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Though specific growth rate (SGR) has potential prognostic value for oropharyngeal squamous cell carcinoma (OPSCC), there is sparse literature defining these rates. Our aims were to establish the SGRs of primary tumors (PTs) and lymph nodes (LNs) in OPSCC and to correlate SGR with oncologic outcome. A pilot study was designed with a retrospective analysis examining 54 patients from the University of California, Davis with OPSCC (diagnosed 2012-2019). Radiation oncology software and pretreatment serial CT scans were used to measure PT and LN volumes to calculate SGR and doubling time (DT). The mean PT-SGR was 1.2 ± 2.2%/day and the mean LN-SGR was 1.6 ± 1.9%/day. There was no statistically significant difference between slow-growing and fast-growing cohorts in terms of age, gender, smoking status, tumor subsite, HPV status (as determined with p16 staining), initial volume, or overall stage. SGR had no impact on 2-year overall survival, disease-free survival, or disease-specific survival. We found the average daily growth rates for OPSCC to be 1.2%/day and 1.6%/day. Our findings suggest PT- and LN-SGR are independent factors, not heavily influenced by known biomarkers and patient characteristics, without a statistical impact on prognosis. This information has value in patient counseling regarding tumor growth and in providing patients worried about fast-growing tumors the appropriate reassurance.

ObjectivesHead and neck cancer surgeons frequently interact with dying patients with advanced disease and their families, but little is known about their bereavement practices after a patient's death. The aim of this study is to elucidate the frequency of common bereavement practices, cited barriers to bereavement, and predictive physician factors that lead to an increase in bereavement practices among head and neck cancer surgeons.MethodsA 20-item survey was sent to 827 active surgeons of the American Head and Neck Society. Approval was obtained and the survey was distributed through the American Head and Neck Society. Demographics, frequency of common bereavement practices, empathy, and barriers were assessed. Multiple linear regression was performed to determine physician factors associated with more frequent bereavement follow-up.ResultsThere were 156 respondents (18.9% response rate). Overall, surgeons were more likely to usually/always call (48.5%) or send a letter (42.4%) compared with other practices such as attending funerals (0%), offering family meetings (18.6%), or referring family members to counseling (7.7%). Many barriers were cited as being at least somewhat important: being unaware about a patient's death (67.3%) was the most cited, whereas 51.3% cited a lack of mentorship/training in this area. Scoring higher on empathy questions (P ≤ .001) was associated with more frequent surgeon bereavement follow-up with the family of deceased patients.ConclusionThere is substantial practice variation among surgeons suggesting a lack of consensus on their roles in bereavement follow-up. Having higher empathy was predictive of higher engagement.Level of evidenceNA Laryngoscope, 132:1971-1975, 2022.

BackgroundThis study evaluated whether fluorescence lifetime imaging (FLIm), coupled with standard diagnostic workups, could enhance primary lesion detection in patients with p16+ head and neck squamous cell carcinoma of the unknown primary (HNSCCUP).MethodsFLIm was integrated into transoral robotic surgery to acquire optical data on six HNSCCUP patients' oropharyngeal tissues. An additional 55-patient FLIm dataset, comprising conventional primary tumors, trained a machine learning classifier; the output predicted the presence and location of HNSCCUP for the six patients. Validation was performed using histopathology.ResultsAmong the six HNSCCUP patients, p16+ occult primary was surgically identified in three patients, whereas three patients ultimately had no identifiable primary site in the oropharynx. FLIm correctly detected HNSCCUP in all three patients (ROC-AUC: 0.90 ± 0.06), and correctly predicted benign oropharyngeal tissue for the remaining three patients. The mean sensitivity was 95% ± 3.5%, and specificity 89% ± 12.7%.ConclusionsFLIm may be a useful diagnostic adjunct for detecting HNSCCUP.

Objectives: Early detection and accurate diagnosis of lymph node metastasis (LNM) in head and neck cancer (HNC) are crucial for enhancing patient prognosis and survival rates. Current imaging methods have limitations, necessitating new evaluation of new diagnostic techniques. This study investigates the potential of combining pre-operative CT and intra-operative fluorescence lifetime imaging (FLIm) to enhance LNM prediction in HNC using primary tumor signatures. Methods: CT and FLIm data were collected from 46 HNC patients. A total of 42 FLIm features and 924 CT radiomic features were extracted from the primary tumor site and fused. A support vector machine (SVM) model with a radial basis function kernel was trained to predict LNM. Hyperparameter tuning was conducted using 10-fold nested cross-validation. Prediction performance was evaluated using balanced accuracy (bACC) and the area under the ROC curve (AUC). Results: The model, leveraging combined CT and FLIm features, demonstrated improved testing accuracy (bACC: 0.71, AUC: 0.79) over the CT-only (bACC: 0.58, AUC: 0.67) and FLIm-only (bACC: 0.61, AUC: 0.72) models. Feature selection identified that a subset of 10 FLIm and 10 CT features provided optimal predictive capability. Feature contribution analysis identified high-pass and low-pass wavelet-filtered CT images as well as Laguerre coefficients from FLIm as key predictors. Conclusions: Combining CT and FLIm of the primary tumor improves the prediction of HNC LNM compared to either modality alone. Significance: This study underscores the potential of combining pre-operative radiomics with intra-operative FLIm for more accurate LNM prediction in HNC, offering promise to enhance patient outcomes.

Background: Novel, non-invasive diagnostic biomarkers that facilitate early intervention in head and neck cancer are urgently needed. Polyamine metabolites have been observed to be elevated in numerous cancer types and correlated with poor prognosis. The aim of this study was to assess the concentration of polyamines in the saliva and urine from head and neck cancer (HNC) patients, compared to healthy controls. Methods: Targeted metabolomic analysis was performed on saliva and urine from 39 HNC patient samples and compared to 89 healthy controls using a quantitative, targeted liquid chromatography mass spectrometry approach. Results: The metabolites N1-acetylspermine (ASP), N8-acetylspermidine (ASD) and N1,N12-diacetylspermine (DAS) were detected at significantly different concentrations in the urine of HNC patients as compared to healthy controls. Only ASP was detected at elevated levels in HNC saliva as compared to healthy controls. Conclusion: These data suggest that assessment of polyamine-based metabolite biomarkers within the saliva and urine warrants further investigation as a potential diagnostic in HNC patients.

BackgroundCutaneous soft-tissue sarcoma (CSTS) of the head and neck are rare and are known to have aggressive clinical course. The current study utilizes a population-based registry in the U.S. to characterize these malignancies and explore disparities.MethodsNational Cancer Institute's (NCI) Surveillance, Epidemiology and End Result (SEER) database from 2000 to 2018 was queried to report incidence and survival data in 4253 cases in the U.S.ResultsMales were 5.37 times more likely and Non-Hispanic-White people (NHW) were 4.62 times more likely than females and Non-Hispanic-Black people (NHB) to develop CSTS of the head and neck. The overall incidence was 0.27 per 100,000 persons in 2018, with a significant increase since 2000. Advanced age and stage, histologic group other than 'fibromatous sarcoma' and lower SES groups were independent factors for worse overall survival.ConclusionsCSTS of the head and neck demonstrate sex and racial/ethnic disparities in incidence and socioeconomic disparities in overall survival.Level of evidenceII.

ObjectivesTo describe the impact that the coronavirus disease 2019 (COVID-19) pandemic had on the presentation of patients with head and neck cancer in a single tertiary care center.Study designRetrospective cohort study.SettingAcademic institution.MethodsWe performed a retrospective review of patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC) who presented as new patients between September 10, 2019, and September 11, 2020. Patients presenting during the 6 months leading up to the announcement of the pandemic (pre-COVID-19 period) on March 11, 2020, were compared to those presenting during the first 6 months of the pandemic (COVID-19 period). Demographics, time to diagnosis and treatment, and tumor characteristics were analyzed.ResultsThere were a total of 137 patients analyzed with newly diagnosed malignancies. There were 22% fewer patients evaluated during the COVID-19 timeframe. The groups were similar in demographics, duration of symptoms, time to diagnosis, time to surgery, extent of surgery, and adjuvant therapy. There was a larger proportion of tumors classified as T3/T4 (61.7%) in the COVID-19 period vs the pre-COVID-19 period (40.3%) (P = .024), as well as a larger median tumor size during the COVID-19 period (P = .0002). There were no differences between nodal disease burden (P = .48) and distant metastases (P = .42).ConclusionDespite similar characteristics, time to diagnosis, and surgery, our findings suggest that there was an increase in primary tumor burden in patients with HNSCC during the early COVID-19 pandemic.

Inactive state-selective KRAS(G12C) inhibitors.sup.1-8 demonstrate a 30-40% response rate and result in approximately 6-month median progression-free survival in patients with lung cancer.sup.9. The genetic basis for resistance to these first-in-class mutant GTPase inhibitors remains under investigation. Here we evaluated matched pre-treatment and post-treatment specimens from 43 patients treated with the KRAS(G12C) inhibitor sotorasib. Multiple treatment-emergent alterations were observed across 27 patients, including alterations in KRAS, NRAS, BRAF, EGFR, FGFR2, MYC and other genes. In preclinical patient-derived xenograft and cell line models, resistance to KRAS(G12C) inhibition was associated with low allele frequency hotspot mutations in KRAS(G12V or G13D), NRAS(Q61K or G13R), MRAS(Q71R) and/or BRAF(G596R), mirroring observations in patients. Single-cell sequencing in an isogenic lineage identified secondary RAS and/or BRAF mutations in the same cells as KRAS(G12C), where they bypassed inhibition without affecting target inactivation. Genetic or pharmacological targeting of ERK signalling intermediates enhanced the antiproliferative effect of G12C inhibitor treatment in models with acquired RAS or BRAF mutations. Our study thus suggests a heterogenous pattern of resistance with multiple subclonal events emerging during G12C inhibitor treatment. A subset of patients in our cohort acquired oncogenic KRAS, NRAS or BRAF mutations, and resistance in this setting may be delayed by co-targeting of ERK signalling intermediates. These findings merit broader evaluation in prospective clinical trials. Multiple treatment-emergent alterations appear in patients with advanced-stage cancer who were treated with a KRAS inhibitor., Author(s): Yulei Zhao [sup.1] , Yonina R. Murciano-Goroff [sup.2] , Jenny Y. Xue [sup.1] [sup.3] , Agnes Ang [sup.4] , Jessica Lucas [sup.1] , Trang T. Mai [sup.1] , Arnaud [...]

Though specific growth rate (SGR) has potential prognostic value for oropharyngeal squamous cell carcinoma (OPSCC), there is sparse literature defining these rates. Our aims were to establish the SGRs of primary tumors (PTs) and lymph nodes (LNs) in OPSCC and to correlate SGR with oncologic outcome. A pilot study was designed with a retrospective analysis examining 54 patients from the University of California, Davis with OPSCC (diagnosed 2012–2019). Radiation oncology software and pretreatment serial CT scans were used to measure PT and LN volumes to calculate SGR and doubling time (DT). The mean PT-SGR was 1.2 ± 2.2%/day and the mean LN-SGR was 1.6 ± 1.9%/day. There was no statistically significant difference between slow-growing and fast-growing cohorts in terms of age, gender, smoking status, tumor subsite, HPV status (as determined with p16 staining), initial volume, or overall stage. SGR had no impact on 2-year overall survival, disease-free survival, or disease-specific survival. We found the average daily growth rates for OPSCC to be 1.2%/day and 1.6%/day. Our findings suggest PT- and LN-SGR are independent factors, not heavily influenced by known biomarkers and patient characteristics, without a statistical impact on prognosis. This information has value in patient counseling regarding tumor growth and in providing patients worried about fast-growing tumors the appropriate reassurance.

Objectives To describe the impact that the coronavirus disease 2019 (COVID-19) pandemic had on the presentation of patients with head and neck cancer in a single tertiary care center. Study Design Retrospective cohort study. Setting Academic institution. Methods We performed a retrospective review of patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC) who presented as new patients between September 10, 2019, and September 11, 2020. Patients presenting during the 6 months leading up to the announcement of the pandemic (pre–COVID-19 period) on March 11, 2020, were compared to those presenting during the first 6 months of the pandemic (COVID-19 period). Demographics, time to diagnosis and treatment, and tumor characteristics were analyzed. Results There were a total of 137 patients analyzed with newly diagnosed malignancies. There were 22% fewer patients evaluated during the COVID-19 timeframe. The groups were similar in demographics, duration of symptoms, time to diagnosis, time to surgery, extent of surgery, and adjuvant therapy. There was a larger proportion of tumors classified as T3/T4 (61.7%) in the COVID-19 period vs the pre–COVID-19 period (40.3%) ( P = .024), as well as a larger median tumor size during the COVID-19 period ( P = .0002). There were no differences between nodal disease burden ( P = .48) and distant metastases ( P = .42). Conclusion Despite similar characteristics, time to diagnosis, and surgery, our findings suggest that there was an increase in primary tumor burden in patients with HNSCC during the early COVID-19 pandemic.

Background: Cutaneous soft-tissue sarcoma (CSTS) of the head and neck are rare and are known to have aggressive clinical course. The current study utilizes a population-based registry in the U.S. to characterize these malignancies and explore disparities. Methods: National Cancer Institute’s (NCI) Surveillance, Epidemiology and End Result (SEER) database from 2000 to 2018 was queried to report incidence and survival data in 4253 cases in the U.S. Results: Males were 5.37 times more likely and Non-Hispanic-White people (NHW) were 4.62 times more likely than females and Non-Hispanic-Black people (NHB) to develop CSTS of the head and neck. The overall incidence was 0.27 per 100,000 persons in 2018, with a significant increase since 2000. Advanced age and stage, histologic group other than ‘fibromatous sarcoma’ and lower SES groups were independent factors for worse overall survival. Conclusions: CSTS of the head and neck demonstrate sex and racial/ethnic disparities in incidence and socioeconomic disparities in overall survival. Level of evidence: II.

Background: For patients with oral cavity squamous cell carcinoma (OCSCC) without evidence of nodal metastasis (cN0) on pre-operative evaluation, there are no clear guidelines who should undergo elective neck dissection (END) versus clinical surveillance. Objective: To identify CT imaging characteristics of sub-centimeter lymph nodes that would help predict the likelihood of nodal metastases on pathology. Methods: Retrospective review of cN0 OCSCC patients at a tertiary academic medical center was performed. Inclusion criteria included elective neck dissection, pre-operative CT imaging and presence of metastatic disease within lymph nodes. Control group consisted of patients without nodal metastases on pathology. CT features that were evaluated included asymmetric size, disrupted fatty hilum, asymmetric number, presence of cortical nodule, cortical nodule size, and round/oval shape. We evaluated the associations between CT LN features and the presence of metastases using multi-level mixed-effects logistic regression models. Model evaluation was performed using 5-fold cross-validation. The positive predictive value (PPV) and negative predictive value (NPV) were calculated. Results: 26 patients in each study and control groups were included. Three-level mixed-effects logistic regression models indicated round/oval shape (OR = 1.39, p =.01), asymmetric number (OR = 7.20, p =.005), and disrupted fatty hilum (OR = 3.31, p =.04) to be independently predictive in a 3-variable model with sensitivity = 38.0%, specificity = 92.0%, and PPV = 93.8%. Conclusions: In cN0 OCSCC patients undergoing END, round/oval shape, asymmetric number, and disrupted fatty hilum of lymph nodes on pre-operative CT imaging are novel and highly predictive of occult nodal disease. [ABSTRACT FROM AUTHOR]

Background: Novel, non-invasive diagnostic biomarkers that facilitate early intervention in head and neck cancer are urgently needed. Polyamine metabolites have been observed to be elevated in numerous cancer types and correlated with poor prognosis. The aim of this study was to assess the concentration of polyamines in the saliva and urine from head and neck cancer (HNC) patients, compared to healthy controls. Methods: Targeted metabolomic analysis was performed on saliva and urine from 39 HNC patient samples and compared to 89 healthy controls using a quantitative, targeted liquid chromatography mass spectrometry approach. Results: The metabolites N1-acetylspermine (ASP), N8-acetylspermidine (ASD) and N1,N12-diacetylspermine (DAS) were detected at significantly different concentrations in the urine of HNC patients as compared to healthy controls. Only ASP was detected at elevated levels in HNC saliva as compared to healthy controls. Conclusion: These data suggest that assessment of polyamine-based metabolite biomarkers within the saliva and urine warrants further investigation as a potential diagnostic in HNC patients.

Objective: To identify patient factors in older patients associated with making posttreatment visits in the first year after major head and neck oncologic surgery. Study Design: Retrospective cohort study. Setting: Academic institution. Methods: Patients aged ≥60 years who underwent a neck dissection with or without a free flap reconstruction were retrospectively analyzed. Data collected included patient demographics, comorbidities, social variables, perioperative course, and clinical visits. Results: Within a 1‐year postoperative period, the 181 patients in our cohort had a mean ± SD 6.37 ± 3.6 postoperative clinic visits; 70% attended at least 4 visits. Multivariable regression analysis showed a significant association with distance closer to the hospital (P =.013): for every 10‐mile increase in distance, the number of visits decreased by 0.15 (SE = 0.06). Additionally, receiving adjuvant radiation therapy (P =.0096) demonstrated significant associations: when compared with no adjuvant therapy, radiation therapy had on average 1.5 (SE = 0.56) more visits, and chemoradiation had 0.04 (SE = 0.73) more visits. Conclusion: Older patients who undergo major head and neck oncology surgery are more likely to attend posttreatment visits in the 1 year following surgery if they are discharged home rather than to a skilled nursing facility, live closer to the hospital, and undergo adjuvant radiation therapy. [ABSTRACT FROM AUTHOR]