Radiotherapy and temozolomide for newly diagnosed glioblastoma and anaplastic astrocytoma: validation of Radiation Therapy Oncology Group-Recursive Partitioning Analysis in the IMRT and temozolomide era

Since the development of the Radiation Therapy Oncology Group-Recursive Partitioning Analysis (RTOG-RPA) risk classes for high-grade glioma, radiation therapy in combination with temozolomide (TMZ) has become standard care. While this combination has improved survival, the prognosis remains poor in the majority of patients. Therefore, strong interest in high-grade gliomas from basic research to clinical trials persists. We sought to evaluate whether the current RTOG-RPA retains prognostic significance in the TMZ era or alternatively, if modifications better prognosticate the optimal selection of patients with similar baseline prognosis for future clinical protocols. The records of 159 patients with newly-diagnosed glioblastoma (GBM, WHO grade IV) or anaplastic astrocytoma (AA, WHO grade III) were reviewed. Patients were treated with intensity-modulated radiation therapy (IMRT) and concurrent followed by adjuvant TMZ (n = 154) or adjuvant TMZ only (n = 5). The primary endpoint was overall survival. Three separate analyses were performed: (1) application of RTOG-RPA to the study cohort and calculation of subsequent survival curves, (2) fit a new tree model with the same predictors in RTOG-RPA, and (3) fit a new tree model with an expanded predictor set. All analyses used a regression tree analysis with a survival outcome fit to formulate new risk classes. Overall median survival was 14.9 months. Using the RTOG-RPA, the six classes retained their relative prognostic significance and overall ordering, with the corresponding survival distributions significantly different from each other (P < 0.01, χ2 statistic = 70). New recursive partitioning limited to the predictors in RTOG-RPA defined four risk groups based on Karnofsky Performance Status (KPS), histology, age, length of neurologic symptoms, and mental status. Analysis across the expanded predictors defined six risk classes, including the same five variables plus tumor location, tobacco use, and hospitalization during radiation therapy. Patients with excellent functional status, AA, and frontal lobe tumors had the best prognosis. For patients with newly-diagnosed high-grade gliomas, RTOG-RPA classes retained prognostic significance in patients treated with TMZ and IMRT. In contrast to RTOG-RPA, in our modified RPA model, KPS rather than age represented the initial split. New recursive partitioning identified potential modifications to RTOG-RPA that should be further explored with a larger data set

Importance of Radiation Oncologist Experience Among Patients With Head-and-Neck Cancer Treated With Intensity-Modulated Radiation Therapy.

PurposeOver the past decade, intensity-modulated radiation therapy (IMRT) has replaced conventional radiation techniques in the management of head-and-neck cancers (HNCs). We conducted this population-based study to evaluate the influence of radiation oncologist experience on outcomes in patients with HNC treated with IMRT compared with patients with HNC treated with conventional radiation therapy.MethodsWe identified radiation providers from Medicare claims of 6,212 Medicare beneficiaries with HNC treated between 2000 and 2009. We analyzed the impact of provider volume on all-cause mortality, HNC mortality, and toxicity end points after treatment with either conventional radiation therapy or IMRT. All analyses were performed by using either multivariable Cox proportional hazards or Fine-Gray regression models controlling for potential confounding variables.ResultsAmong patients treated with conventional radiation, we found no significant relationship between provider volume and patient survival or any toxicity end point. Among patients receiving IMRT, those treated by higher-volume radiation oncologists had improved survival compared with those treated by low-volume providers. The risk of all-cause mortality decreased by 21% for every additional five patients treated per provider per year (hazard ratio [HR], 0.79; 95% CI, 0.67 to 0.94). Patients treated with IMRT by higher-volume providers had decreased HNC-specific mortality (subdistribution HR, 0.68; 95% CI, 0.50 to 0.91) and decreased risk of aspiration pneumonia (subdistribution HR, 0.72; 95% CI, 0.52 to 0.99).ConclusionPatients receiving IMRT for HNC had improved outcomes when treated by higher-volume providers. These findings will better inform patients and providers when making decisions about treatment, and emphasize the critical importance of high-quality radiation therapy for optimal treatment of HNC

The impact of radiotherapy costs on clinical outcomes in breast cancer.

Background and purposeIn cost-effective healthcare systems, the cost of services should parallel patient complexity or quality of care. The purpose of this study was to determine whether the cost of radiotherapy correlates with patient-related outcomes among a large cohort of breast cancer patients treated with adjuvant breast radiation.Materials and methods23,127 women with non-metastatic breast cancer undergoing radiotherapy after breast conservation surgery were identified from the Surveillance, Epidemiology, and End Results database from 2000 to 2009. Medicare reimbursements were used as a proxy for cost of radiotherapy, and Medicare claims were examined to identify local toxicities, and breast cancer-related endpoints. The impact of cost on these outcomes was studied with multivariable Fine-Gray models to account for competing risks.ResultsThe median cost (and interquartile range) of a course of breast radiation was $8100 ($6700-9700). Increased radiation costs were not associated with the occurrence of treatment-related toxicities (all p-values&gt;0.05), ipsilateral breast recurrence (p=0.55), or breast cancer-related mortality (p=0.55).ConclusionHigher costs for adjuvant radiation in breast cancer were not associated with a decreased risk of patient-related outcomes suggesting inefficiency in Medicare reimbursements. Future efforts should focus on prospective evaluation of alternative payment models for radiotherapy

Variation in the Cost of Radiation Therapy Among Medicare Patients With Cancer.

PurposeRadiation therapy represents a major source of health care expenditure for patients with cancer. Understanding the sources of variability in the cost of radiation therapy is critical to evaluating the efficiency of the current reimbursement system and could shape future policy reform. This study defines the magnitude and sources of variation in the cost of radiation therapy for a large cohort of Medicare beneficiaries.Patients and methodsWe identified 55,288 patients within the SEER database diagnosed with breast, lung, or prostate cancer between 2004 and 2009. The cost of radiation therapy was estimated from Medicare reimbursements. Multivariable linear regression models were used to assess the influence of patient, tumor, and radiation therapy provider characteristics on variation in cost of radiation therapy.ResultsFor breast, lung, and prostate cancers, the median cost (interquartile range) of a course of radiation therapy was $8,600 ($7,300 to $10,300),$9,000 ($7,500 to$11,100), and $18,000 ($11,300 to $25,500), respectively. For all three cancer subtypes, patient- or tumor-related factors accounted for &lt; 3% of the variation in cost. Factors unrelated to the patient, including practice type, geography, and individual radiation therapy provider, accounted for a substantial proportion of the variation in cost, ranging from 44% with breast, 43% with lung, and 61% with prostate cancer.ConclusionIn this study, factors unrelated to the individual patient accounted for the majority of variation in the cost of radiation therapy, suggesting potential inefficiency in health care expenditure. Future research should determine whether this variability translates into improved patient outcomes for further evaluation of current reimbursement practices

Importance of Radiation Oncologist Experience Among Patients With Head-and-Neck Cancer Treated With Intensity-Modulated Radiation Therapy

Purpose Over the past decade, intensity-modulated radiation therapy (IMRT) has replaced conventional radiation techniques in the management of head-and-neck cancers (HNCs). We conducted this population-based study to evaluate the influence of radiation oncologist experience on outcomes in patients with HNC treated with IMRT compared with patients with HNC treated with conventional radiation therapy. Methods We identified radiation providers from Medicare claims of 6,212 Medicare beneficiaries with HNC treated between 2000 and 2009. We analyzed the impact of provider volume on all-cause mortality, HNC mortality, and toxicity end points after treatment with either conventional radiation therapy or IMRT. All analyses were performed by using either multivariable Cox proportional hazards or Fine-Gray regression models controlling for potential confounding variables. Results Among patients treated with conventional radiation, we found no significant relationship between provider volume and patient survival or any toxicity end point. Among patients receiving IMRT, those treated by higher-volume radiation oncologists had improved survival compared with those treated by low-volume providers. The risk of all-cause mortality decreased by 21% for every additional five patients treated per provider per year (hazard ratio [HR], 0.79; 95% CI, 0.67 to 0.94). Patients treated with IMRT by higher-volume providers had decreased HNC-specific mortality (subdistribution HR, 0.68; 95% CI, 0.50 to 0.91) and decreased risk of aspiration pneumonia (subdistribution HR, 0.72; 95% CI, 0.52 to 0.99). Conclusion Patients receiving IMRT for HNC had improved outcomes when treated by higher-volume providers. These findings will better inform patients and providers when making decisions about treatment, and emphasize the critical importance of high-quality radiation therapy for optimal treatment of HNC. (C) 2016 by American Society of Clinical OncologyNational Institutes of Health [KL2 TR001444, TL1 TR001443]SCI(E)[email protected]+3

Variation in the Cost of Radiation Therapy Among Medicare Patients With Cancer.

PurposeRadiation therapy represents a major source of health care expenditure for patients with cancer. Understanding the sources of variability in the cost of radiation therapy is critical to evaluating the efficiency of the current reimbursement system and could shape future policy reform. This study defines the magnitude and sources of variation in the cost of radiation therapy for a large cohort of Medicare beneficiaries.Patients and methodsWe identified 55,288 patients within the SEER database diagnosed with breast, lung, or prostate cancer between 2004 and 2009. The cost of radiation therapy was estimated from Medicare reimbursements. Multivariable linear regression models were used to assess the influence of patient, tumor, and radiation therapy provider characteristics on variation in cost of radiation therapy.ResultsFor breast, lung, and prostate cancers, the median cost (interquartile range) of a course of radiation therapy was $8,600 ($7,300 to $10,300),$9,000 ($7,500 to$11,100), and $18,000 ($11,300 to $25,500), respectively. For all three cancer subtypes, patient- or tumor-related factors accounted for &lt; 3% of the variation in cost. Factors unrelated to the patient, including practice type, geography, and individual radiation therapy provider, accounted for a substantial proportion of the variation in cost, ranging from 44% with breast, 43% with lung, and 61% with prostate cancer.ConclusionIn this study, factors unrelated to the individual patient accounted for the majority of variation in the cost of radiation therapy, suggesting potential inefficiency in health care expenditure. Future research should determine whether this variability translates into improved patient outcomes for further evaluation of current reimbursement practices

The Impact of Radiation Oncologists on the Early Adoption of Hypofractionated Radiation Therapy for Early-Stage Breast Cancer.

PurposeDespite multiple randomized trials showing the efficacy of hypofractionated radiation therapy in early-stage breast cancer, the United States has been slow to adopt this treatment. The goal of this study was to evaluate the impact of individual radiation oncologists on the early adoption of hypofractionated radiation therapy for early-stage breast cancer.MethodsWe identified 22,233 Medicare beneficiaries with localized breast cancer that was diagnosed from 2004 to 2011 who underwent breast-conserving surgery with adjuvant radiation. Multilevel, multivariable logistic models clustered by radiation oncologist and geographic practice area were used to determine the impact of the provider and geographic region on the likelihood of receiving hypofractionated compared with standard fractionated radiation therapy while controlling for a patient's clinical and demographic covariates. Odds ratios (OR) describe the impact of demographic or clinical covariates, and the median OR (MOR) describes the relative impact of the individual radiation oncologist and geographic region on the likelihood of undergoing hypofractionated radiation therapy.ResultsAmong the entire cohort, 2333 women (10.4%) were treated with hypofractionated radiation therapy, with unadjusted rates ranging from 0.0% in the bottom quintile of radiation oncologists to 30.4% in the top quintile. Multivariable analysis found that the individual radiation oncologist (MOR 3.08) had a greater impact on the use of hypofractionation than did geographic region (MOR 2.10) or clinical and demographic variables. The impact of the provider increased from the year 2004 to 2005 (MOR 2.82) to the year 2010 to 2011 (MOR 3.16) despite the publication of long-term randomized trial results in early 2010. Male physician and radiation oncologists treating the highest volume of breast cancer patients were less likely to perform hypofractionation (P&lt;.05).ConclusionsThe individual radiation oncologist strongly influenced the likelihood of a patient's receiving hypofractionated radiation therapy, and this trend increased despite the publication of long-term data showing equivalence to standard fractionation. Future research should focus on physician-related factors that influence this decision

Correlation of liver and pancreas tumor motion with normal anatomical structures determined with deformable image registration

Purpose. The inherent difficulty of identifying liver and pancreas tumors without intravenous contrast creates the need for implanted metal fiducials to visualize tumor position and motion in stereotactic body radiation therapy (SBRT). Unfortunately, the invasive procedure of implanting fiducials carries a risk of toxicity, introduces a treatment delay, and creates streak artifacts on treatment planning images, which can hinder tumor identification. A fiducial-less motion management strategy would improve the safety, tolerability, and availability of abdominal SBRT. We hypothesized that upper abdominal tumor motion would correlate with the motion of nearby organs and could thereby serve as a fiducial-less proxy for tumor motion. Methods. We retrospectively identified fifteen patients with pancreatic cancer or liver cancer treated with SBRT. The liver, superior mesenteric artery, and celiac artery were delineated on 4DCT images and used to predict tumor position. The correlation with tumor motion was quantified with Pearson correlation coefficients (r), and accuracy of the tumor position prediction was expressed as the mean absolute error. Results. The majority of motion with respiration occurred in the superior-inferior (SI) direction with an average of 6.4 mm (range 2.4-11.3 mm) for pancreatic and 13.0 mm (range 6.4-21.2 mm) for liver tumors. In the SI direction we found a tight correlation between liver and tumor motion in pancreas cancer patients (r = 0.92 0.10), and liver tumor patients (r = 0.97 0.02). Using the liver as surrogate, predicted tumor location was on average 0.5 mm from the actual position and not greater than 3.0 mm. Conclusions. This study demonstrates a potential correlation of normal organ and tumor motion which could serve as a fiducial-less surrogate for SBRT in the upper abdomen as on-site 4D volumetric imaging becomes available during treatment. Moving this motion management strategy into the clinic requires additional research to optimize 4D image quality and understand inter-fraction reproducibility

The Impact of Radiation Oncologists on the Early Adoption of Hypofractionated Radiation Therapy for Early-Stage Breast Cancer.

PurposeDespite multiple randomized trials showing the efficacy of hypofractionated radiation therapy in early-stage breast cancer, the United States has been slow to adopt this treatment. The goal of this study was to evaluate the impact of individual radiation oncologists on the early adoption of hypofractionated radiation therapy for early-stage breast cancer.MethodsWe identified 22,233 Medicare beneficiaries with localized breast cancer that was diagnosed from 2004 to 2011 who underwent breast-conserving surgery with adjuvant radiation. Multilevel, multivariable logistic models clustered by radiation oncologist and geographic practice area were used to determine the impact of the provider and geographic region on the likelihood of receiving hypofractionated compared with standard fractionated radiation therapy while controlling for a patient's clinical and demographic covariates. Odds ratios (OR) describe the impact of demographic or clinical covariates, and the median OR (MOR) describes the relative impact of the individual radiation oncologist and geographic region on the likelihood of undergoing hypofractionated radiation therapy.ResultsAmong the entire cohort, 2333 women (10.4%) were treated with hypofractionated radiation therapy, with unadjusted rates ranging from 0.0% in the bottom quintile of radiation oncologists to 30.4% in the top quintile. Multivariable analysis found that the individual radiation oncologist (MOR 3.08) had a greater impact on the use of hypofractionation than did geographic region (MOR 2.10) or clinical and demographic variables. The impact of the provider increased from the year 2004 to 2005 (MOR 2.82) to the year 2010 to 2011 (MOR 3.16) despite the publication of long-term randomized trial results in early 2010. Male physician and radiation oncologists treating the highest volume of breast cancer patients were less likely to perform hypofractionation (P&lt;.05).ConclusionsThe individual radiation oncologist strongly influenced the likelihood of a patient's receiving hypofractionated radiation therapy, and this trend increased despite the publication of long-term data showing equivalence to standard fractionation. Future research should focus on physician-related factors that influence this decision