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Biomedical subjects

R R Dobelbower

Publications and source records attributed to R R Dobelbower.

At least 19 recordsLinked to original sources

Intraoperative electron beam radiation therapy: technique, dosimetry, and dose specification: report of task force 48 of the Radiation Therapy Committee, American Association of Physicists in Medicine.

Intraoperative radiation therapy (IORT) is a treatment modality whereby a large single dose of radiation is delivered to a surgically open, exposed cancer site. Typically, a beam of megavoltage electrons is directed at an exposed tumor or tumor bed through a specially designed applicator system. In the last few years, IORT facilities have proliferated around the world. The IORT technique and the applicator systems used at these facilities vary greatly in sophistication and design philosophy. The IORT beam characteristics vary for different designs of applicator systems. It is necessary to document the existing techniques of IORT, to detail the dosimetry data required for accurate delivery of the prescribed dose, and to have a uniform method of dose specification for cooperative clinical trials. The specific charge to the task group includes the following: (a) identify the multidisciplinary IORT team, (b) outline special considerations that must be addressed by an IORT program, (c) review currently available IORT techniques, (d) describe dosimetric measurements necessary for accurate delivery of prescribed dose, (e) describe dosimetric measurements necessary in documenting doses to the surrounding normal tissues, (f) recommend quality assurance procedures for IORT, (g) review methods of treatment documentation and verification, and (h) recommend methods of dose specification and recording for cooperative clinical trials.

Combined Modality Therapy

Intraluminal brachytherapy in the treatment of pancreas and bile duct carcinoma.

PURPOSE: A new method of palliation of malignant obstructive jaundice is presented. METHODS AND MATERIALS: Twelve patients with carcinoma of the extrahepatic bile ducts (EHBD-five patients) or pancreatic head (PH-seven patients) received radiation therapy between 1988 and 1991. Percutaneous transhepatic biliary drainage was performed in four EHBD patients and an endoprosthesis was placed during endoscopic retrograde cholangiopancreatography (ERCP) in the other eight patients. All 12 received intraluminal brachytherapy (ILBT): 20-50 Gy calculated at 1 cm from the Iridium-192 (192Ir) wire. In four PH patients the source was placed in the duct of Wirsung; in the other eight patients ILBT was performed via the common bile duct. Five of the seven PH patients and one of the five EHBD patients received External Beam Radiation Therapy (EBRT): 26-50 Gy, alone or with concomitant 5-Fluorouracil (5-FU). RESULTS: Cholangitis occurred in six patients. Three PH patients treated with EBRT+ILBT developed gastrointestinal toxicities. With a minimum follow-up of 18 months, median survival times were 14 months (EHBD) and 11.5 months (PH); one of the seven PH patients is alive (29 months) and two of the EHBD patients are alive (18 and 43 months). All patients had satisfactory control of jaundice. CONCLUSIONS: The results in the EHBD patients suggest that the addition of ILBT after biliary drainage prolongs survival. Further experience is necessary to determine whether ILBT in the common bile duct and/or in the duct of Wirsung may be, in PH patients, an alternative boost technique to Interstitial Brachy-therapy (IBT) or Intraoperative Electron Beam Radiation Therapy (IOEBRT).

Aged

Use of ileal urinary diversion in conjunction with intraoperative radiotherapy.

Intraoperative radiotherapy (IORT) was introduced in the 1970s as a new modality of cancer therapy. It has been especially useful after local irradiation or surgical failure. We report on the use of IORT in 13 patients with pelvic tumors requiring urinary diversion. All 13 were managed with ileal conduits. Despite the associated problems of prior abdominal procedures (11/13 patients), prior external beam radiation to the pelvis (11/13 patients), systemic chemotherapy (4/13 patients), and prolonged operative time (> 10 hours), perioperative mortality (1/13) and morbidity rates were low. We conclude that in cases of prior colonic resection and pelvic radiation, potentially irradiated ileum can be safely used for urinary diversion.

Aged

3-D reconstruction of Ir-192 implant dosimetry for irradiating gingival carcinoma on the mandibular alveolar ridge.

A recurrent cancer in the gingiva has been treated by specially fabricating a dental acrylic appliance. This replica of the floor of the mouth, gums, and teeth was constructed with the use of a vinyl polysiloxine impression material. The tumor boundaries were marked in the fabricated appliance with four metal wires to localize the surface and periphery of the tumor. The appliance was molded to hold Ir-192 wires in near contact with the target surface and to allow afterloading. A specially designed lead shield was imbedded onto the dorsal surface of the appliance so as to reduce dose to the tongue and maxillary structures of the mouth. Simulation films and 3-D treatment planning were used to generate isodose distributions and to allow preplanning. The dose calculation algorithm was modified to account for the attenuation in the lead shield represented in three dimensions. The Ir-192 mold was successfully applied for 38 hours in two sessions 1 week apart.

Aged

Radiation therapy and 5-fluorouracil modulated by leucovorin for adenocarcinoma of the pancreas. A phase I study.

This Phase I study was designed to build on the Gastrointestinal Tumor Study Group's experience with combined modality therapy in patients with pancreatic cancer. Thirteen patients with adenocarcinoma of the pancreas received weekly 5-fluorouracil by rapid intravenous infusion midway through a 2-h infusion of high dose leucovorin during external beam radiation therapy. Twelve patients received 100% of planned external beam radiation; treatment delays occurred in only three. Four patients received 100% of planned chemotherapy doses. Leukopenia and thrombocytopenia caused reduction of the number of chemotherapy doses given during radiation in six patients; diarrhea, severe nausea and vomiting, and wound abscess caused reduction in three patients. Ten patients were evaluable for response; two had complete responses, one had a partial response, and two had minor responses. In this small series baseline and post-treatment CA 19-9 levels predicted and correlated with response. We conclude that radiation and 5-FU modulated by leucovorin is a tolerable treatment regimen for carcinoma of the pancreas, with preliminary suggestion of activity, that warrants further Phase II testing.

Adenocarcinoma

Carcinoma of the pancreas: a personal experience with 100 cases.

One hundred patients with pancreatic cancer were evaluated between March 1981 and December 1989. This study showed that 61 were not candidates for definitive surgery because of nonoperability (28 patients) or nonresectability (33 patients). An additional 25 patients had cancers that were unresectable because of metastases (13 patients) or local spread of disease (12 patients) discovered at laparotomy. Fourteen patients had resectable cancers. Ten were treated by total pancreatectomy, three by distal pancreatectomy and one by pancreatoduodenectomy (Whipple). There were two operative mortalities. The median patient survival time was 20.5 months. Two patients survived 5 years. Five patients are alive at 3, 14, 18, and 47 months. Palliative surgical procedures performed in 18 patients included 10 biliary bypasses, 9 gastrojejunostomies, and 6 T-tube placements. This was associated with an operative mortality rate of 11%. The median survival time was 5 months. Other palliative measures included endoscopic placement of biliary and pancreatic stents (47 patients, 2.7% mortality rate), endoluminal radiation therapy, interstitial radiation therapy and external beam radiation therapy. The median survival time of patients so treated was 4.5 months.

Adult

Intraoperative electron beam radiation therapy (IOEBRT) for carcinoma of the exocrine pancreas.

The abdominal cavities of 50 patients were explored in a specially constructed intraoperative radiotherapy operating amphitheater at the Medical College of Ohio. Twenty-six patients were treated with intraoperative and postoperative precision high dose external beam therapy, 12 with intraoperative irradiation but no external beam therapy, and 12 with palliative surgery alone. All but two patients completed the postoperative external beam radiation therapy as initially prescribed. The median survival time for patients treated with palliative surgery alone was 4 months, and that for patients treated with intraoperative radiotherapy without external beam therapy was 3.5 months. Patients undergoing intraoperative irradiation and external beam radiation therapy had a median survival time of 10.5 months. Four patients died within 30 days of surgery and two patients died of gastrointestinal hemorrhage 5 months posttreatment.

Adenocarcinoma

Intraoperative radiation therapy of pancreatic carcinoma: a report of RTOG-8505. Radiation Therapy Oncology Group.

The Radiation Therapy Oncology Group in 1985 began a study of IORT plus external beam radiation therapy for patients with locally unresected, non-metastatic pancreatic cancer. Patients were treated with a combination of 2000 cGy of IORT and postoperative external beam radiation therapy to 5040 cGy in combination with IV 5-FU (500 mg/m2/day on the first 3 days of the external beam treatment). As patients were registered on study prior to exploration, it was expected that a number of patients would be excluded from further analysis at the time of surgery. Eighty-six patients were entered on study through 6/1/88 and analyzed through 4/90. Fifty-one patients were fully analyzable. Median survival time of the 51 patients was 9 months with an 18-month actuarial survival rate of 9%. Local control could not be adequately evaluated in this multi-institutional study. Major postoperative complications were not excessive and occurred in 12% of patients. Two patients had major late morbidity leading to death, one from duodenal bleeding and the second from biliary obstruction. Although this study does demonstrate the feasibility of IORT in a multi-institutional setting, it does not demonstrate any advantage of IORT over conventional therapy for this disease.

Carcinoma, Intraductal, Noninfiltrating

Flow cytometric DNA content analysis of paraffin block embedded endometrial carcinomas.

Flow cytometry is being used as an aid in planning the treatment of patients with various malignancies. We report our experience with DNA content analysis on paraffin-embedded carcinomas. Hospital, radiation therapy, clinic, and pathology records were reviewed in 139 cases of endometrial carcinoma diagnosed between December 1980 and December 1986. Patients having Stage IV tumors, endometrial sarcomas, dual primary tumors, or incomplete records were eliminated from the analysis, which left 98 evaluable patients. This report outlines our experience with the first 20 patients. Five of 20 (25%) specimens demonstrated DNA content consistent with aneuploidy, median coefficient of variance of 5.3%. The median survival time of these five patients is 55 months, with three dying of cancer and one patient dying of other causes but with metastatic disease. The median %S phase was 3.7% in the 15 patients comprising the DNA content diploid population, median coefficient of variance 5.4%. No patient whose tumor showed S-phase cells below 3.7% died of endometrial cancer. Four of 7 patients developed recurrent cancer with 3 of the 4 patients dying of disease in the high %S phase group. The median patients survival time in the DNA content diploid population was 73 (range: 17-98) months. Patients with 3.7% or below S-phase cells had a median survival time of 75 (range: 40-98) months whereas the median survival time was 48 (range: 17-89) months for patients having a %S phase fraction above 3.7%. Although the number of patients studied is small, it appears that DNA content aneuploid tumors are frequently "upstaged" at surgery. These patients may not benefit from preoperative irradiation. Accurate determination of the %S phase fraction in DNA content diploid tumors may possibly identify patients with a poorer prognosis who may benefit from adjuvant therapy.

Aneuploidy

Association of malignant lymphoma with pancreatic adenocarcinoma: a clinicopathologic study of three patients.

Three patients with pancreatic adenocarcinoma are studied who had a prior history of malignant lymphoma. No common predisposing factors for the development of pancreatic adenocarcinoma were identified. We conclude that patients with malignant lymphoma who have new or persistent pancreatic masses must be evaluated for the possibility of a second primary neoplasm.

Adenocarcinoma

Intraoperative radiation therapy for pancreatic, biliary and gastric carcinoma: the US experience.

The experience with pancreatic, biliary and gastric cancer in the US has demonstrated that IORT is technically a feasible and therapeutically relatively safe modality. However, much research remains to be done. The toxicity in humans of single large dose radiation to normal tissue has not been firmly established. Clinical studies must be able to demonstrate the efficacy of IORT as well as a therapeutic advantage for this approach. IORT is potentially a very effective adjuvant therapy in treating tumors which are technically difficult to treat surgically or which have a high rate of recurrence following radical surgery. The combination of surgery and IORT may improve local control of the tumor by removing gross disease and identifying areas of potential risk for recurrence. Regional and distant failure, however, remains a problem. Because of this, future investigations are underway to combine chemotherapy with IORT, surgery and EBRT. The effectiveness of IORT needs to be established with prospective randomized trials. The appeal of this procedure is demonstrated by its rapidly growing popularity, and this very appeal requires that the value of the procedure be determined.

Biliary Tract Neoplasms

Rat liver tolerance for partial resection and intraoperative radiation therapy: regeneration is radiation dose dependent.

We studied the feasibility of delivering a large single dose of intraoperative radiation as an adjuvant to partial hepatic resection. Intraoperative radiation therapy (IORT) was delivered to the remaining liver of 84 rats after partial hepatectomy to determine the acute and chronic effects of treatment on blood chemistry values, histology, survival, hepatic regeneration, and cellular appearance of the normal liver. Transient elevations in SGOT, SGPT, and alkaline phosphatase were attributed both to hepatectomy and to liver parenchymal damage induced by IORT. Microscopic examination upon necropsy, performed at frequent intervals post-treatment revealed hepatic capsular thickening with some alteration of liver architecture mainly underneath the capsule, with localized inflammation and some areas of necrosis. Survival in all groups was 100% at 45 days. Liver weight increase proved to be dose-dependent and displayed a bisphasic pattern. This study demonstrated that IORT is a feasible adjunct to surgical resection of the liver in the rat model.

Alanine Transaminase

A pilot study investigating intraoperative electron beam irradiation in the treatment of ovarian malignancies.

Intraoperative electron beam radiation therapy (IOEBRT) in the treatment of ovarian malignancies was investigated at the Clement O. Miniger Radiation Oncology Center (COMROC). Nine patients were operated in the COMROC IOEBRT operating amphitheater and five were found to have disease sufficiently limited to allow for IOEBRT. The patients' ages ranged from 13 to 80 (median 53) years. Five patients had serous cystadenocarcinoma, one papillary adenocarcinoma, one mixed germ cell tumor, one squamous cell carcinoma, and one granular cell tumor of the ovary. The median survival of the non-IOEBRT group was 13 (range 12-29) months, while the IOEBRT group's median survival was 14 (range 18-46) months. All of the patients tolerated IOEBRT well without addition to the surgical morbidity.

Adenocarcinoma, Papillary

Radiation dose perturbation in the presence of permanent vascular-access injection ports.

Injection ports are commonly used to maintain permanent vascular access in patients with malignant disease. The injection ports allow blood sampling as well as infusion or injection of chemotherapeutic agents directly into the circulation. The access catheters are usually placed in the subclavian vein with the injection port being implanted in the intraclavicular area. These injection ports are entirely self-contained underneath the skin and may have been placed in an area which subsequently requires radiation treatment. A comprehensive study of the perturbation effects of the injection ports when placed in the path of the beam was carried out. All dose measurements were performed using stainless steel and titanium injection ports. The radiation beams were 6 MV and 10 MV X rays and 6, 9, 12, 15, and 18 MeV electrons. The data indicate that the presence of injection ports significantly alters the radiation dose and dose uniformity. For example, the dose underlying a stainless steel port is reduced by 47% when 18 MeV electrons are used. This paper presents the dosimetric data, discusses the clinical significance of the results, and provides recommendations for design modifications of the ports.

Catheters, Indwelling

Radiosurgical treatment compared to surgery alone for rectal cancer.

Between February 1981 and September 1989, 144 patients with rectal cancer were treated according to a radiosurgical sandwich protocol (27Gy + surgery + 18Gy) or postoperative radiotherapy (45Gy) at the University Hospital 'A. Gemelli' in Rome. This group is compared with a group of 133 patients operated on between January 1968 and January 1981, by the same team of surgeons but who received no radiotherapy. The historical group is comparable to the radiosurgical group in terms of stage, histology, and surgical procedures. The median follow-up period of the radiosurgical group is 38 months and 68% of cases have been observed longer than 2 years. At 2 years local recurrence in the historical control group was 22% versus 17% in the prospective group (p = 0.8). For Stage C disease, local recurrence dropped from 54% to 35% with adjuvant radiotherapy (p = 0.3). Metastases were observed in 22% of the control group versus 13% of the radiosurgical group (p = 0.2). For Stage C disease the incidence of distant metastases dropped from 59% to 26% at 2 years with the use of the prospective radiosurgical protocol (p = 0.05). The Kaplan-Meier survival rate at 5 years was 46% for the historical group and 72% for the radiosurgical group (p = 0.003) (Stage A 71% & 94%, Stage B 48% & 77%, and Stage C 16% & 38%, respectively). Neither serious nor late toxicity has been detected in the radiotherapy group, nor were surgical complications observed in the pre-operative radiotherapy group. The data strongly suggest a survival advantage for patients treated with the radiosurgical combination (p = 0.003).

Adenocarcinoma

Radiotherapy in the treatment of pancreatic cancer.

In the last two decades, we have witnessed revolutionary advances in pancreatic imaging as well as increased availability of megavoltage radiotherapy equipment and sophisticated radiotherapy planning devices. Several advances in the radiotherapy of pancreatic cancer have been made for the patient with resectable disease. Postoperative radiotherapy combined with chemotherapy confers a survival advantage after 'curative' resection. Preoperative and intraoperative intraoperative radiotherapy may do the same, but this requires further evaluation. Preoperative irradiation may improve the resectability rate, but the clinical data are still very limited. For locally unresectable disease, PHD radiotherapy with adjuvant 5-FU should now be the standard treatment in suitable cases with a median survival time of about one year. High LET radiation beams have failed to produce improved survival in two prospective randomized studies. Intraoperative radiotherapy is an effective means of pain control and enhances control of local disease, but has not been shown to improve survival rate significantly. Interstitial radiotherapy also improves local control, but it is associated with a high mortality rate and an even higher major complication rate. Wide-area radiation therapy and preoperative radiotherapy both seem to show promise in this group of patients. Patients with metastatic disease should be treated palliatively on an individual basis.

Combined Modality Therapy

Concomitant radiation therapy and constant infusion FUdR for unresectable hepatic metastases.

Ten patients with unresectable liver metastases from intraabdominal primary malignancies were treated with combined hepatic irradiation and hepatic artery infusion with FUdR using an Infusaid pump. The median survival for the entire group was 10 months. Four (40%) demonstrated an objective response to treatment: Three patients had a decrease in tumor mass on computed tomography (CT) scan, and one patient had a reduction in liver size as measured by palpation. The survival of two of the three patients whose tumor size was observed to be reduced on CT scan was significantly longer than that of the rest of the group (23, 37, and 12 months). Treatment was generally well tolerated with only mild side effects. Morbidity from chemotherapy did not appear to be enhanced by combination with hepatic irradiation. This form of treatment, although it has not demonstrated improved survival compared with other treatments in this setting, may be considered for adjuvant therapy in patients with hepatic metastases.

Abdominal Neoplasms

Aggressive therapy for cancer of the pancreas. Does it help?

Aggressive therapy clearly plays a role in the management of pancreatic cancer, be it localized to that organ, limited to the upper abdomen, or metastatic. A significant percentage of patients with resectable disease can be salvaged by radical resection of the cancer and aggressive adjuvant therapies. Five-year survival rates exceeding 30% have been reported from Japan. A supportive-care-only treatment philosophy ensures that almost all patients will die of cancer and that new treatment regimens will not be evaluated, creating a self-fulfilling prophecy. Such a policy is no longer tenable.

Adenocarcinoma