Long-term results of accelerated radiation treatment for advanced head and neck cancer.

BACKGROUND AND PURPOSE: This report presents long-term follow-up data from a prospective but unrandomized trial of a continuous 3.5-week course of accelerated radiation treatment (ART) used as primary treatment for patients with loco-regionally advanced head and neck cancer. MATERIALS AND METHODS: Ninety-three patients in three centres in New Zealand and Australia were treated with ART (59.40 Gy in 33 fractions over 24-25 days). Their disease originated from three anatomical regions (oral cavity, 35 patients; pharynx, 31 patients; larynx, 27 patients). Seventy-nine of these patients had stage III or IV cancers. RESULTS: Follow-up ranged from 68 to 203 months (median 139 months). Loco-regional (LR) failure occurred in 52 patients leading to a 10-year actuarial expectation of LR control of 38%. The actuarial expectation of LR control at 10 years was highly dependent on stage and for stage III, IVA and IVB patients it was 57+/-8.1%, 32+/-1.7% and 7+/-0.5%, respectively. Multivariate analysis could not confirm an independent impact of primary site or histological differentiation on LR failure. Two patients died of acute toxicity of treatment and six patients developed grade 3/4 late complications affecting soft tissues only, yielding an actuarial expectation of complications of this severity at 5 years of 9%. No cases of osteoradionecrosis or myelitis were observed. CONCLUSION: This ART, which has proved easy to use at a number of large and small centres, has produced encouraging long-term LR control at a cost of limited soft tissue morbidity.

Orchidectomy prior to definitive radiotherapy for localized prostatic cancer.

PURPOSE: To identify potential survival benefits of cytoreductive orchidectomy performed prior to definitive radiation for localized prostate cancer. METHODS AND MATERIALS: Between 1977-1988, all patients with localized prostatic cancer from the Wellington Region received definitive radiotherapy (n = 200). One referring urologist Peter M. Meffen (P.M.M.) had commenced a program of prior orchidectomy followed by definitive radiation treatment (median time to radiation therapy was 5 months, n = 30). RESULTS: Five-year overall survival (OS) and relapse-free survival (RFS) for each stage were Stage A 82%, and 82%; Stage B 75%, and 61%; Stage C 57%, and 38%, respectively. Ten-year OS and RFS for each stage were Stage A 78%, and 72%; Stage B 51%, and 18%; Stage C 32% and 0%, respectively. Multivariate analysis identified prior orchidectomy treatment and histological grade as independently significant prognostic factors for OS and RFS. Factors influencing RFS were clinical stage, prior orchidectomy, and histological grade. Prior orchidectomy was associated with an increase in OS at 5 years when compared to those patients receiving radiotherapy alone, 86% vs. 69%, and maintained at 10 years, 82% vs. 46% (p < 0.05). The two groups were comparable by stage, histological grade, and age. There were no changes in the referral pattern during the study period. CONCLUSIONS: Our results suggest that prior cytoreduction by orchidectomy has a beneficial effect on OS and RFS for patients with localized prostate cancer. It is unclear whether survival benefits are due to the cytoreductive therapy, the adjuvant therapy, or a combination of both. Further study in this area is warranted, ideally in the form of randomized prospective clinical trials.

Secretion of anti-parasite substances and leukotrienes from ovine gastrointestinal tissues and isolated mucosal mast cells.

The presence of larval migration inhibitory (LMI) compounds in the gastrointestinal mucus of nematode resistant sheep has been shown previously to be associated with increased numbers of gastrointestinal mucus of nematode resistant sheep has been shown previously to be associated with increased numbers of gastrointestinal mucosal mast cells (MMC) and globule leukocytes (GL). This experiment was designed to determine if LMI compounds were secreted by MMC/GL in response to nematode antigenic challenge and if so, could secretion account for levels observed in mucus. Romney sheep were immunized by repeated cycles of infection with Trichostrongylus colubriformis or Haemonchus contortus larvae and anthelmintic treatment. After slaughter, gastrointestinal tissue was taken for examination of histology and mucus anti-parasite activity. Segments of small intestine were ligatured to form sacs which were incubated with exsheathed nematode larvae or larval excretory/secretory antigens. Tissue slices from small intestine or abomasum were also incubated with nematode larvae or antigens. After homologous challenge, levels of leukotrienes secreted into small intestinal tissue sacs were significantly higher than levels in heterologously challenged sacs or unimmunized sheep intestinal sacs challenged with larvae of any nematode species (279.4 +/- 33.7, 141.0 +/- 27.8 and 39.5 +/- 15.2 ng h-1 respectively). Tissue slices gave a similar pattern of leukotriene secretion. LMI activity was also significantly elevated in intestinal sacs from immunized sheep challenged homologously with nematode larvae or antigen (64 +/- 10 and 68 +/- 14% respectively cf. heterologous challenge 32 +/- 10% and unimmunized sheep sacs 15 +/- 6%). Histological examination of abomasal and small intestinal sections showed that immunized sheep had significantly greater numbers of MMC/GL than unimmunized sheep. MMC/GL isolated and purified from immunized sheep secreted leukotrienes and compounds having LMI activity when cultured with homologous nematode larvae or antigens. Secretion of leukotrienes and molecules having LMI activity from MMC/GL could account for the levels of these substances observed in small intestine mucus.

The effects of anthelmintics on ovine larval nematode parasite migration in vitro.

The anthelmintics ivermectin, levamisole, morantel tartrate and thiabendazole all inhibited, in vitro, the motility of third stage larvae (L3) of Trichostrongylus colubriformis. The bioassay, based on the inhibition of L3 migration from agar gels, yielded sigmoid dose-response curves for ivermectin, levamisole and morantel tartrate, but not thiabendazole. The concentration of levamisole giving 50% inhibition of migration (EC50) was determined for Cooperia curticei, Haemonchus contortus, Nematodirus spathiger, Ostertagia circumcincta, Trichostrongylus axei, T. colubriformis and T. vitrinus. EC50s differed between species but within species the EC50s for ensheathed and exsheathed L3 were similar except for N. spathiger which showed significantly higher EC50 for the ensheathed L3. No difference between EC50s for levamisole-resistant and susceptible strains of T. colubriformis were found. Similarly, morantel-resistant and susceptible strains of T. colubriformis could not be differentiated in this bioassay. The inhibition of L3 motility by known anthelmintic compounds in this bioassay suggests that the bioassay could be used as a screen for potential new anthelmintics.

The effect of age on the response of Romney sheep to gastrointestinal nematodes during grazing.

Three groups of Romney sheep, reared worm-free in pens from birth until 4, 16 or 28 months of age, were permitted to graze nematode-infected pasture for 4 weeks after which they were returned to pens and slaughtered 4 weeks later. Three groups of three Romney sheep reared and maintained worm-free for similar periods served as uninfected control groups. Faecal egg counts (FECs) 8 weeks after grazing commenced were significantly greater in 4-month-old sheep than the 28-month-old animals. At slaughter, no difference in nematode burdens among these three age groups was found. Histological examination of the abomasal and small intestine mucosa, taken from sheep at slaughter, revealed significantly greater numbers of globule leukocytes/mucosal mast cells (GL/MMC) bur fewer connective tissue type mast cells (CTMC) in sheep aged 16 and 28 months than in those aged 4 months. The numbers of eosinophils in the gastrointestinal mucosal tissues of the three groups of infected sheep were not significantly different. In uninfected sheep the numbers of eosinophils, GL/MMC and CTMC in the mucosal tissues did not differ between the three age groups and the numbers of GL/MMC and CTMC were similar to those in 4-month-old infected sheep. Eosinophil numbers in the mucosal tissue of the infected groups were significantly higher than in the uninfected groups. In the infected groups, FECs but not worm burdens were significantly negatively correlated with GL/MMC numbers.(ABSTRACT TRUNCATED AT 250 WORDS)