scholarly journals ASO Visual Abstract: Does the Volume-Outcome Association in Pancreas Cancer Justify Regionalization of Care? A Review of Current Controversies

Author(s):  
Alexandra W. Acher ◽  
Sharon M. Weber ◽  
Timothy M. Pawlik
2020 ◽  
Vol 14 (9) ◽  
Author(s):  
Marian S. Wettstein ◽  
Song Pham ◽  
Syed R. Qadri ◽  
Kathy Li ◽  
Christian D. Fankhauser ◽  
...  

Introduction: Prior research demonstrated an association between surgical case volume and survival in muscle-invasive bladder cancer (BC). This relationship, however, has not been investigated in the setting of T1 BC so far. Therefore, we investigated whether a higher surgical case volume of T1 BC translates into improved survival outcomes. Methods: Province-wide pathology reports (January 2002 to December 2015) were linked with health administrative data to identify patients diagnosed with T1 BC. For each patient, we determined the T1 case volume of the involved surgeon by benchmarking (percentile) her/him against his/her colleagues during a lookback period of one year. The volume-outcome (overall survival) relationship was then investigated by Cox proportional hazards regression (unadjusted and adjusted for a wide range of assumed confounders) that incorporated volume in three different ways (80th percentile and higher vs. below, median and higher vs. below, continuous [quintiles]). Effect sizes were presented as hazard ratios (95% confidence interval). Results: We identified 7426 patients who were diagnosed with T1 BC and followed for 4.8 years. A third of all patients (n=1895, 25.5%) received surgery by a high-volume surgeon (80th percentile and higher). Higher T1 case volume was associated with improved survival both in unadjusted (80th percentile: 0.93 [0.86–0.99]; median: 0.93 [0.87–0.99]; continuous: 0.97 [0.94–0.99]) and adjusted analysis (80th percentile: 0.94 [0.88–1.01]; median: 0.93 [0.87–0.99]; continuous: 0.97 [0.95–0.99]). Conclusions: This province-wide cohort study could demonstrate a volume-outcome relationship in T1 BC and raises questions regarding the regionalization of care in high-risk non-muscle-invasive BC. The generalizability of our findings, however, is limited by the fact that the performance of the initial resection by a high-volume surgeon does not necessarily translate into downstream care by the same surgeon.


Author(s):  
Cara Kenney ◽  
Tricia Kunst ◽  
Santhana Webb ◽  
Devisser Christina ◽  
Christy Arrowood ◽  
...  

SummaryBackground Preclinical evidence has suggested that a subset of pancreatic cancers with the G12R mutational isoform of the KRAS oncogene is more sensitive to MAPK pathway blockade than pancreatic tumors with other KRAS isoforms. We conducted a biomarker-driven trial of selumetinib (KOSELUGO™; ARRY-142886), an orally active, allosteric mitogen-activated protein kinase 1 and 2 (MEK1/2) inhibitor, in pancreas cancer patients with somatic KRASG12R mutations. Methods In this two-stage, phase II study (NCT03040986) patients with advanced pancreas cancer harboring somatic KRASG12R variants who had received at least one standard-of-care systemic therapy regimen received 75 mg selumetinib orally twice a day until disease progression or unacceptable toxicity occurred. The primary outcome of the study was best objective response (BOR). Results From August 2017 to February 2018 a total of 8 patients with confirmed somatic KRASG12R mutations and a median age of 61.5 years were treated with selumetinib. Seven out of eight (87.5%) had received two or more lines of prior systemic chemotherapy. After a median follow-up period of 8.5 months (range 2 to 20), three patients had stable disease for more than 6 months while receiving selumetinib. No patients achieved an objective partial response. Median progression-free survival (PFS) was 3.0 months (95% CI, 0.8–8.2) and median overall survival (OS) 9 months (95% CI, 2.5–20.9). Conclusion This study in heavily pre-treated pancreatic adenocarcinoma patients suggests alternative strategies beyond single agent MEK inhibition are required for this unique, molecular subset of pancreatic cancer patients. The trial was registered on February 2nd, 2017 under identifier NCT03040986 with ClinicalTrials.gov.


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