e22634 Background: Prostate, pancreatic, and ovarian cancer are malignancies with known high prevalences of pathogenic germline variants strongly associated with development of these malignancies. The implications for germline genetic testing (GGT) are significant and can have a substantial impact on patient care, treatment decisions, and prognostication. Furthermore, GGT can identify unaffected family members who may benefit from cancer screening and/or interventions to reduce their risk of various cancers. As of 2019, National Comprehensive Cancer Network (NCCN) guidelines recommend universal GGT for high/very-high risk localized or metastatic prostate cancer, exocrine pancreatic cancer, and epithelial ovarian cancer. Despite this recommendation, low rates of genetic counseling (GC) referrals and GGT are well-recognized concerns within the field. Therefore, we sought to determine the rates of GC referrals and GGT at our rural-based institution for the aforementioned cancers. Methods: Following IRB approval, we identified all adult patients diagnosed in our health system between January 2020 and January 2024 with high/very-high risk localized prostate cancer, node-positive/metastatic prostate cancer, epithelial ovarian cancer, and exocrine pancreatic cancer. Those who previously had undergone GGT for hereditary cancer evaluation were excluded. Via retrospective review of patient electronic health records, we captured demographics, disease-specific variables, and data regarding GC appointments, patient access, and GGT by cancer type. Results: Six hundred twenty-one patients met study inclusion criteria: (55% prostate, 31% pancreatic, 13% ovarian). Our sample was 98% White, 74% male, 53% current/former smoker, had a median age of 71 years, and 63% lived in a non-metropolitan area. Most patients had stage III or IV disease (72%). In total, 168 (27%) had a GC order (16% prostate, 26% pancreatic, 75% ovarian; p < 0.01), 106 (17%) completed a GC appointment (9.6% prostate, 13% pancreatic, 58% ovarian; p < 0.01), and 106 (17%) underwent GGT (9.6% prostate, 14% pancreatic, 55% ovarian; p< 0.01). Median time from diagnosis to GC appointment was 129 days (148 prostate, 115 pancreatic, 129 ovarian; p = 0.3). Most GC orders were placed by medical oncology (72%), followed by radiation oncology (17%). Conclusions: Despite clear NCCN recommendations for universal testing for high/very-high risk localized or metastatic prostate cancer, pancreatic cancer, and ovarian cancer, our institution has very low rates of GC referrals and GGT. Ovarian cancer had the highest rates of GC and GGT (58% and 55%, respectively), rates still far from optimal. Despite low rates of GGT in these cancers, our data appear consistent with national trends for GGT (10% prostate, 22% pancreatic, 55% ovarian). A future study will identify barriers to GC and GGT and propose strategies to increase GGT rates at our institution.

9024 Background: Genomic oncology (GO) is central to diagnosis and management of patients with cancer. However, GO training is an unmet need for hematology/oncology (H/O) fellows. The Training Fellows in Genomic (TFIG) Working Group developed a team-based GO workshop, with goals of creating a “train-the-trainer” experience for faculty and improving fellows’ GO knowledge. Methods: Ten North American H/O fellowship programs participated in the TFIG pilot. Cross-disciplinary faculty (H/O fellowship program leaders [PL] with local GO faculty experts) participated in (2) 60-minute virtual “train-the-trainer” sessions on team-based learning (TBL) and GO content. Faculty then led (2) 120-minute case-based TBL workshops for fellows at their home institutions: 1) methodology and selection of cancer gene panels, and 2) result interpretation and clinical utility. Participating faculty and fellows were sent a post-workshop survey. Fellows received an additional follow-up survey seven months after workshop participation. Results: 96 fellows and 24 faculty participated in the TFIG workshop. 68 fellows (71%) and 21 faculty (88%) completed the post-workshop survey; 60 fellows (62%) completed the follow-up survey. In addition to H/O PL, workshop faculty included pathologists (n=2), genetic counselors (n=2), laboratory geneticists (n=2), medical geneticists (n=1), and genomics professors (n=1). Most (90%) felt train-the-trainer sessions were helpful for workshop preparation. All agreed/strongly agreed that the workshop will help fellows as practicing oncologists. All would recommend the workshop to other fellowship programs. While most fellows (88%) reported using GO in their clinics, 97% had no prior training during fellowship. The majority reported that their pre-workshop knowledge of GO was poor (31%) or fair (43%). Almost all (91%) agreed/strongly agreed that the workshop will help their clinical practice, and most (88%) would recommend this workshop to other fellows. At seven months post-workshop, more than half (52%) of fellows reported greater interactions with genetics professionals and increased use of web-based GO resources introduced during the workshop; 32% reported using knowledge gained during the workshop to educate others. Conclusions: Formalized training in GO is required for H/O practice and remains an unmet need for H/O fellows. Our TFIG pilot demonstrated that an interactive GO workshop is feasible through implementation of standardized faculty training and a case-based TBL format. Faculty found the “train-the-trainer” model helpful and noted TFIG content is effective and recommended for fellows. Fellows reported sustained improvements in GO knowledge, increased use of web-based GO tools explored during the workshop, and greater interdisciplinary engagement with GO experts. These findings support the TFIG model as a scalable and effective means to deliver expert-led, team-based GO training for H/O fellows.

e21598 Background: Uveal melanoma has an incidence of 5 cases/million in the United States, with higher incidence among men and those of fairer complexions. Stage I patients have a 20% risk of recurrence to a distant site. Those who do recur tend to have poor outcomes, with median overall survival ranging from 3 to 30 months. This disease has no proven adjuvant therapy. After initial definitive treatment, surveillance alone is typically the most common recommendation, but guidance for surveillance imaging is lacking. We sought to determine the incidence of uveal melanoma surveillance along with associated health-related outcomes in these patients in our rural healthcare system. Methods: Following Institutional Review Board approval, we identified patients with uveal melanoma diagnoses treated with definitive therapy who had ≥3 months of follow-up between January 2010 and January 2023. Patients with metastatic disease at presentation were excluded. Via retrospective review of electronic health records, we captured demographics, disease, treatment, and recurrence specific variables. Appropriate analysis was completed in R version 4.4.3 with a significance level of 0.05. Results: Fifty-seven patients met inclusion criteria. Of these, 31 (54%) were men, 57 (100%) were White, and their median age at diagnosis was 62 years. Ten (18%) underwent enucleation for initial definitive treatment, 39 (68%) had plaque/radiation therapy, 2 (4%) had transpupillary thermal therapy, and 6 (11%) had unknown primary treatment. Following initial definitive treatment, 22 (39%) patients had routine surveillance visits, and 11 (19%) had routine imaging of the liver to screen for metastatic disease. Married patients were less likely than unmarried to participate in surveillance, while the remaining demographic variables were not significantly different. In total, 16 (28%) patients had recurrence. Of these, 9 (56%) had oligometastatic disease defined as 1 to 3 sites of metastasis, and 14 (88%) had at least 1 liver metastasis. Ten of the 16 (63%) received either checkpoint therapy or bispecific T-cell engager immunotherapy. Seven of the 16 (44%) participated in some form of surveillance. Overall survival of those who had surveillance imaging was not significantly different from those who did not. Conclusions: A minority of patients with definitively treated uveal melanoma participated in surveillance visits, and even fewer completed regular screening imaging. Recurrence rates reflected the national average and frequently involved the liver. No differences in survival rates were seen between patients who underwent surveillance (with or without imaging) and those who were not surveilled. This study was limited by small sample size at a single institution. More research is needed to assess the utility of uveal melanoma surveillance.

e14705 Background: Increased use of immune checkpoint inhibitors (ICI) has resulted in a rise in immune related adverse events (irAEs), which many non-oncology clinicians may underrecognize. Controversy exists surrounding whether irAE presence has an impact on survival. Our primary goal was to evaluate the timing between detection to diagnosis of irAE, and determine the department responsible for making the irAE diagnosis. We also assess the incidence of single vs multisystem irAEs, impact of irAE on survival, and assess whether standard irAEs (s-irAEs) those diagnosed within 90 days of initial ICI administration vs delayed irAE (d-irAEs) those diagnosed >90 days impacts survival. Methods: We performed an IRB approved retrospective study of patients 18 years and older who received ICIs for a malignancy at Gundersen Health System between January 1, 2011 and December 31, 2021. Statistical analysis included Chi-square, Fisher’s Exact, and Wilcoxon rank sum tests and Kaplan-Meier survival analysis. All analysis was completed in R version 4.2.3 with a p-value <0.05 considered significant. Results: Our study included 664 patients who were 99.6% white, 60% male, and an average age of 67 years. Median Charlson Comorbidity Index was 10. There were 245 (36.8%) patients with at least 1 irAE, and 62 (9.3%) with a multisystem irAE. While 28 (11%) irAEs were initially detected by non-oncology providers, only 10 (4.1%) irAEs were diagnosed by a non-oncology department. Median time (days) from symptoms to diagnosis was 3 for those diagnosed in non-oncology departments and 0 for those diagnosed in oncology (p<0.01). A total of 142 (58.0%) s-irAEs were detected with grades 1-2-3-4-5 accounting for 21.1%-54.9%-19.7%-1.4%-2.8%. There were 103 (42.0%) d-irAEs with grades 1-2-3-4-5 accounting for 23.3%-53.4%-17.4%-5.8%-0%. Of the d-irAEs, 17 (16.5%) occurred >365 days from initiation of ICI. The 3 most common irAE in this patient population included thyroiditis (34%), dermatitis (21%), and pneumonitis (12%). Our data shows a significant survival difference in patients with an irAE compared to those without (p<.01). No significant survival difference was noted between patients who had s-irAE vs d-irAE (p=.069). Conclusions: Our results show that irAEs may be underrecognized and often not formally diagnosed by non-oncology providers. However, median time to diagnosis is short within this context. This may be due to non-oncology providers feeling uncomfortable making the final decision, which emphasizes the importance for oncologists to finalize irAE diagnoses. We did see a positive impact on survival with irAE presence. While oncologists often clinically expect irAEs to surface within the first 6-10 weeks of treatment, our study demonstrates that 42% of irAEs occur after 12 weeks from ICI initiation. There is no difference in survival between s-irAEs vs d-irAEs, and overall grade distribution between these two groups appears similar.

e14605 Background: Increased use of immune checkpoint inhibitors (ICI) has resulted in a rise in immune related adverse events (irAEs). In 2019, pembrolizumab and nivolumab received approval for extended interval (EI) dosing at 400 mg intravenous (IV) every 6 weeks and 480 mg IV every 4 weeks, respectively, compared to the standard interval (SI) dosing of 200 mg IV every 3 weeks and 240 mg IV every 2 weeks, respectively. Since EI dosing has been implemented, clinicians have hypothesized increased dosing may lead to more irAEs. Mixed results have been published to date with discordant results between studies. The aim of this study was to investigate the incidence and grade of irAEs, including multisystem adverse events (ms irAEs) in SI versus EI dosing in a real-world community-based hospital system in the United States of America. Methods: We performed an Institutional Review Board approved retrospective study of all patients 18 years or older who received SI or EI dosing of pembrolizumab or nivolumab from 2015 through 2021. An irAE was considered connected to the specific dosing group if it was observed after the first date of stated dosing and within 90 days after last dose of such dosing. Statistical analysis included descriptive statistics, Wilcoxon signed-rank test, Fisher’s exact test, and Kaplan-Meier survival analysis and was performed in R version 4.2.2 at a significance level of 0.05. Results: Our study included 458 patients who were 99% white, 59% male, and an average age of 67 years. There were 354 (77%) patients in the SI group and 104 (23%) in the EI group. The overall incidence of irAEs was 32% (146 patients), of which 37% (54 patients) presented at some point with ms irAEs. There was no significant association between dosing group and presence of irAEs (p = 0.087), grade groups 1-2 vs > 3 (p = 0.7), or ms irAEs (p = 0.13). The incidence of irAEs was 34% (120 patients) in the SI group with a distribution of grades 1-2-3-4-5 being 39-62-25-5-1, respectively. The incidence of irAEs was 25% (26 patients) in the EI group with a distribution of grades 1-2-3-4-5 being 18-27-11-1-0, respectively. In the SI group there were 41 (34%) patients with ms irAEs compared to 13 (50%) in the EI group. There was a significant association between dosing groups and overall survival (p < 0.001). Conclusions: Our results lend data to suggest there is indeed no statistically significant risk of increased irAEs with EI dosing. However, there may be a clinically significant trend toward increased ms irAEs in EI dosing that needs further investigation with comparisons of comorbid conditions that increase risk of autoimmune reactions. Of note, the OS in EI dosing group was statistically significant but likely heavily confounded due to patient selection bias, this may also be an avenue for future research to be conducted with a randomized clinical trial.

Trial E1609 demonstrated superior overall survival with ipilimumab 3 mg/kg (ipi3) compared to high-dose interferon (HDI) for patients with resected high-risk melanoma. To inform treatment tolerability, we compared health-related quality of life (HRQoL), gastrointestinal (GI), and treatment-specific physical and cognitive/emotional symptoms. We also compared treatment-specific concerns between all arms. We assessed HRQoL using the Functional Assessment of Cancer Therapy-General, physical and cognitive/emotional concerns using the FACT-Biologic Response Modifier subscale, and GI symptoms with the Functional Assessment of Chronic Illness Therapy-Diarrhea subscale pre-treatment and every 3 months. The primary outcome was the difference in HRQoL at 3 months between ipi3/ipi10 vs. HDI. 549 patients (n = 158 ipi3; n = 191 ipi10; n = 200 HDI) were analyzed. 3-month completion was 58.7%. Compared to HDI, ipilimumab patients reported better HRQoL (ipi3 = 87.5 ± 14.6 vs. HDI = 74.7 ± 15.4, p < .001; ipi10 = 84.9 ± 16.5 vs. HDI, p < .001) and fewer physical (ipi3 = 22.3 ± 4.6 vs. HDI = 17.1 ± 5.4, p < .001; ipi10 = 21.8 ± 5.0 vs. HDI p < .001) and cognitive/emotional (ipi3 = 18.6 ± 4.4 vs. HDI = 15.0 ± 5.3, p < .001; ipi10 = 17.7 ± 4.8 vs. HDI p < .001) concerns, but worse GI symptoms (ipi3 = 40.8 ± 5.0 vs. HDI = 42.2 ± 2.9, p = .011; ipi10 = 39.5 ± 7.0 vs. HDI, p < .001). Fewer ipilimumab patients reported worsening treatment-specific concerns (e.g., 52% of ipi3 and 58% of ipi10 reported worsening fatigue vs. 82% HDI, p’s < .001). PROs demonstrated less toxicity of ipi3 compared to HDI and ipi10. Priorities for symptom management among patients receiving ipilimumab include GI toxicities, fatigue, weakness, appetite loss, arthralgia, and depression. Trial Registration: NCT01274338, January 11, 2011 (first posted date) https://clinicaltrials.gov/ct2/show/NCT01274338?term=NCT01274338&draw=2&rank=1 .

Introduction: Increased immune checkpoint inhibitor (ICI) use in various advanced cancer types has led to a parallel rise in immune-related adverse events (irAEs). Despite widespread use, ICI data in older patients remains limited. We investigate irAE prevalence in older patients receiving ICI and whether irAEs and survival are associated.Materials and Methods: Our retrospective study included patients aged >= 65 years with advanced malignancies who had >= 1 dose of ICI from January 2011 through September 2019. We evaluated irAE cases and their respective grades and assessed oncological response by progression-free survival (PFS) and overall survival (OS).Results: Mean age of 210 patients was 75.0 +/- 7.2 years, 58.1% were men, and most were white. IrAE prevalence was 41.4% (n = 87); 9.5% (n = 20) developed multisystem irAE. Most irAEs were grades 1 and 2 (27.6% and 49.4%, respectively), while grades 3 and 4 accounted for 17.2% and 5.8%, respectively. No grade 5 irAE occurred. Compared with patients with no irAEs, those with irAEs had improved OS (HR [hazard ratio], 0.41; 95% CI [confidence interval], 0.282-0.597; p < 0.0001) and PFS (HR, 0.311; 95% CI: 0.213-0.453; p < 0.0001). Improved OS was seen with irAE grades 1 and 2 versus grades 3 and 4 (HR, 0.344; 95% CI: 0.171-0.694; p = 0.0029). Similarly, improved PFS was seen with lower grade irAE (HR, 0.489; 95% CI: 0.247-0.965; p = 0.0391).Discussion: The irAE prevalence in older patients was similar to that in younger patients. To our knowledge, this is one of few studies that confirms a positive association of irAE on both OS and PFS in older patients with cancer, and improved OS and PFS with lower versus higher grade irAE.

e20537 Background: There are currently no clear national guidelines for management of in-situ (stage 0) non-small cell lung cancer (NSCLC). With no prospective clinical trial data, treatment strategies include both surgical resection and definitive radiation therapy (RT). We aimed to investigate survival outcomes in patients with stage 0 NSCLC who underwent surgery or RT. We also aimed to identify any differences in the treatments that the two groups received with respect to rural versus urban setting and racial variation. Methods: The 2016 National Cancer Data Base was reviewed from 2006-2015 for patients registered with a pathological diagnosis of Stage 0 NSCLC, based on the AJCC 7th edition classification for lung cancer. Patients with a prior history of malignancy, secondary malignancy other than lung, and contraindications to surgery were excluded. Univariate comparison and multivariate logistic regression modeling were utilized to identify factors associated with receipt of surgery. Patients were stratified into two groups, surgical resection and RT. Kaplan-Meier estimators and Cox proportional-hazards regression were used to compare overall survival(OS). Propensity score matching was performed using relevant demographic and clinical factors associated with receipt of surgery. All analysis was completed in SAS version 9.4 and p-values less than 0.05 were considered significant. Results: A total of 156 patients were identified with Stage 0 NSCLC who received surgery (n = 104) or RT (n = 52). Surgery was defined as lobectomy or less. Histologic subtypes were squamous cell carcinoma (54%), adenocarcinoma (45%), and bronchioloalveolar carcinoma (1%). Median age was 65 years for the surgical resection cohort and 70 years for the RT cohort. From diagnosis, median time to surgery was 21 days for the surgical resection cohort and 47 days to start of radiation for RT cohort. We did not identify any major differences with respect to rural versus urban setting or racial differences within the surgery and RT cohorts. Patients who underwent surgical resection had a superior 5 year overall survival 65% (CI, 43.49-80.56) when compared to patients who underwent RT 37% (CI, 10.63-65.05), hazard rate 0.403, p = 0.0009, 95% CI. 0.236 – 0.689). Conclusions: Our findings show a significant improved survival with surgical resection compared to RT in patients diagnosed with Stage 0 NSCLC.

9022 Background: Lobectomy is the current standard of care for patients with stage I non-small cell lung cancer (NSCLC). There is a lack of prospective data on the benefit of adjuvant chemotherapy (CT) in patients with negative margins but with high-risk features: lympho-vascular invasion (LVI) or visceral pleural invasion (VPI). We aimed to investigate the benefit of adjuvant CT in patients with pathological stage I NSCLC with high-risk features. Methods: The 2016 National Cancer Database was queried to identify patients with pathological stage I NSCLC (8th edition AJCC staging) diagnosed from 2010-2015 who received lobectomy/pneumonectomy with clear surgical margins. Patients were stratified into high risk (tumor size ≥2 cm with LVI and/or VPI) or low risk group. Multivariate Cox proportional hazards regression and propensity score matched Kaplan-Meier survival analysis were used to compare overall survival between those who received adjuvant CT and those who did not. Results: 34,556 patients were identified with 1114 (3.2%) receiving adjuvant CT. On multivariate Cox regression analysis, high risk tumors (hazard ratio [95% confidence interval] = 1.31 [1.25-1.38]) and lack of adjuvant chemotherapy (1.25 [1.09-1.44]) were associated with worse overall survival (OS). Additionally, male sex, age ≥ 60 years, higher comorbidity burden, lack of insurance, low facility volume, low median income, non-squamous histology were associated with worse OS. After propensity score matching, Kaplan-Meier survival analysis of the high risk subgroup (n = 2923) showed a significant difference in overall survival (OS) between those who received adjuvant CT (n = 1032, 5 year OS, 74.7%; 95% CI, 70.9%-78.0%) and those who did not (n = 1891, 5 year OS, 66.9%; CI, 63.9%-69.6%; p = 0.0002). In patients with no high risk factors for recurrence (n = 384), OS was not significantly different between the patients who received adjuvant CT (n = 78, 5 year OS, 75.8%; CI, 61.3%-85.5%) and those who did not receive adjuvant CT (n = 306, 5 year OS, 77.1%; CI, 70.0%-82.7%; p = 0.3). Conclusions: Our study showed better survival with adjuvant CT in patients with pathological stage I NSCLC who have tumor size greater than 2 cm, LVI and/or VPI.

e24014 Background: Increased use of immune checkpoint inhibitor (ICI) therapy over various cancer types has resulted in a parallel rise in immune-related adverse events (irAEs). There is limited data with regards to understanding irAEs in the elderly population despite its widespread use. We aimed to investigate irAEs in elderly patients receiving checkpoint inhibitor immunotherapy in a community oncology practice setting. Methods: Our retrospective study included patients ≥65 years old treated at a community oncology practice setting from January 1, 2011 through September 30, 2019 who received at least one treatment of a PD-1 or PDL-1 inhibitor (PDI) and/or CTLA-4 checkpoint inhibitor. We evaluated the prevalence of irAEs, determined if age, class of ICI, or oncologic response (clinical and radiographic) was associated with higher grades of irAE. The impact of irAEs on progression-free survival (PFS) and overall survival (OS) was also analyzed. Results: A total of 210 patients were identified, of which 76 developed irAEs. The overall mean age was 75.0 ± 7.2 years. Males accounted for 58% and the overall majority were Caucasian. The most common cancers were lung (56.7%), melanoma (20.0%) and genitourinary (14.8%). The prevalence of irAEs was 36.2% with a distribution of grades 1-2-3-4-5 being 31.6% - 43.4% - 17.1% - 6.6% and 1.3%, respectively. Hazard ratio adjusted for number of cycles for OS was 1.47 (95% CI, 0.98 to 2.19; p = 0.058) and PFS was 1.11 (95% CI, 0.72 to 1.71). Conclusions: To our knowledge, this is one of the few studies that has explored irAEs in the geriatric population. There was no association between ICI-associated higher-grade toxicities and oncologic response in our elderly population. Although there was a trend in OS, we found no statistical differences between elderly patients with irAEs and those without for OS and PFS. Further study is needed to explore the occurrence irAEs in the elderly to improve management of these patients.

More than two-thirds of patients with non–small-cell lung cancer (NSCLC) have locally advanced or metastatic disease at presentation.1 Various targeted agents are approved for patients with a targetable driver mutation. However, most patients lack driver mutation and chemotherapy in the form of platinum doublet used to be the standard of care. The response rate with cytotoxic chemotherapy at best is approximately 30% and median survival is less than a year.2,3 In addition, patients with advanced nonsquamous NSCLC, maintenance pemetrexed has improved survival compared with placebo.

Lung cancer is the leading cause of cancer-related death worldwide. 1In 2012, an estimated 1.8 million new lung cancer cases were diagnosed. 1Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases, and approximately 40% of these patients present with stage III disease. 2 For patients whose disease is deemed unresectable, concurrent chemoradiation (CRT) is the standard of care.A phase II study (SWOG 9010) conducted by Albain et al 3 was the first landmark trial showing the feasibility of the cisplatin/etoposide combination with radiotherapy in patients with locally advanced NSCLC.Concurrent CRT treatment is superior to a sequential approach, but has the disadvantage of increased toxicity. 4p to 10% of patients receiving concurrent CRT will have early treatment-related mortality. 5Despite this intense therapy with curative intent, median survival is approximately 18 to 28 months and only approximately 15% of these patients are alive at 5 years. 4,5Unfortunately, no major advances have been made in this group of patients for many years.The use of a higher dose of radiation does not improve survival and is associated with inferior outcomes.Additionally, no role for targeted therapy with CRT has been proven.Antonia et al 6 recently reported the results of the phase III PACIFIC trial, which evaluated the role of durvalumab (a selective monoclonal antibody against programmed death-ligand 1 [PD-L1]) as consolidation therapy in patients with stage III, locally advanced, unresectable NSCLC that had not progressed after concurrent CRT therapy.The study used a fixed time frame for randomization, and immunotherapy was started without significant delay.A total of 709 patients were randomly assigned in a 2:1 fashion to receive either durvalumab (n=473) or placebo (n=236) every 2 weeks for up to 12 months.The study revealed significant improvement in progression-free survival (PFS) with durvalumab: 16.8 months (95% CI, 13.0-18.1)versus 5.6 months (95% CI, 4.6-7.8) in the placebo arm.The benefit was seen irrespective of sex, smoking status, PD-L1 expression, and tumor histology type.Additionally, the development of new lesions was lower in the durvalumab arm (20.4% vs 32.1%).The brain is a common metastatic site for NSCLC, and has been historically associated with decreased survival and poor quality of life.The rate of new brain lesions in the PACIFIC trial was almost halved with durvalumab (5.5% vs 11.0%).Although the overall survival (OS) data are yet to mature, a PFS benefit of almost a year and a significant decrease in the occurrence of new lesions, including brain lesions, provide reasons to consider durvalumab as a new standard of care.Various platinum-based chemotherapy regimens can be used for concurrent CRT, including cisplatin/etoposide, carboplatin/paclitaxel, cisplatin/vinblastine, and, for nonsquamous pathology, carboplatin or cisplatin with pemetrexed. 7The carboplatin/ paclitaxel regimen is given weekly with radiation therapy, at carboplatin dosed to an area under the curve (AUC) of 2 and paclitaxel dosed at 45 to 50 mg/m 2 , followed by 2 additional cycles of full-dose chemotherapy (carboplatin, AUC=6 and paclitaxel, 200 mg/m 2 ). 8Should treating oncologists therefore omit these 2 additional full-dose chemotherapy cycles when using this regimen?The authors of the PACIFIC trial do not comment on this issue.Also, can these data be extrapolated to the subset of pa-

BACKGROUND/AIM:The role of cytoreductive nephrectomy (CN) for metastatic renal cell cancer (mRCC) is not clearly understood after the approval of targeted therapies, particularly in the elderly population. The aim of this study was to compare survivals between patients who did and did not receive CN.PATIENTS AND METHODS:The SEER-18 database was utilized in order to identify elderly patients with mRCC to compare overall survival (OS) and cancer-specific survival (CSS) between patients who did or did not receive CN between February 2006 and 2012. Kaplan-Meier curve and log rank test were used to compare OS and CSS between these two arms. Cox proportional hazard model was used for multivariate analysis and statistical significance was defined as p≤0.05.RESULTS:There was a significant survival benefit for those who received CN compared to those who did not receive CN (median OS: 18 months vs. 4 months, p<0.001; median CSS: 21 months vs. 5 months, p<0.001).CONCLUSION:CN offered significant survival benefit, even in elderly patients with metastatic renal cell cancer.

10046 Background: The SIPAT is used to assess psychosocial risk in solid organ transplants but data in HSCT is lacking. We examined if pre-HSCT SIPAT scores predict mortality, morbidity, length of stay (LOS) and number of hospitalizations over a 1 year period. Methods: 89 adult HSCT (59% autologous, 38% allogeneic) pts from an academic medical center underwent the SIPAT pre-HSCT. Additional data were obtained on Day 0, and 3-, 6-, and 12-months. Univariable Cox proportional hazards models assessed the instantaneous risk of mortality at any given time after Day 0 as a function of baseline pt characteristics and the SIPAT score. Results: TheSIPAT categorized 28%, 66% and 5.7% respectively of the pts as excellent (E), good (G), and high risk (HR) candidates. One year post HSCT, 76% of E, 72% of G, and 40% of HR candidates were alive. Higher SIPAT scores were a significant predictor of mortality. Compared to E candidates, the HR candidates were 5.94 (95% CI: 1.31-26.81) times more likely to die any time after Day 0 – even after controlling for pts’ comorbidity index ( p = .02). Similarly, compared to G candidates, HR pts were 4.81 (95% CI: 1.33-17.47) times more likely to die even after controlling for pts’ comorbidity index ( p = .01). There was no difference between the G and E candidates on univariable ( p = .75) or multivariable analysis controlling for comorbidity index score ( p = .72). For every 1 point increase in pts’ adherence score, the risk of death was expected to decline by approximately 14% ( HR = 0.86, 95% CI: 0.78 – 0.96; p = .01). SIPAT items that predicted mortality were depression ( p = .02), deceptive behavior ( p < .001) and moderate alcohol abuse ( p < .001). In linear regression analysis, higher SIPAT score was associated with longer LOS ( p = .04) but not infection ( p = .23), GVHD ( p = .40), or number of hospitalizations ( p = .73). Because there were only 18 mortality events, multivariable analyses were limited. Future research will examine the effect of SIPAT on time to death controlling for other pt comorbidities. Conclusions: We found the SIPAT was able to predict mortality and LOS in HSCT pts. This finding if validated in a multi-center manner could be an important tool for HSCT pt selection.

Background: Familial MPNs are uncommon disorders that, like sporadic cases, are characterized by clonal hematopoiesis and presence of somatic mutations, e.g. JAK2, CALR, MPL and occasionally TET2. There is little information, however, about germ-line mutations in these families that may explain the low penetrance hereditary predisposition. Methods: We studied five families with MPNs, each with at least 2 affected members. After obtaining an informed consent, clinical data was obtained from the patients’ electronic medical records. Blood and buccal samples were collected from patients and unaffected relatives. Exome sequencing was performed on the blood DNA samples using Agilent SureSelect Human All Exon V5+UTRs exome capture kit followed by massively parallel sequencing with Illumina HiSeq 2000. Sanger sequencing was then done on both the blood and buccal swab DNA samples to validate selected gene variants and to differentiate the nature of those variants (germ line or somatic). Results: The 5 families participating in this study had the following diagnoses: 1. Mother: polycythemia vera (PV); son: essential thrombocythemia (ET), 2. Mother: primary myelofibrosis (MF); daughter: unclassifiable MPN (UMPN), 3. Father: PV; son: PV, 4. Sister: MF; sister: MF, 5. Two aunts: MF; niece; UMPN. Six patients were positive for JAK2, V617F mutation. Blood and buccal samples were collected from 5 patients and 4 relatives. In all 5 families, the pro-band was younger at the time of diagnosis than his/her affected relatives. The clinical course of the MPNs appeared to be similar to the sporadic form. Exome sequencing revealed TET2 mutations in 2 probands. In addition, novel non-synonymous mutations in several candidate genes, KMT2D , KMT2C , NBEAL1 , NBEAL2, AHNAK2 , RNF213 , were identified in the blood samples from the patients but not their unaffected relatives. These include two novel KMT2D mutations in two unrelated families. These 2 mutations were also found in the matching buccal swab samples, indicating that they are germ line mutations. Discussion: KMT2D and KMT2C mutations have been previously identified as somatic mutations in lymphoid malignancies, including non-Hodgkin’s lymphomas (Morin 2011), and as germ line compound heterozygote mutations in infant MLL and ALL (Valentine 2014). About 32% of diffuse large cell lymphoma and 89% of follicular lymphoma have somatic mutations of KMT2D. NBEAL2 germ line mutations are associated with familial gray platelet syndrome, where some patients have myelofibrosis (Gunay-Aygun 2011). To our knowledge, this is the first report describing germ line mutations in familial MPNs. The possible role of these mutations in predisposition to MPN will be discussed. Studies on additional families with MPNs are planned. Disclosures No relevant conflicts of interest to declare.

The myelodysplastic syndromes (MDS) are stem cell disorders characterized by ineffective hematopoiesis and peripheral cytopenias [1]. Over 10 000 cases per year are diagnosed in the United States [2]. The incidence rises to 20–50/100 000 per year over the age of 60 [3]. The current World Health Organization (WHO) classification (2008) [4,5] includes a new diagnostic category of MDS: refractory cytopenias with unilineage dysplasia (RCUD), defined by 410% morphological dysplasia limited to a single myeloid lineage, 51% peripheral blood blasts, 55% bone marrow blasts, and unior bi-cytopenia (pancytopenia is not allowed). RCUD is further subdivided into refractory anemia (RA), refractory neutropenia (RN), and refractory thrombocytopenia (RT), according to the dominant peripheral cytopenia. While RA with ring sideroblasts (RARS) meets RCUD criteria, it is kept separate given its distinctive morphologic features. RA and RARS represent the majority of cases of MDS with unilineage dysplasia; RN and RT are considered rare, and extreme caution is recommended in making these latter diagnoses [4]. It is postulated that RN and RT exhibit low-risk features similar to RA/RARS. However, there is very limited clinical information reported about these new categories, and none from the United States. We report the incidence, presenting clinical and pathological features, clinical course, and outcomes of patients with RN and RT diagnosed and followed at a single center in the United States. We performed a retrospective review of 293 consecutive patients diagnosed with MDS (1992–2009) at the Minneapolis Veterans Affairs Medical Center (VAMC), with approval from the institutional human subjects committee. Cytopenias were defined as hemoglobin 510.0 g/dL, absolute neutrophil count 51.86 10/L, and platelet count 51006 10/L [6,7]. Diagnostic and follow-up peripheral smears and bone marrow specimens were reviewed by both hematopathologists (A.R. and H.M., blinded to clinical information) to re-confirm the diagnosis. Statistical analysis was performed using GraphPad Prism 5.0 (GraphPad Software Inc., San Diego, CA). Differences between groups were compared using a two-tailed t-test. The probabilities of overall survival (OS) were determined using the Kaplan– Meier method and compared by log-rank (Mantel– Cox) test. Amongst 293 consecutive patients diagnosed with MDS, five (1.7%) with RN and six (2.0%) with RT were identified, and compared with 27 (9.2%) patients diagnosed with RA/RARS during the same period (Supplementary Table S1). In studies of isolated cytopenias (other than anemia) in MDS published prior to the WHO 2008 classification, the incidence of isolated thrombocytopenia was reported to range from 1% [8] to 8.9% [9]. Fenaux et al. [10] reported the incidence of ‘RN/RT’ as 3.2% (eight RN, two RT, amongst 312 patients with MDS). However, since publication of the WHO 2008

Autopsy is the gold standard for establishing the cause of death. We present results of the largest retrospective review of complete autopsies of subjects after hematopoietic stem cell transplantation to better define the role of the autopsy in discovering a missed diagnosis. We reviewed the medical chart and autopsy records of 111 patients who had undergone hematopoietic stem cell transplantation from July 1986 to June 2003 from a single center. We compared the cause of death as charted by the clinical team with data obtained from postmortem chart review and autopsy reports. Of 29 (26%) cases when the premortem and postmortem major diagnoses did not agree, only 4 (4%) autopsy records provided data that might have led to the initiation of new treatments, and none of these diagnoses would be missed today with more sensitive and specific diagnostics and improved supportive care. Although autopsies after transplantation can be important educational, research, and epidemiologic tools and provide an emotional benefit to patient’s families, in our series they rarely provided missed diagnoses that would alter the management of subsequent patients. Improvements in noninvasive tests for relapse or occult infections may further erode the role of autopsies in discovering missed diagnoses. © 2007 American Society for Blood and Marrow Transplantation

Autopsy is the gold standard for establishing the cause of death. We present results of the largest retrospective review of complete autopsies of subjects after hematopoietic stem cell transplantation to better define the role of the autopsy in discovering a missed diagnosis. We reviewed the medical chart and autopsy records of 111 patients who had undergone hematopoietic stem cell transplantation from July 1986 to June 2003 from a single center. We compared the cause of death as charted by the clinical team with data obtained from postmortem chart review and autopsy reports. Of 29 (26%) cases when the premortem and postmortem major diagnoses did not agree, only 4 (4%) autopsy records provided data that might have led to the initiation of new treatments, and none of these diagnoses would be missed today with more sensitive and specific diagnostics and improved supportive care. Although autopsies after transplantation can be important educational, research, and epidemiologic tools and provide an emotional benefit to patient's families, in our series they rarely provided missed diagnoses that would alter the management of subsequent patients. Improvements in noninvasive tests for relapse or occult infections may further erode the role of autopsies in discovering missed diagnoses.