Recurrence Related Mortality Research Articles

Self-rated health is an independent predictor of subsequent late mortality after blood or marrow transplantation: A Blood or Marrow Transplant Survivor Study report.

The prevalence of suboptimal self-rated health (SRH) and its association with subsequent all-cause and cause-specific mortality after blood or marrow transplantation (BMT) were examined. Study participants were drawn from the multicenter Blood or Marrow Transplant Survivor Study, and included patients who were transplanted between 1974 and 2014 and had survived ≥2 years after BMT. Participants (aged ≥18 years) completed a survey at a median of 9 years from BMT, and were followed for a median of 5.6 years after survey completion. Survivors provided information on sociodemographic factors, chronic health conditions, health behaviors, and SRH (a single-item measure rated as excellent, very good, good, fair, or poor; excellent, very good, and good SRH were classified as good SRH, and fair and poor were classified as suboptimal SRH). The National Death Index Plus and Accurint databases and medical records provided vital status through December 2021. Of 3739 participants, 784 died after survey completion (21%). Overall, 879 BMT survivors (23.5%) reported suboptimal SRH. Pain, low socioeconomic status, psychological distress, lack of exercise, severe/life-threatening chronic health conditions, post-BMT relapse, obesity, smoking, and male sex were associated with suboptimal SRH. BMT survivors who reported suboptimal SRH had a 1.9-fold increased risk of all-cause mortality (95% confidence interval [CI],1.6-2.3), 1.8-fold increased risk of recurrence-related mortality (95% CI,1.4-2.5), and 1.9-fold increased risk of non-recurrence-related mortality (95% CI, 1.4-2.4) compared to those who reported good SRH. This single-item measure could help identify vulnerable subpopulations who could benefit from interventions to mitigate the risk for subsequent mortality.

Extralaryngeal Spread in Total Laryngectomy: Comparing the Need for Thyroidectomy.

Objective: At our institution, thyroid preservation during total laryngectomy (TL) varies by surgeon, offering a distinctive dataset to compare disease outcomes in TL patients with or without thyroidectomy. Methods: This retrospective chart review study, conducted at a tertiary referral medical center, comprises patients who underwent TL for laryngeal or hypopharyngeal squamous cell carcinoma from 2014 to 2022. The study includes data on patient demographics, surgeries, pathological staging, tumor subsites, thyroid involvement, and adjuvant therapy. Results: In this study, 147 patients, mostly male (83%) and white (82%), were included. Surgeries comprised 60 hemi thyroidectomies, 35 total or completion thyroidectomies, 48 without thyroid removal, and 4 isthmusectomies. Data analysis compared these 4 groups and the cohort of no thyroid removal (NT) versus any thyroidectomy (T = 99). Among the 99 patients, 27 showed positive gland involvement, primarily due to direct disease extension (26 cases). No significant difference was found in recurrence rates or recurrence-related mortality among the 4 groups or between NT and T (P = .156). However, there was a significant difference in T staging and prognostic staging among the groups and between NT versus T (P = .043). The NT cohort showed a higher likelihood of being T3, while T was more likely to be T4. Conclusion: We found no significant difference in recurrence rates or mortality between TL patients with or without thyroid removal. However, those without thyroid removal often had lower T stages. Notably, 27% of thyroidectomy patients had gland invasion, highlighting the importance of thyroid removal in TL.

Long-term outcomes following successful endoscopic treatment of T1 esophageal adenocarcinoma: a multicenter cohort study

Endoscopic eradication therapy (EET) is guideline endorsed for management of early-stage (T1) esophageal adenocarcinoma (EAC). Patients with baseline high grade dysplasia (HGD) and EAC are at highest risk of recurrence following successful EET, but limited data exist on long-term (> 5 year) recurrence outcomes. We aimed to assess the incidence and predictors of long-term recurrence in a multicenter cohort of T1EAC patients treated with EET. Patients with T1 EAC achieving successful endoscopic cancer eradication with a minimum of 5-years clinical follow-up were included. The primary outcome was neoplastic recurrence, defined as dysplasia or EAC, and was characterized as early (<2 years), intermediate (2-5 years), or late (>5 years). Predictors of recurrence were assessed by time to event analysis. 84 T1 EAC patients (75 T1a, 9 T1b) with a median 9.1 years (range 5.1-18.3 years) of follow-up were included. The overall incidence of neoplastic recurrence was 2.0/100 patient years of follow up. 7 recurrences (3 dysplasia, 4 EAC) occurred after 5 years of EAC remission. 88% of recurrences were treated successfully endoscopically. EAC recurrence-related mortality occurred in 3 patients at a median of 5.2 years from EAC remission. Complete eradication of intestinal metaplasia (CE-IM) was independently associated with reduced recurrence (HR 0.13). Following successful EET of T1 EAC, neoplastic recurrence occurred after 5 years in 8.3% of cases. Careful long-term surveillance should be continued in this patient population. CE-IM should be the therapeutic endpoint for EET.

Late Mortality in Childhood Cancer Survivors according to Pediatric Cancer Diagnosis and Treatment Era in the Dutch LATER Cohort

This multi-center cohort-study examined late mortality among 6,165 Dutch five-year childhood cancer survivors diagnosed 1963–2001. Clinical details and cause of death were based on medical records. Mortality was 12-fold that of the general population, with 51.3 additional deaths per 10,000 person-years (21.9 yrs median follow-up). Cumulative mortality 15 yrs post-diagnosis was 6.9%, predominantly from late recurrences; thereafter the absolute contribution of other health outcomes increased. Cumulative all-cause and recurrence-related mortality were highest for Central Nervous System and bone tumor survivors. All-cause, but not subsequent tumor and circulatory disease-related cumulative mortality, was highest for patients diagnosed 1963–1979 vs. later (p-trend <0.001).

PATTERNS OF MYOINVASION IN ENDOMETRIOID ADENOCARCINOMA OF ENDOMETRIUM

Objective: To assess the patterns of myoinvasion of endometrial endometrioid adenocarcinoma, their frequencies in our hospital and to correlate these patterns with survival.&#x0D; Study Design: Retrospective observational study.&#x0D; Place and Duration of Study: Department of Pathology, Shaukat Khanum Memorial Cancer Hospital &amp; Research Centre, Lahore, from Aug 2019 to Apr 2020.&#x0D; Methodology: All cases of endometrial endometrioid adenocarcinoma between 2015 and 2017 were retrieved from the archives, independently reviewed by two researchers, all key reporting parameters recorded in addition to the pattern of myoinvasion as per their operational definitions described by Cole and Quick. The follow-up of 3-5 years was obtained from archives and through telephonic contact for outside hospital patients. Disease free survival and relapse-associated mortality were represented through Kaplan-Meier curves.&#x0D; Results: Eighty cases of myoinvasive endometrial endometrioid adenocarcinoma were reviewed. We found that infiltrating irregular gland pattern was the most frequent in all the age groups. Thirty-five (43.75%) cases showed this type of invasion, followed by broad front pattern 23 (28.75%), Microcystic Elongated and Fragmented (MELF) pattern 15 (18.75%) and adenomyotic pattern 6 (7.5%). One case showed a combination of the last two patterns, whereas adenoma malignum pattern was not seen. Follow-up of these patients showed 8 (10%) patients with relapse related mortality including 5 (62.5%) infiltrating irregular glands, 2 (25%) adenomyosis-like and 1 (12.5%) broad front pattern of myoinvasion. Seventy-two (90%) patients had recurrence free survival.&#x0D; Conclusion: Frequency of infiltrating irregular pattern of myoinvasion in endometrial endometrioid adenocarcinoma is high and associated with recurrence related mortality. Recognition....................

Abstract 10173: Risk Factors of Cardiovascular Disease in Breast Cancer Patients

Introduction: Cardiovascular disease (CVD) events during cancer treatment can interfere with the delivery of curative therapy. In adult cancer survivors, CVD mortality is second only to cancer recurrence related mortality. We evaluated the demographic and clinical risk factors of CVD in breast cancer patients. Methods: A retrospective cohort study was conducted at Kaiser Permanente Southern California (KPSC) health system. We identified adult members (18+) diagnosed with primary breast cancer from 01/2000-12/2019 using the KPSC cancer registry. We only included patient who had at least one year of continuous health plan enrollment prior to their cancer diagnosis to determine risk factors status and to ensure they did not have any history of CVD (defined as cardiac arrest, cardiomyopathy, congestive heart failure, coronary atherosclerosis, heart valve disorders, myocardial infarction, ventricular fibrillation, dysrhythmias or stroke) prior to their cancer diagnosis. We evaluated the association of age at cancer diagnosis; race; ethnicity; obesity; cancer stage; and history of depression, drug abuse, renal failure, liver disease, lipid disorder, diabetes and hypertension using a proportional hazard model. All patients were followed from their cancer diagnosis to the earliest date of CVD (failure event) diagnosis or death or health plan disenrollment or end of study (12/2020). Results: In the cohort of 36,840 patients (Table 1), 11,993 (33%) had a CVD diagnosis during follow-up (average follow-up 5.3 years). The hazard rate of CVD increased significantly with age. Distant metastatic disease was associated with 7-fold higher CVD hazard as compared to in-situ cancer. Most other clinical factors significantly increased the hazard rate (Table 1). Conclusions: In breast cancer patients naïve to CVD disease prior to cancer diagnosis, the hazard rate of CVD post cancer diagnosis is significantly higher in older individuals and those with metastatic disease.

Trends in Late Mortality and Life Expectancy after Autologous Blood or Marrow Transplantation (BMT) Performed over Three Decades - a BMT Survivor Study (BMTSS) Report

Background: Advances in therapeutic and supportive care strategies have led to increasing use of autologous BMT to ensure durable disease-free survival in patients with hematologic malignancies. However, autologous BMT recipients carry a high burden of morbidity. The cumulative effect of autologous BMT and the long-term morbidity on life expectancy remains unknown. Further, the impact of changes in transplant practice (older age at BMT, increasing proportion of patients undergoing autologous BMT for plasma cell dyscrasias [PCD], increasing use of peripheral blood stem cells [PBSCs] and decreasing use of total body irradiation [TBI]) on late mortality and life expectancy remains unknown. We determined trends in life expectancy and cause-specific late mortality after autologous BMT performed over a 33y period (1981-2014) using the resources offered by BMTSS - a multi-institutional collaborative designed to examine late morbidity and mortality after BMT.Methods: This retrospective cohort included 4,702 individuals who lived ≥2y after autologous BMT performed between 1981 and 2014 at three transplant centers. We examined trends in life expectancy and late mortality over four eras: 1981-1999; 2000-2005; 2006-2010; 2011-2014. Endpoints included all-cause, recurrence-related mortality (RRM) and non-recurrence-related mortality (NRM) and projected reduction in life expectancy. Information on vital status and cause of death was obtained from National Death Index (NDI) Plus program and Accurinct databases. End of follow-up was 04/19/2021.Results: Median age at BMT was 53y (range, 0-78); 58.7% were male, 67.8% non-Hispanic white. Median follow up after BMT was 9y (range, 2-36). PCD was the most common indication for autologous BMT (42.3%). PBSCs were used for 91.6% of the transplants and TBI was used for conditioning in 23.1% of the patients. Across the four eras, the median age at BMT increased (40y→58y), as did the proportion of patients receiving autologous BMT for PCD (13.7%→60.0%) and the proportion of patients receiving PBSCs as the stem cell source (66.6%→99.5%). There was a dramatic decline in the proportion of patients conditioned with TBI (56.4%→5.2%), and those transplanted for acute myeloid leukemia/ myelodysplastic syndrome (AML/MDS) (15.4%→0.2%). Conditional on surviving ≥2y after autologous BMT, patients experienced a 25.8% reduction in life expectancy, representing 7.0y of life lost. In an analysis adjusted for all relevant demographic and clinical predictors and restricted to 5y of follow-up, the years of life lost declined across the four eras from 5y to 1.6y (Fig 1) The adjusted hazard of all-cause mortality also declined over the four eras (reference: 1981-1999; hazard ratio [HR]2000-2005=0.77; 95%CI=0.7-0.9; HR 2006-2010=0.62; 95%CI=0.5-0.7; HR 2011-2014=0.5; 95%CI=0.4-0.6; P trend <0.0001) (Fig 2). Mediation analysis revealed that the reduction in late mortality was evident among those transplanted for Hodgkin lymphoma (HL) or PCD, and among those who did not receive TBI . The 30y cumulative incidence of NRM (29.2%) was higher than that RRM (23.8%) (Fig 3). The adjusted hazard of RRM declined over the four eras (reference: 1981-1999; HR 2011-2014=0.55; 95%CI=0.4-0.7, P trend: <0.0001). Cause-specific late mortality declined for mortality related to infection (P trend <0.0001), subsequent malignant neoplasms (P trend=0.01), cardiovascular disease (P trend=0.001), and renal disease (P trend=0.0002), but not for pulmonary disease (P trend=0.3).Conclusions and Relevance: Late mortality among autologous BMT recipients has declined over a 30y period, likely due to changes in transplant practice (reduction in use of TBI) and improvement in disease-specific therapeutic strategies (newer therapeutic options for PCD and reduction in dose/volume of radiation for HL). Continued efforts need to focus on mitigation strategies for disease recurrence, subsequent neoplasms, infections, and cardiovascular, renal and pulmonary disease in this population. [Display omitted] DisclosuresArora: Kadmom: Research Funding; Pharmacyclics: Research Funding; Syndax: Research Funding. Forman: Allogene: Consultancy; Lixte Biotechnology: Consultancy, Current holder of individual stocks in a privately-held company; Mustang Bio: Consultancy, Current holder of individual stocks in a privately-held company. Weisdorf: Incyte: Research Funding; Fate Therapeutics: Research Funding.

Trends in Late Mortality and Life Expectancy After Allogeneic Blood or Marrow Transplantation Over 4 Decades

The past 4 decades have seen substantial changes in allogeneic blood or marrow transplantation (BMT) practice, with the overarching goal of expanding the eligible patient pool while optimizing disease-free survival. To determine trends in life expectancy and cause-specific late mortality after allogeneic BMT performed over a 40-year period. A retrospective cohort study of 4741 individuals who lived 2 or more years after allogeneic BMT performed between January 1, 1974, and December 31, 2014, was conducted at City of Hope, University of Minnesota, or University of Alabama at Birmingham. The end of follow-up was March 23, 2020. Allogeneic BMT performed in 3 eras: 1974-1989, 1990-2004, and 2005-2014. All-cause, recurrence-related, and nonrecurrence-related mortality and projected reduction in life expectancy. Information regarding vital status and cause of death was obtained from the National Death Index Plus and Accurint databases. Of the 4741 individuals included in the study, 2735 (57.7%) were male; median age at BMT was 33 years (range, 0-75 years). The cumulative incidence of recurrence-related mortality plateaued at 10 years, reaching 12.2% (95% CI, 11.0%-13.4%) at 30 years from BMT. In contrast, the incidence of nonrecurrence-related mortality continued to increase and was 22.3% (95% CI, 20.4%-24.3%) at 30 years. Leading causes of nonrecurrence-related mortality included infection (30-year cumulative incidence, 10.7%; standardized mortality ratio [SMR], 52.0), subsequent malignant neoplasms (30-year cumulative incidence, 7.0%; SMR, 4.8), cardiovascular disease (30-year cumulative incidence, 4.6%; SMR, 4.1), and pulmonary disease (30-year cumulative incidence, 2.7%; SMR, 13.9). Compared with the general population, the relative mortality remained higher at 30 or more years after BMT (SMR, 5.4; 95% CI, 4.0-7.1). The cohort experienced a 20.8% reduction in life expectancy (8.7 years of life lost). Compared with 1974-1989 (reference), the adjusted 10-year hazard ratio (HR) of all-cause mortality declined over the 3 eras (1990-2004: HR, 0.67; 95% CI, 0.53-0.85; 2005-2014: HR, 0.52; 95% CI, 0.39-0.69; P < .001 for trend), as did years of life lost (1974-1989: 9.9 years [reference]; 1990-2004: 6.5 years; and 2005-2014: 4.2 years). The reduction in late mortality was most pronounced among individuals who underwent transplantation at ages younger than 18 years (1990-2004: HR, 0.62; 95% CI, 0.40-0.96; 2005-2014: HR, 0.30; 95% CI, 0.16-0.54; reference: 1974-1989; P < .001 for trend) and those who received bone marrow (1990-2004: HR, 0.70; 95% CI, 0.54-0.90; 2005-2014: HR, 0.45; 95% CI, 0.29-0.69; reference: 1974-1989; P < .001 for trend). This cohort study noted that late mortality among recipients of allogeneic BMT has decreased over the past 40 years; however, life expectancy was not restored to expected rates compared with the general US population. Furthermore, the reduction in risk of late mortality appeared to be confined to those who underwent transplantation at a younger age or those who received bone marrow. Further efforts to mitigate disease recurrence, infections, subsequent neoplasms, cardiovascular disease, and pulmonary disease may be useful in this population.

Late morbidity and mortality among survivors of neuroblastoma treated with contemporary therapy: A report from the Childhood Cancer Survivor Study.

10044 Background: Survival rates for neuroblastoma vary widely based on risk group. Therapies have evolved over the past four decades to de-intensify treatment for individuals with low/intermediate risk disease and intensify therapy for those with high risk disease. Risk stratification is predicted to result in differential outcomes in late morbidity and mortality; the magnitude of these differences has not been well studied. Methods: We evaluated late mortality, subsequent malignant neoplasms (SMN) and chronic health conditions (CHC) graded according to CTCAE v4.03 among 491 5-year CCSS survivors of neuroblastoma diagnosed 1987-1999 at ≥1 year of age. Using age, stage at diagnosis, and treatment, survivors were classified into risk groups (low [n=182]; intermediate [n=70]; high [n=239]). Standardized mortality ratios (SMR) and standardized incidence ratios (SIR) of SMN were calculated using rates from NCHS and SEER, respectively. Cox regression models estimated hazard ratios (HR) and 95% confidence intervals (CI) for CHC compared to 1,029 CCSS siblings. Results: Among survivors (48% male; median age 22 years, range 7-42; median follow-up 19 years, range 5-29), 80.4% with low risk disease were treated with surgery alone, while 77.8% with high risk disease received surgery, radiation, chemotherapy ± transplant. The 15-year cumulative incidence of all-cause mortality was 9.2% (CI: 7.1-11.4), with a recurrence-related mortality of 7.3% (CI: 5.3-9.3) and SMN-related mortality of 0.3% (CI: 0-0.7). All-cause mortality was significantly higher in all risk groups: (low, SMR=5.8 [CI: 2.6-13.0]; intermediate, SMR=5.7 [CI: 1.4-23.5]; high, SMR=38.6 [CI: 27.9-53.5]). The risk of SMN was elevated among high risk survivors (SIR=25.1, CI: 16.7-37.6), but did not differ from the US population for survivors of low or intermediate risk disease. Table describes the HR of CHCs (grades 1-5 and 3-5) in survivors, by risk group, as compared with siblings, as well as categories of CHCs for which survivors were at increased risk. Conclusions: Long-term survivors of neuroblastoma have a high risk of late morbidity and mortality; risk is particularly pronounced among survivors of high risk disease. Vigilant lifelong medical surveillance will be required for this relatively young population as they age.[Table: see text]

The strategy and efficacy of prophylaxis against hepatitis B virus recurrence after liver transplantation for HBV-related diseases in the era of potent nucleos(t)ide analogues: A meta-analysis.

This meta-analysis aimed to evaluate the clinical outcome of liver transplant (LT) recipients under potent nucleoside or nucleotide analogue (NA)-based regimens and investigate different prophylactic schemes. We followed PRISMA statement to conduct this study. Two reviewers independently searched relevant literature via PubMed, Embase, Ovid MEDLINE, Web of Science and Insightmeme. Studies were included if they evaluated hepatitis B virus (HBV) recurrence under potent NA-based regimens in patients who received HBV-related LT. Primary and secondary outcomes were HBV recurrence, hepatocellular carcinoma (HCC) recurrence, all-cause and HBV recurrence-related mortality. Incidences with 95% confidence intervals were calculated and assessed by fixed and random effects models. Subgroup analyses were used to examine the impact of different treatment strategies. Altogether 25 studies (N = 2327) were included, with a pooled HBV recurrence rate of 1.01% (95% CI 0.53%-1.59%). HBV viremia or hepatitis D virus superinfection did not influence HBV recurrence significantly (P = 0.23 and 0.71, respectively). The recurrence rate under an indefinite combination of potent NA and hepatitis B immunoglobulin (HBIG) was lower than that under potent NA monotherapy (P = 0.000) and similar to that under NA plus a finite course of HBIG (P = 0.48). The pooled HCC recurrence rate was 5.34% (95% CI 0.78%-12.48%). HBV recurrence-related mortality and all-cause mortality were 0% and 6.95% (95% CI 4.30%-10.08%), respectively. Potent NA-based regimens provide satisfactory HBV antiviral prophylaxis and improve long-term outcomes for LT recipients. A finite combination of potent NA and HBIG is an alternative to life-long dual therapy.

Cause-specific mortality in survivors of adolescent and young adult cancer.

Few studies have adequately addressed long-term survival (>20years from diagnosis) among survivors of adolescent and young adult (AYA) cancers. In this retrospective, population-based cohort study in a US integrated health care system, the authors examined cause-specific mortality in 2-year survivors of AYA cancers (patients aged 15-39years who were diagnosed between 1990 and 2012; N=10,574) matched (by age, sex, and calendar year) to individuals without cancer (N=136,683) to determine whether mortality rates changed over time. Incidence rate ratios (IRRs) for mortality were estimated using multivariable Poisson regression. A multivariable Cox model was used to examine predictors of cause-specific mortality among AYA cancer survivors. Through December 31, 2014, 1352 deaths were observed among AYA cancer survivors, yielding an overall survival rate of 78.5% at 25years after diagnosis. Overall, AYA cancer survivors were at 10.4-fold increased risk for death (95% CI, 9.7-fold to 11.2-fold increased risk for death) compared with the matched noncancer cohort, and this risk remained elevated at >20years after diagnosis (IRR, 2.9; 95% CI, 2.0-4.3). The absolute excess risk for death from any cause was 12.7 per 1000 person-years (95% CI, 11.9-13.4 per 1000 person-years). Starting at 15years after diagnosis, the incidence of second cancer-related mortality exceeded the rate of recurrence-related mortality, and similar trends were observed for deaths from other health-related conditions. The 8-year cumulative incidence of mortality declined over time (before 2000, 12.6%; 2000-2006, 10.1%; after 2006, 7.3%; P<.001), largely because of declines in recurrence-related mortality. Age, sex, race/ethnicity, cancer stage at diagnosis, and cancer treatment predicted cause-specific mortality. The current data highlight the need for specialized, long-term follow-up care for AYA cancer survivors.

Clinical Analysis of Efficacy and Prognosis in 300 Cases of Hematological Malignancies Receiving Allogeneic Hematopoietic Stem Cell Transplantation

To investigate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of malignant hematopathy and its influencing factors. The clinical data of 300 cases received hematopoietic stem cell transplantation due to malignant hematological diseases in Zhu Jiang Hospital of Southern Medical University from January 2010 to June 2018 were analyzed retrospectively, and the factors affecting hematopoietic reconstruction, disease-free survival (DFS) and overall survival (OS) were compared between haploidentical HSCT and HLA matched HSCT. The hematopoietic reconstitution rate, incidence of GVHD, posttransplant recurrence rate and disease-free survival (DFS) were not statistically different between HLA-metched and haploidentical colorts. However, compared with HLA-matched HSCT group the time of platelet implantation was prolonged, the recurrence-related mortality was higher, and the overall survival (OS) rate was lower in the haploidentical HSCT group. Univariate analyses showed that non-remission before transplantation, and grade Ⅲ, Ⅳ aGVHD were the risk factors for OS in both groups (P＜0.05). The age than 40 years old at the time of transplantation and unrelated donors were risk factors for OS in haploidentical HSCT group (P＜0.05). Multivariate analysis showed that non-remission before transplantation and grade Ⅲ, Ⅳ aGVHD were independent prognostic indictor for OS with relative risk (RR) of 4.4 (95% CI,1.5-13.4), 9.3 (95% CI,2.3-37.0), 11.0 (95% CI,3.2-37.3) (P＜0.05) in HLA-matched HSCT group. Unrelated donor, high-risk group, and gradeⅣaGVHD were independent prognostic indictors for OS with relative risk (RR) of 7.4 (95% CI,2.3-23.1), 2.4 (95% CI,1.3-4.5), 4.1(95% CI,1.6-10.5) (P＜0.05) in haploidentical HSCT group. The comprehensive curative effect of HLA-matched HSCT is better than the haploidentical HSCT in hematological malignancies. In haploidentical HSCT the selecting related donor is better than unrelated donors, which required more platelet transfusion support.

Late Morbidity and Mortality Among Medulloblastoma Survivors Diagnosed Across Three Decades: A Report From the Childhood Cancer Survivor Study.

Treatment of medulloblastoma has evolved from surgery and radiotherapy to contemporary multimodal regimens. However, the impact on long-term health outcomes remains unknown. Cumulative incidence of late mortality (5 or more years from diagnosis), subsequent neoplasms (SNs), and chronic health conditions were evaluated in the Childhood Cancer Survivor Study among 5-year survivors of medulloblastoma diagnosed between 1970 and 1999. Outcomes were evaluated by treatment exposure, including historical therapy (craniospinal irradiation [CSI] ≥ 30 Gy, no chemotherapy), high risk (CSI ≥ 30 Gy + chemotherapy), standard risk (CSI < 30 Gy + chemotherapy), and by treatment decade (1970s, 1980s, 1990s). Rate ratios (RRs) and 95% CIs estimated long-term outcomes using multivariable piecewise exponential models. Among 1,311 eligible survivors (median age, 29 years [range, 6 to 60 years]; median time from diagnosis, 21 years [range, 5 to 44 years]), the 15-year cumulative incidence rate of all-cause late mortality was 23.2% (diagnosed 1970s) versus 12.8% (1990s; P = .002), with a recurrence-related mortality rate of 17.7% versus 9.6% ( P = .008). Lower late mortality rates as a result of other health-related causes were not observed. Among 997 survivors who completed a baseline survey, the 15-year cumulative incidence of SNs was higher among survivors with multimodal therapy (standard risk, 9.5%; historical, 2.8%; P = .03). Survivors treated in the 1990s had a higher cumulative incidence of severe, disabling, life-threatening, and fatal chronic health conditions (56.5% in 1990s v 39.9% in 1970s; P < .001) and were more likely to develop multiple conditions (RR, 2.89; 95% CI, 1.31 to 6.38). However, survivors of standard-risk therapy were less likely to use special education services than high-risk therapy survivors (RR, 0.84; 95% CI, 0.75 to 0.93). Historical changes in medulloblastoma therapy that improved 5-year survival have increased the risk for SNs and debilitating health conditions for survivors yet reduced the need for special education services.

Sirolimus in Liver Transplant Recipients with Hepatocellular Carcinoma: An Updated Meta-Analysis

ABSTRACTPrevious studies have indicated that sirolimus (SRL) may be effective for HCC patients undergoing liver transplantation (LT). However, the following results are still contradictory and do not have a clear conclusion. Therefore, we conducted an updated meta-analysis by retrieving published data in EMBASE, PubMed, and the Cochrane Library up to October 2017. Both efficiency and safety of SRL were analyzed using pooled odds ratio (ORs) with 95% confidence interval (CIs). A total of 11 studies involving 7,695 HCC patients were included. Compared with control group, SRL prolonged 1-year (OR = 2.44; CI = 1.66–3.59), 3 year (OR = 1.67; CI = 1.08–2.58) and 5-year (OR = 1.68; CI = 1.21–2.33) overall survival, as well as 1-year (OR = 2.13; CI = 1.19–3.81) disease-free survival. Pooled results found that SRL-treated patients had lower recurrence (OR = 0.60; CI = 0.37–0.98), lower recurrence-related mortality (OR = 0.58; CI = 0.42–0.81) and lower overall mortality (OR = 0.62; CI = 0.44–0.89). Moreover, fewer SRL-treated patients suffered from portal vein thrombosis (OR = 0.29; CI, 0.09–0.91) and diabetes (OR = 0.23; CI = 0.12–0.47), while SRL-treated patients were more vulnerable to acne compared with the control group (OR = 4.44; CI = 1.56–12.60). No significant differences in other adverse effects were found between two groups. Taken together, SRL-based immunosuppression is safe and effective in improving survival, as well as reducing recurrence and mortality for HCC patients following LT.

Long-term mortality and recurrence in patients treated for colonic diverticulitis with abscess formation: a nationwide register-based cohort study.

The study aimed to investigate long-term mortality, recurrence, and death related to recurrence for patients admitted with acute diverticulitis with abscess formation (Hinchey stage Ib-II). The cohort was identified by linking administrative registers for all Danish citizens in years 2000-2012. Patients were identified from ICD-10 discharge codes and stratified according to treatment (antibiotics, percutaneous abscess drainage, or surgery). From 6,641,672 persons, 3148 patients were identified with acute diverticulitis with abscess formation. Survival was comparable between treatment groups with a 1-year survival of 81-83% and a 5-year survival of 66-67% (p = 0.66). Glucocorticoid usage prior to admission increased risk of mortality with hazard ratio 1.64 (95%CI 1.39-1.93), 1.77 (1.20-2.63), and 1.92 (1.07-3.44) for the antibiotics, drainage, and operative treatment group, respectively. Drainage treatment increased risk of recurrence with sub-distribution hazard (SDH) of 1.52 (1.19-1.95) and operative treatment decreased risk with a SDH of 0.55 (0.32-0.93), both compared with antibiotic treatment (p = 0.0001). Recurrence occurred in 23.6% (18.5-30.1%) of patients in the drainage group, 15.5% (13.9-17.3%) in the antibiotics group, and 9.1% (5.1-16.1%) in the operative group. Recurrence-related mortality was 2.0% (0.9-4.4%) for the drainage group, 1.1% (0.7-1.8%) for the antibiotics group, and 0.6% (0.1-4.3%) for the operative group (p = 0.24). Most recurrences and recurrence-related mortality occurred within the first year after primary admission. This study with complete national data revealed a high mortality and recurrence rate after diverticular abscesses. Survival was comparable between treatment groups, but patients treated with drainage had significantly higher risk of recurrence.

Temporal trends in late-onset morbidity and mortality after medulloblastoma diagnosed across three decades: A report from the Childhood Cancer Survivor Study (CCSS).

10516 Background: Therapy for medulloblastoma and primitive neuroectodermal tumor has evolved from surgery and adjuvant radiotherapy to risk-adapted multimodal regimens. The impact of these changes in treatment on long-term outcomes remains unknown. Methods: Cumulative incidence of late mortality ( &gt; 5 years from diagnosis), subsequent malignant neoplasms (SMN), chronic health conditions and psychosocial functioning were evaluated among 5-year survivors in CCSS diagnosed between 1970 and 1999. Survivors were stratified according to treatment decade (1970s, 1980s, 1990s) and treatment exposure (surgery + craniospinal irradiation [CSI] ≥30 Gy, no chemotherapy; surgery + CSI ≥30 Gy + chemotherapy [high-risk therapy], surgery + CSI ˂30 Gy + chemotherapy [standard-risk therapy]). Rate ratios (RRs), odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for long-term outcomes among treatment eras and exposure groups using multivariable piecewise-exponential models. Results: Among 1,380 eligible survivors (median [range] age 29 [6-20] years; 21.4 [5-44] years from diagnosis), the 15-year cumulative incidence of all-cause (21.9% 1970s vs. 12.8% 1990s; p = 0.003) and recurrence-related (16.2% vs 9.6%, p = 0.03) late mortality decreased with no reduction in mortality attributable to late effects of therapy including SMN. Among 959 participants, the incidence of SMN did not decrease by era or by treatment group. However, survivors treated in the 1990s had an increased cumulative incidence of severe, life-threatening and fatal health conditions (16.9% 1970s vs 25.4% 1990s; p = 0.03), and were more likely to develop multiple severe or life-threatening health conditions, RR = 2.98 (95% CI, 1.10-8.07). Survivors of standard-risk therapy were less likely to use special education services than high-risk therapy patients, OR = 0.51 (95% CI, 0.33-0.78). Conclusions: Historical changes in therapy have improved 5-year survival, reduced risk of late mortality due to disease recurrence, and reduced special education utilization, at the cost of increased risk for multiple, severe and life-threatening chronic health conditions.

A matched-pair analysis of laparoscopic versus open pancreaticoduodenectomy: oncological outcomes using Leeds Pathology Protocol

Laparoscopic pancreaticoduodenectomy (LPD) is a safe procedure. Oncological safety of LPD is still a matter for debate. This study aimed to compare the oncological outcomes, in terms of adequacy of resection and recurrence rate following LPD and open pancreaticoduodenectomy (OPD). Between November 2005 and April 2009, 12 LPDs (9 ampullary and 3 distal common bile duct tumors) were performed. A cohort of 12 OPDs were matched for age, gender, body mass index (BMI) and American Society of Anesthesiologists (ASA) score and tumor site. Mean tumor size LPD vs OPD (19.8 vs 19.2 mm, P=0.870). R0 resection was achieved in 9 LPD vs 8 OPD (P=1.000). The mean number of metastatic lymph nodes and total number resected for LPD vs OPD were 1.1 vs 2.1 (P=0.140) and 20.7 vs 18.5 (P=0.534) respectively. Clavien complications grade I/II (5 vs 8), III/IV (2 vs 6) and pancreatic leak (2 vs 1) were statistically not significant (LPD vs OPD). The mean high dependency unit (HDU) stay was longer in OPD (3.7 vs 1.4 days, P<0.001). There were 2 recurrences each in LPD and OPD (log-rank, P=0.983). Overall mortality for LPD vs OPD was 3 vs 6 (log-rank, P=0.283) and recurrence-related mortality was 2 vs 1. There was one death within 30 days in the OPD group secondary to severe sepsis and none in the LPD group. Compared to open procedure, LPD achieved a similar rate of R0 resection, lymph node harvest and long-term recurrence for tumors less than 2 cm. Though technically challenging, LPD is safe and does not compromise oncological outcome.

Meta‐analysis: recurrence and survival following the use of sirolimus in liver transplantation for hepatocellular carcinoma

The use of sirolimus (SRL)-based immunosuppression protocols have been reported to reduce recurrence rates following liver transplantation (LT) for hepatocellular carcinoma (HCC), although this is still a matter for debate. To undertake a systematic review and meta-analysis of available literature on the usage of SRL as an immunosuppressive agent following LT for HCC, with a view to comparing cancer outcomes with the commonly used calcineurin inhibitors (CNIs). Systematic review and meta-analysis carried out in line with the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. Primary outcomes of interest were tumour recurrence rate and recurrence-free survival (RFS). Secondary outcomes were recurrence-related mortality and overall survival (OS). In all, 5 studies met the inclusion criteria (n = 474). The recurrence rate was lower in SRL group (4.9-12.9%) in comparison with CNIs (17.3-38.7%). The 1-, 3- and 5-year RFS was 93-96%, 82-86% and 79-80% for SRL group, which was much better in comparison with the CNIs 70-78%, 64-65% and 54-60% respectively. Similarly, 1-, 3- and 5-year OS was much better for SRL group (94-95%, 85% and 80%) in comparison with CNIs (79-83%, 66% and 59-62%) respectively. Meta-analysis demonstrated lower recurrence (OR = 0.30, 95% CI = 0.16-0.55, P < 0.001), lower recurrence-related mortality (OR = 0.29, 95% CI = 0.12-0.70, P = 0.005) and lower overall mortality (OR = 0.35, 95% CI = 0.20-0.61, P < 0.001) for SRL group. The review showed lower recurrence rate, longer recurrence-free survival and overall survival and lower recurrence-related mortality in sirolimus-treated patients in comparison with the calcineurin inhibitor-treated patients following liver transplantation for hepatocellular carcinoma.

PMO-095 Laparoscopic vs open pancreaticoduodenectomy: oncological outcomes using leeds pathology protocol (LEEPP)—a matched-pair analysis

IntroductionLaparoscopic Pancreaticoduodenectomy (LPD) has recently been shown to be a technically safe procedure. Oncological safety of LPD is still a matter for debate. Currently, there is limited evidence for cancer...

Do the expressions of gap junction gene connexin messenger RNA in noncancerous liver remnants of patients with hepatocellular carcinoma correlate with postoperative recurrences?

To investigate whether the changes of gap junction gene connexin messenger RNA in the noncancerous liver tissue of patients with hepatocellular carcinoma (HCC) could play a significant role in its postresection recurrence. Seventy-nine consecutive patients having undergone curative resection for HCC entered this study. Using a reverse-transcription polymerase chain reaction (RT-PCR)-based assay, connexin (Cx) 26, connexin (Cx) 32 and connexin (Cx) 43 mRNAs were determined prospectively in noncancerous liver tissues from these 79 patients and in the liver tissues from 15 controls. The correlations between connexin mRNA expression and the clinicopathological variables and outcomes (tumor recurrence and recurrence related mortality) were studied. Compared with liver tissues of control patients, the expression of Cx 32 mRNA in noncancerous liver tissues was significantly lower (mean: 0.715 vs control 1.225, P<0.01), whereas the decreased Cx 26 mRNA (mean: 0.700 vs of control 1.205, P>0.05) and increased Cx 43 mRNA (mean: 0.241 vs control 0.100, P>0.05) had no statistical significance. We defined the value of Cx 32 mRNA or Cx 26 mRNA below 0.800 as a lower value. By multivariate analysis for noncancerous livers, a lower value of Cx 32 mRNA correlated significantly with a risk of HCC recurrence and recurrence-related mortality. The lower value of Cx 26 mRNA did not correlate with recurrence and mortality. The increased value of Cx43 mRNA also did not correlate with postoperative recurrence and recurrence-related mortality. By multivariate analysis, other significant predictors of HCC recurrence included vascular permeation, cellular dedifferentiation, and less encapsulation. The other significant parameter of recurrence related mortality was vascular permeation. The decreased expression of Cx 32 mRNA in noncancerous liver tissues plays a significant role in the prediction of postoperative recurrence of HCC.