120 results on '"PHASE-III TRIAL"'
Search Results
2. Safety, immunogenicity, and lot-to-lot consistency of a multidose Sabin strain-based inactivated polio vaccine: a phase III, randomized, blinded, positive-control clinical trial in infants aged 2 months
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Guangwei Feng, Deyu Jiang, Weixiao Han, Zhiqiang Xie, Zhiwei Jiang, Lili Huang, Jianfeng Wang, Wei Zhang, Li Xu, Jiebing Tan, Wangyang You, Guoliang Cui, Changgui Li, and Yanxia Wang
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Sabin strain ,Inactivated poliovirus vaccine ,Lot-to-lot consistency ,Phase-III trial ,Infectious and parasitic diseases ,RC109-216 - Abstract
ABSTRACT: Objectives: To evaluate the safety, immunogenicity, and lot-to-lot consistency of Sabin strain-based inactivated polio vaccine (sIPV) in a five-dose vial presentation. Methods: Stage I was an open-label safety observation, in which 72 healthy subjects (including 24 adults, children, and infants each) were given one or three doses of the five-dose vial sIPV; stage II was a randomized, blinded, and positive-control study, in which 1500 infants were randomized at the ratio of 1: 1: 1: 1: 1 into five groups to receive either three doses of the five-dose sIPV three lots, a conventional inactivated poliovirus vaccine, or a single-dose sIPV as controls, for primary immunization. Safety, immunogenicity, and lot-to-lot consistency were assessed. Results: Among 1456 subjects who completed the primary immunization, the geometric mean titer ratios of types 1, 2, and 3 of each pair of lots were all within the equivalence criteria margin (0.67-1.50). The seroconversion rates of types 1, 2, and 3 in the combined test group were 98.02%, 94.07%, and 98.77%, respectively, which were noninferior to both control groups. The overall incidence of adverse reactions was 29.68% and erythema was the most common adverse reaction with incidences of 10.47%,9.33%, and 9.73% in the combined test group and control groups (P >0.05). Conclusion: The five-dose sIPV demonstrated good safety, immunogenicity, and lot-to-lot consistency.
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- 2023
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3. Safety, immunogenicity, and lot-to-lot consistency of a multidose Sabin strain-based inactivated polio vaccine: a phase III, randomized, blinded, positive-control clinical trial in infants aged 2 months.
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Feng, Guangwei, Jiang, Deyu, Han, Weixiao, Xie, Zhiqiang, Jiang, Zhiwei, Huang, Lili, Wang, Jianfeng, Zhang, Wei, Xu, Li, Tan, Jiebing, You, Wangyang, Cui, Guoliang, Li, Changgui, and Wang, Yanxia
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POLIOMYELITIS vaccines , *IMMUNE response , *INFANTS , *CLINICAL trials , *HIV seroconversion , *NEONATAL sepsis , *POLIOVIRUS - Abstract
• The multidose Sabin strain-based inactivated polio vaccine (sIPV) showed good lot-to-lot consistency in immunogenicity. • The multidose sIPV met the noninferiority criteria of immunogenicity. • The multidose sIPV demonstrated a favorable safety profile. • No vaccine-related serious adverse events occurred. To evaluate the safety, immunogenicity, and lot-to-lot consistency of Sabin strain-based inactivated polio vaccine (sIPV) in a five-dose vial presentation. Stage I was an open-label safety observation, in which 72 healthy subjects (including 24 adults, children, and infants each) were given one or three doses of the five-dose vial sIPV; stage II was a randomized, blinded, and positive-control study, in which 1500 infants were randomized at the ratio of 1: 1: 1: 1: 1 into five groups to receive either three doses of the five-dose sIPV three lots, a conventional inactivated poliovirus vaccine, or a single-dose sIPV as controls, for primary immunization. Safety, immunogenicity, and lot-to-lot consistency were assessed. Among 1456 subjects who completed the primary immunization, the geometric mean titer ratios of types 1, 2, and 3 of each pair of lots were all within the equivalence criteria margin (0.67-1.50). The seroconversion rates of types 1, 2, and 3 in the combined test group were 98.02%, 94.07%, and 98.77%, respectively, which were noninferior to both control groups. The overall incidence of adverse reactions was 29.68% and erythema was the most common adverse reaction with incidences of 10.47%,9.33%, and 9.73% in the combined test group and control groups (P >0.05). The five-dose sIPV demonstrated good safety, immunogenicity, and lot-to-lot consistency. [ABSTRACT FROM AUTHOR]
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- 2023
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4. A comparison between phase-III trials and a phase-IV study of nalmefene in alcohol use disorder patients. Is there a difference?
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BARRIO, PABLO, ORTEGA, LLUISA, GUARDIA, JOSEP, RONCERO, CARLOS, YUGUERO, LARA, and GUAL, ANTONI
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ALCOHOLISM ,UNIVARIATE analysis - Abstract
Copyright of Adicciones is the property of Sociedad Cientifica Espanola de Estudios sobre el Alcohol and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2019
5. Real-world evidence of adjuvant gemcitabine plus capecitabine vs gemcitabine monotherapy for pancreatic ductal adenocarcinoma
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Jong, E.J.M. de, Janssen, Q.P., Simons, T.F.A., Besselink, M.G., Bonsing, B.A., Bouwense, S.A.W., Geurts, S.M.E., Homs, M.Y.V., Meijer, V.E. de, Tjan-Heijnen, V.C.G., Laarhoven, H.W.M. van, Valkenburg-van Iersel, L.B.J., Wilmink, J.W., Geest, L.G. van der, Koerkamp, B.G., Vos-Geelen, J. de, Dutch Pancreatic Canc Grp, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Interne Geneeskunde, MUMC+: MA Heelkunde (9), MUMC+: MA Medische Oncologie (9), Medical Oncology, Surgery, CCA - Cancer Treatment and Quality of Life, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Oncology, Center for Liver, Digestive and Metabolic Diseases (CLDM), Groningen Institute for Organ Transplantation (GIOT), Internal medicine, and VU University medical center
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Cancer Research ,RESECTION ,endocrine system diseases ,pancreatic cancer ,MULTICENTER ,PHASE-III TRIAL ,CHEMOTHERAPY ,OPEN-LABEL ,Deoxycytidine ,Gemcitabine ,CANCER ,THERAPY ,TRENDS ,Pancreatic Neoplasms ,FOLFIRINOX ,Oncology ,SDG 3 - Good Health and Well-being ,Chemotherapy, Adjuvant ,Antineoplastic Combined Chemotherapy Protocols ,SURVIVAL ,Humans ,Capecitabine ,Carcinoma, Pancreatic Ductal - Abstract
The added value of capecitabine to adjuvant gemcitabine monotherapy (GEM) in pancreatic ductal adenocarcinoma (PDAC) was shown by the ESPAC-4 trial. Real-world data on the effectiveness of gemcitabine plus capecitabine (GEMCAP), in patients ineligible for mFOLFIRINOX, are lacking. Our study assessed whether adjuvant GEMCAP is superior to GEM in a nationwide cohort. Patients treated with adjuvant GEMCAP or GEM after resection of PDAC without preoperative treatment were identified from The Netherlands Cancer Registry (2015-2019). The primary outcome was overall survival (OS), measured from start of chemotherapy. The treatment effect of GEMCAP vs GEM was adjusted for sex, age, performance status, tumor size, lymph node involvement, resection margin and tumor differentiation in a multivariable Cox regression analysis. Secondary outcome was the percentage of patients who completed the planned six adjuvant treatment cycles. Overall, 778 patients were included, of whom 21.1% received GEMCAP and 78.9% received GEM. The median OS was 31.4 months (95% CI 26.8-40.7) for GEMCAP and 22.1 months (95% CI 20.6-25.0) for GEM (HR: 0.71, 95% CI 0.56-0.90; logrank P = .004). After adjustment for prognostic factors, survival remained superior for patients treated with GEMCAP (HR: 0.73, 95% CI 0.57-0.92, logrank P = .009). Survival with GEMCAP was superior to GEM in most subgroups of prognostic factors. Adjuvant chemotherapy was completed in 69.5% of the patients treated with GEMCAP and 62.7% with GEM (P = .11). In this nationwide cohort of patients with PDAC, adjuvant GEMCAP was associated with superior survival as compared to GEM monotherapy and number of cycles was similar.
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- 2022
6. The risk of radiation-induced neurocognitive impairment and the impact of sparing the hippocampus during pediatric proton cranial irradiation
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Daniel Gram, N. Patrik Brodin, Thomas Björk-Eriksson, Karsten Nysom, and Per Munck af Rosenschöld
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AVOIDANCE ,PHASE-III TRIAL ,Hematology ,General Medicine ,hippocampal avoidance ,ONCOLOGY ,Neurocognitive impairment ,THERAPY ,TUMORS ,tumor control probability ,NEUROGENESIS ,DELINEATION ,CRANIOSPINAL IRRADIATION ,Oncology ,MEDULLOBLASTOMA ,normal tissue complication probability ,pediatric hippocampus ,Radiology, Nuclear Medicine and imaging ,WHOLE-BRAIN RADIOTHERAPY - Abstract
Background and purposeHippocampus is a central component for neurocognitive function and memory. We investigated the predicted risk of neurocognitive impairment of craniospinal irradiation (CSI) and the deliverability and effects of hippocampal sparing. The risk estimates were derived from published NTCP models. Specifically, we leveraged the estimated benefit of reduced neurocognitive impairment with the risk of reduced tumor control.Material and methodsFor this dose planning study, a total of 504 hippocampal sparing intensity modulated proton therapy (HS-IMPT) plans were generated for 24 pediatric patients whom had previously received CSI. Plans were evaluated with respect to target coverage and homogeneity index to target volumes, maximum and mean dose to OARs. Paired t-tests were used to compare hippocampal mean doses and normal tissue complication probability estimates.ResultsThe median mean dose to the hippocampus could be reduced from 31.3 Gy(RBE) to 7.3 Gy(RBE) (p < .001), though 20% of these plans were not considered clinically acceptable as they failed one or more acceptance criterion. Reducing the median mean hippocampus dose to 10.6 Gy(RBE) was possible with all plans considered as clinically acceptable treatment plans. By sparing the hippocampus to the lowest dose level, the risk estimation of neurocognitive impairment could be reduced from 89.6%, 62.1% and 51.1% to 41.0% (p < .001), 20.1% (p < .001) and 29.9% (p < .001) for task efficiency, organization and memory, respectively. Estimated tumor control probability was not adversely affected by HS-IMPT, ranging from 78.5 to 80.5% for all plans.ConclusionsWe present estimates of potential clinical benefit in terms of neurocognitive impairment and demonstrate the possibility of considerably reducing neurocognitive adverse effects, minimally compromising target coverage locally using HS-IMPT.
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- 2023
7. Safety of pre- or postoperative accelerated radiotherapy in 5 fractions: A randomized pilot trial
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Vincent Vakaet, Hans Van Hulle, Koen Van de Vijver, Ingeborg Hilderson, Eline Naert, Wilfried De Neve, Jo Vandorpe, An Hendrix, Menekse Göker, Herman Depypere, Glenn Vergauwen, Rudy Van den Broecke, Pieter De Visschere, Geert Braems, Katrien Vandecasteele, Hannelore Denys, and Liv Veldeman
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Neo-adjuvant radiotherapy ,PREOPERATIVE IRRADIATION ,Breast Neoplasms ,Pilot Projects ,Mastectomy, Segmental ,Accelerated radiotherapy ,NEOADJUVANT CHEMOTHERAPY ,Breast cancer ,NONINFLAMMATORY BREAST-CANCER ,QUALITY-OF-LIFE ,RADIATION-THERAPY ,ACUTE TOXICITY ,Medicine and Health Sciences ,Humans ,RC254-282 ,Retrospective Studies ,CONSERVATIVE SURGERY ,CONCURRENT ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,PHASE-III TRIAL ,Feasibility ,General Medicine ,Simultaneously integrated boost ,Chemotherapy, Adjuvant ,SURVIVAL ,Surgery ,Original Article ,Female ,Radiotherapy, Adjuvant ,Overall treatment time - Abstract
Objective Neo-adjuvant radiotherapy (NART) for breast cancer has shown promising survival results in retrospective trials. However, there are some obstacles such as a chemotherapy delay, an increased overall treatment time (OTT) and the risk of increasing surgical morbidity. Accelerated radiotherapy (RT) in 5 fractions allows to deliver NART in a very short time span and minimizes the delay of surgery and chemotherapy. This trial investigates this NART schedule for safety, feasibility and OTT. Material and methods Twenty patients eligible for neo-adjuvant chemotherapy (NACT) and breast conserving surgery, were randomized between NART before NACT or NACT and postoperative RT. In both arms, RT treatment was given in 5 fractions to the whole breast with a simultaneously integrated boost (SIB) on the tumor(bed). Lymph node irradiation was given concomitantly in case of lymph node involvement. OTT was defined as the time from diagnosis to last surgery in the intervention group, while in the control group the time between diagnosis and last RT-fraction was used. In the intervention group NACT-delay was defined as time between diagnosis and start of chemotherapy. Results 20 patients were included, and 19 patients completed treatment. OTT was significantly shorter in the intervention group (mean 218 days, range 196–253) compared to the control group (mean 237, range 211–268, p = 0.001). The difference in mean duration from diagnosis to the first treatment was a non-significant 4 days longer (31 vs 27 days, p = 0.28), but the start of NACT after diagnosis was delayed by 21 days (48 vs 27 days, p, Highlights • Neo-adjuvant radiotherapy in 5 fractions with simultaneous integrated boost is feasible. • Overall treatment time is not increased with neo-adjuvant radiotherapy. • Initiation of chemotherapy is delayed by 21 days with neo-adjuvant radiotherapy.
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- 2022
8. Molecular classification of endometrial carcinoma : a clinically oriented review
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Loukovaara, Mikko, Pasanen, Annukka, Bützow, Ralf, University of Helsinki, Clinicum, Department of Obstetrics and Gynecology, HUS Gynecology and Obstetrics, HUSLAB, Department of Pathology, Medicum, ATG - Applied Tumor Genomics, Faculty of Medicine, and Helsinki University Hospital Area
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uterus ,PHASE-III TRIAL ,DIABETES-MELLITUS ,HIGH-INTERMEDIATE ,carcinoma ,OPEN-LABEL ,CANCER ,BODY-MASS INDEX ,EXTERNAL-BEAM RADIOTHERAPY ,VAGINAL BRACHYTHERAPY ,CELL-ADHESION MOLECULE ,3111 Biomedicine ,endometrium ,PELVIC RADIATION-THERAPY - Abstract
The Cancer Genome Atlas research network performed a genome-wide analysis of endometrial carcinomas in 2013 and classified tumours into four distinct subgroups: polymerase-epsilon ultramutated, microsatellite unstable hypermutated, copy-number low and copy-number high. These molecular alterations are mostly mutually exclusive as only about 3% of tumours exhibit more than one molecular signature. Apart from the polymerase-epsilon ultramutated subgroup, molecular classification can be reproduced by using surrogate markers. This has facilitated the implementation of molecular diagnostics into routine patient care. Molecular subgroups are associated with different prognoses; thus, improved risk assessment is their most obvious clinical application. However, based on their unique molecular architectures, molecular subgroups should not be regarded simply as risk groups but rather as distinct diseases. This has prompted us and others to examine the role of molecular subgroups in modifying the prognostic effect of traditional risk factors, including clinical factors, uterine factors and tissue biomarkers, and in predicting the response to adjuvant therapies. In the following review, we summarise the current knowledge of molecularly classified endometrial carcinoma and present, based on our own experience, a proposal for implementing molecular classification into daily practice in pathology laboratories.
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- 2022
9. Adjuvant capecitabine-containing chemotherapy benefit and homologous recombination deficiency in early-stage triple-negative breast cancer patients
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Leonora W. de Boo, Katarzyna Jóźwiak, Heikki Joensuu, Henrik Lindman, Susanna Lauttia, Mark Opdam, Charlaine van Steenis, Wim Brugman, Roelof J. C. Kluin, Philip C. Schouten, Marleen Kok, Petra M. Nederlof, Michael Hauptmann, Sabine C. Linn, Heikki Joensuu / Principal Investigator, HUS Comprehensive Cancer Center, Department of Oncology, University of Helsinki, Department of Pathology, and HUSLAB
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Cancer Research ,BRCANESS ,3122 Cancers ,EPIRUBICIN ,Breast Neoplasms ,Triple Negative Breast Neoplasms ,SECONDARY MUTATIONS ,Disease-Free Survival ,NEOADJUVANT CHEMOTHERAPY ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,BRCA1-LIKE PROFILE ,Homologous Recombination ,skin and connective tissue diseases ,Cyclophosphamide ,Capecitabine ,DOCETAXEL ,Cancer och onkologi ,PLATINUM-BASED CHEMOTHERAPY ,CLINICAL-FEATURES ,PHASE-III TRIAL ,Oncology ,Chemotherapy, Adjuvant ,Cancer and Oncology ,5-FLUOROURACIL ,Female - Abstract
BackgroundThe addition of adjuvant capecitabine to standard chemotherapy of early-stage triple-negative breast cancer (TNBC) patients has improved survival in a few randomised trials and in meta-analyses. However, many patients did not benefit. We evaluated theBRCA1-like DNA copy number signature, indicative of homologous recombination deficiency, as a predictive biomarker for capecitabine benefit in the TNBC subgroup of the FinXX trial.MethodsEarly-stage TNBC patients were randomised between adjuvant capecitabine-containing (TX + CEX: capecitabine-docetaxel, followed by cyclophosphamide-epirubicin-capecitabine) and conventional chemotherapy (T + CEF: docetaxel, followed by cyclophosphamide-epirubicin-fluorouracil). TumourBRCA1-like status was determined on low-coverage, whole genome next-generation sequencing data using an established DNA comparative genomic hybridisation algorithm.ResultsFor 129/202 (63.9%) patients theBRCA1-like status could be determined, mostly due to lack of tissue. During a median follow-up of 10.7 years, 35 recurrences and 32 deaths occurred. Addition of capecitabine appears to improve recurrence-free survival more among 61 (47.3%) patients with non-BRCA1-like tumours (HR 0.23, 95% CI 0.08–0.70) compared to 68 (52.7%) patients withBRCA1-like tumours (HR 0.66, 95% CI 0.24–1.81) (P-interaction = 0.17).ConclusionBased on our data, patients with non-BRCA1-like TNBC appear to benefit from the addition of capecitabine to adjuvant chemotherapy. Patients withBRCA1-like TNBC may also benefit. Additional research is needed to define the subgroup withinBRCA1-like TNBC patients who may not benefit from adjuvant capecitabine.
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- 2022
10. Survival outcomes of women with grade 3 endometrioid endometrial cancer: the impact of adjuvant treatment strategies
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Mehmet Ali Vardar, Ali Ayhan, Kemal Güngördük, Taylan Şenol, Nurettin Boran, Taner Turan, Nuri Yildirim, Salih Taşkın, Osman Aşıcıoğlu, Ümran Küçükgöz Güleç, Hanifi Şahin, Varol Gülseren, Mustafa Zelal Muallem, Andrea Miranda, Mehmet Mutlu Meydanli, Jumana Muallem, Jalid Sehouli, A. Özdemir, Ghanim Khatib, and Tufan Oge
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Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Endometrial adenocarcinoma ,Phase-Iii Trial ,Carcinomas ,Disease-Free Survival ,Internal medicine ,medicine ,Humans ,Stage (cooking) ,Grade 3 ,Neoplasm Staging ,Retrospective Studies ,Early-Stage ,Hysterectomy ,business.industry ,Endometrial cancer ,Obstetrics and Gynecology ,Lymphadenectomy ,General Medicine ,medicine.disease ,Prognosis ,Endometrial Neoplasms ,stomatognathic diseases ,Cohort ,Treatment strategy ,Population study ,Lymph Node Excision ,Female ,business ,Adjuvant ,Carcinoma, Endometrioid - Abstract
© 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.Aim: This multicenter investigation was performed to evaluate the adjuvant treatment options, prognostic factors, and patterns of recurrence in patients with grade 3 endometrioid endometrial cancer (G3-EEC). Materials and methods: The medical reports of patients undergoing at least total hysterectomy and salpingo-oophorectomy for G3-EEC between 1996 and 2018 at 11 gynecological oncology centers were analyzed. Optimal surgery was defined as removal of all disease except for residual nodules with a maximum diameter ≤ 1 cm, as determined at completion of the primary operation. Adequate systematic lymphadenectomy was defined as the removal of at least 15 pelvic and at least 5 paraaortic LNs. Results: The study population consists of 465 women with G3-EEC. The 5-year disease-free survival (DFS) and overall survival (OS) rates of the entire cohort are 50.3% and 57.6%, respectively. Adequate systematic lymphadenectomy was achieved in 429 (92.2%) patients. Optimal surgery was achieved in 135 (75.0%) patients in advanced stage. Inadequate lymphadenectomy (DFS; HR 3.4, 95% CI 3.0–5.6; P = 0.016—OS; HR 3.2, 95% CI 1.6–6.5; P = 0.019) was independent prognostic factors for 5-year DFS and OS. Conclusion: Inadequate lymphadenectomy and LVSI were independent prognostic factors for worse DFS and OS in women with stage I–II G3-EEC. Adequate lymphadenectomy and optimal surgery were independent prognostic factors for better DFS and OS in women with stage III–IV G3-EEC.
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- 2022
11. The Increasing Prognostic and Predictive Roles of the Tumor Primary Chemosensitivity Assessed by CA-125 Elimination Rate Constant K (KELIM) in Ovarian Cancer
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EPITHELIAL OVARIAN ,primary chemosensitivity ,CARBOPLATIN ,KELIM ,PHASE-III TRIAL ,treatment success ,RANDOMIZED CLINICAL-TRIAL ,NEOADJUVANT CHEMOTHERAPY ,1ST-LINE TREATMENT ,FALLOPIAN-TUBE ,ovarian cancer ,CA-125 ,PRIMARY SURGERY ,EXPLORATORY ANALYSIS ,PROGRESSION-FREE SURVIVAL - Abstract
Ovarian cancer is the gynecological cancer with the worst prognosis and the highest mortality rate because 75% of patients are diagnosed with advanced stage III-IV disease. About 50% of patients are now treated with neoadjuvant chemotherapy followed by interval debulking surgery (IDS). In that context, there is a need for accurate predictors of tumor primary chemosensitivity, as it may impact the feasibility of subsequent IDS. Across seven studies with more than 12,000 patients, including six large randomized clinical trials and a national cancer registry, along with a mega-analysis database with 5842 patients, the modeled CA-125 ELIMination rate constant K (KELIM), the calculation of which is based on the longitudinal kinetics during the first three cycles of platinum-based chemotherapy, was shown to be a reproducible indicator of tumor intrinsic chemosensitivity. Indeed, KELIM is strongly associated with the likelihood of complete IDS, subsequent platinum-free interval, progression-free survival, and overall survival, along with the efficacy of maintenance treatment with bevacizumab or veliparib. As a consequence, KELIM might be used to guide more subtly the medical and surgical treatments in a first-line setting. Moreover, it could be used to identify the patients with poorly chemosensitive disease, who will be the best candidates for innovative treatments meant to reverse the chemoresistance, such as cell cycle inhibitors or immunotherapy.
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- 2022
12. Gastric cancer
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RANDOMIZED CLINICAL-TRIAL ,LYMPH-NODE DISSECTION ,ENDOSCOPIC SUBMUCOSAL DISSECTION ,GASTROESOPHAGEAL JUNCTION ,MICROSATELLITE INSTABILITY ,QUALITY-OF-LIFE ,PERIOPERATIVE CHEMOTHERAPY ,SUPPORTIVE CARE ,WHOLE-SLIDE IMAGES ,PHASE-III TRIAL ,PYLORUS-PRESERVING GASTRECTOMY - Abstract
Gastric cancer is the fifth most common cancer and the third most common cause of cancer death globally. Risk factors for the condition include Helicobacter pylori infection, age, high salt intake, and diets low in fruit and vegetables. Gastric cancer is diagnosed histologically after endoscopic biopsy and staged using CT, endoscopic ultrasound, PET, and laparoscopy. It is a molecularly and phenotypically highly heterogeneous disease. The main treatment for early gastric cancer is endoscopic resection. Non-early operable gastric cancer is treated with surgery, which should include D2 lymphadenectomy (including lymph node stations in the perigastric mesentery and along the celiac arterial branches). Perioperative or adjuvant chemotherapy improves survival in patients with stage 1B or higher cancers. Advanced gastric cancer is treated with sequential lines of chemotherapy, starting with a platinum and fluoropyrimidine doublet in the first line; median survival is less than 1 year. Targeted therapies licensed to treat gastric cancer include trastuzumab (HER2-positive patients first line), ramucirumab (anti-angiogenic second line), and nivolumab or pembrolizumab (anti-PD-1 third line).
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- 2020
13. Systematic review of photobiomodulation for the management of oral mucositis in cancer patients and clinical practice guidelines
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Oral complications of cancer therapy ,Low-level laser therapy ,Pain ,LOW-LEVEL LASER ,Guidelines ,Photobiostimulation ,Oral mucositis ,Laser therapy ,QUALITY-OF-LIFE ,Chemotherapy ,Cancer ,Stomatitis ,HE-NE-LASER ,Radiotherapy ,RADIATION-INDUCED MUCOSITIS ,PEDIATRIC-PATIENTS ,LLLT ,Prevention ,LED ,ECONOMIC OUTCOMES ,STEM-CELL TRANSPLANTATION ,PHASE-III TRIAL ,Photobiomodulation ,LOW-POWER LASER ,Treatment ,LOW-ENERGY LASER ,Evidence-based - Abstract
Purpose To systematically review the literature and update the evidence-based clinical practice guidelines for the use of photobiomodulation (PBM), such as laser and other light therapies, for the prevention and/or treatment of oral mucositis (OM). Methods A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO) using PubMed and Web of Science. We followed the MASCC methods for systematic review and guidelines development. The rigorously evaluated evidence for each intervention, in each cancer treatment setting, was assigned a level-of-evidence (LoE). Based on the LoE, one of the following guidelines was determined: Recommendation, Suggestion, or No Guideline Possible. Results Recommendations are made for the prevention of OM and related pain with PBM therapy in cancer patients treated with one of the following modalities: hematopoietic stem cell transplantation, head and neck (H&N) radiotherapy (without chemotherapy), and H&N radiotherapy with chemotherapy. For each of these modalities, we recommend 1-2 clinically effective protocols; the clinician should adhere to all parameters of the protocol selected. Due to inadequate evidence, currently, No Guideline Possible for treatment of established OM or for management of chemotherapy-related OM. The reported clinical settings were extremely variable, limiting data integration. Conclusions The evidence supports the use of specific settings of PBM therapy for the prevention of OM in specific patient populations. Under these circumstances, PBM is recommended for the prevention of OM. The guidelines are subject to continuous update based on new published data.
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- 2019
14. Risk Stratification of Endometrial Cancer Patients: FIGO Stage, Biomarkers and Molecular Classification
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molecular classification ,LYMPH-NODE METASTASIS ,PHASE-III TRIAL ,HIGH-INTERMEDIATE ,FIGO stage ,TCGA ,surgical staging ,CIRCULATING TUMOR-CELLS ,uterine neoplasm ,INTEROBSERVER VARIABILITY ,ADJUVANT CHEMOTHERAPY ,ASTEC TRIAL ,TRANSPORTEC ,endometrial cancer ,PROGNOSTIC-SIGNIFICANCE ,PERITONEAL CYTOLOGY ,ProMisE ,PROSPECTIVE MULTICENTER - Abstract
Simple Summary: Endometrial cancer (EC) is the most common gynaecologic malignancy in developed countries. Most patients are sufficiently treated with removal of uterus, tubes and ovaries. It depends on the estimated risk of metastases at diagnosis if more extensive surgery (removal of lymph nodes, peritoneum and/or omentum), to detect small metastases, is indicated. Metastases are associated with a higher risk of recurrence and justify adjuvant treatment (i.e., radiotherapy and/or chemotherapy). Recently it is advised to also subdivide EC into four molecular subgroups. Each subgroup is highly associated to a certain risk of recurrence and helps to decide for adjuvant treatment. What surgery should be performed in each of the subgroups is currently unknown. Moreover, it is uncertain if integration of other factors into the molecular classification could help to improve the risk classification. This review summarizes different aspects of surgery. Moreover, the relation between metastases and other factors including molecular classification are evaluated.Endometrial cancer (EC) is the most common gynaecologic malignancy in developed countries. The main challenge in EC management is to correctly estimate the risk of metastases at diagnosis and the risk to develop recurrences in the future. Risk stratification determines the need for surgical staging and adjuvant treatment. Detection of occult, microscopic metastases upstages patients, provides important prognostic information and guides adjuvant treatment. The molecular classification subdivides EC into four prognostic subgroups: POLE ultramutated; mismatch repair deficient (MMRd); nonspecific molecular profile (NSMP); and TP53 mutated (p53abn). How surgical staging should be adjusted based on preoperative molecular profiling is currently unknown. Moreover, little is known whether and how other known prognostic biomarkers affect prognosis prediction independent of or in addition to these molecular subgroups. This review summarizes the factors incorporated in surgical staging (i.e., peritoneal washing, lymph node dissection, omentectomy and peritoneal biopsies), and its impact on prognosis and adjuvant treatment decisions in an era of molecular classification of EC. Moreover, the relation between FIGO stage and molecular classification is evaluated including the current gaps in knowledge and future perspectives.
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- 2021
15. Cancer of the corpus uteri: 2021 update
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Martin Koskas, Mansoor Raza Mirza, Carien L. Creutzberg, Frédéric Amant, Obstetrics and Gynaecology, CCA - Cancer Treatment and Quality of Life, and ARD - Amsterdam Reproduction and Development
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Oncology ,INTERMEDIATE-RISK ,medicine.medical_treatment ,chemotherapy ,surgery ,QUALITY-OF-LIFE ,FIGO Cancer Report ,Standard treatment ,Obstetrics & Gynecology ,Obstetrics and Gynecology ,PHASE-III TRIAL ,General Medicine ,RISK ENDOMETRIAL CANCER ,STAGE-I ,Chemotherapy, Adjuvant ,endometrial cancer ,Female ,gynecologic cancer ,Life Sciences & Biomedicine ,PELVIC RADIATION-THERAPY ,medicine.medical_specialty ,Hysterectomy ,Internal medicine ,medicine ,Adjuvant therapy ,ROUTINE FOLLOW-UP ,Humans ,radiotherapy ,Neoplasm Staging ,Retrospective Studies ,Science & Technology ,corpus uteri ,Performance status ,business.industry ,Endometrial cancer ,Uterus ,LYMPH-NODE METASTASIS ,LONG-TERM SURVIVAL ,Cancer ,medicine.disease ,Endometrial Neoplasms ,Radiation therapy ,EXTERNAL-BEAM RADIOTHERAPY ,Lymph Node Excision ,Radiotherapy, Adjuvant ,Lymphadenectomy ,Neoplasm Recurrence, Local ,business - Abstract
Endometrial cancer is the most common gynecological malignancy in high- and middle-income countries. Although the overall prognosis is relatively good, high-grade endometrial cancers have a tendency to recur. Recurrence needs to be prevented since the prognosis for recurrent endometrial cancer is dismal. Treatment tailored to tumor biology is the optimal strategy to balance treatment efficacy against toxicity. Since The Cancer Genome Atlas defined four molecular subgroups of endometrial cancers, the molecular factors are increasingly used to define prognosis and treatment. Standard treatment consists of hysterectomy and bilateral salpingo-oophorectomy. Lymphadenectomy (and increasingly sentinel node biopsy) enables identification of lymph node-positive patients who need adjuvant treatment, including radiotherapy and chemotherapy. Adjuvant therapy is used for Stage I-II patients with high-risk factors and Stage III patients; chemotherapy is especially used in non-endometrioid cancers and those in the copy-number high molecular group characterized by TP53 mutation. In advanced disease, a combination of surgery to no residual disease and chemotherapy with or without radiotherapy results in the best outcome. Surgery for recurrent disease is only advocated in patients with a good performance status with a relatively long disease-free interval. ispartof: INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS vol:155 issue:Suppl 1 pages:45-60 ispartof: location:United States status: published
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- 2021
16. A Replication stress biomarker is associated with response to gemcitabine versus combined gemcitabine and ATR inhibitor therapy in ovarian cancer
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Madeline Polak, Joyce F. Liu, Andrea E. Wahner Hendrickson, Elise C. Kohn, Ursula A. Matulonis, Geoffrey I. Shapiro, Panagiotis A. Konstantinopoulos, Nabihah Tayob, Bose Kochupurakkal, Alan D. D'Andrea, Elizabeth K. Lee, Su Chun Cheng, Doga Gulhan, David L. Kolin, Anniina Färkkilä, Dipanjan Chowdhury, Elizabeth H. Stover, Jennifer Curtis, Alexandre André B.A. da Costa, Research Program in Systems Oncology, Department of Obstetrics and Gynecology, and HUS Gynecology and Obstetrics
- Subjects
Oncology ,Exacerbation ,medicine.medical_treatment ,General Physics and Astronomy ,Phases of clinical research ,Ataxia Telangiectasia Mutated Proteins ,Deoxycytidine ,0302 clinical medicine ,3123 Gynaecology and paediatrics ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,CLINICAL ASSAYS ,Ovarian Neoplasms ,0303 health sciences ,Multidisciplinary ,Molecular medicine ,PHASE-III TRIAL ,CHEMOTHERAPY ,Progression-Free Survival ,PEGYLATED LIPOSOMAL DOXORUBICIN ,3. Good health ,Retinoblastoma Binding Proteins ,030220 oncology & carcinogenesis ,Pyrazines ,Biomarker (medicine) ,Female ,medicine.drug ,DNA Replication ,medicine.medical_specialty ,Science ,3122 Cancers ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Ovarian cancer ,Internal medicine ,Biomarkers, Tumor ,Humans ,Progression-free survival ,Protein Kinase Inhibitors ,SIGNATURES ,030304 developmental biology ,Chemotherapy ,business.industry ,Recombinational DNA Repair ,General Chemistry ,Isoxazoles ,Oncogenes ,medicine.disease ,Gemcitabine ,Genomic Biomarker ,DNA-DAMAGE ,Mutation ,CELLS ,3111 Biomedicine ,business - Abstract
In a trial of patients with high grade serous ovarian cancer (HGSOC), addition of the ATR inhibitor berzosertib to gemcitabine improved progression free survival (PFS) compared to gemcitabine alone but biomarkers predictive of treatment are lacking. Here we report a candidate biomarker of response to gemcitabine versus combined gemcitabine and ATR inhibitor therapy in HGSOC ovarian cancer. Patients with replication stress (RS)-high tumors (n = 27), defined as harboring at least one genomic RS alteration related to loss of RB pathway regulation and/or oncogene-induced replication stress achieve significantly prolonged PFS (HR = 0.38, 90% CI, 0.17–0.86) on gemcitabine monotherapy compared to those with tumors without such alterations (defined as RS-low, n = 30). However, addition of berzosertib to gemcitabine benefits only patients with RS-low tumors (gemcitabine/berzosertib HR 0.34, 90% CI, 0.13–0.86) and not patients with RS-high tumors (HR 1.11, 90% CI, 0.47–2.62). Our findings support the notion that the exacerbation of RS by gemcitabine monotherapy is adequate for lethality in RS-high tumors. Conversely, for RS-low tumors addition of berzosertib-mediated ATR inhibition to gemcitabine is necessary for lethality to occur. Independent prospective validation of this biomarker is required., A randomized phase 2 study recently showed that the addition of ATR inhibitor berzosertib to gemcitabine improved PFS compared to gemcitabine alone in patients with ovarian cancer. In this preplanned exploratory study, the authors demonstrate that a genomic biomarker of replication-stress is associated with outcome to gemcitabine alone and may predict which patients benefit from addition of the ATR inhibitor berzosertib.
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- 2021
17. Anthracyclines Strike Back: Rediscovering Non-Pegylated Liposomal Doxorubicin in Current Therapeutic Scenarios of Breast Cancer
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Javier Cortes, Mariavittoria Locci, Daniele Generali, Diana Lüftner, Sergio Venturini, Lucia Del Mastro, Nadia Harbeck, Matteo Lambertini, Guy Jerusalem, Concetta Elisa Onesti, Francesco Schettini, Alessandra Gennari, Miguel Martin, Vivianne C. G. Tjan-Heijnen, Mario Giuliano, Rupert Bartsch, Giorgio Mustacchi, David J. Pinato, Khalil Zaman, Ahmad Awada, Sylvie Rottey, Mario Campone, Sabino De Placido, Ida Paris, Peter van Dam, Joseph Gligorov, Hans Wildiers, Giuseppe Curigliano, Institut Català de la Salut, [Schettini F] Translational Genomics and Targeted Therapies in Solid Tumors Research Group, Barcelona, Spain. Department of Medical Oncology, Hospital Clinic of Barcelona, Barcelona, Spain. [Giuliano M] Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy. [Lambertini M] Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy. Department of Medical Oncology, U.O.C Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy. [Bartsch R] Division of Oncology, Department of Medicine 1, Medical University of Vienna, Vienna, Austria. [Pinato DJ] Division of Cancer, Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, UK. Department of Translational Medicine, Università del Piemonte Orientale 'A. Avogadro', Novara, Italy. [Onesti CE] Clinical and Oncological Research Department, IRCCS Regina Elena National Cancer Institute, Rome, Italy. [Cortes J] Oncology Department, IOB Institute of Oncology, Quiron Group, 08023 Madrid, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Schettini, Francesco, Giuliano, Mario, Lambertini, Matteo, Bartsch, Rupert, Pinato, David Jame, Onesti, Concetta Elisa, Harbeck, Nadia, Lüftner, Diana, Rottey, Sylvie, van Dam, Peter A, Zaman, Khalil, Mustacchi, Giorgio, Gligorov, Joseph, Awada, Ahmad, Campone, Mario, Wildiers, Han, Gennari, Alessandra, Tjan-Heijnen, Vivianne C G, Cortes, Javier, Locci, Mariavittoria, Paris, Ida, Del Mastro, Lucia, De Placido, Sabino, Martín, Miguel, Jerusalem, Guy, Venturini, Sergio, Curigliano, Giuseppe, Generali, Daniele, Schettini, F., Giuliano, M., Lambertini, M., Bartsch, R., Pinato, D. J., Onesti, C. E., Harbeck, N., Luftner, D., Rottey, S., van Dam, P. A., Zaman, K., Mustacchi, G., Gligorov, J., Awada, A., Campone, M., Wildiers, H., Gennari, A., Tjan-heijnen, V. C. G., Cortes, J., Locci, M., Paris, I., Mastro, L. D., De Placido, S., Martin, M., Jerusalem, G., Venturini, S., Curigliano, G., and Generali, D.
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Oncology ,Cancer Research ,medicine.medical_treatment ,Non‐pegylated liposomal doxorubicin ,Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES] ,EPIRUBICIN ,Review ,Anthracycline ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,Oncología ,Breast cancer ,CYCLOPHOSPHAMIDE ,Medicine and Health Sciences ,Endocrinología ,Other subheadings::/therapeutic use [Other subheadings] ,NAB-PACLITAXEL ,RC254-282 ,MULTICENTER TRIAL ,anthracyclines ,neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES] ,PRIMARY ,TRASTUZUMAB PLUS DOCETAXEL ,terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,PHASE-III TRIAL ,Sciences bio-médicales et agricoles ,CHEMOTHERAPY ,metastatic ,Settore SECS-S/01 - STATISTICA ,Metastatic ,Epirubicin ,medicine.drug ,medicine.medical_specialty ,Cyclophosphamide ,Side effect ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,anthracycline ,Hormone receptor ,Quimioteràpia combinada ,triple negative ,Therapeutic index ,breast cancer ,Internal medicine ,Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,CONVENTIONAL DOXORUBICIN ,medicine ,Doxorubicin ,Chemotherapy ,Cardiotoxicity ,business.industry ,PRIMARY CHEMOTHERAPY ,Otros calificadores::/uso terapéutico [Otros calificadores] ,ENCAPSULATED DOXORUBICIN ,hormone receptor ,medicine.disease ,Anthracyclines ,Triple negative ,Cancérologie ,Mama - Càncer - Tractament ,Human medicine ,1ST-LINE THERAPY ,business ,non-pegylated liposomal doxorubicin - Abstract
Anthracyclines are among the most active chemotherapies (CT) in breast cancer (BC). However, cardiotoxicity is a risk and peculiar side effect that has been limiting their use in clinical practice, especially after the introduction of taxanes. Non‐pegylated liposomal doxorubicin (NPLD) has been developed to optimize the toxicity profile induced by anthracyclines, while maintaining its unquestionable therapeutic index, thanks to its delivering characteristics that increase its diffusion in tumor tissues and reduce it in normal tissues. This feature allows NPLD to be safely administered beyond the standard doxorubicin maximum cumulative dose of 450–480 mg/m2. Following three pivotal first‐line phase III trials in HER2‐negative metastatic BC (MBC), this drug was finally approved in combination with cyclophosphamide in this specific setting. Given the increasing complexity of the therapeutic scenario of HER2‐negative MBC, we have carefully revised the most updated literature on the topic and dissected the potential role of NPLD in the evolving therapeutic algorithms., SCOPUS: re.j, info:eu-repo/semantics/published
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- 2021
18. Endometrial Cancer Molecular Characterization
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Daniela Annibali, Regina Esi Mensimah Baiden-Amissah, Sandra Tuyaerts, Frédéric Amant, Clinical sciences, and Medical Oncology
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Cancer Research ,medicine.medical_specialty ,CARCINOMA ,medicine.medical_treatment ,Translational research ,Review ,CLASSIFICATION ,Targeted therapy ,Clinical decision making ,Endometrial cancer ,CARBOPLATIN-PACLITAXEL ,VAGINAL BRACHYTHERAPY ,Obstetrics and Gynaecology ,medicine ,Adjuvant therapy ,RECURRENCE ,Intensive care medicine ,RC254-282 ,Science & Technology ,High risk patients ,genetic alterations ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Cancer ,PHASE-III TRIAL ,HIGH-INTERMEDIATE ,adjuvant therapy ,molecular risk stratification ,medicine.disease ,targeted therapy ,preclinical models ,GRADE ,Oncology ,EXTERNAL-BEAM RADIOTHERAPY ,endometrial cancer ,Risk stratification ,oncology ,business ,Life Sciences & Biomedicine ,PELVIC RADIATION-THERAPY - Abstract
Simple Summary Endometrial carcinomas (EC) have been traditionally classified based on histopathology (types I and II). Determining the risk of a patient to experience disease recurrence is important to decide which patients need adjuvant treatment. The current endometrial carcinoma risk assessment approaches fail to accurately classify patients into low-and high-risk groups. Several studies suggest that combining molecular characteristics with the current risk classification in EC may improve patients’ stratification and treatment decision-making. In this review, we describe how evolving molecular trends can be used as prognostic factors to identify high-risk EC subpopulations. We also look at how the most recent patient-derived models can help researchers find new possible targets and treatments for EC patients. Abstract Endometrial carcinomas (EC) are the sixth most common cancer in women worldwide and the most prevalent in the developed world. ECs have been historically sub-classified in two major groups, type I and type II, based primarily on histopathological characteristics. Notwithstanding the usefulness of such classification in the clinics, until now it failed to adequately stratify patients preoperatively into low- or high-risk groups. Pieces of evidence point to the fact that molecular features could also serve as a base for better patients’ risk stratification and treatment decision-making. The Cancer Genome Atlas (TCGA), back in 2013, redefined EC into four main molecular subgroups. Despite the high hopes that welcomed the possibility to incorporate molecular features into practice, currently they have not been systematically applied in the clinics. Here, we outline how the emerging molecular patterns can be used as prognostic factors together with tumor histopathology and grade, and how they can help to identify high-risk EC subpopulations for better risk stratification and treatment strategy improvement. Considering the importance of the use of preclinical models in translational research, we also discuss how the new patient-derived models can help in identifying novel potential targets and help in treatment decisions.
- Published
- 2021
19. A meta-analysis on salvage surgery as a potentially curative procedure in patients with isolated local recurrent or persistent esophageal cancer after chemoradiotherapy
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RADIATION-THERAPY ,DOSE RADIATION ,Esophageal cancer ,Salvage esophagectomy ,PHASE-III TRIAL ,DECLINED SURGERY ,Definitive chemoradiotherapy ,SQUAMOUS-CELL CARCINOMA ,NEOADJUVANT CHEMORADIOTHERAPY ,CLINICAL-SIGNIFICANCE ,RANDOMIZED-TRIAL ,DEFINITIVE CHEMORADIATION ,RADIOTHERAPY - Abstract
Background: Isolated local recurrent or persistent esophageal cancer (EC) after curative intended definitive (dCRT) or neoadjuvant chemoradiotherapy (nCRT) with initially omitted surgery, is a potential indication for salvage surgery. We aimed to evaluate safety and efficacy of salvage surgery in these patients.Material and methods: A systematic literature search following PRISMA guidelines was performed using databases of PubMed/Medline. All included studies were performed in patients with persistent or recurrent EC after initial treatment with dCRT or nCRT, between 2007 and 2017. Survival analysis was performed with an inverse-variance weighting method.Results: Of the 278 identified studies, 28 were eligible, including a total of 1076 patients. Postoperative complications after salvage esophagectomy were significantly more common among patients with isolated persistent than in those with locoregional recurrent EC, including respiratory (36.6% versus 22.7%; difference in proportion 10.9 with 95% confidence interval (CI) [3.1; 18.7]) and cardiovascular complications (10.4% versus 4.5%; difference in proportion 5.9 with 95% CI [1.5; 10.2]). The pooled estimated 30-and 90-day mortality was 2.6% [1.6; 3.6] and 8.0% [6.3; 9.8], respectively. The pooled estimated 3-year and 5-year overall survival (OS) were 39.0% (95% CI: [35.8; 42.2]) and 19.4% [95% CI:16.5; 22.4], respectively. Patients with isolated persistent or recurrent EC after initial CRT had similar 5-year OS (14.0% versus 19.7%, difference in proportion -5.7, 95% CI [-13.7; 2.3]).Conclusions: Salvage surgery is a potentially curative procedure in patients with locally recurrent or persistent esophageal cancer and can be performed safely after definitive or neoadjuvant chemoradiotherapy when surgery was initially omitted. (C) 2018 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.
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- 2019
20. Nivolumab for Treating Metastatic or Unresectable Urothelial Cancer
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DOCETAXEL ,CARCINOMA ,MONOTHERAPY ,SUPPORTIVE CARE ,MULTICENTER ,PHASE-III TRIAL ,WEEKLY PACLITAXEL ,OPEN-LABEL ,VINFLUNINE PLUS - Abstract
As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer (Bristol-Myers Squibb) of nivolumab (Opdivo (R)) to submit evidence of its clinical and cost effectiveness for metastatic or unresectable urothelial cancer. Kleijnen Systematic Reviews Ltd, in collaboration with Maastricht University Medical Centre+, was commissioned to act as the independent Evidence Review Group (ERG), which produced a detailed review of the evidence for the clinical and cost effectiveness of the technology, based on the company's submission to NICE. Nivolumab was compared with docetaxel, paclitaxel, best supportive care and retreatment with platinum-based chemotherapy (cisplatin plus gemcitabine, but only for patients whose disease has had an adequate response in first-line treatment). Two ongoing, phase I/II, single-arm studies for nivolumab were identified, but no studies directly compared nivolumab with any specified comparator. Evidence from directly examining the single arms of the trial data indicated little difference between the outcomes measured from the nivolumab and comparator studies. A simulated treatment comparison (STC) analysis was used in an attempt to reduce the bias induced by naive comparison, but there was no clear evidence that risk of bias was reduced. Multiple limitations in the STC were identified and remained. The effect of an analysis based on different combinations of covariates in the prediction model remains unknown. The ERG's concerns regarding the economic analysis included the use of a non-established response-based survival analysis method, which introduced additional uncertainty. The use of time-dependent hazard ratios produced overfitting and was not represented in the probabilistic sensitivity analysis. The use of a treatment stopping rule to cap treatment cost left treatment effectiveness unaltered. A relevant comparator was excluded from the base-case analysis. The revised ERG deterministic base-case incremental cost-effectiveness ratios based on the company's Appraisal Consultation Document response were 58,791 pound, 78,869 pound and 62,352 pound per quality-adjusted life-year gained versus paclitaxel, docetaxel and best supportive care, respectively. Nivolumab was dominated by cisplatin plus gemcitabine in the ERG base case. Substantial uncertainties about the relative treatment effectiveness comparing nivolumab against all comparators remained. NICE did not recommend nivolumab, within its marketing authorisation, as an option for treating locally advanced, unresectable or metastatic urothelial carcinoma in adults who have had platinum-containing therapy, and considered that nivolumab was not suitable for use within the Cancer Drugs Fund.
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- 2019
21. Intermittent versus continuous first-line treatment for HER2-negative metastatic breast cancer
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Vivianne C. G. Tjan-Heijnen, Laurence J. C. van Warmerdam, Marta Lopez-Yurda, Edith van Druten, Hiltje de Graaf, Anouk K. M. Claessens, Aafke H. Honkoop, Maurice J.C. van der Sangen, Monique E. M. M. Bos, Jeanette M. Bouma, Jeany M. Rademaker-Lakhai, Frans L. G. Erdkamp, Medical Oncology, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, MUMC+: MA Medische Oncologie (9), and Interne Geneeskunde
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0301 basic medicine ,Oncology ,Cancer Research ,Receptor, ErbB-2 ,medicine.medical_treatment ,THERAPY ,DOUBLE-BLIND ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,Clinical endpoint ,Longitudinal Studies ,Neoplasm Metastasis ,Netherlands ,Scheduling ,PHASE-III TRIAL ,Middle Aged ,CHEMOTHERAPY ,Metastatic breast cancer ,OPEN-LABEL ,Progression-Free Survival ,Bevacizumab ,030220 oncology & carcinogenesis ,SURVIVAL ,Female ,medicine.drug ,Adult ,medicine.medical_specialty ,Paclitaxel ,Breast Neoplasms ,CAPECITABINE ,Capecitabine ,03 medical and health sciences ,LOCALLY RECURRENT ,Breast cancer ,SDG 3 - Good Health and Well-being ,Internal medicine ,medicine ,Humans ,Aged ,Neoplasm Staging ,Chemotherapy ,business.industry ,Cancer ,medicine.disease ,EFFICACY ,Clinical trial ,BEVACIZUMAB PLUS PACLITAXEL ,030104 developmental biology ,Duration ,business - Abstract
PurposeWe determined if intermittent first-line treatment with paclitaxel plus bevacizumab was not inferior to continuous treatment in patients with HER2-negative, advanced breast cancer.MethodsPatients were randomized to 2x4 cycles or continuous 8 cycles of paclitaxel plus bevacizumab, followed by bevacizumab maintenance treatment until disease progression or unacceptable toxicity. The primary endpoint was overall progression-free survival (PFS). A proportional-hazards regression model was used to estimate the HR. The upper limit of the two-sided 95% CI for the HR was compared with the non-inferiority margin of 1.34.ResultsA total of 420 patients were included with well-balanced characteristics. In the intention-to-treat analysis, median overall PFS was 7.4months (95% CI 6.4-10.0) for intermittent and 9.7 months (95% CI 8.9-10.3) for continuous treatment, with a stratified HR of 1.17 (95% CI 0.88-1.57). Median OS was 17.5 months (95% CI 15.4-21.7) versus 20.9 months (95% CI 17.8-24.0) for intermittent versus continuous treatment, with a HR of 1.38 (95% CI 1.00-1.91). Safety results and actually delivered treatments revealed longer durations of treatment in the continuous arm, without significant unexpected findings.ConclusionIntermittent first-line treatment cannot be recommended in patients with HER2-negative advanced breast cancer. Clinical trial registration: EudraCT 2010-021519-18; BOOG 2010-02.
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- 2018
22. Personalized management of elderly patients with rectal cancer
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Multidisciplinary ,Frailty ,LAPAROSCOPIC-ASSISTED RESECTION ,TOTAL MESORECTAL EXCISION ,Functional recovery ,PHASE-III TRIAL ,Recommendations ,AVOIDING RADICAL SURGERY ,Elderly patients ,RANDOMIZED CLINICAL-TRIAL ,COLORECTAL LIVER METASTASES ,6-MINUTE WALK TEST ,QUALITY-OF-LIFE ,X-RAY BRACHYTHERAPY ,ADVERSE POSTOPERATIVE OUTCOMES ,Rectal cancer - Abstract
With an expanding elderly population and median rectal cancer detection age of 70 years, the prevalence of rectal cancer in elderly patients is increasing. Management is based on evidence from younger patients, resulting in substandard treatments and poor outcomes. Modern management of rectal cancer in the elderly demands patient-centered treatment, assessing frailty rather than chronological age. The heterogeneity of this group, combined with the limited available data, impedes drafting evidence based guidelines. Therefore, a multidisciplinary task force convened experts from the European Society of Surgical Oncology, European Society of Coloproctology, International Society of Geriatric Oncology and the American College Surgeons Commission on Cancer, with the goal of identifying the best practice to promote personalized rectal cancer care in older patients.A crucial element for personalized care was recognized as the routine screening for frailty and geriatrician involvement and personalized care for frail patients. Careful patient selection and improved surgical and perioperative techniques are responsible for a substantial improvement in rectal cancer outcomes. Therefore, properly selected patients should be considered for surgical resection. Local excision can be utilized when balancing oncologic outcomes, frailty and life expectancy. Watch and wait protocols, in expert hands, are valuable for selected patients and adjuncts can be added to improve complete response rates. Functional recovery and patient-reported outcomes are as important as oncologic-specific outcomes in this age group. The above recommendations and others were made based on the best-available evidence to guide the personalized treatment of elderly patients with rectal cancer. (C) 2018 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.
- Published
- 2018
23. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group
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Benjamin Lacas, Alexandra Carmel, Cécile Landais, Stuart J. Wong, Lisa Licitra, Jeffrey S. Tobias, Barbara Burtness, Maria Grazia Ghi, Ezra E.W. Cohen, Cai Grau, Gregory Wolf, Ricardo Hitt, Renzo Corvò, Volker Budach, Shaleen Kumar, Sarbani Ghosh Laskar, Jean-Jacques Mazeron, Lai-Ping Zhong, Werner Dobrowsky, Pirus Ghadjar, Carlo Fallai, Branko Zakotnik, Atul Sharma, René-Jean Bensadoun, Maria Grazia Ruo Redda, Séverine Racadot, George Fountzilas, David Brizel, Paolo Rovea, Athanassios Argiris, Zoltán Takácsi Nagy, Ju-Whei Lee, Catherine Fortpied, Jonathan Harris, Jean Bourhis, Anne Aupérin, Pierre Blanchard, Jean-Pierre Pignon, D.J. Adelstein, M. Alfonsi, Y. Belkacemi, V. Bar-Ad, J. Bernier, Å. Bratland, G. Calais, B. Campbell, J. Caudell, S. Chabaud, E. Chamorey, D. Chaukar, K.N. Choi, O. Choussy, L. Collette, J.J. Cruz, C. Dani, E. Dauzier, A.A. Forastiere, P. Garaud, V. Gregoire, A. Hackshaw, E. Haddad, B.G. Haffty, A. Hansen, S. Hayoz, J.C. Horiot, B. Jeremic, T.G. Karrison, J.A. Langendijk, M. Lapeyre, E. Lartigau, T. Leong, Q.T. Le, P.P.Y. Lee, F. Lewin, A. Lin, A. Lopes, S. Mehta, J. Moon, E. Moyal, B.V. Occéan, P. Olmi, R. Orecchia, B. O'Sullivan, J. Overgaard, C. Petit, H. Quon, G. Sanguineti, T. Satar, J. Simes, C. Simon, C. Sire, S. Staar, C. Stromberger, P. Strojan, S. Temam, D. Thomson, A. Timochenko, V. Torri, V. Tseroni, J. Vermorken, E.E. Vokes, J. Waldron, K.D. Wernecke, J. Widder, B. Zackrisson, Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Damage and Repair in Cancer Development and Cancer Treatment (DARE)
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Oncology ,medicine.medical_treatment ,Review ,030218 nuclear medicine & medical imaging ,law.invention ,0302 clinical medicine ,Randomized controlled trial ,Carcinoma, Squamous Cell/drug therapy ,law ,Antineoplastic Combined Chemotherapy Protocols ,Stage (cooking) ,Adjuvant ,Cancer ,Randomized Controlled Trials as Topic ,PHASE-III TRIAL ,Induction Chemotherapy ,Hematology ,Head and Neck Cancer ,6.5 Radiotherapy and other non-invasive therapies ,Other Physical Sciences ,Head and Neck Neoplasms/therapy ,Chemotherapy, Adjuvant ,Head and Neck Neoplasms ,Randomised Clinical Trials ,030220 oncology & carcinogenesis ,Carcinoma, Squamous Cell ,SQUAMOUS-CELL CARCINOMA ,LOCALLY ADVANCED HEAD ,Chemotherapy ,Individual Patient Data ,Meta-analysis ,Radiotherapy ,medicine.medical_specialty ,Clinical Trials and Supportive Activities ,Oncology and Carcinogenesis ,MITOMYCIN-C ,ADVANCED RESECTABLE HEAD ,Article ,03 medical and health sciences ,Rare Diseases ,Clinical Research ,RADIATION-THERAPY ,Internal medicine ,CONCURRENT CHEMORADIOTHERAPY ,medicine ,Carcinoma ,Humans ,Radiology, Nuclear Medicine and imaging ,Oncology & Carcinogenesis ,Performance status ,business.industry ,Head and neck cancer ,Evaluation of treatments and therapeutic interventions ,Induction chemotherapy ,medicine.disease ,MACH-NC Collaborative Group ,Radiation therapy ,Squamous Cell ,LOCOREGIONALLY ADVANCED-CARCINOMA ,Concomitant ,INDIVIDUAL PARTICIPANT DATA ,business - Abstract
Background and purposeThe Meta-Analysis of Chemotherapy in squamous cell Head and Neck Cancer (MACH-NC) demonstrated that concomitant chemotherapy (CT) improved overall survival (OS) in patients without distant metastasis. We report the updated results.Materials and methodsPublished or unpublished randomized trials including patients with non-metastatic carcinoma randomized between 1965 and 2016 and comparing curative loco-regional treatment (LRT) to LRT+CT or adding another timing of CT to LRT+CT (main question), or comparing induction CT+radiotherapy to radiotherapy+concomitant (or alternating) CT (secondary question) were eligible. Individual patient data were collected and combined using a fixed-effect model. OS was the main endpoint.ResultsFor the main question, 101 trials (18951 patients, median follow-up of 6.5years) were analyzed. For both questions, there were 16 new (2767 patients) and 11 updated trials. Around 90% of the patients had stage III or IV disease. Interaction between treatment effect on OS and the timing of CT was significant (p 
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- 2021
24. The role of chemotherapy in treatment of advanced breast cancer
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MAINTENANCE CHEMOTHERAPY ,GEMCITABINE PLUS PACLITAXEL ,COMBINATION CHEMOTHERAPY ,PHASE-III TRIAL ,RANDOMIZED-TRIAL ,1ST-LINE TREATMENT ,DOUBLE-BLIND ,Duration ,Real-world ,SINGLE-AGENT CHEMOTHERAPY ,QUALITY-OF-LIFE ,Sequence ,CONVENTIONAL DOXORUBICIN ,Chemotherapy ,Advanced breast cancer - Abstract
This review aims to evaluate the role of chemotherapy-containing regimens in the treatment of advanced breast cancer (ABC), with the purpose to optimize selection, sequencing and duration of treatment with the currently available agents for clinical practice. Data from observational as well as randomized phase II and III studies were included. Chemotherapy yielded a median overall survival (OS) of 2 years in registration studies, with comparable efficacy of different agents. Combining chemotherapy agents did not yield OS improvement and caused greater toxicity compared with single-agent chemotherapy. Continuing chemotherapy fill progression or unacceptable toxicity generated greater efficacy without detrimental impact on quality of life compared with a limited amount of cycles. In real-world studies, benefits after third-line chemotherapy were modest compared with first- and second-line. Furthermore, effects of previous chemotherapy predicted effects of next-line therapy in real-world. Physicians increasingly prescribed capecitabine or taxanes as first- or second-line chemotherapy over time.
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- 2020
25. Risk factors for neurocognitive decline in lung cancer patients treated with prophylactic cranial irradiation
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COGNITIVE DYSFUNCTION ,PHASE-III TRIAL ,RANDOMIZED CONTROLLED-TRIAL ,ONCOLOGY ,RTOG 0212 ,METASTASES ,QUALITY-OF-LIFE ,RADIATION-THERAPY ,Cognition impairment ,Risk factor ,Lung cancer ,Prophylactic cranial irradiation ,Neurocognitive decline ,WHOLE-BRAIN RADIOTHERAPY ,EORTC 22003-08004 - Abstract
Background: Prophylactic cranial irradiation (PCI) reduces brain metastasis incidence in lung cancer, however with risk of neurocognitive decline. Nevertheless, risk factors for neurocognitive decline after PCI remain unclear.Methods: We systematically reviewed the PubMed database according to the PRISMA guideline. Inclusion criteria were: randomized clinical trials (RCTs) and observational/single arm trials evaluating PCI, including >= 20 patients, reporting neurocognitive test results for lung cancer. Primary aim: evaluate risk factors associated with neurocognitive decline after PCI.Results: Twenty records were eligible (8 different RCTs, 8 observational studies), including 3553 patients in total (858 NSCLC, 2695 SCLC) of which 73.6% received PCI. Incidence of mild/moderate cognitive decline after PCI varied from 8 to 89% (grading not always provided); for those without PCI, this was 3.4-42%. Interestingly, 23-95% had baseline cognitive impairment. Risk factors were often not reported. In one trial, both age (> 60 years) and higher PCI dose (36 Gy) including twice-daily PCI were associated with a higher risk of cognitive decline. In one trial, white matter abnormalities were more frequent in the concurrent or sandwiched PCI arm, but without significant neuropsychological differences. One trial identified hippocampal sparing PCI to limit the neurocognitive toxicities of PCI and another reported an association between hippocampal dose volume effects and memory decline. As neurocognition was a secondary endpoint in most RCTs, and was assessed by various instruments with often poor/moderate compliance, high-quality data is lacking.Conclusions: Age, PCI dose, regimen and timing might be associated with cognitive impairment after PCI in lung cancer patients, but high-quality data is lacking. Future PCI trials should collect and evaluate possible risk factors systematically.
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- 2020
26. Rectal cancer patients with downstaging after neoadjuvant chemoradiotherapy and radical resection do not benefit from adjuvant chemotherapy
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Kuo Zheng, Ge Sun, Hang Zhang, Xian Hua Gao, Zheng Lou, Wei Zhang, Rong Gui Meng, Lian Jie Liu, Ya Huang, and Li Qiang Hao
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Oncology ,medicine.medical_specialty ,Colorectal cancer ,Adjuvant chemotherapy ,medicine.medical_treatment ,THERAPY ,COLORECTAL-CANCER ,03 medical and health sciences ,0302 clinical medicine ,FOLFOX ,STAGE ,neoadjuvant chemoradiotherapy (NCRT) ,Internal medicine ,COLON ,medicine ,PATHOLOGICAL COMPLETE RESPONSE ,Risk factor ,Rectal cancer ,Letter to the Editor ,Chemotherapy ,Proportional hazards model ,business.industry ,TOTAL MESORECTAL EXCISION ,Consolidation Chemotherapy ,PHASE-III TRIAL ,General Medicine ,downstaging ,medicine.disease ,FLUOROURACIL ,adjuvant chemotherapy ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Original Article ,prognosis ,business ,FOLLOW-UP ,PREOPERATIVE CHEMORADIOTHERAPY ,Neoadjuvant chemoradiotherapy ,medicine.drug - Abstract
Background: Whether adjuvant chemotherapy is beneficial for rectal cancer patients who respond well to neoadjuvant chemoradiotherapy (NCRT) and undergo radical resection is controversial. This study aimed to assess the effect of adjuvant chemotherapy on the oncological outcomes of ypT0-2N0 rectal cancer patients after NCRT and radical resection, and identify the prognostic factors.Methods: The clinical and pathological data of rectal cancer patients with ypT0-2N0 who underwent NCRT and radical resection between January, 2010 and June, 2018 were collected and retrospectively analyzed. The oncological outcomes of the chemotherapy (chemo) group and the non-chemotherapy (non-chemo) group were compared. Multivariate analysis, using a Cox proportional hazard model, was performed to identify independent predictors of oncological outcome.Results: Of the 121 rectal cancer patients enrolled, 90 patients received postoperative adjuvant chemotherapy with no fewer than 3 cycles (the chemo group), and the other 31 patients with fewer than 3 cycles (the non-chemo group). There was no significant difference in the 5-year disease-free survival (DFS) or overall survival (OS) rates between the two groups (DFS: 79.1% vs. 82.9%, P=0.442; OS: 87.5% vs. 78.2%, P=0.667). cT4 is an independent risk factor for OS (HR =4.227, 95% CI: 1.128-15.838, P=0.02) and DFS (HR =4.878, 95% CI: 1.752-13.578). Preoperative consolidation chemotherapy with Capeox or FOLFOX after NCRT significantly improved the DFS rate (HR =0.212, 95% CI: 0.058-0.776, P=0.019).Conclusions: Rectal cancer patients with ypT0-2N0 who underwent NCRT and radical resection did not benefit significantly from postoperative adjuvant chemotherapy. For these patients, cT4 was an independent risk factor for OS and DFS. Preoperative consolidation chemotherapy with Capeox or FOLFOX after NCRT can significantly improve DFS.
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- 2020
27. The role of chemotherapy in treatment of advanced breast cancer: an overview for clinical practice
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Sandra M. E. Geurts, Vivianne C. G. Tjan-Heijnen, Monique E. M. M. Bos, Anouk K. M. Claessens, Khava I.E. Ibragimova, Frans L. G. Erdkamp, and Medical Oncology
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,MAINTENANCE CHEMOTHERAPY ,COMBINATION CHEMOTHERAPY ,Antineoplastic Agents ,Breast Neoplasms ,law.invention ,Capecitabine ,03 medical and health sciences ,DOUBLE-BLIND ,0302 clinical medicine ,Randomized controlled trial ,Quality of life ,SDG 3 - Good Health and Well-being ,law ,QUALITY-OF-LIFE ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Sequence ,CONVENTIONAL DOXORUBICIN ,Medicine ,Humans ,Chemotherapy ,business.industry ,GEMCITABINE PLUS PACLITAXEL ,Cancer ,Combination chemotherapy ,PHASE-III TRIAL ,Hematology ,medicine.disease ,RANDOMIZED-TRIAL ,1ST-LINE TREATMENT ,030104 developmental biology ,Duration ,Real-world ,SINGLE-AGENT CHEMOTHERAPY ,030220 oncology & carcinogenesis ,Toxicity ,Quality of Life ,Observational study ,Taxoids ,Advanced breast cancer ,business ,medicine.drug - Abstract
This review aims to evaluate the role of chemotherapy-containing regimens in the treatment of advanced breast cancer (ABC), with the purpose to optimize selection, sequencing and duration of treatment with the currently available agents for clinical practice. Data from observational as well as randomized phase II and III studies were included. Chemotherapy yielded a median overall survival (OS) of 2 years in registration studies, with comparable efficacy of different agents. Combining chemotherapy agents did not yield OS improvement and caused greater toxicity compared with single-agent chemotherapy. Continuing chemotherapy till progression or unacceptable toxicity generated greater efficacy without detrimental impact on quality of life compared with a limited amount of cycles. In real-world studies, benefits after third-line chemotherapy were modest compared with first- and second-line. Furthermore, effects of previous chemotherapy predicted effects of next-line therapy in real-world. Physicians increasingly prescribed capecitabine or taxanes as first- or second-line chemotherapy over time.
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- 2020
28. Clinical benefit of controversial first line systemic therapies for advanced stage ovarian cancer - ESMO-MCBS scores
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ESMO-MCBS ,PHASE-III TRIAL ,GYNECOLOGIC-ONCOLOGY-GROUP ,Clinical benefit ,RANDOMIZED-TRIAL ,Targeted therapy ,PRIMARY PERITONEAL CANCER ,1ST-LINE TREATMENT ,Ovarian cancer ,CARBOPLATIN PLUS PACLITAXEL ,SINGLE-AGENT CARBOPLATIN ,Chemotherapy ,ADVANCED EPITHELIAL OVARIAN ,INTRAVENOUS CISPLATIN PLUS ,TERM-FOLLOW-UP - Abstract
Background . The magnitude of clinical benefit scale (MCBS) was introduced by the European Society of Medical Oncology (ESMO) to quantify the clinical benefit of therapeutic regimens and to prioritise therapies. It distinguishes curative from palliative treatments and ranks their benefit based on overall survival (OS), progression free survival (PFS), quality of life (QoL) and toxicity. Objective of this study on the first line treatment of ovarian cancer was to evaluate the evidence for the current standard of care using the ESMO-MCBSv1.1 with an emphasis on controversial therapeutic options: intraperitoneal chemotherapy, dose-dense paclitaxel and bevacizumab.Methods: Phase III trials, published since 1992, investigating first line systemic treatment of Federation Internationale de Gynecologie et d'Obstetrique (FIGO) stage IIB-IV epithelial ovarian cancer were included. Since most studies included patients with FIGO stage IV disease or incomplete debulking, all treatments were judged to be palliative. Treatments were graded 5 to 1 on the ESMO-MCBSv1.1, where grades 5 and 4 represent a high level of clinical benefit.Results: 55 studies met the inclusion criteria. ESMO-MCBS scores were calculated for eleven studies that showed a statistically significant benefit of the experimental treatment. Intraperitoneal (ip) cisplatin scored a 4 and 3, but two other studies were negative and therefore not scored on the ESMO-MCBS. Dose-dense paclitaxel showed substantial clinical benefit in one study (score 4), but three studies were negative. Addition of bevacizumab also scored a 4 in one study subgroup including high-risk patients but a 2 in another trial with a larger study population.Conclusion: Based on ESMO-MCBS scores, dose-dense paclitaxel and intraperitoneal chemotherapy cannot be recommended as standard treatment. Bevacizumab should be considered only in the high-risk population. The ESMO-MCBSv1.1. helps to summarise reported studies on controversial treatment regimens, and identifies their weaknesses.
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- 2018
29. Intermediate Dose Low-Molecular-Weight Heparin for Thrombosis Prophylaxis: Systematic Review with Meta-Analysis and Trial Sequential Analysis
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Iwan C. C. van der Horst, Reinold O. B. Gans, Frederik Keus, Karina Meijer, Wouter Bult, Ruben J. Eck, Jørn Wetterslev, Lifelong Learning, Education & Assessment Research Network (LEARN), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Cardiovascular Centre (CVC), and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
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medicine.medical_specialty ,DALTEPARIN THROMBOPROPHYLAXIS ,medicine.drug_class ,CELL LUNG-CANCER ,Placebo-controlled study ,Low molecular weight heparin ,030204 cardiovascular system & hematology ,PLACEBO-CONTROLLED TRIAL ,law.invention ,03 medical and health sciences ,DOUBLE-BLIND ,0302 clinical medicine ,Randomized controlled trial ,systematic review ,law ,Internal medicine ,Medicine ,Humans ,DEEP-VEIN THROMBOSIS ,low-molecular-weight heparin ,thrombosis ,VENOUS THROMBOEMBOLISM ,business.industry ,TOTAL HIP-REPLACEMENT ,PHASE-III TRIAL ,Hematology ,Number needed to harm ,Odds ratio ,Heparin, Low-Molecular-Weight ,RANDOMIZED CONTROLLED-TRIAL ,LMWH ,meta-analysis ,Relative risk ,Meta-analysis ,Number needed to treat ,COMPRESSION STOCKINGS ,Cardiology and Cardiovascular Medicine ,business ,030215 immunology - Abstract
Different doses of low-molecular-weight heparin (LMWH) are registered and used for thrombosis prophylaxis. We assessed benefits and harms of thrombosis prophylaxis with a predefined intermediate-dose LMWH compared with placebo or no treatment in patients at risk of venous thromboembolism (VTE). We performed a systematic review with meta-analyses and trial sequential analyses (TSA) following The Cochrane Handbook for Systematic Reviews of Interventions. Medline, Cochrane CENTRAL, Web of Science, and Embase were searched up to December 2018. Trials were evaluated for risk of bias and quality of evidence was assessed following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Seventy randomized trials with 34,046 patients were included. Eighteen (26%) had overall low risk of bias. There was a small statistically significant effect of LMWH on all-cause mortality (risk ratio [RR]: 0.96; TSA-adjusted confidence interval [TSA-adjusted CI]: 0.94–0.98) which disappeared in sensitivity analyses excluding ambulatory cancer patients (RR: 0.99; TSA-adjusted CI: 0.84–1.16). There was moderate-quality evidence for a statistically significant beneficial effect on symptomatic VTE (odds ratio [OR]: 0.59; TSA-adjusted CI: 0.53–0.67; number needed to treat [NNT]: 76; 95% CI: 60–106) and a statistically significant harmful effect on major bleeding (Peto OR: 1.66; TSA-adjusted CI: 1.31–2.10; number needed to harm [NNH]: 212; 95% CI: 142–393). There were no significant intervention effects on serious adverse events. The use of intermediate-dose LMWH for thrombosis prophylaxis compared with placebo or no treatment was associated with a small statistically significant reduction of all-cause mortality that disappeared in sensitivity analyses excluding trials that evaluated LMWH for anticancer treatment. Intermediate-dose LMWH provides benefits in terms of VTE prevention while it increases major bleeding.
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- 2019
30. Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC
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Socinski, M. A., Jotte, R. M., Cappuzzo, F., Orlandi, F., Stroyakovskiy, D., Nogami, N., Rodriguez-Abreu, D., Moro-Sibilot, D., Thomas, C. A., Barlesi, F., Finley, G., Kelsch, C., Lee, A., Coleman, S., Deng, Y., Shen, Y., Kowanetz, M., Lopez-Chave, A., Sandler, A., Reck, M., Soto Parra, H, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Pulmonologie, and MUMC+: MA Med Staf Spec Longziekten (9)
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0301 basic medicine ,Oncology ,Male ,Vascular Endothelial Growth Factor A ,Lung Neoplasms ,MULTICENTER ,THERAPY ,B7-H1 Antigen ,Carboplatin ,chemistry.chemical_compound ,0302 clinical medicine ,Monoclonal ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Anaplastic Lymphoma Kinase ,Neoplasm Metastasis ,Non-Small-Cell Lung ,DOCETAXEL ,education.field_of_study ,Aged ,Antibodies, Monoclonal ,Bevacizumab ,Carcinoma, Non-Small-Cell Lung ,Female ,Genes, erbB-1 ,Humans ,Middle Aged ,Mutation ,Paclitaxel ,Receptor Protein-Tyrosine Kinases ,Survival Analysis ,Immunotherapy ,Hazard ratio ,PHASE-III TRIAL ,General Medicine ,CHEMOTHERAPY ,OPEN-LABEL ,CANCER ,Docetaxel ,030220 oncology & carcinogenesis ,medicine.drug ,medicine.medical_specialty ,Population ,BEVACIZUMAB ,Antibodies ,03 medical and health sciences ,Atezolizumab ,Internal medicine ,Lung cancer ,education ,Survival analysis ,erbB-1 ,business.industry ,Carcinoma ,medicine.disease ,030104 developmental biology ,chemistry ,Genes ,ANTIBODY ,CELLS ,business - Abstract
Background The cancer-cell–killing property of atezolizumab may be enhanced by the blockade of vascular endothelial growth factor–mediated immunosuppression with bevacizumab. This open-label, phase 3 study evaluated atezolizumab plus bevacizumab plus chemotherapy in patients with metastatic nonsquamous non–small-cell lung cancer (NSCLC) who had not previously received chemotherapy. Methods We randomly assigned patients to receive atezolizumab plus carboplatin plus paclitaxel (ACP), bevacizumab plus carboplatin plus paclitaxel (BCP), or atezolizumab plus BCP (ABCP) every 3 weeks for four or six cycles, followed by maintenance therapy with atezolizumab, bevacizumab, or both. The two primary end points were investigator-assessed progression-free survival both among patients in the intention-to-treat population who had a wild-type genotype (WT population; patients with EGFR or ALK genetic alterations were excluded) and among patients in the WT population who had high expression of an effector T-cell (Teff) gene signature in the tumor (Teff-high WT population) and overall survival in the WT population. The ABCP group was compared with the BCP group before the ACP group was compared with the BCP group. Results In the WT population, 356 patients were assigned to the ABCP group, and 336 to the BCP group. The median progression-free survival was longer in the ABCP group than in the BCP group (8.3 months vs. 6.8 months; hazard ratio for disease progression or death, 0.62; 95% confidence interval [CI], 0.52 to 0.74; P
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- 2018
31. Effect of Neoadjuvant Chemoradiotherapy on Health-Related Quality of Life in Esophageal or Junctional Cancer
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J. Jan B. van Lanschot, Jannet C. Beukema, Herman van Dekken, Janny G. Reinders, Olivier R. Busch, Fiebo J.W. ten Kate, Bo Jan Noordman, Mathilde G. E. Verdam, Johannes J. Bonenkamp, Grard A. P. Nieuwenhuijzen, Hugo W. Tilanus, Geert-Jan Creemers, Pieter van Hagen, Mark I. van Berge Henegouwen, Tom Rozema, Mirjam A. G. Sprangers, Cornelis J. A. Punt, John T. M. Plukker, Geke A. P. Hospers, Ate van der Gaast, Reinoud J. B. Blaisse, Maarten C.C.M. Hulshof, Bas P. L. Wijnhoven, Katharina Biermann, Anna H.M. Piet, Henk M.W. Verheul, Hanneke W. M. van Laarhoven, Ernst Jan Spillenaar Bilgen, Ewout W. Steyerberg, Miguel A. Cuesta, Maurice J.C. van der Sangen, Sjoerd M. Lagarde, Caroline M. van Rij, Surgery, Pathology, Radiotherapy, Public Health, Medical Oncology, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), APH - Mental Health, CCA - Cancer Treatment and Quality of Life, APH - Personalized Medicine, Medical Psychology, Graduate School, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Oncology, APH - Aging & Later Life, APH - Methodology, CCA - Cancer Treatment and quality of life, Medical oncology, Radiation Oncology, Clinical pharmacology and pharmacy, and Amsterdam Gastroenterology Endocrinology Metabolism
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Cancer Research ,medicine.medical_specialty ,CARCINOMA ,SURGERY ,medicine.medical_treatment ,030230 surgery ,Gastroenterology ,THERAPY ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14] ,Cancer development and immune defence Radboud Institute for Health Sciences [Radboudumc 2] ,CHEMORADIATION ,0302 clinical medicine ,All institutes and research themes of the Radboud University Medical Center ,Quality of life ,Randomized controlled trial ,SDG 3 - Good Health and Well-being ,law ,Internal medicine ,Medicine ,EXTENDED TRANSTHORACIC RESECTION ,business.industry ,PERIOPERATIVE CHEMOTHERAPY ,LONG-TERM SURVIVORS ,Cancer ,PHASE-III TRIAL ,ADENOCARCINOMA ,Esophageal cancer ,medicine.disease ,Carboplatin ,humanities ,Surgery ,Radiation therapy ,Oncology ,chemistry ,Esophagectomy ,030220 oncology & carcinogenesis ,business ,Chemoradiotherapy ,CLINICAL-TRIALS - Abstract
Purpose To compare pre-agreed health-related quality of life (HRQOL) domains in patients with esophageal or junctional cancer who received neoadjuvant chemoradiotherapy (nCRT) followed by surgery or surgery alone. Secondary aims were to examine the effect of nCRT on HRQOL before surgery and the effect of surgery on HRQOL. Patients and Methods Patients were randomly assigned to nCRT (carboplatin plus paclitaxel with concurrent 41.4-Gy radiotherapy) followed by surgery or surgery alone. HRQOL was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 (QLQ-C30) and –Oesophageal Cancer Module (QLQ-OES24) questionnaires pretreatment and at 3, 6, 9, and 12 months postoperatively. The nCRT group also received preoperative questionnaires. Physical functioning (PF; QLQ-C30) and eating problems (EA; QLQ-OES24) were chosen as predefined primary end points. Predefined secondary end points were global QOL (GQOL; QLQ-C30), fatigue (FA; QLQ-C30), and emotional problems (EM; QLQ-OES24). Results A total of 363 patients were analyzed. No statistically significant differences in postoperative HRQOL were found between treatment groups. In the nCRT group, PF, EA, GQOL, FA, and EM scores deteriorated 1 week after nCRT (Cohen’s d: −0.93, P < .001; 0.47, P < .001; −0.84, P < .001; 1.45, P < .001; and 0.32, P = .001, respectively). In both treatment groups, all end points declined 3 months postoperatively compared with baseline (Cohen’s d: −1.00, 0.33, −0.47, −0.34, and 0.33, respectively; all P < .001), followed by a continuous gradual improvement. EA, GQOL, and EM were restored to baseline levels during follow-up, whereas PF and FA remained impaired 1 year postoperatively (Cohen’s d: 0.52 and −0.53, respectively; both P < .001). Conclusion Although HRQOL declined during nCRT, no effect of nCRT was apparent on postoperative HRQOL compared with surgery alone. In addition to the improvement in survival, these findings support the view that nCRT according to the Chemoradiotherapy for Esophageal Cancer Followed by Surgery Study–regimen can be regarded as a standard of care.
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- 2018
32. Predictive biomarkers for response to EGFR-directed monoclonal antibodies for advanced squamous cell lung cancer
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David R. Spigel, Nick Thatcher, Edward S. Kim, Philip Bonomi, Melissa Culligan, Silvia Novello, C. Bellomo, Maurice Pérol, Paul A. Bunn, Martin Reck, Mark A. Socinski, Coleman K. Obasaju, Fred R. Hirsch, Johan Vansteenkiste, James R. Jett, Keith M. Kerr, Corey J. Langer, Heather A. Wakelee, Luis Paz-Ares, David R. Gandara, Craig H. Reynolds, Jeffrey D. Bradley, Suresh S. Ramalingam, Egbert F. Smit, Ronald B. Natale, and Fundación Lilly
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Lung Neoplasms ,medicine.medical_treatment ,Gene Dosage ,Angiogenesis Inhibitors ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Antineoplastic Combined Chemotherapy Protocols ,030212 general & internal medicine ,Lung ,Randomized Controlled Trials as Topic ,Cetuximab ,EGFR-directed monoclonal antibodies ,PHASE-III TRIAL ,Hematology ,CHEMOTHERAPY ,OPEN-LABEL ,Chemotherapy regimen ,CETUXIMAB ,ErbB Receptors ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Monoclonal ,Biomarker (medicine) ,CLINICAL-PRACTICE GUIDELINES ,Life Sciences & Biomedicine ,medicine.drug ,Reviews ,STAGE IV ,Antibodies, Monoclonal, Humanized ,CISPLATIN PLUS GEMCITABINE ,Gene dosage ,non-small-cell lung cancer, squamous cell lung cancer, EGFR-directed monoclonal antibodies ,03 medical and health sciences ,squamous cell lung cancer ,Biomarkers, Tumor ,medicine ,Humans ,Lung cancer ,Science & Technology ,business.industry ,Immunotherapy ,medicine.disease ,non-small-cell lung cancer ,Drug Resistance, Neoplasm ,Mutation ,Cancer research ,1ST-LINE THERAPY ,business ,GROWTH-FACTOR RECEPTOR ,FOLLOW-UP ,Necitumumab - Abstract
The concept of predictive biomarkers for EGFR-directed mAbs addressed in this article were originally discussed at a meeting convened by Eli Lilly and Company that covered topics for physician education on SqCLC, for which participants, includ- ing some of the authors on this publication, received an honor- arium. This publication was developed separately from the meeting, and the authors received no payment in relation to the development of this publication. The authors would like to thank Charlene Rivera, PhD and Rob Kite, BSc (Hons), at Complete HealthVizion for assistance with writing and revising the draft manuscript on the basis of detailed feedback from all authors. Primary responsibility for the opinions, conclusions, and interpretation of data lay with the authors, and all authors approved the final version of the manuscript. Background: Upregulated expression and aberrant activation of the epidermal growth-factor receptor (EGFR) are found in lung cancer, making EGFR a relevant target for non-small-cell lung cancer (NSCLC). Treatment with anti-EGFR monoclonal antibodies (mAbs) is associated with modest improvement in overall survival in patients with squamous cell lung cancer (SqCLC) who have a significant unmet need for effective treatment options. While there is evidence that using EGFR gene copy number, EGFR mutation, and EGFR protein expression as biomarkers can help select patients who respond to treatment, it is important to consider biomarkers for response in patients treated with combination therapies that include EGFR mAbs. Design: Randomized trials of EGFR-directed mAbs cetuximab and necitumumab in combination with chemotherapy, immunotherapy, or antiangiogenic therapy in patients with advanced NSCLC, including SqCLC, were searched in the literature. Results of associations of potential biomarkers and outcomes were summarized. Results: Data from phase III clinical trials indicate that patients with NSCLC, including SqCLC, whose tumors express high levels of EGFR protein (H-score of ≥200) and/or gene copy numbers of EGFR (e.g. ≥40% cells with ≥4 EGFR copies as detected by fluorescence in situ hybridization; gene amplification in ≥10% of analyzed cells) derive greater therapeutic benefits from EGFR-directed mAbs. Biomarker data are limited for EGFR mAbs used in combination with immunotherapy and are absent when used in combination with antiangiogenic agents. Conclusions: Therapy with EGFR-directed mAbs in combination with chemotherapy is associated with greater clinical benefits in patients with NSCLC, including SqCLC, whose tumors express high levels of EGFR protein and/or have increased EGFR gene copy number. These data support validating the role of these as biomarkers to identify those patients who derive the greatest clinical benefit from EGFR mAb therapy. However, data on biomarkers for EGFR-directed mAbs combined with immunotherapy or antiangiogenic agents remain limited. Sí
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- 2018
33. Controlled-release pregabalin in the treatment of fibromyalgia
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PHARMACOKINETICS ,Fibromyalgia ,DIAGNOSTIC-CRITERIA ,PHASE-III TRIAL ,HEALTH-CARE COSTS ,PLACEBO-CONTROLLED TRIAL ,DULOXETINE ,OF-RHEUMATOLOGY 1990 ,DOUBLE-BLIND ,pharmacological treatment ,pregabalin ,MEDICATION ADHERENCE ,controlled-release pregabalin ,METAANALYSIS - Abstract
Introduction: Fibromyalgia (FM) is a chronic disorder whose symptoms of musculo-skeletal pain, fatigue, sleep disturbances, and cognitive impairment pervade the personal, occupational, and social aspects of a patient's life. Together with the antidepressants duloxetine and milnacipran, the anticonvulsant pregabalin (PGB) is one of the three drugs approved by the Food and Drug Administration for the treatment of FM. The aim of this narrative review is to summarize the data relating to the efficacy and safety of the controlled-release formulation of PGB (PGB-CR) in patients with FM. Areas covered: Efforts by the pharmaceutical industry have led to the introduction of new formulations of already approved drugs to enhance treatment convenience and adherence. Expert opinion: Although there are no published studies specifically comparing PGB-CR and PGB-IR formulations in FM patients, the efficacy and safety profiles of PGB-CR seem to be similar to those of the IR formulation, and the convenience of once-daily dosing potentially enhances patient compliance. However, the amount of evidence is not sufficient to draw any definite conclusions, and further studies of larger patient samples are needed.
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- 2018
34. Personalized management of elderly patients with rectal cancer: Expert recommendations of the European Society of Surgical Oncology, European Society of Coloproctology, International Society of Geriatric Oncology, and American College of Surgeons Commission on Cancer
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Oriana Nanni, Nicola de Liguori Carino, Alois Fürst, Harm J. T. Rutten, Avni M. Desai, David E. Winchester, Nicole M. Saur, Jean Pierre Gerard, Steven D. Wexner, Mattia Altini, Mariana Berho, Albert Wolthuis, Mark Lawler, Valery E.P.P. Lemmens, Arthur Sun Myint, Siri Rostoft, Isacco Montroni, Fabio Potenti, Demetris Papamichael, Marta Penna, Roel Hompes, Stefano Cascinu, Riccardo A. Audisio, Giampaolo Ugolini, Geerard L. Beets, Monica Millan, Antonino Spinelli, Ian R. Daniels, Montroni, I., Ugolini, G., Saur, N. M., Spinelli, A., Rostoft, S., Millan, M., Wolthuis, A., Daniels, I. R., Hompes, R., Penna, M., Furst, A., Papamichael, D., Desai, A. M., Cascinu, S., Gerard, J. -P., Myint, A. S., Lemmens, V. E. P. P., Berho, M., Lawler, M., De Liguori Carino, N., Potenti, F., Nanni, O., Altini, M., Beets, G., Rutten, H., Winchester, D., Wexner, S. D., Audisio, R. A., and Public Health
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medicine.medical_specialty ,Colorectal cancer ,Frail Elderly ,AVOIDING RADICAL SURGERY ,Recommendations ,6-MINUTE WALK TEST ,03 medical and health sciences ,0302 clinical medicine ,Quality of life (healthcare) ,SDG 3 - Good Health and Well-being ,QUALITY-OF-LIFE ,Surgical oncology ,X-RAY BRACHYTHERAPY ,medicine ,Prevalence ,Humans ,Rectal cancer ,Precision Medicine ,Intensive care medicine ,Geriatric Assessment ,Aged ,Multidisciplinary ,Evidence-Based Medicine ,LAPAROSCOPIC-ASSISTED RESECTION ,Frailty ,business.industry ,Rectal Neoplasms ,TOTAL MESORECTAL EXCISION ,Patient Selection ,Cancer ,Functional recovery ,PHASE-III TRIAL ,General Medicine ,Evidence-based medicine ,Perioperative ,Recovery of Function ,Precision medicine ,medicine.disease ,RANDOMIZED CLINICAL-TRIAL ,COLORECTAL LIVER METASTASES ,Elderly patients ,Oncology ,Geriatric oncology ,030220 oncology & carcinogenesis ,ADVERSE POSTOPERATIVE OUTCOMES ,030211 gastroenterology & hepatology ,Surgery ,business - Abstract
With an expanding elderly population and median rectal cancer detection age of 70 years, the prevalence of rectal cancer in elderly patients is increasing. Management is based on evidence from younger patients, resulting in substandard treatments and poor outcomes. Modern management of rectal cancer in the elderly demands patient-centered treatment, assessing frailty rather than chronological age. The heterogeneity of this group, combined with the limited available data, impedes drafting evidence based guidelines. Therefore, a multidisciplinary task force convened experts from the European Society of Surgical Oncology, European Society of Coloproctology, International Society of Geriatric Oncology and the American College Surgeons Commission on Cancer, with the goal of identifying the best practice to promote personalized rectal cancer care in older patients. A crucial element for personalized care was recognized as the routine screening for frailty and geriatrician involvement and personalized care for frail patients. Careful patient selection and improved surgical and perioperative techniques are responsible for a substantial improvement in rectal cancer outcomes. Therefore, properly selected patients should be considered for surgical resection. Local excision can be utilized when balancing oncologic outcomes, frailty and life expectancy. Watch and wait protocols, in expert hands, are valuable for selected patients and adjuncts can be added to improve complete response rates. Functional recovery and patient-reported outcomes are as important as oncologic-specific outcomes in this age group. The above recommendations and others were made based on the best-available evidence to guide the personalized treatment of elderly patients with rectal cancer. (C) 2018 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.
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- 2018
35. The Current Role of Whole Brain Radiation Therapy in Non–Small Cell Lung Cancer Patients
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STEREOTACTIC RADIOSURGERY ,SINGLE METASTASES ,Radiotherapy ,Brain irradiation ,PHASE-III TRIAL ,ALK translocation ,RANDOMIZED CONTROLLED-TRIAL ,OPEN-LABEL ,CLINICAL-TRIAL ,Targeted therapy ,PROPHYLACTIC CRANIAL IRRADIATION ,QUALITY-OF-LIFE ,CEREBRAL METASTASES ,Stereotactic radiotherapy ,EGFR mutation - Abstract
The incidence of brain metastases has increased in patients with NSCLC as a result of better systemic disease control and advances in imaging modalities. Whole brain radiotherapy (WBRT) has been the mainstay treatment of multiple symptomatic brain metastases for years. A number of recent publications have questioned its place in the absence of a survival and quality of life benefit and the possible risk for long-term neurotoxicity. Omission or deferral of WBRT and strategies consisting of stereotactic radiosurgery or delivery of systemic therapies alone are being proposed more and more. However, critical analysis of the literature shows that WBRT still has relevant indications in well-selected patients. Within this review, we discuss the place of WBRT in the modern management of patients with NSCLC. (C) 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
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- 2017
36. Increased life expectancy as a result of non-hormonal targeted therapies for HER2 or hormone receptor positive metastatic breast cancer
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Human epidermal growth factor receptor 2 ,Breast neoplasm ,LAPATINIB PLUS CAPECITABINE ,PHASE-III TRIAL ,Estrogen receptors ,Survival analysis ,Progesterone receptors ,OPEN-LABEL ,RANDOMIZED-TRIAL ,1ST-LINE TREATMENT ,DOUBLE-BLIND ,TRASTUZUMAB EMTANSINE ,Molecular targeted therapy ,GROWTH-FACTOR RECEPTOR ,SURVIVAL ANALYSIS ,2ND-LINE TREATMENT - Abstract
This article aimed to assess the clinical effectiveness of non-hormonal targeted therapies (TTs) in terms of increase of median progression-free survival (PFS) and overall survival (OS) in receptor-positive metastatic breast cancer (MBC) patients by performing a systematic review and meta-analysis. We systematically searched relevant randomized controlled trials and extracted data about number of patients on targeted and comparator therapy, receptor status, line of treatment, median PFS and OS, p values, hazard ratios (HRs) and 95% confidence intervals (CI). Inverse variance was used to estimate pooled HRs, chi-square test for heterogeneity and Jadad scale for quality were applied. Thirty-eight studies (n = 17,192 patients) were eligible for inclusion. TTs added 3.3 months to the median PFS [0.7-9.6; HRs 0.74, 95% CI 0.71-0.77] of receptor-positive MBC patients and prolonged their median OS with 3.5 months [0-4.7; HRs 0.90, 95% CI 0.82-0.98]. The highest increase in median PFS of 3.6 months was found in HER2-/hormone receptor(HR)+ patients, while the highest increase in median OS of 7.2 months was observed in HER2+/HRmixed status patients. First-line ITs were most effective in increasing the median PFS in the HR+/HER2- group with 2.0 months, and in the HER2+/HRmixed group by adding 4.7 months to the median OS. Second-line TTs were most effective for HER2-/HR+ patients by adding 2.6 months to their PFS, and for HER2+/HRmixed patients by adding 3.1 months to their median OS. Albeit small, the gain in months of median PFS and median OS was significant. Importantly, the results reported show large variation, and thus routinely applying a personalized approach seems warranted. (C) 2017 Elsevier Ltd. All rights reserved.
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- 2017
37. Alternating Treatment With Pazopanib and Everolimus vs Continuous Pazopanib to Delay Disease Progression in Patients With Metastatic Clear Cell Renal Cell Cancer The ROPETAR Randomized Clinical Trial
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Martijn P. Lolkema, Marco B. Polee, Olaf Loosveld, Paul Hamberg, Geert A. Cirkel, Stefan Sleijfer, Heinz-Josef Klümpen, Johanna E.A. Portielje, Emile E. Voest, Frank P. J. Peters, Vincent van der Noort, Gerard Groenewegen, Maartje Los, Maureen J.B. Aarts, Franchette W P J van den Berkmortel, Laurens V. Beerepoot, John B. A. G. Haanen, Metin Tascilar, M. Wouter Dercksen, Oncology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Medical Oncology, Interne Geneeskunde, MUMC+: MA Medische Oncologie (9), and RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy
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0301 basic medicine ,Oncology ,Male ,Cancer Research ,Kaplan-Meier Estimate ,GUIDELINES ,THERAPY ,law.invention ,0302 clinical medicine ,Randomized controlled trial ,Renal cell carcinoma ,law ,Antineoplastic Combined Chemotherapy Protocols ,Clinical endpoint ,Aged, 80 and over ,Sulfonamides ,PHASE-III TRIAL ,Middle Aged ,Kidney Neoplasms ,030220 oncology & carcinogenesis ,Disease Progression ,Female ,medicine.drug ,Adult ,medicine.medical_specialty ,Indazoles ,CARCINOMA ,Disease-Free Survival ,Pazopanib ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Internal medicine ,SURVEILLANCE ,medicine ,Carcinoma ,Mucositis ,Humans ,Everolimus ,SUNITINIB RECHALLENGE ,Carcinoma, Renal Cell ,Aged ,DRUG-RESISTANCE ,business.industry ,medicine.disease ,EFFICACY ,Surgery ,Clear cell renal cell carcinoma ,030104 developmental biology ,Pyrimidines ,Quality of Life ,business - Abstract
Importance To our knowledge, this is the first randomized clinical trial evaluating an alternating treatment regimen in an attempt to delay disease progression in clear cell renal cell carcinoma. Objective To test our hypothesis that an 8-week rotating treatment schedule with pazopanib and everolimus delays disease progression, exhibits more favorable toxic effects, and improves quality of life when compared with continuous treatment with pazopanib. Design, Setting, and Participants This was an open-label, randomized (1:1) study (ROPETAR trial). In total, 101 patients with treatment-naive progressive metastatic clear cell renal cell carcinoma were enrolled between September 2012 and April 2014 from 17 large peripheral or academic hospitals in The Netherlands and followed for at least one year. Interventions First-line treatment consisted of either an 8-week alternating treatment schedule of pazopanib 800 mg/d and everolimus 10 mg/d (rotating arm) or continuous pazopanib 800 mg/d (control arm) until progression. After progression, patients made a final rotation to either pazopanib or everolimus monotherapy (rotating arm) or initiated everolimus (control arm). Main Outcome and Measures The primary end point was survival until first progression or death. Secondary end points included time to second progression or death, toxic effects, and quality of life. Results A total of 52 patients were randomized to the rotating arm (median [range] age, 65 [44-87] years) and 49 patients to the control arm (median [range] age, 67 [38-82] years). Memorial Sloan Kettering Cancer Center risk category was favorable in 26% of patients, intermediate in 58%, and poor in 15%. Baseline characteristics and risk categories were well balanced between arms. One-year PFS1 for rotating treatment was 45% (95% CI, 33-60) and 32% (95% CI, 21-49) for pazopanib (control). Median time until first progression or death for rotating treatment was 7.4 months (95% CI, 5.6-18.4) and 9.4 months (95% CI, 6.6-11.9) for pazopanib (control) ( P = .37). Mucositis, anorexia, and dizziness were more prevalent in the rotating arm during first-line treatment. No difference in quality of life was observed. Conclusions and Relevance Rotating treatment did not result in prolonged progression-free-survival, fewer toxic effects, or improved quality of life. First-line treatment with a vascular endothelial growth factor inhibitor remains the optimal approach in metastatic clear cell renal cell carcinoma. Trial Registration clinicaltrials.gov Identifier:NCT01408004
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- 2017
38. Safety and utility of image-guided research biopsies in relapsed high-grade serous ovarian carcinoma—experience of the BriTROC consortium
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Andrew R Clamp, Mercedes Jimenez-Linan, Eleanor C Brockbank, Axel Walther, Marcia Hall, Rosalind Glasspool, Hani Gabra, Darren Ennis, Jon Stobo, Geoff Hall, Susan Freeman, Cheryl Wilson, Richard J. Edmondson, Ana Montes, Christina Fotopoulou, Iain A. McNeish, James Paul, Luisa Moore, Sudha Sundar, Teodora Goranova, Liz-Anne Lewsley, Geoff Macintyre, David Kay, Anna M. Piskorz, Charlie Gourley, Michelle Lockley, James D. Brenton, Macintyre, Geoff [0000-0003-3906-467X], Moore, Luiza [0000-0001-5315-516X], Brenton, James [0000-0002-5738-6683], and Apollo - University of Cambridge Repository
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0301 basic medicine ,Oncology ,Cancer Research ,DNA Mutational Analysis ,CANCER GENOMICS ,tagged-amplicon sequencing ,Phosphatidylinositol 3-Kinases ,0302 clinical medicine ,Ovarian carcinoma ,License ,Peritoneal Neoplasms ,Cervical cancer ,Aged, 80 and over ,Ovarian Neoplasms ,Manchester Cancer Research Centre ,Liver Neoplasms ,WOMEN ,PHASE-III TRIAL ,DNA, Neoplasm ,CHEMOTHERAPY ,Middle Aged ,OPEN-LABEL ,ErbB Receptors ,Serous fluid ,ovarian cancer ,Liver ,030220 oncology & carcinogenesis ,Lymphatic Metastasis ,Female ,Peritoneum ,Life Sciences & Biomedicine ,Omentum ,EPITHELIAL OVARIAN ,Adult ,Image-Guided Biopsy ,Proto-Oncogene Proteins B-raf ,medicine.medical_specialty ,image-guided ,Class I Phosphatidylinositol 3-Kinases ,BEVACIZUMAB ,Pain ,Proto-Oncogene Proteins p21(ras) ,03 medical and health sciences ,Breast cancer ,Internal medicine ,high grade serous carcinoma ,Journal Article ,Carcinoma ,medicine ,BREAST-CANCER ,Humans ,biopsy ,Oncology & Carcinogenesis ,Lung cancer ,methanol fixation ,Aged ,Science & Technology ,MUTATIONS ,business.industry ,ResearchInstitutes_Networks_Beacons/mcrc ,PTEN Phosphohydrolase ,medicine.disease ,030104 developmental biology ,Feasibility Studies ,next-generation sequencing ,Lymph Nodes ,Neoplasm Grading ,Tumor Suppressor Protein p53 ,business ,Translational Therapeutics ,1112 Oncology And Carcinogenesis ,RESISTANCE - Abstract
BACKGROUND: Investigating tumour evolution and acquired chemotherapy resistance requires analysis of sequential tumour material. We describe the feasibility of obtaining research biopsies in women with relapsed ovarian high-grade serous carcinoma (HGSC).METHODS: Women with relapsed ovarian HGSC underwent either image-guided biopsy or intra-operative biopsy during secondary debulking, and samples were fixed in methanol-based fixative. Tagged-amplicon sequencing was performed on biopsy DNA.RESULTS: We screened 519 patients in order to enrol 220. Two hundred and two patients underwent successful biopsy, 118 of which were image-guided. There were 22 study-related adverse events (AE) in the image-guided biopsies, all grades 1 and 2; pain was the commonest AE. There were pre-specified significant AE in 3/118 biopsies (2.5%). 87% biopsies were fit-for-purpose for genomic analyses. Median DNA yield was 2.87 μg, and was higher in biopsies utilising 14 G or 16 G needles compared to 18 G. TP53 mutations were identified in 94.4% patients.CONCLUSIONS: Obtaining tumour biopsies for research in relapsed HGSC is safe and feasible. Adverse events are rare. The large majority of biopsies yield sufficient DNA for genomic analyses-we recommend use of larger gauge needles and methanol fixation for such biopsies, as DNA yields are higher but with no increase in AEs.British Journal of Cancer advance online publication, 30 March 2017; doi:10.1038/bjc.2017.86 www.bjcancer.com.
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- 2017
39. The Potential of Combined Immunotherapy and Antiangiogenesis for the Synergistic Treatment of Advanced NSCLC
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Antiangiogenesis ,CELL LUNG-CANCER ,PHASE-III TRIAL ,BEVACIZUMAB BEV ,RANDOMIZED CONTROLLED-TRIAL ,NSCLC ,VEGF-A ,DOUBLE-BLIND ,PATIENTS PTS ,ENDOTHELIAL GROWTH-FACTOR ,METASTATIC MELANOMA ,Immunotherapy ,Combination therapy ,TUMOR MICROENVIRONMENT - Abstract
Over the past few years, there have been considerable advances in the treatments available to patients with metastatic or locally advanced NSCLC, particularly those who have progressed during first-line treatment. Some of the treatment options available to patients are discussed here, with a focus on checkpoint inhibitor immunotherapies (nivolumab and pembrolizumab) and antiangiogenic agents (bevacizumab, ramucirumab, and nintedanib). It is hypothesized that combining immunotherapy with antiangiogenic treatment may have a synergistic effect and enhance the efficacy of both treatments. In this review, we explore the theory and potential of this novel treatment option for patients with advanced NSCLC. We discuss the growing body of evidence that proangiogenic factors can modulate the immune response (both by reducing T-cell infiltration into the tumor microenvironment and through systemic effects on immune-regulatory cell function), and we examine the preclinical evidence for combining these treatments. Potential challenges are also considered, and we review the preliminary evidence of clinical efficacy and safety with this novel combination in a variety of solid tumor types. (C) 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
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- 2017
40. Adjuvant versus Neoadjuvant Radiochemotherapy for Locally Advanced Rectal Cancer A Progress Report of a Phase-III Randomized Trial (Protocol CAO/ARO/AIO-94).
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Sauer, Rolf, Fietkau, Rainer, Wittekind, Christian, Martus, Peter, Rödel, Claus, Hohenberger, Werner, Jatzko, Gerhard, Sabitzer, Hubert, Karstens, Johann-Hinrich, Becker, Heinz, Hess, Clemens, and Raab, Rudolf
- Abstract
Copyright of Strahlentherapie und Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2001
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41. RasGRP1 is a potential biomarker for stratifying anti-EGFR therapy response in colorectal cancer
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David Barras, Mauro Delorenzi, Delphine Grun, Michelle R. Mahoney, Yi Miao, Robert S. Warren, Andrew B. Nixon, S. Tejpar, Chih Yang Wang, Mary Matli, Oghenekevwe M. Gbenedio, Caroline Bonnans, Philippe Depeille, Ace J. Hatch, K. Christopher Garcia, Jeroen P. Roose, and Alan P. Venook
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0301 basic medicine ,Oncology ,Colorectal cancer ,receptor ,Cetuximab ,Datasets as Topic ,Kaplan-Meier Estimate ,Signal transduction ,multiple intestinal neoplasia ,medicine.disease_cause ,Mice ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,FOLFOX ,Tumor Cells, Cultured ,Guanine Nucleotide Exchange Factors ,erbb negative regulator ,Mice, Knockout ,Clinical Trials as Topic ,Gastroenterology ,phase-iii trial ,Combination chemotherapy ,differentiation ,General Medicine ,Prognosis ,DNA-Binding Proteins ,ErbB Receptors ,k-ras ,030220 oncology & carcinogenesis ,Disease Progression ,FOLFIRI ,Biomarker (medicine) ,KRAS ,Drug therapy ,Colorectal Neoplasms ,Signal Transduction ,Research Article ,medicine.drug ,medicine.medical_specialty ,Primary Cell Culture ,Context (language use) ,Therapeutics ,acquired-resistance ,Disease-Free Survival ,03 medical and health sciences ,stem-cell marker ,1st-line treatment ,Spheroids, Cellular ,Internal medicine ,Biomarkers, Tumor ,medicine ,Animals ,Humans ,Cell Proliferation ,business.industry ,Tumor Suppressor Proteins ,Computational Biology ,medicine.disease ,digestive system diseases ,Clinical trial ,Disease Models, Animal ,030104 developmental biology ,cetuximab treatment ,business - Abstract
Colorectal cancer (CRC) is the third most frequent neoplastic disorder and is a main cause of tumor-related mortality as many patients progress to stage IV metastatic CRC. Standard care consists of combination chemotherapy (FOLFIRI or FOLFOX). Patients with WT KRAS typing are eligible to receive anti-EGFR therapy combined with chemotherapy. Unfortunately, predicting efficacy of CRC anti-EGFR therapy has remained challenging. Here we uncover that the EGFR-pathway component RasGRP1 acts as CRC tumor suppressor in the context of aberrant Wnt signaling. We find that RasGRP1 suppresses EGF-driven proliferation of colonic epithelial organoids. Having established that RasGRP1 dosage levels impacts biology, we focused on CRC patients next. Mining five different data platforms, we establish that RasGRP1 expression levels decrease with CRC progression and predict poor clinical outcome of patients. Lastly, deletion of one or two Rasgrp1 alleles makes CRC spheroids more susceptible to EGFR inhibition. Retrospective analysis of the CALGB80203 clinical trial shows that addition of anti-EGFR therapy to chemotherapy significantly improves outcome for CRC patients when tumors express low RasGRP1 suppressor levels. In sum, RasGRP1 is a unique biomarker positioned in the EGFR pathway and of potential relevance to anti-EGFR therapy for CRC patients. ispartof: JCI INSIGHT vol:4 issue:15 ispartof: location:United States status: published
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- 2019
42. Cryotherapy for liver metastases
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Liver Neoplasms [*secondary ,therapy] ,Adult ,Male ,CONTINUOUS REGIONAL CHEMOTHERAPY ,DEGRADABLE STARCH MICROSPHERES ,PHASE-III TRIAL ,HEPATIC ARTERIAL INFUSION ,DRUG-ELUTING BEADS ,QUALITY-OF-LIFE ,Humans ,Female ,PERCUTANEOUS ETHANOL INJECTION ,PROSPECTIVE RANDOMIZED-TRIAL ,Y-90 RESIN MICROSPHERES ,Cryotherapy [*methods] ,UNRESECTABLE HEPATOCELLULAR-CARCINOMA ,Randomized Controlled Trials as Topic - Abstract
BackgroundThe liver is affected by two of the most common groups of malignant tumours: primary liver tumours and liver metastases from colorectal carcinoma. Liver metastases are significantly more common than primary liver cancer and long-term survival rates reported for patients after radical surgical treatment is approximately 50%. However, R0 resection (resection for cure) is not feasible in the majority of patients. Cryotherapy is performed with the use of an image-guided cryoprobe which delivers liquid nitrogen or argon gas to the tumour tissue. The subsequent process of freezing is associated with formation of ice crystals, which directly damage exposed tissue, including cancer cells.ObjectivesTo assess the beneficial and harmful effects of cryotherapy compared with no intervention, other ablation methods, or systemic treatments in people with liver metastases.Search methodsWe searched The Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid, Embase Ovid, and six other databases up to June 2018.Selection criteriaRandomised clinical trials assessing beneficial and harmful effects of cryotherapy and its comparators for liver metastases, irrespective of the location of the primary tumour.Data collection and analysisWe used standard methodological procedures expected by Cochrane. We extracted information on participant characteristics, interventions, study outcomes, and data on the outcomes important for our review, as well as information on the design and methodology of the trials. Two review authors independently assessed risk of bias in each study. One review author performed data extraction and a second review author checked entries.Main resultsWe found no randomised clinical trials comparing cryotherapy versus no intervention or versus systemic treatments; however, we identified one randomised clinical trial comparing cryotherapy with conventional surgery. The trial was conducted in Ukraine. The trial included 123 participants with solitary, or multiple unilobar or bilobar liver metastases; 63 participants received cryotherapy and 60 received conventional surgery. There were 36 women and 87men. The primary sites for themetastases were colon and rectum (66.6%), stomach (7.3%), breast (6.5%), skin (4.9%), ovaries (4.1%), uterus (3.3%), kidney (3.3%), intestines (1.6%), pancreas (1.6%), and unknown (0.8%). The trial was not reported sufficiently enough to assess the risk of bias of the randomisation process, allocation concealment, or presence of blinding. It was also not possible to assess incomplete outcome data and selective outcome reporting bias. The certainty of evidence was low because of risk of bias and imprecision.The participants were followed for up to 10 years (minimum five months). The trial reported that the mortality at 10 years was 81% (51/63) in the cryotherapy group and 92%(55/60) in the conventional surgery group. The calculated by us relative risk (RR) with 95% Confidence Interval (CI) was: RR 0.88, 95% CI 0.77 to 1.02. We judged the evidence as low-certainty evidence. Regarding adverse events and complications, separately and in total, our calculation showed no evidence of a difference in recurrence of the malignancy in the liver: 86% (54/63) of the participants in the cryotherapy group and 95% (57/60) of the participants in the conventional surgery group developed a new malignancy (RR 0.90, 95% CI 0.80 to 1.01; low-certainty evidence). The frequency of reported complications was similar between the cryotherapy group and the conventional surgery group, except for postoperative pain. Both insignificant and pronounced pain were reported to be more common in the cryotherapy group while intense pain was reported to be more common in the conventional surgery group. However, the authors did not report whether there was any evidence of a difference. There were no intervention-related mortality or bile leakages.We identified no evidence for health-related quality of life, cancer mortality, or time to progression of liver metastases. The study reported tumour response in terms of the carcinoembryonic antigen level in 69% of participants, and reported results in the form of a graph for 30% of participants. The carcinoembryonic antigen level was lower in the cryotherapy group, and decreased to normal values faster in comparison with the control group (P Funding: the trial did not provide information on funding.Authors' conclusionsThe evidence for the effectiveness of cryotherapy versus conventional surgery in people with liver metastases is of low certainty. We are uncertain about our estimate and cannot determine whether cryotherapy compared with conventional surgery is beneficial or harmful. We found no evidence for the benefits or harms of cryotherapy compared with no intervention, or versus systemic treatments.
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- 2019
43. Systematic Review of Systemic Therapies and Therapeutic Combinations with Local Treatments for High-risk Localized Prostate Cancer
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Mary-Ellen Taplin, Antony Vincent D'amico, Christopher Sweeney, Fred Saad, Lorenzo Tosco, Mario A. Eisenberger, James A. Eastham, Martin E. Gleave, Alberto Briganti, Karim Fizazi, Karin Haustermans, Christopher J. Logothetis, Tosco, L., Briganti, A., D'Amico, A. V., Eastham, J., Eisenberger, M., Gleave, M., Haustermans, K., Logothetis, C. J., Saad, F., Sweeney, C., Taplin, M. -E., and Fizazi, K.
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Oncology ,Male ,medicine.medical_specialty ,Urology ,medicine.medical_treatment ,030232 urology & nephrology ,Cochrane Library ,10-YEAR FOLLOW-UP ,Adenocarcinoma ,law.invention ,Androgen deprivation therapy ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,RADIATION-THERAPY ,medicine ,ONCOLOGY-GROUP ,Humans ,Multimodality ,Prostatectomy ,LONG-TERM UPDATE ,Science & Technology ,Systemic therapy ,business.industry ,High risk ,RADICAL PROSTATECTOMY ,Prostatic Neoplasms ,PHASE-III TRIAL ,Urology & Nephrology ,medicine.disease ,Combined Modality Therapy ,RANDOMIZED-TRIAL ,Radiation therapy ,Systematic review ,Docetaxel ,030220 oncology & carcinogenesis ,ESTRAMUSTINE PHOSPHATE ,ANDROGEN-DEPRIVATION THERAPY ,business ,CHEMOHORMONAL THERAPY ,Life Sciences & Biomedicine ,medicine.drug - Abstract
Context: Systemic therapies, combined with local treatment for high-risk prostate cancer, are recommended by the international guidelines for specific subgroups of patients; however, for many of the clinical scenarios, it remains a research field. Objective: To perform a systematic review, and describe current evidence and perspectives about the multimodal treatment of high-risk prostate cancer. Evidence acquisition: We performed a systematic review of PubMED, Embase, Cochrane Library, European Society of Medical Oncology/American Society of Clinical Oncology Annual proceedings, and clinicalTrial.gov between January 2010 and February 2018 following the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. Evidence synthesis: Seventy-seven prospective trials were identified. According to multiple randomized trials, combining androgen deprivation therapy (ADT) with external-beam radiotherapy (EBRT) outperforms EBRT alone for both relapse-free and overall survival. Neoadjuvant ADT did not show significant improvement compared with prostatectomy alone. The role of adjuvant ADT after prostatectomy in patients with high-risk disease is still debated, with lack of data from phase 3 trials in pN0 patients. Novel androgen pathway inhibitors have been tested only in early-phase trials in addition to primary treatment. GETUG 12, RTOG 0521, and nonmetastatic subgroup of the STAMPEDE trial showed improved relapse-free survival for docetaxel in patients treated with EBRT plus ADT, although mature metastasis-free survival data are still pending. Both the SPCG-12 and the VACSP#553 trial showed no improvement in relapse-free survival for adjuvant docetaxel after prostatectomy. Conclusions: In contrast to the clearly demonstrated survival benefits of long-term adjuvant ADT when used with EBRT, its role after prostatectomy remains unclear especially in pN0 patients. Adding docetaxel to EBRT-ADT improves relapse-free survival, with immature results on overall survival. Novel androgen receptor pathway inhibitors are currently being tested in the neoadjuvant and adjuvant setting. Patient summary: Treatment of high-risk prostate cancer is based on a multimodality approach that includes systemic treatments. The best treatment or therapy combination remains to be defined. Androgen deprivation therapy improves overall survival when combined with radiotherapy, and such evidence is missing when the primary local treatment is radical prostatectomy. Docetaxel is associated with improved relapse-free survival in high-risk prostate cancer, but long-term follow-up is needed to assess its impact on survival. Bisphosphonates do not postpone the onset of bone metastases.
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- 2019
44. Systematic evaluation of the efficacy-effectiveness gap of systemic treatments in metastatic nonsmall cell lung cancer
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Cramer-van der Welle, Christine M., Peters, Bas J. M., Schramel, Franz M. N. H., Klungel, Olaf H., Groen, Harry J. M., van de Garde, Ewoudt M. W., Polman, A. J., van den Borne, B. E. E. M., van Putten, J. W. G., Smit, A. A. J., Termeer, A., Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Damage and Repair in Cancer Development and Cancer Treatment (DARE)
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Pulmonary and Respiratory Medicine ,Oncology ,Male ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,Targeted therapy ,03 medical and health sciences ,0302 clinical medicine ,MAINTENANCE BEVACIZUMAB ,Multicenter trial ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,PERFORMANCE STATUS ,Carcinoma ,medicine ,Humans ,GEMCITABINE PLUS CARBOPLATIN ,030212 general & internal medicine ,Registries ,Neoplasm Metastasis ,Aged ,Netherlands ,MULTICENTER TRIAL ,Chemotherapy ,Clinical Trials as Topic ,Performance status ,business.industry ,Lung Cancer ,Cancer ,PHASE-III TRIAL ,Original Articles ,Middle Aged ,CISPLATIN VS. GEMCITABINE ,medicine.disease ,OPEN-LABEL ,STAGE IIIB ,Discontinuation ,Clinical trial ,1ST-LINE TREATMENT ,Treatment Outcome ,COOPERATIVE-ONCOLOGY-GROUP ,030220 oncology & carcinogenesis ,Female ,business - Abstract
The divergence between clinical trial results and real-world outcomes is largely unknown for many cancer types. The present study aims overall to assess the efficacy–effectiveness gap (difference between outcomes in clinical trials and the real world) in systemic treatment for metastatic nonsmall cell lung cancer (NSCLC). All patients diagnosed with stage IV NSCLC between 2008 and 2014 within a network of seven Dutch large teaching hospitals (Santeon) were studied. For every patient, an efficacy–effectiveness (EE) factor was calculated by dividing individual patients' overall survival (OS) by the pooled median OS assessed from clinical trials with the respective treatment. From 2989 diagnosed patients, 1214 (41%) started with first-line treatment. For all studied regimens, real-world OS was shorter than OS reported in clinical trials. Overall, the EE factor was 0.77 (95% CI 0.70–0.85; p, Survival of patients with metastatic NSCLC treated with chemotherapy or targeted therapy in real-world practice is nearly one quarter shorter than for patients included in clinical trials. These real-world data provide useful information for clinicians. http://ow.ly/Khd230minFF
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- 2018
45. Ten-year results of the PORTEC-2 trial for high-intermediate risk endometrial carcinoma: improving patient selection for adjuvant therapy
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Wortman, B.G., Creutzberg, C.L., Putter, H., Jurgenliemk-Schulz, I.M., Jobsen, J.J., Lutgens, L.C.H.W., Steen-Banasik, E.M. van der, Mens, J.W.M., Slot, A., Kroese, M.C.S., Triest, B. van, Nijman, H.W., Stelloo, E., Bosse, T., Boer, S.M. de, Putten, W.L.J. van, Smit, V.T.H.B.M., Nout, R.A., PORTEC Study Grp, Translational Immunology Groningen (TRIGR), Targeted Gynaecologic Oncology (TARGON), and Radiotherapy
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0301 basic medicine ,Cancer Research ,medicine.medical_treatment ,Brachytherapy ,GYNECOLOGIC-ONCOLOGY-GROUP ,law.invention ,0302 clinical medicine ,Randomized controlled trial ,law ,QUALITY-OF-LIFE ,PROGNOSTIC-SIGNIFICANCE ,Clinical endpoint ,Radiotherapy Dosage ,PHASE-III TRIAL ,Middle Aged ,LYMPHVASCULAR SPACE INVOLVEMENT ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Vagina ,Female ,medicine.medical_specialty ,Urology ,OPERATIVE RADIATION-THERAPY ,Neural Cell Adhesion Molecule L1 ,Article ,Pelvis ,03 medical and health sciences ,medicine ,Adjuvant therapy ,Carcinoma ,Humans ,External beam radiotherapy ,Aged ,Neoplasm Staging ,business.industry ,Endometrial cancer ,Patient Selection ,medicine.disease ,Survival Analysis ,RANDOMIZED-TRIAL ,Endometrial Neoplasms ,Radiation therapy ,030104 developmental biology ,CANCER MRC ASTEC ,EXTERNAL-BEAM RADIOTHERAPY ,Radiotherapy, Adjuvant ,Tumor Suppressor Protein p53 ,business ,PELVIC RADIOTHERAPY - Abstract
BACKGROUND: PORTEC-2 was a randomised trial for women with high-intermediate risk (HIR) endometrial cancer, comparing pelvic external beam radiotherapy (EBRT) with vaginal brachytherapy (VBT). We evaluated long-term outcomes combined with the results of pathology review and molecular analysis.METHODS: 427 women with HIR endometrial cancer were randomised between 2002-2006 to VBT or EBRT. Primary endpoint was vaginal recurrence (VR). Pathology review was done in 97.4%, combined with molecular analysis.RESULTS: Median follow-up was 116 months; 10-year VR was 3.4% versus 2.4% for VBT vs. EBRT (p = 0.55). Ten-year pelvic recurrence (PR) was more frequent in the VBT group (6.3% vs. 0.9%, p = 0.004), mostly combined with distant metastases (DM). Tenyear isolated PR was 2.5% vs. 0.5%, p = 0.10, and DM 10.4 vs. 8.9% (p = 0.45). Overall survival for VBT vs. EBRT was 69.5% vs. 67.6% at 10 years (p = 0.72). L1CAM and p53-mutant expression and substantial lymph-vascular space invasion were risk factors for PR and DM. EBRT reduced PR in cases with these risk factors.CONCLUSION: Long-term results of the PORTEC-2 trial confirm VBT as standard adjuvant treatment for HIR endometrial cancer. Molecular risk assessment has the potential to guide adjuvant therapy. EBRT provided better pelvic control in patients with unfavourable risk factors.
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- 2018
46. Short Androgen Suppression and Radiation Dose Escalation for Intermediate- and High-Risk Localized Prostate Cancer
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Amit Bahl, Dirk Boehmer, Laurence Collette, Emad Shash, Christopher D Scrase, Laurette Renard, John Armstrong, Alphonsus C.M. van den Bergh, Salvador Villà, Christian Carrie, Bradley R. Pieters, Corneel Coens, Jean-François Bosset, Fernanda G. Herrera, Philippe Maingon, Santhanam Sundar, P. Kitsios, Elzbieta van der Steen-Banasik, Michel Bolla, Annerie Slot, Philip Poortmans, Rahamim Ben-Yosef, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,DURATION ,030232 urology & nephrology ,Urology ,Androgen suppression ,THERAPY ,law.invention ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Randomized controlled trial ,Prostate ,law ,QUALITY-OF-LIFE ,Clinical endpoint ,Medicine ,Humans ,DEPRIVATION ,RTOG ,Aged ,Gynecology ,Aged, 80 and over ,business.industry ,Cancer ,Prostatic Neoplasms ,Androgen Antagonists ,Radiotherapy Dosage ,PHASE-III TRIAL ,Middle Aged ,Prostate-Specific Antigen ,RANDOMIZED CONTROLLED-TRIAL ,medicine.disease ,ONCOLOGY ,Combined Modality Therapy ,Women's cancers Radboud Institute for Health Sciences [Radboudumc 17] ,Radiation therapy ,Prostate-specific antigen ,medicine.anatomical_structure ,Androgen Antagonists/therapeutic use ,Prostate-Specific Antigen/blood ,Prostatic Neoplasms/mortality ,Prostatic Neoplasms/therapy ,030220 oncology & carcinogenesis ,business ,RADIOTHERAPY - Abstract
Purpose Up to 30% of patients who undergo radiation for intermediate- or high-risk localized prostate cancer relapse biochemically within 5 years. We assessed if biochemical disease-free survival (DFS) is improved by adding 6 months of androgen suppression (AS; two injections of every-3-months depot of luteinizing hormone–releasing hormone agonist) to primary radiotherapy (RT) for intermediate- or high-risk localized prostate cancer. Patients and Methods A total of 819 patients staged: (1) cT1b-c, with prostate-specific antigen (PSA) ≥ 10 ng/mL or Gleason ≥ 7, or (2) cT2a (International Union Against Cancer TNM 1997), with no involvement of pelvic lymph nodes and no clinical evidence of metastatic spread, with PSA ≤ 50 ng/mL, were centrally randomized 1:1 to either RT or RT plus AS started on day 1 of RT. Centers opted for one dose (70, 74, or 78 Gy). Biochemical DFS, the primary end point, was defined from entry until PSA relapse (Phoenix criteria) and clinical relapse by imaging or death of any cause. The trial had 80% power to detect hazard ratio (HR), 0.714 by intent-to-treat analysis stratified by dose of RT at the two-sided α = 5%. Results The median patient age was 70 years. Among patients, 74.8% were intermediate risk and 24.8% were high risk. In the RT arm, 407 of 409 patients received RT; in the RT plus AS arm, 403 patients received RT plus AS and three patients received RT only. At 7.2 years median follow-up, RT plus AS significantly improved biochemical DFS (HR, 0.52; 95% CI, 0.41 to 0.66; P < .001, with 319 events), as well as clinical progression-free survival (205 events, HR, 0.63; 95% CI, 0.48 to 0.84; P = .001). In exploratory analysis, no statistically significant interaction between treatment effect and dose of RT could be evidenced (heterogeneity P = .79 and P = .66, for biochemical DFS and progression-free survival, respectively). Overall survival data are not mature yet. Conclusion Six months of concomitant and adjuvant AS improves biochemical and clinical DFS of intermediate- and high-risk cT1b-c to cT2a (with no involvement of pelvic lymph nodes and no clinical evidence of metastatic spread) prostatic carcinoma, treated by radiation.
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- 2016
47. Balancing treatment efficacy, toxicity and complication risk in elderly patients with metastatic renal cell carcinoma
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OLDER PATIENTS ,Angiogenesis inhibitors ,PHASE-III TRIAL ,CYTOREDUCTIVE NEPHRECTOMY ,RADICAL NEPHRECTOMY ,Programmed death 1 ,Nephrectomy ,Renal cell carcinoma ,RANDOMIZED-TRIAL ,DOUBLE-BLIND ,Elderly ,CANCER-TREATMENT TRIALS ,Immunotherapy ,EXPANDED ACCESS PROGRAM ,INTERFERON-ALPHA ,Mammalian target of rapamycin inhibitors ,CLINICAL-TRIALS - Abstract
The number of elderly patients with renal cell carcinoma is rising. Elderly patients differ from their younger counterparts in, among others, higher incidence of comorbidity and reduced organ function. Age influences outcome of surgery, and therefore has to be taken into account in elderly patients eligible for cytoreductive nephrectomy. Over the last decade several novel effective drugs have become available for the metastatic setting targeting angiogenesis and mammalian target of rapamycin. Immune checkpoint blockade with a programmed death 1 antibody has recently been shown to increase survival and further studies with immune checkpoint inhibitors are ongoing. In this review we summarize the available data on efficacy and toxicity of existing and emerging therapies for metastatic renal cell carcinoma in the elderly. Where possible, we provide evidence-based recommendations for treatment choices in elderly. (C) 2016 The Authors. Published by Elsevier Ltd.
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- 2016
48. VEGF pathway targeting agents, vessel normalization and tumor drug uptake
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METASTATIC COLORECTAL-CANCER ,DOUBLE-BLIND ,1ST-LINE TREATMENT ,GROWTH-FACTOR ,blood vessel normalization ,ANTIANGIOGENIC THERAPY ,CELL LUNG-CANCER ,BREAST-CANCER ,PHASE-III TRIAL ,antiangiogenic drugs ,tumor drug delivery ,NEWLY-DIAGNOSED GLIOBLASTOMA ,VASCULAR NORMALIZATION - Abstract
Vascular endothelial growth factor (VEGF) pathway targeting agents have been combined with other anticancer drugs, leading to improved efficacy in carcinoma of the cervix, stomach, lung, colon and rectum, ovary, and breast. Vessel normalization induced by VEGF pathway targeting agents influences tumor drug uptake. Following bevacizumab treatment, preclinical and clinical studies have shown a decrease in tumor delivery of radiolabeled antibodies and two chemotherapeutic drugs. The decrease in vessel pore size during vessel normalization might explain the decrease in tumor drug uptake. Moreover, the addition of bevacizumab to cetuximab, or panitumumab in colorectal cancer patients or to trastuzumab in breast cancer patients, did not improve efficacy. However, combining bevacizumab with chemotherapy did increase efficacy in some cancer types. Novel biomarkers to select patients who may benefit from combination therapies, such as the effect of an angiogenesis inhibitor on tumor perfusion, requires innovative trial designs and large clinical trials. Small imaging studies with radiolabeled drugs could be used in the interphase to gain further insight into the interplay between VEGF targeted therapy, vessel normalization and tumor drug delivery.
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- 2016
49. Molecular imaging in ovarian cancer
- Author
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K. E. Broekman, An K.L. Reyners, Adrienne H. Brouwers, Andor W. J. M. Glaudemans, H.J.G. Arts, Mathilde Jalving, van der Ate Zee, de Elisabeth G. E. Vries, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Targeted Gynaecologic Oncology (TARGON), Translational Immunology Groningen (TRIGR), and Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE)
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Oncology ,medicine.medical_specialty ,Pathology ,RECURRENT EPITHELIAL OVARIAN ,GROWTH-FACTOR ,medicine.medical_treatment ,TUMOR HETEROGENEITY ,Disease ,ANTIANGIOGENIC TREATMENT ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,POSITRON-EMISSION-TOMOGRAPHY ,Growth factor receptor ,Fluorodeoxyglucose F18 ,Internal medicine ,medicine ,Medical imaging ,Biomarkers, Tumor ,ZR-89-BEVACIZUMAB PET ,Animals ,Humans ,Tissue Distribution ,ESTROGEN-RECEPTOR EXPRESSION ,Ovarian Neoplasms ,medicine.diagnostic_test ,business.industry ,PRIMARY PERITONEAL ,PHASE-III TRIAL ,Hematology ,Immunotherapy ,medicine.disease ,molecular imaging ,F-18-FDG PET/CT ,ovarian cancer ,PET ,Positron emission tomography ,Hormone receptor ,030220 oncology & carcinogenesis ,Positron-Emission Tomography ,Female ,Molecular imaging ,Ovarian cancer ,business - Abstract
Ovarian cancer has a high mortality and novel-targeted treatment strategies have not resulted in breakthroughs for this disease. Insight into the molecular characteristics of ovarian tumors may improve diagnosis and selection of patients for treatment with targeted therapies. A potential way to achieve this is by means of molecular imaging. Generic tumor processes, such as glucose metabolism (F-18-fluorodeoxyglucose) and DNA synthesis (F-18-fluorodeoxythymidine), can be visualized non-invasively. More specific targets, such as hormone receptors, growth factor receptors, growth factors and targets of immunotherapy, can also be visualized. Molecular imaging can capture data on intra-patient tumor heterogeneity and is of potential value for individualized, target-guided treatment selection. Early changes in molecular characteristics during therapy may serve as early predictors of response. In this review, we describe the current knowledge on molecular imaging in the diagnosis and as an upfront or early predictive biomarker in patients with ovarian cancer.
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- 2016
50. Aromatase inhibitors versus tamoxifen in early breast cancer
- Author
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Dowsett, M, Forbes, JF, Bradley, R, Ingle, J, Aihara, T, Bliss, J, Boccardo, F, Coates, A, Coombes, RC, Cuzick, J, Dubsky, P, Gnant, M, Kaufmann, M, Kilburn, L, Perrone, F, Rea, D, Thuerlimann, B, Van de Velde, C, Pan, H, Peto, R, Davies, C, Gray, R, Baum, M, Buzdar, A, Sestak, I, Markopoulos, C, Fesl, C, Jakesz, R, Colleoni, M, Gelber, R, Regan, M, Von Minckwitz, G, Snowdon, C, Goss, P, Pritchard, K, Anderson, S, Costantino, J, Mamounas, E, Ohashi, Y, Watanabe, T, Bastiaannet, E, Interne Geneeskunde, Other departments, CCA -Cancer Center Amsterdam, Radiotherapy, Dowsett, M, Forbes, J. F, Bradley, R, Ingle, J, Aihara, T, Bliss, J, Boccardo, F, Coates, A, Coombes, R. C, Cuzick, J, Dubsky, P, Gnant, M, Kaufmann, M, Kilburn, L, Perrone, F, Rea, D, Thürlimann, B, van de Velde, C, Pan, H, Peto, R, Davies, C, Gray, R, DE LAURENTIIS, Michelino, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
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Oncology ,chemistry.chemical_compound ,Exemestane ,Aromatase ,skin and connective tissue diseases ,Randomized Controlled Trials as Topic ,AUSTRIAN BREAST ,biology ,Aromatase Inhibitors ,Medicine (all) ,Incidence (epidemiology) ,Letrozole ,PHASE-III TRIAL ,11 Medical And Health Sciences ,General Medicine ,POSTMENOPAUSAL WOMEN ,Female ,BONE-MINERAL DENSITY ,Life Sciences & Biomedicine ,Breast Neoplasm ,Human ,medicine.drug ,medicine.medical_specialty ,Antineoplastic Agents, Hormonal ,EXEMESTANE ,medicine.drug_class ,Early Breast Cancer Trialists' Collaborative Group (EBCTCG) ,Anastrozole ,Breast Neoplasms ,LETROZOLE ,Drug Administration Schedule ,ANASTROZOLE ,Medicine, General & Internal ,Breast cancer ,SDG 3 - Good Health and Well-being ,General & Internal Medicine ,Internal medicine ,medicine ,Aromatase Inhibitor ,Humans ,CONTINUED TAMOXIFEN ,Gynecology ,Science & Technology ,Aromatase inhibitor ,BIG 1-98 ,business.industry ,medicine.disease ,LONG ,Tamoxifen ,chemistry ,biology.protein ,ADJUVANT ENDOCRINE THERAPY ,business - Abstract
Background The optimal ways of using aromatase inhibitors or tamoxifen as endocrine treatment for early breast cancer remains uncertain.Methods We undertook meta-analyses of individual data on 31 920 postmenopausal women with oestrogen-receptor-positive early breast cancer in the randomised trials of 5 years of aromatase inhibitor versus 5 years of tamoxifen; of 5 years of aromatase inhibitor versus 2-3 years of tamoxifen then aromatase inhibitor to year 5; and of 2-3 years of tamoxifen then aromatase inhibitor to year 5 versus 5 years of tamoxifen. Primary outcomes were any recurrence of breast cancer, breast cancer mortality, death without recurrence, and all-cause mortality. Intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded aromatase inhibitor versus tamoxifen first-event rate ratios (RRs).Findings In the comparison of 5 years of aromatase inhibitor versus 5 years of tamoxifen, recurrence RRs favoured aromatase inhibitors significantly during years 0-1 (RR 0.64, 95% CI 0.52-0.78) and 2-4 (RR 0.80, 0.68-0.93), and non-significantly thereafter. 10-year breast cancer mortality was lower with aromatase inhibitors than tamoxifen (12.1% vs 14.2%; RR 0.85, 0.75-0.96; 2p=0.009). In the comparison of 5 years of aromatase inhibitor versus 2-3 years of tamoxifen then aromatase inhibitor to year 5, recurrence RRs favoured aromatase inhibitors significantly during years 0-1 (RR 0.74, 0.62-0.89) but not while both groups received aromatase inhibitors during years 2-4, or thereafter; overall in these trials, there were fewer recurrences with 5 years of aromatase inhibitors than with tamoxifen then aromatase inhibitors (RR 0.90, 0.81-0.99; 2p=0.045), though the breast cancer mortality reduction was not significant (RR 0.89, 0.78-1.03; 2p=0.11). In the comparison of 2-3 years of tamoxifen then aromatase inhibitor to year 5 versus 5 years of tamoxifen, recurrence RRs favoured aromatase inhibitors significantly during years 2-4 (RR 0.56, 0.46-0.67) but not subsequently, and 10-year breast cancer mortality was lower with switching to aromatase inhibitors than with remaining on tamoxifen (8.7% vs 10.1%; 2p=0.015). Aggregating all three types of comparison, recurrence RRs favoured aromatase inhibitors during periods when treatments differed (RR 0.70, 0.64-0.77), but not significantly thereafter (RR 0.93, 0.86-1.01; 2p=0.08). Breast cancer mortality was reduced both while treatments differed (RR 0.79, 0.67-0.92), and subsequently (RR 0.89, 0.81-0.99), and for all periods combined (RR 0.86, 0.80-0.94; 2p=0.0005). All-cause mortality was also reduced (RR 0.88, 0.82-0.94; 2p=0.0003). RRs differed little by age, body-mass index, stage, grade, progesterone receptor status, or HER2 status. There were fewer endometrial cancers with aromatase inhibitors than tamoxifen (10-year incidence 0.4% vs 1.2%; RR 0.33, 0.21-0.51) but more bone fractures (5-year risk 8.2% vs 5.5%; RR 1.42, 1.28-1.57); non-breast-cancer mortality was similar.Interpretation Aromatase inhibitors reduce recurrence rates by about 30% (proportionately) compared with tamoxifen while treatments diff er, but not thereafter. 5 years of an aromatase inhibitor reduces 10-year breast cancer mortality rates by about 15% compared with 5 years of tamoxifen, hence by about 40% (proportionately) compared with no endocrine treatment. Copyright (C) Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Open Access article distributed under the terms of CC BY.
- Published
- 2015
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