Autopsy verifies demyelination and lack of vascular damage in partially reversible radiation myelopathy.

STUDY DESIGN: Case report of recovering radiation myelopathy. OBJECTIVE: To present autopsy and functional imaging findings on a unique case of slowly recovering radiation myelopathy with the aim of the clarification of the underlying mechanism. PATIENT: The cervical spinal cord and the distal part of the medulla oblongata of a 36-year-old thyroid cancer patient had been incorrectly irradiated with a total dose of 61 Gy and a fraction size of 3.4 Gy (J Neurol Sci 1999; 163:39-43), resulting in incomplete cervical transection with a 5-month latency period following the termination of radiotherapy. This was followed by a 9.5-year spontaneous improvement until her demise, during which the check-ups were supplemented by positron emission tomography (PET) investigations; these indicated increased [18F]deoxyglucose and [15O]butanol uptakes, but a diminished [11C]methionine accumulation by the irradiated spinal cord segment. RESULTS: Autopsy revealed demyelination (with axonal loss) and neuronal damage in the cervical spinal cord and the distal part of the medulla oblongata. In the same region, only minimal vascular injury (thickening of some of the capillary walls) was detected, but not cell proliferation or chronic inflammation. Bilateral, secondary pyramidal tract degeneration caudal to the irradiated segment was observed. The PET and autopsy findings, although separated by 2 years, are consistent. CONCLUSIONS: The pathological state of the spinal cord revealed by the autopsy is concordant with the incomplete cervical transection, implying that the functional recovery is supported by a process that probably differs from the restoration of the mechanism destroyed by the radiotherapy. For the restoration of the function, we suggest an altered conduction mechanism of the action potential, involving an increased number of sodium channels along the demyelinated segments of the injured axons, which is fully congruent with the PET findings.

Intracoronary radiation with gamma wire inhibits recurrent in-stent restenosis.

To study the safety and efficacy of intracoronary gamma radiation delivered via a new high-activity (192)Ir source wire for the treatment of in-stent restenosis. In-stent restenosis results from neointimal tissue proliferation especially in its diffused form and presents a therapeutic challenge. Gamma radiation has been shown to decrease neointima formation within stents in animal models and in initial clinical trials. A total of 26 patients with in-stent restenosis underwent successful intervention and was treated with open-label (192)Ir using a high-activity line source. The specific activity of the source wire was 372+/-51 mCi, and the dwell time was 10.8+/-1.9 min. Primary endpoints were freedom from death, myocardial infraction (MI), and repeat target lesion revascularization (TLR) at 6 months. Secondary endpoints included angiographic restenosis and intravascular ultrasound (IVUS) neointimal hyperplasia. Procedural success was high (96.2%), and in-hospital and 30-day complications were low with no deaths, MI, or requirement for repeat revascularization. At 6 months, event-free survival was 85%: one patient required repeat PTCA, one underwent bypass surgery, and two had an MI. Baseline lesion length measured 15.77 mm. Follow-up angiography was available in 21/25 (84%) patients. The binary restenosis rates were 19.0% (4/21) in-stent and 23.8% (5/21) in-lesion. Follow-up IVUS was available in 20/25 patients. There was no increase in intimal hyperplasia from postintervention to follow-up (3.11.8 vs. 3.41.8 mm(2); P=.32). Eight patients had a reduction of neointimal intimal tissue at follow-up. These results indicate that intracoronary gamma radiation with the Angiorad source wire is safe and effective in preventing in-stent restenosis.

Treatment planning dosimetric parameters for a (90)Y coil source used in intravascular brachytherapy.

BACKGROUND: (90)Y coil sources have been used in animal and clinical trials for treatment of restenosis in intravascular brachytherapy (IVBT). This study aims to determine the American Association of Physicists in Medicine (AAPM) Task Group-60 (TG-60) dosimetric quantities in regions surrounding the balloon wall for use in treatment planning computer systems. METHODS: The Monte Carlo method was used to determine the dose distribution, using MCNP4B2 code. The coil source was modeled by a hollow cylinder of 2.9 cm length centered in a balloon (2.5 mm diameter) filled with carbon dioxide (CO(2)) at 5 atm. Scoring voxels consisted of contiguous annular disk shells with 0.1 mm spacing in the radial direction and 0.2 mm spacing in the longitudinal direction. The scoring region ranges from the center of the source to 1.0 cm in the longitudinal direction, and from 0.13 to 1 cm in the radial direction. In the plane containing the source axis, the Monte Carlo-generated doses in rectilinear coordinates are converted to polar coordinates. RESULTS: The dose rate of the source is provided in both Cartesian and polar coordinates. The dose rate constant [D(r(0),theta(0))], anisotropy function [F(r,theta)], and radial dose function [g(r)] were generated from these values and listed in tabular format. At shallow angles and longer distances from the source center, large values of the anisotropy function resulted, deviating two orders of magnitude from unity. CONCLUSIONS The doses given to the intima, media, and adventitia are very crucial quantities in IVBT. The calculated TG-60 dosimetric quantities, used commonly in conventional brachytherapy applications, provide a means for the user to determine the three-dimensional dose surrounding the balloon catheter. These parameters can be used in future treatment planning system for IVBT. We also discuss the need to develop a new formalism specific to longer sources used in IVBT.

Effect of stent on radiation dosimetry in an in-stent restenosis model.

Purpose: Intravascular brachytherapy is the leading modality being evaluated for treatment of in-stent restenosis. Stent struts may have an effect on the dose distributions of various radiation sources. We evaluated dosimetry in a stented coronary artery model using a variety of beta and gamma sources and stent materials.Methods: We determined the dose distributions with and without stent in the in-stent restenosis model. Three beta-particle emitting radionuclides, 90Y (2.3 MeV), 144Pr (3.0 MeV), and 106Rh (3.5 MeV), and two gamma-ray emitters, 192Ir (380 keV) and 125I (30 keV), were studied. Stent materials included stainless steel, nitinol, and tantalum. Monte Carlo dose calculations were performed in a stent model of multiple stent struts placed at 1.5 mm from the source. Isodose curves were generated and the ratios of dose rates with and without stent, the stent factors, were evaluated. A stent factor of greater or less than unity represents dose enhancement or reduction in the presence of a stent.Results: For the three beta radionuclides, dose reduction was found on the adventitial side of the stent strut and dose enhancement was noted on the luminal side. On the luminal side, the maximum dose enhancement ranges from 7% to 29%, and the dose reduction on the adventitial side ranges from 13% to 43%. Both the reduction and enhancement effects were most pronounced for the high atomic number material, tantalum. For a given stent material, the dose reduction and enhancement are similar for the three beta radionuclides. For the gamma sources, the stent had no effect for the high-energy 192Ir, but for the low-energy 125I, drastic dose reduction on the adventitial side was observed (up to 86% for tantalum stent), and about 10% dose enhancement on the luminal side was also noted. The dose reduction with 125I was more pronounced than that seen with the beta sources.Conclusions: The presence of stent struts significantly affects dose distributions of 90Y, 106Rh, 144Pr, and 125I. The maximum dose reduction can be as much as 86%. 192Ir was unaffected. These factors need to be considered in choosing radionuclides and dose prescriptions in treating in-stent restenosis.

Ytterbium-169: a promising new radionuclide for intravascular brachytherapy.

PURPOSE: To explore the feasibility of 169Yb (gamma, 93 keV) as a new radionuclide for intravascular brachytherapy (IVBT) in terms of dose distribution, penetration power, and radiation safety features as compared with 125I and 192Ir. METHODS: The dose distributions for catheter-based sources, 169Yb, 125I, and 192Ir, in homogeneous water and in the presence of calcium and a steel stent have been determined and compared using the Monte Carlo method (MCNP4B2 code). The dose rates of the sources were evaluated from 0.02 to 100 cm. RESULTS: In the short distance range (0.02

Effect of stent on radiation dosimetry in an in-stent restenosis model.

PURPOSE: Intravascular brachytherapy is the leading modality being evaluated for treatment of in-stent restenosis. Stent struts may have an effect on the dose distributions of various radiation sources. We evaluated dosimetry in a stented coronary artery model using a variety of beta and gamma sources and stent materials. METHODS: We determined the dose distributions with and without stent in the in-stent restenosis model. Three beta-particle emitting radionuclides, 90Y (2.3 MeV), 144Pr (3.0 MeV), and 106Rh (3.5 MeV), and two gamma-ray emitters, 192Ir (380 keV) and 125I (30 keV), were studied. Stent materials included stainless steel, nitinol, and tantalum. Monte Carlo dose calculations were performed in a stent model of multiple stent struts placed at 1.5 mm from the source. Isodose curves were generated and the ratios of dose rates with and without stent, the stent factors, were evaluated. A stent factor of greater or less than unity represents dose enhancement or reduction in the presence of a stent. RESULTS: For the three beta radionuclides, dose reduction was found on the adventitial side of the stent strut and dose enhancement was noted on the luminal side. On the luminal side, the maximum dose enhancement ranges from 7% to 29%, and the dose reduction on the adventitial side ranges from 13% to 43%. Both the reduction and enhancement effects were most pronounced for the high atomic number material, tantalum. For a given stent material, the dose reduction and enhancement are similar for the three beta radionuclides. For the gamma sources, the stent had no effect for the high-energy 192Ir, but for the low-energy 125I, drastic dose reduction on the adventitial side was observed (up to 86% for tantalum stent), and about 10% dose enhancement on the luminal side was also noted. The dose reduction with 125I was more pronounced than that seen with the beta sources. CONCLUSIONS: The presence of stent struts significantly affects dose distributions of 90Y, 106Rh, 144Pr, and 125I. The maximum dose reduction can be as much as 86%. 192Ir was unaffected. These factors need to be considered in choosing radionuclides and dose prescriptions in treating in-stent restenosis.

Surgical treatment of non-small cell lung cancer in patients older than seventy years.

Surgical treatment of non-small cell lung cancer has been reported to be associated with increased mortality, especially when pneumonectomy has been employed. A 9-year review of 81 patients treated surgically, with a policy of avoiding pneumonectomy and using internal radiation and wedge excisions rather than lobectomy among patients with impaired reserve, resulted in an operative mortality of 4.9% compared with an overall mortality of 2.1%. Three of the four deaths were among patients older than 80 3/17 (17.6%) years so that mortality of patients 70 < age < 80 was not significantly different from overall mortality. Two of the four deaths were related to pulmonary emboli but there have been no such deaths since routine use of mini-heparin was initiated in 1990. Five-year survival was 42% overall, 65% for stage 1, and 24% for stages II-IIIB. We conclude that surgical treatment of patients 70 < age < 80 may be accomplished with similar mortality and survival as the overall population. Heparin prophylaxis may be especially important among patients older than 80 years.

Chemoradiation in advanced nonsmall cell lung cancer.

PURPOSE: Resectability, local control, and survival were evaluated in advanced stage nonsmall cell lung cancer treated with simultaneous chemoradiation therapy delivered in an accelerated, interrupted twice-a-day schedule. METHODS AND MATERIALS: Forty-seven consecutive patients with Stage IIIA or IIIB nonsmall cell lung cancer, consenting to participation in the study, received cisplatin, 30 mg/m2 for 3 days, etoposid, 80 mg/m2 for 3 days, and 5-fluorouracil, 900 mg/m2 for 4 days. Radiation therapy consisted of 2 Gy given twice a day for 5 days. Two weeks rest was planned between cycles. Patients were evaluated for resectability after the second cycle. Any patient with unresectable tumor received a third cycle of treatment. RESULTS: Forty-seven patients were evaluable for acute toxicity: eighteen (38%) required an extended rest period for esophagitis or low blood count; 3 (6%) had sepsis, of whom 1 (2%) expired. Three patients (6%) had multiple blood transfusions for low hemoglobin. Median follow-up is 23.6 months, with a range of 10-49 months. Nine patients (19%) failed locally; 15 (32%) had local and distant failure; 7 (15%) failed only at distant sites. Twelve patients (25.5%) are alive with no evidence of disease; 4 patients were lost to follow-up with disease. The 2-year actuarial survival is 49%, and the 4-year is 28.2%. CONCLUSION: Simultaneous chemoradiation is well tolerated with acceptable toxicity. The overall 2- and 4-year actuarial survival is somewhat better than that reported in the literature. Resectability in Stage IIIB patients was not increased with this regimen nor was any surgical specimen free of cancer. The 47% distant failure rate is not different from those reported by others.

Squamous-cell carcinoma of the anus in HIV-positive patients.

PURPOSE: Patients diagnosed as having anal cancer and human immunodeficiency virus (HIV)-positive disease were evaluated for response to treatment and its associated toxicity. METHODS: We studied nine HIV-positive patients with squamous-cell carcinoma of the anus. Among them, three patients had acquired immunodeficiency syndrome (AIDS). The stage of disease at presentation included: one Stage 0, two Stage I, two Stage II, and four Stage III patients. Seven patients received combined modality treatment, i.e., radiation therapy and chemotherapy, and two patients received radiation therapy alone. The radiation therapy field included the pelvis and a conedown boost. Chemotherapy consisted of two cycles of 5-fluorouracil and mitomycin C. Patients have been followed from 2 to 42 (median, 8) months. RESULTS: Seven patients achieved a complete response clinically. All Stage I/II patients and one of four Stage III patients remain alive and have no evidence of disease. Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer Grades 3 and 4 skin toxicity were noted in six patients, and Grades 2 and 3 myelosuppression were noted in eight patients. The response rates achieved are comparable to the experience in non-HIV patients reported in the literature, but toxicity seems to be increased. CONCLUSION: It would seem reasonable to offer combined modality treatment to early stage, HIV-positive patients with good performance status and a history of minor opportunistic infections. The value of combined modality in AIDS patients and those who present with advanced stages of the disease is questionable.

Absorbable mesh in placement of temporary implants.

PURPOSE: To evaluate absorbable mesh for the suturing of afterloading catheters in patients with tumors involving the chest wall. METHODS AND MATERIALS: Patients underwent thoracotomy and resection of tumor; a layer of absorbable mesh was then sutured to the tumor bed. Nylon flexiguide afterloading catheters were sutured into the mesh at about 1.5 cm distance from each other. A second layer of mesh was then sutured on top of the catheters. The chest wall was closed. Orthogonal radiographs and CT scans of the area of implants were done to verify catheter position in each patient on day 1 and on the last day of implant. Computer dosimetry by digitization of dummy sources was performed on each set of radiographs. The same seed for both sets of films was chosen as the origin of digitization. All seed coordinates were compared directly to offset for any rotation of the patient during the two sets of films. The distances were calculated from all seed positions to the origin, then tabulated and compared. RESULTS: The distances agreed within a few millimeters (7-8 mm). The differences may be attributed to the patient's breathing and to the localization uncertainty. The resulting dose alteration was negligible. CONCLUSION: This technique appears to provide adequate anchorage of catheters with resulting constant seed position and dose distribution in areas of scant tissues or in surgical beds of considerable size.

High dose-rate endobronchial irradiation in malignant airway obstruction.

We evaluated the effectiveness of high dose rate (HDR) endobronchial irradiation for palliation of malignant airway obstruction. Between May 1989 and February 1992, 39 patients were treated in our department. Thirty-two patients (82 percent) had primary lung neoplasms and 7 (18 percent) had metastatic disease. Thirty-three patients (85 percent) had prior external irradiation (either alone or in combination with chemotherapy), and 9 patients (23 percent) received laser excision before treatment. Of the 39 patients, 14 (36 percent) presented with hemoptysis, 20 (51 percent) with cough, 15 (38.5 percent) had dyspnea, and 15 patients (38.5 percent) had pneumonia or atelectasis. There were 57 applications performed in the 39 patients. Patients with hemoptysis had 93 percent complete response (CR), 20 percent with cough had CR; 60 percent improved (partial response [PR]); no response was seen in 20 percent. Atelectasis and pneumonia resolved in 20 percent of patients. Eighteen patients (46 percent) underwent a second procedure and were evaluated for objective response; 34 percent had CR, 44 percent had PR, and 22 percent did not respond. There were two acute (one bronchospasm, one pneumothorax) and three late (two strictures, and one exsanguination) complications. In our experience, HDR was highly effective in the palliation of airway symptoms caused by malignant tumors, with acceptable toxicity.

Superior results with complete resection of Askin's tumor.

A malignant small round cell tumor of the thoracopulmonary region arising in childhood has been described by Askin and colleagues. Subsequent descriptions have emphasized refinements (or disagreements) regarding pathology and emphasized the usual poor outcome. Complete excision has not been uniformly attempted in previous series. Our purpose is to describe superior results possible in a multidisciplinary setting emphasizing complete surgical excision.

Choice of procedure for surgical treatment of non-small cell lung cancer.

Asymptomatic coin lesions without specific patterns of benign calcifications can and should have a diagnosis established. Surgical diagnosis can be accomplished with very low morbidity. Accurate staging of lung cancer requires tissue confirmation of mediastinal node status either by thorough sampling or by complete node dissection. Complete resection with lobectomy is the preferred treatment providing better results than lesser resections. Segmental or wedge resections and internal radiotherapy are appropriate for patients unable to tolerate lobectomy. Video assisted thoracoscopy may prove useful in wedge excision for patients with poor pulmonary reserve.

Simultaneous chemoradiation in advanced non-small cell lung cancer.

We designed our study to evaluate the safety and efficacy of simultaneous chemoradiation therapy in an accelerated, twice-a-day schedule to improve local control and survival in advanced lung cancer patients. Forty-one patients were entered into the study. Twenty-three had stage IIIB and 18 had stage IIIA disease. They received cisplatin 30 mg/m2, VP-16 80 mg/m2, and 5-Fluorouracil (5-FU) 900 mg/m2 in iv infusion. Radiation therapy consisted of 2G twice a day for 5 days, followed by a 2-week rest. This cycle was repeated 3 times. Patients were evaluated for surgical resection after the second cycle. Acute toxicity was acceptable: 3 patients expired (1 congestive heart failure, 1 sepsis, 1 pulmonary embolism). The 1-year actuarial survival was 60.3%; the 2-year actuarial survival was 55.3%. Our results show that this regimen is well tolerated and that the 2-year actuarial survival appears to be comparable to that reported in the literature.

Chemotherapy rapidly alternating with accelerated radiotherapy for advanced carcinomas of the hypopharynx and upper esophagus: a feasibility study.

Patients with advanced carcinomas of the hypopharynx or upper esophagus have among the worst prognoses in head and neck oncology. We developed a treatment regimen of rapidly alternating multi-agent chemotherapy and accelerated interrupted radiotherapy as follows: Three cycles of chemotherapy were delivered [day 1, cisplatin 100 mg/m2; days 1-4, 5-fluorouracil (5-Fu) 900 mg/m2] and repeated every 3 weeks. On day 8 of each chemotherapy cycle radiotherapy was started, consisting of 10 fractions of 200 cGy delivered twice daily, for 5 days. The total dose of radiotherapy was 6,000 cGy over 7 weeks, and the total duration of chemotherapy and radiotherapy was 8 weeks. Nineteen patients with locally advanced, epidermoid carcinoma of the hypopharynx (9 patients) or upper esophagus (10 patients) were treated on this protocol. Minimum follow-up was 1 year. Twelve patients had tumors judged technically unresectable, whereas 7 had tumors considered resectable only with total laryngectomy, which was unacceptable to the patients. One patient died of nadir sepsis during treatment, but otherwise the acute toxicity was relatively mild (grade I/II in 16 patients, grade III/IV in 3 patients). The complete response rate was 83% (15 of 18 patients), and the partial response rate was 17% (3 of 18). No patient failed to respond. The survival rate was 80% at 1 year and 73% at 18 months. At 1 year, 89% of the patients remained in remission and at 18 months, 74% Late complications occurred in 4 patients. These included laryngeal necrosis, pneumonitis, esophageal stricture, and tracheoesophageal fistula.(ABSTRACT TRUNCATED AT 250 WORDS)