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A major advance has been made in the management of rectal cancer, with the emergence in 2021 of total neoadjuvant treatment. The main publications from the RAPIDO and PRODIGE-23 trials reported a significant improvement in progression-free survival and the pathological complete response rate. The aim of this review is to synthesize recent data on neoadjuvant treatment of rectal cancer, to explain the long-term results of the RAPIDO and PRODIGE-23 trials, and to put them into perspective, considering current advances in de-escalation strategies. The update of the 5-year survival data from the RAPIDO trial highlights an increased risk of loco-regional relapse, with 11.7% of relapses in the experimental group and 8.1% in the control group, while the update of the PRODIGE-23 trial confirms the benefits of this treatment regimen, with a significant improvement in overall survival. In addition, the results of the OPRA and PROPSPECT trials confirm the benefit of total neoadjuvant treatment with induction chemotherapy, as well as the possibility of surgical de-escalation in the OPRA trial and radiotherapy in the PROSPECT trial. The challenge for the future is to identify patients who require total neoadjuvant treatment with the aim of curative surgery to obtain a cure without local or distant relapse, and those for whom therapeutic de-escalation can be envisaged., (Copyright © 2024 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Gastrointestinal cancers are one of the most frequent cancers and a leading cause of cancer deaths worldwide. We provide an overview of the most important practice-changing trials that were either published or presented at the international scientific meetings in 2021-2023. Highlights included reports on three phase III trials (CONCORDE/PRODIGE 26, ARTDECO, and a study by Xu et al.) that evaluated dose escalation in the definitive setting for locally advanced oesophageal cancers, as well as two phase III trials that evaluated the role of chemotherapy (neo-AEGIS) and targeted therapy (NRG/RTOG 1010) in the neoadjuvant setting for adenocarcinoma oesophageal cancers or gastroesophageal junction cancer. CheckMate 577 evaluated nivolumab in patients who had residual pathological disease after neoadjuvant chemoradiation followed by complete resection. The use of radiation therapy for borderline and locally advanced pancreatic cancer is also discussed (SMART and CONKO-007 trials). Stereotactic body radiation therapy followed by sorafenib was compared to sorafenib alone in patients with hepatocellular carcinoma in the NRG/RTOG 1112 study. New options in the management of rectal cancer are emerging such as total neoadjuvant treatment (PRODIGE 23, RAPIDO, PROSPECT), organ preservation (OPRA, OPERA), and the role of immunotherapy in patients with DNA mismatch-repair deficient/microsatellite instability. Finally, preliminary results of the ACT 4 trial that evaluated de-escalation in anal cancer are presented., (Copyright © 2023 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Gastric cancer is the 6th most common cancer in the world. Gastric adenocarcinomas can be divided into two groups: gastroesophageal junction adenocarcinomas and distal gastric adenocarcinomas, with different risk factors and potentially different therapeutic strategies. Therapeutic strategy for esogastric adenocarcinoma is multimodal. Gastric adenocarcinomas are managed with surgery and peri-operative chemotherapy. Gastroesophageal junction adenocarcinomas can either be treated surgically after neoadjuvant chemoradiotherapy or in the same way than gastric adenocarcinomas. There is currently no evidence of superiority of either treatment strategy. Recently, nivolumab has been validated as an adjuvant therapy for patients with esophageal cancer who received preoperative chemoradiotherapy and had residual tumor on the surgical specimen. In the absence of preoperative treatment, adjuvant chemoradiotherapy or chemotherapy should be discussed on a patient-by-patient basis. Currently, there is not indication for targeted therapies, nor for adapting postoperative treatment according to the response to preoperative treatment. The only validated indication for immunotherapy is as adjuvant treatment of esophageal cancer, but many studies are ongoing and may change practices in the future. The objective of this review is to synthesize the literature concerning the management of localized esogastric adenocarcinoma., (Copyright © 2022 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Despite recent advances, the prognosis of pancreatic adenocarcinomas remains poor, even for patients with resectable tumors. For these latter, new approaches based on neoadjuvant treatment have been developed. Two components are used: chemotherapy and radiation therapy (RT). Indeed, pre-operative RT has many advantages in terms of efficacy and tolerance. It increases notably the chances of subsequent complete tumor resection. Several prospective trials are currently ongoing to clarify its place in the therapeutic arsenal. Another crucial question is to know which is the best RT technique: conventional normofractionated chemoradiotherapy or hypofrationated stereotactic body RT?, (Copyright © 2022 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

We present the updated recommendations of the French society for radiation oncology on radiotherapy of oesophageal cancer. Oesophageal cancer still remains a malignant tumour with a poor prognosis. Surgery remains the standard treatment for localized cancers, regardless of histology. For locally advanced stages, surgery remains a standard for adenocarcinomas after neoadjuvant treatment with chemotherapy or chemoradiotherapy. However, it is a therapeutic option after initial chemoradiotherapy for stage III squamous cell carcinomas, given the increased morbidity and mortality with a multimodal treatment, which results in an equivalent overall survival with or without surgery. Preoperative or exclusive chemoradiotherapy should be delivered according to validated regimens with an effective total dose (50Gy), if surgery is not planned or if the tumour is deemed resectable before chemoradiotherapy. Intensity-modulated radiotherapy significantly reduces irradiation of the lungs and heart and may reduce the morbidity of this treatment, especially in combination with surgery. In case of exclusive chemoradiotherapy, dose escalation beyond 50Gy is not currently recommended. Some technical considerations still remain questionable, such as the place of prophylactic lymph node irradiation, adaptive radiotherapy, evaluation of response during and after chemoradiotherapy and the value of proton therapy., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

For many years, adjuvant chemoradiotherapy remained essential in the therapeutic management of gastric and pancreatic adenocarcinomas. For these tumours, surgical excision, the only hope of offering the patient prolonged survival, is only possible in 20% of cases. The median survival of operated patients is only 12 to 20 months due to the frequency of locoregional and/or metastatic recurrences. For stomach cancers, adjuvant chemoradiotherapy is justified by the results of the phase III trial Intergroup 0116 published by MacDonald et al. The gain in survival was at the cost of significant toxicity. This treatment was supplanted in the early 2000s by perioperative chemotherapy. Currently, neoadjuvant chemoradiotherapy clinical studies are ongoing with the aim of improving treatments observance and tolerance. For pancreatic cancers, the role of adjuvant chemoradiotherapy has long been discussed because of trials with contradictory results. Neoadjuvant radiotherapy has many advantages in terms of efficacy and tolerance. It increases the chances of subsequent complete tumour resection. Several prospective trials are currently ongoing to clarify its place in the therapeutic arsenal., (Copyright © 2020 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Neoadjuvant treatment (NT) for pancreatic head cancer may allow some patients to undergo curative resection, but its impact on postoperative complications remains unclear. A systematic review and meta-analysis were performed to compare overall postoperative morbidity, pancreatic fistula, and mortality between patients who underwent upfront surgery and those who underwent neoadjuvant therapy first. Forty-five studies with 3359 patients were included. No significant differences in morbidity and mortality rates associated with NT for pancreatic head cancer were detected in this study., (© 2020 Wiley Periodicals, Inc.)

Background: Patients with borderline (BR) or locally advanced (LA) pancreatic adenocarcinoma (PAC) are often treated with induction FOLFIRINOX (FLX). However, the role of additional preoperative chemoradiotherapy (CRT) is controversial. The aim of this study is to evaluate its impact in patients who underwent resection after induction FLX., Patients and Methods: Retrospective analysis of prospective consecutive surgical BR or LA PAC patients after induction FLX in 23 French centers between November 2010 and December 2015, treated with or without preoperative additional CRT (FLX vs FLX + CRT groups)., Results: Two hundred three patients were included (106 BR, 97 LA PAC). Median number of FLX cycles was 6 (range 1-30); 50% (n = 102) of patients received additional CRT. Median duration between diagnosis and surgery was 5.4 and 8.7 months (P = 0.001) in the FLX and FLX + CRT group, respectively. The 90-day mortality, major complications, and pancreatic fistula rates were 4.4%, 17.7%, and 5.4%, respectively. After 45.1 months follow-up, overall survival (OS) and disease-free survival were 45.4 months and 16.2 months, respectively. Patients with additional CRT had higher R0 resection rate (89.2% vs 76.3%; P = 0.017), ypN0 rate (76.2% vs 48.5%; P < 0.001), and higher rate of pathologic major response (33.3% vs 12.9%; P = 0.001). In the FLX + CRT group, patients had lower rate of locoregional relapse (28.3% vs 50.7%; P = 0.004). Patients with additional CRT had longer OS than those receiving FLX alone (57.8 vs 35.5 months; P = 0.007)., Conclusions: Pathological results and survival data argue for interest in additional CRT. Prospective studies on an intention-to-treat basis are needed to confirm these results.

Background: To assess local control, survival and conversion to resectability among locally advanced pancreatic cancer (LAPC) patients treated with induction chemotherapy (ICT) followed by chemoradiotherapy treatment using intensity-modulated radiation therapy (IMRT)., Material and Methods: Between 2007 and 2012, 134 LAPC patients were treated with ICT followed by IMRT. After chemoradiotherapy, 40 patients received maintenance chemotherapy., Results: With a median follow-up of 20 months, median overall survival (OS) was 23 months. One- and two-year OS was 85% and 47%, respectively. On multivariate analysis, progression of disease after IMRT was associated with worse OS. Cumulative incidence of local failure was 10% at one year and 36% at two years. Twenty-six patients (19%) underwent resection after chemoradiotherapy including 22 patients (85%) with negative margins. On multivariate analysis, response to IMRT was associated with surgery (p = .01). Acute grade 3-4 hematologic and non-hematologic toxicity rates were 26% and 4.5%, respectively., Conclusion: IMRT is safe in patients with LAPC. Patients with non-progressive LAPC after ICT and who received IMRT had high rates of local control and prolonged survival.

Localized oesophageal and gastric cancers have a poor prognosis. In oesophageal cancer, external radiotherapy combined with concomitant chemotherapy is accepted as part of the therapeutic armamentarium in a curative intent in the preoperative setting for resectable tumours; or without surgery in inoperable patients or non-resectable tumours due to wide local and/or regional extension. Data from the literature show conflicting results with no clinical evidence in favour of either a unique dose protocol or consensual target volume definition in the setting of exclusive chemoradiation. In the preoperative setting, chemoradiotherapy has become the standard in oesophageal cancer, even though there is no evidence that surgery may be beneficial in locally advanced tumours that respond to radiotherapy and chemotherapy. The main cause of failure after exclusive chemoradiotherapy in oesophageal cancer is locoregional relapse suggesting that doses and volumes usually considered may be inadequate. In gastric cancer, radiotherapy may be indicated postoperatively in patients with resected tumours that include less than D2 lymph node dissection or in the absence of perioperative chemotherapy. Preoperative chemoradiotherapy in gastric cancers is still under investigation. The evolving techniques of external radiotherapy, such as image-guided radiotherapy (IMRT) and volumetric modulated arctherapy (VMAT) have reduced the volume of lung and heart exposed to radiation, which seems to have diminished radiotherapy-related morbi-mortality rates. Given this, quality assurance for radiotherapy and protocols for radiotherapy delivery must be better standardized. This article on the indications for radiotherapy and the techniques used in oesophageal and gastric cancers is included in a special issue dedicated to national recommendations from the French society of radiation oncology (SFRO) on radiotherapy indications, planning, dose prescription, and techniques of radiotherapy delivery., (Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Background: Radiation therapy (RT) is an integral component of the management of gastroesophageal junction (GEJ) tumors. We evaluated the use of implanted radiopaque fiducials as tumor surrogates to allow for more focal delivery of RT to these mobile tumors when using respiratory gating (RG) to reduce motion., Material and Methods: We analyzed four-dimensional computed tomography scans of 20 GEJ patients treated with RG and assessed correlation between tumor and implanted fiducial motion over the whole respiratory cycle and within a clinically realistic gate around end-exhalation. We evaluated fiducial motion concordance in 11 patients with multiple fiducials., Results: Gating reduced anterior-posterior (AP) and superior-inferior (SI) mean tumor and fiducial motions by over 50%. Fiducials and primary tumor motions were moderately correlated: R(2) for AP and SI linear fits to the entire group were 0.54 and 0.68, respectively, but the correlation had strong inter-patient variation. For all patients with multiple fiducials, relative in-gate displacements were below 3 mm; results were similar for eight of 11 patients over the whole cycle., Conclusion: Implanted fiducial and gross tumor volume (GTV) motions correlate well but the correlation is patient-specific and may be dependent on the location of the fiducials with respect to the GTV., Competing Interests: statement The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Background: Pancreatic adenocarcinoma is characterized by a high frequency of KRAS mutations and frequent deregulation of the epidermal growth factor receptor (EGFR) and other EGFR family members such as HER2/ErbB2. The EGFR inhibitor erlotinib is approved for treatment of pancreatic cancer, but has shown modest activity in most patients., Objective: Here we investigated the activity of afatinib, a second-generation irreversible pan-EGFR family kinase inhibitor, alone or in combination with ionizing radiation, toward pancreatic cancer cells., Methods: The influence of afatinib on cell proliferation, cell cycle distribution, clonogenic survival, nuclear fragmentation, ploidy, and centrosome amplification following irradiation was determined. Expression and phosphorylation of HER receptors, Akt, DNA-PKcs, and ERK1/2 was characterized by Western blot analysis., Results: Afatinib was growth-inhibitory for all three cell lines but cytotoxic only toward BxPC3 (KRAS (wt)) and Capan-2 (KRAS (mut)) cells, both of which express high levels of EGFR, HER2, and HER3 receptors. Afatinib increased the radiosensitivity of BxPC3 and Capan-2 cells, prevented the radio-induced phosphorylation of Akt, and induced mitotic catastrophe following irradiation. In comparison, Panc-1 cells (KRAS (mut)) expressing low levels of EGFR family receptors were resistant to afatinib-induced radiosensitization., Limitations: These results must be confirmed in vivo., Conclusions: Afatinib showed cytotoxic and radiosensitizing effects toward a subset of pancreatic cancer cells which was closely correlated with expression of EGFR, HER2, and HER3 receptors, but not with KRAS status.

Pancreatic adenocarcinoma remains a devastating disease with a 5-year survival rate not exceeding 6%. Treatment of this disease remains a major challenge. This article reviews the state-of-the-art in the management of this disease and the new innovative approaches that may help to accelerate progress in treating its victims. After careful pre-therapeutic evaluation, only 15-20% of patients diagnosed with a pancreatic cancer (PC) are eligible for upfront radical surgery. After R0 or R1 resection in such patients, evidence suggests a significantly positive impact on survival of adjuvant chemotherapy comprising 6 months of gemcitabine or fluorouracil/folinic acid. Delayed adjuvant chemoradiation is considered as an option in cases of positive margins. Borderline resectable pancreatic cancer (BRPC) is defined as a tumour involving the mesenteric vasculature to a limited extend. Resection of these tumours is technically feasible, yet runs the high risk of a R1 resection. Neoadjuvant treatment probably offers the best chance of achieving successful R0 resection and long-term survival, but the best treatment options should be determined in prospective randomised studies. Gemcitabine has for 15 years been the only validated therapy for advanced PC. Following decades of negative phase III studies, increasing evidence now suggests that further significant improvements to overall survival can be achieved via either Folfirinox or gemcitabine + nab-paclitaxel regimens. Progress in systemic therapy may improve the chances of resection in borderline resectable pancreatic cancer (BRPC) or locally advanced PC. This requires first enhancing knowledge of the genetic events driving carcinogenesis, which may then be translated into clinical studies., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Pancreatic carcinoma is one of the leading causes of cancer-related mortality. At the time of diagnosis, 30% of patients present with a locally advanced pancreatic carcinoma (LAPC). As circulating tumor cells (CTCs) count may be a surrogate of the cancer metastatic abilities, CTC detection rates and prognostic value were studied in a prospective cohort of LAPC patients., Patients and Methods: An LAP07 international multicenter randomized study assesses in patients whose LAPC is controlled after 4 months of chemotherapy whether chemoradiotherapy could increase survival versus continuation of chemotherapy. A subgroup of patients included in the LAP07 trial was screened for CTCs (CellSearch®) before the start of the chemotherapy and after 2 months of treatment. Patient characteristics and survival were obtained prospectively and were correlated with CTC detection., Results: Seventy-nine patients were included. One or more CTCs/7.5 ml were detected in 5% of patients before treatment and in 9% of patients after 2 months of treatment (overall detection rate: 11% of patients). CTC positivity was associated with poor tumor differentiation (P = 0.04), and with shorter overall survival (OS) in multivariable analysis (RR = 2.5, P = 0.01), together with anemia., Conclusions: The evaluation of micrometastatic disease using CTC detection appears as a promising prognostic tool in LAPC patients.

Background: Neoadjuvant chemoradiation therapy for locally unresectable and borderline resectable pancreatic cancer may allow some patients to a undergo a resection, but whether or not this increases post-operative morbidity remains unclear., Methods: The post-operative morbidity of 29 patients with initially locally unresectable/borderline pancreatic cancer who underwent a resection were compared with 29 patients with initially resectable tumours matched for age, gender, the presence of comorbidities (yes/no), American Society of Anesthesiology (ASA) score, tumour location (head/body-tail), procedure (pancreaticoduodenectomy/distal pancreatectomy) and vascular resection (yes /no). Wilcoxon's signed ranks test was used for continuous variables and McNemar's chi-square test for categorical variables., Results: Compared with patients with initially resectable tumours, patients who underwent a resection after pre-operative chemoradiation therapy had similar rates of overall post-operative complications (55% versus 41%, P = 0.42), major complications (21% versus 21%, P = 1), pancreatic leaks and fistulae (7% versus 10%, P = 1) and mortality (0% versus 1.7%, P = 1)., Conclusion: Although some previous studies have suggested differences in post-operative morbidity after chemoradiation, our case-matched analysis did not find statistical differences in surgical morbidity and mortality associated with pre-operative chemoradiation therapy., (© 2013 International Hepato-Pancreato-Biliary Association.)

About 7200 new cases of pancreatic adenocarcinomas are diagnosed each year in France. At the time of diagnosis, an efficient carcinologic surgery will not be possible for nearly 80% of patients, in relation to loco-regional extension or metastatic dissemination. After surgical resection, the median survival of resected patients ranges from 12 to 20 months, with a high rate of relapses. Currently, the use of radiotherapy for patients with pancreatic cancer is controversial. In adjuvant setting, the standard treatment is six months of chemotherapy with FUFOL or gemcitabine. Chemoradiation (CRT) may improve the survival of patients with incompletely resected tumors (R1). This must be validated in a prospective trial. Neoadjuvant CRT is a promising treatment but always under evaluation. For the treatment of patients with locally advanced tumors, there is not a standart treatment. A strategy of initial chemotherapy followed by CRT for non progressive patients is under evaluation. Whereas in the first trials of CRT large fields were used, the current trend is to reduce the treated volumes to improve tolerance. The delineation of target volumes has been improved by the use of simulation CT. The aims of this work are to precise the radio-anatomical particularities, the pattern of spread of pancreatic cancer and the principles of 3D conformal radiotherapy illustrated with a clinical case., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Introduction: At the request of the National Thesaurus of Gastrointestinal Cancer (TNCD), the SOR program undertaken by the French Federation of Cancer Centers (FNCLCC) and now led by the French National Cancer Institute (INCa), completed a systematic review to evaluate the value of chemoradiotherapy (CRT) in the management of locally advanced pancreatic adenocarcinoma in collaboration with clinician experts., Methods: Results of a systematic literature search using Medline (from 1980 to 2008) were completed by a consult of evidence-based medicine websites. All phase III randomized trials and systematic reviews concerning non resectable locally advanced pancreatic adenocarcinoma and non metastatic (stage III) were included in the study. Some phase II trials were also included if no phase III trials were retrieved. The following interventions were compared: CRT versus best supportive care (BSC), CRT versus radiotherapy, and CRT versus chemotherapy. The modalities of CRT regimens and the sequences of chemotherapy-CRT versus CRT were also studied. The quality and clinical relevance of the trials were evaluated using validated checklists, allowing associating each result with a level of evidence. Data synthesis was performed considering both efficacy and toxicity outcomes for each intervention., Results: Nineteen references were included in this systematic review: 2 meta-analyses, 11 randomized trials, 5 non-randomized trials and 1 randomized trial only published in abstract form. After a clinical and methodological critical appraisal, compared to the alternative BSC, concomitant CRT increases overall survival (C). Concomitant CRT compared to the radiotherapy alone increases the overall survival (B1) but is more toxic (B1). Concomitant CRT compared to chemotherapy alone is not superior in terms of survival (B1) and increases toxicity (A). Concerning administration modalities of radiotherapy, recent data are in favour to a limited irradiation to the tumoral volume (C) and to a total dose of 50-60 Gy in association with 5-FU. The study of radiotherapy associated drugs shows that 5-FU is the reference (B1) and the value of gemcitabine must be proved in randomized trials. Finally, the study of sequences chemotherapy-CRT has recently showed that induction chemotherapy before CRT improves survival (C). Validation of this strategy in a randomized trial is warranted., Conclusion: The use of CRT for locally advanced pancreatic adenocarcinoma is based on a few randomized trials even if this treatment appears superior in terms of survival compared to BSC and radiotherapy alone. This review shows the need to conduct other specific randomized trials in order to validate the value of CRT, especially compared to chemotherapy alone.

Background: According to previously reported Groupe Coordinateur Multidisciplinaire en Oncologie (GERCOR) studies in locally advanced pancreatic cancer (LAPC), concomitant chemoradiotherapy (CCRT) may be recommended for patients who do not experience disease progression after systemic induction chemotherapy (CT). To further improve patient outcome with classical fluorouracil (FU)-based CCRT, this study was designed to prospectively investigate a CCRT with FU infusion and weekly oxaliplatin after 2 months of gemcitabine and oxaliplatin (GEMOX) induction chemotherapy., Patients and Methods: Nonpretreated patients with LAPC having WHO performance status (PS) of 0 to 2 received four induction cycles of GEMOX (gemcitabine 1 g/m(2) on day 1 and oxaliplatin 100 mg/m(2) on day 2; day 1 of a 15-day cycle). One month after cycle 4, patients who did not experience disease progression with PS 0 to 2 received 45 Gy over 5 weeks + 10 Gy (as a concomitant boost during the last 2 weeks) of radiotherapy (RT), with daily 250 mg/m(2) FU as a continuous infusion and 60 mg/m(2)of oxaliplatin weekly., Results: Of 59 patients, 50 patients (84.7%) received CCRT, whereas nine patients did not because of disease progression (seven patients), CT toxicity (one patient), or personal decision (one patient). Forty-four patients (74.5%) completed the fully planned CCRT. Median progression-free survival and overall survival durations were 7.6 and 12.2 months, respectively, for the whole population and 9.4 and 12.6 months, respectively, for patients who completed CCRT. CCRT grade 3 to 4 toxicities (National Cancer Institute Common Toxicity Criteria) were neutropenia (10.4%), thrombocytopenia (8.4%), nausea and vomiting (16.7%), and diarrhea (12.5%)., Conclusion: Concomitant administration of weekly oxaliplatin, continuous-infusion FU, and RT in patients with LAPC is feasible, with an acceptable acute and late safety profile. The encouraging results observed despite a nonoptimal patient selection (owing to the short induction time) indicates that further randomized evaluation to better define the specific role of oxaliplatin in CCRT is deserved.

Purpose: The management of locally advanced (LA) pancreatic cancer patients remains controversial. To select patients who could benefit from chemoradiotherapy (CRT), the therapeutic strategy used by the Groupe Coopérateur Multidisciplinaire en Oncologie (GERCOR) consisted of initial chemotherapy (CT) for at least 3 months. The decision to administer CRT or continue CT in nonprogressive patients was the investigator's choice., Patients and Methods: Retrospective analysis of outcome in 181 patients with LA pancreatic cancer (76 women and 105 men; mean age, 61 years; range, 37 to 85 years) enrolled onto prospective phase II and III GERCOR studies was performed to compare the survival of patients who received CRT with that of patients who continued CT alone., Results: Median progression-free survival (PFS) and overall survival (OS) times for the 181 patients were 6.3 and 11.4 months, respectively. Fifty-three patients (29.3%) had metastatic disease after 3 months of CT and were not eligible for CRT. Among the 128 remaining patients (70.3%) who had no disease progression and who were, therefore, eligible for CRT, 72 (56%) received CRT (group A), whereas 56 (44%) continued with CT (group B). The two groups were balanced for initial characteristics (performance status, sex, age, and type of CT), as well as for induction CT results. In groups A and B, the median PFS times were 10.8 and 7.4 months, respectively (P = .005), and the median OS times were 15.0 and 11.7 months, respectively (P = .0009)., Conclusion: These results suggest that, after control of disease by initial CT, CRT could significantly improve survival in patients with LA pancreatic cancer compared with CT alone. A prospective phase III study is ongoing to evaluate this strategy.

About 5,300 new cases of pancreatic adenocarcinomas are diagnosed each year in France. At the time of diagnosis, an efficient carcinologic surgery will not be possible for nearly 80% of patients, in relation to locoregional extension or metastatic dissemination. After surgical resection, the median survival of resected patients ranges from 12 to 20 months, with a high rate of loco-regional or metastatic relapses. Numerous therapeutic trials, adjuvant or neo-adjuvant, have been conducted in aim of which to improve locoregioanl control and survival rates. Chemotherapy and chemoradiotherapy represent adjuvant treatments. In one trial, a chemotherapy regimen with 5-fluorouracil and folinic acid (FUFOL) has proven its efficience for survival improvement by comparison to chemoradiotherapy and is at this time the reference treatment in Europe. In another trial, using adjuvant gemcitabine results in an improvement in disease-free survival. Some phase III trials are in progress to evaluate new therapeutic strategies. The aim of neoadjuvant strategy using chemoradiotherapy is to enhance the rate of complete resections and by the way local control. This is under evaluation. This paper presents a summary of adjuvant and neoadjuvant trials for patients with potentially resectable pancreatic adenocarcinoma.

Longtemps, la chimioradiothérapie adjuvante est restée incontournable dans la prise en charge thérapeutique des adénocarcinomes gastriques et pancréatiques. Pour ces tumeurs, l'exérèse chirurgicale, seul espoir d'offrir au patient une survie prolongée, n'est possible que dans 20 % des cas. La survie médiane des patients opérés n'est que de 12 à 20 mois en raison de la fréquence des récidives locorégionales et/ou métastatiques. Pour les cancers de l'estomac, la chimioradiothérapie adjuvante est justifiée par les résultats de l'essai de phase III de l'Intergroup 0116, publiés par MacDonald et al. Le gain de survie l'était au prix d'une toxicité non négligeable. Ce traitement a été supplanté au début des années 2000 par la chimiothérapie périopératoire. Actuellement, des essais de chimioradiothérapie néoadjuvante sont en cours dans le but d'améliorer l'observance et la tolérance des traitements. Pour les cancers du pancréas, le rôle de la chimioradiothérapie adjuvante est discuté depuis longtemps en raison d'essais aux résultats contradictoires. La radiothérapie néoadjuvante présente de nombreux avantages en termes d'efficacité et de tolérance. Elle augmente les chances de pouvoir réséquer ensuite la tumeur de manière complète. Plusieurs essais prospectifs sont en cours pour préciser sa place dans l'arsenal thérapeutique. For many years, adjuvant chemoradiotherapy remained essential in the therapeutic management of gastric and pancreatic adenocarcinomas. For these tumours, surgical excision, the only hope of offering the patient prolonged survival, is only possible in 20% of cases. The median survival of operated patients is only 12 to 20 months due to the frequency of locoregional and/or metastatic recurrences. For stomach cancers, adjuvant chemoradiotherapy is justified by the results of the phase III trial Intergroup 0116 published by MacDonald et al. The gain in survival was at the cost of significant toxicity. This treatment was supplanted in the early 2000s by perioperative chemotherapy. Currently, neoadjuvant chemoradiotherapy clinical studies are ongoing with the aim of improving treatments observance and tolerance. For pancreatic cancers, the role of adjuvant chemoradiotherapy has long been discussed because of trials with contradictory results. Neoadjuvant radiotherapy has many advantages in terms of efficacy and tolerance. It increases the chances of subsequent complete tumour resection. Several prospective trials are currently ongoing to clarify its place in the therapeutic arsenal. [ABSTRACT FROM AUTHOR]

At the time of diagnosis, around 20% of patients with pancreatic cancer present at a resectable stage, 50% have metastatic disease and 30% have locally advanced tumour, non-metastatic but unresectable because of superior mesenteric artery or coeliac encasement. Despite advances in chemoradiotherapy and improved systemic chemotherapeutic agents, patients with locally advanced pancreatic cancer suffer from high rates of distant metastatic failure and from local progression, with a median survival time ranging from 5 to 11 months. In the past 30 years, modest improvements in median survival have been attained for these patients treated by chemoradiotherapy or chemotherapy protocols. The optimal therapy for patients with locally advanced pancreatic carcinoma remains controversial. This review aims to evaluate the role of radiotherapy for these patients. [ABSTRACT FROM AUTHOR]

Abstract: Pancreatic carcinoma is the fifth leading cause of cancer-related mortality. The 5-year overall survival is less than 5 %. This very poor prognosis can be explained both by late diagnosis and by treatment resistance, including resistance to radiation therapy. A better understanding of the pancreatic tumorigenesis and knowledge of the most frequent mutations in pancreatic adenocarcinoma (KRAS, p16, TP53, Smad4) open new perspectives for the development of more effective treatments. This review presents the major genetic and molecular alterations in pancreatic cancer that could be targeted to improve radiosensitization. [Copyright &y& Elsevier]

out 7200 pancreatic adenocarcinomas are diagnosed every year in France. In 80% of cases, a complete surgical resection of the tumor, which is the only treatment to provide a long-term survival to the patients, is not feasible due to locoregional or metastatic spread of the disease. After a surgical resection with a curative intent, the median overall survival does not exceed 12 to 20 months due to the tumor relapse. Hence, therapeutic trials have been developed using chemotherapy or chemo/radiotherapy as adjuvant/neoadjuvant treatments combined with surgery in order to achieve better long-term survival. It is now admitted that adjuvant chemotherapy may delay tumor relapse and even increase survival in a subset of patients (10%). This has yet not been demonstrated using chemoradiotherapy. Neoadjuvant treatment with chemo/radiotherapy, especially in patients with bordeline tumour, could increase the rate of resectability in a small number of patients, margin-free surgical resections, and local control of the tumor. These approaches need to be validated prospectively. Finally, in a small number of patients with locally advanced tumors being in good condition, the treatment with chemo/radiotherapy may allow to propose a secondary resection. [ABSTRACT FROM AUTHOR]