Biomedical subjects

J E Tepper

Publications and source records attributed to J E Tepper.

At least 19 recordsLinked to original sources

PubMed1997

Induction chemoradiotherapy followed by esophagectomy in patients with carcinoma of the esophagus.

BACKGROUND: Induction chemoradiotherapy followed by esophagectomy may provide results superior to those of single-modality treatment in patients with esophageal cancer. The purpose of this study was to review our experience with this approach for esophageal cancer. METHODS: From 1988 to 1996, 166 consecutive patients with esophageal cancer were evaluated; 66 entered a protocol of chemotherapy (5-fluorouracil, cisplatin) concurrent with radiation (45 Gy) followed by esophagectomy. Fifty-four patients completed the protocol. RESULTS: Toxicity associated with induction chemoradiotherapy was minimal. The actuarial survival at 12, 24, and 36 months was 59%, 42%, and 32%, respectively. The pathologic complete response (pCR) rate was 41%, with 12-, 24-, and 36-month survivals of 77%, 50%, and 45%, whereas non-pCR patients had survivals of 46%, 35%, and 23%. The difference in survival between pCR and non-pCR patients was not significant (p = 0.13), but the difference in recurrence-free survival was significant (p = 0.007). CONCLUSIONS: This well-tolerated protocol resulted in a high pCR. Trimodality treatment for esophageal cancer may provide long-term survival in some patients regardless of their pCR status.

Adenocarcinoma↗

PubMed1997

Adjuvant postoperative fluorouracil-modulated chemotherapy combined with pelvic radiation therapy for rectal cancer: initial results of intergroup 0114.

PURPOSE: The combination of radiation therapy with fluorouracil (5-FU)-based chemotherapy is generally accepted as appropriate postoperative therapy for patients with adenocarcinomas of the rectum that extend through the bowel wall or with lymph nodes positive for tumor. We attempted to determine whether the efficacy of this postoperative therapy could be improved by the addition of leucovorin and/or levamisole. METHODS: A total of 1,696 patients were randomized and eligible for treatment with one of four treatment schemes. All patients received two cycles of bolus 5-FU-based systemic chemotherapy followed by pelvic radiation therapy with chemotherapy and two more cycles of the same systemic chemotherapy. Chemotherapy was either 5-FU alone, 5-FU with leucovorin, 5-FU with levamisole, or 5-FU with leucovorin and levamisole. RESULTS: With a median follow-up duration of 48 months, there is no statistically significant advantage to any of the treatment regimens compared with bolus 5-FU alone. There is evidence of increased gastrointestinal toxicity with the three-drug combination compared with bolus 5-FU alone. Statistical analysis suggests it is very unlikely that either levamisole-containing combination will be shown to be of value with further follow-up evaluation. CONCLUSION: There is no evidence at present for a beneficial effect of levamisole in the adjuvant treatment of rectal cancer. Definitive evaluation of the effect of the addition of leucovorin to 5-FU and pelvic radiation will require further follow-up evaluation.

Adenocarcinoma↗

PubMed1996

Tumor retention of 5-fluorouracil following irradiation observed using 19F nuclear magnetic resonance spectroscopy.

PURPOSE: The combination of 5-fluorouracil (5FU) and radiation results in improved tumor control in a variety of gastrointestinal cancers. We propose the enhancement is related to radiation potentiating the antitumor effects of 5FU. To better understand the mechanism of the 5FU-radiation interaction, 19F nuclear magnetic resonance (NMR) spectroscopy experiments were performed to observed the tumor clearance and metabolism of 5FU. METHODS AND MATERIALS: Experiments were performed on 10 3-6-week-old female (Nu/Nu) athymic nude mice. Flank tumors measuring approximately 1.0 cm in diameter 3 weeks following a subcutaneous injection of 1 x 10(6) human colon adenocarcinoma (HT-29) cells were studied. In our first group, all animals received an intravenous bolus injection of 5FU (100 mg/kg) immediately before spectroscopic analysis. Animals in the second group were first treated with a single tumor radiation dose of 10 Gy just before the 5FU injection and subsequent spectroscopy. Spectroscopic analysis was performed with a 2.0-T NMR spectroscopy system. RESULTS: The tumor retention of 5FU was prolonged in animals receiving radiation before the drug infusion. The tumor clearance rate of the 5FU for nonirradiated animals was 0.0178 +/- 0.0082/min vs. 0.0055 +/- 0.0027/min for irradiated animals, reflecting a threefold reduction in drug clearance in the irradiated tumors. The difference was significant at p < 0.005. CONCLUSION: Our preliminary experiments suggest the enhanced cytotoxicity seen with concurrent 5FU and radiation is related to prolonged tumor retention of 5FU induced by radiation. This is consistent with the hypothesis that radiation is potentiating the cytotoxic effects of 5FU.

Animals↗

PubMed1996

Concurrent radiation therapy and chemotherapy followed by esophagectomy for localized esophageal carcinoma.

PURPOSE: A prospective study was performed to determine the outcome of patients with esophageal cancer who received preoperative radiation therapy and chemotherapy followed by esophagectomy, and to determine the role of preresection esophagogastroduodenoscopy (EGD) in predicting the patients in whom surgery could possibly be omitted, and the impact of surgery on survival. MATERIALS AND METHODS: Thirty-five patients with localized carcinoma of the esophagus received concurrent external-beam radiotherapy and chemotherapy followed by esophagectomy. Patients received 45 Gy in 25 fractions. Chemotherapy consisted of continuous infusion fluorouracil (5-FU; 1,000 mg/m2/d) on days 1 through 4 and 29 through 32 and cisplatin (100 mg/m2) on day 1. Patients underwent an Ivor-Lewis esophagectomy 18 to 33 days after completion of radiotherapy. RESULTS: Eighty percent of the patients had squamous cell carcinoma and 20% had adenocarcinoma. In addition, 51% had a pathologic complete response (CR). Twenty-two of the 35 underwent a preresection EGD before resection. Seventeen of the 22 (77%) had negative pathology from the preresection EGD, but seven of the 17 (41%) had residual tumor at surgery. The median survival and disease-free survival rates for all patients were 25.8 months and 32.8 months, respectively. Eighteen patients (51%) had no tumor at resection. The median survival for these patients was 36.8 months; the median disease-free survival time has not been reached. The median survival and disease-free survival rate for the patients with residual tumor in the surgical specimen were 12.9 months and 10.8 months, respectively. CONCLUSION: Preresection EGD is not reliable for determining the presence of residual disease or the patients in whom surgery could be omitted. Twenty-five percent of the patients with residual tumor in the resected surgical specimen were long-term survivors; this suggests a benefit from esophagectomy after concurrent radiotherapy and chemotherapy.

Adenocarcinoma↗

PubMed1996

Treatment of pancreatic cancer: current limitations, future possibilities.

In an attempt to improve the grave prognosis associated with the diagnosis of pancreatic cancer, researchers have explored a number of novel therapies. These include hormonal therapy, immunotherapy, radiopharmaceuticals, and novel chemotherapeutic agents. Unfortunately, most of these efforts have led at best to modest improvements in median survival, and have provided little opportunity for cure. Recent advances at the molecular level may provide an alternative approach to the management of pancreatic cancer. The majority of pancreatic cancers possess K-ras mutations. K-ras proteins are small (21-kd) proteins that normally serve as guanosine triphosphate (GTP)-regulated switches to control a diverse array of cellular signals that modulate highly regulated programs of proliferation, differentiation, and death. Newer therapies aimed at modifying the ras signal transduction pathways may provide avenues for future clinical investigation.

Forecasting↗

PubMed1996

Role of radiation therapy in retroperitoneal sarcomas.

Historically, patients with retroperitoneal sarcomas have had a poor prognosis. Surgical resection continues to be the standard treatment for these tumors. However, their anatomic location and large size at presentation often make complete surgical resection infeasible. Even with complete gross removal of tumor, most patients will experience local failure. Adjuvant radiation therapy has been used to improve local control rates. In the postoperative setting, radiation doses to the tumor bed are limited by radiation tolerances of surrounding normal tissues. Extrapolation of data from soft-tissue sarcomas at other sites suggests that delivery of higher radiation doses, in combination with surgery, may favorably affect local control. Preoperative radiation therapy, in combination with brachytherapy or intraoperative radiation therapy at the time of surgical resection, allows for the safe delivery of higher doses of radiation than is possible in the postoperative setting. These approaches make it possible to maximize the likelihood of local control and cure while minimizing normal tissue toxicity.

Antineoplastic Agents↗

PubMed1995

A portable software tool for computing digitally reconstructed radiographs.

PURPOSE: To develop a portable software tool for fast computation of digitally reconstructed radiographs (DRR) with a friendly user interface and versatile image format and display options. To provide a means for interfacing with commercial and custom three-dimensional (3D) treatment planning systems. To make the tool freely available to the Radiation Oncology community. METHODS AND MATERIALS: A computer program for computing DRRs was enhanced with new features and rewritten to increase computational efficiency. A graphical user interface was added to improve ease of data input and DRR display. Installer, programmer, and user manuals were written, and installation test data sets were developed. The code conforms to the specifications of the Cooperative Working Group (CWG) of the National Cancer Institute (NCI) Contract on Radiotherapy Treatment Planning Tools. RESULTS: The interface allows the user to select DRR input data and image formats primarily by point-and-click mouse operations. Digitally reconstructed radiograph formats are predefined by configuration files that specify 19 calculation parameters. Enhancements include improved contrast resolution for visualizing surgical clips, an extended source model to stimulate the penumbra region in a computed port film, and the ability to easily modify the CT numbers of objects contoured on the planning computed tomography (CT) scans. CONCLUSIONS: The DRR tool can be used with 3D planning systems that lack this functionality, or perhaps improve the quality and functionality of existing DRR software. The tool can be interfaced to 3D planning systems that run on most modern graphics workstations, and can also function as a stand-alone program.

Radiographic Image Enhancement↗

PubMed1995

Radiation therapy quality control in a clinical trial of adjuvant postoperative treatment for rectal cancer.

PURPOSE: Deviations from protocol can detract from the reliability of results obtained in prospective clinical trials. In an effort to decrease the number of deviations in a prospective trial of adjuvant treatment for rectal cancer, we undertook pretreatment review of the irradiated fields. METHODS AND MATERIALS: Before initiation of radiation therapy, patients' radiation therapy fields were simulated by their radiation oncologists and films were submitted for review. The treating physicians were then informed whether their fields were in compliance with the protocol or whether any modifications were needed. RESULTS: Among the 625 patients participating in this study who received radiation therapy as a component of protocol treatment, 419 (67%) had no radiation therapy deviations, 127 (20%) had minor deviations, and 51 (8%) had major deviations; 28 (4%) could not be evaluated or did not receive protocol treatment because of circumstances beyond the treating radiation oncologist's control. The pretreatment quality control review identified major deviations in the radiation portals for 57 cases; these findings were communicated to the radiation oncologists prior to initiation of treatment, and, on final review, 40 had no deviation or only minor deviation. CONCLUSION: In the absence of pretreatment quality control review, 40 additional patients would have had major deviations from their radiation therapy protocol. On the basis of these findings, it is estimated that pretreatment quality control reduced the rate of major deviation from 15% to 8%. Pretreatment review of radiation therapy parameters is an effective method of reducing the frequency of major deviations in prospective clinical trials.

Clinical Protocols↗

PubMed1995

Late effects of radiation therapy on the gastrointestinal tract.

Late gastrointestinal complications of radiation therapy have been recognized but not extensively studied. In this paper, the late effects of radiation on three gastrointestinal sites, the esophagus, the stomach, and the bowel, are described. Esophageal dysmotility and benign stricture following esophageal irradiation are predominantly a result of damage to the esophageal wall, although mucosal ulcerations also may persist following high-dose radiation. The major late morbidity following gastric irradiation is gastric ulceration caused by mucosal destruction. Late radiation injury to the bowel, which may result in bleeding, frequency, fistula formation, and, particularly in small bowel, obstruction, is caused by damage to the entire thickness of the bowel wall, and predisposing factors have been identified. For each site a description of the pathogenesis, clinical findings, and present management is offered. Simple and reproducible endpoint scales for late toxicity measurement were developed and are presented for each of the three gastrointestinal organs. Factors important in analyzing late complications and future considerations in evaluation and management of radiation-related gastrointestinal injury are discussed.

Dose-Response Relationship, Radiation↗

PubMed1994

Late effects of intraoperative radiation therapy on retroperitoneal tissues, intestine, and bile duct in a large animal model.

PURPOSE: The late histopathological effects of intraoperative radiotherapy (IORT) on retroperitoneal tissues, intestine, and bile duct were investigated in dogs. METHODS AND MATERIALS: Fourteen adult foxhounds were subjected to laparotomy and varying doses (0-45 Gy) of IORT (11 MeV electrons) delivered to retroperitoneal tissues including the great vessels and ureters, to a loop of defunctionalized small bowel, or to the extrahepatic bile duct. One control animal received an aortic transection and reanastomosis at the time of laparotomy; another control received laparotomy alone. This paper describes the late effects of single-fraction IORT occurring 3-5 years following treatment. RESULTS AND CONCLUSION: Dogs receiving IORT to the retroperitoneum through a 4 x 15 cm portal showed few gross or histologic abnormalities at 20 Gy. At doses ranging from 30-45 Gy, radiation changes in normal tissues were consistently observed. Retroperitoneal fibrosis with encasement of the ureters and great vessels developed at doses > or = 30 Gy. Radiation changes were present in the aorta and vena cava at doses > or = 40 Gy. A 30 Gy dog developed an in-field malignant osteosarcoma at 3 years which invaded the vertebral column and compressed the spinal cord. A 40 Gy animal developed obstruction of the right ureter with fatal septic hydronephrosis at 4 years. Animals receiving IORT through a 5 cm IORT portal to an upper abdominal field which included a defunctionalized loop of small bowel, showed a few gross or histologic abnormalities at a dose of 20 Gy. At 30 Gy, hyaline degeneration of the intestinal muscularis layer of the bowel occurred. At a dose of 45 Gy, internal intestinal fistulae developed. One 30 Gy animal developed right ureteral obstruction and hydronephrosis at 5 years. A dog receiving 30 Gy IORT through a 5 cm portal to the extrahepatic bile duct showed diffuse fibrosis through the gastroduodenal ligament. These canine studies contribute to the area of late tissue tolerance to IORT.

Anastomosis, Surgical↗

PubMed1993

Intraoperative radiotherapy in retroperitoneal sarcomas. Final results of a prospective, randomized, clinical trial.

Thirty-five patients with surgically resected sarcomas of the retroperitoneum were enrolled in a prospective, randomized, clinical trial comparing 20-Gy intraoperative radiotherapy in combination with postoperative low-dose (35- to 40-Gy) external-beam radiotherapy with postoperative high-dose (50- to 55-Gy) external-beam radiotherapy alone. Chemotherapy with doxorubicin hydrochloride, cyclophosphamide (anhydrous), and methotrexate sodium was used for a portion of the trial. Fifteen patients who received intraoperative radiotherapy and 20 control patients were followed up for a minimum of 5 years (median follow-up, 8 years). Median survival times were similar for the group that received intraoperative radiotherapy (45 months) and the control group (52 months). There were no indications of benefit from adjunctive chemotherapy. The number of locoregional recurrences was significantly lower among those who received intraoperative radiotherapy (six of 15) than control patients (16 of 20). Patients who received intraoperative radiotherapy had fewer complications of disabling radiation-related enteritis (two of 15) than control patients (10 of 20), but radiation-related peripheral neuropathy was more frequent among those who received intraoperative radiotherapy (nine of 15) than among control patients (one of 20).

Adult↗

PubMed1993

Randomized trial of intraoperative radiotherapy in carcinoma of the stomach.

A prospectively randomized controlled clinical trial was performed comparing surgical resection and intraoperative radiotherapy (IORT) with conventional therapy in adenocarcinoma of the stomach. Patients in the experimental group underwent gastrectomy, and IORT was administered to their gastric bed (20 Gy using 11 to 15 MeV electrons). Patients in the control group underwent gastrectomy alone for early-stage lesions confined to the stomach (stages I to II) or resection and postoperative external beam radiotherapy to the upper abdomen (50 Gy using 6 to 10 mV photons) for advanced-stage lesions extending beyond the gastric wall (stages III to IV). One hundred patients were screened for the study, of whom 60 were randomized and underwent exploratory surgery. Nineteen patients were excluded intraoperatively because of unresectability or metastatic disease, leaving 41 patients in the study. Seven patients (17%) died of complications. The median survival for patients with tumors of all stages was 25 months for the IORT group and 21 months for the control group (p = 0.99). Locoregional disease failures occurred in 7 of 16 (44%) IORT patients and in 23 of 25 (92%) control patients (p < 0.001). Complication rates were similar between IORT and control patients. Although IORT failed to afford a significant advantage over conventional therapy in overall survival, IORT did significantly improve control of locoregional disease.

Actuarial Analysis↗

PubMed1992

An electronic medical record system with direct data-entry and research capabilities.

The transfer of medical records from a paper system to a computer-based system is inevitable. However, the widespread acceptance of electronic medical records has been delayed by problems such as high cost, inefficiency, data entry errors and poor physician acceptance. We have developed a database system that has overcome these difficulties and now serves as an electronic medical record. Our system has been in use for a year and a half, and currently contains information on over two thousand patients. The database provides an electronic radiation oncology chart containing patients' demographic information, technical treatment data and dictated reports. All dictated notes are captured, including consultation notes, treatment summaries, on-treatment visits, letters and follow up reports. The system provides data validation upon entry, required few additional software or hardware purchases, and allows for efficient retrieval of data. Unlike other database systems which require the hiring of data entry clerks to input the data, ours combines transcription and data entry. The database runs on a local area network of computers and uses a commercially available relational database package. It makes extensive use of mouse interface features such as pull-down menus, pop-up lists, buttons, multi-page forms, and scrolling fields, making the system easy to use with minimal training. Many custom features are built in, such as help screens, control functions, audit trails, and a system that keeps track of each patient's referring and other relevant physicians. For research purposes, the system has the capability to perform survival analyses on arbitrary user-defined subsets of patients. Data may also be exported transparently to statistical packages for other types of analyses.

Data Display↗

PubMed1992

Adjuvant postoperative radiation therapy for rectal adenocarcinoma.

From October 1975 to August 1988, 261 patients at high risk for local recurrence after curative resection of rectal carcinoma underwent high-dose postoperative irradiation. Patients received 45 Gy by a 4-field box usually followed by a boost to 50.4 Gy or higher when small bowel could be excluded from the reduced field. Since January 1986, patients also received 5-fluorouracil (5-FU) for 3 consecutive days during the first and last week of radiotherapy. Five-year actuarial local control and disease-free survival decreased with increasing stage of disease; patients with Stage B2 and B3 disease had local control rates of 83% and 87% and disease-free survivals of 55% and 74%, respectively. In patients with Stage C1 through C3 tumors, local control rates ranged from 76% to 23%, and disease-free survivals ranged from 62% to 10%, respectively. For patients with Stage C disease, disease-free survival decreased progressively with increasing lymph node involvement, but local control was independent of the extent of lymph node involvement. For each stage of disease, local control and disease-free survival did not correlate with the dose of pelvic irradiation. Preliminary data from this study suggest a trend toward improved local control for patients with Stage B2, C1, and C2 tumors who receive 5-FU for 3 consecutive days during the first and last weeks of irradiation compared with patients who do not receive 5-FU. Current prospective randomized studies are addressing questions regarding the optimum administration of chemotherapy with pelvic irradiation for patients following resection of rectal carcinoma.

Adenocarcinoma↗

PubMed1992

Adjuvant therapy of rectal cancer.

The treatment of rectal cancer has gradually evolved based on our knowledge of the failure patterns. Although results with surgery alone are good in patients with disease limited to the bowel wall and with no lymph node spread, surgery alone is less effective for more advanced disease. Treatment strategies that combine pelvic radiation therapy and 5-fluorouracil-based chemotherapy regimens have significantly improved local recurrence rates and overall survival results for patients with disease extending through the bowel wall or those with positive lymph nodes. Recent studies suggest that methyl CCNU can be dropped from chemotherapy regimens without loss of efficacy. Newer strategies being investigated include modulations of 5-fluorouracil with agents such as leucovorin and levamisole, possibly in combination, and continuous infusions of 5-fluorouracil.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

Combined radiotherapy and chemotherapy in the treatment of gastrointestinal malignancies.

There has long been an interest in the use of combination chemotherapy/radiotherapy in the treatment of gastrointestinal tumors. Almost all such regimens combined 5-fluorouracil (5-FU) with radiotherapy. Work has been done in gastric cancer, pancreatic cancer, and colon and rectal cancer, all of which demonstrate an advantage in certain clinical situations for combined-modality therapy. In locally advanced pancreatic cancer, radiotherapy/5-FU has been shown to improve survival compared with radiotherapy alone, while in resectable carcinoma of the pancreas, the combination has been demonstrated to improve long-term survival compared with surgery alone. In patients with gastric cancer the data are more limited, but indications are that combined-modality therapy may benefit certain subsets of patients. Little information exists in colon cancer, but patterns of failure suggest a potential role for adjuvant radiotherapy/5-FU. Studies are being designed to test the hypothesis. In rectal cancer, a significant amount of data exists to support the value of radiotherapy/5-FU-based chemotherapy as an adjuvant in patients with stages B2 and C tumors. At present, studies are being run or analyzed to define whether modulation of 5-FU with leucovorin or levamisole, or whether the use of continuous infusion 5-FU, will improve the therapeutic efficacy of the adjuvant therapy.

Combined Modality Therapy↗

PubMed1991

Intraoperative electron beam radiation therapy for retroperitoneal soft tissue sarcoma.

From December 1981 to December 1989, 20 patients with primary or recurrent retroperitoneal sarcoma received 4000 to 5000 cGy of external beam radiation therapy (EBRT) in conjunction with surgical resection and intraoperative radiation therapy (IORT). Seventeen of 20 patients underwent complete (14 patients) or partial (3 patients) resection. Three patients had shown evidence of metastases after EBRT by the time of surgery. The 4-year actuarial local control and disease-free survival rates of the 17 patients undergoing resection were 81% and 64%, respectively. Twelve patients received IORT at the time of resection for microscopic disease (10 patients) or gross residual sarcoma (2 patients). Of the ten patients receiving IORT for microscopic tumor, one patient has died of local failure and peritoneal sarcomatosis and two patients have died of distant metastases only. The remaining seven patients are disease-free. One patient treated for gross residual sarcoma has experienced a local failure 1 year after IORT and is without disease 7 years after salvage chemotherapy. The other patient treated for gross residual sarcoma has died of local failure. Five patients did not receive IORT at the time of resection because of the extensive size of the tumor bed. Three of these patients are disease-free with one patient alive with lung metastases and one patient dying of hepatic metastases. Aggressive radiation and surgical procedures appear to provide satisfactory resectability and local control with acceptable tolerance.

Adolescent↗

PubMed1991

Intraoperative electron beam radiation therapy for recurrent locally advanced rectal or rectosigmoid carcinoma.

A multimodality approach of moderate-dose to high-dose preoperative radiation therapy, surgical resection, and intraoperative electron beam radiation therapy (IORT) has been used for patients with locally recurrent rectal or rectosigmoid carcinoma. The 5-year actuarial local control and disease-free survival for 30 patients undergoing this treatment program were 26% and 19%, respectively. The most important factor predicting a favorable outcome was complete resection with negative pathologic resection margins. The determinant local control and disease-free survival for 13 patients undergoing complete resection were 62% and 54%, respectively, whereas for 17 patients undergoing partial resection these figures were 18% and 6%, respectively. There did not appear to be a difference in local control or survival based on the original surgical resection (abdominoperineal resection versus low anterior resection). However, the likelihood of obtaining a complete resection after preoperative radiation therapy was higher in patients who had previously undergone a low anterior resection than patients undergoing prior abdominoperineal resection. For the 30 patients undergoing external beam irradiation, resection, and IORT, the most significant toxicities were soft tissue or sacral injury and pelvic neuropathy. Efforts to further improve local control are directed toward the concurrent use of chemotherapy (5-fluorouracil with and without leucovorin) as radiation dose modifiers during external beam irradiation and the use of additional postoperative radiation therapy.

Adult↗