A USA registry of gastrointestinal stromal tumor patients: changes in practice over time and differences between community and academic practices.

BACKGROUND: The objective of the study was to describe patterns of care of patients with gastrointestinal stromal tumors (GISTs) in the United States in the tyrosine kinase inhibitor (TKI) era. PATIENTS AND METHODS: From November 2004 through March 2009, data were collected regarding demographics, diagnostic history, treatment, relapse, and survival of 882 patients with GIST from 122 community and academic medical practices. RESULTS: The most common first-line treatment for the 719 patients presenting with localized GIST was surgery (87%). Use of adjuvant imatinib increased after June 2007; 47% of patients enrolled in the registry considered by the investigator to be at high risk for recurrence received adjuvant imatinib after June 2007 versus 18% before. Overall, 56% of patients received imatinib and 11% received sunitinib. The utilization of targeted therapy increased over time (45% and 0.4% of patients received imatinib and sunitinib, respectively, in 2006 versus 56% and 11%, respectively, in 2009). CONCLUSIONS: These are the first GIST registry data from the TKI era. The use of targeted therapy for GIST has increased in accordance with updated treatment guidelines. Diagnosis of GIST has evolved with increased use of KIT testing. The duration of targeted therapy in the adjuvant therapy setting is similar in community and academic practices.

Multicenter phase II trial of adjuvant therapy for resected pancreatic cancer using cisplatin, 5-fluorouracil, and interferon-alfa-2b-based chemoradiation: ACOSOG Trial Z05031.

BACKGROUND: The American College of Surgeons Oncology Group sought to confirm the efficacy of a novel interferon-based chemoradiation regimen in a multicenter phase II trial. PATIENTS AND METHODS: Patients with resected (R0/R1) adenocarcinoma of the pancreatic head were treated with adjuvant interferon-alfa-2b (3 million units s.c. on days 1, 3, and 5 of each week for 5.5 weeks), cisplatin (30 mg/m(2) i.v. weekly for 6 weeks), and continuous infusion 5-fluorouracil (5-FU; 175 mg·m(2)/day for 38 days) concurrently with external-beam radiation (50.4 Gy). Chemoradiation was followed by two 6-week courses of continuous infusion 5-FU (200 mg·m(2)/day). The primary study end point was 18-month overall survival from protocol enrollment (OS18); an OS18 ≥65% was considered a positive study outcome. RESULTS: Eighty-nine patients were enrolled. Eighty-four patients were assessable for toxicity. The all-cause grade ≥3 toxicity rate was 95% (80 patients) during therapy. No long-term toxicity or toxicity-related deaths were noted. At 36-month median follow-up, the OS18 was 69% [95% confidence interval (CI) 60% to 80%]; the median disease-free survival and overall survival were 14.1 months (95% CI 11.0-20.1 months) and 25.4 months (95% CI 23.4-34.1 months), respectively. CONCLUSIONS: Notwithstanding promising multi-institutional efficacy results, further development of this regimen will require additional modifications to mitigate toxic effects.

Surgery alone is adequate treatment for early stage soft tissue sarcoma of the extremity.

BACKGROUND: Evolving evidence suggests that, in selected patients with tumour category 1 (T1) extremity soft tissue sarcoma (ESTS), surgery alone offers satisfactory results without decreasing survival. This study assessed the effect of sarcoma treatments on survival outcomes of T1 ESTS in a population-based data set. METHODS: Using the Surveillance, Epidemiology, and End Results database, 1618 patients with primary ESTS underwent limb-sparing surgery. Multivariable analysis was used to assess the impact of radiotherapy on overall survival (OS) and sarcoma-specific survival (SSS), adjusting for co-variables. RESULTS: Some 803 patients (49.6 per cent) underwent surgery alone for T1 ESTS. Radiotherapy in patients with low- and high-grade tumours did not result in any significant difference in OS or SSS. When stratified by grade, multivariable analysis showed that adjuvant radiotherapy was not an independent predictor of SSS (hazard ratio (HR) 1.05; P = 0.906) or OS (HR 0.89; P = 0.695) in low-grade tumours. Neither was radiotherapy a significant predictor of SSS (HR 0.87; P = 0.608) or OS (HR 0.67; P = 0.071) in high-grade tumours. CONCLUSION: This population-based appraisal validated previous evidence supporting a role for surgery alone in the treatment of T1 ESTS. Future policies should be tailored to offer patients minimal yet effective therapy, rather than maximum tolerated therapy.

Complete soft tissue sarcoma resection is a viable treatment option for select elderly patients.

BACKGROUND: Decreased performance status, comorbidities, and disease natural history may erode enthusiasm for soft tissue sarcoma (STS) resection in elderly patients. Consequently, we evaluated the outcome of elderly patients amenable to complete surgical resection treated at a single institution. METHODS: Prospectively accrued data were used to identify patients with primary STS age >or=65 years (n = 325) who underwent complete macroscopic resection at our institution (1996-2007). Univariable and multivariable analyses were performed to identify prognostic factors. RESULTS: Median age at presentation was 72 years; 179 patients (55.1%) had associated comorbidities with an ASA score of >or=3. Extremity was the most common site (57.1%; n = 186), undifferentiated pleomorphic sarcoma the most common histology (60.4%; n = 197); 232 (71.2%) were high grade, 222 (68.3%) were >5 cm. Thirty-day postoperative mortality was 0.9% (n = 3); overall complication rate was 30.7% (n = 100), and mean postoperative hospital stay was 9 days (range, 1-84). Estimated median survival was 96 months, 5-year disease-specific survival (DSS) was 63%. Multivariable analysis identified age >or=75 year (HR = 2.03), tumor size: 5-15 vs <5 cm (HR = 3.54), or >15 vs <5 cm (HR = 10.33), and high-grade (HR = 5.53) as significant independent adverse prognostic factors. Compared with patients aged 65-74 years, older patients had more high grade tumors (P = .04), received chemotherapy less often (P < .0001), developed different patterns of recurrence (P < .05), and exhibited a shorter median survival (70 months; P = .05). CONCLUSIONS: Properly selected elderly patients can safely undergo extensive STS resections. Until more effective therapies become available, surgery in the elderly is indicated and remains the best means for STS control.

Intraductal papillary mucinous neoplasms of the pancreas.

The introduction of the exocrine pancreatic classification by the World Health Organization and improvements in pancreatic imaging have led to an improved understanding of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. As a result, IPMNs of the pancreas are increasingly being recognized as a separate disease entity. IPMNs are characterized by the cystic dilatation of the pancreatic duct and its branches, with papillary projections. There are three histological subtypes of IPMNs: main duct, branch duct, and mixed. The degree of atypia ranges from adenoma to frank invasive carcinoma. The lymph nodes are involved considerably less frequently than they are in pancreatic adenocarcinoma. Most patients are symptomatic at diagnosis and require a diagnostic workup similar to that for patients with pancreatic adenocarcinoma. Although some investigators continue to advocate total pancreatectomy, the evidence in support of this is decreasing. Partial pancreatectomy remains the treatment option. Intraoperative assessment of the resection surgical margins is an important component of surgical resection. Additionally, controversy also exists regarding the nature of the follow-up and the need for adjuvant chemoradiation therapy in the patient. Unlike ductal adenocarcinomas, IPMNs follow a relatively indolent course; the 5-year survival rate in patients with invasive IPMNs is 57%. A mural nodule and a main pancreatic duct diameter greater than 5 mm have been found to be predictors of malignancy.

Surgical and endoscopic palliation for pancreatic cancer.

Patients with pancreatic cancer often present with locally advanced or metastatic disease and are deemed not to be candidates for a curative resection. Palliation in these patients focuses on relief of biliary obstruction, gastroduodenal obstruction and pain. Palliative treatment modalities include both surgical and nonsurgical approaches. Biliary obstruction is often initially treated with endoscopic biliary stenting. Two major types of biliary stents are used, plastic and metallic stents. Both of these provide similar initial relief of biliary obstruction, however, plastic stents have a greater propensity for occlusion and should primarily be used in patients with anticipated short survival duration. Metallic stents have a greater initial cost, but provide an overall cost-saving in patients with expected survival duration of over 6 months. Surgical palliation for biliary obstruction should be primarily considered in patients who fail endoscopic biliary decompression or who develop clinical evidence of gastroduodenal obstruction. In these patients, surgical palliation should consist of biliary decompression with a choledochojejunostomy when ever feasible, a gastroduodenal bypass and a chemical splanchnicectomy for pain relief. An initial prophylactic gastroenterostomy at the time of endoscopic biliary decompression is rarely indicated. The role of palliative pancreaticoduodenectomy remains controversial and to date there are no prospective randomized data to support its role in palliation of locally advanced pancreatic cancer. This review examines the available data from prospective trials for surgical and nonsurgical palliation of locally advanced and metastatic pancreatic cancer.

Pancreatic leak after left pancreatectomy is reduced following main pancreatic duct ligation.

BACKGROUND: Although much is known about the long-term outcome of patients undergoing left (distal) pancreatectomy for malignancy, comparatively little is known about the optimal management strategy for the residual transected pancreatic parenchyma and the divided pancreatic duct. Clinicopathological and operative factors that may contribute to postoperative pancreatic leak were evaluated. METHODS: A retrospective review of the medical records of 126 patients who underwent left pancreatectomy between June 1990 and December 1999 at the University of Texas M. D. Anderson Cancer Center was performed. RESULTS: Indications for left pancreatectomy included pancreatic neoplasms (n = 42; 33.3 per cent), en bloc resection for management of retroperitoneal sarcoma (n = 21; 16.7 per cent), gastric adenocarcinoma (n = 14; 11.1 per cent), renal cell carcinoma (n = 11; 8.7 per cent) and other tumours or benign conditions (n = 38; 30.2 per cent). Pancreatic parenchymal closure was accomplished by a hand-sewn technique, mechanical stapling, or a combination of the two in 83, 20 and 15 patients respectively. No form of parenchymal closure was used in eight patients. Identification of the pancreatic duct and suture ligation was performed in 73 patients (57.9 per cent). Twenty-five patients (19.8 per cent) developed a pancreatic leak. For subgroups having duct ligation or no duct ligation, pancreatic leak rates were 9.6 per cent (seven of 73 patients) and 34.0 per cent (18 of 53 patients) respectively (P < 0.001). Multivariate analysis including clinicopathological and operative factors indicated that failure to ligate the pancreatic duct was the only feature associated with an increased risk for pancreatic leak (odds ratio 5.0 (95 per cent confidence interval 2.0 to 10.0); P = 0.001). CONCLUSION: Pancreatic leak remains a common complication after left pancreatectomy. The incidence of leak is reduced significantly when the pancreatic duct is identified and directly ligated during left pancreatectomy.

Is the therapeutic index better with gemcitabine-based chemoradiation than with 5-fluorouracil-based chemoradiation in locally advanced pancreatic cancer?

PURPOSE: To retrospectively compare the toxicity and efficacy of concurrent gemcitabine-based chemoradiation with that of concurrent 5-fluorouracil (5-FU)-based chemoradiation in patients with unresectable pancreatic cancer. PATIENTS AND METHODS: Between September 1996 and May 2000, 114 patients with localized unresectable adenocarcinoma of the pancreas were treated with concurrent chemoradiation. Locally advanced unresectable disease was defined as low-density tumor in contact with the superior mesenteric artery (SMA) or celiac artery, or occlusion of the superior mesenteric-portal venous confluence. Fifty-three patients were selected to receive gemcitabine in 7 weekly cycles (250-500 mg/m(2)) with concurrent radiotherapy (median dose 30 Gy, range 30-33 Gy in 10-11 fractions). The remaining 61 patients received continuous-infusion 5-FU (200-300 mg/m(2)) with concurrent radiotherapy (30 Gy in 10 fractions). Radiotherapy was delivered to the primary tumor and regional lymphatics. Patients receiving gemcitabine and those receiving 5-FU had a similar mean Karnofsky performance status (KPS, 89% vs. 86%), distribution of tumor grade (43% vs. 33% poorly differentiated), and percent weight loss (all p = NS). However, patients treated with gemcitabine had a significantly larger median maximum cross-sectional tumor area (TA, 8.8 cm(2) vs. 5.7 cm(2), p = 0.046) and were significantly younger (median age 60 vs. 68 years, p <0.001). Severe acute toxicity (ST) was defined as toxicity requiring a hospital stay of more than 5 days, mucosal ulceration with bleeding, more than 3 dose deletions of gemcitabine or discontinuation of 5-FU, or toxicity resulting in surgical intervention or death. Kaplan-Meier analysis was used to calculate the actuarial rate of local progression on imaging (LP), the rate of distant metastasis (DM), and the overall survival (OS) rate. The imaging was reviewed in resected patients. RESULTS: Patients receiving gemcitabine developed significantly more ST during treatment (23% vs. 2%, p < 0.0001) than did those receiving 5-FU. Patients treated with gemcitabine had a similar 10-month LP rate (62% vs. 61%), 10-month DM rate (55% vs. 47%), 1-year OS rate (42% vs. 28%), and median OS duration (11 months vs. 9 months) to patients treated with 5 FU (all p = NS). Five patients who received gemcitabine and 1 patient who received 5-FU underwent margin-negative pancreaticoduodenectomy after chemoradiation. Three patients had a short segment (10 cm(2) (p = 0.03) and poor differentiation (p = 0.07) were associated with a worse survival duration; however, other factors, such as KPS and weight loss >10% and age did not influence OS. CONCLUSION: Despite the selection of healthier patients to receive gemcitabine, there was a significantly higher severe toxicity rate than with 5-FU. The median and 1-year survivals were not significantly different with the use of concurrent gemcitabine; however, the tumors treated were significantly larger. Additionally, a small number of patients with minimal arterial involvement whose disease met our radiographic definition of unresectable disease had margin-negative resections after treatment with gemcitabine-based chemoradiation. These possible benefits and the high rate of severe toxicity define a very narrow therapeutic index for concurrent gemcitabine-based chemoradiation given by this schedule of administration.