A general framework to develop a radiomic fingerprint for progression-free survival in cervical cancer.

PURPOSE: Treatment of locally advanced cervical cancer patients includes chemoradiation followed by brachytherapy. Our aim is to develop a delta radiomics (DRF) model from MRI-based brachytherapy treatment and assess its association with progression free survival (PFS). MATERIALS AND METHODS: A retrospective analysis of FIGO stage IB- IV cervical cancer patients between 2012 and 2018 who were treated with definitive chemoradiation followed by MRI-based intracavitary brachytherapy was performed. Clinical factors together with 18 radiomic features extracted from different radiomics matrices were analyzed. The delta radiomic features (DRFs) were extracted from MRI on the first and last brachytherapy fractions. Support Vector Machine (SVM) models were fitted to combinations of 2-3 DRFs found significant after Spearman correlation and Wilcoxon rank sum test statistics. Additional models were tested that included clinical factors together with DRFs. RESULTS: A total of 39 patients were included in the analysis with a median patient age of 52 years. Progression occurred in 20% of patients (8/39). The significant DRFs using two DRF feature combinations was a model using auto correlation (AC) and sum variance (SV). The best performing three feature model combined mean, AC & SV. Additionally, the inclusion of FIGO stages with the 2- and 3 DRF combination model(s) improved performance compared to models with only DRFs. However, all the clinical factor + DRF models were not significantly different from one another (all AUCs were 0.77). CONCLUSIONS: Our study shows promising evidence that radiomics metrics are associated with progression free survival in cervical cancer.

Considerations for pharmacologic thromboprophylaxis following inpatient brachytherapy for gynecologic malignancies.

PURPOSE: Brachytherapy irradiation carries risks of both bleeding and venous thromboembolism (VTE). No screening or management recommendations for VTE in this setting have been developed. Our study aims to understand the incidence of VTE, compile published anticoagulation guidelines, and call for future guidelines to address thromboprophylaxis in this population. METHODS AND MATERIALS: A retrospective, single institution study of patients undergoing brachytherapy irradiation between 2012 and 2022 was undertaken. We analyzed 2 cohorts: 87 patients undergoing brachytherapy with an inpatient admission, and 66 patients assessed for risk of VTE or bleeding after discharge from an inpatient admission for brachytherapy. Caprini risk scores were calculated for each patient, and statistical analyses were performed. RESULTS: Eighty-seven patients were included, and 25% had a VTE diagnosis. Forty-seven (54%) of patients included underwent brachytherapy as definitive treatment of cervical cancer, and 16 (18%) received brachytherapy irradiation to treat recurrent endometrial cancer. In the cohort of 66 patients assessed for risk of VTE or bleeding after brachytherapy discharge, 23 (34.8%) were discharged with thromboprophylaxis, and 43 (65.2%) were discharged without thromboprophylaxis. None of the patients discharged on thromboprophylaxis were diagnosed with a VTE within 90 days of discharge after brachytherapy, whereas 3 of 43 (7%) discharged without thromboprophylaxis were diagnosed with a VTE, OR and 95% CI: 0.25 (0.01-5.29), p = 0.37. Of the 23 patients discharged on thromboprophylaxis, 1 was readmitted for bleeding OR and 95% CI: 5.8 (0.22-155.18), p = 0.29. The median Caprini score was 11. CONCLUSIONS: VTE is a common occurrence in patients undergoing brachytherapy. Patients undergoing brachytherapy irradiation who require inpatient admission represent a unique population, and specialty organizations should develop consensus recommendations to address these clinical challenges.

Overcoming Burnout and Promoting Wellness in Radiation Oncology: A Report From the ACR Commission on Radiation Oncology.

Burnout, defined by the presence of emotional exhaustion, depersonalization, and decreased sense of personal accomplishment, impacts a significant portion of radiation oncologists. This has been exacerbated by the COVID-19 pandemic, is notably worse for women, and has been identified as an international concern. Key contributors to burnout within radiation oncology include inadequate clinical and administrative support, imbalanced personal and professional lives including time with family and for self-care, decreased job satisfaction secondary to increased electronic medical record and decreased patient time, unsupportive organizational culture, lack of transparency from leadership and inclusion in administrative decisions, emotionally intensive patient interactions, challenges within the radiation oncology workforce, financial security related to productivity-based compensation and increasing medical training-related debt, limited education on wellness, and fear of seeking mental health services due to stigma and potential negative impacts on the trajectory of one's career. Limited data exist to quantify the impacts of these factors on the overall levels of burnout within radiation oncology specifically, and additional efforts are needed to understand and address root causes of burnout within the field. Strategies should focus on improving the systems in which physicians work and providing the necessary skills and resources to thrive in high-stress, high-stakes work environments.

Access to Radiation Therapy and Related Clinical Outcomes in Patients With Cervical and Breast Cancer Across Sub-Saharan Africa: A Systematic Review.

PURPOSE: To better understand the barriers to accessing standard-of-care radiation therapy (RT) for breast and cervical cancer in sub-Saharan Africa and their impact on outcomes. METHODS: A comprehensive literature search was completed with a medical librarian. Articles were screened by title, abstract, and full text. Included publications were analyzed for data describing barriers to RT access, available technology, and disease-related outcomes, and further grouped into subcategories and graded according to predefined criteria. RESULTS: A total of 96 articles were included: 37 discussed breast cancer, 51 discussed cervical cancer, and eight discussed both. Financial access was affected by health care system payment models and combined burdens of treatment-related costs and lost wages. Staffing and technology shortages limit the ability to expand service locations and/or increase capacity within existing centers. Patient factors including use of traditional healers, fear of stigma, and low health literacy decrease the likelihood of early presentation and completion of therapies. Survival outcomes are worse than most high- and middle-income countries and are affected by many factors. Side effects are similar to other regions, but these findings are limited by poor documentation capabilities. Access to palliative RT is more expeditious than definitive management. RT was noted to lead to feelings of burden, lower self-esteem, and worsened quality of life. CONCLUSION: Sub-Saharan Africa represents a diverse region with barriers to RT that differ on the basis of funding, available technology and staff, and community populations. Although long-term solutions must focus on building capacity by increasing the number of treatment machines and providers, short-term improvements should be implemented, such as interim housing for traveling patients, increased community education to reduce late-stage diagnoses, and use of virtual visits to avoid travel.

Treatment of cervical cancer: overcoming challenges in access to brachytherapy.

INTRODUCTION: Brachytherapy is an essential component of the cervical cancer treatment paradigm as it contributes to improved clinical outcomes and overall survival. Yet brachytherapy remains globally underutilized, with disparities in access at both national and international levels. AREAS COVERED: The review explores current brachytherapy utilization practices and efforts being undertaken to address barriers to implementation in low-, middle-, and high-income countries, and how these efforts are projected to impact future brachytherapy access. The content presented is based on a review of published literature and the authors' collective clinical experiences. EXPERT OPINION: There exists a tremendous opportunity to expand access to essential brachytherapy services for women with cervical cancer. Many national and international brachytherapy efforts exist; yet it remains imperative that such focused efforts continue to grow and provide further access to this critical treatment modality for women in need worldwide.

Magnetic Resonance Guided Radiation Therapy for Pancreatic Adenocarcinoma, Advantages, Challenges, Current Approaches, and Future Directions.

INTRODUCTION: Pancreatic adenocarcinoma (PAC) has some of the worst treatment outcomes for any solid tumor. PAC creates substantial difficulty for effective treatment with traditional RT delivery strategies primarily secondary to its location and limited visualization using CT. Several of these challenges are uniquely addressed with MR-guided RT. We sought to summarize and place into context the currently available literature on MR-guided RT specifically for PAC. METHODS: A literature search was conducted to identify manuscript publications since September 2014 that specifically used MR-guided RT for the treatment of PAC. Clinical outcomes of these series are summarized, discussed, and placed into the context of the existing pancreatic literature. Multiple international experts were involved to optimally contextualize these publications. RESULTS: Over 300 manuscripts were reviewed. A total of 6 clinical outcomes publications were identified that have treated patients with PAC using MR guidance. Successes, challenges, and future directions for this technology are evident in these publications. MR-guided RT holds theoretical promise for the treatment of patients with PAC. As with any new technology, immediate or dramatic clinical improvements associated with its use will take time and experience. There remain no prospective trials, currently publications are limited to small retrospective experiences. The current level of evidence for MR guidance in PAC is low and requires significant expansion. Future directions and ongoing studies that are currently open and accruing are identified and reviewed. CONCLUSIONS: The potential promise of MR-guided RT for PAC is highlighted, the challenges associated with this novel therapeutic intervention are also reviewed. Outcomes are very early, and will require continued and long term follow up. MR-guided RT should not be viewed in the same fashion as a novel chemotherapeutic agent for which dosing, administration, and toxicity has been established in earlier phase studies. Instead, it should be viewed as a novel procedural intervention which must be robustly tested, refined and practiced before definitive conclusions on the potential benefits or detriments can be determined. The future of MR-guided RT for PAC is highly promising and the potential implications on PAC are substantial.

Impact of Concurrent Coincident Use of Metformin During Lung Stereotactic Body Radiation Therapy.

Introduction Recent data suggest synergy of chemoradiotherapy and metformin in locally-advanced non-small cell lung cancer (NSCLC). It remains unclear if similar synergy exists with stereotactic lung body radiation therapy (SBRT) and metformin. We analyzed the role of metformin on progression-free survival (PFS) and toxicity in the setting of lung SBRT. Methods We identified 31 patients on metformin-treated with SBRT for early-stage NSCLC. Eighty-nine similarly treated patients were chosen as controls. Kaplan-Meier method was used to estimate cumulative PFS probabilities. Results Median follow-up was 30.7 months. Forty-two patients had diabetes, 31 (74%) of which were taking metformin concurrent with SBRT. Median PFS for metformin-users vs. metformin non-users was 36.4 months vs 48.9 months, respectively (p = 0.29). Among diabetic patients, median PFS for metformin users was 36.4 months and was unobserved for non-users (p= 0.40). On univariable analysis, male sex (p = 0.03) and tumor size (p = 0.01) were associated with the risk of progression or death; use of metformin was not significant (p = 0.34). There was no difference in grade ≥2 radiation pneumonitis between metformin users vs non-users (p = 0.51) Conclusion In this retrospective sample of lung SBRT patients, we did not detect a meaningful effect of concurrent metformin use on PFS. Since SBRT and conventional RT may have different cell kill mechanisms, the previously described beneficial effects of metformin may not apply in a hypofractionated setting. These results should be validated in an independent dataset, and we await the results of ongoing clinical trials.

Pretreatment Factors Influencing Radiation Pneumonitis after Stereotactic Body Radiation Therapy in the Treatment of Lung Cancer.

Objective Radiation pneumonitis (RP) is a dose-limiting toxicity that affects the treatment of lung cancer. Data on factors predictive of developing symptomatic RP after stereotactic body radiation therapy (SBRT) are limited. We reviewed data to identify pretreatment factors predictive of the development of symptomatic RP in patients' lung cancer treated with SBRT. Methods Data were collected on 296 patients treated with SBRT for lung cancer. Factors available at time of consultation were analyzed for the development of symptomatic RP, defined as CTCAE v. 4.0 ≥ Grade 2. The factors analyzed included patient demographic, tumor-specific, and pretreatment pulmonary function data. Univariate and multivariate analyses were performed to assess for predictive factors. Results Median follow-up was 22 months. The rate of symptomatic RP was 16%. Univariate analysis showed an increased rate of symptomatic RP with treatments to the right lung (22% vs. 9%, p = 0.007), driven primarily by an increased rate of symptomatic RP when treating the right lower lobe (RLL) vs. other lobes (31 vs. 13%, p = 0.03). Patients with a history of prior lung directed therapy were also more likely to develop symptomatic RP (12% vs. 24%, p = 0.008). These statistical differences were retained on multivariate analysis. Conclusion SBRT to the right lung, especially the RLL, and to patients with a history of prior lung-directed therapy increases the risk of developing symptomatic RP after SBRT. Further studies on ways to predict and prevent symptomatic RP are needed.

Prognostic Significance of Nuclear Factor Kappa B Expression in Locally Advanced Cervical Cancer Patients Treated Definitively With Concurrent Chemoradiation.

OBJECTIVES: Nuclear factor kappa B (NFkB) is a transcription factor shown to confer treatment resistance in tumors. A previous report suggested an association between pretreatment NFkB and poorer outcomes for cervical cancer patients treated with chemoradiation therapy (CRT). We aimed to validate their findings in a larger patient cohort. MATERIALS AND METHODS: This Institutional Review Board approved study included patients with locally advanced cervical cancer patients treated with CRT. Evaluation of both nuclear and cytoplasmic immunoreactivity for NFkB was scored semiquantitatively by 3 pathologists. Cytoplasmic positivity incorporated both the intensity and percentage of immunoreactivity in invasive carcinoma (H-score), whereas nuclear positivity was assessed by percentage of positive cells. Outcomes were stratified by NFkB overexpression and tumor characteristics. Overall survival (OS), progression-free survival (PFS), distant metastases-free survival (DMFS), and local regional control (LC) were obtained using Kaplan-Meier and differences between groups were evaluated by the log-rank test. Hazard ratios were obtained using Cox regression for both univariate and multivariate analyses. RESULTS: The mean age was 51 years old and most (78.57%) had locally advanced disease. Five-year OS, PFS, LC, and DMFS in the entire cohort were 57.18% (confidence interval [CI], 34.06%-74.82%), 48.07% (CI, 25.50%-67.52%), 72.11% (CI, 49.96%-85.73%), and 62.85% (CI, 36.33%-80.82%), respectively. There was no significant association between NFkB expression (H-index ≥180) and 3-year and 5-year OS (P-value=0.34), PFS (P-value=0.21), LC (P-value=0.86), or DMFS (P-value=0.18). CONCLUSIONS: Our study demonstrated that cytoplasmic NFkB-p65 expression (H-index ≥180) was associated with a nonstatistically significant trend toward poor clinical outcomes in locally advanced cervical cancer patients treated definitively with CRT.

Impact on treatment time of MRI-based brachytherapy in two implants (4 doses) compared with CT-based brachytherapy in five implants for cervical cancer.

PURPOSE: Concurrent chemoradiotherapy and brachytherapy is the standard of care for locally advanced cervical cancer. Brachytherapy is an integral part of treatment and has improved overall survival. Research is needed to ascertain the planning modalities and schedules to best use resources and optimize treatment time course. We hypothesized that MRI-based brachytherapy when delivered with the described regimen would not prolong, and potentially shorten, overall treatment time as compared with CT-based brachytherapy. METHODS AND MATERIALS: This study was a single-institution retrospective review within the years 2008 through 2018. Patients with cervical cancer of any stage who underwent definitive chemoradiotherapy and either CT- or MRI-based brachytherapy were included. The primary outcome variable for this study was time (in days). Overall treatment time was defined as the number of days from the first until the last day of radiotherapy. Univariate analysis was performed using Stata statistical software. RESULTS: External beam radiotherapy doses were generally 45-50.4 Gy. CT-based and MRI-based brachytherapy were performed in 55 and 49 patients, respectively. The median treatment time for brachytherapy with CT-based planning was 19.0 days and with MRI-based planning was 9.0 days (p < 0.001). The median treatment time for total radiation therapy with CT-based planning was 53 days, and with MRI-based planning was 50 days (p = 0.781). CONCLUSIONS: This study found that MRI-based brachytherapy, when performed with the proposed regimen, did not prolong overall treatment time and significantly decreased time to complete brachytherapy in comparison with CT-based brachytherapy on nonconsecutive days. This regimen favorably impacts timely completion of treatment and uses MRI resources well within the construct of our institution.

Predictors of Distant Failure After Stereotactic Body Radiation Therapy for Stages I to IIA Non-Small-Cell Lung Cancer.

PURPOSE: The use of stereotactic body radiation therapy (SBRT) has emerged as an effective treatment modality for patients with early-stage non-small-cell lung cancer (NSCLC), with excellent local control rates. Despite this, there is a predominant pattern of distant failure. We sought to identify factors that help predict which patients with stages I to IIA NSCLC treated with SBRT are at highest risk of distant failure, so that we may utilize these factors in the future to help determine which patients may benefit from the addition of systemic therapies. PATIENTS AND METHODS: We retrospectively reviewed 292 patients treated with SBRT for early stage NSCLC from 2006 to 2016 at 2 institutions. Patients were classified by T stage, tumor size, location and histology, pretreatment positron emission tomography/computed tomography (PET/CT) standardized uptake value (SUV), smoking status, and age. The primary endpoint of the study was distant failure. We aimed to analyze if patient characteristics could be identified that predicted for distant failure through the use of competing risk analysis. RESULTS: The median follow-up was 21.9 months. The median dose of radiation and fractionation delivered was 50 Gy (range, 45-65 Gy) in 5 fractions (range, 3-13 fractions). The median patient age was 72.8 years (interquartile range, 65.4-79.7 years). The 2-year distant failure was 22.0%, and overall survival at 2 years was found to be 61.0%. For every 1-year increase in patient age, the hazard of distant failure at any given time was 3% lower (hazard ratio, 0.97; 95% confidence interval, 0.94-0.99; P = .04). None of the remaining characteristics emerged as significant risk factors for distant failure on univariable or multivariable analysis. CONCLUSIONS: Overall, our cohort had distant failure and survival rates comparable with what has been described in the literature. Although we were unable to identify factors outside of age that correlated to risk of distant failure, this topic warrants further investigation, as distant failure is the primary pattern of failure with SBRT when used as the primary management for early-stage NSCLC. Additional molecular studies are needed to further inform on the role of systemic therapy in patients with early-stage NSCLC to improve clinical outcomes.

Multi-institutional Analysis of Vaginal Brachytherapy Alone for Women With Stage II Endometrial Carcinoma.

PURPOSE: To investigate the survival endpoints in women with International Federation of Gynecology and Obstetrics (FIGO) stage II endometrial cancer who received adjuvant vaginal brachytherapy (VBT) alone using multi-institutional pooled data. METHODS AND MATERIALS: We performed a multi-institutional analysis of surgically staged patients with FIGO stage II endometrioid-type endometrial cancer treated with VBT alone. Patient, tumor, and treatment characteristics were collected and analyzed. Univariable and multivariable frailty survival models were performed to assess clinicopathologic risk factors for recurrence and death. RESULTS: One hundred six patients were included (92 VBT alone and 14 VBT with chemotherapy) with median follow-up of 39.0 months. Pelvic node dissection was performed in 89.6% of patients. One hundred four patients (98.1%) and 2 patients (1.9%) had microscopic and macroscopic cervical stromal invasion, respectively. Grade 1 or 2 disease occurred in 88.6% of patients. For patients treated with VBT without chemotherapy, the 5-year estimates of vaginal failure, pelvic nodal failure, and distant metastases were 2.6%, 4.2%, and 7.2%, respectively. Five-year progression-free survival and overall survival were 74.0% and 76.2%, respectively. On univariable and multivariable models for progression-free survival, increasing age and lack of pelvic node resection were hazardous (P < .05). CONCLUSIONS: Vaginal and pelvic failure rates were low in this selected population of stage II patients receiving adjuvant VBT without external beam radiation therapy. It is reasonable to consider adjuvant VBT alone in selected patients with grade 1 or 2 disease and microscopic cervical stromal invasion who underwent pelvic lymphadenectomy.

Cost in perspective: direct assessment of American market acceptability of Co-60 in gynecologic high-dose-rate brachytherapy and contrast with experience abroad.

PURPOSE: While Ir-192 remains the mainstay isotope for gynecologic high-dose-rate (HDR) brachytherapy in the U.S., Co-60 is used abroad. Co-60 has a longer half-life than Ir-192, which may lead to long-term cost savings; however, its higher energy requires greater shielding. This study analyzes Co-60 acceptability based on a one-time expense of additional shielding and reports the financial experience of Co-60 in Peru's National Cancer Institute, which uses both isotopes. MATERIAL AND METHODS: A nationwide survey was undertaken assessing physician knowledge of Co-60 and willingness-to-pay (WTP) for additional shielding, assuming a source more cost-effective than Ir-192 was available. With 440 respondents, 280 clinicians were decision-makers and provided WTPs, with results previously reported. After completing a shielding report, we estimated costs for shielding expansion, noting acceptability to decision makers' WTP. Using activity-based costing, we note the Peruvian fiscal experience. RESULTS: Shielding estimates ranged from $173,000 to $418,000. The percentage of respondents accepting high-density modular or lead shielding (for union and non-union settings) were 17.5%, 11.4%, 3.9%, and 3.2%, respectively. Shielding acceptance was associated with greater number of radiation oncologists in a respondent's department but not time in practice or the American Brachytherapy Society membership. Peru's experience noted cost savings with Co-60 of $52,400 annually. CONCLUSIONS: By comparing the cost of additional shielding for a sample institution's HDR suite with radiation oncologists' WTP, this multi-institutional collaboration noted < 20% of clinicians would accept additional shielding. Despite low acceptability in the US, Co-60 demonstrates cost-favorability in Peru and may similarly in other locations.

Bladder-Preserving Therapy Patterns of Care: A Survey of US Radiation Oncologists.

PURPOSE: Clinical trials have demonstrated the efficacy of bladder-preserving chemoradiation therapy (BPT) in muscle-invasive bladder cancer but have differed in the radiation therapy dose/fractionations, radiation therapy targets, and concurrent chemotherapy regimens used. No data exist on the technical and practical approaches actually used in clinical practice throughout the United States when delivering BPT. We performed a survey to explore radiation oncologists' practice patterns. METHODS AND MATERIALS: We conducted an electronic survey of US radiation oncologists regarding the management of patients with cT2-3N0M0 transitional cell muscle-invasive bladder cancer. The instrument included questions regarding the types of patients treated with BPT, as well as several aspects of treatment delivery. Descriptive statistics were reported for all responses. Pearson χ2 tests were used for univariate analysis. RESULTS: In total, 277 physicians completed our survey. Most respondents (58%) stated that they only treated 1 to 3 patients in the prior year. Seventy-four percent of respondents primarily treated patients deemed unfit for cystectomy, while only 28% saw patients prior to cystectomy for consultation to discuss BPT. The majority of radiation oncologists used conventional fractionation (91%) instead of hypofractionation (7.6%), but more variability existed for radiation therapy targets. Sixty percent used a small pelvis field, 29% used a whole-pelvis field, and 12% treated the bladder only. There was increased use of hypofractionation (29%) and bladder-only radiation therapy (34%) in patients who were not candidates for cystectomy or chemotherapy (P<.001). Cisplatin-based concurrent chemotherapy was most commonly preferred (89%). In non-cisplatin candidates, most respondents preferred 5-fluorouracil plus mitomycin C (32%) or carboplatin (32%). Intensity modulated radiation therapy use and midtreatment cystoscopic re-evaluation were variable, while hyperfractionation use was low. CONCLUSIONS: Our study describes radiation oncologists' practice patterns for patients undergoing BPT. Although there are areas of consistency, variability exists in many technical and practical aspects of treatment delivery. Further research and education are needed to determine the optimal radiation therapy target, dose/fractionation, and concurrent chemotherapy regimen.

A national survey of HDR source knowledge among practicing radiation oncologists and residents: Establishing a willingness-to-pay threshold for cobalt-60 usage.

PURPOSE: Ir-192 is the predominant source for high-dose-rate (HDR) brachytherapy in United States markets. Co-60, with longer half-life and fewer source exchanges, has piloted abroad with comparable clinical dosimetry but increased shielding requirements. We sought to identify practitioner knowledge of Co-60 and establish acceptable willingness-to-pay (WTP) thresholds for additional shielding requirements for use in future cost-benefit analysis. METHODS AND MATERIALS: A nationwide survey of U.S. radiation oncologists was conducted from June to July 2015, assessing knowledge of HDR sources, brachytherapy unit shielding, and factors that may influence source-selection decision-making. Self-identified decision makers in radiotherapy equipment purchase and acquisition were asked their WTP on shielding should a more cost-effective source become available. RESULTS: Four hundred forty surveys were completed and included. Forty-four percent were ABS members. Twenty percent of respondents identified Co-60 as an HDR source. Respondents who identified Co-60 were significantly more likely to be ABS members, have attended a national brachytherapy conference, and be involved in brachytherapy selection. Sixty-six percent of self-identified decision makers stated that their facility would switch to a more cost-effective source than Ir-192, if available. Cost and experience were the most common reasons provided for not switching. The most common WTP value selected by respondents was <$25,000. CONCLUSIONS: A majority of respondents were unaware of Co-60 as a commercially available HDR source. This investigation was novel in directly assessing decision makers to establish WTP for shielding costs that source change to Co-60 may require. These results will be used to establish WTP threshold for future cost-benefit analysis.

Non-dialysis dependent chronic kidney disease is associated with high total and out-of-pocket healthcare expenditures.

BACKGROUND: Previous studies have documented the high costs of non-dialysis dependent chronic kidney disease (CKD) but out-of-pocket healthcare expenditures remain poorly explored. This study described total direct and out-of-pocket expenditures for adults with non-dialysis dependent CKD and compared expenditures with those for cancer or stroke. METHODS: This study used data from the 2011-2013 Medical Expenditure Panel Survey, a national survey of healthcare expenditures in the U.S. POPULATION: Expenditures were determined for adults with the following chronic diseases: CKD defined by 585 ICD9 codes (n = 52), cancer (colon, breast or bronchus/lung) (n = 870), or stroke (n = 1104). These represent adults who were aware of their conditions or visited a healthcare provider for the condition during the study period. Generalized linear models were used to estimate the marginal effects of CKD, cancer or stroke on adjusted expenditures compared to adults without CKD, cancer or stroke (n = 72,241) while controlling for demographics and co-morbidities and incorporating the sample weights of the complex survey design. RESULTS: The mean age for group with CKD, cancer or stroke was 65.5, 66.1, and 68.2 years, respectively, while mean age for group without CKD, cancer or stroke was 47.8 years. Median values of total direct and out of pocket healthcare expenditures ranged from as high as $12,877 (Interquartile Range [IQR] $5031-$19,710) and $1439 ($688-$2732), respectively, with CKD, to as low as $1189 (IQR $196-$4388) and $226 (IQR $20-$764) in the group without CKD, cancer or stroke. After adjusting for demographics and comorbidities, the adjusted difference in total direct healthcare expenditures was $4746 (95% CI $1775-$7718) for CKD, $8608 (95% CI $6167-$11,049) for cancer and $5992 (95% CI $4208-$7775) for stroke vs. group without CKD, cancer or stroke. Adjusted difference in out-of-pocket healthcare expenditures was highest for adults with CKD ($760; 95% CI 0-$1745) and was larger than difference noted for cancer ($419; 95% CI 158-679) or stroke ($246; 95% CI 87-406) relative to group without CKD, cancer or stroke. CONCLUSIONS: Total and out of pocket health expenditures for adults with non-dialysis dependent CKD are high and may be equal to or higher than expenditures incurred by adults with cancer or stroke.

Local control dependence on consecutive vs. nonconsecutive fractionation in lung stereotactic body radiation therapy.

BACKGROUND: Recent reports demonstrate impaired tumor re-oxygenation 24-48h after stereotactic body radiation therapy (SBRT), suggesting that non-consecutive treatment delivery may be advantageous. To test this hypothesis clinically, we compared local control in patients treated in consecutive daily fractions vs. nonconsecutive fractions. METHODS: We retrospectively reviewed 107 lung SBRT patients (117 tumors) treated for T1-T2N0 NSCLC with LINAC based SBRT (50 or 60Gy/5fractions). Patients were characterized as having been treated in consecutive daily fractions vs. in non-consecutive fractions. Local control, survival and toxicity end points (CTCAE V4.0) were compared. Propensity score matching and Cox regression analyses were performed in order to determine the effect of fractionation on local control. RESULTS: With a median follow up of 23.7months, 3-year local control was superior at 93.3% vs. 63.6% in the non-consecutive and consecutive group, respectively (p=0.001). Multivariate analysis and propensity score matching showed that consecutive fractionation was an independent predictor of local failure. Overall survival trended toward improvement in the non-consecutive group, but this was not statistically significant (p=0.188). Development of any grade 2 toxicity was not significantly different between the two groups (p=0.75). CONCLUSION: Five-fraction SBRT delivered over non-consecutive days imparts superior LC and similar toxicity compared to consecutive fractionation. These results should be validated in independent datasets and in a prospective fashion.