Adrenocortical carcinoma (ACC) is a rare tumor with a poor prognosis. Identification of clinicopathological features and molecular prognostic markers is important for the treatment of ACC. The aim of this study was to evaluate the clinical and histopathological features of ACC for prognostic prediction.This retrospective cohort study included 86 patients pathologically confirmed with ACC in a single center. Ki-67 index was evaluated by immunohistochemical staining of paraffin-embedded samples.The median age of the 86 (46 male and 40 female) patients with ACC was 49 years old (range 21-78), and the mean primary tumor size was 12.2 ± 5.2 cm. ACCs were incidentally found in 29 patients (34%). Three patients (3%) had bilateral ACC, and 59 patients (69%) had distant metastasis (37 synchronous and 22 metachronous). Twenty-four patients (28%) had symptoms from hormone excess or mass effects, and 25 patients (29%) had nonspecific symptoms. The 5-year survival rate for ACC was 28%. Sixty patients underwent surgical treatment, including 37 patients with an R0 resection. Tumor size, Ki-67 index, stage, and resection status were independently associated with overall survival by multivariate analysis. In patients with R0 resection, recurrence was significantly associated with larger tumor size and functional tumor.Tumor size, Ki-67 index, stage, and resection status are important prognostic indicators of survival in ACC patients.
Von Hippel-Lindau (VHL) disease is an autosomal dominant disease that produces a variety of tumors and cysts in the central nervous system and visceral organs, including renal cell carcinoma (RCC). RCC in patients with VHL disease does not frequently metastasize, therefore, the response to treatment and prognosis of metastatic RCC developed in patients with VHL disease has not been reported. Sunitinib is an oral, multitargeted receptor tyrosine kinase inhibitor with antiangiogenic and antitumor activity. Here, we report on four patients with metastatic RCC in VHL disease who received sunitinib and achieved partial responses that have lasted for a prolonged period of time.
The optimum method of donor natural killer cell infusion (DNKI) after allogeneic hematopoietic cell transplantation (HCT) remains unclear. Fifty-one patients (age range, 19 years to 67 years) with refractory acute leukemia underwent HLA-haploidentical HCT and underwent DNKI on days 6, 9, 13, and 20 of HCT. Median DNKI doses were .5, .5, 1.0, and 2.0 × 108/kg cells, respectively. During DNKI, 33 of the 45 evaluated patients (73%) developed fever (>38.3°C) along with weight gain (median, 13%; range, 2% to 31%) and/or hyperbilirubinemia (median, 6.2 mg/dL; range, 1.0 mg/dL to 35.1 mg/dL); the toxicity was reversible in 90% of patients. After transplantation, we observed cumulative incidences of neutrophil engraftment (≥500/µL), grade 2 to 4 acute graft-versus-host disease (GVHD), chronic GVHD, and nonrelapse mortality of 84%, 28%, 30%, and 16%, respectively. The leukemia complete remission rate was 57% at 1 month after HCT and 3-year cumulative incidence of leukemia progression was 75%. When analyzed together with our historical cohort of 40 patients with refractory acute leukemia who underwent haploidentical HCT and DNKI on days 14 and 21 only, higher expression of NKp30 (>90%) on donor NK cells was an independent predictor of higher complete remission (hazard ratio, 5.59) and less leukemia progression (hazard ratio, .57). Additional DNKI on days 6 and 9 was not associated with less leukemia progression (75% versus 55%).
Supplementary Data from Putative Biomarkers of Clinical Benefit With Pembrolizumab in Advanced Urothelial Cancer: Results from the KEYNOTE-045 and KEYNOTE-052 Landmark Trials
673 Background: Across the world, treatment of patients with mRCC is heterogeneous with different access to treatment sequences and number of lines of therapy (LOTs) employed. For instance, patients receiving first line (1L) nivolumab+ipilimumab (NIVO+IPI) may be offered second-line (2L) and third line (3L) vascular endothelial growth factor receptor targeted kinase inhibitor (VEGFR-TKI), whereas patients receiving 1L pembrolizumab or avelumab in combination with axitinib (IO+AXI) may only receive one subsequent VEGFR-TKI in 2L. We aimed to examine whether these different treatment strategies impact overall survival (OS). Methods: Adult mRCC patients who received at least three LOTs starting with 1L NIVO+IPI or at least two LOTs starting with 1L IO+AXI from the International Metastatic RCC Database Consortium (IMDC) centers were included. Kaplan-Meier analyses were used to estimate median OS (time from 1L to death). Results were stratified by 1L IMDC prognostic risk. Results: Among 128 patients who received at least three LOTs starting with 1L NIVO+IPI (median age 61 years, 77% White, 77% male, 37% from the US), 14% had favorable, 61% had intermediate, and 26% had poor IMDC risk. The most common 2L treatments following 1L NIVO+IPI were sunitinib (38%), cabozantinib (27%), and pazopanib (20%). Among 104 patients who received at least two LOTs starting with 1L IO+AXI (median age 62 years, 75% White, 67% male, 38% from the US), 28% had favorable, 48% had intermediate, and 25% had poor IMDC risk. The most common 2L treatments following 1L IO+AXI were cabozantinib (57%) and sunitinib (10%). Median OS are presented in the table, which suggested no difference in survival for patients who received at least two LOTs starting with 1L IO+AXI compared to patients who received at least three LOTs starting with 1L NIVO+IPI. Conclusions: Treatment for patients with mRCC varies depending on the 1L regimen chosen and by country. Our results demonstrate that, even with potential guaranteed time bias and IMDC imbalances, there is no statistically significant difference in OS for patients who received at least three LOTs starting with 1L NIVO+IPI and patients who received at least two LOTs starting with 1L IO+AXI, suggesting that selecting effective treatments in 1L resulting in fewer LOTs may have similar clinical outcomes as multiple LOTs. [Table: see text]
e15578 Background: Third line targeted therapy efficacy in mRCC is not well characterized and is not reimbursed in many jurisdictions worldwide. Methods: The IMDC consists of consecutive patient series from 25 international cancer centers. It was queried for specific sequences of targeted therapy and third-line therapy. Kaplan Meier estimates were used for survival and proportional hazards regression used to adjust hazard ratios for confounders. Results: 4,450 patients were treated with first-line targeted therapy, of which 2,112 (48%) had second-line therapy and 920 (21%) had third-line targeted therapy. The most common third line therapies were everolimus 26%, sorafenib 13%, sunitinib 13%, temsirolimus 11%, pazopanib 11%, and axitinib 6%. IMDC prognostic groups (Heng et al JCO 2009) and their associated survivals (both determined from third line therapy initiation) were 6% favorable risk (OS 20.1 (14.7-32.6), PFS 6.3 (4.4-12.0)), 67% intermediate risk (OS 15.0 (12.2-16.9), PFS 3.6 (3.2-4.1)) and 27% poor risk (OS 5.5 (4.5-6.5), PFS 2.5 (1.8-3.0)). Overall response rate for third-line therapy was 10.4% and 50.4% had stable disease in those patients that were evaluable (n=516). Median PFS was 3.4 months (95%CI 3.2-3.7) and median OS from third line therapy initiation was 12.4 months (95%CI 11.1-13.4). Table illustrates PFS and OS for each therapy from time of third-line therapy initiation. On multivariable analysis adjusting for IMDC criteria, the hazard ratios for death between the different 3rd line therapies were not statistically significant. Conclusions: Third line targeted therapy has demonstrated activity, is prevalent in use, and should be offered to clinically eligible patients. One agent does not appear to be superior to another in this series. Further studies are required to determine appropriate sequencing. 3rd line therapy PFS (months 95%CI) OS (months 95%CI) Axitinib 4.4 (2.8-5.1) 15.5 (9.4-20.6) Everolimus 3.4 (2.9-3.9) 12.1 (10.1-14.1) Pazopanib 3.5 (2.7-5.0) 13.8 (11.0-19.5) Sorafenib 3.5 (2.9-4.1) 12.5 (10.9-17.1) Sunitinib 4.1 (3.0-5.4) 10.7 (8.0-14.7) Temsirolimus 3.2 (2.5-3.7) 9.9 (7.2-12.5)
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