Frequency of weight and body composition increases in advanced non-small cell lung cancer patients during first line therapy.

BACKGROUND: The primary objective of this study was to assess the frequency of body composition increases and their relationships to changes in body weight in two cohorts of real world, treatment-naïve, advanced non-small cell lung cancer (NSCLC) patients. One cohort received the current standard of care (CSOC), which consisted of immunotherapy and newer chemotherapy regimens, and the other cohort was treated with the former standard of care (FSOC), consisting only of older platinum-containing regimens. METHODS: CSOC (n = 106) and FSOC (n = 88) cohorts of advanced NSCLC patients were included in this study. Weights were collected at each clinical visit, and body composition analysis from routine chest computed tomography via automated segmentation software assessed at baseline and at 6 and 12 weeks. Standard statistical methods were used to calculate relationships between changes in weight and in body composition. RESULTS: The CSOC cohort contained 106 stage IV NSCLC patients treated between 16/12/2014 and 22/10/2020 while the FSOC cohort contained 88 stage III/IV NSCLC patients treated between 16/6/2006 and 18/11/2014. While each cohort exhibited decreases in median weight, body mass index (BMI), mean skeletal muscle index (SMI) and subcutaneous adipose tissue index (SATI) at the 6 and 12 week time points, a subset of patients experienced increases in these parameters. Using a threshold of ≥2.5% increase for weight, BMI, SMI, and SATI at the 12 week time point, both cohorts showed similar (20.5% and 27.3%) increases in these parameters. With a cut point of ≥5% increase at 12 weeks follow-up, 8.0% to 25.0% of the patients gained ≥5% in weight, BMI, SMI and SATI. Comparing these results in each cohort showed no significant differences. Pearson coefficients for weight change related to changes in SMI and SATI at 6 and 12 weeks ranged from 0.31 to 0.58 with all P values <0.02. Pearson coefficients for weight change at 12 weeks related to changes in VATI and IMATI ranged from 0.26 to 0.47 with all P values <0.05. Comparison of Pearson coefficients for each cohort showed no significant differences. CONCLUSIONS: Although decreases in median weight, BMI, SMI and SATI were observed in both cohorts, similar percentage of patients in each cohort experienced increases in these parameters. These findings, plus the positive correlations between longitudinal measurements of weight, muscle mass and adipose tissue, indicate that weight gain in these patients involves increases in both muscle mass and adipose tissue. Upon validation, these findings could have implications for clinical trial design and for translational research in cancer cachexia.

Examination of Firefighting as an Occupational Exposure Criteria for Lung Cancer Screening.

PURPOSE: Firefighting is known to be carcinogenic to humans. However, current lung cancer screening guidelines do not account for occupational exposure. We hypothesize that firefighting is an independent risk factor associated with the development of high-risk lung nodules on low-dose CT (LDCT). METHODS: Members of a firefighter's union underwent LDCT at a single institution between April 2022 and June 2023 within a lung cancer screening program. Results were interpreted by designated chest radiologists and reported using the Lung-RADS scoring system. Demographic and radiographic data were recorded, and summary statistics are reported. RESULTS: 1347 individuals underwent lung cancer screening, with a median age of 51 years (IQR 42-58), including 56 (4.2%) females. Overall, 899 (66.7%) were never smokers, 345 (25.6%) were former smokers, and 103 (7.7%) were current smokers. There were 41 firefighters (3.0%) who had high-risk (Lung-RADS 3 or 4) nodules requiring intervention or surveillance, of which 21 (1.5%) were Lung-RADS 3 and 20 (1.5%) that were Lung-RADS 4. Of the firefighters with high-risk nodules, only 6 (14.6%) were eligible for LDCT based on current screening guidelines. There were 7 high-risk nodules (0.5%) that required procedural intervention, 6 (85.7%) of which were from the non-screening eligible cohort. There were also 20 never-smoking firefighters (57.1%) with high-risk nodules that were non-screening eligible. CONCLUSION: Firefighting, even in the absence of smoking history, may be associated with the development of high-risk lung nodules on LDCT. Carefully selected occupational exposures should be considered in the development of future lung cancer screening guidelines.

A Case Report of Type B Aortic Dissection With Ruptured False Lumen.

Aortic dissection is a critical condition characterized by an intimal tear in the aortic wall, leading to the formation of a false lumen. We present a case of a 54-year-old male with chronic type B aortic dissection and hypertension who presented with acute tearing left back pain. Initial evaluation revealed elevated blood pressure and subtle laboratory abnormalities. Imaging confirmed a Stanford type B aortic dissection with an intramural hematoma and contained rupture of the false lumen. Despite initial stabilization efforts, the patient deteriorated rapidly and succumbed. This case highlights the critical importance of early diagnosis.

Development of a Novel Circulating Autoantibody Biomarker Panel for the Identification of Patients with 'Actionable' Pulmonary Nodules.

Due to poor compliance and uptake of LDCT screening among high-risk populations, lung cancer is often diagnosed in advanced stages where treatment is rarely curative. Based upon the American College of Radiology's Lung Imaging and Reporting Data System (Lung-RADS) 80-90% of patients screened will have clinically "non-actionable" nodules (Lung-RADS 1 or 2), and those harboring larger, clinically "actionable" nodules (Lung-RADS 3 or 4) have a significantly greater risk of lung cancer. The development of a companion diagnostic method capable of identifying patients likely to have a clinically actionable nodule identified during LDCT is anticipated to improve accessibility and uptake of the paradigm and improve early detection rates. Using protein microarrays, we identified 501 circulating targets with differential immunoreactivities against cohorts characterized as possessing either actionable (n = 42) or non-actionable (n = 20) solid pulmonary nodules, per Lung-RADS guidelines. Quantitative assays were assembled on the Luminex platform for the 26 most promising targets. These assays were used to measure serum autoantibody levels in 841 patients, consisting of benign (BN; n = 101), early-stage non-small cell lung cancer (NSCLC; n = 245), other early-stage malignancies within the lung (n = 29), and individuals meeting United States Preventative Screening Task Force (USPSTF) screening inclusion criteria with both actionable (n = 87) and non-actionable radiologic findings (n = 379). These 841 patients were randomly split into three cohorts: Training, Validation 1, and Validation 2. Of the 26 candidate biomarkers tested, 17 differentiated patients with actionable nodules from those with non-actionable nodules. A random forest model consisting of six autoantibody (Annexin 2, DCD, MID1IP1, PNMA1, TAF10, ZNF696) biomarkers was developed to optimize our classification performance; it possessed a positive predictive value (PPV) of 61.4%/61.0% and negative predictive value (NPV) of 95.7%/83.9% against Validation cohorts 1 and 2, respectively. This panel may improve patient selection methods for lung cancer screening, serving to greatly reduce the futile screening rate while also improving accessibility to the paradigm for underserved populations.

Respiratory Musculature Evaluated by Computed Tomography in the Setting of Prolonged Mechanical Ventilation.

BACKGROUND: Diaphragm atrophy has been observed in subjects who undergo invasive mechanical ventilation. We propose a new method to assess for respiratory muscle (RM) changes in subjects who undergo invasive mechanical ventilation by assessing for changes in respiratory muscles through computed tomography (CT). METHODS: A retrospective case series study was conducted on subjects who underwent invasive mechanical ventilation and received at least 2 chest CT scans during admission. Exclusion criteria included history of chronic mechanical ventilation dependence and neuromuscular disease. Respiratory muscle cross-sectional area (CSA) was measured at the T6 vertebrae. RESULTS: Fourteen subjects were included: mean (± SD) age, BMI, and admission APACHE II scores were 54.0 y (± 14.9), 32.6 kg/m2 (± 10.9), and 23.5 (± 6.0), respectively. Ten (71%) subjects were male. Mean length of time between CT chest scans was 7.5 d (± 3.3). Mean duration of invasive mechanical ventilation was 4.5 d (± 3.4). The percentage change in TM CSA among those who underwent invasive mechanical ventilation was 10.5% (± 6.1). CONCLUSIONS: We demonstrated that serial analysis of respiratory muscle CSA through CT chest scans can be a method to assess for respiratory muscle atrophy in subjects undergoing mechanical ventilation. Future prospective studies involving larger populations are needed to better understand how this method can be used to predict outcomes in mechanically ventilated patients.

The association between thoracic sarcopenia and survival is gender specific in early-stage lung cancer.

Background: Sarcopenia, as measured at the 3rd lumbar (L3) level, has been shown to prognosticate survival in cancer patients. However, many patients with early-stage non-small cell lung cancer (NSCLC) do not undergo abdominal imaging. We hypothesized that preoperative thoracic sarcopenia is associated with survival in patients undergoing lung resection for early-stage NSCLC. Methods: Patients who underwent anatomic resection for NSCLC between 2010-2019 were retrospectively identified. Exclusion criteria included induction therapy, less than 90 days of follow-up, and absence of computed tomography (CT) imaging. Cross sectional skeletal muscle area was calculated at the fifth thoracic vertebra (T5), twelfth thoracic vertebra (T12), and L3 level. Gender-specific lowest quartile values and previously defined values were used to define sarcopenia. Overall survival and disease-free survival were assessed using the Kaplan-Meier method. Results: Overall, 221 patients met inclusion criteria with a median body mass index (BMI) of 26.5 kg/m2 [interquartile range (IQR), 23.3-29.9 kg/m2], age of 69 years (IQR, 62.4-74.9 years), and follow-up of 46.9 months (IQR, 25.0-70.7 months). At the T5 level, sarcopenic males demonstrated worse overall survival [median 41.0 (IQR, 13.8-53.7) vs. 42.0 (IQR, 23.1-55.1) months, P=0.023] and disease-free survival [median 15.8 (IQR, 8.4-30.78) vs. 34.8 (IQR, 20.1-50.5) months, P=0.007] when compared to non-sarcopenic males. There was no difference in survival between sarcopenic and non-sarcopenic females when assessed at T5. Sarcopenia at T12 or L3 was associated with worse overall survival (P<0.05). Conclusions: Sarcopenia at T5 is associated with worse survival in males, but not females. When using upper thoracic vertebral levels to assess for sarcopenia, it is necessary to account for gender.

Validation of skeletal muscle and adipose tissue measurements using a fully automated body composition analysis neural network versus a semi-automatic reference program with human correction in patients with lung cancer.

Rationale and objectives: To validate skeletal muscle and adipose tissues cross sectional area (CSA) and densities between a fully automated neural network (test program) and a semi-automated program requiring human correction (reference program) for lumbar 1 (L1) and lumbar 2 (L2) CT scans in patients with lung cancer. Materials and methods: Agreement between the reference and test programs was measured using Dice-similarity coefficient (DSC) and Bland-Altman plots with limits of agreement within 1.96 standard deviation. Results: A total of 49 L1 and 47 L2 images were analyzed from patients with lung cancer (mean age = 70.51 ± 9.48 years; mean BMI = 27.45 ± 6.06 kg/m2; 71% female, 55% self-identified as Black and 96% as non-Hispanic ethnicity). The DSC indicates excellent overlap (>0.944) or agreement between the two measurement methods for muscle, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) CSA and all tissue densities at L1 and L2. The DSC was lowest for intermuscular adipose tissue (IMAT) CSA at L1 (0.889) and L2 (0.919). Conclusion: The use of a fully automated neural network to analyze body composition at L1 and L2 in patients with lung cancer is valid for measuring skeletal muscle and adipose tissue CSA and densities when compared to a reference program. Further validation in a more diverse sample and in different disease and health states is warranted to increase the generalizability of the test program at L1 and L2.

Novel application of respiratory muscle index obtained from chest computed tomography to predict postoperative respiratory failure after major non-cardiothoracic surgery.

BACKGROUND: Postoperative respiratory failure (PRF) is a serious complication associated with significant morbidity and mortality. We propose a new method to predict PRF by utilizing computed tomography (CT) of the chest to assess degree of respiratory muscle wasting prior to surgery. METHODS: Patients who received a chest CT and required invasive mechanical ventilation (MV) after major non-cardiothoracic surgery were included. Exclusion criteria included cardiothoracic surgery. Respiratory muscle index (RMI) was calculated at the T6 vertebra measured on Slice-O-Matic® software. RESULTS: Thirty three patients met inclusion with a mean (±SD) age, BMI, and APACHE II score of 62.2 years (±12.1), 28.1 kg/m2 (±7.8), and 14.1 (±4.7). Most patients were female (n = 22 [67%]). Eleven patients (33%) developed PRF with a mean of 6.0 (±10.7) initial ventilation days. There was no difference in baseline demographics between groups. RMI values for the PRF group were significantly lower when compared to the non-PRF group: 22.7 cm2/m2 (±5.3) vs. 28.5 cm2/m2 (±5.9) (p = 0.008). CONCLUSION: Presence of respiratory muscle wasting prior to surgery was found to be associated with postoperative respiratory failure.

Case 287: Intrathoracic Migration of a Breast Implant after Video-assisted Thoracoscopic Surgery for Right Upper Lobectomy.

History A 60-year-old woman was diagnosed with a new right upper lobe stage I lung adenocarcinoma and underwent video-assisted thoracoscopic surgery (VATS) for right upper lobectomy. Her postoperative course was complicated by a large pneumothorax after chest tube removal on postoperative day 3. This was managed with repeat right-sided chest tube placement on the same day. The second chest tube was removed on postoperative day 8 without complications. A 2-week postoperative clinic visit was unremarkable. Postoperative chest radiographs on postoperative days 1, 3, and 8 are provided. Subsequently, chest CT scanning was performed as part of routine 6-month postsurgical lung cancer surveillance follow-up. The patient had no clinical complaints at routine follow-up. Physical examination revealed well-healed VATS scars in the chest wall. Laboratory results were within normal limits, including a normal white blood cell count of 6400/mL. Her surgical history included prior left upper lobectomy for remote left upper lobe stage IIIA adenocarcinoma and prior bilateral breast implantation for cosmesis. On the basis of chest CT findings, the patient was transferred from an outside institution.

Imaging Adult ECMO.

Adult extracorporal membrane oxygenation utilization in the ICU has rapidly increased. Newer technology and cannulation strategies and the complex hemodynamics make imaging interpretation challenging. There is also a high rate of complications. This review details the common indications, cannulation strategies, relevant hemodynamics and complications which impact imaging interpretation. Recommendations for modifying computed tomography protocols and techniques to obtain diagnostic images and some of the imaging pitfalls are also discussed.

Case 287.

History A 60-year-old woman was diagnosed with a new right upper lobe stage I lung adenocarcinoma and underwent video-assisted thoracoscopic surgery (VATS) for right upper lobectomy. Her postoperative course was complicated by a large pneumothorax after chest tube removal on postoperative day 3. This was managed with repeat right-sided chest tube placement on the same day. The second chest tube was removed on postoperative day 8 without complications. A 2-week postoperative clinic visit was unremarkable. Postoperative chest radiographs on postoperative days 1, 3, and 8 (Fig 1a-1c) are provided. Subsequently, chest CT scanning was performed as part of routine 6-month postsurgical lung cancer surveillance follow-up (Figs 2, 3). The patient had no clinical complaints at routine follow-up. Physical examination revealed well-healed VATS scars in the chest wall. Laboratory results were within normal limits, including a normal white blood cell count of 6400/µL. Her surgical history included prior left upper lobectomy for remote left upper lobe stage IIIA adenocarcinoma and prior bilateral breast implantation for cosmesis. On the basis of chest CT findings, the patient was transferred from an outside institution.

A 59-Year-Old Man With Chronic Kidney Disease After Kidney Transplantation Presents With Chronic Dyspnea.

CASE PRESENTATION: A 59-year-old man presented to the ED with a chief complaint of shortness of breath. His past medical history was significant for end-stage renal disease secondary to lithium toxicity, immunosuppression subsequent to cadaveric renal transplantation, bipolar disorder, and hypertension. His shortness of breath had begun 6 months previously and was initially intermittent; it then progressed to constant shortness of breath over the few weeks before presentation. He had no fever, hemoptysis, or chest pain. The patient was admitted to hospital for further evaluation.

Crowdsourcing pneumothorax annotations using machine learning annotations on the NIH chest X-ray dataset.

Pneumothorax is a potentially life-threatening condition that requires prompt recognition and often urgent intervention. In the ICU setting, large numbers of chest radiographs are performed and must be interpreted on a daily basis which may delay diagnosis of this entity. Development of artificial intelligence (AI) techniques to detect pneumothorax could help expedite detection as well as localize and potentially quantify pneumothorax. Open image analysis competitions are useful in advancing state-of-the art AI algorithms but generally require large expert annotated datasets. We have annotated and adjudicated a large dataset of chest radiographs to be made public with the goal of sparking innovation in this space. Because of the cumbersome and time-consuming nature of image labeling, we explored the value of using AI models to generate annotations for review. Utilization of this machine learning annotation (MLA) technique appeared to expedite our annotation process with relatively high sensitivity at the expense of specificity. Further research is required to confirm and better characterize the value of MLAs. Our adjudicated dataset is now available for public consumption in the form of a challenge.

Theoretical and Practical Implications of Treating Cachexia in Advanced Lung Cancer Patients.

Lung cancer continues to be a major worldwide health issue, with more than 50% of patients having incurable metastatic disease at diagnosis. Fortunately, the advanced lung cancer treatment landscape is changing rapidly as a result of the positive impact of effective inhibitors of tumor driver mutations, and the more recent discovery that immune modulation with anti-PD-1/PD-L1 monoclonal antibodies results in tumor regression and prolonged survival. While a relatively small subset of lung cancer patients are candidates for inhibitors of driver mutations, the majority of advanced lung cancer patients are candidates for an immunotherapy regimen. Many of these patients have cachexia, which is associated with increased cancer therapy toxicity and possibly reduced responsiveness to immunotherapy. Two ongoing cachexia trials, one testing a ghrelin analogue and the other testing a multimodal strategy, have endpoints which assess clinical benefit-weight gain and relief of anorexia/cachexia symptoms. Provided that the trial objectives are achieved, these treatment strategies will provide a way to relieve suffering and distress for cachectic cancer patients. While awaiting the results of these trials, it would be reasonable to consider designing studies testing cachexia treatments combined with first-line immunotherapy and chemotherapy-immunotherapy in stage IV lung cancer patients, with enhanced overall survival being one of the endpoints.