Clinical Intricacies and Advances in Neuroendocrine Tumors: An Organ-Based Multidisciplinary Approach.

ABSTRACT: Neuroendocrine neoplasms (NENs) are rare neoplasms originating from neuroendocrine cells, with increasing incidence due to enhanced detection methods. These tumors display considerable heterogeneity, necessitating diverse management strategies based on factors like organ of origin and tumor size. This article provides a comprehensive overview of therapeutic approaches for NENs, emphasizing the role of imaging in treatment decisions. It categorizes tumors based on their locations: gastric, duodenal, pancreatic, small bowel, colonic, rectal, appendiceal, gallbladder, prostate, lung, gynecological, and others. The piece also elucidates the challenges in managing metastatic disease and controversies surrounding MEN1-neuroendocrine tumor management. The article underscores the significance of individualized treatment plans, underscoring the need for a multidisciplinary approach to ensure optimal patient outcomes.

Sarcopenia, adiposity and large discordance between cystatin C and creatinine-based estimated glomerular filtration rate in patients with cancer.

BACKGROUND: Creatinine-based estimated glomerular filtration rate (eGFRCRE) may overestimate kidney function in patients with sarcopenia. While cystatin C-based eGFR (eGFRCYS) is less affected by muscle mass, it may underestimate kidney function in patients with obesity. We sought to evaluate the relationship between body composition defined by computed tomography (CT) scans and discordance between creatinine, eGFRCRE and eGFRCYS in adult patients with cancer. METHODS: This study is a cross-sectional study of consecutive adults with cancer with an abdominal CT scan performed within 90 days of simultaneous eGFRCRE and eGFRCYS measurements between May 2010 and January 2022. Muscle and adipose tissue cross-sectional areas were measured at the level of the third lumbar vertebral body using a validated deep-learning pipeline. CT-defined sarcopenia was defined using independent sex-specific cut-offs for skeletal muscle index (<39 cm2/m2 for women and <55 cm2/m2 for men). High adiposity was defined as the highest sex-specific quartile of the total (visceral plus subcutaneous) adiposity index in the cohort. The primary outcome was eGFR discordance, defined by eGFRCYS > 30% lower than eGFRCRE; the secondary outcome was eGFRCYS > 50% lower than eGFRCRE. The odds of eGFR discordance were estimated using multivariable logistic regression modelling. Unadjusted spline regression was used to evaluate the relationship between skeletal muscle index and the difference between eGFRCYS and eGFRCRE. RESULTS: Of the 545 included patients (mean age 63 ± 14 years, 300 [55%] females, 440 [80.7%] non-Hispanic white), 320 (58.7%) met the criteria for CT-defined sarcopenia, and 136 (25%) had high adiposity. A total of 259 patients (48%) had >30% eGFR discordance, and 122 (22.4%) had >50% eGFR discordance. After adjustment for potential confounders, CT-defined sarcopenia and high adiposity were both associated with >30% eGFR discordance (adjusted odds ratio [aOR] 1.90, 95% confidence interval [CI] 1.12-3.24; aOR 2.01, 95% CI 1.15-3.52, respectively) and >50% eGFR discordance (aOR 2.34, 95% CI 1.21-4.51; aOR 2.23, 95% CI 1.19-4.17, respectively). A spline model demonstrated that as skeletal muscle index decreases, the predicted difference between eGFRCRE and eGFRCYS widens considerably. CONCLUSIONS: CT-defined sarcopenia and high adiposity are both independently associated with large eGFR discordance. Incorporating valuable information from body composition analysis derived from CT scans performed as a part of routine cancer care can impact the interpretation of GFR estimates.

The relationship between weight gain during chemotherapy and outcomes in patients with advanced non-small cell lung cancer.

BACKGROUND: This post hoc, pooled analysis examined the relationship between different weight gain categories and overall survival (OS) in patients with non-small cell lung cancer (NSCLC) receiving first-line platinum-based chemotherapy. METHODS: Data were pooled from the control arms of three phase III clinical studies (NCT00596830, NCT00254891, and NCT00254904), and the maximum weight gain in the first 3 months from treatment initiation was categorised as >0%, >2.5%, and >5.0%. Cox proportional hazard modelling of OS was used to estimate hazard ratios (HRs) for each category, including baseline covariates, time to weight gain, and time to confirmed objective response (RECIST Version 1.0). RESULTS: Of 1030 patients with advanced NSCLC (IIIB 11.5% and IV 88.5%), 453 (44.0%), 252 (24.5%), and 120 (11.7%) experienced weight gain from baseline of >0%, >2.5%, and >5.0%, respectively. The median time to weight gain was 23 (>0%), 43 (>2.5%), and 45 (>5.0%) days. After adjusting for a time-dependent confirmed objective response, the risk of death was reduced for patients with any weight gain (>0% vs. ≤0% [HR 0.71; 95% confidence interval-CI 0.61, 0.82], >2.5% vs. ≤2.5% [HR 0.76; 95% CI 0.64, 0.91] and >5.0% vs. ≤5.0% [HR 0.77; 95% CI 0.60, 0.99]). The median OS was 13.5 versus 8.6 months (weight gain >0% vs. ≤0%), 14.4 versus 9.4 months (weight gain >2.5% vs. ≤2.5%), and 13.4 versus 10.2 months (weight gain >5.0% vs. ≤5.0%). CONCLUSIONS: Weight gain during treatment was associated with a reduced risk of death, independent of tumour response. The survival benefit was comparable for weight gain >0%, >2.5%, and >5.0%, suggesting that any weight gain may be an early predictor of survival with implications for the design of interventional cancer cachexia studies.

Pack-Year Smoking History: An Inadequate and Biased Measure to Determine Lung Cancer Screening Eligibility.

PURPOSE: Pack-year smoking history is an imperfect and biased measure of cumulative tobacco exposure. The use of pack-year smoking history to determine lung cancer screening eligibility in the current US Preventive Services Task Force (USPSTF) guideline may unintentionally exclude many high-risk individuals, especially those from racial and ethnic minority groups. It is unclear whether using a smoking duration cutoff instead of a smoking pack-year cutoff would improve the selection of individuals for screening. METHODS: We analyzed 49,703 individuals with a smoking history from the Southern Community Cohort Study (SCCS) and 22,126 individuals with a smoking history from the Black Women's Health Study (BWHS) to assess eligibility for screening under the USPSTF guideline versus a proposed guideline that replaces the ≥20-pack-year criterion with a ≥20-year smoking duration criterion. RESULTS: Under the USPSTF guideline, only 57.6% of Black patients with lung cancer in the SCCS would have qualified for screening, whereas a significantly higher percentage of White patients with lung cancer (74.0%) would have qualified (P < .001). Under the proposed guideline, the percentage of Black and White patients with lung cancer who would have qualified for screening increased to 85.3% and 82.0%, respectively, eradicating the disparity in screening eligibility between the groups. In the BWHS, using a 20-year smoking duration cutoff instead of a 20-pack-year cutoff increased the percentage of Black women with lung cancer who would have qualified for screening from 42.5% to 63.8%. CONCLUSION: Use of a 20-year smoking duration cutoff instead of a 20-pack-year cutoff greatly increases the proportion of patients with lung cancer who would qualify for screening and eliminates the racial disparity in screening eligibility between Black versus White individuals; smoking duration has the added benefit of being easier to calculate and being a more precise assessment of smoking exposure compared with pack-year smoking history.

RadioGraphics Update: The 10 Pillars of Lung Cancer Screening-Rationale and Logistics of a Lung Cancer Screening Program.

Editor's Note.-RadioGraphics Update articles supplement or update information found in full-length articles previously published in RadioGraphics. These updates, written by at least one author of the previous article, provide a brief synopsis that emphasizes important new information such as technological advances, revised imaging protocols, new clinical guidelines involving imaging, or updated classification schemes.

A Novel Design-Thinking, Hospital Innovation Core Certificate Curriculum for Radiologists and Trainees: Creation, Implementation, and Multiyear Results.

RATIONALE AND OBJECTIVES: Innovation is a crucial skill for physicians and researchers, yet traditional medical education does not provide instruction or experience to cultivate an innovative mindset. This study evaluates the effectiveness of a novel course implemented in an academic radiology department training program over a 5-year period designed to educate future radiologists on the fundamentals of medical innovation. MATERIALS AND METHODS: A pre- and post-course survey and examination were administered to residents who participated in the innovation course (MESH Core) from 2018 to 2022. Respondents were first evaluated on their subjective comfort level, understanding, and beliefs on innovation-related topics using a 5-point Likert-scale survey. Respondents were also administered a 21-question multiple-choice exam to test their objective knowledge of innovation-related topics. RESULTS: Thirty-eight residents participated in the survey (response rate 95%). Resident understanding, comfort and belief regarding innovation-related topics improved significantly (P < .0001) on all nine Likert-scale questions after the course. After the course, a significant majority of residents either agreed or strongly agreed that technological innovation should be a core competency for the residency curriculum, and that a workshop to prototype their ideas would be beneficial. Performance on the course exam showed significant improvement (48% vs 86%, P < .0001). The overall course experience was rated 5 out of 5 by all participants. CONCLUSION: MESH Core demonstrates long-term success in educating future radiologists on the basic concepts of medical technological innovation. Years later, residents used the knowledge and experience gained from MESH Core to successfully pursue their own inventions and innovative projects. This innovation model may serve as an approach for other institutions to implement training in this domain.

Multimodality Management of Thoracic Tumors: Initial Experience With a Multidisciplinary Thoracic Ablation Conference.

BACKGROUND: This study aimed to describe lesion-specific management of thoracic tumors referred for consideration of image-guided thermal ablation (IGTA) at a newly established multidisciplinary ablation conference. METHODS: This retrospective single-center cohort study included consecutive patients with non-small cell lung cancer (NSCLC) or thoracic metastases evaluated from June 2020 to January 2022 in a multidisciplinary conference. Outcomes included the management recommendation, treatments received (IGTA, surgical resection, stereotactic body radiation therapy [SBRT], multimodality management), and number of tumors treated per patient. Pearson's chi-square test was used to assess for a change in management, and Poisson regression was used to compare the number of tumors by treatment received. RESULTS: The study included 172 patients (58 % female; median age, 69 years; 56 % thoracic metastases; 27 % multifocal primary lung cancer; 59 % ECOG 0 [range, 0-3]) assessed in 206 evaluations. For the patients with NSCLC, IGTA was considered the most appropriate local therapy in 12 %, equal to SBRT in 22 %, and equal to lung resection in 3 % of evaluations. For the patients with thoracic metastases, IGTA was considered the most appropriate local therapy in 22 %, equal to SBRT in 12 %, and equal to lung resection in 3 % of evaluations. Although all patients were referred for consideration of IGTA, less than one third of patients with NSCLC or thoracic metastases underwent IGTA (p < 0.001). Multimodality management allowed for treatment of more tumors per patient than single-modality management (p < 0.01). CONCLUSIONS: Multidisciplinary evaluation of patients with thoracic tumors referred for consideration of IGTA significantly changed patient management and facilitated lesion-specific multimodality management.

High-Frequency Jet Ventilation Versus Spontaneous Respiration for Percutaneous Cryoablation of Lung Tumors: Comparison of Adverse Events and Procedural Efficiency.

BACKGROUND. High-frequency jet ventilation (HFJV) facilitates accurate probe placement in percutaneous ablation of lung tumors but may increase risk for adverse events, including systemic air embolism. OBJECTIVE. The purpose of this study was to compare major adverse events and procedural efficiency of percutaneous lung ablation with HFJV under general anesthesia to spontaneous respiration (SR) under moderate sedation. METHODS. This retrospective study included consecutive adults who underwent CT-guided percutaneous cryoablation of one or more lung tumors with HFJV or SR between January 1, 2017, and May 31, 2023. We compared major adverse events (Common Terminology Criteria for Adverse Events grade ≥ 3) within 30 days postprocedure and hospital length of stay (HLOS) of 2 days or more using logistic regression analysis. We compared procedure time, room time, CT guidance acquisition time, CT guidance radiation dose, total radiation dose, and pneumothorax using generalized estimating equations. RESULTS. Overall, 139 patients (85 women, 54 men; median age, 68 years) with 310 lung tumors (82% metastases) underwent 208 cryoablations (HFJV, n = 129; SR, n = 79). HFJV showed greater rates than SR for the treatment of multiple tumors per session (43% vs 19%, respectively; p = .02) and tumors in a nonperipheral location (48% vs 24%, p < .001). Major adverse event rate was 8% for HFJV and 5% for SR (p = .46). No systemic air embolism occurred. HLOS was 2 days or more in 17% of sessions and did not differ significantly between HFJV and SR (p = .64), including after adjusting for probe number per session, chronic obstructive pulmonary disease, and operator experience (p = .53). Ventilation modalities showed no significant difference in procedure time, CT guidance acquisition time, CT guidance radiation dose, or total radiation dose (all p > .05). Room time was longer for HFJV than SR (median, 154 vs 127 minutes, p < .001). For HFJV, the median anesthesia time was 136 minutes. Ventilation modalities did not differ in the frequencies of pneumothorax or pneumothorax requiring chest tube placement (both p > .05). CONCLUSION. HFJV appears to be as safe as SR but had longer room times. HFJV can be used in complex cases without significantly impacting HLOS of 2 days or more, procedure time, or radiation exposure. CLINICAL IMPACT. Selection of the ventilation modality during percutaneous lung ablation should be based on patient characteristics and anticipated procedural requirements as well as operator preference.

Noninvasive Quantification of Radiation-Induced Lung Injury Using a Targeted Molecular Imaging Probe.

PURPOSE: Radiation-induced lung injury (RILI) is a progressive inflammatory process seen after irradiation for lung cancer. The disease can be insidious, often characterized by acute pneumonitis followed by chronic fibrosis with significant associated morbidity. No therapies are approved for RILI, and accurate disease quantification is a major barrier to improved management. Here, we sought to noninvasively quantify RILI using a molecular imaging probe that specifically targets type 1 collagen in mouse models and patients with confirmed RILI. METHODS AND MATERIALS: Using a murine model of lung radiation, mice were imaged with EP-3533, a type 1 collagen probe, to characterize the development of RILI and to assess disease mitigation after losartan treatment. The human analog probe 68Ga-CBP8, targeting type 1 collagen, was tested on excised human lung tissue containing RILI and was quantified via autoradiography. 68Ga-CBP8 positron emission tomography was used to assess RILI in vivo in 6 human subjects. RESULTS: Murine models demonstrated that probe signal correlated with progressive RILI severity over 6 months. The probe was sensitive to mitigation of RILI by losartan. Excised human lung tissue with RILI had increased binding versus unirradiated control tissue, and 68Ga-CBP8 uptake correlated with collagen proportional area. Human imaging revealed significant 68Ga-CBP8 uptake in areas of RILI and minimal background uptake. CONCLUSIONS: These findings support the ability of a molecular imaging probe targeted at type 1 collagen to detect RILI in preclinical models and human disease, suggesting a role for targeted molecular imaging of collagen in the assessment of RILI.

Ablation of Stage I-II Non-Small Cell Lung Cancer in Patients With Interstitial Lung Disease: A Multicenter Retrospective Study.

BACKGROUND. Treatment options for patients with interstitial lung disease (ILD) who develop stage I-II non-small cell lung cancer (NSCLC) are severely limited, given that surgical resection, radiation, and systemic therapy are associated with significant morbidity and mortality. OBJECTIVE. The aim of this study was to evaluate the safety and efficacy of percutaneous ablation of stage I-II NSCLC in patients with ILD. METHODS. This retrospective study included patients with ILD and stage I-II NSCLC treated with percutaneous ablation in three health systems between October 2004 and February 2023. At each site, a single thoracic radiologist, blinded to clinical outcomes, reviewed preprocedural chest CT examinations for the presence and type of ILD according to 2018 criteria proposed by the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society. The primary outcome was 90-day major (grade ≥ 3) adverse events, based on Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Secondary outcomes were hospital length of stay (HLOS), local tumor control, and overall survival (OS). RESULTS. The study included 33 patients (19 men, 14 women; median age, 78 years; 16 patients with Eastern Cooperative Oncology Group performance status ≤ 1) with ILD who underwent 42 percutaneous ablation sessions (21 cryoablations, 11 radiofrequency ablations, 10 microwave ablations) of 43 NSCLC tumors ((median tumor size, 1.6 cm; IQR, 1.4-2.5 cm; range, 0.7-5.4 cm; 37 stage I, six stage II). The extent of lung fibrosis was 20% or less in 24 patients; 17 patients had imaging findings of definite or probable usual interstitial pneumonia. The 90-day major adverse event rate was 14% (6/42), including one CTCAE grade 4 event. No acute ILD exacerbation or death occurred within 90 days after ablation. The median HLOS was 1 day (IQR, 0-2 days). Median imaging follow-up for local tumor control was 17 months (IQR, 11-32 months). Median imaging or clinical follow-up for OS was 16 months (IQR, 6-26 months). Local tumor control and OS were 78% and 77%, respectively, at 1 year and 73% and 46% at 2 years. CONCLUSION. Percutaneous ablation appears to be a safe and effective treatment option for stage I-II NSCLC in the setting of ILD after multidisciplinary selection. CLINICAL IMPACT. Patients with ILD and stage I-II NSCLC should be considered for percutaneous ablation given that they are frequently ineligible for surgical resection, radiation, and systemic therapy.

Muscle Reference Values From Thoracic and Abdominal CT for Sarcopenia Assessment: The Framingham Heart Study.

BACKGROUND: Loss of muscle mass is a known feature of sarcopenia and predicts poor clinical outcomes. Although muscle metrics can be derived from routine computed tomography (CT) images, sex-specific reference values at multiple vertebral levels over a wide age range are lacking. OBJECTIVE: The aim of this study was to provide reference values for skeletal muscle mass and attenuation on thoracic and abdominal CT scans in the community-based Framingham Heart Study cohort to aid in the identification of sarcopenia. MATERIALS AND METHODS: This secondary analysis of a prospective trial describes muscle metrics by age and sex for participants from the Framingham Heart Study without prior history of cancer who underwent at least 1 CT scan between 2002 and 2011. Using 2 previously validated machine learning algorithms followed by human quality assurance, skeletal muscle was analyzed on a single axial CT image per level at the 5th, 8th, 10th thoracic, and 3rd lumbar vertebral body (T5, T8, T10, L3). Cross-sectional muscle area (cm 2 ), mean skeletal muscle radioattenuation (SMRA, in Hounsfield units), skeletal muscle index (SMI, in cm 2 /m 2 ), and skeletal muscle gauge (SMRA·SMI) were calculated. Measurements were summarized by age group (<45, 45-54, 55-64, 65-74, ≥75 years), sex, and vertebral level. Models enabling the calculation of age-, sex-, and vertebral-level-specific reference values were created and embedded into an open access online Web application. RESULTS: The cohort consisted of 3804 participants (1917 [50.4%] males; mean age, 55.6 ± 11.8 years; range, 33-92 years) and 7162 CT scans. Muscle metrics qualitatively decreased with increasing age and female sex. CONCLUSIONS: This study established age- and sex-specific reference values for CT-based muscle metrics at thoracic and lumbar vertebral levels. These values may be used in future research investigating the role of muscle mass and attenuation in health and disease, and to identify sarcopenia.

Percutaneous Intratumoral Immunoadjuvant Gel Increases the Abscopal Effect of Cryoablation for Checkpoint Inhibitor Resistant Cancer.

Percutaneous cryoablation is a common clinical therapy for metastatic and primary cancer. There are rare clinical reports of cryoablation inducing regression of distant metastases, known as the "abscopal" effect. Intratumoral immunoadjuvants may be able to augment the abscopal rate of cryoablation, but existing intratumoral therapies suffer from the need for frequent injections and inability to confirm target delivery, leading to poor clinical trial outcomes. To address these shortcomings, an injectable thermoresponsive gel-based controlled release formulation is developed for the FDA-approved Toll-like-receptor 7 (TLR7) agonist imiquimod ("Imigel") that forms a tumor-resident depot upon injection and contains a contrast agent for visualization under computed tomography (CT). The poly-lactic-co-glycolic acid-polyethylene glycol-poly-lactic-co-glycolic acid (PLGA-PEG-PLGA)-based amphiphilic copolymer gel's underlying micellar nature enables high drug concentration and a logarithmic release profile that is additive with the neo-antigen release from cryoablation, requiring only a single injection. Rheological testing demonstrated the thermoresponsive increase in viscosity at body temperature and radio-opacity via microCT. Its ability to significantly augment the abscopal rate of cryoablation is demonstrated in otherwise immunotherapy resistant metastatic tumors in two aggressive colorectal and breast cancer dual tumor models with an all or nothing response, responders generally demonstrating complete regression of bilateral tumors in 90-day survival studies.

Role of sex in lung cancer risk prediction based on single low-dose chest computed tomography.

A validated open-source deep-learning algorithm called Sybil can accurately predict long-term lung cancer risk from a single low-dose chest computed tomography (LDCT). However, Sybil was trained on a majority-male cohort. Use of artificial intelligence algorithms trained on imbalanced cohorts may lead to inequitable outcomes in real-world settings. We aimed to study whether Sybil predicts lung cancer risk equally regardless of sex. We analyzed 10,573 LDCTs from 6127 consecutive lung cancer screening participants across a health system between 2015 and 2021. Sybil achieved AUCs of 0.89 (95% CI: 0.85-0.93) for females and 0.89 (95% CI: 0.85-0.94) for males at 1 year, p = 0.92. At 6 years, the AUC was 0.87 (95% CI: 0.83-0.93) for females and 0.79 (95% CI: 0.72-0.86) for males, p = 0.01. In conclusion, Sybil can accurately predict future lung cancer risk in females and males in a real-world setting and performs better in females than in males for predicting 6-year lung cancer risk.

Artificial Intelligence and Machine Learning in Lung Cancer Screening.

Recent advances in artificial intelligence and machine learning (AI/ML) hold substantial promise to address some of the current challenges in lung cancer screening and improve health equity. This article reviews the status and future directions of AI/ML tools in the lung cancer screening workflow, focusing on determining screening eligibility, radiation dose reduction and image denoising for low-dose chest computed tomography (CT), lung nodule detection, lung nodule classification, and determining optimal screening intervals. AI/ML tools can assess for chronic diseases on CT, which creates opportunities to improve population health through opportunistic screening.

Noninvasive Quantification of Radiation-Induced Lung Injury using a Targeted Molecular Imaging Probe.

Rationale: Radiation-induced lung injury (RILI) is a progressive inflammatory process commonly seen following irradiation for lung cancer. The disease can be insidious, often characterized by acute pneumonitis followed by chronic fibrosis with significant associated morbidity. No therapies are approved for RILI, and accurate disease quantification is a major barrier to improved management. Objective: To noninvasively quantify RILI, utilizing a molecular imaging probe that specifically targets type 1 collagen in mouse models and patients with confirmed RILI. Methods: Using a murine model of lung radiation, mice were imaged with EP-3533, a type 1 collagen probe to characterize the development of RILI and to assess disease mitigation following losartan treatment. The human analog probe targeted against type 1 collagen, 68Ga-CBP8, was tested on excised human lung tissue containing RILI and quantified via autoradiography. Finally, 68Ga-CBP8 PET was used to assess RILI in vivo in six human subjects. Results: Murine models demonstrated that probe signal correlated with progressive RILI severity over six-months. The probe was sensitive to mitigation of RILI by losartan. Excised human lung tissue with RILI had increased binding vs unirradiated control tissue and 68Ga-CBP8 uptake correlated with collagen proportional area. Human imaging revealed significant 68Ga-CBP8 uptake in areas of RILI and minimal background uptake. Conclusions: These findings support the ability of a molecular imaging probe targeted at type 1 collagen to detect RILI in preclinical models and human disease, suggesting a role for targeted molecular imaging of collagen in the assessment of RILI.Clinical trial registered with www.clinicaltrials.gov (NCT04485286, NCT03535545).

Impact of Baseline Interstitial Lung Abnormalities on Pneumonitis Risk in Patients Receiving Immune Checkpoint Inhibitors for Non-Small-Cell Lung Cancer.

INTRODUCTION/BACKGROUND: Immune-related pneumonitis is a potentially fatal complication of treatment with immune checkpoint inhibitors (ICIs). Interstitial lung disease (ILD) is associated with increased risk for pneumonitis, but the impact of interstitial abnormalities (ILA) in the absence of ILD has not been extensively assessed. We examined the relationship between ILA on pretreatment chest computed tomography (CT) scans and risk of pneumonitis in patients with non-small-cell lung cancer (NSCLC). METHODS: This retrospective cohort study included consecutive adult patients who received ICI for NSCLC between January 2013 and January 2020 at our institution. Two thoracic radiologists blinded to clinical outcomes independently reviewed pre-ICI chest CTs to identify and categorize ILA using previously published definitions. We used uni- and multivariable analysis adjusted for age, radiation, and smoking status to assess for associations between ILA, clinicopathologic characteristics, and symptomatic (CTCAE grade ≥2) pneumonitis. RESULTS: Of 475 patients who received ICI treatment and met inclusion criteria, baseline ILA were present in 78 (16.4%) patients, most commonly as a subpleural nonfibrotic pattern. In total, 43 (9.1%) of 475 patients developed symptomatic pneumonitis. Pneumonitis occurred in 16.7% of patients with ILA compared to 7.6% patients without ILA (P < .05). Presence of ground glass and extent of lung parenchymal involvement were associated with an increased risk of pneumonitis. On multivariable analysis, baseline ILA remained associated with increased risk of symptomatic pneumonitis (OR 2.2, 95% CI, 1.0-4.5). CONCLUSIONS: Baseline ILAs are associated with the development of symptomatic pneumonitis in patients with NSCLC treated with ICI. Additional studies are needed to validate these observations.

Multimodality local ablative therapy of 23 lung metastases with surgical resection and percutaneous cryoablation in a patient with Li-Fraumeni Syndrome: A case report.

Patients with Li-Fraumeni syndrome (LFS) are prone to develop a variety of malignancies due to insufficient activity of the encoded tumor suppressor protein P53, including adrenocortical carcinoma, breast cancer, lung cancer, pancreatic cancer, and sarcoma. In the setting of LFS, local treatment options for lung metastases are limited to surgery and thermal ablation since radiotherapy and some systemic therapies predispose patients to additional future malignancies. We present the case of a 45-year-old woman with LFS with leiomyosarcoma metastases to both lungs who underwent bilateral wedge resections to treat a total of eight lung metastases followed by six percutaneous cryoablation sessions to treat 15 additional lung metastases over a period of 24 months. Our case demonstrates the option of multimodal local ablative therapies for lung metastases in patients with LFS, including percutaneous cryoablation.