Preplanning prediction of the left anterior descending artery maximum dose based on patient, dosimetric, and treatment planning parameters.

Purpose: Maximum dose to the left anterior descending artery (LADmax) is an important physical constraint to reduce the risk of cardiovascular toxicity. We generated a simple algorithm to guide the positioning of the tangent fields to reliably maintain LADmax <10 Gy.

Methods And Materials: Dosimetric plans from 146 consecutive women treated prone to the left breast enrolled in prospective protocols of accelerated whole breast radiation therapy, with a concomitant daily boost to the tumor bed (40.

Use of a Flexible Inflatable Multi-Channel Applicator for Vaginal Brachytherapy in the Management of Gynecologic Cancer.

Introduction: Evaluate use of novel multi-channel applicator (MC) Capri™ to improve vaginal disease coverage achievable by single-channel applicator (SC) and comparable to Syed plan simulation.

Materials And Methods: Twenty-eight plans were evaluated from four patients with primary or recurrent gynecologic cancer in the vagina. Each received whole pelvis radiation, followed by three weekly treatments using HDR brachytherapy with a 13-channel MC.

A phase 2 trial of stereotactic radiosurgery boost after surgical resection for brain metastases.

Purpose: To evaluate local control after surgical resection and postoperative stereotactic radiosurgery (SRS) for brain metastases.

Methods And Materials: A total of 49 patients (50 lesions) were enrolled and available for analysis. Eligibility criteria included histologically confirmed malignancy with 1 or 2 intraparenchymal brain metastases, age≥18 years, and Karnofsky performance status (KPS)≥70.

Comparison of Acute and Late Toxicity of Two Regimens of 3- and 5-Week Concomitant Boost Prone IMRT to Standard 6-Week Breast Radiotherapy.

Purpose: Limited information is available comparing toxicity of accelerated radiotherapy (RT) to that of standard fractionation RT for early stage breast cancer. We report early and late toxicities of two prone regimens of accelerated intensity-modulated radiation therapy (IMRT) with a concomitant boost (CB) to the tumor bed delivered over 3 or 5 weeks as compared to standard 6 week RT with a sequential electron boost.

Methods: From 2/2003 to 12/2007, 169 consecutive patients with Stage I-II breast cancer were offered the choice to undergo prone RT with either: a 6-week standard RT regimen of 46 Gy/23 fractions (fx) to the whole breast (WB), followed by a14 Gy sequential boost (SB) to the tumor bed (6wSB), a 5-week regimen of 50 Gy to WB with an IMRT CB of 6.

Prospective assessment of optimal individual position (prone versus supine) for breast radiotherapy: volumetric and dosimetric correlations in 100 patients.

Purpose: Damage to heart and lung from breast radiotherapy is associated with increased cardiovascular mortality and lung cancer development. We conducted a prospective study to evaluate which position is best to spare lung and heart from radiotherapy exposure.

Methods And Materials: One hundred consecutive Stage 0-IIA breast cancer patients consented to participate in a research trial that required two computed tomography simulation scans for planning both supine and prone positions.

Radiation sensitivity of GL261 murine glioma model and enhanced radiation response by flavopiridol.

Response of a solid tumor to radiation treatment depends, in part, on the intrinsic radiosensitivity of tumor cells, the proliferation rate of tumor cells between radiation treatments and the hypoxic state of the tumor cells. A successful radiosensitizing agent would target S-phase cells and hypoxia. Recently, we demonstrated the anti-tumor effects of flavopiridol in the GL261 murine glioma model might involve 1) recruitment of tumor cells to S-phase (Newcomb et al Cell Cycle 2004; 3:230-234) and 2) an anti-angiogenic effect on the tumor vasculature by downregulation of hypoxia-inducible factor -1alpha (HIF-1alpha) (Newcomb et al Neuro-Oncology 2005; 7:225-235).

Biologic comparison of partial breast irradiation protocols.

Purpose: To analyze the dose/fractionation schedules currently used in ongoing clinical trials of partial breast irradiation (PBI) by comparing their biologically effective dose (BED) values to those of three standard whole breast protocols commonly used after segmental mastectomy in the treatment of breast cancer.

Methods And Materials: The BED equation derived from the linear-quadratic model for radiation-induced cell killing was used to calculate the BEDs for three commonly used whole breast radiotherapy regimens, in addition to a variety of external beam radiotherapy, as well as high-dose-rate and low-dose-rate brachytherapy, PBI protocols.

Results: The BED values of most PBI protocols resulted in tumor control BEDs roughly equivalent to a 50-Gy standard treatment, but consistently lower than the BEDs for regimens in which the tumor bed receives a total dose of either 60 Gy or 66 Gy.

Pharmacogenomics and breast cancer.

Germline variants can be used to study breast cancer susceptibility as well as the variable response to both drug and radiation therapy used in the treatment of breast cancer. In addition to germline high-penetrance mutations important in familial and hereditary breast cancer, a substantial component of breast cancer risk can be attributed to the combined effect of many low-risk germline polymorphisms involved in relevant pathways like those of DNA repair, adhesion, carcinogen and estrogen metabolism. Additionally, the identification of sequence variants in genes involved in response to chemotherapy and radiation treatment, has created the opportunity to apply genomics to individualized treatment.

Ionizing radiation modulates the exposure of the HUIV26 cryptic epitope within collagen type IV during angiogenesis.

Purpose: The majority of the research on the biologic effects of ionizing radiation has focused on the impact of radiation on cells in terms of gene expression, DNA damage, and cytotoxicity. In comparison, little information is available concerning the direct effects of radiation on the extracellular microenvironment, specifically the extracellular matrix and its main component, collagen. We have developed a series of monoclonal antibodies that bind to cryptic epitopes of collagen Type IV that are differentially exposed during matrix remodeling and are key mediators of angiogenesis.