Machine learning identifies prognostic subtypes of the tumor microenvironment of NSCLC.

The tumor microenvironment (TME) plays a fundamental role in tumorigenesis, tumor progression, and anti-cancer immunity potential of emerging cancer therapeutics. Understanding inter-patient TME heterogeneity, however, remains a challenge to efficient drug development. This article applies recent advances in machine learning (ML) for survival analysis to a retrospective study of NSCLC patients who received definitive surgical resection and immune pathology following surgery. ML methods are compared for their effectiveness in identifying prognostic subtypes. Six survival models, including Cox regression and five survival machine learning methods, were calibrated and applied to predict survival for NSCLC patients based on PD-L1 expression, CD3 expression, and ten baseline patient characteristics. Prognostic subregions of the biomarker space are delineated for each method using synthetic patient data augmentation and compared between models for overall survival concordance. A total of 423 NSCLC patients (46% female; median age [inter quantile range]: 67 [60-73]) treated with definite surgical resection were included in the study. And 219 (52%) patients experienced events during the observation period consisting of a maximum follow-up of 10 years and median follow up 78 months. The random survival forest (RSF) achieved the highest predictive accuracy, with a C-index of 0.84. The resultant biomarker subtypes demonstrate that patients with high PD-L1 expression combined with low CD3 counts experience higher risk of death within five-years of surgical resection.

A Rare Case of Thoracic SMARCA4-Deficient Undifferentiated Tumor With Diffuse Brain Metastasis.

Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a recently described rare and aggressive malignancy characterized by undifferentiated cell morphology and the loss of the Brahma-related gene 1 (BRG1) protein. Its pathogenesis involves mutational loss of SMARCA4 gene expression, which encodes the BRG1 protein that serves as one of the catalytic subunits of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex. This malignancy of the thorax predominantly affects middle-aged male smokers and commonly metastasizes to lymph nodes, bones, adrenal glands, liver, gastrointestinal tract, central nervous system, and kidney. Cases of brain metastasis have been reported but are less common. We report a case of this tumor initially presenting with diffuse brain metastasis in a 55-year-old male with a significant smoking history. We reviewed the current literature on the diagnostic and therapeutic challenges posed by this highly aggressive thoracic tumor.

Differential Lung Ventilation Under the Veno-Arterial Extracorporeal Membrane Oxygenation Assistance in a Patient With a Giant Thoracic Tumor: A Case Report.

Airway compression resulting from thoracic tumors requires evaluation of the possibility of fatal ventilation failure when securing the airway. A woman presenting with a thoracic mass on the right side causing airway compression at the level of tracheal bifurcation required tumor removal to alleviate the compression; however, securing the airway proved challenging. Furthermore, differential lung ventilation was necessary for surgical management. We planned to secure the airway and manage breathing with the assistance of veno-arterial extracorporeal membrane oxygenation (V-A ECMO) through an interdisciplinary conference and proceeded according to the plan. The intended tracheal tube could be placed, differential lung ventilation was initiated, and the ECMO was removed. The surgical procedure was carried out. In patients presenting with airway stenosis, the possibility of difficulty in securing the airway and ventilation should be assessed in advance. Creating a detailed treatment plan before surgery is recommended.

Neuroganglioma in the posterior mediastinum: an incidental discovery.

Ganglioneuroma, a rare benign neuroblastic tumor, typically arises in the posterior mediastinum, but it can be found in the anterior mediastinum and thymus. Predominantly affecting the young, these asymptomatic tumors are often discovered incidentally through imaging. In our reported case, a 44-year-old woman post-hysterectomy with persistent jaundice was diagnosed with a neuroganglioma in the right posterior mediastinum via a computed tomography (CT) scan. Thoracotomy and resection revealed a 10-cm neuroganglioma untangled from mediastinal planes. Post-surgery, chylothorax emerged, which was managed through a 5-day fasting approach. Thoracic neurogangliomas, rare and often asymptomatic, demand meticulous diagnosis, emphasizing imaging and histopathology, with postoperative vigilance for complications.

Familial multiple endocrine neoplasia type 1 with intrathoracic low-grade fibromyxoid sarcoma.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is a hereditary tumor syndrome characterized by endocrine tumors with mainly a parathyroid, pancreatic, or anterior pituitary origin. Low-grade fibromyxoid sarcoma (LGFMS) is a rare low-grade soft tissue tumor. There is one known report of a patient with MEN1 complicated by LGFMS, which is very rare. Our report represents the second documented case, providing valuable insights. CASE PRESENTATION: A 31-year-old man with the chief complaint of a cough underwent chest contrast-enhanced computed tomography, which revealed a giant hypoabsorptive tumor with a maximum diameter of 23 cm in the left thoracic cavity. The patient was diagnosed with MEN1, as he also possessed a pancreatic neuroendocrine tumor and parathyroid tumor, and because his father had been found to have MEN1. To control hypercalcemia, surgery for the parathyroid tumor was initially performed, followed by surgical resection of the giant thoracic tumor for diagnosis and treatment. Histopathological examination findings of the tumor resulted in a diagnosis of LGFMS. CONCLUSION: We experienced a very rare MEN1 with LGFMS. Although endocrine tumors generally occur more frequently in MEN1, non-endocrine tumors such as the present case should also be noted, reinforcing the importance of systemic imaging scrutiny in addition to early diagnosis and long-term follow-up of MEN1 patients.

Thoracic SMARCA4-Deficient Undifferentiated Tumors With Unusual Presentations: A Case Series.

CONTEXT: Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a recently described aggressive neoplasm of young smokers defined by SMARCA4 inactivating mutations and characterized by cells with rhabdoid morphology, high mitotic activity, and abundant necrosis. OBJECTIVE: Describe and compare 3 unusual presentations of SMARCA4-UT in older adults, including one presenting as a metastatic lesion mimicking a primary bone sarcoma. Discuss the molecular characteristics of SMARCA4-UT and their relationship to nonsmall-cell lung carcinomas with SMARCA4. DESIGN: Three patients with SMARCA4-UTs were identified utilizing a natural language search in CoPath. hematoxylin and eosin sections from all patients as well as Papanicolaou-stained slides and Diff-Quik-stained slides for the first patient were examined. A broad range of immunostains, including BRG1/SMARCA4, were evaluated. Molecular testing was performed via next-generation sequencing. RESULTS: The 3 patients were aged 58, 70, and 70 years. All had a significant smoking history. The first patient presented with an iliac bone mass and mediastinal lymphadenopathy, the second with mediastinal adenopathy, and the third with a paratracheal mass. All 3 tumors showed a diffuse proliferation of pleomorphic, rhabdoid cells with high mitotic activity and tumor necrosis. SMARCA4 was lost in all 3 tumors by immunohistochemistry. Molecular testing revealed SMARCA4 alterations in the first 2. CONCLUSIONS: Thoracic SMARCA4-UT should be considered in the differential diagnosis of pleomorphic rhabdoid tumors in older adults with a smoking history. Although most present as lung and/or mediastinal masses, they may occasionally present as a metastasis and mimic an undifferentiated sarcoma, representing a potential diagnostic pitfall.

A Case of Thoracic Epidural Angiolipoma Causing Severe Spinal Cord Compression With Neurologic Manifestations.

A spinal epidural angiolipoma is a rare, benign tumor of adipocytes and blood vessels that accounts only for a small percentage of all spinal axis tumors. We report a case of a 44-year-old male who presented with three months of progressive decreased sensation and strength from about six cm above the umbilicus down to his feet bilaterally. He presented to the emergency room when he could no longer walk. He also had neurogenic urinary retention and likely neurogenic constipation. Physical exam was notable for decreased sensation, decreased strength, and increased patellar reflexes bilaterally. MRI of the thoracic spine showed a posterior epidural mass that spanned from T2 to T3, measuring 1.2 x 1.7 x 4.3 cm, and severely compressed the spinal cord posteriorly. The patient underwent an urgent laminectomy for decompression and mass resection. Pathology was consistent with an angiolipoma. Postoperatively, he experienced a drastic improvement in strength and gross motor skills. The sensation had a partial return following surgery and continued to improve over the hospital stay. In general, the literature reports significant symptomatic improvement in patients with spinal epidural angiolipomas after surgical resection.

Pseudoprogression of thoracic tumor after radiotherapy in the era of immunotherapy: a case series.

Pseudoprogression is rarely mentioned after radiotherapy except for central nervous system tumors. With the widespread of immunotherapy, the incidence of pseudoprogression of thoracic tumor after radiotherapy is increasing. This study summarized the clinical features of pseudoprogression in 4 patients who had underwent thoracic radiotherapy after and/or followed by immunotherapy. All of them had received chemotherapy and immunotherapy before thoracic radiotherapy. After radiotherapy, pseudoprogression occurred within 3 months after initiation of immune consolidation/rechallenge therapy. At least a 20% increase in the sum of the longest diameter of target lesions were measured on their chest image. During this period, patients' ECOG PS scores remained stable, specific serum tumor markers did not increase significantly. Treatment strategies did not change after pseudoprogression. The causes of radiographic pseudoprogression in this case series may be attributed to disturbances such as pneumonitis, atelectasis, mucus blockages and infection. In the era of immunotherapy, pseudoprogression of thoracic tumors after chest radiotherapy might become a common phenomenon. It is important for us to identify pseudoprogression based on patient's general status, radiological changes, and laboratory tests.

A Subset of Thoracic SMARCA4-Deficient Undifferentiated Tumors Express GATA3.

Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a rare and highly aggressive malignant neoplasm characterized by high-grade undifferentiated morphologic features and recurrent inactivating mutations of SMARCA4. These tumors consistently exhibit loss of SMARCA4 (BRG1) while displaying variable expression of other nonspecific markers. Recently, we encountered a SMARCA4-UT demonstrating immunoreactivity for GATA3, and we sought to characterize this phenomenon in a larger series.A total of nine SMARCA4-UTs were examined from 3 large academic institutions. The clinicopathologic and molecular characteristics were studied and GATA3 immunohistochemistry was performed.The cohort included 5 male and 4 female patients, with a median age of 54 years and a median smoking history of 37 pack-years. At initial diagnosis, mediastinal lymph node involvement was observed in 5 patients (56%) while distant metastases were present in 7 patients (78%). The median survival was 6 months. Histologically, the tumors were characterized by sheets of undifferentiated epithelioid and/or rhabdoid cells, accompanied by frequent mitotic figures and necrosis. Immunohistochemically, all tumors displayed a complete loss of BRG1 expression. Notably, 4 of 9 tumors (44%) were positive for GATA3 expression, including one tumor that exhibited strong and diffuse immunoreactivity.GATA3 expression in SMARCA4-UT may pose diagnostic challenges, requiring differentiation from other GATA3-positive tumors. This distinction is crucial for accurate prognostication and treatment decisions.

Impact of thoracic tumor radiotherapy on survival in non-small-cell lung cancer with malignant pleural effusion treated with targeted therapy: Propensity score matching study.

BACKGROUND: EGFR-mutant (EGFR-M) and ALK-positive (ALK-P)are common in malignant pleural effusion (MPE) with metastatic non-small-cell lung cancer (NSCLC) (MPE-NSCLC). The impact of thoracic tumor radiotherapy on survival in such patients remains unclear. We aimed to investigate whether thoracic tumor radiotherapy could improve overall survival (OS) in such patients. METHODS: According to whether or not patients accepted thoracic tumor radiotherapy, 148 patients with EGFR-M or ALK-P MPE-NSCLC treated with targeted therapy were classified into two groups: DT group without thoracic tumor radiotherapy and DRT group with thoracic tumor radiotherapy. Propensity score matching (PSM) was performed to balance clinical baseline characteristics. Overall survival was analyzed by Kaplan-Meier, compared by log-rank test, and evaluated using Cox proportional hazards model. RESULTS: Median survival time (MST) was 25 months versus 17 months in the DRT group and DT group. The OS rates at 1, 2, 3, 5 years in the DRT group and DT group were 75.0%, 52.8%, 26.8%, 11.1% and 64.5%, 28.4%, 9.2%, 1.8%, respectively (χ2 = 12.028, p = 0.001). Compared with DT group, the DRT group still had better survival after PSM (p = 0.007). Before and after PSM, factors associated with better OS through multivariable analysis were that thoracic tumor radiotherapy, radiotherapy, N0-2 , and ALK-TKIs. Grades 4-5 radiation toxicities were not observed in patients; 8 (11.6%) and 7 (10.1%) out of the DRT group suffered from Grade 3 radiation esophagitis and radiation pneumonitis, respectively. CONCLUSION: Our results for EGFR-M or ALK-P MPE-NSCLC showed that thoracic tumor radiotherapy may be crucial factor in improving OS with acceptable toxicities. Potential biases should not be neglected: Further randomized controlled trials are necessary to confirm this result.

Effectiveness of tislelizumab when combined with etoposide and carboplatin in patients with SMARCA4-deficient undifferentiated thoracic tumor: a case report.

Background: SMARCA4-deficient undifferentiated thoracic tumor (SMARCA4-UT) is a rare malignant condition with high invasiveness and poor prognosis. Presently, no clear guidelines are available for the treatment of SMARCA4-UT. The median overall survival was only four to seven months. Several patients are diagnosed in advanced stages of the malignancy and do not respond to conventional radiotherapy and chemotherapy. Case Description: A 51-year-old Chinese man was diagnosed with a SMARCA4-UT. The patient did not have a chronic history of hypertension or diabetes and any family history of malignant tumors. No sensitive mutation in lung cancer-related ten genes was identified. The first-line therapy with four cycles of liposomal paclitaxel and cisplatin combined with two cycles of tyrosine kinase inhibitor anlotinib failed. On immunohistochemical analysis, no programmed cell death 1 ligand 1 (PD-L1) expression was found. However, whole-exon sequencing revealed a high tumor mutation burden (TMB) of 15.95 mutations/Mb with TP53 and KEAP1 mutations. The patient was treated with a second-line regimen containing tislelizumab, etoposide, and carboplatin (TEC). A reduction in tumor burden was seen for more than 10 months. Conclusions: The case of SMARCA4-UT with a high mutation burden successfully responded to the combined regimen containing TEC. This could be a new treatment option for patients with SMARCA4-UTs.

Thoracic Fetiform Teratoma: A Case Report of a Very Rare Entity in a Peruvian Hospital.

Mature fetiform teratoma, or homunculus, is a term coined for a rare variant of teratoma with a prevalence of 0.01% of teratomas. There have been very few cases reported in the world, and its thoracic presentation is extremely unusual. We present the case of a 31-year-old female patient with a history of progressive chest pain in the left hemithorax, associated with dyspnea on moderate exertion and cough. Imaging studies revealed a large intrathoracic tumor visually compatible with a teratoma. Surgical resection by a clamshell approach was successful, and subsequent anatomopathological studies of the operative specimen concluded that the mass was a mature fetiform thoracic teratoma. The treatment of this entity is generally surgical and includes wide resection due to its large adhesive component to surrounding tissues. Thus, the cardiothoracic surgeon must know approaches that allow wide resection, making these cases true surgical challenges.

Thymic lipofibroadenomas: Three case reports.

BACKGROUND: Thymic lipofibroadenomas are extremely rare. In this study, we investigated the clinicopathological characteristics of thymic lipofibroadenomas. CASE SUMMARY: This study included three patients with thymic lipofibroadenomas. We retrospectively analyzed the patient data to determine the clinicopathological characteristics of thymic lipofibroadenomas. The study included one man and two women [mean age, 43 (33-59) years]. All patients were non-smokers and presented with well-defined anterior mediastinal tumors. The cut surfaces of the tumors were solid, with a mixture of yellow and white areas. Microscopic evaluation of resected specimens showed scattered cord-like structures of epithelial cells embedded within abundant fibrotic and hyaline stroma admixed with variable quantities of adipose tissue. One patient showed hyperplastic thymic tissue in a part of the tumor. CONCLUSION: Thymic lipofibroadenomas are an extremely rare type of benign thymic tumor. Surgical removal of lipofibroadenomas is usually curative.

[Radiation-Induced Heart Disease: Current Status and Challenges].

Being one of the major therapeutic measures for malignant tumors, radiation therapy, or radiotherapy, plays a particularly crucial role in the multidisciplinary integrated treatment of thoracic tumors. With the development in radiotherapy technology, the research focus has shifted from improving the overall survival of malignant tumor patients to reducing the incidence of radiation-related injuries. Currently, radiation-induced heart disease (RIHD) has become one of the leading non-cancer causes of death in thoracic tumor patients who have undergone radiotherapy, seriously affecting their quality of life and clinical prognosis. In recent years, there has been growing understanding of the pathogenesis of RIHD, and proposals have been made for some potential measures for the prevention and treatment of RIHD. Based on the clinical manifestations and pathological changes of RIHD that have been reported, we herein reviewed the biological mechanism and potential treatment options for RIHD. We also discussed existing challenges in the prevention and treatment of RIHD, intending to provide references for the prevention and treatment of RIHD.

Case Report: Primary Thoracic Low-Grade Fibromyxoid Sarcoma in a Young Girl Presenting With Mediastinal Mass Syndrome.

Low-grade fibromyxoid sarcomas (LGFMSs) are typically adult-onset tumors that arise from the extremities. Here, we report an exceptional case of primary thoracic LGFMS in an 8-year-old girl that resulted in mediastinal syndrome. In reporting this case, we discuss the clinical challenges, role of molecular profiling and review reported cases of pediatric thoracic LGFMSs.

Near-Infrared Photoimmunotherapy for Thoracic Cancers: A Translational Perspective.

The conventional treatment of thoracic tumors includes surgery, anticancer drugs, radiation, and cancer immunotherapy. Light therapy for thoracic tumors has long been used as an alternative; conventional light therapy also called photodynamic therapy (PDT) has been used mainly for early-stage lung cancer. Recently, near-infrared photoimmunotherapy (NIR-PIT), which is a completely different concept from conventional PDT, has been developed and approved in Japan for the treatment of recurrent and previously treated head and neck cancer because of its specificity and effectiveness. NIR-PIT can apply to any target by changing to different antigens. In recent years, it has become clear that various specific and promising targets are highly expressed in thoracic tumors. In combination with these various specific targets, NIR-PIT is expected to be an ideal therapeutic approach for thoracic tumors. Additionally, techniques are being developed to further develop NIR-PIT for clinical practice. In this review, NIR-PIT is introduced, and its potential therapeutic applications for thoracic cancers are described.

Liver herniation mimicking a thoracic tumor with restoration of the liver surface structure on closure of the hernia orifice under thoracoscopic surgery.

Non-congenital, non-traumatic spontaneous diaphragmatic liver hernia in adults is extremely rare and sometimes misdiagnosed as a thoracic tumor. Almost all previous reports with a definitive diagnosis reported preservation; thus, differential diagnosis is extremely important for planning optimal management of such clinical conditions. An abnormal shadow in the right lower lung field was detected on chest radiography in a 61-year-old woman. Further imaging study revealed a 33-mm diameter mass adjacent to the right diaphragm. Thoracoscopic surgery was performed as diagnostic treatment. We found a pale hemispherical herniated liver on the central tendon of the diaphragm. After repositioning the herniated liver, the orifice was closed with a non-absorbable suture, and the surface of the liver returned to being a perfectly smooth surface. With this result, we believe that repair of diaphragmatic liver hernia through a minimally invasive procedure has great benefits for patients.

Sulfated Glycans Recognized by S1 Monoclonal Antibody can Serve as a Diagnostic Marker for Malignant Pleural Mesothelioma.

PURPOSE: Malignant pleural mesothelioma (MPM) is a malignant neoplasm of the pleura caused by asbestos exposure. For diagnosis of MPM, immunohistochemistry using multiple markers is recommended to rule out differential diagnoses, such as pulmonary adenocarcinoma. However, the specificity of currently used markers is not fully satisfactory. We previously developed a monoclonal antibody named S1, which recognizes 6-sulfo sialyl Lewis x, an L-selectin ligand expressed on high endothelial venules. During the screening process, we discovered that this antibody stained normal pleural mesothelium. This finding prompted us to hypothesize that the epitope recognized by S1 might serve as a new diagnostic marker for MPM. METHODS: To test this hypothesis, we immunostained human MPM (n = 22) and lung adenocarcinoma (n = 25) tissues using S1 antibody. RESULTS: 77.3% of MPM were S1 positive, and if limited to epithelioid type, the positivity rate was 100%, while that of lung adenocarcinoma was only 36.0%. Statistical analysis revealed a significant difference in the S1 positivity rate between each disease. Furthermore, immunohistochemistry using a series of anti-carbohydrate antibodies combined with glycosidase digestion revealed the structure of sulfated glycans expressed in MPM to be 6-sulfo sialyl N-acetyllactosamine attached to core 2-branched O-glycans. CONCLUSION: We propose that the S1 glycoepitope could serve as a new diagnostic marker for MPM.

Analysis on the accuracy of CT-guided radioactive I-125 seed implantation with 3D printing template assistance in the treatment of thoracic malignant tumors.

This article analyzes the accuracy of needle track and dose of a 3-dimensional printing template (3DPT) in the treatment of thoracic tumor with radioactive I-125 seed implantation (RISI). A total of 28 patients were included. The technical process included: (i) preoperative CT positioning, (ii) preoperative planning design, (iii) 3DPT design and printing, (iv) 3DPT alignment, (v) puncture and seed implantation. The errors of needle position and dosimetric parameters were analyzed. A total of 318 needles were used. The mean errors in needle depth, needle insertion point, needle tip and needle angle were 0.52 ± 0.48 cm, 3.4 ± 1.7 mm, 4.4 ± 2.9 mm and 2.8 ± 1.7°, respectively. The differences between actual needle insertion angle and needle depth and those designed in the preoperative were statistically significant (p < 0.05). The mean values of all the errors of the chest wall cases were smaller than those of the lungs, and the differences were statistically significant (p < 0.05). There was no significant difference between the D90 calculated in the postoperative plan and those designed in the preoperative and intraoperative plans (p > 0.05). Some dosimetric parameters of preoperative plans such as V100, V200, CI and HI were not consistent with that of preoperative plans, and the difference was statistically significant (p < 0.05). However, there were no statistical difference in the dosimetric parameters between the postoperative plans and intraoperative plans (p > 0.05). We conclude that for thoracic tumors, even under the guidance of 3DPT, there will be errors. The plan should be optimized in real time during the operation.

Thoracic Sertoli-Leydig cell tumor: An alternative type of pleuropulmonary blastoma associated with DICER1 variation.

A 2-year-old boy presented with a large cystic and solid chest mass arising from the lung, radiographically consistent with pleuropulmonary blastoma (PPB). He underwent right lower lobectomy with resection of a well-circumscribed, mixed solid and cystic mass. The solid areas were composed of cords and nests of tumor cells in the myxoid stroma and retiform foci whose pathologic and immunophenotypic findings were consistent with a sex cord-stromal tumor with features of a Sertoli-Leydig cell tumor. Tumor testing showed a pathogenic variant in the DICER1 RNase IIIb hotspot domain. Family history was suggestive of DICER1 germline pathogenic DICER1 variation in absence of a detectable germline variant. He received 12 cycles of chemotherapy with ifosfamide, vincristine, dactinomycin and doxorubicin (IVADo) and surgery with complete response. One year after completion of chemotherapy, imaging studies showed concern for recurrence confirmed by thorascopic biopsy of a pleural-based mass. He is currently receiving cisplatin-based chemotherapy with reduction in tumor size. Review of the literature showed no similar cases; however, review of our pathology files revealed a single similar case of anterior mediastinal Sertoli cell tumor in a 3-year-old girl.