Simultaneous MV-kV imaging for intrafractional motion management during volumetric-modulated arc therapy delivery.

The purpose of this study was to evaluate the accuracy and clinical feasibility of a motion monitoring method employing simultaneously acquired MV and kV images during volumetric-modulated arc therapy (VMAT). Short-arc digital tomosynthesis (SA-DTS) is used to improve the quality of the MV images that are then combined with orthogonally acquired kV images to assess 3D motion. An anthropomorphic phantom with implanted gold seeds was used to assess accuracy of the method under static, typical prostatic, and respiratory motion scenarios. Automatic registra-tion of kV images and single MV frames or MV SA-DTS reconstructed with arc lengths from 2° to 7° with the appropriate reference fiducial template images was performed using special purpose-built software. Clinical feasibility was evaluated by retrospectively analyzing images acquired over four or five sessions for each of three patients undergoing hypofractionated prostate radiotherapy. The standard deviation of the registration error in phantom using MV SA-DTS was similar to single MV images for the static and prostate motion scenarios (σ = 0.25 mm). Under respiratory motion conditions, the standard deviation of the registration error increased to 0.7mm and 1.7 mm for single MV and MV SA-DTS, respectively. Registration failures were observed with the respiratory scenario only and were due to motion-induced fiducial blurring. For the three patients studied, the mean and standard deviation of the difference between automatic registration using 4° MV SA-DTS and manual registration using single MV images results was 0.07±0.52mm. The MV SA-DTS results in patients were, on average, superior to single-frame MV by nearly 1 mm - significantly more than what was observed in phantom. The best MV SA-DTS results were observed with arc lengths of 3° to 4°. Registration failures in patients using MV SA-DTS were primarily due to blockage of the gold seeds by the MLC. The failure rate varied from 2% to 16%. Combined MV SA-DTS and kV imaging is feasible for intratreatment motion monitoring during VMAT of anatomic sites where limited motion is expected, and improves registration accuracy compared to single MV/kV frames. To create a clinically robust technique, further improvements to ensure visualization of fiducials at the desired control points without degradation of the treatment plan are needed.

The Secondary Pulmonary Hypertension Diagnosis is Not Useful in Lung Allocation.

BACKGROUND: In lung transplant, the United Network for Organ Sharing (UNOS) contains a diagnosis of secondary pulmonary hypertension (SPH). SPH and pulmonary arterial hypertension are treated the same in the allocation scoring system. It is not clear whether utilizing the SPH diagnosis instead of the primary diagnosis is helpful to patients or providers. METHODS: Analysis of UNOS data from May 2005 through July 2021, comparing patients listed under the SPH diagnosis with patients listed under COPD and interstitial lung disease (ILD) who met criteria for PH (COPD-PH and ILD-PH, respectively), as well as patients listed under pulmonary arterial hypertension (primary pulmonary hypertension, PPH). Competing-risk analysis examined waitlist and post-transplant outcomes. An exploratory analysis of UNOS spirometry data was performed. RESULTS: Compared to patients listed under the SPH diagnosis, patients with ILD-PH were more likely to undergo transplantation (adjusted HR: 1.34, 95% confidence interval: 1.16-1.54, P < .001), with no significant difference comparing the SPH diagnosis to PPH or to COPD-PH. Waitlist mortality did not vary between groups. Post-transplant survival was lower in patients with PPH (adjusted HR: 1.35, 95% confidence interval: 1.04-1.75, P = .025), with no significant difference comparing the SPH diagnosis to COPD-PH or ILD-PH. Spirometry failed to demonstrate a clear phenotype within the SPH diagnosis. CONCLUSION: In an adjusted analysis, patients with advanced lung disease and secondary PH were more likely to undergo transplantation when listed for ILD than when listed under the SPH diagnosis. The SPH diagnosis is too clinically heterogeneous to be useful in predictive models and should be considered for removal from UNOS.

Feasibility of a Novel Real-Time Provider Teaching Intervention in Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Background: It is not known whether an intervention using real-time provider teaching in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) improves provider knowledge and/or patient outcomes. Objective: To pilot the combination of a novel, real-time provider teaching intervention delivered by subspecialists to Internal Medicine trainees with a traditional patient education and medication reconciliation (PEMR) intervention and to assess the impact of these interventions on provider knowledge regarding COPD and patient care. Methods: This was a single-center, nonrandomized, quality-improvement study. Patients admitted with AECOPD were prospectively identified between June 19 and November 20, 2019. Patients with asthma, lung cancer, or interstitial lung disease were excluded. The primary care team received a novel intervention featuring in-person, real-time teaching, covering Global Initiative on Chronic Obstructive Lung Disease COPD groups and management, including pulmonary rehabilitation referral. Providers completed a knowledge assessment before and after their real-time teaching session. Provider knowledge scores before and after teaching were compared using McNemar's test. Patients received a traditional PEMR intervention from a nurse practitioner and/or clinical pharmacist. A retrospective chart review was conducted for 50 historical control patients admitted with AECOPD to obtain preintervention rates of discharge on long-acting bronchodilators and referral to pulmonary rehabilitation. The proportions of patients discharged on long-acting bronchodilators and referred to pulmonary rehabilitation in the intervention group were compared with the preintervention historical control patients using chi-square testing. Results: Seventy-one providers caring for patients with AECOPD received real-time teaching. Postintervention, there was significant improvement in knowledge scores pertaining to Global Initiative on Chronic Obstructive Lung Disease groups and exacerbation risk (81% correct vs. 43% on pretest; P < 0.001) and guideline-directed treatment (83% correct vs. 28% on pretest; P < 0.001). Out of 44 eligible patients, 75% (n = 33 patients) received the PEMR intervention. Ninety percent of patients (n = 40 patients) were discharged on any long-acting inhaler, similar to the group of preintervention control subjects. Pulmonary rehabilitation referrals were made for 50% of patients (n = 22 patients) compared with 6% of preintervention control subjects (n = 3 patients; P < 0.001). Conclusion: In this single-center quality-improvement study, the combination of a novel, real-time provider teaching intervention and a traditional PEMR intervention improved provider knowledge and was associated with increased referrals to pulmonary rehabilitation.

Genomic Analyses for Predictors of Response to Chemoradiation in Stage III Non-Small Cell Lung Cancer.

BACKGROUND: Radiation with platinum-based chemotherapy is the standard of care for unresectable stage III non-small cell lung cancer (NSCLC). Despite aggressive treatment, progression-free survival and overall survival remain poor. It is unclear whether any tumor genetic mutations are associated with response to chemoradiation therapy. METHODS: We retrospectively reviewed clinical outcomes of patients with stage III NSCLC treated with definitive radiation who had undergone tumor molecular profiling through a next-generation DNA sequencing platform. Cox proportional hazards model was used to investigate associations between clinical outcomes and genetic mutations detected by next-generation sequencing. RESULTS: 110 patients were identified with stage III NSCLC and underwent definitive radiation between 2013 and 2017 and tumor molecular profiling. Concurrent or sequential chemotherapy was given in 104 patients (95%). Unbiased genomic analyses revealed a significant association between AKT2 mutations and decreased local-regional tumor control and overall survival (hazard ratios [HR] 12.5 and 13.7, P = .003 and P = .003, respectively). Analyses restricted to loss-of-function mutations identified KMT2C and KMT2D deleterious mutations as negative prognostic factors for overall survival (HR 13.4 and 7.0, P < .001 and P < .001, respectively). Deleterious mutations in a panel of 38 DNA damage response and repair pathway genes were associated with improved local-regional control (HR 0.32, P = .049). CONCLUSIONS: This study coupled multiplexed targeted sequencing with clinical outcome and identified mutations in AKT2, KMT2C, and KMT2D as negative predictors of local-regional control and survival, and deleterious mutations in damage response and repair pathway genes were associated with improved local-regional disease control after chemoradiation therapy. These findings will require validation in a larger cohort of patients with prospectively collected and detailed clinical information.

A Man in His 20s With Cough, Unilateral Pleural Effusion, and Nodular Pleural Thickening.

CASE PRESENTATION: A man in his 20s presented to the ED after several months of progressive dyspnea, dry cough, and night sweats. He had no chest pain, fevers, weight loss, or sick contacts. He was previously healthy and took no medications. Social history was notable for 5 pack-years of tobacco use. The patient was sexually active with male partners and had a recent partner infected with human T-lymphotropic virus. The patient worked in set design and window installations, and wore a respirator when working around solvents and resins. From ages 2 to 7 years, he frequently visited buildings at his parents' workplace that were undergoing asbestos abatement. From ages 7 to 24 years, he frequently visited pottery studios where talc-containing products were used. He frequently visited northern Massachusetts, and infections with Borrelia burgdorferi and Bartonella henselae were common in family members. His stepfather had recently been infected with Anaplasma. There was no family history of cancer.

Identifying the Optimal Radiation Dose in Locally Advanced Non-Small-cell Lung Cancer Treated With Definitive Radiotherapy Without Concurrent Chemotherapy.

INTRODUCTION: The optimal radiation dose for locally advanced non-small-cell lung cancer (NSCLC) is not known for patients who receive sequential chemoradiation (CRT) or definitive radiotherapy (RT) only. Our objective was to determine whether a benefit exists for radiation dose escalation for these patients. MATERIALS AND METHODS: The patients included in our retrospective analysis had undergone RT for NSCLC from 2004 to 2013, had not undergone surgery, and received a dose ≥ 50.0 Gy. Patients who received concurrent CRT were excluded from the analysis, leaving 336 patients for analysis. The primary outcomes were overall survival (OS), local failure (LF), and distant failure (DF). RESULTS: On multivariate analysis, after adjusting for age, Karnofsky performance status, gross tumor volume, and treatment modality, patients treated with a radiation dose > 66 Gy had significantly improved OS compared with those treated with < 60 Gy (hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.39-0.87; P = .008). After adjusting for smoking history and radiologic tumor size, patients treated with a radiation dose > 66 Gy had a significantly decreased risk of LF compared with those treated with < 60 Gy (HR, 0.59; 95% CI, 0.38-0.91; P = .02). The radiation dose was not an independent prognostic factor of DF on multivariate analysis. CONCLUSION: When controlling for tumor volume and/or dimensions and other independent prognostic factors, patients with locally advanced NSCLC who were not candidates for concurrent CRT benefited from a radiation dose > 66 Gy versus < 60 Gy with improved OS and reduced LF. An increased radiation dose did not appear to affect the incidence of DF.