Non-cancer Causes Research Articles

Evaluation of Surgical Procedures for T2 Gallbladder Cancer in Terms of Recurrence and Prognosis.

T2 (tumor invades perimuscular connective tissue; no extension beyond serosa or into liver) gallbladder cancer has generally been treated by S4aS5 subsegmentectomy (S4aS5 HR). We investigated the therapeutic effect of full-thickness cholecystectomy (FC) and gallbladder bed resection (GBR), in terms of tumor location and resection margin (distance from the tumor). At our department we employ the following protocol to determine the extent of resection needed to achieve R0 status: (1) A tumor located in the gallbladder fundus (Gf) or body (Gb) and only on the free peritoneal side was classified as P-type, for which full-thickness cholecystectomy and regional lymph node dissection were performed. (2) A tumor located in Gf or Gb and in contact with the liver bed was classified as H-type, for which gallbladder bed resection and regional lymph node dissection were performed. (3) A tumor located in the gallbladder neck (Gn) was classified as N-type, for which gallbladder bed resection, bile duct resection, and regional lymph node dissection were performed. Twenty-two patients admitted to our department between January 2000 and December 2014 with pT2gallbladder cancers were included in our study. Surgical procedures performed were compared with those specified in our protocol, and patients in whom the extent of resection was greater than that specified in our strategy were evaluated clinicopathologically and in terms of recurrence and the prognosis. Six (27.2%), 7 (31.8%), and 9 (40.9%) patients underwent limited, standard, and extended surgery, respectively. Ten (66.7%) of 15 patients with tumors close to the liver bed underwent cholecystectomy or extended surgery, 7 (85.7%) of 8 patients with tumors close to the bile duct underwent bile duct resection, and 16 (72.7%) of 22 patients underwent regional lymph node dissection. Recurrence at the bile duct resection margin, para-aortic lymph node metastasis, and hepatic metastasis occurred in 2, 1, and 3 patients, respectively. The 3-year survival rates (for patients including those dying of noncancer causes) were 50, 100, and 75% after limited, standard, and extended surgery, respectively. There was a significant difference in the survival rate of patients who underwent standard or extended surgery (P=0.0273). Favorable results were obtained in T2 gallbladder cancer patients without performing S4aS5 subsegmentectomy. Depending on the tumor location, neither full-thickness cholecystectomy nor gallbladder bed resection appeared to pose problems regarding recurrence or prognosis. In conclusion, surgical treatment based on our protocol, which aims to achieve the condition of R0, may result in a sufficient therapeutic effect.

Resource Use in the Last Year of Life Among Patients Who Died With Versus of Prostate Cancer

BackgroundProstate cancer poses a significant financial burden in the United States. However, most men with prostate cancer will die from noncancer causes. Concerns about increased resource utilization at the end of life have not been appropriately examined in this context. Materials and MethodsWe conducted a retrospective analysis of Surveillance, Epidemiology, and End Results-Medicare data of men who were diagnosed with and died of, as opposed to with, prostate cancer between 2000 and 2007. Within these 2 populations, we compared changes in the use of medical interventions, hospice, and overall health care costs to Medicare in the last year of life. ResultsAmong 34,727 patients, those who died of prostate cancer had lower costs ($43,572 vs. $45,830; P < .001), largely because of lower mean inpatient costs ($20,769 vs. $29,851) and fewer hospitalizations (1.8 vs. 2.1), inpatient days (12.2 vs. 15.7), intensive care unit (ICU) days (1.4 vs. 3.4), and skilled nursing facility days (11.7 vs. 14.7; P < .001 for all). Outpatient and hospice costs were significantly greater among patients who died of prostate cancer, as was use of chemotherapy and androgen deprivation therapy. Patients who died of prostate cancer had approximately 12% lower costs than patients who died from other causes in adjusted analyses (fold-change, 0.88; 95% confidence interval [CI], 0.85-0.92). The single strongest predictor of increased costs at the end of life was receipt of multiple invasive procedures (fold increase in costs, 2.39; 95% CI, 2.22-2.58). ConclusionPatients who died of prostate cancer rather than from other causes had more hospice and outpatient use, less inpatient and ICU use, and lower overall costs. Efforts to shift care toward outpatient settings might provide more efficient and judicious care for patients during the end of life.

P0031 Use of FOLFOX4 regimen in stage IV cervical cancer: A pilot study

Background We performed a phase 2, single arm, open-label study of FOLFOX4 (oxaliplatin/fluorouracil/leucovorin) chemotherapy as palliative treatment in patients with metastatic cervical cancer to assess its efficacy and safety. Methods The patients recruited for this study were 18–65 years old had metastatic cervical cancer, prior radiotherapy treatment, Eastern Cooperative Oncology Group (ECOG) performance status 0–1, life expectancy more than 6 months, adequate haematological, renal, and hepatic functions, and were able to comply with scheduled follow-up and with management of toxicity. Thirty patients were enrolled from December 2011, to January 2012. All patients received FOLFOX4 (oxaiplatin 85 mg/m2 on day 1, fluorouracil 400 mg/m2 intravenous push on day 1–2, fluorouracil 600 mg/m2 intravenous drip in 22 h on day 1–2, and folinic acid 200 mg/m2 intravenous push on day 1–2). Outcomes were treatment response after six and 12 cycles of FOLFOX4, and every 3 months thereafter, according to World Health Organisation (WHO) criteria and Response Evaluation Criteria in Solid Tumours (RECIST) guidelines, and toxicity. Findings The mean age was 51 years (range 24–64), and 80% of patients had squamous cell metastasis from cervical cancer. 70% had metastasis at a distant lymph node. 59% of patients received at least six cycles of FOLFOX4. Nine patients (31%) achieved an objective response. At the mean follow-up time of 12.8 months, 1-year progression-free and overall survival was 20.7% and 65.5%, respectively. The most common grade ⩾ 2 toxicities during chemotherapy were fatigue (48.3%) and anaemia (37.9%). One patient died during the first cycle of FOLFOX4 due to a non-cancer cause. Interpretation FOLFOX4 regimen in metastatic cervical cancer is feasible and of reasonable toxicity.

Comprehensive Echocardiographic Detection of Treatment-Related Cardiac Dysfunction in Adult Survivors of Childhood Cancer: Results From the St. Jude Lifetime Cohort Study

BackgroundTreatment-related cardiac death is the primary, noncancer cause of mortality in adult survivors of childhood malignancies. Early detection of cardiac dysfunction may identify a high-risk subset of survivors for early intervention. ObjectivesThis study sought to determine the prevalence of cardiac dysfunction in adult survivors of childhood malignancies. MethodsEchocardiographic assessment included 3-dimensional (3D) left ventricular ejection fraction (LVEF), global longitudinal and circumferential myocardial strain, and diastolic function, graded per American Society of Echocardiography guidelines in 1,820 adult (median age 31 years; range: 18 to 65 years) survivors of childhood cancer (median time from diagnosis 23 years; range: 10 to 48 years) exposed to anthracycline chemotherapy (n = 1,050), chest-directed radiotherapy (n = 306), or both (n = 464). ResultsOnly 5.8% of survivors had abnormal 3D LVEFs (<50%). However, 32.1% of survivors with normal 3D LVEFs had evidence of cardiac dysfunction by global longitudinal strain (28%), American Society of Echocardiography–graded diastolic assessment (8.7%), or both. Abnormal global longitudinal strain was associated with chest-directed radiotherapy at 1 to 19.9 Gy (rate ratio [RR]: 1.38; 95% confidence interval [CI]: 1.14 to 1.66), 20 to 29.9 Gy (RR: 1.65; 95% CI: 1.31 to 2.08), and >30 Gy (RR: 2.39; 95% CI: 1.79 to 3.18) and anthracycline dose > 300 mg/m2 (RR: 1.72; 95% CI: 1.31 to 2.26). Survivors with metabolic syndrome were twice as likely to have abnormal global longitudinal strain (RR: 1.94; 95% CI: 1.66 to 2.28) and abnormal diastolic function (RR: 1.68; 95% CI: 1.39 to 2.03) but not abnormal 3D LVEFs (RR: 1.07; 95% CI: 0.74 to 1.53). ConclusionsAbnormal global longitudinal strain and diastolic function are more prevalent than reduced 3D LVEF and are associated with treatment exposure. They may identify a subset of survivors at higher risk for poor clinical cardiac outcomes who may benefit from early medical intervention.

Caring for the adult survivor of Hodgkin lymphoma: highlighting the need for care coordination.

Caring for the adult survivor of Hodgkin lymphoma: highlighting the need for care coordination.

Sa2043 Inherent Single Nucleotide Variants in the TBX21 Gene As Novel Prognostic Markers in Patients With Pancreatic Ductal Adenocarcinoma

G A A b st ra ct s metastatic PC patients. SOMAmer® reagents are a unique class of DNA aptamers that bind their protein targets with high selectivity and a median limit of detection of 40fM. We have reported that a plasma SOMApanel can detect resectable PC in a multi-center case-control study. Methods: Chart reviews were performed for the 100 PC patients from our site used in the prior study to determine their time to disease progression (PFS) through September 2014. Pre-treatment plasma samples collected between 2008 and 2010 were analyzed for CA 19-9 and a SOMAscanTM assay consisting of 1045 known proteins. Univariate Cox models were used for identifying biomarkers related to time to progression compared to patients who have not progressed. Short PFS was defined as those with documented progression less than one year from PC diagnosis or unrecognized metastatic disease found at surgery. Long PFS was defined as progression greater than one year. The top 10 proteins identified in this analysis were then compared to 42 Stage IV patients. Statistical p-values were calculated with log likelihood ratio test of Cox regression and corrected for multiple comparisons using q-values calculated with the Benjamin and Hochberg method. Results: Nine of 43 patients who had resection for pancreatic cancer were excluded due to noncancer cause of death in the first year or loss to follow up. Thirty-four patients were eligible for progression analysis: 14 with short PFS including 2 individuals with unrecognized metastatic disease and 7 with no disease progression with a minimum 4 year's follow-up. As shown in the Figure, two of the 10 top performing prognostic proteins that had higher levels correlating with shorter PFS times were present at similar levels in baseline samples from subjects presenting with Stage IV PC. CA 19-9 was not prognostic in these samples. Conclusions: This study demonstrates the potential utility of identifying biomarkers that predict the presence of unrecognized metastatic disease defined as the detection of metastases at or the rapid recurrence following attempted curative resection of a PC. Future studies are planned to validate the results. If successful, this could lead to a test that identifies a subset of PC patients who can avoid the morbidity and health care costs associated with a major pancreatic resection.

PD9-06 LONG-TERM FUNCTIONAL OUTCOME AND COMPLICATIONS AFTER RADICAL CYSTECTOMY AND ORTHOTOPIC NEOBLADDER DIVERSION

You have accessJournal of UrologyUrinary Diversion: Bladder Reconstruction, Augmentation, Substitution, Diversion I1 Apr 2015PD9-06 LONG-TERM FUNCTIONAL OUTCOME AND COMPLICATIONS AFTER RADICAL CYSTECTOMY AND ORTHOTOPIC NEOBLADDER DIVERSION Michael Maidaa, Gus Miranda, Inderbir Gill, Siamak Daneshmand, and Hooman Djaladat Michael MaidaaMichael Maidaa More articles by this author , Gus MirandaGus Miranda More articles by this author , Inderbir GillInderbir Gill More articles by this author , Siamak DaneshmandSiamak Daneshmand More articles by this author , and Hooman DjaladatHooman Djaladat More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.933AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To evaluate long-term clinical outcome and complications of patients with Urothelial Bladder Cancer (UBC) who underwent radical cystectomy (RC) and orthotopic neobladder (ONB) diversion with minimum of 15 years follow-up. METHODS Using our IRB approved institutional bladder cancer database, we identified 1,964 patients who underwent RC for UBC at our institution between 1971 and 2008. 121 patients who underwent RC and ONB (Kock pouch to the urethra) with more than 15 years follow-up were subjects of this study. We reviewed the clinicopathological variables, long-term complications and outcome of this cohort. Detailed follow-up were found in 96/121 patients (79.3%). eGFR analysis was done on 32 patients with information available on BMI, pre-op Cr, and at least 2 Cr reading of 3,6,10, 15 years with 1 of the readings being at least 10 years. RESULTS Of the 121 patients, 118 were male (97.5%). Mean age at cystectomy was 59.3 years with a median follow-up of 18.3 years (range 15.1 - 23). Pathologic stage at cystectomy was <=pT1 (70, 57.9%), pT2 (32, 26.4%), pT3 (14, 11.6%) and pT4 (5, 4.1%) and pN+ (11, 9.1%) with N1 (4, 3.3%) and N2 (7, 5.8%). Neoadjuvant chemo, radiation and adjuvant chemo were used in 9 (7.4%), 2 (1.7%) and 33 (27%) cases, respectively. There were 6 patients with recurrences (3 urethral, 1 pelvis, 1 distant, and 1 upper tract) at median of 9.23 years (range 1.2 – 17.2) after cystectomy. Only 1 of the patients died of the disease (at 16.3 years); 27 died of non-cancer cause (mean 18.2; 15.2-23.0), 5 died of secondary cancer (17.1; 15.4-20.0), 3 died of unknown cause (15.3; 15.1-15.4), and 85 are alive without evidence of disease (18.5; 15.1-23.0). CONCLUSIONS The most common complications in ONB patients with more than 15 yrs follow-up were pouch-related, with afferent limb stenosis and pouch stones contributing the most. A gradual decrease in GFR over time was seen throughout the patient population, thus making renal insufficiency a prevalent complication in long-term survivors with ONB. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e197 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Michael Maidaa More articles by this author Gus Miranda More articles by this author Inderbir Gill More articles by this author Siamak Daneshmand More articles by this author Hooman Djaladat More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

PD9-07 EARLY AND LATE COMPLICATIONS OF ROBOTIC RADICAL CYSTECTOMY AND INTRA-CORPOREAL URINARY DIVERSION

INTRODUCTION AND OBJECTIVES: To evaluate long-term clinical outcome and complications of patients with Urothelial Bladder Cancer (UBC) who underwent radical cystectomy (RC) and orthotopic neobladder (ONB) diversion with minimum of 15 years follow-up. METHODS: Using our IRB approved institutional bladder cancer database, we identified 1,964 patients who underwent RC for UBC at our institution between 1971 and 2008. 121 patients who underwent RC and ONB (Kock pouch to the urethra) with more than 15 years follow-up were subjects of this study. We reviewed the clinicopathological variables, long-term complications and outcome of this cohort. Detailed follow-up were found in 96/121 patients (79.3%). eGFR analysis was done on 32 patients with information available on BMI, pre-op Cr, and at least 2 Cr reading of 3,6,10, 15 years with 1 of the readings being at least 10 years. RESULTS: Of the 121 patients, 118 were male (97.5%). Mean age at cystectomy was 59.3 years with a median follow-up of 18.3 years (range 15.1 23). Pathologic stage at cystectomy was <1⁄4pT1 (70, 57.9%), pT2 (32, 26.4%), pT3 (14, 11.6%) and pT4 (5, 4.1%) and pNþ (11, 9.1%) with N1 (4, 3.3%) and N2 (7, 5.8%). Neoadjuvant chemo, radiation and adjuvant chemo were used in 9 (7.4%), 2 (1.7%) and 33 (27%) cases, respectively. There were 6 patients with recurrences (3 urethral, 1 pelvis, 1 distant, and 1 upper tract) at median of 9.23 years (range 1.2 e 17.2) after cystectomy. Only 1 of the patients died of the disease (at 16.3 years); 27 died of non-cancer cause (mean 18.2; 15.223.0), 5 died of secondary cancer (17.1; 15.4-20.0), 3 died of unknown cause (15.3; 15.1-15.4), and 85 are alive without evidence of disease (18.5; 15.1-23.0). CONCLUSIONS: The most common complications in ONB patients with more than 15 yrs follow-up were pouch-related, with afferent limb stenosis and pouch stones contributing the most. A gradual decrease in GFR over time was seen throughout the patient population, thus making renal insufficiency a prevalent complication in long-term survivors with ONB.

Tinned fruit consumption and mortality in three prospective cohorts.

Dietary recommendations to promote health include fresh, frozen and tinned fruit, but few studies have examined the health benefits of tinned fruit. We therefore studied the association between tinned fruit consumption and mortality. We followed up participants from three prospective cohorts in the United Kingdom: 22,421 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort (1993–2012), 52,625 participants from the EPIC-Oxford cohort (1993–2012), and 7440 participants from the Whitehall II cohort (1991–2012), all reporting no history of heart attack, stroke, or cancer when entering these studies. We estimated the association between frequency of tinned fruit consumption and all cause mortality (primary outcome measure) using Cox regression models within each cohort, and pooled hazard ratios across cohorts using random-effects meta-analysis. Tinned fruit consumption was assessed with validated food frequency questionnaires including specific questions about tinned fruit. During 1,305,330 person years of follow-up, 8857 deaths occurred. After adjustment for lifestyle factors and risk markers the pooled hazard ratios (95% confidence interval) of all cause mortality compared with the reference group of tinned fruit consumption less often than one serving per month were: 1.05 (0.99, 1.12) for one to three servings per month, 1.10 (1.03, 1.18) for one serving per week, and 1.13 (1.04, 1.23) for two or more servings per week. Analysis of cause-specific mortality showed that tinned fruit consumption was associated with mortality from cardiovascular causes and from non-cardiovascular, non-cancer causes. In a pooled analysis of three prospective cohorts from the United Kingdom self-reported tinned fruit consumption in the 1990s was weakly but positively associated with mortality during long-term follow-up. These findings raise questions about the evidence underlying dietary recommendations to promote tinned fruit consumption as part of a healthy diet.

Effect of dementia diagnosis on receipt of postoperative colon cancer chemotherapy.

769 Background: Colon cancer and dementia have a high risk of co-occurrence. Prior studies found that patients with dementia have higher mortality than non-demented counterparts, mostly from non-cancer causes. We hypothesized that a dementia diagnosis using an improved algorithm would be associated with reduced use of postoperative therapy. Methods: In addition to the claims-based algorithm for dementia published by Centers for Medicare and Medicaid Services that uses SEER-Medicare Medicare Provider Analysis and Review, Carrier Claims, Home Health Agencies, and Outpatient files, we developed a medication-based algorithm using the part D file based on prescription for any of the five FDA-approved dementia drugs (donepezil, galantamine, memantine, rivastigmine, tacrine). We measured agreement between the two diagnostic algorithms with k-statistics. Using each algorithm and a final combined algorithm, we used multivariable logistic regression adjusting for demographics and disease characteristics to examine the effect of dementia on the use of post-operative colon cancer chemotherapy. Parallel analyses restricted the population to later-stage cancer patients (stage III/IV). Results: 46,126 patients diagnosed between 2007 and 2009 were identified. 20% had dementia by either of the algorithms. 9% of the dementia cases were identified through Part D data. The two algorithms showed moderate agreement (k&gt;0.49, p=0.007). After surgery, those patients with dementia by the combined algorithm were less likely to receive chemotherapy (OR = 0.641, 95% CI: 0.597-0.688). Those with dementia identified by part D data were even less likely to receive chemotherapy than those identified by the claims algorithm (OR=0.617, 95% CI: 0.466-0.816 for medication; OR=0.767, 95% CI: 0.684-0.860 for claims). A similar pattern was detected when restricting to stage III/IV patients (OR=0.667, 95% CI: 0.457-0.973). Conclusions: Part D data increases the sensitivity for identifying dementia cases in SEER-Medicare. Patients with dementia are significantly less likely to receive post-operative chemotherapy. Thus, reduced postoperative colon cancer therapy among patients with dementia may contribute to higher cancer-related mortality.

P76 When Is It Safe To Discharge Resected Stage 1a/1b Nsclc From The Clinic?

Introduction We have previously shown that the majority of recurrent disease occurs within the 2 years of lung cancer resection.1 Follow-up protocols vary between centres but often involve serial CXR examinations. At Salford we also perform a CT scan at one year after surgery. Given that the prognosis for early stage lung cancer is good, the question arises as to when it’s safe to discharge such patients from follow-up? Traditionally this has been set at 5 years. The Salford Lung Cancer d-base provides comprehensive data on all patients in Salford undergoing surgical resection including outcomes during follow-up. To date, 255 patients have undergone resection of non-small cell lung cancer and the rate of resection is increasing year on year.2 This audit sets out to review the data following introduction of routine PET scans to our service in 2005 with a view to providing guidance as to when it might be safe to discontinue regular follow-up of early stage disease. Methods All patients undergoing surgical resection were first identified from March 2006 to July 2010. Those with a post-operative stage 1A or 1B disease were then extracted; allowing a 4 year follow up for each patient. Those patients dying within 4 years of surgery from non-cancer and non-lung cancer causes were excluded to produce a selected cohort of patients. 1, 2, 3 and 4 years survival figures were then produced for each category of disease (1A, 1B and 1A+1B) to observe for any serial changes. Results A total of 89 patients underwent surgical resection during the study period of which 55 (62%) were 1A or 1B disease. After exclusions, 43 patients (23 × 1A and 20 × 1B) were available for analysis. As expected, relapse rates were low and occurred in the first 2 years. Survival rates were high but remained stable after 2 years of follow up (see [Table][1]). The use of 1 year CT scans detected just 2 relapses. Conclusions Allowing for the small numbers, the above audit supports a move away from traditional follow-up protocols to discharge alive and well patients with resected early stage disease from the clinic at 2 years. The role of imaging surveillance during the first 2 years requires further exploration.

Is thermochemotherapy with the Synergo system a viable treatment option in patients with recurrent non-muscle-invasive bladder cancer?

To prospectively evaluate the outcome of combined microwave-induced bladder wall hyperthermia and intravesical mitomycin C instillation (thermochemotherapy) in patients with recurrent non-muscle-invasive bladder cancer. Between 2003 and 2009, 21 patients (median age 70 years, range 35-95 years) with recurrent non-muscle-invasive bladder cancer (pTaG1-2 n = 9; pTaG3 n = 3; pT1 n = 9; concurrent pTis n = 8) were prospectively enrolled. Of 21 patients, 15 (71%) had received previous intravesical instillations with bacillus Calmette-Guérin, mitomycin C and/or farmorubicin. Thermochemotherapy using the Synergo system was carried out in 11 of 21 patients (52%) with curative intent, and in 10 of 21 patients (48%) as prophylaxis against recurrence. The median number of thermochemotherapy cycles per patient was six (range 1-12). Adverse effects were frequent and severe: urinary urgency/frequency in 11 of 21 patients (52%), pain in eight of 21 patients (38%) and gross hematuria in five of 21 patients (24%). In eight of 21 patients (38%), thermochemotherapy had to be abandoned because of the severity of the adverse effects (pain in 3/8, severe bladder spasms in 2/8, allergic reaction in 2/8, urethral perforation in 1/8). Overall, six of 21 patients (29%) remained free of tumor after a median follow up of 50 months (range 1-120), six of 21 patients (29%) had to undergo cystectomy because of multifocal recurrences or cancer progression and seven of 21 patients (33%) died (2/7 of metastatic disease, 5/7 of non-cancer related causes). Given the high rate of severe side-effects leading to treatment discontinuation, as well as the limited tumor response, thermochemotherapy should be offered only in highly selected cases of recurrent non-muscle-invasive bladder cancer.

Life-space mobility and mortality in older men: a prospective cohort study.

To evaluate the relationship between life-space (the extent, frequency, and independence of an individual's movement) and mortality in older men. Prospective cohort study. Six U.S. clinical sites. Men aged 71 to 98 followed from 2007 to 2011 (N = 3,892). Life-space during the past month was assessed as 0 (daily restriction to one's bedroom) to 120 (daily trips outside one's town without assistance) and categorized into 20-point intervals. The primary outcome was noncancer mortality, and secondary outcomes were all-cause, cardiovascular, cancer, and noncardiovascular noncancer mortality. Over 2.7 years (2007-2011), 373 (9.6%) men died, 230 from noncancer causes. Unadjusted risk of noncancer mortality was 41.2% in men with the lowest level of life-space (0-20 points, n = 34) and 2.4% in men with the highest level of life-space (101-120 points, n = 868), a 17 times difference. In multivariable-adjusted models, there was a strong linear trend between decreasing life-space and increasing risk of noncancer mortality (P = .005). Risk of noncancer mortality was 3.8 times higher (95% confidence interval (CI)=1.3,11.5) in men with the lowest life-space than in those with the highest life-space. Risk of noncancer mortality was 1.3 times higher (95% CI=1.1-1.5) for each standard-deviation (24 point) decrease in life-space. Risk of noncancer mortality was 1.5 times higher (95% CI=1.0-2.3) in men who did not travel beyond their neighborhood without assistance (n = 471). Results were similar for all-cause mortality and did not change after control for chronic disease burden. Life-space predicted a variety of mortality endpoints in older men; scores of 40 or less were associated with mortality independent of other risk factors.

The effectiveness of peer support interventions for community-dwelling adults with chronic non-cancer pain: a systematic review

Review question/objective The objective is to identify the effectiveness of peer support interventions in community-dwelling adults with chronic non-cancer pain. More specifically, the objectives are to identify: The effectiveness of peer support interventions in function, pain, quality of life, self-efficacy and health service utilization for adults with chronic non-cancer pain dwelling in the community, compared to those receiving usual care or other self-management interventions. The specific review question is therefore: Is peer support more effective than usual care or other self-management interventions in reducing pain and health service utilization, and enhancing function, self-efficacy and quality of life in community-dwelling older adults with chronic non-cancer pain? Inclusion criteria Types of participants Since chronic pain affects adults of all ages there will be no upper limit set; we will include participants aged 18 or over. Chronic pain in children is often managed differently than in adults, with specific guidelines, 11 therefore participants under 18 are outwith the scope of this review. Cancer pain is also considered outwith the scope of this review due to its specific nature and management 14 which often differs from non-cancer related causes of chronic pain. Adults who are hospitalized or living in residential care will also be excluded from this review. Peer support interventions in these settings are likely to differ greatly from those designed for community dwelling adults; the focus of this review is on interventions designed for community-dwelling adults. Types of intervention(s)/phenomena of interest The review will consider studies that evaluate any peer support intervention or any intervention that includes a defined element of peer support. Peer support interventions can be aimed at individuals or groups, therefore both will be included in this review. Interventions will include support groups or clubs, email discussion groups, telephone calls, home visits, and any other intervention that can be considered to be peer support. Peers will have knowledge of chronic pain. They may be self-selected or selected by health professionals, and will have received a moderate amount of training to deliver an intervention, in keeping with the definition presented above. 2 People with no training are considered natural lay helpers and are excluded from this review. People who have undergone extensive training are considered paraprofessionals and are likewise excluded from this review. In cases where it is not possible to determine whether the support was provided by a natural lay helper, peer or paraprofessional, studies will be included in order to minimize the risk of omitting relevant data. Types of comparator This review will consider studies that have compared peer support interventions to other self-management interventions that are not delivered by peers. These will include one-on-one or group interventions delivered by paraprofessionals or by health professionals. This review will also consider studies that have compared peer support to usual care. Since there is no one agreed definition of usual care for long term management of adults with chronic pain, any study that provides a description of usual care as their comparator will be included. There may also be studies in which the self-management intervention is the same in the experimental and comparison group, the only difference being the addition of a peer support element to the experimental group; these studies will also be considered. Types of outcomes This review will consider studies that include the following quantitative measures: function, pain, quality of life, self-efficacy and health service utilization. This is in keeping with recommendations for outcome measurement in chronic pain and self-management research, 13,16-17 therefore these measures should be available for consideration. Measures of function may be specific to the region of chronic pain, eg Roland Morris Low Back Pain Disability Questionnaire and Oswestry Low Back Pain Disability Questionnaire, or more general measures, eg Pain Disability Index. In addition to these measures of physical function, measures of emotional function will also be considered, eg scales that measure depression, anxiety and loneliness. Any measure of pain will be included, eg Visual Analogue Scale and Multidimensional Pain Inventory. Any quality of life measure will be included eg SF-36, Euroqol. Any measure of self-efficacy will be included, eg self-care of chronic pain and self-efficacy questionnaires. In addition, where self-management knowledge and skills have been measured these will likewise be considered (eg Health Education Impact Questionnaire) Any measure of health service utilization will be considered, such as emergency room and physician visits. Economic evaluation is however outwith the scope of this review. Where possible, outcomes measured with similar scales will be pooled together.

Long-term cause-specific mortality in survivors of adolescent and young adult bone and soft tissue sarcoma: a population-based study of 28,844 patients.

Despite improved cure rates for bone and soft tissue sarcomas, to the authors' knowledge, no large population-based study to date has evaluated long-term cause-specific mortality in patients diagnosed in the adolescent and young adult (AYA) age range (15 years-39 years). A total of 28,844 survivors of AYA bone and soft tissue sarcoma, who accrued 113,206 person-years of follow-up, were identified in the population-based Surveillance, Epidemiology, and End Results program. Standardized mortality ratios (SMR) and absolute excess risks (AER) (per 10,000 person-years) were calculated to evaluate associations with histology (chemotherapy-sensitive subtypes: Ewing sarcoma, osteosarcoma, and rhabdomyosarcoma vs all other subtypes), age, and initial therapy. All-cause mortality in survivors of AYA sarcoma was found to be significantly increased compared with that of the general population (SMR, 1.76; 95% confidence interval [95% CI], 1.60-1.92 [AER of 19]), and persisted for > 20 years (SMR, 1.39; 95% CI, 1.04-1.82 [AER of 20]). Significant excess mortality was observed for both second malignant neoplasms (SMR, 2.05; 95% CI, 1.71-2.43 [AER of 7]) and noncancer causes (SMR, 1.66; 95% CI, 1.49-1.85 [AER of 19]). Significant excess deaths occurred among patients with chemotherapy-sensitive (SMR, 2.76; 95% CI, 2.20-3.41 [AER of 32]) and nonchemosensitive (SMR, 1.63; 95% CI, 1.47-1.80 [AER of 17]) subtypes. Significantly elevated noncancer mortality in the former group included cardiovascular disease (SMR, 2.33) and infections (SMR, 15.6), whereas significant excess deaths in the latter group included diabetes (SMR, 2.40) and infections (SMR, 2.77). Survivors of AYA bone and soft tissue sarcoma experience significant long-term mortality due to second malignant neoplasms and noncancer causes. Further research is needed to develop preventive and surveillance guidelines in this understudied population to prevent and reduce long-term excess mortality.

Lifetime Increased Cancer Risk in Mice Following Exposure to Clinical Proton Beam–Generated Neutrons

To evaluate the life span and risk of cancer following whole-body exposure of mice to neutrons generated by a passively scattered clinical spread-out Bragg peak (SOBP) proton beam. Three hundred young adult female FVB/N mice, 152 test and 148 control, were entered into the experiment. Mice were placed in an annular cassette around a cylindrical phantom, which was positioned lateral to the mid-SOBP of a 165-MeV, clinical proton beam. The average distance from the edge of the mid-SOBP to the conscious active mice was 21.5 cm. The phantom was irradiated with once-daily fractions of 25 Gy, 4 days per week, for 6 weeks. The age at death and cause of death (ie, cancer and type vs noncancer causes) were assessed over the life span of the mice. Exposure of mice to a dose of 600 Gy of proton beam-generated neutrons, reduced the median life span of the mice by 4.2% (Kaplan-Meier cumulative survival, P=.053). The relative risk of death from cancer in neutron exposed versus control mice was 1.40 for cancer of all types (P=.0006) and 1.22 for solid cancers (P=.09). For a typical 60 Gy dose of clinical protons, the observed 22% increased risk of solid cancer would be expected to decrease by a factor of 10. Exposure of mice to neutrons generated by a proton dose that exceeds a typical course of radiation therapy by a factor of 10, resulted in a statistically significant increase in the background incidence of leukemia and a marginally significant increase in solid cancer. The results indicate that the risk of out-of-field second solid cancers from SOBP proton-generated neutrons and typical treatment schedules, is 6 to 10 times less than is suggested by current neutron risk estimates.

Nephron‐sparing management vs radical nephroureterectomy for low‐ or moderate‐grade, low‐stage upper tract urothelial carcinoma

To compare overall and cancer-specific outcomes between patients with upper tract urothelial carcinoma (UTUC) managed with either radical nephroureterectomy (RNU) or nephron-sparing measures (NSM) using a large population-based dataset. Using Surveillance, Epidemiology, and End Results (SEER) data, patients diagnosed with low- or moderate-grade, localised non-invasive UTUC were stratified into two groups: those treated with RNU or NSM (observation, endoscopic ablation, or segmental ureterectomy). Cancer-specific mortality (CSM) and other-cause mortality (OCM) rates were determined using cumulative incidence estimators. Adjusting for clinical and pathological characteristics, the associations between surgical type, all-cause mortality and CSM were tested using Cox regressions and Fine and Gray regressions, respectively. Of 1227 patients [mean (sd) age 70.2 (11.00) years, 63.2% male] meeting inclusion criteria, 907 (73.9%) and 320 (26.1%) patients underwent RNU and NSM for low- or moderate-grade, low-stage UTUC from 1992 to 2008. Patients undergoing NSM were older (mean age 71.6 vs 69.7 years, P < 0.01) with a greater proportion of well-differentiated tumours (26.3% vs 18.0%, P = 0.001). While there were differences in OCM between the groups (P < 0.01), CSM trends were equivalent. After adjustment, RNU treatment was associated with improved non-cancer cause survival [hazard ratio (HR) 0.78, confidence interval [CI] 0.64-0.94) while no association with CSM was demonstrable (HR 0.89, CI 0.63-1.26). Patients with low- or moderate-grade, low-stage UTUC managed through NSM are older and are more likely to die of other causes, but they have similar CSM rates to those patients managed with RNU. These data may be useful when counselling patients with UTUC with significant competing comorbidities.

Causes of death in long-term survivors of head and neck cancer.

Survivors of head and neck squamous cell carcinoma (HNSCC) face excess mortality from multiple causes. We used the population-based Surveillance, Epidemiology, and End Results (SEER) cancer registry data to evaluate the causes of death in patients with nonmetastatic HNSCC diagnosed between 1992 and 2005 who survived at least 3 years from diagnosis (long-term survivors). We used competing-risks proportional hazards regression to estimate probabilities of death from causes: HNSCC, second primary malignancy (SPM) excluding HNSCC, cardiovascular disease, and other causes. We identified 35,958 three-year survivors of HNSCC with a median age at diagnosis of 60 years (range = 18-100 years) and a median follow-up of 7.7 years (range = 3-18 years). There were 13,120 deaths during the study period. Death from any cause at 5 and 10 years was 15.4% (95% confidence interval [CI] = 15.0%-15.8%) and 41.0% (95% CI = 40.4%-41.6%), respectively. There were 3852 HNSCC deaths including both primary and subsequent head and neck tumors. The risk of death from HNSCC was greater in patients with nasopharynx or hypopharynx cancer and in patients with locally advanced disease. SPM was the leading cause of non-HNSCC death, and the most common sites of SPM death were lung (53%), esophagus (10%), and colorectal (5%) cancer. Many long-term HNSCC survivors die from cancers other than HNSCC and from noncancer causes. Routine follow-up care for HNSCC survivors should expand beyond surveillance for recurrent and new head and neck cancers.

Global dormancy of metastases due to systemic inhibition of angiogenesis.

Autopsy studies of adults dying of non-cancer causes have shown that virtually all of us possess occult, cancerous lesions. This suggests that, for most individuals, cancer will become dormant and not progress, while only in some will it become symptomatic disease. Meanwhile, it was recently shown in animal models that a tumor can produce both stimulators and inhibitors of its own blood supply. To explain the autopsy findings in light of the preclinical research data, we propose a mathematical model of cancer development at the organism scale describing a growing population of metastases, which, together with the primary tumor, can exert a progressively greater level of systemic angiogenesis-inhibitory influence that eventually overcomes local angiogenesis stimulation to suppress the growth of all lesions. As a departure from modeling efforts to date, we look not just at signaling from and effects on the primary tumor, but integrate over this increasingly negative global signaling from all sources to track the development of total tumor burden. This in silico study of the dynamics of the tumor/metastasis system identifies ranges of parameter values where mutual angio-inhibitory interactions within a population of tumor lesions could yield global dormancy, i.e., an organism-level homeostatic steady state in total tumor burden. Given that mortality arises most often from metastatic disease rather than growth of the primary per se, this finding may have important therapeutic implications.

Evaluation of traditional and novel measures of cardiac function to detect anthracycline-induced cardiotoxicity in survivors of childhood cancer

Cardiovascular disease is the leading noncancer cause of death among survivors of childhood cancer. Ejection fraction (EF) and fractional shortening (FS) are common echocardiographic measures of cardiac function, but newer imaging modalities may provide additional information about preclinical disease. This study aimed to evaluate these modalities in detection of anthracycline-induced cardiac toxicity. We compared mean radial displacement, EF, and FS among 17 adult survivors of childhood cancer exposed to ≥ 300 mg/m(2) of anthracyclines to 17 age- and sex-matched healthy controls. Survivors with a history of cardiac-directed radiation, diabetes, or heart disease were excluded. Survivors (35% male), mostly with history of treatment for a solid tumor, had a median age at diagnosis of 15 years (1-20) and 27 years (18-50) at evaluation. Median anthracycline exposure was 440 (range 300-645) mg/m(2). FS (35.5 vs. 39.6%, p < 0.01) and radial displacement (5.6 vs. 6.7 mm, p = 0.02) were significantly lower in survivors compared to controls, respectively. Although the mean EF was lower in survivors versus controls (55.4 vs. 59.7%), it was not statistically significant (p = 0.057). All echocardiographic measures were inversely associated with anthracycline dose, though radial displacement was no longer significantly correlated with anthracycline dose after controlling for survival time (p = 0.07), while EF remained correlated (p = 0.003). Radial displacement, EF, and FS are lower in childhood cancer survivors compared to controls. In this study, radial displacement added no new information beyond the traditional measures, but clinical utility remains undetermined and requires further longitudinal study.