Bioeffect modeling and equieffective dose concepts in radiation oncology--terminology, quantities and units.

The International Commission on Radiation Units and Measurements (ICRU) Report Committee on "Bioeffect Modeling and Biologically Equivalent Dose Concepts in Radiation Therapy" is currently developing a comprehensive and consistent framework for radiobiological effect modeling based on the equieffective dose, EQDX(α/ß), a concept encompassing BED and EQD2 as special cases.

Merged imaging and expanded target selection in gamma knife radiosurgical ablation of the sphenopalatine ganglion.

Sphenopalatine neuralgia, or Sluder's neuralgia, refers to a consistent clustering of clinical symptoms: intermittent episodes of vasomotor hyperactivity causing conjuctival injection, lacrimation, serous nasal discharge and unilateral nasal mucosal inflammation, sensory disturbances of the palate and oropharynx with distorted gustatory sensations, and lancing, unilateral pain most often located in the area of the inferomedial orbit and nasal base or at the region of the mastoid process. This particular clinical entity has also proven difficult to manage effectively, especially when not clearly secondary to other medical conditions such as paranasal sinus infection or bony nasal deformities. This condition has been treated with success using Gamma Knife radiosurgery in at least 1 other case reported in the literature. We present a second patient whose sphenopalatine neuralgia was treated successfully with stereotactic radiosurgery and discuss the possibilities of this modality as an option for patients with a refractory condition.

p16 gene alterations in locally advanced squamous cell carcinoma of the head and neck.

We previously documented the presence of mutations/deletions in the tumor suppressor gene p16 in squamous cell carcinoma of the head and neck (SCCHN). However, the association of these p16 alterations with clinical outcome is unknown. In this study, RNA was isolated from 19 frozen SCCHN from 19 patients who were previously enrolled in the OSU intensification regimen 2. Quantitative real-time RT-PCR and direct sequencing analysis was then performed on the specimens to detect p16 gene alterations. Clinical outcome for each patient was updated and correlated with the p16 alterations found. Five tumor specimens were found to have no or very low expression of p16 when compared with normal tissue. The remaining 14 tumor samples demonstrated overexpression of p16 relative to the level of expression in normal tissue. Sequence analysis of the p16 RT-PCR product from these specimens allowed identification of mutational changes in the coding sequence of p16 in four of the SCCHN specimens. Subsequent analysis of clinical outcome associated with locoregional/distant failure demonstrated no correlation with either altered expression of p16 or mutational status of p16. Results from this study indicate that p16 alterations are frequently found in this cohort of SCCHN. However, p16 alterations alone do not appear to be associated with clinical outcome.

Gamma Knife radiosurgery for intracranial metastatic melanoma: an analysis of survival and prognostic factors.

Objective of this study was to evaluate retrospectively the effectiveness of Gamma Knife radiosurgery for intracranial metastatic melanoma and to identify prognostic factors related to survival. Twenty-six patients with intracranial metastases (72 lesions) from melanoma underwent Gamma Knife radiosurgery. In 14 patients (54%) whole-brain radiotherapy (WBRT) was performed as part of the initial treatment, and in 12 patients (38%) immunotherapy and/or chemotherapy was given after Gamma Knife radiosurgery. The median tumor volume for Gamma Knife radiosurgery treated lesions was 1.72 cm3. The median prescribed radiation dose was 18 Gy (range 8-22 Gy) typically prescribed to the isodose at the tumor margin. Univariate and multivariate analyses were used to determine significant prognostic factors affecting survival. Overall median survival was 6 months after Gamma Knife radiosurgery, and 1-year survival was 25%. The median survival from the onset of brain metastases was 9 months and from the original diagnosis of melanoma was 50 months (range 4-160 months). There were no major acute or late GKS complications. In univariate testing, the Karnofsky score equal to or higher than 90% (P < 0.01, log-rank test), supratentorial localization (P < 0.001, log-rank test), intracranial tumor volume less than 1 cm3 (P < 0.02, log-rank test), and absence of neurological signs or symptoms before Gamma Knife radiosurgery (P < 0.003, log-rank test) were significant favorable factors for survival. In multivariate regression analyses, the most important predictors associated with increased survival were a KPS > or = 90 (P < 0.023), female sex (P < 0.004), supratentorial localization (P < 0.01), and absence of neurological symptoms (P < 0.008). Radiosurgery is a noninvasive, safe, and effective treatment option for patients with single or multiple intracranial metastases from melanoma. Female sex, Karnofsky score > or = 90, supratentorial localization and lack of symptoms before the Gamma Knife radiosurgery were good independent predictors of survival.

Radiobiological rationale and patient selection for high-LET radiation in cancer therapy.

The rationale for introducing ion beams in cancer therapy is the high level of physical selectivity that can be achieved with ions, equal or even better than with proton beams or modern photon techniques, as well as the potential advantage of high-LET radiations for some tumour types and sites. The radiobiological arguments for high-LET radiation in cancer therapy are reviewed: reduction of OER in the case of hypoxic and poorly-reoxygenating tumours, and the lesser importance of repair phenomena which are a problem in controlling repair-proficient photon-resistant tumours. Fast neutrons were the first type of high-LET radiation used clinically, and were often applied under suboptimal technical conditions. Nevertheless, useful clinical information was derived from the neutron experience. A greater benefit from neutrons than from conventional radiotherapy was found for several tumour sites. The present discussion is limited to the results for salivary gland tumours and prostatic adenocarcinoma. Based on the fast neutron experience, radiobiological arguments, and the added benefit of excellent physical selectivity of ion beams, the potential clinical indications for high-LET ions are discussed: hypoxic, slowly growing and well-differentiated photon-resistant tumours. One of the main remaining issues is the selection of individual patients for high- or low-LET radiation. Since the physical selectivity of ions now matches that obtained with other techniques, the selection of patients will be based only on the radiobiological characteristics of the tumour.

Pain in the foot: calcaneal metastasis as the presenting feature of endometrial cancer.

BACKGROUND: Ninety percent of endometrial cancer cases present with abnormal bleeding. Bone metastasis as the presenting feature is extremely rare. CASE: A 76-year-old woman presented with right heel pain. She had no vaginal bleeding or other symptoms suggestive of endometrial cancer. After failure of conservative therapy, imaging studies demonstrated a calcaneal metastasis. A biopsy showed adenocarcinoma. She received local radiation to her foot, with complete resolution of symptoms. Subsequent computed tomography scans showed multiple pulmonary nodules, pelvic and inguinal lymphadenopathy, and an enlarged uterus. Endometrial biopsy confirmed endometrial adenocarcinoma. She received palliative therapy and died 11 months after the diagnosis was made on the endometrial biopsy. CONCLUSION: This case highlights the rare presentation of endometrial cancer with foot pain secondary to calcaneal metastasis. Aggressive treatment of bone metastases can provide effective palliation of symptoms.