Relative Survival Analysis Research Articles

A parametric approach to relaxing the independence assumption in relative survival analysis.

With known cause of death (CoD), competing risk survival methods are applicable in estimating disease-specific survival. Relative survival analysis may be used to estimate disease-specific survival when cause of death is either unknown or subject to misspecification and not reliable for practical usage. This method is popular for population-based cancer survival studies using registry data and does not require CoD information. The standard estimator is the ratio of all-cause survival in the cancer cohort group to the known expected survival from a general reference population. Disease-specific death competes with other causes of mortality, potentially creating dependence among the CoD. The standard ratio estimate is only valid when death from disease and death from other causes are independent. To relax the independence assumption, we formulate dependence using a copula-based model. Likelihood-based parametric method is used to fit the distribution of disease-specific death without CoD information, where the copula is assumed known and the distribution of other cause of mortality is derived from the reference population. We propose a sensitivity analysis, where the analysis is conducted across a range of assumed dependence structures. We demonstrate the utility of our method through simulation studies and an application to French breast cancer data.

Population-based cancer survival in the Golestan province in the northeastern part of Iran 2007–2012

ObjectiveWe studied 5-year relative survival (RS) for 14 leading cancer sites in the population-based cancer registry (PBCR) of Golestan province in the northeastern part of Iran. MethodologyWe followed patients diagnosed in 2007–2012 through data linkage with different databases, including the national causes of death registry and vital statistics office. We also followed the remaining patients through active contact. We used relative survival (RS) analysis to estimate 5-year age-standardized net survival for each cancer site. Multiple Imputation (MI) method was performed to obtain vital status for loss to follow-up (LTFU) cases. ResultsWe followed 6910 cancer patients from Golestan PBCR. However, 2162 patients were loss to follow-up. We found a higher RS in women (29.5%, 95% CI, 27.5, 31.7) than men (21.0%, 95% CI, 19.5, 22.5). The highest RS was observed for breast cancer in women (RS=49.8%, 95% CI, 42.2, 56.9) and colon cancer in men (RS=37.9%, 95% CI, 31.2, 44.6). Pancreatic cancer had the lowest RS both in men (RS= 8.7%, 95% CI, 4.1, 13.5) and women (RS= 7.9%, 95% CI, 5.0, 10.8) ConclusionAlthough the 5-year cancer survival rates were relatively low in the Golestan province, there were distinct variations by cancer site. Further studies are required to evaluate the survival trends in Golestan province over time and compare them with the rates in the neighboring provinces and other countries in the region.

Two-Year Landmark Survival Analysis after Allogeneic Hematopoietic Cell Transplantation in Acute Lymphoblastic Leukemia: An Analysis from the ALWP of the EBMT

BackgroundLong-term survival and late mortality risk compared to general population for patients (pts) who underwent an allogeneic hematopoietic cell transplant (HCT) is unknown. We analyzed long-term outcomes of 2-year (yr) HCT survivors with acute lymphoblastic leukemia (ALL).MethodsAdult pts with ALL who were alive and relapse-free at 2 yrs after first HCT from 2005-2012 were included. We excluded patients who had a cord blood transplant and ex vivo T cell depletion (TCD). Relative survival analysis was used to estimate HCT-related crude mortality taking into account for background population mortality rates of the general population, matched for age, sex, and country in the year of HCT (www.mortality.org).ResultsA total of 2701 pts were included with a median follow up interval of 99 months and median age of 34 (range 18 - 73.5) yrs. The majority (78.6%) of pts were in 1 st complete remission (CR1) with undetectable MRD (68.3%). There were similar numbers of matched sibling donor (MSD) (43.7%) and unrelated donor transplants (MUD) (53.2%). Most pts received myeloablative conditioning (MAC) (86.5%) and peripheral blood (PB) grafts (75.7%) without in vivo TCD (55.7%).The 10-yr probability for overall survival (OS) and leukemia-free survival (LFS) was 81.3% and 78.2%, respectively. Cumulative incidence of disease relapse and non-relapse mortality (NRM) at 10 years was 9.9% and 11.9%, respectively. The probability of chronic GVHD-relapse-free survival (cGRFS) at 10-yrs was 73.3% (Figure 1). Relapsed ALL and chronic GVHD were common causes of late mortality accounting for 33.9% and 29% of reported deaths, respectively, followed by infection and secondary malignancy. For patients transplanted in countries with available mortality data (92% of patients in our cohort), the probability of dying from another cause is negligible at 1.5% compared to the probability of dying from HCT (16.8%) 10 years after HCT (Figure 1F).ConclusionsIn a large registry-based study, we showed excellent long-term survival of 81.3% at 10-yr among the 2-yr survivors of HCT for ALL. There was no difference in long term outcomes with respect to conditioning intensity, but utilization of BM graft and in vivo TCD resulted in lower NRM, and better OS. Long-term mortality risk among HCT survivors remains significantly higher than expected for the general age-matched population. [Display omitted] DisclosuresLabopin: Jazz Pharmaceuticals: Honoraria. Schroeder: Celgene: Honoraria, Other: Travel support, Research Funding. Bethge: Miltenyi Biotec: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Kite-Gilead: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau. Nicholson: Pfizer: Consultancy; BMS/Celgene: Consultancy; Kite, a Gilead Company: Other: Conference fees, Speakers Bureau; Novartis: Consultancy, Other: Conference fees. Giebel: Janssen: Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau. Peric: Therakos, Servier, MSD, Astellas, Novartis, Abbvie, Pfizer: Honoraria. Dholaria: Janssen: Research Funding; Pfizer: Research Funding; Takeda: Research Funding; Jazz: Speakers Bureau; MEI: Research Funding; Angiocrine: Research Funding; Poseida: Research Funding; Celgene: Speakers Bureau. Mohty: Sanofi: Honoraria, Research Funding; Pfizer: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Jazz: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gilead: Honoraria; Celgene: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Astellas: Honoraria; Amgen: Honoraria; Adaptive Biotechnologies: Honoraria.

Sex and survival following pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension: a Scandinavian observational cohort study.

Studies have suggested sex-related survival differences in chronic thromboembolic pulmonary hypertension (CTEPH). Whether long-term prognosis differs between men and women following pulmonary endarterectomy for CTEPH remains unclear. We investigated sex-specific survival after pulmonary endarterectomy for CTEPH. We included all patients who underwent pulmonary endarterectomy for CTEPH at two Scandinavian centers and obtained baseline characteristics and vital statuses from patient charts and national health-data registers. Propensity scores and weighting were used to account for baseline differences. Flexible parametric survival models were employed to estimate the association between sex and all-cause mortality and the absolute survival differences. The expected survival in an age-, sex-, and year of surgery matched general population was obtained from the Human Mortality Database, and the relative survival was used to estimate cause-specific mortality. A total of 444 patients were included, comprising 260 (59%) men and 184 (41%) women. Unadjusted 30-day mortality was 4.2% in men versus 9.8% in women (p = 0.020). In weighted analyses, long-term survival did not differ significantly in women compared with men (hazard ratio: 1.36; 95% confidence interval: 0.89–2.06). Relative survival at 15 years conditional on 30-day survival was 94% (79%–107%) in men versus 75% (59%–88%) in women. In patients who underwent pulmonary endarterectomy for CTEPH, early mortality was higher in women compared with men. After adjustment for differences in baseline characteristics, female sex was not associated with long-term survival. However, relative survival analyses suggested that the observed survival in men was close to the expected survival in the matched general population, whereas survival in women deviated notably from the matched general population.

Abstract 741: Characterization of high-grade serous ovarian carcinoma by measuring functional signal transduction pathway activity

Abstract Introduction: The majority of advanced stage high-grade serous ovarian carcinoma (HGSC), the most common subtype of ovarian cancer, recurs within the first 24 months despite complete remission after initial treatment. Yet there are remarkable differences in disease-free (DFS) and overall survival (OS). We hypothesize that differences in signal transduction pathway (STP) activity may relate to survival and may also improve targeted therapy selection. We investigate the STP activity in relation to survival in patients diagnosed with advanced stage HGSC, as well as identify STPs that may be targeted in alternative treatment strategies. Methods: We included 85 HGSC patients (DFS <12 months, n=52 and DFS >24 months, n=33) who achieved complete remission after treatment with debulking surgery and chemotherapy. Total mRNA was extracted, and RT-qPCR was performed to determine expression levels of pathway-specific target genes in primary HGSC samples taken prior to start of chemotherapy. OncoSignal pathway assays were used to quantitatively measure functional STP activity of the androgen and estrogen receptor (ER), PI3K, Hedgehog, TGF-β and Wnt pathways. Survival analysis in relation to STP activity was performed by means of Cox regression analysis and differences between groups were analyzed with Mann-Whitney U tests. Results: Differences in PI3K, Hedgehog and TGF-β pathway activity were observed across the HGSC cohort, suggesting unique tumor activation patterns. Median STP activity was not discernably different between the short and long DFS groups. Significantly higher ER pathway activity was found in premenopausal women (n=16) compared to postmenopausal women (n=67) (p=0.002). Cox regression analysis in postmenopausal women (n=67) showed that ER pathway activity was positively associated with DFS (HR=0.943, p=0.033) and OS (HR=0.930, p=0.041) in univariate analysis. None of the pathways were significantly related to DFS or OS in premenopausal women (n=16). Conclusion: We observed a positive association between ER pathway activity and survival in postmenopausal women but not in premenopausal women. Also, differences in activation levels of the other STPs were observed in individual patients. STP analysis may be used to aid targeted therapy selection, such as anti-hormonal therapy, in HGSC patients. Citation Format: Phyllis van der Ploeg, Laura van Lieshout, Yvonne Wesseling-Rozendaal, Anja van de Stolpe, Diederick Keizer, Steven Bosch, Marjolein Lentjes-Beer, Caroline Vos, Joanne de Hullu, Ruud Bekkers, Jurgen Piek. Characterization of high-grade serous ovarian carcinoma by measuring functional signal transduction pathway activity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 741.

Favorable Long-Term Outcomes after Allogeneic Transplantation for Elderly Patients with Myelodysplastic Syndromes: A Report from the Chronic Malignancies Working Party of EBMT

Introduction: Communicating about the risk of mortality after allogeneic hematopoietic stem cell transplantation (HCT) is a challenging task for physicians. This is especially true for elderly patients with aggressive hematologic malignancies. Mortality after HCT may be split in three major parts, death after relapse, therapy-related mortality (including late complications of previous treatments of the hematologic malignancies) and background or general population mortality from causes unrelated to the treatment or disease. In the framework of the competing endpoints, relapse and non-relapse mortality, background mortality mainly determines the magnitude of non-relapse mortality. To estimate the size of the background mortality, the risk of an age-, sex-, country- and calendar year matched population can be used as approximation. This can be done with methods from relative survival analysis. By nature, background mortality increases among elderly patients. In order to study the size of background and excess mortality we analyzed mortality in a population of adult transplant recipients with myelodysplastic syndromes (MDS) because this indication is characterized by a high median age already at diagnosis and large numbers of transplanted patients.Patients and Methods: Data from adult patients with MDS who had received a first allogeneic HCT between January 2000 and December 2012, and who were registered with the EBMT database, were analyzed. Patients who had received mismatched related HCT or cord-blood transplantation were excluded from this analysis due to insufficient numbers of patients in the respective subgroups. For the statistical analysis we combined relative survival methods and multi-state modeling (Pohar M (2006) and de Wreede LC (2010), both in Computer Methods and Programs in Biomedicine). Outcomes were calculated since HCT. Outcomes of the subgroup of patients still alive and disease-free at 2 years after HCT were also analyzed to focus on the long-term prognosis of patients who had not suffered from early treatment failure.Results: In total, 6434 patients were included into the analysis. The number of transplants increased from 185 in the year 2000 to 862 in 2012. Median age at alloHCT increased from 49 years (range 18 to 70 years) in 2000 to 58 years (18-76 years) in 2012 (Wilcoxon rank sum test, p<0.001). During the same period of time the number of patients who were 65 years or older at the time of alloHCT increased from 9 (5% of all patients transplanted in 2000) to 150 (17% of all patients transplanted in 2012).The probability of overall survival (OS) decreased from 53% (95%CI, 52-55%) at two years to 43% (95%CI, 42-45%) at five years and to 35% (95%CI, 34-37%) at ten years after alloHCT. The 5-year survival probability calculated from the day of HCT was 53% (95%CI, 50-56%) for patients <45 years of age at alloHCT compared to 35% (95%CI, 32-39%) for patients above 65 years. Conversely, 5-year non-relapse mortality (NRM) was 25% (95%CI, 22-27%) and 36% (95%CI, 32-39%), for the respective age groups.At the 2-year landmark (LM) 2578 patients in the dataset were alive and disease-free. The 5-year OS probability from this LM was 88% (95%CI, 86-91%) for patients <45 years of age at alloHCT compared to 63% (95%CI, 55-71%) for patients transplanted at an age ≥65 years. The figure below shows the probability of overall survival with associated 95%CIs for patients aged ≥65 years at alloHCT who were alive and disease-free at the 2-year LM compared to the survival of the general population matched to the patient population by age, sex, country and calendar year. The cumulative incidence of NRM during the same period was 7% (95%CI, 4-9%) for patients <45 years of age compared to 25% (95%CI, 18-32%) for patients transplanted at an age ≥65 years. Notably, of the 5-year NRM calculated for the 2-year LM population of patients who were transplanted at an age ≥65 years, 35% of deaths could be contributed to background mortality.Conclusions: We show very favorable long-term outcomes after allogeneic HCT for patients with MDS. While long-term survivors of all age groups are at risk for excess mortality, the results of this study suggest that for elderly patients a substantial part of non-relapse mortality after HCT has to be attributed to background mortality. These results may help in communicating the risk of mortality after HCT especially for elderly patients in a more balanced way. [Display omitted] DisclosuresSchetelig:Sanofi Aventis: Consultancy, Research Funding; Roche: Honoraria; Abbvie: Honoraria; Janssen: Consultancy, Honoraria. Platzbecker:Acceleron: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding. Luft:Alexion: Consultancy; Neovii: Research Funding. Kobbe:Celgene: Other: Advisory Board, Research Funding.

Incidence and survival of epithelial ovarian, fallopian tube, peritoneal, and undesignated abdominal/pelvic cancers in Sweden 1960\u20132014: A population-based cohort study

BackgroundDespite improved surgical and oncological treatment, ovarian cancer continues to be the most lethal of the gynecologic malignancies. We aimed to analyze survival trends in epithelial ovarian cancer with regard to age, tumor site, and morphology in Sweden 1960 to 2014.MethodsA nationwide population-based study was conducted using data from the Swedish Cancer Registry on 46,350 women aged 18 or older with a diagnosis of epithelial ovarian, fallopian tube, peritoneal, or undesignated abdominal/pelvic cancer 1960 to 2014. Analyses of age-standardized incidence and relative survival (RS) were performed and time trends modelled according to age, tumor site, and morphology.ResultsOverall incidence of ovarian, tubal, peritoneal, and undesignated abdominal/pelvic cancers declined since 1980. Median age at diagnosis increased. Serous carcinoma increased in incidence. RS at 1, 2 and 5 years from diagnosis improved since 1960, although not for the youngest and the oldest patients. Ten-year RS did not improve. The best RS was found for fallopian tube cancer and the worst RS for undesignated abdominal/pelvic cancer. Among the morphologic subgroups, endometrioid carcinoma had the best RS.ConclusionsSurvival in epithelial ovarian, tubal, peritoneal, and undesignated abdominal/pelvic cancers in Sweden has improved over the last six decades. Advances in epithelial ovarian cancer treatment have extended life for the first 5 years from diagnosis but 10-year survival remains poor.

Socioeconomic disparities in head and neck cancer survival in Germany: a causal mediation analysis using population-based cancer registry data

PurposeDespite recent improvements in cancer treatment in Germany, a marked difference in cancer survival based on socioeconomic factors persists. We aim to quantify the effect of socioeconomic inequality on head and neck cancer (HNC) survival.MethodsInformation on 20,821 HNC patients diagnosed in 2009–2013 was routinely collected by German population-based cancer registries. Socioeconomic inequality was defined by the German Index of Socioeconomic Deprivation. The Cox proportional regression and relative survival analysis measured the survival disparity according to level of socioeconomic deprivation with respective confidence intervals (CI). A causal mediation analysis was conducted to quantify the effect of socioeconomic deprivation mediated through medical care, stage at diagnosis, and treatment on HNC survival.ResultsThe most socioeconomically deprived patients were found to have the highest hazard of dying when compared to the most affluent (Hazard Ratio: 1.25, 95% CI 1.17–1.34). The most deprived patients also had the worst 5-year age-adjusted relative survival (50.8%, 95% CI 48.5–53.0). Our mediation analysis showed that most of the effect of deprivation on survival was mediated through differential stage at diagnosis during the first 6 months after HNC diagnosis. As follow-up time increased, medical care, stage at diagnosis, and treatment played no role in mediating the effect of deprivation on survival.ConclusionThis study confirms the survival disparity between affluent and deprived HNC patients in Germany. Considering data limitations, our results suggest that, within six months after HNC diagnosis, the elimination of differences in stage at diagnosis could reduce survival inequalities.

Relative conditional survival analysis provides additional insights into the prognosis of heart failure patients

Relative conditional survival analysis provides additional insights into the prognosis of heart failure patients

To what extent has the last two decades seen significant progress in the management of older patients with head and neck cancer?

IntroductionLife expectancy is rising and consequently also the number of older patients with head and neck cancer. Different treatment regimens are often applied for older patients. The aim of this study is to investigate how treatment patterns and survival rates have changed over the past 20 years in older patients with head and neck squamous cell carcinoma (HNSCC). MaterialsPatient and tumour characteristics, treatment and 5-year survival data from the Netherlands Cancer Registry of patients aged ≥60 years diagnosed with HNSCC in 1990–1995 and 2010–2015 were compared using chi-square test and relative survival analysis. ResultsData of 14,114 patients were analyzed. Oral cavity cancer treatment did not change over time, while survival improved from 54% to 58% (p = 0.03). Oropharyngeal and hypopharyngeal cancer treatment shifted towards non-surgical, with survival improving from 31% to 51% (p < 0.01) and 26% to 34% (p < 0.01), respectively. Laryngeal cancer treatment changed towards surgery in stage I and non-surgical treatment in stage III and IV disease. Survival in laryngeal cancer stage I remained stable and favorable at a relative survival rate of around 90%. Survival non-significantly changed from 54% to 49% for stage III disease and from 37% to 33% for disease. ConclusionRelative survival increased for all head and neck cancer sites in older patients, except for laryngeal cancer. For oropharyngeal, hypopharyngeal and advanced laryngeal cancer, a shift towards non-surgical treatment modalities was observed.

Medical specialties and life expectancy: An analysis of doctors’ obituaries 1997–2019

AbstractBackgroundPrevious studies have found emergency medicine physicians have a reduced life expectancy compared to other doctors, using small subsets of data from the obituary section of the British Medical Journal. Technological advances now allow the entire catalogue of obituaries to be interrogated, which allows exploration of the relationship between medical specialty, age at death and cause of death in doctors.MethodsPublicly available electronic records were obtained by web scraping and analysed with natural language processing algorithms. Obituaries published in the British Medical Journal between January 1997 and August 2019 were scraped and analysed for differences in age and cause of death and also relative survival analysis compared to the general U.K. population.ResultsData were extracted from 8156 obituaries. The specialties with the oldest average age at death were general practitioners (80.3, SD = 12.5, n = 2508), surgeons (79.9, SD = 13.6, n = 853) and pathologists (79.8, SD = 13.8, n = 394). The specialties with the youngest average age at death were emergency physicians (58.7, SD = 23.6, n = 43), anaesthetists (75.5, SD = 16.1, n = 473) and radiologists (75.8, SD = 14.5, n = 172). Cancer was the most common cause of death and did not differ by specialty. Doctors on average have an older age at death than the general U.K. population.ConclusionsA doctor's specialty has a significant association with their age at death, with general practitioners living the longest and emergency physicians the shortest, with proportionately more accidental deaths. Likely due to its recency as a separate specialty, the emergency physician group is the smallest, which may censor and falsely reduce this group's age at death. The observed increased life expectancy and the reduced cardiovascular disease in this cohort may be associated with lifestyle and socioeconomic factors.

Medical Care and Survival of Soft-Tissue and Bone Sarcoma Patients: Results and Methodological Aspects of a German Subnational Cohort Study Based on Administrative Healthcare Data

Introduction: Medical care of soft-tissue sarcoma (STS) and bone sarcoma (BS) patients in Germany has rarely been investigated. The objectives of this article were (1) to investigate medical care and survival in STS and BS patients, and (2) to examine methodological aspects of corresponding analyses based on administrative healthcare data. Methods: We analyzed data from a statutory health insurance located in Saxony, Germany, covering approximately 2 million individuals. We identified incident STS and BS patients in the period 2012–2016 using 4 different case definitions. We examined treatment rates and visits to medical oncologists and medical practices descriptively, and then compared results between case definitions. We investigated survival prospects using a relative survival analysis and estimated hazard ratios (HRs) for risk factors for mortality using Cox regression. Results: Across case definitions, the number of included sarcoma patients (STS: n = 871–1,757; BS: n = 216–689) and applied treatments (STS: 42.2–83.1%; BS: 28.3–77.8%) varied substantially. Irrespective of the case definition, the minority of patients visited medical oncologists (STS: 9.8–10.8% BS: 4.4–7.9%) and “experienced” medical practices (STS: 27.7–38.4%; BS: 18.3–23.6%). Survival prospects were better for patients who visited “experienced” medical practices (STS: HR = 0.55; BS: HR = 0.42). Conclusion: Treatment rates clearly <100% and evidence from survival analyses indicate the potential for improvements in the care of sarcoma patients in Germany, e.g., by physicians in “experienced” medical practices.

Epidemiology of perforating peptic ulcer: A population-based retrospective study over 40 years.

BACKGROUNDThe incidence of peptic ulcer disease has decreased during the last few decades, but the incidence of reported peptic ulcer complications has not decreased. Perforating peptic ulcer (PPU) is a severe form of the disease.AIMTo assess trends in the incidence, presentation, and outcome of PPU over a period of 40 years.METHODSThis was a single-centre, retrospective, cohort study of all patients admitted to Levanger Hospital, Norway, with PPU from 1978 to 2017. The patients were identified in the Patient Administrative System of the hospital using International Classification of Diseases (ICD), revision 8, ICD-9, and ICD-10 codes for perforated gastric and duodenal ulcers. We reviewed the medical records of the patients to retrieve data. Vital statistics were available for all patients. The incidence of PPU was analysed using Poisson regression with perforated ulcer as the dependent variable, and sex, age, and calendar year from 1978 to 2017 as covariates. Relative survival analysis was performed to compare long-term survival over the four decades.RESULTSTwo hundred and nine patients were evaluated, including 113 (54%) men. Forty-six (22%) patients were older than 80 years. Median age increased from the first to the last decade (from 63 to 72 years). The incidence rate increased with increasing age, but we measured a decline in recent decades for both sexes. A significant increase in the use of acetylsalicylic acid, from 5% (2/38) to 18% (8/45), was observed during the study period. Comorbidity increased significantly over the 40 years of the study, with 22% (10/45) of the patients having an American Society of Anaesthesiologists (ASA) score 4-5 in the last decade, compared to 5% (2/38) in the first decade. Thirty-nine percent (81/209) of the patients had one or more postoperative complications. Both 100-day mortality and long-term survival were associated with ASA score, without significant variations between the decades.CONCLUSIONDeclining incidence rates occurred in recent years, but the patients were older and had more comorbidity. The ASA score was associated with both short-term mortality and long-term survival.

Ablation Therapy for Advanced Stage Non-Small Cell Lung Cancer: A National Cancer Database Study

PurposeTo compare overall survival (OS) of ablation with no treatment for patients with advanced stage non-small cell lung cancer. MethodsPatients with clinical stage IIIB (T1–4N3M0, T4N2M0) and stage IV (T1–4N0–3M1) non-small cell lung cancer, in accordance with the American Joint Committee on Cancer, 7th edition, who did not receive treatment or who received ablation as their sole primary treatment besides chemotherapy from 2004 to 2014, were identified from the National Cancer Data Base. OS was estimated using the Kaplan-Meier method and evaluated by log-rank test, univariate and multivariate Cox proportional hazard regression, and propensity score-matched analysis. Relative survival analyses comparing age- and sex-matched United States populations were performed. ResultsA total of 140,819 patients were included. The 1-, 2-, 3- and 5-year survival rates relative to age- and sex-matched United States population were 28%, 18%, 12%, and 10%, respectively, for ablation (n = 249); and 30%, 15%, 9%, and 5%, respectively for no treatment (n = 140,570). Propensity score matching resulted in 249 patients in the ablation group versus 498 patients in the no-treatment group. After matching, ablation was associated with longer OS than that in the no-treatment group (median, 5.9 vs 4.7 months, respectively; hazard ratio, 0.844; 95% confidence interval, 0.719–0.990; P = .037). These results persisted in patients with an initial tumor size of ≤3 cm. ConclusionsPreliminary results suggest ablation may be associated with longer OS in patients with late-stage non-small cell lung cancer than survival in those who received no treatment.

Non-epithelial ovarian cancer in Denmark – Incidence and survival over nearly 40 years

ObjectiveTo examine trends in incidence and survival of non-epithelial ovarian cancer in Denmark over nearly 40 years, using nationwide, population-based cancer registry data. MethodsFrom 1978 to 2016, we identified the non-epithelial ovarian cancer cases among all ovarian malignancies in the Danish Cancer Registry. Age-specific incidence rates, age-standardized incidence rates, and average annual percentage change (AAPC) were estimated with 95% confidence intervals (CIs). Overall and 5-year relative survival analyses were conducted and supplemented with Cox regression to explore the effect of different characteristics on overall mortality. ResultsA total of 720 non-epithelial ovarian cancers were identified, corresponding to 3.4% of all ovarian malignancies. The majority of non-epithelial ovarian cancers were germ cell tumors (49.9%) and sex cord-stromal tumors (38.6%). The age-standardized incidence rate of germ cell tumors was stable over the study period, ranging between 0.33 and 0.39 per 100,000 woman-years. In contrast, the age-standardized incidence rate of sex cord-stromal tumors declined from 0.30 (1978–1987) to 0.09 (2008–2016) per 100,000 woman-years (AAPC = −5.15%; 95% CI: −7.29, −2.96). The 5-year relative survival of germ cell tumors and sex cord-stromal tumors was 94% and 79%, respectively, in the most recent period (2008–2011). Cox regression showed that overall mortality was associated with calendar year, age, and stage. ConclusionsThe incidence of germ cell tumors was stable over calendar time, whereas the incidence of sex cord-stromal tumors decreased significantly. Non-epithelial ovarian cancer overall mortality has decreased during the study period and this could not be explained by taking stage and age at diagnosis into account.

Hematopoietic Stem Cell Transplant Recipients Surviving at Least 2 Years from Transplant Have Survival Rates Approaching Population Levels in the Modern Era of Transplantation.

The health and outcomes of long-term survivors after hematopoietic cell transplant (HCT) are areas of evolving interest as short-term transplant outcomes improve. Because recent changes in transplant practice have likely changed the survivor population, we sought to assess the survival of a contemporary cohort of patients who were alive and free of disease 2 years after HCT. Data were extracted from first transplants documented between 2002 and 2011 in the Australasian Bone Marrow Transplant Recipient Registry on patients who received an allogeneic HCT for acute myeloid leukemia (AML), acute lymphoblastic leukemia, chronic myeloid leukemia (CML), non-Hodgkin lymphoma, and myelodysplastic syndromes or an autologous HCT for myeloma or lymphoma. Patients were included if they had survived at least 2 years without disease relapse or progression. Mortality rates were compared with standard Australian and New Zealand populations using relative-survival analysis. A total of 1562 allogeneic and 3822 autologous HCT patients were included, with a median follow-up of 5.6 years. Compared with a matched group of patients from our previous study from 1992 to 2001, the contemporary cohort of allogeneic HCT recipients was older and more likely to receive peripheral blood stem cells and from unrelated donors. Allogeneic HCT for AML increased, wheresa transplants for CML fell from 32% to 8%. Increasing use of reduced-intensity conditioning and unrelated donors was also seen. Long-term survival after allogeneic and autologous HCT were very similar to the previous 1992 to 2001 cohort despite changes in practice over time. Recipients of autologous HCT for myeloma demonstrated substantially lower overall survival than HCT for other indications with no clear plateau. Annual relative survival for survivors of allogeneic HCT was 96% to 99% of the general population but only 89% to 96% of the general population for recipients of autologous HCT. Late deaths were primarily due to nonrelapse causes after allogeneic HCT, but relapse or disease progression remained prominent for recipients of autologous HCT, particularly for myeloma. The management of late HCT effects is important to improve long-term survival of transplant recipients but should be tailored to the risks specific to the primary disease and transplant type. Future planning should account for the impact of the expected increase in transplant activity and number of survivors on resource utilization.

Abstract P3-08-68: Application of 21-gene recurrence score in patients with T1-2, N0-1 ER-positive/HER2 negative breast cancer: Survival analysis in relation to clinical risk score

Abstract Background: Incorporating 21-gene recurrence score (RS) into daily practice have saved chemotherapy in about more than two-third of ER(+)/HER2(-) patients. In those with node-positive disease, 21-gene RS showed a clinically meaningful benefit in terms of reducing chemotherapy. We investigated the rate of chemotherapy and a short-term clinical outcome in patients with T1-2, N0-1 ER(+)/HER2(-) breast cancer after we actively applied 21-gene RS in our daily practice. Method: We identified T1-2, N0-1, ER(+)/HER2(-) breast cancer patients who underwent breast surgery followed by adjuvant treatment from January 2014 to December 2018. The clinical risk score (CRS) was defined as low and high based on histologic grade, tumor size, and nodal status as used in MINDACT trial. The rate of chemotherapy and survival outcomes were analyzed according to CRS and whether 21-gene RS was performed or not. Also, the patients were classified into 3 groups: Group A, endocrine alone without 21-gene RS; Group B, endocrine or chemo-endocrine guided by 21-gene RS; Group C, chemo-endo without 21-gene RS. In the patients between 2014 and 2016, we investigated the recurrence-free survival (RFS). Results: In a total of 1,008 patients, there were 446 (44.2%) for group A, 352 (34.9%) for group B, and 210 (20.8%) for group C, showing that 21-gene RS was done in about one-third of all. The rate of high CRS was 18.2% (81 of 446) in the group A, 42.3% (149 of 352) in the group B, and 71.0% (149 of 210) in the group C (P&amp;lt;0.001). In the low-CRS group, 36 (17.7%) of 203 patients with 21-gene RS received chemotherapy and 61 (14.3%) of 365 patients without 21-gene RS received chemotherapy (P=0.268). However, in the high-CRS group, 46 (30.9%) of 149 patients with 21-gene RS received chemotherapy although 149 (64.8%) of 230 patients without 21-gene RS received chemotherapy (P&amp;lt;0.001). In the patients eligible for survival analyses, a median follow-up was 36 months. In women treated with endocrine alone, there were no difference of RFS between the patients with or without 21-gene RS (P=0.147). Also, the RFS did not differ between two groups with or without 21-gene RS, regardless of CRS (log-rank test, P=0.657 in the high-CRS group, and P=0.803 in the low-CRS group, respectively). Conclusions: These results supported that the application of 21-gene RS reduced the rate of chemotherapy in N0-1 patients with high CRS. Further study with a long-term follow up is needed to clarify an oncologic safety of a reduced the chemo-endocrine rate brought by 21-gene RS in terms of survival outcomes. Key words: breast neoplasm, adjuvant treatment, 21-gene recurrence score, chemotherapy Citation Format: Soong June Bae, Sung Gwe Ahn, Soeun Park, Chi Hwan Cha, Dooreh Kim, Janghee Lee, Joon Jeong. Application of 21-gene recurrence score in patients with T1-2, N0-1 ER-positive/HER2 negative breast cancer: Survival analysis in relation to clinical risk score [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-68.

Long-term outcomes after autologous stem cell transplantation for multiple myeloma

AbstractAs multiple myeloma (MM) treatments evolve, frequent updates are required to monitor the long-term effect of changes in approach. Traditionally, MM is considered an incurable disease, with most patients eventually relapsing. However, improvements in treatments has raised the possibility that MM might be functionally curable. To examine improvements in long-term survival, we followed 4329 patients with newly diagnosed MM treated with autologous stem cell transplantation (ASCT) at the University of Arkansas for Medical Sciences from 1989 through 2018. Overall survival (OS) and progression-free survival (PFS) were evaluated using Kaplan-Meier analysis, Cox proportional hazards models, relative survival analysis, and cure modeling among different time periods, risk groups, and demographic traits. Steady improvements in OS were found, with patients treated in 2014 or later having superior OS (hazard ratio, 0.35; 95% confidence interval [CI], 0.27-0.45) and reduced excess risk for MM death (relative excess risk, 0.30; 95% CI, 0.22-0.41) compared with patients treated in 1997 or earlier. Patients treated during intervening time periods often had intermediate survival, but trends in OS, PFS, and landmarked analyses were inconsistent. Cure models support the potential for cure, ranging from 6.3% to 31.3%, depending on the year of treatment, with 10.0% to 18.6% of patients achieving their normal life expectancy across multiple periods. There was some evidence of reductions in early mortality within 3 years of diagnosis, longer complete response (CR) duration, and reductions in relapse after achieving CR. However, results differed depending on age, risk group, and cytogenetic characteristics.

Sublobar resection compared with stereotactic body radiation therapy and ablation for early stage non–small cell lung cancer: A National Cancer Database study

ObjectivesTo compare the overall survival (OS) outcomes of sublobar resection (SLR) with stereotactic body radiation therapy (SBRT) or ablation for patients with early stage non–small cell lung cancer (NSCLC). MethodsPatients with clinical stage I (T1-T2aN0M0) NSCLC from 2004 to 2014 who were treated with SLR, SBRT, or ablation as the sole treatment were identified from the National Cancer Database. OS was estimated using the Kaplan–Meier method and evaluated by log-rank test, univariate and multivariate Cox proportional hazard regression, and propensity score–matched analysis. Relative survival analyses compared with age- and sex-matched US population were performed. ResultsA total of 53,973 patients were identified. The 1-, 2-, 3-, and 5-year relative survival rates were 96%, 90%, 84%, and 71% for SLR (n = 30,451); 93%, 78%, 65%, and 46% for SBRT (n = 22,134); and 90%, 73%, 58%, and 37% for ablation (n = 1388). Propensity score matching resulted in 9967 patients in the SBRT group versus 9967 in the SLR group and 1062 patients in the ablation group versus 1984 in the SLR group. After matching, both SBRT (hazard ratio, 1.559; 95% confidence interval, 1.497-1.623; P < .001) and ablation (hazard ratio, 1.906; 95% confidence interval, 1.730-2.101; P < .001) were associated with shorter OS when compared with SLR. These results persisted in patients with tumor size ≤2 cm. ConclusionsPreliminary results suggest SLR may be associated with longer OS in patients with early-stage NSCLC compared with SBRT or ablation. Future prospective, randomized, controlled clinical trials comparing these treatments are needed to confirm these results.

Survival After Elective Endovascular or Open AAA Repair: A Systematic Review and Meta-analysis

Introduction - Endovascular aneurysm repair (EVAR) has become the preferred strategy for elective AAA repair. However, superiority of EVAR has recently been challenged by reports of impaired longevity in patients who underwent elective endovascular repair. (1, 2) In this context we considered a systematic review and meta-analysis of the available survival data relevant. Possible confounding by age differences between patients receiving EVAR or open surgical repair (OSR) was addressed by estimating relative survival. Methods - A search using PubMed, Embase, Web of Science and Cochrane for the 1993-2018 interval identified 53 eligible papers that reported short-term and/or long-term mortality of EVAR and OSR. Identified studies included 4 randomized controlled trials (RCTs), 20 reports based on administrative registries, and 29 cohort studies. Pooled overall survival estimates (Hazard ratios with corresponding 95% CIs for EVAR versus OSR) were calculated using a random-effects model. For each study expected survival was calculated based on the matched (age, sex, year of operation and country) general population. Relative survival was consequently calculated as the ratio between observed and expected survival, according to EVAR or OSR. (3, 4) Results - The analysis includes data of 189.022 patients: 102.053 EVARs and 86.969 OSRs. Pooled 30-day mortality for EVAR was 1.16% (95% CIs 0.92 – 1.39) and 3.27% (95% CIs: 2.71 – 3.83) for OSR. Combined (overall) 3, 5, and 10-year survival rates were similar for EVAR and OSR. However, data from cohort studies indicated superior survival after OSR at 3 years and a trend towards superior survival at 5 and 10 years. Yet, EVAR patients included in these cohort studies were older (73.7 years) compared to OSR patients (71.4 years). Correction of age inequality through relative survival analysis showed comparable 3, 5, and 10 years survival for EVAR and OSR among all types of studies. Conclusion - Pooled data confirm superior 30-day survival of EVAR over OSR, but long-term survival up to 10 years is equivalent, when corrected for age inequality. Asymmetrical medical decision making with regard to EVAR and OSR may result in confounding by indication in the cohort and registry studies. Although relative survival estimates reduce the impact of age differences, it is plausible that fitter patients or patients with more complex AAA morphologies are more likely to receive OSR. Published data do not allow for extension beyond the 10-year survival window or for analysis of specific subgroups (women, young patients).