77 results on '"RANDOMIZED PHASE-III"'
Search Results
2. European consensus-based interdisciplinary guideline for melanoma. Part 2
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POSTOPERATIVE STEREOTACTIC RADIOSURGERY ,LENTIGO MALIGNA MELANOMA ,MOHS MICROGRAPHIC SURGERY ,Metastasectomy ,Sentinel lymph node dissection ,Interferon-alpha ,Systemic treatment ,Adjuvant treatment ,RANDOMIZED PHASE-III ,Tumor thickness ,SURGICAL EXCISION MARGINS ,HIGH-RISK MELANOMA ,PRIMARY CUTANEOUS MELANOMA ,STAGE IV MELANOMA ,Excisional margins ,Cutaneous melanoma ,SENTINEL-NODE BIOPSY ,DABRAFENIB PLUS TRAMETINIB - Abstract
A unique collaboration of multidisciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on cutaneous melanoma diagnosis and treatment, based on the systematic literature reviews and the experts' experience. Cutaneous melanomas are excised with one to 2-cm safety margins. Sentinel lymph node dissection shall be performed as a staging procedure in patients with tumor thickness ≥1.0 mm or ≥0.8 mm with additional histological risk factors, although there is as yet no clear survival benefit for this approach. Therapeutic decisions in stage III/IV patients should be primarily made by an interdisciplinary oncology team ("tumor board"). Adjuvant therapies can be proposed in stage III/completely resected stage IV patients and are primarily anti-PD-1, independent of mutational status, or alternatively dabrafenib plus trametinib for BRAF mutant patients. In distant metastases (stage IV), either resected or not, systemic treatment is always indicated. For first-line treatment particularly in BRAF wild-type patients, immunotherapy with PD-1 antibodies alone or in combination with CTLA-4 antibodies shall be considered. In stage IV melanoma with a BRAF-V600 E/K mutation, first-line therapy with BRAF/MEK inhibitors can be offered as an alternative to immunotherapy. In patients with primary resistance to immunotherapy and harboring a BRAF-V600 E/K mutation, this therapy shall be offered as second-line therapy. Systemic therapy in stage III/IV melanoma is a rapidly changing landscape, and it is likely that these recommendations may change in the near future.
- Published
- 2022
3. The effectiveness of gamma knife radiosurgery for the management of residual high-grade gliomas: A single institutional study
- Author
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Fatih Yakar, Emrah Egemen, Ümit A Dere, Halil Sağınç, Ulaş Gökdeniz, Batuhan Bakırarar, Ceyda G Gökdeniz, Bahar Baltalarlı, Mehmet E Coşkun, and Feridun Acar
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Glioblastoma-Multiforme ,Radiotherapy ,Survival ,Brain Neoplasms ,Randomized Phase-Iii ,Stereotactic Radiosurgery ,Glioma ,General Medicine ,Radiosurgery ,Central-Nervous-System ,Progression-Free Survival ,Treatment Outcome ,Neurology ,Physiology (medical) ,Primary Brain ,Humans ,Adjuvant Temozolomide ,Surgery ,Neurology (clinical) ,Malignant Gliomas ,Glioblastoma ,Tumors ,Follow-Up Studies ,Retrospective Studies - Abstract
High-grade gliomas (HGGs) are presently managed via surgical resection, external beam radiation therapy (EBRT), and chemotherapy. Although Gamma Knife radiosurgery (GKRS) is currently used to manage HGGs, it has not been considered standard care. This paper aims to compare the contribution of GKRS to clinical outcomes in patients in which gross total resection (GTR) cannot be achieved. We retrospectively reviewed the data of 99 patients with HGG (World Health Organization (WHO) grade III and IV) from two groups: group 1 consisted of 68 patients for which only EBRT was administered, and group 2 consisted of 31 patients for which EBRT and GKRS were administered. Patient demographic data, the extent of resection, IDH mutation, radiation dosage, progression-free survival (PFS), overall survival (OS), and follow-up time were recorded and compared across groups. The grade III/IV tumor ratio was 10/58 and 10/21 in groups 1 and 2, respectively. In group 2, PFS and OS were higher than in group 1 (P = 0.030 and 0.021). The mean follow-up time was 15.02 +/- 11.8 (3-52) and 18.9 +/- 98.6 (7-43) months in groups 1 and 2, respectively. In addition to the standard management of HGGs in patients without GTR, boost GKRS during the early postoperative period is beneficial for increasing PFS and OS. (c) 2021 Published by Elsevier Ltd.
- Published
- 2022
4. Improved response rate in patients with prognostically poor locally advanced rectal cancer after treatment with induction chemotherapy and chemoradiotherapy when compared with chemoradiotherapy alone: A matched case-control study
- Author
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J. Willems, E.L.K. Voogt, J. Nederend, Jacobus W. A. Burger, G. van Lijnschoten, G.A.P. Nieuwenhuijzen, Dennis P. Schaap, H.J.T. Rutten, G.J.M. Creemers, H.M.U. Peulen, K. van den Berg, J. S. Cnossen, J.G. Bloemen, Surgery, and RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy
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Male ,Oncology ,Organoplatinum Compounds ,Colorectal cancer ,medicine.medical_treatment ,Leucovorin ,030230 surgery ,CHEMORADIATION ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,DISEASE-FREE SURVIVAL ,Fascia ,Lymph node ,Locally advanced rectal cancer ,Response rate (survey) ,Chemoradiotherapy ,Induction Chemotherapy ,General Medicine ,Prognosis ,Magnetic Resonance Imaging ,Total mesorectal excision ,Neoadjuvant Therapy ,Tumor Burden ,Bevacizumab ,Oxaliplatin ,Treatment Outcome ,medicine.anatomical_structure ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,Cohort ,Female ,Fluorouracil ,medicine.medical_specialty ,Total neoadjuvant therapy ,03 medical and health sciences ,Internal medicine ,parasitic diseases ,medicine ,Humans ,Neoplasm Invasiveness ,Watchful Waiting ,EXTRAMURAL VASCULAR INVASION ,Capecitabine ,Response Evaluation Criteria in Solid Tumors ,PREOPERATIVE RADIOTHERAPY ,Aged ,Neoplasm Staging ,Retrospective Studies ,Pathological complete response ,Rectal Neoplasms ,business.industry ,TOTAL MESORECTAL EXCISION ,Induction chemotherapy ,RANDOMIZED PHASE-III ,NEOADJUVANT CHEMORADIOTHERAPY ,medicine.disease ,Clinical complete response ,Radiation therapy ,Case-Control Studies ,Surgery ,Dose Fractionation, Radiation ,FOLLOW-UP ,business - Abstract
Introduction: The addition of induction chemotherapy (ICT) to neoadjuvant chemoradiotherapy (CRT) has the potential to improve outcomes in patients with locally advanced rectal cancer (LARC). However, patient selection is essential to prevent overtreatment. This study compared the complete response (CR) rate after treatment with and without ICT of LARC patients with prognostically poor characteristics. Methods: All LARC patients who were treated with neoadjuvant CRT, whether or not preceded by ICT, and who underwent surgery or were considered for a wait-and-see strategy between January 2016 and March 2020 in the Catharina Hospital Eindhoven, were retrospectively selected. LARC was defined as any T4 tumour, or a T2/T3 tumour with extramural venous invasion and/or tumour deposits and/or N2 lymph node status, and/or mesorectal fascia involvement (T3 tumours only). Case-control matching was per -formed based on the aforementioned characteristics. Results: Of 242 patients, 178 (74%) received CRT (CRT-group) and 64 patients (26%) received ICT followed by CRT (ICT-group). In the ICT-group, 3 patients (5%) did not receive the minimum of three cycles. In addition, in this selected cohort, compliance with radiotherapy was 100% in the ICT-group and 97% in the CRT-group. The CR rate was 30% in the ICT-group and 15% in the CRT-group (p = 0.011). After case-control matching, the CR rate was 28% and 9%, respectively (p = 0.013). Conclusion: Treatment including ICT seemed well tolerated and resulted in a high CR rate. Hence, this treatment strategy may facilitate organ preservation and improve survival in LARC patients with prog-nostically poor characteristics. (c) 2021 Elsevier Ltd, BASO -The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.
- Published
- 2021
5. European consensus-based interdisciplinary guideline for melanoma. Part 2: Treatment - Update 2022
- Author
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Garbe, Claus, Amaral, Teresa, Peris, Ketty, Hauschild, Axel, Arenberger, Petr, Basset-Seguin, Nicole, Bastholt, Lars, Bataille, Veronique, Del Marmol, Veronique, Dréno, Brigitte, Fargnoli, Maria C, Forsea, Ana-Maria, Grob, Jean-Jacques, Hoeller, Christoph, Kaufmann, Roland, Kelleners-Smeets, Nicole, Lallas, Aimilios, Lebbé, Celeste, Lytvynenko, Bodhan, Malvehy, Josep, Moreno-Ramirez, David, Nathan, Paul, Pellacani, Giovanni, Saiag, Philippe, Stratigos, Alexander J, Van Akkooi, Alexander C J, Vieira, Ricardo, Zalaudek, Iris, Lorigan, Paul, European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organization for Research and Treatment of Cancer (EORTC), Garbe, Clau, Amaral, Teresa, Peris, Ketty, Hauschild, Axel, Arenberger, Petr, Basset-Seguin, Nicole, Bastholt, Lar, Bataille, Veronique, Del Marmol, Veronique, Dréno, Brigitte, Fargnoli, Maria C, Forsea, Ana-Maria, Grob, Jean-Jacque, Hoeller, Christoph, Kaufmann, Roland, Kelleners-Smeets, Nicole, Lallas, Aimilio, Lebbé, Celeste, Lytvynenko, Bodhan, Malvehy, Josep, Moreno-Ramirez, David, Nathan, Paul, Pellacani, Giovanni, Saiag, Philippe, Stratigos, Alexander J, Van Akkooi, Alexander C J, Vieira, Ricardo, Zalaudek, Iri, and Lorigan, Paul
- Subjects
Proto-Oncogene Proteins B-raf ,Cancer Research ,Consensus ,Skin Neoplasms ,Consensu ,Systemic treatment ,Oxime ,HIGH-RISK MELANOMA ,Antineoplastic Combined Chemotherapy Protocols ,Oximes ,Humans ,Excisional margins ,Melanoma ,SENTINEL-NODE BIOPSY ,Tumor thickne ,Neoplasm Staging ,POSTOPERATIVE STEREOTACTIC RADIOSURGERY ,LENTIGO MALIGNA MELANOMA ,Antineoplastic Combined Chemotherapy Protocol ,Manchester Cancer Research Centre ,ResearchInstitutes_Networks_Beacons/mcrc ,MOHS MICROGRAPHIC SURGERY ,Metastasectomy ,Sentinel lymph node dissection ,Interferon-alpha ,RANDOMIZED PHASE-III ,Adjuvant treatment ,Tumor thickness ,Cutaneous melanoma ,Interferon-α ,Mutation ,Systematic Reviews as Topic ,SURGICAL EXCISION MARGINS ,Oncology ,PRIMARY CUTANEOUS MELANOMA ,STAGE IV MELANOMA ,Excisional margin ,Settore MED/35 - MALATTIE CUTANEE E VENEREE ,DABRAFENIB PLUS TRAMETINIB ,Human - Abstract
A unique collaboration of multidisciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on cutaneous melanoma diagnosis and treatment, based on the systematic literature reviews and the experts' experience. Cutaneous melanomas are excised with one to 2-cm safety margins. Sentinel lymph node dissection shall be performed as a staging procedure in patients with tumor thickness ≥1.0mm or ≥0.8mm with additional histological risk factors, although there is as yet no clear survival benefit for this approach. Therapeutic decisions in stage III/IV patients should be primarily made by an interdisciplinary oncology team ("tumor board"). Adjuvant therapies can be proposed in stage III/completely resected stage IV patients and are primarily anti-PD-1, independent of mutational status, or alternatively dabrafenib plus trametinib for BRAF mutant patients. In distant metastases (stage IV), either resected or not, systemic treatment is always indicated. For first-line treatment particularly in BRAF wild-type patients, immunotherapy with PD-1 antibodies alone or in combination with CTLA-4 antibodies shall be considered. In stage IV melanoma with a BRAF-V600E/K mutation, first-line therapy with BRAF/MEK inhibitors can be offered as an alternative to immunotherapy. In patients with primary resistance to immunotherapy and harboring a BRAF-V600E/K mutation, this therapy shall be offered as second-line therapy. Systemic therapy in stage III/IV melanoma is a rapidly changing landscape, and it is likely that these recommendations may change in the near future.
- Published
- 2022
6. Venetoclax combinations delay the time to deterioration of HRQoL in unfit patients with acute myeloid leukemia
- Author
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Keith W. Pratz, Panayiotis Panayiotidis, Christian Recher, Xudong Wei, Brian A. Jonas, Pau Montesinos, Vladimir Ivanov, Andre C. Schuh, Courtney D. DiNardo, Jan Novak, Vlatko Pejsa, Don Stevens, Su-Peng Yeh, Inho Kim, Mehmet Turgut, Nicola Fracchiolla, Kazuhito Yamamoto, Yishai Ofran, Andrew H. Wei, Cat N. Bui, Katy Benjamin, Rajesh Kamalakar, Jalaja Potluri, Wellington Mendes, Jacob Devine, and Walter Fiedler
- Subjects
Myeloid ,Leukemia, Myeloid, Acute / etiology ,Cytarabine / therapeutic use ,Oncology and Carcinogenesis ,EUROPEAN-ORGANIZATION ,RISK MYELODYSPLASTIC SYNDROME ,Acute ,Cardiorespiratory Medicine and Haematology ,Bridged Bicyclo Compounds ,Rare Diseases ,QUALITY-OF-LIFE ,Clinical Research ,SUPPORTIVE CARE ,Antineoplastic Combined Chemotherapy Protocols ,Antineoplastic Combined Chemotherapy Protocols / adverse effects ,Humans ,REPORTED OUTCOMES ,ELDERLY-PATIENTS ,Fatigue ,Cancer ,Sulfonamides ,Leukemia ,OLDER PATIENTS ,Heterocyclic ,Cytarabine ,Hematology ,RANDOMIZED PHASE-III ,Bridged Bicyclo Compounds, Heterocyclic ,CONTROLLED-TRIALS ,LOW-DOSE CYTARABINE ,Leukemia, Myeloid, Acute ,Fatigue / etiology ,Oncology ,Quality of Life ,Leukemia, Myeloid, Acute / drug therapy - Abstract
Phase 3 trials Viale-A and Viale-C evaluated health-related quality of life (HRQoL) in patients with AML unfit for intensive chemotherapy who received venetoclax (VEN) + (AZA) (Viale-A) or low-dose cytarabine (LDAC) (Viale-C) or placebo (PBO) + AZA or LDAC. Patient-reported outcomes included: EORTC QLQ-C30 global health status (GHS/QoL) and physical functioning (PF), PROMIS Cancer Fatigue Short Form 7a (Fatigue), and EQ-5D-5L health status visual analog scale (HS-VAS). Time to deterioration (TTD), defined as worsening from baseline in meaningful change thresholds (MCT) of ≥10, 5, or 7 points for GHS/QoL or PF, fatigue, and HS-VAS, respectively, was assessed; differences between groups were analyzed using Kaplan-Meier and unadjusted log-rank analyses. VEN + AZA vs PBO + AZA patients had longer TTD in GHS/QoL (P = 0.066) and fatigue (P = 0.189), and significantly longer TTD in PF (P = 0.028) and HS-VAS (P P = 0.011), PF (P = 0.020), and fatigue (P = 0.004), and a trend in HS-VAS (P = 0.057). Approximately 43%, 35%, 32%, and 18% of patients treated with VEN + AZA, AZA + PBO, VEN + LDAC, or LDAC + PBO, respectively, saw improvements >MCT in GHS/QoL. Overall, VEN may positively impact HRQoL in patients with AML ineligible for intensive chemotherapy, leading to longer preservation of functioning and overall health status.
- Published
- 2022
7. Systemic Inflammation Response Index Predicts Survival Outcomes in Glioblastoma Multiforme Patients Treated with Standard Stupp Protocol
- Author
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Berrin Pehlivan, Duygu Sezen, Yurday Ozdemir, Ahmet Kucuk, Erkan Topkan, Huseyin Mertsoylu, Ali Ayberk Besen, Ugur Selek, Yasemin Bolukbasi, Sezen, Duygu (ORCID 0000-0002-4505-2280 & YÖK ID 170535), Bölükbaşı, Yasemin (ORCID 0000-0002-3170-5826 & YÖK ID 216814), Selek, Uğur (ORCID 0000-0001-8087-3140 & YÖK ID 27211), Topkan, Erkan, Küçük, Ahmet, Özdemir, Yurday, Mertsoylu, Hüseyin, Besen, Ali Ayberk, Pehlivan, Berrin, and School of Medicine
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Article Subject ,Medicine ,Immunology ,Systemic inflammation ,Severity of Illness Index ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Immunology and Allergy ,Aged ,Aged, 80 and over ,Inflammation ,Temozolomide ,Receiver operating characteristic ,Proportional hazards model ,business.industry ,Area under the curve ,Randomized phase-III ,T-cell infiltration ,Adjuvant temozolomide ,SIRI ,Radiotherapy ,Concomitant ,Neutrophil ,Prognosis ,Carcinoma ,Cancer ,General Medicine ,RC581-607 ,Middle Aged ,medicine.disease ,Treatment Outcome ,ROC Curve ,030220 oncology & carcinogenesis ,Retreatment ,Cohort ,Population study ,Female ,Immunologic diseases. Allergy ,medicine.symptom ,Glioblastoma ,business ,030217 neurology & neurosurgery ,Research Article ,medicine.drug - Abstract
Objectives: we endeavored to retrospectively assess the prognostic merit of pretreatment systemic immune response index (SIRI) in glioblastoma multiforme (GBM) patients who underwent postoperative partial brain radiotherapy (RT) and concurrent plus adjuvant temozolomide (TMZ), namely, the Stupp protocol. Methods: the records of 181 newly diagnosed GBM patients who received the postoperative Stupp protocol were retrospectively analyzed. The SIRI value for each eligible patient was calculated by utilizing the platelet, neutrophil, and lymphocyte measures obtained on the first day of treatment: SIRI=NeutrophilsxMonocytes/Lymphocytes. The ideal cutoff values for SIRI connected with the progression-free- (PFS) and overall survival (OS) results were methodically searched through using the receiver operating characteristic (ROC) curve analysis. Primary and secondary end-points constituted the potential OS and PFS distinctions among the SIRI groups, respectively. Results: the ROC curve analysis labeled the ideal SIRI cutoffs at 1.74 (Area under the curve (AUC): 74.9%; sensitivity: 74.2%; specificity: 71.4%) and 1.78 (AUC: 73.6%; sensitivity: 73.1%; specificity: 70.8%) for PFS and OS status, individually. The SIRI cutoff of 1.78 of the OS status was chosen as the common cutoff for the stratification of the study population (Group 1: SIRI 1.78 (N=85)) and further comparative PFS and OS analyses. Comparisons between the two SIRI cohorts manifested that the SIRI 1.78 counterparts. The results of multivariate Cox regression analyses ratified the independent and significant alliance between a low SIRI and longer PFS (P, NA
- Published
- 2020
8. Recent Advances of Immune Checkpoint Inhibition and Potential for (Combined) TIGIT Blockade as a New Strategy for Malignant Pleural Mesothelioma
- Author
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Sophie Rovers, Annelies Janssens, Jo Raskin, Patrick Pauwels, Jan P. van Meerbeeck, Evelien Smits, Elly Marcq, Faculty of Economic and Social Sciences and Solvay Business School, and Cellular and Molecular Immunology
- Subjects
PD-L1 ,Biochemistry & Molecular Biology ,TIGIT ,MULTICENTER ,Medicine (miscellaneous) ,Research & Experimental Medicine ,General Biochemistry, Genetics and Molecular Biology ,CISPLATIN ,FUTURE ,Pharmacology & Pharmacy ,PEMBROLIZUMAB ,COMBINATION ,Biology ,Science & Technology ,cancer immunotherapy ,Pharmacology. Therapy ,immune checkpoint blockade ,RANDOMIZED PHASE-III ,CHEMOTHERAPY ,OPEN-LABEL ,Chemistry ,Medicine, Research & Experimental ,mesothelioma ,NIVOLUMAB PLUS IPILIMUMAB ,TRIAL ,Human medicine ,Life Sciences & Biomedicine - Abstract
Malignant pleural mesothelioma (MPM) is a fatal cancer type that affects the membranes lining the lungs, and is causally associated with asbestos exposure. Until recently, the first-line treatment consisted of a combination of chemotherapeutics that only had a limited impact on survival, and had not been improved in decades. With the recent approval of combined immune checkpoint inhibition for MPM, promising new immunotherapeutic strategies are now emerging for this disease. In this review, we describe the current preclinical and clinical evidence of various immune checkpoint inhibitors in MPM. We will consider the advantages of combined immune checkpoint blockade in comparison with single agent checkpoint inhibitor drugs. Furthermore, recent evidence suggests a role for T cell immunoglobulin and ITIM domain (TIGIT), an inhibitory immunoreceptor, as a novel target for immunotherapy. As this novel immune checkpoint remains largely unexplored in mesothelioma, we will discuss the potential of TIGIT blockade as an alternative therapeutic approach for MPM. This review will emphasize the necessity for new and improved treatments for MPM, while highlighting the recent advances and future perspectives of combined immune checkpoint blockade, particularly aimed at PD-L1 and TIGIT. ispartof: BIOMEDICINES vol:10 issue:3 ispartof: location:Switzerland status: published
- Published
- 2022
9. Outcome measures in multimodal rectal cancer trials
- Subjects
QUALITY-OF-LIFE ,TOTAL MESORECTAL EXCISION ,DISEASE-FREE SURVIVAL ,SHORT-COURSE RADIOTHERAPY ,LOCAL RECURRENCE ,RANDOMIZED PHASE-III ,FOLLOW-UP ,SURROGATE END-POINTS ,POSTOPERATIVE CHEMORADIOTHERAPY ,PREOPERATIVE RADIOTHERAPY - Abstract
There is a large variability regarding the definition and choice of primary endpoints in phase 2 and phase 3 multimodal rectal cancer trials, resulting in inconsistency and difficulty of data interpretation. Also, surrogate properties of early and intermediate endpoints have not been systematically assessed. We provide a comprehensive review of clinical and surrogate endpoints used in trials for non-metastatic rectal cancer. The applicability, advantages, and disadvantages of these endpoints are summarised, with recommendations on clinical endpoints for the different phase trials, including limited surgery or non-operative management for organ preservation. We discuss how early and intermediate endpoints, including patient-reported outcomes and involvement of patients in decision making, can be used to guide trial design and facilitate consistency in reporting trial results in rectal cancer.
- Published
- 2020
10. Outcome measures in multimodal rectal cancer trials
- Author
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Karin Haustermans, Geerard L. Beets, David Sebag-Montefiore, Vincenzo Valentini, Marc Buyse, Bruce D. Minsky, Regina G. H. Beets-Tan, Julio Garcia-Aguilar, Phil Quirke, Ane L Appelt, Emmanouil Fokas, Rob Glynne-Jones, Ethan B. Ludmir, Claus Rödel, Maria Antonietta Gambacorta, and Corrie A.M. Marijnen
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Research design ,medicine.medical_specialty ,Time Factors ,Endpoint Determination ,Colorectal cancer ,MEDLINE ,LOCAL RECURRENCE ,03 medical and health sciences ,0302 clinical medicine ,QUALITY-OF-LIFE ,Clinical endpoint ,DISEASE-FREE SURVIVAL ,Humans ,Combined Modality Therapy ,Medicine ,SHORT-COURSE RADIOTHERAPY ,Patient Reported Outcome Measures ,Intensive care medicine ,PREOPERATIVE RADIOTHERAPY ,Settore MED/36 - DIAGNOSTICA PER IMMAGINI E RADIOTERAPIA ,030304 developmental biology ,Clinical Trials as Topic ,0303 health sciences ,Rectal Neoplasms ,Surrogate endpoint ,business.industry ,TOTAL MESORECTAL EXCISION ,Outcome measures ,RANDOMIZED PHASE-III ,medicine.disease ,Treatment Outcome ,Oncology ,Research Design ,030220 oncology & carcinogenesis ,FOLLOW-UP ,business ,SURROGATE END-POINTS ,POSTOPERATIVE CHEMORADIOTHERAPY - Abstract
There is a large variability regarding the definition and choice of primary endpoints in phase 2 and phase 3 multimodal rectal cancer trials, resulting in inconsistency and difficulty of data interpretation. Also, surrogate properties of early and intermediate endpoints have not been systematically assessed. We provide a comprehensive review of clinical and surrogate endpoints used in trials for non-metastatic rectal cancer. The applicability, advantages, and disadvantages of these endpoints are summarised, with recommendations on clinical endpoints for the different phase trials, including limited surgery or non-operative management for organ preservation. We discuss how early and intermediate endpoints, including patient-reported outcomes and involvement of patients in decision making, can be used to guide trial design and facilitate consistency in reporting trial results in rectal cancer.
- Published
- 2020
11. Targeted therapy in acute myeloid leukemia
- Author
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Eveline S. J. M. de Bont, Steven M. Kornblau, and Anneke D. van Dijk
- Subjects
Proteomics ,RPPA ,EXPRESSION ,Proteome ,medicine.medical_treatment ,Cell ,PROTEIN ,Antineoplastic Agents ,Computational biology ,Biochemistry ,Mass Spectrometry ,RECOMMENDATIONS ,Targeted therapy ,Translational Research, Biomedical ,AML ,hemic and lymphatic diseases ,medicine ,Animals ,Humans ,Molecular Targeted Therapy ,acute leukemia ,reverse-phase protein arrays ,Molecular Biology ,Acute leukemia ,Proteomic Profile ,business.industry ,MUTATIONS ,Myeloid leukemia ,MASS-SPECTROMETRY ,RANDOMIZED PHASE-III ,CHEMOTHERAPY ,targeted therapy ,GEMTUZUMAB OZOGAMICIN ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,ADVERSE PROGNOSTIC-FACTOR ,Identification (biology) ,Personalized medicine ,business - Abstract
Introduction: The biological heterogeneity of acute myeloid leukemia (AML) complicates personalized medicine. Individual prognosis is typically based on the presence of chromosomal and genetic lesions. Nevertheless, these classifications often lack a priori information about response to therapy. Since the protein expression landscape reflects the functional activity state of cells, we hypothesize that analyzing this can be used for the identification of protein activity markers to provide better risk stratification as well as may provide targeted therapeutic guidance in AML. Areas covered: Herein, we review recently new adopted drugs in the treatment for AML and discuss how quantitative proteomic techniques may contribute to better therapeutic selection in AML. Expert commentary: The net functional state of the cell is defined by the activity of protein within all the pathways that are active in the cell. Recognition of the proteomic profile of the leukemic blast could, therefore, complement current classification systems by providing a better a priori description of what pathways are important within a cell as a guide to the selection of therapy for the patient.
- Published
- 2020
12. Targeted therapy in acute myeloid leukemia
- Subjects
Proteomics ,RPPA ,EXPRESSION ,MUTATIONS ,PROTEIN ,MASS-SPECTROMETRY ,RANDOMIZED PHASE-III ,CHEMOTHERAPY ,targeted therapy ,GEMTUZUMAB OZOGAMICIN ,RECOMMENDATIONS ,AML ,ADVERSE PROGNOSTIC-FACTOR ,acute leukemia ,reverse-phase protein arrays - Abstract
Introduction: The biological heterogeneity of acute myeloid leukemia (AML) complicates personalized medicine. Individual prognosis is typically based on the presence of chromosomal and genetic lesions. Nevertheless, these classifications often lack a priori information about response to therapy. Since the protein expression landscape reflects the functional activity state of cells, we hypothesize that analyzing this can be used for the identification of protein activity markers to provide better risk stratification as well as may provide targeted therapeutic guidance in AML. Areas covered: Herein, we review recently new adopted drugs in the treatment for AML and discuss how quantitative proteomic techniques may contribute to better therapeutic selection in AML. Expert commentary: The net functional state of the cell is defined by the activity of protein within all the pathways that are active in the cell. Recognition of the proteomic profile of the leukemic blast could, therefore, complement current classification systems by providing a better a priori description of what pathways are important within a cell as a guide to the selection of therapy for the patient.
- Published
- 2020
13. Treatment of Focal-Onset Seizures in Children: Should This Be More Etiology-Driven?
- Author
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Alec Aeby, Berten Ceulemans, and Lieven Lagae
- Subjects
Science & Technology ,etiology ,Clinical Neurology ,Neurosciences ,focal-onset seizure ,ADD-ON THERAPY ,RANDOMIZED PHASE-III ,MIGRATING PARTIAL SEIZURES ,syndrome ,PLACEBO-CONTROLLED TRIAL ,Neurology ,children ,NEWLY-DIAGNOSED EPILEPSY ,ANTIEPILEPTIC DRUG EFFICACY ,epilepsy ,antiseizure medication ,Human medicine ,Neurology (clinical) ,Neurosciences & Neurology ,TUBEROUS SCLEROSIS COMPLEX ,CENTROTEMPORAL SPIKES BECTS ,OFF-LABEL USE ,Life Sciences & Biomedicine ,CONTROLLED-RELEASE CARBAMAZEPINE - Abstract
To accelerate the process of licensing antiseizure medication (ASM) in children, extrapolation of efficacy data for focal-onset seizures from adults to children ≥2 or ≥4 years of age is now accepted. We summarized the efficacy evidence from randomized, controlled trials that was used to grant approval for the pediatric indication of focal-onset seizures for the different ASMs available in Europe. Data from high-quality randomized, controlled trials in young children are limited, especially on the use of ASMs in monotherapy. Licensure trials are typically focused on seizure type irrespective of etiology or epilepsy syndrome. We elaborate on the importance of etiology- or syndrome-driven research and treatment, illustrating this with examples of childhood epilepsy syndromes characterized by predominantly focal-onset seizures. Some of these syndromes respond well to standard ASMs used for focal-onset seizures, but others would benefit from a more etiology- or syndrome-driven approach. Advances in molecular genetics and neuroimaging have made it possible to reveal the underlying cause of a child's epilepsy and tailor research and treatment. More high-quality randomized, controlled trials based on etiology or syndrome type are needed, including those assessing effects on cognition and behavior. In addition, study designs such as "N-of-1 trials" could elucidate possible new treatment options in rare epilepsies. Broadening incentives currently in place to stimulate the development and marketing of drugs for rare diseases (applicable to some epilepsy syndromes) to more common pediatric epilepsy types and syndromes might be a means to enable high-quality trials, and ultimately allow more evidence-based treatment in children. ispartof: FRONTIERS IN NEUROLOGY vol:13 ispartof: location:Switzerland status: published
- Published
- 2021
14. Improved response rate in patients with prognostically poor locally advanced rectal cancer after treatment with induction chemotherapy and chemoradiotherapy when compared with chemoradiotherapy alone: A matched case-control study
- Author
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Voogt, E. L. K. and Voogt, E. L. K.
- Abstract
Introduction: The addition of induction chemotherapy (ICT) to neoadjuvant chemoradiotherapy (CRT) has the potential to improve outcomes in patients with locally advanced rectal cancer (LARC). However, patient selection is essential to prevent overtreatment. This study compared the complete response (CR) rate after treatment with and without ICT of LARC patients with prognostically poor characteristics. Methods: All LARC patients who were treated with neoadjuvant CRT, whether or not preceded by ICT, and who underwent surgery or were considered for a wait-and-see strategy between January 2016 and March 2020 in the Catharina Hospital Eindhoven, were retrospectively selected. LARC was defined as any T4 tumour, or a T2/T3 tumour with extramural venous invasion and/or tumour deposits and/or N2 lymph node status, and/or mesorectal fascia involvement (T3 tumours only). Case-control matching was per -formed based on the aforementioned characteristics. Results: Of 242 patients, 178 (74%) received CRT (CRT-group) and 64 patients (26%) received ICT followed by CRT (ICT-group). In the ICT-group, 3 patients (5%) did not receive the minimum of three cycles. In addition, in this selected cohort, compliance with radiotherapy was 100% in the ICT-group and 97% in the CRT-group. The CR rate was 30% in the ICT-group and 15% in the CRT-group (p = 0.011). After case-control matching, the CR rate was 28% and 9%, respectively (p = 0.013). Conclusion: Treatment including ICT seemed well tolerated and resulted in a high CR rate. Hence, this treatment strategy may facilitate organ preservation and improve survival in LARC patients with prog-nostically poor characteristics. (c) 2021 Elsevier Ltd, BASO -The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.
- Published
- 2021
15. Is Molecular Tailored-Therapy Changing the Paradigm for CNS Metastases in Breast Cancer?
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Raffaele Lodi, Monica Di Battista, S. Minichillo, Vincenzo Di Nunno, Enrico Franceschi, Lidia Gatto, Ilaria Maggio, Antonella Mura, Alicia Tosoni, Alba A. Brandes, Stefania Bartolini, and Vincenzo Di Nunno , Enrico Franceschi , Alicia Tosoni , Antonella Mura , Santino Minichillo , Monica Di Battista , Lidia Gatto , Ilaria Maggio , Raffaele Lodi , Stefania Bartolini , Alba Ariela Brandes
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Oncology ,medicine.medical_specialty ,TRASTUZUMAB EMTANSINE T-DM1 ,LEPTOMENINGEAL METASTASIS ,Pyridines ,Receptor, ErbB-2 ,LAPATINIB PLUS CAPECITABINE ,Central nervous system ,PROLONGED SURVIVAL ,Breast Neoplasms ,Disease ,Breast cancer ,Pharmacotherapy ,Trastuzumab ,Internal medicine ,medicine ,Humans ,GRADED PROGNOSTIC ASSESSMENT ,Pharmacology (medical) ,Oxazoles ,PI3K/AKT/mTOR pathway ,POSTOPERATIVE STEREOTACTIC RADIOSURGERY ,NERVOUS-SYSTEM METASTASES ,Taxane ,business.industry ,General Medicine ,RANDOMIZED PHASE-III ,medicine.disease ,SOLID TUMORS ,medicine.anatomical_structure ,MULTIPLE BRAIN METASTASES ,Neratinib ,Quinazolines ,Female ,business ,medicine.drug - Abstract
Breast cancer (BC) is the second most common tumour spreading to the central nervous system (CNS). The prognosis of patients with CNS metastases depends on several parameters including the molecular assessment of the disease. Although loco-regional treatment remains the best approach, systemic therapies are acquiring a role leading to remarkable long-lasting responses. The efficacy of these compounds diverges between tumours with different molecular assessments. Promising agents under investigation are drugs targeting the HER2 pathways such as tucatinib, neratinib, pyrotinib, trastuzumab deruxtecan. In addition, there are several promising agents under investigation for patients with triple-negative brain metastases (third-generation taxane, etirinotecan, sacituzumab, immune-checkpoint inhibitors) and hormone receptor-positive brain metastases (CDK 4/5, phosphoinositide-3-kinase-mammalian target of rapamycin [PI3K/mTOR] inhibitors). Also, the systemic treatment of leptomeningeal metastases, which represents a very negative prognostic site of metastases, is likely to change as several compounds are under investigation, some with interesting preliminary results. Here we performed a comprehensive review focusing on the current management of CNS metastases according to molecular subtypes, site of metastases (leptomeningeal vs brain), and systemic treatments under investigation.
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- 2021
16. Impact of geography on prognostic outcomes of 21,509 patients with metastatic colorectal cancer enrolled in clinical trials: an ARCAD database analysis
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Richard M. Goldberg, Leonard B. Saltz, Jean-Yves Doulliard, Aimery de Gramont, Eric Van Cutsem, Christophe Tournigard, Fairooz F. Kabbinavar, John Souglakos, Romain Cohen, Richard Adams, J. Randolph Hecht, John Zalcberg, Eduard Diaz Rubio, Hans-Joachim Schmoll, Matthew T. Seymour, Charles S. Fuchs, Shaheenah Dawood, Volker Heinemann, Paulo M. Hoff, Alan P. Venook, Takayuki Yoshino, Chiara Cremolini, Carsten Bokemeyer, Miriam Koopman, Tim Maughan, Jun Yin, Axel Grothey, Jeffrey P. Meyers, Herbert Hurwitz, Niall C. Tebbutt, Cornelis J. A. Punt, Benoist Chibaudel, Qian Shi, Oncology, and CCA - Cancer Treatment and Quality of Life
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medicine.medical_specialty ,cancer survival ,colorectal cancer ,country ,healthcare system ,meta-analysis ,randomized trial ,Colorectal cancer ,Population ,BEVACIZUMAB ,COMBINATION CHEMOTHERAPY ,CAPECITABINE ,law.invention ,LEUCOVORIN ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,medicine ,030212 general & internal medicine ,FINAL REPORT ,education ,RC254-282 ,Uncategorized ,Original Research ,education.field_of_study ,Science & Technology ,Performance status ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Cancer survival ,PLUS OXALIPLATIN ,RANDOMIZED PHASE-III ,medicine.disease ,FLUOROURACIL ,Clinical trial ,1ST-LINE TREATMENT ,Oncology ,030220 oncology & carcinogenesis ,Meta-analysis ,SURVIVAL ,business ,Life Sciences & Biomedicine ,Healthcare system - Abstract
Impact of geography on prognostic outcomes of 21,509 patients with metastatic colorectal cancer enrolled in clinical trials: an ARCAD database analysis\ud Show less\ud Jun Yin*, Shaheenah Dawood*, Romain Cohen, Jeff Meyers, John Zalcberg, Takayuki Yoshino, Matthew Seymour, Tim Maughan, Leonard Saltz, Eric Van Cutsem, Alan Venook, Hans-Joachim Schmoll, Richard Goldberg, Paulo Hoff, J. Randolph Hecht, Herbert Hurwitz, Cornelis Punt, Eduard Diaz Rubio, Miriam Koopman, Chiara Cremolini, Volker Heinemann, Christophe Tournigard, Carsten Bokemeyer, Charles Fuchs, Niall Tebbutt, John Souglakos, Jean-Yves Doulliard, Fairooz Kabbinavar, Benoist Chibaudel, Aimery de Gramont, Qian Shi, Axel Grothey, Richard AdamsFirst Published June 30, 2021 Research Article\ud https://doi.org/10.1177/17588359211020547\ud Article information \ud Article has an altmetric score of 7 Open AccessCreative Commons Attribution, Non Commercial 4.0 License\ud Article Information\ud Volume: 13\ud Article first published online: June 30, 2021; Issue published: January 1, 2021\ud Received: December 29, 2020; Accepted: May 05, 2021\ud Jun Yin*\ud Department of Health Sciences Research, Mayo Clinic, 200 First Street, SW Rochester, MN 55905, USA\ud Shaheenah Dawood*\ud Mediclinic City Hospital: North Wing, Dubai Health Care City, Dubai UAE\ud Romain Cohen\ud Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA\ud Jeff Meyers\ud Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA\ud John Zalcberg\ud School of Public Health and Preventative Medicine, Monash University, Melbourne, Australia\ud Takayuki Yoshino\ud Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan\ud Matthew Seymour\ud NIHR Clinical Research Network, Leeds, UK\ud Tim Maughan\ud CRUK/MRC Oxford Institute for Radiation Oncology, Oxford, UK\ud Leonard Saltz\ud Memory Sloan Kettering Cancer Center, New York, NY, USA\ud Eric Van Cutsem\ud Digestive Oncology, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium\ud Alan Venook\ud Department of Medicine, The University of California San Francisco, San Francisco, CA, USA\ud Hans-Joachim Schmoll\ud Klinik fur Innere Med IV, University Clinic Halle, Saale, Germany\ud Richard Goldberg\ud Department of Oncology, West Virginia University, Morgantown, WV, USA\ud Paulo Hoff\ud Centro de Oncologia de Brasilia do Sirio Libanes: Unidade Lago Sul, Siro Libanes, Brazil\ud J. Randolph Hecht\ud Ronald Reagan UCLA Medical Center, UCLS Medical Center, Santa Monica, CA, USA\ud Herbert Hurwitz\ud Duke Cancer Institute, Duke University, Durham, NC, USA\ud Cornelis Punt\ud Department of Medical Oncology, University of Amsterdam, Amsterdam, The Netherlands\ud Eduard Diaz Rubio\ud Department Oncology, Hospital Clínico San Carlos, Madrid, Spain\ud Miriam Koopman\ud Department of Medical Oncology, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands\ud Chiara Cremolini\ud Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy\ud Volker Heinemann\ud Department of Medical Oncology and Comprehensive Cancer Center, University of Munich, Munich, Germany\ud Christophe Tournigard\ud Hopital Henri Mondor, Creteil, France\ud Carsten Bokemeyer\ud Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany\ud Charles Fuchs\ud Director of Yale Cancer Center, Boston, MA, USA\ud Niall Tebbutt\ud Sydney Medical School, University of Sydney, Sydney, Australia\ud John Souglakos\ud University of Crete, Heraklion, Greece\ud Jean-Yves Doulliard\ud University of Nantes Medical School, Nantes, France\ud Fairooz Kabbinavar\ud UCLA Medical Center, Santa Monica, CA, USA\ud Benoist Chibaudel\ud Department of Medical Oncology, Franco-British Institute, Levallois-Perret, France\ud Aimery de Gramont\ud Department of Medical Oncology, Franco-British Institute, Levallois-Perret, France\ud Qian Shi\ud Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA\ud Axel Grothey\ud West Cancer Center, Germantown, TN, USA\ud Richard Adams\ud Cardiff University and Velindre Cancer Center, Cardiff, UK\ud \ud Corresponding Author:\ud \ud yin.jun@mayo.edu\ud *Co-first authors.\ud \ud https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).\ud Abstract\ud Background:\ud Benchmarking international cancer survival differences is necessary to evaluate and improve healthcare systems. Our aim was to assess the potential regional differences in outcomes among patients with metastatic colorectal cancer (mCRC) participating in international randomized clinical trials (RCTs).\ud \ud Design:\ud Countries were grouped into 11 regions according to the World Health Organization and the EUROCARE model. Meta-analyses based on individual patient data were used to synthesize data across studies and regions and to conduct comparisons for outcomes in a two-stage random-effects model after adjusting for age, sex, performance status, and time period. We used mCRC patients enrolled in the first-line RCTs from the ARCAD database, which provided enrolling country information. There were 21,509 patients in 27 RCTs included across the 11 regions.\ud \ud Results:\ud Main outcomes were overall survival (OS) and progression-free survival (PFS). Compared with other regions, patients from the United Kingdom (UK) and Ireland were proportionaly over-represented, older, with higher performance status, more frequently male, and more commonly not treated with biological therapies. Cohorts from central Europe and the United States (USA) had significantly longer OS compared with those from UK and Ireland (p = 0.0034 and p
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- 2021
17. Breast-Gynaecological & Immuno-Oncology International Cancer Conference (BGICC) Consensus and Recommendations for the Management of Triple-Negative Breast Cancer
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Jessica W.T. Leung, Sana Al-Sukhun, Omalkhair Abulkhair, Benjamin O. Anderson, Meteb Foheidi, Nagi S. El Saghir, Hany Abdel Aziz, Joseph Gligorov, Mohamed Sabry, Hamdy A. Azim, Hagar Elghazawy, Edith A. Perez, Frédérique Penault-Llorca, Bahadir M. Gulluoglu, Joaira Bakkach, Khaled Abdel Karim, Banu Arun, Pierfranco Conte, Valentina Guarneri, Hope S. Rugo, Hesham Elghazaly, Mohamed A Shehata, Mona Frolova, Philip Poortmans, Cheng Har Yip, Sandra M. Swain, Manal Mohamed El-mahdy, Nermean Bahie Eldin, Alaa Kandil, Mohamed El-Shinawi, Charles M. Balch, Marwan Ghosn, Wentao Yang, Matti Aapro, Heba M. El-Zawahry, Adel T. Aref, Armando E. Giuliano, Roberto Orecchia, Ruslan M. Paltuev, Ain Shams University (ASU), Department of Medicine, University of California San Francisco Comprehensive Cancer Center, San Francisco, CA 94158, Clinical Oncology Department, Kasr Alainy School of Medicine, Cairo University, Giza 12613, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, MedStar Health, Washington, DC 20007, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, Breast Center, Clinique de Genolier, 1272 Genolier, Department of Hematology & Oncology, Mayo Clinic, Jacksonville, FL 32224, University of Washington [Seattle], Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Department of Surgery, Oncology and Gastroenterology, University of Padova, Istituto Oncologico Veneto IOV IRCCS, 35128 Padova, Department of Internal Medicine, Division of Hematology Oncology, American University of Beirut Medical Center, Beirut 1107 2020, Subang Jaya Medical Centre, Kuala Lumpur 47500, Université Saint-Joseph de Beyrouth (USJ), University of Antwerp (UA), Clinical oncology Department, Menoufia University, Shebin Elkom 51132, Department of Surgery, Surgical Oncology Division, Cedars-Sinai Medical Center, Los Angeles, CA 90048, Department of Breast Imaging, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Breast & Endocrine Surgery Unit, Marmara University School of Medicine, University Hospital, Istanbul 34722, Federal State Budgetary Institution 'NN Blokhin National Medical Research Center of Oncology' of the Ministry of Health of the Russian Federation, 127994 Moscow, Surgical Oncology Department, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, Università degli Studi di Milano = University of Milan (UNIMI), Al Hyatt Oncology Practice, Amman 11183, Department of Clinical Oncology, Alexandria School of Medicine, Alexandria 21131, Russian Association of Oncological Mammology, Department of Breast Tumours of Federal State Budgetary Institution 'Petrov Research Institute of Oncology', 197758 Saint Petersburg, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Adult Medical Oncology, Princess Noorah Oncology Center, King Abdulaziz Medical City, Ministry of National Guard Health Affairs-Western Region, Jeddah 22384, Vice President of Galala University, Galala University, Suez 435611, Oncology Department, Alfaisal university, Alhabib Hospital, Riyad 11533, Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, University of Adelaide, Biomedical Genomics & Oncogenetics Research Laboratory, Faculty of Sciences and Techniques of Tangier, Abdel Malek Essaadi University, Tangier 90000, Elghazaly, Hesham, Rugo, Hope S., Azim, Hamdy A., Swain, Sandra M., Arun, Banu, Aapro, Matti, Perez, Edith A., Anderson, Benjamin O., Penault-Llorca, Frederique, Conte, Pierfranco, El Saghir, Nagi S., Yip, Cheng-Har, Ghosn, Marwan, Poortmans, Philip, Shehata, Mohamed A., Giuliano, Armando E., Leung, Jessica W. T., Guarneri, Valentina, Gligorov, Joseph, Gulluoglu, Bahadir M., Abdel Aziz, Hany, Frolova, Mona, Sabry, Mohamed, Balch, Charles M., Orecchia, Roberto, El-Zawahry, Heba M., Al-Sukhun, Sana, Abdel Karim, Khaled, Kandil, Alaa, Paltuev, Ruslan M., Foheidi, Meteb, El-Shinawi, Mohamed, ElMahdy, Manal, Abulkhair, Omalkhair, Yang, Wentao, Aref, Adel T., Bakkach, Joaira, Bahie Eldin, Nermean, Elghazawy, Hagar, Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo 11566, Breast Health Global Initiative, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA 98195, Hematology and Oncology Department, Saint Joseph University, Beirut 1104 2020, Iridium Kankernetwerk and Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Wilrijk-Antwer, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Scientific Directorate, IRCCS European Institute of Oncology (IEO), and University of Milan, 20122 Milan, Department of General Surgery, Faculty of Medicine, Ain Shams University, Cairo 11566, Department of Pathology, Ain shams University, Cairo 11566, and The School of Public Health, University of Adelaide, Adelaide 5005
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0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,POSTMASTECTOMY RADIOTHERAPY ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,education ,COMPLETE RESPONSE PCR ,Disease ,MUTATION CARRIERS ,Guidelines ,03 medical and health sciences ,NEOADJUVANT CHEMOTHERAPY ,0302 clinical medicine ,Breast cancer ,ADJUVANT CHEMOTHERAPY ,medicine ,DISEASE-FREE SURVIVAL ,TUMOR-INFILTRATING LYMPHOCYTES ,platinum ,LOCOREGIONAL RECURRENCE ,AMERICAN SOCIETY ,Triple-negative breast cancer ,RC254-282 ,business.industry ,BRCA mutations ,Consensus ,Immunotherapy ,Platinum ,Cancer conference ,Consensus conference ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Evidence-based medicine ,RANDOMIZED PHASE-III ,medicine.disease ,3. Good health ,Clinical trial ,030104 developmental biology ,Oncology ,consensus ,030220 oncology & carcinogenesis ,Family medicine ,triple-negative breast cancer ,Human medicine ,immunotherapy ,business ,Mastectomy - Abstract
Simple Summary Despite the impressive progress in the treatment of triple-negative breast cancer (TNBC), oncologists still face several provocative clinical scenarios in daily practice where clear evidence-based recommendations are lacking, and expert opinion is of utmost importance. In an attempt to seek guidance for these controversial topics in TNBC management, a consensus recommendations session for TNBC was held during the 12th round of the Breast-Gynaecological & Immuno-oncology International Cancer Conference (BGICC) Egypt, 2020. This special session convened a multidisciplinary committee of 35 panellists who specialize in breast cancer care from 13 countries. The consensus covered all the aspects of TNBC management starting from defining TNBC to the management of metastatic disease and highlighted the rapidly evolving landscape in this field. Consensus was reached in 70% of the statements (35/50). In addition, areas of warranted research were identified to guide future prospective clinical trials. Background: The management of patients with triple-negative breast cancer (TNBC) is challenging with several controversies and unmet needs. During the 12th Breast-Gynaecological & Immuno-oncology International Cancer Conference (BGICC) Egypt, 2020, a panel of 35 breast cancer experts from 13 countries voted on consensus guidelines for the clinical management of TNBC. The consensus was subsequently updated based on the most recent data evolved lately. Methods: A consensus conference approach adapted from the American Society of Clinical Oncology (ASCO) was utilized. The panellists voted anonymously on each question, and a consensus was achieved when >= 75% of voters selected an answer. The final consensus was later circulated to the panellists for critical revision of important intellectual content. Results and conclusion: These recommendations represent the available clinical evidence and expert opinion when evidence is scarce. The percentage of the consensus votes, levels of evidence and grades of recommendation are presented for each statement. The consensus covered all the aspects of TNBC management starting from defining TNBC to the management of metastatic disease and highlighted the rapidly evolving landscape in this field. Consensus was reached in 70% of the statements (35/50). In addition, areas of warranted research were identified to guide future prospective clinical trials.
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- 2021
18. Comparative Assessment of Clinical Benefit Using the ESMO-Magnitude of Clinical Benefit Scale Version 1.1 and the ASCO Value Framework Net Health Benefit Score
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Elisabeth G.E. de Vries, Dimitris Karlis, Mark R. Somerfield, Richard L. Schilsky, Jean-Yves Douillard, George Pentheroudakis, Martine Piccart, Jan Bogaerts, Panagiota Zygoura, Nicola Jane Latino, Urania Dafni, Dana S. Wollins, Elizabeth Garrett-Mayer, Nathan I. Cherny, Katerina Vervita, Christoph C. Zielinski, Josep Tabernero, Shannon E. McKernin, and Lowell E. Schnipper
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Comparative Effectiveness Research ,Cancer Research ,medicine.medical_specialty ,MEDICAL ONCOLOGY MAGNITUDE ,Time Factors ,Comparative effectiveness research ,MEDLINE ,Antineoplastic Agents ,Health benefits ,WILD-TYPE KRAS ,Double blind ,DOUBLE-BLIND ,03 medical and health sciences ,0302 clinical medicine ,Quality of life (healthcare) ,RENAL-CELL CARCINOMA ,Risk Factors ,Neoplasms ,Outcome Assessment, Health Care ,Health care ,Humans ,Medicine ,Medical physics ,030212 general & internal medicine ,AMERICAN SOCIETY ,Randomized Controlled Trials as Topic ,business.industry ,Reproducibility of Results ,RANDOMIZED PHASE-III ,Progression-Free Survival ,METASTATIC COLORECTAL-CANCER ,1ST-LINE TREATMENT ,Oncology ,030220 oncology & carcinogenesis ,Scale (social sciences) ,Quality of Life ,business ,SURROGATE END-POINTS ,Value framework - Abstract
PURPOSE To better understand the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1) and the ASCO Value Framework Net Health Benefit score version 2 (ASCO-NHB v2), ESMO and ASCO collaborated to evaluate the concordance between the frameworks when used to assess clinical benefit attributable to new therapies. METHODS The 102 randomized controlled trials in the noncurative setting already evaluated in the field testing of ESMO-MCBS v1.1 were scored using ASCO-NHB v2 by its developers. Measures of agreement between the frameworks were calculated and receiver operating characteristic curves used to define thresholds for the ASCO-NHB v2 corresponding to ESMO-MCBS v1.1 categories. Studies with discordant scoring were identified and evaluated to understand the reasons for discordance. RESULTS The correlation of the 102 pairs of scores for studies in the noncurative setting is estimated to be 0.68 (Spearman’s rank correlation coefficient; overall survival, 0.71; progression-free survival, 0.67). Receiver operating characteristic curves identified thresholds for ASCO-NHB v2 for facilitating comparisons with ESMO-MCBS v1.1 categories. After applying pragmatic threshold scores of 40 or less (ASCO-NHB v2) and 2 or less (ESMO-MCBS v1.1) for low benefit and 45 or greater (ASCO-NHB v2) and 4 to 5 (ESMO-MCBS v1.1) for substantial benefit, 37 discordant studies were identified. Major factors that contributed to discordance were different approaches to evaluation of relative and absolute gain for overall survival and progression-free survival, crediting tail of the curve gains, and assessing toxicity. CONCLUSION The agreement between the frameworks was higher than observed in other studies that sought to compare them. The factors that contributed to discordant scores suggest potential approaches to improve convergence between the scales.
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- 2019
19. Clinical benefit of systemic therapies for recurrent ovarian cancer-ESMO-MCBS scores
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An K.L. Reyners, M. van Kruchten, C. Sessa, Mathilde Jalving, H. van Tinteren, K.E. Broekman, Targeted Gynaecologic Oncology (TARGON), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
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Oncology ,EPITHELIAL OVARIAN ,Cancer Research ,medicine.medical_specialty ,MAINTENANCE THERAPY ,Bevacizumab ,medicine.medical_treatment ,Phases of clinical research ,ESMO-MCBS ,Disease ,Carcinoma, Ovarian Epithelial ,Medical Oncology ,chemotherapy ,Targeted therapy ,chemistry.chemical_compound ,DOUBLE-BLIND ,Internal medicine ,medicine ,Humans ,Original Research ,Ovarian Neoplasms ,Chemotherapy ,PLATINUM-BASED CHEMOTHERAPY ,business.industry ,PRIMARY PERITONEAL ,RIBOSE POLYMERASE INHIBITOR ,clinical benefit ,RANDOMIZED PHASE-III ,medicine.disease ,OPEN-LABEL ,targeted therapy ,PEGYLATED LIPOSOMAL DOXORUBICIN ,FALLOPIAN-TUBE ,ovarian cancer ,Paclitaxel ,chemistry ,Recurrent Ovarian Cancer ,Quality of Life ,Female ,Neoplasm Recurrence, Local ,Ovarian cancer ,business ,medicine.drug - Abstract
Background Licensed systemic treatment options for platinum-sensitive recurrent ovarian cancer are platinum-based chemotherapy and maintenance treatment with bevacizumab and poly (ADP-ribose) polymerase inhibitors. For platinum-resistant disease, several non-platinum options are available. We aimed to assess the clinical benefit of these treatments according to the European Society of Medical Oncology (ESMO)-Magnitude of Clinical Benefit Scale (MCBS). Materials and methods A PubMed search was carried out including all studies evaluating systemic treatment of recurrent epithelial ovarian cancer, from 1990 onwards. Randomised trials with an adequate comparator and design showing a statistically significant benefit of the study arm were independently scored by two blinded observers using the ESMO-MCBS. Results A total of 1127 papers were identified, out of which 61 reported results of randomised trials of sufficient quality. Nineteen trials showed statistically significant results and the studied treatments were graded according to ESMO-MCBS. Only three treatments showed substantial benefit (score of 4 on a scale of 1-5) according to the ESMO-MCBS: platinum-based chemotherapy with paclitaxel in the platinum-sensitive setting and the addition of bevacizumab to chemotherapy in the platinum-resistant setting. The WEE1 inhibitor adavosertib (not licensed) also scores a 4, based on a recent small phase II study. Assessment of quality-of-life data and toxicity using the ESMO-MCBS showed to be complex, which should be taken into account in using this score for clinical decision making. Conclusion Only a few licensed systemic therapies for recurrent ovarian cancer show substantial clinical benefit based on ESMO-MCBS scores. Trials demonstrating overall survival benefit are sparse., Highlights • Benefit of systemic treatments for recurrent ovarian cancer was scored on the ESMO-MCBS. • From 1127 identified papers, only 3 trials out of 19 that were suitable for grading showed substantial clinical benefit. • Trials demonstrating overall survival benefit are sparse.
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- 2021
20. The 2017 Assisi Think Tank Meeting on rectal cancer: A positioning paper
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Valentini, Vincenzo and Valentini, Vincenzo
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Background and purposes: To describe current practice in the management of rectal cancer, to identify uncertainties that usually arise in the multidisciplinary team (MDT)'s discussions ('grey zones') and propose next generation studies which may provide answers to them.Materials and methods: A questionnaire on the areas of controversy in managing T2, T3 and T4 rectal cancer was drawn up and distributed to the Rectal-Assisi Think Tank Meeting (ATTM) Expert European Board. Less than 70% agreement on a treatment option was indicated as uncertainty and selected as a 'grey zone'. Topics with large disagreement were selected by the task force group for discussion at the Rectal-ATTM.Results: The controversial clinical issues that had been identified within cT2-cT3-cT4 needed further investigation. The discussions focused on the role of (1) neoadjuvant therapy and organ preservation on cT2-3a low-middle rectal cancer; (2) neoadjuvant therapy in cT3 low rectal cancer without high risk features; (3) total neoadjuvant therapy, radiotherapy boost and the best chemo-radiotherapy schedule in T4 tumors. A description of each area of investigation and trial proposals are reported.Conclusion: The meeting successfully identified 'grey zones' and, in the light of new evidence, proposed clinical trials for treatment of early, intermediate and advanced stage rectal cancer. (C) 2019 Published by Elsevier B.V.
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- 2020
21. Outcome measures in multimodal rectal cancer trials
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Fokas, Emmanouil and Fokas, Emmanouil
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There is a large variability regarding the definition and choice of primary endpoints in phase 2 and phase 3 multimodal rectal cancer trials, resulting in inconsistency and difficulty of data interpretation. Also, surrogate properties of early and intermediate endpoints have not been systematically assessed. We provide a comprehensive review of clinical and surrogate endpoints used in trials for non-metastatic rectal cancer. The applicability, advantages, and disadvantages of these endpoints are summarised, with recommendations on clinical endpoints for the different phase trials, including limited surgery or non-operative management for organ preservation. We discuss how early and intermediate endpoints, including patient-reported outcomes and involvement of patients in decision making, can be used to guide trial design and facilitate consistency in reporting trial results in rectal cancer.
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- 2020
22. Management of glioblastoma: State of the art and future directions
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- 2020
23. Biliary tract cancers: molecular heterogeneity and new treatment options
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Tiziana Pressiani, Athanasios Pouptsis, Chara Stavraka, Nicola Personeni, Mark R. Openshaw, David J. Pinato, Francesca Colapietro, Lorenza Rimassa, and Ana Lleo
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0301 basic medicine ,Oncology ,IDH ,Cancer Research ,medicine.medical_specialty ,targeted agents ,medicine.medical_treatment ,ISOCITRATE DEHYDROGENASE 1 ,Review ,Disease ,lcsh:RC254-282 ,THERAPEUTIC TARGETS ,molecular characterization ,03 medical and health sciences ,DOUBLE-BLIND ,0302 clinical medicine ,Internal medicine ,biliary tract cancer ,tumor heterogeneity ,medicine ,TUMOR-SUPPRESSOR ,1112 Oncology and Carcinogenesis ,Epigenetics ,Intrahepatic Cholangiocarcinoma ,Chemotherapy ,Science & Technology ,Fibroblast growth factor receptor 2 ,business.industry ,FGFR ,RANDOMIZED PHASE-III ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,OPEN-LABEL ,PLUS S-1 ,030104 developmental biology ,BRAF GENE ,Biliary tract ,Fibroblast growth factor receptor ,030220 oncology & carcinogenesis ,INTRAHEPATIC CHOLANGIOCARCINOMAS ,business ,cholangiocarcinoma ,GROWTH-FACTOR RECEPTOR ,Adjuvant ,Life Sciences & Biomedicine - Abstract
Simple Summary Incidence of biliary tract cancer is increasing, and patients are frequently diagnosed with unresectable or metastatic disease, when therapeutic options are limited. Due to these reasons, prognosis remains poor and new systemic treatment options are urgently needed. This article reviews the new available data on molecular heterogeneity of biliary tract cancer and especially intrahepatic cholangiocarcinoma and the novel therapeutic strategies offered by the improved knowledge of the biology of this disease. For these reasons, this topic is of relevant interest for the oncology and hepatology community. Abstract Most patients with biliary tract cancer (BTC) are diagnosed with advanced disease, relapse rates are high in those undergoing surgery and prognosis remains poor, while the incidence is increasing. Treatment options are limited, and chemotherapy is still the standard of care in both adjuvant and advanced disease setting. In recent years, different subtypes of BTC have been defined depending on the anatomical location and genetic and/or epigenetic aberrations. Especially for intrahepatic cholangiocarcinoma (iCCA) novel therapeutic targets have been identified, including fibroblast growth factor receptor 2 gene fusions and isocitrate dehydrogenase 1 and 2 mutations, with molecularly targeted agents having shown evidence of activity in this subgroup of patients. Additionally, other pathways are being evaluated in both iCCA and other subtypes of BTC, alongside targeting of the immune microenvironment. The growing knowledge of BTC biology and molecular heterogeneity has paved the way for the development of new therapeutic approaches that will completely change the treatment paradigm for this disease in the near future. This review provides an overview of the molecular heterogeneity of BTC and summarizes new targets and emerging therapies in development. We also discuss resistance mechanisms, open issues, and future perspectives in the management of BTC.
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- 2020
24. Observed versus modelled lifetime overall survival of targeted therapies and immunotherapies for advanced non-small cell lung cancer patients - A systematic review
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Valesca P. Retèl, Marthe S. Paats, Wim H. van Harten, Joanne Mankor, Joachim G.J.V. Aerts, Manuela A. Joore, Martijn Simons, Andrea Peeters, Bram Ramaekers, and Pulmonary Medicine
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,Cost-Benefit Analysis ,medicine.medical_treatment ,ERLOTINIB ,03 medical and health sciences ,0302 clinical medicine ,Targeted therapies ,Non-small cell lung cancer ,SDG 3 - Good Health and Well-being ,CARBOPLATIN-PACLITAXEL ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Overall survival ,Humans ,Medicine ,Lung cancer ,Survival analysis ,DOCETAXEL ,business.industry ,Cancer ,ADENOCARCINOMA ,Hematology ,Immunotherapy ,Stage iiib ,RANDOMIZED PHASE-III ,CHEMOTHERAPY ,medicine.disease ,OPEN-LABEL ,n/a OA procedure ,1ST-LINE TREATMENT ,030104 developmental biology ,030220 oncology & carcinogenesis ,TRIAL ,Non small cell ,business ,Immunotherapies ,COMPARING GEFITINIB - Abstract
Outcomes used for the effectiveness (median) and cost-effectiveness (mean) on overall survival (OS) are different and can vary from one another. Therefore, we compared median and mean OS gains of targeted therapies and immunotherapies for stage IIIB/IV Non-small cell lung cancer and explored underlying aspect. Eligible trials were searched in PubMed, survival curves were digitized, and parametric survival models fitted to model the mean OS. Twenty-seven trials were found for targeted therapies (n = 17) and immunotherapies (n = 10). Differences between median and mean OS gains in months ranged from -2.8 to 6.8 and -4.9 to 0.3 for two different subgroups of targeted therapies, and -2.4 to 11.4 for immunotherapies. The mean OS gain was substantially larger for most immunotherapy trials, due to relatively long survival. Median and mean OS gains did not differ for targeted therapies. Our findings imply a potential discrepancy between the estimates of effectiveness and cost-effectiveness of cancer treatments.
- Published
- 2020
25. Observed versus modelled lifetime overall survival of targeted therapies and immunotherapies for advanced non-small cell lung cancer patients - A systematic review
- Subjects
DOCETAXEL ,ERLOTINIB ,ADENOCARCINOMA ,Survival analysis ,RANDOMIZED PHASE-III ,CHEMOTHERAPY ,OPEN-LABEL ,1ST-LINE TREATMENT ,Targeted therapies ,Non-small cell lung cancer ,CARBOPLATIN-PACLITAXEL ,Overall survival ,TRIAL ,Immunotherapies ,COMPARING GEFITINIB - Abstract
Outcomes used for the effectiveness (median) and cost-effectiveness (mean) on overall survival (OS) are different and can vary from one another. Therefore, we compared median and mean OS gains of targeted therapies and immunotherapies for stage IIIB/IV Non-small cell lung cancer and explored underlying aspect. Eligible trials were searched in PubMed, survival curves were digitized, and parametric survival models fitted to model the mean OS. Twenty-seven trials were found for targeted therapies (n = 17) and immunotherapies (n = 10). Differences between median and mean OS gains in months ranged from - 2.8 to 6.8 and - 4.9 to 0.3 for two different subgroups of targeted therapies, and -2.4 to 11.4 for immunotherapies. The mean OS gain was substantially larger for most immunotherapy trials, due to relatively long survival. Median and mean OS gains did not differ for targeted therapies. Our findings imply a potential discrepancy between the estimates of effectiveness and cost-effectiveness of cancer treatments.
- Published
- 2020
26. Monosomal karyotype and chromosome 17p loss or TP53 mutations in decitabine-treated patients with acute myeloid leukemia
- Author
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Lars Bullinger, Milena Pantic, Arnold Ganser, Pierre W. Wijermans, Björn Rüter, Anne Hagemeijer, Björn Hackanson, Dietmar Pfeifer, Hartmut Döhner, Gabriele Ihorst, Konstanze Döhner, Uwe Platzbecker, Michael Lübbert, Julius Wehrle, Andrea Kuendgen, Ulrich Germing, Justus Duyster, and Heiko Becker
- Subjects
Oncology ,Male ,Cancer Research ,IMPACT ,DNA Mutational Analysis ,Gene mutation ,medicine.disease_cause ,Monosomy ,AML ,Germany ,TP53 ,DNA METHYLATION ,Aged, 80 and over ,Mutation ,Hematology ,SUBGROUP ANALYSIS ,Myeloid leukemia ,General Medicine ,Middle Aged ,COOPERATIVE GROUP ,Leukemia, Myeloid, Acute ,HYPOMETHYLATING AGENTS ,Cohort ,SURVIVAL ,Original Article ,Female ,Chromosome Deletion ,Life Sciences & Biomedicine ,Mutations ,medicine.drug ,medicine.medical_specialty ,Karyotype ,Decitabine ,Clonal Evolution ,Internal medicine ,SUPPORTIVE CARE ,medicine ,MYELODYSPLASTIC SYNDROMES ,Humans ,ddc:610 ,neoplasms ,Aged ,Science & Technology ,Acute myeloid leukemia ,OLDER PATIENTS ,business.industry ,Cytogenetics ,RANDOMIZED PHASE-III ,medicine.disease ,Survival Analysis ,Karyotyping ,Smith-Magenis Syndrome ,Tumor Suppressor Protein p53 ,business ,Chromosomes, Human, Pair 17 - Abstract
TP53 aberrations reportedly predict favorable responses to decitabine (DAC) in acute myeloid leukemia (AML). We evaluated clinical features and outcomes associated with chromosome 17p loss or TP53 gene mutations in older, unfit DAC-treated AML patients in a phase II trial. Of 178 patients, 25 had loss of 17p in metaphase cytogenetics; 24 of these had a complex (CK+) and 21 a monosomal karyotype (MK+). In analyses in all patients and restricted to CK+ and MK+ patients, 17p loss tended to associate with higher rates of complete remission (CR), partial remission (PR), or antileukemic effect (ALE). Despite favorable response rates, there was no significant OS difference between patients with or without loss of 17p in the entire cohort or in the CK+ and MK+ cohort. TP53 mutations were identified in eight of 45 patients with material available. Five of the eight TP53-mutated patients had 17p loss. TP53-mutated patients had similar rates of CR/PR/ALE but shorter OS than those with TP53 wild type (P = 0.036). Moreover, patients with a subclone based on mutation data had shorter OS than those without (P = 0.05); only one patient with TP53-mutated AML had a subclone. In conclusion, 17p loss conferred a favorable impact on response rates, even among CK+ and MK+ patients that however could not be maintained. The effect of TP53 mutations appeared to be different; however, patient numbers were low. Future research needs to further dissect the impact of the various TP53 aberrations in HMA-based combination therapies. The limited duration of favorable responses to HMA treatment in adverse-risk genetics AML should prompt physicians to advance allografting for eligible patients in a timely fashion.
- Published
- 2020
27. The 2017 Assisi Think Tank Meeting on rectal cancer: A positioning paper
- Author
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Cynthia Aristei, Andrés Cervantes, Harm J. T. Rutten, Giuditta Chiloiro, Corrie A.M. Marijnen, Berardino De Bari, Cornelis J.H. van de Velde, Vincenzo Valentini, Claus Rödel, Rob Glynne-Jones, Geerard L. Beets, Karin Haustermans, Krzysztof Bujko, Maria Antonietta Gambacorta, E. Meldolesi, Femke P. Peters, Claudio Coco, Faculteit FHML Centraal, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, and Surgery
- Subjects
Male ,Best practice guidelines ,Colorectal cancer ,medicine.medical_treatment ,Settore MED/18 - CHIRURGIA GENERALE ,Medical Oncology ,030218 nuclear medicine & medical imaging ,COLORECTAL-CANCER ,0302 clinical medicine ,ADJUVANT CHEMOTHERAPY ,Rectal cancer ,Neoadjuvant therapy ,Randomized Controlled Trials as Topic ,Settore MED/36 - DIAGNOSTICA PER IMMAGINI E RADIOTERAPIA ,Radiology, Nuclear Medicine & Medical Imaging ,Chemoradiotherapy ,Cytoreduction Surgical Procedures ,Hematology ,Middle Aged ,OPEN-LABEL ,Total mesorectal excision ,Neoadjuvant Therapy ,Oncology ,030220 oncology & carcinogenesis ,Female ,Life Sciences & Biomedicine ,medicine.medical_specialty ,Organ preservation ,LOCAL RECURRENCE ,Areas of uncertainties ,COURSE PREOPERATIVE RADIOTHERAPY ,Personalized medicine ,03 medical and health sciences ,Low rectal cancer ,RADIATION-THERAPY ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Medical physics ,EXTRAMURAL VASCULAR INVASION ,Neoplasm Staging ,Science & Technology ,Rectal Neoplasms ,business.industry ,Task force ,TOTAL MESORECTAL EXCISION ,RANDOMIZED PHASE-III ,NEOADJUVANT CHEMORADIOTHERAPY ,medicine.disease ,Clinical trial ,Radiation therapy ,business - Abstract
BACKGROUND AND PURPOSES: To describe current practice in the management of rectal cancer, to identify uncertainties that usually arise in the multidisciplinary team (MDT)'s discussions ('grey zones') and propose next generation studies which may provide answers to them. MATERIALS AND METHODS: A questionnaire on the areas of controversy in managing T2, T3 and T4 rectal cancer was drawn up and distributed to the Rectal-Assisi Think Tank Meeting (ATTM) Expert European Board. Less than 70% agreement on a treatment option was indicated as uncertainty and selected as a 'grey zone'. Topics with large disagreement were selected by the task force group for discussion at the Rectal-ATTM. RESULTS: The controversial clinical issues that had been identified within cT2-cT3-cT4 needed further investigation. The discussions focused on the role of (1) neoadjuvant therapy and organ preservation on cT2-3a low-middle rectal cancer; (2) neoadjuvant therapy in cT3 low rectal cancer without high risk features; (3) total neoadjuvant therapy, radiotherapy boost and the best chemo-radiotherapy schedule in T4 tumors. A description of each area of investigation and trial proposals are reported. CONCLUSION: The meeting successfully identified 'grey zones' and, in the light of new evidence, proposed clinical trials for treatment of early, intermediate and advanced stage rectal cancer. ispartof: RADIOTHERAPY AND ONCOLOGY vol:142 pages:6-16 ispartof: location:ITALY, Assisi status: published
- Published
- 2020
28. Ramucirumab for Treating Advanced Gastric Cancer or Gastro-Oesophageal Junction Adenocarcinoma Previously Treated with Chemotherapy
- Subjects
HEALTH STATE UTILITIES ,IRINOTECAN ,PLUS ,SUPPORTIVE CARE ,MONOTHERAPY ,TRIAL ,RANDOMIZED PHASE-III ,PACLITAXEL ,OPEN-LABEL ,COMBINATION - Abstract
The National Institute for Health and Care Excellence (NICE) invited the company that manufactures ramucirumab (Cyramza(A (R)), Eli Lilly and Company) to submit evidence of the clinical and cost effectiveness of the drug administered alone (monotherapy) or with paclitaxel (combination therapy) for treating adults with advanced gastric cancer or gastro-oesophageal junction (GC/GOJ) adenocarcinoma that were previously treated with chemotherapy, as part of the Institute's single technology appraisal (STA) process. Kleijnen Systematic Reviews Ltd (KSR), in collaboration with Erasmus University Rotterdam, was commissioned to act as the Evidence Review Group (ERG). This paper describes the company's submission, the ERG review, and NICE's subsequent decisions. Clinical effectiveness evidence for ramucirumab monotherapy (RAM), compared with best supportive care (BSC), was based on data from the REGARD trial. Clinical effectiveness evidence for ramucirumab combination therapy (RAM + PAC), compared with paclitaxel monotherapy (PAC), was based on data from the RAINBOW trial. In addition, the company undertook a network meta-analysis (NMA) to compare RAM + PAC with BSC and docetaxel. Cost-effectiveness evidence of monotherapy and combination therapy relied on partitioned survival, cost-utility models. The base-case incremental cost-effectiveness ratio (ICER) of the company was A 188,640 pound (vs BSC) per quality-adjusted life-year (QALY) gained for monotherapy and A 118,209 pound (vs BSC) per QALY gained for combination therapy. The ERG assessment indicated that the modelling structure represented the course of the disease; however, a few errors were identified and some of the input parameters were challenged. The ERG provided a new base case, with ICERs (vs BSC) of A 188,100 pound (monotherapy) per QALY gained and A 129,400 pound (combination therapy) per QALY gained and conducted additional exploratory analyses. The NICE Appraisal Committee (AC), considered the company's decision problem was in line with the NICE scope, with the exception of the choice of comparators for the combination therapy model. The most plausible ICER for ramucirumab monotherapy compared with BSC was A 188,100 pound per QALY gained. The Committee considered that the ERG's exploratory analysis in which RAM + PAC was compared with PAC by using the direct head-to-head data (including utilities) from the RAINBOW trial, provided the most plausible ICER (i.e. A 408,200 pound per QALY gained) for ramucirumab combination therapy. The Committee concluded that end-of-life considerations cannot be applied for either case, since neither failed to offer an extension to life of at least 3 months. The company did not submit a patient access scheme (PAS). After consideration of the evidence, the Committee concluded that ramucirumab alone or with paclitaxel could not be considered a cost-effective use of National Health Service resources for treating advanced GC/GOJ patients that were previously treated with chemotherapy, and therefore its use could not be recommended. We might wonder if a complete STA process is necessary for treatments without a PAS, which are, according to the company's submission, already associated with ICERs far above the currently accepted threshold in all (base-case, sensitivity and scenario) analyses.
- Published
- 2017
29. Real-world and trial-based cost-effectiveness analysis of bevacizumab in HER2-negative metastatic breast cancer patients
- Author
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J.M.G.H. van Riel, M. de Boer, N.A.J.B. Peters, F.P.J. Peters, Vivianne C. G. Tjan-Heijnen, M.W. Dercksen, Tineke J. Smilde, F.W.P.J. van den Berkmortel, Dorien J.A. Lobbezoo, Bram Ramaekers, Manuela A. Joore, R.J.W. van Kampen, A.J. van de Wouw, RS: CAPHRI - R2 - Creating Value-Based Health Care, MUMC+: KIO Kemta (9), MUMC+: MA Med Staf Artsass Interne Geneeskunde (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Interne Geneeskunde, MUMC+: MA Medische Oncologie (9), MUMC+: TPZ Ergotherapie (9), and Health Services Research
- Subjects
Bridged-Ring Compounds ,Oncology ,Cancer Research ,medicine.medical_specialty ,Bevacizumab ,Receptor, ErbB-2 ,Trial based ,Breast Neoplasms ,Docetaxel ,Kaplan-Meier Estimate ,PACLITAXEL ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,PLUS DOCETAXEL ,Humans ,030212 general & internal medicine ,Netherlands ,Taxane ,Cost–benefit analysis ,business.industry ,Cost-effectiveness analysis ,HER2 negative ,Cost-benefit analysis ,WOMEN ,RANDOMIZED PHASE-III ,medicine.disease ,Metastatic breast cancer ,Surgery ,1ST-LINE TREATMENT ,Real-world ,030220 oncology & carcinogenesis ,Disease Progression ,Health Resources ,Female ,Taxoids ,Quality-Adjusted Life Years ,business ,medicine.drug ,Cohort study - Abstract
Introduction: The aim of our analysis was to assess the real-world cost-effectiveness of bevacizumab in addition to taxane treatment versus taxane monotherapy for HER2-negative metastatic breast cancer compared with the cost-effectiveness based on the efficacy results from a trial.Methods: A state transition model was built to estimate costs, life years (LYs) and quality-adjusted life years (QALYs) for both treatments. Two scenarios were examined: a real-world scenario and a trial-based scenario in which transition probabilities were primarily based on a real-world cohort study and the E2100 trial, respectively. In both scenarios, costs and utility parameter estimates were extracted from the real-world cohort study. Moreover, the Dutch health care perspective was adopted.Results: In both the real-world and trial scenarios, bevacizumab-taxane is more expensive (incremental costs of (sic)56,213 and (sic)52,750, respectively) and more effective (incremental QALYs of 0.362 and 0.189, respectively) than taxane monotherapy. In the real-world scenario, bevacizumab-taxane compared to taxane monotherapy led to an incremental cost-effectiveness ratio (ICER) of (sic)155,261 per QALY gained. In the trial scenario, the ICER amounted to (sic)278,711 per QALY gained.Conclusion: According to the Dutch informal threshold, bevacizumab in addition to taxane treatment was not considered cost-effective for HER2-negative metastatic breast cancer both in a real-world and in a trial scenario. (C) 2017 Elsevier Ltd. All rights reserved.
- Published
- 2017
30. Evaluation of perampanel in patients with intellectual disability and epilepsy
- Author
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In Y. Tan, Francesca M. Snoeijen-Schouwenaars, Jans S. van Ool, Helenius J. Schelhaas, Marian Majoie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, and RS: SHE - R1 - Research (OvO)
- Subjects
Male ,Drug Resistant Epilepsy ,Intellectual disability ,MULTICENTER ,Perampanel ,PARTIAL-ONSET SEIZURES ,Behavioral Neuroscience ,chemistry.chemical_compound ,Epilepsy ,0302 clinical medicine ,030212 general & internal medicine ,Young adult ,Child ,Middle Aged ,CLINICAL-EXPERIENCES ,Neurology ,Child, Preschool ,Anticonvulsants ,Female ,Adult ,medicine.medical_specialty ,Adolescent ,Efficacy ,Pyridones ,Young Adult ,03 medical and health sciences ,PEOPLE ,Internal medicine ,Nitriles ,medicine ,Humans ,Receptors, AMPA ,ADJUNCTIVE PERAMPANEL ,Psychiatry ,Adverse effect ,Aged ,Retrospective Studies ,Polypharmacy ,Behavior ,Adverse effects ,business.industry ,Retrospective cohort study ,RANDOMIZED PHASE-III ,medicine.disease ,Discontinuation ,chemistry ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Follow-Up Studies - Abstract
Introduction: Initial registration studies of perampanel (PMP), an AMPA receptor antagonist, have now been followed up by 'clinical' studies that confirmed its efficacy and safety in patients with refractory epilepsy. Publications on the use of PMP among patients with intellectual disability (ID) are still limited. This study extends our knowledge with respect to the relevance of PMP for patients with both ID and epilepsy, and furthermore specifies the behavioral side effects of PMP in this specific population.Methods: Retrospective evaluation of medical records at 3, 6 and 12 months of follow-up after the initial start of PMP.Results: 62 patients were included. 21 patients (33.9%) were female. All patients had complete data of 6 months follow-up and we were able to review 42 patients with a 1-year follow-up. Level of ID varied from borderline to profound, and mild ID was most common (43.5%). The mean maximum daily dosage of PMP was 5.6 mg (range 1-12 mg). Retention rates for PMP were 87.1% and 67.7% after three and six months. A trend indicated a longer mean retention time in patients with a more severe ID (borderline-mild-moderate ID: 205 days, severe-profound ID: 275 days). Seizure reduction was achieved in 53.2%. 36 patients (58.1%) experienced adverse effects, 80.6% of those within 3 months. 45.2% of the patients experienced somatic adverse effects. Most common were fatigue & sleep problems, motor problems & unsteadiness, and gastrointestinal problems. Behavioral adverse effects were present in 40.3%. Most common were aggression, agitated behavior, disruptive behavior, and mood symptoms. Reasons for discontinuation of PMP were lack of efficacy in 14.8%, intolerable adverse effects in 44.4%, and a combination of both in 40.7%.Altogether, 24.2% (15/62) of the patients achieved seizure reduction without experiencing adverse effects, though none reached seizure freedom.Conclusions: The use of PMP might lead to an effective seizure reduction without adverse effects in a minority of patients with both epilepsy and ID. Pre-existing behavioral problems or polypharmacy do not predict the occurrence of additional behavioral adverse effects, implying that these patients need not be excluded from the introduction of PMP when clinically indicated. Patients should, ideally, be monitored at a multidisciplinary clinic. (C) 2016 Elseyier Inc. All rights reserved.
- Published
- 2017
31. Interdisciplinary multimodality management of stage III nonsmall cell lung cancer
- Subjects
ACCELERATED RADIOTHERAPY ,LEUKEMIA-GROUP-B ,INDIVIDUAL PATIENT DATA ,INDUCTION CHEMOTHERAPY ,CONCURRENT CHEMORADIOTHERAPY ,PREOPERATIVE CHEMOTHERAPY ,THORACIC RADIOTHERAPY ,GROWTH-FACTOR-RECEPTOR ,RANDOMIZED PHASE-III ,HYPERFRACTIONATED RADIATION-THERAPY - Abstract
Stage III nonsmall cell lung cancer (NSCLC) comprises about one-third of NSCLC patients and is very heterogeneous with varying and mostly poor prognosis. It is also called "locoregionally or locally advanced disease". Due to its heterogeneity a general schematic management approach is not appropriate. Usually a combination of local therapy (surgery or radiotherapy, depending on functional, technical and oncological operability) with systemic platinum-based doublet chemotherapy and, recently, followed by immune therapy is used. A more aggressive approach of triple agent chemotherapy or two local therapies (surgery and radiotherapy, except for specific indications) has no benefit for overall survival. Until now tumour stage and the general condition of the patient are the most relevant prognostic factors. Characterising the tumour molecularly and immunologically may lead to a more personalised and effective approach. At the moment, after an exact staging and functional evaluation, an interdisciplinary discussion amongst the tumour board is warranted and offers the best management strategy.
- Published
- 2019
32. Quality of Life of Patients With Osteosarcoma in the European American Osteosarcoma Study-1 (EURAMOS-1): Development and Implementation of a Questionnaire Substudy
- Author
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Mark L. Bernstein, Andreas Wiener, Neyssa Marina, Jeremy Whelan, Katja Baust, Lars Hjorth, Gordana Jovic, Meriel Jenney, Patricia de Vos, Babasola O Popoola, Stefan S. Bielack, Mark Krailo, Gabriele Calaminus, Pancras C.W. Hogendoorn, Cristina Sauerland, Sigbjørn Smeland, Carmen Teske, Rajaram Nagarajan, Clara V Schweinitz, Matthew R. Sydes, and Kiana Kreitz
- Subjects
medicine.medical_specialty ,sarcoma ,Medizin ,Psychological intervention ,Disease ,INTERNATIONAL COLLABORATION ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Quality of life ,law ,osteosarcoma ,ADOLESCENTS ,medicine ,Medicine and Health Sciences ,HISTOLOGIC RESPONSE ,cancer ,Young adult ,GENERIC CORE SCALES ,030304 developmental biology ,0303 health sciences ,Original Paper ,child ,business.industry ,MURAMYL TRIPEPTIDE ,survivors of childhood cancer ,General Medicine ,RANDOMIZED PHASE-III ,CHEMOTHERAPY ,CANCER ,humanities ,3. Good health ,Group Affiliation ,quality of life ,030220 oncology & carcinogenesis ,adolescent ,Cohort ,Physical therapy ,SURVIVAL ,young adult ,Observational study ,observational study ,business ,HIGH-GRADE OSTEOSARCOMA - Abstract
Background The quality of life (QoL) of patients with osteosarcoma (OS) may be adversely affected by the disease or its treatment. Therefore, it is important to understand the QoL of patients undergoing treatment for OS to improve the QoL. We report on the first prospective international QoL study that was embedded within a large randomized clinical trial from 4 national study groups. Objective This paper aimed to describe the QoL study development, methodology, accrual details, and characteristics of the QoL cohort. Methods A total of 2260 patients registered in the EURopean AMerican Osteosarcoma Study-1 (EURAMOS-1), of whom 97.92% (2213/2260) were eligible for the optional QoL assessment and could participate in terms of questionnaire availability. Overall, 61.86% (1369/2213) of patients and/or proxies completed the QoL evaluation at the first assessment time point (E1) after the start of preoperative treatment. The QoL measures used (self- and/or proxy reports) depending on the patient’s age and national study group. Participants and nonparticipants in the ancillary QoL study were compared regarding relevant demographic and disease-related characteristics at registration in the trial. Results The participation rate at time point E1 did not differ with regard to age, gender, the occurrence of pathological fracture, or the presence of any metastases at diagnosis. No differences were found regarding the primary tumor site. Only the national study group affiliation had an influence on participation. Participation decreased linearly with trial progress up to 20% at the final time point of QoL assessment. Conclusions This study demonstrates the feasibility of international cooperation for the purpose of assessing and understanding the QoL of pediatric and adolescent/young adult patients with cancer. Future outcomes of this QoL substudy will help to adapt interventions to improve QoL.
- Published
- 2019
33. Interdisciplinary multimodality management of stage III nonsmall cell lung cancer
- Author
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Simone Reu, Dirk De Ruysscher, Rudolf M. Huber, Hans Hoffmann, and Amanda Tufman
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,ACCELERATED RADIOTHERAPY ,medicine.medical_treatment ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,INDUCTION CHEMOTHERAPY ,CONCURRENT CHEMORADIOTHERAPY ,medicine ,Carcinoma ,Humans ,THORACIC RADIOTHERAPY ,030212 general & internal medicine ,HYPERFRACTIONATED RADIATION-THERAPY ,Stage (cooking) ,Pneumonectomy ,Neoplasm Staging ,lcsh:RC705-779 ,Chemotherapy ,business.industry ,INDIVIDUAL PATIENT DATA ,PREOPERATIVE CHEMOTHERAPY ,Induction chemotherapy ,lcsh:Diseases of the respiratory system ,RANDOMIZED PHASE-III ,medicine.disease ,Neoadjuvant Therapy ,ddc ,Radiation therapy ,Treatment Outcome ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Locally advanced disease ,LEUKEMIA-GROUP-B ,Radiotherapy, Adjuvant ,Non small cell ,Immunotherapy ,GROWTH-FACTOR-RECEPTOR ,business ,Adjuvant - Abstract
Stage III nonsmall cell lung cancer (NSCLC) comprises about one-third of NSCLC patients and is very heterogeneous with varying and mostly poor prognosis. It is also called “locoregionally or locally advanced disease”. Due to its heterogeneity a general schematic management approach is not appropriate. Usually a combination of local therapy (surgery or radiotherapy, depending on functional, technical and oncological operability) with systemic platinum-based doublet chemotherapy and, recently, followed by immune therapy is used. A more aggressive approach of triple agent chemotherapy or two local therapies (surgery and radiotherapy, except for specific indications) has no benefit for overall survival. Until now tumour stage and the general condition of the patient are the most relevant prognostic factors. Characterising the tumour molecularly and immunologically may lead to a more personalised and effective approach. At the moment, after an exact staging and functional evaluation, an interdisciplinary discussion amongst the tumour board is warranted and offers the best management strategy.
- Published
- 2019
34. Optimal management of localized rectal cancer in older patients
- Author
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Harm J. T. Rutten, Krzysztof Bujko, Rob Glynne-Jones, Demetris Papamichael, Surgery, and RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy
- Subjects
medicine.medical_specialty ,Colorectal cancer ,medicine.medical_treatment ,Brachytherapy ,Non-operative management ,Vulnerability ,Adenocarcinoma ,03 medical and health sciences ,0302 clinical medicine ,Quality of life (healthcare) ,ADJUVANT CHEMOTHERAPY ,Older patients ,QUALITY-OF-LIFE ,Health care ,Humans ,Medicine ,SHORT-COURSE RADIOTHERAPY ,030212 general & internal medicine ,External beam radiotherapy ,Radical surgery ,Rectal cancer ,Intensive care medicine ,ELDERLY-PATIENTS ,Aged ,PREOPERATIVE RADIOTHERAPY ,Frailty ,Radiotherapy ,Rectal Neoplasms ,business.industry ,TOTAL MESORECTAL EXCISION ,Age Factors ,COMPLETE CLINICAL-RESPONSE ,Patient Preference ,RANDOMIZED PHASE-III ,medicine.disease ,Comorbidity ,Oncology ,Chemoradiation ,EXTERNAL-BEAM RADIOTHERAPY ,030220 oncology & carcinogenesis ,Older adults ,TRANSANAL ENDOSCOPIC MICROSURGERY ,Quality of Life ,Geriatrics and Gerontology ,business - Abstract
In advising the optimal management for older patients, health care professionals try to balance the risks from frailty, vulnerability, and comorbidity against the patient's ultimate prognosis, potential functional outcomes and quality of life (QOL). At the same time it is important to involve the patient and incorporate their preferences. But how can we present and balance the potential downside of radical radiotherapy and risks of unsalvageable recurrence against the potential risks of postoperative morbidity and mortality associated with radical surgery? There are currently no nationally approved and evidence-based guidelines available to ensure consistency in discussions with older adults or frail and vulnerable patients. In this overview we hope to provide an insightful discussion of the relevant issues and options currently available. (C) 2018 Elsevier Ltd. All rights reserved.
- Published
- 2018
35. Copy number load predicts outcome of metastatic colorectal cancer patients receiving bevacizumab combination therapy
- Author
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Diether Lambrechts, Hans Prenen, Miriam Koopman, Timo Gaiser, Massimiliano Mazzone, Jeroen Depreeuw, Bozena Fender, Chiara Cremolini, Neerincx Maarten, Elaine W. Kay, Annette T. Byrne, Johannes Betge, Orna Bacon, Bram Boeckx, William M. Gallagher, Ian S. Miller, Ana Barat, Bruce Moran, Cornelis J. A. Punt, Sudipto Das, Jochen H. M. Prehn, Bryan T. Hennessy, Verena Murphy, Fotios Loupakis, Henk M.W. Verheul, Dominiek Smeets, Joseph Brady, Deborah A. McNamara, Darran P. O'Connor, Nicole C.T. van Grieken, Matthias P. Ebert, Bauke Ylstra, Rut Klinger, Oncology, CCA - Cancer biology and immunology, Pathology, AGEM - Re-generation and cancer of the digestive system, Medical oncology, and VU University medical center
- Subjects
0301 basic medicine ,Oncology ,Male ,Colorectal cancer ,MICROSATELLITE INSTABILITY ,medicine.medical_treatment ,General Physics and Astronomy ,CHROMOSOMAL INSTABILITY ,Mice ,0302 clinical medicine ,Antineoplastic Agents, Immunological ,FOLFOX ,Chromosome instability ,lcsh:Science ,Multidisciplinary ,COLON-CANCER ,virus diseases ,Middle Aged ,female genital diseases and pregnancy complications ,3. Good health ,READ ALIGNMENT ,Multidisciplinary Sciences ,Bevacizumab ,Immunological ,030220 oncology & carcinogenesis ,Science & Technology - Other Topics ,CONSENSUS MOLECULAR SUBTYPES ,Female ,Colorectal Neoplasms ,Engineering sciences. Technology ,medicine.drug ,medicine.medical_specialty ,Adenocarcinoma ,Aged ,Animals ,Chromosomal Instability ,Humans ,Retrospective Studies ,Xenograft Model Antitumor Assays ,DNA Copy Number Variations ,Combination therapy ,Science ,Antineoplastic Agents ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,BURROWS-WHEELER TRANSFORM ,Internal medicine ,medicine ,neoplasms ,Chemotherapy ,Science & Technology ,business.industry ,Cancer ,Retrospective cohort study ,General Chemistry ,RANDOMIZED PHASE-III ,medicine.disease ,030104 developmental biology ,ENDOTHELIAL GROWTH-FACTOR ,lcsh:Q ,1ST-LINE THERAPY ,business ,PLUS BEVACIZUMAB - Abstract
Increased copy number alterations (CNAs) indicative of chromosomal instability (CIN) have been associated with poor cancer outcome. Here, we study CNAs as potential biomarkers of bevacizumab (BVZ) response in metastatic colorectal cancer (mCRC). We cluster 409 mCRCs in three subclusters characterized by different degrees of CIN. Tumors belonging to intermediate-to-high instability clusters have improved outcome following chemotherapy plus BVZ versus chemotherapy alone. In contrast, low instability tumors, which amongst others consist of POLE-mutated and microsatellite-instable tumors, derive no further benefit from BVZ. This is confirmed in 81 mCRC tumors from the phase 2 MoMa study involving BVZ. CNA clusters overlap with CRC consensus molecular subtypes (CMS); CMS2/4 xenografts correspond to intermediate-to-high instability clusters and respond to FOLFOX chemotherapy plus mouse avastin (B20), while CMS1/3 xenografts match with low instability clusters and fail to respond. Overall, we identify copy number load as a novel potential predictive biomarker of BVZ combination therapy., Increased copy number alterations, indicative of chromosomal instability, is associated with poor cancer outcome. Here, metastatic colorectal cancer patients displaying intermediate-high CIN associate with improved outcome following chemotherapy and bevacizumab treatment, suggesting CIN as a predictive biomarker.
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- 2018
36. Studying cancer metastasis
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CELL LUNG-CANCER ,EMBRYO CHORIOALLANTOIC MEMBRANE ,PATIENT-DERIVED XENOGRAFTS ,RANDOMIZED PHASE-III ,PANCREATIC-CANCER ,OVARIAN-CANCER ,Metastasis ,In vitro model ,MOUSE MODELS ,MATRIX-METALLOPROTEINASE INHIBITOR ,In silico model ,Animal model ,Patient derived (tumor) xenograft model ,Humanized mouse models ,ADVANCED BREAST-CANCER ,IN-VIVO ,Cancer - Abstract
Cancer metastasis causes most cancer-related deaths. Several model systems to study the complex and multi step process of metastasis exist, including in vitro systems, ex-vivo organ slices, Drosophila Melanogaster and zebrafish models and the use of the chorio allantoic membrane (CAM) of fertilized chicken eggs. These models are relatively easy and cheap but often lack the opportunity to study the complete metastasis cascade. More complex but also more expensive is the use of animal models including the more recently developed patient derived tumor xenografts (PDTX). In this review, we give an overview of the existing metastatic models, discuss the challenges of improving current models to enhance translation from the preclinical to the clinical setting and consider future perspectives. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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- 2016
37. Studying cancer metastasis: Existing models, challenges and future perspectives
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Annemiek M E Walenkamp, Denise M. S. van Marion, Hetty Timmer-Bosscha, and Urszula Domańska
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0301 basic medicine ,animal structures ,CELL LUNG-CANCER ,EMBRYO CHORIOALLANTOIC MEMBRANE ,Cancer metastasis ,Chorio allantoic membrane ,Bioinformatics ,OVARIAN-CANCER ,Metastasis ,In vitro model ,03 medical and health sciences ,Animal model ,MOUSE MODELS ,Neoplasms ,Pancreatic cancer ,MATRIX-METALLOPROTEINASE INHIBITOR ,In silico model ,Animals ,Humans ,Medicine ,ADVANCED BREAST-CANCER ,IN-VIVO ,Cancer ,business.industry ,Hematology ,PATIENT-DERIVED XENOGRAFTS ,RANDOMIZED PHASE-III ,medicine.disease ,PANCREATIC-CANCER ,Disease Models, Animal ,030104 developmental biology ,Oncology ,Patient derived (tumor) xenograft model ,Non small cell ,Humanized mouse models ,business - Abstract
Cancer metastasis causes most cancer-related deaths. Several model systems to study the complex and multi step process of metastasis exist, including in vitro systems, ex-vivo organ slices, Drosophila Melanogaster and zebrafish models and the use of the chorio allantoic membrane (CAM) of fertilized chicken eggs. These models are relatively easy and cheap but often lack the opportunity to study the complete metastasis cascade. More complex but also more expensive is the use of animal models including the more recently developed patient derived tumor xenografts (PDTX). In this review, we give an overview of the existing metastatic models, discuss the challenges of improving current models to enhance translation from the preclinical to the clinical setting and consider future perspectives. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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- 2016
38. Optimal management of localized rectal cancer in older patients
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Bujko, Krzysztof and Bujko, Krzysztof
- Abstract
In advising the optimal management for older patients, health care professionals try to balance the risks from frailty, vulnerability, and comorbidity against the patient's ultimate prognosis, potential functional outcomes and quality of life (QOL). At the same time it is important to involve the patient and incorporate their preferences. But how can we present and balance the potential downside of radical radiotherapy and risks of unsalvageable recurrence against the potential risks of postoperative morbidity and mortality associated with radical surgery? There are currently no nationally approved and evidence-based guidelines available to ensure consistency in discussions with older adults or frail and vulnerable patients. In this overview we hope to provide an insightful discussion of the relevant issues and options currently available. (C) 2018 Elsevier Ltd. All rights reserved.
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- 2018
39. Molecular-Biology-Driven Treatment for Metastatic Colorectal Cancer
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Valentino Impera, Giorgio Astara, Pina Ziranu, Andrea Pretta, Mara Persano, Elena Massa, Marco Puzzoni, Clelia Madeddu, Manuela Dettori, Giorgio Saba, Laura Demurtas, Stefano Mariani, S. Camera, Dario Spanu, Mariele Dessì, Valeria Pusceddu, Francesca Balconi, Marco Dubois, Eleonora Lai, Francesca Musio, Annagrazia Pireddu, Mario Scartozzi, Francesco Atzori, S. Tolu, Nicole Liscia, Clelia Donisi, G. Pinna, and Marco Migliari
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,MICROSATELLITE INSTABILITY ,Colorectal cancer ,medicine.medical_treatment ,Review ,Disease ,lcsh:RC254-282 ,WILD-TYPE KRAS ,molecular biomarkers ,DOUBLE-BLIND ,03 medical and health sciences ,0302 clinical medicine ,Growth factor receptor ,Internal medicine ,PROGNOSTIC-SIGNIFICANCE ,Medicine ,tailored treatment ,FOLFIRI PLUS BEVACIZUMAB ,Science & Technology ,business.industry ,metastatic colorectal cancer ,ISLAND METHYLATOR PHENOTYPE ,Microsatellite instability ,Immunotherapy ,RANDOMIZED PHASE-III ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,OPEN-LABEL ,medicine.disease ,Precision medicine ,digestive system diseases ,Clinical trial ,1ST-LINE TREATMENT ,030104 developmental biology ,030220 oncology & carcinogenesis ,therapeutic implications ,DNA mismatch repair ,GROWTH-FACTOR RECEPTOR ,business ,Life Sciences & Biomedicine - Abstract
BACKGROUND: Metastatic CRC (mCRC) is a molecular heterogeneous disease. The aim of this review is to give an overview of molecular-driven treatment of mCRC patients. METHODS: A review of clinical trials, retrospective studies and case reports was performed regarding molecular biomarkers with therapeutic implications. RESULTS: RAS wild-type status was confirmed as being crucial for anti-epidermal growth factor receptor (EGFR) monoclonal antibodies and for rechallenge strategy. Antiangiogenic therapies improve survival in first- and second-line settings, irrespective of RAS status, while tyrosine kinase inhibitors (TKIs) remain promising in refractory mCRC. Promising results emerged from anti-HER2 drugs trials in HER2-positive mCRC. Target inhibitors were successful for BRAFV600E mutant mCRC patients, while immunotherapy was successful for microsatellite instability-high/defective mismatch repair (MSI-H/dMMR) or DNA polymerase epsilon catalytic subunit (POLE-1) mutant patients. Data are still lacking on NTRK, RET, MGMT, and TGF-β, which require further research. CONCLUSION: Several molecular biomarkers have been identified for the tailored treatment of mCRC patients and multiple efforts are currently ongoing to increase the therapeutic options. In the era of precision medicine, molecular-biology-driven treatment is the key to impro patient selection and patient outcomes. Further research and large phase III trials are required to ameliorate the therapeutic management of these patients. ispartof: CANCERS vol:12 issue:5 ispartof: location:Switzerland status: published
- Published
- 2020
40. The use of single armed observational data to closing the gap in otherwise disconnected evidence networks:a network meta-analysis in multiple myeloma
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Kai Ruggeri, Joy Leahy, Michael O'Dwyer, James Morris, Cathal Walsh, Natalia Homer, Áine Maguire, Gordon Cook, Susanne Schmitz, Jack Bowden, Vanessa Buchanan, Ayesha Khan, Elisa Haller, Isla Kuhn, Schmitz, Susanne [0000-0003-4753-1709], Apollo - University of Cambridge Repository, and Celgene
- Subjects
Epidemiology ,Computer science ,Network Meta-Analysis ,treatment outcomes ,randomized phase-iii ,Dexamethasone ,law.invention ,Ixazomib ,Bortezomib ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,law ,Statistics ,Antineoplastic Combined Chemotherapy Protocols ,Network meta-analysis ,Lenalidomide ,Randomized Controlled Trials as Topic ,Single armed studies ,lcsh:R5-920 ,Medicine--Research--Data processing ,lenalidomide plus dexamethasone ,Antibodies, Monoclonal ,Relapsed or refractory myeloma ,Observational Studies as Topic ,Systematic review ,Evidence synthesis ,030220 oncology & carcinogenesis ,Meta-analysis ,lcsh:Medicine (General) ,Multiple Myeloma ,Oligopeptides ,Medicine--Research--Methodology ,medicine.drug ,Research Article ,refractory myeloma ,Bridging (networking) ,Health Informatics ,low-dose dexamethasone ,03 medical and health sciences ,Covariate ,medicine ,adjusted indirect comparisons ,Humans ,propensity score ,therapy ,Bayes Theorem ,mixed treatment comparisons ,Survival Analysis ,chemistry ,Observational study ,030215 immunology ,Systematic Reviews as Topic - Abstract
Background Network meta-analysis (NMA) allows for the estimation of comparative effectiveness of treatments that have not been studied in head-to-head trials; however, relative treatment effects for all interventions can only be derived where available evidence forms a connected network. Head-to-head evidence is limited in many disease areas, regularly resulting in disconnected evidence structures where a large number of treatments are available. This is also the case in the evidence of treatments for relapsed or refractory multiple myeloma. Methods Randomised controlled trials (RCTs) identified in a systematic literature review form two disconnected evidence networks. Standard Bayesian NMA models are fitted to obtain estimates of relative effects within each network. Observational evidence was identified to fill the evidence gap. Single armed trials are matched to act as each other’s control group based on a distance metric derived from covariate information. Uncertainty resulting from including this evidence is incorporated by analysing the space of possible matches. Results Twenty five randomised controlled trials form two disconnected evidence networks; 12 single armed observational studies are considered for bridging between the networks. Five matches are selected to bridge between the networks. While significant variation in the ranking is observed, daratumumab in combination with dexamethasone and either lenalidomide or bortezomib, as well as triple therapy of carfilzomib, ixazomib and elozumatab, in combination with lenalidomide and dexamethasone, show the highest effects on progression free survival, on average. Conclusions The analysis shows how observational data can be used to fill gaps in the existing networks of RCT evidence; allowing for the indirect comparison of a large number of treatments, which could not be compared otherwise. Additional uncertainty is accounted for by scenario analyses reducing the risk of over confidence in interpretation of results.
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- 2018
41. Long-term effects of adjunctive perampanel on cognition in adolescents with partial seizures
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Jesus Eric Piña-Garza, J. Ben Renfroe, Dinesh Kumar, Betsy Williams, Vicente Villanueva, Antonio Laurenza, Lieven Lagae, and Kimford J. Meador
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Male ,Time Factors ,CHILDREN ,PARTIAL-ONSET SEIZURES ,CHILDHOOD ABSENCE EPILEPSY ,Behavioral Neuroscience ,Perampanel ,chemistry.chemical_compound ,Epilepsy ,OPEN-LABEL EXTENSION ,DOUBLE-BLIND ,0302 clinical medicine ,Cognition ,Medicine ,Attention ,030212 general & internal medicine ,Child ,Psychiatry ,Cross-Over Studies ,ANTIEPILEPTIC DRUGS ,Memory, Short-Term ,Treatment Outcome ,Neurology ,Tolerability ,SAFETY ,Anticonvulsants ,Drug Therapy, Combination ,Female ,medicine.symptom ,Life Sciences & Biomedicine ,Behavioral Sciences ,Somnolence ,Antiepileptic drug ,medicine.medical_specialty ,Adolescent ,Pyridones ,Clinical Neurology ,Development ,Placebo ,Dizziness ,03 medical and health sciences ,Double-Blind Method ,Seizures ,Internal medicine ,VALPROIC ACID ,Nitriles ,Humans ,Partial seizures ,Science & Technology ,business.industry ,RANDOMIZED PHASE-III ,medicine.disease ,Crossover study ,Discontinuation ,ZONISAMIDE MONOTHERAPY ,chemistry ,Adjunctive treatment ,Neurology (clinical) ,Neurosciences & Neurology ,business ,030217 neurology & neurosurgery - Abstract
OBJECTIVE: The aim of this study was to evaluate long-term effects of adjunctive perampanel on cognition, efficacy, growth, safety, and tolerability in adolescents with inadequately controlled partial seizures. METHODS: Study 235, a multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase II study with an open-label extension phase (NCT01161524), was primarily designed to assess the effects of adjunctive perampanel on cognition. Patients (aged ≥12 to
- Published
- 2018
42. Risk Factors for Fatal Pulmonary Hemorrhage following Concurrent Chemoradiotherapy in Stage 3B/C Squamous-Cell Lung Carcinoma Patients
- Author
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Alper Findikcioglu, Ozgur Ozyilkan, Huseyin Mertsoylu, Ozan Cem Guler, Yurday Ozdemir, Berna Akkus Yildirim, Berrin Pehlivan, Ali Ayberk Besen, Ugur Selek, Erkan Topkan, Selek, Uğur (ORCID 0000-0001-8087-3140 & YÖK ID 27211), Topkan, Erkan, Özdemir, Yurday, Besen, Ali A., Güler, Ozan C., Yıldırım, Berna A., Mertsoylu, Hüseyin, Fındıkçıoğlu, Alper, Özyılkan, Özgür, Pehlivan, Berrin, School of Medicine, and Department of Radiation Oncology
- Subjects
medicine.medical_specialty ,BODY RADIATION-THERAPY ,Article Subject ,medicine.medical_treatment ,BEVACIZUMAB ,Medicine ,Oncology ,Body radiation-therapy ,Randomized phase-III ,Massive hemoptysis ,Cancer-patients ,Radiotherapy ,Trial ,Brachytherapy ,Bevacizumab ,Chemoradiation ,Chemotherapy ,CANCER-PATIENTS ,Gastroenterology ,lcsh:RC254-282 ,CHEMORADIATION ,03 medical and health sciences ,Basal (phylogenetics) ,0302 clinical medicine ,Internal medicine ,Carcinoma ,medicine ,030212 general & internal medicine ,Stage (cooking) ,MASSIVE HEMOPTYSIS ,Lung ,BRACHYTHERAPY ,business.industry ,Incidence (epidemiology) ,Medical record ,RANDOMIZED PHASE-III ,CHEMOTHERAPY ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Radiation therapy ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,TRIAL ,Pulmonary hemorrhage ,business ,RADIOTHERAPY ,Research Article - Abstract
We aimed to identify the fatal pulmonary hemorrhage- (FPH-) related risk factors in stage 3B/C squamous-cell lung carcinoma (SqCLC) patients treated with definitive concurrent chemoradiotherapy (C-CRT). Medical records of 505 stage 3B/C SqCLC patients who underwent 66 Gy radiotherapy plus 1-3 cycles of concurrent chemotherapy with available pretreatment thoracic computerized tomography scans were retrospectively analyzed. Primary end-point was the identification of FPH-related risk factors. Examined factors included the basal patient and tumor characteristics with specific emphasis on the tumor cavitation (TC) status, tumor size (TS) and cavitation size (CS), tumor volume and cavitation volume (TV and CV), relative cavitation size (RCS = CS/Ts), and relative cavitation volume (RCV=CV/TV). FPH emerged in 13 (2.6%) patients, with 12 (92.3%) of them being diagnosed 0.14 (37.5% versus 11.1% for RCV 0.14. Diagnosis of >90% FPHs, NA
- Published
- 2018
- Full Text
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43. A Case of Lenvatinib-Induced Focal Segmental Glomerulosclerosis (FSGS) in Metastatic Medullary Thyroid Cancer
- Author
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Fleming, Kathryn, McGuinness, James, Kipgen, David, Glen, Hilary, and Spiliopoulou, Pavlina
- Subjects
Science & Technology ,CELL LUNG-CANCER ,Case Report ,VEGF INHIBITION ,RANDOMIZED PHASE-III ,INTERSTITIAL NEPHRITIS ,ANGIOGENESIS INHIBITION ,urologic and male genital diseases ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,lcsh:RC254-282 ,female genital diseases and pregnancy complications ,COLORECTAL-CANCER ,Oncology ,ADVANCED SOLID TUMORS ,THROMBOTIC MICROANGIOPATHY ,ENDOTHELIAL GROWTH-FACTOR ,TYROSINE KINASE INHIBITOR ,Life Sciences & Biomedicine - Abstract
We describe a case of lenvatinib (E7080) associated focal segmental glomerulosclerosis (FSGS) encountered during the treatment of metastatic medullary thyroid cancer. Proteinuria is a relatively common side effect of VEGF-targeted treatments and can occasionally result in treatment discontinuation. Here, we describe a patient who developed secondary FSGS necessitating discontinuation of treatment at first but who was subsequently rechallenged with anti-VEGF-targeted treatment without recurrence of proteinuria. Lenvatinib was a novel experimental agent at the time the treatment took place; however, its recent licensing for the treatment of thyroid malignancies in the UK makes reporting of these adverse effects all the more important now.
- Published
- 2018
44. Immune checkpoint inhibitors for advanced non-small cell lung cancer: emerging sequencing for new treatment targets
- Author
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Hakaru Tadokoro, Pedro Nazareth Aguiar, Ramon Andrade de Mello, Gilberto Lopes, Jahan C. Penny-Dimri, Luke A Perry, and Carmelia Maria Noia Barreto
- Subjects
0301 basic medicine ,atezolizumab ,Cancer Research ,Lymphocyte ,medicine.medical_treatment ,Population ,Maintenance bevacizumab ,Next-generation ,Pembrolizumab ,Review ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Atezolizumab ,Pd-L1 expression ,medicine ,Open-label ,education ,Lung cancer ,Comparing cisplatin ,non-small cell lung cancer ,nivolumab ,education.field_of_study ,Chemotherapy ,Stage Iiib ,Immunotherapy ,medicine.disease ,Randomized phase-Iii ,Predictive biomarker ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Updated survival analysis ,030220 oncology & carcinogenesis ,Immunology ,Cancer research ,Antitumor-activity ,immunotherapy ,pembrolizumab ,Nivolumab - Abstract
Lung cancer is the leading cause of cancer-related deaths in the world. Immune checkpoint inhibitors (ICI) stimulate cytotoxic lymphocyte activity against tumour cells. These agents are available for the treatment of nonsmall cell lung cancer (NSCLC) after failure of platinumbased therapy. One recent study has demonstrated that ICI monotherapy was superior to platinum-based chemotherapy for first-line treatment. Nevertheless, this benefit was only for a minority of the population (30%) whose tumour programmed death receptor ligand-1 (PD-L1) expression was above 50%. Therefore, several strategies are under investigation. One option for patients with PD-L1 expression lower than 50% may be the combination of ICI with platinum-based chemotherapy or with ICIs against different targets. However, all of these combinations are at an early stage of investigation and may be very expensive or toxic, producing several harmful adverse events. info:eu-repo/semantics/publishedVersion
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- 2017
45. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel
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Hervé Dombret, Miguel A. Sanz, Hartmut Döhner, Martin S. Tallman, Frederick R. Appelbaum, David Grimwade, Gert J. Ossenkoppele, Hwei-Fang Tien, Benjamin L. Ebert, Thomas Büchner, Dietger Niederwieser, Elihu H. Estey, Richard A. Larson, Bob Löwenberg, Andrew H. Wei, Francesco Lo-Coco, Jorge Sierra, Sergio Amadori, Tomoki Naoe, Clara D. Bloomfield, Ross L. Levine, Pierre Fenaux, CCA - Cancer Treatment and quality of life, and Hematology
- Subjects
Pathology ,Neoplasm, Residual ,International Cooperation ,Disease ,Review Article ,Biochemistry ,European LeukemiaNet ,0302 clinical medicine ,Risk Factors ,hemic and lymphatic diseases ,CONVENTIONAL CARE REGIMENS ,Disease management (health) ,medicine.diagnostic_test ,ACUTE MYELOGENOUS LEUKEMIA ,Hematopoietic Stem Cell Transplantation ,Disease Management ,SINGLE CEBPA MUTATIONS ,Hematology ,1ST COMPLETE REMISSION ,HIGH-DOSE CYTARABINE ,Leukemia, Myeloid, Acute ,Treatment Outcome ,030220 oncology & carcinogenesis ,Practice Guidelines as Topic ,Adult ,medicine.medical_specialty ,Consensus ,Immunology ,BUSULFAN PLUS CYCLOPHOSPHAMIDE ,MEDLINE ,MINIMAL RESIDUAL DISEASE ,Antineoplastic Agents ,ACUTE MYELOID-LEUKEMIA ,Enasidenib ,Transplantation, Autologous ,Drug Administration Schedule ,Immunophenotyping ,03 medical and health sciences ,medicine ,Humans ,Genetic Testing ,Intensive care medicine ,Genetic testing ,business.industry ,STEM-CELL TRANSPLANTATION ,Cell Biology ,RANDOMIZED PHASE-III ,Minimal residual disease ,Transplantation ,business ,Settore MED/15 - Malattie del Sangue ,030215 immunology - Abstract
The first edition of the European LeukemiaNet (ELN) recommendations for diagnosis and management of acute myeloid leukemia (AML) in adults, published in 2010, has found broad acceptance by physicians and investigators caring for patients with AML. Recent advances, for example, in the discovery of the genomic landscape of the disease, in the development of assays for genetic testing and for detecting minimal residual disease (MRD), as well as in the development of novel antileukemic agents, prompted an international panel to provide updated evidence- and expert opinion-based recommendations. The recommendations include a revised version of the ELN genetic categories, a proposal for a response category based on MRD status, and criteria for progressive disease.
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- 2017
46. Is more better? The impact of extended adjuvant temozolomide in newly diagnosed glioblastoma: a secondary analysis of EORTC and NRG Oncology/RTOG
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Minesh P. Mehta, Martin J. van den Bent, Do Hyun Nam, Mark R. Gilbert, L. Burt Nabors, Paul D. Brown, René O. Mirimanoff, Monika E. Hegi, Peixin Zhang, Vassilis Golfinopoulos, Benjamin W. Corn, Thierry Gorlia, Roger Stupp, Brigitta G. Baumert, James Perry, David A. Reardon, Warren P. Mason, Michael Weller, Michelle M. Kim, Deborah T. Blumenthal, Sara C. Erridge, Neurology, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Radiotherapie, University of Zurich, and Blumenthal, Deborah T
- Subjects
0301 basic medicine ,Oncology ,Male ,Cancer Research ,TOXICITY ,0302 clinical medicine ,Maintenance therapy ,Medicine ,1306 Cancer Research ,GRADE GLIOMAS ,Aged, 80 and over ,MOLECULAR-MECHANISMS ,Brain Neoplasms ,Standard treatment ,Middle Aged ,OPEN-LABEL ,Combined Modality Therapy ,Dacarbazine ,2728 Neurology (clinical) ,Editorial ,030220 oncology & carcinogenesis ,Disease Progression ,2730 Oncology ,TRIAL ,Female ,medicine.drug ,RADIOTHERAPY ,Adult ,medicine.medical_specialty ,STANDARD TREATMENT ,Bevacizumab ,BEVACIZUMAB ,610 Medicine & health ,Disease-Free Survival ,03 medical and health sciences ,Internal medicine ,Temozolomide ,Humans ,Antineoplastic Agents, Alkylating ,Aged ,Performance status ,business.industry ,Tumor Suppressor Proteins ,O-6-methylguanine-DNA methyltransferase ,RANDOMIZED PHASE-III ,10040 Clinic for Neurology ,MALIGNANT GLIOMAS ,Regimen ,030104 developmental biology ,Neurology (clinical) ,business ,Glioblastoma - Abstract
BACKGROUND: Following maximal safe resection, radiation (RT) with concurrent and 6 cycles (C) of adjuvant temozolomide (TMZ) [Stupp NEJM 2005] has been established as standard of care for newly-diagnosed glioblastoma (GBM). This regimen has been adopted with variations, including extending TMZ beyond 6 cycles. The optimal duration of maintenance therapy remains a matter of debate. OBJECTIVES: Compare outcomes of patients who completed 6C of TMZ and discontinued treatment to those of patients who continued TMZ >6C. METHODOLOGY: We performed a pooled analysis of 4 randomized trials (EORTC/NCIC 26981-CE.3; EORTC26071-CENTRIC; EMD-CORE; RTOG 0525-Intergroup). All patients received the standard of care (TMZ/RT with TMZ). All patients who completed TMZ 6C and had not progressed within 28 days were included. Based on local practice and the discretion of the investigator TMZ could be continued for up to 12C. Patients were grouped into those who completed 6C TMZ and those who continued >6C; progression-free and overall survival were analyzed, adjusted by age, performance status, resection extent, and MGMT status. Exploratory analyses with and without MGMT data imputation were performed at 5% significance. RESULTS: Independent of evaluated prognostic factors, treatment with >6C TMZ was significantly associated with improved PFS [HR 0.77 (0.61-0.97), p = 0.03]. This effect was more pronounced in patients with methylated MGMT [HR 0.64 (0.47-0.88), p 6C groups were well-balanced, except MGMT methylation status; methylated status was less frequent in patients receiving >6C (39% vs 62%). Prognostic factors including age, MGMT methylation, extent of resection, and performance status had an expected impact on outcomes. CONCLUSION: Increasing the number of cycles of TMZ beyond 6 months is not shown to increase OS. PFS was improved, more so in patients with MGMT-methylated tumors.
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- 2017
47. Comparison between MRI and pathology in the assessment of tumour regression grade in rectal cancer
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Francesco Sclafani, Bengt Glimelius, Diana Tait, Ian Chau, Ruwaida Begum, Susana Roselló, Josep Tabernero, Larissa Sena Teixeira Mendes, Andrew Wotherspoon, Jacqui Oates, David Cunningham, Jessica Evans, Janet Thomas, Svetlana Balyasnikova, Gina Brown, Clare Peckitt, and NIHR
- Subjects
Male ,Cancer Research ,Pathology ,SURGERY ,Colorectal cancer ,ACCURACY ,medicine.medical_treatment ,Magnetic resonance tumour regression grade ,PREOPERATIVE CHEMORADIATION ,Kaplan-Meier Estimate ,THERAPY ,030218 nuclear medicine & medical imaging ,0302 clinical medicine ,Interquartile range ,Rectal cancer ,Neoadjuvant therapy ,Aged, 80 and over ,COMPLETE RESPONSE ,medicine.diagnostic_test ,Middle Aged ,Magnetic Resonance Imaging ,Neoadjuvant Therapy ,Oncology ,030220 oncology & carcinogenesis ,Female ,Radiology ,Life Sciences & Biomedicine ,RADIOTHERAPY ,Adult ,medicine.medical_specialty ,Cytodiagnosis ,magnetic resonance tumour regression grade ,Disease-Free Survival ,03 medical and health sciences ,Clinical Trials, Phase II as Topic ,medicine ,Pathological tumour regression grade ,Humans ,Oncology & Carcinogenesis ,rectal cancer ,Pathological ,pathological tumour regression grade ,Aged ,Neoplasm Staging ,Science & Technology ,Rectal Neoplasms ,business.industry ,TOTAL MESORECTAL EXCISION ,Magnetic resonance imaging ,Chemoradiotherapy, Adjuvant ,RANDOMIZED PHASE-III ,NEOADJUVANT CHEMORADIOTHERAPY ,medicine.disease ,Clinical trial ,Radiation therapy ,Clinical Study ,FOLLOW-UP ,business ,1112 Oncology And Carcinogenesis ,Chemoradiotherapy - Abstract
Background: Limited data exist regarding the correlation between MRI tumour regression grade (mrTRG) and pathological TRG (pTRG) in rectal cancer. Methods: mrTRG and pTRG were compared in rectal cancer patients from two phase II trials (EXPERT and EXPERT-C). The agreement between radiologist and pathologist was assessed with the weighted κ test while the Kaplan–Meier method was used to estimate survival outcomes. Results: One hundred ninety-one patients were included. Median time from completion of neoadjuvant treatment to pre-operative MRI and surgery was 4.1 weeks (interquartile range (IQR): 3.7–4.7) and 6.6 weeks (IQR: 5.9–7.6), respectively. Fair agreement was found between mrTRG and pTRG when regression was classified according to standard five-tier systems (κ=0.24) or modified three-tier systems (κ=0.25). Sensitivity and specificity of mrTRG 1–2 (complete/good radiological regression) for the prediction of pathological complete response was 74.4% (95% CI: 58.8–86.5) and 62.8% (95% CI: 54.5–70.6), respectively. Survival outcomes of patients with intermediate pathological regression (pTRG 2) were numerically better if complete/good regression was also observed on imaging (mrTRG 1–2) compared to poor regression (mrTRG 3–5) (5-year recurrence-free survival 76.9% vs 65.9%, P=0.18; 5-year overall survival 80.6% vs 68.8%, P=0.22). Conclusions: The agreement between mrTRG and pTRG is low and mrTRG cannot be used as a surrogate of pTRG. Further studies are warranted to assess the ability of mrTRG to identify pathological complete responders for the adoption of non-operative management strategies and to provide complementary prognostic information to pTRG for better risk-stratification after surgery.
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- 2017
48. Evaluation of short-course radiotherapy followed by neoadjuvant bevacizumab, capecitabine, and oxaliplatin and subsequent radical surgical treatment in primary stage IV rectal cancer
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Iris D. Nagtegaal, C.J.H. van de Velde, T. H. van Dijk, Klaas Havenga, de Koert Jong, Geerard L. Beets, J. C. Beukema, T. Wiggers, H.J.T. Rutten, A. J. Gelderblom, K. Tamas, Geesiena Hospers, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Targeted Gynaecologic Oncology (TARGON), Faculteit Medische Wetenschappen/UMCG, Groningen Institute for Organ Transplantation (GIOT), Surgery, RS: NUTRIM - R2 - Gut-liver homeostasis, and RS: GROW - School for Oncology and Reproduction
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Male ,Organoplatinum Compounds ,Colorectal cancer ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Deoxycytidine ,Antineoplastic Combined Chemotherapy Protocols ,Neoadjuvant therapy ,Liver Neoplasms ,Hematology ,Middle Aged ,CHEMOTHERAPY ,Neoadjuvant Therapy ,Oxaliplatin ,Treatment Outcome ,Oncology ,Chemotherapy, Adjuvant ,Female ,DELAYED SURGERY ,TRIAL ,Fluorouracil ,medicine.drug ,neoadjuvant chemotherapy ,Adult ,medicine.medical_specialty ,Bevacizumab ,preoperative radiotherapy ,Urology ,HEPATIC RESECTION ,Adenocarcinoma ,bevacizumab ,Antibodies, Monoclonal, Humanized ,Preoperative care ,Capecitabine ,stage IV ,Translational research [ONCOL 3] ,RADIATION-THERAPY ,medicine ,Humans ,RADIOFREQUENCY ABLATION ,rectal cancer ,RECURRENCE ,Survival rate ,Aged ,Neoplasm Staging ,Rectal Neoplasms ,business.industry ,Rectum ,RANDOMIZED PHASE-III ,medicine.disease ,Surgery ,Radiation therapy ,COLORECTAL LIVER METASTASES ,Radiotherapy, Adjuvant ,Dose Fractionation, Radiation ,Neoplasm Recurrence, Local ,business - Abstract
Contains fulltext : 118397pub.pdf (Publisher’s version ) (Closed access) BACKGROUND: To evaluate the efficacy and tolerability of preoperative short-course radiotherapy followed by capecitabine and oxaliplatin treatment in combination with bevacizumab and subsequent radical surgical treatment of all tumor sites in patients with stage IV rectal cancer. PATIENTS AND METHODS: Adults with primary metastasized rectal cancer were enrolled. They received radiotherapy (5 x 5 Gy) followed by bevacizumab (7.5 mg/kg, day 1) and oxaliplatin (130 mg/m(2), day 1) intravenously and capecitabine (1000 mg/m(2) twice daily orally, days 1-14) for up to six cycles. Surgery was carried out 6-8 weeks after the last bevacizumab dose. The percentage of radical surgical treatment, 2-year survival and recurrence rates, and treatment-related toxicity was evaluated. RESULTS: Of 50 included patients, 42 (84%) had liver metastases, 5 (10%) lung metastases, and 3 (6%) both liver and lung metastases. Radical surgical treatment was possible in 36 (72%) patients. The 2-year overall survival rate was 80% [95% confidence interval (CI) 66.3%-90.0%]. The 2-year recurrence rate was 64% (95% CI 49.8%-84.5%). Toxic effects were tolerable. No treatment-related deaths occurred. CONCLUSIONS: Radical surgical treatment of all tumor sites carried out after short-course radiotherapy, and bevacizumab-capecitabine-oxaliplatin combination therapy is a feasible and potentially curative approach in primary metastasized rectal cancer.
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- 2013
49. Maintaining success, reducing treatment burden, focusing on survivorship
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late toxic effects ,treatment ,consensus conference ,diagnosis ,LONG-TERM SURVIVORS ,long-term follow-up ,RANDOMIZED PHASE-III ,STAGE-I SEMINOMA ,TESTICULAR CANCER ,LYMPH-NODE DISSECTION ,RISK-ADAPTED TREATMENT ,HIGH-DOSE CHEMOTHERAPY ,POSITRON-EMISSION-TOMOGRAPHY ,CISPLATIN-BASED CHEMOTHERAPY ,germ-cell cancer ,FOLLOW-UP - Abstract
In November 2011, the Third European Consensus Conference on Diagnosis and Treatment of Germ-Cell Cancer (GCC) was held in Berlin, Germany. This third conference followed similar meetings in 2003 (Essen, Germany) and 2006 (Amsterdam, The Netherlands) [Schmoll H-J, Souchon R, Krege S et al. European consensus on diagnosis and treatment of germ-cell cancer: a report of the European Germ-Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15: 1377-1399; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 2008; 53: 478-496; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part II. Eur Urol 2008; 53: 497-513]. A panel of 56 of 60 invited GCC experts from all across Europe discussed all aspects on diagnosis and treatment of GCC, with a particular focus on acute and late toxic effects as well as on survivorship issues.The panel consisted of oncologists, urologic surgeons, radiooncologists, pathologists and basic scientists, who are all actively involved in care of GCC patients. Panelists were chosen based on the publication activity in recent years. Before the meeting, panelists were asked to review the literature published since 2006 in 20 major areas concerning all aspects of diagnosis, treatment and follow-up of GCC patients, and to prepare an updated version of the previous recommendations to be discussed at the conference. In addition, similar to 50 E-vote questions were drafted and presented at the conference to address the most controversial areas for a poll of expert opinions. Here, we present the main recommendations and controversies of this meeting. The votes of the panelists are added as online supplements.
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- 2013
50. Maintaining success, reducing treatment burden, focusing on survivorship: highlights from the third European consensus conference on diagnosis and treatment of germ-cell cancer
- Author
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M. De Santis, Renske Altena, Friedemann Honecker, Leendert H. J. Looijenga, J. T. Hartmann, Aleksander Giwercman, R. de Wit, Silke Gillessen, Nicola Nicolai, Thomas Powles, Sophie D. Fosså, Giovanni Rosti, Robert Huddart, Alv A. Dahl, Gabriella Cohn-Cedermark, Jean-Pierre Lotz, Mark Schrader, M.P. Laguna, Gedske Daugaard, T. Tandstad, Richard Cathomas, S. Kliesch, Janine Nuver, Rainer Souchon, Jan Oldenburg, J. W. Oosterhuis, Alan Horwich, Roberto Salvioni, Frank Mayer, Martin Fenner, Andrea Necchi, S. Schweyer, C. Wittekind, Aude Flechon, Peter Albers, Susanne Krege, Jorge Aparicio, Carsten Bokemeyer, Noel W. Clarke, E. Rajpert-De Meyts, Jonas Busch, Klaus-Peter Dieckmann, Jörg Beyer, Axel Heidenreich, M. de Wit, K. Oechsle, U. De Giorgi, Aslam Sohaib, Jourik A. Gietema, Oliver Rick, Anja Lorch, C. Winter, Karim Fizazi, Felix Sedlmayer, Christian Kollmannsberger, J. R. Germá Lluch, Eva Cavallin-Ståhl, J. Claßen, Marcus Hentrich, Medical Oncology, Pathology, Beyer, J, Albers, P, Altena, R, Aparicio, J, Bokemeyer, C, Busch, J, Cathomas, R, Cavallin-Stahl, E, Clarke, Nw, Classen, J, Cohn-Cedermark, G, Dahl, Aa, Daugaard, G, De Giorgi, U, De Santis, M, De Wit, M, De Wit, R, Dieckmann, Kp, Fenner, M, Fizazi, K, Flechon, A, Fossa, Sd, Lluch, Jrg, Gietema, Ja, Gillessen, S, Giwercman, A, Hartmann, Jt, Heidenreich, A, Hentrich, M, Honecker, F, Horwich, A, Huddart, Ra, Kliesch, S, Kollmannsberger, C, Krege, S, Laguna, Mp, Looijenga, Lhj, Lorch, A, Lotz, Jp, Mayer, F, Necchi, A, Nicolai, N, Nuver, J, Oechsle, K, Oldenburg, J, Oosterhuis, Jw, Powles, T, Rajpert-De Meyts, E, Rick, O, Rosti, G, Salvioni, R, Schrader, M, Schweyer, S, Sedlmayer, F, Sohaib, A, Souchon, R, Tandstad, T, Winter, C, and Wittekind, C
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medicine.medical_specialty ,consensus conference ,diagnosis ,MEDLINE ,Reviews ,long-term follow-up ,TESTICULAR CANCER ,HIGH-DOSE CHEMOTHERAPY ,POSITRON-EMISSION-TOMOGRAPHY ,Quality of life (healthcare) ,SDG 3 - Good Health and Well-being ,Survivorship curve ,medicine ,Reproductive health ,Gynecology ,late toxic effects ,treatment ,business.industry ,LONG-TERM SURVIVORS ,Treatment burden ,Consensus conference ,Hematology ,RANDOMIZED PHASE-III ,STAGE-I SEMINOMA ,LYMPH-NODE DISSECTION ,RISK-ADAPTED TREATMENT ,Germ cell cancer ,Oncology ,Family medicine ,CISPLATIN-BASED CHEMOTHERAPY ,Survivorship Issues ,germ-cell cancer ,FOLLOW-UP ,business - Abstract
In November 2011, the Third European Consensus Conference on Diagnosis and Treatment of Germ-Cell Cancer (GCC) was held in Berlin, Germany. This third conference followed similar meetings in 2003 (Essen, Germany) and 2006 (Amsterdam, The Netherlands) [Schmoll H-J, Souchon R, Krege S et al. European consensus on diagnosis and treatment of germ-cell cancer: a report of the European Germ-Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15: 1377-1399; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 2008; 53: 478-496; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part II. Eur Urol 2008; 53: 497-513]. A panel of 56 of 60 invited GCC experts from all across Europe discussed all aspects on diagnosis and treatment of GCC, with a particular focus on acute and late toxic effects as well as on survivorship issues. The panel consisted of oncologists, urologic surgeons, radiooncologists, pathologists and basic scientists, who are all actively involved in care of GCC patients. Panelists were chosen based on the publication activity in recent years. Before the meeting, panelists were asked to review the literature published since 2006 in 20 major areas concerning all aspects of diagnosis, treatment and follow-up of GCC patients, and to prepare an updated version of the previous recommendations to be discussed at the conference. In addition, similar to 50 E-vote questions were drafted and presented at the conference to address the most controversial areas for a poll of expert opinions. Here, we present the main recommendations and controversies of this meeting. The votes of the panelists are added as online supplements.
- Published
- 2013
Catalog
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