Research on Anal Squamous Cell Carcinoma: Systemic Therapy Strategies for Anal Cancer

Anal squamous cell carcinoma (ASCC) is a rare malignancy, with most cases associated with human papilloma virus and an increased incidence in immunocompromised patients. Progress in management of ASCC has been limited not only due to its rarity, but also the associated lack of research funding and social stigma. Historically, standard of care for invasive ASCC has been highly morbid surgical resection, requiring a permanent colostomy. Surgery was associated with disease recurrence in approximately half of the patients. However, the use of chemotherapy (5-fluorouracil and mitomycin C) concomitantly with radiation in the 1970s resulted in disease regression, curing a subset of patients and sparing them from morbid surgery. Validation of the use of systemic therapy in prospective trials was not achieved until approximately 20 years later. In this review, advancements and shortcomings in the use of systemic therapy in the management of ASCC will be discussed. Not only will standard-of-care systemic therapies for locoregional and metastatic disease be reviewed, but the evolving role of novel treatment strategies such as immune checkpoint inhibitors, HPV-based vaccines, and molecularly targeted therapies will also be covered. While advances in ASCC treatment have remained largely incremental, with increased biological insight, an increasing number of promising systemic treatment modalities are being explored.

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How I treat anal squamous cell carcinoma

ESMO Open ◽

10.1136/esmoopen-2020-000711 ◽

2020 ◽

Vol 4 (Suppl 2) ◽

pp. e000711

Author(s):

Giulia Martini ◽

Gianluca Arrichiello ◽

Carola Borrelli ◽

Luca Poliero ◽

Erika Martinelli

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

De Novo ◽

Checkpoint Inhibitors ◽

Early Stage ◽

Single Agent ◽

Hpv Infection ◽

Anal Squamous Cell Carcinoma ◽

Systemic Treatments

Squamous cell carcinoma of the anus (SCCA) is a rising health issue, strongly related to other relevant medical conditions such as (HIV) and human papillomavirus (HPV) infection. Correct assessment of patients with SCCA requires a multidisciplinary evaluation and adequate follow-up. Accurate local and systemic staging, as well as risk evaluation, are essential to optimal treatment planning. Early stage tumours can be definitively treated with a combination of chemotherapy and radiotherapy, while salvage surgery is usually reserved for patients who develop local recurrence. Distant recurrence and de novo metastatic disease are associated with poorer prognosis and require palliative systemic chemotherapy, with different single agent and combination options available. Finally, recent discoveries on the carcinogenesis of SCCA have allowed the development of innovative treatment options, the most promising being immune checkpoint inhibitors. The limited systemic treatments for SCCA and low incidence of the disease, together with insufficient data from clinical research could explain the poor outcomes of these patients, which should therefore be managed in high volume centres and enrolled in clinical trials whenever possible. This article summarises the main strategies for treating patients with SCCA.

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RATIONALE 311: tislelizumab plus concurrent chemoradiotherapy for localized esophageal squamous cell carcinoma

Future Oncology ◽

10.2217/fon-2021-0632 ◽

2021 ◽

Author(s):

Rong Yu ◽

Wenqing Wang ◽

Tao Li ◽

Jiancheng Li ◽

Kuaile Zhao ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Concurrent Chemoradiotherapy ◽

Checkpoint Inhibitors ◽

Standard Of Care ◽

Phase Iii ◽

Double Blind ◽

Cell Clearance

Definitive chemoradiotherapy is the standard of care for inoperable locoregionally advanced esophageal squamous cell carcinoma (ESCC). Immune checkpoint inhibitors such as anti-PD-1/PD-L1 antibodies have led to a paradigm shift in advanced, metastatic ESCC treatment; however, the effect of incorporating checkpoint inhibitors in the definitive management of ESCC is unclear. Tislelizumab is an anti-PD-1 antibody specifically engineered to minimize FcɣR binding on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. The RATIONALE 311 study described here (BGB-A317-311; NCT03957590) is a registrational multicenter, double-blind, placebo-controlled, randomized, Phase III clinical trial designed to evaluate the efficacy and safety of tislelizumab combined with concurrent chemoradiotherapy in patients with inoperable localized ESCC.

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The Management and Prevention of Anal Squamous Cell Carcinoma

American Society of Clinical Oncology Educational Book ◽

10.1200/edbk_237433 ◽

2019 ◽

pp. 216-225 ◽

Cited By ~ 3

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.

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EP.FRI.253 Outcomes of treatment of anal squamous cell carcinoma over a 10-year period

British Journal of Surgery ◽

10.1093/bjs/znab312.046 ◽

2021 ◽

Vol 108 (Supplement_7) ◽

Author(s):

Abraham Ayantunde ◽

Khaled Noureldin ◽

Daniel Edison ◽

Hafizul Haq ◽

Bandipalyam Praveen

Keyword(s):

Squamous Cell Carcinoma ◽

Survival Rate ◽

Cell Carcinoma ◽

Squamous Cell ◽

Carcinoid Tumour ◽

Palliative Therapy ◽

Treatment Modalities ◽

Curative Intent ◽

Anal Squamous Cell Carcinoma ◽

Female Ratio

Abstract Background We evaluated our 10-year experience with the treatment and outcomes of patients with anal squamous cell carcinoma (ASCC). Patients and Method Clinical and pathological data of patients with ASCC were analysed between January 2011 and December 2019. All patients underwent the standard workup according to the anal cancer network guidelines and treated accordingly. Patients were followed up clinically and with imaging according to the network protocol. The outcome measures were clinicopathological characteristics, treatment modalities, recurrent disease, disease-free and overall survival. Results 117 patients were diagnosed with ASCC over the 10-year period. 14 patients with adenocarcinoma(11), melanoma(1), Paget disease(1) and carcinoid tumour(1) were excluded. Median age of 103 patients included was 68 (38-101) years with a Male to female ratio of 1:2. Four patients were HIV positive and 42.7% of the patients had AIN of varying degree of dysplasia. 66% (68/103) of the patients had radical chemoradiotherapy with curative intent while 9 patients with tumour ≤2cm underwent wide local excision. Six patients underwent palliative therapy and the remaining 20 were on supportive palliative care. 61.2% of the patients treated with radical chemoradiotherapy had complete response while 10.7% had partial response. Four patients with incomplete response underwent salvage APER. 13% (10/77) of the patients treated with curative intention developed recurrence. The overall mean survival time was 77.9 (95% CI 66.73-89.06) months with 5-year survival rate of 59%. The overall mortality rate was 42.7% and disease-specific mortality was 26.2%. Conclusion ASCC responds well to radical chemoradiotherapy with enhanced survival rate.

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Comprehensive characterization of the mutational landscape in localized anal squamous cell carcinoma

10.1101/796367 ◽

2019 ◽

Author(s):

Lucía Trilla-Fuertes ◽

Ismael Ghanem ◽

Joan Maurel ◽

Laura G-Pastrián ◽

Marta Mendiola ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Genetic Variants ◽

Disease Free Survival ◽

Standard Of Care ◽

High Impact ◽

Clinical Samples ◽

Anal Squamous Cell Carcinoma

AbstractPurposeAnal squamous cell carcinoma (ASCC) is a rare neoplasm. Chemo-radiotherapy is the standard of care, with no therapeutic advances achieved over the past three decades. Thus, a deeper molecular characterization of this disease is still necessary.MethodsWe analyzed 46 paraffin-embedded tumor samples from patients diagnosed with primary ASCC by exome sequencing. A bioinformatics approach focused in the identification of high impact genetic variants, which may act as drivers of oncogenesis, was performed. The relation between genetics variant and prognosis was also studied.ResultsThe list of high impact genetic variants was unique for each patient. However, the pathways in which these genes are involved are well-known hallmarks of cancer, such as angiogenesis or immune pathways. Additionally, we determined that genetic variants in BRCA2, ZNF750, FAM208B, ZNF599 and ZC3H13 genes are related with poor disease-free survival in ASCC.ConclusionHigh impact genetic variants in ASCC affect pathways involved in cancer development, and may play a role in the etiology of the disease. Variants in BRCA2, ZNF750, FAM208B, ZNF599 and ZC3H13 genes seem to be related with prognosis in ASCC. Sequencing of ASCC clinical samples appears an encouraging tool for the molecular portrait of this disease.

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Metastatic Squamous Cell Carcinoma of the Anus: Time for a Shift in the Treatment Paradigm?

ISRN Oncology ◽

10.5402/2012/756591 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 4

Author(s):

Alice Dewdney ◽

Sheela Rao

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Metastatic Disease ◽

Squamous Cell ◽

Survival Rates ◽

Treatment Strategies ◽

Phase Ii Trials ◽

Anal Squamous Cell Carcinoma ◽

Rare Tumours ◽

Treatment Paradigm

Anal cancers are rare tumours; however, the incidence is increasing in both men and women. Changing trends in sexual behaviour, smoking, and infection with the human papillomavirus are thought to be responsible for the increase. Patients with metastatic disease have a poor prognosis, with 5-year median overall survival rates of 10% in men and 20% in women. The standard systemic treatment of metastatic disease remains cisplatin and 5-fluorouracil, and aside from several non-randomised small phase II trials there has been no real progress over the past two decades. Based on the efficacy of cetuximab in squamous cell carcinomas from other primary sites, there appears to be clinical rationale for evaluation of anti-epidermal growth factor inhibitors in anal squamous cell carcinoma. In order to facilitate research and implement more effective treatment strategies international collaboration in clinical trials incorporating tissue collection for biomarkers is essential.

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Eating Green: Shining Light on the Use of Dietary Phytochemicals as a Modern Approach in the Prevention and Treatment of Head and Neck Cancers

Current Topics in Medicinal Chemistry ◽

10.2174/1568026618666180112160713 ◽

2018 ◽

Vol 18 (3) ◽

pp. 182-191 ◽

Cited By ~ 10

Author(s):

Linda L. Eastham ◽

Candace M. Howard ◽

Premalatha Balachandran ◽

David S. Pasco ◽

Pier Paolo Claudio

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Cancer Cell ◽

Squamous Cell ◽

Treatment Strategies ◽

Lifestyle Changes ◽

Neck Squamous Cell Carcinoma ◽

Laboratory Research ◽

Modern Approach

Enthusiasm for the use of dietary bioactive compounds as chemopreventive agents and adjuvants for current therapies has increased laboratory research conducted on several types of cancers including Head and Neck Squamous Cell Carcinoma (HNSCC). The green chemoprevention movement is a modern approach to highlight healthy lifestyle changes that aim to decrease the incidence of HNSCC. A healthy diet can be an effective way to prevent the development of oral cancers. Discovery of the naturally occurring plant based compounds called phytochemicals has facilitated the development of new treatment strategies for patients that are at risk for, or have developed HNSCC. Many of these compounds have been shown to elicit very potent anti-carcinogenic properties. While there are many compounds that have been studied, the compounds from two specific categories of phytochemicals, phenolics (resveratrol, EGCG, curcumin, quercetin, and honokiol) and glucosinolates (sulforaphane, PEITC and BITC), are emerging as potent and effective inhibitors of oral carcinogenesis. These compounds have been shown to inhibit HNSCC growth through a variety of mechanisms. Research has demonstrated that these compounds can regulate cancer cell proliferation through the regulation of multiple cell signaling pathways. They can impede cell cycle progression, induce differentiation and apoptosis, prevent angiogenesis, and inhibit cancer cell invasive and metastatic properties. They can protect normal cells during treatment and reduce the damage caused by chemotherapy and radiotherapy. This review aims to provide an overview of some of the most effective phytochemicals that have the potential to successfully prevent and treat head and neck squamous cell carcinoma.

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