Richard C. Zellars, MD

Breast conserving therapy (BCT), defined as lumpectomy and adjuvant whole breast irradiation (WBI), is integral in the management of early-stage breast cancer. Although BCT offers equivalent survival for the large majority of women with early-stage breast cancer, many women choose mastectomy simply out of convenience, as the standard 5-7 week course of radiation results in lost time from loved ones and livelihood. To allow more freedom in choosing the local therapy, researchers are investigating treatment methods that would facilitate therapy. One such method is partial breast irradiation (PBI). Treating only part of the breast would allow the radiation oncologist to deliver therapeutic doses of radiation in far less time than would be possible when treating the whole breast.

There are several clinical trials that will definitively influence the future use of PBI. While these and other preliminary reports suggest that PBI has comparable outcomes to WBI, there is growing evidence that PBI may not be appropriate for a subpopulation of patients. Studies have also found an association between increased recurrence and estrogen receptor negative tumors.

In all the above trials, chemotherapy, if given, was delivered either before or after PBI. No trial yet has delivered chemotherapy concurrently with PBI, because of the prohibitive radiation toxicity associated with concurrent WBI and chemotherapy. However, because of the reduced toxicities of PBI as compared with WBI, Dr. Zellars and colleagues believe that there are real and potential benefits of delivering chemotherapy concurrently with PBI. These benefits include: 1) a reduction in overall treatment duration; 2) both modalities would start temporally closer to surgery which theoretically maximizes the benefits of each; and 3) possibly improved local control via the radiation sensitizing effects of chemotherapy.

Through previous BCRF grants, Dr. Zellars's team has been able to conduct two phase I trials of PBI and concurrent chemotherapy (PBICC) to test whether toxicity remained prohibitive with this combined modality therapy. In the first trial, 25 patients were treated with PBI and concurrent dose dense doxorubicin and cyclophosphamide. In the second trial, 34 patients were treated similarly but this time the chemotherapy regimen was at the discretion of the treating medical oncologist. Both trials revealed that PBICC is well tolerated. Specifically, there was no grade 3 or 4 acute or late radiation induced toxicity in either trial. Dr. Zellars's group has reported and published these findings from their phase I trials.

In 2012-2013, Dr. Zellars's team will continue to assess the safety and feasibility of PBICCC. Based on previous results, they hypothesize that women with ER- early-stage breast cancer and treated with PBI and concurrent chemotherapy will have local control rates similar to women with ER positive disease. They will conduct a single-arm phase II trial of PBICC in women with ER negative early-stage breast cancer. They will assess acute and late loco-regional and systemic toxicity in women treated with PBICC, as well as perform molecular analyses to determine multi-molecular predictors for local failure and for adverse toxicity in collaboration with fellow BCRF grantee, Dr. Andrew Quong (Thomas Jefferson University School of Medicine). If their trial is successful, Dr. Zellars's work will provide an additional therapeutic option for women with ER- early-stage breast cancer.

Mid-year Progress: In his work on partial breast irradiation and concurrent chemotherapy (PBICC), Dr. Zellars presented abstracts showing very low rates of toxicity with PBICC at two recent international meetings. Additionally, his team showed lower than expected rates of local recurrence in high-risk triple negative and ER negative tumors when treated with PBICC. Consequently, Dr. Zellars is completing the design of a larger trial to further assess the efficacy of this novel combination of therapies and expect it to open for accrual by May 2013.

Continuing his ongoing research on SPECT, Dr. Zellars's team recently obtained results which suggesting that cardiac tissue may be far more sensitive to radiation than previously believed. They confirmed the original results of the trial when their recently completed second method of analysis reported similar findings. Two manuscripts detailing the results are nearing completion.

Also, based on the results of their study on ultrasound elasticity imaging, Dr. Zellars's team was able to further develop ultrasound elasticity imaging. The resulting newly designed elasticity algorithm will be used to evaluate tumor response to concurrent PARP inhibitor treatment and irradiation (POPI) in women who had an incomplete response to neoadjuvant chemotherapy. Dr. Zellars's goal is to define imaging characteristics that will be predictive of tumor response.

In addition, approximately 61 patients have been enrolled in Dr. Zellars's study of cytokine expression changes during radiation treatment for breast cancer. Complete accrual is expected in six to eight months. Thus far, the team has found changes in expression of certain cytokines and proteins that occur during the course of whole breast radiation.

Bio:
Dr. Zellars is a graduate of the Johns Hopkins School of Medicine. He completed his residency at the University of Michigan in the Department of Radiation Oncology, where he was Chief Resident from 1995-96. He next accepted an appointment as an Assistant Professor of Radiation Oncology at the University of Texas Health Science Center in San Antonio. During his tenure there, Dr. Zellars also served as Clinic Director and Vice Chair. Before returning to Johns Hopkins and the Sidney Kimmel Comprehensive Cancer Center, he was at Georgetown University Department of Radiation Medicine. Currently, Dr. Zellars is Associate Professor in the Department of Radiation Oncology and Molecular Radiation Sciences at Hopkins. In January 2013, Dr. Zellars was appointed Assistant Director for Clinical Trials Accrual at the Sidney Kimmel Comprehensive Cancer Center, where he will focus on the recruitment of minority patients to clinical trials.

Dr. Zellars's primary research interests are the evaluation of putative prognostic factors for local failure and the development of new radiation therapy techniques, all with respect to breast cancer.