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Intrahepatic cholangiocarcinoma (iCCA) is the second most common malignant primary liver cancer. iCCA may develop on an underlying chronic liver disease and its incidence is growing in relation with the epidemics of obesity and metabolic diseases. In contrast, perihilar cholangiocarcinoma (pCCA) may follow a history of chronic inflammatory diseases of the biliary tract. The initial management of CCAs is often complex and requires multidisciplinary expertise. The French Association for the Study of the Liver wished to organize guidelines in order to summarize the best evidence available about several key points in iCCA and pCCA. These guidelines have been elaborated based on the level of evidence available in the literature and each recommendation has been analysed, discussed and voted by the panel of experts. They describe the epidemiology of CCA as well as how patients with iCCA or pCCA should be managed from diagnosis to treatment. The most recent developments of personalized medicine and use of targeted therapies are also highlighted. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most frequent cancer worldwide, accounts for about 10% of the total cancer cases, and ranks as the second cause of death by cancer. CRC is more prevalent in developed countries in close causal relation with occidental diets. Due to anatomy, the diet has a strong impact on CRC. High contents in meat are acknowledged risk factors whereas a diet rich in fruits and vegetables is an established CRC protective factor. Fruits and vegetables contain numerous Bioactive Food Components (BFCs), physiologically active food compounds, beneficial on health. Preventive and therapeutic benefits of BFCs in cancer have increasingly been reported over the past 20 years. BFCs show both chemopreventive and anti-tumor properties in CRC but more interestingly, abundant research describes BFCs as enhancers of conventional cancer treatments. Despite these promising results, their clinical transferability is slowed down by bioavailability interrogations and their poorly understood hormetic effect. In this review, we would like to reposition BFCs as well-fitted for applications in CRC. We provide a synthetic overview of trustworthy BFC applications in CRC, with a special highlight on combinatory approaches and conventional cancer treatment potentiation strategies. [ABSTRACT FROM AUTHOR]

L'actualité en oncologie radiothérapie est marquée par les résultats d'essais stratégiques particulièrement pour les cancers de l'œsophage et du rectum. Pour l'adénocarcinome de l'œsophage, en situation préopératoire, les résultats de l'étude ESOPEC ont montré un bénéfice de survie de la chimiothérapie périopératoire par 5-fluoro-uracile, leucovorine oxaliplatine, taxotère en comparaison à la chimioradiothérapie (irradiation de 41,4 Gy avec une chimiothérapie concomitante par carboplatine/paclitaxel). En situation exclusive, l'étude CONCORDE n'a pas montré de bénéfice de l'escalade de dose et la dose standard reste 50 Gy. Pour le cancer du pancréas opérable, l'étude NRG/RTOG0848 qui comparait la chimiothérapie adjuvante avec ou sans chimioradiothérapie complémentaire a retrouvé une augmentation significative de la probabilité de survie sans maladie à 5 ans dans le sous-groupe de patients sans atteinte ganglionnaire. Pour les cancers du rectum, l'actualisation à 7 ans des résultats de l'étude PRODIGE 23 a confirmé le bénéfice non seulement en termes de survie sans récidive mais également de survie globale d'une chimiothérapie néoadjuvante par 5-fluoro-uracile, acide folinique, irinotécan et oxalipalatine avant la chimioradiothérapie, alors que l'actualisation de l'étude RAPIDO a montré un taux de rechute locale inacceptable dans le bras expérimental. L'actualisation de l'étude OPRA a montré un taux de survie avec conservation d'organe à 5 ans significativement supérieur en faveur du bras chimioradiothérapie suivie de la chimiothérapie en comparaison à la chimiothérapie d'induction première suivie de chimioradiothérapie. Une étude de phase 2 incluant 41 patients atteints d'un cancer du rectum localement avancé avec défaillance du système de réparation de l'ADN, a montré qu'un traitement exclusif par immunothérapie anti-PDL1 (dostarlimab) pendant 6 mois permettait une réponse clinique complète sans recours à un traitement complémentaire (ni radiothérapie, ni chirurgie). Pour le carcinome épidermoïde du canal anal, la survie et les profils de toxicité des patients inclus dans la cohorte anabase traités pour une tumeur de petit stade (T1 ou T2) ont été comparés selon qu'ils aient reçu exclusivement de la radiothérapie ou de la chimioradiothérapie. L'ajout d'une chimiothérapie à la radiothérapie ne montrait pas de bénéfice mais augmentait la toxicité et le risque d'allongement du traitement en raison d'interruption. Current events in radiotherapy oncology are marked by the results of strategic trials, particularly for esophageal and rectal cancers. For resectable esophageal adenocarcinoma, results of the ESOPEC study showed a benefit in overall survival from the perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin and docetaxel compared to chemoradiotherapy (41.4 Gy radiotherapy and carboplatin/paclitaxel chemotherapy). In definitive setting, the CONCORDE study did not show any benefit from dose escalation and the standard dose remains 50 Gy. For resectable pancreatic cancer, the NRG/RTOG0848 study that compared adjuvant chemotherapy with or without chemoradiotherapy found a significant increase of the 5-year disease-free survival rate in the subgroup of node-negative patients. For rectal cancers, the 7-year update of PRODIGE 23 study confirmed the benefit in disease-free- and overall survival of neoadjuvant folinic acid, fluorouracil, irinotecan and oxaliplatin chemotherapy before chemoradiotherapy of T3, T4 or N+ adenocarcinoma, while the update of the RAPIDO study revealed an unacceptable local recurrence rate in the experimental arm. The update of the OPRA study shows a significantly higher 5-year organ preservation rate in favor of the chemoradiotherapy arm followed by consolidation chemotherapy compared to induction chemotherapy followed by CRT. A phase 2 study, including 41 patients with mismatch repair deficient, locally advanced rectal cancer reported that exclusive treatment with anti-PDL1 immunotherapy (dostarlimab) for 6 months resulted in complete clinical response without the need of additional treatment (neither radiotherapy nor surgery). For anal carcinoma, the analysis of survival and toxicity profiles of patients treated for a small stage T1 or T2 tumor were compared depending on whether they received exclusive radiotherapy or chemoradiotherapy. The addition of chemotherapy to radiotherapy did not show any survival benefit but significantly increased toxicity and the risk of radiotherapy disruption. [ABSTRACT FROM AUTHOR]

Current events in radiotherapy oncology are marked by the results of strategic trials, particularly for esophageal and rectal cancers. For resectable esophageal adenocarcinoma, results of the ESOPEC study showed a benefit in overall survival from the perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin and docetaxel compared to chemoradiotherapy (41.4Gy radiotherapy and carboplatin/paclitaxel chemotherapy). In definitive setting, the CONCORDE study did not show any benefit from dose escalation and the standard dose remains 50Gy. For resectable pancreatic cancer, the NRG/RTOG0848 study that compared adjuvant chemotherapy with or without chemoradiotherapy found a significant increase of the 5-year disease-free survival rate in the subgroup of node-negative patients. For rectal cancers, the 7-year update of PRODIGE 23 study confirmed the benefit in disease-free- and overall survival of neoadjuvant folinic acid, fluorouracil, irinotecan and oxaliplatin chemotherapy before chemoradiotherapy of T3, T4 or N+ adenocarcinoma, while the update of the RAPIDO study revealed an unacceptable local recurrence rate in the experimental arm. The update of the OPRA study shows a significantly higher 5-year organ preservation rate in favor of the chemoradiotherapy arm followed by consolidation chemotherapy compared to induction chemotherapy followed by CRT. A phase 2 study, including 41 patients with mismatch repair deficient, locally advanced rectal cancer reported that exclusive treatment with anti-PDL1 immunotherapy (dostarlimab) for 6 months resulted in complete clinical response without the need of additional treatment (neither radiotherapy nor surgery). For anal carcinoma, the analysis of survival and toxicity profiles of patients treated for a small stage T1 or T2 tumor were compared depending on whether they received exclusive radiotherapy or chemoradiotherapy. The addition of chemotherapy to radiotherapy did not show any survival benefit but significantly increased toxicity and the risk of radiotherapy disruption., (Copyright © 2024. Published by Elsevier Masson SAS.)

Purpose: The influence of human immunodeficiency virus (HIV) infection on clinical outcomes in patients receiving (chemo)radiation therapy (RT) for squamous cell carcinoma of the anus (SCCA) is debated. The objective of this study was to compare efficacy and safety according to HIV status in patients with SCCA treated with C/RT., Methods and Materials: Between January 2015 and April 2020, 488 patients with a known HIV status (17.6% HIV+) were treated with radiation therapy for SCCA and included in the FFCD-ANABASE multicentric prospective cohort. Clinical outcomes including overall survival (OS), locoregional recurrence-free survival, colostomy-free survival, response rate at 4 to 6 months, cancer-specific survival, relapse-free survival, and severe acute and late toxicity were compared between HIV+ and HIV- patients., Results: The median follow-up was 35.8 months. HIV+ patients were younger (P < .01) and predominantly male (P < .01). Intensity modulated radiation therapy was performed in 80.7% of patients, and 80.9% received concurrent chemotherapy. A higher proportion of HIV+ patients received induction chemotherapy compared with HIV- patients. No statistically significant difference in overall treatment time or severe acute and late toxicities was found between HIV+ and HIV- patients. In univariate analyses, OS (HR = 2.1 [CI 95% 1.2;3.5], P = .007), locoregional recurrence-free survival (HR = 1.7 [1.1;2.7], P = .02), and colostomy-free survival (HR = 1.7 [1.1;2.6], P = .01) were significantly shorter in HIV+ patients than in HIV- patients. Response rate, cancer-specific survival, and relapse-free survival were not significantly different. The recurrence site was significantly different according to HIV status. In the multivariate analysis, prognostic factors for OS were a World Health Organization performance status of ≥1 for the whole population, as well as HIV+ status for the subgroup of women., Conclusions: HIV+ patients treated with chemo-RT for SCCA have poorer clinical outcomes, especially women. No difference was found in toxicity according to HIV status with intensity modulated radiation therapy technique., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study aimed to evaluate the prognostic value of 18 F-FDG PET/CT qualitative assessment in terms of recurrence-free survival (RFS), colostomy-free survival (CFS), and overall survival (OS) after radiation therapy (RT) of squamous cell carcinoma of the anus (SCCA). Secondary objectives were to evaluate the prognostic value of baseline and posttherapeutic quantitative 18 F-FDG PET/CT parameters in terms of RFS, CFS, and OS. Methods: We included all consecutive patients from the French multicentric cohort FFCD-ANABASE who had undergone 18 F-FDG PET/CT at baseline and 4-6 mo after RT or chemoradiotherapy for a localized SCCA. Qualitative assessments separated patients with complete metabolic response (CMR) and non-CMR. Quantitative parameters were measured on baseline and posttreatment 18 F-FDG PET/CT. RFS, CFS, and OS were analyzed using the Kaplan-Meier method. Associations among qualitative assessments, quantitative parameters, and RFS, CFS, and OS were analyzed using univariate and multivariate Cox regression. Results: Among 1,015 patients treated between January 2015 and April 2020, 388 patients (300 women and 88 men) from 36 centers had undergone 18 F-FDG PET/CT at diagnosis and after treatment. The median age was 65 y (range, 32-90 y); 147 patients (37.9%) had an early-stage tumor and 241 patients (62.1%) had a locally advanced-stage tumor; 59 patients (15.2%) received RT, and 329 (84.8%) received chemoradiotherapy. The median follow-up was 35.5 mo (95% CI, 32.8-36.6 mo). Patients with CMR had better 3-y RFS, CFS, and OS, at 84.2% (95% CI, 77.8%-88.9%), 84.7% (95% CI, 77.2%-89.3%), and 88.6% (95% CI, 82.5%-92.7%), respectively, than did non-CMR patients, at 42.1% (95% CI, 33.4%-50.6%), 47.9% (95% CI, 38.1%-56.8%), and 63.5 (95% CI, 53.2%-72.1%), respectively ( P < 0.0001). Quantitative parameters were available for 154 patients from 3 centers. The following parameters were statistically significantly associated with 3-y RFS: baseline SUV max (primitive tumor [T]) (hazard ratio [HR], 1.05 [95% CI, 1.01-1.1; P = 0.018]), SUV peak (T) (HR, 1.09 [95% CI, 1.02-1.15; P = 0.007]), MTV 41% (T) (HR, 1.02 [95% CI, 1-1.03; P = 0.023]), MTV 41% (lymph node [N]) (HR, 1.06 [95% CI, 1.03-1.1; P < 0.001]), MTV 41% (T + N) (HR, 1.02 [95% CI, 1-1.03; P = 0.005]), and posttreatment SUV max (HR, 1.21 [95% CI, 1.09-1.34; P < 0.001]). Conclusion: Treatment response assessed by 18 F-FDG PET/CT after RT for SCCA has a significant prognostic value. 18 F-FDG PET/CT could be useful for adapting follow-up, especially for patients with locally advanced-stage tumors. Quantitative parameters could permit identification of patients with a worse prognosis but should be evaluated in further trials., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Introduction: Early-stage anal squamous cell carcinomas (ASCC) are usually treated with chemoradiotherapy (CRT), with good outcomes. Radiotherapy (RT) alone might be sufficient while reducing toxicity., Methods: Patients included in the French prospective FFCD-ANABASE and treated for T1-2N0 ASCC between 2015/01 and 2020/04 were divided into CRT and RT groups. Clinical outcomes and toxicity were reported. Propensity score matching was conducted for 105 pairs of patients., Results: 440 patients were analyzed: 261 (59.3 %) in the CRT group and 179 (40.7 %) in the RT group. The median follow-up was 35.7 months. Patients receiving CRT were younger, had better Performance Status (PS) and larger tumors. No statistical difference was observed for 3-year Disease-free survival (85.3 % vs 83 %, p = 0.28), Overall survival (89.6 % vs 94.8 %, p = 0.69) and Colostomy-free survival (84.5 % vs 87.2 %, p = 0.84) between CRT and RT groups, respectively. Propensity score-matched analysis confirmed these findings. Treatment interruptions were significantly more frequent in the CRT group (36.3 % vs 21.9 %, p = 0.0013), resulting in an Overall Treatment Time (OTT) extended by 7 days. Grade 3 CTCAE v4.0 toxicities were more prevalent in the CRT group (46 % vs 19 %, p < 0.001)., Conclusion: Adding chemotherapy to radiotherapy did not significantly improve outcomes for T1-2N0 ASCC in our study, but increased toxicity and OTT., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: A proportion of rectal cancer patients who achieve a clinical complete response may develop local regrowth. Although salvage appears to provide appropriate local control, the risk of distant metastases is less known., Objective: To compare the risk of distant metastases between patients who achieve a clinical complete response (watch-and-wait strategy) and subsequent local regrowth and patients managed by surgery after chemoradiation., Design: Retrospective multicenter cohort study., Settings: This study used data of patients from 3 institutions who were treated between 1993 and 2019., Patients: Patients with initial clinical complete response (after neoadjuvant therapy) followed by local regrowth and patients with near-complete pathological response (≤10%) after straightforward surgery after chemoradiation were included., Main Outcome Measures: Univariate and multivariate analyses were performed to identify risk factors for distant metastases. Kaplan-Meier curves were created (log-rank test) to compare survival outcomes. Analyses were performed using time zero as last day of radiation therapy or as date of salvage resection in the local regrowth group., Results: Twenty-one of 79 patients with local regrowth developed distant metastases, whereas only 10 of 74 after upfront total mesorectal excision following neoadjuvant chemoradiation therapy ( p  = 0.04). Local regrowth and final pathology (ypT3-4) were the only independent risk factors associated with distant metastases. When using date of salvage resection as time zero, distant metastases-free survival rates were significantly inferior for patients with local regrowth (70% vs 86%; p  = 0.01)., Limitations: Small number of patients, many neoadjuvant therapies, and selection bias., Conclusions: Patients undergoing watch-and-wait strategy who develop local regrowth are at higher risk for development of distant metastases compared to patients with near-complete pathological response managed by upfront surgery after chemoradiation. See Video Abstract., Nuevo Crecimiento Local Y El Riesgo De Metstasis a Distancia Entre Pacientes Sometidos a Observacin Y Espera Por Cncer De Recto Cul Es El Mejor Grupo De Control Estudio Retrospectivo Muticntrico: ANTECEDENTES:Una proporción de pacientes que logran una respuesta clínica completa pueden desarrollar un nuevo crecimiento local. Si bien el rescate parece proporcionar un control local apropiado, el riesgo de metástasis a distancia es menos conocido.OBJETIVO:Comparar el riesgo de metástasis a distancia entre los pacientes que logran una respuesta clínica completa (estrategia de observación y espera) y el nuevo crecimiento local posterior con los pacientes tratados con cirugía después de la quimiorradiación.DISEÑO:Estudio de cohorte multicéntrico retrospectivo.CONFIGURACIÓN:Este estudio utilizó datos de pacientes de 3 instituciones que fueron tratados entre 1993 y 2019.PACIENTES:Pacientes con respuesta clínica completa inicial (después de la terapia neoadyuvante) seguida de crecimiento local nuevo y pacientes con respuesta patológica casi completa (≤10 %) después de cirugía directa después de quimiorradiación.PRINCIPALES MEDIDAS DE RESULTADO:Se realizó un análisis univariante/multivariante para identificar los factores de riesgo de metástasis a distancia. Se crearon curvas de Kaplan-Meier (prueba de rango logarítmico) para comparar los resultados de supervivencia. El análisis se realizó utilizando el tiempo cero como último día de radioterapia (1) o como fecha de resección de rescate (2) en el grupo de recrecimiento local.RESULTADOS:Veintiuno de 79 pacientes con recrecimiento local desarrollaron metástasis a distancia, mientras que solo 10 de 74 después de una cirugía sencilla (p = 0,04). El recrecimiento local y la patología final (ypT3-4) fueron los únicos factores de riesgo independientes asociados con las metástasis a distancia. Cuando se utilizó la fecha de la resección de rescate como tiempo cero, las tasas de supervivencia sin metástasis a distancia fueron significativamente inferiores para los pacientes con recrecimiento local (70 frente a 86 %; p = 0,01).LIMITACIONES:Pequeño número de pacientes, muchas terapias neoadyuvantes, sesgo de selección.CONCLUSIONES:Los pacientes sometidos a observación y espera que desarrollan un nuevo crecimiento local tienen un mayor riesgo de desarrollar metástasis a distancia en comparación con los pacientes con una respuesta patológica casi completa manejados con cirugía por adelantado después de la quimiorradiación. (Traducción-Dr. Xavier Delgadillo )., (Copyright © The ASCRS 2023.)

Background: Organ preservation as a successful management for rectal cancer is an evolving field. Refinement of neoadjuvant therapies and extended interval to response assessment has improved tumour downstaging and cCR rates., Methods: This was a narrative review of the current evidence for all aspects of organ preservation in rectal cancer management, together with a review of the future direction of this field., Results: Patients can be selected for organ preservation opportunistically, based on an unexpectedly good tumour response, or selectively, based on baseline tumour characteristics that predict organ preservation as a viable treatment strategy. Escalation in oncological therapy and increasing the time interval from completion of neaodjuvant therapy to tumour assessment may further increase tumour downstaging and complete response rates. The addition of local excision to oncological therapy can further improve organ preservation rates. Cancer outcomes in organ preservation are comparable to those of total mesorectal excision, with low regrowth rates reported in patients who achieve a complete response to neoadjuvant therapy. Successful organ preservation aims to achieve non-inferior oncological outcomes together with improved functionality and survivorship. Future research should establish consensus of follow-up protocols, and define criteria for oncological and functional success to facilitate patient-centred decision-making., Conclusion: Modern neoadjuvant therapy for rectal cancer and increasing the interval to tumour response increases the number of patients who can be managed successfully with organ preservation in rectal cancer, both as an opportunistic event and as a planned treatment strategy., (© The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Standard treatment consisting of chemoradiotherapy followed by radical surgery with total mesorectal excision, results in good oncologic local control but high morbidity and poor functional results. Since chemoradiotherapy results in 15% pathological complete response, even reaching up to 30% in case of association with neoadjuvant chemotherapy, radical surgery has been recently debated for good responders. Therefore, a de-escalation strategy, by omitting radical surgery in good responders, has recently been developed with two different options: a watch and wait strategy, requiring an accurate clinical and radiological definition of complete response and a local excision strategy including patients with sub-complete response. Ongoing trials focus on response optimization by chemotherapy intensification or radiotherapy dose escalation. However, many questions are still to be answered regarding definition of complete response, follow-up strategy, morbidity of salvage surgery in case of recurrence as well as long-term oncological and functionnal results., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)