Osteoradionecrosis versus Cancer Recurrence: An Unresolved Clinical Dilemma.

INTRODUCTION: Osteoradionecrosis is a rare and debilitating risk of definitive chemoradiotherapy for head and neck squamous cell carcinoma. It is difficult to distinguish between osteoradionecrosis and recurrent or progressive disease, as clinical and radiologic features may be similar. Our aim was to compare the clinical presentation and radiologic features of osteonecrosis with those of recurrent or progressive cancer. METHODS: We conducted a single-center case series of 19 patients with head and neck squamous cell carcinoma diagnosed between 2011 and 2019 who subsequently developed clinical and/or radiological suspicion of osteoradionecrosis. The population was a referred sample from head and neck cancer physicians at Northwell Health Cancer Institute. Clinician notes and imaging reports were reviewed to assign a final diagnosis of either cancer, osteonecrosis, or indeterminate. RESULTS: No differences were found in the clinical presentation or radiologic features between groups. Median time between treatment and development of symptoms was longer in patients with a final diagnosis of osteoradionecrosis than recurrent or progressive disease (5 vs. 3 months), but this difference was not statistically significant. Radiation dose and type were not associated with diagnosis. Mean standard uptake value maximums on positron emission tomography/computed tomography were significantly higher in the cancer group (median 14.8 vs. 9.1, p < 0.0152). At 1 year after first suspicion of osteoradionecrosis, 100% of osteoradionecrosis patients were alive, versus 28.6% of cancer patients. DISCUSSION/CONCLUSION: There is significant overlap in clinical and radiologic features of osteoradionecrosis and cancer. Standard uptake maximums may be helpful in predicting diagnosis. Occurrence of symptoms within 6 months of completing chemoradiotherapy should raise the concern for malignancy.

Oropharyngeal tumor cells induce COX-2 expression in peripheral blood monocytes by secretion of IL-1α.

Oropharyngeal squamous cell cancer (OPC) accounts for 3% of all cancers and greater than 1.5% of all cancer deaths in the United States, with marked treatment-associated morbidity in survivors. More than 80% of OPC is caused by HPV16. Tumors induced by HPV have been linked to impaired immune functions, with most studies focused on the local tumor microenvironment. Fewer studies have characterized the effects of these tumors on systemic responses in OPC, especially innate responses that drive subsequent adaptive responses, potentially creating feed-back loops favorable to the tumor. Here we report that elevated plasma levels of PGE2 are expressed in half of patients with OPC secondary to overexpression of COX-2 by peripheral blood monocytes, and this expression is driven by IL-1α secreted by the tumors. Monocytes from patients are much more sensitive to the stimulation than monocytes from controls, suggesting the possibility of enhanced immune-modulating feed-back loops. Furthermore, control monocytes pre-exposed to PGE2 overexpress COX-2 in response to IL-1α, simulating responses made by monocytes from some OPC patients. Disrupting the PGE2/IL-1α feed-back loop can have potential impact on targeted medical therapies.

A Mobile Patient-Facing App for Tracking Patient-Reported Outcomes in Head and Neck Cancer Survivors: Single-Arm Feasibility Study.

BACKGROUND: Patients with head and neck cancer (HNC) frequently experience disease-related symptoms and treatment adverse effects that impact their overall quality of life. Cancer-specific mobile health apps for patient-related outcomes allow patients to communicate with their clinicians and proactively track their symptoms, which have been shown to improve clinical management and disease outcomes. OBJECTIVE: The purpose of this study was to evaluate the feasibility of LogPAL, a novel iPhone-based mobile health app designed to help HNC survivors track and manage their posttreatment symptoms. METHODS: Patients who completed curative treatment for HNC in the preceding 24 months were recruited from 2 clinical sites within a single institution. Upon enrollment, participants completed a brief sociodemographic survey, downloaded the app onto their iPhone devices, and were asked to complete a series of biweekly questionnaires (based on the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events) via the app for an 8-week study period. The primary feasibility endpoints included retention (retaining >80% of the enrolled participants for the duration of the study period), adherence (>50% of the participants completing 100% of the questionnaires over the study period), and usability (a mean system usability scale [SUS] score >68). Additional postintervention questions were collected to assess perceived usefulness, acceptance, and overall satisfaction. RESULTS: Between January and October 2019, 38 participants were enrolled in the study. Three participants dropped out, and 3 were classified as nonusers. The remaining 32 (87%) were eligible for analysis. Their mean age was 57.8 (SD 12.3) years (range 24-77 years, 81% [26/32] male). Overall, 375 of 512 (73.2%) questionnaires were completed, with 17 (53%) of the 32 participants adherent. Participant-reported usability was acceptable; the mean SUS score was 71.9 (95% CI 64.3-79.5) with high satisfaction of LogPAL usefulness and likelihood to recommend to other cancer survivors. CONCLUSIONS: This single-arm prospective pilot study showed that LogPAL is a feasible, regularly used, accepted app for HNC survivors, justifying a full-scale pilot. Based on the findings from this study, future iterations will aim to improve usability and test intervention efficacy.

Impact of stereotactic body radiation therapy on geriatric assessment and management for older patients with head and neck cancer using G8.

PURPOSE: Management of head and neck cancers (HNC) in older adults is a common but challenging clinical scenario. We assess the impact of Stereotactic Body Radiation Therapy (SBRT) on survival utilizing the Geriatric-8 (G8) questionnaire. MATERIALS AND METHODS: 171 HNC patients, deemed medically unfit for definitive treatment, were treated with SBRT ± systemic therapy. G8 questionnaires were collected at baseline, at 4-6 weeks, and at 2-3 months post-treatment. Patients were stratified according to their baseline G8 score: <11 as 'vulnerable', 11-14 as 'intermediate', and >14 as 'fit'. Overall survival (OS) was assessed through univariate Kaplan Meier analysis. Repeated measures ANOVA was used to determine if baseline characteristics affected G8 score changes. RESULTS: Median follow-up was seventeen months. 60% of patients presented with recurrent HNC, 30% with untreated HNC primaries, and 10% with metastatic non-HNC primaries. Median age was 75 years. Median Charlson Comorbidity Index score was 2. 51% of patients were 'vulnerable', 37% were 'intermediate', and 12% were 'fit' at baseline, with median survival of 13.2, 24.3, and 41.0 months, respectively (p = .004). Patients who saw a decrease in their follow-up G8 score (n = 69) had significantly lower survival than patients who had stable or increased follow-up G8 scores (n = 102), with median survival of 8.6 vs 36.0 months (p < .001). CONCLUSION: The G8 questionnaire may be a useful tool in upfront treatment decision-making to predict prognosis and prevent older patients from receiving inappropriate anti-cancer treatment. Decline in follow-up G8 scores may also predict worse survival and aid in goals of care following treatment.

Evaluating of HPV-DNA ISH as an adjunct to p16 testing in oropharyngeal cancer.

AIM: Current guidelines recommend p16 immunohistochemistry (IHC) for testing human papillomavirus (HPV) in oropharyngeal carcinoma (OPSCC). We evaluated the value of adding DNA in situ hybridization (ISH) to p16 IHC. METHODS: Fifty patients with OPSCC were analyzed. Concordance between HPV-DNA ISH and p16 IHC was measured by Gwet's agreement coefficient. RESULTS: p16 IHC was positive in 35/48 (72.9%), negative in 8/48 (16.7%) patients. Wide spectrum DNA-ISH was positive in 9/23 (39%) and negative in 14/23 (60.9%) patients. High-risk 16/18 (HR) HPV DNA-ISH was positive in 11/23 (47.8%) and negative in 12 (52.2%) patients. The agreement between HPV DNA-ISH and p16 IHC is fair (Gwet's AC1 = 0.318). CONCLUSION: The agreement between p16 IHC and HPV-DNA ISH was fair. However, ISH sensitivity was low. Our findings add to the current data that p16 IHC testing is reliable and may be enough as a stand-alone test for HPV detection in OPSCC.

Improving post-CRT neck assessment in patients with HPV-associated OPSCC (Review).

The positive predictive value (PPV) of 12-week post-therapy FDG-PET/CT is low in patients with Human Papillomavirus (HPV)-associated Oropharyngeal Squamous Cell Carcinoma (OPSCC) after treatment with definitive chemoradiation (CRT). Moreover, the diagnostic performance of post-CRT fine needle aspiration (FNA) in detecting persistent disease is unknown in this population. Given these important shortcomings in post-CRT treatment assessment, head and neck oncologists are limited in appropriately selecting patients for consolidative neck dissection, which results in over-treatment of a favorable risk population. Using the PubMed database, we performed a literature review of published series in HPV-associated OPSCC to investigate potential strategies for improvement of post-CRT neck assessment. Several different approaches were found, including continued surveillance with PET/CT, delayed timing of restaging PET/CT, initial response evaluation with multimodality or alternative imaging, and detection of circulating HPV DNA. At present, the optimal approach to post-CRT treatment assessment is unclear; further investigation and incorporation of new technologies and surveillance protocols will be highly beneficial for patients with HPV-associated OPSCC.

Identifying patterns of failure and secondary primary malignancies in HPV-related oropharyngeal squamous cell carcinomas.

Aim: To compare patterns and rates of recurrence in patients with oropharyngeal squamous cell carcinoma by human papilloma virus (HPV) status. Patients & methods: Retrospective chart review of 155 patients diagnosed with oropharyngeal squamous cell carcinoma between 2012 and 2014 at a single center. Results: Two-year recurrence-free survival was higher in patients with HPV-positive tumors compared with negative (85.2% [standard error = 0.03] versus 59.3% [standard error = 0.09]; p < .001) with the former proportionally less likely to have locoregional recurrence. HPV-positive patients had proportionally higher incidence of second primary malignancies outside of head, neck and lung compared with HPV-negative (74.2 vs 37.5%; p = 0.09). Conclusion: The differences in failure by HPV status indicates a need for modified surveillance guidelines. The differences in second primary malignancies patterns are interesting, warranting further evaluation in larger studies.

The use of 3D printing in shared decision making for a juvenile aggressive ossifying fibroma in a pediatric patient.

Juvenile aggressive ossifying fibromas (JAOF) are rare, typically benign pediatric tumors that are locally aggressive and have high recurrence rates. A 7-year old male presented with a palatal mass and a 3D printed model was created and used as a visual aide to highlight the importance of management in terms of functional, cosmetic, and disease-free outcomes with the family. The patient ultimately underwent successful enucleation with final pathology consistent with JAOF. To our knowledge, this is the first description of the use of 3D printing to help in the shared decision-making process for the treatment of this aggressive tumor.

Management of the neck after definitive chemoradiation in patients with HPV-associated oropharyngeal cancer: An institutional experience.

PURPOSE: To investigate the multidisciplinary management of patients with Human Papilloma Virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) and an incomplete nodal response on restaging PET/CT after definitive chemoradiation (CRT). MATERIALS AND METHODS: A retrospective chart review was performed of patients diagnosed with node-positive HPV-associated OPSCC from 2012 to 2017, who underwent definitive upfront CRT, and had an incomplete response on post-therapy PET/CT according to NCCN criteria. Post-CRT PET/CT results, management decisions, and clinical outcomes were recorded. RESULTS: Seventy-four patients with node-positive HPV-associated OPSCC were identified; 20 patients with incomplete neck response on PET/CT according to NCCN criteria were included in the final case series. Median follow-up time was 33 months. Patients were managed as follows: 8 underwent observation and surveillance imaging, 6 underwent ultrasound-guided fine needle aspiration (FNA), and 6 had immediate neck dissection. All the observed patients were disease-free at most recent follow-up. None of the patients who underwent immediate neck dissection had residual neck disease on pathological examination; two patients in this group ultimately developed metastatic disease. Among the 6 who underwent FNA, 1 individual had positive pathology, along with residual primary disease, for which the patient underwent salvage surgery. The 5 remaining individuals had negative FNA results, were subsequently observed, and remained free of disease. CONCLUSIONS: This institutional experience supports the notion of a high threshold for neck dissection in this low-risk population; only 1 of 20 patients with suspicious PET/CT findings had residual disease in the neck. Moreover, these patients should be managed by a multidisciplinary tumor board (MTB) since current algorithms do not universally include HPV status. Finally, the use of restaging PET/CT to guide management of the neck can be improved with changes in terminology and consideration of FDG-avidity at the primary site and on pre-therapy scans.

Outcomes of nonsurgical management of locally advanced carcinomas of the sinonasal cavity.

OBJECTIVE: To determine the outcome of definitive concurrent chemoradiation with platinum for locally advanced sinonasal carcinomas. STUDY DESIGN: Retrospective cohort. METHODS: Twenty-three nonsurgically and definitively treated patients diagnosed between July 1998 and February 2009 were analyzed. Patients with adenoid cystic carcinoma or adenocarcinoma were treated with photons and neutrons; the other histologies received photons alone. The vast majority received chemotherapy. Descriptive statistics were utilized, and Kaplan-Meier estimates were computed. RESULTS: Female (57%) and Caucasian (74%) preponderance were observed. Eighty-seven percent were unresectable; the maxillary and nasoethmoid sites were equally prevalent. Intensity-modulated radiation therapy (IMRT) and photons alone were utilized in 74% and 70%, respectively. Platinum agents were given in 95% of chemotherapy patients. Complete response was observed in 64% of patients. Median progression-free survival (PFS) and overall survival (OS) were 28.8 and 65.3 months, respectively. Three-year PFS and OS rates were 44% and 72%, respectively; 5-year PFS and OS rates were 30% and 60%, respectively. Intensity-modulated radiation therapy and a maxillary site of origin showed a trend toward superior PFS; higher-dose regimens were associated with somewhat shorter PFS. Relapse was observed in 59% of patients, predominantly local. There were few unanticipated adverse effects, and no grade IV/V events were reported. CONCLUSION: Advanced sinonasal carcinomas are chemoradiosensitive tumors, albeit with a high propensity for local relapse. There is a definite indication for IMRT and a potential curative role of platinum-based chemoradiation regimens. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:855-861, 2017.

Informed consent: do information pamphlets improve post-operative risk-recall in patients undergoing total thyroidectomy: prospective randomized control study.

BACKGROUND: Informed consent consists of basic five elements: voluntarism, capacity, disclosure, understanding, and ultimate decision-making. Physician disclosure, patient understanding, and information retention are all essential in the doctor-patient relationship. This is inclusive of helping patients make and manage their decisions and expectations better and also to deal with any consequences and/or complications that arise. This study investigates whether giving patients procedure-specific handouts pre-operatively as part of the established informed consent process significantly improves overall risk-recall following surgery. These handouts outline the anticipated peri-operative risks and complications associated with total thyroidectomy, as well as the corrective measures to address complications. In addition, the influence of potential confounders affecting risk-recall, such as anxiety and pre-existing memory disturbance, are also examined. METHODS: Consecutive adult (≥18 years old) patients undergoing total thyroidectomy at a single academic tertiary care referral centre are included. Participants are randomly assigned into either the experimental group (with pamphlets) or the control group by a computerized randomization system (Clinstat). All participants filled out a Hospital Anxiety and Depression Scale (HADS) and they are tested by the physician for short-term memory loss using the Memory Impairment Screen (MIS) exam. All patients are evaluated at one week post-operatively. The written recall questionnaire test is also administered during this clinical encounter. RESULTS: Forty-nine patients are included--25 of them receive verbal consent only, while another 24 patients received both verbal consent and patient education information pamphlets. The overall average of correct answers for each group was 83% and 80% in the control and intervention groups, respectively, with no statistically significant differences. There are also no statistically significant differences between the two groups, in both interview duration, in time between interviews, and in recall tests. No correlation is also apparent between the pre-op HADS score and the recall questionnaire overall score. CONCLUSIONS: A pre-operative thyroid surgical information pamphlet alone might not be sufficient to enhance patient test scores and optimally educate the patient on their expected care pathway in thyroid surgery. Supplementation with alternative means of patient education perhaps using emerging technologies needs to be further investigated.

Surgeon performed ultrasound-guided fine-needle aspirates of the thyroid: 1067 biopsies and learning curve in a teaching center.

BACKGROUND: Surgeon performed ultrasound-guided fine-needle aspirates (UG-FNAs) reduce delay in diagnosis and allow for surgeon surveillance. We present the first report on a learning curve and impact of head and neck surgical trainees on adequacy rates. METHODS: Thyroid UG-FNA biopsies from 2009 to 2013 were reviewed retrospectively. Specimen adequacy, cytologic diagnosis, and surgical pathology were used to calculate adequacy and accuracy. RESULTS: One thousand sixty-seven biopsies were examined in 723 individuals. The adequacy rate from adoption into practice improved from 71% to 78% to 85% over 300 cases. When UG-FNA was subsequently taught to trainees, adequacy rates varied among trainees (p < .037), and there were higher nondiagnostic rates earlier in training (p = .04). Adequacy was not related to size or palpability, but cystic lesions yielded more inadequate specimens (p < .001). CONCLUSION: Surgeon performed UG-FNA biopsy can be performed adequately in an outpatient setting. Adequacy rates reach acceptable levels after 300 cases, whereas trainee involvement impacts adequacy rates. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1281-E1284, 2016.

Up-front neck dissection followed by concurrent chemoradiation in patients with regionally advanced head and neck cancer.

BACKGROUND: The appropriate management of the neck in patients with regionally advanced head and neck cancer remains controversial. The purpose of this study was to retrospectively analyze our institutional experience with up-front neck dissection followed by definitive chemoradiotherapy. METHODS: Fifty-five patients with radiographic evidence of large or necrotic lymph nodes underwent up-front neck dissection followed by definitive chemoradiation. RESULTS: The 5-year overall survival (OS) and progression-free survival (PFS) rates were estimated at 71.3% and 64.7%, respectively. There were 2 failures in the dissected neck, for a control rate of 96.7%. There were 7 locoregional failures and 12 distant failures, for locoregional and distant control rates of 87.3% and 78.2%, respectively. CONCLUSION: Up-front neck dissection followed by chemoradiotherapy resulted in excellent locoregional control, OS, and PFS. Utilization of this strategy should be considered in carefully selected patients with regionally advanced head and neck cancer. © 2012 Wiley Periodicals, Inc. Head Neck, 2012.

Factors predictive of severity of osteoradionecrosis of the mandible.

BACKGROUND: An analysis of risk factors predictive of severe mandibular osteoradionecrosis (ORN) is needed to aid prophylaxis and management of this condition. METHODS: We retrospectively analyzed 46 patients diagnosed between June 2002 and March 2009: 93% had mandibular ORN, which was staged 0 to III (Store and Boysen). Patient, tumor, treatment-related, and other variables were analyzed for association with mandibular ORN severity. RESULTS: Oral or oropharyngeal tumors comprised 85% of our primary tumors, 80% were stage IV, and 91% were squamous cell carcinomas. Most patients (87%) received 3-dimensional (3D) conformal radiation therapy (RT), with 60 Gray (Gy) median dose; 28% and 72% received primary and adjuvant RT, respectively; 78% received chemotherapy, mostly concurrent (97%) and platinum-based (96%). Median time to development of ORN was 7.5 months. White ethnicity and secondary infection correlated significantly with stage III mandibular ORN (p = .038, p = .0007, respectively). Advanced age, stage IV, RT dose, post-RT, and lack of pre-RT dental extractions appeared predictive of severe mandibular ORN. CONCLUSIONS: The above-cited factors are predictive of severity and can potentially guide prophylaxis and management.

Intrastriatal serotonin 5-HT2 receptors mediate dopamine D1-induced hyperlocomotion in 6-hydroxydopamine-lesioned rats.

Striatal dopamine (DA) and serotonin (5-HT) functions are altered following DA denervation. Previous research indicates that intrastriatal coadministration of D1 and 5-HT2 receptor agonists synergistically increase locomotor behavior in DA-depleted rats. In the present study, we examined whether striatal 5-HT2 mechanisms also account for supersensitive D1-mediated locomotor behavior following DA denervation. Adult male Sprague-Dawley rats were subjected to bilateral striatal cannulation and then received either intracerebroventricular (i.c.v.) or intrastriatal 6-hydroxydopamine (6-OHDA; 200 microg or 20 microg/side, respectively). After at least 3 weeks, i.c.v.-lesioned rats received intrastriatal infusions of the 5-HT2 receptor antagonist ritanserin (2.0 microg/side) or its vehicle (DMSO) followed by systemic SKF 82958, a D1 agonist (1.0 mg/kg, i.p.) and locomotor activity was monitored. In another experiment, intrastriatal sham and 6-OHDA-lesioned rats received bilateral intrastriatal infusions of ritanserin (2.0 microg/side) or its vehicle (DMSO) followed by intrastriatal infusions of SKF 82958 (5.0 microg/side) or vehicle (0.9% saline). Rats with DA loss demonstrated supersensitive locomotor responses to both systemic and intrastriatal SKF 82958. Ritanserin pretreatment blunted systemic SKF 82958-induced hyperlocomotion and returned intrastriatal D1-mediated hyperactivity to sham lesion levels. The results of this study suggest that striatal 5-HT2 receptors contribute to D1-mediated hyperkinesias resulting from DA loss and suggest a pharmacological target for the alleviation of dyskinesia that can develop with continued DA replacement therapy.