J.V. Kuo

Endoscopic ultrasound delivery of an antitumor agent to treat a case of pancreatic cancer

Background A 72-year-old white male presented to a University Digestive Disease Center with epigastric pain and weight loss. A CT scan suggested that the patient had a mass in his pancreas and he was referred for further diagnostic work-up, staging and treatment.Investigations Endoscopic ultrasound (EUS), EUS-guided fine-needle aspirationDiagnosis Locally advanced, unresectable adenocarcinoma of the pancreasManagement Opioid analgesics and EUS-guided celiac neurolysis (transgastric injection of bupivacaine and alcohol on both sides of the celiac artery) for pain relief. Five once-weekly intratumoral injections of TNFerade™ (GenVec, Inc., Gaithersburg, MD) by EUS-guided fine needle injection, in combination with chemoradiation (5 FU/XRT), as part of a multicenter clinical trial. Repeat fine-needle aspiration followed by surgical resection of the tumor.

Intensity-modulated radiotherapy for previously irradiated, recurrent head-and-neck cancer

The purpose of this work is to evaluate our initial experience in treating previously irradiated, recurrent head-and-neck cancers using intensity-modulated radiotherapy (IMRT). Between July 1997 and September 1999, 12 patients with previously irradiated, locally recurrent head-and-neck cancers were treated with IMRT. These included cancers of the nasopharynx, oropharynx, hypopharynx, larynx, paranasal sinus, skin of the head-and-neck region, and malignant melanoma. Five of these 12 patients had received radiation as the primary treatment, with doses ranging from 66.0 to 126.0 Gy, and the remaining 7 patients had undergone definitive surgeries followed by an adjuvant course of radiation treatment, with doses ranging between 36.0 and 64.8 Gy. Recurrence after the initial course of radiation occurred in periods ranging from 4 to 35 months, with 11 of 12 cases recurring fully in the fields of previous irradiation. Recurrent tumors were treated with IMRT to total doses between 30 to 70 Gy (> 50 Gy in 10 cases) prescribed at the 75% to 92% isodose lines with daily fractions of 1.8 to 2 Gy. The results revealed that acute toxicities were acceptable except in 1 patient who died of aspiration pneumonia during the course of retreatment. There were 4 complete responders, 2 partial responders, and 2 patients with stable disease in the IMRT-treated volumes. Three patients received IMRT as adjuvant treatment following salvage surgery. At 4 to 16 months of follow-up, 7 patients were still alive, with 5 revealing no evidence of disease. In conclusion, this pilot study demonstrates that IMRT offers a viable mode of re-irradiation for recurrent head-and-neck cancers in previously irradiated sites. Longer follow-up time and a larger number of patients are needed to better define the therapeutic advantage of IMRT in recurrent, previously irradiated head-and-neck cancers.

The use of RapidArc volumetric-modulated arc therapy to deliver stereotactic radiosurgery and stereotactic body radiotherapy to intracranial and extracranial targets

Twenty-three targets in 16 patients treated with stereotactic radiosurgery (SRS) or stereotactic body radiotherapy (SBRT) were analyzed in terms of dosimetric homogeneity, target conformity, organ-at-risk (OAR) sparing, monitor unit (MU) usage, and beam-on time per fraction using RapidArc volumetric-modulated arc therapy (VMAT) vs. multifield sliding-window intensity-modulated radiation therapy (IMRT). Patients underwent computed tomography simulation with site-specific immobilization. Magnetic resonance imaging fusion and optical tracking were incorporated as clinically indicated. Treatment planning was performed using Eclipse v8.6 to generate sliding-window IMRT and 1-arc and 2-arc RapidArc plans. Dosimetric parameters used for target analysis were RTOG conformity index (CI(RTOG)), homogeneity index (HI(RTOG)), inverse Paddick Conformity Index (PCI), D(mean) and D5-D95. OAR sparing was analyzed in terms of D(max) and D(mean). Treatment delivery was evaluated based on measured beam-on times delivered on a Varian Trilogy linear accelerator and recorded MU values. Dosimetric conformity, homogeneity, and OAR sparing were comparable between IMRT, 1-arc RapidArc and 2-arc RapidArc plans. Mean beam-on times ± SD for IMRT and 1-arc and 2-arc treatments were 10.5 ± 7.3, 2.6 ± 1.6, and 3.0 ± 1.1 minutes, respectively. Mean MUs were 3041, 1774, and 1676 for IMRT, 1-, and 2-arc plans, respectively. Although dosimetric conformity, homogeneity, and OAR sparing were similar between these techniques, SRS and SBRT fractions treated with RapidArc were delivered with substantially less beam-on time and fewer MUs than IMRT. The rapid delivery of SRS and SBRT with RapidArc improved workflow on the linac with these otherwise time-consuming treatments and limited the potential for intrafraction organ and patient motion, which can cause significant dosimetric errors. These clinically important advantages make image-guided RapidArc useful in the delivery of SRS and SBRT to intracranial and extracranial targets.

Outcomes of High-Dose-Rate Interstitial Brachytherapy in the Treatment of Locally Advanced Cervical Cancer: Long-term Results

PURPOSE The purpose of this study was to determine locoregional control (LRC), disease-free survival (DFS), and toxicity of high-dose-rate interstitial brachytherapy (HDR-ISBT) in the treatment of locally advanced cervical cancer. METHODS AND MATERIALS Between March 1996 and May 2009, 116 patients with cervical cancer were treated. Of these, 106 (91%) patients had advanced disease (International Federation of Gynecology and Obstetrics stage IIB-IVA). Ten patients had stage IB, 48 had stage II, 51 had stage III, and 7 had stage IVA disease. All patients were treated with a combination of external beam radiation therapy (EBRT) to the pelvis (5040 cGy) and 2 applications of HDR-ISBT to a dose of 3600 cGy to the implanted volume. Sixty-one percent of patients also received interstitial hyperthermia, and 94 (81%) patients received chemotherapy. RESULTS Clinical LRC was achieved in 99 (85.3%) patients. Three-year DFS rates were 59%, 67%, 71%, and 57% for patients with stage IB, II, III, and IVA disease, respectively. The 5-year DFS and overall survival rates for the entire group were 60% and 44%, respectively. Acute and late toxicities were within acceptable limits. CONCLUSIONS Locally advanced cervical cancer patients for whom intracavitary BT is unsuitable can achieve excellent LRC and OS with a combination of EBRT and HDR-ISBT.

Intensity-modulated radiation therapy for the spine at the University of California, Irvine

Radiation treatment of malignant diseases of the spine poses unique challenges to the radiation oncology treatment team. Intensity-modulated radiation therapy (IMRT) offers the capability of delivering high doses to targets near the spine while respecting spinal cord tolerance. At the University of California, Irvine, 8 patients received a total of 10 courses to the spine for a variety of primary and metastatic malignant conditions. This paper discusses anatomical considerations, spinal cord radiation myelopathy, and treatment planning issues as it relates to the treatment of spinal cord lesions. Between October 1997 and August 2001, a total of 8 patients received 10 courses of IMRT for primary or metastatic disease of the spine. Cancers treated included metastatic lung, renal, adrenocortical cancers, and primary sarcomas and giant cell tumor. Five cases had 6 courses given for re-irradiation of symptomatic disease and 3 cases had 4 courses of IMRT as primary management of their spinal lesions. Although 3 courses were given postoperatively, these were for grossly residual disease. For the re-irradiation patients, the mean follow-up interval was 4 months. The local control was estimated at 14%. Of the patients treated with primary intent, the mean follow-up was 9 months and the local control rate 75%. No patients developed spinal cord complications.

A feasibility study of topotecan with standard-dose cisplatin and concurrent primary radiation therapy in locally advanced cervical cancer

OBJECTIVES Topotecan improves response rate (RR), progression-free survival (PFS) and overall survival (OS) when added to cisplatin in treating metastatic and recurrent cervical cancer. The objective of this study was to assess the feasibility of adding weekly topotecan to cisplatin in patients with primary, locally advanced carcinoma of the cervix receiving pelvic irradiation. METHODS Patients with primary, previously untreated, histologically confirmed invasive squamous cell, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix, stages IB2-IVA were treated with external beam pelvic radiotherapy (45 Gy), intracavitary low dose rate brachytherapy (40 Gy) and a parametrial boost (5.4-9 Gy) with overall treatment time not to exceed 8 weeks. Concurrent chemotherapy was IV cisplatin 40 mg/m(2)plus IV topotecan 2 mg/m(2) on days 1, 8, 15, 22, 29 and once during parametrial boost for 6 cycles. Patients were monitored with history, physical examination, tumor measurement and laboratory evaluation before entering the study, before each cycle of chemotherapy, at study termination and every three months thereafter. RESULTS The study met its accrual goal of 12 patients. With a median follow-up of 22 months, eleven patients completed treatment and ten are in long term follow up without evidence of recurrent disease. The 12th patient developed progressive disease during therapy. All patients completed at least 4 cycles of chemotherapy, with the majority (82%) completing 5 or more. Grade 2 or higher neutropenia delayed treatment in 54% of cycles. The median treatment delay was 1.5 cycles (range: 1 to 5 cycles). Median treatment time was 59 days (range 46 to 81 days). The complete RR was 92% (95% confidence interval, 55%-100%). CONCLUSIONS The addition of weekly topotecan to cisplatin at this dose and schedule during pelvic irradiation for locally advanced cervical cancer appears to be feasible. Based on this primary treatment data and the activity of cisplatin-topotecan in the recurrent disease setting, phase II and III studies of this combination are warranted.

A randomized, controlled, double-blind study of light emitting diode photomodulation for the prevention of radiation dermatitis in patients with breast cancer

BACKGROUND AND OBJECTIVES Radiation dermatitis occurs in a majority of patients with breast cancer who receive radiation therapy (RT), causes significant pain, and may necessitate treatment delay. Light emitting diode (LED) photomodulation has been reported to minimize radiation dermatitis. This study sought to further evaluate the efficacy of LED photomodulation in lessening radiation dermatitis. MATERIALS & METHODS After surgery, patients with breast cancer received LED photomodulation or sham treatments in conjunction with three‐dimensional conformal RT. Reactions were evaluated using standardized photographs graded according to National Cancer Institute criteria. RESULTS In the LED treatment group (n=18), no patients had grade 0 reactions, six (33.3%) had grade 1 reactions, 12 (66.7%) had grade 2 reactions, and none had a grade 3 reaction. In the sham treatment group (n=15), one (6.6%) patient had a grade 0 reaction, four (26.7%) had grade 1 reactions, 9 (60.0%) had grade 2 reactions, and one (6.7%) had a grade 3 reaction. Two (11.1%) patients in the LED treatment group and one (6.7%) in the control group had to interrupt treatment. Differences between groups were not statistically significant. CONCLUSION LED photomodulation did not reduce the incidence of radiation‐induced skin reactions or interruptions in therapy. &NA; Funding was provided for this study through the Cutting Edge Research Grant, sponsored by the American Society for Dermatologic Surgery. The GentleWaves LED Select units were loaned for this study by Light BioScience

The University of California, Irvine experience with tomotherapy using the Peacock system ☆

Our institutional experience using the Peacock system for intensity-modulated radiation therapy (IMRT) is summarized. Over 100 patients were treated using this system, which is fitted to a Clinac 600C linac. Both cranial and extracranial lesions have been treated using this modality. Immobilization is achieved either with the Talon system for cranial sites or an Aquaplast cast. Target volumes up to 500 cm3 have been treated. Multiple lesions (up to 3) were treated in one setup. The range of dose/fractionation schemes used was 15 Gy/1 fx (radiosurgical treatment) - 80 Gy/40 fx. Dose validation studies were carried out using film and ion chamber dosimetry in a specially designed phantom. Optimal dose distributions were attainable using inverse treatment planning for IMRT delivery. These were found to encompass the target volumes accurately using dose validation phantom studies. Immobilization methods used were accurate to within 1 mm, as evidenced by daily portal films. IMRT using the Peacock system offers the advantage of delivery of conformal therapy to high doses safely and accurately. This provides the opportunity for dose escalation studies, retreatment of previously treated tumors, as well as treating multiple targets in one setup. The system may be fitted to a conventional linac without major modifications.

The dosimetric impact of image guided radiation therapy by intratumoral fiducial markers

PURPOSE Pancreatic fiducials have proven superior over other isocenter localization surrogates, including anatomical landmarks and intratumoral or adjacent stents. The more clinically relevant dosimetric impact of image guided radiation therapy (IGRT) using intratumoral fiducial markers versus bony anatomy has not yet been described and is therefore the focus of the current study. METHODS AND MATERIALS Using daily orthogonal kV or cone beam computed tomography (CBCT) images and positional and dosimetric data were analyzed for 12 consecutive patients treated with fiducial based IGRT and volumetric modulated arc therapy to the intact pancreas. The shifts from fiducial to bone (ΔFid-Bone) required to realign the daily fiducial-matched pretreatment images (kV, CBCTs) to the planning computed tomography (CT) using bony anatomic landmarks were recorded. The isocenter was then shifted by (ΔFid-Bone) for 5 evenly spaced treatments, and the dosimetric impact of ΔFid-Bone was calculated for planning target volume coverage (PTV50.4 and PTV47.9) and organs at risk (liver, kidney, and stomach/duodenum). RESULTS The ΔFid-Bone were greatest in the superoinferior direction (ΔFid-Bone anteroposterior, 2.7 ± 3.0; left-right, 2.8 ± 2.8; superoinferior, 6.3 ± 7.9 mm; mean ± standard deviation; P = .03). PTV50.4 coverage was reduced by 13% (fiducial plan 95 ± 2.0 vs bone plan 82 ± 12%; P = .005; range, 5%-52%; >5% loss in all; and >10% loss in 42% of patients), and to a lesser degree for PTV47.9 (difference, -8%; range, 1%-30%; fiducial plan 100 ± 0.3% vs bone plan 92 ± 7.6%; P = .003; with reductions of >5% in 66% and >10% in 33% of patients). The dosimetric impact of ΔFid-Bone on the organs at risk was not significant. Positional shifts for kV- and CBCT-based realignments were nearly identical. CONCLUSION Compared with matching by fiducial markers, IGRT matched by bony anatomy substantially reduces the PTV50.4 and PTV47.9 coverage, supporting the use of intratumoral pancreatic markers for improved targeting in IGRT for pancreatic cancer.

SU‐E‐J‐108: Quantitative Analysis of Longitudinal Cognitive Impairment Due to Radiation Therapy Based on Automatic Segmentation of Hippocampus and Subcortical Structure

PURPOSE In this study, we developed a quantitative analysis tool based on patients longitudinal MR images to 1) measure the radiation dose received by each subcortical structure, 2) follow the change of volume and shape of each structure longitudinally. This tool provides a systematic approach to study the radiation therapy (and subsequent chemotherapy) associated with cognitive impairments. METHODS MRI scans of one patient taken before and after radiation therapy are demonstrated in this study. 3D Conformal radiation therapy was performed on RapidArc™. An open source MRI analysis tool, FMRIBs Integrated Registration and Segmentation Tool (FIRST), was used for segmentation. The images are registered to a standard template with expert-defined labeling for all sub-cortical structures, and the labeling of each structure is mapped back to the individual MRI space for segmentation. After the segmentation, the radiation dose map was coregistered to the MRI space to calculate the dose received by each structure. RESULTS For the structure that is contained within the radiation zone, we can calculate the total dose based on the volumetric distribution of radiation dose. For the structure that is outside the radiation field, we can calculate the distance from the radiation zone. We have demonstrated in this work that the analysis can be done for all segmented sub-cortical structures. The change of volume before and after radiation treatment can be analyzed, and the results can be correlated with the change of cognitive performance over time. CONCLUSIONS We presented an automated tool for efficient, quantitative and user-independent measurements of radiation dose in subcortical structures. The obtained results can be correlated with the cognitive test score and the clinical outcome to evaluate radiation and the subsequent chemotherapy induced changes in brain structures and functions.