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Second solid tumors in patients with Hodgkin's disease cured after radiation or chemotherapy plus adjuvant low-dose radiation.

PURPOSE: Late solid tumors (STs) are a significant cause of morbidity and mortality in long-term survivors of Hodgkin's disease. To investigate the carcinogenic potential of two different therapeutic approaches, we measured the relative risk (RR) of STs in patients with early-stage disease cured after primary full-dose (approximately 40 Gy) radiation therapy (RT) and in patients with advanced disease who were treated with chemotherapy followed by low-dose (15 to 30 Gy) involved-field radiation (CMT). PATIENTS AND METHODS: Because therapy-induced STs generally begin after a latency period of 5 to 10 years, we restricted our analysis to patients treated before 1986 who achieved durable remissions. Patients who required salvage chemotherapy or who died of Hodgkin's disease were excluded from analysis. The RR of STs was calculated by dividing the observed number of cases by the expected number in a matched population from the Connecticut Tumor Registry. The actuarial incidence of STs was also measured. RESULTS: A total of 197 patients formed the RT group and 116 the CMT group. The median follow-up period in the RT group was 12.8 years, versus 13.5 years in the CMT group. The overall RR of STs in the CMT group was 1.5 (95% confidence interval [CI], 0.6 to 3.5; P = .122). There were no cases of lung or breast cancer. In the RT group, the overall RR of STs was 3.3 (95% CI, 2.0 to 5.3; P < .001). There were seven cases of lung cancer (RR = 10.8; 95% CI, 5.3 to 22.2; P < .001) and two cases of breast cancer (RR = 2; 95% CI, 0.6 to 7.4; P = .07). All six benign tumors occurred in the RT group. CONCLUSION: In patients cured by initial treatment for Hodgkin's disease, RT was associated with a statistically significant increase in STs, particularly lung cancer. CMT was not associated with a significant increase in STs. These data may have important implications for the design of newer therapies for early-stage Hodgkin's disease.

Actuarial Analysis↗

Phase II study of neoadjuvant chemotherapy and radiation therapy in the management of high-risk, high-grade, soft tissue sarcomas of the extremities and body wall: Radiation Therapy Oncology Group Trial 9514.

PURPOSE: On the basis of a positive reported single-institution pilot study, the Radiation Therapy Oncology Group initiated phase II trial 9514 to evaluate its neoadjuvant regimen in a multi-institutional Intergroup setting. PATIENTS AND METHODS: Eligibility included a high-grade soft tissue sarcoma > or = 8 cm in diameter of the extremities and body wall. Patients received three cycles of neoadjuvant chemotherapy (CT; modified mesna, doxorubicin, ifosfamide, and dacarbazine [MAID]), interdigitated preoperative radiation therapy (RT; 44 Gy administered in split courses), and three cycles of postoperative CT (modified MAID). RESULTS: Sixty-six patients were enrolled, of whom 64 were analyzed. Seventy-nine percent of patients completed their preoperative CT and 59% completed all planned CT. Three patients (5%) experienced fatal grade 5 toxicities (myelodysplasias, two patients; infection, one patient). Another 53 patients (83%) experienced grade 4 toxicities; 78% experienced grade 4 hematologic toxicity and 19% experienced grade 4 nonhematologic toxicity. Sixty-one patients underwent surgery. Fifty-eight of these were R0 resections, of which five were amputations. There were three R1 resections. The estimated 3-year rate for local-regional failure is 17.6% if amputation is considered a failure and 10.1% if not. Estimated 3-year rates for disease-free, distant-disease-free, and overall survival are 56.6%, 64.5%, and 75.1%, respectively. CONCLUSION: This combined-modality treatment can be delivered successfully in a multi-institutional setting. Efficacy results are consistent with previous single-institution results.

Adult↗

Comparison of forward planned conformal radiation therapy and inverse planned intensity modulated radiation therapy for esthesioneuroblastoma.

The purpose of this study was to compare dose distribution of inverse planned intensity modulated radiation therapy (IMRT) with that of conformal radiation therapy (SCRT) in the treatment of esthesioneuroblastoma, and to report initial clinical results. 13 patients with esthesioneuroblastoma were planned both with IMRT and SCRT using complete three-dimensional data sets. A target dose of 60 Gy was prescribed. We performed a detailed dose volume histogram analysis. Dose coverage was equal in both plans while dose distribution was more conformal to the target volume with IMRT. Mean and maximum dose of the brain stem, chiasm, optic nerves and orbits were lower using IMRT than SCRT. The reduction was significant regarding orbit and optic nerve (p<0.05). IMRT was superior in sparing of organs at risk compared with SCRT. The additional sparing by IMRT was positively correlated to the size of the target volume, which was evident with target volumes above 200 cm3. Treatment time was approximately 20 minutes per fraction using IMRT compared with 15 minutes per fraction using SCRT. We conclude that IMRT is both feasible and a valuable tool for more conformal dose distribution in the treatment of esthesioneuroblastoma and to spare organs at risk that are in critical relationship to the tumour. This advantage could be seen especially well in complex shaped target volumes above 200 cm3. Thus, using IMRT, risk of complications may be minimized and local tumour control may be increased.

Esthesioneuroblastoma, Olfactory↗

The effect of ionizing radiation on epidermal Langerhans cells--a quantitative analysis of autopsy cases with radiation therapy.

Langerhans cells (LCs) are dendritic cells located in the epiderm is with antigen-presenting capacities. We performed a quantitative analysis of LC density in the anterior chest skin of 286 autopsy cases, including 31 cases treated with radiation therapy. Skin specimens were stained by immunoperoxidase technique (PAP method) with an anti-S-100 protein antiserum. S-100 positive LCs were counted for comparison between non-irradiated and irradiated cases. In this study we noted that, 1) The decline in density of the LCs was age-related and dendritic processes were more prominent in younger groups. 2) The cases irradiated within one month before autopsy showed a reduction in LC density compared with age-matched controls. 3) The cases irradiated more than one month before autopsy demonstrated no consistent or definite tendency. It is suggested that ionizing irradiation as well as ultraviolet light may deplete the LC density in an acute phase. The possibility that radiation therapy alters immunological surveillance in the human skin is discussed.

Adolescent↗

Radiation-chemical discussion on inverse dose-rate effect observed in radiation-induced strand breaks of plasmid DNA.

Experimental results of inverse dose-rate effect, so-called Kada Effects, which was published by Takakura and her coworkers on radiation-induced strand breaks of plasmid DNA in aerated aqueous solution, have been kinetically analyzed and discussed on the basis of radiation chemistry, the kinetic analysis indicates that there are two possible mechanisms; 1) equilibrium mixture of O2- and HO2 is responsible for strand breaks of DNA, and 2) peroxyl radical produced from citrate is effective for the strand breaks. However, the detailed kinetic analysis revealed that the latter is improbable because unimolecular decay of the peroxyl radical must be assumed to be negligible for its participation despite fast decay of analogous organic peroxyl radicals. The analysis has also given 9.93 +/- 0.10 dm3 mol-1 s-1 per nucleotide unit, which corresponds to 7.62 x 10(4) dm3 mol-1 s-1 per DNA molecule, as the rate constant for the reaction of the equilibrium mixture with plasmid pBR 322 DNA. Furthermore the probability that the reaction of the mixture with a nucleotide unit of DNA leads to strand breaks was obtained to be 3.36 x 10(-3) for gamma-irradiated system and 1.98 x 10(-3) for beta-irradiated system, respectively.

DNA↗

Dosimetry for quantitative analysis of the effects of low-dose ionizing radiation in radiation therapy patients.

We have developed and validated a practical approach to identifying the location on the skin surface that will receive a prespecified biopsy dose (ranging down to 1 cGy) in support of in vivo biological dosimetry in humans. This represents a significant technical challenge since the sites lie on the patient's surface outside the radiation fields. The PEREGRINE Monte Carlo simulation system was used to model radiation dose delivery, and TLDs were used for validation on phantoms and for confirmation during patient treatment. In the developmental studies, the Monte Carlo simulations consistently underestimated the dose at the biopsy site by approximately 15% (of the local dose) for a realistic treatment configuration, most likely due to lack of detail in the simulation of the linear accelerator outside the main beam line. Using a single, thickness-independent correction factor for the clinical calculations, the average of 36 measurements for the predicted 1-cGy point was 0.985 cGy (standard deviation: 0.110 cGy) despite patient breathing motion and other real-world challenges. Since the 10-cGy point is situated in the region of high-dose gradient at the edge of the field, patient motion had a greater effect, and the six measured points averaged 5.90 cGy (standard deviation: 1.01 cGy), a difference that is equivalent to approximately a 6-mm shift on the patient's surface.

Biopsy↗

Radiation-induced diffuse brain injury in the neonatal rat model--radiation-induced apoptosis of oligodendrocytes.

The mechanism of radiation-induced diffuse brain injury was investigated using a model of delayed myelination in the irradiated neonatal rat brain in which the number of oligodendrocytes decreases without associated necrosis of the cerebral white matter. Immunohistochemical analysis using antibody against the large myelin-associated glycoprotein, a specific marker of oligodendrocytes at an early stage of development, showed that the number of the oligodendrocytes associated with myelination decreased in the irradiated hemisphere 1 day after irradiation and remained low until 5 days after irradiation. In situ terminal deoxynucleotidyl transferase-mediated nick end-labeling assay revealed that apoptosis mainly occurred in the cerebral white matter of the irradiated hemisphere. Three hours after irradiation, apoptotic cells were found in the subcortical white matter and the periventricular white matter. Six hours after irradiation, apoptotic cells were found in the internal capsule, and the numbers of apoptotic cells in the periventricular white matter and subcortical white matter increased. One day after irradiation, the number of apoptotic cells in the periventricular white matter decreased. Three days after irradiation, apoptotic cells were not observed in the cerebral white matter. These results suggest that the oligodendrocytes associated with myelination may be damaged via radiation-induced apoptosis, and depletion of the oligodendrocytes may cause delay of myelination.

Animals↗

Radiation injury to the liver after intensity-modulated radiation therapy in patients with mesothelioma: an unusual CT appearance.

OBJECTIVE: We sought to report the unusual distribution of radiation-induced injury to the liver in patients with mesothelioma after extrapleural pneumonectomy and intensity-modulated radiation therapy (IMRT). CONCLUSION: Abnormal hepatic enhancement after extrapleural pneumonectomy and IMRT is common in patients with mesothelioma. Knowledge of the early occurrence and typical location and appearance of IMRT-induced injury can be useful in preventing misinterpretation as metastatic disease or recurrent tumor.

Aged↗

Excerpts from Maintaining Radiation Protection Records. National Council on Radiation Protection and Measurements.

This is the first of a three-part series of articles from a report by the NCRP, to be reprinted in successive issues of Radiology Management. The report offers practical recommendations for establishing a radiation safety program. Different aspects of record-keeping, an essential part of all radiation safety programs, will be highlighted in each article. The introduction and a chapter on the systematic generation of records are included in this issue.

Facility Regulation and Control↗

Comparative analysis of proinflammatory cytokines in plasma of mice exposed to radiation or in combined radiation injury.

Male mice (CBA x C57BL/6)F1 were used for the experiments throughout this study. Blood serum levels of IL-1 beta, IL-6, TNF-alpha, IL-3, and GM-CSF were evaluated by means of enzyme-linked immunosorbent assay at 3, 6, 24, 48 and 72 hours after 7 Gy gamma-irradiation alone or combined injury (irradiation + thermal burn). Radiation as well as combined injury did not cause any important alterations of IL-1 beta, TNF-alpha, IL-3, and GM-CSF concentrations in the system circulation. Combined injury revealed more enhanced serum levels of IL-6 versus only irradiated mice. A possible significance of this phenomenon at the combined radiation and thermal burns' pathogenesis is discussed.

Animals↗

[A case of radiation lung injury with characteristics of bronchiolitis obliterans organizing pneumonia after radiation therapy for breast carcinoma].

We report a case of sputum and dyspnea with patchy migratory air space infiltrates that developed in a 49-year old woman after she started breast radiation therapy following surgery for breast carcinoma. Our case clearly differed from ordinary radiation pneumonitis. Chest roentogenography and computed tomographic (CT) scanning demonstrated alveolar opacities. Bronchoalveolar lavage showed a moderate elevation of the total cell concentration and a considerable increase of lymphocytes, and transbronchial lung biopsies revealed a histological pattern of bronchiolitis obliterans organizing pneumonia with intra-alveolar granulation tissue. The present case suggests that breast irradiation may contribute to the development of a histological pattern of bronchiolitis obliterans organizing pneumonia.

Breast Neoplasms↗

[A possibility to predict the severity of individual damage following the exposure to supralethal radiation dosage. Prediction of the clinical manifestation of radiation injury in laboratory animals by response to pre-exposure hypobaric hypoxia].

The experiments on rats, dogs and monkeys exposed to radiation doses which cause intestinal and cerebral forms of radiation sickness have shown that the severity of a clinical state can be predicted by cardiovascular and endocrine changes when a pre-exposure test with moderate hypobaric hypoxia is performed. The goodness of fit of experimental data to the exposed result is up to 60-80%, still rising if a set of indices of the neuroendocrine status is used.

Animals↗

[Evaluation of radiation dose and radiation risk for dental patients].

1. The collective dental radiation dose in Israel in 1998 is 42.86 Sv. 2. The collective dental radiation is responsible for a mortality of about 2.14 people per year in Israel, and a similar number of morbidity from non-lethal cancer. 3. It seems that the quality of the picture in dental radiographs in Israel is not satisfactory, so is the dentists' level of knowledge about it. 4. Exposure to dental radiographs may be reduced by half if measures are taken to ensure the quality of the radiographs and the knowledge of dentists on the subject.

Clinical Competence↗

[Radiation-induced apoptosis in vivo: therapeutic significance of apoptosis in radiation therapy].

Apoptotic cell death is frequently found in certain tumor cells after irradiation; however, the incidence is not always high in vivo. Seven tumors were transplanted to nude mice, and their organs were histologically examined after irradiation to study the therapeutic significance of apoptosis in radiation therapy. A high incidence of apoptosis was found only in radiosensitive tumors or normal cells with wild-type p53, but the peak incidence in most cells was only a few percent or less. However, the calculated total incidence of apoptotic cell death was much higher than the actual peak incidence, because the half-life of apoptosis is very short. Even in radioresistant tumors, total radiation-induced apoptosis was estimated to be about 10 percent. These results suggest that apoptotic cell death in radiotherapy may be more important in vivo than previously estimated.

Animals↗

Radiation synovectomy of the ankle with 75 MBq colloidal 186rhenium-sulfide: effect, leakage, and radiation considerations.

OBJECTIVE: In a retrospective study we evaluated the effect, duration of effect, and safety of radiosynoviorthesis of the ankle in patients with persistent synovitis, refractory to disease modifying antirheumatic drugs (DMARD) and intraarticular glucocorticoid injections. We estimated leakage and dose to target and non-target organs. METHODS: Radiation synovectomy was performed by injection of 75 MBq 186rhenium colloid and 20 mg triamcinolone-hexacetonide mixed in a volume of about 1.5 ml. About 24 hours after injection, leakage of the radionuclide was measured with a single-head gamma camera, with views of the ankle joint, regional (inguinal) lymph nodes, and liver. Leakage was expressed as counts in the target region of interest corrected for background relative to total counts corresponding with percentage of injected dose. The effect of radiosynoviorthesis was scored into 3 categories: (1) No effect, i.e., persistent synovitis or only minimal reduction of swelling and/or pain, or the need of intraarticular glucocorticoid injection within 3 months or arthrodesis of the treated joint within 6 months. (2) Moderate effect, i.e., significant reduction of swelling, pain, and improvement of function. (3) Good effect, i.e., complete or almost complete remission of synovitis. RESULTS: The mean age of patients (28 women, 12 men) at the time of treatment was 58 years (range 33-76); 54 consecutive procedures in ankles of the 40 patients were evaluated. No effect was found in 12 of 54 (22%) treated joints; moderate effect in 12 (22%), with a mean duration of effect of 34 months (range 12-49); and good effect in 30 (56%), with a mean duration of effect of 41 months (range 21-75). Mean effect-duration did not differ significantly between the moderate and good effect groups. Mean leakage did not differ significantly between the effect groups. CONCLUSION: Radiation synovectomy of the ankle is a safe and effective treatment in persistent synovitis, although all patients eventually experienced recurrence of arthritis.

Adult↗

Practical aspects of inverse-planned intensity-modulated radiation therapy for prostate cancer: a radiation treatment planner's perspective.

INTRODUCTION: From a radiation treatment planner perspective, in the treatment of prostate cancer, inverse-planned intensity-modulated radiation therapy (IMRT) differs considerably from conventional, conformal, and forward-planned IMRT. In this work we aim to discuss the rationale behind the use of inverse-planned IMRT for the treatment of prostate cancer, as well as some of the practical aspects, including the differences in planning strategies, dose fractionation and issues in plan evaluation. DISCUSSION: The primary motivation behind the use of inverse-planned IMRT for prostate cancer radiotherapy is to attempt further dose escalation while maintaining critical structure and healthy tissue sparing at an acceptable level. The sparing of normal tissues is largely dependent on the size of the planning target volume (PTV) defined, and if the PTV overlaps critical structures. Depending on how the PTV is defined it may be impossible to achieve the desired healthy tissue sparing even with IMRT. A second role for the use of IMRT in the treatment of prostate cancer may be to conform the isodose distribution to a complex PTV, such as one that includes the seminal vesicles or the pelvic lymph nodes in the treatment volume. Finally, inverse planned IMRT may be useful in the planning and delivery of simultaneous integrated boosts where different parts of the target structures receive different daily doses. This again has applications for the simultaneous treatment of pelvic lymph nodes with the prostate treatment volume, and presents interesting opportunities for hypo-fractionation. All of these options of course require careful plan evaluation with respect to isodose distributions and dose-volume constraints as well as the radiobiological consequences of using unconventional fractionation. CONCLUSION: IMRT seems to be the most effective modality for treating complex target geometries and for delivering simultaneous integrated boosts. In particular for prostate cancer, the simultaneous treatment of the prostate and pelvic lymph nodes lends itself perfectly to IMRT, allowing the prostate to receive a higher daily dose per fraction, as well as minimizing the amount of small bowel in the field, while at the same time sparing the rectum and bladder adequately. Inverse-planned IMRT is, however, a complex procedure, and to safely implement it, an extensive patient- and machine-specific quality assurance program is required.

Dose-Response Relationship, Radiation↗