Prognostic Factors of Long-Term Outcomes after Primary Chemo-Radiotherapy in Non-Metastatic Anal Squamous Cell Carcinoma: An International Bicentric Cohort

Anal squamous cell carcinoma (ASCC) is a rare malignancy with a rising incidence associated with human papillomavirus (HPV) infection. The locally advanced disease is associated with a 30% rate of treatment failure after standard chemoradiotherapy (CRT). We aimed to elucidate the prognostic factors for ASCC after curative CRT. A retrospective multicenter study of 176 consecutive patients with ASCC having completed CRT treated between 2010 and 2017 at two centers was performed. Complete response (CR), disease-free survival (DFS), and overall survival (OS) were analyzed by Kaplan–Meier estimates with log-rank tests. The hierarchical clustering on principal components (HCPC) method was employed in an unsupervised and multivariate approach. The CR rate was 70% and was predictive of DFS (p < 0.0001) and OS (p < 0.0001), where non-CR cases were associated with shorter DFS (HR = 16.5, 95% CI 8.19–33.21) and OS (HR = 8.42, 95% CI 3.77–18.81) in a univariate analysis. The median follow-up was 38 months, with a 3-year DFS of 71%. The prognostic factors for DFS were cT1-T2 (p = 0.0002), N0 (p = 0.035), HIV-positive (p = 0.047), HIV-HPV coinfection (p = 0.018), and well-differentiated tumors (p = 0.037). The three-year OS was 81.6%. Female sex (p = 0.05), cT1-T2 (p = 0.02) and well-differentiated tumors (p = 0.003) were associated with better OS. The unsupervised analysis demonstrated a clear segregation of patients in three clusters, identifying that poor prognosis clusters associated with shorter DFS (HR = 1.74 95% CI = 1.25–2.42, p = 0.0008) were enriched with the locally advanced disease, anal canal location, HIV-HPV coinfection, and non-CR. In conclusion, our results reinforce the prognostic value of T stage, N stage, sex, differentiation status, tumor location, and HIV-HPV coinfection in ASCC after CRT.Fil: Iseas, Soledad. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Prost, Diego. Inserm; FranciaFil: Bouchereau, Sarah. Paris-St Joseph Hospital; FranciaFil: Golubicki, Mariano. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Robbio, Juan. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Oviedo, Ana. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Coraglio, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Kujaruk, Mirta. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Méndez, Guillermo. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Carballido, Marcela. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Roca, Enrique. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Gros, Louis. Paris-St Joseph Hospital; FranciaFil: De Parades, Vincent. Paris-St Joseph Hospital; FranciaFil: Baba Hamed, Nabil. Paris-St Joseph Hospital; FranciaFil: Adam, Julien. Paris-St Joseph Hospital; FranciaFil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Raymond, Eric. Paris-St Joseph Hospital; Franci

Unraveling Emerging Anal Cancer Clinical Biomarkers from Current Immuno-Oncogenomics Advances

Anal squamous cell carcinoma (ASCC) is a rare gastrointestinal malignancy associated with high-risk human papillomavirus (HPV) and is currently one of the fastest-growing causes of cancer incidence and mortality in developed countries. Although next-generation sequencing technologies (NGS) have revolutionized cancer and immuno-genomic research in various tumor types, a limited amount of clinical research has been developed to investigate the expression and the functional characterization of genomic data in ASCC. Herein, we comprehensively assess recent advancements in "omics" research, including a systematic analysis of genome-based studies, aiming to identify the most relevant ASCC cancer driver gene expressions and their associated signaling pathways. We also highlight the most significant biomarkers associated with anal cancer progression, gene expression of potential diagnostic biomarkers, expression of therapeutic drug targets, and emerging treatment opportunities. This review stresses the urgent need for developing target-specific therapies in ASCC. By illuminating the molecular characteristics and drug-target expression in ASCC, this study aims to provide insights for the development of precision medicine in anal cancer.Fil: Iseas, Soledad. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Golubicki, Mariano. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Gros, Louis. Paris-St Joseph Hospital; FranciaFil: Baba Hamed, Nabil. Paris-St Joseph Hospital; FranciaFil: De Parades, Vincent. Paris-St Joseph Hospital; FranciaFil: Adam, Julien. Paris-St Joseph Hospital; FranciaFil: Raymond, Eric. Paris-St Joseph Hospital; FranciaFil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin

Prognostic Factors of Long-Term Outcomes after Primary Chemo-Radiotherapy in Non-Metastatic Anal Squamous Cell Carcinoma: An International Bicentric Cohort

Anal squamous cell carcinoma (ASCC) is a rare malignancy with a rising incidence associated with human papillomavirus (HPV) infection. The locally advanced disease is associated with a 30% rate of treatment failure after standard chemoradiotherapy (CRT). We aimed to elucidate the prognostic factors for ASCC after curative CRT. A retrospective multicenter study of 176 consecutive patients with ASCC having completed CRT treated between 2010 and 2017 at two centers was performed. Complete response (CR), disease-free survival (DFS), and overall survival (OS) were analyzed by Kaplan–Meier estimates with log-rank tests. The hierarchical clustering on principal components (HCPC) method was employed in an unsupervised and multivariate approach. The CR rate was 70% and was predictive of DFS (p &lt; 0.0001) and OS (p &lt; 0.0001), where non-CR cases were associated with shorter DFS (HR = 16.5, 95% CI 8.19–33.21) and OS (HR = 8.42, 95% CI 3.77–18.81) in a univariate analysis. The median follow-up was 38 months, with a 3-year DFS of 71%. The prognostic factors for DFS were cT1-T2 (p = 0.0002), N0 (p = 0.035), HIV-positive (p = 0.047), HIV-HPV coinfection (p = 0.018), and well-differentiated tumors (p = 0.037). The three-year OS was 81.6%. Female sex (p = 0.05), cT1-T2 (p = 0.02) and well-differentiated tumors (p = 0.003) were associated with better OS. The unsupervised analysis demonstrated a clear segregation of patients in three clusters, identifying that poor prognosis clusters associated with shorter DFS (HR = 1.74 95% CI = 1.25–2.42, p = 0.0008) were enriched with the locally advanced disease, anal canal location, HIV-HPV coinfection, and non-CR. In conclusion, our results reinforce the prognostic value of T stage, N stage, sex, differentiation status, tumor location, and HIV-HPV coinfection in ASCC after CRT.</jats:p

Prognostic Factors of Long-Term Outcomes after Primary Chemo-Radiotherapy in Non-Metastatic Anal Squamous Cell Carcinoma: An International Bicentric Cohort

Anal squamous cell carcinoma (ASCC) is a rare malignancy with a rising incidence associated with human papillomavirus (HPV) infection. The locally advanced disease is associated with a 30% rate of treatment failure after standard chemoradiotherapy (CRT). We aimed to elucidate the prognostic factors for ASCC after curative CRT. A retrospective multicenter study of 176 consecutive patients with ASCC having completed CRT treated between 2010 and 2017 at two centers was performed. Complete response (CR), disease-free survival (DFS), and overall survival (OS) were analyzed by Kaplan&ndash;Meier estimates with log-rank tests. The hierarchical clustering on principal components (HCPC) method was employed in an unsupervised and multivariate approach. The CR rate was 70% and was predictive of DFS (p &lt; 0.0001) and OS (p &lt; 0.0001), where non-CR cases were associated with shorter DFS (HR = 16.5, 95% CI 8.19&ndash;33.21) and OS (HR = 8.42, 95% CI 3.77&ndash;18.81) in a univariate analysis. The median follow-up was 38 months, with a 3-year DFS of 71%. The prognostic factors for DFS were cT1-T2 (p = 0.0002), N0 (p = 0.035), HIV-positive (p = 0.047), HIV-HPV coinfection (p = 0.018), and well-differentiated tumors (p = 0.037). The three-year OS was 81.6%. Female sex (p = 0.05), cT1-T2 (p = 0.02) and well-differentiated tumors (p = 0.003) were associated with better OS. The unsupervised analysis demonstrated a clear segregation of patients in three clusters, identifying that poor prognosis clusters associated with shorter DFS (HR = 1.74 95% CI = 1.25&ndash;2.42, p = 0.0008) were enriched with the locally advanced disease, anal canal location, HIV-HPV coinfection, and non-CR. In conclusion, our results reinforce the prognostic value of T stage, N stage, sex, differentiation status, tumor location, and HIV-HPV coinfection in ASCC after CRT

Performance of 18FDG-PET in the management of non-metastatic HIV+ anal squamous cell carcinoma (ASCC).

541 Background: ASCC remains rare, but the incidence has been increasing over the last decade, especially in patients with HIV infection (HIV+). A recent meta-analysis demonstrated the usefulness of 18FDG-PET in initial staging and response assessment in ASCC. HIV+ patients may develop opportunistic infections which can cause false positives lymph nodes on PET scanning and, therefore, our objective was to evaluate performance of 18FDG-PET in HIV+ patients. Methods: Retrospective analysis of consecutive patients with non-metastatic ASCC, treated in our institution during six years. HIV+ patients were analyzed separately in two groups according to their lymph nodes status, group 1 (Gr 1): N0, group 2 (Gr 2): N1, N2, N3. Results: A total of 87 patients with ASCC were analyzed, including 24 HIV+ patients (21 males, median age was 53 for male and 50 for women). There were 15 patients in Gr 1 and 9 in Gr 2. All patients performed conventional imaging (MRI and CT-scan). In Gr 1, 12/15 patients had 18FDG-PET, it resulted in upstaging nodal disease in 2 patients. In Gr 2, 6/9 patients had 18FDG-PET, it resulted in upstaging nodal disease in 1 patient and downstaging nodal disease in 2 patients. Both of sensibility and specificity of FDG-PET were 83% in our HIV+ population. All patients underwent Mitomycine C and 5FU based chemoradiation or exclusive radiation therapy. Mean radiation dose received was 63.3Gy in G1 and 63.9Gy in G2. 18FDG-PET drives a modification in treatment strategy in only 1 patient in both of groups. Post-treatment 18FDG-PET was performed 4 months after treatment completion. Among patients who had post-treatment 18FDG-PET, a metabolic complete response was observed in 6/11 patients in Gr 1 and 3/5 patients in Gr 2. Survival at 5 years was 89% and 75% in Gr 1 and Gr 2, respectively. Conclusions: Based on our experience, 18FDG-PET drives substantial changes neither in staging nor in therapeutic strategy for ASCC HIV+ patients, however, it may be useful for radiation therapy planning. </jats:p

What is the optimal treatment for T1N0 anal squamous cell carcinoma? Analysis of current practices in the prospective French FFCD ANABASE cohort

International audienceIntroduction: for localized T1N0 squamous cell carcinoma of the anus (SCCA) standard radiotherapy (RT) may result in overtreatment and alternative strategies are debated. Methods: T1N0M0 SCCA treated between 2015 and 2020 by local excision (LE) or RT were analyzed from the French prospective FFCD ANABASE cohort. Treatment strategies, recurrence-free and colostomy-free survivals (RFS, CFS) and prognostic factors were reported. Results: among 1135 SCCA patients, 99 T1N0M0 were treated by LE(n = 17,17.2%), or RT ( n = 82,82.8%) including RT alone ( n = 65,79.2%) or chemo-RT ( n = 17, 20.7%). Median follow-up was 27.2 months [0.03 and ndash;54.44]. Median tumor size were 11.4 mm [0.9 and ndash;20] and 15.3 mm [2 and ndash;20] in the LE and RT groups respectively. Mean RT tumor dose was 59.4 Gy [18 and ndash;69.4 Gy]. One patient in LE group and 9 in RT group had a pelvic recurrence, either local (60%), nodal (10%) or both (30%). RFS and CFS at 24 months were 92.2%[95%CI,83.4 and ndash;96.4] and 94.6%[95%CI,86.1 and ndash;98.0], at 36 months 88.1%[95%CI,77.1 and ndash; 94.2] and 88.5%[95%CI,77.0 and ndash;94.5], in LE and RT group respectively, without any significative difference (HR = 0.57;[95%CI,0.07 and ndash;4.45];p= 0.60). By univariate analysis, male gender was the only prognostic fac-tor(HR = 5.57;95%CI, 1.76 and ndash;17.63; p = 0.004). Conclusion: this cohort confirms the heterogeneity of T1N0M0 SCCA management, questioning the place of RT alone, reduced dose or RT volume, and the safety of LE. (c) 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved

Abstract 2734: Impact of circulating and tissue biomarkers in patients with metastatic colorectal cancer treated with first-line FOLFOX-aflibercept therapy. Results of the GERCOR VELVET Phase II Study

Abstract Background: The combination of aflibercept to OPTIMOX (VELVET study) was evaluated in patients with previously untreated advanced colorectal cancer. A biomarker program was set-up to explore the expression of several tissue biomarkers at baseline and circulating biomarkers upon treatment cycles to identify the best monitoring biomarkers of the treatment strategy. Methods: VELVET was a prospective, single arm phase II trial. Patient’s plasma samples were collected at baseline, and during induction therapy at day 1 of the first 6 cycles. Circulating biomarkers were analyzed using multiplexing immunoassays (31 biomarkers, 3 panels). Assays were conducted on a Biorad Bioplex platform, expect for PlGF, VEGF-A and Neuropillin-1 which were assessed using ELISA assays. Tissue biomarker were analyzed at baseline by IHC, using a BOND-Max autostainer (Leica biosystems). EGFR mutation status were analyzed using next generation sequencing. Results: Among 49 patients included in the VELVET study from May 2013 to May 2014, 44 (90%) patients were evaluable for circulating biomarkers expression. The proportion of patients with tumor response (CR or PR) was higher in patients with high baseline levels of sVEGFR2, sEGFR, G-CSF, Prolactin and low baseline levels of VEGFA and MIF. Progression-free survival (PFS) was higher in patients with low baseline levels of Osteopontin (HR: 0.53; P=0.045) and in patients with high baseline levels of VEGF-C (HR: 0.45; P=0.014) and sVEGFR3 (HR: 0.50; P=0.045). Overall survival was higher in patients with high sVEGFR3 (HR: 0.36; P=0.030) levels. In both responders and non-responders, sVEGFR-1 and PlGF dramatically increased upon exposure to aflibercept and remained overexpressed for the all course of induction therapy. Circulation biomarkers modulations will be analyzed upon the 6 cycles. Tumor tissue biomarker assessment at baseline using IHC and theEGFR pathway mutations status will be added. Conclusions: Exposure to aflibercept is associated with an increase of sVEGFR-1 and PlGF at cycle 1. Elevated baseline expression levels of on-target sVEGFR3 predict favorable outcome in patients treated with aflibercept. Citation Format: Annemilai Tijeras-Raballand, Armand de Gramont, Marielle Chiron, Jean-Baptiste Bachet, Thierry Andre, Dominique Auby, Jerome Desramé, Baba-Hamed Nabil, Lecaille Cedric, Valérie Lebrun, Christophe Louvet, Annette Larsen, Christophe Tournigand, Sylvie Benner, Malika Attia, Aimery de Gramont, Franck Bonnetain, Benoist Chibaudel. Impact of circulating and tissue biomarkers in patients with metastatic colorectal cancer treated with first-line FOLFOX-aflibercept therapy. Results of the GERCOR VELVET Phase II Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2734. doi:10.1158/1538-7445.AM2017-2734</jats:p