Sean Szeja

Changes in Treatment Patterns and Overall Survival in Patients With Early-stage Non–small Cell Lung Cancer in the United States After the Incorporation of Stereotactic Ablative Radiation Therapy: A Population-based Analysis

Purpose: Technologic developments have made radiation therapy (RT) more effective and have introduced new treatment options, such as stereotactic ablative radiation therapy (SABR). This study sought to determine changes in practice patterns for treatment of stage IA non–small cell lung cancer (NSCLC) after the introduction of SABR into the United States. This population-based study also examined changes in survival during this time period for all patients and specifically for patients treated with RT, surgery, or observation. Methods: We included patients in the Surveillance, Epidemiology, and End Results database diagnosed with stage IA NSCLC diagnosed between 2004 and 2012. Changes in treatment patterns were assessed. Outcomes were compared across 2 time periods: 2004 to 2008 (pre-SABR) and 2009 to 2012 (post-SABR). Kaplan-Meier and Cox regression were performed to compare overall survival (OS) for patients treated with surgery, RT, or observation. Results: A total of 32,249 patients met the specified criteria. Comparing patients diagnosed in 2004 to those diagnosed in 2012, RT use increased from 13% to 29% (P<0.001), surgery use decreased from 76% to 61% (P<0.001), and patients observed decreased from 11% to 10% (P=0.3). There was no significant OS improvement in all patients or those patients who were observed; there were significant improvements in OS for patients treated with RT (hazard ratio=0.768; 95% confidence interval, 0.711-0.829) and those patients treated with surgery (hazard ratio=0.9; 95% confidence interval, 0.855-0.962). Conclusions: There has been an increase in RT utilization and decrease in surgical utilization after the incorporation of SABR by radiation oncologists within the United States. In addition, there has been an improvement in OS for patients treated with definitive RT for early-stage NSCLC between 2004 and 2012 that may be associated with increased utilization of SABR.

Practice Patterns and Outcomes in Elderly Stage I Non–Small-cell Lung Cancer: A 2004 to 2012 SEER Analysis

Micro‐Abstract We reviewed the population‐based outcomes for elderly patients with stage I non–small‐cell lung cancer (NSCLC) treated after the widespread adoption of stereotactic body radiation therapy (SBRT). Using the Surveillance, Epidemiology, and End Results database, biopsy‐proven stage I NSCLC cases diagnosed from 2004 to 2012 were identified (n = 62,213). With advancing age, radiation replaced surgery as the most used local therapy for early‐stage NSCLC. Concurrent with the widespread adoption of SBRT, overall and cancer‐specific survival improved significantly for elderly stage I NSCLC patients treated with SBRT alone. Background: We reviewed the population‐based treatment patterns and outcomes for elderly patients with stage I non–small‐cell lung cancer (NSCLC) treated from 2004 to 2012. Patients and Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified biopsy‐proven stage I NSCLC cases diagnosed from 2004 to 2012. The patients were divided into 5‐year age subsets (60‐64, 65‐69, 70‐74, 75‐79, 80‐84, 85‐89, and ≥ 90 years). The demographic data, therapy, and survival were compared by year. Trends in overall survival (OS), cancer‐specific survival (CSS), and practice patterns were analyzed. Results: A total of 62,213 cases were identified. The use of surgery declined sharply with age. Patients aged 60 to 64 years had a surgical rate of 81% compared with 21% for those aged ≥ 90 years (P < .0001). Radiation use increased (from 11% to 39%; P < .0001), as did the receipt of neither surgery nor radiation (from 7% to 40%; P < .0001). When analyzing the annual trends, radiation use increased, with fewer patients forgoing treatment from 2004 to 2012 (P < .0001). From 2004 to 2011, CSS at 2 years improved significantly for patients treated with radiation alone (from 48% to 72%; P < .0001) and more subtly for those receiving surgery alone (from 87% to 91%; P < .0001). The outcomes were stable for those receiving neither surgery nor radiation (38% to 45%; P = NS). Surgical outcomes declined with advancing age (P < .0001); however, the radiation outcomes did not (P = NS). Conclusion: With advancing age, radiation replaces surgery as the most used treatment for early‐stage NSCLC. OS and CSS have improved significantly for elderly stage I NSCLC patients treated with radiation alone during a timeline concurrent with the widespread adoption of stereotactic body radiation therapy. Dedicated prospective studies are indicated, because these findings are limited by the inherent biases of using the SEER database alone.

Outcomes associated with adjuvant radiation after lumpectomy for elderly women with T1-2N0M0 triple-negative breast cancer: SEER analysis.

39 Background: Adjuvant Radiation (RT) may be omitted for elderly women with early stage breast cancer having favorable estrogen receptor status, however in the setting of triple negative breast cancer (TNBC), less evidence exists to guide decision making. As some findings thus far have shown TNBC to have an increased recurrence rate, this is an important subject to address. The purpose of this study is to use the Surveillance, Epidemiology, and End Result (SEER) database to evaluate how the addition of adjuvant radiation affects the survival of women ages 70 and above with T1-2, N0, M0 TNBC that undergo Lumpectomy (L). METHODS Cases diagnosed from 2010-2011 were downloaded from the SEER Database. Inclusion criteria were ages 70 and above, with T1-2N0M0 TNBC. Kaplan meier curves calculated overall survival (OS) and disease specific survival (DSS) in months (m). Log-Rank tests were performed to compare survival. Cox multivariate regression was performed to calculate Hazard Ratios (HR) and control for confounding variables including neoadjuvant chemotherapy, number of lymph nodes sampled, age, laterality, grade, T stage, extent of surgery, existence of other cancers. RESULTS From 2010-2011, SEER contained 109,559 cases of breast cancer with recorded results of Her-2-neu (H2N) status. Combining other receptor values, showed 12,620 triple-negative, which was 12% of cases. Of these, 6980 (55%) had stage T1-2, N0, M0. Lumpectomy was used in 4002 of these cases. There were 974 lumpectomy cases of women aged 70 and above. RT was given in 662 (68%) cases. After 23 months, L+ RT was associated with improved OS at 98.2% compared to 85.6% for L only (p=<0.001), as well as DSS at 99% for L+RT better than 94% for L only (p=0.003). Cox Regression showed radiation demonstrated improved OS (HR=0.14, p<0.001) and DSS (0.14, p=0.01). CONCLUSIONS The use of adjuvant RT after lumpectomy for elderly women with early stage TNBC was associated with improved OS and DSS. Noting the potential for selection bias in this study, future prospective study is required to define the management of early stage triple negative breast cancer.

Treatment Outcomes and Prognostic Factors in Male Patients With Stage IV Breast Cancer: A Population-based Study

Micro‐Abstract Male breast cancer is a rare disease, and limited data exists regarding metastatic male breast cancer. To better characterize this population, we used the Surveillance, Epidemiology, and End Results database to examine prognostic factors that affected survival outcomes. On multivariate analysis, patients with progesterone receptor‐positive disease, younger age (≤ 65 years), tumor size ≤ 2 cm, or who had undergone surgery of the primary tumor had better overall survival and cause‐specific survival. Purpose: Male breast cancer (MBC) represents < 1% of breast cancer patients, and limited data exists regarding metastatic MBC. To better characterize this patient subset, we performed a population‐based study examining prognostic factors among patients with stage IV MBC. Methods: Patients with stage IV MBC diagnosed between 1988 and 2012 were selected from the Surveillance, Epidemiology, and End Results database. Prognostic factors for overall survival (OS) and cause‐specific survival (CSS) were evaluated. Results: Overall, 394 patients had metastatic disease meeting inclusion criteria. The median follow‐up was 21 months. The 5‐year OS and CSS rates were 21.1% and 38.3%, respectively. Of those with known progesterone receptor (PR) status, 52% were PR‐positive, which was associated with better OS (P < .001) and CSS (P = .003). Overall, 197 patients (50%) received surgery for the primary tumor, and 197 (50%) did not. Patients undergoing surgery had longer median CSS than those who did not (36 vs. 21 months; P < .001). Additional factors that correlated with prolonged OS and CSS were smaller tumor size (≤ 2 cm; P < .05) and younger age (≤ 65 years; P < .05). In multivariate analysis, smaller tumor size, PR‐positivity, younger age, and resection of the primary tumor were associated with longer OS and CSS (P < .05). Conclusions: Although stage IV MBC has poor OS and CSS, patients with PR‐positive disease, younger age (≤ 65 years), tumor size ≤ 2 cm, or who undergo surgery of the primary tumor have better OS and CSS. This is the largest study of stage IV MBC to date, and these findings address some of the questions regarding this rare presentation of breast cancer.

Changes in treatment patterns and impact of radiotherapy for early stage diffuse large B cell lymphoma after Rituximab: A population-based analysis

Purpose: Use of Rituximab for diffuse large B cell lymphoma (DLBCL) has improved outcomes and led to further questions regarding the benefit of consolidative radiation therapy (RT). This study sought to determine changes in RT utilization following the incorporation of Rituximab for treatment of early stage DLBCL and to examine survival outcomes. Materials/methods: We included patients in the Surveillance, Epidemiology, and End Results database, diagnosed with Stage I–II DLBCL between 1992 and 2011. Linear regression was performed to determine rate of RT utilization over time during the preand post-Rituximab eras (1992–2001 vs. 2002–2011). Kaplan–Meier and Cox Regression were performed to compare overall survival (OS) for patients treated with or without RT. Propensity-score matching was used to compare survival outcomes to account for indication bias. Results: 34,680 patients met the specified criteria. RT utilization was 35.2% in the pre-Rituximab era and 29.9% in the post-Rituximab era (P < 0.001). Linear regression revealed that in the pre-Rituximab era the slope of the best fit line for RT utilization by year was positive (m = 0.01, P = 0.0046), while the slope was negative in the post-Rituximab era (m = 0.008, P = 0.0102). RT use was associated with improved OS in both the pre-Rituximab era (hazard ratio [HR] = 0.797; 95% confidence interval [CI] 0.756–0.841) and the post-Rituximab era (HR = 0.745; 95% CI 0.702–0.789). Propensity-score matched analysis confirmed that RT use improved OS in the pre-Rituximab era (HR = 0.844; 95% CI 0.793–0.897) and post-Rituximab era (0.754; 95% CI 0.703–0.809). Conclusion: RT utilization has decreased following incorporation of Rituximab for first line treatment of DLBCL. RT use is associated with improved OS in both preand post-Rituximab eras, suggesting that RT should continue to be used for management of early stage DLBCL, even in the era of Rituximab. 2016 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology xxx (2016) xxx–xxx Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin’s lymphoma in the United States, accounting for 25–35% of all adult non-Hodgkin’s lymphomas [1–2]. Treatment for early stage DLBCL is controversial with the National Comprehensive Cancer Network (NCCN) guidelines recommending chemotherapy with or without radiation therapy (RT) [3]. In the pre-Rituximab era, four randomized trials failed to demonstrate a survival benefit with the addition of RT to chemotherapy, though the Southwestern Oncology Group Study 8736 did demonstrate improved overall survival with the addition of RT at the initial publication after a median follow up time of 4.4 years, which failed to persist after longer follow up [4–8]. Rituximab is a chimeric anti-CD20 IgG1 monoclonal antibody that was demonstrated to have efficacy in management of relapsed or refractory DLBCL in 1998 [9]. In 2002, the Groupe D’Etude des Lymphomes de l’Adulte (GELA) first demonstrated dramatic improvements in overall survival (OS), event-free survival, and disease-free survival with the addition of Rituximab to CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) compared to CHOP alone for first line treatment of DLBCL [10,11]. Multiple retrospective analyses in the Rituximab era have demonstrated improved outcomes with the addition of consolidative RT after Rituximab based chemotherapy [12–18]. Subset

Management of the primary site in stage IV non-small cell lung cancer: SEER analysis.

52 Background: One of every three non-small cell lung cancer (NSCLC) patients is diagnosed with terminal stage IV disease. As systemic treatments have evolved, other tumor sites such as kidney have demonstrated benefits of aggressive management of the primary location and oligo-metastases. The purpose of this study is to use the SEER database to evaluate survival outcomes associated with surgery (S) and radiation treatment (RT) of the primary site in stage IV NSCLC. METHODS Eligible patient cases had lung coded as the primary location. The analysis was limited to histology of squamous cell carcinoma or adenocarcinoma, M1 staging, had recorded extent of surgery and status of radiation, were taken from years 1998-2013 and grouped from 1998-00, 01-05, 06-10, 11-2013 for temporal analysis. Kaplan-Meier was used to estimate median overall survival (MOS) and lung cancer specific survival (CSS). RESULTS There were 41150 patients meeting inclusion criteria with median follow up of 4 months limited by survival. Treatment was S only to 494, RT only to 20346, S+RT to 731 and neither to 19579. Of the dual modality patients, 85 had RT before S, 525 after and 121 unknown order. Node negative surgical patients undergoing lobectomy had better median OS & CSS (30 & 35 m respectively) than all other surgical categories (eg. wedge resection with 13 & 17m, pneumonectomy with 10 & 15m). Median OS & CSS decreased slightly from 5 to 3 and 6 to 4 months over the time from 2000-2013. In the subset with N0 disease, those receiving both S+RT observed an increase of median OS & SS from 11 to greater than 35 months (median not reached in 2013) while no trend was seen for other treatment strategies, which were ~5 months in 2013. CONCLUSIONS Potential sources of confounding and bias must be regarding when interpreting our findings. These include selection of patient for aggressive treatment, both local and systemic, the latter of which this database does not describe. Our findings demonstrate that, in stage IV NSCLC, aggressive management of the primary site with surgery and radiation in patients with limited local disease such as N0 lymph nodes is associated with prolonged survival.

Simultaneous Integrated Boost using Conformal Radiation Therapy for Treatment of Cervical Cancer

Purpose: Chemoradiation is the treatment of choice for locally advanced cervical cancer. At our institution, we have been using forward planned conformal radiation therapy to treat patients to the whole pelvis with asimultaneous integrated boost (SIB) to the uterus and parametria. Our aim is to report the local control, disease free survival, overall survival, and toxicities of definitive chemoradiation with SIB for treatment of cervical cancer. Methods: Medical records and treatment plans of patients with cervical cancer treated from 2009-2013 were reviewed using an IRB-approved database. The records of patients with cervical cancer treated with definitive chemoradiation and a three dimensional forward planned SIB were analyzed to determine local failure, distant failure, overall survival, and rate of toxicities. Results: Twenty one patients were treated with definitive chemoradiation with a SIB. Median follow up time was 18.1 months. The 2-year LC rate was 95.2%, the 2-year DFS was 80.9%, and there were no deaths, for an overall survival rate of 100%. One patient experienced Grade 3 or higher acute toxicity, and two patients experienced Grade 3 or higher late toxicities. Conclusions: This study demonstrates the feasibility and tolerability of SIB using forward planned conformal radiation therapy for the treatment of cervical cancer. This radiation technique can be used to deliver a higher dose to the area most at risk for recurrence in a shorter treatment time *Corresponding Author: Waqar Haque, MD, Deparment of Radiation Oncology, Greater Houston Physicians in Medicine, Association Houston, TX 77030, Tel: 832-367-1655/ Fax: 832-201-0602; E-mail: WAQARH786@gmail.com Received Date: February 02, 2016 Accepted Date: April 21, 2016 Published Date: April 27, 2016