Chordoma: demographics and survival analysis with a focus on racial disparities and the role of surgery, a U.S. population-based study.

To report two cases of hepatic cavernous hemangioma, a rare complication, in patients with locally advanced and advanced non-squamous non-small cell lung cancer (NSCLC) treated with PD-1 inhibitors. Additionally, to share clinical experiences related to the management of this condition.Two patients with locally advanced and advanced non-squamous non-small cell lung cancer (NSCLC) were enrolled in our hospital. Following the NCCN guidelines and expert consensus, both patients received standard treatment with Camrelizumab (PD-1 inhibitor). Subsequent abdominal CT scans revealed hepatic focal lesions that did not exhibit typical characteristics of metastatic tumors. Therefore, further systematic investigation was conducted to study the hepatic focal lesions.(1) Ultrasound-guided percutaneous biopsy confirmed the diagnosis of hepatic cavernous hemangioma. A multidisciplinary consultation concluded that it was an adverse drug reaction to Camrelizumab. (2) Ten-gene testing for both patients did not reveal any driver gene mutations associated with lung cancer. Apart from the occurrence of hepatic cavernous hemangioma, there were no signs of disease progression or worsening. (3) Both patients had resolution of hepatic cavernous hemangioma after switching to alternative PD-1 inhibitors or discontinuing PD-1 inhibitor treatment. One patient experienced hemorrhage related to the hepatic hemangioma, which was managed with hemostasis and symptomatic treatment, resulting in improvement. (4) Clinical outcomes: The first patient achieved a progression-free survival (PFS) of 33 months in first-line treatment and had not reached the PFS endpoint in second-line treatment, with an overall survival exceeding 56 months. The second patient had not reached the PFS endpoint in first-line treatment, with an overall survival exceeding 31 months.Hepatic cavernous hemangioma is a rare and serious adverse reaction associated with PD-1 inhibitors. Camrelizumab may interact with the PD-1 molecule in a different manner compared to other PD-1 inhibitors, affecting the regulation of the VEGFR/ULBP2 signaling pathway. In future studies, next-generation sequencing may provide detailed molecular pathology information, which could help explain individual differences and provide a basis for the prevention or intervention of hepatic cavernous hemangioma. 

Hepatic cavernous hemangioma developed in non-small cell lung cancer patients after receiving Camrelizumab treatment: two case reports

The treatment metastatic non-small cell lung cancer (NSCLC) is largely influenced by the incorporation of immune checkpoint inhibitors (ICI) in the frontline setting. There are several ICI approved for the management of NSCLC based on the PD-L1 expression of the tumors. PD-L1 is a controversial biomarker with various inconsistencies in expression owing to temporal and spatial heterogeneity. Tumor mutational burden is another much studied biomarker associated with its own challenges and questionable concordance with tumor PD-L1 expression. In this article, we aim to discuss the challenges associated with the existing biomarkers, highlighting the need for emerging biomarkers that can help with decision making in the management of this there where several therapeutic options exist. There are emerging “me too” PD-1/PD-L1 drugs which may serve its purpose in many counties where there is limited access to current approved ICIs. What is increasingly apparent is the need to move the needle forward in the treatment of NSCLC and we will discuss the challenges associated with the current therapeutic landscape and the emerging checkpoints and the future directions that are being explored in the management of metastatic NSCLC.

/pdf/immune-checkpoint-inhibitors-in-metastatic-nsclc-challenges-2nfw9ex0.pdf

Immune checkpoint inhibitors in metastatic NSCLC: challenges and future directions

Small cell lung cancer is an invasive neuroendocrine carcinoma with early metastasis potential. It tends to grow rapidly and metastasize early, with the majority of patients diagnosed as advanced stage small cell lung cancer (ES-SCLC). Systemic treatment consisting of platinum drugs and etoposide chemotherapy is the main treatment method, although the objective effective rate of this combination is 60% - 80%. However, most SCLC patients experience disease progression shortly after initial treatment, with a median overall survival of 10 months. There are few second-line treatment drugs available, and immunotherapy using checkpoint inhibitors has completely changed the treatment of many cancer types. Adding immune checkpoint inhibitors (ICI) to conventional chemotherapy as first-line treatment can improve the survival rate of widespread small cell lung cancer (ES-SCLC), but so far, there are no definitive factors to determine patients who are more likely to benefit from immunotherapy. This review summarizes the results of immunotherapy trials for small cell lung cancer. And a review was conducted on the predictive factors of these trials, with special emphasis on the expression of PD-L1 in small cell lung cancer to determine its clinical value. 

/pdf/a-review-of-the-impact-of-pd-l1-expression-on-the-prognosis-3nbai4l0.pdf

A Review of the Impact of PD-L1 Expression on the Prognosis of Small Cell Lung Cancer

Non-small-cell lung cancer (NSCLC) comprises approximately 85% of all lung cancer cases, often diagnosed at advanced stages, which diminishes the effective treatment options and survival rates. This systematic review assesses the utility of emerging biomarkers—circulating tumor DNA (ctDNA), microRNAs (miRNAs), and the blood tumor mutational burden (bTMB)—enhanced by next-generation sequencing (NGS) to improve the diagnostic accuracy, prognostic evaluation, and treatment strategies in NSCLC. Analyzing data from 37 studies involving 10,332 patients from 2020 to 2024, the review highlights how biomarkers like ctDNA and PD-L1 expression critically inform the selection of personalized therapies, particularly beneficial in the advanced stages of NSCLC. These biomarkers are critical for prognostic assessments and in dynamically adapting treatment plans, where high PD-L1 expression and specific genetic mutations (e.g., ALK fusions, EGFR mutations) significantly guide the use of targeted therapies and immunotherapies. The findings recommend integrating these biomarkers into standardized clinical pathways to maximize their potential in enhancing the treatment precision, ultimately fostering significant advancements in oncology and improving patient outcomes and quality of life. This review substantiates the prognostic and predictive value of these biomarkers and emphasizes the need for ongoing innovation in biomarker research. 

Identification and Application of Emerging Biomarkers in Treatment of Non-Small-Cell Lung Cancer: Systematic Review

Programmed death-ligand (PD-L) 1 and 2 are ligands of programmed cell death 1 (PD-1) receptor. They are members of the B7/CD28 ligand-receptor family and the most investigated inhibitory immune checkpoints at present. PD-L1 is the main effector in PD-1-reliant immunosuppression, as the PD-1/PD-L pathway is a key regulator for T-cell activation. Activation of T-cells warrants the upregulation of PD-1 and production of cytokines which also upregulate PD-L1 expression, creating a positive feedback mechanism that has an important role in the prevention of tissue destruction and development of autoimmunity. In the context of inadequate immune response, the prolonged antigen stimulation leads to chronic PD-1 upregulation and T-cell exhaustion. In lung cancer patients, PD-L1 expression levels have been of special interest since patients with non-small cell lung cancer (NSCLC) demonstrate higher levels of expression and tend to respond more favorably to the evolving PD-1 and PD-L1 inhibitors. The Food and Drug Administration (FDA) has approved the PD-1 inhibitor, pembrolizumab, alone as front-line single-agent therapy instead of chemotherapy in patients with NSCLC and PD-L1 ≥1% expression and chemoimmunotherapy regimens are available for lower stage disease. The National Comprehensive Cancer Network (NCCN) guidelines also delineate treatment by low and high expression of PD-L1 in NSCLC. Thus, studying PD-L1 overexpression levels in the different histological subtypes of lung cancer can affect our approach to treating these patients. There is an evolving role of immunotherapy in the other sub-types of lung cancer, especially small cell lung cancer (SCLC). In addition, within the NSCLC category, squamous cell carcinomas and non-G12C KRAS mutant NSCLC have no specific targetable therapies to date. Therefore, assessment of the PD-L1 expression level among these subtypes of lung cancer is required, since lung cancer is one of the few malignances wherein PD-L1 expression levels is so crucial in determining the role of immunotherapy. In this study, we compared PD-L1 expression in lung cancer according to the histological subtype of the tumor.

/pdf/pd-l1-over-expression-varies-in-different-subtypes-of-lung-3qgo8sm4.pdf

PD-L1 Over-Expression Varies in Different Subtypes of Lung Cancer: Will This Affect Future Therapies?

Chordoma is a rare malignant neoplasm derived from notochordal tissue that primarily affects the axial skeleton. Almost 40% of patients have non-cranial chordoma metastases. The most common metastatic sites are the lungs, bones, lymph nodes, and subcutaneous tissue. We present a 52-year female with a history of sacral chordoma presenting with abdominal fullness, early satiety, and a palpable abdominal mass. Abdominal magnetic resonance imaging (MRI) revealed an isolated, highly vascularized, and multilobed liver mass in the left lateral segment. The mass was surgically removed using a clean surgical margin. A histological examination and immunohistochemical staining were consistent with a metastatic chordoma. Two years later, follow-up imaging studies showed a 6.5 × 4.0 × 2.0 cm right liver lesion with multiple lungs, chest wall, pleural, and diaphragmatic lesions. Microscopic- and immunohistochemical staining revealed a recurrent metastatic chordoma. Herein, we present a unique case of metastatic recurrent chordoma in the liver with the involvement of other sites. To the best of our knowledge, no other case of recurrent liver metastasis has been reported.

https://www.mdpi.com/1718-7729/29/7/367/pdf?version=1656589005

Recurrent Metastatic Chordoma to the Liver: A Case Report and Review of the Literature

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PD-L1 Over-Expression Varies in Different Subtypes of Lung Cancer: Will This Affect Future Therapies?

Recurrent Metastatic Chordoma to the Liver: A Case Report and Review of the Literature