Is sensitization with nicotinamide and carbogen dependent on nicotinamide concentration at the time of irradiation?

Purpose: To determine whether tumour radiosensitization and the therapeutic benefit of administering carbogen with nicotinamide depend upon irradiating at the time of peak drug concentration.

Materials And Methods: Local tumour control of CaNT tumours in CBA mice and acute skin reactions in albino WHT mice were assessed after treatment with 10 X-ray fractions in air, carbogen alone or combined with 0.1, 0.

Swedish Cancer Society radiation therapy research investigation.

In an investigation by the Swedish Cancer Society, the present status, critical issues and future aspects and prospects were described by an expert group for each of nine major areas of radiation research. A summary of the investigation is presented in this report. A more extensive summary (in Swedish) can be found at www.

Theoretical simulation of oxygen tension measurement in the tissue using a microelectrode: II. Simulated measurements in tissues.

Background And Purpose: The objectives of this study were to make a computer simulation of tissues with different vascular structures and to simulate measurements of oxygen tension using an Eppendorf-like electrode in these tissues and to compare the response to radiation of the tissues with the real oxygen distributions (called input distribution) with the response to radiation of the tissues in which the oxygen distribution is given by the results of the simulated measurements (called output distribution).

Materials And Methods: The structure of various tissues and the measurements of oxygen tension using a microelectrode were simulated using a computer program. The mathematical model used combines the description of a gradient of tissue oxygenation and the electrode absorption process.

Vascular architecture, hypoxia, and proliferation in first-generation xenografts of human head-and-neck squamous cell carcinomas.

Purpose: To quantify the physiologic status of human tumor cells in relation to the tumor vasculature.

Methods And Materials: Fourteen tumors of 11 first-generation xenograft lines of human head-and-neck squamous cell carcinoma were injected with the hypoxic cell marker pimonidazole, the proliferation marker BrdUrd, and the perfusion marker Hoechst 33342. Consecutive tissue sections were processed with immunohistochemical methods and analyzed with image-analysis techniques.

Dose response and latency for radiation-induced fibrosis, edema, and neuropathy in breast cancer patients.

Purpose: To study the incidence of various forms of late normal tissue injuries to determine the latency and dose-response relationships.

Methods: We retrospectively analyzed the clinical records of 150 breast cancer patients treated with radiotherapy after mastectomy in the mid to late 1960s. None of the patients had received chemotherapy as a part of their primary treatment.

Theoretical simulation of oxygen tension measurement in tissues using a microelectrode: I. The response function of the electrode.

The aim of this article is to determine the correlation between the actual oxygen distribution in tissues and the distribution of oxygen measured by microelectrodes. This correlation is determined by the response function of the electrode, which depends on the oxygen consumed by the electrode. In tissue it is necessary to consider the gradients resulting from cellular respiration.

Swedish Cancer Society Radiation Therapy Research Investigation.

In an investigation by the Swedish Cancer Society, the present status, critical issues and future aspects and prospects were described by an expert group for each of nine major areas of radiation research. A summary of the investigation is presented in this report. A more extensive summary (in Swedish) can be found at www.

Left sided vocal cord paralysis: a newly recognized late complication of mediastinal irradiation.

Background And Purpose: To evaluate the incidence of vocal cord paralysis in a group of breast cancer patients treated with post operative radiation therapy after radical mastectomy.

Materials And Methods: A group of 150 patients operated with total mastectomy and axillary clearance received, in 1963-1965, post-operative radiotherapy to the parasternal, axillary and supraclavicular lymph node regions. The cohort has now been followed up to 34 years.

Changes in tumor hypoxia measured with a double hypoxic marker technique.

Purpose: Development of a double hypoxic cell marker assay, using the bioreductive nitroimidazole derivatives CCI-103F and pimonidazole, to study changes in tumor hypoxia after treatments that modify tumor oxygenation.

Methods And Materials: Both hypoxic markers were visualized by immunohistochemical techniques to detect changes in hypoxic fraction induced by carbogen breathing (95% O(2) and 5% CO(2)) or hydralazine injection. The protocol was tested in a human laryngeal squamous cell carcinoma xenograft line.

Timescale of evolution of late radiation injury after postoperative radiotherapy of breast cancer patients.

Purpose: To evaluate the incidence and prevalence of various signs of late morbidity, their time of appearance and pattern of progression during an observation period up to 34 years in breast cancer patients treated with postoperative radiation therapy after radical mastectomy.

Methods And Materials: A group of 71 breast cancer patients received in 1963-1965 aggressive postoperative telecobalt therapy to the parasternal, axillary, and supraclavicular lymph node regions after total mastectomy and axillary clearance. None of the patients received chemotherapy either prior to, or after the irradiation as part of their primary treatment.

Brachial plexopathy after postoperative radiotherapy of breast cancer patients--a long-term follow-up.

In 1963-1965 a group of 71 patients operated on for breast cancer with total mastectomy and axillary clearance were given aggressive postoperative telecobalt therapy to the axillary, supraclavicular and parasternal lymph node regions. The prescribed dose to these lymph node regions was 44 Gy in 11 fractions. Only two of the three fields were treated per day.

ARCON: accelerated radiotherapy with carbogen and nicotinamide in head and neck squamous cell carcinomas. The experience of the Co-operative group of radiotherapy of the european organization for research and treatment of cancer (EORTC).

Background: Since there is increasing evidence that both acute (perfusion-limited) and chronic (diffusion-limited) hypoxia, and tumor repopulation may prejudice the outcome of radiotherapy, the combination of carbogen (95% oxygen-5% carbon dioxide) and nicotinamide with accelerated radiotherapy (ARCON) should reduce the impact of these factors of radioresistance.

Aim: This clinical study was aimed at determining the feasibility, as well as the qualitative and quantitative toxic effects of a therapeutic approach based on ARCON, and assessing the tumor response rates that can be achieved with this regime in patients with locally advanced tumors of the head and neck.

Methods: A phase I/II study conducted between 1993 and 1996 by the Co-operative Group of Radiotherapy of the EORTC included three consecutive steps: accelerated fractionation (AF) combined with carbogen (11 analyzable patients), AF combined with the daily administration of nicotinamide (n=10), and AF with both carbogen and nicotinamide (n=17).

Inducible repair and intrinsic radiosensitivity: a complex but predictable relationship?

Two groups have proposed a simple linear relationship between inducible radioresistance in a variety of mammalian cells and their intrinsic radiosensitivity at 2 Gy (Lambin et al., Int.J.

Perivascular cell protection in vivo and increased cell survival in vitro by the antihypertensive agent carvedilol following radiation.

Carvedilol, an antihypertensive drug with activity on adrenoceptors as well as on calcium channel activity, has recently been introduced. In the present study we investigated whether carvedilol interacts with the cytotoxicity induced by irradiation in vitro as well as in vivo. A daily injection of carvedilol in clinically relevant concentrations (3 mg/kg subcutaneously), 4 days before and 3 days after a single radiation dose of 20 Gy significantly decreased the inflammatory reaction in the rat lung, evaluated as number of inflammatory cells in the perivascular area.

Inducible repair and the two forms of tumour hypoxia--time for a paradigm shift.

Clinical experience shows that there is a therapeutic window between 60 and 70 Gy where many tumours are eradicated, but the function of the adjacent normal tissues is preserved. This implies much more cell kill in the tumour than is acceptable in the normal tissue. An SF2 of 0.

ARCON: accelerated radiotherapy with carbogen and nicotinamide in non small cell lung cancer: a phase I/II study by the EORTC.

Background: Non small cell lung cancers (NSCLC) are rapidly proliferating tumours, which are characterized by the presence of extensive hypoxic components, especially in patients with advanced loco-regional disease. Previous studies suggest a deleterious impact of acute (perfusion-limited) hypoxia on the outcome of radiotherapy for these tumours.

Aim: This pilot study was aimed at determining the feasibility and tumour response rates that can be achieved with an ARCON regime in patients with locally advanced, staged IIIA or B, NSCLC tumours.

The ribonucleoside diphosphate reductase inhibitor (E)-2'-deoxy-(fluoromethylene)cytidine as a cytotoxic radiosensitizer in vitro.

(E)-2'-Deoxy-(fluoromethylene)cytidine (FMdC) is known as an inhibitor of ribonucleoside diphosphate reductase, a key enzyme in the de novo pathway of DNA synthesis. FMdC was tested as a modifier of radiation response in vitro on a human colon carcinoma cell line (WiDr), and the observed radiosensitization was confirmed on two human cervix cancer cell lines (C33-A and SiHa). Using the clonogenic assay, the effect ratio (ER) at a clinically relevant dose level of 2 Gy was 2.

Accelerated radiotherapy, carbogen, and nicotinamide in glioblastoma multiforme: report of European Organization for Research and Treatment of Cancer trial 22933.

Purpose: A three-step phase I/II trial associating accelerated radiotherapy with carbogen (step 1, ARCO), with nicotinamide (step 2, ARN), or with both (step 3, ARCON) was conducted, the aim of which was to overcome the effects of proliferation and hypoxia as potential causes of tumor radioresistance in glioblastoma multiforme.

Patients And Methods: Radiotherapy consisted of 60 Gy delivered over 4 weeks in 1.5-Gy fractions twice daily, 5 days a week.

Labelling indices in human tumours: to apply corrections or not--that is the question.

The advent of halogenated pyrimidines (bromodeoxyuridine, BrdU; idoxuridine, IdU) and antibodies to recognize them has opened new horizons for the measurement of proliferation in human tumours. These precursors of DNA can be given to patients and a single biopsy can be taken to measure in a flow cytometer both the fraction of labelled cells and their rate of movement through the S phase. From these two parameters the potential doubling time, T(POT), can be calculated.