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1
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Yan Naing CL, Gittens J, Fok M, Fowler H, Vimalachandran D, Clifford RE. Does endoscopic management have a role in chronic radiation proctopathy: A systematic review. Colorectal Dis 2025; 27:e70086. [PMID: 40200602 DOI: 10.1111/codi.70086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 01/28/2025] [Accepted: 03/05/2025] [Indexed: 04/10/2025]
Abstract
AIM Chronic radiation proctopathy (CRP) is a significant side-effect of radiotherapy, and poses a challenge in clinical management, necessitating effective and standardized therapeutic approaches. The aim of this review is to investigate the role of endoscopic interventions for CRP, focusing on argon plasma coagulation (APC) and formalin application. METHOD A literature search was undertaken for studies that investigated the clinical responses to endoscopic management in patients with CRP. A systematic review was performed in accordance with PRISMA guidelines, and a meta-analysis of proportions was conducted with a random-effects model. ROBINS-I and the Cochrane Collaboration's tool were used to assess risk of bias in cohort studies and randomized control trials, respectively. RESULTS A total of 82 studies met the inclusion criteria, including 11 randomized control trials, 20 systematic reviews, one cohort study and 50 case series. A robust 89% (95% CI 84%-92%, p < 0.01 and 95% CI 84%-93%, p = 0.03) pooled response rate was demonstrated for both APC and formalin therapies, respectively. Adverse effects were generally minimal. CONCLUSION Endoscopic therapies, particularly APC and formalin, exhibit commendable clinical response rates in the management of CRP. However, the lack of standardized treatment protocols highlights the need for larger prospective studies. Clear guidelines, informed by defined outcomes and quality-of-life assessments, are imperative for enhancing patient outcomes and minimizing the morbidity associated with CRP.
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Affiliation(s)
- Chyu Lai Yan Naing
- Aintree University Hospital, Liverpool University Hospitals Foundation Trust, Liverpool, UK
| | - Jayden Gittens
- Institute of Systems, Integrative and Molecular Biology, The University of Liverpool, Liverpool, UK
| | - Matthew Fok
- Royal Liverpool University Hospital, Liverpool University Hospitals Foundation Trust, Liverpool, UK
| | - Hayley Fowler
- Institute of Systems, Integrative and Molecular Biology, The University of Liverpool, Liverpool, UK
| | - Dale Vimalachandran
- Institute of Systems, Integrative and Molecular Biology, The University of Liverpool, Liverpool, UK
- The Countess of Chester Hospital, Chester, UK
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2
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Beas-Lozano EL, Contreras S, Donald-Jaramillo MAM, Frayde-Aguilar C, Carrillo-Vidales J, Jaime-Casas S, Martinez-Cannon BA. Current management of cervical cancer in women living with HIV. Crit Rev Oncol Hematol 2024; 204:104519. [PMID: 39322024 DOI: 10.1016/j.critrevonc.2024.104519] [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: 01/30/2024] [Revised: 08/20/2024] [Accepted: 09/16/2024] [Indexed: 09/27/2024] Open
Abstract
Cervical cancer is a significant global health issue, particularly in low- and middle-income countries. Women living with HIV (WLWH) are not only at higher risk of cervical cancer due to their increased susceptibility to high-risk human papillomavirus (HPV) infection and compromised immune status, but also higher mortality rates have been reported. Therefore, prevention, optimal screening, use of highly active antiretroviral therapy (HAART), and early access to treatment are of utmost importance in this population. While international guidelines for cervical cancer state no treatment differences should be made for WLWH, there is evidence that this population of patients represents a challenge in decision-making for medical oncologists, radiation oncologists, and surgical oncologists. This review summarizes the available evidence on the different treatment strategies for WLWH and invasive cervical cancer and highlights the need for special considerations in screening andprevention of cervical cancer in WLWH.
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Affiliation(s)
- Evelyn Lilian Beas-Lozano
- Hemato-Oncology Department, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico
| | - Sergio Contreras
- Hemato-Oncology Department, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico
| | | | - Citlali Frayde-Aguilar
- Hemato-Oncology Department, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico
| | - Javier Carrillo-Vidales
- Surgery Department, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico
| | - Salvador Jaime-Casas
- Hemato-Oncology Department, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico
| | - Bertha Alejandra Martinez-Cannon
- Hemato-Oncology Department, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico; Gynaecology Unit, The Royal Marsden NHS Foundation Trust & Institute of Cancer Research, London SW3 6JJ, UK.
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3
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Evin C, Quéro L, Le Malicot K, Blanchet-Deverly S, Evesque L, Buchalet C, Lemanski C, Hamed NB, Rivin Del Campo E, Bauwens L, Pommier P, Lièvre A, Gouriou C, Tougeron D, Macé V, Sergent G, Diaz O, Zucman D, Mornex F, Locher C, De la Rochefordière A, Vendrely V, Huguet F. Efficacy and Toxicity of (Chemo)Radiation Therapy in HIV+ Patients with Squamous Cell Anal Cancer, a Subgroup Analysis of the National Multicenter Cohort FFCD-ANABASE. Int J Radiat Oncol Biol Phys 2024; 120:708-719. [PMID: 38912999 DOI: 10.1016/j.ijrobp.2024.04.067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 03/30/2024] [Accepted: 04/21/2024] [Indexed: 06/25/2024]
Abstract
PURPOSE The influence of human immunodeficiency virus (HIV) infection on clinical outcomes in patients receiving (chemo)radiation therapy (RT) for squamous cell carcinoma of the anus (SCCA) is debated. The objective of this study was to compare efficacy and safety according to HIV status in patients with SCCA treated with C/RT. METHODS AND MATERIALS Between January 2015 and April 2020, 488 patients with a known HIV status (17.6% HIV+) were treated with radiation therapy for SCCA and included in the FFCD-ANABASE multicentric prospective cohort. Clinical outcomes including overall survival (OS), locoregional recurrence-free survival, colostomy-free survival, response rate at 4 to 6 months, cancer-specific survival, relapse-free survival, and severe acute and late toxicity were compared between HIV+ and HIV- patients. RESULTS The median follow-up was 35.8 months. HIV+ patients were younger (P < .01) and predominantly male (P < .01). Intensity modulated radiation therapy was performed in 80.7% of patients, and 80.9% received concurrent chemotherapy. A higher proportion of HIV+ patients received induction chemotherapy compared with HIV- patients. No statistically significant difference in overall treatment time or severe acute and late toxicities was found between HIV+ and HIV- patients. In univariate analyses, OS (HR = 2.1 [CI 95% 1.2;3.5], P = .007), locoregional recurrence-free survival (HR = 1.7 [1.1;2.7], P = .02), and colostomy-free survival (HR = 1.7 [1.1;2.6], P = .01) were significantly shorter in HIV+ patients than in HIV- patients. Response rate, cancer-specific survival, and relapse-free survival were not significantly different. The recurrence site was significantly different according to HIV status. In the multivariate analysis, prognostic factors for OS were a World Health Organization performance status of ≥1 for the whole population, as well as HIV+ status for the subgroup of women. CONCLUSIONS HIV+ patients treated with chemo-RT for SCCA have poorer clinical outcomes, especially women. No difference was found in toxicity according to HIV status with intensity modulated radiation therapy technique.
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Affiliation(s)
- Cecile Evin
- Hôpital Tenon, APHP, Radiation Oncology Department, Sorbonne University, Paris, France.
| | - Laurent Quéro
- Hôpital Saint-Louis, APHP, Radiation Oncology Department, Paris, France
| | - Karine Le Malicot
- Fédération Francophone de Cancérologie Digestive (FFCD), Biostatistics Department, EPICAD INSERM LNC-UMR 1231, Bourgogne Franche-Comté University, Dijon, France
| | | | - Ludovic Evesque
- Centre Antoine Lacassagne, Medical Oncology Department, Nice, France
| | - Chloé Buchalet
- Institut du Cancer de Montpellier, Radiation Oncology Department, Montpellier, France
| | - Claire Lemanski
- Institut du Cancer de Montpellier, Radiation Oncology Department, Montpellier, France
| | - Nabil Baba Hamed
- Groupe Hospitalier Paris Saint Joseph, Medical Oncology Department, Paris, France
| | | | | | - Pascal Pommier
- Centre Léon Bérard, Radiation Oncology Department, Lyon, France
| | - Astrid Lièvre
- CHU de Rennes, Gastroenterology Department, Rennes, France
| | - Claire Gouriou
- CHU de Rennes, Gastroenterology Department, Rennes, France
| | - David Tougeron
- CHU de Poitiers, Gastroenterology and Hepatology Department, Poitiers, France
| | - Vincent Macé
- CHD-Vendée, Gastroenterology Department, La Roche sur Yon, France
| | - Guillaume Sergent
- Institut de Cancérologie Paris Nord, Radiation Oncology Department, Paris, France
| | - Olivia Diaz
- Groupe Hospitalier Mutualiste de Grenoble, Radiation Oncology Department, Grenoble, France
| | - David Zucman
- Hôpital Foch, Réseau Ville-Hôpital, Val de Seine, Paris, France
| | - Françoise Mornex
- Centre Hospitalier Lyon Sud, Radiation Oncology Department, Lyon, France
| | - Christophe Locher
- Centre Hospitalier de Meaux, Hepato-gastroenterology Department, Meaux, France
| | | | | | - Florence Huguet
- Hôpital Tenon, APHP, Radiation Oncology Department, Sorbonne University, Paris, France
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4
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Anorectal pathology in the HIV population: a guide for radiologists. Abdom Radiol (NY) 2022; 47:1762-1774. [PMID: 35284963 DOI: 10.1007/s00261-022-03470-z] [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: 11/24/2021] [Revised: 02/20/2022] [Accepted: 02/21/2022] [Indexed: 11/01/2022]
Abstract
Patients with human immunodeficiency virus (HIV) can present with a wide range of different acute and chronic pathologies. Anorectal conditions are particularly common in this unique patient population, including pathologies, such as proctitis, anorectal abscess, anorectal fistula, and anal squamous cell carcinoma. The radiologist plays a critical role in the assessment of these common forms of anorectal disease, as these conditions can present with various findings on imaging assessment. Pelvic CT, MRI, and FDG-PET/CT are among the most common modalities used for assessment of anorectal disease in the HIV patient population. Knowledge of the fundamental clinical and imaging findings associated with these pathologies in HIV patients is critical for radiologists.
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5
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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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6
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Holliday EB, Morris VK, Johnson B, Eng C, Ludmir EB, Das P, Minsky BD, Taniguchi C, Smith GL, Koay EJ, Koong AC, Delclos ME, Skibber JM, Rodriguez-Bigas MA, You YN, Bednarski BK, Tillman MM, Chang GJ, Jennings K, Messick CA. Definitive Intensity-Modulated Chemoradiation for Anal Squamous Cell Carcinoma: Outcomes and Toxicity of 428 Patients Treated at a Single Institution. Oncologist 2022; 27:40-47. [PMID: 35305097 PMCID: PMC8842324 DOI: 10.1093/oncolo/oyab006] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Accepted: 11/16/2021] [Indexed: 11/13/2022] Open
Abstract
Abstract
Background
Although intensity-modulated radiation therapy (IMRT) is considered the standard of care for the treatment of squamous cell carcinoma of the anus (SCCA), few large series have reported oncologic outcomes and toxicities. In this retrospective report, we aim to describe outcomes and toxicities after IMRT-based chemoradiation (CRT) for the treatment of SCCA, evaluate the impact of dose escalation (>54 Gy), and compare concurrent fluoropyrimidine in combination with either mitomycin or with cisplatin as chemosensitizers.
Methods
Patients treated at The University of Texas MD Anderson Cancer Center between January 1, 2003 and December 31, 2018 with IMRT-based CRT were included. Median time to locoregional recurrence, time to colostomy, and overall survival were estimated using the Kaplan–Meier method.
Results
A total of 428 patients were included; median follow-up was 4.4 years. Three hundred and thirty-four patients (78.0%) were treated with concurrent cisplatin and fluoropyrimidine, and 160 (37.4%) with >54 Gy. Two- and 5-year freedom from locoregional failure, freedom from colostomy failure, and overall survival were 86.5% and 81.2%, respectively, 90.0% and 88.3%, respectively, and 93.6% and 85.8%, respectively. Neither dose escalation nor mitomycin-based concurrent chemotherapy resulted in improved outcomes. Mitomycin-based concurrent chemotherapy was associated with in approximately 2.5 times increased grade 3 or greater acute toxicity. Radiation dose >54 Gy was associated with approximately 2.6 times increased Grade 3 or greater chronic toxicity.
Conclusions
Our results suggest IMRT-based CRT with concurrent fluoropyrimidine and cisplatin is a safe and feasible option for patient with SCCA and may cause less acute toxicity. The role for radiation dose escalation is unclear and requires further study.
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Affiliation(s)
- Emma B Holliday
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Van K Morris
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Benny Johnson
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Cathy Eng
- Vanderbilt Ingram Cancer Center, Nashville, TN, USA
| | - Ethan B Ludmir
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Prajnan Das
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Bruce D Minsky
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Cullen Taniguchi
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Grace L Smith
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Eugene J Koay
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Albert C Koong
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Marc E Delclos
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - John M Skibber
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | | | - Y Nancy You
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | | | - Mathew M Tillman
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - George J Chang
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | | | - Craig A Messick
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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7
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De B, Ludmir EB, Messick CA, Cagley MC, Morris VK, Das P, Minsky BD, Taniguchi CM, Smith GL, Koay EJ, Koong AC, Mohan R, Holliday EB. Prognostic impact of lymphopenia and neutrophil-lymphocyte ratio for patients with anal squamous cell carcinoma. J Gastrointest Oncol 2021; 12:2412-2422. [PMID: 34790402 DOI: 10.21037/jgo-21-323] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 08/23/2021] [Indexed: 12/31/2022] Open
Abstract
Background Outcomes after definitive chemoradiation for squamous cell carcinoma are generally favorable. However, biomarkers to further yield prognostic information are desired. Treatment-related lymphopenia as well as an elevated baseline neutrophil-lymphocyte ratio have been associated with worse survival in several cancer types. We evaluated absolute lymphocyte count and neutrophil-lymphocyte ratio at baseline and at treatment-related nadir in patients with anal cancer for associations with oncologic endpoints. Methods We conducted a retrospective analysis of 428 consecutive patients with non-metastatic anal cancer treated with definitive, intensity-modulated radiation therapy-based chemoradiation. We analyzed absolute neutrophil and lymphocyte counts at several timepoints: pretreatment, weekly during treatment, and in the six weeks following treatment completion. Neutrophil-lymphocyte ratio was calculated at baseline and treatment-related nadir. We estimated oncologic endpoints using life tables and compared them using the log-rank test. We conducted univariate and multivariable time-to-event analyses using Cox proportional hazards. Results Median absolute lymphocyte count at baseline and nadir were 1.80 [interquartile range (IQR), 1.45-2.32] k/µL and 0.26 (IQR, 0.18-0.36) k/µL, respectively, and 31% developed treatment-related grade 4 lymphopenia. Median neutrophil-lymphocyte ratio at baseline and nadir were 2.34 (IQR, 1.68-3.30) and 8.80 (IQR, 5.86-12.68), respectively. Estimates of overall survival, local failure-free survival, distant metastasis-free survival (DMFS), and freedom from colostomy at 5 years were 87%, 86%, 82%, and 88%, respectively. Baseline and nadir absolute lymphocyte count were not associated with selected outcomes on univariate analysis. On multivariable analysis, factors independently associated with death included T3-T4 disease, HIV-positive status, treatment break, and baseline neutrophil-lymphocyte ratio >3. Baseline neutrophil-lymphocyte ratio showed a trend toward association with distant progression or death (P=0.07). The 5-year overall survival estimates for patients with baseline neutrophil-lymphocyte ratios ≤3 and >3 were 92.3% and 80.6%, respectively. Conclusions Lymphopenia during and after chemoradiation for anal cancer is common but does not appear to be associated with worse survival, recurrence, or metastases. However, elevated baseline neutrophil-lymphocyte ratio was independently associated with overall survival, local recurrence-free survival, and DMFS. Further studies are needed to determine the clinical utility of baseline neutrophil-lymphocyte ratio to guide treatment and follow-up.
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Affiliation(s)
- Brian De
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ethan B Ludmir
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Craig A Messick
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Matthew C Cagley
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Van K Morris
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Prajnan Das
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Bruce D Minsky
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Cullen M Taniguchi
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Grace L Smith
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Eugene J Koay
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Albert C Koong
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Radhe Mohan
- Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Emma B Holliday
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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8
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Dahiya DS, Kichloo A, Tuma F, Albosta M, Wani F. Radiation Proctitis and Management Strategies. Clin Endosc 2021; 55:22-32. [PMID: 34788934 PMCID: PMC8831406 DOI: 10.5946/ce.2020.288] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Accepted: 01/30/2021] [Indexed: 11/24/2022] Open
Abstract
Radiotherapy (RT) is a treatment modality that uses high-energy rays or radioactive agents to generate ionizing radiation against rapidly dividing cells. The main objective of using radiation in cancer therapy is to impair or halt the division of the tumor cells. Over the past few decades, advancements in technology, the introduction of newer methods of RT, and a better understanding of the pathophysiology of cancers have enabled physicians to deliver doses of radiation that match the exact dimensions of the tumor for greater efficacy, with minimal exposure of the surrounding tissues. However, RT has numerous complications, the most common being radiation proctitis (RP). It is characterized by damage to the rectal epithelium by secondary ionizing radiation. Based on the onset of signs and symptoms, post-radiotherapy RP can be classified as acute or chronic, each with varying levels of severity and complication rates. The treatment options available for RP are limited, with most of the data on treatment available from case reports or small studies. Here, we describe the types of RT used in modern-day medicine and radiation-mediated tissue injury. We have primarily focused on the classification, epidemiology, pathogenesis, clinical features, treatment strategies, complications, and prognosis of RP.
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Affiliation(s)
| | - Asim Kichloo
- Department of Internal Medicine, Central Michigan University, Saginaw, MI, USA.,Department of Internal Medicine, Samaritan Medical Center, Watertown, NY, USA
| | - Faiz Tuma
- Department of Surgery, Central Michigan University, Saginaw, MI, USA
| | - Michael Albosta
- Department of Internal Medicine, Central Michigan University, Saginaw, MI, USA
| | - Farah Wani
- Department of Family Medicine, Samaritan Medical Center, Watertown, NY, USA
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9
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Abstract
Anal cancer, despite being a rare malignancy, is increasing in incidence, accounting for 0.5% of all new cancer cases in the United States, with rate of new cases being 1.9 per 100,000 men and women. It is common in immunocompromised individuals, especially those with malignancy, human immunodeficiency virus (HIV) and human papillomavirus (HPV) infection. Despite similar treatment of anal cancer in both HIV-positive and negative patients, guidelines for prevention and treatment of therapy-related side effects are rarely studied. While these patients have a better prognosis on HAART, limited guidelines exist regarding appropriate therapy. There is a common link between HPV and HIV and the transmission of one is associated with increased risk of transmission of the other. HPV vaccine which is known to prevent high-grade cervical intraepithelial neoplasia is thought to also decrease the incidence of anal intraepithelial neoplasia. The association of HPV vaccine in the prevention of anal cancer in high-risk groups with HIV is a scarcely studied subject that requires further research.
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Affiliation(s)
| | - Sachi Singhal
- Internal Medicine, Crozer Keystone Health System, Upland, USA
| | - Devashish Desai
- Internal Medicine, Crozer Keystone Health System, Upland, USA
| | - Meghana Parsi
- Internal Medicine, Crozer Keystone Heath System, Upland, USA
| | - Rashmika Potdar
- Hematology and Medical Oncology, Crozer Keystone Health System, Upland, USA
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10
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Camandaroba MPG, Iseas S, Oliveira C, Taboada RG, Xerfan MP, Mauro CC, Silva VS, Barros M, de Jesus VHF, Felismino T, Aguiar S, Gobo ML, Mello CA, Riechelmann RP. Disease-Free Survival and Time to Complete Response After Definitive Chemoradiotherapy for Squamous-Cell Carcinoma of the Anus According to HIV Infection. Clin Colorectal Cancer 2020; 19:e129-e136. [DOI: 10.1016/j.clcc.2020.03.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2019] [Revised: 03/18/2020] [Accepted: 03/22/2020] [Indexed: 12/18/2022]
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11
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Pan M. Case of Complete Remission After Volumetric Modulated Arc Therapy to Primary Tumor Alone in Locally Advanced Anal Canal Cancer With Active AIDS and Low CD4 Cell Count: Longest Survival in History? Cureus 2020; 12:e9093. [PMID: 32789041 PMCID: PMC7417064 DOI: 10.7759/cureus.9093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
The incidence of anal canal cancer (AC) is increased in HIV-positive individuals and is often associated with poor prognosis. High viral load and low CD4 cell count have long been considered relative contraindications for combined modality treatment (CMT) with concurrent chemotherapy and external beam radiation treatment (EBRT) for AC due to severe toxicities. EBRT alone is quite often considered as palliative treatment in nature. We report a case of complete remission (CR) of locally advanced anal canal squamous cell carcinoma (ACSCC) cured after volumetric modulated arc therapy (VMAT) to the primary tumor alone in a 62-year-old male with a 30-year history of AIDS, characterized by an HIV viral load over one million and low CD4 cell count around 100 mm-3. VMAT achieved excellent long-term local control of AC and good quality of life (QoL) of the patient without severe toxicity that requires diverting colostomy.
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Affiliation(s)
- Ming Pan
- Radiation Oncology, Windsor Regional Hospital Cancer Program, Windsor, CAN
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12
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Calkins KL, Chander G, Joshu CE, Visvanathan K, Fojo AT, Lesko CR, Moore RD, Lau B. Immune Status and Associated Mortality After Cancer Treatment Among Individuals With HIV in the Antiretroviral Therapy Era. JAMA Oncol 2020; 6:227-235. [PMID: 31804663 PMCID: PMC6902188 DOI: 10.1001/jamaoncol.2019.4648] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Accepted: 08/12/2019] [Indexed: 12/12/2022]
Abstract
Importance Immunologic decline associated with cancer treatment in people with HIV is not well characterized. Quantifying excess mortality associated with cancer treatment-related immunosuppression may help inform cancer treatment guidelines for persons with HIV. Objective To estimate the association between cancer treatment and CD4 count and HIV RNA level in persons with HIV and between posttreatment CD4 count and HIV RNA trajectories and all-cause mortality. Design, Setting, and Participants This observational cohort study included 196 adults with HIV who had an incident first cancer and available cancer treatment data while in the care of The Johns Hopkins HIV Clinic from January 1, 1997, through March 1, 2016. The study hypothesized that chemotherapy and/or radiotherapy in people with HIV would increase HIV RNA levels owing to treatment tolerability issues and would be associated with a larger initial decline in CD4 count and slower CD4 recovery compared with surgery or other treatment. An additional hypothesis was that these CD4 count declines would be associated with higher mortality independent of baseline CD4 count, antiretroviral therapy use, and risk due to the underlying cancer. Data were analyzed from December 1, 2017, through April 1, 2018. Exposures Initial cancer treatment category (chemotherapy and/or radiotherapy vs surgery or other treatment). Main Outcomes and Measures Post-cancer treatment longitudinal CD4 count, longitudinal HIV RNA level, and all-cause mortality. Results Among the 196 participants (135 [68.9%] male; median age, 50 [interquartile range, 43-55] years), chemotherapy and/or radiotherapy decreased initial CD4 count by 203 cells/μL (95% CI, 92-306 cells/μL) among those with a baseline CD4 count of greater than 500 cells/μL. The decline for those with a baseline CD4 count of no greater than 350 cells/μL was 45 cells/μL (interaction estimate, 158 cells/μL; 95% CI, 31-276 cells/μL). Chemotherapy and/or radiotherapy had no detrimental association with HIV RNA levels. After initial cancer treatment, every 100 cells/μL decrease in CD4 count resulted in a 27% increase in mortality (hazard ratio, 1.27; 95% CI, 1.08-1.53), adjusting for HIV RNA level. No significant increase in mortality was associated with a unit increase in log10 HIV RNA after adjusting for CD4 count (hazard ratio, 1.24; 95% CI, 0.94-1.65). Conclusions and Relevance In this study, chemotherapy and/or radiotherapy was associated with significantly reduced initial CD4 count in adults with HIV compared with surgery or other treatment. Lower CD4 count after cancer treatment was associated with an increased hazard of mortality. Further research is necessary on the immunosuppressive effects of cancer treatment in adults with HIV and whether health care professionals must consider the balance of cancer treatment efficacy against the potential cost of further immunosuppression. Monitoring of immune status may also be helpful given the decrease in CD4 count after treatment and the already immunocompromised state of patients with HIV.
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Affiliation(s)
- Keri L. Calkins
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Geetanjali Chander
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
- School of Medicine, Department of Medicine, The Johns Hopkins University, Baltimore, Maryland
| | - Corinne E. Joshu
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Kala Visvanathan
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
- School of Medicine, Department of Medical Oncology, The Johns Hopkins University, Baltimore, Maryland
| | - Anthony T. Fojo
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
- School of Medicine, Department of Medicine, The Johns Hopkins University, Baltimore, Maryland
| | - Catherine R. Lesko
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Richard D. Moore
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
- School of Medicine, Department of Medicine, The Johns Hopkins University, Baltimore, Maryland
| | - Bryan Lau
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
- School of Medicine, Department of Medicine, The Johns Hopkins University, Baltimore, Maryland
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13
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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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14
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Grover S, MacDuffie EC, Wang Q, Bvochora-Nsingo M, Bhatia RK, Balang D, Chiyapo SP, Luckett R, Ramogola-Masire D, Dryden-Peterson SL, Lin LL, Shin SS, Zetola NM. HIV infection is not associated with the initiation of curative treatment in women with cervical cancer in Botswana. Cancer 2019; 125:1645-1653. [PMID: 30801696 DOI: 10.1002/cncr.31972] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Revised: 10/29/2018] [Accepted: 11/09/2018] [Indexed: 12/24/2022]
Abstract
BACKGROUND Cervical cancer is the leading cause of cancer death in Sub-Saharan Africa. The risk of developing cancer is increased for women living with human immunodeficiency virus (HIV) infection. It is unknown which factors predict the initiation of curative chemoradiotherapy (CRT) in resource-limited settings and whether HIV is associated with initiating curative CRT in settings with a high HIV burden. METHODS All women living with and without HIV infection who were initiating curative and noncurative CRT for locally advanced cervical cancer in Botswana were prospectively enrolled in an observational study. The factors associated with receiving CRT were evaluated in all patients and the subgroup of women living with HIV. RESULTS Of 519 enrolled women, 284 (55%) initiated CRT with curative intent. The curative cohort included 200 women (70.4%) who were living with HIV and had a median CD4 count of 484.0 cells/μL (interquartile range, 342.0-611.0 cells/μL). In the noncurative cohort, 157 of 235 women (66.8%) were living with HIV and had a median CD4 count of 476.5 cells/μL (interquartile range, 308.0-649.5 cells/μL). HIV status was not associated with initiating curative CRT (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.58-1.56). The factors associated with receiving curative CRT treatment on multivariable analysis in all patients included baseline hemoglobin levels ≥10 g/dL (OR, 1.80; 95% CI, 1.18-2.74) and stage I or II versus stage III or IV disease (OR, 3.16; 95% CI, 2.10-4.75). Women aged >61 years were less likely to receive curative treatment (OR, 0.43; 95% CI, 0.24-0.75). Among women who were living with HIV, higher CD4 cell counts were associated with higher rates of CRT initiation. CONCLUSIONS The initiation of CRT with curative intent does not depend on HIV status. Significant predictors of CRT initiation include baseline hemoglobin level, disease stage, and age.
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Affiliation(s)
- Surbhi Grover
- Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.,Botswana-University of Pennsylvania Partnership, Gaborone, Botswana.,Princess Marina Hospital, Gaborone, Botswana.,School of Medicine, University of Botswana, Gaborone, Botswana
| | - Emily C MacDuffie
- Warren Alpert Medical School of Brown University, Providence, Rhode Island
| | - Qiao Wang
- Sue and Bill Gross School of Nursing, University of California, Irvine, Irvine, California
| | | | - Rohini K Bhatia
- University of Rochester, School of Medicine and Dentistry, Rochester, New York
| | - Dawn Balang
- Department of Oncology, Gaborone Private Hospital, Gaborone, Botswana
| | | | - Rebecca Luckett
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.,Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Doreen Ramogola-Masire
- School of Medicine, University of Botswana, Gaborone, Botswana.,Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Scott L Dryden-Peterson
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.,Department of Medicine, Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts.,Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Lilie L Lin
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Sanghyuk S Shin
- Sue and Bill Gross School of Nursing, University of California, Irvine, Irvine, California
| | - Nicola M Zetola
- Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.,Botswana-University of Pennsylvania Partnership, Gaborone, Botswana
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15
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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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16
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Cook M, Baker K, Redman M, Lachance K, Nguyen MH, Parvathaneni U, Bhatia S, Nghiem P, Tseng YD. Differential Outcomes Among Immunosuppressed Patients With Merkel Cell Carcinoma: Impact of Immunosuppression Type on Cancer-specific and Overall Survival. Am J Clin Oncol 2019; 42:82-88. [PMID: 30211723 PMCID: PMC8666386 DOI: 10.1097/coc.0000000000000482] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVES Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer with higher incidence among whites, elderly, and immunosuppressed patients. Although immunosuppressed MCC patients are at higher risk of recurrence and MCC-related death, it is unknown whether immunosuppression type is associated with differential outcomes. MATERIALS AND METHODS We retrospectively evaluated 89 nonmetastatic MCC patients with a diagnosis of chronic immunosuppression. Immunosuppression was categorized as chronic lymphocytic leukemia (31% of cohort), other hematologic malignancies (18%), solid organ transplant (21%), autoimmune disease (21%), and human immunodeficiency virus acquired deficiency syndrome (8%). Progression-free survival (PFS) and MCC-specific survival (MSS) were estimated with the cumulative incidence function. Overall survival (OS) was estimated by the Kaplan-Meier method. RESULTS With a median follow-up of 52 months, 53 deaths occurred (42 from MCC, 7 unknown, and 4 non-MCC). Two-year PFS, MSS, and OS were 30%, 55%, and 52%, respectively. Human immunodeficiency virus/acquired deficiency syndrome and solid organ transplant patients were diagnosed with MCC at a younger age (median 55 and 59 y, respectively) and with more advanced stage disease compared with other immunosuppressed subgroups. PFS did not significantly differ among the 5 immunosuppression subgroups (P=0.30), but significant differences were observed in MSS and OS (both P=0.01). Controlling for potential confounders for OS, including age and stage, immunosuppression type was still significantly associated with risk of death (P=0.01). CONCLUSIONS Among immunosuppressed MCC patients, recurrent MCC is the major cause of mortality. The risk of death from MCC differs among immunosuppression types, suggesting important biological differences in host-tumor immune interactions.
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Affiliation(s)
| | - Kelsey Baker
- Clinical Research Division, Fred Hutchinson Cancer Research Center
| | - Mary Redman
- Clinical Research Division, Fred Hutchinson Cancer Research Center
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17
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Quéro L, Gobert A, Spano JP. [Radiotherapy for HIV-infected patients]. Cancer Radiother 2018; 22:496-501. [PMID: 30087055 DOI: 10.1016/j.canrad.2018.06.007] [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: 06/27/2018] [Accepted: 06/29/2018] [Indexed: 11/28/2022]
Abstract
Since the advent of highly active antiretroviral therapy, cancer incidence is still 2 to 3-fold higher in patients infected by human immunodeficiency virus (HIV) than in the general population, with an increased incidence of malignancies not associated with acquired immunodeficiency syndrome (AIDS). HIV-infected patients cancer treatment does not differ from that in the general population. However, the management of those patients have some particularities due to preexisting comorbid conditions, including metabolic, cardiovascular, renal or hepatic complications and the risk for potential drug - drug interactions in HIV-infected patients. In this review, we described efficacy and tolerance of radiotherapy with or without chemotherapy in this frail population treated for cancer. Utilization of modern radiotherapy techniques such as intensity-modulated radiotherapy may improve the treatment tolerance.
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Affiliation(s)
- L Quéro
- Service de cancérologie-radiothérapie, hôpital Saint-Louis, 1, avenue Claude-Vellefaux, 75010 Paris, France.
| | - A Gobert
- Groupe hospitalier Pitié-Salpêtrière-Charles-Foix, 75013 Paris, France; Sorbonne Université, 75006 Paris, France
| | - J-P Spano
- Groupe hospitalier Pitié-Salpêtrière-Charles-Foix, 75013 Paris, France; Sorbonne Université, 75006 Paris, France
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18
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Kim S, François E, André T, Samalin E, Jary M, El Hajbi F, Baba-Hamed N, Pernot S, Kaminsky MC, Bouché O, Desrame J, Zoubir M, Ghiringhelli F, Parzy A, De La Fouchardiere C, Smith D, Deberne M, Spehner L, Badet N, Adotevi O, Anota A, Meurisse A, Vernerey D, Taieb J, Vendrely V, Buecher B, Borg C. Docetaxel, cisplatin, and fluorouracil chemotherapy for metastatic or unresectable locally recurrent anal squamous cell carcinoma (Epitopes-HPV02): a multicentre, single-arm, phase 2 study. Lancet Oncol 2018; 19:1094-1106. [PMID: 30042063 DOI: 10.1016/s1470-2045(18)30321-8] [Citation(s) in RCA: 96] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2018] [Revised: 04/13/2018] [Accepted: 04/18/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND The incidence of anal squamous cell carcinoma has been increasing markedly in the past few decades. Currently, there is no validated treatment for advanced-stage anal squamous cell carcinoma. Therefore, we aimed to validate the clinical activity and safety of docetaxel, cisplatin, and fluorouracil (DCF) chemotherapy in patients with metastatic or unresectable locally recurrent anal squamous cell carcinoma. METHODS We did a multicentre, single-arm, phase 2 study. We recruited patients from 25 academic hospitals, cancer research centres, and community hospitals in France who were aged 18 years or older with histologically confirmed anal squamous cell carcinoma, with metastatic disease or with unresectable local recurrence; an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; and with at least one evaluable lesion according to the Response Evaluation Criteria in Solid Tumors (version 1.1). Chemotherapy-naive patients received either six cycles of standard DCF (75 mg/m2 docetaxel and 75 mg/m2 cisplatin on day 1 and 750 mg/m2 per day of fluorouracil for 5 days, every 3 weeks) or eight cycles of modified DCF (40 mg/m2 docetaxel and 40 mg/m2 cisplatin on day 1 and 1200 mg/m2 per day of fluorouracil for 2 days, every 2 weeks), which were administered intravenously. The choice between the standard versus modified regimens was recommended based on, but not limited to, age (≤75 years vs >75 years) and ECOG performance status (0 vs 1). The primary endpoint was investigator-assessed progression-free survival at 12 months from the first DCF cycle; for the primary endpoint to be met, at least 11 (17%) of 66 enrolled patients had to be alive without disease progression at 12 months. Efficacy and safety analyses were done in a modified intention-to-treat population, defined as all patients who were evaluable for progression at 12 months who received at least one cycle of DCF. This trial is registered at ClinicalTrials.gov, number NCT02402842, and the final results are presented here. FINDINGS Between Sept 17, 2014, and Dec 7, 2016, we enrolled 69 patients. Of these patients, three did not receive DCF. Of the 66 patients who received treatment, 36 received the standard DCF regimen and 30 received modified DCF. The primary endpoint was met: 31 (47%) of 66 patients were alive and progression free at 12 months. 22 (61%) of 36 patients who received the standard DCF regimen and 18 (60%) of 30 patients who received the modified DCF regimen had disease progression at data cutoff. 46 (70%) of 66 patients had at least one grade 3-4 adverse event (30 [83%] of 36 in the standard DCF regimen and 16 [53%] of 30 in the modified DCF regimen). The most common grade 3-4 adverse events were neutropenia (15 [23%]; eight [22%] for standard DCF vs seven [23%] for modified DCF), diarrhoea (12 [18%]; nine [25%] vs three [10%]), asthenia (ten [15%]; eight [22%] vs two [7%]), anaemia (ten [15%]; six [17%] vs four [13%]), lymphopenia (eight [12%]; three [8%] vs five [17%]), mucositis (seven [11%]; seven [19%] vs none), and vomiting (seven [11%]; five [14%] vs two [7%]). No grade 4 non-haematological adverse events and febrile neutropenia were observed with modified DCF, whereas three (8%) grade 4 non-haematological adverse events and five (14%) cases of febrile neutropenia were reported with standard DCF. 97 serious adverse events were reported (69 in patients who received the standard DCF regimen [61 drug-related] and 28 in those given the modified DCF regimen [14 drug-related]). No treatment-related deaths were recorded. INTERPRETATION Compared with standard DCF, modified DCF provided long-lasting response with good tolerability in patients with metastatic or unresectable locally recurrent anal squamous cell carcinoma with ECOG performance status of 0-1 in the first-line setting, and therefore could be considered as a new standard of care for these patients. Regarding the elevated risk of high-grade and serious adverse events and febrile neutropenia, standard DCF cannot be recommended in this situation. FUNDING Besançon University Hospital and Ligue contre le cancer Grand-Est.
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Affiliation(s)
- Stefano Kim
- Department of Oncology, University Hospital of Besancon, Centre Hospitalier Universitaire de Besançon, Besançon, France; Department of Oncology and Radiotherapy, Hôpital Nord Franche Comté, Montbéliard, France; Clinical Investigational Center, CIC-1431, University Hospital of Besançon, Besançon, France; INSERM, Unit 1098, University of Bourgogne Franche-Comté, Besançon, France; Groupe Coopérateur Multidisciplinaire en Oncologie (GERCOR) Oncology Multidisciplinary Group, Paris, France; Fédération Francophone de Cancérologie Digestive (FFCD), Dijon, France.
| | - Eric François
- Medical Oncology Department, Centre Antoine-Lacassagne, Nice, France
| | - Thierry André
- Groupe Coopérateur Multidisciplinaire en Oncologie (GERCOR) Oncology Multidisciplinary Group, Paris, France; Department of Medical Oncology, Hôpital Saint Antoine, Assistance Publique Hôpitaux de Paris and Sorbonne Universités, Paris, France
| | - Emmanuelle Samalin
- Department of Oncology, Institut du Cancer de Montpellier, Montpellier, France
| | - Marine Jary
- Department of Oncology, University Hospital of Besancon, Centre Hospitalier Universitaire de Besançon, Besançon, France; Department of Oncology and Radiotherapy, Hôpital Nord Franche Comté, Montbéliard, France; Clinical Investigational Center, CIC-1431, University Hospital of Besançon, Besançon, France; INSERM, Unit 1098, University of Bourgogne Franche-Comté, Besançon, France; Groupe Coopérateur Multidisciplinaire en Oncologie (GERCOR) Oncology Multidisciplinary Group, Paris, France
| | - Farid El Hajbi
- Department of Oncology, Centre Oscar Lambret, Lille, France
| | - Nabil Baba-Hamed
- Department of Oncology, Groupe Hospitalier Paris Saint-Joseph, Paris, France
| | - Simon Pernot
- Department of Oncology, Hôpital Européen Georges-Pompidou, Paris, France
| | | | - Olivier Bouché
- Fédération Francophone de Cancérologie Digestive (FFCD), Dijon, France; Department of Oncology, Centre Hospitalier Universitaire de Reims, Reims, France
| | - Jérôme Desrame
- Department of Oncology, Hôpital Privé Jean Mermoz, Lyon, France
| | - Mustapha Zoubir
- Department of Oncology, Hôpital Privé des Peupliers, Paris, France
| | | | - Aurélie Parzy
- Department of Oncology, Centre François Baclesse, Caen, France
| | | | - Denis Smith
- Department of Oncology, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
| | - Mélanie Deberne
- Department of Oncology, Centre Hospitalier Lyon Sud, Lyon, France
| | - Laurie Spehner
- INSERM, Unit 1098, University of Bourgogne Franche-Comté, Besançon, France
| | - Nicolas Badet
- Department of Oncology, Clinique Saint Vincent, Besançon, France
| | - Olivier Adotevi
- Department of Oncology, University Hospital of Besancon, Centre Hospitalier Universitaire de Besançon, Besançon, France; INSERM, Unit 1098, University of Bourgogne Franche-Comté, Besançon, France
| | - Amélie Anota
- Methodology and Quality of Life in Oncology Unit, University Hospital of Besançon, Besançon, France; INSERM, Unit 1098, University of Bourgogne Franche-Comté, Besançon, France; French National Platform Quality of Life and Cancer, Besançon, France
| | - Aurélia Meurisse
- Methodology and Quality of Life in Oncology Unit, University Hospital of Besançon, Besançon, France
| | - Dewi Vernerey
- Methodology and Quality of Life in Oncology Unit, University Hospital of Besançon, Besançon, France; INSERM, Unit 1098, University of Bourgogne Franche-Comté, Besançon, France; Groupe Coopérateur Multidisciplinaire en Oncologie (GERCOR) Oncology Multidisciplinary Group, Paris, France
| | - Julien Taieb
- Department of Oncology, Hôpital Européen Georges-Pompidou, Paris, France
| | - Véronique Vendrely
- Fédération Francophone de Cancérologie Digestive (FFCD), Dijon, France; Department of Oncology, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
| | - Bruno Buecher
- Fédération Francophone de Cancérologie Digestive (FFCD), Dijon, France; Department of Oncology, Institut Curie, Paris, France
| | - Christophe Borg
- Department of Oncology, University Hospital of Besancon, Centre Hospitalier Universitaire de Besançon, Besançon, France; Department of Oncology and Radiotherapy, Hôpital Nord Franche Comté, Montbéliard, France; Clinical Investigational Center, CIC-1431, University Hospital of Besançon, Besançon, France; INSERM, Unit 1098, University of Bourgogne Franche-Comté, Besançon, France; Groupe Coopérateur Multidisciplinaire en Oncologie (GERCOR) Oncology Multidisciplinary Group, Paris, France; Fédération Francophone de Cancérologie Digestive (FFCD), Dijon, France
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19
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The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for Anal Squamous Cell Cancers (Revised 2018). Dis Colon Rectum 2018; 61:755-774. [PMID: 29878949 DOI: 10.1097/dcr.0000000000001114] [Citation(s) in RCA: 124] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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20
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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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21
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Pappou EP, Magruder JT, Fu T, Hicks CW, Herman JM, Fang S, Wick EC, Safar B, Gearhart SL, Efron JE. Prognostic and Predictive Clinicopathologic Factors of Squamous Anal Canal Cancer in HIV-Positive and HIV-Negative Patients: Does HAART Influence Outcomes? World J Surg 2018; 42:876-883. [PMID: 28948325 PMCID: PMC6198800 DOI: 10.1007/s00268-017-4201-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND The incidence of squamous cell carcinoma (SCC) of the anal canal has been rising over the past decades, especially in patients infected with human immunodeficiency virus (HIV). Despite the advent of potent multidrug regimens to treat HIV-termed highly active antiretroviral therapy (HAART), anal SCC rates have not declined, and the impact of HAART on anal SCC remains controversial. AIM The purpose of this study was to define outcomes of anal SCC treatment in HIV-positive and HIV-negative patients. METHODS AND MATERIALS A retrospective single-institution analysis was performed on all patients with anal SCC treated at the Johns Hopkins Hospital between 1991 and 2010. The primary outcomes measured were 5-year overall survival (5-year OS), median survival, and relapse rates. RESULTS Our search identified 93 patients with anal SCC. Patients had a mean age of 54 years; 37.6% were male, and 21.5% were HIV-positive. Median follow-up was 28 months. Relapse occurred in 16.1% of patients. Median time to relapse was 20 months. Relapse rates were slightly higher with HIV-positive versus negative patients (30.0 vs. 12.3%) but did not reach statistical significance (p = 0.06). Among HIV-positive patients, those who relapsed were more likely to be on HAART than those who did not relapse (83.3 vs. 14.3%, p = 0.007). 5-year OS was 58.9% for the total group of patients with no significant difference between those who relapsed versus those who did not (76.2 vs. 54.5%, p = 0.20). No survival difference was seen between HIV-positive and negative patients. Survival was associated with AJCC stage in all patients. CONCLUSION In our small series, HIV infection was not associated with a significantly higher relapse rate or worse 5-year OS among patients with anal SCC. HAART was associated with a higher rate of relapse in HIV-positive patients. AJCC staging predicted survival in both relapsed and non-relapsed patients regardless of HIV status.
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Affiliation(s)
- Emmanouil P Pappou
- Division of Colon and Rectal Surgery, Interim Director, Department of Surgery, The Johns Hopkins Hospital, 720 Rutland Avenue - Ross 759, Baltimore, MD, 21205, USA
- Department of Colorectal Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Jonathan T Magruder
- Division of Colon and Rectal Surgery, Interim Director, Department of Surgery, The Johns Hopkins Hospital, 720 Rutland Avenue - Ross 759, Baltimore, MD, 21205, USA
| | - Tao Fu
- Department of Gastrointestinal Surgery, Daping Hospital, Third Military Medical University, Chongqing, China
| | - Caitlin W Hicks
- Division of Colon and Rectal Surgery, Interim Director, Department of Surgery, The Johns Hopkins Hospital, 720 Rutland Avenue - Ross 759, Baltimore, MD, 21205, USA
| | - Joseph M Herman
- Department of Radiation Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
- Department of Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA
| | - Sandy Fang
- Division of Colon and Rectal Surgery, Interim Director, Department of Surgery, The Johns Hopkins Hospital, 720 Rutland Avenue - Ross 759, Baltimore, MD, 21205, USA
| | - Elizabeth C Wick
- Division of Colon and Rectal Surgery, Interim Director, Department of Surgery, The Johns Hopkins Hospital, 720 Rutland Avenue - Ross 759, Baltimore, MD, 21205, USA
| | - Bashar Safar
- Division of Colon and Rectal Surgery, Interim Director, Department of Surgery, The Johns Hopkins Hospital, 720 Rutland Avenue - Ross 759, Baltimore, MD, 21205, USA
| | - Susan L Gearhart
- Division of Colon and Rectal Surgery, Interim Director, Department of Surgery, The Johns Hopkins Hospital, 720 Rutland Avenue - Ross 759, Baltimore, MD, 21205, USA
| | - Jonathan E Efron
- Division of Colon and Rectal Surgery, Interim Director, Department of Surgery, The Johns Hopkins Hospital, 720 Rutland Avenue - Ross 759, Baltimore, MD, 21205, USA.
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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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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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Moureau-Zabotto L, Vendrely V, Abramowitz L, Borg C, Francois E, Goere D, Huguet F, Peiffert D, Siproudhis L, Ducreux M, Bouché O. Anal cancer: French Intergroup Clinical Practice Guidelines for diagnosis, treatment and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, SNFCP). Dig Liver Dis 2017; 49:831-840. [PMID: 28610905 DOI: 10.1016/j.dld.2017.05.011] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2017] [Revised: 04/13/2017] [Accepted: 05/12/2017] [Indexed: 12/11/2022]
Abstract
INTRODUCTION This document is a summary of the French Intergroup guidelines regarding the management of anal carcinomas, published in November 2016. METHODS It is a collaborative work produced under the auspices of the majority of the French medical societies involved in the management of anal cancer. It is based on the previous guidelines published in 2010. Recommendations are graded in three categories, according to the amount of evidence found in the literature. RESULTS Non-metastatic anal carcinomas can be divided into two risk groups, according to magnetic resonance imaging (MRI) or endorectal-ultrasonograpy. Localized small cancers (T1N0) are mainly treated by exclusive radiation therapy in the case of cancers of the anal canal, or by surgery in the case of cancers of the anal margin. The recommended treatment of locally advanced tumours (T2-T4, N0-N2) is definitive concomitant radio-chemotherapy. Salvage surgery should be reserved for patients with poor response, tumour progression or local relapse after radio-chemotherapy, or in cases of persistent vaginal fistula or total anal incontinence after the cessation of radio-chemotherapy. In the case of metastatic tumours, current therapeutic recommendations are based on less robust evidence; with chemotherapy playing a major role. CONCLUSION These recommendations are permanently being reviewed, and each individual case must be discussed inside a multidisciplinary team.
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Affiliation(s)
| | | | | | | | | | | | | | - Didier Peiffert
- Cancerology Institute of Lorraine (Centre Alexis Vautrin), Vandœuvre-lès-Nancy, France
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Kim SS, Kim GE, Ko AH. A Patient with HIV-Associated Metastatic Anal Squamous Cell Carcinoma Receiving Multimodality Therapy with Curative Intent: Case Report and Review of the Literature. J Gastrointest Cancer 2017; 48:94-99. [PMID: 26961789 DOI: 10.1007/s12029-016-9814-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Affiliation(s)
- Sunhee S Kim
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 550 16th Street, 6th floor, Box 3211, San Francisco, CA, 94143, USA
| | - Grace E Kim
- Department of Pathology, University of California San Francisco, 1825 4th Street, San Francisco, CA, 94158, USA
| | - Andrew H Ko
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 550 16th Street, 6th floor, Box 3211, San Francisco, CA, 94143, USA. .,Division of Hematology/Oncology, San Francisco, CA, USA.
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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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Esser S, Kreuter A, Oette M, Gingelmaier A, Mosthaf F, Sautter-Bihl ML, Jongen J, Brockmeyer NH, Eldering G, Swoboda J, Postel N, Degen O, Schalk H, Jessen A, Knechten H, Thoden J, Stellbrink HJ, Schafberger A, Wieland U. German-Austrian guidelines on anal dysplasia and anal cancer in HIV-positive individuals: prevention, diagnosis, and treatment. J Dtsch Dermatol Ges 2016; 13:1302-19. [PMID: 26612810 DOI: 10.1111/ddg.12726] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Stefan Esser
- University Hospital Essen, HPSTD Outpatient Clinic, Department of Dermatology and Venereology, Essen, Germany
| | - Alexander Kreuter
- HELIOS St. Elisabeth Hospital Oberhausen, Department of Dermatology, Venereology, and Allergology, Oberhausen, Germany
| | - Mark Oette
- Augustinerinnen Hospital, Department of General Medicine, Gastroenterology; and Infectious Diseases, Cologne, Germany
| | - Andrea Gingelmaier
- Ludwig-Maximilians-University, University Hospital Munich, Department of Gynecology, Munich, Germany
| | - Franz Mosthaf
- Medical Specialist Practice for Hematology, Oncology, and Infectious Diseases, Karlsruhe, Germany
| | | | | | - Norbert H Brockmeyer
- Ruhr-University, St. Josef Hospital, Department of Dermatology, Venereology, and Allergology, Center for Sexual Health und Medicine, Bochum, Germany
| | | | | | | | - Olaf Degen
- University Hospital Hamburg-Eppendorf, Outpatient Clinic Center for Infectious Diseases, Hamburg, Germany
| | - Horst Schalk
- Medical Practice Center of General Medicine, Vienna, Austria
| | | | - Heribert Knechten
- Medical Practice for Internal Medicine and Infectious Diseases, Aachen, Germany
| | - Jan Thoden
- Medical Group Practice for Internal Medicine and Rheumatology, Freiburg, Germany
| | | | | | - Ulrike Wieland
- University Köln, Institute of Virology, National Reference Center for Papilloma and Polyomavirus, Cologne, Germany
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Houlihan OA, O'Neill BD. Chemoradiotherapy for anal squamous cell carcinoma. Surgeon 2016; 14:202-12. [DOI: 10.1016/j.surge.2016.03.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Revised: 03/10/2016] [Accepted: 03/18/2016] [Indexed: 01/27/2023]
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HIV positivity and anal cancer outcomes: A single-center experience. Am J Surg 2016; 211:886-93. [DOI: 10.1016/j.amjsurg.2016.01.009] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2015] [Revised: 01/20/2016] [Accepted: 01/23/2016] [Indexed: 11/24/2022]
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Fujiwara K, Koyama S, Fukuhara T, Miyake N, Yamasaki A, Kataoka H, Kitano H, Takeuchi H. Transoral surgery for HIV-infected patient with pharyngeal cancer and supraglottic cancer: A case study and literature review. ACTA OTO-LARYNGOLOGICA CASE REPORTS 2016. [DOI: 10.1080/23772484.2016.1259957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
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Esser S, Kreuter A, Oette M, Gingelmaier A, Mosthaf F, Sautter-Bihl ML, Jongen J, Brockmeyer NH, Eldering G, Swoboda J, Postel N, Degen O, Schalk H, Jessen A, Knechten H, Thoden J, Stellbrink HJ, Schafberger A, Wieland U. Deutsch-Österreichische S2k-Leitlinie: anale Dysplasien und Analkarzinome bei HIV-Infizierten: Prävention, Diagnostik und Therapie. J Dtsch Dermatol Ges 2015. [DOI: 10.1111/ddg.60_12726] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Affiliation(s)
- Stefan Esser
- Universitätsklinikum Essen, HPSTD-Ambulanz; Klinik für Dermatologie und Venerologie; Essen Deutschland
| | - Alexander Kreuter
- HELIOS St. Elisabeth Klinik Oberhausen; Klinik für Dermatologie, Venerologie und Allergologie; Oberhausen Deutschland
| | - Mark Oette
- Augustinerinnen Hospital, Klinik für Allgemeinmedizin; Gastroenterologie und Infektiologie; Köln Deutschland
| | - Andrea Gingelmaier
- Ludwig-Maximilians-Universität, Universitätsklinikum München; Klinik für Gynäkologie; München Deutschland
| | - Franz Mosthaf
- Facharztpraxis für Hämatologie; Onkologie und Infektiologie; Karlsruhe Deutschland
| | - Marie-Luise Sautter-Bihl
- Städtische Klinikum Karlsruhe; Klinik für Radioonkologie und Strahlentherapie; Karlsruhe Deutschland
| | | | - Norbert H. Brockmeyer
- Ruhr-Universität, St. Josef Krankenhaus, Klinik für Dermatologie; Venerologie und Allergologie, Zentrum für sexuelle Gesundheit und Medizin; Bochum Deutschland
| | | | | | | | - Olaf Degen
- Universitätsklinikum Hamburg-Eppendorf; Ambulanzzentrum Bereich Infektiologie; Hamburg Deutschland
| | - Horst Schalk
- Gruppenpraxis für Allgemeinmedizin; Wien Österreich
| | | | | | - Jan Thoden
- Gemeinschaftspraxis für Innere Medizin und Rheumatologie; Freiburg Deutschland
| | | | | | - Ulrike Wieland
- Universität Köln, Institut für Virologie; Nationales Referenzzentrum für Papillom- und Polyomaviren; Köln Deutschland
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Chen WY, Kuo SH, Shen CW, Huang BS, Lan KH, Liang HK, Wang CW. Good tolerance and long-term complete remission after definitive intensity-modulated radiotherapy for locally advanced head and neck cancer in a patient with human immunodeficiency virus infection: A case report and literature review. Head Neck 2015; 37:E186-E190. [PMID: 25821193 DOI: 10.1002/hed.24058] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2014] [Revised: 01/15/2015] [Accepted: 03/22/2015] [Indexed: 11/08/2022] Open
Abstract
BACKGROUND The main concerns with radiation therapy for head and neck cancer in human immunodeficiency virus (HIV)-infected patients include limited tumor response and profound mucosal or skin toxicities under severe immunocompromised status. METHODS In this study, we describe the clinicopathological features, chronological changes in HIV viral loads and CD4 counts, and treatment outcomes of definitive radiotherapy for locally advanced head and neck cancer in an HIV-infected patient. RESULTS Despite low CD4 counts (80 cells/µL), a combination of highly active antiretroviral therapy (HAART) and definitive concurrent chemoradiotherapy (70 Gy of simultaneously integrated boost intensity-modulated radiotherapy (IMRT), fluorouracil, and leucovorin) was well-tolerated. Grade 3 mucositis and dermatitis were resolved 2 weeks after treatment completion. The patient was alive and remained disease-free 31 months after treatment. CONCLUSION For patients with HIV diagnosed with locally advanced head and neck cancer, good tolerance and outcome can be achieved with definitive radiotherapy while on HAART.
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Affiliation(s)
- Wan-Yu Chen
- Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
- Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Sung-Hsin Kuo
- Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chia-Wei Shen
- Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Yun-Lin Branch, Taiwan
| | - Bing-Shen Huang
- Department of Radiation Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
| | - Keng-Hsueh Lan
- Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
- Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Hsiang-Kuang Liang
- Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
- Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chun-Wei Wang
- Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
- Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Radiology, National Taiwan University College of Medicine, Taipei, Taiwan
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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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Ünsal Ö, Türk B, Akpınar M, Bağlı M, Coşkun BU. Human Immunodeficiency Virus (HIV) Positive Case with Squamous Cell Larynx Cancer: Difficulties in the Choice of Treatment. Turk Arch Otorhinolaryngol 2015; 53:136-138. [PMID: 29391996 DOI: 10.5152/tao.2015.839] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2014] [Accepted: 06/24/2015] [Indexed: 11/22/2022] Open
Abstract
Squamous cell carcinoma of the larynx is rarely encountered in HIV (human immunodeficiency virus)-positive patients compared with HIV-associated malignancies. Standard protocols are absent for the management of laryngeal carcinoma in HIV-positive patients. HIV infection-associated immune suppression increases the mortality and morbidity of laryngeal carcinoma treatment. In the management of laryngeal carcinoma in HIV-positive patients, beside the clinical staging, the detection of CD4+ cell count is important. Regular antiretroviral treatment may have favorable effects in the management of laryngeal carcinoma. The treatment modality in the presented HIV-positive case with the diagnosis of laryngeal cancer was determined with a multidisciplinary approach.
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Affiliation(s)
- Özlem Ünsal
- Clinic of Otorhinolaryngology, Şişli Etfal Training and Research Hospital, İstanbul, Turkey
| | - Bilge Türk
- Clinic of Otorhinolaryngology, Şişli Etfal Training and Research Hospital, İstanbul, Turkey
| | - Meltem Akpınar
- Clinic of Otorhinolaryngology, Şişli Etfal Training and Research Hospital, İstanbul, Turkey
| | - Mustafa Bağlı
- Clinic of Otorhinolaryngology, Şişli Etfal Training and Research Hospital, İstanbul, Turkey
| | - Berna Uslu Coşkun
- Clinic of Otorhinolaryngology, Şişli Etfal Training and Research Hospital, İstanbul, Turkey
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Mangena M, Snyman L, Dreyer G, Bassa S, Becker P. The impact of HIV infection on women receiving radiation for cervical cancer. SOUTHERN AFRICAN JOURNAL OF GYNAECOLOGICAL ONCOLOGY 2015. [DOI: 10.1080/20742835.2015.1083697] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
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Abstract
OPINION STATEMENT Squamous cell carcinoma (SCCA) of the anal canal is an underrecognized malignancy that is growing in annual incidence. Over the years, combined chemoradiation has been the mainstay of treatment for locally advanced SCCA of the anal canal. Currently, the human papilloma virus (HPV) vaccine is recommended to prevent the development of HPV and its associated precancerous lesion(s). Patients diagnosed with the human immunodeficiency virus (HIV+) are prone to develop anal cancer due to their high risk of contracting HPV infection. We will focus on the development and management of SCCA of the anal canal (both localized and metastatic), including special details on HIV-positive patients. Highlights will include the role of targeted therapy based on available literature. Our objective is to aid practicing physicians in formulating a treatment plan for both locally advanced and metastatic patients.
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Affiliation(s)
- Shahab Ahmed
- The Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 426, Houston, TX, 77030, USA,
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Abstract
Despite effective highly active antiretroviral treatment, anal cancer incidence has recently strongly increased in HIV-infected population. Treatment strategy in HIV-infected patients does not differ from general population. HIV-infected patients treated by chemo-radiotherapy are exposed to high-grade toxicities and should be closely monitored to deliver the optimal treatment. Close collaboration between oncologist and infectiologist is highly recommended to adjust antiretroviral therapy if necessary.
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Shridhar R, Shibata D, Chan E, Thomas CR. Anal cancer: current standards in care and recent changes in practice. CA Cancer J Clin 2015; 65:139-62. [PMID: 25582527 DOI: 10.3322/caac.21259] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
Answer questions and earn CME/CNE The management of squamous cell carcinomas of the anal canal has evolved from surgery as first-line treatment to curative chemoradiation, with surgery reserved for salvage. Significant progress has been made in understanding how to most effectively deliver chemotherapy and reduce toxicity through advancements in radiation delivery. The purpose of this article is to review the multimodality approach to the diagnosis and management of anal cancer based on a review of the published data and in light of available guidelines.
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Affiliation(s)
- Ravi Shridhar
- Associate Professor, Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL
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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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Meernik C, Soliman AS, Ngoma T, Kahesa C, Mwaiselage J, Merajver SD. The changing pattern of ano-rectal cancer, squamous cell carcinoma of the eye, and Hodgkin's lymphoma as non-AIDS-defining cancers, by HIV status, in Tanzania over 11 years (2002-2012): a retrospective case-report study. Infect Agent Cancer 2014; 9:42. [PMID: 25926865 PMCID: PMC4414437 DOI: 10.1186/1750-9378-9-42] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2014] [Accepted: 11/03/2014] [Indexed: 12/01/2022] Open
Abstract
BACKGROUND In Tanzania, 5.1% of adults aged 15-49 are infected with HIV. While rates of HIV-related malignancies have declined globally with antiretroviral therapy (ART), including Tanzania, rates of non-AIDS-defining cancers (NADCs) are believed to have increased. Therefore, we determined trends of three NADCs in Tanzania: ano-rectal cancer, squamous cell carcinoma of the eye, and Hodgkin's lymphoma. METHODS This study was conducted at the Ocean Road Cancer Institute (ORCI) in Dar es Salaam. All medical records of patients diagnosed with ano-rectal cancer, squamous cell carcinoma of the eye, and Hodgkin's lymphoma between 2002 and 2012 were reviewed regarding HIV status, cancer clinical characteristics and management. Analysis was conducted to determine trends and proportions in these three NADCs and patient characteristics. RESULTS We identified 980 NADCs. The relative proportion of these three NADCs at ORCI out of all cancers treated increased from 2.37% in 2002 to a peak of 4.34% in 2009. The prevalence of HIV in patients diagnosed with these NADCs also increased-from 6.67% in 2002 to 20.87% in 2010-and 85% of squamous cell carcinoma of the eye cancer patients with a reported HIV status were HIV-positive. CONCLUSIONS The frequency and proportions of these three NADCs in Tanzania have increased over the past 11 years, as has the prevalence of HIV positivity amongst these NADC patients. The current and possibly increasing burden of NADCs in Tanzania and other low- and middle-income countries with high HIV rates should be a focus for future cancer prevention and control and HIV therapy programs.
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Affiliation(s)
- Clare Meernik
- />Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI USA
| | - Amr S Soliman
- />Department of Epidemiology, University of Nebraska Medical Center College of Public Health, Omaha, NE USA
| | - Twalib Ngoma
- />Ocean Road Cancer Institute, Dar es Salaam, Tanzania
| | | | | | - Sofia D Merajver
- />Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI USA
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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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Spithoff K, Cummings B, Jonker D, Biagi JJ. Chemoradiotherapy for squamous cell cancer of the anal canal: a systematic review. Clin Oncol (R Coll Radiol) 2014; 26:473-87. [PMID: 24721444 DOI: 10.1016/j.clon.2014.03.005] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2013] [Accepted: 01/30/2014] [Indexed: 11/26/2022]
Abstract
Squamous cell cancer of the anal canal is a rare tumour for which there remains uncertainty regarding optimal therapy. A systematic review was conducted to summarise the evidence examining concurrent chemotherapy and radiotherapy or different chemotherapy regimens in combination with radiotherapy. MEDLINE, EMBASE and conference proceedings were searched for relevant randomised controlled trials. Outcomes of interest were colostomy rate, local failure, overall survival, disease-free survival, adverse effects and quality of life. Six randomised controlled trials were identified. Two trials reported lower colostomy and local failure rates for concurrent 5-fluorouracil (5-FU) plus mitomycin C (MMC) and radiotherapy compared with radiotherapy alone. The omission of MMC from this regimen resulted in higher colostomy and local failure rates and lower disease-free survival. Induction chemotherapy followed by concurrent 5-FU plus cisplatin and radiotherapy resulted in a higher colostomy rate than concurrent 5-FU plus MMC and radiotherapy. Haematological toxicity rates were lower in patients who received radiotherapy with 5-FU alone or 5-FU plus cisplatin compared with 5-FU plus MMC. No benefit was seen for the addition of induction or maintenance chemotherapy to concurrent chemoradiotherapy. The available evidence continues to support the use of radiotherapy with concurrent 5-FU and MMC as standard treatment for cancer of the anal canal to decrease colostomy and local failure rates.
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Affiliation(s)
- K Spithoff
- Cancer Care Ontario Program in Evidence-based Care, McMaster University, Department of Oncology, Hamilton, Ontario, Canada.
| | - B Cummings
- Princess Margaret Hospital, Department of Radiation Oncology, Toronto, Ontario, Canada
| | - D Jonker
- The Ottawa Hospital Cancer Centre, Division of Medical Oncology, Ottawa, Ontario, Canada
| | - J J Biagi
- Cancer Centre of Southeastern Ontario, Kingston General Hospital, Division of Medical Oncology, Kingston, Ontario, Canada
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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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Buchs NC, Allal AS, Morel P, Gervaz P. Prevention, chemoradiation and surgery for anal cancer. Expert Rev Anticancer Ther 2014; 9:483-9. [DOI: 10.1586/era.09.4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Magné N, Chargari C, Levy A, Guy JB, Merrouche Y, Spano JP. Bevacizumab in HIV-positive patients: concerns about safety and potential for therapeutic use. J Chemother 2013; 26:253-5. [PMID: 24090564 DOI: 10.1179/1973947813y.0000000109] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Human immunodeficiency virus (HIV) patients have more aggressive presentation of colorectal cancer (CRC) and less favourable outcome. Bevacizumab is an antiangiogenic agent that has emerged as a major drug for metastatic CRC. However, few data are available on the safety of bevacizumab in HIV patients. In the light of a case study, we briefly draw intention on how angiogenesis inhibitors could interact with antiviral tri-therapy.
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Harris DA, Williamson J, Davies M, Evans MD, Drew P, Beynon J. Outcome of salvage surgery for anal squamous cell carcinoma. Colorectal Dis 2013; 15:968-73. [PMID: 23522325 DOI: 10.1111/codi.12222] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2012] [Accepted: 12/15/2012] [Indexed: 02/08/2023]
Abstract
AIM The purpose of this study was to examine factors related to treatment failure following chemoradiotherapy for squamous cancer and to compare the outcome of salvage surgery in one unit with national audit standards published by the Association of Coloproctology of Great Britain and Ireland (ACPGBI) (ACPGBI position statement for management of anal cancer. Colorectal Disease 2011; 13(Suppl. 1): 1-52). METHOD Patients with squamous cell carcinoma of the anus treated with radical intent between 1997 and 2010 in a single tertiary referral oncology institute were prospectively identified. Multivariate analysis was used to establish factors associated with treatment failure. Cancer-specific end-points after salvage surgery were determined by Kaplan-Meier survival analysis. RESULTS Ninety-five patients received chemoradiotherapy with radical intent with a 5-year overall survival of 83% (all stages) at a median follow up of 35 months. Of these, 11 (12%) required salvage surgery, five of whom were Stage T4 at presentation. Six patients had failed to respond to chemoradiotherapy and five presented with recurrence at a median of 10 (10-36) months. Only Stage T4 disease at presentation was predictive of the need for salvage surgery (OR 5.6, CI 4.9-6.3, P = 0.015). There was no surgical mortality and no delayed perineal healing where a myocutaneous flap was used. The resection margin was involved in one (9%) patient. The 5-year survival rate was 64%. Audit standards for case selection, local control, survival and perineal complications were achieved. CONCLUSION Long-term survival was achieved in two- thirds of patients following salvage surgery after failed primary chemoradiotherapy for anal cancer in a multidisciplinary oncological unit. Stage T4 disease at presentation strongly predicted the need for subsequent salvage intervention.
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Affiliation(s)
- D A Harris
- Department of Colorectal Surgery, Singleton Hospital, Swansea, UK.
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Abstract
OBJECTIVES To present an updated review of the incidence, risk factors, staging, diagnosis, and treatment of colon, rectal, and anal cancers, as well as nursing care associated with managing patients diagnosed with these malignancies. DATA SOURCES Published research reports, epidemiologic data, published patient management guidelines, and institution-based clinical tools. CONCLUSION While significant advances in the management of colon, rectal, and anal cancers in the past decade have extended patient survival, there remain some unanswered questions. Further clinical and molecular research will help individualize patient care, refining current therapeutic strategies and treatment decision-making aids while minimizing symptoms of disease and treatment. IMPLICATIONS FOR NURSING PRACTICE Nurses need to be familiar with risk factors, disease course, and current and emerging therapies to assist patients with treatment decision-making, and to anticipate and intervene in managing disease and treatment-induced problems. Early identification and management of distressing symptoms can help to avoid life-threatening effects and promote patient adherence to prescribed therapies; timely patient/family education may minimize anxiety and promote self-management.
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Abstract
Anal canal cancer is a rare cancer with incidence that continues to rise. This has been in large part due to increased prevalence of immunosuppressed conditions such as organ transplantation and human immunodeficiency virus along with transmission of the human papillomavirus. Identification of high-risk groups and close monitoring of these groups can help to detect earlier stages of cancer. Chemoradiation therapy remains the mainstay of treatment with excellent outcomes. Surgery for anal canal carcinoma remains as a salvage technique for failed chemoradiation or recurrent disease.
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Affiliation(s)
- Shawn P Webb
- Division of Colon and Rectal Surgery, Henry Ford Hospital, Detroit, Michigan
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50
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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: 46] [Impact Index Per Article: 3.5] [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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