Matthew C. Biagioli

Radiation Therapy and Esophageal Cancer

BACKGROUND Squamous cell carcinoma and adenocarcinoma account for more than 90% of all esophageal cancer cases. Although the incidence of squamous cell carcinoma has declined, the incidence of adenocarcinoma has risen due to increases in obesity and gastroesophageal reflux disease. METHODS The authors examine the role of radiation therapy alone (external beam and brachytherapy) for the management of esophageal cancer or combined with other modalities. The impact on staging and appropriate stratification of patients referred for curative vs palliative intent with modalities is reviewed. The authors also explore the role of emerging radiation technologies. RESULTS Current data show that neoadjuvant chemoradiotherapy followed by surgical resection is the accepted standard of care, with 3-year overall survival rates ranging from 30% to 60%. The benefit of adjuvant radiation therapy is limited to patients with node-positive cancer. The survival benefit of surgical resection after chemoradiotherapy remains controversial. External beam radiation therapy alone results in few long-term survivors and is considered palliative at best. Radiation dose-escalation has failed to improve local control or survival. Brachytherapy can provide better long-term palliation of dysphagia than metal stent placement. Although three-dimensional conformal treatment planning is the accepted standard, the roles of IMRT and proton therapy are evolving and potentially reduce adverse events due to better sparing of normal tissue. CONCLUSIONS Future directions will evaluate the benefit of induction chemotherapy followed by chemoradiotherapy, the role of surgery in locally advanced disease, and the identification of responders prior to treatment based on microarray analysis.

Stability of endoscopic ultrasound-guided fiducial marker placement for esophageal cancer target delineation and image-guided radiation therapy

PURPOSE Fiducial markers have been integrated into the management of multiple malignancies to guide more precise delivery of radiation therapy (RT). Fiducials placed at the margins of esophageal tumors are potentially useful to facilitate both RT target delineation and image-guided RT (IGRT). In this study, we report on the stability of endoscopic ultrasound (EUS)-guided fiducial placement for esophageal cancers and utilization for radiation treatment planning and IGRT. METHODS An institutional review board-approved database was queried for patients treated for esophageal cancer with chemoradiotherapy (CRT). Patients included in the analysis had a diagnosis of esophageal cancer, were referred for treatment with CRT, and had fiducials placed under EUS guidance. Images acquired at time of radiation treatment planning, daily IGRT imaging, post-treatment restaging, and surveillance scans were analyzed to determine the stability of implanted markers. RESULTS We identified 60 patients who underwent EUS-guided fiducial marker placement near the margins of their esophageal tumors in preparation for RT treatment planning. A total of 105 fiducial markers were placed. At time of CT simulation, 99 markers were visualized. Fifty-seven patients had post-treatment imaging available for review. Of the 100 implanted fiducials in these 57 patients, 94 (94%) were visible at time of RT simulation. Eighty-eight (88%) fiducials were still present post-treatment imaging at a median of 107 days (range, 33-471 days) after implantation. CONCLUSIONS EUS-guided fiducial marker placement for esophageal cancer aids in target delineation for radiation planning and daily IGRT. Fiducial stability is reproducible and facilitates conformal treatment with image-guided RT techniques.

Primary bladder preservation treatment for urothelial bladder cancer.

BACKGROUND Significant advancements have occurred in surgical procedures and chemoradiation therapy for bladder preservation. METHODS This review addresses primary treatment options for bladder cancer, including an overview of bladder-sparing strategies. RESULTS Surgical series demonstrate that highly selected patients with cT2N0M0 urothelial bladder cancers can be managed with partial cystectomy and bilateral pelvic lymphadenectomy. For patients with cT2N0M0 to cT4aN0M0 urothelial bladder cancers, neoadjuvant chemotherapy followed by radical cystectomy or maximal transurethral resection of the bladder tumor (TURBT) followed by chemoradiation therapy results in equivalent survival rates. However, each treatment option has a different impact on quality of life. Current chemoradiation therapy trials are evaluating novel approaches to improve outcomes. CONCLUSIONS Maximal TURBT followed by chemoradiation therapy demonstrated equivalent survival with radical cystectomy while preserving bladder function in the majority of patients. Future efforts will be directed toward improving survival and quality of life.

A dosimetric study of polyethylene glycol hydrogel in 200 prostate cancer patients treated with high-dose rate brachytherapy ± intensity modulated radiation therapy

BACKGROUND AND PURPOSE We sought to analyze the effect of polyethylene glycol (PEG) hydrogel on rectal doses in prostate cancer patients undergoing radiotherapy. MATERIALS AND METHODS Between July 2009 and April 2013, we treated 200 clinically localized prostate cancer patients with high-dose rate (HDR) brachytherapy±intensity modulated radiation therapy. Half of the patients received a transrectal ultrasound (TRUS)-guided transperineal injection of 10mL PEG hydrogel (DuraSeal™ Spinal Sealant System; Covidien, Mansfield, MA) in their anterior perirectal fat immediately prior to the first HDR brachytherapy treatment and 5mL PEG hydrogel prior to the second HDR brachytherapy treatment. Prostate, rectal, and bladder doses and prostate-rectal distances were calculated based upon treatment planning CT scans. RESULTS There was a success rate of 100% (100/100) with PEG hydrogel implantation. PEG hydrogel significantly increased the prostate-rectal separation (mean±SD, 12±4mm with gel vs. 4±2mm without gel, p<0.001) and significantly decreased the mean rectal D2 mL (47±9% with gel vs. 60±8% without gel, p<0.001). Gel decreased rectal doses regardless of body mass index (BMI). CONCLUSIONS PEG hydrogel temporarily displaced the rectum away from the prostate by an average of 12mm and led to a significant reduction in rectal radiation doses, regardless of BMI.

A dosimetric comparison of volumetric modulated arc therapy with step-and-shoot intensity modulated radiation therapy for prostate cancer

PURPOSE To compare variable dose-rate volumetric modulated arc therapy (VMAT) with 7-field, step-and-shoot intensity modulated radiation therapy (IMRT) in prostate cancer patients treated with a consistent planning target volume (PTV) to a uniform total radiation therapy dose. METHODS AND MATERIALS We studied 32 patients who received 8100 cGy in 45 daily fractions to their prostate and proximal 1 cm of the seminal vesicles using variable dose rate VMAT (n = 22) or 7-field, step-and-shoot IMRT (n = 10) for intermediate-risk or high-risk prostate cancer between July 2010 and April 2013. In 90% of patients, VMAT was delivered with 2 arcs. To have an unbiased comparison of plan quality, patients who were treated with VMAT were also planned with IMRT and vice versa. Each patient served as his own control for the comparison. RESULTS VMAT reduced median radiation beam-on time from 4.3 to 3.4 minutes (P = .03). There was no statistically significant difference in PTV volumes between the VMAT and step-and-shoot IMRT groups (P = .76). VMAT dose distributions were more homogeneous (P = .003). There was no difference between groups with regard to rectal V60, V65, V70, V75, bladder V65, V70, V75, V80, or femoral heads V33. CONCLUSIONS Two-arc VMAT resulted in shorter beam-on times and more homogenous dose distributions than 7-field, step-and-shoot IMRT for prostate cancer. With decreased beam-on time, the intrafraction motion during irradiation is reduced, thus improving confidence that the delivered dose distribution agrees with the plan.

Radiation therapy for rectal cancer: current status and future directions.

BACKGROUND Treatment for rectal cancer has evolved over the past 70 years from surgery alone to the selective use of trimodality therapy for high-risk patients. Radiotherapy (RT) has improved the potential for tumor downstaging, thus enhancing sphincter preservation and local control. METHODS This article reviews the evolution of strategies that incorporate pelvic RT, intraoperative RT, and high-dose-rate endorectal brachytherapy (HDRBT). By tracing the arc of the pendulum that has swung from postoperative RT to preoperative RT, we address the current standard of care and explore the potential of novel radiation techniques and radiosensitizing agents to improve outcomes. RESULTS With randomized trial data confirming that preoperative RT in addition to chemotherapy improves local control and decreases acute and late morbidity, neoadjuvant programs have now demonstrated the prognostic significance of downstaging as well. Patients with tumors that have a good response to preoperative treatment have superior survival. CONCLUSIONS Future studies will determine the optimal regimen to enhance the pathologic complete or near complete response rates for locally advanced disease. Advances in radiation technology are being investigated to determine whether efficacy can be increased and toxicity decreased so that more aggressive chemotherapeutic agents can be combined. With the growing improvements in combined modality therapy, a future of better rectal cancer outcomes looms brighter than ever before.

Emerging Technologies in Prostate Cancer Radiation Therapy: Improving the Therapeutic Window

BACKGROUND Radiation therapy is a standard of care in the treatment of prostate cancer. Relatively recent advances in technologies in the delivery of radiation therapy are altering our current approach to treatment of prostate cancer. METHODS This review discusses the results of retrospective, prospective, and randomized clinical trials that have evaluated clinical outcomes in prostate cancer treated with newer radiation therapy technologies. RESULTS Randomized trials have demonstrated that higher doses of radiation therapy improve clinical outcomes but with increased toxicity to normal tissue. The introduction of more conformal radiation therapy techniques such as intensity-modulated radiation therapy, proton therapy, stereotactic body radiotherapy, and brachytherapy have allowed for further dose escalation with simultaneous reduction in toxicity. However, use of more conformal treatments requires a better understanding of prostate motion and the ability to track prostate movements in real time. CONCLUSIONS Technological advancements have improved radiation dose delivery to the prostate and have reduced normal tissue toxicity. Randomized trials are warranted to ultimately evaluate clinical benefit and outcomes.

Intravesical Lipiodol Injection Technique for Image-guided Radiation Therapy for Bladder Cancer

INTRODUCTION To describe the technique of injecting Lipiodol in the submucosa of the urinary bladder wall as a novel modality to improve localization of muscle-invasive bladder tumors before image-guided radiation therapy. TECHNICAL CONSIDERATIONS Eight patients underwent submucosal Lipiodol injections at transurethral bladder tumor reresection. A rigid cystoscope with a working port was used to inject Lipiodol into bladder submucosa circumferentially around the tumor bed (2-3 mm from margin of resection). Approximately 20-30 injections were used to demarcate the tumor bed for external beam radiation therapy, which was used as part of a bladder-sparing approach. All patients were diagnosed with clinically localized, high-grade, muscle-invasive carcinoma and were deemed nonsurgical candidates or were unwilling to undergo radical cystectomy. Five of the 8 patients received radiation at our institution. Lipiodol injections (95%) were visible on treatment planning computed tomographic scans and kilovoltage portal images throughout the 7-week course of image-guided radiation therapy. In 2 of 5 patients, the tumor bed based on Lipiodol extended outside a planning target volume that would have been treated with radiation therapy based on cystoscopy reports and computed tomographic scans without Lipiodol. There were no adverse events or treatment-related toxicities secondary to Lipiodol injection. CONCLUSION Intravesical Lipiodol injection is an easy-to-perform technique that is safe and effective. Lipiodol serves as a fiducial marker that improves tumor bed localization for radiation therapy, thereby reducing the likelihood of missing the tumor.

Accelerated Partial Breast Irradiation: Potential Roles Following Breast-Conserving Surgery

BACKGROUND Multiple randomized trials comparing mastectomy to lumpectomy and whole breast irradiation (WBI) have shown equivalent survival outcomes in early-stage breast cancer. WBI requires a treatment course of several weeks, which has resulted in limited access to breast-conserving therapy in certain populations. A shorter accelerated course of partial breast irradiation (APBI) has been investigated recently. METHODS This article reviews the current medical literature, including randomized trials and prospective institutional studies of APBI and the current recommendations regarding the use of this emerging technique. RESULTS Several APBI techniques have been developed, including brachytherapy and external beam methods. The longest follow-up data are available for multicatheter interstitial brachytherapy, a technique that is not commonly used. Other methods, including balloon brachytherapy and external beam three-dimensional conformal techniques, have limited follow-up that shows similar local control rates to whole breast irradiation in highly selected patients. Guidelines for the appropriate use of APBI have been published. CONCLUSIONS While APBI may increase access to breast conservation therapy for some women with early-stage breast cancer, follow-up data demonstrating the efficacy of this relatively new treatment approach are limited. Therefore, strict evidence-based selection criteria should be applied when evaluating patients who may be appropriate for APBI.

Dose Reduction Study in Vaginal Balloon Packing Filled With Contrast for HDR Brachytherapy Treatment

PURPOSE Vaginal balloon packing is a means to displace organs at risk during high dose rate brachytherapy of the uterine cervix. We tested the hypothesis that contrast-filled vaginal balloon packing reduces radiation dose to organs at risk, such as the bladder and rectum, in comparison to water- or air-filled balloons. METHODS AND MATERIALS In a phantom study, semispherical vaginal packing balloons were filled with air, saline solution, and contrast agents. A high dose rate iridium-192 source was placed on the anterior surface of the balloon, and the diode detector was placed on the posterior surface. Dose ratios were taken with each material in the balloon. Monte Carlo (MC) simulations, by use of the MC computer program DOSXYZnrc, were performed to study dose reduction vs. balloon size and contrast material, including commercially available iodine- and gadolinium-based contrast agents. RESULTS Measured dose ratios on the phantom with the balloon radius of 3.4 cm were 0.922 ± 0.002 for contrast/saline solution and 0.808 ± 0.001 for contrast/air. The corresponding ratios by MC simulations were 0.895 ± 0.010 and 0.781 ± 0.010. The iodine concentration in the contrast was 23.3% by weight. The dose reduction of contrast-filled balloon ranges from 6% to 15% compared with water-filled balloon and 11% to 26% compared with air-filled balloon, with a balloon size range between 1.4 and 3.8 cm, and iodine concentration in contrast of 24.9%. The dose reduction was proportional to the contrast agent concentration. The gadolinium-based contrast agents showed less dose reduction because of much lower concentrations in their solutions. CONCLUSIONS The dose to the posterior wall of the bladder and the anterior wall of the rectum can be reduced if the vaginal balloon is filled with contrast agent in comparison to vaginal balloons filled with saline solution or air.