Faculty Bibliography

IMPORTANCE/UNASSIGNED:Stage I squamous cell carcinoma (SCC) of the glottic larynx carries a favorable prognosis after treatment with endoscopic surgery or radiation therapy (RT). In addition to tumor control, goals of therapy include preservation of voice quality, swallow function, and breathing. Multidisciplinary consensus guidelines are needed to assist clinicians in treatment selection and the appropriate use of both surgical and radiation-based techniques. OBSERVATIONS/UNASSIGNED:Treatment of clinical T1N0 glottic SCC has evolved over time, with advances in both transoral laser microsurgery and RT designed to become more targeted and reduce the overall treatment burden for patients. When selecting a treatment option, consideration should be given to patient-specific factors, including tumor position/extent, age, and medical and psychosocial factors. This 16-member multidisciplinary American Radium Society (ARS) Head and Neck Cancer Appropriate Use Criteria (AUC) expert panel performed a review of the English-language medical literature from 2000 to 2022 to inform consensus guidelines. Clinical case variants were developed to represent commonly encountered clinical scenarios, and the RAND/UCLA appropriateness method was used to rate the appropriate use of various treatments. The modified Delphi method was used to reach consensus recommendations, which were approved by the ARS Executive Committee and subject to public comment per established ARS procedures. CONCLUSIONS AND RELEVANCE/UNASSIGNED:Given the range of treatment options available, early glottic SCC management should be done in a multidisciplinary fashion including otolaryngologists and radiation oncologists. The ARS Head and Neck AUC expert panel created an appropriate-use consensus document by performing a literature review of the current treatment strategies for stage I glottic SCC, providing recommendations regarding the appropriateness of surgery or RT for various clinical scenarios and highlighting areas of controversy and uncertainty.

Tumors of the paranasal sinus and nasal cavity (PNS/NC) are rare and exhibit diverse histology, anatomic subsite, and malignant potential. Early-stage disease is typically managed with surgery, and locally advanced disease is treated with a combination of surgery, radiotherapy, and chemotherapy. Clinical decision-making is commonly guided by limited retrospective evidence. To address this limitation, we performed a systematic review to inform evidence-based consensus for the management of common clinical scenarios, including the potential roles of radiation and systemic therapy to promote structural preservation, elective neck management, and radiation technique considerations. A librarian-mediated literature search identified 39 studies of adult patients with PNS/NC tumors treated with curative intent that met the study inclusion criteria. Search results were reported using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) methodology. A modified-Delphi process was used to guide consensus for the appropriate use of various management strategies. Strong consensus existed for the appropriateness of primary surgery for early-stage disease, approaches to locally advanced disease with minimal periorbital fat invasion, and the use of induction chemotherapy with response-directed local therapy. Consensus regarding nodal treatment and the use of proton therapy in the adjuvant setting was less robust. The rarity and diversity of PNS/NC tumors limit randomized phase III trials to guide management. As such, this systematic review and appropriate-use consensus statements provide clinical guidance for the management of this challenging disease spectrum.

The pancreas tumor microbiota may influence tumor microenvironment and influence survival in early-stage pancreatic ductal adenocarcinoma (PDAC); however, current studies are limited and small. We investigated the relationship of tumor microbiota to survival in 201 surgically resected patients with localized PDAC (Stages I-II), from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) cohorts. We characterized the tumor microbiome using RNA-sequencing data. We examined the association of the tumor microbiome with overall survival (OS), via meta-analysis with the Cox PH model. A microbial risk score (MRS) was calculated from the OS-associated microbiota. We further explored whether the OS-associated microbiota is related to host tumor immune infiltration. PDAC tumor microbiome α- and β-diversities were not associated with OS; however, 11 bacterial species, including species of Gammaproteobacteria, confirmed by extensive resampling, were significantly associated with OS (all Q < 0.05). The MRS summarizing these bacteria was related to a threefold change in OS (hazard ratio = 2.96 per standard deviation change in the MRS, 95% confidence interval = 2.26-3.86). This result was consistent across the two cohorts and in stratified analyses by adjuvant therapy (chemotherapy/radiation). Identified microbiota and the MRS also exhibited association with memory B cells and naïve CD4⁺ T cells, which may be related to the immune landscape through BCR and TCR signaling pathways. Our study shows that a unique tumor microbiome structure, potentially affecting the tumor immune microenvironment, is associated with poorer survival in resected early-stage PDAC. These findings suggest that microbial mechanisms may be involved in PDAC survival, potentially informing PDAC prognosis and guiding personalized treatment strategies.IMPORTANCEMuch of the available data on the PDAC tumor microbiome and survival are derived from relatively small and heterogeneous studies, including those involving patients with advanced stages of pancreatic cancer. There is a critical knowledge gap in terms of the tumor microbiome and survival in early-stage patients treated by surgical resection; we expect that advancements in survival may initially be best achieved in these patients who are treated with curative intent.

PURPOSE/OBJECTIVE:A digital visual communication tool was recently developed by MyCareGorithm which incorporates explanations of treatments and procedures for cancer patients. This study will evaluate if this novel tool can enhance both patient and provider satisfaction. METHODS:In an IRB approved, prospective, pilot study, patients and caregivers at a single institution receiving head and neck cancer radiation underwent an initial consult using this digital tool and completed a survey of 6 questions to evaluate their understanding of their disease. Providers completed a 7-question survey to rate their satisfaction. Patients and caregivers with 4 or more "Yes" answers and providers with 5 or more "Yes" answers were defined as "Satisfied". In order to obtain 90% power to detect that the proportion of "Satisfied" patients (assumed 75%) is greater than 50% with a significance level 5% using a one-sided Z test, we planned to enroll 30 patients. RESULTS:Thirty patients enrolled and completed all surveys. Most patients were male (66%), white (60%) and spoke English as a primary language (93%). Patients most commonly had oropharyngeal cancer (23%). Overall, 27 out of 30 of patients (90%; one sided 95%CI: 76.1%) were satisfied (z = 4.38, p < 0.05), 16 of the 17 caregivers (94%; one sided 95% CI: 74.8%) were satisfied and 100% of providers were satisfied with the digital tool. Most patients (90%) and caregivers (94%) felt that the tool improved their understanding of the disease. One male answered "No" for all 6 questions commenting that it was only marginally helpful. One female also answered "No" for all questions commenting that she did not find it helpful on its own without the provider explanation. Out of the 30 patients, 26 (87%) stayed at our institution to receive treatment. CONCLUSIONS:These findings showed high rates of patient, caregiver and provider satisfaction with their initial consult when incorporating a digital visual tool. Its routine use in clinical practice should be strongly considered.

BACKGROUND:Management of patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC) when cisplatin is contraindicated is controversial. We aimed to assess whether radiotherapy with concurrent and adjuvant durvalumab would improve outcomes compared with radiotherapy with cetuximab. METHODS:weekly beginning week 1 of radiotherapy (eight cycles), with intensity-modulated radiotherapy (70 Gy in 35 fractions over 7 weeks). Stratification factors were tumour and nodal stage, ECOG performance status and comorbidity, and primary site and p16 status. The phase 2 primary endpoint was progression-free survival in the intention-to-treat population. There was one prespecified interim futility analysis at 50% of progression-free survival information. If the observed hazard ratio was 1·0 or more, favouring cetuximab, early stopping would be considered. Extended follow-up analysis was post hoc. This trial is registered with ClinicalTrials.gov, NCT03258554, and is closed to enrolment. FINDINGS/RESULTS:Following a ten-patient safety lead-in, the phase 2 trial enrolled 190 patients from March 12, 2019, to July 30, 2021, 186 of whom were randomly assigned (123 to durvalumab and 63 to cetuximab). Median age was 72 years (IQR 64-77), 30 (16%) patients were women and 156 (84%) were men. Phase 2 accrual was suspended in July 30, 2021, following an interim futility analysis, and permanently closed in Sept 1, 2022. The phase 3 part of the trial was not conducted. At a median follow-up of 2·3 years (IQR 1·9-3·1) for the extended follow-up (data cutoff July 31, 2023; post-hoc analysis), 2-year progression-free survival was 50·6% (95% CI 41·5-59·8) in the durvalumab group versus 63·7% (51·3-76·1) in the cetuximab group (hazard ratio 1·33 [95% CI 0·84-2·12]; p=0·89). Adverse events were similar in both groups. The most common grade 3-4 adverse events were dysphagia (26 [22%] of 119 patients in the durvalumab group vs 18 [30%] of 61 patients in the cetuximab group), lymphopenia (33 [28%] vs 20 [33%]), and oral mucositis (13 [11%] vs 11 [18%]). Four (3%) patients in the durvalumab group and one (2%) in the cetuximab group died from treatment-related adverse events (death not otherwise specified, laryngeal oedema, lung infection, and respiratory failure in the durvalumab group and sudden death not otherwise specified in the cetuximab group). INTERPRETATION/CONCLUSIONS:Our findings suggest that durvalumab did not improve outcomes compared with cetuximab in patients with HNSCC with contraindications to cisplatin. Further trials are needed to define the standard of care for this population. FUNDING/BACKGROUND:US National Cancer Institute and AstraZeneca.

Surveillance for survivors of head and neck cancer (HNC) is focused on early detection of recurrent or second primary malignancies. After initial restaging confirms disease-free status, the use of surveillance imaging for asymptomatic patients with HNC is controversial. Our objective was to comprehensively review literature pertaining to imaging and biomarker surveillance of asymptomatic patients treated for head and neck squamous cell carcinoma and to convene a multidisciplinary expert panel to provide appropriate use criteria for surveillance in representative clinical scenarios. The evidence base for the appropriate use criteria was gathered through a librarian-mediated search of literature published from 1990 to 2022 focused on surveillance imaging and circulating tumor-specific DNA for nonmetastatic head and neck squamous cell carcinoma using MEDLINE (Ovid), Embase, Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials. The systematic review was reported according to PRISMA guidelines. Using the modified Delphi process, the expert panel voted on appropriate use criteria, providing recommendations for appropriate use of surveillance imaging and human papillomavirus (HPV) circulating tumor DNA. Of 5178 studies identified, 80 met inclusion criteria (5 meta-analyses/systematic reviews, 1 randomized control trial, 1 post hoc analysis, 25 prospective, and 48 retrospective cohort studies [with ≥50 patients]), reporting on 27,525 patients. No large, randomized, prospective trials examined whether asymptomatic patients who receive surveillance imaging or HPV circulating tumor DNA monitoring benefit from earlier detection of recurrence or second primary tumors in terms of disease-specific or quality-of-life outcomes. In the absence of prospective data, surveillance imaging for HNC survivors should rely on individualized recurrence-risk assessment accounting for initial disease staging, HPV disease status, and tobacco use history. There is an emerging surveillance role for circulating tumor biomarkers.

BACKGROUND/UNASSIGNED:Patients with head and neck cancer (HNC) often experience high symptom burden leading to lower quality of life (QoL). OBJECTIVE/UNASSIGNED:This study aims to conceptually model optimal cutpoint by examining where total number of patient-reported symptoms exceeds patients' coping capacity, leading to a decline in QoL in patients with HNC. METHODS/UNASSIGNED:Secondary data analysis of 105 individuals with HNC enrolled in a clinical usefulness study of the NYU Electronic Patient Visit Assessment (ePVA)©, a digital patient-reported symptom measure. Patients completed ePVA and European Organization for Research and Treatment of Cancer (EORTC©) QLQ-C30 v3.0. The total number of patient-reported symptoms was the sum of symptoms as identified by the ePVA questionnaire. Analysis of variance (ANOVA) was used to define optimal cutpoint. RESULTS/UNASSIGNED:<.0001). CONCLUSIONS/UNASSIGNED:In HNC, defining optimal cutpoints in the total number of patient-reported symptoms is feasible. IMPLICATIONS FOR PRACTICE/UNASSIGNED:Cutpoints in the total number of patient-reported symptoms may identify patients experiencing a high symptom burden from HNC. FOUNDATIONAL/UNASSIGNED:Using optimal cutpoints of the total number of patient-reported symptoms may help effectively align clinical resources with patients' symptom burden.

OBJECTIVES/OBJECTIVE:Lacrimal gland cancer is a rare malignancy with little data known about its pathologic characteristics or optimal management. We performed a large database analysis using the National Cancer Database (NCDB) to elucidate this unusual condition. METHODS:Patients with lacrimal gland cancer diagnosed between 2004 and 2018 were included in the analysis. Using available clinical data, we excluded all patients with histologies likely reflective of lacrimal sac or duct cancer, which are coded similarly to lacrimal gland cancer in the NCDB. Kaplan-Meier analysis was used to estimate overall survival (OS), and Cox proportional hazards models were used to indicate covariates associated with survival. RESULTS:A total of 440 cases of lacrimal gland cancer were included in the analysis, with a median follow-up of 52.9 months. The five-year OS for the entire cohort was 65.0%. Adenoid cystic carcinoma was the predominant histology (47.3%). Cox models showed that improved OS was associated with surgical resection (UVA: p < 0.001; MVA: p = 0.035). A detriment in OS was associated with increasing age, Charlson-Deyo score of 1, T4 stage, and positive margins and on UVA for adenocarcinoma and malignant mixed tumor histology. CONCLUSION/CONCLUSIONS:Adenoid cystic carcinoma comprises the plurality of lacrimal gland cancers. About half of patients with lacrimal gland carcinoma will live beyond 10 years, underscoring the importance of reduced morbidity of treatment. Surgical management is associated with improved prognosis. Further study will elucidate the role of surgical excision and radiotherapy in lacrimal gland cancer.