Consensuses, controversies, and future directions in treatment deintensification for human papillomavirus-associated oropharyngeal cancer.

The most common cancer caused by human papillomavirus (HPV) infection in the United States is oropharyngeal cancer (OPC), and its incidence has been rising since the turn of the century. Because of substantial long-term morbidities with chemoradiation and the favorable prognosis of HPV-positive OPC, identifying the optimal deintensification strategy for this group has been a keystone of academic head-and-neck surgery, radiation oncology, and medical oncology for over the past decade. However, the first generation of randomized chemotherapy deintensification trials failed to change the standard of care, triggering concern over the feasibility of de-escalation. National database studies estimate that up to one third of patients receive nonstandard de-escalated treatments, which have subspecialty-specific nuances. A synthesis of the multidisciplinary deintensification data and current treatment standards is important for the oncology community to reinforce best practices and ensure optimal patient outcomes. In this review, the authors present a summary and comparison of prospective HPV-positive OPC de-escalation trials. Chemotherapy attenuation compromises outcomes without reducing toxicity. Limited data comparing transoral robotic surgery (TORS) with radiation raise concern over toxicity and outcomes with TORS. There are promising data to support de-escalating adjuvant therapy after TORS, but consensus on treatment indications is needed. Encouraging radiation deintensification strategies have been reported (upfront dose reduction and induction chemotherapy-based patient selection), but level I evidence is years away. Ultimately, stage and HPV status may be insufficient to guide de-escalation. The future of deintensification may lie in incorporating intratreatment response assessments to harness the powers of personalized medicine and integrate real-time surveillance.

Therapeutic strategies for systemic therapies of human papillomavirus-related oropharyngeal cancer.

Our understanding of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) and its molecular basis continues to evolve and produce important insights into customized therapeutic strategies. Novel therapeutics exploiting HPV-related targets are being evaluated in the incurable setting, while the favorable prognosis of locoregionally advanced disease has stimulated investigation into de-escalation strategies. There is much opportunity for better personalization of standard therapy according to HPV status. This review discusses both current and investigational therapeutic strategies for HPV-related OPC.

What if Acupuncture Were Covered by Insurance for Pain Management? A Cross-Sectional Study of Cancer Patients at One Academic Center and 11 Community Hospitals.

OBJECTIVE: In response to the national opioid crisis, governmental and medical organizations have called for broader insurance coverage of acupuncture to improve access to nonpharmacologic pain therapies, especially in cancer populations, where undertreatment of pain is prevalent. We evaluated whether cancer patients would be willing to use insurance-covered acupuncture for pain. DESIGN AND SETTING: We conducted a cross-sectional survey of cancer patients with pain at one academic center and 11 community hospitals. METHODS: We used logistic regression models to examine factors associated with willingness to use insurance-covered acupuncture for pain. RESULTS: Among 634 cancer patients, 304 (47.9%) reported willingness to use insurance-covered acupuncture for pain. In univariate analyses, patients were more likely to report willingness if they had severe pain (odds ratio [OR] = 1.59, 95% confidence interval [CI] = 1.03-2.45) but were less likely if they were nonwhite (OR = 0.59, 95% CI = 0.39-0.90) or had only received high school education or less (OR = 0.46, 95% CI = 0.32-0.65). After adjusting for attitudes and beliefs in multivariable analyses, willingness was no longer significantly associated with education (adjusted OR [aOR] = 0.78, 95% CI = 0.50-1.21) and was more negatively associated with nonwhite race (aOR = 0.49, 95% CI = 0.29-0.84). CONCLUSIONS: Approximately one in two cancer patients was willing to use insurance-covered acupuncture for pain. Willingness was influenced by patients' attitudes and beliefs, which are potentially modifiable through counseling and education. Further research on racial disparities is needed to close the gap in utilization as acupuncture is integrated into insurance plans in response to the opioid crisis.

MRI criteria for the diagnosis of pleomorphic adenoma: a validation study.

OBJECTIVES: To validate an MRI algorithm characteristic of pleomorphic adenoma (PA). STUDY DESIGN: Cross-sectional analysis. SETTING: Academic tertiary-care medical center. METHODS: A radiologic algorithm for the MRI diagnosis of PA was developed on the basis of five "high probability" criteria that all must be fulfilled for the MRI to qualify as a positive test result: bright T2-signal, sharp margins, heterogeneous nodular enhancement, lobulated contours, T2-dark rim. We then identified MRI images from our institutional database to test the diagnostic accuracy of the proposed algorithm. RESULTS: A total of 103 parotidectomy cases with adequate MRI studies were identified (pleomorphic adenoma n=41, mucoepidermoid carcinoma n=11, Warthin's tumor n=8, adenoid cystic carcinoma n=6, oncocytoma n=6, acinic cell carcinoma n=5, salivary duct carcinoma n=5, and other n=21). Eighteen of 21 cases that met all five "high probability" MRI criteria were consistent with PA on final histopathology; 3 were consistent with carcinoma. MRI had a specificity of 95.1% [95% confidence interval: 85.6-98.7%] and sensitivity of 43.9% [95% C.I.: 28.8-60.1%] for PA. The positive predictive value was 85.7% [95% C.I.: 70.4-100%] and the negative predictive value was 71.9% [95% C. I.: 62.0-81.9%]. The overall diagnostic accuracy was 74.8% [95% C.I.: 66.2-83.3%]. CONCLUSION: A "high probability" MRI is about 95% specific for pleomorphic adenoma. A subset of patients with MRI imaging that is highly suggestive of PA may reliably avoid further workup. The value of MRI in this setting is especially useful if preoperative fine needle aspiration is not readily available. A significant proportion of PAs, however, have indeterminate imaging features that overlap considerably with other benign and malignant lesions.

When Is Telemedicine Appropriate in the Management of Head and Neck Cancer? A Mixed-Methods Assessment Among Patients and Physicians.

PURPOSE: Evidence suggests that oncology patients are satisfied with and sometimes prefer telemedicine compared with in-person visits; however, data are scarce on when telemedicine is appropriate for specific cancer populations. In this study, we aim to identify factors that influence patient experience and appropriateness of telemedicine use among a head and neck cancer (HNC) population. METHODS: We performed a mixed-methods study at a multisite cancer center. First, we surveyed patients with HNC and analyzed factors that may influence their telemedicine experience using multivariate regression. We then conducted focus groups among HNC oncologists (n = 15) to evaluate their perception on appropriate use of telemedicine. RESULTS: From January to December 2020, we collected 1,071 completed surveys (response rate 24%), of which 551 first unique surveys were analyzed. About half of all patients (56%) reported telemedicine as "same or better" compared with in-person visits, whereas the other half (44%) reported "not as good or unsure." In multivariate analyses, patients with thyroid cancer were more likely to find telemedicine "same or better" (adjusted odds ratio, 2.08 [95% CI, 1.35 to 3.25]) compared with other HNC populations (mucosal/salivary HNC). Consistently, physician focus group noted that patients with thyroid cancer were particularly suited for telemedicine because of less emphasis on in-person examinations. Physicians also underscored factors that influence telemedicine use, including clinical suitability (treatment status, visit purpose, examination necessity), patient benefits (travel time, access), and barriers (technology, rapport-building). CONCLUSION: Patient experience with telemedicine is diverse among the HNC population. Notably, patients with thyroid cancer had overall better experience and were identified to be more appropriate for telemedicine compared with other patients with HNC. Future research that optimizes patient experience and selection is needed to ensure successful integration of telemedicine into routine oncology practice.

A phase 1 study of concurrent cabozantinib and cetuximab in recurrent or metastatic head and neck squamous cell cancer.

OBJECTIVES: Epidermal growth factor receptor (EGFR) inhibition with cetuximab is a standard treatment for head and neck squamous cell carcinoma (HNSCC). Activation of the receptor tyrosine kinases AXL, MET and VEGFR can mediate resistance to cetuximab. Cabozantinib, a multikinase inhibitor (MKI) targeting AXL/MET/VEGFR, has demonstrated antitumor activity in preclinical models of HNSCC. This investigator- initiated phase I trial evaluated the safety and efficacy of cetuximab plus cabozantinib in patients with recurrent/metastatic (R/M) HNSCC. MATERIALS AND METHODS: Patients received cetuximab concurrently with cabozantinib daily on a 28-day cycle. Using a 3 + 3 dose-escalation design, the primary endpoint was to determine the maximally tolerated dose (MTD) of cabozantinib. Secondary endpoints included overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) RESULTS: Among the 20 patients enrolled, most had prior disease progression on immune checkpoint inhibitors (95 %), platinum-based chemotherapy (95 %), and cetuximab (80 %). No dose-limiting toxicities were recorded and the MTD for cabozantinib was established to be 60 mg. Grade ≥ 3 adverse events occurred in 65 % of patients (n = 13). ORR was 20 %, with 4 partial responses (PRs). Two PRs were observed in cetuximab-naïve patients (n = 4), with an ORR of 50 % in this subgroup. In the overall population, DCR was 75 %, median PFS was 3.4 months and median OS was 8.1 months. CONCLUSION: Cetuximab plus cabozantinib demonstrated a manageable toxicity profile and preliminary efficacy in patients with heavily treated R/M HNSCC. The combination of cetuximab with MKIs targeting the AXL/MET/VEGFR axis warrants further investigation, including in cetuximab-naïve patients.

High-throughput injection with microfluidics using picoinjectors.

Adding reagents to drops is one of the most important functions in droplet-based microfluidic systems; however, a robust technique to accomplish this does not exist. Here, we introduce the picoinjector, a robust device to add controlled volumes of reagent using electro-microfluidics at kilohertz rates. It can also perform multiple injections for serial and combinatorial additions.

Assessment of Oncology Patient Engagement and Interest in Virtual Mind-Body Programming: Moving Toward Personalization of Virtual Care.

PURPOSE: Accelerated by the COVID-19 pandemic, the virtual platform has become a prominent medium to deliver mind-body therapies, but the extent to which patients engage in virtual mind-body programming remains unclear. This study aims to assess oncology patient engagement in a virtual mind-body program. METHODS: We surveyed oncology patients enrolled in a live-streamed (synchronous) virtual mind-body program in May 2021. Patients self-reported engagement by weekly attendance. We applied multivariate regression to identify associations of engagement with sociodemographic and clinical factors. As an exploratory analysis, we used machine learning to partition engagement subgroups to determine preferential interest in prerecorded (asynchronous) mind-body therapy videos. RESULTS: Among 148 patients surveyed (response rate: 21.4%), majority were female (94.5%), White (83.1%), age 65 years or older (64.9%), retired (64.2%), and in survivorship (61.8%). Patient engagement ranged from 1 to 13 classes/week (mean [standard deviation]: 4.23 [2.56]) and was higher for female (ß, .82; 95% CI, 0.01 to 1.62), non-White (ß, .63; 95% CI, 0.13 to 1.13), and retired patients (ß, .50; 95% CI, 0.12 to 0.88). The partition model identified three engagement subgroups: employed (low engagers), retired White (intermediate engagers), and retired non-White (high engagers). Particularly, low engagers had preferential interest in meditation videos (odds ratio, 2.85; 95% CI, 1.24 to 6.54), and both low and high engagers had preferential interest in Tai Chi videos (odds ratio, 2.26; 95% CI, 1.06 to 4.82). CONCLUSION: In this cross-sectional study among oncology patients, engagement in virtual mind-body programming was higher for female, non-White, and retired patients. Our findings suggest the need for both synchronous and asynchronous mind-body programming to meet the diverse needs of oncology patients.

Genetic manipulation of AML1-ETO-induced expansion of hematopoietic precursors in a Drosophila model.

Among mutations in human Runx1/AML1 transcription factors, the t(8;21)(q22;q22) genomic translocation that creates an AML1-ETO fusion protein is implicated in etiology of the acute myeloid leukemia. To identify genes and components associated with this oncogene we used Drosophila as a genetic model. Expression of AML1-ETO caused an expansion of hematopoietic precursors in Drosophila, which expressed high levels of reactive oxygen species (ROS). Mutations in functional domains of the fusion protein suppress the proliferative phenotype. In a genetic screen, we found that inactivation of EcRB1 or activation of Foxo and superoxide dismutase-2 (SOD2) suppress the AML1-ETO-induced phenotype by reducing ROS expression in the precursor cells. Our studies indicate that ROS is a signaling factor promoting maintenance of normal as well as the aberrant myeloid precursors and suggests the importance of antioxidant enzymes and their regulators as targets for further study in the context of leukemia.

Comparison of Objective Measures of Trismus and Salivation With Patient-Reported Outcomes Following Treatment for Head and Neck Cancer.

Importance: Xerostomia and reduced mouth opening are negatively associated with quality of life after radiation therapy (RT) for head and neck cancer. Studies comparing objective measures of function with patient-reported outcomes (PROs) have not revealed a clear association. Objective: To determine how much of the variation in PROs is explained by objective measures of salivary gland and oral cavity functions (salivary flow and maximal interincisal opening). Design, Setting, and Participants: This cross-sectional study at a single academic cancer center evaluated 112 patients who underwent RT for head and neck cancer between January 2016 and March 2021. Measurements of pre-RT and post-RT saliva and a complete PROs scale within 6 months of the post-RT measurement were analyzed using pairwise associations. Interventions: Three independently scored PRO scales from the validated FACE-Q Head and Neck Cancer Module were evaluated: eating and drinking, eating distress, and salivation. Three objective measures were analyzed: maximal interincisal opening, stimulated salivary flow, and unstimulated salivary flow. Main Outcomes and Measures: Univariable linear regression models were performed for each PRO against each objective measure, and coefficients of determination (R2) and 95% CIs were reported. Results: The patient cohort comprised 86 men (77%). Median age was 61 years (IQR, 53-68 years), 89 patients (80%) were White, and 61 patients (54%) were current or former smokers. Unstimulated saliva accounted for only a small portion of variation on the salivation scale (R2 = 14.0%). The remaining associations were even smaller (R2 = 5.0%-10.0%). No upper 95% CI bound included an R2 of 30%, suggesting that objective measurements do not explain a high level of the variation in PROs. Conclusions and Relevance: In this cross-sectional study, objective measurements of salivary flow and mouth opening explained only a small fraction of variation in PROs. These findings suggest that factors other than objective function, including patient adaptation, are the dominant influence on PROs in this population. Patient-reported outcomes should be integrated into head and neck cancer clinical care and research. Additional research is required to evaluate which clinicopathological factors influence PROs for salivation, eating and drinking, and eating distress.

A prospective study on the prevalence of hydronephrosis in women with pelvic organ prolapse and their outcomes after treatment.

INTRODUCTION AND HYPOTHESIS: This work aims to study the prevalence of hydronephrosis and its associated factors in women with pelvic organ prolapse (POP) and to assess the effect on hydronephrosis following treatment for POP. METHODS: In this prospective observational study, 233 patients with POP were staged by the Pelvic Organ Prolapse-Quantification system, followed by sonographic measurement of bilateral renal pelvis to identify presence of hydronephrosis. Follow-up scan for hydronephrosis was performed after patients were treated for the POP. RESULTS: The prevalence of hydronephrosis was 10.3% (95% confidence interval (CI), 6% and 14%). Although patient's age, higher parity, and the presence of diabetes mellitus and hypertension were more common in the group with hydronephrosis, logistic regression analysis indicated that only the severity of POP was an independent risk factor for hydronephrosis. The odds ratio in stages 3 to 4 POP for hydronephrosis was 3.4 (95% CI, 1.3 and 9.2). Hydronephrosis resolved in 95% of patients after they received treatment for POP. CONCLUSIONS: The prevalence of hydronephrosis was 10.3% in patients with POP and patients with stages 3 to 4 POP were at particular higher risk. Hydronephrosis resolved in most of the patients after treatment for the prolapse.

Acupuncture versus cognitive behavioral therapy for pain among cancer survivors with insomnia: an exploratory analysis of a randomized clinical trial.

Pain and insomnia often co-occur and impair the quality of life in cancer survivors. This study evaluated the effect of acupuncture versus cognitive behavioral therapy for insomnia (CBT-I) on pain severity among cancer survivors with comorbid pain and insomnia. Using data from the CHOICE trial that compared acupuncture versus CBT-I for insomnia among cancer survivors, we analyzed the effect of interventions on pain outcomes in 70 patients with moderate to severe baseline pain. Interventions were delivered over eight weeks. We assessed average pain severity (primary outcome) and pain interference at baseline, week 8, and week 20. We further defined insomnia and pain responders as patients who achieved clinically meaningful improvement in insomnia and pain outcomes, respectively, at week 8. We found that compared with baseline, the between-group difference (-1.0, 95% CI -1.8 to -0.2) was statistically significant favoring acupuncture for reduced pain severity at week 8 (-1.4, 95% CI -2.0 to -0.8) relative to CBT-I (-0.4, 95% CI-1.0 to 0.2). Responder analysis showed that 1) with acupuncture, insomnia responders reported significantly greater pain reduction from baseline to week 4, compared with insomnia non-responders (-1.5, 95% CI -2.7 to -0.3); 2) with CBT-I, pain responders reported significantly greater insomnia reduction at week 8, compared with pain non-responders (-4.7, 95% CI -8.7 to -1.0). These findings suggest that among cancer survivors with comorbid pain and insomnia, acupuncture led to rapid pain reductions, which contributed to a decrease in insomnia, whereas CBT-I had a delayed effect on pain, possibly achieved by insomnia improvement.

ChemoPalRx-A Mobile App That Enhances Chemotherapy Prescription Accuracy: A Cross-Sectional Study.

PURPOSE: ChemoPalRx is a novel provider order entry mobile application for chemotherapy. This study aims to evaluate the accuracy of prescribing chemotherapy using ChemoPalRx versus handwritten orders at a safety-net hospital in Los Angeles. METHODS: In a cross-sectional study from October 2019 to December 2019, we evaluated all outpatient chemotherapy orders for accuracy. Our primary predictor was type of prescription, dichotomized as handwritten or ChemoPalRx. Primary outcome was accuracy, dichotomized as accurate if no error was made on an order and as inaccurate if any error was made. Preplanned subgroup analyses were performed with covariates including provider experience, complexity of order, and day of order submission. We characterized error type and analyzed our data using univariate and multivariate logistic regression models. RESULTS: Among 288 orders (78.5% handwritten; 21.5% ChemoPalRx), prescription accuracy was higher among ChemoPalRx (93.5%) compared with handwritten orders (81.4%; P = .012). In multivariate analysis, prescription accuracy remained superior for ChemoPalRx after adjusting for provider experience, complexity of order, and day of order submission (adjusted odds ratio, 1.82; P = .012). Compared with handwritten orders, ChemoPalRx orders had less missing or incorrect information (1.6% v 13.7%; P = .0016). ChemoPalRx orders were also more accurate on prescriptions that contained two or fewer medications (92.2% v 80.2%; P = .032), submitted on the highest patient-volume clinic day of the week (96.7% v 83.2%; P = .035), and generated by a senior fellow or an attending (97.3% v 76.9%; P = .001). CONCLUSION: ChemoPalRx is associated with improved chemotherapy prescription accuracy over handwritten orders in the safety-net hospital setting and may serve as an alternative prescribing tool for oncology practices.

Understanding the Heterogeneity of Obesity and the Relationship to the Brain-Gut Axis.

Obesity is best understood as a multifactorial metabolic imbalances disorder. In a cross-sectional study, we aimed to explore sociodemographic and dietary determinants of obesity in relation to brain-gut homeostasis among overweight and obese individuals. Multivariate logistic regression models were used to examine obesity and its association with sociodemographic and dietary factors. Biological variables examined included the gut microbiome, fecal amino acid metabolites and brain structural volumes. Among 130 participants, there were higher odds of obesity if individuals were Hispanic (adjusted odds ratio (aOR) 1.56, p = 0.014). Compared to non-Hispanics, Hispanics differed in gut microbial composition (p = 0.046) with lower microbial species richness (Chao1) (p = 0.032) and evenness (Shannon) (p = 0.0029). Fourteen of the twenty fecal amino acids including branch-chain- and aromatic- amino acids were increased among Hispanics (q < 0.05). Brain structural volumes in reward regions were decreased in Hispanics (pallidum, q = 0.036; brainstem, q = 0.011). Correlation patterns suggest complex brain-gut interactions differ by Hispanic ethnicity. In conclusion, Hispanics expressed a unique brain-gut microbial signature, which was associated with obesity despite sociodemographic and dietary differences. Addressing ethnic disparities guided by biologic phenotypes may unlock novel understanding of obesity heterogeneity and treatment strategies.

Genomewide clonal analysis of lethal mutations in the Drosophila melanogaster eye: comparison of the X chromosome and autosomes.

Using a large consortium of undergraduate students in an organized program at the University of California, Los Angeles (UCLA), we have undertaken a functional genomic screen in the Drosophila eye. In addition to the educational value of discovery-based learning, this article presents the first comprehensive genomewide analysis of essential genes involved in eye development. The data reveal the surprising result that the X chromosome has almost twice the frequency of essential genes involved in eye development as that found on the autosomes.

Virtual Tumor Board to Foster Interinstitutional Head and Neck Cancer Subspecialty Care.

This cross-sectional study evaluates the concordance on treatment and diagnostic recommendations between clinicians at 2 collaborating health systems.

Maternal views and acceptance of antenatal HIV screening in a university teaching hospital in Hong Kong.

OBJECTIVE: To assess maternal acceptance, knowledge, attitude, perceived risks and barriers toward antenatal HIV screening. STUDY DESIGN: Prospective anonymous survey of 1,519 pregnant women recruited in a university teaching hospital RESULTS: Women demonstrated fairly good knowledge of and a positive attitude toward HIV screening. Condom usage was 61.4%, and 25.3% of women had at least 1 risk factor for HIV infection. Support for mandatory and universal screening was 31.4% and 48.8%, respectively. A total of 82.6% women agreed to HIV testing. The major reason for declining the test was that women considered themselves to be at low risk (84.3%). Women with risk factors tended to prefer more aggressive methods of antenatal testing (P < .001) and more readily accepted HIV screening (89.8% vs. 73.1%, P < .001). CONCLUSION: Given the high acceptance rate in our local population, universal offering but voluntary testing is the optimal mode of antenatal HIV screening in Hong Kong.

DNA sequence analysis with droplet-based microfluidics.

Droplet-based microfluidic techniques can form and process micrometer scale droplets at thousands per second. Each droplet can house an individual biochemical reaction, allowing millions of reactions to be performed in minutes with small amounts of total reagent. This versatile approach has been used for engineering enzymes, quantifying concentrations of DNA in solution, and screening protein crystallization conditions. Here, we use it to read the sequences of DNA molecules with a FRET-based assay. Using probes of different sequences, we interrogate a target DNA molecule for polymorphisms. With a larger probe set, additional polymorphisms can be interrogated as well as targets of arbitrary sequence.

Necrotizing Fasciitis Associated with Staphylococcus lugdunensis.

Necrotizing fasciitis is a life-threatening soft tissue infection that results in rapid local tissue destruction. Type 1 necrotizing fasciitis is characterized by polymicrobial, synergistic infections that are caused by non-Group A streptococci, aerobic and anaerobic organisms. Type 2 necrotizing fasciitis involves Group A Streptococcus (GAS) with or without a coexisting staphylococcal infection. Here we provide the first report of necrotizing fasciitis jointly associated with the microbes Group B Streptococcus and Staphylococcus lugdunensis. S. lugdunensis is a commensal human skin bacterium known to cause often painful and prolonged skin and soft tissue infections. To our knowledge, however, this is the first case of Staph. lugdunensis-associated necrotizing fasciitis to be reported in the literature.