Search

PURPOSE/OBJECTIVE(S) Xerostomia is a common sequela of radiation therapy (RT) and chemoradiotherapy (CRT). Head and neck cancer treatment can contribute to salivary glands injury with diminished salivary production and changes in consistency, volume, and pH of saliva. Previous studies examining xerostomia have investigated RT regimens, dosimetric predictors, and quality of life (QoL) associations but few have identified clinicodemographic risk factors for xerostomia and quantified their associations among oropharyngeal carcinoma (OPC) survivors. The objective of this study was to identify risk factors for xerostomia among long-term OPC survivors. MATERIALS/METHODS This was a cross-sectional study conducted at a comprehensive cancer center. Study participants included disease-free, adult OPC survivors who completed curative definitive radiotherapy treatment between January 2000 and December 2013, and responded to a survey administered from September 2015 to July 2016. This study included 881 OPC survivors with a median survival duration at time of survey of 7 years (range, 1-16 years) of which self-reported xerostomia scores were available for 853 participants. The primary outcome variable was patient-reported xerostomia measured using the MD Anderson Symptom Inventory Head and Neck Cancer Module. Clinicodemographic risk factors for moderate to severe xerostomia were identified using multivariable logistic regression. RESULTS Of 853 OPC survivors who responded to the xerostomia question, 337 (39.5%) reported moderate to severe xerostomia. Multivariable logistic regression identified current smoking at time of survey (OR:2.57, 95% CI: 1.20-5.53, P = 0.016) as a risk factor for moderate to severe xerostomia and concurrent cetuximab chemotherapy (OR:0.63; 95% CI: 0.41-0.97, P = 0.038) as a protective factor. Additionally, female sex (OR:1.81, 95% CI: 1.21-2.71, P = 0.004) and less than high school education (OR:1.68, 95% CI: 1.15-2.45, P = 0.008) were risk factors for moderate to severe xerostomia and bilateral intensity modulated radiotherapy (IMRT) combined with proton therapy (OR:0.34, 95% CI: 1.16-0.73, P = 0.005) and ipsilateral IMRT (OR:0.18, 95% CI: 0.07-0.46, P < 0.001) were protective. CONCLUSION In this large xerostomia study, about 4 out of 10 OPC survivors reported moderate to severe xerostomia over long-term follow-up. Continued smoking after cancer diagnosis, sex, and education were identified as important risk factors of moderate to severe xerostomia and concurrent cetuximab therapy and more modern RT regimens had a protective association. Sustained smoking post-diagnosis is a modifiable risk factor which can be addressed with continued smoking cessation efforts. Lastly, these results can inform future research and targeted patient-centered interventions to monitor and manage RT-associated xerostomia and preserve QoL among OPC patients.

Archival tagging studies of southern bluefin tuna (SBT , Thunnus maccoyii) have revealed that juveniles residing in the Great Australian Bight (GAB) over the austral summer undertake seasonal cyclic migrations to the southeast Indian Ocean and the Tasman Sea during winter. However, there remains disagreement about the extent of mixing between juvenile SBT regularly caught by longline fleets south of Africa and those observed in the GAB. Some researchers have argued that archival tag recoveries indicate most juveniles reside in the GAB over the austral summer. Others have suggested that recoveries of conventional and archival tags are better explained by a juvenile population consisting of separate groups on the eastern and western sides of the Indian Ocean with limited intermixing. We present analyses of catch and tag recovery data and re‐examine archival tagging studies. The evidence provided strongly favors the hypothesis of separate juvenile subgroups, or contingents, with limited intermixing. We draw some tentative conclusions about the nature of the putative contingents and discuss some implications of these findings for the interpretation of existing datasets and future research priorities. We also provide the first evidence that the migration choices of juveniles that summer in the GAB are influenced by fidelity to winter feeding grounds and suggest this helps explain the collapse of the surface fishery off New South Wales in the 1980s.

To determine dosimetric parameters associated with osteoradionecrosis (ORN) in oropharyngeal cancer (OPC) patients in the IMRT era.Subsequent to institutional review board approval, we identified ORN in OPC patients treated with IMRT from 2002 to 2013. 1:2 case-control matching was implemented. Mandibular dose-volume histograms (DVH) were extracted. Dosimetric parameters were compared using non-parametric stats. Recursive partitioning analysis (RPA) was done to identify DVH correlates of ORN.68 ORN cases and 131 controls were matched. Median follow-up was 41months and median time to development of ORN was 16months. Mandibular mean dose was significantly higher in the ORN cohort (48.1 vs 43.6Gy, p0.0001). However, the maximum dose was not statistically different. DVH bins from V35 to V73 were all significantly higher in the ORN cohort compared with controls (p0.0006). Two DVH parameters were identified in RPA analysis, V43 and V58. The majority (81%) of ORN cases were observed with both V44≥42% and V58≥25%.Our data demonstrate that a wide range of DVH parameters in the intermediate and high beam path were all significantly higher in ORN patients. Mandibular V4442% and V5825% represent reasonable DVH constraints for IMRT plan acceptability, when tumor coverage is not compromised.

Understanding the growth rates of fish is vital for effective fisheries management. Historically a three-parameter von Bertalanffy growth model (VBGM) has most often been used to describe the somatic growth of fish. However, increasingly, populations are identified with patterns of growth that are not adequately described by the standard VBGM. We describe a more flexible growth model obtained by replacing the normally constant von Bertalanffy growth coefficient, k, with a piecewise constant function, K, of age. In principle this allows arbitrary monotonic growth to be approximated within a generalized von Bertalanffy structure. Posterior distributions of model parameters are approximated by the method of Hamiltonian Monte Carlo using the Stan software package. Spline smoothing of the K function is achieved by specifying a hierarchical random walk prior. We compare fits achieved using this new approach to observations of length-at-age of southern bluefin tuna (Thunnus maccoyii) with a range of existing growth models.

The purpose is to examine the relationship between mandibular osteoradionecrosis (ORN) and chronic dysphagia in long-term oropharynx cancer (OPC) survivors, and to determine the perceived symptom burden associated with ORN.Medical records of 349 OPC patients treated with bilateral IMRT and systemic therapy were reviewed. ORN was graded using a published 4-point classification schema. Patients were considered to have chronic dysphagia if they had aspiration pneumonia, stricture or aspiration detected by fluoroscopy or endoscopy, and/or feeding tube dependence in long-term follow-up ⩾1year following radiotherapy. MD Anderson Symptom Inventory - Head and Neck Module (MDASI-HN) scores were analyzed in a nested cross-sectional survey sample of 118 patients.34 (9.7%, 95% CI: 6.8-13.3%) patients developed ORN and 45 (12.9%, 95% CI: 9.6-16.9%) patients developed chronic dysphagia. Prevalence of chronic dysphagia was significantly higher in ORN cases (12/34, 35%) compared to those who did not develop ORN (33/315, 11%, p0.001). ORN grade was also significantly associated with prevalence of dysphagia (p0.001); the majority of patients with grade 4 ORN requiring major surgery (6 patients, 75%) were found to have chronic dysphagia. Summary MDASI-HN symptom scores did not significantly differ by ORN grade. Significantly higher symptom burden was reported, however, among ORN cases compared to those without ORN for MDASI-HN swallowing (p=0.033), problems with teeth and/or gums (p=0.016) and change in activity (p=0.015) item scores.ORN is associated with excess burden of chronic dysphagia and higher symptom severity related to swallowing, dentition and activity limitations.

This clinical report describes the fabrication of an implant-supported and magnet-retained combination oral-nasal prosthesis for a patient with a midline midfacial defect. The patient had undergone a total rhinectomy and partial maxillectomy as part of his cancer treatment. The nasal prosthesis was retained on the face by a magnet attached to the implant-supported maxillary denture, resulting in improved appearance and the recovery of speech, mastication, and swallowing functions.

Delamination of the maxillofacial silicone elastomer away from the commercially pure titanium (cpTi)-encapsulated magnets affects the long-term performance of the facial restoration.The purposes of this in vitro study were to investigate the interfacial microleakage patterns of 2 maxillofacial silicone elastomers with cpTi when 3 different primers were used and to evaluate the porosity of the 2 elastomers tested.To test the interfacial microleakage patterns of the 2 elastomers MDX4-4210 (EL1) and A-2006 (EL2) with cpTi when 3 metal primers, A-304 (PR1), A-320 bonding enhancer (PR2), Super-Bond CB monomer (PR3), and ethyl-cyanoacrylate (Super Glue) were used, the bonded interfaces were observed using reflected light microscopy, and the percentage of the linear extent of leakage along the interface (%microleakage) was measured. High-resolution x-ray computed microtomography scanning was used to investigate the percentage of void volume fraction (%VF) for both silicone EL1 and EL2. The data were analyzed with 2-way ANOVA and post hoc tests (α=.05).No statistically significant differences were found among the percentages of PR1, PR2, and PR3 microleakage, whereas ethyl-cyanoacrylate showed a statistically significant higher percentage of microleakage than either of the silicone elastomers (P.001). EL1 medical grade elastomer groups have always had a statistically significantly higher percentage of microleakage than the EL2 platinum silicone elastomer groups (P.001). For both elastomers, no statistically significant differences were found in %VF (P=.056).Differences in mechanical properties, chemical composition, and manipulations during handling of the maxillofacial silicone elastomers can affect the linear microleakage along the cpTi-silicone elastomer bonding interface and the porosity of the silicone elastomer.

Background To evaluate and establish a digital workflow for the custom designing and 3D printing of mouth opening tongue-depressing (MOTD) stents for patients receiving radiotherapy for head and neck cancer. Methods We retrospectively identified 3 patients who received radiation therapy (RT) for primary head and neck cancers with MOTD stents. We compared two methods for obtaining the digital impressions of patients’ teeth. The first method involved segmentation from computed tomography (CT) scans, as previously established by our group, and the second method used 3D scanning of the patients’ articulated stone models that were made during the conventional stent fabrication process. Three independent observers repeated the process to obtain digital impressions which provided data to design customized MOTD stents. For each method, we evaluated the time efficiency, dice similarity coefficient (DSC) for reproducibility, and the 3D printed stents’ accuracy. For the 3D scanning method, we evaluated the registration process using manual and automatic approaches. Results For all patients, the 3D scanning method demonstrated a significant advantage over the CT scanning method in terms of time efficiency with over 60% reduction in time consumed (p

Oral oncology/maxillofacial prosthodontics is the branch of dentistry that specializes in the prevention and treatment of the oral morbidities associated with treatment of cancer, as well as the oral prosthetic rehabilitation following tumor ablative surgery. Treatment of cancer in the head and neck can have substantial posttreatment oral morbidities, decreasing the overall quality of life of survivors. Minimizing or reducing these oral challenges becomes increasingly important as the survivability of these cancers improves, particularly those in the oropharynx. Relatively minor interventions, such as pre-treatment oral examination, judicious/strategic dental extractions, patient education, and daily fluoride treatments, can have a dramatic impact in the prevention or reduction of mucositis, osteoradionecrosis, and postradiation dental caries. This chapter will describe practical approaches for the preventing, recognizing, and treating the oral sequelae associated with cancer therapy. This chapter will also describe the most common oral prostheses using after tumor ablative surgery and their indication for use.

The tracheoesophageal puncture (TEP) restores verbal communication after total laryngectomy using a one-way valved voice prosthesis (VP). Microbial colonization can shorten VP device life. Our aims were to investigate patterns of prosthetic and oral colonization, and record changes in VP device life after targeted decontamination. We conducted a retrospective review of TEP clinic patients who underwent microbial analysis of the VP between 01/2003 and 07/2013. Two subgroups were analyzed: (1) patients with microbial analysis of the VP and the mouth were analyzed to identify patterns of common contamination, and (2) patients who were prescribed targeted oral decontamination on the basis of the microbial analysis of the VP were analyzed to evaluate effects on device life. Among 42 patients, 3 patients had only fungal, 5 only bacterial, and 33 had polyspecies fungal and bacterial colonization. In the TEP-oral microflora subgroup (n = 15), 7 had common microorganisms in the mouth and on the VP. Among the decontamination subgroup (n = 23), 6 patients received broad spectrum rinse, 16 antifungal agents and 13 antibiotics, or a combination thereof. After targeted decontamination, the median device life of prostheses improved from 7.89 to 10.82 weeks (p = 0.260). The majority of patients with a suboptimal VP device life in this pilot had polyspecies bacterial and fungal colonization. VPs rarely had fungal contamination alone (3 %), and non-albicans fungal species were more common than expected. For these reasons, we are exploring the use of targeted decontamination regimens that were associated with 1.4-fold improvement in VP duration.

Objectives To investigate the effect of three adhesive primers on the morphology, chemistry and peel bond strength of two maxillofacial silicone elastomers with commercially pure titanium (cpTi). Methods The effect of three primers (PR2:A-304 Primer/A-320 Bonding Enhancer, PR3:Super Bond, and PR4:Super Glue) on cpTi morphology and chemistry were studied by reflected light polarized microscopy (RPOLM) and reflection Fourier-transform infrared microspectroscopy (RFTIRM). For testing the bond strength between two elastomers (EL1:MDX4-4210, EL2:A-2006) and primed cpTi surfaces, a 90° T peel test was performed (PBS), using as reference EL1, EL2 specimens bonded to heat-cured poly(methyl methacrylate) resin (PMMA) primed with A-330G primer (PR1). Failure modes were analyzed under a stereomicroscope, and the percentage of remaining silicone (RS%) on cpTi and PMMA were calculated by image analysis. Scanning electron microscopy/energy dispersive X-ray spectrometry (SEM/EDX) was used to investigate representative failure patterns on cpTi. Data were analyzed with Weibull analysis, ANOVA plus post hoc tests, and Pearson correlation coefficient ( a = 0.05). Results Thick-irregular (PR2), thin-smooth (PR3), and uniform-porous (PR4) films were identified on cpTi by RPOLM. RFTIRM revealed: a strong peak of Si–O–Si with a distribution following the outline of the image (PR2); COO-M groups developed, but unevenly distributed (PR3); and reduction in C C groups due to in situ polymerization (PR4). Following PBS, the ranking of the statistical significant differences in Weibull scale parameter ( σ 0 ) of the EL1 group was PMMA_PR1 > cpTi_PR2,cpTi_PR3 > cpTi_PR4, whereas for the EL2 group cpTi_PR2 > PMMA_PR1 > cpTi_PR4,cpTi_PR3. For RS%, the ranking in the EL1 group was: PMMA_PR1 > cpTi_PR2 > cpTi_PR3 > cpTi_PR4, and in the EL2 cpTi_PR2 > cpTi_PR3 > cpTi_PR4,PMMA_PR1. There was no statistically significant correlation between PBS and RS%, with the exception of EL1_PMMA_PR1. In all groups mixed failure modes were found by SEM/EDX. Significance Although there is evidence of bonding with cpTi, there are important differences among the primer/elastomer combination that may affect the clinical performance of these materials.

Customized intraoral devices help the radiation oncologist minimize the adverse effects of radiation and maximize the tumor control rate by keeping the anatomic structures in a consistent position during each fraction of radiation treatment. This article illustrates the fabrication of a bolus-type positioning device for a combined intraoral/extraoral defect treated with proton radiation therapy.

Background and purpose Customized mouth-opening-tongue-depressing-stents (MOTDs) may reduce toxicity in patients with head and neck cancers (HNC) receiving radiotherapy (RT). However, making MOTDs requires substantial resources, which limits their utilization. Previously, we described a workflow for fabricating customized 3D-printed MOTDs. This study reports the results of a prospective trial testing the non-inferiority of 3D-printed to standard and commercially-available (TruGuard) MOTDs as measured by patient reported outcomes (PROs). Materials and methods PROs were collected at 3 time points: (t1) simulation, (t2) prior to RT, (t3) between fractions 15–25 of RT. Study participants received a 3D-printed MOTDs (t1, t2, t3), a wax-pattern (t1), an acrylic-MOTDs (t2, t3) and an optional TruGuard (t1, t2, t3). Patients inserted the stents for 5–10 min and completed a PRO-questionnaire covering ease-of-insertion and removal, gagging, jaw-pain, roughness and stability. Inter-incisal opening and tongue-displacement were recorded. With 39 patients, we estimated 90% power to detect a non-inferiority margin of 2 at a significance level of 0.025. Matched pairs and t-test were used for statistics. Results 41 patients were evaluable. The 3D-printed MOTDs achieved a significantly better overall PRO score compared to the wax-stent (p = 0.0007) and standard-stent (p = 0.0002), but was not significantly different from the TruGuard (p = 0.41). There was no difference between 3D-printed and standard MOTDs in terms of inter-incisal opening (p = 0.4) and position reproducibility (p = 0.98). The average 3D-printed MOTDs turn-around time was 8 vs 48 h for the standard-stent. Conclusions 3D-printed stents demonstrated non-inferior PROs compared to TruGuard and standard-stents. Our 3D-printing process may expand utilization of MOTDs.

Purpose This observational case registry study was designed to describe the natural history of cancer patients with medication-related osteonecrosis of the jaw (ONJ) and evaluate the ONJ resolution rate. Methods Adults with a diagnosis of cancer and with a new diagnosis of ONJ were enrolled and evaluated by a dental specialist at baseline and every 3 months for 2 years and then every 6 months for 3 years until death, consent withdrawal, or loss to follow-up. The primary endpoint was the rate and time course of ONJ resolution. Secondary endpoints included frequency of incident ONJ risk factors, ONJ treatment patterns, and treatment patterns of antiresorptive agents for subsequent ONJ. Results Overall, 327 patients were enrolled; 207 (63%) were continuing on study at data cutoff. Up to 69% of evaluable patients with ONJ had resolution or improvement during the study. ONJ resolution (AAOMS ONJ staging criteria) was observed in 114 patients (35%); median (interquartile range) time from ONJ onset to resolution was 7.3 (4.5–11.4) months. Most patients (97%) had received antiresorptive medication before ONJ development, 9 patients (3%) had not; 68% had received zoledronic acid, 38% had received denosumab, and 10% had received pamidronate (56% had received bisphosphonates only, 18% had received denosumab only, and 21% had exposure to both). Conclusions These results are consistent with those observed in clinical trials evaluating skeletal-related events in patients with advanced malignancy involving bone. Longer follow-up will provide further information on ONJ recurrence and resolution rates between medically and surgically managed patients.

This report describes a case of osteonecrosis of the jaw developing after a routine dental extraction in a patient being treated with dasatinib, a tyrosine kinase inhibitor, for chronic myelogenous leukemia. As the role of tyrosine kinase inhibitors in cancer treatment expands, patterns of debilitating complications involving the osseous structures of the oral cavity have begun to emerge, and many long-term side effects of this promising therapy remain unknown. To limit the occurrence of known complications, health care providers and patients must be aware of the potential for serious complications of dasatinib, and appropriate protocols should be in place before administration of this medication.

The purpose of this study is to estimate the prevalence and severity of late oral morbidities in disease-free oropharyngeal cancer (OPC) survivors using patient reported outcomes.Cross-sectional survivorship survey of patients who completed definitive treatment for oropharyngeal carcinoma 12-months previously without evidence of recurrence, second primary malignancy, or distant metastasis after index cancer. Using MD Anderson Symptom Inventory- Head and Neck Module (MDASI-HN), scores for 4 self-reported oral morbidities: dry mouth, mucus secretions, mouth and throat sores, and teeth and gum issues were evaluated.Among 906 survey respondents (57% response rate), (median survival time: 7 years), "dry mouth" and "problems with my mucus" were reported moderate/severe (MDASI-HN item score ≥5) in 39% and 22% of respondents, while 14% reported moderate/severe "problems with teeth and gums". Smoking at the time of survey was significantly associated with the severity of oral symptoms including "mucus" (p = 0.03), "dry mouth" (p = 0.02), "problems with my teeth and gums" (p = 0.001). All the oral morbidities symptom items significantly, positively correlated with the mean interference scores reflecting adverse impact to quality of life (QOL): "mucus" (r = 0.445, p 0.001), "problems with teeth" (r = 0.446, p 0.001), "mouth sores" (r = 0.321, p 0.001) and "dry mouth" (r = 0.459, p 0.001).This study showed that 45.5% reported at least one late oral morbidity at moderate/severe level which negatively correlated overall function, even years after treatment.

The complete or partial loss of an ear can have a negative impact on self-esteem, and physical disfigurement can impair social integration. An auricular prosthesis can replace the absent or partially absent ear resulting from tumor ablation, infection, congenital defect, or trauma. This chapter briefly describes considerations in fabricating an auricular prosthesis as well as case presentations to support the benefit of a prosthetic ear compared to soft tissue reconstruction.

GABA

Background Dental restoration is an integral part of head and neck cancer reconstruction. Methods We evaluated the success rate of osseointegrated implants in patients with head and neck cancer, comparing outcomes between implants placed in fibula free flaps to those placed in native mandibular and maxillary bone. Results A total of 1132 implants were placed in 246 patients. The overall implant loss rate was 3.7% and was higher in fibula flaps (8.2%) compared to the native mandible (2.6%) and maxilla (2.2%), although these differences did not reach statistical significance (p = .059 and p = .053, respectively). The failure rate was 8.0% for implants placed after radiation and 3.6% in patients who did not undergo radiation (p = .097). Osteoradionecrosis (ORN) occurred in 19 patients (7.7%) after implant placement, and tobacco use was found to be a risk factor (p = .027). Conclusion Osseointegrated implants are reliable in patients with head and neck cancer, including those undergoing bony free flap reconstruction. © 2015 Wiley Periodicals, Inc. Head Neck 38: E321–E327, 2016

Double tagging studies are used to estimate the proportion of originally tagged fish that shed their tags prior to recapture, but models typically fitted to double tag recoveries have been subject to restrictive assumptions. For example, a common assumption is that the shedding rates of all tags are identical. Hearn et al. (Hearn, W.S., Leigh, G.M., Beverton, R.J.H., 1991. ICES J. Mar. Sci. 48, 41–51) found differences in shedding rates between taggers, and demonstrated algebraically that such differences lead to biases in estimators of shedding rates. However, widely applicable models that account for differences in shedding rates between taggers have not been developed. We adapt the proportional hazards model to the problem of estimating tag shedding rates from double-tag recovery data. Differences in shedding rates between taggers are modelled using multiplicative random effects or frailties. The frailty models are fitted to recoveries from a 1990s tagging study of southern bluefin tuna ( Thunnus maccoyii ) at exact times-at-liberty and the results compared with models previously applied for this species.

Background Oral stents have been shown to reduce the deleterious effects of head and neck radiotherapy through the displacement of normal tissues away from the areas of high dose irradiation. While these stents are commonly used in the treatment of patients with head and neck cancer at many large academic cancer centers, their use is much more limited outside of these institutions due to the time and expertise required for their fabrication. Results In the study, we describe a novel method to design and manufacture oral stents from routine computed tomography (CT) imaging studies through the use of 3D printing technologies. Conclusion Our proposed method may help to greatly expand access to these beneficial devices for patients undergoing radiation treatment at centers without access to dental and oral/maxillofacial specialists.

Patients with metastatic breast cancer may develop oral morbidities that result from therapeutic interventions. Mammalian target of rapamycin (mTOR) inhibitor-associated stomatitis (mIAS) is a common adverse event (AE), secondary to mTOR inhibitor therapy, that can have a negative impact on treatment adherence, quality of life, and health care costs. A multidisciplinary team approach is important to minimize mIAS and to maximize treatment benefits to patients with breast cancer. In this review, we discuss the pathophysiology, diagnosis, and natural history of mIAS. Current and new management strategies for the prevention and treatment of mIAS are described in the context of fostering a coordinated team care approach to optimizing patient care.The authors conducted a PubMed search from 2007 through 2017 using the terms "stomatitis," "mIAS," "everolimus," "mTOR," "metastatic breast cancer," and "oral care." They selected articles published in peer-reviewed journals that reported controlled trials and evidence-based guidelines.mIAS can be distinguished from mucositis caused by cytotoxic chemotherapy or radiotherapy on the basis of cause, clinical presentation, and treatment paradigms. Specific preventive and therapeutic management strategies can be implemented across the continuum of patient oral health care.Oral health care providers are on the frontline of oral health care for patients with metastatic breast cancer and are uniquely positioned to provide patient education, advocate accurate reporting of mIAS, and support early identification, monitoring, and prompt intervention to mitigate the severity and duration of this manageable, potentially dose-limiting AE.

Summary Background Stomatitis is a class effect associated with the inhibition of mTOR and is associated with everolimus therapy for breast cancer. Topical steroids might reduce stomatitis incidence and severity, and the need for dose reductions and interruptions of everolimus. Anecdotal use of topical steroid oral prophylaxis has been reported in patients with breast cancer. We aimed to assess dexamethasone-based mouthwash for prevention of stomatitis in patients with breast cancer. Methods This US-based, multicentre, single-arm, phase 2 prevention study enrolled women aged 18 years and older with postmenopausal status who had histologically or cytologically confirmed metastatic hormone receptor-positive, HER2-negative breast cancer. Beginning on day 1 of cycle 1, patients received everolimus 10 mg plus exemestane 25 mg daily, with 10 mL of alcohol-free dexamethasone 0·5 mg per 5 mL oral solution (swish for 2 min and spit, four times daily for 8 weeks). After 8 weeks, dexamethasone mouthwash could be continued for up to eight additional weeks at the discretion of the clinician and patient. The primary endpoint was incidence of grade 2 or worse stomatitis by 8 weeks assessed in the full analysis set (patients who received at least one dose of everolimus and exemestane and at least one confirmed dose of dexamethasone mouthwash) versus historical controls from the BOLERO-2 trial (everolimus and exemestane treatment in patients with hormone receptor-positive advanced breast cancer who were not given dexamethasone mouthwash for prevention of stomatitis). This trial is registered at ClinicalTrials.gov, number NCT02069093. Findings Between May 28, 2014, and Oct 8, 2015, we enrolled 92 women; 85 were evaluable for efficacy. By 8 weeks, the incidence of grade 2 or worse stomatitis was two (2%) of 85 patients (95% CI 0·29–8·24), versus 159 (33%) of 482 patients (95% CI 28·8–37·4) for the duration of the BOLERO-2 study. Overall, 83 (90%) of 92 patients had at least one adverse event. The most frequently reported grade 3 and 4 adverse events in the safety set were hyperglycaemia (seven [8%] of 92 patients), rash (four [4%]), and dyspnoea (three [3%]). Serious adverse events were reported in 20 (22%) patients; six (7%) were deemed treatment related, with dyspnoea (three [3%]) and pneumonia (two [2%]) reported most frequently. 12 (13%) of 92 patients had adverse events suspected to be related to treatment that led to discontinuation of everolimus and exemestane (the most common were rash, hyperglycaemia, and stomatitis, which each affected two [2%] patients). Interpretation Prophylactic use of dexamethasone oral solution substantially reduced the incidence and severity of stomatitis in patients receiving everolimus and exemestane and could be a new standard of oral care for patients receiving everolimus and exemestane therapy. Funding Novartis Pharmaceuticals Corporation.

Background Jaw complications, including osteoradionecrosis, are significant sequelae of radiation therapy (RT) for oral cancers. This study identifies the impact of patient, tumor, and treatment characteristics on the development of jaw complications in patients treated with RT. Methods The Surveillance, Epidemiology, and End Results (SEER)–Medicare database was used to identify patients treated with RT for oral cancers from 1999 to 2007. Jaw complications were identified by International Classification of Diseases 9th revision (ICD-9) diagnosis codes and/or related procedures using Current Procedural Terminology (CPT) and ICD-9 codes. Results A total of 1848 patients were identified. With a median follow-up of 2.5 years, 297 patients (16.1%) developed jaw complications: 226 patients had a diagnosis, 41 patients had a procedure, and 30 patients had both. On multivariate analysis, female sex, lack of chemotherapy use, and fewer comorbidities were associated with a statistically significant increase in jaw complications. Conclusions Even with modern techniques, jaw complications are a notable and potentially devastating side effect of RT for oral cancers. © 2012 Wiley Periodicals, Inc. Head Neck, 35: 1599–1605, 2013

To examine practices of dentists in Texas providing dental/oral care to cancer patients.Dental providers in Texas were invited via email to participate in an exploratory cross-sectional study. A non-probability voluntary convenience sampling procedure was used to recruit the sample. The online, anonymous, self-reported survey included questions to capture demographics, type of dental practice, services provided, and number of cancer patients. The study was approved by the Institutional Review Board of The university of Texas MD Anderson Cancer Center.A total of 655 dentists completed the questionnaire items. Results revealed that 62% of the respondents were 51-65 years old, predominantly (68%) male, Caucasian (81%) with their dental degrees awarded in the state of Texas (77%). 91% of the dentists provide dental care to patients who are currently undergoing cancer treatment or have a history of cancer. However, 80% of the dental providers do not teach oral self-exam to their patients, which may include cancer survivors or those undergoing cancer treatment, while 32% dentists do not deliver brief interventions for effectively motivating and assisting tobacco users to quit.Because Texas, especially Houston, is known for world-class cancer care, dentists in the state are more likely to provide dental care to oncologic patients, especially emergency dental procedures in cancer patients facing some of the side effects of cancer treatment. Careful monitoring of oral health and reducing tobacco use are especially important during and after cancer therapy to prevent, detect, and treat complications as soon as possible. A further step in oral care for cancer patients and survivors is to train patients how to perform regular oral self-examination and to provide tobacco users with cessation counseling as part of their dental/oral treatment. These simple but comprehensive approaches, along with regular dental visits, will positively impact the health-related outcomes for cancer patients, enhancing both survival and quality of life.

We compared mandibular doses and osteoradionecrosis in patients with oropharyngeal cancer after intensity-modulated radiation therapy (IMRT) or intensity-modulated proton therapy (IMPT).We identified 584 patients who received definitive radiotherapy for oropharyngeal cancer from January 2011 through June 2014 at MD Anderson Cancer Center (534 IMRT and 50 IMPT). The dosimetric variables and osteoradionecrosis were compared with Chi-square test or Fisher's exact test.Median follow-up time for all patients (534 IMRT and IMPT) was 33.8months (33.8months IMRT vs. 34.6months IMPT, P=0.854), and median time to osteoradionecrosis was 11.4months (range 6.74-16.1months). Mandibular doses were lower for patients treated with IMPT (minimum 0.8 vs. 7.3Gy; mean 25.6 vs. 41.2Gy; P0.001), and osteoradionecrosis rates were lower as well: 2% IMPT (1 grade 1), 7.7% IMRT (12 grade 4, 5 grade 3, 1 grade 2 and 23 grade 1). Osteoradionecrosis location depended on the primary tumor site and high-dose field in the mandible.Osteoradionecrosis events were significantly associated with higher dose irradiation to mandibular. Use of IMPT minimized excess irradiation of the mandible and consequently reduced the risk of osteoradionecrosis for oropharyngeal cancer.

Normal tissue toxicity is an important consideration in the continued development of more effective external beam radiotherapy (EBRT) regimens for head and neck tumors. The ability to detect EBRT-induced changes in mandibular bone vascularity represents a crucial step in decreasing potential toxicity. To date, no imaging modality has been shown to detect changes in bone vascularity in real time during treatment. Based on our institutional experience with multi-parametric MRI, we hypothesized that DCE-MRI can provide in-treatment information regarding EBRT-induced changes in mandibular vascularity. Thirty-two patients undergoing EBRT treatment for head and neck cancer were prospectively imaged prior to, mid-course and following treatment. DCE-MRI scans were co-registered to dosimetric maps to correlate EBRT dose and change in mandibular bone vascularity as measured by Ktrans and Ve. DCE-MRI was able to detect dose-dependent changes in both Ktrans and Ve in a subset of patients. One patient who developed ORN during the study period demonstrated decreases in Ktrans and Ve following treatment completion. We demonstrate, in a prospective imaging trial, that DCE-MRI can detect dose-dependent alterations in mandibular bone vascularity during chemoradiotherapy, providing biomarkers that are physiological correlates of acute of acute mandibular vascular injury and recovery temporal kinetics.

Osteonecrosis of the jaws has recently been associated with HIV infection and requires surgical and prosthetic intervention. The prosthetic management of an HIV patient with a maxillary lesion, as well as medical status-related treatment considerations, are discussed in this article.

Treatments for head and neck squamous cell carcinoma (HNSCC) are associated with toxicities that lead to emergency department presentation.We utilized data from an ongoing prospective cohort of newly diagnosed, previously untreated patients (N = 298) with HNSCC to evaluate the association between clinical and epidemiologic factors and risk for and frequency of emergency department presentation. Time to event was calculated from the date of treatment initiation to emergency department presentation, date of death, or current date. Frequency of emergency department presentation was the sum of emergency department visits during the follow-up time.History of hypertension, normal/underweight body mass index (BMI), and probable depression predicted increased risk for emergency department presentation. BMI and severe pain were associated with higher frequency of emergency department presentations.Clinical and epidemiologic factors can help predict patients with HNSCC who will present to the emergency department. Such knowledge may improve treatment-related patient outcomes and quality of life. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1195-1204, 2017.

Summary Purpose The present study was undertaken to evaluate osteoradionecrosis (ORN) in patients with salivary gland malignancies (SGM) after treatment with radiation therapy. Materials and methods The medical records of 172 patients treated with radiation therapy for SGM during a 12-year period (August 2001 to November 2013) were reviewed. Incidence, time to event, staging and management of ORN were analyzed. Results Of the 172 patients, 7 patients (4%) developed ORN (median latency: 19 months, range: 4–72 months). Of those 7 patients, 4 required major surgery, 1 required hyperbaric oxygen therapy (HBO), one required minor debridement, and one required conservative management. Total prescribed radiation dose varied from 50 Gy (1 case) to 70 Gy (1 case) among those patients who developed ORN, and radiotherapy was delivered postoperatively after osseous resection in 4 of 7 cases. Three of the 7 cases of ORN occurred after traumatic injury to the bone. Of the 7 patients who developed ORN, 3 had SGM of the major glands, 3 had other sites of the oral cavity, and 1 had a sinonasal location. Conclusion While the rate of ORN after radiotherapy for SGM was somewhat lower (4%) than previously published data on patients with squamous cell carcinomas of the head and neck treated with radiation therapy (8–14%), ORN necessitating major surgery remains a clinically significant, possible late effect of radiotherapy in SGM survivors. Location of SGM is very important, with cases that developed ORN disproportionally having primary disease arising in the oral cavity.

Purpose: To determine the disease control rate and toxicity of treating patients with aggressive cutaneous squamous cell carcinoma (CSCC) with neoadjuvant gefitinib. Experimental Design: A prospective phase II clinical trial evaluating neoadjuvant gefitinib given prior to standard treatment with surgery and/or radiotherapy. Patients with stable disease after one cycle received escalated doses. Patients who responded were given gefitinib during radiation therapy, as well as maintenance therapy after definitive treatment. We analyzed the correlation between epidermal growth factor receptor (EGFR) expression, mutation status, and gene copy number on available tissue samples and clinical response. Results: Twenty-three patients were accrued and 22 patients were evaluable for response prior to definitive local treatment; complete responses were attained by 18.2% of patients and partial responses by 27.3%. Grades 2 to 3 toxicities were observed in 59.1% of patients experiencing class-specific effects during induction therapy. After induction, 11.8% underwent surgery alone, 17.6% had definitive radiation, 11.8% were treated with radiation and concurrent gefitinib, and 47% had surgery with postoperative radiation and concurrent gefitinib. Median follow-up for the censored observations was 32 months. Two-year overall, disease-specific, and progression-free survival rates were 72.1%, 72.1%, and 63.6%, respectively. No EGFR-activating mutations were identified in tumor samples available from 10 patients. No associations between EGFR correlative studies and patient outcomes were identified. Conclusions: Gefitinib, in the neoadjuvant setting, was active and well tolerated in patients with aggressive CSCC and did not interfere with definitive treatment. In view of the 18% complete response rate we observed, EGFR tyrosine kinase inhibitors should be further explored in the treatment of aggressive CSCC. Clin Cancer Res; 18(5); 1435–46. ©2012 AACR.

Background We assessed the effectiveness of cevimeline 30 mg 3 times daily in patient-reported oral health (Oral Health Impact Profile [OHIP-49]) and quality of life (QOL) in patients with xerostomia. Methods In our investigator-initiated, multicenter, randomized, double-blind, placebo-controlled study, patients who received >40 Gy of radiation therapy to the head and neck including at least 3 major salivary glands were randomized to cevimeline 30 mg or placebo orally 3 times daily for 6 weeks. Patients had to have grade 1 or 2 xerostomia and be >16 weeks posttreatment. Clinical data were collected and questionnaires administered at baseline and week 6. The primary outcome was change in OHIP-49 total score from baseline to week 6. Results No statistically significant differences in oral health or QOL were observed. During the 6 weeks of the study, the severity of xerostomia decreased from baseline. Conclusions Xerostomia is a significant sequela of treatment of head and neck cancer that may improve with time. The role of oral parasympathetic muscarinic secretogogues in alleviating patient symptoms and complaints remains unclear. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Background Xerostomia (dry mouth) after head/neck radiation is a common problem among cancer patients and available treatments are of little benefit. The objective of this trial was to determine if acupuncture can prevent xerostomia among head/neck patients undergoing radiotherapy.

Changes in the epidemiology of head and neck cancers have resulted in an increasing number of younger and healthier patients being treated with definitive external beam radiotherapy (EBRT). The long-term consequences of radiotherapy in a patient population with good clinical outcomes and extended life expectancy are becoming increasingly relevant in the management of treatment-associated morbidity and mortality. Osteoradionecrosis (ORN) of the mandible is a challenging issue related to irradiation, occurring in up to 16% of patients with various types of head and neck cancers. Altered bone vascularity and opportunistic infections within the oral cavity contribute to the development of ORN, leading to an inexorable process of bone destruction that does not follow the normal sequence of healing events. Early-stage ORN is often managed using antibiotics, local wound care, and hyperbaric oxygen (HBO). Advanced ORN requires surgical resection and reconstruction with healthy nonirradiated tissue. Successful management of this disease process requires an enhanced ability to identify patients at risk for ORN, monitor the effectiveness of conservative management, and improve preoperative planning to ensure clear margins at the time of resection. However, a standardized, objective staging and monitoring system for ORN is not currently available. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a clinically available quantitative imaging method that is increasingly employed to assess microvascular function in the study of solid tumors of the head and neck. At our institution, DCE-MRI is integrated into a multimodality clinical algorithm aimed at improving the diagnosis, staging, and oncologic surveillance of head and neck tumors. DCE-MRI can detect altered bone vascularity associated with bone healing, necrosis, and metastatic involvement, with excellent spatial resolution. We hypothesize that DCE-MRI can be used to detect alterations in bone vascularity following irradiation to monitor ORN clinical progression and response to treatment. We are evaluating the potential of DCE-MRI to identify patients at risk for mandibular ORN, monitor response to conservative management, and determine the extent of advanced mandibular ORN to assist in surgical planning. This work has the potential to revolutionize the diagnosis and management of mandibular ORN. For the first time, clinicians will be able to identify patients at risk for ORN and manage post-radiotherapy care appropriately. The effectiveness of currently employed conservative measures could be tested using an objective measure and improved preoperative planning could reduce the rate of surgical failure due to residual compromised bone. Citation Format: Vlad C. Sandulache, Abdallah S.R. Mohamed, Yunyun Chen, Katherine A. Hutcheson, Brian P. Hobbs, Mark S. Chambers, Jason M. Johnson, Michelle D. Williams, James A. Bankson, Clifton D. Fuller, Stephen Y. Lai. Optimizing head and neck cancer treatment outcomes with MRI [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr IA14.

Tracheoesophageal (TE) speech using a voice prosthesis and hands-free speaking valve with an intraluminal attachment is the gold standard for voice restoration after total laryngectomy. Modification of a standard self-retaining silicone cannula or laryngectomy button often aids in the attachment of a speaking valve within the tracheal lumen for hands-free TE speech production. An increased number of laryngectomized individuals are able to achieve hands-free TE speech when the standard length, flange, and diameter of a silicone button is customized to accommodate individual tracheostomal contours. A technique is presented for modification of a standard silicone laryngectomy button to facilitate hands-free TE speech after total laryngectomy. (J Prosthet Dent 2009;102:328-331)

Background This pilot study evaluated if acupuncture can alleviate radiation-induced xerostomia among patients with cancer. Secondary objectives were to assess the effects of acupuncture on salivary flow and quality of life (QOL). Methods Nineteen patients received acupuncture twice a week for 4 weeks. Results Xerostomia inventory (XI) and patient benefit questionnaire (PBQ) scores were significantly better after acupuncture on weeks 4 and 8 than at baseline (XI: p = .0004 and .0001; PBQ: p = .0004 and .0011, respectively). For QOL at weeks 4 and 8, there was a significant difference for questions related to head/neck cancer (p = .04 and .006, respectively). At week 8, there was a significant difference in physical well-being (p = .04). At weeks 5 and 8, there were significant differences in the total score (p = .04 and .03, respectively). Conclusions Acupuncture was effective for radiation-induced xerostomia in this small pilot study. Further research is needed. © 2009 Wiley Periodicals, Inc. Head Neck, 2009

Purpose The present study was undertaken to evaluate our recent experience with mandibular osteoradionecrosis (ORN) and to identify factors that contribute to its progress. Patients and Methods The medical records of 114 patients who had been treated for ORN during a 16-year period (1989 to 2004) were reviewed. The patients were then divided into 2 groups according to their response to conservative treatment. Group 1 consisted of patients whose ORN resolved with conservative treatment (n = 47). Group 2 consisted of patients whose ORN was unresolved with conservative treatment or who had required radical resection of the involved tissue (n = 67). The information was obtained from the medical records of the patients and analyzed. Results The patients whose ORN was associated with an early-stage tumor or preirradiation extraction had a favorable response to conservative treatment. However, those who had an advanced primary tumor, had continued smoking and drinking after radiotherapy, had received palliative radiotherapy or a radiation dose of more than 6,000 rads, and who had an orocutaneous fistula, a pathologic fracture, swelling, or trismus had a poor response to conservative treatment. In these latter cases, radical resection of the involved tissue proved useful. Conclusions The results of the present study have indicated that several factors (ie, the stage of the primary tumor, signs of ORN) can influence the progress of ORN. Our results suggest that radical resection is a useful method for treating mandibular ORN that does not respond to conservative treatment.

Purpose To compare the M. D. Anderson Symptom Inventory–Head and Neck (MDASI-HN) module, a symptom burden instrument, with the Functional Assessment of Cancer Therapy–Head and Neck (FACT-HN) module, a quality-of-life instrument, for the assessment of mucositis in patients with head-and-neck cancer treated with radiotherapy and to identify the most distressing symptoms from the patient's perspective. Methods and Materials Consecutive patients with head-and-neck cancer ( n = 134) completed the MDASI-HN and FACT-HN before radiotherapy (time 1) and after 6 weeks of radiotherapy or chemoradiotherapy (time 2). The mean global and subscale scores for each instrument were compared with the objective mucositis scores determined from the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0. Results The global and subscale scores for each instrument showed highly significant changes from time 1 to time 2 and a significant correlation with the objective mucositis scores at time 2. Only the MDASI scores, however, were significant predictors of objective Common Terminology Criteria for Adverse Events mucositis scores on multivariate regression analysis (standardized regression coefficient, 0.355 for the global score and 0.310 for the head-and-neck cancer-specific score). Most of the moderate and severe symptoms associated with mucositis as identified on the MDASI-HN are not present on the FACT-HN. Conclusion Both the MDASI-HN and FACT-HN modules can predict the mucositis scores. However, the MDASI-HN, a symptom burden instrument, was more closely associated with the severity of radiation-induced mucositis than the FACT-HN on multivariate regression analysis. This greater association was most likely related to the inclusion of a greater number of face-valid mucositis-related items in the MDASI-HN compared with the FACT-HN.