Longitudinal assessment of anchored transponder migration following lung stereotactic body radiation therapy.

PURPOSE: To assess the long-term stability of the anchored radiofrequency transponders and compare displacement rates with other commercially available lung fiducial markers. We also sought to describe late toxicity attributable to fiducial implantation or migration. MATERIALS AND METHODS: The transponder cohort was comprised of 17 patients at our institution who enrolled in a multisite prospective clinical trial and underwent bronchoscopic implantation of three anchored transponders into small (2-2.5 mm) airways. We generated a comparison cohort of 34 patients by selecting patients from our institutional lung SBRT database and matching 2:1 based on the lobe containing tumor and proximity to the bronchial tree. Assessment of migration was performed by rigidly registering the most recent follow-up CT scan to the simulation scan, and assessing whether the relative geometry of the fiducial markers had changed by more than 5 mm. Toxicity outcomes of interest were hemoptysis and pneumothorax. RESULTS: The median follow-up of patients in the transponder cohort was 25.3 months and the median follow-up in the comparison cohort was 21.7 months. When assessing the most recent CT, all fiducial markers were within 5 mm of their position at CT simulation in 11 (65%) patients in the transponder group as compared to 23 (68%) in the comparison group (P = 0.28). One case of hemoptysis was identified in the transponder cohort, and bronchoscopy confirmed bleeding from recurrent tumor; no cases of hemoptysis were noted in the comparison cohort. No case of pneumothorax was noted in either group. CONCLUSION: No significant difference in the rates of fiducial marker retention and migration were noted when comparing patients who had anchored transponders placed into small airways and a 2:1 matched cohort of patients who had other commercially available lung fiducial markers placed. In both groups, no late or chronic toxicity appeared to be related to the implanted fiducial markers.

Outcomes with abiraterone acetate in metastatic castration-resistant prostate cancer patients who have poor performance status.

BACKGROUND: Although abiraterone acetate (abiraterone) has proven efficacy in two randomised phase 3 trials in metastatic castration-resistant prostate cancer (mCRPC), patients who had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2 were either excluded or under-represented in these trials. OBJECTIVE: To compare outcomes in ECOG PS 0-1 and ≥2 in mCRPC patients treated with abiraterone. DESIGN, SETTING, AND PARTICIPANTS: Cancer registries from three Canadian centres were used to retrospectively identify mCRPC patients (postdocetaxel and docetaxel-naïve) treated with abiraterone. ECOG PS, clinicopathologic characteristics, prostate-specific antigen (PSA) response, and survival data were collected. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Survival outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazards modelling was used to examine the effect of clinicopathologic characteristics on overall survival (OS) and time to PSA progression. RESULTS AND LIMITATIONS: A total of 519 patients were identified; 61% (n=318) and 39% (n=201) were ECOG PS 0-1 and ≥2, respectively. ECOG PS 0-1 patients were significantly more likely than PS ≥2 patients to achieve a PSA decline ≥50% from baseline (45% vs 32%; p=0.003, Fisher exact test) and had significantly longer median time to PSA progression (5.2 mo vs 4.1 mo; p=0.023), median treatment duration (7.4 mo vs 4.5 mo; p<0.001), and median OS (20.0 mo vs 9.1 mo; p<0.001). On multivariate analysis, ECOG PS was a significant factor for OS (p<0.001), time to PSA progression (p=0.043), and PSA decline (p=0.002). Potential limitations include the retrospective study design and subjective nature of ECOG PS classification. CONCLUSIONS: ECOG PS ≥2 mCRPC patients treated with abiraterone have inferior outcomes compared with ECOG 0-1 patients, especially in regard to OS. These data indicate that early initiation of abiraterone prior to a decline in PS may be warranted. PATIENT SUMMARY: We found that advanced prostate cancer patients who have worse performance status (PS) derive less benefit from abiraterone, indicating that earlier treatment before PS declines could improve outcomes.

A multicentre analysis of abiraterone acetate in Canadian patients with metastatic castration-resistant prostate cancer.

INTRODUCTON: The COU-AA-301 trial showed that abiraterone acetate (abiraterone), an oral cytochrome p450 CYP17 inhibitor, improved survival for men with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel. To better understand the non-clinical trial experience with abiraterone, we undertook a multicentre retrospective analysis of Canadian mCRPC patients treated with abiraterone. METHODS: Consecutive patients with mCRPC who received abiraterone post-docetaxel were identified using centralized pharmacy records. These patients came from 5 Canadian tertiary cancer centres. Patients who received abiraterone for approved indications were included. Demographics, prognostic factors, treatment outcomes and adverse events were abstracted. RESULTS: We included 187 patients who initiated abiraterone between January 2011 and June 2012. The median age at diagnosis and abiraterone start was 65 and 73 years, respectively. Seventy-three (39%) patients had metastatic disease at diagnosis. The Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2 and 3 was noted in 17, 96, 39 and 8 patients, respectively. The median prostate-specific antigen (PSA) at abiraterone start was 132, with a median PSA doubling time of 2.8 months. The median follow-up of patients still on active follow-up was 13 months. The proportion of patients achieving a ≥50% PSA reduction was 64/177 (36%). PSA progression-free survival was 3.5 months (95% confidence interval [CI], 3.0, 4.0). Median overall survival from start of abiraterone was 11 months (95% CI, 8.0, 13) and 38 months (95% CI, 31, 41) from date of mCRPC. Anemia and fatigue were the most commonly reported adverse events. CONCLUSIONS: This study carries the inherent limitations of a retrospective chart review. The outcomes in this series of men treated with abiraterone in a non-trial setting were expected, considering previous clinical trials. Our results, therefore, support the generalizability of the COU-AA-301 study results.

Clinical impact of using the deterministic patient dose calculation algorithm Acuros XB for lung stereotactic body radiation therapy.

PURPOSE: To evaluate the clinical impact of using the deterministic dose calculation algorithm, Acuros XB, for early stage lung cancer patients undergoing stereotactic body radiotherapy (SBRT). MATERIAL AND METHODS: Seventy-seven stage I non-small cell lung cancer patients who underwent lung SBRT from 2008 to 2012 at our center were included in this study. All treatment plans originally calculated by the anisotropic analytical algorithm (AAA) were recalculated using the AAA and Acuros XB algorithms with identical monitor units and beam arrangements. The dose, dose distribution, conformality number (CN) and heterogeneity index (HI) of the target were determined for each plan. A paired matched t-test was used to evaluate the difference between the mean dose, the dose distribution, and the CN and HI for the target. The importance of tumor (volume, location), patient (pulmonary functional, body mass index) and treatment (number of SBRT beams) on the dose distributions obtained from the two algorithms was statistically determined using linear regression analyses. RESULTS: The mean target dose was same for both algorithms. Compared to AAA, a small and significant difference in dose distribution in the target was found for the Acuros XB algorithm, resulting in lower conformity (-2.1%, p < 0.0001) and higher heterogeneity (p < 0.0001) of dose. Single logistic regression identified pulmonary function, number of beams and target location as being correlated with the difference of CN between the two calculations. Multivariate analysis indicated that the patient's pulmonary function (p = 0.0296) was the only predictor for the difference in conformality between the two dose calculation algorithms. CONCLUSIONS: In lung SBRT, the patient's pulmonary function is responsible for the difference in target dose distribution between the Acuros XB and AAA algorithms. The Acuros XB algorithm could be used to advantage in patients with compromised pulmonary function based on its accurate modeling of lung tissue in comparison to AAA.

The impact of undergraduate education in radiation oncology.

Many medical practitioners provide care to patients for whom radiotherapy [radiation oncology (RO)] is a recommended treatment or who have received radiotherapy treatment for cancer. A basic level of understanding about this modality is important to ensure a continuum of good patient care. This study aimed to explore the current teaching practices in RO across medical schools in Canada and understand the perception of RO as a career choice among final-year medical students. Ethics approval and/or consent was obtained from each medical school prior to sending an electronic survey to the Undergraduate Medical Education office and to the final-year medical school class. Only six of the 14 Canadian medical schools participated in the surveys. Four of the 14 refused external surveys. The response rate was 8 % (155/1,917) for all final-year medical students and 17 % (155/897) for students from participating medical schools. Didactic lectures are the primary means of delivering RO knowledge. One in five students reports that they did not receive any RO teaching, and 65 % received <2 h. The level of interest in RO as a career choice (scale of 1-5) was greater in students who received >2 h of RO teaching (2.85 vs. 3.18, p = 0.012) and those that took part in a RO elective (2.86 vs. 3.53, p < 0.001). This study confirms the underrepresentation of RO teaching within the Canadian undergraduate medical curriculum. Interest in this specialty is minimal but does appear to be influenced by exposure to RO teaching. It is important to highlight the limitations of conducting a survey study within the Canadian medical undergraduate system. Steps to conduct such studies in a more seamless fashion are required, in order to assist curriculum development in RO and enhance the understanding of the specialty as a career choice.

Implementation of Lung Stereotactic Ablative Radiotherapy at a Regional Cancer Centre.

BACKGROUND: For patients with inoperable Stage I (T1-T2, N0, M0) non-small-cell lung cancer, stereotactic ablative radiotherapy (SABR), also known as stereotactic body radiation therapy (SBRT), has demonstrated survival outcomes similar to surgery. Lung SABR is a technically challenging means of delivering precise, high-dose radiation to a small tumor volume. At many cancer centres, the widespread use of SABR is impeded by the complexity of the implementation process. This study will aim to provide a detailed guide to the steps involved in delivering lung SABR in a reliable and efficient manner. PROCESS: The execution of this intricate treatment program at our cancer centre required the collaboration of a multidisciplinary team. Input from several professionals within radiation oncology was necessary, including medical physicists, dosimetrists, radiation therapists, nurses, and radiation oncologists. Expert guidelines have been developed which give careful consideration to each step of the process, including 1) reliable and reproducible patient immobilization, 2) a method to account for tumor and organ motion, 3) the use of multiple treatment fields to deliver highly conformal radiation dose with a rapid dose fall off, 4) daily imaging that allows for repositioning from simulation to treatment, 5) accurate and precise dose-calculation algorithms, and 6) a vigorous quality assurance program. Lung SABR was introduced at our centre in 2007 and thus far 92 patients have been treated. There are currently three treatment machines capable of performing this procedure. BENEFITS/CHALLENGES: Patient immobilization through the use of body cushions, accurate tumor and organ delineation via the use of four-dimensional computed tomography simulation, development of firm treatment planning guidelines, treatment verification using cone beam computed tomography, and a robust quality assurance program have all been instrumental in ensuring the safe and effective delivery of lung SABR. However, the process was laden with challenges, from delineating the optimum immobilization technique that balances patient comfort and motion, to introducing ways of making novice staff comfortable with a new method for treatment verification. CONCLUSIONS: There are outcome and toxicity data being collected on patients undergoing lung SABR at our cancer centre. This will serve as a self-assessment tool for our implementation process. Moreover, as future indications for SABR change, this initial implementation step will serve as a framework on which to continue building comprehensive guidelines.