Biological aspects of neuroblastomas identified by mass screening in Quebec.

BACKGROUND: Neuroblastoma has several characteristics that suggest that preclinical diagnosis might improve outcome. Therefore, the Quebec Neuroblastoma Screening Project was undertaken from 1989 to 1994 to examine infants at 3 weeks and 6 months by measuring urinary catecholamine metabolites. PROCEDURE: Over the 5-yr period, 45 tumors were detected by screening, 20 were identified clinically prior to the third week, and 64 were identified clinically at a later time. We analyzed available tumors for Shimada histopathology, tumor ploidy, MYCN copy number and serum ferritin. RESULTS: Of the tumors detected by screening, only 2 of 45 tested had unfavorable histology, 2 of 45 had diploid or tetraploid DNA content, 0 of 43 had MYCN amplification, and 4 of 44 had elevated serum ferritin. All of these patients are alive and well. The 20 patients detected prior to the 3-week screen had similar biological characteristics. In contrast, of the patients detected clinically after 3 weeks of age, 19 of 51 testedhad unfavorable histology, 25 of 66 had diploid or tetraploid tumors, 12 of 56 had MYCN amplification, and 14 of 54 had elevated ferritin. CONCLUSIONS: The difference between the screened and clinically detected cases was highly significant for each biological variable. Preliminary data on other biological variables, such as neurotrophin expression and allelic loss on 1 p in these patients are consistent with the above findings. These data suggest that mass screening for neuroblastoma at or before 6 months of age detects almost exclusively tumors that have favorable biological characteristics, many of which might have regressed spontaneously. Thus, continued mass screening for neuroblastoma at 6 months is unlikely to accomplish its intended goal, and should probably be discontinued.

Cyclophosphamide-based, seven-drug hybrid and low-dose involved field radiation for the treatment of childhood and adolescent Hodgkin disease.

PURPOSE: The outlook for children and adolescents with Hodgkin disease (HD) is excellent with combined modality therapy. However, the long-term toxicities of multiagent therapy and radiation therapy remain of concern for these patients with curable disease. In an attempt to reduce long-term toxicities while preserving excellent cure rates, we developed a combined-modality protocol using a modified seven-drug hybrid and low-dose (2,000 cGy) involved field radiation therapy (RT). The hybrid used cumulative doses of alkylating agents and anthracyclines that were lower than those used in previous four-drug regimens and substituted a less leukemogenic agent, cyclophosphamide, for nitrogen mustard. PATIENTS AND METHODS: From 1991 through 1994 a cyclophosphamide, vincristine, procarbazine, and prednisone/adriamycin, bleomycin, and vinblastine hybrid was used to treat 29 patients with HD. Median age was 12 years (range 6-16 yrs). Patients who were postpubertal with early stage disease as determined by surgical staging were excluded. Treatment consisted of four cycles of therapy for stages I and IIA, six cycles for stages IIB and III, and eight cycles for stage IV. Twenty-two patients also received low-dose RT to areas of bulky disease. RESULTS: Twenty-eight patients (97%) had a complete response to chemotherapy. Five patients experienced relapse; two died from disease 27 and 29 months after initial diagnosis; three received additional therapy and are alive with no evidence of disease. Follow-up for all other patients is a median of 56 months (range 24-78 mos) from cessation of therapy and all have remained disease-free. At 5 years follow-up, actuarial disease-free survival is 82%, and the overall survival is 93%. There have been no clinically significant cardiac or pulmonary toxicities and no secondary malignancies. CONCLUSIONS: This therapy has resulted in 5-year overall survival and disease-free survival rates similar to regimens using higher doses of alkylating agents, anthracyclines, and radiation. Longer follow-up will be necessary to fully evaluate disease-free survival, organ damage, and quality of life.

Enhancement of radiation effects by combined docetaxel and carboplatin treatment in vitro.

This study was designed to evaluate the combination of docetaxel (Taxotere) and carboplatin for radiopotentiation in vitro. H460 human lung carcinoma cells were treated with docetaxel (or paclitaxel) for 1 h and rinsed. After 24 h, the cells were treated with carboplatin for 1 h, irradiated, and colony forming ability was assesed. Using various doses of docetaxel with 100 microM carboplatin, the dose enhancement ratio (D.E.R.) for drugs only was 1.26. When 25 nM docetaxel was used with various doses of radiation, the radiation D.E.R. was 1.41. With all three agents combined, and after normalization for combined drug effects, the radiation D.E.R. was 1.55. Similar values were obtained using paclitaxel with these agents. Significant redistribution of cells into the radiosensitive G2/M phase was observed using a dose of paclitaxel (750 nM), which also caused radiation enhancement. However, an equally cytotoxic dose of docetaxel (25 nM) did not result in any cell cycle redistribution; this phenomenon was only observed at higher doses. This study shows that the combination of docetaxel and carboplatin enhance the effects of radiation in vitro more effectively than either drug seperately. In addition, our data show that the mechanism of radiopotentiation by docetaxel probably does not involve a G2/M block in H460 cells.