Judy L. Smith

Predictive factors associated with long-term survival in patients with neuroendocrine tumors of the pancreas

BackgroundNeuroendocrine tumors of the pancreas are rare tumors. We identified predictive factors that are associated with long-term survival (≥5 years).MethodsFifty patients with a diagnosis of neuroendocrine tumors of the pancreas were retrospectively evaluated. The following factors were evaluated for disease-specific mortality: age, sex, primary tumor location, functional status, type of primary tumor treatment, presence or absence of liver metastases, timing of liver metastases occurrence, and type of liver metastases treatment. Aggressive treatment of the liver metastases included surgery, chemoembolization, or intrahepatic arterial infusion chemotherapy.ResultsTwenty-three patients (47%) had tumor located in the head of the pancreas, and 29 patients (58%) had nonfunctioning tumor. Thirty-nine patients (78%) had liver metastases. The median follow-up for the entire group was 35 months (range, 76–206 months). The median survival for the entire group was 40 months, and the overall 1-, 2-, and 5-year survival rates were 84%, 69%, and 36%, respectively. Factors that had a significant favorable effect on survival included curative resection of the primary tumor, metachronous liver metastases, absence of liver metastases, and aggressive treatment of the liver metastases.ConclusionsDefinitive surgical resection of the primary tumor, absence of liver metastases, metachronous liver metastases, and aggressive treatment of the liver metastases were predictors of long-term survival in patients with neuroendocrine tumors of the pancreas.

Oxaliplatin in Combination With Protracted-Infusion Fluorouracil and Radiation: Report of a Clinical Trial for Patients With Esophageal Cancer

PURPOSE To identify a dose and schedule of oxaliplatin (OXP) to be safely administered in combination with protracted-infusion (PI) fluorouracil (5-FU) and external-beam radiation therapy (XRT) for patients with primary esophageal carcinoma (EC). PATIENTS AND METHODS Eligibility included therapeutically naïve EC patients with clinical disease stages II, III, or IV. Initial doses and schedules for cycle 1 consisted of OXP 85 mg/m(2) on days 1, 15, and 29; PI 5-FU 180 mg/m(2) for 24 hours for 35 days; and XRT 1.8 Gy in 28 fractions starting on day 8. At completion of cycle 1, eligible patients could undergo an operation or begin cycle 2 without XRT. Postoperative patients were eligible for cycle 2. Stage IV patients were allowed three cycles in the absence of disease progression. OXP and 5-FU increases were based on dose-limiting toxicity (DLT) encountered in cohorts of three consecutive patients. RESULTS Thirty-eight eligible patients received therapy: 22 noninvasively staged as IV and 16 noninvasively staged as II and III. Thirty-six patients completed cycle 1, 29 patients started cycle 2, and 24 patients completed cycle 2. The combined-modality therapy was well tolerated, but DLT prevented OXP and 5-FU escalation. No grade 4 hematologic toxicity was noted. Eleven grade 3 and two grade 4 clinical toxicities were noted in eight patients. After cycle 1, 29 patients (81%) had no cancer in the esophageal mucosa. Thirteen patients underwent an operation with intent to resect the esophagus; five patients (38%) exhibited pathologic complete responses. CONCLUSION OXP 85 mg/m(2) on days 1, 15, and 29 administered with PI 5-FU and XRT is safe, tolerable, and seems effective against primary EC. The role of OXP in multimodality regimens against EC deserves further evaluation.

Esophageal resection for carcinoma in patients older than 70 years.

BackgroundA larger number of older patients are presenting as candidates for esophageal resection. An aggressive surgical approach in this population is controversial.MethodsFour hundred thirteen patients with esophageal cancer who presented to Roswell Park Cancer Institute from 1991 to 1998 were retrospectively reviewed. Clinical data, perioperative details, and postoperative courses were compared for patients older and younger than 70 years.ResultsOne hundred forty-seven patients (36%) were older than 70 years. Risk factors, clinical symptoms, histology, and stage at presentation were equivalent for both age groups. A higher percentage of patients <70 years were candidates for curative resection. There were no significant differences between groups for estimated blood loss, intraoperative transfusions, length of stay, overall morbidity, or mortality. Only postoperative myocardial infarction and atrial fibrillation were increased in the older group. Excluding stage IV disease, there was a significant and similar improvement in median survival after resection for patients both <70 years and >70 years.ConclusionsIn conclusion, esophageal cancer in older patients warrants surgical resection because the benefit to the patient is the same as it is for younger patients, without a significant increase in operative morbidity or mortality.

Postoperative complications after splenectomy for hematologic malignancies

OBJECTIVE The authors analyzed the frequency and character of postoperative complications after splenectomy in patients with hematologic malignancies, and correlated these findings with preoperative conditions that could have predicted their outcome. SUMMARY BACKGROUND DATA Splenectomy is performed for hematologic malignancies for diagnostic and therapeutic indications. The role of splenectomy for lymphoproliferative and myeloproliferative malignancies is complex and sometimes controversial. METHODS The medical records of 135 patients undergoing splenectomies for hematologic malignancies at Roswell Park Cancer Institute from January 1, 1984 to December 31, 1993 were reviewed retrospectively. These included Hodgkins disease (HD), hairy cell leukemia (HCL), non-Hodgkins lymphoma (NHL), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), and a miscellaneous group. RESULTS The overall postoperative complication and mortality rates for all patients were 52% and 9%, respectively. The complication rate was 63% for patients whose spleens weighed greater than 2000 g, and 29% for patients whose spleens weighed less than 2000 g (p = 0.001). Seventy-three percent of the postoperative deaths were due to septic complications, only one of which was caused by an encapsulated organism. Complications occurred in less than 20% of patients with the diagnosis of HD and HCL; more than 50% of patients with NHL, CLL, and CML suffered postoperative complications. CONCLUSIONS Splenectomy performed in patients with hematologic malignancies is a potentially morbid procedure. Splenic size was the only preoperative factor found to be predictive of postoperative complications. The complication rate differed significantly between the different diagnostic subgroups.

Concomitant chemotherapy and reirradiation as management for recurrent cancer of the head and neck.

Thirty-five patients with inoperable recurrent head and neck cancer previously treated with definitive irradiation were treated with reirradiation and concomitant chemotherapy. Patient records were retrospectively reviewed to assess toxicity, response, and survival. Patients received one of three regimens: 1) 40 Gy total (2 Gy daily), 300 mg/m2 5-fluorouracil intravenous bolus, and 2 g hydroxyurea orally daily for 5 days; 2) 48 Gy total (1.2 Gy twice daily), 300 mg/m2 5-fluorouracil intravenous bolus, and 1.5 g hydroxyurea orally daily for 5 days; 3) 60 Gy total (1.5 Gy twice daily), 300 mg/m2 5-fluorouracil intravenous bolus, and 1.5 g hydroxyurea orally daily for 5 days. For all regimens, treatment was given only on weeks 1, 3, 5, and 7. Acute toxicity was mainly hematologic and was less severe with the lower hydroxyurea dose. Acute mucosal and skin toxicity was acceptable for all regimens. Late toxicity was noted in 4 of 17 patients who survived 12 months or more. Late effects were Radiation Therapy Oncology Group grade 3 or less. Fifteen of 35 patients achieved a complete response, and 11 of 35 patients achieved a partial response. The median survival rate was 10.5 months. There was no significant difference in responses or median survival between the groups. Reirradiation of head and neck cancer with 5-fluorouracil and hydroxyurea offers acceptable acute toxicity and minimal late effects. The clinical response rates and median survival are encouraging. Further investigation is warranted.

NATIONAL CANCER INSTITUTE (PHASE II) STUDY OF HIGH-GRADE GLIOMA TREATED WITH ACCELERATED HYPERFRACTIONATED RADIATION AND IODODEOXYURIDINE: RESULTS IN ANAPLASTIC ASTROCYTOMA

PURPOSE We report the outcome of a Phase II study of a cohort of patients with high-grade glioma treated with accelerated hyperfractionated radiation and the radiation sensitizer, iododeoxyuridine (IdUrd). METHODS AND MATERIALS Between January 1988 and December 1990, 39 consecutive patients with high-grade glioma were enrolled and treated on a Phase II protocol including hyperfractionated radiation and IdUrd. Thirty-two patients were male and seven were female. Age range was 19 to 71 years with a median age of 38 years. IdUrd (1000 mg/m2 per day) was administered in two separate 14-day courses, the first during the initial radiation field and the second during the final cone-down field. All patients were treated consistently with partial brain technique and received 1.5 Gy/fraction twice daily to a mean total dose of 71.25 Gy (range 66-72 Gy excluding one patient who did not complete treatment). The initial field was treated to 45 Gy followed by a cone-down field covering the tumor volume plus a 1-cm margin to the final dose. Patients were assessed for acute and long-term morbidity and followed for outcome. Two patients had biopsies during the course of treatment. Flow cytometry and high performance liquid chromatography was used to evaluate the labeling index and the percent replacement of IdUrd in the biopsy specimen. RESULTS Thirty-eight of 39 patients completed therapy. One patient died on treatment at 48 Gy and is included in the survival analysis. No patient was lost to follow-up. Twenty-one patients had Grade 3 (anaplastic astrocytoma) tumors and 18 patients had Grade 4 (glioblastoma multiforme). Median survival for the entire cohort was 23 months. For the glioblastoma multiforme patients, median survival was 15 months. The median survival of the anaplastic astrocytoma patients has not yet been reached. In the patients assessed, the range of IdUrd tumor cell incorporation was only 0-2.4%. CONCLUSION Accelerated hyperfractionated radiation therapy with IdUrd was administered with acceptable acute toxicity. The major acute side effects of mucositis and thrombocytopenia were related to IdUrd infusion and were dose-dependent. There were no unacceptable acute toxicities referable to the radiation as delivered. With a median potential follow-up of 51 months, the actuarial median survival of the glioblastoma multiforme patients is comparable with the best previously published reports. The outcome of patients with anaplastic astrocytoma compares very favorably with even the most aggressive multi-modality approaches in the recent literature with a minimum of acute morbidity.

The introducer technique is the optimal method for placing percutaneous endoscopic gastrostomy tubes in head and neck cancer patients

BackgroundPercutaneous endoscopic gastrostomy (PEG) tubes are often placed in head and neck cancer patients to provide nutritional support, but studies have found the complication rates to be higher than other subsets of patients who undergo PEG placement. Complication rates as high as 50% have been reported, with the bulk of these complications being PEG site issues (i.e., cellulitis, abscess, fascitis, and tumor implantation). Because the pull technique has been the primary technique used, the theory is that the transoral tube passage is the source of the complications in these patients. Alternatively, the introducer technique uses a transabdominal approach to place the device, avoiding any tube contamination by upper aerodigestive organisms or tumor cells. At our institution, this technique has been used exclusively for head and neck cancer patients and this article reports our experience.MethodsOne hundred forty-nine head and neck cancer patients who had a prophylactic PEG tube placed were reviewed from January 1, 1999 to December 31, 2003. The rates of placement success, morbidity, and complications were determined.ResultsSuccessful placement was achieved in 148 (99%) patients without any PEG-related deaths. Overall, 17 complications (11%) occurred, with only one major complication (0.7%) identified. PEG site infections were uncommon with only five cases (3.4%) and all were mild cellulitis.ConclusionsThe introducer technique is the safest method for PEG tube placement in head and neck cancer patients. The overall rate of complications is low and PEG site infectious complications are rare. The introducer technique should be the method of choice for PEG tubes in head and neck cancer patients.

Chemotherapy-Induced Carcinoembryonic Antigen Surge in Patients with Metastatic Colorectal Cancer

Objectives: To investigate the incidence of carcinoembryonic antigen (CEA) surge in patients with metastatic colorectal cancer (MCRC) and its implications on clinical outcome. Methods: A retrospective chart review of patients with MCRC treated with chemotherapy at Roswell Park Cancer Institute from January 2000 to May 2004 was conducted. A CEA surge was defined as an increase of >20% from baseline followed by a >20% drop in one or more subsequent CEA levels compared to baseline. The incidence of CEA surge and its association with clinical outcome was investigated. Results: Eighty-nine patients were evaluable for CEA surge. A CEA surge was documented in 10 patients. The CEA surge lasted <4 months in all 10 patients and was associated with a clinical benefit. No significant correlation was noted between CEA surge and site of primary tumor, site of metastatic disease, or tumor differentiation. Conclusions: CEA surges can be observed in patients receiving chemotherapy for MCRC and are often associated with a clinical benefit. None of the CEA surges satisfied the American Society of Clinical Oncology definition of CEA progression. A rise in CEA after initiation of chemotherapy, unless lasting >4 months, cannot be used as an indicator of progressive disease.

High-grade dysplasia within Barrett's esophagus: Controversies regarding clinical opinions and approaches

Barretts esophagus with high-grade dysplasia is a well-known risk factor for the development of esophageal adenocarcinoma, which has become the predominant form of esophageal cancer in the United States. This review addresses four major fundamental issues that shape our treatment decisions regarding high-grade dysplasia within Barretts esophagus: (1) the poorly defined natural history of high-grade dysplasia in its progression to adenocarcinoma, (2) the potentially high morbidity and mortality of esophageal resection for high-grade dysplasia, (3) the difficulty in detecting cancer among dysplastic cells during endoscopy, and (4) the controversial role of endoscopic mucosal ablative therapy for high-grade dysplasia. Until there are more accurate surveillance methods, better biochemical or molecular markers in predicting cancerous progression, or more effective minimally invasive methods of treatment, esophagogastrectomy must be considered the standard means of managing patients with Barretts esophagus and high-grade dysplasia. Regular rigorous systematic surveillance and endoscopic mucosal ablation are alternative treatment options that are available but should be used only under strict conditions. The decision to proceed in a certain direction is quite complex and challenging and ideally requires the feedback of patients who are properly educated about the controversies surrounding this disease.

Is Glucagonoma of the Pancreas a Curable Disease

AbstractBackground. Glucagonomas are rare neuroendocrine tumors of the pancreas. Because of its rarity, its natural history is not well understood. Aim. We evaluated the natural history of glucagonomas treated at a teritary care cancer center. Methods. A retrospective analysis of 12 patients during 1970 to 2000 was performed. Six patients (50%) had a tumor located in the head of the pancreas. Results. Abdominal pain (83%) and weight loss (75%) were the most common symptoms. Median tumor size was 6 cm (range 0.04–10). Seven patients (58%) had liver metastases. Five patients (42%) underwent curative resection. Overall median survival was 66 mo, and 5-yr overall survival was 66%. Five-yr overall survival was 83% for patients who had resection versus 50% for the non-resected patients (p=0.04). Patients who were disease-free had a complete resection of the primary tumor and no liver involvement. Conclusions. Glucagonomas generally present with liver metastases at the time of diagnosis. Cure is only possible if the disease is localized and completely resected.