Comparing dosimetry of locally advanced cervical cancer patients treated with 3 versus 4 fractions of MRI-guided brachytherapy.

PURPOSE: To demonstrate the feasibility of treating cervical cancer patients with MRI-guided brachytherapy (MRgBT) using 24 Gy in 3 fractions (F) versus a standard, more resource-intensive regimen of 28 Gy in 4F, and its ability to meet EMBRACE II planning aims. METHODS AND MATERIALS: A retrospective review of 224 patients with FIGO Stage IB-IVA cervical cancer treated with 28 Gy/4F (n = 91) and 24 Gy/3F (n = 133) MRgBT between 2016-2021 was conducted. Multivariable linear regression models were fitted to compare dosimetric parameters between the two groups, adjusting for CTVHR and T stage. RESULTS: Most patients had squamous cell carcinoma, T2b disease, and were treated with intracavitary applicator plus interstitial needles (96%). The 28 Gy/4F group had higher CTVHR (median 28 vs. 26 cm3, p = 0.04), CTVIR D98% (mean 65.5 vs. 64.5 Gy, p = 0.03), rectum D2cm3 (mean 61.7 vs. 59.2 Gy, p = 0.04) and bladder D2cm3 (81.3 vs. 77.9 Gy, p = 0.03). There were no significant differences in the proportion of patients meeting the EMBRACE II OAR dose constraints and planning aims, except fewer patients treated with 28 Gy/4F met rectum D2cm3 < 65 Gy (73 vs. 85%, p = 0.027) and ICRU rectovaginal point < 65 Gy (65 vs. 84%, p = 0.005). CONCLUSIONS: Cervical cancer patients treated with 24 Gy/3F MRgBT had comparable target doses and lower OAR doses compared to those treated with 28 Gy/4F. A less-resource intense fractionation schedule of 24 Gy/3F is an alternative to 28 Gy/4F in cervix MRgBT.

Clinical Evaluation of Deep Learning and Atlas-Based Auto-Contouring of Bladder and Rectum for Prostate Radiation Therapy.

PURPOSE: Auto-contouring may reduce workload, interobserver variation, and time associated with manual contouring of organs at risk. Manual contouring remains the standard due in part to uncertainty around the time and workload savings after accounting for the review and editing of auto-contours. This preliminary study compares a standard manual contouring workflow with 2 auto-contouring workflows (atlas and deep learning) for contouring the bladder and rectum in patients with prostate cancer. METHODS AND MATERIALS: Three contouring workflows were defined based on the initial contour-generation method including manual (MAN), atlas-based auto-contour (ATLAS), and deep-learning auto-contour (DEEP). For each workflow, initial contour generation was retrospectively performed on 15 patients with prostate cancer. Then, radiation oncologists (ROs) edited each contour while blinded to the manner in which the initial contour was generated. Workflows were compared by time (both in initial contour generation and in RO editing), contour similarity, and dosimetric evaluation. RESULTS: Mean durations for initial contour generation were 10.9 min, 1.4 min, and 1.2 min for MAN, DEEP, and ATLAS, respectively. Initial DEEP contours were more geometrically similar to initial MAN contours. Mean durations of the RO editing steps for MAN, DEEP, and ATLAS contours were 4.1 min, 4.7 min, and 10.2 min, respectively. The geometric extent of RO edits was consistently larger for ATLAS contours compared with MAN and DEEP. No differences in clinically relevant dose-volume metrics were observed between workflows. CONCLUSION: Auto-contouring software affords time savings for initial contour generation; however, it is important to also quantify workload changes at the RO editing step. Using deep-learning auto-contouring for bladder and rectum contour generation reduced contouring time without negatively affecting RO editing times, contour geometry, or clinically relevant dose-volume metrics. This work contributes to growing evidence that deep-learning methods are a clinically viable solution for organ-at-risk contouring in radiation therapy.

Long-term patient-reported distress in locally advanced cervical cancer patients treated with definitive chemoradiation.

BACKGROUND AND PURPOSE: To evaluate longitudinal patient-reported distress in cervical cancer patients treated with definitive chemoradiation (CRT). MATERIALS AND METHODS: Between 2011 and 2016, consenting cervical cancer patients treated with definitive CRT who completed ≥ 2 revised Edmonton Symptom Assessment System (ESAS-r) questionnaires at clinical visits, including baseline, were included. A linear mixed model was used to assess the longitudinal trend in ESAS-r. A minimal clinically important difference (MCID) for total ESAS-r score was defined as a change of 3-points for improvement and 4-points for deterioration. The proportion of patients with an MCID over time was described using moving averages. To test for changes, mixed effects logistic models were fitted, each of which included patient-specific random intercepts and random slopes. RESULTS: 67 patients were eligible for analysis (736 ESAS-r assessments). Median (range) follow-up was 24 months (range: 15-45) and compliance at 12 months was 60% (40/67). There was a significant decrease in ESAS-r scores over time. Baseline ESAS-r was strongly predictive of ESAS-r at follow-up (p < 0.001). The proportion of patients with an MCID for improvement from baseline significantly increased over time (p < 0.001) and the proportion with an MCID for deterioration significantly decreased over time (p < 0.001). No predictors for distress were found. CONCLUSIONS: Long-term cervical cancer survivors experience distress that significantly improves over time to an extent expected to be clinically meaningful for patients. Implementing cervical cancer specific patient-reported outcome tools into practice could better inform patient needs.

Clinical Outcomes of Surgically Unresectable Endometrial Cancers.

OBJECTIVE: The objective of this study was to determine the outcomes of patients with unresectable endometrial cancer managed with definitive or neoadjuvant radiation (RT) and/or chemotherapy. MATERIALS AND METHODS: Patients with unresectable stages II to IVA endometrial cancer who were treated with curative intent between January 2000 and March 2018 were identified. Overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method and compared using the log-rank test. Multivariate logistic regression analysis was performed to identify factors associated with receipt of surgery. Multivariate Cox regression analysis was performed to identify factors associated with OS and DFS. RESULTS: Of the 59 patients identified, the median age was 63 years (range: 37 to 88 y) and histology was endometrioid in 59%. Median follow-up was 2.2 years (range: 0.3 to 9.8 y). Seventeen patients (29%) received neoadjuvant chemotherapy, 28 (47%) neoadjuvant radiation, and 14 (24%) definitive RT; 39 (66%) underwent surgery. Patients who received surgery had higher 3-year OS and DFS than those who did not (84% vs. 41%; P<0.001 and 56% vs. 11%; P<0.001, respectively). Factors associated with higher odds of surgical resection included younger age, endometrioid histology, and earlier stage. Younger age, endometrioid histology, and surgical resection were significantly associated with higher OS. Surgical resection was also associated with higher DFS. CONCLUSIONS: Surgical resection following RT and/or chemotherapy for locally advanced, unresectable endometrial cancer is associated with higher DFS and OS and more likely to be achieved in endometrioid subtypes.

Repeatability and reproducibility of MRI-based radiomic features in cervical cancer.

PURPOSE: The aims of this study are to evaluate the stability of radiomic features from T2-weighted MRI of cervical cancer in three ways: (1) repeatability via test-retest; (2) reproducibility between diagnostic MRI and simulation MRI; (3) reproducibility in inter-observer setting. MATERIALS AND METHODS: This retrospective cohort study included FIGO stage IB-IVA cervical cancer patients treated with chemoradiation between 2005 and 2014. There were three cohorts of women corresponding to each aim of the study: (1) 8 women who underwent test-retest MRI; (2) 20 women who underwent MRI on different scanners (diagnostic and simulation MRI); (3) 34 women whose diagnostic MRIs were contoured by three observers. Radiomic features based on first-order statistics, shape features and texture features were extracted from the original, Laplacian of Gaussian (LoG)-filtered and wavelet-filtered images, for a total of 1761 features. Stability of radiomic features was assessed using intraclass correlation coefficient (ICC). RESULTS: The inter-observer cohort had the most reproducible features (95.2% with ICC ≥0.75) whereas the diagnostic-simulation cohort had the fewest (14.1% with ICC ≥0.75). Overall, 229 features had ICC ≥0.75 in all three tests. Shape features emerged as the most stable features in all cohorts. CONCLUSION: The diagnostic-simulation test resulted in the fewest reproducible features. Further research in MRI-based radiomics is required to validate the use of reproducible features in prognostic models.

Patient-reported sexual adjustment after definitive chemoradiation and MR-guided brachytherapy for cervical cancer.

PURPOSE: The treatment of locally advanced cervical cancer with definitive chemoradiation (CRT) is associated with vaginal toxicity and altered sexual satisfaction. This prospective study assessed patient-reported sexual adjustment, vaginal dosimetry, and physician-reported vaginal toxicity in patients with cervical cancer treated with CRT and MR-guided brachytherapy (BT). MATERIALS AND METHODS: Between 2008 and 2010, International Federation of Gynecologists and Obstetricians stage IB-IVA patients with cervical cancer receiving definitive CRT were enrolled in a feasibility study assessing MR-guided BT. Patients completed the validated sexual adjustment questionnaire (SAQ) before BT (baseline) and during followup. Physician-reported vaginal toxicity was recorded. The International Commission on Radiation Units and Measurements rectovaginal point, mean vaginal dose, and D2cm3 were calculated. Mean SAQ scores at baseline and followup assessments were calculated. Mean time effects were estimated using a linear mixed-effects model. A multivariable linear mixed-effects model was used to examine the association between total and individual scores (repeated measures) and covariates. RESULTS: Sixty patients were approached to participate: 29 consented and 27 completed the SAQ at baseline and followup. The diagnosis of cervical cancer and treatment negatively impacted sexual relationships in 61% and 39%, respectively. There were no significant changes in sexual adjustment over time (p = 0.599). There were no associations between sexual adjustment and the International Commission on Radiation Units and Measurements rectovaginal point dose or clinical vaginal involvement. Patients with higher International Federation of Gynecologists and Obstetricians stages (≥IIB) had significantly worse sexual adjustment (p = 0.005). CONCLUSION: CRT and MR-guided BT negatively impacted sexual relationships in patients with cervix cancer; however, there were no significant longitudinal changes in patient-reported sexual adjustment. Worse sexual adjustment may be associated with more advanced disease presentations.

Brachy-ing Unresectable Endometrial Cancers with Magnetic Resonance Guidance.

The standard treatment for endometrial cancer is upfront surgery. However, surgical resection is challenging in locally advanced cases extending to the vagina, bladder, bowel, rectum, or parametria. Historically, these cases were managed palliatively due to the inability to escalate radiation dose safely and accurately, and there is a paucity of literature supporting definitive radiation for these patients. Technological advances in brachytherapy, including magnetic resonance guidance (MR-guidance) and interstitial techniques, have improved target precision and dose escalation without additional toxicity to permit curative management. We report two cases of unresectable, locally advanced endometrial cancers treated with MR-guided radiation.

Deep inspiration breath hold level variability and deformation in locoregional breast irradiation.

PURPOSE: The purpose of this study was to evaluate the dosimetric effect of breath hold level variability and deformation on breast, chest wall, internal mammary chain (IMC) nodes, and heart. METHODS AND MATERIALS: Left-sided post-lumpectomy (n = 12) and postmastectomy (n = 3) patients underwent deep inspiration breath hold (DIBH) and exhale breath hold (EBH) computed tomography (CT) scans. Forward-planned locoregional breast plans were created on the DIBH scan. Two effects were modeled assuming no setup uncertainties: residual motion within the gating window and systematically shallow breath hold levels (BHLs). Real-time position management (RPM) was used to monitor BHL at simulation and during treatment. The RPM data were scaled to simulate BHL variation within symmetric gating window widths of ±1, 3, 5, and 7 mm; the dosimetric impact of this motion was simulated in the treatment planning system. Systematically "shallow" BHL errors were modeled using deformable image registration to map the patient trajectory from DIBH to EBH (n = 12). The deformable vector fields were scaled to produce synthetic CT scans modeling patient position during breath holds 1, 3, 5, and 7 mm shallower than simulator BHL. The original treatment plans were applied to the synthetic CTs and dose was recalculated. RESULTS: Acceptable plan quality was maintained for most patients with motion within gating windows up to ±7 mm. Patients with shallow median BHLs experienced loss of coverage at simulated gating windows ±5 mm or larger. At systematic 3 mm shallow BHL error, 4/12 patients had clinical target volume IMC V80% < 99%; this increased to 11/12 patients at 5 mm. Change in heart dose from systematic BHL errors was negligible. CONCLUSIONS: Motion within gating windows has minimal dosimetric impact for most BHL variability; however, loss of IMC coverage can occur even for small gating windows when BHLs are systematically shallow. This can be mitigated by restricting lower BHL tolerances or accounting for known uncertainties in planning.

Deep inspiration breath-hold produces a clinically meaningful reduction in ipsilateral lung dose during locoregional radiation therapy for some women with right-sided breast cancer.

PURPOSE: The goal of the work described here was to determine whether deep inspiration breath-hold (DIBH) produces a clinically meaningful reduction in pulmonary dose compared with free breathing (FB) during locoregional radiation for right-sided breast cancer. METHODS AND MATERIALS: Four-field, modified-wide tangent plans with full nodal coverage were developed for 30 consecutive patients on paired DIBH and FB CT scans. Nodes were contoured according to European Society for Radiotherapy and Oncology guidelines. Plan metrics were compared using Wilcoxon signed-rank testing. RESULTS: In 21 patients (70%), there was a ≥5% reduction in ipsilateral lung V20Gy with DIBH compared with FB. The mean decrease in ipsilateral lung V20Gy was 7.8% (0%-20%, P < .001). The mean lung dose decreased on average by 3.4 Gy with DIBH (-0.2 to 9.1, P < .001). The mean reduction in liver volume receiving 50% of the prescribed dose was 42.3 cm3 (0-178.9 cm3, P < .001). CONCLUSIONS: DIBH reduced ipsilateral lung V20Gy by ≥5% in the majority of patients. For some patients, the volume of liver receiving a potentially toxic dose decreased with DIBH. DIBH should be available as a treatment strategy to reduce ipsilateral lung V20Gy prior to compromising internal mammary chain nodal coverage for patients with right-sided breast cancer during locoregional radiation therapy if the V20Gy on FB exceeds 30%.

Secondary Breast Cancer Risk by Radiation Volume in Women With Hodgkin Lymphoma.

PURPOSE: To determine whether the risk of secondary breast cancer (SBC) is reduced in women with Hodgkin lymphoma (HL) treated with smaller field radiation therapy (SFRT) versus mantle field radiation therapy (MRT). METHODS AND MATERIALS: We used the BC Cancer Agency (BCCA) Lymphoid Cancer Database to identify female patients treated for HL between January 1961 and December 2009. Radiation therapy volumes were categorized as MRT or SFRT, which included involved field, involved site, or involved nodal radiation therapy. SBC risk estimates were compared using competing risk analysis and Fine and Gray multivariable model: MRT ± chemotherapy, SFRT ± chemotherapy, or chemotherapy-only. RESULTS: Of 734 eligible patients, 75% of the living patients have been followed up for more than 10 years, SBC has developed in 54, and 15 have died of breast cancer. The 20-year estimated risks (competing risk cumulative incidence) for SBC differed significantly: MRT 7.5% (95% confidence interval [CI] 4.4%-11.5%), SFRT 3.1% (95% CI 1.0%-7.7%), and chemotherapy-only 2.2% (95% CI 1.0%-4.8%) (P=.01). Using a Fine and Gray model to control for death and patients lost to follow-up, MRT was associated with a higher risk of SBC (hazard ratio [HR] = 2.9; 95% CI 1.4%-6.0%; P=.004) compared with chemotherapy-only and with SFRT (HR = 3.3; 95% CI 1.3%-8.4%; P=.01). SFRT was not associated with a greater risk of SBC compared with chemotherapy-only (HR = 0.87; 95% CI 0.28%-2.66%; P=.80). CONCLUSION: This study confirms that large-volume MRT is associated with a markedly increased risk of SBC; however, more modern small-volume RT is not associated with a greater risk of SBC than chemotherapy alone.

Comparison of patient-reported outcomes with single versus multiple fraction palliative radiotherapy for bone metastasis in a population-based cohort.

BACKGROUND: Despite randomized control trials showing equivalent efficacy between single-fraction (SF) and multiple-fraction (MF) radiation therapy (RT) for bone metastases (BoM), considerable variation in fractionation exists. We compared patient-reported outcomes (PROs) following SF versus MF RT in a population-based cohort. METHODS: PROs were chosen to assess patients' perception of pain, function, and symptom frustration. Total score was the sum of the 3 questions. RESULTS: 968 patients completed pre and post-RT PROs, 35% (335) had complicated BoM. Overall, there were no differences in total score improvement (79% vs. 83%; p=0.13), nor for complicated BoM (77% vs. 84%; p=0.12), SFRT and MFRT respectively. On multivariate analysis no differences in improvement in total score were observed between SFRT and MFRT overall (OR=0.71; 95% CI 0.49-1.02; p=0.06), nor for complicated BoM (OR=0.74; 95% CI 0.39-1.39; p=0.35). In the complicated BoM subset, pain complete response (CR) (19% vs. 33%; p=0.01) and functional improvement occurred more commonly in the MFRT group (69% vs. 81%; p=0.04). CONCLUSION: Improvements in PROs for pain, function and symptom frustration were similar between SFRT and MFRT supporting the use of hypofractionated regimens. Using a simple, 3-question, telephone-based questionnaire to assess response to palliative RT is a feasible strategy to collect PROs.

Unexpected Symptomatic Pneumonitis Following Breast Tangent Radiation: A Case Report.

Symptomatic radiation pneumonitis (RP) following radiation therapy (RT) to the breast alone is very uncommon. We report a case of an 80-year-old female who presented with fatigue, exertional dyspnea, fever, and cough 11.5 weeks following adjuvant breast RT with tangent fields alone. Imaging was consistent with RP, and she responded to a tapering course of steroids.

Physicians underestimate calcium intake in women.

BACKGROUND AND OBJECTIVES: Personalized nutritional counseling about calcium intake during office encounters requires rapid estimation of calcium intake. We compared the accuracy of physician estimates to a validated calcium intake measure and characterized women whose intakes were incorrectly deemed inadequate by physicians. METHODS: As part of a controlled trial of brief, office-based calcium intake counseling of women, family physicians estimated calcium intake from patients' self-reported intake of dairy food/beverage intake and from their supplement use. We compared estimates to the Short Calcium Questionnaire (SCQ), a validated 7-day dietary recall measure completed by patients. Sensitivity/specificity of physician-estimated calcium intake was estimated by comparison with the SCQ. RESULTS: For 97 women, SCQ rated 32 (33%) as inadequate, 55 (57%) as adequate, and 10 (10%) as excessive. When compared to SCQ, the sensitivity of physician-estimated calcium intake inadequacy was 97% (95% confidence interval [CI]: 94%-100%), specificity was 51% (95% CI: 41%-61%), and positive predictive value was 49% (95% CI: 39%-59%). Women with underestimated intakes were more likely to report a family history of osteoporosis and take a daily multivitamin. The major source of physician underestimation of calcium intake was underestimate of dairy product contribution. CONCLUSIONS: More accurate estimates of dairy-based calcium intake will lead to greater specificity in identifying inadequate calcium intake.

Barriers to supplemental calcium use among women in suburban family practice: a report from the Cleveland Clinic Ambulatory Research Network (CleAR-eN).

BACKGROUND: The majority of adult women in the United States fail to meet daily calcium intake recommendations. This study was undertaken to (1) identify predictors of calcium supplement use versus non-use, (2) understand barriers to calcium supplementation, and (3) determine the potential impact of physician recommendation on calcium supplement use. METHODS: Surveys were self-administered by 185 women, ages 20 to 64, presenting consecutively for care at 6 suburban community-based family medicine practices within the Cleveland Clinic Ambulatory Research Network (CleAR-eN). We compared demographic characteristics, health beliefs, and health behaviors of those women who reported never using calcium supplements with those who presently took calcium supplements. Women who never took calcium were also queried about reasons for non-use and whether physician recommendation would influence their adoption of calcium supplementation. RESULTS: Multivitamin use, self-perceived risk of osteoporosis, and age were independent predictors of calcium supplement use. Leading barriers for never-users were lack of knowledge about the need/importance of increasing calcium intake, lack of motivation to start supplements, and the belief that their dietary calcium intake alone was sufficient. Ninety-six percent of never-users reported that they would consider taking a calcium supplement if recommended by their physician. CONCLUSIONS: Many patient-identified barriers to calcium supplementation seem amenable to focused and brief office-based interventions that could increase the number of women meeting calcium intake guidelines.