Skull base surgery for malignant tumors: The 2nd international collaborative study (1995-2015).

BACKGROUND: The current study presents the effort of a global collaborative group to review the management and outcomes of malignant tumors of the skull base worldwide. PATIENTS AND METHODS: A total of 28 institutions contributed data on 3061 patients. Analysis evaluated clinical variables, survival outcomes, and multivariable factors associated with outcomes. RESULTS: The median age was 56 years (IQR 44-67). The open surgical approach was used in 55% (n = 1680) of cases, endoscopic resection was performed in 36% (n = 1087), and the combined approach in 9.6% (n = 294). With a median follow-up of 7.1 years, the 5-year OS DSS and RFS were 65%, 71.7% and 53%, respectively. On multivariable analysis, older age, comorbidities, histology, dural/intracranial involvement, positive margins, advanced stage, and primary site were independent prognostic factors for OS, DSS, and RFS. Adjuvant RT was a protective prognostic factor. CONCLUSION: The progress across various disciplines may have contributed to improved OS and DSS in this study compared to previous reports.

Is ChatGPT accurate and reliable in answering questions regarding head and neck cancer?

Background and objective: Chat Generative Pre-trained Transformer (ChatGPT) is an artificial intelligence (AI)-based language processing model using deep learning to create human-like text dialogue. It has been a popular source of information covering vast number of topics including medicine. Patient education in head and neck cancer (HNC) is crucial to enhance the understanding of patients about their medical condition, diagnosis, and treatment options. Therefore, this study aims to examine the accuracy and reliability of ChatGPT in answering questions regarding HNC. Methods: 154 head and neck cancer-related questions were compiled from sources including professional societies, institutions, patient support groups, and social media. These questions were categorized into topics like basic knowledge, diagnosis, treatment, recovery, operative risks, complications, follow-up, and cancer prevention. ChatGPT was queried with each question, and two experienced head and neck surgeons assessed each response independently for accuracy and reproducibility. Responses were rated on a scale: (1) comprehensive/correct, (2) incomplete/partially correct, (3) a mix of accurate and inaccurate/misleading, and (4) completely inaccurate/irrelevant. Discrepancies in grading were resolved by a third reviewer. Reproducibility was evaluated by repeating questions and analyzing grading consistency. Results: ChatGPT yielded "comprehensive/correct" responses to 133/154 (86.4%) of the questions whereas, rates of "incomplete/partially correct" and "mixed with accurate and inaccurate data/misleading" responses were 11% and 2.6%, respectively. There were no "completely inaccurate/irrelevant" responses. According to category, the model provided "comprehensive/correct" answers to 80.6% of questions regarding "basic knowledge", 92.6% related to "diagnosis", 88.9% related to "treatment", 80% related to "recovery - operative risks - complications - follow-up", 100% related to "cancer prevention" and 92.9% related to "other". There was not any significant difference between the categories regarding the grades of ChatGPT responses (p=0.88). The rate of reproducibility was 94.1% (145 of 154 questions). Conclusion: ChatGPT generated substantially accurate and reproducible information to diverse medical queries related to HNC. Despite its limitations, it can be a useful source of information for both patients and medical professionals. With further developments in the model, ChatGPT can also play a crucial role in clinical decision support to provide the clinicians with up-to-date information.

European Head and Neck Society recommendations for head and neck cancer survivorship care.

Survivors of head and neck cancer can experience long-term consequences of the cancer and subsequent treatments even after the cancer has resolved. Increasingly clinicians are aware of the social, psychological, financial, and emotional impacts of these cancers, in addition to the support required for the physical symptoms. This review provides recommendations on the long-term management and support required for survivors of head and neck cancer in the European healthcare setting.

Human laryngeal squamous cell carcinoma cell line release of endogenous anandamide and 2-arachidonoylglycerol, and their antiproliferative effect via exogenous supplementation: an in vitro study.

The level of the major endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are altered in several types of carcinomas, and are known to regulate tumor growth. Thusly, this study hypothesized that the HEp-2 human laryngeal squamous cell carcinoma (LSCC) cell line releases AEA and 2-AG, and aimed to determine if their exogenous supplementation has an anti-proliferative effect in vitro. In this in vitro observational study a commercial human LSCC cell line (HEp-2) was used to test for endogenous AEA and 2-AG release via liquid chromatography-tandem mass spectrometry (LC-MS/MS). The anti-proliferative effect of AEA and 2-AG supplementation was evaluated via WST-1 proliferation assay. It was observed that the HEp-2 LSCC cell line released AEA and 2-AG; the median quantity of AEA released was 15.69 ng mL-1 (range: 14.55-15.95 ng mL-1) and the median quantity of 2-AG released was 2.72 ng -1 (range: 2.67-2.74 ng mL-1). Additionally, both AEA and 2-AG exhibited an anti-proliferative effect. The anti-proliferative effect of 2-AG was stronger than that of AEA. These findings suggest that AEA might function via a CB1 receptor-independent pathway and that 2-AG might function via a CB2-dependent pathway. The present findings show that the HEp-2 LSCC cell line releases the major endocannabinoids AEA and 2-AG, and that their supplementation inhibits tumor cell proliferation in vitro. Thus, cannabinoid ligands might represent novel drug candidates for laryngeal cancers, although functional in vivo studies are required in order to validate their potency.

A European survey on the practice of nutritional interventions in head-neck cancer patients undergoing curative treatment with radio(chemo)therapy.

PURPOSE: As the practice of nutritional support in patients with head and neck cancer (HNC) during curative radio(chemo)therapy is quite heterogeneous, we carried out a survey among European specialists. METHODS: A 19-item questionnaire was drawn up and disseminated via the web by European scientific societies involved in HNC and nutrition. RESULTS: Among 220 responses, the first choice was always for the enteral route; naso-enteral tube feeding was preferred to gastrostomy in the short term, while the opposite for period longer than 1 month. Indications were not solely related to the patient's nutritional status, but also to the potential burden of the therapy. CONCLUSION: European HNC specialists contextualize the use of the nutritional support in a comprehensive plan of therapy. There is still uncertainty relating to the role of naso-enteral feeding versus gastrostomy feeding in patients requiring < 1 month nutritional support, an issue that should be further investigated.

Development and validation of an improved classification and risk stratification system for carotid body tumors: Multinational collaborative cohort study.

BACKGROUND: This study aims to develop and validate a new classification system that better predicts combined risk of neurological and neurovascular complications following CBT surgery, crucial for treatment decision-making. METHODS: Multinational retrospective cohort study with 199 consecutive cases. A cohort of 132 CBT cases was used to develop the new classification. To undertake external validation, assessment was made between the actual complication rate and predicted risk by the model on an independent cohort (n = 67). RESULTS: Univariate analyses showed statistically significant associations between developing a complication and the following factors: craniocaudal dimension, volume, Shamblin classification, and Mehanna types. In the multivariate prognostic model, only Mehanna type remained as a significant risk predictor. The risk of developing complications increases with increasing Mehanna type. CONCLUSIONS: We have developed and then validated a new classification and risk stratification system for CBTs, which demonstrated better prognostic power for the risk of developing neurovascular complications after surgery.

European white paper: oropharyngeal dysphagia in head and neck cancer.

PURPOSE: To develop a European White Paper document on oropharyngeal dysphagia (OD) in head and neck cancer (HNC). There are wide variations in the management of OD associated with HNC across Europe. METHODS: Experts in the management of specific aspects of OD in HNC across Europe were delegated by their professional medical and multidisciplinary societies to contribute to this document. Evidence is based on systematic reviews, consensus-based position statements, and expert opinion. RESULTS: Twenty-four sections on HNC-specific OD topics. CONCLUSION: This European White Paper summarizes current best practice on management of OD in HNC, providing recommendations to support patients and health professionals. The body of literature and its level of evidence on diagnostics and treatment for OD in HNC remain poor. This is in the context of an expected increase in the prevalence of OD due to HNC in the near future. Contributing factors to increased prevalence include aging of our European population (including HNC patients) and an increase in human papillomavirus (HPV) related cancer, despite the introduction of HPV vaccination in various countries. We recommend timely implementation of OD screening in HNC patients while emphasizing the need for robust scientific research on the treatment of OD in HNC. Meanwhile, its management remains a challenge for European professional associations and policymakers.

Recommendations for head and neck surgical oncology practice in a setting of acute severe resource constraint during the COVID-19 pandemic: an international consensus.

The speed and scale of the global COVID-19 pandemic has resulted in unprecedented pressures on health services worldwide, requiring new methods of service delivery during the health crisis. In the setting of severe resource constraint and high risk of infection to patients and clinicians, there is an urgent need to identify consensus statements on head and neck surgical oncology practice. We completed a modified Delphi consensus process of three rounds with 40 international experts in head and neck cancer surgical, radiation, and medical oncology, representing 35 international professional societies and national clinical trial groups. Endorsed by 39 societies and professional bodies, these consensus practice recommendations aim to decrease inconsistency of practice, reduce uncertainty in care, and provide reassurance for clinicians worldwide for head and neck surgical oncology in the context of the COVID-19 pandemic and in the setting of acute severe resource constraint and high risk of infection to patients and staff.

Human papillomavirus infection in patients with laryngeal carcinoma.

BACKGROUND: The aim of this study was to determine the HPV positivity rate in patients with laryngeal cancer, and to determine the effect of HPV positivity on survival. An additional aim was to determine if patients with HPV positive laryngeal cancer are more sensitive to chemotherapy and if such sensitivity differs according to chemotherapy protocol. METHODS: The study included laryngeal specimens obtained from 82 laryngeal cancer patients and 11 laryngeal specimens with normal laryngeal mucosa that were obtained from our hospital's paraffin block archives between 1995 and 2013. HPV was detected via chromogenic in situ hybridization (cISH) and confirmed via genotyping. RESULTS: HPV was not detected in any of the 82 laryngeal cancer patients' laryngeal specimens, nor in any of the 11 archived laryngeal specimens with normal laryngeal mucosa via cISH. Genotyping confirmed these findings; none of the HPV types studied were detected in any of the specimens. As none of the study samples were HPV positive, it was not possible to compare survival, recurrence, or chemotherapy sensitivity. CONCLUSIONS: HPV infection is not a leading cause of laryngeal cancer; however, additional research on HPV positivity in patients with laryngeal cancer and its effect on recurrence, survival, and chemotherapy sensitivity is warranted.

High daily fraction dose external radiotherapy for T1 glottic carcinoma: treatment results and prognostic factors.

BACKGROUND: The purpose of this study was to investigate the prognostic factors and treatment results of T1N0M0 glottic laryngeal carcinoma irradiated with 2.3 Gray (Gy) per fraction. METHODS: A total of 183 patients with glottic carcinoma treated between June 1998 and January 2007 were retrospectively evaluated. Of the 183 patients, 163 patients (89%) had T1a and 20 patients (11%) had T1b disease. All patients received 2.3 Gy per fraction to a median total dose of 64.4 Gy. RESULTS: The median follow-up was 63 months. The 5-year overall survival (OS), local control, and cancer-specific survival rates were 89%, 81%, and 90%, respectively. Multivariate analysis showed overall treatment time and age to be significant prognostic factors for local control and OS. We observed no grade IV or grade V acute toxicity. Trachea-esophageal fistula as late toxicity was observed in only 1 patient. CONCLUSIONS: High daily fraction scheme seems to be a feasible schedule for early glottic carcinomas.

A retrospective comparison of robotic stereotactic body radiotherapy and three-dimensional conformal radiotherapy for the reirradiation of locally recurrent nasopharyngeal carcinoma.

PURPOSE: We assessed therapeutic outcomes of reirradiation with robotic stereotactic radiotherapy (SBRT) for locally recurrent nasopharyngeal carcinoma (LRNPC) patients and compared those results with three-dimensional conformal radiotherapy (CRT) with or without brachytherapy (BRT). METHODS AND MATERIALS: Treatment outcomes were evaluated retrospectively in 51 LRNPC patients receiving either robotic SBRT (24 patients) or CRT with or without BRT (27 patients) in our department. CRT was delivered with a 6-MV linear accelerator, and a median total reirradiation dose of 57 Gy in 2 Gy/day was given. Robotic SBRT was delivered with CyberKnife (Accuray, Sunnyvale, CA). Patients in the SBRT arm received 30 Gy over 5 consecutive days. We calculated actuarial local control and cancer-specific survival rates for the comparison of treatment outcomes in SBRT and CRT arms. The Common Terminology Criteria for Adverse Events v3.0 was used for toxicity evaluation. RESULTS: The median follow-up was 24 months for all patients. Two-year actuarial local control rates were 82% and 80% for SBRT and CRT arms, respectively (p = 0.6). Two-year cancer-specific survival rates were 64% and 47% for the SBRT and CRT arms, respectively (p = 0.4). Serious late toxicities (Grade 3 and above) were observed in 21% of patients in the SBRT arm, whereas 48% of patients had serious toxicity in the CRT arm (p = 0.04). Fatal complications occurred in three patients (12.5%) of the SBRT arm, and four patients (14.8%) of the CRT arm (p = 0.8). T stage at recurrence was the only independent predictor for local control and survival. CONCLUSION: Our robotic SBRT protocol seems to be feasible and less toxic in terms of late effects compared with CRT arm for the reirradiation of LRNPC patients.

Salvage reirradiaton with stereotactic body radiotherapy for locally recurrent head-and-neck tumors.

PURPOSE: In this study, we present our results of reirradiation of locally recurrent head-and-neck cancer with image-guided, fractionated, frameless stereotactic body radiotherapy technique. METHODS AND MATERIALS: From July 2007 to February 2009, 46 patients were treated using the CyberKnife (Accuray, Sunnyvale, CA) at the Department of Radiation Oncology, Hacettepe University, Ankara, Turkey. All patients had recurrent, unresectable, and previously irradiated head-and-neck cancer. The most prominent site was the nasopharynx (32.6%), and the most common histopathology was epidermoid carcinoma. The planning target volume was defined as the gross tumor volume identified on magnetic resonance imaging and computed tomography. There were 22 female and 24 male patients. Median age was 53 years (range, 19-87 years). The median tumor dose with stereotactic body radiotherapy was 30 Gy (range, 18-35 Gy) in a median of five (range, one to five) fractions. RESULTS: Of 37 patients whose response to therapy was evaluated, 10 patients (27%) had complete tumor regression, 11 (29.8%) had partial response, and 10 (27%) had stable disease. Ultimate local disease control was achieved in 31 patients (83.8%). The overall survival was 11.93 months in median (ranged, 11.4-17.4 months), and the median progression free survival was 10.5 months. One-year progression-free survival and overall survival were 41% and 46%, respectively. Grade II or greater long-term complications were observed in 6 (13.3%) patients. On follow-up, 8 (17.3%) patients had carotid blow-out syndrome, and 7 (15.2%) patients died of bleeding from carotid arteries. We discovered that this fatal syndrome occurred only in patients with tumor surrounding carotid arteries and carotid arteries receiving all prescribed dose. CONCLUSIONS: Stereotactic body radiotherapy is an appealing treatment option for patients with recurrent head-and-neck cancer previously treated with radiation to high doses. Good local control with considerable 1-year survival is achieved with a relatively high rate of morbidity and related mortality.

Post-operative radiotherapy in advanced laryngeal cancer: effect on local and regional recurrence, distant metastases and second primaries.

This was a retrospective study of patients who did or did not receive post-operative radiotherapy for squamous cell carcinoma of the larynx.The rates of local and regional recurrences, distant metastases and second primaries were evaluated in 236 patients who received radiotherapy following surgery. These rates were evaluated and compared with those from 294 patients treated with surgery alone. Multivariate analysis of irradiated patients revealed that local and regional recurrences were determined independently by tumour (T) and pathologic node (pN) stages (p < 0.05). The distant metastasis rate significantly depended on N stage (p < 0.05). Multiple primary tumours were not significantly affected by any of the factors studied (p > 0.05). Analysis of both irradiated and non-irradiated patients revealed that local and regional recurrence was determined independently by pathologic T (pT) stage, tumour localization, radiation status and pN stages (p < 0.05). The distant metastasis rate significantly depended on N stage and tumour localization (p < 0.05) and the rate of formation of multiple primary tumours was significantly affected by the patient's age and radiation status (p < 0.05). In conclusion irradiation of laryngeal cancer patients independently increases the risk of local and regional recurrence, and also increases the risk of multiple primary tumours while not significantly influencing the risk of distant metastasis. The risk of distant metastasis is affected by determinants of advanced lesions and tumour localization.

Hypopharyngeal squamous cell carcinoma in a child.

Squamous cell carcinoma of the hypopharynx is extremely rare in children. We present a 13-year-old girl with squamous cell carcinoma of the hypopharynx whose father was a coal-miner and a heavy smoker.

Induction chemotherapy with cisplatin and 5-fluorouracil followed by chemoradiotherapy or radiotherapy alone in the treatment of locoregionally advanced resectable cancers of the larynx and hypopharynx: results of single-center study of 45 patients.

BACKGROUND: Induction chemotherapy with cisplatin and fluorouracil and radiotherapy is an effective alternative to surgery in patients with carcinoma of the larynx and hypopharynx who are treated for organ preservation. METHODS: We designed a protocol to evaluate the possibility of organ preservation in patients with advanced, resectable carcinoma of the larynx and hypopharynx. Forty-five eligible patients who were followed up between April 1999 and May 2001 were enrolled. Initially, these patients were treated with two cycles of induction chemotherapy consisting of cisplatin, 20 mg/m2/day on days 1 to 5, and 5-fluorouracil, 600 mg/m2/day by continuous infusion on days 1 to 5. Patients who had a complete response to chemotherapy were treated with definitive radiotherapy; patients who had a partial response to chemotherapy were treated with chemoradiotherapy. Cisplatin, 35 mg/m2/week, was introduced throughout the duration of radiotherapy. Patients who had no response or progressive disease underwent surgery with postoperative radiotherapy. Patients with N2 or N3 positive lymph nodes underwent neck dissection after the treatment. RESULTS: The mean age was 56.6 years (range, 34-75 years). The overall response rate to induction chemotherapy was 71.1%, with a 17.8% complete response rate and 53.3% partial response rate. With a median follow-up of 13.7 months, 23 (51.1%) of all patients and 63.3% of surviving patients have had a preservation of the larynx or hypopharynx and remain disease free. The most common toxicities were nausea and vomiting and mucositis. CONCLUSION: Organ preservation, with multimodality treatment, may be achievable in some of the patients with resectable, advanced larynx or hypopharynx cancers without apparent compromise of survival.

Immunohistochemical Localization of p53 in Human Thyroid Neoplasms: Correlation with Biological Behavior.

Molecular analyses of thyroid tumors have documented mutations in the tumor suppressor p53 gene almost exclusively in anaplastic carcinomas. In contrast, immunohistochemistry has localized p53 in differentiated papillary and follicular thyroid cancers. To establish the significance of p53 immunolocalization in these lesions, 78 thyroid tumors of follicular derivation were examined. All tumors were classified by strict criteria and the extent of tumor was determined morphologically. Immunohistochemical staining for p53 was performed on paraffin sections of formalin-fixed tumor tissue. The results of staining were correlated with diagnosis, tumor extent and clinical outcome. Immunopositivity for p53 was diffuse and strong in all five anaplastic carcinomas examined. There was no staining in five of six follicular adenomas. Four of nine follicular carcinomas had some degree of nuclear staining, but this was focal; all nine tumors were confined to the thyroid at the time of examination. Of 49 papillary carcinomas, 26 were intrathyroidal, and 7 of these were occult; there was no p53 positivity in any occult lesion and only S of the 19 palpable lesions stained. In contrast, among 23 papillary carcinomas with extra thyroidal extension or metastases, only 9 were negative for p53 immunoreactivity. Five of seven tall cell papillary carcinomas and one of two insular carcinomas had p53 immunopositivity and this correlated with aggressive behavior. These results support the tumorigenic role of p53 mutations postulated for anaplastic thyroid carcinomas and indicate that localization of p53 by immunohistochemistry is a useful prognostic index of clinical behavior in differentiated thyroid carcinomas of follicular cell derivation.