Surgery versus stereotactic body radiation therapy for stage I non-small cell lung cancer: A comprehensive review.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in the United States. With the implementation of lung cancer screening, the number and proportion of patients diagnosed with early-stage disease are anticipated to increase. Surgery is currently the standard of care for patients with operable stage I NSCLC. However, promising outcomes with stereotactic body radiation therapy (SBRT) in patients with inoperable disease has led to interest in directly comparing SBRT and surgery in operable patients. Unfortunately, early randomized trials comparing surgery and SBRT closed early because of poor accrual. In this article, the nuances of surgery and SBRT for early-stage NSCLC are reviewed. Furthermore, retrospective and prospective analyses of SBRT in early-stage NSCLC are discussed, and active randomized trials comparing these 2 approaches are described. Cancer 2018;124:667-78. © 2017 American Cancer Society.

Smoking history predicts for increased risk of second primary lung cancer: a comprehensive analysis.

BACKGROUND: Tobacco use is the most important risk factor for the development of lung cancer. The objective of the current study was to determine the effect of smoking on the development of second primary lung cancers (SPLCs) and other clinical outcomes after surgery for non-small cell lung cancer (NSCLC). METHODS: All patients who underwent surgery for NSCLC at the study institution from 1995 through 2008 were identified. Rates of SPLC were analyzed based on smoking status and pack-year exposure. Multivariate analysis was performed to determine risk factors for SPLC. Overall survival, local control, distant metastases, and postoperative mortality were also examined. RESULTS: A total of 1484 patients were identified, including 98 never-smokers. The incidence of SPLC at 3 years, 5 years, and 8 years was 5%, 8%, and 16%, respectively. Only 1 never-smoker developed an SPLC. On multivariate analysis, which was restricted to ever-smokers with pack-years as a continuous variable, smoking history was found to be the only independent risk factor for SPLC (hazard ratio, 1.08; 95% confidence interval, 1.02-1.16 [P = .031]), corresponding to an 8% increased risk per 10 pack-year exposure. There were no differences in rates of local control or distant metastases based on smoking status. There was a trend toward lower postoperative mortality in never-smokers compared with ever-smokers (0% vs 3.3%; P = .069). Overall survival was found to be significantly worse for current smokers compared with former and never-smokers. CONCLUSIONS: SPLCs are rare in never-smokers. Increasing tobacco exposure is associated with a higher risk of SPLC in patients with a history of smoking. Current smokers have an increased risk of mortality whereas former and never-smokers have comparable survival.

Early outcomes of empiric embolization of tumor-related gastrointestinal hemorrhage in patients with advanced malignancy.

PURPOSE: To report short-term results of empiric transcatheter embolization for patients with advanced malignancy and gastrointestinal (GI) hemorrhage directly from a tumor invading the GI tract wall. MATERIALS AND METHODS: Between 2005 and 2011, 37 mesenteric angiograms were obtained in 26 patients with advanced malignancy (20 men, six women; mean age, 56.2 y) with endoscopically confirmed symptomatic GI hemorrhage from a tumor invading the GI tract wall. Angiographic findings and clinical outcomes were retrospectively evaluated. Clinical success was defined as absence of signs and symptoms of hemorrhage for at least 30 day following embolization. RESULTS: Active extravasation was demonstrated in three cases. Angiographic abnormalities related to a GI tract tumor were identified on 35 of 37 angiograms, including tumor neovascularity (n = 21), tumor enhancement (n = 24), and luminal irregularity (n = 5). In the absence of active extravasation, empiric embolization with particles and/or coils was performed in 25 procedures. Cessation of hemorrhage (ie, clinical success) occurred more frequently when empiric embolization was performed (17 of 25 procedures; 68%) than when embolization was not performed (two of nine; 22%; P = .03). Empiric embolization resulted in clinical success in 10 of 11 patients with acute GI bleeding (91%), compared with seven of 14 patients (50%) with chronic GI bleeding (P = .04). No ischemic complications were encountered. CONCLUSIONS: In patients with advanced malignancy, in the absence of active extravasation, empiric transcatheter arterial embolization for treatment of GI hemorrhage from a direct tumor source demonstrated a 68% short-term success rate, without any ischemic complications.

Postoperative Radiation Therapy for Prostate Cancer: Comparison of Conventional Versus Hypofractionated Radiation Regimens.

PURPOSE: To compare acute/late toxicity and biochemical control in contemporaneous prostate cancer patient cohorts treated with hypofractionated postprostatectomy radiation therapy (hypoPORT) or conventional PORT (coPORT). METHODS AND MATERIALS: Consecutive patients treated with intensity modulated hypoPORT (2.5 Gy per fraction, median cumulative dose 65 Gy [range, 57.5-70 Gy]) or coPORT (1.8-2.0 Gy per fraction, median cumulative dose 66 Gy [range, 60-74 Gy]) between 2005 and 2016 at 2 institutions constituted the study cohort. Acute toxicity and cumulative late grade 2 and ≥3 genitourinary (GU) and gastrointestinal (GI) toxicity incidences were calculated for all patients using the Kaplan-Meier method and compared between cohorts. Biochemical progression-free survival (bPFS) was calculated in patients with ≥12 months' follow-up. RESULTS: Median follow-up for all 461 patients was 38.6 months. Of the 461 patients, 167 (36%) received hypoPORT, and 294 (64%) patients received coPORT. The hypoPORT cohort had significantly worse baseline urinary incontinence. Acute grade ≥2 GU toxicity was more common after hypoPORT (22% vs 8%) (P = .0001). Late grade ≥3 GU toxicity cumulative incidence at 6 years was 11% (hypoPORT) and 4% (coPORT) (P = .0081). However, hypoPORT was not associated with late grade ≥2 GU toxicity on multivariate analysis (hazard ratio 1.39, 95% confidence interval 0.86-2.34) (P = .18). There was no difference in acute or late GI toxicity. In the subset of patients with ≥12 month's follow-up (n = 364, median follow-up 52 months), 4-year bPFS was 78% (95% CI 69.4-85.0) after hypoPORT (P = .0038) and 65% (95% CI 57.6-71.1) after coPORT. HypoPORT was not significant for bPFS on multivariate analysis (hazard ratio 0.64, 95% CI 0.41-1.02, P = .059). CONCLUSIONS: HypoPORT shows promising early biochemical control. After controlling for baseline urinary function, hypoPORT was not associated with greater GU toxicity than coPORT. © 2018 Elsevier Inc.

Intratreatment Response Assessment With 18F-FDG PET: Correlation of Semiquantitative PET Features With Pathologic Response of Esophageal Cancer to Neoadjuvant Chemoradiotherapy.

PURPOSE: This prospective study seeks to extract semiquantitative positron emission tomography (PET) features from 18F-fluorodeoxyglucose PET scans performed before and during neoadjuvant chemoradiotherapy for esophageal cancer and to compare their accuracy in predicting histopathologic response. METHODS AND MATERIALS: From 2012 to 2016, 26 patients with esophageal cancer underwent pretreatment and intratreatment PET scans during chemoradiotherapy followed by surgery. Median patient age was 63 years (interquartile range, 58-68 years); 26 patients had esophageal adenocarcinoma, and 3 had esophageal squamous cell carcinoma. The intratreatment PET scan was performed at a median of 32.4 Gy (interquartile range, 30.6-32.4 Gy). PET features of the primary site including maximum standardized uptake value (SUV), SUV mean, metabolic tumor volume, and total lesion glycolysis were extracted from the pretreatment and intratreatment PET scans. Patients were histopathologic responders if there was complete or near-complete tumor response by modified Ryan scheme. Mean values of PET features were compared between histopathologic responders and nonresponders. The area under the receiver operating characteristic curve (AUC) was used to compare the accuracy of PET features in predicting histopathologic response. RESULTS: Eleven patients (42%) were histopathologic responders. PET features most discriminatory of histopathologic response on AUC analysis were volumetric PET features from the intratreatment PET including metabolic tumor volume based on manual contour (AUC, 0.73; 95% confidence interval, 0.52-0.93) and total lesion glycolysis based on semiautomatic 40% SUV threshold (AUC, 0.73; 95% confidence interval, 0.53-0.94). CONCLUSIONS: Volumetric PET features from the intratreatment PET were the most accurate predictors of histopathologic response.

Plasma Metabolites and Risk of Radiation-induced Esophagitis: A Secondary Analysis from a Prospective Study.

AIM: Metabolic profiling was performed on plasma samples obtained prior to and during radiation therapy (RT) for locally advanced lung cancer to identify metabolites predictive of RT-induced esophagitis. PATIENTS AND METHODS: Patients received cisplatin/etoposide with RT as part of a prospective dose-escalation study (n=24). Plasma samples were collected at baseline, weeks 2 and 5 during RT, and 6 weeks post-RT. Metabolites were measured by ultrahigh-performance liquid chromatography-tandem mass spectroscopy at each time-point. Metabolite concentrations were compared between patients developing grade 0-1 and those with grade 2 or more esophagitis. RESULTS: At baseline, 23 metabolites differed significantly (p<0.05) between patients with grade 0-1 esophagitis and those with grade 2 or esophagitis. Sixty-seven metabolites were different at week 2. None reached statistical significance (q<0.05) after corrections for multiple comparisons. On random forest modeling, the predictive accuracy of the metabolite data was 33% at baseline and 50% at 2 weeks. CONCLUSION: No individual metabolite or group of metabolites was predictive of acute RT-induced esophagitis.

Patterns of Distant Metastases After Surgical Management of Non-Small-cell Lung Cancer.

BACKGROUND: Patients with limited metastases, oligometastases (OMs), might have improved outcomes compared with patients with widespread distant metastases (DMs). The incidence and behavior of OMs from non-small-cell lung cancer (NSCLC) need further characterization. PATIENTS AND METHODS: The medical records of patients who had undergone surgery for stage I-III NSCLC from 1995 to 2009 were retrospectively reviewed. All information pertaining to development of the first metastatic progression was recorded and analyzed. Patients with DMs were categorized into OMs (1-3 lesions potentially amenable to local therapy) and DM subgroups. RESULTS: Of 1719 patients reviewed, 368 (21%) developed DMs with a median follow-up period of 39 months. A single lesion was diagnosed in 115 patients (31%) and 69 (19%) had 2 to 3 lesions (50% oligometastatic). The median survival from the DM diagnosis for oligometastatic and diffuse DM was 12.4 and 6.1 months, respectively (hazard ratio, 0.54; 95% confidence interval, 0.42-0.68; P < .001). Patients with a single metastasis had the longest median survival at 14.7 months. Younger age, OM, the use of chemotherapy for the primary tumor, and DM detection by surveillance imaging were independently associated with improved survival. CONCLUSION: DMs and OMs are common in surgically managed NSCLC. Overall survival appears to be prolonged with OM.

Patterns of Failure After Surgery for Non-Small-cell Lung Cancer Invading the Chest Wall.

INTRODUCTION: The patterns of failure after resection of non-small-cell lung cancer (NSCLC) invading the chest wall are not well documented, and the role of adjuvant radiation therapy (RT) is unclear, prompting the present analysis. MATERIALS AND METHODS: The present institutional review board-approved study evaluated patients who had undergone surgery from 1995 to 2014 for localized NSCLC invading the chest wall. Patients with superior sulcus tumors were excluded. The clinical outcomes were estimated using the Kaplan-Meier method and compared using a log-rank test. The prognostic factors were assessed using a multivariate analysis, and the patterns of failure were scored. RESULTS: Seventy-four patients were evaluated. Most patients had undergone lobectomy or pneumonectomy (85%) with en bloc chest wall resection (80%) and had pathologically node negative findings (81%). The surgical margins were positive in 10 patients (14%) and most commonly involved the chest wall (7 of 10). Adjuvant treatment included RT in 21 (28%) and chemotherapy in 28 (38%). A total of 24 local recurrences developed. The chest wall was a component of local disease recurrence in 19 of 24 cases (79%). The local control rate at 5 years for the entire population was 60% (95% confidence interval, 46%-74%). The local control rate was 74% with adjuvant RT versus 55% without RT (P = .43). On multivariate analysis, only resection less than lobectomy or pneumonectomy was associated with worse local control. The overall survival rate was 38% with RT versus 34% without RT (P = .59). CONCLUSION: Positive surgical margins and local disease recurrence were common after resection of NSCLC invading the chest wall. The primary pattern of failure was local recurrence in the chest wall. Adjuvant RT was not associated with improved local control or survival.

Radiation Therapy for Cutaneous T-Cell Lymphomas.

Radiation therapy is an extraordinarily effective skin-directed therapy for cutaneous T-cell lymphomas. Lymphocytes are extremely sensitive to radiation and a complete response is generally achieved even with low doses. Radiation therapy has several important roles in the management of mycosis fungoides. For the rare patient with unilesional disease, radiation therapy alone is potentially curative. For patients with more advanced cutaneous disease, radiation therapy to local lesions or to the entire skin can effectively palliate symptomatic disease and provide local disease control. Compared with other skin-directed therapies, radiation therapy is particularly advantageous because it can effectively penetrate and treat thicker plaques and tumors.

Are discordant positron emission tomography and pathological assessments of the mediastinum in non-small cell lung cancer significant?

OBJECTIVE: Many patients with non-small cell lung cancer have positive mediastinal lymph nodes on preoperative positron emission tomography (PET) but do not have mediastinal involvement after surgery. The prognostic significance of this discordance was assessed. METHODS: This Institutional Review Board-approved study evaluated patients treated with upfront surgery at Duke Cancer Institute (Durham, NC) for non-small cell lung cancer from 1995 to 2008. Those staged with PET with pN0-1 disease after negative invasive mediastinal assessment were included. Mediastinal lymph nodes were scored as positive or negative based on visual analysis of the preoperative PET. Clinical outcomes of the PET-positive and PET-negative cohorts were estimated using the Kaplan-Meier method and compared using a log-rank test. Prognostic factors were assessed using a multivariate analysis. RESULTS: A total of 547 patients were assessed, of whom 105 (19%) were PET positive in the mediastinum. The median number of mediastinal lymph node stations sampled was 4 (range, 1-9). The 5-year risk of local recurrence was 26% in PET-positive versus 21% in PET-negative patients (P = .50). Patterns of local failure were similar between the 2 groups. Distant recurrence (35% vs 29%; P = .63) and overall survival (44% vs 54%; P = .52) were comparable for PET-positive and PET-negative patients. On multivariate analysis, a positive PET was not significant for local recurrence (hazard ratio [HR], 1; P = 1), distant recurrence (HR, 0.82; P = .42), or overall survival (HR, 1.08; P = .62). CONCLUSIONS: Patients with positive mediastinal lymph nodes on preoperative PET, but negative on histologic analysis, are not at increased risk of disease recurrence. Pathologic staging remains the standard.

Outcomes of prosthetic hemodialysis grafts after deployment of bare metal versus covered stents at the venous anastomosis.

PURPOSE: To compare postintervention patency rates after deployment of bare metal versus covered stents across the venous anastomosis of prosthetic arteriovenous (AV) grafts. METHODS: Review of our procedural database over a 6 year period revealed 377 procedures involving stent deployment in an AV access circuit. After applying strict inclusion criteria, our study group consisted of 61 stent deployments in 58 patients (median age 58 years, 25 men, 33 women) across the venous anastomosis of an upper extremity AV graft circuit that had never been previously stented. Both patent and thrombosed AV access circuits were retrospectively analyzed. Within the bare metal stent group, 20 of 32 AV grafts were thrombosed at initial presentation compared to 18 of 29 AV grafts in the covered stent group. RESULTS: Thirty-two bare metal stents and 29 covered stents were deployed across the venous anastomosis. The 3, 6, and 12 months primary access patency rates for bare metal stents were not significantly different than for covered stents: 50, 41, and 22 % compared to 59, 52, and 29 %, respectively (p = 0.21). The secondary patency rates were also not significantly different: 78, 78, and 68 % for bare metal stents compared to 76, 69, and 61 % for covered stents, respectively (p = 0.85). However, covered stents demonstrated a higher primary stent patency rate than bare metal stents: 100, 85, and 70 % compared to 75, 67, and 49 % at 3, 6, and 12 months (p < 0.01). CONCLUSION: The primary and secondary access patency rates after deployment of bare metal versus covered stents at the venous anastomosis were not significantly different. However, bare metal stents developed in-stent stenoses significantly sooner.

Effect of Statins on Serum Prostate-specific Antigen Levels.

OBJECTIVES: The use of statins, which are cholesterol-lowering drugs, has increased significantly during the last decade. In this study, we investigate the effect of statins on serum prostate-specific antigen (PSA) levels in men participating in a prostate cancer screening event. METHODS: A cohort of 4903 men who participated in Prostate Cancer Awareness Week in the years 2007 or 2008 were enrolled in this study from multiple clinical institutions. Within this cohort 1379 men (28.2%) were on a statin medication. Serum PSA, total testosterone, and total cholesterol were compared between the cohort of men using statins and the cohort of men who did not indicate current statin use. In multivariate regression analysis we controlled for age, body mass index (BMI), and race. RESULTS: The mean age of the population was 60.7 years. Serum testosterone levels in patients on statin medication were significantly lower than in patients not on statins (P < .001). Mean total cholesterol levels were similar between the 2 groups (P = .229). Mean serum PSA level was 1.56 ng/mL in patients on statin medication and 1.48 ng/mL in patients not on statin (P = .120). After adjusting for significant covariates (age, BMI, and race), statin use was shown to have a significant association with lower mean PSA (P = .008) and lower mean testosterone (P < .001) and similar total cholesterol (P = .083). CONCLUSIONS: Although use of statins may lower serum PSA levels, its clinical impact is limited. It may not be necessary to determine a different PSA cutoff level for patients on statin medication.