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Saralegui Ansorena Y, Enriquez-Navascues JM, Placer Galan C, Borda Arrizabalaga N, Elosegui Aguirrezabala JL, Elorza Echaniz G, Etxart Lopetegi A, Aguirre Allende I. Characteristics and oncological results of epidermoid anal carcinoma: Comparison analysis between immunocompetent and immunosuppressed patients. Cir Esp 2022; 100:709-717. [PMID: 35850478 DOI: 10.1016/j.cireng.2022.07.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Accepted: 05/22/2021] [Indexed: 06/15/2023]
Abstract
OBJECTIVE Most evidence, including recent randomized controlled trials, analysing anal squamous cell carcinoma (SCC) do not consider immunocompromise patient population. The aim of this study was to compare clinical and oncological outcomes among immunocompetent and immunocompromised patients with anal squamous cell carcinoma. METHOD Multicentric retrospective comparative study including 2 cohorts of consecutive patients, immunocompetent and immunocompromised, diagnosed with anal SCC. This study evaluated clinical characteristics, clinical response to radical chemoradiotherapy (CRT) and long-term oncological results including both local and distant recurrence, overall survival (OS) and disease-free survival (DFS). RESULTS A total of 84 patients, 47 (55.6%) female, diagnosed with anal SCC from January 2012 to December 2017 were included, 22 (26%) and 62 (74%) patients in immunocompromised and immunocompetent groups respectively. Patients in immunocompromised group were significantly younger (53 vs. 61 years; P = 0.001), with smaller tumoral size (P = 0.044) and reported higher rates of substance abuse including tobacco use (P = 0.034) and parenteral drug consumption (P = 0.001). No differences were found in administered therapies (P = 301) neither in clinical response to chemoradiotherapy (83 vs. 100%). Moreover, similar 5-year OS (60 vs. 64%; P = 0.756) and DFS (65 vs. 68%; P = 0.338) were observed. CONCLUSION The present study shows no significant differences in long-term oncological results among immunocompetent and immunocompromised patients diagnosed with anal SCC, with a similar oncologic treatment. This evidence might be explained due to the close monitoring and adequate therapeutic control of HIV positive patients.
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Affiliation(s)
- Yolanda Saralegui Ansorena
- Unidad de Cirugía Colorrectal, Servicio de Cirugía General y Digestiva, Hospital Universitario Donostia, Donostia, Gipuzkoa, Spain.
| | - Jose Maria Enriquez-Navascues
- Unidad de Cirugía Colorrectal, Servicio de Cirugía General y Digestiva, Hospital Universitario Donostia, Donostia, Gipuzkoa, Spain
| | - Carlos Placer Galan
- Unidad de Cirugía Colorrectal, Servicio de Cirugía General y Digestiva, Hospital Universitario Donostia, Donostia, Gipuzkoa, Spain
| | - Nerea Borda Arrizabalaga
- Unidad de Cirugía Colorrectal, Servicio de Cirugía General y Digestiva, Hospital Universitario Donostia, Donostia, Gipuzkoa, Spain
| | - Jose Luis Elosegui Aguirrezabala
- Unidad de Cirugía Colorrectal, Servicio de Cirugía General y Digestiva, Hospital Universitario Donostia, Donostia, Gipuzkoa, Spain
| | - Garazi Elorza Echaniz
- Unidad de Cirugía Colorrectal, Servicio de Cirugía General y Digestiva, Hospital Universitario Donostia, Donostia, Gipuzkoa, Spain
| | - Ane Etxart Lopetegi
- Unidad de Cirugía Colorrectal, Servicio de Cirugía General y Digestiva, Hospital Universitario Donostia, Donostia, Gipuzkoa, Spain
| | - Ignacio Aguirre Allende
- Unidad de Cirugía Colorrectal, Servicio de Cirugía General y Digestiva, Hospital Universitario Donostia, Donostia, Gipuzkoa, Spain
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Tchelebi LT, Eng C, Messick CA, Hong TS, Ludmir EB, Kachnic LA, Zaorsky NG. Current treatment and future directions in the management of anal cancer. CA Cancer J Clin 2022; 72:183-195. [PMID: 34847242 DOI: 10.3322/caac.21712] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 09/15/2021] [Accepted: 10/18/2021] [Indexed: 12/18/2022] Open
Abstract
Although rare, the rate of squamous cell carcinoma of the anus (SCCA) is rising globally. Most patients present with nonmetastatic disease and are curable with appropriate treatment, which has evolved significantly over the last several decades. Before the 1970s, SCCA was managed with radical surgery, resulting in a permanent colostomy. Researchers found that preoperative treatment with chemotherapy and concurrent radiation could achieve a pathologic complete response. After this observation, definitive therapy shifted from radical surgery to sphincter-preserving chemoradiation. Investigations into the necessity of chemotherapy and the optimal regimen found that chemotherapy with mitomycin-C and 5-fluorouracil is required for cure. Further studies evaluating the addition of induction or maintenance chemotherapy, monoclonal antibody therapy, or higher radiation doses have demonstrated no significant benefit to disease control. Advanced radiation delivery with intensity-modulated radiotherapy techniques is now considered the standard of care because of its prospectively determined, favorable acute toxicity profile compared with 3-dimensional conformal radiation. It is important to note that chemoradiation treatment response may be slow (up to 26 weeks) and should be assessed through serial clinical examinations. Today, surgical management of SCCA is reserved only for the lowest risk, early stage tumors or for recurrent/persistent disease. Current studies are evaluating radiation dose de-escalation in early stage disease and radiation dose escalation and the addition of immune checkpoint inhibitors in locally advanced cancers. In reviewing how and why modern-day treatment of SCCA was established, the objective of this report is to reenforce adherence to current treatment paradigms to assure the best possible outcomes for patients.
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Affiliation(s)
- Leila T Tchelebi
- Department of Radiation Medicine, Zucker School of Medicine, Hempstead, New York
- Department of Radiation Medicine, Northwell Health Cancer Institute, Mount Kisco, New York
| | - Cathy Eng
- Department of Hematology and Oncology, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee
| | - Craig A Messick
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Theodore S Hong
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Ethan B Ludmir
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Lisa A Kachnic
- Department of Radiation Oncology, Columbia University Irving Medical Center, New York, New York
| | - Nicholas G Zaorsky
- Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve School of Medicine, Cleveland, Ohio
- Department of Radiation Oncology, Penn State Cancer Institute, Hershey, Pennsylvania
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3
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Bushara O, Krogh K, Weinberg SE, Finkelman BS, Sun L, Liao J, Yang GY. Human Immunodeficiency Virus Infection Promotes Human Papillomavirus-Mediated Anal Squamous Carcinogenesis: An Immunologic and Pathobiologic Review. Pathobiology 2021; 89:1-12. [PMID: 34535611 DOI: 10.1159/000518758] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Accepted: 07/28/2021] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Anal squamous cell carcinoma (SCC) is a rare gastrointestinal malignancy with rising incidence, both in the United States and internationally. The primary risk factor for anal SCC is human papillomavirus (HPV) infection. However, there is a growing burden of disease in patients with human immunodeficiency virus (HIV) and HPV coinfection, with the incidence of anal SCC significantly increasing in this population. This is particularly true in HIV-infected men. The epidemiologic correlation between HIV-HPV coinfection and anal SCC is established; however, the immunologic mechanisms underlying this relationship are not well understood. SUMMARY HIV-related immunosuppression due to low circulating CD4+ T cells is one component of increased risk, but other mechanisms, such as the effect of HIV on CD8+ T lymphocyte tumor infiltration and the PD-1/PD-L1 axis in antitumor and antiviral response, is emerging as significant contributors. The goal of this article is to review existing research on HIV-HPV coinfected anal SCC and precancerous lesions, propose explanations for the detrimental synergy of HIV and HPV on the pathogenesis and immunologic response to HPV-associated cancers, and discuss implications for future treatments and immunotherapies in HIV-positive patients with HPV-mediated anal SCC. Key Messages: The incidence of anal squamous cell carcinoma is increased in human immunodeficiency virus (HIV)-infected patients, even in patients on highly active antiretroviral therapy. Locoregional HIV infection may enhance human papillomavirus oncogenicity. Chronic inflammation due to HIV infection may contribute to CD8+ T lymphocyte exhaustion by upregulating PD-1 expression, thereby blunting cytotoxic antitumor response.
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Affiliation(s)
- Omar Bushara
- Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Katrina Krogh
- Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Samuel Edward Weinberg
- Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Brian Steven Finkelman
- Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Leyu Sun
- Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Jie Liao
- Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Guang-Yu Yang
- Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
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4
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Saralegui Ansorena Y, Enriquez-Navascues JM, Placer Galan C, Borda Arrizabalaga N, Elosegui Aguirrezabala JL, Elorza Echaniz G, Etxart Lopetegi A, Aguirre Allende I. Characteristics and oncological results of epidermoid anal carcinoma: Comparison analysis between immunocompetent and immunosuppressed patients. Cir Esp 2021; 100:S0009-739X(21)00207-4. [PMID: 34482903 DOI: 10.1016/j.ciresp.2021.05.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 05/15/2021] [Accepted: 05/22/2021] [Indexed: 10/20/2022]
Abstract
OBJECTIVE Most evidence, including recent randomized controlled trials, analysing anal squamous cell carcinoma (SCC) do not consider immunocompromise patient population. The aim of this study was to compare clinical and oncological outcomes among immunocompetent and immunocompromised patients with anal squamous cell carcinoma. METHOD Multicentric retrospective comparative study including 2 cohorts of consecutive patients, immunocompetent and immunocompromised, diagnosed with anal SCC. This study evaluated clinical characteristics, clinical response to radical chemoradiotherapy (CRT) and long-term oncological results including both local and distant recurrence, overall survival (OS) and disease-free survival (DFS). RESULTS A total of 84 patients, 47 (55.6%) female, diagnosed with anal SCC from January 2012 to December 2017 were included, 22 (26%) and 62 (74%) patients in immunocompromised and immunocompetent groups respectively. Patients in immunocompromised group were significantly younger (53 vs. 61 years; P=0.001), with smaller tumoral size (P=0.044) and reported higher rates of substance abuse. including tobacco use (P=0.034) and parenteral drug consumption (P=0.001). No differences were found in administered therapies (P=301) neither in clinical response to chemoradiotherapy (83 vs. 100%). Moreover, similar 5-year OS (60 vs. 64%; P=0.756) and DFS (65 vs. 68%; P=0.338) were observed. CONCLUSION The present study shows no significant differences in long-term oncological results among immunocompetent and immunocompromised patients diagnosed with anal SCC, with a similar oncologic treatment. This evidence might be explained due to the close monitoring and adequate therapeutic control of HIV positive patients.
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Affiliation(s)
- Yolanda Saralegui Ansorena
- Unidad de Cirugía Colorrectal, Servicio de Cirugía General y Digestiva, Hospital Universitario Donostia, Donostia, Gipuzkoa, España.
| | - Jose Maria Enriquez-Navascues
- Unidad de Cirugía Colorrectal, Servicio de Cirugía General y Digestiva, Hospital Universitario Donostia, Donostia, Gipuzkoa, España
| | - Carlos Placer Galan
- Unidad de Cirugía Colorrectal, Servicio de Cirugía General y Digestiva, Hospital Universitario Donostia, Donostia, Gipuzkoa, España
| | - Nerea Borda Arrizabalaga
- Unidad de Cirugía Colorrectal, Servicio de Cirugía General y Digestiva, Hospital Universitario Donostia, Donostia, Gipuzkoa, España
| | - Jose Luis Elosegui Aguirrezabala
- Unidad de Cirugía Colorrectal, Servicio de Cirugía General y Digestiva, Hospital Universitario Donostia, Donostia, Gipuzkoa, España
| | - Garazi Elorza Echaniz
- Unidad de Cirugía Colorrectal, Servicio de Cirugía General y Digestiva, Hospital Universitario Donostia, Donostia, Gipuzkoa, España
| | - Ane Etxart Lopetegi
- Unidad de Cirugía Colorrectal, Servicio de Cirugía General y Digestiva, Hospital Universitario Donostia, Donostia, Gipuzkoa, España
| | - Ignacio Aguirre Allende
- Unidad de Cirugía Colorrectal, Servicio de Cirugía General y Digestiva, Hospital Universitario Donostia, Donostia, Gipuzkoa, España
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Casadiego-Peña C, Torres-Minacapilli M, Najera M, Ferrer P, Chajon E, Marsiglia H. Difference in toxicity between HIV-positive and HIV-negative patients with squamous-cell cancer of the anal canal treated with concomitant radio-chemotherapy. J Gastrointest Oncol 2020; 11:23-35. [PMID: 32175102 DOI: 10.21037/jgo.2020.01.05] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Background The incidence of squamous cell carcinoma of the anal canal has been increasing over the last 30 years. HIV has been found to be a risk factor for the development of this disease; radio-chemotherapy (RTCT) may also be more toxic than in HIV-negative patients. The study aims at assessing whether there are any differences in terms of toxicity between HIV-positive and HIV-negative patients treated with concomitant RTCT. Methods Search in MEDLINE, EMBASE, CENTRAL (via Cochrane Library-Wiley), DARE, LILACS bibliographic databases. Experimental and analytical observational studies with at least two comparative arms were included: squamous-cell (SC) anal-canal cancer (ACC) treated with RTCT in HIV-positive vs. HIV-negative patients. Results Fifteen publications, 14 retrospective studies and 1 systematic review, were found. All radiotherapy (RT) techniques and all chemotherapeutic agents used to manage this disease were included. No differences were found in terms of duration (P=0.67) and dose (P=0.53) of RT, while CT results were contradictory. Acute and hematological toxicities were significantly higher in HIV-positive patients, while gastrointestinal, dermatological and chronic toxicities did not significantly differ between the two groups. Given the high heterogeneity of the studies, no objective comparison could be made between studies that included antiretrovirals and those that did not. Conclusions HIV-positive patients may be at higher risk for acute and hematological toxicity than HIV-negative patients. A precise conclusion cannot be drawn on the use of antiretrovirals, given the high heterogeneity of data.
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Affiliation(s)
- Camila Casadiego-Peña
- International Master in Advanced Radiotherapy, International Atomic Energy Agency (IAEA)-Fundacion Arturo Lopez Perez (FALP)-Los Andes University, Santiago, Chile
| | - Marcelo Torres-Minacapilli
- International Master in Advanced Radiotherapy, International Atomic Energy Agency (IAEA)-Fundacion Arturo Lopez Perez (FALP)-Los Andes University, Santiago, Chile
| | - Manuel Najera
- Instituto Oncologico Fundacion Arturo Lopez Perez (FALP), Santiago, Chile
| | - Pedro Ferrer
- Instituto Oncologico Fundacion Arturo Lopez Perez (FALP), Santiago, Chile
| | | | - Hugo Marsiglia
- International Master in Advanced Radiotherapy, International Atomic Energy Agency (IAEA)-Fundacion Arturo Lopez Perez (FALP)-Los Andes University, Santiago, Chile.,Instituto Oncologico Fundacion Arturo Lopez Perez (FALP), Santiago, Chile
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6
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Bryant AK, Huynh-Le MP, Simpson DR, Gupta S, Sharabi AB, Murphy JD. Association of HIV Status With Outcomes of Anal Squamous Cell Carcinoma in the Era of Highly Active Antiretroviral Therapy. JAMA Oncol 2019; 4:120-122. [PMID: 28975226 DOI: 10.1001/jamaoncol.2017.2844] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Affiliation(s)
- Alex K Bryant
- Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla
| | - Minh-Phuong Huynh-Le
- Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla
| | - Daniel R Simpson
- Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla
| | - Samir Gupta
- Department of Gastroenterology, University of California, San Diego, La Jolla
| | - Andrew B Sharabi
- Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla
| | - James D Murphy
- Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla.,Clinical and Translational Research Institute, University of California, San Diego, La Jolla
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7
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Abstract
The prevalence of anal human papillomavirus (HPV) infection and anal high-grade squamous intraepithelial lesion (HSIL) remain high among HIV-infected individuals on effective antiretroviral therapy (ART). The incidence of HPV-related anal cancers has continued to increase since the introduction of ART. Therefore, ART may confer only limited benefit with respect to reducing the risk of anal HSIL and cancer. Efforts are in progress to define the efficacy of secondary prevention programs for prevention of anal cancer. In the modern ART era, anal cancer recurrence and survival outcomes are similar in HIV-infected and HIV-uninfected patients, but HIV-infected patients may experience more toxicities. This article reviews the current literature on HPV-associated anal cancer in the HIV-infected population, including epidemiology, screening, clinical characteristics, and treatment outcomes.
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Affiliation(s)
- Chia-Ching J Wang
- Division of Hematology/Oncology, Department of Medicine, Zuckerberg San Francisco General Hospital, San Francisco, CA, USA
- , 995 Potrero Avenue, Building 80, 4th Floor, San Francisco, CA, 94110, USA
| | - Joel M Palefsky
- Division of Infectious Diseases, Department of Medicine, University of California at San Francisco, San Francisco, CA, USA.
- , 513 Parnassus Ave, Med Sci Room 420E, Box 0654, San Francisco, CA, 94143, USA.
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8
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Abstract
Anal cancer is a rare condition, although its incidence has been increasing over the past several decades, particularly in women. The majority of anal cancers are squamous cell cancers and are linked with human papilloma virus (HPV) infection. Recent work in HPV basic science has delineated the mechanism by which the virus leads to the development of anal cancer. With widespread availability of an HPV vaccine since 2006, vaccination has become an important strategy for anal cancer prevention. However, in the US, there remain no guidelines for anal cancer screening. Treatment of anal cancer is dictated largely by accurate staging, which is generally accomplished with a combination of physical exam, magnetic resonance imaging, computed tomography, and positron emission tomography. Chemoradiation remains the mainstay of treatment for most patients, with surgery reserved for salvage therapy. Recent trials have identified the optimal use of available chemotherapeutics. Exciting developments in immune therapies targeting HPV oncoproteins as well as therapeutic vaccines may soon dramatically change the way patients with anal cancer are managed.
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Affiliation(s)
- Matthew M. Symer
- New York-Presbyterian Hospital/Weill Cornell Medicine, Department of Surgery, 525 East 68th Street, New York, NY 10065, USA
| | - Heather L. Yeo
- New York-Presbyterian Hospital/Weill Cornell Medicine, Department of Surgery, 525 East 68th Street, New York, NY 10065, USA
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9
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Wang CCJ, Sparano J, Palefsky JM. Human Immunodeficiency Virus/AIDS, Human Papillomavirus, and Anal Cancer. Surg Oncol Clin N Am 2018; 26:17-31. [PMID: 27889034 DOI: 10.1016/j.soc.2016.07.010] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Anal cancer is an increasingly common non-AIDS-defining cancer among individuals infected with the human immunodeficiency virus (HIV). It is associated with human papillomavirus (HPV). HPV16 is the most common genotype detected in anal cancers. The HPV types detected in anal cancer are included in the 9-valent vaccine. HPV vaccines have demonstrated efficacy in reducing anal precancerous lesions in HIV-infected individuals. Standard treatment has been fluorouracil and mitomycin (or cisplatin) plus radiation. Continued studies are needed to test new treatment strategies in HIV-infected patients with anal cancer to determine which treatment protocols provide the best therapeutic index.
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Affiliation(s)
- Chia-Ching J Wang
- Division of Hematology/Oncology, Department of Medicine, Zuckerberg San Francisco General Hospital, 995 Potrero Avenue, Building 80, 4th Floor, San Francisco, CA 94110, USA
| | - Joseph Sparano
- Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, 1695 Eastchester Road, Bronx, NY 10461, USA
| | - Joel M Palefsky
- Division of Infectious Diseases, Department of Medicine, University of California at San Francisco, 513 Parnassus Avenue, Medical Science Room 420E, Box 0654, San Francisco, CA 94143, USA.
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10
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Camandaroba MPG, de Araujo RLC, Silva VSE, de Mello CAL, Riechelmann RP. Treatment outcomes of patients with localized anal squamous cell carcinoma according to HIV infection: systematic review and meta-analysis. J Gastrointest Oncol 2018; 10:48-60. [PMID: 30788159 DOI: 10.21037/jgo.2018.10.08] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Background Definitive chemoradiation (CRT) is the standard treatment for localized squamous cell carcinoma of the anus (SCCA). Because most phase III trials in SCCA have excluded patients with HIV, the evidence on treatment outcomes of these patients is lacking. We performed a systematic review and meta-analysis on the efficacy and toxicity profiles of HIV-positive SCCA patients treated with definitive CRT. Methods The systematic search was conducted Embase, Medline, Cochrane Libary, Scopus, Lilacs and Opengrey, from inception until September 2017. Eligible studies were clinical trials, prospective or retrospective cohort studies. The main outcome variables were 3-year disease-free survival (DFS) and overall survival (OS) rates and frequency of grade 3 or 4 (G3/4) treatment-related toxicities, according to HIV status. Meta-analyses using pooled risk ratios were performed for binary outcomes from comparative studies from the antiretroviral therapy (HAART) era with the fixed effects model. Results Out of 3,951 studies, 40 were deemed eligible, with a total of 3,720 patients. One third (N=1,298; 34%) were HIV-positive and their median pre CRT CD4 count was 347 µm/L. HIV-positive patients presented higher risk of G3/4 cutaneous toxicities [risk ratio (RR) =1.34; 95% CI, 1.10-1.64; P=0.004; I2=77.7%], worse 3-year DFS rate (RR =1.32; 95% CI, 1.01-1.74; P=0.043; I2=52.19%), and 3-year OS rate (RR =1.77; 95% CI, 1.35-2.32; P<0.001; I2=6%). Conclusions Patients with localized SCCA and HIV infection treated with CRT tend to experience higher risk of toxicities and worse DFS and OS rates. Our findings suggest that future trials should be tailored to HIV-positive patients.
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Affiliation(s)
| | - Raphael Leonardo Cunha de Araujo
- Department of Digestive Surgery, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.,Department of Oncology, Americas Medical Service/Brazil, United Health Group, Sao Paulo, SP, Brazil
| | | | | | - Rachel P Riechelmann
- Department of Clinical Oncology, A.C. Camargo Cancer Center, Sao Paulo, SP, Brazil
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11
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Effect of CD4 Count on Treatment Toxicity and Tumor Recurrence in Human Immunodeficiency Virus-Positive Patients With Anal Cancer. Int J Radiat Oncol Biol Phys 2017; 100:478-485. [PMID: 29102276 DOI: 10.1016/j.ijrobp.2017.09.034] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Revised: 08/15/2017] [Accepted: 09/14/2017] [Indexed: 12/13/2022]
Abstract
PURPOSE To study the effects of immunosuppression on treatment toxicity, long-term cancer recurrence risk, and survival among human immunodeficiency virus (HIV)-positive anal cancer patients. METHODS AND MATERIALS From a nationwide retrospective cohort of veterans with anal cancer we identified 142 HIV-positive patients with stage I-III disease, diagnosed between 2000 and 2015 and treated with definitive-intent chemotherapy and radiation. We used regression models to study the impact of pretreatment CD4 counts and longitudinal posttreatment CD4 counts on outcomes including acute toxicity, long-term ostomy rates, cancer recurrence, cancer-specific survival, and overall survival. All models were adjusted for potential confounders. RESULTS The median pretreatment CD4 count was 375 cells/mm3, which dropped to 157 cells/mm3 after treatment. Each 100-cell/mm3 decrease in pretreatment CD4 count was associated with an increased risk of acute hematologic toxicity (odds ratio 1.19, 95% confidence interval [CI] 1.01-1.42, P=.04) and hospitalization for hematologic toxicity (odds ratio 1.24, 95% CI 1.00-1.54, P=.049) but not gastrointestinal toxicity, tumor recurrence, or cancer-specific mortality (P>.05). Each 100-cells/mm3 decrease in posttreatment CD4 count increased the risk of recurrence by 54% (hazard ratio 1.54, 95% CI 1.09-2.17, P=.01) and cancer mortality by 46% at a trend level (hazard ratio 1.46, 95% CI 0.99-2.14, P=.06). Neither pre- nor posttreatment CD4 count influenced long-term ostomy rates or overall survival (all P>.05). CONCLUSIONS Lower pretreatment CD4 counts were associated with acute hematologic toxicity, and lower posttreatment CD4 count levels were associated with an increased risk of tumor recurrence. These results suggest that immune surveillance may play an important role in long-term disease control in anal cancer.
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12
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Alongi F, Giaj-Levra N, Sciascia S, Fozza A, Fersino S, Fiorentino A, Mazzola R, Ricchetti F, Buglione M, Buonfrate D, Roccatello D, Ricardi U, Bisoffi Z. Radiotherapy in patients with HIV: current issues and review of the literature. Lancet Oncol 2017; 18:e379-e393. [PMID: 28677574 DOI: 10.1016/s1470-2045(17)30440-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Revised: 05/04/2017] [Accepted: 05/04/2017] [Indexed: 02/08/2023]
Abstract
Although the introduction of highly active antiretroviral therapy has radically improved the life expectancy of patients with HIV, HIV positivity is still considered a major barrier to oncological treatment for patients with cancer because of their worse prognosis and increased susceptibility to toxic effects compared with patients who are immunocompetent. The use of radiotherapy with or without chemotherapy, immunotherapy, or molecular targeted therapy is the standard of care for several cancers. These new drugs and substantial improvements in radiotherapy techniques, including intensity-modulated radiotherapy, image-guided radiotherapy, and stereotactic ablative radiotherapy, are optimising the feasibility of such anticancer treatments and are providing new opportunities for patients with cancer and HIV. In this Review, we discuss the role of radiotherapy, with or without chemotherapy or new drugs, in the treatment of cancer in patients with HIV, with a focus on the efficacy and tolerability of this approach on the basis of available evidence. Moreover, we analyse and discuss the biological basis of interactions between HIV and radiotherapy, evidence from preclinical studies, and immunomodulation by radiotherapy in the HIV setting.
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Affiliation(s)
- Filippo Alongi
- Radiation Oncology, Sacro Cuore Don Calabria Cancer Care Center, Negrar-Verona, Italy; University of Brescia, Brescia, Italy
| | - Niccolò Giaj-Levra
- Radiation Oncology, Sacro Cuore Don Calabria Cancer Care Center, Negrar-Verona, Italy; Department of Oncology, University of Turin, Torino, Italy.
| | - Savino Sciascia
- Department of Clinical and Biological Sciences, Centre of Research of Immunopathology and Rare Diseases-Coordinating Centre of Piemonte and Valle d'Aosta Network for Rare Disease, Torino, Italy
| | - Alessandra Fozza
- Radiation Oncology, Department of Oncology, Ospedale dell'Angelo, Mestre-Venezia, Italy
| | - Sergio Fersino
- Radiation Oncology, Sacro Cuore Don Calabria Cancer Care Center, Negrar-Verona, Italy
| | - Alba Fiorentino
- Radiation Oncology, Sacro Cuore Don Calabria Cancer Care Center, Negrar-Verona, Italy
| | - Rosario Mazzola
- Radiation Oncology, Sacro Cuore Don Calabria Cancer Care Center, Negrar-Verona, Italy
| | - Francesco Ricchetti
- Radiation Oncology, Sacro Cuore Don Calabria Cancer Care Center, Negrar-Verona, Italy
| | - Michela Buglione
- Radiation Oncology, University and Spedali Civili, Brescia, Italy
| | - Dora Buonfrate
- Centre for Tropical Diseases, Sacro Cuore Don Calabria Hospital, Negrar-Verona, Italy
| | - Dario Roccatello
- Department of Clinical and Biological Sciences, Centre of Research of Immunopathology and Rare Diseases-Coordinating Centre of Piemonte and Valle d'Aosta Network for Rare Disease, Torino, Italy
| | | | - Zeno Bisoffi
- Centre for Tropical Diseases, Sacro Cuore Don Calabria Hospital, Negrar-Verona, Italy
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Comparison of Toxicity and Treatment Outcomes in HIV-positive Versus HIV-negative Patients With Squamous Cell Carcinoma of the Anal Canal. Am J Clin Oncol 2017; 40:386-392. [DOI: 10.1097/coc.0000000000000172] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Sparano JA, Lee JY, Palefsky J, Henry DH, Wachsman W, Rajdev L, Aboulafia D, Ratner L, Fitzgerald TJ, Kachnic L, Mitsuyasu R. Cetuximab Plus Chemoradiotherapy for HIV-Associated Anal Carcinoma: A Phase II AIDS Malignancy Consortium Trial. J Clin Oncol 2016; 35:727-733. [PMID: 27937092 DOI: 10.1200/jco.2016.69.1642] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
Purpose Squamous cell carcinoma of the anal canal (SCCAC) is characterized by high locoregional failure (LRF) rates after definitive chemoradiation (CRT), associated with anogenital human papilloma virus, and often appears in HIV infection. Because cetuximab enhances the effect of radiation therapy in human papilloma virus-associated oropharyngeal SCC, we hypothesized that adding cetuximab to CRT would reduce LRF in SCCAC. Methods Forty-five patients with stage I to III SCCAC and HIV infection received CRT: 45 to 54 Gy radiation therapy to the primary tumor and regional lymph nodes plus eight once-weekly doses of concurrent cetuximab and two cycles of cisplatin and fluorouracil. The study was designed to detect at least a 50% reduction in 3-year LRF rate (one-sided α, 0.10; power, 90%), assuming a 35% LRF rate from historical data. Results The 3-year LRF rate was 42% (95% CI, 28% to 56%; one-sided P = .9) by binomial proportional estimate using the prespecified end point (LRF or alive without LRF and followed < 3 years), and 20% (95% CI, 10% to 37%) by Kaplan-Meier estimate in post hoc analysis using definitions and methods consistent with historical data. Three-year rates by Kaplan-Meier estimate were 72% (95% CI, 56% to 84%) for progression-free survival and 79% (95% CI, 63% to 89%) for overall survival. Grade 4 toxicity occurred in 26%, and 4% had treatment-associated deaths. Conclusion HIV-associated SCCAC is potentially curable with definitive CRT. Although addition of cetuximab may result in less LRF, the 20% recurrence and 26% grade 4 toxicity rates indicate the continued need for more-effective and less-toxic therapies.
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Affiliation(s)
- Joseph A Sparano
- Joseph A. Sparano and Lakshmi Rajdev, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Jeannette Y. Lee, University of Arkansas for Medical Sciences, Little Rock, AR; Joel Palefsky, University of California San Francisco, San Francisco; William Wachsman, University of California San Diego, San Diego; Ronald Mitsuyasu, University of California Los Angeles, Los Angeles, CA; David H. Henry, University of Pennsylvania, Philadelphia, PA; David Aboulafia, Virginia Mason Medical Center, Seattle, WA; Lee Ratner, Washington University, St Louis, MO; Thomas J. Fitzgerald, Quality Assurance Review Center, Providence, RI; and Lisa Kachnic, Boston University Medical Center, Boston, MA
| | - Jeannette Y Lee
- Joseph A. Sparano and Lakshmi Rajdev, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Jeannette Y. Lee, University of Arkansas for Medical Sciences, Little Rock, AR; Joel Palefsky, University of California San Francisco, San Francisco; William Wachsman, University of California San Diego, San Diego; Ronald Mitsuyasu, University of California Los Angeles, Los Angeles, CA; David H. Henry, University of Pennsylvania, Philadelphia, PA; David Aboulafia, Virginia Mason Medical Center, Seattle, WA; Lee Ratner, Washington University, St Louis, MO; Thomas J. Fitzgerald, Quality Assurance Review Center, Providence, RI; and Lisa Kachnic, Boston University Medical Center, Boston, MA
| | - Joel Palefsky
- Joseph A. Sparano and Lakshmi Rajdev, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Jeannette Y. Lee, University of Arkansas for Medical Sciences, Little Rock, AR; Joel Palefsky, University of California San Francisco, San Francisco; William Wachsman, University of California San Diego, San Diego; Ronald Mitsuyasu, University of California Los Angeles, Los Angeles, CA; David H. Henry, University of Pennsylvania, Philadelphia, PA; David Aboulafia, Virginia Mason Medical Center, Seattle, WA; Lee Ratner, Washington University, St Louis, MO; Thomas J. Fitzgerald, Quality Assurance Review Center, Providence, RI; and Lisa Kachnic, Boston University Medical Center, Boston, MA
| | - David H Henry
- Joseph A. Sparano and Lakshmi Rajdev, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Jeannette Y. Lee, University of Arkansas for Medical Sciences, Little Rock, AR; Joel Palefsky, University of California San Francisco, San Francisco; William Wachsman, University of California San Diego, San Diego; Ronald Mitsuyasu, University of California Los Angeles, Los Angeles, CA; David H. Henry, University of Pennsylvania, Philadelphia, PA; David Aboulafia, Virginia Mason Medical Center, Seattle, WA; Lee Ratner, Washington University, St Louis, MO; Thomas J. Fitzgerald, Quality Assurance Review Center, Providence, RI; and Lisa Kachnic, Boston University Medical Center, Boston, MA
| | - William Wachsman
- Joseph A. Sparano and Lakshmi Rajdev, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Jeannette Y. Lee, University of Arkansas for Medical Sciences, Little Rock, AR; Joel Palefsky, University of California San Francisco, San Francisco; William Wachsman, University of California San Diego, San Diego; Ronald Mitsuyasu, University of California Los Angeles, Los Angeles, CA; David H. Henry, University of Pennsylvania, Philadelphia, PA; David Aboulafia, Virginia Mason Medical Center, Seattle, WA; Lee Ratner, Washington University, St Louis, MO; Thomas J. Fitzgerald, Quality Assurance Review Center, Providence, RI; and Lisa Kachnic, Boston University Medical Center, Boston, MA
| | - Lakshmi Rajdev
- Joseph A. Sparano and Lakshmi Rajdev, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Jeannette Y. Lee, University of Arkansas for Medical Sciences, Little Rock, AR; Joel Palefsky, University of California San Francisco, San Francisco; William Wachsman, University of California San Diego, San Diego; Ronald Mitsuyasu, University of California Los Angeles, Los Angeles, CA; David H. Henry, University of Pennsylvania, Philadelphia, PA; David Aboulafia, Virginia Mason Medical Center, Seattle, WA; Lee Ratner, Washington University, St Louis, MO; Thomas J. Fitzgerald, Quality Assurance Review Center, Providence, RI; and Lisa Kachnic, Boston University Medical Center, Boston, MA
| | - David Aboulafia
- Joseph A. Sparano and Lakshmi Rajdev, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Jeannette Y. Lee, University of Arkansas for Medical Sciences, Little Rock, AR; Joel Palefsky, University of California San Francisco, San Francisco; William Wachsman, University of California San Diego, San Diego; Ronald Mitsuyasu, University of California Los Angeles, Los Angeles, CA; David H. Henry, University of Pennsylvania, Philadelphia, PA; David Aboulafia, Virginia Mason Medical Center, Seattle, WA; Lee Ratner, Washington University, St Louis, MO; Thomas J. Fitzgerald, Quality Assurance Review Center, Providence, RI; and Lisa Kachnic, Boston University Medical Center, Boston, MA
| | - Lee Ratner
- Joseph A. Sparano and Lakshmi Rajdev, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Jeannette Y. Lee, University of Arkansas for Medical Sciences, Little Rock, AR; Joel Palefsky, University of California San Francisco, San Francisco; William Wachsman, University of California San Diego, San Diego; Ronald Mitsuyasu, University of California Los Angeles, Los Angeles, CA; David H. Henry, University of Pennsylvania, Philadelphia, PA; David Aboulafia, Virginia Mason Medical Center, Seattle, WA; Lee Ratner, Washington University, St Louis, MO; Thomas J. Fitzgerald, Quality Assurance Review Center, Providence, RI; and Lisa Kachnic, Boston University Medical Center, Boston, MA
| | - Thomas J Fitzgerald
- Joseph A. Sparano and Lakshmi Rajdev, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Jeannette Y. Lee, University of Arkansas for Medical Sciences, Little Rock, AR; Joel Palefsky, University of California San Francisco, San Francisco; William Wachsman, University of California San Diego, San Diego; Ronald Mitsuyasu, University of California Los Angeles, Los Angeles, CA; David H. Henry, University of Pennsylvania, Philadelphia, PA; David Aboulafia, Virginia Mason Medical Center, Seattle, WA; Lee Ratner, Washington University, St Louis, MO; Thomas J. Fitzgerald, Quality Assurance Review Center, Providence, RI; and Lisa Kachnic, Boston University Medical Center, Boston, MA
| | - Lisa Kachnic
- Joseph A. Sparano and Lakshmi Rajdev, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Jeannette Y. Lee, University of Arkansas for Medical Sciences, Little Rock, AR; Joel Palefsky, University of California San Francisco, San Francisco; William Wachsman, University of California San Diego, San Diego; Ronald Mitsuyasu, University of California Los Angeles, Los Angeles, CA; David H. Henry, University of Pennsylvania, Philadelphia, PA; David Aboulafia, Virginia Mason Medical Center, Seattle, WA; Lee Ratner, Washington University, St Louis, MO; Thomas J. Fitzgerald, Quality Assurance Review Center, Providence, RI; and Lisa Kachnic, Boston University Medical Center, Boston, MA
| | - Ronald Mitsuyasu
- Joseph A. Sparano and Lakshmi Rajdev, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Jeannette Y. Lee, University of Arkansas for Medical Sciences, Little Rock, AR; Joel Palefsky, University of California San Francisco, San Francisco; William Wachsman, University of California San Diego, San Diego; Ronald Mitsuyasu, University of California Los Angeles, Los Angeles, CA; David H. Henry, University of Pennsylvania, Philadelphia, PA; David Aboulafia, Virginia Mason Medical Center, Seattle, WA; Lee Ratner, Washington University, St Louis, MO; Thomas J. Fitzgerald, Quality Assurance Review Center, Providence, RI; and Lisa Kachnic, Boston University Medical Center, Boston, MA
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HIV Infection Is Associated With Poor Outcomes for Patients With Anal Cancer in the Highly Active Antiretroviral Therapy Era. Dis Colon Rectum 2015; 58:1130-6. [PMID: 26544809 DOI: 10.1097/dcr.0000000000000476] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
BACKGROUND HIV status may affect outcomes after definitive chemoradiotherapy for anal cancer. OBJECTIVE Here, we report a large series in the highly active antiretroviral therapy era comparing outcomes between HIV-positive and HIV-negative patients with anal cancer. DESIGN This was a retrospective chart review. SETTINGS The study was conducted at an outpatient oncology clinic at large academic center. PATIENTS A total of 107 patients were reviewed, 39 HIV positive and 68 HIV negative. All of the patients underwent definitive chemoradiation for anal cancer. MAIN OUTCOME MEASURES Data on patient characteristics, treatment, toxicity, and outcomes were collected. Overall survival, colostomy-free survival, local recurrence-free survival, and distant metastasis-free survival were analyzed. RESULTS Median follow-up was 15 months. HIV-positive patients were younger (median, 52 vs 64 years; p < 0.001) and predominantly men (82% men vs 49% men; p = 0.001). There were no significant differences in T, N, or stage groups. HIV-positive patients had a significantly longer duration from biopsy to start of chemoradiation (mean number of days, 82 vs 54; p = 0.042). There were no differences in rates of acute toxicities including diarrhea, fatigue, or dermatitis. HIV-positive patients had significantly higher rates of hospitalization (33% vs 15%; p = 0.024). The 3-year overall survival rate was 42% in HIV-positive and 76% in HIV-negative patients (p = 0.037; HR, 2.335 (95% CI, 1.032-5.283)). Three-year colostomy-free survival was 67% in HIV-positive and 88% in HIV-negative patients (p = 0.036; HR, 3.231 (95% CI, 1.014-10.299)). Differences in overall survival rates were not significant on multivariate analysis. LIMITATIONS This study was limited by its retrospective design and small patient numbers. CONCLUSIONS In this cohort, HIV-positive patients had significantly worse overall and colostomy-free survival rates than HIV-negative patients. However, differences in survival were not significant on multivariate analysis. Additional studies are necessary to establish the etiology of this difference.
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Ghosn M, Kourie HR, Abdayem P, Antoun J, Nasr D. Anal cancer treatment: Current status and future perspectives. World J Gastroenterol 2015; 21:2294-2302. [PMID: 25741135 PMCID: PMC4342904 DOI: 10.3748/wjg.v21.i8.2294] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2014] [Revised: 10/24/2014] [Accepted: 12/22/2014] [Indexed: 02/07/2023] Open
Abstract
Anal cancers (AC) are relatively rare tumors. Their incidence is increasing, particularly among men who have sex with other men due to widespread infection by human papilloma virus. The majority of anal cancers are squamous cell carcinomas, and they are treated according to stage. In local and locally advanced AC, concomitant chemoradiation therapy based on mitomycin C and 5-Fluorouracil (5-FU) is the current best treatment, while metastatic AC, chemotherapy with 5-FU and cisplatin remains the gold standard. There are no indications for induction or maintenance therapies in locally advanced tumors. Many novel strategies, such as targeted therapies, vaccination, immunotherapy and photodynamic therapy are in clinical trials for the treatment of AC, with promising results in some indications.
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Eng C, Ahmed S. Optimal management of squamous cell carcinoma of the anal canal: where are we now? Expert Rev Anticancer Ther 2014; 14:877-86. [DOI: 10.1586/14737140.2014.919861] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
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Long-term effects of chemoradiotherapy for anal cancer in patients with HIV infection: oncological outcomes, immunological status, and the clinical course of the HIV disease. Dis Colon Rectum 2014; 57:423-31. [PMID: 24608297 DOI: 10.1097/dcr.0000000000000057] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Despite the increasing evidence for chemoradiotherapy as standard treatment for anal cancer in patients with HIV infection, there is still some uncertainty regarding increased toxicity and adverse effects on the immune status. OBJECTIVE We report the clinical outcome of 5-fluorouracil/mitomycin C-based concurrent chemoradiotherapy for anal carcinoma in patients with HIV infection with an emphasis on the long-term course of CD4 counts and the HIV-related morbidity during follow-up. DESIGN AND SETTINGS A retrospective single-institution chart review was performed. PATIENTS Between 1997 and 2012, 36 HIV-positive patients were treated with standard chemoradiotherapy (median tumor dose, 54 (range, 50.4-60.4) Gy at 1.8 Gy/fraction; 5-fluorouracil, 800-1000 mg/m(2), days 1-4 or 1-5; mitomycin C, 10 mg/m(2), day 1, in the first and fifth week). MAIN OUTCOME MEASURES A retrospective analysis was performed with respect to tumor response, local control, cancer and overall survival, and toxicity. Immunological parameters, including pre- and posttreatment CD4 counts, viral load, and HIV-specific morbidity were recorded during follow-up. RESULTS Chemoradiotherapy could be completed in all patients. Acute grade 3 toxicities occurred in 17/36 patients (47%). Complete response was achieved in 31 patients (86%). Five-year local control, colostomy-free, cancer-specific, and overall survival were 72%, 87%, 77%, and 74%. The median pretreatment CD4 count significantly decreased from 367 cells/μL to 139 cells/μL, 3 to 7 weeks after completion of chemoradiotherapy (p < 0.001). Four patients (11%) experienced opportunistic illnesses during the follow-up (median, 66; range, 10-164 months). LIMITATIONS This study is limited by its retrospective design and its small sample size. CONCLUSIONS Our data confirm again that, in the highly active antiretroviral therapy era, anal cancer can be treated in HIV-positive patients with standard chemoradiotherapy, with a clinical outcome similar to their HIV-negative counterparts. The chemoradiotherapy-related decline of the CD4 counts, which remain decreased up to 6 years after chemoradiotherapy, was not associated with increased HIV-related clinical morbidity.
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Abstract
Anal cancer accounts for only 1.5% of gastrointestinal malignancies but this disease has shown a steady increase in incidence particularly in HIV positive males. The understanding of pathophysiology and treatment of anal cancer has changed radically over last thirty years. Risk factors have been identified and organ preservation by chemoradiotherapy has become a standard. This article aims to review the clinical presentation, diagnostic evaluation, and treatment options for anal cancer in the light of current literature.
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Affiliation(s)
- Sajad Ahmad Salati
- Department of Surgery, College of Medicine, Qassim University, Qassim, Kingdom of Saudi Arabia
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Poggio JL. Premalignant lesions of the anal canal and squamous cell carcinoma of the anal canal. Clin Colon Rectal Surg 2012; 24:177-92. [PMID: 22942800 DOI: 10.1055/s-0031-1286002] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Squamous cell carcinoma of the anus (SCCA) is a rare tumor. However, its incidence has been increasing in men and women over the past 25 years worldwide. Risk factors associated with this cancer are those behaviors that predispose individuals to human papillomavirus (HPV) infection and immunosuppression. Anal cancer is generally preceded by high-grade anal intraepithelial neoplasia (HGAIN), which is most prevalent in human immunodeficiency virus-positive men who have sex with men. High-risk patients may benefit from screening. The most common presentation is rectal bleeding, which is present in nearly 50% of patients. Twenty percent of patients have no symptoms at the time of presentation. Clinical staging of anal cancer requires a digital rectal exam and a positron emission tomography/computed tomography scan of the chest, abdomen, and pelvis. Endorectal/endoanal ultrasound appears to add more-specific staging information when compared with digital rectal examination alone. Treatment of anal cancer prior to the 1970s involved an abdominoperineal resection. However, the current standard of care for localized anal cancer is concurrent chemoradiation therapy, primarily because of its sphincter-saving and colostomy-sparing potential. Studies have addressed alternative chemoradiation regimens to improve the standard protocol of fluorouracil, misogynic, and radiation, but no alternative regimen has proven superior. Surgery is reserved for those patients with residual disease or recurrence.
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Alfa-Wali M, Allen-Mersh T, Antoniou A, Tait D, Newsom-Davis T, Gazzard B, Nelson M, Bower M. Chemoradiotherapy for anal cancer in HIV patients causes prolonged CD4 cell count suppression. Ann Oncol 2012; 23:141-147. [PMID: 21444358 DOI: 10.1093/annonc/mdr050] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Despite the advent of highly active antiretroviral therapy, anal cancer remains a significant health problem in human immunodeficiency virus (HIV) patients. We present the clinical features and treatment outcomes of anal cancer in 60 HIV-positive patients over a 20-year period. PATIENTS AND METHODS A prospective database of all HIV-positive individuals managed in a specialist unit since 1986 includes 11 112 patients (71 687 person-years of follow-up). Sixty patients with anal cancer were identified. Their clinicopathological and treatment details were analysed. RESULTS At anal cancer diagnosis, the mean age was 44 years (range: 28-75 years) and the median CD4 cell count was 305 mm(-3) (range: 16-1252 mm(-3)). Fifty (83%) had chemoradiotherapy (CRT). Forty-six (92%) responded, of whom 10 (22%) subsequently relapsed with locoregional (70%), metastatic disease (10%) or both (20%). The overall 5-year survival is 65% (95% confidence interval 51% to 78%). The median CD4 count fell from 289 mm(-3) before CRT to 132 mm(-3) after 3 months and to 189 mm(-3) after 1 year (P<0.05). Six patients in remission of anal cancer died of acquired immunodeficiency syndrome defining illnesses. CONCLUSIONS The management of anal cancer with CRT achieves similar outcomes as the general population. CRT is associated with significant prolonged CD4 suppression that may contribute to late deaths of patients in remission.
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Affiliation(s)
- M Alfa-Wali
- Department of Surgery and Cancer, Imperial College London, London
| | - T Allen-Mersh
- Department of Surgery and Cancer, Imperial College London, London
| | - A Antoniou
- Department of Surgery and Cancer, Imperial College London, London; Department of Surgery, Institute of Cancer Research, London
| | - D Tait
- Department of Clinical Oncology, Royal Marsden Hospital
| | - T Newsom-Davis
- Departments of Oncology; HIV Medicine, Chelsea and Westminster Hospital, London, UK
| | - B Gazzard
- Departments of Oncology; HIV Medicine, Chelsea and Westminster Hospital, London, UK
| | - M Nelson
- Departments of Oncology; HIV Medicine, Chelsea and Westminster Hospital, London, UK
| | - M Bower
- Department of Surgery and Cancer, Imperial College London, London; Departments of Oncology; HIV Medicine, Chelsea and Westminster Hospital, London, UK.
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Nguyen ML, Farrell KJ, Gunthel CJ. Non-AIDS-Defining Malignancies in Patients with HIV in the HAART Era. Curr Infect Dis Rep 2011; 12:46-55. [PMID: 21308498 DOI: 10.1007/s11908-009-0075-6] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The introduction of highly active antiretroviral therapy (HAART) has drastically changed the scope and spectrum of diseases associated with HIV, shifting from AIDS-related to non-AIDS-related diseases. Studies linking HIV/AIDS databases to cancer registries have shown a dramatic decrease in AIDS-related malignancies and a steady increase in non-AIDS-defining malignancies (NADM). We review the causes underlying the rise in incidence of NADM and the clinical presentation, pathology, and treatment outcomes of the four most commonly encountered NADM in the HAART era. Meta-analysis of published studies show an increase in NADM over the general population, mostly among infection-related cancers such as anal cancer, Hodgkin lymphoma, and liver cancer. Among the non-infection-related cancers, lung and skin cancers predominate. The overall effect of HAART on NADM is unsettled. As HIV-infected individuals survive longer, better screening strategies are needed to detect cancer earlier, and prospective data are needed to assess the impact of HAART on cancer outcomes.
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Affiliation(s)
- Minh Ly Nguyen
- Emory University School of Medicine, 341 Ponce de Leon NE, Atlanta, GA, 30308, USA,
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Gervaz P, Calmy A, Durmishi Y, Allal AS, Morel P. Squamous cell carcinoma of the anus-an opportunistic cancer in HIV-positive male homosexuals. World J Gastroenterol 2011; 17:2987-91. [PMID: 21799644 PMCID: PMC3132249 DOI: 10.3748/wjg.v17.i25.2987] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2010] [Revised: 12/10/2010] [Accepted: 12/17/2010] [Indexed: 02/06/2023] Open
Abstract
Squamous cell carcinoma of the anus (SCCA) is a common cancer in the human immunodeficiency virus (HIV)-infected population, and its incidence continues to increase in male homosexuals. Combined chemoradiation with mitomycin C and 5-fluorouracil was poorly tolerated by severely immunocompromised patients in the early 1990s. In the era of highly active antiretroviral therapy (HAART), however, recent data indicate that: (1) most HIV patients with anal cancer can tolerate standard chemotherapy regimens; and (2) this approach is associated with survival rates similar to those of HIV-negative patients. However, HIV-positive patients with SCCA are much younger, more likely to develop local tumor recurrence, and ultimately die from anal cancer than immune competent patients. Taken together, these findings suggest that anal cancer is an often fatal neoplasia in middle-aged HIV-positive male homosexuals. In this population, SCCA is an opportunistic disease resulting in patients with suboptimal immune function from persistent infection and prolonged exposition to oncogenic human papillomaviruses (HPVs). Large-scale cancer-prevention strategies (routine anuscopy and anal papanicolaou testing) should be implemented in this population. In addition, definitive eradication of oncogenic HPVs within the anogenital mucosa of high-risk individuals might require a proactive approach with repeated vaccination.
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Squamous cell cancer of the anal canal in HIV-infected patients receiving highly active antiretroviral therapy: a single institution experience. Am J Clin Oncol 2011; 34:135-9. [PMID: 20523206 DOI: 10.1097/coc.0b013e3181dbb710] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
BACKGROUND Human immunodeficiency virus (HIV)-infected patients are at increased risk for squamous cell carcinoma of the anal canal (SCCA) and the incidence of SCCA has increased in the era of highly active antiretroviral therapy. The outcome of SCCA in HIV-positive patients has not been evaluated in prospective trials and the published literature is limited to retrospective case series. The aim of this study is to describe the treatment, toxicity, and overall survival (OS) in patients with and without HIV infection. METHODS We performed a retrospective chart review of all patients treated for invasive SCCA at Karmanos Cancer Institute, Wayne State University from 1991 to 2007 and collected data regarding HIV status, demographics, stage at diagnosis, treatment, response to treatment, toxicity, and survival. RESULTS Forty-five patients with SCCA were identified, of whom 13 were HIV-positive and 32 were HIV-negative. HIV-positive patients were younger (median age, 45 vs. 57 years) and had a higher frequency of men (89% vs. 37%). Patients were balanced for presenting stage at diagnosis and rates of local recurrence were found to be similar between the 2 groups. HIV-positive patients were less likely to receive full dose chemoradiotherapy. Except for dermatitis, the incidence of grade 3 to 4 toxicities was similar in both groups. Median OS was 33.5 months for HIV-positive patients and 71.8 months for HIV-negative patients. Although limited by the small size of the study, the OS was not statistically significantly different by HIV status (P = 0.787). CONCLUSION Although the HIV-positive patients received lower dose chemoradiotherapy, no major difference in local control or overall survival was observed.
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See AP, Zeng J, Tran PT, Lim M. Acute toxicity of second generation HIV protease-inhibitors in combination with radiotherapy: a retrospective case series. Radiat Oncol 2011; 6:25. [PMID: 21414215 PMCID: PMC3064638 DOI: 10.1186/1748-717x-6-25] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2010] [Accepted: 03/17/2011] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND There is little data on the safety of combining radiation therapy and human immunodeficiency virus (HIV) protease inhibitors to treat cancers in HIV-positive patients. We describe acute toxicities observed in a series of HIV-positive patients receiving modern radiation treatments, and compare patients receiving HIV protease inhibitors (PI) with patients not receiving HIV PIs. METHODS By reviewing the clinical records beginning January 1, 2009 from the radiation oncology department, we identified 29 HIV-positive patients who received radiation therapy to 34 body sites. Baseline information, treatment regimen, and toxicities were documented by review of medical records: patient age, histology and source of the primary tumor, HIV medication regimen, pre-radiation CD4 count, systemic chemotherapy, radiation therapy dose and fractionation, irradiated body region, toxicities, and duration of follow-up. Patients were grouped according to whether they received concurrent HIV PIs and compared using Pearson's chi-square test. RESULTS At baseline, the patients in the two groups were similar with the exception of HIV medication regimens, CD4 count and presence of AIDS-defining malignancy. Patients taking concurrent PIs were more likely to be taking other HIV medications (p = 0.001) and have CD4 count >500 (p = 0.006). Patients taking PIs were borderline less likely to have an AIDS-defining malignancy (p = 0.06). After radiation treatment, 100 acute toxicities were observed and were equally common in both groups (64 [median 3 per patient, IQR 1-7] with PIs; 36 [median 3 per patient, IQR 2-3] without PIs). The observed toxicities were also equally severe in the two groups (Grades I, II, III respectively: 30, 30, 4 with PIs; 23, 13, 0 without PIs: p = 0.38). There were two cases that were stopped early, one in each group; these were not attributable to toxicity. CONCLUSIONS In this study of recent radiotherapy in HIV-positive patients taking second generation PIs, no difference in toxicities was observed in patients taking PIs compared to patients not taking PIs during radiation therapy. This suggests that it is safe to use unmodified doses of PIs and radiation therapy in HIV cancer patients, and that it is feasible to use PIs as a radiosensitizer in cancer therapy, as has been suggested by pre-clinical results.
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Affiliation(s)
- Alfred P See
- Department of Radiation Oncology and Molecular Radiation Sciences, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Hospital, Baltimore, MD 21231, USA
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Fraunholz I, Rabeneck D, Gerstein J, Jäck K, Haberl A, Weiss C, Rödel C. Concurrent chemoradiotherapy with 5-fluorouracil and mitomycin C for anal carcinoma: are there differences between HIV-positive and HIV-negative patients in the era of highly active antiretroviral therapy? Radiother Oncol 2010; 98:99-104. [PMID: 21168927 DOI: 10.1016/j.radonc.2010.11.011] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2009] [Revised: 11/05/2010] [Accepted: 11/18/2010] [Indexed: 01/11/2023]
Abstract
PURPOSE To report treatment compliance, toxicity and clinical outcome of chemoradiotherapy (CRT) for anal carcinoma in HIV-negative vs. HIV-positive patients treated with highly active antiretroviral therapy. MATERIAL AND METHODS Between 1997 and 2008, 25 HIV-positive and 45 HIV-negative patients received CRT (50.4 Gy at 1.8 Gy/fraction plus 5.4-10.8 Gy boost; 5-fluorouracil, 1000 mg/m(2), Days 1-4 and 29-32, mitomycin C, 10 mg/m(2), Days 1 and 29). Median follow-up was 51 (range, 3-235) months. RESULTS HIV-positive patients were significantly younger (mean age, 47 vs. 57 years, p<0.001) and predominantly male (92% vs. 29%, p<0.001). CRT could be completed in all patients with a reduction of chemotherapy and/or RT-interruption in 28% and 8%, respectively, in HIV-positive patients, and in 9% and 11%, respectively, in HIV-negative patients. Acute Grade 3/4-toxicity occurred in 44% vs. 49% (p=0.79). Initial complete response (84% vs. 93%, p=0.41), 5-year rates of local control (65% vs. 78%, p=0.44), cancer-specific (78% vs. 90%, p=0.17) and overall survival (71% vs. 77%, p=0.76) were not significantly different. CONCLUSION HIV-positive patients with anal cancer can be treated with standard CRT, with the same tolerability and toxicity as HIV-negative patients. Long-term local control and survival rates are not significantly different between these groups.
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Affiliation(s)
- Ingeborg Fraunholz
- Department of Radiation Oncology, Johann Wolfgang Goethe-University, Frankfurt/Main, Germany.
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Lampejo T, Kavanagh D, Clark J, Goldin R, Osborn M, Ziprin P, Cleator S. Prognostic biomarkers in squamous cell carcinoma of the anus: a systematic review. Br J Cancer 2010; 103:1858-69. [PMID: 21063399 PMCID: PMC3008609 DOI: 10.1038/sj.bjc.6605984] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND recent decades have seen combination chemoradiotherapy become the standard treatment for anal squamous cell carcinoma (SCC). However, the burden of this disease continues to rise, with only 10% of patients with metastatic disease surviving >2 years. Further insight into tumour characteristics and molecular biology may identify novel therapeutic targets. This systematic review examines current prognostic markers in SCC of the anus. METHODS an extensive literature search was performed to identify studies reporting on biomarkers in anal cancer in the context of clinical outcome following treatment primarily with chemoradiotherapy. RESULTS in all, 21 studies were included. A total of 29 biomarkers were studied belonging to 9 different functional classes. Of these biomarkers, 13 were found to have an association with outcome in at least one study. The tumour-suppressor genes p53 and p21 were the only markers shown to be of prognostic value in more than one study. CONCLUSIONS an array of biomarkers have been identified that correlate with survival following chemoradiotherapy in anal cancer. However, investigators are yet to identify a biomarker that has the ability to consistently predict outcome in this disease. Further studies are needed to elucidate whether these candidate biomarkers demonstrate their optimum value when they serve as targets for new therapeutic strategies.
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Affiliation(s)
- T Lampejo
- Department of Biosurgery and Surgical Technology, Imperial College London, St Mary's Hospital, Praed Street, London, W2 1NY, UK.
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Blumetti J, Bastawrous AL. Epidermoid cancers of the anal canal: current treatment. Clin Colon Rectal Surg 2010; 22:77-83. [PMID: 20436831 DOI: 10.1055/s-0029-1223838] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Epidermoid carcinoma of the anal canal is an uncommon disease, but has increased in incidence with the HIV epidemic. Prior to the 1970s, treatment consisted of radical surgery with abdominoperineal resection. With the pioneering work of Dr. Norman Nigro, this has shifted to a nonsurgical approach, with primary treatment consisting of multimodality therapy with radiation and chemotherapy. This review provides an overview of the historical, current, and future treatments of epidermoid anal canal malignancies.
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Affiliation(s)
- Jennifer Blumetti
- Division of Colon and Rectal Surgery, Department of Surgery, University of Illinois at Chicago, Chicago, Illinois, USA
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Sanfilippo NJ, Mitchell J, Grew D, DeLacure M. Toxicity of head-and-neck radiation therapy in human immunodeficiency virus-positive patients. Int J Radiat Oncol Biol Phys 2010; 77:1375-9. [PMID: 20097488 DOI: 10.1016/j.ijrobp.2009.06.087] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2009] [Revised: 06/11/2009] [Accepted: 06/18/2009] [Indexed: 10/19/2022]
Abstract
PURPOSE To examine the acute morbidity of high dose head and neck RT and CRT in patients with infected with HIV. METHODS AND MATERIALS All HIV-positive patients who underwent radiation therapy for head and neck cancer in our department between 2004 and 2008 were reviewed. Treatment related data were examined. All treatments were delivered with megavoltage photon beams or electron beams. Patients were evaluated by an attending radiation oncologist for toxicity and response on a weekly basis during therapy and monthly after treatment in a multidisciplinary clinic. Acute toxicities were recorded using the Radiation Therapy and Oncology Group (RTOG) common toxicity criteria. Response to treatment was based on both physical exam as well as post-treatment imaging as indicated. RESULTS Thirteen patients who underwent RT with a diagnosis of HIV were identified. Median age was 53 years and median follow-up was 22 months. Twelve had squamous cell carcinoma and one had lymphoproliferative parotiditis. Median radiation dose was 66.4 Gy and median duration of treatment was 51 days. The median number of scheduled radiotherapy days missed was zero (range 0 to 7). One patient (8%) developed Grade 4 confluent moist desquamation. Eight patients (61%) developed Grade 3 toxicity. CONCLUSION Based on our results, HIV-positive individuals appear to tolerate treatment for head and neck cancer, with toxicity similar to that in HIV-negative individuals.
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Affiliation(s)
- Nicholas J Sanfilippo
- Department of Radiation Oncology, New York University School of Medicine, New York, NY 10016, USA.
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Khanna N. HAART use in women with HIV and influence on cervical intraepithelial neoplasia: a clinical opinion. J Low Genit Tract Dis 2009; 6:111-5. [PMID: 17051009 DOI: 10.1097/00128360-200204000-00007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVES Study the role of highly active antiretroviral therapy (HAART) in cervical disease in women with human immunodeficiency virus (HIV) and human papillomavirus (HPV) infections. MATERIALS AND METHODS A systematic review of current literature and the results summarized in the following headings: HIV and cytological evidence of disease, HIV and HPV, and HAART and HIV in women with HPV-associated cervical disease. RESULTS Limited data is available to study the influence of HAART on HPV-related cervical disease in women with HIV. There is evidence that the use of HAART may lead to immune restoration and thereby prevent severe recurrent HPV disease, thus influencing associated cervical disease. CONCLUSIONS Little data is available on HAART and its role in HPV-associated cervical disease in women with HIV. Immune restoration may decrease the severity and recurrence of HPV infection and potentially impact cervical disease. Population-based studies are needed to further evaluate the role of HAART in HPV associated cervical disease.
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Affiliation(s)
- Niharika Khanna
- Department of Family Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
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Barriger RB, Calley C, Cárdenes HR. Treatment of anal carcinoma in immune-compromised patients. Clin Transl Oncol 2009; 11:609-14. [PMID: 19776001 DOI: 10.1007/s12094-009-0412-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Immune-compromised populations show an increased incidence of anogenital tract neoplasms. This study was undertaken to evaluate local control (LC), overall survival (OS) and toxicity in immune-compromised patients with anal carcinoma treated with radiotherapy with or without chemotherapy. METHODS We identified 25 patients with anal carcinoma and human immunodeficiency virus (HIV) infection or history of solid-organ transplant on chronic medical immune-suppression. Median age and follow-up were 44 years and 26 months respectively. AJCC T-stages were Tis (4%), T1 (8%), T2 (58%) and T3 (29%). N-stages were N0 (79%), N1 (4%), N2 (13%) and N3 (4%). One patient had metastatic disease at diagnosis. Seventy-five percent received concurrent chemoradiotherapy. Median radiation dose to the primary tumour was 50 Gy. RESULTS One-, 3- and 5-year LC without salvage therapy was 87%, 87% and 70% respectively. One-, 3- and 5-year actuarial OS was 96%, 73% and 61% respectively. One-, 3- and 5-year OS was 100% for treatment time (TT) <50 days and 57%, 38% and 0% for TT > or =50 days (p=0.0009). All patients had acute grade 2-3 skin toxicity. Acute grade 3-4 gastrointestinal (GI), genitourinary (GU) and haematological toxicity occurred in 8%, 0% and 38%. Late grade 3-4 skin, GI and GU toxicity occurred in 8%, 4% and 0%. CONCLUSIONS Most HIV-positive and organ transplant patients receiving radiotherapy with or without chemotherapy experience acute toxicity but few have chronic complications. T-stage and CD4 level in HIV-positive patients predict for LC. T-stage and TT predict for OS.
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Affiliation(s)
- Robert Bryan Barriger
- Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
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Fraunholz I, Weiss C, Eberlein K, Haberl A, Rödel C. Concurrent chemoradiotherapy with 5-fluorouracil and mitomycin C for invasive anal carcinoma in human immunodeficiency virus-positive patients receiving highly active antiretroviral therapy. Int J Radiat Oncol Biol Phys 2009; 76:1425-32. [PMID: 19744801 DOI: 10.1016/j.ijrobp.2009.03.060] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2009] [Revised: 03/27/2009] [Accepted: 03/29/2009] [Indexed: 10/20/2022]
Abstract
PURPOSE To report the clinical outcomes of chemoradiotherapy (CRT) for anal carcinoma in human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy. PATIENTS AND METHODS Between 1997 and 2008, 21 HIV-positive patients who were receiving highly active antiretroviral therapy were treated with CRT (50.4 Gy at 1.8 Gy/fraction plus a 5.4-10.8-Gy external boost; 5-fluorouracil, 1,000 mg/m(2), Days 1-4 and 29-32; and mitomycin C, 10 mg/m(2), Days 1 and 29). A retrospective analysis was performed with respect to the tumor response, local control, cancer-specific and overall survival, and toxicity. The immunologic parameters, including pre- and post-treatment CD4 count, viral load, and acquired immunodeficiency syndrome-specific morbidity was recorded during follow-up (median, 53 months; range, 10-99). RESULTS CRT could be completed in all 21 patients with a reduction in the chemotherapy dose and/or interruption of radiotherapy in 5 and 5 cases, respectively. Acute Grade 3 toxicity occurred in 8 (38%) of the 21 patients. A complete response was achieved in 17 patients (81%), and tumor persistence or early progression was noted in 4 (19%). Six patients (29%) died, 5 of cancer progression and 1 of treatment-related toxicity. The 5-year local control, cancer-specific, and overall survival rate was 59%, 75%, and 67%, respectively. The median CD4 count significantly decreased from 347.5 cells/microL before CRT to 125 cells/microL 3-7 weeks after CRT completion (p <.001). In 6 (32%) of 19 patients, an increase of the HIV viral load was noted. Both parameters returned to the pretreatment values with additional follow-up. CONCLUSION Our data have confirmed that in the highly active antiretroviral therapy era, HIV-related anal cancer can be treated with standard CRT without dose reductions. Close surveillance of the immunologic parameters is necessary.
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Affiliation(s)
- Ingeborg Fraunholz
- Department of Radiation Oncology, Johann Wolfgang Goethe-University, Frankfurt/Main, Germany.
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Abramowitz L, Mathieu N, Roudot-Thoraval F, Lemarchand N, Bauer P, Hennequin C, Mitry E, Romelaer C, Aparicio T, Sobhani I. Epidermoid anal cancer prognosis comparison among HIV+ and HIV- patients. Aliment Pharmacol Ther 2009; 30:414-21. [PMID: 19392867 DOI: 10.1111/j.1365-2036.2009.04026.x] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
Abstract
BACKGROUND Previous studies suggest a poor prognosis of epidermoid anal cancer in HIV+ patients. AIM To investigate the long-term outcome of epidermoid anal cancer in HIV+ and HIV- patients in the highly active antiretroviral treatment (HAART) era. METHODS We included all patients with epidermoid anal cancer referred to six hospitals from 1998 to 2004. RESULTS In all, 151 patients (44 HIV+, 107 HIV-) were reviewed retrospectively for 27 (median of 16-44) months. HIV+ patients were male (100% vs. 27%, P < 0.001) and younger (45 vs. 62 years old, P < 0.001) than HIV- patients. No significant differences were observed in the tumour stage, pelvic radiotherapy dose or concomitant chemotherapy, according to the HIV status. After chemoradiotherapy, similar numbers of HIV+ and HIV- patients had grade III-IV toxicity. A complete response was obtained in 82% and 75% (N.S.) of cases, respectively. The disease-free survival rates were 77% and 67% (N.S.) and the overall survival rates were 85% and 84% (N.S.), respectively, after 3 years of follow-up. Duration of HIV infection, viral load and CD4 count had no effect on the survival rate of HIV+ patients with EAC. CONCLUSIONS The clinical outcome of HIV+ patients with epidermoid anal cancer is similar to that of HIV- patients. Therefore, the same therapeutic guidelines should be applied to both populations.
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Affiliation(s)
- L Abramowitz
- AP-HP, Service de gastroentérologie et Unité de proctologie medico-chirurgicale, Hôpital Universitaire Bichat, Paris, CEDEX, France.
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Abstract
PURPOSE The purpose of this study is to identify the effect of HIV status on outcome of treatment for squamous-cell carcinoma of the anal canal. METHODS A retrospective review was performed on all patients with squamous-cell carcinoma of the anal canal treated at a single academic institution between January 1996 and December 2006. RESULTS Our search identified 87 (21 HIV-positive) patients who had invasive squamous-cell cancer. The median follow-up was 38 months. Eighty-five percent of HIV-negative patients and 81 percent of HIV-positive were identified as complete responders at 6 weeks after completion of combined modality therapy. Eight percent of HIV-negative and 29 percent of HIV-positive patients developed recurrent disease after 6 months (P = 0.0009). Overall survival for HIV-negative and HIV-positive patients was 71 percent and 73 percent, respectively. CONCLUSIONS HIV-positive patients respond equally to combined modality therapy but have recurrences more frequently than patients who are HIV negative. Overall survival in these two groups is equivalent.
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37
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Zhang Q, Abitbol AA. Cancer of the Anal Canal. Radiat Oncol 2008. [DOI: 10.1007/978-3-540-77385-6_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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Rouquie D, Lasser P, Castaing M, Boige V, Goéré D, Pignon JP, Ducreux M, Elias D, Pocard M. Résection R0, seul facteur pronostique dans les amputations abdominopérinéales de rattrapage des cancers du canal anal (série consécutive de 95 patients). ACTA ACUST UNITED AC 2008; 145:335-40. [DOI: 10.1016/s0021-7697(08)74312-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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Marked increase in the incidence of invasive anal cancer among HIV-infected patients despite treatment with combination antiretroviral therapy. AIDS 2008; 22:1203-11. [PMID: 18525266 DOI: 10.1097/qad.0b013e3283023f78] [Citation(s) in RCA: 203] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
OBJECTIVE To describe the cases of anal cancer that appeared in the French Hospital Database on HIV between 1992 and 2004 and to study risk factors of anal cancer. METHODS We examined the incidence rates of anal cancer between 1992 and 2004 and the risk associated among 86,322 HIV-infected patients included in the French Hospital Database on HIV. RESULTS We identified 132 cases of anal cancer, including 124 cases in men (94%), of whom 75% had sex with men. Median age at diagnosis was 42.8 years (interquartile range: 36.9-49.4). At diagnosis, 103 patients (78%) were receiving combination antiretroviral therapy for a median of 37.1 months (interquartile range: 4.5-59.8). Median survival after anal cancer diagnosis was 5 years. The respective overall incidence rates of anal cancer per 100,000 person-years between 1992 and March 1996, April 1996 to 1998 and between 1999 and 2004 were 11 (95% confidence interval, 4-17), 18 (95% confidence interval, 10-27) and 40 (95% confidence interval, 32-47). The risk of anal cancer was higher among men who have sex with men. After adjustment for age at inclusion in the study, as well as gender, the HIV transmission group, the nadir CD4 cell count and AIDS status, the incidence was higher in the years 1999-2004 than in between 1992 to March 1996 (hazard ratio, 2.5; 95% confidence interval, 1.2-5.3), with no change in the years 1999-2004. CONCLUSION The incidence of anal cancer has increased among HIV-infected patients in France since 1996. Although an ascertainment bias cannot be excluded, data indicate that combination antiretroviral therapy does not prevent anal cancer in these patients. This supports the urgent need for developing anal cancer screening programs for HIV-infected men who have sex with men.
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Chiao EY, Giordano TP, Richardson P, El-Serag HB. Human immunodeficiency virus-associated squamous cell cancer of the anus: epidemiology and outcomes in the highly active antiretroviral therapy era. J Clin Oncol 2008; 26:474-9. [PMID: 18202423 DOI: 10.1200/jco.2007.14.2810] [Citation(s) in RCA: 89] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
PURPOSE To evaluate and determine predictors of squamous cell carcinoma of the anus (SCCA) outcomes in the highly active antiretroviral therapy (HAART) era for HIV-positive and -negative individuals using large national Veterans Affairs (VA) Administration databases. PATIENTS AND METHODS We used the VA administrative databases to perform a retrospective cohort study in 1,184 veterans diagnosed with SCCA between 1998 and 2004. We calculated HIV infection rates and used logistic regression to identify epidemiologic factors that were associated with HIV infection. Kaplan-Meier curves and Cox proportional hazards models were calculated to compare survival between HIV-positive and HIV-negative veterans. RESULTS In our cohort, 175 patients (15%) were HIV positive. The median age of the HIV-negative and -positive patients was 63 and 49 years, respectively (P < .001). Individuals with HIV were eight times more likely to be male (P = .01) and three times more likely to be African American (P < .001). There were no differences between HIV-positive and HIV-negative individuals in the receipt of treatment. The 2-year observed survival rates were 77% and 75% among HIV-positive and HIV-negative individuals, respectively. In multivariate Cox analysis, significant predictors of survival were age, sex, metastasis at diagnosis, and comorbidity score. HIV infection did not affect survival. CONCLUSION A noteworthy proportion of individuals with SCCA in the VA system are HIV positive. HIV-associated SCCA seems mainly to be a disease among younger men. Survival of SCCA is equivalent between HIV-positive and HIV-negative individuals in the HAART era. Treatment should not be withheld or deintensified based on HIV status.
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Affiliation(s)
- Elizabeth Y Chiao
- Department of Medicine, Baylor College of Medicine, Houston Center for Quality of Care and Utilization Studies, Michael E. DeBakey Veterans Affairs Medical Center (152), 2002 Holcombe Blvd, Houston, TX 77030, USA.
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41
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Wexler A, Berson AM, Goldstone SE, Waltzman R, Penzer J, Maisonet OG, McDermott B, Rescigno J. Invasive anal squamous-cell carcinoma in the HIV-positive patient: outcome in the era of highly active antiretroviral therapy. Dis Colon Rectum 2008; 51:73-81. [PMID: 18066626 DOI: 10.1007/s10350-007-9154-7] [Citation(s) in RCA: 112] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2007] [Revised: 06/28/2007] [Accepted: 08/05/2007] [Indexed: 12/26/2022]
Abstract
INTRODUCTION The incidence of invasive anal squamous-cell carcinoma in patients with HIV is increasing. We report the outcome after combined chemoradiotherapy for anal squamous-cell carcinoma in HIV-infected individuals. METHODS Thirty-two HIV-positive patients treated at the St. Vincent's Cancer Care Center for anal squamous-cell carcinoma from 1997 through mid 2005 were reviewed retrospectively. All patients also received highly active antiretroviral therapy. Treatment consisted of radiotherapy concurrent with 5-fluorouracil and mitomycin C in most patients. Overall survival, anal cancer-specific survival, local recurrence, and toxicity were assessed. RESULTS Median time from completion of radiotherapy to last follow-up of surviving patients was 35 months. Five-year locoregional relapse, anal cancer-specific survival, and overall survival were 16 , 75, and 65 percent, respectively. In multivariate analysis, locoregional recurrence, cancer-specific survival, and overall survival were all significantly associated with tumor size. Overall survival was independently associated with high viral load and low CD4 count. Acute toxicity included: Grade 3 skin in 25 percent of patients, Grade 3 diarrhea: 28 percent, and Grade 3 or 4 hematologic toxicity in 21 and 48 percent, respectively. More than two-thirds of patients required radiotherapy interruption. There was no negative impact of chemoradiotherapy on viral load. CONCLUSIONS Outcome after chemoradiotherapy for HIV-related anal squamous-cell carcinoma in the era of highly active antiretroviral therapy is comparable to outcome in patients without HIV. However, significant toxicity is seen with standard treatment regimens. Earlier diagnosis and risk-adapted therapy could lead to improved survival and decreased treatment-related morbidity.
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Affiliation(s)
- Ann Wexler
- Department of Medicine, St. Vincent's Hospital, New York, NY, USA
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Abstract
Anal cancer is a rare tumor with an incidence that has been rising over the last 25 years. The disease was once thought to develop as a result of chronic irritation, but it is now known that this is not the case. Multiple risk factors, including human papillomavirus (HPV) infection, anoreceptive intercourse, cigarette smoking, and immunosuppression, have been identified. HIV infection is also associated with anal cancer; there is a higher incidence in HIV-positive patients but the direct relationship between HIV and anal cancer has been difficult to separate from the prevalence of HPV in this population. HIV infection is also associated with anal cancer; there are increasing numbers of HIV-positive patients being diagnosed with the disease. Treatment of anal cancer prior to the 1970s involved abdominoperineal resection, but the standard of care is now concurrent chemoradiation therapy, with surgery reserved for those patients with residual disease. We present a case of anal cancer followed by a general discussion of both risk factors and treatment.
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Affiliation(s)
- Hope E Uronis
- Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
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44
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Herat A, Whitfeld M, Hillman R. Anal intraepithelial neoplasia and anal cancer in dermatological practice. Australas J Dermatol 2007; 48:143-53; quiz 154-5. [PMID: 17680964 DOI: 10.1111/j.1440-0960.2007.00369.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Anal intraepithelial neoplasia is considered to be a precursor lesion of invasive anal cancer. It is now increasingly recognized in high-risk groups, such as men who have sex with men and HIV-infected patients. Human papillomaviruses are considered to be an important aetiological agent in both anal intraepithelial neoplasia and anal cancer. Dermatologists are likely to encounter these conditions among the differential diagnoses to be considered in high-risk patients presenting with perianal and anal lesions. Anal cancer rates are also increasing among the HIV-infected and HIV-non-infected population. The successful treatment of anal intraepithelial neoplasia may reduce the risk of subsequent development of anal cancer. However, current therapies for anal intraepithelial neoplasia may be associated with treatment-related morbidity and are not well validated. It is currently not proven that they reduce the likelihood of the development of anal cancer. Nevertheless, screening for anal intraepithelial neoplasia is being advocated for high-risk groups and may become standard dermatological care for these patients. In view of recent developments in the understanding of this condition, this article reviews the current understanding of anal intraepithelial neoplasia and its treatment from a dermatological perspective.
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Affiliation(s)
- Asoka Herat
- Skin and Cancer Foundation, Darlinghurst, New South Wales, Australia.
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45
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Cuneo KC, Tu T, Geng L, Fu A, Hallahan DE, Willey CD. HIV protease inhibitors enhance the efficacy of irradiation. Cancer Res 2007; 67:4886-93. [PMID: 17510418 DOI: 10.1158/0008-5472.can-06-3684] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Tumor vascular endothelium is rather resistant to the cytotoxic effects of radiation. The HIV protease inhibitors (HPI) amprenavir, nelfinavir, and saquinavir have previously been shown to sensitize tumor cells to the cytotoxic effects of radiation. Additionally, this class of drug has been shown to inhibit angiogenesis and tumor cell migration. Therefore, in the current study, we wanted to determine whether HPIs could enhance the effect of radiation on endothelial function. Our study shows that HPIs, particularly nelfinavir, significantly enhance radiations effect on human umbilical vein endothelial cells (HUVEC) and tumor vascular endothelium. We show that pretreatment of HUVEC with nelfinavir results in enhanced cytotoxicity, including increased apoptosis, when combined with radiation. Moreover, using several functional assays, we show that combination treatment effectively blocks endothelial cell migration and organization. These findings were accompanied by attenuation of Akt phosphorylation, a known pathway for radioresistance. Last, in vivo analysis of tumor microvasculature destruction showed a more than additive effect for nelfinavir and radiation. This study shows that HPIs can enhance the effect of ionizing radiation on vascular endothelium. Therefore, the Food and Drug Administration-approved drug, nelfinavir, may be an effective radiosensitizer in the clinic.
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Affiliation(s)
- Kyle C Cuneo
- Vanderbilt University School of Medicine, Nashville, Tennessee, USA
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Abstract
AIDS produces profound alterations in normal immunity. Impaired cellular immunity permits new tumor formation as evidenced by the solid-organ transplant literature. The weakened cellular immune system of HIV-infected patients resembles in some ways the iatrogenic immunosuppression in solid-organ transplant recipients. This article summarizes what is known about skin cancer in the solid-organ transplant population and compares the immunodysregulation of HIV infection with the iatrogenic immunosuppression following solid-organ transplantation.
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Affiliation(s)
- Kord S Honda
- Division of Dermatology, Box 356524, University of Washington School of Medicine, 1959 NE Pacific Street, Seattle, WA 98195, USA.
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O'Connor JK, Nedzi LA, Zakris EL. Prostate adenocarcinoma and human immunodeficiency virus: report of three cases and review of the literature. Clin Genitourin Cancer 2006; 5:85-8. [PMID: 16859585 DOI: 10.3816/cgc.2006.n.023] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
The objective of this study was to evaluate the acute tolerance to definitive external-beam radiation therapy (RT; EBRT) in patients with prostate adenocarcinoma and HIV and to review the published literature for this population. Three patients with prostate adenocarcinoma and HIV were treated with definitive RT. Medical records were reviewed for prostate cancer and HIV characteristics, RT details, and acute toxicity. A review of the published literature was performed for epidemiology, management, and outcome of these patients. All 3 patients had excellent acute tolerance to definitive EBRT and, with short follow-up, all had decreasing prostate-specific antigen levels. The published literature regarding patients with prostate adenocarcinoma and HIV is scarce but suggests that men with HIV might be at higher risk of developing prostate cancer. External-beam radiation therapy, brachytherapy, and surgery have all been used in the management of these patients. All 3 patients with prostate adenocarcinoma and HIV had an excellent acute tolerance to EBRT. Prostate cancer is expected to become an increasingly important health problem for men infected with HIV as their life expectancy lengthens.
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Affiliation(s)
- John K O'Connor
- Medical Center of Louisiana at New Orleans, Charity Hospital, Radiation Oncology, Tulane University School of Medicine New Orleans, LA 70112, USA.
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Oehler-Jänne C, Seifert B, Lütolf UM, Ciernik IF. Local tumor control and toxicity in HIV-associated anal carcinoma treated with radiotherapy in the era of antiretroviral therapy. Radiat Oncol 2006; 1:29. [PMID: 16916475 PMCID: PMC1570351 DOI: 10.1186/1748-717x-1-29] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2006] [Accepted: 08/18/2006] [Indexed: 11/10/2022] Open
Abstract
PURPOSE To investigate the outcome of HIV-seropositive patients under highly active antiretroviral treatment (HAART) with anal cancer treated with radiotherapy (RT) alone or in combination with standard chemotherapy (CT). PATIENTS AND METHODS Clinical outcome of 81 HIV-seronegative patients (1988-2003) and 10 consecutive HIV-seropositive patients under HAART (1997-2003) that were treated with 3-D conformal RT of 59.4 Gy and standard 5-fluorouracil and mitomycin-C were retrospectively analysed. 10 TNM-stage and age matched HIV-seronegative patients (1992-2003) were compared with the 10 HIV-seropositive patients. Pattern of care, local disease control (LC), overall survival (OS), cancer-specific survival (CSS), and toxicity were assessed. RESULTS RT with or without CT resulted in complete response in 100% of HIV-seropositive patients. LC was impaired compared to matched HIV-seronegative patients after a median follow-up of 44 months (p = 0.03). OS at 5 years was 70% in HIV-seropositive patients receiving HAART and 69% in the matched controls. Colostomy-free survival was 70% (HIV+) and 100% (matched HIV-) and 78% (all HIV-). No HIV-seropositive patient received an interstitial brachytherapy boost compared to 42% of all HIV-seronegative patients and adherence to chemotherapy seemed to be difficult in HIV-seropositive patients. Acute hematological toxicity reaching 50% was high in HIV-seropositive patients receiving MMC compared with 0% in matched HIV-seronegative patients (p = 0.05) or 12% in all HIV-seronegative patients. The rate of long-term side effects was low in HIV-seropositive patients. CONCLUSION Despite high response rates to organ preserving treatment with RT with or without CT, local tumor failure seems to be high in HIV-positive patients receiving HAART. HIV-seropositive patients are subject to treatment bias, being less likely treated with interstitial brachytherapy boost probably due to HIV-infection, and they are at risk to receive less chemotherapy.
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Affiliation(s)
| | - Burkhardt Seifert
- Department for Social- and Preventive Medicine, Biostatistics, University of Zurich, Zurich, Switzerland
| | - Urs M Lütolf
- Radiation Oncology, Zurich University Hospital, Switzerland
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Calkins A, Stehman FB, Bundy B, Benda JA, Mannel RS, Seago P, Cappuccini F, Alvarez RD, Monk BJ, Maiman M. Human immunodeficiency virus testing in patients with invasive cervical carcinoma: a prospective trial of the gynecologic oncology group. Int J Gynecol Cancer 2006; 16:660-3. [PMID: 16681743 DOI: 10.1111/j.1525-1438.2006.00395.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
To determine the frequency of positive human immunodeficiency virus (HIV) serostatus among North American women 50 years of age or younger with invasive cervical cancer and to define their tolerance to treatment. Consenting patients with newly diagnosed invasive cervical cancer, age 50 or younger were tested by enzyme-linked immunosorbent assay. The study design anticipated that approximately 3% of patients would be HIV positive. After the accrual of 913 eligible and evaluable patients, interim analysis revealed that only 9/913 ( approximately 1%) patients were HIV seropositive, indicating that it would not be feasible to achieve the study objective. The study was closed to further accrual. Between 1994 and 1997, the frequency of positive HIV serostatus among North American women with newly diagnosed cervical cancer was quite low. As a consequence, no evaluation of response to treatment or treatment tolerance can be made.
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Affiliation(s)
- A Calkins
- Radiation Oncology, St. Joseph's Hospital/Cancer Institute, Fred J. Woods Radiation Center, Tampa, Florida, USA
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Gervaz P, Allal AS, Roth A, Morel P. Chemotherapeutic options in the management of anal cancer. Expert Opin Pharmacother 2006; 5:2479-84. [PMID: 15571466 DOI: 10.1517/14656566.5.12.2479] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
During the past two decades, anal cancer has served as a paradigm for the successful application of chemoradiation to solid tumours; so far, it remains one of the few carcinomas of the gastrointestinal tract which are curable without the need for definitive surgery. Since the original contribution by Nigro in 1974, surprisingly few changes have been made to the standard of care in chemotherapy, which still consists of a combination of 5-fluorouracil and mitomycin C. However, many issues have yet to be clarified, such as the potential role of cisplatin as a substitute to mitomycin, as well as treatment-induced toxicity in HIV-positive patients. In this paper, the management of patients with anal cancer is presented, and new chemotherapeutic options are critically reviewed. Finally, the authors' opinion regarding currently unresolved issues in the treatment of these rare neoplasms is expressed.
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Affiliation(s)
- Pascal Gervaz
- Hôpital Cantonal Universitaire de Genève, Clinique de Chirurgie Viscérale, Switzerland.
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