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Biomedical subjects

M G Haddock

Publications and source records attributed to M G Haddock.

28 records · Page 2Linked to original sources
PubMed1997

Intraoperative irradiation: current and future status.

Intraoperative radiation therapy (IORT) in its broadest sense refers to the delivery of irradiation at the time of an operation. This article will discusses the rationale for and results of both intraoperative electron radiation therapy and intraoperative high dose rate brachytherapy when used in conjunction with surgical exploration and resection and external beam radiation therapy and chemotherapy. Both IORT methods evolved with similar philosophies as an attempt to achieve higher effective doses of irradiation while dose limiting structures are surgically displaced.

Brachytherapy↗
PubMed1996

Histologically confirmed pineal tumors and other germ cell tumors of the brain.

BACKGROUND: This study examined the outcome of patients with histologically confirmed pineal region tumors. METHODS: One hundred thirty-five patients with histologically confirmed pineal tumors and other germ cell tumors of the brain were evaluated retrospectively. The pineal parenchymal tumors (PPTs) included 15 pineoblastomas (PB), 2 mixed PPTs, 4 PPTs with intermediate differentiation, and 9 pineocytomas. The germ cell tumors included 48 germinomas, 26 mixed germ cell tumors, 11 mature teratomas, 9 immature teratomas, 6 malignant teratomas, 2 yolk sac tumors, and 3 choriocarcinomas. Patients were treated with various combinations of chemotherapy, radiotherapy, and surgery. The duration of follow-up ranged from 0.25 to 37.3 years, with a median follow-up of 5.3 years. RESULTS: The 5-year patient survival rate was 86% for those with mature teratomas; 86% with pineocytomas; 80% with germinomas; 67% with immature teratomas; 49% with PPTs, excluding pineocytomas; 38% with mixed germ cell tumors; and 17% with other germ cell histologies (P = 0.0001). The delivery of > 44 Gray (Gy) to germinomas and > 50 Gy to PPTs and nongerminomatous germ cell tumors (NGGCTs) other than mature and immature teratomas was associated with improved survival. A greater extent of resection was associated with a higher rate of survival in all patients with NGGCTs. The administration of chemotherapy was associated with improved survival in those patients with NGGCTs other than mature and immature teratomas. CONCLUSIONS: Prognosis was dependent on tumor type. Obtaining a tissue diagnosis made it possible to tailor therapy according to tumor type and potentially improve the survival of patients. Survival was dependent on the dose of radiation administered to patients with PPTs, germinomas, and NGGCTs other than mature and immature teratomas. More extensive resection and the use of chemotherapy were also associated with improved survival in subgroups of patients with NGGCTs. Treatment recommendations are described in detail in the article.

Adolescent↗
PubMed1996

Nongerminomatous germ cell tumors of the brain.

PURPOSE: This analysis was performed to determine the clinical outcome of patients with primary nongerminomatous germ cell tumors of the brain. The efficacy of various treatment options was evaluated. METHODS AND MATERIALS: A total of 57 patients with primary nongerminomatous germ cell tumors of the brain were identified. Patient-related data were collected and analyzed retrospectively. Follow-up in surviving patients ranged from 3 to 243 months (median follow-up 36). Survival and failure rates were determined using the Kaplan-Meier method, and differences between the survival curves were evaluated using either the log rank test or the Wilcoxon test. RESULTS: The 3-year survival rate was 86% for patients with mature teratomas, 67% for patients with immature teratomas, 44% for patients with mixed germ cell tumors, and 13% for patients with the other histologic types (p = 0.02). The 3-year survival rate was 0% for patients having biopsies alone, 32% for patients having subtotal resections, and 73% for patients having gross total resections (p = 0.0001). Patients with tumors other than mature or immature teratomas were evaluated for possible relationships between the administration of chemotherapy or radiotherapy and survival. Patients who received chemotherapy had a 3-year survival rate of 56% compared to 8% for those patients who did not receive chemotherapy (p = 0.0001) Patients who received radiotherapy had a 3-year survival rate of 46% compared to 11% for those patients who did not receive radiotherapy (p = 0.0015). CONCLUSION: The survival of patients with primary nongerminomatous germ cell tumors of the brain is dependent on tumor histology and the extent of surgical resection. Patients with tumors other than mature or immature teratomas appear to benefit from the administration of chemotherapy and radiotherapy.

Brain Neoplasms↗
PubMed1996

Indications for and results of irradiation +/- chemotherapy for rectal cancer.

With mobile rectal cancers, surgery alone is insufficient treatment for most patients with high-risk factors of tumour extension beyond the rectal wall, node involvement, or both in conjunction. While single modality adjuvant treatment with pre- or postoperative irradiation can reduce the incidence of local relapse, a statistically significant impact on survival has not been achieved. Combined modality postoperative chemoirradiation has resulted in both improved disease control (local and distant) and improved survival (disease free and overall). Randomized trials are underway in high-risk patients to determine the most optimal combinations of postoperative chemoirradiation and to compare preoperative versus postoperative chemoirradiation. Standard therapy with surgery, external irradiation, and chemotherapy is often unsuccessful for patients with locally advanced primary cancers that are unresectable for cure or locally recurrent cancers. When intraoperative electron irradiation is combined with standard treatment, encouraging trends are seen with regard to improvements in local control and survival in separate analyses from the Mayo Clinic and the Massachusetts General Hospital. More standard use of systemic therapy is needed as a component of treatment, however, in view of high rates of systemic failure in spite of the locally aggressive treatment regimens.

Antineoplastic Agents↗
PubMed1995

Assessing the interaction of irradiation with etoposide or idarubicin.

OBJECTIVE: To compare the interactions of two topoisomerase II inhibitors, etoposide and idarubicin, with irradiation. DESIGN: Two mathematical modeling systems were used to assess the interactions. METHODS AND RESULTS: Hamster lung fibroblast cells (V79) were exposed to etoposide or idarubicin for 24 hours before or immediately after irradiation. Post radiation treatment with etoposide or idarubicin resulted in radiosensitization, as demonstrated by a decrease in the mean inactivation dose. Exposure to either drug before irradiation resulted in no radiosensitization. The first mathematical modeling system used was isobologram analysis. This analysis revealed a synergistic interaction if etoposide exposure followed irradiation. The interaction from the combination of irradiation and preradiation etoposide was within the envelope of addivity. Irradiation and postradiation idarubicin exposure also resulted in an interaction within the envelope of addivity, whereas preradiation idarubicin exposure resulted in a slightly less than additive interaction. Next, analyses were performed by the median effect principle. Synergistic interactions were demonstrated for combinations of etoposide and irradiation as well as idarubicin and irradiation. Synergistic interactions were more likely when drug exposure (either idarubicin or etoposide) followed irradiation. Experiments at various ratios of radiation dose to drug concentration showed that the likelihood of a synergistic interaction increased as the drug concentration increased relative to the radiation dose. CONCLUSION: The interaction of irradiation with topoisomerase II-reactive agents should be further explored in human tumor cell lines.

Animals↗
PubMed1994

Etoposide-resistance in the multidrug-resistant LZ-8 cells.

The multidrug-resistant LZ-8 cells were found to exhibit marked resistance to etoposide compared to wild-type, parental V79 cells. The multidrug resistant phenotype did not significantly contribute to this etoposide-resistance. Following exposure of LZ-8 cells and V79 cells to equivalent concentrations of etoposide, there was a dramatic reduction in the number of etoposide-induced stabilized DNA-topoisomerase II complexes in the LZ-8 cells compared to V79 cells, however, this reduction was not found when nuclei isolated from LZ-8 and V79 cells were exposed to equivalent concentrations of etoposide. These results suggest that cytoplasmic factors are involved in the etoposide-resistance of LZ-8 cells.

Animals↗