Person:

Kwak, Eunice Lee

Targeted cancer therapy requires the rapid and accurate identification of genetic abnormalities predictive of therapeutic response. We sought to develop a high-throughput genotyping platform that would allow prospective patient selection to the best available therapies, and that could readily and inexpensively be adopted by most clinical laboratories. We developed a highly sensitive multiplexed clinical assay that performs very well with nucleic acid derived from formalin fixation and paraffin embedding (FFPE) tissue, and tests for 120 previously described mutations in 13 cancer genes. Genetic profiling of 250 primary tumours was consistent with the documented oncogene mutational spectrum and identified rare events in some cancer types. The assay is currently being used for clinical testing of tumour samples and contributing to cancer patient management. This work therefore establishes a platform for real-time targeted genotyping that can be widely adopted. We expect that efforts like this one will play an increasingly important role in cancer management.

Objective: Patients who undergo an R0 resection of their pancreatic ductal adenocarcinoma (PDAC) have an improved survival compared with patients who undergo an R1 resection. It is unclear whether an R1 resection confers a survival benefit over locally advanced (LA) unresectable tumors. Our aim was to compare the survival of patients undergoing an R1 resection with those having LA tumors and to explore the prognostic significance of a 1-mm surgical margin. Methods: Clinicopathologic data from a pancreatic cancer database between January 1993 and July 2008 were reviewed. Locally advanced tumors had no evidence of metastatic disease at exploration. Results: A total of 1705 patients were evaluated for PDAC in the Department of Surgery. Of the 1084 (64%) patients who were surgically explored, 530 (49%) were considered unresectable (286 locally unresectable, 244 with distant metastasis). One hundred fifty-seven (28%) of the resected PDACs had an R1 resection. Patients undergoing an R1 resection had a slightly longer survival compared with those who had locally advanced unresectable cancers (14 vs 11 months; P < 0.001). Patients with R0 resections had a favorable survival compared with those with R1 resections (23 vs 14 months; P < 0.001), but survival after resections with 1-mm margin or less (R0-close) were similar to R1 resections: both groups had a significantly shorter median survival than patients with a margin of greater than 1 mm (R0-wide) (16 vs 14 vs 35 months, respectively; P < 0.001). Conclusions: Patients undergoing an R1 resection still have an improved survival compared with patients with locally advanced unresectable pancreatic adenocarcinoma. R0 resections have an improved survival compared with R1 resections, but this survival benefit is lost when the tumor is within 1 mm of the resection margin.

Background: The benefit of surgical resection in patients with incurable gastric adenocarcinoma is controversial. Methods: A total of 289 patients who presented with advanced or metastatic gastric cancer from 1995 to 2010 were retrospectively reviewed. Results: Ten patients (3.5 %) required emergent surgery at presentation and were excluded from further analyses. Patients who underwent nonemergent surgery at presentation (n = 110, 38.1 %) received either gastric resection (group A, n = 46, 42 %) or surgery without resection (group B, n = 64, 58 %). Procedures in group A included distal gastrectomy (n = 25, 54 %), total gastrectomy (n = 17, 37 %), and proximal/esophagogastrectomy (n = 4, 9 %). Procedures in group B included laparoscopy (n = 17, 27 %), open exploration (n = 25, 39 %), gastrostomy and/or jejunostomy tube (n = 12, 19 %), and gastrojejunostomy (n = 10, 16 %). Group A required a stay in the intensive care unit or additional invasive procedure significantly more often than group B (15 vs. 2 %, p = 0.009). Four patients in group A (8.7 %) and three patients in group B (4.7 %) died within 30 days of surgery (p = 0.45). When the 110 patients who underwent nonemergent surgery (groups A and B) were compared to nonoperatively managed patients (group C, n = 169, 58 %), median overall survival did not significantly differ (8.6 vs. 9.2 vs. 7.7 months; p > 0.05). Three patients in group B (4.7 %) and three in group C (1.8 %) ultimately required an operation for their primary tumor. Conclusions: Patients with gastric adenocarcinoma who present with advanced or metastatic disease not amenable to curative resection infrequently require emergent surgery. Noncurative resection is associated with significant perioperative morbidity and mortality as well as limited overall survival, and should therefore be performed judiciously.