Matthew W. Jackson

The impact of postmastectomy and regional nodal radiation after neoadjuvant chemotherapy for clinically lymph node-positive breast cancer: a National Cancer Database (NCDB) analysis

BACKGROUND Following neoadjuvant chemotherapy (NAC), the optimal strategies for postmastectomy radiotherapy (PMRT) and regional nodal irradiation (RNI) after breast-conserving surgery (BCS) are controversial. In this analysis, we evaluate the impact of these radiotherapy (RT) approaches for women with clinically node-positive breast cancer treated with NAC in the National Cancer Database (NCDB). PATIENTS AND METHODS Women with cT1-3 cN1 M0 breast cancer treated with NAC were divided into four cohorts by surgery [Mastectomy (Mast) versus BCS] and post-chemotherapy pathologic nodal status (ypN0 versus ypN+). Overall survival (OS) was estimated using the Kaplan-Meier method and RT approaches were analyzed using the log-rank test, multivariate Cox models, and propensity score-matched analyses. RESULTS From 2003 to 2011, 15 315 cases were identified including 3040 Mast-ypN0, 7243 Mast-ypN+, 2070 BCS-ypN0, and 2962 BCS-ypN+ patients. On univariate analysis, PMRT was associated with improved OS for both Mast-ypN0 (P = 0.019) and Mast-ypN+ (P < 0.001) patients. On multivariate analyses adjusted for factors including age, comorbidity score, cT stage, in-breast pathologic complete response, axillary surgery, ypN stage, estrogen receptor status and hormone therapy, PMRT remained independently associated with improved OS among Mast-ypN0 [hazard ratio (HR) = 0.729, 95% confidence interval (CI) 0.566-0.939, P = 0.015] and Mast-ypN+ patients (HR = 0.772, 95% CI 0.689-0.866, P < 0.001). No differences in OS were observed with the addition of RNI to breast RT for BCS-ypN0 or BCS-ypN+ patients. Propensity score-matched analyses demonstrated identical patterns of significance. On subset analysis, OS was improved with PMRT in each pathologic nodal subgroup (ypN0, ypN1, and ypN2-3) (all P < 0.05). CONCLUSIONS In the largest reported analysis of RT for cN1 patients treated with NAC, PMRT was associated with improved OS for all pathologic nodal subgroups. No OS differences were observed with the addition of RNI to breast RT.

Clinical potential of bevacizumab in the treatment of metastatic and locally advanced cervical cancer: current evidence

The addition of bevacizumab to established therapies for metastatic and locally advanced cervical cancer is an area of evolving research and a potential strategy toward improving historically suboptimal outcomes for women with advanced disease. Bevacizumab, when added to first-line chemotherapy, has now been shown to improve overall survival among women with metastatic cervical cancer, and recent Phase II data suggests it is safe and effective for patients with locally advanced disease treated with curative intent. Here we review the rationale and current evidence for bevacizumab in clinical practice, with an emphasis on the emerging role of bevacizumab in the treatment of metastatic and locally advanced cervical cancer.

Survival Outcomes of Dose-Escalated External Beam Radiotherapy versus Combined Brachytherapy for Intermediate and High Risk Prostate Cancer Using the National Cancer Data Base

PURPOSE We evaluated survival outcomes between dose-escalated EBRT (external beam radiotherapy) vs EBRT plus brachytherapy for intermediate and high risk prostate cancer using NCDB (National Cancer Data Base). MATERIALS AND METHODS Patients with cN0M0 prostate cancer treated from 2004 to 2006 were divided into radiotherapy comparison groups, including EBRT alone (75.6 to 81 Gy) and EBRT (40 to 50.4 Gy) plus brachytherapy with EBRT delivered at 1.8 to 2.0 Gy per fraction. Brachytherapy data were limited to yes/no with no information on modality, dose or schedule. Eligible patients were known to have received androgen deprivation therapy. Overall survival was evaluated using multivariate Cox regression and propensity score matched analyses. RESULTS Of the 20,279 study patients with prostate cancer, including 12,617 at intermediate risk and 7,662 at high risk, 71.3% received EBRT alone and 28.7% received EBRT plus brachytherapy. Median followup was 82 months (range 3 to 120) and median age was 70 years (range 36 to 90). On multivariate analysis compared to EBRT alone (75.6 to 81 Gy) EBRT plus brachytherapy was associated with improved survival (HR 0.75, p <0.001). This significance remained consistent for intermediate and high risk when analyzed separately (HR 0.73 and 0.76, respectively, each p <0.001). However on subset analysis compared to very high dose EBRT alone (79.2 to 81 Gy) in all patients combined EBRT plus brachytherapy was not associated with improved survival (HR 0.91, p = 0.083). CONCLUSION Compared to EBRT (75.6 to 81 Gy) we observed an association of EBRT plus brachytherapy with a decreased risk of death in men with intermediate and high risk prostate cancer. However this association was no longer significant when EBRT doses of 79.2 to 81 Gy were used.

Improved survival with combined modality therapy in the modern era for primary mediastinal B-cell lymphoma.

Primary mediastinal B‐cell lymphoma (PMBCL) is an uncommon lymphoma for which existing data is limited. We utilized the National Cancer Database (NCDB) to evaluate PMBCL and the impact of radiotherapy (RT) on outcomes in the years following FDA approval of rituximab. We queried the NCDB for patients with PMBCL diagnosed from 2006 to 2011 and treated with multiagent chemotherapy. Kaplan–Meier overall survival (OS) estimates, univariate (UVA), and multivariate (MVA) Cox proportional hazards regression analyses were performed. Propensity score matched analysis (PSMA) was performed to account for indication bias and mitigate heterogeneity between treatment groups. 465 patients were identified with a median follow‐up of 36 months. Median age was 36 years; 43% received RT. 5‐year OS for the entire cohort was 87%, and for the no‐RT and RT groups, 83% versus 93%, respectively. On UVA, OS was improved with RT (HR 0.34, P = 0.002). On MVA, RT remained significantly associated with improved OS (HR 0.44, P = 0.028) while Medicaid insurance status and increasing stage remained significantly associated with OS decrement. PSMA confirmed the OS benefit associated with RT. This analysis is the largest PMBCL dataset to date and demonstrates a significant survival benefit associated with RT in patients receiving multiagent chemotherapy in the rituximab era. More than half of patients treated in the United States during this time period did not receive RT. In the absence of phase III data to support omission, combined modality therapy with its associated survival benefit should be the benchmark against which other therapies are compared. Am. J. Hematol. 91:476–480, 2016.

Improved Survival With Radiation Therapy in Stage I-II Primary Mediastinal B Cell Lymphoma: A Surveillance, Epidemiology, and End Results Database Analysis

BACKGROUND Primary mediastinal B cell lymphoma (PMBCL) is an uncommon lymphoma for which trials are few with small patient numbers. The role of radiation therapy (RT) after standard immunochemotherapy for early-stage disease has never been studied prospectively. We used the Surveillance, Epidemiology, and End Results (SEER) database to evaluate PMBCL and the impact of RT on outcomes. METHODS AND MATERIALS We queried the SEER database for patients with stage I-II PMBCL diagnosed from 2001 to 2011. Retrievable data included age, gender, race (white/nonwhite), stage, extranodal disease, year of diagnosis, and use of RT as a component of definitive therapy. Kaplan-Meier overall survival (OS) estimates, univariate (UVA) log-rank and multivariate (MVA) Cox proportional hazards regression analyses were performed. RESULTS Two hundred fifty patients with stage I-II disease were identified, with a median follow-up time of 39 months (range, 3-125 months). The median age was 36 years (range, 18-89 years); 61% were female; 76% were white; 45% had stage I disease, 60% had extranodal disease, and 55% were given RT. The 5-year OS for the entire cohort was 86%. On UVA, OS was improved with RT (hazard ratio [HR] 0.446, P=.029) and decreased in association with nonwhite race (HR 2.70, P=.006). The 5-year OS was 79% (no RT) and 90% (RT). On MVA, white race and RT remained significantly associated with improved OS (P=.007 and .018, respectively). The use of RT decreased over time: 61% for the 67 patients whose disease was diagnosed from 2001 to 2005 and 53% in the 138 patients treated from 2006 to 2010. CONCLUSION This retrospective population-based analysis is the largest PMBCL dataset to date and demonstrates a significant survival benefit associated with RT. Nearly half of patients treated in the United States do not receive RT, and its use appears to be declining. In the absence of phase 3 data, the use of RT should be strongly considered for its survival benefit in early-stage disease.

Treatment Selection and Survival Outcomes With and Without Radiation for Unresectable, Localized Intrahepatic Cholangiocarcinoma.

PurposeMost patients with intrahepatic cholangiocarcinoma present with locally advanced disease not amenable to surgical resection. For these inoperable patients, chemotherapy alone is generally considered the standard of care, with limited data regarding the role of radiotherapy. We used the National Cancer Database to investigate care patterns and the impact of radiation as a component of combined modality therapy on overall survival. MethodsWe queried the National Cancer Database for patients with nonmetastatic intrahepatic cholangiocarcinoma diagnosed from 2001 to 2011. Those undergoing surgery were excluded. All included patients were coded as having received chemotherapy. Kaplan-Meier overall survival estimates and univariate and multivariate Cox proportional hazards regression analyses were performed. Propensity score–matched analysis was performed to account for indication bias and mitigate heterogeneity between treatment groups. ResultsOne thousand six hundred thirty-six patients were identified with a median follow-up of 11.3 months. Median age was 63 years; 23% received combined modality therapy with radiation. Two-year overall survival for the entire cohort was 21%, and for the chemotherapy-alone and combined modality therapy groups, it was 20% versus 26%, respectively. On univariate analysis, overall survival was improved with combined modality therapy. On multivariate analysis, combined modality therapy remained significantly associated with improved overall survival, as did younger age, female sex, higher median income, lower comorbidity score, and earlier stage. Propensity score matched analysis confirmed the overall survival benefit associated with combined modality therapy. DiscussionIn this largest reported analysis of combined modality therapy for localized, inoperable intrahepatic cholangiocarcinoma, the addition of radiation to chemotherapy was associated with an improvement in overall survival. Three quarters of inoperable patients in the United States do not receive radiation. Survival remains relatively poor for all patients, and we enthusiastically support ongoing randomized trials seeking to incorporate radiotherapy as a possible means to improve outcomes.

The Impact of Postoperative Radiotherapy for Thymoma and Thymic Carcinoma

Introduction The optimal role for postoperative radiotherapy (PORT) for thymoma and thymic carcinoma remains controversial. We used the National Cancer Data Base to investigate the impact of PORT on overall survival (OS). Methods Patients who underwent an operation for thymoma or thymic carcinoma were categorized into Masaoka‐Koga stage groups I to IIA, IIB, III, and IV. Patients who did not undergo an operation or those who received preoperative radiation were excluded. Kaplan‐Meier estimates of OS and univariate and multivariate Cox proportional hazards regression analyses were performed. Propensity score–matched analyses were performed to further control for baseline confounders. Results From 2004 to 2012, 4056 patients were eligible for inclusion, 2001 of whom (49%) received PORT. On multivariate analysis of OS in the thymoma cohort adjusted for age, WHO histologic subtype, Masaoka‐Koga stage group, surgical margins, and chemotherapy administration, PORT was associated with superior OS (hazard ratio [HR] = 0.72, p = 0.001). Propensity score–matched analyses confirmed the survival advantage associated with PORT. Subset analysis indicated longer OS in association with PORT for patients with stage IIB thymoma (HR = 0.61, p = 0.035), stage III (HR = 0.69, p = 0.020), and positive margins (HR = 0.53, p < 0.001). The impact of PORT for stage I to IIA disease did not reach significance (HR = 0.76, p = 0.156). Conclusions In this large database analysis of PORT for thymic tumors, PORT was associated with longer OS, with the greatest relative benefits observed for stage IIB to III disease and positive margins. In the absence of randomized studies assessing the value of PORT, these data may inform clinical practice.

Survival outcomes of combined external beam radiotherapy and brachytherapy vs. brachytherapy alone for intermediate-risk prostate cancer patients using the National Cancer Data Base.

PURPOSE The purpose was to evaluate survival outcomes between external beam radiotherapy (EBRT) plus brachytherapy and brachytherapy alone for intermediate-risk prostate cancer, using the National Cancer Data Base. METHODS AND MATERIALS The National Cancer Data Base was queried for cN0M0 intermediate-risk patients treated from 2004 to 2006, with available data for Gleason score (GS), prostate-specific antigen (PSA), tumor stage, and receipt of radiation therapy (RT) and androgen deprivation therapy. RT comparison groups were the following: EBRT (40-50.4 Gy) plus brachytherapy and brachytherapy alone. RESULTS A total of 10,571 patients were included: 3,148 received EBRT plus brachytherapy and 7,423 received brachytherapy alone. Median followup was 84 months (2-122 months); median age was 68 years (40-90 years). Unadjusted 5- and 7-year overall survival (OS) rates between EBRT plus brachytherapy vs. brachytherapy alone were 91.4% vs. 90.2% and 85.7% vs. 82.9%, respectively (p < 0.001). EBRT plus brachytherapy was associated with longer OS compared with brachytherapy alone under multivariate (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.75-0.93; p = 0.001) and propensity score-matched analyses (HR, 0.85; 95% CI, 0.75-0.97; p = 0.006). Further subset analysis performed based on the Radiation Therapy Oncology Group 0232 inclusion criteria (GS 7 if PSA < 10 or GS < 7 if PSA 10-20) also demonstrated longer OS with EBRT plus brachytherapy (HR, 0.87; 95% CI, 0.77-0.98; p = 0.026). CONCLUSIONS EBRT plus brachytherapy is associated with a modest OS improvement compared with brachytherapy alone in this population-based analysis. Although this benefit appears statistically significant, the relatively small difference in OS raises the question of overall clinical benefit with combined modality RT for intermediate-risk prostate cancer, given the potential increased risk for toxicities. Future results from Radiation Therapy Oncology Group 0232 should provide further insight on this topic.

Assessing the use of 4DCT‐ventilation in pre‐operative surgical lung cancer evaluation

Purpose: A primary treatment option for lung cancer patients is surgical resection. Patients who have poor lung function prior to surgery are at increased risk of developing serious and life‐threatening complications after surgical resection. Surgeons use nuclear medicine ventilation‐perfusion (VQ) scans along with pulmonary function test (PFT) information to assess a patients pre‐surgical lung function. The nuclear medicine images and pre‐surgery PFTs are used to calculate percent predicted postoperative (%PPO) PFT values by estimating the amount of functioning lung tissue that would be lost with surgical resection. Nuclear medicine imaging is currently considered the standard of care when evaluating the amount of ventilation that would be lost due to surgery. A novel lung function imaging modality has been developed in radiation oncology that uses 4‐Dimensional computed tomography data to calculate ventilation maps (4DCT‐ventilation). Compared to nuclear medicine, 4DCT‐ventilation is cheaper, does not require a radioactive contrast agent, provides a faster imaging procedure, and has improved spatial resolution. In this work we perform a retrospective study to assess the use of 4DCT‐ventilation as a pre‐operative surgical lung function evaluation tool. Specifically, the purpose of our study was to compare %PPO PFT values calculated with 4DCT‐ventilation and %PPO PFT values calculated with nuclear medicine ventilation‐perfusion imaging. Methods: The study included 16 lung cancer patients that had undergone 4DCT imaging, nuclear medicine imaging, and had Forced Expiratory Volume in 1 second (FEV1) acquired as part of a standard PFT. The 4DCT datasets, spatial registration, and a density‐change‐based model were used to compute 4DCT‐ventilation maps. Both 4DCT‐ventilation and nuclear medicine images were used to calculate %PPO FEV1. The %PPO FEV1 was calculated by scaling the pre‐surgical FEV1 by (1‐fraction of total resected ventilation); where the resected ventilation was determined using either the 4DCT‐ventilation or nuclear medicine imaging. Calculations were done assuming both lobectomy and pneumonectomy resections. The %PPO FEV1 values were compared between the 4DCT‐ventilation‐based calculations and the nuclear medicine‐based calculations using correlation coefficients, average differences, and Receiver Operating Characteristic (ROC) analysis. Results: Overall the 4DCT‐ventilation derived %PPO FEV1 values agreed well with nuclear medicine‐derived %PPO FEV1 data with correlations of 0.99 and 0.81 for lobectomy and pneumonectomy, respectively. The average differences between the 4DCT‐ventilation and nuclear medicine‐based calculation for %PPO FEV1 were less than 5%. ROC analysis revealed predictive accuracy that ranged from 87.5% to 100% when assessing the ability of 4DCT‐ventilation to predict for nuclear medicine‐based %PPO FEV1 values. Conclusions: 4DCT‐ventilation is an innovative technology developed in radiation oncology that has great potential to translate to the surgical domain. The high correlation results when comparing 4DCT‐ventilation to the current standard of care provide a strong rationale for a prospective clinical trial assessing 4DCT‐ventilation in the clinical setting. 4DCT‐ventilation can reduce the cost and imaging time for patients while providing improved spatial accuracy and quantitative results for surgeons.

Patterns of Fractionation and Boost Usage in Adjuvant External Beam Radiotherapy for Ductal Carcinoma in Situ in the United States

Micro‐Abstract Among 101,615 American women with ductal carcinoma in situ diagnosed from 2004 through 2014, the use of hypofractionated radiotherapy after surgery increased, while that of boost decreased. However, conventional fractionation with a boost remained the most common strategy used. Both clinical factors, including age and pathologic features, and nonclinical factors, including income, facility type, and facility volume, were associated with these patterns. Background: While the roles of hypofractionated (HFxn) radiotherapy and lumpectomy boost in the adjuvant management of invasive breast cancer are supported by the results of clinical trials, randomized data supporting their use for ductal carcinoma in situ (DCIS) are forthcoming. We sought to evaluate current national trends and identify factors associated with HFxn and boost usage using the National Cancer Database. Patients and Methods: We queried the National Cancer Database for women diagnosed with DCIS from 2004 to 2014 undergoing external beam radiotherapy after breast conservation surgery. Patients were categorized as receiving either conventional fractionation (CFxn) or HFxn and as either receiving or not receiving a boost. Multiple logistic regression was performed to identify demographic, clinical, and treatment factor associations. Results: A total of 101,615 women were identified, with 87,641 (86.2%) receiving CFxn, 13,974 (13.8%) receiving HFxn, and most patients in each group (84.9% and 57.7%, respectively) receiving a boost. Implementation of HFxn increased from 4.3% in 2004 to 33.0% in 2014, and the use of a boost declined from 83.3% to 74.6%. HFxn receipt was independently associated with later year of diagnosis, older age, higher income, greater distance from treatment facility, greater facility volume, academic facility type, Western residence, smaller lesions, and nonreceipt of a boost. Factors associated with boost receipt included earlier year of diagnosis, younger age, higher income, community facility type, adverse pathologic features, and nonreceipt of HFxn. Conclusion: Although CFxn with a boost remains the most common external beam radiotherapy strategy for DCIS, implementation of HFxn without a boost appears to be increasing. Practice patterns at present seem to be driven by guidelines for invasive breast cancer and nonclinical factors.