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RELATED :BCC (Basal Cell Carcinoma):SCC (Squamous Cell Carcinoma)

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HD-MT With/Without IT-MT and WBRT for Primary CNS Lymphoma

KEY TAKEAWAYS The study aimed to evaluate the efficacy and safety of HD-MT with or without IT-MT and WBRT for PCNSL. The results showed no significant difference in efficacy between HD-MT alone or with IT-MT plus radiotherapy, with manageable side effects. Primary...

Sep 19, 2024

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Jet-Injected ALA PDT: Effective for Nodular BCC

KEY TAKEAWAYS

  • The phase II pilot study aimed to assess the safety and efficacy of JI-PDT in treating pts with BCC.
  • The results revealed that the Jet-injected ALA-PDT shows promise as a viable treatment option.

Photodynamic therapy (PDT) using δ-Aminolevulinic acid (ALA) topically demonstrated effectiveness in basal cell carcinoma (BCC) treatment but faced challenges due to inadequate penetration of ALA into deeper skin layers.

In this pilot trial, Leore Lavin and the team aimed to assess the safety and efficacy of photosensitizer jet injection (JI-PDT) for treating BCC. This open-label prospective study enrolled 15 patients (pts) with histologically confirmed, untreated, low-risk nodular BCCs.

Researchers noted that the intervention, JI-PDT pts (n = 11) received 2 sessions of jet-injected ALA with PDT separated by four to 6 weeks. Another group of pts (n = 4) underwent jet-injected ALA followed by tumor excision and fluorescence microscopy (JI-E). Treatment tolerability was assessed by local skin responses (LSR) score at 5 distinct time intervals.

Fluorescence microscopy evaluated protoporphyrin IX penetration depth and biodistribution within the tumor. At the primary endpoint, tumor clearance was evaluated via visual inspection, dermoscopy, and reflectance confocal microscopy. Postinjection and postillumination pain levels, and pts satisfaction, were scored on a 0-10 scale.

Results revealed that 15 participants, with a mean age of 58.3 years and all non-Hispanic White, enrolled in the study. The median composite LSR score immediately after JI-PDT was 5 (IQR = 3), decreasing significantly to 0.5 (IQR = 1) at the primary endpoint (P < 0.01). Immunofluorescence analysis of excised BCC tumors treated with jet-injected ALA revealed effective photosensitizer penetration into both papillary and reticular dermis.

Among the 13 tumors treated with JI-PDT, 11 achieved confirmed tumor clearance, while 1 recurred and 1 was lost to follow-up. 1 patient experienced a serious adverse event of cellulitis. At 3 months, 70% of pts exhibited local scarring. Pts reported an average pain level of 5.6 (SD = 2.3) during jet injection and 3.7 (SD = 1.8) during light illumination.

In conclusion, the JI of ALA for PDT in nodular low-risk BCC is viable and tolerable, which can prospectively offer a promising treatment approach.

The trial was sponsored by Memorial Sloan Kettering Cancer Center and the study was financially supported by LEO Pharma and P30 CA008748/NH/NIH HHS/United States.

Source: https://pubmed.ncbi.nlm.nih.gov/38804170/

Clinical Trial: https://www.clinicaltrials.gov/study/NCT04552990

Lavin L., Erlendsson A.M., Aleissa S., et al. (2024). “Jet-injection assisted photodynamic therapy for superficial and nodular basal cell carcinoma: A pilot study.” Lasers Surg Med. 2024 Jul;56(5):446-453. doi: 10.1002/lsm.23793. Epub 2024 May 28. PMID: 38804170.

Prognostic Role of SOX2 and KLF4 in Oral SCC

KEY TAKEAWAYS

  • The study aimed to investigate the significance of basal differentiation in patients with oral SCC as a prognostic indicator.
  • Researchers noticed that Basal differentiation and SOX2/KLF4 expression in basal layers are key prognostic factors for oral SCC.

Basal differentiation in oral squamous cell carcinoma (SCC) is typically identified at invasive sites, yet its prognostic value remains underexplored.

Kazuhiro Murakami and the team aimed to investigate the significance of basal differentiation as a prognostic indicator in oral SCC.

They performed an inclusive analysis by subclassifying 65 cases of oral SCC into COL17-high (30 cases) and -low (35 cases) types. Prognostic value was assessed using Cox regression analysis. Additionally, immunohistochemical analysis included stem cell markers such as SOX2, KLF4, MYC, and stem cell-related markers BMI1, EZH2, YAP, and TAZ, investigating their prognostic significance in relation to COL17 status.

About disease-specific survival and recurrence-free survival (RFS) in oral SCC, no significant difference was observed between the COL17-high and -low groups. Combining the COL17-high and -low categories with SOX2, KLF4, EZH2, or YAP/TAZ status in basal layers, alongside gender and age as covariates, resulted in hazard ratios of 3.3, 3.7, 2.8, and 3.1, respectively. Multivariate analysis, including COL17, SOX2, and KLF4, with gender and age as covariates, indicated a significantly poorer prognosis for disease-specific survival.

The study concluded that basal differentiation and the expression status of SOX2 and KLF4 in basal layers are significant prognostic factors for oral SCC, as indicated by their relatively high hazard ratios.

No funding information was given.

Source: https://pubmed.ncbi.nlm.nih.gov/38659289/

Murakami K, Kamiakito T, Kawata H, et al. (2024). “Basal differentiation and expression status of SOX2 and KLF4 in basal layers are prognostic factors for disease-specific survival in oral squamous cell carcinoma.” J Oral Pathol Med. 2024 May;53(5):303-309. doi: 10.1111/jop.13535. Epub 2024 Apr 24. PMID: 38659289.

Predicting LACSC Recurrence with SCC

KEY TAKEAWAYS

  • The study aimed to investigate the clinical significance of serum SCC antigen levels in patients with LACSC.
  • Researchers noticed a strong correlation between serum SCC antigen levels and recurrence sites in patients with LACSC.

Although serum squamous cell carcinoma (SCC) antigen values are known to be useful in predicting the prognosis of cervical SCC, they have only been examined in a cursory manner.

Yusuke Yamaoka and the team aimed to meticulously investigate the clinical significance of serum SCC antigen levels in patients with locally advanced cervical squamous cell carcinoma (LACSC).

They performed an inclusive analysis involving patients diagnosed with the local stage (T-stage) 1b3/2/3 LACSC who underwent initial treatment at the institute between January 2006 and December 2016 (T-1b3: n=30; T-2: n=75; T-3: n=34). Patients were categorized into three groups based on pre-treatment SCC values, and differences in clinical background, laboratory and pathology findings, and prognosis were examined.

About the SCC distribution, no significant difference was observed among the T-1b3/2/3 cases with elevated SCC levels. In stages T-1b3, T-2, and T-3, most recurrences in the SCC-High group were distant (T-1b3: 3 out of 5 recurrences; T-2: 6 out of 7 recurrences; T-3: 4 out of 8 recurrences), while most recurrences in the SCC-Low group were pelvic (T-1b3: 2 out of 3 recurrences; T-2: 8 out of 8 recurrences; T-3: 3 out of 3 recurrences).

The study concluded that in LACSC, serum SCC antigen levels before treatment strongly correlate with the recurrence site. Patients with low levels should be closely monitored for local recurrence, while those with high levels warrant vigilance for distant recurrence.

No funding information was given.

Source: https://pubmed.ncbi.nlm.nih.gov/38677756/

Yamaoka Y, Tamura S, Yamanoi K, et al. (2024). “Clinical Significance of Serum SCC Levels Before Treatment for Locally Advanced Cervical Squamous Cell Carcinoma.” Anticancer Res. 2024 May;44(5):2009-2019. doi: 10.21873/anticanres.17004. PMID: 38677756.

Prognostic Role of SOX2 and KLF4 in Oral SCC

Prognostic Role of SOX2 and KLF4 in Oral SCC

KEY TAKEAWAYS

  • The study aimed to investigate the significance of basal differentiation in patients with oral SCC as a prognostic indicator.
  • Researchers noticed that Basal differentiation and SOX2/KLF4 expression in basal layers are key prognostic factors for oral SCC.

Basal differentiation in oral squamous cell carcinoma (SCC) is typically identified at invasive sites, yet its prognostic value remains underexplored.

Kazuhiro Murakami and the team aimed to investigate the significance of basal differentiation as a prognostic indicator in oral SCC.

They performed an inclusive analysis by subclassifying 65 cases of oral SCC into COL17-high (30 cases) and -low (35 cases) types. Prognostic value was assessed using Cox regression analysis. Additionally, immunohistochemical analysis included stem cell markers such as SOX2, KLF4, MYC, and stem cell-related markers BMI1, EZH2, YAP, and TAZ, investigating their prognostic significance in relation to COL17 status.

About disease-specific survival and recurrence-free survival (RFS) in oral SCC, no significant difference was observed between the COL17-high and -low groups. Combining the COL17-high and -low categories with SOX2, KLF4, EZH2, or YAP/TAZ status in basal layers, alongside gender and age as covariates, resulted in hazard ratios of 3.3, 3.7, 2.8, and 3.1, respectively. Multivariate analysis, including COL17, SOX2, and KLF4, with gender and age as covariates, indicated a significantly poorer prognosis for disease-specific survival.

The study concluded that basal differentiation and the expression status of SOX2 and KLF4 in basal layers are significant prognostic factors for oral SCC, as indicated by their relatively high hazard ratios.

No funding information was given.

Source: https://pubmed.ncbi.nlm.nih.gov/38659289/

Murakami K, Kamiakito T, Kawata H, et al. (2024). “Basal differentiation and expression status of SOX2 and KLF4 in basal layers are prognostic factors for disease-specific survival in oral squamous cell carcinoma.” J Oral Pathol Med. 2024 May;53(5):303-309. doi: 10.1111/jop.13535. Epub 2024 Apr 24. PMID: 38659289.

Heme Metabolism Regulates Phagocytosis in UEC via TLR4/CD36

KEY TAKEAWAYS

  • The study aimed to investigate how active heme metabolism suppresses macrophage phagocytosis in UEC via the TLR4/IFN pathway.
  • Researchers concluded that active heme metabolism in UEC inhibits macrophage phagocytosis, aiding immune escape.

Uterine endometrial cancer (UEC) is a common gynecological estrogen-dependent carcinoma, often associated with intermenstrual bleeding. Active heme metabolism is increasingly recognized for its significant role in various diseases, particularly cancers.

Tumor-associated macrophages (TAMs) constitute the predominant immune cells within the microenvironment of UEC, yet the influence of heme metabolism on the interaction between UEC cells (UECCs) and macrophages remains poorly understood.

Xing Zhang and the team aimed to assess the impact of active heme metabolism on the crosstalk between UECCs and TAMs, specifically examining its effect on suppressing macrophage phagocytosis through the TLR4/IFN signaling pathway and CD36 expression.

Researchers performed an inclusive analysis utilizing the TCGA database and conducted an integration analysis of the protein-protein interaction (PPI) network, alongside RNA transcriptome sequencing of patient samples.

The expression levels of both heme-associated molecules and iron metabolism-related molecules were measured using quantitative real-time polymerase chain reaction. Heme levels were detected through a dehydrohorseradish peroxidase assay.

Additionally, immunohistochemistry, phagocytosis assays of macrophages, immunofluorescence staining, intracellular ferrous iron staining, and enzyme-linked immunosorbent assays were conducted to further explore the interactions and effects within the tumor microenvironment.

About the results, it was verified that heme accumulation in UECCs is significantly higher compared to endometrial epithelium cells. Low expression of succinate dehydrogenase B, regulated by estrogen, contributes to the overproduction of succinate and subsequent heme accumulation in UECCs.

More importantly, excessive heme in UECCs impairs macrophage phagocytosis through the regulation of CD36. Mechanistically, this impairment is dependent on the toll-like receptor (TLR4)/type I interferons alpha (IFN Iα) regulatory axis in macrophages.

The study concluded that active heme metabolism in UECCs directly diminishes macrophage phagocytosis by regulating the secretion of TLR4-mediated IFN Iα and the expression of CD36, thereby promoting immune escape in UEC.

This study was funded by the National Key Research and Development Program of China, the Program of National Natural Science Foundation of China, the Shanghai Natural Science Foundation, and the Shanghai Oriental Talent Plan.

Source: https://pubmed.ncbi.nlm.nih.gov/39166450/

Zhang X, Yang YX, Lu JJ, et al. (2024). “Active Heme Metabolism Suppresses Macrophage Phagocytosis via the TLR4/Type I IFN Signaling/CD36 in Uterine Endometrial Cancer.” Am J Reprod Immunol. 2024 Aug;92(2):e13916. doi: 10.1111/aji.13916. PMID: 39166450.

Role of AXL in SCC Development Among Patients With CLL

KEY TAKEAWAYS

  • The study aimed to investigate the role of AXL activation in the progression of SCC in early-stage, untreated patients with CLL.
  • Researchers found that AXL drives SCC in CLL, suggesting AXL inhibition as a potential therapy.

Occurrence of squamous cell carcinoma (SCC), even in patients with early-stage, untreated chronic lymphocytic leukemia (CLL), presents a significant morbidity risk, with instances of transformation into metastatic skin lesions.

Sutapa Sinha and the team aimed to investigate the underlying mechanisms contributing to SCC development in patients with CLL, focusing on the potential role of AXL signaling in driving cancer progression.

They performed an inclusive analysis involving the purification of CLL cells and extracellular vesicles (EVs) from the blood/plasma of patients with CLL. The expression and activation of AXL were assessed, focusing on its functions in normal keratinocytes (HEKa) using an in vitro co-culture system. Additionally, AXL activity was evaluated in SCC tissues to understand its role in the progression of squamous cell carcinoma in patients with CLL.

About the results, researchers detected aberrant activation of AXL, AKT, and ERK-1/2 in SCC cell lines compared to HEKa. They also observed increased expression of AXL in primary SCC tissues obtained from patients with CLL. Increased activation of AXL, AKT, ERK-1/2, and Src was discernible in HEKa upon co-culturing with CLL cells.

Further analysis suggests that Gas6, a ligand of AXL, regulates AXL activation in co-cultured HEKa. Interestingly, exposure of HEKa cells to CLL plasma-derived EVs induced the expression of AXL, P-AKT, and EMT-associated markers, leading to cell migration. Finally, pharmacologic inhibition of AXL-induced cell death in SCC lines in a dose-dependent manner.

The study concluded that CLL cells are likely involved in driving SCC progression, at least in part, via activation of the AXL signaling axis. This indicates that AXL inhibition may be beneficial for CLL patients with SCC.

This study was funded by Mayo Internal Funding.

Source: https://pubmed.ncbi.nlm.nih.gov/38886556/

Sinha S, Guo R, Del Busso MD, et al. (2024). “Aberrant activation of AXL may drive progression of squamous cell carcinoma in CLL patients: a mechanistic study with clinical implications.” Br J Cancer. 2024 Aug;131(3):589-600. doi: 10.1038/s41416-024-02752-1. Epub 2024 Jun 17. PMID: 38886556; PMCID: PMC11300914.

Impact of Cemiplimab on QoL in Patients With mBCC

KEY TAKEAWAYS

  • The phase 2 trial aimed to assess the impact of cemiplimab on QoL in patients with mBCC unsuitable for HHI.
  • Researchers noticed that cemiplimab treatment in patients with mBCC led to improved or maintained GHS.

A phase 2 cemiplimab study (NCT03132636) demonstrated a 24.1% objective response rate (ORR) in patients diagnosed with metastatic basal cell carcinoma (mBCC) who were not candidates for continued hedgehog inhibitor (HHI) therapy due to intolerance to previous HHI therapy, disease progression while receiving HHI therapy, or having not better than stable disease on HHI therapy after 9 months. This abstract reports on the health-related quality of life (QoL) for this patient population.

Ketty Peris and the team aimed to assess the impact of cemiplimab treatment on health-related QoL in these patients.

They performed an inclusive analysis of adult patients with mBCC treated with intravenous cemiplimab at a dose of 350 mg every 3 weeks for 5 treatment cycles of 9 weeks each, followed by 4 treatment cycles of 12 weeks each.

Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (QLQ-C30) and Skindex-16 questionnaires at baseline and on Day 1 of each cycle. Across Cycles 2 to 9, the overall change from baseline was analyzed using a mixed model with repeated measures. Responder analyses determined clinically meaningful improvement or deterioration (changes ≥10 points) or maintenance across all scales.

About patients reported low symptom burden and moderate-to-high functioning at baseline. Maintenance for QLQ-C30 global health status (GHS)/QoL and across all functioning and symptom scales was indicated by overall mean changes from baseline.

Clinically meaningful improvement or maintenance was reported at Cycle 2 for GHS/QoL (77%), functioning scales (77% to 86%), and symptom scales (70% to 93%), with similar proportions of improvement or maintenance at Cycles 6 and 9, excluding fatigue.

On the Skindex-16, clinically meaningful improvement or maintenance was reported across the emotional, symptom, and functional subscales, in 76%-88% of patients at Cycle 2, which were generally maintained at Cycles 6 and 9. Overall mean changes from baseline showed maintenance across these subscales.

The study concluded that the majority of patients treated with cemiplimab reported improvement or maintenance in GHS/QoL and functioning while maintaining a low symptom burden.

Funding support was provided by Regeneron Pharmaceuticals, Inc., and Sanofi.

Source: https://pubmed.ncbi.nlm.nih.gov/39031963/

Clinical Trial: https://clinicaltrials.gov/study/NCT03132636

Peris K, Inocencio TJ, Stratigos AJ, et al. (2024). “Health-related quality of life in patients with metastatic basal cell carcinoma treated with cemiplimab: Analysis of a phase 2 trial.” Cancer Med. 2024 Jul;13(14):e7360. doi: 10.1002/cam4.7360. PMID: 39031963; PMCID: PMC11259569.

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