Comparison of a Risk Calculator With Frailty Indices in Patients Undergoing Lung Cancer Resection.

INTRODUCTION: While frailty has gained attention for its utility in risk stratification, no studies have directly compared them to existing risk calculators. The objective of this study was to compare the risk stratification of the American College of Surgeons Surgical Risk Calculator (ACS-SRC), the Revised Risk Analysis Index (RAI-rev), and the Modified Frailty Index (5-mFI). The primary outcomes were 30-day postoperative morbidity, 30-day postoperative mortality, unplanned readmission, unplanned reoperation, and discharge disposition other than home. METHODS: Patients undergoing anatomic lung resection for primary, nonsmall cell lung cancer were identified within the ACS National Quality Improvement Program (ACS NSQIP) database. Tools were compared for discrimination in the primary outcomes. RESULTS: 9663 patients undergoing anatomic lung resection for cancer between 2012 and 2014 were included. The cohort was 53.1% female. Median age at diagnosis was 67 (IQR 59-74) years. Perioperative morbidity and mortality rates were 10.9% (n = 1048) and 1.6% (n = 158). Rates of 30-day postoperative unplanned readmission and reoperation were 7.5% (n = 725) and 4.8% (n = 468). The ACS-SRC had the highest discrimination for all measured outcomes, as measured by the area under the receiver operating curve (AUC) and corresponding confidence interval (95% CI). This included perioperative mortality (AUC 0.74, 95% CI 0.71-0.78), compared to RAI-rev (AUC 0.66, 95% CI 0.62-0.69) and 5-mFI (AUC 0.61, 95% CI 0.57-0.65; p < 0.001). The RAI-rev and 5-mFI had similar discrimination for all measured outcomes. CONCLUSION: ACS-SRC was the perioperative risk stratification tool with the highest predictive discrimination for adverse, 30-day, postoperative events for patients with cancer treated with anatomic lung resection.

Unique Ovarian Metastasis of Small-Cell Lung Cancer and Complete Response After Chemo-Immunotherapy: An Unusual Spread as a Predictor Factor.

A 41-year-old woman, never-smoker, accessed the emergency room for an episode of hemoptysis in September 2019. CT scan showed a defect of opacification in the left pulmonary artery and a solid mass of 12 cm in the left annex. PET confirmed high metabolic activity in the ovarian mass and, surprisingly, in the left hilar lung. The patient underwent a left annessiectomy and the histological examination showed a metastasis of small-cell lung cancer (SCLC) that mimicked a primary ovarian cancer. Fibrobronchoscopy and echo-guided biopsy confirmed the diagnosis of pulmonary SCLC. From January 2020, we started systemic therapy with carboplatin, etoposide, and atezolizumab. After six cycles of induction therapy with a complete response, thoracic and prophylactic cranial radiotherapy was done and maintenance therapy with atezolizumab was administered. After 53 months, the patient is still under treatment with a complete radiological response. This case report describes a rare instance of ovarian metastasis from SCLC that responded exceptionally well to immunotherapy. By reviewing literature from 1950 to the present, we identified other cases of ovarian metastases from SCLC, highlighting shared clinical and pathological traits and distinguishing them from primary ovarian tumors. We also examined the potential mechanisms behind the prolonged immunotherapy response observed in this case. As research on SCLC and immunotherapy evolves, this case may offer valuable insights into prognostic and predictive factors for this typically fatal cancer.

Cardiovascular disease in thymic cancer patients.

Introduction: Cancer patients may have increased risk for adverse cardiac events, but our understanding of cardiovascular risk in thymic cancer patients is not clear. We sought to characterize baseline cardiometabolic risk factors before thymic cancer diagnosis and the potential association between cancer treatment and subsequent cardiac events. Methods: This was a retrospective cohort study evaluating patients with thymic cancer from 2003 to 2020 compared to age- and sex-matched controls without cancer. Baseline cardiovascular risk factors, cancer characteristics, and incidence of cardiac events were collected from the health information exchange. Multivariable regression was used to examine the impact of cardiovascular risk factors and cancer therapies. Results: We compared 296 patients with pathology-confirmed thymic cancer to 2,960 noncancer controls. Prior to cancer diagnosis, thymic cancer patients (TCPs) had lower prevalence of hypertension, dyslipidemia, and diabetes mellitus and similar rates of obesity, tobacco use, and pre-existing cardiovascular disease (CVD) compared to controls. After diagnosis, high-risk TCPs (>2 cardiovascular risk factors or pre-existing CVD) had higher risk for cardiac events (HR 3.73, 95% CI 2.88-4.83, p < 0.001). In the first 3 years after diagnosis, TCPs had higher incidence of cardiac events (HR 1.38, 95% CI 1.01-1.87, p = 0.042). High-risk TCPs who received radiotherapy or chemotherapy had higher risk of cardiac events (HR 4.99, 95% CI 2.30-10.81, p < 0.001; HR 6.24, 95% CI 2.84-13.72, p < 0.001). Discussion/conclusion: Compared to noncancer controls, TCPs experienced more cardiac events when adjusted for risk factors. Patients with multiple cardiovascular risk factors receiving radiotherapy or chemotherapy had higher incidence of cardiac events.

Comparison of a risk calculator with frailty indices in patients undergoing lung cancer resection.

INTRODUCTION: Perioperative risk stratification is an essential component of preoperative planning for cancer surgery. While frailty has gained attention for its utility in risk stratification, no studies have directly compared it to existing risk calculators. Therefore, the objective of this study was to compare the risk stratification of the American College of Surgeons Surgical Risk Calculator (ACS-SRC), the Revised Risk Analysis Index (RAI-rev), and the Modified Frailty Index (5-mFI). The primary outcomes were 30-day postoperative morbidity, 30-day postoperative mortality, unplanned readmission, unplanned reoperation, and discharge disposition other-than-home. METHODS: Patients undergoing anatomic lung resection for primary, non-small cell lung cancer were identified within the American College of Surgeons National Quality Improvement Program (ACS NSQIP) database. The ACS-SRC, RAI-rev, and 5-mFI tools were used to predict adverse postoperative events. Tools were compared for discrimination in the primary outcomes. RESULTS: 9663 patients undergoing anatomic lung resection for cancer between 2012 and 2014 were included. The cohort was 53.1% female. Median age at diagnosis was 67 (interquartile range = 59-74) years. Cardiothoracic surgeons performed 89% and general surgeons performed 11.0% of the operations. Perioperative morbidity and mortality rates were 10.9% (n = 1048) and 1.6% (n = 158). Rates of 30-day postoperative unplanned readmission and reoperation were 7.5% (n = 725) and 4.8% (n = 468). The ACS-SRC had the highest discrimination for all measured outcomes, as measured by the area under the receiver operating curve (AUC) and corresponding confidence interval (95% confidence interval [CI]). This included perioperative mortality (AUC = 0.74, 95% CI = 0.71-0.78), compared to RAI-rev (AUC = 0.66, 95% CI = 0.62-0.69) and 5-mFI (AUC = 0.61, 95% CI = 0.57-0.65; p < 0.001). The RAI-rev and 5-mFI had similar discrimination for all measured outcomes. CONCLUSION: ACS-SRC was the perioperative risk stratification tool with the highest predictive discrimination for adverse, 30-day, postoperative events for patients with cancer treated with anatomic lung resection.

Circulating tumor cells: advancing personalized therapy in small cell lung cancer patients.

Small cell lung cancer (SCLC) is a highly aggressive cancer with a dismal 5-year survival of < 7%, despite the addition of immunotherapy to first-line chemotherapy. Specific tumor biomarkers, such as delta-like ligand 3 (DLL3) and schlafen11 (SLFN11), may enable the selection of more efficacious, novel immunomodulating targeted treatments like bispecific T-cell engaging monoclonal antibodies (tarlatamab) and chemotherapy with PARP inhibitors. However, obtaining a tissue biopsy sample can be challenging in SCLC. Circulating tumor cells (CTCs) have the potential to provide molecular insights into a patient's cancer through a "simple" blood test. CTCs have been studied for their prognostic ability in SCLC; however, their value in guiding treatment decisions is yet to be elucidated. This review explores novel and promising targeted therapies in SCLC, summarizes current knowledge of CTCs in SCLC, and discusses how CTCs can be utilized for precision medicine.

Trends and Disparities in Robotic Surgery Utilization for Non-Small Cell Lung Cancer.

INTRODUCTION: Robotic surgery has become an increasingly utilized approach for resectable lung cancer. However, availability may be limited for certain patient populations, underscoring inequity in access to innovative surgical techniques. We hypothesize that there is an association between social determinants of health and robotic surgery utilization for resectable non-small cell lung cancer (NSCLC). METHODS: We queried the National Cancer Database (2010-2019) for patients with clinical stage I-III NSCLC who underwent resection, stratifying the cohort based on surgical technique. Multivariable logistic regression analysis was performed to identify associations between sociodemographic and clinicopathologic factors and the robotic approach. RESULTS: Among the 226,455 clinical stage I-III NSCLC patients identified, 34,059 (15%) received robotic resections, 78,039 (34.5%) underwent thoracoscopic resections, and 114,357 (50.5%) had open resections. Robotic surgery utilization increased from 3.1% in 2010 to 34% in 2019 (P < 0.001). Despite this, after adjusting by clinical stage, extent of resection, site of tumor, and receipt of neoadjuvant therapy, multivariable analysis revealed various sociodemographic and treatment facility factors that were associated with underutilization of this approach: lack of insurance (adjusted odds ratio [aOR] 0.83, 95% confidence interval [CI] 0.73-0.93), lower income brackets (aOR 0.93, 95% CI 0.91-0.96), provincial settings (urban aOR 0.79, 95% CI 0.76-0.82; rural aOR 0.57, 95% CI 0.51-0.64), and treatment at community centers (comprehensive community cancer programs aOR 0.73, 95% CI 0.70-0.75; community cancer programs aOR 0.51, 95% CI 0.47-0.55). CONCLUSIONS: This study suggests that disparities in determinants of health influence accessibility to robotic surgery for resectable NSCLC. Identification of these gaps is crucial to target vulnerable sectors of the population in promoting equality and uniformity in surgical treatment.

Trends and comparative outcomes between operative approaches for segmentectomy in lung cancer.

BACKGROUND: Segmentectomy is increasingly performed for non-small cell lung cancer. However, comparative outcomes data among open, robotic-assisted, and video-assisted thoracoscopic approaches are limited. METHODS: A retrospective cohort study of non-small cell lung cancer segmentectomy cases (2013-2021) from the Society of Thoracic Surgeons General Thoracic Surgery Database was performed. Baseline characteristics were balanced using inverse probability of treatment weighting and compared by operative approach. Volume trends, outcomes, and nodal upstaging were assessed. RESULTS: Of 9927 patients who underwent segmentectomy, 84.8% underwent minimally invasive surgery, with robotic-assisted thoracoscopic surgery becoming the most common approach in 2019. Open segmentectomy is more likely to be performed at low-volume centers (P < .0001), whereas robotic-assisted thoracoscopic surgery is more likely to be performed at high-volume centers (P < .0001). Video-assisted thoracoscopic surgery had a higher open conversion rate than robotic-assisted thoracoscopic surgery (odds ratio, 11.8; CI, 7.01-21.6; P < .001). Minimally invasive surgery had less 30-day morbidity compared with open segmentectomy (video-assisted thoracoscopic surgery odds ratio, 0.71; 95% CI, 0.55-0.94; P = .013; robotic-assisted thoracoscopic surgery odds ratio, 0.59; CI, 0.43-0.81; P = .001). The number of nodes and stations harvested were highest for robotic-assisted thoracoscopic surgery; however, N1 upstaging was more likely in open compared with robotic-assisted thoracoscopic surgery (odds ratio, 0.63; CI, 0.45-0.89; P < .007) and video-assisted thoracoscopic surgery (odds ratio, 0.61; CI, 0.46-0.83; P = .001). CONCLUSIONS: Segmentectomy volume has increased considerably, with robotic-assisted thoracoscopic surgery becoming the most common approach. Minimally invasive surgery has less major morbidity compared with open segmentectomy, with no difference between video-assisted thoracoscopic surgery and robotic-assisted thoracoscopic surgery. However, risk of open conversion is higher with video-assisted thoracoscopic surgery. Robotic-assisted thoracoscopic surgery had increased nodal harvest, whereas hilar nodal upstaging was highest with thoracotomy. This study reveals significant differences in outcomes exist between segmentectomy operative approach; the impact of approach on survival merits further investigation.

Stereotactic Body Radiotherapy for Centrally Located Inoperable Early-Stage NSCLC: EORTC 22113-08113 LungTech Phase II Trial Results.

INTRODUCTION: The international phase II single-arm LungTech trial 22113-08113 of the European Organization for Research and Treatment of Cancer assessed the safety and efficacy of stereotactic body radiotherapy (SBRT) in patients with centrally located early-stage NSCLC. METHODS: Patients with inoperable non-metastatic central NSCLC (T1-T3 N0 M0, ≤7cm) were included. After prospective central imaging review and radiation therapy quality assurance for any eligible patient, SBRT (8 × 7.5 Gy) was delivered. The primary endpoint was freedom from local progression probability three years after the start of SBRT. RESULTS: The trial was closed early due to poor accrual related to repeated safety-related pauses in recruitment. Between August 2015 and December 2017, 39 patients from six European countries were included and 31 were treated per protocol and analyzed. Patients were mainly male (58%) with a median age of 75 years. Baseline comorbidities were mainly respiratory (68%) and cardiac (48%). Median tumor size was 2.6 cm (range 1.2-5.5) and most cancers were T1 (51.6%) or T2a (38.7%) N0 M0 and of squamous cell origin (48.4%). Six patients (19.4%) had an ultracentral tumor location. The median follow-up was 3.6 years. The rates of 3-year freedom from local progression and overall survival were 81.5% (90% confidence interval [CI]: 62.7%-91.4%) and 61.1% (90% CI: 44.1%-74.4%), respectively. Cumulative incidence rates of local, regional, and distant progression at three years were 6.7% (90% CI: 1.6%-17.1%), 3.3% (90% CI: 0.4%-12.4%), and 29.8% (90% CI: 16.8%-44.1%), respectively. SBRT-related acute adverse events and late adverse events ≥ G3 were reported in 6.5% (n = 2, including one G5 pneumonitis in a patient with prior interstitial lung disease) and 19.4% (n = 6, including one lethal hemoptysis after a lung biopsy in a patient receiving anticoagulants), respectively. CONCLUSIONS: The LungTech trial suggests that SBRT with 8 × 7.5Gy for central lung tumors in inoperable patients is associated with acceptable local control rates. However, late severe adverse events may occur after completion of treatment. This SBRT regimen is a viable treatment option after a thorough risk-benefit discussion with patients. To minimize potentially fatal toxicity, careful management of dose constraints, and post-SBRT interventions is crucial.

Malignant phyllodes tumor of the breast with predominant osteosarcoma and chondrosarcomatous differentiation: a rare case report and review of literature.

Background: Phyllodes tumors (PTs), which account for less than 1% of mammary gland tumors, composed of both epithelial and stromal components. If a malignant heterologous component is encountered, PT is considered malignant. Malignant phyllodes tumors (MPTs) only account for 8% to 20% of PTs. We report a case of MPT with osteosarcoma and chondrosarcoma differentiation and review the literature to discuss the differential diagnosis and therapy. Case presentation: A 59-year-old Chinese woman come to our hospital because of a palpable mass she had had for 1 months in the left breast. Preoperative core needle biopsy (CNB) was performed on the left breast mass on January 11, 2023. Pathological diagnosis was malignant tumor, the specific type was not clear. Mastectomy and sentinel lymph node biopsy of the left breast was performed. No metastasis was found in 3 sentinel lymph nodes identified by carbon nanoparticles and methylene blue double staining. Heterologous osteosarcoma and chondrosarcomatous differentiation of phyllodes tumor were observed. Immunohistochemistry: spindle tumor cells ER(-), PR(-), HER-2(-), CK-pan(-), CK7(-), CK8(-), SOX10(-), S100(-), and MDM2(-), CK5/6(-), P63(-), P40(-) were all negative. CD34:(+), SATB2(+), P53(90% strong), CD68 (+), Ki-67(LI: about 60%). No ductal carcinoma in situ was found in the breast. Fluorescence in situ hybridization (FISH) indicated USP6 was negatively expressed on formalin-fixed, paraffin-embedded (FFPE) tissue sections. Conclusion: MPTs are rare, and heterologous differentiation in MPTs is exceedingly rare. It could be diagnosed by pathology when metaplastic carcinoma, primary osteosarcoma, or myositis ossificans were excluded. This case could help clinicians to improve the prognosis and treatment of this disease.

Outpatient Embedded Palliative Care for Patients with Advanced Thoracic Malignancy: A Retrospective Cohort Study.

Although cancer care is often contextualized in terms of survival, there are other important cancer care outcomes, such as quality of life and cost of care. The ASCO Value Framework assesses the value of cancer therapies not only in terms of survival but also with consideration of quality of life and financial cost. Early palliative care for patients with advanced cancer is associated with improved quality of life, mood, symptoms, and overall survival for patients, as well as cost savings. While palliative care has been shown to have numerous benefits, the impact of real-world implementation of outpatient embedded palliative care on value-based metrics is not fully understood. We sought to describe the association between outpatient embedded palliative care in a multidisciplinary thoracic oncology clinic and inpatient value-based metrics. We performed a retrospective cohort study of 215 patients being treated for advanced thoracic malignancies with non-curative intent. We evaluated the association between outpatient embedded palliative care and inpatient clinical outcomes including emergency room visits, hospitalizations, intensive care unit admissions, hospital charges, as well as hospital quality metrics including 30-day readmissions, admissions within 30 days of death, inpatient mortality, and inpatient hospital charges. Outpatient embedded palliative care was associated with lower hospital charges per day (USD 3807 vs. USD 4695, p = 0.024). Furthermore, patients who received outpatient embedded palliative care had lower hospital admissions within 30 days of death (O.R. 0.45; 95% CI 0.29, 0.68; p < 0.001) and a lower inpatient mortality rate (IRR 0.67; 95% CI 0.48, 0.95; p = 0.024). Our study further supports that outpatient palliative care is a high-value intervention and alternative models of palliative care, including one embedded into a multidisciplinary thoracic oncology clinic, is associated with improved value-based metrics.

Major vascular reconstructions in thoracic oncological surgery.

The replacement of the superior vena cava and thoracic outlet vessels for thoracic malignancies often becomes necessary for radical oncological surgery. The pulmonary artery can be directly infiltrated by the tumor or affected by metastatic hilar lymph nodes. In some cases, it must be resected and reconstructed to achieve oncological radicality and/or avoid pneumonectomy. This study reflects a single-surgeon, retrospective experience spanning 6 years (2017-2023). We reviewed data from patients undergoing early anticoagulant therapy after superior vena cava or thoracic outlet vessels bypass and from patients undergoing early antiaggregation therapy following pulmonary artery reconstruction or resection. This series comprises 41 patients treated by a single surgeon. Fourteen patients underwent superior vena cava and thoracic outlet vessel procedures. Among these, eight patients received superior vena cava replacement (six for thymic malignancies and two for lung cancer), and six patients underwent jugular and subclavian artery/vein resection or replacement (all six had sarcomas). There was one death due to respiratory failure, not associated with bleeding or bypass closure. Additionally, there was one graft closure in a patient with severe coagulopathy and three instances of hemothorax (two patients had undiagnosed complex coagulopathies not evident in pre-operative routine blood tests). Following bleeding incidents, anticoagulation was initiated the next day in one case and based on hematological indications in the two coagulopathic patients. In the pulmonary artery series, 27 patients were involved: 20 underwent direct suture after tangential resection, and 7 received pericardial patch reconstruction. Only one case experienced bleeding necessitating redo-surgery. All these patients received early and chronic antiaggregation therapy after pulmonary artery reconstruction. We conclude that major thoracic oncological vascular surgery is safe and feasible with appropriate technical skills. However, achieving optimal results requires integration with correct early anticoagulant therapy or antiaggregation to maintain the patency of bypasses/grafts and prevent life-threatening risks associated with closure of the "new vessels."

Nivolumab in pretreated pleural mesothelioma: Results from an observational real-world study of patients treated within the AIFA 5% Fund.

BACKGROUND: Pleural mesothelioma is a rare cancer with a dismal prognosis and few therapeutic options, especially in the pretreated setting. Immunotherapy with checkpoint inhibitors as single agents yielded interesting results in refractory pleural mesothelioma, achieving a response rate between 10-20%, median progression-free survival of 2-5 months and median overall survival of 7-13 months. PATIENTS AND METHODS: A retrospective, multi-institutional study of pleural mesothelioma patients treated with nivolumab in second and further line was performed. The endpoints of the study are response rate, disease control rate, progression free survival and overall survival. RESULTS: Sixty-five patients with pleural mesothelioma treated with nivolumab in second and further line were enrolled at seven Italian institutions. The response rate was 8%, disease control rate was 37%, median progression free survival was 5.7 months (95% CI: 2.9-9.0) and median overall survival was 11.1 (95% CI 6.2-19.9) months. A higher neutrophils and neutrophils to lymphocytes ratio at baseline were associated with worse prognosis. CONCLUSION: Nivolumab as a single agent is fairly active in a cohort of unselected pretreated pleural mesothelioma patients. Further investigations on clinical and translational factors are needed to define which patient might benefit most from nivolumab treatment in pleural mesothelioma.

Transitioning to Neoadjuvant Therapy for Resectable Non-Small Cell Lung Cancer: Trends and Surgical Outcomes in a Regionalized Pulmonary Oncology Network.

BACKGROUND: Several regulatory agencies have approved the use of the neoadjuvant chemo-immunotherapy for resectable stage II and III of non-small cell lung cancer (NSCLC) and numerous trials investigating novel agents are underway. However, significant concerns exist around the feasibility and safety of offering curative surgery to patients treated within such pathways. The goal in this study was to evaluate the impact of a transition towards a large-scale neoadjuvant therapy program for NSCLC. METHODS: Medical charts of patients with clinical stage II and III NSCLC who underwent resection from January 2015 to December 2020 were reviewed. The primary outcome was perioperative complication rate between neoadjuvant-treated versus upfront surgery patients. Multivariable logistic regression estimated occurrence of postoperative complications and overall survival was assessed as an exploratory secondary outcome by Kaplan-Meier and Cox-regression analyses. RESULTS: Of the 428 patients included, 106 (24.8%) received neoadjuvant therapy and 322 (75.2%) upfront surgery. Frequency of minor and major postoperative complications was similar between groups (P = .22). Occurrence in postoperative complication was similar in both cohort (aOR = 1.31, 95% CI 0.73-2.34). Neoadjuvant therapy administration increased from 10% to 45% with a rise in targeted and immuno-therapies over time, accompanied by a reduced rate of preoperative radiation therapy use. 1-, 2-, and 5-year overall survival was higher in neoadjuvant therapy compared to upfront surgery patients (Log-Rank P = .017). CONCLUSIONS: No significant differences in perioperative outcomes and survival were observed in resectable NSCLC patients treated by neoadjuvant therapy versus upfront surgery. Transition to neoadjuvant therapy among resectable NSCLC patients is safe and feasible from a surgical perspective.

Innovations in Thoracic Oncology and the Promise of Liquid Biopsies with Dr. Luis Raez.

Thoracic oncology continues to pose a great threat to human health as one of the most common forms of cancer. Liquid biopsies present a transformative approach to treating patients affected by these types of diseases by providing a less invasive genetic overview of the tumor, aiding in both diagnostic and treatment measures. The primary objective of this article is to examine the prospects of liquid biopsies in managing thoracic malignancies and to present barriers to their usage as demonstrated by Dr. Luis Raez. In examining why molecular diagnostics continue to be employed together with more traditional methods, this article presents the next steps in the clinical application of blood-based cancer screening. Future cancer diagnosis and treatment aim to prioritize circulating biomarker analyses based on their potential for the detection and monitoring of thoracic cancers. Liquid biopsies are favored thanks to their reduced invasiveness with respect to traditional treatments. The further study of clinical biomarkers and technological advancements are thus pivotal to enhance the clinical applicability of this method. In conclusion, this blood-based analysis offers a promising route by which the diagnosis, treatments, and outcomes of thoracic cancer can be improved.

Alk-rearranged lung adenocarcinoma: From molecular genetics to therapeutic targeting.

Anaplastic Lymphoma Kinase (ALK) is a potent oncogenic driver of lung adenocarcinoma (LUAD). ALK is constitutively activated by gene fusion events between the ALK and other gene fusion partners in about 2-3% of LUADs, characterized by few other gene alterations. ALK-fusions are a druggable target through potent pharmacological inhibitors of tyrosine kinase activity. Thus, several ALK-TKIs (Tyrosine Kinase Inhibitors) of first-, second- and third-generation have been developed that improved the outcomes of ALK-rearranged LUADs when used as first- or second-line agents. However, resistance mechanisms greatly limit the durability of the therapeutic effects elicited by these TKIs. The molecular mechanisms responsible for these resistance mechanisms have been in part elucidated, but overcoming acquired resistance to ALK-derived therapy remains a great challenge. Some new therapeutic strategies under investigation aim to induce long-term remission in ALK-fusion positive LUADs.

Thoracic Applications of Spectral CT Scan.

TOPIC IMPORTANCE: Thoracic imaging with CT scan has become an essential component in the evaluation of respiratory and thoracic diseases. Providers have historically used conventional single-energy CT; however, prevalence of dual-energy CT (DECT) is increasing, and as such, it is important for thoracic physicians to recognize the utility and limitations of this technology. REVIEW FINDINGS: The technical aspects of DECT are presented, and practical approaches to using DECT are provided. Imaging at multiple energy spectra allows for postprocessing of the data and the possibility of creating multiple distinct image reconstructions based on the clinical question being asked. The data regarding utility of DECT in pulmonary vascular disorders, ventilatory defects, and thoracic oncology are presented. A pictorial essay is provided to give examples of the strengths associated with DECT. SUMMARY: DECT has been most heavily studied in chronic thromboembolic pulmonary hypertension; however, it is increasingly being used across a wide spectrum of thoracic diseases. DECT combines morphologic and functional assessments in a single imaging acquisition, providing clinicians with a powerful diagnostic tool. Its role in the evaluation and treatment of thoracic diseases will likely continue to expand in the coming years as clinicians become more experienced with the technology.

Sclerosing epithelioid fibrosarcoma associated with WRN gene variant presenting as chronic dyspnea and pathologic cervical fracture: a case report and review of the literature.

BACKGROUND: Sclerosing epithelioid fibrosarcoma is an aggressive sarcoma subtype with poor prognosis and limited response to conventional chemotherapy regimens. Diagnosis can be difficult owing to its variable presentation, and cases of sclerosing epithelioid fibrosarcoma are rare. Sclerosing epithelioid fibrosarcoma typically affects middle-aged individuals, with studies inconsistently citing gender predominance. Sclerosing epithelioid fibrosarcoma typically arises from the bones and soft tissues and often has local recurrence after resection and late metastases. Immunohistochemical staining typically is positive for mucin-4. Werner syndrome is due to an autosomal recessive mutation in the WRN gene and predisposes patients to malignancy. CASE PRESENTATION: A 37-year-old Caucasian female presented to the emergency department with 4 months of dyspnea and back pain. She had been treated for pneumonia but had persistent symptoms. A chest, abdomen, and pelvis computed tomography showed near-complete right upper lobe collapse and consolidation, mediastinal lymphadenopathy, lytic spinal lesions, and a single 15-mm hypodense liver nodule. The patient underwent a transthoracic right upper lobe biopsy, bronchoscopy, endobronchial ultrasound with transbronchial lymph node sampling, and bronchoalveolar lavage of the right upper lobe. The bronchoalveolar lavage cytology was positive for malignant cells compatible with poorly differentiated non-small cell carcinoma; however, the cell block materials were insufficient to run immunostains for further investigation of the bronchoalveolar lavage results. Consequently, the patient also underwent a liver biopsy of the liver nodule, which later confirmed a diagnosis of sclerosing epithelioid fibrosarcoma. Next-generation sequencing revealed a variant of unknown significance in the WRN gene. She was subsequently started on doxorubicin. CONCLUSION: Sclerosing epithelioid fibrosarcoma is a very rare entity, only cited approximately 100 times in literature to date. Physicians should be aware of this disease entity and consider it in their differential diagnosis. Though pulmonary involvement has been described in the context of sclerosing epithelioid fibrosarcoma, this malignancy may affect many organ systems, warranting extensive investigation. Through our diagnostic workup, we suggest a possible link between sclerosing epithelioid fibrosarcoma and the WRN gene. Further study is needed to advance our understanding of sclerosing epithelioid fibrosarcoma and its clinical associations as it is an exceedingly rare diagnosis.