Ashwatha Narayana

Bio: Ashwatha Narayana is an academic researcher from New York University. The author has contributed to research in topics: Radiosurgery & Radiation therapy. The author has an hindex of 29, co-authored 77 publications receiving 3558 citations. Previous affiliations of Ashwatha Narayana include Memorial Sloan Kettering Cancer Center & Cornell University.

Intensity-modulated radiation therapy for the treatment of oropharyngeal carcinoma: The Memorial Sloan-Kettering Cancer Center experience

Abstract: Purpose: To review the Memorial Sloan-Kettering Cancer Center’s experience in using intensity-modulated radiation therapy (IMRT) for the treatment of oropharyngeal cancer. Methods and Materials: Between September 1998 and June 2004, 50 patients with histologically confirmed cancer of the oropharynx underwent IMRT at our institution. There were 40 men and 10 women with a median age of 56 years (range, 28–78 years). The disease was Stage I in 1 patient (2%), Stage II in 3 patients (6%), Stage III in 7 (14%), and Stage IV in 39 (78%). Forty-eight patients (96%) received definitive treatment, and 2 (4%) were treated in the postoperative adjuvant setting. Concurrent chemotherapy was used in 43 patients (86%). Patients were treated using three different IMRT approaches: 76% dose painting, 18% concomitant boost with IMRT in both am and pm deliveries, and 6% concomitant boost with IMRT only in pm delivery. Regardless of the approach, the average prescription dose to the gross tumor planning target volume was 70 Gy, while the average dose delivered to the subclinical volume was 59.4 Gy in the dose painting group and 54 Gy in the concomitant boost group. Percutaneous endoscopic gastrostomy feeding tubes (PEGs) were placed before the beginning of treatment in 84% of the patients. Acute and late toxicity were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. Toxicity was also evaluated using subjective criteria such as the presence of esophageal stricture, and the need for PEG usage. The local progression-free, regional progression-free, and distant metastases-free rates, and overall survival were calculated using the Kaplan-Meier method. Results: Three patients had persistent locoregional disease after treatment. The 2-year estimates of local progression-free, regional progression-free, distant metastases-free, and overall survival were 98%, 88%, 84%, and 98%, respectively. The worst acute mucositis experienced was Grade 1 in 4 patients (8%), Grade 2 in 27 (54%), and Grade 3 in 19 (38%). Xerostomia decreased with increasing time interval from the end of radiotherapy, and among the patients with at least 9 months of follow-up there was 67% Grade 0–1 and 33% Grade 2 toxicity. Of the 42 patients who required upfront PEG placement, 6 were still using PEG for nutrition at the time of this analysis. Three patients had cervical esophageal strictures, and of these, 1 was still PEG dependent 1 year after treatment. Two of these patients were treated with the IMRT concomitant boost am and pm approach, whereas the other was treated with the dose painting technique. Conclusions: Intensity-modulated radiotherapy achieved encouraging local control rates in patients with oropharyngeal carcinoma. Treatment toxicity was acceptable even in the setting of concurrent chemotherapy. Long-term follow-up is needed to confirm these preliminary findings.

Central nervous system cancers: Clinical Practice Guidelines in Oncology.

Abstract: Primary and metastatic tumors of the central nervous system are a heterogeneous group of neoplasms with varied outcomes and management strategies. Recently, improved survival observed in 2 randomized clinical trials established combined chemotherapy and radiation as the new standard for treating patients with pure or mixed anaplastic oligodendroglioma harboring the 1p/19q codeletion. For metastatic disease, increasing evidence supports the efficacy of stereotactic radiosurgery in treating patients with multiple metastatic lesions but low overall tumor volume. These guidelines provide recommendations on the diagnosis and management of this group of diseases based on clinical evidence and panel consensus. This version includes expert advice on the management of low-grade infiltrative astrocytomas, oligodendrogliomas, anaplastic gliomas, glioblastomas, medulloblastomas, supratentorial primitive neuroectodermal tumors, and brain metastases. The full online version, available at NCCN.org, contains recommendations on additional subtypes.

Antiangiogenic therapy using bevacizumab in recurrent high-grade glioma: impact on local control and patient survival.

Abstract: Object Antiangiogenic agents have recently shown impressive radiological responses in high-grade glioma. However, it is not clear if the responses are related to vascular changes or due to antitumoral effects. The authors report the mature results of a clinical study of bevacizumab-based treatment of recurrent high-grade gliomas. Methods Sixty-one patients with recurrent high-grade gliomas received treatment with bevacizumab at 10 mg/ kg every 2 weeks for 4 doses in an 8-week cycle along with either irinotecan or carboplatin. The choice of concomitant chemotherapeutic agent was based on the number of recurrences and prior chemotherapy. Results At a median follow-up of 7.5 months (range 1–19 months), 50 (82%) of 61 patients relapsed and 42 patients (70%) died of the disease. The median number of administered bevacizumab cycles was 2 (range 1–7 cycles). The median progression-free survival (PFS) and overall survival (OS) were 5 (95% confidence interval [CI] 2.3–7.7) and 9 (95% CI 7.6–10.4) months, respectiv...

Resistance of Glioblastoma-Initiating Cells to Radiation Mediated by the Tumor Microenvironment Can Be Abolished by Inhibiting Transforming Growth Factor-β

Abstract: The poor prognosis of glioblastoma (GBM) routinely treated with ionizing radiation (IR) has been attributed to the relative radioresistance of glioma-initiating cells (GIC). Other studies indicate that although GIC are sensitive, the response is mediated by undefined factors in the microenvironment. GBM produce abundant transforming growth factor-β (TGF-β), a pleotropic cytokine that promotes effective DNA damage response. Consistent with this, radiation sensitivity, as measured by clonogenic assay of cultured murine (GL261) and human (U251, U87MG) glioma cell lines, increased by approximately 25% when treated with LY364947, a small-molecule inhibitor of TGF-β type I receptor kinase, before irradiation. Mice bearing GL261 flank tumors treated with 1D11, a pan-isoform TGF-β neutralizing antibody, exhibited significantly increased tumor growth delay following IR. GL261 neurosphere cultures were used to evaluate GIC. LY364947 had no effect on the primary or secondary neurosphere-forming capacity. IR decreased primary neurosphere formation by 28%, but did not reduce secondary neurosphere formation. In contrast, LY364947 treatment before IR decreased primary neurosphere formation by 75% and secondary neurosphere formation by 68%. Notably, GL261 neurospheres produced 3.7-fold more TGF-β per cell compared with conventional culture, suggesting that TGF-β production by GIC promotes effective DNA damage response and self-renewal, which creates microenvironment-mediated resistance. Consistent with this, LY364947 treatment in irradiated GL261 neurosphere-derived cells decreased DNA damage responses, H2AX and p53 phosphorylation, and induction of self-renewal signals, Notch1 and CXCR4. These data motivate the use of TGF-β inhibitors with radiation to improve therapeutic response in patients with GBM.

Salvage Re-Irradiation for Recurrent Head and Neck Cancer

Abstract: Purpose: To present a retrospective review of treatment outcomes for recurrent head and neck (HN) cancer patients treated with re-irradiation (re-RT) at a single medical center. Methods and Materials: From July 1996–September 2005, 105 patients with recurrent HN cancer underwent re-RT at our institution. Sites included were: the neck ( n = 21), nasopharynx ( n = 21), paranasal sinus ( n = 18), oropharynx ( n = 16), oral cavity ( n = 9), larynx ( n = 10), parotid ( n = 6), and hypopharynx ( n = 4). The median prior RT dose was 62 Gy. Seventy-five patients received chemotherapy with their re-RT (platinum-based in the majority of cases). The median re-RT dose was 59.4 Gy. In 74 (70%), re-RT utilized intensity-modulated radiation therapy (IMRT). Results: With a median follow-up of 35 months, 18 patients were alive with no evidence of disease. The 2-year loco-regional progression-free survival (LRPFS) and overall survival rates were 42% and 37%, respectively. Patients who underwent IMRT, compared to those who did not, had a better 2-year LRPF (52% vs. 20%, p p Conclusions: Based on our data, achieving LR control is crucial for improved overall survival in this patient population. The use of IMRT predicted better LR tumor control. Future aggressive efforts in maximizing tumor control in the recurrent setting, including dose escalation with IMRT and improved chemotherapy, are warranted.

Malignant Gliomas in Adults

Abstract: Approximately 5% of patients with malignant gliomas have a family history of gliomas. Some of these familial cases are associated with rare genetic syndromes, such as neurofibromatosis types 1 and 2, the Li−Fraumeni syndrome (germ-line p53 mutations associated with an increased risk of several cancers), and Turcot’s syndrome (intestinal polyposis and brain tumors). 10 However, most familial cases have

Updated Response Assessment Criteria for High-Grade Gliomas: Response Assessment in Neuro-Oncology Working Group

Abstract: Currently, the most widely used criteria for assessing response to therapy in high-grade gliomas are based on two-dimensional tumor measurements on computed tomography (CT) or magnetic resonance imaging (MRI), in conjunction with clinical assessment and corticosteroid dose (the Macdonald Criteria). It is increasingly apparent that there are significant limitations to these criteria, which only address the contrast-enhancing component of the tumor. For example, chemoradiotherapy for newly diagnosed glioblastomas results in transient increase in tumor enhancement (pseudoprogression) in 20% to 30% of patients, which is difficult to differentiate from true tumor progression. Antiangiogenic agents produce high radiographic response rates, as defined by a rapid decrease in contrast enhancement on CT/MRI that occurs within days of initiation of treatment and that is partly a result of reduced vascular permeability to contrast agents rather than a true antitumor effect. In addition, a subset of patients treated with antiangiogenic agents develop tumor recurrence characterized by an increase in the nonenhancing component depicted on T2-weighted/fluid-attenuated inversion recovery sequences. The recognition that contrast enhancement is nonspecific and may not always be a true surrogate of tumor response and the need to account for the nonenhancing component of the tumor mandate that new criteria be developed and validated to permit accurate assessment of the efficacy of novel therapies. The Response Assessment in Neuro-Oncology Working Group is an international effort to develop new standardized response criteria for clinical trials in brain tumors. In this proposal, we present the recommendations for updated response criteria for high-grade gliomas.