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Cancers
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Research on Anal Squamous Cell Carcinoma
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Research on Anal Squamous Cell Carcinoma

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (1 July 2021) | Viewed by 19386

Special Issue Editors

Dr. Christopher L. Hallemeier

E-Mail Website
Guest Editor
Department of Radiation Oncology, Mayo Clinic, Rochester, MN 55905, USA
Interests: esophageal cancer; proton radiotherapy; SBRT
Special Issues, Collections and Topics in MDPI journals
Dr. Krishan R. Jethwa

E-Mail Website
Guest Editor
Department of Therapeutic Radiology, Yale University School of Medicine, 15 York Street, PO Box 208040, New Haven, CT 06520-80, USA
Interests: gastrointestinal cancer; radiotherapy; proton therapy; precision medicine; comparative effectiveness
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Anal canal and peri-anal squamous cell carcinomas (ASCC) are relatively rare cancers which affect approximately 8000 patients per year in the United States. The rate appears to be rising, which is potentially attributable to the increasing incidence of oncogenic human papilloma virus (HPV) infection. Historically, patients were treated with abdominoperineal resection with resulting permanent colostomy dependence. Through landmark efforts and sequentially designed clinical trials, the majority of patients with localized disease are now effectively treated with radiotherapy and chemotherapy, or in select cases, sphincter-preserving surgery, with favorable outcomes. However, continued efforts are needed to gain a better understanding of ASCC disease biology and to continue improving cancer control while maximizing the quality of life for patients. The purpose of this Special Issue is to discuss the historical perspectives of surgery, radiotherapy, and systemic therapy, the evolution of therapy over time, and current areas of investigation to advance our understanding of the multidisciplinary management of patients with ASCC.

Dr. Christopher L. Hallemeier
Dr. Krishan R. Jethwa
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • anal canal
  • peri-anal
  • squamous cell carcinoma
  • surgery
  • radiotherapy
  • chemotherapy

Published Papers (7 papers)

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Editorial

Jump to: Research, Review

2 pages, 157 KiB  
Editorial
Research on Anal Squamous Cell Carcinoma
by Krishan R. Jethwa and Christopher L. Hallemeier
Cancers 2022, 14(1), 42; https://doi.org/10.3390/cancers14010042 - 23 Dec 2021
Viewed by 1715
Abstract
Anal canal and peri-anal squamous cell carcinomas (ASCCs) are relatively rare cancers that affect approximately 8000 patients per year in the United States [...] Full article
(This article belongs to the Special Issue Research on Anal Squamous Cell Carcinoma)

Research

Jump to: Editorial, Review

11 pages, 811 KiB  
Article
Intensified Induction Chemotherapy in Locally Advanced Squamous Cell Carcinoma of the Anus—A Population-Based Experience from the Danish Anal Cancer Group
by Karen Lycke Wind, Lisbeth Riber, Birgitte Mayland Havelund, Eva Serup-Hansen, Camilla Kronborg, Mette Marie Fode, Anders Jakobsen and Karen-Lise Garm Spindler
Cancers 2021, 13(13), 3226; https://doi.org/10.3390/cancers13133226 - 28 Jun 2021
Cited by 3 | Viewed by 1597
Abstract
Locally advanced squamous cell carcinoma of the anus (LASCCA) has a poor prognosis with a high risk of treatment failure calling for intensified therapy. We present the long-term follow-up of a nationwide cohort of LASCCA treated with intensified induction chemotherapy (ICT). The study [...] Read more.
Locally advanced squamous cell carcinoma of the anus (LASCCA) has a poor prognosis with a high risk of treatment failure calling for intensified therapy. We present the long-term follow-up of a nationwide cohort of LASCCA treated with intensified induction chemotherapy (ICT). The study included patients with LASCCA (T3-4N0 or T1-4N+) treated with at least one cycle of ICT (cisplatin, ifosfamide, leucoverin, and 5-flourouracil) between 1998–2018. Data were retrospectively collected from medical records, and statistics were performed in STATA 16.1. In total, 166 patients with LASCCA were identified. Following ICT, 157 patients (95%) received primary curative treatment with either radiotherapy (70%), chemoradiotherapy (27%), or abdominal perineal resection (3%). The overall local tumor response rate after ICT was 76% with 20 (13%) achieving complete local tumor response. After the primary treatment, 123 patients (79%) obtained complete response, and 27 underwent salvage surgery due to persistent disease. The median follow-up time was 6 years, local and distant failure rates 22% and 13%, respectively. The 3- and 5-year disease-free survival rates were 70% and 67%, and the 3- and 5-year overall survival rates were 76% and 70%, respectively. Intensified ICT regimen could be a supplementary treatment option in the most advanced cases of LASCCA. Prospective randomized trials are needed to investigate this approach further. Full article
(This article belongs to the Special Issue Research on Anal Squamous Cell Carcinoma)
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13 pages, 770 KiB  
Article
Volumetric Modulated Arc Therapy Improves Outcomes in Definitive Radiochemotherapy for Anal Cancer Whilst Reducing Acute Toxicities and Increasing Treatment Compliance
by Jacqueline Possiel, Hanne Elisabeth Ammon, Manuel Guhlich, Lena-Christin Conradi, Michael Ghadimi, Hendrik Andreas Wolff, Markus Anton Schirmer, Stephan Samel, Michael Mügge, Stefan Rieken, Martin Leu and Leif Hendrik Dröge
Cancers 2021, 13(11), 2533; https://doi.org/10.3390/cancers13112533 - 21 May 2021
Cited by 4 | Viewed by 1828
Abstract
Background: Intensity-modulated radiotherapy (IMRT) is the standard of care in chemoradiotherapy (CRT) for anal cancer. Until now, only a limited number of studies have analyzed the results with VMAT (volumetric modulated arc therapy). We conducted a retrospective study on patients treated at our [...] Read more.
Background: Intensity-modulated radiotherapy (IMRT) is the standard of care in chemoradiotherapy (CRT) for anal cancer. Until now, only a limited number of studies have analyzed the results with VMAT (volumetric modulated arc therapy). We conducted a retrospective study on patients treated at our institution. Patients and Methods: We included patients who received curative CRT for anal cancer. We compared VMAT-treated and 3DCRT (3D conformal radiotherapy)-treated patients. We analyzed toxicities (acute: CTCAE criteria; late: LENT/SOMA criteria), treatment compliance, overall survival, cancer-specific survival (CSS), distant control (DC), and locoregional control. Results: A total of 149 patients (3DCRT: n = 87, VMAT: n = 62) were included. The median follow-up was longer in 3DCRT-treated patients (3DCRT: 61.3 months; VMAT: 39.1 months; p < 0.05). VMAT-treated patients had more G3 tumors (3DCRT: 12/87 (13.8%); VMAT: 18/62 (29.0%), p < 0.001). VMAT reduced acute toxicities ≥grade 3 (3DCRT: n = 48/87 (55.2%); VMAT: n = 11/62 (17.7%), p < 0.001). VMAT improved treatment compliance (less interruptions/delays) (3DCRT: 37/87, 42.5%; VMAT: 4/62, 6.5%; p < 0.001), provided a shorter median overall treatment time (3DCRT: 41 days; VMAT: 38 days; p = 0.02), and gave a higher median absolute 5-fluorouracil dose (3DCRT: 13,700 mg; VMAT: 14,400 mg; p = 0.001). Finally, we found improved CSS (p = 0.02; 3DCRT: 81.9% at 3 years; VMAT: 94.1% at 3 years) and DC (p = 0.01; 3DCRT: 89.4% at 3 years; VMAT: 100.0% at 3 years) with VMAT. Summary: Our study is the first to demonstrate improved treatment compliance and outcomes with VMAT for anal cancer. Previous studies have indicated that organs at risk sparing might be more improved with the use of VMAT vs. with conventional IMRT. Future studies should address whether these advantages lead to a further reduction in CRT-associated morbidity. Full article
(This article belongs to the Special Issue Research on Anal Squamous Cell Carcinoma)
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11 pages, 7469 KiB  
Article
The Clinical Value of Measuring Circulating HPV DNA during Chemo-Radiotherapy in Squamous Cell Carcinoma of the Anus
by Anna C. Lefèvre, Niels Pallisgaard, Camilla Kronborg, Karen L. Wind, Søren R. P. Krag and Karen-Lise G. Spindler
Cancers 2021, 13(10), 2451; https://doi.org/10.3390/cancers13102451 - 18 May 2021
Cited by 24 | Viewed by 2249
Abstract
Background and purpose: Circulating tumor DNA (ctDNA) is investigated in various cancers. In squamous cell carcinoma of the anus (SCCA) infection with human papilloma virus (HPV) is found in around 90% of cases and here, plasma HPV (pHPV) can be used as ctDNA. [...] Read more.
Background and purpose: Circulating tumor DNA (ctDNA) is investigated in various cancers. In squamous cell carcinoma of the anus (SCCA) infection with human papilloma virus (HPV) is found in around 90% of cases and here, plasma HPV (pHPV) can be used as ctDNA. Preliminary data have proved the ability to detect pHPV16 and -18 in SCCA. We have developed a highly sensitive method for measurement of six relevant pHPV subtypes, to investigate the elimination pattern of pHPV during chemo-radiotherapy (CRT) for SCCA and its clinical value. Material and methods: Patients treated at Aarhus University Hospital from 2016–2020 were included. P16 status in the primary biopsy was measured and 82% of patients had P16 positive tumor. Blood samples were collected prior to treatment (PT), mid treatment (MT), end of therapy (EOT), and during follow-up (FU). An in-house multiplex digital droplet PCR method measured pHPV subtypes 16, 18, 31, 33, 51, 58. Results: Samples from 88 patients were drawn PT (n = 73), MT (n = 72), EOT (n = 64) and during FU (n = 41). Plasma HPV was detectable in 52 patients and PT pHPV levels correlated to tumor stages. Three elimination patterns were observed during CRT with correlation to outcome: fast responders with no local or distant failures (0/12); slow responders with high risk of local failures (4/20), no distant failures; persistent molecular responders with high risk of distant failures (4/13), but no local failures, p < 0.01. Conclusion: During CRT, pHPV can divide patients with SCCA into three groups with significantly different risk of failure. The use of pHPV can potentially assist in clinical treatment decision. Full article
(This article belongs to the Special Issue Research on Anal Squamous Cell Carcinoma)
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Review

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13 pages, 653 KiB  
Review
Present and Future Research on Anal Squamous Cell Carcinoma
by Laurie Spehner, Jihane Boustani, Luc Cabel, Jérôme Doyen, Angélique Vienot, Christophe Borg and Stefano Kim
Cancers 2021, 13(15), 3895; https://doi.org/10.3390/cancers13153895 - 02 Aug 2021
Cited by 11 | Viewed by 2443
Abstract
Squamous cell carcinoma of the anus is an orphan disease, and after more than three decades of no substantial advances in disease knowledge and treatment, it is finally gaining momentum with the arrival of a taxane-based chemotherapy and immunotherapy. Currently, about 20 combination [...] Read more.
Squamous cell carcinoma of the anus is an orphan disease, and after more than three decades of no substantial advances in disease knowledge and treatment, it is finally gaining momentum with the arrival of a taxane-based chemotherapy and immunotherapy. Currently, about 20 combination clinical trials with an anti-PD1/L1 are ongoing in localized and advanced stages, in association with radiotherapy, chemotherapy, tumor vaccines, anti-CTLA4, anti-EGFR, or antiangiogenic molecules. Moreover, a new biomarker with high sensitivity and specificity such as HPV circulating tumor DNA (HPV ctDNA) by liquid biopsy, is improving not only the prognostic measurement but also the treatment strategy guidance for this disease. Finally, better understanding of potential targets is reshaping the present and future clinical research in this unique, HPV genotype-16-related disease in the great majority of patients. Full article
(This article belongs to the Special Issue Research on Anal Squamous Cell Carcinoma)
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16 pages, 1371 KiB  
Review
Research on Anal Squamous Cell Carcinoma: Systemic Therapy Strategies for Anal Cancer
by Ryan M. Carr, Zhaohui Jin and Joleen Hubbard
Cancers 2021, 13(9), 2180; https://doi.org/10.3390/cancers13092180 - 01 May 2021
Cited by 9 | Viewed by 3831
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Research on Anal Squamous Cell Carcinoma)
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24 pages, 1578 KiB  
Review
Evolution of the Role of Radiotherapy for Anal Cancer
by Edward Christopher Dee, James D. Byrne and Jennifer Y. Wo
Cancers 2021, 13(6), 1208; https://doi.org/10.3390/cancers13061208 - 10 Mar 2021
Cited by 12 | Viewed by 4740
Abstract
Prior to the 1980s, the primary management of localized anal cancer was surgical resection. Dr. Norman Nigro and colleagues introduced neoadjuvant chemoradiotherapy prior to abdominoperineal resection. Chemoradiotherapy 5-fluorouracil and mitomycin C afforded patients complete pathologic response and obviated the need for upfront surgery. [...] Read more.
Prior to the 1980s, the primary management of localized anal cancer was surgical resection. Dr. Norman Nigro and colleagues introduced neoadjuvant chemoradiotherapy prior to abdominoperineal resection. Chemoradiotherapy 5-fluorouracil and mitomycin C afforded patients complete pathologic response and obviated the need for upfront surgery. More recent studies have attempted to alter or exclude chemotherapy used in the Nigro regimen to mitigate toxicity, often with worse outcomes. Reductions in acute adverse effects have been associated with marked advancements in radiotherapy delivery using intensity-modulated radiation therapy (IMRT) and image-guidance radiation delivery, resulting in increased tolerance to greater radiation doses. Ongoing trials are attempting to improve IMRT-based treatment of locally advanced disease with efforts to increase personalized treatment. Studies are also examining the role of newer treatment modalities such as proton therapy in treating anal cancer. Here we review the evolution of radiotherapy for anal cancer and describe recent advances. We also elaborate on radiotherapy’s role in locally persistent or recurrent anal cancer. Full article
(This article belongs to the Special Issue Research on Anal Squamous Cell Carcinoma)
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