Higher Disease-specific Mortality Research Articles

Rural-Urban Disparities in the Continuum of Thyroid Cancer Care: Analysis of 92,794 Cases.

Objective: Rurality is associated with higher incidence and higher disease-specific mortality for most cancers. Outcomes for rural and ultrarural ("frontier") patients with thyroid cancer are poorly understood. This study aimed to identify actionable deficits in thyroid cancer outcomes for rural patients. Methods: We queried linked California Cancer Registry and California Office of Statewide Health Planning and Development databases for patients diagnosed with thyroid cancer (1999-2017). We analyzed time from disease stage at diagnosis, time from diagnosis to surgery, receipt of appropriate radioactive iodine ablation, surveillance status, and overall and disease-specific mortality for urban, rural, and frontier patients. Cox and logistic regression models controlled for clinical and demographic covariates a stepwise manner. All incidence figures are expressed as a proportion of newly diagnosed cases. Results: Our cohort comprised 92,794 subjects: (65,475 women [70.6%]; mean age 50.0 years). Compared to urban patients, rural and frontier patients were more likely to be American Indian, White, uninsured, and from lower quintiles of socioeconomic status (p < 0.01). Distant disease at diagnosis was more common in rural (56.0 vs. 50.4 cases per 1000 new cases, p < 0.01) and frontier patients (80.9 vs. 50.4 per 1000, p < 0.01) compared to urban patients. The incidence of medullary thyroid cancer was greater in rural patients (17.9 vs. 13.6 cases per 1000, p < 0.01) and frontier patients (31.0 vs. 13.6 per 1000, p < 0.01) compared to urban patients. The incidence of anaplastic thyroid cancer was higher in frontier versus urban patients (15.5 vs. 7.1 per 1000, p < 0.01). When compared to urban patients, rural and frontier patients were more often lost to follow-up (odds ratio [OR] 1.69 [confidence interval, CI 1.54-1.85], and OR 3.03 [CI 1.89-5.26], respectively) and had higher disease-specific mortality (OR 1.18 [CI 1.07-1.30], and OR 1.92 [CI 1.22-2.77], respectively). Rural and frontier residence was independently associated with being lost to follow-up, suggesting that it is a key driver of disparities. Conclusion: Compared to their urban counterparts, rural and frontier patients with thyroid cancer present with later-stage disease and experience higher disease-specific mortality. They also are more often lost to follow-up, which presents an opportunity for targeted outreach to reduce the observed disparities in outcomes.

Racial and Ethnic Disparities in Synchronous and Metachronous Bilateral Breast Cancer.

Significant racial and ethnic disparities exist in breast cancer treatment and survival. However, studies characterizing these disparities among patients developing bilateral breast cancers (BBC) are lacking. The purpose of this study is to understand the association between race and ethnicity, sociodemographic factors, clinical variables, treatment, and mortality in patients with BBC--synchronous bilateral breast cancer (sBBC) or metachronous bilateral breast cancer (mBBC). Patients diagnosed with mBBC or sBBC in the Surveillance, Epidemiology, and End Results program between 2010 and 2016 were examined. sBBC was defined as contralateral breast cancer <1 year after the initial cancer diagnosis, and mBBC was contralateral cancer ≥1 year. Univariable analysis examined sociodemographic, clinical, and treatment variables. Kaplan-Meier curves and Cox regression models evaluated disease-specific mortality. Of the 11,493 patients that met inclusion criteria, 9575 (83.3%) had sBBC, and 1918 (16.7%) had mBBC. There were significant racial and ethnic differences in stage, tumor subtype, surgical management, and chemotherapy within sBBC and mBBC groups. On adjusted multivariate analysis of all BBC patients, Black race (HR 1.42; 95%CI 1.11-1.80; p<0.005; Ref White) was associated with a higher disease-specific mortality. Conversely, patients with mBBC had a 25% relative risk reduction in disease-specific mortality (HR 0.75; 95%CI 0.61-0.92; p<0.01) compared to sBBC. Subset analysis suggested Black Race modified the effect of sBBC on mortality (p<0.0001). Among patients with BBC, there are racial and ethnic disparities in clinical characteristics, treatment, and mortality. Future studies should focus on strategies to reduce these disparities.

Inflammatory breast cancer, trimodal treatment, and mortality: Does where you live matter?

BackgroundThe objective of this study is to examine the associations among neighborhood socioeconomic status, trimodal treatment, and disease-specific mortality among inflammatory breast cancer patients using data from the Surveillance, Epidemiology, and End Results program. MethodsPatients diagnosed with inflammatory breast cancer (T4d) from 2010 to 2016 were identified in the Surveillance, Epidemiology, and End Results program. The cohort was stratified into neighborhood socioeconomic status groups (low, middle, high) based on National Cancer Institute census tract-level index. Trimodal treatment was defined as receipt of modified radical mastectomy, chemotherapy, and radiation therapy. Bivariable analysis, log-rank test, and a Cox proportional hazards model (hazard ratio, 95% confidence interval) were conducted to evaluate the relationship between neighborhood socioeconomic status, trimodal treatment, and disease-specific mortality. ResultsIn total, 4,374 patients met study criteria. There was no difference between the neighborhood socioeconomic status groups in receipt of trimodal treatment (P = .19). On multivariable analysis, there was no association between low neighborhood socioeconomic status (hazard ratio 1.13, 0.98–1.30; ref high neighborhood socioeconomic status) or middle neighborhood socioeconomic status (hazard ratio 1.01, 0.88–1.64; ref high neighborhood socioeconomic status) and disease-specific mortality. Notably, triple negative subtype (hazard ratio 2.66, 2.21–3.20; ref luminal A) and Black race (hazard ratio 1.41, 1.16–1.72; ref White) were associated with a higher disease-specific mortality. ConclusionFor inflammatory breast cancer patients in the Surveillance, Epidemiology, and End Results program, disease-specific mortality appears to be driven by tumor biology and patient characteristics instead of treatment disparities or neighborhood socioeconomic status.

436 Identifying locations of Merkel cell carcinoma associated with higher disease-specific mortality

436 Identifying locations of Merkel cell carcinoma associated with higher disease-specific mortality

Temporal bone carcinoma: testing the prognostic value of a novel clinical and histological scoring system.

Our group recently proposed thenovel Padova prognostic scoring system for temporal bone carcinoma (TBSCC) that considers: the revised Pittsburgh staging system; radiological dura mater involvement; non-anterior spread (medial, inferior orposterior into the temporal bone and skull base) of T4 tumors; and histological grade. The aim of the present study was to validate this prognostic TBSCC scoring system in a case series selected from the literature. A search was run to identify studies on TBSCC reporting the variables included in our score for each patient. Then our system was applied to the data extracted. Only two published investigations reported all the clinical and pathological data required for our scoring system. In one series from the Gruppo Otologico in Piacenza (Italy), a significantly higher recurrence rate (p = 0.008), shorter disease-free survival (DFS) (p = 0.001), higher disease-specific mortality (DSM) (p = 0.006), and shorter disease-specific survival (DSS) (p = 0.004) were associated with scores ≥ 5. Receiver operating curve (ROC) analysis showed an AUC of 0.804 for TBSCC recurrence, and 0.832 for DSM. In a series from Kyushu University Hospital (Japan), a significantly higher DSM (p = 0.018) and shorter DSS (p = 0.021) were associated with scores ≥ 5. ROC analysis showed an AUC of 0.812 for tumor relapse and 0.790 for DSM. Our TBSCCPadova scoring system confirmed its validity when applied to the only two international TBSCC series providing the required data. These preliminary results need to be confirmed in a multi-center prospective setting.

Breast Cancer Mortality in Older and Younger Patients in California.

Breast cancer in younger patients is reported to be more aggressive and associated with lower survival; however, factors associated with age-specific mortality differences have not been adequately assessed. We used data from the population-based California Cancer Registry for 38,509 younger (18-49 years) and 121,573 older (50 years and older) women diagnosed with stage I to III breast cancer, 2005-2014. Multivariable Cox regression models were used to estimate breast cancer-specific mortality rate ratios (MRR) and 95% confidence intervals (CI), stratified by tumor subtype, guideline treatment, and care at an NCI-designated cancer center (NCICC). Older breast cancer patients at diagnosis experienced 17% higher disease-specific mortality than younger patients, after multivariable adjustment (MRR = 1.17; 95% CI, 1.11-1.23). Higher MRRs (95% CI) were observed for older versus younger patients with hormone receptor (HR)+/HER2- (1.24; 1.14-1.35) and HR+/HER2+ (1.38; 1.17-1.62), but not for HR-/HER2+ (HR = 0.94; 0.79-1.12) nor triple-negative breast cancers (1.01; 0.92-1.11). The higher mortality in older versus younger patients was diminished among patients who received guideline-concordant treatment (MRR = 1.06; 95% CI, 0.99-1.14) and reversed among those seen at an NCICC (MRR = 0.86; 95% CI, 0.73-1.01). Although younger women tend to be diagnosed with more aggressive breast cancers, adjusting for these aggressive features results in older patients having higher mortality than younger patients, with variations by age, tumor subtype, receipt of guideline treatment, and being cared for at an NCICC. Higher breast cancer mortality in older compared with younger women could partly be addressed by ensuring optimal treatment and comprehensive patient-centered care.

Malignant otitis externa in Australian Aboriginal patients: A 9-year retrospective analysis from the Northern Territory.

In the Australian Aboriginal population, type 2 diabetes occurs at a much higher prevalence, with a much younger age of onset of the disease and its complications. Despite the clear association with malignant otitis externa, no previous studies have examined malignant otitis externa in this population. This study explores the pattern of malignant otitis externa amongst Australian Aboriginal patients in the Northern Territory. Retrospective case series. Otolaryngology unit in a tertiary referral hospital in Northern Territory, Australia. Patients admitted with malignant otitis externa between January 2007 and October 2016 were identified by reviewing case notes. Patients diagnosed with malignant otitis externa based on results from clinical, microbiological and radiological criteria were included. Complications rates, duration of hospital stay and parenteral antibiotics, age of onset and causative organisms. Nine patients were included. Six were Australian Aboriginal - all from regional centres. The most common causative organism was Pseudomonas aeruginosa. There was a higher-than-expected occurrence of fungal malignant otitis externa (33% of Australian Aboriginal patients), who tended to be younger at diagnosis, had longer hospital stays and had a higher disease-specific mortality. Over half of the patients did not receive follow-up gallium bone scans to monitor disease resolution, reflecting the limitations of rural health care. Malignant otitis externa in the Australian Aboriginal population is a challenging disease with high complication and mortality rates. Their rural and remote distribution is a significant barrier to specialist investigation and care. Providing effective care for this disease requires improved access to high-quality primary health care and tertiary specialist services.

Surgically Treated Retroperitoneal Sarcoma: A Population-based Competing Risks Analysis

BackgroundData regarding the relationship between non–disease-specific (NDSM) and disease-specific mortality (DSM) in patients with surgically treated nonmetastatic retroperitoneal sarcoma (nmRPS) are lacking. ObjectiveTo examine the rates of NDSM and DSM among patients with surgically treated nmRPS. Design, setting and participantsWe used the Surveillance, Epidemiology and End Results (SEER) database (2004–2014) to obtain data for patients with surgically treated nonmetastatic RPS. Outcome measurements and statistical analysesThe 5-yr DSM and NDSM rates were generated via competing risks regression (CRR) methodologies. Multivariable CRR models were used to test the effects of age, histologic subtype, grade, size, and radiotherapy (RT) status on NDSM and DSM. Results and limitationsOverall, 231 (26.8%) and 57 patients (6.7%) died from DSM and NDSM, respectively. Following stratification according to age, histologic subtype, grade, size, and RT status, the proportion of patients who succumbed to NDSM was higher for patients with age above the median, liposarcoma histologic subtype, low grade, and tumor size ≥17cm. DSM rates were also higher among patients with age above the median, leiomyosarcoma histologic subtype, high grade, and tumor size ≥17cm. Multivariable CRR models revealed that age above the median was associated with higher NDSM (hazard ratio [HR]1.7, 95% confidence interval [CI] 1.1–2.7; p=0.019). Conversely, leiomyosarcoma (HR 1.9, 95% CI 1.4–2.6; p<0.0001), sarcoma not otherwise specified (HR 2.4, 95% CI 1.5–3.8; p<0.0001) and other RPS (HR 2, 95% CI 1.2–3.4; p=0.01) histologic subtypes, high grade (HR 3, 95% CI 2.3–4; p<0.0001), and tumor size above the median (HR 1.4, 95% CI 1.1–3.8; p=0.012) were associated with higher DSM. This is a retrospective study and misclassification bias may be present because of the reliability of the distinction between DSM and NDSM. ConclusionsThe impact of NDSM in surgically treated nmRPS is not trivial, particularly among patients with favorable characteristics such as liposarcoma histologic subtype and low-grade tumors. Patient summaryMortality from causes not related to the specific disease is important in patients with retroperitoneal sarcoma (RPS) treated surgically. In particular, patients with good tumor characteristics, namely liposarcoma histologic subtype and low grade, most often do not die from their cancer but succumb to causes other than RPS. Unfortunately, tumor characteristics and radiotherapy administration shed relatively little light on predicting mortality from causes other than cancer in patients with surgically treated RPS. Our report compares the risk of dying from RPS with that of dying from other causes according to the type of surgically treated sarcoma.

Genotypic characteristics and their association with phenotypic characteristics of hereditary medullary thyroid carcinoma in Korea

BackgroundHereditary medullary thyroid carcinoma can present as a part of multiple endocrine neoplasia syndrome by rearranged during transfection gene mutation. We evaluated the prevalence of rearranged during transfection gene mutation in patients who have medullary thyroid carcinoma and the correlations of genotype with medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism according to the revised American Thyroid Association risk level. MethodsA total of 331 patients were diagnosed with medullary thyroid carcinoma, 172 of whom were tested for the rearranged during transfection germline mutation by sequencing of exon 8, 10, 11, and 13–16. These patients were diagnosed during the years 1982–2012 at 2 Korean tertiary hospitals. Patients were analyzed according to the route of diagnosis (screened versus index cases) or the mutational site of rearranged during transfection gene (the American Thyroid Association risk group). ResultsRearranged during transfection mutation was found in 23.8% of patients tested, showing a decreasing trend with time. The most commonly mutated codon was codon 634 (37.1%), followed by codon 918 (14.3%). rearranged during transfection–positive patients were younger than rearranged during transfection–negative patients, although no other clinicopathologic characteristics differed. Screened cases were younger and had smaller tumors than index cases. Among rearranged during transfection–positive patients, pheochromocytoma manifested in 35.1% and hyperparathyroidism in 7.0%. Notably, pheochromocytoma and hyperparathyroidism emerged at any time after the diagnosis of medullary thyroid carcinoma. The American Thyroid Association risk-group analysis demonstrated that medullary thyroid carcinoma patients in the highest risk group were younger, had larger tumors, and higher disease-specific mortality. Similar results for pheochromocytoma were found, according to the American Thyroid Association risk group, although the results were not significant. ConclusionsKorean patients who have medullary thyroid carcinoma showed a similar distribution of rearranged during transfection gene mutation with those in Western countries. The American Thyroid Association risk classification was shown to be useful for pheochromocytoma, as well as for medullary thyroid carcinoma. Familial screening for rearranged during transfection mutation and lifelong monitoring for associated pheochromocytoma should be emphasized in hereditary medullary thyroid carcinoma.

Pretreatment neutrophil-to-lymphocyte ratio is correlated with response to neoadjuvant chemotherapy as an independent prognostic indicator in breast cancer patients: a retrospective study.

BackgroundA high neutrophil-to-lymphocyte ratio (NLR) may be related to increased mortality in patients with lung, colorectal, stomach, liver, and pancreatic cancer. To date, the utility of NLR to predict the response to neoadjuvant chemotherapy (NAC) has not been studied. The aim of our study was to determine whether the NLR is a predictor of response to NAC and to investigate the prognostic impact of the NLR on relapse-free survival (RFS) and breast cancer-specific survival (BCSS) in patients with breast cancer who received NAC.MethodsWe retrospectively studied patients who received NAC and subsequent surgical therapy for stage II–III invasive breast carcinoma at Sun Yat-sen Memorial Hospital between 2001 and 2010. The correlation of NLR with the pathological complete response (pCR) rate of invasive breast cancer to NAC was analyzed. Survival analysis was used to evaluate the predictive value of NLR.ResultsA total of 215 patients were eligible for analysis. The pCR rate in patients with lower pretreatment NLR (NLR < 2.06) was higher than those with higher NLR (NLR ≥ 2.06) (24.5 % vs.14.3 %, p < 0.05). Those patients with higher pretreatment NLR (NLR ≥ 2.1) had more advanced stages of cancer and higher disease-specific mortality. Through a multivariate analysis including all known predictive clinicopathologic factors, NLR ≥ 2.1 was a significant independent parameter affecting RFS (HR: 1.57, 95 % CI: 1.05-3.57, p < 0.05) and BCSS (HR: 2.21, 95 % CI: 1.01-4.39, p < 0.05). Patients with higher NLR (NLR ≥ 2.1) before treatment showed significantly lower relapse-free survival rate and breast cancer-specific survival rate than those with lower NLR (NLR <2.1) (log-rank p = 0.0242 and 0.186, respectively).ConclusionsPretreatment NLR < 2.06 is associated with pCR rate, suggesting that NLR may be an important factor predicting the response to NAC in breast cancer patients. NLR is an independent predictor of RFS and BCSS in breast cancer patients with NLR ≥ 2.1 who receive NAC. We suggest prospective studies to evaluate NLR as a simple prognostic test for breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2352-8) contains supplementary material, which is available to authorized users.

Predictors of Disease Recurrence and Survival in Esophageal Adenocarcinomas With Complete Response to Neoadjuvant Therapy.

Complete response to neoadjuvant therapy, determined by pathologic examination of the resection specimen (pCR), is associated with a favorable outcome in esophageal adenocarcinomas (EAC), but there is significant heterogeneity in survival reported within this group. Our aim was to determine predictors of disease recurrence (DR) and survival in EAC patients with pCR to neoadjuvant therapy. A total of 93 EAC patients with pCR to neoadjuvant therapy were identified, and a predetermined set of clinicopathologic variables was examined, including patient age, sex, tumor location, pretreatment tumor size, endoscopic ultrasound T and N stage, histologic tumor type, and grade in pretreatment biopsies. The esophagectomy specimens were evaluated for the extent of sampling of the tumor bed, depth of treatment-related changes, presence of treatment effect in lymph nodes, and the total number of lymph nodes examined. Complete histologic examination of the tumor bed was the most significant predictor of favorable outcome for both DR (hazard ratio [HR]=0.42; 95% confidence interval [CI]: 0.21-0.82; P=0.011) and disease-specific mortality (HR=0.40; 95% CI: 0.22-0.70; P<0.01). The presence of a high-grade adenocarcinoma component in pretreatment biopsies (HR=2.19; 95% CI: 1.22-3.94; P<0.01) was associated with a higher disease-specific mortality, and involvement of the gastroesophageal junction (HR=2.37; 95% CI: 1.11-5.06; P=0.026) was associated with a higher rate of DR. Heterogeneity in outcomes for EAC patients with pCR to therapy can be explained by adequacy of histologic examination of the tumor bed, high tumor grade, and involvement of the gastroesophageal junction.

Evidence of an Oncogenic Role for Aberrant Tox Activation in Cutaneous T Cell Lymphoma

Cutaneous T cell lymphoma (CTCL) consists of two main subtypes: mycosis fungoides (MF), which primarily affects the skin; and Sézary syndrome (SS), which is characterized by the presence of circulating malignant Sézary cells. Although defective apoptosis and cell cycle progression have been implicated in CTCL disease development, the precise molecular mechanism underlying these abnormalities is only partially understood. Recently our group showed that TOX, a transcription factor transiently expressed during thymocyte development, was ectopically expressed in the malignant CD4+ T cells in MF skin lesions. Normally in mature CD4+ T cells, TOX is expressed at very low levels. Not only is TOX highly expressed in the infiltrating CD4+ T cells in MF skin lesions, but its expression levels also inversely correlate with the clinical outcome of CTCL patients. However, its involvement in other types of CTCL remains unknown and its biological effects on CTCL pathogenesis have not been explored. In this study, we sought to examine if aberrant TOX expression occurs in SS (a leukemic variant of CTCL), and whether it contributes to CTCL pathogenesis. We found that TOX expression is also enhanced significantly in primary CD4+CD7- cells from SS patients (n=12), and its enhanced transcript levels correlate with higher disease-specific mortality (P=0.039). To investigate the role of TOX in CTCL, we corrected the ectopic TOX expression by lentiviral-shRNA-mediated TOX gene knock-down in CTCL cell lines (Hut78, HH, and SZ4). In all three cell lines, this resulted in markedly increased apoptosis (measured using Annexin V apoptosis assay, 2-3 fold, P<0.05) and reduced cellular proliferation (assessed by BrdU incorporation assay and colony formation in 3D cultures, 1.5-12 fold, P<0.05). In line with these phenotypes, TOX knock-down led to an increase in cleaved caspases (3, 9) and enhanced expression of multiple cell cycle inhibitors (CDKN1B, CDKN1C). Moreover, to test the effect of TOX suppression on the tumor-inducing ability of CTCL cells in vivo, we injected TOX-suppressed cells or control CTCL cells (1x106 per injection site) subcutaneously into NOD-SCID IL2rγ null (NSG) mice and monitored local tumor formation. Control CTCL cells (Hut78, HH) induced local tumor growth in six out of six mice within 2 weeks of injection, with enlargement progressively to 1.5cm in diameter within 4 weeks of injection. In contrast, TOX silencing effectively reduced the tumor volume induced by HH cells (n=6) and abolished the tumor-forming ability of Hut78 cells (n=6). Since TOX is a DNA-binding nuclear protein, we next sought to explore the potential downstream molecular partners of TOX by performing comparative transcriptome analysis between TOX-suppressed cells and control CTCL cells (Hut78, HH). The expression of several tumor suppressor genes, including SMAD3 and FOXO3, was increased upon TOX knock-down in both Hut78 and HH cell lines. Pathway analyses of the differentially-expressed genes uncovered activation of apoptotic pathways and cell cycle arrest processes upon TOX suppression. These findings were validated using quantitative RT-PCR. In conclusion, our results indicate that ectopic expression of TOX in CTCL cells causes the proliferation/apoptosis balance to shift toward proliferation through suppression of the transcription of multiple tumor suppressors. Therefore abolishing TOX activity may be a promising treatment strategy for CTCL. DisclosuresNo relevant conflicts of interest to declare.

Comparison of Hispanic and non-Hispanic patients with HCC.

294 Background: In the U.S., Hispanics have a higher incidence of hepatocellular cancer (HCC) and higher disease-specific mortality. The country of origin for Hispanics varies throughout the U.S. However, little is known about Hispanics with HCC in the Northeast. We compared Hispanic and non-Hispanic patients with HCC at a Boston teaching hospital. Methods: Hispanic patients with HCC seen at Beth Israel Deaconess Medical Center (BIDMC) from 1998-2012 were identified in our database. Ethnicity was determined from demographic and language preference information in electronic medical records and supplemented by comparing surnames with the 1990 Census Spanish Surname List. The comparison group was identified by randomly choosing non-Hispanic patients diagnosed the same years as Hispanic patients. We compared both groups using Chi Squared test. Results: 59 Hispanic and 89 non-Hispanic patients with HCC were included in the analysis. The majority (48%) of Hispanic HCC patients were Puerto Rican. Although the median age at diagnosis was similar (59.1 vs 60.3 years for Hispanics and non-Hispanics), there were more women in the Hispanic cohort (28.8% vs 12.4% p0.012). Hispanics had greater odds of not having private insurance (OR 4.24, 95%CI: 2.101, 8.554). Evaluation of HCC risk factors revealed Hispanics were significantly more likely to have hepatitis C (OR 3.68, 95% CI: 1.830, 7.420). In addition, the incidence of Metabolic Syndrome was significantly higher for Hispanics (44.7% vs. 21.7% p0.025). Although individual components of metabolic syndrome were higher in Hispanics, they were not statistically significant: hypertension (52.5% vs 40.4%), Diabetes Mellitus (39% vs 25%), BMI ≥ 30 (39% vs 27%), hypertrigylceridemia (57% vs 52%) and low HDL levels (50% vs 41%). Hispanics were more likely to have received Transarterial Chemoembolization (TACE) and Radiofrequency ablation (RFA) treatments (OR 2.48, 95% CI: 1.261, 4.858). Conclusions: Hispanic HCC patients at BIDMC were more likely to have hepatitis C, metabolic syndrome and to be female than their non-Hispanic counterparts. Outreach to Hispanic communities to identify patients with hepatitis C and metabolic syndrome, particularly in women, may improve HCC prevention, screening and treatment outcomes.

Association Between Molecular Subtypes of Colorectal Cancer and Patient Survival

Colorectal cancer (CRC) is a heterogeneous disease that can develop via several pathways. Different CRC subtypes, identified based on tumor markers, have been proposed to reflect these pathways. We evaluated the significance of these previously proposed classifications to survival. Participants in the population-based Seattle Colon Cancer Family Registry were diagnosed with invasive CRC from 1998 through 2007 in western Washington State (N = 2706), and followed for survival through 2012. Tumor samples were collected from 2050 participants and classified into 5 subtypes based on combinations of tumor markers: type 1 (microsatellite instability [MSI]-high, CpG island methylator phenotype [CIMP] -positive, positive for BRAF mutation, negative for KRAS mutation); type 2 (microsatellite stable [MSS] or MSI-low, CIMP-positive, positive for BRAF mutation, negative for KRAS mutation); type 3 (MSS or MSI low, non-CIMP, negative for BRAF mutation, positive for KRAS mutation); type 4 (MSS or MSI-low, non-CIMP, negative for mutations in BRAF and KRAS); and type 5 (MSI-high, non-CIMP, negative for mutations in BRAF and KRAS). Multiple imputation was used to impute tumor markers for those missing data on 1-3 markers. We used Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations of subtypes with disease-specific and overall mortality, adjusting for age, sex, body mass, diagnosis year, and smoking history. Compared with participants with type 4 tumors (the most predominant), participants with type 2 tumors had the highest disease-specific mortality (HR = 2.20, 95% CI: 1.47-3.31); subjects with type 3 tumors also had higher disease-specific mortality (HR = 1.32, 95% CI: 1.07-1.63). Subjects with type 5 tumors had the lowest disease-specific mortality (HR = 0.30, 95% CI: 0.14-0.66). Associations with overall mortality were similar to those with disease-specific mortality. Based on a large, population-based study, CRC subtypes, defined by proposed etiologic pathways, are associated with marked differences in survival. These findings indicate the clinical importance of studies into the molecular heterogeneity of CRC.

Active surveillance: a cautionary tale

Objective To determine if the practice of active surveillance for prostate cancer (PCa) at the District General Hospital (DGH) level produces outcomes in keeping with those published from clinical trials. Subjects A cohort of 47 patients started on active surveillance for prostate cancer in 2002–2003. Methods Retrospective review of case notes, electronic records and the regional cancer register. Results This cohort of patients had significantly higher disease-specific mortality and greater progression to palliative forms of management compared to previously published studies. Conclusion The implementation of AS in routine clinical practice may be inconsistent, potentially leading to compromised patient outcomes.

Impact of screening and treatment on racial and ethnic differences in health service use, cost, and mortality among advanced (T3 or greater) prostate cancer patients.

131 Background: Limited information is available regarding the association between race/ethnicity, health service use, cost, and mortality in older patients with advanced (T3 or greater) stage prostate cancer. The objective is to analyze the race/ethnic differences in mortality, cost, and assess the mediating effect of prostate cancer screening and treatment on these differences in fee-for-service Medicare patients with advanced prostate cancer Methods: Retrospective, observational, case-control study using SEER-Medicare linked data. Cohort consisted of 15,054 elderly men diagnosed with advanced stage prostate cancer between 2001and 2004 and followed retrospectively for up to 2009. Cancer-free controls from Medicare data were used to determine the incremental cost of advanced stage prostate cancer. Racial/ethnic variation in health service use, cost, and mortality were analyzed using Poisson, GLM log-link, and Cox regression models. Results: For the age 66 to 75 and 76 to 85, age groups, racial/ethnic differences in health service use, cost, and all cause mortality were observed. Blacks were less likely to have received prostate cancer screening in the year prior to diagnosis of advanced prostate cancer, less likely to have received any treatment after diagnosis and had higher disease specific mortality. After adjusting for prostate cancer screening and treatment across age groups however, odds of prostate cancer-specific mortality were comparable between racial/ethnic groups suggesting that screening may have some mitigating effect on outcomes in the AA population HR 1.23 (1.07-1.41) versus HR 1.12(0.98-1.29). Conclusions: The pattern of racial/ethnic disparity varies by age group with higher mortality among black men. This may be attributable to disparity in prostate cancer screening or treatment. This suggests that the lack of consideration for racial considerations in the U.S. Preventive Services Task Force PSA recommendations could have disparate racial impact.

Management of Recurrent Differentiated Thyroid Carcinoma

Patients with well differentiated thyroid carcinoma (WDTC) generally have good prognosis with appropriate therapy, but those with recurrences have higher disease specific mortality and poor quality of life requiring clinical attention. Recurrences occur in 5-20% as loco-regional form and as distant metastasis in 10-20% in long-term follow-up after initial therapy. Soft tissue recurrences as a form of local recurrence require aggressive therapy including wide excision and postoperative adjuvant therapy as they have dismal prognosis. There are controversies in proper management of loco-regional recurrences in neck lymph node, because improvement in clinical outcome of those patients through randomized, prospective study had never been documented and because it is not clear if lymph node recurrences could be a focus of further metastasis of cancer cells. Management includes surgery (compartment-oriented lymph node dissection), alcohol injection or radiofrequency ablation and simple observation. Adjuvant radioiodine therapy is not useful after re-operation, especially high dose radioiodine had been done as initial therapy. Recurrences as distant metastasis require thorough evaluation and proper management according to site and progression of each lesion. Palliative surgery if critical structure is endangered, radioiodine therapy in “radioactive iodine (RAI)-avid” lesions, external beam radiation therapy or IV bisphosphonate, embolization should be considered in bone metastasis according to clinical setting. RAI-avid lung metastasis can be managed with radioiodine, but there is no available therapeutic modality in ”non-RAI-avid” lung metastatic lesions. Clinical trials using new targeted agents can be considered in those patients. There had been many trials to enhance/restore iodine uptake in metastatic lesions, but there is no clinically available agent yet. Further studies are required for development of agents to restore/enhance iodine uptake to improve efficacy of RAI therapy.

Association Between Age at Diagnosis and Disease-Specific Mortality Among Postmenopausal Women With Hormone Receptor–Positive Breast Cancer

Context: In addition to classic tumor-related prognostic factors, patient characteristics may be associated with breast cancer outcome. Objective: To assess the association between age at diagnosis and breast cancer outcome in postmenopausal women with hormone receptor-positive breast cancer. Design, Setting, and Patients: Study analysis of 9766 patients enrolled in the TEAM (Tamoxifen Exemestane Adjuvant Multinational) randomized clinical trial between January 2001 and January 2006. Age at diagnosis was categorized as younger than 65 years (n=5349), 65 to 74 years (n=3060), and 75 years or older (n=1357). Main Outcome Measures: Primary end point was disease-specific mortality; secondary end points were other-cause mortality and breast cancer relapse. Results: During median follow-up of approximately 5.1 years, there were a total of 1043 deaths. Disease-specific mortality, as a proportion of all-cause mortality, decreased with categorical age group (78% [<65 years], 56% [65-74 years], and 36% [≥75 years]; P < .001). In multivariable analyses, compared with patients younger than 65 years, disease-specific mortality increased with age for patients aged 65 to 74 years (hazard ratio [HR], 1.25; 95% CI, 1.01-1.54); and patients aged 75 years or older (HR, 1.63; 95% CI, 1.23-2.16) (P < .001). Similarly, breast cancer relapse increased with age for patients aged 65-74 years (HR, 1.07; 95% CI, 0.91-1.25 and patients aged 75 years or older (HR, 1.29; 95% CI, 1.05-1.60) (P=.06). Other-cause mortality increased with age in patients aged 65 to 74 years (HR, 2.66; 95% CI, 1.96-3.63) and patients aged 75 years or older (HR, 7.30; 95% CI, 5.29-10.07) (P < .001). Conclusion: Among postmenopausal women with hormone receptor-positive breast cancer, increasing age was associated with a higher disease-specific mortality.

Association Between Age at Diagnosis and Disease-Specific Mortality Among Postmenopausal Women With Hormone Receptor–Positive Breast Cancer

In addition to classic tumor-related prognostic factors, patient characteristics may be associated with breast cancer outcome. To assess the association between age at diagnosis and breast cancer outcome in postmenopausal women with hormone receptor-positive breast cancer. Study analysis of 9766 patients enrolled in the TEAM (Tamoxifen Exemestane Adjuvant Multinational) randomized clinical trial between January 2001 and January 2006. Age at diagnosis was categorized as younger than 65 years (n=5349), 65 to 74 years (n=3060), and 75 years or older (n=1357). Primary end point was disease-specific mortality; secondary end points were other-cause mortality and breast cancer relapse. During median follow-up of approximately 5.1 years, there were a total of 1043 deaths. Disease-specific mortality, as a proportion of all-cause mortality, decreased with categorical age group (78% [<65 years], 56% [65-74 years], and 36% [≥75 years]; P < .001). In multivariable analyses, compared with patients younger than 65 years, disease-specific mortality increased with age for patients aged 65 to 74 years (hazard ratio [HR], 1.25; 95% CI, 1.01-1.54); and patients aged 75 years or older (HR, 1.63; 95% CI, 1.23-2.16) (P < .001). Similarly, breast cancer relapse increased with age for patients aged 65-74 years (HR, 1.07; 95% CI, 0.91-1.25 and patients aged 75 years or older (HR, 1.29; 95% CI, 1.05-1.60) (P = .06). Other-cause mortality increased with age in patients aged 65 to 74 years (HR, 2.66; 95% CI, 1.96-3.63) and patients aged 75 years or older (HR, 7.30; 95% CI, 5.29-10.07) (P < .001). Among postmenopausal women with hormone receptor-positive breast cancer, increasing age was associated with a higher disease-specific mortality.

Smoking and prostate cancer survival and recurrence

Smoking and prostate cancer survival and recurrence