Use of Antihypertensive Medications and Risk of Adverse Breast Cancer Outcomes in a SEER-Medicare Population.

Background: It is unclear if use of common antihypertensive medications influences the risk of adverse breast cancer outcomes.Methods: Using the linked Surveillance, Epidemiology and End-Results (SEER)-Medicare database, we identified 14,766 women between ages 66 and 80 years diagnosed with incident stage I/II breast cancer between 2007 and 2011. Medicare Part D data were obtained to characterize women's post-cancer use of various antihypertensive medications. Outcomes included a second breast cancer event (SBCE; a composite outcome defined as the first of a recurrence or a second contralateral primary breast cancer), breast cancer recurrence, and breast cancer-specific mortality. Time-varying Cox proportional hazard models were used to estimate hazard ratios (HR) and their associated 95% confidence intervals (CI).Results: There were 791 SBCEs, 627 breast cancer recurrences, and 237 breast cancer deaths identified over a median follow-up of 3 years. Use of diuretics (n = 8,517) after breast cancer diagnosis was associated with 29% (95% CI, 1.10-1.51), 36% (95% CI, 1.14-1.63) and 51% (95% CI, 1.11-2.04) higher risks of a SBCE, recurrence, and breast cancer death, respectively. Compared with nonusers, ß-blockers users (n = 7,145) had a 41% (95% CI, 1.07-1.84) higher risk of breast cancer death. Use of angiotensin II receptor blockers, calcium channel blockers and angiotensin-converting enzyme inhibitors were not associated with risks of breast cancer outcomes.Conclusions: Use of diuretics and ß-blockers may be associated with increased risk of breast cancer outcomes among older women.Impact: Most antihypertensive medications are safe with respect to breast cancer outcomes, but more research is needed for diuretics and ß-blockers. Cancer Epidemiol Biomarkers Prev; 26(11); 1603-10. ©2017 AACR.

Prior cancer does not adversely affect survival in locally advanced lung cancer: A national SEER-medicare analysis.

INTRODUCTION: Management of locally advanced non-small cell lung cancer is among the most highly contested areas in thoracic oncology. In this population, a history of prior cancer frequently results in exclusion from clinical trials and may influence therapeutic decisions. We therefore determined prevalence and prognostic impact of prior cancer among these patients. MATERIALS AND METHODS: We identified patients>65years of age diagnosed 1992-2009 with locally advanced lung cancer in the Surveillance, Epidemiology, and End Results-Medicare linked dataset. We characterized prior cancer by prevalence, type, stage, and timing. We compared all-cause and lung cancer-specific survival between patients with and without prior cancer using propensity score-adjusted Cox regression. RESULTS: 51,542 locally advanced lung cancer patients were included; 15.8% had a history of prior cancer. Prostate (25%), gastrointestinal (17%), breast (16%), and other genitourinary (15%) were the most common types of prior cancer, and 76% percent of prior cancers were localized or in situ stage. Approximately half (54%) of prior cancers were diagnosed within 5 years of the index lung cancer date. Patients with prior cancer had similar (propensity-score adjusted hazard ratio [HR] 0.96; 95% CI, 0.94-0.99; P=0.005) and improved lung cancer-specific (HR 0.84; 95% CI, 0.81-0.86; P<0.001) survival compared to patients with no prior cancer. CONCLUSIONS: For patients with locally advanced lung cancer, prior cancer does not adversely impact clinical outcomes. Patients with locally advanced lung cancer and a history of prior cancer should not be excluded from clinical trials, and should be offered aggressive, potentially curative therapies if otherwise appropriate.

Myelodysplastic syndromes following therapy with hypomethylating agents (HMAs): development of acute erythroleukemia may not influence assessment of treatment response.

This study followed 28 patients with myelodysplastic syndromes (MDS) who showed a rise of bone marrow (BM) erythroids to ≥ 50% following three cycles (1-60) of hypomethylating agent (HMA) therapy. If BM blasts were calculated as a percentage of non-erythroids, 12 (42.9%) patients met the diagnostic criteria for acute erythroleukemia, erythroid/myeloid (AEL). However, none of the patients showed clonal cytogenetic evolution or new mutations. When compared to 47 de novo AEL patients, these 12 patients were less anemic and thrombocytopenic, had less complex karyotypes (p = 0.044) and showed a longer survival, either calculated from diagnosis (p < 0.001) or from the time of AEL (p = 0.005). These findings illustrate that ≥ 50% erythroids may appear in BM post-HMA therapy, likely a combination of reduction of BM granulocytes (p < 0.001) and promotion of normal or abnormal erythroid proliferation. Enumeration of blasts as a percentage of non-erythroid cells may lead to a diagnosis of AEL and mis-interpretation as disease progression.

Correlation between mutational status and survival and second cancer risk assessment in patients with gastrointestinal stromal tumors: a population-based study.

BACKGROUND: Gastrointestinal stromal tumors are sarcomas of the digestive tract characterized by mutations mainly located in the c-KIT or in the platelet-derived growth factor receptor (PDGFR)-alpha genes. Mutations in the BRAF gene have also been described. Our purpose is to define the distribution of c-KIT, PDGFR and BRAF mutations in a population-based cohort of gastrointestinal stromal tumors (GIST) patients and correlate them with anatomical site, risk classification and survival. In addition, as most of the GIST patients have a long survival, second cancers are frequently diagnosed in them. We performed a second primary cancer risk assessment. METHODS: Our analysis was based on data from Tarragona and Girona Cancer Registries. We identified all GIST diagnosed from 1996 to 2006 and performed a mutational analysis of those in which paraffin-embedded tissue was obtained. Observed (OS) and relative survival (RS) were calculated according to risk classifications and mutational status. Multivariate analysis of variables for observed survival and was also done. RESULTS: A total of 132 GIST cases were found and we analyzed mutations in 108 cases. We obtained 53.7% of mutations in exon 11 and 7.4% in exon 9 of c-KIT gene; 12% in exon 18 and 1.9% in exon 12 of PDGFR gene and 25% of cases were wild type GIST. Patients with mutations in exon 11 of the c-KIT gene had a 5-year OS and RS of 59.6% and 66.3%, respectively. Patients with mutations in exon 18 of the PDGFR gene had a 5-year OS and RS of 84.6% and 89.7%. In multivariate analysis, only age and risk group achieved statistical significance for observed survival. GIST patients had an increased risk of second cancer with a hazard ratio of 2.47. CONCLUSIONS: This population-based study shows a spectrum of mutations in the c-KIT and PDGFR genes in GIST patients similar to that previously published. The OS and RS of GIST with the exon 18 PDGFR gene mutation could indicate that this subgroup of patients may be less aggressive and have a good prognosis, although less sensitive to treatment at recurrence. In our study, GIST patients have an increased risk of developing a second neoplasm.

Sociodemographic disparities in differentiated thyroid cancer survival among adolescents and young adults in California.

BACKGROUND: Few studies have focused on prognostic factors among adolescents and young adults (AYAs) 15 to 39 years of age when diagnosed with differentiated thyroid cancer (DTC). Our study expands upon prior work by including an evaluation of survival among AYA men and by neighborhood socioeconomic status, health insurance, and clinical factors to identify subgroups of young DTC patients at higher risk of mortality. METHODS: Data for 16,827 AYA DTC patients diagnosed between 1988 and 2010 were obtained from the California Cancer Registry. Survival, through 2010, by sociodemographic and clinical factors was analyzed using Cox proportional hazards regression. RESULTS: Of the 2.1% of AYAs who died, 16.7% died from thyroid cancer and 21.4% died from a subsequent cancer. In multivariate analyses, older AYAs 35 to 39 year of age (versus 15- to 29-year-olds), men (hazard ratio [HR] 2.77, 95% confidence interval [CI] 1.62-4.72), and AYAs of African American or Hispanic race/ethnicity (versus non-Hispanic whites) had worse thyroid cancer specific survival. In addition, residing in low socioeconomic status neighborhoods (HR 3.11 [CI 1.28-7.56]) and nonmetropolitan areas (HR 5.53 [CI 2.07-14.78]) was associated with worse thyroid cancer-specific survival among AYA men, but not AYA women. CONCLUSIONS: Despite the generally good prognosis among AYAs with DTC, we identified subgroups of AYA patients at risk for poor outcomes. Further study of the factors underlying these associations, including possible barriers to receiving high-quality treatment and follow-up care, as well as lifestyle factors, are critical to reducing these disparities.

Polycythemia vera disease burden: contributing factors, impact on quality of life, and emerging treatment options.

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by clonal expansion of a hematopoietic progenitor, erythrocytosis, often leukocytosis and/or thrombocytosis, and nearly always an activating mutation in Janus kinase 2 (JAK2). The PV symptom burden can be considerable, in part driven by small or large vessel thrombotic tendency, splenomegaly, fatigue, pruritus, and a chronic risk of disease transformation to myelofibrosis or acute myeloid leukemia. In addition, patients with PV have an increased risk of mortality compared with the general population that often results from cardiovascular complications or disease transformation. Further, healthcare utilization and costs are higher in patients with PV than noncancer controls. First-line therapy options for high-risk patients may effectively manage PV in some instances; however, some patients do not receive adequate benefit from current treatment options and experience a more severe disease burden as a result. This may be especially true for those patients who are resistant to or intolerant of hydroxyurea or interferon-based therapies. New treatments currently being investigated in phase 3 clinical trials may alleviate disease burden in this patient population.

Treatment of childhood acute lymphoblastic leukemia in central America: a lower-middle income countries experience.

BACKGROUND: Five Asociación de Hemato-Oncología de Centroamérica (AHOPCA) countries have used an adapted BFM-based protocol for childhood acute lymphoblastic leukemia (ALL). PROCEDURE: In the AHOPCA-ALL 2008 protocol, patients were stratified by age, white blood cell count, immunophenotype, central nervous system involvement, day 8 prednisone response, and morphologic bone marrow response to induction therapy. Patients at Standard Risk (SR) received a three-drug induction regimen, a reinduction phase, and maintenance with protracted intrathecal therapy. Those at Intermediate (IR) and High Risk (HR) received, in addition, daunorubicin during induction therapy, a consolidation phase and two or three reinduction phases respectively. RESULTS: From August 2008 through July 2012, 1,313 patients were enrolled: 353 in SR, 548 in IR, 412 in HR. During induction therapy, 3.0% of patients died, 2.7% abandoned treatment, 1.1% had resistant ALL, and 93.2% achieved morphological complete remission (CR). Deaths and abandonment in first CR occurred in 2.7% and in 7.0% of patients, respectively. The relapse rate at a median observation time of 2.1 years was 15.0%. At 3 years, the event-free survival (EFS) and overall survival (OS), with abandonment considered as an event, were 59.4% (SE 1.7) and 68.2% (SE 1.6). Three-year EFS was 68.5% (SE 3.0), 62.1% (SE 2.6), and 47.8% (SE 3.2) for SR, IR, and HR groups. Adolescents had a significantly higher relapse rate (P = 0.001). CONCLUSIONS: This experience shows that common international studies are feasible in lower-middle income countries. Toxic deaths, abandonment of treatment, and relapses remain major obstacles to the successful treatment. Alternative treatment strategies may be beneficial.

Treatment strategy for main duct intraductal papillary mucinous neoplasms of the pancreas based on the assessment of recurrence in the remnant pancreas after resection: a retrospective review.

OBJECTIVES: To clarify the recurrence pattern after resection of main duct intraductal papillary mucinous neoplasms (MD-IPMNs) using molecular analyses and determine the most adequate treatment strategy. BACKGROUND: The most appropriate resection line for MD-IPMNs remains an unresolved issue. METHODS: Medical records of 56 patients with pancreatectomy were retrospectively reviewed. Histological subtypes and Kras/GNAS mutations were assessed in patients with recurrence in the remnant pancreas. RESULTS: Forty-nine patients underwent partial pancreatectomy and 7 underwent total pancreatectomy. Thirty-six patients (64%) had malignant MD-IPMNs. Recurrence was observed in 7 of 49 patients (14%), including 6 with malignant IPMNs and 1 with pancreatic ductal adenocarcinoma, all of whom underwent remnant pancreatectomy. The cumulative disease-specific survival rate of patients with pancreatic recurrence was greater than that of patients with extrapancreatic recurrence (P < 0.001). Although the pancreatic margin status at the initial operation did not affect the pancreatic recurrence rate, all 4 recurrent IPMNs examined had histological subtypes and Kras/GNAS mutations identical to those of the initial lesions. Four patients experienced recurrence in the remnant pancreas or systemic recurrence after resection of high-grade dysplasia of MD-IPMN. Three of the 56 patients had concomitant pancreatic ductal adenocarcinomas and MD-IPMNs. CONCLUSIONS: One-step total pancreatectomy can be avoided, and remnant total pancreatectomy would lead to favorable outcomes even in patients with pancreatic recurrence, some cases of which seem to involve residual lesions. Postoperative surveillance of high-grade dysplasia should be performed as if malignant, and close attention should be paid to the occurrence of concomitant pancreatic ductal adenocarcinomas in patients with MD-IPMNs.

Changing trends in the presentation of colorectal liver metastases in a single hepatobiliary tertiary referral centre over fourteen years.

AIM: National Institute for Clinical Excellence guidelines suggest that patients who have undergone potentially curative treatment for colorectal cancer (CRC) should be followed up for 3 years. The aim of this study was to investigate whether the time to presentation with colorectal liver metastases (CRLM) has changed over time. This information, which is currently unknown, may inform future decisions regarding follow-up. METHODS: Patients presenting with metachronous isolated liver metastases between 1997 and 2011 were included. Timings of presentation with CRLM, rates of liver resection, survival data and factors associated with delayed presentation were investigated. RESULTS: 269 patients were included in the study. Those having their primary CRC resection between 1997 and 2007 presented earlier with liver metastases over time (r = -0.33, 95% CI -0.45 to -0.20). However, 26% of patients who developed CRLM did so beyond 3 years. There was no significant difference in rates of liver resections for those presenting within, or beyond, 3 years (p = 0.21). There was no significant difference in survival for those presenting with resectable CRLM within, or beyond, 3 years (Exp(b) = 0.60, 95% CI 0.28-1.28). No factors associated with late presentation were identified. CONCLUSIONS: These results suggest that CRC follow-up should be extended to 5 years. Follow-up interventions should be more frequent in the early stages reflecting the trend towards earlier presentation with CRLM. The economic implications of extending follow-up compare favourably to other NHS funded initiatives.

Management of cancer survivors in clinical and public health perspectives: current status and future challenges in Korea.

The number of cancer survivors is increasing dramatically. Many cancer survivors face lifetime risks associated with their cancer therapy, with a significant proportion at risk for serious morbidity and premature mortality. Concerns regarding the long-term physical, psychosocial, and economic effects of cancer treatment on cancer survivors and their families are increasingly being recognized and addressed by public and private sector. This article summarizes economic burden of cancer survivors, main post-treatment health problems including secondary primary cancer and comorbidities, health behaviors such as smoking, exercise and physical activity, nutrition, and psychosocial problems. Faced with various health and psychosocial problems specific to this population, several healthcare and policy models are being suggested to address these issues, including 'shared care model' and 'integrative supportive care service delivery system for cancer survivors'. More effort is needed to make the cancer survivorship agenda a reality, attended by a wide variety of stakeholders including researchers, patients, providers, and policy makers.

Outcome of azacitidine treatment in patients with therapy-related myeloid neoplasms with assessment of prognostic risk stratification models.

Azacitidine's efficacy in therapy-related myeloid neoplasms (t-MN) has not been well-studied. In our retrospective review of 84 t-MN patients treated with azacitidine, median overall survival (OS) was 14.5 months and overall response rate was 43%, including 11% complete remission, 4% marrow complete remission, and 11% partial remission. In patients who underwent allogeneic transplant (25%), median OS was 19.2 versus 12.8 months (P=0.023) for those who did not. Response rates were comparable to those reported for de novo myelodysplastic syndrome. When we analyzed outcomes according to five scoring systems, only the Global MD Anderson Risk Model predicted survival with statistical significance.

Neighborhood deprivation and clinical outcomes among head and neck cancer patients.

The unique effects of neighborhood-level economic deprivation on survival, recurrence, and second primary malignancy development were examined using adjusted Cox proportional hazards regression models among 1151 incident squamous cell carcinomas of the head and neck patients. Cancer site was examined as a potential moderator. Main analyses yielded null results; however, interaction analyses indicated poorer overall survival [HR=1.59 (1.00-2.53)] and greater second primary malignancy development [HR=2.99 (1.46-6.11)] among oropharyngeal cancer patients from highly deprived neighborhoods relative to less deprived neighborhoods. Results suggest a dual focus on individual and neighborhood risk factors could help improve clinical outcomes among oropharyngeal cancer patients.

A population-based assessment of mortality and morbidity patterns among patients with thymoma.

Thymomas are rare tumors of the mediastinum; a limited number of small studies have evaluated the outcomes in these patients. We identified 668 patients with thymoma from the Swedish Cancer Registry, and 2,719 population-based matched controls. We obtained information on autoimmunity from the nationwide inpatient/outpatient hospital discharge Registry. We constructed Kaplan-Meier curves for survival analysis, conditional regression and Cox proportional hazards models to evaluate the association between thymoma and autoimmune diseases, and standardized incidence ratios (SIRs) to evaluate the risk for second cancers following thymoma. Compared with controls, patients with benign or malignant thymoma had a poorer (p < 0.001) 5-year (79%, 53% vs. 91%), 10-year (65%, 39% vs. 78%) and 20-year (43%, 18% vs. 55%) overall survival. For thymoma patients, younger age at diagnosis and being diagnosed in recent years were associated with a better survival. Compared with controls, thymoma patients were more likely to have an autoimmune disease at some point during their lives (32.7% vs. 2.4%, respectively, p < 0.001), most frequently myasthenia gravis (24.5%), systemic lupus erythematosus (2.4%) and red cell aplasia (1.2%). Thymoma patients had twofold excess risk for second cancers compared with the general population, most notably: non-melanoma skin cancer (SIR = 10.6, 95% confidence intervals (CI) = 6.0-17.3), non-Hodgkin lymphoma (SIR = 6.8, 95% CI = 3.00-13.0), and cervical (SIR = 6.9, 95% CI = 1.4-20.1), endocrine (SIR = 4.7, 95% CI = 1.3-12.0), and prostate cancer (SIR = 3.0, 95% CI = 1.7-4.8). Despite the improved survival for thymoma patients over time, they have worse survival than controls. Thymoma patients are in need for follow-up to detect and manage autoimmune diseases and cancer.

Earlier stage at diagnosis and improved survival among Medicare HMO patients with breast cancer.

OBJECTIVE: We sought to evaluate differences in the stage at diagnosis and the survival of breast cancer patients enrolled in two different Medicare healthcare delivery systems: fee for service (FFS) and health maintenance organizations (HMO). METHODS: We used a linkage of two national databases, the Medicare database from the Centers for Medicare and Medicaid Services (CMS), and the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) program database, to evaluate differences in demographic data, stage at diagnosis, and survival in patients with breast cancers over the period 1985-2001. RESULTS: Medicare patients enrolled in HMOs were diagnosed at an earlier stage of diagnosis than FFS patients. HMO patients diagnosed with breast cancer had improved survival, and these differences remained even after controlling for potential confounders. Specifically, breast cancer patients enrolled in HMOs had 9% increased probability of survival (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.88-0.93) than their counterparts enrolled in FFS. These findings persisted even when patients had a cancer diagnosis before their breast cancer. CONCLUSIONS: Improved survival among breast cancer patients in HMOs compared with FFS is likely due to a combination of factors, including but not limited to earlier stage at the time of diagnosis.

Twenty-five-year follow-up among survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study.

Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for late effects of cancer therapy. Five-year ALL survivors (< 21 years at diagnosis; n = 5760 eligible, 4151 participants), diagnosed from 1970 to 1986 were compared with the general population and a sibling cohort (n = 3899). Cumulative mortality of 5760 5-year survivors was 13% at 25 years from diagnosis. Recurrent ALL (n = 483) and second neoplasms (SNs; n = 89) were the major causes of death. Among 185 survivors, 199 SNs occurred, 53% in the CNS. Survivors reported more multiple chronic medical conditions (CMCs; odds ratio [OR], 2.8; 95% CI, 2.4-3.2) and severe or life-threatening CMCs (OR, 3.6; 95% CI, 3.0-4.5) than siblings. Cumulative incidence of severe CMCs, including death, 25 years from diagnosis was 21.3% (95% CI, 18.2-24.4; 23.3% [95% CI, 19.4-27.2] and 13.4% [95% CI, 8.4-18.4] for irradiated and nonirradiated survivors, respectively). Survivors reported more adverse general and mental health, functional impairment, and activity limitations compared with siblings (P < .001). Rates of marriage, college graduation, employment, and health insurance were all lower compared with sibling controls (P < .001). Long-term survivors of childhood ALL exhibit excess mortality and morbidity. Survivors who received radiation therapy as part of their treatment or had a leukemia relapse are at greatest risk for adverse outcomes.

Metachronous bilateral renal cell carcinoma: risk assessment, prognosis and relevance of the primary-free interval.

PURPOSE: We evaluated the prognosis, risk factors and relevance of the primary-free interval in a large cohort with metachronous bilateral renal cell carcinoma. MATERIALS AND METHODS: We studied 120 patients with metachronous, bilateral renal cell carcinoma who were treated at 12 international academic centers. Logistic regression was performed to evaluate risk factors for contralateral metachronous renal cell carcinoma during followup. Disease specific survival was evaluated with univariate and multivariate analysis. RESULTS: Median age at diagnosis of the first and second renal cell carcinomas was 54 and 62 years, respectively. The most common histological subtype was bilateral clear cell renal cell carcinoma (89% of cases). Familial renal cell carcinoma was found in 14% of patients, von Hippel-Lindau disease was found in 4% and nonfamilial renal cell carcinoma was found in 81%. The 15-year disease specific survival rates for the first and second renal cell carcinomas were 66% and 44%, respectively. Logistic regression revealed von Hippel-Lindau disease, a family history of renal cell carcinoma, multifocal first renal cell carcinoma and young patient age as independent risk factors for contralateral renal cell carcinoma after surgery for unilateral renal cell carcinoma. A longer primary-free interval was associated with a better prognosis. When calculating disease specific survival from the diagnosis of the first renal cell carcinoma, the primary-free interval was an independent prognostic factor. CONCLUSIONS: Long-term survival rates of metachronous, bilateral renal cell carcinoma are moderate. von Hippel-Lindau disease, a family history of renal cell carcinoma, multifocal first renal cell carcinoma and young patient age are independent risk factors for contralateral renal cell carcinoma. These risk factors support close and extended abdominal surveillance following nephrectomy for unilateral renal cell carcinoma. Patients with a longer primary-free interval have a more favorable prognosis.

Supportive-expressive group therapy for women with metastatic breast cancer: survival and psychosocial outcome from a randomized controlled trial.

BACKGROUND: Mixed reports exist about the impact of supportive-expressive group therapy (SEGT) on survival. METHODS: From 485 women with advanced breast cancer recruited between 1996-2002, 227 (47%) consented and were randomized within an average 10 months of cancer recurrence in a 2:1 ratio to intervention with 1 year or more of weekly SEGT plus three classes of relaxation therapy (147 women) or to control receiving three classes of relaxation therapy (80 women). The primary outcome was survival; psychosocial well-being was appraised secondarily. Analysis was by intention-to-treat. RESULTS: SEGT did not prolong survival (median survival 24.0 months in SEGT and 18.3 in controls; univariate hazard ratio for death 0.92 [95% CI, 0.69-1.26]; multivariate hazard ratio, 1.06 [95% CI, 0.74-1.51]). Significant predictors of survival were treatment with chemotherapy and hormone therapy (p<0.001), visceral metastases (p<0.001) and advanced disease at first diagnosis (p<0.05). SEGT ameliorated and prevented new DSM-IV depressive disorders (p = 0.002), reduced hopeless-helplessness (p = 0.004), trauma symptoms (p = 0.04) and improved social functioning (p = 0.03). CONCLUSIONS: SEGT did not prolong survival. It improved quality of life, including treatment of and protection against depression.

A second malignancy is the major cause of death among thoracic squamous cell esophageal cancer patients negative for lymph node involvement.

BACKGROUND: The aim of the present study was to determine the major causes of death among esophageal cancer patients whose lymph nodes did not show metastasis at the time they received esophagectomy, and to consider strategies for improving survival rates among these patients. STUDY DESIGN: Between 1989 and 1999, 93 of our patients who underwent curative esophagectomy with extended lymph node dissection for thoracic squamous cell esophageal cancer showed no lymph node metastasis. We followed up these node-negative patients for as long as 10 years and determined the major causes of death. RESULTS: Sixty-three patients were still alive after esophagectomy, although 30 had died. Six patients died within 3 years after esophagectomy as a direct result of recurrence of their esophageal cancer; 13 died as a result of a second (extraesophageal) malignancy. Within the first 3 years, the major causes of death were recurrence (35%) and the second malignancy (35%); thereafter, the major cause was only the second malignancy (54%). There was no difference in the survival rates among patients with earlier, synchronous, or subsequent malignancies. Univariate and multivariate analyses of the 10-year survival showed the independent prognostic factors to be recurrence of esophageal cancer and development of a second malignancy, which respectively increased the risk of death 6.4 and 2.7 times. CONCLUSIONS: The major cause of reduced survival among thoracic squamous esophageal cancer patients, whose lymph nodes did not show metastasis, was a second malignancy. New strategies aimed at preventing or treating synchronous and subsequent malignancies could prolong the survival of these patients.

Decision analysis in the surgical treatment of colorectal cancer due to a mismatch repair gene defect.

BACKGROUND: In view of the high risk of developing a new primary colorectal carcinoma (CRC), subtotal colectomy rather than segmental resection or hemicolectomy is the preferred treatment in hereditary non-polyposis colorectal cancer (HNPCC) patients. Subtotal colectomy however implies a substantial decrease in quality of life. To date, colonoscopic surveillance has been shown to reduce CRC occurrence. AIMS: To compare the potential health effects in terms of life expectancy (LE) for patients undergoing subtotal colectomy or hemicolectomy for CRC. METHODS: A decision analysis (Markov) model was created. Information on the 10 year risk of CRC after subtotal colectomy (4%) and hemicolectomy (16%) and stages of CRCs detected within a two year surveillance interval (32% Dukes' A, 54% Dukes' B, and 14% Dukes' C) were derived from two cohort studies. Five year survival rates used for the different Dukes stages (A, B, and C) were 98%, 80%, and 60%, respectively. Remaining LE values were calculated for hypothetical cohorts with an age at CRC diagnosis of 27, 47, and 67 years, respectively. Remaining LE values were also calculated for patients with CRC of Dukes' stage A. RESULTS: The overall LE gain of subtotal colectomy compared with hemicolectomy at ages 27, 47, and 67 was 2.3, 1, and 0.3 years, respectively. Specifically for Dukes' stage A, this would be 3.4, 1.5, and 0.4 years. CONCLUSIONS: Unless surveillance results improve, subtotal colectomy still seems the preferred treatment for CRC in HNPCC in view of the difference in LE. For older patients, hemicolectomy may be an option as there is no appreciable difference in LE.