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Background: The standard of care for the treatment of locally advanced rectal cancer (LARC) results in an excellent local disease control but the metastasis rates remain high. PRODIGE 23 demonstrated improved disease-free survival (DFS) and metastasis-free survival (MFS) with total neoadjuvant therapy versus standard of care in this population. Long-term analysis of overall survival (OS) is reported here., Patients and Methods: The study design, participants, and primary endpoint DFS have been reported for this multicenter, randomized, open-label, phase III trial investigating the neoadjuvant chemotherapy with mFOLFIRINOX (6 cycles) followed by chemoradiotherapy, surgery, and adjuvant chemotherapy (6 cycles), versus chemoradiotherapy, surgery, and adjuvant chemotherapy (12 cycles) in patients with locally advanced rectal adenocarcinoma under peritoneal reflection on magnetic resonance imaging, and staged cT3/T4. Key secondary endpoints included OS, MFS, and local and metastatic recurrence rate., Results: With a median follow-up of 82.2 months, the 7-year DFS was 67.6% [95% confidence interval (CI) 60.7% to 73.9%] and 62.5% (95% CI 55.6% to 68.6%) [restricted mean survival time (RMST) difference 5.73 months, 95% CI 0.05-11.41 months, P = 0.048] in the neoadjuvant chemotherapy and the standard-of-care groups, respectively. The 7-year MFS was 79.2% (95% CI 73.0% to 84.4%) in the neoadjuvant chemotherapy group and 72.3% (95% CI 65.8% to 77.8%) in the standard-of-care group (RMST difference 6.1 months, 95% CI 0.93-11.37 months, P = 0.021). The 7-year OS was 81.9% (95% CI 75.8% to 86.6%) in the neoadjuvant chemotherapy group and 76.1% (95% CI 69.7% to 81.2%) in the standard-of-care group (RMST difference 4.37 months, 95% CI 0.35-8.38 months, P = 0.033). The safety profile remained unchanged since the previous analysis., Conclusions: Neoadjuvant chemotherapy with mFOLFIRINOX followed by chemoradiotherapy improved OS, confirmed long-term DFS and MFS benefits in LARC patients, and should be considered as one of the best options of care for these patients., (Copyright © 2024 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

Background: After surgical resection of pancreatic ductal adenocarcinoma (PDAC), patients are predominantly treated with adjuvant chemotherapy, commonly consisting of gemcitabine (GEM)-based regimens or the modified FOLFIRINOX (mFFX) regimen. While mFFX regimen has been shown to be more effective than GEM-based regimens, it is also associated with higher toxicity. Current treatment decisions are based on patient performance status rather than on the molecular characteristics of the tumor. To address this gap, the goal of this study was to develop drug-specific transcriptomic signatures for personalized chemotherapy treatment., Patients and Methods: We used PDAC datasets from preclinical models, encompassing chemotherapy response profiles for the mFFX regimen components. From them we identified specific gene transcripts associated with chemotherapy response. Three transcriptomic artificial intelligence signatures were obtained by combining independent component analysis and the least absolute shrinkage and selection operator-random forest approach. We integrated a previously developed GEM signature with three newly developed ones. The machine learning strategy employed to enhance these signatures incorporates transcriptomic features from the tumor microenvironment, leading to the development of the 'Pancreas-View' tool ultimately clinically validated in a cohort of 343 patients from the PRODIGE-24/CCTG PA6 trial., Results: Patients who were predicted to be sensitive to the administered drugs (n = 164; 47.8%) had longer disease-free survival (DFS) than the other patients. The median DFS in the mFFX-sensitive group treated with mFFX was 50.0 months [stratified hazard ratio (HR) 0.31, 95% confidence interval (CI) 0.21-0.44, P < 0.001] and 33.7 months (stratified HR 0.40, 95% CI 0.17-0.59, P < 0.001) in the GEM-sensitive group when treated with GEM. Comparatively patients with signature predictions unmatched with the treatments (n = 86; 25.1%) or those resistant to all drugs (n = 93; 27.1%) had shorter DFS (10.6 and 10.8 months, respectively)., Conclusions: This study presents a transcriptome-based tool that was developed using preclinical models and machine learning to accurately predict sensitivity to mFFX and GEM., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Objectives: Appropriate use of palliative systemic treatments near end-of-life is crucial to reduce aggressiveness of cancer care. The study's objective is to evaluate cancer quality-of-care near end-of-life in our cancer institute., Methods: From a retrospective cohort, we included all adults with metastatic solid cancers who died in 2019. The use of palliative systemic treatments close to death was measured from quality-of-care indicators described by Earle and al. The integration of supportive care into standard oncology care was also evaluated. All the information were collected from electronic records., Results: Of the 452 patients, 6.2% received systemic treatment in the last 14 days of life and 8.4% started a new systemic treatment in the last 30 days of life. Eighty six percent met a supportive care physician. This intervention was significantly less frequent in the TS ≤14 group than in the TS >30 group (71.4 % vs 89.5 % p=0.021). The main reasons for first contact were pain (35 %), early palliative care (29 %) and then exclusive palliative care (17.5 %)., Conclusion: Our institute offers a good quality of end-of-life care for patients with metastatic solid cancers. However, improvements should be done regarding prognostic estimation and integration of palliative care., (Copyright © 2022 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background and Objectives: We have previously showed that for patients with wild-type RAS metastatic colorectal cancer (mCRC) progressing after bevacizumab plus chemotherapy, bevacizumab continuation plus a switch of chemotherapy is the most appropriate option (PRODIGE 18 phase II study). Here we aimed to determine treatment impact in patient's Health-Related Quality Of Life (HRQoL) in PRODIGE18 study., Methods: HRQoL was evaluated in 2 arms bevacizumab or cetuximab-combined with chemotherapy (modified FOLFOX6 [mFOLFOX6] or FOLFIRI) using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 at baseline, first and third tumor evaluation and at the end of the study. The temporal evolution of quality of life scores was investigated using longitudinal linear mixed models of variance. The time until definitive deterioration (TUDD) was estimated using the Kaplan-Meier method and the long-rank test. A univariate Cox model was used to calculate HR with 95% CI. A multivariate Cox model was applied to determine association of TUDD with age and gender. Safety was assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events., Results: HRQoL QLQ-C30 questionnaire compliance was high at baseline (>90%) and declined over time (∼70% in tumor evaluation 1 and ∼ 60% in tumor evaluation 3), but remained similar in both treatment arms. Patient reported mean diarrhea QLQ-C30 score is significantly higher in bevacizumab treatment arm. Clinician reported mild diarrhea was more frequently declared in bevacizumab treatment arm. Cox multivariate analyses showed no statistically significant differences in TUDD for all QLQ-C30 scales between treatments. TUDD of appetite loss was significantly associated to age., Conclusions: Our study shows that no relevant impairment of patients HRQoL between the 2 treatment arms. So, the analysis of the HRQoL with equal effectiveness does not make it possible to favor one treatment over another., Competing Interests: Disclosure Dr Bouché reported serving as a consultant for Roche, Amgen, Merck Sereno, and Bayer and participating in speakers bureaus for Pierre Fabre and Servier. Dr François reported receiving honoraria from Merck Serono, Roche, Amgen, Lilly, Servier, and Sanofi. Dr Artru reported receiving honoraria from Roche, Merck Serono, Amgen, Servier, Bayer, Sanofi, Lilly, and Celgene. Dr Adenis reported receiving honoraria from Roche, Sanofi, Bayer, and Amgen and receiving grants from Sanofi and Bayer. Dr Borg reported receiving honoraria from Roche and Servier and receiving grants from Roche. Dr Bennouna reported receiving honoraria from Roche, Amgen, Boehringer-Ingelheim, AstraZeneca, Bristol-Myers Squibb, and Bayer. No conflicts of interest were disclosed by the other authors., (Copyright © 2021. Published by Elsevier Inc.)

Background: The impact of the first coronavirus disease 2019 (COVID-19) wave on cancer patient management was measured within the nationwide network of the Unicancer comprehensive cancer centers in France., Patients and Methods: The number of patients diagnosed and treated within 17 of the 18 Unicancer centers was collected in 2020 and compared with that during the same periods between 2016 and 2019. Unicancer centers treat close to 20% of cancer patients in France yearly. The reduction in the number of patients attending the Unicancer centers was analyzed per regions and cancer types. The impact of delayed care on cancer-related deaths was calculated based on different hypotheses., Results: A 6.8% decrease in patients managed within Unicancer in the first 7 months of 2020 versus 2019 was observed. This reduction reached 21% during April and May, and was not compensated in June and July, nor later until November 2020. This reduction was observed only for newly diagnosed patients, while the clinical activity for previously diagnosed patients increased by 4% similar to previous years. The reduction was more pronounced in women, in breast and prostate cancers, and for patients without metastasis. Using an estimated hazard ratio of 1.06 per month of delay in diagnosis and treatment of new patients, we calculated that the delays observed in the 5-month period from March to July 2020 may result in an excess mortality due to cancer of 1000-6000 patients in coming years., Conclusions: In this study, the delays in cancer patient management were observed only for newly diagnosed patients, more frequently in women, for breast cancer, prostate cancer, and nonmetastatic cancers. These delays may result is an excess risk of cancer-related deaths in the coming years., Competing Interests: Disclosure JYB reports research support and honoraria from Troche, BMS, MSD, PharmaMar, Bayer, Deciphera, GSK, Novartis, and AstraZeneca. JPD reports institutional fees for advisory or speaker roles for Genentech, Roche, BMS, MSD, and Novartis, and institutional grants for research projects with Genentech, Roche, BMS, MSD, Debiopharm, and Astra Zeneca. JCS reports shares from AstraZeneca, Daiichi Sankyo, Gritstone, and is also a full-time employee of AstraZeneca from September 2017 to December 2019. All other authors have declared no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The European Organization for Research and Treatment of Cancer (EORTC) QLQ-BR23 was one of the first disease-specific questionnaires developed in 1996 to assess quality of life (QoL) in patients with breast cancer (BC). However, since 1996 major changes in BC treatment have occurred, requiring an update of the EORTC BC module. This study presents the results of the phase I-III update of the QLQ-BR23 questionnaire., Patients and Methods: The update of the EORTC QLQ-BR23 module followed standard EORTC guidelines. A systematic literature review revealed 83 potential relevant QoL issues during phases I and II. After shortening the issues list and following interviews with patients and health care providers, 15 relevant issues were transformed into 27 items. The preliminary module was pretested in an international, multicentre phase III study to identify and solve potential problems with wording comprehensibility and acceptability of the items. Descriptive statistics are provided. Analyses were qualitative and quantitative. We provide a psychometric structure of the items., Results: The phase I and II results indicated the need to supplement the original QLQ-BR23 with additional items related to newer therapeutic options. The phase III study recruited a total of 250 patients (from 12 countries). The final updated phase III module contains a total of 45 items: 23 items from the QLQ-BR23 and 22 new items. The new items contain two multi-item scales: a target symptom scale and a satisfaction scale. The target symptom scale can be divided into three subscales: endocrine therapy, endocrine sexual and skin/mucosa scale., Conclusion: Our work has led to the development of a new EORTC QLQ-BR45 module that provides a more accurate and comprehensive assessment of the impact of new and scalable treatments on patients' QoL. The final version of the EORTC QLQ-BR45 is currently available for use in clinical practice. The final phase IV study is underway to confirm psychometric properties of the module., (Copyright © 2019 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

Introduction: Cancer management is a public health issue in France. Its incidence is stabilizing even decreasing, but the prevalence increases. Public policies give at the general practitioner (GP) a central role in oncological care: it must be present at all stages of the disease, from screening to post-cancer., Methods: One-year prospective monocentric study in a cancer institute. Distribution of a questionnaire to unplanned hospitalized patients and collection of socio-demographic and medical data in their files., Results: Fifty-four percent of the study patients did not consult their GP for the health problem that motivated hospitalization. Sixty-nine percent of patients surveyed believe that GP is not the primary care physician for the management of complications and adverse effects of oncology treatments. A large majority of patients have metastatic cancer while only 40 % followed by the support care team., Discussion: GP's are not yet integrated into the active management of cancer for study patients. The symptoms that GP's say they can easily manage are the most frequent reasons for hospitalization., (Copyright © 2019. Published by Elsevier Masson SAS.)

Background: Recurrence and distant metastases remain a significant issue in locally advanced rectal cancer (LARC). Several multimodal strategies are assessed in clinical trials., Patients and Methods: Patients with mid/low magnetic resonance imaging-defined high-risk LARC were randomized to arm A (12-week bevacizumab + FOLFOX-4 then bevacizumab-5-fluorouracil [5-FU]-radiotherapy [RT] before total mesorectal excision [TME]) or arm B (bevacizumab-5-FU-RT then TME). Long-term efficacy and safety up to 5 years' follow-up are reported. No comparison between arms was planned., Results: Overall, 91 patients (46 in arm A and 45 in arm B) were included. Main results have been presented previously. During the late follow-up period (> 4 weeks after surgery), 4 patients (8.7%) in arm A and 4 (8.9%) in arm B experienced grade 3/4 adverse events related to bevacizumab; the most frequent were 2 anastomotic fistulas (both in arm A) and abscesses (1 in arm A and 2 in arm B). At 5 years' follow-up, 9 (19.6%) and 11 (24.4%) patients in arms A and B developed a fistula in the year after surgery, and 2 (4.3%) in arm A at > 1 year after surgery. Most resolved before study end. Five-year disease-free survival was 70% and 64.3% in arms A and B, respectively. Five-year overall survival was 90.5% (95% confidence interval, 76.7, 96.3) in arm A and 72.7% (95% confidence interval, 56.0, 83.9) in arm B., Conclusion: Neoadjuvant bevacizumab + FOLFOX-4 may have the potential to increase survival outcomes when followed by bevacizumab-5-FU-RT and TME in LARC. Bevacizumab-5-FU-RT then TME was associated with a higher-than-projected rate of anastomotic fistulas. Further research of neoadjuvant strategies in LARC is encouraged., (Copyright © 2019. Published by Elsevier Inc.)

Background: This document is a summary of the French intergroup guidelines regarding the management of pancreatic adenocarcinoma (PA), updated in July 2018., Design: This collaborative work was produced under the auspices of all French medical and surgical societies involved in the management of PA. It is based on the previous guidelines, recent literature review and expert opinions. Recommendations were graded in three categories, according to the level of evidence., Results: Over the last seven years, significant changes in PA management have been implemented in clinical practice. Imaging/staging: diffusion magnetic resonance imaging is useful before surgery to rule out small liver metastases., Surgery: centralization of pancreatic surgery in expert centers is associated with a decreased postoperative mortality. Adjuvant chemotherapy: modified FOLFIRINOX in fit patients, or gemcitabine, or 5-FU, or gemcitabine plus capecitabine, to be discussed on a case-by-case basis. Locally advanced PA: no survival benefit of chemoradiotherapy. Metastatic PA: FOLFIRINOX and gemcitabine plus nab-paclitaxel combination are first-line standards in fit patients; second-line with 5FU/nal-IRI or 5FU/oxaliplatin combination after first-line gemcitabine., Conclusion: Guidelines for management of PA are continuously evolving and need to be regularly updated. This constant progress is made possible through clinical and translational research. However, as each individual case is particular, they cannot substitute to multidisciplinary tumor board discussion., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Outcome of intermediate risk rectal cancer may be improved by the addition of oxaliplatin during 5-fluoruracil concomitant neoadjuvant chemoradiotherapy. The purpose of this study is to analyze the main clinical results of the ACCORD12 trial (NCT00227747) in rectal cancer after 5 years of follow-up., Patients and Methods: Inclusion criteria were as follows: rectal adenocarcinoma accessible to digital examination staged T3-T4 Nx M0 (or T2 Nx distal anterior rectum). Two neoadjuvant chemoradiotherapy regimens were randomized: CAP45 (RT 45 Gy + capecitabine) and CAPOX50 (RT 50 Gy + capecitabine and oxaliplatin). Main end point was sterilization of the operative specimen. Acute and late toxicities were prospectively analyzed with dedicated questionnaires., Results: Between November 2005 and July 2008, 598 patients were included in the trial. After a median follow-up of 60.2 months, there was no difference between treatment arms in multivariate analysis either for disease-free survival or overall survival (OS) [P = 0.9, hazard ratio (HR)=1.02; 95% confidence interval (CI), 0.76-1.36 and P = 0.3, HR = 0.87; 95% CI, 0.66-1.15, respectively]. There was also no difference of local control in univariate analysis (P = 0.7, HR = 0.92; 95% CI, 0.51-1.66). Late toxicities were acceptable with 1.6% G3 anal incontinence, and <1% G3 diarrhea, G3 rectal bleeding, G3 stenosis, G3-4 pain, G3 urinary incontinence, G3 urinary retention and G3 skeletal toxicity. There was a slight increase of erectile dysfunction over time with a 63% rate of erectile dysfunction at 5 years. There was no significant statistical difference for these toxicities between treatment arms., Conclusions: The CAPOX50 regimen did not improve local control, disease-free survival and overall survival in the ACCORD12 trial. Late toxicities did not differ between treatment arms., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Introduction: This document is a summary of the French Intergroup guidelines regarding the management of rectal adenocarcinoma published in February 2016., Method: This collaborative work, under the auspices of most of the French medical societies involved in the management of rectal cancer, is based on the previous guidelines published in 2013. Recommendations are graded into 3 categories according to the level of evidence of data found in the literature., Results: In agreement with the ESMO guidelines (2013), non-metastatic rectal cancers have been stratified in 4 risk groups according to endoscopy, MRI or endorectal-ultrasonography. Locally-advanced tumors are limited to groups 3 and 4 (T3≥4cm or T3c-d or N1-2 or T4). These tumors are usually treated using neoadjuvant treatment and total proctectomy (TME). Adjuvant treatment depends on the pathological findings. Very early (group 1) or early (group 2) tumors are managed mainly by surgery, and organ preservation may be an option in selected cases. For metastatic tumors, the recommendations are based on less robust evidence and chemotherapy plays a major role., Conclusion: Such recommendations are constantly being optimized and each individual case must be discussed within a Multi-Disciplinary Team., (Copyright © 2017. Published by Elsevier Ltd.)

Background: We performed a randomized, non-comparative phase II study evaluating docetaxel in combination with either daily continuous (protracted IV) 5-fluorouracil or cisplatin administered weekly, concurrent to radiotherapy in the treatment of locally advanced pancreatic carcinoma. Results of the docetaxel plus cisplatin regimen are reported., Methods: Forty chemotherapy-naive patients with locally advanced pancreatic carcinoma were randomly assigned to receive 5-fluorouracil and docetaxel or docetaxel 20mg/m(2) and cisplatin 20mg/m(2)/week, plus concurrent radiotherapy for 6 weeks. The radiation dose to the primary tumour was 54Gy in 30 fractions. The trial's primary endpoint was the 6-month crude non-progression rate., Results: 51 patients from 7 centres were included in the docetaxel-cisplatin treatment group. Six-month non-progression rate was 39% (95% confidence interval: 26-53). Median overall survival was 9.6 months (95% confidence interval: 2.4-60.7); 6 complete and 8 partial responses were obtained. Six patients survived more than 2 years after their inclusion in the trial. Grade ≥3 toxicity was reported in 63% of patients; no treatment-related death occurred. Severe toxicities were mainly anorexia (22%), vomiting (20%) and fatigue (24%)., Conclusions: Despite inadequate efficacy according to the main end point, this regimen gave a satisfactory rate of objective response (27%) with tolerable toxicity., (Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: The ACCORD 16 phase II trial aimed to evaluate the objective response rate after combination of conventional chemoradiotherapy (CRT) and cetuximab in locally advanced anal canal carcinoma (LAACC)., Patients and Methods: Immunocompetent patients with histologically confirmed LAACC received CRT [45 gray (Gy)] in 25 fractions over 5 weeks, fluorouracil and cisplatin during weeks 1 and 5), in combination with weekly dose of cetuximab (250 mg/m(2) with a loading dose of 400 mg/m(2) 1 week before irradiation), and a standard dose boost (20 Gy). The trial was originally designed to include 81 patients to detect a 15% of objective response increase with the new combination in comparison with CRT., Results: The trial was prematurely stopped after the declaration of 15 serious adverse events (SAEs) in 14 out of 16 patients. Five patients received the entire planned treatment, and the compliance was higher after amendments of the protocol. Among the 15 SAEs, 6 were unexpected. Grade (G) 3/4 acute toxic effects, observed in 88% patients, were general (n = 13, 81%), digestive (n = 9, 56%), dermatological (n = 5, 31%), infectious (n = 4, 25%), haematological (n = 3, 19%), and others (n = 9); and three patients suffered from six G3/4 late toxic effects. No treatment-related death was reported. All 11 assessable patients had an objective response consisting of six complete (55%) and five partial (45%) response 2 months after the end of the treatment. Thirteen patients were followed up with a median of 22 months [95% confidence interval (CI ): 18-27] and had a 1-year colostomy-free survival, progression-free and overall survival rate of 67% (95% CI: 40%-86%), 62% (95% CI: 36%-82%), and 92% (95% CI: 67%-99%), respectively., Conclusion: CRT plus cetuximab was unacceptably toxic in this population of patients. Results of others phase II trials evaluating this combination are awaited to confirm these findings., Eudra Ct No: 2007-007029-38.

Objectives: The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group is developing a computer-adaptive test (CAT) version of the EORTC Quality of Life Questionnaire (QLQ-C30). We evaluated the measurement properties of the CAT versions of physical functioning (PF) and fatigue (FA) and compared these with the corresponding QLQ-C30 scales., Study Design and Setting: Based on international samples of more than 1,000 cancer patients, we simulated CAT administration of varying numbers of items and compared the resulting scores with those based on all items in the respective item pools. Furthermore, the relative validity (RV) of CATs was compared with that of the QLQ-C30 scales using known groups validity., Results: For both dimensions, CATs of all lengths resulted in unbiased score estimates. CATs consisting of five or more items had reliability>0.90, correlated ≥ 0.97 with the full scale, and had root mean square error <0.25. The average RVs for these CATs ranged 1.02-1.33, indicating possible savings in sample size requirements of 3-42% using CAT., Conclusion: The CAT versions of PF and FA exhibited high levels of measurement precision and efficiency. The potential savings in sample size requirements using CATs compared with those using the original QLQ-C30 scales were typically 20% or more., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: We investigated whether circulating endothelial cells (CECs) predict clinical outcome of first-line chemotherapy and bevacizumab in metastatic colorectal cancer (mCRC) patients., Patients and Methods: In a substudy of the randomized phase II FNCLCC ACCORD 13/0503 trial, CECs (CD45- CD31+ CD146+ 7-amino-actinomycin- cells) were enumerated in 99 patients by four-color flow cytometry at baseline and after one cycle of treatment. We correlated CEC levels with objective response rate (ORR), 6-month progression-free survival (PFS) rate (primary end point of the trial), PFS, and overall survival (OS). Multivariate analyses of potential prognostic factors, including CEC counts and Köhne score, were carried out., Results: By multivariate analysis, high baseline CEC levels were the only independent prognostic factor for 6-month PFS rate (P < 0.01) and were independently associated with worse PFS (P = 0.02). High CEC levels after one cycle were the only independent prognostic factor for ORR (P = 0.03). High CEC levels at both time points independently predicted worse ORR (P = 0.025), 6-month PFS rate (P = 0.007), and PFS (P = 0.02). Köhne score was the only variable associated with OS., Conclusion: CEC levels at baseline and after one treatment cycle may independently predict ORR and PFS in mCRC patients starting first-line bevacizumab and chemotherapy.

Although the treatment of pancreatic ductal adenocarcinoma (PDAC) remains a huge challenge, it is entering a new era with the development of new strategies and trial designs. Because there is an increasing number of novel therapeutic agents and potential combinations available to test in patients with PDAC, the identification of robust prognostic and predictive markers and of new targets and relevant pathways is a top priority as well as the design of adequate trials incorporating molecular-driven hypothesis. We presently report a consensus strategy for research in pancreatic cancer that was developed by a multidisciplinary panel of experts from different European institutions and collaborative groups involved in pancreatic cancer. The expert panel embraces the concept of exploratory early proof of concept studies, based on the prediction of response to novel agents and combinations, and randomised phase II studies permitting the selection of the best therapeutic approach to go forward into phase III, where the recommended primary end point remains overall survival. Trials should contain as many translational components as possible, relying on standardised tissue and blood processing and robust biobanking, and including dynamic imaging. Attention should not only be paid to the pancreatic cancer cells but also to microenvironmental factors and stem/stellate cells.

The outcome for patients with metastatic pancreatic ductal adenocarcinoma is dismal. In this article, we will review current first-line treatments for metastatic pancreatic adenocarcinoma focusing on phase III randomized studies. Single-agent gemcitabine, the reference treatment since 1995, offers only slight benefit. Numerous trials using gemcitabine in combination with different cytotoxic agents have resulted in no major improvement compared to gemcitabine alone. Only the gemcitabine-erlotinib combination has shown a small, but statistically improvement in survival. In selected patients with good performance status ECOG 0-1, no cardiac ischemia and almost normal bilirubin level, the Folfirinox regimen, when compared to gemcitabine as single agent, was associated with more toxicities, but also with significant increased survival and delay in the degradation of quality of life. So, Folfirinox is a new more toxic and more efficient regimen that may be considered in patients with good performance status.

Introduction: Breast cancer is by far the most common form of cancer diagnosis in women. Cancer treatments are long, complex and often cumbersome with numerous side effects. Fatigue is now considered as the most distressing side effect of treatment. Fifty-eight percent to 94% of breast cancer patients experience fatigue during treatment with adjuvant chemotherapy., Objective: The aim of this study is to identify the determinants of cancer-related fatigue, and the long-term effects of the different adjuvant treatments will be explored., Research Design: A prospective longitudinal study in women diagnosed for the first time with stage I-IIIA breast cancer and who have undergone surgery, has been designed to meet the study aims. Recruitment began in September 2008 and target enrollment completion date is December 2010. (clinicaltrials.gov number, NCT01064427). The MFI-20 (Multidimensional Fatigue Inventory) and the EORTC QLQ-C30 (European Organization for Research and Treatment Quality of Life Questionnaire) will be completed, at several times. The follow-up is planned over a 24-month period. We studied adjuvant chemotherapy regimens with anthracyclines or with anthracycline/taxane combination. The LOR (Life Orientation Test) will be completed only at baseline to estimate the level of optimism of the patient and the STAI (State-Trait Anxiety Questionnaire) will be filled to measure a stable propensity to experience anxiety, and tendencies to perceive stressful situations as threatening., Outcomes: The knowledge of determinants should facilitate screening of fatigue, and its evaluation on consequences on the patients' quality of life would allow physicians better help patients cope with the management of fatigue according to the adjuvant regimen., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: In resectable rectal cancer trials, pathological parameters are early preoperative treatment efficacy measures. Their validation as surrogate end points for long-term clinical outcomes would allow to reduce trial duration. The aim was to evaluate potential surrogates for overall survival (OS) and local control (LC) in preoperative T3/T4 rectal cancer trials. Candidate variables included ypT and ypN stages, T downstaging, tumor regression grade (TRG), and circumferential resection margin (CRM) status., Patients and Methods: In the Fédération Francophone de Cancérologie Digestive (FFCD) 9203 trial, 742 eligible patients were randomly assigned to receive preoperative radiotherapy with or without concurrent chemotherapy. Surrogacy was evaluated using Prentice criteria and the proportion of treatment effect (PTE) explained by each potential surrogate., Results: None of the candidate surrogates fulfilled all Prentice criteria. Data analyses did not provide interpretable PTE measures for OS. Regarding LC, the highest PTE was reached by TRG, which explained 12% of the effect on local recurrence. This proportion may not exceed 41% [95% confidence interval (CI) -1% to 41%]. PTE explained by the CRM status was associated with a wide uncertainty (95% CI -81% to 105%), which does not exclude a potentially high degree of surrogacy., Conclusion: In the FFCD 9203 trial, pathological parameters were not surrogate for OS or LC.

Background: This multicenter adjuvant phase III trial evaluated the addition of irinotecan to LV5FU2 in colon cancer patients at high risk of relapse., Patients and Methods: A total of 400 patients with histologically proven primary colon cancer with postoperative N1 detected by occlusion/perforation or N2 were randomised to: A-LV5FU2 [leucovorin 200 mg/m(2), 2-h infusion, 5-fluorouracil (5-FU) 400 mg/m(2) bolus, 600 mg/m(2) 22-h continuous infusion, days 1 and 2] or B-LV5FU2 + IRI (irinotecan 180 mg/m(2) 90-min infusion day 1 + LV5FU2) fortnightly for 12 cycles. Primary end point was disease-free survival (DFS)., Results: Median follow-up was 63 months. Significantly more T4 tumours and 15 or more positive lymph nodes were observed in arm B. 5-FU relative dose intensity (RDI) was >0.80 for 94% and 77% in arms A and B, respectively (P < 0.001). Irinotecan RDI was >0.80 for 70% patients. There were more grades 3 and 4 neutropenia in arm B (4% versus 28%, P < 0.001). The 3-year DFS was 60% [95% confidence interval (CI) 53% to 66%] and 51% (95% CI 44% to 58) in arms A and B, respectively. No difference was observed [hazard ratio (HR) = 1.12, 95% CI 0.85-1.47, P = 0.42] even when adjusted for prognostic factors (adjusted HR = 0.98, 95% CI 0.74-1.31, P = 0.92). The 5-year overall survival (OS) was 67% (95% CI 59% to 73%) and 61% (95% CI 53% to 67%) in arms A and B, respectively., Conclusion: Adjuvant LV5FU2 + IRI compared with LV5FU2 alone in patients at high risk of relapse showed no improvement in DFS and OS.

Unlabelled: At the request of the National Thesaurus of Gastrointestinal Cancer (TNCD), the SOR program undertaken by the French federation of cancer centers and now led by the French National Cancer Institute, completed a systematic review to evaluate the value of perioperative chemotherapy in the management of resectable rectal adenocarcinoma in collaboration with clinician experts., Methods: Results of a systematic literature search using Medline and Embase (from January 1996 to October 2007) were completed by a survey of Evidence- Based Medicine websites. All phase III randomized trials and systematic reviews comparing surgery (alone or associated with adjuvant therapy) to the same treatment plus chemotherapy, or comparing different perioperative chemotherapy modalities in patients with resectable rectal adenocarcinoma, were included in the study. The quality and clinical relevance of the trials were evaluated using validated checklists, allowing to associate each result with its level of evidence. Data synthesis was performed taking into account both efficacy and toxicity outcomes for each intervention. Finally, research recommendations were formulated., Results: Of 29 studies meeting the selection criteria, 19 were included after critical methodological and clinical appraisal. As compared with preoperative radiotherapy, preoperative chemoradiotherapy with 5-fluorouracil and folinic acid does not improve overall or relapse-free survivals but decreases local recurrence rates. Postoperative chemotherapy with 5-fluorouracil and folinic acid does not improve overall or relapse-free survivals, whether the patients received preoperative radiotherapy or preoperative chemoradiotherapy, whereas it seems to decrease local recurrence rates after preoperative radiotherapy but not after preoperative chemoradiotherapy. As compared with postoperative chemoradiotherapy, preoperative chemoradiotherapy with continuous infusion of 5-fluorouracil does not improve overall or relapse-free survivals, but decreases local recurrence rates as well as acute and long-term toxicities. In the absence of preoperative radiotherapy, fluoropyrimidine-based postoperative chemotherapy improves both overall and relapse-free survivals and decreases local recurrence rates., Conclusions: Preoperative chemoradiotherapy reduces the risk of local recurrence as compared with preoperative radiotherapy or postoperative chemoradiotherapy.

With the recent trend of improved survival, there has been a marked interest in reviewing and refining the contribution of health related quality of life (HRQoL) outcome measures of treatment in advanced colorectal cancer. However, if HRQoL data are going to be of clinical value and help both physicians and patients make decisions there is a need for a consensus on both the design and methods of measurement of HRQoL in clinical trials, and an acknowledgement of the interpretation of the outcomes in clinical practice. Whilst it is encouraging to find that the quality of HRQoL measurement in clinical research has improved significantly over the last fifteen years, with a growing number of trial-based HRQoL studies, there is still the potential to improve the use of HRQoL in clinical decision making in advanced colorectal cancer. There is also the need to further refine measurement of HRQoL to provide useful data specific to these patients. It is anticipated that developments such as the liver metastases module EORTC (QLQ-LMC21) questionnaire will increase the sensitivity to change of the generic cancer measure, the EORTC QLQ-C30 and will provide essential HRQoL information regarding the use of treatments in both the curative and palliative settings. Furthermore, easy to use simple tools such as the "minimum standard checklist for evaluating HRQoL outcomes in cancer clinical trials" might be of help in guiding investigators on the basis of minimum criteria.

Purpose: To analyze the prognostic factors of loco regional control (LRC), specific survival (SS) and sphincter conservation (SC) of patients treated by curative and conservative irradiation for an epidermoid cancer of anal canal in our institution., Patients and Methods: From 1976 to 2005, 286 patients (pts) were treated by exclusive radiotherapy (180 pts) or chemo-radiotherapy (106 pts) followed by a brachytherapy boost (233 pts) or external beam radiotherapy boost (24 pts). Forty-three pts were stage I, 154 stage II, 31 stage IIIA and 53 stage IIIB., Results: The mean follow-up was 65 months (range: 1.3-250 months). The 5-years-overall survival and SS rates were 66.4% and 78.1% respectively. In multivariate analysis, tumor size (>or=40 mm) [RR=2.1], node involvement (RR=2.4), and poor response (<75%) to first course irradiation [RR=1.9], local relapse (RR=4.5) and distant metastases were factors of poor prognosis for SS. Five-years-LRC were 71.5% (88% for stage I, 69% for stage II, 77%, for stage IIIA and 60% for stage IIIB). Prognosis factors of LCR were tumor size (RR=2.5), response to first course of irradiation (RR=2.9). SC was 71% at 5 years. Prognosis factors of SC were tumor size (RR=1.9) and response to first course of irradiation (RR=2.4)., Conclusion: The results of this series are similar to those of the literature. As well as initial tumor extension, response to first course of irradiation was found as prognostic factor on LCR, SS, SC. Our results are similar to other series and brachytherapy seems not to be deleterious. Its impact to local control remains to be evaluated.

Background: The aim of the study was to compare the longitudinal quality of life (QoL) between chemoradiation with or without surgery in patients with locally advanced squamous resectable esophageal cancer included in a randomized multicenter phase III trial (FFCD 9102)., Materials and Methods: All patients with locally advanced resectable (T3-4 N0-1 M0) epidermoid or glandular esophageal cancer (n = 451) received induction chemoradiation. Responders (n = 259) were randomized between surgery (arm A) and continuation of chemoradiation (arm B). The Spitzer QoL Index was scored (0-10) at inclusion and at each follow-up, every 3 months during 2 years. QoL at baseline and longitudinal changes were respectively compared with univariate ANOVA and mixed-model analysis of variance for repeated measurements. The time interval between the follow-up was assessed and the same analyses were performed among survivors with 2 years of follow-up., Results: The squamous histology was predominant in both arms. The mean QoL score decreased between baseline and the first follow-up and between the first and the second follow-ups. QoL scores at the first follow-up were comparatively worse in arm A than in arm B (7.52 versus 8.45, P < 0.01), whereas the longitudinal QoL study showed no difference between treatments (adjusted P = 0.26). Furthermore, the longitudinal QoL was not different (adjusted P = 0.23) among survivors with 2 years of follow-up., Conclusions: Among patients responding to induction chemoradiation, surgery and continuation of chemoradiation had the same impact on QoL in patients with locally advanced, resectable esophageal cancer although a significantly greater decrease in the Spitzer Index was observed in the postoperative period.

Patient satisfaction is now recognised as an important quality of care outcome which is particularly relevant in oncology. Adapted from the EORTC In-Patsat32, the Out-Patsat35 is a 35-item satisfaction with care questionnaire measuring cancer outpatients' perception of hospital doctors and nurses, as well as aspects of care organisation and services. This study assessed the psychometric properties of this scale. Patients undergoing ambulatory chemotherapy (CT) or radiotherapy (RT) in 7 cancer centres in France were invited to complete at home the Out-Patsat35 as well as EORTC QLQ-C30 for psychometric testing. Of 416 eligible patients recruited, 96% returned the questionnaire. Most patients (71% in CT; 69% in RT) completed this scale within 15 minutes and the mean rate of item omission was only 4.4%. Confirmatory analyses revealed good convergent validity and excellent internal consistency, although some subscales within the Out-Patsat35 were relatively highly correlated. Items and subscales of the Out-Patsat35 and of the QLQ-C30 were not significantly correlated, underlying that the two questionnaires are assessing quite distinct concepts. The subscales of the Out-Patsat35 were not related to age, gender and education, suggesting a cultural evolution in French cancer patients towards a greater homogeneity in their opinion toward care. This study supports the acceptability to patients, and the psychometric properties of the EORTC Out-Patsat35 questionnaire.

Purpose: The tumor-activated fluoropyrimidine capecitabine achieves response rates superior to those of bolus 5-fluorouracil/leucovorin (5-FU/LV) as first-line treatment for metastatic colorectal cancer (CRC), with favorable safety and fewer hospitalizations. Capecitabine is also at least as effective as bolus 5-FU/LV in the adjuvant setting, again with a favorable safety profile. Improved outcomes with capecitabine versus bolus 5-FU/LV in the adjuvant setting have been shown in overall trial populations and in patients aged >or= 70 years. Capecitabine/oxaliplatin (XelOx) is a safe and active combination for the first-line treatment of metastatic CRC., Patients and Methods: This post hoc analysis of a large phase II trial compared data from older and younger patients treated with first-line XelOx: oxaliplatin 130 mg/m(2) intravenously on day 1 followed by oral capecitabine 1,000 mg/m(2) twice daily for 14 days every 3 weeks., Results: The median age of the overall population (N = 96) was 64 years (range, 34-79 years), including 52 younger patients (< 65 years of age) and 44 older patients (>or= 65 years of age). Both age groups received a median of 8 cycles (range, 1-26 cycles) of XelOx. The XelOx regimen had similar high activity in both groups, with response rates of 58% (95% CI, 43%-71%) and 52% (95% CI, 37%-68%) in younger and older patients, respectively. In addition, time to disease progression and overall survival were similar in both groups (P > 0.5 for both outcomes). The XelOx regimen also had a favorable safety profile, with no clinically relevant differences between older and younger patients. The overall incidence of adverse events (including grade 3/4), dose reductions, and withdrawals because of adverse events were similar in both groups., Conclusion: In the context of an aging population, XelOx provides a highly effective and tolerable first-line treatment for patients with metastatic CRC.

Context: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French regional cancer centers, and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients., Objectives: To elaborate clinical practice guidelines for patients with stomach adenocarcinoma. These recommendations cover the diagnosis, treatment and follow-up of these tumors., Methods: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. The Standards, Options and Recommendations are thus based on the best available evidence and expert agreement., Results: This guidelines presents the synthesis of the data concerning the evaluation of the therapeutic ones. The main questions concern the type of gastrectomy to realize (Total Gastrectomy or gastrectomy subtotal), the extent of the lymphadenectomy (D2, D3 versus D1, D3, D2 versus D4) and the role of postoperative chemotherapy and adjuvant concomitant chemoradiotherapy.

Context: The "Standards, Options and Recommendations" (SOR) project, which started in 1993, is a collaboration between the Federation of French Cancer Centres (FNCLCC), the 20 French Regional Cancer Centres, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients., Objectives: To update clinical practice guidelines for first line palliative chemotherapy in patients with metastatic colorectal cancer previously validated in 1995, then updated in 1997 and published again in 1998. These recommendations do not cover second line treatment., Methods: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGs according to the definitions of the Standards, Options and Recommendations project. Once the guidelines have been developed, they are reviewed by independent reviewers., Results: This article is a summary version of the updated clinical practice guidelines with algorithms. The main questions addressed by the expert group in this update concerned (1) Which patients should be treated? (2) What is the best treatment duration? (3) Which treatment should be administered? The new data identified concerning which patients to treat and the duration of treatment were consistent with the data presented in the initial report and did not modify the original recommendations from 1997. The new data available represent stronger evidence than those in the original report (Two good-quality meta-analyses published since 1997). A new guideline concerning patients who are 75 years old or more has been added. Concerning, the new evidence identified has modified the guidelines for the therapeutic schema to adopt from 1997. These modifications concern irinotecan, oxaliplatin, oral fluoropyrimidines and methotrexate. Treatment with irinotecan or oxaliplatin associated with continuous 5FU infusion, modulated with folinic acid (LV5FU2-like) has become a standard. The use of oral fluoropyrimidines has become an option for patients who refuse hospitalisation or treatment by infusion. The use of methotrexate combined with 5FU is no longer recommended.

Context: "The Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French regional cancer centers, and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients., Objectives: To elaborate clinical practice guidelines for patients with stomach adenocarcinoma. These recommendations cover the diagnosis, treatment and follow-up of these tumors., Methods: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. The Standards, Options and Recommendations are thus based on the best available evidence and expert agreement., Results: Adjuvant radiation therapy alone is not a standard treatment for patients with stomach adenocarcinoma. Adjuvant concomitant chemoradiotherapy is not a standard treatment for patients with stage II or III stomach adenocarcinoma R0, with Dl or D2 lymphadenectomy who have undergone surgery. Following surgical resection, adjuvant concomitant chemoradiotherapy should be proposed to patients without denutrition with a lymphadenectomy < Dl (fewer than 15 lymph nodes examined) and those with T3 and/or N+ tumours following the protocol used in the MacDonald trials (SWOG-9008) (Level of evidence B1). Adjuvant concomitant chemoradiotherapy can be administered to patients without denutrition with DI or D2 lymphadenectomy and with involvement of regional lymph nodes (N2 or N3).

Doubts are expressed on the validity of patient satisfaction questionnaires. High satisfaction levels are consistently reported. Within the European Organisation for Research and Treatment of Cancer (EORTC) quality of life group, we developed a cancer inpatient satisfaction questionnaire (QLQ-SAT32), adopting several precautions to overcome the ceiling effect commonly reported in satisfaction ratings. Since patients are often more critical when expressing themselves in an interview, in order to study the validity of the QLQ-SAT32, we assessed the agreement between self- and interview-administered QLQ-SAT32 responses. One hundred and twenty three patients were asked to complete the QLQ-SAT32 at home within 2 weeks of hospital discharge and were randomly allocated to participate in a telephone interview-administration of the QLQ-SAT32, either before or after self-completing the QLQ-SAT32. One hundred and four of them completed both modalities of questionnaire administration. Correlation and agreement between self- and interview-administered QLQ-SAT32 ratings were examined, for each subscale and the general satisfaction item of the QLQ-SAT32, using Spearman correlation, intra-class correlation coefficients (ICC) or weighted kappa coefficients. Agreement showed excellent for the doctors' and nurses' subscales and satisfactory for the services' subscale and the general satisfaction single item. The telephone interview-administration modality did not prove an adequate procedure to assess the validity of a patient satisfaction questionnaire.

Bisphosphonates constitute the standard treatment for cancer hypercalcemia and prevention of complications of metastatic bone disease. Various clinical endpoints have been used to evaluate the impact of bisphosphonates on bone metastases. This literature review is focused on the analgesic effect of bisphosphonates and their impact on quality of life (QoL) in patients with bone metastases from breast cancer. Twenty-five randomized trials studying bisphosphonates with pain and/or QoL as primary or secondary endpoints were considered. These studies were analyzed with following criterias : study type, primary cancer, drug scheduling, number of patients included, associated specific treatment, primary and secondary endpoints, pain assessment, and QoL assessment. The results are in favor of an efficacy of bisphosphonates in bone pain, even when not always statistically significant and with an important variability in assessment criterias and tools. QoL assessment with validated, reliable scales (EORTC QLQ-C30, Rotterdam Symptom Checklist...) has been performed in 9 studies. The use of bisphosphonates with systemic and radiation therapy increases QoL or reduces QoL deterioration. Despite some methodological limitations, these studies indicate a beneficial effect on bone pain, and an improvement in the QoL of patients with metastatic bone disease of breast cancer. Because of a lack of systemic data, reliable analysis of the results is difficult. Several questions remain open about which bisphosphonates and route of administration to choose, and the variable effects on different primaries., (Copyright John Libbey Eurotext 2003.)

Background: The aim of this study was to determine the maximum-tolerated dose (MTD) and the recommended dose of irinotecan and oxaliplatin with a fixed 5-fluorouracil (5-FU)/leucovorin (LV) regimen in patients with metastatic solid tumors., Patients and Methods: The trial was designed to evaluate escalating doses of oxaliplatin and irinotecan, starting at 60 mg/m2 and 90 mg/m2, respectively, given at day 1 with the full-dose LV5FU2 regimen, given on days 1 and 2 as follows: folinic acid 200 mg/m2 followed by 5-FU 400 mg/m2 bolus and 600 mg/m2 22 h continuous infusion, every 2 weeks. The second cohort of patients was treated at the recommended dose for oxaliplatin and irinotecan with the simplified LV5FU regimen: on day 1, a 2-h infusion of folinic acid (400 mg/m2), followed by a 10-min intravenous bolus of 5-FU (400 mg/m2), followed by a continuous infusion of 5-FU (2400 mg/m2) over 46 h., Results: Thirty-four patients were treated at the following dose levels (oxaliplatin/irinotecan mg/m2): 60/90, 60/120, 85/120, 85/150, 85/180, 85/200 and 85/220 and seven patients were treated at the recommended dose with the simplified LV5FU scheme. The MTD was reached at dose level 85/220 mg/m2 but the recommended dose chosen for the second step was 85/180 mg/m2 to keep a better compliance with the biweekly schedule. Main grade 3/4 toxicities per patient included the following: neutropenia in 78% (febrile episodes in 12%), diarrhea in 27%, nausea/vomiting in 24% and peripheral neuropathy in 37% (Lévi's scale). Antitumor activity was observed at almost all dose levels. Most objective responses were observed in digestive malignancies, since 10 out of 11 were obtained in five colorectal cancers, two pancreatic cancers, two cholangiocarcinoma and one gastric cancer., Conclusion: The recommended dose for the triple association is 85/180 mg/m2 of oxaliplatin and irinotecan, respectively, with LV5FU2 or simplified LV5FU. The antitumor activity in gastrointestinal malignancies should be evaluated in phase II studies in different tumor types.

Purpose: Until the 1990s, the patient's duration of life was the main measure for determining the value of palliative chemotherapy for colorectal cancer. Quality of life recently appeared as a main end point. The aim of this article is to provide an overview of the instruments used to measure quality of life in patients with metastatic colorectal cancer, to review the published data and to analyse the bias and methodological problems., Current Knowledge and Key Points: QoL is a multidimensional subjective concept, which can be measured using psychometric instruments. Quality of life measurement has a descriptive and prognostic value. Results from quality of life assessment in randomized trials have given useful information and help patients and physicians to choose between treatment options. More than half of the patients with palliative chemotherapy had at least stabilization of quality of life. Response to chemotherapy and side-effects influence quality of life. Quality of life assessment clearly requires methodological improvement. Missing data are a particularly difficult problem, which should be improved by a better organization., Future Prospects and Projects: Psychometric properties of EORTC QLQ-CR38 et FACT-C should be checked in French language. An international consensus on methods of measurement of quality of life in oncology is warranted to enhance compliance, to better interpret quality of life results et to optimize publications of precise quality of life data.

Background: This multicenter, phase II, open-label study evaluated the antitumor efficacy and safety of oxaliplatin and raltitrexed (Tomudex) in non-pretreated advanced colorectal cancer patients., Patients and Methods: Seventy-one patients received oxaliplatin 130 mg/m(2) and raltitrexed 3 mg/m(2) intravenously on an outpatient basis every 3 weeks. All patients had histologically proven metastatic colorectal adenocarcinoma, performance status

Background: Vinorelbine and cisplatin are active against squamous cell oesophageal carcinoma. The purpose of this phase II study was to evaluate the efficacy and safety of vinorelbine plus cisplatin in previously untreated patients with metastatic squamous cell oesophageal carcinoma and to estimate the progression-free survival, overall survival and quality of life (QoL) of the patient population., Patients and Methods: Seventy-one eligible patients were entered into a study of vinorelbine 25 mg/m2 on days 1 and 8 plus cisplatin 80 mg/m2 on day 1, every 3 weeks. Degree of dysphagia relief was monitored and QoL was measured using the EORTC QLQ-C30., Results: All eligible patients were assessed for response and 24 achieved a confirmed partial response (33.8%; 95% confidence interval 23-46); the median duration of response was 6.8 months, progression-free survival was 3.6 months and median survival of the whole group was 6.8 months. Toxicity was mainly related to neutropenia (grade 3/4 in 41% of patients). At cycle 2, 43% of the patients reported at least a moderate improvement in global health status/QoL and 25% experienced a large improvement., Conclusions: Vinorelbine plus cisplatin represents a well-tolerated active palliative regimen for patients with advanced squamous cell carcinoma of the oesophagus. This combination may offer a better therapeutic index than cisplatin-5-fluorouracil.

The quality of life (QOL) of cancer patients can be measured by semi structured interview or by validated QOL instruments. Late effect toxicity scales can be used but do not account for the different domains of QOL measured by the patient. Health related quality of life can be measured by health general questionnaire or by specific cancer questionnaires. These instruments add to a core questionnaire, modules according for the organ or the toxicity of the treatments developed to evaluate cancer treatments. Some questions can be added to evaluate special domain as medical expenses, personal insurance. Some specific questionnaires for long-term survivors are available, which explore patient's satisfaction according to this status for different domains of QOL or quote different aspects in comparison with a normal population and are transformed into an utility index. There is no gold standard to measure long-term survivors' quality of life. The use of proxy is limited by discrepancies observed in the evaluation of pain, psychological symptoms and general quality of life. QOL can be evaluated in a cohort of patients in a longitudinally study or better in a case control study. Examples of QOL evaluation of different cancers sites are given.

Context: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the French National Federation of Comprehensive Cancer Centers (FNCLCC), the 20 French Cancer Centers and specialists from French Public University or General Hospitals, and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome of cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery., Objectives: To define, according to the definitions of the Standards, Options and Recommendations project, the characteristics of the main tumor markers in colorectal cancer and their potential role in the management of patients with this malignancy., Methods: Data were identified by searching Medline and the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 117 independent reviewers, and to the medical committees of the 20 French Cancer Centers., Results: The main recommendations for the tumor markers in colorectal cancer are: 1) The carcinoembryonic antigen (CEA) is the reference serum marker (standard). 2) All the analyses for a given patient must be performed in the same laboratory, using the same technique (standard, expert agreement). 3) CEA or CA 19-9 should not be used for screening or diagnosis (standard, level of evidence B2). 4) High initial serum concentration of CEA is of bad predictive value (standard, level of evidence C). CEA is an independent prognostic factor of survival in colorectal cancers with lymph node metastases (standard, level of evidence B2). 5) CEA is the most sensitive biological parameter for the screening of hepatic metastases (standard, level of evidence B2). 6) CEA serum concentration before palliative chemotherapy is an independent prognostic factor of survival (standard, level of evidence B2). The combination of CEA assay with imagery techniques and clinical examination can help monitor the response to palliative chemotherapy (standard), in particular in non measurable disease (standard, expert agreement). 7) In 65% of the cases, CEA is the first indicator of relapse (standard, level of evidence B2). CEA is the choice marker for monitoring patients with colorectal cancer (standard, level of evidence B2). 8) A sustained biological follow-up including CEA assay can be used to predict the operability of recurring tumors (standard, level of evidence B2). Nevertheless, no survival advantage has been shown (standard).

Purpose: To analyse toxicity and response to a new scheme of neoadjuvant chemotherapy (CT) and concomitant radiochemotherapy (RT-CT) for locally advanced anal canal squamous-cell carcinoma (ACC)., Patients and Methods: Eighty patients with an ACC > 40 mm and/or with lymph node involvement were included (1 T1, 52 T2, 14 T3, 13 T4, 18 N0, 30 N1, 32 N2-N3). Two cycles of 5-fluorouracil (5-FU) and CDDP were delivered as neoadjuvant CT and two during RT-CT. Pelvic (+/- inguinal) RT delivered 45 Gy in 25 fractions of 1.8 Gy. Involved fields were boosted after a one to two month gap (15-20 Gy). The median follow-up was 29 months., Results: One patient died of a pulmonary embolism on day 4. All patients received the entire treatment, with reduced 5-FU doses in 27% of the cases because of acute toxicity. Sixty-four grade 3 and five grade 4 toxicities were observed. No toxic death occurred. Complete response (CR) and partial response (PR) rates were, respectively, 10% and 51% after neoadjuvant CT, 67% and 28% after RT-CT and 93% and 5% after treatment completion (including 4 abdomino-perineal resections). The three-year actuarial overall, tumour-specific, colostomy-free, relapse-free, disease-free and event-free survivals were 86%, 88%, 73%, 70%, 67% and 63%, respectively., Conclusions: Tolerance was good. After neoadjuvant CT, most of the patients were objective responders. After treatment completion, all but five achieved CR. The long-term results confirm the durability of local control and low toxicity on the sphincter. An ongoing phase III intergroup trial analyses the impact of neoadjuvant CT, and the benefit of a high-dose boost irradiation, on local control and colostomy-free survival.

Introduction: Despite improvements in surgical techniques and perioperative mortality, only slight improvements in the 5-year survival of patients with esophageal cancer have been observed in the last 20 years. Many patients with apparently localized cancer will have recurrences or metastatic disease despite surgery with curative resection. Consequently, multimodal therapies, including chemotherapy and radiotherapy, were introduced. This review outlines and critically analyzes current non-surgical treatments, including palliative care., Current Knowledge and Key Points: Esophageal cancers appear to be chemosensitive but the median duration of response is short and toxicity consistent, especially in metastatic disease. Consequently, palliative chemotherapy should be offered preferably within a clinical trial. Chemotherapy as the only adjuvant treatment cannot be recommended outside clinical trials. Radiotherapy alone as a curative treatment has been proven to be inferior to chemoradiotherapy in inoperable tumors. Some data support the use of preoperative chemoradiotherapy, but randomized trials are conflicting. A pathological complete response has been identified as a favorable prognostic factor for survival. Self-expanding esophageal metal stents are a simple and effective palliative treatment of malignant dysphagia and can be considered as the reference treatment in patients with obstruction of the lower esophagus or with fistula., Future Prospects and Projects: Taxanes should be evaluated in randomized studies using chemotherapy or chemo-radiotherapy. Progress in radiotherapy, such as accelerated fractionation, greater radiation dose, and the addition of brachytherapy, will increase locoregional control and probably survival. The role of secondary surgery in patients responding to chemoradiotherapy still needs to be answered.

Background: Chemotherapy (5-fluorouracil-mitomycin C) concomitant with radiotherapy (RT) increases local control and colostomy-free survival in advanced anal canal carcinomas (ACC). The purpose of this prospective trial was to analyse the toxicity of and response to an induction chemotherapy combining 5-fluorouracil (5-FU) and CDDP administered concomitantly with irradiation., Patients and Methods: Thirty patients (24 F/6 M, mean age 60, range 38-74) with an advanced ACC > 40 mm and/or with node involvement were prospectively treated (1 T1, 16 T2, 8 T3, 5 T4, 10 N1, 1 N2, 8 N3) from November 1994 to January 1996. Two induction and two concomitant cycles of 5-FU (800 mg/ m2 D1-4 infusion) and CDDP (80 mg/i.v./m2 at D1) were delivered. RT consisted of 45 Gy (1.8 Gy/fr, 5 fr/w) on pelvis +/- inguinal nodes or 30 Gy (3 Gy/fr, 4 fr/w) by direct perineal field. A boost (15-20 Gy) was delivered six weeks later., Toxicity: one patient died of a pulmonary embolism on D4. The remaining 29 received the entire treatment, with reduced 5-FU doses in 11 patients because of acute toxicity. The RT boost was delayed for one patient (aplasia). In 109 cycles, 3 grade 4 and 17 grade 3 toxicities were observed; there were no toxic deaths. Tumor response: the complete response (CR) and partial response (PR) rates were, respectively, 11% and 61% after induction chemotherapy, 59% and 31% after concomitant radiochemotherapy and 96% and 0% two months after completion of the treatment. No tumor progression was observed., Conclusion: the treatment was well tolerated and there was good compliance. After induction chemotherapy, most of the patients were in PR, with some even in CR. After completion of the treatment all but one were in CR. The tumor response and the long term results of 50 patients will be analysed before initiation of a randomised trial is considered.