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Valadão M, Riechelmann RP, Silva JACE, Mali J, Azevedo B, Aguiar S, Araújo R, Feitoza M, Coelho E, Rosa AA, Jay N, Braun AC, Pinheiro R, Salvador H. Brazilian Society of Surgical Oncology: Guidelines for the management of anal canal cancer. J Surg Oncol 2024; 130:810-829. [PMID: 37021640 DOI: 10.1002/jso.27269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Accepted: 03/20/2023] [Indexed: 04/07/2023]
Abstract
BACKGROUND Anal canal squamous cell carcinoma (SCC) is a relatively uncommon neoplasia, and it is mostly a local-regional cancer, of low metastatic potential (only 15%), resulting in cure in most cases treated with definitive chemoradiation. On the other hand, its incidence has been steadily increasing over the last decades, which makes it an important public health problem. In an effort to provide surgeons and oncologists who treat patients with anal cancer with the most updated information based on the best scientific evidence, the Brazilian Society of Surgical Oncology (SBCO) has produced the present guideline for the management of anal canal SCC, focused on the main topics related to daily clinical practice. OBJECTIVES The SBCO developed the present guidelines to provide recommendations on the main topics related to the management of anal canal squamous cell carcinoma (SCC) based on current scientific evidence. METHODS Between October 2022 and January 2023, 14 experts met to develop the guidelines for the management of anal canal cancer. A total of 30 relevant topics were distributed among the participants. The methodological quality of a final list with 121 sources was evaluated, all the evidence was examined and revised, and the management guidelines were formulated by the 14-expert committee. To reach a final consensus, all the topics were reviewed in a meeting that was attended by all the experts. RESULTS The proposed guidelines contained 30 topics considered to be highly relevant in the management of anal canal cancer, covering subjects related to screening recommendations, preventive measures, tests required for diagnosing and staging, treatment strategies, response assessment after chemoradiotherapy, surgical technique-related aspects, and follow-up recommendations. In addition, screening and response assessment algorithms, and a checklist were proposed to summarize the important information and offer an updated tool to assist surgeons and oncologists who treat anal canal cancer and in providing the best care to their patients. CONCLUSION These guidelines summarize recommendations based on the most current scientific evidence on relevant aspects of anal canal cancer management and are a practical guide to help surgeons and oncologists who treat anal canal cancer make the best therapeutic decisions.
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Affiliation(s)
- Marcus Valadão
- Department of Abdomino-Pelvic Surgery, Instituto Nacional de Cancer, Rio de Janeiro, Brazil
| | | | | | - Jorge Mali
- Department of Surgery, Hospital do Câncer de Londrina, Londrina, Brazil
| | - Bruno Azevedo
- Department of Surgical Oncology, Grupo Oncoclínicas, Curitiba, Brazil
| | - Samuel Aguiar
- Department of Surgical Oncology, AC Camargo Cancer, CenterSão Paulo, Brazil
| | - Rodrigo Araújo
- Department of Abdomino-Pelvic Surgery, Instituto Nacional de Cancer, Rio de Janeiro, Brazil
| | - Mario Feitoza
- Brazilian Society of Surgical Oncology, Rio de Janeiro, Brazil
| | - Eid Coelho
- Department of Surgery, Hospital São Marcos, Teresina, Brazil
| | - Arthur Accioly Rosa
- Department of Radiation Oncology, Oncoclinicas Salvador-Hospital Santa Izabel, Salvador, Brazil
| | - Naomi Jay
- San Francisco School of Medicine, University of California, San Francisco, California, USA
| | | | - Rodrigo Pinheiro
- Department of Surgical Oncology, Hospital de Base do Distrito Federal, Brasilia, Brazil
| | - Héber Salvador
- Department of Surgical Oncology, AC Camargo Cancer, CenterSão Paulo, Brazil
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Rosen R, Quezada-Diaz FF, Gönen M, Karagkounis G, Widmar M, Wei IH, Smith JJ, Nash GM, Weiser MR, Paty PB, Cercek A, Romesser PB, Sanchez-Vega F, Adileh M, Roth O’Brien D, Hajj C, Williams VM, Shcherba M, Gu P, Crane C, Saltz LB, Garcia Aguilar J, Pappou E. Oncologic Outcomes of Salvage Abdominoperineal Resection for Anal Squamous Cell Carcinoma Initially Managed with Chemoradiation. J Clin Med 2024; 13:2156. [PMID: 38673429 PMCID: PMC11050212 DOI: 10.3390/jcm13082156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2024] [Revised: 04/01/2024] [Accepted: 04/03/2024] [Indexed: 04/28/2024] Open
Abstract
Background: Abdominoperineal resection (APR) has been advocated for persistent or recurrent disease after failure of chemoradiation (CRT) for anal squamous cell cancer (SCC). Treatment with salvage APR can potentially achieve a cure. This study aimed to analyze oncological outcomes for salvage APR in a recent time period at a comprehensive cancer center. Methods: A retrospective review of all patients who underwent APR for biopsy-proven persistent or recurrent anal SCC between 1 January 2007 and 31 December 2020 was performed. Patients with stage IV disease at the time of initial diagnosis and patients with missing data were excluded. Univariate analysis was used with a chi-square test for categorical variables, and non-parametric tests were used for continuous variables. Kaplan-Meier survival analysis was performed to evaluate disease-specific (DSS), post-APR local recurrence-free (RFS), and disease-free survival (DFS). Results: A total of 96 patients were included in the analysis: 39 (41%) with persistent disease and 57 (59%) with recurrent SCC after chemoradiation had been completed. The median follow-up was 22 months (IQR 11-47). Forty-nine patients (51%) underwent extended APR and/or pelvic exenteration. Eight (8%) patients developed local recurrence, 30 (31%) developed local and distant recurrences, and 16 (17%) developed distant recurrences alone. The 3-year DSS, post-APR local recurrence-free survival, and disease-free survival were 53.8% (95% CI 43.5-66.5%), 54.5% (95% CI 44.4-66.8%), and 26.8% (95% CI 18.6-38.7%), respectively. In multivariate logistic regression analysis, positive microscopic margin (OR 10.0, 95% CI 2.16-46.12, p = 0.003), positive nodes in the surgical specimen (OR 9.19, 95% CI 1.99-42.52, p = 0.005), and lymphovascular invasion (OR 2.61 95% CI 1.05-6.51, p = 0.04) were associated with recurrence of disease. Gender, indication for APR (recurrent vs. persistent disease), HIV status, extent of surgery, or type of reconstruction did not influence survival outcomes. Twenty patients had targeted tumor-sequencing data available. Nine patients had PIK3CA mutations, seven of whom experienced a recurrence. Conclusions: Salvage APR for anal SCC after failed CRT was associated with poor disease-specific survival and low recurrence-free survival. Anal SCC patients undergoing salvage APR should be counseled that microscopic positive margins, positive lymph nodes, or the presence of lymphovascular invasion in the APR specimen are prognosticators for disease relapse. Our results accentuate the necessity for additional treatment strategies for the ongoing treatment challenge of persistent or recurrent anal SCC after failed CRT.
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Affiliation(s)
- Roni Rosen
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (F.F.Q.-D.); (J.J.S.)
| | - Felipe F. Quezada-Diaz
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (F.F.Q.-D.); (J.J.S.)
| | - Mithat Gönen
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Georgios Karagkounis
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (F.F.Q.-D.); (J.J.S.)
| | - Maria Widmar
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (F.F.Q.-D.); (J.J.S.)
| | - Iris H. Wei
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (F.F.Q.-D.); (J.J.S.)
| | - J. Joshua Smith
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (F.F.Q.-D.); (J.J.S.)
| | - Garrett M. Nash
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (F.F.Q.-D.); (J.J.S.)
| | - Martin R. Weiser
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (F.F.Q.-D.); (J.J.S.)
| | - Philip B. Paty
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (F.F.Q.-D.); (J.J.S.)
| | - Andrea Cercek
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (P.G.)
| | - Paul B. Romesser
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (P.B.R.)
| | - Francisco Sanchez-Vega
- Department of Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Mohammad Adileh
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (F.F.Q.-D.); (J.J.S.)
| | - Diana Roth O’Brien
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (P.B.R.)
| | - Carla Hajj
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (P.B.R.)
| | - Vonetta M. Williams
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (P.B.R.)
| | - Marina Shcherba
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (P.G.)
| | - Ping Gu
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (P.G.)
| | - Christopher Crane
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (P.B.R.)
| | - Leonard B. Saltz
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (P.G.)
| | - Julio Garcia Aguilar
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (F.F.Q.-D.); (J.J.S.)
| | - Emmanouil Pappou
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA (F.F.Q.-D.); (J.J.S.)
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Damron EP, McDonald J, Rooney MK, Das P, Ludmir EB, Minsky BD, Messick C, Chang GJ, Morris VK, Holliday EB. Salvage Treatment of Recurrent or Persistent Anal Squamous Cell Carcinoma: The Role of Multi-modality Therapy. Clin Colorectal Cancer 2024; 23:85-94. [PMID: 38216367 PMCID: PMC11874619 DOI: 10.1016/j.clcc.2023.12.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 12/07/2023] [Accepted: 12/10/2023] [Indexed: 01/14/2024]
Abstract
BACKGROUND The standard treatment for recurrent or persistent anal squamous cell carcinoma is surgical salvage, but disease control and survival are suboptimal. PATIENTS/METHODS Patients treated for recurrent or persistent anal squamous cell carcinoma at our institution from 2002 to 2022 were included. Patients were classified by type of salvage treatment received: surgery alone vs. reirradiation followed by surgery and by whether they received intraoperative radiation at the time of surgery. Clinical and pathologic variables were collected and assessed for association with risk of second local recurrence and death from any cause. RESULTS Sixty four patients were included; 55(85.9%) were treated with surgery alone and 9 (14.1%) were treated with reirradiation followed by surgery. Median (IQR) follow up from the time of salvage treatment was 40.0 (20.3-68.0) months. The 3-year cumulative incidence of second local recurrence (95% CI) after salvage surgery was 36% (24%-48%); 39% (26%-52%) for patients treated with surgery alone and 15% (0.46%-51%) for patients treated with reirradiation followed by surgery. Factors associated with increased second local recurrence after salvage surgery included a locoregional recurrence, lymphovascular space invasion and positive surgical margins. The 3-year overall survival (95% CI) after salvage surgery was 70% (59%-83%); 68% (7%-56%) after surgery alone and 89% (10.5%-70.6%) after reirradiation followed by surgery. Factors associated with worse overall survival included male sex, a larger recurrent tumor and positive surgical margins. CONCLUSIONS Approximately 60% of patients achieved pelvic control after salvage therapy for recurrent or persistent anal squamous cell carcinoma. Although receipt of reirradiation and intraoperative radiation were not associated with improved second local recurrence or overall survival in our cohort, patients with positive surgical margins and lymphovascular space invasion on surgical pathology had higher rates of pelvic recurrence after salvage surgery and may benefit from escalated salvage therapy.
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Affiliation(s)
- Ethan P Damron
- University of Texas McGovern Medical School, Houston, TX
| | - Jordan McDonald
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | | | - Prajnan Das
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Ethan B Ludmir
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Bruce D Minsky
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Craig Messick
- Department of Colorectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - George J Chang
- Department of Colorectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Van K Morris
- Deparment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Emma B Holliday
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
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Brown KGM, Solomon MJ, Steffens D, Ng KS, Byrne CM, Austin KKS, Lee PJ. Pelvic Exenteration for Squamous Cell Carcinoma of the Anus: Oncological, Morbidity, and Quality-of-Life Outcomes. Dis Colon Rectum 2023; 66:1427-1434. [PMID: 37493254 DOI: 10.1097/dcr.0000000000002919] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/27/2023]
Abstract
BACKGROUND Salvage surgery is the only potentially curative treatment option for recurrent squamous cell carcinoma of the anus. Where adjacent pelvic viscera, soft tissues, and bone are involved, pelvic exenteration with a wide perineal excision may be required to ensure clear surgical margins and increase the likelihood of long-term survival. OBJECTIVE To report oncological, morbidity, and quality-of-life outcomes of pelvic exenteration for anal squamous cell carcinoma. DESIGN Cohort study with retrospective analysis of prospectively collected data. SETTINGS This study was conducted at a high-volume pelvic exenteration center. PATIENTS Those who underwent pelvic exenteration for anal squamous cell carcinoma between 1994 and 2022. MAIN OUTCOME MEASURES Local recurrence-free and overall survival, intraoperative and postoperative complication rates, R0 resection rate, and long-term quality-of-life outcomes. RESULTS Of 958 patients who underwent pelvic exenteration, 66 (6.9%) had anal squamous cell carcinoma. Thirty-two patients (48.5%) were male and the median age was 57 years (range, 31-79). Ten patients (15%) had primary anal squamous cell carcinoma, 49 (74%) had a recurrent tumor, and 7 (11%) had a re-recurrent tumor. Twenty-two patients (33%) and 16 patients (24%) had a major complication and unplanned return to the operating theater, respectively. Of the 62 patients who underwent pelvic exenteration with curative intent, 50 (81%) had R0 resection, and the 5-year overall and local recurrence-free survival rates were 41% and 37%, respectively. R0 resection was associated with a higher 5-year overall survival (50% vs 8%, p < 0.001). The mental health component scores and several individual quality-of-life domains presented improved trajectories postoperatively (all p values <0.05). LIMITATIONS The generalizability of the findings outside specialist pelvic exenteration centers may be limited. CONCLUSIONS Morbidity, long-term survival, and quality-of-life outcomes after pelvic exenteration for anal squamous cell carcinoma are comparable to published outcomes of pelvic exenteration for other tumor types. EXENTERACIN PLVICA POR CARCINOMA EPIDERMOIDE DE ANO RESULTADOS ONCOLGICOS, DE MORBILIDAD Y DE CALIDAD DE VIDA ANTECEDENTES:La cirugía de rescate es la única opción de tratamiento potencialmente curativa para el carcinoma de células escamosas del ano recurrente. Cuando están involucradas vísceras pélvicas, tejidos blandos y huesos adyacentes, puede ser necesaria una exenteración pélvica con una escisión perineal amplia para asegurar márgenes quirúrgicos claros y aumentar la probabilidad de supervivencia a largo plazo.OBJETIVO:Informar sobre los resultados oncológicos, de morbilidad y de calidad de vida de la exenteración pélvica por carcinoma anal de células escamosas.DISEÑO:Estudio de cohortes con análisis retrospectivo de datos recogidos prospectivamente.ENTORNO CLINICO:Este estudio se realizó en un centro de exenteración pélvica de alto volumen.PACIENTES:Aquellos que se sometieron a exenteración pélvica por carcinoma anal de células escamosas entre 1994 y 2022.PRINCIPALES MEDIDAS DE VALORACIÓN:Supervivencia global y libre de recidiva local, tasas de complicaciones intraoperatorias y posoperatorias, tasa de resección R0 y resultados de calidad de vida a largo plazo.RESULTADOS:De 958 pacientes que se sometieron a exenteración pélvica, 66 (6,9%) tenían carcinoma anal de células escamosas. 32 pacientes (48,5%) eran varones y la mediana de edad fue de 57 años (rango 31-79). 10 pacientes (15%) tenían carcinoma anal primario de células escamosas, 49 (74%) tenían un tumor recurrente y 7 (11%) tenían una segunda recurrencia. 22 (33%) y 16 pacientes (24%) tuvieron una complicación mayor y regreso no planificado al quirófano, respectivamente. De los 62 pacientes que se sometieron a una exenteración pélvica con intención curativa, 50 (81%) tuvieron una resección R0, las tasas de supervivencia global y libre de recidiva local a los 5 años fueron del 41% y el 37%, respectivamente. La resección R0 se asoció con una mayor supervivencia general a los 5 años (50% frente a 8%, p < 0,001). Las puntuaciones del componente de salud mental y varios dominios de calidad de vida individuales presentaron trayectorias mejoradas después de la operación (todos los valores de p < 0,05).LIMITACIONES:La generalización de los hallazgos fuera de los centros especializados en exenteración pélvica puede ser limitada.CONCLUSIONES:Los resultados de morbilidad, supervivencia a largo plazo y calidad de vida después de la EP para el carcinoma anal de células escamosas son comparables a los resultados publicados de la exenteración pélvica para otros tipos de tumores. (Traducción-Dr. Ingrid Melo ).
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Affiliation(s)
- Kilian G M Brown
- Department of Colorectal Surgery, Royal Prince Alfred Hospital, Sydney, Australia
- Surgical Outcomes Research Centre (SOuRCe), Royal Prince Alfred Hospital, Sydney, Australia
- Institute of Academic Surgery (IAS), Royal Prince Alfred Hospital, Sydney, Australia
- Faculty of Medicine and Health, Central Clinical School, The University of Sydney, New South Wales, Australia
| | - Michael J Solomon
- Department of Colorectal Surgery, Royal Prince Alfred Hospital, Sydney, Australia
- Surgical Outcomes Research Centre (SOuRCe), Royal Prince Alfred Hospital, Sydney, Australia
- Institute of Academic Surgery (IAS), Royal Prince Alfred Hospital, Sydney, Australia
- Faculty of Medicine and Health, Central Clinical School, The University of Sydney, New South Wales, Australia
| | - Daniel Steffens
- Surgical Outcomes Research Centre (SOuRCe), Royal Prince Alfred Hospital, Sydney, Australia
- Faculty of Medicine and Health, Central Clinical School, The University of Sydney, New South Wales, Australia
| | - Kheng-Seong Ng
- Department of Colorectal Surgery, Royal Prince Alfred Hospital, Sydney, Australia
- Surgical Outcomes Research Centre (SOuRCe), Royal Prince Alfred Hospital, Sydney, Australia
- Institute of Academic Surgery (IAS), Royal Prince Alfred Hospital, Sydney, Australia
- Faculty of Medicine and Health, Central Clinical School, The University of Sydney, New South Wales, Australia
- Department of Colorectal Surgery, Concord Repatriation General Hospital, Sydney, Australia
| | - Christopher M Byrne
- Department of Colorectal Surgery, Royal Prince Alfred Hospital, Sydney, Australia
- Surgical Outcomes Research Centre (SOuRCe), Royal Prince Alfred Hospital, Sydney, Australia
| | - Kirk K S Austin
- Department of Colorectal Surgery, Royal Prince Alfred Hospital, Sydney, Australia
- Surgical Outcomes Research Centre (SOuRCe), Royal Prince Alfred Hospital, Sydney, Australia
- Institute of Academic Surgery (IAS), Royal Prince Alfred Hospital, Sydney, Australia
| | - Peter J Lee
- Department of Colorectal Surgery, Royal Prince Alfred Hospital, Sydney, Australia
- Surgical Outcomes Research Centre (SOuRCe), Royal Prince Alfred Hospital, Sydney, Australia
- Institute of Academic Surgery (IAS), Royal Prince Alfred Hospital, Sydney, Australia
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Borg J, Garm Spindler KL, Havelund BM, Sørensen MM, Funder JA. Risk factors and outcome following salvage surgery for squamous cell carcinoma of the anus. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:107050. [PMID: 37657174 DOI: 10.1016/j.ejso.2023.107050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Revised: 07/08/2023] [Accepted: 08/28/2023] [Indexed: 09/03/2023]
Abstract
BACKGROUND Chemoradiotherapy is the primary treatment for anal cancer. 15-33% of patients will have persistent or recurrent disease after treatment requiring salvage surgery. Relapse after surgery, postoperative complications, and mortality as well as possible risk factors are not fully understood due to the rareness of the disease. The aim of the study was to report outcomes after salvage surgery as well as evaluate risk factors for postoperative complications, cancer relapse and survival. METHODS Data were retrospectively collected from electronical patients charts and pathology reports from all patients undergoing salvage surgery from July 1st, 2011 to July 1st, 2021 at the Department of Surgery, Aarhus University Hospital, Denmark. RESULTS A total of 98 patients were included in the study. The 5-year overall survival was 61.8%. Relapse after surgery occurred in 36.7% of patients and was significantly associated with R1-resection (HR = 4.4) and preoperative nodal metastases (HR = 4.5). Negative prognostic factors for survival were found to be R1-resection (HR = 3.2), preoperative nodal metastases (HR = 2.9), and male gender (HR = 0.5). There was no association found between complications and survival (HR 1.2). None of the possible risk factors were associated with major postoperative complications. CONCLUSIONS An acceptable overall survival after surgery was found. Survival and relapse-free survival was negatively associated with R1 resections and positive preoperative lymph nodes. Complications did not influence long-term survival.
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Affiliation(s)
- Julie Borg
- Department of Surgery, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.
| | - Karen-Lise Garm Spindler
- Department of Oncology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.
| | - Birgitte Mayland Havelund
- Department of Oncology, University Hospital of Southern Denmark, Lillebaelt Hospital, Beriderbakken 4, 7100, Vejle, Denmark.
| | - Mette Møller Sørensen
- Department of Surgery, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.
| | - Jonas Amstrup Funder
- Department of Surgery, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.
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Chen KA, Goffredo P, Hu D, Joisa CU, Guillem JG, Gomez SM, Kapadia MR. Estimating Risk of Locoregional Failure and Overall Survival in Anal Cancer Following Chemoradiation: A Machine Learning Approach. J Gastrointest Surg 2023; 27:1925-1935. [PMID: 37407899 PMCID: PMC10528925 DOI: 10.1007/s11605-023-05755-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 06/03/2023] [Indexed: 07/07/2023]
Abstract
BACKGROUND Optimal treatment of anal squamous cell carcinoma (ASCC) is definitive chemoradiation. Patients with persistent or recurrent disease require abdominoperineal resection (APR). Current models for predicting need for APR and overall survival are limited by low accuracy or small datasets. This study sought to use machine learning (ML) to develop more accurate models for locoregional failure and overall survival for ASCC. METHODS This study used the National Cancer Database from 2004-2018, divided into training, validation, and test sets. We included patients with stage I-III ASCC who underwent chemoradiation. Our primary outcomes were need for APR and 3-year overall survival. Random forest (RF), gradient boosting (XGB), and neural network (NN) ML-based models were developed and compared with logistic regression (LR). Accuracy was assessed using area under the receiver operating characteristic curve (AUROC). RESULTS APR was required in 5.3% (1,015/18,978) of patients. XGB performed best with AUROC of 0.813, compared with 0.691 for LR. Tumor size, lymphovascular invasion, and tumor grade showed the strongest influence on model predictions. Mortality was 23.6% (7,988/33,834). AUROC for XGB and LR were similar at 0.766 and 0.748, respectively. For this model, age, radiation dose, sex, and insurance status were the most influential variables. CONCLUSIONS We developed and internally validated machine learning-based models for predicting outcomes in ASCC and showed higher accuracy versus LR for locoregional failure, but not overall survival. After external validation, these models may assist clinicians with identifying patients with ASCC at high risk of treatment failure.
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Affiliation(s)
- Kevin A Chen
- Divison of Gastrointestinal Surgery, Department of Surgery, University of North Carolina at Chapel Hill, 100 Manning Drive, 4038 Burnett Womack Building, CB #7050, Chapel Hill, NC, 27599, USA
| | - Paolo Goffredo
- Division of Colon & Rectal Surgery, Department of Surgery, University of Minnesota, 420 Delaware St SE, MN, 55455, Minneapolis, USA
| | - David Hu
- Department of Biostatistics, UNC Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 3101 McGavran-Greenberg Hall, CB #7420, Chapel Hill, NC, 27599-7420, USA
| | - Chinmaya U Joisa
- Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, 10202C Mary Ellen Jones Building, Chapel Hill, NC, 27599, USA
| | - Jose G Guillem
- Divison of Gastrointestinal Surgery, Department of Surgery, University of North Carolina at Chapel Hill, 100 Manning Drive, 4038 Burnett Womack Building, CB #7050, Chapel Hill, NC, 27599, USA
| | - Shawn M Gomez
- Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, 10202C Mary Ellen Jones Building, Chapel Hill, NC, 27599, USA
| | - Muneera R Kapadia
- Divison of Gastrointestinal Surgery, Department of Surgery, University of North Carolina at Chapel Hill, 100 Manning Drive, 4038 Burnett Womack Building, CB #7050, Chapel Hill, NC, 27599, USA.
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Jaraudias C, Saint LMA, Schiappa R, Baron D, Marie L, Benezery K, Scouarnec C, François É, Evesque L. Failure of Initial Curative Treatment for Non-Metastatic Anal Squamous Cell Carcinoma: From Prognostic Factors Analysis to Stratified Treatment. Clin Colorectal Cancer 2022; 21:362-370. [PMID: 35934635 DOI: 10.1016/j.clcc.2022.07.001] [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: 10/24/2021] [Revised: 03/14/2022] [Accepted: 07/03/2022] [Indexed: 01/26/2023]
Abstract
In squamous cell anal canal neoplasms, persistent disease or recurrence after initial chemoradiotherapy are not the rule, yet their occurrence deserves to be analyzed to better identify prognostics factors. The aim of our study was to describe the patterns of failures of the initial treatment, their subsequent evolution and to identify prognostic factors in these relapsed patients. All patients with non-metastatic anal squamous cell carcinoma initially treated with curative intent at the Centre Antoine Lacassagne between 1999 and 2019, and who presented persistent disease or recurrence were analyzed. The median follow-up was 44 months. Univariate and multivariate analyses were performed to identify prognostic factors. From our database of 528 patients, 77 patients were eligible: 25 with persistent disease and 52 with recurrence after complete response. The median overall survival was 39 months (95% CI: 25.5-52.3 months) from the date of treatment failure. In univariate analysis, prognostic factors were gender, initial lymph node status, type of failure, response to treatment's failure. In multivariate analysis, only female gender remained statistically significant (HR 0.43- P=0.016). 32% of patients with persistent disease had metastatic status. 17.3% and 5.8% of recurrences respectively occurred after three and five years of follow-up. Systematic imaging could be performed after initial treatment because of distant lesions in one third of patients with persistent disease. The follow-up should not be interrupted before five years, given the significant frequency of late recurrences. In multivariate analysis, only female gender was statistically significant. Stratified treatment based on prognostic factors could be envisaged, the details of which remain to be defined.
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Affiliation(s)
- Claire Jaraudias
- Department of Medical Oncology, Centre Antoine Lacassagne, 33 Avenue Valombrose 06100 Nice, France.
| | | | - Renaud Schiappa
- Department of Epidemiology, Biostatistics and Health Data, Centre Antoine Lacassagne, 33 Avenue Valombrose 06100 Nice, France
| | - David Baron
- Department of Radiotherapy, Centre Antoine Lacassagne, 33 Avenue Valombrose 06100 Nice, France
| | - Léa Marie
- Department of Medical Oncology, Centre Antoine Lacassagne, 33 Avenue Valombrose 06100 Nice, France
| | - Karen Benezery
- Department of Radiotherapy, Centre Antoine Lacassagne, 33 Avenue Valombrose 06100 Nice, France
| | - Cyrielle Scouarnec
- Department of Radiotherapy, Centre Antoine Lacassagne, 33 Avenue Valombrose 06100 Nice, France
| | - Éric François
- Department of Medical Oncology, Centre Antoine Lacassagne, 33 Avenue Valombrose 06100 Nice, France
| | - Ludovic Evesque
- Department of Medical Oncology, Centre Antoine Lacassagne, 33 Avenue Valombrose 06100 Nice, France
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8
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Mesorectal failure after chemoradiotherapy for squamous cell carcinoma of the anus: is sphincter-saving surgery reasonable? Tech Coloproctol 2022; 27:379-388. [PMID: 36127625 DOI: 10.1007/s10151-022-02698-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 09/01/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND Abdominoperineal resection (APR) is today the standard treatment for improving survival in case of mesorectal failure without anal canal recurrence after chemoradiotherapy (CRT) for squamous cell carcinoma of the anus (SCC). The aim of this study was to assess if a sphincter-saving surgery is a safe alternative to classical salvage APR in these patients. METHODS A retrospective study was conducted on all patients who had total mesorectal excision (TME) with sphincter-saving surgery either with coloanal or low colorectal anastomosis, for mesorectal failure after CRT for SCC between 2012 and 2020 at our institution. The main endpoint of our study was oncological results at the end of follow-up. Postoperative morbidity and mortality were secondary endpoints. RESULTS There were 10 patients, (8 women, median age 55 years [range 45-61 years]). On TME specimens, R0 resections were noted in five (50%), R1 resection in four (40%) and R2 resection in one (10%). After a median follow-up of 42 months (4-74 months), five patients were alive, and four (40%) were alive at 5-year follow-up. During follow-up, locoregional failure after TME was noted in two patients (20%), distant relapse in three patients (30%) and both locoregional plus distant failure in two patients (20%). Only two patients (20%) had anal recurrence, one in the anal canal, the other in the peri-anastomotic area. Long- term local control was achieved in 2 of the 5 patients (40%) who underwent R0 resection versus only 1/4 patients (25%) with R1 resection. CONCLUSIONS Our preliminary study suggested that sphincter-saving surgery could be proposed in selected patients with SCC presenting mesorectal failure after CRT, providing a feasible R0 resection.
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9
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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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10
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Damasceno AM, Kesley R, Paolino BS, Dos Santos do Amaral MR, Pitombo MB. Perioperative score for octogenarian patients eligible for rectal cancer surgery. J Surg Oncol 2021; 124:1409-1416. [PMID: 34363616 DOI: 10.1002/jso.26634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 07/08/2021] [Accepted: 07/29/2021] [Indexed: 11/14/2022]
Abstract
BACKGROUND AND OBJECTIVES Colorectal cancer incidence increases with age; therefore, rectal cancer treatment in elderly patients is increasingly common. Surgery is a common rectal cancer treatment, and the risks involve complicated surgical decisions. There are currently few surgical outcome data for rectal cancer in elderly patients. The aim of this study is to identify new perioperative risk factors that could be associated with higher 30- and 180-day mortality in elderly patients in good clinical condition considering traditional perioperative risk scores and to develop a risk score. METHODS A single-centre, retrospective cohort study was performed by reviewing the medical records of patients from the National Cancer Institute of Brazil aged 80 years or older who electively underwent rectal cancer surgery; several independent variables correlated with death from all causes at 30 and 180 days were studied. RESULTS Multivariate analysis found new variables (CEA, albumin and reoperation) that had independent correlations with increased 30- and 180-day mortality. A clinical risk score was developed with survival profiles ranging from 29.3% to 97.2% within 30 days and 2.45% to 91.8% within 180 days. CONCLUSIONS This score can aid in deciding whether a patient should undergo rectal cancer surgery.
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Affiliation(s)
- Arthur Mota Damasceno
- Post-Graduate Program in Medical Sciences (PGCM), Medical Sciences College (FCM), Rio de Janeiro State University (UERJ), Rio de Janeiro, Rio de Janeiro, Brazil
| | - Rubens Kesley
- Department of Abdominal Surgery, National Cancer Institute of Brazil (INCA), Rio de Janeiro, Rio de Janeiro, Brazil
| | - Bruno Souza Paolino
- Post-Graduate Program in Medical Sciences (PGCM), Medical Sciences College (FCM), Rio de Janeiro State University (UERJ), Rio de Janeiro, Rio de Janeiro, Brazil
| | - Marcelo Rubens Dos Santos do Amaral
- Post-Graduate Program in Medical Sciences (PGCM), Medical Sciences College (FCM), Rio de Janeiro State University (UERJ), Rio de Janeiro, Rio de Janeiro, Brazil
| | - Marcos Bettini Pitombo
- Post-Graduate Program in Medical Sciences (PGCM), Medical Sciences College (FCM), Rio de Janeiro State University (UERJ), Rio de Janeiro, Rio de Janeiro, Brazil
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11
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12
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Maccabe TA, Parwaiz I, Longman RJ, Thomas MG, Messenger DE. Outcomes following local excision of early anal squamous cell carcinomas of the anal canal and perianal margin. Colorectal Dis 2021; 23:689-697. [PMID: 33140913 DOI: 10.1111/codi.15424] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 10/14/2020] [Accepted: 10/28/2020] [Indexed: 12/20/2022]
Abstract
AIM There is a paucity of data on outcomes from local excision (LE) of early anal squamous cell carcinomas (ASCCs). This study aimed to assess survival outcomes according to tumour location, perianal (PAT) or anal canal (ACT), and to determine factors associated with R1 excision and outcomes according to T-category. METHODS This was a retrospective cohort study of consecutive patients with early ASCC treated by LE from 2007 to 2019. Data were collected on baseline demographics, tumour location, staging, excision histology, adjuvant treatment, site and timing of recurrence. The main outcome measures were R1 resection, locoregional recurrence (LRR), disease-free survival and overall survival. RESULTS Of 367 patients treated for ASCC, 39 (10.6%) patients with complete follow-up data underwent LE: 15 ACTs and 24 PATs. R1 resections were obtained in 27 patients (69.2%) and occurred more frequently in ACTs than PATs (93.3% vs. 54.2%, P = 0.006). Eighteen of 27 patients (66.7%) received adjuvant therapy (chemoradiotherapy [n = 11], radiotherapy alone [n = 7]) for R1 excision or re-excision, following which LRR developed in one of 10 (10.0%) patients in the ACT cohort and one of eight (12.5%) patients in the PAT cohort. There was no difference in 5-year LRR-free survival (82.0% vs. 70.1%, P = 0.252), disease-free survival (58.2% vs. 78.4%, P = 0.200) or overall survival (86.2% vs. 95.7%, P = 0.607) between the ACT and PAT cohorts. CONCLUSIONS LE is a feasible treatment option for early ASCCs of the perianal margin but not the anal canal. Acceptable long-term outcomes can still be achieved with adjuvant therapy in the presence of a positive margin. Larger prospective studies to assess LE as a treatment strategy, such as the ACT3 trial, are warranted.
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Affiliation(s)
- Tom A Maccabe
- Department of Colorectal Surgery, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
| | - Iram Parwaiz
- Department of Colorectal Surgery, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
| | - Robert J Longman
- Department of Colorectal Surgery, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
| | - Michael G Thomas
- Department of Colorectal Surgery, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
| | - David E Messenger
- Department of Colorectal Surgery, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
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13
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Park IJ, Chang G. Survival and Operative Outcomes After Salvage Surgery for Recurrent or Persistent Anal Cancer. Ann Coloproctol 2020; 36:361-373. [PMID: 33486907 PMCID: PMC7837391 DOI: 10.3393/ac.2020.12.29] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 12/29/2020] [Indexed: 12/24/2022] Open
Abstract
Anal squamous cell carcinoma (SCC) is a relatively rare cancer comprising less than 2.5% of all gastrointestinal malignancies. The standard treatment for anal SCC is primary chemoradiation therapy which can result in complete regression. After successful treatment, the 5-year survival is approximately 80%. However, up to 30% of patients experience recurrent persistent or recurrent disease. The role of surgery in the treatment of anal cancer, therefore, is limited to the management of recurrent or persistent disease with abdominoperineal resection and/or en bloc adjacent organ excision. Salvage surgery after irradiated anal cancer can be technically demanding in terms of acquisition of oncologically safe surgical margins and minimization of postoperative morbidity. In addition, 5-year survival outcomes after salvage resection have been reported to vary from 23% to 69%. Positive resection margins are generally regarded as the important risk factor associated with poor survival outcome. Perineal wound complications are the most common major postoperative morbidity. Because of the challenges of primary wound closure after salvage abdominoperineal resection, myocutaneous flap reconstruction has been performed to reduce the severity of perianal would complications. We, therefore, descriptively reviewed contemporary published evidence describing the treatment and outcomes after salvage surgery for persistent or recurrent anal SCC.
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Affiliation(s)
- In Ja Park
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine Seoul, Korea
| | - George Chang
- Department of Colon and Rectal Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA
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14
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Goldner M, Platoff R, Betances A, De Leo N, Gaughan J, Hageboutros A, Atabek U, Spitz FR, Hong YK. Role of metastasectomy for liver metastasis in stage IV anal cancer. Am J Surg 2020; 221:832-838. [PMID: 32883493 DOI: 10.1016/j.amjsurg.2020.08.016] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 07/20/2020] [Accepted: 08/16/2020] [Indexed: 12/22/2022]
Abstract
INTRODUCTION There is a paucity of data on the role of metastasectomy for metastatic anal cancer on survival outcomes. We aim to define the role of metastasectomy in stage IV anal cancer. METHODS National Cancer Database (NCDB) from 2004 to 2014 was accessed to include patients with metastatic anal cancer, excluding adenocarcinoma, neuroendocrine, and 'other' histologies. We compared patients undergoing metastasectomy (n = 165) to those who did not have metastasectomy (n = 2093) by age, sex, cancer grade, and site of metastasis, including metastasis to bone, liver, and lung, using chi-square analysis. The primary outcome was overall survival. RESULTS Patients had equal distribution of metastatic sites between those who underwent metastasectomy versus no metastasectomy: bone (7.64% vs 4.85%, p = 0.22), brain (0.24% vs 0%, p = 1.0), liver (23.22% vs 29.70%, p = 0.07), and lung (11.85% vs 9.09%, p = 0.38). Survival following metastasectomy was increased at one year (71% vs. 61%, p = 0.016), two years (50% vs. 38%, p = 0.014), and five years (30% vs. 19%, p = 0.025). Median overall survival was increased (23 months vs. 16 months; p = 0.015) for patients with metastasectomy. Survival increases were demonstrated only in the group with liver metastasis undergoing metastasectomy. When stratifying for liver metastases only, median overall survival time was further increased (34 months vs. 16 months; p < 0.0001) following metastasectomy. CONCLUSION These results demonstrate a survival benefit for hepatic metastasectomy in stage IV anal cancer. Our findings demonstrate a potential survival benefit in highly select patients with metastatic anal cancer to the liver. These findings support further investigation in a randomized clinical trial to delineate these findings.
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Affiliation(s)
- Matthew Goldner
- Division of Surgical Oncology, Department of Surgery, Cooper University Hospital, 3 Cooper Plaza, Suite 411, Camden, NJ, 08103, USA
| | - Rebecca Platoff
- Division of Surgical Oncology, Department of Surgery, Cooper University Hospital, 3 Cooper Plaza, Suite 411, Camden, NJ, 08103, USA
| | - Avril Betances
- Division of Surgical Oncology, Department of Surgery, Cooper University Hospital, 3 Cooper Plaza, Suite 411, Camden, NJ, 08103, USA
| | - Nicholas De Leo
- Division of Surgical Oncology, Department of Surgery, Cooper University Hospital, 3 Cooper Plaza, Suite 411, Camden, NJ, 08103, USA
| | - John Gaughan
- Division of Surgical Oncology, Department of Surgery, Cooper University Hospital, 3 Cooper Plaza, Suite 411, Camden, NJ, 08103, USA
| | - Alexandre Hageboutros
- Division of Surgical Oncology, Department of Surgery, Cooper University Hospital, 3 Cooper Plaza, Suite 411, Camden, NJ, 08103, USA
| | - Umur Atabek
- Division of Surgical Oncology, Department of Surgery, Cooper University Hospital, 3 Cooper Plaza, Suite 411, Camden, NJ, 08103, USA
| | - Francis R Spitz
- Division of Surgical Oncology, Department of Surgery, Cooper University Hospital, 3 Cooper Plaza, Suite 411, Camden, NJ, 08103, USA
| | - Young K Hong
- Division of Surgical Oncology, Department of Surgery, Cooper University Hospital, 3 Cooper Plaza, Suite 411, Camden, NJ, 08103, USA.
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15
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Bingmer K, Ofshteyn A, Dietz DW, Stein SL, Steinhagen E. Outcomes in immunosuppressed anal cancer patients. Am J Surg 2019; 219:88-92. [PMID: 31477240 DOI: 10.1016/j.amjsurg.2019.08.011] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Revised: 08/07/2019] [Accepted: 08/13/2019] [Indexed: 10/26/2022]
Abstract
BACKGROUND Immunosuppressed patients have an increased risk of developing anal cancer, but little data exists regarding outcomes of this population. METHODS A retrospective review of anal cancer patients at a single academic institution from 2006 to 2017 was performed. RESULTS 19 (14%) of 136 anal cancer patients were immunosuppressed. Immunosuppressed patients were more likely to be hypoalbuminemic (21% vs. 6%, p = 0.025), less likely to complete chemotherapy (58% vs. 80%, p = 0.031) or exhibit a complete response to chemoradiation (57% vs. 82%, p = 0.037), and more likely to experience recurrence (53% vs. 25%, p = 0.013). Hypoalbuminemia was significantly associated with worse overall (HR 6.4, CI 2.2-19.2, p < 0.001) and progression-free (HR 4.4, CI 1.8-10.4, p < 0.001) survival. CONCLUSIONS Immunosuppressed patients have poor tolerance of chemotherapy and response to chemoradiation, and an increased rate of recurrence. This finding is possibly due to the relationship between immunosuppression and hypoalbuminemia, which was associated with worse overall and progression-free survival.
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Affiliation(s)
- Katherine Bingmer
- University Hospitals Research in Surgical Outcomes & Effectiveness Center (UH-RISES), Department of Surgery, University Hospitals, Cleveland Medical Center, Cleveland, OH, USA
| | - Asya Ofshteyn
- University Hospitals Research in Surgical Outcomes & Effectiveness Center (UH-RISES), Department of Surgery, University Hospitals, Cleveland Medical Center, Cleveland, OH, USA
| | - David W Dietz
- University Hospitals Research in Surgical Outcomes & Effectiveness Center (UH-RISES), Department of Surgery, University Hospitals, Cleveland Medical Center, Cleveland, OH, USA
| | - Sharon L Stein
- University Hospitals Research in Surgical Outcomes & Effectiveness Center (UH-RISES), Department of Surgery, University Hospitals, Cleveland Medical Center, Cleveland, OH, USA
| | - Emily Steinhagen
- University Hospitals Research in Surgical Outcomes & Effectiveness Center (UH-RISES), Department of Surgery, University Hospitals, Cleveland Medical Center, Cleveland, OH, USA.
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16
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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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17
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Fields AC, Melnitchouk N, Senturk J, Irani J, Bleday R, Goldberg J. Early versus late salvage abdominoperineal resection for anal squamous cell carcinoma: Is there a difference in survival? J Surg Oncol 2019; 120:287-293. [PMID: 31055841 DOI: 10.1002/jso.25489] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Revised: 04/01/2019] [Accepted: 04/18/2019] [Indexed: 11/10/2022]
Abstract
BACKGROUND/OBJECTIVES The first-line treatment for anal squamous cell carcinoma is Nigro protocol chemoradiotherapy. Some patients will fail curative intent chemoradiotherapy and have persistent disease while others may have an initial response followed by disease recurrence. The goal of this study is to investigate survival in anal squamous cell carcinoma patients who fail first-line treatment. METHODS The National Cancer Database (2004-2013) was used to identify patients with anal squamous cell carcinoma. The primary outcome was overall survival. RESULTS There were 256 patients in the early salvage group who underwent abdominoperineal resection (APR) within 6 months of completing chemoradiotherapy and 181 patients in the late salvage group who had APR 6 months or more after completion of chemoradiotherapy. Both groups of patients had similar tumor size (45 vs 50 mm; P = 0.07) and rate of positive margins (21.5% vs 15.6%;P = 0.13). There was no significant difference in overall survival between early and late salvage APR (hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.50-1.32; P = 0.40). CONCLUSIONS The overall survival of anal squamous cell carcinoma patients undergoing early vs late salvage APR after failure of chemoradiotherapy is similar. As a result, patients with persistent disease should be offered surgery just as readily as those with recurrent disease.
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Affiliation(s)
- Adam C Fields
- Department of Surgery, Division of Colorectal Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Nelya Melnitchouk
- Department of Surgery, Division of Colorectal Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - James Senturk
- Department of Surgery, Division of Colorectal Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Jennifer Irani
- Department of Surgery, Division of Colorectal Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Ronald Bleday
- Department of Surgery, Division of Colorectal Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Joel Goldberg
- Department of Surgery, Division of Colorectal Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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18
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Abstract
Anal cancer is a rare condition, although its incidence has been increasing over the past several decades, particularly in women. The majority of anal cancers are squamous cell cancers and are linked with human papilloma virus (HPV) infection. Recent work in HPV basic science has delineated the mechanism by which the virus leads to the development of anal cancer. With widespread availability of an HPV vaccine since 2006, vaccination has become an important strategy for anal cancer prevention. However, in the US, there remain no guidelines for anal cancer screening. Treatment of anal cancer is dictated largely by accurate staging, which is generally accomplished with a combination of physical exam, magnetic resonance imaging, computed tomography, and positron emission tomography. Chemoradiation remains the mainstay of treatment for most patients, with surgery reserved for salvage therapy. Recent trials have identified the optimal use of available chemotherapeutics. Exciting developments in immune therapies targeting HPV oncoproteins as well as therapeutic vaccines may soon dramatically change the way patients with anal cancer are managed.
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Affiliation(s)
- Matthew M. Symer
- New York-Presbyterian Hospital/Weill Cornell Medicine, Department of Surgery, 525 East 68th Street, New York, NY 10065, USA
| | - Heather L. Yeo
- New York-Presbyterian Hospital/Weill Cornell Medicine, Department of Surgery, 525 East 68th Street, New York, NY 10065, USA
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19
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Cacheux W, Tsantoulis P, Briaux A, Vacher S, Mariani P, Richard-Molard M, Buecher B, Richon S, Jeannot E, Lazartigues J, Rouleau E, Mariani O, El Alam E, Cros J, Roman-Roman S, Mitry E, Girard E, Dangles-Marie V, Lièvre A, Bièche I. Array comparative genomic hybridization identifies high level of PI3K/Akt/mTOR pathway alterations in anal cancer recurrences. Cancer Med 2018; 7:3213-3225. [PMID: 29804324 PMCID: PMC6051172 DOI: 10.1002/cam4.1533] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Revised: 04/04/2018] [Accepted: 04/06/2018] [Indexed: 01/31/2023] Open
Abstract
Genomic alterations of anal squamous cell carcinoma (ASCC) remain poorly understood due to the rarity of this tumor. Array comparative genomic hybridization and targeted gene sequencing were performed in 49 cases of ASCC. The most frequently altered regions (with a frequency greater than 25%) were 10 deleted regions (2q35, 2q36.3, 3p21.2, 4p16.3, 4p31.21, 7q36.1, 8p23.3, 10q23.2, 11q22.3, and 13q14.11) and 8 gained regions (1p36.33, 1q21.1, 3q26.32, 5p15.33, 8q24.3, 9q34.3, 16p13.3, and 19p13.3). The most frequent minimal regions of deletion (55%) encompassed the 11q22.3 region containing ATM, while the most frequent minimal regions of gain (57%) encompassed the 3q26.32 region containing PIK3CA. Recurrent homozygous deletions were observed for 5 loci (ie, TGFR2 in 4 cases), and recurrent focal amplifications were observed for 8 loci (ie, DDR2 and CCND1 in 3 cases, respectively). Several of the focal amplified genes are targets for specific therapies. Integrated analysis showed that the PI3K/Akt/mTOR signaling pathway was the pathway most extensively affected, particularly in recurrences compared to treatment‐naive tumors (64% vs 30%; P = .017). In patients with ASCC recurrences, poor overall survival (OS) was significantly correlated with a large number of altered regions (P = .024). These findings provide insight into the somatic genomic alterations in ASCC and highlight the key role of the druggable PI3K/Akt/mTOR signaling pathway.
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Affiliation(s)
- Wulfran Cacheux
- Département d'oncologie médicale, Institut Curie, Ensemble hospitalier, Hôpital René Huguenin, Saint-Cloud, France.,Unité de pharmacogénomique, Département de génétique, Institut Curie, Ensemble hospitalier, Paris Cedex 05, France
| | - Petros Tsantoulis
- Centre d'oncologie, Hôpitaux universitaires de Genève, Genève, Switzerland
| | - Adrien Briaux
- Unité de pharmacogénomique, Département de génétique, Institut Curie, Ensemble hospitalier, Paris Cedex 05, France
| | - Sophie Vacher
- Unité de pharmacogénomique, Département de génétique, Institut Curie, Ensemble hospitalier, Paris Cedex 05, France
| | - Pascale Mariani
- Département de chirurgie oncologique, Institut Curie, Ensemble hospitalier, Paris Cedex 05, France
| | - Marion Richard-Molard
- Département de radio-oncologie, Institut Curie, Ensemble hospitalier, Hôpital René Huguenin, Saint-Cloud, France
| | - Bruno Buecher
- Département d'oncologie médicale, Institut Curie, Ensemble hospitalier, Paris Cedex 05, France
| | - Sophie Richon
- Centre de recherche, Institut Curie, UMR144, Paris Cedex 05, France
| | - Emmanuelle Jeannot
- Département d'anatomopathologie, Institut Curie, Ensemble hospitalier, Paris Cedex 05, France
| | - Julien Lazartigues
- Unité de pharmacogénomique, Département de génétique, Institut Curie, Ensemble hospitalier, Paris Cedex 05, France
| | - Etienne Rouleau
- Unité de pharmacogénomique, Département de génétique, Institut Curie, Ensemble hospitalier, Paris Cedex 05, France
| | - Odette Mariani
- Département d'anatomopathologie, Institut Curie, Ensemble hospitalier, Paris Cedex 05, France
| | - Elsy El Alam
- Département d'anatomopathologie, Institut Curie, Ensemble hospitalier, Hôpital René Huguenin, Saint-Cloud, France
| | - Jérôme Cros
- Unité de pharmacogénomique, Département de génétique, Institut Curie, Ensemble hospitalier, Paris Cedex 05, France
| | - Sergio Roman-Roman
- Recherche translationnelle, Centre de recherche, Institut Curie, Paris Cedex 05, France
| | - Emmanuel Mitry
- Département d'oncologie médicale, Institut Curie, Ensemble hospitalier, Hôpital René Huguenin, Saint-Cloud, France
| | - Elodie Girard
- Département de bio-informatiques, Centre de recherche, Institut Curie, Paris Cedex 05, France
| | - Virginie Dangles-Marie
- Recherche translationnelle, Centre de recherche, Institut Curie, Paris Cedex 05, France.,IFR71, Faculté des sciences biologique et pharmacologiques, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - Astrid Lièvre
- Département d'oncologie médicale, Institut Curie, Ensemble hospitalier, Hôpital René Huguenin, Saint-Cloud, France.,Département de gastroentérologie, Hôpital universitaire de Rennes, Université de Rennes 1, Rennes, France
| | - Ivan Bièche
- Unité de pharmacogénomique, Département de génétique, Institut Curie, Ensemble hospitalier, Paris Cedex 05, France
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20
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Hagemans JAW, Blinde SE, Nuyttens JJ, Morshuis WG, Mureau MAM, Rothbarth J, Verhoef C, Burger JWA. Salvage Abdominoperineal Resection for Squamous Cell Anal Cancer: A 30-Year Single-Institution Experience. Ann Surg Oncol 2018; 25:1970-1979. [PMID: 29691737 PMCID: PMC5976705 DOI: 10.1245/s10434-018-6483-9] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Indexed: 12/14/2022]
Abstract
Background Failure of chemoradiotherapy (CRT) for anal squamous cell carcinoma (SCC) results in persistent or recurrent anal SCC. Treatment with salvage abdominoperineal resection (APR) can potentially achieve cure. The aims of this study are to analyze oncological and surgical outcomes of our 30-year experience with salvage APR for anal SCC after failed CRT and identify prognostic factors for overall survival (OS). Methods All consecutive patients who underwent salvage APR between 1990 and 2016 for histologically confirmed persistent or recurrent anal SCC after failed CRT were retrospectively analyzed. Results Forty-seven patients underwent salvage APR for either persistent (n = 24) or recurrent SCC (n = 23). Median OS was 47 months [95% confidence interval (CI) 10.0–84.0 months] and 5-year survival was 41.6%, which did not differ significantly between persistent or recurrent disease (p = 0.551). Increased pathological tumor size (p < 0.001) and lymph node involvement (p = 0.014) were associated with impaired hazard for OS on multivariable analysis, and irradical resection only (p = 0.001) on univariable analysis. Twenty-one patients developed local recurrence after salvage APR, of whom 8 underwent repeat salvage surgery and 13 received palliative treatment. Median OS was 9 months (95% CI 7.2–10.8 months) after repeat salvage surgery and 4 months (95% CI 2.8–5.1 months) following palliative treatment (p = 0.055). Conclusions Salvage APR for anal SCC after failed CRT resulted in adequate survival, with 5-year survival of 41.6%. Negative prognostic factors for survival were increased tumor size, lymph node involvement, and irradical resection. Patients with recurrent anal SCC after salvage APR had poor prognosis, irrespective of performance of repeat salvage surgery, which never resulted in cure.
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Affiliation(s)
- J A W Hagemans
- Department of Surgical Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
| | - S E Blinde
- Department of Radiation Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - J J Nuyttens
- Department of Radiation Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - W G Morshuis
- Department of Anesthesiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - M A M Mureau
- Department of Plastic and Reconstructive Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - J Rothbarth
- Department of Surgical Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - C Verhoef
- Department of Surgical Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - J W A Burger
- Department of Surgical Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
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21
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Gauthé M, Richard-Molard M, Rigault E, Buecher B, Mariani P, Bellet D, Cacheux W, Lièvre A. Prognostic value of serum CYFRA 21-1 1 in patients with anal canal squamous cell carcinoma treated with radio(chemo)therapy. BMC Cancer 2018; 18:417. [PMID: 29653564 PMCID: PMC5899349 DOI: 10.1186/s12885-018-4335-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2017] [Accepted: 04/04/2018] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND We aimed to assess the prognostic value of CYFRA 21-1 in a series of patients with anal canal squamous cell carcinoma treated by radiation-based therapy. METHODS All patients with anal cancer referred between September 2005 and July 2013 were considered. Patients with diagnosis of anal squamous cell carcinoma and in whom pre- and post-treatment serum CYFRA 21-1 levels were available were included. Serum CYFRA 21-1 levels at initial workup and after therapy were collected. Survival rates were estimated using the Kaplan-Meier method. Cox regression analysis was used to evaluate prognostic variables for prediction of outcomes. RESULTS Eighty-two patients were included. Median follow-up was 60 months (range: 8-128). Pre-treatment serum CYFRA 21-1 levels were significantly correlated with tumour stage (p < 0.001). Normal post-treatment serum CYFRA 21-1 level was significantly correlated with tumour complete response (p = 0.004). Elevated post-treatment serum CYFRA 21-1 level was significantly associated with poorer progression-free survival (p = 0.02) and overall survival (p = 0.003). T stage and post-treatment serum CYFRA 21-1 were independent prognostic factors for overall survival (p = 0.04 and 0.03, respectively). CONCLUSIONS Serum CYFRA 21-1 appears to be a useful marker for the monitoring of anal squamous cell carcinoma patients. Elevated post-treatment value appears to be correlated with treatment failure.
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Affiliation(s)
- Mathieu Gauthé
- Médecine nucléaire, Institut Curie, Hôpital Paris, 26 rue d'Ulm, 75005, Paris, France. .,Médecine nucléaire, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, 4 rue de la Chine, 75020, Paris, France. .,Université Pierre et Marie Curie, 4 Place Jussieu, Paris, France.
| | - Marion Richard-Molard
- Département de radiothérapie, Institut Curie, Hôpital René Huguenin, 35 rue Dailly, 92210, Saint-Cloud, France
| | - Eugénie Rigault
- Service des maladies de l'appareil digestif, Centre Hospitalier Universitaire de Rennes, 2 rue Henri Le Guilloux, Rennes, 35033, France.,Faculté de Médecine, Université de Rennes 1, 2 avenue du Pr. Léon Bernard, 35043, Rennes, France.,INSERM U1242, COSS (chemistry, oncogenesis, stress and signaling), , Rue Bataille Flandres-Dunkerque, 35043, Rennes, France
| | - Bruno Buecher
- Département d'oncologie médicale, Institut Curie, Hôpital Paris, 26 rue d'Ulm, 75005, Paris, France
| | - Pascale Mariani
- Département de chirurgie oncologique, Institut Curie, Hôpital Paris, 26 rue d'Ulm, 75005, Paris, France
| | - Dominique Bellet
- Laboratoire d'oncobiologie, Département de biopathologie, Institut Curie, Hôpital René Huguenin, 35 rue Dailly, 92210, Saint-Cloud, France
| | - Wulfran Cacheux
- Département d'oncologie médicale, Institut Curie, Hôpital René Huguenin, 35 rue Dailly, 92210, Saint-Cloud, France.,Unité de pharmacogénomique, département de génétique, Institut Curie, Hôpital Paris, 26 rue d'Ulm, 75005, Paris, France
| | - Astrid Lièvre
- Service des maladies de l'appareil digestif, Centre Hospitalier Universitaire de Rennes, 2 rue Henri Le Guilloux, Rennes, 35033, France.,Faculté de Médecine, Université de Rennes 1, 2 avenue du Pr. Léon Bernard, 35043, Rennes, France.,Département d'oncologie médicale, Institut Curie, Hôpital René Huguenin, 35 rue Dailly, 92210, Saint-Cloud, France
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22
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What is the impact of neoadjuvant chemoradiation on outcomes in gastro-intestinal cancer? J Visc Surg 2017; 154:185-195. [DOI: 10.1016/j.jviscsurg.2017.05.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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23
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Severino NP, Chadi SA, Rosen L, Coiro S, Choman E, Berho M, Wexner SD. Survival following salvage abdominoperineal resection for persistent and recurrent squamous cell carcinoma of the anus: do these disease categories affect survival? Colorectal Dis 2016; 18:959-966. [PMID: 26850085 DOI: 10.1111/codi.13288] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2015] [Accepted: 12/01/2015] [Indexed: 02/08/2023]
Abstract
AIM This study aimed to investigate the results of salvage abdominoperineal excision (APR) in patients with persistent or recurrent squamous cell carcinoma of the anus (SCCA). METHOD Patients with anal neoplasia were identified from a prospective database. Patients with invasive SCCA with demonstrated failure of chemoradiation therapy (CRT) who underwent salvage APR for one of three disease categories (persistent, < 6 months post-CRT; early recurrent, 6-24 months post-CRT; late recurrent, > 24 months post-CRT) were included. The primary outcome was overall survival after salvage APR. Tumour size, metastatic lymph nodes (LN), circumferential resection margin positivity (CRM) and neurolymphovascular invasion (NLVI) were correlated with the outcome. RESULTS Thirty-six patients with a median 3-year overall survival of 46% (median follow-up 24 months) underwent salvage APR due to persistent or recurrent SCCA (14 men, mean age 59 years). Eleven (31%) patients were diagnosed with persistent disease, 17 (47%) with early and 8 (22%) with late recurrence. Two-year overall survival of Stage 0/I/II and III/IV disease was 81.5% and 33.74%, respectively (P = 0.022). Overall disease stage was associated with disease categorization (P = 0.009): patients with persistent disease or early recurrence had a significantly higher disease stage than patients with late recurrence (OR = 20.9 and 17.2). Despite apparently improved survival in patients with late disease recurrence on live table analysis, no significant difference was identified in overall survival when stratified by disease category on log-rank test analysis. CONCLUSION Persistent and recurrent disease does not show any significant difference in survival, but patients with late recurrence may have a better prognosis.
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Affiliation(s)
- N P Severino
- Department of Colorectal Surgery, Cleveland Clinic Florida, Weston, Florida, USA
| | - S A Chadi
- Department of Colorectal Surgery, Cleveland Clinic Florida, Weston, Florida, USA
| | - L Rosen
- Department of Colorectal Surgery, Cleveland Clinic Florida, Weston, Florida, USA
| | - S Coiro
- Department of Colorectal Surgery, Cleveland Clinic Florida, Weston, Florida, USA
| | - E Choman
- Department of Colorectal Surgery, Cleveland Clinic Florida, Weston, Florida, USA
| | - M Berho
- Department of Pathology, Cleveland Clinic Florida, Weston, Florida, USA
| | - S D Wexner
- Department of Colorectal Surgery, Cleveland Clinic Florida, Weston, Florida, USA.
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24
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Leeds IL, Alturki H, Canner JK, Schneider EB, Efron JE, Wick EC, Gearhart SL, Safar B, Fang SH. Outcomes of abdominoperineal resection for management of anal cancer in HIV-positive patients: a national case review. World J Surg Oncol 2016; 14:208. [PMID: 27495294 PMCID: PMC4974747 DOI: 10.1186/s12957-016-0970-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2016] [Accepted: 08/02/2016] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The incidence of anal cancer in human immunodeficiency virus (HIV)-positive individuals is increasing, and how co-infection affects outcomes is not fully understood. This study sought to describe the current outcome disparities between anal cancer patients with and without HIV undergoing abdominoperineal resection (APR). METHODS A retrospective review of all US patients diagnosed with anal squamous cell carcinoma, undergoing an APR, was performed. Cases were identified using a weighted derivative of the Healthcare Utilization Project's National Inpatient Sample (2000-2011). Patients greater than 60 years old were excluded after finding a skewed population distribution between those with and without HIV infection. Multivariable logistic regression and generalized linear modeling analysis examined factors associated with postoperative outcomes and cost. Perioperative complications, in-hospital mortality, length of hospital stay, and hospital costs were compared for those undergoing APR with and without HIV infection. RESULTS A total of 1725 patients diagnosed with anal squamous cell cancer undergoing APR were identified, of whom 308 (17.9 %) were HIV-positive. HIV-positive patients were younger than HIV-negative patients undergoing APR for anal cancer (median age 47 years old versus 51 years old, p < 0.001) and were more likely to be male (95.1 versus 30.6 %, p < 0.001). Postoperative hemorrhage was more frequent in the HIV-positive group (5.1 versus 1.5 %, p = 0.05). Mortality was low in both groups (0 % in HIV-positive versus 1.49 % in HIV-negative, p = 0.355), and length of stay (LOS) (10+ days; 75th percentile of patient data) was similar (36.9 % with HIV versus 29.8 % without HIV, p = 0.262). Greater hospitalization costs were associated with patients who experienced a complication. However, there was no difference in hospitalization costs seen between HIV-positive and HIV-negative patients (p = 0.66). CONCLUSIONS HIV status is not associated with worse postoperative recovery after APR for anal cancer as measured by length of stay or hospitalization cost. Further study may support APRs to be used more aggressively in HIV-positive patients with anal cancer.
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Affiliation(s)
- Ira L Leeds
- Department of Surgery, The Johns Hopkins Hospital, 600 North Wolfe Street, Blalock 618, Baltimore, MD, 21287, USA.
| | - Hasan Alturki
- Johns Hopkins Surgery Center for Outcomes Research, Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA
| | - Joseph K Canner
- Johns Hopkins Surgery Center for Outcomes Research, Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA
| | - Eric B Schneider
- Johns Hopkins Surgery Center for Outcomes Research, Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA
| | - Jonathan E Efron
- Department of Surgery, The Johns Hopkins Hospital, 600 North Wolfe Street, Blalock 618, Baltimore, MD, 21287, USA
| | - Elizabeth C Wick
- Department of Surgery, The Johns Hopkins Hospital, 600 North Wolfe Street, Blalock 618, Baltimore, MD, 21287, USA
| | - Susan L Gearhart
- Department of Surgery, The Johns Hopkins Hospital, 600 North Wolfe Street, Blalock 618, Baltimore, MD, 21287, USA
| | - Bashar Safar
- Department of Surgery, The Johns Hopkins Hospital, 600 North Wolfe Street, Blalock 618, Baltimore, MD, 21287, USA
| | - Sandy H Fang
- Department of Surgery, The Johns Hopkins Hospital, 600 North Wolfe Street, Blalock 618, Baltimore, MD, 21287, USA
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25
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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: 13] [Impact Index Per Article: 1.4] [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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26
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Mutational analysis of anal cancers demonstrates frequent PIK3CA mutations associated with poor outcome after salvage abdominoperineal resection. Br J Cancer 2016; 114:1387-94. [PMID: 27219019 PMCID: PMC4984471 DOI: 10.1038/bjc.2016.144] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2016] [Revised: 04/19/2016] [Accepted: 04/27/2016] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND A better understanding of the molecular profile of anal squamous cell carcinomas (ASCCs) is necessary to consider new therapeutic approaches, and the identification of prognostic and predictive factors for response to treatment. METHODS We retrospectively analysed tumours from ASCC patients for mutational analysis of KRAS, NRAS, HRAS, BRAF, PIK3CA, MET, TP53 and FBXW7 genes by HRM and Sanger sequencing analysis. RESULTS Specimens from 148 patients were analysed: 96 treatment-naive tumours and 52 recurrences after initial radiotherapy (RT) or chemoradiotherapy (CRT). Mutations of KRAS, PIK3CA, FBXW7 and TP53 genes were present in 3 (2.0%), 30 (20.3%), 9 (6.1%) and 7 tumours (4.7%), respectively. The distribution of the mutations was similar between treatment-naive tumours and recurrences, except for TP53 mutations being more frequent in recurrences (P=0.0005). In patients treated with abdominoperineal resection (APR) after relapse (n=38, median follow-up of 18.2 years), overall survival (OS) was significantly correlated with HPV16 status (P=0.048), gender (P=0.045) and PIK3CA mutation (P=0.037). The PIK3CA status retained its prognostic significance in Cox multivariate regression analysis (P=0.025). CONCLUSIONS Our study identified PIK3CA mutation as an independent prognostic factor in patients who underwent APR for ASCC recurrence, suggesting a potential benefit from adjuvant treatment and the evaluation of targeted therapies with PI3K/Akt/mTor inhibitors in PIK3CA-mutated patients.
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27
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Salvage abdominoperineal excisions in recurrent anal cancer--impact of different reconstruction techniques on outcome, morbidity, and complication rates. Int J Colorectal Dis 2016; 31:653-9. [PMID: 26686872 DOI: 10.1007/s00384-015-2474-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/14/2015] [Indexed: 02/04/2023]
Abstract
BACKGROUND Squamous cell cancer of the anus (SCCA) is a rare disease of the gastrointestinal tract. Even though chemoradiation therapy is the treatment of choice, a substantial number of patients develop recurrent cancers or present with persisting SCCA. Therefore, abdominoperineal excisions as a salvage therapy are the only chance of cure. PATIENTS AND METHODS Hospital files of all patients with recurrent squamous cell carcinoma of the anus who underwent abdominoperineal excision performed at the Department of General and Visceral Surgery of the University Hospital Frankfurt between January 2003 and December 2013 were retrospectively reviewed. RESULTS Fourteen (nine males, five females) patients underwent abdominoperineal resections for recurrent SCCA. In six patients, the pelvic floor was closed by direct suture, four patients underwent reconstruction using a vertical rectus abdominis myocutaneous (VRAM) flap, and four patients received a gluteal myocutaneous flap. Patients receiving flap-mediated closure revealed a median hospital stay of 26 days (range 13-60 days) compared to 11 days (range 9-30 days) in patients with direct closure (p = 0.01). Two patients (14%) suffered from wound infections (Dindo-Clavien II), whereas three patients (21%) underwent up to seven reoperations for breakdown of their wounds and/or laparotomies (Dindo-Clavien IIIb). The calculated 5-year survival rate was 86%. Patients with rpT0/T1 stage had a significantly longer survival compared to patients presenting with rpT2/T3/T4 tumors. CONCLUSION Abdominoperineal excisions in patients with recurrent SCCA can provide long-term local control and survival. The complication rate is not associated with the closure technique employed, but patients undergoing flap-mediated closure revealed a significantly longer hospital stay.
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28
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Goldman KE, White EC, Rao AR, Kaptein JS, Lien WW. Posttreatment FDG-PET-CT response is predictive of tumor progression and survival in anal carcinoma. Pract Radiat Oncol 2016; 6:e149-e154. [PMID: 26948134 DOI: 10.1016/j.prro.2016.01.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2015] [Revised: 01/04/2016] [Accepted: 01/08/2016] [Indexed: 01/22/2023]
Abstract
PURPOSE We hypothesize that posttreatment F-18 fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) metabolic response predicts clinical outcomes in patients with anal cancer treated with chemoradiation. METHODS AND MATERIALS This was a single-institution retrospective review of 148 patients treated definitively for anal squamous cell carcinoma between 2005 and 2012. All patients were followed with posttreatment PET-CT scans and clinical examinations. Progression-free survival (PFS), cause-specific survival, and overall survival (OS) estimates were calculated using the Kaplan-Meier method. RESULTS The median follow-up was 34 months (range, 5-89 months). Pretreatment PET was successful in detecting the primary tumor in 140 cases (95%). Computed tomography (CT) alone was able to detect primary tumors in 78 of 122 patients who had pretreatment CT scans (64%). Inguinal or pelvic lymph nodes were FDG avid in 68 patients, with only 41 of these patients having enlarged lymph nodes by CT criteria (60.3%). Initial posttreatment PET-CT was obtained on average 12.7 ± 4.3 weeks after the last day of radiation (range, 5-25 weeks). Overall complete metabolic response (CR) on initial PET-CT was found in 82 patients (58%). Partial metabolic response was noted in 52 (36.9%) and progression in 7 patients (5%). Only 12/82 patients (14.6%) with a FDG-PET CR eventually recurred. The negative predictive value of a PET-CT scan performed between 13 and 25 weeks posttreatment was 92.9%. The 2-year PFS for patients with CR versus non-CR was 89.8% and 69.2%, respectively (P = .004). The 2-year OS for CR versus non-CR patients was 94.8% and 79.3% (P = .036). CONCLUSIONS Complete metabolic response on posttreatment FDG PET-CT is highly predictive of increased PFS and OS in patients treated with chemoradiation for anal carcinoma. In addition to close clinical surveillance, we recommend obtaining posttreatment PET-CT scans >12 weeks following definitive treatment for anal cancer.
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Affiliation(s)
- Kelly E Goldman
- Department of Radiation Oncology, Kaiser Permanente Los Angeles Medical Center, Los Angeles, California; Department of Radiation Oncology, Southern California Permanente Medical Group, Los Angeles, California
| | - Evan C White
- Department of Radiation Oncology, Kaiser Permanente Los Angeles Medical Center, Los Angeles, California; Department of Radiation Oncology, Southern California Permanente Medical Group, Los Angeles, California.
| | - Aroor R Rao
- Department of Radiation Oncology, Southern California Permanente Medical Group, Los Angeles, California
| | - John S Kaptein
- Research Laboratory, Southern California Permanente Medical Group, Los Angeles, California
| | - Winston W Lien
- Department of Radiation Oncology, Southern California Permanente Medical Group, Los Angeles, California
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29
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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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30
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Sperandei S. The pits and falls of graphical presentation. Biochem Med (Zagreb) 2014; 24:311-20. [PMID: 25351349 PMCID: PMC4210251 DOI: 10.11613/bm.2014.033] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2014] [Accepted: 08/25/2014] [Indexed: 11/25/2022] Open
Abstract
Graphics are powerful tools to communicate research results and to gain information from data. However, researchers should be careful when deciding which data to plot and the type of graphic to use, as well as other details. The consequence of bad decisions in these features varies from making research results unclear to distortions of these results, through the creation of “chartjunk” with useless information. This paper is not another tutorial about “good graphics” and “bad graphics”. Instead, it presents guidelines for graphic presentation of research results and some uncommon, but useful examples to communicate basic and complex data types, especially multivariate model results, which are commonly presented only by tables. By the end, there are no answers here, just ideas meant to inspire others on how to create their own graphics.
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Affiliation(s)
- Sandro Sperandei
- Institute of Scientific and Technological Communication & Information in Health, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil
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Yu HS, Liu ZM, Yu XY, Song AQ, Liu N, Wang H. Low-dose radiation induces antitumor effects and erythrocyte system hormesis. Asian Pac J Cancer Prev 2014; 14:4121-6. [PMID: 23991963 DOI: 10.7314/apjcp.2013.14.7.4121] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
OBJECTIVE Low dose radiation may stimulate the growth and development of animals, increase life span, enhance fertility, and downgrade the incidence of tumor occurrence.The aim of this study was to investigate the antitumor effect and hormesis in an erythrocyte system induced by low-dose radiation. METHODS Kunming strain male mice were subcutaneously implanted with S180 sarcoma cells in the right inguen as an experimental in situ animal model. Six hours before implantation, the mice were given 75mGy whole body X-ray radiation. Tumor growth was observed 5 days later, and the tumor volume was calculated every other day. Fifteen days later, all mice were killed to measure the tumor weight, and to observe necrotic areas and tumor-infiltration-lymphoreticular cells (TILs). At the same time, erythrocyte immune function and the level of 2,3-diphosphoglyceric acid (2,3- DPG) were determined. Immunohistochemical staining was used to detect the expression of EPO and VEGFR of tumor tissues. RESULTS The mice pre-exposed to low dose radiation had a lower tumor formation rate than those without low dose radiation (P < 0.05). The tumor growth slowed down significantly in mice pre-exposed to low dose radiation; the average tumor weight in mice pre-exposed to low dose radiation was lighter too (P < 0.05). The tumor necrosis areas were larger and TILs were more in the radiation group than those of the group without radiation. The erythrocyte immune function, the level of 2,3-DPG in the low dose radiation group were higher than those of the group without radiation (P < 0.05). After irradiation the expression of EPO of tumor tissues in LDR group decreased with time. LDR-24h, LDR-48h and LDR-72h groups were all statistically significantly different from sham-irradiation group. The expression of VEGFR also decreased, and LDR-24h group was the lowest (P < 0.05). CONCLUSION Low dose radiation could markedly increase the anti-tumor ability of the organism and improve the erythrocyte immune function and the ability of carrying O2. Low-dose total body irradiation, within a certain period of time, can decrease the expression of hypoxia factor EPO and VEGFR, which may improve the situation of tumor hypoxia and radiosensitivity of tumor itself.
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Affiliation(s)
- Hong-Sheng Yu
- Department of Oncology, the Affiliated Hospital of Medical College, Qingdao University, Qingdao, China.
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