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Small cell lung cancer (SCLC) is a highly aggressive malignancy with exceptionally poor prognosis, comprising approximately 15% of lung cancers. Emerging knowledge of the molecular and genomic landscape of SCLC and recent successful clinical applications of new systemic agents have allowed for precision oncology treatment approaches. Imaging is essential for the diagnosis, staging, and treatment monitoring of patients with SCLC. The role of imaging is increasing with the approval of new treatment agents, including immune checkpoint inhibitors, which lead to novel imaging manifestations of response and toxicities. The purpose of this state-of-the-art review is to provide the reader with the latest information about SCLC, focusing on the subtyping of this malignancy (molecular characterization) and the emerging systemic therapeutic approaches and their implications for imaging. The review will also discuss the future directions of SCLC imaging, radiomics and machine learning.

Purpose: ATM is the most commonly mutated DNA damage and repair gene in non–small cell lung cancer (NSCLC); however, limited characterization has been pursued. Experimental Design: Clinicopathologic, genomic, and treatment data were collected for 5,172 patients with NSCLC tumors which underwent genomic profiling. ATM IHC was performed on 182 NSCLCs with ATM mutations. Multiplexed immunofluorescence was performed on a subset of 535 samples to examine tumor-infiltrating immune cell subsets. Results: A total of 562 deleterious ATM mutations were identified in 9.7% of NSCLC samples. ATM-mutant (ATMMUT) NSCLC was significantly associated with female sex (P = 0.02), ever smoking status (P < 0.001), non-squamous histology (P = 0.004), and higher tumor mutational burden (DFCI, P < 0.0001; MSK, P < 0.0001) compared with ATM–wild-type (ATMWT) cases. Among 3,687 NSCLCs with comprehensive genomic profiling, co-occurring KRAS, STK11, and ARID2 oncogenic mutations were significantly enriched among ATMMUT NSCLCs (Q < 0.05), while TP53 and EGFR mutations were enriched in ATMWT NSCLCs. Among 182 ATMMUT samples with ATM IHC, tumors with nonsense, insertions/deletions, or splice site mutations were significantly more likely to display ATM loss by IHC (71.4% vs. 28.6%; P < 0.0001) compared with tumors with only predicted pathogenic missense mutations. Clinical outcomes to PD-(L)1 monotherapy (N = 1,522) and chemo-immunotherapy (N = 951) were similar between ATMMUT and ATMWT NSCLCs. Patients with concurrent ATM/TP53 mutations had significantly improved response rate and progression-free survival with PD-(L)1 monotherapy. Conclusions: Deleterious ATM mutations defined a subset of NSCLC with unique clinicopathologic, genomic, and immunophenotypic features. Our data may serve as resource to guide interpretation of specific ATM mutations in NSCLC.

Supplementary Figure 8. Oncoprint plot showing the distribution of the most commonly mutated genes in NSCLCs with complete ATM loss by IHC (ATMLOST), intact ATM expression (ATMINTACT), and ATM heterogeneous loss (ATMHET LOST) by IHC.

Supplementary Figure 25. (A) Intratumoral, (B) tumor-stroma interface, and (C) total CD8+ PD1+ T cells according to ATM/TP53 co-mutation status. (D) Intratumoral, (E) tumor-stroma interface, and (F) total FOXP3+ immune cells according to ATM/TP53 co-mutation status.

Supplementary Table 6. Baseline clinicopathologic features of patients with ATM mutated NSCLC according ATM protein expression by immunohistochemistry.

Supplementary Figure 15. (A) Objective response rate, (B) progression-free survival, and (C) overall survival to chemo-immunotherapy among patients with advanced/metastatic PD-L1 negative (

Purpose:ATM is the most commonly mutated DNA damage and repair gene in non–small cell lung cancer (NSCLC); however, limited characterization has been pursued.Experimental Design:Clinicopathologic, genomic, and treatment data were collected for 5,172 patients with NSCLC tumors which underwent genomic profiling. ATM IHC was performed on 182 NSCLCs with ATM mutations. Multiplexed immunofluorescence was performed on a subset of 535 samples to examine tumor-infiltrating immune cell subsets.Results:A total of 562 deleterious ATM mutations were identified in 9.7% of NSCLC samples. ATM-mutant (ATMMUT) NSCLC was significantly associated with female sex (P = 0.02), ever smoking status (P < 0.001), non-squamous histology (P = 0.004), and higher tumor mutational burden (DFCI, P < 0.0001; MSK, P < 0.0001) compared with ATM–wild-type (ATMWT) cases. Among 3,687 NSCLCs with comprehensive genomic profiling, co-occurring KRAS, STK11, and ARID2 oncogenic mutations were significantly enriched among ATMMUT NSCLCs (Q < 0.05), while TP53 and EGFR mutations were enriched in ATMWT NSCLCs. Among 182 ATMMUT samples with ATM IHC, tumors with nonsense, insertions/deletions, or splice site mutations were significantly more likely to display ATM loss by IHC (71.4% vs. 28.6%; P < 0.0001) compared with tumors with only predicted pathogenic missense mutations. Clinical outcomes to PD-(L)1 monotherapy (N = 1,522) and chemo-immunotherapy (N = 951) were similar between ATMMUT and ATMWT NSCLCs. Patients with concurrent ATM/TP53 mutations had significantly improved response rate and progression-free survival with PD-(L)1 monotherapy.Conclusions:Deleterious ATM mutations defined a subset of NSCLC with unique clinicopathologic, genomic, and immunophenotypic features. Our data may serve as resource to guide interpretation of specific ATM mutations in NSCLC.

Supplementary Table 1. Baseline clinicopathologic features of the 5172 patients with NSCLC which underwent comprehensive tumor genomic profiling at the Dana-Farber Cancer Institute and Memorial Sloan Kettering Cancer Center.

Supplementary Figure 6. (A) Tumor mutational burden and (B) PD-L1 tumor proportion score distributions according to ATM protein expression by IHC (lost versus intact).

Supplementary Figure 9. (A) Disease free- and overall survival among patients with (A) stage I, and (B) stage II NSCLC according to ATM mutation status.

Supplementary Figure 3. Co-mutation plot showing co-occurrent and mutual exclusive mutations among (A) ATMMUT and (B) ATMWT NSCLCs.

Supplementary Figure 4. (A) Volcano plot showing gene mutations significantly enriched among NSCLCs harboring ATM missense mutations that were predicted to benign in silico versus NSCLCs without any ATM mutation. (B) Volcano plot showing gene mutations significantly enriched among ATMWT and ATMMUT samples in the TCGA-NSCLC cohort.

Supplementary Figure 7. (A) Histograms showing the distribution of deleterious class I and class II ATM mutations with lost or intact ATM protein expression by IHC. (B) Histograms showing the distribution of deleterious missense, nonsense, splice site, and insertion/deletion mutations with lost or intact ATM protein expression by IHC. (C) proportion of NSCLCs with predicted benign and predicted pathogenic ATM missense mutations with lost and intact ATM expression by IHC.

Supplementary Table 4. Baseline clinicopathologic features of patients with ATM mutated NSCLC according ATM protein expression by immunohistochemistry.

Supplementary Table 2. List of potential ATM germline variants identified among 3800 patients with NSCLC at the DFCI

Supplementary Table 5. List of ATM mutations with matched IHC

Supplementary Table 3. Baseline clinicopathologic features of patients with ATMMUT and ATMWT NSCLC at the Dana-Farber Cancer Institute and Memorial Sloan Kettering Cancer Center.

Supplementary Table 7. Baseline clinicopathologic features of patients with ATM mutated and ATM wild-type NSCLCs which underwent multiplexed immunofluorescence at the DFCI.

Recently, advancement of somatostatin receptor (SSTR) imaging and theragnostic approach using peptide receptor radionuclide therapy (PRRT) have changed the paradigm of diagnosis and management of neuroendocrine tumor. 68Ga-DOTATATE PET/CT can diagnose the lung carcinoids with high SSTR expression. With combination of 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT, tumor heterogeneity of lung carcinoid can be identified, which may guide optimal patient selection for PRRT. PRRT may be an effective and safe treatment of advanced lung carcinoids during progression with first-line somatostatin analog therapy. This review provides updates on the diagnosis and management of lung carcinoids, focusing on SSTR imaging and PRRT.

Improved biomarkers are needed to guide the optimal use of autologous stem cell transplantation (ASCT) for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). We hypothesized that minimal residual disease (MRD) identified using immunoglobulin high-throughput sequencing in apheresis stem cell (ASC) samples or post-ASCT peripheral blood mononuclear cell (PBMC) and plasma samples could predict relapse. We studied 159 patients with R/R DLBCL who underwent ASCT, of whom 98 had an ASC sample and 60 had post-ASCT surveillance samples. After a median post-ASCT follow-up of 60 months, the 5-year progression-free survival (PFS) was 48%. MRD was detected in 23/98 (23%) ASC samples and was associated with very poor PFS (5-year PFS 13% vs 53%, p

To evaluate the imaging findings of facial injuries in patients reporting intimate partner violence (IPV).A retrospective review of radiology studies performed for 668 patients reporting IPV to our institution's violence prevention support program identified 96 patients with 152 facial injuries. Demographics, imaging findings, and clinical data obtained from a review of the electronic medical records (EMR) were analyzed to categorize injury patterns.The study cohort consisted of 93 women and 3 men with a mean age of 35 years (range 19-76; median 32). At the time of presentation, 57 (59.3%) patients reported IPV as the mechanism of injury. The most frequent site of injury was the midface, seen in 65 (67.7%) patients. The most common fracture sites were the nasal bones (45/152, 29.6%), followed by the mandible (17/152, 11.1%), and orbits (16/152, 10.5%). Left-sided injuries were more common (90/152; 59.2%). A vast majority of fractures (94.5%) showed minimal or no displacement. Over one-third of injuries (60/152, 39.4%) demonstrated only soft tissue swelling or hematoma without fracture. Associated injuries were seen most frequently in the upper extremity, occurring synchronously in 11 (11.4%) patients, and preceding the index facial injury in 20 (21%) patients./advances in knowledge. The midface was the most frequent location of injury in victims of intimate partner violence, and the nasal bone was the most commonly fractured facial bone. Recognizing these injury patterns can help radiologists suspect IPV and prompt them to discuss the possibility of IPV with the clinical providers.

Immune checkpoint inhibitors (ICI) are widely used in advanced nonsmall cell lung cancer (NSCLC) treatment, and the immune-related adverse events involving many organs have been recognized. This article investigated the incidence and imaging characteristics of immune-related thyroiditis in NSCLC patients and correlated the findings with clinical features. A total of 534 NSCLC patients treated with ICI were included. Imaging findings indicative of thyroiditis included changes in morphology and attenuation on restaging chest CT scans and FDG uptake on PET/CT during ICI therapy. Fifty patients (9.4%) had imaging findings indicative of thyroiditis. The median time to onset was 9.5 weeks (range: 0.9–87.4 weeks). The most common finding was diffuse hypoattenuation of the gland (72%), with enlargement in 15 and atrophy in 12 patients. Heterogeneous attenuation of the gland was noted in 12 patients (24%), with enlargement in 7 and atrophy in 1 patient. Two patients (4%) showed increased FDG uptake in the gland on PET/CT without changes in the CT scan. Twenty-two patients who had both clinical and radiologic diagnoses of thyroiditis were more frequently managed with hormone replacement than those with thyroiditis without an imaging abnormality (p < 0.0001). Therefore, awareness of the imaging findings of immune-related thyroiditis may alert clinicians to the presence of clinically relevant thyroiditis.

To describe the imaging findings of intimate partner violence (IPV)-related injury and to evaluate the role of longitudinal imaging review in detecting IPV.Radiology studies were reviewed in chronological order and IPV-related injuries were recorded among 400 victims of any type of abuse (group 1) and 288 of physical abuse (group 2) from January 2013 to June 2018. The likelihood of IPV was assessed as low/moderate/high based on the review of (1) current and prior anatomically related studies only and (2) longitudinal imaging history consisting of all prior studies. The first radiological study date with moderate/high suspicion was compared to the self-reported date by the victim.A total of 135 victims (33.8%) in group 1 and 144 victims (50%) in group 2 demonstrated IPV-related injuries. Musculoskeletal injury was most common (58.2% and 44.5% in groups 1 and 2, respectively; most commonly lower/upper extremity fractures), followed by neurologic injury (20.9% and 32.9% in groups 1 and 2, respectively; most commonly facial injury). With longitudinal imaging history, radiologists were able to identify IPV in 31% of group 1 and 46.5% of group 2 patients. Amongst these patients, earlier identification by radiologists was provided compared to the self-reported date in 62.3% of group 1 (median, 64 months) and in 52.6% of group 2 (median, 69.3 months).Musculoskeletal and neurological injuries were the most common IPV-related injuries. Knowledge of common injuries and longitudinal imaging history may help IPV identification when victims are not forthcoming.• Musculoskeletal injuries were the most common type of IPV-related injury, followed by neurological injuries. • With longitudinal imaging history, radiologists were able to better raise the suspicion of IPV compared to the selective review of anatomically related studies only. • With longitudinal imaging history, radiologists were able to identify IPV earlier than the self-reported date by a median of 64 months in any type of abuse, and a median of 69.3 months in physical abuse.

This study analyzed national health data to assess convalescent hospital use among female cancer survivors according to age group. This retrospective study collected data from women recovering from breast, colon, and stomach cancer, based on health insurance claim data over 5 years (2013–2017), from the Korea Health Insurance Review and Assessment Service (KHIRA). Interestingly, the number of young and older women who were treated in convalescent hospitals increased every year. In addition, total medical expenses increased in both groups. The annual rate of convalescent hospitalization was higher in older women (8.29~16.39%) than in younger women (4.01~7.46%). The total yearly medical expenses of cancer survivors in convalescent hospitals increased in both age groups and all cancer types, and the range of increase rate was from 7.7% in young breast cancer survivors to 32.2% in young colon cancer survivors. Visit days and days of medication increased noticeably in young colon cancer survivors. Taken together, these data have confirmed the importance of developing standard guidelines for inpatient management in convalescent hospitals and the health management of women cancer survivors by cancer type. This includes establishing a health management system and medical policies.

Fatigue in breast cancer patients undergoing radiotherapy has been studied less comprehensively than fatigue from chemotherapy. The aim of this study was to test the impact of psycho-social factors on the fatigue among breast cancer patients undergoing radiotherapy. This was a cross-sectional correlational study and participants were 210 breast cancer patients currently undergoing radiotherapy in an outpatient setting in Korea. Data collection was carried out from 22 July to 30 September 2019. The results of this study showed that symptom assessment, anxiety and depression, uncertainty, and perceived stress had a direct effect on the fatigue of breast cancer patients receiving radiotherapy, while social support had an indirect effect. These factors explained 67.2% of the fatigue among the participants. This study confirmed that various interventions for symptom assessment, anxiety and depression, uncertainty, and stress reduction need to be developed to reduce fatigue of breast cancer patients receiving radiotherapy. The present results form the basis for developing such interventions.

This study examined anxiety and depression, and their relationship with symptom assessment, uncertainty, social support, and stress in young breast cancer patients receiving radiotherapy.This is a descriptive quantitative study. The participants were 126 patients under 50 years of age with breast cancer undergoing radiotherapy.The anxiety and depression levels were higher among those who were married (t = -2.318, p = .022), non-religious (t = 4.510, p = .005), and had a higher monthly income (F = 2.840, p = .041). The hierarchical regression analysis model included symptom assessment, uncertainty, social support, and stress, and accounted for about 49% of the variance in anxiety and depression (F = 7.688, p .001). Additionally, uncertainty (β = 0.304, p = .001) and stress (β = 0.308, p = .001) were significant predictors of anxiety and depression.Based on the results of this study, nursing interventions are needed to reduce uncertainty and stress in order to reduce anxiety and depression in young breast cancer patients undergoing radiation treatment.