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A survey of radiation oncologists regarding their radiation physics instruction.

The American Association of Physicists in Medicine, Committee on Training of Radiologists conducted a survey of radiation oncologists requesting information regarding their radiation oncology physics training. General questions were asked of the oncologist regarding their radiation oncology practice such as number of oncologists, number of new patients treated, and the size and type of facility in which the practice is located. The oncologist also responded to questions regarding their educational background. The survey requested the radiation oncologists to answer questions regarding the adequacy and importance of their training in specific areas of radiation physics. The responders indicated that the importance of most physics topics in their clinical practice corresponded to the level of their understanding. The survey indicated that for most radiation oncologists their physics instruction was an important and interesting part of their residency program.

Health Physics↗

Radiation plus local hyperthermia versus radiation plus the combination of local and whole-body hyperthermia in canine sarcomas.

PURPOSE: The purpose of this study was to assess the effect of increasing intratumoral temperatures by the combination of local hyperthermia (LH) and whole body hyperthermia (WBH) on the radiation response of canine sarcomas. METHODS AND MATERIALS: Dogs with spontaneous soft tissue sarcomas and no evidence of metastasis were randomized to be treated with radiation combined with either LH alone or LH + WBH. Dogs were accessioned for treatment at two institutions. The radiation dose was 56.25 Gy, given in 25 2.25 Gy daily fractions. Two hyperthermia treatments were given; one during the first and one during the last week of treatment. Dogs were evaluated after treatment for local recurrence, metastasis, and complications. RESULTS: Sixty-four dogs were treated between 1989 and 1993. The use of LH+WBH resulted in statistically significant increases in the low and middle regions of the temperature distributions. The largest increase was in the low temperatures with median CEM 43 T90 values of 4 vs. 49 min for LH vs. LH + WBH, respectively (p<0.001). There was no difference in duration of local tumor control between hyperthermia groups (p = 0.59). The time to metastasis was shorter for dogs receiving LH + WBH (p = 0.02); the hazard ratio for metastatic disease for dogs in the LH + WBH group was 2.4 (95% confidence interval, 1.2-5.4) with respect to dogs in the LH group. Complications were greater in larger tumors and in tumors treated with LH + WBH, CONCLUSION: The combination of LH + WBH with radiation therapy, as described herein, was not associated with an increase in local tumor control in comparison to use of LH with radiation therapy. The combination of LH + WBH also appeared to alter the biology of the metastatic process and was associated with more complications than LH. We identified no rationale for further study of LH + WBH in combination with radiation for treatment of solid tumors.

Animals↗

Effect of distance to radiation treatment facility on use of radiation therapy after mastectomy in elderly women.

PURPOSE: We sought to study the effect of distance to the nearest radiation treatment facility on the use of postmastectomy radiation therapy (PMRT) in elderly women. METHODS AND MATERIALS: Using data from the linked Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database, we analyzed 19,787 women with Stage I or II breast cancer who received mastectomy as definitive surgery during 1991 to 1999. Multivariable logistic regression was used to investigate the association of distance with receipt of PMRT after adjusting for clinical and sociodemographic factors. RESULTS: Overall 2,075 patients (10.5%) treated with mastectomy received PMRT. In addition to cancer and patient characteristics, in our primary analysis, increasing distance to the nearest radiation treatment facility was independently associated with a decreased likelihood of receiving PMRT (OR = 0.996 per additional mile, p = 0.01). Secondary analyses revealed that the decline in PMRT use appeared at distances of more than 25 miles and was statistically significant for those patients living more than 75 miles from the nearest radiation facility (odds of receiving PMRT of 0.58 [95% CI = 0.34-0.99] vs. living within 25 miles of such a facility). The effect of distance on PMRT appeared to be more pronounced with increasing patient age (>75 years). Variation in the effect of distance on radiation use between regions of the country and nodal status was also identified. CONCLUSIONS: Oncologists must be cognizant of the potential barrier to quality care that is posed by travel distance, especially for elderly patients; and policy makers should consider this fact in resource allocation decisions about radiation treatment centers.

Aged↗

Evidence that most radiation-induced HPRT mutants are generated directly by the initial radiation exposure.

Radiation-induced HPRT mutants are generally assumed to arise directly from DNA damage that is misrepaired within a few hours after X-irradiation. However, there is the possibility that mutations result indirectly from radiation-induced genomic instability that may occur several days after the initial radiation exposure. The protocols that commonly employ a 5-7 day expression period to allow for expression of the mutant phenotype prior to replating for selection of mutants would not be able to discriminate between mutants that occurred initially and those that arose during or after the expression period. To address this question, we performed a fluctuation analysis in which synchronous or asynchronous populations of human bladder carcinoma cells were treated with single doses of X-irradiation. For comparison, radiation was delivered during the expression period, either from an initial dose of 1.0 Gy followed by two 1.0 Gy doses separated by 24 h or from disintegrations resulting from I125dU incorporated into DNA. The mutation frequency observed at the time of replating was used to calculate the average number of mutants in the initial irradiated culture by assuming that the mutants were induced directly at the time of irradiation. Then, this average number was used to calculate the fraction of the irradiated cultures that would be predicted by a Poisson distribution to have zero mutants. There was reasonably good agreement between the predicted poisson distribution and the observed distribution for the cultures that received single doses. Moreover, as expected, when cultures were irradiated during the expression period, the fraction of the cultures having zero mutants was significantly less than that predicted by a Poisson distribution. These results indicate that most radiation-induced HPRT mutations are induced directly by the initial DNA damage, and are not the result of radiation-induced instability during the 5-7 day expression period.

DNA↗

Localized scleroderma in breast cancer patients treated with supervoltage external beam radiation: radiation port scleroderma.

BACKGROUND: An association between systemic scleroderma, radiation, and breast cancer has been recognized. However, localized scleroderma in the radiation port of breast cancer patients has been rarely described. OBJECTIVE: Our purpose was to describe the concurrence of localized scleroderma, supervoltage radiation, and breast carcinoma. METHODS: Patients were prospectively evaluated in a tertiary care cancer center, and the literature was reviewed. RESULTS: We describe six patients with breast cancer in whom localized scleroderma developed within their radiation port. CONCLUSION: Radiation port localized scleroderma can be a sequela of supervoltage radiation therapy in patients with breast cancer. Recognition is important because localized scleroderma can clinically mimic recurrent breast carcinoma.

Breast Neoplasms↗

Environmental remediation by an integrated microwave/UV illumination method. V. Thermal and nonthermal effects of microwave radiation on the photocatalyst and on the photodegradation of rhodamine-B under UV/Vis radiation.

The photocatalyzed degradation (PD) of the cationic rhodamine-B (RhB) dye was examined in aqueous TiO2 dispersions using UV/Vis illumination assisted by microwave radiation (PD/MW). The initial degradation by the PD/MW method is compared to the PD method and to the thermally assisted PD method using conventional heating (PD/TH). Total organic carbon (TOC) assays show that the efficiency of complete mineralization of the dye follows PD/MW > PD/TH > PD > MW. In all cases, microwave radiation alone had no effect on the loss of TOC. The degradation involving microwave radiation was especially efficient when coupled to UV irradiation. By contrast, the extent of degradation of RhB involving suitable excited states through visible irradiation of the dye was rather inefficient when coupled to microwave radiation. Contact angle measurements on the TiO2 photocatalyst particles indicate that microwave radiation also causes an increase in the hydrophobic character of the TiO2 surface, with consequences on the adsorption mode of the dye substrate and thus on the overall mechanism of degradation. Deethylated RhB intermediates were identified by an electrospray ESI ionization mass spectral technique in the positive ion mode and subsequently confirmed by HPLC/absorption spectroscopy. Computer simulations led to estimates of frontier electron densities of all atoms of the RhB structure, affording inferences as to the position of radical attack on RhB. The nitrogen atoms of the dye were all converted to NH4+ ions. The major difference between the thermally assisted PD/TH method and the microwave-assisted PD/MW method showed that nonthermal effects from the microwave radiation impact significantly on the nature of the photocatalyst surface. These effects led to a more efficient photodegradation and mineralization of the dye substrate.

Adsorption↗

The role of radiation-induced apoptosis as a determinant of tumor responses to radiation therapy.

Ionizing radiation is an effective means of killing tumor cells. Approximately 50% of all American cancer patients are treated with radiotherapy at some time during the course of their disease, making radiation one of the most widely used cytotoxic therapies. Currently, much effort is focused on understanding the molecular pathways that regulate tumor cell survival following radiotherapy, with the long term goal of developing novel therapeutic strategies for specifically sensitizing tumors to radiation. At present, there is particular interest in the role of tumor cell apoptotic potential as a regulator of both intrinsic and extrinsic determinants of the response of tumors to radiation therapy. Here we review what is currently known about the role of apoptosis as a mechanism of tumor cell killing by ionizing radiation and the relative contribution of apoptosis to cellular radiosensitivity and the ability to control human cancers using radiotherapy. The following topics will be discussed: (1) radiation-induced apoptosis in normal and malignant cells, (2) clinical findings with respect to apoptosis in human cancers treated with radiotherapy, (3) the contribution of apoptosis to intrinsic radiosensitivity in vitro, (4) the relevance of apoptosis to treatment outcome in experimental tumor models in vivo and (5) the potential of exploiting apoptosis as a means to improve the therapeutic efficacy of radiotherapy.

Journal Article↗

Transcriptional responses to ionizing radiation reveal that p53R2 protects against radiation-induced mutagenesis in human lymphoblastoid cells.

The p53 protein has been implicated in multiple cellular responses related to DNA damage. Alterations in any of these cellular responses could be related to increased genomic instability. Our previous study has shown that mutations in p53 lead to hypermutability to ionizing radiation. To investigate further how p53 is involved in regulating mutational processes, we used 8K cDNA microarrays to compare the patterns of gene expression among three closely related human cell lines with different p53 status including TK6 (wild-type p53), NH32 (p53-null), and WTK1 (mutant p53). Total RNA samples were collected at 1, 3, 6, 9, and 24 h after 10 Gy gamma-irradiation. Template-based clustering analysis of the gene expression over the time course showed that 464 genes are either up or downregulated by at least twofold following radiation treatment. In addition, cluster analyses of gene expression profiles among these three cell lines revealed distinct patterns. In TK6, 165 genes were upregulated, while 36 genes were downregulated. In contrast, in WTK1 75 genes were upregulated and 12 genes were downregulated. In NH32, only 54 genes were upregulated. Furthermore, we found several genes associated with DNA repair namely p53R2, DDB2, XPC, PCNA, BTG2, and MSH2 that were highly induced in TK6 compared to WTK1 and NH32. p53R2, which is regulated by the tumor suppressor p53, is a small subunit of ribonucleotide reductase. To determine whether it is involved in radiation-induced mutagenesis, p53R2 protein was inhibited by siRNA in TK6 cells and followed by 2 Gy radiation. The background mutation frequencies at the TK locus of siRNA-transfected TK6 cells were about three times higher than those seen in TK6 cells. The mutation frequencies of siRNA-transfected TK6 cells after 2 Gy radiation were significantly higher than the irradiated TK6 cells without p53R2 knock down. These results indicate that p53R2 was induced by p53 protein and is involved in protecting against radiation-induced mutagenesis.

Cells, Cultured↗

A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small-cell lung cancer.

BACKGROUND: For patients with locally or regionally advanced non-small-cell lung cancer radiation is the standard treatment, but survival remains poor. We therefore conducted a randomized trial to determine whether induction chemotherapy before irradiation improves survival. METHODS: All the patients had documented non-small-cell cancer of the lung with Stage III disease established by clinical or surgical staging. Eligibility requirements included excellent performance status, minimal weight loss, and visible disease on radiography. Patients randomly assigned to group 1 received cisplatin (100 mg per square meter of body-surface area given intravenously on days 1 and 29) and vinblastine (5 mg per square meter given intravenously on days 1, 8, 15, 22, and 29) and then began radiation therapy on day 50 (60 Gy over a 6-week period). Patients assigned to group 2 received the same radiation therapy but began it immediately and received no chemotherapy. RESULTS: The eligible patients in group 1 (n = 78) and group 2 (n = 77) were comparable in terms of age (median, 60 years), sex, performance status, histologic features, stage of disease, and completeness of radiation therapy. The median survival was greater for those in group 1-13.8 versus 9.7 months (P = 0.0066 by log-rank test). Rates of survival in group 1 were 55 percent after one year, 26 percent after two years, and 23 percent after three years, as compared with 40, 13, and 11 percent, respectively, in group 2. Those in group 1 had a higher incidence of serious infections requiring hospitalization (7 percent, vs. 3 percent in group 2) and severe weight loss (14 percent vs. 6 percent), but there were no treatment-related deaths. CONCLUSIONS: In patients with Stage III non-small-cell lung cancer, induction chemotherapy with cisplatin and vinblastine before radiation significantly improves median survival (by about four months) and doubles the number of long-term survivors, as compared with radiation therapy alone. Since three quarters of the patients still die within three years, however, further improvements in systemic and local therapy are needed.

Antineoplastic Combined Chemotherapy Protocols↗

Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer.

BACKGROUND AND METHODS: We compared the effect of radiotherapy to a pelvic and para-aortic field with that of pelvic radiation and concurrent chemotherapy with fluorouracil and cisplatin in women with advanced cervical cancer. Between 1990 and 1997, 403 women with advanced cervical cancer confined to the pelvis (stages IIB through IVA or stage IB or IIa with a tumor diameter of at least 5 cm or involvement of pelvic lymph nodes) were randomly assigned to receive either 45 Gy of radiation to the pelvis and para-aortic lymph nodes or 45 Gy of radiation to the pelvis alone plus two cycles of fluorouracil and cisplatin (days 1 through 5 and days 22 through 26 of radiation). Patients were then to receive one or two applications of low-dose-rate intracavitary radiation, with a third cycle of chemotherapy planned for the second intracavitary procedure in the combined-therapy group. RESULTS: Of the 403 eligible patients, 193 in each group could be evaluated. The median duration of follow-up was 43 months. Estimated cumulative rates of survival at five years were 73 percent among patients treated with radiotherapy and chemotherapy and 58 percent among patients treated with radiotherapy alone (P=0.004). Cumulative rates of disease-free survival at five years were 67 percent among patients in the combined-therapy group and 40 percent among patients in the radiotherapy group (P<0.001). The rates of both distant metastases (P<0.001) and locoregional recurrences (P<0.001) were significantly higher among patients treated with radiotherapy alone. The seriousness of side effects was similar in the two groups, with a higher rate of reversible hematologic effects in the combined-therapy group. CONCLUSIONS: The addition of chemotherapy with fluorouracil and cisplatin to treatment with external-beam and intracavitary radiation significantly improved survival among women with locally advanced cervical cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Radiation chemistry in the 1990s: pressing questions relating to the areas of radiation biology and environmental research.

This preview discusses the possible future application of ionizing radiation in the study of the free-radical chemistry of some aqueous systems. With respect to the present state of knowledge in the area of chemistry related to radiobiology, ionizing-radiation damage to DNA will continue to be a major focus of radiobiological interest. It is noted that the purine-base, free-radical chemistry is still poorly understood, as is the chemistry of the direct effect of ionizing radiation on DNA. The role of transition metal ions, their interaction with hydrogen peroxide and the superoxide radical are areas of increasing interest, as are other reactions of the superoxide radical. The eventual chemical effects, on DNA, of the reactions of these species resemble those of the action of ionizing radiation and are therefore apt to be studied radiation-chemically. In contaminated water pollution control, procedures termed 'advanced oxidation processes' are gaining in importance. They are based on the action of the .OH radical. Radiation techniques will provide the tools for understanding the underlying reactions better.

Environmental Pollutants↗

Dose response of various radiation detectors to synchrotron radiation.

Accurate dosimetry is particularly difficult for low- to medium-energy x-rays as various interaction processes with different dependences on material properties determine the dose distribution in tissue and radiation detectors. Monoenergetic x-rays from synchrotron radiation offer the unique opportunity to study the dose response variation with photon energy of radiation detectors without the compounding effect of the spectral distribution of x-rays from conventional sources. The variation of dose response with photon energies between 10 and 99.6 keV was studied for two TLD materials (LiF:Mg,Ti and LiF:Mg,Cu,P), MOSFET semiconductors, radiographic and radiochromic film. The dose response at synchrotron radiation energies was compared with the one for several superficial/orthovoltage radiation qualities (HVL 1.4 mm Al to 4 mm Cu) and megavoltage photons from a medical linear accelerator. A calibrated parallel plate ionization chamber was taken as the reference dosimeter. The variation of response with x-ray energy was modelled using a two-component model that allows determination of the energy for maximum response as well as its magnitude. MOSFET detectors and the radiographic film were found to overrespond to low-energy x-rays by up to a factor of 7 and 12 respectively, while the radiochromic film underestimated the dose by approximately a factor of 2 at 24 keV. The TLDs showed a slight overresponse with LiF:Mg, Cu, P demonstrating better tissue equivalence than LiF:Mg, Ti (maximum deviation from water less than 25%). The results of the present study demonstrate the usefulness of monoenergetic photons for the study of the energy response of radiation detectors. The variations in energy response observed for the MOSFET detectors and GAF chromic film emphasize the need for a correction for individual dosimeters if accurate dosimetry of low- to medium-energy x-rays is attempted.

Biophysical Phenomena↗

Preoperative chemotherapy and radiation for advanced esophageal carcinoma: comparison between once a day radiation and hyperfractionation, a single-institution experience.

The purpose of this study was to determine the toxicity and efficacy of single daily fractionation as compared with twice-a-day radiation therapy in combination with chemotherapy for preoperative locally advanced thoracic esophageal carcinoma. A retrospective survey was done of 42 patients undergoing concurrent chemotherapy and radiation for preoperative locally advanced thoracic esophageal carcinoma. Twenty-five patients had 5-fluorouracil ([5-FU]), 1,000 mg/m2/d by continuous infusion, days 1-5, and days 22-26), cisplatin (100 mg/m2 intravenously, days 2 and 22), and radiation to a total dose of 4,500 to 5,040 cGy in 180 cGy/fraction every day. Seventeen patients received 5-FU (300 mg/m2/d by continuous infusion, days 1 and 21), cisplatin (20 mg/m2/d for 1 hour, days 1-5 and days 17-20), vinblastine (1 mg/m2 intravenously, days 1-5 and days 17-21) and accelerated hyperfractionated radiation 150 cGy twice a day to a total dose of 4,500 cGy. Response rate, survival, local regional failure rates, and treatment toxicity of the two groups were compared. Surgery was aborted in one patient and another patient refused surgery in the single daily-fractionation group. All patients underwent surgery in the twice-daily group. Complete response (CR) was noted in 12 patients (52%) in the single daily-fractionation group as compared with 9 patients (52%) in the twice-daily group. The median and 3-year survival were 20 months and 35%, respectively, in the single daily-fractionation group. Corresponding figures were 18 months and 32%, respectively, in the twice-daily group. For the 2 groups combined, a statistically significant improvement in survival was observed among blacks who achieved a CR (31 months) as compared with the ones with residual disease (13.5 months). Local and regional failures were 28% and 17%, respectively, for the single daily-fractionation and twice-daily groups. Distant metastases remained significant in both groups and were 36% (single daily-fractionation) and 41% (twice-daily), respectively. Grades III to IV esophagitis and hematologic toxicity developed in 36% and 64% of patients of the single daily-fractionation and twice-daily groups, respectively. The incidence of late complications was 16% (single daily-fractionation) and 11.7% (twice-daily). Preoperative chemotherapy and radiation is effective to achieve a high pathologic CR. Both radiation therapy fractionation schedules are comparable in efficacy and toxicity. Further investigations should be done to assess whether ethnicity may play a role in the prognosis of esophageal carcinoma.

Adult↗

Lead exposure in radiator repair workers: a survey of Washington State radiator repair shops and review of occupational lead exposure registry data.

Radiator repair workers in Washington State have the greatest number of very elevated (> or =60 microg/dL) blood lead levels of any other worker population. The goals of this study were to determine the number of radiator repair workers potentially exposed to lead; estimate the extent of blood lead data underreporting to the Occupational Lead Exposure Registry; describe current safety and health practices in radiator repair shops; and determine appropriate intervention strategies to reduce exposure and increase employer and worker awareness. Lead exposure in Washington State's radiator repair workers was assessed by reviewing Registry data and conducting a statewide survey of radiator repair businesses. This study revealed that a total of 226 workers in Washington State (including owner-operators and all employees) conduct repair activities that could potentially result in excessive exposures to lead. Approximately 26% of radiator repair workers with elevated blood lead levels (> or =25 microg/dL) were determined to report to Washington State's Registry. This study also revealed a lack of awareness of lead's health effects, appropriate industrial hygiene controls, and the requirements of the Lead Standard. Survey respondents requested information on a variety of workplace health and safety issues and waste management; 80% requested a confidential, free-of-charge consultation. Combining data derived from an occupational health surveillance system and a statewide mail survey proved effective at characterizing lead exposures and directing public health intervention in Washington State.

Data Collection↗

Grating transition radiation: a source of quasimonochromatic radiation.

We have observed transition radiation at optical wavelengths, emitted by 3-13-MeV electrons interacting with a diffraction grating. Near the direction of specular reflection we observed broadband radiation with the same properties as optical transition radiation from a flat surface. In addition, at large angles with respect to this direction and for low angles of incidence of the electrons on the grating surface, we observed the emission of quasimonochromatic radiation. This grating transition radiation may offer an alternative method for production of quasimonochromatic radiation in the far-infrared to mm wavelength range.

Journal Article↗

Transformation in the use of radiation therapy of Hodgkin lymphoma: new concepts and indications lead to modern field design and are assisted by PET imaging and intensity modulated radiation therapy (IMRT).

The role of radiation therapy (RT) in Hodgkin lymphoma has changed substantially; it has evolved from a first-line comprehensive single agent into a complementary adjuvant following chemotherapy. Yet, the significant contribution of adding radiotherapy has repeatedly been confirmed by recent information from several prospective randomized trials in early stage patients (CCG, Canada NCIC, and EORTC/GELA H9F). In a recent study that included patients of all stages adding radiotherapy impacted significantly on overall survival. Even in advanced-stage disease, in patients with less than CR, and/or bulky disease or in programs that use short-course chemotherapy (e.g. Stanford V) involved-field radiation therapy (IFRT) remained essential. Randomized studies and most recently the GHSG HD 10 and HD 11 documented excellent results with low-dose IFRT of only 20 Gy in both early stage and in intermediate-stage patients. It is now standard of care to use IFRT rather than the extended radiation fields of the past (mantle, inverted Y, and STLI/TLI). Even smaller volumes than IFRT, such as 'lymph-node fields' are advocated by paediatrics groups and are under consideration for future adults treatment programs. This change in RT concept has been motivated by need to reduce normal tissue exposure in order to markedly lessen the risk of late complications. The small fields of current radiotherapy allow more conformal and innovative approaches that have not been technically feasible in the past. They also mandate better targeting. Both the accuracy and the confirmality of 'min-radiation' are augmented, by using new advances in imaging, treatment planning, and new radiation delivery systems. The PET/CT/Simulator integrated hardware with innovative software allows more accurate PET and CT (or MRI) parallel volume contouring, radiation 'dose painting' (dose tailored to PET residual activity) and field 'sculpting'. Introducing intensity modulated radiotherapy technology (IMRT)--a technology that was originally designed for small tumors treated with very high doses--to the field of lymphoma provides safer and more accurate radiotherapy to selected patients with very bulky residual disease and permits re-irradiation of relapsed disease.

Combined Modality Therapy↗

Ultraviolet A radiation (320-400 nm) protects hairless mice from immunosuppression induced by ultraviolet B radiation (280-320 nm) or cis-urocanic acid.

T cell-mediated immune function, here measured as the contact hypersensitivity reaction, is readily suppressed by moderate exposure of mice to ultraviolet B (UVB) or solar-simulated radiation (SSUV), or by topical application of cis-urocanic acid. The effect of ultraviolet A (UVA) radiation on immune function has been unclear. Here we have demonstrated that when UVA radiation from a fluorescent tube source was rigorously filtered to remove contaminating UVB radiation, it was immunologically innocuous at physiologically relevant doses. Furthermore, we have found that mice exposed to UVA radiation, either immediately after, or up to 24 h before, immunosuppressive treatment with either UVB radiation, SSUV or cis-urocanic acid, became refractory to the immunosuppression and retained more normal contact hypersensitivity. A greater UVA exposure reversed the immunosuppression more effectively. The results suggest that there are immunologically significant interactions between UV wavebands, and that UVA exposure may induce a relatively long-lived immunoprotective photoproduct, as yet unidentified, that can inhibit the activity of epidermal cis-urocanic acid and thus provide protection from photoimmunosuppression.

Animals↗

Prolonged antiplatelet therapy to prevent late thrombosis after intracoronary gamma-radiation in patients with in-stent restenosis: Washington Radiation for In-Stent Restenosis Trial plus 6 months of clopidogrel (WRIST PLUS).

BACKGROUND: Intracoronary gamma-radiation reduces recurrent in-stent restenosis. Late thrombosis (>30 days after radiation therapy) is identified as a serious complication. The Washington Radiation for In-Stent Restenosis Trial (WRIST) PLUS, which involved 6 months of treatment with clopidogrel and aspirin, was designed to examine the efficacy and safety of prolonged antiplatelet therapy for the prevention of late thrombosis. METHODS AND RESULTS: A total of 120 consecutive patients with diffuse in-stent restenosis in native coronary arteries and vein grafts with lesions <80 mm underwent percutaneous coronary transluminal angioplasty, laser ablation, and/or rotational atherectomy. Additional stents were placed in 34 patients (28.3%). After the intervention, a closed-end lumen catheter was introduced into the artery, a ribbon with different trains of radioactive (192)Ir 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 6 months and followed angiographically and clinically. All patients but one tolerated the clopidogrel. The late occlusion and thrombosis rates were compared with the gamma-radiation-treated (n=125) and the placebo patients (n=126) from the WRIST and LONG WRIST studies (which involved only 1 month of antiplatelet therapy). At 6 months, the group receiving prolonged antiplatelet therapy had total occlusion and late thrombosis rates of 5.8% and 2.5%, respectively; these rates were lower than those in the active gamma-radiation group and similar to those in the placebo historical control group. CONCLUSIONS: Six months of clopidogrel and aspirin and a reduction in re-stenting for patients with in-stent restenosis treated with gamma-radiation is well tolerated and associated with a reduction in the late thrombosis rate compared with a similar cohort treated with only 1 month of clopidogrel and aspirin.

Aged↗