Adapted EXTREME regimen in the first-line treatment of fit, older patients with recurrent or metastatic head and neck squamous cell carcinoma (ELAN-FIT): a multicentre, single-arm, phase 2 trial.

Background: A standard treatment for fit, older patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) is yet to be established. In the previous EXTREME trial, few older patients were included. We aimed to evaluate the efficacy and tolerance of an adapted EXTREME regimen in fit, older patients with recurrent or metastatic HNSCC.

Season of radiotherapy and outcomes of head & neck cancer patients in the MACH-NC & MARCH meta-analyses.

Background: A single institution retrospective study suggested that head and neck squamous cell cancer (HNSCC) patients receiving radiotherapy (RT) during "dark" season (fall/winter) may have better outcomes than those treated during "light" season (spring/summer), possibly secondary to seasonal variations in cell cycle progression. We investigated the impact of season of RT in two large, multi-institutional, prospective datasets of randomized trials.

Methods: Individual patient data from the MACH-NC and MARCH meta-analyses were analyzed.

Role of chemotherapy in patients with nasopharynx carcinoma treated with radiotherapy (MAC-NPC): an updated individual patient data network meta-analysis.

Background: The meta-analysis of chemotherapy for nasopharynx carcinoma (MAC-NPC) collaborative group previously showed that the addition of adjuvant chemotherapy to concomitant chemoradiotherapy had the highest survival benefit of the studied treatment regimens in nasopharyngeal carcinoma. Due to the publication of new trials on induction chemotherapy, we updated the network meta-analysis.

Methods: For this individual patient data network meta-analysis, trials of radiotherapy with or without chemotherapy in patients with non-metastatic nasopharyngeal carcinoma that completed accrual before Dec 31, 2016, were identified and updated individual patient data were obtained.

Intra-arterial hepatic bevacizumab and systemic chemotherapy in hepatic metastasis of colorectal cancer: A phase II multicentric trial in second-line treatment.

Introduction: Intra-arterial hepatic (IAH) treatment has shown promising results in the management of patients with unresectable colorectal liver metastases (CRLM) the prognosis of which is poor. Bevacizumab adjunction to standard chemotherapy has been shown to improve survival of this patient population. This prospective study was conducted to assess the efficacy and safety of IAH bevacizumab combined to systemic chemotherapy after first-line treatment failure in patients with CRLM.

ANtiangiogenic Second-line Lung cancer Meta-Analysis on individual patient data in non-small cell lung cancer: ANSELMA.

Background: Now that immunotherapy plus chemotherapy (CT) is one standard option in first-line treatment of advanced non-small cell lung cancer (NSCLC), there exists a medical need to assess the efficacy of second-line treatments (2LT) with antiangiogenics (AA). We performed an individual patient data meta-analysis to validate the efficacy of these combinations as 2LT.

Methods: Randomised trials of AA plus standard 2LT compared to 2LT alone that ended accrual before 2015 were eligible.

Cost-effectiveness of prophylactic cranial irradiation in stage III non-small cell lung cancer.

Introduction: In stage III non-small cell lung cancer (NSCLC), prophylactic cranial irradiation (PCI) reduces the brain metastases incidence and prolongs the progression-free survival without improving overall survival. PCI increases the risk of toxicity and is currently not adopted in routine care. Our objective was to assess the cost-effectiveness of PCI compared with no PCI in stage III NSCLC from a Dutch societal perspective.

Meta-analysis of chemotherapy in nasopharynx carcinoma (MAC-NPC): An update on 26 trials and 7080 patients.

Purpose: Chemotherapy, when added to radiotherapy, improves survival in locally advanced nasopharyngeal carcinoma (NPC). This article presents the second update of the Meta-Analysis of Chemotherapy in NPC.

Methods: Published or unpublished randomized trials assessing radiotherapy (±a second chemotherapy timing) with/without chemotherapy in non-metastatic NPC patients were identified.

Association of different fractionation schedules for prophylactic cranial irradiation with toxicity and brain metastases-free survival in stage III non-small cell lung cancer: A pooled analysis of individual patient data from three randomized trials.

We assessed the impact of different PCI fractionation schedules (30 Gy in 10 versus 15 fractions) on brain metastases-free survival (BMFS) and toxicity in stage III NSCLC. Our results suggest that 30 Gy in 10 fractions is associated with increased toxicity, while no conclusive evidence of improving BMFS was seen with this schedule.

BEAUTY and the breast: is adjuvant chemotherapy the right time for a beauty boost? Lessons learned from a large randomized controlled trial.

Purpose: Beauty care (BTC) is offered at many cancer hospitals having a great uptake among patients. Nevertheless, its benefits in the Quality of life (QoL) of cancer survivors have not been assessed so far.

Methods: Our study aims to determine whether BTC improves patients' QoL related to their body image measured by the BRBI scale of the QLQ-BR23 questionnaire at the end of adjuvant chemotherapy, after breast cancer (BC) surgery.

Chemotherapy and radiotherapy in locally advanced head and neck cancer: an individual patient data network meta-analysis.

Background: Randomised, controlled trials and meta-analyses have shown the survival benefit of concomitant chemoradiotherapy or hyperfractionated radiotherapy in the treatment of locally advanced head and neck cancer. However, the relative efficacy of these treatments is unknown. We aimed to determine whether one treatment was superior to the other.

Individual patient data meta-analysis of prophylactic cranial irradiation in locally advanced non-small cell lung cancer.

Background: Prophylactic cranial irradiation (PCI) was compared to observation in several randomized trials (RCTs), and a reduction greater than 50% was shown regarding the incidence of brain metastases (BM). However, none of these studies showed an improvement of overall survival (OS), possibly related to relatively small sample sizes and short follow-up. The aim of this meta-analysis was therefore to assess the impact of PCI on long term OS for stage III non-small cell lung cancer (NSCLC) compared to observation based on the pooled updated individual patient RCT data.

Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group.

Background And Purpose: The Meta-Analysis of Chemotherapy in squamous cell Head and Neck Cancer (MACH-NC) demonstrated that concomitant chemotherapy (CT) improved overall survival (OS) in patients without distant metastasis. We report the updated results.

Materials And Methods: Published or unpublished randomized trials including patients with non-metastatic carcinoma randomized between 1965 and 2016 and comparing curative loco-regional treatment (LRT) to LRT + CT or adding another timing of CT to LRT + CT (main question), or comparing induction CT + radiotherapy to radiotherapy + concomitant (or alternating) CT (secondary question) were eligible.

Predictive classifier for intensive treatment of head and neck cancer.

Background: This study was designed to test the hypothesis that the effectiveness of intensive treatment for locoregionally advanced head and neck cancer (LAHNC) depends on the proportion of patients' overall event risk attributable to cancer.

Methods: This study analyzed 22,339 patients with LAHNC treated in 81 randomized trials testing altered fractionation (AFX; Meta-Analysis of Radiotherapy in Squamous Cell Carcinomas of Head and Neck [MARCH] data set) or chemotherapy (Meta-Analysis of Chemotherapy in Head and Neck Cancer [MACH-NC] data set). Generalized competing event regression was applied to the control arms in MARCH, and patients were stratified by tertile according to the ω score, which quantified the relative hazard for cancer versus competing events.

Role of chemotherapy in 5000 patients with head and neck cancer treated by curative surgery: A subgroup analysis of the meta-analysis of chemotherapy in head and neck cancer.

Objective: To evaluate the effect of chemotherapy added to a surgical locoregional treatment (LRT) for patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Materials And Methods: We studied the sub-group of trials with surgical LRT included in the meta-analysis on chemotherapy in head and neck cancer (MACH-NC). Data from published and unpublished randomized trials comparing the addition of chemotherapy to LRT in HNSCC patients were sought using electronic database searching for the period 1965-2000, hand searching and by contacting experts in the field.

Quality of life and cost of strategies of two chemotherapy lines in metastatic colorectal cancer: results of the FFCD 2000-05 trial.

: This study compared the cost and quality of life (QoL) of 407 advanced colorectal cancer patients, randomly assigned to receive LV5FU2 followed by FOLFOX6 (sequential strategy) or FOLFOX6 followed by FOLFIRI (combination strategy). : Costs were compared from the French health insurance perspective, until the end of the second line of treatment. Consumed resources, collected during the trial, included medicines, hospitalizations, examinations, and transportation.

LACE-Bio: Validation of Predictive and/or Prognostic Immunohistochemistry/Histochemistry-based Biomarkers in Resected Non-small-cell Lung Cancer.

Background: Complete resection of non-small-cell lung cancer (NSCLC) offers the potential for cure after surgery and adjuvant chemotherapy. Patients may not benefit and may experience severe toxicity. There are no validated molecular tools to allow better patient selection.

Impact of missing individual patient data on 18 meta-analyses of randomised trials in oncology: Gustave Roussy experience.

Objective: To compare the characteristics, quality and treatment effects of randomised clinical trials (RCTs) by individual patient data (IPD) availability, in trials eligible for 18 IPD meta-analyses (MA).

Design: Trial characteristics, risk of bias (RoB) and hazard ratio (HR) for overall survival were extracted from IPD-MA publications and/or RCTs publications. Data for the RoB assessment were extracted for a subset of 73 RCTs.

Prognostic impact of HPV-associated p16-expression and smoking status on outcomes following radiotherapy for oropharyngeal cancer: The MARCH-HPV project.

Background And Purpose: Evaluate the prognostic and predictive impact of HPV-associated p16-expression and assess the combined prognostic impact of p16 and smoking on altered fractionated radiotherapy (AFRT) for oropharyngeal cancer (OPC) within the frames of the update of the Meta-Analysis of Radiotherapy in Carcinomas of Head and neck (MARCH).

Materials And Methods: Patients with OPC, known tumor p16-status and smoking history were identified from the MARCH update, resulting in a dataset of 815 patients from four randomized trials (RTOG9003, DAHANCA6&7, RTOG0129, ARTSCAN). Analysis was performed using a Cox model stratified by trial and adjusted on gender, age, T-stage, N-stage, type of radiotherapy fractionation, p16, smoking.

Role of radiotherapy fractionation in head and neck cancers (MARCH): an updated meta-analysis.

Background: The Meta-Analysis of Radiotherapy in squamous cell Carcinomas of Head and neck (MARCH) showed that altered fractionation radiotherapy is associated with improved overall and progression-free survival compared with conventional radiotherapy, with hyperfractionated radiotherapy showing the greatest benefit. This update aims to confirm and explain the superiority of hyperfractionated radiotherapy over other altered fractionation radiotherapy regimens and to assess the benefit of altered fractionation within the context of concomitant chemotherapy with the inclusion of new trials.

Methods: For this updated meta-analysis, we searched bibliography databases, trials registries, and meeting proceedings for published or unpublished randomised trials done between Jan 1, 2009, and July 15, 2015, comparing primary or postoperative conventional fractionation radiotherapy versus altered fractionation radiotherapy (comparison 1) or conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone (comparison 2).

Pooled Analysis of the Prognostic and Predictive Effects of TP53 Comutation Status Combined With KRAS or EGFR Mutation in Early-Stage Resected Non-Small-Cell Lung Cancer in Four Trials of Adjuvant Chemotherapy.

Purpose Our previous work evaluated individual prognostic and predictive roles of TP53, KRAS, and EGFR in non-small-cell lung cancer (NSCLC). In this analysis, we explore the prognostic and predictive roles of TP53/KRAS and TP53/EGFR comutations in randomized trials of adjuvant chemotherapy versus observation. Patients and Methods Mutation analyses (wild-type [WT] and mutant) for TP53, KRAS, and EGFR were determined in blinded fashion in multiple laboratories.

Prognostic value of tumor mutations in radically treated locally advanced non-small cell lung cancer patients.

Introduction: Chemo-radiation is standard treatment in locally advanced non-small cell lung cancers (NSCLC). The prognostic value of mutations has been poorly explored in this population.

Results: Clinical data were collected from 190 patients and mutational profiles were obtained in 78 of them; 58 (74%) were males, 31 (40%) current smokers, 47/31 stage IIIA/IIIB and 40 (51%) adenocarcinoma.

[New applications for individual participant data meta-analyses of randomized trials].

Meta-analyses of randomized trials using individual-participant data, which represent the highest level of evidence for the evaluation of a treatment effect, are now used in different contexts in clinical research. This article aims at reviewing some of these new applications. Meta-analyses are increasingly used in economic evaluation, which implies new measure outcomes of the treatment effect, as well as in biomarkers evaluations thanks to their higher statistical power and the possibility to validate findings on independent data.

A phase II open-label multicenter study of gefitinib in combination with irradiation followed by chemotherapy in patients with inoperable stage III non-small cell lung cancer.

Background: Gefitinib is an oral EGFR tyrosine kinase inhibitors which may act as a radiosensitizer.

Patients And Methods: This phase II study evaluated the efficacy of gefitinib 250 mg once daily in combination with thoracic radiotherapy (66 Gy in 6.5 weeks, 2 Gy/day, 5 fractions/week) followed by consolidation chemotherapy (IV cisplatin and vinorelbine) as first line treatment in a population of unselected stage IIIB NSCLC patients according to EGFR mutation status.

Prognostic and Predictive Effect of TP53 Mutations in Patients with Non-Small Cell Lung Cancer from Adjuvant Cisplatin-Based Therapy Randomized Trials: A LACE-Bio Pooled Analysis.

Introduction: Tumor protein p53 gene (TP53) mutations are common in stage I through III non-small cell lung cancer, but clinical trials have shown inconsistent results regarding their relationship to the effects of adjuvant therapy. The objective is to clarify their putative prognostic and predictive effects.

Methods: A pooled analysis of TP53 mutations (exons 5-8) was conducted in four randomized trials (the International Adjuvant Lung Cancer Trial, J BRonchus 10, Cancer and Leukemia Group B-9633, and Adjuvant Navelbine International Trialist Association trial) of platinum-based adjuvant chemotherapy (ACT) versus observation (OBS).