Risk of second primary malignancies associated with radiotherapy in prostate cancer patients: competing risk analysis

Background: The effect of radiotherapy (RT) for second primary malignancies (SPMs) among prostate cancer survivors is controversial. Methods: Applying logistic regression, competing risk analysis and propensity score matching method, this study analyzed clinical data from the Surveillance, Epidemiology, and End Results program to compare the risk for SPMs between patients receiving RT and non-RT. Results: In this study, prostate cancer patients treated with RT developed more SPMs in the anus, bladder, rectum, liver, lung and bronchus and lymphoma than non-RT groups. Conclusion: More intensive surveillance should be adopted for these cancers among prostate cancer survivors.

Decreasing Postoperative Pulmonary Complication Following Laparoscopic Surgery in Elderly Individuals with Colorectal Cancer: A Competing Risk Analysis in a Propensity Score–Weighted Cohort Study

Advanced age is a risk factor for major abdominal surgery due to a decline in physical function and increased comorbidities. Although laparoscopic surgery provides good results in most patients with colorectal cancer (CRC), its effect on elderly patients remains unclear. This study aimed to compare the short- and long-term outcomes between open and laparoscopic surgeries in elderly patients with CRC. Total 1350 patients aged ≥75 years who underwent curative resection for stage I–III primary CRC were enrolled retrospectively and were divided into open surgery (846 patients) and laparoscopy (504 patients) groups. After propensity score weighting to balance an uneven distribution, a competing risk analysis was used to analyze the short-term and long-term outcomes. Postoperative mortality rates were lower in the laparoscopy group, especially due to pulmonary complications. Postoperative hospital stay was significantly shorter in the laparoscopy group than in the open surgery group. Overall survival, disease-free survival, and competing risk analysis showed no significant differences between the two groups. Laparoscopic surgery for elderly patients with CRC significantly decreased pulmonary-related postoperative morbidity and mortality in this large cohort study. Laparoscopic surgery is a favorable method for elderly patients with CRC than open surgery in terms of less hospital stay and similar oncological outcomes.

Association of Prescription With Body Composition and Patient Outcomes in Incident Peritoneal Dialysis Patients

Objective: The nutritional status of patients on peritoneal dialysis (PD) is influenced by patient- and disease-related factors and lifestyle. This analysis evaluated the association of PD prescription with body composition and patient outcomes in the prospective incident Initiative for Patient Outcomes in Dialysis–Peritoneal Dialysis (IPOD-PD) patient cohort.Design and Methods: In this observational, international cohort study with longitudinal follow-up of 1,054 incident PD patients, the association of PD prescription with body composition was analyzed by using the linear mixed models, and the association of body composition with death and change to hemodialysis (HD) by means of a competing risk analysis combined with a spline analysis. Body composition was regularly assessed with the body composition monitor, a device applying bioimpedance spectroscopy.Results: Age, time on PD, and the use of hypertonic and polyglucose solutions were significantly associated with a decrease in lean tissue index (LTI) and an increase in fat tissue index (FTI) over time. Competing risk analysis revealed a U-shaped association of body mass index (BMI) with the subdistributional hazard ratio (HR) for risk of death. High LTI was associated with a lower subdistributional HR, whereas low LTI was associated with an increased subdistributional HR when compared with the median LTI as a reference. High FTI was associated with a higher subdistributional HR when compared with the median as a reference. Subdistributional HR for risk of change to HD was not associated with any of the body composition parameters. The use of polyglucose or hypertonic PD solutions was predictive of an increased probability of change to HD, and the use of biocompatible solutions was predictive of a decreased probability of change to HD.Conclusion: Body composition is associated with non-modifiable patient-specific and modifiable treatment-related factors. The association between lean tissue and fat tissue mass and death and change to HD in patients on PD suggests developing interventions and patient counseling to improve nutritional markers and, ultimately, patient outcomes.Study Registration: The study has been registered at Clinicaltrials.gov (NCT01285726).

A Nomogram for Predicting Brain Metastasis in IIIA-N2 Non-Small Cell Lung Cancer After Complete Resection: A Competing Risk Analysis

BackgroundBrain metastasis (BM) is one of the most common failure patterns of pIIIA-N2 non-small cell lung cancer (NSCLC) after complete resection. Prophylactic cranial irradiation (PCI) can improve intracranial control but not overall survival. Thus, it is particularly important to identify the risk factors that are associated with BM and subsequently provide instructions for selecting patients who will optimally benefit from PCI.Methods and MaterialsBetween 2011 and 2014, patients with pIIIA-N2 NSCLC who underwent complete resection in our institution were reviewed and enrolled in the study. Clinical characteristics, pathological parameters, treatment mode, BM time, and overall survival were analyzed. A nomogram was built based on the corresponding parameters by Fine and Gray’s competing risk analysis to predict the 1-, 3-, and 5-year probabilities of BM. Receiver operating characteristic curves and calibration curves were chosen for validation. A statistically significant difference was set as P <0.05.ResultsA total of 517 patients were enrolled in our retrospective study. The median follow-up time for surviving patients was 53.2 months (range, 0.50–123.17 months). The median age was 57 (range, 25–80) years. Of the 517 patients, 122 (23.6%) had squamous cell carcinoma, 391 (75.6%) received adjuvant chemotherapy, and 144 (27.3%) received post-operative radiotherapy. The 1-, 3-, and 5-year survival rates were 94.0, 72.9, and 66.0%, respectively. The 1-, 3-, and 5-year BM rates were 5.4, 15.7, and 22.2%, respectively. According to the univariate analysis, female, non-smokers, patients with non-squamous cell carcinoma, bronchial invasion, perineural invasion, and patients who received adjuvant chemotherapy were more likely to develop BM. In a multivariate analysis, non-squamous cell carcinoma (subdistribution hazard ratios, SHR: 3.968; 95% confidence interval, CI: 1.743–9.040; P = 0.0010), bronchial invasion (SHR: 2.039, 95% CI: 1.325–3.139; P = 0.0012), perineural invasion (SHR: 2.514, 95% CI: 1.058–5.976; P = 0.0370), and adjuvant chemotherapy (SHR: 2.821, 95% CI: 1.424–5.589; P = 0.0030) were independent risk factors for BM. A nomogram model was established based on the final multivariable analysis result. The area under the curve was 0.767 (95% CI, 0.758–0.777).ConclusionsFor patients with IIIA-N2 NSCLC after complete resection, a nomogram was established based on clinicopathological factors and treatment patterns for predicting the BM. Based on this nomogram, patients with a high risk of BM who may benefit from PCI can be screened.

Genomic Subgroups Impact Post-Transplant Survival in Patients with Myelodysplastic Syndrome: A CIBMTR Analysis

Background Myelodysplastic syndromes (MDS) are clonal stem cell malignancies characterized by cytopenia, inefficient hematopoiesis, dysplasia in one or more myeloid cell lineages and increased risk of development of acute myeloid leukemia. It has been well appreciated that genomic alterations play a key role in MDS pathogenesis. The Revised International Prognostic Scoring System (IPSS-R) algorithm is commonly used to predict overall survival but may fail to recapitulate reliable prognostic information at the individual patient level, especially at the time of hematopoietic cell transplantation (HCT). Current World Health Organization (WHO) classification includes MDS with isolated 5q deletion as the only genetically defined category. Comprehensive analysis of recurrent genomic features by unsupervised clustering empowers discovery of potential prognostic molecular signatures. Methods Using whole blood samples obtained from 494 MDS patients at the time of HCT, we conducted whole-genome sequencing (WGS) and somatic variant processing via a custom analytic pipeline based on OCTOPUS and a set of annotation databases. Multiple filters allowed for selection and fine-tuning of criteria, including removal of variants with Gnomad allele frequency above 10x10 -06, removal of noncoding variants in low complexity and repetitive regions, those with no functional indications from ANNOVAR annotations, CADD conservative score under 15, and absence in HGMD or COSMIC databases. Highly annotated clinical data, including cytogenetic abnormalities at the latest time point prior to HCT, were obtained from CIBMTR forms. K-means clustering was applied to recurrent mutations and cytogenetic abnormalities to identify clinically relevant genomic subtypes. The optimal cluster number was determined by Gap-status algorithm. Statistics of clinical characteristics were compared among different genomic subgroups by Chi-squared test for categorical variables and Mann-Whitney U test for continuous variables. Overall survival association tests were conducted by Cox multivariate models. Relapse and transplant-related risk were performed by competing risk analysis using Fine-Gray models. Models were adjusted for patient-, disease-, and HCT-related factors. Results The somatic genomic landscape in our MDS cohort was examined for the total count of recurrent mutations at the sample level and gene level. Among 53 recurrently mutated genes in 257 of 494 MDS cases, TP53, TET2, RUNX1, DNMT3A, and ASXL1 were the most frequently mutated genes in our MDS cohort. Based on k-means clustering of the recurrent mutational and cytogenetic data, we detected five clusters that stratified our MDS patient cohort, including one reference cluster with no recurrent somatic mutations or cytogenetic abnormalities. Compared to the reference subgroup, significantly higher cytogenetic scores and IPSS-R scores were observed in genomic clusters with TP53 mutations (cytogenetic score: P=3.42E-07*; IPSS-R score: P= 2.38E-10*) and cytogenetic abnormalities del5q, or tri8p (cytogenetic score: P= 2.38E-10*; IPSS-R score: P=0.09) , or mono7 (cytogenetic score: P=3.29E-13*; IPSS-R score: P=1.38E-05*) (data not shown). Cox multivariate models revealed that genomic clusters with TP53 and del5q mutations (P<0.001*) or tri8p (P=0.02*) mutations have strong associations with post-transplant overall survival outcome (Figure 1A). Furthermore, competing risk analysis confirmed significantly higher risk of relapse in genomic subgroups with TP53 and del5q mutations in the reduced intensity conditioning regimen setting (P=0.01) (Figure 1B), while significantly higher risk of transplant-related mortality was found in the genomic subgroup with tri8p in the myeloablative conditioning regimen setting (P=0.03) (Figure 1C). Conclusion Our study suggests that molecular signatures from MDS patient genomes at HCT may provide an independent prognosis of post-transplant survival. Additionally, our data suggests that the choice of regimen intensity could be informed by knowledge of the individual genomic signature of a given MDS patient. Figure 1 Figure 1. Disclosures Saber: Govt. COI: Other.