Biomedical subjects

Peter W Pisters

Publications and source records attributed to Peter W Pisters.

9 recordsLinked to original sources

PubMed2007

Management of locally recurrent soft-tissue sarcoma after prior surgery and radiation therapy.

PURPOSE: The aim of this study was to evaluate outcome and treatment toxicity after wide local re-excision (WLE), with or without additional radiation therapy, for patients with isolated first local recurrence of soft-tissue sarcoma arising within a previously irradiated field. METHODS: A retrospective review was performed of 62 consecutive patients. All patients underwent prior resection and external beam radiation. For recurrent disease, 25 patients were treated with WLE alone, and 37 patients were treated with WLE and additional radiation (45- 64 Gy). In 33 patients, the radiation was delivered via an afterloaded brachytherapy, single-plane implant. RESULTS: The 5-year disease specific and distant metastasis-free survival rates were 65% and 73%, respectively. Local control (LC) at 5 years was 51%, and on multivariate analysis, a positive surgical resection margin (p< 0.001) was associated with a lower rate of LC. Reirradiation was not associated with improved LC; however complications requiring outpatient or surgical management were more common in patients who had undergone reirradiation (80% vs. 17%, p < 0.001). Amputation was also more common in the subgroup of patients who underwent extremity reirradiation (35% with radiation vs. 11% without, p = 0.05), although only one amputation was performed to resolve a treatment complication. CONCLUSION: Conservative surgery alone results in LC in a minority of patients who have failed locally after previous excision and external beam radiation. Although selection biases and small patient numbers confound the analysis, local treatment intensification with additional radiation does not clearly improve outcome after surgical excision alone, and is associated with an increase in complications.

Aged↗

PubMed2006

Outcome of gastric cancer patients after successful gastrectomy: influence of the type of recurrence and histology on survival.

BACKGROUND: The effect of the location of disease recurrence after curative (R0) gastrectomy on patient survival has not been elucidated. The authors hypothesized that the location of recurrence would have a significant influence on survival. METHODS: Medical records of all patients who received treatment for gastric cancer at The University of Texas M. D. Anderson Cancer Center between 1985 and 1998 were reviewed. Patients who underwent R0 resection for gastric cancer and subsequently developed localized (anastomotic) recurrence (LR), lymph node (regional) recurrence (NR), or distant metastases (DM) were analyzed for overall survival (OS). All study factors were entered into a Cox proportional hazards model to provide multivariate hazard ratios. The model was adjusted for the effects of primary site of recurrence, histologic grade, patient age, and location of the primary tumor. RESULTS: This retrospective analysis included 227 consecutive patients. The median survival of patients who developed NR (11 months) was similar to that of patients who developed LR (10 months), but both groups had significantly longer median survival compared with patients who developed DM (7 months; log-rank P = .03). Patients who had well differentiated or moderately differentiated tumors had a longer OS (11 months) than patients who had poorly differentiated tumors (8 months; log-rank P = .02). In this cohort, location of the primary cancer and age at recurrence had no significant impact on OS. CONCLUSIONS: The data from this study suggested that, among patients who undergo R0 gastrectomy for gastric cancer, LR and NR versus DM should be considered a valid stratification factor for randomized trials based on significant differences in survival. Determining whether this stratification should apply to histologic differentiation will require further investigation in a larger multicenter cohort.

Female↗

PubMed2006

Surgical pathology stage by American Joint Commission on Cancer criteria predicts patient survival after preoperative chemoradiation for localized gastric carcinoma.

BACKGROUND: Preoperative chemoradiation for localized gastric cancer can modify baseline stage, as determined by surgical pathology stage. Therefore, the authors hypothesized that surgical pathology stage would be a better prognosticator of overall survival (OS) than baseline stage. METHODS: Patient populations were combined from 2 prospectively conducted, preoperative chemoradiation trials that used the same therapeutic strategy. Patients must have had localized gastric adenocarcinoma and were staged extensively, including endoscopic ultrasonography and laparoscopy. Patients had to be fit for surgery medically with a technically resectable cancer. All patients provided written informed consent. Patients first received induction chemotherapy for up to 2 months followed by chemoradiation (45 grays) and an attempted surgery. OS was correlated with pretreatment and posttreatment parameters, including surgical pathology stage according to American Joint Commission on Cancer criteria. RESULTS: Of 74 patients who were registered, 69 patients (93%) had undergone surgery. Nineteen patients (26%) had a pathologic complete response (pathCR), and 55 patients (81%) had a curative (R0) resection. None of the pretreatment parameters correlated with OS; however, longer OS correlated with lower pathologic stage (P < .0001), R0 resection (P < .001), clinical response noted prior to surgery (P = .002), pathCR (P = .004), lower pathologic lymph node classification (P = .006), and lower pathologic tumor classification (P = .03). Pathologic stage and R0 resection were independent prognostic factors for OS (multivariate Cox model; both P = .05). CONCLUSIONS: When preoperative chemoradiation strategy was employed for gastric cancer, the surgical pathology stage, a reflection of cancer's biologic heterogeneity, was a better prognosticator of OS than the baseline clinical stage. Surgical pathology stage, in this setting, may serve as an intermediate endpoint for Phase II/III trials.

Adult↗

PubMed2005

Polymorphisms of cytochrome P4501A2 and N-acetyltransferase genes, smoking, and risk of pancreatic cancer.

To test the hypothesis that genetic variation in the metabolism of tobacco carcinogens, such as aromatic amines (AA) and heterocyclic amines (HCA), contributes to pancreatic cancer, we have examined genetic polymorphisms of three key enzymes, i.e. cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase 1 and 2 (NAT1 and NAT2), in a hospital-based case-control study of 365 patients with pancreatic adenocarcinoma and 379 frequency-matched healthy controls. Genotypes were determined using PCR-restriction fragment length polymorphism (RFLP) and Taqman methods. Smoking information was collected by personal interview. Adjusted odds ratio (AOR) and 95% confidence interval (CI) was estimated by unconditional multivariate logistic regression analysis. We found that the NAT1 'rapid' alleles were associated with a 1.5-fold increased risk of pancreatic cancer (95% CI: 1.0-2.1) with adjustment of potential confounders. This effect was more prominent among never smokers (AOR: 2.4, 95% CI: 1.4-4.3) and females (AOR: 1.8, 95% CI: 1.0-3.1). Some genotypes were significantly associated with increased risk for pancreatic cancer among smokers, especially heavy smokers (<20 pack years). For example, heavy smokers with the CYP1A2*1D (T-2467delT) delT, CYP1A2*1F(A-163C) C allele, NAT1 'rapid' or NAT2 'slow' alleles had an AOR (95% CI) of 1.4 (0.7-2.3), 1.9 (1.1-3.4), 3.0 (1.6-5.4) and 1.5 (0.8-2.6), respectively, compared with never smokers carrying the non-at-risk alleles. These effects were more prominent in females than in males. The corresponding AOR (95% CI) was 3.1 (1.0-8.0), 3.8 (1.5-10.1), 4.5 (1.6-12.7) and 2.0 (0.8-5.1) for females versus 1.0 (0.4-1.9), 1.1 (0.5-2.4), 2.1 (1.0-4.6) and 1.1 (0.5-2.6) for males. A significant synergistic effect of CYP1A2*1F C allele and NAT1"rapid" alleles on the risk for pancreatic cancer was also detected among never smokers (AOR: 2.9, 95% CI: 1.2-6.9) and among females (AOR: 2.5, 95% CI: 1.1-5.7). These data suggest that polymorphisms of the CYP1A2 and NAT1 genes modify the risk of pancreatic cancer.

Adenocarcinoma↗

PubMed2005

5,10-Methylenetetrahydrofolate reductase polymorphisms and the risk of pancreatic cancer.

To test the hypothesis that 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms modify the risk of pancreatic cancer, we conducted a hospital-based, case-control study involving 347 patients with newly diagnosed pancreatic adenocarcinoma and 348 healthy controls, frequency matched by age, sex, and race. MTHFR polymorphisms were determined using the PCR-RFLP method. Association of these polymorphisms with the risk of pancreatic cancer was estimated by unconditional logistic regression analysis. We found that the C667T (but not the A1298C) polymorphism had a significant main effect on the risk of pancreatic cancer. The frequencies of the MTHFR 667CC, 667CT, and 667TT genotypes were 49.5%, 38.6%, and 11.9%, respectively, among cases compared with 48.5%, 45.0%, and 6.5%, respectively, among controls. Individuals with the 667TT genotype displayed a 2-fold increased risk for pancreatic cancer compared with those with the CC/CT genotypes [adjusted odds ratio (OR), 2.14; 95% confidence interval (95% CI), 1.14-4.01]. Multivariate analyses found that the effect of the 677TT genotype on the risk of pancreatic cancer was present among ever smokers (OR, 5.53; 95% CI, 2.0-15.3) and ever alcohol drinkers (OR, 3.16; 95% CI, 1.30-7.69) but not in never smokers (OR, 0.82; 95% CI, 0.33-2.06) and never drinkers (OR, 1.42; 95% CI, 0.56-3.62). Furthermore, a positive interaction between the MTHFR TT genotype and heavy smoking or heavy alcohol consumption was detected. The OR (95% CI) of pancreatic cancer was 6.83 (1.91-24.38) for heavy smokers among the TT carriers compared with never smokers with the CC/CT genotypes and 4.23 (0.88-20.3) for heavy drinkers with the TT genotype compared with nondrinkers with the CC/CT genotypes. These observations support a role for folate metabolism in pancreatic cancer, especially among smokers and heavy drinkers.

Adenocarcinoma↗

PubMed2003

Combined-modality treatment of localized soft tissue sarcomas of the extremities.

Over the past 20 years, considerable progress has been made in the treatment of patients with extremity soft tissue sarcomas. There has been a migration away from amputation toward treatment by excision plus radiation for most patients with localized tumors. Decisions about the optimal use and sequencing of surgery and radiation remain complex. Whereas it is clear that local control is probably not impacted significantly by the treatment sequence, rates of wound complication, fibrosis, and edema are affected by the treatment sequence. In addition, recent single-institution reports indicate that some carefully selected patients can be treated by surgery alone. The recent data evaluating treatment by surgery alone and treatment sequencing variables do not lead to a situation in which clear, uniform recommendations for treatment can be made for many patients with extremity soft tissue sarcomas. Indeed, treatment planning for patients with extremity soft tissue sarcoma in the new millennium is infinitely more complex than it was in the era when amputation was the primary treatment for these patients. Considerable clinical experience and multidisciplinary input are required for optimal treatment planning for these patients. Future research should be directed at refining the indications for specific therapies, reducing the toxicities of local therapies, and developing more effective systemic therapies.

Chemotherapy, Adjuvant↗

PubMed2003

Staging and prognostic factor evaluation in soft tissue sarcoma.

Over the past decade, there has been significant emphasis on the elucidation of clinicopathologic prognostic factors in STS. This has allowed for identification of the "high-risk" patient at presentation. Molecular factors may further refine the identification of high-risk patients. Setting-related prognostic factors are often amenable to change, and all STS patients should probably be referred for specialty consultation before treatment so that they can benefit from optimal diagnostic, therapeutic, and multidisciplinary approaches. The ongoing pursuit of prognostic issues should also recognize the dynamic nature of prognosis course in a patient's disease.

Clinical Trials as Topic↗

PubMed2003

Administration of optimal biological dose and schedule of interferon alpha combined with gemcitabine induces apoptosis in tumor-associated endothelial cells and reduces growth of human pancreatic carcinoma implanted orthotopically in nude mice.

PURPOSE: We determined whether chronic administration of IFN-alpha at optimal biological dose inhibits angiogenesis of human pancreatic carcinoma growing in the pancreas of nude mice. EXPERIMENTAL DESIGN: Cells of the human pancreatic cancer cell line L3.6pl were implanted into the pancreas of nude mice. Seven days later, groups of mice received s.c. injection with IFN-alpha alone (50,000 units biweekly or 10,000 units daily), i.p. injection with gemcitabine alone (125 mg/kg biweekly), or injection with both daily IFN-alpha and biweekly gemcitabine for 35 days. In a survival study, the mice were treated until they became moribund. RESULTS: Biweekly treatments with 50,000 units of IFN-alpha alone were ineffective. In contrast, daily injections of IFN-alpha (10,000 units/day) alone, biweekly injections of gemcitabine alone, or the combination of IFN-alpha and gemcitabine reduced tumor volume by 53%, 70%, and 87%, respectively. Immunohistochemical analysis revealed that treatment with IFN-alpha alone or with IFN-alpha plus gemcitabine inhibited expression of the proangiogenic molecules basic fibroblast growth factor and matrix metalloproteinase 9 more than did treatment with gemcitabine alone. These treatments also decreased the staining of proliferating cell nuclear antigen within the tumor and induced apoptosis in tumor-associated mouse endothelial cells (staining with CD31/terminal deoxynucleotidyl transferase-mediated nick end labeling), leading to a decrease in microvessel density. CONCLUSIONS: These data show that administration of IFN-alpha at optimal biological dose and schedule in combination with gemcitabine induced apoptosis in tumor-associated endothelial cells and decreased growth of human pancreatic cancer cells in the pancreas, leading to a significant increase in survival.

Animals↗

PubMed2002

Irinotecan/cisplatin in advanced, treated gastric or gastroesophageal junction carcinoma.

We conducted a phase II study to assess the response rate and toxicity profile of the irinotecan (CPT-11, Camptosar) plus cisplatin combination administered weekly to patients with at least one previous chemotherapy for advanced adenocarcinoma of the stomach or gastroesophageal junction. Patients with histologic proof of adenocarcinoma of the stomach orgastroesophageal junction with adequate liver, kidney, and bone marrow functions were treated with 50 mg/m2 of irinotecan plus 30 mg/m2 of cisplatin, both administered intravenously 1 day a week for 4 consecutive weeks, followed by a 2-week recovery period. Response rate, time to disease progression, survival, and toxic effects were analyzed. Of 32 registered patients, 29 were assessable. Nine patients (31%) achieved a partial response. Median time to disease progression was 7 weeks (range: 5-48+ weeks) and median survival time was 5 months (range: 2.5-31 months). There were no treatment-related deaths. Major toxic effects included diarrhea, neutropenia, and fatigue. Of 260 doses administered in 65 6-week courses, 46 doses were either delayed or missed. Most delayed or missed doses occurred in the third or fourth week of the cycle. We concluded that the combination of irinotecan and cisplatin is an active second-line therapy for patients with advanced gastric or gastroesophageal adenocarcinoma in whom one previous chemotherapy has failed. Modifications in doses and schedule are warranted to increase the tolerability of the regimen. Phase III trials are necessary to establish the clinical utility of irinotecan/cisplatin in these patient populations.

Adenocarcinoma↗