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I Sverige drabbas 1000 personer varje år av huvud- och halscancer. Rökning är den största enskilda orsaken till denna typ av cancer. Att motivera patienterna till att sluta röka är angeläget då fortsatt rökning har negativ inverkan på behandlings-resultatet samt förvärrar biverkningarna av behandlingen. Syftet med denna studie var att undersöka om patienter med huvud- och halscancer fick information om rökning och rökavvänjning inför och under strålbehandling, vad denna informa-tion innehöll samt att beskriva hur patienten upplevde informationen. Metoden var en intervjustudie som genomfördes på strålbehandlingsavdelningen, UMAS, Malmö. Åtta intervjuer genomfördes och resultatet visade att endast tre informan-ter erhållit information kring rökavvänjning från läkare och onkologisjuksköters-kor på strålbehandlingsavdelningen. Alla informanterna hade berättat för läkarna att de rökte men majoriteten upplevde inte att någon notis tagits vid denna infor-mation. En informant hade bett om hjälp för att sluta röka men avråtts av läkare vilket han upplevde som väldigt negativt. De som fått information kring rökav-vänjning upplevde detta som positivt samt kände att de blivit bekräftade. Majoriteten av informanterna hade velat delta i rökavvänjningsintervention om sådan funnits på kliniken. Det dagliga mötet mellan onkologisjuksköterskor och patienter på en strålbehandlingsavdelning innebär en möjlighet för sjuksköterskan att informera, stödja och bekräfta patienten i en rökavvänjningsintervention. / In Sweden 1000 individuals are diagnosed with head and neck cancer each year. Smoking is the major, single cause of this type of cancer. Motivating the patients to quit smoking is of great importance since smoking during treatment increases risks for treatment failure and increased side effects. The aim of this study was to investigate if patients with head and neck cancer received information about smoking and smoking cessation before and during radiation therapy, the content of the information and to describe patients' experience of the information. The method was an interview study and took place in the Department of radiation therapy, UMAS, Malmö. Eight interviews were carried out and the findings showed that only three respondents had received information of smoking cessa-tion from doctors or oncology nurses in the Department of radiation therapy. All of the respondents had informed the doctor of their smoking habit but the majority experienced that they were left without any response. One respondent had asked for smoking cessation aid but had been recommended not to quit smoking during treatment, which he had experienced as very negative. The patients who had re-ceived smoking cessation information experienced this information positive and felt both confirmed and supported. The majority of the respondents would have liked to participate in a smoking cessation intervention if such was available at the department. The daily meeting between nurses and patients in the Department of radiation therapy means an opportunity to give information, support and to con-firm the patient in a smoking cessation intervention.

Developing a head and neck cancer treatment plan for a candidate of Intensity Modulated Radiation Therapy (IMRT) requires extensive domain knowledge and subjective experience. Therefore, it takes a cancer treatment team at least 2 to 3 days to develop such a plan from scratch. Many times the team may not use a reference plan. Sometimes, to reduce the amount of time taken to generate each treatment plan, these experts recall a patient, whose plan they recently prepared, and who had similar symptoms as the candidate. Using this recalled patient's plan as the starting point, the cancer treatment team modifies it based on the differences in the symptoms of the new candidate and those of the reference patient record. The resultant plan after modification is presented as the new treatment plan for the oncologist to evaluate its suitability for treatment of the candidate. This approach is heavily dependent on the team's choice of the reference patient record. Choosing a starting treatment plan where the patient's symptoms are not the closest to the new candidate implies that more time will be spent modifying the plan than is necessary and the resultant treatment plan may not be the best achievable under the same circumstances given a better starting plan. Therefore, the team's bias in choosing the starting plan may affect the quality of treatment plan that is finally produced for the candidate. This thesis proposes a system that behaves like an un-biased radiotherapy expert - following a similar process and standards as the human experts and which searches the entire IMRT patient database and returns the record (with patient symptoms and treatment plan) for a patient whose symptoms are most similar to the candidate's symptoms. It takes in the new candidate's information (from diagnosis, scans of the tumor and interviews with the candidate), searches the database and prints out a patient record showing another patient's treatment plan as the suggested starting point for generating the new plan. The system uses Case-Based Reasoning (CBR) because it mimics the experts' approach since it makes use of previous successes and shuns reasoning that has failed in the past. This occurs by considering only treatment plans that have been implemented successfully on patients in the hospital archive. For this thesis, CBR is applied using fuzzy IF-THEN rules to search the patient database. Fuzzy logic is used because it can handle imprecise expressions commonly used in natural language to determine the appropriate weight of the patient attributes in the search process. Filtering of patient records based on parameter value ranges is also used to reduce the number of records that have to be compared. The system code developed for this thesis was prepared in Java and C Language Integrated Production System (CLIPS) using the Java Expert System Shell (JESS). This system is part of a bigger expert system that is being prepared by the Intelligent Systems Applications Center (ISAC) for Thomas Jefferson University Hospital, expected to generate a radiotherapy plan for a patient designated for IMRT treatment. Initial results from the developed prototype prove the viability of selecting similar patients using CBR. It is important to note that the overall objective of the project is to build a system that effectively aids decision support by the IMRT team when generating a new treatment plan and not to replace them. The team is expected to use the generated plan as a starting point in determining a new treatment plan. If the generated plan is sufficient, the oncologist and their team will have to check this plan (in their various capacities) against expected standards for quality control before passing it on for implementation. This will save them time in planning and allow them to focus more on the patient's needs hence a higher quality of life for the patient after treatment. / Electrical and Computer Engineering

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. It has commonly been associated with exposure to tobacco-derived carcinogens and alcohol consumption. Pembrolizumab has shown to be effective in the treatment of many types of cancers such as melanoma, non-small cell lung cancer, due to its antiproliferative, immunoregulatory properties. The aim of this study was to investigate the effects of naked Pembrolizumab and Pembrolizumab liposome on the level of DNA damage, gene, and protein expressions in peripheral lymphocytes from HNC patients and compared to the healthy individuals by using the Comet and micronucleus assays. Western blotting and real-time polymerase chain reaction were performed to assess the potential of improving the repair mechanisms after treatment with naked Pembrolizumab and Pembrolizumab liposome. According to the results, Comet assay and micronucleus assay showed a significantly decreased DNA damage in the lymphocytes from HNC patients after being treated with naked Pembrolizumab and pembrolizumab liposome. Furthermore, the results have shown that naked Pembrolizumab and pembrolizumab liposomes (10 μg/ml) greatly decreased the oxidative stress produced by H2O2. Both forms of pembrolizumab have also demonstrated improving the repair mechanisms in lymphocytes from HNC patients by modulating the expression of P53, P21, and Bcl-2 at mRNA and protein levels. This study suggested that Pembrolizumab naked and liposome could have an antioxidant role alongside other actions in the treatment of HNSCC. However, further studies on Cancer cell lines and in vivo observation are required to validate the anticancer potential of pembrolizumab naked with liposome in HNC. / Ministry of Higher Education and Scientific Research, Libya

This thesis investigates the feasibility of utilizing biodegradable polymeric microspheres loaded with the anticancer drug 5-fluorouracil (5FU) and superparamagnetic iron oxide nanoparticles (SPIONs) to magnetically deliver the cancer therapeutic 5FU to a target tumor in the human body. The primary method of material loading consisted of a w/o/w double emulsion mechanism which 1) loads and protects 5FU in the inner water phase consisting of distilled water and polyvinyl alcohol (PVA), 2) dispersed SPIONs in the biodegradable polymeric organic phase consisting of methylene chloride (MeCl2) for eventual magnetic transport, and 3) suspended these w/o emulsion droplets in an outer aqueous phase comprised of water and PVA and then evaporating the solvent by convection. This procedure produced dried double emulsion microspheres below 2 µm in diameter. They were characterized using scanning electron microscopy (SEM), and magnetometry, which demonstrated their size and superparamagnetic properties. The encapsulation efficiency of 5FU into these polymeric microspheres was above 95%. Drug release of 5FU from dried double emulsion microspheres was significant over 63 days in water and phosphate buffered saline (PBS). Drug release was faster at 37 °C compared to room temperature (21 °C). The medium of PBS at pH 7.4 and 5.4 promoted faster release than distilled water at pH 7.0. Release was faster from PLGA than from PLA. Antibiotic potency of 5FU remained effective after drug release and degradation of carrier. Application of these microspheres in future clinical trials may present a noninvasive, low-risk method to treating malign tumors in nonresectable regions while demonstrating more effective results than systemic administration of chemotherapy. This research presents a significant innovation in therapeutic drug delivery technology for nonresectable cancerous tumors, particularly in the head and neck regions.

Yes / Introduction: Evolution of a patient-reported symptom-based risk stratification system to redesign the suspected head and neck cancer (HNC) referral pathway (EVEREST-HN) will use a broad and open approach to the nomenclature and symptomatology. It aims to capture and utilise the patient reported symptoms in a modern way to identify patients’ clinical problems more effectively and risk stratify the patient. Method: The review followed the PRISMA checklist for scoping reviews. A search strategy was carried out using Medline, Embase and Web of Science between January 1st 2012 and October 31st 2023. All titles, abstracts and full paper were screened for eligibility, papers were assessed for inclusion using predetermined criteria. Data was extracted pertaining to the aims, type of study, cancer type, numbers of patients included and symptoms, presenting complaints or signs and symptoms. Results: There were 9,331 publications identified in the searches, following title screening 350 abstracts were reviewed for inclusion and 120 were considered for eligibility for the review. 48 publications met the eligibility criteria and were included in the final review. Data from almost 11,000 HNC patients was included. Twenty-one of the publications were from the UK, most were retrospective examination of patient records. Data was extracted and charted according to the anatomical area of the head and neck where the symptoms are subjectively and objectively found, and presented according to lay terms for symptoms, clinical terms for symptoms and the language of objective clinical findings. Discussion: Symptoms of HNC are common presenting complaints, interpreting these along with clinical history, examination and risk factors will inform a clinician’s decision to refer as suspected cancer. UK Head and Neck specialists believe a different way of triaging the referrals is needed to assess the clinical risk of an undiagnosed HNC. EVEREST-HN aims to achieve this using the patient history of their symptoms. This review has highlighted issues in terms of what is considered a symptom, a presenting complaint and a clinical finding or sign. / National Institute for Health and Care Research Programme Grant for Applied Research NIHR 202862.

Yes / Introduction: Between 2009/2010 and 2019/2020, England witnessed an increase in suspected head and neck cancer (sHNC) referrals from 140 to 404 patients per 100 000 population. 1 in 10 patients are not seen within the 2-week target, contributing to patient anxiety. We will develop a pathway for sHNC referrals, based on the Head and Neck Cancer Risk Calculator. The evolution of a patient-reported symptom-based risk stratification system to redesign the sHNC referral pathway (EVEREST-HN) Programme comprises six work packages (WPs). This protocol describes WP1 and WP2. WP1 will obtain an understanding of language to optimise the SYmptom iNput Clinical (SYNC) system patient-reported symptom questionnaire for sHNC referrals and outline requirements for the SYNC system. WP2 will codesign key elements of the SYNC system, including the SYNC Questionnaire, and accompanying behaviour change materials. Methods and analysis: WP1 will be conducted at three acute National Health Service (NHS) trusts with variation in service delivery models and ensuring a broad mixture of social, economic and cultural backgrounds of participants. Up to 150 patients with sHNC (n=50 per site) and 15 clinicians (n=5 per site) will be recruited. WP1 will use qualitative methods including interviews, observation and recordings of consultations. Rapid qualitative analysis and inductive thematic analysis will be used to analyse the data. WP2 will recruit lay patient representatives to participate in online focus groups (n=8 per focus group), think-aloud technique and experience-based codesign and will be analysed using qualitative and quantitative approaches. Ethics and dissemination: The committee for clinical research at The Royal Marsden, a research ethics committee and the Health Research Authority approved this protocol. All participants will give informed consent. Ethical issues of working with patients on an urgent cancer diagnostic pathway have been considered. Findings will be disseminated via journal publications, conference presentations and public engagement activities. / This work was supported by NIHR Programme Grants for Applied Research (grant number: NIHR202862).

Yes / The chemokine receptor CCR7 is expressed on lymphocytes and dendritic cells and is responsible for trafficking of these cells in and out of secondary lymphoid organs. It has recently been shown that CCR7 expression is elevated in a number of cancers, including head and neck cancers, and that its expression correlates to lymph node (LN) metastasis. However, little is known about the factors that can induce CCR7 expression in head and neck cancers. We compared the protein expression and functional responses of CCR7 under normoxia and hypoxia in head and neck cancer cell lines OSC-19, FaDu, SCC-4, A-253 and Detroit-562 cultured as monolayers, spheroids, and grown in vivo as xenografts in balb/c mice. In addition, we analysed the correlation between hypoxia marker HIF-1α and CCR7 expression in a tissue microarray comprising 80 clinical samples with various stages and grades of malignant tumour and normal tissue. Under hypoxia, the expression of CCR7 is elevated in both in vitro and in vivo models. Furthermore, in malignant tissue, a correlation is observed between hypoxia marker HIF-1α and CCR7 across all clinical stages. This correlation is also strong in early histological grade of tumours. Hypoxia plays a role in the regulation of the expression of CCR7 and it may contribute to the development of a metastatic phenotype in head and neck cancers through this axis.

We aimed to evaluate possible factors influencing the long-term survival of teeth after tumor therapy to the head and neck region with and without radiation. Between January 2019 and January 2020, patients who underwent for head and neck cancer and received dental treatment before and after at the Department of Prosthetic Dentistry of the Martin Luther University Halle- Wittenberg were enrolled in the study. Clinical examination with assessment of dental status and stimulated salivary flow rate (SFR) was performed and information about disease progression and therapy was retrieved from medical records. Of 118 patients (male: 70.3%; mean age: 63.2 12.4 years), 95 received radiotherapy (RT), and 47 were administered radio-chemotherapy (RCT). The teeth of irradiated patients exhibited a lower 5-year survival probability (74.2%) than those of nonirradiated patients (89.4%). The risk of loss (RL) after RT increased with nicotine use, presence of intraoral defects, reduced SFR, RCT and regarding mandibular teeth, and decreased with crowning following. Lower SFR increased the RL even without RT. Consideration of patient’s treatment history, individual risk profile, and clinical findings during the prosthetic planning phase could enable earlier, more targeted dental treatment after (e.g., timely crowning).