Therapeutic Advances and Challenges for the Management of HPV-Associated Oropharyngeal Cancer.

The use of conventional chemotherapy in conjunction with targeted and immunotherapy drugs has emerged as an option to limit the severity of side effects in patients diagnosed with head and neck cancer (HNC), particularly oropharyngeal cancer (OPC). OPC prevalence has increased exponentially in the past 30 years due to the prevalence of human papillomavirus (HPV) infection. This study reports a comprehensive review of clinical trials registered in public databases and reported in the literature (PubMed/Medline, Scopus, and ISI web of science databases). Of the 55 clinical trials identified, the majority (83.3%) were conducted after 2015, of which 77.7% were performed in the United States alone. Eight drugs have been approved by the FDA for HNC, including both generic and commercial forms: bleomycin sulfate, cetuximab (Erbitux), docetaxel (Taxotere), hydroxyurea (Hydrea), pembrolizumab (Keytruda), loqtorzi (Toripalimab-tpzi), methotrexate sodium (Trexall), and nivolumab (Opdivo). The most common drugs to treat HPV-associated OPC under these clinical trials and implemented as well for HPV-negative HNC include cisplatin, nivolumab, cetuximab, paclitaxel, pembrolizumab, 5-fluorouracil, and docetaxel. Few studies have highlighted the necessity for new drugs specifically tailored to patients with HPV-associated OPC, where molecular mechanisms and clinical prognosis are distinct from HPV-negative tumors. In this context, we identified most mutated genes found in HPV-associated OPC that can represent potential targets for drug development. These include TP53, PIK3CA, PTEN, NOTCH1, RB1, FAT1, FBXW7, HRAS, KRAS, and CDKN2A.

The protective role of postoperative radiation therapy in low and intermediate grade major salivary gland malignancies: A study of the Canadian Head and Neck Collaborative Research Initiative.

BACKGROUND: The objective of this study was to examine the utility of postoperative radiation for low and intermediate grade cancers of the parotid and submandibular glands. METHODS: The authors conducted a retrospective, Canadian-led, international, multi-institutional analysis of a patient cohort with low or intermediate grade salivary gland cancer of the parotid or submandibular gland who were treated from 2010 until 2020 with or without postoperative radiation therapy. A multivariable, marginal Cox proportional hazards regression analysis was performed to quantify the association between locoregional recurrence (LRR) and receipt of postoperative radiation therapy while accounting for patient-level factors and the clustering of patients by institution. RESULTS: In total, 621 patients across 14 tertiary care centers were included in the study; of these, 309 patients (49.8%) received postoperative radiation therapy. Tumor histologies included 182 (29.3%) acinic cell carcinomas, 312 (50.2%) mucoepidermoid carcinomas, and 137 (20.5%) other low or intermediate grade primary salivary gland carcinomas. Kaplan-Meier LRR-free survival at 10 years was 89.0% (95% confidence interval [CI], 84.9%-93.3%). In multivariable Cox regression analysis, postoperative radiation therapy was independently associated with a lower hazard of LRR (adjusted hazard ratio, 0.53; 95% CI, 0.29-0.97). The multivariable model estimated that the marginal probability of LRR within 10 years was 15.4% without radiation and 8.8% with radiation. The number needed to treat was 16 patients (95% CI, 14-18 patients). Radiation therapy had no benefit in patients who had early stage, low-grade salivary gland cancer without evidence of nodal disease and negative margins. CONCLUSIONS: Postoperative radiation therapy may reduce LLR in some low and intermediate grade salivary gland cancers with adverse features, but it had no benefit in patients who had early stage, low-grade salivary gland cancer with negative margins.

Psychosocial outcomes of human papillomavirus (HPV)- and non-HPV-related head and neck cancers: A longitudinal study.

OBJECTIVES: Human papillomavirus (HPV) has prompted a need to further investigate how this new biomarker changes the head and neck cancer (HNC) psychosocial landscape. This study aimed to: (a) characterize the sociodemographic, psychological, and social profiles of patients with HPV-positive versus -negative squamous cell carcinoma of the head and neck; and (b) identify how HPV status contributes to anxiety and depression (primary outcome), quality of life (QoL), and sexuality needs. METHODS: We conducted a prospective longitudinal study of 146 patients newly diagnosed with oral, oropharyngeal, nasopharyngeal, and hypopharyngeal cancer. Seventy-nine patients were HPV-positive and 67 HPV-negative. Patients completed self-administered psychometric measures upon HNC and 3-month follow-up, and Structured Clinical Interviews for DSM Diagnoses. RESULTS: Patients with HPV-negative tumors generally presented with higher anxiety and depression and lower QoL immediately post-HNC diagnosis (<2 weeks) compared to HPV-positive cancers. A Major Depressive Disorder (MDD) immediately post-HNC diagnosis negatively affected patients' anxiety and depression and QoL levels upon diagnosis only when the cancer was HPV-positive. Immediately posttreatment, HPV status was not associated with outcomes. A previous history of suicidal ideation, and upon cancer diagnosis cigarette smoking, anxiety and depression, and feeling close to one's partner were instead explanatory. CONCLUSION: While patients with HPV-positive HNC generally present with initially lower psychological distress, their vulnerability immediately posttreatment indicates an equal need for support. Head and neck clinics may need to better address MDD, anxiety and depression, a prior history of suicidal ideation, health behavior change, and quality of relationships.

Therapeutic Vaccines for HPV-Associated Oropharyngeal and Cervical Cancer: The Next De-Intensification Strategy?

The rise in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has prompted a quest for further understanding of the role of high-risk HPV in tumor initiation and progression. Patients with HPV-positive OPSCC (HPV+ OPSCC) have better prognoses than their HPV-negative counterparts; however, current therapeutic strategies for HPV+ OPSCC are overly aggressive and leave patients with life-long sequalae and poor quality of life. This highlights a need for customized treatment. Several clinical trials of treatment de-intensification to reduce acute and late toxicity without compromising efficacy have been conducted. This article reviews the differences and similarities in the pathogenesis and progression of HPV-related OPSCC compared to cervical cancer, with emphasis on the role of prophylactic and therapeutic vaccines as a potential de-intensification treatment strategy. Overall, the future development of novel and effective therapeutic agents for HPV-associated head and neck tumors promises to meet the challenges posed by this growing epidemic.

Association of Bethesda category and molecular mutation in patients undergoing thyroidectomy.

OBJECTIVES: The aim of this study was to ascertain the relationship between Bethesda category and molecular mutation of thyroid nodules in patients undergoing thyroidectomy. DESIGN: A retrospective cohort of patients who underwent thyroidectomy following needle biopsy and molecular profile testing was performed. SETTING: Two tertiary care academic hospitals. PARTICIPANTS: Consecutive patients with a dominant thyroid nodule who underwent both USFNA and molecular profile testing followed by thyroidectomy were included in the study. MAIN OUTCOME AND MEASURES: The main outcome was postoperative diagnosis of thyroid cancer and aggressivity of disease based on histopathological variants, nodal metastasis or extra-thyroidal extension. Associations between Bethesda category, molecular mutation and postoperative pathology was assessed using descriptive analysis and chi-square testing. RESULTS: Four hundred fifty-one patients were included. 95.9% (93/97) of patients with a BRAFV600E mutation had a Bethesda category V or VI (p < .001), and all had confirmed thyroid cancer on postoperative pathology. Those with H, K or N RAS or EIF1AX mutations, gene expression profiling (GEP) or copy number alterations showed an association with Bethesda categories III and IV (p ≤ .01). Those with no identified molecular mutation had a lower incidence of aggressive thyroid cancer compared to those with an identified mutation (12.6% vs. 44.3%, p < .01). CONCLUSION: BRAFV600E mutations were associated with thyroid cancer subtypes known to be more aggressive whereas RAS and EIF1AX mutations, copy number alterations, and GEP were related to Bethesda categories III and IV. These findings may help thyroid specialists better identify aggressive thyroid nodules associated with indeterminate Bethesda categories.

Longitudinal study indicating antecedent psychosocial vulnerability as predictor of anxiety disorders post-treatment in people with head and neck cancer.

OBJECTIVE: This study aimed to: (1) determine the contribution of pre-cancer psychosocial vulnerability as an independent predictor of anxiety disorder (AD) onset immediately post-treatment in patients diagnosed with a first occurrence of head and neck cancer (HNC), controlling for sociodemographics and medical variables; and (2) estimate prevalence of AD and identify trajectories from the moment of diagnosis to the immediate post-treatment (i.e., over a period of 3 months) in this population. METHODS: Two-hundred twenty-four consecutive patients (participation rate = 72%) newly diagnosed with a primary HNC were assessed with a structured clinical interview for a mental disorder, validated psychometric measures, and medical chart reviews. RESULTS: Twenty-five percent of patients presented a lifetime AD, 19.4% within 2 weeks of HNC diagnosis, and 16.6% immediately post-treatment; representing 26.7% of patients with AD at any timepoint from the moment of diagnosis to immediately post-treatment. Patients were more likely to present an AD immediately post-treatment when they: were diagnosed with advanced-stage cancer (OR = 3.40, p = 0.006), presented a upon cancer diagnosis AD (OR = 2.45, p = 0.008) and/or experienced childhood abuse (OR = 1.96, p = 0.03). CONCLUSIONS: Several AD trajectories may arise when patients are diagnosed with primary HNC. Health professionals should address AD and screen for risk factors (i.e., advanced stage cancer, AD upon cancer diagnosis, history of childhood abuse) as early as possible to assure optimal mental health care in this vulnerable population.

NDRG1 deficiency is associated with regional metastasis in oral cancer by inducing epithelial-mesenchymal transition.

Regional metastasis is the single most important prognostic factor in oral squamous cell carcinoma (OSCC). Abnormal expression of N-myc downstream-regulated genes (NDRGs) has been identified to occur in several tumor types and to predict poor prognosis. In OSCC, the clinical significance of deregulated NDRG expression has not been fully established. In this study, NDRG1 relevance was assessed at gene and protein levels in 100 OSCC patients followed up by at least 10 years. Survival outcome was analyzed using a multivariable analysis. Tumor progression and metastasis was investigated in preclinical model using oral cancer cell lines (HSC3 and SCC25) treated with epidermal growth factor (EGF) and orthotopic mouse model of metastatic murine OSCC (AT84). We identified NDRG1 expression levels to be significantly lower in patients with metastatic tumors compared with patients with local disease only (P = 0.001). NDRG1 expression was associated with MMP-2, -9, -10 (P = 0.022, P = 0.002, P = 0.042, respectively) and BCL2 (P = 0.035). NDRG1 lower expression was able to predict recurrence and metastasis (log-rank test, P = 0.001). In multivariable analysis, the expression of NDRG1 was an independent prognostic factor (Cox regression, P = 0.013). In invasive OSCC cells, NDRG1 expression is diminished in response to EGF and this was associated with a potent induction of epithelial-mesenchymal transition phenotype. This result was further confirmed in an orthotopic OSCC mouse model. Together, this data support that NDRG1 downregulation is a potential predictor of metastasis and approaches aimed at NDRG1 signaling rescue can serve as potential therapeutic strategy to prevent oral cancer progression to metastasis.

Treatment de-escalation for HPV-associated oropharyngeal squamous cell carcinoma with radiotherapy vs. trans-oral surgery (ORATOR2): study protocol for a randomized phase II trial.

BACKGROUND: Patients with human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPC) have substantially better treatment response and overall survival (OS) than patients with HPV-negative disease. Treatment options for HPV+ OPC can involve either a primary radiotherapy (RT) approach (± concomitant chemotherapy) or a primary surgical approach (± adjuvant radiation) with transoral surgery (TOS). These two treatment paradigms have different spectrums of toxicity. The goals of this study are to assess the OS of two de-escalation approaches (primary radiotherapy and primary TOS) compared to historical control, and to compare survival, toxicity and quality of life (QOL) profiles between the two approaches. METHODS: This is a multicenter phase II study randomizing one hundred and forty patients with T1-2 N0-2 HPV+ OPC in a 1:1 ratio between de-escalated primary radiotherapy (60 Gy) ± concomitant chemotherapy and TOS ± de-escalated adjuvant radiotherapy (50-60 Gy based on risk factors). Patients will be stratified based on smoking status (< 10 vs. ≥ 10 pack-years). The primary endpoint is OS of each arm compared to historical control; we hypothesize that a 2-year OS of 85% or greater will be achieved. Secondary endpoints include progression free survival, QOL and toxicity. DISCUSSION: This study will provide an assessment of two de-escalation approaches to the treatment of HPV+ OPC on oncologic outcomes, QOL and toxicity. Results will inform the design of future definitive phase III trials. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03210103. Date of registration: July 6, 2017, Current version: 1.3 on March 15, 2019.

Immediate post-treatment supportive care needs of patients newly diagnosed with head and neck cancer.

OBJECTIVE: This study aimed at identifying supportive care needs of patients with head and neck cancer (HNC-P) immediately post-treatment, finding early predictors of unmet needs, and contrasting how immediate post-treatment needs differed from needs in longer-term survivorship. METHODS: Prospective longitudinal study of 223 consecutive adults (313 approached; 72% participation) newly diagnosed with a first occurrence of primary HNC. Patients completed the Supportive Care Needs Survey-Short Form (SCNS), the Structured Clinical Interview for DSM-IV, and other outcomes. Medical chart reviews were conducted. RESULTS: A total of 68% of patients (n = 145/223) completed the SCNS. The multiple linear regression indicated that when controlled for medical variables, patients presented higher levels of unmet needs when they presented with higher level of anxiety upon HNC diagnosis (p = 0.03), higher neuroticism (p = 0.03), and more stressful life events in the year pre-diagnosis (p = 0.01). Patients immediately post-treatment had a wider variety of unmet needs compared with those in extended survivorship, with psychological unmet needs most prevalent at both time points. Immediately post-treatment, patients needed more support regarding pain (p = 0.04) and worries about treatment results (p = 0.05), whereas patients in longer-term survivorship needed more support regarding anxiety (p = 0.02), changes in sexual relationships (p = 0.04), and fear of death and dying (p = 0.001). CONCLUSION: This study identifies areas needing further development to improve quality of care for HNC-P in the immediate post-treatment period, as well as early determinants of unmet needs. HNC clinics may want to routinely screen for anxiety, neuroticism, and burden from other life events, to pro-actively address needs upon treatment completion and alleviate disease burden.

Radiotherapy versus transoral robotic surgery and neck dissection for oropharyngeal squamous cell carcinoma (ORATOR): an open-label, phase 2, randomised trial.

BACKGROUND: Transoral robotic surgery (TORS) with concurrent neck dissection has supplanted radiotherapy in the USA as the most common treatment for oropharyngeal squamous cell carcinoma (OPSCC), yet no randomised trials have compared these modalities. We aimed to evaluate differences in quality of life (QOL) 1 year after treatment. METHODS: The ORATOR trial was an investigator-initiated, multicentre, international, open-label, parallel-group, phase 2, randomised study. Patients were enrolled at six hospitals in Canada and Australia. We randomly assigned (1:1) patients aged 18 years or older, with Eastern Cooperative Oncology Group scores of 0-2, and with T1-T2, N0-2 (≤4 cm) OPSCC tumour types to radiotherapy (70 Gy, with chemotherapy if N1-2) or TORS plus neck dissection (with or without adjuvant chemoradiotherapy, based on pathology). Following stratification by p16 status, patients were randomly assigned using a computer-generated randomisation list with permuted blocks of four. The primary endpoint was swallowing-related QOL at 1 year as established using the MD Anderson Dysphagia Inventory (MDADI) score, powered to detect a 10-point improvement (a clinically meaningful change) in the TORS plus neck dissection group. All analyses were done by intention to treat. This study is registered with ClinicalTrials.gov (NCT01590355) and is active, but not currently recruiting. FINDINGS: 68 patients were randomly assigned (34 per group) between Aug 10, 2012, and June 9, 2017. Median follow-up was 25 months (IQR 20-33) for the radiotherapy group and 29 months (23-43) for the TORS plus neck dissection group. MDADI total scores at 1 year were mean 86·9 (SD 11·4) in the radiotherapy group versus 80·1 (13·0) in the TORS plus neck dissection group (p=0·042). There were more cases of neutropenia (six [18%] of 34 patients vs none of 34), hearing loss (13 [38%] vs five [15%]), and tinnitus (12 [35%] vs two [6%]) reported in the radiotherapy group than in the TORS plus neck dissection group, and more cases of trismus in the TORS plus neck dissection group (nine [26%] vs one [3%]). The most common adverse events in the radiotherapy group were dysphagia (n=6), hearing loss (n=6), and mucositis (n=4), all grade 3, and in the TORS plus neck dissection group, dysphagia (n=9, all grade 3) and there was one death caused by bleeding after TORS. INTERPRETATION: Patients treated with radiotherapy showed superior swallowing-related QOL scores 1 year after treatment, although the difference did not represent a clinically meaningful change. Toxicity patterns differed between the groups. Patients with OPSCC should be informed about both treatment options. FUNDING: Canadian Cancer Society Research Institute Grant (#701842), Ontario Institute for Cancer Research Clinician-Scientist research grant, and the Wolfe Surgical Research Professorship in the Biology of Head and Neck Cancers grant.

Contribution of psychiatric diagnoses to extent of opioid prescription in the first year post-head and neck cancer diagnosis: A longitudinal study.

PURPOSE: The purpose of this study was to determine, within the first-year post-head and neck cancer (HNC) diagnosis, the contribution of past and upon HNC psychiatric diagnoses (ie, substance use disorder, major depressive disorder, and anxiety disorder) to the extent (ie, cumulated dose) of opioid prescription. METHODS: Prospective longitudinal study of 223 consecutive adults (on 313 approached; 72% participation) newly diagnosed (<2 weeks) with a first occurrence of primary HNC, including Structured Clinical Interviews for DSM-IV disorders, validated psychometric measures, and medical chart reviews. Opioid doses were translated into standardized morphine milligram equivalents (MME) using CDC guidelines. A model of variables was tested using multiple linear regression. RESULTS: Fifty-five percent (123/223) of patients received opioids at some point during the first 12 months post-HNC diagnosis, 37.7% (84/223) upon HNC diagnosis (pre-treatment), 40.8% (91/223) during treatments, and 31.4% (70/223) post-treatment. The multiple linear regression indicated that an AD (P = 0.04) upon HNC diagnosis in early stage contributes to cumulated MME dose in the first year post-HNC diagnosis. CONCLUSION: This study underlines how anxiety has important repercussions on the management of pain and illustrates the importance of screening for AD upon HNC diagnosis to allow for early prophylactic treatment and support.

Development and validation of the McGill body image concerns scale for use in head and neck oncology (MBIS-HNC): A mixed-methods approach.

OBJECTIVE: The aim of this study was to develop and validate a patient-reported outcome measure to evaluate body image concerns in head and neck cancer (HNC) patients. METHODS: Items were created using a combination of deductive (eg, US Food and Drug Administration Qualification of Clinical Outcome Assessments, literature review) and inductive approaches (eg, subject matter experts, HNC patients). Items were translated for use in both Canadian English and Canadian French using back-translation. A two-step empirical validation process using the Classical Test Theory (CTT) and Rasch Measurement Theory (RMT) was conducted with 224 and 258 HNC patients, respectively, having undergone disfiguring surgery within the past 3 years. RESULTS: Analyses suggest two subscales for MBIS-HNC: social discomfort (10 items) and negative self-image (11 items). The McGill Body Image Concerns Scale-Head and Neck Cancer (MBIS-HNC) is reliable with high internal consistency (0.98), high test-retest reliability over a two-week period (ICC = 0.88), moderate to high convergent validity (range r = 0.43-0.81), and divergent validity (range r = 0.12-0.15). RMT was used in addition to CTT. Disordered thresholds led to the modification of the number of response options, and items were deleted based on differential item functioning and high local dependency. Unidimensionality of both subscales and supporting a total score was confirmed. The measure was however characterized by the presence of an important floor effect, confirmed with poor targeting as demonstrated by the person-item threshold distribution. CONCLUSION: Evidence gathered from our theory-driven validation study using CTT and RMT provides practitioners and researchers with a useful and easy to use self-report measure.

Barriers to psychosocial oncology service utilization in patients newly diagnosed with head and neck cancer.

OBJECTIVES: While patients with head and neck cancer (HNC) are known to experience higher levels of anxiety and depression, they do not always use psychosocial oncology (PSO) services when available. This study aimed to investigate barriers to PSO service utilization in this patient population, with the goal of appropriately targeting outreach interventions. METHODS: A conceptual model based on the Behavioral Model of Health Services Use was tested in 84 patients newly diagnosed with a first occurrence of HNC followed longitudinally over 1 year, including variables collected through self-administered questionnaires, Structured Clinical Interviews for DSM (SCID-I), and medical chart reviews. RESULTS: Within the first-year post-diagnosis, 42.9% of HNC patients experienced clinical levels of psychological distress, with only 50% of these consulting PSO services (29% total). A logistic regression indicated that PSO utilization was increased when patients presented with advanced cancer (P = 0.04) and a SCID-I diagnosis of major depressive disorder, anxiety disorder, or substance use disorder (P = 0.02), while there was an inverse relationship with self-stigma of seeking help (P = 0.03); these variables together successfully predicted 76.3% of overall PSO utilization, including 90.6% of non-users. CONCLUSIONS: Future outreach interventions in patients with HNC could address stigma in an attempt to enhance PSO integration into routine clinical care.

A screening algorithm for early detection of major depressive disorder in head and neck cancer patients post-treatment: Longitudinal study.

OBJECTIVE: The primary purpose of this study was to identify predictors of Major Depressive Disorder in head and neck cancer (HNC) patients in the immediate post-treatment period (ie, at 3 months post-diagnosis), with a focus on previously unexamined historical and contextual factors. METHODS: Prospective longitudinal study of 223 consecutive adults (72% participation) newly diagnosed with a first occurrence of primary HNC, including validated psychometric measures, Structured Clinical Interviews for DSM Disorders, and medical chart reviews. RESULTS: The 3-month period prevalence of Major Depressive Disorder was 20.4%; with point prevalences of 6.8% upon HNC diagnosis, 14.2% at 3 months, and 22.6% lifetime. Patients most susceptible to developing Major Depressive Disorder in the immediate post-treatment period: were diagnosed with advanced-stage cancer rather than early-stage cancer (O.R. = 4.94, P = 0.04), received surgery only (O.R. = 8.73, P = 0.04), presented a lifetime history of Anxiety Disorder on SCID-I (O.R. = 6.62; P = 0.01), and indicated higher pre-treatment levels of anxiety on the HADS (O.R. = 0.45, P = 0.05). CONCLUSIONS: Our results outline the predominant role of anxiety upon diagnosis as a precursor to post-treatment Major Depressive Disorder, suggesting the need for identification and prophylactic treatment of anxiety upon diagnosis in head and neck cancer patients. Further investigation into pathways by which pre-treatment anxiety predisposes to post-treatment Major Depressive Disorder in this population is warranted.

Thyroid cancer patients receiving an interdisciplinary team-based care approach (ITCA-ThyCa) appear to display better outcomes: Program evaluation results indicating a need for further integrated care and support.

BACKGROUND: Thyroid cancer (ThyCa) is generally associated with a favorable prognosis and excellent surgical outcomes. Consequently, its treatment is medically focused and current guidelines recommend interdisciplinary care including access to a nurse for complex cases alone. To date, no studies have evaluated the need for and impact of an Interdisciplinary Team-based Care Approach (ITCA-ThyCa) for general thyroid cancer patients, including a dedicated nurse as part of a larger interdisciplinary team, as well as patient-reported outcomes, as is recommended worldwide in cancer care. Our aim was to evaluate such a program. METHODS: The ITCA-ThyCa was evaluated within a quasi-experimental design using the Centers for Disease Control Framework for Program Evaluation, including process and outcome measures. Patients eligible were adults with a biopsy indicating confirmed or highly suspicious ThyCa (TNM-Classification + Bethesda score of V/VI). The intervention group (IG) received ITCA-ThyCa and the comparison group (CG), usual care alone. RESULTS: In our sample comprised of 200 participants (122 IG; 78 CG), ITCA-ThyCa patients appeared to show significantly better outcomes than CG patients, namely, higher levels of overall well-being (P = .001) and fewer physical (P = .003) and practical (P = .003) issues and concerns. More satisfied with their overall care (P = .028), including care coordination (P = .049), they reported their health care provider as more approachable (P = .007), respectful (P = .005), and trustworthy (P = .077; trend) and were more likely to recommend their hospital (P = .02). Ninety-eight percent of IG patients recommended ITCA-ThyCa. CONCLUSION: Data from our program illustrates that hospital resources should not be allocated based on medical trajectory alone and challenges the idea that ThyCa is "straightforward." ThyCa patients seem to experience symptom distress at a level comparable to-or exceeding-that of general oncological patients despite their promising medical outcomes, indicating that better integrated care and support are in order.

CALCITONIN SECRETORY INDEX AND UNSUSPECTED NODAL DISEASE IN MEDULLARY THYROID CARCINOMA.

OBJECTIVE: Medullary thyroid carcinoma (MTC) is a rare thyroid malignancy originating from parafollicular C-cells with the potential for aggressive behavior. The extent of lymph node (LN) dissection at the time of surgery is controversial, with different schools of thought prevailing. Some systematically perform LN dissections, whereas others base their decision on radiologic evidence of disease and some with the assistance of pre-operative calcitonin (CT) levels. METHODS: We retrospectively assessed the correlation between pre-operative CT levels and clinico-pathologic factors among 42 patients with MTC between 1994 and 2015. Furthermore, we refined the use of pre-operative serum CT levels and explored for the first time a test called the Calcitonin Secretory Index (CSI, ng/mL/mm). RESULTS: Pre-operative CT levels correlated independently with tumor size ( P<.0001), number of metastatic LNs ( P<.01), and increased rates of distant metastasis. The CSI better predicted early LN disease ( P<.045). Patients with early LN metastasis had a CSI >30 ng/mL/mm, a representative threshold above which the surgical cure declines considerably. CONCLUSION: In our experience, pre-operative CT levels and now the CSI appear as sensitive and specific risk stratification markers for MTC. Despite negative findings on dedicated pre-operative neck imaging in addition to total thyroidectomy, a CSI >30 ng/mL/mm would prompt bilateral central node dissection. Due to the small sample size, our study provides preliminary evidence of the value of CSI in clinical practice. ABBREVIATIONS: ANOVA = analysis of variance; ATA = American Thyroid Association; CSI = Calcitonin Secretory Index; CT = calcitonin; LN = lymph node; MTC = medullary thyroid carcinoma; ROC = receiver operating characteristic.

Dual-Energy CT Characteristics of Parathyroid Adenomas on 25-and 55-Second 4D-CT Acquisitions: Preliminary Experience.

OBJECTIVE: The objective of this study was to compare the dual-energy computed tomography (CT) characteristics of parathyroid adenomas (PAs), thyroid tissue, and lymph nodes (LNs) and assess whether the spectral information can improve distinction of these tissues. METHODS: Dual-energy CT scans from 20 patients with pathologically proven PAs were retrospectively evaluated, identifying 19 eligible PAs and region of interest analysis used for spectral characterization. RESULTS: There was a significant difference in multiple spectral parameters between PAs, LNs, and the thyroid gland (P < 0.05-0.0001). The greatest difference in spectral characteristics of PAs compared with that of LNs was on the 25-second acquisition, whereas the 55-second acquisition was better for distinguishing PAs from the thyroid gland. CONCLUSIONS: Four-dimensional CT acquired in dual-energy CT mode has the potential to further enhance diagnostic accuracy for PA identification on individual phases of the perfusion study.

Recovering function and surviving treatments are primary motivators for health behavior change in patients with head and neck cancer: Qualitative focus group study.

OBJECTIVE: Against medical advice, head and neck cancer (HNC) patients have been shown to continue to smoke and misuse alcohol post-diagnosis and treatment. This study aimed to better understand the barriers to and facilitators of health behavior change (HBC) in HNC patients. METHOD: We conducted nine focus groups following a standard protocol. Eligible patients were diagnosed less than three years previously with a primary HNC and selected using maximum variability sampling (gender, age, cancer stage, smoking, and alcohol misuse). Thematic analysis was conducted using NVivo 10 software. RESULTS: Participants were mostly men (79%), 65 years of age (SD = 10.1), and married/common-law (52%, n = 15). Mean time from diagnosis was 19 months (SD = 12.3, range = 5.0-44.5), and most had advanced cancer (65.5%, n = 19). Participants provided a larger than anticipated definition of health behaviors, encompassing both traditional (smoking, drinking, diet, exercise, UV protection) and HNC-related (e.g., dental hygiene, skin care, speech exercises, using a PEG, gaining weight). The main emerging theme was patient engagement, that is, being proactive in rehabilitation, informed by the medical team, optimistic, flexible, and seeking support when needed. Patients were primarily motivated to stay proactive and engage in positive health behaviors in order to return to normal life and reclaim function, rather than to prevent a cancer recurrence. Barriers to patient engagement included emotional aspects (e.g., anxiety, depression, trauma, demoralization), symptoms (e.g., fatigue, pain), lack of information about HBC, and healthcare providers' authoritarian approach in counseling on HBC. We found some commonalities in barriers and facilitators according to behavior type (i.e., smoking/drinking/UV protection vs. diet/exercise). SIGNIFICANCE OF RESULTS: This study underlines the key challenges in addressing health behaviors in head and neck oncology, including treatment-related functional impairments, symptom burden, and the disease's emotional toll. This delicate context requires health promotion strategies involving close rehabilitative support from a multidisciplinary team attentive to the many struggles of patients both during treatments and in the longer-term recovery period. Health promotion in HNC should be integrated into routine clinical care and target both traditional and HNC-related behaviors, emphasizing emotional and functional rehabilitation as key components.

Treatment of base of tongue cancer, stage III and stage IV with primary surgery: survival and functional outcomes.

This study examines functional outcome (speech and swallowing), survival, and disease control in patients receiving an intensified treatment regimen with primary aggressive surgery, and postoperative radiotherapy or postoperative concomitant chemoradiotherapy, for previously untreated, resectable, stage III and IV squamous cell carcinoma (SCC) of the tongue base. Sixty-six consecutive patients treated from June 1997 to June 2006 were followed prospectively through the Multidisciplinary Head and Neck Surgery Reconstruction Clinic. Speech and swallowing data were gathered at four evaluation times during the first year. Speech assessment was conducted by PERCI, Nasometer, and C-AIDS and swallowing assessment by Modified barium swallow, Diet survey and G-tube. Also, the overall survival, disease-specific survival and loco regional control were measured. The average age of the patients was 56.8, 85 % male and 15 % female. All patients had primary surgical resection and 83 % received postoperative radiotherapy and 17 % chemoradiation therapy. Overall survival at 3 years was 80.3 % and 5 years 52.2 %. Disease-specific survival at 3 years was 86.7 % and 5 years was 77.5 %. Local control was 94 %. Distal metastasis and second primary were found to be 7.5 % each. Primary surgical treatment of advanced BOT cancer offers excellent functional outcome, local control and disease-specific survival.

Looking beyond disfigurement: the experience of patients with head and neck cancer.

Despite the frequent occurrence of head and neck cancer (HNC) disfigurement, little is known about its psychosocial impact on patients. This study aimed to understand the lived experience of disfigurement in HNC and explore what patients considered to be its influences. Fourteen disfigured HNC patients participated in a 45-to-120-minute in-depth, semistructured interview, which was analyzed qualitatively using interpretive phenomenology. A majority of participants (64 percent) were considered to be at an advanced cancer stage (stage III or stage IV). Patients' experiences revolved around the concept of a ruptured self-image (a discontinuity in sense of self). Forces triggering this ruptured self-image created a sense of "embodied angst", in which disfigurement served as a constant reminder of the patient's cancer and associated foundational malaise. Other influences fostered a sense of normalcy, balance, and acceptance. Participants oscillated between these two states as they grew to accept their disfigurement. This study's findings could guide supportive interventions aimed at helping patients face head and neck surgery.