Are there features that can predict the unresectability of pleural mesothelioma?

INTRODUCTION: The current clinical staging of pleural mesothelioma (PM) is often discordant with the pathologic staging. This study aimed to identify clinical and radiological features that could help predict unresectability in PM. METHODS: Twenty-two descriptive radiologic features were retrospectively evaluated on preoperative computed tomography (CT) and/or positron emission tomography/CT (PET/CT) performed in patients with presumably resectable PM who underwent surgery. Measurements of maximum and sum pleural thickness at three levels of the thorax (upper, middle, and lower) were taken and stratified based on the cutpoints provided by the International Association for the Study of Lung Cancer (IASLC). Clinical and radiological features, including clinical-stage, were compared between resectable and unresectable tumors by univariate analysis and logistic regression modeling. RESULTS: Of 133 patients, 69/133 (52%) had resectable and 64/133 (48%) had unresectable PM. Asbestos exposure (p = 0.005), neoadjuvant treatment (p = 0.001), clinical T-stage (p < 0.0001), all pleural thickness measurements (p < 0.05), pleural thickness pattern (p < 0.0001) and degree (p = 0.033), lung invasion (p = 0.004), extrapleural space obliteration (p < 0.0001), extension to subphrenic space (p = 0.0004), and two combination variables representing extensive diaphragmatic contact and/or chest wall involvement (p = 0.002) and mediastinal invasion (p < 0.0001) were significant predictors at univariate analysis. At multivariable analysis, all models achieved a strong diagnostic performance (area under the curve (AUC) > 0.8). The two best-performing models were one that included the upper-level maximum pleural thickness, extrapleural space obliteration, and mediastinal infiltration (AUC = 0.876), and another that integrated clinical variables and radiological assessment through the clinical T-stage (AUC = 0.879). CONCLUSION: Selected clinical and radiologic features, including pleural thickness measurements, appear to be strong predictors of unresectability in PM. CLINICAL RELEVANCE STATEMENT: A more accurate prediction of unresectability in the preoperative assessment of patients with pleural mesothelioma may avoid unnecessary surgery and prompt initiation of nonsurgical treatments. KEY POINTS: About half of pleural mesothelioma patients are reported to receive an incorrect disease stage preoperatively. Eleven features identified as predictors of unresectability were included in strongly performing predictive models. More accurate preoperative staging will help clinicians and patients choose the most appropriate treatments.

Imaging Follow-Up of Nonsurgical Therapies for Lung Cancer: AJR Expert Panel Narrative Review.

Lung cancer continues to be the most common cause of cancer-related death worldwide. In the past decade, with the implementation of lung cancer screening programs and advances in surgical and nonsurgical therapies, the survival of patients with lung cancer has increased, as has the number of imaging studies that these patients undergo. However, most patients with lung cancer do not undergo surgical re-section, because they have comorbid disease or lung cancer in an advanced stage at diagnosis. Nonsurgical therapies have continued to evolve with a growing range of systemic and targeted therapies, and there has been an associated evolution in the imaging findings encountered at follow-up examinations after such therapies (e.g., with respect to posttreatment changes, treatment complications, and recurrent tumor). This AJR Expert Panel Narrative Review describes the current status of nonsurgical therapies for lung cancer and their expected and unexpected imaging manifestations. The goal is to provide guidance to radiologists regarding imaging assessment after such therapies, focusing mainly on non-small cell lung cancer. Covered therapies include systemic therapy (conventional chemotherapy, targeted therapy, and immunotherapy), radiotherapy, and thermal ablation.

CT-based Radiogenomic Analysis of Clinical Stage I Lung Adenocarcinoma with Histopathologic Features and Oncologic Outcomes.

Background A preoperative predictive model is needed that can be used to identify patients with lung adenocarcinoma (LUAD) who have a higher risk of recurrence or metastasis. Purpose To investigate associations between CT-based radiomic consensus clustering of stage I LUAD and clinical-pathologic features, genomic data, and patient outcomes. Materials and Methods Patients who underwent complete surgical resection for LUAD from April 2014 to December 2017 with preoperative CT and next-generation sequencing data were retrospectively identified. Comprehensive radiomic analysis was performed on preoperative CT images; tumors were classified as solid, ground glass, or mixed. Patients were clustered into groups based on their radiomics features using consensus clustering, and clusters were compared with tumor genomic alterations, histopathologic features, and recurrence-specific survival (Kruskal-Wallis test for continuous data, χ2 or Fisher exact test for categorical data, and log-rank test for recurrence-specific survival). Cluster analysis was performed on the entire cohort and on the solid, ground-glass, and mixed lesion subgroups. Results In total, 219 patients were included in the study (median age, 68 years; interquartile range, 63-74 years; 150 [68%] women). Four radiomic clusters were identified. Cluster 1 was associated with lepidic, acinar, and papillary subtypes (76 of 90 [84%]); clusters 2 (13 of 50 [26%]) and 4 (13 of 45 [29%]) were associated with solid and micropapillary subtypes (P < .001). The EGFR alterations were highest in cluster 1 (38 of 90 [42%], P = .004). Clusters 2, 3, and 4 were associated with lymphovascular invasion (19 of 50 [38%], 14 of 34 [41%], and 28 of 45 [62%], respectively; P < .001) and tumor spread through air spaces (32 of 50 [64%], 21 of 34 [62%], and 31 of 45 [69%], respectively; P < .001). STK11 alterations (14 of 45 [31%]; P = .006), phosphoinositide 3-kinase pathway alterations (22 of 45 [49%], P < .001), and risk of recurrence (log-rank P < .001) were highest in cluster 4. Conclusion CT-based radiomic consensus clustering enabled identification of associations between radiomic features and clinicalpathologic and genomic features and outcomes in patients with clinical stage I lung adenocarcinoma. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Nishino in this issue.

COVID-19 in patients with cancer: can baseline radiologic severity and early evolution predict clinical outcomes?

OBJECTIVE: To determine whether the degree of parenchymal involvement on chest radiograph (CXR) at the time of COVID-19 diagnosis and its early radiologic evolution can predict adverse events including hospitalization, intubation, and death in patients with cancer. METHODS: Retrospective study of 627 COVID-19-positive patients between March and April 2020, of which 248 had baseline CXR within 72 h of diagnosis and 64 patients had follow-up wihtin72 h. CXRs were classified as abnormal (i.e., radiologic findings suggestive of COVID-19 infection were noted), normal, or indeterminate. Baseline and follow-up severity scores were calculated based on lung regions in abnormal CXRs. Statistical analysis was performed to determine associations between abnormal CXR or severity score with adverse events. RESULTS: Of 248 patients (median age = 65) with a baseline CXR, 172/248 (69%) had an abnormal baseline study, which was associated with hospitalization (p < 0.001), intubation (p = 0.001), and death (p = 0.005). For patients with solid neoplasms, when adjusted for stage, it was associated with hospitalization (p = 0.0002), intubation (p = 0.019), and death (p = 0.03). The median baseline severity score was 3 (range = 1-10); the greater the score, the higher the likelihood of adverse outcome (p < 0.003 for all). A baseline severity score > 9 predicted > 50% probability of intubation and a score of ≥ 10 predicted > 50% of probability of death. The baseline severity score was not correlated with cancer-related treatment. Early radiologic progression was not correlated with hospitalization, intubation, or death. CONCLUSION: The degree of parenchymal involvement on CXR within 72 h of COVID-19 diagnosis is associated with adverse outcomes in patients with cancer. KEY POINTS: • In patients with cancer, the presence and severity of radiologic manifestation of COVID-19 on chest radiographs within 72 h of COVID-19 diagnosis are associated with hospitalization, intubation, and death. • Early radiologic progression on chest radiographs is not correlated with adverse outcomes.

Lung cancer screening in patients with previous malignancy: Is this cohort at increased risk for malignancy?

OBJECTIVES: To determine the rate of second primary lung cancer (SPLC) and describe the clinical characteristics and radiological findings in individuals with a prior history of cancer presenting to a low-dose computed tomography (LDCT) lung cancer screening program at a tertiary cancer center. METHODS: Patients with a previous history of malignancy, a life expectancy ≥ 5 years referred for CT lung cancer screening between May 2, 2011, and November 28, 2018, were included. Demographics regarding risk factors including smoking history and prior history of thoracic radiation were collected. CT scan features assessed nodule size, morphologic features, and number. The Lung-CT Reporting and Data System (Lung-RADS) scoring system was retrospectively applied to studies performed before October 2014 and prospectively applied to remainder of studies. Data was collected in a Health Insurance Portability and Accountability Act (HIPAA)-compliant manner. RESULTS: A total of 543 patients were studied (mean age of 66 years). All had a previous history of cancer, most commonly breast cancer 205 (38%), head and neck cancer 105 (19%), and lung cancer 87 (16%). Of screening CTs performed, 17.5% were positive screening study results as per Lung-RADS scoring system. SPLC was diagnosed in 35 patients (6.4%) with 21 prevalence cancers detected and 14 interval cancers detected in subsequent screening rounds. CONCLUSIONS: The rate of screen-detected SPLC in patients with prior malignancy is higher than reported rates seen in historical prospective screening studies. Our study suggests the need for prospective research to evaluate any mortality benefit that screening may have in this population. KEY POINTS: • The rate of screen-detected second primary lung cancer in patients with prior malignancy is higher than reported rates seen in historical prospective randomized lung cancer screening studies in a general screened population. • Patients with a prior malignancy undergoing lung cancer screening have higher rates of positive screening studies and higher rates of invasive diagnostic procedures than those reported in a general screening population. • Prospective research is required to evaluate if screening offers a mortality benefit in this population.

Perfusion defects on dual-energy CTA in patients with suspected pulmonary embolism correlate with right heart strain and lower survival.

OBJECTIVES: To evaluate the utility of perfusion defects on dual-energy CT angiograms (DECTA) in assessing the clinical severity of pulmonary embolism (PE). METHODS: We retrospectively reviewed 1136 consecutive diagnostic DECTA exams performed on patients with suspected PE between January 2014 and September 2014. Presence and location of obstructive and non-obstructive PE, right ventricular to left ventricular ratio (RV/LV ratio), and inferior vena cava (IVC) backflow were recorded. Iodine maps were reviewed to establish the presence of perfusion defect and its extent was determined through a score-based segmental impaired perfusion. Subsequently, the perfusion defect scores were correlated with clinical parameters including vital signs, electrocardiogram (ECG) abnormalities, echocardiogram findings, troponin, and brain natriuretic peptide (bnp) levels. Clinical information regarding primary cancer diagnosis, oncologic stage, and date of death if applicable was also recorded. RESULTS: Of the 1136 diagnostic iodine maps, 96 of these patients had perfusion defects on iodine maps. After uni- and multivariate analysis, significant correlation was found between the presence of a perfusion defect and RV/LV ratio (p = 0.05), IVC backflow (p = 0.03), elevated troponin (p = 0.03), and right heart dysfunction as determined on an echocardiogram (p = 0.05). The greater the perfusion defect score, the higher the likelihood of IVC backflow (p = 0.005) and obstructive PE (p = 0.002). When adjusted for oncologic stage, patients with a perfusion defect and a higher perfusion defect score had a higher mortality rate (p = 0.005). CONCLUSION: The presence of a perfusion defect correlates with several parameters evaluating PE severity. A perfusion defect and higher perfusion defect score were associated with a lower survival. KEY POINTS: • Detection of perfusion defects on dual-energy CT angiograms and its extent correlates with right heart strain in the setting of pulmonary embolism. • The presence and extent of a perfusion defect in patients with pulmonary embolism are associated with lower survival.

Risk stratification of cardiac metastases using late gadolinium enhancement cardiovascular magnetic resonance: prognostic impact of hypo-enhancement evidenced tumor avascularity.

BACKGROUND: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) is widely used to identify cardiac neoplasms, for which diagnosis is predicated on enhancement stemming from lesion vascularity: Impact of contrast-enhancement pattern on clinical outcomes is unknown. The objective of this study was to determine whether cardiac metastasis (CMET) enhancement pattern on LGE-CMR impacts prognosis, with focus on heterogeneous lesion enhancement as a marker of tumor avascularity. METHODS: Advanced (stage IV) systemic cancer patients with and without CMET matched (1:1) by cancer etiology underwent a standardized CMR protocol. CMET was identified via established LGE-CMR criteria based on lesion enhancement; enhancement pattern was further classified as heterogeneous (enhancing and non-enhancing components) or diffuse and assessed via quantitative (contrast-to-noise ratio (CNR); signal-to-noise ratio (SNR)) analyses. Embolic events and mortality were tested in relation to lesion location and contrast-enhancement pattern. RESULTS: 224 patients were studied, including 112 patients with CMET and unaffected (CMET -) controls matched for systemic cancer etiology/stage. CMET enhancement pattern varied (53% heterogeneous, 47% diffuse). Quantitative analyses were consistent with lesion classification; CNR was higher and SNR lower in heterogeneously enhancing CMET (p < 0.001)-paralleled by larger size based on linear dimensions (p < 0.05). Contrast-enhancement pattern did not vary based on lesion location (p = NS). Embolic events were similar between patients with diffuse and heterogeneous lesions (p = NS) but varied by location: Patients with right-sided lesions had threefold more pulmonary emboli (20% vs. 6%, p = 0.02); those with left-sided lesions had lower rates equivalent to controls (4% vs. 5%, p = 1.00). Mortality was higher among patients with CMET (hazard ratio [HR] = 1.64 [CI 1.17-2.29], p = 0.004) compared to controls, but varied by contrast-enhancement pattern: Diffusely enhancing CMET had equivalent mortality to controls (p = 0.21) whereas prognosis was worse with heterogeneous CMET (p = 0.005) and more strongly predicted by heterogeneous enhancement (HR = 1.97 [CI 1.23-3.15], p = 0.005) than lesion size (HR = 1.11 per 10 cm [CI 0.53-2.33], p = 0.79). CONCLUSIONS: Contrast-enhancement pattern and location of CMET on CMR impacts prognosis. Embolic events vary by CMET location, with likelihood of PE greatest with right-sided lesions. Heterogeneous enhancement-a marker of tumor avascularity on LGE-CMR-is a novel marker of increased mortality risk.

Management of Pulmonary Nodules in Oncologic Patients: AJR Expert Panel Narrative Review.

Cancer survivors are at higher risk than the general population for development of a new primary malignancy, most commonly lung cancer. Current lung cancer screening guidelines recommend low-dose chest CT for high-risk individuals, including patients with a history of cancer and a qualifying smoking history. However, major lung cancer screening trials have inconsistently included cancer survivors, and few studies have assessed management of lung nodules in this population. This narrative review highlights relevant literature and provides expert opinion for management of pulmonary nodules detected incidentally or by screening in oncologic patients. In patients with previously treated lung cancer, a new nodule most likely represents distant metastasis from the initial lung cancer or a second primary lung cancer; CT features such as nodule size and composition should guide decisions regarding biopsy, PET/CT, and CT surveillance. In patients with extrapulmonary cancers, nodule management requires individualized risk assessment; smoking is associated with increased odds of primary lung cancer, whereas specific primary cancer types are associated with increased odds of pulmonary metastasis. Nonneoplastic causes, such as infection, medication toxicity, and postradiation or postsurgical change, should also be considered. Future prospective studies are warranted to provide evidence-based data to assist clinical decision-making in this context.

Use of a portable computed tomography scanner for chest imaging of COVID-19 patients in the urgent care at a tertiary cancer center.

To present a novel use of a portable computed tomography (CT) for evaluation of COVID-19 patients presenting to an urgent care center (UCC). Infection control is imperative for hospitals treating patients with COVID-19, even more so in cancer centers, where the majority of the patient population is susceptible to adverse outcomes from the infection. Over the past several weeks, our department has worked to repurpose a portable CT scanner from our surgical colleagues that operates with fixed-parameters to perform non-contrast, helical, thin-slice chest imaging to address the known pulmonary complications of COVID-19. Despite the technical limitations of the portable CT unit that was repurposed for the UCC, diagnostic-quality images in an acute care setting were successfully obtained. Repurposing of a portable CT scanner for use in COVID-19 patients offers a feasible option to obtain diagnostic quality images while minimizing the risk of exposing other patients and hospital staff to an infected patient.

Computed tomography features of local pleural recurrence in patients with malignant pleural mesothelioma treated with intensity-modulated pleural radiation therapy.

OBJECTIVE: This study was conducted in order to describe the computed tomography (CT) features of local pleural recurrence in patients with malignant pleural mesothelioma undergoing intensity-modulated pleural radiation therapy (IMPRINT) as part of multimodality treatment. METHODS: In this observational study, 58 patients treated with IMPRINT between September 21, 2004, and December 1, 2014 were included. Baseline and follow-up CT scans were qualitatively assessed. On follow-up scans, pleural thickening was categorized as unchanged, decreased, or new/increased. New/increased pleural abnormality was subcategorized as diffuse smooth pleural thickening, diffuse nodular pleural thickening, focal pleural nodule, or multiple pleural nodules. To identify features more frequently present at the time of local recurrence, follow-up scans with local recurrence were matched to four control scans; exact conditional logistic regression was performed. RESULTS: Twenty-one (36%) patients had local pleural recurrence and 20 (34%) patients had nonpleural recurrence; 3 patients had both types of recurrence. The 1-year cumulative incidence rate of local recurrence was 27% (95% confidence interval 15, 39). On follow-up scans, three patterns of pleural abnormality were significantly associated with local recurrence: new/increased multiple pleural nodules (10 (48%) positive scans vs 0 control scans), new/increased diffuse nodular pleural thickening (7 (33%) positive scans vs 1 (1%) control scans), and new/increased focal pleural nodule (3 (14%) positive scans vs 1 (1%) control scan) (p < 0.001 for all). CONCLUSIONS: Multiple new/increased pleural nodules are the feature most commonly present at local recurrence following IMPRINT; however, any pattern of increased nodular pleural thickening is suspicious. KEY POINTS: • In patients with mesothelioma receiving intensity-modulated pleural radiation as part of multimodality therapy, increasing multiple pleural nodules is the computed tomography feature most commonly present at local recurrence. • In these patients, any CT pattern of increased nodular pleural thickening should be considered suspicious for local recurrence. • The most common sites of nonpleural recurrence were lung parenchyma, thoracic lymph nodes, and peritoneum.

Advances in oncologic imaging: update on 5 common cancers.

Imaging has become a pivotal component throughout a patient's encounter with cancer, from initial disease detection and characterization through treatment response assessment and posttreatment follow-up. Recent progress in imaging technology has presented new opportunities for improving clinical care. This article provides updates on the latest approaches to imaging of 5 common cancers: breast, lung, prostate, and colorectal cancers, and lymphoma.

Dual-Energy CT Angiography for Detection of Pulmonary Emboli: Incremental Benefit of Iodine Maps.

Purpose To determine if there is added benefit of using iodine maps from dual-energy (DE) CT in addition to conventional CT angiography images to diagnose pulmonary embolism (PE). Materials and Methods In this retrospective analysis, 1144 consecutive dual-energy CT angiography examinations performed from January through September 2014 at an oncologic referral center to evaluate for PE were reviewed. The 1144 examinations included 1035 patients (mean age, 58.7 years; range, 15-99 years). First, the location, level, and type (occlusive vs nonocclusive) of PEs on conventional CT angiograms were recorded. Iodine maps were then reviewed for defects suggestive of PE. Last, CT angiograms were rereviewed to detect additional PEs suggested by the iodine map. Consensus reviews were performed for examinations with PEs. The confidence interval of percentages was calculated by using the Clopper-Pearson method. Results On 147 of 1144 (12.8%) CT angiograms, a total of 372 PEs were detected at initial review. After review of the DE CT iodine map, 27 additional PEs were found on 26 of 1144 CT angiograms (2.3%; 95% confidence interval [CI]: 1.5%, 3.3%). Of the 27 additional PEs, six (22.2%) were segmental, 21 (77.8%) were subsegmental, 24 (88.9%) were occlusive, and three (11.1%) were nonocclusive. Eleven of 1144 (1.0%; 95% CI: 0.5%, 1.7%) CT angiograms had a new diagnosis of PE after review of the DE CT iodine maps. Conclusion Dual-energy CT iodine maps show a small incremental benefit for the detection of occlusive segmental and subsegmental pulmonary emboli. © RSNA, 2018.

Malignant Pleural Mesothelioma: Are There Imaging Characteristics Associated With Different Histologic Subtypes on Computed Tomography?

OBJECTIVES: Determine imaging characteristics specific to epithelioid (eMPM), sarcomatoid (sMPM), and biphasic (bMPM) subtypes of malignant pleural mesothelioma (MPM) on computed tomography. METHODS: Preoperative computed tomography scans of patients with MPM were retrospectively assessed for numerous features including primary affected side, volume loss, pleural thickness, pleural calcifications, pleural effusion, and lymphadenopathy. RESULTS: One hundred twenty-five patients with MPM were included. Histologic subdivision was 97 eMPM (77%), 17 bMPM (14%), and 11 sMPM (9%). Nonepithelioid MPM (bMPM and sMPM) was more likely than eMPM to have calcified pleural plaques (P = 0.035). Analyzed separately, bMPM and sMPM each demonstrated calcified plaques more frequently than eMPM, and sMPM more often had internal mammary nodes; however, P values did not reach significance (P = 0.075 and 0.071, respectively). CONCLUSIONS: Calcified plaques are significantly more common in nonepithelioid subtypes compared with eMPM. Given the different prognoses and management of MPM subtypes, accurate noninvasive subtype classification is clinically vital.

Computed Tomographic Appearance of Organizing Pneumonia in an Oncologic Patient Population.

OBJECTIVE: The aims of this study were to describe the computed tomographic features of organizing pneumonia (OP) in an oncologic patient population and to also identify features associated with lung cancer and patients undergoing hematopoietic stem cell transplant (HSCT). METHODS: In retrospective computed tomographies from 151 patients with pathologically confirmed OP between January 2009 and September 2014, number of lesions, location, size, margin type, and consistency, as well as volume of lymphadenopathy and the presence and size of pleural effusions, were recorded. Associated malignancy was noted. RESULTS: Organizing pneumonia most commonly presented as a diffuse process (n = 62, 41%), frequently occupied both a central and peripheral location (n = 79, 53%), and commonly presented with a solid appearance (n = 67, 44%) or with ground glass opacity (n = 80, 53%). Pleural effusions were seen in 68 patients (45%). Organizing pneumonia less frequently contained air bronchograms, cavitation, necrosis, surrounding ground glass opacity, or adjacent bronchiectasis. In patients with lung cancer (n = 25, 17%), OP more likely presented as discrete lesions and occupied a peripheral location as compared with patients with other malignancies (Ps = 0.025 and 0.002). In HSCT patients (n = 29, 19%), a diffuse process was more commonly seen than in non-HSCT patients (P = 0.038). CONCLUSIONS: Organizing pneumonia more commonly presents as discrete lesions with a peripheral location in patients with lung cancer and as a diffuse process in patients who had undergone HSCT.

Cabozantinib in patients with advanced RET-rearranged non-small-cell lung cancer: an open-label, single-centre, phase 2, single-arm trial.

BACKGROUND: RET rearrangements are found in 1-2% of non-small-cell lung cancers. Cabozantinib is a multikinase inhibitor with activity against RET that produced a 10% overall response in unselected patients with lung cancers. To assess the activity of cabozantinib in patients with RET-rearranged lung cancers, we did a prospective phase 2 trial in this molecular subgroup. METHODS: We enrolled patients in this open-label, Simon two-stage, single-centre, phase 2, single-arm trial in the USA if they met the following criteria: metastatic or unresectable lung cancer harbouring a RET rearrangement, Karnofsky performance status higher than 70, and measurable disease. Patients were given 60 mg of cabozantinib orally per day. The primary objective was to determine the overall response (Response Criteria Evaluation in Solid Tumors version 1.1) in assessable patients; those who received at least one dose of cabozantinib, and had been given CT imaging at baseline and at least one protocol-specified follow-up timepoint. We did safety analyses in the modified intention-to-treat population who received at least one dose of cabozantinib. The accrual of patients with RET-rearranged lung cancer to this protocol has been completed but the trial is still ongoing because several patients remain on active treatment. This study was registered with ClinicalTrials.gov, number NCT01639508. FINDINGS: Between July 13, 2012, and April 30, 2016, 26 patients with RET-rearranged lung adenocarcinomas were enrolled and given cabozantinib; 25 patients were assessable for a response. KIF5B-RET was the predominant fusion type identified in 16 (62%) patients. The study met its primary endpoint, with confirmed partial responses seen in seven of 25 response-assessable patients (overall response 28%, 95% CI 12-49). Of the 26 patients given cabozantinib, the most common grade 3 treatment-related adverse events were lipase elevation in four (15%) patients, increased alanine aminotransferase in two (8%) patients, increased aspartate aminotransferase in two (8%) patients, decreased platelet count in two (8%) patients, and hypophosphataemia in two (8%) patients. No drug-related deaths were recorded but 16 (62%) patients died during the course of follow-up. 19 (73%) patients required dose reductions due to drug-related adverse events. INTERPRETATION: The reported activity of cabozantinib in patients with RET-rearranged lung cancers defines RET rearrangements as actionable drivers in patients with lung cancers. An improved understanding of tumour biology and novel therapeutic approaches will be needed to improve outcomes with RET-directed targeted treatment. FUNDING: Exelixis, National Institutes of Health and National Cancer Institute Cancer Center Support Grant P30 CA008748.

Foundational Segmentation Models and Clinical Data Mining Enable Accurate Computer Vision for Lung Cancer.

This study aims to assess the effectiveness of integrating Segment Anything Model (SAM) and its variant MedSAM into the automated mining, object detection, and segmentation (MODS) methodology for developing robust lung cancer detection and segmentation models without post hoc labeling of training images. In a retrospective analysis, 10,000 chest computed tomography scans from patients with lung cancer were mined. Line measurement annotations were converted to bounding boxes, excluding boxes < 1 cm or > 7 cm. The You Only Look Once object detection architecture was used for teacher-student learning to label unannotated lesions on the training images. Subsequently, a final tumor detection model was trained and employed with SAM and MedSAM for tumor segmentation. Model performance was assessed on a manually annotated test dataset, with additional evaluations conducted on an external lung cancer dataset before and after detection model fine-tuning. Bootstrap resampling was used to calculate 95% confidence intervals. Data mining yielded 10,789 line annotations, resulting in 5403 training boxes. The baseline detection model achieved an internal F1 score of 0.847, improving to 0.860 after self-labeling. Tumor segmentation using the final detection model attained internal Dice similarity coefficients (DSCs) of 0.842 (SAM) and 0.822 (MedSAM). After fine-tuning, external validation showed an F1 of 0.832 and DSCs of 0.802 (SAM) and 0.804 (MedSAM). Integrating foundational segmentation models into the MODS framework results in high-performing lung cancer detection and segmentation models using only mined clinical data. Both SAM and MedSAM hold promise as foundational segmentation models for radiology images.

Clinical outcomes of stereotactic body radiation therapy for malignant pleural mesothelioma.

BACKGROUND: The objective of this study is to determine the outcomes and toxicities of patients with malignant pleural mesothelioma (MPM) treated with stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: Data were extracted from an institutional tumor registry for patients diagnosed with mesothelioma and treated with SBRT. Kaplan-Meier and Cox regression analyses were employed to determine local control (LC) and overall survival (OS). RESULTS: Forty-four patients with 59 total treated tumors from December 2006 to April 2022 were identified. Fifty-one (86.4 %) cases had oligoprogressive disease (five sites or less). The median prescription dose delivered was 3000 cGy in 5 fractions (range: 2700-6000 cGy in 3-8 fractions). Fifty-one (86.4 %) tumors were in the pleura, 4 (6.8 %) spine, 2 (3.4 %) bone, 1 (1.7 %) brain, and 1 (1.7 %) pancreas. The median follow-up from SBRT completion for those alive at last follow-up was 28 months (range: 14-52 months). The most common toxicities were fatigue (50.8 %), nausea (22.0 %), pain flare (15.3 %), esophagitis (6.8 %), dermatitis (6.8 %), and pneumonitis (5.1 %). There were no grade ≥ 3 acute or late toxicities. There were 2 (3.4 %) local failures, one of the pleura and another of the spine. One-year LC was 92.9 % (95 % CI: 74.6-98.2 %) for all lesions and 96.3 % (95 % CI: 76.5-99.5 %) for pleural tumors. One-year LC was 90.9 % (95 % CI: 68.1-97.6 %) for epithelioid tumors and 92.1 % (95 % CI: 72.1-98.0 %) for oligoprogressive tumors. One-year OS from time of SBRT completion was 36.4 % (95 % CI: 22.6-50.3 %). On multivariable analysis, KPS was the lone significant predictor for OS (p = 0.029). CONCLUSIONS: Our single-institutional experience on patients with MPM suggests that SBRT is safe with a low toxicity profile and potentially achieve good local control.

A Phase I/II Study of Valemetostat (DS-3201b), an EZH1/2 Inhibitor, in Combination with Irinotecan in Patients with Recurrent Small-Cell Lung Cancer.

PURPOSE: Recurrent small-cell lung cancer (SCLC) has few effective treatments. The EZH2-SLFN11 pathway is a driver of acquired chemoresistance that may be targeted. PATIENTS AND METHODS: This phase I/II trial investigated valemetostat, an EZH1/2 inhibitor, with fixed-dose irinotecan in patients with recurrent SCLC. Phase I primary objectives were to assess safety, tolerability, and a recommended phase II dose (RP2D). The phase II primary objective was overall response rate (ORR), with secondary objectives of determining duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Correlative analyses included immunohistochemistry of pretreatment and on-treatment tumor biopsies and pharmacokinetics analysis. RESULTS: Twenty-two patients were enrolled (phase I, n = 12; phase II, n = 10); one withdrew consent prior to treatment. Three dose-limiting toxicities (DLT) in dose-escalation resulted in valemetostat 100 mg orally daily selected as RP2D. Among 21 evaluable patients, the most frequent (≥20%) treatment-related adverse events were diarrhea, fatigue, nausea, and rash; three patients discontinued treatment for toxicity. Three of the first 10 patients in phase II experienced DLTs triggering a stopping rule. The ORR was 4/19 or 21% [95% confidence interval (CI), 6%-46%]. The median DoR, PFS, and OS were 4.6 months, 2.2 months (95% CI, 1.3-7.6 months), and 6.6 months (95% CI, 4.3 to not reached), respectively. SLFN11/EZH2 expression and SCLC subtyping markers did not correlate with response, but MHC-I expression did increase with treatment. Two responders demonstrated subtype switching on treatment. CONCLUSIONS: Combination valemetostat and irinotecan was not tolerated but demonstrated efficacy in recurrent SCLC. Valemetostat, combined with agents without overlapping toxicity, warrants further investigation in SCLC.

Early Circulating Tumor DNA Shedding Kinetics for Prediction of Platinum Sensitivity in Patients With Small Cell Lung Cancer.

PURPOSE: Small cell lung cancer (SCLC) is characterized by rapid progression after platinum resistance. Circulating tumor (ctDNA) dynamics early in treatment may help determine platinum sensitivity. MATERIALS AND METHODS: Serial plasma samples were collected from patients receiving platinum-based chemotherapy for SCLC on the first 3 days of cycle one and on the first days of subsequent cycles with paired samples collected both before and again after infusions. Tumor-informed plasma analysis was carried out using CAncer Personalized Profiling by deep Sequencing (CAPP-Seq). The mean variant allele frequency (VAF) of all pretreatment mutations was tracked in subsequent blood draws and correlated with radiologic response. RESULTS: ctDNA kinetics were assessed in 122 samples from 21 patients. Pretreatment VAF did not differ significantly between patients who did and did not respond to chemotherapy (mean 22.5% v 4.6%, P = .17). A slight increase in ctDNA on cycle 1, day 1 immediately post-treatment was seen in six of the seven patients with available draws (fold change from baseline: 1.01-1.44), half of whom achieved a response. All patients who responded had a >2-fold decrease in mean VAF on cycle 2 day 1 (C2D1). Progression-free survival (PFS) and overall survival (OS) were significantly longer in patients with a >2-fold decrease in mean VAF after one treatment cycle (6.8 v 2.6 months, log-rank P = .0004 and 21.7 v 6.4 months, log rank P = .04, respectively). CONCLUSION: A >2-fold decrease in ctDNA concentration was observed by C2D1 in all patients who were sensitive to platinum-based therapy and was associated with longer PFS and OS.

A Real-World Assessment of Stage I Lung Cancer Through Electronic Nose Technology.

INTRODUCTION: Electronic nose (E-nose) technology has reported excellent sensitivity and specificity in the setting of lung cancer screening. However, the performance of E-nose specifically for early-stage tumors remains unclear. Therefore, the aim of our study was to assess the diagnostic performance of E-nose technology in clinical stage I lung cancer. METHODS: This phase IIc trial (NCT04734145) included patients diagnosed with a single greater than or equal to 50% solid stage I nodule. Exhalates were prospectively collected from January 2020 to August 2023. Blinded bioengineers analyzed the exhalates, using E-nose technology to determine the probability of malignancy. Patients were stratified into three risk groups (low-risk, [<0.2]; moderate-risk, [≥0.2-0.7]; high-risk, [≥0.7]). The primary outcome was the diagnostic performance of E-nose versus histopathology (accuracy and F1 score). The secondary outcome was the clinical performance of the E-nose versus clinicoradiological prediction models. RESULTS: Based on the predefined cutoff (<0.20), E-nose agreed with histopathologic results in 86% of cases, achieving an F1 score of 92.5%, based on 86 true positives, two false negatives, and 12 false positives (n = 100). E-nose would refer fewer patients with malignant nodules to observation (low-risk: 2 versus 9 and 11, respectively; p = 0.028 and p = 0.011) than would the Swensen and Brock models and more patients with malignant nodules to treatment without biopsy (high-risk: 27 versus 19 and 6, respectively; p = 0.057 and p < 0.001). CONCLUSIONS: In the setting of clinical stage I lung cancer, E-nose agrees well with histopathology. Accordingly, E-nose technology can be used in addition to imaging or as part of a "multiomics" platform.