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.
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.
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 andP = 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.
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.
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.
Aim
There are few data evaluating the long‐term outcomes of intersphincteric resection (ISR), especially the impact of inclusion of more juxtapositioned and intra‐anal tumours on oncological and ...functional outcomes. We compared the oncological and functional results of patients treated by total mesorectal excision and ISR for low rectal cancer over a 25‐year period.
Method
This is a retrospective study from a single institution evaluating results of ISR over three periods: 1990–1998, 1999–2006 and 2007–2014. Patients treated by partial or total ISR, with or without neoadjuvant chemoradiotherapy, for low rectal cancer (≤ 6 cm from the anal verge) were included. We compared postoperative morbidity, quality of surgery and oncological and functional outcomes in the time periods studied.
Results
Of 813 patients operated on for low rectal cancer, 303 had ISR. Tumour stage did not differ; however, the distance of the tumour from the anorectal junction decreased from 1 to 0 cm (P < 0.001) and the distal resection margin shortened from 25 to 10 mm (P < 0.001) from 1990 to 2014. The postoperative morbidity and quality of surgery did not change significantly over time. The 5‐year local recurrence (4.3% vs 5.9% vs 3.5%; P = 0.741) and disease‐free survival (72% vs 71% vs 75%; P = 0.918) did not differ between the three time periods. Functional results improved during the last period; however, overall 42% of patients experienced major bowel dysfunction.
Conclusion
Pushing the envelope of sphincter‐saving resection in ultra‐low rectal cancer reaching or invading the anal sphincter did not compromise oncological and functional outcomes. The main limitation of the ISR procedure appears to be functional rather than oncological, suggesting that bowel rehabilitation programmes should be developed.
Oncosexuality has recently become a new supportive care mission. Sexual morbidity is, routinely, underestimated and must be questioned. We report here the most frequent disorders for men and for ...women, how to prevent them and how to treat them.
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.
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.
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.
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.
•With standard-of-care trimodality therapy for LARC, the 5-year metastasis rate is 25%-35%.•PRODIGE 23 investigated mFOLFIRINOX induction chemotherapy before standard of care, versus standard of care for LARC.•With 7 years of follow-up, induction chemotherapy significantly improved MFS.•DFS and OS were also significantly improved using mFOLFIRINOX induction chemotherapy.
From surviving fraction to tumour curability, definitions of tumour radioresistance may vary depending on the view angle. Yet, mechanisms of radioresistance have been identified and involve ...tumour-specific oncogenic signalling pathways, tumour metabolism and proliferation, tumour microenvironment/hypoxia, genomics. Correlations between tumour biology (histology) and imaging allow theragnostic approaches that use non-invasive biological imaging using tracer functionalization of tumour pathway biomarkers, imaging of hypoxia, etc. Modelling dose prescription function based on their tumour radio-resistant factor enhancement ratio, related to metabolism, proliferation, hypoxia is an area of investigation. Yet, the delivery of dose painting by numbers/voxel-based radiotherapy with low lineal energy transfer particles may be limited by the degree of modulation complexity needed to achieve the doses needed to counteract radioresistance. Higher lineal energy transfer particles or combinations of different particles, or combinations with drugs and devices such as done with radioenhancing nanoparticles may be promising.
Si les définitions de la radiorésistance des tumeurs peuvent varier selon l’angle de vue, radiobiologique ou clinique, les mécanismes de la radiorésistance sont partiellement identifiés. Ils impliquent des voies de signalisation oncogènes spécifiques aux tumeurs, le métabolisme et la prolifération des tumeurs, le microenvironnement tumoral/hypoxie, et peuvent reposer sur une génomique somatique spécifique. Les corrélations entre la biologie des tumeurs (histologie) et l’imagerie permettent des approches théragnostiques qui utilisent une imagerie biologique non invasive (fonctionnalisation de traceurs des biomarqueurs des voies tumorales, imagerie de l’hypoxie, etc). La modélisation de la fonction de prescription des doses en fonction de leur rapport d’amélioration d’un facteur de radiorésistance des tumeurs, lié au métabolisme, à la prolifération, à l’hypoxie est un domaine en cours d’investigations. Pourtant, la délivrance d’une irradiation très modulée, voxel par voxel, avec des particules à faible transfert d’énergie linéal, peut être limitée par le degré de complexité de la modulation nécessaire pour obtenir les doses requises pour contrer la radiorésistance tumorale. Des particules à transfert d’énergie linéal plus élevé ou des combinaisons de différentes particules, ou des combinaisons avec des médicaments et dispositifs comme celles réalisées avec des nanoparticules améliorant la radioprotection peuvent être envisagées.
Aim
Restorative total mesorectal excision (TME) for rectal cancer after high‐dose pelvic radiotherapy for prostate cancer has been reported to provide an unacceptable rate of pelvic sepsis. In a ...previous publication we proposed that delayed coloanal anastomosis (DCAA) should be performed in this situation. The present study aimed to assess the feasibility and outcomes of this strategy.
Method
Between 2000 and 2018, 1094 men were operated on for rectal cancer in our institution. All men with T2/T3 mid and low rectal cancer with preoperative radiotherapy and restorative TME were considered for this study (n = 416). Patients with external‐beam high‐dose radiotherapy (EBHRT) for prostate cancer (70–78 Gy) were identified and compared with patients with conventional long‐course chemoradiotherapy (CRT) followed by TME. We compared our already published historical cohort (2000–2012), including arm A (CRT + TME; n = 236) and arm B (EBHRT + TME; n = 12), with our early cohort (2013–2018), including arm C (CRT + TME; n = 158) and arm D (EBHRT + TME‐DCAA; n = 10). The end‐points were morbidity, pelvic sepsis, reoperation rate and quality of the specimen.
Results
Overall morbidity was not significantly different between groups. Pelvic sepsis decreased from 50% (arm B) to 10% (arm D) with the use of DCAA (P = 0.074), and was similar between arms A, C and D. Quality of the specimen was not significantly different between the four groups.
Conclusion
Our results suggest that TME with DCAA in patients with previous EBHRT is feasible, with the same postoperative pelvic sepsis rate as conventional CRT.
Radiation therapy of pancreatic cancers Huguet, F.; Rivin del Campo, E.; Orthuon, A. ...
Cancer radiothérapie,
February-April 2022, 2022 Feb-Apr, 2022-02-00, 20220201, Volume:
26, Issue:
1-2
Journal Article
Peer reviewed
We present the update of the recommendations of the French society of oncological radiotherapy on radiotherapy of pancreatic tumors. Currently, the use of radiation therapy for patients with ...pancreatic cancer is subject to discussion. In the adjuvant setting, the standard treatment is six months of chemotherapy with 5-fluorouracile, irinotecan and oxaliplatin. Chemoradiation may improve the survival of patients with incompletely resected tumours (R1). This remains to be confirmed by a prospective trial. Neoadjuvant chemoradiation is a promising treatment especially for patients with borderline resectable tumours. For patients with locally advanced tumours, there is no standard. An induction chemotherapy followed by chemoradiation for non progressive patients reduces the rate of local relapse. Whereas in the first trials of chemoradiation large fields were used, the treated volumes have been reduced to improve tolerance. Tumour movements induced by breathing should be taken in account. Intensity modulated radiation therapy allows a reduction of doses to the organs at risk. Whereas widely used, this technique has poor evidence-based recommendation. Stereotactic body radiation therapy is also being studied, as a neoadjuvant or exclusive treatment.
Nous présentons la mise à jour des recommandations de la Société française de radiothérapie oncologique sur la radiothérapie du cancer du pancréas. La place de la radiothérapie chez les patients atteints d’un cancer du pancréas opérable ou localement évolué est toujours controversée. En situation postopératoire, le traitement standard est une chimiothérapie adjuvante par 5-fluoro-uracile, irinotécan et oxaliplatine pendant six mois. En association avec une chimiothérapie concomitante, la radiothérapie postopératoire permettrait d’améliorer la probabilité de survie des patients en situation de résection tumorale incomplète (R1). Cela reste à démontrer dans un essai prospectif. La chimioradiothérapie néoadjuvante est une approche prometteuse de plus en plus utilisée pour les tumeurs à la limite de la résécabilité (borderline). Pour les tumeurs localement évoluées, il n’existe pas de standard thérapeutique. Une chimiothérapie première suivie chez les patients en situation de non-progression par une chimioradiothérapie permet de diminuer le taux de rechute locale. Alors que dans les premiers essais de radiothérapie pancréatique de grands faisceaux d’irradiation étaient utilisés, les volumes traités ont été réduits afin d’améliorer la tolérance. Les mouvements de la tumeur liés à la respiration doivent être pris en compte. La radiothérapie conformationnelle avec modulation d’intensité permet de diminuer les doses reçues par les organes à risque. Bien que de plus en plus utilisée, elle ne fait pas l’objet d’une validation de la Haute autorité de santé pour cette indication. La radiothérapie stéréotaxique est également à l’étude pour les cancers du pancréas, comme traitement néoadjuvant ou exclusif.
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