Impact of adjuvant chemotherapy with radiation for node-positive vulvar cancer: A National Cancer Data Base (NCDB) analysis.

BACKGROUND: For node-positive vulvar cancer, adjuvant radiotherapy has an established benefit, whereas the impact of chemotherapy is unknown. A National Cancer Data Base (NCDB) analysis was conducted to determine patterns of care and evaluate the survival impact of adjuvant chemotherapy. METHODS: The NCDB was queried for vulvar cancer patients diagnosed from 1998-2011 who underwent extirpative surgery with confirmed inguinal nodal involvement treated with adjuvant radiotherapy. Patients with inadequate follow-up or non-squamous histologies were excluded. Chi-square test, logistic regression analysis, log-rank test and multivariable Cox proportional regression modeling with adjustment using propensity score with inverse probability of treatment weights (IPTW) were conducted to establish factors associated with utilization and survival. RESULTS: A total of 1797 patients were identified: 26.3% received adjuvant chemotherapy and 76.6% had 1-3 involved lymph nodes. Adoption of adjuvant chemotherapy significantly increased over time, from 10.8% in 1998 to 41.0% in 2006 (p<0.001). Lower utilization was seen in older patients, Northeast or Southern facilities, and patients with more extensive nodal dissection, whereas greater number of involved nodes, stage IVA disease and positive surgical margins led to a higher probability of receiving chemotherapy. Unadjusted median survival without and with adjuvant chemotherapy was 29.7months and 44.0months (p=0.001). On IPTW-adjusted Cox proportional regression modeling, delivery of adjuvant chemotherapy resulted in a 38% reduction in the risk of death (HR 0.62, 95% CI 0.48-0.79, p<0.001). CONCLUSION: In a large population-based analysis, adjuvant chemotherapy resulted in a significant reduction in mortality risk for node-positive vulvar cancer patients who received adjuvant radiotherapy.

Adoption and impact of concurrent chemoradiation therapy for vaginal cancer: a National Cancer Data Base (NCDB) study.

BACKGROUND: Vaginal cancer is an uncommon entity for which concurrent chemoradiation (CCRT) may be used based on small retrospective series and extrapolation from cervical cancer. We explored the adoption rate of CCRT and determined its impact on survival. METHODS: Patients entered into the National Cancer Data Base (NCDB) diagnosed with vaginal cancer from 1998 to 2011 who received definitive radiation therapy were included. Univariate/multivariable exploratory analyses of factors associated with CCRT were performed. Log-rank test and Cox proportional hazards modeling identified the contribution of CCRT on survival. RESULTS: Of the 13,689 patients identified, 8222 (60.1%) received radiation therapy. Of these, 3932 (47.8%) received CCRT and its use increased from 20.8% to 59.1% (1998-2011). Of the 23 patient, disease, facility, and treatment factors, 13 were significantly associated with patient outcomes and were entered into a binary logistic regression model. This evaluation revealed that younger age, larger tumor size, later year of diagnosis, higher facility volume, squamous histology, and higher stage (in order of increasing association) are independently associated with CCRT use. Median overall survival is longer with CCRT compared to radiation alone (56.2 vs. 41.2 months, p<0.0005). On multivariable analysis, younger age, higher facility volume, squamous histology, lower comorbidity score, CCRT, brachytherapy utilization and lower stage (in order of increasing association) are independently prognostic of improved survival. CONCLUSIONS: Use of CCRT for patients with vaginal cancer has increased and is associated with a significant improvement in survival in this large, national cohort. CCRT should be integrated into treatment guidelines for vaginal cancer.

Role of PET/CT imaging in stereotactic body radiotherapy.

Stereotactic body radiotherapy (SBRT) is a relatively new technique that enables delivery of high doses of radiation to malignancies throughout the body with a higher degree of precision than conventional radiation modalities. PET and computed tomography are rapidly being adopted for the evaluation of patients with cancer, and its role in conjunction with SBRT is under active investigation. This article reviews the literature regarding the utility of PET and computed tomography in treatment planning, follow-up imaging, relationship with clinical outcomes, and other topics in patients treated with SBRT. These questions are investigated for cancers of the lung, head and neck, pancreas and liver. A brief overview of various commercially available SBRT treatment systems is also included.

Patterns of care and outcomes for adjuvant treatment of pT3N0 rectal cancer using the National Cancer Database.

BACKGROUND: The standard of care in locally advanced rectal cancer is preoperative chemoradiation followed by surgical resection. However, the optimal treatment paradigm is currently controversial for patients with pathological T3N0 (pT3N0) in the era of total mesorectal excision (TME). Given the paucity of data, we conducted an analysis using the National Cancer Database (NCDB) to identify patterns of care and outcomes. METHODS: We utilized the NCDB to identify 7,836 non-metastatic, pT3N0 rectal cancer patients who did not receive neoadjuvant therapy from 2004-2014. Univariate and multivariable analysis for factors affecting treatment selection were completed using logistic regression. Overall survival (OS) analyses were completed using Cox regression modeling, incorporating propensity scores with inverse probability of treatment weighting (IPTW) and conditional landmark analysis. RESULTS: There was a significant improvement in OS in patients receiving adjuvant chemotherapy (P<0.01) or radiotherapy (RT) with chemotherapy (P<0.01) vs. observation alone. There was no significant difference between RT vs. observation (P=0.54) and chemotherapy vs. chemotherapy with RT cohorts (P=0.15). Multivariable analysis showed age, gender, race, insurance status, income, Charlson-Deyo Comorbidity Condition (CDCC) score, facility location, grade, surgical margin, RT, and chemotherapy to be statistically significant predictors of OS. After correcting for indication and immortal time biases, chemotherapy, with or without RT, improved OS compared with observation [hazard ratio (HR) 0.48, P<0.001]. This benefit was maintained in the margin negative cohort. CONCLUSIONS: Practice patterns vary in the management of pT3N0 rectal cancer patients. This analysis suggests that the use of adjuvant therapy, particularly adjuvant chemotherapy with or without RT, appears to improve OS.

External validation of life expectancy prognostic models in patients evaluated for palliative radiotherapy at the end-of-life.

BACKGROUND: The TEACHH and Chow models were developed to predict life expectancy (LE) in patients evaluated for palliative radiotherapy (PRT). We sought to validate the TEACHH and Chow models in patients who died within 90 days of PRT consultation. METHODS: A retrospective review was conducted on patients evaluated for PRT from 2017 to 2019 who died within 90 days of consultation. Data were collected for the TEACHH and Chow models; one point was assigned for each adverse factor. TEACHH model included: primary site of disease, ECOG performance status, age, prior palliative chemotherapy courses, hospitalization within the last 3 months, and presence of hepatic metastases; patients with 0-1, 2-4, and 5-6 adverse factors were categorized into groups (A, B, and C). The Chow model included non-breast primary, site of metastases other than bone only, and KPS; patients with 0-1, 2, or 3 adverse factors were categorized into groups (I, II, and III). RESULTS: A total of 505 patients with a median overall survival of 2.1 months (IQR: 0.7-2.6) were identified. Based on the TEACHH model, 10 (2.0%), 387 (76.6%), and 108 (21.4%) patients were predicted to live >1 year, >3 months to ≤1 year, and ≤3 months, respectively. Utilizing the Chow model, 108 (21.4%), 250 (49.5%), and 147 (29.1%) patients were expected to live 15.0, 6.5, and 2.3 months, respectively. CONCLUSION: Neither the TEACHH nor Chow model correctly predict prognosis in a patient population with a survival <3 months. A better predictive tool is required to identify patients with short LE.

Physician-Predicted Prognosis and Palliative Radiotherapy Treatment Utilization at the End of Life: An Audit of a Large Cancer Center Network.

CONTEXT: At our institution, clinical pathways capture physicians' prognostication of patients being evaluated for palliative radiotherapy. We hypothesize a low utilization rate of long-course radiotherapy (LCRT) and stereotactic ablative radiotherapy (SAbR) among patients seen at the end of life, especially those with physician-predicted poor prognosis. OBJECTIVE: To analyze utilization rates and predictors of LCRT and SAbR at the end of life. METHODS: A retrospective review was conducted on patients who were evaluated for palliative radiotherapy between January 2017 and August 2019 and died within 90 days of consultation. Binary logistic regression was used to identify predictors for utilization of LCRT (≥10 fractions) and SAbR. RESULTS: A total of 1608 patients were identified, of which 1038 patients (64.6%) were predicted to die within a year. Six hundred ninety-three patients (66.8%) out of 1038 were prescribed LCRT or SAbR. On a multivariate analysis, patients were less likely to be prescribed LCRT if treated at an academic site (odds ratio [OR], 0.30; 95% confidence interval [CI], 0.23-0.39; P < 0.01) and treated for bone metastases (OR, 0.08; 95% CI, 0.05-0.11; P < 0.01) or other nonbrain/nonbone metastases (OR, 0.19; 95% CI, 0.13-0.30; P < 0.01). SAbR was less likely to be prescribed among patients predicted to die within a year (OR, 0.09; 95% CI, 0.06-0.16; P < 0.01), treated for bone metastases (OR, 0.13; 95% CI, 0.07-0.22; P < 0.01), with poor performance status (OR, 0.51; 95% CI, 0.31-0.85; P = 0.01), and with a breast primary (OR, 0.35; 95% CI, 0.15-0.82; P = 0.02). CONCLUSION: Although most patients were predicted to have a limited prognosis, LCRT and SAbR were commonly prescribed at the end of life.

The mitochondria-targeted nitroxide JP4-039 augments potentially lethal irradiation damage repair.

It was unknown if a mitochondria-targeted nitroxide (JP4-039) could augment potentially lethal damage repair (PLDR) of cells in quiescence. We evaluated 32D cl 3 murine hematopoietic progenitor cells which were irradiated and then either centrifuged to pellets (to simulate PLDR conditions) or left in exponential growth for 0, 24, 48 or 72 h. Pelleted cells demonstrated cell cycle arrest with a greater percentage in the G(1)-phase than did exponentially growing cells. Irradiation survival curves demonstrated a significant radiation damage mitigation effect of JP4-039 over untreated cells in cells pelleted for 24 h. No significant radiation mitigation was detected if drugs were added 48 or 72 h after irradiation. Electron paramagnetic resonance spectroscopy demonstrated a greater concentration of JP4-039 in mitochondria of 24 h-pelleted cells than in exponentially growing cells. These results establish a potential role of mitochondria-targeted nitroxide drugs as mitigators of radiation damage to quiescent cells including stem cells.

Extended field intensity modulated radiation therapy for gynecologic cancers: Is the risk of duodenal toxicity high?

PURPOSE: There have been conflicting reports regarding the incidence of duodenal toxicity in patients receiving intensity modulated radiation therapy (IMRT) with an extended field covering the para-aortic (PA) lymph nodes for gynecologic cancers. We reviewed our experiences and rates of duodenal toxicity in patients treated with extended field IMRT. METHODS AND MATERIALS: Patients with either cervical or endometrial cancer who were treated with IMRT to the PA nodes for involved lymph nodes or for prophylactic intent between 2005 and 2013 were included. For prophylactic intent, the radiation dose to the PA nodes was 45 Gy in 25 fractions. For involved lymph nodes, a boost was delivered to the gross disease with a 0.7-cm expansion, with editing for critical structures. The entire duodenum was retrospectively contoured on all patients from the gastric outlet to the jejunal transition. RESULTS: We identified 76 eligible patients with endometrial and cervical cancer. The PA region was treated prophylactically in 46.1% (n = 35) and for involved PA lymph nodes in 53.9% (n = 41). The duodenum was contoured on all patients with a median volume of 83.2 cm(3) (range, 21.2-174.9 cm(3)). The mean volume of duodenum receiving 55 Gy (V55) for those treated prophylactically and for involved PA nodes was 0 cm(3) and 0.8 cm(3) (range, 0-10.6 cm(3)), respectively (P = .014). Specifically, no patient had a V55 >15 cm(3). The mean V40 was 28.3 cm(3) (range, 0-77.3 cm(3)) and 41.4 (range, 0-90.0 cm(3)), respectively (P = .016). The mean dose delivered to 2 cm(3) of the duodenum was 34.9 Gy (range, 0-52.3 Gy) and 50.1 Gy (range, 31.3 - 58.3 Gy), respectively. Grade 3 acute gastrointestinal toxicity was recorded in 3.9% (n = 3) of patients. CONCLUSIONS: In our experience, the treatment of PA lymph nodes using an IMRT technique is associated with a low duodenal toxicity profile and there has been no high-grade late duodenal toxicity.

Changing practice patterns for breast cancer radiation therapy with clinical pathways: An analysis of hypofractionation in a large, integrated cancer center network.

PURPOSE: Hypofractionated whole breast irradiation (HF-WBI) following breast conserving surgery has produced excellent outcomes, but utilization remains limited. We evaluated the impact of a clinical pathway in the adoption of HF-WBI in a large, integrated radiation oncology network. METHODS AND MATERIALS: We identified patients aged ≥70 years treated for breast cancer or ductal carcinoma in situ. Patients treated with palliative intent, accelerated partial breast radiation, following mastectomy, or with axillary nodal, supraclavicular, or internal mammary fields were excluded. HF-WBI was defined as ≤20 fractions with a dose/fraction ≥2.5 Gy. Multivariate analysis identified variables associated with increased HF-WBI utilization. RESULTS: We identified 2426 patients meeting inclusion criteria. HF-WBI utilization increased significantly from 6.5% (22.0% academic, 2.0% community) before pathway modification to 33.8% afterwards (68.5% academic, 25.3% community, P<.001). For academic physicians, the relative risk of HF-WBI utilization was 3.8 following publication of the seminal HF-WBI trial and 10.6 following pathway modification (P < .001). For community physicians, the relative risk of HF-WBI utilization did not significantly change following publication but was 21.0 following pathway modification (P < .001). The increased adoption of HF-WBI saved an estimated $154,000 annually in our network. CONCLUSIONS: We found that our implementation of clinical pathways substantially increased adoption of HF-WBI for breast cancer. We found no significant change in utilization of HF-WBI among community physicians following publication of a seminal trial for HF-WBI until after clinical pathway implementation, which increased the use of HF-WBI by 20-fold. Clinical pathways may be effective in changing practice patterns, disseminating evidence, and realizing health care savings.

Clinical Pathways: A Catalyst for the Adoption of Hypofractionation for Early-Stage Breast Cancer.

PURPOSE: Hypofractionated whole-breast irradiation (HF-WBI) remains underutilized in the United States despite support by multiple clinical trials. We evaluated the success of iterative modifications of our breast cancer clinical pathway on the adoption of HF-WBI in a large, integrated radiation oncology network. METHODS AND MATERIALS: The breast clinical pathway was modified in January 2011 (Amendment 1) to recommend HF-WBI as the first option for women ≥70 of age with stages 0 to IIA, while maintaining conventional fractionation (CF) as a pathway-concordant secondary option. In January 2013 (Amendment 2), the pathway's HF-WBI recommendation was extended to women ≥50 years of age. In January 2014 (Amendment 3), the pathway mandated HF-WBI as the only pathway-concordant option in women ≥50 years of age, and all pathway-discordant plans were subject to peer review and justification. Women ≥50 years of age with ductal carcinoma in situ or invasive breast cancer who underwent breast conserving surgery and adjuvant WBI were included in this analysis. RESULTS: We identified 5112 patients from 2009 to 2014 who met inclusion criteria. From 2009 to 2012, the overall HF-WBI use rate was 8.3%. Following Amendments 2 and 3 (2013 and 2014, respectively), HF-WBI use significantly increased to 21.8% (17.3% in the community, 39.7% at academic sites) and 76.7% (75.5% in the community, 81.4% at academic sites), respectively (P<.001). Compared to 2009 to 2012, the relative risk of using HF-WBI was 7.9 (95% confidence interval: 7.1-8.6, P<.001) and 10.7 (95% CI: 10.3-11.0, P<.001), respectively, after Amendments 2 and 3, respectively. Age ≥70 and treatment at an academic site increased the likelihood of receiving HF-WBI in 2009 to 2012 and following Amendment 2 (P<.001). CONCLUSIONS: This study demonstrates the transformative effect of a clinical pathway on patterns of care for breast radiation therapy. Although our initial HF-WBI use rate was low (8%-22%) and consistent with national rates, the clinical pathway approach dramatically increased adoption rate to >75%. In contrast to passive guidelines, clinical pathways serve as active tools to promote current best practices.

Cost-effectiveness analysis of 3D image-guided brachytherapy compared with 2D brachytherapy in the treatment of locally advanced cervical cancer.

PURPOSE: Three-dimensional image-guided brachytherapy (IGBT) is a significant advance in locally advanced cervical cancer treatment. However, its cost-effectiveness (C/E) is unknown. We performed a C/E analysis of IGBT compared with conventional (two-dimensional [2D]) brachytherapy in the treatment of locally advanced cervical cancer. METHODS AND MATERIALS: A Markov model was constructed to model locally advanced cervical cancer treated with five fractions of high-dose-rate brachytherapy. The model captured clinical parameters, quality of life utility, and treatment costs through the literature review. Costs were 2013 Medicare reimbursement. Strategies were compared using the incremental cost-effectiveness ratio (ICER), and effectiveness was measured in quality-adjusted life-years (QALYs). To account for uncertainty, one-way, two-way, and probabilistic sensitivity analyses were performed. Strategies were evaluated from a payer's perspective with a willingness-to-pay threshold of $50,000/QALY gained. RESULTS: Treatment costs for five fractions of IGBT and 2D brachytherapy were $21,374 and $17,931, respectively. In the base-case analysis, the IGBT strategy costs $3003 more than 2D brachytherapy while gaining 0.16 QALYs, resulting in an ICER of $18,634 per QALY gained. In one-way sensitivity analyses, results were most sensitive to variation of treatment costs, but the ICER remained <$50,000/QALY gained for all cost ranges. Variation of survival, local control, and complication rates was less influential. A probabilistic sensitivity analysis demonstrated that IGBT was favored in 63% of model iterations at a $50,000/QALY gained threshold. CONCLUSION: IGBT for locally advanced cervical cancer is a C/E option compared with 2D brachytherapy. These findings were robust to variation of parameter values supporting the routine use of IGBT in locally advanced cervical cancer.

Quantitative evaluation of radiation oncologists' adaptability to lower reimbursing treatment programs.

PURPOSE: Rapid development of sophisticated modalities has challenged radiation oncologists to evaluate workflow and care delivery processes. Our study assesses treatment modality use and willingness to alter management with anticipated limitations in reimbursement and resources. METHODS AND MATERIALS: A web-based survey was sent to 43 radiation oncologists in a National Cancer Institute-designated comprehensive cancer center network. The survey contained 7 clinical cases with various acceptable treatment options based on our institutional clinical pathways. Each case was presented in 3 modules with varying situations: (1) unlimited resources with current reimbursement, (2) restricted reimbursement (bundled payment), and (3) both restricted reimbursement and resources. Reimbursement rates were based on the 2013 Medicare fee schedule. Adoption of lower reimbursing options (LROs) was defined as the percentage of scenarios in which a respondent selected an LRO compared with baseline. RESULTS: Forty-three physicians completed the survey, 11 (26%) at academic and 32 (74%) at community facilities. When bundled payment was imposed (module 1 vs 2), an increase in willingness to adopt LROs was observed (median 11.1%). When physicians were limited to both bundled payment and resource restriction, adoption of LROs was more pronounced (module 1 vs 3; median 22.2%, P < .01). There was a trend to selecting LROs between module 1 and 2 that reached significance when transitioning from module 1 to 3. A positive correlation between years in clinical practice and adoption of LROs was demonstrated (r(2) = 0.181, P<.01). This association remained significant when stratifying respondents by experience (≤25 vs >25 years, P = .02). CONCLUSIONS: Radiation oncologists were more likely to choose lower reimbursing treatment options when both resource restriction and bundled payment were presented. Those with fewer years of clinical practice were less inclined to alter management, perhaps reflecting modern residency training. Future cost-utility analyses may help to better guide radiation oncologists in selection of LROs.

Cost-effectiveness analysis of single fraction of stereotactic body radiation therapy compared with single fraction of external beam radiation therapy for palliation of vertebral bone metastases.

PURPOSE: Stereotactic body radiation therapy (SBRT) has been proposed for the palliation of painful vertebral bone metastases because higher radiation doses may result in superior and more durable pain control. A phase III clinical trial (Radiation Therapy Oncology Group 0631) comparing single fraction SBRT with single fraction external beam radiation therapy (EBRT) in palliative treatment of painful vertebral bone metastases is now ongoing. We performed a cost-effectiveness analysis to compare these strategies. METHODS AND MATERIALS: A Markov model, using a 1-month cycle over a lifetime horizon, was developed to compare the cost-effectiveness of SBRT (16 or 18 Gy in 1 fraction) with that of 8 Gy in 1 fraction of EBRT. Transition probabilities, quality of life utilities, and costs associated with SBRT and EBRT were captured in the model. Costs were based on Medicare reimbursement in 2014. Strategies were compared using the incremental cost-effectiveness ratio (ICER), and effectiveness was measured in quality-adjusted life years (QALYs). To account for uncertainty, 1-way, 2-way and probabilistic sensitivity analyses were performed. Strategies were evaluated with a willingness-to-pay (WTP) threshold of $100,000 per QALY gained. RESULTS: Base case pain relief after the treatment was assumed as 20% higher in SBRT. Base case treatment costs for SBRT and EBRT were $9000 and $1087, respectively. In the base case analysis, SBRT resulted in an ICER of $124,552 per QALY gained. In 1-way sensitivity analyses, results were most sensitive to variation of the utility of unrelieved pain; the utility of relieved pain after initial treatment and median survival were also sensitive to variation. If median survival is ≥11 months, SBRT cost <$100,000 per QALY gained. CONCLUSION: SBRT for palliation of vertebral bone metastases is not cost-effective compared with EBRT at a $100,000 per QALY gained WTP threshold. However, if median survival is ≥11 months, SBRT costs ≤$100,000 per QALY gained, suggesting that selective SBRT use in patients with longer expected survival may be the most cost-effective approach.

Impact of dynamic changes to a bone metastases pathway in a large, integrated, National Cancer Institute-designated comprehensive cancer center network.

PURPOSE: Studies suggest equivalent pain relief from bone metastases after radiation therapy with >10-fraction regimens and shorter courses. Although American Society for Radiation Oncology evidence-based guidelines and the Choosing Wisely campaign endorse single-fraction treatments and caution against the use of extended courses, publications report single-fraction utilization rates below 5%. We evaluated the impact of our bone metastasis clinical pathway on the adoption of short-course palliative radiation in a large, integrated radiation oncology network. METHODS AND MATERIALS: We implemented a clinical pathway for the management of bone metastases in 2003 that required the entry of management decisions into an online tool that subjected off-pathway choices to peer review beginning in 2009. In 2014, the pathway was modified to encourage single-fraction treatments, and the use of >10 fractions was considered off pathway. Data were obtained from 16 integrated sites (4 academic, 12 community) from 2003 through 2014. Multivariate logistic regression was conducted to establish factors associated with treatment with a single fraction and with >10 fractions. RESULTS: In this study, 12,678 unique courses were delivered. From 2003 to 2008, the single-fraction utilization rate was 7.6%. This increased to 10.9% from 2009 to 2013 and to 15.8% in 2014. The odds ratios for single-fraction use were 1.59 (95% confidence interval [CI], 1.39-1.81) and 2.58 (95% CI, 2.11-3.15) for 2009-2013 and 2014, respectively. Academic physicians were more likely to treat with a single fraction (odds ratio, 5.00; 95% CI, 4.38-5.71). Use of >10-fraction regimens significantly decreased from 18.6% in 2003-2008 to 15.2% in 2009-2013 and 9.7% in 2014. CONCLUSIONS: Although our single-fraction utilization rate was initially in line with national rates (7.6%), the adoption rate increased to >15%. The use of >10-fraction regimens decreased significantly, predominantly among community practices. By 2014, >90% of courses were delivered with <10 fractions. This study demonstrates that provider-driven clinical pathways are able to standardize practice patterns and promote change consistent with evidence-based guidelines.

Patterns of care and brachytherapy boost utilization for vaginal cancer in the United States.

PURPOSE: Vaginal cancer is an uncommon malignancy that is usually treated with definitive radiation therapy. Following external beam radiation therapy (EBRT), a brachytherapy boost is delivered to achieve a total dose of 70-85 Gy. We sought to determine the trends of brachytherapy boost utilization in the treatment of vaginal cancer and to identify the factors associated with its utilization. METHODS AND MATERIALS: Using the National Cancer Data Base (NCDB), we identified 1530 patients with vaginal cancer from 2004 to 2011 who were treated with radiation therapy and had a recorded boost modality. The following additional variables were identified: age, year of diagnosis, Charlson/Deyo comorbidity score, stage, histology, race, brachytherapy dose rate, brachytherapy applicator technique, treatment facility volume, and utilization of chemotherapy. Multivariable logistic regression analysis was performed to identify factors independently associated with brachytherapy boost. RESULTS: Seventy-seven percent of the 1530 women received brachytherapy boost and 23% received EBRT boost. The rate of brachytherapy boost utilization decreased from 87.7% in 2004 to 68.6% in 2011 (P < .001). Of all the nonbrachytherapy boost modalities, intensity modulated radiation therapy (IMRT) demonstrated the greatest increase (4.5% to 23.5%). For those who had brachytherapy boost, the rate of high-dose-rate increased from 76.3% to 90.8% (P = .02). Multivariate analysis revealed that high facility volume was associated with increased odds of brachytherapy boost (odds ratio [OR], 2.3; range, 1.5-3.4). Higher stage and advanced age were associated with decreased odds of brachytherapy boost (OR, 0.2; range, 0.1-0.3 and OR, 0.5; range, 0.3-0.8). Utilization of chemotherapy, histology, race, and comorbidity index were not significantly associated with brachytherapy boost utilization. CONCLUSIONS: Using the NCDB, we identified a concerning decline in the utilization of brachytherapy boost for those with vaginal cancer and a corresponding increase in IMRT boost technique. The strongest factor predicting for brachytherapy boost utilization is treatment at a high volume facility.

Patterns of care for omission of radiation therapy for elderly women with early-stage breast cancer receiving hormonal therapy.

PURPOSE: For well-selected elderly women who undergo segmental mastectomy for early-stage, estrogen receptor-positive breast cancer, hormonal therapy alone is emerging as an acceptable adjuvant therapy option since the initial publication of Cancer and Leukemia Group B 9343 study in 2004 and update in 2013. The rate of adoption of adjuvant hormonal therapy alone in lieu of radiation therapy (RT) and its associated patterns of care is not known in the United States and was the subject of this study. METHODS AND MATERIALS: We used the National Cancer Data Base to identify women aged ≥70 diagnosed with T1N0/T1Nx invasive breast cancer who underwent segmental mastectomy between 1998 and 2011. Because hormone receptor status was not specifically and reliably coded, only those who received hormonal therapy were included in this analysis. Univariate and multivariable exploratory analyses of factors associated with the use of RT were performed using SPSS, version 17.0. RESULTS: Of the 182,115 patients who met inclusion criteria, 97,530 (53.6%) patients underwent hormonal therapy and were included in the analysis. The RT utilization rate in this subset decreased with time from 84.9% in 1998 to 75.1% in 2011 (P< .001). Multivariable analysis revealed that the factors associated with decreased use of RT include (in order of association): older age, later year of diagnosis, greater comorbidity score, low grade, lack of insurance, treatment at academic facility, race, rural location, lower median income, and distance from facility. CONCLUSIONS: This study assesses the patterns of care associated with the omission of RT in elderly women with early-stage breast cancer who received adjuvant hormonal therapy. Since the publication of major clinical trials, this strategy has been increasingly adopted. The strongest predictors of using this strategy included advanced patient age, high comorbidity score, and low-grade disease.

Dosimetric comparison of multichannel with one single-channel vaginal cylinder for vaginal cancer treatments with high-dose-rate brachytherapy.

PURPOSE: To compare the three-dimensional (3D) image (CT/MR)-based planning with a multichannel vaginal cylinder (MVC) to a single-channel vaginal cylinder (SVC) for the treatment of vaginal cancer. METHODS AND MATERIALS: A total of 20 consecutive patients were treated with 3D CT/MR image-based high-dose-rate (HDR) brachytherapy using an MVC. All patients received external beam radiation therapy before HDR brachytherapy. A brachytherapy dose of 20-25Gy of more than five fractions was delivered to clinical target volume (CTV). Retrospectively, treatment plans for all patients were generated using the central channel only to mimic an SVC applicator. The SVC plans were optimized to match CTV coverage with MVC plans. Dose homogeneity index as well as bladder, rectum, sigmoid, and urethral doses were compared. RESULTS: The mean D90 for CTV was 74.2Gy (range: 48.8-84.1Gy). The mean (±standard deviation) of dose homogeneity index for MVC vs. SVC was 0.49 (±0.19) and 0.52 (±0.23), respectively (p=0.09). Mean bladder 0.1, 1, and 2cc doses for MVC vs. SVC were 69 vs. 71.2Gy (p=0.35), 61.4 vs. 63.8Gy (p=0.1), and 59.5 vs. 60.9Gy (p=0.31), respectively. Similarly, mean rectum 0.1, 1, and 2cc doses for MVC vs. SVC were 67.2 vs. 75.4Gy (p=0.005), 60.0 vs. 65.6Gy (p=0.008), and 57.3 vs. 62.0Gy (p=0.015), respectively, and mean sigmoid doses were 56.3 vs. 60.5Gy (p=0.10), 50.9 vs. 53.1Gy (p=0.09), and 49.1 vs. 50.7Gy (p=0.10), respectively. CONCLUSION: The 3D CT-/MR-based plan with MVC may provide better dose distribution in the management of certain clinical situations of vaginal cancer requiring intracavitary brachytherapy, especially in minimizing potential late rectal complications.

Urethral dosimetry and toxicity with high-dose-rate interstitial brachytherapy for vaginal cancer.

PURPOSE: The tolerance and complication rates of the urethra are unknown for the interstitial high-dose-rate brachytherapy (HDR-BT) for vaginal cancer. METHODS AND MATERIALS: Patients with vaginal cancer near/involving the urethra who were treated with HDR-BT between 2008 and 2011 were included. Patients received mean external beam dose of 48.0Gy followed by mean HDR-BT dose of 4.5Gy/fraction for five fractions. With CT-based planning, the urethra was contoured from the bladder neck to the meatus. Doses were converted to the biologically equivalent dose in 2Gy/fraction (EQD2). RESULTS: A total of 16 patients were included, and the EQD2D90 was 74.9Gy. The urethral volume was 1.31cm(3), and the EQD2 to 0.1 and 1cm(3) were 76.2 and 48.9Gy, respectively. Two of the 6 patients with urethral involvement developed urethral necrosis. The D90 for these 2 patients was 76.8Gy, and the urethral doses to 0.1 and 1cm(3) were 95.1 and 45.8, respectively. Those who developed severe urethral toxicity had a trend to urethral EQD2 (95.1Gy vs. 73.4Gy, p=0.1) and significantly higher dose per fraction of HDR-BT to 0.1cm(3) of the urethra (5.7Gy vs. 3.7Gy, p=0.02) when compared with those who did not develop severe urethral toxicity. CONCLUSIONS: This study is among the first to assess urethral dosimetry for patients treated with HDR-BT for vaginal cancer. Patients who received five fractions of higher than 5Gy/fraction to 0.1cm(3) of urethra (estimated EQD2 of 85Gy) are at increased risk of severe urethral toxicity.

Pathologic response with neoadjuvant chemotherapy and stereotactic body radiotherapy for borderline resectable and locally-advanced pancreatic cancer.

BACKGROUND: Neoadjuvant stereotactic body radiotherapy (SBRT) has potential applicability in the management of borderline resectable and locally-advanced pancreatic adenocarcinoma. In this series, we report the pathologic outcomes in the subset of patients who underwent surgery after neoadjuvant SBRT. METHODS: Patients with borderline resectable or locally-advanced pancreatic adenocarcinoma who were treated with SBRT followed by resection were included. Chemotherapy was to the discretion of the medical oncologist and preceded SBRT for most patients. RESULTS: Twelve patients met inclusion criteria. Most (92%) received neoadjuvant chemotherapy, and gemcitabine/capecitabine was most frequently utilized (n = 7). Most were treated with fractionated SBRT to 36 Gy/3 fractions (n = 7) and the remainder with single fraction to 24 Gy (n = 5). No grade 3+ acute toxicities attributable to SBRT were found. Two patients developed post-surgical vascular complications and one died secondary to this. The mean time to surgery after SBRT was 3.3 months. An R0 resection was performed in 92% of patients (n = 11/12). In 25% (n = 3/12) of patients, a complete pathologic response was achieved, and an additional 16.7% (n = 2/12) demonstrated <10% viable tumor cells. Kaplan-Meier estimated median progression free survival is 27.4 months. Overall survival is 92%, 64% and 51% at 1-, 2-, and 3-years. CONCLUSIONS: This study reports the pathologic response in patients treated with neoadjuvant chemotherapy and SBRT for borderline resectable and locally-advanced pancreatic cancer. In our experience, 92% achieved an R0 resection and 41.7% of patients demonstrated either complete or extensive pathologic response to treatment. The results of a phase II study of this novel approach will be forthcoming.