Nagorney, David M.

Objectives Prognostic factors for solid pseudopapillary neoplasms (SPN) of the pancreas have been incompletely defined in the literature. We aimed to use the National Cancer Database to describe survival and characterize prognostic factors in patients with pancreatic pseudopapillary neoplasms. Methods We identified 304 patients with pancreatic SPN diagnosed between 2004 and 2012 using the National Cancer Database. All patients were included in the survival analysis. Kaplan-Meier method, χ 2 , and log-rank tests were used for statistical analysis. Cox proportional hazard regression model was used for multivariate analysis. Results The median age at diagnosis was 36.5 years. Eighty-five percent of patients were female, 69% were white, and 25% were black. Metastases were observed in 5% of patients. Median tumor size was 5.1 cm. Ninety-two percent of patients underwent primary tumor resection. At 60 months, 98% of patients who underwent resection were alive, and 40% who did not undergo resection were alive. On multivariate analysis, female sex, resection of primary tumor, and absence of metastasis were correlated with improved survival. Conclusions Patients with SPN who undergo resection have an excellent survival at 5 years. Surgery should be considered in all patients with this diagnosis.

Abstract Background Deficiencies in the DNA mismatch repair system cause errors during DNA replication, which in turn give rise to microsatellite instability (MSI). The impact of MSI on survival in metastatic colorectal cancer (mCRC) is unclear. This cohort study aims to investigate the prognostic and predictive value of MSI in mCRC prior to the immune therapy era. Materials and Methods A total of 75 MSI-high (MSI-H) mCRC patients (pts) and 75 matched (age, gender, disease sidedness, metachronous/synchronous) microsatellite-stable (MSS) mCRC pts were identified from 1,268 mCRC pts who had MSI/mismatch repair test results at Mayo Clinic Rochester between January 1992 and July 2016. A retrospective review was conducted by using data from electronic medical records. Statistical analyses utilized the Kaplan-Meier method, log-rank test, and Cox proportional hazards models. Results The MSS group was well matched to the MSI-H group based on age, gender, location, and chronicity of metastatic disease. MSI-H mCRC pts had earlier disease recurrence (median time from initial diagnosis to metastatic disease diagnosis, MSI-H group 12.9 vs. MSS group 20.9 months, p = .034). Median overall survival (OS) was 28.1 and 37.4 months for MSI-H and MSS pts, respectively (p = .99). In total, 94.7% of MSI-H pts and 98.7% of MSS pts had fluoropyrimidine-based chemotherapy for metastatic disease, and there was no difference in OS between these two groups (32.3 vs. 37.4 months, p = .91). Forty-three MSI-H and thirty-nine MSS pts had metastasectomy and/or ablation of metastases (p = .51) with longer median OS compared with pts without metastasectomy (MSI-H: 82.0 vs. 13.9, p < .001; MSS: 69.9 vs. 19.7, p < .001). Age <65 years, BRAF wild type, and metastasectomy were associated with better OS in univariate analysis. Only metastasectomy remained statistically significant in multivariate analysis (p < .001). Conclusion In mCRC, patients with MSI-H tumors have similar, but numerically shorter, median overall survival compared with those with MSS tumors. In both groups, metastasectomy and ablation of metastatic disease should be considered to optimize OS. Implications for Practice This study clearly demonstrated the survival benefits that aggressive metastasectomy provides in selected microsatellite instability-high metastatic colorectal cancer patients. This could be meaningful practice-changing information that has been long awaited.

Abstract Background The purpose of this study was to define survival rates in patients with isolated advanced abdominal nodal metastases secondary to colorectal cancer (CRC), treated with curative-intent trimodality therapy. Materials and Methods Sixty-five patients received trimodality therapy, defined as chemotherapy delivered with external beam radiotherapy (EBRT) followed by lymphadenectomy and intraoperative radiotherapy (IORT). Infusional 5-fluorouracil was the most common radiosensitizer used (63%, 41 patients). The median dose of EBRT was 50 Gy, and the median dose of IORT was 12.5 Gy. We evaluated time to distant metastasis, toxicities, local failure within the EBRT field, recurrence within the IORT field, and survival. Results Fifty-two percent of patients were male; patients’ median age was 50.5 years. All patients had an Eastern Cooperative Oncology Group score ≤1. Twenty-nine patients had right-sided colon cancer, 22 had left-sided colon cancer, and 14 had rectal primaries. The median time from initial CRC diagnosis to development of abdominal nodal metastatic disease was 20.6 months (95% confidence interval [CI], 21.2–40.8 months). Seventy-eight percent (51 patients) had para-aortic nodal metastases, 15% (10 patients) had mesenteric nodal metastases, and 6% (4 patients) had both. With a median follow-up of 77.6 months, the median overall survival and 5-year estimated survival rate were 55.4 months (95% CI, 47.2–80.9 months) and 45%, respectively. The median progression-free survival was 19.3 months (95% CI, 16.5–32.8 months). Twenty-six (40%) patients never developed distant disease. The outcome was not affected by disease sidedness or rectal primary. Treatment was well tolerated without grade 3 or 4 toxicities. Conclusion Trimodality therapy produces sustainable long-term survival in selected patients with metastatic CRC presenting with isolated retroperitoneal or mesenteric nodal relapse. Implications for Practice This article reports a unique trimodality approach incorporating external beam radiotherapy with radiosensitizing chemotherapy, surgical resection, and intraoperative radiotherapy provides durable survival benefit with significant curative potential for patients with metastatic colorectal cancer who present with isolated abdominal nodal (mesenteric and/or retroperitoneal) recurrence.

Abstract Background BRAF V600E mutations are present in 8%–10% of patients with metastatic colorectal cancer (mCRC) and portend poor prognosis. This study investigated the impact of metastasectomy for patients with BRAF V600E mCRC. Subjects, Materials, and Methods Using prospective clinical and molecular data, patients with BRAF V600E mCRC were analyzed for clinical characteristics and survival. Statistical analyses utilized the Kaplan-Meier method, log-rank test, and Cox proportional hazard models. Results Fifty-two patients were identified between July 1, 2008, and January 4, 2016. Patient characteristics included median age 65 years, 61% female, Eastern Cooperative Oncology Group performance status ≤1, 71% with right-sided tumors, and 28% with liver-limited metastasis. In the first-line setting, 7% (4/52) received fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI)/bevacizumab (BEV) and 81% were treated with doublet chemotherapy consisting of fluoropyrimidine, oxaliplatin, and BEV. Median overall survival (OS) for all 52 patients was 25 months with median progression-free survival (PFS) of 9.3 months. With median follow-up of 18.3 months, 21 patients underwent metastasectomy with longer OS (29.1 months vs. 22.7 months, hazard ratio [HR] = 0.33; confidence interval [CI], 0.12–0.78; p = .01) and PFS (13.6 months vs. 6.2 months, HR = 0.53, CI, 0.28–0.97; p = .03) compared with the non-metastasectomy cohort. In multivariate analysis, metastasectomy remained significant for improved survival outcomes (HR = 0.52; 95% CI, 0.07–1.02; p = .02). Median disease-free survival after metastasectomy was 9.7 months (95% CI, 5.5–19.5). Two patients remain disease-free at the time of last follow-up, with one patient without relapse for greater than 2 years (28.9 months). Conclusion Multimodality therapy incorporating metastasectomy for BRAF V600E mCRC should be considered and might be associated with improved overall survival in select patients. Implications for Practice BRAF V600E metastatic colorectal cancer (mCRC) represents an extremely difficult molecular subset of colorectal cancer to treat. To date, this subset remains refractory to standard chemotherapies, prompting extensive clinical investigation regarding novel treatment approaches and targeted modalities. While the use of metastasectomy for expanded RAS wild-type and RAS mutated mCRC has resulted in improved overall survival for select patients, utilization of metastasectomy in patients with BRAF V600E mCRC remains controversial. This article explores the authors' experience with BRAF V600E mCRC to ascertain whether a multidisciplinary approach incorporating metastasectomy for well-selected patients improves overall survival.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. In select patients, surgical treatment in the form of either resection or transplantation offers a curative option. The aims of this review are to (1) review the current American Association for the Study of Liver Diseases/European Association for the Study of the Liver guidelines on the surgical management of HCC and (2) review the proposed changes to these guidelines and analyze the strength of evidence underlying these proposals. Three authors identified the most relevant publications in the literature on liver resection and transplantation for HCC and analyzed the strength of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification. In the United States, the liver allocation system provides priority for liver transplantation to patients with HCC within the Milan criteria. Current evidence suggests that liver transplantation may also be indicated in certain patient groups beyond Milan criteria, such as pediatric patients with large tumor burden or adult patients who are successfully downstaged. Patients with no underlying liver disease may also benefit from liver transplantation if the HCC is unresectable. In patients with no or minimal (compensated) liver disease and solitary HCC ≥2 cm, liver resection is warranted. If liver transplantation is not available or contraindicated, liver resection can be offered to patients with multinodular HCC, provided that the underlying liver disease is not decompensated. Many patients may benefit from surgical strategies adapted to local resources and policies (hepatitis B prevalence, organ availability, etc). Although current low-quality evidence shows better overall survival with aggressive surgical strategies, this approach is limited to select patients. Larger and well-designed prospective studies are needed to better define the benefits and limits of such approach.

AbstractPalliative treatment in myelofibrosis (MF) includes transfusion support, JAK2 inhibitors, involved field radiotherapy and splenectomy. To assist in selecting patients who are likely to benefit from splenectomy, we looked into risk factors for postsplenectomy survival, in 120 consecutive cases (median age 66 years); at the time of splenectomy, 61% displayed red cell transfusion need, 49% platelet count <100 × 10(9)/L, 25% leukocyte count >25 × 10(9)/L, 60% constitutional symptoms and 13% circulating blasts ≥5%; dynamic international prognostic scoring system risk categories were 21% high, 55% intermediate‐2, 21% intermediate‐1 and 3% low. Among informative cases, karyotype was abnormal in 60% and driver mutational status was JAK2 75%, CALR 15%, MPL 4% and triple‐negative 6%. At median follow‐up of 1.3 years, from time of splenectomy, 95 (79%) deaths and 30 (25%) leukemic transformations were recorded. Median postsplenectomy survival was 1.5 years; in multivariable analysis, survival was adversely affected by age >65 years, transfusion need, leukocyte count >25 × 10(9)/L and circulating blasts ≥5%; these variables were subsequently used to devise an HR‐weighted scoring system with high (3‐4 risk factors), intermediate (2 risk factors) and low (0‐1 risk factors) risk categories; the corresponding postsplenectomy median survivals were 0.3 (HR 5.9, 95% CI 3.2‐11.0), 1.3 (HR 2.9, 95% CI 1.8‐4.6) and 2.9 years. Postsplenectomy survival was not affected by driver mutational status or occurrence of leukemic transformation. Leukemia‐free survival was predicted by very high risk karyotype. The observations from the current study might help identify appropriate candidates for splenectomy in MF.

535 Background: The most effective management of locally recurrent colorectal cancer (CRC) is resection. This is also true for hepatic metastases (HM). Data remains limited, however, regarding concomitant resection of recurrent CRC and HM. The aims of this study were to determine the feasibility, safety and outcomes in terms of disease-free survival (DFS) and overall survival (OS) in patients undergoing concomitant resection of recurrent CRC with HM. Methods: All patients who underwent resection of recurrent CRC from 1/1995 to 1/2007 at Mayo Clinic, Rochester were reviewed (n=406). The study group consisted of patients who underwentconcomitant resection of locally recurrent CRC and hepatic resection for metastatic CRC (n= 45). Kaplan-Meier Survival was used to estimate DFS and OS. Results: The study group consisted of 27 men and 18 women. The median age was 59 years. Surgical management involved pelvic dissection in 43 patients and ileotransverse colectomy in two. 17 patients required resection of contiguous organs. 24 patients received intra-operative radiation. 34 patients underwent multiple hepatic wedge resections, 6 patients segmentectomy, 3 left hepatectomy, and 2 right hepatectomy. There was no perioperative mortality. Morbidity was 37%, 2 patients required re-operation. The 1, 3, and 5 year DFS was 72.2, 42.3, and 18.5%, respectively. The 1, 3, and 5 year OS was 87.7, 47.6, and 36.2%, respectively. Conclusions: Synchronous resection of locally recurrent CRC and HM is safe and feasible; morbidity is reasonable and mortality zero. DFS and OS in this patient population appear comparable to that of patients undergoing separate, staged resections.