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Intensity-modulated proton therapy (IMPT) interplay effect evaluation of asymmetric breathing with simultaneous uncertainty considerations in patients with non-small cell lung cancer

Shan, Jie; Yang, Yunze; Schild, Steven E; Daniels, Thomas B; Wong, William W; Fatyga, Mirek; Bues, Martin; Sio, Terence T; Liu, Wei
PURPOSE/OBJECTIVE:Intensity-modulated proton therapy (IMPT) is sensitive to uncertainties from patient setup and proton beam range, as well as interplay effect. In addition, respiratory motion may vary from cycle to cycle, and also from day to day. These uncertainties can severely degrade the original plan quality and potentially affect patient's outcome. In this work, we developed a new tool to comprehensively consider the impact of all these uncertainties and provide plan robustness evaluation under them. METHODS:We developed a comprehensive plan robustness evaluation tool that considered both uncertainties from patient setup and proton beam range, as well as respiratory motion simultaneously. To mimic patients' respiratory motion, the time spent in each phase was randomly sampled based on patient-specific breathing pattern parameters as acquired during the four-dimensional (4D)-computed tomography (CT) simulation. Spots were then assigned to one specific phase according to the temporal relationship between spot delivery sequence and patients' respiratory motion. Dose in each phase was calculated by summing contributions from all the spots delivered in that phase. The final 4D dynamic dose was obtained by deforming all doses in each phase to the maximum exhalation phase. Three hundred (300) scenarios (10 different breathing patterns with 30 different setup and range uncertainty scenario combinations) were calculated for each plan. The dose-volume histograms (DVHs) band method was used to assess plan robustness. Benchmarking the tool as an application's example, we compared plan robustness under both three-dimensional (3D) and 4D robustly optimized IMPT plans for 10 nonrandomly selected patients with non-small cell lung cancer. RESULTS:, P = 0.020) favoring 4D plans and comparable normal tissue sparing including esophagus, heart, and spinal cord for both 3D and 4D plans were observed. The calculation time for all patients included in this study was 11.4 ± 2.6 min. CONCLUSION/CONCLUSIONS:A comprehensive plan robustness evaluation tool was successfully developed and benchmarked for plan robustness evaluation in the presence of interplay effect, setup and range uncertainties. The very high efficiency of this tool marks its clinical adaptation, highly practical and versatile nature, including possible real-time intra-fractional interplay effect evaluation as a potential application for future use.
PMID: 32964474
ISSN: 2473-4209
CID: 4631192

Early Outcomes of Patients With Locally Advanced Non-small Cell Lung Cancer Treated With Intensity-Modulated Proton Therapy Versus Intensity-Modulated Radiation Therapy: The Mayo Clinic Experience

Yu, Nathan Y; DeWees, Todd A; Liu, Chenbin; Daniels, Thomas B; Ashman, Jonathan B; Beamer, Staci E; Jaroszewski, Dawn E; Ross, Helen J; Paripati, Harshita R; Rwigema, Jean-Claude M; Ding, Julia X; Shan, Jie; Liu, Wei; Schild, Steven E; Sio, Terence T
Purpose/UNASSIGNED:There are very little data available comparing outcomes of intensity-modulated proton therapy (IMPT) to intensity-modulated radiation therapy (IMRT) in patients with locally advanced NSCLC (LA-NSCLC). Methods/UNASSIGNED: = 46 [58%]) from 2016 to 2018 at our institution. Survival rates were calculated using the Kaplan-Meier method and compared with the log-rank test. Acute and subacute toxicities were graded based on Common Terminology Criteria for Adverse Events, version 4.03. Results/UNASSIGNED: = .47). There was 1 treatment-related death from radiation pneumonitis 6 months after IMRT in a patient with idiopathic pulmonary fibrosis. Conclusions/UNASSIGNED:Compared with IMRT, our early experience suggests that IMPT resulted in similar outcomes in a frailer population of LA-NSCLC who were more often being reirradiated. The role of IMPT remains to be defined prospectively.
PMID: 32529140
ISSN: 2452-1094
CID: 4631182

Expanding the Spectrum of Radiation Necrosis After Stereotactic Radiosurgery (SRS) for Intracranial Metastases From Lung Cancer: A Retrospective Review

Sharma, Akanksha; Mountjoy, Luke J; Butterfield, Richard J; Zhang, Nan; Ross, Helen J; Schild, Steven E; Sio, Terence T; Daniels, Thomas B; Paripati, Harshita R; Mrugala, Maciej M; Vora, Sujay A; Patel, Naresh P; Zimmerman, Richard S; Ashman, Jonathan B; Porter, Alyx B
OBJECTIVE:Radiation therapy (RT) is the primary treatment of intracranial metastasis (ICM) from lung cancer (LC). Radiation necrosis (RN) has been reported post-RT with an incidence of 5% to 24%. We reviewed the spectrum of imaging changes in patients treated with RT for ICM from LC in an effort to identify potential risk factors for RN. METHODS:We reviewed 63 patients with LC and ICM who received RT (radiosurgery [stereotactic radiosurgery] with/without whole brain radiation therapy) at our institution between 2013 and 2018. Data evaluated included demographics, tumor type, ICM burden and location, chemotherapy, surgery, and RT details as well as treatment choices and outcomes. RESULTS:Of the 63 patients, clinical and radiographic criteria for RN were noted in 24 (38%) as early as 2 months and as late as 5 years posttreatment. Six patients required surgical resection due to refractory symptoms revealing pathology-proven RN and occasionally tumor. Patients were significantly more likely to develop RN if they had surgical resection of an ICM (45.8% vs. 20.5%, P=0.05). No differences were found in location, size, or genetic profile of lesions. In total, 80% of patients received treatment for symptoms and/or radiographic change. This was generally a combination of steroids, bevacizumab, laser interstitial thermal treatment, or surgical resection. Most patients required >1 treatment modality. CONCLUSIONS:This review of outcomes of RT for ICM in LC demonstrates a higher rate of RN than previously reported in the literature in those having had a surgical resection plus stereotactic radiosurgery. Our observation of RN as late as 5 years post-RT for ICM necessitates clinician awareness.
PMID: 31764021
ISSN: 1537-453x
CID: 4631162

Clinical evaluation of fitness to drive in patients with brain metastases

Valencia-Sanchez, Cristina; Gorelkin, Vanessa C; Mrugala, Maciej M; Sharma, Akanksha; Vora, Sujay A; Ashman, Jonathan B; Daniels, Thomas B; Halyard, Michele Y; Rule, William G; Zhang, Nan; Butterfield, Richard J; Schild, Steven E; Porter, Alyx B
Background/UNASSIGNED:Guidelines to provide recommendations about driving restrictions for patients with brain metastases are lacking. We aim to determine whether clinical neurologic examination is sufficient to predict suitability to drive in these patients by comparison with an occupational therapy driving assessment (OTDA). Methods/UNASSIGNED:We prospectively evaluated the concordance between neurology assessment of suitability to drive (pass/fail) and OTDA in 41 individuals with brain metastases. Neuro-oncology evaluation included an interview and neurological examination. Participants subsequently underwent OTDA during which a battery of objective measures of visual, cognitive, and motor skills related to driving was administered. Results/UNASSIGNED:= .0046). The sensitivity of the neurology assessment to predict driving fitness compared with OTDA was 16.1% and the specificity 90%. The 31 patients who failed OTDA were more likely to fail Vision Coach, Montreal Cognitive Assessment, and Trail Making B tests. Conclusions/UNASSIGNED:There was poor association between the assessment of suitability to drive by neurologists and the outcome of the OTDA in patients with brain metastases. Subtle deficits that may impair the ability to drive safely may not be evident on neurologic examination. The positive predictive value was high to predict OTDA failure. Age could be a factor affecting OTDA performance. The results raise questions about the choice of assessments in making recommendations about driving fitness in people with brain metastases. OTDA should be strongly considered in patients with brain metastases who wish to continue driving.
PMID: 31832219
ISSN: 2054-2577
CID: 4631172

Technical Note: Treatment planning system (TPS) approximations matter - comparing intensity-modulated proton therapy (IMPT) plan quality and robustness between a commercial and an in-house developed TPS for nonsmall cell lung cancer (NSCLC)

Liu, Chenbin; Yu, Nathan Y; Shan, Jie; Bhangoo, Ronik S; Daniels, Thomas B; Chiang, Jennifer S; Ding, Xiaoning; Lara, Pedro; Patrick, Christopher L; Archuleta, James P; DeWees, Todd; Hu, Yanle; Schild, Steven E; Bues, Martin; Sio, Terence T; Liu, Wei
PURPOSE/OBJECTIVE:Approximate dose calculation methods were used in the nominal dose distribution and the perturbed dose distributions due to uncertainties in a commercial treatment planning system (CTPS) for robust optimization in intensity-modulated proton therapy (IMPT). We aimed to investigate whether the approximations influence plan quality, robustness, and interplay effect of the resulting IMPT plans for the treatment of locally advanced lung cancer patients. MATERIALS AND METHODS/METHODS:(Varian Medical Systems, Palo Alto, CA, USA), respectively. The plans were designed to deliver prescription doses to internal target volumes (ITV) drawn by a physician on averaged four-dimensional computed tomography (4D-CT). Solo plans were imported back to CTPS, and recalculated in CTPS for fair comparison. Both plans were further verified for each patient by recalculating doses in the inhalation and exhalation phases to ensure that all plans met clinical requirements. Plan robustness was quantified on all phases using dose-volume-histograms (DVH) indices in the worst-case scenario. The interplay effect was evaluated for every plan using an in-house developed software, which randomized starting phases of each field per fraction and accumulated dose in the exhalation phase based on the patient's breathing motion pattern and the proton spot delivery in a time-dependent fashion. DVH indices were compared using Wilcoxon rank-sum test. RESULTS:: 18.87 vs 22.29 Gy(RBE), P = 0.014]. CONCLUSIONS:Solo-generated IMPT plans provide improved cord sparing, better target robustness in all considered phases, and reduced interplay effect compared with CTPS. Consequently, the approximation methods currently used in commercial TPS programs may have space for improvement in generating optimal IMPT plans for patient cases with locally advanced lung cancer.
PMID: 31498885
ISSN: 2473-4209
CID: 4631152

The Search for Optimal Stereotactic Body Radiotherapy Dose in Inoperable, Centrally Located Non-Small-Cell Lung Cancer Continues [Comment]

Sio, Terence T; Mohindra, Pranshu; Yu, Nathan Y; Ashman, Jonathan B; Daniels, Thomas B; Merrell, Kenneth W; Schild, Steven E
PMID: 31465261
ISSN: 1527-7755
CID: 4631142

Small-cell Lung Cancer in Very Elderly (≥ 80 Years) Patients

Schild, Steven E; Zhao, Liming; Wampfler, Jason A; Daniels, Thomas B; Sio, Terence; Ross, Helen J; Paripati, Harshita; Marks, Randolph S; Yi, Joanne; Liu, Han; He, Yanqi; Yang, Ping
BACKGROUND:This analysis was performed to describe the outcome of very elderly (≥ 80 years) patients with small-cell lung cancer (SCLC) as there is no published data regarding these patients. MATERIALS AND METHODS:One hundred forty-six very elderly patients with SCLC were identified from the Institutional Lung Cancer Database ranging in age from 80 to 92 years (median, 82 years). Of these, 47 (32%) patients had limited-stage SCLC (L-SCLC), and 99 (68%) had extensive-stage SCLC (E-SCLC). All were Caucasian, and the majority (64%) were female. Sixty-seven (46%) patients had Zubrod performance status (PS) of 0 to 1. RESULTS:Of the 146 patients, 44 (30%) received no therapy, 65 (45%) received chemotherapy alone, 27 (19%) received chemotherapy plus local therapy (thoracic radiotherapy [TRT] or surgery), and 10 (7%) received local therapy alone. The median survival was 5.4 months. On univariable analysis, age (P = .019), stage (L-SCLC vs. E-SCLC; P = .0002), PS (P < .0001), and treatment option (P < .0001) were associated with survival. On multivariable analysis, stage (P = .011), PS (P = .029), and treatment option (P < .0001) maintained significance. For entire cohort, the median survival was 1.3 months without active therapy, 6 months with local therapy alone, 7.2 months with chemotherapy alone, and 14.4 months with chemotherapy plus local therapy (P < .0001, univariable and multivariable). Similar survival findings in response to treatment were found when the L-SCLC and E-SCLC cohorts were separately analyzed. CONCLUSIONS:The survival of very elderly patients with SCLC was associated with stage (L-SCLC vs. E-SCLC), PS, and treatment option. Very elderly patients with SCLC often have limited functional reserve required to tolerate aggressive multimodality therapy but appeared to benefit from it. Geriatric assessments, careful monitoring, and extra support are warranted in elderly patients. Care should be individualized based on the desires and needs of each patient.
PMID: 31155475
ISSN: 1938-0690
CID: 4631132

Radiation and the heart: systematic review of dosimetry and cardiac endpoints

Niska, Joshua R; Thorpe, Cameron S; Allen, Sorcha M; Daniels, Thomas B; Rule, William G; Schild, Steven E; Vargas, Carlos E; Mookadam, Farouk
INTRODUCTION/BACKGROUND:Recent trials in radiotherapy have associated heart dose and survival, inadequately explained by the existing literature for radiation-related late cardiac effects.  Authors aimed to review the recent literature on cardiac dosimetry and survival/cardiac endpoints. Areas covered: Systematic review of the literature in the past 10 years (2008-2017) was performed to identify manuscripts reporting both cardiac dosimetry and survival/cardiac endpoints.  Authors identified 64 manuscripts for inclusion, covering pediatrics, breast cancer, lung cancer, gastrointestinal diseases (primarily esophageal cancer), and adult lymphoma. Expert commentary: In the first years after radiotherapy, high doses (>40 Gy) to small volumes of the heart are associated with decreased survival from an unknown cause.  In the long-term, mean heart dose is associated with a small increased absolute risk of cardiac death.  For coronary disease, relative risk increases roughly 10% per Gy mean heart dose, augmented by age and cardiac risk factors.  For valvular disease and heart failure, doses >15 Gy substantially increase risk, augmented by anthracyclines.  Arrhythmias after radiotherapy are poorly described but may account for the association between upper heart dose and survival.  Symptomatic pericardial effusion typically occurs with doses >40 Gy.  Close follow-up and mitigation of cardiovascular risk factors are necessary after thoracic radiotherapy.
PMID: 30360659
ISSN: 1744-8344
CID: 4631122

Small-spot intensity-modulated proton therapy and volumetric-modulated arc therapies for patients with locally advanced non-small-cell lung cancer: A dosimetric comparative study

Liu, Chenbin; Sio, Terence T; Deng, Wei; Shan, Jie; Daniels, Thomas B; Rule, William G; Lara, Pedro R; Korte, Shawn M; Shen, Jiajian; Ding, Xiaoning; Schild, Steven E; Bues, Martin; Liu, Wei
PURPOSE/OBJECTIVE:To compare dosimetric performance of volumetric-modulated arc therapy (VMAT) and small-spot intensity-modulated proton therapy for stage III non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS/METHODS:A total of 24 NSCLC patients were retrospectively reviewed; 12 patients received intensity-modulated proton therapy (IMPT) and the remaining 12 received VMAT. Both plans were generated by delivering prescription doses to clinical target volumes (CTV) on averaged 4D-CTs. The dose-volume-histograms (DVH) band method was used to quantify plan robustness. Software was developed to evaluate interplay effects with randomized starting phases of each field per fraction. DVH indices were compared using Wilcoxon rank sum test. RESULTS:. Other DVH indices were comparable. The IMPT plans still met the standard clinical requirements with interplay effects considered. CONCLUSIONS:Small-spot IMPT improves cord, heart, and lung sparing compared to VMAT and achieves clinically acceptable plan robustness at least for the patients included in this study with motion amplitude less than 11 mm. Our study supports the usage of IMPT to treat some lung cancer patients.
PMID: 30328674
ISSN: 1526-9914
CID: 4631112

Fatal Radiation Pneumonitis in Patients With Subclinical Interstitial Lung Disease [Case Report]

Niska, Joshua R; Schild, Steven E; Rule, William G; Daniels, Thomas B; Jett, James R
PMID: 29526532
ISSN: 1938-0690
CID: 4631092