Multivariable Competing Risk Regression Models Research Articles

The role of chemotherapy in patients with T1bN0M0 triple-negative breast cancer: a real-world competing risk analysis.

The objective of the present study was to implement Kaplan-Meier analysis, competing risk analysis, and propensity score matching to evaluate whether the patients with T1bN0M0 triple-negative breast (TNBC) could benefit from adjuvant chemotherapy. A total of 1849 patients were identified in the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. All eligible patients were divided into two cohorts, the chemotherapy (1155 patients) and the no-chemotherapy (694 patients) cohorts. Similar 5-year breast cancer-specific survival (BCSS) was observed in the chemotherapy and no-chemotherapy cohorts (96.1% vs. 96.0%, p=0.820). The results of the competing risk analysis showed a comparable 5-year breast cancer-specific death (BCSD) in both groups (chemotherapy 3.6% vs. no-chemotherapy 3.4%, p=0.778). Also, a higher 5-year other causes death (OCD) was observed in the no-chemotherapy cohort (0.7% vs. 5.4%, p<0.001). Multivariable competing risks regression models showed no association between chemotherapy and BCSS (HR, 1.21; 95%CI, 0.64-2.31; p=0.560). After 1:1 PSM, no significant difference was also observed for BCSD and OCD between two cohorts. The value of adjuvant chemotherapy in patients with T1bN0M0 TNBC is less than the present guidelines recommend, suggesting that de-escalated treatment could be a potentially beneficial strategy in appropriately selected patients.

The effect of race/ethnicity on histological subtype distribution, stage at presentation and cancer specific survival in urethral cancer

ObjectiveTo test the effect of race/ethnicity on histological subtype, stage at presentation, and cancer specific mortality (CSM) in urethral cancer patients. Material and MethodsStratified analyses (Surveillance, Epidemiology and End Results [2004–2016]) tested the effect of race/ethnicity on histology and stage. Cumulative incidence-plots and multivariable competing-risks regression models (CRR), addressed CSM, after matching for TNM-stage, histology, age, and gender. ResultsOf 1,904 urethral cancer patients, 71% were Caucasian, 16% African American, 7% Hispanic and 5% other. African Americans were younger (66 years) than Caucasians (73 years) and Hispanics (74 years). In African Americans, adenocarcinoma (25%) and squamous cell carcinoma (SCC; 29%) were more frequent than in Caucasians (12% and 23%) or Hispanics (15% and 20%). African Americans with adenocarcinoma exhibited higher stage than other adenocarcinoma patients. In CRR, African Americans (35%) and Hispanics (29%) exhibited highest and second highest 3-year CSM, even after matching. After further multivariable adjustment of matched CRRs, CSM was higher in Hispanics (HR: 1.93, P= 0.03) and in African Americans (Hazard ratio 1.35, P= 0.07), relative to Caucasians. ConclusionRace/ethnicity impacts important differences on urethral cancer patients. African American race/ethnicity predisposes to higher rate of SCC and adenocarcinoma. Moreover, African Americans are younger and present with higher stage at diagnoses. Finally, even after most detailed matching for stage, age, gender, and adjustment for treatment and systemic therapy and socioeconomic status, African Americans and Hispanics exhibit higher CSM than Caucasians.

Orthopedic Toxicity Among Adolescents and Young Adults Treated on DFCI ALL Consortium Trials

Orthopedic Toxicity Among Adolescents and Young Adults Treated on DFCI ALL Consortium Trials

Differences between rural and urban prostate cancer patients

BackgroundWe hypothesized that the residency status (rural area [RA] vs urban clusters [UC] vs urban areas [UA]) affects stage and cancer-specific mortality (CSM) in contemporary newly diagnosed prostate cancer (PCa) patients of all stages, regardless of treatment.MethodsNewly diagnosed PCa patients with available residency status were abstracted from the Surveillance, Epidemiology, and End Results database (2004–2016). Propensity-score (PS) matching, cumulative incidence plots, multivariate competing-risks regression (CRR) models were used.ResultsOf 531,468 PCa patients of all stages, 6653 (1.3%) resided in RA, 50,932 (9.6%) in UC and 473,883 (89.2%) in UA. No statistically significant or clinically meaningful differences in stage at presentation or CSM were recorded. Conversely, 10-year other cause-mortality (OCM) rates were 27.2% vs 23.7% vs 18.9% (p < 0.001) in RA vs UC vs UA patients, respectively. In CRR models, RA (subhazard ratio [SHR] 1.38; p < 0.001) and UC (SHR 1.18; p < 0.001) were independent predictors for higher OCM relative to UA. These differences remained statistically significant in fully PS-adjusted multivariate CRR models.ConclusionRA, and to a lesser extent UC, PCa patients are at higher risk of OCM than UA patients. Higher OCM may indicate shorter life expectancy and should be considered in treatment decision making.

Effect of Age on Cancer-specific Mortality in Patients With Urothelial Carcinoma of the Urinary Bladder: A Population-based Competing-risks Analysis Across Disease Stages.

The objective of the study is to test the effect of age on cancer-specific mortality (CSM) in patients with urothelial carcinoma of the urinary bladder (UCUB), across all disease stages. Within the Surveillance, Epidemiology, and End Results (SEER) registry (2004-2016), we identified 207,714 patients. Age was categorized as: below 60 versus 60 to 69 versus 70 to 79 versus 80 years and above. Multivariable competing-risks regression (CRR) models were used according to disease stage (low-risk nonmuscle invasive: TaN0M0 low grade, high-risk nonmuscle invasive: Ta high grade or Tis-1N0M0, muscle invasive: T2-3N0M0, regional: T4N0M0/TanyN1-3M0, and metastatic: TanyNanyM1). Overall, 33,970 (16.4%) versus 52,173 (25.1%) versus 64,537 (31.1%) versus 57,034 (27.4%) patients were below 60 versus 60 to 69 versus 70 to 79 versus 80 years and above, respectively. In multivariable CRR models that focused on low-risk nonmuscle invasive UCUB, advanced age was associated with higher CSM rates (hazard ratio [HR]: 7.04 in patients aged 80 y and above, relative to below 60 y; P<0.001). Moreover, advanced age was also associated with higher CSM rates in high-risk nonmuscle invasive UCUB (HR: 2.77 in patients aged 80 y and above, relative to below 60 y; P<0.001) and in muscle invasive UCUB patients (HR: 1.38 in patients aged 80 y and above, relative to below 60 y; P<0.001). Conversely, lower CSM rates with advanced age were observed in multivariable CRR that focused on regional (HR: 0.91 for patients aged 80 y and above, relative to below 60 y; P=0.02) or metastatic UCUB (HR: 0.75 for patients aged 80 y and above, relative to below 60 y; P<0.001). The direction and the magnitude of the association between advanced age and CSM in UCUB patients changes according to tumor stage. In low-risk nonmuscle invasive, high-risk nonmuscle invasive, and muscle invasive UCUB, more advanced age is associated with higher CSM rates. Conversely, in regional and metastatic UCUB patients, more advanced age is associated with lower CSM rates.

Lung transplant waitlist outcomes in the United States and patient travel distance.

There is a broad range of patient travel distances to reach a lung transplant hospital in the United States. Whether patient travel distance is associated with waitlist outcomes is unknown. We present a cohort study of patients listed between January 1, 2006 and May 31, 2017 using the Scientific Registry of Transplant Recipients. Travel distance was measured from the patient's permanent zip code to the transplant hospital using shared access signature URL access to Google Maps, and assessed using multivariable competing risk regression models. There were 22 958 patients who met inclusion criteria. Median travel distance was 69.7 miles. Among patients who traveled>60 miles, 41.2% bypassed a closer hospital and sought listing at a more distant hospital. In the adjusted models, when compared to patients who traveled ≤60 miles, patients who traveled >360 miles had a 27% lower subhazard ratio (SHR) for waitlist removal (SHR 0.73, 95% confidence interval [CI]: 0.60, 0.89, P=.002), 16% lower subhazard for waitlist death (SHR 0.84; 95% CI 0.73-0.95, P=.07), and 13% increased likelihood for transplant (SHR 1.13, 95% CI: 1.07, 1.20, P<.001). Many patients bypassed the nearest transplant hospital, and longer patient travel distance was associated with favorable waitlist outcomes.

Effect of Capacity to Undertake Instrumental Activities of Daily Living on Entry to Aged Residential Care in Older People With Heart Failure.

Background: Heart failure is a common condition in older people with complex medical needs. A key factor in resilience after heart failure is the capacity to perform the instrumental activities of daily living (IADLs). Knowing the association between capacity to perform IADLs and entry into aged residential care will help health professionals plan interventions that will allow older people to remain independent longer.Methods: We analyzed the association between the capacity to perform eight IADLs and entry into ARC. Participants included New Zealanders aged ≥65 years with a diagnosis of heart failure, and who had an InterRAI 9.1 Home Care assessment between July 2012 and June 2018. A multivariable competing risks regression model for entry to ARC with death as the competing risks was used to establish sub-hazard ratios (SHR) for IADL capacity. Co-variates included demographic variables, co-morbidities, living arrangements, cognitive performance, depression, timed walk, alcohol use, smoking, activities of daily living, recent hospitalization and history of falls.Results: There were 13,220 participants with heart failure who were followed for a median 1.69 (0.70–3.17) years. There were 3,177 (24.0%) participants who entered aged residential care and 5,714 (43.2%) who died without having first entered residential care. Overall capacity to perform specific IADLs was “very poor” for housework (85.5%), shopping (68.0%), stairs (61.7%), meal preparation (53.0%), and transportation (52.2%). In the multivariable model, compared to adequate capacity (the reference) poorer capacity for managing finance, managing medications, meal preparation and transport were all associated with increased risk of entering aged residential care, with SHR from 1.05 to 1.18. Overall, the IADL capacity explained ~10% of the risk of entering aged residential care.Conclusion: Capacity to perform IADL is a key factor in maintaining resilience in older people with heart failure. Capacity to manage finances, transport and medications, prepare meals, and transport oneself with minimal supervision could reduce the risk of entry into aged residential care. Developing early interventions and support for people with poor capacity to perform their IADL may help reduce admission into aged residential care.

Cause-specific mortality of type B aortic dissection and assessment of competing risks of mortality

ObjectiveNatural history studies of type B aortic dissection (TBAD) commonly report all-cause mortality. Our aim was to determine cause-specific mortality in TBAD and to evaluate the clinical characteristics associated with aorta-related and nonaorta-related mortality. MethodsClinical and administrative records were reviewed for patients with acute TBAD between 1995 and 2017. Demographics, comorbidities, presentation, and initial imaging findings were abstracted. Cause of death was ascertained through a multimodality approach using electronic health records, obituaries, social media, Social Security Death Index, and state mortality records. Causes of death were classified as aorta related, nonaorta related, or unknown. A Fine-Gray multivariate competing risk regression model for subdistribution hazard ratio was employed to analyze the association of clinical characteristics with aorta-related and nonaorta-related mortality. ResultsA total of 275 individuals met inclusion criteria (61.1 ± 13.7 years, 70.9% male, 68% white). Mean survival after discharge was 6.3 ± 4.7 years. Completeness of follow-up Clark C index was 0.87. All-cause mortality was 50.2% (n = 138; mean age, 70.1 ± 14.6 years) including an in-hospital mortality of 8.4%. Cause-specific mortality was aorta related, nonaorta related, and unknown in 51%, 43%, and 6%, respectively. Compared with patients with nonaorta-related mortality, patients with aorta-related mortality were younger at acute TBAD (69.5 ± 11.2 years vs 61.6 ± 15.5 years; P = .001), underwent more descending thoracic aortic repairs (19.4% vs 45.8%; P = .002), and had a shorter survival duration (5.7 ± 3.9 vs 3.4 ± 4.5 years; P = .002). There was clear variation in cause of death by each decade of life, with higher aorta-related mortality among those younger than 50 years and older than 70 years and a stepwise increase in nonaorta-related mortality with each increasing decade (P < .001). All-cause mortality at 1 year, 3 years, and 10 years was 15%, 24%, and 57%, respectively. After accounting for competing risks, the cumulative incidence of aorta-related mortality at 1 year, 3 years, and 10 years was 8.9%, 16.5%, and 27.2%, respectively, and that of nonaorta-related mortality was 2.7%, 7.2%, and 29%, respectively. A maximum descending thoracic aortic diameter >4 cm was associated with an increase in hazard of aorta-related mortality by 84% (subdistribution hazard ratio, 1.84; 95% confidence interval, 1.03-3.28) on multivariate competing risk regression analysis. ConclusionsTBAD is associated with high 10-year mortality. Those at risk for aorta-related mortality have a clinical phenotype different from that of individuals at risk for nonaorta-related mortality. This information is important for building risk prediction models that account for competing mortality risks and to direct optimal and individualized surgical and medical management of TBAD.

Effect of stage and grade migration on cancer specific mortality in renal cell carcinoma patients, according to clear cell vs. non-clear cell histology: A contemporary population-based analysis

ObjectivesTo test the effect of stage and grade migration on cancer specific mortality (CSM) in renal cell carcinoma (RCC) patients, according to clear cell (ccRCC) vs. non-ccRCC histology. Methods and MaterialsWithin the Surveillance, Epidemiology, and End Results registry (2004–2015), we identified patients with ccRCC and non-ccRCC (papillary [papRCC], chromophobe [chRCC], sarcomatoid [sarcRCC], and collecting duct [cdRCC]). Two consecutive time groups were considered – historical (2004–2009) and contemporary era (2010–2015). Temporal trends of tumor characteristics were evaluated. Cumulative incidence plots and multivariable competing risks regression models tested the effect of year groups on CSM. ResultsOverall, 24,746 and 73,228 patients with non-ccRCC and ccRCC were evaluated. Of those, 42% and 58% were recorded in historical and contemporary era. Time trend analyses showed (1) tumor size decreased for non-ccRCC (estimated annual percent changes [EAPC]: −1.1%; P <0.01) and for ccRCC (EAPC: −1.0%; P <0.01), (2) rates of G3/G4 decreased for non-ccRCC (EAPC: −0.7%; P = 0.03), but increased for ccRCC (EAPC: +1.1; P <0.01), 3) rates of node positive disease decreased for non-ccRCC (EAPC:−3.1%; P = 0.02), but were stable for ccRCC (EAPC: +0.4; P =0.5), (4) rates of metastatic disease at diagnosis decreased for non-ccRCC (EAPC: −3.2%; P <0.01), but were stable for ccRCC (EAPC: −0.6%; P = 0.1), (5) among non-ccRCC, the percentage of papRCC increased (EAPC:+1%; P <0.01), while the percentage of sarcRCC (EAPC: −7%; P <0.01) and cdRCC (EAPC: −11.2%; P <0.01) decreased. Finally, in multivariable CRR models, lower CSM was recorded for contemporary non-ccRCC (HR: 0.7; P <0.001) and ccRCC (HR: 0.8; P <0.001) patients. ConclusionOur findings illustrate a favorable stage and grade migration and improved cancer-specific mortality in contemporary non-ccRCC. Additionally, despite absence of meaningful stage migration in ccRCC, improved cancer-specific mortality in contemporary patients was also recorded. In consequence, a 2-tiered process appears to be operational in non-ccRCC vs. a 1-tiered phenomenon in ccRCC.

Incidence and predictors of loss to follow up among adult HIV patients on antiretroviral therapy in University of Gondar Comprehensive Specialized Hospital: A competing risk regression modeling.

Loss to follow up after the initiation of antiretroviral therapy (ART) is common in Africa, particularly in Ethiopia and it is a considerable obstacle for the effectiveness of the ART program. Mortality is a competing risk of loss to follow up but it is often overlooked and there is limited evidence about the incidence and predictors of loss to follow up in the presence of competing events. To assess the Incidence and predictors of loss to follow up among adult HIV patients on ART in University of Gondar Comprehensive Specialized Hospital between January 1, 2015, and December 31, 2018. Institution based retrospective follow up study was conducted in University of Gondar Comprehensive Specialized Hospital. A Gray's test and cumulative incidence curve were used to compare the cumulative incidence function of loss to follow up. Bivariable and multivariable competing risk regression models were fitted to identify the predictors of lost to follow up and those variables with p-value <0.05 in the multivariable analysis was considered as significant predictors of lost to follow up. A total of 531 adult HIV patients on ART were included in the analysis. The incidence rate of loss to follow up in this study was 10.90 (95% CI: 8.9-13.2) per 100 person years. Being age group 15-30 years (aSHR = 2.01; 95%CI;1.11-3.63), being daily laborer(aSHR = 2.60; 95%CI;1.45-4.66), not receiving cotrimoxazole preventive therapy (aSHR = 2.66; 95%CI;1.68-4.21), not receiving isoniazid preventive therapy(aSHR = 4.57; 95% CI;1.60-13.08), ambulatory functional status (aSHR = 1.61; 95% CI; 1.02-2.51) and taking AZT-3TC-NVP medication at start of ART(aSHR = 2.01; 95% CI; 1.16-3.78) were significant predictors of lost to follow up. In this study the incidence of lost to follow up was high. Young people, daily laborer, ambulatory patients and those taking AZT-3TC-NVP as well as those who did not take opportunistic prophylaxis were at higher risk of loss to follow up. Therefore, giving special attention to the high-risk groups for lost to follow up highlighted in this study could decrease the rate of LTFU.

Cumulative Incidence of Subsequent Malignancy after Allo-HCT with Myeloablative Chemotherapy Plus Low-Dose Total Body Irradiation Versus Myeloablative Chemotherapy Alone.

<h3>Introduction</h3> Total body irradiation (TBI) has been described as a major risk factor for the development of subsequent malignancies (SMs) after allogeneic hematopoietic cell transplant (allo-HCT). However, a recent study found that lower doses (< 450cGy) of TBI used with non-myeloablative conditioning conferred no more risk than that attributed to treatment with myeloablative chemotherapy alone. It is not clear whether addition of low dose TBI to myeloablative chemotherapy protocols increases risk of SM. At our centre, in approximately 2004, 400 cGy TBI was added to our standard myeloablative fludarabine/busulfan regimen. We hypothesized that no significant difference in the cumulative incidence of SMs would be observed between the cohort of patients who received myeloablative chemotherapy (no TBI group) versus those who received the same plus 400cGy of TBI in 2 fractions (TBI group). <h3>Methods</h3> We identified 676 sequentially treated 1-year survivors who received a first allo-HCT between 1999 and 2014 from a provincial database. All patients but one (aplastic anemia) received HCT for hematological malignancies. The cumulative incidence of SMs in the TBI group (N=424) & no TBI group (N=252) were compared using a multivariate competing risk regression model. Death without SM was treated as a competing risk. Covariates included age at HCT, sex, moderate-severe cGVHD & stem cell source. Squamous and basal cell carcinomas of the skin, post-transplant lymphoproliferative disease, and relapse of primary malignancy were excluded. <h3>Results</h3> Median age at HCT was 47 (IQR 36-56). A total of 47 patients developed 54 SMs at a median of 5.7 years post HCT (IQR 1.2-12.9 years). At a median follow-up for surviving patients of 8.1 years (range 1.1-19.8 years), the cumulative incidence of SM was 7.0% (95% CI: 5.3-9.1%). Sites of malignancy were: gastrointestinal (N=11), genitourinary/gynecologic (N=10), lung (N=9), skin (N=7), prostate (N=5), breast (N=4), thyroid (N=3), oropharyngeal (N=3) and hematologic (N=2). TBI was not associated with increased risk of SMs when compared to the chemotherapy-alone regimen (figure 1, sHR 0.68, 95% CI 0.39-1.19, p=0.18), while older age at HCT (sHR 1.07, 95% CI 1.04-1.1, p<0.001) and a history of moderate-severe cGVHD (sHR 1.76, 95% CI 0.99-3.14, p=0.056) were. <h3>Conclusion</h3> Low dose TBI added to myeloablative chemotherapy does not appear to be associated with an increased risk of SMs when compared to myeloablative chemotherapy alone. These data may inform patient counselling and cancer screening practices for allo-HCT recipients that have been treated with myeloablative chemotherapy plus low dose TBI protocols.

Survival of Contemporary Patients With Non-metastatic Small-cell Carcinoma of Urinary Bladder, According to Alternative Treatment Modalities.

The objective of this study was to test the effect of chemotherapy and/or radical cystectomy (RC) and/or radiotherapy (RT) on survival of patients with non-metastatic small-cell carcinoma of the urinary bladder (SCCUB). Within the Surveillance, Epidemiology, and End Results registry (2001-2016), we identified patients with non-metastatic (T1-4, N0, M0) SCCUB. Treatment was defined as: chemotherapy alone, chemotherapy+ RC, and chemotherapy+ RT. Temporal trends, cumulative incidence plots, and multivariable competing risks regression models were used. Of 595 patients with SCCUB, 230 (38.5%), 159 (27%), and 206 (34.5%) were treated with chemotherapy alone, chemotherapy+ RC, and chemotherapy+ RT, respectively. The rates of chemotherapy+ RC increased (estimated annual percentage changes [EAPC],+5.9%; P= .002). Conversely, chemotherapy alone (EAPC,-1.7%; P= .1) and chemotherapy+ RT rates decreased (EAPC:-2.2%; P= .08). Overall, 5-year cancer-specific mortality (CSM) rates were 44%, 29%, and 40% for patients treated with chemotherapy alone, chemotherapy+ RC, and chemotherapy+ RT, respectively (P= .004). Relative to chemotherapy alone, patients treated with chemotherapy+ RC experienced lower CSM (hazard ratio, 0.5; P< .001). Conversely, patients treated with chemotherapy+ RT did not exhibit any CSM benefit (hazard ratio, 0.8; P= .2), when compared with chemotherapy alone. In contemporary patients with SCCUB with non-metastatic disease, the rates of chemotherapy+ RC are increasing. Conversely, the rates of combined chemotherapy with RT and chemotherapy alone are decreasing. These patterns of treatment are in agreement with better cancer control in patients with SCCUB. In consequence, until more robust data become available, the combination of chemotherapy and RC should represent the recommended treatment strategy.

Primary lymphomas of the genitourinary tract: A population-based study

ObjectiveWe performed a population-based analysis focusing on primary extranodal lymphoma of either testis, kidney, bladder or prostate (PGUL). MethodsWe identified all cases of localized testis, renal, bladder and prostate primary lymphomas (PL) versus primary testis, kidney, bladder and prostate cancers within the Surveillance, Epidemiology, and End Results database (1998–2015). Estimated annual proportion change methodology (EAPC), multivariable logistic regression models, cumulative incidence plots and multivariable competing risks regression models were used. ResultsThe rates of testis-PL, renal-PL, bladder-PL and prostate-PL were 3.04%, 0.22%, 0.18% and 0.01%, respectively. Patients with PGUL were older and more frequently Caucasian. Annual rates significantly decreased for renal-PL (EAPC: −5.6%; p=0.004) and prostate-PL (EAPC: −3.6%; p=0.03). In multivariable logistic regression models, older ager independently predicted testis-PL (odds ratio [OR]: 16.4; p<0.001) and renal-PL (OR: 3.5; p<0.001), while female gender independently predicted bladder-PL (OR: 5.5; p<0.001). In surgically treated patients, cumulative incidence plots showed significantly higher 10-year cancer-specific mortality (CSM) rates for testis-PL, renal-PL and prostate-PL versus their primary genitourinary tumors. In multivariable competing risks regression models, only testis-PL (hazard ratio [HR]: 16.7; p<0.001) and renal-PL (HR: 2.52; p<0.001) independently predicted higher CSM rates. ConclusionPGUL rates are extremely low and on the decrease in kidney and prostate but stable in testis and bladder. Relative to primary genitourinary tumors, PGUL are associated with worse CSM for testis-PL and renal-PL but not for bladder-PL and prostate-PL, even after adjustment for other-cause mortality.

Incidence and Risk Factors of Second Malignancies Among Medicare Beneficiaries with Newly-Diagnosed Philadelphia Chromosome-Negative Classical Myeloproliferative Neoplasms Receiving Cytoreductive Therapy with Hydroxyurea

Incidence and Risk Factors of Second Malignancies Among Medicare Beneficiaries with Newly-Diagnosed Philadelphia Chromosome-Negative Classical Myeloproliferative Neoplasms Receiving Cytoreductive Therapy with Hydroxyurea

Surgical resection margin classifications for high-grade pleomorphic soft tissue sarcomas of the extremity or trunk: definitions of adequate resection margins and recommendations for sampling margins from primary resection specimens

Adequacy of surgical resection margins for soft tissue sarcomas are poorly defined because of the various classifications and definitions used in prior studies of heterogeneous patient cohorts and inconsistent margin sampling protocols. Surgical resection margins of 166 primary, high-grade, pleomorphic sarcomas of the extremity or trunk were classified according to American Joint Committee on Cancer R and Musculoskeletal Tumor Society categories, as well as by metric distance and tissue composition. None of the cases were treated with neoadjuvant therapy. Multivariable competing risk regression models were evaluated and optimal surgical resection margins for each classification system were defined. Minimum safe tumor clearance was 5 mm without use of adjuvant radiotherapy and 1 mm with adjuvant radiotherapy. Predictive accuracy of margin classification systems was compared by area under receiver-operating characteristic curves generated from logistic regression of 2½-year local recurrence-free survival and other standard tests of diagnostic accuracy. The Musculoskeletal Tumor Society and margin distance classifications performed similarly, both of which showed higher sensitivity and negative predictive value compared to the American Joint Committee on Cancer R classification. The prognostic power of close or positive margins in prediction models significantly increased when six or more slides were submitted for assessment of surgical resection margins. Surgical resection margins for soft tissue sarcoma should be reported using the Musculoskeletal Tumor Society classification or metric distance to the closest resection margin. Musculoskeletal Tumor Society wide/radical margins or tumor clearances of 5 mm (without adjuvant radiotherapy) or 1 mm (with adjuvant radiotherapy) appear to define the minimum safe surgical resection margins necessary to decrease the likelihood of local recurrence of high-grade pleomorphic sarcomas of the extremity or trunk.

Effectiveness of Intravesical Doxorubicin Immediately Following Resection of Primary Non-muscle-invasive Bladder Cancer: A Propensity Score-matched Analysis.

The purpose of this study was to investigate whether adding single immediate postoperative intravesical instillation of doxorubicin (SID) to transurethral resection of bladder tumor (TURBT) significantly reduced the risk of recurrence in patients with non-muscle-invasive bladder cancer (NMIBC). We retrospectively analyzed the records of 720 patients diagnosed with primary NMIBC between 2002 through 2018 at the Kameda Medical Center. The primary outcome measure was time to recurrence. Time to progression was also compared. The cohort of SID and the cohort of TURBT alone were matched one-to-one by propensity scores. Matching was done by patient age, gender, and factors of the European Organization of Research and Treatment of Cancer recurrence risk table. The associations of adding SID and clinical outcomes were assessed with uni- and multivariate competing-risk regression models. After matching, a total of 364 patients, including 182 receiving SID and 182 receiving TURBT alone, were analyzed. No statistically significant differences existed among the measured baseline characteristics in propensity score-matched cohorts. In the multivariate analysis, there was a significantly longer time to recurrence in patients receiving SID (subdistribution hazard ratio, 0.68; 95% confidence interval, 0.49-0.95; P= .024) in propensity score-matched cohorts. There was no significant difference in time to progression (subdistribution hazard ratio, 0.61; 95% confidence interval, 0.11-3.49; P= .58) in univariate analysis. Our results demonstrated that SID significantly reduced the recurrence risk of primary NMIBC. Doxorubicin could be an inexpensive alternative to other evidenced-based chemotherapeutic agents for single immediate intravesical chemotherapy.

Assessment of local tumor ablation and non-interventional management versus partial nephrectomy in T1a renal cell carcinoma.

Local tumor ablation (LTA) and non-interventional management (NIM) emerged as alternative management options for T1a renal cell carcinoma (RCC). We investigated trends and cancer-specific mortality (CSM) after LTA and NIM, compared to partial nephrectomy (PN). Within the Surveillance, Epidemiology, and End Results database (2004-2015), T1a RCC patients treated with PN, LTA or NIM were identified. Estimated annual proportion change methodology (EAPC), 1:1 ratio propensity score (PS) matching, cumulative incidence plots and multivariable competing risks regression models (CRR) were used to compare LTA vs. PN and NIM vs. PN. Subgroup analyses focused on patients <65 and ≥65 years. Overall 4524 patients underwent LTA vs. 1654 NIM vs. 25,435 PN. Annuals rates increased for NIM (EAPC: +3.3%, P<0.001), but not for either LTA or PN. After PS-matching in multivariable CCR, LTA (HR 1.9, P<0.001) and NIM (HR 3.0, P<0.001) showed worse 5-year CSM, relative to PN. In subgroup analyses, LTA showed no CSM disadvantage relative to PN in younger patients (HR 2.0, P=0.07). In older patients 1.64-fold CSM increase was recorded. Conversely, NIM younger (HR 3.1, P=0.001) and older (HR 3.1, P<0.001) patients exhibited higher CSM relative to PN. In T1a RCC patients, NIM rates showed a modest but significant increase, while LTA and PN rates remained stable. In survival analyses, LTA exhibited higher CSM rates only for elderly patients. Conversely, NIM exhibited higher CSM rates in both younger and older patients.

Impacts of Interleukin-18 Polymorphisms on the Incidence of Delayed-Onset Cytomegalovirus Infection in a Cohort of Kidney Transplant Recipients.

BackgroundThe incidence of cytomegalovirus (CMV) infection in solid organ transplant recipients may be reduced by antiviral prophylaxis, but this strategy may lead to delayed-onset CMV infection. The proinflammatory cytokine interleukin (IL)-18 plays a major role in viral host defense responses. This study examines the impacts of 2 single-nucleotide polymorphisms (SNPs) in the promoter region of the IL-18 gene, -607C/A (rs1946518) and -137G/C (rs187238), on the incidence of delayed-onset CMV infection in patients undergoing kidney transplant.MethodsThis retrospective study analyzed 2 IL-18 SNPs in consecutive adult kidney transplant recipients using real-time polymerase chain reaction with TaqMan probes. Participants were enrolled over the period 2005–2013 and stratified according to their IL-18 SNP genotype. The concordance index (Harrell’s c-index) was used as a measure of the discriminatory power of the predictive models constructed with bootstrapping to correct for optimistic bias.ResultsSeven hundred nine patients received transplants in the study period, and 498 met selection criteria. Cytomegalovirus infection and disease incidence were 38% and 7.5%, respectively. In multivariate competing risk regression models, carriers of the -607C/-137G haplotype who received prophylaxis showed a higher incidence of CMV replication after antiviral agent discontinuation (hazard ratio = 2.42 [95% confidence interval, 1.11–5.26]; P = .026), whereas CMV disease was not observed in those given prophylaxis who were noncarriers of this polymorphism (P = .009).ConclusionsOur findings suggest that the -607C/-137G IL-18 haplotype is associated with a higher incidence of postprophylaxis CMV replication. The prior identification of this polymorphism could help select alternative measures to prevent delayed-onset CMV infection in these patients.

Long-term incidence of secondary bladder and rectal cancer in patients treated with brachytherapy for localized prostate cancer: a large-scale population-based analysis.

To examine the incidence and time trends of secondary bladder cancer (BCa) and rectal cancer (RCa) after brachytherapy (BT) relative to radical prostatectomy (RP). Within the Surveillance, Epidemiology and End Results (SEER) database (1988-2015), we identified patients with localized PCa as an only or first primary cancer, who underwent BT or RP. Cumulative incidence plots and multivariable competing-risks regression (CRR) models were used. Sensitivity analyses focused on patients' age and year of diagnosis intervals and tested the effect of an unmeasured confounder. Of 318058 patients with localized prostate cancer (PCa), 55566 (18.4%) underwent BT. After propensity score-matching, 20-year secondary BCa incidence was 6.0% in patients who had undergone BT vs 2.4% in those who had undergone RP (P < 0.001) and the respective 20-year secondary RCa incidence was 1.1% vs 0.5% (P < 0.001). In multivariable CRR models, BT predicted higher secondary BCa (hazard ratio [HR] 1.58; P < 0.001) and RCa rates (HR 1.59; P < 0.001) vs RP. Sensitivity analyses replicated the same results after stratification according to age and showed HRs of decreasing magnitude for historical, intermediate and contemporary years of diagnosis. An unmeasured confounder with an HR of 2 would render the effect of BT statistically insignificant if it affected patients in the RP group with a ratio of 2 relative to those in the BT group. Finally, temporal trends showed a decrease of secondary 5-year BCa and RCa rates.> CONCLUSIONS: Brachytherapy predominantly increases the risk of secondary BCa and, to a lesser extent, that of RCa. Follow-up of such patients is therefore required. It is encouraging that both secondary BCa, and RCa rates, in particular, have recently decreased, RCa.

Ethnic differences in prediabetes incidence among immigrants to Canada: a population-based cohort study

BackgroundPrediabetes appears to be increasing worldwide. This study examined the incidence of prediabetes among immigrants to Canada of different ethnic origins and the age at which ethnic differences emerged.MethodsWe assembled a cohort of Ontario adults (≥ 20 years) with normoglycemia based on glucose testing performed between 2002 and 2011 through a single commercial laboratory database (N = 1,772,180). Immigration data were used to assign ethnicity based on country of origin, mother tongue, and surname. Individuals were followed until December 2013 for the development of prediabetes, defined using either the World Health Organization/Diabetes Canada (WHO/DC) or American Diabetes Association (ADA) thresholds. Multivariate competing risk regression models were derived to examine the effect of ethnicity and immigration status on prediabetes incidence.ResultsAfter a median follow-up of 8.0 years, 337,608 individuals developed prediabetes. Using definitions based on WHO/DC, the adjusted cumulative incidence of prediabetes was 40% (HR 1.40, CI 1.38–1.41) higher for immigrants relative to long-term Canadian residents (21.2% vs 16.0%, p < 0.001) and nearly twofold higher among South Asian than Western European immigrants (23.6%; HR 1.95, CI1.87–2.03 vs 13.1%; referent). Cumulative incidence rates based on ADA thresholds were considerably higher (47.1% and 32.3% among South Asians and Western Europeans, respectively). Ethnic differences emerged at young ages. South Asians aged 20–34 years had a similar prediabetes incidence as Europeans who were 15 years older (35–49 years), regardless of which prediabetes definition was used (WHO/DC 14.4% vs 15.7%; ADA 38.0% vs 33.0%).ConclusionPrediabetes incidence was substantially higher among non-European immigrants to Canada, highlighting the need for early prevention strategies in these populations.