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Title: Consensus Recommendations for Radiation Therapy Contouring and Treatment of Vulvar Carcinoma

Abstract

Purpose: The purpose of this study was to develop a radiation therapy (RT) contouring atlas and recommendations for women with postoperative and locally advanced vulvar carcinoma. Methods and Materials: An international committee of 35 expert gynecologic radiation oncologists completed a survey of the treatment of vulvar carcinoma. An initial set of recommendations for contouring was discussed and generated by consensus. Two cases, 1 locally advanced and 1 postoperative, were contoured by 14 physicians. Contours were compared and analyzed using an expectation-maximization algorithm for simultaneous truth and performance level estimation (STAPLE), and a 95% confidence interval contour was developed. The level of agreement among contours was assessed using a kappa statistic. STAPLE contours underwent full committee editing to generate the final atlas consensus contours. Results: Analysis of the 14 contours showed substantial agreement, with kappa statistics of 0.69 and 0.64 for cases 1 and 2, respectively. There was high specificity for both cases (≥99%) and only moderate sensitivity of 71.3% and 64.9% for cases 1 and 2, respectively. Expert review and discussion generated consensus recommendations for contouring target volumes and treatment for postoperative and locally advanced vulvar cancer. Conclusions: These consensus recommendations for contouring and treatment of vulvar cancer identified areasmore » of complexity and controversy. Given the lack of clinical research evidence in vulvar cancer radiation therapy, the committee advocates a conservative and consistent approach using standardized recommendations.« less

Authors:
 [1];  [2];  [3];  [4];  [5];  [6];  [7];  [8];  [9];  [10]; ;  [6];  [11];  [12];  [13];  [14];
  1. Department of Radiation Oncology, Huntsman Cancer Hospital, Salt Lake City, Utah (United States)
  2. Department of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre and Epworth Radiation Oncology, Melbourne, Victoria (Australia)
  3. Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts (United States)
  4. Department of Radiation Oncology, Centre hospitalier de l'universite de Montreal, Montreal, Quebec (Canada)
  5. Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States)
  6. Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas (United States)
  7. Department of Radiation Oncology, Proedtert and Medical College Clinical Cancer Center, Milwaukee, Wisconsin (United States)
  8. Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario (Canada)
  9. Department of Radiation Oncology, British Columbia Cancer Agency, Victoria, British Columbia (Canada)
  10. Department of Radiation Oncology, Stritch School of Medicine, Loyola University, Maywood, Illinois (United States)
  11. Department of Radiation Oncology, University of Washington, Seattle, Washington (United States)
  12. Liverpool Cancer Therapy Centre, Radiation Oncology Unit, Sydney, New South Wales (Australia)
  13. Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States)
  14. Radiation Oncology Department, Miller School of Medicine, University of Miami, Miami, Florida (United States)
Publication Date:
OSTI Identifier:
22648735
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 95; Journal Issue: 4; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CARCINOMAS; RADIOTHERAPY; RECOMMENDATIONS; SURGERY; UTERUS

Citation Formats

Gaffney, David K., E-mail: david.gaffney@hci.utah.edu, King, Bronwyn, Viswanathan, Akila N., Barkati, Maroie, Beriwal, Sushil, Eifel, Patricia, Erickson, Beth, Fyles, Anthony, Goulart, Jennifer, Harkenrider, Matthew, Jhingran, Anuja, Klopp, Ann, Koh, Wui-Jin, Lim, Karen, Petersen, Ivy, Portelance, Lorraine, and and others. Consensus Recommendations for Radiation Therapy Contouring and Treatment of Vulvar Carcinoma. United States: N. p., 2016. Web. doi:10.1016/J.IJROBP.2016.02.043.
Gaffney, David K., E-mail: david.gaffney@hci.utah.edu, King, Bronwyn, Viswanathan, Akila N., Barkati, Maroie, Beriwal, Sushil, Eifel, Patricia, Erickson, Beth, Fyles, Anthony, Goulart, Jennifer, Harkenrider, Matthew, Jhingran, Anuja, Klopp, Ann, Koh, Wui-Jin, Lim, Karen, Petersen, Ivy, Portelance, Lorraine, & and others. Consensus Recommendations for Radiation Therapy Contouring and Treatment of Vulvar Carcinoma. United States. doi:10.1016/J.IJROBP.2016.02.043.
Gaffney, David K., E-mail: david.gaffney@hci.utah.edu, King, Bronwyn, Viswanathan, Akila N., Barkati, Maroie, Beriwal, Sushil, Eifel, Patricia, Erickson, Beth, Fyles, Anthony, Goulart, Jennifer, Harkenrider, Matthew, Jhingran, Anuja, Klopp, Ann, Koh, Wui-Jin, Lim, Karen, Petersen, Ivy, Portelance, Lorraine, and and others. 2016. "Consensus Recommendations for Radiation Therapy Contouring and Treatment of Vulvar Carcinoma". United States. doi:10.1016/J.IJROBP.2016.02.043.
@article{osti_22648735,
title = {Consensus Recommendations for Radiation Therapy Contouring and Treatment of Vulvar Carcinoma},
author = {Gaffney, David K., E-mail: david.gaffney@hci.utah.edu and King, Bronwyn and Viswanathan, Akila N. and Barkati, Maroie and Beriwal, Sushil and Eifel, Patricia and Erickson, Beth and Fyles, Anthony and Goulart, Jennifer and Harkenrider, Matthew and Jhingran, Anuja and Klopp, Ann and Koh, Wui-Jin and Lim, Karen and Petersen, Ivy and Portelance, Lorraine and and others},
abstractNote = {Purpose: The purpose of this study was to develop a radiation therapy (RT) contouring atlas and recommendations for women with postoperative and locally advanced vulvar carcinoma. Methods and Materials: An international committee of 35 expert gynecologic radiation oncologists completed a survey of the treatment of vulvar carcinoma. An initial set of recommendations for contouring was discussed and generated by consensus. Two cases, 1 locally advanced and 1 postoperative, were contoured by 14 physicians. Contours were compared and analyzed using an expectation-maximization algorithm for simultaneous truth and performance level estimation (STAPLE), and a 95% confidence interval contour was developed. The level of agreement among contours was assessed using a kappa statistic. STAPLE contours underwent full committee editing to generate the final atlas consensus contours. Results: Analysis of the 14 contours showed substantial agreement, with kappa statistics of 0.69 and 0.64 for cases 1 and 2, respectively. There was high specificity for both cases (≥99%) and only moderate sensitivity of 71.3% and 64.9% for cases 1 and 2, respectively. Expert review and discussion generated consensus recommendations for contouring target volumes and treatment for postoperative and locally advanced vulvar cancer. Conclusions: These consensus recommendations for contouring and treatment of vulvar cancer identified areas of complexity and controversy. Given the lack of clinical research evidence in vulvar cancer radiation therapy, the committee advocates a conservative and consistent approach using standardized recommendations.},
doi = {10.1016/J.IJROBP.2016.02.043},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 4,
volume = 95,
place = {United States},
year = 2016,
month = 7
}
  • Purpose: To define a male and female pelvic normal tissue contouring atlas for Radiation Therapy Oncology Group (RTOG) trials. Methods and Materials: One male pelvis computed tomography (CT) data set and one female pelvis CT data set were shared via the Image-Guided Therapy QA Center. A total of 16 radiation oncologists participated. The following organs at risk were contoured in both CT sets: anus, anorectum, rectum (gastrointestinal and genitourinary definitions), bowel NOS (not otherwise specified), small bowel, large bowel, and proximal femurs. The following were contoured in the male set only: bladder, prostate, seminal vesicles, and penile bulb. The followingmore » were contoured in the female set only: uterus, cervix, and ovaries. A computer program used the binomial distribution to generate 95% group consensus contours. These contours and definitions were then reviewed by the group and modified. Results: The panel achieved consensus definitions for pelvic normal tissue contouring in RTOG trials with these standardized names: Rectum, AnoRectum, SmallBowel, Colon, BowelBag, Bladder, UteroCervix, Adnexa{sub R}, Adnexa{sub L}, Prostate, SeminalVesc, PenileBulb, Femur{sub R}, and Femur{sub L}. Two additional normal structures whose purpose is to serve as targets in anal and rectal cancer were defined: AnoRectumSig and Mesorectum. Detailed target volume contouring guidelines and images are discussed. Conclusions: Consensus guidelines for pelvic normal tissue contouring were reached and are available as a CT image atlas on the RTOG Web site. This will allow uniformity in defining normal tissues for clinical trials delivering pelvic radiation and will facilitate future normal tissue complication research.« less
  • Purpose: To develop a Radiation Therapy Oncology Group (RTOG) atlas of the elective clinical target volume (CTV) definitions to be used for planning pelvic intensity-modulated radiotherapy (IMRT) for anal and rectal cancers. Methods and Materials: The Gastrointestinal Committee of the RTOG established a task group (the nine physician co-authors) to develop this atlas. They responded to a questionnaire concerning three elective CTVs (CTVA: internal iliac, presacral, and perirectal nodal regions for both anal and rectal case planning; CTVB: external iliac nodal region for anal case planning and for selected rectal cases; CTVC: inguinal nodal region for anal case planning andmore » for select rectal cases), and to outline these areas on individual computed tomographic images. The imaging files were shared via the Advanced Technology Consortium. A program developed by one of the co-authors (I.E.N.) used binomial maximum-likelihood estimates to generate a 95% group consensus contour. The computer-estimated consensus contours were then reviewed by the group and modified to provide a final contouring consensus atlas. Results: The panel achieved consensus CTV definitions to be used as guidelines for the adjuvant therapy of rectal cancer and definitive therapy for anal cancer. The most important difference from similar atlases for gynecologic or genitourinary cancer is mesorectal coverage. Detailed target volume contouring guidelines and images are discussed. Conclusion: This report serves as a template for the definition of the elective CTVs to be used in IMRT planning for anal and rectal cancers, as part of prospective RTOG trials.« less
  • Purpose: To examine clinical outcomes and relapse patterns in locally advanced vulvar carcinoma treated using preoperative chemotherapy and intensity modulated radiation therapy (IMRT). Methods and Materials: Forty-two patients with stage I-IV{sub A} (stage I, n=3; stage II, n=13; stage III, n=23; stage IV{sub A}, n=3) vulvar cancer were treated with chemotherapy and IMRT via a modified Gynecological Oncology Group schema using 5-fluorouracil and cisplatin with twice-daily IMRT during the first and last weeks of treatment or weekly cisplatin with daily radiation therapy. Median dose of radiation was 46.4 Gy. Results: Thirty-three patients (78.6%) had surgery for resection of vulva; 13more » of these patients also had inguinal lymph node dissection. Complete pathologic response was seen in 48.5% (n=16) of these patients. Of these, 15 had no recurrence at a median time of 26.5 months. Of the 17 patients with partial pathological response, 8 (47.1%) developed recurrence in the vulvar surgical site within a median of 8 (range, 5-34) months. No patient had grade ≥3 chronic gastrointestinal/genitourinary toxicity. Of those having surgery, 8 (24.2%) developed wound infections requiring debridement. Conclusions: Preoperative chemotherapy/IMRT was well tolerated, with good pathologic response and clinical outcome. The most common pattern of recurrence was local in patients with partial response, and strategies to increase pathologic response rate with increasing dose or adding different chemotherapy need to be explored to help further improve outcomes.« less
  • Purpose: Positive surgical margins after radical vulvectomy for vulvar cancer portend a high risk for local relapse, which may be challenging to salvage. We assessed the impact of adjuvant radiation therapy (aRT) on overall survival (OS) and the dose-response relationship using the National Cancer Data Base. Methods and Materials: Patients with vulvar squamous cell carcinoma who underwent initial extirpative surgery with positive margins from 1998 to 2012 were included. Factors associated with aRT and specific dose levels were analyzed using logistic regression. Log-rank and multivariable Cox proportional hazards modeling were used for OS analysis. Results: We identified 3075 patients withmore » a median age of 66 years (range, 22-90 years); the median follow-up time was 36.4 months (interquartile range [IQR] 15.4-71.0 months). Stage IA/B disease represented 41.2% of the cohort. Sixty-three percent underwent lymph node assessment, with a 45% positivity rate. In total, 1035 patients (35.3%) received aRT, with a median dose of 54.0 Gy (IQR 48.6-60.0 Gy). The 3-year OS improved from 58.5% to 67.4% with aRT (P<.001). On multivariable analysis, age, Charlson-Deyo score ≥1, stage ≥II, tumors ≥4 cm, no aRT, and adverse nodal characteristics led to inferior survival. Dose of aRT was positively associated with OS as a continuous variable on univariate analysis (P<.001). The unadjusted 3-year OS for dose subsets 30.0 to 45.0 Gy, 45.1 to 53.9 Gy, 54.0 to 59.9 Gy, and ≥60 Gy was 54.3%, 55.7%, 70.1%, and 65.3%, respectively (P<.001). Multivariable analysis using a 4-month conditional landmark revealed that the greatest mortality reduction occurred in cumulative doses ≥54 Gy: 45.1 to 53.9 Gy (hazard ratio [HR] 0.94, P=.373), 54.0 to 59.9 Gy (HR 0.75, P=.024), ≥60 Gy (HR 0.71, P=.015). No survival benefit was seen with ≥60 Gy compared with 54.0 to 59.9 Gy (HR 0.95, P=.779). Conclusions: Patients with vulvar squamous cell carcinoma and positive surgical margins derive an OS benefit from aRT with a seemingly optimal dose in the range of 54.0 to 59.9 Gy.« less
  • Purpose: The purpose of this study was to establish reproducible guidelines for delineating the clinical target volume (CTV) of the pelvic lymph nodes (LN) by combining the freehand Royal Marsden Hospital (RMH) and Radiation Therapy Oncology Group (RTOG) vascular expansion techniques. Methods and Materials: Seven patients with prostate cancer underwent standard planning computed tomography scanning. Four different CTVs (RMH, RTOG, modified RTOG, and Prostate and pelvIs Versus prOsTate Alone treatment for Locally advanced prostate cancer [PIVOTAL] trial) were created for each patient, and 6 different bowel expansion margins (BEM) were created to assess bowel avoidance by the CTV. The resulting CTVsmore » were compared visually and by using Jaccard conformity indices. The volume of overlap between bowel and planning target volume (PTV) was measured to aid selection of an appropriate BEM to enable maximal LN yet minimal normal tissue coverage. Results: In total, 84 nodal contours were evaluated. LN coverage was similar in all groups, with all of the vascular-expansion techniques (RTOG, modified RTOG, and PIVOTAL), resulting in larger CTVs than that of the RMH technique (mean volumes: 287.3 cm{sup 3}, 326.7 cm{sup 3}, 310.3 cm{sup 3}, and 256.7 cm{sup 3}, respectively). Mean volumes of bowel within the modified RTOG PTV were 19.5 cm{sup 3} (with 0 mm BEM), 17.4 cm{sup 3} (1-mm BEM), 10.8 cm{sup 3} (2-mm BEM), 6.9 cm{sup 3} (3-mm BEM), 5.0 cm{sup 3} (4-mm BEM), and 1.4 cm{sup 3} (5-mm BEM) in comparison with an overlap of 9.2 cm{sup 3} seen using the RMH technique. Evaluation of conformity between LN-CTVs from each technique revealed similar volumes and coverage. Conclusions: Vascular expansion techniques result in larger LN-CTVs than the freehand RMH technique. Because the RMH technique is supported by phase 1 and 2 trial safety data, we proposed modifications to the RTOG technique, including the addition of a 3-mm BEM, which resulted in LN-CTV coverage similar to that of the RMH technique, with reduction in bowel and planning target volume overlap. On the basis of these findings, recommended guidelines including a detailed pelvic LN contouring atlas have been produced and implemented in the PIVOTAL trial.« less