Neutrophil to lymphocyte ratio (NTLR) predicts local control and overall survival after stereotactic body radiotherapy (SBRT) in metastatic sarcoma.

The neutrophil to lymphocyte ratio (NTLR) and absolute lymphocyte count (ALC) recovery are prognostic across many cancers. We investigated whether NLTR predicts SBRT success or survival in a metastatic sarcoma cohort treated with SBRT from 2014 and 2020 (N = 42). Wilcox Signed Rank Test and Friedman Test compare NTLR changes with local failure vs. local control (N = 138 lesions). Cox analyses identified factors associated with overall survival. If local control was successful, NLTR change was not significant (p = 0.30). However, NLTR significantly changed in patients with local failure (p = 0.027). The multivariable Cox model demonstrated higher NLTR before SBRT was associated with worse overall survival (p = 0.002). The optimal NTLR cut point was 5 (Youden index: 0.418). One-year overall survival in SBRT metastatic sarcoma cohort was 47.6% (CI 34.3%-66.1%). Patients with an NTLR above 5 had a one-year overall survival of 37.7% (21.4%-66.3%); patients with an NTLR below 5 had a significantly improved overall survival of 63% (43.3%-91.6%, p = 0.014). Since NTLR at the time of SBRT was significantly associated with local control success and overall survival in metastatic sarcoma treated with SBRT, future efforts to reduce tumor inhibitory microenvironment factors and improve lymphocyte recovery should be investigated.

Neutrophil to Lymphocyte Ratio (NTLR) Predicts Local Control Failure and Overall Survival after Stereotactic Body Radiotherapy (SBRT) In Metastatic Sarcoma.

The neutrophil to lymphocyte ratio (NTLR) and absolute lymphocyte count (ALC) recovery are prognostic across many cancers. We investigated whether NLTR predicts SBRT success or survival in a metastatic sarcoma cohort treated with SBRT from 2014 and 2020 (N = 42). Wilcox Signed Rank Test and Friedman Test compare NTLR changes with local failure vs. local control (N = 138 lesions). Cox analyses identified factors associated with overall survival. If local control was successful, NLTR change was not significant (p = 0.30). However, NLTR significantly changed in patients local failure (p = 0.027). The multivariable Cox model demonstrated higher NLTR before SBRT was associated with worse overall survival (p = 0.002). The optimal NTLR cut point was 5 (Youden index: 0.418). One-year overall survival in SBRT metastatic sarcoma cohort was 47.6% (CI 34.3%-66.1%). Patients with an NTLR above 5 had a one-year overall survival of 37.7% (21.4%-66.3%); patients with an NTLR below 5 had a significantly improved overall survival of 63% (43.3%-91.6%, p = 0.014). Since NTLR at the time of SBRT was significantly associated with local control success and overall survival in metastatic sarcoma treated with SBRT, future efforts to reduce tumor inhibitory microenvironment factors and improved lymphocyte recovery should be investigated.

Clinical Nomogram Using Novel Computed Tomography-Based Radiomics Predicts Survival in Patients With Non-Small-Cell Lung Cancer Treated With Stereotactic Body Radiation Therapy.

PURPOSE: Improved survival prediction and risk stratification in non-small-cell lung cancer (NSCLC) would lead to better prognosis counseling, adjuvant therapy selection, and clinical trial design. We propose the persistent homology (PHOM) score, the radiomic quantification of solid tumor topology, as a solution. MATERIALS AND METHODS: Patients diagnosed with stage I or II NSCLC primarily treated with stereotactic body radiation therapy (SBRT) were selected (N = 554). The PHOM score was calculated for each patient's pretreatment computed tomography scan (October 2008-November 2019). PHOM score, age, sex, stage, Karnofsky Performance Status, Charlson Comorbidity Index, and post-SBRT chemotherapy were predictors in the Cox proportional hazards models for OS and cancer-specific survival. Patients were split into high- and low-PHOM score groups and compared using Kaplan-Meier curves for overall survival (OS) and cumulative incidence curves for cause-specific death. Finally, we generated a validated nomogram to predict OS, which is publicly available at Eashwarsoma.Shinyapps. RESULTS: PHOM score was a significant predictor for OS (hazard ratio [HR], 1.17; 95% CI, 1.07 to 1.28) and was the only significant predictor for cancer-specific survival (1.31; 95% CI, 1.11 to 1.56) in the multivariable Cox model. The median survival for the high-PHOM group was 29.2 months (95% CI, 23.6 to 34.3), which was significantly worse compared with the low-PHOM group (45.4 months; 95% CI, 40.1 to 51.8; P < .001). The high-PHOM group had a significantly greater chance of cancer-specific death at post-treatment month 65 (0.244; 95% CI, 0.192 to 0.296) compared with the low-PHOM group (0.171; 95% CI, 0.123 to 0.218; P = .029). CONCLUSION: The PHOM score is associated with cancer-specific survival and predictive of OS. Our developed nomogram can be used to inform clinical prognosis and assist in making post-SBRT treatment considerations.

Association between biologically effective dose and local control after stereotactic body radiotherapy for metastatic sarcoma.

Introduction: Stereotactic body radiation therapy (SBRT) is increasingly utilized for patients with recurrent and metastatic sarcoma. SBRT affords the potential to overcome the relative radioresistance of sarcomas through delivery of a focused high biological effective dose (BED) as an alternative to invasive surgery. We report local control outcomes after metastatic sarcoma SBRT based on radiation dose and histology. Methods: From our IRB-approved single-institution registry, all patients treated with SBRT for metastatic sarcoma between 2014 and 2020 were identified. Kaplan-Meier analysis was used to estimate local control and overall survival at 1 and 2 years. A receiver operating characteristic (ROC) curve was generated to determine optimal BED using an α/ß ratio of 3. Local control was compared by SBRT dose using the BED cut point and evaluated by histology. Results: Forty-two patients with a total of 138 lesions met inclusion criteria. Median imaging follow up was 7.73 months (range 0.5-35.0). Patients were heavily pre-treated with systemic therapy. Median SBRT prescription was 116.70 Gy BED (range 66.70-419.30). Desmoplastic small round cell tumor, Ewing sarcoma, rhabdomyosarcoma, and small round blue cell sarcomas were classified as radiosensitive (n = 63), and all other histologies were classified as radioresistant (n = 75). Local control for all lesions was 66.7% (95% CI, 56.6-78.5) at 1 year and 50.2% (95% CI, 38.2-66.1) at 2 years. Stratifying by histology, 1- and 2-year local control rates were 65.3% and 55.0%, respectively, for radiosensitive, and 68.6% and 44.5%, respectively, for radioresistant histologies (p = 0.49). The ROC cut point for BED was 95 Gy. Local control rates at 1- and 2-years were 75% and 61.6%, respectively, for lesions receiving >95 Gy BED, and 46.2% and 0%, respectively, for lesions receiving <95 Gy BED (p = 0.01). On subgroup analysis, local control by BED > 95 Gy was significant for radiosensitive histologies (p = 0.013), and trended toward significance for radioresistant histologies (p = 0.25). Conclusion: There is a significant local control benefit for sarcoma SBRT when a BED > 95 Gy is used. Further investigation into the dose-response relationship is warranted to maximize the therapeutic index.

Independently validated sex-specific nomograms for predicting survival in patients with newly diagnosed glioblastoma: NRG Oncology RTOG 0525 and 0825.

BACKGROUND/PURPOSE: Glioblastoma (GBM) is the most common primary malignant brain tumor. Sex has been shown to be an important prognostic factor for GBM. The purpose of this study was to develop and independently validate sex-specific nomograms for estimation of individualized GBM survival probabilities using data from 2 independent NRG Oncology clinical trials. METHODS: This analysis included information on 752 (NRG/RTOG 0525) and 599 (NRG/RTOG 0825) patients with newly diagnosed GBM. The Cox proportional hazard models by sex were developed using NRG/RTOG 0525 and significant variables were identified using a backward selection procedure. The final selected models by sex were then independently validated using NRG/RTOG 0825. RESULTS: Final nomograms were built by sex. Age at diagnosis, KPS, MGMT promoter methylation and location of tumor were common significant predictors of survival for both sexes. For both sexes, tumors in the frontal lobes had significantly better survival than tumors of multiple sites. Extent of resection, and use of corticosteroids were significant predictors of survival for males. CONCLUSIONS: A sex specific nomogram that assesses individualized survival probabilities (6-, 12- and 24-months) for patients with GBM could be more useful than estimation of overall survival as there are factors that differ between males and females. A user friendly online application can be found here- https://npatilshinyappcalculator.shinyapps.io/SexDifferencesInGBM/ .

Persistent homology of tumor CT scans is associated with survival in lung cancer.

PURPOSE: Radiomics, the objective study of nonvisual features in clinical imaging, has been useful in informing decisions in clinical oncology. However, radiomics currently lacks the ability to characterize the overall topological structure of the data. This niche can be filled by persistent homology, a form of topological data analysis that analyzes high-level structure. We hypothesized that persistent homology features quantified using cubical complexes could be extracted from lung tumor scans and related to survival. METHODS: We obtained segmented computed tomography (CT) lung scans (n = 565) from the NSCLC-Radiomics and NSCLC-Radiogenomics datasets in The Cancer Imaging Archive. These scans are three-dimensional images whose pixel intensity corresponds to a number of Hounsfield units. Cubical complexes are a topological image analysis method that effectively analyzes the number of topological features in an image as the image is thresholded at different intensities. We calculated a novel output called a feature curve by plotting the number of zero-dimensional (0D) topological features counted from the cubical complex filtration against each Hounsfield value. This curve's first moment of distribution was utilized as a summary statistic to show association with survival in a Cox proportional hazards model. We hypothesized that persistent homology features quantified using cubical complexes could be extracted from lung tumor scans and related to survival. RESULTS: After controlling for tumor image size, age, and stage, the first moment of the 0D topological feature curve was associated with poorer survival (HR = 1.118; 95% CI = 1.026-1.218; p = 0.01). The patients in our study with the lowest first moment scores had significantly better survival (1238 days; 95% CI = 936-1599) compared to the patients with the highest first moment scores (429 days; 95% CI = 326-601; p = 0.0015). CONCLUSIONS: We have shown that persistent homology can generate useful clinical correlates from tumor CT scans. Our 0D topological feature curve statistic predicts survival in lung cancer patients. This novel statistic may be used in tandem with standard radiomics variables to better inform clinical oncology decisions.

Treatment and surgical factors associated with longer-term glioblastoma survival: a National Cancer Database study.

BACKGROUND: Insufficient data exist to characterize factors associated with longer-term survival of glioblastoma (GBM). A population-based analysis of GBM longer-term survivors (LTS) in the United States was conducted to investigate the association between treatment, demographic, surgical factors, and longer-term survival. METHODS: From the National Cancer Database, GBM patients were identified using ICD-O-3 histology codes 9440-9442/3, 2005-2015 and were divided into routine (≤3 years) and longer-term (>3 years) overall survival (OS) groups. Univariable and multivariable logistic regression analysis was used to assess factors associated with longer-term survival. A subset analysis was performed to further investigate the association of extent of resection and treatment combinations on OS outcomes. RESULTS: A total of 93 036 patients with GBM met study criteria. Among these patients, 8484 were LTS and 84 552 were routine survivors (RS). When comparing LTS (OS of >3 years) with RS (OS of ≤3 years), younger age, insured status, metro/urban residence, treatment at academic facility, and fewer comorbidities were associated with longer-term survival. In addition, trimodality therapy (chemotherapy + radiation + surgery) was associated with having best odds of longer-term survival (odds ratio = 4.89, 95% confidence interval [3.58, 6.68]); 74% of LTS received such therapy compared with 51% of RS. Subset analysis revealed that total resection is only associated with longer-term survival status for those receiving trimodality therapy or surgery only. CONCLUSIONS: In a population-based analysis, standard of care surgery and chemo radiation connote a survival advantage in GBM. Among those receiving standard of care, having a total resection is most beneficial for longer-term survival status.