Ralph R. Dobelbower

Radiotherapy of unresectable pancreatic carcinoma: A six year experience with 104 patients☆☆☆

Abstract From 1974 to 1980, 104 patients with unresectable carcinoma of the pancreas were seen in the Department of Radiation Therapy at Thomas Jefferson University Hospital. Sixty-six patients were accepted for definitive therapy. Of these, 48 patients received precision high dose radiotherapy to a dose of 6800 rad on the 45 MeV Betatron, using either photons alone or mixed photon and high energy electron beams. Eighty-nine percent of the patients completed treatment as per the protocol. Relief of symptoms was obtained in 65 % of patients. Median survival was 10 months. In spite of the high doses employed, 67 % of the patients had evidence of recurrent tumor in the treatment volume at the time of death. In view of the high incidence of local failure with precision high dose therapy alone, a protocol using Iodine-125 implantation to supplement the external beam therapy was developed in 1978. Since then, 18 patients with disease confined to the region of the pancreas were treated with the combination of Iodine-125 implantation and precision high dose therapy. Eighty-five percent of the patients completed treatment. Follow-up ranges from eight to 22 months. None of the patients completing the treatment protocol have developed local recurrence of tumor. These results are presented together with details of the treatment technique, normal tissue reactions and implications for future approaches to the treatment of localized unresectable cancer of the pancreas.

Intraoperative radiation therapy of pancreatic carcinoma: A report of RTOG-8505

Abstract 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/m 2 /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 490. 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.

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.

125I interstitial implant, precision high‐dose external beam therapy, and 5‐FU for unresectable adenocarcinoma of pancreas and extrahepatic biliary tree

Twelve patients with adenocarcinoma of the pancreas and two patients with carcinoma of the extrahepatic biliary tree received combined therapy with 125I implant, precision high‐dose (PHD) photon external beam therapy, and systemic 5‐fluorouraciI (5‐FU). The 125I implant delivered 120 to 210 Gy (median 140 Gy). PhD external beam therapy was given with high‐energy photons (10, 15 or 45 meVp) and was initiated 4 to 6 weeks postimplant. A dose of 48.6 to 63 Gy was delivered over 5.5 to 7 weeks in 1.8 Gy increments. Six patients received 5‐FU, 500 mg/m2 via weekly intravenous bolus injection. No patient was lost to follow‐up (range, 3.5–57 months). Acute postoperative morbidity included pancreatic fistula in two patients and gastrointestinal tract bleeding, pulmonary embolism, and cholangitis in one patient each. No patient died of radiation complications. Median survival of the patients with pancreas cancer was 15 months. One patient is alive at 41 months with hepatic metastasis. Satisfactory palliation was observed in patients with pancreas cancer treated with 125I interstitial implant followed by PhD external beam photon therapy and 5‐FU. Patient survival did not seem superior to that of patients treated with PhD external beam therapy ± chemotherapy, a less morbid procedure. Two cases of bile duct cancer treated in similar fashion are presented.

Adjuvant radiation therapy for pancreatic cancer: A 15-Year experience

PURPOSE A retrospective analysis to determine differences in survival of patients with pancreatic adenocarcinoma treated by radical surgery with and without adjuvant radiation therapy. METHODS AND MATERIALS Between 1980 and 1995, 249 patients with pancreatic tumors were identified at the Medical College of Ohio. Forty-four of these patients underwent radical surgical procedures with curative intent. These patients were divided into four groups according to treatment: surgery alone (n = 14), surgery plus intraoperative radiation therapy (IORT) (n = 6), surgery plus external beam radiation therapy (EBRT) (n = 14), or surgery plus both IORT and EBRT (n = 10). Outcome and survival were analyzed among the four groups. RESULTS The median survival time of patients treated with radical surgery alone was 6.5 months. The median survival time for the surgery plus IORT group was 9 months; however, 33.3% (two of six) of these patients survived longer than 5 years. This survival pattern was borderline significantly better than that for the surgery alone group (p = 0.0765). The surgery plus EBRT and the surgery plus IORT and EBRT groups had median survival times of 14.5 and 17.5 months, respectively. These were significantly better than that of the surgery alone group (p = 0.0004 and p = 0.0002, respectively). The addition of radiation therapy did not affect the treatment complication rate. CONCLUSION The survival of patients who were treated with radical surgery alone was significantly poorer than that of patients who received adjuvant radiation therapy. These results are consistent with other studies in the literature. Patients treated with all three modalities (surgery, IORT, and EBRT) displayed the best median survival time.

Predictions of blood flow from thermal clearance during regional hyperthermia

In order to provide a method for estimation of regional blood flow during hyperthermia, a mathematical model has been developed which employs thermal clearance to measure this physiologic parameter. Limbs of mongrel dogs were heated with 2450 megaHertz microwaves to temperatures of 43 degrees C, 45 degrees C, or 47 degrees C and thermal washout was measured at five minute intervals throughout each treatment period. Calculated blood flow indicates that in response to heat challenge, normal tissue compensates by increasing regional blood flow within the treatment volume. This increase in blood flow continues to a maximum value after which the blood flow begins to decrease. Data indicate that the time for maximum increase in blood flow (induction time) decreases as treatment temperature increases. These induction times were 40 minutes, 25 minutes, and 15 minutes for treatment temperatures of 43 degrees, 45 degrees, and 47 degrees C, respectively. The data also show that the calculated value of peak blood flow is directly related to treatment temperature. Calculated peak blood flow values reached 37.8, 59.0, and 183.0 ml/minute/100 grams of tissue during 43 degrees, 45 degrees, and 47 degrees C, hyperthermia, respectively. It is suggested that a therapeutic advantage could be gained by treating tumors for a specific length of time during which the blood flow in adjacent normal tissues continues to increase. This would take maximum advantage of normal tissues ability to compensate for increased temperature, and would exploit any decreased ability of tumor tissue to perform this same function.

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).

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.

Inter-society standards for the performance of brachytherapy: a joint report from ABS, ACMP and ACRO

PURPOSE The proliferation of various brachytherapy modalities for different anatomical sites necessitates the creation of standards for brachytherapy. METHODS A panel consisting of members of The American Brachytherapy Society (ABS), The American College of Medical Physics (ACMP) and The American College of Radiation Oncology (ACRO) developed standards for the clinical practice and quality assurance (QA) of brachytherapy. These were based upon their clinical experience and a review of the literature. RESULTS Recommended practice standards are presented for clinical processes, treatment planning, equipment, facilities, QA, dose evaluation, dose specification, dose reporting, the training, and credentialing of personnel, and radiation control/safety/protection. Safe and efficacious performance of brachytherapy requires a highly structured QA program and carefully designed treatment delivery processes, as well as a coordinated effort amongst the team members. CONCLUSION Standards for clinical brachytherapy are proposed. Practitioners are encouraged to use these standards to design and implement a consistent and efficacious brachytherapy program.

Intraoperative radiation therapy

History of Intraoperative Radio Therapy. The Rationale for Intraoperative Radiotherapy. Radiobiology of Large Radiation Fractions. Application of Dose-Effect Relationships to Intraoperative Radiotherapy. Physical Aspects and Dosimetric Considerations for Intraoperative Radiation Therapy with Electron Beams. Physical Aspects of Intraoperative Radiation Therapy. Anesthesiologic Considerations for Intraoperative Radiation Therapy. Nursing and Technological Considerations in Intraoperative Radiation Therapy. The Development of an Intraoperative Radiation Therapy Program - The Groningen IORT Project. The Role of Orthovoltage Equipment for Intraoperative Radiation Therapy. The Use of Superficial X-Ray Equipment for Intraoperative Radiation Therapy. General Surgical Aspects of Intraoperative Radiation Therapy. Neurosurgical Considerations in Intraoperative Radiation Therapy. Intraoperative Radiation Therapy for Malignant Brain Tumors. Intraoperative Radiation Therapy for Advanced or Recurrent Head and Neck Malignancies. Intraoperative Radiation Therapy for Gastric Cancer. Intraoperative Radiation Therapy for Pancreatic Cancer in Japan. Intraoperative Radiation Therapy in Combination with Computer-Controlled Conformation Radiotherapy for Pancreatic Cancer. Intraoper-ative Radiation Therapy for Bladder Cancer. Intraoperative Radiation Therapy for Bladder Cancer: A Review of Techniques Allowing Improved Tumor Doses and Providing High Cure Rates Without the Loss of Bladder Function. Intraoperative Radiation Therapy for Prostatic Cancer. Intraoperative Electron Beam Radiation Therapy for Gynecological Malignancies. Intraoperative Radiation Therapy for Colorectal Cancer. Intraoperative Radiation Therapy of Soft Tissue Sarcomas. Intraoperative Radiation Therapy at the Massachusetts General Hospital. Mayo Clinic Experience with Intraoperative and External Beam Irradiation with or without Resection. The Rush-Presbyterian-St. Lukes Medical Center Experience with Intraoperative Radiation Therapy. Intraoperative Radiation Therapy: The Medical College of Ohio Experience. Participation of Community Facilities in Intraoperative Radiation Therapy. Intraoperative Radiation Therapy in Austria. Intraoperative Radiation Therapy in Spain: Clinical Experiences at the University Clinic of Navarra. The Economics of Intraoperative Radiation Therapy. Synopsis and Future Directions. Index.