Neighborhood-Level Disadvantage and Delayed Adjuvant Therapy in Head and Neck Cancer.

Importance: For patients with head and neck squamous cell carcinoma (HNSCC), initiation of postoperative radiation therapy (PORT) within 6 weeks of surgery is recommended by the National Comprehensive Cancer Network Guidelines and the Commission on Cancer. Although individual-level measures of socioeconomic status are associated with receipt of timely, guideline-adherent PORT, the role of neighborhood-level disadvantage has not been examined. Objective: To characterize the association of neighborhood-level disadvantage with delays in receiving PORT. Design, Setting, and Participants: This retrospective cohort study included 681 adult patients with HNSCC undergoing curative-intent surgery and PORT from 2018 to 2020 at 4 US academic medical centers. The data were analyzed between June 21, 2023, and March 5, 2024. Main Outcome Measures and Measures: The primary outcome was delay in initiating guideline-adherent PORT (ie, >6 weeks after surgery). Time-to-PORT (TTP) was a secondary outcome. Census block-level Area Deprivation Index (ADI) scores were calculated and reported as national percentiles (0-100); higher scores indicate greater deprivation. The association of ADI scores with PORT delay was assessed using multivariable logistic regression adjusted for demographic, clinical, and institutional characteristics. PORT initiation across ADI score population quartiles was evaluated with cumulative incidence plots and Cox models. Results: Among 681 patients with HNSCC undergoing surgery and PORT (mean [SD] age, 61.5 [11.2] years; 487 [71.5%] men, 194 [29.5%] women) the PORT delay rate was 60.8% (414/681) and median (IQR) TTP was 46 (40-56) days. The median (IQR) ADI score was 62.0 (44.0-83.0). Each 25-point increase in ADI score was associated with a corresponding 32% increase in the adjusted odds ratio (aOR) of PORT delay (aOR, 1.32; 95% CI, 1.07-1.63) on multivariable regression adjusted for institution, age, race and ethnicity, insurance, comorbidity, cancer subsite, stage, postoperative complications, care fragmentation, travel distance, and rurality. Increasing ADI score population quartiles were associated with increasing TTP (hazard ratio of PORT initiation, 0.71; 95% CI, 0.53-0.96; 0.59; 95% CI, 0.44-0.77; and 0.54; 95% CI, 0.41-0.72; for ADI quartiles 2, 3, and 4 vs ADI quartile 1, respectively). Conclusions and Relevance: Increasing neighborhood-level disadvantage was independently associated with a greater likelihood of PORT delay and longer TTP in a dose-dependent manner. These findings indicate a critical need for the development of multilevel strategies to improve the equitable delivery of timely, guideline-adherent PORT.

Target Delineation in Postoperative Radiation Therapy for Head and Neck Cancer After Flap Reconstruction.

Delineation of the clinical target volume (CTV) after resection of head and neck cancer can be challenging, especially after flap reconstruction. The main area of contention is whether the entire flap should be included in the CTV. Several case series have reported marginal misses and intraflap failures when the entire flap was not routinely included in the CTV. On the other hand, available data have not convincingly demonstrated a detriment to long-term outcomes using intensity modulated radiotherapy after flap reconstruction. On the contrary, postoperative radiation can facilitate epilation and mucosalization of the flap tissue, reduce flap bulk, and improve long-term esthetic and functional outcomes. Therefore, our standard practice is to include the entire flap in the CTV. In certain scenarios, we may allow for a lower dose to part of flap distant from the resection bed than the flap-tumor bed junction, where recurrences are most likely. We provide three case vignettes describing such scenarios where sparing part of the flap, and more importantly, the nearby uninvolved native tissue, from high-dose radiation may be justified.

Diagnostic accuracy of FNA to determine HPV status in HPV-associated oropharyngeal squamous cell carcinoma.

PURPOSE/OBJECTIVE(S): Accurate diagnosis of human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC) affects prognosis and can alter the treatment plan. We evaluated the diagnostic accuracy of FNA biopsies to determine malignancy and HPV status in OPSCC at our institution. METHODS: Pathology samples from consecutive patients with pathologically confirmed HPV-associated OPSCC who underwent FNA of a cervical lymph node during initial diagnostic work-up were retrospectively analyzed between November 2015 and August 2021. RESULTS: Initial FNA was diagnostic for malignancy in 109/148 (73.6%) patients and non-diagnostic in 39/148 (26.4%). P16 staining of FNAs positive for malignancy showed: 54/109 (49.5%) p16 positive, 6/109 (5.5%) p16 negative, 49/109 (45.0%) p16 indeterminate. In patients with an initial non-diagnostic sampling or p16 indeterminate, repeat FNA was performed in 30/88 (34.1%) patients. Of the 30 repeat FNAs: 23/30 (76.7%) were diagnostic of malignancy and 7/30 (23.3%) remained non-diagnostic for malignancy. Of the 23 repeat FNAs diagnostic of malignancy: 16/23 (69.6%) were p16 positive and 7/23 (30.4%) were p16 indeterminate. In summary, 88/148 (59.5%) initial FNAs and 14/30 (46.7%) of repeat FNAs were non-diagnostic of malignancy or p16 indeterminate. Final yield of FNA biopsies (initial and first repeat FNA) to diagnose malignancy and p16 status was 70/148 (47.3%). CONCLUSIONS: Fine needle aspirations of lymph nodes in patients with HPV-associated OPSCC are frequently non-diagnostic for malignancy or indeterminate for p16 status, requiring repeat FNA or biopsy of the primary site. This can potentially cause treatment delay and increase morbidity and cost to the patient.

Consensus Quality Measures and Dose Constraints for Head and Neck Cancer with an emphasis on Oropharyngeal and Laryngeal Cancer from the Veterans Affairs Radiation Oncology Quality Surveillance Program and American Society for Radiation Oncology Expert Panel.

PURPOSE: Safeguarding high-quality care using evidence-based radiation therapy for patients with head and neck cancer is crucial to improving oncologic outcomes, including survival and quality of life. METHODS AND MATERIALS: The Veterans Administration (VA) National Radiation Oncology Program established the VA Radiation Oncology Quality Surveillance Program (VAROQS) to develop clinical quality measures (QM) in head and neck cancer. As part of the development of QM, the VA commissioned, along with the American Society for Radiation Oncology, a blue-ribbon panel comprising experts in head and neck cancer, to develop QM. RESULTS: We describe the methods used to develop QM and the final consensus QM, as well as aspirational and surveillance QM, which capture all aspects of the continuum of patient care from initial patient work-up, radiation treatment planning and delivery, and follow-up care, as well as dose volume constraints. CONCLUSION: These QM are intended for use as part of ongoing quality surveillance for veterans receiving radiation therapy throughout the VA as well as outside the VA. They may also be used by the non-VA community as a basic measure of quality care for head and neck cancer patients receiving radiation.

Engaging Physicians in Quality Improvement in a Hospital Setting: A Scoping Review.

Health care is at a critical moment. High rates of medical errors and decreasing quality of health care make it crucial that organizations focus on quality improvement (QI). For this work to be successful, it is essential to engage physicians, as they are key decision-makers, leaders, and influencers of care. Despite this fact, few organizations have successfully sustained physician engagement in QI. A scoping review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses model to understand barriers to and strategies for engaging physicians in QI. The most commonly cited strategies were: (1) having engaged and supportive senior leadership and (2) having data support for QI work. Additional strategies included: dedicated time, resources, and education for QI work; financial incentives; clarifying organizational goals; and developing pathways for promotion. A framework was then created to operationalize physician engagement in QI in the organization.

Assessment of Radiation Therapy Technologists' Workload and Situation Awareness: Monitoring 2 Versus 3 Collocated Display Monitors.

PURPOSE: This study aimed to assess the effect of monitoring 2 versus 3 collocated displays on radiation therapist technologists' (RTTs) workload (WL) and situation awareness (SA) during routine treatment delivery tasks. METHODS AND MATERIALS: Seven RTTs completed 4 simulated treatment delivery scenarios (2 scenarios per experimental condition; 2 vs 3 collocated displays) in a within-subject experiment. WL was subjectively measured using the National Aeronautics and Space Administration (NASA) Task Load Index, and objectively measured using eye activity measures. SA was subjectively measured using the SA rating technique, and objectively measured using the SA global assessment technique. Two-tailed paired t tests were conducted to test for differences in means when parametric assumptions were satisfied, otherwise Wilcoxon signed-rank tests were conducted. A .05 level of significance was applied to all statistical tests. RESULTS: No statistically and clinically significant differences were observed between monitoring 2 versus 3 monitors on eye tracking measures (blink rate: 9.4 [4.8] vs 9.6 [4.0]; task evoked pupillary response: 0.16 [0.14] vs 0.21 [0.15]; NASA Task Load Index: 34.7 [19.8] vs 35.3 [20.4]; SA rating technique: 19.3 [6.2] vs 19.5 [7.0]; and SA global assessment technique scores: 100 [0] vs 100 [0]). CONCLUSIONS: Our preliminary findings suggest that monitoring 3 collocated displays by 1 RTT does not impact WL and SA compared with monitoring 2 collocated displays. Only 2 of many possible configurations were investigated. If institutions removed the 3rd display based on the results of this study, there could be unforeseen error(s) if that display helped in situations not assessed in this study.

An evaluation of buparlisib for the treatment of head and neck squamous cell carcinoma.

INTRODUCTION: Five-year overall survival for head and neck squamous cell carcinoma (HNSCC) is relatively poor at around 50-66%, and there has been little improvement over the past several decades. PIK3CA alterations are common in HNSCC and offer a promising therapeutic target. AREAS COVERED: The authors discuss the PIK3 pathway and the use of PIK3 inhibitors in cancer, with a particular focus on HNSCC. A summary of the safety and efficacy of buparlisib, a class I pan-PI3K inhibitor, from several phase I and phase II HNSCC trials is provided. EXPERT OPINION: With a maximum tolerated dose of 100 mg/day and an acceptable toxicity profile, buparlisib may be effective in HNSCC, irrespective of PIK3CA mutational status. On-going clinical trials will help determine the developmental strategy of buparlisib while novel combinatory strategies including combination with immune checkpoint inhibitors should be considered. Importantly, biomarker strategies, including wider use of tumor sequencing and circulating tumor DNA, should be utilized to improve patient selection.

Practical Challenges of Mask-to-Mask Encounters with Patients with Head and Neck Cancers amid the Coronavirus Disease 2019 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has forced a re-design of care in radiation oncology. Perhaps more than any other disease site we commonly see, the evaluation and treatment of head and neck cancer has posed the greatest risk of COVID-19 transmission between patients and radiotherapy providers. In our early experience with the novel coronavirus, several staff members were exposed to a COVID-positive patient and this caused us to devise policies and procedures to mitigate further risk in a way that could practically be employed across a large health system while not compromising care delivery. Here, we formulate a concise summary of simple steps, including a novel thermoplastic mask fitting technique and procedures for intraoral immobilization devices, to guide practices and provide new layers of protection for both patients and staff.

Novel Strategies to Effectively De-escalate Curative-Intent Therapy for Patients With HPV-Associated Oropharyngeal Cancer: Current and Future Directions.

The treatment of patients with HPV-associated oropharyngeal cancer (HPV-OPC) is rapidly evolving and challenging the standard of care of definitive radiotherapy with concurrent cisplatin. There are numerous promising de-escalation strategies under investigation, including deintensified definitive chemoradiotherapy, transoral surgery followed by de-escalated adjuvant therapy, and induction chemotherapy followed by de-escalated locoregional therapy. Definitive radiotherapy alone or with cetuximab is not recommended for curative-intent treatment of patients with locally advanced HPV-OPC. The results of ongoing phase III studies are awaited to help answer key questions and address ongoing controversies to transform the treatment of patients with HPV-OPC. Strategies for de-escalation under investigation include the incorporation of immunotherapy and the use of novel biomarkers for patient selection for de-escalation.

Common error pathways seen in the RO-ILS data that demonstrate opportunities for improving treatment safety.

PURPOSE: The Radiation Oncology Incident Learning System (RO-ILS) receives event reports from facilities across the country. This effort extracted common error pathways seen in the data. These pathways, expressed as fault trees, demonstrate the need for, and opportunities for, preventing these errors and/or limiting their propagation to treatment. METHODS AND MATERIALS: As of the third quarter of 2016, 2344 event reports had been submitted to RO-ILS and reviewed. A total of 396 of the reports judged highest priority were rereviewed and assigned up to 3 keywords to classify events. Based on patterns among the keyword assignments, the data were further aggregated into pathways leading to 3 general error types: "problematic plan approved for treatment," "wrong shift instructions given to therapists," and "wrong shift performed at treatment." Fault trees were created showing how different errors at different stages in the treatment process combine to flow into these general error types. RESULTS: A total of 173 of the 396 (44%) events were characterized as belonging to 1 of these 3 general error types. Ninety-nine events were defined as "problematic plan approved for treatment," 40 as "wrong shift instructions given to therapists," and 34 as "wrong shift performed at treatment." Seventy-six of these events (44%) resulted in incorrectly delivered treatment. Event discovery was by therapists (n = 76), physicists (n = 45), physicians (n = 23), dosimetrists (n = 15), or not identified (n = 9); 5 events were found as a result of the patient questioning the staff. For the event type "problematic plan approved for treatment," 64 of the 99 (65%) events were attributable to physician error: incorrect target or dosing pattern prescribed. CONCLUSIONS: Data extracted from RO-ILS event reports demonstrate common error pathways in radiation oncology that propagate all the way to treatment. Additional study and coordination of efforts is needed to develop and share best practices to address the sources of these errors and curtail their propagation.

Integrating Palliative and Oncology Care for Patients with Advanced Cancer: A Quality Improvement Intervention.

BACKGROUND: Practice guidelines recommend palliative care for patients with advanced cancer, but gaps in access and quality of care persist. OBJECTIVE: To increase goals-of-care (GOC) communication for hospitalized patients with Stage IV cancer. METHODS: An interdisciplinary team designed a quality improvement intervention to enhance oncology palliative care, including training in communication skills and triggers for palliative care consults. SETTING/SUBJECTS: All adult inpatients with Stage IV cancer and unplanned admission at an 804-bed hospital affiliated with a National Cancer Institute (NCI) Comprehensive Cancer Center. MEASUREMENTS: The primary quality measure was the percentage of patients with Stage IV cancer who had a GOC discussion during hospitalization; secondary measures included screening for pain, dyspnea, spiritual needs, and outcomes of intensive care, hospice, and 30-day readmission. RESULTS: In the 11-month study period, n = 330, Stage IV cancer patients were hospitalized. Comparing the first three months with the final three months, rates of GOC discussion increased from 29% to 48% (p = 0.013), and specialty palliative care consultation increased from 18% to 33%, (p = 0.026). Rates of symptom screening, intensive care unit transfer, hospice, and 30-day re-admission did not change overall. However, patients with specialty palliative care more frequently had pain screening (91% vs. 81%, p = 0.020), spiritual assessment (48% vs. 10%, p < 0.001), and hospice referral (39% vs. 9%, p < 0.001), and they were less likely to be re-admitted within 30 days (12% vs. 21%, p = 0.059). DISCUSSION: Interdisciplinary quality improvement was effective to increase GOC discussions and palliative care consults for patients with Stage IV cancer.

The systematic application of quality measures and process control in clinical radiation oncology.

There has been growing emphasis on quality measures and process analysis techniques that may be implemented in the daily practice of radiation oncology to improve the overall quality of patient care. In this work, quality measures are a form of monitoring that should be actionable and specific to guide process improvement efforts. They are most effective when used to determine the level of execution proficiency against a standard. Control charts are an effective way to separate a change in the process from process noise such that the user can focus on issues that are more likely to improve quality. The field of radiotherapy would benefit from a common dashboard of quality measures for the different processes in radiation oncology clinics, and some suggestions are provided. The dashboard would be used to provide continuous feedback on a clinic's capability to maintain or exceed standards.

Immunofluorescent labeling of increased calpain expression and neuronal death in the spinal cord of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice.

Parkinson's disease (PD) is a movement disorder characterized by rigidity, tremor, and bradykinesia, originating from degeneration of dopaminergic neurons in the substantia nigra (SN), retrorubral area, and locus ceoruleus (LC). Calpain has been implicated in the pathophysiology of neurodegenerative diseases. Since the spinal cord (SC) and brain are integrally connected and calpain is involved in cell death and mitochondrial dysfunction, we hypothesized that SC neurons are also affected in PD. In order to examine this hypothesis, we examined both brain and SC from mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). To identify cells expressing calpain, double immunofluorescent labeling was performed with antibodies specific for calpain and a cell type (OX-42, GFAP, or NeuN). Combined terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and double immunofluorescent labeling were used to identify death of specific cells in the central nervous system (CNS). There was an increase in calpain expression in microglia, astrocytes, and neurons in the SC of MPTP-treated mice at 1 and 7 days, as compared to controls. TUNEL-positive neurons in the SC and SN showed apoptotic characteristics. These results demonstrated that neuronal death occurred not only in SN but also in the SC of MPTP-treated mice and has provided evidence for a possible calpain-mediated SC neuronal death in MPTP-induced parkinsonism in mice.

Calpain upregulation and neuron death in spinal cord of MPTP-induced parkinsonism in mice.

Parkinson's disease (PD) is a neurodegenerative disorder resulting in slowness, tremors, and imbalance. Treatment of mice with 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) is one of several models used to mimic PD in humans. Administration of MPTP leads to the production of 1-methyl-4-phenyl-2,3 dihydropyridinium (MPP(+)). MPP(+) is taken up by dopaminergic neurons, causing mitochondrial dysfunction and cell death. Because calpain is involved in neuronal cell death and mitochondrial dysfunction, we examined the level of calpain in neurons in the substantia nigra (SN) and hippocampus of MPTP-treated C57BL/6 mice. Because of the interconnections between spinal cord and upper central nervous system neurons, we examined morphology, calpain activity, and calpain expression in neurons by double immunofluorescence using calpain and neuron marker (NeuN) antibodies. In controls, calpain expression was low in SN, hippocampus, and spinal cord NeuN(+) cells, and the NeuN stain was concentrated around the nucleus. In mice sacrificed 24 h after administration of three 20 mg/kg doses of MPTP, calpain expression was slightly increased in SN and hippocampal neurons and moderately increased in spinal cord neurons. In these animals, the NeuN stain was less concentrated around the nuclear membrane. One week after MPTP treatment, calpain content in NeuN(+) cells was greatly increased in SN, hippocampus, and spinal cord. Morphologically, SN and spinal cord neurons, treated for one week, were necrotic with a granular cytoplasmic NeuN content. Also, MPTP treatment upregulated calpain activity and mRNA level in spinal cord. These data suggest that following MPTP treatment, calpain causes neuronal death in SN as well as in spinal cord.