Beant S. Gill

MRI-Guided High–Dose-Rate Intracavitary Brachytherapy for Treatment of Cervical Cancer: The University of Pittsburgh Experience

PURPOSE Image-based brachytherapy is increasingly used for gynecologic malignancies. We report early outcomes of magnetic resonance imaging (MRI)-guided brachytherapy. METHODS AND MATERIALS Consecutive patient cases with FIGO stage IB1 to IVA cervical cancer treated at a single institution were retrospectively reviewed. All patients received concurrent cisplatin with external beam radiation therapy along with interdigitated high-dose-rate intracavitary brachytherapy. Computed tomography or MRI was completed after each application, the latter acquired for at least 1 fraction. High-risk clinical target volume (HRCTV) and organs at risk were identified by Groupe Européen de Curiethérapie and European SocieTy for Radiotherapy and Oncology guidelines. Doses were converted to equivalent 2-Gy doses (EQD2) with planned HRCTV doses of 75 to 85 Gy. RESULTS From 2007 to 2013, 128 patients, median 52 years of age, were treated. Predominant characteristics included stage IIB disease (58.6%) with a median tumor size of 5 cm, squamous histology (82.8%), and no radiographic nodal involvement (53.1%). Most patients (67.2%) received intensity modulated radiation therapy (IMRT) at a median dose of 45 Gy, followed by a median brachytherapy dose of 27.5 Gy (range, 25-30 Gy) in 5 fractions. At a median follow up of 24.4 months (range, 2.1-77.2 months), estimated 2-year local control, disease-free survival, and cancer-specific survival rates were 91.6%, 81.8%, and 87.6%, respectively. Predictors of local failure included adenocarcinoma histology (P<.01) and clinical response at 3 months (P<.01). Among the adenocarcinoma subset, receiving HRCTV D90 EQD2 ≥84 Gy was associated with improved local control (2-year local control rate 100% vs 54.5%, P=.03). Grade 3 or greater gastrointestinal or genitourinary late toxicity occurred at a 2-year actuarial rate of 0.9%. CONCLUSIONS This study constitutes one of the largest reported series of MRI-guided brachytherapy in North America, demonstrating excellent local control with acceptable morbidity. Dose escalation may be warranted when feasible for adenocarcinomas to offset the risk of local failure.

Treatment Selection and Survival Outcomes in Early-Stage Diffuse Large B-Cell Lymphoma: Do We Still Need Consolidative Radiotherapy?

PURPOSE The choice between chemotherapy alone and chemotherapy plus consolidative radiotherapy (RT) for diffuse large B-cell lymphoma (DLBCL) remains controversial. We aimed to define factors affecting treatment selection and the resulting survival outcomes. PATIENTS AND METHODS Using the National Cancer Data Base, we identified 59,255 patients with stages I and II DLBCL treated with multiagent chemotherapy alone or chemotherapy plus consolidative RT between 1998 and 2012. Univariable and multivariable analyses were performed to identify sociodemographic, treatment, and tumor characteristics predictive of overall survival (OS) and treatment use. Propensity-adjusted Cox proportional hazard ratios for survival were used to account for indication bias. RESULTS Of the 59,255 patients with DLBCL enrolled onto the study, 46% had stage II disease, 42% had extranodal disease, and 58% were more than 60 years of age. Only 39% received combined-modality therapy, and this proportion significantly declined from 47% in 2000 to 32% in 2012 (P < .001). Treatment selection was significantly influenced by race, comorbidity, insurance type, education quartile, facility type, age, stage, B symptoms, distance from treatment facility, and year of diagnosis. The median follow-up time was 60 months (interquartile range, 33 to 93). Estimated 5-year and 10-year OS rates were, respectively, 79% and 59% for all patients, 75% and 55% for patients receiving chemotherapy alone, and 82% and 64% for patients receiving combined-modality therapy (P < .001). Even after adjusting for immortal times and indication bias, combined-modality therapy was associated with better OS (HR, 0.66; 95% CI, 0.61 to 0.71; P < .001) than was chemotherapy alone. CONCLUSION Use of consolidative RT after multiagent chemotherapy in DLBCL is decreasing in the modern era. Selection of treatment strategy is affected by both classical prognostic features and socioeconomic factors. Abandonment of combined-modality therapy in favor of chemotherapy alone negatively affects patient survival.

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.

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.

What is the optimal management of early‐stage low‐grade follicular lymphoma in the modern era?

Despite international practice guidelines endorsing radiotherapy (RT) as the preferred initial therapy, treatment approaches vary for patients with early‐stage follicular lymphoma. The authors engaged the National Cancer Data Base to analyze patterns of care and survival outcomes for patients with early‐stage follicular lymphoma in the era of modern therapy.

Anaplastic thyroid cancer: Prognostic factors, patterns of care, and overall survival

Anaplastic thyroid cancer (ATC) represents a rare, aggressive malignancy. We analyzed factors predictive for overall survival (OS) and treatment modality utilization.

Primary radiotherapy for nonsurgically managed Stage I endometrial cancer: Utilization and impact of brachytherapy

PURPOSE The National Cancer Data Base (NCDB) was analyzed to evaluate practice patterns and the impact of radiotherapy modalities for endometrial cancer treated with primary radiotherapy. METHODS AND MATERIALS The NCDB was queried for Stage I endometrioid adenocarcinoma patients treated with primary radiotherapy without surgery from 1998 to 2006. Brachytherapy (BT) utilization factors were established using multivariable logistic regression. Log-rank and Cox proportional hazards modeling were used to assess variables impacting survival. RESULTS A total of 853 patients were analyzed: 23.7%, 31.3%, and 45.0% received BT alone, external beam radiotherapy (EBRT) and BT, or EBRT alone. The BT utilization ranged from 40.5% to 51.9% over time (p=0.70). Lower utilization was associated with advanced age (≥80 years: odds ratio [OR] 0.43, 95% confidence interval [CI] 0.28-0.65, p<0.01) and facilities with volume in the bottom quartile (OR 0.44, 95% CI 0.30-0.66, p<0.01). Utilization was higher among patients living more than 30 miles from the facilities (OR 2.14, 95%CI 1.35-3.42, p<0.01). With 36-month median followup, unadjusted median survivals for EBRT dose of 30Gy or lower, EBRT dose higher than 30Gy, BT, and EBRT+BT were 12.6, 31.1, 44.6, and 57.1 months (p<0.01). After correcting for other factors, higher risk of mortality was seen with EBRT dose of 30Gy or lower (hazard ratio [HR]2.75, 95% CI 1.66-4.55, p<0.01) and EBRT dose higher than 30Gy (HR 1.43, 95% CI 1.07-1.91, p=0.02) compared with EBRT+BT. No difference was seen using BT alone (HR 1.29, 95% CI 0.92-1.79, p=0.14). CONCLUSION BT utilization for nonsurgically managed endometrial cancer remains low with most patients receiving EBRT alone. Despite concerns of overtreatment in a population with competing causes of death, BT appears to improve survival.

Tumor bed radiosurgery following resection and prior stereotactic radiosurgery for locally persistent brain metastasis

Purpose Despite advances in multimodality management of brain metastases, local progression following stereotactic radiosurgery (SRS) can occur. Often, surgical resection is favored, as it frequently provides immediate symptom relief as well as pathological characterization of any residual tumor. Should the pathological specimen contain viable tumor cells, further radiation therapy is an option to sterilize the tumor bed. We evaluated the use of repeat SRS (rSRS) in lieu of whole-brain radiation therapy (WBRT) as a means of improving local control (LC) while minimizing potential toxicity and dose to the normal brain. Materials/methods A retrospective review was performed to identify patients with brain metastases who underwent SRS and then surgical resection for locally recurrent or persistent disease. From 2004 to 2014, 13 consecutive patients or 15 lesions were treated with rSRS after resection, either post-operatively to the tumor bed (n = 10, 66.6%) or after a second local recurrence (n = 5, 33.3%). LC, distant brain failure (DBF), and radiation toxicity were determined using patient records, RECIST criteria v1.1, and CTCAE v4.03. Results At a median follow-up interval of 9.0 months (range 1.8–54.9 months) from time of rSRS, five patients remain alive. Following rSRS, 13 of the 15 (86.6%) lesions were locally controlled with an estimated 100% LC at 6 months and 75% LC at 1 year. However, 11 of the 15 (73.3%) treated lesions developed DBF after rSRS with 3 of 13 patients proceeding to WBRT. Two of 15 (13.3%) resulted in either grade 2 radionecrosis with grade 3 seizures or grade 3 radionecrosis. Conclusion Repeat SRS represents a potential salvage therapy for patients with locally recurrent brain metastases, providing additional tumor control with acceptable toxicity, even in the setting of prior SRS and surgical resection. rSRS may be reasonable to use as an alternative to WBRT in this setting.

Cervical cancer outcome prediction to high-dose rate brachytherapy using quantitative magnetic resonance imaging analysis of tumor response to external beam radiotherapy

BACKGROUND AND PURPOSE In order to assess tumor regression and outcomes, a volumetric analysis was conducted for cervical cancer patients treated with magnetic resonance imaging (MRI)-based image-guided brachytherapy (IGBT). MATERIALS AND METHODS Consecutive patients with FIGO stage IB1-IVA cervical cancer receiving chemoradiation from 2007 to 2013 were identified, excluding patients with perineal template-based interstitial brachytherapy or without undergoing MRI. A ring and tandem applicator±interstitial needles was used. T2-weighted imaging was completed following applicator insertion. Gross tumor volumes (GTVs) were retrospectively contoured: initial GTV (GTV(Pre-EBRT)), GTV at first brachytherapy (GTV(IGBT)) and percent residual GTV at first brachytherapy (% GTV(Residual)). RESULTS Eighty-four patients were identified. With 20.8-month median follow-up, two-year estimates of local control (LC), disease-free survival (DFS) and overall survival (OS) were 91.3, 79.8, and 85.0%, respectively. Multivariate Cox regression revealed adenocarcinoma (HR 5.88, p=0.03) and GTV(IGBT) (HR 1.17, p<0.01) as predictors for local failure. GTV(IGBT)>7.5 cc was associated with inferior 2-year LC (75.0 vs. 96.6%, p<0.01), DFS (42.6 vs. 91.6%, p<0.01) and OS (65.2 vs. 91.5%, p<0.01). No difference in mean HRCTV D(90) EQD(2) was seen between the groups (p=0.61). CONCLUSION Aside from known benefits of IGBT, MRI-based planning allows for assessment of tumor regression and prognosticates patients.

Utility of PET for Radiotherapy Treatment Planning

PET imaging has contributed substantially in oncology by allowing improved clinical staging and guiding appropriate cancer management. Integration with radiotherapy planning via PET/computed tomography (CT) simulation enables improved target delineation, which is paramount for conformal radiotherapy techniques. This article reviews the present literature regarding implications of PET/CT for radiotherapy planning and management.