Competing Risks Methods Research Articles

Impact of 2-staged stereotactic radiosurgery for treatment of brain metastases ≥ 2 cm

OBJECTIVE Stereotactic radiosurgery (SRS) is the primary modality for treating brain metastases. However, effective radiosurgical control of brain metastases ≥ 2 cm in maximum diameter remains challenging and is associated with suboptimal local control (LC) rates of 37%-62% and an increased risk of treatment-related toxicity. To enhance LC while limiting adverse effects (AEs) of radiation in these patients, a dose-dense treatment regimen using 2-staged SRS (2-SSRS) was used. The objective of this study was to evaluate the efficacy and toxicity of this treatment strategy. METHODS Fifty-four patients (with 63 brain metastases ≥ 2 cm) treated with 2-SSRS were evaluated as part of an institutional review board-approved retrospective review. Volumetric measurements at first-stage stereotactic radiosurgery (first SSRS) and second-stage SRS (second SSRS) treatments and on follow-up imaging studies were determined. In addition to patient demographic data and tumor characteristics, the study evaluated 3 primary outcomes: 1) response at first follow-up MRI, 2) time to local progression (TTP), and 3) overall survival (OS) with 2-SSRS. Response was analyzed using methods for binary data, TTP was analyzed using competing-risks methods to account for patients who died without disease progression, and OS was analyzed using conventional time-to-event methods. When needed, analyses accounted for multiple lesions in the same patient. RESULTS Among 54 patients, 46 (85%) had 1 brain metastasis treated with 2-SSRS, 7 patients (13%) had 2 brain metastases concurrently treated with 2-SSRS, and 1 patient underwent 2-SSRS for 3 concurrent brain metastases ≥ 2 cm. The median age was 63 years (range 23-83 years), 23 patients (43%) had non-small cell lung cancer, and 14 patients (26%) had radioresistant tumors (renal or melanoma). The median doses at first and second SSRS were 15 Gy (range 12-18 Gy) and 15 Gy (range 12-15 Gy), respectively. The median duration between stages was 34 days, and median tumor volumes at the first and second SSRS were 10.5 cm3 (range 2.4-31.3 cm3) and 7.0 cm3 (range 1.0-29.7 cm3). Three-month follow-up imaging results were available for 43 lesions; the median volume was 4.0 cm3 (range 0.1-23.1 cm3). The median change in volume compared with baseline was a decrease of 54.9% (range -98.2% to 66.1%; p < 0.001). Overall, 9 lesions (14.3%) demonstrated local progression, with a median of 5.2 months (range 1.3-7.4 months), and 7 (11.1%) demonstrated AEs (6.4% Grade 1 and 2 toxicity; 4.8% Grade 3). The estimated cumulative incidence of local progression at 6 months was 12% ± 4%, corresponding to an LC rate of 88%. Shorter TTP was associated with greater tumor volume at baseline (p = 0.01) and smaller absolute (p = 0.006) and relative (p = 0.05) decreases in tumor volume from baseline to second SSRS. Estimated OS rates at 6 and 12 months were 65% ± 7% and 49% ± 8%, respectively. CONCLUSIONS 2-SSRS is an effective treatment modality that resulted in significant reduction of brain metastases ≥ 2 cm, with excellent 3-month (95%) and 6-month (88%) LC rates and an overall AE rate of 11%. Prospective studies with larger cohorts and longer follow-up are necessary to assess the durability and toxicities of 2-SSRS.

Patterns of spread and prognostic implications of lung cancer metastasis in an era of driver mutations.

In the present study, we examined the pattern of metastatic spread in patients with advanced non-small-cell lung cancer (nsclc) and the effect of EGFR mutations. Patients were identified from a provincial cancer registry, and individual medical records were reviewed. Patients were included if they had stage iv nsclc and underwent diagnostic EGFR mutation testing. Patients were divided into EGFR mutation-positive (EGFR+) and EGFR wild type (wt) cohorts. The primary endpoint was the cumulative incidence for each metastatic site: lung, bone, brain, liver, adrenal glands, distant nodes, and other. Cumulative incidence curves were estimated using a competing-risks method. The secondary outcome was survival. Of the 543 identified patients, 121 (22.3%) tested as EGFR+, and 422 (77.7%) tested as EGFR wt. The incidence of brain (39.2% vs. 28.2%, p = 0.038) and lung (61.2% vs. 51.0%, p = 0.048) metastasis was higher in the EGFR+ cohort than in the EGFR wt cohort. In the EGFR+ cohort, a higher incidence of liver metastasis was associated with the exon 21 mutation subtype than with the exon 19 deletion subtype [23% vs. 7%, p < 0.01; hazard ratio (hr): 3.47]. Median survival was significantly longer for the EGFR+ cohort than for the EGFR wt cohort (22.4 months vs. 7.9 months, p < 0.001). In multivariable analysis, brain (hr: 1.73), liver (hr: 1.69), and bone (hr: 1.89) metastases were associated with worse survival. Rates of lung and brain metastases are higher in EGFR mutation carriers, even when adjusted for differences in survival. Brain, liver, and bone metastases are independent negative prognostic factors for survival.

Outcome following radiotherapy for head and neck basal cell carcinoma with ‘aggressive’ features

ObjectivesThe literature demonstrates that ‘aggressive’ head-and-neck basal cell carcinomas (HN-BCC) have a higher than expected relapse rate with unfavorable outcomes. We report outcomes following definitive (dRT) or post-operative radiotherapy (PORT) for these tumors. MethodsWe reviewed all HN-BCC patients with ‘aggressive’ features (primary lesions diameter >10mm, >2 recurrences, or extra-cutaneous extension), treated with megavoltage dRT or PORT between 1998 and 2013. Loco-regional control (LRC) and relapse-free survival (RFS) were estimated using the competing risk method, and overall survival (OS) by Kaplan-Meier method. Univariable analysis explored factors associated with relapse. ResultsA total of 108 histologically confirmed ‘aggressive’ HN-BCC patients were identified, including 38 (35%) presenting de novo and 70 (65%) treated for recurrence (rBCC). dRT was offered to 72 (66.7%) patients and PORT to 36 (33.3%). Median follow-up was 3.5years. Actuarial 3-year LRC, RFS, and OS were 87% (95% confidence interval: 77–92), 82% (72–89), and 87% (80–94), respectively. LRC rates for dRT and PORT were similar [hazard ratio (HR) 0.61 (0.17–2.23), p=0.46]. Factors associated with higher risk of relapse were: rBCC [HR 7.96 (1.03–61.71), p=0.047], ‘H-zone’ (mid face, eyes, and ears) location [HR 3.13 (1.07–9.19), p=0.04], tumor size [HR 1.32 (1.08–1.6), p=0.006], nodal involvement [HR 3.68 (1.11–12.2), p=0.03] and stage [HR 3.13 (1.19–8.26), p=0.02]. ConclusionRT is an effective treatment for ‘aggressive’ HN-BCC when used as a definitive modality or as PORT. Non-surgical management with definitive radiotherapy provides an alternative effective option if surgery is not used.

Stereotactic body radiation vs. intensity-modulated radiation for unresectable pancreatic cancer

Background: Stereotactic body radiation therapy (SBRT) is an emerging treatment option for unresectable pancreatic cancer, and is postulated to be more effective and less toxic than conventionally fractionated intensity modulated radiation therapy (IMRT).Material and methods: We retrospectively reviewed unresectable stage I–III pancreatic adenocarcinoma treated from 2008 to 2016 at our institution with SBRT (five fractions, 30–33 Gy) or IMRT (25–28 fractions, 45–56 Gy with concurrent chemotherapy). Groups were compared with respect to overall survival (OS), local and distant failure, and toxicity. Log-rank test and Cox proportional hazards regression model, and competing risks methods were used for univariate and multivariate analysis.Results: SBRT patients (n = 44) were older than IMRT (n = 226) patients; otherwise there was no significant difference in baseline characteristics. There was no significant difference in OS or local or distant failure. There was no significant difference in rates of subsequent resection (IMRT =17%, SBRT =7%, p = .11). IMRT was associated with more acute grade 2+ gastrointestinal toxicity, grade 2+ fatigue, and grade 3+ hematologic toxicity (p = .008, p < .0001, p = .001, respectively).Conclusions: In this analysis, SBRT achieves similar disease control outcomes as IMRT, with less acute toxicity. This suggests SBRT is an attractive technique for pancreatic radiotherapy because of improved convenience and tolerability with equivalent efficacy. However, the lack of observed advantages in disease control with this moderate-dose SBRT regimen may suggest a role for increasing SBRT dose, if this can be accomplished without significant increase in toxicity.

Risk of Second Primary Malignancies in Patients With Follicular Lymphoma: A United States Population-based Study.

With the improving outcomes of patients with follicular lymphoma (FL), it is imperative to focus on survivorship issues, including the development of second primary malignancies (SPMs). We used a large US database to measure the risk of SPMs among FL survivors. We used the Surveillance, Epidemiology, and End Results-13 registry to identify FL patients from 1992 to 2011. We calculated the risk of SPMs, developing≥ 6 months after diagnosis, using the standardized incidence ratio (SIR) and absolute excess risk. We calculated the cumulative incidence of SPMs using the competing risk method and risk factors for SPMs using univariate and multivariate methods. Of a total of 15,517 patients with FL followed up for a median of 71 months, 1540 (9.9%) developed SPMs, with a SIR of 1.08 and absolute excess risk of 11.3 per 10,000 person-years. A significantly increased risk was noted for Hodgkin lymphoma (SIR, 5.85), acute myeloid leukemia (SIR, 4.88), and the following sites: oral cavity and pharynx (SIR, 1.43), stomach (SIR, 1.43), lung and bronchus (SIR, 1.35), melanoma of skin (SIR, 1.38), other nonepithelial cancers of the skin (SIR, 2.88), urinary bladder (SIR, 1.24), and kidney/renal pelvis (SIR, 1.43). The cumulative incidence of SPMs was 11.06% at 10 years. Multivariate regression showed that age > 65 years (SIR, 1.57; P< .001), male gender (SIR, 1.43; P< .001), and receipt of radiation (SIR, 1.24; P= .001) predicted a higher rate of SPMs. Patients with FL have increased risk of both hematologic and solid malignancies. Risk factors for SPMs include advanced age, male gender, and receipt of radiation therapy.

Refining Patient Selection for Reirradiation of Head and Neck Squamous Carcinoma in the IMRT Era: A Multi-institution Cohort Study by the MIRI Collaborative

The therapeutic ratio of reirradiation for recurrent or second primary (RSP) squamous carcinoma of the head and neck may be improved in the intensity modulated radiation therapy (IMRT) era. However, patient selection for reirradiation remains challenging. We performed a multi-institution cohort study to investigate modern outcomes after IMRT-based reirradiation and to identify prognostic subgroups. Patients with RSP squamous carcinoma originating in a previously irradiated field (≥40Gy) who underwent reirradiation with IMRT (≥40Gy re-IMRT) were included. Locoregional failure and late toxicity were calculated using the Gray competing risk method. Cox proportional hazards regression was used to identify factors associated with overall survival (OS). Factors associated with OS were entered into a recursive partitioning analysis (RPA) for OS. From 7 institutions, 412 patients were included. The median dose of re-IMRT was 60Gy, and the median time between RT courses was 2.4years. Chemotherapy was used in 76% of patients. The rates of grade ≥3, grade ≥4, and grade 5 acute toxicities were 19%, 4.4%, and 1.2%, respectively. The 2-year cumulative incidence of grade ≥3 late toxicity adjusted for the competing risks of recurrence or death was 14.2%. RPA identified 3 prognostic subgroups with distinct and homogenous OS (P<.001): class I included patients >2years from their initial course of RT with resected tumors (2-year OS, 61.9%); class II included patients >2years with unresected tumors or those ≤2years and without feeding tube or tracheostomy dependence (2-year OS, 40.0%), and the remaining patients formed class III (2-year OS, 16.8%). Fifty-nine percent of class III patients underwent postoperative re-irradiation. This study informs outcomes and expectations with IMRT-based reirradiation. The RPA classification identifies 3 distinct subgroups, which can guide patient selection for therapy and clinical trial design. RPA class III patients are not ideal candidates for protracted chemoradiation regardless of resection status.

Long-term follow-up of bioprosthetic aortic valve replacement in patients aged ≤60 years

ObjectiveTo address the long-term durability of bioprostheses used for aortic valve replacement (AVR) in adult patients aged ≤60 years at the time of surgery. MethodsThrough a retrospective review of a prospectively collected database, we identified 416 bioprosthetic AVRs performed between 1977 and 2013. A prospective follow-up of valve-related and non–valve-related events was performed. ResultsFollow-up was 98.5% complete (2423.1 patient-years; average, 6 ± 5.5 years). At 15 years, overall survival was 62.1 ± 4.4%; freedom from valve-related death was 97.1 ± 1.6%. There were 68 SVD events (11.9 ± 28.8 years after surgery). Freedom from SVD at 15 years was 48.7 ± 5.5% for Kaplan-Meier analysis and 61.4 ± 4.3% for competing-risks analysis. After stratification into age subgroups (<40 years, ≥40 and <50 years, and ≥50 and ≤60 years), we observed no significant difference in freedom from SVD (P = .50). The average delay to SVD was not statistically different among subgroups (P = .30). There were 57 reoperations for SVD (11.8 ± 5.2 years after implantation). The 15 year freedom from reoperation for SVD was 55.4 ± 5.6% by Kaplan-Meier analysis and 67.1 ± 4.2% by competing-risks analysis. After stratification by age, freedom from reoperation for SVD was comparable (P = .13). Freedom from any valve-related complication or death was 42 ± 5% by Kaplan-Meier analysis and 54.4 ± 4.1% by competing-risks analysis. ConclusionsThe lifetime risk of SVD is considerable in patients aged ≤60 years at the time of bioprosthesis implantation. Nonetheless, durability remains consistent during the first decade; additional data are required for the second decade. Patients' information is pivotal for valve choice (competing-risks method).

Attrition and Mortality of Children Receiving Antiretroviral Treatment through the Universal Coverage Health Program in Thailand

To assess mortality and loss to follow-up of children with HIV infection who started antiretroviral therapy (ART) through the Universal Coverage Health Program (UC) in Thailand. Children with HIV infection who initiated ART at age <15 years through the UC between 2008 and 2013 were included in the analysis. Death was ascertained through linkage with the National Death Registry. A competing-risks method was used to calculate subdistribution hazard ratios (SHRs) of predictors for loss to follow-up. Death was considered a competing risk. Cox proportional hazards models were used to assess predictors of mortality. A total of 4618 children from 497 hospitals in Thailand were included in the study. Median age at ART initiation was 9 years (IQR, 6-12 years), and the median duration of tracking was 4.1 years (a total of 18 817 person-years). Three hundred and ninety-five children (9%) died, for a mortality rate of 2.1 (95% CI, 1.9-2.3) per 100 person-years, and 525 children (11%) were lost to follow-up, for a lost to follow-up rate of 2.9 (95% CI, 2.7-3.2) per 100 person-years. The cumulative incidence of loss to follow-up increased from 4% at 1 year to 8.8% at 3 years. Children who started ART at age ≥12 years were at the greatest risk of loss to follow-up. The probability of death was 3.2% at 6 months and 6.4% at 3 years. Age ≥12 years at ART initiation, lower baseline CD4%, advanced HIV staging, and loss to follow-up were associated with mortality. The Thai national HIV treatment program has been very effective in treating children with HIV infection, with low mortality and modest rates of loss to follow-up.

Association of Glycemic Status During Progression of Chronic Kidney Disease With Early Dialysis Mortality in Patients With Diabetes.

Although early trials suggested that intensive glycemic targets reduce the number of complications with diabetes, contemporary trials indicate no cardiovascular benefit and potentially higher mortality risk. As patients with advanced chronic kidney disease (CKD) transitioning to treatment with dialysis were excluded from these studies, the optimal glycemic level in this population remains uncertain. We hypothesized that glycemic status, defined by hemoglobin A1c (HbA--1c) and random glucose levels, in the pre-end-stage renal disease (ESRD) period is associated with higher 1-year post-ESRD mortality among patients with incident diabetes who have ESRD. Among 17,819 U.S. veterans with diabetic CKD transitioning to dialysis from October 2007 to September 2011, we examined the association of mean HbA--1c and random glucose levels averaged over the 1-year pre-ESRD transition period with mortality in the first year after dialysis initiation. All-cause mortality hazard ratios (HRs) were estimated using multivariable survival models. Secondary analyses examined cardiovascular mortality using competing risks methods. HbA--1c levels ≥8% (≥64 mmol/mol) were associated with higher mortality in the first year after dialysis initiation (reference value 6% to <7% [42-53 mmol/mol]): adjusted HRs [aHRs] 1.19 [95% CI 1.07-1.32] and 1.48 (1.31-1.67) for HbA--1c 8% to <9% [64-75 mmol/mol] and ≥9% [≥75 mmol/mol], respectively). Random glucose levels ≥200 mg/dL were associated with higher mortality (reference value 100 to <125 mg/dL): aHR 1.34 [95% CI 1.20-1.49]). Cumulative incidence curves showed that incrementally higher mean HbA--1c and random glucose levels were associated with increasingly higher cardiovascular mortality. In patients with diabetes and CKD transitioning to dialysis, higher mean HbA--1c and random glucose levels during the pre-ESRD prelude period were associated with higher 1-year post-ESRD mortality. Clinical trials are warranted to examine whether modulating glycemic status improves survival in this population.

Ovarian Function Recovery During Anastrozole in Breast Cancer Patients With Chemotherapy-Induced Ovarian Function Failure

Aromatase inhibitors (AIs) are given as adjuvant therapy for hormone receptor-positive breast cancer in postmenopausal women, also to those with chemotherapy-induced ovarian function failure. The current analysis reports on endocrine data of patients with chemotherapy-induced ovarian function failure who were included in the phase III DATA study assessing different durations of adjuvant anastrozole after tamoxifen. We identified all patients with chemotherapy-induced ovarian function failure. Women who underwent a bilateral ovariectomy or used luteinizing hormone-releasing hormone agonists before random assignment were excluded. Plasma estradiol and follicle-stimulating hormone levels were monitored until 30 months after random assignment at local laboratories. We aimed to determine the ovarian function recovery (OFR) rate during AI use by the cumulative incidence competing risk method and analyzed the trend of estradiol levels during AI use by a nested case-control approach in which a subset of control subjects were compared with the OFR patients excluding the value at OFR diagnosis. The 329 eligible patients had a median age of 50.0 years (range = 45-57 years) at random assignment. Thirty-nine patients developed OFR, corresponding with a 30-month recovery rate of 12.4%. Of these, 11 (28.2%) were age 50 years or older at AI initiation. The estradiol level decreased statistically significantly by 37.8% (95% CI = 27.4% to 46.7%) over the initial 30 months of AI treatment in both groups. However, the estradiol levels in the women who experienced OFR remained statistically significantly higher (difference = 20.6%, 95% CI = 2.0% to 42.7%) prior to OFR diagnosis compared with those who did not experience OFR. The risk of OFR during AI treatment in breast cancer patients with chemotherapy-induced ovarian function failure is relevant, even beyond 45 years. Furthermore, women experiencing OFR had statistically significant higher estradiol levels during AI treatment (before OFR) than those without, with potential consequences regarding efficacy.

Comparison of single- and five-fraction schedules of stereotactic body radiation therapy for central lung tumours: a single institution experience.

Background:Stereotactic body radiation therapy (SBRT) is a treatment option for patients with early-stage non-small cell lung cancer who are medically inoperable or decline surgery. Here we compare the outcome of patients with centrally located lung tumours who underwent either single fraction (SF)- or five-fraction (FF-) SBRT at a single institution over 5 years.Methods:Between January 2009 and October 2014, patients with centrally located lung tumours who underwent SBRT were included in this study. Data were retrospectively collected using an institutional review board-approved database. For analysis, the Kaplan–Meier method and competing risks method were used.Results:In total, 11 patients received 26–30 Gy in 1 fraction, whereas 31 patients received 50–60 Gy (median 55 Gy) in 5 fractions. After a median follow-up of 12 months for SF-SBRT and 17 months for FF-SBRT groups (p = 0.64), 1-year overall survival rates were 82 and 87%, respectively. SF- and FF-SBRT groups showed no significant difference in grade 3+ toxicity (p = 0·28). The only grade 4 toxicity (n = 1) was reported in the SF-SBRT group. All toxicities occurred >12 months after the SBRT.Conclusions:SF- and FF-SBRT have comparable overall survival. SF-SBRT may have some utility for patients unable to have multi-fraction SBRT.

Delayed lower cranial neuropathy after oropharyngeal intensity-modulated radiotherapy: A cohort analysis and literature review.

The purpose of this study was to examine swallowing-related lower cranial nerve palsy (LCNP) in oropharyngeal cancer (OPC) survivors after intensity-modulated radiotherapy (IMRT). Patients treated with definitive IMRT (66-72 Gy) were pooled from institutional trial databases. Prospective analyses on parent trials included videofluoroscopy, clinical LCNP examination, and questionnaires pre-IMRT, 6 months post-IMRT, 12 months post-IMRT, and 24 months post-IMRT. Time-to-event and incidence of LCNP was estimated with competing risk methods. Literature review (1977-2015) summarized published LCNP outcomes. Three of 59 oropharyngeal cancer survivors with a minimum 2-year follow-up developed hypoglossal palsy ipsilateral to the index tumor (median latency 6.7 years; range 4.6-7.6 years). At a median of 5.7 years, cumulative incidence of LCNP was 5%. LCNP preceded progressive dysphagia in all cases. Published studies found median incidence of radiation-associated LCNP was 10.5% after NPC, but no OPC cancer-specific estimate. Although uncommon, the potential for late LCNP preceding swallowing deterioration highlights the importance of long-term functional surveillance in OPC survivorship.

Competing risks analysis of microsatellite instability as a prognostic factor in colorectal cancer

Despite an extensive literature suggesting that high microsatellite instability (MSI-H) enhances survival and protects against recurrence after colorectal cancer resection, such effects remain controversial as many studies show only a weak bivariate association or no multivariable association with outcome. This study examined the relationship between MSI status and colorectal cancer outcomes with adjustment for death from other causes as a competing risk. A hospital database of patients following colorectal cancer resection was interrogated for clinical, operative, pathology, adjuvant therapy and follow-up information. MSI-H status was determined by immunohistochemistry for mismatch repair protein deficiency. The cumulative incidence of recurrence and colorectal cancer-specific death was evaluated by competing risks methods. Among 1009 patients who had a resection between August 2002 and December 2008, and were followed to at least December 2013, there were 114 (11·3 per cent) with MSI-H (72·8 per cent aged at least 70 years; 63·2 per cent women). After potentially curative resection, with adjustment for non-colorectal cancer death as a competing risk and adjustment for 22 clinical, operative and pathological variables, there was no association between MSI-H and recurrence (hazard ratio (HR) 0·81, 95 per cent c.i. 0·42 to 1·57) or colorectal cancer-specific death (HR 0·73, 0·39 to 1·35) in this patient population. For palliative resections, there was no association between MSI-H and colorectal cancer-specific death (HR 0·65, 0·21 to 2·04). MSI-H was associated with non-colorectal cancer death after both curative (HR 1·55, 1·04 to 2·30) and palliative (HR 3·80, 1·32 to 11·00) resections. Microsatellite instability status was not an independent prognostic variable in these patients.

Evaluation of prognostic factors effect on survival time in patients with colorectal cancer, based on Weibull Competing-Risks Model.

The aim of this study was to assess the association between survival of patients with colorectal cancer and prognostic factors in a competing risk parametric model using Weibull distribution. The prognosis of colorectal cancer is relatively good in terms of survival time. In many prognostic studies, patients may be exposed to several types of competing events. These different causes of death are called competing risks. Data was recorded from 372 patients with colorectal cancer who registered in the Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences (Tehran, Iran) from 2004 to 2015 in a retrospective study. Analysis was performed using competing risks model and Weibull distribution. Software used for data analysis was R, and significance level was regarded as 0.05. The result indicated that, at the end of follow-up, 111 (29.8%) deaths were from colorectal cancer and 14 (3.8%) deaths were due to other diseases. The average body mass index (BMI) was 24.61(SD 3.98). The mean survival time for a patient in 372 was 62.05(SD 48.78) month with median equals to 48 months. According to competing-risks method, only stageIII (HR, 1.69; 95% CI, 1.246-2.315 ), stageIV( HR, 4.51; 95% CI,2.91-6.99 ) and BMI( HR, 0.96; 95% CI, 0.96-0.975) have a significant effect on patient's survival time. This study indicated pathologic stage (III,IV) and BMI as the prognosis, using a Weibull model with competing risks analysis, while other models without the competing events lead to significant predictors which may be due to over-estimation.

Linguistic Isolation and Access to the Active Kidney Transplant Waiting List in the United States.

Waitlist inactivity is a barrier to transplantation, because inactive candidates cannot receive deceased donor organ offers. We hypothesized that temporarily inactive kidney transplant candidates living in linguistically isolated communities would be less likely to achieve active waitlist status. We merged Organ Procurement and Transplantation Network/United Network for Organ Sharing data with five-digit zip code socioeconomic data from the 2000 US Census. The cumulative incidence of conversion to active waitlist status, death, and delisting before conversion among 84,783 temporarily inactive adult kidney candidates from 2004 to 2012 was determined using competing risks methods. Competing risks regression was performed to characterize the association between linguistic isolation, incomplete transplantation evaluation, and conversion to active status. A household was determined to be linguistically isolated if all members ≥14 years old speak a non-English language and also, speak English less than very well. A total of 59,147 candidates (70% of the study population) achieved active status over the study period of 9.8 years. Median follow-up was 110 days (interquartile range, 42-276 days) for activated patients and 815 days (interquartile range, 361-1244 days) for candidates not activated. The cumulative incidence of activation over the study period was 74%, the cumulative incidence of death before conversion was 10%, and the cumulative incidence of delisting was 13%. After adjusting for other relevant covariates, living in a zip code with higher percentages of linguistically isolated households was associated with progressively lower subhazards of activation both in the overall population (reference: <1% linguistically isolated households; 1%-4.9% linguistically isolated: subhazard ratio, 0.89; 95% confidence interval, 0.86 to 0.93; 5%-9.9% linguistically isolated: subhazard ratio, 0.83; 95% confidence interval, 0.80 to 0.87; 10%-19.9% linguistically isolated: subhazard ratio, 0.76; 95% confidence interval, 0.72 to 0.80; and ≥20% linguistically isolated: subhazard ratio, 0.71; 95% confidence interval, 0.67 to 0.76) and among candidates designated temporarily inactive due to an incomplete transplant evaluation. Our findings indicate that candidates residing in linguistically isolated communities are less likely to complete candidate evaluations and achieve active waitlist status.

Stereotactic body radiation vs. intensity-modulated radiation for unresectable pancreatic cancer.

353 Background: Stereotactic body radiation therapy (SBRT) is an emerging treatment option for unresectable pancreatic cancer, and may be more effective and less toxic than intensity modulated radiation therapy (IMRT). Methods: We retrospectively reviewed unresectable stage I-III pancreatic adenocarcinoma treated with SBRT (5 fractions, 30-33Gy) or IMRT (25-28 fractions, 45-56Gy with concurrent chemotherapy) between 2008-2016 at our institution. The groups were compared with respect to overall survival (OS), local failure (LF), distant failure (DF), any failure (AF), proportion of patients becoming resectable, and incidence of acute toxicity. Competing risks methods were used for univariate (UVA) and multivariate analysis (MVA) for LF, DF and AF. All endpoints were calculated from end of RT. Results: Median follow-up for surviving patients was 12.9 months. 44 patients received SBRT and 226 patients received IMRT. Patients who received SBRT were older (45% vs 29% &gt; 70 years old, p = 0.05). Otherwise there was no significant difference in baseline characteristics, including stage and duration of induction chemotherapy. On MVA, there was no significant difference in OS, LF, DF, or AF between IMRT and SBRT (p = 0.73, 0.81, 0.44, and 0.39 respectively). Median OS was 15.7 months, and the 1-year rate of LF was 34.4% for SBRT and 30.2% for IMRT. Response to induction chemotherapy was associated with longer OS (p = 0.03). There was no significant difference in the proportion of patients who were subsequently resected between IMRT (17%) and SBRT (7%; p = 0.11). Significantly more IMRT patients experienced acute G2+ GI toxicity (24% vs. 7%, p = 0.008), G2+ fatigue (42% vs. 7%, p &lt; 0.0001), and G3+ hematologic toxicity (26% vs. 5%, p = 0.001) compared to SBRT. Conclusions: SBRT achieves similar disease control outcomes as IMRT, and is associated with less acute toxicity. This data suggests SBRT is an attractive technique for pancreatic radiotherapy because of improved convenience and tolerability with equivalent efficacy. However, the lack of observed advantages in disease control with this moderate-dose SBRT regimen suggests a role for increasing SBRT dose, if this can be accomplished without significant increase in toxicity.

Overestimation of the risk of revision with Kaplan-Meier presenting the long-term outcome of total hip replacement in older patients.

The purpose of the present study was (i) to review the long-term outcome of cemented Charnley total hip replacements (THRs) performed by 1 surgeon (GH), 20 to 42 years ago, in patients ≥60 years, using both the Kaplan-Meier (KM) and the cumulative incidence (CI) methods, and (ii) to compare the estimations of the 2 statistical methods. We evaluated the outcome of 306 consecutive primary cemented THRs that were performed in 265 patients. The final clinical, radiographic assessment and satisfaction of living patients were also included. The survivorship was estimated with the use of KM and CI methods and the relative difference between their estimations was calculated. Living patients' final clinical results were significantly improved in comparison with respective preoperative ones, and all the acetabular and 91% of femoral components considered as well fixed. 95% of these patients reported satisfaction. The risk of revision at 25 years, with revision for aseptic loosening for 1 or both components as the endpoint, with 21 hips at risk, assessed with KM analysis was 6.9% and with CI approach was 3.9%. The relative difference between KM and CI estimations was increasing during follow-up, reaching up to 76.8% at 25 years. We concluded that fixation of implants with cement in older patients had satisfactory long-term results and can serve as a benchmark with which to compare newer fixation methods (hybrid and uncemented) and materials. However, KM method, in studies that include older population with long-term follow-up, may significantly overestimate the risk of revision and clinicians could consider using besides the cumulative incidence of competing risk method.

Stereotactic Body Radiation Therapy in Octo- and Nonagenarians for the Treatment of Early-Stage Lung Cancer

To determine the safety and efficacy of lung stereotactic body radiation therapy (SBRT) in octo- and nonagenarians and to compare their outcomes with those of younger patients. Patients with primary lung cancer treated with SBRT were identified from a multi-institutional (5 institutions) database of 1083 cases. Details of patient factors, treatment specifics, toxicity, and clinical outcomes were extracted from the database. All events were calculated from the end of radiation therapy. Estimates of local recurrence, regional recurrence, and distant metastases were calculated using the competing risk method. Cause-specific survival (CSS) and overall survival (OS) were calculated using the Kaplan-Meier method. Outcomes were compared for those aged <70, 70 to 79, and ≥80years. Univariable and multivariable analyses were performed to determine associations with CSS and OS in patients aged ≥80years. The median (range) follow-up was 1.7 (1-10) years, and median age was 75 (41-94) years. There were 305 patients aged <70years (28%), 448 aged 70 to 79years (41%), and 330 aged ≥80years (30%). There was no difference in 2-year local recurrence (4.2% vs 5.4% vs 3.7%, respectively, P=.7), regional recurrence (10.4% vs 7.8% vs 5.3%, P=.1), distant metastases (12.2% vs 7.7% vs 9.5%, P=.2), or CSS (90.6% vs 90.3% vs 90.4%, P=.6). Those aged ≥80years had significantly lower 2-year OS (73.6% vs 67.2% vs 63.3%, P<.01). The grade 3+pneumonitis rate was 1.3% versus 1.6% versus 1.5% (P=1.0) in patients aged <70, 70 to 79, and ≥80years, respectively. The 90-day mortality rates for patients aged <70, 70 to 79, and ≥80years were 1.3%, 2.5%, and 2.4% (P=.01), respectively. In patients aged ≥80years OS was associated with T category (hazard ratio 1.7; P<.01). Stereotactic body radiation therapy is a safe treatment modality in elderly patients (aged ≥80years). Despite larger tumor volumes, the tumor control outcomes were comparable to those in younger patients treated with SBRT. All patients with early-stage lung cancer, regardless of age, should be considered for treatment with SBRT.

Variation in Access to Kidney Transplantation Across Renal Programs in Ontario, Canada.

In the United States, kidney transplant rates vary significantly across end-stage renal disease (ESRD) networks. We conducted a population-based cohort study to determine whether there was variability in kidney transplant rates across renal programs in a health care system distinct from the United States. We included incident chronic dialysis patients in Ontario, Canada, from 2003 to 2013 and determined the 1-, 5-, and 10-year cumulative incidence of kidney transplantation in 27 regional renal programs (similar to U.S. ESRD networks). We also assessed the cumulative incidence of kidney transplant for "healthy" dialysis patients (aged 18-50 years without diabetes, coronary disease, or malignancy). We calculated standardized transplant ratios (STRs) using a Cox proportional hazards model, adjusting for patient characteristics (maximum possible follow-up of 11 years). Among 23 022 chronic dialysis patients, the 10-year cumulative incidence of kidney transplantation ranged from 7.4% (95% confidence interval [CI] 4.8-10.7%) to 31.4% (95% CI 16.5-47.5%) across renal programs. Similar variability was observed in our healthy cohort. STRs ranged from 0.3 (95% CI 0.2-0.5) to 1.5 (95% CI 1.4-1.7) across renal programs. There was significant variation in kidney transplant rates across Ontario renal programs despite patients having access to the same publicly funded health care system.

OA24.07 The Impact of Population Heterogeneity on the Efficacy of SBRT to the Lung

Stereotactic Body Radiation Therapy (SBRT) is the standard of care for medically inoperable patients with early-stage non-small cell lung cancer (NSCLC). However, NSCLC is comprised of several histological subtypes and the impact of this heterogeneity on SBRT treatments has yet to be established. We analyzed 740 early-stage NSCLC patients treated definitively with SBRT from 2003 through 2015. We calculated cumulative incidence curves using the competing risk method and identified predictors of local failure using Fine and Gray regression. Overall, 72 patients had a local failure with a cumulative incidence of local failure at three years of 11.8%. On univariate analysis, squamous histology, younger age, fewer medical comorbidities, higher BMI, higher PET SUV, central tumors and lower radiation dose were associated with an increased risk of local failure. On multivariable analysis, squamous histology (HR 2.4 p = 0.008) was the strongest predictor of local failure. Patients with squamous cancers fail SBRT at a significantly higher rate than those with adenocarcinomas or NSCLC-not otherwise specified, with three-year cumulative incidences of local failure of 18.9% (95% CI= 12.7-25.1%), 8.7% (95% CI= 4.6-12.8%), 4.1% (95% CI= 0-9.6%), respectively. Our results demonstrate an increased rate of local failure after SBRT in patients with squamous cell carcinoma. Standard approaches for radiotherapy that demonstrate efficacy for a population may not achieve optimal results for individual patients. Establishing the differential dose-responses of SBRT across histological groups is likely to improve efficacy and inform ongoing and future studies that aim to expand indications for SBRT.