Management and long-term clinical outcomes of patients with stage IVA cervical cancer with bladder involvement.

OBJECTIVE: To describe the long-term outcomes of patients with stage IVA cervical cancer, a rare and deadly disease for which long-term toxicity data are scarce, to guide clinician counseling and survivorship support. METHODS: In a retrospective review of a prospectively maintained database, we identified 76 patients with stage IVA cervical cancer with biopsy- or MRI-proven bladder mucosal involvement who received definitive radiotherapy (external beam radiotherapy [EBRT] alone or EBRT plus brachytherapy) with or without chemotherapy at our institution between 2000 and 2020. We used Kaplan-Meier modeling to estimate recurrence-free survival (RFS) and overall survival (OS) and used proportional hazard modeling to identify clinical variables associated with recurrence or survival. We performed actuarial competing risk modeling for severe late toxicity (grades 3 to 5, occurring >6 months of follow-up) and vesicovaginal fistulae (VVF), censoring for pelvic recurrence and death, and made comparisons between potential predictors using Gray's test and binary logistic regression. RESULTS: The median follow-up time was 76 months (interquartile range 58-91). The median OS duration was 35 months (range, 18-not reached), and the 2- and 5-year OS rates were 53.6% and 40.9%, respectively. OS and RFS did not differ significantly between patients who received EBRT alone (N = 18) or EBRT plus brachytherapy (N = 49). Current smoking was a strong predictor of severe late toxicity, whose incidence was 14% at 2 years and 17% at 10 years. The VVF incidence was 24% at 2 years and 32% at 10 years. CONCLUSION: Patients with stage IVA cervical cancer, even those who receive EBRT alone, can have long-term survival. These patients should be followed closely for late radiation-related toxicity.

Quality-adjusted survival in women with gynecologic malignancies receiving IMRT after surgery: A Ppatient Rreported Ooutcome study of NRG oncology's RTOG 1203.

INTRODUCTION: NRG/RTOG 1203 compared 3-D conformal radiotherapy (3D CRT) to intensity-modulated radiotherapy (IMRT) in patients with endometrial or cervical cancer requiring post-operative radiotherapy after hysterectomy. The purpose of this study was to report the first quality-adjusted survival analysis comparing the two treatments. METHODS: NRG/RTOG 1203 randomized patients having undergone hysterectomy to either 3DCRT or IMRT. Stratification factors included RT dose, chemotherapy, and disease site. The EQ-5D, both index and visual analog scale (VAS), were obtained at baseline, 5 weeks after the start of RT, 4-6 weeks post RT and 1 and 3-years post RT. EQ-5D index and VAS scores along with quality-adjusted survival (QAS) were compared between treatment arms using the t-test at a two-sided significance level of 0.05. RESULTS: NRG/RTOG 1203 enrolled 289 patients of which 236 consented to participate in the patient reported outcome (PRO) assessments. QAS was higher in women treated with IMRT, 1374 vs 1333 days (p = 0.5) compared to patients treated with 3DCRT, but this difference was not statistically different. Patients treated with IMRT had less of a decline in VAS score 5 weeks post RT, -5.04, compared to patients treated with 3DCRT, -7.48, although not statistically significant (p = 0.38). CONCLUSION: This is the first report of the use of the EQ-5D comparing two radiotherapy techniques in the treatment of gynecologic malignancies after surgery. While there were no significant differences in QAS and VAS scores between patients who received IMRT vs. 3DCRT, RTOG 1203 was not powered to show statistical differences in these secondary endpoints.

Metagenomes of rectal swabs in larger, advanced stage cervical cancers have enhanced mucus degrading functionalities and distinct taxonomic structure.

BACKGROUND: Gut microbiome community composition differs between cervical cancer (CC) patients and healthy controls, and increased gut diversity is associated with improved outcomes after treatment. We proposed that functions of specific microbial species adjoining the mucus layer may directly impact the biology of CC. METHOD: Metagenomes of rectal swabs in 41 CC patients were examined by whole-genome shotgun sequencing to link taxonomic structures, molecular functions, and metabolic pathway to patient's clinical characteristics. RESULTS: Significant association of molecular functions encoded by the metagenomes was found with initial tumor size and stage. Profiling of the molecular function abundances and their distributions identified 2 microbial communities co-existing in each metagenome but having distinct metabolism and taxonomic structures. Community A (Clostridia and Proteobacteria predominant) was characterized by high activity of pathways involved in stress response, mucus glycan degradation and utilization of degradation byproducts. This community was prevalent in patients with larger, advanced stage tumors. Conversely, community B (Bacteroidia predominant) was characterized by fast growth, active oxidative phosphorylation, and production of vitamins. This community was prevalent in patients with smaller, early-stage tumors. CONCLUSIONS: In this study, enrichment of mucus degrading microbial communities in rectal metagenomes of CC patients was associated with larger, more advanced stage tumors.

Long-term survival following definitive radiation therapy for recurrence or oligometastases in gynecological malignancies: A landmark analysis.

OBJECTIVE: Radiation therapy (RT) may improve outcomes for patients with oligometastatic cancer. We sought to determine if there are long-term survivors treated with definitive RT for recurrent or oligometastatic gynecological cancer (ROMGC), and to evaluate the clinical and disease characteristics of these patients. METHODS: We performed a landmark analysis in 48 patients with ROMGC who survived for ≥5 years following definitive RT of their metastasis. Patient characteristics were extracted from the medical record. DFS was modeled using the Kaplan-Meier method. RESULTS: This cohort included 20 patients (42%) with ovarian cancer, 16 (33%) with endometrial cancer, 11 (23%) with cervical cancer, and one (2%) with vaginal cancer. The sites of ROMGC were the pelvic (46%), para-aortic (44%), supraclavicular (7%), mediastinal (4%), axillary (4%) lymph nodes and the lung (5.5%). Median total RT dose and fractionation were 62.1 Gy and 2.1 Gy/fraction; one patient was treated with SBRT. 32 patients (67%) received chemoradiation; these patients had higher rates of median DFS than those treated with RT alone (93 vs. 34 months, P = 0.05). At median follow-up of 11.7 years, 11 (23%) patients had progression of disease. 20 (42%) patients had died, 9 (19%) died from non-gynecologic cancer and 8 (17%) from gynecologic cancer (three were unknown). 25 (52%) patients were alive and disease-free (10 initially had endometrial cancer [63% of these patients], eight had cervical cancer [73%], six had ovarian cancer [30%], one had vaginal cancer [100%]). CONCLUSIONS: Long-term survival is possible for patients treated with definitive RT for ROMG, however randomized data are needed to identify which patients derive the most benefit.

Update on MRI in Evaluation and Treatment of Endometrial Cancer.

Endometrial cancer is the second most common gynecologic cancer worldwide and the most common gynecologic cancer in the United States, with an increasing incidence in high-income countries. Although the International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer is a surgical staging system, contemporary published evidence-based data and expert opinions recommend MRI for treatment planning as it provides critical diagnostic information on tumor size and depth, extent of myometrial and cervical invasion, extrauterine extent, and lymph node status, all of which are essential in choosing the most appropriate therapy. Multiparametric MRI using a combination of T2-weighted sequences, diffusion-weighted imaging, and multiphase contrast-enhanced imaging is the mainstay for imaging assessment of endometrial cancer. Identification of important prognostic factors at MRI improves both treatment selection and posttreatment follow-up. MRI also plays a crucial role for fertility-preserving strategies and in patients who are not surgical candidates by helping guide therapy and identify procedural complications. This review is a product of the Society of Abdominal Radiology Uterine and Ovarian Cancer Disease-Focused Panel and reflects a multidisciplinary international collaborative effort to summarize updated information highlighting the role of MRI for endometrial cancer depiction and delineation, treatment planning, and follow-up. The article includes information regarding dedicated MRI protocols, tips for MRI reporting, imaging pitfalls, and strategies for image quality optimization. The roles of MRI-guided radiation therapy, hybrid PET/MRI, and advanced MRI techniques that are applicable to endometrial cancer imaging are also discussed. Online supplemental material is available for this article. ©RSNA, 2022.

Early and Midtreatment Mortality in Palliative Radiotherapy: Emphasizing Patient Selection in High-Quality End-of-Life Care.

BACKGROUND: Palliative radiotherapy (RT) is effective, but some patients die during treatment or too soon afterward to experience benefit. This study investigates end-of-life RT patterns to inform shared decision-making and facilitate treatment consistent with palliative goals. MATERIALS AND METHODS: All patients who died ≤6 months after initiating palliative RT at an academic cancer center between 2015 and 2018 were identified. Associations with time-to-death, early mortality (≤30 days), and midtreatment mortality were analyzed. RESULTS: In total, 1,620 patients died ≤6 months from palliative RT initiation, including 574 (34%) deaths at ≤30 days and 222 (14%) midtreatment. Median survival was 43 days from RT start (95% CI, 41-45) and varied by site (P<.001), ranging from 36 (head and neck) to 53 days (dermal/soft tissue). On multivariable analysis, earlier time-to-death was associated with osseous (hazard ratio [HR], 1.33; P<.001) and head and neck (HR, 1.45; P<.001) sites, multiple RT courses ≤6 months (HR, 1.65; P<.001), and multisite treatments (HR, 1.40; P=.008), whereas stereotactic technique (HR, 0.77; P<.001) and more recent treatment year (HR, 0.82; P<.001) were associated with longer survival. No difference in time to death was noted among patients prescribed conventional RT in 1 to 10 versus >10 fractions (median, 40 vs 47 days; P=.272), although the latter entailed longer courses. The 30-day mortality group included 335 (58%) inpatients, who were 27% more likely to die midtreatment (P=.031). On multivariable analysis, midtreatment mortality among these inpatients was associated with thoracic (odds ratio [OR], 2.95; P=.002) and central nervous system (CNS; OR, 2.44; P=.002) indications, >5-fraction courses (OR, 3.27; P<.001), and performance status of 3 to 4 (OR, 1.63; P=.050). Conversely, palliative/supportive care consultation was associated with decreased midtreatment mortality (OR, 0.60; P=.045). CONCLUSIONS: Earlier referrals and hypofractionated courses (≤5-10 treatments) should be routinely considered for palliative RT indications, given the short life expectancies of patients at this stage in their disease course. Providers should exercise caution for emergent thoracic and CNS indications among inpatients with poor prognoses due to high midtreatment mortality.

A phase III study of transdermal granisetron versus oral ondansetron for women with gynecologic cancers receiving pelvic chemoradiation.

PURPOSE: To compare rates of complete response (no emesis, retching, or rescue antiemetics) in the late phase (days 4-7 post-chemotherapy) of cycle 1 between transdermal granisetron and oral ondansetron in cervical, endometrial, or vaginal cancer survivors undergoing chemoradiation at The University of Texas MD Anderson Cancer Center and LBJ Hospital in Houston, TX. METHODS: In this non-blinded parallel design trial, eligible patients received a granisetron patch replaced every 7 days or 8 mg of ondansetron thrice daily continued for 72 h after chemotherapy completion. Data were collected on medication compliance, episodes of chemotherapy-induced nausea and vomiting (CINV), use of rescue antiemetics, and effects of CINV on quality of life. RESULTS: Seventy-five survivors receiving chemoradiation for cervical (n = 61), endometrial (n = 12), or vaginal (n = 2) cancer were electronically randomized to transdermal granisetron (n = 41) or oral ondansetron (n = 34). In the late phase of cycle 1, the rate of complete response was 49.8% (95% CI, 35.2-64.3%) for transdermal granisetron and 39.7% (95% CI, 24.4-56.1%) for oral ondansetron. The posterior probability that transdermal granisetron achieved a higher success rate in controlling late-onset CINV compared with oral ondansetron was 82%. During the acute phase (day 1 post-chemotherapy) of cycles 2 and 3, transdermal granisetron patients used more rescue antiemetics than oral ondansetron patients (p = 0.006 and p = 0.003, respectively). Otherwise, no between-group differences in CINV events were observed. Medication compliance and the effect of CINV on quality of life were similar between groups. CONCLUSION: Transdermal granisetron was 82% more like to control CINV than oral ondansetron in the late phase of cycle 1 and performed similarly to oral ondansetron in all other cycles. Transdermal granisetron should be considered an option as prophylactic antiemetic therapy for gynecologic cancer survivors undergoing chemoradiation.

Pelvic fractures and changes in bone mineral density after radiotherapy for cervical, endometrial, and vaginal cancer: A prospective study of 239 women.

BACKGROUND: Advances in radiotherapy (RT) have led to improved oncologic outcomes for women with gynecologic cancers; however, the long-term effects and survivorship implications need further evaluation. The purpose of this study was to determine the incidence of pelvic fractures and changes in bone mineral density (BMD) after pelvic RT. METHODS: Two hundred thirty-nine women who had pelvic RT for cervical, endometrial, or vaginal cancer between 2008 and 2015 were prospectively studied. BMD scans and biomarkers of bone turnover were obtained at the baseline and 3 months, 1 year, and 2 years after RT. Imaging studies were assessed for pelvic fractures for up to 5 years. Patients with osteopenia, osteoporosis, or pelvic fractures at any point were referred to the endocrinology service for evaluation and treatment. RESULTS: The median age at diagnosis was 51 years; 132 patients (56%) were menopausal. The primary diagnoses were cervical (63.6%), endometrial (30.5%), and vaginal cancer (5.9%). Sixteen patients (7.8%; 95% confidence interval, 4.5%-12.4%) had pelvic fractures with actuarial rates of 3.6%, 12.7%, and 15.7% at 1, 2, and 3 years, respectively. Fractures were associated with baseline osteoporosis (P < .001), higher baseline bone-specific alkaline phosphatase (P < .001), and older age (P = .007). The proportion of patients with osteopenia/osteoporosis increased from 50% at the baseline to 58%, 59%, and 70% at 3 months, 1 year, and 2 years, respectively. CONCLUSIONS: A high proportion of women had significant decreases in BMD after pelvic RT, with 7.8% diagnosed with a pelvic fracture. BMD screening and pharmacologic intervention should be strongly considered for these high-risk women.

Radiation therapy for gynecologic malignancies during the COVID-19 pandemic: International expert consensus recommendations.

OBJECTIVE: To develop expert consensus recommendations regarding radiation therapy for gynecologic malignancies during the COVID-19 pandemic. METHODS: An international committee of ten experts in gynecologic radiation oncology convened to provide consensus recommendations for patients with gynecologic malignancies referred for radiation therapy. Treatment priority groups were established. A review of the relevant literature was performed and different clinical scenarios were categorized into three priority groups. For each stage and clinical scenario in cervical, endometrial, vulvar, vaginal and ovarian cancer, specific recommendations regarding dose, technique, and timing were provided by the panel. RESULTS: Expert review and discussion generated consensus recommendations to guide radiation oncologists treating gynecologic malignancies during the COVID-19 pandemic. Priority scales for cervical, endometrial, vulvar, vaginal, and ovarian cancers are presented. Both radical and palliative treatments are discussed. Management of COVID-19 positive patients is considered. Hypofractionated radiation therapy should be used when feasible and recommendations regarding radiation dose, timing, and technique have been provided for external beam and brachytherapy treatments. Concurrent chemotherapy may be limited in some countries, and consideration of radiation alone is recommended. CONCLUSIONS: The expert consensus recommendations provide guidance for delivering radiation therapy during the COVID-19 pandemic. Specific recommendations have been provided for common clinical scenarios encountered in gynecologic radiation oncology with a focus on strategies to reduce patient and staff exposure to COVID-19.

Tumor microbial diversity and compositional differences among women in Botswana with high-grade cervical dysplasia and cervical cancer.

INTRODUCTION: We characterized the cervical 16S rDNA microbiome of patients in Botswana with high-grade cervical dysplasia and locally advanced cervical cancer. METHODS: This prospective study included 31 patients: 21 with dysplasia and 10 with cancer. The Shannon diversity index was used to evaluate alpha (intra-sample) diversity, while the UniFrac (weighted and unweighted) and Bray-Curtis distances were employed to evaluate beta (inter-sample) diversity. The relative abundance of microbial taxa was compared among samples using linear discriminant analysis effect size. RESULTS: Alpha diversity was significantly higher in patients with cervical cancer than in patients with cervical dysplasia (P<0.05). Beta diversity also differed significantly (weighted UniFrac Bray-Curtis, P<0.01). Neither alpha diversity (P=0.8) nor beta diversity (P=0.19) varied by HIV status. The results of linear discriminant analysis effect size demonstrated that multiple taxa differed significantly between patients with cervical dysplasia vs cancer. Lachnospira bacteria (in the Clostridia class) were particularly enriched among cervical dysplasia patients, while Proteobacteria (members of the Firmicutes phyla and the Comamonadaceae family) were enriched in patients with cervical cancer. DISCUSSION: The results of our study suggest that differences exist in the diversity and composition of the cervical microbiota between patients with cervical dysplasia and patients with cervical cancer in Botswana. Additional studies are warranted to validate these findings and elucidate their clinical significance among women living in sub-Saharan Africa, as well as other regions of the world.

Brachytherapy: A critical component of primary radiation therapy for cervical cancer: From the Society of Gynecologic Oncology (SGO) and the American Brachytherapy Society (ABS).

Brachytherapy is well-established as an integral component in the standard of care for treatment of patients receiving primary radiotherapy for cervical cancer. A decline in brachytherapy has been associated with negative impacts on survival in the era of modern EBRT techniques. Conformal external beam therapies such intensity modulated radiation therapy (IMRT) or stereotactic body radiation therapy (SBRT) should not be used as alternatives to brachytherapy in patients undergoing primary curative-intent radiation therapy for cervical cancer. Computed tomography or magnetic resonance image-guided adaptive brachytherapy is evolving as the preferred brachytherapy method. With careful care coordination EBRT and brachytherapy can be successfully delivered at different treatment centers without compromising treatment time and outcome in areas where access to brachytherapy maybe limited.

Prognostic factors impacting survival in early stage uterine carcinosarcoma.

OBJECTIVE: Evaluate the impact of clinicopathologic characteristics and adjuvant treatment on survival outcomes in early stage uterine carcinosarcoma patients. METHODS: We performed a retrospective cohort study of women with stage I or II uterine carcinosarcoma at our institution between March 1990 and June 2016. All pathology had been reviewed and confirmed by gynecologic pathologists. Data were extracted from the electronic medical record. Descriptive and comparative statistics were used to compare clinicopathologic characteristics. Univariable and multivariable analyses were performed for survival outcomes. RESULTS: 140 patients were identified. Median age was 67 years (range: 36-91). Median follow-up was 39.1 months (2.9-297.4). The majority of patients had stage IA (67%) versus stage IB (21%) or stage II (11%) disease. The majority of patients (63%) received adjuvant treatment: vaginal brachytherapy only (14%); whole pelvic radiation therapy only (16%); chemotherapy only (n = 13, 9%); combination chemotherapy and vaginal brachytherapy (15%); combination chemotherapy and whole pelvic radiation (9%). 52 patients (37%) received no adjuvant therapy. Median overall survival (OS) was 48.0 months (95% CI 32.7-80.9). On multivariable analysis for OS, advancing age (HR 1.05, 95% CI 1.03-1.08, p < 0.001), higher stage (stage IB: HR 1.64, 95% CI 0.91-2.95, p = 0.10; stage II: HR 3.04, 95% CI 1.51-6.13, p = 0.002), and the presence of a rhabdomyosarcoma component (HR 1.66, 95% CI 1.02-2.70, p = 0.04) were significantly associated with worse OS. CONCLUSIONS: Advancing age, stage, and the presence of a rhabdomyosarcoma component were all associated with worse OS in patients with early stage uterine carcinosarcoma. New treatment algorithms should incorporate factors aside from stage alone.

National trends, outcomes, and costs of radiation therapy in the management of low- and high-intermediate risk endometrial cancer.

OBJECTIVE: To assess treatment patterns, outcomes, and costs for women with low-(LIR) and high-intermediate risk endometrial cancer (HIR) who are treated with and without adjuvant radiotherapy. METHODS: All patients with stage I endometrioid endometrial cancer who underwent surgery from 2000 to 2011 were identified from the SEER-Medicare database. LIR was defined as G1-2 tumors with <50% myometrial invasion or G3 with no invasion. HIR was defined as G1-2 tumors with ≥50% or G3 with <50% invasion. Patients were categorized according to whether they received adjuvant radiotherapy (vaginal brachytherapy [VBT], external beam radiotherapy [EBRT], or both) or no radiotherapy. Outcomes were analyzed and compared (primary outcome was overall survival). RESULTS: 10,842 patients met inclusion criteria. In the LIR group (n = 7609), there was no difference in 10-year overall survival between patients who received radiotherapy and those who did not (67% vs 65%, adjusted HR 0.95, 95% CI 0.81-1.11). In the HIR group (n = 3233), patients who underwent radiotherapy had a significant increase in survival (60% vs 47%, aHR 0.75, 95% CI 0.67-0.85). Radiotherapy was associated with increased costs compared to surgery alone ($26,585 vs $16,712, p < .001). Costs for patients receiving VBT, EBRT, and concurrent VBT/EBRT were $24,044, $27,512, and $31,564, respectively (p < .001). Radiotherapy was associated with an increased risk of gastrointestinal (7 vs 4%), genitourinary (2 vs 1%), and hematologic (16 vs 12%) complications (p < .001). CONCLUSIONS: Radiotherapy was associated with improved survival in women with HIR, but not in LIR. It also had increased costs and a higher morbidity risk. Consideration of observation without radiotherapy in LIR may be reasonable.

Adjuvant combined-modality therapy for stage IIIC endometrioid and non-endometrioid endometrial cancer.

OBJECTIVE: To identify the optimal adjuvant treatment regimen for patients with endometrioid and non-endometrioid node-positive endometrial cancer. METHODS: We retrospectively identified 249 women with FIGO 2009 stage IIIC endometrial cancer at our institution who underwent surgical staging from 1985 to 2015 followed by external beam radiotherapy (RT), chemotherapy (CT), or a combination of CT + RT. Survival rates were calculated using the Kaplan-Meier method. RESULTS: The 5-year disease-specific survival (DSS) rate for all patients was 65%. Adjuvant CT + RT conferred higher rates of 5-year DSS as compared to CT alone in patients with grade 3 endometrioid and non-endometrioid tumors (61% vs. 27%, P = 0.04 and 67% vs. 38%, P = 0.02, respectively). Among patients with non-endometrioid tumors, treatment with concurrent chemoradiotherapy followed by additional sequential chemotherapy had higher 5-year DSS rates than with concurrent chemoradiotherapy alone (74% vs. 50%, P = 0.02). The 3-year pelvic recurrence rate was 5% with RT ±â€¯CT and 35% with CT alone (P < 0.001) for all patients. No paraaortic nodal failures were observed following extended-field RT, but 14% of patients who received pelvic-only RT or CT alone developed recurrences in the paraaortic nodes (P < 0.001). CONCLUSIONS: Combined-modality therapy including adjuvant external beam pelvic radiotherapy yields excellent outcomes for patients with all subtypes of node-positive endometrial cancer. The most pronounced DSS advantage from adjuvant chemoradiotherapy was evident in women with non-endometrioid endometrial cancer.

Expanded validation of the EPIC bowel and urinary domains for use in women with gynecologic cancer undergoing postoperative radiotherapy.

OBJECTIVE: Women with endometrial or cervical cancer at risk for recurrence receive postoperative radiation therapy (RT). A patient reported outcomes (PRO) instrument to assess bowel and urinary toxicities is the Expanded Prostate Cancer Index Composite (EPIC), which has been validated in men with prostate cancer. As this instrument specifically measures bowel toxicity and the degree to which this is a problem, it was used in NRG Oncology/RTOG 1203 to compare intensity modulated RT (IMRT) to standard RT. This paper reports on the expanded validation of EPIC for use in women receiving pelvic RT. METHODS: In addition to the EPIC bowel domain, urinary toxicity (EPIC urinary domain), patient reported bowel toxicities (PRO-CTCAE) and quality of life (Functional Assessment of Cancer Therapy (FACT)) were completed before, during and after treatment. Sensitivity, reliability and concurrent validity were assessed. RESULTS: Mean bowel and urinary scores among 278 women enrolled were significantly worse during treatment and differed between groups. Acceptable to good reliability for bowel and urinary domain scores were obtained at all time points with the exception of one at baseline. Correlations between function and bother scores within the bowel and urinary domains were consistently stronger than those across domains. Correlations between bowel domain scores and PRO-CTCAE during treatment were stronger than those with the FACT. CONCLUSION: Correlations within and among the instruments indicate EPIC bowel and urinary domains are measuring conceptually discrete components of health. These EPIC domains are valid, reliable and sensitive instruments to measure PRO among women undergoing pelvic radiation.

MRI for Radiation Therapy Planning in Human Papillomavirus-associated Gynecologic Cancers.

Locally advanced human papillomavirus (HPV)-associated gynecologic cancers, including cervical, vaginal, and vulvar cancers, are treated primarily with radiation therapy (RT). Cervical cancer remains a leading cause of cancer death among women worldwide. The superior soft-tissue resolution of MRI compared with other imaging modalities makes it an ideal modality for RT planning, execution, and follow-up of these malignancies. This superiority has been corroborated in the literature when comparing MRI-based RT planning to radiography-based conventional treatment planning approaches. In 2005, the Groupe Européen de Curiethérapie and the European Society for Radiation Therapy and Oncology guidelines underscored the central role of MRI for successful implementation of three-dimensional image-based cervical cancer brachytherapy. The delineation of both gross tumor volume and clinical tumor volume for brachytherapy is performed at the time of each brachytherapy application, on the basis of the findings depicted on anatomic MR images. Contemporary knowledge concerning the role of MRI for RT planning in HPV-associated gynecologic cancers warrants an understanding of the epidemiology and clinical manifestations of these cancers, as well as knowledge of MRI protocol for cancer staging, selection of RT candidates, brachytherapy implant assessment, posttreatment surveillance, and delineation of treatment-related complications. Technical requirements, patient preparation, and image acquisition protocols are detailed in this review, and imaging-based treatment protocols are summarized. Knowledge of these fundamental concepts enables the radiologist to play an important role in diagnosis, staging, and posttreatment follow-up, helping to guide radiation oncologists and other clinicians in the management of these malignancies.©RSNA, 2019.

Effectiveness of definitive radiotherapy for squamous cell carcinoma of the vulva with gross inguinal lymphadenopathy.

OBJECTIVE: To evaluate the effectiveness and long-term side effects of definitive groin radiotherapy for vulvar cancer with grossly involved inguinal lymph nodes. METHODS: The records of 407 women with vulvar squamous cell carcinoma treated with radiotherapy at one institution during 1992-2014 were reviewed to identify patients who had radiographic or histologic evidence of grossly involved inguinal lymph nodes. Patients with lymphadenectomy before radiotherapy and patients treated for recurrent disease were excluded. Actuarial incidences of vulvar, inguinal, and distant recurrences, the relationship between vulvar recurrence and inguinal recurrence, and overall survival were analyzed using the Kaplan-Meier method. RESULTS: Thirty-three patients were identified. The median age at diagnosis was 64 years. The median long-axis radiographic diameter of the largest inguinal lymph node or lymph node mass was 2.5 cm (range, 1.4-8.7). Sixteen patients (48%) also had evidence of pelvic lymph node metastasis. The median radiation dose delivered to grossly involved nodes was 66.0 Gy (range, 60.0-70.0). The 3-year actuarial incidences of vulvar, groin, and distant recurrences were 24.2%, 17.7%, and 30.3%, respectively. With a median follow-up time of 28 months (range, 2-196), four patients (12%) had groin recurrence, of whom three also had vulvar recurrence. There were few major late adverse effects of regional radiotherapy. The 3-year overall survival rate was 51%. CONCLUSIONS: High-dose volume-directed radiotherapy achieves a high rate of local control with low risk of serious long-term toxic effects in patients with vulvar squamous cell carcinoma and grossly involved inguinal lymph nodes.

Outcomes and patterns of relapse after definitive radiation therapy for oligometastatic cervical cancer.

PURPOSE: Survival rates for women with metastatic cervical cancer are low, with limited management options. Definitive radiation therapy (RT) for oligometastatic disease has led to prolonged survival in other malignancies, but this approach has yet to be systematically studied for cervical cancer. METHODS AND MATERIALS: We evaluated 38 patients who received definitive RT to oligometastatic sites of cervical cancer at a single institution from 2002 to 2015. Patients presented with synchronous (n=9) or metachronous (n=15) oligometastatic disease to supraclavicular (SCV) nodes, or with recurrent disease in mediastinum (n=10) or lung (n=7). Three patients were treated for both SCV and mediastinal sites, and six patients were treated for para-aortic or pelvic recurrences along with oligometastatic sites. Most received chemotherapy: induction (n=5), concurrent (n=24), or adjuvant (n=5). Outcomes were evaluated via Kaplan-Meier, and associations were examined via Cox proportional hazards modeling. RESULTS: Median follow-up was 35.2months (range 3.1-94.7). Median overall survival (OS) was 50.7months from end of RT, with 2-year and 3-year OS rates of 74% and 65%. Median progression-free survival (PFS) was 21.7months, with 1-year and 2-year PFS rates of 63% and 48%. Of the 38 patients, 21 (55%) experienced progression, at a median time of 24.8months. There was one in-field failure. Other relapses occurred regionally (n=10) and distally (n=12), with two patients experiencing both. The most common site of recurrence following treatment of SCV disease was mediastinum (n=7). The incidence of grade≥3 toxicity from treatment of oligometastatic sites was <3%. CONCLUSIONS: Definitive RT to sites of oligometastatic cervical cancer can result in excellent local control, favorable outcomes, and even achieve long-term survival for carefully selected patients, with minimal RT-associated toxicity.

Role of Radiation Therapy in the Multidisciplinary Management of Uterine Carcinosarcoma.

OBJECTIVES: This study aimed to evaluate the impact of radiation therapy on outcomes for patients with uterine carcinosarcoma (UC). METHODS/MATERIALS: We retrospectively reviewed the records of 155 women with stage I (98), II (11), or III (46) UC who underwent total abdominal hysterectomy/bilateral salpingo-oophorectomy at our institution between 1990 and 2011. Survival rates were assessed using the Kaplan-Meier method and log-rank test. Univariate and multivariate Cox regression analyses were performed. RESULTS: Seventy-six patients (49%) received radiation therapy: 38 (50%) had vaginal cuff brachytherapy (VBT) alone and 38 had external beam radiation therapy (EBRT) ± VBT. Seventy patients (45%) received chemotherapy (12 concurrent, 49 adjuvant, 9 both). The 5-year overall survival rate was 48.6% (stage I, 53.8%; II, 30.0%; and III, 42.5%). The disease-specific survival (DSS) rate was 57.2% (stage I, 60.9%; II, 44.4%; and III, 51.8%). Patients treated with EBRT had a higher 5-year pelvic disease control rate (88.3%) than did patients treated with VBT only (67.4%) or no radiation (71.2%; P = 0.04). In stage III patients, EBRT was associated with higher 5-year pelvic disease control (90.0% vs 55.5%, P = 0.046), DSS (64.6% vs 46.4%, P = 0.13), and overall survival (64.6% vs 34.0%, P = 0.04) rates. For all 155 patients, age at least 65 years, cervical involvement, and lymph vascular space invasion were correlated with lower DSS on univariate and multivariate analyses. In addition, treatment with concurrent chemoradiation therapy was independently associated with a higher DSS rate on multivariate analysis. CONCLUSIONS: Patients with UC have a high rate of relapse in the regional nodes and distant sites. External beam radiation therapy improves locoregional control in all stages and may improve survival in stage III patients who are at the highest risk of pelvic relapse.

Perirenal Adiposity is Associated With Lower Progression-Free Survival From Ovarian Cancer.

OBJECTIVES: Abdominal obesity is linked with a higher risk of developing ovarian cancer. However, the link between abdominal obesity and survival after diagnosis of ovarian cancer is unknown. The purpose of this study was to determine the impact of abdominal obesity on progression-free survival in patients with ovarian cancer. METHODS: Among 258 patients, visceral and subcutaneous adipose tissue volume, along with perirenal adipose tissue thickness (a visceral adiposity proxy measure) was retrospectively measured from abdominal computed tomography (CT) scans obtained within 6 months of ovarian cancer diagnosis. Progression-free survival was computed using the Kaplan-Meier method and log-rank tests. Univariate and multivariate Cox proportional hazards analysis was used to determine relationships between measures of abdominal obesity and clinical variables in relation to progression-free survival. RESULTS: Patients with perirenal adipose tissue thickness greater than 5 mm(median) had lower rates of progression-free survival at 5 years compared with patients with perirenal adipose tissue thickness less than 5 mm (45.6% vs 53.8%, respectively). Perirenal adipose tissue thickness less than 5 mm was associated with lower rates of progression-free survival on multivariate analysis (hazard ratio = 1.37; 95% confidence interval, 1.03-1.82). There was no correlation with other metrics of abdominal adiposity on progression-free survival in univariate or multivariate analysis. CONCLUSIONS: Our data suggest that perirenal adipose, but not body mass index, visceral, or subcutaneous fat volume that were measured within 6 months from diagnosis, is associated with lower rates of progression-free survival in ovarian cancer.