Prior molecular profiling of hepatocellular carcinoma (HCC) has identified actionable findings that may have a role in guiding therapeutic decision-making and clinical trial enrollment. We ...implemented prospective next-generation sequencing (NGS) in the clinic to determine whether such analyses provide predictive and/or prognostic information for HCC patients treated with contemporary systemic therapies.
Matched tumor/normal DNA from patients with HCC (
= 127) were analyzed using a hybridization capture-based NGS assay designed to target 341 or more cancer-associated genes. Demographic and treatment data were prospectively collected with the goal of correlating treatment outcomes and drug response with molecular profiles.
WNT/β-catenin pathway (45%) and
(33%) alterations were frequent and represented mutually exclusive molecular subsets. In sorafenib-treated patients (
= 81), oncogenic PI3K-mTOR pathway alterations were associated with lower disease control rates (DCR, 8.3% vs. 40.2%), shorter median progression-free survival (PFS; 1.9 vs. 5.3 months), and shorter median overall survival (OS; 10.4 vs. 17.9 months). For patients treated with immune checkpoint inhibitors (
= 31), activating alteration WNT/β-catenin signaling were associated with lower DCR (0% vs. 53%), shorter median PFS (2.0 vs. 7.4 months), and shorter median OS (9.1 vs. 15.2 months). Twenty-four percent of patients harbored potentially actionable alterations including
(8.5%) inactivating/truncating mutations,
(6.3%) and
(1.5%) amplifications, and
missense mutations (<1%). Six percent of patients treated with systemic therapy were matched to targeted therapeutics.
Linking NGS to routine clinical care has the potential to identify those patients with HCC likely to benefit from standard systemic therapies and can be used in an investigational context to match patients to genome-directed targeted therapies.
.
Background The indications for minimally invasive (MIS) pancreatectomy have slowly increased as experience, techniques, and technology have improved and evolved to manage malignant lesions in ...selected patients without compromising safety and oncologic principles. There are sparse data comparing laparoscopic, robotic, and open distal pancreatectomy (DP). Study Design All patients undergoing DP at Memorial Sloan Kettering Cancer Center between 2000 and 2013 were analyzed from a prospective database. Clinicopathologic and survival data were analyzed to compare perioperative and oncologic outcomes in patients who underwent DP via open, laparoscopic, and robotic approaches. Results Eight hundred five DP were performed during the study period, comprising 37 robotic distal pancreatectomies (RDP), 131 laparoscopic distal pancreatectomies (LDP), and 637 open distal pancreatectomies (ODP). The 3 groups were similar with respect to American Society of Anesthesiologists (ASA) score, sex ratio, body mass index, pancreatic fistula rate, and 90-day morbidity and mortality. Patients in the ODP group were generally older (p = 0.001), had significantly higher intraoperative blood loss (p < 0.001), and had a trend toward a longer hospital stay (p = 0.05). Of the significant preoperative variables, visceral fat was predictive of conversion on multivariate analysis (p = 0.003). Oncologic outcomes in the adenocarcinoma cases were similar for the 3 groups, with high rates of R0 resection (88% to 100%). The ODP group had a higher lymph node yield than the LDP and RDP groups (15.4, SD 8.7 vs 10.4 SD 8.0 vs 12SD 7.2, p = 0.04). Conclusions The RDP and LDP were comparable with respect to most perioperative outcomes, with no clear advantage of one approach over the other. Both of these MIS techniques may have advantages over ODP in well-selected patients. All approaches achieved a similarly high rate of R0 resection for patients with adenocarcinoma.
Pasireotide for Postoperative Pancreatic Fistula Allen, Peter J; Gönen, Mithat; Brennan, Murray F ...
New England journal of medicine/The New England journal of medicine,
05/2014, Volume:
370, Issue:
21
Journal Article
Peer reviewed
Open access
Postoperative pancreatic fistula is a common complication of pancreatic surgery. In this trial, patients undergoing pancreatic resection who received pasireotide, a somatostatin analogue, had a ...decreased occurrence of postoperative pancreatic fistula, leak, or abscess.
Although mortality after pancreatectomy has decreased to approximately 2% at high-volume centers, the operative morbidity after these procedures has remained between 30% and 50%.
1
,
2
Postoperative pancreatic fistula, leak, and abscess are complications that result from leakage of pancreatic exocrine secretions at the anastomosis or closure of the pancreatic remnant. Postoperative pancreatic fistula is the most common major complication after pancreatectomy, with reported rates between 10% and 28%. Studies suggest that patients in whom postoperative pancreatic fistula develops have a risk of death that is approximately doubled.
3
,
4
Because of the magnitude of this problem, numerous studies have investigated methods . . .
Background Liver resection is used to treat primary and secondary malignancies. Historically, these procedures were associated with significant complications, which may affect cancer-specific ...outcomes. This study analyzed the changes in morbidity and mortality after hepatic resection over time. Study Design Records of all patients undergoing liver resection for a malignant diagnosis from 1993 to 2012 at Memorial Sloan Kettering were analyzed. Patients were divided into early (1993 to 1999), middle (2000 to 2006), and recent (2007 to 2012) eras. Major hepatectomy was defined as resection of 3 or more segments. Univariate and multivariate analyses were made with t -tests or Mann-Whitney tests. Results There were 3,875 patients who underwent 4,152 resections for malignancy. The most common diagnosis was metastatic colorectal cancer (n = 2,476, 64% of patients). Over the study period, 90-day mortality rate decreased from 5% to 1.6% (p < 0.001). Perioperative morbidity decreased from 53% to 20% (p < 0.001). The percentage of major hepatectomies decreased from 66% to 36% (p < 0.001). The rate of perioperative transfusion decreased from 51% to 21% (p < 0.001). The spectrum of perioperative morbidity changed markedly over time, with abdominal infections (43% of complications) overtaking cardiopulmonary complications (22% of complications). Peak postoperative bilirubin (odds ratio OR 1.1, p < 0.001), blood loss (OR 1.5, p = 0.001), major hepatectomy (OR 1.3, p = 0.031), and concurrent partial colectomy (OR 2.4, p < 0.001) were independent predictors of perioperative morbidity. The mortality associated with trisectionectomy (6%) and right hepatectomy (3%) remained unchanged over time. Conclusions Morbidity and mortality rates after partial hepatectomy for cancer have decreased substantially as the major hepatectomy rate has dropped. Encouraging parenchymal preservation and preventing abdominal infections are vital for continued improvement of liver resection outcomes.
Background
The impact of primary tumor location on overall survival (OS), recurrence-free survival (RFS), and long-term outcomes has not been well established in patients undergoing potentially ...curative resection of colorectal liver metastases (CRLM).
Methods
A single-institution database was queried for initial resections for CRLM 1992–2004. Primary tumor location determined by chart review (right = cecum to transverse; left = splenic flexure to sigmoid). Rectal cancer (distal 16 cm), multiple primaries, and unknown location were excluded. Kaplan–Meier and Cox regression methods were used. Cure was defined as actual 10-year survival with either no recurrence or resected recurrence with at least 3 years of disease-free follow-up.
Results
A total of 907 patients were included with a median follow-up of 11 years; 578 patients (64%) had left-sided and 329 (36%) right-sided primaries. Median OS for patients with a left-sided primary was 5.2 years (95% confidence interval CI 4.6–6.0) versus 3.6 years (95% CI 3.2–4.2) for right-sided (
p
= 0.004). On multivariable analysis, the hazard ratio for right-sided tumors was 1.22 (95% CI 1.02–1.45,
p
= 0.028) after adjusting for common clinicopathologic factors. Median RFS was marginally different stratified by primary location (1.3 vs. 1.7 years;
p
= 0.065). On multivariable analysis, location of primary was not significantly associated with RFS (
p
= 0.105). Observed cure rates were 22% for left-sided and 20% for right-sided tumors.
Conclusions
Among patients undergoing resection of CRLM, left-sided primary tumors were associated with improved median OS. However, long-term survival and recurrence-free survival were not significantly different stratified by primary location. Patients with left-sided primary tumors displayed a prolonged clinical course suggestive of more indolent biology.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Background Liver resection is the most effective treatment for intrahepatic cholangiocarcinoma (IHCC). Recurrent disease is frequent, however, recurrence patterns are ill-defined, and ...prognostic models are lacking. Study Design A primary cohort of 189 patients who underwent resection for IHCC was used for recurrence patterns analysis within and after 24 months. Based on independent factors for disease free survival (DFS) identified in Cox regression analysis, preoperative and postoperative models were developed using a recursive partitioning method. Models were externally validated using a multicenter cohort of 522 resected patients (Association Française de Chirurgie-IHCC study group). Results Recurrence within 24 months most often involved the liver (82.7%) while most recurrences after 24 months were strictly extrahepatic (61.1%). In multivariable analysis of the primary cohort, independent preoperative factors for DFS were tumor size and multifocality (based on imaging), while tumor size, multifocality, vascular invasion and lymph node metastases (based on pathology) were independent postoperative factors. The preoperative model allowed patient classification into low risk and high risk groups for recurrence. In the validation cohort (n=522), high risk patients had a greater likelihood of recurrence (HR=2.17, 95% CI 1.74-2.72; p<0.001). Postoperative model included tumor size, vascular invasion and positive nodal disease on pathology and classified patients in low, intermediate and high risk groups in the primary cohort. As compared to low risk patients in the validation cohort, intermediate and high risk patients were more likely to experience recurrence (HR=1.9, 95% CI 1.41-2.47; p<0.001 and HR=2.99, 95% CI 2.08-4.31; p<0.001, respectively). Conclusions Recurrence patterns are time dependent. Both models as developed and validated in this study classified patients in distinct recurrence risk groups, which may guide treatment recommendations.
Background Liver surgery for perihilar cholangiocarcinoma (PHC) is associated with postoperative mortality ranging from 5% to 18%. The aim of this study was to develop a preoperative risk score for ...postoperative mortality after liver resection for PHC, and to assess the effect of biliary drainage of the future liver remnant (FLR). Study Design A consecutive series of 287 patients submitted to major liver resection for presumed PHC between 1997 and 2014 at 2 Western centers was analyzed; 228 patients (79%) underwent preoperative drainage for jaundice. Future liver remnant volumes were calculated with CT volumetry and completeness of FLR drainage was assessed on imaging. Logistic regression was used to develop a mortality risk score. Results Postoperative mortality at 90 days was 14% and was independently predicted by age (odds ratio OR per 10 years = 2.1), preoperative cholangitis (OR = 4.1), FLR volume <30% (OR = 2.9), portal vein reconstruction (OR = 2.3), and incomplete FLR drainage in patients with FLR volume <50% (OR = 2.8). The risk score showed good discrimination (area under the curve = 0.75 after bootstrap validation) and ranking patients in tertiles identified 3 (ie low, intermediate, and high) risk subgroups with predicted mortalities of 2%, 11%, and 37%. No postoperative mortality was observed in 33 undrained patients with FLR volumes >50%, including 10 jaundiced patients (median bilirubin level 11 mg/dL). Conclusions The mortality risk score for patients with resectable PHC can be used for patient counseling and identification of modifiable risk factors, which include FLR volume, FLR drainage status, and preoperative cholangitis. We found no evidence to support preoperative biliary drainage in patients with an FLR volume >50%.
Background Published prognostic models for overall survival after liver resection for intrahepatic cholangiocarcinoma require external validation before use in clinical practice. Study Design From ...January 1993 to May 2013, consecutive patients who underwent resection of intrahepatic cholangiocarcinoma were identified from a prospective database. The Wang nomogram was derived in an Asian cohort (n = 367) and included clinicopathologic variables and preoperative CEA and cancer antigen 19-9 levels. The Hyder nomogram was derived in an Eastern and Western multicenter cohort (n = 514) using clinicopathologic variables only. The AJCC Cancer Staging System (7th ed) and the preoperative Fudan risk score were also evaluated. Prognostic performance was assessed in terms of discrimination, calibration, and stratification. Results One hundred and eighty-eight patients were included, with a median follow-up of 41 months. Median overall survival was 48.7 months and estimated 3-year and 5-year overall survival rates were 59% and 45%, respectively. Overall survival prediction accuracy, according to concordance-index calculation, was 0.72 with the Wang nomogram, 0.66 with the Hyder nomogram, 0.63 with the AJCC system, and 0.55 using the Fudan score. Both nomograms provided effective patient stratification in distinct survival groups. Conclusions Both the Wang and Hyder nomograms provided accurate patient prognosis estimation after liver resection for intrahepatic cholangiocarcinoma and can be useful for decision making about adjuvant therapy. The Wang nomogram appears to be more appropriate in patients undergoing formal portal lymphadenectomy and requires preoperative CEA and cancer antigen 19-9 levels for optimal performance.
Microvascular invasion (MVI) is a significant risk factor for early recurrence after resection or transplantation for hepatocellular carcinoma (HCC). Knowledge of MVI status would help guide ...treatment recommendations, but is generally identified after operation. This study aims to predict MVI preoperatively using quantitative image analysis.
One hundred and twenty patients from 2 institutions underwent resection of HCC from 2003 to 2015 were included. The largest tumor from preoperative CT was subjected to quantitative image analysis, which uses an automated computer algorithm to capture regional variation in CT enhancement patterns. Quantitative imaging features by automatic analysis, qualitative radiographic descriptors by 2 radiologists, and preoperative clinical variables were included in multivariate analysis to predict histologic MVI.
Histologic MVI was identified in 19 (37%) patients with tumors ≤5 cm and 34 (49%) patients with tumors >5 cm. Among patients with tumors ≤5 cm, none of the clinical findings or radiographic descriptors were associated with MVI; however, quantitative features based on angle co-occurrence matrix predicted MVI with an area under curve of 0.80, positive predictive value of 63%, and negative predictive value of 85%. In patients with tumors >5 cm, higher α-fetoprotein level, larger tumor size, and viral hepatitis history were associated with MVI, and radiographic descriptors were not. However, a multivariate model combining α-fetoprotein, tumor size, hepatitis status, and quantitative feature based on local binary pattern predicted MVI with area under curve of 0.88, positive predictive value of 72%, and negative predictive value of 96%.
This study reveals the potential importance of quantitative image analysis as a predictor of MVI.
PDF
