Effect of distance of treatment center on survival for HPV-negative head and neck cancer patients.

BACKGROUND: In rural states, travel burden for complex cancer care required for head and neck squamous cell carcinoma (HNSCC) may affect patient survival, but its impact is unknown. METHODS: Patients with HPV-negative HNSCC were retrospectively identified from a statewide, population-based study. Euclidian distance from the home address to the treatment center was calculated for radiation therapy, surgery, and chemotherapy. Multivariable Cox proportional hazards models were used to examine the risk of 5-year mortality with increasing travel quartiles. RESULTS: There were 936 patients with HPV-negative HNSCC with a mean age of 60. Patients traveled a median distance of 10.2, 11.1, and 10.9 miles to receive radiation therapy, surgery, and chemotherapy, respectively. Patients in the fourth distance quartile were more likely to live in a rural location (p < 0.001) and receive treatment at an academic hospital (p < 0.001). Adjusted overall survival (OS) improved proportionally to distance traveled, with improved OS remaining significant for patients who traveled the furthest for care (third and fourth quartile by distance). Relative to patients in the first quartile, patients in the fourth had a reduced risk of mortality with radiation (HR 0.59, 95% CI 0.42-0.83; p = 0.002), surgery (HR 0.47, 95% CI 0.30-0.75; p = 0.001), and chemotherapy (HR 0.56, 95% CI 0.35-0.91; p = 0.020). CONCLUSION: For patients in this population-based cohort, those traveling greater distances for treatment of HPV-negative HNSCC had improved OS. This analysis suggests that the benefits of coordinated, multidisciplinary care may outweigh the barriers of travel burden for these patients.

A phase 2 study of neoadjuvant chemotherapy plus durvalumab in resectable locally advanced head and neck squamous cell carcinoma.

BACKGROUND: Patients with locally advanced head and neck squamous cell cancer (HNSCC) are treated with surgery followed by adjuvant (chemo) radiotherapy or definitive chemoradiation, but recurrence rates are high. Immune checkpoint blockade improves survival in patients with recurrent/metastatic HNSCC; however, the role of chemo-immunotherapy in the curative setting is not established. METHODS: This phase 2, single-arm, multicenter study evaluated neoadjuvant chemo-immunotherapy with carboplatin, nab-paclitaxel, and durvalumab in patients with resectable locally advanced HNSCC. The primary end point was a hypothesized pathologic complete response rate of 50%. After chemo-immunotherapy and surgical resection, patients received study-defined, pathologic risk adapted adjuvant therapy consisting of either durvalumab alone (low risk), involved field radiation plus weekly cisplatin and durvalumab (intermediate risk), or standard chemoradiation plus durvalumab (high risk). RESULTS: Between December 2017 and November 2021, 39 subjects were enrolled at three centers. Oral cavity was the most common primary site (69%). A total of 35 of 39 subjects underwent planned surgical resection; one subject had a delay in surgery due to treatment-related toxicity. The most common treatment-related adverse events were cytopenias, fatigue, and nausea. Post treatment imaging demonstrated an objective response rate of 57%. Pathologic complete response and major pathologic response were achieved in 29% and 49% of subjects who underwent planned surgery, respectively. The 1-year progression-free survival was 83.8% (95% confidence interval, 67.4%-92.4%). CONCLUSIONS: Neoadjuvant carboplatin, nab-paclitaxel, and durvalumab before surgical resection of HNSCC were safe and feasible. Although the primary end point was not met, encouraging rates of pathologic complete response and clinical to pathologic downstaging were observed.

Osseointegration and Bone Resorption of Scapula Tip Free Flaps in Mandibular Reconstruction.

OBJECTIVES: Bone resorption of more conventional vascularized bone grafts have been well described showing minimal resorption over time. Few studies have evaluated osseous union and bone resorption in scapula tip free flaps (STFF) in the reconstruction of mandibulectomy defects. We aimed to describe our series on STFF with respect to osseous union and bone resorption over time. METHODS: Retrospective chart review of patients receiving STFF from January 2014-January 2017 (n = 25). A neuroradiologist analyzed follow-up CT scans to assess (1) STFF complete, partial, or no osseous union with native mandible and (2) STFF volume change over time in a subset with multiple follow-up scans (n = 18). RESULTS: Twenty-three of 25 patients (92%) showed complete or partial STFF osseous union with native mandible either distally or proximally. STFF volume change ranged from +4.8 to -54% (median -0.5%) over median follow-up interval of 23 months. History of chemoradiation therapy, bisphophonate use, sex, age, or smoking history did not correlate with bone resorption. CONCLUSIONS: STFFs shows high rates of osseous union and limited bone resorption that is equivalent to, or less than, vascularized fibular and iliac crest flaps. Clinically, this translates into both optimal healing and functional and cosmetic outcomes, especially in the setting of prior therapies. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2597-2602, 2023.

Validation of Food Compass with a healthy diet, cardiometabolic health, and mortality among U.S. adults, 1999-2018.

The Food Compass is a nutrient profiling system (NPS) to characterize the healthfulness of diverse foods, beverages and meals. In a nationally representative cohort of 47,999 U.S. adults, we validated a person's individual Food Compass Score (i.FCS), ranging from 1 (least healthful) to 100 (most healthful) based on cumulative scores of items consumed, against: (a) the Healthy Eating Index (HEI) 2015; (b) clinical risk factors and health conditions; and (c) all-cause mortality. Nationally, the mean (SD) of i.FCS was 35.5 (10.9). i.FCS correlated highly with HEI-2015 (R = 0.81). After multivariable-adjustment, each one SD (10.9 point) higher i.FCS associated with more favorable BMI (-0.60 kg/m2 [-0.70,-0.51]), systolic blood pressure (-0.69 mmHg [-0.91,-0.48]), diastolic blood pressure (-0.49 mmHg [-0.66,-0.32]), LDL-C (-2.01 mg/dl [-2.63,-1.40]), HDL-C (1.65 mg/d [1.44,1.85]), HbA1c (-0.02% [-0.03,-0.01]), and fasting plasma glucose (-0.44 mg/dL [-0.74,-0.15]); lower prevalence of metabolic syndrome (OR = 0.85 [0.82,0.88]), CVD (0.92 [0.88,0.96]), cancer (0.95 [0.91,0.99]), and lung disease (0.92 [0.88,0.96]); and higher prevalence of optimal cardiometabolic health (1.24 [1.16,1.32]). i.FCS also associated with lower all-cause mortality (HR = 0.93 [0.89,0.96]). Findings were similar by age, sex, race/ethnicity, education, income, and BMI. These findings support validity of Food Compass as a tool to guide public health and private sector strategies to identify and encourage healthier eating.

Treatment of Localized Amyloid Light Chain Amyloidosis With External Beam Radiation Therapy.

PURPOSE: Localized amyloidosis is a condition characterized by deposits of fibrillary proteins confined to a single organ. The most common subtype is amyloid light chain amyloidosis, which is caused by secretion of amyloidogenic light chain by a monoclonal population of plasma cells. We present a review and discussion of the literature in the context of a case presentation of localized amyloid light chain amyloidosis of the nasopharynx treated with radiation alone. METHODS AND MATERIALS: We reviewed literature relevant to this topic from 1970 to the present. Relevant studies, reports, and articles were summarized in table form. RESULTS: Surgical resection has historically been the primary therapeutic modality for these patients, with radiation being reserved for recurrent lesions or for those unfit for surgery. Although the data are limited to small retrospective series, radiation has been shown to provide good control with mild toxicity that is as good as or better than surgery. Doses range from 20 to 45 Gy, conventionally fractionated. There is no known risk of progression to systemic disease without local therapy. CONCLUSIONS: We recommend local therapy for symptomatic patients after systemic disease has been excluded. We generally recommend radiation in the setting of recurrent lesions, unacceptable toxicity with surgery, poor surgical candidates, and as the initial modality in select patients (elderly individuals with bothersome but nonobstructive lesions).

Reconstruction of oral cavity defects using myogenous-only scapular tip free-flaps.

Background: Oral cavity reconstruction is very challenging anatomical subsite to reconstruct. Large defects often require free tissue reconstruction to provide the best chance of form and function. Additionally, free tissue reconstruction aids to prevent fistula formation. We aimed to determine outcomes of oral cavity defect reconstruction using scapular tip free flaps with a myogenous intraoral component. Methods: All patients with a mandibular or maxillary bony defect that included a disruption of the intraoral mucosa component between 07/1/14 and 07/31/17. Patients were reconstructed with a scapular tip free flap, which included a muscular component that was used to recreate the oral mucosa. The primary study outcomes were flap success rates, development of orocutaneous or oronasal fistula, rate of resuming oral diet as well as the occurrence of medical and surgical complications in the first month following surgery. The tested hypothesis was formulated before data collection began. Results: Twenty-five patients were identified by the study criteria. There was one (4%) flap that failed, while orocutaneous fistula occurred in two patients (8%). Prior history of osteoradionecrosis was a statistically significant predictor of overall complication (p < .05). Conclusions: Intraoral myogenous reconstruction allows for re-mucosalization of the oral cavity defect and is associated with high viability and low-complication rates. In patients with amenable oral mucosal defects, a myogenous scapular tip free flap is a suitable reconstructive option.

Melanoma In Situ of the Hard Palate.

Mucosal melanoma of the oral cavity is rare and highly aggressive, thought to represent less than 1% of melanomas. Within this subgroup, melanoma in situ has been rarely described. We describe the case of a 54-year-old male with history of tobacco use presented with extensive pigmented changes to the hard and soft palate. Biopsy demonstrated melanoma in situ. Mucosal surgical resection was performed with all peripheral epithelial margins involved and negative deep margins. After extensive multidisciplinary discussion, remaining mucosal margins were re-resected to the teeth and posteriorly onto the soft palate. Deep margins remained negative with melanoma in situ still present peripherally. The patient is routinely surveilled without evidence of recurrence. Oral cavity melanoma in situ has been rarely described. The treatment of choice is surgical excision, ranging from wide local excision to composite resections, with consideration given to medical adjuncts. This unique entity should be considered in pigmented oral abnormalities.

The Effect of Multi-Vitamin/Multi-Mineral Supplementation on Nutritional Status in Older Adults Receiving Drug Therapies: A Double-Blind, Placebo-Controlled Trial.

Polypharmacy regimens may increase the susceptibility of older adults to micronutrient inadequacy and deficiency via impairment of nutritional status. We hypothesized that a multi-vitamin-mineral supplement (MVMS) could improve nutritional status in older adults prescribed diuretics, metformin, and/or proton pump inhibitors (PPIs). We conducted a randomized, double-blind, placebo controlled, parallel clinical trial in which eligible subjects were instructed to consume either a MVMS or placebo for 16 wk. Fasting blood was collected at baseline, 8, and 16 wk and the status of selected vitamins and minerals determined. Thirty-five and 19 men and women aged 45-75 yrs in the in MVMS and placebo arms, respectively, completed the trial. The mean total number of medications among the three drug classes taken by participants did not differ between two groups. The status of vitamins B1, B12, C and folate and calcium, copper, magnesium and zinc at baseline were within normal ranges. The MVMS group had a greater change in nutrient status after 16 wk compared to the placebo group for serum folate (7.5 vs. -1.6 ng/mL, p < 0.0001), vitamin B12 (159.2 vs. -33.9 pg/mL, p = 0.007), and plasma vitamin C (0.2 vs. 0.0 mg/dL, p = 0.004). Other measured vitamins and minerals were not significantly changed during the intervention. In conclusion, the status of vitamins B12, C and folate improved with MVMS but remained within normal ranges in older adults taking diuretics, metformin, and/or PPIs.

Near-total mandibular reconstruction following osteoradionecrosis with double scapula tip free flap: A case report.

Near-total mandibular reconstruction poses many challenges to reconstructive surgeons. The purpose of this article is to present a challenging case in a patient with osteoradionecrosis of the mandible requiring a near-total mandibular reconstruction using bilateral scapula tip free tissue reconstruction. A 68-year-old African-American male with a history of T2N0M0 squamous cell carcinoma of the tonsil presented with advanced stage osteoradionecrosis of the mandible. Reconstruction was planned using 3D Systems (Denver, CO), mandibular osteotomies were planned inferior to the sigmoid notch on the ascending rami. Neither fibula flap was amenable for harvesting due to poor vasculature of the patient's lower extremities, and bilateral scapula tip free flaps were subsequently planned. The post-operative course was complicated by venous congestion in the right scapula flap which required revision to the venous anastomosis on POD 1. The patient had intraoral breakdown that required debridement in the operating room and application of a cellular matrix. The patient fully recovered from the acute surgery and was discharged home without a tracheostomy. At the last follow up visit, the patient was taking 100% of diet peroral and had no signs of oral incompetence, mental projection was satisfactory, and the ability to verbally communicate was unimpaired. We report a complex case of near-total mandibular reconstruction using simultaneous bilateral scapula tip free flaps. While we do not advocate simultaneous bilateral scapula tip free flaps as the standard of care for large mandibulectomy defects, it may be considered for patients in which traditional osseous free flaps are not available.

Prognostic impact of socioeconomic status compared to overall stage for HPV-negative head and neck squamous cell carcinoma.

OBJECTIVE: To estimate the relative prognostic ability of socioeconomic status (SES) compared to overall stage for HPV-negative head and neck squamous cell carcinoma (HNSCC) MATERIALS AND METHODS: Data were obtained from the Carolina Head and Neck Cancer Epidemiology Study (CHANCE). An empirical 4-category SES classification system was created. Cox proportional hazards models, survival gradients, Bayesian information criterion (BIC), and Harrell's C index were used to estimate the prognostic ability of SES compared to stage on overall survival (OS). RESULTS: The sample consisted of 1229 patients with HPV-negative HNSCC. Patients with low SES had significantly increased risk of mortality at 5 years compared to patients with high SES (HR 3.11, 95% CI 2.07-4.67; p < 0.001), and the magnitude of effect was similar to overall stage (HR 3.01, 95% CI 2.35-3.86; p < 0.001 for stage IV versus I). Compared to overall stage, the SES classification system had a larger total survival gradient (35.8% vs. 29.1%), similar model fit (BIC statistic of 7412 and 7388, respectively), and similar model discriminatory ability (Harrell's C index of 0.61 and 0.64, respectively). The association between low SES and OS persisted after adjusting for age, sex, race, alcohol, smoking, overall stage, tumor site, and treatment in a multivariable model (HR 2.96, 95% CI 1.92-4.56; p < 0.001). CONCLUSION: SES may have a similar prognostic ability to overall stage for patients with HPV-negative HNSCC. Future research is warranted to validate these findings and identify evidence-based interventions for addressing barriers to care for patients with HNSCC.

Clinical Outcomes of Patients With pT1-T2N0 Oral Tongue Squamous Cell Carcinoma.

OBJECTIVE: The objective of this study was to evaluate the clinical outcomes in a cohort of patients with early-stage oral tongue squamous cell carcinoma (OTSCC). MATERIALS AND METHODS: We conducted a retrospective analysis of patients with pT1-T2N0 (American Joint Committee on Cancer [AJCC] seventh edition) OTSCC treated from 2000 to 2018. Two-year actuarial rates of local regional control, cancer-specific survival, and overall survival were calculated for the entire cohort and patients with/without adjuvant radiation. RESULTS: Ninety-six patients met the criteria with a median follow-up of 4 years; 14 had adjuvant radiation, while 82 had surgery alone. Two-year local regional control was 82.7% (75.4% to 90.8%) for the entire cohort, 84.9% (77.8% to 93.2%) for surgery only, and 70.7% (50.2% to 99.6%) for patients with adjuvant radiation. Two-year progression-free survival was 82.7% (75.3% to 90.8%). Of the 20 patients with recurrence, 11 (55%) were successfully salvaged. CONCLUSION: Local regional recurrence remains modest in early-stage OTSCC, but salvage is possible with high survival rates. LEVEL OF EVIDENCE: Level III-retrospective cohort study.

Socioeconomic Status Drives Racial Disparities in HPV-negative Head and Neck Cancer Outcomes.

OBJECTIVES/HYPOTHESIS: To determine drivers of the racial disparity in stage at diagnosis and overall survival (OS) between black and white patients with HPV-negative head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: Retrospective cohort study. METHODS: Data were examined from of a population-based HNSCC study in North Carolina. Multivariable logistic regression and Cox proportional hazards models were used to assess racial disparities in stage at diagnosis and OS with sequential adjustment sets. RESULTS: A total of 340 black patients and 864 white patients diagnosed with HPV-negative HNSCC were included. In the unadjusted model, black patients had increased odds of advanced T stage at diagnosis (OR 2.0; 95% CI [1.5-2.5]) and worse OS (HR 1.3, 95% CI 1.1-1.6) compared to white patients. After adjusting for age, sex, tumor site, tobacco use, and alcohol use, the racial disparity persisted for advanced T-stage at diagnosis (OR 1.7; 95% CI [1.3-2.3]) and showed a non-significant trend for worse OS (HR 1.1, 95% CI 0.9-1.3). After adding SES to the adjustment set, the association between race and stage at diagnosis was lost (OR: 1.0; 95% CI [0.8-1.5]). Further, black patients had slightly favorable OS compared to white patients (HR 0.8, 95% CI [0.6-1.0]; P = .024). CONCLUSIONS: SES has an important contribution to the racial disparity in stage at diagnosis and OS for HPV-negative HNSCC. Low SES can serve as a target for interventions aimed at mitigating the racial disparities in head and neck cancer. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1301-1309, 2021.

Age and risk of recurrence in oral tongue squamous cell carcinoma: Systematic review.

The incidence of oral tongue squamous cell carcinoma has been increasing in young patients (≤45 years) without a clear etiologic driver. It is unknown if younger patients have an increased risk of recurrence compared to older patients. A literature search was conducted through January 2020 using PubMed/MEDLINE, Embase, Cochrane, Scopus, Science Direct, and clinicaltrials.gov. This review was registered with PROSPERO (ID: CRD42020167498) and the PRISMA statement was followed. Studies were eligible for inclusion if they assessed risk of recurrence by age using a time-to-event analysis, used an age cutoff of ≤45 years or less for the younger cohort, and limited the analysis to the oral tongue subsite. Data were extracted independently by two reviewers using a form with a prespecified list of variables. There were 13 articles that met criteria for the qualitative synthesis (n = 1763 patients). The reported 5-year rates of disease-free survival ranged from 30% to 72% for the younger cohorts and 42% to 81% for the older cohorts. Three studies reported a statistically significant increased risk of recurrence in younger patients, three studies reported a nonsignificant increased risk in younger patients, and seven studies reported a similar risk in younger patients based on the time-to-event analyses. There may be an increased risk of recurrence for younger patients with oral tongue cancer. A definitive conclusion is precluded by limitations among individual studies, and additional research is warranted to examine this question.

Access to preventive care services and stage at diagnosis in head and neck cancer.

BACKGROUND: Decreased access to preventive care services has been proposed as a mechanism for the association between low socioeconomic status (SES) and advanced stage at diagnosis in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Retrospective analysis of patients diagnosed with HNSCC in North Carolina between 2002 and 2006. RESULTS: A total of 1108 patients with HNSCC were included in the study. In the multivariable analysis, use of annual routine dental services (OR 0.7, 95% CI 0.5-0.9) and colonoscopy in the past 10 years (OR 0.7, 95% CI 0.5-0.9) were associated with lower odds of advanced T stage at diagnosis. Having no insurance (OR 1.8, 95% CI 1.1-2.9), an income <$20 000 (OR 1.6 95% CI 1.03-2.6), and >10 pack-years tobacco use (OR 1.5, 95% CI 1.04-2.2) were associated with advanced T stage at diagnosis. CONCLUSION: Use of preventive care services and SES independently predict stage at diagnosis in HNSCC.

Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication.

PURPOSE: Although cisplatin plus radiotherapy is a standard treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC), cisplatin contraindication is common. Radiation elicits and promotes tumor-directed immune stimulation, which may potentiate anti-PD-1 therapy. We provide the first efficacy report of combined pembrolizumab and definitive radiotherapy in LA-HNSCC. PATIENTS AND METHODS: This single-arm, multi-institution, phase II study (NCT02609503) enrolled 29 cisplatin-ineligible patients. Patients received radiotherapy concurrently with three cycles of pembrolizumab 200 mg every 3 weeks followed by three adjuvant cycles. The primary endpoint was a progression-free survival (PFS) of ≥16 months. Correlative studies included peripheral blood flow cytometry and Luminex cytokine profiling. RESULTS: Reasons for cisplatin ineligibility included otopathy (69.0%), nephropathy (20.7%), and neuropathy (6.9%). With median follow-up of 21 months, estimated 24-month PFS and overall survival rates were 71% (95% confidence interval, 49%-84%) and 75% (51%-88%). The primary PFS endpoint has exceeded the hypothesis and its median has not been reached. Toxicities were typical of radiotherapy; however, high rates of grade 3/4 lymphopenia (58.6%) were observed. Flow cytometry revealed a relative decline in CD4 T cells and B cells, but not CD8 T cells. Upon treatment, frequencies of transitional B cells and tissue-like memory B cells increased, while resting memory B cells decreased. Patients with progression had greater percentages of baseline naïve B cells and fewer marginal zone B cells. CONCLUSIONS: Pembrolizumab and radiotherapy is efficacious in LA-HNSCC and should be evaluated in a randomized trial. The observed changes in B-cell markers deserve further study both as potential biomarkers and as therapeutic targets.

Long-term dietary flavonoid intake and risk of Alzheimer disease and related dementias in the Framingham Offspring Cohort.

BACKGROUND: Findings from existing prospective observational studies on the protective associations of flavonoid intake and the risk of Alzheimer disease and related dementias (ADRD) are inconsistent largely due to limitations of these studies. OBJECTIVES: To examine the prospective relation between total and 6 classes of dietary flavonoid intake and risk of ADRD and Alzheimer disease (AD) while addressing limitations of earlier observational studies. METHODS: We used data from the Framingham Heart Study Offspring Cohort exams 5 through 9. Participants were ADRD-free with a valid FFQ at baseline. Flavonoid intakes were updated at each exam to represent the cumulative average intake across the 5 exams, and were expressed as percentile categories of intake (≤15th, >15th to 30th, >30th to 60th, >60th) to handle their nonlinear relation with ADRD and AD. Cox proportional hazards regression was used to estimate the HRs for the association between the flavonoid intakes and incidence of ADRD and AD. RESULTS: Over an average follow-up of 19.7 y in 2801 participants (mean baseline age = 59.1 y; 52% females), there were 193 ADRD events of which 158 were AD. After multivariate and dietary adjustments, individuals with the highest (>60th percentile) intakes of flavonols, anthocyanins, and flavonoid polymers had a lower risk of ADRD relative to individuals with the lowest intakes (≤15th percentile), with HRs (95% CI; P-trend) of 0.54 (0.32, 0.90; P = 0.003) for flavonols, 0.24 (0.15, 0.39; P < 0.001) for anthocyanins, and 0.58 (0.35, 0.94; P = 0.03) for flavonoid polymers. The same pattern of associations was seen with AD for flavonols and anthocyanins but not for flavonoid polymers. CONCLUSIONS: Our findings imply that higher long-term dietary intakes of flavonoids are associated with lower risks of ADRD and AD in US adults.

Flavonoid Intake and MRI Markers of Brain Health in the Framingham Offspring Cohort.

BACKGROUND: Although greater flavonoid intake is associated with a reduced risk of Alzheimer's disease (AD) and related dementias (ADRD), evidence relating dietary flavonoid intake to brain health based on MRI is lacking. OBJECTIVE: The objective of this study was to explore the association between dietary flavonoid intake and MRI measures of brain health, including total brain tissue volume (TBV), white matter hyperintensities volume (WMHV), and hippocampal volume (HV). METHODS: Eligible subjects included members of the Framingham Heart Study Offspring Cohort who were free of stroke at exam 7 and had at least 1 valid food frequency questionnaire from exams 5, 6, or 7 (n = 2086; mean age at exam 7, 60.6 y). Flavonoid intakes represented the cumulative mean of intakes across the 3 exams and were categorized based on quartiles categories of intake. TBV, WMHV, and HV were assessed at exam 7. Multiple linear regression models were used to examine the cross-sectional association between total and the 6 classes of flavonoids and the 3 aforementioned MRI measures. RESULTS: The mean (95% CI) of the WMHV of subjects in the highest quartile category of flavan-3-ols [0.56 (0.52, 0.61)] and flavonoid polymers [0.57 (0.52, 0.61)] intake was significantly smaller relative to that of subjects in the lowest quartile category of flavan-3-ols [0.65 (0.60, 0.71)] and flavonoid polymers [0.66 (0.60, 0.71)] after accounting for important demographic, lifestyle, and clinical factors. Inverse trend associations with WMHV were also seen for flavan-3-ols (P = 0.01) and flavonoid polymers (P = 0.01) as well as for total flavonoids (P = 0.01). TBV and HV were not associated with dietary flavonoid intake following the adjustment for potential confounders. CONCLUSIONS: Our results contribute to the literature on flavonoids and ADRD as they suggest that higher flavonoid intakes may affect ADRD risk in middle-aged and older adults by reducing WMHV, a marker strongly associated with ADRD.

Dietary Supplement Use among Adult Cancer Survivors in the United States.

BACKGROUND: Many cancer patients initiate dietary supplement use after cancer diagnosis. How dietary supplement use contributes to the total nutrient intake among cancer survivors as compared with individuals without cancer needs to be determined. OBJECTIVES: We aimed to evaluate nutrient intakes from dietary supplements among cancer survivors in relation to their total nutrient intake and compare those with individuals without cancer. METHODS: We evaluated the prevalence, dose, and reason for using dietary supplements among 2772 adult cancer survivors and 31,310 individuals without cancer who participated in the NHANES 2003-2016. RESULTS: Cancer survivors reported a higher prevalence of any (70.4% vs. 51.2%) and multivitamin/mineral (48.9% vs. 36.6%) supplement use and supplement use of 11 individual vitamins and 8 minerals than individuals without cancer. Overall, cancer survivors had significantly higher amounts of nutrient intake from supplements but lower nutrient intakes from foods for the majority of the nutrients. Compared with individuals without cancer, cancer survivors had a higher percentage of individuals with inadequate intake (total nutrient intake 

PIK3CA Mutation in HPV-Associated OPSCC Patients Receiving Deintensified Chemoradiation.

PIK3CA is the most frequently mutated gene in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). Prognostic implications of such mutations remain unknown. We sought to elucidate the clinical significance of PIK3CA mutations in HPV-associated OPSCC patients treated with definitive chemoradiation (CRT). Seventy-seven patients with HPV-associated OPSCC were enrolled on two phase II clinical trials of deintensified CRT (60 Gy intensity-modulated radiotherapy with concurrent weekly cisplatin). Targeted next-generation sequencing was performed. Of the 77 patients, nine had disease recurrence (two regional, four distant, three regional and distant). Thirty-four patients had mutation(s) identified; 16 had PIK3CA mutations. Patients with wild-type-PIK3CA had statistically significantly higher 3-year disease-free survival than PIK3CA-mutant patients (93.4%, 95% confidence interval [CI] = 85.0% to 99.9% vs 68.8%, 95% CI = 26.7% to 89.8%; P = .004). On multivariate analysis, PIK3CA mutation was the only variable statistically significantly associated with disease recurrence (hazard ratio = 5.71, 95% CI = 1.53 to 21.3; P = .01). PIK3CA mutation is associated with worse disease-free survival in a prospective cohort of newly diagnosed HPV-associated OPSCC patients treated with deintensified CRT.