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.

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.

scholarly journals Induction Chemotherapy in Head and Neck Squamous Cell Carcinoma: A Question of Belief

Cancers ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 15 ◽  
Author(s):  
Andy Karabajakian ◽  
Max Gau ◽  
Thibault Reverdy ◽  
Eve-Marie Neidhardt ◽  
Jérôme Fayette
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Induction Chemotherapy ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Neck Squamous Cell Carcinoma ◽  
Larynx Preservation ◽  
Distant Failure

Induction chemotherapy (IC) in locally advanced head and neck squamous cell carcinoma (LA HNSCC) has been used for decades. However, its role is yet to be clearly defined outside of larynx preservation. Patients with high risk of distant failure might potentially benefit from sequential treatment. It is now widely accepted that TPF (docetaxel, cisplatin, and fluorouracil) is the standard IC regimen. Essays that have compared this approach with the standard of care, concurrent chemoradiotherapy (CCRT), are mostly inconclusive. Radiotherapy (RT) can be used in the post-IC setting and be sensitized by chemotherapy or cetuximab. Again, no consensus exists but there seems to be trend in favor of potentiation by cisplatin. Less toxic schemes of IC are tested as toxicity is a major issue with TPF. IC might have an interesting role in human papilloma virus (HPV)-related LA HNSCC and lead to CCRT de-escalation.

scholarly journals Investigating epidemiologic trends and the geographic distribution of patients with anal squamous cell carcinoma throughout Canada

2020 ◽  
Vol 27 (3) ◽  
Author(s):  
L. Cattelan ◽  
F. M. Ghazawi ◽  
M. Le ◽  
E. Savin ◽  
A. Zubarev ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Anal Cancer ◽  
Squamous Cell ◽  
Demographic Data ◽  
Cancer Registries ◽  
The United States ◽  
Incidence Rates ◽  
Anal Squamous Cell Carcinoma ◽  
Incidence And Mortality

Background Anal cancer is a rare disease, constituting 0.5% of new cancer cases in the United States. The most common subtype is squamous cell carcinoma (scc). Studies in several developed nations have reported on an increasing incidence of anal cancer in recent decades, and various risk factors pertaining to the pathogenesis of the disease have been identified, including infection with the human papillomavirus, tobacco use, and immunosuppression. The epidemiology and distribution of anal scc throughout Canada remain poorly understood, however. Methods Using 3 population-based cancer registries, a retrospective analysis of demographic data across Canada for 1992–2010 was performed. The incidence and mortality for anal scc was examined at the levels of provinces, cities, and the forward  sortation area (FSA) component (first 3 characters) of postal codes. Results During 1992–2010, 3720 individuals were diagnosed with anal scc in Canada; 64% were women. The overall national incidence rate was 6.3 cases per million population per year, with an average age at diagnosis of 60.4 years. The incidence increased over time, with significantly higher incidence rates documented in British Columbia and Nova Scotia (9.3 cases per million population each). Closer examination revealed clustering of cases in various urban centres and self-identified lgbtq communities in Toronto, Montreal, and Vancouver. Discussion This study provides, for the first time, a comprehensive analysis of the burden of anal scc in Canada, identifying susceptible populations and shedding light onto novel avenues of research to lower the incidence of anal cancer throughout the country.

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 EGFR Monoclonal Antibodies in the Treatment of Squamous Cell Carcinoma of the Head and Neck: A View beyond Cetuximab

2012 ◽  
Vol 2012 ◽  
pp. 1-10
Author(s):  
Scott A. Kono ◽  
Missak Haigentz ◽  
Sue S. Yom ◽  
Nabil Saba
Keyword(s):  
Squamous Cell Carcinoma ◽  
Monoclonal Antibodies ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Metastatic Disease ◽  
Squamous Cell ◽  
Locally Advanced ◽  
The United States ◽  
Primary Therapy ◽  
Metastatic Setting

Squamous cell carcinoma of the head and neck (SCCHN) is a prevalent disease both in the United States and worldwide with an overall poor prognosis, in part due to limited activity of existing therapy. Primary therapy is largely dictated by the anatomical origin of the cancer and whether distant disease is present. Many patients with localized disease are treated with chemoradiotherapy, either in the definitive or adjuvant setting, and those with metastatic disease are treated with palliative chemotherapy. The chemotherapy used in SCCHN can be toxic, whether given with radiation or alone. The epidermal growth factor receptor (EGFR) is highly expressed in SCCHN and serves as a logical therapeutic target. EGFR-directed monoclonal antibodies (MoAbs) have higher activity in SCCHN than small molecule tyrosine kinase inhibitors. Cetuximab, a widely studied EGFR MoAb, is FDA approved in the metastatic setting, as well as with radiation for locally advanced disease. Despite improvements in survival when cetuximab is incorporated with chemotherapy for metastatic disease, the prognosis of patients remains poor. Novel EGFR MoAbs are being developed with the goal of improving efficacy and tolerability. This paper will summarize the use of EGFR-directed MoAbs in treating SCCHN with a focus on novel agents being tested.

scholarly journals Phase I Trial of Dose-Escalated Stereotactic Radiosurgery (SRS) Boost for Unfavorable Locally Advanced Oropharyngeal Cancer

2020 ◽  
Author(s):  
Prashant Vempati ◽  
Aditya N. Halthore ◽  
Sewit Teckie ◽  
Zaker Rana ◽  
Emile Gogineni ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Phase I ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Dose Escalation ◽  
Phase I Trial ◽  
Locally Advanced ◽  
Oncologic Outcomes ◽  
Oropharynx Squamous Cell Carcinoma

Abstract Background and Purpose: Patients with locally advanced oropharynx squamous cell carcinoma have suboptimal outcomes with standard chemoradiation. Here, we evaluated toxicity and oncologic outcomes of dose escalation using radiosurgical boost for patients with unfavorable oropharynx squamous cell carcinoma. Materials and Methods: Between 2010-2017, Thirty four patients with intermediate- or high-risk oropharynx squamous cell carcinoma were enrolled onto this prospective phase I trial. Each patient received concurrent cisplatin and fractionated radiotherapy totaling 60 Gy or 66 Gy followed by radiosurgery boost to areas of residual gross tumor: single fraction of 8 Gy or 10 Gy, or two fractions of 5 Gy each. Primary endpoint was treatment toxicity. Secondary endpoints were local, regional, and distant disease control.Results: Eleven, sixteen and seven patients received radiosurgery boost with 8 Gy in 1 fraction, 10 Gy in 1 fraction, and 10 Gy in 2 fractions respectively. Acute toxicities include 4 patients with tumor necrosis causing grade 3 dysphagia, of which 3 developed grade 4 pharyngeal hemorrhage requiring surgical intervention. At 24 months after treatment, 7%, 9%, and 15% had grade 2 dysgeusia, xerostomia, and dysphagia, respectively, and two patients remained feeding tube dependent. No grade 5 toxicities occurred secondary to treatment. Local, regional, and distant control at a median follow up of 4.2 years were 85.3%, 85.3% and 88.2%, respectively. Five patients died resulting in overall survival of 85.3%. Conclusions: This study is the first to report the use of radiosurgery boost dose escalation in patients with unfavorable oropharynx squamous cell carcinoma. Longer follow-up, larger cohorts, and further refinement of boost methodology are needed prior to implementation in routine clinical practice.Trial Registration: Northwell Health Protocol #09-309A (NCT02703493) (https://clinicaltrials.gov/ct2/show/NCT02703493)

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.

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