M. Lock

Systematic review of dose―volume parameters in the prediction of esophagitis in thoracic radiotherapy

PURPOSE With dose escalation and increasing use of concurrent chemoradiotherapy, radiation esophagitis (RE) remains a common treatment-limiting acute side effect in the treatment of thoracic malignancies. The advent of 3DCT planning has enabled investigators to study esophageal dose-volume histogram (DVH) parameters as predictors of RE. The purpose of this study was to assess published dosimetric parameters and toxicity data systematically in order to define reproducible predictors of RE, both for potential clinical use, and to provide recommendations for future research in the field. MATERIALS AND METHODS We performed a systematic literature review of published studies addressing RE in the treatment of lung cancer and thymoma. Our search strategy included a variety of electronic medical databases, textbooks and bibliographies. Both prospective and retrospective clinical studies were included. Information relating to the relationship among measured dosimetric parameters, patient demographics, tumor characteristics, chemotherapy and RE was extracted and analyzed. RESULTS Eighteen published studies were suitable for analysis. Eleven of these assessed acute RE, while the remainder assessed both acute and chronic RE together. Heterogeneity of esophageal contouring practices, individual differences in information reporting and variability of RE outcome definitions were assessed. Well-described clinical and logistic modeling directly related V(35Gy), V(60Gy) and SA(55Gy) to clinically significant RE. CONCLUSIONS Several reproducible dosimetric parameters exist in the literature, and these may be potentially relevant in the prediction of RE in the radiotherapy of thoracic malignancies. Further clarification of the predictive relationship between such standardized dosimetric parameters and observed RE outcomes is essential to develop efficient radiation treatment planning in locally advanced NSCLC in the modern concurrent chemotherapy and image-guided IMRT era.

Phase I Trial of Simultaneous In-Field Boost With Helical Tomotherapy for Patients With One to Three Brain Metastases

PURPOSE Stereotactic radiosurgery is an alternative to surgical resection for selected intracranial lesions. Integrated image-guided intensity-modulated-capable radiotherapy platforms such as helical tomotherapy (HT) could potentially replace traditional radiosurgery apparatus. The present studys objective was to determine the maximally tolerated dose of a simultaneous in-field boost integrated with whole brain radiotherapy for palliative treatment of patients with one to three brain metastases using HT. METHODS AND MATERIALS The inclusion/exclusion criteria and endpoints were consistent with the Radiation Therapy Oncology Group 9508 radiosurgery trial. The cohorts were constructed with a 3 + 3 design; however, additional patients were enrolled in the lower dose tolerable cohorts during the toxicity assessment periods. Whole brain radiotherapy (30 Gy in 10 fractions) was delivered with a 5-30-Gy (total lesion dose of 35-60 Gy in 10 fractions) simultaneous in-field boost delivered to the brain metastases. The maximally tolerated dose was determined by the frequency of neurologic Grade 3-5 National Cancer Institute Common Toxicity Criteria, version 3.0, dose-limiting toxicity events within each Phase I cohort. RESULTS A total of 48 patients received treatment in the 35-Gy (n = 3), 40-Gy (n = 16), 50-Gy (n = 15), 55-Gy (n = 8), and 60-Gy (n = 6) cohorts. No patients experienced dose-limiting toxicity events in any of the trial cohorts. The 3-month RECIST assessments available for 32 of the 48 patients demonstrated a complete response in 2, a partial response in 16, stable disease in 6, and progressive disease in 8 patients. CONCLUSION The delivery of 60 Gy in 10 fractions to one to three brain metastases synchronously with 30 Gy whole brain radiotherapy was achieved without dose-limiting central nervous system toxicity as assessed 3 months after treatment. This approach is being tested in a Phase II efficacy trial.

Automated IMRT planning with regional optimization using planning scripts

Intensity‐modulated radiation therapy (IMRT) has become a standard technique in radiation therapy for treating different types of cancers. Various class solutions have been developed for simple cases (e.g., localized prostate, whole breast) to generate IMRT plans efficiently. However, for more complex cases (e.g., head and neck, pelvic nodes), it can be time‐consuming for a planner to generate optimized IMRT plans. To generate optimal plans in these more complex cases which generally have multiple target volumes and organs at risk, it is often required to have additional IMRT optimization structures such as dose limiting ring structures, adjust beam geometry, select inverse planning objectives and associated weights, and additional IMRT objectives to reduce cold and hot spots in the dose distribution. These parameters are generally manually adjusted with a repeated trial and error approach during the optimization process. To improve IMRT planning efficiency in these more complex cases, an iterative method that incorporates some of these adjustment processes automatically in a planning script is designed, implemented, and validated. In particular, regional optimization has been implemented in an iterative way to reduce various hot or cold spots during the optimization process that begins with defining and automatic segmentation of hot and cold spots, introducing new objectives and their relative weights into inverse planning, and turn this into an iterative process with termination criteria. The method has been applied to three clinical sites: prostate with pelvic nodes, head and neck, and anal canal cancers, and has shown to reduce IMRT planning time significantly for clinical applications with improved plan quality. The IMRT planning scripts have been used for more than 500 clinical cases. PACS numbers: 87.55.D, 87.55.de

A Phase II Trial of Arc-Based Hypofractionated Intensity-Modulated Radiotherapy in Localized Prostate Cancer

PURPOSE To evaluate acute and late genitourinary (GU) and gastrointestinal (GI) toxicity and biochemical control of hypofractionated, image-guided (fiducial markers or ultrasound guidance), simplified intensity-modulated arc therapy for localized prostate cancer. METHODS AND MATERIALS This Phase II prospective clinical trial for T1a-2cNXM0 prostate cancer enrolled 66 patients who received 63.2 Gy in 20 fractions over 4 weeks. Fiducial markers were used for image guidance in 30 patients and daily ultrasound for the remainder. Toxicity was scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. RESULTS Median follow-up was 36 months. Acute Phase Grade 2 and 3 toxicity was 34% and 9% for GU vs. 25% and 10% for GI symptoms. One Grade 4 acute GI toxicity occurred in a patient with unrecognized Crohns disease. Late Grade 2 and 3 toxicity for GU was 14% and 5%, and GI toxicity was 25% and 3%. One late GI Grade 4 toxicity was observed in a patient with significant comorbidities (anticoagulation, vascular disease). Acute GI toxicity ≥ Grade 2 was shown to be a predictor for late toxicity Grade ≥ 2 (p < 0.001). The biochemical disease-free survival at 3 years was 95%. CONCLUSIONS Hypofractionated simplified intensity-modulated arc therapy radiotherapy given as 63.2 Gy in 20 fractions demonstrated promising biochemical control rates; however, higher rates of acute Grade 3 GU and GI toxicity and higher late Grade 2 GU and GI toxicity were noted. Ongoing randomized controlled trials should ultimately clarify issues regarding patient selection and the true rate of severe toxicity that can be directly attributed to hypofractionated radiotherapy.

Impact of urethrography on geometric uncertainty in prostate cancer radiotherapy

Results: The average systematic displacement (and standard deviation) of the prostate on treatment as measured from the position at the time of simulation/urethrography was 0.02cm (0.24), 0.00cm (0.39), and 0.32cm (0.38) in the x (left:, right:), y(anterior:, posterior:) and z(cephalad:, caudad:) directions, respectively (Figure). The average threedimensional vector of 0.32cm was in an anterior-cephalad direction; consistent with the urethrography induced prostate motion noted by Malone (1). Using our measurements and the Monte Carlo geometric error equations from van Herk (2), a required planning target margin (PTV) of 0.87cm was needed in order to give 90% of patients an equivalent uniform dose (EUD) of at least 98% of the prescription dose. For coverage of the prostate for 95% of the treatment fractions, PTV margins of 1.0cm and 0.6cm were necessary with and without the inclusion of the systematic error attributed to the urethrogram. Conclusions: Using a combination of implanted markers and weekly CT scans we detected a systematic shift of the prostate apex and centre of mass superiorly/cephalad at the time of simulation/urethrography compared to during treatment. While our current 1cm PTV margins are sufficient to compensate for geometric uncertainties including this shift, reduced margins in the context of dose or fraction escalation may require methods other than urethrography to help localize the apex of the prostate.

Reducing Patient Waiting Times for Radiation Therapy and Improving the Treatment Planning Process: a Discrete-event Simulation Model (Radiation Treatment Planning)

AIMS We analysed the radiotherapy planning process at the London Regional Cancer Program to determine the bottlenecks and to quantify the effect of specific resource levels with the goal of reducing waiting times. MATERIALS AND METHODS We developed a discrete-event simulation model of a patients journey from the point of referral to a radiation oncologist to the start of radiotherapy, considering the sequential steps and resources of the treatment planning process. We measured the effect of several resource changes on the ready-to-treat to treatment (RTTT) waiting time and on the percentage treated within a 14 calendar day target. RESULTS Increasing the number of dosimetrists by one reduced the mean RTTT by 6.55%, leading to 84.92% of patients being treated within the 14 calendar day target. Adding one more oncologist decreased the mean RTTT from 10.83 to 10.55 days, whereas a 15% increase in arriving patients increased the waiting time by 22.53%. The model was relatively robust to the changes in quantity of other resources. CONCLUSIONS Our model identified sensitive and non-sensitive system parameters. A similar approach could be applied by other cancer programmes, using their respective data and individualised adjustments, which may be beneficial in making the most effective use of limited resources.