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.

Combination immune checkpoint therapy carried on despite grade 4 immune-related hepatotoxicity during treatment of metastatic melanoma: Case report and review of literature.

We report the case of a 63-year-old patient with recurrence of acral malignant melanoma after adjuvant immune checkpoint inhibitors (ICI) treatment by PEMBROLIZUMAB complicated with immune-related grade II hepatitis. Rechallenge by combination immune checkpoint (NIVOLUMAB + IPILIMUMAB) led to a relapse of the immune-related hepatitis up to a grade 3. Combination ICI therapy was carried on after introduction of corticosteroid therapy. Here, we present the outcomes of this immune-related adverse event (irAE) and a review of literature on the subject.

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.

Granocyte-colony stimulating factor (G-CSF) has significant efficacy as secondary prophylaxis of chemotherapy-induced neutropenia in patients with solid tumors: results of a prospective study.

AIM: To carry out a prospective, multicenter and observational study describing prophylactic strategies [cycle delay, dose-reduction, (G-CSF) prescription] to prevent recurrence of neutropenic events (NE) in patients with solid tumors, and identify potential predictive factors of NE recurrence. PATIENTS AND METHODS: Patients ≥18 years old with an NE in a previous chemotherapy cycle (cycle A) without G-CSF support, followed for four cycles (B to E) were included in the study. NE was defined as any neutropenia grade 1-4, febrile or not, which impacted on subsequent chemotherapy cycles (cycle delay, or reduction, or prophylactic G-CSF). RESULTS: Data of 548 patients were analyzed, 378 (69%) were female, with a mean (SD) age of 61.7 (12.3) years. WHO PS: 0-1: 88.3%, incidence of breast cancer: 40%, metastatic disease: 53.3%. Following the first NE episode, 44.5% of patients had cycle delay, 22.3% dose reduction and 466 (85%) received prophylactic G-CSF. NE recurrence rates were: 21.2% at cycle B, 18.6% at cycle C, 11.5% at cycle D and 12.9% at cycle E. G-CSF support (hazard ratio: 0.32, 0.24-0.43, p<0.001) was associated with lower NE recurrence. Pegfilgrastim seemed to offer the highest protection (hazard ratio; HR=0.23, 95% CI: 0.16-0.32; p<0.001). CONCLUSION: Secondary G-CSF prophylaxis has significant efficacy in reducing the incidence of NE and should be considered as a valuable option.

Targeting NF-kappaB activation via pharmacologic inhibition of IKK2-induced apoptosis of human acute myeloid leukemia cells.

Acute myeloid leukemia (AML) cells are characterized by a constitutive and abnormal activation of the nuclear factor-kappaB (NF-kappaB) transcription factor. This study, conducted in vitro on 18 patients, shows that targeting the IKB kinase 2 (IKK2) kinase with the specific pharmacologic inhibitor AS602868 to block NF-kappaB activation led to apoptosis of human primary AML cells. Moreover, AS602868 potentiated the apoptotic response induced by the current chemotherapeutic drugs doxorubicin, cytarabine, or etoposide (VP16). AS602868-induced cell death was associated with rupture of the mitochondrial transmembrane potential and activation of cellular caspases. NF-kappaB inhibition did not affect normal CD34+ hematopoietic precursors, suggesting that it could represent a new adjuvant strategy for AML treatment.