Is Substantial Lymphovascular Space Invasion Prognostic in Patients With Pathologically Lymph Node-Negative Endometrial Cancer?

PURPOSE: Lymphovascular space invasion (LVSI) predicts for higher rates of recurrence and increased mortality in endometrial cancer. Using 3-tier LVSI scoring, a PORTEC-1 and -2 trials analysis demonstrated that substantial LVSI was associated with worse locoregional (LR-DFS) and distant metastasis disease-free survival (DM-DFS), and these patients possibly benefited from external beam radiation therapy (EBRT). Furthermore, LVSI is a predictor for lymph node (LN) involvement, but the significance of substantial LVSI is unknown in patients with a pathologically negative LN assessment. We aimed to evaluate clinical outcomes of these patients in relation to the 3-tier LVSI scoring system. METHODS AND MATERIALS: We performed a single-institutional retrospective review of patients with stage I endometrioid-type endometrial cancer who underwent surgical staging with pathologically negative LN evaluation from 2017 to 2019 with 3-tier LVSI scoring (none, focal, or substantial). Clinical outcomes (LR-DFS, DM-DFS, and overall survival) were analyzed using the Kaplan-Meier method. RESULTS: A total of 335 patients with pathologically LN-negative stage I endometrioid-type endometrial carcinoma were identified. Substantial LVSI was present in 17.6% of patients; 39.7% of patients received adjuvant vaginal brachytherapy and 6.9% of patients received EBRT. Adjuvant radiation treatment varied by LVSI status. In patients with focal LVSI, 81.0% received vaginal brachytherapy. Among patients with substantial LVSI, 57.9% received vaginal brachytherapy alone, and 31.6% of patients received EBRT. The 2-year LR-DFS rates were 92.5%, 98.0%, and 91.4% for no LVSI, focal LVSI, and substantial LVSI, respectively. The 2-year DM-DFS rates were 95.5%, 93.3%, and 93.8% for no LVSI, focal LVSI, and substantial LVSI, respectively. CONCLUSIONS: In our institutional study, patients with pathologically LN-negative stage I endometrial cancer with substantial LVSI had similar rates of LR-DFS and DM-DFS compared with patients with none or focal LVSI. These findings highlight the need for multi-institutional studies to validate the prognostic value of substantial LVSI in this patient population.

Dosimetry and Toxicity Outcomes in Patients Treated with Hypofractionated Regional Nodal Irradiation for Breast Cancer: What is the Best Dose-Volume Limit to Minimize Risks of Radiation Pneumonitis?

PURPOSE: Although published data have supported the use of hypofractionated regional nodal irradiation (HF-RNI) for breast cancer, limited dosimetric data exist to evaluate predictors of lung toxicity. The ongoing RT CHARM trial limits the percentage of ipsilateral lung volume that receives ≥18 Gy to 35 to 40%. We assessed dosimetry, toxicity, and disease outcomes in patients with breast cancer treated with HF-RNI with a particular focus on pneumonitis. METHODS AND MATERIALS: We retrospectively reviewed all patients with breast cancer treated with HF-RNI (40-43 Gy in 15-16 fractions) after either lumpectomy or mastectomy at The University of Pittsburgh Medical Center from September 2018 to December 2021 to collect dosimetric and outcomes data. All post-radiation therapy chest computed tomography (CT) scans were manually reviewed for evidence of acute (≤6 months postradiation) or chronic (>6 months postradiation) pneumonitis. RESULTS: One-hundred-ninety-one patients qualified with a median follow-up of 20.3 months (range, 5.1-42.2). Acute grade 1 (G1) pneumonitis was observed in 6.8% of the overall cohort (13 of 191 patients) and 39.4% of the patients (13 of 33) who received a chest CT ≤6 months postradiation therapy. Only 1 patient developed acute G2 pneumonitis. Chronic G1 pneumonitis was observed in 29.8% of the overall cohort (57 of 191 patients) and 77% of patients (57 of 74 patients) who received a chest CT >6 months postradiation therapy. No patients developed acute G3+ or chronic G2+ pneumonitis. CONCLUSIONS: Rates of symptomatic pneumonitis were low in this cohort of patients treated with HF-RNI, even with integration of HER2/neu-directed therapy, chemotherapy, hormone therapy, and internal mammary nodal irradiation. Lung V20Gy <26% appeared safe in this cohort to limit symptomatic pneumonitis, though this is not meant to represent the safe upper limit. Given the low event rate of symptomatic pneumonitis, data from larger cohorts will be needed to assess dosimetric predictors and the safe upper limit of lung dose.

A comparative study using time-driven activity-based costing in single-fraction breast high-dose rate brachytherapy: An integrated brachytherapy suite vs. decentralized workflow.

INTRODUCTION: Precision breast intraoperative radiation therapy (PB-IORT) is a novel approach to adjuvant radiation therapy for early-stage breast cancer performed as part of a phase II clinical trial at two institutions. One institution performs the entire procedure in an integrated brachytherapy suite which contains a CT-on-rails imaging unit and full anesthesia capabilities. At the other, breast conserving surgery and radiation therapy take place in two separate locations. Here, we utilize time-driven activity-based costing (TDABC) to compare these two models for the delivery of PB-IORT. METHODS: Process maps were created to describe each step required to deliver PB-IORT at each institution, including personnel, equipment, and supplies. Time investment was estimated for each step. The capacity cost rate was determined for each resource, and total costs of care were then calculated by multiplying the capacity cost rates by the time estimate for the process step and adding any additional product costs. RESULTS: PB-IORT costs less to deliver at a distributed facility, as is more commonly available, than an integrated brachytherapy suite ($3,262.22 vs. $3,996.01). The largest source of costs in both settings ($2,400) was consumable supplies, including the brachytherapy balloon applicator. The difference in costs for the two facility types was driven by personnel costs ($1,263.41 vs. $764.89). In the integrated facility, increased time required by radiation oncology nursing and the anesthesia attending translated to the greatest increases in cost. Equipment costs were also slightly higher in the integrated suite setting ($332.60 vs. $97.33). CONCLUSIONS: The overall cost of care is higher when utilizing an integrated brachytherapy suite to deliver PB-IORT. This was primarily driven by additional personnel costs from nursing and anesthesia, although the greatest cost of delivery in both settings was the disposable brachytherapy applicator. These differences in cost must be balanced against the potential impact on patient experience with these approaches.

Radiation treatment for refractory endometriosis: a 38-year-old female presenting with vaginal bleeding.

BACKGROUND: Endometriosis is typically managed with a medical or surgical approach, though some patients have medically refractory disease and are poor surgical candidates. CASE PRESENTATION: A 39-year-old woman presented to our facility with uncontrolled bleeding and pain from an endometriotic mass at the vaginal cuff. She had a history of abdominal hysterectomy with bilateral salpingo-oophorectomy, now with medically refractive and inoperable disease due to prior history of vesicovaginal fistula. We prescribed 30 Gy in 10 fractions with 10 MV and 18 MV photons to the target. At follow-up our patient reported a complete resolution of bleeding and pelvic pain. CONCLUSION: Radiation treatment can be an effective treatment for refractory endometriosis.

Intraprostatic calcification and biochemical recurrence in men treated with cesium-131 prostate brachytherapy.

PURPOSE: Baseline intraprostatic calcification (IC) has been shown to be associated with a higher rate of biochemical recurrence (BCR) in men treated with iodine-125 prostate brachytherapy (PB). We evaluated this association in a cohort of men treated with cesium-131 PB. METHODS AND MATERIALS: We retrospectively reviewed the charts of all low- and intermediate-risk prostate cancer patients treated with cesium-131 PB +/- external beam radiotherapy (EBRT) at our institution from 2/2011 to 7/2018. Patients with < 24 months of follow up or those who received androgen deprivation therapy were excluded. Baseline IC status (defined as one or more ICs ≥ 5 mm) was determined on post-PB CT scans. Cox analysis was used to assess predictors of BCR and Kaplan-Meier survival curves were calculated. RESULTS: Two hundred and sixteen low- and intermediate-risk prostate cancer patients treated with cesium-131 PB +/- EBRT were included. Median follow up was 56.9 months (range 24.1-111.4). Overall, 76 (35.2%) patients had baseline IC and 140 (64.8%) did not. Baseline disease characteristics did not differ significantly between groups. On univariate Cox analysis, only risk group (p = 0.047) and initial PSA (p = 0.016) were significant predictors of BCR, whereas baseline IC was not (p = 0.11). The 5-year BCR-free survival in patients with versus without baseline IC was 97.7% versus 93.8% (p = 0.405), respectively. CONCLUSIONS: In a cohort of low- and intermediate-risk prostate cancer patients treated with cesium-131 PB, the rate of BCR in men with baseline IC was low and baseline IC was not associated with a higher risk of BCR.

Hypofractionated Prostate Radiation Therapy: Adoption and Dosimetric Adherence Through Clinical Pathways in an Integrated Oncology Network.

PURPOSE: Updates to consensus guidelines in October 2018 recommending moderately hypofractionated external beam radiotherapy (mHF-EBRT) in prostate cancer lagged several years after publication of evidence supporting its efficacy. In January 2018, we amended our prostate cancer clinical pathway (CP) to facilitate adoption of mHF-EBRT. Herein, we analyze patterns of care and changes in mHF-EBRT use after the CP modification. METHODS: Our prostate CP was amended in January 2018 to make mHF-EBRT the recommended treatment for patients with low- and intermediate-risk prostate cancer pursuing curative EBRT monotherapy. Normal-tissue dose constraints accompanied the CP modification to guide planning. Use of mHF-EBRT from 2015 to 2017 was compared with use in 2018 after the CP modification, using the Cochran-Armitage test for trend. Predictors of mHF-EBRT use and adherence to dose constraints were analyzed with binary logistic regression. RESULTS: In 560 patients treated with EBRT monotherapy, mHF-EBRT use increased from 3.7% in 2015-2017 to 85.6% in 2018 (P < .001), whereas conventionally fractionated EBRT (CF-EBRT) use decreased from 96.3% to 14.4% (P < .001). Consultation year of 2018 (odds ratio [OR], 214.6; 95% CI, 94.5 to 484.6; P < .001), treatment at an academic facility (OR, 4.5; 95% CI, 1.8 to 11.3; P = 0.001), and having a smaller prostate (OR, 0.99; 95% CI, 0.97 to 1.00; P = .028) predicted for mHF-EBRT use. At least five of six recommended bladder and rectal dose constraints were met in 89.4% of patients. CONCLUSION: Modification of our prostate cancer CP, in concert with institutional policies to monitor and audit CP compliance, facilitated rapid adoption of mHF-EBRT in our large, integrated cancer center with good adherence to dosimetric constraints.

Time-driven activity-based costing of a novel form of CT-guided high-dose-rate brachytherapy intraoperative radiation therapy compared with conventional breast intraoperative radiation therapy for early stage breast cancer.

INTRODUCTION: Intraoperative radiation therapy is an emerging option for adjuvant therapy for early stage breast cancer, although it is not currently considered standard of care in the United States. We applied time-driven activity-based costing to compare two alternative methods of breast intraoperative radiation therapy, including treatment similar to the techniques employed in the TARGIT-A clinical trial and a novel version with CT-guidance and high-dose-rate (HRD) brachytherapy. METHODS AND MATERIALS: Process maps were created to describe the steps required to deliver intraoperative radiation therapy for early stage breast cancer at each institution. The components of intraoperative radiation therapy included personnel, equipment, and consumable supplies. The capacity cost rate was determined for each resource. Based on this, the delivery costs were calculated for each regimen. For comparison across centers, we did not account for indirect facilities costs and interinstitutional differences in personnel salaries. RESULTS: The CT-guided, HRD form of intraoperative radiation therapy costs more to deliver ($4,126.21) than the conventional method studied in the TARGIT-A trial ($1,070.45). The cost of the brachytherapy balloon applicator ($2,750) was the primary driver of the estimated differences in costs. Consumable supplies were the largest contributor to the brachytherapy-based approach, whereas personnel costs were the largest contributor to costs of the standard form of intraoperative radiation therapy. CONCLUSIONS: When compared with the more established method of intraoperative radiation therapy using a portable superficial photon unit, the delivery of treatment with CT guidance and HDR brachytherapy is associated with substantially higher costs. The excess costs are driven primarily by the cost of the disposable brachytherapy balloon applicator and, to a lesser extent, additional personnel costs. Future work should include evaluation of a less expensive brachytherapy applicator to increase the anticipated value of brachytherapy-based intraoperative radiation therapy.

Declining brachytherapy utilization for cervical cancer patients - Have we reversed the trend?

OBJECTIVE: Studies examining temporal trends in cervical brachytherapy use are conflicting and examined different health insurance populations. This study examined brachytherapy utilization over time by health insurance type and whether reported declines in brachytherapy have reversed. METHODS: The National Cancer Database (NCDB) was queried for patients with FIGO IIB-IVA cervical cancer treated with definitive chemoradiotherapy between 2004 and 2014, identifying 17,442 patients. Brachytherapy utilization over time and by insurance type and other sociodemographic factors were compared using binary logistic regression. A sensitivity analysis was done in a sub-cohort of patients using the boost modality variable in the NCDB. RESULTS: Brachytherapy utilization declined during 2008-10 (52.6%) compared to 2004-2007 (54.4%; odds ratio [OR] 0.93, 95% confidence interval [CI] 0.86-1.01) and declines were disproportionately larger for patients with government insurance (49.4% vs 52.3%, respectively) than privately-insured patients (57.6% vs 58.9%, respectively). However, rates of brachytherapy use subsequently recovered during 2011-14 in all insurance groups (58.0%, OR 1.24, 95% CI 1.16-1.34) and was especially improved for Medicaid (OR 1.44, 95% CI 1.26-1.65) and uninsured patients (OR 1.28, 95% CI 1.03-1.57). Sensitivity analysis using the boost modality variable confirmed these trends. CONCLUSIONS: In patients with FIGO IIB-IVA cervical cancer treated with definitive chemoradiotherapy from 2004 to 2014, brachytherapy utilization declined during the late 2000s and disproportionately affected patients with government insurance, but subsequently recovered in the early 2010s. Since government insurance covers vulnerable patient populations at-risk for future declines in brachytherapy use, proposed alternative payment models should incentivize cervical brachytherapy to solidify gains in brachytherapy utilization.

Predictors of quality of care and survival in a three-state cohort of locally advanced cervical cancer patients and development of a predictive model to identify women at risk of incomplete treatment.

To expand our prior statewide analysis of care distribution for locally advanced cervical cancer in Virginia to include 2 more states and to develop a tool for predicting quality of care. Complete treatment was defined as receiving chemotherapy (CT), brachytherapy (BT), and external beam radiotherapy.State cancer registry databases yielded a three-state cohort of 3197 women diagnosed with locally advanced cervical cancer from 2000 to 2013. A logistic regression evaluated predictors for receipt of BT, CT, and high (2-3 modalities received) versus low (0-1 modalities received) quality care. A Cox proportional hazards models determined predictors of survival. Finally, a predictive model was developed and preliminarily validated using our cohort.Only 35.3% of the cohort received complete treatment and only 57.3% received BT. Significant predictors of lower odds of receiving high quality care varied by state but included: 66+ age at diagnosis as compared to 18 to 42, 42 to 53, or 53 to 66; cancer stage IVA as compared to IIIx, IIx, or IB2; public insurance with supplement as compared to private; treatment at a low volume facility; and closer distance quintiles to a high volume treatment center as compared to the furthest quintile. Significant predictors of worse survival varied by state but included: low quality score (0-1 modalities received); 2000 to 2004 or 2005 to 2009 year of diagnosis as compared to 2010 to 2013; 66+ age at diagnosis as compared to 18 to 42, 42 to 53, or 53 to 66; cancer stage IVA as compared to IIIx, IIx, or IB2; treatment at a low volume facility; and unmarried/unknown marital status as compared to married. Our treatment quality prediction tool included age, age, treatment at high volume facility, and cancer stage and demonstrated 78.2% sensitivity and a 62.9% specificity.Only 35.3% of patients received complete guidelines-concordant treatment. Additionally, in 2/3 states it appeared that BT usage may have decreased during the study period. Our predictive model may help identify patients/regions at risk of receiving low quality care to target interventions aimed at improving cervical cancer treatment quality and survival.

Radiation-related Lymphopenia after Pelvic Nodal Irradiation for Prostate Cancer.

PURPOSE: Given the uncertainty with regard to the effectiveness of pelvic nodal irradiation (PNI) for prostate cancer, we aimed to determine whether patients with prostate cancer who are treated with PNI are at a higher risk of developing radiation-related lymphopenia (RRL). METHODS AND MATERIALS: The electronic charts of 886 consecutive patients treated with radiation therapy for prostate cancer between 2006 and 2018 at our institution were retrospectively analyzed. Qualifying patients were those with total lymphocyte counts within 1 year before and 3 to 24 months after the start of radiation therapy. Lymphopenia was the primary outcome, and overall survival and biochemical progression-free survival were secondary outcomes. RESULTS: Thirty-six patients with and 95 patients without PNI qualified for inclusion. In the PNI cohort, 61.1% of patients developed RRL (median follow-up total lymphocyte count < 1000 cells/µL) versus 26.3% of non-PNI patients (P < .001). On univariate analysis, initial prostate-specific antigen level, baseline lymphopenia, treatment modality, PNI status, increased planned target volume, and androgen deprivation therapy administration were all significant predictors of RRL (P < .05). On multivariate analysis, PNI status was a significant predictor of RRL (hazard ratio [HR], 3.42; 95% confidence interval [CI], 1.22-9.61; P < .001), as were initial prostate-specific antigen values (HR, 1.05; 95% CI, 1.00-1.11; P = .006) and baseline lymphopenia (HR, 8.32; 95% CI, 2.19-31.6; P = .007). RRL was not predictive for biochemical progression-free survival, distant metastasis, or overall survival on multivariate analysis, but the number of events was likely insufficient for these analyses. CONCLUSIONS: The higher risk of RRL among patients with PNI comports with other papers that show that increased treatment volumes are associated with higher rates of RRL. Mounting evidence for the adverse effects of RRL on clinical outcomes supports the significance of our findings and suggests that further studies are needed on RRL as a potential harm of PNI that may affect the interpretation of results from clinical trials of PNI.