Fundamentals of Radiation Oncology for Neurologic Imaging.

Although the physical and biologic principles of radiation therapy have remained relatively unchanged, a technologic renaissance has led to continuous and ever-changing growth in the field of radiation oncology. As a result, medical devices, techniques, and indications have changed considerably during the past 20-30 years. For example, advances in CT and MRI have revolutionized the treatment planning process for a variety of central nervous system diseases, including primary and metastatic tumors, vascular malformations, and inflammatory diseases. The resultant improved ability to delineate normal from abnormal tissue has enabled radiation oncologists to achieve more precise targeting and helped to mitigate treatment-related complications. Nevertheless, posttreatment complications still occur and can pose a diagnostic challenge for radiologists. These complications can be divided into acute, early-delayed, and late-delayed complications on the basis of the time that they manifest after radiation therapy and include leukoencephalopathy, vascular complications, and secondary neoplasms. The different irradiation technologies and applications of these technologies in the brain, current concepts used in treatment planning, and essential roles of the radiation oncologist in the setting of brain disease are reviewed. In addition, relevant imaging findings that can be used to delineate the extent of disease before treatment, and the expected posttreatment imaging changes are described. Common and uncommon complications related to radiation therapy and the associated imaging manifestations also are discussed. Familiarity with these entities may aid the radiologist in making the diagnosis and help guide appropriate management. ©RSNA, 2020.

Pre-treatment factors associated with detecting additional brain metastases at stereotactic radiosurgery.

The number of brain metastases identified on diagnostic magnetic resonance imaging (MRI) is a key factor in consideration of stereotactic radiosurgery (SRS). However, additional lesions are often detected on high-resolution SRS-planning MRI. We investigated pre-treatment clinical characteristics that are associated with finding additional metastases at SRS. Patients treated with SRS for brain metastases between the years of 2009-2014 comprised the study cohort. All patients underwent frame-fixed, 1 mm thick MRI on the day of SRS. Patient, tumor, and treatment characteristics were analyzed for an association with increase in number of metastases identified on SRS-planning MRI. 289 consecutive SRS cases were analyzed. 725 metastases were identified on pre-treatment MRI and 1062 metastases were identified on SRS-planning MRI. An increase in the number of metastases occurred in 34 % of the cases. On univariate analysis, more than four metastases and the diameter of the largest lesion were significantly associated with an increase in number of metastases on SRS-planning MRI. When stratified by the diameter of the largest lesion into <2, 2-3, or ≥3 cm, additional metastases were identified in 37, 29, and 18 %, respectively. While this increase in the number of metastases is largely due to the difference in imaging technique, the number and size of the metastases were also associated with finding additional lesions. These clinical factors may be considered when determining treatment options for brain metastases.

The Metastatic Spine Disease Multidisciplinary Working Group Algorithms.

The Metastatic Spine Disease Multidisciplinary Working Group consists of medical and radiation oncologists, surgeons, and interventional radiologists from multiple comprehensive cancer centers who have developed evidence- and expert opinion-based algorithms for managing metastatic spine disease. The purpose of these algorithms is to facilitate interdisciplinary referrals by providing physicians with straightforward recommendations regarding the use of available treatment options, including emerging modalities such as stereotactic body radiation therapy and percutaneous tumor ablation. This consensus document details the evidence supporting the Working Group algorithms and includes illustrative cases to demonstrate how the algorithms may be applied.

The development of stereotactic body radiotherapy in the past decade: a global perspective.

In the past 10 years, there has been an exponential increase in the incorporation of stereotactic body radiotherapy, also known as stereotactic ablative radiotherapy, into the armamentarium against various types of cancer in different settings worldwide. In this article in the 10th year anniversary issue of Future Oncology, representatives from the USA, Canada, Japan, Germany, The Netherlands, Australia and Singapore will provide individual perspectives of the development of stereotactic body radiotherapy in their respective countries.

A retrospective analysis of tumor volumetric responses to five-fraction stereotactic radiotherapy for paragangliomas of the head and neck (glomus tumors).

BACKGROUND: Skull base paragangliomas (SBP) are locally expansile tumors that can be treated with stereotactic radiotherapy with favorable results. This report describes the results of 31 patients with SBP treated with CyberKnife radiotherapy delivering a total dose of 25 Gray in five fractions. METHODS: All patients treated with five-fraction CyberKnife radiotherapy at a single institution were identified between 2007 and 2013. Tumor volumetric analyses were performed to assess responses to radiotherapy. RESULTS: Median follow-up was 24 months with a range of 4-78 months. Local control and overall survival were 100%. Of the 20 patients who presented with tinnitus, 12 reported improvement (60%), of whom 6 reported complete resolution. There was a 37.3% reduction in tumor volume among all patients (p = 0.16). On subset analysis of patients with ≥24 months of follow-up, tumor volume decreased 49% (p = 0.01). The rate of grade 1-2 toxicity was 19%, with no grade 3 or worse toxicity. CONCLUSION: A five-fraction CyberKnife-based stereotactic radiotherapy approach is safe and efficacious for the management for patients with SBP. Our findings suggest the potential use of this strategy as a definitive or salvage treatment option for SBP.

Long-Term Prospective Outcomes of Intensity Modulated Radiotherapy for Locally Advanced Lung Cancer: A Secondary Analysis of a Randomized Clinical Trial.

Importance: The optimal radiotherapy technique for unresectable locally advanced non-small cell lung cancer (NSCLC) is controversial, so evaluating long-term prospective outcomes of intensity-modulated radiotherapy (IMRT) is important. Objective: To compare long-term prospective outcomes of patients receiving IMRT and 3-dimensional conformal radiotherapy (3D-CRT) with concurrent carboplatin/paclitaxel for locally advanced NSCLC. Design, Setting, and Participants: A secondary analysis of a prospective phase 3 randomized clinical trial NRG Oncology-RTOG 0617 assessed 483 patients receiving chemoradiotherapy (3D-CRT vs IMRT) for locally advanced NSCLC based on stratification. Main Outcomes and Measures: Long-term outcomes were analyzed, including overall survival (OS), progression-free survival (PFS), time to local failure, development of second cancers, and severe grade 3 or higher adverse events (AEs) per Common Terminology Criteria for Adverse Events, version 3. The percentage of an organ volume (V) receiving a specified amount of radiation in units of Gy is reported as V(radiation dose). Results: Of 483 patients (median [IQR] age, 64 [57-70] years; 194 [40.2%] female), 228 (47.2%) received IMRT, and 255 (52.8%) received 3D-CRT (median [IQR] follow-up, 5.2 [4.8-6.0] years). IMRT was associated with a 2-fold reduction in grade 3 or higher pneumonitis AEs compared with 3D-CRT (8 [3.5%] vs 21 [8.2%]; P = .03). On univariate analysis, heart V20, V40, and V60 were associated with worse OS (hazard ratios, 1.06 [95% CI, 1.04-1.09]; 1.09 [95% CI, 1.05-1.13]; 1.16 [95% CI, 1.09-1.24], respectively; all P < .001). IMRT significantly reduced heart V40 compared to 3D-CRT (16.5% vs 20.5%; P < .001). Heart V40 (<20%) had better OS than V40 (≥20%) (median [IQR], 2.5 [2.1-3.1] years vs 1.7 [1.5-2.0] years; P < .001). On multivariable analysis, heart V40 (≥20%), was associated with worse OS (hazard ratio, 1.34 [95% CI, 1.06-1.70]; P = .01), whereas lung V5 and age had no association with OS. Patients receiving IMRT and 3D-CRT had similar rates of developing secondary cancers (15 [6.6%] vs 14 [5.5%]) with long-term follow-up. Conclusions and Relevance: These findings support the standard use of IMRT for locally advanced NSCLC. IMRT should aim to minimize lung V20 and heart V20 to V60, rather than constraining low-dose radiation bath. Lung V5 and age were not associated with survival and should not be considered a contraindication for chemoradiotherapy. Trial Registration: ClinicalTrials.gov Identifier: NCT00533949.

Stereotactic ablative radiotherapy (SABR) for non-small cell lung cancer.

Stereotactic ablative radiotherapy (SABR), otherwise known as stereotactic body radiation therapy (SBRT), is an external beam treatment modality that offers the ability to deliver with high precision large doses of radiation over a limited number of fractions. SABR is currently a standard of care in the treatment of early-stage primary non-small cell lung cancers (NSCLCs) that are medically inoperable and for metastases in many anatomical locations. To date, local control and toxicity parameters with SABR for early-stage NSCLCs are comparable to those found in reports of experiences with surgical resection. It is increasingly apparent that some patients with borderline resectable lung primaries are also looking to SABR as a noninvasive means of therapy. However, randomized comparisons have not been completed to assess survival in operable patients. This review summarizes the advanced technology and radiation concepts that have helped clinicians optimize the use of stereotactic ablative therapies for lung cancer, with an emphasis on the rationale for future continued use of this advanced treatment modality.

Modeling gamma knife radiosurgical toxicity for multiple brain metastases.

BACKGROUND AND PURPOSE: Radiation oncology protocols for single fraction radiosurgery recommend setting dosing criteria based on assumed risk of radionecrosis, which can be predicted by the 12 Gy normal brain volume (V12). In this study, we show that tumor surface area (SA) and a simple power-law model using only preplan variables can estimate and minimize radiosurgical toxicity. MATERIALS AND METHODS: A 245-patient cohort with 1217 brain metastases treated with single or distributed Gamma Knife sessions was reviewed retrospectively. Univariate and multivariable linear regression models and power-law models determined which modeling parameters best predicted V12. The V12 power-law model, represented by a product of normalized Rx dose Rxn, and tumor longest axial dimension LAD (V12 âˆ¼ Rxn1.5*LAD2), was independently validated using a secondary 63-patient cohort with 302 brain metastases. RESULTS: Surface area was the best univariate linear predictor of V12 (adjR2 = 0.770), followed by longest axial dimension (adjR2 = 0.755) and volume (adjR2 = 0.745). The power-law model accounted for 90% variance in V12 for 1217 metastatic lesions (adjR2 = 0.906) and 245 patients (adjR2 = 0.896). The average difference ΔV12 between predicted and measured V12s was (0.28 ± 0.55) cm3 per lesion and (1.0 ± 1.2) cm3 per patient. The power-law predictive capability was validated using a secondary 63-patient dataset (adjR2 = 0.867) with 302 brain metastases (adjR2 = 0.825). CONCLUSION: Surface area was the most accurate univariate predictor of V12 for metastatic lesions. We developed a preplan model for brain metastases that can help better estimate radionecrosis risk, determine prescription doses given a target V12, and provide safe dose escalation strategies without the use of any planning software.

Quality Metric to Assess Adequacy of Hydrogel Rectal Spacer Placement for Prostate Radiation Therapy and Association of Metric Score With Rectal Toxicity Outcomes.

Purpose: Although hydrogel spacer placement (HSP) minimizes rectal dose during prostate cancer radiation therapy, its potential benefit for modulating rectal toxicity could depend on the achieved prostate-rectal separation. We therefore developed a quality metric associated with rectal dose reduction and late rectal toxicity among patients treated with prostate stereotactic body radiation therapy (SBRT). Methods and Materials: A quality metric consisting of prostate-rectal interspace measurements from axial T2-weighted magnetic resonance imaging simulation images was applied to 42 men enrolled in a multi-institutional phase 2 study using HSP with prostate SBRT (45 Gy in 5 fractions). A score of 0, 1, or 2 was assigned to a prostate-rectal interspace measurement of <0.3 cm, 0.3 to 0.9 cm, or ≥1 cm, respectively. An overall spacer quality score (SQS) was computed from individual scores at rectal midline and ±1 cm laterally, located at the prostate base, midgland, and apex. Associations of SQS with rectal dosimetry and late toxicity were evaluated. Results: The majority of the analyzed cohort had an SQS of 1 (n = 17; 41%) or 2 (n = 18; 43%). SQS was associated with maximum rectal point dose (rectal Dmax; P = .002), maximum dose to 1 cc of rectum (D1cc; P = .004), and volume of rectum receiving ≥100% of prescription dose (V45; P = .046) and ≥40 Gy (V40; P = .005). SQS was also associated with a higher incidence of (P = .01) and highest-graded late rectal toxicity (P = .01). Among the 20 men who developed late grade ≥1 rectal toxicity, 57%, 71%, and 22% had an SQS of 0, 1, and 2, respectively. Men with an SQS of 0 or 1 compared with 2 had 4.67-fold (95% CI, 0.72-30.11) or 8.40-fold (95% CI, 1.83-38.57) greater odds, respectively, of developing late rectal toxicity. Conclusions: We developed a reliable and informative metric for assessing HSP, which appears to be associated with rectal dosimetry and late rectal toxicity after prostate SBRT.

Stereotactic Radiosurgery vs Conventional Radiotherapy for Localized Vertebral Metastases of the Spine: Phase 3 Results of NRG Oncology/RTOG 0631 Randomized Clinical Trial.

Importance: Spine metastasis can be treated with high-dose radiation therapy with advanced delivery technology for long-term tumor and pain control. Objective: To assess whether patient-reported pain relief was improved with stereotactic radiosurgery (SRS) as compared with conventional external beam radiotherapy (cEBRT) for patients with 1 to 3 sites of vertebral metastases. Design, Setting, and Participants: In this randomized clinical trial, patients with 1 to 3 vertebral metastases were randomized 2:1 to the SRS or cEBRT groups. This NRG 0631 phase 3 study was performed as multi-institutional enrollment within NRG Oncology. Eligibility criteria included the following: (1) solitary vertebral metastasis, (2) 2 contiguous vertebral levels involved, or (3) maximum of 3 separate sites. Each site may involve up to 2 contiguous vertebral bodies. A total of 353 patients enrolled in the trial, and 339 patients were analyzed. This analysis includes data extracted on March 9, 2020. Interventions: Patients randomized to the SRS group were treated with a single dose of 16 or 18 Gy (to convert to rad, multiply by 100) given to the involved vertebral level(s) only, not including any additional spine levels. Patients assigned to cEBRT were treated with 8 Gy given to the involved vertebra plus 1 additional vertebra above and below. Main Outcomes and Measures: The primary end point was patient-reported pain response defined as at least a 3-point improvement on the Numerical Rating Pain Scale (NRPS) without worsening in pain at the secondary site(s) or the use of pain medication. Secondary end points included treatment-related toxic effects, quality of life, and long-term effects on vertebral bone and spinal cord. Results: A total of 339 patients (mean [SD] age of SRS group vs cEBRT group, respectively, 61.9 [13.1] years vs 63.7 [11.9] years; 114 [54.5%] male in SRS group vs 70 [53.8%] male in cEBRT group) were analyzed. The baseline mean (SD) pain score at the index vertebra was 6.06 (2.61) in the SRS group and 5.88 (2.41) in the cEBRT group. The primary end point of pain response at 3 months favored cEBRT (41.3% for SRS vs 60.5% for cEBRT; difference, -19 percentage points; 95% CI, -32.9 to -5.5; 1-sided P = .99; 2-sided P = .01). Zubrod score (a measure of performance status ranging from 0 to 4, with 0 being fully functional and asymptomatic, and 4 being bedridden) was the significant factor influencing pain response. There were no differences in the proportion of acute or late adverse effects. Vertebral compression fracture at 24 months was 19.5% with SRS and 21.6% with cEBRT (P = .59). There were no spinal cord complications reported at 24 months. Conclusions and Relevance: In this randomized clinical trial, superiority of SRS for the primary end point of patient-reported pain response at 3 months was not found, and there were no spinal cord complications at 2 years after SRS. This finding may inform further investigation of using spine radiosurgery in the setting of oligometastases, where durability of cancer control is essential. Trial Registration: ClinicalTrials.gov Identifier: NCT00922974.

Consensus Quality Measures and Dose Constraints for Lung Cancer From the Veterans Affairs Radiation Oncology Quality Surveillance Program and ASTRO Expert Panel.

PURPOSE: For patients with lung cancer, it is critical to provide evidence-based radiation therapy to ensure high-quality care. The US Department of Veterans Affairs (VA) National Radiation Oncology Program partnered with the American Society for Radiation Oncology (ASTRO) as part of the VA Radiation Oncology Quality Surveillance to develop lung cancer quality metrics and assess quality of care as a pilot program in 2016. This article presents recently updated consensus quality measures and dose-volume histogram (DVH) constraints. METHODS AND MATERIALS: A series of measures and performance standards were reviewed and developed by a Blue-Ribbon Panel of lung cancer experts in conjunction with ASTRO in 2022. As part of this initiative, quality, surveillance, and aspirational metrics were developed for (1) initial consultation and workup; (2) simulation, treatment planning, and treatment delivery; and (3) follow-up. The DVH metrics for target and organ-at-risk treatment planning dose constraints were also reviewed and defined. RESULTS: Altogether, a total of 19 lung cancer quality metrics were developed. There were 121 DVH constraints developed for various fractionation regimens, including ultrahypofractionated (1, 3, 4, or 5 fractions), hypofractionated (10 and 15 fractionations), and conventional fractionation (30-35 fractions). CONCLUSIONS: The devised measures will be implemented for quality surveillance for veterans both inside and outside of the VA system and will provide a resource for lung cancer-specific quality metrics. The recommended DVH constraints serve as a unique, comprehensive resource for evidence- and expert consensus-based constraints across multiple fractionation schemas.

Stereotactic ablative radiotherapy for non-small cell lung cancer: rationale and outcomes.

Stereotactic ablative radiotherapy (SABR), also known in older reports as stereotactic body radiation therapy, represents an evolving and expanding radiation treatment option for many forms of local malignancy, from primary tumors to metastatic and recurrent disease. It involves the precise delivery of higher doses of external-beam radiation per treatment over a shortened treatment course compared with traditional regimens. SABR has become the standard of care for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC) and is becoming a more viable option for surgical candidates with early-stage primary NSCLCs who prefer noninvasive modalities of treatment. Although SABR is being used for the treatment of primary and metastatic disease in many sites of the body, such as the central nervous system, liver, pancreas, spine metastases, and isolated nodal disease in the mediastinum and abdomen, this article focuses on treatment of NSCLC in the thorax. Specifically, this review provides the rationale, evidence, and indications for treating early-stage lung cancers with SABR.

Dosimetric and deformation effects of image-guided interventions during stereotactic body radiation therapy of the prostate using an endorectal balloon.

PURPOSE: During stereotactic body radiation therapy (SBRT) for the treatment of prostate cancer, an inflatable endorectal balloon (ERB) may be used to reduce motion of the target and reduce the dose to the posterior rectal wall. This work assessed the dosimetric impact of manual interventions on ERB position in patients receiving prostate SBRT and investigated the impact of ERB interventions on prostate shape. METHODS: The data of seven consecutive patients receiving SBRT for the treatment of clinical stage T1cN0M0 prostate cancer enrolled in a multi-institutional, IRB-approved trial were analyzed. The SBRT dose was 50 Gy in five fractions to a planning target volume (PTV) that included the prostate (implanted with three fiducial markers) with a 3-5 mm margin. All plans were based on simulation images that included an ERB inflated with 60 cm(3) of air. Daily kilovoltage cone-beam computed tomography (CBCT) imaging was performed to localize the PTV, and an automated fusion with the planning images yielded displacements required for PTV relocalization. When the ERB volume and/or position were judged to yield inaccurate repositioning, manual adjustment (ERB reinflation and/or repositioning) was performed. Based on all 59 CBCT image sets acquired, a deformable registration algorithm was used to determine the dose received by, displacement of, and deformation of the prostate, bladder (BLA), and anterior rectal wall (ARW). This dose tracking methodology was applied to images taken before and after manual adjustment of the ERB (intervention), and the delivered dose was compared to that which would have been delivered in the absence of intervention. RESULTS: Interventions occurred in 24 out of 35 (69%) of the treated fractions. The direct effect of these interventions was an increase in the prostate radiation dose that included 95% of the PTV (D95) from 9.6 ± 1.0 to 10.0 ± 0.2 Gy (p = 0.06) and an increase in prostate coverage from 94.0% ± 8.5% to 97.8% ± 1.9% (p = 0.03). Additionally, ERB interventions reduced prostate deformation in the anterior-posterior (AP) direction, reduced errors in the sagittal rotation of the prostate, and increased the similarity in shape of the prostate to the radiotherapy plan (increased Dice coefficient from 0.76 ± 0.06 to 0.80 ± 0.04, p = 0.01). Postintervention decreases in prostate volume receiving less than the prescribed dose and decreases in the voxel-wise displacement of the prostate, bladder, and anterior rectal wall were observed, which resulted in improved dose-volume histogram (DVH) characteristics. CONCLUSIONS: Image-guided interventions in ERB volume and/or position during prostate SBRT were necessary to ensure the delivery of the dose distribution as planned. ERB interventions resulted in reductions in prostate deformations that would have prevented accurate localization of patient anatomy.

Intraduodenal sarcoma recurrence of retroperitoneal origin: an unusual cause for a duodenal obstruction.

Soft tissue sarcomas are uncommon tumors, and intraduodenal soft tissue sarcoma manifestation is even more rare. Only three cases of intraduodenal sarcomas have been reported in the literature thus far. Here, we report a case of an intraduodenal recurrence of a retroperitoneal sarcoma causing bowel obstruction. This unusual recurrence pattern likely relates to the patient's previous resection and radiation treatment, and highlights the benefits, limitations and follow-up strategies after multimodality treatment.

Socioeconomic and demographic determinants of radiation treatment and outcomes in glioblastoma patients.

Introduction: Poor outcomes in glioblastoma patients, despite advancing treatment paradigms, indicate a need to determine non-physiologic prognostic indicators of patient outcome. The impact of specific socioeconomic and demographic patient factors on outcomes is unclear. We sought to identify socioeconomic and demographic patient characteristics associated with patient survival and tumor progression, and to characterize treatment options and healthcare utilization. Methods: A cohort of 169 patients with pathologically confirmed glioblastomas treated at our institution was retrospectively reviewed. Multivariable cox proportional hazards analysis for overall survival (OS) and cumulative incidence of progression was performed. Differences in treatment regimen, patient characteristics, and neuro-oncology office use between different age and depressive disorder history patient subgroups were calculated two-sample t-tests, Fisher's exact tests, or linear regression analysis. Results: The median age of all patients at the time of initiation of radiation therapy was 60.5 years. The median OS of the cohort was 13.1 months. Multivariable analysis identified age (Hazard Ratio 1.02, 95% CI 1.00-1.04) and total resection (Hazard Ratio 0.52, 95% CI 0.33-0.82) as significant predictors of OS. Increased number of radiation fractions (Hazard Ratio 0.90, 95% CI 0.82-0.98), depressive disorder history (Hazard Ratio 0.59, 95% CI 0.37-0.95), and total resection (Hazard Ratio 0.52, 95% CI 0.31-0.88) were associated with decreased incidence of progression. Notably, patients with depressive disorder history were observed to have more neuro-oncology physician office visits over time (median 12 vs. 16 visits, p = 0.0121). Patients older than 60 years and those with Medicare (vs. private) insurance were less likely to receive as many radiation fractions (p = 0.0014) or receive temozolomide concurrently with radiation (Odds Ratio 0.46, p = 0.0139). Conclusion: Older glioblastoma patients were less likely to receive as diverse of a treatment regimen as their younger counterparts, which may be partially driven by insurance type. Patients with depressive disorder history exhibited reduced incidence of progression, which may be due to more frequent health care contact during neuro-oncology physician office visits.

Impact of CDKN2A/B, MTAP, and TERT Genetic Alterations on Survival in IDH Wild Type Glioblastomas.

PURPOSE: Poor outcomes in IDH wild-type (IDHwt) glioblastomas indicate the need to determine which genetic alterations can indicate poor survival and guidance of patient specific treatment options. We sought to identify the genetic alterations in these patients that predict for survival when adjusting particularly for treatments and other genetic alterations. METHODS: A cohort of 167 patients with pathologically confirmed IDHwt glioblastomas treated at our institution was retrospectively reviewed. Next generation sequencing was performed for each patient to determine tumor genetic alterations. Multivariable cox proportional hazards analysis for overall survival (OS) was performed to control for patient variables. RESULTS: CDKN2A, CDKN2B, and MTAP deletion predict for worse OS independently of other genetic alterations and patient characteristics (hazard ratio [HR] 2.192, p = 0.0017). Patients with CDKN2A copy loss (HR 2.963, p = 0.0037) or TERT mutated (HR 2.815, p = 0.0008) glioblastomas exhibited significant associations between radiation dose and OS, while CDKN2A and TERT wild type patients did not. CDKN2A deleted patients with NF1 mutations had worse OS (HR 1.990, p = 0.0540), while CDKN2A wild type patients had improved OS (HR 0.229, p = 0.0723). Patients with TERT mutated glioblastomas who were treated with radiation doses < 45 Gy (HR 3.019, p = 0.0010) but not those treated with ≥ 45 Gy exhibited worse OS compared to those without TERT mutations. CONCLUSION: In IDHwt glioblastomas, CDKN2A, CDKN2B, and MTAP predict for poor prognosis. TERT and CDKN2A mutations are associated with worse survival only when treated with lower radiation doses, thus potentially providing a genetic marker that can inform clinicians on proper dose-fractionation schemes.

Neutrophilia and post-radiation thrombocytopenia predict for poor prognosis in radiation-treated glioma patients.

Introduction: Poor outcomes in glioma patients indicate a need to determine prognostic indicators of survival to better guide patient specific treatment options. While preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) have been suggested as prognostic systemic inflammation markers, the impact of post-radiation changes in these cell types is unclear. We sought to identify which hematologic cell measurements before, during, or after radiation predicted for patient survival. Methods: A cohort of 182 patients with pathologically confirmed gliomas treated at our institution was retrospectively reviewed. Patient blood samples were collected within one month before, during, or within 3 months after radiation for quantification of hematologic cell counts, for which failure patterns were evaluated. Multivariable cox proportional hazards analysis for overall survival (OS) and progression-free survival (PFS) was performed to control for patient variables. Results: Multivariable analysis identified pre-radiation NLR > 4.0 (Hazard ratio = 1.847, p = 0.0039) and neutrophilia prior to (Hazard ratio = 1.706, p = 0.0185), during (Hazard ratio = 1.641, p = 0.0277), or after (Hazard ratio = 1.517, p = 0.0879) radiation as significant predictors of worse OS, with similar results for PFS. Post-radiation PLR > 200 (Hazard ratio = 0.587, p = 0.0062) and a percent increase in platelets after radiation (Hazard ratio = 0.387, p = 0.0077) were also associated with improved OS. Patients receiving more than 15 fractions of radiation exhibited greater post-radiation decreases in neutrophil and platelet counts than those receiving fewer. Patients receiving dexamethasone during radiation exhibited greater increases in neutrophil counts than those not receiving steroids. Lymphopenia, changes in lymphocyte counts, monocytosis, MLR, and changes in monocyte counts did not impact patient survival. Conclusion: Neutrophilia at any time interval surrounding radiotherapy, pre-radiation NLR, and post-radiation thrombocytopenia, but not lymphocytes or monocytes, are predictors of poor patient survival in glioma patients.

T Stage and Pretreatment Standardized Uptake Values Predict Tumor Recurrence With 5-Fraction SABR in Early-Stage Non-Small Cell Lung Cancer.

Purpose: Five-fraction stereotactic ablative radiotherapy (SABR) regimens are frequently used to treat centrally located early-stage non-small cell lung cancer or disease in the proximity of the chest wall as a means of optimizing tumor control and reducing treatment toxicity. However, increasing these SABR regimens to 5 fractions may reduce tumor control outcomes. We sought to identify the clinical parameters predictive of treatment failures with these 5-fraction courses. Methods: Ninety patients with T1-2 non-small cell lung cancer were treated with 50 or 60 Gy in 5 fractions. Failure over time was modeled using cumulative incidences of local, regional, or distant failure, with death as a competing risk. Cox proportional hazards analysis for incidences of failure was performed to control for patient variables. Results: Of 90 patients, 24 of 53 patients with T1 tumors and 19 of 37 patients with T2 tumors received 50 Gy SABR, and the other 47 patients received 60 Gy. Two-year overall survival and progression-free survival for the whole cohort were 75.8% and 59.3%, respectively. Total SABR dose (50 vs 60 Gy) did not influence survival nor failure rates at 2 and 5 years. Within 2 years of treatment, 7.8% of all patients developed local failure. For all patient and tumor characteristics evaluated, only T stage and pretreatment positron emission tomography standardized uptake values served as predictors of local, regional, and distant failure at 2 and 5 years posttreatment on univariate and multivariable analysis. Conclusions: Five-fraction SABR provides excellent in-field control. T2 and high fluorodeoxyglucose uptake tumors have increased failure rates, suggesting the potential need for adjuvant therapies, which are being assessed in randomized phase 3 trials.