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Biomedical subjects

J E Tepper

Publications and source records attributed to J E Tepper.

At least 73 records · Page 4Linked to original sources
PubMed1987

The role of misonidazole combined with intraoperative radiation therapy in the treatment of pancreatic carcinoma.

We tested the efficacy of the hypoxic cell sensitizer misonidazole in conjunction with intraoperative electron beam radiation therapy (IORT) and external beam irradiation in patients with locally advanced, nonmetastatic adenocarcinoma of the pancreas. Misonidazole was delivered intravenously (IV) at a dose of 3.5 g/m2 in conjunction with IORT of 1,500 to 2,000 cGy to the pancreas. Additional external beam radiation as administered to 4,960 cGy. The study was based on the premise that the effect of misonidazole would be maximized when a high dose of the drug was administered and, thus, high hypoxic cell sensitization could be obtained when using a high single dose of radiation where the hypoxic fraction would be expected to dominate in the survivors. In a nonrandomized study of 41 patients treated with misonidazole and 22 without, the 1-year local control was 67% and 55%, and 1-year survival was 50% and 77%, respectively. Although there was a bias towards larger tumors in the patients treated with the sensitizer, we were unable to demonstrate an advantage to misonidazole in this clinical situation.

Actuarial Analysis↗
PubMed1987

[Peroperative irradiation: the Massachusetts General Hospital technic and current experience].

Intra-operative radiotherapy (IORT) is a technique developed since the early 60s mainly in Japan and in the U.S.A. It usually consists of a single fraction of electrons given intra-operatively. Doses range from 10 to 35 Gy and may be combined with external beam irradiation. The salient advantages are: 1) a better target volume definition with the surgeon; 2) the possibility of removing normal structures (such as the small bowel) from the beam and of so delivering a much higher tumor dose. The disadvantages are: 1) theoretically, a lesser effect on hypoxic cells compared with a fractionated regimen; 2) a requirement for perfect cooperation between surgeon and radiotherapist; 3) a cumbersome apparatus. From pilot studies conducted so far, it appears that advanced poorly or unresectable rectal carcinomas, retroperitoneal soft tissue sarcomas and gastric carcinomas may benefit from such an approach while resected or unresectable pancreatic carcinomas, in spite of extensive evaluation, do not. The management of prostatic, bladder, cerebral, intrathoracic and gynecologic malignancies with IORT is undergoing active prospective studies in some 60 Japanese, American (and, in 1986, 7 French) centers. The major technical issues and drawbacks of this technique will also be discussed.

Boston↗
PubMed1986

Adjuvant postoperative radiation therapy in the management of adenocarcinoma of the colon.

Between April 1976 and January 1981, 80 patients with completely resected adenocarcinoma of the colon who were at high risk for local tumor recurrence received adjuvant postoperative irradiation to the tumor bed. Doses of 4300 to 6300 cGy were delivered to the tumor bed, with no chronic toxicity in 70 of 80 patients. Only two patients required operative intervention for treatment complications. Treatment protocol, selection criteria, and details of irradiation are discussed. Actuarial local failure rates at 3 years were 6%, 5%, 17%, 43% for Stages B2, B3, C2, and C3, respectively, and actuarial survival rates at 3 years were 84%, 84%, 73%, and 49%, respectively. The survival figures for Stages B3, C2, and C3 appear superior to published historic controls as well as to data from the study institution, and suggest an advantage to the use of adjuvant radiation therapy in patients with moderately advanced colonic carcinomas.

Actuarial Analysis↗
PubMed1986

Intraoperative electron beam radiotherapy in the treatment of unresectable rectal cancer.

We treated 29 patients who had primarily unresectable rectal cancer with an aggressive combined surgical and radiotherapeutic approach. Each patient received 5,040 rad of preoperative external beam radiation therapy. Eighteen patients responded adequately to allow resection of all macroscopic tumor; 11 patients underwent resection but had residual cancer in the pelvis. A single bolus of 1,000 to 2,000 rad of intraoperative electron beam radiation was given. Follow-up time ranged from three to 66 months, with a median of 43 months for living patients. The actuarial local control rate at 36 months for the entire group was 87%. In the group of 18 patients who underwent resection, the local control rate was 92%, with a three-year survival rate of 70%. Our results are considerably improved over our prior experience without intraoperative radiation therapy--a 57% local control rate and a 30% three-year survival rate.

Actuarial Analysis↗
PubMed1986

Laparoscopy in the staging and planning of therapy for pancreatic cancer.

Although staging of pancreatic cancer is critical to the planning of therapy, many patients come to laparotomy with liver or peritoneal metastases not suspected or detected during conventional preoperative testing. We performed laparoscopic examinations as part of the staging evaluation of 40 patients with proved pancreatic cancer who were candidates for curative resection or intraoperative radiotherapy. In each patient, laparoscopy was the last test before laparotomy and was carried out only if all other test results were negative for metastases. In 14 of 40 patients, single, small (1 to 2 mm) metastatic nodules were detected and verified by biopsy in the liver (6 patients), on the parietal peritoneum (7 patients), and in the omentum (1 patient). It is likely that several of these lesions would have been overlooked at routine exploration. Because of the positive findings, therapy was altered in all 14 patients. None received intraoperative radiotherapy, nine who did not have jaundice were discharged without operation, three had biliary or gastric bypass only, and two were treated by percutaneous biliary stenting. Of the 26 patients who had negative findings on laparoscopic examination, the absence of gross metastasis was confirmed at laparotomy in 23. Three false-negative findings were caused by incomplete examination of the liver in two patients and a central liver lesion in one patient. Therefore, 43 percent of all patients (17 of 40) had demonstrable but unsuspected nonlocal metastases, and laparoscopic examination detected 82 percent (14 of 17) of these. The overall accuracy of laparoscopy was 93 percent and that of examination with negative findings, 88 percent. In eliminating useless laparotomy and redirecting treatment plans, laparoscopy contributes significantly both to the proper management of patients with pancreatic cancer and to increased efficiency of resource utilization.

Adenocarcinoma↗
PubMed1986

Adjuvant irradiation of gastrointestinal malignancies: impact on local control and tumor cure.

Radiation therapy has recently been used more frequently in the adjuvant treatment of gastrointestinal malignancies. A number of studies have shown a high local failure in patients with Stages B2 and C rectal carcinomas and in Stages B3, C2 and C3 colon carcinomas. In rectal cancer, both randomized and non-randomized studies have demonstrated improved local control and survival with the use of adjuvant radiation. Randomized studies have not been performed in colon cancer, but preliminary data from MGH indicate improved local control and survival in some patient subsets with the use of local irradiation after resection. Both gastric and pancreatic cancer have a greater propensity to distant metastases. A review of failure patterns after resection has, nonetheless, shown a high incidence of local recurrence and small prospective randomized studies have recently demonstrated a survival advantage with the use of adjuvant irradiation.

Clinical Trials as Topic↗
PubMed1986

Impact of improved local control on survival in patients with soft tissue sarcoma.

An estimate has been made of the gain in survival if the local failure rate for sarcoma of soft tissue was reduced to zero by the application of new treatment methods. The assumption is that the loss, due to distant metastasis and intercurrent disease among patients who achieve local control by the current treatment, would be the same among new local controls. For patients with stage M0 disease at diagnosis (all sites, all histological types), the current local failure rate is approximately 30%. By eliminating these failures, the overall survival rate would be expected to increase by 10-20 percentage points.

Combined Modality Therapy↗
PubMed1986

Renal complications secondary to radiation treatment of upper abdominal malignancies.

A retrospective review of all patients undergoing radiotherapy for carcinoma of the colon, pancreas, stomach, small bowel and bile ducts, lymphomas of the stomach, and other GI sites and retroperitoneal sarcomas was completed to assess the effects of secondary irradiation on the kidney. Eighty-six adult patients were identified who were treated with curative intent, received greater than 50% unilateral kidney irradiation to doses of at least 2600 cGy and survived for 1 year or more. Following treatment, the clinical course, blood pressure, addition of anti-hypertensive medications, serum creatinine and creatinine clearance were determined. Creatinine clearance was calculated by the formula: creatinine clearance equals [(140-age) X (weight in kilograms)] divided by (72 X serum creatinine) which has a close correlation to creatinine clearances measured by 24 hr. urine measurements. The percent change in creatinine clearance from pre-treatment values was analyzed. Of the thirteen patients with pre-radiotherapy hypertension, four required an increase in the number of medications for control and nine required no change in medication. Two patients developed hypertension in follow-up, one controlled with medication and the other malignant hypertension. Acute or chronic renal failure was not observed in any patient. The serum creatinine for all 86 patients prior to radiation therapy was below 2 mg/100 ml; in follow-up it rose to between 2.2-2.9 mg/100 ml. in five patients. The mean creatinine clearance for all 86 patients prior to radiotherapy was 77 ml/minute and for 16 patients with at least 5 years of follow-up it was 62 ml/minute. The mean percent decrease in creatinine clearance appeared to correspond to the percentage of kidney irradiated: for 38 patients with only 50% of the kidney irradiated the mean percent decrease was 10%, whereas for 31 patients having 90 to 100% of the kidney treated the decrease was 24%. Although physiologic changes were seen in patients receiving 50% or more unilateral kidney irradiation, the development of significant clinical sequelae was limited to one patient.

Abdominal Neoplasms↗
PubMed1986

Quality control parameters of intraoperative radiation therapy.

We have tried to outline many of the factors which must be considered in the technical delivery of IORT and in subsequent evaluation of these patients. Unless careful attention is given to details of patient selection, surgery, pathology, radiation therapy and follow-up, it is likely that a vast morass of data will be obtained which will be very difficult to interpret. It is the hope of the IORT Working Group that other institutions using IORT will employ our recommendations with regard to dosimetry, follow-up, and the general technical approach. This will likely lead to an earlier understanding of the exact role of this modality in cancer therapy today.

Combined Modality Therapy↗
PubMed1986

Staging rectal cancer by MR and CT.

Sixteen patients with known rectal cancer were evaluated and staged with CT and MR, and at surgery. Detailed evaluation of the pathologic specimens was performed and correlated with CT and MR to determine the accuracy of staging. Most of the cases were advanced stages, and both CT and MR were equally effective in staging. Prone positioning using an air-distension technique was equally important for CT and MR examinations. Because of a positive contrast material (iodine), adequate CT examinations could be performed without prior bowel preparation; however, bowel cleansing was necessary for MR examinations. Both techniques could identify the primary tumor and invasion into perirectal fat and local organs. Neither CT nor MR were able to assess the extent of bowel-wall infiltration or tumor spread to normal size perirectal lymph nodes.

Air↗
PubMed1985

Radiation therapy alone for sarcoma of soft tissue.

Fifty-one patients have been treated with radiation therapy alone for soft tissue sarcomas, with 72.5% eligible for more than 5-year follow-up. Thirty-six of 51 patients received a radiation dose of 6400 cGy (or its equivalent) or greater. Careful attention was paid to the radiation therapy technique, using multiple angled fields, tissue-compensating wedges, immobilization devices, etc., in order to preserve a good functional result. Eleven of 51 patients are alive with no evidence of disease. The overall 5-year survival and local control rates were 25.1% and 33% respectively. For patients treated to a dose of 6400 cGy or greater, the 5-year survival and local control were 28.4% and 43.5%, respectively. Local control was better for tumors less than 5 cm diameter (87.5%) than in tumors 5 to 10 cm diameter (53%) or greater than 10 cm (30%). Only four patients in this series had a grade I tumor, and no survival difference could be detected between Grade 2 and Grade 3 tumors. This series indicates that radiation therapy alone can control tumor in a portion of patients with soft tissue sarcomas.

Adolescent↗
PubMed1985

Radiation therapy of soft tissue sarcomas.

Radiation therapy combined with conservative surgical resection has been shown to be an effective method of producing local control in patients with soft tissue sarcomas. In 170 patients treated with this combination at the Massachusetts General Hospital (MGH) the 5-year actuarial local control rate was 84% and the 5-year survival rate 69%. For tumors in the extremity, treatment resulted in limbs with normal or near-normal function. The combination of preoperative irradiation to doses of approximately 5000 cGy, followed by local resection and an additional dose of 1400 cGy, delivered either intraoperatively or postoperatively, has theoretical advantages in terms of decreasing tumor implantation, facilitating a conservative surgical resection, and assuring full cooperation between the various physicians. Sixty patients have been treated with this approach at the MGH with good local control and without major problems with wound healing. When surgical resection is not performed, radiation therapy alone can produce local control and survival in 44% and 28% of patients, respectively.

Combined Modality Therapy↗
PubMed1985

Treatment planning for colorectal cancer: radiation and surgical techniques and value of small-bowel films.

For colorectal cancer, the adjuvant radiation dose levels required to achieve a high incidence of local control closely parallel the radiation tolerance of small bowel (4500-5000 rad), and for patients with partially resected or unresected disease, the dose levels exceed tolerance (6000-7000 rad). Therefore, both the surgeon and the radiation oncologist should use techniques that localize tumor volumes and decrease the amount of small intestine within the irradiation field. Surgical options include pelvic reconstruction (reperitonealization, omental flaps, retroversion of uterus, etc.) and clip placement. Radiation options include the use of radiographs to define small bowel location and mobility combined with treatment techniques using multiple fields, bladder distention, shrinking or boost fields, and/or patient position changes (prone, decubitus, etc.). When both specialties interact in optimum fashion, local control can be increased with minimal risks to achieve a suitable therapeutic ratio.

Colonic Neoplasms↗
PubMed1985

Obstructive and perforative colonic carcinoma: patterns of failure.

Carcinoma of the colon complicated by obstruction or perforation has been recognized as having a poorer prognosis than tumors without obstruction or perforation. To clarify the natural history, failure patterns, and implications for adjuvant treatment after resection with curative intent, a review of the recent Massachusetts General Hospital (MGH) experience was undertaken. From 1970 to 1977, 77 patients with obstructive colonic carcinoma and 34 patients with localized perforation at the tumor site were identified and compared with a control group of 400 patients without obstruction or perforation undergoing curative resection. All patients were observed for a minimum of five years or until the patient's death. The actuarial five-year survival and disease-free survival rates in patients with obstruction was 31% and 44%, respectively, in contrast to 59% and 75% in control patients. For patients with localized perforation, the five-year actuarial survival and disease-free survival rates were 44% and 35%, respectively. Of the 77 patients with obstructing tumors, 32 patients (42%) developed local failure--nine with local failure only and 23 patients with local failure and distant metastases. Thirty-four patients (44%) developed distant metastases. Fifteen (44%) patients of 34 with perforative colonic carcinoma had local failure. Distant metastases occurred in 15 patients (44%). The incidence of local failure and distant metastases in the control group was 14% and 21%, respectively. The rate of local failure and distant metastases increased with stage and was generally higher stage for stage than in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1985

The role of radiation therapy in the treatment of sarcoma of soft tissue.

The data presented indicate that the combination of function-preserving surgery and radiation therapy is of value in the treatment of soft tissue sarcomas of the extremity. Local control is obtained in approximately 85% of patients and with survival results comparable to those obtained in patients treated with radical surgery. The one randomized series of patients treated with conservative resection and radiation compared to amputation has shown no difference in overall survival. These local control results have been obtained while maintaining good functional results. Combined local resection and radiation is an appropriate treatment option in a large proportion of patients with soft tissue sarcomas.

Fibrosarcoma↗
PubMed1984

Relative biological effectiveness of modulated proton beams in various murine tissues.

The relative biological effectiveness (RBE) of proton beams produced by Harvard University 160 MeV synchrocyclotron was studied in various murine tissues. Reference radiation was Cobalt-60 gamma-rays from a teletherapy unit at the Massachusetts General Hospital. Animals were C3Hf/Sed mice derived from our defined flora mouse colony. Test tissues are: lens, lung, testes and tail vertebrae. The RBE of the third generation isotransplants of a spontaneous mouse mammary carcinoma was also investigated. The proton and Cobalt-60 irradiations were carried out simultaneously by 2 teams. The dose response curves obtained for testes weight loss and growth stunting of tail vertebrae indicated that the RBE for our protons was independent of radiation dose in the range of 0.4 to 16 Gy. This finding was identical to our previous studies of the murine fibrosarcoma, skin and small intestine. The RBE values for lens and lung tissues were obtained by determining radiation dose to result in a complete cataract in half the irradiated eyes in 210 days and a 50% mortality in 180 days respectively. We have studied proton RBE in 7 normal tissues and 2 tumors including previously reported results. The RBE values for these tissues were found to fall between 1.09 and 1.32. No significant differences in the proton RBE were found between the several normal and tumor tissues studied.

Animals↗