Genomic features of primary and recurrent anal squamous cell carcinoma.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 556-556
Author(s):  
Jonathan W Pike ◽  
Kent William Mouw ◽  
Lior Zvi Braunstein ◽  
Neil E. Martin ◽  
Harvey J. Mamon ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Mutation Rate ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Driver Mutations ◽  
Cancer Genes ◽  
Anal Squamous Cell Carcinoma ◽  
Recurrent Tumors ◽  
Recurrent Mutations

556 Background: Approximately 7000 cases of anal squamous cell carcinoma (ASCC) are diagnosed annually in the US, and the incidence is increasing. Combination chemoradiotherapy (CRT) is the standard of care for locally-advanced ASCC, and the 5-year survival rate is approximately 70%. Unlike many other tumor types, no large-scale genomic studies have been reported for anal cancer. In order to characterize the mutational landscape of ASCC and identify potential therapeutic targets, we perform comprehensive genomic analysis of a pilot cohort of ASCC cases. Methods: We performed whole exome sequencing of tumor and matched germline DNA from a pilot cohort of twelve patients with locally advanced (Stage II-IVA) ASCC cases treated at Dana-Farber Cancer Institute. All patients received concurrent chemoradiotherapy (CRT): seven ‘responders’ had complete response and no evidence of recurrence with a minimum of one year follow-up, while five ‘non-responders’ had residual or recurrent disease following CRT. For non-responders, both primary and residual/recurrent tumors were analyzed. Results: The overall mutation rate was 3.7 mutations per megabase (Mb). Recurrent mutations in several known cancer genes were observed. Five of twelve cases had a hotspot mutation in FBXW7, including 3 of the 5 non-responders. Known oncogenic mutations were also observed in PIK3CA (3 tumors) and NFE2L2/KEAP1 (3 tumors). Analysis of paired primary and recurrent samples revealed surprising examples of distinct driver mutations in clonally-related tumors. Copy number analysis revealed focal amplifications of chromosome 3q. Conclusions: This study represents one of the first genome-scale analyses in ASCC. The overall mutation rate was similar to other HPV-associated squamous cell carcinomas, and recurrent mutations in several known cancer genes were observed. Analysis of paired primary and residual/recurrent tumors revealed surprising heterogeneity. To extend our findings, we are currently performing a similar analysis in a larger extension cohort of ASCC tumors.

scholarly journals Pooled analysis of 115 patients from updated data of Epitopes-HPV01 and Epitopes-HPV02 studies in first-line advanced anal squamous cell carcinoma

2020 ◽  
Vol 12 ◽  
pp. 175883592097535 ◽  
Author(s):  
Stefano Kim ◽  
Aurélia Meurisse ◽  
Laurie Spehner ◽  
Morgane Stouvenot ◽  
Eric François ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Response Rate ◽  
Objective Response ◽  
Locally Advanced ◽  
Complete Response ◽  
Pooled Analysis ◽  
Term Survival ◽  
Anal Squamous Cell Carcinoma

Aims: The addition of docetaxel to cisplatin and 5-fluorouracil (DCF) has shown promising efficacy in advanced squamous cell carcinoma of the anus (SCCA). Preliminary results of Epitopes-HPV01 study showed a high rate of long-lasting complete response to DCF. The prospective, multicenter, Epitopes-HPV02 trial then confirmed the high efficacy of the modified DCF (mDCF) regimen in terms of complete response rate and long-term survival in metastatic or non-resectable locally advanced recurrent SCCA. Here, we present updated results of the Epitopes-HPV01 and Epitopes-HPV02 studies. Patients & methods: Epitopes-HPV01 is a prospective study performed by the regional cancer network of Franche-Comté, France. Epitopes-HPV02 is a phase II study supported by two French collaborative oncological groups, performed in 25 centers. Both studies included patients with metastatic, or with unresectable local recurrent SCCA, treated with DCF regimen. Results: In Epitopes-HPV01, 51 patients were enrolled between September 2012 and January 2019, and 49 patients were included for analysis; while 69 patients were included between September 2014 and December 2016 in Epitopes-HPV02, and 66 patients for analysis. Pooled analysis of 115 patients showed a median progression-free survival of 12.2 months [95% confidence interval (CI) 10.6–16.1] [11.0 months (9.3–16.0) in -HPV02, and 15.6 months (11.2–34.5) in -HPV01, ( p = 0.06)]. The median overall survival was 39.2 months (26.0–109.1) [36.3 in -HPV02 (25.2–NR), and 61.1 months (21.4–120.0) in -HPV01 ( p = 0.62)]. Objective response rate was 87.7% (90.9% in -HPV02 and 83.3% in -HPV01) with 40.3% of complete response (45.5% in -HPV02 and 33.3% in -HPV01). No differences were observed between standard DCF ( n = 54) and mDCF ( n = 58) in terms of OS ( p = 0.57) and PFS ( p = 0.99). 5-years PFS and OS rates were 24.5% and 44.4%, respectively, in the whole population. No treatment-related death was observed. Conclusion: Updated results of Epitopes-HPV01 and 02 studies, as well as the pooled analysis, confirm mDCF as a standard treatment in patients with advanced SCCA.

Chemoradiation and maintenance chemotherapy with cisplatin and 5-fluorouracil in anal squamous cell carcinoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14057-14057
Author(s):  
J. Ahn ◽  
B. Cho ◽  
H. Choi ◽  
H. Jeung ◽  
S. Rha ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Locally Advanced ◽  
External Beam Radiation ◽  
External Beam ◽  
Maintenance Chemotherapy ◽  
Beam Radiation ◽  
Anal Squamous Cell Carcinoma ◽  
Excellent Outcome

14057 Background: Chemoradiation is the standard treatment for anal carcinoma. Mitomycin-C (MMC) with 5-fluorouracil (5-FU) is the widely used regimen, but MMC is not a radiation sensitizer and has significant toxicities. This study was conducted to update our experience in treating anal carcinomas with an external beam radiation and continuous infusion of 5-FU with cisplatin. Methods: Twenty-eight patients with locally advanced squamous cell carcinoma of the anus were treated between 1995 and 2005. The primary tumor and involved lymph nodes received a total of 41.4–64.8 Gy and 39.6–60.4 Gy, respectively. Chemotherapy consisted of 5-FU (1,000 mg/m2 CI, D1–5 and D36–40) and cisplatin (80 mg/m2 IVF, D2 and D37) q 4weeks for 4 courses. Results: One patients had T1 lesions, 15 had T2, 7 had T3, and 5 patients had T4 disease. Seventeen patients presented with clinically detectable lymphadenopathy. Eight patients failed to start maintenance chemotherapy due to events during chemoradiation. Of the 19 patients who started maintenance chemotherapy, 3 failed to complete all four courses due to intolerance to chemotherapy. With a median follow-up duration of 68.5 months, the actuarial 5-year OS rate was 83.2 %, the DFS rate 80.7%, and the colostomy-free survival was 91.7%. Patterns of recurrence were local relapses in 3 patients, distant metastases in 2, and both in 1, respectively. Seventeen patients (60.7%) developed moist skin reaction, which frequently caused the interruption of radiotherapy. Principal grade 3/4 hematologic toxicities were neutropenia in 10 patients (35.8%) and thrombocytopenia in 4 (14.2%). The most common late complications were lymphedema (14.3%). Conclusions: Our results demonstrate that combined modality therapy with external beam radiation, cisplatin and 5-FU yields an excellent outcome in terms of survival and sphincter preservation which is comparable to the results of MMC regimens. No significant financial relationships to disclose.

The Management and Prevention of Anal Squamous Cell Carcinoma

2019 ◽  
pp. 216-225 ◽  
Author(s):  
Cathy Eng ◽  
Craig Messick ◽  
Rob Glynne-Jones
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Hpv Vaccination ◽  
Locally Advanced ◽  
Standard Of Care ◽  
The United States ◽  
Oncologic Outcomes ◽  
Prior History ◽  
Anal Squamous Cell Carcinoma

Our aim is to discuss the current established management of care and associated prevention strategies of anal squamous cell carcinoma (SCCA). In general, the development of SCCA is commonly linked to a prior history of HPV. Unfortunately, HPV vaccination continues to be underutilized in the United States versus other countries. Increased acknowledgment of the importance of HPV vaccination as an anticancer vaccine should be encouraged. The present standard of care is primary chemoradiotherapy (CRT), which results in a high level of disease control for small, early-stage SCCA. More advanced cancers still fare poorly with this treatment, and the disease relapses locoregionally in the majority of cases (30%–50% of patients), resulting in an abdominoperineal resection. Current treatment recommendations are associated with substantial morbidity; alternative radiation doses and/or novel combinations of agents with CRT are needed to improve quality of life and oncologic outcomes. Cytotoxic chemotherapy remains the standard of care for treatment-naïve patients with metastatic disease, with a possible new treatment paradigm of carboplatin/weekly paclitaxel. In addition, immune checkpoint inhibition appears to have a promising role in the setting of patients with refractory disease. Several clinical trials with immunotherapeutic and vaccine approaches for locally advanced and metastatic anal cancer are ongoing, as are HPV-agnostic umbrella trials. Whenever possible, clinical trial enrollment is always encouraged for further therapeutic development in the setting of a rare cancer, given the potentially substantial global impact for other HPV-associated malignancies.

Volumetric analysis of anal cancer relapses following radical chemoradiation.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 576-576
Author(s):  
Rebecca Muirhead ◽  
Lisa Durrant ◽  
Katherine Hyde ◽  
Maria Hawkins
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Relapse Rate ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Local Relapse ◽  
Planning System ◽  
Radiotherapy Planning ◽  
Anal Squamous Cell Carcinoma ◽  
Ptv Margin

576 Background: Definitive chemoradiotherapy is standard of care in anal squamous cell carcinoma. The ACT II trial set the standard achieving three year overall survival rates of 73%. However patients with locally advanced disease have a ~50% local relapse rate. Studies have failed to demonstrate an improvement in local relapse rate by altering the systemic therapy. Although 2/3 of relapses are local as opposed to regional or distant, there is limited knowledge on the 3D position of these relapses. We aim to retrospectively review the patterns of local failure in three dimensions, relative to the radiotherapy plan. Methods: Between February 2007 and April 2012, 77 patients were treated for squamous cell carcinoma of the anus with radical chemoradiotherapy. Early stage (T0/2) and locally advanced (T3/4) tumours constituted 53% and 44% respectively. 37% of patients had nodal disease. As per ACT II protocol we used a gross tumour volume (GTV) to PTV margin of 3cm and prescribed to a dose of 50.4Gy. In patients with a local recurrence, imaging from the time of recurrence was imported into the radiotherapy planning system. The volume and site of gross recurrence was noted relative to the previous GTV and 95% isodose line. The mean dose delivered to the relapsed area was calculated. Results: Median follow-up was 42 months (range 14 to 78 months). Eight (10%) patients failed to respond. Six (8%) patients developed an isolated local relapse, 2 (3%) distant metastatic disease alone and 1 both local and distant relapse. Of those that relapsed locally, 5 patients were T2N0, one T3N0 and 1 node positive. There were no regional relapses. The entire macroscopic relapse lay within the 95% isodose line of the 50.4Gy in all patients. The median percentage of relapse that lay within GTV was 63% (range 29 to 100%). A GTV to PTV margin of 2cm would have encompassed all macroscopic relapses. The median doses to relapsed area was 52Gy (range 51Gy to 53Gy) with the minimum dose to any relapsed area being 49Gy. Conclusions: The majority of relapses centred on the GTV suggesting the gross tumour was uncontrolled with current doses in these patients. A reduction of GTV to PTV margin may be appropriate, facilitating trials of dose escalation with the aim of improving outcomes.

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