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Treatment of advanced head and neck cancer: multiple daily dose fractionated radiation therapy and sequential multimodal treatment approach.

Fifty-eight patients with advanced head and neck cancer were entered into a randomised trial comparing chemotherapy (DDP + bleomycin) alone, multiple daily fractionated radiation therapy, and multimodality therapy consisting of chemotherapy plus multiple fractionated radiation therapy. Multimodal therapy gave a significantly higher response rate (69%) than either single-treatment modality. The use of a multiple daily dose fractionation allowed radiation therapy to be completed over 10 treatment days, and the addition of chemotherapy to the radiation treatment did not significantly increase toxicity. Patients receiving multimodal therapy also survived significantly longer (median 50 weeks) than those receiving single-modality therapy (median 24 weeks).

Antineoplastic Combined Chemotherapy Protocols↗

Damage to the surface of the small intestinal villus: an objective scale of assessment of the effects of single and fractionated radiation doses.

Scanning electron microscopy has been used to compare damage to mouse small intestinal mucosa after irradiation with different doses of photons and neutrons. Various stages of the collapse of villous structure seen after radiation include the production of conical and rudimentary villi and a flattened mucosa. A scale is proposed to relate radiation to villous damage. Points from this scale are taken to produce comparative ratios for equivalent damage produced by different radiation conditions. RBE values are quoted for neutron. X and gamma radiation given as single or fractionated irradiation doses and as whole or partial body irradiation. The relationship between the stroma in intravillous pegs and that of the pericryptal compartment is explored.

Animals↗

The effect of misonidazole in combination with radiation dose fractionation.

Single doses or multiple fractions of 2, 3, 5 or 10 Gy were given daily to KHT Sarcomas, growing in C3H mice, in combination with a misonidazole dose of 0.5 mg/g body weight administered 30--40 min before each radiation dose. Cell survival assays were performed on groups of tumours after different total doses to determine tumour cell survival curves for each fractionation schedule. The results indicate that misonidazole is effective in sensitizing the tumours to single doses and to large dose fractions, but that the degree of sensitization declines with fraction size such that there is no difference between the survival curves obtained for 2 Gy fractions given with or without prior drug treatment. Comparison of iso-effect curves, derived from the data, with those for normal skin suggests that, even though misonidazole increases the effect of the radiation on the tumour when large dose fractions are used, the small dose fractions probably still give a better "therapeutic ratio".

Animals↗

Differential sensitivity of two predominant stromal progenitor cell subpopulations in bone marrow to single and fractionated radiation doses.

The sensitivity of fibroblastoid precursor cells in rat bone marrow to single and fractionated doses of gamma rays delivered in vivo was measured. In vitro colonies were classified as being compact or diffuse, and the progenitor cells for both types were slowly cycling in vivo (survival levels after exposure to hydroxyurea were 90 +/- 6% and 93 +/- 11%, respectively). The progenitor cells forming diffuse colonies were more resistant (D0 = 1.39 Gy) than those forming compact colonies (D0 = 0.76 Gy). The fractionation sensitivities were characterized by an alpha/beta ratio of 12.7 +/- 5.5 Gy for diffuse colonies and 4.5 +/- 3.0 Gy for compact colonies, respectively. The progenitor cells forming diffuse colonies may contribute more to long-term regeneration after high doses in vivo.

Animals↗

Effects of solar-simulated radiation dose fractionation on CD1a+ Langerhans cells and CD11b+ macrophages in human skin.

BACKGROUND: There are few human studies investigating the immunosuppressive effects of exposure to solar-simulated radiation (SSR) and its relationship with sunburn/erythema, and few comparative data on the importance of SSR exposure regimens. OBJECTIVES: To evaluate whether SSR-induced erythema is a reliable end-point for assessing damage to antigen-presenting cells (APCs) in human skin. METHODS: We compared the relationship between SSR-induced erythema and alterations in epidermal CD1a+ Langerhans cells (LCs) and CD11b+ macrophages in human volunteers after single exposures to 0, 0.5, 1, 2 or 3 minimal erythema doses (MED). We also investigated whether SSR exposure leads to an accumulation or accommodation of the same end-points by comparing the effects of a relatively low cumulative SSR dose (3 MED) given in varying daily dose fractions (4 x 0.75 MED, 2 x 1.5 MED and 1 x 3 MED). RESULTS: Single SSR exposures induced a dose-dependent increase in erythema. CD1a+ LCs remaining in the irradiated epidermis showed a dose-dependent increase in cell size and altered morphology. Significant depletion of CD1a+ LCs and presence of CD11b+ macrophages only occurred in sites irradiated with 2 MED and 3 MED. Dose fractionation had no effect on the final erythemal response but the 4 x 0.75 MED and 1 x 3 MED protocols were better tolerated than 2 x 1.5 MED for alterations in CD1a+ LC and CD11b+ cell numbers. In contrast, dose fractionation protected against alterations in CD1a+ LC morphology or cell size. CONCLUSIONS: We found that erythema is a poor indicator of alterations in epidermal APCs and that dose fractionation is an important parameter in the immunological effects of ultraviolet radiation.

Adult↗

Fractionated irradiation and haematopoiesis. I. The effect of a differently fractionated radiation dose of 600 R.

The effect of the same dose of irradiation (600 R) divided into two different fractions (500 + 100 R; 400 + 200 R; 300 + 300 R) upon the haematopoietic system of young rats (25 days old) was investigated. Free interval between the first and the second dose was 5 minutes. Changes were observed in bone-marrow, spleen and blood in all the experimental groups of 10 days after the irradiation. Spontaneous regeneration of haematopoiesis after a single dose of 600 R is higher than after division of this dose into two fractions, excluding the group where the dose was divided into two equal fractions. The most intensive haematopoietic repopulation was found in the group of rats irradiated with 300 + 300 R, where the primary dose was the smallest. In fractional conditions, the first dose is of primary importance for the repopulating capacity of the haematopoietic system regardless of the short free interval.

Animals↗

[Cellular composition of cerebral cortex in rat fetuses exposed to low-dose fractionated radiation].

Using histological and morphometric methods, the peculiarities of sensomotor cortex morphogenesis were studied in rat fetuses subjected to fractionated gamma-irradiation in the period from 6th to 18th prenatal days in doses of 5, 25, 50 and 25-75 cGy. It that an Exposure to a fractionated radiation was found to negatively affect stem cell proliferation in the developing cortex and to increase the intensity of cell destruction in proportion to the radiation dose. The absolute number of macroglial cells was increased in all the cellular zones of developing cortex, that could be the result of both reactive stimulation of their production due to functional insufficiency, and of accelerated transformation of radial gliocytes into macroglia. Irradiation with the doses of 5-75 cGy caused the deceleration of neuroblast migration into the primary cortex, as indicated by the reduction of cell number in neural differon in the neocortical anlage and cell number growth in deeper layers of the developing cortex.

Animals↗

Low-dose fractionated radiation as a chemopotentiator of neoadjuvant paclitaxel and carboplatin for locally advanced squamous cell carcinoma of the head and neck: results of a new treatment paradigm.

PURPOSE: Current therapies for locally advanced squamous cell carcinoma of the head and neck (SCCHN) result in 50% long-term remission. Low-dose radiotherapy (<100 cGy) induces enhanced cell killing in vitro via the hyper-radiation sensitivity phenomenon but has not been used in the clinical setting. On the basis of the demonstrated synergy between chemotherapy and low-dose fractionated RT, a novel neoadjuvant therapy was designed using low-dose fractionated RT as a chemopotentiator for locally advanced SCCHN. METHODS AND MATERIALS: Forty patients with locally advanced SCCHN received paclitaxel (225 mg/m2), carboplatin (area under the curve of 6), and four 80-cGy fractions of radiotherapy (two each on Days 1 and 2). This sequence was repeated on Days 22 and 23. RESULTS: Of the 40 patients enrolled, 39 were assessable. Grade 3 or worse toxicities included neutropenia (50%), infection (13%), arthralgias/myalgias (3%), skin (8%), lung (3%), and allergic reaction (3%), with no Grade 5 toxicity. The response was assessed radiographically and by panendoscopy. At the primary site, 11 patients (28%) had a complete response, 24 (62%) had a partial response, and 4 (10%) had stable disease. Of those with lymph node involvement, 10 (31%) had a complete response, 12 (38%) a partial response, 9 (28%) had stable disease, and 1 (3%) had progressive disease. The overall response rate was 82%. CONCLUSION: Low-dose fractionated RT combined with paclitaxel and carboplatin is effective in SCCHN and has a similar toxicity profile to chemotherapy alone. This novel approach provided a response rate of 90% at the primary site and a nodal response rate of 69%. Additional scientific investigation of this new treatment paradigm is warranted.

Adult↗

Stereotactic high dose fraction radiation therapy of extracranial tumors using an accelerator. Clinical experience of the first thirty-one patients.

A stereotactic body frame with a fixation device has been developed for stereotactic radiation therapy of extracranial targets, a precision localization and positioning system in analogy with the stereotactic head frames used for intracranial targets. Results of the first 42 treated tumors in 31 patients are presented. Most of the patients had solitary tumors in liver, lung or retroperitoneal space. Clinical target volumes ranged from 2 to 622 cm3 (mean 78 cm3) and minimum doses to the planning target volumes (PTV) of 7.7-30 Gy/fraction (mean 14.2 Gy) were given on 1-4 occasions to a total minimum dose to the PTVs of 7.7-45 Gy (mean 30.2 Gy) to the periphery of the PTV and total mean doses to the PTVs of 8-66 Gy (mean 41 Gy). The central part of the tumor was usually given about 50% higher dose compared to that of the periphery of the PTV by a planned inhomogeneous dose distribution. Some of the patients received stereotactic radiation therapy concomitantly to more than one target, in others new metastases were also treated which appeared during the follow-up period. We observed a local rate of no progressive disease of 80% during a follow-up period of 1.5-38 months. Fifty percent of the tumors decreased in size or disappeared.

Aged↗