Background and Aims: Acute cellular rejection (ACR) is a frequent complication after liver transplantation. By reducing ischemia and graft damage, dynamic preservation techniques may diminish ACR. We performed a systematic review to assess the effect of currently tested organ perfusion (OP) approaches versus static cold storage (SCS) on post-transplant ACR-rates. Approach and Results: A systematic search of Medline, Embase, Cochrane Library, and Web of Science was conducted. Studies reporting ACR-rates between OP and SCS and comprising at least 10 liver transplants performed with either hypothermic oxygenated perfusion (HOPE), normothermic machine perfusion, or normothermic regional perfusion were included. Studies with mixed perfusion approaches were excluded. Eight studies were identified (226 patients in OP and 330 in SCS). Six studies were on HOPE, one on normothermic machine perfusion, and one on normothermic regional perfusion. At meta-analysis, OP was associated with a reduction in ACR compared with SCS [OR: 0.55 (95% CI, 0.33–0.91), p=0.02]. This effect remained significant when considering HOPE alone [OR: 0.54 (95% CI, 0.29–1), p=0.05], in a subgroup analysis of studies including only grafts from donation after cardiac death [OR: 0.43 (0.20–0.91) p=0.03], and in HOPE studies with only donation after cardiac death grafts [OR: 0.37 (0.14–1), p=0.05]. Conclusions: Dynamic OP techniques are associated with a reduction in ACR after liver transplantation compared with SCS. PROSPERO registration: CRD42022348356.
420 Background: The determination of progressive disease (PD) on sunitinib in mRCC by conventional tumor size criteria is often complex. Frequently, radiology reports cite disease progression that does not meet RECIST criteria or does not adequately describe index lesions. Characterization of the frequency and magnitude of this phenomenon has not been previously reported. Methods: The medical records of a subset of mRCC patients treated at The Cleveland Clinic who had received sunitinib for > 12 months were retrospectively reviewed. All Radiology reports from post-baseline scans were reviewed for the presence of text in the body or conclusion of the report consistent with disease progression (specifically the terms ‘progressive’, ‘new’ and/or ‘interval enlargement/worsening’). The date of the report first containing one or more of these terms was recorded, as was the date of RECIST-defined PD determined by the treating Oncologist. Results: Twenty patients were identified in an initial review. Patient characteristics included: 85% male, 100% clear cell histology, 90% prior nephrectomy and 80% with prior systemic therapy. Thirteen patients (65%) had a radiology report citing a progressive disease term prior to treating physician-determined RECIST-defined PD. The median time from first radiology report citing a progressive disease term until RECIST PD per Oncologist measurements was 2.9 months (range, 0 to 12.8 months). Conclusions: There is significant discrepancy between the first mention of disease progression by a Radiology report and when a treating Oncologist measures disease progression per RECIST criteria. This discrepancy could impact patient care by influencing drug discontinuation. These data emphasize the importance of multidisciplinary scan review and tumor measurements by both radiologists and treating physicians. Analysis is ongoing in additional patients.
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2081 Background: Patients (pts) with brain metastases (BM) have a poor prognosis and limited treatment options. Approximately 40-50% of pts with NSCLC will develop BM during the course of their disease. A better understanding of the pathobiology of BM and the development of targeted agents hold promise for improved prophylaxis and therapy of BM which could have significant impact on disease progression and pt's survival. Vascular Endothelial Growth Factor has been implicated in setting up a metastatic niche allowing cells to seed and grow in the brain parenchyma. Inhibition of this signaling has been studied and shown to be effective in reducing BM in animal models. Methods: The objective of this retrospective study was to determine whether bevacizumab decreases the incidence and or the recurrence of BM in pts with NSCLC. We retrospectively identified NSCLC pts with and without BM treated with bevacizumab. The primary endpoint was the proportion of patients who developed BM on or after bevacizumab therapy. Secondary endpoints were rate of local or regional recurrence after stereotactic radiosurgery (SRS). Occurrence of BM was evaluated by retrospectively reviewing MRI and or CT scans. Results: A total of 30 pts with stage IV non-squamous NSCLC who had no BM at diagnosis treated with bevacizumab (Non-BM group, NBMG) and 85 pts with non-squamous NSCLC who had BM and underwent SRS (BM group, BMG) were studied (46%M; median age 60 years (range 32-84). In the NBMG, 28% of pts developed BM. Median time to development of BM was 10.5 months. In the BMG, 4 pts were treated with bevacizumab following SRS. Of these 4 pts, 3 pts (75%) had no recurrence while 1 pt (25%) developed local then regional recurrence at 7 and 9 months, respectively. Of the remaining 81 pts who underwent SRS but never received bevacizumab, 27% of pts had local recurrence and 41% had regional recurrence at median time of 4 and 4.5 months, respectively. Conclusions: Bevacizumab may have a role in the treatment of NSCLC in regards to development and recurrence of brain metastases. These results support the need for further prospective investigation in a larger patient population with matched controls.
TPS4684 Background: Sunitinib is a standard of care initial treatment in mRCC. One challenge is balancing the acute and chronic toxicity of therapy with clinical benefit. Pre-clinical and retrospective clinical data support the concept that treatment breaks are feasible and not associated with a reduction in efficacy of sunitinib. It is hypothesized that an intermittent dosing regimen of sunitinib in mRCC pts is feasible, and may lead to prolonged duration of disease control with improved tolerance. Methods: Eligibility criteria include treatment-naïve clear cell mRCC, measurable disease, and adequate organ function. Pts will be treated for 4 cycles of sunitinib (50 mg 4/2) in the absence of unacceptable toxicity or RECIST-defined progression. Pts with ≥ 10% reduction in tumor burden per RECIST following 4 cycles will have sunitinib held, with re-staging CT scans approximately every 10 weeks thereafter to assess tumor burden. Sunitinib will be re-initiated in those patients with an increase in tumor burden of 10% or greater (per RECIST) compared to the scan obtained just prior to holding sunitinib. Pts who have RECIST tumor burden reduction of 10% or more compared to scans at the start of the most recent treatment period will again have sunitinib held. This intermittent sunitinib dosing will continue until RECIST-defined disease progression while on sunitinib. Patients not initially achieving at least a 10% reduction in tumor burden will continue sunitinib. The primary objective is the feasibility of intermittent sunitinib, defined as the proportion of patients eligible for and who undergo intermittent therapy. The alternative hypothesis is a feasibility rate of > 80% vs. the null hypothesis of < 50%. Thirty pts provides 80% power based on a two-sided exact test with a .05 type I error. Secondary endpoints include PFS and toxicity. Twenty five of planned 30 patients have been enrolled.
e13030 Background: In patients (pts) with non-small cell lung cancer (NSCLC), it is unknown whether pts with bone metastases are predisposed to the development of brain metastases. The impact of bevacizumab (Bev) on the development of bone and brain metastases is not fully characterized. Methods: Retrospective review of pts with stage IV NSCLC without brain metastasis at diagnosis was undertaken. The primary endpoint was to determine whether the development of bone metastases is predictive of the development of brain metastases. Secondary endpoints involved the proportion of pts who developed brain and/or bone metastases while being treated with Bev. Data were analyzed using competing risks methods. Results: A total of 175 pts (52% males, median (range) age: 60 y (35-80)) were studied. Of whom 79% received Bev and 21% did not receive Bev as part of their treatment. Overall 34% of pts had bone metastases at the start of therapy. Pts with pre-existing bone metastases tended to develop new bone disease more frequently than pts who did not initially have bone metastases (39% vs. 19%, p =. 01). The incidence of the development of brain metastases among pts who had pre-existing bone metastases was 17% vs.16 % in pts without pre-existing bone metastases. However, the incidence of brain metastases among pts with pre-existing bone disease who developed new bone metastases was 33% vs. 6% in pts who did not develop new bone disease but had pre-existing bone metastases. Adjusting for initial bone disease, development of new bone metastases was associated with a shorter brain metastases-free interval HR 5.06 (2.03-12.65; p = 0.005). In a subgroup analysis based on Bev exposure, the likelihood of developing brain and bone metastases within 2 years of starting Bev was estimated to be 25% and 27%, respectively, while the likelihood of developing brain and bone metastases without Bev treatment was 33% and 43 %, respectively. Conclusions: In pts with NSCLC, the development of new bone metastases may be indicative of the subsequent development of brain metastases. Additionally, Bev therapy may have an effect on the development of both bone and brain metastases. A prospective investigation may be warranted.
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