Albert Mesa

Dose distributions using kilovoltage x-rays and dose enhancement from iodine contrast agents

In x-ray phototherapy of brain tumours, the tumour is loaded with iodine and exposed to kilovoltage x-rays. Due to the high photoelectric cross sections of iodine, substantial photoelectric interactions occur. The flux of photoelectrons, characteristic x-rays and Auger electrons produce a localized dose enhancement. A modified computed tomography scanner, CTRx, can be used both for tumour localization and delivery of the dose enhancement therapy. Monte Carlo methods were employed to simulate the treatment of iodinated brain tumours with a CTRx. The calculated results reveal the effect of tumour iodine concentration on dose distribution, the degree of skull bone sparing with the application of multiple arcs, and the homogeneity of tumour dose distribution versus iodine concentration. A comparison with 10 MV stereotactic radiosurgery treatment shows the potential of CTRx treatment relative to conventional treatment modalities.

First radiotherapy of human metastatic brain tumors delivered by a computerized tomography scanner (CTRx)

PURPOSE This Phase I study was designed to evaluate the computed tomography (CT) scanner as a device for radiation therapy of human brain tumors (CTRx). This first use in humans of a modified CT for treatment was founded on extensive research experience with canine tumors. An additional objective was to increase the therapeutic radiation dose to tumors compared to normal tissue by concentration of infused contrast material in tumors, an effect available at diagnostic x-ray energies but not at megavoltage energies. METHODS AND MATERIALS A small metastatic brain tumor in each of eight patients received 3-5-weekly fractions of 5 Gy equivalent per fraction from a CT scanner modified to deliver radiation therapy. In each patient, one additional tumor, lying completely outside the volume treated by CTRx, served as a control. The tumor receiving CTRx was treated after infusion of iodinated x-ray contrast media (CM) for dose enhancement. Many of these patients also received conventional 40 Gy whole brain radiation, before, during, or after CTRx treatment. RESULTS None of the patients showed adverse reactions to the CM or necrosis of the normal brain from the CTRx boost radiation. Monte Carlo calculations of the radiation dose distributions in a model tumor showed that the CTRx irradiation of tumors carrying 10 mg or more of iodine per gram of tumor was as good or better than the dose distribution from conventional 10-MV X-rays. The treated tumor in two of the patients vanished after four treatments, whereas a control tumor in one patient remained constant and grew 4-fold in another patient. CONCLUSION The CTRx concept effectively combines a modified CT scanner as a diagnostic device, as a simulator dedicated to radiotherapy, and as a treatment machine. Thus, CTRx could be very useful for radiation oncologists in controlling CM-enhanced and other small brain tumors.

Cross-Linked Hyaluronan Gel Reduces the Acute Rectal Toxicity of Radiotherapy for Prostate Cancer

PURPOSE To prospectively analyze whether cross-linked hyaluronan gel reduces the mean rectal dose and acute rectal toxicity of radiotherapy for prostate cancer. METHODS AND MATERIALS Between September 2008 and March 2009, we transperitoneally injected 9 mL of cross-linked hyaluronan gel (Hylaform; Genzyme Corporation, Cambridge, MA) into the anterior perirectal fat of 10 early-stage prostate cancer patients to increase the separation between the prostate and rectum by 8 to 18 mm at the start of radiotherapy. Patients then underwent high-dose rate brachytherapy to 2,200 cGy followed by intensity-modulated radiation therapy to 5,040 cGy. We assessed acute rectal toxicity using the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 grading scheme. RESULTS Median follow-up was 3 months. The anteroposterior dimensions of Hylaform at the start and end of radiotherapy were 13 +/- 3mm (mean +/- SD) and 10 +/- 4mm, respectively. At the start of intensity-modulated radiation therapy, daily mean rectal doses were 73 +/- 13 cGy with Hylaform vs. 106 +/- 20 cGy without Hylaform (p = 0.005). There was a 0% incidence of National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 Grade 1, 2, or 3 acute diarrhea in 10 patients who received Hylaform vs. a 29.7% incidence (n = 71) in 239 historical controls who did not receive Hylaform (p = 0.04). CONCLUSIONS By increasing the separation between the prostate and rectum, Hylaform decreased the mean rectal dose. This led to a significant reduction in the acute rectal toxicity of radiotherapy for prostate cancer.

Cross-linked hyaluronan gel improves the quality of life of prostate cancer patients undergoing radiotherapy

PURPOSE To test the hypothesis that cross-linked hyaluronan gel (Hylaform) does not affect the quality of life (QOL) of prostate cancer patients undergoing radiotherapy. METHODS AND MATERIALS Thirty-five patients with early stage prostate cancer underwent high-dose-rate brachytherapy to 2200 cGy and intensity modulated radiation therapy to 5040 cGy on a prospective study. Thirty patients received a single transperineal injection of 9-mL Hylaform between the prostate and rectum under transrectal ultrasound guidance immediately before the start of radiotherapy. Hylaform increased the separation between the prostate and rectum by 6-19 mm (median, 13 mm) at the start of radiotherapy. Five patients did not receive Hylaform and served as controls. We assessed gastrointestinal-related QOL using Expanded Prostate Cancer Index Composite Bowel Bother scores immediately before the start of and during the last week of radiotherapy. RESULTS At the beginning of intensity modulated radiation therapy, daily mean rectal doses were 74±8 cGy (mean±standard deviation) and 105±25 cGy (mean±standard deviation) with vs. without Hylaform, respectively (p=0.01). Expanded Prostate Cancer Index Composite Bowel Bother scores decreased by 0±3 (mean±standard deviation) and 11±14 (mean±standard deviation) in patients who did and did not receive Hylaform, respectively (p=0.03). CONCLUSIONS Hylaform increased the separation between the prostate and rectum and decreased the mean rectal dose, thereby improving the gastrointestinal-related acute QOL of prostate cancer patients undergoing radiotherapy. Patients will be followed up long term to determine if the improvement in acute QOL also translates into an improvement in late QOL.

A Prospective Study of Intrafraction Prostate Motion in the Prone vs. Supine Position

PURPOSE To prospectively analyze prostate intrafraction motion in the prone vs. supine position and to assess patient satisfaction with these two positions. METHODS AND MATERIALS Fifteen prostate cancer patients underwent implantation of five fiducial gold seeds in their prostate for localization. Patients were treated with high-dose-rate brachytherapy to 2,200 cGy followed by intensity-modulated radiation therapy (IMRT) to 5,040 cGy. Patients underwent computed tomography simulation and IMRT in the prone position. For the first five IMRT treatments, an electronic portal imaging system was used to acquire anteroposterior (AP) and lateral images pretreatment and posttreatment. We then repositioned each patient supine and repeated the process, resulting in 600 images. RESULTS Mean +/- standard deviation intrafraction prostate motion was 2.1 +/- 1.2 mm and 1.7 +/- 1.4 mm (AP, p = 0.47), 2.2 +/- 2.0 mm and 1.6 +/- 1.8 mm (superoinferior, p = 0.16), and 1.0 +/- 1.2 mm and 0.6 +/- 0.9 mm (left-right, p = 0.03) in the prone and supine positions, respectively. Eighty percent of patients stated that they were more comfortable in the supine position (p = 0.02). CONCLUSIONS Prone and supine positions resulted in a similar magnitude of AP and superoinferior intrafraction prostate motion (2 mm). Because there was no significant difference in the magnitude of AP and superoinferior prostate motion prone vs. supine and patients were more comfortable in the supine position, patients now undergo IMRT to the prostate and seminal vesicles at our center in the supine position.

Results With Accelerated Partial Breast Irradiation in Terms of Estrogen Receptor, Progesterone Receptor, and Human Growth Factor Receptor 2 Status

PURPOSE To report our results with accelerated partial breast irradiation (APBI) in terms of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2/neu) status. METHODS AND MATERIALS Between February 2003 and June 2009, 209 women with early-stage breast carcinomas were treated with APBI using multicatheter, MammoSite, or Contura brachytherapy to 34 Gy in 10 fractions twice daily over 5-7 days. Three patient groups were defined by receptor status: Group 1: ER or PR (+) and HER-2/neu (-) (n = 180), Group 2: ER and PR (-) and HER-2/neu (+) (n = 10), and Group 3: ER, PR, and HER-2/neu (-) (triple negative breast cancer, n = 19). Median follow-up was 22 months. RESULTS Group 3 patients had significantly higher Scarff-Bloom-Richardson scores (p < 0.001). The 3-year ipsilateral breast tumor control rates for Groups 1, 2, and 3 were 99%, 100%, and 100%, respectively (p = 0.15). Group 3 patients tended to experience relapse in distant sites earlier than did non-Group 3 patients. The 3-year relapse-free survival rates for Groups 1, 2, and 3 were 100%, 100%, and 81%, respectively (p = 0.046). The 3-year cause-specific and overall survival rates for Groups 1, 2, and 3 were 100%, 100%, and 89%, respectively (p = 0.002). CONCLUSIONS Triple negative breast cancer patients typically have high-grade tumors with significantly worse relapse-free, cause-specific, and overall survival. Longer follow-up will help to determine whether these patients also have a higher risk of ipsilateral breast tumor relapse.

Preliminary results in prostate cancer patients treated with high-dose-rate brachytherapy and intensity modulated radiation therapy (IMRT) vs. IMRT alone

PURPOSE To analyze results with high-dose-rate (HDR) brachytherapy and intensity modulated radiation therapy (IMRT) vs. IMRT alone for prostate cancer. METHODS AND MATERIALS Between October 2003 and August 2008, 284 patients with early stage prostate cancer underwent HDR brachytherapy to 2200cGy and IMRT to 5040cGy (n=240) or IMRT alone to 7920-8100cGy (n=44). RESULTS The median followup was 2.2 years. There was no significant difference in terms of the proportions of patients who had diabetes mellitus (p=0.07) or who received hormonal therapy (p=0.75) by radiotherapy technique. The 3-year biochemical disease-free survival rates in low-risk, intermediate-risk, and high-risk patients treated with HDR brachytherapy and IMRT are 100%, 98%, and 93%, respectively. The 3-year biochemical disease-free survival rates in low-risk, intermediate-risk, and high-risk patients treated with IMRT alone are 100%, 100%, and 67%, respectively. There was no significant difference in biochemical disease-free survival or toxicity between treatment groups. The similarity in outcomes between treatment groups remained unchanged when we examined only hormone-naive patients. CONCLUSIONS The HDR brachytherapy and IMRT yielded similar biochemical disease-free survival and toxicity to IMRT alone. As a result, we continue to base treatment on physician and patient preference. Longer followup will help to determine the role of HDR brachytherapy and IMRT in the treatment of early stage prostate cancer, particularly because a number of patients received androgen deprivation therapy and we delivered a higher biologically effective dose with combined modality therapy.

Preliminary results with accelerated partial breast irradiation in high-risk breast cancer patients

PURPOSE To analyze prognostic factors in adequately staged breast cancer patients who were treated with accelerated partial breast irradiation (APBI). METHODS AND MATERIALS Axillary staging was required for invasive carcinomas. Between February 2003 and June 2009, 204 women with early stage breast carcinomas were treated with APBI using multicatheter, MammoSite, or Contura brachytherapy to 34 Gy in 10 fractions 2 times per day. Six patient characteristics were examined for prognostic significance: (1) N stage, (2) estrogen receptor (ER) status, (3) histologic subtype, (4) margin status, (5) age, and (6) tumor size. The median followup was 22 months. RESULTS There were three failures in the ipsilateral breast (all were elsewhere failures), one relapse in the axilla, and seven relapses at any site. The presence of positive axillary node(s) had a significant adverse effect on ipsilateral breast tumor control (p=0.045) and locoregional control (p=0.001). The presence of an ER (-) tumor had a significant adverse effect on relapse-free survival (p=0.04). CONCLUSIONS The patients with positive axillary node(s) were at increased risk for failure elsewhere in the ipsilateral breast or axilla, and the patients with ER (-) tumors were at increased risk for relapse at any site. However, it is unclear whether the pN1 and ER (-) patients would have faired any better if they had received whole breast irradiation rather than APBI. We believe that the patients with positive axillary node(s) or ER (-) tumors should be treated on clinical trials to better define the role of APBI.

Preliminary Results in 173 Breast Cancer Patients Treated with Post-Lumpectomy MammoSite Single-Lumen Brachytherapy or Multi-Catheter Brachytherapy

Abstract:  The objective of this study was to report our single‐institution results with MammoSite and multi‐catheter brachytherapy. Between February 2003 and January 2009, 173 women with unifocal pathological Tis, T1, or T2 (up to 30 mm), N0 or N1 carcinomas of the breast were treated with post‐lumpectomy brachytherapy to 34 Gy in 10 fractions over 5–10 days. We treated 137 patients with MammoSite single‐lumen balloon brachytherapy, and 36 patients with multi‐catheter brachytherapy. Patients with small and/or nonspherical lumpectomy cavities were usually treated with multi‐catheter brachytherapy using 4–12 interstitial catheters. Median follow‐up was 33 months. Three‐year ipsilateral breast tumor control, disease‐free, and overall survival rates for MammoSite brachytherapy were 100%, 100%, and 99%, respectively. Similar rates were obtained with multi‐catheter brachytherapy. Minimum distances from the planning target volume for plan evaluation to a rib were 10 ± 8 mm (mean ± standard deviation) and 8 ± 4 mm (mean ± standard deviation) for MammoSite brachytherapy and multi‐catheter brachytherapy, respectively (p = 0.48). Maximum rib doses were 101 ± 14% (mean ± standard deviation) and 74 ± 10% (mean ± standard deviation) of the prescribed dose for MammoSite brachytherapy and multi‐catheter brachytherapy, respectively (p = 0.001). Multi‐catheter brachytherapy results in more conformal radiation dose delivery and a significantly lower rib dose than MammoSite single‐lumen brachytherapy. Long‐term follow‐up is needed to determine if the delivery of a lower radiation dose to the ribs will translate into a lower incidence of rib pain and fractures.

Three-year outcomes of 324 prostate carcinoma patients treated with combination high-dose-rate brachytherapy and intensity modulated radiation therapy

Background: To report 3-year outcomes of patients treated with combination high-dose-rate (HDR) brachytherapy with intensity modulated radiation therapy (IMRT) for prostate carcinoma. Methods: Between 2002 and 2014, 324 prostate carcinoma patients received combination HDR brachytherapy [Iridium-192 (Ir-192)] and external beam IMRT. A total of 16 Gray (Gy) over 4 fractions was administered with HDR brachytherapy followed by 59.4 Gy over 33 fractions of external beam IMRT. Rates of biochemical control and distant metastasis were recorded along with incidence of late genitourinary (GU) and gastrointestinal (GI) toxicities. Results: Three-year prostate specific antigen (PSA) biochemical control rates for low, intermediate, and high risk patients were 95%, 99%, and 83%, respectively. Three-year incidence of distant metastases for low, intermediate, and high risk patients were 0%, 0%, and 7%, respectively. Three-year incidence of late grade 1, 2, and 3 GU toxicities were 9.0%, 3.0%, and 1.5%, respectively, and the 3-year incidence of grade 1, 2, and 3 GI toxicities were 6%, 2.2% and 0.4%, respectively. Multivariate analysis showed that age (>65), PSA (>10), and Gleason scores (≥8) were predictive of decreased biochemical control. Conclusions: Combination HDR/IMRT for the treatment of clinically localized prostate cancer yields excellent clinical outcomes. High rates of PSA control and low incidence of late GI and GU toxicities are achievable with combination HDR/IMRT treatment for prostate cancer.