Clinical gains have been reported from the use of nonstandard fractionation schedules planned with a radiobiological basis. Hyperfractionation provides the leading example, as described below, with accelerated fractionation being developed more recently. Although examples of almost every kind of fractionated schedule can be found in the literature over the past 90 years, it is only within the last decade that the biological factors concerning overall time and delayed proliferation after irradiation, and the effect of dose per fraction, have been understood. Both these factors operate differently on late- and early-reacting tissues, because cell proliferation in late-reacting tissues is slow or absent, but early reacting tissues and tumours depend upon cells that proliferate rapidly. This basic knowledge is still diffusing through the radiotherapy community and I hope this review will help the diffusion process. The biological factors concerning fractionation seem to apply to the majority of tissues and tu...

The linear-quadratic formula and progress in fractionated radiotherapy

Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of neoplastic lesions in the breast ducts. The goal for management of DCIS is to prevent the development of invasive breast cancer. This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.

https://www.unitypoint.org/desmoines/filesimages/Cancer%20Education/Oncology%20Nursing%20Conference/2015/2014%20NCCN%20Clin%20Pract%20Guidelines%20Male%20Sex%20Dysf.pdf

Clinical practice guidelines in oncology

In the adult male, a population of diploid stem-cell spermatogonia continuously undergoes self-renewal and produces progeny cells, which initiate the complex process of cellular differentiation that results in mature spermatozoa. We report here that stem cells isolated from testes of donor male mice will repopulate sterile testes when injected into seminiferous tubules. Donor cell spermatogenesis in recipient testes showed normal morpholigical characteristics and produced mature spermatozoa. This methodology, besides opening new avenues of basic research into spermatogenesis and stem-cell self-renewal, may prove useful as a tool for biomedical science and biotechnology.

https://www.pnas.org/content/pnas/91/24/11298.full.pdf

Spermatogenesis following male germ-cell transplantation

Purpose: To provide an analytical description of the effect of random and systematic geometrical deviations on the target dose in radiotherapy and to derive margin rules. Methods and Materials: The cumulative dose distribution delivered to the clinical target volume (CTV) is expressed analytically. Geometrical deviations are separated into treatment execution (random) and treatment preparation (systematic) variations. The analysis relates each possible preparation (systematic) error to the dose distribution over the CTV and allows computation of the probability distribution of, for instance, the minimum dose delivered to the CTV. Results: The probability distributions of the cumulative dose over a population of patients are called dose-population histograms in short. Large execution (random) variations lead to CTV underdosage for a large number of patients, while the same level of preparation (systematic) errors leads to a much larger underdosage for some of the patients. A single point on the histogram gives a simple "margin recipe." For example, to ensure a minimum dose to the CTV of 95% for 90% of the patients, a margin between CTV and planning target volume (PTV) is required of 2.5 times the total standard deviation (SD) of preparation (systematic) errors (Σ) plus 1.64 times the total SD of execution (random) errors (σ′) combined with the penumbra width, minus 1.64 times the SD describing the penumbra width (σ p ). For a σ p of 3.2 mm, this recipe can be simplified to 2.5 Σ + 0.7 σ′. Because this margin excludes rotational errors and shape deviations, it must be considered as a lower limit for safe radiotherapy. Conclusion: Dose-population histograms provide insight into the effects of geometrical deviations on a population of patients. Using a dose-probability based approach, simple algorithms for choosing margins were derived.

The probability of correct target dosage: dose-population histograms for deriving treatment margins in radiotherapy

Background Radiotherapy is often the primary treatment for advanced head and neck cancer, but the rates of locoregional recurrence are high and survival is poor. We investigated whether hyperfractionated irradiation plus concurrent chemotherapy (combined treatment) is superior to hyperfractionated irradiation alone. Methods Patients with advanced head and neck cancer who were treated only with hyperfractionated irradiation received 125 cGy twice daily, for a total of 7500 cGy. Patients in the combined-treatment group received 125 cGy twice daily, for a total of 7000 cGy, and five days of treatment with 12 mg of cisplatin per square meter of body-surface area per day and 600 mg of fluorouracil per square meter per day during weeks 1 and 6 of irradiation. Two cycles of cisplatin and fluorouracil were given to most patients after the completion of radiotherapy. Results Of 122 patients who underwent randomization, 116 were included in the analysis. Most patients in both treatment groups had unresectable disea...

https://www.nejm.org/doi/pdf/10.1056/NEJM199806183382503

Hyperfractionated Irradiation with or without Concurrent Chemotherapy for Locally Advanced Head and Neck Cancer

When analysis of results of radiotherapy for nearly 500 patients with oropharyngeal cancer showed evidence for rapid tumor regrowth during extensions of treatment from about 5 weeks to about 8 week...

https://www.tandfonline.com/doi/pdf/10.3109/02841868809090333

The hazard of accelerated tumor clonogen repopulation during radiotherapy.

Mouse testes were studied histologically 35 or 42 days after irradiation. When doses greater than about 800 rads of gamma -rays are given, regeneration of spermatogenic epithelium occurs in discrete foci. It is assumed that a single surviving spermatogenic stem cell can regenerate a spermatogenic focus, and that the absence of spermatogenesis in a tubule signifies the absence of a surviving stem cell in that region of the tubule. The fraction of tubules containing spermatogenic colonies was used as an assay of stem-cell survival. The mean D/ sub o/ value of the singledose survival curve was 180 rads. Survivors of a first dose of 600 rads repair sublethal damage during the first few hours after irradiation. The amount of recovery measured in splitdose studies using intervals of 24 hr to 14 days is less than that measured 4 hr after exposure. This is interpreted as evidence for the existence of phases in the division cycle in which the stem cells are sensitive to radiation and into which a proportion of the first-dose survivors progress. Although surviving stem cells progress through the division cycle, and eventually form a focus of spermatogenesis, regeneration of stem cell numbers was not found in experimentsmore » continuing for 14 days after irradiation. The relevance of these characteristics to the development of fractionated-dose radiotherapy is discussed.« less

Radiation survival and regeneration characteristics of spermatogenic stem cells of mouse testis.

The chance of life-threatening complications occurring late after brain irradiation limits the efficacy of this form of cancer therapy. The molecular and cellular events that trigger radiation-induced brain damage are still unknown, but since they have the potential to serve as valuable targets for therapeutic intervention they are worth delineating. In this murine study, the effect of irradiation on the expression of molecules which are known to contribute to brain damage in other model systems was examined. Expression of genes encoding cytokines (TNF alpha / beta, IL-1 alpha / beta, IL-2, IL-3, IL-4, IL-5, IL-6 and IFN- gamma) , cytokine receptors (TNF-Rp55 and p75, IL-1R- p60 and p80, IFN- gamma R, and IL-6R), the cell adhesion molecule (ICAM-1), inducible nitric oxide synthetase (iNOS), anti-chymotrypsin (EB22/5.3), and the gliotic marker (GFAP) was evaluated over a 6-month period using a sensitive RNase protection assay (RPA). We had previously demonstrated that within 24 h of brain irradiation there...

H. R. Withers

Papers

The hazard of accelerated tumor clonogen repopulation during radiotherapy.

Radiation survival and regeneration characteristics of spermatogenic stem cells of mouse testis.

Delayed molecular responses to brain irradiation

Dose-time considerations of head and neck squamous cell carcinomas treated with irradiation.

Alpha/beta value and the importance of size of dose per fraction for late complications in the supraglottic larynx