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Biomedical subjects

R R Dobelbower

Publications and source records attributed to R R Dobelbower.

At least 37 records · Page 2Linked to original sources

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↗

Treatment of cancer of the pancreas by precision high dose (PHD) external photon beam and intraoperative electron beam therapy (IOEBT).

Twenty-five patients with a diagnosis of unresectable adenocarcinoma of the pancreas were explored in the Clement O. Miniger (COMROC) IOEBT operating amphitheater at the Medical College of Ohio. Seventeen were treated with IOEBT (20-30 Gy, 15 or 18 meV electrons) PHD external beam radiation therapy (40-60 Gy, 1.8 Gy per fraction) plus appropriate operative biliary and gastrointestinal bypass procedures. No intraoperative complications were observed. Two patients died of causes that may have been treatment-related. Two patients developed abdominocutaneous fistulae. Pain was ameliorated in eleven of twelve patients. Jaundice was relieved in all patients. Four of ten patients with weight loss showed a reversal of that trend. Patient survival was not significantly different from that of patients treated with high-dose precision therapy alone.

Adenocarcinoma↗

Treatment of cancer of the pancreas by intraoperative electron beam therapy: physical and biological aspects.

Radiation therapy has had a significant and an expanded role in the management of cancer of the pancreas during the last decade. In particular, for locally advanced disease, radiation therapy has improved the median survival of patients to 1 year. Intraoperative electron beam therapy has been applied to unresectable and resectable pancreatic cancer in an attempt to enhance local control of disease and to improve patient survival. This paper presents a survey of the role of radiation therapy in treatment of cancer of the pancreas, provides information on the radiobiological aspects of this treatment modality and details the physical and dosimetric characteristics of intraoperative radiation therapy with electrons. Presented are the design specifics of an applicator system, central axis beam data, applicator parameters, dose distribution data, shielding, treatment planning and means of verification. Emphasis is placed on the collaboration and cooperation necessary for all members of the intraoperative radiation therapy team including surgeons, radiation therapists, medical physicists, anesthesiologists, technologists, and nurses.

Cancer Care Facilities↗

Biochemical and cellular effects of radiofrequency induced interstitial hyperthermia on normal canine liver.

Interstitial hyperthermia (44.0 +/- 0.5 degrees C for 40 minutes) was delivered to the livers of 16 dogs to determine acute effects of treatment on blood chemistry, histology, and cellular appearance of normal liver. SGOT in treated animals peaked immediately at 300 +/- 21 U/L (within 2 hrs) and returned to control value within 7 days. LDH levels peaked at 1 day post-treatment and again at 2 weeks (300 +/- 16 U/L and 340 +/- 25 U/L respectively) and returned to pre-treatment values by week 4. SGPT remained elevated for 6 to 7 days following hyperthermia, but returned to control value at 2 weeks. There was also a rise in alkaline phosphatase (200 +/- 14 U/L 1 day post-treatment), which returned to a pre-treatment level by week 3. Changes in serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, lactate dehydrogenase, and alkaline phosphatase were attributed to both liver parenchymal damage induced by hyperthermia and to surgery. Other deviations in the blood chemistries and hematological parameters measured were ascribed to the stress response from surgical intervention, or to the resultant hemodilution from fluids during surgery. Microscopic examination upon necropsy, performed 4 weeks post-operatively, displayed limited fibrosis with some alteration of liver architecture, generalized sinusoidal dilation and red blood cells in the space of Disse. Cellular ultrastructure changes showed an increase of myelin figures, but mitochondria and other cellular organelles remained essentially normal. Localized tissue inflammation and some loss of function occurred in response to localized hyperthermia for this volume of tissue at therapeutic temperatures. This study showed that the technique was feasible and confirmed that the parenchymal damage caused by interstitial hyperthermia did not produce the severe loss of function that might have been expected.

Alanine Transaminase↗

Intraoperative interstitial hyperthermia in conjunction with intraoperative radiation therapy in a radiation-resistant carcinoma of the abdomen: report on the feasibility of a new technique.

The application of a new technique of intraoperative interstitial hyperthermia (IOHT) and intraoperative radiation therapy (IORT) was investigated for unresectable abdominal carcinoma. A 43-year-old white male presented with severe back pain due to metastatic adenocarcinoma in the left paravertebral area, producing erosion of the body of T12. The disease had not responded to external beam radiation therapy. The tumor was approached through a thoraco-abdominal incision and IOHT was delivered via interstitial electrodes. Temperature was monitored at 16 locations within the tumor. An LCF hyperthermia unit was utilized to deliver RF power and produced a treatment temperature of 43 degrees C for 60 minutes uniformly throughout the treatment volume. Immediately following hyperthermia treatment, the lesion was treated with 15 meV electrons via IORT to a tumor dose of 25Gy. The patient recovered without complication and had complete relief from pain. Posttreatment CT scans have demonstrated control of disease over a 5-month follow-up period. A clinical pilot study has been established to further investigate the application of this combination therapy.

Adenocarcinoma↗

Modified mesh panel for radiation therapy treatment table.

The design and construction of a mesh panel for radiation therapy treatment tables is described. With the new design, sagging is virtually eliminated. The panels have been successfully used for a variety of patient sizes and weights.

Radiotherapy↗