Development of a Patient-Centered Functional Outcomes Questionnaire in Head and Neck Cancer.

Importance: Incorporation of patient perspectives, or patient-reported outcomes, in functional outcome measures has been gaining prominence in the literature on reconstructive surgery. Objective: To create and validate an instrument for measuring the main functional areas of concern for patients with head and neck cancer. Design, Setting, and Participants: This 4-phase mixed-methods qualitative study was conducted from July 1, 2013, to June 30, 2016, in a quaternary head and neck oncology center in Edmonton, Alberta, Canada. Patients were recruited from 3 Head and Neck Research Network sites: University of Alberta (Edmonton, Canada), Mount Sinai Health Network (New York, New York), and University of Turku Hospital (Turku, Finland). The inclusion criteria included 18 years of age or older, diagnosis of squamous cell carcinoma involving the subsites of the head and neck (ie, oral cavity, oropharynx, hypopharynx, and larynx), and at least 1 year since treatment completion. Those patients who were undergoing additional active treatment or with evidence of disease recurrence were excluded. Data were analyzed from July 1, 2013, to June 30, 2016. Main Outcomes and Measures: The primary outcome measures were the clinical correlation of the Edmonton-33 instrument scores with swallowing, speech, dry mouth, and chewing assessment outcomes. Results: In total, 10 patients with head and neck cancer (mean age, 59.6 years; 6 men [60%]) were included in phase 1 of the study, 5 patients (mean age, 55.2 years) were included in phase 2, 10 patients were included in phase 3, and 25 patients with head and neck cancer (mean age, 62.6 years; 14 men [56%]) participated in the phase 4 validation. The Edmonton-33 instrument scores correlated strongly with the swallowing scores of the MD Anderson Dysphagia Inventory (r = 0.77; 95% CI, 0.49-1.0), the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck 35 (EORTC QLQ-H&N35) (r = -0.73; 95% CI, -1.0 to -0.44), and the modified barium swallow test (r = -0.60; 95% CI, -0.94 to -0.25). The instrument scores were also strongly correlated with the Speech Handicap Index scores (r = -0.64; 95% CI, -0.97 to -0.31), word intelligibility scores (r = 0.61; 95% CI, 0.27-0.95), and sentence intelligibility scores (r = 0.55; 95% CI, 0.19-0.91). A moderate to strong correlation was observed between the Edmonton-33 instrument and the EORTC QLQ-H&N35 scores in the dry mouth (r = -0.54; 95% CI, -0.91 to -0.18) and chewing (r = -0.45; 95% CI, -0.84 to -0.06) domains. The factor loading values for the domains of swallowing, speech, dry mouth, and chewing were all greater than 0.3. The mean factor loading values for the items related to swallowing were 0.71 (95% CI, 0.62-0.80) and for the items related to speech were 0.76 (95% CI, 0.72-0.80). The mean factor loading values for the items related to dry mouth were 0.71 (95% CI, 0.59-0.83) and for those related to chewing were 0.77 (95% CI, 0.69-0.85). Conclusions and Relevance: The Edmonton-33 appears to be a validated instrument that will allow patients with head and neck cancer to assess and report their own functional outcomes. It could serve as a single comprehensive measure for functional outcomes.

Craniofacial and oral alterations in patients with Neurofibromatosis 1.

ABTSRACT: Neurofibromatosis type 1 (NF1) is one of the most common inherited syndromes. The literature on craniofacial alterations associated with NF1 has been limited and partially contradictory. This review is based on literature search and the results of the clinical study "Craniofacial and Oral Alterations and Speech in patients with Neurofibromatosis 1", carried out at the University of Turku and Turku University Hospital, Finland in 2006-2012. By the end of 2012, a total of 110 NF1 patients, 54 female and 56 male patients, were examined.A part of our results confirms pre-existing understanding, a part is contradictory to previous considerations based mainly on case reports, and some are entirely novel. Specifically, our results confirmed that enlargement the mandibular canal is the most common abnormality of the mandible in patients with NF1. It should be noted, however, that this finding does not require treatment. Caries was not a major problem. In fact, it was less frequent in NF1 patients compared to reference population. These findings abrogate some previous perceptions. Novel findings of our project include periapical cemental dysplasia in females; short jaws, a finding which usually does not affect bite; and immunohistological analysis of oral mucosal abnormalities. Pioneering study on speech showed that various deviations were very common: As many as 94% of the participants showed some alterations.To conclude, the awareness of craniofacial alterations common in NF1would help avoiding unnecessary and even harmful involvement, e.g. of periapical cemental dysplasia or enlarged mandibular canal which do not require treatment.

Functional and quality of life outcomes after partial glossectomy: a multi-institutional longitudinal study of the head and neck research network.

BACKGROUND: While aggressive treatment for oral cancer may optimize survival, decrements in speech and swallowing function and quality of life often result. This exploratory study investigated how patients recover their communicative function, swallowing ability, and quality of life after primary surgery [with or without adjuvant (chemo)radiation therapy] for tongue cancer over the course of the first year post-operation. METHODS: Patients treated for oral cancer at three institutions (University of Alberta Hospital, Mount Sinai Beth Israel Medical Center, and Turku University Hospital) were administered patient-reported outcomes assessing speech [Speech Handicap Index (SHI)], swallowing [(M.D. Anderson Dysphagia Inventory (MDADI)] and quality of life [European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module (EORTC-H&N35)]. Outcome measures were completed pre-operatively and at 1-, 6-, and 12-months post-operatively. RESULTS: One hundred and seventeen patients undergoing partial glossectomy with reconstruction participated in this study. Results indicated no significant differences in swallowing function (MDADI and EORTC-H&N35 subscales) between baseline and 6 months post-surgery and no significant differences in speech function (SHI subscales) between baseline and 1 year post-surgery. Most quality of life domains (EORTC-H&N35 subscales) returned to baseline levels by 1 year post-operation, while difficulties with dry mouth and sticky saliva persisted. A clear time trend of adjuvant (chemo)radiation therapy negatively affecting dry mouth scores over time was identified in this study, while negative independent effects of chemoradiation on MDADI swallowing, and EORTC-H&N35 swallowing, eating, and opening mouth subscales were found. CONCLUSIONS: Assessment time influenced patient-reported speech, swallowing, and quality of life outcomes, while treatment (by time) effects were found for only swallowing and quality of life outcomes. Results of the present study will help guide clinical care and will be useful for patient counseling on expected short and long-term functional and quality of life outcomes of surgical and adjuvant treatment for oral cavity cancer.

Functional outcomes for clinical evaluation of implant restorations.

The functional outcomes related to treating patients afflicted with tooth loss are an important hallmark in substantiating prosthodontic intervention. The Oral Rehabilitation Outcomes Network (ORONet) conducted two international workshops to develop a core set of outcome measures, including a functional domain. The process followed the general format used in the Outcome Measures in Rheumatology (OMERACT) workshops to develop consensus for clinical outcome measures in arthritis research, which included: developing a comprehensive list of potential outcomes in the literature; submitting them to a filter for validity, clinical discrimination, and feasibility; and ranking those measures meeting all the filter criteria for relative value. The search was conducted to include functional assessments of speech, swallowing, mastication, nutrition, sensation, and motor function as they relate to dental implant therapies. This literature review surveyed 173 papers that produced some result of these descriptors in the functional domain. Of these, 67 papers reported on functional assessments and further defined objective and subjective outcomes. Many of these results were patient-perceived improvements in function, while others were objective assessments based on established methodologies and instruments. Objective evaluations of masticatory function and speech may meet criteria for validity and discriminability for selected interventions, but are generally not feasible for routine use in clinical care settings. The current recommendation is to employ a well-validated survey instrument that covers mastication and speech, such as the Oral Health Impact Profile (OHIP-14, short form), recognizing that patient perceptions of function may differ from objective ability.

Psychologic outcomes in implant prosthodontics.

Consensus regarding outcomes of the treatment of tooth loss, especially the psychologic outcomes, is needed to guide discovery of best practices and enable a better understanding of patient management for this chronic condition. This paper presents the findings of the ORONet Psychological Working Group for prosthodontics and aims to identify psychologic outcomes with properties deemed critical to meet clinical trial and clinical practice needs for the future. References obtained using a PubMed/Medline search were reviewed for clinical outcomes measures of interest. Clinical outcomes measures were judged relative to the criteria of truth, discrimination, and feasibility. Of the psychologic outcome measures identified in this systematic review, only the OHIP-14 was thought to be suitable for use in general practice and multi-institutional outcome registries and clinical trials. Development of clinically useful psychologic outcomes for future use could benefit from developmental methods and tools outlined in the patient-related outcomes field of clinical care.

Economic outcomes in prosthodontics.

PURPOSE: A systematic literature review was conducted to identify the types of economic measures currently used in implant prosthodontics and determine the degree to which cost of care is considered in the context of any positive outcome of the care provided. MATERIALS AND METHODS: A literature search was conducted using the following set of terms plus some additional hand searching: "dental implants" (Mesh) AND ("cost") OR "maintenance" OR "healthcare policy" OR "access to care" OR "third party" OR "economic") AND (("1995/01/01"[PDat]:'2009/12/31"[PDat]) AND (Humans[Mesh]) AND (English[lang])). RESULTS: After a review of the 466 titles and abstracts identified by the search, 18 articles were accepted for further consideration, as some attempt at economic outcome measures was made. An additional four articles were identified by hand searching. The 22 accepted articles were grouped into four basic categories: (1) measure of costs of treatment (direct, indirect, and maintenance costs), (2) cost-effectiveness mathematical modeling applied to simulate the lifetime paths and cost of treatment, (3) cost-effectiveness analysis/cost minimization, and (4) willingness-to-pay, willingness-to-accept. Attempts at determining the costs of treatment varied widely. When the OMERACT filters were applied to the various measures it was felt that discrimination and/or feasibility was a problem for most of the current economic outcome measures. CONCLUSIONS: Measures of cost-benefit, cost-effectiveness, and cost-utility are currently the gold standard; however, feasibility of such analyses is an issue. Collaboration with health economists to guide future research is highly recommended.

Oral Rehabilitation Outcomes Network-ORONet.

The published literature describing clinical evidence used in treatment decisionmaking for the management of tooth loss continues to be characterized by a lack of consistent outcome measures reflecting not only clinical performance but also a range of patient concerns. Recognizing this problem, an international group of clinicians, educators, and scientists with a focus on prosthodontics formed the Oral Rehabilitation Outcomes Network (ORONet) to promote strategies for improving health based on comprehensive, patient-centered evaluations of comparative effectiveness of therapies for oral rehabilitation. An initial goal of ORONet is to identify outcome measures for prosthodontic therapies that represent multiple domains with patient relevance, are amenable to utilization in both institutional and practice-based environments, and have established validity. Following a model used in rheumatology, the group assessed the prosthodontic literature, with an emphasis on implantbased therapies, for outcomes related to longevity and functional, psychologic, and economic domains. These systematic reviews highlight a need for further development of standardized outcomes that can be integrated across clinical and research environments.

Clinical outcomes measures for assessment of longevity in the dental implant literature: ORONet approach.

The Oral Rehabilitation Outcomes Network (ORONet) Longevity Working Group undertook a search of the literature from 1995 to 2009 on randomized controlled trials related to longevity of osseointegrated implants. Outcomes measures used in these studies were identified and subjected to the OMERACT component criteria of truth, validity, and feasibility. Through this process, it was a challenge to identify clinical outcomes measures that fully met the criteria. An attenuated version of the component criteria was applied, and clinical measures were identified for implant outcomes, prosthetic outcomes, and indices. A recommendation on standardized reporting periods was also presented for future consideration. The endpoint of the evaluation process is to develop consensus on clinical outcomes measures that can be applied across broad populations for osseointegrated implant care. The present ORONet initiative represents a beginning toward continual improvement and consensus development for clinical outcomes measures for osseointegrated implants.

Dental age in patients with neurofibromatosis 1.

Neurofibromatosis type 1 (NF1) is a common, hereditary, neurocutaneous skeletal condition with a variety of osseous manifestations. Although NF1 also affects craniofacial structures, the literature has only limited information related to the effect of NF1 on dental development. In this study the dental age of 34 Finnish NF1 patients, 8-17 yr of age, was estimated using the Demirjian & Goldstein method. The dental age of children with NF1 was similar to that of a Finnish control population. The findings suggest that NF1 does not affect the timing of tooth development.

Oral soft tissue alterations in patients with neurofibromatosis.

Our aim was to characterize the type and frequency of oral soft tissue alterations in neurofibromatosis. A total of 103 patients with neurofibromatosis 1 (NF1) and three patients with neurofibromatosis 2 (NF2) were clinically evaluated for their oral soft tissue alterations. Disturbing growths were removed from nine patients with NF1 and from one patient with NF2. The specimens were analyzed using routine histological methods and with immunohistochemistry using antibodies to S100, type IV collagen, CD34, neurofilament, and neuron-specific tubulin (TUBB3). Alterations including oral tumors, overgrowths of gingival soft tissue, and enlarged papillae of the tongue were discovered in 74% of NF1 patients. The results showed that three tumors clinically classified as plexiform neurofibromas and five out of six discrete mucosal tumors displayed histology and immunohistology consistent with that of neurofibroma. The histology of one palatal lesion resembled that of a scar, and the lesion removed from the patient with NF2 was classified as an amyloid tumor. To conclude, oral soft tissue growths are common findings in NF1, but most lesions do not require treatment and the patients may even not be aware of these alterations. Collagen IV, S100, and CD34 are useful biomarkers in the analysis of NF1-related oral soft tissue tumors. The clinicians should recognize that oral soft tissue alterations are relatively common in NF1. Some of the growths are disturbing, and plexiform neurofibromas may bear a risk of malignant transformation.

Radiographic findings in the jaws of patients with neurofibromatosis 1.

PURPOSE: Neurofibromatosis 1 (NF1) is a neurocutaneous-skeletal disorder with variable phenotypic expression and an incidence of 1:3,000 worldwide. The objective was to characterize the NF1-related radiologic alterations found in the jaws of these patients. PATIENTS AND METHODS: In total, 102 patients with NF1 were included in the present study. Six patients had a plexiform neurofibroma in the craniofacial region. RESULTS: Radiologic abnormalities in the jaws were found in 29 of 102 patients with NF1, including 6 patients with plexiform neurofibroma in the head and neck region. The most common radiologic finding was enlargement of the mandibular canal. The most prominent skeletal deformities and alterations of varying severity were detected in the jaws of 6 patients with plexiform neurofibroma. In these patients, the skeletal deformities were seen on the side affected by the tumor and possibly caused by the tumor. In 1 patient, however, the skeletal changes were on the opposite side. CONCLUSIONS: Radiologic abnormalities were found in 29 of 102 patients. The most significant findings were profound deformities of the mandible and maxilla in all 6 patients with plexiform neurofibroma, but not in the other patients. The facial bone deformities found in young patients did not progress markedly at older ages with cessation of the patients' growth.

Short mandible, maxilla and cranial base are common in patients with neurofibromatosis 1.

Neurofibromatosis type 1 (NF1) is an autosomal-dominant neuro-cutaneous-skeletal syndrome. Neurofibromatosis type 1 is one of the Rasopathies, and at the cellular level NF1 results in a hyperactive Ras pathway. In the current investigation, our aim was to study lateral skull X-rays (cephalograms) to assess NF1-related craniofacial morphology. A total of 85 Finnish patients with NF1, including four patients with plexiform neurofibroma of the 5th cranial nerve, and their age- and gender-matched controls, were enrolled in the study. The results showed that patients with NF1 typically had a short mandible, maxilla, and cranial base compared with healthy controls, irrespective of age, but the results were statistically significant only in adults. The length of the mandible, the maxilla and the cranial base correlated with the height of patients under 19 yr of age, but this correlation was absent in adult patients. Thus, a tall adult patient with NF1 may have short jaws and a short cranial base. In conclusion, the NF1 gene apparently influences the growth of craniofacial bones, thus contributing to the craniofacial morphology in NF1.

Neurofibromatosis 1 and dental caries.

A total of 110 patients with neurofibromatosis 1 (NF1) were evaluated for their dental health. Appropriate cohorts from national Finnish databases were used as reference. The results showed that NF1 patients presented lower rate of caries compared to controls in age groups under 35 years. The differences between NF1 patients and the reference population diminished by age. In conclusion, (1) NF1 per se does not predispose to caries; and (2) even if NF1 had an adverse effect on dental health, poor outcome can be counteracted with good personal dental care supported by well organized primary health care. The results of the present study are important to report since a common anecdotal perception is that the rate of caries may be higher in NF1 compared to reference population.

Survey of current functional outcomes assessment practices in patients with head and neck cancer: initial project of the head and neck research network.

BACKGROUND: Functional outcomes assessment has become increasingly important in informing treatment decisions in the area of head and neck cancer. However, consistency of assessment methods across studies has been lacking. For the literature to inform clinical decision making, consensus regarding outcomes measurements is necessary. OBJECTIVE: The Head and Neck Research Network (HNRN) was founded in January 2008 to become a conduit for high-quality research in the area of functional outcomes in patients with head and neck defects. The present study surveyed experts in functional outcomes assessment to determine what are considered the most important tools for assessing speech and swallowing and what background patient characteristics are important to capture. DESIGN, PARTICIPANTS, AND MEASURES: Respondents to the online survey included 54 participants with a background in speech-language pathology, with the majority of respondents from the United States, Canada, and the United Kingdom. RESULTS AND CONCLUSIONS: The results from the survey indicated that clinicians consider both subjective and objective measures as important to use when assessing function. More advanced technical tools were often rated as less important; however, it also was noted that clinicians were most often not able to access these tools or were unfamiliar with them.

Speech after radial forearm free flap reconstruction of the tongue: a longitudinal acoustic study of vowel and diphthong sounds.

The purpose of this study was to use acoustic analyses to describe speech outcomes over the course of 1 year after radial forearm free flap (RFFF) reconstruction of the tongue. Eighteen Canadian English-speaking females and males with reconstruction for oral cancer had speech samples recorded (pre-operative, and 1 month, 6 months, and 1 year post-operative). Acoustic characteristics of formants (F1, F2), fundamental frequency (F0), and duration of 699 vowel and diphthong tokens were analysed. Furthermore, the changes in size of the vowel space area were studied, as well as the effects of radiation therapy (RT) and inclusion of the floor of the mouth (FOM) in the reconstruction. RFFF reconstruction was found to affect several characteristics in males, and a minimal number of variables in females. General signs of reduced ability to articulate were not observed. RT and FOM had no differing effects compared to non-RT or non-FOM. There were individual differences between patients.

Speech characteristics in neurofibromatosis type 1.

Neurofibromatosis 1 (NF1) is a neurocutaneous-skeletal disorder often accompanied with varying degrees of cognitive and motor problems that potentially affect speech and language. While previous studies have shown that NF1 may be associated with a variety of deviations in the patients' speech, they have not investigated the characteristics in phonetic detail. Our clinical observation that many patients share a distinct voice and manner of speaking led to the primary aim of this study, which was to present a comprehensive description of speech in NF1. A total of 62 patients with NF1 (age range 7-66 years), and a control group of 24 speakers (age range 7-62 years) were evaluated for their speech. The test sessions were recorded and the data were analyzed both by ear and by acoustic measurements. The data were analyzed separately by two trained phoneticians, and a summary was produced after comparing the two independent analyses. Various speech problems were observed among patients with NF1. Individual variation was remarkable, but the deviations were more common and severe in children than in adult patients. In addition, men with NF1 had more speech deviations than women with NF1. Findings include deviations in voice quality, problems in regulating pitch, deviant nasality, misarticulation, and disfluency. We suggest that difficulties in speech, particularly in regulating pitch, may have negative social implications. Our results highlight which components of speech require particular attention in speech therapy for patients with NF1.

Periapical cemental dysplasia is common in women with NF1.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a genetic disorder with skeletal involvement. Periapical cemental dysplasia is a rare finding in the normal population. METHOD: A total of 55 patients with NF1, 29 female and 26 male patients, were evaluated with orthopantomograms, supplemented with periapical radiographs if necessary. The vitality of the teeth was measured by two different testing methods. RESULTS: A novel finding was the occurrence of cemental dysplasia affecting the periapical area of vital mandibular teeth in 8 adult women with NF1. Thus, cemental dysplasia was detected in 34.8% of the adult female NF1 patients, while cemental dysplasia was not present in men or children with NF1. CONCLUSION: Periradicular cemental dysplasia is indeed a new NF1 related bone lesion type. Our finding suggests that this is the first reported sexual dimorphism in the manifestations of NF1. Cemental dysplasia of NF1 patients should not be confused with periapical findings caused by endodontic pathoses. The former do not require active therapy whereas in the latter root canal treatment is necessary.

Squamous cell carcinomas arising from different types of oral epithelia differ in their tumor and patient characteristics and survival.

A hypothesis that OSCCs originating from different types of oral epithelia may have different patient and tumor characteristics was evaluated in this retrospective analysis of 188 patients with primary OSCC treated at Turku University Central Hospital, Turku, Finland in 1988-1997. The tumors were categorized according to the type of oral epithelium from which they have originated: (1) specialized epithelium (dorsal tongue) (2) keratinized (masticatory) epithelium, (3) non-keratinized (lining) epithelium, and (4) tongue epithelium (epithelium on the lateral border of the tongue). The relevant clinical data, including age, sex, social status, and risk behavior of the patients and clinical presentation, histopathological grading, and treatment of the tumors, as well as the follow-up information, were collected from the patient charts of the hospital. In general, tumor and patient characteristics of OSCCs and survival rates were found to be in line with those of recent analyses reported from other industrialized countries. However, OSCCs in young patients (4.8%) seemed to be clinically at a lower stage and histologically more highly differentiated than those of the other patients. Eight out of 9 (89%) OSCCs in the young patients were located on the lateral tongue. The 5-year recurrence-free rates of the patients according to the epithelial origin of the tumors were as follows: masticatory epithelium 42%, lining epithelium 57%, and epithelium of the lateral border of the tongue 61%. In conclusion, the tumors originating from different types of oral epithelia may have distinct properties with regard to their clinical behavior and responsiveness to the different treatment modalities. It would seem to be meaningful to investigate the molecular characteristics of the different types of oral epithelium in order to elucidate possible differences in their susceptibility to malignant transformation.

Influence of residual bacteria on periapical tissue healing after chemomechanical treatment and root filling of experimentally infected monkey teeth.

The purpose of this study was twofold: first, to determine the influence on the healing of the periapical tissues when selected bacterial strains and combinations thereof remain after root canal treatment; and, second, the relationship to healing of the quality of the root filling. In eight monkeys, 175 root canals, previously infected with combinations of four or five bacterial strains and with radiographically verified apical periodontitis, were endodontically treated, bacteriologically controlled, and permanently obturated. After 2-2.5 yr, the periapical regions were radiographically and histologically examined. Of these teeth, 48 root canals were also examined for bacteria remaining after removal of the root fillings. When bacteria remained after the endodontic treatment, 79% of the root canals showed non-healed periapical lesions, compared with 28% where no bacteria were found. Combinations of residual bacterial species were more frequently related to non-healed lesions than were single strains. When no bacteria remained, healing occurred independently of the quality of the root filling. In contrast, when bacteria remained, there was a greater correlation with non-healing in poor-quality root fillings than in technically well-performed fillings. In root canals where bacteria were found after removal of the root filling, 97% had not healed, compared with 18% for those root canals with no bacteria detected. The present study demonstrates the importance of obtaining a bacteria-free root canal system before permanent root filling in order to achieve optimal healing conditions for the periapical tissues.