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Vitek P, Kubes J, Ondrova B, Haas A. Very Late-Onset Serious Chronic Adverse Effects After Radical Chemoradiotherapy for Anal Canal Cancer. J Clin Med 2025; 14:3841. [PMID: 40507604 PMCID: PMC12156259 DOI: 10.3390/jcm14113841] [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] [Received: 04/12/2025] [Revised: 05/18/2025] [Accepted: 05/25/2025] [Indexed: 06/16/2025] Open
Abstract
Radical chemoradiotherapy has been used as a frontline treatment for squamous cell cancer of the anus for the last 30-40 years. Considerable acute and chronic adverse effects have been observed following radiotherapy using 2D and 3D techniques. A case of very late-onset severe chronic toxicity in a patient 26 years after radiotherapy is presented. The patient underwent radical chemoradiotherapy for squamous anal cancer stage T3N3M0 in 1998. In the anal region, cumulative doses up to 77.6 Gy (including electron boost) were administered. Durable complete regression of the disease was achieved. Fourteen years after treatment, the patient developed vast fibroatrophy of the anus and perineum, progressing within the subsequent four years to necrosis and sphincter loss. Twenty years after treatment, the asymptomatic osteonecrotic foci in the left femur appeared on MRI scans. Despite two courses of hyperbaric oxygen treatment, the fibroatrophy and subsequent necrosis of soft tissues remained progressive, but the osteonecrosis was stable. Twenty-six years after treatment, the progressive changes induced symptomatic osteomyelitis of the ischium and pubic bone. The patient now requires permanent supportive treatment. The presented case is exceptional in the very late-onset typical chronic adverse effects developing after non-conformal radiotherapy administered at high doses as part of contemporary treatment protocols. There is little evidence regarding the late onset of chronic adverse effects, since the follow-up period is usually shorter than that of the case presented. Moreover, a significant portion of patients do not survive to reach the late-onset period of adverse effects. The presented case shows that there may be long-term survivors of anal cancer in the population who were treated with outdated techniques and who still carry a risk of late-onset severe, progressive adverse effects.
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Affiliation(s)
- Pavel Vitek
- Proton Therapy Center Czech, 180 00 Prague, Czech Republic; (J.K.); (B.O.); (A.H.)
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2
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Metser U, Lukovic J, Mesci A, MacCrostie P, Chan R, Mak V, Avery L, Singnurkar A, Langer DL, Ly K, Kohan A. [ 18F]-FDG PET/CT in the Initial Staging of Squamous Cell Cancer of the Anal Canal: Results of a Prospective Multicenter Registry. J Nucl Med 2025; 66:537-542. [PMID: 40049747 DOI: 10.2967/jnumed.124.269289] [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: 12/05/2024] [Accepted: 01/29/2025] [Indexed: 04/03/2025] Open
Abstract
In patients with squamous cell carcinoma of the anal canal (ACC), disease stage influences treatment plans and determines prognosis. Our purpose was to determine the impact of PET on the initial staging of patients with presumed stages II-IV ACC and to assess the association of disease stage per conventional workup (CW) and PET imaging to patient outcomes. Methods: In this multicenter registry, patients with CW stages II-IV ACC or equivocal findings for a specific stage were included. Demographic data and stage according to the American Joint Committee on Cancer (AJCC) version 7 as determined by CW and PET were recorded and compared with overall survival (OS). For patients from 1 of the participating institutions, CW and PET stage according to AJCC versions 7-9 were compared with progression-free survival (PFS) and OS. Results: There were 813 patients included. PET upstaged 150 of 531 patients (28.2%) and downstaged 84 of 531 patients (15.8%) and assigned a specific stage to 200 of 232 patients (86.2%) with equivocal findings on CW. Stage IV on PET was predictive of significantly poorer OS (P = 0.005). For the 136 patients with staging according to AJCC versions 7-9, CW stages I-IV per versions 7-9 were not predictive of OS (P = 0.684, 0.329, and 0.083, respectively) or PFS (P = 0.622, 0.606, and 0.115, respectively). However, PET stages I-IV per versions 7-9 were associated with OS (P = 0.037, 0.003, 0.003, respectively) and PFS (P = 0.004, <0.001, <0.001, respectively), with version 9 best discriminating PFS for stages II and III. Conclusion: In patients with presumed stages II-IV ACC, PET stage differs in up to 44% from CW. PET assigns a specific stage in most patients with equivocal staging on CW. The PET-derived stage was predictive of PFS and OS. Because of its superior prognostication, PET should be used routinely to stage patients with ACC clinical stage II or above.
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Affiliation(s)
- Ur Metser
- University Medical Imaging Toronto, Joint Department of Medical Imaging, University Health Network, Sinai Health Systems, Women's College Hospital, University of Toronto, Toronto, Ontario, Canada;
| | - Jelena Lukovic
- Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
| | - Aruz Mesci
- Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
| | - Pamela MacCrostie
- Cancer Imaging Program, Ontario Health-Cancer Care Ontario, Toronto, Ontario, Canada
| | - Rosanna Chan
- Cancer Imaging Program, Ontario Health-Cancer Care Ontario, Toronto, Ontario, Canada
| | - Victor Mak
- Cancer Imaging Program, Ontario Health-Cancer Care Ontario, Toronto, Ontario, Canada
| | - Lisa Avery
- Department of Biostatistics, University Health Network, Toronto, Ontario, Canada; and
| | - Amit Singnurkar
- Department of Medical Imaging, Sunnybrook Health Sciences Center, University of Toronto, Toronto, Ontario, Canada
| | - Deanna L Langer
- Cancer Imaging Program, Ontario Health-Cancer Care Ontario, Toronto, Ontario, Canada
| | - Kara Ly
- University Medical Imaging Toronto, Joint Department of Medical Imaging, University Health Network, Sinai Health Systems, Women's College Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Andres Kohan
- University Medical Imaging Toronto, Joint Department of Medical Imaging, University Health Network, Sinai Health Systems, Women's College Hospital, University of Toronto, Toronto, Ontario, Canada
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Balci Topuz B, Sert F, Sezak M, Soylu M, Yalman D, Ozkok S. HPV status and immunohistochemical analysis of p16, p53 and PD‑L1 expression as prognostic biomarkers in patients with squamous cell anal cancer receiving definitive radiotherapy/chemoradiotherapy. Oncol Lett 2024; 28:395. [PMID: 38966586 PMCID: PMC11223008 DOI: 10.3892/ol.2024.14528] [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] [Received: 03/27/2024] [Accepted: 06/07/2024] [Indexed: 07/06/2024] Open
Abstract
Anal squamous cell carcinoma (SCC) treated with definitive radiotherapy (RT)/chemoradiotherapy (CRT) has shown high success rates, yet challenges such as treatment resistance and recurrence persist. The present study aimed to investigate the associations between immunohistochemical (IHC) evaluation, treatment response and prognosis in anal SCC. A retrospective cohort analysis included 42 patients with anal SCC treated at a single institution between 2006 and 2022. Human papillomavirus (HPV) status was determined, and the IHC analysis of p16, p53 and PD-L1 expression was conducted using formalin-fixed, paraffin-embedded biopsies. A complete response to RT/CRT was observed in 71.4% of patients. Recurrence occurred in 38.1% of cases, of which 7.1% had local-regional recurrence (LRR), 14.3% had distant recurrence (DR), and 16.7% had both LRR and DR. HPV positivity (71.4%) was significantly associated with p16 positivity. Lack of complete response was associated with HPV-negative status, p16-negative status, increased recurrence and DR. In addition, recurrence was significantly associated with p53-positive status, and p53 positivity was significantly associated with increased LRR. PD-L1 positivity, defined as a combined positive score (CPS) ≥1% was found in 73.8% of the patients, and exhibited significant associations with HPV positivity and p16 positivity. PD-L1 CPS ≥ 1% was also associated with an increased LRR. Univariate analysis revealed that age <65 years, a complete response and HPV positivity were associated with increased 5-year overall survival (OS), while a complete response, HPV positivity and p53-negative status were associated with increased 5-year disease-free survival (DFS). Multivariate analysis identified that age <65 years and HPV positivity are independent prognostic factors for 5-year OS, and a complete response and p53-negative status are independent prognostic factors for 5-year DFS. In conclusion, these findings suggust that the identification of HPV status and poor prognostic biomarkers at diagnosis may be used to guide personalized treatment strategies, with the combination of immunotherapy with standard CRT potentially providing improved outcomes.
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Affiliation(s)
- Beril Balci Topuz
- Department of Radiation Oncology, Ministry of Health Dr. Ersin Arslan Training and Research Hospital, Gaziantep 27090, Türkiye
| | - Fatma Sert
- Department of Radiation Oncology, Ege University Faculty of Medicine, Izmir 35100, Türkiye
| | - Murat Sezak
- Department of Pathology, Ege University Faculty of Medicine, Izmir 35100, Türkiye
| | - Mehmet Soylu
- Department of Microbiology, Ege University Faculty of Medicine, Izmir 35100, Türkiye
| | - Deniz Yalman
- Department of Radiation Oncology, Ege University Faculty of Medicine, Izmir 35100, Türkiye
| | - Serdar Ozkok
- Department of Radiation Oncology, Ege University Faculty of Medicine, Izmir 35100, Türkiye
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4
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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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5
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Anal cancer brachytherapy: from radon seeds to Papillon technique in a century. What does the future hold? Radiother Oncol 2022; 169:25-34. [DOI: 10.1016/j.radonc.2022.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 01/30/2022] [Accepted: 02/04/2022] [Indexed: 11/17/2022]
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6
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Marref I, Romain G, Jooste V, Vendrely V, Lopez A, Faivre J, Gerard JP, Bouvier AM, Lepage C. Outcomes of anus squamous cell carcinoma. Management of anus squamous cell carcinoma and recurrences. Dig Liver Dis 2021; 53:1492-1498. [PMID: 34193366 DOI: 10.1016/j.dld.2021.05.028] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 05/06/2021] [Accepted: 05/24/2021] [Indexed: 12/29/2022]
Abstract
BACKGROUND Little is known about the management of squamous cell carcinoma of the anal canal and its recurrence at a population level. The aim of this study was to draw a picture of management, recurrence and survival in squamous cell carcinoma of the anal canal. MATERIAL AND METHODS The 5-year probability of recurrences was estimated using the cumulative incidence function to consider competing risks of death. Net survival was estimated and a multivariate survival analysis was performed. The study was conducted using data of the Burgundy Digestive Cancer Registry. Overall, 273 squamous cell carcinomas of the anal canal registered between 1998 and 2014 were considered. RESULTS Overall, 80% of patients were treated with curative intent. Of these, 61% received chemoradiotherapy, 35% received radiotherapy and 4% received abdominoperineal resection alone. After these treatments, for cure the 5-year cumulative recurrence rate was 27% overall; it was 20% after chemoradiotherapy and 38% after radiotherapy. Five-year net survival was 71% overall; it was 81% after chemoradiotherapy and 55% after radiotherapy. CONCLUSIONS AND RELEVANCE Chemoradiotherapy was highly effective in routine practice. We confirm that it is difficult to distinguish between persistent active disease and local inflammation due to radiotherapy. Squamous cell carcinoma of the anal canal recurrences remains a substantial problem, highlighting the interest of prolonged surveillance. Aggressive management of recurrences may be beneficial.
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Affiliation(s)
- Imène Marref
- Digestive Cancer Registry of Burgundy, INSERM UMR 1231 EPICAD, University of Bourgogne-Franche Comté, University Hospital of Dijon, Dijon, France
| | - Gaëlle Romain
- Digestive Cancer Registry of Burgundy, INSERM UMR 1231 EPICAD, University of Bourgogne-Franche Comté, University Hospital of Dijon, Dijon, France
| | - Valerie Jooste
- Digestive Cancer Registry of Burgundy, INSERM UMR 1231 EPICAD, University of Bourgogne-Franche Comté, University Hospital of Dijon, Dijon, France
| | - Véronique Vendrely
- CHU de Bordeaux, Haut-Lévêque Hospital, Department of Radiotherapy, Pessac, 33604, France
| | - Anthony Lopez
- Gastroenterology and Hepatology Department, Centre Hospitalo-Universitaire de Nancy, Vandoeuvre-lès-Nancy, France
| | - Jean Faivre
- Digestive Cancer Registry of Burgundy, INSERM UMR 1231 EPICAD, University of Bourgogne-Franche Comté, University Hospital of Dijon, Dijon, France
| | | | - Anne-Marie Bouvier
- Digestive Cancer Registry of Burgundy, INSERM UMR 1231 EPICAD, University of Bourgogne-Franche Comté, University Hospital of Dijon, Dijon, France
| | - Côme Lepage
- Digestive Cancer Registry of Burgundy, INSERM UMR 1231 EPICAD, University of Bourgogne-Franche Comté, University Hospital of Dijon, Dijon, France; CHU de Bordeaux, Haut-Lévêque Hospital, Department of Radiotherapy, Pessac, 33604, France; Gastroenterology and Hepatology Department, Centre Hospitalo-Universitaire de Nancy, Vandoeuvre-lès-Nancy, France; Department of Radiotherapy, Centre A Lacassagne, Nice, France; Department of Hepatogastroenterology and Digestive Oncology and Gastroenterology, , University Hospital of Dijon, University of Bourgogne-Franche Comté, 14 Rue Paul Gaffarel, 21000 Dijon, France.
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7
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Trilla-Fuertes L, Gámez-Pozo A, Maurel J, Garcia-Carbonero R, Capdevila J, G-Pastrián L, Mendiola M, Peña C, López-Vacas R, Cuatrecasas M, García-Alfonso P, Ramos-Ruiz R, Llorens C, Ghanem I, Conill C, Heredia-Soto V, Campos-Barros Á, Fresno Vara JÁ, Feliu J. Description of the genetic variants identified in a cohort of patients diagnosed with localized anal squamous cell carcinoma and treated with panitumumab. Sci Rep 2021; 11:7402. [PMID: 33795829 PMCID: PMC8016846 DOI: 10.1038/s41598-021-86966-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Accepted: 03/11/2021] [Indexed: 11/09/2022] Open
Abstract
Squamous cell carcinoma is the most frequent histologic type of anal carcinoma. The standard of care since the 1970s has been a combination of 5-fluorouracil, mitomycin C, and radiotherapy. This treatment is very effective in T1/T2 tumors (achieving complete regression in 80–90% of tumors). However, in T3/T4 tumors, the 3-year relapse free survival rate is only 50%. The VITAL trial aimed to assess the efficacy and safety of panitumumab in combination with this standard treatment. In this study, 27 paraffin-embedded samples from the VITAL trial and 18 samples from patients from daily clinical practice were analyzed by whole-exome sequencing and the influence of the presence of genetic variants in the response to panitumumab was studied. Having a moderate- or high-impact genetic variant in PIK3CA seemed to be related to the response to panitumumab. Furthermore, copy number variants in FGFR3, GRB2 and JAK1 were also related to the response to panitumumab. These genetic alterations have also been studied in the cohort of patients from daily clinical practice (not treated with panitumumab) and they did not have a predictive value. Therefore, in this study, a collection of genetic alterations related to the response with panitumumab was described. These results could be useful for patient stratification in new anti-EGFR clinical trials.
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Affiliation(s)
| | - Angelo Gámez-Pozo
- Biomedica Molecular Medicine SL, Madrid, Spain.,Molecular Oncology and Pathology Lab, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain
| | - Joan Maurel
- Medical Oncology Department, Hospital Clinic of Barcelona, Translational Genomics and Targeted Therapeutics in Solid Tumors Group, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Rocio Garcia-Carbonero
- Medical Oncology Department, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), UCM, CNIO, CIBERONC, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Jaume Capdevila
- Medical Oncology Service, Vall Hebron Institute of Oncology (VHIO), Vall Hebron University Hospital, Barcelona, Spain
| | - Laura G-Pastrián
- Pathology Department, Hospital Universitario La Paz, Madrid, Spain.,Molecular Pathology and Therapeutic Targets Group, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain
| | - Marta Mendiola
- Molecular Pathology and Therapeutic Targets Group, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain.,Biomedical Research Networking Center On Oncology-CIBERONC, ISCIII, Madrid, Spain
| | - Cristina Peña
- Pathology Department, Hospital Universitario La Paz, Madrid, Spain
| | - Rocío López-Vacas
- Molecular Oncology and Pathology Lab, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain
| | - Miriam Cuatrecasas
- Pathology Department, Hospital Clínic Universitat de Barcelona, Villarroel 170, 08036, Barcelona, Spain
| | - Pilar García-Alfonso
- Medical Oncology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Ricardo Ramos-Ruiz
- Genomics Unit Cantoblanco, Parque Científico de Madrid, C/ Faraday 7, 28049, Madrid, Spain
| | - Carlos Llorens
- Biotechvana SL, Parque Científico de Madrid, C/ Faraday 7, 28049, Madrid, Spain
| | - Ismael Ghanem
- Medical Oncology Department, Hospital Universitario La Paz, Paseo de la Castellana 261, 28046, Madrid, Spain
| | - Carles Conill
- Radiotherapy Oncology Department, Hospital Clinic of Barcelona, Carrer de Villarroel 170, 08036, Barcelona, Spain
| | - Victoria Heredia-Soto
- Biomedical Research Networking Center On Oncology-CIBERONC, ISCIII, Madrid, Spain.,Translational Oncology Group, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain
| | - Ángel Campos-Barros
- Institute of Medical and Molecular Genetics, IdiPAZ, Unit 753, ISCIII, Hospital Universitario La Paz /& CIBERER, Paseo de la Castellana 261, 28046, Madrid, Spain
| | - Juan Ángel Fresno Vara
- Molecular Oncology and Pathology Lab, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain.,Biomedical Research Networking Center On Oncology-CIBERONC, ISCIII, Madrid, Spain
| | - Jaime Feliu
- Biomedical Research Networking Center On Oncology-CIBERONC, ISCIII, Madrid, Spain. .,Medical Oncology Department, Hospital Universitario La Paz, Paseo de la Castellana 261, 28046, Madrid, Spain. .,Cátedra UAM-Amgen, Universidad Autónoma de Madrid, Madrid, Spain.
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8
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Dee EC, Byrne JD, Wo JY. Evolution of the Role of Radiotherapy for Anal Cancer. Cancers (Basel) 2021; 13:1208. [PMID: 33801992 PMCID: PMC8001637 DOI: 10.3390/cancers13061208] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 03/05/2021] [Accepted: 03/06/2021] [Indexed: 12/11/2022] Open
Abstract
Prior to the 1980s, the primary management of localized anal cancer was surgical resection. Dr. Norman Nigro and colleagues introduced neoadjuvant chemoradiotherapy prior to abdominoperineal resection. Chemoradiotherapy 5-fluorouracil and mitomycin C afforded patients complete pathologic response and obviated the need for upfront surgery. More recent studies have attempted to alter or exclude chemotherapy used in the Nigro regimen to mitigate toxicity, often with worse outcomes. Reductions in acute adverse effects have been associated with marked advancements in radiotherapy delivery using intensity-modulated radiation therapy (IMRT) and image-guidance radiation delivery, resulting in increased tolerance to greater radiation doses. Ongoing trials are attempting to improve IMRT-based treatment of locally advanced disease with efforts to increase personalized treatment. Studies are also examining the role of newer treatment modalities such as proton therapy in treating anal cancer. Here we review the evolution of radiotherapy for anal cancer and describe recent advances. We also elaborate on radiotherapy's role in locally persistent or recurrent anal cancer.
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Affiliation(s)
| | - James D. Byrne
- Harvard Radiation Oncology Program, Harvard Medical School, Boston, MA 02115, USA;
| | - Jennifer Y. Wo
- Harvard Medical School, 25 Shattuck St., Boston, MA 02115, USA;
- Department of Radiation Oncology, Massachusetts General Hospital, 100 Blossom St., Boston, MA 02114, USA
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9
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Ko G, Sarkaria A, Merchant SJ, Booth CM, Patel SV. A systematic review of outcomes after salvage abdominoperineal resection for persistent or recurrent anal squamous cell cancer. Colorectal Dis 2019; 21:632-650. [PMID: 30689272 DOI: 10.1111/codi.14569] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Accepted: 01/12/2019] [Indexed: 02/08/2023]
Abstract
AIM Up to 30% of patients with squamous cell cancer of the anus (SCCA) will require a salvage abdominoperineal resection (APR) for either persistent or recurrent disease. The objective of this study was to assess cancer-related outcomes in patients with (i) persistent or (ii) recurrent SCCA. METHOD Embase and MEDLINE were searched. Publications were included if they assessed overall survival (OS), disease-free survival (DFS) and locoregional recurrence or metastatic disease after salvage APR for persistent or recurrent SCCA. RESULTS A total of 28 retrospective case series (study size ranged from nine to 111) met our inclusion criteria. The median time to salvage APR was 2.6 months [interquartile range (IQR) 2.6-5.0 months, six studies] for persistent disease and 27.6 months (IQR 15.0-32.7 months, five studies) for recurrent disease. The median 5-year OS from the time of salvage APR was 45.0% (IQR 32.0%-52.3%, 10 studies) for persistent disease and 51.0% (IQR 36.0%-60.9%, 11 studies) for recurrent disease. The median 5-year DFS following salvage APR was 44.0% (IQR 29.5%-53.0%, 10 studies) for all patients. Following salvage APR, the median locoregional recurrence rate was 23.5% (IQR 15.8%- 46.9%, 19 studies) and 9.0% (IQR 6.4%-13.3%, 16 studies) of patients developed metastatic disease after salvage APR. CONCLUSION Our review characterizes the best evidence for outcomes following salvage APR for patients with persistent or recurrent SCCA. The evidence is limited by the quality of included studies, as many were single centre case series.
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Affiliation(s)
- G Ko
- Department of Surgery, Queen's University, Kingston, Ontario, Canada
| | - A Sarkaria
- School of Medicine, Queen's University, Kingston, Ontario, Canada
| | - S J Merchant
- Department of Surgery, Queen's University, Kingston, Ontario, Canada.,Department of Oncology, Queen's University, Kingston, Ontario, Canada
| | - C M Booth
- Department of Oncology, Queen's University, Kingston, Ontario, Canada
| | - S V Patel
- Department of Surgery, Queen's University, Kingston, Ontario, Canada.,Department of Oncology, Queen's University, Kingston, Ontario, Canada
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10
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Valvo F, Ciurlia E, Avuzzi B, Doci R, Ducreux M, Roelofsen F, Roth A, Trama A, Wittekind C, Bosset JF. Cancer of the anal region. Crit Rev Oncol Hematol 2019; 135:115-127. [DOI: 10.1016/j.critrevonc.2018.12.007] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Revised: 12/06/2018] [Accepted: 12/19/2018] [Indexed: 11/25/2022] Open
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11
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Pan YB, Maeda Y, Wilson A, Glynne-Jones R, Vaizey CJ. Late gastrointestinal toxicity after radiotherapy for anal cancer: a systematic literature review. Acta Oncol 2018; 57:1427-1437. [PMID: 30264638 DOI: 10.1080/0284186x.2018.1503713] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
INTRODUCTION There is a paucity of data on incidence and mechanisms of long-term gastrointestinal consequences after chemoradiotherapy for anal cancer. Most of the adverse effects reported were based on traditional external beam radiotherapy whilst only short-term follow-ups have been available for intensity-modulated radiotherapy, and there is lack of knowledge about consequences of dose-escalation radiotherapy. METHOD A systematic literature review. RESULTS Two thousand nine hundred and eighty-five titles (excluding duplicates) were identified through the search; 130 articles were included in this review. The overall incidence of late gastrointestinal toxicity was reported to be 7-64.5%, with Grade 3 and above (classified as severe) up to 33.3%. The most commonly reported late toxicities were fecal incontinence (up to 44%), diarrhea (up to 26.7%), and ulceration (up to 22.6%). Diarrhea, fecal incontinence and buttock pain were associated with lower scores in radiotherapy specific quality of life scales (QLQ-CR29, QLQ-C30, and QLQ-CR38) compared to healthy controls. Intensity-modulated radiation therapy appears to reduce late toxicity. CONCLUSION Late gastrointestinal toxicities are common with severe toxicity seen in one-third of the patients. These symptoms significantly impact on patients' quality of life. Prospective studies with control groups are needed to elucidate long-term toxicity.
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Affiliation(s)
- Yi Bin Pan
- Sir Alan Parks Physiology Unit, St. Mark’s Hospital, Harrow, UK
- Longhua Hospital, Shanghai University of TCM, Shanghai, China
| | - Yasuko Maeda
- Sir Alan Parks Physiology Unit, St. Mark’s Hospital, Harrow, UK
- Imperial College London, London, UK
| | - Ana Wilson
- Imperial College London, London, UK
- Wolfson Unit of Endoscopy, St. Mark’s Hospital, Harrow, UK
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12
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Jones MP, Martin J, Foo K, Estoesta P, Holloway L, Jameson M. The impact of contour variation on tumour control probability in anal cancer. Radiat Oncol 2018; 13:97. [PMID: 29776418 PMCID: PMC5960192 DOI: 10.1186/s13014-018-1033-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2017] [Accepted: 04/18/2018] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND While intensity modulated radiotherapy (IMRT) has been widely adopted for the treatment of anal cancer (AC), the added contour complexity poses potential risks. This study investigates the impact of contour variation on tumour control probability (TCP) when using IMRT for AC. METHODS Nine Australian centres contoured a single computed tomography dataset of a patient with AC. The same optimised template-based IMRT planning protocol was applied to each contour set to generate nine representative treatment plans and their corresponding dose volume histograms. A geometric analysis was performed on all contours. The TCP was calculated for each plan using the linear quadratic and logitEUD model. RESULTS The median concordance index (CI) for the bladder, head and neck of femur, bone marrow, small bowel and external genitalia was 0.94, 0.88, 0.84, 0.65 and 0.65, respectively. The median CI for the involved nodal, primary tumour and elective clinical target volumes were 0.85, 0.77 and 0.71, respectively. Across the nine plans, the TCP was not significantly different. Variation in TCP between plans increased as tumour cell load increased or radiation dose decreased. CONCLUSIONS When using IMRT for AC, contour variations generated from a common protocol within the limits of minor deviations do not appear to have a significant impact on TCP. Contouring variations may be more critical with increasing tumour cell load or reducing radiotherapy dose.
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Affiliation(s)
- Michael P Jones
- School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, Australia. .,Department of Radiation Oncology, Calvary Mater Newcastle, Waratah, NSW, Australia.
| | - Jarad Martin
- School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, Australia.,Department of Radiation Oncology, Calvary Mater Newcastle, Waratah, NSW, Australia
| | - Kerwyn Foo
- Department of Radiation Oncology, Chris O'Brien Lifehouse, Camperdown, NSW, Australia
| | - Patrick Estoesta
- Department of Radiation Oncology, Chris O'Brien Lifehouse, Camperdown, NSW, Australia
| | - Lois Holloway
- Liverpool and Macarthur Cancer Therapy Centres, Liverpool, NSW, Australia.,Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia.,South West Clinical School, Faculty of Medicine, University of New South Wales, Kensington, NSW, Australia.,Institute of Medical Physics, School of Physics, University of Sydney, Camperdown, NSW, Australia.,Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW, Australia
| | - Michael Jameson
- Liverpool and Macarthur Cancer Therapy Centres, Liverpool, NSW, Australia.,Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia.,South West Clinical School, Faculty of Medicine, University of New South Wales, Kensington, NSW, Australia
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Geh I, Gollins S, Renehan A, Scholefield J, Goh V, Prezzi D, Moran B, Bower M, Alfa-Wali M, Adams R. Association of Coloproctology of Great Britain & Ireland (ACPGBI): Guidelines for the Management of Cancer of the Colon, Rectum and Anus (2017) - Anal Cancer. Colorectal Dis 2017; 19 Suppl 1:82-97. [PMID: 28632308 DOI: 10.1111/codi.13709] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Ian Geh
- Queen Elizabeth Hospital, Birmingham, UK
| | | | - Andrew Renehan
- University of Manchester and Christie Hospital, Manchester, UK
| | - John Scholefield
- University of Nottingham and Queens Medical Centre, Nottingham, UK
| | - Vicky Goh
- King's College and Guy's & St Thomas' Hospital, London, UK
| | | | - Brendan Moran
- Basingstoke & North Hampshire Hospital, Basingstoke, UK
| | - Mark Bower
- Imperial College and Chelsea & Westminster Hospital, London, UK
| | | | - Richard Adams
- Cardiff University and Velindre Cancer Centre, Cardiff, UK
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14
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Perianal synovial sarcoma treated postoperatively with Iodine-125 brachytherapy: Technical details. Brachytherapy 2017; 16:565-571. [DOI: 10.1016/j.brachy.2017.02.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2017] [Revised: 02/20/2017] [Accepted: 02/22/2017] [Indexed: 11/19/2022]
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15
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Glynne-Jones R, Sebag-Montefiore D, Meadows HM, Cunningham D, Begum R, Adab F, Benstead K, Harte RJ, Stewart J, Beare S, Hackshaw A, Kadalayil L. Best time to assess complete clinical response after chemoradiotherapy in squamous cell carcinoma of the anus (ACT II): a post-hoc analysis of randomised controlled phase 3 trial. Lancet Oncol 2017; 18:347-356. [PMID: 28209296 PMCID: PMC5337624 DOI: 10.1016/s1470-2045(17)30071-2] [Citation(s) in RCA: 114] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2016] [Revised: 11/08/2016] [Accepted: 11/15/2016] [Indexed: 12/18/2022]
Abstract
BACKGROUND Guidelines for anal cancer recommend assessment of response at 6-12 weeks after starting treatment. Using data from the ACT II trial, we determined the optimum timepoint to assess clinical tumour response after chemoradiotherapy. METHODS The previously reported ACT II trial was a phase 3 randomised trial of patients of any age with newly diagnosed, histologically confirmed, squamous cell carcinoma of the anus without metastatic disease from 59 centres in the UK. We randomly assigned patients (by minimisation) to receive either intravenous mitomycin (one dose of 12 mg/m2 on day 1) or intravenous cisplatin (one dose of 60 mg/m2 on days 1 and 29), with intravenous fluorouracil (one dose of 1000 mg/m2 per day on days 1-4 and 29-32) and radiotherapy (50·4 Gy in 28 daily fractions); and also did a second randomisation after initial therapy to maintenance chemotherapy (fluorouracil and cisplatin) or no maintenance chemotherapy. The primary outcome was complete clinical response (the absence of primary and nodal tumour by clinical examination), in addition to overall survival and progression-free survival from time of randomisation. In this post-hoc analysis, we analysed complete clinical response at three timepoints: 11 weeks from the start of chemoradiotherapy (assessment 1), 18 weeks from the start of chemoradiotherapy (assessment 2), and 26 weeks from the start of chemoradiotherapy (assessment 3) as well as the overall and progression-free survival estimates of patients with complete clinical response or without complete clinical response at each assessment. We analysed both the overall trial population and a subgroup of patients who had attended each of the three assessments by modified intention-to-treat. This study is registered at controlled-trials.com, ISRCTN 26715889. FINDINGS We enrolled 940 patients from June 4, 2001, until Dec 16, 2008. Complete clinical response was achieved in 492 (52%) of 940 patients at assessment 1 (11 weeks), 665 (71%) of patients at assessment 2 (18 weeks), and 730 (78%) of patients at assessment 3 (26 weeks). 691 patients attended all three assessments and in this subgroup, complete clinical response was reported in 441 (64%) patients at assessment 1, 556 (80%) at assessment 2, and 590 (85%) at assessments 3. 151 (72%) of the 209 patients who had not had a complete clinical response at assessment 1 had a complete clinical response by assessment 3. In the overall trial population of 940 patients, 5 year overall survival in patients who had a clinical response at assessments 1, 2, 3 was 83% (95% CI 79-86), 84% (81-87), and 87% (84-89), respectively and was 72% (66-78), 59% (49-67), and 46% (37-55) for patients who did not have a complete clinical response at assessments 1, 2, 3, respectively. In the subgroup of 691 patients, 5 year overall survival in patients who had a clinical response at assessment 1, 2, 3 was 85% (81-88), 86% (82-88), and 87% (84-90), respectively, and was 75% (68-80), 61% (50-70), and 48% (36-58) for patients who did not have a complete clinical response at assessment 1, 2, 3, respectively. Similarly, progression-free survival in both the overall trial population and the subgroup was longer in patients who had a complete clinical response, compared with patients who did not have a complete clinical response, at all three assessments. INTERPRETATION Many patients who do not have a complete clinical response when assessed at 11 weeks after commencing chemoradiotherapy do in fact respond by 26 weeks, and the earlier assessment could lead to some patients having unnecessary surgery. Our data suggests that the optimum time for assessment of complete clinical response after chemoradiotherapy for patients with squamous cell carcinoma of the anus is 26 weeks from starting chemoradiotherapy. We suggest that guidelines should be revised to indicate that later assessment is acceptable. FUNDING Cancer Research UK.
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Affiliation(s)
| | | | - Helen M Meadows
- Cancer Research UK and University College London Cancer Trials Centre, London, UK
| | | | - Rubina Begum
- Cancer Research UK and University College London Cancer Trials Centre, London, UK
| | - Fawzi Adab
- North Staffordshire Royal Infirmary, Stoke, UK
| | | | | | | | - Sandy Beare
- Cancer Research UK and University College London Cancer Trials Centre, London, UK
| | - Allan Hackshaw
- Cancer Research UK and University College London Cancer Trials Centre, London, UK
| | - Latha Kadalayil
- Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, UK
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17
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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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Glynne-Jones R, Saleem W, Harrison M, Mawdsley S, Hall M. Background and Current Treatment of Squamous Cell Carcinoma of the Anus. Oncol Ther 2016; 4:135-172. [PMID: 28261646 PMCID: PMC5315080 DOI: 10.1007/s40487-016-0024-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2016] [Indexed: 12/19/2022] Open
Abstract
In this review, a summary of our current understanding of squamous cell carcinoma of the anus (SCCA) and the advances in our knowledge of SCCA regarding screening, prevention, the role of the immune system, current treatment and the potential for novel targets are discussed. The present standard of care in terms of treatment is 5-fluorouracil (5-FU) and mitomycin C (MMC) concurrently with radiation, which results in a high level of disease control for small early cancers. Preservation of the anal sphincter is achieved in the majority, although anorectal function is often impaired. Although evidence from prospective studies to support a change in the treatment strategy is lacking, patients with HPV-negative SCCA appear to be less responsive to chemoradiation (CRT) and relapse more frequently. In contrast, HPV-positive tumours usually fare better, but oncological outcomes are modified by smoking and immune incompetence. There is current interest in escalating the radiotherapy dose for larger, more advanced tumours, and de-escalating treatment for HPV-positive tumours. The use of novel immunological treatments to target the underlying different molecular pathways of HPV-positive cancers is exciting.
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Affiliation(s)
- Rob Glynne-Jones
- Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, Middlesex UK
| | - Waqar Saleem
- Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, Middlesex UK
| | - Mark Harrison
- Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, Middlesex UK
| | - Suzy Mawdsley
- Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, Middlesex UK
| | - Marcia Hall
- Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, Middlesex UK
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Concomitant chemoradiotherapy with Cisplatin plus 5-Fluorouracil for anal squamous cell carcinoma. J Gastrointest Cancer 2016; 46:156-60. [PMID: 25810165 DOI: 10.1007/s12029-015-9707-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
OBJECTIVE The objective of this study was to evaluate the results of combined chemoradiotherapy using 5-fluorouracil and cisplatin with radiation in treatment of anal squamous cell carcinoma in terms of local control, survival, and toxicity. PATIENTS AND METHODS This study included 32 patients with histologically confirmed locally advanced anal squamous cell carcinoma (T1-4 with any N). They received chemotherapy consisted of 5-fluorouracil 1000 mg/m(2)/day on the first 5 and last 5 days of RT, cisplatin 75 mg/m(2) on days 2 and 30. External beam RT consisted of 45Gy/f/25 sessions/5 sessions per week. A boost of 9Gy/5 sessions was given to those who developed complete or partial response. RESULTS Median age was 55 years with female to male ratio 2.2:1. Fifty-six percent of them had ECOGPS of 1; moderately differentiated pathology was the most common one (53 %). Thirteen patients (40.6 %) presented with N0 and 56 % presented with T2. None of the patients died of acute complications and none developed grade 4 toxicity. Non-hematological complications were more common than hematological ones. Dermatitis was the most common toxicity (59.3 %) than diarrhea and neurologic one (40.7 %). Anemia was the most frequent hematological adverse event (37.5 %). Complete response was reported in 81.2 %. After median follow-up of 25 months, local recurrence was observed in five patients (15.6 %) as the following: three in the anal canal and two in the inguinal lymph nodes. Three patients (9.4 %) developed distant metastasis (two in the liver and one in the lung), while one patient (3 %) had both local and distant metastases. Three-year overall survival rate (OS) was 81.3 %, while 3-year progression-free survival (PFS) rate was 72 %, and colostomy-free survival was 90 %. CONCLUSION Concomitant chemoradiotherapy of 5-fluorouracil and cisplatin with radiotherapy is a highly effective and well-tolerated treatment of anal cancer. But further studies with larger number of patients are needed to support the indication to treat anal cancer using this regimen.
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Lower Gastrointestinal Brachytherapy: Anus. Brachytherapy 2016. [DOI: 10.1007/978-3-319-26791-3_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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21
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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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Leon O, Guren M, Hagberg O, Glimelius B, Dahl O, Havsteen H, Naucler G, Svensson C, Tveit KM, Jakobsen A, Pfeiffer P, Wanderås E, Ekman T, Lindh B, Balteskard L, Frykholm G, Johnsson A. Anal carcinoma - Survival and recurrence in a large cohort of patients treated according to Nordic guidelines. Radiother Oncol 2015; 113:352-8. [PMID: 25499203 DOI: 10.1016/j.radonc.2014.10.002] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2014] [Revised: 10/01/2014] [Accepted: 10/05/2014] [Indexed: 12/20/2022]
Abstract
OBJECTIVE To evaluate treatment outcome in a large population-based cohort of patients with anal cancer treated according to Nordic guidelines. MATERIAL Clinical data were collected on 1266 patients with anal squamous cell carcinoma diagnosed from 2000 to 2007 in Sweden, Norway and Denmark. 886 of the patients received radiotherapy 54-64Gy with or without chemotherapy (5-fluorouracil plus cisplatin or mitomycin) according to different protocols, stratified by tumor stage. RESULTS High age, male gender, large primary tumor, lymph node metastases, distant metastases, poor performance status, and non-inclusion into a protocol were all independent factors associated with worse outcome. Among patients treated according to any of the protocols, the 3-year recurrence-free survival ranged from 63% to 76%, with locoregional recurrences in 17% and distant metastases in 11% of patients. The highest rate of inguinal recurrence (11%) was seen in patients with small primary tumors, treated without inguinal irradiation. CONCLUSIONS Good treatment efficacy was obtained with Nordic, widely implemented, guidelines for treatment of anal cancer. Inguinal prophylactic irradiation should be recommended also for small primary tumors.
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Affiliation(s)
- Otilia Leon
- Department of Oncology, Skåne University Hospital, Lund, Sweden
| | - Marianne Guren
- Department of Oncology, Oslo University Hospital, Norway
| | | | | | - Olav Dahl
- Department of Oncology, Haukeland University Hospital, Bergen, Norway
| | | | - Gisela Naucler
- Department of Oncology, Karolinska University Hospital, Stockholm, Sweden
| | - Christer Svensson
- Department of Oncology, Karolinska University Hospital, Stockholm, Sweden
| | | | | | - Per Pfeiffer
- Department of Oncology, Odense Hospital, Denmark
| | - Eva Wanderås
- Department of Oncology, Oslo University Hospital, Norway
| | - Tor Ekman
- Department of Oncology, Sahlgrenska University Hospital, Göteborg, Sweden
| | - Birgitta Lindh
- Department of Oncology, Norrland University Hospital, Umeå, Sweden
| | - Lise Balteskard
- Centre for Clinical Documentation and Evaluation, Northern Regional Health Authority, Tromsö, Norway
| | - Gunilla Frykholm
- Department of Oncology, St. Olav's University Hospital, Trondheim, Norway
| | - Anders Johnsson
- Department of Oncology, Skåne University Hospital, Lund, Sweden.
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Jones M, Hruby G, Stanwell P, Gallagher S, Wong K, Arm J, Martin J. Multiparametric MRI as an outcome predictor for anal canal cancer managed with chemoradiotherapy. BMC Cancer 2015; 15:281. [PMID: 25885556 PMCID: PMC4423099 DOI: 10.1186/s12885-015-1244-7] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2014] [Accepted: 03/23/2015] [Indexed: 11/20/2022] Open
Abstract
Background Organ-preserving chemo-radiotherapy (CRT) is the standard of care for non-metastatic anal squamous cell carcinoma (SCC). The optimal dosing schedules are yet to be determined. To improve local control rates, dose escalation has been investigated but found to not increase efficacy at the expense of increased toxicity for an unselected patient population. Diffusion weighted imaging (DWI) and dynamic contrast enhanced (DCE) Magnetic Resonance Imaging (MRI) performed during CRT have early data suggesting it to be an effective tool in predicting later tumour response for SCC in related body sites. By performing multi-parametric MRI (mpmMRI) incorporating standard morphological, DWI and DCE sequences, we aim to determine whether the early changes in multi-parametric parameters during CRT can predict for later response in anal SCC. This may create opportunities to investigate treatment adaptation, either intensification or de-escalation, during CRT. Methods/Design This protocol describes a prospective non-interventional multi-centre single-arm clinical trial. Twenty eligible patients with histologically confirmed non-metastatic anal SCC will receive standard definitive CRT and undergo multi-parametric MRI’s at the following 4 time points; prior to treatment, during the second and fourth weeks of treatment and 6-8 weeks following treatment. Complete response will be defined by the absence of tumour persistence or recurrence as determined by clinical examination at 6 months. Images will be retrospectively analysed to determine the apparent diffusion coefficient and tumour perfusion coefficients (Ktrans and Kep) at each time point. The Mann-Whitney-Wilcoxon Test will be utilised to compare the change in these parameters for responder’s verses non-responders. Discussion If validated, mpmMRI, along with other risk factors, can be used to stratify patients and guide radiation dosing in a prospective trial. Informed individualisation of treatment intensity should help us achieve our goals of improved efficacy and reduced toxicity. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12614001219673 (19/11/2014).
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Affiliation(s)
- Michael Jones
- Radiation Oncology, Royal Prince Alfred Hospital, Salisbury Road, Camperdown, NSW, 2050, Australia.
| | - George Hruby
- Radiation Oncology, Chris O'brien Lifehouse, Missenden Road, Camperdown, NSW, 2050, Australia.
| | - Peter Stanwell
- Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, 2308, Australia.
| | - Sarah Gallagher
- Calvary Mater Newcastle, Edith Street, Waratah, NSW, 2298, Australia.
| | - Karen Wong
- Radiation Oncology, Liverpool Hospital, Corner of Elizabeth and Goulburn Streets, Liverpool, NSW, 2170, Australia.
| | - Jameen Arm
- Radiation Oncology, Calvary Mater Newcastle, Edith Street, Waratah, NSW, 2298, Australia.
| | - Jarad Martin
- Radiation Oncology, Calvary Mater Newcastle, Edith Street, Waratah, NSW, 2298, Australia.
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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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Arana de la Torre M, Jiménez Escovar F, García González JM, Alvarez Abad I, Colina Alonso A. Anal squamous cell carcinoma in chronic severe perianal Crohn's disease. Cir Esp 2015; 94:198-200. [PMID: 25702309 DOI: 10.1016/j.ciresp.2014.12.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2014] [Revised: 12/14/2014] [Accepted: 12/28/2014] [Indexed: 10/24/2022]
Affiliation(s)
- María Arana de la Torre
- Servicio de Cirugía General y del Aparato Digestivo, Hospital de Cruces, Baracaldo, Vizcaya, España.
| | - Fernando Jiménez Escovar
- Servicio de Cirugía General y del Aparato Digestivo, Hospital de Cruces, Baracaldo, Vizcaya, España
| | | | - Irene Alvarez Abad
- Servicio de Cirugía General y del Aparato Digestivo, Hospital de Cruces, Baracaldo, Vizcaya, España
| | - Alberto Colina Alonso
- Servicio de Cirugía General y del Aparato Digestivo, Hospital de Cruces, Baracaldo, Vizcaya, España
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26
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Squamous Cell Carcinoma of the Anal Canal. Surg Oncol 2015. [DOI: 10.1007/978-1-4939-1423-4_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Radiochemotherapy in Anal Cancer: cCR, clinical outcomes and quality of life using two different treatment schedules. Rep Pract Oncol Radiother 2014; 20:128-34. [PMID: 25859401 DOI: 10.1016/j.rpor.2014.11.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2014] [Revised: 09/23/2014] [Accepted: 11/03/2014] [Indexed: 12/27/2022] Open
Abstract
AIM Main endpoint was a response rate to therapy; secondary endpoints were disease-free survival, overall survival, acute and late toxicities, specially in terms of anorectal and urinary continence. BACKGROUND Radiochemotherapy for anal cancer achieves a good clinical response, locoregional control, anal function preservation. However, oncologic outcomes can differ using radiotherapy plus fluorouracil and mytomicin vs. cisplatin and fluorouracil. METHODS Between 2000 and 2012, 27 anal cancer patients receiving radiotherapy combined with two different radiochemotherapy schedules, fluorouracil and mytomicin (group A) and cisplatin plus fluorouracil (group B). The Kaplan-Meier method was also used to estimate local control, overall survival and disease free survival. Statistical significance between curves was evaluated using the Log-rank test. RESULTS Complete pathological response was found in 85.2% of patients, with higher rates of response in the group A (100% vs. 63.6%, p = 0.039). No significantly difference was found between the two groups for the other endpoints. Low rates of both acute and late toxicities were recorded. CONCLUSION Radiotherapy plus fluorouracil and mytomicin provide a better complete pathological response than radiotherapy plus cisplatin and fluorouracil and a greater rate of anal sphincter function preservation. Globally, radiochemotherapy of the anal cancer provides excellent clinical outcomes with a good profile of acute and late toxicity, without difference between the two groups studied.
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Jederán É, Lővey J, Szentirmai Z, Hitre E, Léránt G, Horváth K, Gődény M. The role of MRI in the assessment of the local status of anal carcinomas and in their management. Pathol Oncol Res 2014; 21:571-9. [PMID: 25354914 DOI: 10.1007/s12253-014-9857-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2013] [Accepted: 10/21/2014] [Indexed: 11/28/2022]
Abstract
This study aims to define the role of Magnetic Resonance (MR) examinations in the assessment and therapy of anal cancer (AC), and to present the main features of the MR examinations and the typical tumor spread pattern. The MR examinations of 67 anal cancer patients with histologically confirmed planocellular cancer were analyzed retrospectively. The tumor size and the signal intensity, the nodal status were examined before and after the treatment, and in recidive tumors (N = 13). At the time of the diagnosis the primary tumor was in early stage (Tis, T1, T2) in 71.5 % of the cases, and it was localized in 97 %. In 97.4 % of the cases the tumor had relatively increased signal intensities compared to the adjacent muscles. Patients received chemo-radiotherapy (CRT). After CRT in 26 out of 39 patients (66.7 %) the size of the tumor decreased (in 75 %), and the signal intensity decreased on the T2 weighted (T2w) images. In the residual tumor cases (19/39) verified 6 patients out of 19 had further decrease in size, and signal intensity a year after the end of the therapy. The MR examination plays a key role in the therapy of AC, by assessing the precise local status, the possible recidive tumors, and monitoring the therapy.
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Affiliation(s)
- É Jederán
- Department of Diagnostic Radiology, National Institute of Oncology, Budapest, Hungary,
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Cooper R, Casanova N, Sebag-Montefiore D. Chemoradiotherapy for anal cancer: clinical trials past, present and future. COLORECTAL CANCER 2014. [DOI: 10.2217/crc.14.16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
SUMMARY Anal cancer is a rare cancer whose incidence is increasing in the UK. It is associated with human papilloma virus infection and smoking and is more common in women and immunosuppressed individuals, including those with transplants and HIV infection. The current standard of care is chemoradiotherapy (CRT) to the pelvis with surgery reserved for patients where CRT is contraindicated or as salvage treatment for residual disease or recurrence post-CRT. Radiotherapy combined with mitomycin-C and 5-fluorouracil has emerged as the standard of care following a series of six well-conducted Phase III trials. Trials have shown no benefit for cisplatin-based combination regimens either concurrently, adjuvantly or neoadjuvantly.
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Affiliation(s)
- Rachel Cooper
- Department of Clinical Oncology, St James's Institute of Oncology, St James's University Hospital, Leeds, LS7 9TF, UK
| | - Nathalie Casanova
- Department of Clinical Oncology, St James's Institute of Oncology, St James's University Hospital, Leeds, LS7 9TF, UK
| | - David Sebag-Montefiore
- Department of Clinical Oncology, St James's Institute of Oncology, St James's University Hospital, Leeds, LS7 9TF, UK
- Leeds Institute of Cancer & Pathology, University of Leeds, St James's University Hospital, Leeds, LS7 9TF, UK
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Metastatic squamous cell carcinoma of the anus to the lung confirmed with allelotyping. Case Rep Pathol 2014; 2014:608521. [PMID: 24660084 PMCID: PMC3934382 DOI: 10.1155/2014/608521] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2013] [Accepted: 01/02/2014] [Indexed: 11/18/2022] Open
Abstract
Histopathologic techniques are insufficient for distinguishing primary squamous cell carcinoma (SCC) from metastatic SCC, which is clinically important. A patient with SCC of the anus was found to also have SCC of the lung, and the question of metastatic versus synchronous primary diseases was raised. Immunohistochemical and hematoxylin and eosin (H&E) staining on sections of tissue could not discriminate between the two entities. Immunostain for p16 and chromogenic in situ hybridization for human papillomavirus (HPV) type 16 were positive in both tumors. Additionally, allelotyping for loss of heterozygosity displayed similar findings and confirmed the histopathological impression of anal SCC metastasis to the lung. The patient was treated with palliative chemotherapy instead of additional surgical treatment. When multiple tumors are present, determining metastatic versus synchronous primary tumors is necessary for appropriate treatment. Identification can be achieved using allelotyping for loss of heterozygosity.
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James RD, Glynne-Jones R, Meadows HM, Cunningham D, Myint AS, Saunders MP, Maughan T, McDonald A, Essapen S, Leslie M, Falk S, Wilson C, Gollins S, Begum R, Ledermann J, Kadalayil L, Sebag-Montefiore D. Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2 × 2 factorial trial. Lancet Oncol 2013; 14:516-24. [PMID: 23578724 DOI: 10.1016/s1470-2045(13)70086-x] [Citation(s) in RCA: 517] [Impact Index Per Article: 43.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Chemoradiation became the standard of care for anal cancer after the ACT I trial. However, only two-thirds of patients achieved local control, with 5-year survival of 50%; therefore, better treatments are needed. We investigated whether replacing mitomycin with cisplatin in chemoradiation improves response, and whether maintenance chemotherapy after chemoradiation improves survival. METHODS In this 2 × 2 factorial trial, we enrolled patients with histologically confirmed squamous-cell carcinoma of the anus without metastatic disease from 59 centres in the UK. Patients were randomly assigned to one of four groups, to receive either mitomycin (12 mg/m(2) on day 1) or cisplatin (60 mg/m(2) on days 1 and 29), with fluorouracil (1000 mg/m(2) per day on days 1-4 and 29-32) and radiotherapy (50.4 Gy in 28 daily fractions); with or without two courses of maintenance chemotherapy (fluorouracil and cisplatin at weeks 11 and 14). The random allocation was generated by computer and patients assigned by telephone. Randomisation was done by minimisation and stratified by tumour site, T and N stage, sex, age, and renal function. Neither patients nor investigators were masked to assignment. Primary endpoints were complete response at 26 weeks and acute toxic effects (for chemoradiation), and progression-free survival (for maintenance). The primary analyses were done by intention to treat. This study is registered at controlled-trials.com, number 26715889. FINDINGS We enrolled 940 patients: 472 were assigned to mitomycin, of whom 246 were assigned to no maintenance, 226 to maintenance; 468 were assigned to cisplatin, of whom 246 were assigned to no maintenance, 222 to maintenance. Median follow-up was 5.1 years (IQR 3.9-6.9). 391 of 432 (90.5%) patients in the mitomycin group versus 386 of 431 (89.6%) in the cisplatin group had a complete response at 26 weeks (difference -0.9%, 95% CI -4.9 to 3.1; p=0.64). Overall, toxic effects were similar in each group (334/472 [71%] for mitomycin vs 337/468 [72%] for cisplatin). The most common grade 3-4 toxic effects were skin (228/472 [48%] vs 222/468 [47%]), pain (122/472 [26%] vs 135/468 [29%]), haematological (124/472 [26%] vs 73/468 [16%]), and gastrointestinal (75/472 [16%] vs 85/468 [18%]). 3-year progression-free survival was 74% (95% CI 69-77; maintenance) versus 73% (95% CI 68-77; no maintenance; hazard ratio 0.95, 95% CI 0.75-1.21; p=0.70). INTERPRETATION The results of our trial--the largest in anal cancer to date--show that fluorouracil and mitomycin with 50.4 Gy radiotherapy in 28 daily fractions should remain standard practice in the UK. FUNDING Cancer Research UK.
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La Gamma N, Nandakumar G. The management of gastrointestinal tract malignancies. Hosp Pract (1995) 2013; 41:7-15. [PMID: 23545755 DOI: 10.3810/hp.2013.04.1021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Surgery is the mainstay of treatment for many patients with malignancies of the gastrointestinal (GI) tract. The coordination of patient care and timing of surgical intervention require a multidisciplinary approach. It is not unusual for GI malignancies to be discovered in a hospital setting; patients with these malignancies are frequently admitted and discharged from nonsurgical services. Therefore, it is imperative that all physicians involved in the care of patients with GI malignancies have knowledge regarding the workup and surgical treatment of GI tract lesions. This article is a brief overview of the workup and surgical management of malignancies of the GI tract.
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Affiliation(s)
- Nicholas La Gamma
- Weill Cornell Medical College, New York Presbyterian Hospital/Weill Cornell Medical Center, New York, NY, USA.
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Abstract
PURPOSE The aim of this study was to evaluate long-term oncologic outcomes after concurrent chemoradiation treatment for anal cancer. MATERIALS AND METHODS Between January 1979 and December 2008, the records of 50 consecutive patients with anal cancer and who were treated by chemoradiation or radiation only with a curative intent were retrospectively reviewed. The oncologic outcomes and the risk factors for recurrence were analyzed. RESULTS Of the 50 patients, 49 underwent concurrent chemoradiation and one underwent radiation only. After these definitive treatments, 43 (86.0%) achieved a clinical complete response. During the median follow-up of 60 months (range: 2-202 months), the 5-year overall survival, disease-free survival, and locoregional recurrence-free survival were 84.2%, 72.7%, and 69.9%, respectively. Multivariate analysis revealed that the performance status (p=0.031) and a clinical complete response (p=0.039) were the independent predictors for overall survival; lymph node involvement (p=0.031) was the only independent predictor for disease-free survival. CONCLUSION The performance status and a clinical complete response may be reliable predictors of survival after chemoradiation for anal cancer. The addition of irradiation to the inguinal area may not be significantly associated with the outcomes.
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Affiliation(s)
- Hun Jin Kim
- Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, Jeollanam-do, Korea
| | - Jung Wook Huh
- Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, Jeollanam-do, Korea
| | - Chang Hyun Kim
- Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, Jeollanam-do, Korea
| | - Sang Woo Lim
- Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, Jeollanam-do, Korea
| | - Taek-Keun Nam
- Department of Radiation Oncology, Chonnam National University Hwasun Hospital and Medical School, Jeollanam-do, Korea
| | - Hyeong Rok Kim
- Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, Jeollanam-do, Korea
| | - Young Jin Kim
- Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, Jeollanam-do, Korea
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Radiotherapy with or without chemotherapy in the treatment of anal cancer: 20-year experience from a single institute. Strahlenther Onkol 2012; 189:18-25. [DOI: 10.1007/s00066-012-0236-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2012] [Accepted: 09/17/2012] [Indexed: 01/29/2023]
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Cacheux W, Lievre A, De La Rochefordiere A, Dieumegard B, Cvitkovic F, Labib A, Mitry E, Buecher B. Chemotherapy in the treatment of anal canal carcinoma. Dig Liver Dis 2012; 44:803-11. [PMID: 22658644 DOI: 10.1016/j.dld.2012.04.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2012] [Accepted: 04/18/2012] [Indexed: 12/11/2022]
Abstract
Squamous cell carcinomas of the anal canal are generally diagnosed at a localized or locally advanced stage and only 5% are metastatic at the time of diagnosis. Advanced forms are therefore much rarer than localized forms and usually correspond to metachronous metastases of initially localized disease. Systemic chemotherapy is indicated for the treatment of both localized disease, in combination with radiotherapy, and metastatic disease. The purpose of this article is to define the current indications and modalities of chemotherapy in the treatment of these cancers based on a review of the published data and in the light of available guidelines.
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Affiliation(s)
- Wulfran Cacheux
- Department of Medical Oncology, Groupe Hospitalier, Institut Curie, 26 rue d'Ulm, 75248 Paris Cédex 5, France
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Three cytotoxic drugs combined with pelvic radiation and as maintenance chemotherapy for patients with squamous cell carcinoma of the anus (SCCA): Long-term follow-up of a phase II pilot study using 5-fluorouracil, mitomycin C and cisplatin. Radiother Oncol 2012; 104:155-60. [DOI: 10.1016/j.radonc.2012.06.006] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2011] [Revised: 05/26/2012] [Accepted: 06/10/2012] [Indexed: 11/20/2022]
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Satake H, Yoshino T, Sasaki T, Bando H, Yoda Y, Ikematsu H, Kojima T, Fuse N, Zenda S, Doi T, Kaneko K, Ohtsu A. Early clinical outcomes of anal squamous cell carcinoma treated with concurrent chemoradiotherapy with 5-Fluorouracil plus mitomycin C in Japanese patients: experience at a single institution. Jpn J Clin Oncol 2012; 42:861-4. [PMID: 22717459 DOI: 10.1093/jjco/hys093] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Concurrent chemoradiotherapy with 5-fluorouracil plus mitomycin C has been established as a standard therapy for non-metastatic anal squamous cell carcinoma in the West. However, there have been few reports of chemoradiotherapy for anal squamous cell carcinoma in Japan. We retrospectively investigated seven consecutive anal squamous cell carcinoma patients who were treated with concurrent chemoradiotherapy consisting of 5-fluorouracil plus mitomycin C with a total irradiation of 59.4 Gy. The patients consisted of two males and five females. Clinical stages II/IIIA/IIIB accounted for four, one and two patients, respectively. Full-dose irradiation was completed in all patients. Median relative dose intensities of 5-fluorouracil and mitomycin C were both 99%. All patients achieved complete response. At a median follow-up of 37.5 months, one patient experienced local recurrence. The most common grade 3/4 acute toxicities were dermatitis in 100% and anal pain in 71%. There was no treatment-related death. Concurrent chemoradiotherapy appears to be tolerable and effective in Japanese patients with anal squamous cell carcinoma.
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Affiliation(s)
- Hironaga Satake
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa 277-8577, Japan
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Oblak I, Petric P, Anderluh F, Velenik V, Fras PA. Long term outcome after combined modality treatment for anal cancer. Radiol Oncol 2012; 46:145-52. [PMID: 23077451 PMCID: PMC3472931 DOI: 10.2478/v10019-012-0022-2] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2011] [Accepted: 01/25/2012] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND The aim of the retrospective study was to evaluate the effectiveness and toxicity of radiochemotherapy in patients with squamous cell carcinoma of the anal canal treated at a single institution. PATIENTS AND METHODS Between 1/2003 and 9/2010, 84 patients were treated with radical radiochemotherapy at the Institute of Oncology Ljubljana, Slovenia. The treatment consisted of 3-dimensional conformal external beam radiotherapy with concurrent chemotherapy (5-fluorouracil and mytomycin C), followed by brachytherapy or external beam boost. The toxicity of therapy and its effectiveness were assessed. RESULTS The treatment was completed according to the protocol in 79.8% of patients. The median follow-up time of 55 survivors was 53 months (range: 16-105 months). The 5-year locoregional control (LRC), disease-free survival (DFS), disease-specific survival (DSS), overall survival (OS) and colostomy-free survival (CFS) rates were 71%, 68%, 81%, 67% and 85%, respectively. No treatment-related mortality was observed. The most frequent acute side-effect of the treatment was radiodermatitis (grade 3-4 in 58.2% of patients). LENT-SOMA grade 3-4 late radiation side effects were observed in 15 (18%) patients. In patients with brachytherapy boost a trend of less late side effects was observed compared to patients with external beam boost (P=0.066). On multivariate analysis, complete clinical disease response was identified as an independent prognostic factor for LRC, DFS and DSS, the salvage surgery for LRC and DFS, whereas Hb below 120 g/l retained its independent prognostic value for OS. CONCLUSIONS Radiochemotherapy provides an excellent disease control and the survival with preserving anal sphincter function in majority of patients. Surgical salvage with abdominoperineal resection for persistent or recurrent disease has curative potential.
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Affiliation(s)
- Irena Oblak
- Department of Radiotherapy, Institute of Oncology Ljubljana, Ljubljana, Slovenia
| | - Primoz Petric
- Department of Radiotherapy, Institute of Oncology Ljubljana, Ljubljana, Slovenia
| | - Franc Anderluh
- Department of Radiotherapy, Institute of Oncology Ljubljana, Ljubljana, Slovenia
| | - Vaneja Velenik
- Department of Radiotherapy, Institute of Oncology Ljubljana, Ljubljana, Slovenia
| | - Peter Albert Fras
- Department of Radiotherapy, Institute of Oncology Ljubljana, Ljubljana, Slovenia
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Peiffert D, Tournier-Rangeard L, Gérard JP, Lemanski C, François E, Giovannini M, Cvitkovic F, Mirabel X, Bouché O, Luporsi E, Conroy T, Montoto-Grillot C, Mornex F, Lusinchi A, Hannoun-Lévi JM, Seitz JF, Adenis A, Hennequin C, Denis B, Ducreux M. Induction chemotherapy and dose intensification of the radiation boost in locally advanced anal canal carcinoma: final analysis of the randomized UNICANCER ACCORD 03 trial. J Clin Oncol 2012; 30:1941-8. [PMID: 22529257 DOI: 10.1200/jco.2011.35.4837] [Citation(s) in RCA: 258] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
PURPOSE Concomitant radiochemotherapy (RCT) is the standard for locally advanced anal canal carcinoma (LAACC). Questions regarding the role of induction chemotherapy (ICT) and a higher radiation dose in LAACC are pending. Our trial was designed to determine whether dose escalation of the radiation boost or two cycles of ICT before concomitant RCT lead to an improvement in colostomy-free survival (CFS). PATIENTS AND METHODS Patients with tumors ≥ 40 mm, or < 40 mm and N1-3M0 were randomly assigned to one of four treatment arms: (A) two ICT cycles (fluorouracil 800 mg/m(2)/d intravenous [IV] infusion, days 1 through 4 and 29 to 32; and cisplatin 80 mg/m(2) IV, on days 1 and 29), RCT (45 Gy in 25 fractions over 5 weeks, fluorouracil and cisplatin during weeks 1 and 5), and standard-dose boost (SD; 15 Gy); (B) two ICT cycles, RCT, and high-dose boost (HD; 20-25 Gy); (C): RCT and SD boost (reference arm); and (D) RCT and HD boost. RESULTS Two hundred eighty-three of 307 patients achieved full treatment. With a median follow-up period of 50 months, the 5-year CFS rates were 69.6%, 82.4%, 77.1%, and 72.7% in arms A, B, C, and D, respectively. Considering the 2 × 2 factorial analysis, the 5-year CFS was 76.5% versus 75.0% (P = .37) in groups A and B versus C and D, respectively (ICT effect), and 73.7% versus 77.8% in groups A and C versus B and D, respectively (RT-dose effect; P = .067). CONCLUSION Using CFS as our main end point, we did not find an advantage for either ICT or HD radiation boost in LAACC. Nevertheless, the results of the most treatment-intense arm B should prompt the design of further intensification studies.
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Affiliation(s)
- Didier Peiffert
- EA 4360Centre, Alexis Vautrin and Nancy University,Vandoeuvre-lès-Nancy, France.
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Chakravarthy AB, Catalano PJ, Martenson JA, Mondschein JK, Wagner H, Mansour EG, Talamonti MS, Benson AB. Long-term follow-up of a Phase II trial of high-dose radiation with concurrent 5-fluorouracil and cisplatin in patients with anal cancer (ECOG E4292). Int J Radiat Oncol Biol Phys 2011; 81:e607-13. [PMID: 21514072 PMCID: PMC3197794 DOI: 10.1016/j.ijrobp.2011.02.042] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2010] [Revised: 01/31/2011] [Accepted: 02/11/2011] [Indexed: 10/18/2022]
Abstract
PURPOSE Although chemoradiation using 5-fluorouracil (5-FU) and mitomycin-C (MMC) is the standard of care in the treatment of anal cancer, many patients are unable to tolerate MMC. This Phase II clinical trial was performed to determine whether cisplatin could replace MMC in the treatment of anal cancer. METHODS AND MATERIALS Thirty-three patients with localized anal cancer were enrolled. One patient registered but never received any assigned therapy and was excluded from all analyses. Between February 1, 1993, and July 21, 1993, 19 patients were accrued to Cohort 1. Radiation consisted of 45 Gy to the primary tumor and pelvic nodes, followed by a boost to the primary and involved nodes to 59.4 Gy. A planned 2-week treatment break was used after 36 Gy. Concurrent chemotherapy consisted of 5-FU 1,000 mg/m(2)/day on Days 1 to 4 and cisplatin 75 mg/m(2) on Day 1. A second course of 5-FU and cisplatin was given after 36 Gy, when the patient resumed radiation therapy. Between April 4, 1996, and September 23, 1996, an additional 13 patients (Cohort 2) were accrued to the study and received the same treatment except without the planned treatment break. RESULTS Complete response was seen in 78% (90% CI, 63-89) of patients and was higher in patients who did not get a planned treatment break (92% vs. 68%). The overall Grade 4 toxicity rate was 31%. One treatment-related death (Grade 5) occurred in a patient who developed sepsis. The 5-year overall survival was 69%. CONCLUSIONS Radiation therapy, cisplatin, and 5-FU resulted in an overall objective response (complete response + partial response) of 97%. Although the 5-year progression-free survival was only 55%, the overall 5-year survival was 69%. Given the excellent salvage provided by surgery, this study affirms that cisplatin-based regimens may be an alternative for patients who cannot tolerate the severe hematologic toxicities associated with mitomycin-based chemoradiation regimens.
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Affiliation(s)
- A Bapsi Chakravarthy
- Department of Radiation Oncology, Vanderbilt University Medical Center, 2220 Pierce Avenue, Preston Research Building, Room B-1003, Nashville, TN 37232, USA.
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Twenty-year experience in the management of squamous cell anal canal carcinoma with interstitial brachytherapy. Clin Transl Oncol 2011; 13:472-9. [PMID: 21775274 DOI: 10.1007/s12094-011-0684-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
OBJECTIVES The aim of this study was to retrospectively evaluate clinical characteristics, local control, acute and late toxicity, and prognostic factors of patients with anal canal carcinoma treated with brachytherapy. METHODS From 1989 to 2009, 38 patients were treated with iridium 192 low-dose-rate (N = 26) or pulsed-dose-rate (N = 12) interstitial brachytherapy at a single institution. The median age was 62 years (range, 38-86 years). The TNM classification was as follows: 10 T1, 22 T2, 5 T3 and 1 T4; 32 N0, 3 N1 and 3 N2. Most patients (32/38) received either a first course of radiochemotherapy (N = 22) or radiotherapy alone (N=10) consisting of a total delivered dose of 45 Gy to the pelvis (range, 32-50) followed by a boost a median of 18 days later of 15-35 Gy (median 20 Gy) to the anal canal. The remaining 6 cases were treated with brachytherapy alone (dose range, 60-65 Gy). RESULTS With a median follow-up of 30 months (range, 4-200), 2- and 5-year local control rates were 91% and 87%, respectively. Preservation of the anal sphincter was achieved in 32 patients (84%). Three patients experienced incontinence after brachytherapy. Only 2 patients showed chronic mucositis grade 3/4. Age proved to be a statistically significant prognostic factor for overall survival in the univariate (p = 0.033) and multivariate analyses (p = 0.018). Concurrent chemotherapy with external beam radiotherapy was a statistically significant prognostic factor for disease-free survival in the univariate and multivariate analyses (p = 0.007 and p = 0.044, respectively). CONCLUSIONS Interstitial brachytherapy appears to be an effective and well tolerated treatment for anal carcinoma offering both high local tumour control and anal sphincter preservation.
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Lim F, Glynne-Jones R. Chemotherapy/chemoradiation in anal cancer: A systematic review. Cancer Treat Rev 2011; 37:520-32. [DOI: 10.1016/j.ctrv.2011.02.003] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2010] [Revised: 02/07/2011] [Accepted: 02/27/2011] [Indexed: 12/27/2022]
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Eeson G, Foo M, Harrow S, McGregor G, Hay J. Outcomes of salvage surgery for epidermoid carcinoma of the anus following failed combined modality treatment. Am J Surg 2011; 201:628-33. [PMID: 21545912 DOI: 10.1016/j.amjsurg.2011.01.015] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2010] [Revised: 01/25/2011] [Accepted: 01/25/2011] [Indexed: 12/21/2022]
Abstract
BACKGROUND Chemoradiation is first-line therapy for epidermoid carcinoma of the anus (ECA). Surgery is reserved for treatment failures. The authors report outcomes after salvage procedures for ECA. METHODS All treatment failures managed with radical surgery between 1998 and 2006 in our institution were reviewed. The Kaplan-Meier method was used for survival analysis. Log-rank and Cox regression were used for univariate and multivariate analysis, respectively. RESULTS Fifty-one patients underwent salvage abdominoperineal resection for locoregional failure. Five-year overall survival after abdominoperineal resection was 29% (median, 22 months). Age, gender, human immunodeficiency virus status, tumor-node-metastasis stage, node status, and failure type did not predict survival. Negative resection margin was most strongly associated with improved overall and disease-free survival (P = .03 and P < .0001, respectively). Median survival for patients undergoing inguinal lymph node dissection for regional recurrence (n = 6) was 11 months, with freedom from cancer achieved in 2 of 6 patients. CONCLUSIONS Recurrent anal carcinoma after primary chemoradiotherapy carries a poor prognosis. Salvage abdominoperineal resection offers a potential for long-term survival.
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Affiliation(s)
- Gareth Eeson
- Division of General Surgery, University of British Columbia, Vancouver, BC, Canada.
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Ortholan C, Resbeut M, Hannoun-Levi JM, Teissier E, Gerard JP, Ronchin P, Zaccariotto A, Minsat M, Benezery K, François E, Salem N, Ellis S, Azria D, Champetier C, Gross E, Cowen D. Anal canal cancer: management of inguinal nodes and benefit of prophylactic inguinal irradiation (CORS-03 Study). Int J Radiat Oncol Biol Phys 2011; 82:1988-95. [PMID: 21570207 DOI: 10.1016/j.ijrobp.2011.02.010] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2010] [Revised: 01/16/2011] [Accepted: 02/09/2011] [Indexed: 11/29/2022]
Abstract
PURPOSE To evaluate the benefit of prophylactic inguinal irradiation (PII) in anal canal squamous cell carcinoma (ASCC). METHODS AND MATERIALS This retrospective study analyzed the outcome of 208 patients presenting with ASCC treated between 2000 and 2004 in four cancer centers of the south of France. RESULTS The population study included 35 T1, 86 T2, 59 T3, 20 T4, and 8 T stage unknown patients. Twenty-seven patients presented with macroscopic inguinal node involvement. Of the 181 patients with uninvolved nodes at presentation, 75 received a PII to a total dose of 45-50 Gy (PII group) and 106 did not receive PII (no PII group). Compared with the no PII group, patients in the PII group were younger (60% vs. 41% of patients age <68 years, p = 0.01) and had larger tumor (T3-4 = 46% vs. 27% p = 0.01). The other characteristics were well balanced between the two groups. Median follow-up was 61 months. Fourteen patients in the no PII group vs. 1 patient in the PII group developed inguinal recurrence. The 5-year cumulative rate of inguinal recurrence (CRIR) was 2% and 16% in PII and no PII group respectively (p = 0.006). In the no PII group, the 5-year CRIR was 12% and 30% for T1-T2 and T3-T4 respectively (p = 0.02). Overall survival, disease-specific survival, and disease-free survival were similar between the two groups. In the PII group, no Grade >2 toxicity of the lower extremity was observed. CONCLUSION PII with a dose of 45 Gy is safe and highly efficient to prevent inguinal recurrence and should be recommended for all T3-4 tumors. For early-stage tumors, PII should also be discussed, because the 5-year inguinal recurrence risk remains substantial when omitting PII (about 10%).
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Affiliation(s)
- Cécile Ortholan
- Department of Radiation Therapy, Antoine Lacassagne Cancer Center, Nice, France.
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[Carcinoma of the anal canal: state of art, issues in geriatric oncology and molecular targeted therapies]. Bull Cancer 2011; 98:146-53. [PMID: 21382795 DOI: 10.1684/bdc.2011.1305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Since the 1990, chemoradiation has become the standard treatment for locally advanced anal cancer. Recent progress in molecular biology and the growing number of elderly patients invite the clinicians to personalize the multimodal therapy strategy. However, data about anal cancer and elderly patients or targeted therapy are extremely sparse. Indeed, national or international guidelines don't mention these two subjects. The purpose of this article is to make the state of art of the management of anal cancer and its interferences with geriatrics and molecular targeted therapy.
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Zampino MG, Magni E, Leonardi MC, Santoro L, Petazzi E, Fodor C, Petralia G, Trovato C, Nolè F, Orecchia R. Concurrent cisplatin, continuous infusion fluorouracil and radiotherapy followed by tailored consolidation treatment in non metastatic anal squamous cell carcinoma. BMC Cancer 2011; 11:55. [PMID: 21291546 PMCID: PMC3055231 DOI: 10.1186/1471-2407-11-55] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2010] [Accepted: 02/03/2011] [Indexed: 12/15/2022] Open
Abstract
Background To evaluate efficacy and feasibility of chemo-radiotherapy in patients with non-metastatic anal squamous-cell-cancer. Methods TNM staged anal squamous-cell cancer patients were treated with pelvic radiotherapy concomitant to continuous infusion fluorouracil plus cisplatin for at least 2 cycles. In T3-T4 or any T - N+ tumours or in "slow-responder" cases, 1-2 chemotherapy courses were subsequently administered. Tumour assessment was performed at baseline and 6-8 weeks after radiotherapy to evaluate response. Results 29 patients were enrolled: 4 males, 25 females; median age 57 years; baseline T1/T2/T3/T4 2/12/7/8; N involvement 17. Median dose pelvic radiotherapy was 59.4 Gy (range: 54-74). In 5 patients 2 chemotherapy courses, in 12 patients three and in 12 patients four courses were performed. At first evaluation, 27 CR (93.1%; 95% CI: 78% - 98%) and 2 SD were observed. Main grade (G) 3 toxic events were neutropenia (8%), diarrhoea (8%) and dermatitis (62%). Most frequent late events G3-G4 occurred in 14 patients: proctitis (5), dermatitis (4), bladder dysfunctions (2), sexual dysfunctions (9), lower extremity venous thromboses (2), dysuria (1), stenosis (1) and tenesmus (1). Five patients reported G1 leucopoenia. The rate of colostomy was 14%. After a median follow up of 42 months (range: 4-81), 20 patients are still alive without relapse and 3 died due to PD. The estimated 7-year DFS was 83.4% (C.I.: 68.3%-98.5%) and the estimated 7-year OS was 85.7% (C.I.: 70% - 100%). The 1-year and the estimated 7-year colostomy-free survivals were 85.9% (C.I.: 73.1% - 98.7%). Conclusions Concurrent cisplatin plus fluorouracil and radiotherapy is associated with favourable local control rates and acute toxicity. Future investigations will be directed towards research into molecular biomarkers related to disease progression and resistance to chemo-radiotherapy and to the evaluation of new cytotoxic agents or targeted drugs, such as anti-epidermal growth factor receptor, concomitant to RT and to determining the role of intensity-modulated radiotherapy.
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Affiliation(s)
- Maria G Zampino
- Medical Care Unit, Department of Medicine, European Institute of Oncology, via Ripamonti 435, Milan 20141, Italy.
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Renehan AG, O'Dwyer ST. Initial management through the anal cancer multidisciplinary team meeting. Colorectal Dis 2011; 13 Suppl 1:21-8. [PMID: 21251169 DOI: 10.1111/j.1463-1318.2010.02495.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- A G Renehan
- Department of Surgery, Christie NHS Foundation Trust, Manchester, UK.
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Mitomycin-C– or Cisplatin-Based Chemoradiotherapy for Anal Canal Carcinoma: Long-Term Results. Int J Radiat Oncol Biol Phys 2011; 79:490-5. [DOI: 10.1016/j.ijrobp.2009.11.057] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2009] [Revised: 11/12/2009] [Accepted: 11/12/2009] [Indexed: 11/19/2022]
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Matthews JHL, Burmeister BH, Borg M, Capp AL, Joseph D, Thompson KM, Thompson PI, Harvey JA, Spry NA. T1-2 anal carcinoma requires elective inguinal radiation treatment--the results of Trans Tasman Radiation Oncology Group study TROG 99.02. Radiother Oncol 2010; 98:93-8. [PMID: 21109321 DOI: 10.1016/j.radonc.2010.10.005] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2010] [Revised: 09/27/2010] [Accepted: 10/03/2010] [Indexed: 11/18/2022]
Abstract
BACKGROUND AND PURPOSE Elective inguinal irradiation increases morbidity. We describe outcomes of moderate intensity chemoradiation treating anal canal and adjacent pelvic nodes only. MATERIAL AND METHODS Forty patients with T1-2, N0 anal carcinoma were enrolled between March 1999 and March 2003. Inguinal nodes were NOT electively irradiated. The anal canal and regional pelvic nodes received 36 Gy/20# over 4 weeks, and 2 weeks later the anal canal was boosted with 14.4 Gy/8#. Chemotherapy was 5 fluorouracil 800 mg/m(2)/day on days 1-4 and 36-39, and Mitomycin C 10mg/m(2) on day 1. RESULTS Median follow-up was 44 months. Complete response was 95%. Four year results were; overall survival 71%, local control 82%, and colostomy-free survival (including salvage) 85%. Inguinal failure occurred in 22.5% but was isolated in only 12.5%. Treatment was well tolerated acutely with no toxic deaths. Severe late toxicity occurred in 7.5%. CONCLUSIONS This moderate dose 'non inguinal' chemoradiation regimen resulted in modest acute toxicity, minimal long term morbidity and local control in line with other series. However staging failed to identify 12.5% of patients whose isolated inguinal failure might have been prevented by elective irradiation. Without more effective staging, all patients should receive elective inguinal irradiation.
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Affiliation(s)
- John H L Matthews
- Department of Radiation Oncology, Auckland City Hospital, New Zealand.
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