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Although health-related quality of life (HR-QoL) outcomes are pivotal in oncology, the prognostic significance of patient-reported HR-QoL metrics is largely undefined in localised prostate cancer. We report the association of baseline HR-QoL metrics with overall survival and toxicity in localised prostate cancer.This was a secondary analysis of a phase III randomised controlled study conducted in a single-payer health system. Patients with Gleason score ≤7, clinical stage T1b-T3a and prostate-specific antigen30 ng/ml were randomised to neoadjuvant and concurrent androgen deprivation therapy (ADT) for 6 months starting 4 months before prostate radiotherapy or concurrent and adjuvant ADT for 6 months starting simultaneously with prostate radiotherapy. HR-QoL scores were estimated using the European Organisation for Research and Treatment of Cancer QoL questionnaire. A multistate Markov model was used to determine the association of baseline HR-QoL metrics with overall survival and a multilevel multivariable Cox regression was used to determine the association with the incidence of delayed-onset grade ≥3 radiotherapy-related toxicities. To adjust for multiple analyses, P0.025 was considered as statistically significant.Overall, 393 patients with baseline HR-QoL data were included in this analysis: 194 in the neoadjuvant arm and 199 in the adjuvant arm. Baseline financial difficulty (hazard ratio 1.020, 95% confidence interval 1.010-1.030, P = 0.02) and dyspnoea (hazard ratio 1.020, 95% confidence interval 1.003-1.030, P = 0.01) were associated with inferior overall survival. Baseline dyspnoea was associated with a higher incidence of grade ≥3 toxicity (hazard ratio 1.020, 95% confidence interval 1.010-1.030, P = 0.023).In a cohort of localised prostate cancer patients treated with radiotherapy and short-term ADT, a 10-point higher baseline financial difficulty or dyspnoea was associated with a 20% increased risk of death. With each 10-point increase in baseline dyspnoea, we noted a 20% increase in the associated risk of grade ≥3 delayed-onset radiotherapy-related toxicity.

The objective of these notes is to stress the principles underlying the management of primary lung cancers and other types of malignancies in the thorax-diffuse malignant mesothelioma, invasive mediastinal tumors, chest wall sarcoma, and tracheal neoplasms-and from these considerations to outline a routine scheme for management, which can be followed easily by all staff. It is hoped that by adherence to this routine, adequate and efficient management of all cases will be obtained, both in the very important matter of preoperative preparation, as well in the postoperative management.

Approximately 20% of renal cell carcinoma (RCC) is diagnosed because of paraneoplastic manifestations. RCC has been associated with a large variety of paraneoplastic syndromes (PNS), but it is rarely associated with PNS vasculitis. We present a case of a previously healthy male who presented with systemic vasculitis; bitemporal headaches, diplopia, polyarthritis, palpable purpura, tongue lesion, peri-orbital edema, scleritis, chondritis and constitutional symptoms. He was subsequently found to have oligometastatic RCC. Both his primary lesion and site of oligometastasis were treated with stereotactic radiotherapy (SBRT) and resulted in the resolution of his vasculitis, as well as sustained oncologic response. This is the first case to demonstrate that effective sustained treatment for PNS vasculitis due to oligometastatic RCC is possible with SBRT.

Background To assess correlation of pretreatment specific growth rate (SGR) value of 0.43 × 10‐2 with overall and failure‐free survival of patients with early‐stage non‐small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). Methods A retrospective chart review of 160 patients with pathologically confirmed stage I NSCLC treated with SBRT between June 2010 and December 2012 in a large, tertiary cancer institute was undertaken. Both diagnostic and archived planning CT were uploaded to the treatment planning system to determine tumor volume at diagnosis (GTV1) and planning time (GTV2). The time (t) between both CTs was recorded. SGR was calculated using GTV1, GTV2, and t. The median SGR (0.43 × 10‐2) from our previous data was used to group patients into low and high SGR cohorts. Log‐rank test was used to compare overall (OS) and failure‐free survivals (FFS) of SGR groups. Results The median time interval between diagnostic and planning CT scans was 87 days. The median OS was 38 and 66 months for high and low SGR cohorts, respectively (P = 0.03). The median FFS was 27 and 55 months for high and low SGR cohorts, respectively (P = 0.005). High SGR (P, We demonstrated that tumor growth rate (GR) predicts treatment outcome in early‐stage lung cancer patients treated with SBRT. We used specific growth rate (SGR) as a metric for pretreatment GR and its median (0.43 × 10‐2) to group patients into high and low SGR cohorts. In this study, the same median SGR was validated in an independent dataset at a different cancer institution. Patients with high SGR tumors consistently had significantly lower survival and higher regional failure.

PURPOSE Dose-escalated radiotherapy (RT) with androgen-deprivation therapy (ADT) is a standard definitive treatment of localized prostate cancer (LPCa). The optimal sequencing of these therapies is unclear. Our phase III trial compared neoadjuvant versus concurrent initiation of ADT in combination with dose-escalated prostate RT (PRT). PATIENTS AND METHODS Patients with newly diagnosed LPCa with Gleason score ≤ 7, clinical stage T1b to T3a, and prostate-specific antigen < 30 ng/mL were randomly allocated to neoadjuvant and concurrent ADT for 6 months starting 4 months before RT (neoadjuvant group) or concurrent and adjuvant ADT for 6 months starting simultaneously with RT (concurrent group). The primary end point was biochemical relapse-free survival (bRFS). Stratified log-rank test was used to compare bRFS and overall survival (OS). Incidence of grade ≥ 3 late RT-related toxicities was compared by log-rank test. RESULTS Overall, 432 patients were randomly assigned to the neoadjuvant (n = 215) or concurrent group (n = 217). At 10 years, bRFS rates for the two groups were 80.5% and 87.4%, respectively. Ten-year OS rates were 76.4% and 73.7%, respectively. There was no significant difference in bRFS ( P = .10) or OS ( P = .70) between the two groups. Relative to the neoadjuvant group, the hazard ratio for the concurrent group was 0.66 (95% CI, 0.41 to 1.07) for bRFS and 0.94 (95% CI, 0.68 to 1.30) for OS. No significant difference was observed in the 3-year incidence of late RT-related grade ≥ 3 GI (2.5% v 3.9%) or genitourinary toxicity (2.9% v 2.9%). CONCLUSION In our study, there was no statistically significant difference in bRFS between the two treatment groups. Similarly, no difference was seen in OS or late RT-related toxicities. On the basis of these results, both neoadjuvant and concurrent initiations of short-term ADT with dose-escalated PRT are reasonable standards of care for LPCa.

Both oncologic outcomes and patient-reported outcomes are pivotal in prostate cancer (PCa). However, it remains unknown if there is any association between these 2 outcomes. In this secondary analysis of a randomized controlled trial, we investigated the association of short-term changes in patient-reported outcome with long-term event-free survival (EFS) and metastasis-free survival (MFS) in localized PCa.Localized PCa patients with a Gleason score ≤7, clinical stage T1b to T3a, and prostate-specific antigen (PSA)30 ng/mL were randomized to neoadjuvant and concurrent androgen deprivation therapy (ADT) for 6 months starting 4 months before prostate radiation therapy or concurrent and adjuvant ADT for 6 months starting simultaneously with radiation therapy. Patient-reported symptom burden was evaluated using the European Organisation for Research and Treatment of Cancer quality of life questionnaire (QLQ)-PR.25. Clinically meaningful deterioration (CMD) was defined as a ≥10-point worsening at any time within 10 months postrandomization regardless of subsequent improvement. Landmark analyses were performed to determine the association of CMD of urinary and bowel symptoms separately with EFS and MFS in patients who responded to the baseline questionnaire, were alive, and were event free at 10 months.Overall, 393 patients had responded to the baseline QLQ. One patient died, and 1 patient had failure within 10 months. Therefore, 391 patients were eligible for the landmark analyses. After adjusting for age, Gleason score, PSA, performance status, and treatment group, CMD of urinary symptoms was associated with worse EFS (hazard ratio [HR], 1.79; 95% confidence interval [CI], 1.21-2.65) and MFS (HR, 1.69; 95% CI, 1.11-2.57). Considering deaths as competing events, CMD of urinary symptoms was associated with a significant increase in the relative incidence of progression (subdistribution HR, 2.42; 95% CI, 1.12-5.20). However, no association was found between CMD of bowel symptoms and EFS or MFS.In this study, short-term CMD of urinary symptoms was associated with significantly inferior EFS and MFS and an increase in the relative incidence of progression. Further investigations are needed to explore the biological rationale of such association in the context of ADT and radiation therapy.

Stereotactic Body Radiation Therapy (SBRT) is now accepted as a standard of care for medically inoperable early stage non-small cell lung cancer (NSCLC) [1], [2]. Long term results of retrospective series show excellent local control rates but poor survival with higher rates of distant metastasis despite early stage at presentation [3], [4], [5], [6]. Development of a prognostic tool to recognize factors can allow for stratification to test treatment strategies in future trials and selection of risk appropriate treatment strategies. These prognostic factors could be the bridge from empirical to individualized treatments for this patient population. Previous studies have recognized patient, tumor and treatment related factors associated with overall survival (OS) or distant metastases free survival (DMFS) like the age at presentation, tumor size, histology, radiation dose, maximum standardized uptake value (SUVmax) of the primary tumor and various hematologic parameters [7], [8]. Many studies have evaluated the role of absolute leucocyte, neutrophil, monocyte, lymphocyte or platelet count, ratios of various parameters like neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio among others and found conflicting results and a variety of threshold values with prognostic importance [9], [10], [11], [12], [13], [14]. However, most of these studies have evaluated patients with advanced stage or medically operable early stage NSCLC who underwent surgery. There are very few studies evaluating their role in stage I NSCLC undergoing SBRT [15], [16]. Most of these studies have limited their blood values measured within the 3 month period prior to initiating therapy [9], [10], [11], [12], [13], [15], [17]. Moreover, none of the studies have evaluated the changes in the values of the hematological parameters between pre-SBRT and post-SBRT. Therefore, in our study we evaluated the role of hematologic and other known prognostic factors including the trends of change in the hematological parameters between pre-SBRT and post-SBRT in early stage NSCLC patients treated with SBRT for various survival end points. We included CBC values that were produced within 6 months prior to and after SBRT in order to evaluate if these values show prognostic significance like that of the values within 3 months in other studies.

Purpose The role of prophylactic cranial irradiation (PCI) remains controversial in extensive stage small cell lung cancer (ES-SCLC) with the publication of 2 randomized control trials demonstrating differing outcomes in overall survival. The aim of this study is to determine the impact of PCI on survival and the development of brain metastasis while addressing the disparate use of postchemotherapy brain imaging in the aforementioned trials. Methods and Materials The medical records of 397 consecutive patients with ES-SCLC between Jan. 1, 2005 and Dec. 31, 2011 were retrospectively reviewed. In those eligible patients (n = 155) without baseline brain metastases and who had at least a partial response to chemotherapy, overall survival and time to brain metastasis were estimated using the Kaplan–Meier method comparing patients receiving PCI or not, using both univariate and multivariate analyses. Patients were stratified by their receipt of initial postchemotherapy brain imaging. Follow-up did not include serial brain imaging, which was performed when clinically indicated. Differences between the groups with covariates were analyzed using χ2 statistics and Student's t-tests. Results By multivariate analysis, statistically significant predictors of overall survival were the presence of extrathoracic metastases, performance status and use of PCI. There was a statistically significant difference in overall survival (HR 0.55; 95% CI: 0.39-0.77; P = .0005) and time to brain metastasis (HR 0.40; 95% CI: 0.23-0.66; P = .0004) with the use of PCI. Median survival for the PCI and non-PCI groups was 13.5 and 8.5 months respectively. A survival difference with PCI was observed in both patients that received postchemotherapy brain imaging (HR 0.55; 95% CI: 0.35-0.88; P = .012) and those who did not (HR 0.48; 95% CI: 0.29-0.77; P = .0025). Conclusions PCI in the setting of at least a partial response to chemotherapy was found to have a survival benefit and prolongation of the time to development of brain metastases, when factoring in the use of initial postchemotherapy but not routine surveillance brain imaging.

Radiation remains an important component of mesothelioma treatment in 2018. Its use as a treatment modality continues to evolve as the technology for planning and delivery continues to improve. Use of radiation to improve local control in the involved hemithorax has been a common adjuvant treatment post extrapleural pneumonectomy for many years. Modern treatment options with advanced planning techniques including protons and intensity modulated radiation therapy lead to new potential options for treatment post lung-sparing surgery or in the unresectable setting. Presentations and discussions on the implementation of these strategies for palliation, treatment of oligometastatic recurrence or unresectable disease were the focus of a session dedicated to the role of radiation therapy at the 14th International Conference of the International Mesothelioma Interest Group and are reviewed in this article. Preclinical data to better understand how to integrate radiation and the delivery of novel systemic therapy approached like check point inhibitors are also presented.

Background: Little evidence has been generated for how best to manage patients with non-small-cell lung cancer (NSCLS) presenting with rarer clinical scenarios, including oligometastases, oligoprogression, and pseudoprogression. In each of those scenarios, oncologists have to consider how best to balance efficacy with quality of life, while maximizing the duration of each line of therapy and ensuring that patients are still eligible for later options, including clinical trial enrolment. Methods: An expert panel was convened to define the clinical questions. Using case-based presentations, consensus practice recommendations for each clinical scenario were generated through focused, evidence-based discussions. Results: Treatment strategies and best-practice or consensus recommendations are presented, with areas of consensus and areas of uncertainty identified. Conclusions: In each situation, treatment has to be tailored to suit the individual patient, but with the intent of extending and maximizing the use of each line of treatment, while keeping treatment options in reserve for later lines of therapy. Patient participation in clinical trials examining these issues should be encouraged.

Purpose Although intensity-modulated radiation therapy (IMRT) is increasingly used to treat locally advanced non–small-cell lung cancer (NSCLC), IMRT and three-dimensional conformal external beam radiation therapy (3D-CRT) have not been compared prospectively. This study compares 3D-CRT and IMRT outcomes for locally advanced NSCLC in a large prospective clinical trial. Patients and Methods A secondary analysis was performed to compare IMRT with 3D-CRT in NRG Oncology clinical trial RTOG 0617, in which patients received concurrent chemotherapy of carboplatin and paclitaxel with or without cetuximab, and 60- versus 74-Gy radiation doses. Comparisons included 2-year overall survival (OS), progression-free survival, local failure, distant metastasis, and selected Common Terminology Criteria for Adverse Events (version 3) ≥ grade 3 toxicities. Results The median follow-up was 21.3 months. Of 482 patients, 53% were treated with 3D-CRT and 47% with IMRT. The IMRT group had larger planning treatment volumes (median, 427 v 486 mL; P = .005); a larger planning treatment volume/volume of lung ratio (median, 0.13 v 0.15; P = .013); and more stage IIIB disease (30.3% v 38.6%, P = .056). Two-year OS, progression-free survival, local failure, and distant metastasis–free survival were not different between IMRT and 3D-CRT. IMRT was associated with less ≥ grade 3 pneumonitis (7.9% v 3.5%, P = .039) and a reduced risk in adjusted analyses (odds ratio, 0.41; 95% CI, 0.171 to 0.986; P = .046). IMRT also produced lower heart doses ( P < .05), and the volume of heart receiving 40 Gy (V40) was significantly associated with OS on adjusted analysis ( P < .05). The lung V5 was not associated with any ≥ grade 3 toxicity, whereas the lung V20 was associated with increased ≥ grade 3 pneumonitis risk on multivariable analysis ( P = .026). Conclusion IMRT was associated with lower rates of severe pneumonitis and cardiac doses in NRG Oncology clinical trial RTOG 0617, which supports routine use of IMRT for locally advanced NSCLC.

Introduction Concurrent thoracic radiation and platinum-based chemotherapy is the standard of care for treatment of unresectable stage IIIA-IIIB non–small-cell lung cancer (NSCLC), but the optimal drug regimen has not been established. Patients and Methods In the present single-arm phase II trial, patients with previously untreated, unresectable stage IIIA-IIIB NSCLC (all histologic types) were treated with pemetrexed-cisplatin (500 mg/m 2 intravenously on days 1 and 22, 20 mg/m 2 intravenously on days 1-5 and days 22-26) concurrent with radiotherapy (61-66 Gy in 31-35 fractions), followed by 2 cycles of consolidation pemetrexed-cisplatin (75 mg 2 ) therapy. The primary endpoint was the 1-year overall survival (OS) rate. The study treatment was considered active if the 1-year OS rate was ≥ 70%. Results A total of 39 patients, including 6 from the previous phase I trial who had been treated at the recommended phase II dose, were eligible for analysis. The most common drug-related grade 3 to 4 adverse events during the concurrent phase were hematologic and 5.1% of patients experienced grade 3 esophagitis. The response rate was 45.9% (17 of 37 patients), with no complete responses. The 1-, 2-, and 3-year OS survival rates were 79.5%, 56.4%, and 46.2%, respectively. The median OS, time to progressive disease, and progression-free survival was 30.3, 13.7, and 11.8 months, respectively. Conclusion Full-dose cisplatin and pemetrexed can be administered concurrently with conventional doses of thoracic radiation. The median and 1-year OS rates were favorable compared with published clinical trials in this setting. The regimen was tolerable, and the toxicity profile was consistent with the known toxicity profiles of pemetrexed, cisplatin, and radiation.

Background: The prediction of local recurrence (LR) of stage I non-small cell lung cancer (NSCLC) after de nitive stereotactic body radiotherapy (SBRT) remains elusive. The purpose of this study was to assess whether quantitative imaging features on pre-treatment computed tomography (CT) can predict LR beyond 18 ( 18 F) uorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/CT maximum standard uptake value (SUV max ). Methods: This retrospective study evaluated 36 patients with 37 stage I NSCLC who had local tumor control (LC; n=19) and (LR; n=18). Textural features were extracted on pre-treatment CT. Mann-Whitney U tests were used to compare LC and LR groups. Receiver-operating characteristic (ROC) curves were constructed and the area under the curve (AUC) calculated with LR as outcome. Results: Gray-level correlation and sum variance were greater in the LR group, compared with the LC group (P=0.02 and P=0.04, respectively). Gray-level difference variance was lower in the LR group (P=0.004). The logistic regression model generated using gray-level correlation and difference variance features resulted in AUC (SE) 0.77 (0.08) (P=0.0007). The addition of 18F-FDG PET/CT SUV max did not improve the AUC (P=0.75). Conclusions: CT textural features were found to be predictors of LR of early stage NSCLC on baseline CT prior to SBRT.

Author(s): Cheng, Ting-Yuan David; Darke, Amy K; Redman, Mary W; Zirpoli, Gary R; Davis, Warren; Payne Ondracek, Rochelle; Bshara, Wiam; Omilian, Angela R; Kratzke, Robert; Reid, Mary E; Molina, Julian R; Kolesar, Jill M; Chen, Yuhchyau; MacRae, Robert M; Moon, James; Mack, Philip; Gandara, David R; Kelly, Karen; Santella, Regina M; Albain, Kathy S; Ambrosone, Christine B | Abstract: Background:To what extent steroid hormones contribute to lung cancer in male and female never smokers and smokers is unclear. We examined expression of hormone receptors in lung tumors by sex and smoking. Methods:Patients with primary non-small cell lung cancer were recruited into an Intergroup study in the United States and Canada, led by SWOG (S0424). Tumors from 813 cases (450 women and 363 men) were assayed using immunohistochemistry for estrogen receptor (ER)-α, ER-β, progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Linear regression was used to examine differences in expression by sex and smoking status. Cox proportional hazard models were used to estimate survival associated with the receptors. All statistical tests were two-sided. Results:In ever smokers, postmenopause and oral contraceptive use were associated with lower nuclear ER-β (P = .02) and total (nuclear + cytoplasmic) PR expression (P = .02), respectively. Women had lower cytoplasmic ER-α (regression coefficient [β], or differences in H-scores = -15.8, P = .003) and nuclear ER-β (β = -12.8, P = .04) expression than men, adjusting for age, race, and smoking. Ever smokers had both higher cytoplasmic ER-α (β = 45.0, P l .001) and ER-β (β = 25.9, P l .001) but lower total PR (β = -42.1, P l .001) than never smokers. Higher cytoplasmic ER-α and ER-β were associated with worse survival (hazard ratio = 1.73, 95% confidence interval [CI] = 1.15 to 2.58, and HR = 1.59, 95% CI = 1.08 to 2.33, respectively; quartiles 4 vs 1). Conclusions:Lower expression of nuclear ER-β in women supports the estrogen hypothesis in lung cancer etiology. Increasing cytoplasmic ER-α and ER-β and decreasing PR protein expression may be mechanisms whereby smoking disrupts hormone pathways.

Purpose In this single institution retrospective study of patients with stage I medically inoperable non-small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SABR) we attempt to model overall survival (OS) using initial prognostic variables with specific attention on the Charlson co-morbidity index (CCI). Methods Between 2008 and 2013, 335 patients with medically inoperable stage I NSCLC were treated with SABR or hypofractionated radiotherapy (50–60 Gy in at least 5 Gy or 4 Gy fractions respectively) at our institution. Medical comorbidities and Charlson scores were determined by individual chart review. Patients were stratified into 3 groups based on the CCI score (0–1, 2–3, 4–9) and again based on the age-adjusted Charlson Comorbidity score (aCCI). Cumulative survival for each stratum was determined using the Kaplan-Meier method. Non-significant and confounding variables were identified and discounted from survival modeling. 3 sex stratified Cox regression models were tested: (1) aCCI with age and comorbidity combined; (2) age and CCI; (3) age alone, comorbidity removed. Results The median survival was 4.4 years and the median follow up 4.7 years. The median CCI and aCCI scores were 2 and 5 respectively. Patients with aCCI 7–12 had an increased hazard of death on univariate analysis HR 2.45 (1.15–5.22 95%CI, p = 0.02) and -excluding age as a competing variable- on multivariate analysis HR 2.25 (1.04–4.84 95%CI, p = 0.04). Patients with CCI 4-9 had an increased hazard of death on univariate analysis HR 1.57(1.30–2.90) but not on multivariate analysis. On formalized testing – with either continuous or categorical variables- all three survival models yielded similar coefficients of effect. Conclusion We identify male gender, weight loss greater than 10% and age as independent prognostic factors for patients treated with medically inoperable NSCLC treated with SABR or hypofractionated radiotherapy. Based on our survival models, age alone can be used interchangeably with aCCI or CCI plus age with the same prognostic value. Age is more reliably recorded, less prone to error and therefore a more useful metric than Charlson score in this group of patients.

Background Many patients diagnosed with stage IIIB (AJCC sixth edition; T4, N3, or both; no pleural effusion) non–small-cell lung cancer (NSCLC) are treated with curative intent, despite a low cure rate. Guidelines are required to help select patients for radical therapy so that the patients with little chance of cure may be spared the toxicities of aggressive treatment. A retrospective analysis was performed to investigate factors influencing outcomes in these patients. Materials and Methods From 2002 to 2009, all cases of stage IIIB NSCLC from the authors' institution were identified. Patients treated with radical radiotherapy (minimum dose, 50 Gy), with or without chemotherapy, were included. Charts were reviewed for patient demographic data, baseline blood work, tumor factors, treatment factors, and hospitalizations. The primary outcome was overall survival (OS), measured from time of diagnosis. Results Of 238 patients identified, 184 eligible cases were reviewed. The median follow-up for all patients was 17.2 months (range, 1.7-237.1). The median progression-free survival was 10.8 months (95% CI, 9.6-12.4). Median survival was 17.9 months, and OS was 68%, 42%, and 28% at 1, 2, and 3 years, respectively. In multivariate analysis, female gender (hazard ratio [HR], 0.58; 95% CI, 0.37-0.88; P = .0013), ≤ 5% weight loss (HR, 0.64; 95% CI, 0.43-0.93; P = .01), and absence of N3 disease (HR, 0.64; 95% CI, 0.42-0.96; P = .03) were associated with significantly longer survival. Conclusion OS was significantly longer in women, in patients with ≤ 5% weight loss, and in those without N3 disease. Good patient selection remains important in the radical treatment of stage IIIB NSCLC.

Purpose The aim of this study was to determine whether the preradiation maximum standardized uptake value (SUV max ) of the primary tumor for [ 18 F]-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) has a prognostic significance in patients with Stage T1 or T2N0 non-small cell lung cancer (NSCLC) treated with curative radiation therapy, whether conventional or stereotactic body radiation therapy (SBRT). Methods and Materials Between January 2007 and December 2011, a total of 163 patients (180 tumors) with medically inoperable histologically proven Stage T1 or T2N0 NSCLC and treated with radiation therapy (both conventional and SBRT) were entered in a research ethics board approved database. All patients received pretreatment FDG-PET / computed tomography (CT) at 1 institution with consistent acquisition technique. The medical records and radiologic images of these patients were analyzed. Results The overall survival at 2 years and 3 years for the whole group was 76% and 67%, respectively. The mean and median SUV max were 8.1 and 7, respectively. Progression-free survival at 2 years with SUV max max ≥7 (67% vs 51%; P =.0096). Tumors with SUV max ≥7 were associated with a worse regional recurrence-free survival and distant metastasis-free survival. In the multivariate analysis, SUV max ≥7 was an independent prognostic factor for distant metastasis-free survival. Conclusion In early-stage NSCLC managed with radiation alone, patients with SUV max ≥7 on FDG-PET / CT scan have poorer outcomes and high risk of progression, possibly because of aggressive biology. There is a potential role for adjuvant therapies for these high-risk patients with intent to improve outcomes.

The role of prophylactic cranial irradiation (PCI) for extensive-stage small-cell lung cancer (ES-SCLC) has evolved since the publication of two phase III randomized control trials in the past decade. Despite significant evidence demonstrating improvements in survival and rates of developing brain metastasis in the limited-stage setting, there was no clear evidence supporting its use for ES-SCLC until 2007, with the publication of the European Organization for Research and Treatment of Cancer (EORTC) study.

Background Even if non–small-cell lung cancer (NSCLC) is diagnosed early and resected, recurrence is common. Uncertainty exists about the optimal treatment of locoregional recurrence. In fit patients with locoregional recurrence, chemoradiotherapy is sometimes offered, but no data exist about the feasibility and efficacy of this approach. We retrospectively collected data from patients treated this way to assess their outcomes and to identify prognostic factors. Patients and Methods Databases of The Ottawa Hospital Cancer Centre (TOHCC) (N = 5791) and the Princess Margaret Hospital (PMH) (N = 2225) were screened to identify patients with recurrent NSCLC after curative resection who were offered curative-intent chemoradiotherapy. Selected patients' charts were reviewed. Results Thirty patients fit our search criteria. The median disease-free interval was 15 months (2-33 months) and stage at recurrence was mainly T0 (n = 25 [83%]), N2 (n = 25 [83%]), and M0 (n = 29 [97%]). The median radiation dose given at recurrence was 63.5 Gy (26-66 Gy). Chemotherapy included a platinum agent in all cases, mostly a platinum-vinorelbine doublet (n = 14 [47%]), at a median of 3 cycles, (1-6 cycles) 2 of which were concurrent (0-3 cycles). Toxicities were as expected from thoracic chemoradiotherapy, with 7 cases of grade 4 toxicities and no treatment-related deaths. Median follow-up was 22 months (1.5-88 months). Median survival after recurrence was 26.9 months. No prognostic factors were identified. Conclusion Chemoradiotherapy for locoregional recurrent NSCLC is practiced sporadically. This treatment is feasible for highly selected patients, and in our cohort, it allowed for a significantly higher than expected survival. No prognostic factors were identified. Chemoradiotherapy for locoregional NSCLC should be examined in a prospective trial.

TO THE EDITOR: We write about the Grand Rounds case discussion by Sonpavde et al in a recent issue of Journal of Clinical Oncology. The discussion illustrates the twin challenges presented by locally advanced urothelial bladder cancer. The first challenge, which was covered well in the detailed review, is the risk of distant metastases. This risk is mitigated by a 5% survival gain with neoadjuvant chemotherapy and a disease-free survival gain with adjuvant chemotherapy. What is missing from the discussion is the second oncologic challenge of pelvic recurrence. In the presented patient case, the eventual pT3N1 stage gave the patient a 15% to 30% risk of pelvic recurrence either in isolation or, more likely, together with distant relapse. This pelvic failure rate has been demonstrated in multi-institutional case series, individual institutional series, and the two large randomized trials of neoadjuvant chemotherapy, which all demonstrated that chemotherapy unfortunately does not reduce the pelvic recurrence rate. This pelvic failure is an absolute ceiling on potential curability and also can be a source of significant clinical morbidity. Bladder cancer remains the one cancer for which optimization of locoregional control with multimodality therapy has not been studied rigorously. That is now set to change with the currently accruing NRG GU001 trial, which is a phase II randomized study of postoperative adjuvant radiotherapy in this setting. If all other solid tumors can be taken as an example, it is likely that bladder cancer too will benefit from the best of surgery, adjuvant radiotherapy, and systemic treatment. It is by offering patients the possibility of enrollment into this and other trials that we will improve the outlook for this disease. To finish by returning to the presented patient case: It so happens that, in the interest of safety, the NRG trial currently excludes patients with a neo bladder, so systemic treatment is the sole active, treatment option. If the patient did not have a neoadjuvant bladder, he would have been eligible for the radiation trial even if he received systemic adjuvant treatment postoperatively.

To retrospectively compare the sensitivity of image-guided core-needle biopsy, thoracoscopy, and thoracotomy in the diagnosis of malignant pleural mesothelioma and to retrospectively determine the incidence of needle track seeding after these procedures.Institutional review board approval was obtained, and informed consent was not required. The study included 100 consecutive patients (81 men, 19 women; average age, 65.8 years) with pathologically proved malignant pleural mesothelioma who were treated between 1994 and 2002. A total of 23 core-needle biopsies were performed in 22 patients, and 11 of these biopsies were coupled with fine-needle aspiration biopsy. A coaxial technique was used, and biopsy was performed with fluoroscopic (12 biopsies), computed tomographic (10 biopsies), or ultrasonographic (one biopsy) guidance. Sixty-nine patients underwent surgical biopsy in the form of thoracoscopy (n = 51) and/or thoracotomy (n = 21). Patients were followed up clinically for any evidence of needle track seeding after image-guided or surgical procedures. The sensitivity of diagnostic procedures and the incidence of needle track seeding as a result of intervention were calculated.Sensitivity was 86% for image-guided core-needle biopsy, 94% for thoracoscopy, and 100% for thoracotomy. The incidence of needle track seeding was 4% for image-guided core-needle biopsy and 22% for surgical biopsy.Image-guided core-needle biopsy in patients with malignant pleural mesothelioma has a lower incidence of needle track seeding than surgical biopsy and has a high sensitivity for diagnosis.

Purpose: To investigate a putative increased risk of rectal cancer subsequent to prostatic radiotherapy. Methods and Materials: In an analysis of the Surveillance, Epidemiology, and End Results registry, we compared men who had radiotherapy for prostatic carcinoma with those treated surgically and those treated with neither modality. Kaplan-Meier analyses for the time to failure from rectal cancer were performed between age-matched subgroups of the three cohorts. Cox proportional hazards analyses were performed to ascertain what influences might affect the incidence of subsequent rectal cancer. Results: In all, 33,831 men were irradiated, 167,607 were treated surgically, and 36,335 received neither modality. Rectal cancers developed in 243 (0.7%) of those irradiated (mean age, 70.7 years), 578 (0.3%) of those treated surgically (68.7 years), and 227 (0.8%) of those treated with neither modality (74.2 years). When age effects and the differences between the surgical and untreated cohorts were controlled for, we were unable to demonstrate any significant increased incidence of rectal cancer in men irradiated for prostatic cancer. Conclusions: An increased frequency of rectal cancer after prostatic irradiation, apparent on crude analysis, could be attributed to age confounding and other unmeasured confounders associated with prostate cancer treatment and rectal cancer risk.

Importance A recent randomized radiation dose–escalation trial in unresectable stage III non–small-cell lung cancer (NSCLC) (Radiation Therapy Oncology Group [RTOG] 0617) showed a lower survival rate in the high-dose radiation therapy (RT) arm (74 Gy) than in the low-dose arm (60 Gy) with concurrent chemotherapy. Objective The primary QOL hypothesis predicted a clinically meaningful decline in quality of life (QOL) via the Functional Assessment of Cancer Therapy (FACT)–Lung Cancer Subscale (LCS) in the high-dose RT arm at 3 months. Design, Setting, and Patients The RTOG 0617 trial was a randomized phase 3 study (conducted from November 2007 to November 2011) in stage III NSCLC using a 2 × 2 factorial design and stratified by histology, positron emission tomography staging, performance status, and irradiation technique (3-dimensional conformal RT [3D-CRT] vs intensity-modulated RT [IMRT]). A total of 185 institutions in the United States and Canada took part. Of 424 eligible patients with stage III NSCLC randomized, 360 (85%) consented to QOL evaluation, of whom 313 (88%) completed baseline QOL assessments. Intervention Treatment with 74-Gy vs 60-Gy RT with concurrent and consolidation carboplatin/paclitaxel with or without cetuximab. Main Outcomes and Measures The QOL data were collected prospectively via FACT Trial Outcome Index (FACT-TOI), calculated as the sum of the following measures: Physical Well Being (PWB), Functional Well Being (FWB), and the LCS. Data are presented at baseline and 3 and 12 months via minimal clinically meaningful changes of 2 points or more for PWB, FWB, and LCS or 5 points or more for TOI. Results Of the 313 patients who completed baseline QOL assessments, 219 patients (70%) completed the 3-month QOL assessments, and 137 of the living patients (57%) completed the 12-month assessment. Patient demographics and baseline QOL scores were comparable between the 74-Gy and 60-Gy arms. Significantly more patients in the 74-Gy arm than in the 60-Gy arm had clinically meaningful decline in FACT-LCS at 3 months (45% vs 30%; P = .02). At 12 months, fewer patients who received IMRT (vs 3D-CRT) had clinically meaningful decline in FACT-LCS (21% vs 46%; P = .003). Baseline FACT-TOI was associated with overall survival in multivariate analysis. Conclusions and Relevance Despite few differences in clinician-reported toxic effects between treatment arms, QOL analysis demonstrated a clinically meaningful decline in QOL in the 74-Gy arm at 3 months, confirming the primary QOL hypothesis. Baseline QOL was an independent prognostic factor for survival. Trial Registration clinicaltrials.gov Identifier:NCT00533949

To evaluate the feasibility and safety of concurrent pemetrexed/cisplatin/thoracic radiotherapy followed by consolidation pemetrexed/cisplatin for unresectable Stage IIIA/B non-small-cell lung cancer (NSCLC).Eligible patients with5% weight loss and good performance status received two cycles of pemetrexed (300, 400, or 500 mg/m(2) on Days 1 and 22 for Dose Levels 1, 2, and 3/4, respectively) and cisplatin (25 mg/m(2) Days 1-3 for Dose Levels 1-3; 20 mg/m(2) Days 1-5 for Dose Level 4) concurrent with thoracic radiation (61-66 Gy in 31-35 fractions). Consolidation consisted of two cycles of pemetrexed/cisplatin (500 mg/m(2), 75 mg/m(2)) 21 days apart, after concurrent therapy.Between January 2006 and October 2007, 16 patients entered the study. Median follow-up was 17.2 months. No dose-limiting toxicities were observed. Median radiation dose was 64 Gy (range, 45-66 Gy). Rates of significant Grade 3/4 hematologic toxicity were 38% and 7%, respectively. One patient experienced Grade 3 acute esophagitis, and 2 experienced late (Grade 3) esophageal stricture, successfully managed with dilation. One patient experienced Grade 3 pneumonitis. The overall response rate was 88%. One-year overall survival was 81%.Full systemic dose pemetrexed seems to be safe with full-dose cisplatin and thoracic radiation in Stage IIIA/B NSCLC. Pemetrexed is the first third-generation cytotoxic agent tolerable at full dose in this setting. A Phase II study evaluating Dose Level 4 is ongoing.

Background:Anemia during chemoradiation is associated with poorer outcomes in various cancers. Concurrent chemoradiation (CCRT) is standard therapy for fit patients with limited small-cell lung cancer (LD-SCLC). The objective of this study was to explore the relationship between anemia and treatment outcomes in patients with LD-SCLC treated with CCRT.Methods:Charts of all patients with LD-SCLC receiving CCRT at The Ottawa Hospital Regional Cancer Centre between January 1996 and December 2002 were reviewed. Information extracted included demographics, known prognostic factors, treatment details, and hemoglobin values from diagnosis until the completion of therapy. Factors associated with outcomes were determined by Cox regression analyses.Results:One hundred thirty patients were eligible for inclusion, and their median survival was 18.1 months (95% CI, 14.8–25.1 months). By univariate analysis, poorer outcome was associated with Eastern Cooperative Oncology Group performance status ≥2, supraclavicular adenopathy, and pre-radiotherapy hemoglobin

Chemoradiotherapy has become the standard treatment for patients with locally advanced non-small-cell lung cancer on the basis of several large randomized trials. Despite an increase in median survival from 10 months with radiotherapy alone to 16 to 17 months with concurrent chemoradiotherapy, long-term survival in this disease remains modest at best. With the advent of new biologic agents targeting specific cellular pathways associated with malignant progression, combined-modality therapy has the potential to target tumors selectively with less toxicity.

7087 Background: Concurrent chemoRT is standard of care for most patients with unresectable stage III A/B NSCLC but no standard chemotherapy regimen/schedule has been established. In a previous pha...

We have developed a method that leverages the image‐guidedradiotherapy capabilities of a tomotherapy unit to adapt daily treatments to changes in bladder shape and volume. Each patient receives three treatment‐planningCT scans: empty bladder; partially full bladder; and full bladder. For each scan, the radiation oncologist contours the initial and boost target volumes (PTV1 and PTV2) and organs at risk, and an initial treatment plan is generated to deliver 40 Gy in 20 fractions to PTV1. A second treatment plan is designed to deliver 20 Gy in 10 fractions to PTV2 (a total of six treatment plans per patient). Patients are asked to void immediately before each treatment. An MVCT of the pelvis is performed before each fraction to verify patient position and to assess the bladder volume. If the treating therapist concludes that the patient's bladder extends to within 10 mm of the PTV contour, then the corresponding treatment plan for a larger bladder volume is downloaded and the MVCT is repeated. Approximately 20% of fractions required a treatment change based on perceived bladder volume. Three of four patients treated to‐date have required the use of a larger volume treatment plan at least once, even though they are always instructed to empty their bladders just prior to treatment. Our early experience is that relying on patient compliance for treating “empty bladder” is insufficient to ensure proper target coverage, and that generous internal margins are required to ensure target coverage in the absence of adaptive IGRT capability.

ganciclovir (GCV) in CAR and CARbladder cancer cells. The efficacy of combination therapy was evaluated using increasing MOI’s (multiplicity of infections) of Ad5/F35HSV-tk followed by a single dose of radiation (2.5 Gy) that was delivered prior to initiation of GCV (ganciclovir) treatment. The MTT assay was used to assess cell viability. Induction of apoptosis was evaluated by annexin V-FITC. The effect on cell cycle and induction of apoptosis were analyzed using flow cytometry.

Since the 1960s, the incidence of malignant mesothelioma in Canada has increased dramatically because of work-related asbestos exposures. Treatment options are limited. Although chemotherapy is now an accepted standard in the management of advanced disease, uncertainty surrounds the roles of radical surgery and radiation. In March 2007, a symposium was held in Vancouver, B.C., to review the current approach to malignant mesothelioma in Canada and to discuss development of a national clinical research strategy.