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Biomedical subjects

H Kooy

Publications and source records attributed to H Kooy.

11 recordsLinked to original sources

Proton beam therapy.

Conventional radiation therapy directs photons (X-rays) and electrons at tumours with the intent of eradicating the neoplastic tissue while preserving adjacent normal tissue. Radiation-induced damage to healthy tissue and second malignancies are always a concern, however, when administering radiation. Proton beam radiotherapy, one form of charged particle therapy, allows for excellent dose distributions, with the added benefit of no exit dose. These characteristics make this form of radiotherapy an excellent choice for the treatment of tumours located next to critical structures such as the spinal cord, eyes, and brain, as well as for paediatric malignancies.

Adult↗

Radiosurgery in the management of pediatric brain tumors.

OBJECTIVE: To describe the outcome of pediatric brain tumor patients following stereotactic radiosurgery (SRS), and factors associated with progression-free survival. METHODS: We reviewed the outcome of 90 children treated with SRS for recurrent (n = 62) or residual (n = 28) brain tumors over a 10-year period. Median follow-up from SRS was 24 months for all patients and 55.5 months for the 34 patients currently alive. RESULTS: The median progression-free survival (PFS) for all patients was 13 months. Median PFS according to tumor histology was medulloblastoma = 11 months, ependymoma = 8.5 months, glioblastoma and anaplastic astrocytoma = 12 months. Median PFS in patients treated to a single lesion was 15.4 months. No patient undergoing SRS to more than 1 lesion survived disease free beyond 2 years. After adjusting for histology and other clinical factors, SRS for tumor recurrence (RR = 2.49) and the presence of > 1 lesion (RR = 2.3) were associated with a significantly increased rate of progression (p < 0.05). Three-year actuarial local control (LC) was as follows: medulloblastoma = 57%, ependymoma = 29%, anaplastic astrocytoma/glioblastoma = 60%, other histologies = 56%. Nineteen patients with radionecrosis and progressive neurologic symptoms underwent reoperation after an interval of 0.6-62 months following SRS. Pathology revealed necrosis with no evidence of tumor in 9 of these cases. CONCLUSION: SRS can be given safely to selected children with brain tumors. SRS appears to reduce the proportion of first failures occurring locally and is associated with better outcome when given as a part of initial management. Some patients with unresectable relapsed disease can be salvaged with SRS. SRS to multiple lesions does not appear to be curative. Serious neurologic symptoms requiring reoperation is infrequently caused by radionecrosis alone.

Adolescent↗

A clinical method for real-time dosimetric guidance of transperineal 125I prostate implants using interventional magnetic resonance imaging.

PURPOSE: The clinical utility of an interventional magnetic resonance (IMR)-guided implant technique with real-time dosimetric feedback is presented. METHODS AND MATERIALS: The work was carried out at a IMR unit at Brigham and Women's Hospital. Planning and dosimetric feedback were provided by a software system that provides an interface to the IMR images, anatomy demarcation, template registration, dose calculation engine for planning, and evaluating the implant. Planning during the procedure permits the incorporation of actual needle trajectories in the dose calculations. RESULTS: Fifteen patients were planned in the treatment position. During source placement, actual needle locations were incorporated into the dose calculations. After accounting for the observed needle trajectories of the planned needles, 14 of 15 patients (93%) required additional sources to achieve the desired coverage of the target volume. CONCLUSION: A brachytherapy implant procedure which provides clinically significant advances has been implemented. Specifically, the planning system allows dosimetric validation of the needle placement. This procedure is effective in delivering brachytherapy to the target volume and assuring that the implant is delivered in accordance with the preplan. The dosimetric feedback could be incorporated in ultrasound-guided implants.

Brachytherapy↗

The prevention of radiosurgery-induced nausea and vomiting by ondansetron: evidence of a direct effect on the central nervous system chemoreceptor trigger zone.

Nausea and emesis are significant side effects in patients undergoing stereotactic radiosurgery for brain lesions in the region of the chemoreceptor trigger zone (area postrema of the brain). Even with the current antiemetic treatment (prochlorperazine +/- corticosteroids), those side effects remain significant. The purpose of this study is twofold: [1] to evaluate the efficacy of ondansetron in inhibiting nausea and emesis in stereotactic radiosurgery patients and [2] to demonstrate that ondansetron's locus of action is the central nervous system (CNS) chemoreceptor trigger zone in the area postrema. In a pilot study, 10 patients receiving > or = 350 cGy in a single fraction of radiosurgery to the region of the area postrema received 32 mg ondansetron iv 1 hour prior to treatment +/- corticosteroids. In a retrospective analysis these results were compared to those of patients with similar features (and matched for radiation dose to the area postrema and the dose of corticosteroids) who received prochlorperazine +/- corticosteroids. Nine of 10 patients in the ondansetron group had no nausea or emesis within 48 hours after treatment; one patient experienced one episode of emesis. In the prochloreperazine group, eight patients had symptoms, three patients needed hospitalization or a physician's care for emesis within 24 hours, and five had nausea with no specific treatment. These preliminary results suggest that ondansetron is a safe and efficient drug to prevent nausea and emesis in this patient group. The precise mechanism of action of ondansetron in these patients is unknown, but is likely due to the drug's serotonin-blocking effect within the CNS. A randomized, prospective study has been started at our institution to confirm these preliminary results.

Adult↗

Influence of long-term ethanol treatment on in vitro biotransformation of benzo(a)pyrene in microsomes of the liver, lung and small intestine from male and female rats.

The influence of long-term ethanol exposure of rats on the microsomal biotransformation of benzo(a)pyrene [B(a)P] was studied. Male and female Wistar rats received an increasing amount of ethanol in their drinking water: percentages rose to 15% (w/v) in 3 weeks. The ethanol content was kept at a concentration of 15% for another 3 weeks. Livers, lungs and intestinal epithelial cells of the rats were then isolated and microsomal fractions prepared. In all organs, the metabolite most formed was 3-hydroxy-B(a)P. In the liver, males showed significantly higher B(a)P hydroxylase activity than females. On the basis of experiments using monoclonal antibodies, a significant part of the B(a)P biotransformation in male rat liver microsomes can be attributed to the male specific P4502C11. In the lung and intestine, there were no significant differences between the sexes. In the liver, ethanol treatment significantly decreased the microsomal formation of phenolic metabolites. In microsomes of intestinal epithelial cells, ethanol treatment enhanced the formation of phenols and diols. In conclusion, ethanol consumption by rats in moderate amounts leads to an alteration in the microsomal biotransformation of B(a)P. Effects are most prominent in the liver, where the formation of phenols is significantly decreased.

Animals↗

Detection of HIV antibodies in saliva as a tool for epidemiological studies.

OBJECTIVE: To evaluate the use of saliva specimens for the detection of HIV antibodies among high-risk groups in epidemiological studies. DESIGN: Testing of saliva specimens collected by different methods from individuals with known HIV status. The most reliable method was examined for its usefulness in a field study among a high-risk group. METHODS: Saliva samples were obtained either by using a cotton-wool roll ('Salivette') or as 'whole saliva'. HIV antibodies were determined using commercial enzyme-linked immunosorbent assays (ELISA). Confirmation was performed using a line immunoassay or an immunoblot assay. RESULTS: In 'Salivette' samples, HIV antibodies were detected by ELISA in seven out of 22 seropositive individuals. In contrast, testing of 'whole saliva' samples from 79 HIV-seropositive and 115 HIV-seronegative individuals resulted in a 100% correlation with HIV serum status. The positive reaction of 20 'whole saliva' specimens was confirmed in a line immunoassay, whereas in an immunoblot assay only seven specimens were positive, one negative, and 12 indeterminate. In an HIV prevalence study among drug users, 395 'whole saliva' samples were tested in two different ELISA. Both assays showed complete agreement in detecting 58 positive and 337 negative samples. All positive samples were confirmed by the line immunoassay. CONCLUSION: Our study demonstrates that 'whole saliva' specimens are a good alternative to blood samples in epidemiological studies of HIV prevalence in high-risk groups.

Adult↗

Variables associated with the development of complications from radiosurgery of intracranial tumors.

Between 5/21/86 and 11/1/89, we treated 64 recurrent or inoperable intracranial tumors in 60 patients (40 primary, 24 metastatic) with stereotactic radiosurgery using a modified 6 MeV linear accelerator at the Joint Center for Radiation Therapy. Patients were followed until death or 1/1/90. The median follow-up was 8 months (2-43 months). Fourteen patients experienced complications from 12 hours to 7 months (median 3 months, but only two patients more than 4 months) following radiosurgery. To determine variables related to complication, we calculated integral dose-volume histograms for 61/64 lesions and the surrounding CT-defined normal tissue. We excluded 16 lesions in 15 patients for follow-up less than 4 months (12 patients) or insufficient treatment information (3 patients). The variables for which higher values were associated with significantly more toxicity in a univariate score test were: a) tumor dose inhomogeneity (p less than 0.00001), b) maximum tumor dose (p = 0.00002), c) number of isocenters (p = 0.00002), d) maximum normal tissue dose (p = 0.00005) and e) tumor volume (p = 0.0001). These variables were all highly correlated with tumor dose inhomogeneity (coefficients of rank correlation 0.75-0.81). Tumor dose inhomogeneity had a much higher loglikelihood in a logistic model than any other single variable and a higher loglikelihood than any other two variables combined. None of the 21 patients with metastatic lesions experienced a complication. When we excluded the metastatic lesions, the above five variables remained significant in univariate tests. The mean tumor dose, number of treatment arcs, total degrees of arc, tumor location, previous radiotherapy, tumor geometry, pretreatment performance status, collimator size, and age were not significantly associated with toxicity. We conclude that radiosurgery of intracranial tumors is associated with a low risk of complications for lesions less than 10cc treated with a single isocenter to maximum tumor doses less than 25 Gy with tumor dose inhomogeneity less than 10 Gy, but that treatment of larger lesions will require new treatment strategies which reduce the tumor dose inhomogeneity associated with multiple isocenter treatments.

Brain Neoplasms↗

Early breast cancer: predictors of breast recurrence for patients treated with conservative surgery and radiation therapy.

The identification of factors associated with breast recurrence following conservative surgery (CS) and radiation therapy (RT) is of potential use in refining patient selection criteria and treatment technique. In an attempt to define such factors we examined the relationship between various clinical, pathologic and treatment characteristics and the likelihood of breast recurrence in 783 patients with clinical stage I or II breast cancer treated between July 1968 and December 1982. Treatment consisted of complete gross excision of the primary tumor and RT to a total dose of at least 60 Gy to the primary site. During this period, pre-treatment mammograms and detailed histologic assessment of the margins of resection were not routinely performed. Median follow-up for surviving patients was 80 months. Thirteen patients (1.6%) were lost to follow-up. Ninety-one patients (12%) have developed a breast recurrence, corresponding to 5- and 10-year actuarial rates of 10 and 18%, respectively. The major feature associated with breast recurrence was the presence of an "extensive intraductal component" (EIC+). An EIC+ tumor was seen in 28% of evaluable cases with infiltrating ductal carcinoma and accounted for 60% of breast recurrences. Forty-three of 166 patients (26%) with EIC+ tumors developed a breast recurrence compared with 29 of 418 patients (7%) without an EIC (EIC-) (p = 0.0001). The 5-year actuarial rates of breast relapse were 24 and 6%, respectively (p = 0.0001). Very young age (defined as 34 years of age or younger) was also a significant factor associated with the risk of breast recurrence. Very young patients comprised 8% of the patient population and accounted for 16% of breast recurrences. Fifteen of 61 very young patients (25%) developed a breast recurrence compared with 76 of 722 older patients (11%) (p = 0.001). The corresponding 5-year actuarial rates of breast recurrence were 21 and 9% (p = 0.005). None of the other clinical or pathological factors examined by univariate analysis were significantly correlated with recurrence in the breast. A multivariate model of site of first failure (polychotomous logistic regression) also showed that EIC+ tumors and very young age were the main factors associated with a high relative risk of breast recurrence. We conclude that EIC+ tumors and very young age are associated with a high risk of breast recurrence for patients treated with limited excision prior to RT.

Actuarial Analysis↗