Publications by authors named "Thomas J Quinn"

40 Publications

Dynamic lung compliance imaging from 4DCT-derived volume change estimation.

Phys Med Biol 2021 Sep 24. Epub 2021 Sep 24.

Department of Radiation Oncology, Beaumont Health Research Institute, 3601 W. Thirteen Mile Road, Royal Oak, Michigan, 48073, UNITED STATES.

Background: Lung compliance is the ability of the lung to expand with changes in pressure and is one of the earliest physiological measurements to be altered in patients with parenchymal lung disease. Therefore, compliance monitoring could potentially identify patients at risk for disease progression. However, in clinical practice, compliance measurements are prohibitively invasive for use as a routine monitoring tool.

Purpose: We propose a novel method for computing dynamic lung compliance imaging (LCI) from non-contrast computed tomography (CT) scans. LCI applies image processing methods to free-breathing 4DCT images, acquired under two different continuous positive airway pressures (CPAP) applied using a full-face mask, in order to compute the lung volume change induced by the pressure change. LCI provides a quantitative volumetric map of lung stiffness.

Methods: We compared mean LCI values computed for 10 patients with idiopathic pulmonary fibrosis (IPF) and 7 non-IPF patients who were screened for lung nodules. 4DCTs were acquired for each patient at 5cm and 10 cm H20 CPAP, as the patients were free breathing at functional residual capacity. LCI was computed from the two 4DCTs. Mean LCI intensities, which represent relative voxel volume change induced by the change in CPAP pressure, were computed.

Results: The mean LCI values for patients with IPF ranged between [0.0309, 0.1165], whereas the values ranged between [0.0704, 0.2185] for the lung nodule cohort. Two-sided Wilcoxon rank sum test indicated that the difference in medians is statistically significant (p value = 0.009) and that LCI -measured compliance is overall lower in the IPF patient cohort.

Conclusion: There is considerable difference in lung compliance scores between patients with IPF compared to controls. Future longitudinal studies should look for LC alterations in areas of lung prior to radiographic detection of fibrosis to further characterize LCI's potential utility as an image marker for disease progression.
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http://dx.doi.org/10.1088/1361-6560/ac29ceDOI Listing
September 2021

Adjuvant radiotherapy improves overall survival when added to surgery and chemotherapy for uterine carcinosarcoma: a surveillance, epidemiology, and end results analysis.

Int J Clin Oncol 2021 Aug 24. Epub 2021 Aug 24.

Department of Radiation Oncology, Beaumont Hospital, 3601 W 13 Mile Rd, Royal Oak, MI, 48073, USA.

Background: Uterine carcinosarcoma (UCS) confers a high recurrence risk following surgery, and adjuvant chemotherapy (CHT) is typically administered in all stages. The benefit of radiation therapy (RT) in UCS, when added to adjuvant CHT, is unknown. We sought to analyze the Surveillance, Epidemiology, and End Results (SEER) database to ascertain whether RT improves overall survival (OS) when added to surgery and CHT for UCS.

Methods: SEER 18 Custom Data registries (Nov 2018 submission) were queried for uterine (ICD10 C54.1-9, C55.9) carcinosarcoma (ICD-0-3 8980-3). Patients with stage I-III UCS who underwent surgery and CHT ± RT were analyzed with univariate analysis (UVA) and multivariable analysis (MVA) using Kaplan-Meier and Cox proportional hazards regression modeling. Propensity-score matched analysis with inverse probability of treatment weighting (IPTW) was performed to account for indication bias. Furthermore, conditional landmark analysis (minimum three-month follow-up) was performed to minimize immortal time bias.

Results: All 1541 patients (1988-2016) underwent surgery and CHT and 54% received RT. On UVA, RT improved median and 5-year OS from 41 to 87 months and 43-55%, respectively (HR 0.65, 95% CI 0.56-0.77) (p < 0.001). After IPTW adjustment, RT improved median and 5-year OS from 46 to 65 months and 46-53%, respectively (HR 0.74, 95% CI 0.63-0.87) (p < 0.001). The benefit of RT remained on unadjusted and adjusted MVA and conditional landmark analysis.

Conclusion: In stage I-III UCS treated with surgery and CHT, receipt of RT is associated with OS benefit. Further prospective data are needed to investigate the RT's benefit in UCS.
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http://dx.doi.org/10.1007/s10147-021-02007-6DOI Listing
August 2021

Primary Parotid Tumor Thrombosis: Immunohistologic Features and Awareness of Metastatic Potential.

Cureus 2021 Jul 4;13(7):e16174. Epub 2021 Jul 4.

Department of Radiation Oncology, Beaumont Health, Royal Oak, USA.

Tumor thrombosis is a poor prognostic feature and an exceptionally rare occurrence in salivary gland malignancies. We present a case of primary parotid myoepithelial carcinoma (MC) with tumor thrombosis in the external jugular vein (EJV). An 82-year-old man presented with a right-sided facial mass. MRI with and without gadolinium demonstrated a mass of the right parotid gland with a filling defect of the right EJV. The patient underwent right parotidectomy and selective neck dissection. Tumor thrombosis was found intraoperatively within the EJV. Final pathology demonstrated a poorly differentiated MC. Adjuvant radiation therapy without concurrent systemic therapy was administered. Three months later, restaging positron emission tomography (PET) with CT revealed numerous bilateral pulmonary nodules with biopsy, demonstrating poorly differentiated MC without locoregional relapse. Given that primary parotid tumor thrombosis is associated with a poor prognosis, the use of early systemic therapy should be investigated.
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http://dx.doi.org/10.7759/cureus.16174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336355PMC
July 2021

Synthetic pulmonary perfusion images from 4DCT for functional avoidance using deep learning.

Phys Med Biol 2021 08 23;66(17). Epub 2021 Aug 23.

Beaumont Artificial Intelligence Research Laboratory, Beaumont Health, Royal Oak, MI, United States of America.

To develop and evaluate the performance of a deep learning model to generate synthetic pulmonary perfusion images from clinical 4DCT images for patients undergoing radiotherapy for lung cancer.. A clinical data set of 58 pre- and post-radiotherapyTc-labeled MAA-SPECT perfusion studies (32 patients) each with contemporaneous 4DCT studies was collected. Using the inhale and exhale phases of the 4DCT, a 3D-residual network was trained to create synthetic perfusion images utilizing the MAA-SPECT as ground truth. The training process was repeated for a 50-imaging study, five-fold validation with twenty model instances trained per fold. The highest performing model instance from each fold was selected for inference upon the eight-study test set. A manual lung segmentation was used to compute correlation metrics constrained to the voxels within the lungs. From the pre-treatment test cases ( = 5), 50th percentile contours of well-perfused lung were generated from both the clinical and synthetic perfusion images and the agreement was quantified.. Across the hold-out test set, our deep learning model predicted perfusion with a Spearman correlation coefficient of 0.70 (IQR: 0.61-0.76) and a Pearson correlation coefficient of 0.66 (IQR: 0.49-0.73). The agreement of the functional avoidance contour pairs was Dice of 0.803 (IQR: 0.750-0.810) and average surface distance of 5.92 mm (IQR: 5.68-7.55).. We demonstrate that from 4DCT alone, a deep learning model can generate synthetic perfusion images with potential application in functional avoidance treatment planning.
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http://dx.doi.org/10.1088/1361-6560/ac16ecDOI Listing
August 2021

A population-based analysis of chemoradiation versus radiation alone in the definitive treatment of patients with stage I-II squamous cell carcinoma of the anus.

J Gastrointest Oncol 2021 Apr;12(2):831-844

Beaumont Health, Department of Radiation Oncology, Royal Oak, MI, USA.

Background: The optimal management of patients with stage I-II squamous cell carcinoma (SCC) of the anus is controversial. The current study evaluates the efficacy of combined chemotherapy and radiation therapy (CRT) versus radiation therapy (RT) alone in the treatment of these patients using the Surveillance, Epidemiology, and End Results (SEER) registries.

Methods: SEER 18 Custom Data registries were queried for patients with stage I-II SCC of the anus. Univariate analysis (UVA) and multivariable analysis (MVA) using Kaplan-Meier and Cox proportional hazards regression modeling were performed. Propensity-score matched analysis with inverse probability of treatment weighting (IPTW) was used to account for indication bias.

Results: A total of 4,288 patients with stage I-II disease were identified, of whom 3,982 (93%) underwent CRT and 306 (7%) underwent RT. Median follow-up was 42 months. Approximately 30.8% had T1 disease and 69.2% had T2-T3 disease. The IPTW-adjusted 5-year overall survival (OS) was 76.7%, with no significant differences between the CRT and RT groups (77% 73.5%, P=0.33). On multivariate IPTW-adjusted analysis, the lack of association between CRT use and OS was upheld (HR, 0.84, 95% CI, 0.65-1.08, P=0.2). On subgroup analyses, 5-year OS was 86% with CRT (n=1,216) and 84.2% with RT (n=103) (P=0.74) in stage I (T1N0) patients, while 5-year OS was 72.8% with CRT (n=2,766) and 66.4% with RT (n=203) (P=0.13) in stage II (T2-3N0) patients. CRT was associated with improved median OS in stage II patients (119 months not reached, P=0.04).

Conclusions: The current study suggests that omission of concurrent chemotherapy is not associated with inferior OS in patients with stage I SCC of the anus. However, combined chemoradiation was superior to radiation alone in patients with stage II disease. Prospective evidence is needed to optimize clinical decision-making in this patient population.
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http://dx.doi.org/10.21037/jgo-20-530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107581PMC
April 2021

The role of chemotherapy in the management of olfactory neuroblastoma: A 40-year surveillance, epidemiology, and end results registry study.

Health Sci Rep 2021 Jun 2;4(2):e257. Epub 2021 May 2.

Department of Radiation Oncology Beaumont Health Royal Oak Michigan.

Background: In this retrospective surveillance, epidemiology, and end results (SEER) registry analysis, we investigated the role of chemotherapy (CT) in the treatment of olfactory neuroblastoma (ON), an exceedingly rare sino-nasal tumor typically treated with surgery and/or radiation therapy (RT).

Methods: We analyzed all patients in the SEER registry diagnosed with a single primary malignancy of ON, a primary tumor site within the nasal cavity or surrounding sinuses, sufficient staging information to derive Kadish staging, and >0 days of survival, ensuring follow-up data. Receipt of CT in the SEER registry was documented as either Yes or No/Unknown.

Results: Six hundred and thirty-six patients were identified. One hundred and ninety-five patients received CT as part of their treatment for ON. Following propensity score matching and inverse probability of treatment weighting, there was inferior overall survival (OS) (HR 1.7, 95% CI: 1.3-2.2, = .001) and cancer-specific survival (CSS) (HR 1.8, 95% CI: 1.3-2.4,  < .001) for patients who received CT compared to those who were not treated with CT or had unknown CT status. On subgroup analysis, the only patient population that derived benefit from CT were patients who did not receive surgery and were treated with CT and/or RT (HR 0.3, 95% CI: 0.14-0.61,  < .001).

Conclusions: Based on this retrospective SEER registry analysis, the use of CT in the management of ON is associated with decreased OS. Our analysis suggests that patients who are considered nonsurgical candidates may benefit from the addition of CT.
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http://dx.doi.org/10.1002/hsr2.257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088587PMC
June 2021

Higher biologically effective dose is associated with improved survival in patients with squamous cell carcinoma of the lung treated with stereotactic body radiation therapy.

Radiother Oncol 2021 07 21;160:25-31. Epub 2021 Apr 21.

Beaumont Health, Department of Radiation Oncology, Royal Oak, United States.

Background: Multiple studies have suggested that patients with early-stage SCC of the lung treated with SBRT are more susceptible to local failure compared to other NSCLC histologies. It is unknown if higher BED leads to improved outcomes in this patient population. We evaluated the effect of "high" BED versus "low" BED SBRT on overall survival (OS) in SCC and non-SCC NSCLC patients.

Methods: The National Cancer Database was used to identify patients with cT1-2N0M0 NSCLC diagnosed between 2006-2016 treated with 3-5 fraction SBRT. Patients were grouped by BED (>150 Gy) and BED (≤132 Gy). Univariate and multivariable analysis using Kaplan-Meier and Cox proportional hazards regression modeling were performed. Propensity-score matched analysis with inverse probability of treatment (IPTW) weighting was used to account for selection bias.

Results: We identified 4,717 eligible SCC patients and 8,807 eligible non-SCC NSCLC patients. In SCC patients, BED was associated with improved OS in both univariate and multivariate analysis (MVA HR 0.84 95% CI 0.76-0.92, p < 0.001), with estimated IPTW-adjusted 3-year OS of 49% compared to 41% for the BED group. In contrast, BED was not associated with improved OS compared to BED for non-SCC NSCLC patients (MVA HR 0.94 95% CI 0.86-1.04, p = 0.23), with estimated IPTW-adjusted 3-year OS of 54% and 53%, respectively.

Conclusions: Our analysis suggests that in patients with early-stage NSCLC, SBRT regimens with BED > 150 Gy may confer a survival benefit in patients with SCC histology. Histology-based dose modification should be considered, and prospective validation may be warranted.
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http://dx.doi.org/10.1016/j.radonc.2021.04.010DOI Listing
July 2021

Ethical Allocation of Proton Therapy and the Insurance Review Process.

Pract Radiat Oncol 2021 Sep-Oct;11(5):e449-e458. Epub 2021 Feb 3.

Department of Radiation Oncology, Beaumont Health, Royal Oak, Michigan; Oakland University William Beaumont School of Medicine, Rochester, Michigan. Electronic address:

Purpose: The purpose of this study was to delineate a scoring system to maximize the ethical allocation of proton beam therapy (PBT) and determine what factors are associated with receipt of PBT, including the role of specific insurance providers.

Methods And Materials: Our scoring system was developed in collaboration with a multidisciplinary panel of experts. Patients submitted for PBT consideration were assigned a score by committee at a weekly peer-reviewed session at a time when our center was operating at capacity. Univariate analysis and multivariable analysis of initial and final insurance response were performed.

Results: One hundred ninety-seven patients were prospectively reviewed. Ninety-three percent of patients with Medicaid coverage, 88% of patients with Medicare, and 78% of patients with private insurance were ultimately approved for PBT. Median time to final insurance response was 12 days (interquartile range, 9-18 days) for patients who were ultimately denied PBT coverage. Having primary provider C (odds ratio [OR], 14; 95% confidence interval [CI], 1.20-1.96; P = .033) or third party providers A (OR, 4.22; 95% CI, 1.71-10.9; P = .002) or B (OR, 5.28; 95% CI, 1.56-17.2; P = .006) was significantly associated with final insurance denial for PBT on univariate analysis. Total score (OR, 0.79; 95% CI, 0.67-0.90; P = .002) and having coverage through third party provider A (OR, 24.2; 95% CI, 9.51-68.9; P < .001) were associated with final insurance response on multivariable analysis.

Conclusions: Our scoring system was significantly associated with receipt of proton beam therapy. Certain insurance providers are less likely to approve PBT for patients, all else being equal. Such a scoring system could be implemented effectively at other PBT facilities, and additional work is needed in ensuring patients with the most to gain from PBT will be approved by their insurance providers.
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http://dx.doi.org/10.1016/j.prro.2021.01.007DOI Listing
September 2021

Inhibition of Colony-Stimulating Factor-1 Receptor Enhances the Efficacy of Radiotherapy and Reduces Immune Suppression in Glioblastoma.

In Vivo 2021 Jan-Feb;35(1):119-129

Department of Radiation Oncology, Beaumont Health, Royal Oak, MI, U.S.A.;

Aim: To use inhibition of colony-stimulating factor-1 receptor (CSF-1R) to target tumor-associated macrophages (TAMs) and improve the efficacy of radiotherapy in glioblastoma (GBM).

Materials And Methods: The CSF-1R inhibitor BLZ-945 was used to examine the impact of CSF-1R inhibition on M2 polarization in vitro. Using an orthotopic, immunocompetent GBM model, mice were treated with vehicle, RT, BLZ-945, or RT plus BLZ-945.

Results: BLZ-945 reduced M2 polarization in vitro. BLZ-945 alone did not improve median overall survival (mOS=29 days) compared to control mice (mOS=27 days). RT improved survival (mOS=45 days; p=0.02), while RT plus BLZ-945 led to the longest survival (mOS=not reached; p=0.005). Resected tumors had a relatively large population of M2 TAMs in GBM at baseline, which was increased in response to RT. BLZ-945 reduced RT-induced M2 infiltration.

Conclusion: Inhibition of CSF-1R improved response to RT in the treatment of GBM and may represent a promising strategy to improve RT-induced antitumor immune responses.
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http://dx.doi.org/10.21873/invivo.12239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880776PMC
June 2021

Usefulness of Coronary Computed Tomographic Angiography to Evaluate Coronary Artery Disease in Radiotherapy-Treated Breast Cancer Survivors.

Am J Cardiol 2021 03 4;143:14-20. Epub 2021 Jan 4.

Beaumont Hospital, Division of Cardiology, Royal Oak, Michigan.

Breast cancer is the most commonly diagnosed cancer in women and radiotherapy is a widely used treatment approach. However, there is an increased risk of coronary artery disease and cardiac death in women treated with radiotherapy. The present study was undertaken to clarify the relation between radiotherapy and coronary disease in women with previous breast irradiation using coronary computed tomographic angiography (CCTA). We conducted a retrospective analysis of women with a history of right or left-sided breast cancer (RBC; LBC) treated with radiotherapy who subsequently underwent CCTA. RBC patients who had reduced radiation doses to the myocardium served as controls. Patients (n = 6,593) with a history of nonmetastatic breast cancer treated with radiotherapy were screened for completion of CCTA; 49 LBC and 45 RBC women were identified. Age and risk factor matched patients with LBC had higher rates of coronary disease compared with RBC patients; left anterior descending (LAD) coronary artery (76% vs 31% [p < 0.001]), left circumflex (33% vs. 6.7% [p = 0.004]), and right coronary artery (37% vs 13% [p = 0.018]). Mean LAD radiation dose and mean heart dose strongly correlated with coronary disease, with a 21% higher incidence of disease in the LAD per Gy for mean LAD dose and a 95% higher incidence of disease in the LAD per Gy for mean heart dose. In conclusion, LBC patients treated with radiotherapy have a significantly higher incidence of coronary disease when compared with a matched group of patients treated for RBC. Radiation doses correlated with the incidence of coronary disease.
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http://dx.doi.org/10.1016/j.amjcard.2020.12.038DOI Listing
March 2021

Rectal cancer in young patients: incidence and outcome disparities.

J Gastrointest Oncol 2020 Oct;11(5):880-893

Department of Radiation Oncology, Beaumont Health, Royal Oak, MI, USA.

Background: There is an alarming rise in incidence among young patients with rectal cancer. The National Cancer Database (NCDB) and Surveillance, Epidemiology, and End Results Analysis (SEER) databases may help identify population level disparities in incidence and cancer-related outcomes.

Methods: A total of 197,178 patients within the SEER 18 registry and 221,886 patients from the NCDB database with rectal cancer were evaluated in this retrospective cohort study. The analyzed cohort consisted of young (<50), white or African American patients. Indication bias was mitigated by conducting inverse probability of treatment weighted analysis using binary logistic regression modeling to determine propensity score for being white or African American.

Results: A total of 6,144 young patients were identified from the SEER 18 registry and a total of 17,819 young patients were identified from the NCDB. From 1990 to 2016, there was a significant change in rectal cancer incidence, with a steadily increasing APC of 3.06 (P<0.05). The was no overall change in age-adjusted APC among young African American patients (APC 0.00, P=1); however, there was a significant increase among young white patients (APC 2.97, P<0.05). There was an increased incidence for both stage III and IV among young rectal cancer patients, with an age-adjusted APC of 5.35 and 3.83, respectively (P<0.05). After propensity score matching and inverse probability of treatment weighting, young African Americans had worse overall survival in both the NCDB and SEER (HR 1.1-1.3, P<0.05) databases. This disparity was also seen for cancer-specific survival (HR 1.5, P=0.002).

Conclusions: The current study adds to the growing body of literature demonstrating an alarming increase in incidence of rectal cancer among young patients. Moreover, the incidence appears to be increasing particularly among young white patients and driven by stage III disease.
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http://dx.doi.org/10.21037/jgo-20-197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657826PMC
October 2020

Left anterior descending artery avoidance in patients receiving breast irradiation.

Med Dosim 2021 Spring;46(1):57-64. Epub 2020 Sep 2.

Department of Radiation Oncology, Beaumont Health System, Royal Oak, MI 48073, USA. Electronic address:

Purpose: Dose to the left anterior descending artery (LAD) may be significant in patients receiving left-sided irradiation for breast cancer. We investigated if prospective contouring and avoidance of the LAD during treatment planning were associated with lower LAD dose.

Methods And Materials: We reviewed dosimetric plans for 323 patients who received left whole breast or chest wall irradiation with or without internal mammary node (IMLN) coverage between 1/2014 and 1/2019 at a single institution. The LAD was contoured prospectively for 155 cases, and techniques were utilized to minimize LAD dose. Dose-volume-histograms from these patients were compared to those of 168 patients for whom the LAD was contoured retrospectively after treatment completion. EQD2 was calculated to account for fractionation differences.

Results: Compared to cases where the LAD was contoured retrospectively (n = 126), prospective LAD contouring (n = 124) was associated with lower unadjusted median max and mean LAD doses for 250 patients receiving whole-breast irradiation (WBI) without IMLN coverage: 8.5 Gy vs 5.2 Gy (p < 0.0001) and 3.6 Gy vs 2.7 Gy (p < 0.0001), respectively. EQD2 median max and mean LAD doses were also lower with prospective LAD contouring: 5.2 Gy vs 3.0 Gy (p < 0.0001) and 1.9 Gy vs 1.5 Gy (p < 0.0001), respectively. Compared to cases where the LAD was contoured retrospectively (n = 42), prospective LAD contouring (n = 31) was associated with lower max LAD doses for 73 patients with IMLN coverage: 20.4 Gy vs 14.3 Gy (p = 0.042). There was a nonsignificant reduction in median mean LAD dose: 6.2 Gy vs 6.1 Gy (p = 0.33). LAD doses were reduced while maintaining IMLN coverage (mean V90% >90%).

Conclusions: Prospective contouring and avoidance of the LAD were associated with lower max and mean LAD doses in patients receiving WBI and with lower max LAD doses in patients receiving IMLN treatment. Further reduction in LAD dose may require stricter optimization weighting or compromise in IMLN coverage.
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http://dx.doi.org/10.1016/j.meddos.2020.07.006DOI Listing
September 2020

The Role of Postoperative Radiation Therapy for pN2 Non-small-cell Lung Cancer.

Clin Lung Cancer 2021 01 30;22(1):e5-e17. Epub 2020 Jul 30.

Department of Radiation Oncology, Beaumont Health, Royal Oak, MI. Electronic address:

Background: The role for postoperative radiation therapy (PORT) for patients with non-small-cell lung cancer (NSCLC) with mediastinal lymph node (LN) involvement (pN2 disease) is controversial. We compared surgery alone with PORT among patients with pN2 NSCLC. We then performed subset analyses to better delineate patients that might benefit from PORT.

Patients And Methods: We conducted a propensity score (PS)-matched, inverse probability of treatment weighting (IPTW) Surveillance, Epidemiology, and End Results (SEER) analysis of patients with pN2 disease from 1989 to 2016 with surgery alone or PORT. Multiple imputation with chained equations was used for missing LN data.

Results: A total of 8631 patients were included in this analysis; 4579 underwent surgery alone, and 4052 underwent PORT. Following PS matching and IPTW, there was no difference in overall survival (OS) (hazard ratio [HR], 0.99; P = .76). However, PORT improved OS among a subset of patients with a LN positive to sampled ratio ≥ 50% (HR, 0.90; P = .01). Moreover, there was a trend towards improved OS among this subset, even with chemotherapy (HR, 0.91; P = .09).

Conclusion: PORT is not associated with an improvement or detriment in OS for all patients with pN2 NSCLC. However, patients with a positive to sampled LN ratio ≥ 50% may benefit, regardless of chemotherapy status. Nevertheless, PORT will remain the standard of care as we await the results of the ongoing LUNG ART trial.
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http://dx.doi.org/10.1016/j.cllc.2020.07.008DOI Listing
January 2021

Omission of Axillary Lymph Node Dissection is Associated with Inferior Survival in Breast Cancer Patients with Residual N1 Nodal Disease Following Neoadjuvant Chemotherapy.

Ann Surg Oncol 2021 Feb 25;28(2):930-940. Epub 2020 Jul 25.

Department of Radiation Oncology, Beaumont Health, Royal Oak, MI, USA.

Background: The appropriateness of substituting sentinel lymph node dissection (SLND) and regional nodal irradiation (RNI) for axillary lymph node dissection (ALND) in patients with residual lymph node (LN) disease following neoadjuvant chemotherapy (NAC) is unknown. We used the National Cancer Database (NCDB) to compare survival following SLND and ALND in breast cancer patients with residual LN disease.

Methods: We analyzed NCDB patients, treated between 2006 and 2014, with cT1-3, cN1, cM0 breast cancer and residual disease in 1-3 axillary LNs (ypN1) following NAC. Patients were grouped into those who received SLND (defined as removal of ≤ 4 LNs) and RNI, or ALND and RNI. Patients were matched for all patient, tumor, and treatment characteristics.

Results: We identified 1313 eligible patients in the ALND group and 304 patients in the SLND group. For the matched cohorts, SLND was associated with significantly lower survival in both univariate and doubly robust multivariable analyses (MVA) (HR 1.7, 95% CI 1.3-2.2, P < 0.001 for MVA), with estimated 5-year OS of 71%, compared with 77% in the ALND group (P = 0.01). Exploratory subgroup analyses showed that SLND was comparable with ALND in patients with luminal A or B tumors with a single metastatic LN (HR 1.03, 95% CI 0.59-1.8, (P = 0.91).

Conclusions: Our analysis suggests that, while an ALND may not be needed for patients with limited residual nodal burden and biologically favorable tumors, SLND should not be routinely substituted for ALND in patients with ypN1 disease following NAC until its efficacy is confirmed by prospective trials.
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http://dx.doi.org/10.1245/s10434-020-08928-2DOI Listing
February 2021

Pulsed radiation therapy for the treatment of newly diagnosed glioblastoma.

Neuro Oncol 2021 03;23(3):447-456

Oakland University William Beaumont School of Medicine, Auburn Hills, Michigan.

Background: Pulsed radiation therapy (PRT) has shown effective tumor control and superior normal-tissue sparing ability compared with standard radiotherapy (SRT) in preclinical models and retrospective clinical series. This is the first prospective trial to investigate PRT in the treatment of patients with newly diagnosed glioblastoma (GBM).

Methods: This is a single-arm, prospective study. Patients with newly diagnosed GBM underwent surgery, followed by 60 Gy of PRT with concurrent temozolomide (TMZ). Each day, a 2-Gy fraction was divided into ten 0.2-Gy pulses, separated by 3-minute intervals. Patients received maintenance TMZ. Neurocognitive function (NCF) and quality of life (QoL) were monitored for 2 years using the Hopkins Verbal Learning Test‒Revised and the European Organisation for Research and Treatment of Cancer QLQ-C30 QoL questionnaire. Change in NCF was evaluated based on a minimal clinically important difference (MCID) threshold of 0.5 standard deviation.

Results: Twenty patients were enrolled with a median follow-up of 21 months. Median age was 60 years. Forty percent underwent subtotal resection, and 60% underwent gross total resection. One patient had an isocitrate dehydrogenase (IDH)-mutated tumor. Median progression-free survival (PFS) and overall survival (OS) were 10.7 and 20.9 months, respectively. In a post-hoc comparison, median OS for the prospective cohort was longer, compared with a matched cohort receiving SRT (20.9 vs 14 mo, P = 0.042). There was no decline in QoL, and changes in NCF scores did not meet the threshold of an MCID.

Conclusions: Treatment of newly diagnosed GBM with PRT is feasible and produces promising effectiveness while maintaining neurocognitive function and QoL. Validation of our results in a larger prospective trial warrants consideration.
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http://dx.doi.org/10.1093/neuonc/noaa165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992887PMC
March 2021

Deep convolutional neural networks for automatic segmentation of thoracic organs-at-risk in radiation oncology - use of non-domain transfer learning.

J Appl Clin Med Phys 2020 Jun;21(6):108-113

Beaumont Artificial Intelligence Research Laboratory, Beaumont Health System, Royal Oak, MI, USA.

Purpose: Segmentation of organs-at-risk (OARs) is an essential component of the radiation oncology workflow. Commonly segmented thoracic OARs include the heart, esophagus, spinal cord, and lungs. This study evaluated a convolutional neural network (CNN) for automatic segmentation of these OARs.

Methods: The dataset was created retrospectively from consecutive radiotherapy plans containing all five OARs of interest, including 22,411 CT slices from 168 patients. Patients were divided into training, validation, and test datasets according to a 66%/17%/17% split. We trained a modified U-Net, applying transfer learning from a VGG16 image classification model trained on ImageNet. The Dice coefficient and 95% Hausdorff distance on the test set for each organ was compared to a commercial atlas-based segmentation model using the Wilcoxon signed-rank test.

Results: On the test dataset, the median Dice coefficients for the CNN model vs. the multi-atlas model were 71% vs. 67% for the spinal cord, 96% vs. 94% for the right lung, 96%vs. 94% for the left lung, 91% vs. 85% for the heart, and 63% vs. 37% for the esophagus. The median 95% Hausdorff distances were 9.5  mm vs. 25.3 mm, 5.1  mm vs. 8.1 mm, 4.0  mm vs. 8.0 mm, 9.8  mm vs. 15.8 mm, and 9.2 mm vs. 20.0 mm for the respective organs. The results all favored the CNN model (P < 0.05).

Conclusions: A 2D CNN can achieve superior results to commercial atlas-based software for OAR segmentation utilizing non-domain transfer learning, which has potential utility for quality assurance and expediting patient care.
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http://dx.doi.org/10.1002/acm2.12871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324695PMC
June 2020

Addition of radiotherapy to surgery and chemotherapy improves survival in localized malignant pleural mesothelioma: A Surveillance, Epidemiology, and End Results (SEER) study.

Lung Cancer 2020 08 30;146:120-126. Epub 2020 May 30.

Department of Radiation Oncology, Beaumont Health, 3601 W 13 Mile Rd, Royal Oak, MI 48073, United States. Electronic address:

Introduction: Malignant pleural mesothelioma (MPM) is a devastating disease with poor survival outcomes for most patients. Optimizing therapeutic approaches is thus vital, but has been hampered by a dearth of randomized trials to guide decision making. We used a population-level database to evaluate the impact of radiotherapy as a component of trimodality therapy on overall survival (OS) in MPM.

Methods: We retrospectively reviewed the SEER Radiation/Chemotherapy database for patients with MPM who received surgery and chemotherapy, with or without radiotherapy. A propensity score-matched analysis with inverse probability of treatment weighting (IPTW) was performed. Weight-adjusted univariate KM analysis was performed and doubly robust, IPTW-adjusted multivariable cox proportional hazards regression modeling was also performed to quantify the effect of radiotherapy on OS in trimodality therapy for MPM.

Results: 1015 patients were identified. 678 patients received surgery and chemotherapy, and 337 patients received trimodality therapy. For patients with localized disease, OS was significantly improved with trimodality therapy (HR 0.56, CI 0.4 - 0.8, p = 0.001), which persisted with IPTW adjustment (HR 0.65, CI 0.49 - 0.95, p = 0.0248). No significant benefit was seen for patients with regional or distant disease. On multivariate analysis, positive predictors of survival after IPTW adjustment were female sex, diagnosis after 2005, and left-sided disease.

Conclusions: These findings support a significant benefit to OS by incorporating radiotherapy as a component of trimodality therapy for patients with localized MPM compared to only surgery and chemotherapy. It does not provide a significant overall survival benefit for patients with regional or metastatic disease.
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http://dx.doi.org/10.1016/j.lungcan.2020.05.032DOI Listing
August 2020

Patterns of care and outcomes for adjuvant treatment of pT3N0 rectal cancer using the National Cancer Database.

J Gastrointest Oncol 2020 Feb;11(1):1-12

Department of Radiation Oncology, Beaumont Health, Royal Oak, MI, USA.

Background: The standard of care in locally advanced rectal cancer is preoperative chemoradiation followed by surgical resection. However, the optimal treatment paradigm is currently controversial for patients with pathological T3N0 (pT3N0) in the era of total mesorectal excision (TME). Given the paucity of data, we conducted an analysis using the National Cancer Database (NCDB) to identify patterns of care and outcomes.

Methods: We utilized the NCDB to identify 7,836 non-metastatic, pT3N0 rectal cancer patients who did not receive neoadjuvant therapy from 2004-2014. Univariate and multivariable analysis for factors affecting treatment selection were completed using logistic regression. Overall survival (OS) analyses were completed using Cox regression modeling, incorporating propensity scores with inverse probability of treatment weighting (IPTW) and conditional landmark analysis.

Results: There was a significant improvement in OS in patients receiving adjuvant chemotherapy (P<0.01) or radiotherapy (RT) with chemotherapy (P<0.01) observation alone. There was no significant difference between RT observation (P=0.54) and chemotherapy chemotherapy with RT cohorts (P=0.15). Multivariable analysis showed age, gender, race, insurance status, income, Charlson-Deyo Comorbidity Condition (CDCC) score, facility location, grade, surgical margin, RT, and chemotherapy to be statistically significant predictors of OS. After correcting for indication and immortal time biases, chemotherapy, with or without RT, improved OS compared with observation [hazard ratio (HR) 0.48, P<0.001]. This benefit was maintained in the margin negative cohort.

Conclusions: Practice patterns vary in the management of pT3N0 rectal cancer patients. This analysis suggests that the use of adjuvant therapy, particularly adjuvant chemotherapy with or without RT, appears to improve OS.
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http://dx.doi.org/10.21037/jgo.2019.10.02DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052766PMC
February 2020

Post-mastectomy radiotherapy is associated with improved overall survival in T3N0 patients who do not receive chemotherapy.

Radiother Oncol 2020 04 14;145:229-237. Epub 2020 Feb 14.

Department of Radiation Oncology, Beaumont Health, Royal Oak, MI, United States. Electronic address:

Background And Purpose: There is limited retrospective evidence addressing the utility of post-mastectomy radiotherapy (PMRT) in patients with T3N0 breast cancer. We performed a retrospective analysis of the National Cancer Database (NCDB) comparing overall survival (OS) in T3N0 patients treated with mastectomy alone (MTX) or with PMRT.

Materials And Methods: We performed a matched-cohort analysis of NCDB breast cancer patients with pT3N0 disease who did not receive NAC, or cT3N0 patients who received NAC treated between 2006 and 2014. Patients were matched for all available baseline characteristics using propensity scores with inverse probability of treatment weighting (IPTW) with stabilized weights.

Results: We identified 13,901 eligible patients. In the pT3N0 cohort, median follow-up was 47 months for the MTX group and 50 months for the PMRT group. In the cT3N0 cohort, median follow-up was 44 months for the MTX group and 46 months for the PMRT group. OS was higher in pT3N0 patients treated with PMRT compared to MTX: 7-year OS of 74% vs. 65% (P < 0.001). Doubly robust multivariable analysis showed an association between PMRT and improved OS (HR 0.78, 95% CI 0.68-0.89, P < 0.001). There was no benefit to PMRT in patients who received adjuvant chemotherapy (AC). In the NAC cohort, PMRT did not change OS, with 7-year OS of 78% with MTX and 79% with PMRT. There was a trend of improved OS with PMRT in patients with residual disease in the breast and lymph nodes (HR 0.70, 95% CI 0.46-1.07).

Conclusion: PMRT improves OS in patients with pT3N0 disease, but the benefit appears limited to those who do not receive AC. PMRT does not improve OS in patients with cT3N0 disease who receive NAC, but there might be a benefit in patients with a poor response to chemotherapy. However, longer follow-up may be needed to make a definitive conclusion about the benefit of PMRT in patients who receive chemotherapy.
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http://dx.doi.org/10.1016/j.radonc.2020.01.022DOI Listing
April 2020

Stereotactic radiosurgery for pediatric brain arteriovenous malformations: long-term outcomes.

J Neurosurg Pediatr 2020 Feb 7:1-9. Epub 2020 Feb 7.

1Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia.

Objective: Contrary to the better described obliteration- and hemorrhage-related data after stereotactic radiosurgery (SRS) of brain arteriovenous malformations (AVMs) in pediatric patients, estimates of the rarer complications, including cyst and tumor formation, are limited in the literature. The aim of the present study was to assess the long-term outcomes and risks of SRS for AVMs in pediatric patients (age < 18 years).

Methods: The authors retrospectively analyzed the International Radiosurgery Research Foundation pediatric AVM database for the years 1987 to 2018. AVM obliteration, post-SRS hemorrhage, cyst formation, and tumor formation were assessed. Cumulative probabilities, adjusted for the competing risk of death, were calculated.

Results: The study cohort comprised 539 pediatric AVM patients (mean follow-up 85.8 months). AVM obliteration was observed in 64.3% of patients, with cumulative probabilities of 63.6% (95% CI 58.8%-68.0%), 77.1% (95% CI 72.1%-81.3%), and 88.1% (95% CI 82.5%-92.0%) over 5, 10, and 15 years, respectively. Post-SRS hemorrhage was observed in 8.4% of patients, with cumulative probabilities of 4.9% (95% CI 3.1%-7.2%), 9.7% (95% CI 6.4%-13.7%), and 14.5% (95% CI 9.5%-20.5%) over 5, 10, and 15 years, respectively. Cyst formation was observed in 2.1% of patients, with cumulative probabilities of 5.5% (95% CI 2.3%-10.7%) and 6.9% (95% CI 3.1%-12.9%) over 10 and 15 years, respectively. Meningiomas were observed in 2 patients (0.4%) at 10 and 12 years after SRS, with a cumulative probability of 3.1% (95% CI 0.6%-9.7%) over 15 years.

Conclusions: AVM obliteration can be expected after SRS in the majority of the pediatric population, with a relatively low risk of hemorrhage during the latency period. Cyst and benign tumor formation after SRS can be observed in 7% and 3% of patients over 15 years, respectively. Longitudinal surveillance for delayed neoplasia is prudent despite its low incidence.
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http://dx.doi.org/10.3171/2019.12.PEDS19595DOI Listing
February 2020

Who Benefits From a Prostate Rectal Spacer? Secondary Analysis of a Phase III Trial.

Pract Radiat Oncol 2020 May - Jun;10(3):186-194. Epub 2020 Jan 21.

The Department of Radiation Oncology, Beaumont Hospital, Dearborn, Michigan. Electronic address:

Purpose: Previously a phase III trial of a hydrogel rectal spacer during prostate radiation therapy found decreased toxicity and a clinically significant improvement in bowel quality of life (QOL) at 3 years by the Expanded Prostate Cancer Index. We performed a secondary analysis to identify men less likely to benefit.

Methods And Materials: Clinical and dosimetric data for the 222 patients enrolled on the SpaceOAR phase III trial were analyzed. The volume of rectum treated to 70 Gy (V70) and the quantitative analysis of normal tissue effects in the clinic (QUANTEC) rectal dose goals were used as surrogates for clinical benefit and plan quality. Mean bowel QOL was assessed at 15 and 36 months posttreatment and the likelihood of 1× (5 points) or 2× (10 points) minimally important difference changes were assessed.

Results: Rectal V70 was correlated with physician scored toxicity (P = .033) and was used as a surrogate for plan quality. There was no correlation between prostate volume and rectal V70 (r = 0.077). Rectal V70 pre- and post-hydrogel was 13% and 3% for the smallest prostates (<40 mL) and 12% and 2% for the largest (>80 mL). The relative reduction in rectal V70 of 78% did not vary by prespacer V70, but the absolute reduction was greater for a higher V70. All spacer plans met the 5 QUANTEC rectal dose constraints, although 92% of control plans met all constraints. At 3 years, those not meeting all QUANTEC goals had a 15.0-point (standard deviation 15.1) decline, control patients meeting QUANTEC goals had a 4.0-point (9.5) decline, and spacer had >0.5 (7.6; P < .01). Previous surgery was not correlated with QOL (P = .8). Across prognostic groups, including age, body mass index, previous surgery, target volume, or quality of radiation plans, there was no statistically significant heterogeneity in the relative benefit of spacer in decreasing the risk of 1× or 2× the minimally important difference declines.

Conclusions: There was little heterogeneity in the likelihood of spacer reducing the risk of declines in bowel QOL across clinical and dosimetric variables. Even for the >95% of plans meeting QUANTEC rectal criteria, hydrogel spacer provided potentially meaningful benefits.
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http://dx.doi.org/10.1016/j.prro.2019.12.011DOI Listing
December 2020

Radiosurgery for Unruptured Intervention-Naïve Pediatric Brain Arteriovenous Malformations.

Neurosurgery 2020 08;87(2):368-376

Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia.

Background: Long-term data regarding stereotactic radiosurgery (SRS) as a standalone therapy for unruptured pediatric brain arteriovenous malformations (AVMs) are incompletely defined.

Objective: To evaluate, in a multicenter, retrospective cohort study, the outcomes after SRS for unruptured, intervention-naïve pediatric AVMs.

Methods: To retrospectively analyze the International Radiosurgery Research Foundation pediatric AVM database from 1987 to 2018. Pediatric patients with unruptured, previously untreated AVMs who underwent SRS were included. The primary endpoint was a composite of hemorrhagic stroke, death, or permanently symptomatic radiation-induced changes.

Results: The study cohort comprised 101 patients (mean follow-up 80.8 mo). The primary endpoint occurred in 14%, comprising hemorrhagic stroke, death, and permanent radiation-induced changes in 6%, 3%, and 8%, respectively. Estimated probabilities of the primary endpoint were 5.2%, 10.8%, and 23.0% at 2, 5, and 10 yr, respectively. Estimated probabilities of AVM obliteration at 5 and 10 yr were 64% and 82%, respectively. Single SRS treatment (P = .007) and higher margin dose (P = .005) were predictors of obliteration. Subgroup analysis of Spetzler-Martin grade I-III AVMs estimated primary endpoint probabilities of 3.7%, 8.4%, and 18.7% at 2, 5, and 10 yr, respectively.

Conclusion: Treatment of unruptured, intervention-naïve AVMs in the pediatric population with SRS carries an approximately 2% annual risk of morbidity and mortality, which appears to plateau after 10 yr. The poorly described natural history of pediatric AVMs renders any comparison of SRS vs conservative management imperfect.
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http://dx.doi.org/10.1093/neuros/nyz558DOI Listing
August 2020

Amelioration of Mucositis in Proton Therapy of Fanconi Anemia Fanca Mice by JP4-039.

In Vivo 2019 Nov-Dec;33(6):1757-1766

Department of Radiation Oncology, Beaumont Health, Royal Oak, MI, U.S.A.

Background/aim: We tested JP4-039, a GS-nitroxide radiation damage mitigator in proton therapy of Fanconi anemia (FA) mice.

Materials And Methods: Fanca and Fanca bone marrow stromal cells were pre-treated with JP4-039 and irradiated with either protons or photons (0-10 GyRBE) followed by clonogenic survival and β-Galactosidase senescence analysis. Fanca and Fanca mice were pretreated with JP4-039 for 10 min prior to oropharyngeal irradiation with either protons or photons (0 or 30 GyRBE) followed by sacrifice and measurement of oral cavity ulceration, distant hematopoietic suppression, and real-time polymerase chain reaction analysis.

Results: JP4-039 reduced oral cavity ulceration in Fanca mice, transcripts Nfkb, Ap1, Sp1, and Nrf2, and proton therapy induced distant marrow suppression.

Conclusion: JP4-039 protected Fanca and Fanca cells and mouse oral cavity from both proton and photon radiation.
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http://dx.doi.org/10.21873/invivo.11666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899135PMC
March 2020

Hypofractionation in Prostate Cancer Using Proton Beam.

Int J Radiat Oncol Biol Phys 2019 11;105(4):723-726

Beaumont Health, Department of Radiation Oncology, Royal Oak, Michigan. Electronic address:

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http://dx.doi.org/10.1016/j.ijrobp.2019.08.006DOI Listing
November 2019

Breast conserving therapy is associated with improved overall survival compared to mastectomy in early-stage, lymph node-negative breast cancer.

Radiother Oncol 2020 01 12;142:186-194. Epub 2019 Oct 12.

Department of Radiation Oncology, Beaumont Health, Royal Oak, United States. Electronic address:

Background And Purpose: Recent retrospective studies suggest improved overall survival (OS) with breast conserving therapy (BCT), including breast conserving surgery and adjuvant whole breast radiotherapy, compared to mastectomy in the modern era. The patient subset most likely to benefit from BCT remains unclear, and the role of Oncotype DX Recurrence Score (RS) in this context is unknown. We compared BCT to mastectomy in early-stage, node-negative breast cancer. We further explored outcomes after stratification by RS and age.

Materials And Methods: We performed a matched-cohort analysis of National Cancer Database (NCDB) patients with pT1-2, pN0, cM0 breast cancer treated between 2006 and 2014 with BCT or mastectomy. Patients were matched for all available baseline characteristics using propensity scores with inverse probability of treatment weighting (IPTW) with stabilized weights.

Results: We identified 144,263 eligible patients treated with BCT and 87,379 patients treated with mastectomy. After IPTW-matching, OS was higher with BCT compared to mastectomy: 5-year OS of 94.4% vs. 91.8% (P < 0.001) and 7-year OS of 90% vs. 85.2% (P < 0.001). Doubly robust multivariable analysis showed an association between BCT and improved OS (HR 0.66, 95% CI, 0.64-0.69, P < 0.001). In a subset analysis, BCT was associated with improved OS in patients with RS >25, but not patients with RS ≤25. When stratified by age, only patients >50 years had improved OS with BCT.

Conclusion: BCT is associated with improved OS compared to mastectomy in women with early-stage, node-negative breast cancer. The improvement in OS with BCT appears to be most pronounced in patients with high RS and >50 years of age. Prospective validation of these findings is required.
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http://dx.doi.org/10.1016/j.radonc.2019.09.018DOI Listing
January 2020

Trimodality therapy for atypical teratoid/rhabdoid tumor is associated with improved overall survival: A surveillance, epidemiology, and end results analysis.

Pediatr Blood Cancer 2019 12 28;66(12):e27969. Epub 2019 Aug 28.

Department of Radiation Oncology, Beaumont Health, Royal Oak, Michigan.

Background: Atypical teratoid/rhabdoid tumors (AT/RTs) are rare aggressive central nervous system tumors. The use of radiation therapy (RT) remains controversial, especially for patients younger than three years of age. The purpose of the current investigation is to robustly analyze the impact of RT among pediatric AT/RT patients using the Surveillance, Epidemiology, and End Results (SEER) database.

Methods: SEER 18 Custom Data registries were queried for AT/RT (ICD-0-3 9508/3). A total of 190 pediatric AT/RT patients were identified, of whom 102 underwent surgery + chemotherapy and 88 underwent trimodality therapy. Univariate and multivariable analyses using Kaplan-Meier and Cox proportional hazards regression modeling were performed. Propensity-score matched analysis with inverse probability of treatment weighting was performed to account for indication bias. The landmark method was used to account for immortal time bias.

Results: The majority of patients were <3 years old (75.8%). Patients <3 were more likely to be treated without RT as compared with older patients (62% vs 38%). Doubly robust MVA identified distant disease as a negative prognostic factor (HR 2.1, P = 0.003), whereas trimodality therapy was strongly protective (HR 0.39, P < 0.001). Infants (<1), toddlers (1-2), and older children (3+) all benefited from trimodality therapy, with largest benefit for infants (HR 0.34, P = 0.02) and toddlers (HR 0.31, P < 0.001).

Conclusion: The current study provides further evidence that trimodality therapy improves clinical outcomes among patients with AT/RT. This finding was most pronounced for younger patients; therefore, further studies are needed to confirm this finding in this vulnerable population.
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http://dx.doi.org/10.1002/pbc.27969DOI Listing
December 2019

Stereotactic Radiosurgery for Unruptured Versus Ruptured Pediatric Brain Arteriovenous Malformations.

Stroke 2019 10 7;50(10):2745-2751. Epub 2019 Aug 7.

From the Department of Neurological Surgery, University of Virginia Health System, Charlottesville (C.-J.C., K.N.K., N.I., J.P.S.).

Background and Purpose- The effects of prior hemorrhage on stereotactic radiosurgery (SRS) outcomes for pediatric arteriovenous malformations (AVMs) are not well defined. The aim of this multicenter, retrospective cohort study is to compare the SRS outcomes for unruptured versus ruptured pediatric AVMs. Methods- The International Radiosurgery Research Foundation pediatric AVM database from 1987 to 2018 was reviewed retrospectively. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes. Associations between prior hemorrhage and outcomes were adjusted for baseline differences, inverse probability weights, and competing risks. Results- The study cohort comprised 153 unruptured and 386 ruptured AVMs. Favorable outcome was achieved in 48.4% and 60.4% of unruptured and ruptured AVMs, respectively (adjusted odds ratio, 1.353; =0.190). Cumulative AVM obliteration probabilities were 51.2%, 59.4%, 64.2%, and 70.0% for unruptured and 61.0%, 69.3%, 74.0%, and 79.3% for ruptured AVMs at 4, 6, 8, and 10 years, respectively (subhazard ratio, 1.311; =0.020). Cumulative post-SRS hemorrhage probabilities were 4.5%, 5.6%, 5.6%, and 9.8% for unruptured and 4.7%, 6.1%, 6.1%, and 10.6% for ruptured AVMs at 4, 6, 8, and 10 years, respectively (subhazard ratio, 1.086; =0.825). Probabilities of AVM obliteration (adjusted subhazard ratio, 0.968; =0.850) and post-SRS hemorrhage (adjusted subhazard ratio, 1.663; =0.251) were comparable between the 2 cohorts after inverse probability weight adjustments. Symptomatic (15.8% versus 8.1%; adjusted odds ratio, 0.400; =0.008) and permanent (9.2% versus 5.0%; adjusted odds ratio, 0.441; =0.045) radiation-induced change were more common in unruptured AVMs. Conclusions- The overall outcomes after SRS for unruptured versus ruptured pediatric AVMs are comparable. However, symptomatic and permanent radiation-induced change occur more frequently in pediatric patients with unruptured AVMs.
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http://dx.doi.org/10.1161/STROKEAHA.119.026211DOI Listing
October 2019

Neoadjuvant radiation therapy for the management of myoepithelial carcinoma of the upper extremity.

Int J Cancer 2018 02 14;142(4):854-862. Epub 2017 Nov 14.

Department of Radiation Oncology, Albert-Einstein College of Medicine-Montefiore Medical Center, Bronx, NY.

Myoepithelial tumors of the soft tissue are a rare tumor displaying myoepithelial elements and lacking obvious ductal differentiation. The rarity of these precludes any evidence-based consensus regarding optimal management. Nevertheless, the current approach to these lesions begins with amputation or complete excision. The efficacy of neoadjuvant or adjuvant radiation therapy or chemotherapy has not been established. Here, we present the first report to the authors' knowledge of neoadjuvant radiation therapy for the treatment of this rare soft tissue neoplasm and review the management and outcomes of published cases of myoepithelial carcinoma. A patient with a soft tissue myoepithelial carcinoma that declined both amputation and chemotherapy was treated with neoadjuvant radiation therapy and wide surgical excision followed by a brachytherapy boost to the resected tumor bed. Neoadjuvant radiation therapy resulted in an excellent response with extensive treatment-related changes consisting predominantly of fibrosis, hyalinization and hemorrhage and only 10% residual viable myoepithelial carcinoma present in the surgical specimen.
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http://dx.doi.org/10.1002/ijc.31101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038801PMC
February 2018

The predictive value of SS-16 in clinically diagnosed Parkinson's disease patients: comparison with (99m)Tc-TRODAT-1 SPECT scans.

Transl Neurodegener 2016 20;5:15. Epub 2016 Aug 20.

Department of Neurology & Institute of Neurology, Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.

Background: Dopamine transporter based imaging has high diagnostic performance in distinguishing patients with Parkinson's disease (PD) from patients with non-Parkinsonian syndromes. Our previous study indicated that the "Sniffin' Sticks" odor identification test (SS-16) acts as a valid instrument for olfactory assessment in Chinese PD patients. The aim of the study was to compare the efficacy of the two methods in diagnosing PD.

Methods: Fifty-two PD patients were involved in this study and underwent single photon emission computed tomography (SPECT) imaging using the labeled dopamine transporter radiotracer (99m)Tc-TRODAT-1 to assess nigrostriatal dopaminergic function. Olfactory function was assessed with the "Sniffin' Sticks" odor identification test (SS-16) in all patients who received DAT-SPECT scanning. Statistical analysis (SPSS version 21) was carried out to determine the diagnostic accuracy of SS-16 as well as its correlation with (99m)Tc-TRODAT-1 SPECT, its positive predictive value (PPV), and negative predictive value (NPV).

Results: We identified a negative correlation between SS-16 and DAT SPECT (Kappa = 0.269, p = 0.004). By using the (99m)Tc-TRODAT-1 uptake results as the gold standard, the sensitivity and specificity of SS-16 was 56.8 and 37.5 %, respectively. Furthermore, the negative and positive predictive values were calculated as 13.6 and 83.3 %, respectively.

Conclusions: SS-16 would not be used as a diagnostic tool for early stage PD patients. Negative results of SS-16 would not exclude the diagnosis of PD. Further tests are needed for validation.
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http://dx.doi.org/10.1186/s40035-016-0062-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992567PMC
August 2016

Salivary total α-synuclein, oligomeric α-synuclein and SNCA variants in Parkinson's disease patients.

Sci Rep 2016 06 23;6:28143. Epub 2016 Jun 23.

Department of Neurology &Institute of Neurology, Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.

The present study was to evaluate the diagnostic value of salivary total and oligomeric α-synuclein levels in PD. Furthermore, we sought to explore the relationship between salivary total α-synuclein and α-synuclein SNP variants levels. 201 PD patients and 67 controls were recruited, of which there also had the genetic information of two positive α-synuclein (SNCA) loci. Salivary total α-synuclein was assayed using a highly sensitive Luminex assay and oligomeric α-synuclein was quantified by the combination of Gel filtration chromatography and Western blot, respectively. From our analysis,No difference in salivary total α-synuclein levels was found between PD patients and healthy controls, it decreased with age in PD patients, and was closely associated with genotypic distribution of rs11931074 and rs894278 in PD, respectively. After controlled for age and genders, G allele of rs11931074 was correlated with lower salivary total α-synuclein levels, while G allele of rs894278 was also correlated with the higher levels. Simultaneously, the further study was shown that salivary oligomeric α-synuclein in PD patients significantly increased comparing to healthy controls. In conclusions,our study firstly demonstrated that salivary total α-synuclein levels could be manipulated by different α-synuclein SNPs and salivary oligomeric α-synuclein could be a potential diagnostic indicator of PD.
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http://dx.doi.org/10.1038/srep28143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917865PMC
June 2016
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