In vivo cell kinetic measurements in a randomized trial of continuous hyperfractionated accelerated radiotherapy with or without mitomycin C in head-and-neck cancer.

Purpose: Tumor cell repopulation is still considered to be a major cause of failure in radiotherapy. In this study, we investigated the influence of cell kinetic parameters on the outcome of patients treated in a randomized trial of accelerated fractionation, with or without mitomycin C, vs. conventional fractionation.

Continuous hyperfractionated accelerated radiotherapy with/without mitomycin C in head and neck cancer.

Purpose: To evaluate the effect of mitomycin C to an accelerated hyperfractionated radiation therapy. The aim was to test a very short schedule with/without mitomycin C (MMC) with conventional fractionation in histologically verified squamous cell carcinoma of the head and neck region.

Methods And Materials: From October 1990 to December 1996, 188 patients entered the trial.

Conventional vs accelerated fractionation in head and neck cancer.

From October 1990 to March 1994, 90 patients entered a prospectively randomised trial in head and neck cancer. All patients had verified squamous cell carcinoma and were referred for primary radiation therapy. Tumours originated in the oral cavity in 25, oropharynx in 37, larynx in 15 and hypopharynx in 13 cases.

Selective cellular acidification and toxicity of weak organic acids in an acidic microenvironment.

The mean extracellular pH (pHe) within solid tumours has been found to be lower than in normal tissues. Agents which cause intracellular acidification at low pHe might have selective toxicity towards cells in tumours. Weak acids (or their anions) with pKa values in the range of 4-6 have a higher proportion of molecules in the uncharged form at low pHe and can diffuse more rapidly into cells.

[Atypical fractionation in advanced squamous-cell carcinomas of the head-neck area].

From May 1990 to May 1991, 23 patients with advanced, inoperable squamous cell cancers, clinically staged as III or IV, were treated by unconventional fractionation radiotherapy. Treatment consisted of a continuous hyperfractionated accelerated radiotherapy, delivering a total dose of 55.3 Gy within 17 consecutive days.

Use of a high frequency ultrasound microscope to image the action of 2-nitroimidazoles in multicellular spheroids.

A system was designed to allow imaging of control and drug treated multicellular spheroids with a high frequency backscatter ultrasound microscope. It allowed imaging of individual spheroids under good growth conditions. Since little data were available on cellular toxicity of ultrasound at these high frequencies (80 MHz), studies were undertaken to evaluate effects on cell survival, using a colony forming assay.

Mode of interaction of 5-fluorouracil, radiation, and mitomycin C: in vitro studies.

An examination of the effects of radiation combined with either 5-fluorouracil, Mitomycin C, or both drugs in vitro has been made using a mouse squamous tumor cell line SCC VIITo and cell viability as an endpoint. Depending on how the survival endpoint was calculated, the interaction of 5-fluorouracil, Mitomycin C, or 5-fluorouracil plus Mitomycin C with radiation was greater than additive (plating efficiency) or only additive (viable cells per flask). These results suggest that the cytostatic effect of these drugs may be an important aspect of their action clinically.

The potential of lactate and succinate to kill nutrient deprived tumor cells by intracellular acidification.

We have investigated the ability of the weak acids, lactate, succinate, and the monomethylester of succinate, to cause intracellular acidification of EMT-6 and MGH-U1 cells. Each of the three substances caused a decrease of intracellular pH (pHi) when the cell lines were exposed at low extracellular pH (pHe) in the range 6.0-6.

Combined modality treatment of advanced cancers of the oral cavity and oropharynx.

From May 1985 to June 1988, 70 evaluable patients with advanced squamous cell cancers of the oral cavity and the oropharynx were treated with preoperative combined radio-chemotherapy. Treatment consisted of 50 Gy/25 fractions/5 weeks, combined with concomitant administration of mitomycin C on day 1 (15 mg/m2, i.v.

Response to preoperative concomitant radiochemotherapy with mitomycin C and 5-fluorouracil in advanced head and neck cancer.

Advanced head and neck tumours have a poor prognosis due to the high frequency of local recurrence. Multimodality treatment has been shown to be effective in decreasing local recurrence. In this study, 51 patients with advanced oral and oropharyngeal carcinoma were entered in a trial of preoperative radio-chemotherapy.

Histologic tumor regression grades in squamous cell carcinoma of the head and neck after preoperative radiochemotherapy.

Forty-one patients with Stage III and IV squamous cell carcinomas (SCC) of the head and neck were treated preoperatively with mitomycin C and 5-fluorouracil and concomitant radiotherapy. Operation specimen were examined histologically, the percentage of vital tumor cells and devitalized tumor cells were graduated. The grade of regression was classified according to a four-stage scale.

[Cloning of solid tumors in double agar (human tumor stem cell assay].

62 specimens from 37 patients with solid malignant tumours were cloned by the human tumour stem cell assay (HTSCA). The growth rate, the use of two different disaggregation methods and their influence on vitality and plating efficiency were analyzed as well as the cloning rate from different tumour regions and metastases. The growth rate was 68%, and there was a significant difference in the vitality, depending on which mode of disaggregation was used.

[Radiotherapy of choroid metastases in breast carcinoma].

From 1975 to 1984, thirteen patients were submitted to radiotherapy for choroid metastases of mammary carcinoma. Bilateral manifestation was found in three cases, thus sixteen eyes have been treated. All irradiations were performed with high voltage equipment.

[Preoperative radiochemotherapy in advanced oral and oropharyngeal carcinoma].

In a prospective study, 16 patients with advanced carcinoma of oral cavity and oropharynx were submitted to a combined preoperative radio-chemotherapy. The radiosensitizers mitomycin and 5 fluorouracil were given simultaneously with the beginning of radio-therapy. The primary tumor as well as the lymph node regions were exposed to a total dose of 50 Gy administered over five weeks.