Stuti Ahlawat

Characterization of folate uptake by choroid plexus epithelial cells in a rat primary culture model

J. Neurochem. (2008) 104, 1494–1503.

Riluzole Enhances Ionizing Radiation–Induced Cytotoxicity in Human Melanoma Cells that Ectopically Express Metabotropic Glutamate Receptor 1 In Vitro and In Vivo

Purpose: Brain metastases are a common preterminal event in patients with metastatic melanoma and require radiation therapy. Our group has previously shown that human GRM1 (hGRM1) expressing melanoma cells release excess extracellular glutamate and are growth inhibited by riluzole, an inhibitor of glutamate release. Riluzole-treated cells accumulate in G2/M phase of the cell cycle at 24 hours, and then undergo apoptotic cell death. We evaluated whether riluzole enhanced radiosensitivity in melanoma cells. Experimental Design: Clonogenic assays were performed to evaluate clonogenic survival after treatment in hGRM1 expressing and nonexpressing melanoma cells. Western immunoblots were performed to confirm apoptotic cell death. A xenograft mouse model was used to validate the in vitro experiments. Tumors harvested from the xenografts were fixed and stained for apoptosis and DNA damage markers. Results: In the hGRM1-positive cell lines C8161 and UACC903, riluzole enhanced the lethal effects of ionizing radiation; no difference was seen in the hGRM1-negative UACC930 cell line. C8161 cells treated with riluzole plus irradiation also showed the highest levels of the cleaved forms of PARP and caspase-3; excised C8161 xenografts showed the greatest number of apoptotic cells by immunohistochemistry (P < 0.001). On cell cycle analysis, a sequence-dependent enrichment in the G2/M phase was shown with the combination of riluzole and irradiation. Xenografts treated with riluzole and weekly radiation fractions showed significant growth inhibition and revealed markedly increased DNA damage. Conclusions: We have shown, in vitro and in vivo, that the combination of riluzole and ionizing radiation leads to greater cytotoxicity. These results have clinical implications for patients with brain metastases receiving whole brain radiation therapy. Clin Cancer Res; 17(7); 1807–14. ©2011 AACR.

Short-Course Hypofractionated Radiation Therapy With Boost in Women With Stages 0 to IIIa Breast Cancer: A Phase 2 Trial

PURPOSE Conventionally fractionated whole-breast irradiation (WBI) with a boost takes approximately 6 to 7 weeks. We evaluated a short course of hypofractionated (HF), accelerated WBI in which therapy was completed in 3 weeks inclusive of a sequential boost. METHODS AND MATERIALS We delivered a whole-breast dose of 36.63 Gy in 11 fractions of 3.33 Gy over 11 days, followed by a lumpectomy bed boost in 4 fractions of 3.33 Gy delivered once daily for a total of 15 treatment days. Acute toxicities were scored using Common Terminology Criteria for Adverse Events version 4. Late toxicities were scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale. Cosmesis was scored using the Harvard Cosmesis Scale. Our primary endpoint was freedom from locoregional failure; we incorporated early stopping criteria based on predefined toxicity thresholds. Cosmesis was examined as a secondary endpoint. RESULTS We enrolled 83 women with stages 0 to IIIa breast cancer. After a median follow-up of 40 months, 2 cases of isolated ipsilateral breast tumor recurrence occurred (2 of 83; crude rate, 2.4%). Three-year estimated local recurrence-free survival was 95.9% (95% confidence interval [CI]: 87.8%-98.7%). The 3-year estimated distant recurrence-free survival was 97.3% (95% CI: 89.8%-99.3%). Three-year secondary malignancy-free survival was 94.3% (95% CI: 85.3%-97.8%). Twenty-nine patients (34%) had grade 2 acute toxicity, and 1 patient had a late grade 2 toxicity (fibrosis). One patient had acute grade 3 dermatitis, whereas 2 patients experienced grade 3 late skin toxicity. Ninety-four percent of evaluable patients had good or excellent cosmesis. CONCLUSIONS Our phase 2 institutional study offers one of the shortest courses of HF therapy, delivered in 15 fractions inclusive of a sequential boost. We demonstrated expected low toxicity and high local control rates with good to excellent cosmetic outcomes. This fractionation scheme is feasible and well tolerated and offers women WBI in a highly convenient schedule.

The role of MRI in the follow-up of women undergoing breast-conserving therapy

Objectives:Breast-conserving therapy (BCT) represents a standard of care in the management of breast cancer. However, unlike mastectomy, women treated with BCT require follow-up imaging of the treated breast as well as the contralateral breast as part of posttreatment surveillance. Traditionally, surveillance has consisted of clinical exams and mammograms. However, magnetic resonance imaging (MRI) has emerged as a breast imaging technique utilized as part of high-risk screening programs as well as part of the initial diagnosis and workup of women considered for BCT. At this time, the role of MRI as part of follow-up for women treated with BCT remains unclear. Methods:A systematic review was performed to evaluate the role of MRI following BCT. Results:Although there is no randomized evidence supporting the routine use of MRI in surveillance post-BCT, a review of the literature demonstrates that MRI (1) has increased sensitivity as compared with mammography to detect recurrences, and (2) can help evaluate mammographic abnormalities before biopsy and/or surgery. Conclusions:In patients with higher risk of local recurrence, surveillance with MRI may represent an effective surveillance strategy though subgroups benefiting have not been identified nor has the impact on quality of life and cost been evaluated.

Ultrashort Courses of Breast Radiotherapy

A review of current intraoperative and ultrashort radiotherapy schedules for the treatment of breast cancer is presented. Both the promise and the pitfalls of this strategy are reviewed.

Novel and Highly Compressed Schedules for the Treatment of Breast Cancer

Our thinking about radiotherapy (RT) for early-stage breast cancer has evolved considerably over the last several years. Increasingly patients and physicians together are making the decision to use altered fractionation rather than standard 6-7 weeks of conventional whole breast treatment plus lumpectomy bed boost. Adjuvant hypofractionated whole breast irradiation is now viewed as a preferred strategy for many eligible women, and can be completed in 3-4 weeks. Adjuvant accelerated partial breast irradiation is another alternative that is typically delivered in 8-10 fractions over 4-5 days. With improvements in delivery techniques, there has been renewed interest in shortening treatment times even further, with novel intraoperative approaches and ultrashort courses of external beam RT. This article provides a summary of the status and future directions in intraoperative and ultrashort course RT schedules used in the treatment of breast cancer. Outlined are the benefits as well as the drawbacks of these techniques for abbreviated breast RT.