Decade Of Diagnosis Research Articles

Relationship between Melanoma Stage at the Diagnosis and Survival During a period of 30 Years (1982-2011)

Melanoma is a malignant tumor of melanocytes, and is a potentially aggressive cancer. The incidence of melanoma is rising at a greater rate than any other cancer in the U.S. The aim of this study was to examine the association between melanoma stage at the time of diagnosis and survival among U.S. adult melanoma patients during 1982-2011. This was a secondary analysis of a non-concurrent cohort study conducted on 185219 U.S. adult patients who were diagnosed with primary cutaneous melanoma between 1982-2011. Chi-square, Kaplan-Meier, and Cox proportional hazards regression were used to analyze the data. Significance was assessed using p-value and 95% confidence interval. Men had more cutaneous melanoma. Black non-Hispanic patients were diagnosed less frequently. Patients who were married or in a domestic partnership were most likely to be diagnosed. The adjusted HR for distant melanoma was 141-fold that of in situ (95% CI 126.38-157.19). The adjusted HR was the highest in the first decade of diagnosis (1.7; 95% CI 1.6 1.75). In conclusion, survival is highly affected by melanoma stage at diagnosis. Black non-Hispanic patients had the lowest hazard ratio of all races. The sample size was large, which enhances the generalizability to the U.S. population.

Relationship between Melanoma Stage at the Diagnosis and Survival During a period of 30 Years (1982-2011)

Melanoma is a malignant tumor of melanocytes, and is a potentially aggressive cancer. The incidence of melanoma is rising at a greater rate than any other cancer in the U.S. The aim of this study was to examine the association between melanoma stage at the time of diagnosis and survival among U.S. adult melanoma patients during 1982-2011. This was a secondary analysis of a non-concurrent cohort study conducted on 185219 U.S. adult patients who were diagnosed with primary cutaneous melanoma between 1982-2011. Chi-square, Kaplan-Meier, and Cox proportional hazards regression were used to analyze the data. Significance was assessed using p-value and 95% confidence interval. Men had more cutaneous melanoma. Black non-Hispanic patients were diagnosed less frequently. Patients who were married or in a domestic partnership were most likely to be diagnosed. The adjusted HR for distant melanoma was 141-fold that of in situ (95% CI 126.38-157.19). The adjusted HR was the highest in the first decade of diagnosis (1.7; 95% CI 1.6 1.75). In conclusion, survival is highly affected by melanoma stage at diagnosis. Black non-Hispanic patients had the lowest hazard ratio of all races. The sample size was large, which enhances the generalizability to the U.S. population.

Retinoblastoma in the United States: A 40-Year Incidence and Survival Analysis.

To determine the incidence of retinoblastoma in the United States from 1973 to 2012 (40 years) and characterize the 5-year overall survival rate of the included patients. Cases of retinoblastoma were derived from the Surveillance, Epidemiology, and End Results (SEER) Program (National Cancer Institute, Rockville, MD). Incidence rates were calculated using U.S. Census Bureau data as the standard population, and trends over time were determined using the chi-square test. Hazard ratios with a 95% confidence interval (CI) were estimated for variables associated with mortality using Cox regression models. Survival rates were calculated using the Kaplan-Meier method and compared among different clinical and demographic categories. A total of 879 cases of retinoblastoma were derived from the SEER databases. The annual incidence rates of retinoblastoma for a period of 40 years were 12.14 (95% CI: 11.32 to 12.96) cases per 1 million children 4 years or younger and 0.49 (95% CI: 0.36 to 0.65) cases per 1 million children between the ages of 5 and 9 years. There was no significant trend for children 4 years or younger (P = .6324) or between the ages of 5 and 9 years (P = .7695). The 5-year overall survival rates were 97.6%, 92.7%, 91.1%, and 96.4% for children diagnosed at the first, second, third, and after the third year of life, respectively (P = .0136). The 5-year overall survival rates were 92.5% for bilateral and 96.3% for unilateral cases (P = .0116). The 5-year overall survival rates were 90.8%, 92.5%, 97.6%, 97.3% for increasing time intervals (1973 to 1979, 1980 to 1989, 1990 to 1999, and 2000 to 2012, respectively; P = .0017). The incidence rate of retinoblastoma in the United States has remained stable for the past 40 years. Survival rate analysis indicates a significant effect of laterality of tumor, age at diagnosis, and decade of diagnosis. [J Pediatr Ophthalmol Strabismus. 2018;55(3):182-188.].

Racial disparities in cancer-related survival in patients with squamous cell carcinoma of the esophagus in the US between 1973 and 2013.

BackgroundEsophageal cancer makes up approximately 1% of all diagnosed cancers in the US. There is a persistent disparity in incidence and cancer-related mortality rates among different races for esophageal squamous cell carcinoma (SCC). Most previous studies investigated racial disparities between black and white patients, occasionally examining disparities for Hispanic patients. Studies including Asians/Pacific Islanders (API) as a subgroup are rare. Our objective was to determine whether there is an association between race and cancer-related survival in patients with esophageal SCC.Methods and findingsThis was a retrospective cohort study using the National Cancer Institute’s Surveillance, Epidemiology, and End Result (SEER) database. The SEER registry is a national database that collects information on all incident cancer cases in 13 states of the United States and covers nearly 26% of the US population Patients aged 18 and over of White, Black, or Asian/Pacific Islander (API) race with diagnosed esophageal SCC from 1973 to 2013 were included (n = 13,857). To examine overall survival, Kaplan-Meier curves were estimated for each race and the log-rank test was used to compare survival distributions. Cox proportional hazards models were used to estimate unadjusted and adjusted hazard ratios with 95% confidence intervals. The final adjusted model controlled for sex, marital status, age at diagnosis, decade of diagnosis, ethnicity, stage at diagnosis, and form of treatment. Additional analyses stratified by decade of diagnosis were conducted to explore possible changes in survival disparities over time. After adjustment for potential confounders, black patients had a statistically significantly higher hazard ratio compared to white patients (HR 1.08; 95% confidence interval (CI) 1.03–1.13). However, API patients did not show a statistically significant difference in survival compared with white patients (HR 1.00; 95% CI 0.93–1.07). Patients diagnosed between 1973 and 1979 had twice the hazard of death compared to those diagnosed between 2000 and 2013 (HR 2.05, 95% CI 1.93–2.19). Patients diagnosed in 1980–1989 and 1990–1999 had had HRs of 1.59 (95% CI 1.51–1.68) and 1.33 (95% CI 1.26–1.41), respectively. After stratification according to decade of diagnosis, the HR for black patients compared with white patients was 1.14 (95% CI 1.02–1.29) in 1973–1979 and 1.12 (95% CI 1.03–1.23) in 1980–1989. These disparities were not observed after 1990; the HR for black patients compared with white patients was 1.03 (95% CI 0.93–1.13) in 1990–1999 and 1.05 (95% CI 0.96–1.15) in 2000–2013.ConclusionsBlack patients with esophageal SCC were found to have a higher hazard of death compared to white and API patients. Survival disparities between races appear to have decreased over time. Future research that takes insurance status and other social determinants of health into account should be conducted to further explore possible disparities by race.

Long-term causes of relative excess mortality after diagnosis of testicular germ cell tumor.

4553 Background: Despite today’s excellent cure rates among testicular germ cell tumor (TGCT) patients, reduced long-term relative survival (RS) is an increasing concern. We recently reported a continuing decline in RS among TGCT patients diagnosed in Norway, even beyond 30 years of follow-up. Late effects of treatment is the main culprit. Although several reports describe increased mortality from second cancer (SC), cardiovascular disease (CVD), and other causes (OC) among TGCT survivors, data beyond 20 years of follow-up are scarce. The study aim was to analyze long-term relative risks (RR) and causes of death (CD) among TGCT patients diagnosed in Norway, 1953-2014. Methods: Data sources were the Cancer Registry of Norway and the Norwegian Cause of Death Registry. All men diagnosed with TGCT in Norway during 1953-2014 were included, except spermatocytic seminomas. End of follow-up was December 31st, 2014. Patients were classified by CD, histology, disease extent and age at diagnosis, as well as by decade of diagnosis and follow-up time. Standardized mortality ratios (SMR), compared with the general Norwegian male population, were computed. Results: At end of follow-up, 2359 of 9390 patients were deceased. CD was obtained for 2320 patients; 37.6 % TGCT, 24.5 % SC, 19.1 % CVD and 18.8 % OC. SMR for all SC were significant particularly after 20 years of follow-up (1.8 – 3.1), with similar findings in localized disease at diagnosis. SMR were most consistently elevated beyond 20-30 years for SC of the pancreas, large intestine and bladder. By contrast, SMR for CVD were significant among patients diagnosed 2000-14, both before and after one year of follow-up (2.6). There were no significant SMR for CVD beyond 20 years of follow-up. Several OC SMR were elevated, such as for digestive and genitourinary diseases beyond 20-30 years (2.2 – 5.1). Conclusions: TGCT patients have increased RR of SC and OC death even beyond 20-30 years of follow-up, while the increased RR of CVD death is mostly confined to the first decade. CVD deaths in patients diagnosed 2000-14 are a particular concern. Continuing optimization of TGCT treatment and follow-up schemes is required, including further research on toxicity mechanisms.

Small cell carcinoma of the head and neck: Incidence and survival trends based on the Surveillance and Epidemiologic and End Results (SEER) analysis.

e17508 Background: Small cell carcinomas of the head and neck (SmCCHN) are rare neoplasms with an unfavorable prognosis. Population based data describing survival and prognostic factors for this malignancy are limited. Methods: Data was obtained from the US National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) database for the period 1973-2013. Patient and tumor related characteristics for SmCCHN were compared with squamous cell carcinomas (SCC) of the same anatomic sites. Survival for the two groups was compared by constructing Kaplan-Meier curves and Cox proportional hazard models with and without propensity score matching. Cox models results were expressed as hazard ratios (HR) and the corresponding 95% confidence interval (CI). Results: The dataset included 609 SmCCHN and 227943 cases of SCCHN. SCCHN patients with SmCCHN included significantly greater proportions of females and whites. SmCCHN was more likely to originate in the salivary glands and present with more advanced stage and grade. The overall 5 year and 10 year survival estimates were 27% and 18%, respectively. Corresponding values for SCCHN were 46% and 31%. The multivariable analyses adjusting for age, sex, race, marital status, year of diagnosis, stage, grade and receipt of radiation, the HR comparing SmCCHN to SCCHN was 1.53 (95% CI: 1.39-1.68). Elderly, male, black and not married persons had worse prognosis compared to their respective reference groups. Other factors independently associated with lower survival included more advanced stage and tumor grade, and earlier decades of diagnosis. In the propensity score matched analyses the corresponding HR was 1.27 (95% CI: 1.15-1.40). Conclusions: Compared to SCCHN, SmCCHN in addition to carrying a worse survival, is more likely to originate in the salivary glands, present with more advanced stage, and affect females and whites.

Risk of Cerebrovascular Events in 178 962 Five-Year Survivors of Cancer Diagnosed at 15 to 39 Years of Age: The TYACSS (Teenage and Young Adult Cancer Survivor Study).

Survivors of teenage and young adult cancer are at risk of cerebrovascular events, but the magnitude of and extent to which this risk varies by cancer type, decade of diagnosis, age at diagnosis, and attained age remains uncertain. This is the largest-ever cohort study to evaluate the risks of hospitalization for a cerebrovascular event among long-term survivors of teenage and young adult cancer. The population-based TYACSS (Teenage and Young Adult Cancer Survivor Study) (N=178,962) was linked to Hospital Episode Statistics data for England to investigate the risks of hospitalization for a cerebrovascular event among 5-year survivors of cancer diagnosed when 15 to 39 years of age. Observed numbers of first hospitalizations for cerebrovascular events were compared with that expected from the general population using standardized hospitalization ratios (SHRs) and absolute excess risks per 10 000 person-years. Cumulative incidence was calculated with death considered a competing risk. Overall, 2782 cancer survivors were hospitalized for a cerebrovascular event-40% higher than expected (SHR=1.4, 95% confidence interval, 1.3-1.4). Survivors of central nervous system (CNS) tumors (SHR=4.6, 95% confidence interval, 4.3-5.0), head and neck tumors (SHR=2.6, 95% confidence interval, 2.2-3.1), and leukemia (SHR=2.5, 95% confidence interval, 1.9-3.1) were at greatest risk. Males had significantly higher absolute excess risks than females (absolute excess risks =7 versus 3), especially among head and neck tumor survivors (absolute excess risks =30 versus 11). By 60 years of age, 9%, 6%, and 5% of CNS tumor, head and neck tumor, and leukemia survivors, respectively, had been hospitalized for a cerebrovascular event. Beyond 60 years of age, every year, 0.4% of CNS tumor survivors were hospitalized for a cerebral infarction (versus 0.1% expected), whereas at any age, every year, 0.2% of head and neck tumor survivors were hospitalized for a cerebral infarction (versus 0.06% expected). Survivors of a CNS tumor, head and neck tumor, and leukemia are particularly at risk of hospitalization for a cerebrovascular event. The excess risk of cerebral infarction among CNS tumor survivors increases with attained age. For head and neck tumor survivors, this excess risk remains high across all ages. These groups of survivors, particularly males, should be considered for surveillance of cerebrovascular risk factors and potential pharmacological interventions for cerebral infarction prevention.

Determining the epidemiologic, outcome, and prognostic factors of oral malignant melanoma by using the Surveillance, Epidemiology, and End Results database

BackgroundThe authors conducted a retrospective analysis to determine the epidemiologic, outcome, and prognostic factors in patients with oral malignant melanoma (OMM). MethodsThe authors used the US National Cancer Institute’s Surveillance, Epidemiology, and End Results database to analyze patients with OMM from 1973 to 2012. Study variables included age, sex, race, decade of diagnosis, extent of disease, tumor size, treatment modality, and socioeconomic status (SES). ResultsThe search identified 232 patients with OMM. Overall survival (OS) and disease-specific survival (DSS) were 25% and 40%, respectively, at 5 years. Age (OS, P = .004; DSS, P = .294), surgical resection (OS, P = .046; DSS, P = .005), and extent of disease (OS, P < .001; DSS, P < .001) were independent survival determinants; tumor size was an independent predictor of OS (P = .085). For confined and locally invasive disease, surgery (OS, P = .001; DSS, P = .004) and size (OS, P = .154; DSS, P = .007) were independent determinants of OS and DSS. For metastatic disease, surgery (OS, P = .675; DSS, P = .518) was a survival determinant for both OS and DSS, whereas radiotherapy predicted improved OS (hazard ratio, 0.18; 95% confidence interval, 0.03 to 0.99; P = .049). ConclusionsAge at diagnosis, decade of diagnosis, extent of disease, tumor size, and SES are prognostic factors related to OMM survival. Surgical resection and radiation therapy both improve OMM survival. Practical ImplicationsEarly and detailed examinations for OMM are critical to improving the survival rate in patients with OMM, especially in older patients and patients of lower SES.

Temporal Trends in Treatment and Subsequent Neoplasm Risk Among 5-Year Survivors of Childhood Cancer, 1970-2015

Cancer treatments are associated with subsequent neoplasms in survivors of childhood cancer. It is unknown whether temporal changes in therapy are associated with changes in subsequent neoplasm risk. To quantify the association between temporal changes in treatment dosing and subsequent neoplasm risk. Retrospective, multicenter cohort study of 5-year cancer survivors diagnosed before age 21 years from pediatric tertiary hospitals in the United States and Canada between 1970-1999, with follow-up through December 2015. Radiation and chemotherapy dose changes over time. Subsequent neoplasm 15-year cumulative incidence, cumulative burden, and standardized incidence ratios for subsequent malignancies, compared by treatment decade. Multivariable models assessed relative rates (RRs) of subsequent neoplasms by 5-year increments, adjusting for demographic and clinical characteristics. Mediation analyses assessed whether changes in rates of subsequent neoplasms over time were mediated by treatment variable modifications. Among 23 603 survivors of childhood cancer (mean age at diagnosis, 7.7 years; 46% female) the most common initial diagnoses were acute lymphoblastic leukemia, Hodgkin lymphoma, and astrocytoma. During a mean follow-up of 20.5 years (374 638 person-years at risk), 1639 survivors experienced 3115 subsequent neoplasms, including 1026 malignancies, 233 benign meningiomas, and 1856 nonmelanoma skin cancers. The most common subsequent malignancies were breast and thyroid cancers. Proportions of individuals receiving radiation decreased (77% for 1970s vs 33% for 1990s), as did median dose (30 Gy [interquartile range, 24-44] for 1970s vs 26 Gy [interquartile range, 18-45] for 1990s). Fifteen-year cumulative incidence of subsequent malignancies decreased by decade of diagnosis (2.1% [95% CI, 1.7%-2.4%] for 1970s, 1.7% [95% CI, 1.5%-2.0%] for 1980s, 1.3% [95% CI, 1.1%-1.5%] for 1990s). Reference absolute rates per 1000 person-years were 1.12 (95% CI, 0.84-1.57) for subsequent malignancies, 0.16 (95% CI, 0.06-0.41) for meningiomas, and 1.71 (95% CI, 0.88-3.33) for nonmelanoma skin cancers for survivors with reference characteristics (no chemotherapy, splenectomy, or radiation therapy; male; attained age 28 years). Standardized incidence ratios declined for subsequent malignancies over treatment decades, with advancing attained age. Relative rates declined with each 5-year increment for subsequent malignancies (RR, 0.87 [95% CI, 0.82-0.93]; P < .001), meningiomas (RR, 0.85 [95% CI, 0.75-0.97]; P = .03), and nonmelanoma skin cancers (RR, 0.75 [95% CI, 0.67-0.84]; P < .001). Radiation dose changes were associated with reduced risk for subsequent malignancies, meningiomas, and nonmelanoma skin cancers. Among survivors of childhood cancer, the risk of subsequent malignancies at 15 years after initial cancer diagnosis remained increased for those diagnosed in the 1990s, although the risk was lower compared with those diagnosed in the 1970s. This lower risk was associated with reduction in therapeutic radiation dose.

Development of Capillary Loop Convective Polymerase Chain Reaction Platform with Real-Time Fluorescence Detection

Polymerase chain reaction (PCR) has been one of the principal techniques of molecular biology and diagnosis for decades. Conventional PCR platforms, which work by rapidly heating and cooling the whole vessel, need complicated hardware designs, and cause energy waste and high cost. On the other hand, partial heating on the various locations of vessels to induce convective solution flows by buoyancy have been used for DNA amplification in recent years. In this research, we develop a new convective PCR platform, capillary loop convective polymerase chain reaction (clcPCR), which can generate one direction flow and make the PCR reaction more stable. The U-shaped loop capillaries with 1.6 mm inner diameter are designed as PCR reagent containers. The clcPCR platform utilizes one isothermal heater for heating the bottom of the loop capillary and a CCD device for detecting real-time amplifying fluorescence signals. The stable flow was generated in the U-shaped container and the amplification process could be finished in 25 min. Our experiments with different initial concentrations of DNA templates demonstrate that clcPCR can be applied for precise quantification. Multiple sample testing and real-time quantification will be achieved in future studies.

B-Cell-Based and Soluble Biomarkers in Body Liquids for Predicting Acute/Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the main curative therapy for hematological malignancy such as leukemias, lymphomas, or multiple myelomas and some other hematological disorders. In this therapy, cure of hematological diseases relies on graft-versus-malignancy effects by allogenic immune cells. However, severe posttransplant treatment-associated complications such as acute graft-versus-host disease (aGvHD) and chronic graft-versus-host disease (cGvHD) limit this approach. Most research into GvHD has concentrated on the aGvHD, while the more complex and multifaceted chronic form has been largely poorly investigated. cGvHD is a multi-organ autoimmune disorder and is the major cause of non-relapse morbidity and mortality following allo-HSCT, occurring in about 50% of patients, or 13,000–15,000 patients per year worldwide. Therefore, there is a high medical need for an early prediction of these therapy-associated toxicities. Biomarkers have gained importance over the last decade in diagnosis, in prognosis, and in prediction of pending diseases or side effects. Biomarkers can be cells, factors isolated from target tissues, or soluble factors that can be detected in body fluids. In this review, we aim to summarize some of the recent developments of biomarkers in the field of allo-HSCT. We will focus on cell-based biomarkers (B-cell subsets) for cGvHD and soluble factors including microRNA (miRNA), which are excreted into serum/plasma and urine. We also discuss the potential role of cytosolic and extracellular 70 kDa heat shock proteins (HSP70) as potential biomarkers for aGvHD and their role in preclinical models. Proteomic biomarkers in the blood have been used as predictors of treatment responses in patients with aGvHD for many years. More recently, miRNAs have been found to serve as a biomarker to diagnose aGvHD in the plasma. Another development relates to urine-based biomarkers that are usually detected by capillary electrophoresis and mass spectrometry. These biomarkers have the potential to predict the development of severe aGvHD (grades III–IV), overall mortality, and the pending development of cGvHD in patients posttransplant.

Seasonal Differences in Incidence and Survival of Hodgkin Lymphoma Depend on Geographic Location of Diagnosis

It has been previously described that Hodgkin lymphoma (HL) exhibits a seasonal incidence and mortality pattern. However, these findings arise from small datasets and are partially conflicting. The aim of the present study is to provide the most comprehensive analysis of seasonal variation in incidence and mortality risk of HL with a focus on geographic differences in a very large, high-quality dataset.All HL cases diagnosed between 1973 and 2012 in the 18 Surveillance, Epidemiology and End Results (SEER) registries were eligible (n=50,179). We excluded all death certificate and autopsy only cases (n=281), cases with unknown month of diagnosis (n=257), the "Alaska natives" (n=17) and "Rural Georgia" (n=57) registries due to low case numbers and cases with missing information on age at diagnosis (n=5) and Ann-arbor stage (n=8157), resulting in 41,405 cases being included in the study. All cases were grouped into quartiles according to the latitude of the case’s county (Quartile 1: <34.19°N; Quartile 2: 34.19°N to 38.05°N; Quartile 3: 38.05°N to 41.68°N; Quartile 4: ≥41.68°N). The monthly incidence was adjusted for length of month. Cosinor analysis was employed to examine seasonality of incidence in all cases, latitude quartiles and other preplanned subgroups, such as gender, histological subtype, Ann-arbor stage and decade of diagnosis. The overall mortality risk within 3 years following HL diagnosis was analyzed using a Cox proportional-hazards model with a dichotomized variable representing season of diagnosis (Winter: Sept.-Feb., Summer: Mar.-Aug.). Known risk factors were corrected for.HL exhibits a highly significant (p<0.001) seasonal incidence pattern with a peak in March and a trough in September. The adjusted incidence in September is approximately 15% higher than in March. This pattern was equally present in males (p<0.001) and females (p<0.001), but only present in the mixed cellularity (p<0.001), nodular sclerosis (p<0.001) and lymphocyte depleted subtypes (p=0.002). Seasonality was particularly pronounced in the age groups 20-29, 30-39 and 60-69, coinciding with age groups of increased HL incidence. All latitude quartiles showed significant seasonality patterns when analyzed separately, but the pattern was more pronounced in the two northern (≥38.05°N) quartiles with an amplitude of 0.102 ([0.073; 0.131], p<0.001) compared to the two southern (<38.05°N) quartiles with an amplitude of 0.055 ([0.026; 0.084], p<0.001). The difference was statistically significant (p=0.023).Considering all cases, a diagnosis in winter does not significantly increase the risk of dying compared to being diagnosed in summer (HR=1.030 [0.981; 1.081], p=0.234). However, looking at cases diagnosed in the two northern (≥38.05°N) quartiles showed an increased risk of death within 3 years after HL diagnosis (HR=1.082 [1.009; 1.161], p=0.027), whereas no such relationship was evident for cases diagnosed in the two southern (<38.05°N) latitude quartiles (HR=0.990 [0.926; 1.059], p=0.772). To further examine the relationship between latitude and excessive mortality risk after a diagnosis made in winter, we included a multiplicative interaction term between the dichotomous season of diagnosis variable and latitude. The hazard ratio for the interaction term was 1.119 ([1.009; 1.241], p=0.033) indicating a significant interaction in the way that mortality risk after a HL diagnosis in winter compared to summer is only increased at higher latitudes. All results were confirmed using 5 years of follow-up data.To conclude, HL exhibits a seasonal incidence and mortality pattern in this study, the most comprehensive analysis on this topic performed to date. The seasonal effect on the incidence of HL is exacerbated and the seasonal effect on mortality risk is only present at higher latitudes. Increased seasonal variations in Vitamin D levels at higher latitudes have been previously described. Therefore, a twofold protective effect of Vitamin D, where it both prevents HL development and increases the chance of survival after a diagnosis of HL is a possible explanation. Further studies, particularly those directly measuring Vitamin D levels in HL patients, are needed to improve the understanding of the role of Vitamin D in HL. DisclosuresEngert:Takeda, BMS: Consultancy, Honoraria, Research Funding.

Prognostic determinants and treatment outcomes analysis of osteosarcoma and Ewing sarcoma of the spine

Background ContextOsteosarcoma (OGS) and Ewing sarcoma (EWS) are the two classic primary malignant bone tumors. Due to the rarity of these tumors, evidence on demographics, survival determinants, and treatment outcomes for primary disease of the spine are limited and derived from small case series. PurposeTo use population-level data to determine the epidemiology and prognostic indicators in patients with OGS and EWS of the osseous spine. Study Design/SettingLarge-scale retrospective study. Patient SamplePatients diagnosed with OGS and EWS of the spine in the Surveillance, Epidemiology, and End Results (SEER) registry from 1973 to 2012. Outcome MeasuresOverall survival (OS) and disease-specific survival (DSS). MethodsTwo separate queries of the SEER registry were performed to identify patients with OGS and EWS of the osseous spine from 1973–2012. Study variables included age, sex, race, year of diagnosis, tumor size, extent of disease (EOD), and treatment with surgery and/or radiation therapy. Primary outcome was defined as OS and DSS in months. Univariate survival analysis was performed using the Kaplan-Meier method and the log-rank test. Multivariate analysis was performed using Cox proportional hazards regression models. ResultsThe search identified 648 patients with primary OGS and 736 patients with primary EWS of the spine from 1973 to 2012. Mean age at diagnosis was 48.1 and 19.9 years for OGS and EWS, respectively, with OGS showing a bimodal distribution. The median OS and DSS were 1.3 and 1.7 years, respectively, for OGS, with OGS in Paget's disease having worse OS (0.7 years) relative to the mean (log-rank p=.006). The median OS and DSS for EWS were 3.9 and 4.3 years, respectively. Multivariate cox regression analysis showed that age (OS p<.001, DSS p<.001), decade of diagnosis (OS p=.049), surgical resection (OS p<.001, DSS p<.001), and EOD (OS p<.001, DSS p<.001) were independent positive prognostic indicators for spinal OGS; radiation therapy predicted worse OS (hazard ratio [HR] 1.48, confidence interval [CI] 1.05–2.10, p=.027) and DSS (HR 1.74, CI 1.13–2.66, p=.012) for OGS. For EWS, age (OS p<.001, DSS p<.001), surgical resection (OS p=.030, DSS p=.046), tumor size (OS p<.001, DSS p<.001), and EOD (OS p<.001, DSS p<.001) were independent determinants of improved survival; radiation therapy trended toward improved survival but did not achieve statistical significance for both OS (HR 0.76, CI 0.54–1.07, p=.113) and DSS (0.76, CI 0.54, 1.08, p=.126). ConclusionsAge, surgical resection, and EOD are key survival determinants for both OGS and EWS of the spine. Radiation therapy may be associated with worse outcomes in patients with OGS, and is of potential benefit in EWS. Overall prognosis has improved in patients with OGS of the spine over the last four decades.

5-ASA and Chemoprevention in Inflammatory Bowel Disease: A Population-Based Analysis

Introduction: Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is a chronic, relapsing and remitting inflammatory disease of the gastrointestinal tract. Colorectal cancer (CRC) is a well-documented complication of IBD and is associated with IBD severity, extent and duration. Treatment with 5-aminosalicylic acid (5-ASA) reduces the risk of CRC in IBD. Our objective was to test the association of cumulative exposure to 5-ASA on CRC risk. Methods: A retrospective cohort study was performed using a population-based IBD cohort derived from administrative health data in Saskatchewan, Canada. Data were from 1979 to 2011. Exposure to 5-ASA and CRC diagnosis during the study period were examined. CRC rates were compared between 5-ASA exposed and non-exposed groups using chi-square tests. Exposure to 5-ASA was evaluated using survival analysis. To account for differences in 5-ASA exposure, propensity scores (PS) based on IBD duration, immunomodulator (IM) and anti-TNF exposure, number of endoscopies, and decade of IBD diagnosis were used to match non-exposed to exposed patients. The Kaplan-Meier estimator was used to describe the time-to-event data and Cox proportional hazards regression models were used to test the association of exposure with CRC diagnosis. Analyses were stratified by type of IBD (UC, CD). Results: A total of 8821 IBD patients were included in the study, of which 289 (3.3%) developed CRC. In the CRC-free group, 73.9% (n = 6307) of patients had exposure to 5-ASA, whereas 61.9% (n = 179) had exposure in the CRC group. Figure 1 contains a Kaplan Meier curve for time-to-diagnosis of CRC for the exposure groups. In the PS-matched cohort, the hazard ratio (HR) was 2.56 (95% CI: [1.9, 3.5]) while controlling for gender, location (urban/sub-urban/rural), diagnosis and previous corticosteroid use. The risk of CRC diagnosis was higher in the UC sub-group (HR=3.54, 95% CI: [2.3, 5.5]) when compared to the CD sub-group (1.73, 95% CI: [1.1, 2.6]), controlling for gender, location and decade of diagnosis. A dose response survival model was developed to attempt to control for the duration of 5-ASA exposure on CRC rates, and the HRs were similar.Figure 1Conclusion: This population-based cohort study suggests a chemoprotective effect of 5-ASA exposure for CRC diagnosis amongst patients with IBD. A larger protective effect was observed amongst UC patients than CD patients.

Patterns of Loss to Follow-Up Care Among Childhood Cancer Survivors.

Surveillance for long-term complications related to previous cancer therapy can help diagnose/manage chronic health conditions in childhood cancer survivors and improve survivor quality of life. However, a challenge to delivering long-term care to childhood cancer survivors is loss to follow-up; many patients discontinue care at specialized survivor care centers. The purpose of this study was to examine patterns of loss to follow-up among a cohort of childhood cancer survivors. This retrospective study examined follow-up patterns among a nonrandom representative sample of 370 childhood cancer survivors among 1116 patients from a single institution. The median age of patients at diagnosis was 10.2 years (range <1-21). Factors potentially related to follow-up were utilized to evaluate patterns of follow-up across 5-year intervals following completion of active therapy. The association between patient characteristics and follow-up was evaluated using univariate and multivariate binomial regression models. The probability of follow-up 1-5 years post-treatment was 91.2% (89.7%-92.5%) but dropped to 68.5% (66.2%-70.8%) during years 6-10, 47.7% (45.0%-50.3%) during years 11-15, and continued to steadily decrease over time. Overall, white race, diagnoses at younger ages, patients with lymphomas/leukemias, and decade of diagnosis were each associated with somewhat better rates of follow-up. These findings highlight the lack of follow-up by adult survivors of childhood cancer with only approximately one-half of patients returning for follow-up 10 years after completion of therapy. Interventions focused on educating both patients and primary care physicians may help to increase long-term follow-up care among this at-risk population.

Association between Time since Cancer Diagnosis and Health-Related Quality of Life: A Population-Level Analysis

ObjectivesTo examine the association between time since cancer diagnosis and health-related quality of life (HRQOL) among cancer survivors in remission. MethodsAnalyzing data from 3,610 cancer survivors and 59,539 individuals without cancer in the Medical Expenditure Panel Survey, we examined the relationship between time since cancer diagnosis and HRQOL, taking remission status into account and controlling for patients’ demographic characteristics and comorbidities. HRQOL measurements included the six-dimensional health state short form (derived from 36-item short form health survey) (SF-6D) utility scores, the physical component summary score, and the mental component summary score. ResultsThe relationship between time since cancer diagnosis and HRQOL varied substantially across cancer types. Compared with individuals without cancer, survivors of breast, prostate, or poor-prognosis cancer had statistically lower SF-6D scores within 2 years of diagnosis (−0.044, −0.062, and −0.088, respectively). Breast cancer survivors had SF-6D scores similar to those of individuals without cancer after 2 years, as did patients with poor-prognosis cancer after 5 years. Nevertheless, even after a period of 10 years, survivors of prostate or cervical cancer had a lower level of SF-6D scores (−0.027 and −0.042, respectively). The comparisons of physical health between cancer survivors and individuals without cancer were similar to those of SF-6D. In contrast, most cancer survivors did not experience poorer mental health; survivors of prostate or cervical cancer, however, had lower mental component summary scores after 10 years of diagnosis. ConclusionsThe level of HRQOL among cancer survivors depends on time since cancer diagnosis and cancer type. Some cancer survivors have lower HRQOL after a decade of diagnosis, even in remission.

Early mortality in lung cancer: French prospective multicentre observational study.

BackgroundDespite the progress seen in the last decade in diagnosis and treatment, lung cancer has still a bad prognosis and a substantial number of patients died within the weeks following diagnosis. The objective of this study was to quantify early mortality in lung cancer, to identify patients who are at high risk of early decease, and to describe their management in a real world.MethodsProspective observational study including consecutively all adult patients managed for primary lung cancer histologically or cytologically diagnosed in 2010 in the respiratory medicine department of one of the participating French general hospitals. Patients and cancer characteristics and first therapeutic strategy were collected at diagnosis. Dates of death were obtained from investigators or town council of the patient’s birth place. All fatal cases were considered regardless of the cause of the death. Multivariate logistic regression model was used to determine the factors significantly and independently associated with death at 1 and 3 months.ResultsSeven thousand fifty-one patients from 104 centres were included in the study. Vital status was obtained for 6,981 patients. Respectively, 678 (9.7 %) and 1,621 (23.2 %) of the 6,981 patients with available data died within 1 and 3 months following diagnosis. As compared with the other patients, they were significantly older and frailer (based on performance status [PS] and recent weight loss) and more frequently reported stage IV tumour. Overall, 64.5 % (1 month) and 42.8 % (3 months) of patients had no cancer therapy and less than 1 % were included in a therapeutic trial.ConclusionAbout one in four patients died within 3 months following lung cancer diagnosis. Early mortality mainly involves frail patients with advanced cancer and is associated with lack of cancer therapy. This supports the need for early diagnosis and clinical trials in this population. Reducing early mortality to give supplementary time to patients to organise the future is a major challenge for 21st century physicians.

Antitumor DNA‐Damaging C‐1748 is a New Inhibitor of Autophagy that Triggers Apoptosis in Human Pancreatic Cancer Cell Lines

Despite the enormous progress that has been made over the past decades in diagnosis, treatment and prevention of many types of tumors, survival rates in pancreatic cancer still remain poor. Pancreatic cancer is one of the most malignant and chemoresistant tumors and the profound mechanism supporting these phenomena is the constitutively activated prosurvival autophagy. The antitumor 1‐nitroacridine derivative C‐1748 (9‐(2′‐hydroxyethylamino)‐4‐methyl‐1‐nitroacridine) belongs to a new set of DNA‐damaging agents developed in our laboratory and is currently ready for phase I clinical trials. Here, we have uncovered a new role for C‐1748 as a potent inhibitor of autophagy in four tested pancreatic cancer cell lines: Panc‐1, MiaPaCa‐2, BxPC‐3 and AsPC‐1. C‐1748 treatment at 0.1 – 1 μM significantly reduced the typical hallmarks of autophagy, such as conversion of soluble LC3‐I protein to its lipid‐bound LC3‐II isoform or development of acidic vesicular organelles (AVOs), and importantly shifted pancreatic cancer cells into apoptotic cell death. Co‐treatment with C‐1748 and wortmannin, an early‐stage autophagy inhibitor, had a synergistic effect on autophagy inhibition and potentiated C‐1748‐induced apoptosis. In particular, compared with exposure to C‐1748 alone, the combination treatment increased time‐ and dose‐dependent cytotoxic activity of C‐1748 with the most profound effect observed in BxPC‐3 cells. Moreover, along with decrease in autophagy, co‐treatment with wortmannin significantly elevated dysfunction of mitochondria, as manifested by a drop in mitochondrial membrane potential (ΔΨm), increased caspase‐3 activation, PARP cleavage, DNA fragmentation into apoptotic bodies and accumulation of lipid droplets arising due to the interruption of autophagy. In all studied cell lines, the level of apoptotic cells after dual exposure with C‐1748 and wortmannin increased by about 20% as compared to C‐1748 alone. Surprisingly, simultaneous exposure of pancreatic cancer cells to C‐1748 in combination with the late‐stage autophagy inhibitor, chloroquine, neither significantly increased the cytotoxic activity of C‐1748 nor ameliorated its apoptosis‐inducing potential. The synergistic effect of C‐1748 and wortmannin on the inhibition of autophagy and lack of such effect when C‐1748 was co‐administered with chlroquine, suggests that C‐1748, in addition to its DNA‐damaging properties may also affects early stages of autophagy. Further studies are undergoing to uncover the role of C‐1748 as a new inhibitor of autophagy, which is especially effective against pancreatic cancer.Support or Funding InformationResearch Grant from the Polish Ministry of Science and Higher Education NR 13‐0133‐10/2011 to BB‐M, AS, EA, ZM; DoD‐W81XWH1110795 to AR‐P and UAMS TRI ABCRP funds to AR‐P

Pancreatic cancer--mechanisms of chemoresistance

Despite the enormous progress made over the past decades in diagnosis, treatment and prevention of many types of tumor, the survival rate for pancreatic cancer still remains poor. Pancreatic cancer is one of the most malignant and chemotherapy-resistant tumors. That is mainly due to the lack of effective diagnosis at an early stage of tumor development and ineffective therapy. In most patients the disease is diagnosed at an advanced, metastatic stage and only 15-20% of patients are eligible for surgical removal of the tumor, which still remains the only chance for radical treatment. Studies in recent years have not yielded significant progress in the treatment of disease, and gemcitabine or its combinations with other chemotherapeutics such as erlotinib or capecitabine still remains the standard therapy. Although mechanisms of cell death induced by gemcitabine and other chemotherapeutic agents are well known, their effectiveness is limited due to the acquisition of drug resistance by pancreatic cancer cells. So far, mechanisms of resistance have been tested for mutations in many genes--the key to proper functioning of signaling pathways in cancer cells. However, recent studies suggest a significant role of the tumor microenvironment in the development and maintaining resistance to conventionally used chemotherapeutic and targeted therapies. Drug resistance of pancreatic cancer results from multiple mechanisms, which may include the following: mutations in key genes, aberrant gene expression, deregulation of key signaling pathways, apoptotic pathways, the capacity for epithelial-mesenchymal transition (EMT), increased angiogenesis, the presence of cancer stem cells or the presence of a hypoxic microenvironment inside the tumor.

Evolving Therapeutic Strategies in Mucosal Melanoma Have Not Improved Survival over Five Decades

Mucosal melanoma represents a distinct minority of disease sites and portends a worse outcome. The ideal treatment and role of adjuvant therapy remains unknown at this time. We hypothesized that a combination of neoadjuvant and adjuvant therapies would improve survival in these aggressive melanomas. Our large, prospectively maintained melanoma database was queried for all patients diagnosed with mucosal melanoma. Over the past five decades, 227 patients were treated for mucosal melanoma. There were 82 patients with anorectal, 75 with sinonasal, and 70 with urogenital melanoma. Five-year overall survival and melanoma-specific survival for the entire cohort were 32.8 and 37.5 per cent, respectively, with median overall survival of 38.7 months. One hundred forty-two patients (63.8%) underwent adjuvant therapy and 15 were treated neoadjuvantly (6.6%). There was no survival difference by therapy type or timing, disease site, or decade of diagnosis. There was improved survival in patients undergoing multiple surgeries (Hazard Ratio [HR] 0.55, P = 0.0005). Patients receiving neoadjuvant therapy had significantly worse survival outcomes (HR 2.49, P = 0.013). Over the past five decades, improvements have not been seen in outcomes for mucosal melanoma. Although multiple surgical interventions portend a better outcome in patients with mucosal melanoma, adjuvant treatment decisions must be individualized.