Advanced Nonmelanoma Skin Cancer Research Articles

Efficacy and Safety of Cemiplimab for the Management of Non-Melanoma Skin Cancer: A Drug Safety Evaluation.

Non-melanoma skin cancer includes several types of cutaneous tumors, with basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) as the commonest. Among the available therapeutic options, surgical excision is the mainstay of treatment for both tumors. However, tumor features and patients' comorbidities may limit the use of these techniques, making the treatment challenging. As regards BCC, even if hedgehog inhibitors revolutionized the therapeutic scenario, there are still patients unresponsive or intolerant to these drugs. In this context, cemiplimab has been approved as second-line treatment. As regards SCC, cemiplimab was the first systemic therapy approved. The objective of this manuscript was to investigate the efficacy and safety of cemiplimab for the management of BCC and cSCC. Cemiplimab has a durable and significant effect for the management of BCC and CSCC, with a favorable safety profile. Different specialists including oncologists, radiologists, dermatologists, and surgeons are required to guarantee an integrated approach, leading to the best management of patients. Moreover, the collaboration among specialists will allow them to best manage the TEAEs, reducing the risk of treatment suspension or discontinuation. Certainly, ongoing studies and more and more emerging real-world evidence, will allow us to better characterize the role of cemiplimab for the management of advanced non-melanoma skin cancer.

Combination of Upfront Systemic Therapy and Radiation in Advanced Non-Melanoma Skin Cancer

Combination of Upfront Systemic Therapy and Radiation in Advanced Non-Melanoma Skin Cancer

Craniectomy with soft tissue reconstruction for locally advanced non-melanoma skin cancer of scalp with calvarial invasion: The Nottingham experience

IntroductionLocally advanced non-melanoma skin cancer (NMSC) involving the periosteum or calvarium poses a clinical challenge for patients who are unfit for immunotherapy due to medical comorbidities and/or frailty. This case series aims to investigate outcomes for patients undergoing craniectomy and soft tissue reconstruction. MethodPatients who underwent craniectomy and soft tissue reconstruction for invasive NMSC with calvarium or periosteal invasion between 2016 and 2022 were included. Data, including demographics, operative details, and clinical outcomes, were gathered from Nottingham University Hospitals’ digital health record and the histopathology electronic database. ResultEight patients (average age: 78.4 years, 3 females 5 males) with significant comorbidities and varying degrees of periosteal or bone invasion fulfilled the inclusion criteria. Diagnoses included four squamous cell carcinomas, two basal cell carcinomas, and two pleomorphic dermal sarcomas. Five patients had a history of prior incomplete deep margin excision. The median sizes for soft tissue defect, tumor and bone defect size were 51.83 cm2, 34.63 cm2 and 42.25 cm2, respectively. Intraoperative complications included one dural tear. Four patients underwent local flap reconstruction and with split-thickness skin grafting, four patients underwent free flap reconstruction. Adjuvant radiotherapy was administered to three patients. Complications comprised partial graft loss in two and complete graft loss in one. There was partial flap loss in one case. One patient required subsequent parotidectomy due to regional progression before achieving disease control. All patients achieved lasting locoregional disease control (average follow-up 29.7 months). ConclusionCraniectomy with soft tissue reconstruction proves to be a safe and effective treatment option in advanced NMSC of the scalp in patients unsuitable for immunotherapy due to frailty or medical co-morbidity.

Non-Surgical Therapeutic Strategies for Non-Melanoma Skin Cancers.

Non-melanoma skin cancer (NMSC) is a globally prevalent skin disease, with basal cell carcinoma and squamous cell carcinoma accounting for 99% of NMSC cases. While surgical excision is the most common approach, numerous non-surgical therapies have rapidly advanced in recent years. In cases of low-risk NMSC, alongside surgical excision, priority should be given to physical therapy and photodynamic therapy. Physical therapy modalities, exemplified by electrodessication and curettage, emerge as safe and efficacious alternatives. In juxtaposition, photodynamic therapy, albeit relatively more costly, assumes preference for patients exhibiting heightened cosmetic concerns owing to the scarring risks inherent to physical therapy and surgical excision. Notably, the combination of curettage and photodynamic therapy has exhibited remarkable efficacy in the treatment of nodular basal cell carcinoma. Additionally, for elderly patients who may be intolerant to stimulation, modified photodynamic therapy offers an almost painless option. When surgery is unavoidable, photodynamic therapy can be a valuable adjunct, allowing for a more conservative surgical approach, either before or after the procedure. Radiotherapy holds a prominent role in comprehensive treatment strategies, especially for patients ineligible for surgical intervention or those with lesions precluding further surgical measures. In cases of NMSC exhibiting perineural invasion or lymphovascular involvement, adjunctive radiotherapy is advised; however, potential adverse effects necessitate careful consideration. For advanced NMSC cases where surgery and physical therapy fall short, immunotherapy provide viable solutions. Systemic therapy employing Hedgehog pathway inhibitors can be considered for patients with distant metastatic basal cell carcinoma, despite its low incidence, or individuals with locally advanced lesions who are not surgical candidates, or those encountering recurrences after resection and radiotherapy. However, close monitoring of disease progression and adverse reactions is crucial. In this evolving landscape of NMSC treatment, personalized and multidisciplinary approaches are key, ensuring optimal outcomes while prioritizing patient safety and satisfaction.

Advanced Non-Melanoma Skin Cancers: Effective Practices in Multidisciplinary Care: Leveraging Multidisciplinary Networks to Improve Care

Advanced Non-Melanoma Skin Cancers: Effective Practices in Multidisciplinary Care: Leveraging Multidisciplinary Networks to Improve Care

Surgery in the Era of Immunotherapy for Advanced Head and Neck Non-melanoma Skin Cancer.

Surgery remains the mainstay of treatment for non-melanoma skin cancer (NMSC). Immunotherapy (IO) has emerged as an alternative option. This review provides a contemporary summary of how to incorporate IO into the management of advanced NMSC. Evidence-based outcomes and recent clinical trials are provided with emphasis on the three most common NMSC diagnoses: cutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC), and merkel cell carcinoma (MCC). Surgical resection while preserving form and function remains the standard of care for the majority of NMSCs. In recalcitrant cases failing traditional surgery and/or primary radiation, patient ineligible for such treatments, or unresectable disease, IO has emerged as a promising alternative. In the majority of cases, it is a supplanting primary chemotherapy. Surgery remains the standard of care for NMSC. Immunotherapy has emerged as an alternative option for non-surgical candidates and as a neoadjuvant means to minimize morbidity.

Management of Non-Melanoma Skin Cancer: Radiologists Challenging and Risk Assessment.

Basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma are the three main types of nonmelanoma skin cancers and their rates of occurrence and mortality have been steadily rising over the past few decades. For radiologists, it is still difficult to treat patients with advanced nonmelanoma skin cancer. Nonmelanoma skin cancer patients would benefit greatly from an improved diagnostic imaging-based risk stratification and staging method that takes into account patient characteristics. The risk is especially elevated among those who previously received systemic treatment or phototherapy. Systemic treatments, including biologic therapies and methotrexate (MTX), are effective in managing immune-mediated diseases; however, they may increase susceptibility to NMSC due to immunosuppression or other factors. Risk stratification and staging tools are crucial in treatment planning and prognostic evaluation. PET/CT appears more sensitive and superior to CT and MRI for nodal and distant metastasis as well as in surveillance after surgery. The patient treatment response improved with advent and utilization of immunotherapy and different immune-specific criteria are established to standardized evaluation criteria of clinical trials but none of them have been utilized routinely with immunotherapy. The advent of immunotherapy has also arisen new critical issues for radiologists, such as atypical response pattern, pseudo-progression, as well as immune-related adverse events that require early identification to optimize and improve patient prognosis and management. It is important for radiologists to have knowledge of the radiologic features site of the tumor, clinical stage, histological subtype, and any high-risk features to assess immunotherapy treatment response and immune-related adverse events.

Advanced non-melanoma skin cancer in elderly patients: When surgery says NO, interventional radiotherapy (brachytherapy) says YES.

The prevalence of non-melanoma skin cancer (NMSC) increases, especially in older adults with comorbidities, narrowing radical treatment options. About 5% of skin cancer patients are diagnosed with an advanced stage, which impairs daily functioning. The study was to present a retrospective summary of elderly patients unfit for surgery and treated with various brachytherapy (BT) techniques tailored individually for locally advanced NMSCs in a reference BT department. Clinical case presentations supported the findings. Inoperable patients older than 75 years presenting with advanced pathologically confirmed NMSCs were retrospectively identified. All cases were individually assessed, and the best suiting radical treatment option was chosen, including contact, interstitial, or hybrid high-dose-rate (HDR) or pulsed-dose-rate (PDR) BT. Doses ranging from 45 to 60 Gy were administered to clinical target volume (CTV) in different time schedules. All patients were closely followed-up until complete remission. Ten elderly patients (mean age, 84 years) with differently located locally advanced NMSCs (all staged T3) were treated between 2007 and 2022. Six basal and four squamous cell carcinoma cases showed most painful symptoms as well as bleeding and exudation. Six patients underwent HDR-BT and four PDR-BT. Six patients had superficial, and four interstitial or hybrid applications. All patients completed the intended protocols. Median follow-up was 8.5 months (range, 3-35 months). Six out of ten patients died from other reasons before analysis. All case data were presented in the text and respective figures. Advanced NMSCs in elderly patients are challenging in terms of cure. Inoperable cases may be referred for feasible and locally effective interventional radiotherapy (BT). Individually tailored BT leads to an excellent disease control, function sparing, symptoms release, and quality of life improvement. Large treated volumes are related to prolonged healing. BT should be discussed in a multidisciplinary tumor board regarding older patients with symptomatic functions affecting advanced NMSCs.

QUAD SHOT - an effective hypofractionated palliative radiotherapy in patients with non-melanoma skin cancer. A single-institution experience.

The primary approach for managing skin cancer involves surgery, although radical radiotherapy (RT) may be considered as an alternative option in cases where patients decline the treatment themselves or are not eligible for surgical intervention. Herein we assess single-institution material in terms of the use of hypofractionated QUAD SHOT RT in patients disqualified from surgery. Between December 2019 and December 2022, nine patients with locally advanced non-melanoma skin cancer were disqualified from surgery and as a result were treated at the Radom Oncology Centre, Poland. Patients were treated with the Radiation Therapy Oncology Group 8502 QUAD SHOT regimen (14.8 Gy/4 fractions, twice-daily treatment with a 6 h interval, on 2 consecutive days). Courses were repeated every 4 weeks 3 times using volumetric modulated arc therapy (VMAT). Grade 2 toxicities were observed in 4 of 9 (44.4%) patients, no grade ≥ 3 acute toxicity was observed. The median age was 79.1 (60-98) years. Irradiated areas were as follows: nose skin (2), cheek (2), eyebrow with eyelid (1), forehead (1), temple (1), sternum (1), and scapula (1). Performance status was as follows: WHO II - 5 patients (55.6%), WHO I - 3 patients, WHO III - one patient. One patient underwent 3 RT courses in 2 areas for a total of 6 treatment courses, 6 patients received 3 courses of treatment, and 2 patients received 2 courses. Additionally, as of 14 March 2023, four patients died of non-malignant causes. QUAD SHOT schedule with VMAT RT may be an effective palliative treatment method with a good response rate, which positively affects patients' quality of life in locally advanced non-melanoma skin cancer patients disqualified from surgery.

Áttörés az előrehaladott és metasztatikus hámeredetű bőrdaganatok kezelésében

Non-melanoma skin cancers (NMSCs) are the most common malignant tumors worldwide and their incidence shows a continuous increase. Basal cell-, and squamous cell carcinoma account for approximately 99% of the NMSC cases. The majority of NMSCs are curable, however, there are locally advanced or distant metastatic cases where our therapeutic options have been limited until nowadays. In this article, the authors briefly summarize the registered systemic therapies used in the treatment of advanced NMSCs, as well as provide an outlook on possible future therapies.

Review of sociodemographic risk factors for presentation with advanced non-melanoma skin cancer

ABSTRACT Purpose Non-melanoma skin cancers (NMSC) are often localized and associated with an excellent prognosis but a minority present with locally advanced or metastatic disease requiring extensive resection or systemic treatment. Medical factors that increase the risk of advanced skin cancers such as tobacco use, systemic immunosuppression or genetic syndromes have been described but the sociodemographic risk factors are relatively uninvestigated and under reported. In this review a cohort of patients presenting with periorbital NMSC is reviewed for social determinants of health correlated with presentation with advanced disease. Methods Patients presenting with periorbital NMSC during a 10-year period are categorized as advanced (those tumors requiring extensive local resection, sacrifice of the globe or systemic therapy) or non-advanced and demographic features are compared between the two groups. Results 274 cases of periorbital NMSC were classified as either non-advanced (177) or advanced (97). Patients with public safety net health insurance were twice as likely to present with advanced disease (25% vs 13%). Patients with advanced disease were significantly less likely to be under the care of a primary care physician, lived in economically depressed areas with lower mean household incomes, and lived further from tertiary medical care. Conclusion Financial and sociodemographic features are strongly associated with presentation with advanced NMSC. Further work is needed to determine which sociodemographic features are independent risk factors. A better understanding of the relevant barriers to care may reduce the burden of advanced disease at presentation in the future.

Beyond Immunotherapy: Seizing the Momentum of Oncolytic Viruses in the Ideal Platform of Skin Cancers.

Simple SummaryOncolytic viruses (OVs) are the most innovative and promising class of intratumoral immunotherapies. The broad immunogenic landscape of skin cancer, accessible to intralesional infusion and available for direct response assessment, seems to be an ideal platform to expand the role of OVs. The established efficacy of immune checkpoint inhibitors (ICIs) in this field and their hypothetical synergy with OVs have generated expectations for their combined use beyond the current immunotherapy achievements. Despite the recent negative phase III results of the MASTERKEY-265 trial for the combination of T-VEC plus pembrolizumab, such projects, including different ICIs and various natural or genetically modified OVs, continue to attract considerable interest, with numerous clinical trials underway for all the subtypes of skin cancer. To date, the majority of studies confirm the safety of tested OVs in patients with advanced skin cancers but cannot clearly prove whether these viral agents add any therapeutic benefit in the standard ICI-based approach. The aim of this overview is to present the main findings related to the examined OV-containing regimens at pre-clinical and clinical levels, and to discuss the previous failures as well as the future perspectives of oncolytic virotherapy.Despite the durable remissions induced by ICIs and targeted therapies in advanced melanoma and non-melanoma skin cancers, both subtypes usually relapse. Many systematic therapies have been tested to increase efficacy and delay relapse in ICIs, but their success has been limited. Due the feasibility of this approach, skin cancers have become the ideal platform for intralesional infusions of many novel agents, including oncolytic viruses (OVs). Talimogene laherparepvec (T-VEC) was the first FDA-approved OV for the treatment of unresectable melanoma and this virus opened up further potential for the use of this class of agents, especially in combination with ICIs, in order to achieve deeper and longer immune-mediated responses. However, the recently announced phase III MASTERKEY-265 trial was not able to confirm that the addition of T-VEC to pembrolizumab treatment improves progression-free or overall survival over the use of pembrolizumab alone. Despite these results, numerous studies are currently active, evaluating T-VEC and several other OVs as monotherapies or in regimens with ICIs in different subtypes of skin cancer. This overview provides a comprehensive update on the evolution status of all available OVs in melanoma and non-melanoma skin cancers and summarizes the more interesting preclinical findings, the latest clinical evidence, and the future insights in relation to the expected selective incorporation of some of these OVs into oncological practice.

Macrophage and T-Cell Infiltration and Topographic Immune Cell Distribution in Non-Melanoma Skin Cancer of the Head and Neck.

Non-melanoma skin cancer (NMSC) is a heterogeneous tumor entity that is vastly determined by age and UV-light exposure leading to a great mutational burden in cancer cells. However, the success of immune checkpoint blockade in advanced NMSC and the incidence and disease control rates of NMSC in organ transplant recipients compared to immunologically uncompromised patients point toward the emerging importance of the immunologic activity of NMSC. To gain first insight into the role of T-cell and macrophage infiltration in NMSC of the head and neck and capture their different immunogenic profiles, which appear to be highly relevant for the response to immunotherapy, we conducted a whole slide analysis of 107 basal cell carcinoma (BCC) samples and 117 cutaneous squamous cell carcinoma (cSCC) samples. The CD8+ and CD68+ immune cell expression in both cancer types was evaluated by immunohistochemistry and a topographic distribution profile, and the proportion of both cell populations within the two tumor entities was assessed. The results show highly significant differences in terms of CD8+ T-cell and CD68+ macrophage infiltration in BCC and cSCC and indicate cSCC as a highly immunogenic tumor. Yet, BCC presents less immune cell infiltration; the relation between the immune cells compared to cSCC does not show any significant difference. These findings help explain disparities in local aggressiveness, distant metastasis, and eligibility for immune checkpoint blockade in both tumor entities and encourage further research.

Immune Checkpoint Inhibition in Non-Melanoma Skin Cancer: A Review of Current Evidence.

Immuno-oncology is a rapidly evolving field with growing relevance in the treatment of numerous malignancies. The prior study of immunotherapy in dermatologic oncology has largely focused on cutaneous melanoma. However, recent focus has shifted to the use of immunotherapy to treat non-melanoma skin cancers (NMSCs), such as basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and Merkel cell carcinoma (MCC). NMSCs represent the most ubiquitous cancers globally and, while they have a lower propensity to develop into advanced disease than cutaneous melanoma, their absolute mortality burden has recently surpassed that of melanoma. Patients with advanced NMSC are now benefiting from the successes of immunotherapy, including checkpoint inhibition with anti-CTLA-4 and anti-PD-1 monoclonal antibodies. In this review, we discuss the existing clinical evidence for immunotherapy in the treatment of NMSCs, with an emphasis on checkpoint inhibitor therapies. We highlight key studies in the field and provide up-to-date clinical evidence regarding ongoing clinical trials, as well as future study directions. Our review demonstrates that checkpoint inhibitors are positioned to provide unparalleled results in the previously challenging landscape of advanced NMSC treatment.

Locally Advanced Scalp Tumors: Clinical and Survival Outcomes of a Tertiary Unit.

Locally advanced nonmelanoma skin cancers of the head and neck are well described in the current literature. However, data about clinical and survival outcomes are lacking. We present survival data from a tertiary head and neck cancer unit in London. A retrospective analysis of data collected from a single institution was conducted. All patients with locally advanced cutaneous scalp carcinomas invading the skull between 2011 and 2019 were included. Data included patient demographics, tumor, comorbidities, interventions, flap survival, and metal work exposure. Survival outcomes were examined using Kaplan-Meier analysis. Twenty-three patients were identified. The mean age was 72 years. Eighteen patients were male, and 5 were female. Five patients were immunosuppressed. Nineteen patients underwent outer cortex drill-down/full-thickness calvarial resection, followed by reconstruction with free tissue transfer. Six patients had titanium mesh reconstruction after segmental skull resections. Three patients underwent further surgery because of exposed metalwork. Disease-free survival at 3 years after surgery was 60%. Locally advanced nonmelanoma skin cancers invading the bone are sporadic. There are little published data on clinical and survival outcomes in this group. Despite the nature of these skin lesions, a high degree of local control can be obtained by extensive surgical resection, outer table drill-down, and calvarial resection. We conclude that aggressive management of the bony invasion improves disease-free survival and improves local control.

Immunotherapy for Non-melanoma Skin Cancer

Purpose of ReviewThe therapeutic landscape for non-melanoma skin cancer (NMSC) has recently expanded with the development of effective and targeted immunotherapy. Here, we provide an overview of the role of immunotherapy in the management of advanced cutaneous carcinomas.Recent FindingsSeveral agents were recently U.S. Food and Drug Administration (FDA)-approved for the treatment of locally advanced and metastatic cutaneous squamous cell carcinoma, Merkel cell carcinoma, and basal cell carcinoma. However, recent approvals in tissue-agnostic indications may also benefit other NMSCs including cutaneous adnexal solid tumors with high tumor mutation burdens or microsatellite instability. Furthermore, while FDA-approved indications will likely continue to expand, continued studies are needed to support the role of immunotherapy in the neoadjuvant, adjuvant, and refractory settings.SummaryImmunotherapy is emerging as the standard of care for several advanced NMSCs not amenable to surgery and radiation. Ongoing evaluation of the clinical trial landscape is needed to optimize enrollment and ensure continued innovation.

25686 Variability in the dosing of PD1 inhibitors used for treatment of nonmelanoma skin cancers

Nonmelanoma skin cancer (NMSC) represents the most common cancer diagnosed in the United States. These tumors are frequently treated by surgical modalities. Patients with advanced disease require a different approach to therapy. Programmed cell death protein 1 (PD1) inhibitors are an emerging immunotherapeutic option for the treatment of a variety of tumors including advanced NMSC. Cemiplimab is a PD-1 inhibitor approved for treatment of locally advanced or metastatic cutaneous squamous cell carcinoma (cSCC) not amenable to curative surgery or radiation. Pembrolizumab and nivolumab are PD1 inhibitors used as off-label therapies for advanced cSCC or basal cell carcinoma (BCC). We conducted a PubMed literature search up to August 8, 2020 to include studies on the use of PD-1 inhibitors in patients with advanced NMSC. Thirty-seven articles reported a total of 432 unique cases of advanced cSCC or BCC treated with PD1 inhibitors. The most common dosing schedules for pembrolizumab (2 mg/kg q3 weeks), nivolumab (3 mg/kg q2 weeks), or cemiplimab (3 mg/kg q2 weeks) were identified. A total of 10 different dosing schedules were identified. Outcomes of these patients ranged between progressive disease to achievement of a complete clinical response. All 3 PD1 inhibitors showed adequate safety profiles with few reported adverse events that were grade 3 or above. The use of cemiplimab, pembrolizumab, and nivolumab for advanced NMSC has shown promising results. However, the literature shows a wide range of dosing regimens for these therapies. Further studies are needed to guide clinicians toward the optimal dosage and the ideal anti-PD1 agent for their patients.

Comprehensive management of nonmelanoma skin cancer involving the skull base.

Skin cancers are the most prevalent malignant disorder affecting humans. Approximately 90% of these are nonmelanoma skin cancer (NMSC), and large tumors, especially at the 'H-zone', can invade deeply and access the skull base. The best treatment for these very advanced skin cancers is craniofacial resection followed by adjuvant treatment, but, currently, systemic therapy and neoadjuvant approaches could be considered for some patients. The current management of NMSC involving the skull base is discussed in this article. Surgical resections with negative margins followed by adjuvant treatment are the best treatment for NMSC with skull base invasion and offer the best outcomes for those patients. This approach usually requires a free flap reconstruction, followed by external beam radiation therapy. The team must keep in mind that some factors, such as gross brain invasion and extensive dura mater extension, are associated with worse outcomes. Although it occurs infrequently, very advanced NMSC can involve the skull base. In these very difficult clinical scenarios, the best therapeutic option is a multidisciplinary approach in a tertiary center.

Investigative Landscape in Advanced Non-Melanoma Skin Cancers.

Advanced non-melanoma skin cancers have been challenging to treat due to limited treatment options. Treatment paradigm has shifted with the approval of immunotherapeutic agents cemiplimab and pembrolizumab which have been a key development and have changed the landscape of advanced or metastatic squamous cell skin cancers. Hedgehog inhibitors, vismodegib and sonidegib, remain upfront options for advanced or metastatic basal cell carcinomas. Current clinical trials are continuing to evaluate the use of immune checkpoint inhibitors and hedgehog pathway inhibitors. There is further need for ongoing research and development of new therapies in both malignancies.

Histopathologic PD-L1 Tumor Expression and Prognostic Significance in Nonmelanoma Skin Cancers: A Systematic Review.

PD-L1 and PD-1 inhibitors are being increasingly used to treat a variety of nonmelanoma skin cancers (NMSCs). This systematic review summarizes PD-L1 expression in NMSCs and determines its use for prognosis using targeted immunotherapy. A primary search of peer-reviewed English-language medical literature was conducted for studies on PD-L1 tumor expression in biopsied or excised NMSCs. Fifty-nine articles met criteria for inclusion. PD-L1 expression in advanced NMSCs ranged from 22%-89% for basal cell carcinomas, 42%-50% for Merkel cell carcinomas, and 26%-100% for squamous cell carcinomas. Study limitations included clone heterogeneity across studies, complicating comparison of PD-L1 expression. Differences were also noted in the selection of tumor reactivity threshold. We conclude that there is insufficient evidence to determine the prognostic significance of PD-L1 expression in NMSCs as a whole, but this remains a promising area. More investigation into the role of tumor PD-L1 as a biomarker for predicting clinical response to PD-L1 and PD-1 inhibitors in NMSCs is needed.