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733 Background: VHL disease is a rare hereditary condition that causes abnormal tumor growth in multiple organs, including renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas (Hb), pancreatic neuroendocrine tumors (pNET), and other tumors. Repeated surgeries are often required due to ongoing tumor recurrences and can lead to complications such as chronic kidney disease, pancreatic insufficiency, and neurological deficit. Belzutifan is a hypoxia-inducible factor inhibitor approved in the US for the treatment of VHL-associated RCC, CNS Hb, or pNET not requiring immediate surgery. This study aimed to quantify the annual rate and costs of VHL-related surgeries and surgical complications before and after belzutifan initiation. Methods: Surgeries were observed during the periods before and after belzutifan initiation in the single-arm phase 2 LITESPARK-004 trial (NCT03401788) among adults with VHL-RCC. Rates of RCC surgeries were obtained by fitting exponential survival models to: time from treatment initiation to the next renal surgery; and time (looking backward) from treatment initiation to the most recent renal surgery before treatment. Rates of surgeries related to other VHL manifestations were calculated as number of surgeries divided by person-years at risk, using all available post-treatment follow up (151 person-years; median [range] per patient: 29.2 [4.2-37.5] months) and equivalent person-years in the pre-treatment period. Complication risks per surgery and unit costs of surgeries and complications were obtained from a retrospective study on VHL within the Optum Clinformatics Data Mart (2000-2020). Annual per-patient costs of surgeries and complications were estimated in 2020 US dollars over the pre- and post-treatment periods from a US third-party payer perspective. Results: Among trial participants (N=61), the rate of RCC surgeries (surgeries/person-year) decreased 87% (0.108 to 0.014) after belzutifan initiation. The rate of other surgeries decreased 98% (0.265 to 0.007), with CNS Hb surgeries decreasing from 0.185 to 0.007, pNET surgeries from 0.013 to 0, adrenal lesion surgeries from 0.007 to 0, and retinal Hb surgeries from 0.060 to 0. Belzutifan was accordingly estimated to reduce per-patient average annual costs of surgeries and complications from $57,259 to $2,536. Conclusions: Healthcare costs of surgeries and surgical complications are substantial among patients with VHL-RCC. In a trial-based cost-consequence analysis, belzutifan was estimated to decrease annual surgery and complication costs by 96%, based on observed reductions in VHL-related surgeries. [Table: see text]

Electrochemical discharge machining (ECDM) is an emerging micromachining method to drill advanced non-conductive materials such as Hexagonal boron nitride (hBN). Physical contact of micro tools with work material could cause machining inaccuracies, excessive tool wear, and even tool breakage. In this study, a control system based on monitoring the force generated by the ECDM gas film has been developed to achieve non-contact machining of ECDM by dynamically adjusting the tool feed rate. The accuracy of the control system was verified by accelerometer and Fast Fourier Transformation (FFT) data. In the modules, it was found that a non-contact machining process requires the FFT amplitude to be lower than 42 V for a 1200 rpm tool rotation. The experimental results show consistent micro-holes with an average diameter of 650 µm and less than 20 µm error in the overcut achieved using this control system.

The objective of this study was to describe real-world health-related quality of life (HRQoL) and treatment satisfaction of ibrutinib-treated patients with CLL compared to a reference group. This study was completed in two parts. The first portion (Norming Study) was a US online survey conducted to serve as a reference population. The Norming Study included a total of 139 patients with CLL, excluding those treated with ibrutinib: 64 were treatment naive (Tx naive), 36 were 1st line (1L), and 38 were in or had completed ≥2 lines (2L+) patients with CLL. The second portion (CLL Ibrutinib Study) included 1L and 2L+ ibrutinib patients with CLL treated for ≥6 months in which 118 patients (1L n = 88 and 2L+ n = 30) completed the study. Respondents completed demographic and clinical information and the following HRQoL surveys: (Short Form-12v2® Health Survey [SF-12v2], Functional Assessment of Cancer Therapy-General [FACT-G], FACT-Leukemia [FACT-Leu] Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue, and Cancer Therapy Satisfaction Questionnaire [CTSQ]). Higher scores indicate better HRQoL/treatment satisfaction. Differences in effect sizes between the two samples at the group level were calculated using Hedges’ g. Medium to large positive effects were seen in the CLL Ibrutinib group on several measures compared to the Reference Study groups. The FACT-G total score was 89.2±11.1 for CLL Ibrutinib Study patients compared to 75.8±22.6 CLL Norming Tx naïve patients, 61.3±21.8 in 1L, and 61.7±20.7 in 2L+. Similar trends were seen with FACT-Leu total score and FACIT-Fatigue. CLL Ibrutinib Study patients scored higher on all CTSQ domain scores compared to the CLL Norming patients treated with other CLL therapies. We found that Ibrutinib-treatment had better HRQoL and treatment satisfaction compared to patients receiving other therapies, irrespective of line of therapy.

4543 Background: Prior research shows that post-nephrectomy recurrence is correlated with significantly increased mortality in patients (pts) with intermediate-high (int-high) risk and high risk RCC. However, no study has quantified the incremental OS associated with increased time to recurrence (ToR). Additionally, limited evidence is presented on the variation of recurrence rate and OS by stage of RCC. Methods: The SEER-Medicare database (2007–2016) was used in this retrospective observational study. Post-nephrectomy pts with newly diagnosed, int-high risk (pT2 N0 high grade, pT3 N0 any grade) or high-risk (pT4 N0 any grade, pT any N1 any grade) RCC were identified and stratified based on tumor stage and grade. Grade was defined based on Furhman grading system and was reported in SEER Registry. Post-nephrectomy recurrence free rates and OS by disease stage were described using Kaplan-Meier analyses. OS from nephrectomy in pts with recurrence vs pts without recurrence was compared by disease stage. Multivariable regression analysis was used to quantify the incremental OS associated with increased ToR post-nephrectomy in all pts with recurrence. Results: 643 pts met the inclusion criteria (269 with vs 374 without recurrence; median follow-up: 23 months). The mean age was 75.5 years (yrs), 61% male, and 86% white. Results presented in the table showed wide variance in 5-yr recurrence-free rate in int-high risk group (28%-63%) and indicated substantial risk of disease recurrence in all subgroups of int-high risk pts. Among those with T3 Grade 1-2, T3 Grade 3, and T3 Grade 4 disease, pts with recurrence had significantly higher risk of death than those without (all ps

4539 Background: VHL disease is an inherited condition associated with tumors in multiple organs; RCC may affect up to 70% of patients with VHL. Patients often need many tumor reduction procedures (TRP) to manage renal neoplasms. This study evaluated TRP treatment patterns, costs, and complications among patients with VHL-RCC. Methods: Using an algorithm based on VHL manifestations, patients with VHL were identified from the Optum Clinformatics claims database. Patients were then selected with a prior RCC diagnosis. Minimum continuous enrollment of 12 months before and 3 months after first observed RCC diagnosis was required. TRPs for RCC included nephrectomy, renal ablation, and cryotherapy. Time to first TRP from initial observed RCC diagnosis was estimated using Kaplan-Meier analysis. Mean hospitalization costs per TRP type were estimated. Costs associated with TRP complications were estimated via linear regression; the explanatory variable was the presence of a given complication. Short-term complications were evaluated for 4 weeks post-TRP; long-term ones were evaluated over 6 months. Renal function was evaluated using chronic kidney disease (CKD) stages before and after TRPs, using diagnosis codes and eGFR lab values. Results: 160 patients with VHL-RCC were identified; mean follow-up time was 34.1 months. 115 (71.8%) patients incurred ≥1 RCC TRP over their study period. 68.4% had a TRP in the first year after RCC diagnosis and 76.5% had TRPs by year 5. Of the 125 observed TRPs, 97 (77.6%) were nephrectomies and 28 (22.4%) were ablation/cryotherapy. The mean costs for nephrectomy were nominally higher vs. ablation/cryotherapy ($29,313 vs. $18,290). The most common short-term complications were respiratory related (20.8%) and vascular injury/anemia (13.6%). The most common long-term complications were CKD stage 1-5 (24.0%) and end-stage renal disease (chronic dialysis dependence) (4.0%). The most expensive complications were related to impaired renal function: acute renal failure ($21,013 over 4 weeks), CKD ($26,032 over 6 months) and end stage renal disease ($65,338 over 6 months). At baseline, the proportion of patients with a diagnosis of CKD ≥ stage 3 was similar between patients who had TRPs (n = 115) and those who did not have TRPs (n = 45): 24.3% and 24.4%, respectively. After the first TRP, the proportion of patients with CKD ≥ stage 3 increased from 24.3% to 41.7%. Conclusions: Patients with VHL-RCC incur a significant clinical and economic burden related to TRPs for managing their renal tumors. This is in addition to the burden that VHL-RCC patients incur from the management of other VHL tumors. This study underscores the need for novel effective therapies to prevent or delay the recurrence of VHL-related renal neoplasms to mitigate the burden of morbidity and long-term medical management related to VHL.

e16526 Background: Real world evidence (RWE) on patient outcomes among early-stage non-metastatic renal cell carcinoma (RCC) patients (pts) of different risk groups are limited. This RWE study evaluated disease free survival (DFS) and overall survival (OS) patterns and risk of OS among pts with non-metastatic RCC in the US. Methods: This retrospective analysis identified pts, age ≥18 years, with non-metastatic RCC diagnosis between 01/01/2012-12/31/2015, and surgical treatment for RCC prior to metastatic diagnosis. Pts were identified from the ConcertAI Oncology Dataset which draws electronic medical records from 100 community oncology clinics in the US and followed until 08/19/2021. Pts were stratified into intermediate (int)-high (pT2N0 high grade, pT3N0) or high risk (pT4N0, pTanyN1) RCC. Time to event outcomes (DFS, OS) were examined using Kaplan-Meier methods, and association of recurrence and 5yr OS was examined using Cox proportional hazard model, controlling for baseline and clinical characteristics. DFS was defined as time from initial nephrectomy to first recurrence or death, whichever occurred first. OS was defined as time from initial nephrectomy to death. Results: The study included 274 pts (87% int-high risk, N = 239; 13% high risk, N = 35). Overall, pts were 63.5 yrs (median age), 66% male, 78% White, and 73% had clear cell RCC. Median follow-up was 49.5 months (mths). 54% int-high and 69% high risk pts had recurrence. As seen in the table, median DFS ranged from 14.6-64.8 mths and 5yr DFS rates ranged from 10-61% across risk groups. Median OS was 83.4 mths for int-high and 78.4 mths for high risk pts; 5yr OS rate was 69% for int-high and 58% for high risk. Compared to patients without recurrence, pts with recurrence had shorter median OS (93.8 vs 69.6 mths) and lower 5yr OS rate (85% vs 57%). In pts with recurrence, 5yr OS rate was similar between int-high and high risk groups (58% and 57%). Pts with recurrence were 2.4 times (HR = 2.4; 95% CI = 1.5, 3.9) more likely to die 5 yrs post initial nephrectomy compared to pts without recurrence. Conclusions: This study confirms findings from our previous research with SEER data that pts with recurrence had an increased risk of death, compared to pts without. The DFS and OS rates observed in this RWE study are supportive of DFS and OS rates observed in the placebo arm of the KEYNOTE-564 trial. Additionally, poor DFS rates were observed within subgroups of int-high risk pts. The study results indicate the high real-world unmet need in post-nephrectomy int-high or high risk localized RCC pts, highlight the need for effective adjuvant treatments, and inform the design of future interventional trials in non-metastatic RCC pts.[Table: see text]

305 Background: VHL disease is an inherited condition characterized by the formation of benign and malignant tumors in multiple organs, and RCC affects up to 40-70% of patients with VHL disease. However, real-world evidence on HRU and direct healthcare costs related to VHL-RCC is lacking. This study sought to address the gap in the literature by evaluating HRU and healthcare costs associated with the disease. Methods: Patients with VHL disease were identified from the Optum Clinformatics claims data using an algorithm based on combinations of manifestations of the disease. Among the patients identified, those with at least 1 diagnosis of RCC were further selected. The index date was defined as the date of first observed RCC diagnosis in the data, and the study period extends up to 5 years after index date or the end of continuous enrollment, whichever was earlier. A minimum continuous enrollment of 12 months prior to and 3 months after the index date was required. All-cause and RCC-related HRU and healthcare costs were evaluated among eligible patients with VHL-RCC. HRU was expressed as events per person-month and cost was expressed as average monthly cost. HRU and healthcare costs related to other VHL disease-related tumors were also assessed, including central nervous system (CNS) hemangioblastomas (Hb), retinal Hb, and pancreatic neuroendocrine tumors (pNETs). Results: 160 patients with VHL-RCC were included in the analyses. Mean age of the patients was 51.5 years and 89 (56%) were male. During the study period, patients with VHL-RCC incurred 0.10 hospitalizations (0.52 inpatient days), 1.49 outpatient visits, 0.09 emergency department (ED) visits, and 0.17 other medical visits per person-month on average. This translated to a monthly all-cause healthcare cost of $4,276, which included $2,222 inpatient, $1,318 outpatient, $188 ED, $63 other medical visits, and $485 pharmacy costs. $1,627 out of the all-cause cost per month was RCC-related, which was mainly driven by inpatient costs for RCC ($1,184/month). There were also notable costs associated with other tumor types: $2,159/month for CNS Hb, $601/month for retinal Hb, and $3,306/month for pNETs on average. Among patients with VHL-RCC who received surgical procedures for different tumors, the average hospitalization or outpatient visit costs were $28,356 for nephrectomies, $70,515 for CNS Hb surgeries, $2,887 for laser therapy of retinal Hb, and $81,825 for pNET surgeries. Conclusions: VHL-RCC is associated with significant HRU and healthcare costs due to the needs of managing RCC as well as tumors in other organs caused by VHL disease. This highlights the multi-disciplinary nature of VHL disease and the need for novel effective therapies to prevent or delay the recurrence of VHL-related tumors in order to mitigate the economic burden related to the disease.