Delivery efficiency of an Elekta linac under gated operation.

In this study, we have characterized the efficiency of an Elekta linac in the delivery of gated radiotherapy. We have explored techniques to reduce the beam-on delay and to improve the delivery efficiency, and have investigated the impact of frequent beam interruptions on the dosimetric accuracy of gated deliveries. A newly available gating interface was installed on an Elekta Synergy. Gating signals were generated using a surface mapping system in conjunction with a respiratory motion phantom. A series of gated deliveries were performed using volumetric modulated arc therapy (VMAT) treatment plans previously generated for lung cancer patients treated with stereotactic body radiotherapy. Baseline values were determined for the delivery times. The machine was then tuned in an effort to minimize beam-on delays and improve delivery efficiency. After that process was completed, the dosimetric accuracy of the gated deliveries was evaluated by comparing the measured and the planned coronal dose distributions using gamma index analyses. Comparison of the gated and the non-gated deliveries were also performed. The results demonstrated that, with the optimal machine settings, the average beam-on delay was reduced to less than 0.22 s. High dosimetric accuracy was demonstrated with gamma index passing rates no lower than 99.0% for all tests (3%/3 mm criteria). Consequently, Elekta linacs can provide a practical solution for gated VMAT treatments with high dosimetric accuracy and only a moderate increase in the overall delivery time.

Phase I study of stereotactic radiosurgery in patients with locally advanced pancreatic cancer.

PURPOSE: To determine the feasibility and toxicity of delivering stereotactic radiosurgery to patients with locally advanced pancreatic cancer. METHODS AND MATERIALS: Patients with Eastern Cooperative Oncology Group performance status < or=2 and locally advanced pancreatic cancer were enrolled on this Phase I dose escalation study. Patients received a single fraction of radiosurgery consisting of either 15 Gy, 20 Gy, or 25 Gy to the primary tumor. Acute gastrointestinal toxicity was scored according to the Radiation Therapy Oncology Group criteria. Response to treatment was determined by serial high-resolution computed tomography scanning. RESULTS: Fifteen patients were treated at 3 dose levels (3 patients received 15 Gy, 5 patients received 20 Gy, and 7 patients received 25 Gy). At these doses, no Grade 3 or higher acute gastrointestinal toxicity was observed. This trial was stopped before any dose-limiting toxicity was reached, because the clinical objective of local control was achieved in all 6 evaluable patients treated at 25 Gy. CONCLUSIONS: It is feasible to deliver stereotactic radiosurgery to patients with locally advanced pancreatic cancer. The recommended dose to achieve local control without significant acute gastrointestinal toxicity is 25 Gy.

Phase II trial of preoperative 3D conformal radiotherapy, protracted venous infusion 5-fluorouracil, and weekly CPT-11, followed by surgery for ultrasound-staged T3 rectal cancer.

PURPOSE: CPT-11 sensitizes tumor cells to radiation and in combination therapy with 5-fluorouracil (5-FU) results in enhanced cytotoxicity to metastatic colorectal cancer. We report the results from a Phase II trial of preoperative radiotherapy (RT), CPT-11, and 5-FU for patients with ultrasound-staged T3 rectal cancer. METHODS AND MATERIALS: Between April 1999 and August 2001, 32 patients (21 men, 11 women; median age 52 years, range 40-74) with biopsy-proven adenocarcinoma of the rectum were enrolled in the study. All patients underwent endorectal ultrasonography for staging (uT3N0 = 19; uT3N1 = 13; uT2N1 = 1). RT was prescribed to the draining lymph nodes (45 Gy in 1.8-Gy daily fractions) and tumor (50.4 Gy in 1.8-Gy daily fractions). Patients also received concurrent CPT-11 (50 mg/m(2), Days 1, 8, 15, and 22) and 5-FU (200 mg/m(2) daily, 7 d/wk, Days 1-33). Surgical resection was performed 6-10 weeks after completing chemoradiotherapy. RESULTS: Acute toxicity was frequently observed, and 18 patients (56%) required either a chemotherapy dose reduction or RT interruption of >3 days. One patient withdrew because of diarrhea and abdominal cramping (Grade III) after 10 days of treatment. Although no Grade IV toxicity was observed, Grade III diarrhea (n = 9, 28%), mucositis (n = 7, 21%), rectal sores (n = 7, 21%), abdominal cramping (n = 3, 9%) were noted. Of the 32 patients who underwent surgery, 12 had a complete pathologic response. Of the 32 patients, the disease of 23 (71%) was downstaged. The average length of hospitalization was between 5 and 12 days, with 1 patient staying 33 days. All patients were followed for disease-free survival. CONCLUSION: Although associated with frequent acute toxicity, the regimen is associated with significant tumor "downstaging." Additional patients and longer follow-up are necessary to define the role of this regimen fully.

Image guided stereotactic radiosurgery for lesions in proximity to the anterior visual pathways: a preliminary report.

The incidence of optic neuropathy after stereotactic radiosurgery (SRS) is related to the total dose, fraction size, and treatment volume. Theoretically, fractionated SRS can decrease this risk. In this paper, we report our technique for fractionated SRS and assess its potential role in the management of tumors located adjacent to the anterior visual pathways. Since 1997, thirteen patients (median age: 50, range 21-76) with lesions in close proximity to the anterior visual pathways were treated on the CyberKnife image guided SRS system (Accuray, Inc., Sunnyvale, CA). The CyberKnife is a 6MV linear accelerator mounted on a robotic arm which can monitor and adjust to changes in the target position in real time thus eliminating skeletal frame immobilization and allowing for convenient multi-fraction SRS treatments. Magnetic Resonance Imaging (MRI) and computerized tomography (CT) imaging for treatment planning were obtained with the patients head immobilized in an aquaplast mask. After image fusion, the target and critical structures were delineated. Two to five fractions were prescribed with approximately a 24-hour interfraction interval. The patients received 25 Gy in 5 fractions (n=5), 21 Gy in 3 fractions (n=5), or 20 Gy in 2 fractions (n=3) to the 75-95% isodose line. Ten of the thirteen patients had good pretreatment vision. In nearly all instances, the volume of the optic nerve that received 80% of the prescribed dose was < 0.05 cm3. In all instances, the volume of the optic nerve that received 50% of the prescribed dose was 0.03 cm3 of optic nerve. With median follow up of 18 months (range 12 to 54), four patients have had improvement in their vision. No visual deterioration has been observed in any of the other patients. In addition, there has been no tumor progression within the treated field. Fractionated SRS using the CyberKnife is technically feasible and may decrease the risk of optic neuropathy. Greater patient accrual and longer follow up will be necessary to further determine the clinical benefit of this approach.

Radiotherapy and erlotinib combined: review of the preclinical and clinical evidence.

Epidermal growth factor receptor (EGFR) is often overexpressed in tumors and has been associated with poor prognosis in some cancer types. The introduction of inhibitors of EGFR, such as erlotinib, represents an important recent advance in the targeted treatment of cancer. Several studies have evaluated inhibitors of EGFR in combination with radiotherapy, and a strong biologic rationale exists for the use of this combination in certain cancer types, including head and neck squamous cell carcinoma, non-small cell lung cancer, glioblastoma, esophageal cancer, and pancreatic cancer. Preclinical and clinical studies are underway to evaluate the combination of erlotinib with radiotherapy. To date, the results suggest that this approach is at least feasible and may result in modest improvement in outcomes compared with either modality alone.

Experience with an electronic brachytherapy technique for intracavitary accelerated partial breast irradiation.

OBJECTIVES: Phase IV study evaluated the safety and device performance of an electronic brachytherapy system (Axxent Electronic Brachytherapy System) as adjuvant therapy for early-stage breast cancer. METHODS: Patients were > or =50 years of age and had completely resected invasive ductal carcinoma or ductal carcinoma in situ (<2.0 cm), with N0 M0 and negative microscopic margins of > or =1 mm. The balloon applicator was placed in a closed cavity with a balloon surface to skin distance of > or =7 mm. The prescribed dose was 3.4 Gy/fraction prescribed to 1 cm beyond the balloon surface twice daily (BID) for 10 fractions. RESULTS: Of 65 patients consented, 21 (32%) were not eligible for treatment, and 44 (68%) were treated, with 6-months follow-up in 43 and 1-year follow-up in 36. The prescribed radiation treatment was successfully delivered in 42/44 (95.4%) patients; one was unsuccessful due to a controller issue and the other declined the final fraction following a balloon deflation. Side effects were as anticipated and generally manageable. Four CTCAE v3 grade 3 toxicities were reported: blistering (1), breast tenderness (1), and moist desquamation (2); all have resolved. The most common grade 2 toxicity was erythema. There were no device-related serious adverse events. CONCLUSIONS: Early experience demonstrates that the electronic brachytherapy system performed as expected. Electronic brachytherapy has similar acute toxicity profiles to other high dose rate approaches for accelerated partial breast irradiation and offers the convenience of having the treatment in an unshielded room.

Postmastectomy radiation therapy after TRAM flap breast reconstruction.

Postmastectomy chest wall and nodal radiation therapy decreases local recurrence and improves disease-free and overall survival. Immediate transverse rectus abdominis myocutaneous (TRAM) flap breast reconstruction after mastectomy has become more common. We report on our experience of irradiating the chest wall and regional lymph nodes after a TRAM flap reconstruction and describe the acute side effects, flap viability, and cosmetic outcome. Between 1995 and 2000, 22 patients with a median age of 47 years (range 27-61 years) received chest wall radiotherapy following mastectomy and immediate pedicled TRAM flap reconstruction. The indication for radiotherapy included tumor size, involved lymph nodes, or positive margins. All patients received chemotherapy before radiotherapy and three patients also received concurrent chemotherapy. The median dose to the chest wall was 50.4 Gy in 28 fractions of 1.8 Gy using a 6 or 4 MV linear accelerator. The patients were all computed tomography (CT) planned in the treatment position. The patients were immobilized using an alpha cradle. Two tangent fields were used to deliver the dose. On alternating days, a customized bolus was applied to the chest wall that spared the central region where the subsequent nipple reconstruction would be performed. All 22 patients completed 90% of the prescribed chest wall radiotherapy dose. Sixty-six percent of the patients received treatment without any treatment breaks. Only 10% of the patients developed desquamation of the TRAM flap skin. Thirty percent developed grade II erythema of the TRAM flap. With median follow-up of 18 months, no TRAM flaps have been lost or required revision. This technique for delivery of radiotherapy to the chest wall in patients who have undergone a mastectomy and immediate TRAM flap reconstruction is well tolerated. The acute toxicity was manageable. There were no TRAM flap losses or revisions performed secondary to the radiotherapy.