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Objectives: Clinical extranodal extension (cENE) is a cN modifier in TNM-8 for laryngo-hypopharygeal carcinoma (LHC). We hypothesize that image-detected ENE (iENE) can provide additional prognostic value over cENE in LHC., Methods: Baseline CTs/MRIs of cN+ LHC patients treated with definitive (chemo-)radiotherapy between 2010-2019 were re-reviewed by a neuroradiologist using internationally accepted criteria for iENE-positive/negative (iENE+/iENE-). Overall survival (OS) was compared by iENE status. Multivariable analysis (MVA) was performed to confirm the prognostic value of iENE, adjusted for known potential confounders., Results: A total of 232 LHC patients were identified, including 154 iENE-/cENE-, 60 iENE+/cENE-, and 18 iENE+/cENE+. A higher proportion of iENE+ (vs iENE-) patients had lymph node (LN) size > 3 cm [53 (67 %) vs 4 (3 %)], >=5 LNs [51 (65 %) vs 33 (21 %)], and retropharyngeal LN [12 (15 %) vs 6 (4 %)] (all p < 0.01). Median follow-up was 4.8 years. iENE+/cENE- and iENE+/cENE+patients had similarly low 5-year OS [28 % (18-44) and 29 % (13-63)] vs iENE-/cENE- [53 % (45-62)] (p < 0.001). On MVA, mortality risk was higher with iENE+vs iENE- [hazard ratio (HR) 2.22 (95 % CI 1.47-3.36)]. The prognostic value of iENE remained with MVA in larynx (n = 124) (HR 2.51 [1.35-4.68], p = 0.004] or hypopharynx (n = 108) (HR 1.87 [1.02-3.43], p = 0.04) patients, separately., Conclusions: Our study confirms the independent prognostic importance of iENE for LHC following definitive (chemo-)radiotherapy beyond TNM-8 cN status that already contains the cENE parameter. Further research is needed to explore whether iENE could replace cENE for future cN classification., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Laryngeal squamous cell carcinoma (LSCC) with a high incidence and mortality rate, has a serious impact worldwide. Phosphofructokinase-1 liver type (PFKL) is a major enzyme in glycolysis progress, but its role in modulating tumorigenesis and cisplatin (DDP) chemosensitivity of LSCC was still unclear. The mRNA and protein levels of PFKL were detected by qRT-PCR and immunohistochemical assay. Cell Counting Kit-8 assay and flow cytometry were carried out to observe cell viability, as well as apoptosis and mitochondrial reactive oxygen species (mito-ROS). Extracellular acidification rate and lactate content were measured using extracellular flux analysis and lactate assay kit. Immunofluorescent staining was used to evaluate the expression of γ-H2AX foci. DNA damage was detected via single-cell gel electrophoresis. Western blotting was introduced to evaluate the protein level of PFKL, LDHA, γ-H2AX, cleaved PARP, H3K27ac, and H3K9ac. Mice xenograft model of LSCC was built for in vivo validation. The PFKL expression was significantly increased in LSCC and associated with poor survival of LSCC patients. Knockdown of PFKL in LSCC cells significantly inhibited cell viability, ECAR, lactate content, and LDHA expression, but promoted mito-ROS level. Furthermore, knockdown of PFKL enhanced response of LSCC cells to DDP by increasing DDP-induced apoptosis, promoting DDP-induced mito-ROS level, γ-H2AX foci, tail DNA, and the expression of γ-H2AX and cleaved PARP. However, the overexpression of PFKL in LSCC cells had opposite experimental results. Nude mice tumor formation experiment proved that downregulation of PFKL significantly enhanced response of cells to DDP, demonstrated by reduced tumor volume, weight and increased TUNEL-positive cells. Suppression of CBP/EP300-mediated PFKL transcription inhibited cell viability and glycolysis and promoted mito-ROS in LSCC. PFKL promotes cell viability and DNA damage repair in DDP-treated LSCC through regulation of glycolysis pathway., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare that are relevant to the content of this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The aim of this multicenter study was to evaluate the effectiveness and safety of electrochemotherapy (ECT) for the treatment of mucosal tumors in the head and neck. A total of 71 patients with 84 nodules of different histologies in the oral cavity, pharynx and larynx treated by ECT were evaluated. The data were collected from the InspECT database from 10 participating centers throughout Europe. Primary and recurrent/secondary tumors of different histologies were treated. The overall response rate was 65 %, with a 33 % complete response rate with limited side effects. The response rates of the primary and secondary tumors were not different. However, smaller tumors responded better than tumors larger than 3 cm in diameter. Furthermore, the tumors that were treated with curative intent responded significantly better than those treated with palliative intent. This study demonstrated the feasibility, safety and effectiveness of ECT in a larger cohort of patients with mucosal lesions in the head and neck region. Based on the available data, ECT can be used for the treatment of recurrent and, in some cases, primary mucosal tumors located in the oral cavity, larynx, and pharynx. A better response was obtained in patients with smaller primary tumors treated with curative intent., Competing Interests: Declaration of competing interest Francesca de Terlizzi is an IGEA employer. No other authors have conflicts of interest. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Neoadjuvant chemotherapy for induction selection of definitive treatment (IS) protocols have shown excellent outcomes for organ preservation and survival in patients with T3 laryngeal squamous cell carcinoma (LSCC). We seek to evaluate survival and organ preservation outcomes in T4 LSCC patients treated with IS protocols., Methods: Retrospective cohort of advanced T3 and T4 LSCC patients who underwent IS protocols based upon potential for preserving a functional larynx. Patients received one neoadjuvant cycle of platinum-based chemotherapy with either 5-fluorouracil or docetaxel or with two cycles of platinum-based chemotherapy with docetaxel and a Bcl-2 inhibitor. Patients who achieved ≥ 50 % response as determined by radiographic review and/or endoscopic evaluation received definitive chemoradiation. Patients who had < 50 % response after IS underwent total laryngectomy (TL) followed by post-operative radiation +/- chemotherapy., Results: Amongst T4 patients, 114 met inclusion criteria including 89 who underwent IS protocols and 25 who received an upfront TL. In total, 76.0 % of T3 patients and 71.9 % of T4 patients responded to IS and underwent definitive chemoradiation. There was no significant difference in hazard of death between T4 IS and T4 TL patients (HR: 0.9, p = 0.86). Among responders, there was no significant difference in 5-year laryngectomy-free survival (T3 - 59.6 %, T4 44.3 %, p = 0.15) or laryngeal preservation by T stage (T3 - 72.8 %, T4 - 73.0 %, p = 0.84)., Conclusions: Select T4 patients may benefit from organ preservation using IS protocols with similar response rates to patients with T3 tumors, without compromising survival when compared to upfront TL., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Although surgery is an important treatment for laryngeal cancer, surgery has a significant negative impact on the quality of life of patients, and many patients have poor tolerance to surgery. Therefore, alternative chemotherapeutic drugs are an important research hotspot. Chidamide is a histone deacetylase inhibitor that selectively inhibits the expression of type I and IIb histone deacetylases (1, 2, 3 and 10). It has a significant anticancer effect on a variety of solid tumours. This study verified the inhibitory effect of chidamide on laryngeal carcinoma. We conducted a variety of cellular and animal experiments to explore how chidamide inhibits the development of laryngeal cancer. The results showed that chidamide had significant antitumour activity against laryngeal carcinoma cells and xenografts and could induce cell apoptosis, ferroptosis and pyroptosis. This study provides a potential option for the treatment of laryngeal cancer., Competing Interests: Declaration of Competing Interest The authors declare that the participants in this study have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Previously, we demonstrated that the combined mode of carboplatin (CBDCA) and photodynamic therapy (PDT) based on 9-hydroxypheophorbide (9-HPbD) enhanced cytotoxicity and apoptosis on AMC-HN-3 laryngeal cancer cells. The present study aimed to investigate anti-tumor effect of the combined therapy in vivo and the potential role of reactive oxygen species (ROS) in these enhanced apoptotic pathways initiated by the combined therapy in AMC-HN-3 cells., Methods: Mitochondrial membrane potential (MMP) and intracellular Ca 2+ were detected under confocal microscopy. Various apoptotic pathways were detected by western blots. In vivo study with the combined regimen was also performed on AMC-HN-3 cells-xenograft nude mice., Results: In vitro study showed that the combined treatment could decrease the level of MMP, increase intracellular Ca 2+ and AIF translocation, and activate the expression of caspase-12. Mechanismly, the augmented apoptotic effect was mediated by ROS. The synergistic antitumor effect was also observed in vivo., Conclusions: The mechanism of CBDCA and 9-HPbD-PDT combination involves ROS-mediated mitochondrial and endoplasmic reticulum apoptosis pathways. This combination may be a promising treatment strategy for laryngeal cancer., Competing Interests: Declaration of Competing Interest The authors have declared that no conflicts of interest exist., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The study aimed to develop a method for sublingual administration of 5-aminolevulinic acid to patients and evaluate its effectiveness in fluorescence diagnostics and photodynamic therapy of neoplasms of the oral cavity and larynx., Methods: The boundaries of the neoplasms were established by the video-fluorescence diagnostics and clarified using spectral-fluorescent diagnosis before and after photodynamic therapy., Results: The fluorescence diagnostics demonstrated a high accumulation of protoporphyrin IX, induced by sublingual administration of 5-aminolevulinic acid to patients before the photodynamic therapy and photobleaching of protoporphyrin IX in pathologically altered tissues after the photodynamic therapy. Glucose contained in the sublingual dose supports active transport of 5-ALA into the cells. It increases the PpIX accumulation in the cells, therefore improving the PD and PDT efficacy., Conclusion: The study and the initially obtained results demonstrated the possibility and effectiveness of laser-induced photodiagnostics and photodynamic therapy with sublingual administration of 5-ALA to patients with premalignant lesions of the oral cavity and larynx. It can eliminate the threat of the transformation of these diseases into malignant tumors and prevent the need for surgical treatment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

circRNAs have been shown to be involved in cancer progression. It is unclear whether circPGAM1 exerts its effect on laryngocarcinoma drug resistance. In this study, we employed colony formation and MTT assay to determine colony number and cell viability under cisplatin treatment. TUNEL experiment was used to evaluate apoptosis of laryngocarcinoma cells in the presence of cisplatin. Xenograft tumor experiment was performed to assess in vivo tumor growth of SNU46 cells. We found that circPGAM1 enhanced colony formation and viability of SNU46 and M4E cells. In contrast, circPGAM1 caused attenuated cell apoptosis. Furthermore, we also confirmed that circPGAM1 played a key role in tumor growth in animal model and clinical patients. miR-376a was identified and proved to act as key effector for circPGAM1-mediated drug resistance. Finally, autophagy-related gene ATG2A was shown to rescue miR-376a-modulated drug resistance of laryngocarcinoma cells. Herein, we illuminate the role of circPGAM1 in laryngocarcinoma drug resistance, thereby facilitating development of targeted therapy for treating laryngocarcinoma., Competing Interests: Declaration of competing interest We declare no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To examine the impact of treatment sequences of Immune checkpoint inhibitor (ICI) and cetuximab on clinical outcomes in patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC)., Materials and Methods: Clinicopathologic data were retrospectively collected on patients with R/M HNSCC who received ICI treatment. Association between treatment sequence and clinical outcomes were assessed., Results: A total of 113 patients with R/M HNSCC were analyzed. Patients who had cetuximab prior to ICI had worse overall (HR, 1.83) and progression-free survival (HR, 1.76) compare to those without prior cetuximab. Among patients who had subsequent therapy after ICI, cetuximab-based therapy was associated with a trend toward higher response rate and longer survival than non-cetuximab regimen., Conclusion: Our single institution analysis showed that treatment sequence of cetuximab and ICI in R/M HNSCC may affect clinical outcomes. Cetuximab prior to ICI was associated with worse outcomes while the efficacy of cetuximab may be enhanced after ICI therapy., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

We present a clinical case where a conservative treatment based on photonics [antimicrobial Photodynamic Therapy (aPDT) associated to Photobiomodulation therapy (PBMT)] of a patient with osteoradionecrosis (ORN) due to radiotherapy treatment of a laryngeal cancer. As a result of this combined treatment the ORN was controlled (e.g. the necrosis, infection and suppuration disappeared). Moreover, the symptoms reported by the patient (pain and xerostomia) also diminished along with the repair of oral mucosa. In future cases this combined therapy (e.g. PBM therapy and the aPDT) will be further examined., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: To explore the therapeutic effect of topical 5-Aminolevulinic Acid photodynamic therapy (ALA-PDT) on laryngeal papillomatosis (LP) treatment., Methods: 13 patients with LP underwent topical ALA-PDT after tumor resection (CO 2 laser or/and microdebrider resection). All patients were irradiated 3-4 times. After ALA-PDT treatment, the laryngoscopic examination was performed every 1-2 months to observe the therapeutic effect., Results: All 13 patients were followed up for more than 1 year. Eleven cases (84.6%) showed no recurrence; two cases (15.4%) had relapses. One child developed III° inspiratory dyspnea caused by laryngeal mucosal edema and need endotracheal intubation again. Four patients had adhesion of the anterior commissure of the vocal cord. The detection rate of HPV infections was 76.9% and two patients had multiple HPV subtype co-infection., Conclusions: The preliminary effect of topical ALA-PDT significantly reduces recurrence and improves the cure rate of LP. Further research on this treatment is still required., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: After induction chemotherapy (IC) for laryngeal cancer, Computed Tomography (CT) is used to assess tumor response but lacks rationalized methods for measurement of this response. In T3 laryngeal cancer, remobilization of an initially fixed vocal cord (VC) is a major sign of tumor response. We compared the performances of RECIST1.1, WHO and volumetric methods of evaluating response with laryngeal remobilization to determine if these measurements could objectively assess tumor response., Material and Methods: This monocentric retrospective cohort study included patients treated with T3 laryngeal cancer with initial VC fixation treated with an organ preservation protocol with IC between 1999 and 2012. Tumors were measured with CT using RECIST1.1, WHO and volumetric methods by two radiologists blinded to VC remobilization (VCR), before and after induction chemotherapy and VC mobility was clinically assessed. Radiologic tumor shrinkage was compared to VCR. AUCs of ROC curves were compared. Inter-reader reliability, sensitivity and specificity of optimal cutoffs were determined., Results: Seven females and thirty-six males with a mean age of 59 years were included. AUCs were 0.759, [95%CI 0.614; 0.904] for RECIST1.1, 0.763, [95%CI 0.617; 0.909] for WHO and 0.752, [95%CI 0.608; 0.896] for volumetric evaluations with no significant difference among the three techniques. Inter-reader reader reliabilities were good (RECIST1.1) to excellent (WHO and volumetric methods)., Conclusion: RECIST1.1, WHO and volumetric measures match with VCR after IC in patient with T3 laryngeal cancer. WHO criteria combine accuracy, reproducibility and practical use; they may be best adapted for response assessment and protocol design., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

There is growing evidence that laryngeal cancers are responsive to sex hormones, specifically 17β-estradiol (E 2 ), despite controversy regarding the presence and characterization of E 2 receptors (ER). Determination of sex hormone responsiveness impacts the prognosis of laryngeal cancer patients and the treatment modalities implemented by their clinicians. Discovery of membrane-associated steroid hormone receptors and rapid membrane signaling opened the possibility that cancers previously labeled 'non-hormone dependent' and 'ER negative' might in fact be susceptible to the effects of E 2 via these membrane receptors. ERα66 and ERβ, the classical nuclear receptors, are present in the membranes of different cancer cells via a mechanism referred to as trafficking. Novel splice variants of these traditional receptors, a key example being ERα36, have also been found in the caveolae of cancer cells. Previous work demonstrated that ERα36 has a role in the tumorigenesis of laryngeal cancer, enhancing both proliferation and the anti-apoptotic effect of E 2 against chemotherapeutics. The present study showed that expression of different membrane ERs in laryngeal cancer is not uniform, which may result in differential and even antagonistic responses to E 2 . E 2 had protective or deleterious effects in different cancer cell lines, stimulating proliferation and conferring anti-apoptotic potential to the cancer cells according to their receptor profile. These findings stress the importance of establishing the molecular and clinical characterization of the specific laryngeal tumor in order to tailor treatment accordingly, thus optimizing care while reducing adverse effects for individual patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Laryngeal cancer (LC) remains a challenging disease to treat. The majority of LCs diagnosed worldwide are squamous cell carcinomas (SCC), and current treatment guidelines are designed to address conventional laryngeal SCC. However, several histologically rare tumor types can originate in the larynx. There is a lack of guidelines regarding the best therapeutic approaches to these tumors and their treatment is often modeled after their recommended management at non-laryngeal sites. Understanding the role for systemic therapy in these rare tumors is important, especially for patients with advanced disease or those who are not surgical candidates. We provide in this manuscript a detailed and comprehensive overview of systemic therapy considerations for the following histologic tumor types of the larynx: verrucous carcinoma (VC), HPV-related SCC, basaloid SCC (BSCC), lymphoepithelial carcinoma (LEC), adenosquamous carcinoma (ASC), typical and atypical carcinoid, small cell neuroendocrine carcinoma (SCNC), large cell neuroendocrine carcinoma (LCNC), NUT midline carcinomas (NUTMC), melanoma, adenoid cystic carcinoma, rhabdomyosarcoma (RMS), malignant fibrous histiocytoma (MFH), lymphoma, mucoepidermoid carcinoma (MEC), acinic cell carcinoma, and spindle cell carcinoma (SpCC)., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

In this study, we reported a redox-responsive drug delivery system (DDS) based on heparosan and deoxycholic acid conjugates (HSDs) for effective treatment of laryngopharyngeal carcinoma. The amphiphilic HSDs can self-assemble into stable nanoscale micelles in aqueous medium with favorable drug loading capacity for doxorubicin (DOX). The HSD micelles can exhibit glutathione (GSH)-triggered drug release behavior and reach a nearly 100% release rate in a high GSH level (10 mM) environment. Moreover, FaDu cancer cells can internalize HSD micelles by clathrin-mediated endocytosis, which is energy dependent, fast, and effective. The DOX@HSD induced inhibition of FaDu cancer cells can achieve a minimum of 10-fold selectivity relative to that of COS-7 normal cells. Overall, the redox-responsive DDSs show good biocompatibility and are promising in the clinical treatment of laryngopharyngeal carcinoma., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The optimal treatment for T3 glottic cancers continues to be debated. Organ preservation has become the standard of care, but not all tumors respond equally. The purpose of this was to investigate the long-term survival outcomes of organ preservation protocols based on tumor volume., Methods: A retrospective review of prospectively collected data from 1966 to 2016 was performed. Patients with T3 vocal cord cancer treated with radiation therapy (RT) at the University of Florida were included. Local control rates as well as survival rates were determined with a Kaplan Meier and Cox regression analysis. Survival was analyzed as a function of tumor volume and an optimal cut point was determined., Results: 107/234 patients were included. 79% received RT and 21% chemo-RT. 5-year local control was 61.5% and 5-year disease specific survival was 79.3%. Tumor volume was a significant predictor of survival (p = 0.007). An optimal cut point for tumor volume was 2.5 cc. Patients with tumor volumes ≥2.5 cc had significantly worse (p < 0.05) tumor control rates (100% vs. 70.4%)., Conclusion: Tumor volume is a significant predictor of survival outcomes in T3 vocal cord cancers, but will need external validation. Tumors <2.5 cc have favorable outcomes. Those with higher volume tumors should be counselled appropriately and be considered for primary surgical management., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Photodynamic therapy (PDT) is a minimally invasive therapy used in the treatment of premalignant and malignant diseases, including head and neck carcinomas. It can be applied before or after chemotherapy, irradiation, or surgery. Unlike irradiation and surgery, it can be repeated many times at the same site, and it is also associated with better cosmetic and functional outcomes [1]. We have treated 10 patients with laryngeal carcinomas with PDT since 1998, and herein we describe two such patients who developed vocal cord adhesion due to PDT. To our knowledge, there are no previous reports of patients with glottis atresia due to PDT, thus the cases reported herein are rare, and educationally valuable., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: In patients with head and neck cancer, the management of second primary cancer (SPC) is particularly important for improving survival because of its high incidence and associated mortality. We evaluated the impact of combination chemotherapy on survival and SPC., Method: We retrospectively analyzed data from 49 patients treated with definitive radiation therapy (RT) for T2N0M0 laryngeal squamous cell carcinoma between 2003 and 2011. Among them, 22 patients received combined modality treatment with radiotherapy and S-1 (RT+CT group)., Results: The median follow-up period was 71months (32-111months). A significant difference in overall survival (OS, P<0.01) was observed between the RT+CT group (n=22) and the RT alone group (n=27) though no significant differences were observed in local control and disease specific survival. Univariate analyses showed that an older age (P<0.05) and a higher grade (P<0.05) were associated with OS. Multivariate analysis identified chemotherapy as the most significant predictor of survival (OR, 0.056; 95% CI, 0.008-0.353, P<0.01). A significantly lower incidence of distant metastasis (DM)+SPC (5-year incidence: 5% vs. 19%, P<0.05) and fewer deaths from these causes (1 vs. 8: P<0.05) were observed in the RT+CT group. Multivariate analysis showed that chemotherapy was the most significant factor for the incidence of DM+SPC (OR, 0.074; 95% CI, 0.0065-0.84; P<0.05)., Conclusion: The findings of this study suggest the possibility that combined modality treatment with radiotherapy and S-1 improve survival by preventing distant metastasis and second primary cancer., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Inclusion compounds of photoluminescent hexamolybdenum cluster complexes in the chromium terephthalate metal-organic framework, MIL-101 (MIL, Matérial Institut Lavoisier) were successfully synthesized in two different ways and characterized by means of powder X-Ray diffraction, chemical analysis and nitrogen sorption. Some important functional properties of hexamolybdenum cluster complexes for biological and medical applications, in particular singlet oxygen generation ability, luminescence properties, cellular uptake behavior and cytotoxicity were studied. It was revealed that the inclusion compounds possessed significant singlet oxygen generation activity. The materials obtained showed a low cytotoxicity, thus allowing them to be used in living cells. Confocal microscopy of human larynx carcinoma (Hep-2) cells incubated with the inclusion compounds showed that MIL-101 performed as a nanocarrier adhering to the external cell membrane surface and releasing the cluster complexes which that penetrated into the cells. Moreover, photoinduced generation of reactive oxygen species (ROS) in Hep-2 cells incubated with inclusion compounds was demonstrated. The cluster supported on MIL-101 was shown to possess in vivo phototoxicity., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Intensity-modulated radiotherapy is the gold standard in the treatment of larynx cancers (except T1 glottic tumour). Early T1 and T2 tumours may be treated by exclusive radiation or surgery. For tumours requiring total laryngectomy (T2 or T3), induction chemotherapy followed by exclusive radiotherapy or concurrent chemoradiotherapy is possible. For T4 tumour, surgery must be proposed. The treatment of lymph nodes is based on the initial treatment of the primary tumour. In non-surgical procedure, in case of sequential radiotherapy, the curative dose is 70Gy and the prophylactic dose is 50Gy. An integrated simultaneous boost radiotherapy is allowed (70Gy in 2Gy per fraction and 56Gy in 1.8Gy per fraction or 70Gy in 2.12Gy per fraction). Postoperatively, radiotherapy is used in locally advanced cancer with dose levels based on pathologic criteria (66Gy for R1 resection, 50 to 54Gy for complete resection). Volume delineation was based on guidelines., (Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

There is a lack of data from phase III randomized studies to support an ideal approach for locally advanced oral cavity cancer patients. In general, surgery, radiotherapy and chemotherapy are valid treatment options, and combined approach is usually indicated given poor clinical outcomes with single modality therapy. The aim of this study is to review the current status and future perspectives of induction chemotherapy for locally advanced oral cavity cancer patients., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Xanthohumol (XN), a prenylflavonoid derived from the hop plant (Humulus lupulus L.) has been found to exhibit a broad spectrum of biological properties, including anti-cancer activity. In this study, the mechanisms involved in anti-cancer activity of XN in human RK33 and RK45 larynx cancer cell lines were investigated. The effect of XN on the viability of larynx cancer and normal cells (human skin fibroblasts HSF and rat oligodendroglia-derived cells, OLN-93) was compared. Additionally, the influence of XN on proliferation, cell cycle progression, induction of apoptosis in larynx cancer cells, as well as the molecular mechanisms underlying in these processes were analyzed. XN promoted the reduction of cell viability in cancer cells, but showed low cytotoxicity to normal cells. The decrease in cell viability in the cancer cells was coupled with induction of apoptosis via two pathways. The mechanisms involved in these effects of XN were associated with cell growth inhibition by induction of cell cycle arrest in the G1 phase, increased p53 and p21/WAF1 expression levels, downregulation of cyclin D1 and Bcl-2, and activation of caspases-9, -8, and -3. Moreover, this compound inhibited phosphorylation of ERK1/2, suggesting a key role of the ERKs pathway in the XN-mediated growth suppressing effects against the studied cells. These results indicate that XN could be used as a potential agent for the treatment of patients with larynx cancer., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Natural products are among one of the most promising fields in finding new molecular targets in cancer therapy. Laryngeal carcinoma is one of the most common cancers affecting the head and neck regions, and is associated with high morbidity rate if left untreated. The aim of this study was to examine the antiproliferative effect of Araucaria angustifolia on laryngeal carcinoma HEp-2 cells. The results showed that A. angustifolia extract (AAE) induced a significant cytotoxicity in HEp-2 cells compared to the non-tumor human epithelial (HEK-293) cells, indicating a selective activity of AAE for the cancer cells. A. angustifolia extract was able to increase oxidative damage to lipids and proteins, and the production of nitric oxide, along with the depletion of enzymatic antioxidant defenses (superoxide dismutase and catalase) in the tumor cell line. Moreover, AAE was able to induce DNA damage, nuclear fragmentation and chromatin condensation. A significant increase in the Apoptosis Inducing Factor (AIF), Bax, poly-(ADP-ribose) polymerase (PARP) and caspase-3 cleavage expression were also found. These effects could be related to the ability of AAE to increase the production of reactive oxygen species through inhibition of the mitochondrial electron transport chain complex I activity and ATP production by the tumor cells. The phytochemical analysis of A. angustifolia, performed using High Resolution Mass Spectrometry (HRMS) in MS and MS/MS mode, showed the presence of dodecanoic and hexadecanoic acids, and phenolic compounds, which may be associated with the chemotherapeutic effect observed in this study., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To examine the impact of epidermal growth factor receptor (EGFR) expression level on the efficacy of monoclonal antibodies against the EGFR., Methods: In four human head and neck carcinoma cell lines, epidermal growth factor expression was knocked down by lentiviral RNA interference. Next, the efficacies of cetuximab and panitumumab at concentrations of 4, 40, and 400 μg/ml were measured by real time cell analysis for a 48-h duration. Finally, the different response rates to the drugs were statistically analyzed., Results: The lentiviral EGFR knockdown efficiency ranged from 18 to 54 % across all of the cell lines. All original cell lines exhibited rather poor or inverse responses with regard to EGFR-AB treatment. In contrast, inhibiting EGFR expression in the same cell lines yielded statistically significant better responses to cetuximab or panitumumab treatment., Conclusions: The cell lines used in this study responded poorly to cetuximab and panitumumab. Better anti-EGFR treatment efficacy was related to lower EGFR expression in head and neck cancer cell lines. These findings might influence the selection of patients to receive cetuximab and panitumumab treatment for head and neck cancer., (Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objectives: Head and neck squamous cell carcinomas (HNSCCs) are characterized by marked heterogeneity in their biological behavior and response to treatment. Our goal was the identification of biomarkers that can be used to predict response to chemotherapy in these patients., Materials and Methods: The expression of EGFR, p53, Cyclin D1, p16, p21, p27, p-AKT, HIF-1α, Caspase 3 and BCL2 was analyzed by immunohistochemistry in 41 primary laryngeal/hypopharyngeal squamous cell carcinomas of patients that received induction chemotherapy (cisplatin and 5-fluorouracil) as part of their treatment., Results: Positive expression of p27 and BCL2 had a significant predictive value for chemotherapy response in univariate analysis. The combination of both proteins was not superior in predicting the response to chemotherapy. Furthermore, p27 expression was the only significant predictor of chemotherapy response in multivariate analysis (P=0.015)., Conclusion: p27 Expression may serve as predictive biomarker of response to induction chemotherapy in HNSCC patients., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: Induction chemotherapy (IC) followed by chemoradiation (CRT) for locally advanced squamous cell head and neck cancer (SCCHN) remains controversial in the absence of clear evidence to define its role. As part of a prospective, randomised, multicentre study of CRT for stage III/IV laryngeal/hypopharyngeal cancers (ART DECO, CRUK/10/018), we have examined the attitudes of oncologists in the United Kingdom (UK) to IC., Materials and Methods: Head and neck oncologists across the UK who expressed an interest in participating in the ART DECO trial were asked to complete a short written questionnaire designed to identify current UK practice of IC for stage III-IVb SCCHN. Completed questionnaires were returned to the clinical trials office prior to patient recruitment., Results: Clinicians from twenty-five/48 centres (52.1%) responded. Twenty centres (80%) elected to use IC in the trial. For stage III disease, 80% of centres did not prescribe IC for T1N1 disease and 60% did not offer IC for T3N0 disease. Patients with bulky primary tumours or extensive nodal disease were more likely to receive IC. Thirteen prescribing centres (65%) use 3 drugs (docetaxel, cisplatin, and 5-fluorouracil) compared to 7 (35%) using 2 drugs (cisplatin and 5-fluorouracil). Fifteen centres (75%) prescribed 2 cycles of IC, and 5 (25%) prescribed 3 cycles. There was variation in the dosage for both the 2- and 3-drug regimens., Conclusion: Results suggest that clinical practice in the UK is currently divided between a 2- versus 3-drug regimen for IC for specific subgroups of patients. A consensus regarding the optimal combinations and dosages is required before further optimization of systemic therapy with other cytotoxics and biological agents is attempted., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Inositol polyphosphate 4-phosphatase type II (INPP4B) was recently identified as a tumor resistance factor in laryngeal cancer cells. Herein, we show that INPP4B-mediated resistance is associated with increased glycolytic phenotype. INPP4B expression was induced by hypoxia and irradiation. Intriguingly, overexpression of INPP4B enhanced aerobic glycolysis. Of the glycolysis-regulatory genes, hexokinase 2 (HK2) was mainly regulated by INPP4B and this regulation was mediated through the Akt-mTOR pathway. Notably, codepletion of INPP4B and HK2 markedly sensitized radioresistant laryngeal cancer cells to irradiation or anticancer drug. Moreover, INPP4B was significantly associated with HK2 in human laryngeal cancer tissues. Therefore, these results suggest that INPP4B modulates aerobic glycolysis via HK2 regulation in radioresistant laryngeal cancer cells., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Four water-soluble polysaccharides (LSPa1, LSPb1, LSPb2 and LSPc1) extracted from the fruiting bodies of Lepista sordida were prepared by DEAE cellulose-52 anion-exchange and Sepharose 6 Fast Flow gel-permeation chromatography. LSPa1 was composed of Glc, Man and Gal with a molar ratio of 3.2: 1.3: 0.6. LSPb1, LSPb2 and LSPc1 were composed of Glc, Man, Gal, Rha and Ara in the proportions of 2.6: 2.1: 0.9: 0.6: 0.3, 1.2: 1.0: 2.3: 0.6: 0.5, 0.2: 0.3: 2.3: 0.3: 2.0, respectively. The high-performance gel-permeation chromatography (HPGPC) analysis showed that the average molecular weight (Mw) of four polysaccharides were approximately 156, 134, 96 and 57 kDa, respectively. MTT and lactate dehydrogenase (LDH) assays indicated that three acidic polysaccharides, namely LSPb1, LSPb2 and LSPc1, possessed more potent antiproliferative effect on human laryngocarcinoma Hep-2 cells than neutral polysaccharide LSPa1 in a dose- and time-dependent manner and the effect increased in the order of LSPa1

Objectives: Chemoradiation is the treatment of choice for carcinomas of the pharynx and larynx with imminent loss of organ or function. However, the prognosis after CRT decreases when salvage surgery becomes necessary. Single-cycle induction chemotherapy is therefore performed to identify patients who would benefit more from S than from CRT. The present study aims to evaluate the feasibility and effectiveness of this approach., Materials and Methods: Forty-seven patients received Induction Chemotherapy (IC) with docetaxel plus cisplatin or carboplatin and were subsequently assessed for tumor response. Responders achieving a ≥30% decrease in endoscopic tumor size and a ≥20% decrease in 18F-fluorodeoxyglucose uptake proceeded to primary Chemoradiation (CRT) and non-responders received surgery (S). Six weeks after CRT patients with residual tumors underwent secondary surgery (S)., Results: Thirty eight patients were elected for CRT and 9 received S. A local control rate of 86.1% and disease-free survival of 80.4% was achieved at 2 years. Overall treatment time in CRT-patients >80 days was associated with inferior disease-free survival (p = 0.05), cause-specific survival (p = 0.02), overall survival (p = 0.01) and a trend to inferior local control (p = 0.07) at 2 years., Conclusion: The strategy of selecting patients for CRT vs. S based on the response to IC achieves encouraging rates of disease control by surgery and CRT., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy with neurological disorder which incidence is relatively rare. Since the discovery of the ADAMTS 13 in 1996 and the changes in the treatment (plasma exchanges and rituximab), the prognosis of the TTP has considerably improved. We report the case of a 60-year-old man with a refractory TTP. The subsequent discovery of an epiglottis neoplasia and its treatment saved the patient., (Copyright © 2012. Published by Elsevier SAS.)

Schiff base namely 2-aminomethylthiophenyl-4-bromosalicylaldehyde (ATS)(4-bromo-2-(thiophen-2-yl-imino)methylphenol) and its metal complexes have been synthesized and characterized by elemental analyses, IR, 1H NMR, solid reflectance, magnetic moment, molar conductance, mass spectra, ESR and thermal analysis (TGA). The analytical data of the complexes show the formation of 1:2 [M:L] ratio of the formula [ML2], where M represents Ni(II), Zn(II) and Cu(II) ions, while L represents the deprotonated Schiff base. IR spectra show that ATS is coordinated to the metal ions in a bidentate manner through azomethine-N and phenolic-oxygen groups. The ligand and their metal chelates have been screened for their antimicrobial activities using the disc diffusion method against the selected bacteria. A cytotoxicity of the compounds against colon (HCT116) and larynx (HEP2) cancer cells have been studied. Protonation constants of (ATS) ligand and stability constants of its Cu2+, Co2+, Mn2+, Zn2+ and Ni2+ complexes were determined by potentiometric titration method in 50% (v/v) DMSO-water solution at ionic strength of 0.1 M NaNO3., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Subglottic cancers are extremely rare as a primary malignancy representing <8% of all laryngeal cancers. Typical age at presentation is in the 5th decade. There are three main types of subglottic carcinoma: adenocarcinoma, mucoepidermoid and adenoid cystic carcinoma. We present a rare case of subglottic cancer treated with surgery and adjuvant photodynamic therapy., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Recurrent respiratory papillomatosis (RRP) can be difficult to manage. Symptoms are related to recurrent tracheobronchial papillomas and are usually treated with bronchoscopic removal. Other modalities are added when the papilloma burden becomes too great or recurrence is too frequent, but with limited efficacy. We report a patient with progressive RRP that had become refractory to available therapy. Because papillomas overexpress epidermal growth factor receptor, along with increased expression of cyclooxygenase-2 and prostaglandin E2, it was reasoned that a combination therapy of erlotinib and celecoxib would be effective in controlling papilloma growth. After institutional approval and informed patient consent, this combination was initiated. There was a striking improvement in the number and appearance of respiratory tract papillomas, with elimination of the need for repeated papilloma removal. Pretreatment and posttreatment images document this response, and the improvement has now been maintained for nearly 2 years with effective therapy.

Background: Locally advanced laryngeal and hypopharyngeal cancers (LHC) represent a group of cancers for which surgery, laryngectomy-free survival (LFS), overall survival (OS), and progression-free survival (PFS) are clinically meaningful end points., Patients and Methods: These outcomes were analyzed in the subgroup of assessable LHC patients enrolled in TAX 324, a phase III trial of sequential therapy comparing docetaxel plus cisplatin and fluorouracil (TPF) against cisplatin and fluorouracil (PF), followed by chemoradiotherapy., Results: Among 501 patients enrolled in TAX 324, 166 had LHC (TPF, n = 90; PF, n = 76). Patient characteristics were similar between subgroups. Median OS for TPF was 59 months [95% confidence interval (CI): 31-not reached] versus 24 months (95% CI: 13-42) for PF [hazard ratio (HR) for death: 0.62; 95% CI: 0.41-0.94; P = 0.024]. Median PFS for TPF was 21 months (95% CI: 12-59) versus 11 months (95% CI: 8-14) for PF (HR: 0.66; 95% CI: 0.45-0.97; P = 0.032). Among operable patients (TPF, n = 67; PF, n = 56), LFS was significantly greater with TPF (HR: 0.59; 95% CI: 0.37-0.95; P = 0.030). Three-year LFS with TPF was 52% versus 32% for PF. Fewer TPF patients had surgery (22% versus 42%; P = 0.030)., Conclusions: In locally advanced LHC, sequential therapy with induction TPF significantly improved survival and PFS versus PF. Among operable patients, TPF also significantly improved LFS and PFS. These results support the use of sequential TPF followed by carboplatin chemoradiotherapy as a treatment option for organ preservation or to improve survival in locally advanced LHC.

After radiotherapy with or without chemotherapy differentiation between residual and recurrent head and neck cancer and (chemo)radiation sequelae is often difficult. Currently, most physicians aggressively pursue potential recurrences, leading to a high rate of futile invasive diagnostic, e.g. examinations under general anaesthesia with taking of biopsies, and surgical procedures, e.g. planned neck dissections, and a waste of health care resources. Therefore, diagnostic techniques which reliably select patients who should undergo these procedures are warranted. Conventional imaging techniques are not reliable enough for this purpose. Potential imaging techniques to detect residual and recurrent locoregional disease after chemoradiation are (serial) CT or MRI and FDG-PET, eventually in combination with specific response criteria or scoring systems. Diffusion MRI and PET/CT may further improve these techniques. FDG-PET may help to select patients clinically suspected of recurrent laryngeal carcinoma after radiotherapy for direct laryngoscopy under general anaesthesia. It is not yet clear whether FDG-PET can reliable avoid futile routine evaluation by examination under general anaesthesia in oral and oropharyngeal cancer and planned neck dissection when a residual mass persists in the neck after (chemo)radiation. The most reliable scoring criteria and the optimal time interval between completion of radiation and FDG-PET still has to be assessed.

Angiogenesis or new blood vessel formation is a complex and fundamental event in the process of tumor growth and metastatic dissemination. Actually, most of antiangiogenic agents target the VEGF considered like the most potent proangiogenic factor. These molecules directly inhibit VEGF or the kinase activity of its receptor (VEGFR) and represent a significant therapeutic progress in several solid tumors types. First clinical studies of antiangiogenic agents in thoracic and laryngopharyngeal carcinomas have shown promise mainly in combination with other therapies (chemotherapy, other targeted therapies or radiotherapy). Besides common antiangiogenic therapies-induced adverse events, risks of bleeding caused by tumor necrosis mainly in squamous cell lung carcinomas have been observed during early clinical trials. Assessment of surrogate markers of target inhibition could allow a better selection of patients able to benefit from antiangiogenic treatments eventually combined with chemotherapy or molecules targeting others metabolic pathways.

Background: Randomized trials established chemoradiotherapy as standard treatment for advanced laryngeal cancer. Patients with large-volume T4 disease (LVT4) were excluded from these trials. The purpose of this study was to report T4 laryngeal cancer patient outcome, including those with LVT4 disease, treated with chemoradiotherapy., Patients and Methods: This study is a retrospective subset analysis of 32 patients with T4 laryngeal carcinoma including LVT4 tumors treated on three consecutive protocols investigating paclitaxel (Taxol), 5-fluorouracil, hydroxyurea, and 1.5-Gy twice daily (BID) radiotherapy (TFHX)., Results: Median follow-up is 43 months. Four-year locoregional control (LRC), disease-free survival (DFS), overall survival (OS), and laryngectomy-free survival (LFS) was 71%, 67%, 53%, and 86%, respectively. Four patients required laryngectomy for recurrent or persistent disease. Of disease-free patients with >or=1 year follow-up, 90% demonstrated normal or understandable speech. None required laryngectomy for complications. Among LVT4 patients, 4-year LRC, DFS, OS, and LFS was 71%, 65%, 56%, and 81%, respectively. Induction chemotherapy improved 4-year LRC (90% versus 46%, P = 0.03) and DFS (84% versus 42%, P = 0.03)., Conclusions: Promising control and functional outcomes are achieved with TFHX for T4 laryngeal patients. LVT4 disease had outcomes similar to patients with less advanced disease treated on Radiation Therapy Oncology Group 91-11. Induction chemotherapy improved outcomes, warranting further investigation.

We report a case of 60-year old male who had difficulty in breathing as well as in swallowing. On examination, he was found to be having proliferative growth of epiglottis and right aryepiglottic fold mimicking neoplasm. So emergency tracheostomy was performed and biopsy taken. He was found to be having asymptomatic miliary mottling on routine x-ray chest PA view. Further on HRCT, it turned out to be lesion suggesting tubercular etiology. Histopathology (epiglottic biopsy) report confirmed the whole process as tubercular. The patient recovered promptly in due course with anti-tubercular treatment. Point remains to be seen that if we can avoid tracheostomy and its complications in such cases.

Tumours of the upper aerodigestive tract represent the sixth most frequent kind of cancer in France and throughout the world. If the localised forms may be controlled in the long run in two thirds of cases by surgery or radiotherapy, only one third of locally advanced forms are accessible to a cure after association from radiotherapy and chemotherapy. Besides, with a median of survival less than six months, metastatic tumours present a catastrophic spontaneous prognosis among patients with a medical ground that is often heavily deteriorated by prolonged exposure to alcohol and tobacco. Thus, there is a necessity to implement adapted therapeutic strategies to each patient and based on satisfactory proof levels of effectiveness. Optimisation of existing chemotherapy protocols and development of new therapies, in particular of targeted therapies, remain an important objective in the hope to improve results of treatments in locally advanced and metastatic cancers of the oral cavity.

Historically treatment of head and neck cancers involved surgical resection followed by radiation therapy for advanced tumors. Concurrent chemoradiation therapies have shown equal survival to surgical resection with better preservation of function. However, concurrent therapy does entail significant morbidity, and recent advances have been used to minimize that morbidity. Newer tumor specific medical therapies are anticipated to be less toxic while maintaining a high degree of efficacy. For resectable cancer, transoral laser microsurgery is a new trend in surgery for complete resection of tumors with preservation of function. Advanced reconstructive techniques that allow free transfer of soft tissue and bone from all over the body improve the functional and aesthetic outcomes following major ablative surgery. With successful surgical reconstruction, dental and prosthetic rehabilitation choices are enhanced. Advances in rehabilitation of speech following removal of the larynx have improved the quality of life post-laryngectomy patients. With these newer therapies and methods of reconstruction, each patient needs to be carefully evaluated to maximize the possibility of cure and level of function, and minimize the morbidity associated with treatment. Combined chemotherapy and radiation protocols are associated with increased acute and chronic toxicities that may affect the quality of life due to the impact upon oral disease and oral function. Oral care providers must be aware of advances in cancer management and implications for patient care to effectively care for these patients.

Background: Verrucous carcinoma (VC) of the larynx is a rare variant of well-differentiated squamous cell carcinoma, characterized by locally invasive, exophytic warty growth. The purpose of the present study was to evaluate the experience with this rare disease in Slovenia over a 23-year period and to weigh the potential for cure of different treatment options against the functional outcome., Materials and Methods: The databases of the Cancer Registry of Slovenia as well as of the registries of all three departments licensed for the treatment of laryngeal cancer in the country were used for the identification of patients. Presentation, diagnosis, treatment and outcome were reviewed retrospectively., Results: From 1980 to 2002, 30 patients were diagnosed with VC of the larynx, representing 1.23% of all laryngeal malignancies. The most frequent site of origin was the glottis. Twenty-three patients had surgery (functional 13; total laryngectomy 10), three patients had radiotherapy, and a combination of irradiation and concomitant chemotherapy was used in four patients. Only one tumor recurred, six months after primary radiation treatment, but was successfully salvaged with a total laryngectomy. The 5-year overall survival rate of 75% was not significantly different from an age- and sex-matched cohort from the Slovenian population (P=0.071)., Conclusions: In VC of the larynx, determination of treatment options should be dictated by voice preservation strategies. Surgery remains the gold standard of treatment. However, concomitant radiochemotherapy emerges as an attractive alternative to mutilating surgical procedures.

Neoadjuvant chemotherapies for patients with advanced head and neck squamous cell carcinoma have been widely studied for twenty years. Despite a high level of activity on the primary tumor, no study has demonstrated a survival benefit suggesting the use of neoadjvant chemotherapy. One can consider that the only benefit of such strategy is for larynx preservation in patients with operable hypopharnx or larynx cancer. Nevertheless, recently the well established preservation strategy based on induction chemotherapy following according to the activity by radiotherapy has been knocked over by a strategy developed by Forastiere et al. using primary concomitant chemoradiotherapy. However, the lack of benefit reported by neoadjuvant chemotherapy has been thwarted by the recent results provided by the EORTC study which assessed the survival benefit of neoadjuvant chemotherapy by docetaxel-cisplatin-fluorouracile. Interestingly, since 2002 the clearly established strategies for patients with advanced head and neck cancer have been challenged and new options are emerging. This paper reviews the standard strategy of the past and the future proposal emerging from recent studies.

Resistance to chemotherapy is a common problem encountered in the treatment of head and neck squamous cell carcinoma (HNSCC). Chemoresistant HNSCC tumors frequently overexpress antiapoptotic proteins, such as Bcl-x(L). (-)-gossypol, the negative enantiomer of a cottonseed polyphenol, binds to Bcl-x(L) and was recently been shown to inhibit HNSCC proliferation in vitro. In this study, we assessed the in vivo efficacy of (-)-gossypol in an orthotopic xenograft model of HNSCC, using two human HNSCC cell lines with high Bcl-x(L) expression levels. Both produced tumors in a murine floor-of-mouth model that mimics human HNSCC, exhibiting growth and invasion into adjacent tissues. Mice were randomized into three groups: vehicle control and two daily intraperitoneal (-)-gossypol treatment groups (5 and 15 mg/kg). Tumors were measured twice weekly. In the control group, tumors grew progressively, whereas in (-)-gossypol treatment groups, tumor growth was significantly suppressed. The mitotic rate in tumors from (-)-gossypol-treated animals was significantly lower than that in controls, and an increase in the percentage of apoptotic cells was observed in treated tumors versus controls. Residual tumors remained growth-suppressed for 2 weeks after cessation of (-)-gossypol treatment. Our results demonstrate that (-)-gossypol can inhibit tumor growth in an orthotopic model of aggressive HNSCC.

The photokilling activity of 5-(4-trimethylammoniumphenyl)-10,15,20-tris(2,4,6-trimethoxyphenyl)porphyrin (CP) was evaluated on a Hep-2 human larynx-carcinoma cell line. Cell treatment was carried out with 5 microM CP incorporated into liposomal vesicles. Under violet-blue exciting light, the red fluorescence of CP was mainly detected as a filamentous pattern characteristic of mitochondrial localization. Similar pattern was also observed using rhodamine 123 in Hep-2 cells. No dark cytotoxicity was observed using 5 microM CP concentration and long incubation time (24 h). Using Hoechst-33258 and caspase-3 immunostaining methods, cell cultures treated for 24 h with CP and exposed to light for 7.5 min (27 J/cm2) showed a great amount of apoptotic cells (40%). In contrast, necrotic cells (58%) were observed using the same drug concentration but irradiated for 15 min (54 J/cm2). The results show that CP can induce different mechanisms of cell death depending on irradiation doses in the photodynamic treatments, which makes this agent an interesting sensitizer with potential application in photodynamic tumor therapy.

The aim of this study was to analyse prognostic factors for disease free interval (DFI) and overall survival (OS) among patients with larynx and hypopharynx cancer requiring a total laryngectomy. Three groups of patients were studied according to the type of treatment they received. Fifty-eight patients had total laryngectomy, 71 patients had organ preservation treatment including induction chemotherapy followed by exclusive radiotherapy, 26 patients received induction chemotherapy followed by salvage total laryngectomy. The studied potential prognostic factors were age, gender, performans status, primary tumor localization, T status, N status, tumor volume and tumoral EGFR level (fmol/mg protein). The multivariate analysis showed that both N status and tumor volume were significant for DFI and OS. EGFR level was significant only for patients treated by induction chemotherapy and exclusive radiotherapy (p = 0.05 and 0.05 for DFI and OS length, respectively). Among this group, patients with tumor EGFR levels lower and higher than 100 fmol/mg protein had 53% versus 22% and 51% versus 18% 5-year of DFI and OS rates, respectively (Log rank test: p = 0.001 and 0.0001). EGFR determination appears to be a powerful prognostic parameter for patients treated by induction chemotherapy followed by exclusive radiotherapy. Laryngectomy seems to erase the prognostic impact of EGFR expression. These results profile the use of EGFR targeting therapy for this category of patients.