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Hut AR, Boia ER, Para D, Iovanescu G, Horhat D, Mikša L, Chiriac M, Galant R, Motofelea AC, Balica NC. Laryngeal Cancer in the Modern Era: Evolving Trends in Diagnosis, Treatment, and Survival Outcomes. J Clin Med 2025; 14:3367. [PMID: 40429363 DOI: 10.3390/jcm14103367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2025] [Revised: 05/08/2025] [Accepted: 05/09/2025] [Indexed: 05/29/2025] Open
Abstract
Background/Objectives: Laryngeal cancer (LC), predominantly squamous cell carcinoma (SCC), represents a considerable health burden worldwide. Tumour subsite heterogeneity (supraglottic, glottic, subglottic) influences clinical behavior and outcomes. This review synthesizes current knowledge on epidemiology, risk factors, diagnostics, histological variants, biomarkers, treatment modalities, and survival. Results: This narrative review synthesizes current literature on the epidemiology, risk factors, diagnosis, histological variants, biomarkers, and prognosis of LC. The review highlights the critical influence of tumour sites (supraglottic, glottic, subglottic) on metastatic patterns and survival. Key risk factors of LC include tobacco and alcohol use, human papillomavirus (HPV) infection, and occupational exposures. The diagnostic process encompasses clinical examination, endoscopy, biopsy, and imaging. Several biomarkers that aid in diagnosis, treatment plan determination, and prognosis prediction have been established. These biomarkers include long noncoding RNAs, cell cycle regulators, apoptosis regulators, oncogenes, tumour suppressor genes, growth factor pathway components, angiogenic factors, structural proteins, sex hormone receptors, and immunological markers. Current treatment modalities range from organ-preserving surgery and radiotherapy to combined chemoradiotherapy and total laryngectomy. Finally, survival data are presented and stratified by stage and subsite. Conclusions: The review underscores the need for a multidisciplinary approach to LC management, integrating clinical, pathological, and molecular information to optimize patient outcomes.
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Affiliation(s)
- Alexandru-Romulus Hut
- Department of Doctoral Studies, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
- ENT Department, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
| | - Eugen Radu Boia
- ENT Department, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
- ENT Department, Emergency City Hospital, 300254 Timisoara, Romania
| | - Diana Para
- Department of Doctoral Studies, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
| | - Gheorghe Iovanescu
- ENT Department, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
| | - Delia Horhat
- ENT Department, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
- ENT Department, Emergency City Hospital, 300254 Timisoara, Romania
| | - Loredan Mikša
- ENT Department, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
| | - Maria Chiriac
- ENT Department, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
| | - Raphaël Galant
- Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, 20 Rue Leblanc, 75015 Paris, France
| | - Alexandru Catalin Motofelea
- Department of Doctoral Studies, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
- Center for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Nicolae Constantin Balica
- ENT Department, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
- ENT Department, Emergency City Hospital, 300254 Timisoara, Romania
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Aonta P, Jaiyangyeun P, Theerapan W, Srisampan S, Wongsali C, Kovitvadhi A, Jaroensong T. Investigation of Ki-67 and Clinical Outcome in Feline Nasal Adenocarcinoma Treated Using Hypofractionated Radiotherapy. Animals (Basel) 2024; 14:3573. [PMID: 39765477 PMCID: PMC11672515 DOI: 10.3390/ani14243573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 11/23/2024] [Accepted: 12/09/2024] [Indexed: 01/11/2025] Open
Abstract
Ki-67 has been reported as a prognostic marker in human cancers treated using RT. The current study investigated the prognostic significance of Ki-67 expression and its association with clinicopathological characteristics in 19 cats diagnosed with nasal adenocarcinoma and treated using hypofractionated RT. Data collected encompassed signalment, clinical signs, clinicopathological variables, treatment outcomes, and survival times. Median survival times (MST) were estimated using Kaplan-Meier curves and analyzed based on the log-rank test. Based on the results, white blood cell counts were significantly (p < 0.001) higher before treatment than after, although this was not associated with survival time. The overall MST was 550 days (range: 56-1118 days). Cats achieving a favorable response (complete or partial response) had significantly (p = 0.006) longer survival times (1055 days) than those with a poor response (stable or progressive disease; 369 days). Cats with high Ki-67 expression had significantly (p = 0.028) longer survival times (1055 days) than those with low Ki-67 expression (256 days). These results suggested that Ki-67 may be a potential prognostic factor for feline nasal adenocarcinoma.
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Affiliation(s)
- Premkamon Aonta
- Department of Companion Animal Clinical Sciences, Faculty of Veterinary Medicine, Kasetsart University, 50 Ngamwongwan Rd., Lat Yao, Chatuchak, Bangkok 10900, Thailand; (P.A.); (W.T.)
| | - Piraya Jaiyangyeun
- Kasetsart Veterinary Imaging and Radiotherapy Center, Faculty of Veterinary Medicine, Kasetsart University, 50 Ngamwongwan Rd., Lat Yao, Chatuchak, Bangkok 10900, Thailand;
| | - Wutthiwong Theerapan
- Department of Companion Animal Clinical Sciences, Faculty of Veterinary Medicine, Kasetsart University, 50 Ngamwongwan Rd., Lat Yao, Chatuchak, Bangkok 10900, Thailand; (P.A.); (W.T.)
- Kasetsart Veterinary Imaging and Radiotherapy Center, Faculty of Veterinary Medicine, Kasetsart University, 50 Ngamwongwan Rd., Lat Yao, Chatuchak, Bangkok 10900, Thailand;
| | - Supreeya Srisampan
- Center for Veterinary Diagnostic Laboratory-Bangkhen, Faculty of Veterinary Medicine, Kasetsart University, 50 Ngamwongwan Rd., Lat Yao, Chatuchak, Bangkok 10900, Thailand; (S.S.); (C.W.)
| | - Charuwan Wongsali
- Center for Veterinary Diagnostic Laboratory-Bangkhen, Faculty of Veterinary Medicine, Kasetsart University, 50 Ngamwongwan Rd., Lat Yao, Chatuchak, Bangkok 10900, Thailand; (S.S.); (C.W.)
| | - Attawit Kovitvadhi
- Department of Physiology, Faculty of Veterinary Medicine, Kasetsart University, 50 Ngamwongwan Rd., Lat Yao, Chatuchak, Bangkok 10900, Thailand;
| | - Tassanee Jaroensong
- Department of Companion Animal Clinical Sciences, Faculty of Veterinary Medicine, Kasetsart University, 50 Ngamwongwan Rd., Lat Yao, Chatuchak, Bangkok 10900, Thailand; (P.A.); (W.T.)
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Feghaly C, Challita R, Hadir HB, Mobayed T, Bitar TA, Harbi M, Ghorayeb H, El-Hassan R, Bodgi L. Bladder Cancer Treatments in the Age of Personalized Medicine: A Comprehensive Review of Potential Radiosensitivity Biomarkers. Biomark Insights 2024; 19:11772719241297168. [PMID: 39512649 PMCID: PMC11542137 DOI: 10.1177/11772719241297168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Accepted: 10/17/2024] [Indexed: 11/15/2024] Open
Abstract
Bladder cancer is one of the most frequently diagnosed cancers in men. While cystectomy remains the primary treatment, advances in radiotherapy and chemotherapy have highlighted the value of bladder-preserving strategies, which can also enhance patients' quality of life. Despise these advances, around 20% of patients may still require salvage cystectomy due to tumor radioresistance. This underscores the need to develop radiosensitivity predictive assays. Radiotherapy acts by inducing DNA damage, primarily through DNA double-strand breaks, which can significantly affect treatment outcomes if left unrepaired. In addition to activating DNA repair pathways, the response to radiation also involves the tumor microenvironment, cell death pathways, immune responses and different types of cell death and proliferation receptors. In recent years, personalized medicine, which tailors treatments to individual patients, has gained increasing attention in cancer care. The development of chemo- and radiosensitivity predictive assays has become a key focus of cancer research. Despite the potential impact of such assays on bladder cancer treatment, there is still no reliable test that can help clinicians and informs patients in choosing the best treatment. This review aims to highlight studies that attempted to characterize bladder cancer radiosensitivity and to discuss the potential biomarkers that could be used to develop bladder cancer radiosensitivity predictive assays.
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Affiliation(s)
- Charbel Feghaly
- Department of Radiation Oncology, American University of Beirut Medical Center, Beirut, Lebanon
| | - Rafka Challita
- Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut, Lebanon
| | - Hanine Bou Hadir
- Department of Radiation Oncology, American University of Beirut Medical Center, Beirut, Lebanon
| | - Tala Mobayed
- Department of Radiation Oncology, American University of Beirut Medical Center, Beirut, Lebanon
| | - Tarek Al Bitar
- Department of Radiation Oncology, American University of Beirut Medical Center, Beirut, Lebanon
| | - Mohammad Harbi
- Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut, Lebanon
| | - Hala Ghorayeb
- Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut, Lebanon
| | - Rana El-Hassan
- Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut, Lebanon
| | - Larry Bodgi
- Department of Radiation Oncology, American University of Beirut Medical Center, Beirut, Lebanon
- Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut, Lebanon
- U1296 Unit, “Radiation: Defense, Health and Environment”, Centre Léon-Bérard, Inserm, Lyon, France
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Chen W, Lin G, Chen Y, Cheng F, Li X, Ding J, Zhong Y, Kong C, Chen M, Xia S, Lu C, Ji J. Prediction of the Ki-67 expression level in head and neck squamous cell carcinoma with machine learning-based multiparametric MRI radiomics: a multicenter study. BMC Cancer 2024; 24:418. [PMID: 38580939 PMCID: PMC10996101 DOI: 10.1186/s12885-024-12026-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Accepted: 02/20/2024] [Indexed: 04/07/2024] Open
Abstract
BACKGROUND This study aimed to develop and validate a machine learning (ML)-based fusion model to preoperatively predict Ki-67 expression levels in patients with head and neck squamous cell carcinoma (HNSCC) using multiparametric magnetic resonance imaging (MRI). METHODS A total of 351 patients with pathologically proven HNSCC from two medical centers were retrospectively enrolled in the study and divided into training (n = 196), internal validation (n = 84), and external validation (n = 71) cohorts. Radiomics features were extracted from T2-weighted images and contrast-enhanced T1-weighted images and screened. Seven ML classifiers, including k-nearest neighbors (KNN), support vector machine (SVM), logistic regression (LR), random forest (RF), linear discriminant analysis (LDA), naive Bayes (NB), and eXtreme Gradient Boosting (XGBoost) were trained. The best classifier was used to calculate radiomics (Rad)-scores and combine clinical factors to construct a fusion model. Performance was evaluated based on calibration, discrimination, reclassification, and clinical utility. RESULTS Thirteen features combining multiparametric MRI were finally selected. The SVM classifier showed the best performance, with the highest average area under the curve (AUC) of 0.851 in the validation cohorts. The fusion model incorporating SVM-based Rad-scores with clinical T stage and MR-reported lymph node status achieved encouraging predictive performance in the training (AUC = 0.916), internal validation (AUC = 0.903), and external validation (AUC = 0.885) cohorts. Furthermore, the fusion model showed better clinical benefit and higher classification accuracy than the clinical model. CONCLUSIONS The ML-based fusion model based on multiparametric MRI exhibited promise for predicting Ki-67 expression levels in HNSCC patients, which might be helpful for prognosis evaluation and clinical decision-making.
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Affiliation(s)
- Weiyue Chen
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, 323000, China
| | - Guihan Lin
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, 323000, China
| | - Yongjun Chen
- Department of Radiology, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, China
| | - Feng Cheng
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, China
- Department of Head and Neck Surgery, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, China
| | - Xia Li
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, 323000, China
| | - Jiayi Ding
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, 323000, China
| | - Yi Zhong
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, 323000, China
| | - Chunli Kong
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, 323000, China
| | - Minjiang Chen
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, 323000, China
| | - Shuiwei Xia
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, 323000, China
| | - Chenying Lu
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, China.
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, 323000, China.
| | - Jiansong Ji
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, China.
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, 323000, China.
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Aras S, Ozkanli S, Erdem E, Gokalp S, Erdogan CE. Investigation of low and high dose rate X-ray effects on histopathological changes and prognostic importance of Ki-67 in laryngeal cancer radiotherapy. Appl Radiat Isot 2023; 197:110823. [PMID: 37116260 DOI: 10.1016/j.apradiso.2023.110823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Revised: 02/27/2023] [Accepted: 04/13/2023] [Indexed: 04/30/2023]
Abstract
The aim of this study is to analyze the effect on histopathological changes and Ki-67 expression levels of Flattening Filter (FF) and Flattening Filter Free (FFF) beams to investigate the radiobiological mechanisms underlying laryngeal cancer (LCa) post-radiotherapy (RT) on mice models. Forty adult NOD SCID gamma (NSG) mice models were randomly divided into four groups; the sham, LCa, FF-RT and FFF-RT groups. The head and neck region of mice in FF-RT and FFF-RT groups (LCa plus RT groups) were irradiated with a single dose of 18 Gy at 400 MU/min and 1400 MU/min. The NSG mice received radiotherapy 30 days after tumor transplantation and sacrificed 2 days after radiotherapy for analysis of histopathology parameters and K-67 expression levels. Comparing the LCa, FF-RT and FFF-RT groups with the sham group, statistically significant differences were observed in histopathological parameters depending on tumor tissue and dose rate (p < 0.05). When the histopathological effects of FF-RT beam on LCa tissue were compared with FFF-RT beam, it was observed that statistically significant differences occurred (p < 0.05). Comparing the LCa group with the sham group, it was observed that the Ki-67 level affected significantly depending on the development of cancer (p < 0.01). It was concluded that FF and FFF beams caused significant changes in the histopathological parameters and Ki-67 expression levels. When the effects of FFF beam on Ki-67 levels, cell nucleus and cytoplasmic findings were compared with FF beam, significant radiobiological differences were observed.
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Affiliation(s)
- Serhat Aras
- Medical Imaging Techniques Programme, University of Health Sciences Turkey, Istanbul, Turkey; Department of Radiation Oncology, Haydarpasa Numune Training and Research Hospital, University of Health Sciences Turkey, Istanbul, Turkey.
| | - Seyma Ozkanli
- Department of Pathology, Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkey
| | - Esra Erdem
- Pathology Laboratory Techniques Programme, University of Health Sciences Turkey, Istanbul, Turkey
| | - Sevtap Gokalp
- Department of Histology and Embryology, Maltepe University, Istanbul, Turkey
| | - Ceren Ezgi Erdogan
- Department of Radiation Oncology, Haydarpasa Numune Training and Research Hospital, University of Health Sciences Turkey, Istanbul, Turkey
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Vadlamudi Y, Dey DK, Kang SC. Emerging Multi-cancer Regulatory Role of ESRP1: Orchestration of Alternative Splicing to Control EMT. Curr Cancer Drug Targets 2021; 20:654-665. [PMID: 32564755 DOI: 10.2174/1568009620666200621153831] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Revised: 04/30/2020] [Accepted: 05/06/2020] [Indexed: 02/06/2023]
Abstract
RNA binding proteins (RBPs) associate with nascent and mature RNAs to perform biological functions such as alternative splicing and RNA stability. Having unique RNA recognition binding motifs, RBPs form complexes with RNA in a sequence- and structure-based manner. Aberrant expressions of several RBPs have been identified in tumorigenesis and cancer progression. These uncontrolled RBPs affect several mechanisms, including cell proliferation, tumor growth, invasion, metastasis and chemoresistance. Epithelial splicing regulatory protein 1 (ESRP1) is a member of the hnRNP family of proteins that play a crucial role in regulating numerous cellular processes, including alternative splicing and translation of multiple genes during organogenesis. Abnormal expression of ESRP1 alters the cell morphology, and leads to cell proliferation and tumor growth during cancer progression. ESRP1 mediated alternative splicing of target genes, including CD44, FGFR, PTBP1, LYN, ENAH, SPAG1 and ZMYND8, results in cancer progression. In addition, ESRP1 also regulates circularization and biogenesis of circular RNAs such as circUHRF1, circNOL10 and circANKS1B, whose expressions have been identified as key factors in various cancers. This multi-functional protein is also involved in imposing stability of target mRNAs such as cyclin A2, and thereby cell cycle regulation. The scope of this review is to examine recent scientific data, outcomes of the up- and down-regulated proteins, and the role of ESRP1 in various cancers. We conclude by summarizing ESRP1 dysregulation and its consequences on target genes in various human cancers. Collectively, the consequences of ESRP1 mediated splicing in cancer cells suggest the role of ESRP1 in cell proliferation and chemoresistance via apoptosis and autophagy modulation, which could, therefore, be potential targets for cancer therapeutics.
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Affiliation(s)
| | - Debasish K Dey
- Department of Biotechnology, Daegu University, Gyeongsan, Gyeongbuk-38453, Korea
| | - Sun C Kang
- Department of Biotechnology, Daegu University, Gyeongsan, Gyeongbuk-38453, Korea
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Cavaliere M, Bisogno A, Scarpa A, D'Urso A, Marra P, Colacurcio V, De Luca P, Ralli M, Cassandro E, Cassandro C. Biomarkers of laryngeal squamous cell carcinoma: a review. Ann Diagn Pathol 2021; 54:151787. [PMID: 34242969 DOI: 10.1016/j.anndiagpath.2021.151787] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Accepted: 06/30/2021] [Indexed: 10/21/2022]
Abstract
Laryngeal carcinoma is the second common malignancy of the upper aerodigestive tract after lung cancer; in most cases is a squamous cell carcinoma, whose risk factors include tobacco smoking and alcohol consumption. Despite therapeutic progress, the five-year overall survival rate for this malignancy has remained nearly 50% and many patients already present metastasis at the time of diagnosis. To date, there are no tools that predict the evolution of laryngeal carcinoma: in this light, during the last years, many studies were planned with the aim to investigate the role played by different biomarkers expressed by larynx cancer, which can help make an early diagnosis, predict disease evolution and direct therapeutic choice. This review aims to summarize these markers and correlating them with disease evolution.
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Affiliation(s)
- Matteo Cavaliere
- Department of Medicine and Surgery, University of Salerno, Via Salvador Allende 43, 84081 Baronissi, Salerno, Italy
| | - Antonella Bisogno
- Department of Medicine and Surgery, University of Salerno, Via Salvador Allende 43, 84081 Baronissi, Salerno, Italy.
| | - Alfonso Scarpa
- Department of Medicine and Surgery, University of Salerno, Via Salvador Allende 43, 84081 Baronissi, Salerno, Italy
| | - Alessia D'Urso
- Department of Medicine and Surgery, University of Salerno, Via Salvador Allende 43, 84081 Baronissi, Salerno, Italy
| | - Pasquale Marra
- Department of Medicine and Surgery, University of Salerno, Via Salvador Allende 43, 84081 Baronissi, Salerno, Italy
| | - Vito Colacurcio
- Department of Medicine and Surgery, University of Salerno, Via Salvador Allende 43, 84081 Baronissi, Salerno, Italy
| | - Pietro De Luca
- Department of Medicine and Surgery, University of Salerno, Via Salvador Allende 43, 84081 Baronissi, Salerno, Italy
| | - Massimo Ralli
- Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
| | - Ettore Cassandro
- Department of Medicine and Surgery, University of Salerno, Via Salvador Allende 43, 84081 Baronissi, Salerno, Italy.
| | - Claudia Cassandro
- Surgical Sciences Department, University of Turin, Corso Dogliotti 14, 10124 Turin, Italy
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Noordhuis MG, Kop EA, van der Vegt B, Langendijk JA, van der Laan BFAM, Schuuring E, de Bock GH. Biological tumor markers associated with local control after primary radiotherapy in laryngeal cancer: A systematic review. Clin Otolaryngol 2020; 45:486-494. [PMID: 32246586 PMCID: PMC7318351 DOI: 10.1111/coa.13540] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Revised: 02/11/2020] [Accepted: 03/22/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND The choice of treatment in laryngeal cancer is mainly based on tumor stage, post-treatment morbidity and quality of life. Biological tumor markers might also be of potential clinical relevance. OBJECTIVE OF THE REVIEW The aim was to systematically review the value of published biological tumor markers to predict local control in laryngeal cancer patients treated with definitive radiotherapy. TYPE OF REVIEW Systematic review. SEARCH STRATEGY PubMed, Embase, Cochrane Library. EVALUATION METHOD A literature search was performed using multiple terms for laryngeal cancer, radiotherapy, biological markers, detection methods and local control or survival. Studies regarding the relation between biological tumor markers and local control or survival in laryngeal cancer patients primarily treated with radiotherapy were included. Markers were clustered on biological function. Quality of all studies was assessed. Study selection, data extraction and quality assessment was performed by two independent reviewers. RESULTS A total of 52 studies out of 618 manuscripts, concerning 118 markers, were included. EGFR and P53 showed consistent evidence for not being predictive of local control after primary radiotherapy, whereas proliferation markers (ie high Ki-67 expression) showed some, but no consistent, evidence for being predictive of better local control. Other clusters of markers (markers involved in angiogenesis and hypoxia, apoptosis markers, cell cycle, COX-2 and DNA characteristics) showed no consistent evidence towards being predictors of local control after primary radiotherapy. CONCLUSIONS Cell proliferation could be of potential interest for predicting local control after primary radiotherapy in laryngeal cancer patients, whereas EGFR and p53 are not predictive in contrast to some previous analyses. Large diversity in research methods is found between studies, which results in contradictory outcomes. Future studies need to be more standardised and well described according to the REMARK criteria in order to have better insight into which biomarkers can be used as predictors of local control after primary radiotherapy.
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Affiliation(s)
- Maartje G. Noordhuis
- Dept. of Otorhinolaryngology/Head and Neck SurgeryUniversity Medical Center GroningenUniversity of GroningenGroningenThe Netherlands
| | - Emiel A. Kop
- Dept. of Otorhinolaryngology/Head and Neck SurgeryUniversity Medical Center GroningenUniversity of GroningenGroningenThe Netherlands
| | - Bert van der Vegt
- Dept. of Pathology and Medical BiologyUniversity Medical Center GroningenUniversity of GroningenGroningenThe Netherlands
| | - Johannes A. Langendijk
- Dept. of Radiation OncologyUniversity of GroningenUniversity Medical Center GroningenGroningenThe Netherlands
| | - Bernard F. A. M. van der Laan
- Dept. of Otorhinolaryngology/Head and Neck SurgeryUniversity Medical Center GroningenUniversity of GroningenGroningenThe Netherlands
| | - Ed Schuuring
- Dept. of Pathology and Medical BiologyUniversity Medical Center GroningenUniversity of GroningenGroningenThe Netherlands
| | - Geertruida H. de Bock
- Dept. of Epidemiology and StatisticsUniversity Medical Center GroningenUniversity of GroningenGroningenThe Netherlands
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Bruine de Bruin L, Schuuring E, de Bock GH, Slagter-Menkema L, Mastik MF, Noordhuis MG, Langendijk JA, Kluin PM, van der Laan BFAM. High pATM is Associated With Poor Local Control in Supraglottic Cancer Treated With Radiotherapy. Laryngoscope 2020; 130:1954-1960. [PMID: 32275333 PMCID: PMC7384019 DOI: 10.1002/lary.28641] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2019] [Revised: 02/09/2020] [Accepted: 03/02/2020] [Indexed: 01/25/2023]
Abstract
Objectives Most early stage laryngeal squamous cell carcinomas (LSCC) are treated with radiotherapy. Discovery of new biomarkers are needed to improve prediction of outcome after radiotherapy and to identify potential targets for systemic targeted therapy. The ataxia telangiectasia mutated (ATM) gene plays a critical role in DNA damage response induced by ionizing radiation. Methods The prognostic value of immunohistochemical expression of pATM, pChk2, and p53 were investigated in 141 patients with T1‐T2 LSCC curatively treated with external beam radiotherapy. Uni‐ and multivariable Cox regression analyses were performed to examine the relation between expression levels of markers and local control. Results Local control was significantly worse in cases with high levels of pATM (HR 2.14; 95% CI, 1.08–4.24; P = .03). No significant associations with local control were found for pChk2 and p53 expression. The association of high pATM expression with poor local control was only found for supraglottic LSCC (HR 10.9; 95% CI, 1.40–84.4; P = .02). Conclusion Our findings suggest a potential role for ATM in response to radiotherapy in early stage supraglottic LSCC and imply ATM inhibition as a possibility to improve response to radiotherapy. Level of Evidence NA Laryngoscope, 130: 1954–1960, 2020
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Affiliation(s)
- Leonie Bruine de Bruin
- Department of Otorhinolaryngology/Head and Neck Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Ed Schuuring
- Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Geertruida H de Bock
- Department of Epidemiology and Statistics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Lorian Slagter-Menkema
- Department of Otorhinolaryngology/Head and Neck Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.,Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Mirjam F Mastik
- Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Maartje G Noordhuis
- Department of Otorhinolaryngology/Head and Neck Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Johannes A Langendijk
- Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Philip M Kluin
- Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Bernard F A M van der Laan
- Department of Otorhinolaryngology/Head and Neck Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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10
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Kop E, de Bock GH, Noordhuis MG, Slagter-Menkema L, van der Laan BFAM, Langendijk JA, Schuuring E, van der Vegt B. Standardised Ki-67 proliferation index assessment in early-stage laryngeal squamous cell carcinoma in relation to local control and survival after primary radiotherapy. Clin Otolaryngol 2019; 45:12-20. [PMID: 31561282 PMCID: PMC6973088 DOI: 10.1111/coa.13449] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Accepted: 09/08/2019] [Indexed: 12/24/2022]
Abstract
Objectives Ambiguous results have been reported on the predictive value of the Ki‐67 proliferation index (Ki‐67 PI) regarding local control (LC) and survival after primary radiotherapy (RT) in early‐stage laryngeal squamous cell cancer (LSCC). Small study size, heterogenic inclusion, variations in immunostaining and cut‐off values are attributing factors. Our aim was to elucidate the predictive value of the Ki‐67 PI for LC and disease‐specific survival (DSS) using a well‐defined series of T1‐T2 LSCC, standardised automatic immunostaining and digital image analysis (DIA). Methods A consecutive and well‐defined cohort of 208 patients with T1‐T2 LSCC treated with primary RT was selected. The Ki‐67 PI was determined using DIA. Mann‐Whitney U‐tests, logistic and Cox regression analyses were performed to assess associations between Ki‐67 PI, clinicopathological variables, LC and DSS. Results In multivariate Cox regression analysis, poor tumour differentiation (HR 2.20; 95% CI 1.06‐4.59, P = .04) and alcohol use (HR 2.84, 95% CI 1.20‐6.71; P = .02) were independent predictors for LC. Lymph node positivity was an independent predictor for DSS (HR 3.16, 95% CI 1.16‐8.64; P = .03). Ki‐67 PI was not associated with LC (HR 1.59; 95% CI 0.89‐2.81; P = .11) or DSS (HR 0.98; 95% CI 0.57‐1.66; P = .97). In addition, continuous Ki‐67 PI was not associated with LC (HR 2.03; 95% CI 0.37‐11.14, P = .42) or DSS (HR 0.62; 95% CI 0.05‐8.28; P = .72). Conclusion The Ki‐67 PI was not found to be a predictor for LC or DSS and therefore should not be incorporated in treatment‐related decision‐making for LSCC.
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Affiliation(s)
- Emiel Kop
- Department of Otorhinolaryngology, University Medical Center Groningen, Groningen, The Netherlands
| | - Geertruida H de Bock
- Department of Epidemiology, University of Groningen, University Medical Hospital Groningen, Groningen, The Netherlands
| | - Maartje G Noordhuis
- Department of Otorhinolaryngology, University Medical Center Groningen, Groningen, The Netherlands
| | - Lorian Slagter-Menkema
- Department of Otorhinolaryngology, University Medical Center Groningen, Groningen, The Netherlands
| | | | - Johannes A Langendijk
- Department of Radiotherapy, University of Groningen, University Medical Hospital Groningen, Groningen, The Netherlands
| | - Ed Schuuring
- Department of Pathology & Medical Biology, University of Groningen, University Medical Hospital Groningen, Groningen, The Netherlands
| | - Bert van der Vegt
- Department of Pathology & Medical Biology, University of Groningen, University Medical Hospital Groningen, Groningen, The Netherlands
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11
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The Relevance of Assessing the Cell Proliferation Factor Ki-67 in Squamous Cell Carcinoma of the Larynx. BIOMED RESEARCH INTERNATIONAL 2019; 2019:8142572. [PMID: 30766887 PMCID: PMC6350589 DOI: 10.1155/2019/8142572] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/06/2018] [Accepted: 12/20/2018] [Indexed: 11/18/2022]
Abstract
The aim of study was to investigate the expression of the proliferation factor Ki-67 and its relationship with histological grade, cancer stage, and treatment outcome in squamous cell carcinoma of the larynx. Samples from 78 patients with laryngeal cancer were analysed retrospectively. Paraffin sections of tumors were immunohistochemically stained for Ki-67 expression. The patients were divided in two groups according to the proliferative factor values (a low Ki-67 index group - Ki-67≤34 and high Ki-67 index group-Ki-67 >34). Statistical analysis of the data shows significant correlation among histological tumor grade and the value of the Ki-67 proliferative index. There was no correlation between tumoral Ki-67 expression and diagnosis, stage of the disease, or treatment outcome. In conclusion, Ki-67 expression in laryngeal cancer is not the most reliable marker for making precise diagnosis and predicting the clinical course.
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12
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Fu DR, Kato D, Endo Y, Kadosawa T. Apoptosis and Ki-67 as predictive factors for response to radiation therapy in feline nasal lymphomas. J Vet Med Sci 2016; 78:1161-6. [PMID: 27086717 PMCID: PMC4976272 DOI: 10.1292/jvms.15-0693] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Nasal lymphoma is the most common nasal tumor in cats and is generally a solitary and
radiosensitive tumor. We retrospectively evaluated the response to radiation and survival
time in relation to apoptosis and Ki-67 indices in feline nasal lymphomas treated with
radiation therapy. The apoptotic and Ki-67 indices were evaluated with TUNEL and
immunohistochemical staining in 30 biopsy tissues that were taken before any treatment.
These two indices were compared, and differences between different treatment response
groups were analyzed. The correlation between the median survival times (MST) and the
indices was estimated using the Kaplan Meier method, and statistical differences between
survival curves were analyzed using a log-rank method. With regard to apoptotic index, a
statistical difference was observed between the samples taken from cats with complete
response and stable disease (1.22% vs. 0.45%; P=0.045). The Ki-67 index
in cats with both complete response and partial response was significantly higher than in
cats with stable disease (44.4% and 39.6% vs. 16.3%; P<0.001 and
P=0.008, respectively). The cats with a high level of apoptosis
(>0.9%) nasal lymphoma were not significantly prolonged MSTs
(P=0.202), however, high Ki-67-positive (>40%) cats experienced a
statistically significant relationship with longer survival time
(P=0.015). Our results indicate that spontaneous apoptotic and Ki-67
indices are strong predictors for response to radiation therapy in feline nasal
lymphomas.
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Affiliation(s)
- Dah-Renn Fu
- Laboratory of Veterinary Clinical Oncology, Small Animal Clinical Sciences, Graduate School of Veterinary Medicine, Rakuno Gakuen University, 582 Midorimachi, Bunkyodai, Ebetsu, Hokkaido 069-8501, Japan
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13
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The challenge of blocking a wider family members of EGFR against head and neck squamous cell carcinomas. Oral Oncol 2015; 51:423-30. [PMID: 25753560 DOI: 10.1016/j.oraloncology.2015.02.092] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2014] [Revised: 02/16/2015] [Accepted: 02/17/2015] [Indexed: 12/22/2022]
Abstract
Head and neck squamous cell carcinoma (HNSCC) represent 95% of head and neck cancer with an incidence of over half a million people globally. The prognosis for patients with recurrent or metastatic HNSCC is generally poor with low 5-year survival rates despite treatment advances over the past few decades. Consequently, it is essential to search for new biomarkers and effective therapy options to optimize HNSCC treatment. Epidermal growth factor receptor (EGFR) is overexpressed in approximately 90% of tumours. EGFR has become one of most common targets for new therapies being investigated in HNSCC. In this way, multiple therapies targeting EGFR in HNSCC have been tested but response rates are still low especially in the recurrent or metastatic setting. This has been attributed to mechanisms of resistance to EGFR-targeted therapies. Afatinib, an oral small molecule ErbB Family Blocker that irreversibly binds to ErbB1 (EGFR), ErbB2 (HER2) and ErbB4 (HER4), is being investigated in HNSCC treatment with encouraging phase II results and several ongoing phase III trials. Results of these trials will help to understand the place of afatinib in the HNSCC treatment armamentarium.
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14
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Bonhin RG, Carvalho GMD, Guimarães AC, Chone CT, Crespo AN, Altemani AMDAM, Amstalden EMI. Histologic correlation of expression of Ki-67 in squamous cell carcinoma of the glottis according to the degree of cell differentiation. Braz J Otorhinolaryngol 2014; 80:290-5. [PMID: 25183178 PMCID: PMC9444666 DOI: 10.1016/j.bjorl.2014.05.016] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2013] [Accepted: 03/11/2014] [Indexed: 12/01/2022] Open
Abstract
Introduction Squamous cell carcinoma is the most common neoplasm of the larynx and glottis, and its prognosis depends on the size of the lesion, level of local invasion, cervical lymphatic spread, and presence of distant metastases. Ki-67 (MKI67) is a protein present in the core, whose function is related to cell proliferation. Aim To evaluate the expression of marker Ki-67 in squamous cell carcinoma of the larynx and glottis and its correlation to pathological findings. Methods Experimental study with immunohistochemistry analysis of Ki-67, calculating the percentage of the cell proliferation index in glottic squamous cell carcinomas. Results Sixteen cases were analyzed, with six well-differentiated and 10 poorly/moderately differentiated tumors. There was a correlation between cell proliferation index and degree of cell differentiation, with higher proliferation in poorly/moderately differentiated tumors. Conclusion The cell proliferation index, as measured by Ki-67, may be useful in the characterization of histological degree in glottic squamous cell tumors.
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Affiliation(s)
- Rodrigo Gonzalez Bonhin
- Discipline of Otorhinolaryngology, Head and Neck, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil.
| | | | - Alexandre Caixeta Guimarães
- Discipline of Otorhinolaryngology, Head and Neck, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil
| | - Carlos Takahiro Chone
- Discipline of Otorhinolaryngology, Head and Neck, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil
| | - Agrício Nubiato Crespo
- Discipline of Otorhinolaryngology, Head and Neck, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil
| | | | - Eliane M I Amstalden
- Department of Pathology, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil
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15
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Gioacchini FM, Alicandri-Ciufelli M, Magliulo G, Rubini C, Presutti L, Re M. The clinical relevance of Ki-67 expression in laryngeal squamous cell carcinoma. Eur Arch Otorhinolaryngol 2014; 272:1569-76. [PMID: 24890978 DOI: 10.1007/s00405-014-3117-0] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2014] [Accepted: 05/20/2014] [Indexed: 12/31/2022]
Abstract
The aim of this study was to determine the prognostic value of Ki-67 immunostaining in patients affected by laryngeal squamous cell carcinoma. A systematic review was carried out in a tertiary university referral center. An appropriate string was run on PubMed to retrieve articles dealing with Ki-67 immunohistochemical staining and laryngeal squamous cell carcinoma. A double cross-check was performed on citations and full-text articles by two investigators independently to review all manuscripts and perform a comprehensive quality assessment. Of 85 abstracts identified, 18 articles were included. These studies reported on 1,342 patients with histological confirmed diagnosis of laryngeal squamous cell carcinoma. Most studies showed a statistical association between Ki-67 immunohistochemical expression and at least one of the clinical and histopathological parameters considered by the authors. Overall the studies analyzed suggested that the tumoral proliferative index was statistically connected respectively with T stage (2/18), N stage (4/18), grading (6/18), disease-free survival (10/18) and overall survival (4/18). Our review strongly suggests that immunohistochemical staining of Ki-67 correlates with tumoral aggressiveness and worse prognosis in patients affected by laryngeal squamous cell carcinoma. Further high-quality prospective studies should be carried out to confirm our finding and determine the eventual differences between cancers of specific laryngeal subsites.
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Yang XD, Huang P, Wang F, Xu ZK. Expression of granulocyte colony-stimulating factor receptor in rectal cancer. World J Gastroenterol 2014; 20:1074-1078. [PMID: 24574781 PMCID: PMC3921532 DOI: 10.3748/wjg.v20.i4.1074] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2013] [Revised: 09/25/2013] [Accepted: 11/13/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate whether granulocyte colony-stimulating factor receptor (G-CSFR) expression before preoperative irradiation can predict the radiosensitivity of rectal cancer.
METHODS: The expression of G-CSFR was examined, using immunohistochemistry, in biopsy specimens from 126 patients with locally advanced rectal adenocarcinoma before preoperative irradiation. Radiosensitivity was then evaluated according to the Rectal Cancer Regression Grading. Endoscopic inspection was used to detect the tumor area in each patient. General patient information, such as age, gender, lymph node status, tumor size and degree of differentiation was recorded. A statistical analysis was then performed to evaluate the correlation between clinical or pathological parameters and G-CSFR expression in tumors.
RESULTS: According to endoscopic inspection, the tumor area ranged from 4 to 48 cm2 (median, 15 cm2). Positive G-CSFR immunoreactions (G-CSFR+) were observed in 85 specimens, and negative (G-CSFR-) in 41. No significant differences were found in age, gender, tumor invasion, lymph node status and tumor size between G-CSFR+ and G-CSFR- patients. G-CSFR expression was positively correlated with poor radiotherapy response (58.8% vs 75.6%, P = 0.014, r = 0.219). The proportion of well-differentiated tumors in G-CSFR+ and G-CSFR- patients was 24.7% and 36.6%, respectively. Sphincter preservation was observed in 57.6% of G-CSFR+ patients and 78.5% of G-CSFR- patients. Significant correlations were found between G-CSFR expression and tumor differentiation (24.7% vs 36.6%, P = 0.019, r = 0.210), as well as sphincter preservation (57.6% vs 78.5%, P = 0.044, r = 0.180).
CONCLUSION: The expression of G-CSFR before preoperative irradiation may predict the radiosensitivity of rectal cancer.
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17
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Lionello M, Staffieri A, Marioni G. Potential prognostic and therapeutic role for angiogenesis markers in laryngeal carcinoma. Acta Otolaryngol 2012; 132:574-82. [PMID: 22497582 DOI: 10.3109/00016489.2011.652308] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Angiogenesis is a hallmark of cancer, fundamental to its growth. The 'angiogenic switch' occurs when pro-angiogenic factors are not balanced by anti-angiogenic factors. A correlation between angiogenic properties and oncological prognosis (for laryngeal squamous cell carcinoma (LSCC) too) was first hypothesized in the 1990s. An exhaustive literature review was performed to investigate available data on angiogenesis markers and their biological role and therapeutic potential in LSCC. The prognostic significance of microvascular density in LSCC was investigated with endothelial targets, e.g. CD105, CD34, and CD31. Epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), VEGF receptor 2, angiogenin, hypoxia-inducible factor 1, and other biological markers were also studied. Only anti-EGFR therapy has been approved by the USFood and Drug Administration (FDA) for head and neck carcinoma in recent years, while several agents interfering with VEGF and its receptors are being studied. Experimental findings indicate that anti-CD105 monoclonal antibodies efficiently inhibit tumor angiogenesis. There are two main ways to approach the vascular profile of solid malignancies: by inhibiting new vessel formation (anti-angiogenic therapy) or selectively damaging neoplastic vessels (vascular targeting therapy). In advanced LSCC, both these strategies seem promising and warrant further preclinical and clinical investigation.
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Affiliation(s)
- Marco Lionello
- Department of Neurosciences, Otolaryngology Section, University of Padova, Padova, Italy
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18
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Hirasawa N, Itoh Y, Ishihara S, Kubota S, Itoh J, Fujimoto Y, Nakashima T, Naganawa S. Radiotherapy with or without chemotherapy for patients with T1-T2 glottic carcinoma: retrospective analysis. HEAD & NECK ONCOLOGY 2010; 2:20. [PMID: 20673360 PMCID: PMC2919535 DOI: 10.1186/1758-3284-2-20] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/06/2010] [Accepted: 07/30/2010] [Indexed: 11/10/2022]
Abstract
BACKGROUND To assess the results for local control (LC) and survival in patients with early-stage glottic cancer (GC) who were treated by radiotherapy (RT) with or without chemotherapy. METHODS Fifty-eight patients with T1-T2 squamous cell carcinoma of the glottis who were treated between 2001 and 2006 were analyzed retrospectively. Potential prognostic factors for LC were evaluated by univariate analysis. RESULTS The 5-year LC rate in all patients was 84.3%. The overall 5-year LC rates for patients with T1a, Tb, and T2 GC were 85.9%, 83%, and 85%, respectively. Of the 58 patients, eight developed recurrent disease at the primary site, and one had lymph node recurrences on the neck. In the final analysis, the total laryngectomy-free survival rate was 93% at five years, and the ultimate LC rates for T1a, Tb, and T2 were 100%, 90.9%, and 95.2%, respectively. In a univariate analysis of 55 patients, there was no statistical significance between the LC rate for RT alone and that for chemoradiation. Only two patients died of laryngeal carcinoma, and one died of intercurrent disease. Fifty-five patients were living disease-free at the end of the study period. The 5-year overall survival (OS) rate for all patients was 88.1%, and the 5-year OS rates for T1a, Tb, and T2 were 91.6%, 77.8%, and 89.9%, respectively. CONCLUSIONS The retrospective analysis showed a high rate of LC and larynx preservation in patients with T1-T2 GC by means of RT with or without chemotherapy. There was, however, no statistical difference in LC rates for the two types of therapy.
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Affiliation(s)
- Naoki Hirasawa
- Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya 4668550, Aichi, Japan
| | - Yoshiyuki Itoh
- Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya 4668550, Aichi, Japan
| | - Shunichi Ishihara
- Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya 4668550, Aichi, Japan
| | - Seiji Kubota
- Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya 4668550, Aichi, Japan
| | - Junji Itoh
- Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya 4668550, Aichi, Japan
| | - Yasushi Fujimoto
- Department of Otolaryngology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya 4668550, Aichi, Japan
| | - Tsutomu Nakashima
- Department of Otolaryngology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya 4668550, Aichi, Japan
| | - Shinji Naganawa
- Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya 4668550, Aichi, Japan
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Relationship between growth fraction and clonogenic survival after ionizing irradiation in pancreatic MiaPaCa2 cells. Acta Med Litu 2009. [DOI: 10.2478/v10140-009-0006-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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