Cancer-associated thrombosis by cancer sites and inherited factors in a prospective population-based cohort.

Cancer-associated thrombosis (CAT) is common and associated with mortality. We estimated CAT rate by cancer sites and inherited factors among cancer patients from the UK Biobank (N =70,406). The 12-month CAT rate after cancer diagnosis was 2.37% overall but varied considerably among cancer sites. Among the 10 cancer sites classified as 'high-risk' of CAT by the National Comprehensive Cancer Network guidelines, 6 had CAT rate <5%. In contrast, 5 cancer sites classified as 'average-risk' by the guidelines had CAT rate >5%. For inherited risk factors, both known mutation carriers in two genes (F5/F2) and polygenic score for venous thromboembolism (VTE) (PGSVTE) were independently associated with increased CAT risk. While F5/F2 identified 6% patients with high genetic-risk for CAT, adding PGSVTE identified 13 % patients at equivalent/higher genetic-risk to CAT than that of F5/F2 mutations. Findings from this large prospective study, if confirmed, provide critical data to update guidelines for CAT risk assessment.

Primary systemic therapy in resectable pancreatic ductal adenocarcinoma using mFOLFIRINOX: A pilot study.

BACKGROUND AND OBJECTIVES: Surgery followed by gemcitabine and/or a fluoropyrimidine is standard therapy for resectable PDAC. mFOLFIRINOX (oxaliplatin 85 mg/m2 , irinotecan 180 mg/m2 , leucovorin 400 mg/m2 Day 1, 5-FU 2400 mg/m2 × 48 h IV, peg-filgrastim 6 mg SQ day 3, every 14 days) has substantial activity in metastatic PDAC. We wished to determine the tolerability/efficacy of peri-operative mFOLFIRINOX in resectable PDAC. METHODS: Patients with resectable PDAC (ECOG PS 0/1) received four cycles of mFOLFIRINOX pre- and post-surgery. The primary endpoint was completion of preoperative chemotherapy plus resection. Secondary endpoints included completion of all therapy, R0 resection, treatment related toxicity, PFS, and OS. RESULTS: Twenty-one patients enrolled: median age 62 (47-78); 20/21 (95%) completed four cycles of preoperative mFOLFIRINOX; response by RECIST was 1 CR, 3 PR, 16 SD; 17/21 (81%) completed resection, 16/21 (76%) R0; 14/21 (66%) completed four cycles of postoperative mFOLFIRINOX. Grade 3 and 4 toxicity occurred in 23% and 14% patients pre-operatively, 26% and 6.0% post-operatively. Nine patients are alive with median follow-up of 27.7 (3.1-47.1) months. CONCLUSIONS: PST using mFOLFIRINOX in resectable PDAC is feasible and tolerable. R0 resection rate is high and survival promising, requiring longer follow-up and larger studies for definitive assessment.

Wait times for cancer surgery in the United States: trends and predictors of delays.

BACKGROUND: Patients frequently voice concerns regarding wait times for cancer treatment; however, little is known about the length of wait times from diagnosis to surgery in the United States. Our objectives were (1) to assess changes in wait times over the past decade and (2) to identify patient, tumor, and hospital factors associated with prolonged wait times for initial cancer treatment. METHODS: Using the National Cancer Data Base (1995-2005), 1,228,071 patients were identified who underwent resection for nonmetastatic breast, colon, esophageal, gastric, liver, lung, pancreatic, and rectal cancer at 1443 hospitals. Multivariable models were developed to assess factors associated with time to treatment. RESULTS: From 1995 to 2005, the median time from diagnosis to treatment increased for all cancers (P < 0.0001). The time from diagnosis to treatment was significantly longer at National Cancer Institute Comprehensive Cancer Centers and Veterans' Administration institutions versus community hospitals (P < 0.0001). On multivariable analysis, patients were significantly more likely to undergo initial treatment > 30 days from diagnosis if older (6 of 8 cancers), black (5 of 8 cancers), had more comorbidities (6 of 8 cancers), had Stage I disease (7 of 8 cancers), or were treated at National Cancer Institute Comprehensive Cancer Centers or Veterans' Affairs institutions (all cancers). CONCLUSIONS: Wait times for cancer treatment have increased over the last decade. As case loads increase, wait times for treatment are likely to continue increasing, potentially resulting in additional treatment delay. Additional resources and strategies are needed to reduce wait times for cancer treatment in the United States.

Long-term follow-up of a Phase II trial of high-dose radiation with concurrent 5-fluorouracil and cisplatin in patients with anal cancer (ECOG E4292).

PURPOSE: Although chemoradiation using 5-fluorouracil (5-FU) and mitomycin-C (MMC) is the standard of care in the treatment of anal cancer, many patients are unable to tolerate MMC. This Phase II clinical trial was performed to determine whether cisplatin could replace MMC in the treatment of anal cancer. METHODS AND MATERIALS: Thirty-three patients with localized anal cancer were enrolled. One patient registered but never received any assigned therapy and was excluded from all analyses. Between February 1, 1993, and July 21, 1993, 19 patients were accrued to Cohort 1. Radiation consisted of 45 Gy to the primary tumor and pelvic nodes, followed by a boost to the primary and involved nodes to 59.4 Gy. A planned 2-week treatment break was used after 36 Gy. Concurrent chemotherapy consisted of 5-FU 1,000 mg/m(2)/day on Days 1 to 4 and cisplatin 75 mg/m(2) on Day 1. A second course of 5-FU and cisplatin was given after 36 Gy, when the patient resumed radiation therapy. Between April 4, 1996, and September 23, 1996, an additional 13 patients (Cohort 2) were accrued to the study and received the same treatment except without the planned treatment break. RESULTS: Complete response was seen in 78% (90% CI, 63-89) of patients and was higher in patients who did not get a planned treatment break (92% vs. 68%). The overall Grade 4 toxicity rate was 31%. One treatment-related death (Grade 5) occurred in a patient who developed sepsis. The 5-year overall survival was 69%. CONCLUSIONS: Radiation therapy, cisplatin, and 5-FU resulted in an overall objective response (complete response + partial response) of 97%. Although the 5-year progression-free survival was only 55%, the overall 5-year survival was 69%. Given the excellent salvage provided by surgery, this study affirms that cisplatin-based regimens may be an alternative for patients who cannot tolerate the severe hematologic toxicities associated with mitomycin-based chemoradiation regimens.

Lymph node evaluation as a colon cancer quality measure: a national hospital report card.

BACKGROUND: Examination of 12 or more regional lymph nodes for colon cancer is associated with improved staging and survival, and the National Quality Forum recently endorsed lymph node examination for colon cancer as a quality surveillance measure. However, information regarding the extent of hospital compliance with the 12-node measure in the United States is lacking. METHODS: From the National Cancer Data Base, 1296 hospitals that performed 156 789 colectomies in 1996-1997 and 2004-2005 were identified, and rates of hospital-level compliance (defined as examination of >or=12 nodes in >or=75% of patients) in these two time periods were compared. Multivariable models were developed to determine if hospital type, volume, or differences in case mix were associated with 12-node measure compliance. All statistical tests were two-sided. RESULTS: In 1996-1997, 15% of hospitals were compliant with the 12-node measure; in 2004-2005 the percentage of compliant hospitals had increased to 38%. From 1996-1997 to 2004-2005, 12-node measure compliance increased at 980 hospitals, remained unchanged at 6 hospitals, and decreased at 310 hospitals. In 2004-2005, National Cancer Institute-designated Comprehensive Cancer Centers were more frequently compliant with the 12-node measure than other academic hospitals, Veterans' Administration hospitals, or community hospitals (78.1% versus 52.4%, 53.1%, and 33.7%, respectively, all P < .001), even after adjustment for differences in characteristics of the colon cancer patients at these hospitals. CONCLUSIONS: This study provides a national report card of nearly 1300 hospitals showing that more than 60% of institutions failed to achieve a compliance benchmark for the 12-node measure. Considerable improvement is needed in colon cancer nodal evaluation in the United States.

Effect of hospital type and volume on lymph node evaluation for gastric and pancreatic cancer.

HYPOTHESIS: For gastric and pancreatic cancer, regional lymph node evaluation is important to accurately stage disease in a patient and may be associated with improved survival. We hypothesized that National Comprehensive Cancer Network (NCCN), National Cancer Institute (NCI)-designated institutions, and high-volume hospitals examine more lymph nodes for gastric and pancreatic malignant neoplasms than do low-volume centers and community hospitals. DESIGN: Volume-outcome study. SETTING: Academic research. PATIENTS: Using the National Cancer Data Base (January 1, 2003, to December 31, 2004), patients were identified who underwent resection for gastric (n = 3088) and pancreatic (n = 1130 [pancreaticoduodenectomy only]) cancer. MAIN OUTCOME MEASURES: Multivariable logistic regression analysis was used to assess the effect of hospital type and volume on nodal evaluation (>or=15 nodes). RESULTS: Only 23.2% of patients with gastric cancer and 16.4% of patients with pancreatic cancer in the United States underwent evaluation of at least 15 lymph nodes. Patients undergoing surgery had more lymph nodes examined at NCCN-NCI hospitals than at community hospitals (median, 12 vs 6 for gastric cancer and 9 vs 6 for pancreatic cancer; P < .001). Patients at highest-volume hospitals had more lymph nodes examined than patients at low-volume hospitals (median, 10 vs 6 for gastric cancer and 8 vs 6 for pancreatic cancer; P < .001). On multivariable analysis, patients undergoing surgery at NCCN-NCI and high-volume hospitals were more likely to have at least 15 lymph nodes evaluated compared with patients undergoing surgery at community hospitals and low-volume centers (P < .001 and P =.02, respectively). CONCLUSIONS: Nodal examination is important for staging, adjuvant therapy decision making, and clinical trial stratification. Moreover, differences in nodal evaluation may contribute to improved long-term outcomes at NCCN-NCI centers and high-volume hospitals for patients with gastric and pancreatic cancer.

National failure to operate on early stage pancreatic cancer.

BACKGROUND: Despite studies demonstrating improved outcomes, pessimism persists regarding the effectiveness of surgery for pancreatic cancer. Our objective was to evaluate utilization of surgery in early stage disease and identify factors predicting failure to undergo surgery. METHODS: Using the National Cancer Data Base (1995-2004), 9559 patients were identified with potentially resectable tumors (pretreatment clinical Stage I: T1N0M0 and T2N0M0). Multivariate models were employed to identify factors predicting failure to undergo surgery and assess the impact of pancreatectomy on survival. RESULTS: Of clinical Stage I patients 71.4% (6823/9559) did not undergo surgery; 6.4% (616/9559) were excluded due to comorbidities; 4.2% (403/9559) refused surgery; 9.1% (869/9559) were excluded due to age; and 38.2% (3,644/9559) with potentially resectable cancers were classified as "not offered surgery." Of the 28.6% (2736/9559) of patients who underwent surgery, 96.0% (2630/2736) underwent pancreatectomy, and 4.0% (458/2736) had unresectable tumors. Patients were less likely to undergo surgery if they were older than 65 years, were black, were on Medicare or Medicaid, had pancreatic head lesions, earned lower annual incomes, or had less education (P < 0.0001). Patients were less likely to receive surgery at low-volume and community centers. Patients underwent surgery more frequently at National Cancer Institute/National Comprehensive Cancer Network-designated cancer centers (P < 0.0001). Patients who were not offered surgery had significantly better survival than those with Stage III or IV disease but worse survival than patients who underwent pancreatectomy for Stage I disease (P < 0.0001). CONCLUSIONS: This is the first study to characterize the striking underuse of pancreatectomy in the United States. Of early stage pancreatic cancer patients without any identifiable contraindications, 38.2% failed to undergo surgery.