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1.
Saudi Med J ; 45(5): 481-489, 2024 May.
Article in English | MEDLINE | ID: mdl-38734428

ABSTRACT

OBJECTIVES: To assess the clinical relevance and prognostic value of changes in the Naples prognostic score (NPS) after neoadjuvant chemoradiotherapy (NACR) among esophageal squamous cell carcinoma (ESCC) patients. METHODS: We studied 232 locally advanced ESCC patients who received NACR before undergoing esophagectomy retrospectively. Categorizing individuals into the elevated NPS group and the non-elevated NPS group based on the change in NPS after NACR (ΔNPS > 0 or ∆NPS ≤ 0), we examined and compared the clinicopathological characteristics, survival rates, and postoperative complications between these 2 groups (∆NPS = post-NACR NPS - pre-NACR NPS). RESULTS: Results: Out of the 232 patients enrolled, 105 exhibited elevated NPS levels, while 127 showed non-elevated NPS levels. Survival analyses indicated inferior overall survival (OS) (p=0.024) and recurrence-free survival (RFS) (p=0.047) in the elevated NPS cohort compared to the non-elevated NPS cohort. Subsequent cox regression analyses identified the post-NACR change in NPS as an independent prognostic indicator for RFS (p=0.029) and OS (p=0.036). CONCLUSION: Elevated NPS post-NACR emerged as a significant indicator of worse prognosis for locally advanced ESCC patients who underwent NACR. This finding has great potential to be useful for recognizing high-risk ESCC patients who received NACR before undergoing esophagectomy and making individualized subsequent therapeutic decisions in clinical practice.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Esophagectomy , Neoadjuvant Therapy , Humans , Female , Esophageal Neoplasms/therapy , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Male , Middle Aged , Prognosis , Esophageal Squamous Cell Carcinoma/therapy , Esophageal Squamous Cell Carcinoma/mortality , Esophageal Squamous Cell Carcinoma/pathology , Retrospective Studies , Aged , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Survival Rate , Chemoradiotherapy/methods , Disease-Free Survival
2.
BMC Cancer ; 24(1): 585, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38741038

ABSTRACT

OBJECTIVE: The optimal timing for surgery following neoadjuvant immunochemotherapy for lung squamous cell carcinoma appears to be a topic of limited data. Many clinical studies lack stringent guidelines regarding this timing. The objective of this study is to explore the effect of the interval between neoadjuvant immunochemotherapy and surgery on survival outcomes in patients with lung squamous cell carcinoma. METHODS: This study conducted a retrospective analysis of patients with lung squamous cell carcinoma who underwent neoadjuvant immunochemotherapy between January 2019 and October 2022 at The First Affiliated Hospital, Zhejiang University School of Medicine. Patients were divided into two groups based on the treatment interval: ≤33 days and > 33 days. The primary observational endpoints of the study were Disease-Free Survival (DFS) and Overall Survival (OS). Secondary observational endpoints included Objective response rate (ORR), Major Pathological Response (MPR), and Pathological Complete Remission (pCR). RESULTS: Using the Kaplan-Meier methods, the ≤ 33d group demonstrated a superior DFS curve compared to the > 33d group (p = 0.0015). The median DFS for the two groups was 952 days and 590 days, respectively. There was no statistical difference in the OS curves between the groups (p = 0.66), and the median OS was not reached for either group. The treatment interval did not influence the pathologic response of the tumor or lymph nodes. CONCLUSIONS: The study observed that shorter treatment intervals were associated with improved DFS, without influencing OS, pathologic response, or surgical safety. Patients should avoid having a prolonged treatment interval between neoadjuvant immunochemotherapy and surgery.


Subject(s)
Carcinoma, Squamous Cell , Lung Neoplasms , Neoadjuvant Therapy , Humans , Male , Neoadjuvant Therapy/methods , Female , Lung Neoplasms/therapy , Lung Neoplasms/mortality , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Middle Aged , Retrospective Studies , Aged , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Disease-Free Survival , Pneumonectomy , Time-to-Treatment , Adult , Treatment Outcome
3.
Cancer Immunol Immunother ; 73(7): 118, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38713217

ABSTRACT

BACKGROUND: In a princeps study we conducted in patients with advanced cutaneous squamous cell carcinoma treated with concomitant anti-Programmed cell death protein 1 (PD-1) and radiotherapy, we demonstrated a clinico radiological response to cemiplimab that appeared to persist over time, 1 year after treatment discontinuation. METHOD: We conducted a single-center descriptive study at Caen Hospital from September 1, 2021 to September 2023, in 14 patients with advanced carcinoma treated with cemiplimab until September 1, 2021. The aim of this update is to examine clinical and radiological follow-up 2 years after discontinuation of cemiplimab. RESULTS: Of the 12 patients with a partial or complete response, we report 8 (66.7%) persistent responses 2 years after stopping cemiplimab, with only 2 patients progressing to distant disease, one lost to follow-up, and one death a priori unrelated to the disease. CONCLUSION: Our study confirms a long-term and persistent effect despite discontinuation of cemiplimab at least up to 2 years later.


Subject(s)
Antibodies, Monoclonal, Humanized , Carcinoma, Squamous Cell , Skin Neoplasms , Humans , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Skin Neoplasms/drug therapy , Skin Neoplasms/mortality , Skin Neoplasms/pathology , Skin Neoplasms/radiotherapy , Male , Female , Aged , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Middle Aged , Aged, 80 and over , Immune Checkpoint Inhibitors/therapeutic use , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Follow-Up Studies , Chemoradiotherapy/methods
4.
Recenti Prog Med ; 115(5): 1e-6e, 2024 May.
Article in Italian | MEDLINE | ID: mdl-38708539

ABSTRACT

INTRODUCTION AND AIM: Locally advanced head and neck squamous cell carcinoma (LA-Hnscc) is a true therapeutical challenge in the modern era and the scientific community is trying to face this challenge with new therapeutical strategies, including combinations of monoclonal antibodies and radiation therapy. The aim of this study is to evaluate clinical outcomes in LA-Hnscc patients unfit to receive platinum-based chemotherapy, treated with concurrent simultaneous integrated boost-intensity modulated radiotherapy (Sib-Imrt) + cetuximab (Ctx) in daily clinical practice. METHODS: LA-Hnscc patients not included in other prospective studies treated in 4 Italian radiotherapy units (2 Messina, 1 Rome, and 1 Lecce) using Sib-Imrt and Ctx were included in this study. Acute and late toxicities and overall survival (OS) have been evaluated. RESULTS: Data regarding 27 patients with squamous tumour were collected and reviewed. The primary tumour sites were oropharynx in 14 patients (51.9%), oral cavity in 7 (25.9%), larynx in 3 (11%) and other sites in 3(11%). There were 20 (74%) patients had stage IV (16 IVa and 4 IVb). Complete remission was observed in 18 patients (66.7%), a partial remission in 4 (14.8%) whilst 4 had a progression disease (14.8%). After 3 year of follow-up 7/27 patients were deaths. The OS was 95.5%, 62.5% and 52.9% respectively at 1,2 and 3 years. Acute toxicities were observed in all treated patients (mucositis, dermatitis and dysphagia) while 66.7% of patients developed late toxicities. All observed toxicities were grade 1 to 3 and just 1 patient developed a G4 toxicity. CONCLUSION: The concurrent bio-radiotherapy of Sib-Imrt and cetuximab is feasible in real-life daily clinical practice for LA-Hnscc patients unfit for platinum-based chemoradiotherapy.


Subject(s)
Antineoplastic Agents, Immunological , Cetuximab , Chemoradiotherapy , Head and Neck Neoplasms , Radiotherapy, Intensity-Modulated , Squamous Cell Carcinoma of Head and Neck , Humans , Cetuximab/administration & dosage , Male , Female , Middle Aged , Aged , Head and Neck Neoplasms/radiotherapy , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/therapy , Head and Neck Neoplasms/drug therapy , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Squamous Cell Carcinoma of Head and Neck/therapy , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/pathology , Chemoradiotherapy/methods , Antineoplastic Agents, Immunological/administration & dosage , Radiotherapy, Intensity-Modulated/methods , Radiotherapy, Intensity-Modulated/adverse effects , Italy , Survival Rate , Adult , Treatment Outcome , Neoplasm Staging , Aged, 80 and over , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/drug therapy , Retrospective Studies
6.
BMC Oral Health ; 24(1): 519, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38698358

ABSTRACT

BACKGROUND: Oral cancer is a deadly disease and a major cause of morbidity and mortality worldwide. The purpose of this study was to develop a fuzzy deep learning (FDL)-based model to estimate the survival time based on clinicopathologic data of oral cancer. METHODS: Electronic medical records of 581 oral squamous cell carcinoma (OSCC) patients, treated with surgery with or without radiochemotherapy, were collected retrospectively from the Oral and Maxillofacial Surgery Clinic and the Regional Cancer Center from 2011 to 2019. The deep learning (DL) model was trained to classify survival time classes based on clinicopathologic data. Fuzzy logic was integrated into the DL model and trained to create FDL-based models to estimate the survival time classes. RESULTS: The performance of the models was evaluated on a test dataset. The performance of the DL and FDL models for estimation of survival time achieved an accuracy of 0.74 and 0.97 and an area under the receiver operating characteristic (AUC) curve of 0.84 to 1.00 and 1.00, respectively. CONCLUSIONS: The integration of fuzzy logic into DL models could improve the accuracy to estimate survival time based on clinicopathologic data of oral cancer.


Subject(s)
Deep Learning , Fuzzy Logic , Mouth Neoplasms , Humans , Mouth Neoplasms/pathology , Mouth Neoplasms/mortality , Retrospective Studies , Female , Male , Middle Aged , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/therapy , Survival Analysis , Aged , Survival Rate , Adult
7.
Laryngorhinootologie ; 103(S 01): S100-S124, 2024 May.
Article in English, German | MEDLINE | ID: mdl-38697144

ABSTRACT

The interdisciplinary treatment of skin cancer in the head and neck area requires close collaboration between different specialist disciplines. The most common non-melanoma skin cancer tumor entities are cutaneous squamous cell carcinoma and basal cell carcinoma as well as their precursor lesions. One of the less common tumors is Merkel cell carcinoma, which also occurs primarily in light-exposed areas and, in contrast to squamous and basal cell carcinoma, is more likely to metastasize. Due to the low tendency of basal cell carcinoma as well as cutaneous squamous cell carcinoma to metastasize, a cure can often be achieved by surgery. If the tumor growth exceeds certain levels it may require collaboration between dermatology and otorhinolaryngology. The primary goal of this interdisciplinary collaboration is to achieve a functional, cosmetically and aesthetically acceptable result in addition to adequate tumor treatment. Depending on the stage of the tumor and the clinical course, a case may be discussed in an interdisciplinary tumor board in order to determine a personalised, appropriate and adequate treatment concept for each patient, including prevention, therapy and follow-up.


Subject(s)
Carcinoma, Basal Cell , Carcinoma, Squamous Cell , Interdisciplinary Communication , Skin Neoplasms , Skin Neoplasms/therapy , Skin Neoplasms/pathology , Skin Neoplasms/surgery , Humans , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Carcinoma, Basal Cell/therapy , Carcinoma, Basal Cell/pathology , Carcinoma, Basal Cell/surgery , Patient Care Team , Carcinoma, Merkel Cell/therapy , Carcinoma, Merkel Cell/pathology , Carcinoma, Merkel Cell/surgery , Intersectoral Collaboration , Neoplasm Staging
8.
Head Neck ; 46(6): 1253-1262, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38600434

ABSTRACT

BACKGROUND: An international multidisciplinary panel of experts aimed to provide consensus guidelines describing the optimal intratumoral and intranodal injection of NBTXR3 hafnium oxide nanoparticles in head and neck squamous cell carcinoma (HNSCC) of the oral cavity, oropharynx, and cervical lymph nodes and to review data concerning safety, feasibility, and procedural aspects of administration. METHODS: The Delphi method was used to determine consensus. A 4-member steering committee and a 10-member monitoring committee wrote and revised the guidelines, divided into eight sections. An independent 3-member reading committee reviewed the recommendations. RESULTS: After two rounds of voting, strong consensus was obtained on all recommendations. Intratumoral and intranodal injection was deemed feasible. NBTXR3 volume calculation, choice of patients, preparation and injection procedure, potential side effects, post injection, and post treatment follow-up were described in detail. CONCLUSIONS: Best practices for the injection of NBTXR3 were defined, thus enabling international standardization of intratumoral nanoparticle injection.


Subject(s)
Head and Neck Neoplasms , Injections, Intralesional , Squamous Cell Carcinoma of Head and Neck , Humans , Head and Neck Neoplasms/therapy , Squamous Cell Carcinoma of Head and Neck/therapy , Delphi Technique , Hafnium/administration & dosage , Oxides/administration & dosage , Nanoparticles/administration & dosage , Male , Consensus , Female , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/pathology , Practice Guidelines as Topic
9.
JAMA Otolaryngol Head Neck Surg ; 150(5): 429-435, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38573597

ABSTRACT

Importance: Despite interest in therapy de-escalation for survivors of human papillomavirus-mediated oropharyngeal squamous cell carcinoma (HPV-positive OPSCC), the association of de-escalated therapy with patient-reported quality of life (QoL) outcomes and burden of depressive symptoms remains unclear. Objective: To identify associations between clinicopathologic and therapeutic variables with patient-reported QoL outcomes and depression symptom burden in patients with HPV-positive OPSCC, who were enrolled in a therapy de-escalation trial. Design, Setting, and Participants: In this nonrandomized controlled, open-label, curative-intent therapy de-escalation clinical trial in adults with stage I, II, and III HPV-positive OPSCC, patients were recruited from a high-volume head and neck oncology practice. Main Outcomes and Measures: The main outcomes of this study included quantitative, patient-reported QoL and depression symptoms per well-validated inventories. Patient-reported QoL was based on Functional Assessment of Cancer Therapy-Head & Neck (FACT-HN) scores (range, 0-148; lower score indicates inferior QoL). Patient-reported depression-related symptom burden was based on Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) scores (range, 0-27; a higher score indicates a higher burden of depression symptoms). Baseline clinicopathologic and treatment variables were paired with FACT-HN and QIDS-SR scores at baseline, 3, 6, 12, 24, and 36 months. Linear mixed-effect models with a random intercept were used for each participant and fixed effects for other measures. Regression coefficients are reported with 95% CIs. Results: A total of 95 patients were followed up for a median (IQR) of 2.2 (1.6-3.2) years. Of these, 93 patients (98%) were male with a mean (SD) age of 60.5 (8.2) years. Overall, 54 participants (57%) had a history of current or former smoking, 47 (50%) underwent curative-intent surgery (with or without adjuvant therapy), and 48 (50%) underwent primary radiotherapy (with or without chemotherapy). The median (IQR) radiotherapy dose was 60 (60-70) Gy. Five deaths and 2 recurrence events were observed (mean [SD] recurrence interval, 1.4 [1.5] years). A higher radiotherapy dose was the only modifiable factor associated with inferior patient-reported QoL (lower FACT-HN) (coefficient, -0.66 [95% CI, -1.09 to -0.23]) and greater burden of depression-related symptoms (higher QIDS-SR) (coefficient, 0.11 [95% CI, 0.04-0.19]). With the 70-Gy dose as reference, improvements in FACT-HN and QIDS-SR scores were identified when patients received 51 to 60 Gy (coefficient, 12.75 [95% CI, 4.58-20.92] and -2.17 [-3.49 to -0.85], respectively) and 50 Gy or lower (coefficient, 15.03 [4.36-25.69] and -2.80 [-4.55 to -1.04]). Conclusions and Relevance: In this nonrandomized controlled, open-label, curative-intent therapy de-escalation trial, a higher radiotherapy dose was associated with inferior patient-reported QoL and a greater burden of depression-related symptoms. This suggests opportunities for improved QoL outcomes and reduced depression symptom burden with a reduction in radiotherapy dose. Trial Registration: ClinicalTrials.gov Identifier: NCT04638465.


Subject(s)
Depression , Oropharyngeal Neoplasms , Papillomavirus Infections , Quality of Life , Humans , Male , Oropharyngeal Neoplasms/therapy , Oropharyngeal Neoplasms/virology , Oropharyngeal Neoplasms/psychology , Oropharyngeal Neoplasms/pathology , Female , Middle Aged , Depression/etiology , Papillomavirus Infections/complications , Papillomavirus Infections/psychology , Aged , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/virology , Carcinoma, Squamous Cell/psychology , Carcinoma, Squamous Cell/pathology , Patient Reported Outcome Measures , Neoplasm Staging
10.
J Photochem Photobiol B ; 255: 112907, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38677259

ABSTRACT

OBJECTIVE: The objective of this study is to investigate the variances in transcriptome gene expression of normal oral mucosa-derived mesenchymal stem cell (OM-MSC), oral leukoplakia-derived MSC (OLK-MSC) and oral squamous cell carcinoma-derived MSC(OSCC-MSC). as Additionally, the study aims to compare the in vitro proliferation, migration, invasion ability, and response to photodynamic therapy (PDT) of these three MSC, HOK, DOK, leuk1, and Cal27 cell lines. METHODS: HOK, DOK, leuk1, Cal27 cells were cultured in vitro. 3 MSC cells were obtained from OM, OLK, OSCC tissue (n = 3) and identified through flow cytometry. They were also cultured in vitro for osteogenic and lipogenic-induced differentiation. Based on the Illumina HiSeq high-throughput sequencing platform, OM-MSC, OLK-MSC, OSCC-MSC (n = 3) were subjected to transcriptome sequencing, functional annotation, and enrichment analysis of differentially expressed genes and related genes. CCK8 assay, wound healing assay, and transwell assay were performed to compare the proliferation, migration, and invasion of the seven types of cells. The 7 cells were incubated with 0, 0.125 mM, 0.25 mM, 0.5 mM, 1 mM, and 2 mM of the photosensitizer (5-aminolevulinic acid, 5-ALA) in vitro. Subsequently, they were irradiated with a 150 mM, 635 nm laser for 1 min, and the cell activity was detected using the CCK8 assay after 24 h. The mitochondrial changes in the 7 cells before and after the treatment of PDT were detected using the JC-10 probe, and the changes in ATP content were measured before and after the PDT treatment. RESULTS: OM-MSC, OLK-MSC, and OSCC-MSC expressed positive MSC surface markers. After osteogenic and lipogenic-induced differentiation culture, stained calcium nodules and lipid droplets were visible, meeting the identification criteria of MSC. Pathway enrichment analysis revealed that the differentially expressed genes (DEGs) of OSCC-MSC compared to OLK-MSC were primarily associated with the PI3K-Akt signaling pathway and tumor-related pathways. OSCC-MSC exhibited stronger migratory and invasive abilities compared to Cal27. The IC50 values required for OM, OLK, and OSCC-derived MSC were lower than those required for epithelial cells treated with PDT, which were 1.396 mM, 0.9063 mM, and 2.924 mM, respectively. Cell membrane and mitochondrial disruption were observed in seven types of cells after 24 h of PDT treatment. However, HOK, DOK, leuk1, and Cal27 cells had an ATP content increased. CONCLUSIONS: OLK, OSCC epithelial cells require higher concentrations of 5-ALA for PDT treatment than MSC of the same tissue origin. The concentration of 5-ALA required increases with increasing cell malignancy. Differences in the response of epithelial cells and MSC to PDT treatment may have varying impacts on OLK recurrence and malignancy.


Subject(s)
Carcinoma, Squamous Cell , Cell Movement , Cell Proliferation , Epithelial Cells , Leukoplakia, Oral , Mesenchymal Stem Cells , Mouth Mucosa , Mouth Neoplasms , Photochemotherapy , Humans , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects , Mouth Mucosa/pathology , Mouth Mucosa/cytology , Leukoplakia, Oral/pathology , Leukoplakia, Oral/therapy , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , Cell Movement/drug effects , Cell Movement/radiation effects , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/metabolism , Mouth Neoplasms/pathology , Mouth Neoplasms/metabolism , Mouth Neoplasms/drug therapy , Mouth Neoplasms/therapy , Epithelial Cells/cytology , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Photosensitizing Agents/pharmacology , Cell Line, Tumor , Aminolevulinic Acid/pharmacology , Cell Differentiation/drug effects , Transcriptome/drug effects
11.
Curr Treat Options Oncol ; 25(5): 619-627, 2024 May.
Article in English | MEDLINE | ID: mdl-38581550

ABSTRACT

OPINION STATEMENT: Skin tumors commonly seen in dermatology are involved in all layers of the skin and appendages. While biopsy of affected skin remains an essential method to confirm diagnosis and to predicate tumor prognosis, it has its limitations. Recently, photodynamic diagnosis (PDD) has demonstrated high sensitivity in detecting affected skin and mucosal tissues, providing valuable guidance for precision surgery to resect skin and mucosal tumors. In this review, we summarized the literatures concerning the applications of PDD in diagnostic process and treatment of skin and mucosal conditions such as actinic keratoses (AK), basal cell carcinoma (BCC), squamous cell carcinoma (SCC), Bowen's disease (BD) and extramammary Paget's disease (EMPD). The findings suggest that PDD holds substantial promise for expanding clinical applications and deserves further research exploration.


Subject(s)
Photochemotherapy , Skin Neoplasms , Humans , Skin Neoplasms/diagnosis , Skin Neoplasms/therapy , Skin Neoplasms/etiology , Photochemotherapy/methods , Carcinoma, Basal Cell/diagnosis , Carcinoma, Basal Cell/therapy , Disease Management , Photosensitizing Agents/therapeutic use , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/therapy
12.
Acta Derm Venereol ; 104: adv39927, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38629891

ABSTRACT

Narrow-band TL-01 ultraviolet B phototherapy (TL-01) is an effective and widely used treatment for many skin diseases. The purpose of the investigation was to assess the risk of skin cancers in patients treated with TL-01 phototherapy who have not received any other phototherapy modalities. This cohort study included 4,815 TL-01 treated patients in Finland with psoriasis or atopic dermatitis. Clinical information was collected from the hospital records and linked with Finnish Cancer Registry data. The follow-up started from the first TL-01 treatment and the mean follow-up time was 8.4 years. Standardized incidence ratios were calculated for basal cell carcinoma, cutaneous melanoma, and squamous cell carcinoma. The standardized incidence ratio for basal cell carcinoma was 2.5 (95% confidence interval 1.8-3.5), for cutaneous melanoma 4.0 (95% confidence interval 2.1-6.8) and for squamous cell carcinoma 3.7 (95% confidence interval 1.7-7.0). For basal cell carcinoma and squamous cell carcinoma, the standardized incidence ratios remained similar during the whole follow-up time while the standardized incidence ratio for cutaneous melanoma was markedly higher during the first 5 years of follow-up. In conclusion, an increased incidence of skin cancers was observed among TL-01 treated patients. It should be confirmed in the future whether the skin cancer risk of TL-01 phototherapy will remain high in a longer follow-up.


Subject(s)
Carcinoma, Basal Cell , Carcinoma, Squamous Cell , Melanoma , Psoriasis , Skin Neoplasms , Ultraviolet Therapy , Humans , Skin Neoplasms/epidemiology , Skin Neoplasms/etiology , Melanoma/epidemiology , Melanoma/complications , Cohort Studies , Phototherapy/adverse effects , Ultraviolet Therapy/adverse effects , Psoriasis/drug therapy , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/therapy , Carcinoma, Basal Cell/epidemiology , Carcinoma, Basal Cell/therapy
14.
Klin Monbl Augenheilkd ; 241(4): 402-405, 2024 Apr.
Article in German | MEDLINE | ID: mdl-38653294

ABSTRACT

BACKGROUND/OBJECTIVES: Ocular surface squamous neoplasia (OSSN) are among the most frequent non-pigmented malignancies of the ocular surface. They have a wide range of histological characteristics - ranging from mild epithelial dysplasia to invasive carcinoma of the squamous cells of the cornea. They may be restricted to the conjunctiva or also involve the cornea. As there are no leading symptoms in the early stages, diagnosis may be very delayed in patients who do not receive regular ophthalmological treatment. The present case series describes clinical and histological data on OSSN and includes clinical and histological data on OSSN, including possible clinical presentations, important risk factors, special histological and cytological features and therapeutic options. METHODS: Retrospective case series of patients with histologically confirmed severe epithelial dysplasia of the conjunctiva and cornea consistent with OSSN who presented to the Department of Ophthalmology in Basel University Hospital. The analysis covered demographic data, symptoms, diagnostic testing (photo documentation, brush biopsy), treatment and cytological and/or histological material and findings. RESULTS: We report on five patients aged between 41 and 92 years at the time of diagnosis. The histological findings in all patients included severe epithelial dysplasia, but with a heterogenous clinical presentation. In all cases, the lesion started in the conjunctiva, but traversed the limbus and extended to the cornea. The primary treatment was always surgical removal. In one patient, this had to be repeated several times due to recurrent metaplasia and was complemented by subsequent mitomycin C therapy. The clinical outcome ranged between total restitution of the original state to inevitable enucleation. CONCLUSION: The clinical presentation of OSSN is highly heterogenous, so that the initial diagnosis is difficult. There are no official guidelines for treatment, so that the treatment of choice varied between clinics. Regular ophthalmological follow-ups are recommended, even after complete surgical excision. Possible relevant concomitant diseases and risk factors must be identified before therapy.


Subject(s)
Conjunctival Neoplasms , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/surgery , Conjunctival Neoplasms/diagnosis , Conjunctival Neoplasms/pathology , Conjunctival Neoplasms/therapy , Corneal Diseases/diagnosis , Corneal Diseases/pathology , Corneal Diseases/therapy , Epithelium, Corneal/pathology , Eye Neoplasms/diagnosis , Eye Neoplasms/therapy , Eye Neoplasms/pathology , Eye Neoplasms/surgery , Retrospective Studies , Treatment Outcome
15.
Nanotheranostics ; 8(3): 285-297, 2024.
Article in English | MEDLINE | ID: mdl-38577322

ABSTRACT

Rationale: Microbubble (MB) contrast agents combined with ultrasound targeted microbubble cavitation (UTMC) are a promising platform for site-specific therapeutic oligonucleotide delivery. We investigated UTMC-mediated delivery of siRNA directed against epidermal growth factor receptor (EGFR), to squamous cell carcinoma (SCC) via a novel MB-liposome complex (LPX). Methods: LPXs were constructed by conjugation of cationic liposomes to the surface of C4F10 gas-filled lipid MBs using biotin/avidin chemistry, then loaded with siRNA via electrostatic interaction. Luciferase-expressing SCC-VII cells (SCC-VII-Luc) were cultured in Petri dishes. The Petri dishes were filled with media in which LPXs loaded with siRNA against firefly luciferase (Luc siRNA) were suspended. Ultrasound (US) (1 MHz, 100-µs pulse, 10% duty cycle) was delivered to the dishes for 10 sec at varying acoustic pressures and luciferase assay was performed 24 hr later. In vivo siRNA delivery was studied in SCC-VII tumor-bearing mice intravenously infused with a 0.5 mL saline suspension of EGFR siRNA LPX (7×108 LPX, ~30 µg siRNA) for 20 min during concurrent US (1 MHz, 0.5 MPa spatial peak temporal peak negative pressure, five 100-µs pulses every 1 ms; each pulse train repeated every 2 sec to allow reperfusion of LPX into the tumor). Mice were sacrificed 2 days post treatment and tumor EGFR expression was measured (Western blot). Other mice (n=23) received either EGFR siRNA-loaded LPX + UTMC or negative control (NC) siRNA-loaded LPX + UTMC on days 0 and 3, or no treatment ("sham"). Tumor volume was serially measured by high-resolution 3D US imaging. Results: Luc siRNA LPX + UTMC caused significant luciferase knockdown vs. no treatment control, p<0.05) in SCC-VII-Luc cells at acoustic pressures 0.25 MPa to 0.9 MPa, while no significant silencing effect was seen at lower pressure (0.125 MPa). In vivo, EGFR siRNA LPX + UTMC reduced tumor EGFR expression by ~30% and significantly inhibited tumor growth by day 9 (~40% decrease in tumor volume vs. NC siRNA LPX + UTMC, p<0.05). Conclusions: Luc siRNA LPXs + UTMC achieved functional delivery of Luc siRNA to SCC-VII-Luc cells in vitro. EGFR siRNA LPX + UTMC inhibited tumor growth and suppressed EGFR expression in vivo, suggesting that this platform holds promise for non-invasive, image-guided targeted delivery of therapeutic siRNA for cancer treatment.


Subject(s)
Carcinoma, Squamous Cell , Liposomes , Animals , Mice , Liposomes/chemistry , RNA, Small Interfering/genetics , Microbubbles , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/therapy , ErbB Receptors/genetics , Luciferases
16.
Crit Rev Oncog ; 29(3): 5-24, 2024.
Article in English | MEDLINE | ID: mdl-38683151

ABSTRACT

Squamous cell carcinoma of the oral cavity presents a significant global health burden, primarily due to risk factors such as tobacco smoking, smokeless tobacco use, heavy alcohol consumption, and betel quid chewing. Common clinical manifestations of oral cavity cancer include visible lesions and sores, often accompanied by pain in advanced stages. Diagnosis relies on a comprehensive assessment involving detailed history, physical examination, and biopsy. Ancillary imaging studies and functional evaluations aid in accurate staging and facilitate treatment planning. Prognostic information is obtained from histopathological factors, such as tumor grade, depth of invasion, lymphovascular invasion, and perineural invasion. Notably, lymph node metastasis, found in approximately half of the patients, carries significant prognostic implications. Effective management necessitates a multidisciplinary approach to optimize patient outcomes. Surgical resection is the backbone of treatment, aimed at complete tumor removal while preserving functional outcomes. Adjuvant therapies, including radiation and chemotherapy, are tailored according to pathological factors. Further work in risk stratification and treatment is necessary to optimize outcomes in squamous cell carcinoma of the oral cavity.


Subject(s)
Carcinoma, Squamous Cell , Mouth Neoplasms , Humans , Mouth Neoplasms/therapy , Mouth Neoplasms/diagnosis , Mouth Neoplasms/etiology , Mouth Neoplasms/pathology , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/etiology , Carcinoma, Squamous Cell/pathology , Disease Management , Prognosis , Risk Factors
17.
Int J Mol Sci ; 25(7)2024 Mar 23.
Article in English | MEDLINE | ID: mdl-38612418

ABSTRACT

Non-small-cell lung cancer (NSCLC) poses a challenge due to its heterogeneity, necessitating precise histopathological subtyping and prognostication for optimal treatment decision-making. Molecular markers emerge as a potential solution, overcoming the limitations of conventional methods and supporting the diagnostic-therapeutic interventions. In this study, we validated the expression of six genes (MIR205HG, KRT5, KRT6A, KRT6C, SERPINB5, and DSG3), previously identified within a 53-gene signature developed by our team, utilizing gene expression microarray technology. Real-time PCR on 140 thoroughly characterized early-stage NSCLC samples revealed substantial upregulation of all six genes in squamous cell carcinoma (SCC) compared to adenocarcinoma (ADC), regardless of clinical factors. The decision boundaries of the logistic regression model demonstrated effective separation of the relative expression levels between SCC and ADC for most genes, excluding KRT6C. Logistic regression and gradient boosting decision tree classifiers, incorporating all six validated genes, exhibited notable performance (AUC: 0.8930 and 0.8909, respectively) in distinguishing NSCLC subtypes. Nevertheless, our investigation revealed that the gene expression profiles failed to yield predictive value regarding the progression of early-stage NSCLC. Our molecular diagnostic models manifest the potential for an exhaustive molecular characterization of NSCLC, subsequently informing personalized treatment decisions and elevating the standards of clinical management and prognosis for patients.


Subject(s)
Adenocarcinoma , Carcinoma, Non-Small-Cell Lung , Carcinoma, Squamous Cell , Lung Neoplasms , Small Cell Lung Carcinoma , Humans , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/therapy , Diagnosis, Differential , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Lung Neoplasms/therapy , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/therapy
18.
Int J Mol Sci ; 25(7)2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38612815

ABSTRACT

This systematic review investigates the potential of circulating tumour DNA (ctDNA) as a predictive biomarker in the management and prognosis of squamous cell carcinoma of the anal canal (SCCA). PubMed, EMBASE, and Cochrane Central Registry of Controlled Trials were searched until 7 January 2024. Selection criteria included research articles exploring ctDNA in the context of anal cancer treatment response, recurrence risk assessment, and consideration of salvage surgery. A total of eight studies were therefore included in the final review, examining a total of 628 patients. These studies focused on three main themes: SCCA diagnosis and staging, treatment response, and patient outcomes. Significant heterogeneity was observed in terms of patient cohort, study methodology, and ctDNA biomarkers. Four studies provided information on the sensitivity of ctDNA biomarkers in SCCA, with a range of 82-100%. Seven studies noted a correlation between pre-treatment ctDNA levels and SCCA disease burden, suggesting that ctDNA could play a role as a biomarker for the staging of SCCA. Across all seven studies with paired pre- and post-treatment ctDNA samples, a trend was seen towards decreasing ctDNA levels post-treatment, with specific identification of a 'fast elimination' group who achieve undetectable ctDNA levels prior to the end of treatment and may be less likely to experience treatment failure. Residual ctDNA detection post-treatment was associated with poorer patient prognosis. This systematic review identifies the broad potential of ctDNA as a useful and decisive tool in the management of SCCA. Further analysis of ctDNA biomarkers that include larger patient cohorts is required in order to clearly evaluate their potential role in clinical decision-making processes.


Subject(s)
Anus Neoplasms , Carcinoma, Squamous Cell , Circulating Tumor DNA , Humans , Circulating Tumor DNA/genetics , Anus Neoplasms/diagnosis , Anus Neoplasms/genetics , Anus Neoplasms/therapy , Biomarkers , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/therapy
19.
BMC Pulm Med ; 24(1): 192, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38644505

ABSTRACT

BACKGROUND: Stenosis and obliteration of the pulmonary vein can be developed by multiple diseases and might cause hemoptysis. Traditional therapy including surgical procedure and conservative treatments might be inappropriate choices to manage massive hemoptysis. CASE PRESENTATION: A 64-year-old man, diagnosed with advanced stage IVA lung squamous cell carcinoma, presented with dyspnea and recurrent, massive hemoptysis. An initial contrast-enhanced computed tomography revealed a giant tumor in the left lung hilus and occlusion of the left superior pulmonary vein. Despite immediate selective bronchial artery embolization and simultaneous embolization of an anomalous branch of the internal thoracic artery, the massive hemoptysis continued. Subsequently, embolization of the left superior pulmonary artery was performed, achieving functional pulmonary lobectomy, which successfully treated the hemoptysis without relapse during a six-month follow-up. The patient continues to undergo cancer therapy and remains stable. CONCLUSIONS: This case successfully managed massive hemoptysis associated with lung cancer invasion into the pulmonary vein through functional pulmonary lobectomy via embolization of the corresponding pulmonary artery.


Subject(s)
Carcinoma, Squamous Cell , Embolization, Therapeutic , Hemoptysis , Lung Neoplasms , Pulmonary Artery , Tomography, X-Ray Computed , Humans , Hemoptysis/therapy , Hemoptysis/etiology , Male , Middle Aged , Embolization, Therapeutic/methods , Lung Neoplasms/complications , Lung Neoplasms/therapy , Pulmonary Artery/diagnostic imaging , Carcinoma, Squamous Cell/complications , Carcinoma, Squamous Cell/therapy , Pulmonary Veins/abnormalities , Pulmonary Veins/diagnostic imaging , Pneumonectomy
20.
Anticancer Res ; 44(5): 2009-2019, 2024 May.
Article in English | MEDLINE | ID: mdl-38677756

ABSTRACT

BACKGROUND/AIM: 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. This study aimed to meticulously investigate the clinical significance of serum SCC antigen levels in patients with locally advanced cervical squamous cell carcinoma (LACSC). PATIENTS AND METHODS: The study included patients who were diagnosed with local stage (T-stage) 1b3/2/3 LACSC and underwent initial treatment at our institute between January 2006 and December 2016 (T-1b3: n=30; T-2: n=75; T-3: n=34). The patients were divided into three groups based on pre-treatment SCC values, and differences in clinical background, laboratory and pathology findings, and prognosis were examined. RESULTS: No significant difference in the SCC distribution 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: three out of five recurrences; T-2: six out of seven recurrences; T-3: four out of eight recurrences), while most recurrences in the SCC-Low group were pelvic (T-1b3: two out of three recurrences; T-2: eight out of eight recurrences; T-3: three out of three recurrences). CONCLUSION: In LACSC, serum SCC antigen levels before treatment correlate strongly with the recurrence site. Patients with low levels should be closely monitored for local recurrence, whereas those with high levels warrant vigilance for distant recurrence.


Subject(s)
Antigens, Neoplasm , Carcinoma, Squamous Cell , Neoplasm Recurrence, Local , Serpins , Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/blood , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/therapy , Carcinoma, Squamous Cell/blood , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Middle Aged , Serpins/blood , Antigens, Neoplasm/blood , Prognosis , Aged , Adult , Neoplasm Recurrence, Local/blood , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Biomarkers, Tumor/blood , Clinical Relevance
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