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Objective: The aim of this study was to establish and validate a clinical prediction model for assessing the risk of metastasis and patient survival in Ewing's sarcoma (ES).Methods: Patients diagnosed with ES from the Surveillance, Epidemiology and End Results (SEER) database for the period 2010-2016 were extracted, and the data after exclusion of vacant terms was used as the training set (n=767). Prediction models predicting patients' overall survival (OS) at 1 and 3 years were created by cox regression analysis and visualized using Nomogram and web calculator. Multicenter data from four medical institutions were used as the validation set (n=51), and the model consistency was verified using calibration plots, and receiver operating characteristic (ROC) verified the predictive ability of the model. Finally, a clinical decision curve was used to demonstrate the clinical utility of the model.Results: The results of multivariate cox regression showed that age, , bone metastasis, tumor size, and chemotherapy were independent prognostic factors of ES patients. Internal and external validation results: calibration plots showed that the model had a good agreement for patient survival at 1 and 3 years; ROC showed that it possessed a good predictive ability and clinical decision curve proved that it possessed good clinical utility.Conclusions: The tool built in this paper to predict 1- and 3-year survival in ES patients ( https://drwenleli0910.shinyapps.io/EwingApp/ ) has a good identification and predictive power. [ABSTRACT FROM AUTHOR]

Background: The residual effects of cancer and its treatment can profoundly affect women's quality of life. This paper presents results from a multisite randomized controlled trial that evaluated the clinical benefits of an e-health enabled health promotion intervention (the Women's Wellness after Cancer Program or WWACP) on the health-related quality of life of women recovering from cancer treatment.Methods: Overall, 351 women previously treated for breast, blood or gynaecological cancers were randomly allocated to the intervention (WWACP) or usual care arms. The WWACP comprised a structured 12-week program that included online coaching and an interactive iBook that targeted physical activity, healthy diet, stress and menopause management, sexual wellbeing, smoking cessation, alcohol intake and sleep hygiene. Data were collected via a self-completed electronic survey at baseline (t0), 12 weeks (post-intervention, t1) and 24 weeks (to assess sustained behaviour change, t2). The primary outcome, health-related quality of life (HRQoL), was measured using the Short Form Health Survey (SF-36).Results: Following the 12-week lifestyle program, intervention group participants reported statistically significant improvements in general health, bodily pain, vitality, and global physical and mental health scores. Improvements were also noted in the control group across several HRQoL domains, though the magnitude of change was less.Conclusions: The WWACP was associated with improved HRQoL in women previously treated for blood, breast, and gynaecological cancers. Given how the synergy of different lifestyle factors influence health behaviour, interventions accounting for the reciprocity of multiple health behaviours like the WWACP, have real potential for immediate and sustainable change.Trial Registration: The protocol for this randomised controlled trial was submitted to the Australian and New Zealand Clinical Trials Registry on 15/07/2014 and approved on 28/07/2014 ( ACTRN12614000800628 ). [ABSTRACT FROM AUTHOR]

Background: Impaired physical function due to chemotherapy-induced peripheral neuropathy (CIPN) symptoms may lead to diminished quality of life. However, even with the knowledge of the effects of CIPN on physical function, clinicians infrequently assess and manage CIPN. Interventions that prioritize the early identification of CIPN to provide prompt treatment may reduce the impact of CIPN on physical function. The purpose of this paper is to compare self-reported physical function in individuals receiving neurotoxic chemotherapy between Electronic Symptom Assessment-Cancer (ESRA-C) intervention group (e.g., opportunity for symptom screening, self-care recommendations, communication coaching, and symptom tracking) and control group participants (i.e., electronic assessment alone). Secondary outcomes include pain intensity, sensory/motor CIPN, depression, fatigue, and insomnia.Methods: The data used in this paper are a subset of a randomized controlled trial that examined the impact of the ESRA-C intervention on symptom distress in individuals receiving cancer treatment. Since the interest in this analysis is on the effects of neurotoxic chemotherapy on physical function, subjects were included if they received platinum and/or taxane-based chemotherapy and completed the baseline and end-of-treatment measures. Participants completed standardized questionnaires of physical function, CIPN, fatigue, depression, pain intensity, and insomnia prior to treatment, 3-6 weeks after treatment initiation, and after the completion of treatment. Changes in mean scores are compared between groups using linear mixed models adjusting for age.Results: Intervention group participants reported significantly less reduction in physical functioning (baseline: 87.4/100; end-of-treatment: 84.5/100) relative to the control (baseline: 90.2/100; end-of-treatment: 81.8/100) (p = 0.011). For secondary measures, significantly less depression (p = 0.005) was observed in the intervention group as compared to the control, but otherwise, there were no between-group differences. Among participants who received high cumulative doses of neurotoxic chemotherapy, the intervention group reported significantly less severe sensory (p = 0.007) and motor CIPN (p = 0.039) relative to the control.Conclusion: Use of the ESRA-C intervention led to less reduction in physical function in comparison to the control in individuals receiving neurotoxic chemotherapy. Further research is needed to confirm our findings and to identify how electronic symptom assessment technology may mediate physical function preservation.Trial Registration: ClinicalTrials.Gov NCT00852852 . Registered 27 February 2009. [ABSTRACT FROM AUTHOR]

Background: Melanoma incidence has quadrupled since 1970 and melanoma is now the second most common cancer in individuals under 50. Targeted immunotherapies for melanoma now potentially enable long-term remission even in advanced melanoma, but these melanoma survivors require ongoing surveillance, with implications for NHS resources and significant social and psychological consequences for patients. Total skin self-examination (TSSE) can detect recurrence earlier and improve clinical outcomes but is underperformed in the UK. To support survivors, the Achieving Self-directed Integrated Cancer Aftercare (ASICA) intervention was developed to prompt and improve TSSE performance, with subsequent reporting of concerns and submission of skin photos to a Dermatology Nurse Practitioner (DNP). ASICA was delivered as a randomized pilot trial.Methods: This paper reports on process evaluation. Data on participants' demographics and the concerns they reported during the trial were tabulated and displayed using Microsoft Excel and SPSS. We explored which participants used ASICA, and how frequently, to report any skin concerns. We also determined how the interactions had worked in terms of quality of skin photographs submitted, clinical assessments made by the DNP, and the assessments and decisions made for each concern. Finally, we explored significant events occurring during the trial. Data on participants' demographics and the concerns they reported during the trial were tabulated and displayed using SPSS. A semi-structured interview was undertaken with the DNP to gain perspective on the range of concerns presented and how they were resolved.Results: Of 121 recruited melanoma patients receiving ASICA for 12 months, 69 participants submitted a total of 123 reports detailing 189 separate skin-related concerns and including 188 skin photographs. Where participants fully complied with follow-up by the DNP, concerns were usually resolved remotely, but 19 (10.1%) were seen at a secondary care clinic and 14 (7.4%) referred to their GP. 49 (25.9%) of concerns were not completely resolved due to partial non-compliance with DNP follow-up.Conclusion: Melanoma patients randomized to the ASICA intervention were able to report skin-related concerns that could be resolved remotely through interaction with a DNP. Feasibility issues highlighted by ASICA will support further development and optimization of this digital tool.Trial Registration: Clinical Trials.gov , NCT03328247 . Registered on 1 November 2017. [ABSTRACT FROM AUTHOR]

Background: The Sarcoma Policy Checklist was created by a multidisciplinary expert group to provide policymakers with priority areas to improve care for sarcoma patients.Main Body: This paper draws on this research, by looking more closely at how France, Germany, Italy, Spain, Sweden and the United Kingdom are addressing each of these priority areas. It aims to highlight key gaps in research, policy and practice, as well as ongoing initiatives that may impact the future care of sarcoma patients in different European countries. A pragmatic review of the published and web-based literature was undertaken. Telephone interviews were conducted in each country with clinical and patient experts to substantiate findings. Research findings were discussed within the expert group and developed into five core policy recommendations. The five identified priority areas were: the development of designated and accredited centres of reference; more professional training; multidisciplinary care; greater incentives for research and innovation; and more rapid access to effective treatments. Most of the countries studied have ongoing initiatives addressing many of these priorities; however, many are in early stages of development, or require additional funding and resources.Conclusion: Gaps in access to quality care are particularly concerning in many of Europe's lower-resourced countries. Equitable access to information, clinical trials, innovative treatments and quality specialist care should be available to all sarcoma patients. Achieving this across Europe will require close collaboration between all stakeholders at both the national and European level. [ABSTRACT FROM AUTHOR]

Background: Accounting for patients' perspective has become increasingly important. Based on the Consumer Quality Index method (founded on Consumer Assessment of Healthcare Providers and Systems) a questionnaire was recently developed for Dutch cancer patients. As a next step, this study aimed to adapt and pilot this questionnaire for international comparison of cancer patients experience and satisfaction with care in six European countries.Method: The Consumer Quality Index was translated into the local language at the participating pilot sites using cross-translation. A minimum of 100 patients per site were surveyed through convenience sampling. Data from seven pilot sites in six countries was collected through an online and paper-based survey. Internal consistency was tested by calculating Cronbach's alpha and validity by means of cognitive interviews. Demographic factors were compared as possible influencing factors.Results: A total of 698 patients from six European countries filled the questionnaire. Cronbach's alpha was good or satisfactory in 8 out of 10 categories. Patient satisfaction significantly differed between the countries. We observed no difference in patient satisfaction for age, gender, education, and tumor type, but satisfaction was significantly higher in patients with a higher level of activation.Conclusion: This European Cancer Consumer Quality Index(ECCQI) showed promising scores on internal consistency (reliability) and a good internal validity. The ECCQI is to our knowledge the first to measure and compare experiences and satisfaction of cancer patients on an international level, it may enable healthcare providers to improve the quality of cancer care. [ABSTRACT FROM AUTHOR]

Background: Rising cancer incidence, the cost of cancer pharmaceuticals and the introduction of the Cancer Drugs Fund in England, but not other United Kingdom(UK) countries means evidence of 'postcode prescribing' in cancer is important. There have been no systematic reviews considering access to cancer drugs by geographical characteristics in the UK.Methods: Studies describing receipt of cancer drugs, according to healthcare boundaries (e.g. cancer network [UK]) were identified through a systematic search of electronic databases and grey literature. Due to study heterogeneity a meta-analysis was not possible and a narrative synthesis was performed.Results: 8,780 unique studies were identified and twenty-six included following a systematic search last updated in 2015. The majority of papers demonstrated substantial variability in the likelihood of receiving chemotherapy between hospitals, health authorities, cancer networks and UK countries (England and Wales). After case-mix adjustment, there was up to a 4-5 fold difference in chemotherapy utilisation between the highest and lowest prescribing cancer networks. There was no strong evidence that rurality or distance travelled were associated with the likelihood of receiving chemotherapy and conflicting evidence for an effect of travel time.Conclusions: Considerable variation in chemotherapy prescribing between healthcare boundaries has been identified. The absence of associations with natural geographical characteristics (e.g. rurality) and receipt of chemotherapy suggests that local treatment habits, capacity and policy are more influential. [ABSTRACT FROM AUTHOR]

Background: Anxiety is a common concern of cancer survivors during the transition from active cancer treatment to cancer survivorship (the re-entry phase). This paper presents the study protocol for a novel group-based behavioral intervention to improve mental health, well-being, and medical use outcomes among anxious cancer survivors at re-entry.Methods/design: This two-armed, prospective randomized controlled trial will randomize a minimum of 100 re-entry-phase cancer survivors with moderate to high anxiety to the intervention or a usual care control condition. The intervention is delivered in a group format over 7 weeks; content is based on Acceptance and Commitment Therapy (ACT), an acceptance, mindfulness, and values-based intervention. Participants will be recruited from community cancer care centers and the intervention will be led by the onsite clinical social workers. Participants will be assessed at baseline, mid-intervention, post-intervention, and 3- and 6-month follow-up. ACT participants will complete process measures before the beginning of group sessions 2, 4, and 6; all participants will complete the process measures during the regular assessments. The primary outcome is anxiety symptoms; secondary outcomes include anxiety disorder severity, fear of recurrence, depressive symptoms, cancer-related trauma symptoms, sense of life meaning, vitality/fatigue, and medical utilization.Discussion: This clinical trial will provide valuable evidence regarding the efficacy of the group ACT intervention in community oncology settings.Trial Registration: Clinicaltrials.gov NCT02550925 . [ABSTRACT FROM AUTHOR]

Background: Although previous studies have reported the efficacy of communication skills training (CST) programs, specific training addressing communication about uncertainty and hope in oncology has not yet been studied. This paper describes the study protocol of a randomized controlled trial assessing the efficacy of a CST program aimed at improving physician ability to communicate about uncertainty and hope in encounters with cancer patients.Methods/design: Physician participants will be randomly assigned in groups (n = 3/group) to a 30-h CST program (experimental group) or to a waiting list (control group). The training program will include learner-centered, skills-focused, practice-oriented techniques. Training efficacy is assessed in the context of an encounter with a simulated advanced stage cancer patient at baseline and after the CST for the experimental group, and after four months for the waiting-list group. Efficacy assessments will include communicational, psychological and physiological measures. Group-by-time effects will be analyzed using a generalized estimating equation (GEE). A power analysis indicated that a sample size of 60 (30 experimental and 30 control) participants will be sufficient to detect effects.Discussion: The current study will aid in the development of effective CST programs to improve physician ability to communicate about uncertainty and hope in encounters with cancer patients.Trial Registration: US Clinical Trials Register NCT02836197 . [ABSTRACT FROM AUTHOR]

Background: Head and neck cancer patients undergoing concomitant chemoradiotherapy (CCRT) frequently experience loss of muscle mass and reduced functional performance. Positive effects of exercise training are reported for many cancer types but biological mechanisms need further elucidation. This randomized study investigates whether progressive resistance training (PRT) may attenuate loss of muscle mass and functional performance. Furthermore, biochemical markers and muscle biopsies will be investigated trying to link biological mechanisms to training effects.Methods: At the Departments of Oncology at Herlev and Aarhus University Hospitals, patients with stage III/IV squamous cell carcinoma of the head and neck, scheduled for CCRT are randomized 1:1 to either a 12-week PRT program or control group, both with 1 year follow-up. Planned enrollment is 72 patients, and stratification variables are study site, sex, p16-status, and body mass index. Primary endpoint is difference in change in lean body mass (LBM) after 12 weeks of PRT, assessed by dual-energy X-ray absorptiometry (DXA). The hypothesis is that 12 weeks of PRT can attenuate the loss of LBM by at least 25%. Secondary endpoints include training adherence, changes in body composition, muscle strength, functional performance, weight, adverse events, dietary intake, self-reported physical activity, quality of life, labor market affiliation, blood biochemistry, plasma cytokine concentrations, NK-cell frequency in blood, sarcomeric protein content in muscles, as well as muscle fiber type and fiber size in muscle biopsies. Muscle biopsies are optional.Discussion: This randomized study investigates the impact of a 12-week progressive resistance training program on lean body mass and several other physiological endpoints, as well as impact on adverse events and quality of life. Furthermore, a translational approach is integrated with extensive biological sampling and exploration into cytokines and mechanisms involved. The current paper discusses decisions and methods behind exercise in head and neck cancer patients undergoing concomitant chemoradiotherapy.Trial Registration: Approved by the Regional Ethics Committee for the Capital Region of Denmark (protocol id: H-15003725) and registered retrospectively at ClinicalTrials.gov ( NCT02557529 ) September 11th 2015. [ABSTRACT FROM AUTHOR]

Background: This paper describes the multi-institutional prospective phase II clinical trial, SPARK: Stereotactic Prostate Adaptive Radiotherapy utilizing Kilovoltage Intrafraction Monitoring (KIM). KIM is a real-time image guided radiotherapy technology being developed and clinically pioneered for prostate cancer treatment in Australia. It has potential for widespread use for target radiotherapy treatment of cancers of the pelvis, thorax and abdomen.Methods: In the SPARK trial we will measure the cancer targeting accuracy and patient outcomes for 48 prostate cancer patients who will be treated in five treatment sessions as opposed to the conventional 40 sessions. The reduced number of treatment sessions is enabled by the KIM's increased cancer targeting accuracy.Discussion: Real-time imaging in radiotherapy has the potential to decrease the time taken during cancer treatment and reduce the imaging dose required. With the imaging being acquired during the treatment, and the analysis being automated, there is potential for improved throughput. The SPARK trial will be conducted under the auspices of the Trans-Tasman Radiation Oncology Group (TROG).Trial Registration: This trial was registered on ClinicalTrials.gov on 09 March 2015. The identifier is: NCT02397317. [ABSTRACT FROM AUTHOR]

Background: Clinical research has established the efficacy of exercise in reducing treatment-related side-effects and increasing wellbeing in people with cancer. Major oncology organisations have identified the importance of incorporating exercise in comprehensive cancer care but information regarding effective approaches to translating evidence into practice is lacking. This paper describes the implementation of a community-based exercise program for people with cancer and the protocol for program evaluation.Methods/design: The Life Now Exercise program is a community-based exercise intervention designed to mitigate and rehabilitate the adverse effects of cancer and its treatment and improve physical and psychosocial wellbeing in people with cancer. Involvement in the program is open to people with any diagnosis of cancer who are currently receiving treatment or within 2 years of completing treatment. The 3-month intervention consists of twice weekly group-based exercise sessions administered in community exercise clinics under the supervision of exercise physiologists trained to deliver the program. Evaluation of the program involves measures of uptake, safety, adherence and effectiveness (including cost effectiveness) as assessed at the completion of the program and 6 months follow-up.Discussion: To bridge the gap between research and practice, the Life Now Exercise program was designed and implemented to provide people with cancer access to evidence-based exercise medicine. The framework for program implementation and evaluation offers insight into the development of feasible, generalizable and sustainable supportive care services involving exercise. Community-based exercise programs specifically designed for people with cancer are necessary to facilitate adherence to international guidelines advising patients to participate in high-quality exercise.Trial Registration: ACTRN12616001669482 (retrospectively registered 5 Dec 2016). [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer survivors are not only at risk for recurrent disease but also at increased risk of comorbidities such as other cancers, cardiovascular disease, diabetes, hypertension and functional decline. In this trial, we aim at investigating whether a diet in accordance with the Norwegian food-based dietary guidelines and focusing at dampening inflammation and oxidative stress will improve long-term disease outcomes and survival in colorectal cancer patients.Methods/design: This paper presents the study protocol of the Norwegian Dietary Guidelines and Colorectal Cancer Survival study. Men and women aged 50-80 years diagnosed with primary invasive colorectal cancer (Stage I-III) are invited to this randomized controlled, parallel two-arm trial 2-9 months after curative surgery. The intervention group (n = 250) receives an intensive dietary intervention lasting for 12 months and a subsequent maintenance intervention for 14 years. The control group (n = 250) receives no dietary intervention other than standard clinical care. Both groups are offered equal general advice of physical activity. Patients are followed-up at 6 months and 1, 3, 5, 7, 10 and 15 years after baseline. The study center is located at the Department of Nutrition, University of Oslo, and patients are recruited from two hospitals within the South-Eastern Norway Regional Health Authority. Primary outcomes are disease-free survival and overall survival. Secondary outcomes are time to recurrence, cardiovascular disease-free survival, compliance to the dietary recommendations and the effects of the intervention on new comorbidities, intermediate biomarkers, nutrition status, physical activity, physical function and quality of life.Discussion: The current study is designed to gain a better understanding of the role of a healthy diet aimed at dampening inflammation and oxidative stress on long-term disease outcomes and survival in colorectal cancer patients. Since previous research on the role of diet for colorectal cancer survivors is limited, the study may be of great importance for this cancer population.Trial Registration: ClinicalTrials.gov Identifier: NCT01570010 . [ABSTRACT FROM AUTHOR]

Background: This paper describes about a study protocol of phase I/II multicenter prospective clinical trial evaluating the feasibility and efficacy of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced uterine cervical cancer patients.Methods and Design: Patients with histologically confirmed FIGO stage IB2, IIA2, IIB, and IIIB uterine cervical carcinoma width of which is larger than 5 cm assessed by MRI will be entered to this clinical trial. Protocol therapy is 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP (40 mg/m(2)), followed by 24 Gy in 4 fractions of HBT and central shield EBRT up to 50-50.4 Gy in 25-28 fractions. Tumor width is assessed again within one week before the first HBT and if the tumor width is larger than 4 cm, patients proceed to the secondary registration. In phase I section, feasibility of this will be investigated. If less than 10 % out of 20 patients experienced greater than grade 3 acute non-hematologic adverse effects, the study proceeds to phase II part. In phase II part a total of 55 patients will be accrued and the efficacy of the HBT will be investigated comparing with historical control data. If the lower margin of 90 % confidence interval of the 2-year pelvic progression-free survival of the HBT trial is higher than 64 %, the HBT is considered to be more effective than conventional ICBT.Discussion: The aim of this study is to demonstrate the feasibility and efficacy of the HBT for locally advanced cervical cancer. This trial will clarify the indication, feasibility, and efficacy of this new technique.Trial Registration: UMIN000019081 ; Registration date: 2015/9/30. [ABSTRACT FROM AUTHOR]

Background: Total laryngectomy with or without adjuvant (chemo)radiation often induces speech, swallowing and neck and shoulder problems. Speech, swallowing and shoulder exercises may prevent or diminish these problems. The aim of the present paper is to describe the study, which is designed to investigate the effectiveness and cost-utility of a guided self-help exercise program built into the application "In Tune without Cords" among patients treated with total laryngectomy.Methods/design: Patients, up to 5 years earlier treated with total laryngectomy with or without (chemo)radiation will be recruited for participation in this study. Patients willing to participate will be randomized to the intervention or control group (1:1). Patients in the intervention group will be provided access to a guided self-help exercise program and a self-care education program built into the application "In Tune without Cords". Patients in the control group will only be provided access to the self-care education program. The primary outcome is the difference in swallowing quality (SWAL-QOL) between the intervention and control group. Secondary outcome measures address speech problems (SHI), shoulder disability (SDQ), quality of life (EORTC QLQ-C30, QLQ-H&N35 and EQ-5D), direct and indirect costs (adjusted iMCQ and iPCQ measures) and self-management (PAM). Patients will be asked to complete these outcome measures at baseline, immediately after the intervention or control period (i.e. at 3 months follow-up) and at 6 months follow-up.Discussion: This randomized controlled trial will provide knowledge on the effectiveness of a guided self-help exercise program for patients treated with total laryngectomy. In addition, information on the value for money of such an exercise program will be provided. If this guided self-help program is (cost)effective for patients treated with total laryngectomy, the next step will be to implement this exercise program in current clinical practice.Trial Registration: NTR5255 Protocol version 4 date September 2015. [ABSTRACT FROM AUTHOR]

Background: Endocrine resistance is a major obstacle to optimal treatment effect in breast cancer. Some genetic markers have been proposed to predict response to aromatase inhibitors (AIs) but the data is insufficient. The aim of the study was to find new genetic treatment predictive markers of AIs.Methods: The ongoing population-based BC-blood study in Lund, Sweden includes women with primary breast cancer. This paper is based on AI-treated patients with estrogen receptor positive tumors who underwent breast cancer surgery in 2002-2008. First, an exploratory analysis of 1931 SNPs in 227 genes involved in absorption, distribution, metabolism, and elimination of multiple medications, using DMET™ chips, was conducted in a subset of the cohort with last follow-up in December 31st 2011 (13 cases, 11 controls). Second, selected SNPs from the first analysis were re-analyzed concerning risk for early breast cancer events in the extended cohort of 201 AI-treated with last follow-up in June 30th 2014. Clinical data were obtained from medical records and population registries.Results: Only CYP1A2 rs762551 C-allele was significantly associated with increased risk for early events in the 24 patients (P = 0.0007) and in the extended cohort, adjusted Hazard ratio (HR) 2.22 (95% CI 1.03-4.80). However, the main prognostic impact was found within five years, adjusted HR 7.88 (95% CI 2.13-29.19). The impact of the CYP1A2 rs762551 C-allele was modified by a functional polymorphism in the regulator gene AhR Arg554Lys (G > A). Compared to patients who were homozygous for the major allele in both genes (CYP1A2 A/A and AhR G/G), a 9-fold risk for early events was found in patients who had at least one minor allele in both genes, adjusted HR 8.95 (95% CI 2.55-31.35), whereas patients with at least one minor allele in either but not both genes had a 3-fold risk for early events, adjusted HR 2.81 (95% CI 1.07-7.33). The impact of CYP1A2 rs762551 C-allele was also modified by the CYP19A1 rs4646 C/C, adjusted HR 3.39 (95% CI 1.60-7.16) for this combination. This association was strongest within the first five years, adjusted HR 10.42 (95% CI 3.45-31.51).Conclusion: CYP1A2 rs762551 was identified as a new potential predictive marker for early breast cancer events in AI-treated breast cancer patients. Moreover, combined genotypes of CYP1A2 rs762551 and CYP19A1 rs4646 or AhR Arg554Lys could further improve prediction of early AI-treatment response. If confirmed, these results may provide a way to more personalized medicine. [ABSTRACT FROM AUTHOR]

Background: Obesity is associated with tumor aggressiveness and disease-specific mortality for more than 15 defined malignancies, including prostate cancer. Preclinical studies suggest that weight loss from caloric restriction and increased physical activity may suppress hormonal, energy-sensing, and inflammatory factors that drive neoplastic progression; however, exact mechanisms are yet to be determined, and experiments in humans are limited.Methods: We conducted a randomized controlled trial among 40 overweight or obese, newly-diagnosed prostate cancer patients who elected prostatectomy to explore feasibility of a presurgical weight loss intervention that promoted a weight loss of roughly one kg. week(-1) via caloric restriction and physical activity, as well as to assess effects on tumor biology and circulating biomarkers. Measures of feasibility (accrual, retention, adherence, and safety) were primary endpoints. Exploratory aims were directed at the intervention's effect on tumor proliferation (Ki-67) and other tumor markers (activated caspase-3, insulin and androgen receptors, VEGF, TNFβ, NFκB, and 4E-BP1), circulating biomarkers (PSA, insulin, glucose, VEGF, TNFβ, leptin, SHBG, and testosterone), lymphocytic gene expression of corresponding factors and cellular bioenergetics in neutrophils, and effects on the gut microbiome. Consenting patients were randomized in a 1:1 ratio to either: 1) weight loss via a healthful, guidelines-based diet and exercise regimen; or 2) a wait-list control. While biological testing is currently ongoing, this paper details our methods and feasibility outcomes.Results: The accrual target was met after screening 101 cases (enrollment rate: 39.6%). Other outcomes included a retention rate of 85%, excellent adherence (95%), and no serious reported adverse events. No significant differences by age, race, or weight status were noted between enrollees vs. non-enrollees. The most common reasons for non-participation were "too busy" (30%), medical exclusions (21%), and "distance" (16%).Conclusions: Presurgical trials offer a means to study the impact of diet and exercise interventions directly on tumor tissue, and other host factors that are feasible and safe, though modifications are needed to conduct trials within an abbreviated period of time and via distance medicine-based approaches. Pre-surgical trials are critical to elucidate the impact of lifestyle interventions on specific mechanisms that mediate carcinogenesis and which can be used subsequently as therapeutic targets.Trial Registration: NCT01886677. [ABSTRACT FROM AUTHOR]

Background: Patients with acute leukemia experience a substantial symptom burden and are at risk of developing infections throughout the course of repeated cycles of intensive chemotherapy. Physical activity in recent years has been a strategy for rehabilitation in cancer patients to remedy disease and treatment related symptoms and side effects. To date, there are no clinical practice exercise guidelines for patients with acute leukemia undergoing induction and consolidation chemotherapy. A randomized controlled trial is needed to determine if patients with acute leukemia can benefit by a structured and supervised counseling and exercise program.Methods/design: This paper presents the study protocol: Patient Activation through Counseling and Exercise--Acute Leukemia (PACE-AL) trial, a two center, randomized controlled trial of 70 patients with acute leukemia (35 patients/study arm) following induction chemotherapy in the outpatient setting. Eligible patients will be randomized to usual care or to the 12 week exercise and counseling program. The intervention includes 3 hours + 30 minutes per week of supervised and structured aerobic training (moderate to high intensity 70-80%) on an ergometer cycle, strength exercises using hand weights and relaxation exercise. Individual health counseling sessions include a self directed home walk program with a step counter. The primary endpoint is functional performance/exercise capacity (6 minute walk distance). The secondary endpoints are submaximal VO₂ max test, sit to stand and bicep curl test, physical activity levels, patient reported outcomes (quality of life, anxiety and depression, symptom prevalence, intensity and interference). Evaluation of clinical outcomes will be explored including incidence of infection, hospitalization days, body mass index, time to recurrence and survival. Qualitative exploration of patients' health behavior and experiences.Discussion: PACE-AL will provide evidence of the effect of exercise and health promotion counseling on functional and physical capacity, the symptom burden and quality of life in patients with acute leukemia during out patient management. The results will inform clinical practice exercise guidelines and rehabilitation programs for patients undergoing treatment for acute leukemia. Optimizing the treatment and care pathway may ease the transition for patients from illness to the resumption of everyday activities.Trial Registration: ClinicalTrials.gov Identifier: NCT01404520. [ABSTRACT FROM AUTHOR]

Background: Lymphatic vessel density and lymphovascular invasion are commonly assessed to identify the clinicopathological outcomes in breast cancer. However, the prognostic values of them on patients' survival are still uncertain.Methods: Databases of PubMed, Embase, and Web of Science were searched from inception up to 30 June 2016. The hazard ratio with its 95% confidence interval was used to determine the prognostic effects of lymphatic vessel density and lymphovascular invasion on disease-free survival and overall survival in breast cancer.Results: Nineteen studies, involving 4215 participants, were included in this study. With the combination of the results of lymphatic vessel density, the pooled hazard ratios and 95% confidence intervals were 2.02 (1.69-2.40) for disease-free survival and 2.88 (2.07-4.01) for overall survival, respectively. For lymphovascular invasion study, the pooled hazard ratios and 95% confidence intervals were 1.81 (1.57-2.08) for disease-free survival and 1.64 (1.43-1.87) for overall survival, respectively. In addition, 29.56% (827/2798) of participants presented with lymphovascular invasion in total.Conclusions: Our study demonstrates that lymphatic vessel density and lymphovascular invasion can predict poor prognosis in breast cancer. Standardized assessments of lymphatic vessel density and lymphovascular invasion are needed. [ABSTRACT FROM AUTHOR]

Background: Preoperative chemoradiotherapy (CRT) with CROSS regimen has been the recommended treatment for locally advanced esophageal squamous cell carcinoma (ESCC). The addition of programmed cell death protein 1 (PD-1) inhibitor to preoperative CRT may further improve oncologic results. Preoperative camrelizumab plus chemotherapy has been demonstrated as a promising treatment modality based on results of the phase II NICE study (ChiCTR1900026240).Methods: The NICE-2 study is designed as a three-arm, multicenter, prospective, randomized, phase II clinical trial, comparing camrelizumab plus chemotherapy (IO-CT) and camrelizumab plus CRT (IO-CRT) versus CRT as preoperative treatment for locally advanced ESCC. A total of 204 patients will be recruited from 8 Chinese institutions within 1.5 years. The primary endpoint is pathological complete response (pCR) rate and secondary endpoints include event-free survival (EFS), R0 resection rate, and adverse events.Discussion: This is the first prospective randomized controlled trial to explore commonly used neoadjuvant treatments in clinical practice, which will provide high-level evidence of neoadjuvant treatment for patients with locally advanced ESCC. The purpose of this study is to establish the optimal modality of IO-CT, IO-CRT and CRT as preoperative treatment for locally advanced ESCC. The Institution Review Committee approved this study protocol in August 2021 and patient enrollment was started in September 2021.Trial Registration: ClinicalTrial.gov: NCT05043688 (August 29, 2021). The trial was prospectively registered. [ABSTRACT FROM AUTHOR]

Background: Acquired resistance to approved tyrosine kinase inhibitors limits their clinical use in patients with gastrointestinal stromal tumor (GIST). This study investigated the safety, tolerability and efficacy of alpelisib, a phosphatidylinositol 3-kinase inhibitor, used in combination with imatinib in patients with advanced GIST who had failed prior therapy with both imatinib and sunitinib.Methods: This phase 1b, multicenter, open-label study consisted of 2 phases: dose escalation and dose expansion. Dose escalation involved 200 mg once daily (QD) alpelisib, initially, followed by 250 and 350 mg. These were combined with 400 mg QD imatinib until maximum tolerated dose (MTD) and/or a recommended phase 2 dose (RP2D) of alpelisib in combination with imatinib was determined. This MTD/RP2D dose was tested to evaluate the clinical activity of this combination in dose expansion.Results: Fifty-six patients were enrolled, 21 and 35 in the dose escalation and expansion phases, respectively. The MTD of alpelisib given with imatinib was determined as 350 mg QD. Combination treatment showed partial response in 1 (2.9%) and stable disease in 15 (42.9%) patients. Median progression-free survival was 2 months (95% CI 1.8-4.6). Overall, 92.9% patients had adverse events (AEs) while 46.4% had grade 3/4 AEs, hyperglycemia being the most common (23.2%).Conclusions: The MTD of alpelisib was estimated as 350 mg QD when used in combination with imatinib 400 mg QD after oral administration in patients with advanced GIST. The safety and tolerability profile of this combination was acceptable; however, the combination did not demonstrate sufficient clinical activity to justify additional clinical testing.Trial Registration: ClinicalTrials.gov NCT01735968 (date of initial registration 28/11/2012). [ABSTRACT FROM AUTHOR]

Combination chemoimmunotherapy (CIT) consisting of anti-CD20 has improved the progression-free survival (PFS) and overall survival (OS) of patients with chronic lymphocytic leukaemia (CLL). We performed a comprehensive synthesis of prognostic factors in patients with CLL on combined CIT with anti-CD20 antibodies compared with standard chemotherapy alone or targeted therapy.We searched the MEDLINE and academic search complete electronic databases as well as clinicaltrials.gov (from inception up to 01 August 2022) for randomised controlled trials examining chemoimmunotherapy and targeted therapy in patients with CLL. The risk of bias and the quality of evidence was assessed using the quality in prognostic studies tool (QUIPS).A total of 10 prognostic factors were identified and evaluated in patients with CLL on anti-CD20 antibody-containing CIT. The predictive value of the following prognostic factors was confirmed and associated with poor patient outcomes; deletion 17p (HR = 3.39), Immunoglobulin heavy chain variable region gene mutation status (HR = 0.96) and β2-microglobulin (HR = 1.41).Conventional predictive factors may have retained prognostic value and could be useful in the stratification of patients who may be non-responsive to CIT.Trial registration: International Prospective Register of Systematic Reviews (PROSPERO) registry (CRD42021218997). [ABSTRACT FROM AUTHOR]

Background: Nutritional support, including nutritional counseling and oral nutritional supplements (ONS), has been recommended as a first-line strategy in patients with non-small cell lung cancer (NSCLC). Evidence on the efficacy of immunonutrition during immunotherapy in these patients is positive, but still limited some secondary endpoints, such as treatment toxicity and tolerance. We hypothesize that early systematic provision of ONS with a high-protein-high calorie mixture containing immunonutrients (Impact®) in addition to nutritional counseling, compared to nutritional counseling alone, is beneficial to patients with NSCLC receiving immunotherapy with or without chemotherapy. We designed the present study to evaluate the efficacy of early systematic provision of ONS enriched with immunonutrients compared to nutritional counseling alone, in patients with NSCLC undergoing immunotherapy. Study endpoints were: treatment response (primary endpoint: progression-free survival), treatment tolerance and toxicity, body weight, body composition, protein-calorie intake, quality of life, fatigue, muscle strength and immunological profile.Methods: This is a pragmatic, multicentre, randomized (1:1), parallel-group, open label, controlled, pilot clinical trial (N = 180).Discussion: The improvement of efficacy of nutritional support in oncology still deserves many efforts. Immunonutrition represents a promising approach also in patients with NSCLC, but evidence on its efficacy on clinical outcomes during immunotherapy is still inconclusive. The present pilot study, which guarantees early high-quality nutritional care (assessment and treatment) to all patients in agreement with current guidelines and recommendations, could represent one of the first proofs of efficacy of early oral immunonutrition in patients with cancer undergoing immunotherapy. Further large randomized trials addressing the improvement of supportive care could be hypothesized, accordingly.Trial Registration: This study is registered on ClinicalTrials.gov Identifier: NCT05384873. [ABSTRACT FROM AUTHOR]

Background: For patients with acute myeloid leukaemia (AML), the only potentially curative treatment is intensive chemotherapy (IC). This is highly toxic, particularly for patients > 60 years, potentially leading to prolonged hospitalisations requiring intensive supportive care, and sometimes treatment-related death. This also results in extensive healthcare costs and negatively impacts quality of life (QoL). Venetoclax with low-dose cytarabine (VEN + LDAC) is a novel, low-intensity treatment for AML patients who cannot receive IC. VEN + LDAC is given as an outpatient and toxicity appears significantly lower than with IC. Analysis of clinical trials performed to date are promising for patients with the genotype NPM1mutFLT3 ITDneg, where remission and survival rates appear comparable to those achieved with IC.Methods: VICTOR is an international, two-arm, open-label, multi-centre, non-inferiority, randomised-controlled phase II trial to assess VEN + LDAC compared to standard of care (IC) as first-line treatment in older patients (initially aged ≥ 60 years) with newly diagnosed AML. The trial will recruit patients with a NPM1mutFLT3 ITDneg genotype; those with a favourable risk in relation to the experimental treatment. University of Birmingham is the UK co-ordinating centre, with national hubs in Aarhus University Hospital, Denmark, and Auckland District Health Board, New Zealand. The primary outcome is molecular event-free survival time where an event is defined as failure to achieve morphological complete response (CR) or CR with incomplete blood count recovery after two cycles of therapy; molecular persistence, progression or relapse requiring treatment change; morphological relapse, or; death. Secondary outcomes include cumulative resource use at 12- and 24-months, and QoL as assessed by EORTCQLQ-C30 and EQ-5D-3L at 3-, 6-, 12-, 18- and 24-months. The trial employs an innovative Bayesian design with target sample size of 156 patients aged > 60 years.Discussion: The principle underpinning the VICTOR trial is that the chance of cure for patients in the experimental arm should not be compromised, therefore, an adaptive design with regular checks on accumulating data has been employed, which will allow for a staged expansion of the trial population to include younger patients if, and when, there is sufficient evidence of non-inferiority in older patients.Trial Registration: EudraCT: 2020-000,273-24; 21-Aug-2020.Isrctn: 15,567,173; 08-Dec-2020. [ABSTRACT FROM AUTHOR]

Background: Lynch Syndrome (LS) is an inherited cancer predisposition syndrome defined by pathogenic variants in the mismatch repair (MMR) or EPCAM genes. In the United Kingdom, people with LS are advised to undergo biennial colonoscopy from as early as 25 until 75 years of age to mitigate a high lifetime colorectal cancer (CRC) risk, though the consideration of additional surveillance intervention(s) through the application of non-invasive diagnostic devices has yet to be longitudinally observed in LS patients. In this study, we will examine the role of annual faecal immunochemical testing (FIT) alongside biennial colonoscopy for CRC surveillance in people with LS.Methods/design: In this single-arm, prospective, non-randomised study, 400 LS patients will be recruited across 11 National Health Service (NHS) Trusts throughout the United Kingdom. Study inclusion requires a LS diagnosis, between 25 and 73 years old, and a routine surveillance colonoscopy scheduled during the recruitment period. Eligible patients will receive a baseline OC-Sensor™ FIT kit ahead of their colonoscopy, and annually for 3 years thereafter. A pre-paid envelope addressed to the central lab will be included within all patient mailings for the return of FIT kits and relevant study documents. A questionnaire assessing attitudes and perception of FIT will also be included at baseline. All study samples received by the central lab will be assayed on an OC-Sensor™ PLEDIA Analyser. Patients with FIT results of ≥6 μg of Haemoglobin per gram of faeces (f-Hb) at Years 1 and/or 3 will be referred for colonoscopy via an urgent colonoscopy triage pathway. 16S rRNA gene V4 amplicon sequencing will be carried out on residual faecal DNA of eligible archived FIT samples to characterise the faecal microbiome.Discussion: FIT may have clinical utility alongside colonoscopic surveillance in people with LS. We have designed a longitudinal study to examine the efficacy of FIT as a non-invasive modality. Potential limitations of this method will be assessed, including false negative or false positive FIT results related to specific morphological features of LS neoplasia or the presence of post-resection anastomotic inflammation. The potential for additional colonoscopies in a subset of participants may also impact on colonoscopic resources and patient acceptability.Trial Registration: Trial Registration: ISRCTN, ISRCTN15740250 . Registered 13 July 2021. [ABSTRACT FROM AUTHOR]

Introduction: Radiation therapy is one of the standard methods in the treatment of breast cancer. Radiotherapy-induced dermatitis (RID) is a common complication of radiotherapy (RT) resulting in less tolerance in RT and even discontinuation of treatment. Timolol is a β-adrenergic receptor antagonist that presents the best wound healing effects on both chronic and incurable wound healing. Topical forms of timolol could be effective in the prevention of RID due to the role of β-adrenergic receptors in skin cells and keratinocyte migration, as well as the anti-inflammatory effect of timolol. However, no placebo-controlled randomized trial is available to confirm its role. The current trial aimed to evaluate the efficacy of topical timolol 0.5% (w/w) on the RID severity and patients' quality of life (QOL).Method: Patients aged older than 18 years with positive histology confirmed the diagnosis of invasive and localized breast cancer were included. Patients were randomized based on the random number table to receive each of the interventions of timolol 0.5% (w/w) or placebo topical gels from the first day of initiation of RT and for 6 weeks, a thin layer of gel twice daily. Patients were asked to use a thin layer of gel for at least two hours before and after radiation therapy. Primary outcomes were acute radiation dermatitis (ARD) grade using Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer (RTOG/EORTC) scale and severity of desquamation based on Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Secondary outcomes were QOL based on Skindex16 (SD-16), maximum grade of ARD, and time of initial RD occurrence.Results: A total of 64 female patients with an age range of 33 to 79 years were included. The means (SD) of age were 53.88 (11.02) and 54.88 (12.48) in the control and timolol groups, respectively. Considering the RTOG/EORTC and CTCAE scores the difference between groups was insignificant (P-Value = 0.182 and P-Value = 0.182, respectively). In addition, the mean (SD) of time of initial RID occurrence in placebo and timolol groups were 4.09 (0.588) and 4.53 (0.983) weeks, respectively (P-Value = 0.035). The maximum grade of RID over time was significantly lower in the timolol group. During the study period, 75.0% of patients in placebo groups had grade 2 of ARD while in the timolol group it was 31.3% (P-Value = 0.002). QoL was not significantly different between groups (P-Value = 0.148).Conclusion: Although the topical formulation of timolol, 0.5% (w/w), was found to reduce the average maximum grade of ARD and increase the mean (SD) time of initial RID occurrence, it showed no effect on ARD, severity, and QOL. However, future clinical trials should be performed to assess timolol gel formulation in larger study populations.Trial Registration: https://irct.ir/ IRCT20190810044500N11 (17/03/2021). [ABSTRACT FROM AUTHOR]

Background: Cancer is a frightening disease. Therefore, the care of cancer patients is very complex. This study aimed to investigate the effect of the education based on Orem's self-care model on self-care abilities of the patients undergoing chemotherapy in Shafa Hospital in Ahvaz city, Iran.Methods: This randomized clinical trial was carried out in 2018 on 100 cancer patients undergoing chemotherapy, who referred to Shafa Hospital in Ahvaz city, Iran. The sampling method was simple and the subjects were randomly divided into two experimental and control groups (50 in the experimental and 50 in the control group). The study outcome was the self-care ability of the patients measured before and 2 months after the intervention by the control and experimental groups. The educational intervention consisted of five 60-minute sessions (one session per week) held as educational and counseling ones through group, face-to-face and individual training based on the identified needs of the patients in the experimental group at Shafa Hospital Chemotherapy Department. To collect data, two questionnaires [the assess and identify the conceptual pattern of Orem questionnaire and the Self-care capacity assessment (ESCI)]were used. Statistical data were entered into SPSS software version 20 and analyzed by chi-square, independent t-test and paired t-test.Results: The mean and standard deviation of age was 35.06 ± 14.51 in the control group and 31.72 ± 15.01 in the experimental group. The results of the independent t-test showed that before the educational intervention, there was no significant difference between the two groups in terms of the mean self-care (P = 0.38). But after the intervention, a significant difference was found between the mean self-care scores of the experimental and control groups (P = 0.001).Conclusion: Application of Orem's self-care model led to increased self-care ability of the cancer patients undergoing chemotherapy. Therefore, it is recommended that this model be included in the routine programs of chemotherapy departments.Trial Registration: IRCT registration number: IRCT20160418027449N6. Registration date: 01/05/2019. [ABSTRACT FROM AUTHOR]

Background: Pomalidomide in combination with dexamethasone has demonstrated positive results in patients with relapsed or refractory multiple myeloma (RRMM), but no data are available in China. We conducted a multicenter, single-arm trial to examine the efficacy and safety of bioequivalent generic pomalidomide plus low-dose dexamethasone in Chinese RRMM patients.Methods: Adult (≥ 18 years of age) RRMM patients who progressed after at least two previous treatments, including bortezomib and lenalidomide, were eligible. Pomalidomide was given orally at 4 mg/day on days 1 to 21 of a 28-day cycle. Dexamethasone was given at 40 mg/day (either orally or intravenously; 20 mg/day at 75 years or older) on days 1, 8, 15, and 22 of each cycle. Treatment continued until disease progression or intolerable adverse events (AEs). The primary end point was objective response rate (ORR).Results: Seventy-four patients were enrolled between February 2017 and February 2019. All patients had progressed within 60 days of their last therapy. 74.3% of the patients were resistant to lenalidomide, 31.1% had renal insufficiency and 33.8% had high-risk cytogenetic RRMM. The median follow-up duration was 33.0 months (range 31.1-34.8 months). The ORR was 37.8% in the overall analysis, 32.7% in lenalidomide-refractory patients, 36.0% in patients with high-risk cytogenetics and 34.8% in RRMM patients with renal impairment. The median progression-free survival was 5.7 months (95% CI 3.7-8.8 months). The median overall survival was 24.3 months (95% CI 14.4-41.1 months). The most common grade 3 and 4 treatment-emergent adverse events (TEAEs) were neutropenia (63.5%), leukopenia (37.8%), thrombocytopenia (28.4%), and anemia (31.1%). Pulmonary infection (27.0%) was the most frequent grade 3 and 4 nonhematologic TEAE. No previously unreported AEs were observed. No venous thromboembolism was reported.Conclusions: Pomalidomide in combination with low-dose dexamethasone is effective and safe in Chinese RRMM patients.Trial Registration: The study is registered at Chinese Clinical Trial Registry (ChiCTR) ( ChiCTR-OIC-17013234 , first registered on 03/11/2017). [ABSTRACT FROM AUTHOR]

Background: The C-X-C chemokine receptor 4 (CXCR4) has been suggested to play an important role in several types of cancers and is related to biological behaviors connected with tumor progression. However, the clinical significance and application of CXCR4 in lung cancer remain disputable. Thus, we conducted a meta-analysis to investigate the impact of CXCR4 expression on survival and clinicopathological features in lung cancer.Methods: Comprehensive literature searches were conducted in PubMed, Embase and Web of Science for relevant studies. We pooled hazard ratios (HRs)/odds ratios (ORs) with 95% confidence intervals (CIs) by STATA 12.0 to evaluate the potential value of CXCR4 expression.Results: Twenty-seven relevant articles involving 2932 patients with lung cancer were included in our meta-analysis. The results revealed that CXCR4 expression was apparently associated with poor overall survival (OS) (HR 1.61, 95% CI 1.42-1.82) and disease-free survival (HR 3.39, 95% CI 2.38-4.83). Furthermore, a significant correlation with poor OS was obvious in non-small cell lung cancer patients (HR 1.59, 95% CI 1.40-1.81) and in patients showing CXCR4 expression in the cytoplasm (HR 2.10, 95% CI 1.55-2.84) and the membrane (HR 1.74, 95% CI 1.24-2.45). CXCR4 expression was significantly associated with men (OR 1.32, 95% CI 1.08-1.61), advanced tumor stages (T3-T4) (OR 2.34, 95% CI 1.28-4.28), advanced nodal stages (N > 0) (OR 2.34, 95% CI 1.90-2.90), distant metastasis (OR 3.65, 95% CI 1.53-8.69), advanced TNM stages (TNM stages III, IV) (OR 3.10, 95% CI 1.95-4.93) and epidermal growth factor receptor (EGFR) expression (OR 2.44, 95% CI 1.44-4.12) but was not associated with age, smoking history, histopathology, differentiation, lymphatic vessel invasion or local recurrence.Conclusion: High expression of CXCR4 is related to tumor progression and might be an adverse prognostic factor for lung cancer. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether the presence of human papillomavirus (HPV) DNA and p16 might be associated with better prognosis in patients with hypopharyngeal carcinoma (HPC), especially on overall survival (OS) and disease-free survival (DFS).Method: PubMed, the Cochrane Library, the Web of Science and EMBASE were searched from inception to April 2021 to search for HPV DNA- and p16-related prognostic articles on HPC. Meta-analysis was performed on the selected articles according to the inclusion and exclusion criteria. Publication bias was assessed for the included studies with Egger's test. All studies were analyzed by using Stata 16.0 statistical software.Results: A total of 18 studies were included, including 12 HPV DNA studies and 11 p16 studies. Meta-analysis showed that HPV DNA positivity was a strong prognostic factor for improved OS in patients with HPC, with a pooled hazard ratio (HR) of 0.61 (95% CI, 0.54-0.69), but there was no statistically significant difference in DFS (HR, 0.60; 95% CI, 0.31-1.16). Patients with p16-positive tumors had better OS (HR, 0.66; 95% CI, 0.49-0.89) and DFS (HR, 0.59; 95% CI, 0.44-0.78) than patients with p16-negative tumors.Conclusions: This study suggests that the presence of HPV DNA leads to better OS in patients with HPC, and the presence of p16 also corresponds to better OS and DFS. Our results provide up-to-date evidence to clinicians and researchers. Larger studies adjusting for prognostic factors are needed in subsequent studies. [ABSTRACT FROM AUTHOR]

Purpose: Given the psychosocial burdens patients in advanced stages of cancer face, innovative care concepts are needed. At the same time, such vulnerable patient groups are difficult to reach for participation in intervention studies and randomized patient inclusion may not be feasible. This article aims to identify systematic biases respectively selection effects occurring during the recruitment phase and to discuss their potential causes based on a non-randomized, multicenter intervention study with patients in advanced stages of cancer.Methods: Patients diagnosed with at least one of 16 predefined cancers were recruited at four hospitals in three German cities. The effect of social care nurses' continuous involvement in acute oncology wards was measured by health-related quality of life (EORTC QLQ-C30), information and participation preferences, decisional conflicts, doctor-patient communication, health literacy and symptom perception. Absolute standardized mean difference was calculated as a standardized effect size to test baseline characteristics balance between the intervention and control groups.Results: The study enrolled 362 patients, 150 in the intervention and 212 in the control group. Except for gender, both groups differed in relevant socio-demographic characteristics, e.g. regarding age and educational background. With respect to the distribution of diagnoses, the intervention group showed a higher symptom burden than the control group. Moreover, the control group reported better quality of life at baseline compared to the intervention group (52.6 points (SD 21.7); 47.8 points (SD 22.0), ASMD = 0.218, p = 0.044).Conclusion: Overall, the intervention group showed more social and health vulnerability than the control group. Among other factors, the wide range of diagnoses included and structural variation between the recruiting clinics increased the risk for bias. We recommend a close, continuous monitoring of relevant social and health-related characteristics during the recruitment phase as well as the use of appropriate statistical analysis strategies for adjustment, such as propensity score methods.Trial Registration: German Clinical Trials Register (DRKS-ID: DRKS00013640 ); registered on 29th December 2017. [ABSTRACT FROM AUTHOR]

Background: Bronchoscopy can be a distress for the patient. There have been few studies on the combination of sedatives and opioids. The aim of this study was to demonstrate the usefulness and safety of administration of the combination of midazolam and pethidine during bronchoscopy.Methods: In this prospective randomized single (patient)-blind study, we randomly assigned 100 patients who were scheduled to undergo bronchoscopy biopsy to receive treatment with either the midazolam/pethidine combination (combination group) or midazolam alone (midazolam group) during examinations. After the end of bronchoscopy, patients completed a questionnaire and the visual analogue scale was measured. The primary outcome was the patients' acceptance of re-examination assessed by visual analogue scale. We also assessed pain levels, vital signs, midazolam use, xylocaine use, and adverse events. Univariate analyses were performed using Fisher's exact test for categorical data, and the t-test or Mann-Whitney test was carried out for analysis of numeric data. All P-values were two-sided, and values < 0.05 were considered statistically significant.Results: We analyzed 47 patients in the combination group and 49 patients in the midazolam group. The primary outcome was a good trend in the combination group, but not significantly different (3.82 ± 2.3 in combination group versus 4.17 ± 2.75 in midazolam alone, P = 0.400). In the combination group, the visual analog scale score for pain during bronchoscopy was significantly lower (1.10 ± 1.88 versus 2.13 ± 2.42, P = 0.022), and the sedation level score per the modified observer's assessment of alertness/sedation scale was significantly deeper (3.49 ± 0.98 versus 3.94 ± 1.03, P = 0.031). Maximal systolic blood pressure during testing was significantly lower (162.39 ± 23.45 mmHg versus 178.24 ± 30.24 mmHg, P = 0.005), and the number of additional administrations of midazolam was significantly lower (2.06 ± 1.45 versus 2.63 ± 1.35, P = 0.049). There were also significantly fewer adverse events (30 versus 41, P = 0.036).Conclusions: The combination uses of midazolam and pethidine for sedation resulted in significant improvements in the pain, blood pressure, additional use of midazolam, and safety during bronchoscopy among patients.Trial Registration: This study was registered in the University Medical Hospital Information Network in Japan (UMINCTR Registration number: UMIN000032230 , Registered: 13/April/2018). [ABSTRACT FROM AUTHOR]

Objective: To present a systematic review of the literature and a meta-analysis evaluating the oncological safety of autologous fat grafting (AFG).Summary Background Data: AFG for breast reconstruction presents difficulties during follow-up radiological exams, and the oncological potential of grafted fat is uncertain. Previous studies confirmed that the fatty tissue could be transferred under a good condition suitable would not interfere with mammographic follow-up, although the issue of oncological safety remains.Methods: We reviewed the literature published until 01/18/2021. The outcomes were overall survival (OS), disease-free survival (DFS), and local recurrence (LR). We included studies that evaluated women with breast cancer who undergone surgery followed by reconstruction with AFG. We synthesized data using the inverse variance method on the log-HR (log of the hazard ratio) scale for time-to-event outcomes using RevMan. We assessed heterogeneity using the Chi2 and I2 statistics.Results: Fifteen studies evaluating 8541 participants were included. The hazard ratios (HR) could be extracted from four studies, and there was no difference in OS between the AFG group and control (HR 0.9, 95% CI 0.53 to 1.54, p = 0.71, I2 = 58%, moderate certainty evidence), and publication bias was not detected. The HR for DFS could be extracted from six studies, and there was no difference between the AFG group and control (HR 1.01, 95% CI 0.73 to 1.38, p = 0.96, I2 = 0%, moderate certainty evidence). The HR for LR could be extracted from ten studies, and there was no difference between the AFG group and control (HR 0.86, 95% CI 0.66 to 1.12, p = 0.43, I2 = 1%, moderate certainty evidence).Conclusion: According to the current evidence, AFG is a safe technique of breast reconstruction for patients that have undergone BC surgery and did not affect OS, DFS, or LR. [ABSTRACT FROM AUTHOR]

Objective: We aimed to evaluate the prognosis and adjuvant chemotherapy (ACT) in intrahepatic cholangiocarcinoma (ICC) patients with different etiology after radical resection.Methods: A total of 448 patients with ICC who underwent radical resection between 2010 and 2018 at ten Chinese tertiary hospitals were analyzed in the study. These patients were divided into conventional ICC (Con-ICC, n = 261, 58.2%), hepatitis B virus ICC (HBV-ICC, n = 102, 22.8%) and hepatolithiasis (Stone-ICC, n = 85,19.0%) subtypes according to different etiology. Propensity score matching (PSM) was conducted to mitigate the baseline differences between Con-ICC and HBV-ICC, Con-ICC and Stone-ICC, HBV-ICC and Stone-ICC subtypes.Results: Univariate and multivariate analysis showed that different etiology was a prognostic factor for overall survival and relapse-free survival, and different etiology was an independent risk factor for overall survival in ICC patients, respectively (P < 0.05). In addition, there was a statistical difference for overall survival in early recurrence patients among the three etiological subtypes (P < 0.05). After PSM, the overall survival of patients with Stone-ICC was worse than those of Con-ICC and HBV-ICC subtypes (P < 0.05), while the relapse-free survival of patients with Stone-ICC was equivalent to patients with Con-ICC and HBV-ICC (P > 0.05). In Stone-ICC patients, the median overall survival was 16.0 months and 29.7 months, and the median relapse-free survival was 9.0 months and 20.0 months for non-ACT and ACT patients, respectively (P < 0.05).Conclusion: The prognosis of Stone-ICC patients was significantly worse than those of Con-ICC and HBV-ICC patients. Interestingly, postoperative adjuvant chemotherapy can improve the prognosis of Stone-ICC patients effectively. [ABSTRACT FROM AUTHOR]

Background: Lower limb lymphedema (LLL) is one of the most refractory and debilitating complications related to gynecological cancer treatment. We investigated factors associated with response to compression-based physical therapy (CPT) for secondary LLL after gynecologic cancer treatment.Methods: We performed a multicenter retrospective study using the records of seven medical institutions from 2002 and 2014. Patients who developed LLL after gynecological cancer treatment were included. Limb volumes were calculated from the lengths of the limb circumferences at four points. All participants underwent compression-based physical therapy for LLL. Factors, including MLD, indicative of circumference reductions in LLL were determined.Results: In total, 1,034 LLL met the required criteria of for the study. A multivariate linear regression analysis identified age; body mass index (BMI); endometrial cancer; radiotherapy; and initial limb circumference as significant independent prognostic factors related to improvement in LLL. In analysis of covariance for improvement in LLL adjusted by the initial limb circumference and stratified by BMI and radiotherapy, patients with BMI 28 kg/m2 or higher and receiving radiation rarely responded to CPT.Conclusions: Improvements in the lower limb circumference correlated with clinical histories and physical characteristics, which may be used as independent prognostic factors for successful CPT for LLL after gynecological cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Medicinal plant is a main source of cancer drug development. Some of the cycloartane triterpenoids isolated from the aerial part of Cimicifuga dahurica showed cytotoxicity in several cancer cell lines. It is of great interest to examine the antiproliferative activity and mechanisms of total triterpenoid glycosides of C. dahurica and therefore might eventually be useful in the prevention or treatment of Hepatoma.Methods: The total glycosides from the aerial part (TGA) was extracted and its cytotoxicity was evaluated in HepG2 cells and primary cultured normal mouse hepatocytes by an MTT assay. Morphology observation, Annexin V-FITC/PI staining, cell cycle analysis and western blot were used to further elucidate the cytotoxic mechanism of TGA. Implanted mouse H22 hepatoma model was used to demonstrate the tumor growth inhibitory activity of TGA in vivo.Results: The IC50 values of TGA in HepG2 and primary cultured normal mouse hepatocytes were 21 and 105 mug/ml, respectively. TGA induced G0/G1 cell cycle arrest at lower concentration (25 mug/ml), and triggered G2/M arrest and apoptosis at higher concentrations (50 and 100 mug/ml respectively). An increase in the ratio of Bax/Bcl-2 was implicated in TGA-induced apoptosis. In addition, TGA inhibited the growth of the implanted mouse H22 tumor in a dose-dependent manner.Conclusion: TGA may potentially find use as a new therapy for the treatment of hepatoma. [ABSTRACT FROM AUTHOR]

Background: At present, hepatectomy is still the most common and effective treatment method for intrahepatic cholangiocarcinoma (ICC) patients. However, the postoperative prognosis is poor. Therefore, the prognostic factors for these patients require further exploration. Whether microvascular invasion (MVI) plays a crucial role in the prognosis of ICC patients is still unclear. Moreover, few studies have focused on preoperative predictions of MVI in ICC patients.Methods: Clinicopathological data of 704 ICC patients after curative resection were retrospectively collected from 13 hospitals. Independent risk factors were identified by the Cox or logistic proportional hazards model. In addition, the survival curves of the MVI-positive and MVI-negative groups before and after matching were analyzed. Subsequently, 341 patients from a single center (Eastern Hepatobiliary Hospital) in the above multicenter retrospective cohort were used to construct a nomogram prediction model. Then, the model was evaluated by the index of concordance (C-Index) and the calibration curve.Results: After propensity score matching (PSM), Child-Pugh grade and MVI were independent risk factors for overall survival (OS) in ICC patients after curative resection. Major hepatectomy and MVI were independent risk factors for recurrence-free survival (RFS). The survival curves of OS and RFS before and after PSM in the MVI-positive groups were significantly different compared with those in the MVI-negative groups. Multivariate logistic regression results demonstrated that age, gamma-glutamyl transpeptidase (GGT), and preoperative image tumor number were independent risk factors for the occurrence of MVI. Furthermore, the prediction model in the form of a nomogram was constructed, which showed good prediction ability for both the training (C-index = 0.7622) and validation (C-index = 0.7591) groups, and the calibration curve showed good consistency with reality.Conclusion: MVI is an independent risk factor for the prognosis of ICC patients after curative resection. Age, GGT, and preoperative image tumor number were independent risk factors for the occurrence of MVI in ICC patients. The prediction model constructed further showed good predictive ability in both the training and validation groups with good consistency with reality. [ABSTRACT FROM AUTHOR]

Background: C5aR has been extensively studied in recent years as an essential component of the complement system. However, the role of C5aR in tumors has not been sufficiently investigated and summarized. The aim of this meta-analysis was to investigate the prognostic value of C5aR in solid tumors as well as the correlation between C5aR and clinicopathological features.Methods: Relevant study collection was performed in PubMed, Embase, Web of Science, BIOSIS Previews, Cochrane Library until July 10, 2021. Pooled hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Sensitivity analyses were performed to assess the robustness of this study, while publication bias was tested by Begg's and Egger's tests.Results: A total of 11 studies involving 1577 patients were included in the study. Our results suggest that the high-level C5aR expression in tumor tissue predicted unsatisfactory overall survival (OS) (HR = 1.92, 95% CI:1.47-2.50, P < 0.001) and recurrence-free survival (RFS) (HR = 2.19, 95% CI:1.47-3.27, P < 0.001). Besides, a higher level of C5aR expression was associated with larger tumor size (OR = 1.58, 95% CI: 1.18-2.10, P = 0.002) and the occurrence of metastases in lymph nodes (OR = 1.99, 95% CI: 1.46-2.72, P<0.001), whereas it was independent of tumor stage, vascular invasion and tumor differentiation.Conclusion: In conclusion, C5aR may be a potential biomarker for evaluating tumor prognosis and treatment. [ABSTRACT FROM AUTHOR]

Background: Current opinions on whether surgical patients with cervical cancer should undergo para-aortic lymphadenectomy at the same time are inconsistent. The present study examined differences in survival outcomes with or without para-aortic lymphadenectomy in surgical patients with stage IB1-IIA2 cervical cancer.Methods: We retrospectively compared the survival outcomes of 8802 stage IB1-IIA2 cervical cancer patients (FIGO 2009) who underwent abdominal radical hysterectomy + pelvic lymphadenectomy (n = 8445) or abdominal radical hysterectomy + pelvic lymphadenectomy + para-aortic lymphadenectomy (n = 357) from 37 hospitals in mainland China.Results: Among the 8802 patients with stage IB1-IIA2 cervical cancer, 1618 (18.38%) patients had postoperative pelvic lymph node metastases, and 37 (10.36%) patients had para-aortic lymph node metastasis. When pelvic lymph nodes had metastases, the para-aortic lymph node simultaneous metastasis rate was 30.00% (36/120). The risk of isolated para-aortic lymph node metastasis was 0.42% (1/237). There were no significant differences in the survival outcomes between the para-aortic lymph node unresected and resected groups. No differences in the survival outcomes were found before or after matching between the two groups regardless of pelvic lymph node negativity/positivity.Conclusion: Para-aortic lymphadenectomy did not improve 5-year survival outcomes in surgical patients with stage IB1-IIA2 cervical cancer. Therefore, when pelvic lymph node metastasis is negative, the risk of isolated para-aortic lymph node metastasis is very low, and para-aortic lymphadenectomy is not recommended. When pelvic lymph node metastasis is positive, para-aortic lymphadenectomy should be carefully selected because of the high risk of this procedure. [ABSTRACT FROM AUTHOR]

Background: Modified FOLFIRINOX and gemcitabine plus nab-paclitaxel (GEM-NAB) have been recommended as first-line therapies for advanced pancreatic cancer (PC). Due to the lack of evidence to directly compare them, we conducted this network meta-analysis to indirectly compare the effectiveness and toxicity of modified FOLFIRINOX and GEM-NAB.Methods: The eligible retrospective studies on treatments related to modified FOLFIRINOX and GEM-NAB up to 4 April 2020 were searched and assessed. We used the frequentist model to analyze the survival and toxicity data between different treatments. Pooled analysis for overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and events of toxicity were analyzed in this study.Results: Twenty-two studies were involved in this network meta-analysis. The comparisons on OS and PFS showed that modified FOLFIRINOX and GEM-NAB had similar treatment efficacy (OS: 1.13; 95% CI: 0.78-1.63; PFS: HR: 1.19; 95% CI: 0.85-1.67). GEM-NAB was more effective than modified FOLFIRINOX based on the result of ORR (RR: 1.43; 95% CI: 1.04-1.96). Moreover, our analysis showed a similar toxicity profile between modified FOLFIRINOX and GEM-NAB.Conclusions: The current evidence showed that modified FOLFIRINOX and GEM-NAB were similar in survival and toxicity. Many factors should be considered for in the formulation of optimal treatment, and our meta-analysis could provide some guidance to treatment selection in the first-line setting for advanced PC. [ABSTRACT FROM AUTHOR]

Background: Irreversible electroporation (IRE) is a local ablation technique utilizing high voltage, low energy direct current to create nanopores in cell membrane which disrupt homeostasis and leads to cell death. Previous reports have suggested IRE may have a role in treating borderline resectable and unresectable Stage 3 pancreatic tumors.Methods: Patients with Stage 3 pancreatic ductal adenocarcinoma (PDAC) will be enrolled in either a randomized, controlled, multicenter trial (RCT) or a multicenter registry study. Subjects enrolled in the RCT must have no evidence of disease progression after 3 months of modified FOLFIRINOX (mFOLFIRINOX) treatment prior to being randomization to either a control or IRE arm. Post-induction and post-IRE treatment for the control and IRE arms, respectively, will be left to the discretion of the treating physician. The RCT will enroll 528 subjects with 264 per arm and include up to 15 sites. All subjects will be followed for at least 24 months or until death. The registry study will include two cohorts of patients with Stage 3 PDAC, patients who received institutional standard of care (SOC) alone and those treated with IRE in addition to SOC. Both cohorts will be required to have undergone at least 3 months of SOC without progression prior to enrollment. The registry study will enroll 532 patients with 266 patients in each arm. All patients will be followed for at least 24 months or until death. The primary efficacy endpoint for both studies will be overall survival (OS). Co-primary safety endpoints will be 1) time from randomization or enrollment in the registry to death or new onset of Grade 4 adverse event (AE), and (2 high-grade complications defined as any AE or serious AE (SAE) with a CTCAE v5.0 grade of 3 or higher. Secondary endpoints will include progression-free survival, cancer-related pain, quality of life, and procedure-related pain for the IRE arm only.Discussion: These studies are intended to provide Level 1 clinical evidence and real-world data demonstrating the clinical utility and safety of the use of IRE in combination with chemotherapy in patients with Stage 3 PDAC.Trial Registration: Clinicaltrials.gov NCT03899636 and NCT03899649. Registered April 2, 2019. Food and Drug Administration (FDA) Investigational Device Exemption (IDE) trial G180278 approved on May 3, 2019. [ABSTRACT FROM AUTHOR]

Background: The number of colorectal cancer patients increases with age. The decision to go through major surgery can be challenging for the aged patient and the surgeon because of the heterogeneity within the older population. Differences in preoperative physical and cognitive status can affect postoperative outcomes and functional recovery, and impact on patients' quality of life.Methods/ Design: A prospective, observational, multicentre study including nine hospitals to analyse the impact of colon cancer surgery on functional ability, short-term outcomes (complications and mortality), and their predictors in patients aged ≥80 years. The catchment area of the study hospitals is 3.88 million people, representing 70% of the population of Finland. The data will be gathered from patient baseline characteristics, surgical interventional data, and pre- and postoperative patient-questionnaires, to an electronic database (REDCap) especially dedicated to the study.Discussion: This multicentre study provides information about colon cancer surgery's operative and functional outcomes on older patients. A further aim is to find prognostic factors which could help to predict adverse outcomes of surgery.Trial Registration: ClinicalTrials.gov ( NCT03904121 ). Registered on 1 April 2019. [ABSTRACT FROM AUTHOR]

Background: This study aimed to explore the efficacy and safety of sintilimab combined with induction chemotherapy (IC) in locally advanced head and neck squamous cell carcinoma (HNSCC) patients.Methods: A total of 163 patients were prospectively enrolled; 98 patients received IC only, and 65 patients received IC with sintilimab. Following neoadjuvant therapy, patients either underwent surgery (31.9%) or chemoradiotherapy (68.1%). Objective response rate (ORR), progression free survival (PFS), overall survival (OS), and toxicities between the two groups were compared.Results: The ORR in the IC group was significantly lower than that in the IC with sintilimab group (68.4% vs 84.6%, P = 0.019). Grade 3 or higher acute toxicity occurred in 15 (15.3%) and 12 (18.5%) patients in the IC and IC with sintilimab groups, respectively. However, this difference was not significant (P = 0.596). After follow-up with a median time of 28.0 months, the IC group had a 2-year PFS rate of 27% (95%CI: 18-36%), whereas the IC with sintilimab group had a 2-year PFS rate of 44% (95%CI: 32-56%), and this difference was significant (P = 0.041). The 2-year OS rates in the IC and IC with sintilimab groups were 61% (95%CI: 52-70%) and 70% (95%CI: 60-80%), respectively, the difference was not significant (P = 0.681).Conclusions: Addition of sintilimab to IC could provide longer PFS time than traditional chemotherapy regimen, without increasing the toxicity events. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of paclitaxel (PTX). There is no known prophylactic measure, although there are some reports of prevention with compression therapy using surgical gloves. On account of its predominantly subjective symptoms, it is difficult to exclude bias when assessing for CIPN. In this study, we assessed the effectiveness of the same procedure for the prevention of paclitaxel-induced PN based on a double-blind study design.Methods: The patients with early and recurrent breast cancer (with no prior PTX exposure) initiating weekly chemotherapy with PTX 80 mg/m2 were enrolled. Each patient donned two gloves on each hand at every PTX infusion. Two one-size-smaller gloves were donned on one hand (study side) and two normal-size gloves were donned on the other hand (control side) during 90 min from 30 min before the infusion to 30 min after the end of the infusion. Study side are blind for both patients and assessing physicians according to determination of the study side by research nurses in the chemotherapy unit. The primary outcome was the difference in the frequency of CIPN (motor/sensory) determined by the physician using the common terminology criteria for adverse events (CTCAE v4.0), with an evaluation at each cycle of PTX infusion. McNemar test was used to assess the primary outcome.Results: Between July 2017 and November 2018, 56 patients were enrolled and 49 patients were evaluated. Overall, Grade ≥ 2 PN (sensory) was observed in 30.6 and 36.7% in the study and control sides, respectively (McNemar p = 0.25). PN (motor) was observed in 4.1 and 6.1% in the study and control sides, respectively (McNemar p = 1.0).Conclusion: Surgical glove compression therapy showed no statistically significant effect on the incidence of PTX-induced PN.Trial Registrations: This study was registered with the University Hospital Medical Information Network (UMIN) Clinical Trials Registry managed by the National University Hospital Council of Japan ( UMIN000027944 ). Registered 26 June 2017. [ABSTRACT FROM AUTHOR]

Background: Benefit of carboplatin and dose-dense weekly paclitaxel (ddCT) in first line treatment of ovarian cancer patients has been different in Western and Asian studies. In the present study we compare progression-free survival (PFS) of ddCT to three-weekly carboplatin and paclitaxel (CT) in first-line treatment of ovarian carcinoma in a single institution in a Western population.Materials and Methods: We conducted a retrospective review of medical records from patients with ovarian carcinoma treated in a tertiary cancer center from 2007 to 2018. All patients treated with ddCT or CT in the first-line setting were included. Patients who received first-line bevacizumab were not included. PFS and overall survival (OS) were compared in a propensity score-matched cohort to address selection bias. Patients were matched according to age, ECOG performance status, CA 125, FIGO stage, residual disease, and histological subtype, in a 1:2 ratio.Results: Five hundred eighty-eight patients were eligible for propensity score matching, the final cohort consisted of 69 patients treated with ddCT and 138 CT group. Baseline characteristics were well-balanced. After a median follow-up of 65.1 months, median PFS was 29.3 vs 20.0 months, favouring ddCT treatment (p = 0.035). In the multivariate cox regression ddCT showed a 18% lower risk of progression (HR 0.82, 95% CI 0.68-0.99, p = 0.04). Overall survival data is immature, but suggested better outcomes for ddCT (not reached versus 78.8 months; p = 0.07).Conclusion: Our retrospective study has shown superior PFS of ddCT over CT regimen in first-line treatment of ovarian carcinoma in a Western population not treated with bevacizumab. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma is a relatively rare malignant tumor with a high incidence in young people. The development of tyrosine kinase inhibitors has brought the treatment of osteosarcoma into a new stage. Apatinib, a tyrosine kinase inhibitor specifically targeting VEGFR2, has been increasingly reported as a treatment for osteosarcoma with promising outcome parameters, but there has been no systematic analysis of the treatment of osteosarcoma by apatinib.Methods: A single-arm meta-analysis was performed, and published literature from PubMed, Web of Science, Embase, Cochrane Library, CNKI and Wan Fang databases as of March 1, 2021 was systematically retrieved. Quality assessment is carried out in accordance with a 20 item checklist form prepared by the Institute of Health Economics (IHE). Double arcsine transformation is performed to stabilize the variance of the original ratio. When I2 > 50%, the random effect model is used to calculate the pooled parameters; otherwise, the fixed effect model is used. We conducted subgroup analysis according to age and apatinib dose.Results: This meta-analysis included 11 studies of 356 Chinese patients with osteosarcoma. The pooled objective remission rate (ORR) of advanced or metastatic osteosarcoma treated by oral apatinib in Chinese patients was 0.27(95%CI = 0.18-0.38). The pooled disease control rate (DCR) was 0.57 (95%CI = 0.42-0.72). The pooled median progression-free survival (mPFS) and median total survival (mOS) were 5.18 months (95%CI = 4.03-6.33) and 10.87 months (95% CI = 9.40-12.33), respectively. More than 70% of adverse reactions were mild, the most common adverse reaction was hand-foot syndrome (HFMD), with an incidence of 0.46 (95%CI = 0.35-0.58), the second was hypertension, with an incidence of 0.40 (95%CI = 0.29-0.51).Conclusions: The efficacy of apatinib in the treatment of osteosarcoma is competitive with current evidence, and it is worth noting that its low cost can significantly improve patient compliance and increase therapeutic value. [ABSTRACT FROM AUTHOR]

Background: Lung cancer survivors need more options to improve quality of life (QoL). It is unclear to what extent patients with advanced stage disease are willing to participate in home-based physical activity (PA) and if these interventions improve QoL. The goal of our study was to determine interest in participating in our 3-month home-based walking regimen in patients with advanced stage lung cancer. We used a randomized design to evaluate for potential benefit in PA and patient-reported outcomes.Methods: We performed an open-label, 1:1 randomized trial in 40 patients with stage III/IV non-small cell lung cancer (NSCLC) evaluating enrollment rate, PA, QoL, dyspnea, depression, and biomarkers. Compared to usual care (UC), the intervention group (IG) received an accelerometer, in-person teaching session, and gain-framed text messages for 12 weeks.Results: We enrolled 56% (40/71) of eligible patients. Participants were on average 65 years and enrolled 1.9 years from diagnosis. Most patients were women (75%), and receiving treatment (85%) for stage IV (73%) adenocarcinoma (83%). A minority of patients were employed part-time or full time (38%). Both groups reported low baseline PA (IG mean 37 (Standard deviation (SD) 46) vs UC 59 (SD 56) minutes/week; p = 0.25). The IG increased PA more than UC (mean change IG + 123 (SD 212) vs UC + 35 (SD 103) minutes/week; p = 0.051)). Step count in the IG was not statistically different between baseline (4707 step/day), week 6 (5605; p = 0.16), and week 12 (4606 steps/day; p = 0.87). The intervention improved EORTC role functioning domain (17 points; p = 0.022) with borderline improvement in dyspnea (- 13 points; p = 0.051) compared to UC. In patients with two blood samples (25%), we observed a significant increase in soluble PD-1 (219.8 (SD 54.5) pg/mL; p < 0.001).Conclusions: Our pilot trial using a 3-month, home-based, mobile health intervention enrolled over half of eligible patients with stage III and IV NSCLC. The intervention increased PA, and may improve several aspects of QoL. We also identified potential biomarker changes relevant to lung cancer biology. Future research should use a larger sample to examine the effect of exercise on cancer biomarkers, which may mediate the association between PA and QoL.Clinical Trial Registration: Clinicaltrials.gov ( NCT03352245 ). [ABSTRACT FROM AUTHOR]

Background: To evaluate the efficacy and safety of recombinant human serum albumin /granulocyte colony-stimulating factor (rHSA/G-CSF) in breast cancer following receipt of cytotoxic agents.Methods: The phase 1b trial assessed the pharmacokinetics, pharmacodynamics, and safety of dose-escalation, ranging from rHSA/G-CSF 1800 μg, 2100 μg, and 2400 μg. Randomized controlled phase 2b trial was further conducted to ensure the comparative efficacy and safety of rHSA/G-CSF 2400 μg and rhG-CSF 5 μg/kg. In multicenter, randomized, open-label, parallel, phase 2 study, participants treated with anthracycline-containing chemotherapy were assigned in a ratio 1:1:1 to receive double delivery of rHSA/G-CSF 1200 μg, 1500 μg, and continuous rhG-CSF 5 μg/kg.Results: Between December 16, 2014, to July 23, 2018, a total of 320 patients were enrolled, including 25 individuals in phase 1b trial, 80 patients in phase 2b trial, and 215 participants in phase 2 study. The mean duration of agranulocytosis during the first chemotherapeutic intermission was observed as 1.14 ± 1.35 days in rHSA/G-CSF 1500 μg, which was comparable with that of 1.07 ± 0.97 days obtained in rhG-CSF control (P = 0.71). Safety profiles were assessed to be acceptable ranging from rHSA/G-CSF 1800 μg to 2400 μg, while the double delivery of HSA/G-CSF 2400 μg failed to meet the noninferiority in comparison with rhG-CSF.Conclusion: The prospective randomized controlled trials demonstrated that rHSA/G-CSF was efficacious and well-tolerated with an approachable frequency and expense of application for prophylactic management of agranulocytosis. The double delivery of rHSA/G-CSF 1500 μg in comparisons with paralleling G-CSF preparations is warranted in the phase 3 trial.Trial Registration: ClinicalTrials.gov identifiers: NCT02465801 (11/17/2014), NCT03246009 (08/08/2017), NCT03251768 (08/07/2017). [ABSTRACT FROM AUTHOR]

Background: Epidermal growth factor receptor (EGFR) is a target for cancer therapy as it is overexpressed in a wide variety of cancers. Therapeutic antibodies that bind EGFR are being evaluated in clinical trials as imaging agents for positron emission tomography and image-guided surgery. However, some of these antibodies have safety concerns such as infusion reactions, limiting their use in imaging applications. Nimotuzumab is a therapeutic monoclonal antibody that is specific for EGFR and has been used as a therapy in a number of countries.Methods: Formulation of IRDye800CW-nimotuzumab for a clinical trial application was prepared. The physical, chemical, and pharmaceutical properties were tested to develop the specifications to determine stability of the product. The acute and delayed toxicities were tested and IRDye800CW-nimotuzumab was determined to be non-toxic. Non-compartmental pharmacokinetics analysis was used to determine the half-life of IRDye800CW-nimotuzumab.Results: IRDye800CW-nimotuzumab was determined to be non-toxic from the acute and delayed toxicity study. The half-life of IRDye800CW-nimotuzumab was determined to be 38 ± 1.5 h. A bi-exponential analysis was also used which gave a t1/2 alpha of 1.5 h and t1/2 beta of 40.8 h.Conclusions: Here, we show preclinical studies demonstrating that nimotuzumab conjugated to IRDye800CW is safe and does not exhibit toxicities commonly associated with EGFR targeting antibodies. [ABSTRACT FROM AUTHOR]