Image-guided tandem and cylinder brachytherapy as monotherapy for definitive treatment of inoperable endometrial carcinoma.

OBJECTIVES: Management of endometrial cancer consists of surgical staging with adjuvant therapy guided by risk factors, though some women cannot undergo surgery due to comorbidities. We present a series of women treated with definitive high-dose rate image-guided tandem and cylinder brachytherapy (HDR-IGBT) alone. METHODS: Patients with grade 1-2, clinical stage I endometrial adenocarcinoma, <50% myometrial invasion, and tumor≤2cm were reviewed. Definitive treatment consisted of 5-6 fractions HDR-IGBT alone with CT- or MRI-based planning. Local-regional control (LRC) was defined as complete imaging response and/or cessation of vaginal bleeding. RESULTS: From 2007 to 2016, 45 patients were treated to a median dose of 37.5Gy. The median gross tumor volume (GTV) and clinical target volume (CTV) were 5.9cm3 (range, 0.7-18.7) and 80.9cm3 (17.2-159.0), respectively. The median cumulative dose to 90% (D90) of the GTV was 132.8Gy (76.5-295.6) equivalent 2Gy dose, and the median CTV D90 was 49.7Gy (34.5-57.2). Median follow-up among living patients was 18.6months (3.0-64.3). Cessation of vaginal bleeding occurred in 98%. Among those with post-treatment MRI (64%), complete radiographic response was demonstrated in 90%. The 2-year LRC, cancer-specific survival, and overall survival rates were 90%, 86%, and 97%, respectively. No grade 3+ acute or late toxicity was observed. CONCLUSIONS: HDR-IGBT alone for treatment of early-stage, medically inoperable endometrial cancer is feasible with excellent response rates and clinical results. This approach also allows sparing of critical organs and ensures target coverage, which contributed to the low toxicity rate and high LRC in comparison with 2D point-based series.

Outcomes of stage II endometrial cancer: The UPMC Hillman Cancer Center experience.

PURPOSE: Previous studies of stage II endometrial cancer have included cancers with cervical glandular involvement, a factor no longer associated with risk of recurrence. In order to better assess relapse patterns and the impact of adjuvant therapy, a retrospective analysis was conducted for patients with modern stage II endometrial cancer, defined as cervical stromal invasion. MATERIALS AND METHODS: Patients diagnosed with surgically staged FIGO stage II endometrial cancer at the UPMC Hillman Cancer Center from 1990-2013 were reviewed. Factors associated with rates of locoregional control (LRC), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS) were analyzed using the log rank test. RESULTS: 110 patients with FIGO stage II disease were identified. Most (84.5%) received EBRT±BT, with 13.6% receiving BT alone. With a median follow-up of 64.6months, the 5-year actuarial rates of LRC, DM, DFS, and OS were 94.9%, 85.1%, 67.9%, and 75.0%, respectively. With 5 locoregional failures, the only factor predictive of LRC was pelvic lymph node dissection. Characteristics associated with DM included age, LVSI, depth of myometrial invasion, and receipt of chemotherapy. Factors predictive of both DFS and OS were age, grade, adverse histology, LVSI, depth of myometrial invasion, and receipt of chemotherapy. CONCLUSIONS: This represents the largest single-institution study for modern stage II endometrial cancer, confirming high rates of pelvic disease control after surgery and adjuvant therapy. With most patients receiving adjuvant radiotherapy, the predominant mode of failure, albeit low in absolute number, remains distant metastases.

Salvage stereotactic radiosurgery for recurrent gliomas with prior radiation therapy.

This study aims to assess the viability of salvage stereotactic radiosurgery (SRS) for recurrent malignant gliomas through assessing overall survival, local control and toxicity. We performed a retrospective review of 65 patients with 76 lesions (55 high-grade, 21 low-grade) treated with salvage SRS between 2002 and   2012. Median follow-up from salvage SRS was 14.9 months (IQR: 0.9-28.1), 8.3 months (IQR: 4.0-13.3) and 8.5 months (IQR: 3.9-15.8) for low-grade, high-grade, and combined, respectively. A 12-month overall survival from salvage SRS was 68.4, 38.7 and 47.3% for low-grade, high-grade and combined respectively. A total of 6-month local control was 86.2, 53.8 and 65.3% for low-grade, high-grade and combined, respectively. Our results indicate salvage SRS can provide acceptable survival and local control with minimal toxicity.

Utilization and Role of Adjuvant Radiotherapy and Chemotherapy for Uterine Clear Cell Carcinoma: A National Cancer Data Base Analysis.

OBJECTIVE: Because of the rarity of uterine clear cell carcinoma (UCCC), a National Cancer Data Base analysis was conducted to evaluate practice patterns and implications of adjuvant therapy. METHODS: The National Cancer Data Base was queried for UCCC patients diagnosed from 1998 to 2011. Patients receiving neoadjuvant therapy, lacking surgical staging, or having follow-up time shorter than 6 months were excluded. Factors associated with utilization were assessed using logistic regression. To define the probability of receiving chemotherapy and radiotherapy (CT + RT), propensity scores with inverse probability of treatment weighting (IPTW) were calculated using multivariable logistic regression. Log-rank test and multivariable IPTW-adjusted Cox proportional hazards modeling were then conducted. RESULTS: A total of 2504 patients were identified, with a median follow-up of 65.5 months. Most patients had FIGO (International Federation of Gynecology and Obstetrics) stage I to II UCCC (71.4%). Adjuvant RT alone, CT alone, or CT + RT was given in 35.3%, 9.5%, and 11.7%, respectively. Among those receiving RT, external beam was the most common modality (69.4%). Later year of diagnosis (>2005: odds ratio [OR], 4.42; 95% confidence interval [95% CI], 2.44-8.01), higher FIGO stage (IIIA-IIIC2: OR, 6.34; 95% CI, 3.93-10.24), larger tumor size (3.6-5.0 cm: OR, 3.40; 95% CI, 1.76-6.55), and lymph node dissection (OR, 4.22; 95% CI, 1.60-11.15) were associated with a higher chance of receiving CT + RT. With IPTW-adjusted multivariable analysis, CT + RT significantly decreased mortality risk in stage III to IVA patients (hazards ratio, 0.41; 95% CI, 0.22-0.77), trending toward benefit in stage I to II patients (hazards ratio, 0.53; 95% CI, 0.27-1.07). CONCLUSIONS: In this hospital-based registry analysis of UCCC, adjuvant CT + RT significantly reduced the risk of death, reaching statistical significance for stage III to IVA patients.

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

BACKGROUND: 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. METHODS: A National Cancer Data Base retrospective cohort study was conducted of 35,961 patients with lymph node and extranodal, American Joint Committee on Cancer stage I to II, WHO grade 1 to 2 follicular lymphoma who were diagnosed between 1998 and 2012. Univariate and multivariable analyses were performed to identify sociodemographic, treatment, and tumor characteristics that were predictive of overall survival (OS) and treatment use. Propensity score-adjusted Cox proportional hazards ratios for survival in patients treated for follicular lymphoma were used. RESULTS: Of the 35,961 patients with follicular lymphoma included in the current study, 63% had stage I disease, 79% were without extranodal disease, and 61% were aged >60 years. RT use decreased from 37% in 1999 to 24% in 2012 (P<.0001), with corresponding significant increases in observation and single-agent chemotherapy. Patients who received RT had 5-year and 10-year OS rates of 86% and 68%, respectively, compared with 74% and 54%, respectively, for those who did not receive RT (P<.0001). On multivariable survival analysis, including a propensity score to account for potential uncaptured confounding variables due to a lack of randomization, upfront RT remained independently associated with improved OS (hazard ratio of death, 0.54; 95% confidence interval, 0.47-0.63 [P<.0001]). CONCLUSIONS: RT is an increasingly underused treatment approach in the era of modern therapy for patients with early-stage follicular lymphoma. The use of RT appears to improve OS and should remain standard practice as encouraged by clinical practice guidelines.

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.

Patterns of care and outcomes for adjuvant treatment of pT3N0 rectal cancer using the National Cancer Database.

BACKGROUND: The standard of care in locally advanced rectal cancer is preoperative chemoradiation followed by surgical resection. However, the optimal treatment paradigm is currently controversial for patients with pathological T3N0 (pT3N0) in the era of total mesorectal excision (TME). Given the paucity of data, we conducted an analysis using the National Cancer Database (NCDB) to identify patterns of care and outcomes. METHODS: We utilized the NCDB to identify 7,836 non-metastatic, pT3N0 rectal cancer patients who did not receive neoadjuvant therapy from 2004-2014. Univariate and multivariable analysis for factors affecting treatment selection were completed using logistic regression. Overall survival (OS) analyses were completed using Cox regression modeling, incorporating propensity scores with inverse probability of treatment weighting (IPTW) and conditional landmark analysis. RESULTS: There was a significant improvement in OS in patients receiving adjuvant chemotherapy (P<0.01) or radiotherapy (RT) with chemotherapy (P<0.01) vs. observation alone. There was no significant difference between RT vs. observation (P=0.54) and chemotherapy vs. chemotherapy with RT cohorts (P=0.15). Multivariable analysis showed age, gender, race, insurance status, income, Charlson-Deyo Comorbidity Condition (CDCC) score, facility location, grade, surgical margin, RT, and chemotherapy to be statistically significant predictors of OS. After correcting for indication and immortal time biases, chemotherapy, with or without RT, improved OS compared with observation [hazard ratio (HR) 0.48, P<0.001]. This benefit was maintained in the margin negative cohort. CONCLUSIONS: Practice patterns vary in the management of pT3N0 rectal cancer patients. This analysis suggests that the use of adjuvant therapy, particularly adjuvant chemotherapy with or without RT, appears to improve OS.

The Impact of Serum Glucose in the Treatment of Locoregionally Advanced Pancreatic Cancer.

INTRODUCTION: Studies have consistently identified an increased risk of pancreatic cancer in diabetics, yet the role hyperglycemia may play in predicting prognosis is less clear. This work aims to evaluate the impact of glycemic state and antidiabetics on outcomes after systemic and local treatment for locoregionally advanced pancreatic cancer. MATERIALS AND METHODS: This retrospective study consisted of 303 patients with newly diagnosed advanced-stage pancreatic cancer treated from 2004 to 2014. Kaplan-Meier survival analysis method was used to estimate time to event for overall survival, distant metastasis, and locoregional control. Blood glucose values (n=8599) were assessed both as continuous and categorical variables in univariate and multivariable Cox proportional hazard regression models to estimate hazard ratios (HRs) and identify independent prognostic factors. A 6-month conditional landmark analysis excluding patients with <6 months follow-up or survival was conducted. RESULTS: Median follow-up and survival was 18.1 and 18.4 months, respectively. On univariate analysis, maximum pretreatment glucose value was associated with reduced overall survival (HR 1.005, P=0.023) and locoregional control (HR 1.001, P=0.001). A pretreatment glucose value ≥200 mg/dL was associated with increased mortality in multivariable analysis (adjusted HR 1.01, P=0.015). After conditional analysis, glucose ≥200 mg/dL before local treatment was associated with reduced overall survival (adjusted HR 1.562; 95% confidence interval [CI], 1.16-2.11; P=0.003). CONCLUSIONS: Elevated blood glucose before treatment of locoregionally advanced pancreatic cancer was associated with poorer outcomes. These findings should be incorporated in future clinical trial design.

Early Exploratory Analysis for Patient-reported Quality of Life and Dosimetric Correlates in Hypofractionated Stereotactic Body Radiation Therapy (SBRT) for Low-risk and Intermediate-risk Prostate Cancer: Interim Results from a Prospective Phase II Clinical Trial.

OBJECTIVES: Given the relative novelty of stereotactic body radiation therapy as a treatment modality low-risk and intermediate-risk prostate cancer, little data exist evaluating dosimetry and its impact on patient-reported quality of life (PR-QOL) metrics. Herein, we present an interim analysis of a phase II clinical trial of PR-QOL and dosimetric correlates. METHODS: Patients with biopsy-proven low-risk or intermediate-risk prostate cancer, prostate volume ≤100 cm, and life expectancy ≥10 years were enrolled. Expanded Prostate Cancer Index Composite (EPIC) scores were tabulated by domain and evaluated in relation to dosimetry. Paired t test was performed to compare differences in scores from baseline. Minimally important differences were established using the anchor-based approach and correlations made using the χ test. RESULTS: A total of 95 patients were analyzed with a median follow-up of 18.1 months (range, 3.0 to 76.9 mo). There were no cases of acute or late grade 3+ GI or GU toxicities. Expanded Prostate Cancer Index Composite scores in urinary obstructive/irritative domain at 1 month (-4.8, P=0.03) and bowel domain at 1, 6, and 12 months (-10.8, -6.1, and -5.2) were significantly different from pretreatment, with both returning to nonsignificant differences around 24 months. Higher bladder V37Gy (≥3.35%) was associated with both late urinary incontinence and obstructive/irritative declines. Both higher rectal D5% and rectal V36Gy >0.6 cm were correlated with an enhanced proportion of patients with late minimally important difference declines. CONCLUSIONS: Higher dose volumes for the bladder and rectum predicted for poorer PR-QOL. In contrast to prostate brachytherapy data, neither prostate volume nor urethral dosimetry at this dose schedule correlated with urinary symptoms.

The Impact of Serum Glucose, Anti-Diabetic Agents, and Statin Usage in Non-small Cell Lung Cancer Patients Treated With Definitive Chemoradiation.

Introduction: Epidemiologic data indicate diabetes confers an augmented risk of lung cancer development, yet the relationship between hyperglycemia, metabolic agents, and prognosis is unclear. We analyzed the impact of hyperglycemia, anti-diabetic agents, and statins on outcomes in non-small cell lung cancer (NSCLC) patients undergoing chemoradiation. Method and Materials: In total, data from 170 patients with stage III NSCLC treated at the University of Pittsburgh Medical Center between 2001 and 2014 were obtained for analysis. Kaplan-Meier survival analysis was used to estimate time-to-event for overall survival (OS), disease-free survival, distant metastasis (DM), and loco-regional control (LRC). Blood glucose values (n = 2870), statins, and diabetic medications were assessed both continuously and categorically in univariable and multivariable Cox proportional hazard regression models to estimate hazard ratios and identify prognostic factors. Results: Tumor volume was a negative prognostic factor for OS, disease-free survival, DM, and LRC (p = 0.001). Tumor stage and treatment time were associated with increased all-cause mortality. Any glucose measurement ≥ 130 mg/dl during treatment (2-year estimate 49.9 vs. 65.8%, p = 0.095) was borderline significant for decreased LRC, with similar trends on multivariable analysis (HR 1.636, p = 0.126) and for OS (HR 1.476, p = 0.130). Statin usage was associated with improved 2-year LRC (53.4 vs. 62.4%, p = 0.088) but not with improvements in survival. Other glycemic parameters, comorbid diabetes diagnosis, or anti-diabetic medications were not significantly associated with outcomes. Conclusions: There were trends for blood glucose value over 130 mg/dl and statin nonuse being associated with inferior prognosis for LRC in stage III NSCLC patients; glycemic state, statin usage, and glucose-modulating medications were not associated with survival outcomes in multivariable analysis in this retrospective database.

Targeting Tumor Metabolism With Statins During Treatment for Advanced-stage Pancreatic Cancer.

INTRODUCTION: A growing body of preclinical data suggests that statins may exert potent antitumor effects, yet the interactions of these medications with standard therapies and clinical outcomes in this population is less clear. We assessed the impact of statin use on outcomes in patients with advanced-stage pancreatic adenocarcinoma undergoing various treatments. MATERIALS AND METHODS: After institutional review board approval, we conducted a retrospective-cohort study consisting of 303 newly diagnosed advanced-stage pancreatic adenocarcinoma patients to determine the impact of statin use on outcomes. Univariate and multivariable Cox proportional hazard regression models were utilized to estimate hazard ratios (HRs). Time-to-event was estimated using Kaplan-Meier survival analysis for overall survival, distant metastasis, and locoregional failure. Baseline and active statin usage were assessed and to mitigate risk of immortal time bias, subanalysis excluding patients with under 6 months of follow-up was conducted. RESULTS: Both prior (P=0.021) and active (P=0.030) statin usage correlated with improved survival in this cohort. Surgery, chemoradiation, and statin use improved 2-year survival rates (84.1% vs. 55.0%; P<0.001). On multivariable analysis, statin exposure was associated with overall survival (HR, 0.662; P=0.027) and trended to significance for freedom from distant metastasis (HR, 0.577; P=0.060). Comorbid conditions were not significantly associated with outcomes. CONCLUSIONS: Statin use was associated with improved overall survival in advanced-stage pancreatic adenocarcinoma patients. This data supports previous findings in early-stage pancreatic adenocarcinoma and other cancer sites. To our knowledge this is the first report to examine the efficacy of statin use as a supplementary treatment option in advanced-stage pancreatic adenocarcinoma patients.

Adjuvant Radiation Therapy for Margin-Positive Vulvar Squamous Cell Carcinoma: Defining the Ideal Dose-Response Using the National Cancer Data Base.

PURPOSE: Positive surgical margins after radical vulvectomy for vulvar cancer portend a high risk for local relapse, which may be challenging to salvage. We assessed the impact of adjuvant radiation therapy (aRT) on overall survival (OS) and the dose-response relationship using the National Cancer Data Base. METHODS AND MATERIALS: Patients with vulvar squamous cell carcinoma who underwent initial extirpative surgery with positive margins from 1998 to 2012 were included. Factors associated with aRT and specific dose levels were analyzed using logistic regression. Log-rank and multivariable Cox proportional hazards modeling were used for OS analysis. RESULTS: We identified 3075 patients with a median age of 66 years (range, 22-90 years); the median follow-up time was 36.4 months (interquartile range [IQR] 15.4-71.0 months). Stage IA/B disease represented 41.2% of the cohort. Sixty-three percent underwent lymph node assessment, with a 45% positivity rate. In total, 1035 patients (35.3%) received aRT, with a median dose of 54.0 Gy (IQR 48.6-60.0 Gy). The 3-year OS improved from 58.5% to 67.4% with aRT (P<.001). On multivariable analysis, age, Charlson-Deyo score ≥1, stage ≥II, tumors ≥4 cm, no aRT, and adverse nodal characteristics led to inferior survival. Dose of aRT was positively associated with OS as a continuous variable on univariate analysis (P<.001). The unadjusted 3-year OS for dose subsets 30.0 to 45.0 Gy, 45.1 to 53.9 Gy, 54.0 to 59.9 Gy, and ≥60 Gy was 54.3%, 55.7%, 70.1%, and 65.3%, respectively (P<.001). Multivariable analysis using a 4-month conditional landmark revealed that the greatest mortality reduction occurred in cumulative doses ≥54 Gy: 45.1 to 53.9 Gy (hazard ratio [HR] 0.94, P=.373), 54.0 to 59.9 Gy (HR 0.75, P=.024), ≥60 Gy (HR 0.71, P=.015). No survival benefit was seen with ≥60 Gy compared with 54.0 to 59.9 Gy (HR 0.95, P=.779). CONCLUSIONS: Patients with vulvar squamous cell carcinoma and positive surgical margins derive an OS benefit from aRT with a seemingly optimal dose in the range of 54.0 to 59.9 Gy.

Long-term outcomes using adjuvant pelvic intensity modulated radiation therapy (IMRT) for endometrial carcinoma.

PURPOSE: We evaluated the long-term outcome and toxicity of adjuvant intensity modulated radiation therapy (IMRT) for high-risk endometrial carcinoma via a retrospective institutional review of patients treated in this setting with extended follow-up. METHODS AND MATERIALS: Patients with endometrial cancer who underwent comprehensive surgical staging followed by adjuvant IMRT with or without sequential chemotherapy between 1999 and 2010 were reviewed. Median doses delivered with IMRT and brachytherapy were 45 Gy in 25 fractions and 10 Gy in 2 fractions; 10.2% received extended field and 94.5% received vaginal brachytherapy. Kaplan-Meier estimates are provided for rates of locoregional (in-field) relapse, distant metastasis, and disease-free survival, and overall survival. Gastrointestinal (GI) and genitourinary (GU) toxicity reported were graded with the Common Terminology Criteria for Adverse Events, version 4.03. RESULTS: A total of 128 patients were identified. Median age at diagnosis was 64 years. Most patients (82.8%) had endometrioid adenocarcinoma followed by papillary serous (10.2%), clear cell (4.7%), and carcinosarcoma (2.3%). International Federation of Gynecology and Obstetrics staging distribution was as follows: IA, 13.3%; IB, 32.8%; II, 30.4%; IIIA, 5.5%; IIIC1, 9.4%; and IIIC2, 8.6%. Most (85.9%) underwent nodal dissections (28.1% pelvic only and 57.8% pelvic and para-aortic). Two patients (1.6%) experienced acute grade 3 GI toxicity; no other acute grade ≥3 GI/GU toxicities were noted. With a median follow-up of 57.0 months, 5-year locoregional relapse was 2.5%: vagina (n = 3), parametrium (n = 1), pelvic node (n = 1). Five-year estimates of distant metastasis, disease-free survival, and overall survival were 16.5%, 73.4%, and 77.4%, respectively. Five-year actuarial rates of late grade 3 GI and GU toxicities were 3.2% and 0.0%. The 5-year rate of symptomatic pelvic insufficiency fracture was 4.4%. CONCLUSIONS: This study represents the largest cohort of endometrial cancer patients with extended follow-up receiving adjuvant IMRT. High rates of pelvic disease control and limited late toxicities demonstrate safety and efficacy of this approach in the setting of extended follow-up.

One- vs. Three-Fraction Pancreatic Stereotactic Body Radiation Therapy for Pancreatic Carcinoma: Single Institution Retrospective Review.

BACKGROUND/INTRODUCTION: Early reports of stereotactic body radiation therapy (SBRT) for pancreatic ductal adenocarcinoma (PDAC) used single fraction, but eventually shifted to multifraction regimens. We conducted a single institution review of our patients treated with single- or multifraction SBRT to determine whether any outcome differences existed. METHODS AND MATERIALS: Patients treated with SBRT in any setting for PDAC at our facility were included, from 2004 to 2014. Overall survival (OS), local control (LC), regional control (RC), distant metastasis (DM), and late grade 3 or greater radiation toxicities from the time of SBRT were calculated using Kaplan-Meier estimation to either the date of last follow-up/death or local/regional/distant failure. RESULTS: We identified 289 patients (291 lesions) with pathologically confirmed PDAC. Median age was 69 (range, 33-90) years. Median gross tumor volume was 12.3 (8.6-21.3) cm3 and planning target volume 17.9 (12-27) cm3. Single fraction was used in 90 (30.9%) and multifraction in 201 (69.1%) lesions. At a median follow-up of 17.3 months (IQR 10.1-29.3 months), the median survival for the entire cohort 17.8 months with a 2-year OS of 35.3%. Univariate analysis showed multifraction schemes to have a higher 2-year OS 30.5% vs. 37.5% (p = 0.019), it did not hold significance on MVA. Multifractionation schemes were found to have a higher LC on MVA (HR = 0.53, 95% CI, 0.33-0.85, p = 0.009). At 2 years, late grade 3+ toxicity was 2.5%. Post-SBRT CA19-9 was found on MVA to be a prognostic factor for OS (HR = 1.01, 95% CI, 1.01-1.01, p = 0.009), RC (HR = 1.01, 95% CI 1.01-1.01, p = 0.02), and DM (HR = 1.01, 95% CI, 1.01-1.01, p = 0.001). CONCLUSION: Our single institution retrospective review is the largest to date comparing single and multifraction SBRT and the first to show multifraction regimen SBRT to have a higher LC than single fractionation. Additionally, we show low rates of severe late toxicity with SBRT.

Results of a Single Institution Experience with Dose-Escalated Chemoradiation for Locally Advanced Unresectable Non-Small Cell Lung Cancer.

BACKGROUND: We determined factors associated with morbidity and outcomes of a series of non-small cell lung cancer (NSCLC) patients treated with dose-escalated chemoradiotherapy at the University of Pittsburgh Lung Cancer Program. METHODS AND MATERIALS: The records of 170 stage III NSCLC patients treated with definitive intent were retrospectively reviewed. All patients received four-dimensional CT simulation scan and had respiratory gating if tumor movement exceeded 5 mm. Overall survival (OS), locoregional control (LRC), and freedom from distant metastasis (FFDM) were calculated using log-rank and Cox regression analysis. RESULTS: For the present series of patients, median follow-up was 36.6 months, median survival 27.4 months, and the 2- and 4-year OS was 56.0 and 30.7%, respectively. The 4-year LRC and FFDM were 43.9 and 40.7%, respectively. No benefit was associated with irradiation doses above 66 Gy in OS (p = 0.586), LRC (p = 0.440), or FFDM (p = 0.230). On univariate analysis, variables associated with worse survival included: clinical stage IIIB (p = 0.037), planning target volume (PTV) over 450 cc (p < 0.001), heart V30 over 40% (p = -0.048), and esophageal mean dose over 20% (p = 0.024), V5 (p = -0.015), and V60 (p = -0.011). On multivariable analysis, PTV above 450 cc (52.2 vs. 25.3 months, p < 0.001) and esophageal V60 >20% (43.8 vs. 21.3 months, p = -0.01) were associated with lower survival. Grade 2 or higher acute lung toxicity and esophagitis were detected in 9.5 and 59.7%, respectively of patients. Grade 2 or higher acute lung toxicity was reduced if lung V5 was ≤65 (7.4 vs. 23.8%, p = 0.03). Grade 2 or higher acute esophagitis was reduced if V60 ≤ 20% (62 vs. 81.3%, p = 0.018). The use of intensity-modulated radiation therapy was more frequent in stage IIIB compared to stage IIIA patients (56.5 vs. 39.5%, p = 0.048) and was associated with a higher lung V5 and V10. CONCLUSION: The outcomes of a program of dose-escalated chemoradiotherapy for unresectable stage IIIA and IIIB NSCLC patients were consistent with other studies and showed no benefit to radiation doses above 66 Gy. Furthermore, maintaining low esophageal V60 and lung V5 were associated with lower morbidity and mortality.

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

BACKGROUND: Anaplastic thyroid cancer (ATC) represents a rare, aggressive malignancy. We analyzed factors predictive for overall survival (OS) and treatment modality utilization. METHODS: Using the National Cancer Data Base, we identified 3552 patients with ATC. Factors associated with surgery, high-dose radiotherapy (RT; ≥59.4 Gy), and chemotherapy utilization were evaluated using multivariable logistic regression. From this, an inverse probability-weighted propensity score was incorporated into multivariable Cox regression analyses for OS. RESULTS: Numerous factors predictive for high-dose RT, total thyroidectomy, and chemotherapy utilization are described. Factors associated with improved survival were absence of clinical or pathologic lymph node involvement, absence of metastasis, tumor size ≤6 cm, negative surgical margins, surgery, RT, and chemotherapy. On conditional landmark analysis, improved survival seen with chemotherapy and surgery other than total thyroidectomy was lost, but persisted for total thyroidectomy and high-dose RT. CONCLUSION: Even after correction for selection and immortal time bias, high-dose RT resulted in improved survival. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2083-E2090, 2016.

Cost-Effectiveness Analysis of Stereotactic Body Radiation Therapy Compared With Radiofrequency Ablation for Inoperable Colorectal Liver Metastases.

PURPOSE: To conduct a cost-effectiveness analysis to determine whether stereotactic body radiation therapy (SBRT) is a cost-effective therapy compared with radiofrequency ablation (RFA) for patients with unresectable colorectal cancer (CRC) liver metastases. METHODS AND MATERIALS: A cost-effectiveness analysis was conducted using a Markov model and 1-month cycle over a lifetime horizon. Transition probabilities, quality of life utilities, and costs associated with SBRT and RFA were captured in the model on the basis of a comprehensive literature review and Medicare reimbursements in 2014. Strategies were compared using the incremental cost-effectiveness ratio, with effectiveness measured in quality-adjusted life years (QALYs). To account for model uncertainty, 1-way and probabilistic sensitivity analyses were performed. Strategies were evaluated with a willingness-to-pay threshold of $100,000 per QALY gained. RESULTS: In base case analysis, treatment costs for 3 fractions of SBRT and 1 RFA procedure were $13,000 and $4397, respectively. Median survival was assumed the same for both strategies (25 months). The SBRT costs $8202 more than RFA while gaining 0.05 QALYs, resulting in an incremental cost-effectiveness ratio of $164,660 per QALY gained. In 1-way sensitivity analyses, results were most sensitive to variation of median survival from both treatments. Stereotactic body radiation therapy was economically reasonable if better survival was presumed (>1 month gain) or if used for large tumors (>4 cm). CONCLUSIONS: If equal survival is assumed, SBRT is not cost-effective compared with RFA for inoperable colorectal liver metastases. However, if better local control leads to small survival gains with SBRT, this strategy becomes cost-effective. Ideally, these results should be confirmed with prospective comparative data.

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.