Many difficulties are inherent to pharmacoeconomic studies. Because these studies are observational, there are many factors that cannot be controlled; for example, there are many variations across the country in the practice of any particular therapy. Therefore, designing a case report form that will match the source documents from various investigator sites is not easy. Issues arise in every activity such as choice of investigator site, data collection, data analysis, and interpretation of the results. These issues will be discussed, and an example of a pharmacoeconomic study conducted to evaluate the cost-effectiveness of patch testing in patients diagnosed with allergic contact dermatitis will be presented.

Clinical Trials as Topic↗

PubMedDate not supplied

High-dose-rate brachytherapy at 14 Gy per hour to point A: preliminary results of a prospectively designed schedule for cancer of the cervix based on the linear-quadratic model.

The objective of this study was to describe the results and complications of a prospectively designed high-dose-rate (HDR) brachytherapy schedule for early-stage cancer of the cervix, at 14 Gy/h to point A, based on the linear-quadratic model and our clinical experience. We used a combination of brachytherapy and external beam pelvic and parametrial irradiation in 88 consecutively seen patients with stage IB1-IIB treated by irradiation alone (1995-1998). The modeled HDR schedule consisted of three insertions on three treatment days separated by 10 days, with six 7 Gy planned brachytherapy fractions to point A, at 14 Gy/h, two on each treatment day with an interfraction interval of 6 h, plus an 18 Gy external whole-pelvic dose followed by additional parametrial irradiation. The calculated biologically effective dose (BED) was 92 Gy10 for tumor and 110 Gy3 for the rectum, equivalent to 77 and 66 Gy in 2 Gy fractions, respectively. The median overall treatment time was 41 days. The actuarial 4-year central recurrence-free rate, pelvic control, and disease-free survival rate were 97%, 93%, and 88% for stages IB-IIA and 79%, 75%, and 75% for stage IIB. The actuarial 4-year late complication rate for grades 2-3 was 4.7% (scale 0-3). We conclude that preliminary results of this HDR brachytherapy schedule for early-stage disease at a median follow-up of 52 months are as effective as the previously used low dose rate (LDR) at 0.44 Gy/h at point A. They are also as effective as medium-dose-rate schedules (MDR) at 1.6-1.5 Gy/h at this institution and do not require a further increase in fractionation of intracavitary treatments or in the whole-pelvic external beam irradiation dose common to standard HDR schedules. In addition, more patients per machine can be treated per day compared with MDR. Longer follow-up is required for a complete assessment of late complications.

Adenocarcinoma↗

PubMedDate not supplied

Developing aspects of radiation oncology.

Both physics and radiobiology provide growing points in modern radiotherapy. Better physical dose distributions appear to be still worth achieving and can be obtained from beams of protons, heavy ions, or negative pi mesons because a peak region of high dose is deposited at depth in tissue. The heavier ion and pions also have biological properties of high LET radiation which could be important: the radioresistance of hypoxic cells in tumors is less, and tissues which are proliferating fast may be relatively more vulnerable. Although fast neutrons provide ordinary physical dose distributions, their high LET properties are similar to those of ions as heavy as neon. Drugs which specifically radiosensitize hypoxic cells offer a way of determining with certainty how important hypoxic cells are in radiotherapy. Hyperthermia is in its early stages but promises to damage just those cells poor in nutrients which are relatively resistant to ionizing radiation. Radioprotecting drugs, which depend upon poor uptake in tumors but high uptake in normal tissues, are also being tested.

Cell Survival↗

PubMedDate not supplied

Radiobiology of radiolabeled antibody therapy as applied to tumor dosimetry.

This paper reviews the radiobiological aspects of radioimmunotherapy (RIT) with radiolabeled antibodies, including comparisons between RIT and external beam irradiation. The effectiveness of cell killing by radiation decreases with the dose rate and the rate of decrease is determined by the size of the shoulder on the radiation survival curve. Tumors with poor repair capabilities exhibit less of a dose rate effect than tumors with good repair capabilities. Continued tumor cell proliferation during treatment occurs at very low dose rates and can contribute to the reduced effectiveness of low dose rate radiation. Toxicity to normal tissues will determine the total dose of radiolabeled antibody that can be given and this will be influenced by the choice of both the radionuclide and the antibody. The reported enhanced effectiveness of RIT may be due to multiple factors including selective targeting of cells responsible for tumor volume doubling, tumor surface binding rather than homogeneous binding throughout the tumor volume, targeting of the tumor vasculature, or block of cell cycle progression in G2. During RIT, there is less time for reoxygenation of hypoxic tumor cells than during a course of conventional external beam radiotherapy. It has not yet been determined whether this will have a detrimental effect on RIT. Probably the most important factor in the success of RIT is dose heterogeneity. Any viable portion of a tumor that is not targeted and does not receive a significant radiation dose will potentially lead to treatment failure, no matter how high the dose received by the remainder of the tumor. Comparisons between RIT and external beam radiation have shown a wide range of relative efficacy. Tumors most likely to respond to RIT are tumors with poor repair capabilities, tumors that are susceptible to blockage in radiosensitive phases of the cell cycle, tumors that reoxygenate rapidly, and tumors that express the relevant antigen homogeneously. From a radiobiological perspective, it appears that RIT alone is unlikely to cure many tumors and that combination with other treatment modalities will be essential.

Cell Hypoxia↗

PubMedDate not supplied

[Relation of dosage-time in radiotherapy].

Explore the source record for details and available documents.

Animals↗