The Value of Patient-Reported Outcomes to Predict Symptom Burden and Health-Related Quality of Life After Chemoradiation for Cervical Cancer: A Prospective Study.

PURPOSE: Patients with cervical cancer undergoing chemoradiation have high symptom burden. We performed an analysis of prospectively collected data on patient-reported outcomes to determine characteristics predictive of poor treatment experience. METHODS AND MATERIALS: Between 2021 and 2023, we prospectively collected data on patient-reported outcomes from patients with cervical cancer undergoing definitive chemoradiation. The European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Question-Core 30 and the EORTC-Quality of Life Question-Cervical Cancer module 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, and disease-specific factors and BL financial toxicity, depression, social function, and emotional function. Receiver operating characteristic analysis provided appropriate predictive cutoff values. Univariable and multivariable (MVA) linear regression analyses were performed. RESULTS: Forty-nine patients completed BL and EOT questionnaires. Median age was 43 years (range, 18-85 years). Most patients (59%) had stage III disease. BL financial toxicity ≥66.7, depression ≥66.7, social function ≤50, and emotional function ≤58 on the EORTC linear transformed scale of 0 to 100 were significant predictors for poor treatment experience (p ≤ .04) based on receiver operating characteristic analysis. On MVA, poor BL social function was associated with reduced EOT HRQOL (ß, -9.3; 95% CI, -16.1 to -2.6; p < .008), decreased physical function (ß, -24.4; 95% CI, -36.3 to -12.6; p < .001), and high symptom burden (ß, 26.9; 95% CI, 17.5-36.3; p < .001). Earlier disease stage predicted decreased symptom burden (ß, -6.7; 95% CI, -13.1 to -0.3; p = .039). BL financial toxicity was a significant predictor in univariable analysis (p = .001-.044) and showed a significant interaction term on MVA (p = .024-.041) for all 3 domains of poor treatment experience. Demographic and treatment-related factors were not predictive. CONCLUSIONS: Patients with cervical cancer with poor BL 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.

Endoscopic assessment of radiological stage IVA cervical cancer: A bivariate meta-analysis supporting an evidence-based staging algorithm proposal.

OBJECTIVE: To optimize the use of confirmatory endoscopic exams (cystoscopy/proctoscopy) in the staging of locally advanced cervical cancer (LACC), the present study evaluates the predictive value of radiological exams (CT and MRI) to detect bladder/rectum invasion. METHODS: A systematic search of databases (PubMed and EMBASE) was performed (CRD42021270329). The inclusion criteria were: a) cervix cancer diagnosis; b) staging CT and/or MRI (index test); c) staging cystoscopy and/or proctoscopy (standard test); and d) numbers of true positives (TP), true negatives (TN), false positives (FP), and false negatives (FN) provided. A random-effects bivariate meta-analysis of positive predictive value (PPV) and negative predictive value (NPV) was performed with moderator analyses by imaging modality (CT and MRI) and prevalence. RESULTS: Nineteen studies met the inclusion criteria, totaling 3480 and 1641 patients for bladder and rectum analyses, respectively. For bladder invasion (prevalence ranged from 0.9% to 34.5%), the overall PPV was 45% (95% confidence interval, 33%-57%, based on 19 studies). Per subgroup, the PPV was 31% for MRI/prevalence ≤6%, 33% for CT/prevalence ≤6%, and 69% for CT/prevalence >6%. For rectal invasion (prevalence ranged from 0.4% to 20.0%), the overall PPV was 30% (95% confidence interval, 17%-47%, based on 8 studies). Per subgroup, the PPV was 36% for MRI/prevalence ≤1%, 17% for MRI/prevalence >1%, and 38% for CT/prevalence >1%. The overall NPV for bladder invasion and rectal invasion were 98% (95% confidence interval, 97%-99%) and 100% (95% confidence interval, 99%-100%), respectively. Considering prevalence and radiological modality, the point estimate of NPV varied from 95% to 100% for bladder invasion and from 99% to 100% for rectum invasion. CONCLUSIONS: Due to low PPV (<50%) of radiological staging, endoscopic exams may be necessary to correctly assess radiological stage IVA LACC. However, they are not necessary after negative radiological exam (NPV ≥95%).

Radiation Sciences Education in Africa: An Assessment of Current Training Practices and Evaluation of a High-Yield Course in Radiation Biology and Radiation Physics.

PURPOSE: Formal education in the radiation sciences is critical for the safe and effective delivery of radiotherapy. Practices and patterns of radiation sciences education and trainee performance in the radiation sciences are poorly described. This study assesses the current state of radiation sciences education in Africa and evaluates a high-yield, on-site educational program in radiation biology and radiation physics for oncology and radiation therapy trainees in Africa. METHODS: An anonymous survey was distributed to members of the African Organization for Research and Treatment in Cancer Training Interest Group to assess current attitudes and practices toward radiation sciences education. A 2-week, on-site educational course in radiation biology and radiation physics was conducted at the Cancer Diseases Hospital in Lusaka, Zambia. Pre- and postcourse assessments in both disciplines were administered to gauge the effectiveness of an intensive high-yield course in the radiation sciences. RESULTS: Significant deficiencies were identified in radiation sciences education, especially in radiation biology. Lack of expert instructors in radiation biology was reported by half of all respondents and was the major contributing factor to deficient education in the radiation sciences. The educational course resulted in marked improvements in radiation biology assessment scores (median pre- and posttest scores, 27% and 55%, respectively; P < .0001) and radiation physics assessment scores (median pre- and posttest scores, 30% and 57.5%, respectively; P < .0001). CONCLUSION: Radiation sciences education in African oncology training programs is inadequate. International collaboration between expert radiation biology and radiation physics instructors can address this educational deficiency and improve trainee competence in the foundational radiation sciences that is critical for the safe and effective delivery of radiotherapy.

Clinical utility and value contribution of an MRI-positive line marker for image-guided brachytherapy in gynecologic malignancies.

PURPOSE: The purpose of this study was to investigate the utility of a novel MRI-positive line marker, composed of C4:S (cobalt chloride-based contrast agent) encapsulated in high-density polyethylene tubing, in permitting dosimetry and treatment planning directly on MRI. METHODS AND MATERIALS: We evaluated the clinical feasibility of the C4:S line markers in nine sequential brachytherapy procedures for gynecologic malignancies, including six tandem-and-ovoid and three interstitial cases. We then quantified the internal resource utilization of an intraoperative MRI-guided procedural episode via time-driven activity-based costing, identifying opportunities for cost-containment with use of the C4:S line markers. RESULTS: The C4:S line markers demonstrated the strongest positive signal visibility on 3D constructive interference in steady state (CISS)/FIESTA-C followed by T1-weighted sequences, permitting accurate delineation of the applicator lumen and thus the source path. These images may be fused along with traditional T2-weighted sequences for optimal tumor and anatomy contouring, followed by treatment planning directly on MRI. By eliminating postoperative CT for fusion and applicator registration from the procedural episode, use of the C4:S line markers could decrease workflow time and lower total delivery costs per procedure. CONCLUSIONS: This analysis supports the clinical utility and value contribution of the C4:S line markers, which permit accurate MRI-based dosimetry and treatment planning, thereby eliminating the need for postoperative CT for fusion and applicator registration.

Developing an intraoperative 3T MRI-guided brachytherapy program within a diagnostic imaging suite: Methods, process workflow, and value-based analysis.

PURPOSE: We integrated a brachytherapy procedural workflow within an existing diagnostic 3.0-T (3T) MRI suite. This setup facilitates intraoperative MRI guidance for optimal applicator positioning, particularly for interstitial needle placements in gynecologic cases with extensive parametrial involvement. METHODS AND MATERIALS: Here we summarize the multidisciplinary collaboration, equipment, and supplies necessary to implement an intraoperative MRI-guided brachytherapy program; outline the operational workflow via process maps; and address safety precautions. We evaluate internal resource utilization associated with this progressive approach via time-driven activity-based costing methodology, comparing institutional costs to that of a traditional workflow (within a CT suite, followed by separate postprocedure MRI) over a single brachytherapy procedural episode. RESULTS: Resource utilization was only 15% higher for the intraoperative MRI-based workflow, attributable to use of the MRI suite and increased radiologist effort. Personnel expenses were the greatest cost drivers for either workflow, accounting for 76-77% of total resource utilization. However, use of the MRI suite allows for potential cost-shifting opportunities from other resources, such as CT, during the procedural episode. Improvements in process speed can also decrease costs: for each 10% decrease in case duration from baseline procedure time, total costs could decrease by roughly 8%. CONCLUSIONS: This analysis supports the feasibility of an intraoperative MRI-guided brachytherapy program within a diagnostic MRI suite and defines many of the resources required for this procedural workflow. Longer followup will define the full utility of this approach in optimizing the therapeutic ratio for gynecologic cancers, which may translate into lower costs and higher value with time, over a full cycle of care.

Quantifying institutional resource utilization of adjuvant brachytherapy and intensity-modulated radiation therapy for endometrial cancer via time-driven activity-based costing.

PURPOSE: The purpose of this study was to quantify the cost of resources required to deliver adjuvant radiation therapy (RT) for high- to intermediate-risk endometrial cancer using time-driven activity-based costing (TDABC). METHODS AND MATERIALS: Comparisons were made for three and five fractions of vaginal cuff brachytherapy (VCB), 28 fractions of intensity-modulated radiation therapy (IMRT), and combined modality RT (25-fraction IMRT followed by 2-fraction VCB). Process maps were developed representing each phase of care. Salary and equipment costs were obtained to derive capacity cost rates, which were multiplied by process times and summed to calculate total costs. Costs were compared with 2018 Medicare physician fee schedule reimbursement. RESULTS: Full cycle costs for 5-fraction VCB, IMRT, and combined modality RT were 42%, 61%, and 93% higher, respectively, than for 3-fraction VCB. Differences were attributable to course duration and number of fractions/visits. Accumulation of cost throughout the cycle was steeper for VCB, rising rapidly within a shorter time frame. Personnel cost was the greatest driver for all modalities, constituting 76% and 71% of costs for IMRT and VCB, respectively, with VCB requiring 74% more physicist time. Total reimbursement for 5-fraction VCB was 40% higher than for 3-fractions. Professional reimbursement for IMRT was 31% higher than for 5-fraction VCB, vs. IMRT requiring 43% more physician TDABC than 5-fraction VCB. CONCLUSIONS: TDABC is a feasible methodology to quantify the cost of resources required for delivery of adjuvant IMRT and brachytherapy and produces directionally accurate costing data as compared with reimbursement calculations. Such data can inform institution-specific financial analyses, resource allocation, and operational workflows.

Volumetric assessment of apparent diffusion coefficient predicts outcome following chemoradiation for cervical cancer.

OBJECTIVE: To determine the utility of volumetric diffusion weighted imaging (DWI) compared to other clinical factors for predicting recurrence and survival in cervical cancer patients treated with definitive chemoradiation. METHODS AND MATERIALS: We retrospectively studied cervical cancer patients treated with definitive chemoradiation between 2009-2013 at a single institution with a baseline MRI with DWI and 18F-FDG positron emission tomography/computed tomography (FDG-PET) scan. To identify clinical and imaging metrics correlated with survival and recurrence endpoints, variable importance values were calculated from random forest models. To provide clinically relevant threshold values, recursive partitioning analysis dichotomized patients into potential risk groups based on selected metrics. Cox's proportional hazard models assessed the effect of clinical and imaging factors on survival endpoints. RESULTS: Ninety-three patients were included in the analysis (median age 50 years). At a median follow-up of 35.6 months, 32 patients (34%) had disease recurrence. In the best multivariate model including clinical and imaging parameters, 90th percentile ADC < 1.917 was the only significantly associated factor with worse progression free survival (PFS). Overall survival, PFS, and distant metastasis free survival (DMFS) were significantly different between patient groups divided on 90th percentile ADC with threshold of 1.917 × 10-3 mm2/s and MRI volume with threshold of 18.9 cc (P = 0.037, P = 0.0002, P = 0.001). High MRI volume and low ADC were associated with worse clinical outcomes. CONCLUSIONS: Volumetric 90th percentile ADC value of the primary tumor on pretreatment MRI was a significant predictor of PFS and DMFS in cervical cancer patients, independent of established clinical factors and SUV on FDG-PET.

A risk assessment of automated treatment planning and recommendations for clinical deployment.

PURPOSE: To assess the risk of failure of a recently developed automated treatment planning tool, the radiation planning assistant (RPA), and to determine the reduction in these risks with implementation of a quality assurance (QA) program specifically designed for the RPA. METHODS: We used failure mode and effects analysis (FMEA) to assess the risk of the RPA. The steps involved in the workflow of planning a four-field box treatment of cervical cancer with the RPA were identified. Then, the potential failure modes at each step and their causes were identified and scored according to their likelihood of occurrence, severity, and likelihood of going undetected. Additionally, the impact of the components of the QA program on the detectability of the failure modes was assessed. The QA program was designed to supplement a clinic's standard QA processes and consisted of three components: (a) automatic, independent verification of the results of automated planning; (b) automatic comparison of treatment parameters to expected values; and (c) guided manual checks of the treatment plan. A risk priority number (RPN) was calculated for each potential failure mode with and without use of the QA program. RESULTS: In the RPA automated treatment planning workflow, we identified 68 potential failure modes with 113 causes. The average RPN was 91 without the QA program and 68 with the QA program (maximum RPNs were 504 and 315, respectively). The reduction in RPN was due to an improvement in the likelihood of detecting failures, resulting in lower detectability scores. The top-ranked failure modes included incorrect identification of the marked isocenter, inappropriate beam aperture definition, incorrect entry of the prescription into the RPA plan directive, and lack of a comprehensive plan review by the physician. CONCLUSIONS: Using FMEA, we assessed the risks in the clinical deployment of an automated treatment planning workflow and showed that a specialized QA program for the RPA, which included automatic QA techniques, improved the detectability of failures, reducing this risk. However, some residual risks persisted, which were similar to those found in manual treatment planning, and human error remained a major cause of potential failures. Through the risk analysis process, we identified three key aspects of safe deployment of automated planning: (a) user training on potential failure modes; (b) comprehensive manual plan review by physicians and physicists; and (c) automated QA of the treatment plan.

Society of Gynecologic Oncology Future of Physician Payment Reform Task Force report: The Endometrial Cancer Alternative Payment Model (ECAP).

Health care in the United States is in the midst of a significant transformation from a "fee for service" to a "fee for value" based model. The Medicare Access and CHIP Reauthorization Act of 2015 has only accelerated this transition. Anticipating these reforms, the Society of Gynecologic Oncology developed the Future of Physician Payment Reform Task Force (PPRTF) in 2015 to develop strategies to ensure fair value based reimbursement policies for gynecologic cancer care. The PPRTF elected as a first task to develop an Alternative Payment Model for thesurgical management of low risk endometrial cancer. The history, rationale, and conceptual framework for the development of an Endometrial Cancer Alternative Payment Model are described in this white paper, as well as directions forfuture efforts.

Clinical trials in low and middle-income countries - Successes and challenges.

Gynecologic malignancies affect women in low and middle-income countries (LMICs) at equal or higher rates compared to high income countries (HICs), yet practice guidelines based on clinical trials performed in HICs do not routinely account for resource disparities between these regions. There is a need and growing interest for executing clinical trials in LMICs. This has led to the creation of multinational cooperative groups and the initiation of several ongoing clinical trials in Mexico, China, and Korea. In this article we describe the challenges involved in initiating clinical trials in LMICs, review current efforts within surgical, medical, and radiation oncology, and introduce high priority topics for future research.

Prospective study of symptom assessment among patients with cervical cancer during concurrent chemoradiotherapy with weekly cisplatin or every-3-week cisplatin and 5-fluorouracil.

PURPOSE: In this prospective study, symptoms were assessed in patients with locally advanced cervical cancer undergoing concurrent chemoradiotherapy (CTRT) with either weekly cisplatin (WP) or every-3-week cisplatin/5-fluorouracil (PF). MATERIALS AND METHODS: Patients with 1994 International Federation of Gynecology and Obstetrics stage IIB to IVA disease, biopsy-proven involved pelvic nodes, or gross tumor size greater than 5 cm were eligible. Patients requiring paraaortic radiotherapy were excluded. With the use of a modified Edmonton Symptom Assessment Scale, patients reported symptom severity on an 11-point scale 3 times per week during CTRT and at the first follow-up. The Wilcoxon rank sum test and multilevel mixed-effects linear regression were used to assess the effect of chemotherapy regimen on symptoms. RESULTS: Among the 52 patients included in the final analysis, 37 received WP, 13 received PF, and 2 received 1 cycle of PF followed by WP. Overall compliance with completion of Edmonton Symptom Assessment Scale questionnaires was 75%. There were significant differences in symptom scores for well-being, anorexia, fatigue, diarrhea, and stomatitis favoring the WP regimen. All symptoms except diarrhea were stable and of low intensity in the WP group. In the PF group, symptoms had a cyclical pattern with an initial rise followed by a gradual fall during the 3-week period after chemotherapy. For the 29 patients (56%) who completed the follow-up surveys, scores for all symptoms improved to baseline levels 4 to 6 weeks after treatment. CONCLUSIONS: This analysis provides important patient-reported data regarding the rates and timing of acute symptoms during CTRT that can help clinicians better manage symptoms that impact patients' quality of life.

Advanced cervical cancer treatment in Harris County: pilot evaluation of factors that prevent optimal therapy.

OBJECTIVE: To document obstacles to completing outpatient treatment faced by indigent patients with cervical cancer and compare treatment costs. METHODS: A retrospective pilot case series study assessed all indigent Harris County residents referred from Lyndon Baines Johnson Hospital (LBJ) to The University of Texas M. D. Anderson Cancer Center (M. D. Anderson) for advanced cervical cancer treatment between February 2001 and April 2004. Twenty-seven patients required hospital admission during the expected course of outpatient treatment and were identified as the study group. Nine patients, drawn from the same cohort but able to successfully complete the expected course of treatment as outpatients, were selected as the control group. RESULTS: The median total treatment costs per patient in the study group (n = 27) was 28,892 US dollar more than the median treatment costs for the patients in the control group (n = 9) (P = 0.01). Median number of inpatient days in the study group was 19.6. Social factors identified as significantly different between the study and control groups included transportation difficulties (P = 0.006) and lack of social support (P = 0.08). Additional factors identified in the study group may have social significance such as accessible local housing (11% vs. 0%, P = 0.56) and noncompliance with treatment (37% vs. 11%, P = 0.22). CONCLUSION: A combination of the lack of adequate methods of transportation and social support may contribute to the high cost of treating indigent patients with cervical cancer in Harris County, Texas.

Dosimetric evaluation of the Fletcher-Williamson ovoid for pulsed-dose-rate brachytherapy: a Monte Carlo study.

We used radiochromic film dosimetry to validate a Monte Carlo (MC) model of a 192Ir pulsed-dose-rate (PDR) source inside a Fletcher-Williamson ovoid. MD-55-2 radiochromic film was placed in a high-impact polystyrene phantom in a plane parallel to and displaced 2.0 cm medially from the long axis of the ovoid. MC N-particle transport code (MCNPX) version 2.4 was used to model the ovoid and the 192Ir source. Energy deposition was calculated using a track-length estimator modified by an energy-dependent heating function, which is a good approximation of the collision kerma. To convert the estimates of the MC dose per simulated particle to clinically relevant absolute dosimetry, additional MC models of an actual and a virtual 192Ir source in dry air were simulated to determine air kerma strength for the penetrating part of the photon spectrum (>11.3 keV). The absolute dose distributions predicted by MCNPX agreed with the film results and were within +/-9.4% (k = 2) and within +/-2% or within a distance to agreement of 2 mm for 94% of the dose grid. Additional MC models characterized the uncertainty resulting from source positioning inside the ovoid. For a worst-case scenario of 1 mm off centre from the nominal source position in the 3 mm diameter ovoid shaft, the average dose deviation over the film plane was +/-5% (1sigma = +/-4%), with maximum deviation near the sharp dose-gradient provided by the shields of -20% to + 26%. A validated MC model is the first requirement to simulate common LDR clinical loadings (5-20 mgRaEq) and, thus, will aid in the transition from the current 137Cs Selectron LDR ICBT to PDR for treatment of gynecologic cancers.

A three-dimensional computed tomography-assisted Monte Carlo evaluation of ovoid shielding on the dose to the bladder and rectum in intracavitary radiotherapy for cervical cancer.

PURPOSE: To determine the effects of Fletcher Suit Delclos ovoid shielding on dose to the bladder and rectum during intracavitary radiotherapy for cervical cancer. METHODS AND MATERIALS: The Monte Carlo method was used to calculate the dose in 12 patients receiving low-dose-rate intracavitary radiotherapy with both shielded and unshielded ovoids. Cumulative dose-difference surface histograms were computed for the bladder and rectum. Doses to the 2-cm(3) and 5-cm(3) volumes of highest dose were computed for the bladder and rectum with and without shielding. RESULTS: Shielding affected dose to the 2-cm(3) and 5-cm(3) volumes of highest dose for the rectum (10.1% and 11.1% differences, respectively). Shielding did not have a major impact on the dose to the 2-cm(3) and 5-cm(3) volumes of highest dose for the bladder. The average dose reduction to 5% of the surface area of the bladder was 53 cGy. Reductions as large as 150 cGy were observed to 5% of the surface area of the bladder. The average dose reduction to 5% of the surface area of the rectum was 195 cGy. Reductions as large as 405 cGy were observed to 5% of the surface area of the rectum. CONCLUSIONS: Our data suggest that the ovoid shields can greatly reduce the radiation dose delivered to the rectum. We did not find the same degree of effect on the dose to the bladder. To calculate the dose accurately, however, the ovoid shields must be included in the dose model.