ABSTRACT Background Because salivary gland cancers (SGC) are rare and include different tumor subtypes, data on their long‐term quality of life and late toxicities are sparse. Methods Multi‐national study including SGC survivors more than 5 years after diagnosis. They completed the European Organisation for Research and Treatment of Cancer (EORTC) quality of life core questionnaire together with its head and neck cancer module and reported problems that were most bothering for them. Toxicity was clinically assessed. Results Altogether, 60 survivors from nine countries participated and reported dry mouth (mean score 37.2), use of painkillers (35.0), problems with sexuality (30.1), insomnia (28.9), fatigue (27.8), trismus (24.9), and sticky saliva (23.3). The most frequently mentioned long‐term problem was dry mouth , mentioned by a third of all participants. The most frequent toxicities were hearing impairment , soft tissue fibrosis , dry mouth , and cranial neuropathies . Conclusions Dry mouth is a frequent and disturbing problem in SGC survivors.

Our aim was to investigate oral health-related quality of life (OHRQoL) and toxicities in long-term head and neck cancer (HNC) survivors diagnosed ≥five years earlier. HNC survivors treated between 2007 and 2013 participated in an international cross-sectional study. They completed the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (EORTC QLQ-C30) and the oral health module (EORTC QLQ-OH15) and attended a hospital examination. Clinicians scored toxicities using the Common Terminology Criteria for Adverse Events version 5.0. OHRQoL was analyzed based on four types of treatment: surgery, radiotherapy, chemoradiotherapy without surgery and surgery with postoperative (chemo) radiotherapy. Survivors were divided into three groups according to the EORTC QLQ-OH15 oral health-QoL scale score; the lowest (defined as poor OHRQoL), middle and highest tertile. Eleven sites in six countries enrolled 404 HNC survivors. The median time since diagnosis was 8.4 years, the mean age was 66 years and 67

INTRODUCTION:Minimal important change estimates (MIC) are useful for interpreting results of clinical research with quality of life (QoL) as an endpoint. For the European Organisation for Research and Treatment of Cancer head and neck cancer module, the EORTC QLQ-HN43, no such thresholds are established. METHODS:Head and neck cancer patients under active treatment (n = 503) from 15 countries completed the EORTC QLQ-HN43 three times (t1: before treatment, t2: three months after t1, t3: six months after t1). A subgroup completed a Subjective Significance Questionnaire (SSQ), indicating experienced change from the previous time point in four QoL domains. QoL was assumed to deteriorate after t1 and improve again until t3. The MIC was established using the average of mean differences in SSQ groups (MICmean) and estimates based on logistic regressions (MICpredict). Additionally, minimal detectable changes (MDC) were computed using 0.5 standard deviation and standard error of the mean. RESULTS:For swallowing, speech, dry mouth, and global QoL, the MIC for deterioration were 13, 14, 26, and 10 respectively. The MIC for improvement were 8 (swallowing), 6 (dry mouth), and 5 (global QoL); no MIC for speech improvement can be presented because of insufficient correlation between change score and anchor. The MDC estimates for deterioration were 15, 14, 15, and 11. For improvement, the MDC estimates were 13, 14, 14, and 11. CONCLUSIONS:Our results underline that no single MIC or MDC can be applied to all EORTC QLQ-HN43 scales, and that the MIC for deterioration seems larger than those for improvement.

Vefir í munni geta orðið fyrir breytingum eða skaða vegna sjúkdóma sem hafa aðallega áhrif á önnur líkamskerfi. Einkenni slíkra altækra sjúkdóma sem birtast í munni geta verið afar breytileg bæði hvað varðar tíðni og birtingarmynd. Einkenni altækra sjúkdóma sem birtast í munni geta verið fyrstu einkenni bráðra eða langvinnra sjúkdóma og geta hafist mörgum árum áður en altæk einkenni koma fram og sjúkdómur greinist.Einnig geta sjúklegar breytingar í munnslímhúð, kjálkum og aðliggjandi svæðum haft áhrif á almennt heilbrigði sjúklings.Vaxandi lífslíkur og framfarir í heilbrigðisþjónustu valda því að líklegt er að fjöldi einstaklinga með einkenni altækra sjúkdóma sem birtast í munni muni aukast jafnt og þétt. Mikilvægt er að bregðast hratt og vel við hugsanlegum einkennum altækra sjúkdóma sem birtast í munni til að auka lífsgæði sjúklinga.Einkenni í munni geta verið fyrstu merki um undirliggjandi altækan sjúkdóm og geta fylgt eða verið undanfari sjúkdómsgreiningar. Tannlæknar gegna því mikilvægu hlutverki við greiningu og tilvísun sjúklinga með hugsanlega altæka sjúkdóma.Ef kviðverkir, niðurgangur og einkenni frá meltingarvegi fylgja einkennum í munni ætti tannlæknir að vísa sjúklingi tafarlaust áfram til nánari læknisrannsóknar. Mikilvægt er að tannlæknir fylgi meðferð sjúklings eftir í samvinnu við lækni þar sem versnun einkenna í munni getur bent til aukinnar sjúkdómsvirkni. Lykilorð: Munnur, altækur, sjúkdómar, einkenni

Headlines Oral manifestations may be the first sign of a systemic condition or disease Clinical recognition of oral manifestations related to systemic diseases may be difficult and can delay diagnosis Oral conditions related to the treatment of systemic diseases are clinically important to recognize Oral health personnel should be educated to be able to identify and diagnose and manage oral manifestations of systemic diseases and conditions in a timely manner

Treatment-and medication-related side effects can affect the oral cavity and occur for both benign and malignant conditions.Immunocompromised individuals are predisposed to oral infections because the immune system plays a specialized role in host defense.Defects in specific functions of the immune system lead to increased susceptibility to specific pathogens.In this article, we address the impact of osteonecrosis of the jaw, osteoradionecrosis, treatment with monoclonal antibodies, chronic graft versus host disease, and viral infections.All these factors are of importance, especially in cancer treatment and/or allogeneic stem cell transplantation. Treatment-related oral side effects and diseases Osteonecrosis of the jaw (ONJ)Osteonecrosis of the jaw (ONJ) is a rare but serious condition characterized by parts of the jawbone becoming necrotic and infected.The two most common causes of ONJ are related to antiresorptive medications, i.e., bisphosphonates, denosumab and antiangiogenic agents (designated medication-related osteonecrosis of the jaw, MRONJ), and radiotherapy involving the jawbone (designated osteoradionecrosis, ORN). Medication-related osteonecrosis of the jaw (MRONJ)The first reports of MRONJ were published in the beginning of 2000 after the introduction and approval of a new class of nitrogen-containing bisphosphonates for the prevention of bone complications in adults with advanced cancer (1, 2).Bisphosphonates are a class of inorganic drugs with various chemical structures.Bisphosphonates bind to the bone surface and accumulate in the bone where they are released by osteoclasts.In 2011, treatment with a monoclonal antibody, denosumab, was approved for the same indications (3).Denosumab is an inhibitor of RANKL (receptor activator of nuclear factor kappa-B ligand) and inhibits the maturation of

Headlines The nature of the diseases that oral medicine specialists diagnose and manage throughout the oral and maxillofacial region are diverse and closely related to other dental and medical specialties. This relatively young area of dentistry has expanded globally during the past decade as an independent discipline with postgraduate qualifying programmes being offered in several countries, as well as an increasing research community. With a growing proportion of elderly individuals in the population in general across the world, morbidity is likely to increase in terms of both general diseases and conditions in the oral and maxillofacial region. The types of diseases requiring treatment may also differ in the future due to a greater influx of immigrants to the Nordic countries. The wide variety of conditions encountered in a dental practice, as well as variations in the individual patient presentation and response to treatment, defines the need for careful evaluation and synthesis of practice recommendations to provide appropriate and effective management. The field of oral medicine still lacks clear guidelines for various conditions and treatments. Thus, further studies are required to improve patient healthcare. For the discipline of oral medicine, it will be reasonable to take a greater responsibility for the basic medical skills in the dental curriculum, as modern oral medicine is increasingly becoming the intermediate between oral health care and general medicine.

Head and neck cancer (HNC) patients suffer from a range of health-related quality of life (HRQoL) issues, but little is known about their long-term HRQoL. This study explored associations between treatment group and HRQoL at least 5 years' post-diagnosis in HNC survivors. In an international cross-sectional study, HNC survivors completed the European Organization for Research and Treatment of Cancer (EORTC) quality of life core questionnaire (EORTC-QLQ-C30) and its HNC module (EORTC-QLQ-H&N35). Meaningful HRQoL differences were examined between five treatment groups: (a) surgery, (b) radiotherapy, (c) chemo-radiotherapy, (d) radiotherapy ± chemotherapy and neck dissection and (e) any other surgery (meaning any tumour surgery that is not a neck dissection) and radiotherapy ± chemotherapy. Twenty-six sites in 11 countries enrolled 1105 survivors. They had a median time since diagnosis of 8 years, a mean age of 66 years and 71% were male. After adjusting for age, sex, tumour site and UICC stage, there was evidence for meaningful differences (10 points or more) in HRQoL between treatment groups in seven domains (Fatigue, Mouth Pain, Swallowing, Senses, Opening Mouth, Dry Mouth and Sticky Saliva). Survivors who had single-modality treatment had better or equal HRQoL in every domain compared to survivors with multimodal treatment, with the largest differences for Dry Mouth and Sticky Saliva. For Global Quality of Life, Physical and Social Functioning, Constipation, Dyspnoea and Financial Difficulties, at least some treatment groups had better outcomes compared to a general population. Our data suggest that multimodal treatment is associated with worse HRQoL in the long-term compared to single modality.

Background: There is lack of evidence on chronic fatigue (CF) following radiotherapy (RT) in survivors of head and neck cancer (HNC). We aimed to compare CF in HNC survivors > 5 years post-RT with a reference population and investigate factors associated with CF and the possible impact of CF on health-related quality of life (HRQoL). Material and methods: In this cross-sectional study we included HNC survivors treated in 2007-2013. Participants filled in patient-reported outcome measures and attended a one-day examination. CF was measured with the Fatigue Questionnaire and compared with a matched reference population using t-tests and Cohen's effect size. Associations between CF, clinical and RT-related factors were investigated using logistic regression. HRQoL was measured with the EORTC Quality of Life core questionnaire. Results: The median age of the 227 HNC survivors was 65 years and median time to follow-up was 8.5 years postRT. CF was twice more prevalent in HNC survivors compared to a reference population. In multivariable analyses, female sex (OR 3.39, 95 % CI 1.82-6.31), comorbidity (OR 2.17, 95 % CI 1.20-3.94) and treatment with intensity-modulated RT (OR 2.13, 95 % CI 1.16-3.91) were associated with CF, while RT dose parameters were not. Survivors with CF compared to those without, had significantly worse HRQoL. Conclusions: CF in HNC survivors is particularly important for female patients, while specific factors associated with RT appear not to play a role. The high CF prevalence in long-term HNC survivors associated with impaired HRQoL is important information beneficial for clinicians and patients to improve patient follow-up.

Vefir í munni geta orðið fyrir breytingum eða skaða vegna sjúkdóma sem hafa aðallega áhrif á önnur líkamskerfi. Einkenni slíkra altækra sjúkdóma sem birtast í munni geta verið afar breytileg bæði hvað varðar tíðni og birtingarmynd. Einkenni altækra sjúkdóma sem birtast í munni geta verið fyrstu einkenni bráðra eða langvinnra sjúkdóma og geta hafist mörgum árum áður en altæk einkenni koma fram og sjúkdómur greinist.Einnig geta sjúklegar breytingar í munnslímhúð, kjálkum og aðliggjandi svæðum haft áhrif á almennt heilbrigði sjúklings.Vaxandi lífslíkur og framfarir í heilbrigðisþjónustu valda því að líklegt er að fjöldi einstaklinga með einkenni altækra sjúkdóma sem birtast í munni muni aukast jafnt og þétt. Mikilvægt er að bregðast hratt og vel við hugsanlegum einkennum altækra sjúkdóma sem birtast í munni til að auka lífsgæði sjúklinga.Einkenni í munni geta verið fyrstu merki um undirliggjandi altækan sjúkdóm og geta fylgt eða verið undanfari sjúkdómsgreiningar. Tannlæknar gegna því mikilvægu hlutverki við greiningu og tilvísun sjúklinga með hugsanlega altæka sjúkdóma.Ef kviðverkir, niðurgangur og einkenni frá meltingarvegi fylgja einkennum í munni ætti tannlæknir að vísa sjúklingi tafarlaust áfram til nánari læknisrannsóknar. Mikilvægt er að tannlæknir fylgi meðferð sjúklings eftir í samvinnu við lækni þar sem versnun einkenna í munni getur bent til aukinnar sjúkdómsvirkni. Lykilorð: Munnur, altækur, sjúkdómar, einkenn

Background Symptom assessment is key to effective symptom management and palliative care for patients with advanced cancer. Symptom prevalence and severity estimates vary widely, possibly dependent on the assessment tool used. Are symptoms specifically asked about or must the patients add them as additional symptoms? This study compared the prevalence and severity of patient-reported symptoms in two different versions of a multi-symptom assessment tool. In one version, three symptoms dry mouth, constipation, sleep problems were among those systematically assessed, while in the other, these symptoms had to be added as an “Other problem”. Methods This retrospective cross-sectional study included adult patients with advanced cancer at an inpatient palliative care unit. Data were collected from two versions of the Edmonton Symptom Assessment System (ESAS): modified (ESAS-m) listed 11 symptoms and revised (ESAS-r) listed 9 and allowed patients to add one “Other problem”. Seven similar symptoms were listed in both versions. Results In 2013, 184 patients completed ESAS-m, and in 2017, 156 completed ESAS-r. Prevalence and severity of symptoms listed in both versions did not differ. In ESAS-m, 83% reported dry mouth, 73% constipation, and 71% sleep problems, but on ESAS-r, these symptoms were reported by only 3%, 15% and < 1%, respectively. Although ESAS-r severity scores for these three symptoms were higher than on ESAS-m, differences did not reach statistical significance. Conclusion We identified significant differences in patient symptom reporting based on whether symptoms like dry mouth, obstipation and sleep problems were specifically assessed or had to be added by patients as an “Other problem”.

Patients with advanced cancer are prone to develop different opportunistic oral infection due to anti-cancer treatment or the malignancies themselves. Studies of oral fungal samples show an increased prevalence of non-Candida albicans species in mixed oral infections with Candida albicans. Non-C. albicans and C. albicans are associated with varying degrees of resistance to azoles, which may have implications for treatment. This study aimed to assess the diversity and antifungal susceptibility of Candida species detected in the oral cavity. An observational study with microbiological analysis was conducted. Clinical fungal isolates were collected from patients in a hospice unit in 2014–2016. Isolates were re-grown on chromID® Candida plates in 2020. Single colony of each species was re-cultivated and prepared for biochemical identification with a VITEK2® system and verified by gene sequencing. Etest was performed on RPMI agar, and the antifungals fluconazole, amphotericin B, anidulafungin and nystatin were applied. Fifty-six isolates from 45 patients were identified. Seven different Candida species and one Saccharomyces species were detected. The results of biochemical identification were confirmed with sequencing analysis. Thirty-six patients had mono infection, and nine out of 45 patients had 2–3 different species detected. Of C. albicans strains, 39 out of 40 were susceptible to fluconazole. Two non-C. albicans species were resistant to fluconazole, one to amphotericin B and three to anidulafungin. C. albicans was the predominant species, with a high susceptibility to antifungal agents. Different Candida species occur in both mono and mixed infections. Identification and susceptibility testing may therefore lead to more effective treatment and may prevent the development of resistance among patients with advanced cancer. The study Oral Health in Advanced Cancer was registered at ClinicalTrials.gov (#NCT02067572) in 20/02/2014.

The long-term problems of head and neck cancer survivors (HNCS) are not well known. In a cross-sectional international study aimed at exploring the long-term quality of life in this population, 1114 HNCS were asked to state their two most serious long-term effects. A clinician recorded the responses during face-to-face appointments. A list of 15 example problems was provided, but a free text field was also available. A total of 1033 survivors responded to the question. The most frequent problems were ‘dry mouth’ (DM) (n = 476; 46%), ‘difficulty swallowing/eating’ (DSE) (n = 408; 40%), ‘hoarseness/difficulty speaking’ (HDS) (n = 169; 16%), and ‘pain in the head and neck’ (PHN) (n = 142; 14%). A total of 5% reported no problems. Logistic regression adjusted for age, gender, treatment, and tumor stage and site showed increased odds of reporting DM and DSE for chemo-radiotherapy (CRT) alone compared to surgery alone (odds ratio (OR): 4.7, 95% confidence interval (CI): 2.5–9.0; OR: 2.1, CI: 1.1–3.9), but decreased odds for HDS and PHN (OR: 0.3, CI: 0.1–0.6; OR: 0.2, CI: 0.1–0.5). Survivors with UICC stage IV at diagnosis compared to stage I had increased odds of reporting HDS (OR: 1.9, CI: 1.2–3.0). Laryngeal cancer survivors had reduced odds compared to oropharynx cancer survivors of reporting DM (OR: 0.4, CI: 0.3–0.6) but increased odds of HDS (OR: 7.2, CI: 4.3–12.3). This study provides evidence of the serious long-term problems among HNCS.

BACKGROUND:Although dysphagia is a common side effect after radiotherapy (RT) of head and neck cancer (HNC), data on long-term dysphagia is scarce. We aimed to 1) compare radiation dose parameters in HNC survivors with and without dysphagia, 2) investigate factors associated with long-term dysphagia and its possible impact on health-related quality of life (HRQoL), and 3) investigate how our data agree with existing NTCP models. METHODS:This cross-sectional study conducted in 2018-2020, included HNC survivors treated in 2007-2013. Participants attended a one-day examination in hospital and filled in patient questionnaires. Dysphagia was measured with the EORTC QLQ-H&N35 swallowing scale. Toxicity was scored with CTCAE v.4. We contoured swallowing organs at risk (SWOAR) on RT plans, calculated dose-volume histograms (DVHs), performed logistic regression analyses and tested our data in established NTCP models. RESULTS:Of the 239 participants, 75 (31%) reported dysphagia. Compared to survivors without dysphagia, this group had reduced HRQoL and the DVHs for infrahyoid SWOAR were significantly shifted to the right. Long-term dysphagia was associated with age (OR 1.07, 95% CI 1.03-1.10), female sex (OR 2.75, 95% CI 1.45-5.21), and mean dose to middle pharyngeal constrictor muscle (MD-MPCM) (OR 1.06, 95% CI 1.03-1.09). NTCP models overall underestimated the risk of long-term dysphagia. CONCLUSIONS:Long-term dysphagia was associated with higher age, being female, and high MD-MPCM. Doses to distally located SWOAR seemed to be risk factors. Existing NTCP models do not sufficiently predict long-term dysphagia. Further efforts are needed to reduce the prevalence and consequences of this late effect.

Objective Bisphosphonates like alendronate mainly exert their effects on osteoclasts. However, osteoblasts are also affected, but exposed to a much lower concentration in vivo than the osteoclasts. Given that the effects are dose-dependent, the intention of the study was to identify a therapeutically relevant concentration of alendronate for in vitro studies on osteoblasts. Materials and methods Primary human osteoblasts were incubated with alendronate (5, 20 and 100 mu M) for 1, 3, 7 and 14 days. Proliferation and viability were assessed, and the effects on cellular growth and function were evaluated by multianalyte profiling of selected proteins in cell culture media using the Luminex 200(TM). Results The viability was not affected by any of the dosages. Exposure to 5 mu M alendronate had a neutral effect on osteoblast proliferation, and on secretion of osteogenic and inflammatory markers, while enhancing synthesis of a marker of angiogenesis. 20 mu M alendronate induced a decline in proliferation and affected angiogenic and osteogenic biomarkers adversely. 100 mu M alendronate reduced proliferation dramatically, and this dosage was excluded from further experiments. Conclusion A concentration of 5 mu M alendronate exerted effects on human osteoblasts that may translate to those observed in vivo and could therefore be relevant for in vitro studies.

Head and neck cancer (HNC) treatment may lead to late effects and impaired health-related quality of life of survivors. Knowledge on long-term late effects after radiotherapy (RT) and potential underlying biological mechanisms is lacking. We assessed the prevalence of xerostomia, dysphagia, and chronic fatigue (CF) in HNC survivors ≥ 5 years post-RT, and examined associations between pro-inflammatory cytokines and late effects. In a cross-sectional study, 263 HNC survivors treated between 2007 and 2013 were enrolled. They completed validated questionnaires assessing xerostomia and dysphagia (the EORTC QLQ-H N35), and CF (the Fatigue Questionnaire), and underwent blood sampling and clinical examination. Pro-inflammatory cytokines were analyzed in 262 survivors and 100 healthy age- and gender-matched controls. Median time since treatment was 8.5 years. The proportions of survivors reporting xerostomia, dysphagia, and CF were 58

Purpose Our aim was to investigate taste and smell functions in survivors, with a minimum of 2 years follow-up time, after treatment of childhood medulloblastoma/CNS-PNET. Methods This cross-sectional study included 40 survivors treated ≤ 20 years of age. Taste strips with four concentrations of sweet, sour, salt, and bitter were used to assess taste function in all participants. Score from 0-16; ≥ 9 normogeusia, < 9 hypogeusia, and complete ageusia which equals no sensation. No sensation of a specific taste quality equals ageusia of that quality. Thirty-two participants conducted smell testing using three subtests of Sniffin’ sticks; threshold, discrimination, and identification. Together they yield a TDI-score from 1-48; functional anosmia ≤ 16.00, hyposmia >16.00 - < 30.75, normosmia ≥ 30.75 - < 41.50, and ≥ 41.50 super smeller. Results were compared with normative data. Survivors subjectively rated their taste and smell functions using a numerical rating scale (NRS) score 0-10. Results Forty survivors with a mean follow-up of 20.5 years, 13 (32.5 %) were diagnosed with hypogeusia, nine (22.5 %) of these being ageusic of one or more taste qualities. Seventeen (53 %) of 32 participants were diagnosed with hyposmia. Comparing survivors with hyposmia to those with normosmia, a significant difference (p<0.05) was found in TDI-score and in all the subtests. The mean NRS score of subjective ratings of functions were high.Conclusion Our study showed impaired taste and smell functions in long-term survivors of childhood MB/CNS-PNET using objective measurements. However, subjective ratings did not reflect objective findings.