Dosimetric comparison between Intensity Modulated Radiation Therapy (IMRT) vs dual arc Volumetric Arc Therapy (VMAT) for nasopharyngeal cancer (NPC): Systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Previous non-randomised studies comparing dosimetric outcomes between advanced techniques such as IMRT and VMAT reported conflicting findings. We thus sought to perform a systematic review and meta-analysis to consolidate the findings of these studies. MATERIALS AND METHODS: We searched PUBMED and EMBASE for eligible studies from their time of inception to 10 March 2022. A random effects model was used to estimate the pooled mean differences (MDs) and their 95% confidence intervals(CIs) for target volume coverage, organ-at-risk(OAR) doses, monitor units(MUs) and treatment delivery times. We also performed a subgroup analysis to evaluate if different treatment planning systems (TPS) (Eclipse, Monaco and Pinnacle) used affected the pooled mean differences. RESULTS: A total of 17 studies (383 patients) were eligible to be included. The pooled results showed that dual arc VMAT reduced D2% of PTV (MD=0.71Gy,95%CI=0.14-1.27,P=0.01), mean left cochlea dose (MD=2.6Gy,95%CI=0.03-5.16,P=0.05), mean right cochlea dose (MD=3.4Gy,95%CI=0.7-6.1,P=0.01), MUs (MD=554.9,95%CI=245.8-863.9,P=0.0004), treatment delivery times (MD=6.7mins,95%CI=4.5-8.9,P<0.0001) and integral dose (MD=0.97Gy,95%CI=0.28-1.67,P=0.006). None of the other indices were significantly better for the IMRT plans. The subgroup analysis showed that the integral dose was significantly lower only for Eclipse (MD=0.88Gy, 95%CI=0.14-1.63, P=0.02). The total MUs was significantly lower only for Eclipse (MD=1035.2, 95%CI=624.6-1445.9, P<0.0001) and Pinnacle (MD=293, 95%CI=15.6-570.5, P=0.04). Similarly, delivery time was also significantly lower only for Eclipse (MD=6.1mins, 95%CI=5.7-6.5, P<0.0001) and Pinnacle (MD=4.9mins, 95%CI=2.6-7.2, P<0.0001). The subgroup analysis however showed that target coverage was superior for the IMRT plans for both Pinnacle (MD=0.48Gy, 95%CI=0.31-0.66, P<0.0001) and Monaco (MD=0.12Gy, 95%CI=0.07-0.17, P<0.0001). CONCLUSION: Dual-arc VMAT plans improved OAR doses, MUs and treatment times as compared to IMRT plans. The different TPS used may modify dosimetric outcomes.

Quality of reporting of cranial irradiation techniques in randomized controlled trials of primary brain tumors: A systematic review.

BACKGROUND: To assess the quality of reporting of cranial irradiation (CR) techniques in randomized controlled trials (RCTs) of primary brain tumors. METHODS: We searched PubMed and EMBASE for RCTs of primary brain tumors, published from January 1999 to November 2019 which included CR as one of the intervention arms. We assessed the initial RCTs report on whether they reported the prespecified ten criteria for CR technique adequately. Multivariable logistic regression was performed to determine the factors that were predictive of adequate quality of reporting. RESULTS: We found 85 eligible trial reports. There was significant variability in the quality of reporting among the included studies. Total radiotherapy (RT) dose and fractionation schedule were reported adequately in more than 90% of the included trials. The organs at risk dose constraints, treatment verification procedures and presence or absence of deviations in RT treatment planning and delivery were reported adequately in less than 30% of included trials. Twenty-three trials (27%) reported seven criteria or more adequately. Multivariable analysis showed that trials conducted by cooperative groups, published RT quality assurance results and having a low risk of bias in the methodological quality have higher odds of having adequate quality in reporting of CR technique (judged as adequate reporting in seven criteria or more). CONCLUSIONS: The quality of reporting on CR techniques in the RCTs of primary brain tumors is variable and suboptimal. Guidelines should be introduced to improve clarity and ensure consistency in the quality of reporting.

Quality of reporting on thoracic radiotherapy technique in prospective lung cancer trials: A systematic review.

BACKGROUND: The aim of this study is to assess the quality of reporting of thoracic (T) RT technique for curative intent treatment in prospective lung cancer trials. METHODS: We searched MEDLINE for eligible trials published from 1996 to 2016. We assessed the included trials' reports on whether they reported the RT dose prescription method; RT dose-planning procedures; algorithm for tissue inhomogeneity dose corrections; organs at risk dose constraints; target volume definition, simulation and/or motion management procedures; treatment verification procedures; total RT dose; fractionation schedule; conduct of quality assurance as well as presence or absence of deviations in RT treatment planning and delivery adequately. We performed univariable and multivariable logistic regression to determine the factors that may influence the quality of reporting. RESULTS: We found 85 eligible trial reports. Target volume definition, total RT dose, and fractionation schedules were reported adequately in more than 90% of the included trials. Algorithm for tissue inhomogeneity dose corrections, simulation and verification procedures, presence or absence of deviations in RT treatment planning and delivery were reported adequately in less than 20% of the included trials. Twenty-three trials (27%) reported 7 criteria or more adequately. Both univariable and multivariable logistic regression showed that trials with RT focused research question were more likely to have adequate quality in reporting (judged as adequate reporting in 7 criteria or more) than trials with non-RT focused question (odds ratio 4.11, 95% confidence interval 1.10 to 15.43, P value = .04). CONCLUSION: There is significant variability in the quality of reporting on thoracic radiotherapy treatment in prospective lung cancer trials. Future research should focus on developing consensus guidelines to standardize the reporting of radiotherapy technique in clinical trials.

Chemoradiotherapy versus chemotherapy for locally advanced unresectable pancreatic cancer: A systematic review and meta-analysis.

PURPOSE: To determine the benefit of adding radiotherapy (RT) to chemotherapy for patients with locally advanced unresectable pancreatic cancer (LAUPC). METHODS: We searched MEDLINE for comparative studies comparing chemoradiotherapy with chemotherapy for patients with LAUPC. We performed the meta-analysis with random effects model. The primary outcome was overall survival (OS); secondary outcomes include progression-free survival (PFS) and adverse events (AE). RESULTS: We found five randomized (RCT) and three observational studies (OBS) including 830 patients. For RCTs, the addition of radiotherapy did not improve PFS (hazard ratio [HR] 0.90; 95% confidence interval [CI], 0.74-1.10; P = 0.30; I2   =  11%,) or OS (HR 0.87; 95% CI, 0.63-1.21; P = 0.41; I2 = 67%,) and was associated with increased grade 3 or 4 gastrointestinal AE. In contrast, OBS reported an improvement in PFS (HR 0.58; 95% CI, 0.37-0.92; P = 0.02; I2 = 32%) and OS (HR 0.48; 95% CI, 0.35-0.60; P < 0.0001; I2 = 6%). CONCLUSION: The addition of radiotherapy did not improve the OS and PFS in RCTs. The divergence in results seen in OBS may be due to imbalance in baseline characteristics. Further research incorporating biomarkers may help to better select patients who will benefit from RT.

Quality of radiotherapy reporting in randomized controlled trials of prostate cancer.

BACKGROUND: Good radiotherapy reporting in clinical trials of prostate radiotherapy is important because it will allow accurate reproducibility of radiotherapy treatment and minimize treatment variations that can affect patient outcomes. The aim of our study is to assess the quality of prostate radiotherapy (RT) treatment reporting in randomized controlled trials in prostate cancer. METHODS: We searched MEDLINE for randomized trials of prostate cancer, published from 1996 to 2016 and included prostate RT as one of the intervention arms. We assessed if the investigators reported the ten criteria adequately in the trial reports: RT dose prescription method; RT dose-planning procedures; organs at risk (OAR) dose constraints; target volume definition, simulation procedures; treatment verification procedures; total RT dose; fractionation schedule; conduct of quality assurance (QA) as well as presence or absence of deviations in RT treatment planning and delivery. We performed multivariate logistic regression to determine the factors that may influence the quality of reporting. RESULTS: We found 59 eligible trials. There was significant variability in the quality of reporting. Target volume definition, total RT dose and fractionation schedule were reported adequately in 97% of included trials. OAR constraints, simulation procedures and presence or absence of deviations in RT treatment planning and delivery were reported adequately in 30% of included trials. Twenty-four trials (40%) reported seven criteria or more adequately. Multivariable logistic analysis showed that trials that published their quality assurance results and cooperative group trials were more likely to have adequate quality in reporting in at least seven criteria. CONCLUSION: There is significant variability in the quality of reporting on prostate radiotherapy treatment in randomized trials of prostate cancer. We need to have consensus guidelines to standardize the reporting of radiotherapy treatment in randomized trials.

Outcomes of Asian patients with localized prostate cancer treated with combined intensity modulated radiation therapy (IMRT) and high dose rate (HDR) brachytherapy: A single institution experience.

AIM: External beam radiotherapy (EBRT) followed by high dose rate (HDR) brachytherapy boost has demonstrated minimal toxicities and improved disease control rate compared with EBRT alone in observational and randomized studies with predominantly Caucasian patients. This study aims to report the outcomes of patients treated with this approach in our predominantly Asian population. METHODS: Medical records for patients with localized prostate cancer who received combined EBRT delivered via intensity modulated radiotherapy (IMRT) technique followed by HDR brachytherapy boost were retrospectively reviewed. Outcomes evaluated included 5-year biochemical recurrence-free survival (per Phoenix definition), overall survival and treatment toxicities. RESULTS: From June 2009 to March 2015, 75 patients were treated with IMRT followed by HDR brachytherapy boost. Twenty patients (27%) had intermediate risk, 55 (74%) had high-risk disease. Median follow up was 64 months. All patients received IMRT to a median dose of 45 Gy to the pelvis followed by HDR brachytherapy boost. Sixty, 10 and 5 patients received boost of 21 Gy in two fractions, 19 Gy in two fractions and 15 Gy in a single fraction, respectively. All patients met the planning criteria adapted from RTOG 0815. The 5-year prostate-specific antigen (PSA) control was 85.2% (80.3% and 100% for high-risk and intermediate-risk group, respectively). Cancer-specific survival and overall survival are 97.3% and 92.0%, respectively. Eleven (15%) patients developed biochemical failure, six of which had distant metastasis. Three (4%) developed grade 3 genitourinary toxicity (urethral stricture and/or cystitis) and none developed grade 3 radiation proctitis. CONCLUSION: Our outcomes are comparable to internationally published data and demonstrate reproducibility of this approach in our population.

Efficacy of palliative radiation therapy for symptomatic rectal cancer.

99 patients with symptomatic locally advanced rectal cancer who were treated with palliative radiation alone were reviewed. Dose-fractionation ranged from 18 to 54Gy. Response rate ranged from 62.5 to 86.7%, with a median response duration ranging 4.2-5.4months. Median survival was 6.9months. Using a BED cut-off of 39Gy10, no dose-response relationship was found.

Prevalence and predictors of bias in the reporting of primary efficacy and toxicity endpoints in randomized clinical trials of radiation oncology.

INTRODUCTION: To determine the prevalence and predictors of bias in reporting of primary efficacy and toxicity endpoints in randomized trials (RCTs) of radiation oncology. METHODS: We searched MEDLINE for eligible RCTs published from January 1994 to October 2014. Bias in reporting of primary efficacy endpoint was defined as reporting that treatment was beneficial based on secondary endpoints despite a statistically non-significant difference in primary endpoint. Bias in reporting of toxicity endpoint was defined as not reporting toxicity findings in the abstract, discussion or results table. Logistic regression multivariate models were used to determine predictors of biased reporting. RESULTS: We found that 13% of 323 RCTs have bias in the reporting of primary efficacy endpoint with non-cooperative group trials as a significant predictor of bias (odds ratio (OR) 2.04, 95% confidence interval (CI) 1.03-4.00, P = 0.04). Thirty-five per cent of 279 RCTs were judged to have bias in the reporting of toxicity endpoint with trials not listed in Clinicaltrials.gov as a significant predictor of bias (OR 3.23, 95% CI 1.43-7.14, P = 0.004). CONCLUSION: The prevalence of bias in reporting of primary efficacy and toxicity endpoint for radiotherapy RCTs was 13% and 35% respectively. Non-cooperative group trials were more likely to have bias in the reporting of primary efficacy endpoint. Trials not listed in Clinicaltrials.gov were more likely to have bias in the reporting of toxicity endpoint.

Measuring radiotherapy setup errors at multiple neck levels in nasopharyngeal cancer (NPC): A case for differential PTV expansion.

BACKGROUND AND PURPOSE: We aim to quantify the magnitude of the systematic and random setup errors at three different anatomical levels of the neck in Nasopharyngeal Carcinoma (NPC) when clivus matching is used, and recommend appropriate PTV margins for each level. MATERIAL AND METHODS: Thirty-six patients undergoing image-guided radiotherapy (IGRT) each with 9 scheduled CBCTs were reviewed. The magnitude of setup errors were measured at the level of the clivus, C4 and C7 vertebrae, before and after CBCT correction. The 3D displacements, systematic and random errors were calculated for each level. The appropriate PTV expansion was determined using Van Herk's formula. RESULTS: Mean 3D displacement was 1.88, 2.66 and 3.35 mm at the clivus, C4 and C7 before correction. The differences were statistically significant (p<0.05). The PTV margin required without correction was 2.33, 4.33 and 6.52 mm respectively. These were reduced to 1.20, 3.72 and 6.08 mm after CBCT corrections. CONCLUSIONS: Variability is seen in setup errors at the clivus, C4 and C7 vertebral levels. A variable planning margin approach with reduced margin at the clivus is recommended. Use of daily CBCT allows the PTV expansion to be reduced to 1.2 mm.