Metastatic Anal Squamous Cell Carcinoma Research Articles

Systematic review of survival following liver or lung metastasectomy for metastatic anal squamous cell carcinoma.

Metastatic anal squamous cell carcinoma (SCC) carries a poor prognosis and the evidence base for surgical resection of metastases remains limited. The aim of this study was to establish the survival outcomes for patients undergoing metastasectomy for anal SCC. A systematic review was performed using the MEDLINE®, Embase®, Cochrane and PubMed® databases. Studies were considered for inclusion in the review if they involved patients aged >18 years with a diagnosis of stageIV anal SCC who underwent metastasectomy for liver and/or lung metastases. The primary outcome measure was overall survival. Secondary outcome measures were disease free survival, early morbidity according to the Clavien-Dindo classification and quality of life, measured using a validated scoring tool. Risk of bias was assessed with the ROBINS-I (Risk Of Bias In Non-randomised Studies - of Interventions) tool. There were 10 studies with a total of 98 patients. There was heterogeneity in results reporting, with recurrence free survival the most reported outcome. For all studies reporting on liver metastasectomy, the one-year overall survival rate was 87%. In studies with adequate follow-up reported, the three and five-year overall survival rates were 53% and 38% respectively. Only one study reported on lung metastasectomy patients; the overall median survival was 24 months. None of the studies reported on quality of life measures. The ROBINS-I tool identified a critical risk of bias in six studies, a serious risk in one study and a moderate risk in three studies. The evidence base for metastasectomy in metastatic anal SCC is limited. Further information is required to inform future treatment methods and use of a standardised outcomes reporting method is needed to support this.

557MO Phase II trial evaluating the efficacy of pembrolizumab combined with vorinostat in patients with recurrent and/or metastatic anal squamous cell carcinoma: Subgroup analysis of the PEVOsq basket trial

557MO Phase II trial evaluating the efficacy of pembrolizumab combined with vorinostat in patients with recurrent and/or metastatic anal squamous cell carcinoma: Subgroup analysis of the PEVOsq basket trial

Role of local therapy in the management of patients with metastatic anal squamous cell carcinoma: a National Cancer Database study.

About 10-20% of patients with anal squamous cell carcinoma (SCCa) present with metastatic disease and are usually treated with systemic chemotherapy. However, primary tumor control is crucial as local failure is associated with significant morbidity. Using the largest cohort to date, we report the impact of local therapy on survival among patients with metastatic anal SCCa. Data were collected from US hospitals that contributed to the National Cancer Database (NCDB) between 2004 and 2015. Patients who did not receive palliative systemic chemotherapy were excluded from analysis. Univariate (UVA) and multivariable analyses (MVA) were performed to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used to evaluate the association between tumor/patient characteristics and overall survival (OS). A total of 1,160 patients were identified over the 12 years of study. Median age was 57 years. Majority were female (64.9%), non-Hispanic Whites (79.1%) and had Charlson-Deyo Score of 0 (83.6%). Most common metastatic sites were liver (25.9%), lung (11.6%) and bone (8.5%). More than 79% of the patients had received radiation to the primary site, and 10.4% underwent surgical resection for local control. Use of local therapy correlated closely with OS on MVA (HR 0.66; 0.55-0.79; P<0.001), with a 12-month and 5-year OS rates of 72.8% and 25.7% respectively, compared with 61.1% and 14.6% for patients treated with chemotherapy only. Poor prognostic factors included male gender (HR 1.44; 1.24-1.67; P<0.001), age >70 years (HR 1.28; 1.02-1.62; P=0.034), lack of health insurance (HR 1.32; 1.02-1.71; P=0.034), and cloacogenic zone location (HR 4.02; 1.43-11.30; P=0.008). There was no benefit from abdominoperineal resection (mOS =19.7 months; HR 1.05; 0.48-2.29; P=0.909), but both local resection of the primary (mOS =24.8 months, HR 0.48; 0.29-0.80; P=0.005) and palliative radiation (mOS =22.6 months; HR 0.66; 0.55-0.79; P<0.001) were associated with improved OS. In addition to systemic therapy, resection of the primary tumor or palliative radiation improved OS in patients with anal SCCa. Patients unlikely to benefit from local control were those >70 years of age, male, lack of health insurance and cloacogenic carcinoma.

Stage IV anal canal squamous cell carcinoma with long-term survival: a case report

BackgroundCurrently, no established standard treatment exists for metastatic anal squamous cell carcinoma. We report a case of complete response in a patient with stage IV anal squamous cell carcinoma after undergoing multidisciplinary treatment.Case presentationA 62-year-old woman visited a nearby doctor with a chief concern of severe pain associated with a firm mass in the anus. The patient was diagnosed with anal canal squamous cell carcinoma and liver metastases and referred to First Department of Surgery Faculty of Medicine University of Fukui for treatment. The patient received a TNM classification of T4N0M1 and stage IV. Rectal amputation was performed; however, postoperative complications hindered immediate anticancer therapy and the liver metastases exacerbated. Radiofrequency hyperthermia and systemic chemotherapy were performed 3 months postoperatively. A prominent reduction in the liver metastasis was observed. Lung metastases appeared during the course of systemic chemotherapy. Radiotherapy was performed to treat the lung lesion and resolved. Radiotherapy was also performed for liver metastasis. The lesion in the liver showed resolution after 54 months postoperatively, and treatment with the anticancer drug was discontinued. Ten-year follow-up findings suggested complete resolution of the lesion in response to the treatment protocol followed in this case. This long-term survival was achieved through a multidisciplinary treatment.ConclusionsThe present case suggests that multidisciplinary treatment approach is effective for resolving stage IV anal squamous cell carcinoma, and addition of new anticancer drug therapy may improve the overall prognosis of squamous cell carcinoma.

Impact of local therapy on survival among patients with metastatic anal squamous cell carcinoma.

4 Background: About 10-20% of patients with anal squamous cell carcinoma (SCCa) present with metastatic disease, and are usually treated with systemic chemotherapy. The role of local therapy to control the primary tumor is controversial in this setting. We evaluated survival impact of local therapy in metastatic anal SCCa. Methods: Data were obtained from all US hospitals that contributed to the National Cancer Database (NCDB) between 2004 and 2015. We excluded patients who did not receive palliative systemic chemotherapy. Univariate (UVA) and multivariable analyses (MVA) were performed to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used to assess the association between tumor/patient characteristics and overall survival (OS). Results: 1,160 patients were identified over 12 years. Median age was 57 years. Majority were female (64.9%), non-Hispanic Whites (79.1%) and had Charlson-Deyo Score of 0 (83.6%). Most common metastatic sites were liver (25.9%), lung (11.6%) and bone (8.5%). More than 79% of the patients received radiation to the primary site, and 10.4% underwent surgical resection for local control. Use of local therapy correlated closely with a significant improvement in OS on MVA (HR 0.66; 0.55-0.79; p &lt; 0.001), with a 12-month and 5-year OS rates of 72.8% and 25.7% respectively, compared with 61.1% and 14.6% for patients treated with chemotherapy only. Poor prognostic factors included male gender (HR 1.44; 1.24-1.67; p &lt; 0.001), age &gt; 70 years (HR 1.28; 1.02-1.62; p = 0.034), lack of health insurance (HR 1.32; 1.02-1.71; p = 0.034), and cloacogenic zone location (HR 4.02; 1.43-11.30; p = 0.008). There was no benefit from abdominoperineal resection (mOS = 19.7mos; HR 1.05; 0.48-2.29; p = 0.909), but both local resection of the primary (mOS = 24.8mos, HR 0.48; 0.29-0.80; p = 0.005) and palliative radiation (mOS = 22.6 mos; HR 0.66; 0.55-0.79; p &lt; 0.001) were associated with improved OS. Conclusions: This is the largest reported study on management of de novo stage IV SCCa. The data suggest that local control of the primary tumor through resection or radiation improved OS in patients with anal SCCa. Patients unlikely to benefit from local therapy include age over 70 years, male, lack of health insurance and cloacogenic carcinoma.

Circulating tumor DNA-based molecular residual disease detection and recurrence monitoring in patients with advanced or metastatic anal squamous cell carcinoma.

6 Background: For patients with anal squamous cell carcinoma (ASCC), the current standard of care involves curative-intent definitive chemoradiation. For those that recur locally, salvage surgery maybe a consideration. ASCC, however, still lacks a non-invasive blood-based biomarker, which can be of value in this patient population for monitoring recurrence and/or response to immunotherapy later. Circulating tumor DNA (ctDNA) is a promising non-invasive tool to assess molecular residual disease (MRD) and recurrence in ASCC. Here, we evaluated real-world utility of ctDNA status to identify MRD and recurrence in ASCC patients across all stages. Methods: This is a retrospective analysis of patients with any stage ASCC receiving SOC or/and immunotherapy with immune checkpoint inhibitors. A personalized tumor-informed PCR/NGS-based assay (Signatera) was used for ctDNA detection, in the pre/on/post-treatment and surveillance setting. Results: In this study, plasma samples (n=105) were collected from 25 ASCC patients (13 females, 12 males; median age 66 years) at various timepoints for a median follow-up of 315 days (range: 59-1717), post-diagnosis; 12 patients were HPV-positive, 1 patient was HPV-negative, and 12 had unknown HPV status; 88% (22/25) of the patients had serial timepoints (≥2) available. ctDNA-positivity rates, test results, and ctDNA quantification by stage are summarized in Table. The quantitated ctDNA values (mean tumor molecules (MTM)/mL) increased in concordance with the stage of the disease, with values trending higher in stage III and IV. In addition, complete clinical outcome information was available for 22/25 patients at the time of releasing this data. Of the 96 plasma samples drawn from these patients, 68 (70%) were in the surveillance setting (post-definitive therapy). No recurrences were observed among 15 patients who cleared ctDNA on treatment and/or tested negative post-treatment, whereas, 6/7 ctDNA-positive patients were confirmed to have disease recurrence and 1 was pending confirmatory imaging. This often predated recurrence on scans. Conclusions: Measuring and monitoring MRD in patients with ASCC is feasible and has the potential to impact clinical decision making. Our study is the first to set the benchmark for the feasibility of using a tumor-informed assay in ASCC. Larger prospective studies are needed to explore the clinical utility of ctDNA status to guide disease surveillance and management of ASCC.[Table: see text]

Pembrolizumab for previously treated advanced anal squamous cell carcinoma: results from the non-randomised, multicohort, multicentre, phase 2 KEYNOTE-158 study

Outcomes in advanced anal squamous cell carcinoma are poor, with few treatment options and controlled clinical trials. We evaluated the efficacy and safety of pembrolizumab in patients with advanced anal squamous cell carcinoma (cohort A) from the phase 2 KEYNOTE-158 study. Eligible patients enrolled in the ongoing non-randomised, multicohort, multicentre, phase 2 KEYNOTE-158 study, which was done across 38 centres worldwide, were aged 18 years or older; had histologically or cytologically confirmed advanced or metastatic anal squamous cell carcinoma; had previous failure of or intolerance to standard therapy or no standard therapy options; and had a PD-L1-evaluable tissue sample. Patients received pembrolizumab 200 mg intravenously every 3 weeks for 2 years, or until disease progression, unacceptable toxicity, investigator's decision to withdraw the patient from the study, or withdrawal of patient consent. The primary endpoint was objective response, as assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Efficacy and safety analyses included all patients who received at least one dose of pembrolizumab. The trial is registered with ClinicalTrials.gov, NCT02628067. Between March 3, 2016, and July 23, 2018, 163 patients were screened, of whom 112 were enrolled and treated in the anal cancer cohort. 91 (81%) patients were female, 104 (93%) had M1 disease, and 75 (67%) had PD-L1-positive tumours. The median time from first dose to data cutoff (June 27, 2019) was 34·7 months (IQR 32·5-36·4). 12 (11%, 95% CI 6-18) patients had an objective response, including 11 (15%, 8-25) of 75 patients with PD-L1-positive tumours and one (3%; 0-17) of 30 patients with PD-L1-negative tumours. 68 (61%) patients had treatment-related adverse events (20 [18%] patients had grade 3-4 adverse events), the most common of which were fatigue (17 patients), diarrhoea (13), hypothyroidism (13), and nausea (13). Serious treatment-related adverse events occurred in 12 (11%) patients. 25 (22%) patients had immune-mediated adverse events, and one (1%) had an infusion reaction. There were no treatment-related deaths. Pembrolizumab monotherapy is a possible treatment option with a favourable benefit-risk ratio for patients with previously treated advanced anal squamous cell carcinoma who have no alternative satisfactory treatment options. Merck Sharp & Dohme.

Anal Squamous Cell Carcinoma in Ulcerative Colitis: Can Pouches Withstand Traditional Treatment Protocols?

Anal squamous cell carcinoma has rarely been reported in the setting of ulcerative colitis. This study aimed to understand the prognosis of anal squamous cell carcinoma in the setting of ulcerative colitis. This is a retrospective review. This study was conducted at a referral center. Adult patients with both ulcerative colitis (556.9/K51.9) and anal squamous cell carcinoma (154.3/C44.520) between January 1, 2000 and August 1, 2019 were included. The primary outcomes measured are treatment and survival of anal squamous cell carcinoma. Of the 13,499 patients with ulcerative colitis treated, 17 adult patients with ulcerative colitis and anal dysplasia and/or anal squamous cell carcinoma were included in the study: 6 had a diagnosis of anal squamous cell carcinoma, 8 had high-grade squamous intraepithelial lesions, and 3 had low-grade squamous intraepithelial lesions. There were 4 men (23%) and a median age of 55 years (range, 32-69) years. At diagnosis, 6 had an IPAA, of which 5 had active pouchitis, 1 had an ileorectal anastomosis with active proctitis, 1 had a Hartmann stump with disuse proctitis, 5 had pancolitis, and 4 had left-sided colitis. Of the 6 with anal squamous cell carcinoma, all received 5-fluorouracil and mitomycin C with external beam radiation therapy. Four patients had an IPAA, all of whom required intestinal diversion or pouch excision because of treatment intolerance. At a median follow-up of 60 months, 3 patients died: one at 0 months (treatment-related myocardial infarction), one at 60 months (metastatic anal squamous cell carcinoma), and one at 129 months (malignant peripheral nerve sheath tumor); the remaining patients had no residual disease. This study was limited because of its retrospective nature and small number of patients. Anal squamous cell carcinoma in the setting of ulcerative colitis is extremely rare. In the setting of IPAA, diversion may be necessary to prevent radiation intolerance. Careful examination of the perianal region should be performed at the time of surveillance endoscopy. See Video Abstract at http://links.lww.com/DCR/B582. ANTECEDENTES:La incidencia de cáncer anal de células escamosas es muy baja en pacientes con colitis ulcerosa.OBJETIVO:Comprender el pronóstico del cáncer anal de células escamosas en el contexto de la colitis ulcerosa.DISEÑO:Revisión retrospectiva.AJUSTE:Centro de referencia.PACIENTES:Pacientes adultos con colitis ulcerosa (556.9 / K51.9) y cáncer anal de células escamosas (154.3 / C44.520) entre el 1 de enero de 2000 y el 1 de agosto de 2019.RESULTADOS PRINCIPALES:Tratamiento y sobrevida del cáncer anal de células escamosas.RESULTADOS:De 13.499 pacientes en tratamiento por colitis ulcerosa, diecisiete presentaron displasia y/o cáncer de células escamosas: 6 con cáncer, 8 con lesiones intraepiteliales escamosas con displasia de alto grado y 3 con displasia de bajo grado.Cuatro son hombres (23 %) con una mediana de 55 años (rango 32-69). Al realizar el diagnóstico 6 tenían pouch, 5 con pouchitis activa; 1 con ileorecto anastomosis con proctitis activa y 1 con operación de Hartman y muñón con colitis por desuso; además 5 tenían pancolitis y 4 tenían colitis izquierdaTodos los casos con cáncer anal de células escamosas (6 pacientes), fueron tratados con 5-FU mas Mitomicina y radioterapia externa. Cuatro pacientes tenían pouch, todos requirieron derivación intestinal o escisión del pouch por intolerancia al tratamiento.En la mediana de seguimiento de 60 meses, tres pacientes fallecieron: uno a los 0 meses (infarto de miocardio relacionado con el tratamiento), uno a los 60 meses (cáncer de células escamosas metastásico) y uno a los 129 meses (tumor maligno de la vaina del nervio periférico); el resto no presentaba enfermedad residual.LIMITACIONES:Revisión retrospectiva, número pequeño de pacientes.CONCLUSIÓN:El cáncer anal de células escamosas en el contexto de la colitis ulcerosa es extremadamente raro. En el contexto de IPAA, la derivación puede ser necesaria para prevenir la intolerancia a la radiación. Se debe realizar un examen cuidadoso de la región perianal en el momento de la endoscopia de control. Consulte Video Resumen en http://links.lww.com/DCR/B582.

The impact of gender and HPV status on anal squamous cell carcinoma survival.

Anal cancer is a rare entity and the effect of gender and HPV status on survival is controversial. We aimed to evaluate the difference in overall survival (OS) according to gender and analyzed the effect of HPV status on OS. The National Cancer Database (NCDB) was queried for patients with anal squamous cell carcinoma between 2004 and 2016. We evaluated the OS based on gender and HPV status using Kaplan-Meier estimates and we used multivariate Cox regression analyses to evaluate factors associated with overall survival. A total of 6133 patients with known HPV status were included for analysis. In the non-metastatic group, male gender was associated with worse OS (HR 1.50, 95% CI 1.32-1.70; P<0.001) whereas HPV status did not affect the OS (HR 1.08, 95% CI 0.96-1.22; P=0.213). In the metastatic group, there was no difference in OS based on gender (HR 1.29, 95% CI 0.91-1.82; P=0.148), whereas HPV-negative status was associated with worse OS (HR 1.52, 95% CI 1.09-2.12; P=0.014). Females had better OS only in non-metastatic anal squamous cell carcinoma (ASCC). HPV-negative status was associated with worse OS only in metastatic ASCC.

Episomal HPV16 responsible for aggressive and deadly metastatic anal squamous cell carcinoma evidenced in peripheral blood

Archival tissue samples collected longitudinally from a patient who died from HPV16-induced high-grade anal intraepithelial squamous cell carcinoma with vertebral HPV16–positive metastasis were retrospectively analyzed by the Capture-HPV method (Capt-HPV) followed by Next-Generation Sequencing (NGS). Full length nucleotide sequences of the same HPV16 were identified from the initial and second anal biopsy samples, from plasma sample and from vertebral metastasis biopsy. Remarkably, HPV was episomal in each sample. The HPV genome sequence was closest to the HPV16 Qv18158E variant subtype (A1 lineage) exhibiting base substitutions and deletions in 7 and 2 HPV loci, respectively. In conclusion, the powerful Capt-HPV followed by NGS allows evidencing the detailed cartography of tumoral and circulating HPV DNA, giving rise to a unique and unexpected episomal virus molecular status in a context of aggressive carcinoma, underlying the importance of HPV status and its association with clinical features for further prospective studies.

Definitive Intent Locoregional IMRT In Oligometastatic Anal Squamous Cell Carcinoma

The role of locoregional intensity modulated radiation therapy (IMRT) in patients with metastatic anal squamous cell carcinoma (SCC) remains undefined. There is growing evidence of the potential benefit of local therapy even in the setting of oligometastatic disease to prevent the morbidity of uncontrolled pelvic disease. We queried an institutional database of 358 consecutive patients with SCC of the anal canal treated with definitive intent pelvic IMRT from 2005 to 2018 to identify patients with de novo metastatic disease. Locoregional control (LRC), progression-free survival (PFS), and overall survival (OS) were computed using the Kaplan-Meier method. Acute and late toxicities were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Twenty-five patients with a median follow-up of 26 months including 19 (76%) women and 6 (24%) men with a median age of 60 years comprised the evaluable cohort. Eight (32%) patients had a solitary metastasis, 10 (40%) had two metastatic lesions, 2 (8%) had three metastatic lesions, 5 (20%) had four or more metastatic lesions. Non-regional lymph nodes were the most common site of metastatic disease (N = 16, 49%) followed by liver (N = 10, 30%), lung (N = 4, 12%), and others (N = 3, 9%). Sixteen patients had HPV related disease and 3 patients were HIV+. The median dose to the primary tumor was 56Gy (range, 50-58Gy) in a median of 28 fractions (range, 25-29) over a median of 39 elapsed days (range, 35-55). Twelve (48%) patients received induction chemotherapy and all patients received concurrent chemotherapy predominately mitomycin and capecitabine based. Twenty-one (84%) patients had metastatic-directed ablative therapy which included radiation (N = 20, 80%) and IR-ablation (N = 1, 4%). No patients underwent metastasectomy or received additional chemotherapy, targeted therapy, or immunotherapy prior to progression of disease. The 3-year LRC was 81%, PFS was 27%, and OS was 53%. In comparing patients with non-regional lymph node involvement to patients with visceral organ involvement there was no significant difference in LRC (86% vs. 79%, p = 0.950) but a trend for improved PFS (71% vs. 18%, p = 0.069) and OS (86% vs. 49%, p = 0.365). Grade 3+ acute toxicity included dermatitis (12%), proctitis (4%), and diarrhea (4%). Late grade 2+ toxicity rate was 12%. Definitive intent pelvic IMRT provides excellent locoregional control in patients with oligometastatic anal SCC. Local and extended regional nodal radiation is important to prevent the significant morbidity of uncontrollable pelvic disease given durable PFS and OS in patients with oligometastatic anal SCC.

The "Brescia panel" (Claudin-4 and BRCA-associated protein 1) in the differential diagnosis of mesotheliomas with epithelioid features versus metastatic carcinomas.

The distinction between mesothelioma with epithelioid features and metastatic carcinoma may be challenging, particularly on cytology. A novel 2-hit Claudin-4 and BRCA-associated protein 1 (BAP1) panel was investigated. The objective of this study was to determine the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the panel on cytology from pleural effusions and matched biopsies, including 49 malignant mesotheliomas on cytology with 43 matched biopsies, 49 normal/reactive mesothelial proliferations, and 49 pleural metastatic carcinomas from different primaries with 21 matched pleural biopsies. The diagnostic role of the 4 categories obtained by crossing the immunostaining results was analyzed. Claudin-4 strongly stained all metastatic carcinomas and tested completely negative in normal mesothelium, benign reactive mesothelial hyperplasia, and malignant mesothelioma. All normal and benign mesothelial proliferations and all carcinomas except 1 were immunoreactive for BAP1, whereas BAP1 loss was observed in 88% of malignant mesotheliomas. The expression of Claudin-4 alone excluded all benign and malignant mesothelial growth, consistently characterizing all metastatic carcinomas. Double negativity was evident in all malignant mesotheliomas, and double positivity was observed in all metastatic carcinomas. BAP1-positive/Claudin-4-negative status was observed only in malignant mesotheliomas and benign mesothelial proliferations. A single metastatic anal squamous cell carcinoma had BAP1-negative/Claudin-4-positive staining. Claudin-4 expression was completely specific and sensitive for metastatic carcinoma, excluding mesothelial proliferations. BAP1 staining characterized 98% of metastatic carcinomas and 100% of benign mesothelial proliferations, whereas negativity was observed almost exclusively in mesotheliomas. This 2-hit panel is probably the best compromise for differentiating malignant mesothelioma and metastatic carcinoma on either cytology or biopsy specimens.

PDL1 expression predicts therapeutic outcome in non metastatic anal squamous cell carcinoma (NMASCC).

4054 Background: NMASCC is a rising incidence disease with up to 30% of treatment failure to achieve complete response (CR) after standard chemoradiotherapy (CRT) leading to severe morbidity and death. Stage III-TNM, p53 mutations, HPV negativity, HIV infection are linked to treatment failure. We investigated the predictive/prognostic role of TNM, CR, HPV, PDL1 positivity and CD3/CD8 densities in NM-ASCC from a single institution. Methods: All 79 eligible consecutive NMASCC pts (available FFPE pre-treatment samples) seen from October-2009 to April-2019 having completed definitive CRT (50.4 Gy Pelvic Radiotherapy with Mitomycin-C 12mg/m2/IV/d1-5 / FU 1000mg/m2/d1-4 d29-32 (28%), Mitomycin-C/Capecitabine 825 mg/m2/bid (38%), Cisplatin 60 mg/m2/IV d1-29 and 5FU (34%) were analyzed. Mean age: 59 (range 26-87), 72% female, Stage III: 59%, HPV positive: 86% (HPV-16: 80%);14% HIV positive. IHC assessed by two pathologist for PD-L1 expression (ClonSP263) and CD3-CD8+ TILS densities (Clone 2GV6, Clone SP57). HPV-DNA assessed by PCR (BSGP5+/6+ multiplexed with beta-globin). Kaplan-Meier survival, CR, DFS, OS and Univariate analyses were performed using Cox proportional hazard model. Results: CR achieved within 6 months of treatment completion was 68%( 53pts). Median follow-up after treatment completion: 35 months (range 6 –149). As of February 2020, 82% (65 pts) are alive, no evidence of disease:(57%) 46 pts, recurrence rate: 26%(22 pts), cancer death: 18% (14 pts). PDL1+ tumors ( &gt; 1% positivity-CPS score): 56%, expression levels: 1-5% (57%,26p), &gt; 10%-100% (43%,19p). PDL1+ had a strong association with CR (p = 0.021); higher PDL1+ levels had 8-fold of CR-likelihood than PDL1 negative.(OR 8.50 vs. 1.12). Significative Spearman correlation between PDL1 tumors with CR and CD3-CD8 TILS density was observed (R = 0.43,p = 0.0017 and R = 0.36,p = 0.00094 respectively), albeit CD3-CD8 failed to reach significance as prognostic factors for either CR, DFS or OS. Only CR and PDL1 positive were strongly significantly associated to DFS (HR 0.10 [IC 95% 0.04-0.28] p &lt; 0.001 and HR 0.28 [IC 95% 0.11-0.73] p = 0.006) and OS (HR 0.12 [IC 95% 0.03-0.45] p &lt; 0.001 and HR 0.15 [IC 95% 0.03-0.68] p &lt; 0.004). Low prevalence of HPV negative, early tumors, HIV positive cases in our series probably impacted in statistical power for prognosis correlation. Conclusions: PDL1 positivity was the strongest predictive/prognostic factor in NM-ASCC. Alternative therapeutics options to standard CRT should be explored on poor-risk patients as HPV-negative, P53-mutated and PDL1 negative patients.

Image-guided Interstitial Brachytherapy in the Management of Metastasized Anal Squamous Cell Carcinoma.

Interstitial brachytherapy (IBT) has been shown to provide high tumor control rates in metastatic colorectal carcinoma. Our aim was to evaluate efficacy and safety of IBT in patients with metastatic anal squamous cell carcinoma (mASCC). Seven patients with a total of 38 unresectable ASCC metastases (28 liver, nine lung, one nodal metastases) were treated with computed tomographic or open magnetic resonance imaging-guided IBT using an iridium-192 source. Clinical and image-based follow-up were performed every 3 months after treatment. Local tumor control rate was 97.4% during a median follow-up of 15.2 months. Median progression-free survival was 3.3 months (range=2.5-32.6 months). Median overall survival after IBT was 25.2 months (range=6.5-51.0 months). No severe adverse events (grade 3 or more) were recorded. Image-guided IBT is a safe and particularly effective treatment in patients with mASCC and might provide a well-tolerated therapeutic option in a multidisciplinary setting.

536P - Docetaxel, cisplatin, and 5-fluorouracil (DCF) chemotherapy in the treatment of metastatic or unresectable locally recurrent anal squamous cell carcinoma: A phase II study of French interdisciplinary GERCOR and FFCD Groups (Epitopes-HPV02 study)

Background: Anal Squamous Cell Carcinoma (ASCC) is a rare disease, but its incidence is markedly increasing. To date, in advanced ASCC, no standard regimen exists. We have previously published the potential role of DCF regimen. Among 8 advanced ASCC consecutive patients who relapsed after CRT, the DCF regimen induced a complete response in 4 patients, including 3 pathological complete responses. Thus, this study was designed to confirm the interest of DCF regimen in advanced ASCC patients. Methods: A multicentre phase II trial was conducted among 25 hospitals in France. Main eligibility criteria were histologically proved unresectable locally advanced recurrent or metastatic ASCC, ECOG-PS <2, and being eligible for DCF. Patients received either 6 cycles of standard DCF or 8 cycles of modified DCF depending on age (> vs. < = 75 years-old) and ECOG-PS (0 vs. 1). The trial was set up based on a Simon’s optimal two-stage design, allowing an early futility interim analysis amid the first 21 patients. The primary endpoint was the observed PFS rate at 12months from the first DCF cycle. A PFS rate above 25% was expected. With a unilateral alpha error of 5% and a statistical power of 90%, 66 evaluable patients had to be included. Results: 66 patients were enrolled from September 2014 to January 2017. Median age was 60.05 years (range, 38-78) with female predominance (81.8%). 40 (60.6%) patients had locoregional involvement at enrolment, and the most frequent metastatic sites were liver (60.6%), distal lymph node (48.5%), and lung (36.4%). At interim analysis, 10 (47.6%) patients were progression-free at 12 months from the first DCF cycle. To date, 65 patients are assessable for response rate by investigators. The objective response rate is 87.7%, including 36.9% of complete responses. Among the first 32 patients with ≥12 months of follow-up, 15 (46.9%) patients were progression-free at 12 months. Conclusions: This first ever conducted prospective trial in front-line advanced ASCC demonstrated a high long-lasting response rate of the DCF regimen. DCF regimen should then be considered as a standard of care in this situation. Clinical trial identification: NCT02402842 Legal entity responsible for the study: University Hospital of Besancon Funding: Research grant from the University Hospital of Besançon Disclosure: All authors have declared no conflicts of interest.

Long Survival (Cure) to Cisplatin/Infusional 5-Flurouracil in Metastatic Squamous Cell Anal Cancer with Extensive Liver and Lung Metastases

Background: Metastatic anal Squamous Cell Carcinoma (SCC) is a relatively uncommon malignancy that is usually treated with palliative platinum based chemotherapy. Response rates are modest and complete responses are rare. Case Report: Here we report on a case of advanced SCC with the extensive visceral metastatic disease that has possibly been cured with chemotherapy alone. The patient has received 6 cycles of Cisplatin and 5FU and has remained in complete remission for over 7 years. Conclusion: This is the first report of a case of metastatic anal SCC that has been cured with chemotherapy and highlights the need to remain optimistic when treating patients with “palliative” chemotherapy.

Concurrent cisplatin, continuous infusion fluorouracil and radiotherapy followed by tailored consolidation treatment in non metastatic anal squamous cell carcinoma

BackgroundTo evaluate efficacy and feasibility of chemo-radiotherapy in patients with non-metastatic anal squamous-cell-cancer.MethodsTNM staged anal squamous-cell cancer patients were treated with pelvic radiotherapy concomitant to continuous infusion fluorouracil plus cisplatin for at least 2 cycles. In T3-T4 or any T - N+ tumours or in "slow-responder" cases, 1-2 chemotherapy courses were subsequently administered. Tumour assessment was performed at baseline and 6-8 weeks after radiotherapy to evaluate response.Results29 patients were enrolled: 4 males, 25 females; median age 57 years; baseline T1/T2/T3/T4 2/12/7/8; N involvement 17. Median dose pelvic radiotherapy was 59.4 Gy (range: 54-74). In 5 patients 2 chemotherapy courses, in 12 patients three and in 12 patients four courses were performed. At first evaluation, 27 CR (93.1%; 95% CI: 78% - 98%) and 2 SD were observed. Main grade (G) 3 toxic events were neutropenia (8%), diarrhoea (8%) and dermatitis (62%). Most frequent late events G3-G4 occurred in 14 patients: proctitis (5), dermatitis (4), bladder dysfunctions (2), sexual dysfunctions (9), lower extremity venous thromboses (2), dysuria (1), stenosis (1) and tenesmus (1). Five patients reported G1 leucopoenia. The rate of colostomy was 14%. After a median follow up of 42 months (range: 4-81), 20 patients are still alive without relapse and 3 died due to PD. The estimated 7-year DFS was 83.4% (C.I.: 68.3%-98.5%) and the estimated 7-year OS was 85.7% (C.I.: 70% - 100%). The 1-year and the estimated 7-year colostomy-free survivals were 85.9% (C.I.: 73.1% - 98.7%).ConclusionsConcurrent cisplatin plus fluorouracil and radiotherapy is associated with favourable local control rates and acute toxicity. Future investigations will be directed towards research into molecular biomarkers related to disease progression and resistance to chemo-radiotherapy and to the evaluation of new cytotoxic agents or targeted drugs, such as anti-epidermal growth factor receptor, concomitant to RT and to determining the role of intensity-modulated radiotherapy.