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PubMed2002

Twelve versus six months of clopidogrel to reduce major cardiac events in patients undergoing gamma-radiation therapy for in-stent restenosis: Washington Radiation for In-Stent restenosis Trial (WRIST) 12 versus WRIST PLUS.

BACKGROUND: Intracoronary gamma-radiation reduces recurrent in-stent restenosis (ISR). Late thrombosis was attenuated with 6 months of aspirin and clopidogrel. We aimed to find out whether 12 months of aspirin plus clopidogrel is superior to a strategy of 6 months after radiation therapy for patients with ISR. METHODS AND RESULTS: One hundred twenty consecutive patients with diffuse ISR in native coronaries and vein grafts with lesions <80 mm in length underwent PTCA, laser ablation, or rotational atherectomy. Additional stents were placed in 39 patients (33%). After the intervention, a ribbon with different trains of radioactive 192Ir seeds was positioned to cover the treated site, and a dose of 14 Gy to 2 mm was prescribed. Patients were discharged with clopidogrel and aspirin for 12 months and followed up clinically. The cardiac clinical event rates at 15 months were compared with the gamma-treated (n=120) patients of the WRIST PLUS study (only 6 months of antiplatelet therapy). Whereas the late thrombosis rates were similar (3.3% for the group given 12 months of antiplatelet therapy versus 4.2% for the group given 6 months, P=0.72), the group treated with 12 months of antiplatelet therapy had a rate of 21% for major adverse cardiac events and 20% for target-lesion revascularization compared with 36% (P=0.01) and 35% (P=0.009), respectively, in patients who were treated with only 6 months of clopidogrel. CONCLUSIONS: Twelve months of clopidogrel is superior to 6 months in reducing overall major cardiac events and revascularization rates at 15 months for patients with ISR treated with gamma-radiation. At least 12 months of clopidogrel therapy should be recommended for patients undergoing radiation therapy for ISR.

Aspirin↗

PubMed2005

Long-term survival rates of laryngeal cancer patients treated by radiation and surgery, radiation alone, and surgery alone: studied by lognormal and Kaplan-Meier survival methods.

BACKGROUND: Validation of the use of the lognormal model for predicting long-term survival rates using short-term follow-up data. METHODS: 907 cases of laryngeal cancer were treated from 1973-1977 by radiation and surgery (248), radiation alone (345), and surgery alone (314), in registries of Connecticut and Metropolitan Detroit of the SEER database, with known survival status up to 1999. Phase 1 of this study used the minimum chi-square test to assess the goodness of fit of the survival times of those who died with disease to a lognormal distribution. Phase 2 used the maximum likelihood method to estimate long-term survival rates using short-term follow-up data. In order to validate the lognormal model, the estimated long-term cancer-specific survival rates (CSSR) were compared with the values calculated by the Kaplan-Meier (KM) method using long-term data. RESULTS: The 25-year CSSR were predicted to be 72%, 68% and 65% for treatments by radiation and surgery, by radiation alone, and by surgery alone respectively, using short-term follow-up data by the lognormal model. Corresponding results calculated by the KM method were: 72+/-3%, 68+/-3% and 66+/-4% respectively. CONCLUSIONS: The lognormal model was validated for the prediction of the long-term survival rates of laryngeal cancer patients treated by these different methods. The lognormal model may become a useful tool in research on outcomes.

Adult↗

PubMed2002

Angiotensin II blockade reduces radiation-induced proliferation in experimental radiation nephropathy.

Total-body irradiation or renal irradiation is followed by a well-defined sequence of changes in renal function leading eventually to renal failure. Previous studies in a rat model have shown that inhibition of angiotensin-converting enzyme or blockade of angiotensin II receptors can prevent the structural and functional changes that occur after renal irradiation, and that these interventions are particularly important between 3 and 10 weeks after irradiation. We have now shown that in the same rat model, total-body irradiation induces proliferation of renal tubular cells (i.e., an increase in the number of cells staining positive for proliferating cell nuclear antigen) within 5 weeks after irradiation. Treatment with an angiotensin II receptor blocker delays this radiation-induced tubular proliferation and decreases its magnitude. Renal radiation also induces proliferation of glomerular cells, but the relative increase in glomerular proliferation is not as great as that seen in renal tubular cells, and the increase is not delayed or decreased by treatment with an angiotensin II receptor blocker. We hypothesize that angiotensin II receptor blockers exert their beneficial effect in radiation nephropathy by delaying the proliferation (and hence the eventual mitotic death) of renal tubular cells that have been genetically crippled by radiation.

Angiotensin Receptor Antagonists↗

PubMedDate not supplied

The effect of surgery, radiation therapy, and combined radiation therapy and chemotherapy on immunocompetence in patients with lung carcinoma.

The immunologic status of 59 patients with lung carcinoma was determined by analysis of peripheral venous blood samples. The following tests were performed: total leucocyte and lymphocyte counts, the number of acid alpha-naphthyl acetate esterase (ANAE) positive cells (T-cells), and phytohaemagglutinin (PHA) and tuberculin (PPD) transformation tests. The patients were divided into three treatment groups: a surgery group (S), a radiation therapy group (R), and a combined cytostatic and radiation therapy group (C). A follow-up was carried out 4 to 6 months after treatment. The therapeutic measures, resection, irradiation, and chemotherapy, produced a decrease in the total leucocyte and lymphocyte counts, in the number of T-cells, and in the leucocyte transformation response to PPD. In the surgically treated group the decrease was transient. In the groups treated with radiation therapy and combined cytostatic and radiation therapy the values remained low throughout the follow-up. The lymphocyte response to PHA was not altered in any of the groups during initial treatment or follow-up. The results did not suggest a correlation between the immunologic parameters used and the stage and histologic type of lung cancer. The tests were of no clinical value in the determination of the individual prognosis.

Adult↗

PubMed2002

[Current status of radiation therapy--evidence-based medicine (EBM) of radiation therapy. Current management of patients with esophageal cancer].

The best management for small mucosal esophageal cancer is generally endoscopic mucosal resection. However, for submucosal cancer and extensive mucosal cancer, either radical surgery or radiation seems to be an equally efficacious option. Radiation therapy concurrent with chemotherapy is more effective than radiation therapy alone for patients with unresectable esophageal cancer. The key drugs are cisplatin and 5-fluorouracil. However, for patients with poor performance status or for aged patients, radiation therapy alone is still a choice of treatment. Surgery has generally been indicated for patients with resectable esophageal cancer. However, outcomes of concurrent chemoradiation therapy may be comparable with those of surgery. Therefore, a prospective randomized study should be performed to determine the best management for patients with resectable esophageal cancer. The usefulness of intra-cavitary irradiation for esophageal cancer has not been clarified. A prospective randomized trial with a large number of patients is necessary to determine the effectiveness of intra-cavitary irradiation. The best management for patients with loco-regionally recurrent esophageal cancer after surgery has not been determined. Intensive therapy should be considered if the site of recurrence is limited and the time interval from surgery to recurrence is long. Chemotherapy is essential in the management of patients with small cell esophageal cancer. However, the best local therapy has not been determined.

Combined Modality Therapy↗

PubMed2002

Radiation therapy after radical prostatectomy: why patience is a virtue! The case for salvage radiation therapy.

Without reliable clinical or pathologic predictors of local recurrence, selection of patients for adjuvant radiotherapy based on any combination of clinical or pathological parameters is bound to lead to the unnecessary treatment of significant numbers of patients whose disease might not have ultimately recurred or who might have been destined to have recurrence with extrapelvic metastatic disease, for which pelvic radiation would be ineffective. Furthermore, new ultrasensitive prostate-specific antigen (PSA) assays can identify patients actually failing surgery with a detectable and rising PSA earlier than ever, when disease volume is low and still amenable to salvage radiation therapy, and can allow the calculation of the PSA doubling time, which is gaining widespread acceptance as a proven predictor of response to salvage radiation therapy in this setting. Therefore, the rationale for preemptive adjuvant radiation therapy after radical prostatectomy is weaker than ever.

Journal Article↗

PubMed1989

Derivation of radiation quality average parameters in neutron-gamma radiation fields with the high-pressure ionization chamber: theory and practice.

The established radiation quality parameters in mixed neutron-gamma radiation fields may be measured by applying the initial (columnar) recombination of ions in tissue-equivalent (TE) high-pressure ionization chambers (recombination chambers). The mean quality factor can be determined to within 10-15% for mixed fields with neutrons ranging from thermal to 10 MeV, and the dose mean LET of the proton component can be determined to within 10-15% if the gamma-ray absorbed dose fraction is known. These average parameters are derived by measuring the ratio of the ionization currents collected at two high-field strengths and constant gas pressure applied to the ionization chamber. By utilizing approximate correlations between physical parameters in the neutron energy region from thermal to 10 MeV, the dose mean LET of the heavy ion component, the overall dose mean LET, and the microdosimetric parameter y0,D of the mixed field can also be derived. Experimental verification of the method is presented for various neutron-gamma radiation spectra in air and in water by comparison to theoretical calculations and results from low-pressure proportional counter measurements. Good agreement is shown. The TE high-pressure ionization chamber appears to have wide potential for use as a dose-equivalent meter in radiation protection or as a beam characterization device in radiobiology.

Energy Transfer↗

PubMed1988

Effect of ionizing radiation on thymic epithelial cell function. I. Radiation-spared thymic epithelial grafts expedite the recovery of T cell function in lethally irradiated and fetal liver reconstituted mice.

A murine model system was developed to determine whether ionizing radiation has a detrimental influence on thymic epithelium, cell function. Normal mice were lethally irradiated, grafted intracamerally with normal fetal thymic epithelium, and then reconstituted with fetal liver cells. These animals were compared with a group of animals who received their thymic grafts before the irradiation protocol. Analysis of the reconstitution of T cell function in peripheral lymph nodes and spleens at various times post transplantation demonstrated that animals with radiation-spared thymic grafts had superior proliferative responses to T cell mitogens and alloantigens. It was also determined that the capacity of these animals to elicit contact hypersensitivity responses was significantly greater when compared with animals whose thymic grafts had been radiated. The observed difference in T cell function could not be ascribed to a difference in the rate of export of mature T cells from the thymic grafts since the absolute number of Thy-1+, L3T4+, or Lyt-2+ lymphocytes present in the peripheral lymphoid compartment of our two groups of animals was equivalent. Immunohistologic analysis of the thymic grafts demonstrated a marked reduction in the medullary compartment of the repopulated grafts that had been exposed to ionizing radiation. The results of this study suggest: 1) that irradiation of the thymic microenvironment during marrow ablative preparative regimens may be in part responsible for some of the immune alterations observed in marrow transplant recipients, and 2) that our model system may provide a valuable tool for delineating the roles played by medullary and cortical epithelial cells of the thymus on the T cell maturation and education processes.

Animals↗

PubMed1986

The treatment of single brain metastasis from non-oat cell lung carcinoma. Surgery and radiation versus radiation therapy alone.

Between 1978-1980, 104 patients with single brain metastases (SBM) from non-small cell lung carcinoma (NSCLC) were treated at Memorial Sloan-Kettering Cancer Center (MSKCC). These included 35 patients treated with surgical resection and radiation (S + ERT) and 69 patients treated with conventional external beam radiation therapy alone (ERT). Surgical resection was combined with whole brain (WBRT) and focal radiation in 83% and 17% of patients, respectively. In the ERT group, all patients received WBRT. Both treatment groups were similar with regard to age, sex, stage distribution, location and size of SBM, and time to relapse from initial diagnosis of NSCLC. The histologic examination, however, revealed adenocarcinoma predominating in those patients receiving S + ERT and epidermoid carcinoma in those receiving ERT. Follow-up treatment, symptomatic, and CTT response rates were evaluated. With S + ERT, the overall subjective and objective responses were 80% and 87%, respectively, and with ERT, 83% and 72% (of the 47 patients available for follow-up CT scans), respectively. Survival data indicate a significant advantage of S + ERT over ERT with a median survival of 16 months versus 4 months (P less than 0.0001). Three major factors, however, may have contributed to this difference: (1) patients in the S + ERT group generally received more aggressive initial treatment to the primary disease in the lung (72%) compared to the ERT group (36%); (2) in the S + ERT group, extracranial disease was absent at the time of SBM diagnosis in 49% of the S + ERT group compared to 26% in the ERT group; and (3) distant metastases were present in only 6% of the surgical patients yet, they were present in 49% of those treated with radiation alone. In one subset of patients, however--those with a radically treated primary and no extracranial disease--S + ERT resulted in a median survival of 33 months with 33% of the population still alive with no evidence of disease compared to 12 months and 0%, respectively, with ERT alone. Moreover, intracranial relapse was the cause of death in only one S + ERT patient (9%), yet it accounted for 50% of the ERT deaths. These data suggest that an aggressive approach to SBM in such favorable prognostic patients may indeed improve survival.

Adenocarcinoma↗

PubMed1984

[Effect of sensitizing doses of radiation on hormonal homeostasis in combined radiation treatment of cervical cancer].

Low sensitizing doses given to patients with cervical carcinoma in the course of complex radiation treatment were responsible for a greater decrease in the frequency of radiation injuries to the intestine as compared with standard complex radiation procedure. This was matched by an increase in the incidence of exacerbation of chronic adnexitis. Radiation appeared to inhibit thyroid function. Low sensitizing dose treatment given in the course of complex radiotherapy did not affect the gland's function. However, cases of stage III cancer exhibited a more pronounced decrease in thyrotrophin levels accompanied by higher somatotropin levels.

Brachytherapy↗

PubMed1993

[Radiation stenosis and fistula formation developed after iridium-192 high-dose-rate intracavitary radiation boost therapy for carcinoma of the esophagus].

Intracavitary irradiation using a high-dose-rate Ir-192 remote after-loading system was applied to 14 advanced or inoperable patients with esophageal carcinoma as a boost therapy. The total dose of external irradiation was 45-70 Gy/15-35 fractions and that of intracavitary irradiation was 11.6-34.0 Gy/2-4 fractions at a point 5 mm deep from the inner surface of the esophageal mucosa. The time-dose-fractionation factor (TDF) of the whole treatment was 116-186 (mean, 146). Six patients (43%) had complete response (CR), three (21%) had partial response and five (36%) had no response. Esophageal carcinoma that showed exophytic growth, was less than 5 cm ling, and showed favorable response to external irradiation was likely to be a good candidate for intracavitary radiation boost therapy. Fistula formation was produced in five patients (36%), four of whom were irradiated at more than 140 TDF. All six CR patients were free from esophageal tumors, but severe esophageal stenosis due to radiation injury developed in five (83%) of them. They were irradiated at more than 135 TDF. One- and two-year survival rates were 28.6% and 14.3%, respectively. The poor prognosis was ascribed to the frequent occurrence of fatal radiation stenosis and fistula formation. An appropriate therapeutic dose for esophageal carcinoma that does not cause severe radiation stenosis was estimated to be under 120 TDF.

Aged↗

PubMed1977

Results of radiation therapy and a combination of radiation and surgery in the laryngeal cancer.

A total of 348 out of 349 patients with laryngeal cancer were treated over the period 1960-1970. Radiation therapy alone was used in 262 of them and surgical intervention with postoperative irradiation in 86. Results in the form of a five-year survival rate in the group treated solely by irradiation were superior by 12% in the case of glottic than in that of supraglottic carcinoma (48.8% and 36.8% respectively). In the group of patients operated upon and subsequently irradiated, relatively satisfactory results were obtained in the advanced, i. e. the III stage of supraglottic carcinoma (5-year survival in 61.4%). The overall 5-year survival rate in the patients operated upon and then irradiated proved to be better by 24.5% in supraglottic and by 4.1% in the glottic carcinoma, than in patients subjected solely to irradiation. Of 27 cases of relapses, 6 patients were successfully treated by laryngectomy. Post-irradiation complications involved most frequently minor cases of endolaryngeal edema; among the more serious ones were 2 cases of radiation myelitis. The discussion on the problem of radiation dosage in cancer of the larynx, the treatment of regional metastases and combined surgico-radiation therapy.

Aged↗

PubMed1992

Radiation-induced lymphoid tumors and radiation lethality are inhibited by combined treatment with small doses of zinc aspartate and WR 2721.

Combined small doses of zinc aspartate and WR 2721 provided additive protection against radiation lethality in mice. Survival obtained with a small dose of WR 2721 which was ineffective alone could be enhanced to 83% by combining the drug with zinc aspartate, which on its own also displayed no effect. The survival of 25% provided by a higher dose of WR 2721 was increased significantly by adding zinc aspartate. Additivity was also tested in a model of radiation carcinogenesis. For this purpose, lethality and occurrence of lymphoid tumors induced by fractionated total-body irradiation were studied in C57B1/6 mice treated with zinc aspartate and WR 2721. In order to reveal additive effects, both agents were used at sub-optimal dosages. In mice subjected to 5 daily exposures of 1.9 Gy, the combination of zinc aspartate and WR 2721 was effective and enhanced the survival to 83% as compared with 25% afforded by WR 2721 alone (p < 0.005). Similarly, histological assessment of organ involvement with lymphoma revealed that zinc aspartate and WR 2721 alone did not bring about a significant reduction of lymphoma incidence. On the other hand, the combined agents diminished organ involvement with lymphoma to 9.1% as against 90% in the controls (p < 0.0005) and 62.5% with WR 2721 alone (p < 0.025). Thus, combined treatment with zinc aspartate and WR 2721 also inhibited radiation-induced lymphoid tumors.

Amifostine↗

PubMed1979

The relation of radiation sensitivity to pronuclear chromosome structure. II. Differences in radiation sensitivty between two stocks of Phryne cincta characterized by low or high crossing-over frequency.

After treatment of spermatozoa of Phryne cincta from a Berlin population (bs) with low crossing-over and from an Alpine population (as) with high crossing-over frequency, egg mortality was ascertained and chromosomal mutation rate determined by examination of the polytene chromosomes of the F1 progeny. - The as stock exhibits a 1.33 times greater radiation sensitivity than the bs stock, both in chromosomal mutation and in egg mortality rates. There is no evidence that factors other than structural ones account for the differences in radiation sensitivity. From inversion length measurements, it was proposed that a reduction of the spiral diameter of the paternal pronucleus chromosomes is responsible for a higher site number and thereby for a greater radiation sensitivity.

Animals↗

PubMed2026

Telomere Length Dynamics as a Biomarker of Individual Radiation Sensitivity and Pneumonitis in Lung Cancer Patients Receiving Thoracic Radiation Therapy.

PURPOSE: Telomere shortening is a biomarker for genome instability and aging, and the vulnerability of telomeric DNA to oxidative damage suggests its potential role in mediating radiation therapy (RT) side effects. This study evaluates telomere length (TL) as a biomarker for clinical radiosensitivity and adverse outcomes in thoracic RT-treated patients. METHODS AND MATERIALS: Patients with cancer receiving thoracic RT (2019-2022) were prospectively enrolled at Brigham and Women's Hospital, Boston, Massachusetts. Peripheral blood mononuclear cells (PBMCs) were collected pre-RT and ≤12 months post-RT. TL was measured using quantitative PCR, and multipathway DNA repair capacity (DRC) was simultaneously assessed by fluorescence multiplex host cell reactivation assays. RT outcomes included patient-reported quality of life and radiation pneumonitis. Linear mixed-effects models were used to analyze TL dynamics; risk prediction models for RT outcomes were evaluated using area under the curve. RESULTS: Pre-RT TL decreased with age (0.44% lower per year; 95% CI, 0.12%-0.77%) and advanced cancer stage (6.87% lower per step increase of stage; 95% CI, 3.45%-10.16%). Radical RT was associated with telomere shortening (3.7% lower; 95% CI, 0.27%-7.07%) in PBMCs, detectable ≤6 months post-RT. Pre-RT TL strongly predicted post-RT changes, and TL dynamics outperformed static measures in predicting symptom burden and radiation pneumonitis. Positive associations were observed between TL and DRC against oxidative lesions, with A:8-oxoG repair capacity mediating 12.8% of RT-induced TL shortening. CONCLUSIONS: Lymphocyte TL can reflect individual radiosensitivity and interact with oxidative damage repair. Longitudinal assessment of TL dynamics provides additional predictive value for adverse RT outcomes compared with static measures. Further studies are needed to fully determine the clinical utility of TL.

Humans↗

PubMed2001

Effect of ionizing radiation on the human brain: white matter and gray matter T1 in pediatric brain tumor patients treated with conformal radiation therapy.

OBJECTIVE: To test a hypothesis that fractionated radiation therapy (RT) to less than 60 Gy is associated with a dose-related change in the spin-lattice relaxation time (T1) of normal brain tissue, and that such changes are detectable by quantitative MRI (qMRI). METHODS: Each of 21 patients received a qMRI examination before treatment, and at several time points during and after RT. A map of brain T1 was calculated and segmented into white matter and gray matter at each time point. The RT isodose contours were then superimposed upon the T1 map, and changes in brain tissue T1 were analyzed as a function of radiation dose and time following treatment. We used a mixed-model analysis to analyze the longitudinal trend in brain T1 from the start of RT to 1 year later. Predictive factors evaluated included patient age and clinical variables, such as RT dose, time since treatment, and the use of an imaging contrast agent. RESULTS: In white matter (WM), a dose level of greater than 20 Gy was associated with a dose-dependent decrease in T1 over time, which became significant about 3 months following treatment. In gray matter (GM), there was no significant change in T1 over time, as a function of RT doses < 60 Gy. However, GM in close proximity to the tumor had an inherently lower T1 before therapy. Neither use of a contrast agent nor a combination of chemotherapy plus steroids had a significant effect on brain T1. CONCLUSION: Results suggest that T1 mapping may be sensitive to radiation-related changes in human brain tissue T1. WM T1 appears to be unaffected by RT at doses less than approximately 20 Gy; GM T1 does not change at doses less than 60 Gy. However, tumor appears to have an effect upon adjacent GM, even before treatment. Conformal RT may offer a substantial benefit to the patient, by minimizing the volume of normal brain exposed to greater than 20 Gy.

Adolescent↗

PubMed1990

Genital tumors among men with psoriasis exposed to psoralens and ultraviolet A radiation (PUVA) and ultraviolet B radiation. The Photochemotherapy Follow-up Study.

Squamous-cell cancer occurs only rarely on the male genitalia. In a 12.3-year prospective study of 892 men in a cohort of patients with psoriasis who had been treated with oral methoxsalen (8-methoxypsoralen) and ultraviolet A photochemotherapy (PUVA), we identified 14 patients (1.6 percent) with 30 genital neoplasms. The standard morbidity ratio (which was used as a measure of the risk of a genital neoplasm) comparing morbidity among patients treated with PUVA with that expected on the basis of population incidence data was 95.7 (95 percent confidence interval, 43.8 to 181.8) for invasive squamous-cell carcinoma of the penis and scrotum, and 58.8 (26.9 to 111.7) for invasive and in situ penile tumors. In patients exposed to high levels of PUVA, the incidence of invasive squamous-cell carcinoma was 286 times that in the general population and 16.3 times that in patients exposed to low levels (P less than 0.001 for both comparisons). After controlling for the level of exposure to PUVA, we found that patients exposed to high levels of ultraviolet B radiation had a risk of genital tumors 4.6 times higher than that in other patients (95 percent confidence interval, 1.4 to 15.1). The strongly dose-dependent increase in the risk of genital tumors associated with exposure to PUVA and ultraviolet B radiation that we observed makes it prudent for men to use genital protection whenever they are exposed to PUVA or other forms of ultraviolet radiation for therapeutic, recreational, or cosmetic reasons.

Adult↗

PubMedDate not supplied

Epidemiological studies on disturbances of human fetal development in areas with various doses of natural background radiation. I. Relationship between incidences of Down's syndrome or visible malformation and gonad dose equivalent rate of natural background radiation.

The relationship between environmental radiation (mSv X a-1) to the gonads and incidences of Down's syndrome and visible malformation was analyzed using Kendall's rank correlation method. The subjects, studied during a 3-yr period (1979-1981), were inhabitants of 46 prefectures in Japan that had various dose rates (mu R/h) of natural background ionizing radiation. Results showed that the natural background very low-dose radiation rate was not a predominant factor responsible for inducing Down's syndrome or other visible malformations.

Background Radiation↗