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      Management and Care of Women With Invasive Cervical Cancer: American Society of Clinical Oncology Resource-Stratified Clinical Practice Guideline

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          Abstract

          Purpose

          To provide evidence-based, resource-stratified global recommendations to clinicians and policymakers on the management and palliative care of women diagnosed with invasive cervical cancer.

          Methods

          ASCO convened a multidisciplinary, multinational panel of cancer control, medical and radiation oncology, health economic, obstetric and gynecologic, and palliative care experts to produce recommendations reflecting resource-tiered settings. A systematic review of literature from 1966 to 2015 failed to yield sufficiently strong quality evidence to support basic- and limited-resource setting recommendations; a formal consensus-based process was used to develop recommendations. A modified ADAPTE process was also used to adapt recommendations from existing guidelines.

          Results

          Five existing sets of guidelines were identified and reviewed, and adapted recommendations form the evidence base. Eight systematic reviews, along with cost-effectiveness analyses, provided indirect evidence to inform the consensus process, which resulted in agreement of 75% or greater.

          Recommendations

          Clinicians and planners should strive to provide access to the most effective evidence-based antitumor and palliative care interventions. If a woman cannot access these within her own or neighboring country or region, she may need to be treated with lower-tier modalities, depending on capacity and resources for surgery, chemotherapy, radiation therapy, and supportive and palliative care. For women with early-stage cervical cancer in basic settings, cone biopsy or extrafascial hysterectomy may be performed. Fertility-sparing procedures or modified radical or radical hysterectomy may be additional options in nonbasic settings. Combinations of surgery, chemotherapy, and radiation therapy (including brachytherapy) should be used for women with stage IB to IVA disease, depending on available resources. Pain control is a vital component of palliative care. Additional information is available at www.asco.org/rs-cervical-cancer-treatment-guideline and www.asco.org/guidelineswiki. It is the view of ASCO that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines.

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          Most cited references47

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          Improved survival with bevacizumab in advanced cervical cancer.

          Vascular endothelial growth factor (VEGF) promotes angiogenesis, a mediator of disease progression in cervical cancer. Bevacizumab, a humanized anti-VEGF monoclonal antibody, has single-agent activity in previously treated, recurrent disease. Most patients in whom recurrent cervical cancer develops have previously received cisplatin with radiation therapy, which reduces the effectiveness of cisplatin at the time of recurrence. We evaluated the effectiveness of bevacizumab and nonplatinum combination chemotherapy in patients with recurrent, persistent, or metastatic cervical cancer. Using a 2-by-2 factorial design, we randomly assigned 452 patients to chemotherapy with or without bevacizumab at a dose of 15 mg per kilogram of body weight. Chemotherapy consisted of cisplatin at a dose of 50 mg per square meter of body-surface area, plus paclitaxel at a dose of 135 or 175 mg per square meter or topotecan at a dose of 0.75 mg per square meter on days 1 to 3, plus paclitaxel at a dose of 175 mg per square meter on day 1. Cycles were repeated every 21 days until disease progression, the development of unacceptable toxic effects, or a complete response was documented. The primary end point was overall survival; a reduction of 30% in the hazard ratio for death was considered clinically important. Groups were well balanced with respect to age, histologic findings, performance status, previous use or nonuse of a radiosensitizing platinum agent, and disease status. Topotecan-paclitaxel was not superior to cisplatin-paclitaxel (hazard ratio for death, 1.20). With the data for the two chemotherapy regimens combined, the addition of bevacizumab to chemotherapy was associated with increased overall survival (17.0 months vs. 13.3 months; hazard ratio for death, 0.71; 98% confidence interval, 0.54 to 0.95; P=0.004 in a one-sided test) and higher response rates (48% vs. 36%, P=0.008). Bevacizumab, as compared with chemotherapy alone, was associated with an increased incidence of hypertension of grade 2 or higher (25% vs. 2%), thromboembolic events of grade 3 or higher (8% vs. 1%), and gastrointestinal fistulas of grade 3 or higher (3% vs. 0%). The addition of bevacizumab to combination chemotherapy in patients with recurrent, persistent, or metastatic cervical cancer was associated with an improvement of 3.7 months in median overall survival. (Funded by the National Cancer Institute; GOG 240 ClinicalTrials.gov number, NCT00803062.).
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            Prospective surgical-pathological study of disease-free interval in patients with stage IB squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study.

            There were 732 evaluable patients with primary, previously untreated, histologically confirmed stage I squamous carcinoma of the cervix with greater than or equal to 3-mm invasion. Of these, 645 had no gross disease beyond the cervix/uterus, had negative paraaortic lymph nodes, and had undergone a radical hysterectomy with pelvic lymphadenectomy. The 3-year disease-free interval (DFIs) for the 545 patients with negative pelvic nodes was 85.6%, and for the 100 with positive pelvic nodes, 74.4%. A large number of pelvic nodes involved with tumor was not correlated with a poorer prognosis; the DFIs were 72.1, 86.4, and 64.6% for one, two, and three or more positive pelvic nodes, respectively. DFI correlated strongly with depth of tumor invasion, both in absolute terms (mm) and infractional thirds. The DFI was 94.6% for less than or equal to 5 mm, 86.0% for 6-10 mm, 75.2% for 11-15 mm, 71.5% for 16-20 mm, and 59.5% greater than or equal to 21 mm. In fractional terms, the DFI was 94.1% for superficial third, 84.5% for middle third, and 73.6% for deep third invasion. With respect to clinical tumor size, the DFIs were 94.8, 88.1, and 67.6% for occult, less than or equal to 3 cm, and greater than 3 cm, respectively. The DFI was 77.0% for those with positive capillary-lymphatic spaces (CLS) and 88.9% for those with negative CLS. Tumor grade and parametrial status correlated with DFI. DFI was not significantly different for age, disease status of the surgical margins, tumor description (e.g., exophytic), quadrant involved with tumor, uterine extension, and keratinizing status of tumor cells. Clinical tumor size, CLS, and depth of tumor invasion were independent prognostic factors.
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              American Brachytherapy Society consensus guidelines for locally advanced carcinoma of the cervix. Part II: high-dose-rate brachytherapy.

              This report presents an update to the American Brachytherapy Society (ABS) high-dose-rate (HDR) brachytherapy guidelines for locally advanced cervical cancer. Members of the ABS with expertise in cervical cancer formulated updated guidelines for HDR brachytherapy using tandem and ring, ovoids, cylinder, or interstitial applicators for locally advanced cervical cancer. These guidelines were written based on medical evidence in the literature and input of clinical experts in gynecologic brachytherapy. The ABS affirms the essential curative role of tandem-based brachytherapy in the management of locally advanced cervical cancer. Proper applicator selection, insertion, and imaging are fundamental aspects of the procedure. Three-dimensional imaging with magnetic resonance or computed tomography or radiographic imaging may be used for treatment planning. Dosimetry must be performed after each insertion before treatment delivery. Applicator placement, dose specification, and dose fractionation must be documented, quality assurance measures must be performed, and followup information must be obtained. A variety of dose/fractionation schedules and methods for integrating brachytherapy with external-beam radiation exist. The recommended tumor dose in 2-Gray (Gy) per fraction radiobiologic equivalence (normalized therapy dose) is 80-90Gy, depending on tumor size at the time of brachytherapy. Dose limits for normal tissues are discussed. These guidelines update those of 2000 and provide a comprehensive description of HDR cervical cancer brachytherapy in 2011. Copyright © 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                J Glob Oncol
                J Glob Oncol
                jgo
                jgo
                JGO
                Journal of global oncology
                American Society of Clinical Oncology
                2378-9506
                October 2016
                25 May 2016
                : 2
                : 5
                : 311-340
                Affiliations
                [1] Linus T. Chuang, Icahn School of Medicine at Mt Sinai, New York, NY; Sarah Temin, American Society of Clinical Oncology, Alexandria, VA; Rolando Camacho, retired, Mallorca, Spain; Alfonso Dueñas-Gonzalez, Instituto Nacional de Cancerologia, Mexico City, Mexico; Sarah Feldman, Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Boston, MA; Murat Gultekin, Turkish Ministry of Health, Ankara, Turkey; Vandana Gupta, patient representative, V Care Foundation, Mumbai, India; Susan Horton, University of Waterloo, Waterloo; Gillian Thomas, Sunnybrook Odette Cancer Centre and University of Toronto, Toronto, Ontario, Canada; Graciela Jacob, Instituto Nacional de Cancerologia, Buenos Aires, Argentina; Elizabeth A. Kidd and Jonathan S. Berek, Stanford Comprehensive Cancer Institute, Stanford, CA; Kennedy Lishimpi, Cancer Diseases Hospital, Lusaka, Zambia; Carolyn Nakisige, Mulago Hospital, Kampala, Uganda; Joo-Hyun Nam, Asan Medical Center, Seoul, South Korea; Hextan Yuen Sheung Ngan, University of Hong Kong, Hong Kong, Special Administrative Region, People’s Republic of China; and William Small, Cardinal Bernardin Cancer Center, Stritch School of Medicine, Loyola University, Chicago, IL.
                Author notes
                Corresponding author: American Society of Clinical Oncology, 2318 Mill Rd, Suite 800, Alexandria, VA 22314; e-mail: guidelines@ 123456asco.org .
                Article
                003954
                10.1200/JGO.2016.003954
                5493265
                28717717
                9168e5d5-964b-489a-8c6f-89198b718a84
                © 2016 by American Society of Clinical Oncology

                Licensed under the Creative Commons Attribution 4.0 License: http://creativecommons.org/licenses/by-nc-nd/4.0/.

                History
                Page count
                Figures: 0, Tables: 11, Equations: 0, References: 63, Pages: 30
                Categories
                ASCO Guidelines
                Diagnosis & Staging
                Surgery
                Radiation
                Chemotherapy
                Combined Modality
                Palliative Care
                Radiation Oncology
                Special Articles

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