Factors Associated with Long-Term Prostate Cancer Survival after Palliative Radiotherapy to a Bone Metastasis and Contemporary Palliative Systemic Therapy: A Retrospective, Population-Based Study.

BACKGROUND: Radiation therapy (RT) is an established palliative treatment for bone metastases; however, little is known about post-radiation survival and factors which impact it. The aim of this study was to assess a population-based sample of metastatic prostate cancer patients receiving palliative radiation therapy to bone metastases and contemporary palliative systemic therapy and identify factors that impact long-term survival. MATERIALS/METHODS: This retrospective, population-based, cohort study assessed all prostate cancer patients receiving palliative RT for bone metastases at a Canadian provincial Cancer program during a contemporary time period. Baseline patient, disease, and treatment characteristics were extracted from the provincial medical physics databases and the electronic medical record. Post-RT Survival intervals were defined as the time interval from the first fraction of palliative RT to death from any cause or date of the last known follow-up. The median survival of the cohort was used to dichotomize the cohort into short- and long-term survivors following RT. Univariable and multivariable hazard regression analyses were performed to identify variables associated with post-RT survival. RESULTS: From 1 January 2018 until 31 December 2019, 545 palliative RT courses for bone metastases were delivered to n = 274 metastatic prostate cancer patients with a median age of 76 yrs (Interquartile range (IQR) 39-83) and a median follow-up of 10.6 months (range 0.2 to 47.9). The median survival of the cohort was 10.6 months (IQR 3.5-25 months). The ECOG performance status of the whole cohort was ≤2 in n = 200 (73%) and 3-4 in n = 67 (24.5%). The most commonly treated sites of bone metastasis were the pelvis and lower extremities n = 130 (47.4%), skull and spine n = 114 (41.6%), and chest and upper extremities n = 30 (10.9%). Most patients had CHAARTED high volume disease n = 239 (87.2%). On multivariable hazard regression analysis, an ECOG performance status of 3-4 (p = 0.02), CHAARTED high volume disease burden (p = 0.023), and non-receipt of systemic therapy (p = 0.006) were significantly associated with worse post-RT survival. CONCLUSION: Amongst metastatic prostate cancer patients treated with palliative radiotherapy to bone metastases and modern palliative systemic therapies, ECOG performance status, CHAARTED metastatic disease burden, and type of first-line palliative systemic therapy were significantly associated with post-RT survival durations.

Do Sustainable Palliative Single Fraction Radiotherapy Practices Proliferate or Perish 2 Years after a Knowledge Translation Campaign?

In early 2017, the Canadian Partnership Against Cancer and CancerCare Manitoba undertook a comprehensive knowledge translation (KT) campaign to improve the utilization of single fraction radiotherapy (SFRT) over multiple fraction radiotherapy (MFRT) for palliative management of bone metastases. The campaign significantly increased short-term SFRT utilization. We assess the time-dependent effects of KT-derived SFRT utilization 12-24 months removed from the KT campaign in a Provincial Cancer Program. This study identified patients receiving palliative radiotherapy for bone metastases in Manitoba in the 2018 calendar year using the provincial radiotherapy database. The proportion of patients treated with SFRT in 2018 was compared to 2017. Logistic regression analyses identified risk factors associated with MFRT receipt. In 2018, 1008 patients received palliative radiotherapy for bone metastasis, of which 63.3% received SFRT, a small overall increase in SFRT use over 2017 (59.1%). However, 41.1% of ROs demonstrated year-over-year decreases in SFRT utilization, indicative of a time-dependent loss of SFRT prescription habits derived from KT. Although SFRT use increased slightly overall in 2018, evidence of compliance fatigue was observed, suggestive of a time-perishing property of RO prescription behaviours derived from KT methodologies. Verification of the study's findings in larger cohorts would be beneficial. These findings highlight the need for additional longitudinal KT reinforcement practices in the years following KT campaigns.

A retrospective study on clinical factors influencing intra-fraction motion using volumetric imaging for spine stereotactic body radiotherapy.

Objectives: Stereotactic body radiation therapy (SBRT) for the spine is challenging due to high-dose gradients sparing the cord in the treatment plans. We present our findings of initial setup error and intrafraction motion from Cone-beam computed tomography (CBCT) imaging. Materials and methods: A total of 47 patients treated with spine SBRT with a total of 154 fractions following a fractionation schedule of 16 Gy in 1, 24 Gy in 2, and 30 Gy in 5 fractions were part of this study. Pre-treatment CBCT was used for localization of the target and couch shifts were applied based on target volume matching to the planning CT image set. Post-treatment CBCT was acquired for all fractions. Intrafraction motion (IFM) was calculated by matching post-treatment CBCT to planning CT for the target volume. Results: The average Intrafraction motion was 1.6 ± 0.9 mm for the study cohort. The average and standard deviation of intrafraction motion were 0.4 ± 1.1 (AP), 0.3 ± 0.9 (SI) and 0.2 ± 1.2 (RL) respectively. The average Initial setup error tabulated from the offline review showed a mean value of 7.8 ± 5.3 mm. The average and standard deviation of the initial setup error were 2.5 ± 5.5 (AP), 2.4 ± 5.3(SI), and 0.8 ± 4.5(RL) respectively. The correlation of intrafraction motion with body mass index (BMI) and the number of consecutive vertebrae levels did not show any statistical significance, however, there was a significant association with gender as women showed more IFM. Conclusions: Our study on intrafraction motion from CBCT images reinforced the importance of immobilization and imaging for positioning spine SBRT patients. Advances in knowledge: The need for CBCT and imagining for positional errors is emphasized while treating with SBRT spine and the need for proper immobilization techniques.

Adaptive radiation therapy strategies in the treatment of prostate cancer patients using hypofractionated VMAT.

PURPOSE: To perform a comprehensive evaluation of eight adaptive radiation therapy strategies in the treatment of prostate cancer patients who underwent hypofractionated volumetric modulated arc therapy (VMAT) treatment. MATERIAL AND METHODS: The retrospective study included 20 prostate cancer patients treated with 40 Gy total dose over five fractions (8 Gy/fraction) using VMAT. Daily cone beam computed tomography images were acquired before the delivery of every fraction and then, with the application of deformable image registration used for the estimation of daily dose, contouring and plan re-optimization. Dosimetric benefits of the various ART strategies were quantified by the comparison of dose and dose-volume metrics derived from treatment planning objectives for original treatment plan and adapted plans with the consideration of target volumes (PTV and CTV) as well as critical structures (bladder, rectum, left, and right femoral heads). RESULTS: Percentage difference (ΔD) between planning objectives and delivered dose in the D99%  > 4000cGy (CTV) metric was -3.9% for the non-ART plan and 2.1% to 4.1% for ART plans. For D99%  > 3800cGy and Dmax  < 4280cGy (PTV), ΔD was -11.2% and -6.5% for the non-ART plan as well as -3.9% to -1.6% and -0.2% to 1.8% for ART plans, respectively. For D15%  < 3200 cGy and D20%  < 2800 cGy (bladder), ΔD was -62.4% and -68.8% for the non-ART plan as well as -60.0% to -57.4% and -67.0% to -64.0% for ART plans. For D15%  < 3200 cGy and D20%  < 2800 cGy (rectum), ΔD was -11.4% and -8.15% for non-ART plan as well as -14.9% to -9.0% and -11.8% to -5.1% for ART plans. CONCLUSIONS: Daily on-line adaptation approaches were the most advantageous, although strategies adapting every other fraction were also impactful while reducing relative workload as well. Offline treatment adaptations were shown to be less beneficial due to increased dose delivered to bladder and rectum compared toother ART strategies.

Do Coordinated Knowledge Translation Campaigns Persuade Radiation Oncologists to Use Single-Fraction Radiation Therapy Compared With Multiple-Fraction Radiation Therapy for Bone Metastases?

PURPOSE: Although level 1 evidence supports the use of single-fraction radiation therapy (SFRT) compared with multiple-fraction radiation therapy (MFRT) for the palliative management of bone metastases, SFRT is underused. In early 2017, the Canadian Partnership Against Cancer and CancerCare Manitoba undertook a comprehensive knowledge translation campaign in Manitoba, Canada featuring educational outreach visits, local consensus meetings, and audit and feedback interventions to encourage greater use of SFRT. This study assessed the impact of this campaign on SFRT use and identified variables associated with MFRT usage. METHODS AND MATERIALS: This retrospective, population-based cohort study identified all patients treated with palliative radiation therapy for bone metastases in Manitoba, Canada, from January 1, 2017, to December 31, 2017, using the provincial radiation therapy database. Baseline characteristics were extracted and tabulated by fractionation schedule. The proportion of patients treated with SFRT in 2017 (postintervention) was compared with the 2016 (preintervention) levels. Univariable and multivariable logistic regression analyses were performed to identify risk factors associated with MFRT use. RESULTS: In 2017, 927 patients received palliative radiation therapy for bone metastasis, of which 548 (59.1%) received SFRT, a 21.1% absolute increase in SFRT use compared with 2016 levels (38.0%). With use of multivariable analysis, variables associated with receipt of MFRT included: complicated bone metastasis, soft tissue extension, hematological primary malignancy, and treatment at a subsidiary center. CONCLUSION: The comprehensive knowledge translation campaign carried out in Manitoba resulted in a significant increase in SFRT use for bone metastases. Continued audit/feedback strategies are recommended to further reinforce knowledge translation efforts supporting SFRT use in the future.

Epidemiology, clinical treatment patterns, and survival of hepatocellular carcinoma in Manitoba.

Background: Hepatocellular carcinoma (HCC) has a very poor survival rate, especially for those who do not receive a potentially curative therapy. Methods: Treatment details were collected for 320 HCC patients diagnosed in Manitoba between January 2011 and December 2015. Patients had a mean age of 67.3 years, and 71.6% were men. Of these patients, 67 (20.9%) received curative treatment, 36 (11.3%) received non-curative treatment, and 217 (67.8%) received supportive care only; 71.3% of patients had liver cirrhosis. Alcoholic cirrhosis was the most common etiology of chronic liver disease (22.2%). Results: Those who received curative treatment had a significantly lower incidence of portal vein thrombosis and multinodular disease than those in other groups. Patients who received supportive care only had a higher incidence of ascites. We found no difference in the distribution of cirrhosis or portal hypertension among the treatment groups. The 2- and 5-year overall survival rates for the whole cohort were 27% and 14%, respectively. No significant change was found in 2-year survival for patients diagnosed in each year from 2011 to 2015 (p = 0.250). Also, we found no significant change in proportion of treatment given to patients over the same period (p = 0.432). Conclusion: The poor survival rate of HCC patients in Manitoba could potentially be improved by maximizing the use of local therapy and by implementing multidisciplinary-based case discussion. Efforts should also be directed toward early management of infective, alcoholic, and non-alcoholic steatohepatitis, which will, we hope, lead to a reduction in the incidence of HCC.

Hurdles in radiation planning for glioblastoma: Can delayed-contrast enhanced computed tomography be a potential solution?

OBJECTIVE: Conformal radiation is the standard of care in treatment of glioblastoma. Although co-registration of magnetic resonance imaging (MRI) with early contrast enhanced computed tomography (CECT) is recommended for target delineation by consensus guidelines, ground realities in developing countries often result in availability of less-than-ideal MR sequences for treatment planning. Purpose of this study is to analyze the impact of incorporation of delayed-CECT sequences for radiation planning in glioblastomas, as an adjunct or alternative to MRI. METHODS: Case records of all patients of glioblastoma treated at our center between 2011 and 2014 were retrospectively evaluated. Gross treatment volumes were delineated on T1 contrast MRI (m-GTV), early CECT (e-GTV) and delayed CECT (d-GTV); volumetric comparisons were made using repeated measures analysis of variance and pair-wise analysis. RESULTS: Although 96% of registered patients underwent postoperative MRI, only 38% of them had desirable sequences suitable for co-registration. Median duration between acquisition of postoperative MRI and surgery was 45 days (range, 33-60), whereas that between MRI and treatment-planning CT was 5 days (range, 1-10). Statistically significant differences (P < 0.0001) were obtained between mean volumes of e-GTV (41.20cc), d-GTV (58.09cc) and m-GTV (60.52cc). Although the mean GTV increased by 46% between early CECT and MRI, the difference was only 4% between delayed CECT and MRI. CONCLUSION: Delayed CECT is superior to early CECT for co-registration with MRI for target delineation, especially when available MR sequences are less-than-ideal for treatment planning, and can be considered as the most appropriate adjunct as well as an alternative to MRI, compared to early CECT.