Intraoperative Radiation Using Low-Kilovoltage X-Rays for Early Breast Cancer: A Single Site Trial.

INTRODUCTION: Two prospective, randomized trials, TARGIT-A and ELIOT, have shown intraoperative radiation therapy (IORT) to be a safe alternative to whole breast radiation therapy following breast-conserving surgery for selected low-risk patients. However, minimal data are available about the clinical effectiveness of this modality of treatment using the Xoft® Axxent® Electronic Brachytherapy (eBx®) System®. METHODS: A total of 201 patients with 204 early-stage breast cancers were enrolled in a prospective X-ray IORT trial from June 2010 to September 2013. All tumors were treated with breast-conserving surgery and IORT. Data were collected at 1 week, 1 month, 6 months, 1 year, and yearly thereafter. RESULTS: With a median follow-up of 50 months, there have been seven ipsilateral breast tumor events (IBTE), no regional or distant recurrences, and no breast cancer-related deaths. One IBTE was within the IORT field, four outside of the IORT field but within the same quadrant as the index cancer, and two were new biologically different cancers in different quadrants. Three events were in patients who deviated from the protocol criteria. Kaplan-Meier analysis projects that 2.9% of patients will recur locally at 4 years. CONCLUSIONS: Recurrence rates observed in this trial were comparable to those of the TARGIT-A and ELIOT trials as well as the retrospective TARGIT-R trial. The low complication rates previously reported by our group as well as the low recurrence rates reported in this study support the cautious use and continued study of IORT in selected women with low-risk breast cancer.

Acute and Chronic Complications in Breast Cancer Patients Treated with Intraoperative Radiation Therapy.

INTRODUCTION: Intraoperative radiation therapy (IORT) permits the delivery of radiation therapy directly to the tumor bed at the time of surgery. Minimal data are available about the complications associated with this modality of treatment using the Xoft(®) Axxent Electronic Brachytherapy (Axxent) System. METHODS: A total of 702 patients who received IORT using the Xoft(®) Axxent System at Hoag Memorial Hospital Presbyterian between June 2010-February 2016 were accrued in an IORT data registry study. The prospective and retrospective protocols were approved by the institutional review board and met the guidelines of their responsible governmental agency. Data were collected at 1 week, 1 month, 3 months, 6 months, 1 year, and thereafter yearly. Acute complications were defined as those occurring within the first month. Chronic complications were those that persisted beyond 6 months. RESULTS: Acute complications were observed in 21 % of patients and included hematomas that required drainage, seromas requiring drainage more than 3 times, infections treated with antibiotics or surgery, necrosis requiring surgery, and erythema. Chronic complications were observed in 13 % of patients and included seromas, fibrosis, and hyperpigmentation. The majority of acute and chronic problems from IORT were mild. If grade I erythema, fibrosis, and hyperpigmentation were removed, only 32 of 702 (4.6 %) had significant complications. Our complication rates were comparable to those of the TARGIT trial. CONCLUSIONS: IORT is a modality that safely delivers radiation therapy to patients diagnosed with breast cancer. This technique allows women who cannot (or decline to) undergo whole breast radiation to consider breast-conserving therapy rather than mastectomy.

Acute and Chronic Complications in Patients with Ductal Carcinoma in Situ Treated with Intraoperative Radiation Therapy.

Intraoperative radiation therapy (IORT) delivers radiation therapy directly to the tumor bed at the time of surgery. Minimal data are available regarding IORT complications in patients diagnosed with ductal carcinoma in situ (DCIS) using the Xoft® Axxent eBx® System. 146 patients with pure DCIS received X-ray based IORT therapy using the Xoft® Axxent eBx® System at Hoag Memorial Hospital Presbyterian between June 2010 to April 2016 and were accrued to an IORT data registry study. The protocols were approved by the institutional review board and met the guidelines of their responsible governmental agency. Data were collected at 1 week, 1 month, 6 months, 1 year, and thereafter yearly. Acute complications were defined as those occurring within the first month. Chronic complications were those that persisted beyond 6 months. Acute complications were observed in 18% of patients and included hematomas that required drainage, an infection treated with antibiotics, and erythema. Chronic complications were observed in 12% of patients and included a seroma, fibrosis and hyperpigmentation. The majority of acute and chronic problems were mild (Grade I). If Grade I erythema, fibrosis, and hyperpigmentation are not included, only 11/146 patients (7.5%) had significant complications. The rate of acute and chronic complications from X-ray IORT in DCIS patients was low compared to historical toxicity rates observed in DCIS patients treated with whole breast irradiation. Our data indicate that X-ray IORT can be utilized safely in patients diagnosed with DCIS.

A retrospective study of induction chemotherapy with docetaxel, cisplatinum, and 5-fluorouracil followed by concurrent radiotherapy with cetuximab in locally advanced head and neck cancer.

BACKGROUND: The objective was to study the results of induction chemotherapy followed by external beam radiation therapy with concurrent cetuximab in the treatment of locally advanced head and neck cancer. METHODS: Seventeen patients with stage III or IV squamous cell carcinomas of the head and neck who received docetaxel, cisplatinum, and 5-fluorouracil followed by radiation therapy with concurrent cetuximab were retrospectively analyzed. All radiation was delivered with image-guided intensity-modulated radiation treatments. Primary end points analyzed were local control and overall survival. RESULTS: With a median follow-up of 17 months, the approximate 2-year local control was 85%, with overall survival being 91%. At time of last follow-up, only 1 death was observed, with the cause of death unknown. Two local failures were observed, and the patients were under active management for their recurrences at time of last follow-up. No distant metastatic failures were noted among the patients. CONCLUSIONS: Induction chemotherapy with docetaxel, cisplatinum, and 5-fluorouracil followed by concurrent radiation with cetuximab provides for excellent locoregional control of disease. Future prospective studies can better establish the efficacy of this treatment regimen to current favored protocols.

Image-guided helical Tomotherapy for treatment of spine tumors.

OBJECTIVES: One of the most common indications for radiotherapy is treatment of the spine. The vast majority of cases are related to metastatic disease with primary tumors of the spine being rare. Conventional radiation therapy often plays an important role in the management of spine tumors although at times with significant side effects and disadvantages. Furthermore, retreatment of spine tumors is a challenge due to concerns over spinal cord toxicity. In this series, we examine the efficacy of using image-guided helical Tomotherapy and the possible advantages offered by this new technology. PATIENTS AND METHODS: Eight patients at Hoag Memorial Hospital Presbyterian were treated between November 2005 and November 2006. The median age was 66 years. Of the eight patients, seven had metastatic disease with one patient having a primary neuroendocrine tumor of the spine. Five patients were previously treated to the spine with conventional radiation planning. Two patients received single fraction stereotactic radiosurgery (15 Gy) while the remaining patients received hypofractionated stereotactic radiotherapy to a median total dose of 2,500 cGy in 500 cGy fractions. RESULTS: At the time of last follow-up, radiographic control was seen in all eight patients with a median local control rate of 2.5 months (range of 1-5.8 months). Four of the eight patients are still alive with median overall survival of 5.1 months (range 1.4-6.9 months). Acute toxicity ranged from Radiation Therapy Oncology Group (RTOG) score 0-2 and no patients experienced late complications of radiation myelitis. CONCLUSIONS: The TomoTherapy Hi-ART system can be an alternative treatment option for upfront or retreatment of spine tumors. Minimal acute and late toxicity were seen in patients treated with Tomotherapy. Intensity-modulated radiation delivery combined with megavoltage CT image guidance offered by the TomoTherapy Hi-ART system allows for set-up and delivery accuracy that is required for stereotactic treatment of spine tumors and eliminates the need for any internal or external fiducial marker placement.

Upfront boost Gamma Knife "leading-edge" radiosurgery to FLAIR MRI-defined tumor migration pathways in 174 patients with glioblastoma multiforme: a 15-year assessment of a novel therapy.

OBJECTIVE Glioblastoma multiforme (GBM) is composed of cells that migrate through the brain along predictable white matter pathways. Targeting white matter pathways adjacent to, and leading away from, the original contrast-enhancing tumor site (termed leading-edge radiosurgery [LERS]) with single-fraction stereotactic radiosurgery as a boost to standard therapy could limit the spread of glioma cells and improve clinical outcomes. METHODS Between December 2000 and May 2016, after an initial diagnosis of GBM and prior to or during standard radiation therapy and carmustine or temozolomide chemotherapy, 174 patients treated with radiosurgery to the leading edge (LE) of tumor cell migration were reviewed. The LE was defined as a region outside the contrast-enhancing tumor nidus, defined by FLAIR MRI. The median age of patients was 59 years (range 22-87 years). Patients underwent LERS a median of 18 days from original diagnosis. The median target volume of 48.5 cm3 (range 2.5-220.0 cm3) of LE tissue was targeted using a median dose of 8 Gy (range 6-14 Gy) at the 50% isodose line. RESULTS The median overall survival was 23 months (mean 43 months) from diagnosis. The 2-, 3-, 5-, 7-, and 10-year actual overall survival rates after LERS were 39%, 26%, 16%, 10%, and 4%, respectively. Nine percent of patients developed treatment-related imaging-documented changes due to LERS. Nineteen percent of patients were hospitalized for management of edema, 22% for resection of a tumor cyst or new tumor bulk, and 2% for shunting to treat hydrocephalus throughout the course of their disease. Of the patients still alive, Karnofsky Performance Scale scores remained stable in 90% of patients and decreased by 1-3 grades in 10% due to symptomatic treatment-related imaging changes. CONCLUSIONS LERS is a safe and effective upfront adjunctive therapy for patients with newly diagnosed GBM. Limitations of this study include a single-center experience and single-institution determination of the LE tumor target. Use of a leading-edge calculation algorithm will be described to achieve a consistent approach to defining the LE target for general use. A multicenter trial will further elucidate its value in the treatment of GBM.

Treatment of recurrent high grade gliomas with hypofractionated stereotactic image-guided helical tomotherapy.

OBJECTIVE: Salvage treatment of high grade gliomas that progress after standard therapy of resection and adjuvant chemoradiation therapy includes repeat surgical resection, second line chemotherapy, re-irradiation, or often a combination of the above. We present a series on patients treated with hypofractionated stereotactic image-guided helical tomotherapy and discuss the efficacy of this new technology in the treatment of high grade gliomas. MATERIALS AND METHODS: Between June 2005 and August of 2008, eight patients with recurrent high grade gliomas were treated with salvage radiation therapy using hypofractionated stereotactic image-guided helical tomotherapy after image documentation of disease progression. Median age was 48.5 years with 4 females and 4 males. Median KPS at time of treatment was 65. All patients had either Grade III or IV gliomas at time of treatment with previous history of involved field fractionated radiotherapy. Median total dose given was 2500cGy in 500cGy fractions. RESULTS: The median planning target volume was 69.5cm(3). Five of the eight patients were alive at the time of last follow-up with a median survival of 7.6 months. Radiographic documented control was seen in six of the eight patients with median local control of 4.6 months. Acute Radiation Therapy Oncology Group (RTOG) toxicity scores measured zero in all patients with only one patient requiring a reoperation following treatment. CONCLUSIONS: Hypofractionated stereotactic image-guided helical tomotherapy provides an alternative to other stereotactic radiation therapy and radiosurgery options for treatment of recurrent high grade gliomas.