Management of non-metastatic anal cancer in the elderly: ancillary study of the French multicenter prospective cohort FFCD-ANABASE.

BACKGROUND: Standard care for non-metastatic squamous cell carcinoma of the anus (SCCA) is chemoradiotherapy, data about elderly patients are scarce. METHODS: All consecutive patients treated for non-metastatic SCCA from the French multicenter FFCD-ANABASE cohort were included. Two groups were defined according to age: elderly (≥75 years) and non-elderly (<75). RESULTS: Of 1015 patients, 202 (19.9%) were included in the elderly group; median follow-up was 35.5 months. Among the elderly, there were more women (p = 0.015); frailer patients (p < 0.001), fewer smokers (p < 0.001) and fewer HIV-infected (p < 0.001) than in the non-elderly group. Concomitant chemotherapy and inguinal irradiation were less frequent (p < 0.001 and p = 0.04). In the elderly group; 3-year overall survival (OS), recurrence-free survival (RFS) and colostomy-free survival (CFS) were 82.9%, 72.4% and 78.0%, respectively; complete response rate at 4-6 months was 70.3%. There were no differences between groups for all outcomes and toxicity. In multivariate analyses for the elderly, PS ≥ 2 and locally-advanced tumors were significantly associated with poor OS (HR = 3.4 and HR = 2.80), RFS (HR = 2.4 and HR = 3.1) and CFS (HR = 3.8 and HR = 3.0); and treatment interruption with poor RFS (HR = 1.9). CONCLUSION: In the FFCD-ANABASE cohort, age did not influence tumor and tolerance outcomes of non-metastatic SCCA. Optimal curative treatment should be offered to elderly patients.

Extranodal nasal-type NK/T lymphoma treated with chemotherapy and radiotherapy: case series from a European tertiary referral center and review of the literature.

PURPOSE: Extranodal nasal-type NK/T-cell lymphoma (ENKTL) is very rare in western countries and few data are available regarding the prognosis and the outcome of patients treated for this disease. We aimed to evaluate the prognosis, the pattern and risk factors of disease failure after combined therapy and also performed a review of the literature. PATIENTS AND METHODS: We retrospectively analyzed 20 patients with (ENKTL) who underwent L­Asparaginase based chemotherapy followed by (chemo-) radiotherapy between 2010 and 2020 in our center. Data on clinical characteristics and irradiation were collected. Failure patterns were recorded as local (tumor site), regional (regional lymph nodes) or distant failure (metastasis and/or nonregional lymph nodes). RESULTS: During a median follow-up period of 46 months, disease failure was observed in 8 patients (40%). The 3­year progression-free survival (PFS) and overall survival (OS) rates were 62.5 and 83.0%, respectively. The failure patterns were local (n = 6, 30%), regional (n = 3, 15%) and distant (n = 4, 20%). Among patients with local failure, all failures occurred within the radiation fields (100%). Univariate analysis showed that bilateral regional lymph node involvement (p = 0.0002), initial circulating EBV viral load ≥ 3.5 log (p = 0.03) and no negativation of EBV PCR after induction CT (p = 0.0497) were independent predictors of PFS. CONCLUSION: Patients with bilateral lymph node involvement and/or high EBV viral load have a significant recurrence rate despite multimodal therapy. These results need to be confirmed by larger studies. Given the high rate of local recurrence within radiotherapy fields, the value of dose escalation should be considered. Patients at risk of relapse should be included in dedicated trials.

Association of Radiochemotherapy to Immunotherapy in unresectable locally advanced Oesophageal carciNoma-randomized phase 2 trial ARION UCGI 33/PRODIGE 67: the study protocol.

BACKGROUND: In case of locally advanced and/or non-metastatic unresectable esophageal cancer, definitive chemoradiotherapy (CRT) delivering 50 Gy in 25 daily fractions in combination with platinum-based regimen remains the standard of care resulting in a 2-year disease-free survival of 25% which deserves to be associated with new systemic strategies. In recent years, several immune checkpoint inhibitors (anti-PD1/anti-PD-L1, anti-Program-Death 1/anti-Program-Death ligand 1) have been approved for the treatment of various solid malignancies including metastatic esophageal cancer. As such, we hypothesized that the addition of an anti-PD-L1 to CRT would provide clinical benefit for patients with locally advanced oesophageal cancer. To assess the efficacy of the anti-PD-L1 durvalumab in combination with CRT and then as maintenance therapy we designed the randomized phase II ARION (Association of Radiochemotherapy with Immunotherapy in unresectable Oesophageal carciNoma- UCGI 33/PRODIGE 67). METHODS: ARION is a multicenter, open-label, randomized, comparative phase II trial. Patients are randomly assigned in a 1:1 ratio in each arm with a stratification according to tumor stage, histology and centre. Experimental arm relies on CRT with 50 Gy in 25 daily fractions in combination with FOLFOX regimen administrated during and after radiotherapy every two weeks for a total of 6 cycles and durvalumab starting with CRT for a total of 12 infusions. Standard arm is CRT alone. Use of Intensity Modulated radiotherapy is mandatory. The primary endpoint is to increase progression-free survival at 12 months from 50 to 68% (HR = 0.55) (power 90%; one-sided alpha-risk, 10%). Progression will be defined with central external review of imaging. ANCILLARY STUDIES ARE PLANNED: PD-L1 Combined Positivity Score on carcinoma cells and stromal immune cells of diagnostic biopsy specimen will be correlated to disease free survival. The study of gut microbiota will aim to determine if baseline intestinal bacteria correlates with tumor response. Proteomic analysis on blood samples will compare long-term responder after CRT with durvalumab to non-responder to identify biomarkers. CONCLUSION: Results of the present study will be of great importance to evaluate the impact of immunotherapy in combination with CRT and decipher immune response in this unmet need clinical situation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT: 03777813.Trial registration date: 5th December 2018.

Clinical outcomes of adapted hypofractionated radiotherapy for bladder cancer in elderly patients.

OBJECTIVE: To investigate the feasibility, efficacy, and safety of trimodal therapy (TMT) using a bifractionated split-course hypofractionated radiotherapy (RT) for non-metastatic muscle-invasive bladder cancer (MIBC) in elderly patients. PATIENTS AND METHODS: We retrospectively reviewed the characteristics and outcomes of patients aged >75 years with non-metastatic MIBC suitable or not for radical cystectomy (RC) and treated with transurethral resection of bladder tumour followed by concomitant radio-chemotherapy (platinum salt and 5-fluorouracil) at two institutions (Saint Louis Hospital, Paris, France and European Georges Pompidou Hospital, Paris, France) between 1990 and 2021. RT consisted of an adapted bifractionated split-course hypofractionated RT. Acute toxicities were reported according to Common Terminology Criteria for Adverse Events version 5.0 and late toxicities were reported according to the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer late radiation morbidity scoring schema. The primary end-point was overall survival (OS). Secondary end-points included other survivals outcomes and safety. RESULTS: A total of 122 patients were identified, with a median (range) follow-up of 51.1 (0.5-210.8) months. In all, 83.5% of patients completed radio-chemotherapy. The OS rate was 61.7% at 3 years and 51.2% at 5 years. In multivariate analysis, the completion of RT and concomitant chemotherapy were significantly associated with better OS and cancer-specific survival. For patients fit for RC, a complete histological response was achieved for 77 patients (91.7%) with radio-chemotherapy and the bladder conservation rate was 90.5%. Acute and late Grade ≥3 toxicities were <5%. CONCLUSION: Bifractionated split-course hypofractionated RT with concomitant chemotherapy regimen appears to be well-tolerated and effective. Trimodal treatment seems to be a curative option for elderly patients unfit for radical surgery compared with palliative care and may contribute to improved survival in these patients.

ELANE neutropenia and solid tumors: Four cases from the French severe chronic neutropenia registry.

Neutropenia related to ELANE gene mutations predisposes patients to infection and leukemia/myelodysplasia, but little is known about the predisposition to cancer. Among a cohort of 147 patients, we identified four with malignant solid tumors (papillary thyroid cancer, anal squamous cell cancer, papillary renal cell carcinoma, and adrenocortical carcinoma), all aged 25-50 years. Three occurred with cyclic neutropenia, and one occurred with severe chronic neutropenia. Previous radiotherapy was identified as a risk factor in one patient. No genetic predisposition was identified in the three other patients.

Analyses of patterns-of-failure and prognostic factors according to radiation fields in early-stage Hodgkin lymphoma.

PURPOSE: Doses and volumes of radiation therapy (RT) for early stages of Hodgkin lymphoma (HL) have been reduced over the last 30 years. Combined modality therapy (CMT) is currently the standard treatment for most patients with early-stage HL. The aim of this study was to analyze the site of relapse after RT according to the extent of radiation fields. PATIENTS AND METHODS: Between 1987 and 2011, 427 patients were treated at our institution with RT ± chemotherapy for stage-I/II HL. Among these, 65 patients who experienced a relapse were retrospectively analyzed. Most patients had nodular sclerosis histology (86 %) and stage-II disease (75.9 %). Bulky disease was present in 21 % and 56 % of patients belonged to the unfavorable risk group according to European Organization for Research and Treatment of Cancer (EORTC)/The Lymphoma Study Association (LYSA) definitions. CMT was delivered to 91 % of patients. All patients received RT with doses ranging from 20 to 45 Gy (mean = 34 ± 5.3 Gy). The involved-field RT technique was used in 59 % of patients. RESULTS: The mean time between diagnosis and relapse was 4.2 years (range 0.3-24.5). Out-of-field relapses were suffered by 53 % of patients. Relapses occurred more frequently at out-of-field sites in patients with a favorable disease status, whereas in-field relapses were associated with bulky mediastinal disease. Relapses occurred later for favorable compared with the unfavorable risk group (3.5 vs. 2.9 years, p = 0.5). From multivariate analyses, neither RT dose nor RT field size were predictive for an in-field relapse (p = 0.25 and p = 0.8, respectively), only bulky disease was predictive (p = 0.018). CONCLUSION: In patients with bulky disease, RT dose and RT field size were not predictive for an in-field relapse. In this subgroup of patients, chemotherapy should be intensified. We confirmed the bad prognosis of early relapses.

Esophageal reconstruction by colon interposition after esophagectomy for cancer analysis of current indications, operative outcomes, and long-term survival.

INTRODUCTION: Colon interposition is an alternative solution for esophageal reconstruction if the stomach cannot be used. The study reviews current indications and results of coloplasty for cancer. METHODS: Patients who underwent colon interposition for gastro-esophageal malignancy were included. Primary coloplasty was defined as upfront colon interposition. Salvage coloplasty was defined as colon interposition after primary reconstruction failure. Mortality, morbidity, function, and survival were evaluated. RESULTS: We included 28 patients (24 men, median age 61 years). Ten (36%) patients underwent primary coloplasty due to previous gastrectomy (n = 5), conduit gastric cancer (n = 2), extensive gastroesophageal involvement (n = 2), and gastric cancer recurrence (n = 1). Salvage coloplasty was performed in 18 (64%) patients for postoperative graft necrosis (n = 5) and intractable strictures (n = 3). Operative mortality, morbidity, and graft necrosis rates were 14% (4/28), 86% (24/28), and 14% (4/28), respectively; there were no significant differences between primary and salvage coloplasty. Survival rates at 1-, 3-, and 5 years were 81%, 51%, and 38%, respectively. Survival was decreased after primary coloplasty when compared to salvage coloplasty (P = 0.03). Nine patients experienced tumor recurrence (primary: n = 6, salvage: n = 3) after coloplasty and eight of them died. CONCLUSION: Colon interposition after esophagectomy is a useful but morbid endeavor. Colon interposition as salvage therapy is associated with improved survival compared to its use as primary esophageal replacement, and colon interposition in the latter cohort should be used with caution due to poor cancer-specific survival in this patient population.

Monocentric Retrospective Study: Efficacy, Feasibility, and Prognostic Factors of Single-Insertion High-Dose-Rate Brachytherapy With 4 Sessions for Locally Advanced Cervical Cancer.

Purpose: This study aims to assess the feasibility and efficacy of high-dose rate (HDR) brachytherapy (BT) administered in a single insertion with 4 treatment sessions for locally advanced cervical cancer and to identify the prognostic factors influencing outcomes. Methods and Materials: We retrospectively analyzed the clinical data of patients with cervical cancer with locally advanced disease (International Federation of Gynecology and Obstetrics 2018 IB-IVB) treated at our institution from January 2014 through December 2021. Each patient received definitive radiation therapy with an external irradiation dosage between 45 and 50.4 Gy along with concurrent chemotherapy. HDR-BT (24 Gy) was prescribed to a high-risk clinical target volume. Results: One hundred thirty-nine patients were included and the HDR-BT program could be fully performed in 136 patients (98%). Over a median follow-up duration of 40.5 months, the 2-year local control (LC), overall survival (OS), and disease-free survival rates stood at 79.4%, 77.7%, and 61.7%, respectively, with 5-year rates at 78.2%, 61.6%, and 55.7%. Multivariate analysis revealed the primary determinant of LC as the tumor's response to external beam radiation therapy as determined via magnetic resonance imaging before BT. Parametrial involvement demonstrated a significant multivariate association with disease-free survival (P = .04). Regarding OS, parametrial invasion (P = .01) and the tumor's response postchemoradiotherapy (P = .02) emerged as significant factors. Regarding chronic toxicities, 18% (25 patients) experienced grade 3 complications. An optimal D2 cc (bowel) threshold of 70 Gy (P = .001) was identified to limit chronic digestive complications of grade 3 or higher. Conclusions: The implementation of single-insertion, 4-session HDR-BT could be performed in 98% of the patients. It yields favorable LC and OS rates, coupled with tolerable toxicity in patients with locally advanced cervical cancer. Response to initial chemoradiotherapy evaluated on pre-BT magnetic resonance imaging is an important prognostic factor and could help to individualize therapeutic strategies.

Chemoradiotherapy versus radiotherapy alone in the management of early-stage anal squamous cell carcinoma: A comparative analysis of the French cohort FFCD-ANABASE.

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.

Efficacy and Toxicity of (Chemo)Radiation Therapy in HIV+ Patients with Squamous Cell Anal Cancer, a Subgroup Analysis of the National Multicenter Cohort FFCD-ANABASE.

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.

Evaluation of early response to concomitant chemoradiotherapy by interim 18F-FDG PET/CT imaging in patients with locally advanced oesophageal carcinomas.

PURPOSE: The best way to assess the response to chemoradiotherapy of locally advanced oesophageal carcinomas is not known. We used (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT to evaluate the metabolic response during chemoradiotherapy and tried to correlate this response to survival. METHODS: Patients with biopsy-proven oesophageal carcinoma underwent FDG PET/CT with evaluation of the standardized uptake value (SUV) before any treatment (SUV1) and during chemoradiotherapy after two cycles of 5-fluorouracil (FU)/cisplatin and 20 Gy (SUV2). Metabolic response was defined as 1-(SUV2/SUV1). Surgery was discussed after 40 Gy and three cycles of chemotherapy. Results of interim PET were not considered for the therapeutic decision. RESULTS: Among 72 patients who underwent a first FDG PET/CT before any treatment, 59 (82 %) could receive the second FDG PET/CT examination. Median survival was 22.2 months with 1-year and 2-year survivals of 70 and 46 %, respectively. Nineteen patients (32 %) underwent surgery. Mean SUV1 and SUV2 were 12.3 ± 6.2 and 6 ± 4.1, respectively (p < 0.001). Using a cut-off for metabolic response of 50 %, sensitivity and specificity for survival were 0.7 and 0.58. The 2-year overall survival of good responders was 62 % as compared to 27 % for poor metabolic responders. A multivariate analysis was performed, including T and N stages, surgery, histology and metabolic response: only metabolic response was significantly (p = 0.009) associated with 2-year survival. CONCLUSION: Early evaluation of metabolic response had a great prognostic value and could help identify good responders to chemoradiotherapy.

The 10-month mortality rate among older patients treated for digestive system cancer during the first wave of the COVID-19 pandemic: The CADIGCOVAGE multicentre cohort study.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has had a dramatic impact on cancer diagnosis and care pathways. Here, we assessed the mid-term impact of the COVID-19 pandemic on older adults with cancer before, during and after the lockdown period in 2020. MATERIALS AND METHODS: We performed a retrospective, observational, multicentre cohort study of prospectively collected electronic health records. All adults aged 65 or over and having been newly treated for a digestive system cancer in our institution between January 2018 until August 2020 were enrolled. RESULTS: Data on 7,881 patients were analyzed. Although the overall 10-month mortality rate was similar in 2020 vs. 2018-2019, the mortality rate among for patients newly treated in the 2020 post-lockdown period was (after four months of follow-up) significantly higher. A subgroup analysis revealed higher mortality rates for (i) patients diagnosed in the emergency department during the pre-lockdown period, (ii) patients with small intestine cancer newly treated during the post-lockdown period, and (iii) patients having undergone surgery with curative intent during the post-lockdown period. However, when considering individuals newly treated during the lockdown period, we observed lower mortality rates for (i) patients aged 80 and over, (ii) patients with a biliary or pancreatic cancer, and (iii) patients diagnosed in the emergency department. DISCUSSION: There was no overall increase in mortality among patients newly treated in 2020 vs. 2018-2019. Longer follow-up is needed to assess the consequences of the pandemic. A subgroup analysis revealed significant intergroup differences in mortality.

Treatment, outcome, and prognostic factors in non-metastatic anal cancer: The French nationwide cohort study FFCD-ANABASE.

INTRODUCTION: International guidelines regarding the treatment of squamous cell carcinoma of the anus (SCCA) recommend intensity-modulated radiotherapy (IMRT) combined with mitomycin-based chemotherapy (CT). The French FFCD-ANABASE cohort aimed at evaluating clinical practices, treatment, and outcomes of SCCA patients. METHODS: This prospective multicentric observational cohort included all non-metastatic SCCA patients treated in 60 French centers from January 2015 to April 2020. Patients and treatment characteristics, colostomy-free survival (CFS), disease-free survival (DFS), overall survival (OS), and prognostic factors were analyzed. RESULTS: Among 1015 patients (male: 24.4 %; female: 75.6 %; median age: 65 years), 43.3 %presented with early-stage(T1-2, N0) and 56.7 % with locally advanced stage (T3-4 or N + ) tumors. IMRT was used for 815 patients (80.3 %) and a concurrent CT was administered in 781 patients, consisting of mitomycin-based CT for 80 %. The median follow-up was 35.5 months. DFS, CFS, and OS at 3 years were 84.3 %, 85.6 %, and 91.7 % respectively in the early-stage group compared to 64.4 %, 66.9 %, and 78.2 % in the locally-advanced group (p < 0.001). In multivariate analyses, male gender, locally-advanced stage, and ECOG PS ≥ 1 were associated with poorer DFS, CFS, and OS. IMRT was significantly associated with a better CFS in the whole cohort and almost reached significance in the locally-advanced group. CONCLUSION: Treatment of SCCA patients showed good respect for current guidelines. Significant differences in outcomes advocate for personalized strategies by either de-escalation for early-stage tumors or treatment intensification for locally-advanced tumors.

Prognostic significance of anti-p53 and anti-KRas circulating antibodies in esophageal cancer patients treated with chemoradiotherapy.

BACKGROUND: P53 mutations are an adverse prognostic factor in esophageal cancer. P53 and KRas mutations are involved in chemo-radioresistance. Circulating anti-p53 or anti-KRas antibodies are associated with gene mutations. We studied whether anti-p53 or anti-KRas auto-antibodies were prognostic factors for response to chemoradiotherapy (CRT) or survival in esophageal carcinoma. METHODS: Serum p53 and KRas antibodies (abs) were measured using an ELISA method in 97 consecutive patients treated at Saint Louis University Hospital between 1999 and 2002 with CRT for esophageal carcinoma (squamous cell carcinoma (SCCE) 57 patients, adenocarcinoma (ACE) 27 patients). Patient and tumor characteristics, response to treatment and the follow-up status of 84 patients were retrospectively collected. The association between antibodies and patient characteristics was studied. Univariate and multivariate survival analyses were conducted. RESULTS: Twenty-four patients (28%) had anti-p53 abs. Abs were found predominantly in SCCE (p = 0.003). Anti-p53 abs were associated with a shorter overall survival in the univariate analysis (HR 1.8 [1.03-2.9], p = 0.04). In the multivariate analysis, independent prognostic factors for overall and progression-free survival were an objective response to CRT, the CRT strategy (alone or combined with surgery [preoperative]) and anti-p53 abs. None of the long-term survivors had p53 abs. KRas abs were found in 19 patients (23%, no difference according to the histological type). There was no significant association between anti-KRas abs and survival neither in the univariate nor in the multivariate analysis. Neither anti-p53 nor anti-KRas abs were associated with response to CRT. CONCLUSIONS: Anti-p53 abs are an independent prognostic factor for esophageal cancer patients treated with CRT. Individualized therapeutic approaches should be evaluated in this population.

The Role of Radiotherapy in Treating Kaposi's Sarcoma in HIV Infected Patients.

Kaposi's sarcoma (KS) is a radiosensitive cancer regardless of its form (classical, endemic, AIDS-related, and immunosuppressant therapy-related). Radiotherapy (RT) is an integral part of the therapeutic management of KS. RT may be used as the main treatment, in the case of solitary lesions, or as palliative therapy in the disseminated forms. The dose of RT to be delivered is 20-30 Gy by low-energy photons or by electrons. The complete response rate after RT is high, around 80-90%. This treatment is well tolerated. However, patients should be informed of the possible risk of the development of late skin sequelae and the possibility of recurrence. With the advent of highly active antiretroviral therapy (HAART), the indications for RT treatment in HIV-positive patients have decreased.

Ten-Year Outcomes of Hypofractionated Postmastectomy Radiation Therapy of 26 Gy in 6 Fractions.

PURPOSE: To investigate the efficacy and long-term side effects of hypofractionated postmastectomy radiation therapy (HFRT-PM) of 26 Gy in 6 fractions over 5 weeks. METHODS AND MATERIALS: We retrospectively reviewed characteristics and outcomes of patients with stage I to III breast cancer treated with HFRT-PM between 2000 and 2009. Treatment provided 4 fractions of 4 Gy (days 1, 3, 15, 17) and then 2 fractions of 5 Gy (days 29 and 31) over 5 weeks. The treatment techniques were applied by using 3-dimensional conformal radiation therapy of the chest wall with regional nodal volume if required. RESULTS: We identified 454 patients with a median follow-up of 10.6 years (range, 0.5-22.9). Regional nodal irradiation was done in 84.1% of patients. At 10 years, the cumulative incidence of locoregional relapse was 15.1%. In multivariate analysis, regional lymph node involvement (≥4 nodes) was associated with worse locoregional control (hazard ratio, 1.68; 95% confidence interval, 1.06-2.67; P = .03) and overall survival (hazard ratio, 2.16; 95% confidence interval, 1.59-2.95; P < .001). The toxicities were acceptable. The incidence of cardiac disorders (3.3%), and symptomatic lung fibrosis (1.5%) was low during follow-up. At 10 years, the cumulative rate of arm lymphedema was 9.5% and considered severe in 20 patients (4.4%). CONCLUSIONS: The long-term results of this study show that HFRT-PM of 26 Gy in 6 fractions over 5 weeks seems safe, but locoregional recurrence seems slightly higher than that observed in the literature, highlighting the need for long-term follow-up and for randomized trials for hypofractionated radiation therapy postmastectomy.

Effect of lockdown on digestive system cancer care amongst older patients during the first wave of COVID-19: The CADIGCOVAGE multicentre cohort study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had a dramatic impact on cancer diagnosis and treatment. Most patients newly diagnosed with digestive system cancer are aged 65 and over. METHODS: We performed a retrospective, observational, multicentre cohort study based on prospectively collected electronic health records. All adults aged 65 or over and having been newly treated for a digestive system cancer between January 2018 until August 2020 were enroled. RESULTS: Data on 7882 patients were analysed. The first COVID-19 lockdown period led to a 42.4% decrease in newly treated digestive system cancers, and the post-lockdown period was associated with a 17% decrease. The decrease in newly treated digestive system cancer did not differ as a function of age, sex, comorbidities, primary tumour site, and disease stage. The proportion of patients admitted to an emergency department increased during the lockdown period. We do not observe a higher 3-month mortality rate in 2020, relative to the corresponding calendar periods in 2018 and 2019. CONCLUSION: To avoid a decrease in newly treated cancers during future lockdown periods, access to healthcare will have to be modified. Although 3-month mortality did not increase in any of the patient subgroups, the 2020 cohort must be followed up for long-term mortality.

Intraoperative Radiotherapy for Breast Cancer in Elderly Women.

PURPOSE: To evaluate outcomes and postoperative toxicities after intraoperative radiotherapy (IORT) in elderly women. POPULATION: Women older than 65 years, with infiltrating ductal breast cancer ≤3 cm, expressing estrogen receptor (ER+) without Her2 overexpression, and with negative axillary nodes. TREATMENT: Treatment consisted of partial mastectomy with a sentinel lymph node biopsy (SLNB) procedure; in case of positive SLNB, IORT was cancelled. IORT consisted in a total dose of 20 Gy in 1 fraction delivered at the surface of the applicator with the Intrabeam® technique. RESULTS: IORT was planned to be administered to a total of 225 patients but was cancelled for 34 patients during surgery. Thus 191 patients were analyzed; mean age was 76 years, with 57 patients (30%) >80 years. Despite inclusion criteria, 15 had lobular carcinoma and 7 were triple negative. With a median follow-up of 40 months, we observed only 1 local recurrence, located in the skin over the initial tumor. The 5-year local relapse rate was 1.7%. A wound healing delay (>15 days) was observed in 21 patients (11%). Sixty-six patients (35%) had postoperative complications, mainly grade 2, resolving within a few days. Two patients needed surgical drainage for local abscesses. Long-term (>1 year) cosmetic outcome was evaluated in 120 patients and was judged excellent or good in 102 (91%). CONCLUSION: IORT can be safely given to elderly women, with a good local control rate and without major toxicities.

Phase II INTERACT-ION study: ezabenlimab (BI 754091) and mDCF (docetaxel, cisplatin, and 5-fluorouracil) followed by chemoradiotherapy in patients with Stage III squamous cell anal carcinoma.

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 involved-node 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. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04719988, identifier NCT04719988.