In vivo tendon forces correlate with activity level and remain bounded: evidence in a rabbit flexor tendon model

The purpose of this study is to assess the feasibility, clinical tolerance, local control, and survival rates using a combined-modality treatment program of intraoperative radiation, chemotherapy, and external beam radiation for the management of patients with pancreatic cancer. One hundred eighty patients with biopsy-proven adenocarcinoma of the pancreas have been treated by a single surgical practice between 1979 and 1992. Of these, 105 had locally advanced but unresectable primary tumors (stages 2 and 3). All patients were treated with a program of multimodality therapy, including surgery, chemotherapy, and radiation therapy. Three groups were identified. Group I (33 patients) received intraoperative radiation therapy (IORT) as part of their treatment. Group II (43 patients) received intraoperative radiation in the form of iodine-125 (I-125) implantation. Group III (29 patients) received no intraoperative radiation. All three groups were comparably similar with respect to age at presentation, amount of preoperative weight loss, preoperative symptoms, and tumor location. Overall perioperative mortality was 4.8 per cent (five patients), with no difference between groups noted. Perioperative complications occurred in 32 (30.4%) of the 105 patients. Complications occurred in only 18.1 per cent of patients in Group I (IORT), compared with 39.5 per cent of Group II (I-125) patients (P < 0.01). Group III patients (no intraoperative radiation) experienced complications in 31.0 per cent of cases (P = 0.09 vs Group I). Actuarial survival was 18 months for Group I (IORT) versus 15 months for Group II (I-125). One- and 2-year actuarial survival rates were 60 and 17 per cent for patients in Group I (IORT) and 56 and 19 per cent for Group II (I-125). Actuarial local control rates for patients receiving IORT (Group I) was 70 per cent at 2 years. Patients with pancreatic cancer historically have poor survival and local control rates despite aggressive chemotherapy and radiation. The addition of intraoperative radiation to the combined modality management of pancreatic cancer offers markedly improved survival rates and local control with minimal morbidity for patients with unresectable disease. Intraoperative radiation in the form of IORT can be delivered with a significantly fewer complications than I-125 seed implantation.     

Intraoperative radiotherapy for pancreatic carcinoma with hepatic or peritoneal metastases

BACKGROUND/AIMS: The purpose of this study was to determine the efficacy of intraoperative radiotherapy (IORT) for unresectable pancreatic carcinoma associated with hepatic or peritoneal metastasis. METHODOLOGY: Between 1991 and 1994, 53 patients with pancreatic carcinoma associated with hepatic or peritoneal metastasis underwent surgery. Twenty-four of these patients received IORT, while 29 received no radiation therapy. The efficacy of IORT on the postoperative survival and pain relief for these patients was retrospectively analyzed. RESULTS: Postoperative survival was lowest in the subgroup of patients (n = 18) with both hepatic and peritoneal metastases, and this group did not benefit from IORT (IORT, n = 6; no IORT, n = 12) in terms of survival. Similarly, there was no significant difference in the survival rates between patients undergoing IORT (n = 10) and patients without IORT (n = 11) in the subgroup of patients with hepatic metastasis but without peritoneal metastasis. However, patients with peritoneal metastasis but without hepatic metastasis benefited significantly from IORT (IORT, n = 8; no IORT, n = 6) (p < 0.05). Pain relief following IORT was observed in 9 out of 10 patients who had experienced pain prior to surgery. CONCLUSION: Pancreatic carcinoma associated with peritoneal metastasis but without hepatic metastasis can be palliated by IORT. In addition, pain palliation in patients who require gastrointestinal or biliary drainage can also be achieved by IORT.     

Intraoperative radiotherapy of unresectable pancreatic carcinoma

During the period from 1986 to 1991, 33 patients with unresectable carcinoma of the pancreas received intraoperative radiotherapy (IORT). Abdominal and back pain which tormented all patients before IORT totally disappeared in 18 patients (54%) and was allevrited in 13 patients (40%). The average survival time of 6.5 months for patients treated with IORT was not statistically different from that of 30 patients with resectable pancreatic cancers undergoing resection. IORT hence is a good palliative therapy for unresectable carcinoma of the pancreas.     

Effect of rodents on reforestation in the moumtain regions near Beijing

A long survival is rarely observed in patients demonstrating recurrent malignant lymphoma with bulky disease because of the appearance of chemoresistant tumor cells after extensive chemotherapy, and moreover the presence of bulky disease has also been consistently associated with a poorer response rate and a shortened survival, due to the fact that tumor size is the most significant factor for the treatment of non-Hodgkin's lymphoma. We herein describe a case of a 53-year-old woman presenting with the chief complaint of abdominal fullness, who underwent intraoperative radiation therapy (IORT) for recurrent bulky non-Hodgkin's lymphoma in the mesenterium. The patient has had no evidence of tumor recurrence, based on the findings of regular abdominal computed tomographic scans, 60 months after initial chemotherapy and 28 months after IORT.     

Beagle model used in a tissue tolerance study of the response of normal and surgically manipulated liver to single high-dose intraoperative radiotherapy

To investigate the feasibility of delivering a single large dose of intraoperative electron beam radiotherapy (IORT) to the liver of clinically normal and partially hepatectomized beagles, an experimental study was designed. The purpose of the study was to obtain dose guidelines for the delivery of IORT to the liver of human patients with colorectal cancer metastases to the liver. After partial resection of the liver, IORT in doses up to 30 Gy was applied to the resection plane as well as to a nonsurgically manipulated part of the liver of 25 beagles. The temporal sequence of histologic changes of these irradiated parts of the liver tissue was investigated. There were no postoperative complications and no morbidity or mortality associated with a minimal follow-up of 3 years. Necropsy performed 3 months after IORT revealed only mild histopathologic changes. One year after IORT, more distinct histopathologic changes consisting of capsular thickening, diffuse parenchymal fibrosis, and subcapsular hepatocellular atrophy were found. Three years after IORT, the parenchymal architecture seemed to be restored, although loss of liver tissue was definitive at the irradiation site; liver function remained intact. These results indicate that IORT to part of the liver in the canine model can be safely applied and that, although doses up to 30 Gy can result in severe local tissue damage, wound healing and liver function are not disturbed.     

The current status of intraoperative radiotherapy in colorectal surgery

Colorectal cancer is the second most common malignancy in Singapore and its incidence is increasing. Results of surgery have been augmented in selected cases by the addition of radiotherapy and chemotherapy. This standard approach only offers palliation in locally advanced and locally recurrent cancers. Newer modalities and combinations are currently being investigated to improve the results in this particular group of patients. One such modality is the use of intraoperative radiotherapy (IORT). This paper discusses the rationale for using IORT, the patient selection, method of delivery and treatment, tolerance and results in centers which have been using IORT as part of a multi-modality therapy for colorectal cancer.     

Intra-operative radiation therapy in pediatric neuroblastoma

External beam irradiation (EBRT) has been shown to improve response rates and event-free survival in children with neuroblastoma and regional lymph node metastases. Irradiation during surgical exposure (intra-operative radiotherapy, IORT) with displacement of adjacent radiosensitive organs out of the treatment field allows for more precise delineation of the target volume and significantly reduces the amount of normal tissue exposed to irradiation. We have incorporated IORT into the treatment regimen of 24 children with neuroblastoma between the years of 1983-1991. IORT was directed to any residual tumor or the tumor bed; the median dose of radiation was 1,000 cGY, equivalent to 3,000 cGY of conventional EBRT. There were 11 males and 13 females. Two patients had stage II, 12 patients had stage III, and 10 patients had stage IV disease. Ten children received IORT for suspected recurrent or persistent neuroblastoma. Twelve patients were disease-free survivors following IORT with a median follow-up of 54 months. For those patients with stage III disease, seven children were disease-free survivors, while only three of 10 patients with stage IV disease survived (median follow-up 30 months). Disease-free Survival (DFS) correlated with the achievement of local tumor control in children with both stage III and IV neuroblastoma. There was limited morbidity and no episodes of obstructive uropathy were encountered. We conclude that IORT appears to be well tolerated and may have therapeutic benefit for a select group of patients with neuroblastoma. IORT merits future exploration by prospective study.     

Mediterranean mysteries: mechanisms of declining alcohol consumption

The efficacy of intraoperative radiotherapy (IORT) for the local recurrence of rectal cancer was evaluated. Operations were performed for a total of 43 patients with local recurrence of rectal cancer, and among them 13 cases received IORT. These patients were divided into two groups those with a suspicion of cancer remaining in the surgical margin macroscopically (EW+ group) or those with no such suspicion (EW- group). The length of pain relieving period and total survival between the IORT and no IORT groups in EW- patients showed no statistical difference. Though the same result was found in EW+ patients, in the patients whose area of positive surgical margin was less than 10 cm2 and given IORT, the pain relief period was prolonged compared with the no IORT patients such as 270 days v.s. 218 days. IORT did not show efficacy in terms of the survival period, but if the local remnant area was small, it was beneficial for the patients in terms of the pain period.     

Intraoperative radiotherapy in gastrointestinal tumors

Intraoperative radiotherapy has proved its worth for curative and palliative treatment of gastrointestinal tumors. IORT indications comprise cancer of the stomach, of the pancreas and colorectal carcinomas. Most authors are cautious to apply it to carcinoma of the esophagus, of the small intestine and of the hepatobiliary system. IORT is applied as adjuvant treatment alone or in combination with postoperative external-beam photon irradiation +/- chemotherapy. There is evidence of an improved local control rate. Pain can be relieved in symptomatic patients by an IORT dose of > or = 20 Gy. Until now, however, there is no evidence of a prolonged relapse-free and overall survival.     

Autologous bone marrow transplantation in children with advanced neuroblastoma

BACKGROUND: Encouraging results have been reported with high dose chemotherapy and total body radiation followed by bone marrow autotransplantation in children with advanced neuroblastoma; however, relapse remains a significant problem. METHODS: The authors treated 22 children with advanced neuroblastoma with high dose chemotherapy, surgery, intraoperative radiation, and a bone marrow autotransplant (treated in vitro to remove tumor cells) followed by 13-cis-retinoic acid. RESULTS: The 3-year relapse rate was 25% (95% confidence interval [CI], 6-44%). The 3-year disease free survival rate was 72% (95% CI, 52-92%). Toxicities included hemolytic uremic syndrome, herpes infection, and hepatic venoocclusive disease. CONCLUSION: These data suggest that this treatment strategy offers an increased rate of 3-year disease free survival. The nonrandomized nature of this study and its use of multiple modalities precludes the analysis of the specific contribution of each treatment component and comparison with conventional therapy.     

Intraoperative radiotherapy. Literature updating with an overview of results presented at the 6th International Symposium of Intraoperative Radiation Therapy

Intraoperative radiotherapy is a technique that can be integrated into multidisciplinary treatment strategies in oncology. A radiation boost delivered with high energy electron beams can intensify locoregional antitumor therapy in patients undergoing cancer surgery. Intraoperative radiotherapy can increase the therapeutic index of the conventional combination of surgery and radiotherapy by improving the precision of radiation dose location, while decreasing the normal tissue damage in mobile structures and enhancing the biological effect of radiation when combined with surgical debulking. Intraoperative radiotherapy has been extensively investigated in clinical oncology in the last 15 years. Commercially available linear accelerators require minimal changes to be suitable for intraoperative radiotherapy. Its successful implementation in clinical protocols depends on the support given by the single institutions and on a clinical research-oriented mentality. Tumors where intraoperative radiotherapy as a treatment component has shown promising rates of local control include locally advanced rectal, gastric and gynecologic cancer, bone and soft tissue sarcoma. Intraoperative radiotherapy can be applied to brain tumors, head and neck cancer, NSCLC and pancreatic carcinoma.     

Intraoperative radiotherapy combined with external beam radiation for prostate cancer without metastasis

Between 1989 and 1996, 35 patients with prostate cancer without metastasis received intraoperative radiotherapy combined with external beam radiation. 10 of 16 stage B patients and all of 19 stage C patients received additional endocrine therapy for the initial treatment. The radiation therapy included 25-30 Gy of intraoperative radiotherapy for prostate and 30 Gy of external beam radiotherapy for small pelvic region. One patient of stage C was dead for cancer and 4 patient were dead for other causes during 15-99 (mean: 41.6) months follow up period. The overall actuarial survival at 5 years by Kaplan-Meier method were 92.3% for stage B and 87.2% for stage C. Although cystitis, proctitis and anal bleeding were observed as the adverse effects of radiotherapy, both acute and chronic symptoms were not critical. In conclusion, intraoperative radiotherapy combined with external beam radiotherapy was revealed as an effective treatment for prostate cancer without metastasis.     

Pelvic radiation therapy as a risk factor for ischemic colitis complicating abdominal aortic reconstruction

Ischemic colitis is an infrequent but potentially devastating complication of abdominal aortic reconstruction. Identification of patients with predisposing risk factors for the development of ischemic colitis can guide intraoperative measures to preserve or restore colonic blood flow during aortic surgery. Previous radiation therapy for pelvic malignancy may be one such predisposing risk factor. Two cases are presented in which ischemic colitis complicated abdominal aortic reconstruction in the setting of previous pelvic irradiation. In the months after radiation therapy for prostate cancer, one patient underwent infrarenal abdominal aortic aneurysm repair. Ischemic infarction of the sigmoid colon developed acutely after surgery and required emergent sigmoid colectomy. The second patient underwent reconstruction of an infrarenal abdominal aortic aneurysm after having had radiation therapy for a bladder tumor. Despite an initial satisfactory result, the patient's abdominal pain and diarrhea progressively worsened and he eventually required sigmoid colectomy for severe ischemic colitis. In both of these patients, the inferior mesenteric arteries were patent and had not been reimplanted. The association of pelvic radiation therapy with ischemic colitis after aortic reconstruction should focus attention to the operative details for maintaining the colonic circulation in these patients. Reimplantation of the inferior mesenteric artery in particular may prevent both the acute and the insidious variants of this complication in patients who undergo aortic surgery and decrease the incidence of this complication in patients with a history of radiation therapy to the pelvis.     

The use of diode dosimetry in quality improvement of patient care in radiation therapy

The purpose of this work is to improve the quality of patient care in radiation therapy by implementing a comprehensive quality assurance (QA) program aiming to enhance patient in vivo dosimetry on a routine basis. The characteristics of two commercially available semi-conductor diode dosimetry systems were evaluated. The diodes were calibrated relative to an ionization chamber-electrometer system with calibrations traceable to the National Institute of Standards and Technology (NIST). Correction factors of clinical relevance were quantified to convert the diode readings into patient dose. The results of dose measurements on 6 patients undergoing external beam radiation therapy for carcinoma of the prostate on three different therapy units are presented. Field shaping during treatments was accomplished either by multileaf collimation or by cerrobend blocking. A deviation of less than +/-4% between the measured and prescribed patient doses was observed. The results indicate that the diodes exhibit excellent linearity, dose reproducibility, minimal anisotropy, and can be used with confidence for patient dose verification. Furthermore, diodes render real time verification of dose delivered to patients.     

Validation of serum transthyretin (prealbumin) as a nutritional parameter in hemodialysis patients

Discoloring of glass due to ionizing radiation depends on the absorbed dose. The radiation-induced light attenuation in optical fibers may be used as a measure of the dose. In high-energy photon beams (6 MV X rays), a lead-doped silica fiber can be calibrated. A dosimeter based on an optical fiber was developed for applications in radiation therapy. The diameter of the mounted fiber is 0.25 mm, whereas the length depends on the sensitivity required. To demonstrate the applicability, a customized fiber device was used to determine scattered radiation close to the lens of the eye. Measurements were compared with TLDs (LiF) in an anthropomorphic phantom. The comparison with TLD measurements shows good agreement. In contrast to TLD, optical fibers provide immediate dose values, and the readout procedure is much easier. Owing to its small size and diameter, interesting invasive dose measurements are feasible.     

Radiation therapy for malignant melanoma

Sufficient biologic and clinical evidence now exists to refute the longstanding dogma that melanomas are uniformly radiation resistant and hence radiation therapy has little role in the management of this disease. Although surgery remains the treatment of choice for the vast majority of localized melanomas, available data indicate that radiation therapy is a viable alternative for a few subsets of patients in whom surgery would result in cosmetic or functional deformity, such as patients with large facial lentigo maligna melanomas or small or intermediate-sized uveal melanomas. Retrospective and Phase II prospective studies have revealed that elective/adjunctive radiation therapy improves the local-regional control rate in patients with thick primary lesions, nodal involvement, or mucosal melanomas. However, the impact of elective/adjunctive radiation therapy on the survival rate has yet to be determined. Radiation therapy has been established as a simple and cost-effective treatment modality for palliation of patients with symptomatic metastatic spread. The response of metastatic deposits to radiation varies with the tumor volume, total dose, and dose per fraction. The choice of optimal fractionation depends on tumor site and the patient's survival expectation. New data indicate that hyperthermia enhances the response of metastatic lesions to radiation. Ongoing research with a variety of experimental strategies may offer the possibility of further increasing the utility of radiation therapy in the management of this disease.     

Radiotherapeutic management of cervical carcinoma that complicates pregnancy

BACKGROUND: Data regarding radiation therapy for pregnant patients with cervical carcinoma are limited. The goal of this study was to assess the effects of pregnancy on tumor control, survival, and morbidity associated with radiation therapy administered to pregnant patients. METHODS: The authors performed a retrospective case-control analysis of 26 women with cervical carcinoma who were diagnosed during pregnancy and treated primarily with radiation therapy. These cases were matched with 26 controls based on age, histology, stage, treatment, and year of treatment. RESULTS: Patients were treated with external beam radiation (mean dose, 46.7 gray [Gy]) and intracavitary radiation (mean dose, 56.5 Gy to Point A). Two patients with Stage IA2 squamous cell carcinoma treated in the third trimester had a planned delay in treatment of 3 weeks, and both infants had an uncomplicated neonatal course. Seven pregnant patients (2 Stage IB1, 5 Stage IB2) underwent radiation after radical hysterectomy was aborted due to positive regional lymph nodes. Three patients diagnosed during the first trimester were treated with radiation with the fetus in situ, and all had spontaneous abortions 20-24 days after the start of radiation (mean dose, 34 Gy). In all these cases, radiation was interrupted for only 3 days or less. There were no statistically significant differences in recurrence rates or survival between the pregnant group and the controls. Short term toxicity was comparable in pregnant and nonpregnant patients and easily controlled. Long term complications were more common in controls (12% in pregnant patients, 27% in controls), but this difference was not statistically significant. Most complications were likely related to radiation techniques (particularly the predominance of cobalt-60). CONCLUSIONS: Planned delay in treatment should be offered to pregnant patients with early stage squamous cell carcinoma in the late second and early third trimester. Patients diagnosed in the first or second trimester who are not good candidates for planned delay in treatment should be given radiation therapy immediately. It may be necessary to reconsider planned radical hysterectomy for pregnant women with Stage IB2 disease due to the high rate of lymph node positivity found on exploration. For patients with advanced disease, radiation therapy appears to be a safe and effective modality.     

Differential effects of N-methyl-D-aspartate receptor blockade on nociceptive somatic and visceral reflexes

OBJECTIVE: A Phase I study was conducted to determine the safety, toxicity, and maximum tolerated dose of preirradiation chemotherapy using carmustine (BCNU) and cisplatin in the treatment of high-grade gliomas. METHODS: Patients with newly diagnosed high-grade gliomas received BCNU and cisplatin after surgery, both before and during definitive radiation therapy. Preirradiation chemotherapy consisted of an administration of 40 mg/m2 BCNU on Days 1 through 3 and 30 mg/m2 cisplatin on Days 1 through 3 and 29 through 31 and repeated at 8 weeks to coincide with the start of radiation therapy. Postradiation chemotherapy consisted of an administration of 200 mg/m2 BCNU once every 8 weeks for four cycles. Radiation therapy consisted of 160-cGy fractions administered twice daily for 15 days, yielding a total dose of 4800 cGy. Dose escalation of BCNU was planned. If hematological toxicity was mild, the dose of cisplatin was to be held constant and BCNU dose escalated to 50 mg/m2 on Days 1 through 3. RESULTS: Eighteen patients were studied. The hematological toxicity was dose-limiting. Grade 3 or 4 leukopenia occurred in each of 10 patients (56%), and Grade 3 or 4 thrombocytopenia occurred in each of 9 patients (50%). Other toxicities included anorexia (94%), nausea (83%), emesis (33%), alopecia (94%), mild ototoxicity (50%), and, in one patient, death as a result of BCNU pulmonary toxicity. The median survival time was 14 months. Objective responses occurred in 45% of the patients evaluable for response. The maximum tolerated dose of this combination was 50 mg/m2 BCNU on Days 1 through 3 and 30 mg/m2 cisplatin on Days 1 through 3 and 29 through 31 before radiation and repeated in 8 weeks to coincide with the start of radiation. CONCLUSION: This schedule of the preirradiation administration of BCNU and cisplatin with accelerated hyper-fractionated radiation therapy for the treatment of high-grade gliomas provides a less toxic alternative to that of previous studies of preirradiation chemotherapy with these agents and merits further investigation.