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Background and Aims Postoperative recurrence is a major concern in Crohn's disease. The Kono-S anastomosis has been described to reduce the rate of recurrence. However, the level of evidence for its effectiveness remains low. The KoCoRICCO study aimed to compare outcomes between Kono-S anastomosis and conventional anastomosis in two nationwide, prospective cohorts. Methods Adult patients with Crohn's disease, who underwent ileocolonic resection with Kono-S anastomosis, were prospectively included in seven referral centres between 2020 and 2022. Patients with conventional side-to-side anastomosis were enrolled from a previously published cohort. A propensity score analysis was performed to compare recurrence at first endoscopy in a matched 1:2 ratio population. Results A total of 433 patients with ileocolonic anastomosis were enrolled, of whom 155 had a Kono-S anastomosis. Before matching, both groups were unbalanced for preoperative, intraoperative, and postoperative characteristics. After matching patients with available endoscopic follow-up, endoscopic recurrence ≥i2 was found in 47.5% of the Kono-S group and 44.3% of the conventional side-to-side group [ p  = 0.6745]. Conclusions The KoCoRICCO study suggests that Kono-S anastomosis does not reduce the risk of endoscopic recurrence in Crohn's disease compared with conventional side-to-side anastomosis. Further research with a longer follow-up is necessary to determine whether there is a potential benefit on surgical recurrence. [ABSTRACT FROM AUTHOR]

Background Small bowel adenocarcinoma is a rare cancer, and the role of adjuvant chemotherapy for localized disease is still debated. Methods This retrospective multicenter study included all consecutive patients who underwent curative surgical resection for localized small bowel adenocarcinoma between 1996 and 2019 from 3 French cohort studies. Prognostic and predictive factors of adjuvant chemotherapy efficacy were analyzed for disease-free survival and overall survival. The inverse probability of treatment weighting method was applied in the Cox regression model using the propensity score derived from multivariable logistic regression. Results A total of 354 patients were included: median age, 63.5 years; duodenum location, 53.5%; and tumor stage I, II, and III in 31 (8.7%), 144 (40.7%), and 179 (50.6%) patients, respectively. The adjuvant chemotherapy was administered in 0 (0%), 66 (48.5%), and 143 (80.3%) patients with stage I, II, and III, respectively (P  < .0001). In the subgroup analysis by inverse probability of treatment weighting method, a statistically significant disease-free survival and overall survival benefit in favor of adjuvant chemotherapy was observed in high-risk stage II (T4 and/or <8 lymph nodes examined) and III (T4 and/or N2) but not for low-risk stage II (T3 and ≥8 lymph nodes examined) and III (T1-3/N1) tumors (P interaction <.05). Furthermore, tumor location in jejunum and ileum was also a statistically significant predictive factor of response to adjuvant chemotherapy in stage II and III tumors (P interaction <.05). Conclusion In localized small bowel adenocarcinoma, adjuvant chemotherapy seems to provide a statistically significant survival benefit for high-risk stage II and III tumors and for jejunum and ileum tumor locations. [ABSTRACT FROM AUTHOR]

Aim: A stoma exposes patients to several complications which could impair their quality of life (QoL). In the last decade, the market for stoma therapy in France has evolved, with a significant increase in the activities of home health providers, meeting a need for patient follow‐up and companionship. International studies have demonstrated the impact of the stoma therapist (ST) follow‐up on the improvement of an ostomy patient's QoL. However, the impact of home stoma nurse management has not been analysed. In this context we would like to assess the added value on health‐related QoL from the enhanced follow‐up of ostomy patients by STs. Methods: This is a randomized, controlled, open, national and multicentre trial (12 centres) which includes patients with an ostomy who benefit from either standard follow‐up or from an enhanced and personalized follow‐up with, in particular, regular consultations with an ST after discharge. The primary end‐point is the 3‐month QoL score obtained from the Stoma‐QoL questionnaire. The secondary end‐points are satisfaction of the care, comparison of QoL scores (Stoma‐QoL and EuroQuol EQ‐5D) and the economic gains by calculating the consumption of resources between the two arms. There will be a modified intention‐to‐treat analysis with 6‐month follow‐up in both study arms. Discussion: The StomaCare trial will be the first randomized controlled study in France to evaluate the impact on QoL of an enhanced follow‐up at home of ostomy patients by an ST. [ABSTRACT FROM AUTHOR]

Background: Chemoradiotherapy alone is the standard treatment for locally advanced squamous cell anal carcinoma (SCAC). However, up to 50% of patients will experience recurrence; thus, there is a need for new treatments to improve outcomes. Modified docetaxel, cisplatin and 5-fluorouracil (mDCF) is a treatment option for first-line metastatic SCAC, having shown efficacy in the Epitopes-HPV01 and -02 trials (NCT01845779 and NCT02402842). mDCF treatment also plays a role in the modulation of anti-tumor immunity, suggesting it may be a good combination partner for immunotherapy in patients with SCAC. Anti-programmed death protein-1 (PD-1) immunotherapy has been shown to be effective in metastatic SCAC. We therefore designed the INTERACT-ION study to assess the combination of mDCF with ezabenlimab (BI 754091), an anti-PD-1 antibody, followed by chemoradiotherapy, in patients with Stage III SCAC. Methods: INTERACT-ION is a pivotal, open-label, single-arm phase II study in patients with treatment-naïve Stage III SCAC. Patients will receive induction treatment with mDCF (docetaxel 40 mg/m2 and cisplatin 40 mg/m2 on Day 1, 5-fluorouracil 1200 mg/m2 /day for 2 days) every 2 weeks for 4 cycles and ezabenlimab (240 mg given intravenously) every 3 weeks for 3 cycles. In the absence of disease progression at 2 months, two additional cycles of mDCF and one additional cycle of ezabenlimab will be administered. Patients with radiological objective response, pathological complete/near-complete response and biological complete response will then receive an involvednode radiotherapy with intensity-modulated radiation therapy and concurrent chemotherapy, followed by ezabenlimab alone for seven cycles. All other patients will receive standard chemoradiotherapy. The primary endpoint is the clinical complete response rate 10 months after the first cycle of mDCF plus ezabenlimab. Major secondary endpoints are major pathological response and biological complete response after induction treatment. An extensive ancillary biomarker study in tumor tissue and peripheral blood will also be conducted. Discussion: The addition of immunotherapy to chemotherapy is an area of active interest in metastatic anal cancer. This pivotal study will evaluate this combination in the locally advanced setting. Ancillary biomarker studies will contribute to the understanding of predictors of response or resistance to treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Almost 20% of patients with a locally advanced oesophageal cancer presented long-term local control after exclusive chemoradiotherapy (CRT) and could potentially avoid surgery and its morbidity and mortality. With the aim of identifying the patients that would present long-term locoregional control, we analysed in this study the potential of some pre-treatment positron-emission tomography-computed tomography (PET-CT)-based features in predicting long-term responses and local control in patients treated with definitive CRT. Our results show that radiomics allows for the identification of patients with long-term locoregional control. If confirmed on larger populations, our results could allow the identification of patients who are good responders to CRT, and who could potentially avoid surgery. Background: We evaluated the value of pre-treatment positron-emission tomography–computed tomography (PET-CT)-based radiomic features in predicting the locoregional progression-free survival (LR-PFS) of patients with inoperable or unresectable oesophageal cancer. Material and Methods: Forty-six patients were included and 230 radiomic parameters were extracted. After a principal component analysis (PCA), we identified the more robust radiomic parameters, and we used them to develop a heatmap. Finally, we correlated these radiomic features with LR-PFS. Results: The median follow-up time was 17 months. The two-year LR-PFS and PFS rates were 35.9% (95% CI: 18.9–53.3) and 21.6% (95%CI: 10.0–36.2), respectively. After the correlation analysis, we identified 55 radiomic parameters that were included in the heatmap. According to the results of the hierarchical clustering, we identified two groups of patients presenting statistically different median LR-PFSs (22.8 months vs. 9.9 months; HR = 2.64; 95% CI 0.97–7.15; p = 0.0573). We also identified two radiomic features ("F_rlm_rl_entr_per" and "F_rlm_2_5D_rl_entr") significantly associated with LR-PFS. Patients expressing a "F_rlm_2_5D_rl_entr" of <3.3 had a better median LR- PFS (29.4 months vs. 8.2 months; p = 0.0343). Patients presenting a "F_rlm_rl_entr_per" of <4.7 had a better median LR-PFS (50.4 months vs. 9.9 months; p = 0.0132). Conclusion: We identified two radiomic signatures associated with a lower risk of locoregional relapse after CRT. [ABSTRACT FROM AUTHOR]

Background: There is a strong rational of using anti-programmed cell death protein-1 and its ligand (anti-PD-1/L1) antibodies in human papillomavirus (HPV)-induced cancers. However, anti-PD-1/L1 as monotherapy induces a limited number of objective responses. The development of novel combinations in order to improve the clinical efficacy of an anti-PD-1/L1 is therefore of interest. Combining anti-PD-1/L1 therapy with an antitumor vaccine seems promising in HPV-positive (+) cancers. UCPVax is a therapeutic cancer vaccine composed of two separate peptides derived from telomerase (hTERT, human telomerase reverse transcriptase). UCPVax is being evaluated in a multicenter phase I/II study in NSCLC (non-small cell lung cancer) and has demonstrated to be safe and immunogenic. The aim of the VolATIL study is to evaluate the combination of atezolizumab (an anti-PD-L1) and UCPVax vaccine in a multicenter phase II study in patients with HPV+ cancers. Methods: Patients with HPV+ cancer (anal canal, head and neck, and cervical or vulvar), at locally advanced or metastatic stage, and refractory to at least one line of systemic chemotherapy are eligible. The primary end point is the objective response rate (ORR) at 4 months. Patients will receive atezolizumab every 3 weeks at a fixed dose of 1,200 mg in combination with the UCPVax vaccine at 1 mg subcutaneously. Discussion: Anti-cancer vaccines can restore cancer-immunity via the expansion and activation of tumor-specific T cells in patients lacking pre-existing anti-tumor responses. Moreover, preclinical data showed that specific TH1 CD4 T cells sustain the quality and homing of an antigen-specific CD8+ T-cell immunity. In previous clinical studies, the induction of anti-hTERT immunity was significantly correlated to survival in patients with advanced squamous anal cell carcinoma. Thus, there is a strong rational to combine an anti-cancer hTERT vaccine and an immune checkpoint inhibitor to activate and promote antitumor T-cell immunity. This pivotal proof of concept study will evaluate the efficacy and safety of the combination of a telomerase-based TH1 inducing vaccine (UCPVax) and an anti-PD-L1 (atezolizumab) immunotherapy in HPV+ cancers, as well as confirming their synergic mechanism, and settling the basis for a new combination for future clinical trials. [ABSTRACT FROM AUTHOR]

In the era of immune checkpoint inhibitors, understanding the metastatic microenvironment of proficient mismatch repair/microsatellite stable (pMMR/MSS) colorectal cancer (CRC) is of paramount importance to both prognostication and the development of more effective novel therapies. In this study, primary and paired metastasis tissue samples were collected from patients with resectable metastatic CRC treated with adjuvant FOLFOX or peri-operative chemotherapy in the MIROX phase III prospective study. In total, 74 cancer tissues were stained for CD3, CD8, Forkhead box protein 3 (FOXP3), programmed cell death protein-1 (PD-1, invasive front, stromal, intra-epithelial compartments), and programmed death-ligand 1 (PD-L1, tumor, immune cells). The immune profiling of primary CRC had a limited value to predict the immune context of paired metastases for all markers but CD3+. The expression of CD8 and PD-L1 was higher in metastases after neoadjuvant FOLFOX. In metastases, both CD3 T cells at the invasive front and PD-L1 expressions on immune cells were predictive of better disease-free survival. These results show that the effect of FOLFOX on modifying the immune microenvironment in resected CRC metastases and measurement of PD-L1 expression and tumorinfiltrating CD8 T cells in pMMR/MSS metastatic tissue samples could improve treatment strategies of metastatic CRC patients. [ABSTRACT FROM AUTHOR]

Background: Red blood cell (RBC) transfusions are frequently required in the early period after kidney transplantation. However, the consequences of RBC transfusions on long-term outcomes are largely unrecognized. Methods: We conducted a nationwide French cohort study involving all 31 French kidney transplant centers. Patients having received a first kidney transplant between January 1, 2002 and December 31, 2008 were identified through the national registry of the French BioMedecine Agency (Agence de BioMédecine). Number and date of RBC transfusions were collected from the national database of the French transfusion public service. The primary endpoint was transplant failure defined as graft loss or death with a functional graft. Results: Among 12,559 patients included during the study period, 3,483 (28%) were transfused during the first 14 days post-transplant. Median follow-up was 7.6 (7.5-7.8) years. Multivariable analysis determined that post-transplant RBC transfusion was associated with an increased risk in transplant failure (HR 1.650, 95%CI [1.538;1.771] p<0.0001). Both sensitivity and propension score analyses confirmed the previous result. Conclusions: Early red blood cell transfusion after kidney transplantation is associated with increased transplant failure. [ABSTRACT FROM AUTHOR]