•All but one endpoint maintained the same meta-conclusion over publication time.•New studies did not change the scientific conclusion of existing literature.•SFRT is equally as efficacious as ...MFRT.•The majority of included studies have low risk of bias.•Future resources should not be used to repeat these studies, and can be better allocated to test other hypotheses.
There has been a long-standing debate regarding the efficacy of single fraction radiotherapy (SFRT) compared to multiple fraction radiotherapy (MFRT); many systematic reviews and meta-analyses have been conducted to resolve the debate and suggested SFRT is equally as effective as MFRT. Given the adequate amalgamated sample size that exists, it is difficult to appreciate the need for further RCTs. The aim of this paper was to conduct a cumulative meta-analysis to determine whether further trials will be of value to the meta-conclusion. This paper also assessed publication quality.
A total of 29 studies were used in our meta-analysis. Comprehensive Meta-Analysis (Version 3) by Biostat was used to conduct a cumulative meta-analysis. The Cochrane Risk of Bias assessment tool was employed to assess study quality of the included RCTs. Funnel plots were generated using Review Manager (RevMan 5.3) by Cochrane IMS, to visually assess for publication bias.
All but one endpoint, overall response rates in assessable patients, maintained the same meta-conclusion over publication time; published studies did not change the amalgamated scientific conclusion of existing literature. Additional studies have simply confirmed pre-existing conclusions and refined the point estimate of the efficacy estimate. The majority of included studies have low risk of bias.
In conclusion, the meta-conclusion has remained consistent over time – SFRT is equally as efficacious as MFRT. Recent studies have had little impact on the overall conclusion, and given the vast amount of resources to execute a randomized trial, future resources should not be used to repeat these studies, and can be better allocated to test other hypotheses.
Small cell lung cancer (SCLC) is a lethal disease for which there have been only small advances in diagnosis and treatment in the past decade. Our goal was to revise the evidence-based guidelines on ...staging and best available treatment options.
A comprehensive literature search covering 2004 to 2011 was conducted in MEDLINE, Embase, and five Cochrane databases using SCLC terms. This was cross-checked with the authors' own literature searches and knowledge of the literature. Results were limited to research in humans and articles written in English.
The staging classification should include both the old Veterans Administration staging classification of limited stage (LS) and extensive stage (ES), as well as the new seventh edition American Joint Committee on Cancer/International Union Against Cancer staging by TNM. The use of PET scanning is likely to improve the accuracy of staging. Surgery is indicated for carefully selected stage I SCLC. LS disease should be treated with concurrent chemoradiotherapy in patients with good performance status. Thoracic radiotherapy should be administered early in the course of treatment, preferably beginning with cycle 1 or 2 of chemotherapy. Chemotherapy should consist of four cycles of a platinum agent and etoposide. ES disease should be treated primarily with chemotherapy consisting of a platinum agent plus etoposide or irinotecan. Prophylactic cranial irradiation prolongs survival in those individuals with both LS and ES disease who achieve a complete or partial response to initial therapy. To date, no molecularly targeted therapy agent has demonstrated proven efficacy against SCLC.
Evidence-based guidelines are provided for the staging and treatment of SCLC. LS-SCLC is treated with curative intent with 20% to 25% 5-year survival. ES-SCLC is initially responsive to standard treatment, but almost always relapses, with virtually no patients surviving for 5 years. Targeted therapies have no proven efficacy against SCLC.
RTOG 0617 compared standard-dose (SD; 60 Gy) versus high-dose (HD; 74 Gy) radiation with concurrent chemotherapy and determined the efficacy of cetuximab for stage III non-small-cell lung cancer ...(NSCLC).
The study used a 2 × 2 factorial design with radiation dose as 1 factor and cetuximab as the other, with a primary end point of overall survival (OS).
Median follow-up was 5.1 years. There were 3 grade 5 adverse events (AEs) in the SD arm and 9 in the HD arm. Treatment-related grade ≥3 dysphagia and esophagitis occurred in 3.2% and 5.0% of patients in the SD arm
12.1% and 17.4% in the HD arm, respectively (
= .0005 and < .0001). There was no difference in pulmonary toxicity, with grade ≥3 AEs in 20.6% and 19.3%. Median OS was 28.7
20.3 months (
= .0072) in the SD and HD arms, respectively, 5-year OS and progression-free survival (PFS) rates were 32.1% and 23% and 18.3% and 13% (
= .055), respectively. Factors associated with improved OS on multivariable analysis were standard radiation dose, tumor location, institution accrual volume, esophagitis/dysphagia, planning target volume and heart V5. The use of cetuximab conferred no survival benefit at the expense of increased toxicity. The prior signal of benefit in patients with higher H scores was no longer apparent. The progression rate within 1 month of treatment completion in the SD arm was 4.6%. For comparison purposes, the resultant 2-year OS and PFS rates allowing for that dropout rate were 59.6% and 30.7%, respectively, in the SD arms.
A 60-Gy radiation dose with concurrent chemotherapy should remain the standard of care, with the OS rate being among the highest reported in the literature for stage III NSCLC. Cetuximab had no effect on OS. The 2-year OS rates in the control arm are similar to the PACIFIC trial.
Sino-nasal cancer is rare and often diagnosed at advanced stages. Some patients cannot receive curative treatment and are treated with palliative irradiation. We aimed to identify prognostic factors ...for survival to facilitate treatment personalization for this group.
Twelve patients treated with palliative radiotherapy for locally advanced sino-nasal cancer were retrospectively analyzed for survival. Ten characteristics were evaluated including age, gender, Karnofsky performance score (KPS), pre-radiotherapy hemoglobin, tumor site, lymph node involvement, histology, equivalent dose in 2 Gy-fractions, completion of radiotherapy and concurrent chemotherapy.
On univariate analysis, KPS ≥70 (p<0.001) and completion of radiotherapy (p<0.001) were significantly associated with better survival. Chemotherapy showed a trend (p=0.097). In the multivariate analysis, KPS ≥70 was significant (p=0.025), and completion of radiotherapy showed a trend (p=0.080).
KPS is an independent predictor of survival for palliative irradiation of sino-nasal cancer. Patients require close monitoring and care for side effects, since completion of radiotherapy is important for survival.
Many patients with metastatic spinal cord compression (MSCC) live long enough to develop a recurrence in the irradiated spinal area. This is the first prospective study that has compared local ...control of different radiotherapy schedules for MSCC.
A total of 265 patients treated with radiotherapy alone were included in this prospective nonrandomized study. The primary goal was to compare local control from short-course (1 × 8 Gy/5 × 4 Gy, n = 131) and long-course radiotherapy (10 × 3 Gy/15 × 2.5 Gy/20 × 2 Gy, n = 134). Secondary end points were motor function and survival. The analysis of local control (no MSCC recurrence in the irradiated spinal area) included the 224 patients with improvement or no change of motor deficits during radiotherapy. Eleven additional factors were evaluated for outcomes.
One-year local control was 61% after short-course and 81% after long-course radiotherapy (p = 0.005). On multivariate analysis (MVA), improved local control was associated with long-course radiotherapy (p = 0.018). Motor function improved in 37% after short-course and 39% after long-course radiotherapy (p = 0.95). Improved motor function was associated with better performance status (p = 0.015), favorable tumor type (p = 0.034), and slower development of motor deficits (p < 0.001). One-year survival rates were 23% after short-course and 30% after long-course radiotherapy (p = 0.28). On MVA, improved survival was associated with better performance status (p < 0.001), no visceral metastases (p < 0.001), involvement of only one to three vertebrae (p = 0.040), ambulatory status (p = 0.038), and bisphosphonate administration after radiotherapy (p < 0.001).
Long-course radiotherapy was associated with better local control, similar functional outcome, and similar survival compared to short-course radiotherapy. Patients with a relatively favorable expected survival should receive long-course radiotherapy.
Purpose
Currently, in clinical practice of intensity‐modulated proton therapy (IMPT), the influence of the minimum monitor unit (MU) constraint is taken into account through postprocessing after the ...optimization is completed. This may degrade the plan quality and plan robustness. This study aims to mitigate the impact of the minimum MU constraint directly during the plan robust optimization.
Methods and materials
Cao et al. have demonstrated a two‐stage method to account for the minimum MU constraint using linear programming without the impact of uncertainties considered. In this study, we took the minimum MU constraint into consideration using quadratic optimization and simultaneously had the impact of uncertainties considered using robust optimization. We evaluated our method using seven cancer patients with different machine settings.
Result
The new method achieved better plan quality than the conventional method. The D95% of the clinical target volume (CTV) normalized to the prescription dose was (mean min–max): (99.4% 99.2%–99.6%) vs. (99.2% 98.6%–99.6%). Plan robustness derived from these two methods was comparable. For all seven patients, the CTV dose–volume histogram band gap (narrower band gap means more robust plans) at D95% normalized to the prescription dose was (mean min–max): (1.5% 0.5%–4.3%) vs. (1.2% 0.6%–3.8%).
Conclusion
Our new method of incorporating the minimum MU constraint directly into the plan robust optimization can produce machine‐deliverable plans with better tumor coverage while maintaining high‐plan robustness.
This study was conducted to determine if prophylactic cranial irradiation (PCI) improves survival in locally advanced non-small-cell lung cancer (LA-NSCLC).
Patients with stage III NSCLC without ...disease progression after treatment with surgery and/or radiation therapy (RT) with or without chemotherapy were eligible. Participants were stratified by stage (IIIA v IIIB), histology (nonsquamous v squamous), and therapy (surgery v none) and were randomly assigned to PCI or observation. PCI was delivered to 30 Gy in 15 fractions. The primary end point of the study was overall survival (OS). Secondary end points were disease-free survival (DFS), neurocognitive function (NCF), and quality of life. Kaplan-Meier and log-rank analyses were used for OS and DFS. The incidence of brain metastasis (BM) was evaluated with the logistic regression model.
Overall, 356 patients were accrued of the targeted 1,058. The study was closed early because of slow accrual; 340 of the 356 patients were eligible. The 1-year OS (P = .86; 75.6% v 76.9% for PCI v observation) and 1-year DFS (P = .11; 56.4% v 51.2% for PCI v observation) were not significantly different. The hazard ratio for observation versus PCI was 1.03 (95% CI, 0.77 to 1.36). The 1-year rates of BM were significantly different (P = .004; 7.7% v 18.0% for PCI v observation). Patients in the observation arm were 2.52 times more likely to develop BM than those in the PCI arm (unadjusted odds ratio, 2.52; 95% CI, 1.32 to 4.80).
In patients with stage III disease without progression of disease after therapy, PCI decreased the rate of BM but did not improve OS or DFS.
Standard treatment of glioblastoma multiforme (GBM) includes resection, longer-course radiotherapy and chemotherapy. Some patients cannot tolerate these regimens and may benefit from personalized ...treatments. This study aims to contribute to treatment personalization by identifying predictors of outcomes after longer-course radiotherapy.
In 91 patients, number/site/diameter of lesions, Ki-67, MGMT promoter methylation, Karnofsky performance score (KPS), symptoms, gender, age and resection were evaluated for local control and survival.
On univariate analyses, gross resection (p=0.029) was significantly associated with improved local control. It maintained significance in the multivariate analysis hazard ratio (HR)=1.64, p=0.025. MGMT-methylation (p=0.004), KPS ≥80 (p=0.022) and resection (p<0.001) were significantly associated with improved survival on univariate analyses, unifocal GBM (p=0.056) showed a trend. In the multivariate analyses, MGMT-methylation (HR=3.63, p=0.009), KPS (HR=2.01, p=0.018) and resection (HR=3.29, p<0.001) were significant.
Predictors of local control and survival were identified that may guide physicians when tailoring treatments to patients with GBM.
Patients requiring re-irradiation for recurrent glioblastoma multiforme (GBM) may benefit from individualized therapy. This study aimed to identify predictors of survival and contribute to treatment ...personalization.
In 28 patients with recurrent GBM, nine factors were analyzed for associations with survival: Main location and type of recurrence, Karnofsky performance score (KPS), age, gender, interval between primary radiotherapy and recurrence, gross total resection (GTR), equivalent dose in 2-Gy fractions (EQD2) of re-irradiation and cumulative EQD2 of primary and re-irradiation.
On univariate analyses, GTR (p=0.047), EQD2 ≥30 Gy (p=0.029) and cumulative EQD2 ≥90 Gy (p=0.023) were significantly associated with better survival; frontal location (p=0.119) and KPS 80-100% (p=0.067) showed trends. In multivariate analyses, frontal location (p=0.032) and cumulative EQD2 ≥90 Gy (p=0.038) were significant; KPS 80-100% (p=0.110) and EQD2 ≥30 Gy (p=0.083) showed trends.
Predictors of survival after re-irradiation for recurrent GBM were identified that can help when designing personalized treatments. Use of irradiation with EQD2 ≥30 Gy appeared superior to lower doses.
There are scant data regarding the effects of prophylactic cranial irradiation (PCI) on neurocognitive function (NCF) and quality of life (QOL). Radiation Therapy Oncology Group trial 0214 showed no ...overall survival (OS) benefit for PCI in stage III non-small-cell lung cancer (NSCLC) at 1 year. However, there was a significant decrease in brain metastases (BM). This analysis focuses on the impact of PCI on NCF and QOL.
Patients with stage III NSCLC who completed definitive therapy without progression were randomly assigned to PCI or observation. NCF was assessed with Mini-Mental Status Examination (MMSE), Activities of Daily Living Scale (ADLS), and Hopkins Verbal Learning Test (HVLT). QOL was assessed with the European Organisation for Research and Treatment of Cancer (EORTC) core tool (QOL Questionnaire-QLQC30) and brain module (QLQBN20).
There were no statistically significant differences at 1 year between the two arms in any component of the EORTC-QLQC30 or QLQBN20 (P > .05), although a trend for greater decline in patient-reported cognitive functioning with PCI was noted. There were no significant differences in MMSE (P = .60) or ADLS (P = .88). However, for HVLT, there was greater decline in immediate recall (P = .03) and delayed recall (P = .008) in the PCI arm at 1 year.
PCI in stage III NSCLC significantly decreases the risk of BM without improving 1-year OS. There were no significant differences in global cognitive function (MMSE) or QOL after PCI, but there was a significant decline in memory (HVLT) at 1 year. This study provides prospective data regarding the relative risks and benefits of PCI in this setting and the need to use sensitive cognitive assessments.
PDF
