Single-fraction radiation retreatment for bone metastases: role of a rapid access clinic.

OBJECTIVES: This study investigates retreatment rates in single-fraction radiation therapy (SFRT) for painful bone metastasis in patients with limited life expectancy. We compared retreatment-free survival (RFS) in patients from a rapid access bone metastases clinic (RABC) and non-RABC patients, identifying factors associated with retreatment. METHODS: In this observational study, we analysed RABC patients who received SFRT between April 2018 and November 2019, using non-RABC SFRT patients as a comparison group. Patients with prior or perioperative radiation therapy (RT) were excluded. The primary endpoint was same-site and any-site retreatment with RT or surgery. Patient characteristics were compared using χ2 and Student's t-tests, with RFS estimates based on a multistate model considering death as a competing risk using Aalen-Johansen estimates. RESULTS: We identified 151 patients (79 RABC, 72 non-RABC) with 225 treatments (102 RABC, 123 non-RABC) meeting eligibility criteria. Of the 22 (10.8%) same-site retreatments, 5 (22.7%) received surgery, 14 (63.6%) received RT and 3 (13.6%) received both RT and surgery. We found no significant differences in any-site RFS (p=0.97) or same-site RFS (p=0.11). CONCLUSIONS: RFS is high and similar comparable in the RABC and non-RABC cohorts. Retreatment rates are low, even in patients with low Eastern Cooperative Oncology Group scores.

The value of patient-reported outcomes to predict for symptom burden and health-related quality of life after chemoradiation for cervical cancer: A prospective study.

PURPOSE: Cervical cancer patients undergoing chemoradiation have high symptom burden. We performed an analysis of prospectively collected patient-reported outcomes(PROs) to determine characteristics predictive of poor treatment experience. METHODS: Between 2021-2023, we prospectively collected PROs from cervical cancer patients undergoing definitive chemoradiation. EORTC-QLQ-C30 and EORTC-QLQ-CX24 were completed at baseline(BL) and at the end of treatment(EOT). Poor treatment experience was defined as EOT poor health-related quality of life (HRQOL), low physical function, or significant overall symptom burden. Predictive factors analyzed included demographic, clinical, disease-specific factors, and baseline financial toxicity, depression, social function, and emotional function. ROC analysis provided appropriate predictive cut-off values. Univariable(UVA) and multivariable(MVA) linear regression analyses were performed. RESULTS: Fourty-nine patients completed BL and EOT questionnaires. Median age was 43 (range, 18-85). Most patients (59%) had stage III disease. Baseline financial toxicity ≥66.7, depression ≥66.7, social function ≤50 and emotional function ≤58 on the EORTC linear transformed scale of 0-100 were significant predictors for poor treatment experience (p≤0.04) based on ROC analysis. On MVA poor BL social function was associated with reduced EOT HRQOL (ß-9.3,_95%CI_-16.1_to_-2.6,_p<0.008), decreased physical function (ß-24.4,_95%CI_-36.3_to_-12.6,_p<0.001), and high symptom burden_(ß26.9,_95%CI_17.5_to_36.3,_p<0.001). Earlier disease stage predicted for decreased symptom burden_(ß-6.7,_95%CI_-13.1_to_-0.3,_p=0.039). BL financial toxicity was a significant predictor on UVA (p=0.001-0.044) and showed a significant interaction term on MVA (p=0.024-0.041) for all three domains of poor treatment experience. Demographic and treatment-related factors were not predictive. CONCLUSION: Cervical cancer patients with poor baseline social function or high financial toxicity were at-risk for increased symptom burden and poor HRQOL. Screening for these factors provides an opportunity for early intervention to improve treatment experience.

A Novel Positive-Contrast Magnetic Resonance Imaging Line Marker for High-Dose-Rate (HDR) MRI-Assisted Radiosurgery (MARS).

Magnetic resonance imaging (MRI) can facilitate accurate organ delineation and optimal dose distributions in high-dose-rate (HDR) MRI-Assisted Radiosurgery (MARS). Its use for this purpose has been limited by the lack of positive-contrast MRI markers that can clearly delineate the lumen of the HDR applicator and precisely show the path of the HDR source on T1- and T2-weighted MRI sequences. We investigated a novel MRI positive-contrast HDR brachytherapy or interventional radiotherapy line marker, C4:S, consisting of C4 (visible on T1-weighted images) complexed with saline. Longitudinal relaxation time (T1) and transverse relaxation time (T2) for C4:S were measured on a 1.5 T MRI scanner. High-density polyethylene (HDPE) tubing filled with C4:S as an HDR brachytherapy line marker was tested for visibility on T1- and T2-weighted MRI sequences in a tissue-equivalent female ultrasound training pelvis phantom. Relaxivity measurements indicated that C4:S solution had good T1-weighted contrast (relative to oil [fat] signal intensity) and good T2-weighted contrast (relative to water signal intensity) at both room temperature (relaxivity ratio > 1; r2/r1 = 1.43) and body temperature (relaxivity ratio > 1; r2/r1 = 1.38). These measurements were verified by the positive visualization of the C4:S (C4/saline 50:50) HDPE tube HDR brachytherapy line marker on both T1- and T2-weighted MRI sequences. Orientation did not affect the relaxivity of the C4:S contrast solution. C4:S encapsulated in HDPE tubing can be visualized as a positive line marker on both T1- and T2-weighted MRI sequences. MRI-guided HDR planning may be possible with these novel line markers for HDR MARS for several types of cancer.

Radiation Therapy With or Without Cisplatin for Local Recurrences of Endometrial Cancer: Results From an NRG Oncology/GOG Prospective Randomized Multicenter Clinical Trial.

PURPOSE: Pelvic recurrence is a frequent pattern of relapse for women with endometrial cancer. A randomized trial compared progression-free survival (PFS) after treatment with radiation therapy alone as compared with concurrent chemotherapy. MATERIALS AND METHODS: Between February 2008 and August 2020, 165 patients were randomly assigned 1:1 to receive either radiation treatment alone or a combination of chemotherapy and radiation treatment. The primary objective of this study was to determine whether chemoradiation therapy was more effective than radiation therapy alone at improving PFS. RESULTS: The majority of patients had low-grade (1 or 2) endometrioid histology (82%) and recurrences confined to the vagina (86%). External beam with either the three-dimensional or intensity modulated radiation treatment technique was followed by a boost delivered with brachytherapy or external beam. Patients randomly assigned to receive chemotherapy were treated with once weekly cisplatin (40 mg/m2). Rates of acute toxicity were higher in patients treated with chemoradiation as compared with radiation treatment alone. Median PFS was longer for patients treated with radiation therapy alone as compared with chemotherapy and radiation (median PFS was not reached for RT v 73 months for chemoradiation, hazard ratio of 1.25 (95% CI, 0.75 to 2.07). At 3 years, 73% of patients treated definitively with radiation and 62% of patients treated with chemoradiation were alive and free of disease progression. CONCLUSION: Excellent outcomes can be achieved for women with localized recurrences of endometrial cancer when treated with radiation therapy. The addition of chemotherapy does not improve PFS for patients treated with definitive radiation therapy for recurrent endometrial cancer and increases acute toxicity. Patients with low-grade and vaginal recurrences who constituted the majority of those enrolled are best treated with radiation therapy alone.

Disease progression, survival, and molecular disparities in Black and White patients with endometrioid endometrial carcinoma in real-world registries and GOG/NRG oncology randomized phase III clinical trials.

OBJECTIVE: Investigate racial disparities in outcomes and molecular features in Black and White patients with endometrioid endometrial carcinoma (EEC). METHODS: Black and White patients diagnosed with EEC who underwent hysterectomy ± adjuvant treatment in SEER, National Cancer Database (NCDB), the Genomics Evidence Neoplasia Information Exchange (GENIE) project (v.13.0), and eight NCI-sponsored randomized phase III clinical trials (RCTs) were studied. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for cancer-related death (CRD), non-cancer death (NCD), and all-cause death. RESULTS: Black (n = 4397) vs. White (n = 47,959) patients in SEER had a HR (95% CI) of 2.04 (1.87-2.23) for CRD and 1.22 (1.09-1.36) for NCD. In NCDB, the HR (95% CI) for death in Black (n = 13,468) vs. White (n = 155,706) patients was 1.52 (1.46-1.58) dropping to 1.29 (1.23-1.36) after propensity-score matching for age, comorbidity, income, insurance, grade, stage, LVSI, and treatment. In GENIE, Black (n = 109) vs. White (n = 1780) patients had fewer PTEN, PIK3R1, FBXW7, NF1, mTOR, CCND1, and PI3K-pathway-related gene mutations. In contrast, TP53 and DNA-repair-related gene mutation frequency as well as tumor mutational burden-high status were similar in Black and White patients. In RCTs, Black (n = 187) vs. White (n = 2877) patients were more likely to have advanced or recurrent disease, higher grade, worse performance status and progressive disease. Risk of death in Black vs. White patients in RCTs was 2.19 (1.77-2.71) persisting to 1.32 (1.09-1.61) after matching for grade, stage, and treatment arm while balancing age and performance status. CONCLUSIONS: Differences exist in clinical presentation, outcomes, and molecular features in Black vs. White patients with EEC in real-world registries and RCTs. Targeted-drug development, strategies to modify social determinants, and diverse inclusion in RCTs are approaches to reduce disparities.

Immuno-Molecular Targeted Therapy Use and Survival Benefit in Patients with Stage IVB Cervical Carcinoma in Commission on Cancer®-Accredited Facilities in the United States.

PURPOSE: To investigate IMT use and survival in real-world stage IVB cervical cancer patients outside randomized clinical trials. METHODS: Patients diagnosed with stage IVB cervical cancer during 2013-2019 in the National Cancer Database and treated with chemotherapy (CT) ± external beam radiation (EBRT) ± intracavitary brachytherapy (ICBT) ± IMT were studied. The adjusted hazard ratio (AHR) and 95% confidence interval (CI) for risk of death were estimated in patients treated with vs. without IMT after applying propensity score analysis to balance the clinical covariates. RESULTS: There were 3164 evaluable patients, including 969 (31%) who were treated with IMT. The use of IMT increased from 11% in 2013 to 46% in 2019. Age, insurance, facility type, sites of distant metastasis, and type of first-line treatment were independently associated with using IMT. In propensity-score-balanced patients, the median survival was 18.6 vs. 13.1 months for with vs. without IMT (p < 0.001). The AHR was 0.72 (95% CI = 0.64-0.80) for adding IMT overall, 0.72 for IMT + CT, 0.66 for IMT + CT + EBRT, and 0.69 for IMT + CT + EBRT + ICBT. IMT-associated survival improvements were suggested in all subgroups by age, race/ethnicity, comorbidity score, facility type, tumor grade, tumor size, and site of metastasis. CONCLUSIONS: IMT was associated with a consistent survival benefit in real-world patients with stage IVB cervical cancer.

Survival disparities in non-Hispanic Black and White cervical cancer patients vary by histology and are largely explained by modifiable factors.

PURPOSE: We investigated racial disparities in survival by histology in cervical cancer and examined the factors contributing to these disparities. METHODS: Non-Hispanic Black and non-Hispanic White (hereafter known as Black and White) patients with stage I-IV cervical carcinoma diagnosed between 2004 and 2017 in the National Cancer Database were studied. Survival differences were compared using Cox modeling to estimate hazard ratio (HR) or adjusted HR (AHR) and 95% confidence interval (CI). The contribution of demographic, socioeconomic and clinical factors to the Black vs White differences in survival was estimated after applying propensity score weighting in patients with squamous cell carcinoma (SCC) or adenocarcinoma (AC). RESULTS: This study included 10,111 Black and 43,252 White patients with cervical cancer. Black patients had worse survival than White cervical cancer patients (HR = 1.40, 95% CI = 1.35-1.45). Survival disparities between Black and White patients varied significantly by histology (HR = 1.20, 95% CI = 1.15-1.24 for SCC; HR = 2.32, 95% CI = 2.12-2.54 for AC, interaction p < 0.0001). After balancing the selected demographic, socioeconomic and clinical factors, survival in Black vs. White patients was no longer different in those with SCC (AHR = 1.01, 95% CI 0.97-1.06) or AC (AHR = 1.09, 95% CI = 0.96-1.24). In SCC, the largest contributors to survival disparities were neighborhood income and insurance. In AC, age was the most significant contributor followed by neighborhood income, insurance, and stage. Diagnosis of AC (but not SCC) at ≥65 years old was more common in Black vs. White patients (26% vs. 13%, respectively). CONCLUSIONS: Histology matters in survival disparities and diagnosis at ≥65 years old between Black and White cervical cancer patients. These disparities were largely explained by modifiable factors.

Comparing long-term sexual dysfunction across different uterine cancer treatment modalities.

INTRODUCTION: The objective of this study was to assess differences in long-term sexual and menopausal side effects after uterine cancer treatment among treatment modalities. METHODS AND MATERIALS: This is a cross-sectional study that examined women treated for uterine cancer from 2006-2018. Eligible women included those who underwent a hysterectomy/bilateral salpino-oophorectemy alone (HS), with brachytherapy (BT), or with external beam radiation therapy (EBRT). A noncancer cohort of women who underwent a hysterectomy/BSO for benign indications were also identified (non-CA). To compare outcomes, we utilized a shortened form of the female sexual function index (FSFI) and the menopause survey, which consists of 3 subscales: hot flashes, vaginal symptoms, and urinary symptoms. Demographic, comorbidity, and other treatment variables were collected. Survey totals were compared across cohorts using ANOVA tests and logistic regression. RESULTS: A total of 284 women completed the Menopause Survey (Non-CA 64, HS 60, BT 69, EBRT 91); 116 women reported sexual activity in the last 4 weeks and completed the FSFI (NC 32, HS 21, BT 31, EBRT 32). The mean FSFI score for the entire cohort was 11.4 (SD 4.16), which indicates poor sexual function. There was no significant difference between any cohort in the overall FSFI score (p = 0.708) or in any of the FSFI subscales (all p > 0.05). On univariate analysis, BT was associated with fewer menopausal hot flashes and vaginal symptoms compared to the non-CA cohort (p < 0.05), which did not persist on multivariable analysis. CONCLUSION: There was no significant difference in sexual dysfunction or menopausal symptoms in those treated for uterine cancer with or without adjuvant radiation. Most patients reported poor sexual function.

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.

Exploratory analysis of the cervix tumoral HPV antigen-specific T-cell repertoire during chemoradiation and after brachytherapy.

BACKGROUND: Chemoradiation (CRT) may modulate the immune milieu as an in-situ vaccine. Rapid dose delivery of brachytherapy has unclear impact on T-cell repertoires. HPV-associated cancers express viral oncoproteins E6/E7, which enable tracking antigen/tumor-specific immunity during CRT. METHODS: Thirteen cervical cancer patients on a multi-institutional prospective protocol from 1/2020-1/2023 underwent standard-of-care CRT with pulsed-dose-rate brachytherapy boost (2 fractions). Cervix swabs at various timepoints underwent multiplex DNA deep sequencing of the TCR-ß/CDR3 region with immunoSEQ. Separately, HPV-responsive T-cell clones were also expanded ex vivo. Statistical analysis was via Mann-Whitney-U. RESULTS: TCR productive clonality, templates, frequency, or rearrangements increased post-brachytherapy in 8 patients. Seven patients had E6/E7-responsive evolution over CRT with increased productive templates (ranges: 1.2-50.2 fold-increase from baseline), frequency (1.2-1.7), rearrangements (1.2-40.2), and clonality (1.2-15.4). Five patients had HPV-responsive clonal expansion post-brachytherapy, without changes in HPV non-responsive clones. Epitope mapping revealed VDJ rearrangements targeting cervical cancer-associated antigens in 5 patients. The only two patients with disease recurrence lacked response in all metrics. A lack of global TCR remodeling correlated with worse recurrence-free survival, p = 0.04. CONCLUSION: CRT and brachytherapy alters the cervical cancer microenvironment to facilitate the expansion of specific T-cell populations, which may contribute to treatment efficacy.

Tumor-resident Lactobacillus iners confer chemoradiation resistance through lactate-induced metabolic rewiring.

Tumor microbiota can produce active metabolites that affect cancer and immune cell signaling, metabolism, and proliferation. Here, we explore tumor and gut microbiome features that affect chemoradiation response in patients with cervical cancer using a combined approach of deep microbiome sequencing, targeted bacterial culture, and in vitro assays. We identify that an obligate L-lactate-producing lactic acid bacterium found in tumors, Lactobacillus iners, is associated with decreased survival in patients, induces chemotherapy and radiation resistance in cervical cancer cells, and leads to metabolic rewiring, or alterations in multiple metabolic pathways, in tumors. Genomically similar L-lactate-producing lactic acid bacteria commensal to other body sites are also significantly associated with survival in colorectal, lung, head and neck, and skin cancers. Our findings demonstrate that lactic acid bacteria in the tumor microenvironment can alter tumor metabolism and lactate signaling pathways, causing therapeutic resistance. Lactic acid bacteria could be promising therapeutic targets across cancer types.

Stereotactic Body Radiation Therapy for Gynecologic Malignancies: A Case-Based Radiosurgery Society Practice Review.

PURPOSE: The use of stereotactic body radiation therapy (SBRT) for gynecologic malignancies is controversial. We discuss certain circumstances when highly precise SBRT may be a useful tool to consider in the management of selected patients. METHODS AND MATERIALS: Case selection included the following scenarios, the first 2 with palliative intent, para-aortic nodal oligorecurrence of ovarian cancer, pelvic sidewall oligorecurrence of cervical cancer, and inoperable endometrial cancer boost after intensity modulated radiation to the pelvis treated with curative intent. Patient characteristics, fractionation, prescription dose, treatment technique, and dose constraints were discussed. Relevant literature to these cases was summarized to provide a framework for treatment of similar patients. RESULTS: Treatment of gynecologic malignancies with SBRT requires many considerations, including treatment intent, optimal patient selection, fractionation selection, tumor localization, and plan optimization. Although other treatment paradigms including conventionally fractionated radiation therapy and brachytherapy remain the standard-of-care for definitive treatment of gynecologic malignancies, SBRT may have a role in palliative cases or those where high doses are not required due to the unacceptable toxicity that may occur with SBRT. CONCLUSIONS: A case-based practice review was developed by the Radiosurgery Society to provide a practical guide to the common scenarios noted above affecting patients with gynecologic malignancies.

Identifying the optimal deep learning architecture and parameters for automatic beam aperture definition in 3D radiotherapy.

PURPOSE: Two-dimensional radiotherapy is often used to treat cervical cancer in low- and middle-income countries, but treatment planning can be challenging and time-consuming. Neural networks offer the potential to greatly decrease planning time through automation, but the impact of the wide range of hyperparameters to be set during training on model accuracy has not been exhaustively investigated. In the current study, we evaluated the effect of several convolutional neural network architectures and hyperparameters on 2D radiotherapy treatment field delineation. METHODS: Six commonly used deep learning architectures were trained to delineate four-field box apertures on digitally reconstructed radiographs for cervical cancer radiotherapy. A comprehensive search of optimal hyperparameters for all models was conducted by varying the initial learning rate, image normalization methods, and (when appropriate) convolutional kernel size, the number of learnable parameters via network depth and the number of feature maps per convolution, and nonlinear activation functions. This yielded over 1700 unique models, which were all trained until performance converged and then tested on a separate dataset. RESULTS: Of all hyperparameters, the choice of initial learning rate was most consistently significant for improved performance on the test set, with all top-performing models using learning rates of 0.0001. The optimal image normalization was not consistent across architectures. High overlap (mean Dice similarity coefficient = 0.98) and surface distance agreement (mean surface distance < 2 mm) were achieved between the treatment field apertures for all architectures using the identified best hyperparameters. Overlap Dice similarity coefficient (DSC) and distance metrics (mean surface distance and Hausdorff distance) indicated that DeepLabv3+ and D-LinkNet architectures were least sensitive to initial hyperparameter selection. CONCLUSION: DeepLabv3+ and D-LinkNet are most robust to initial hyperparameter selection. Learning rate, nonlinear activation function, and kernel size are also important hyperparameters for improving performance.

Feasibility of quantitative diffusion-weighted imaging during intra-procedural MRI-guided brachytherapy of locally advanced cervical and vaginal cancers.

PURPOSE: To determine the feasibility of quantitative apparent diffusion coefficient (ADC) acquisition during magnetic resonance imaging-guided brachytherapy (MRgBT) using reduced field-of-view (rFOV) diffusion-weighted imaging (DWI). METHODS AND MATERIALS: T2-weighted (T2w) MR and full-FOV single-shot echo planar (ssEPI) DWI were acquired in 7 patients with cervical or vaginal malignancy at baseline and prior to brachytherapy, while rFOV-DWI was acquired during MRgBT following brachytherapy applicator placement. The gross target volume (GTV) was contoured on the T2w images and registered to the ADC map. Voxels at the GTV's maximum Maurer distance comprised a central sub-volume (GTVcenter). Contour ADC mean and standard deviation were compared between timepoints using repeated measures ANOVA. RESULTS: ssEPI-DWI mean ADC increased between baseline and prebrachytherapy from 1.03 ± 0.18 10-3 mm2/s to 1.34 ± 0.28 10-3 mm2/s for the GTV (p = 0.06) and from 0.84 ± 0.13 10-3 mm2/s to 1.26 ± 0.25 10-3 mm2/s at the level of the GTVcenter (p = 0.03), consistent with early treatment response. rFOV-DWI during MRgBT demonstrated mean ADC values of 1.28 ± 0.14 10-3 mm2/s and 1.28 ± 0.19 10-3 mm2/s for the GTV and GTVcenter, respectively (p = 0.02 and p = 0.03 relative to baseline). No significant differences were observed between ssEPI-DWI and rFOV-DWI ADC measurements. CONCLUSIONS: Quantitative ADC measurement in the setting of MRI guided brachytherapy implant placement for cervical and vaginal cancers is feasible using rFOV-DWI, with comparable mean ADC comparable to prebrachytherapy ssEPI-DWI, and may enable MRI-guided radiotherapy targeting of low ADC, radiation resistant sub-volumes of tumor.

Patient Reported Outcomes for Women Undergoing Definitive Chemoradiation for Gynecologic Cancer: A Prospective Clinical Trial.

PURPOSE: Patients with gynecologic malignancies have high psychosocial and symptom burden. We report data from a prospective trial evaluating patient-reported outcome (PRO) metrics in women undergoing definitive chemoradiation with brachytherapy (BT). METHODS AND MATERIALS: A single-institution prospective trial evaluating outcomes of gynecologic cancer patients undergoing BT. Questionnaires to assess PROs at baseline, post-BT, and 60-day follow-up were collected, using European Organization for Research and Treatment of Cancer-Quality of Life Question-Core 30 and European Organization for Research and Treatment of Cancer-Quality of Life Question-Cervical Cancer Module validated metrics. Higher scores for functional scales/global health and lower scores for symptom items are favorable. European Organization for Research and Treatment of Cancer-Quality of Life Question-Core 30 mean scores were compared with a reference population. When comparing the study population between time points, medians, interquartile range, and nonparametric testing were used. RESULTS: Thirty-three patients were enrolled, and 29 (88%) completed baseline PRO metrics. Mean global health score was worse than the reference population of women with any cancer diagnosis at baseline (41 vs 59, P < .001) and decreased further at follow-up (42 vs 33, P = .005). Compared with the cervical cancer reference, our patients had significantly worse social function (62 vs 83, P = .03), financial toxicity (49 vs 10, P < .001), fatigue (49 vs 34, P = .04), nausea/vomiting (26 vs 9, P = .001), and appetite loss (36 vs 16, P = .004).The majority of patients described depression (53%), feeling less attractive (64%), life interference (66%), and/or worry (69%). At baseline, higher global health scores were associated with improved physical functioning (R20.58, P < .001), social functioning (R20.56, P < .001), and body image (R20.40, P < .001); lower scores with more symptom burden (R20.71, P < .001), financial toxicity (R20.50, P < .001), and/or sexual worry (R20.25, P = .001). CONCLUSIONS: Patients with cervical cancer have significant symptom burden and psychosocial toxicity, contributing to decreased quality of life. These data highlight the need for improved support throughout treatment for this high-risk population.

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.

Image-Guided Radiotherapy for Gynecologic Malignancies: What the Radiologist Needs to Know.

Pelvic imaging is integral to contemporary radiotherapy (RT) management of gynecologic malignancies. For cervical, endometrial, vulvar, and vaginal cancers, three-dimensional imaging modalities aid in tumor staging and RT candidate selection and inform treatment strategy, including RT planning, execution, and posttherapy surveillance. State-of-the-art care routinely incorporates magnetic resonance (MR) imaging, 18F-fluorodeoxyglucose-PET/computed tomography (CT), and CT to guide external beam RT and brachytherapy, allowing the customization of RT plans to maximize patient outcomes and reduce treatment-related toxicities. Follow-up imaging identifies radiation-resistant and recurrent disease as well as short-term and long-term toxicities from RT.

HPV-related anal cancer is associated with changes in the anorectal microbiome during cancer development.

Background: Squamous cell carcinoma of the anus (SCCA) is a rare gastrointestinal cancer. Factors associated with progression of HPV infection to anal dysplasia and cancer are unclear and screening guidelines and approaches for anal dysplasia are less clear than for cervical dysplasia. One potential contributing factor is the anorectal microbiome. In this study, we aimed to identify differences in anal microbiome composition in the settings of HPV infection, anal dysplasia, and anal cancer in this rare disease. Methods: Patients were enrolled in two prospective studies. Patients with anal dysplasia were part of a cross-sectional cohort that enrolled women with high-grade lower genital tract dysplasia. Anorectal tumor swabs were prospectively collected from patients with biopsy-confirmed locally advanced SCCA prior to receiving standard-of-care chemoradiotherapy (CRT). Patients with high-grade lower genital tract dysplasia without anal dysplasia were considered high-risk (HR Normal). 16S V4 rRNA Microbiome sequencing was performed for anal swabs. Alpha and Beta Diversity and composition were compared for HR Normal, anal dysplasia, and anal cancer. Results: 60 patients with high-grade lower genital tract dysplasia were initially enrolled. Seven patients had concurrent anal dysplasia and 44 patients were considered HR Normal. Anorectal swabs from 21 patients with localized SCCA were included, sequenced, and analyzed in the study. Analysis of weighted and unweighted UniFrac distances demonstrated significant differences in microbial community composition between anal cancer and HR normal (p=0.018). LEfSe identified that all three groups exhibited differential enrichment of specific taxa. Peptoniphilus (p=0.028), Fusobacteria (p=0.0295), Porphyromonas (p=0.034), and Prevotella (p=0.029) were enriched in anal cancer specimens when compared to HR normal. Conclusion: Although alpha diversity was similar between HR Normal, dysplasia and cancer patients, composition differed significantly between the three groups. Increased anorectal Peptoniphilus, Fusobacteria, Porphyromonas, and Prevotella abundance were associated with anal cancer. These organisms have been reported in various gastrointestinal cancers with roles in facilitating the proinflammatory microenvironment and neoplasia progression. Future work should investigate a potential role of microbiome analysis in screening for anal dysplasia and investigation into potential mechanisms of how these microbial imbalances influence the immune system and anal carcinogenesis.