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Pembrolizumab is a standard-of-care for advanced non-small-cell lung cancer (NSCLC). We assessed pembrolizumab as adjuvant therapy for completely resected stage IB-IIIA NSCLC.In this randomised, triple-blind, phase 3 trial (PEARLS/KEYNOTE-091), patients were recruited from 196 medical centres in 29 countries. Eligible patients were aged 18 years or older, with completely resected, pathologically confirmed stage IB (tumours of ≥4 cm in diameter), II, or IIIA NSCLC per the American Joint Committee on Cancer staging system (7th edition) of any histology or PD-L1 expression level, and an Eastern Cooperative Oncology Group performance status of 0 or 1; adjuvant chemotherapy was to be considered for stage IB disease and was strongly recommended for stage II and IIIA disease, according to national and local guidelines. Using a central interactive voice-response system, eligible participants were randomly assigned (1:1), using a minimisation technique and stratified by disease stage, previous adjuvant chemotherapy, PD-L1 expression, and geographical region, to pembrolizumab 200 mg or placebo, both administered intravenously every 3 weeks for up to 18 cycles. Participants, investigators, and analysts were masked to treatment assignment. Dual primary endpoints were disease-free survival in the overall population and in the population with PD-L1 tumour proportion score (TPS) of 50% or greater. Efficacy was assessed in the intention-to-treat (ITT) population (ie, all participants randomly assigned to a treatment group). Safety was assessed in all participants randomly assigned to treatment who received at least one dose of study treatment. Here we report results of the second interim analysis, prespecified to occur when approximately 118 disease-free survival events had occurred in the PD-L1 TPS of 50% or greater population. This study is registered with ClinicalTrials.gov, NCT02504372, and is active but not recruiting.Between Jan 20, 2016, and May 6, 2020, 1177 (60%) of 1955 screened participants were randomly assigned to pembrolizumab (n=590, including n=168 with PD-L1 TPS of ≥50%) or placebo (n=587; including n=165 with PD-L1 TPS of ≥50%) and included in the ITT population. Median follow-up as of data cutoff (Sept 20, 2021) for this interim analysis was 35·6 months (IQR 27·1-45·5). In the overall population, median disease-free survival was 53·6 months (95% CI 39·2 to not reached) in the pembrolizumab group versus 42·0 months (31·3 to not reached) in the placebo group (HR 0·76 [95% CI 0·63-0·91], p=0·0014). In the PD-L1 TPS of 50% or greater population, median disease-free survival was not reached in either the pembrolizumab group (95% CI 44·3 to not reached) or the placebo group (95% CI 35·8 to not reached; HR 0·82 [95% CI 0·57-1·18]; p=0·14). Grade 3 or worse adverse events occurred in 198 (34%) of 580 participants who received pembrolizumab and 150 (26%) of 581 participants who received placebo. Grade 3 or worse events that occurred in at least ten participants in either treatment group were hypertension (35 [6%]) and pneumonia (12 [2%]) with pembrolizumab and hypertension (32 [6%]) with placebo. Serious adverse events occurred in 142 (24%) participants in the pembrolizumab group and 90 (15%) in the placebo group; serious adverse events that occurred in more than 1% of participants were pneumonia (13 [2%]), pneumonitis (12 [2%]), and diarrhoea (seven [1%]) with pembrolizumab and pneumonia (nine [2%]) with placebo. Treatment-related adverse events led to death in four (1%) participants treated with pembrolizumab (one due to both cardiogenic shock and myocarditis, one due to both septic shock and myocarditis, one due to pneumonia, and one due to sudden death) and in no participants treated with placebo.Pembrolizumab significantly improved disease-free survival compared with placebo and was not associated with new safety signals in completely resected, PD-L1-unselected, stage IB-IIIA NSCLC. Pembrolizumab is potentially a new treatment option for stage IB-IIIA NSCLC after complete resection and, when recommended, adjuvant chemotherapy, regardless of PD-L1 expression.Merck Sharpamp; Dohme, a subsidiary of Merckamp; Co.

Histopathological growth patterns (HGPs) are a reliable, reproducible, and strong prognostic biomarker that can be assessed on haematoxylin and eosin-stained sections of resected colorectal liver metastases (CRLM). Assessment estimates the relative fraction of the tumour–liver interface for each of the three growth patterns; the desmoplastic HGP reflects good prognosis. Whether preoperative chemotherapy affects the HGP is currently unclear. The present international multicentre study evaluates this in an original cohort of 877 consecutive patients treated in the Netherlands, an external validation cohort of 1,203 consecutive patients treated in the USA, and a post hoc analysis from the phase III randomised controlled European Organization for Research and Treatment of Cancer (EORTC) 40983 trial (n = 70). All patients underwent resection of CRLM with or without preoperative systemic chemotherapy. Trial patients were randomised between perioperative chemotherapy and resection or resection alone. HGPs were determined according to consensus guidelines and compared for preoperative treatment status. Data from three separate tumour regression grading systems were available for the trial cohort. These were correlated with HGP stratified for treatment arm. In the original cohort, the average presence of desmoplastic HGP was 43% for chemo-naïve versus 67% for preoperatively treated patients (p < 0.001). A significant association between chemotherapy and desmoplastic HGP was found on multivariable analysis (β [95% confidence interval, CI]: 24.57 [18.28–30.87], p < 0.001). In the validation cohort, the average presence of desmoplastic HGP was 40% for chemo-naïve versus 63% for preoperatively treated patients (p < 0.001). This association remained on multivariable analysis (β [95% CI]: 24.18 [18.70–29.66], p < 0.001). In the EORTC 40983 trial, the average desmoplastic HGP presence was 33% in the resection arm versus 61% in the chemotherapy arm (p = 0.005). Chemotherapy was independently associated with an increase in desmoplastic HGP (β [95% CI]: 23.29 [1.78–44.79], p = 0.022). All three tumour regression gradings were significantly associated with the desmoplastic HGP in the chemotherapy arm (all p < 0.04). None were associated in the resection arm (all p > 0.11). Preoperative chemotherapy induces histopathological changes that alter the HGP of CRLM.

Adjuvant colon cancer (CC) therapy and survival have greatly evolved over the last decades. Research shifted towards a more biological tumour understanding and unlocked new therapies and disease mo...

The primary objective of this study is to evaluate the clinical significance of RANK/L expression, in both a retrospective cohort of surgically resected stage I-III NSCLC (Lungscape) and a randomized clinical trial-cohort (SPLENDOUR) of advanced NSCLC treated with chemotherapy alone or in combination with denosumab.RANK-L expression was assessed on tissue microarrays (TMAs) in Lungscape and whole sections in SPLENDOUR, using immunohistochemistry, with H-scores values 0 indicating positivity. Prevalence of RANK positivity and its association with clinicopathological characteristics, and patient outcome was explored in a subset of the ETOP Lungscape cohort and in SPLENDOUR. Also investigated were the prevalence of RANK overexpression (proportion of positive cancer cells ≥ 50%) in the Lungscape cohort, and RANK-L in the SPLENDOUR trial.In the Lungscape cohort, RANK expression was assessed at a median follow-up of 46 months (N = 488 patients; 4 centers); 35% were female, 44/49/6% adenocarcinomas (AC)/squamous cell carcinomas (SCC)/other, 48/27/25% with stage I/II/III. Median RFS/TTR/OS were 58/Not reached/74 months. Prevalence of RANK expression was 31% (95%CI:27%-35%); significantly higher in AC: 50% (95%CI:43%-57%) vs SCC: 12% (95%CI:8%-16%) (p 0.001); more frequent in females (42% vs 25%, p 0.001) and tumors ≤ 4 cm (35.3% vs 23.3%, p = 0.0065). No association with outcome was found. In the SPLENDOUR trial (463 patients), the prevalence of membranous and cytoplasmic RANK positivity was 34% (95%CI:30%-38%) and 9% (95%CI:7%-12%), respectively, while prevalence for RANK-L was 5% (95%CI:3%-7%) and 36% (95%CI:31%-40%), respectively. Cytoplasmic RANK-L positivity was more common among females (47% vs 31%, p = 0.001) and in non-SCC histology (45% vs 10%, p 0.0001). At the pre-specified 1% significance level, no prognostic or predictive effect was found.Both cohorts indicate that RANK expression is more common in adenocarcinoma/non-squamous NSCLC and in female patients. No prognostic effect is found, and in the clinical trial involving addition of denosumab to chemotherapy no predictive effect is detected.

Objectives: Exercise has been reported to alleviate disease as well as treatment impact in patients with lung cancer. Nevertheless, there is limited information available regarding the perception of lung cancer dedicated healthcare professionals’ and their advice on exercise. Materials and Methods: An online survey exploring healthcare professionals’ practice patterns, perceptions, barriers, and facilitators of exercise in patients with lung cancer was conducted within members of the EORTC Lung Cancer Group (LCG). Results: One hundred forty-one healthcare providers completed the survey, mainly medical and radiation oncologists. Overall, 63% of the study participants declared that they frequently assessed exercise level in their patients, and 43% of them reinforced the importance of exercise. However, only 10% referred patients to an exercise program or specialist. Although the majority of the respondents had a positive perception regarding the benefits and safety of exercise (even in patients with advanced disease and/or bone metastasis), two-thirds of clinicians reported not having adequate training about exercise counselling. Moreover, 53% reported to lack of knowledge of guidelines referring to exercise in patients with cancer. Several obstacles and facilitators to improve exercise promotion in lung cancer care were identified. Conclusion: Healthcare providers recognize the relevance and feasibility of exercise as part of cancer treatment intervention, but specific pathways to do the referral are frequently missing. Future structured and well-designed strategies and initiatives are needed to support an effective referral in order to implement exercise interventions routinely in clinical practice.

PURPOSE The PETACC 6 trial investigates whether the addition of oxaliplatin to preoperative capecitabine-based chemoradiation and postoperative capecitabine improves disease-free survival (DFS) in locally advanced rectal cancer. METHODS Between November 2008 and September 2011, patients with rectal adenocarcinoma within 12 cm from the anal verge, T3/4 and/or node positive, were randomly assigned to 5 weeks preoperative capecitabine-based chemoradiation (45-50.4 Gy) followed by six cycles of adjuvant capecitabine, both without (control arm, 1) or with (experimental arm, 2) oxaliplatin. The primary end point was improvement of 3-year DFS by oxaliplatin from 65% to 72% (hazard ratio [HR], 0.763). RESULTS A total of 1,094 patients were randomly assigned (intention to treat), and 1,068 eligible patients started their allocated treatment (arm 1, 543; arm 2, 525), with completion of protocol treatment in 68% (arm 1) v 54% (arm 2). A higher rate of grade 3/4 adverse events was reported in the experimental arm (14.4% v 37.3% and 23.4% v 46.6% for neoadjuvant and adjuvant treatment, respectively). At a median follow-up of 68 months (interquartile range, 58-74 months), 157 and 156 DFS events were observed in arms 1 and 2, respectively (adjusted HR, 1.02; 95% CI, 0.82 to 1.28; P = .835). Three-year DFS rate was not different, with 76.5% (95% CI, 72.7% to 79.9%) in arm 1, which is higher than anticipated, and 75.8% (95% CI, 71.9% to 79.3%) in arm 2. The 7-year DFS and overall survival (OS) rates were not different as well, with DFS of 66.1% v 65.5% (HR, 1.02) and OS of 73.5% v 73.7% (HR, 1.19) in arms 1 and 2, respectively. Subgroup analyses revealed heterogeneity in treatment effect according to German versus non-German site location, without detectable confounding factors in multivariable analysis. CONCLUSION The addition of oxaliplatin to preoperative capecitabine-based chemoradiation and postoperative adjuvant chemotherapy impairs tolerability and feasibility and does not improve efficacy.

141 Background: Treatment for patients (pts) with metastatic colorectal cancer (mCRC) with unresectable liver metastases (mets) is usually chemotherapy (CT) +/- local ablative treatments. Immunotherapy (IO) effect is disappointing in mCRC with pMMR status so testing strategies to promote immune activation is key. Previous studies show that local ablative treatments may induce local immune activation and prime for IO response. Methods: This multi-center non-randomised early phase II study aims to test whether local liver therapy in combination with durvalumab and tremelimumab (durv/trem) will lead to immune response in liver metastases untreated locally. Eligible pts had non-resectable liver predominant mCRC and at least stable disease following 3-6 months first- or second line CT. Liver mets were amenable to radiofrequency ablation (RFA) or stereotactic radiotherapy (SBRT) allowing a total ablated volume of at least 25 cm3. At least 2 measurable liver or 1 liver and 1 extrahepatic lesions were left untreated locally. Tremelimumab 75 mg and durvalumab 1500 mg were given for 4 cycles followed by durvalumab 1500 mg every 4 weeks. During cycle 1, RFA and SBRT were performed concurrently.Primary endpoint was ORR per iRECIST in lesions untreated locally; secondary endpoints included feasibility and safety and progression free survival (PFS). According to an optimal Simon’s two-stage design to reject a ORR ≤ 10% with power of 90% under a ORR of 25% using a one-sided alpha of 5%, the study should be early stopped if there were ≤2 responses among the 21 first patients enrolled in the per protocol (PP) population (stage I) while ≥ 11 responses among 66 patients were needed to declare success. Results: Between March 2019 and March 2021, 23 pts were recruited from 6 centers in 4 countries; 21 pts started protocol treatment; 13 pts were treated with RFA; 8 pts with SBRT but 1 pt was ineligible out of 21. In the PP population (20 pts), median age was 57. Response to previous systemic CT was PR (75%) and SD (25%). No pt had prior surgery or local treatment to the liver. 60% had limited extra-hepatic disease (up to 2 sites). Median treatment duration was 85.0 days; all 20 pts received planned local ablative treatment. At best response assessment, 0% of patients had a CR or PR, 45% had SD and 55% PD. Median PFS was 2.2 months (95% CI: 1.8-3.6). At a median follow up of 11 months, 55% of pts had died. The study was closed due to futility. In patients treated with RFA + durv/trem, 30.8% had grade 3 toxicity; for SBRT +durv/trem it was 50%. Conclusions: In this phase II trial, combining IO with local ablative therapy in liver predominant mCRC did not result in responses in lesions untreated locally. Further strategies are required to improve IO response in this clinical setting. Clinical trial information: 2017-001375-22 .

This work focuses on the modification of two classical phase II trials designs, the A’Hern design, a single-arm single-stage design, and the Sargent and Goldberg design introduced in the context of flexible screening designs. In the first part of the paper, we have proposed a drift-adjusted A’Hern design, a hybrid design combining the A’Hern design and the Sargent and Goldberg design. Indeed, classical single-arm phase II designs such as the A’Hern design are still widely used in oncology. Conducting randomized comparative phase II trials may be challenging in many settings due to the increased sample size and this despite larger type 1 errors. Randomized non-comparative phase II designs first introduced by Herson and Carter include a simultaneous randomized standard-treatment reference arm to detect any drift in the reference arm assumption, but the trial is analyzed against historical controls as if it were a single-arm study. However, not incorporating at all an internal control arm in the trial design has been criticized in the literature. Our new design takes into account the observed response rate in a non-comparative reference arm to reduce the trial’s risk of a false-positive conclusion. In the second part, we have proposed an alternative strategy to determining the sample size of the screened selection design. The latter, introduced in recent years by Yap et al. and Wu et al., extended the Sargent and Goldberg design to include a comparison to a historical control. However, their sample size computations may have potential weaknesses, which motivated us to revisit the existing approaches. A detailed simulation study has been carried out to evaluate the operating characteristics of the drift-adjusted A’Hern design and the different sample size strategies of the screened selection designs.

8512 Background: At the second interim analysis (IA2) of the triple-blind, phase 3 PEARLS/KEYNOTE-091 study (NCT02504372), pembrolizumab significantly improved DFS compared with placebo in patients (pts) with completely resected stage IB (T ≥4 cm) to IIIA NSCLC per AJCC v7, regardless of PD-L1 expression (N = 1177, HR 0.76, 95% CI 0.63-0.91, P = 0.0014). We present DFS in subgroups related to surgery, disease burden, and adjuvant chemotherapy use. Methods: Pts had pathologically confirmed, completely resected stage IB (T ≥4 cm) to IIIA NSCLC of any PD-L1 expression and ECOG PS 0-1. Systematic complete or lobe-specific mediastinal lymph node dissection was recommended; minimally, the subcarinal and 1 lobe-specific lymph node must have been examined. Adjuvant chemotherapy of ≤4 cycles was given as indicated by local guidelines. Eligible pts were randomized 1:1 to pembrolizumab 200 mg or placebo Q3W for 18 doses (̃1 y). Treatment effects on DFS were assessed in prespecified subgroups of with and without adjuvant chemotherapy and in exploratory subgroups defined by surgery type, pN stage, tumor size, no. of adjuvant chemotherapy cycles, and adjuvant regimen; only subgroups of > 50 pts were analyzed. Data cutoff for IA2 was September 20, 2021 (median time from randomization to cutoff, 35.6 mo). Results: By surgery type, the HR (95% CI) for DFS was 0.78 (0.64-0.96) for lobectomy (n = 925), 0.85 (0.43-1.69) for bilobectomy (n = 92), and 0.71 (0.40-1.24) for pneumonectomy (n = 127). For subgroups based on nodal status, HR (95% CI) for DFS was 0.63 (0.46-0.86) for pN0 (n = 490), 0.77 (0.57-1.03) for pN1 (n = 456), and 1.00 (0.71-1.41) for pN2 (n = 231). By tumor size, and irrespective of nodal status, the HR (95% CI) for DFS was 0.91 (0.69-1.20) for size ≤4 cm (n = 491) and 0.70 (0.55-0.89) for size > 4 cm (n = 685). The HR (95% CI) for DFS was 0.73 (0.60-0.89) in pts who received adjuvant chemotherapy (n = 1010) and 1.25 (0.76-2.05) in those who did not (n = 167). Among pts who received adjuvant chemotherapy, HR (95% CI) for DFS by number of cycles was 0.59 (0.28-1.26) for 1-2 (n = 67) and 0.74 (0.61-0.91) for 3-4 (n = 943); by regimen, it was 0.74 (0.55-0.98) for cisplatin + vinorelbine (n = 491), 0.51 (0.31-0.83) for carboplatin + vinorelbine (n = 151), 1.21 (0.73-1.98) for carboplatin + paclitaxel (n = 135), 0.65 (0.30-1.40) for cisplatin + gemcitabine (n = 57), and 0.68 (0.41-1.14) for other regimen (n = 176). Conclusions: Pembrolizumab generally improved DFS versus placebo regardless of type of surgery, lymph node involvement, tumor size, and type and extent of adjuvant chemotherapy in pts with completely resected stage IB (T ≥4 cm) to IIIA NSCLC. These data support the benefit of pembrolizumab as adjuvant therapy for early-stage NSCLC following complete resection and, if indicated, adjuvant chemotherapy. Clinical trial information: NCT02504372.

Background: Perioperative chemotherapy plus surgery is one recommended standard treatment for patients with resectable gastric and esophageal cancer. Even with a multimodality treatment more than half of patients will relapse following surgical resection. Patients who have a poor response to neoadjuvant chemotherapy and have an incomplete (R1) resection or have metastatic lymph nodes in the resection specimen (N+) are especially at risk of recurrence. Current clinical practice is to continue with the same chemotherapy in the adjuvant setting as before surgery. In the phase II randomized EORTC VESTIGE trial (NCT03443856), patients with high risk resected gastric or esophageal adenocarcinoma will be randomized to either adjuvant chemotherapy (as before surgery) or to immunotherapy with nivolumab and low dose ipilimumab (nivolumab 3 mg/kg IV Q2W plus Ipilimumab 1 mg/kg IV Q6W for 1 year). The primary endpoint of the study is disease free survival, with secondary endpoints of overall survival, safety and toxicity, and quality of life. This is an open label randomized controlled multi-center phase-2 superiority trial. Patients will be randomized in a 1:1 ratio to study arms. The trial will recruit 240 patients; recruitment commenced July 2019 and is anticipated to take 30 months. Detailed inclusion/exclusion criteria, toxicity management guidelines, and statistical plans for EORTC VESTIGE are described in the manuscript. Clinical Trial Registration: The trial is registered with www.ClinicalTrials.gov, identifier: NCT03443856.

HER2-targeted therapy with trastuzumab and (CF/X) prolonged overall survival (OS) in metastatic HER2neu+ gastric carcinoma (GC). Lapatinib inhibits both EGFR and HER2neu. We investigated the efficacy and safety of lapatinib with epirubicin (E) + CF/X in GC according to HER2neu and EGFR status. Tumors from chemotherapy-naive patients were screened centrally by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). Patients with EGFR and/or HER2neu expression or amplification were allocated to three strata based on EGFR/HER2neu status and were randomized to lapatinib (arm A) or placebo (arm B), with 6 cycles of ECF or ECX (investigator-selected). The primary endpoint was progression-free survival (PFS) in stratum 3. 29 of 72 screened patients were randomized to strata 1 (HER2neu+: by FISH and IHC, n = 6), 2 (HER2neu−: by FISH/+ by IHC, n = 5) and 3 (HER2neu−/EGFR+, n = 18), of which 28 patients were eligible (14 per arm). Enrollment was curtailed after announcement of the negative LOGiC trial results. Median PFS was 8.0 versus 5.9 months (HR = 0.86, 95% CI 0.37–1.99) in the per protocol population, and 8.0 versus 6.3 months (HR = 0.85, 95% CI 0.30–2.46) for stratum 3, in the lapatinib versus placebo arm respectively. Median OS was 13.8 versus 10.1 months, respectively (HR = 0.90, 95% CI 0.35–2.27). There were no safety concerns. Central EGFR and HER2neu stratification by IHC and FISH can be used for further pan-HER strategies. Lapatinib with ECF/X was well tolerated, but did not show clear activity in patients with metastatic GC.

The role of multidisciplinary treatment including surgery for liver metastases from gastric cancer (LMGC) is controversial. Studies to answer this clinical question are increasing in number, but all published data thus far are based on retrospective analyses with limited sample sizes. Thus, the European Organisation for Research and Treatment of Cancer (EORTC) Gastrointestinal Tract Cancer Group (GITCG) and the Japan Clinical Oncology Group (JCOG) Stomach Cancer Study Group (SCSG) initiated a collaboration to develop an optimal treatment strategy for LMGC. Before planning a prospective study, a questionnaire was sent out to the network members of both groups in June 2016 to clarify current common practice in each region. Sixty-seven sites from 17 countries in the EORTC network and 55 sites from Japan responded. According to the survey, for patients with resectable LMGC without extrahepatic metastases, preoperative chemotherapy followed by resection of both primary (if still in place) and liver lesions was the preferred option for both the synchronous and the metachronous setting. For patients with unresectable LMGC, most of the sites recommended chemotherapy only. In this article, the detailed results of this survey are reported, shedding light on current community practice, and a joint EORTC-JCOG strategy of investigation is delineated.

A previous review published in 2008 highlighted the prognostic significance of baseline patient-reported outcomes (PROs) as independent predictors of the overall survival of patients with cancer in clinical studies. In response to the methodological limitations of studies included in the previous review, recommendations were subsequently published in the same year to promote a higher level of methodological rigour in studies of prognostic factors. Our systematic review aimed to provide an update on progress with the implementation of these recommendations and to assess whether the methodological quality of prognostic factor analyses has changed over time. Of the 44 studies published between 2006 and 2018 that were included in our review, more standardisation and rigour of the methods used for prognostic factor analysis was found compared with the previous review. 41 (93%) of the trials reported at least one PRO domain as independently prognostic. The most common significant prognostic factors reported were physical functioning (17 [39%] studies) and global health or quality of life (15 [34%] studies). These findings highlight the value of PROs as prognostic or stratification factors in research across most types of cancer.

Background: The importance of sex and gender as modulators of disease biology and treatment outcomes is well known in other disciplines of medicine, such as cardiology, but remains an undervalued issue in oncology. Considering the increasing evidence for their relevance, European Society for Medical Oncology decided to address this topic and organized a multidisciplinary workshop in Lausanne, Switzerland, on 30 November and 1 December 2018., Design: Twenty invited faculty members and 40 selected physicians/scientists participated. Relevant content was presented by faculty members on the basis of a literature review conducted by each speaker. Following a moderated consensus session, the final consensus statements are reported here., Results: Clinically relevant sex differences include tumour biology, immune system activity, body composition and drug disposition and effects. The main differences between male and female cells are sex chromosomes and the level of sexual hormones they are exposed to. They influence both local and systemic determinants of carcinogenesis. Their effect on carcinogenesis in non-reproductive organs is largely unknown. Recent evidence also suggests differences in tumour biology and molecular markers. Regarding body composition, the difference in metabolically active, fat-free body mass is one of the most prominent: in a man and a woman of equal weight and height, it accounts for 80% of the man's and 65% of the woman's body mass, and is not taken into account in body-surface area based dosing of chemotherapy., Conclusion: Sex differences in cancer biology and treatment deserve more attention and systematic investigation. Interventional clinical trials evaluating sex-specific dosing regimens are necessary to improve the balance between efficacy and toxicity for drugs with significant pharmacokinetic differences. Especially in diseases or disease subgroups with significant differences in epidemiology or outcomes, men and women with non-sex-related cancers should be considered as biologically distinct groups of patients, for whom specific treatment approaches merit consideration.

OBJECTIVES: This prospective multicenter cohort study aimed to describe new cancer events in nursing home residents (NHR). MATERIALS AND METHODS: The study was performed in 39 nursing homes from the Armonea network in Belgium, covering 4262 nursing home beds. All NHR in these homes were prospectively followed during 1 year for occurrence of cancer events (diagnosis or clinical suspicion of a new cancer or progression of a known cancer). After training, each site's local staff identified NHR with cancer events in collaboration with the treating general practitioner (GP). NHR with cancer events were included after informed consent, and data about general health and cancer status were collected every 3 months up to 2 years. RESULTS: In only nine NHR (median age 87 years, range 72-92), a cancer event was recorded during follow-up including five new (suspected or diagnosed) cancer events (incidence rate = 123/100.000 NHR per year) and four NHR with (suspected or diagnosed) progressive disease. In four NHR with suspected cancer, no diagnostic procedure was performed, and in five no anticancer treatment was started. CONCLUSION: Clinically relevant cancer events (potentially requiring diagnostic or therapeutic action) occur at a much lower frequency in NHR than expected from cancer incidence data in the general older population. Although some underreporting of cancer events cannot be excluded, this prospective study supports several previous retrospective observations that cancer events are rare in very frail older persons. Moreover, diagnostic and therapeutic actions for (suspected) cancer events are often not undertaken in this population. ispartof: JOURNAL OF GERIATRIC ONCOLOGY vol:10 issue:5 pages:805-810 ispartof: location:Netherlands status: published

10–20% of patients with gastric cancer (GC) have HER2+ tumors. Addition of trastuzumab (T) to cisplatin/fluoropyrimidine-based chemotherapy (CT) improved survival in metastatic, HER2+ GC. When pertuzumab (P) was added to neoadjuvant T and CT, a significant increase in histopathological complete response rate was observed in HER2+ breast cancer. This study aims to investigate the added benefit of using both HER2 targeting drugs (T alone or the combination of T + P), in combination with perioperative CT for localized HER2+ GC. This is a prospective, randomized, open-label, phase II trial. HER2 status from patients with resectable GC (UICC TNM7 tumor stage Ib-III) will be centrally determined. Two hundred and-fifteen patients from 52 sites in 14 countries will be centrally randomized (1:2:2 ratio) to one of the following treatment arms: 1. Standard: CT alone. CT regimens will be FLOT (5-FU, leucovorin, oxaliplatin, taxotere) CapOx (capecitabine, oxaliplatin) or FOLFOX (5-FU, leucovorin, oxaliplatin) according to investigator’s choice in Europe, and cisplatin/capecitabine in Asia. 2. Experimental arm 1: CT as in control group, plus T (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) at day 1, independent of CT chosen for 3 cycles of 3 weeks before and after surgery. 3. Experimental arm 2: CT plus T as in experimental arm 1, plus P (840 mg every 3 weeks) on day 1. Standard: CT alone. CT regimens will be FLOT (5-FU, leucovorin, oxaliplatin, taxotere) CapOx (capecitabine, oxaliplatin) or FOLFOX (5-FU, leucovorin, oxaliplatin) according to investigator’s choice in Europe, and cisplatin/capecitabine in Asia. Experimental arm 1: CT as in control group, plus T (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) at day 1, independent of CT chosen for 3 cycles of 3 weeks before and after surgery. Experimental arm 2: CT plus T as in experimental arm 1, plus P (840 mg every 3 weeks) on day 1. Adjuvant treatment with T or T + P will continue for 17 cycles in total. Stratification factors are: histology (intestinal/non-intestinal); region (Asia vs Europe); location (GEJ vs non-GEJ); HER2 immunohistochemistry score (IHC 3+ vs IHC 2+/FISH+) and chemotherapy regimen. Primary objective is to detect an increase in the major pathological response rate from 25 to 45% either with CT plus T alone, or with CT plus the combination of T and P. Depending on the results of the INNOVATION trial, the addition of HER2 targeted treatment with either T or T and P to CT may inform future study designs or become a standard in the perioperative management HER2+ GC. This article reports a health care intervention on human participants and was registered on July 10, 2014 under ClinicalTrials.gov identifier: NCT02205047 ; EudraCT: 2014–000722-38.

The aim of this manuscript is to discuss the viewpoint of the European Organisation for Research and Treatment of Cancer (EORTC) Gastric Cancer Taskforce and Japan Clinical Oncology Group (JCOG) Gastric Cancer Study Group on the current challenges in the multidisciplinary management of stage II-III gastric and gastro-oesophageal junction (GEJ) cancer. We seek to outline how these challenges are addressed in current trials of both groups. Key elements of future trials of EORTC and JCOG in this indication are described, and a joint vision on how multidisciplinary research of gastric and GEJ cancer patients should be organised is outlined. ispartof: EUROPEAN JOURNAL OF CANCER vol:124 pages:67-76 ispartof: location:England status: published

There is a great need to better design clinical trials that could improve patient outcomes and expedite drug development timelines. An understanding of general principles of classical clinical trial design and a consideration of innovative approaches and the concept of precision medicine carry great significance in that regard. It is important to keep in mind both the advantages and the pitfalls of different approaches, to maintain scientific rigor, and to always put patients first while improving how we conduct clinical trials.

The challenges of conducting surgical oncology trials have resulted to low quantity and poor quality research [1,2]. Considering the definitive role of surgery to offer cure, immediate response to improve surgical research is needed [3]. The European Organization for Research and Treatment of Cancer (EORTC) and the European Society of Surgical Oncology (ESSO) share the vision to achieve excellent surgical research and care for cancer patients. Building on their complimentary expertise, they embarked on a pilot project to map out challenges and initiate a sustainable collaboration to advance cancer surgery research in Europe. This pilot project is EORTC-ESSO 1409 GITCG/ ESSO-01: A Prospective Colorectal Liver Metastasis Database with an Integrated Quality Assurance Program (CLIMB). This article will describe the challenges, milestones and vision of both organizations in setting up this collaboration.

TPS4156 Background: Gastroesophageal adenocarcinoma (GEA) patients with metastatic lymph nodes (ypN+) or a microscopically incomplete surgical resection (R1) following neoadjuvant chemotherapy are at high risk of disease recurrence. Current practice is to continue with the same perioperative chemotherapy used prior to surgery, despite these suboptimal outcomes. Adjuvant immunotherapy with nivolumab has shown efficacy in poor risk GEA patients following chemoradiotherapy and surgery in the CheckMate 577 trial, and nivolumab and ipilimumab have demonstrated activity in advanced GEA. We hypothesise that high risk (ypN+ and/or R1) post resection GEA patients who are treated with nivolumab and ipilimumab will have better disease free survival than patients who continue with standard post-operative chemotherapy. Methods: VESTIGE is an ongoing, international, open label randomized phase II study designed to evaluate the efficacy of adjuvant nivolumab plus ipilimumab versus standard post-operative chemotherapy in high risk (ypN+ and/or R1) post resection GEA patients. Eligible patients (n=240) will be randomised 1:1 to receive post-operative adjuvant chemotherapy (identical regimen as pre-operatively) or nivolumab 3mg/kg IV q2w plus ipilimumab 1mg/kg IV q6w x 1 year. Key inclusion criteria include ypN+ and/or R1 status following neoadjuvant chemotherapy plus surgery and an adequate pre-specified surgical resection. The primary endpoint of the study is disease free survival, with secondary endpoints of overall survival, safety, toxicity and quality of life. Since start of recruitment in August 2019, the trial has recruited 85 of 240 patients at 18 sites in the Czech Republic, France, Germany, Israel, Italy, Norway, Poland, Spain, and United Kingdom. The VESTIGE translational research programme includes collection of pre-treatment biopsies, post-chemotherapy resection specimens and serial liquid biopsy on treatment to explore biomarkers predictive of immune checkpoint blockade efficacy. Clinical trial information: NCT03443856.

4067 Background: Defining the optimal neoadjuvant treatment for resectable locally advanced esophageal carcinoma remains an open question. The debate is fuelled by the fact that most of the available randomized clinical trials (RCT) accrued two histological subtypes (adenocarcinoma (AC) and squamous cell carcinoma (SCC)) and two anatomical locations (TE and GEJ). The aim of this individual patient data (IPD) meta-analysis was to investigate the effect of preoperative chemotherapy on survival with a specific focus on histological subtypes and anatomical locations. Methods: Were eligible published or unpublished RCT closed to accrual before December 2015 and comparing neoadjuvant chemotherapy (CS) to primary surgery (S), identified by electronic database, conference proceedings and clinical trial register. All analyses were conducted on IPD obtained from trial Investigators. The Primary endpoint was overall survival (OS), Secondary endpoints were disease-free survival (DFS) with a 6-months landmark time, local/distant relapse/death without relapse as competing events. Two subgroup analyses were pre-planned one on the histological subtype and another on the anatomical location. A stratified logrank test was used for OS and DFS, and a stratified fine and gray model for competing events. HR, and risk ratios (RR) were combined using a random effect model. Results: IPD were obtained from 12 RCT (2601 patients) out of 16 identified (2863 patients) When compared to S, CS was associated with a significantly increased OS, (HR = 0.85[0.78-0.92], p < 0.0001), with a 5-year absolute OS benefit of 5.7%. However, the subgroup analysis by histological subtype showed an OS benefit from CS higher for AC (HR = 0.80[0.72-0.91], p < 0.01), when compared to SCC (HR = 0.90[0.80-1.01], p = 0.06), but with p for interaction = 0.2. In the subgroup analysis by anatomical location CS benefit was seen across both anatomical location with a trend in favor of GEJ (TE: HR = 0.89[0.81-0.98], p = 0.02 GEJ: HR = 0.71[0.57-0.88]), p < 0.01, p for interaction = 0.057). CS also improved DFS (HR = 0.81[0.74-0.88], p < 0.0001), with the same trend for the subgroup analyses, with apparent significant benefit for AC HR = 0.80[0.72-0.91] when compared to SCC HR = 0.90[0.80-1.01], (p for interaction 0.045) and a similar benefit for both location (TE: HR = 0.89[0.81-0.98] p < 0.01, GEJ: HR = 0.71[0.57-0.88], p = 0.095, P for interaction 0.11). Local (HR = 0.76[0.63-0.92], p = 0.0045) and distant (HR = 0.87[0.76-0.99], p = 0.04) relapses were also significantly lower in the CS arm, with no significant variation according to histological subtypes or tumor location. Conclusions: Neoadjuvant chemotherapy significantly improves OS when added to upfront surgery and was equally effective in AC and SCC. A slightly more pronounced effect was observed for overall survival in the GEJ location vs. the TE.

The new therapeutic approach of using immune checkpoint inhibitors as anticancer agents is a landmark innovation. Early studies suggest that immune checkpoint inhibition might also be effective in patients with gastrointestinal cancer. To improve the efficacy of immunotherapy, different strategies are currently under evaluation. This review summarises the discussion during the European Organisation for Research and Treatment of Cancer Gastrointestinal Tract Cancer Translational Research Meeting in Mainz in November 2014 and provides an update on the most recent results of immune therapy in gastrointestinal cancers. Knowledge of potential relationships between tumour cells and their microenvironment including the immune system will be essential in gastrointestinal malignancies. In this context, the density of T cell infiltration within colorectal cancer metastases has been associated with response to chemotherapy, and a high expression of programmed cell death ligand 1 (PD-L1) in advanced gastric cancer has been related with poor prognosis. Effective targets might include neo-antigens encoded from genes carrying tumour-specific somatic mutations. Tailored immunotherapy based on such mutations could enable the effective targeting of an individual patient's tumour with vaccines produced on demand. Other strategies considering checkpoint inhibitors have shown efficacy by targeting cytotoxic T-lymphocyte-associated protein 4 and PD-1 or PD-L1. DNA mismatch repair-deficient tumours appear to be potentially the best candidates for these therapies. Finally, the combination of oncolytic viruses with immunotherapy might boost antitumour activity as well. Further evaluation of these promising immunological therapeutic approaches will require large prospective clinical studies.

This secondary analysis of the PETACC-3 trial examines the association of sex with incidence and severity of chemotherapy-related toxic effects in patients with stage II and III colorectal cancer treated with fluorouracil and leucovorin with or without irinotecan hydrochloride.

Background: Dose reduction in obese cancer patients has been replaced by fully weight-based dosing recommendations. No data, however, are available on the effects of dose reduction in obese stage III colon cancer patients undergoing adjuvant chemotherapy. Methods: Survival outcomes and toxicity data of obese (body mass index [BMI] >= 30 kg/m(2)), stage III colon cancer patients treated within the phase III PETACC 3 trial comparing leucovorin, 5-FU (LV5FU2) with LV5FU2 plus irinotecan were analysed retrospectively according to chemotherapy dosing at first infusion (i.e. fully weight-based dosed - versus dose-reduced group). Multivariate analyses on relapse free survival (RFS) and overall survival (OS) were conducted to adjust for baseline prognostic factors using Cox regression model. Results: 13.4% (280 of 2094 patients) had a BMI >= 30 kg/m(2), and 5.3% had both a BMI >= 30 kg/m(2) and a body surface area (BSA) >= 2 m(2). Dose reductions occurred in 16.1% of patients with a BMI >= 30 kg/m(2) and 32.4% with BMI >= 30 kg/m(2) and BSA >= 2 m(2), respectively. In patients with BMI >= 30 kg/m(2), multivariate analysis demonstrated a trend towards better RFS in the fully dosed compared to the dose-reduced group (Hazard ratio (HR): 0.69, 95% CI: 0.43-1.09; p = 0.11); however, there was no statistically significant difference in OS. In patients with BMI > 30 kg/m(2) and BSA > 2 m(2), multivariate analysis demonstrated better RFS in fully dosed compared with dose-reduced patients (HR: 0.48, 95% CI: 0.27-0.85; p = 0.01) and a strong trend towards better OS (HR: 0.53, 95% CI: 0.28-1.01; p = 0.052). This group comprised predominantly of men. Conclusions: Data support the recommendation of using fully dosed chemotherapy for the adjuvant treatment in obese patients with colon cancer. (C) 2018 Elsevier Ltd. All rights reserved.

Several phase I/II studies of chemoradiotherapy for gastric cancer have reported promising results, but the significance of preoperative radiotherapy in addition to chemotherapy has not been proven. In this study, a systematic literature search was performed to capture survival and postoperative morbidity and mortality data in randomised clinical studies comparing preoperative (chemo)radiotherapy or chemotherapy versus surgery alone, or preoperative chemoradiotherapy versus chemotherapy for gastric and/or gastro-oesophageal junction (GOJ) cancer. Hazard ratios (HRs) for overall mortality were extracted from the original studies, individual patient data provided from the principal investigators of eligible studies or the earlier published meta-analysis. The incidences of postoperative morbidities and mortalities were also analysed. In total 18 studies were eligible and data were available from 14 of these. The meta-analysis on overall survival yielded HRs of 0.75 (95% CI 0.65–0.86, P < 0.001) for preoperative (chemo)radiotherapy and 0.83 (95% CI 0.67–1.01, P = 0.065) for preoperative chemotherapy when compared to surgery alone. Direct comparison between preoperative chemoradiotherapy and chemotherapy resulted in an HR of 0.71 (95% CI 0.45–1.12, P = 0.146). Combination of direct and adjusted indirect comparisons yielded an HR of 0.86 (95% CI 0.69–1.07, P = 0.171). No statistically significant differences were seen in the risk for postoperative morbidity or mortality between preoperative treatments and surgery alone, or preoperative (chemo)radiotherapy and chemotherapy. Preoperative (chemo)radiotherapy for gastric and GOJ cancer showed significant survival benefit over surgery alone. In comparisons between preoperative chemotherapy and (chemo)radiotherapy, there is a trend towards improved survival when adding radiotherapy, without increased postoperative morbidity or mortality.

A popular choice when analyzing ordinal data is to consider the cumulative proportional odds model to relate the marginal probabilities of the ordinal outcome to a set of covariates. However, application of this model relies on the condition of identical cumulative odds ratios across the cut-offs of the ordinal outcome; the well-known proportional odds assumption. This paper focuses on the assessment of this assumption while accounting for repeated and missing data. In this respect, we develop a statistical method built on multiple imputation (MI)based on generalized estimating equations that allows to test the proportionality assumption under the missing at random setting. The performance of the proposed method is evaluated for two MI algorithms for incomplete longitudinal ordinal data. The impact of both MI methods is compared with respect to the type I error rate and the power for situations covering various numbers of categories of the ordinal outcome, sample sizes, rates of missingness, well-balanced and skewed data. The comparison of both MI methods with the complete-case analysis is also provided. We illustrate the use of the proposed methods on a quality of life data from a cancer clinical trial.

International audience; BACKGROUND:Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer.METHODS:Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9).RESULTS:For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items.CONCLUSION:The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer.

In cancer clinical trials, health-related quality of life (HRQoL) is a major outcome measure. It is generally assessed at specified time intervals by filling out a questionnaire with ordered response categories. Despite recent advances in the statistical methodology for handling ordinal longitudinal outcome data, most users keep treating HRQoL scales as continuous rather than ordinal variables regardless of the number of categories. The purpose of this study was to compare the results of analyzing HRQoL longitudinal data under both approaches, continuous and ordinal. The EORTC QLQ-C30 scores of two EORTC randomized brain cancer clinical trials (26951 and 26981) were analyzed using the two approaches. In the 26951 trial, a total of 368 patients were randomly assigned to receive either radiotherapy (RT) or the same RT plus procarbazine, CCNU, and vincristine. In the 26981 trial, 573 patients were randomly allocated to RT or RT plus temozolomide. Comparison of the two treatment arms was done using methods for longitudinal quantitative and longitudinal ordinal data. Both statistical methods were adapted to account for missing data and compared in terms of statistical significance of the results (p values) but also with respect to data interpretation. Three scales, i.e., appetite loss, insomnia, and drowsiness, presenting four response categories ("Not at all", "A little", "Quite a bite", and "Very much") were analyzed in each trial. Both statistical methods (continuous and ordinal) showed statistically significant differences between the two treatments, not only globally but also at the same assessment time points. The magnitude of the p values, however, varied at some time points and was less pronounced in the ordinal approach. The analysis of the two clinical trials showed that treating the HRQoL scales by a quantitative or an ordinal method did not make much difference as far as statistical significance was concerned. The interpretation of results, however, was easier under the ordinal approach. Treatment effects may be more meaningful when expressed in terms of odds ratios than as mean values, particularly when the number categories is small.

Aim The aim of this study is to describe local tumour control after radiofrequency ablation (RFA) and surgical resection (RES) of colorectal liver metastases (CLM) in two independent European Organisations for Research and Treatment of Cancer (EORTC) studies. Background Only 10–20% of patients with newly diagnosed CLM are eligible for curative RES. RFA has found a place in daily practice for unresectable CLM. There are no prospective trials comparing RFA to RES for resectable CLM. Methods The CLOCC trial randomised 119 patients with unresectable CLM between RFA (±RES) + adjuvant FOLFOX (±bevacizumab) versus FOLFOX (±bevacizumab) alone. The EPOC trial randomised 364 patients with resectable CLM between RES ± perioperative FOLFOX. We describe the local control of resected patients with lesions ⩽4 cm in the perioperative chemotherapy arm of the EPOC trial (N = 81) and the RFA arm of the CLOCC trial (N = 55). Results Local recurrence (LR) rate for RES was 7.4% per patient and 5.5% per lesion. LR rate for RFA was 14.5% per patient and 6.0% per lesion. When lesion size was limited to 30 mm, LR rate for RFA lesions was 2.9% per lesion. Non-local hepatic recurrences were more often observed in RFA patients than in RES patients, 30.9% and 22.3% respectively. Patients receiving RFA had a more advanced disease. Conclusions LR rate after RFA for lesions with a limited size is low. The local control per lesion does not appear to differ greatly between RFA and surgical resection. This study supports the local control of RFA in patients with limited liver metastases. Future studies should evaluate in which patients RFA could be an equal alternative to liver resection

Background: Tumor ablation is often employed for unresectable colorectal liver metastases. However, no survival benefit has ever been demonstrated in prospective randomized studies. Here, we investigate the long-term benefits of such an aggressive approach. Methods: In this randomized phase II trial, 119 patients with unresectable colorectal liver metastases (n 38%) was met. We now report on long-term OS results. All statistical tests were two-sided. The analyses were according to intention to treat. Results: At a median follow up of 9.7 years, 92 of 119 (77.3%) patients had died: 39 of 60 (65.0%) in the combined modality arm and 53 of 59 (89.8%) in the systemic treatment arm. Almost all patients died of progressive disease (35 patients in the combined modality arm, 49 patients in the systemic treatment arm). There was a statistically significant difference in OS in favor of the combined modality arm (hazard ratio [HR] = 0.58, 95% confidence interval [CI] = 0.38 to 0.88, P = .01). Three-, five-, and eight-year OS were 56.9% (95% CI = 43.3% to 68.5%), 43.1% (95% CI = 30.3% to 55.3%), 35.9% (95% CI = 23.8% to 48.2%), respectively, in the combined modality arm and 55.2% (95% CI = 41.6% to 66.9%), 30.3% (95% CI = 19.0% to 42.4%), 8.9% (95% CI = 3.3% to 18.1%), respectively, in the systemic treatment arm. Median OS was 45.6 months (95% CI = 30.3 to 67.8 months) in the combined modality arm vs 40.5 months (95% CI = 27.5 to 47.7 months) in the systemic treatment arm. Conclusions: This phase II trial is the first randomized study demonstrating that aggressive local treatment can prolong OS in patients with unresectable colorectal liver metastases.

Since the creation of the EORTC Headquarters in 1974, major advances have been made in the methodology used in the design and analysis of cancer clinical trials. However, the speed of these developments in the fields of biology, medicine, and statistics has greatly increased since the turn of the 21st century. These changes have all become possible because of the increased computer power now available. The landscape of therapeutic anti-cancer development changed completely with the advent of the so-called “targeted agents” that treat the underlying molecular basis of the disease rather than the symptoms of tumor proliferation. The new challenges posed by the clinical development of these numerous new agents that are expected to work in often yet-to-be-identified subgroups of patients induced a new wave of methodological developments. Some of these were readily embraced by the EORTC Headquarters statistics department, while others met with opposition. Our assessment is still in progress in many areas. Trials tend to become increasingly complex so that their planning relies on an increasing number of unknown parameters that need to be monitored during the trial itself, one development being “adaptive” design methodology. Because the knowledge required to design these new and more complex clinical trials and associated research program spans more disciplines (biology, genomics, radiology) and involves specialized knowledge within those disciplines, continued success requires further developing our partnerships with specialized departments (imaging, bio-informatics, biology, etc.) within EORTC Headquarters and in EORTC affiliated centers as well as collaborations with specialized statisticians from academia.

During the last decades, the evolution of treatment - including radiotherapy, chemotherapy and targeted agents - has improved the cure and survival of patients with gastrointestinal (GI) cancer. Within the past 50 years of the EORTC's existence, significant progress has been made in the fight against cancer. During this time several cancer clinical trials were completed, and through these we are able to identify the most notable advances in GI cancer research done by the EORTC Gastrointestinal Tract Cancer Group (GI Group). Several EORTC clinical trials results have changed practice (e.g. standard of care of liver metastases of colorectal cancer has been changed by the EPOC trial) or have helped to support new treatment strategies in either early- or advanced-stage GI cancers. In addition to its clinical activities the group has started an extensive program of translational research. This changed strategy towards a translational, multidisciplinary program regarded as the basis for future developments. This review of the major achievements of the GI Group shows that it has played an important role in the scientific development of the understanding and treatment of GI cancer over the last 50 years. © 2012 European Organisation for Research and Treatment of Cancer., SCOPUS: ar.j, info:eu-repo/semantics/published

3500Background: The PETACC-6 trial investigated the role of oxaliplatin in combination with preoperative capecitabine-based chemoradiation (CRT) and postoperative capecitabine (CT) to improve disea...

3558Background: The European Organization for Research & Treatment of Cancer & European Society of Surgical Oncology joined forces to build an infrastructure for surgical quality assurance (QA) in ...

AimsThe psychometric properties of the EORTC QLQ-BN20, a brain cancer-specific HRQOL questionnaire, have been previously determined in an English-speaking sample of patients. This study examined the validity and reliability of the questionnaire in a multi-national, multi-lingual study.MethodsQLQ-BN20 data were selected from two completed phase III EORTC/NCIC clinical trials in brain cancer (N = 891), including 12 languages. Experimental treatments were surgery followed by radiotherapy (RT) and adjuvant PCV chemotherapy or surgery followed by concomitant RT plus temozolomide (TMZ) chemotherapy and adjuvant TMZ chemotherapy. Standard treatment consisted of surgery and postoperative RT alone. The psychometrics of the QLQ-BN20 were examined by means of multi-trait scaling analyses, reliability estimation, known groups validity testing, and responsiveness analysis.ResultsAll QLQ-BN20 items correlated more strongly with their own scale (r > 0.70) than with other QLQ-BN20 scales. Internal consistency reliability coefficients were high (all α 0.70). Known-groups comparisons yielded positive results, with the QLQ-BN20 distinguishing between patients with differing levels of performance status and mental functioning. Responsiveness of the questionnaire to changes over time was acceptable.ConclusionThe QLQ-BN20 demonstrates adequate psychometric properties and can be recommended for use in conjunction with the QLQ-C30 in assessing the HRQOL of brain cancer patients in international studies.

Purpose Prophylactic cranial irradiation (PCI) in patients with extensive-disease small-cell lung cancer (ED-SCLC) leads to significantly fewer symptomatic brain metastases and improved survival. Detailed effects of PCI on health-related quality of life (HRQOL) are reported here. Patients and Methods Patients (age, 18 to 75 years; WHO ≤ 2) with ED-SCLC, and any response to chemotherapy, were randomly assigned to either observation or PCI. Health-related quality of life (HRQOL) and patient-reported symptoms were secondary end points. The European Organisation for the Research and Treatment of Cancer core HRQOL tool (Quality of Life Questionnaire C30) and brain module (Quality of Life Questionnaire Brain Cancer Module) were used to collect self-reported patient data. Six HRQOL scales were selected as primary HRQOL end points: global health status; hair loss; fatigue; and role, cognitive and emotional functioning. Assessments were performed at random assignment, 6 weeks, 3 months, and then 3-monthly up to 1 year and 6-monthly thereafter. Results Compliance with the HRQOL assessment was 93.7% at baseline and dropped to 60% at 6 weeks. Short-term results up to 3 months showed that there was a negative impact of PCI on selected HRQOL scales. The largest mean difference between the two arms was observed for fatigue and hair loss. The impact of PCI on global health status as well as on functioning scores was more limited. For global health status, the observed mean difference was eight points on a scale 0 to 100 at 6 weeks (P = .018) and 3 months (P = .055). Conclusion PCI should be offered to all responding ED SCLC patients. Patients should be informed of the potential adverse effects from PCI. Clinicians should be alert to these; monitor their patients; and offer appropriate support, clinical, and psychosocial care.

A significant body of research exists in oncology to identify and evaluate prognostic factors, historically focused on histology, clinical stage and laboratory parameters. Recent evidence suggests that patient self-reported health-related quality-of-life (HRQOL) data provide additional prognostic information. A review by Gotay et al. of published prognostic analyses reports on the usefulness of patient-reported outcomes (PROs), including HRQOL, in predicting survival in cancer patients in clinical trials. An impressive number of studies have found a positive relationship that supports an independent association between HRQOL and survival. However, due to the considerable diversity in, for example, patient groups, types of HRQOL measures used and analytical strategies, current evidence is far from conclusive. This paper examines the statistical research methods employed, discusses key issues for HRQOL prognostic factor-analysis parameters and proposes recommendations for future outcome research.