Sriram Venigalla

Association Between Treatment at High-Volume Facilities and Improved Overall Survival in Soft Tissue Sarcomas

PURPOSEnSoft tissue sarcomas (STS) are rare malignancies that require complex multidisciplinary management. Therefore, facilities with high sarcoma case volume may demonstrate superior outcomes. We hypothesized that STS treatment at high-volume (HV) facilities would be associated with improved overall survival (OS).nnnMETHODS AND MATERIALSnPatients aged ≥18xa0years with nonmetastatic STS treated with surgery and radiation therapy at a single facility from 2004 through 2013 were identified from the National Cancer Database. Facilities were dichotomized into HV and low-volume (LV) cohorts based on total case volume over the study period. OS was assessed using multivariable Cox regression with propensity score-matching. Patterns of care were assessed using multivariable logistic regression analysis.nnnRESULTSnOf 9025 total patients, 1578 (17%) and 7447 (83%) were treated at HV and LV facilities, respectively. On multivariable analysis, high educational attainment, larger tumor size, higher grade, and negative surgical margins were statistically significantly associated with treatment at HV facilities; conversely, black race and non-metropolitan residence were negative predictors of treatment at HV facilities. On propensity score-matched multivariable analysis, treatment at HV facilities versus LV facilities was associated with improved OS (hazard ratio, 0.87, 95% confidence interval, 0.80-0.95; P = .001). Older age, lack of insurance, greater comorbidity, larger tumor size, higher tumor grade, and positive surgical margins were associated with statistically significantly worse OS.nnnCONCLUSIONSnIn this observational cohort study using the National Cancer Database, receipt of surgery and radiation therapy at HV facilities was associated with improved OS in patients with STS. Potential sociodemographic disparities limit access to care at HV facilities for certain populations. Our findings highlight the importance of receipt of care at HV facilities for patients with STS and warrant further study into improving access to care at HV facilities.

Trends and Patterns of Utilization of Hypofractionated Postmastectomy Radiotherapy: A National Cancer Database Analysis

Background The acceptance of hypofractionated radiotherapy in treating breast cancer in the breast conservation therapy setting has stimulated interest in hypofractionated postmastectomy radiotherapy (PMRT). We assessed national trends and patterns of utilization of hypofractionated PMRT. Patients and Methods Women 18 years of age or older with breast cancer treated with mastectomy and PMRT to the chest wall with or without regional lymph nodes from 2004 to 2014 were identified from the National Cancer Database. A standard fractionation cohort was defined as patients receiving 180 to 200 cGy per fraction to a total dose of 4500 to 7000 cGy over 5 to 7 weeks, and a hypofractionation cohort was defined as those receiving 250 to 400 cGy per fraction to a total dose of 3000 to 6000 cGy over 2 to 5 weeks. Multivariable logistic regression was used to determine factors associated with hypofractionated PMRT use. Results We identified 113,981 patients who met study criteria. Overall, hypofractionated PMRT use was low (1.1%) although utilization increased over time (P ≤ .001). Older age, greater comorbidity, further distance from treatment facility, treatment at academic facilities, less extensive disease, and recent treatment year were statistically significant predictors of hypofractionation use compared with standard fractionation. Conversely, breast reconstruction and receipt of chemotherapy were negative predictors. Conclusion Because of the absence of high‐level evidence to support its use, hypofractionated PMRT was uncommonly utilized in the United States from 2004 to 2014, although a small increase in use was noted over time. Findings from this study might be useful in designing future studies, and might serve as a baseline for evaluation of future changes in practice patterns. Micro‐Abstract There is growing interest in treating breast cancer with hypofractionated postmastectomy radiotherapy (PMRT). National patterns of hypofractionated PMRT utilization were assessed using the National Cancer Database. Overall, hypofractionated PMRT use was uncommon although it increased over time. Hypofractionated PMRT was used in patients more likely to gain convenience from shorter treatment schedules.

Definitive local therapy is associated with improved overall survival in metastatic cervical cancer

PURPOSEnDefinitive local therapy is often used in metastatic cervical cancer to reduce morbidity associated with local tumor progression. However, the potential benefit of this therapeutic approach has not been rigorously investigated. We hypothesized that definitive local therapy is associated with improved overall survival (OS) in metastatic cervical cancer.nnnMETHODS AND MATERIALSnPatients aged ≥18 years with newly diagnosed metastatic cervical cancer who were treated with chemotherapy were identified from the National Cancer Database. Patients were dichotomized into the following cohorts: definitive local therapy (defined as either concurrent chemoradiation therapy or definitive surgery) or conservative therapy (defined as systemic therapy with or without palliative radiation therapy). The association between definitive local therapy and OS was assessed using propensity score-weighted Cox proportional hazards models. Potential unmeasured confounding was assessed through sensitivity analyses. Factors associated with the receipt of definitive local therapy were identified with multivariable logistic regression.nnnRESULTSnA total of 2838 patients were identified, of whom 1194 (42%) and 1644 (58%) were treated with definitive local and conservative therapy, respectively. Receipt of definitive local therapy was statistically significant, associated with less comorbidity, lower clinical T stage, and node negative disease. Compared with conservative therapy, definitive local therapy was associated with improved OS (hazard ratio: 0.57; 95% confidence interval, 0.52-0.62; P ≤ .001). The median OS rate was 19.2 months in the definitive local therapy cohort and 10.1 months in the conservative therapy cohort. These findings were robust to potential unmeasured confounding in sensitivity analyses and on landmark analyses of patients who survived at least 12 months (hazard ratio: 0.71; 95% confidence interval, 0.62-0.82; P ≤ .001).nnnCONCLUSIONSnDefinitive local therapy is associated with improved OS in patients with metastatic cervical cancer. These findings suggest a novel setting for the use of definitive local therapy in the metastatic setting.

Urinary bladder cancer T-staging from T2-weighted MR images using an optimal biomarker approach.

Magnetic resonance imaging (MRI) is often used in clinical practice to stage patients with bladder cancer to help plan treatment. However, qualitative assessment of MR images is prone to inaccuracies, adversely affecting patient outcomes. In this paper, T2-weighted MR image-based quantitative features were extracted from the bladder wall in 65 patients with bladder cancer to classify them into two primary tumor (T) stage groups: group 1 – T stage < T2, with primary tumor locally confined to the bladder, and group 2 – T stage < T2, with primary tumor locally extending beyond the bladder. The bladder was divided into 8 sectors in the axial plane, where each sector has a corresponding reference standard T stage that is based on expert radiology qualitative MR image review and histopathologic results. The performance of the classification for correct assignment of T stage grouping was then evaluated at both the patient level and the sector level. Each bladder sector was divided into 3 shells (inner, middle, and outer), and 15,834 features including intensity features and texture features from local binary pattern and gray-level co-occurrence matrix were extracted from the 3 shells of each sector. An optimal feature set was selected from all features using an optimal biomarker approach. Nine optimal biomarker features were derived based on texture properties from the middle shell, with an area under the ROC curve of AUC value at the sector and patient level of 0.813 and 0.806, respectively.

Use and Effectiveness of Adjuvant Endocrine Therapy for Hormone Receptor–Positive Breast Cancer in Men

Importance Although adjuvant endocrine therapy confers a survival benefit among females with hormone receptor (HR)–positive breast cancer, the effectiveness of this treatment among males with HR-positive breast cancer has not been rigorously investigated. Objective To investigate trends, patterns of use, and effectiveness of adjuvant endocrine therapy among men with HR-positive breast cancer. Design, Setting, and Participants This retrospective cohort study identified patients in the National Cancer Database with breast cancer who had received treatment from 2004 through 2014. Inclusion criteria for the primary study cohort were males at least 18 years old with nonmetastatic HR-positive invasive breast cancer who underwent surgery with or without adjuvant endocrine therapy. A cohort of female patients was also identified using the same inclusion criteria for comparative analyses by sex. Data analysis was conducted from October 1, 2017, to December 15, 2017. Exposures Receipt of adjuvant endocrine therapy. Main Outcomes and Measures Patterns of adjuvant endocrine therapy use were assessed using multivariable logistic regression analyses. Association between adjuvant endocrine therapy use and overall survival was assessed using propensity score-weighted multivariable Cox regression models. Results The primary study cohort comprised 10 173 men with HR-positive breast cancer (mean [interquartile range] age, 66 [57-75] years). The comparative cohort comprised 961 676 women with HR-positive breast cancer (mean [interquartile range] age, 62 [52-72] years). The median follow-up for the male cohort was 49.6 months (range, 0.1-142.5 months). Men presented more frequently than women with HR-positive disease (94.0% vs 84.3%, Pu2009<u2009.001). However, eligible men were less likely than women to receive adjuvant endocrine therapy (67.3% vs 79.0%; OR, 0.61; 95% CI, 0.58-0.63; Pu2009<u2009.001). Treatment at academic facilities (odds ratio, 1.13; 95% CI, 1.02-1.25; Pu2009=u2009.02) and receipt of adjuvant radiotherapy (odds ratio, 2.83; 95% CI, 2.55-3.15; Pu2009<u2009.001) or chemotherapy (odds ratio, 1.20; 95% CI, 1.07-1.34; Pu2009<u2009.001) were statistically significantly associated with adjuvant endocrine therapy use in men. A propensity score-weighted analysis indicated that relative to no use, adjuvant endocrine therapy use in men was associated with improved overall survival (hazard ratio, 0.70; 95% CI, 0.63-0.77; Pu2009<u2009.001). Conclusions and Relevance There is a sex disparate underuse of adjuvant endocrine therapy among men with HR-positive breast cancer despite the use of this treatment being associated with improved overall survival. Further research and interventions may be warranted to bridge gaps in care in this population.

Disparities in Perioperative Radiation Therapy Use in Elderly Patients With Soft-Tissue Sarcoma

PURPOSEnThe benefit of perioperative radiation therapy in elderly patients with soft-tissue sarcoma (STS) is unclear due to the underrepresentation of elderly patients in clinical trials. We assessed patterns of care and overall survival (OS) associated with perioperative radiation therapy use in this population.nnnMETHODS AND MATERIALSnElderly patients (≥70 years) with high-grade STS who underwent surgery with or without perioperative radiation therapy from 2004 to 2013 were identified from the National Cancer Database. A nonelderly cohort (<70 years) was also identified for secondary comparative analyses. The association between perioperative radiation therapy use and OS was assessed using propensity score-weighted Cox proportional hazards analyses. Relative survival was calculated using national life tables to assess the impact of radiation therapy on estimated sarcoma-specific survival in elderly and nonelderly patients. Patterns of care were assessed using multivariable logistic regression analyses.nnnRESULTSnOf 6978 elderly patients, 3549 (51%) underwent surgery alone, and 740 (11%) and 2,679 (38%) received pre- and postoperative radiation therapy, respectively. Elderly patients received radiation therapy less commonly than did nonelderly patients (49% vs 52%, P < .001) despite presenting with higher grade tumors (grade 3, 86% vs 80%, P < .001) and experiencing more frequent positive surgical margins (23% vs 16%, P < .001). On propensity score-weighted analyses, preoperative (hazard ratio = 0.64, 95% confidence interval: 0.54-0.77, P < .001) and postoperative (hazard ratio = 0.72, 95% confidence interval: 0.67-0.77, P < .001) radiation therapy use was associated with improved OS compared with surgery alone. These associations were robust to landmark analyses of patients surviving at least 12 months. Radiation therapy use resulted in a greater magnitude of 5-year relative survival improvement in elderly than nonelderly patients.nnnCONCLUSIONSnThere is an overall and an age-disparate underuse of perioperative radiation therapy in elderly patients with high-grade STS despite radiation therapy being associated with improved OS. Further research is warranted to minimize gaps in care for elderly patients.

Survival implications of staging lymphadenectomy for non-endometrioid endometrial cancers

PURPOSEnTo determine, in patients with non-endometrioid endometrial carcinoma, 1) survival benefit associated with pelvic lymphadenectomy (LND), 2) survival benefit for para-aortic lymphadenectomy performed in addition to pelvic lymphadenectomy, and 3) association between number of lymph nodes removed and survival.nnnMETHODSnPatients with clinical stage I serous carcinoma, clear cell carcinoma, or carcinosarcoma who underwent hysterectomy from 2010 to 2013 were identified from the National Cancer Database. Hazard ratio (HR) for death was assessed using propensity score-weighted multivariable Cox regression models. Subgroup analyses assessed for differences in risk of death among histologic subtypes.nnnRESULTSn7250 patients met study criteria. 930 (13%) did not undergo LND; 2177 (30%) underwent pelvic LND alone; 4143 (57%) underwent pelvic+para-aortic LND. On propensity score-weighted analysis, pelvic LND was associated with decreased risk of death (HR=0.65, 95% CI: 0.59-0.71) compared to no LND. Pelvic+para-aortic LND was associated with decreased risk of death (HR=0.85, 95% CI: 0.79-0.91) compared to pelvic LND for patients with serous carcinoma. Removal of >15 nodes was independently associated with decreased HR for death (HR=0.86, 95% CI: 0.77-0.96); this association persisted when analysis was limited to patients with node-positive disease (HR=0.78, 95% CI: 0.63-0.95).nnnCONCLUSIONSnLND is associated with survival benefit in patients with non-endometrioid endometrial cancers. Addition of para-aortic LND to pelvic LND may be most beneficial for patients with serous carcinoma. Systematic lymphadenectomy may be associated with survival benefit through detection and microscopic cytoreduction of occult disease.

Comparative Effectiveness of Neoadjuvant Chemoradiation Versus Upfront Surgery in the Management of Recto-Sigmoid Junction Cancer

Micro‐Abstract: The optimal management of patients with locally advanced recto‐sigmoid cancer is unclear. Using the National Cancer Database, we assessed patterns of care and outcomes associated with upfront surgery versus neoadjuvant chemoradiation followed by surgery. Although neoadjuvant chemoradiation was used in a small percentage of patients, its use was associated with more complete resections, a robust pathologic complete response rate, and improved overall survival. Introduction: The optimal management of locally advanced recto‐sigmoid cancer is unclear. Although some experts advocate for upfront surgery, others recommend neoadjuvant chemoradiation followed by surgery. We used the National Cancer Database to characterize patterns‐of‐care and overall survival (OS) associated with these treatment strategies. Patients and Methods: Patients with clinical stage II or III recto‐sigmoid cancer who underwent surgery with or without adjunctive chemotherapy and/or radiotherapy from 2006 to 2014 were identified, and dichotomized into: (1) upfront surgery, and (2) neoadjuvant chemoradiation cohorts. Patterns‐of‐care were assessed using multivariable logistic regression. The association between neoadjuvant chemoradiation use and OS was assessed using Cox proportional hazards analysis with propensity score‐matching. Results: Of 9313 identified patients, 6756 (73%) underwent upfront surgery and 2557 (27%) received neoadjuvant chemoradiation. Treatment at academic facilities and higher clinical T stage were predictors of neoadjuvant chemoradiation use. Compared with upfront surgery, neoadjuvant chemoradiation resulted in fewer positive circumferential resection margins (384 [11%] patients vs. 108 [8%] patients; P = .001), and 478 [18.7%] patients achieved a pathologic complete response at surgery. In propensity score‐matched analysis, neoadjuvant chemoradiation use was associated with improved OS (hazard ratio, 0.79; 95% confidence interval, 0.69–0.90) compared with upfront surgery; 5‐year estimated OS was 77.0% versus 72.0%, respectively. The improvement in OS persisted in landmark analysis of patients who survived at least 12 months. Conclusion: Only a small percentage of patients with locally advanced recto‐sigmoid cancer receive neoadjuvant chemoradiation even though its use might result in improved OS relative to upfront surgery. Prospective research is warranted to validate and standardize therapeutic strategies in patients with recto‐sigmoid cancer.

Radiomics-guided therapy for bladder cancer: Using an optimal biomarker approach to determine extent of bladder cancer invasion from t2-weighted magnetic resonance images

Background Current clinical staging methods are unable to accurately define the extent of invasion of localized bladder cancer, which affects the proper use of systemic therapy, surgery, and radiation. Our purpose was to test a novel radiomics approach to identify optimal imaging biomarkers from T2-weighted magnetic resonance imaging (MRI) scans that accurately classify localized bladder cancer into 2 tumor stage groups (≤T2 vs >T2) at both the patient level and within bladder subsectors. Method and Materials Preoperative T2-weighted MRI scans of 65 consecutive patients followed by radical cystectomy were identified. A 3-layer, shell-like volume of interest (VOI) was defined on each MRI slice: Inner (lumen), middle (bladder wall), and outer (perivesical tissue). An optimal biomarker method was used to identify features from 15,834 intensity and texture properties that maximized the classification of patients into ≤T2 versus >T2 groups. A leave-one-out strategy was used to cross-validate the performance of the identified biomarker feature set at the patient level. The performance of the feature set was then evaluated at the subsector level of the bladder by dividing the VOIs into 8 radial sectors. Results A total of 9 optimal biomarker features were derived and demonstrated a sensitivity, specificity, accuracy of prediction, and area under a receiver operating characteristic curve of 0.742, 0.824, 0.785, and 0.806, respectively, at the patient level and 0.681, 0.788, 0.763, and 0.813, respectively, at the radial sector level. All 9 selected features were extracted from the middle shell of the VOI and based on texture properties. Conclusions An approach to select a small, highly independent feature set that is derived from T2-weighted MRI scans that separate patients with bladder cancer into ≤T2 versus >T2 groups at both the patient level and within subsectors of the bladder has been developed and tested. With external validation, this radiomics approach could improve the clinical staging of bladder cancer and optimize therapeutic management.