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1.
Cancer Innov ; 3(3): e112, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38947760

ABSTRACT

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive subtype of non-small cell lung cancer (NSCLC), characterized by the presence of epithelial and sarcoma-like components. The molecular and immune landscape of PSC has not been well defined. Methods: Multiomics profiling of 21 pairs of PSCs with matched normal lung tissues was performed through targeted high-depth DNA panel, whole-exome, and RNA sequencing. We describe molecular and immune features that define subgroups of PSC with disparate genomic and immunogenic features as well as distinct clinical outcomes. Results: In total, 27 canonical cancer gene mutations were identified, with TP53 the most frequently mutated gene, followed by KRAS. Interestingly, most TP53 and KRAS mutations were earlier genomic events mapped to the trunks of the tumors, suggesting branching evolution in most PSC tumors. We identified two distinct molecular subtypes of PSC, driven primarily by immune infiltration and signaling. The Immune High (IM-H) subtype was associated with superior survival, highlighting the impact of immune infiltration on the biological and clinical features of localized PSCs. Conclusions: We provided detailed insight into the mutational landscape of PSC and identified two molecular subtypes associated with prognosis. IM-H tumors were associated with favorable recurrence-free survival and overall survival, highlighting the importance of tumor immune infiltration in the biological and clinical features of PSCs.

2.
Transl Oncol ; 47: 101950, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38964032

ABSTRACT

BACKGROUND: Pulmonary sarcomatoid carcinoma (PSC) is a highly invasive pulmonary malignancy with an extremely poor prognosis. The results of previous studies suggest that ubiquitin-specific peptidase 9X (USP9X) contributes to the progression of numerous types of cancer. Nevertheless, there is little knowledge about the molecular mechanisms and functions of USP9X in the metastasis of PSC. METHODS: Immunohistochemistry and western blotting were used to detect USP9X expression levels in PSC tissues and cells. Wound healing, transwell, enzyme-linked immunosorbent assay (ELISA), tube formation, and aortic ring assays were used to examine the function and mechanism of USP9X in the metastasis of PSC. RESULTS: Expression of USP9X was markedly decreased and significantly correlated with metastasis and prognosis of patients with PSC. Then we revealed that USP9X protein levels were negatively associated with the levels of epithelial-mesenchymal transition (EMT) markers and the migration of PSC cells. It was confirmed that USP9X in PSC cells reduced VEGF secretion and inhibited tubule formation of human umbilical vein endothelial cells (HUVEC) in vitro. USP9X was detected to downregulate MMP9. Meanwhile, MMP9 was positively related to EMT, angiogenesis and was negatively related to immune infiltration in the public databases. USP9X was significantly negatively associated with the expression of MMP9, EMT markers, CD31, and positively associated with CD4, and CD8 in PSC tissues. CONCLUSION: The present study reveals the vital role of USP9X in regulating EMT, angiogenesis and immune infiltration and inhibiting metastasis of PSC via downregulating MMP9, which provides a new effective therapeutic target for PSC.

3.
IJU Case Rep ; 7(4): 341-345, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38966777

ABSTRACT

Introduction: The pathologic evaluation and clinical course of cytoreductive nephrectomy after combined immuno-oncology therapy were reviewed to understand the benefits of cytoreductive nephrectomy. Case presentation: Three patients with clear cell carcinoma underwent tumor biopsy before combined immuno-oncology therapy. Case 1 was found to have a sarcomatoid component upon nephrectomy and continued with combined immuno-oncology therapy. Case 2 discontinued combined immuno-oncology therapy due to adverse events but maintained tumor shrinkage. The patient was found to have viable cells in most nephrectomy specimens but has had no recurrence after combined immuno-oncology therapy was discontinued. In case 3, the residual tumor was deemed resectable with combined immuno-oncology therapy, and nephrectomy and metastasectomy were performed. No viable cells were observed in either specimen, and the patient has had no recurrence. Conclusion: Cytoreductive nephrectomy after combined immuno-oncology therapy may be useful to allow pathologic evaluation of treatment and provide an indicator for subsequent treatment.

4.
Transl Lung Cancer Res ; 13(6): 1232-1246, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38973946

ABSTRACT

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare, highly malignant type of non-small cell lung cancer (NSCLC) with a poor prognosis. Targeted drugs for MET exon 14 (METex14) skipping mutation can have considerable clinical benefits. This study aimed to predict METex14 skipping mutation in PSC patients by whole-tumour texture analysis combined with clinical and conventional contrast-enhanced computed tomography (CECT) features. Methods: This retrospective study included 56 patients with PSC diagnosed by pathology. All patients underwent CECT before surgery or other treatment, and both targeted DNA- and RNA-based next-generation sequencing (NGS) were used to detect METex14 skipping mutation status. The patients were divided into two groups: METex14 skipping mutation and nonmutation groups. Overall, 1,316 texture features of the whole tumour were extracted. We also collected 12 clinical and 20 conventional CECT features. After dimensionality reduction and selection, predictive models were established by multivariate logistic regression analysis. Models were evaluated using the area under the curve (AUC), and the clinical utility of the model was assessed by decision curve analysis. Results: METex14 skipping mutation was detected in 17.9% of PSCs. Mutations were found more frequently in those (I) who had smaller long- or short-axis diameters (P=0.02, P=0.01); (II) who had lower T stages (I, II) (P=0.02); and (III) with pseudocapsular or annular enhancement (P=0.03). The combined model based on the conventional and texture models yielded the best performance in predicting METex14 skipping mutation with the highest AUC (0.89). The conventional and texture models also had good performance (AUC =0.83 conventional; =0.88 texture). Conclusions: Whole-tumour texture analysis combined with clinical and conventional CECT features may serve as a noninvasive tool to predict the METex14 skipping mutation status in PSC.

6.
Eur Urol Oncol ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38955577

ABSTRACT

Patients with sarcomatoid renal cell carcinoma (sRCC) have a poor prognosis. In the randomised, double-blind phase 3 IMmotion010 trial (NCT03024996), adjuvant atezolizumab did not demonstrate a disease-free survival (DFS) benefit versus placebo in the overall population of patients with locoregional renal cell carcinoma with an increased risk of recurrence following surgery. This prespecified subgroup analysis of efficacy and safety was completed in 104 patients with sRCC. Baseline characteristics were similar between treatment arms. At a median follow-up of 45 mo, the median DFS was not evaluable (NE; 95% confidence interval [CI], 12 mo-NE) in the atezolizumab arm (n = 37) and 23 mo (95% CI, 11-NE) in the placebo arm (n = 66; hazard ratio 0.77 [95% CI, 0.44-1.4]). In the sRCC subgroup, grade 3/4 treatment-related adverse events (TRAEs) occurred in one patient (2.7%) in the atezolizumab arm and two patients (3.0%) in the placebo arm. By comparison, 54 of 353 patients (15%) and 16 of 317 patients (5.0%) with non-sarcomatoid histology reported grade 3/4 TRAEs in the respective arms. In conclusion, the difference in DFS was not statistically significant between adjuvant atezolizumab and placebo in patients with sRCC. The safety profile was similar between patients with sRCC and non-sRCC. PATIENT SUMMARY: Patients with a specific type of locoregional kidney cancer (tumours with sarcomatoid features) were treated with atezolizumab or placebo after surgery. Slightly more patients treated with atezolizumab lived longer without the disease getting worse than those treated with placebo, although this finding was not statistically significant. The side effects were similar to those seen in patients with other types of kidney cancer treated with atezolizumab in the same study (IMmotion010). In patients with sarcomatoid kidney cancer, atezolizumab was tolerable and may be more effective than placebo, but this requires further study.

7.
Cureus ; 16(6): e61871, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38975456

ABSTRACT

A 76-year-old man who was diagnosed with urothelial carcinoma (UC) in the bladder diverticulum was referred to our institution. The patient was diagnosed with muscle-invasive bladder cancer, which was confirmed by magnetic resonance imaging that showed tumor invasion into the fatty tissue surrounding the diverticulum. After two cycles of neoadjuvant gemcitabine and cisplatin, he underwent robot-assisted radical cystectomy (RARC) with pelvic lymph node dissection followed by intracorporeal ileal conduit. The histopathologic diagnosis of the bladder tumor was UC with squamous differentiation and sarcomatoid subtype and ypT3bN0M0 without positive surgical margins. The patient refused any adjuvant therapy. Six months after RARC, the patient visited our institution with a complaint of suddenly occurring generalized pain. Because 18F-fluorodeoxyglucose positron emission tomography-CT showed multiple metastases, including bone, para-aortic lymph nodes, and pleura, pembrolizumab was initiated as a second-line treatment. After two courses of pembrolizumab, the patient's symptoms remarkably improved, and the abnormal systemic accumulation on PET-CT almost disappeared. After 26 months of continuous treatment with pembrolizumab, the patient remains disease-free. Several studies have been reported that focused on tumor subtypes and programmed cell death ligand 1 (PD-L1)-positive tumor cells as candidate biomarkers in relation to the efficacy of pembrolizumab. The higher proportion of PD-L1-positive cells in the sarcomatoid subtype may have resulted in favorable oncological outcomes compared with pure UC.

8.
Exp Mol Pathol ; 138: 104909, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38876079

ABSTRACT

Epithelial-mesenchymal transition (EMT) plays a pivotal role in the development and progression of many cancers. Partial EMT (pEMT) could represent a critical step in tumor migration and dissemination. Sarcomatoid renal cell carcinoma (sRCC) is an aggressive form of renal cell carcinoma (RCC) composed of a carcinomatous (sRCC-Ca) and sarcomatous (sRCC-Sa) component. The role of (p)EMT in the progression of RCC to sRCC remains unclear. The aim of this study was to investigate the involvement of (p)EMT in RCC and sRCC. Tissue samples from 10 patients with clear cell RCC (ccRCC) and 10 patients with sRCC were selected. The expression of main EMT markers (miR-200 family, miR-205, SNAI1/2, TWIST1/2, ZEB1/2, CDH1/2, VIM) was analyzed by qPCR in ccRCC, sRCC-Ca, and sRCC-Sa and compared to non-neoplastic tissue and between both groups. Expression of E-cadherin, N-cadherin, vimentin and ZEB2 was analyzed using immunohistochemistry. miR-200c was downregulated in sRCC-Ca compared to ccRCC, while miR-200a was downregulated in sRCC-Sa compared to ccRCC. CDH1 was downregulated in sRCC-Sa when compared to any other group. ZEB2 was downregulated in ccRCC and sRCC compared to corresponding non-neoplastic kidney. A positive correlation was observed between CDH1 expression and miR-200a/b/c. Our results suggest that full EMT is not present in sRCC. Instead, discreet molecular differences exist between ccRCC, sRCC-Ca, and sRCC-Sa, possibly representing distinct intermediary states undergoing pEMT.

9.
J Clin Med ; 13(12)2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38929965

ABSTRACT

Germ cell tumor of the testis (GCT) is a curable cancer even when it is widely metastatic; however, outcomes can differ based on tumor histology. Chemo-resistance in certain phenotypes, such as teratoma and yolk sac tumor, contributes to poor clinical outcomes in some patients with GCT. Despite this resistance to S-YSTemic therapy, many of these tumor subtypes remain amenable to surgical resection and possible cure. In this study, we report on a series of seven patients highlighting two chemo-resistant subtypes of nonseminomatous germ cell tumor (NSGCT), sarcomatoid yolk sac tumor (S-YST), and epithelioid trophoblastic tumor (ETT) for which early resection rather than additional salvage chemotherapy or high-dose intense chemotherapy might provide a superior clinical outcome and enhance cure rate.

10.
Asian J Surg ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38834468
11.
Cureus ; 16(5): e59992, 2024 May.
Article in English | MEDLINE | ID: mdl-38854258

ABSTRACT

Carcinosarcoma or sarcomatoid carcinoma of the urinary bladder is a rare but aggressive bladder cancer characterized by malignant epithelial and mesenchymal components, with only a few cases reported in the literature so far. In this report, we discuss a case of a 74-year-old female nonsmoker who presented with intermittent hematuria and passage of clots in the last four months. Radiographic images showed an irregular mass lesion (6.2 x 6 cm) in the left lateral wall of the urinary bladder near to left vesicoureteral junction. The mass was completely removed with transurethral resection of the bladder tumor (TUR-BT). Histopathological study revealed high-grade carcinosarcoma, and immunohistochemistry showed diffuse positivity for vimentin, pan-cytokeratin (CK) and CK7, epithelial membrane antigen (EMA), and CK5/6. The patient declined radical cystectomy and only agreed to receive intravesical chemotherapy (gemcitabine), and she remains alive after more than four years of follow-up. Carcinosarcoma of the urinary bladder is a rare tumor primarily affecting older people, and it is most commonly treated with radical cystectomy and different combination treatments such as chemotherapy and radiation. However, tumor resection followed by intravesical chemotherapy may be an alternative option in the early stages of bladder carcinosarcoma for some patients, thereby avoiding the need for aggressive treatments, especially for elderly patients who decline to undergo radical surgery.

12.
Cell Rep ; 43(6): 114350, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38870013

ABSTRACT

Renal cell carcinoma with sarcomatoid differentiation (sRCC) is associated with poor survival and a heightened response to immune checkpoint inhibitors (ICIs). Two major barriers to improving outcomes for sRCC are the limited understanding of its gene regulatory programs and the low diagnostic yield of tumor biopsies due to spatial heterogeneity. Herein, we characterized the epigenomic landscape of sRCC by profiling 107 epigenomic libraries from tissue and plasma samples from 50 patients with RCC and healthy volunteers. By profiling histone modifications and DNA methylation, we identified highly recurrent epigenomic reprogramming enriched in sRCC. Furthermore, CRISPRa experiments implicated the transcription factor FOSL1 in activating sRCC-associated gene regulatory programs, and FOSL1 expression was associated with the response to ICIs in RCC in two randomized clinical trials. Finally, we established a blood-based diagnostic approach using detectable sRCC epigenomic signatures in patient plasma, providing a framework for discovering epigenomic correlates of tumor histology via liquid biopsy.


Subject(s)
Carcinoma, Renal Cell , Epigenomics , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/metabolism , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Kidney Neoplasms/metabolism , Epigenomics/methods , DNA Methylation/genetics , Cell Differentiation , Gene Expression Regulation, Neoplastic , Male , Female , Epigenesis, Genetic , Middle Aged , Proto-Oncogene Proteins c-fos
13.
Front Oncol ; 14: 1361250, 2024.
Article in English | MEDLINE | ID: mdl-38841172

ABSTRACT

Sarcomatoid renal cell carcinoma (SRCC), a manifestation of sarcomatoid dedifferentiation in renal cell carcinoma, is characterized by elevated invasiveness and a grim prognosis. Typically, SRCC patients present with advanced or metastatic conditions and survival rates rarely extend beyond one year. In this study, we describe a case of SRCC characterized by the patient exhibiting right flank pain without hematuria. Initially, imaging interpretations led to a diagnosis of severe hydronephrosis. Subsequently, an open right nephrectomy post-surgery confirmed the pathology of sarcomatoid renal cell carcinoma.

14.
Mol Med ; 30(1): 73, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38822233

ABSTRACT

Human malignant pleural mesothelioma (hMPM) is an aggressive, rare disease with a poor prognosis. Histologically, MPM is categorized into epithelioid, biphasic, and sarcomatoid subtypes, with the epithelioid subtype generally displaying a better response to treatment. Conversely, effective therapies for the non-epithelioid subtypes are limited. This study aimed to investigate the potential role of FK228, a histone deacetylase inhibitor, in the suppression of hMPM tumor growth. We conducted a comprehensive analysis of the histological and molecular characteristics of two MPM cell lines, CRL-5820 (epithelioid) and CRL-5946 (non-epithelioid). CRL-5946 cells and non-epithelioid patient-derived xenografted mice exhibited heightened growth rates compared to those with epithelioid MPM. Both CRL-5946 cells and non-epithelioid mice displayed a poor response to cisplatin. However, FK228 markedly inhibited the growth of both epithelioid and non-epithelioid tumor cells in vitro and in vivo. Cell cycle analysis revealed FK228-induced G1/S and mitotic arrest in MPM cells. Caspase inhibitor experiments demonstrated that FK228-triggered apoptosis occurred via a caspase-dependent pathway in CRL-5946 but not in CRL-5820 cells. Additionally, a cytokine array analysis showed that FK228 reduced the release of growth factors, including platelet-derived and vascular endothelial growth factors, specifically in CRL-5946 cells. These results indicate that FK228 exhibits therapeutic potential in MPM by inducing cytotoxicity and modulating the tumor microenvironment, potentially benefiting both epithelioid and non-epithelioid subtypes.


Subject(s)
Apoptosis , Cell Proliferation , Depsipeptides , Mesothelioma, Malignant , Mesothelioma , Xenograft Model Antitumor Assays , Humans , Animals , Mesothelioma, Malignant/drug therapy , Mesothelioma, Malignant/pathology , Cell Line, Tumor , Mice , Mesothelioma/drug therapy , Mesothelioma/pathology , Apoptosis/drug effects , Cell Proliferation/drug effects , Depsipeptides/pharmacology , Depsipeptides/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Pleural Neoplasms/drug therapy , Pleural Neoplasms/pathology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Female , Epithelioid Cells/pathology , Cell Cycle/drug effects
15.
Int J Surg Case Rep ; 119: 109675, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38718493

ABSTRACT

INTRODUCTION: Pulmonary sarcomatoid carcinoma is a very rare primary tumor of the lung. Although usually aggressive, these tumors have not been described previously to invade through the diaphragm into the liver. We present a patient with a pulmonary sarcomatoid carcinoma with transdiaphragmatic spread into the dome of the liver. PRESENTATION OF CASE: An 82-year-old female with a lifetime non-smoking history presented with generalized fatigue, fever, night sweats, cough, and pleuritic chest pain. She had recently traveled to the western United States. Additionally, she had recently undergone periodontal deep cleaning with no peri-procedural antibiotics. Laboratory testing was significant for a leukocytosis of 13.5 white blood cells per microliter and a negative viral panel. Computed tomography and magnetic resonance imaging revealed a large heterogeneous mass extending from the right pulmonary hilum through the diaphragm. Although initial radiology reports suggested hepatic abscess, percutaneous fine needle aspiration was performed. Biopsy revealed pulmonary sarcomatoid carcinoma. She was begun on systemic treatment. DISCUSSION: Pulmonary sarcomatoid carcinoma can exhibit transdiaphragmatic invasion into the liver. This clinical situation can easily be confused with a hepatic abscess, but suspicion should remain for abscess. Clinical suspicion for neoplasm should warrant biopsy when technically possible. CONCLUSION: Although hepatic abscesses can exhibit transdiaphragmatic spread into the chest, pulmonary sarcomatoid carcinoma can also invade the abdomen. Biopsy should be performed during the evaluation and workup of the patient.

16.
Ann Surg Oncol ; 31(8): 5457-5464, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38773038

ABSTRACT

BACKGROUND: In contemporary surgically treated patients with localized high-grade (G3 or G4) clear-cell renal cell carcinoma (ccRCC), it is not known whether presence of sarcomatoid dedifferentiation is an independent predictor and/or an effect modifier, when cancer-specific mortality (CSM) represents an endpoint. METHODS: Within the Surveillance, Epidemiology, and End Results database, all surgically treated localized high-grade ccRCC patients treated between 2010 and 2020 were identified. Univariable and multivariable Cox-regression models were used. RESULTS: In 18,853 surgically treated localized high-grade (G3 or G4) ccRCC patients, 5-year CSM-free survival was 87% (62% vs. 88% with vs. without sarcomatoid dedifferentiation, p < 0.001). Presence of sarcomatoid dedifferentiation was an independent predictor of higher CSM (hazard ratio [HR] 1.8, p < 0.001). In univariable survival analyses predicting CSM, presence versus absence of sarcomatoid dedifferentiation in G3 versus G4 yielded the following hazard ratios: HR 1.0 in absent sarcomatoid dedifferentiation in G3; HR 2.7 (p < 0.001) in absent sarcomatoid dedifferentiation in G4; HR 3.9 (p < 0.001) in present sarcomatoid dedifferentiation in G3; HR 5.1 (p < 0.001) in present sarcomatoid dedifferentiation in G4. Finally, in multivariable Cox-regression analyses, the interaction terms defining present versus absent sarcomatoid dedifferentiation in G3 versus G4 represented independent predictors of higher CSM. CONCLUSIONS: In contemporary surgically treated patients with localized high-grade ccRCC, sarcomatoid dedifferentiation is not only an independent multivariable predictor of higher CSM, but also interacts with tumor grade and results in even better ability to predict CSM.


Subject(s)
Carcinoma, Renal Cell , Cell Dedifferentiation , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/surgery , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/mortality , Male , Female , Kidney Neoplasms/surgery , Kidney Neoplasms/pathology , Kidney Neoplasms/mortality , Survival Rate , Aged , Middle Aged , Prognosis , Follow-Up Studies , SEER Program , Nephrectomy/mortality , Neoplasm Grading
17.
Transl Lung Cancer Res ; 13(4): 749-762, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38736497

ABSTRACT

Background: The efficacy of perioperative chemotherapy (PC) in pulmonary sarcomatoid carcinoma (PSC) is controversial. We conducted this study to investigate the effect of different histological subtypes on the efficacy of PC in PSC patients. Methods: Clinicopathological data of 811 PSC patients of different histological subtypes were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier method and log-rank test were used to evaluate the effects of PC on the overall survival (OS) and cancer-specific survival (CSS) in different subtypes of PSC patients. Propensity score matching (PSM) was used to reduce potential confounding effects. Subgroup analyses were conducted to further investigate the efficacy of PC in patients with different characteristics. Results: A total of 210 (25.89%) enrolled PSC patients received PC. PC was not associated with OS or CSS benefit in pleomorphic carcinoma, giant cell carcinoma, or spindle cell carcinoma patients, neither before nor after matching. But survival benefit of PC was observed in carcinosarcoma patients both before (5-year OS: 48.79% vs. 38.75%, P=0.01) and after (5-year OS: 51.29% vs. 17.54%, P=0.003) matching. Subgroup analyses showed that in patients whose tumor larger than 4 cm, PC was still associated with improved survival in carcinosarcoma, but not in the other histological subtypes of PSC. Conclusions: The efficacy of PC varies between different subtypes of PSC. Survival benefit of PC was only observed in carcinosarcoma patients, but not in pleomorphic carcinoma, giant cell carcinoma, or spindle cell carcinoma patients. Histological subtype should be considered when treating PSC patients with PC.

18.
Front Immunol ; 15: 1372279, 2024.
Article in English | MEDLINE | ID: mdl-38756778

ABSTRACT

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small-cell lung cancer (NSCLC), which is resistant to chemotherapy and radiotherapy with a poor prognosis. PSC is highly malignant and is prone to recurrence even after surgery. The programmed death-ligand 1 (PD-L1) tumor cell proportion score (TPS) 5%, TERT and TP53 gene mutations were detected in this patient accompanied by multiple metastatic sites. The anlotinib is a novel multitarget tyrosine kinase inhibitor (TKI) that could be effective for advanced NSCLC and some sarcoma patients. Limited clinical trials and case reports have shown that PSC patients with gene mutations and PD-L1 expression have good responses to multitarget antiangiogenic drug and immune checkpoint inhibitors (ICIs). In this article, we reported a case with metastatic PSC diagnosed by Computed Tomography (CT)-guided needle biopsy treated with immunotherapy combined with antiangiogenic drugs as a neoadjuvant chemotherapy (NACT). PSC is controlled and the patient achieves successfully limb salvage treatment by surgical resection. Therefore, targeted therapy and immunotherapy can provide sufficient surgical opportunities for limb salvage in the treatment of metastatic PSC patients. Case summary: A 69-year-old male diagnosed with malignant bone tumor in the proximal femur was admitted to our hospital in June 2022 with recurrent fever as well as swelling and pain in the left thigh for twenty days. The initial computed tomography (CT) scan of the chest showed a pulmonary cavity (20 mm × 30 mm) and scattered lung masses. Subsequently, he underwent a CT-guided needle biopsy to distinguish the essence of osteolytic bone destruction and soft tissue mass in the left proximal femur which showed metastatic sarcomatoid carcinoma histology. Genetic testing revealed TERT c.-124C mutation (abundance 8.81%), TP53 p.R342 mutation (abundance 11.35%), tumor mutational burden (TMB) 7.09 muts/Mb, microsatellite stability (MSS), and PD-L1 (SP263) TPS 5% were also detected. The patient was tentatively treated with a combination of antiangiogenic drug and PD-1 inhibitor. After one course, the tumor volume significantly reduced in magnetic resonance imaging (MRI) and pathological fracture occurred in the femur after combined treatment. The patient received proximal femoral tumor resection and prosthesis replacement after defervescence. Sequentially sintilimab with anlotinib were administered for over 1 year. Finally, the local tumor was well controlled, and no obvious drug-related adverse reactions were observed. The lesions in the lung remained in partial response (PR) for more than 16 months and complete response (CR) of metastatic tumor in the proximal femur was observed through imaging examinations. Conclusion: This is the first reported case of a metastatic PSC in femur showing a favorable response to the treatment consisting of anlotinib combined with sintilimab. This case suggests that antiangiogenic therapy combined with immunotherapy may benefit patients with metastatic PSC in the preoperative adjuvant therapy for limb salvage.


Subject(s)
Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols , Bone Neoplasms , Indoles , Lung Neoplasms , Neoadjuvant Therapy , Quinolines , Humans , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Bone Neoplasms/secondary , Bone Neoplasms/drug therapy , Bone Neoplasms/therapy , Lung Neoplasms/secondary , Lung Neoplasms/drug therapy , Quinolines/therapeutic use , Quinolines/administration & dosage , Male , Indoles/therapeutic use , Indoles/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/therapy , Aged , Treatment Outcome , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/adverse effects
19.
Surg Case Rep ; 10(1): 134, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38819480

ABSTRACT

BACKGROUND: Curative intent surgery may be indicated for some patients with resectable early stage malignant pleural mesothelioma (MPM). However, sarcomatoid MPM is a highly aggressive subtype for which curative intent surgery is generally not recommended. CASE PRESENTATION: We present the case of a 63-year-old man who presented with dyspnea and chest tightness. Computed tomography revealed pleural thickening and nodular lesions. A pleural biopsy confirmed lymphohistiocytoid MPM (cT1N0M0, stage IA), prompting surgical intervention. The patient underwent left extrapleural pneumonectomy (EPP), and the final diagnosis was sarcomatoid MPM (pT2N0M0, stage IB). Although post-operative chemotherapy was planned, the patient refused additional treatment, because of the introduction of home oxygen therapy, and has remained recurrence-free for 10 years after the surgery. CONCLUSIONS: This case presents a noteworthy instance of achieving long-term recurrence-free survival solely through curative intent surgery for sarcomatoid MPM. It highlights the potential efficacy of surgical intervention in managing this aggressive subtype, offering a glimmer of hope for improved outcomes. Further research is warranted to better define the role of surgery in the treatment of sarcomatoid MPM.

20.
Ther Adv Med Oncol ; 16: 17588359241249041, 2024.
Article in English | MEDLINE | ID: mdl-38716479

ABSTRACT

Pulmonary sarcomatoid carcinoma (PSC), a rare subtype of non-small cell lung cancer, is highly malignant and has a poor prognosis. Treatments for PSC are presently limited. Traditional treatments provide fewer benefits to PSC patients and are associated with early recurrence and metastasis. Surgical intervention is the preferred option for early-stage PSC patients, whereas chemotherapy, radiotherapy, immunotherapy, and other targeted therapies are recommended for advanced PSC patients. Targeted therapy is only effective in a small number of PSC patients. The initial efficacy of immune checkpoint inhibitors has been acceptable in patients with advanced PSC; therefore, much attention on related biomarkers has been sought. This article aimed to review the research progress of PSC immunotherapy and related diagnostic and prognostic biomarkers in recent years.


Advances in immunotherapy for pulmonary sarcomatoid carcinoma Pulmonary sarcomatoid carcinoma (PSC), a rare subtype of non-small cell lung cancer (NSCLC), is highly malignant and has a poor prognosis. Traditional treatments provide fewer benefits to PSC patients and are associated with early recurrence and metastasis. Targeted therapy is only effective in a small number of PSC patients. The initial efficacy of immune checkpoint inhibitors (ICIs) has been acceptable in patients with advanced PSC, therefore, much attention on related biomarkers has been sought. This article aimed to review the research progress of PSC immunotherapy and related diagnostic and prognostic biomarkers in recent years.

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