Non-cancer Deaths Research Articles

Use of speckle tracking in the evaluation of late subclinical myocardial damage in survivors of childhood acute leukaemia.

Heart disease is the leading cause of non-cancer death in childhood cancer survivors. to determine the prevalence of subclinical cardiac dysfunction using speckle tracking and compare its results with those obtained by classical methods of assessing left ventricular function and its relationship with different factors to identify the population at higher risk. Echocardiographic assessment of left ventricular function included ejection fraction, tissue Doppler, longitudinal/circumferential strains and biochemical parameters (troponin-T and Pro-BNP) in a cohort of 57 survivors of childhood acute leukaemia with at least 10years since diagnosis. Ventricular dysfunction was found in 5.2% of patients in M-mode (ejection fraction-EF < 53% with a reduction in the EF ≥ 10%) and in 7% of patients with Simpson's method, compared with 21.05 and 8.8% with suboptimal global longitudinal strain (GLS) and global circumferential strain, respectively. The GLS alteration was significantly correlated with lower values of left ventricular systolic function and was associated with high tumour risk (odds ratio [OR] 13.8), cumulative doses of anthracyclines ≥ 250mg/m2 (OR 7.6) and radiotherapy (OR 7.19). Biomarkers were not useful for the diagnosis of subclinical cardiomyopathy. Good reproducibility was obtained, with an intraobserver correlation of 93.6% and an interobserver correlation of 89.2% in the GLS. The alteration of the GLS was more prevalent than the alteration in the EF and was associated with the treatment received and high tumour risk. strain imaging seems to be a powerful tool to identify an increased number of survivor with an early myocardial injury.

PD51-08 ACTIVE SURVEILLANCE OF SPORADIC RENAL MASSES: EXPERIENCE FROM A SINGLE TERTIARY CENTRE

You have accessJournal of UrologyKidney Cancer: Localized: Active Surveillance1 Apr 2018PD51-08 ACTIVE SURVEILLANCE OF SPORADIC RENAL MASSES: EXPERIENCE FROM A SINGLE TERTIARY CENTRE Joana B Neves, James Parker, Chandran Tanabalan, Lee Grant, Navin Ramachandran, Prasad Patki, Faiz Mumtaz, Michael Aitchison, Ravi Barod, and Maxine GB Tran Joana B NevesJoana B Neves More articles by this author , James ParkerJames Parker More articles by this author , Chandran TanabalanChandran Tanabalan More articles by this author , Lee GrantLee Grant More articles by this author , Navin RamachandranNavin Ramachandran More articles by this author , Prasad PatkiPrasad Patki More articles by this author , Faiz MumtazFaiz Mumtaz More articles by this author , Michael AitchisonMichael Aitchison More articles by this author , Ravi BarodRavi Barod More articles by this author , and Maxine GB TranMaxine GB Tran More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2348AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We aim to report on the natural history of renal lesions under active surveillance at a tertiary high-volume referral centre in the UK. METHODS Retrospective analysis of cases with suspected renal cell carcinoma (RCC) at diagnosis under active surveillance from 2012 to 2017. Patients with confirmed hereditary syndromes were excluded. RESULTS 286 patients (180 (62.9%) male, median age at diagnosis 71 (IQR 18)) with 350 lesions were reviewed. The median lesion size was 24.5mm (IQR 20), with 291 (83.1%) lesions under 4cm (small renal mass, SRM) and 17 (4.6%) above 7cm. 56 lesions (48 SRM) were excluded due to lack of follow-up imaging at date of analysis. The median follow-up was 12 months (IQR 20). In 135 lesions (45.9%), histology was known: 73 were RCC, 40 oncocytomas, 9 oncocytic, 10 angiomyolipomas, 2 papillary adenomas, and 1 angiofibroma. During follow-up, 156 (53.1%) lesions remained stable, 21 (7.1%) reduced size and 117 (39.8%) increased in size. Increasing lesions grew a median of 4mm/year (IQR 6.6). Focusing on SRM, the median growth was 2.6mm/year (IQR 4.2), and 16 (6.6%) went over the 4cm threshold. 31 (10.8%) patients changed management after a period of surveillance (17 had surgery, and 14 percutaneous cryoablation). One patient developed metastasis (cT1b clear cell RCC on a patient unfit for intervention). No cancer specific deaths occurred during follow up, but there were 10 non-cancer specific deaths. Limitations of this analysis include the retrospective nature, the lack of central radiological review, and the short follow up period. CONCLUSIONS While our SRM median yearly growth rate is comparable to previous reports, a higher proportion of cases breached the 4cm threshold. Notwithstanding, metastasis-free and cancer-specific survival were close to 100%. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e978 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Joana B Neves More articles by this author James Parker More articles by this author Chandran Tanabalan More articles by this author Lee Grant More articles by this author Navin Ramachandran More articles by this author Prasad Patki More articles by this author Faiz Mumtaz More articles by this author Michael Aitchison More articles by this author Ravi Barod More articles by this author Maxine GB Tran More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

TPF Induction Chemotherapy Prior to Chemoradiation for Locally Advanced Nasopharyngeal Carcinoma

Platinum-based chemoradiation (CRT) with or without adjuvant chemotherapy is considered standard treatment for locally advanced nasopharyngeal carcinoma (LA NPC). Recently, a large randomized trial reported overall survival benefit with TPF induction chemotherapy (IC) prior to CRT compared to CRT alone. We have used TPF IC prior to CRT selectively in patients (pts) with symptomatic LA NPC and report our outcomes with this approach. Eligible pts were retrospectively identified from electronic records, had a pathological diagnosis of stage III-IVB NPC, and received TPF IC at our large academic institution. TPF consisted of docetaxel 75 mg/m2 and cisplatin 100 mg/m2 IV day 1 plus 5-FU 1000 mg/m2/d x 96 hours by IV infusion q21days x 3 cycles given with antibiotic prophylaxis or G-CSF. Radiation entailed 70 Gy in 35 daily fractions using IMRT with lower doses to elective regions. Data were extracted and time-to-event outcomes reported using the Kaplan-Meier method. Of 2997 pts seen in our Head & Neck MDT clinic 2009-2016, 51 (1.7%) had NPC. Thirteen eligible LA NPC pts were identified (25.5%); median age 55 (range: 17-61), stage III/IVA/IVB (23%/69%/8%), 11 were male. Median follow-up was 26 months. Nine pts received TPF to relieve symptoms: cranial neuropathy +/- headache (5 pts), trismus (2 pts), bradycardia (1 pt), and orthopnea (1 pt). Two pts were treated to reduce RT dose to brain stem/optic chiasm, and 2 pts at the oncologist’s discretion. All except 3 pts received 3 TPF cycles. Two pts received only 1 TPF cycle; 1 pt died of cardiac arrest and the other elected to discontinue all treatment with subsequent death due to uncontrolled NPC. One pt did not complete the 3rd cycle due to hearing loss. Eleven pts (85%) experienced at least grade 3 toxicity during TPF with volume depletion, nausea/vomiting, and infection being most common. Prior to CRT the objective partial response rate to TPF was 92.3%. Cancer symptoms improved in all pts. Four pts have died: 1 toxic death, 1 non-cancer death, and 2 due to uncontrolled NPC. Progression-free and overall survival at 3 years were 58% and 67%, respectively. Grade 3 late toxicity has been reported in 4 pts (hearing loss, dental caries, and weight loss). TPF induction chemotherapy prior to CRT was highly active in symptomatic LA NPC pts and induced tumor and symptom remission prior to CRT. Consistent with prior reports, TPF was associated with significant adverse effects in most pts and 1 toxic death, and it should be used by experienced clinicians in suitable pts. Our data support use of TPF IC prior to CRT as a treatment strategy in pts with advanced symptomatic NPC to provide symptom relief prior to CRT, allow more effective delivery of systemic chemotherapy, and potentially improve overall survival. Further research to identify both the optimal TPF regimen and the patient subgroups who benefit most is needed.

Competing nomograms help in the selection of elderly patients with colon cancer for adjuvant chemotherapy.

The extent to which ≥ 70year patients with colon cancer benefit from adjuvant chemotherapy in the presence of competing risks remains controversial. 18,937 patients ≥ 70years with high-risk stage II and stage III colon cancer were retrospectively reviewed from SEER database. Propensity score matching (PSM) was used to adjust for potential baseline confounding. The nomograms were developed based on the competing model to describe the individual probability of colon cancer-specific death (CCSD) and non-CCSD. The subpopulation treatment-effect pattern plot (STEPP) was used to estimate the treatment-effect heterogeneity. In the high-risk stage II subgroup, compared to the non-recipients, the hazard ratios (HR) of overall mortality for recipients were 0.83 (P = 0.001). The subdistribution hazard ratio (SHR) of CCSD for receipts was 1.22 (P = 0.021). The SHR of non-CCSD was 0.63 (P < 0.001). In the stage III subgroup, compared to non-recipients, the HR of the overall mortality for the recipients was 0.62 (P < 0.001). The SHR of CCSD was 0.77 (P < 0.001). The SHR of non-CCSD was 0.58 (P < 0.001). The chemotherapy efficacy differed significantly by risk score of non-CCSD (non-CCSD-RS) (P < 0.001). Recipients with high non-CCSD-RS had a rate of CCSD comparative to that of non-recipients (SHR 0.90, P = 0.150) in the stage III subgroup. A survival analysis based on the overall mortality did not correctly interpret the effect of chemotherapy. Adjuvant chemotherapy did not provide an additional benefit to patients with high-risk stage II or patients with stage III at high risk of non-cancer death.

Abstract P6-15-06: SOLTI-0702 CAPRICE: Final results of a phase II study of pegylated liposomal doxorubicin plus cyclophosphamide followed by paclitaxel as neoadjuvant chemotherapy in elderly or cardiotoxicity-prone patients with high-risk breast cancer: 5-year overall survival disease free survival and late cardiac safety

Abstract Background: Anthracycline and taxane-based chemotherapy is the standard treatment for high-risk breast cancer. However, conventional anthracyclines are not commonly used in elderly patients or those patients prone to cardiotoxicity and there is a potential risk leaving them undertreated. Pegylated liposomal doxorubicin (PLD) has comparable efficacy, but significantly less cardiotoxicity than conventional anthracyclines. We conducted a phase II trial to assess the efficacy and safety of a neoadjuvant chemotherapy (NC) based on PLD and paclitaxel (PTX) in this group of patients. The pathological complete response, breast conservative surgery (BCS) and safety data at a 35-month follow-up were published (Gil-Gil et al. Breast Cancer Res Treat 2015). Here we present the final analysis of 5-year overall survival (OS) and 5-year disease-free survival (DFS) and cardiac safety after 60 months of follow-up. Methods: Fifty patients with stage II (48%) and III (52%) breast cancer (seven cases were T4d) and with at least one risk factor for developing cardiotoxicity were included. NC schedule: PLD 35 mg/m2 plus cyclophosphamide 600 mg/m2 every 4 weeks for four cycles, followed by 80 mg/m2 weekly PTX for 12. Median age was 73 years old (84% were older than 65 years). Forty-eight (96%) of tumors were triple negative (TN). Secondary objectives included 5-year DFS, 5year OS and cardiac safety measured by a decrease in left ventricular ejection fraction (LVEF), electrocardiogram (ECG) anda cardiac questionnaire performed every 3 months during the first year, every 6 months year 2-3 and every 12 months year 4-5 of follow-up. Results: Forty-eight patients (96%) completed the 4 cycles of PLD plus CPM, while only 26 patients (52%) could complete the 12 weeks of PTX. Forty-six patients (92%) underwent surgery. After surgery: 27 patients received radiotherapy, 2 letrozole and 1 trastuzumab. The 5-year OS was 56% (95% CI 41.2-68.4) and the 5-year DFS was 54.4% [95% CI: 38.3-67.9].No significant decrease in LVEF was seen (mean baseline LVEF was 66.6 (52-86) and mean LVEF after 60 months was 66 (54.5-73). Four patients (8%) developed cardiotoxicity (in 2 cases G3). There were 5 non-cancer deaths (10%): 3 during treatment (all in patients &amp;gt; 80 years: a sudden death one month after surgery, a haemorrhagic stroke 30 days after completing chemotherapy and a non-neutropenic pneumonia); and 2 during follow-up (1 Amyotrophic Lateral Sclerosis and 1 intestinal ischemia). Conclusions: PLD followed by PTX as NC was feasible in a fragile population of patients who were not candidates for conventional doxorubicin. The 5 year DFS and 5 year OS in elderly patients with bulky TN tumors were similar tothe reported in the literature. This regimen could be an option for the neoadjuvant treatment of cardiotoxicity-prone patients or elderly patients who present high-risk breast cancer. Citation Format: Gil-Gil M, Bellet M, Morales S, Barnadas A, Manso L, Morilla Ruiz I, Azaro A, Ciruelos Gil E, Garcia Martínez E, Marínez N, Melé M, Soler T, Villagrasa P, Pernas S. SOLTI-0702 CAPRICE: Final results of a phase II study of pegylated liposomal doxorubicin plus cyclophosphamide followed by paclitaxel as neoadjuvant chemotherapy in elderly or cardiotoxicity-prone patients with high-risk breast cancer: 5-year overall survival disease free survival and late cardiac safety [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-15-06.

Early Competing Deaths in Locally Advanced Head-and-Neck Cancer.

Introduction:The competing (noncancer) deaths have increased with aggressive treatment approach and better disease control in locally advanced head-and-neck cancer.Aim:The aim of this study is to find incidence, cause and predictors of early competing mortality in locally advanced head-and-neck cancer patients undergoing combined modality therapy.Subjects and Methods:In this retrospective study, a total of 125 locally advanced head-and-neck patients treated from January 2013 to June 2017 were analyzed. The total number of deaths, cause, and the time of death from the start of therapy was recorded. To study the risk factors of competing deaths, univariate and multivariate logistic regression was applied. Data were analyzed using SPSS v. 24 software.Results:A total of 51 deaths (31 cancer deaths and 20 competing deaths) recorded at a median follow-up of 16 months (1–62 months). The incidence of early competing mortality was 12% (n = 15) with a median time of 2.7 months from treatment initiation. Sepsis was major cause of early competing death (n = 13). On univariate and multivariate logistic regression analysis, competing death was significantly associated with pharyngeal (oropharynx, hypopharynx, and larynx) site primary (odds ratio [OR] = 3.562; 95% confidential interval [CI] = 1.207–10.517; P = 0.016), and Stage IVA/IVB disease (OR = 5.104; 95% CI = 1.123–23.202; P = 0.021).Conclusion:Competing deaths is one of the multifaceted problems in locally advanced head-and-neck cancer patients. Sepsis being single most cause of early competing deaths in Stage IVA/IVB pharyngeal and laryngeal cancer.

Stress Echocardiography Positivity Predicts Cancer Death.

BackgroundStress echocardiography (SE) predicts cardiac death, but an increasing share of cardiac patients eventually die of cancer. The aim of the study was to assess whether SE positivity predicts cancer death.Methods and ResultsIn a retrospective analysis of prospectively acquired single‐center, observational data, we evaluated 4673 consecutive patients who underwent SE from 1983 to 2009. All patients were cancer‐free at index SE and were followed up for a median of 131 months (interquartile range 134). We separately analyzed predetermined end points: cardiovascular, cancer, and noncardiovascular, noncancer death, with and without competing risk. SE was positive in 1757 and negative in 2916 patients; 869 cardiovascular, 418 cancer, and 625 noncardiovascular, noncancer deaths were registered. The 25‐year mortality was higher in SE‐positive than in SE‐negative patients, considering cardiovascular (40% versus 31%; P<0.001) and cancer mortality (26% versus 17%; P<0.01). SE positivity was a strong predictor of cancer (cause‐specific hazard ratio 1.19; 95% confidence interval, 1.16–1.73; P=0.05) and cardiovascular mortality (1.18; 95% confidence interval, 1.03–1.35; P=0.02). Fine–Gray analysis to account for competing risk gave similar results. Cancer risk diverged after 15 years, whereas differences were already significant at 5 years for cardiovascular risk.Conclusions SE results predict cardiovascular and cancer mortality. SE may act as a proxy of the shared risk factor milieu for cancer or cardiovascular death.

The Association of Severe Hypoglycemia With Incident Cardiovascular Events and Mortality in Adults With Type 2 Diabetes.

OBJECTIVEThere is suggestive evidence linking hypoglycemia with cardiovascular disease, but few data have been collected in a community-based setting. Information is lacking on individual cardiovascular outcomes and cause-specific mortality.RESEARCH DESIGN AND METHODSWe conducted a prospective cohort analysis of 1,209 participants with diagnosed diabetes from the Atherosclerosis Risk in Communities (ARIC) study (analytic baseline, 1996–1998). Severe hypoglycemic episodes were identified using first position ICD-9 codes from hospitalizations, emergency department visits, and ambulance calls through 2013. Cardiovascular events and deaths were captured through 2013. We used adjusted Cox regression models with hypoglycemia as a time-varying exposure.RESULTSThere were 195 participants with at least one severe hypoglycemic episode during a median fellow-up of 15.3 years. After severe hypoglycemia, the 3-year cumulative incidence of coronary heart disease was 10.8% and of mortality was 28.3%. After adjustment, severe hypoglycemia was associated with coronary heart disease (hazard ratio [HR] 2.02, 95% CI 1.27–3.20), all-cause mortality (HR 1.73, 95% CI 1.38–2.17), cardiovascular mortality (HR 1.64, 95% CI 1.15–2.34), and cancer mortality (HR 2.49, 95% CI 1.46–4.24). Hypoglycemia was not associated with stroke, heart failure, atrial fibrillation, or noncardiovascular and noncancer death. Results were robust within subgroups defined by age, sex, race, diabetes duration, and baseline cardiovascular risk.CONCLUSIONSSevere hypoglycemia is clearly indicative of declining health and is a potent marker of high absolute risk of cardiovascular events and mortality.

Surgical vs Endoscopic Management of T1 Esophageal Adenocarcinoma: A Modeling Decision Analysis

Although treatment of T1a esophageal adenocarcinoma (EAC) is shifting from esophagectomy to endoscopic therapy, T1b EACs are considered too high risk to be treated endoscopically. We investigated the effectiveness and cost effectiveness of esophagectomy vs endoscopic therapy for T1a and T1b EACs, and the effects of age and comorbidities, using a decision analytic Markov model. We developed a model to simulate a hypothetical cohort of men 75 years old with Charlson comorbidity index scores of 0 and either T1aN0M0 or T1bN0M0 EAC, as a base case. We used the model to compare the effects of esophagectomy vs serial endoscopic therapy. We performed sensitivity analyses based on age at diagnosis of 60-85 years, comorbidity indices of 0-2, andutilities. Post-procedure cancer-specific mortality was derived from the Surveillance, Epidemiology, and End Results Medicare database. In the T1a base case, esophagectomy yielded more unadjusted life years than endoscopic therapy (6.97 vs 6.81), but fewer quality-adjusted life years (QALYs, 4.95 for esophagectomy vs 5.22 for endoscopic therapy). In the T1b base case, esophagectomy yielded more unadjusted life years than endoscopic therapy (5.73 vs 5.01) and QALYs (4.07 vs 3.85 for endoscopic therapy), but was not cost effective (incremental cost-effectiveness ratio $156,981). Sensitivity analysesshowed endoscopic therapy optimized QALYs for patients more than 80years old with a comorbidity index of 1 or 2, or if the ratio of post-esophagectomy to post-endoscopic therapy utilities was below 0.875. In a Markov model, we showed that endoscopic therapy of T1a EAC yields more QALYs and is more cost effective than esophagectomy for patients of all ages and comorbidity indices tested. In contrast, selection of therapy for T1b EAC depends on age and comorbidities, due to surgical mortality and the competing risk of non-cancer death.

The Optimal Management of Postoperative Radiation Therapy in Elderly Patients With Stage I Endometrial Cancer—A National Database Retrospective Analysis

Endometrial cancer is a common malignant tumor of female. Due to the lack of data from large-scale prospective clinical trials, the optimal management of postoperative radiotherapy in elderly patients with stage I endometrial cancer is still unclear. According to current guidelines, postoperative brachytherapy ± pelvic radiotherapy are recommended for elderly patients. However, for elderly patients, competing risks of noncancer death and other morbid events affect radiation treatment decisions since age can influence the efficacy of treatment. This study aimed at analyzing corresponding clinical and pathological features to assess the best mode of postoperative radiotherapy. A retrospective review was conducted in patients with stage I endometrial cancer, who underwent radical surgery and postoperative radiotherapy in the National Cancer Institute's SEER database from January 2007 to December 2013. Patients who were over 65 years old and had accurate pathologic findings and complete follow-up data were enrolled. Patients were divided into pelvic irradiation ±brachytherapy and brachytherapy only. The patients were divided into low risk group (IA stage, well differentiated), intermediate to low risk(IA, poorly-moderate differentiated ) ,intermediate risk(IB, moderate-high differentiated), intermediate to high risk group (IB stage, poorly differentiated). Kaplan-Meier method was used for survival analysis. Cox regression model was used for multivariate analysis. A total of 2280 eligible patients were included in the analysis, 839 of whom received pelvic irradiation ± brachytherapy, and 1441 patients received simple brachytherapy. After a median follow-up of 33 months (range: 1-83 months), 163 patients died (93 patients in the pelvic irradiation group and 70 patients in the brachytherapy group). 3-year overall survival was 88.9% and 94.9% in pelvic irradiation and brachytherapy group, respectively. Subgroup analysis suggested that for elderly patients in low-risk, intermediate risk and intermediate to high risk groups, the diffencce in radiotherapy management didn’t affect overall survival (p = 0.27, 0.06, 0.29,respectively). However, for patients with low to intermediate risk, the survival rate of the brachytherapy alone was superior to that of the pelvic irradiation ± brachytherapy ( p= 0.00). Multivariate COX regression analysis suggested that the mode of radiotherapy and the degree of differentiation were independent prognostic factors (HR = 1.87, 95% CI 1.37-2.57, p = 0.00; HR = 0.28, 95% CI 0.16-0.51, p= 0.00,respectively). For elderly patients with stage I endometrial cancer, the effect of brachytherapy alone is similar to that of pelvic irradiation± brachytherapy. For patients with low to intermediate risk, brachytherapy alone is even better. Therefore, considering different risk factors, brachytherapy alone may be the most cost effective choice for postoperative radiotherapy.

SBRT for Central Tumors in Early Stage NSCLC Patients

For NSCLC patients treated with SBRT, we investigated if proximity to the proximal bronchial tree is associated with non-cancer death. From 2006-2013 patients with a single early stage NSCLC tumors were irradiated with CBCT guided SBRT (median dose 54 Gy in 3 fractions) in 5 institutes. Patients with progressive disease, metastases, or second cancers at the time of death were scored as death from cancer; all other deceased patients were scored as non-cancer death. Treatment plans were collected, and the main and lobar bronchi were automatically delineated using atlas based segmentation. For each patient the shortest distance from the edge of the GTV to the proximal bronchial tree (PBT) was determined. Patients were stratified into 3 groups; GTV≥2 cm from the PBT (peripheral (A); RTOG 0236), GTV ≥1 cm and < 2 cm from the PBT (B), and GTV <1 cm from the PBT (C). Actuarial non-cancer survival at 1y, 2y and 5y were determined (i.e., death from cancer was censored). Association between the stratified distance of the GTV to the PBT and non-cancer death were evaluated using univariate Cox regression (at the P<0.05 level), and compared to the association with cause specific survival to test for competing mortality risk. Finally, the stratified distance was included in a multivariate Cox analysis, also including; age, gender, performance status, comorbidity index, lung-function FEV1, Mean Lung Dose, tumor diameter, and smoking history. Seven hundred sixty-nine patients were identified with a median age of 75 y. Median Biologically Equivalent Dose (a/b = 10 Gy) was 126 Gy, 180 Gy and 227 Gy for group C, B, and A, respectively, with 33, 71 and 665 patients per group. Median GTV diameter was 4.1 cm (1.1-7.0), 2.7 cm (0.9-5.7) and 2.2 cm (0.7-6.5) for groups C, B, and A, respectively. Survival rates were lower for patients in group C (Table 1) with a Hazard ratio (HR) of 2.91 (P < 0.001). Patients in group B had a lower, non-significant HR of 0.87 (P = 0.554). The association with cause specific survival showed a significantly higher HR (2.45, P = 0.036) for patients in group C with respect to A, but not B. In the multivariate Cox analysis, the stratified distance from the GTV to PBT was significantly associated with non-cancer death (group C: P<0.001, HR = 3.56, group B: P = 0.319, HR = 0.79), as well as age (P = 0.001, HR = 1.03), performance status (P<0.001, HR = 0.30) and lung-function FEV1 (P = 0.004, HR = 0.99). Patients with a tumor < 1 cm from the proximal bronchial tree had 3.56 fold higher risk of non-cancer death than patients with a peripheral tumor. Delivered dose distributions will be further studied.Tabled 1Abstract 35; Table 1 Actuarial survival for non-cancer death for (A) GTV≥2 cm from the PBT (peripheral; RTOG 0236), (B) GTV ≥1 cm and < 2 cm from the PBT, and (C) GTV <1 cm from the PBTTotal (#)1 year survival (%)2 year survival (%)5 year survival (%)A: GTV ≥ 2 cm665917748B: GTV ≥ 1 cm and < 2 cm71917658C: GTVs < 1cm33773814 Open table in a new tab

Use of frailty to predict survival in elderly patients with early stage non-small-cell lung cancer treated with stereotactic body radiation therapy.

Frailty has been shown to increase morbidity and mortality independent of age, but studies are lacking in radiation oncology. This study evaluates a modified frailty index (mFI) in predicting overall survival (OS) and non-cancer death for Stage I/II [N0M0] Non-Small-Cell Lung Cancer (NSCLC) patients treated with Stereotactic Body Radiation Therapy (SBRT). Medical records for all patients with Stage I/II NSCLC treated at our institution with SBRT from 2009 to 2014 were reviewed. A validated mFI score, consisting of 11 variables was calculated, classifying patients as non-frail (0-1) or frail (≥2). Primary endpoint (OS) was analyzed using Kaplan-Meier method and log-rank. Secondary endpoint, non-cancer death, was analyzed using Fine-Gray's method, with death from lung cancer as a competing risk. Patient cohort consisted of 38 (27.3%) non-frail and 101 (72.7%) frail [median total mFI score 3.0 (range 0-7)]. Median age and pack-year history was 74 and 46years, respectively. Median follow-up among survivors was 38.5months (range 4.0-74.1months). Frailty was associated with a lower 3-year OS (37.3% vs. 74.7%; p=0.003) and 3-year cumulative incidence of non-cancer death (36.7% vs. 12.5%; p=0.02). Frailty remained significant in the multivariate model [OS HR for mFI ≥2: 2.25 (1.14-4.44); p=0.02]. Frailty is associated with lower OS in older patients with early stage NSCLC treated with SBRT, yet frail patients survived a median 2.5years, and were more likely to die of causes unrelated to the primary lung cancer, suggesting SBRT should be considered even in older patients deemed unfit for surgery.

Outcomes of men on active surveillance for low-risk prostate cancer at a safety-net hospital

PurposeTo characterize demographic, disease, and cancer outcomes of men on active surveillance (AS) at a safety-net hospital and characterize those who were lost to follow-up (LTFU). MethodsFrom January 2004 to November 2014, 104 men with low-risk prostate cancer (PCa) were followed with AS at Zuckerberg San Francisco General Hospital (ZSFG). Criteria for AS have evolved over time; however, patients with diagnostic prostate-specific antigen (PSA) 10ng/mL or less, clinical stage T1/2, biopsy Gleason score 3 + 3 or 3 + 4, 33% or fewer positive cores, and 50% or less tumor in any single core were potentially eligible for AS. Men were longitudinally followed with a PSA or digital rectal examination or both every 3 to 6 months, and repeat prostate biopsy every 1 to 2 years. Clinical staging and grading were based on a physical examination and at least a 12-core biopsy, respectively. LTFU was defined as failure to successfully contact patients with 3 phone calls or any urology visit recorded within 18 months from a prior visit or biopsy. A secondary chart review was performed using the electronic medical record at ZSFG as well as EPIC Systems CareEverywhere which allows access to select non-ZSFG institutions to confirm that patients were truly LTFU. ResultsAmong the 104 men on AS at ZSFG, the median age at diagnosis of PCa was 61.5 years (range: 44–81). The median follow-up period was 29 months (range: 0–186 months) during which 18 (17.3%) men were LTFU and 48 (46%) remained on surveillance. Men underwent a median of 7 (1–21) serum PSA measurements and an average of 2 prostate biopsies (1–5). In total, 22 (20.6%) men had definitive treatment with the median time from diagnosis to active treatment being 26 (range: 2–87) months. Radiation therapy was more common than radical prostatectomy (12.5% vs. 7.7%). There was 1 PCa–related death and 3 noncancer deaths. Initial adherence to AS was poor; however, men committed to AS initially were ultimately more compliant over time. ConclusionAS for low-risk PCa is challenging among a vulnerable population receiving care in a safety-net hospital, as rates of LTFU were high. Our findings suggest the need for AS support programs to improve adherence and follow-up among vulnerable and underserved populations.

Physical Activity and Lifetime Risk of Cardiovascular Disease and Cancer.

Although the World Health Organization has recommended moderate- to vigorous-intensity physical activity (MVPA) to prevent cardiovascular disease (CVD) and some cancers, there are no estimates of lifetime risk of these noncommunicable diseases according to PA levels. We aimed to estimate the lifetime risk of CVD and cancers according to PA levels. We followed 5807 men and 7252 women in the United States, 45-64 yr old, initially free of CVD and cancer from 1987 through 2012, and used a life table approach to estimate lifetime risks of CVD (coronary heart disease, heart failure, and stroke) and total cancer according to PA levels: poor (0 min·wk of MVPA), intermediate (1-74 min·wk of VPA or 1-149 min·wk of MVPA), or recommended (≥75 min·wk of VPA or ≥150 min·wk of MVPA). During the 246,886 person-years of follow-up, we documented 4065 CVD and 3509 cancer events and 2062 non-CVD and 2326 noncancer deaths. In men, the lifetime risks of CVD from 45 through 85 yr were 52.7% (95% confidence interval = 49.4-55.5) for poor PA and 45.7% (42.7-48.3) for recommended PA. In women, the respective lifetime risks of CVD were 42.4% (39.5-44.9) and 30.5% (27.5-33.1). Lifetime risks of total cancer were 40.1% (36.9-42.7) for poor PA and 42.6% (39.7-45.2) for recommended activity in men and 31.4% (28.7-33.8) and 30.4% (27.7-32.9), respectively, in women. Compared with a poor PA level, the PA recommended by the World Health Organization was associated with lower lifetime risk of CVD, but not total cancer, in both men and women.

Type 2 diabetes, adiposity and cancer morbidity and mortality risk taking into account competing risk of noncancer deaths in a prospective cohort setting.

Type 2 diabetes (T2D) and adiposity associate with increased risk of several cancers, but the impact of competing risk of noncancer deaths on these associations is not known. We prospectively examined participants in the Malmö Diet and Cancer Study aged 44–73 years with no history of cancer at baseline (n = 26,953, 43% men). T2D was ascertained at baseline and during follow‐up, and body mass index (BMI) and waist circumference (WC) at baseline. Multivariable cause‐specific hazard ratios (HR) and subdistribution hazard ratios (sHR), taking into account noncancer deaths, were estimated using Cox‐ and competing risk regression. During follow‐up (mean 17 years), 7,061 incident cancers (3,220 obesity‐related cancer types) and 2,848 cancer deaths occurred. BMI and WC were associated with increased risk of obesity‐related cancer incidence and cancer mortality. In T2D subjects, risk of obesity‐related cancer was elevated among men (HR = 1.31, 95% CI: 1.12–1.54; sHR = 1.29, 95% CI: 1.10–1.52), and cancer mortality among both men and women (HR = 1.34, 95% CI: 1.20–1.49; sHR = 1.30, 95% CI: 1.16–1.45). There was no elevated actual risk of cancer death in T2D patients with long disease duration (sHR = 1.00, 95% CI: 0.83–1.20). There was a significant additive effect of T2D and adiposity on risk of obesity‐related cancer and cancer mortality. In conclusion, detection bias may partially explain the increased risk of cancer morbidity among T2D patients. Both excess risk of competing events among patients with T2D and depletion of susceptibles due to earlier cancer detection will lower the actual risk of cancer, particularly with longer diabetes duration and at older ages.

Comorbidity and cause of death after surgery for early stage colorectal cancer (CRC).

e15139 Background: Early stage (I/II) CRC is traditionally associated with relatively good prognosis at 90% relative survival. The probability of non-cancer death in CRC patients is associated with comorbidity burden; however, there is paucity of data evaluating this association in colon versus rectal cancer. This study examines the impact of comorbdity on 5-year mortality and cause of death after resection for early stage CRC. Methods: Linked patient-level data from the New York State Cancer Registry &amp; Statewide Planning and Research Cooperative System was queried for 2004-2013 patients who underwent colectomy or proctectomy for Stage I-II CRC who survived beyond 30 days. Comorbidity burden was defined as the sum of Elixhauser Comorbidites plus steroid use, MI history, CVD (cardiovascular disease), and dementia to capture maximum number of unique comorbidities and characterized as low (0-1 comorbidity), moderate (2-3 comorbidities), and high (4+ comorbidities). Causes of death were evaluated according to comorbidity group and colon versus rectal cancer. Results: 24,643 (colon 21,384, rectal 3,250) met inclusion criteria, of which 5,464 (22%) died within 5 years. While both colon cancer (CC) and rectal cancer patients (RC) had identical overall mortality (22%), significant differences existed in the proportion of deaths due to the primary cancer with disease-specific mortality of 7% for CC and 11% for RC. Deaths due to CC decreased while CVD causes increased with escalating comorbidity burden. Deaths due to RC accounted for nearly 50% of all deaths even with increasing comorbidity burden (Table). Conclusions: CC is the predominant cause of 5-year mortality in early stage patients with low comorbidity burden while CVD drives mortality in high comorbidity burden patients. In contrast, RC drives early stage mortality regardless of the comorbidity burden; thus, emphasizing the importance of tailored survivorship programs to each cancer. [Table: see text]

Dose to heart substructures is associated with non-cancer death after SBRT in stage I–II NSCLC patients

Background and purposeTo investigate potential associations between dose to heart (sub)structures and non-cancer death, in early stage non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT). Methods803 patients with early stage NSCLC received SBRT with predominant schedules of 3×18Gy (59%) or 4×12Gy (19%). All patients were registered to an average anatomy, their planned dose deformed accordingly, and dosimetric parameters for heart substructures were obtained. Multivariate Cox regression and a sensitivity analysis were used to identify doses to heart substructures or heart region with a significant association with non-cancer death respectively. ResultsMedian follow-up was 34.8months. Two year Kaplan–Meier overall survival rate was 67%. Of the deceased patients, 26.8% died of cancer. Multivariate analysis showed that the maximum dose on the left atrium (median 6.5Gy EQD2, range=0.009–197, HR=1.005, p-value=0.035), and the dose to 90% of the superior vena cava (median 0.59Gy EQD2, range=0.003–70, HR=1.025, p-value=0.008) were significantly associated with non-cancer death. Sensitivity analysis identified the upper region of the heart (atria+vessels) to be significantly associated with non-cancer death. ConclusionsDoses to mainly the upper region of the heart were significantly associated with non-cancer death. Consequently, dose sparing in particular of the upper region of the heart could potentially improve outcome, and should be further studied.

MP14-02 THE NATURAL HISTORY OF MEN ON ACTIVE SURVEILLANCE WITH LOW-RISK PROSTATE CANCER AT A SAFETY-NET, COUNTY HOSPITAL

You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History II1 Apr 2017MP14-02 THE NATURAL HISTORY OF MEN ON ACTIVE SURVEILLANCE WITH LOW-RISK PROSTATE CANCER AT A SAFETY-NET, COUNTY HOSPITAL E. Charles Osterberg, Nynikka Palmer, Catherine Harris, Gregory Murphy, Sarah Blaschko, Carissa Chu, Matthew Cooperberg, Peter Carroll, and Benjamin Breyer E. Charles OsterbergE. Charles Osterberg More articles by this author , Nynikka PalmerNynikka Palmer More articles by this author , Catherine HarrisCatherine Harris More articles by this author , Gregory MurphyGregory Murphy More articles by this author , Sarah BlaschkoSarah Blaschko More articles by this author , Carissa ChuCarissa Chu More articles by this author , Matthew CooperbergMatthew Cooperberg More articles by this author , Peter CarrollPeter Carroll More articles by this author , and Benjamin BreyerBenjamin Breyer More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.466AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Health care delivery to vulnerable and uninsured patients is challenging due to social and economic barriers. For men with low-risk prostate cancer (PCa) on active surveillance (AS), patient compliance, follow up, and access to care are essential for favorable cancer outcomes. Our primary objective is to characterize demographic, disease and cancer outcomes of men on AS at a safety-net hospital and characterize those who were loss to follow-up (LTFU). METHODS From January 2004 to November 2014, 104 men at Zuckerberg San Francisco General (ZSFG) with low-risk PCa were followed with AS. Criteria for AS has evolved over time; however, patients with diagnostic PSA 10ng/mL or less, clinical stage T1/2, biopsy Gleason grade 3+3 or 3+4, 33% or fewer positive cores and 50% or less tumor in any single core were eligible for AS. Men were longitudinally followed with a PSA and/or DRE every 3-6 months and repeat prostate biopsy every 1-2 years. Clinical staging and grading were based on a physical exam and at least a 12-core biopsy respectively. LTFU was defined as failure to contact patients with three phone calls or any urology visit recorded within 18 months from a prior visit or biopsy. A secondary chart review was performed with EPIC Systems© CareEverywhere which allows access to non-ZSFG institutions to confirm patients were truly LTFU. RESULTS Among the 104 men on AS at ZSFG, the median age at diagnosis of PCa was 61.5 years (range: 44-81). The median follow-up time period was 29 months (0-186 months) during which 18 men were LTFU and 48 remained on surveillance. Men who remained on AS underwent a median of 7 (1-21) serum PSA measurements and an average of 2 prostate biopsies (1-5). In total, 22 (20.6%) men had definitive treatment with the median time from diagnosis to active treatment being 26 (2-87) months. Radiation therapy was more common that radical prostatectomy (12.5% versus 7.7%). There was one prostate cancer-related death and three non-cancer deaths. Kaplan-Meir curve analysis demonstrates that initial adherence to AS is poor; however as time progresses, adherence increases as those patients committed to early surveillance continue with follow-up. CONCLUSIONS AS for low-risk prostate cancer is challenging among a vulnerable population receiving care in a safety-net hospital, as rates of LTFU were high. Our findings suggest the need for an AS program to improve adherence and follow-up among vulnerable and underserved populations. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e162-e163 Advertisement Copyright & Permissions© 2017MetricsAuthor Information E. Charles Osterberg More articles by this author Nynikka Palmer More articles by this author Catherine Harris More articles by this author Gregory Murphy More articles by this author Sarah Blaschko More articles by this author Carissa Chu More articles by this author Matthew Cooperberg More articles by this author Peter Carroll More articles by this author Benjamin Breyer More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP72-12 SURVEILLANCE AFTER SURGERY FOR RENAL CELL CARCINOMA: A RISK-ADAPTED APPROACH

You have accessJournal of UrologyKidney Cancer: Localized: Surgical Therapy V1 Apr 2017MP72-12 SURVEILLANCE AFTER SURGERY FOR RENAL CELL CARCINOMA: A RISK-ADAPTED APPROACH William Parker, Suzanne Merrill, Phillip Schulte, Ross Mason, R. Houston Thompson, Christine Lohse, and Igor Frank William ParkerWilliam Parker More articles by this author , Suzanne MerrillSuzanne Merrill More articles by this author , Phillip SchultePhillip Schulte More articles by this author , Ross MasonRoss Mason More articles by this author , R. Houston ThompsonR. Houston Thompson More articles by this author , Christine LohseChristine Lohse More articles by this author , and Igor FrankIgor Frank More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2248AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The risk of recurrence following surgical excision of clear cell renal cell carcinoma (ccRCC) varies based on clinical and pathologic features, while risk of non-cancer death evolves as a function of age and comorbidities. Despite these differences in how these competing risks mature over time, current guidelines recommend surveillance based on stage alone. We therefore sought to develop risk adapted postoperative surveillance recommendations. METHODS Patients with ccRCC managed surgically between 1990 and 2008 (n=2,511) were identified from the Mayo Clinic Nephrectomy registry and risks of abdominal and chest recurrence estimated using accelerated failure-time (AFT) models by pathology stage (pT1a, pT1b, pT2, pT3/4, or pTanyN+). Similarly, risk of non-cancer death was estimated by age (<50, 51-59, 60-69, 70-79, and ≥80) and comorbidity index (CCI: ≤1 versus >1). Recommended surveillance schedules balance estimated risk of non-cancer death with recurrence risk where allowable recurrence is up to the risk of non-cancer death. Surveillance intervals were calculated based on each 1%, 3%, and 5% recurrence risk increase to a maximum 10 years. Intervals shorter than 3 months were not allowed, with the next risk increase calculated from the date of the adjusted interval. RESULTS AFT models for recurrence and death for stage, age, and comorbidity risk groups were generated (tables). Recommended interval schedules (e.g. 1%, 3%, or 5%) are based on the predicted risk of non-cancer death for a given age and CCI group. For example, patients <70 years with a CCI score ≤1 would be followed on a 1% risk of recurrence schedule for the duration of 10 years of follow-up regardless of stage. Conversely, patients 60-69 years old with a CCI >1, would follow a 1% interval for the first year only, then switch to 3% interval until year 6, at which point they would follow a 5% schedule. CONCLUSIONS Using an AFT model for estimating risk of recurrence and risk of death we were able to generate risk-adapted screening intervals for surgical managed patients with RCC. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e958-e959 Advertisement Copyright & Permissions© 2017MetricsAuthor Information William Parker More articles by this author Suzanne Merrill More articles by this author Phillip Schulte More articles by this author Ross Mason More articles by this author R. Houston Thompson More articles by this author Christine Lohse More articles by this author Igor Frank More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP04-13 CANCER SURVEILLANCE AFTER RADICAL CYSTECTOMY FOR UROTHELIAL CARCINOMA: A NOVEL RISK-ADAPTED STRATEGY

You have accessJournal of UrologyBladder Cancer: Epidemiology & Evaluation I1 Apr 2017MP04-13 CANCER SURVEILLANCE AFTER RADICAL CYSTECTOMY FOR UROTHELIAL CARCINOMA: A NOVEL RISK-ADAPTED STRATEGY Ross Mason, William Parker, Stephen A. Boorjian, Suzanne Merrill, Prabin Thapa, and Igor Frank Ross MasonRoss Mason More articles by this author , William ParkerWilliam Parker More articles by this author , Stephen A. BoorjianStephen A. Boorjian More articles by this author , Suzanne MerrillSuzanne Merrill More articles by this author , Prabin ThapaPrabin Thapa More articles by this author , and Igor FrankIgor Frank More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.151AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Current guidelines for surveillance after radical cystectomy (RC) are based on pathologic stage and do not take into account other patient specific factors. We previously reported Weibull models determining duration of cancer surveillance. We now present a novel surveillance protocol outlining the frequency and duration of follow-up based on stage specific recurrence risk and competing risks of non-cancer mortality. METHODS We identified 2205 patients who underwent RC for urothelial carcinoma (UC) at the Mayo Clinic from 1980 to 2010. The risks of abdomen/pelvis and chest recurrence were estimated using accelerated failure-time (AFT) models, stratified by pathologic stage (pT0, pTa/Cis/1, pT2, pT3/4, pTanyN+). Similarly, the risks of non-cancer death according to age (<60, 60–69, 70–79, >80) and Charlson comorbidity index (CCI <1 versus ≥1) were also calculated. Surveillance intervals were calculated for each conditional 1%, 3%, and 5% recurrence risk increase up to 10 years follow-up. Specific surveillance recommendations balance estimated risk of non-cancer death with recurrence risk where allowable recurrence risk is up to the risk of non-cancer death. RESULTS At a median follow-up of 4.7 years (IQR 1.1, 10.3), disease recurrence was diagnosed in 852 (38.6%) patients. Using AFT models for recurrence, surveillance intervals for all stage, age, and comorbidity risk groups were generated. The surveillance strategy (e.g. 1%, 3%, or 5%) for an individual patient is selected based on probability of non-cancer specific mortality as determined by age and CCI (Tables 1 and 2). For example, a patient less than 60 with CCI ≤ 1 would follow a 1% recurrence risk schedule for the full 10 years. Conversely, a patient age 60-69 with a CCI > 1 would follow a 5% schedule for the full 10 years. CONCLUSIONS Using AFT modeling we have developed a risk-adapted protocol for surveillance frequency and duration after RC taking into account both the risk of recurrence and the risk of non-cancer mortality. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e33 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Ross Mason More articles by this author William Parker More articles by this author Stephen A. Boorjian More articles by this author Suzanne Merrill More articles by this author Prabin Thapa More articles by this author Igor Frank More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...