L-LOP/LOPP for the treatment of canine gastrointestinal/hepatosplenic lymphoma.

Canine gastrointestinal (GI) and hepatosplenic (HS) high-grade (large cell) lymphomas are uncommon forms of canine lymphomas, with a very poor response to chemotherapy and a very poor prognosis. Currently, there are no established effective chemotherapy protocols for canine GI/HS lymphomas. This case series aimed to retrospectively evaluate the efficacy of lomustine-based protocols L-LOP (L-asparaginase, lomustine, vincristine, and prednisolone) and L-LOPP (with the addition of procarbazine) for treatment of canine GI/HS lymphomas. Medical records of dogs with cytologically or histologically diagnosed lymphoma at CityU Veterinary Medical Centre from 2019 to 2022 were retrospectively reviewed. The L-LOP/LOPP treatment protocol was well tolerated with rare severe adverse events. Median progression-free survival for GI and HS lymphoma was 56 days (range, 10-274 days) and 57 days (range 8-135 days) respectively; while median survival time for GI and HS lymphoma was 93 days (range 10-325 days) and 210 days (range 8-240 days) respectively.

68Ga-FAP-2286 PET of Solid Tumors: Biodistribution, Dosimetry, and Comparison with 18F-FDG.

Fibroblast activation protein (FAP), expressed in the tumor microenvironment of a variety of cancers, has become a target of novel PET tracers. The purpose of this report is to evaluate the imaging characteristics of 68Ga-FAP-2286, present the first-to our knowledge-dosimetry analysis to date, and compare the agent with 18F-FDG and FAPI compounds. Methods: Patients were administered 219 ± 43 MBq of 68Ga-FAP-2286 and scanned after 60 min. Uptake was measured in up to 5 lesions per patient and within the kidneys, spleen, liver, and mediastinum (blood pool). Absorbed doses were evaluated using MIM Encore and OLINDA/EXM version 1.1 using the International Commission on Radiological Protection publication 103 tissue weighting factor. Results: Forty-six patients were imaged with 68Ga-FAP-2286 PET. The highest average uptake was seen in sarcoma, cholangiocarcinoma, and colon cancer. The lowest uptake was found in lung cancer and testicular cancer. The average SUVmax was significantly higher on 68Ga-FAP-2286 PET than on 18F-FDG PET in cholangiocarcinoma (18.2 ± 6.4 vs. 9.1 ± 5.0, P = 0.007), breast cancer (11.1 ± 6.8 vs. 4.1 ± 2.2, P < 0.001), colon cancer (13.8 ± 2.2 vs. 7.6 ± 1.7, P = 0.001), hepatocellular carcinoma (9.3 ± 3.5 vs. 4.7 ± 1.3, P = 0.01), head and neck cancer (11.3 ± 3.5 vs. 7.6 ± 5.5, P = 0.04), and pancreatic adenocarcinoma (7.4 ± 1.8 vs. 3.7 ± 1.0, P = 0.01). The total-body effective dose was estimated at 1.16E-02 mSv/MBq, with the greatest absorbed organ dose in the urinary bladder wall (9.98E-02 mGy/MBq). Conclusion: 68Ga-FAP-2286 biodistribution, dosimetry, and tumor uptake were similar to those of previously reported FAPI compounds. Additionally,68Ga-FAP-2286 PET had consistently higher uptake than 18F-FDG PET. These results are especially promising in the setting of small-volume disease and differentiating tumor from inflammatory uptake.

The tumor microenvironment of benign and malignant salivary gland tumors.

BACKGROUND: Treatment of salivary gland tumors (SGTs) remains challenging. Little is known about the immune landscape of SGTs. We aimed to characterize the tumor microenvironment in benign and malignant SGTs. METHODS: Eleven benign and nine malignant tumors were collected from patients undergoing curative intent surgery. Specimens were analyzed using mass cytometry by time-of-flight. Immune cell populations were manually gated, and T cells were clustered using the FlowSOM algorithm. Population frequencies were compared between high-grade and low-grade malignancies, corrected for multiple hypothesis testing. RESULTS: There were trends towards increased CD4+ and CD8+ T cells among malignant tumors. High-grade malignancies exhibited trends towards higher frequencies of CD8+ PD-1+ CD39+ CD103+ exhausted T cells, CD4+ FoxP3+ TCF-1+ CD127- Tregs, and CD69+ CD25- CD4+ T cells compared to low-grade malignancies. CONCLUSION: SGTs exhibit significant immunologic diversity. High-grade malignancies tended to have greater infiltration of exhausted CD8+ T cells and Tregs, which may guide future studies for immunotherapy strategies.

Postoperative inpatient surgical complications following head and neck microvascular free tissue transfer.

BACKGROUND: Complications following head and neck microvascular free tissue transfer (MFTT) are common. Less is known about when they occur. METHOD: Retrospective study of patients with primary or recurrent head and neck cancer undergoing MFTT reconstruction at a tertiary care institution. MFTT reconstructions with inpatient postoperative complications were included. The Kruskal-Wallis test was used to compare median postoperative day (POD) onset of complication by flap type. RESULTS: Of 1090 patients undergoing MFTT reconstruction, 126 (11.6%) patients experienced inpatient complications including fibula (n = 35), anterolateral thigh (n = 60), or radial forearm (n = 31) MFTTs. POD onset was shortest for surgical site hematoma (median = 1 [IQR 1-5]), and longest for donor site infection (median = 11.5 [IQR 8-15]). There was no significant difference between flap types and POD onset of complications (p > 0.05). CONCLUSION: Hematoma formation and flap failure occur earliest during hospitalization, while dehiscence, infection, and fistula occur later. There is no difference in complication timing between flap types.

Rate of occult metastasis in lip squamous cell carcinoma: A systematic review and meta-analysis.

OBJECTIVES: The rate of occult metastasis in lip cancer is poorly studied. Management of the regional nodal basin in lip cancer is thus controversial. This study sought to understand the true rate of micrometastasis in lip cancer. MATERIALS AND METHODS: Systematic review and meta-analysis was conducted of English language studies reporting lip cancer sentinel node biopsy results. Studies were obtained from the PubMed database between the years 2000 and 2023 using the search terms "sentinel node biopsy" and "squamous cell carcinoma." Random effect and fixed effect meta-analyses were performed. RESULTS: Thirteen studies met inclusion criteria. Low heterogeneity was noted among the studies, as indicated by the I2 inconsistency test (I2 = 0%). The rate of occult metastasis ranged between 0 and 33% (mean 9%). A total of 189 lip sentinel node biopsies had been performed. Of these, 21 revealed occult nodal metastasis (11.1%, 95% CI 7.36%-16.44%). One step, generalized linear mixed modeling revealed the true rate of occult nodal metastasis to be 10% (95% CI (0.0504, 0.1746), p < 0.0001). CONCLUSION: The rate of occult metastasis in lip cancer approaches the threshold for elective management of the regional nodal basin. Sentinel node biopsy is optimally suited for management of high-risk early T stage lip cancer.

Prognostic risk factors of buccal squamous cell carcinoma: A case-control study.

OBJECTIVES: To describe the clinicopathologic presentation of buccal squamous cell carcinoma and identify risks factors for recurrence and overall survival. METHODS: This is a retrospective case-control study of patients with oral cavity squamous cell carcinoma (OCSCC) treated at a single tertiary care center between 2010 and 2022. All patients with buccal subsite OCSCC treated during this time frame were included and paired with a randomly selected age and gender matched patient with non-buccal OCSCC. Relevant data was collected via chart review. RESULTS: Seventy-seven patients with buccal SCC were matched with 77 non-buccal OCSCC controls. The median follow-up time was 27 months (IQR 14-61). Median age was 67 years (IQR 57-75) and 53% of the cohort was female. Twenty (26%) buccal SCC patients experienced a recurrence versus 19 (25%) in the controls. Age ≥65-years-old increased odds of all-cause mortality in the buccal SCC group, but not in the control group. Perineural invasion and positive margins increased odds of recurrence in the buccal group only. Overall survival and progression-free survival did not differ between the groups, despite a greater number of T2 buccal tumors and T1 non-buccal tumors. CONCLUSIONS: Buccal SCC presents at a higher T stage than other oral cavity SCC subsite and may exhibit variance in the pathologic risk factors that predict poor outcomes versus non-buccal OCSCC. Despite these relatively minor differences, however, oncologic outcomes between these groups were similar.

A supervised machine learning model for identifying predictive factors for recommending head and neck cancer surgery.

BACKGROUND: New patient referrals are often processed by practice coordinators with little-to-no medical background. Treatment delays due to incorrect referral processing, however, have detrimental consequences. Identifying variables that are associated with a higher likelihood of surgical oncological resection may improve patient referral processing and expedite the time to treatment. The study objective is to develop a supervised machine learning (ML) platform that identifies relevant variables associated with head and neck surgical resection. METHODS: A retrospective cohort study was conducted on 64 222 patient datapoints from the SEER database. RESULTS: The random forest ML model correctly classified patients who were offered head and neck surgery with an 81% accuracy rate. The sensitivity and specificity rates were 86% and 71%. The positive and negative predictive values were 85% and 73%. CONCLUSIONS: ML modeling accurately predicts head and neck cancer surgery recommendations based on patient and cancer information from a large population-based dataset. ML adjuncts for referral processing may decrease the time to treatment for patients with cancer.

Treatment Modality Impact on Patient-Reported Quality of Life in Human Papilloma Virus-Associated Oropharyngeal Carcinoma.

OBJECTIVE: To prospectively compare the impact of treatment modality on patient-reported quality of life (QOL) in human papillomavirus-associated oropharynx squamous cell carcinoma (HPV + OPSCC). STUDY DESIGN: Prospective cohort study. SETTING: Academic medical center. METHODS: One hundred one patients with American Joint Committee on Cancer (AJCC) 8th edition T1-3 N0-2 HPV + OPSCC completed the European Organization for Research and Treatment of Cancer Quality of Life Core questionnaire and Head and Neck Module pretreatment and 3-month and 1-year posttreatment. Mean score changes were compared to published minimal clinically important differences. RESULTS: Patients underwent surgery alone (SA: N = 42, 42%), surgery with adjuvant radiation (S-RT: N = 10, 10%), surgery with adjuvant chemoradiation (S-CRT: N = 8, 8%), definitive radiation (RT: N = 11, 11%), or definitive chemoradiation (CRT: N = 30, 30%). SA, S-[C]RT, and [C]RT patients all reported clinically significant difficulty with sense of taste/smell persisting at 1 year. S-[C]RT and [C]RT patients reported statistically and clinically significant worse salivary dysfunction and problems with social eating at 1 year than SA. S-[C]RT patients reported statistically and clinically significant worse fatigue and head and neck pain compared to [C]RT and SA patients at 3 months, but normalized at 1 year. S-CRT compared to S-RT had statistically and clinically worse physical and role functioning and swallowing difficulties at 3 months but this difference was resolved by 1-year posttreatment. CONCLUSION: HPV + OPSCC patients after SA report the lowest posttreatment QOL impact, whereas after S-CRT report the highest symptom burden. Careful selection for definitive surgery is important given the possibility of adjuvant CRT. Patients can experience persistent sense taste and smell difficulties at 1 year with all treatment modalities. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1687-1695, 2024.

The neutrophil-to-lymphocyte ratio in salivary gland cancers treated with pembrolizumab.

BACKGROUND: A minority of patients with recurrent/metastatic (R/M) salivary gland cancers (SGCs) benefit from immune checkpoint inhibitors (ICIs), necessitating reliable biomarkers for ICI response prediction. METHODS: Retrospective observational study of R/M SGC patients treated with pembrolizumab between 2016 and 2022, with a primary outcome of 6-month progression-free survival (PFS) and secondary outcome of 2-year overall survival (OS). Univariate and multivariable Cox proportional hazards models were employed. RESULTS: Twenty R/M SGC patients were included. After adjustment, NLR as a continuous variable was independently associated with 6-month PFS (HR 1.30, 95% CI 1.10-1.54, p = 0.002) and 2-year OS (HR 1.33, 95% CI 1.07-1.66, p = 0.010). Similarly, NLR ≥ 5 was associated with higher hazards of progression at 6 months (HR 12.85, 95% CI 2.17-76.16, p = 0.005) and death at 2 years (HR 11.25, 95% CI 1.67-75.77, p = 0.013). CONCLUSIONS: Higher pretreatment NLR was independently associated with inferior 6-month PFS and 2-year OS in pembrolizumab-treated R/M SGC patients.

Circulating tumor HPV DNA assessments after surgery for human papilloma virus-associated oropharynx carcinoma.

PURPOSE: To understand the utility of circulating tumor human papillomavirus DNA (ctHPVDNA) blood testing for HPV-associated oropharynx squamous cell carcinoma (HPV + OPSCC) after definitive surgery. MATERIALS AND METHODS: Prospective cohort study of HPV(+)OPSCC patients with ctHPVDNA test data to assess its accuracy in detecting biopsy-confirmed disease at various post-treatment time points. Eligible patients had p16(+)/HPV(+) OPSCC and ctHPVDNA testing performed at any time pre-operatively and/or postoperatively. In cases of recurrence, patients were excluded from analysis if ctHPVDNA testing was not performed within 6 months of biopsy. RESULTS: 196 all-treatment-type patients had at least one PT ctHPVDNA test. The initial post-treatment (PT) ctHPVDNA sensitivity, specificity, PPV, and NPV were 69.2 % (9/13), 96.7 % (177/183), 60.0 % (9/15), and 97.8 % (177/181). 61 surgery alone (SA) patients underwent 128 PT tests. The initial PT SA ctHPVDNA sensitivity, specificity, PPV, and NPV were 100 % (2/2), 96.0 % (48/50), 50 % (2/4), and 100 % (48/48). 35 of 61 (57.4 %) SA patients had NCCN-based histopathologic indications for adjuvant (chemo)radiation but declined. 3 of 35 (8.57 %) had a positive PT ctHPVDNA test of which 1 of 3 (33 %) had biopsy-proven recurrence. Prospectively, ten patients had a PreT positive ctHPVDNA, underwent SA, refused adjuvant treatment, had an undetectable ctHPVDNA within 2 weeks of SA, and remained free of disease (mean 10.3 months). CONCLUSION: The high specificity and NPV of ctHPVDNA after SA suggest ctHPVDNA may have a role in determining the omission of PT adjuvant (chemo)radiation in select patients.

Human Papillomavirus-Associated Oropharyngeal Cancer: Global Epidemiology and Public Policy Implications.

Global trends in human papillomavirus (HPV)-associated head and neck cancers (HNC), specifically in the oropharynx subsite, have been dynamically changing, leading to new staging and treatment paradigms. Epidemiologic studies have noted regional variations in HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). While HPV vaccination remains the main preventative approach, vaccination policy in relation to gender neutrality is heterogeneous and particularly sparse in low- and middle-income countries, where the burden of global cancer cases and HPV-associated HNC are not well-characterized in certain regions. This review summarizes the existing literature on regional variations of HPV-associated OPSCC and gender-neutral vaccine policies. Based on available data, the incidence of HPV-associated OPSCC is highest in North America, Europe, and Oceania. As of 2022, 122 of 195 (63%) World Health Organization (WHO) member states had incorporated HPV vaccinations nationally; of these, 41 of 122 (34%) member states have introduced gender-neutral vaccine coverage. Future research is needed to describe continued evolving trends in HPV-associated OPSCC, understand underlying risk factors leading to regional variation in disease, and implement gender-neutral policy more broadly.

Transcriptional space-time mapping identifies concerted immune and stromal cell patterns and gene programs in wound healing and cancer.

Tissue repair responses in metazoans are highly coordinated by different cell types over space and time. However, comprehensive single-cell-based characterization covering this coordination is lacking. Here, we captured transcriptional states of single cells over space and time during skin wound closure, revealing choreographed gene-expression profiles. We identified shared space-time patterns of cellular and gene program enrichment, which we call multicellular "movements" spanning multiple cell types. We validated some of the discovered space-time movements using large-volume imaging of cleared wounds and demonstrated the value of this analysis to predict "sender" and "receiver" gene programs in macrophages and fibroblasts. Finally, we tested the hypothesis that tumors are like "wounds that never heal" and found conserved wound healing movements in mouse melanoma and colorectal tumor models, as well as human tumor samples, revealing fundamental multicellular units of tissue biology for integrative studies.

A prospective evaluation of neck and shoulder function following treatments of early-stage human papillomavirus-associated oropharynx cancer.

OBJECTIVES: To compare post-treatment neck and shoulder function between human papillomavirus-associated oropharynx squamous cell carcinoma (HPV + OPSCC) treatments. DESIGN: Prospective, repeated-measures study. SETTING: Tertiary care center. PARTICIPANTS: Treatment-naïve patients with American Joint Committee on Cancer eighth edition stage T0-3/N0-2 HPV+OPSCC. MAIN OUTCOME MEASURES: Patients completed the Neck Dissection Impairment Index (NDII) pre-treatment and 3-months and 1-year post-treatment. The NDII assesses 10 neck and shoulder functions scored 0-5 (total score 0-100), with higher scores suggesting better function. RESULTS: A total of 106 patients underwent: surgery alone (SA, n = 46, 43%), surgery with adjuvant radiation ± chemotherapy (S + a[C]XRT, n = 18, 17%), or definitive radiation ± chemotherapy (d[C]XRT, n = 42, 40%). cTN classification and pre-treatment NDII scores did not differ between groups. SA patients reported worsened 3-month post-treatment versus pre-treatment self-care (4.6 vs. 5.0), lifting light (4.6 vs. 5.0) and heavy (4.2 vs. 4.8) objects, overhead reach (4.5 vs. 4.9), activity (4.5 vs. 4.9), socialization (4.7 vs. 4.9), recreation (4.6 vs. 4.9), and overall score (86.8 vs. 95.3) (all p < 0.05). One-year post-treatment scores (n = 34) were no different than pre-treatment in all domains. S + a[C]XRT patients reported worsened 3-month versus pre-treatment stiffness (4.0 vs. 4.8), lifting heavy objects (3.8 vs. 4.9), overhead reach (4.2 vs. 4.9), socialization (4.6 vs. 5.0), recreation (4.4 vs. 4.9) and overall score (82.4 vs. 96.0) (all p < 0.05). One-year post-treatment scores (n = 13) were no different than pre-treatment in all domains. d[C]XRT patients reported worsened 3-month versus pre-treatment difficulty lifting heavy objects (4.3 vs. 4.7) and recreation (4.3 vs. 4.7). One-year posttreatment scores (n = 21) were no different than pre-treatment in all domains. CONCLUSION: HPV + OPSCC patients may experience mild shoulder/neck dysfunction 3 months after treatment that usually resolves by 1 year, independent of treatment modality.

Prospective quality of life outcomes for human papillomavirus associated oropharynx cancer patients after surgery alone.

PURPOSE: To evaluate changes in patient-reported quality of life (QOL) to inform treatment decisions for human papillomavirus-associated oropharynx squamous cell carcinoma (HPV + OPSCC). MATERIALS AND METHODS: Patients with American Joint Committee on Cancer (AJCC) 8th edition cT0-T3 and cN0-N3 HPV + OPSCC treated with transoral robotic surgery to the primary site with neck dissection completed questionnaires prior to surgery and at three-months and one-year post-operatively. Questionnaires included four validated instruments: the University of Washington Quality of Life Questionnaire (UW-QOL), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and Head and Neck Module (HN35), and the Neck Dissection Impairment Index (NDII). RESULTS: Forty-eight patients filled out pretreatment and three-month questionnaires. 37 patients filled out one-year questionnaires. With the UW-QOL, at three-months, patients reported a statistically significant and clinically meaningful decreased mean score for appearance that resolved at one-year (presurgery: 92.4, 3-month: 81.0, p < 0.001; one year: 86.5). At three months and one-year, significant and clinically meaningful decreased mean taste scores persisted (presurgery: 98.0; three-months: 76.3, one-year: 80.3; all p < 0.001). With the EORTC QLQ-C30 and HN35, at one-year, only mean scores for sense of taste or smell (one-year: 13.1; p < 0.001) did not return to baseline. With the NDII, patients returned to functions comparable to baseline in all domains. CONCLUSION: Post-treatment quality of life is high for HPV+ OPSCC patients treated with surgery alone. Mild taste and possibly smell dysfunction may continue in some patients. With careful selection, surgery alone for HPV + OPSCC offers favorable QOL outcomes. LAY SUMMARY: Patients with HPV+ associated oropharynx cancer treated with surgery alone completed quality of life questionnaires before and after surgery. Quality of life remained high for most patients, with a subset of patients experiencing mild taste dysfunction one-year after surgery.

Dynamic CD8+ T cell responses to cancer immunotherapy in human regional lymph nodes are disrupted in metastatic lymph nodes.

CD8+ T cell responses are critical for anti-tumor immunity. While extensively profiled in the tumor microenvironment, recent studies in mice identified responses in lymph nodes (LNs) as essential; however, the role of LNs in human cancer patients remains unknown. We examined CD8+ T cells in human head and neck squamous cell carcinomas, regional LNs, and blood using mass cytometry, single-cell genomics, and multiplexed ion beam imaging. We identified progenitor exhausted CD8+ T cells (Tpex) that were abundant in uninvolved LN and clonally related to terminally exhausted cells in the tumor. After anti-PD-L1 immunotherapy, Tpex in uninvolved LNs reduced in frequency but localized near dendritic cells and proliferating intermediate-exhausted CD8+ T cells (Tex-int), consistent with activation and differentiation. LN responses coincided with increased circulating Tex-int. In metastatic LNs, these response hallmarks were impaired, with immunosuppressive cellular niches. Our results identify important roles for LNs in anti-tumor immune responses in humans.

Human Papillomavirus-Associated Head and Neck Malignancies in Sub-Saharan Africa: A Systematic Review.

PURPOSE: The proportion of head and neck cancers (HNCs) with human papillomavirus (HPV) positivity in sub-Saharan Africa (SSA) is poorly characterized. Characterizing this has implications in staging, prognosis, resource allocation, and vaccination policies. This study aims to determine the proportion of HPV-associated HNC in SSA. MATERIALS AND METHODS: This systematic review included searches from PubMed, EMBASE, Web of Science, African Index Medicus, Google Scholar, and African Journals Online. All English publications reporting the proportion of HNC specimens from SSA patients who tested positive for HPV and/or p16 were included. Study quality was assessed using the National Institutes of Health Quality Assessment Tool for Case Series Studies. RESULTS: In this systematic review of 31 studies and 3,850 patients, the overall p16 positivity was 13.6% (41 of 1,037 patients tested) with the highest proportion among oropharyngeal cancers (20.3%, 78 of 384 patients) and the overall HPV polymerase chain reaction positivity was 15.3% (542 of 3,548 samples tested) with the highest proportion among nasopharyngeal cancers (16.5%, 23 of 139 patients). Among the 369 HPV strains detected, the most common genotypes were HPV 16 (226 patients, 59.2%) and HPV 18 (78, 20.4%). CONCLUSION: HPV was found to be associated with a significant proportion of HNC in SSA. The genotypes reported suggest that the nine-valent vaccine and gender-neutral vaccination policies should be considered. Given that these studies may not accurately capture prevalence nor causation of HPV in HNC subsites, additional research is needed to provide a more thorough epidemiologic understanding of HPV-associated HNC in SSA, including risk factors and clinical outcomes.

Patterns of Postoperative Trismus Following Mandibulectomy and Fibula Free Flap Reconstruction.

The factors that contribute to postoperative trismus after mandibulectomy and fibula free flap reconstruction (FFFR) are undefined. We retrospectively assessed postoperative trismus (defined as a maximum interincisal opening ≤35 mm) in 106 patients undergoing mandibulectomy with FFFR, employing logistic regression to identify risk factors associated with this sequela. The surgical indication was primary ablation in 64%, salvage for recurrence in 24%, and osteonecrosis in 12%. Forty-five percent of patients had existing preoperative trismus, and 58% of patients received adjuvant radiation/chemoradiation following surgery. The overall rates of postoperative trismus were 76% in the early postoperative period (≤3 months after surgery) and 67% in the late postoperative period (>6 months after surgery). Late postoperative trismus occurred more frequently in patients with ramus-involving vs. ramus-preserving posterior mandibulotomies (82% vs. 46%, p = 0.004). A ramus-involving mandibulotomy was the only variable significantly associated with trismus >6 months postoperatively on multivariable logistic regression (OR, 7.94; 95% CI, 1.85−33.97; p = 0.005). This work demonstrates that trismus is common after mandibulectomy and FFFR, and suggests that posterior mandibulotomies that involve or remove the ramus may predispose to a higher risk of persistent postoperative trismus.

Longitudinal Analysis of Swallowing Displacement Kinematics After Oropharyngeal Cancer Treatment.

BACKGROUND/OBJECTIVE: Quantitative swallowing displacement kinematics evolve in patients treated for oropharyngeal squamous cell carcinoma (OPSCC). We aimed to longitudinally assess these measurements and correlate them with functional swallowing outcomes. METHOD: A retrospective review was conducted on patients with OPSCC treated with definitive (chemo)radiation ([C]RT) or surgery with adjuvant (chemo)radiation (S-[C]RT) who completed at least two videofluoroscopic swallow studies (VFSS). Longitudinal analysis was accomplished via mixed-effects logistic regression for the Functional Oral Intake Scale (FOIS), and Penetration Aspiration Scale (PAS), and mixed-effects linear regression for kinematic measures. Spearman's correlation was conducted between changes in FOIS/PAS and kinematic measures. RESULTS: Ninety-seven patients (76 males; mean age 61) completed 245 VFSS studies. A total of 94% had human papillomavirus (HPV)/p16 positive OPSCC and 74% were T0-T2. Sixty-four patients underwent [C]RT while 33 patients underwent S-[C]RT. After treatment, posterior pharyngeal wall at hold (PPWhold) increased 3.2 standard deviation (SD) between 0 and 6 months (p < 0.001), then decreased 2.2 SD between 6 and 12 months (p < 0.001) and did not return to baseline. Hyoid-to-larynx (HL) (p = 0.046) and maximal hyoid displacement (Hmax) + HL (p = 0.042) increased between 6 and 12 months. Hmax (p = 0.020) and Hmax + HL (p < 0.001) decreased between 12-24 months beyond baseline values. The decrease in HL and increase in PPWhold (p < 0.05) correlated with an increase in PAS. From baseline, increased pharyngeal constriction ratio correlated with decreased FOIS and PPWhold (p < 0.05). CONCLUSIONS: Quantitative swallowing kinematic measures can effectively track changes in swallowing physiology. Increased PPWhold and restricted hyolaryngeal movement were seen in patients with OPSCC after treatment and correlated with a change in swallowing outcome, emphasizing the need for serial VFSS monitoring and targeted intervention. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1339-1348, 2023.

Relations of Current and Past Cancer with Severe Outcomes among 104,590 Hospitalized COVID-19 Patients: The COVID EHR Cohort at the University of Wisconsin.

BACKGROUND: There is mixed evidence about the relations of current versus past cancer with severe COVID-19 outcomes and how they vary by patient and cancer characteristics. METHODS: Electronic health record data of 104,590 adult hospitalized patients with COVID-19 were obtained from 21 United States health systems from February 2020 through September 2021. In-hospital mortality and ICU admission were predicted from current and past cancer diagnoses. Moderation by patient characteristics, vaccination status, cancer type, and year of the pandemic was examined. RESULTS: 6.8% of the patients had current (n = 7,141) and 6.5% had past (n = 6,749) cancer diagnoses. Current cancer predicted both severe outcomes but past cancer did not; adjusted odds ratios (aOR) for mortality were 1.58 [95% confidence interval (CI), 1.46-1.70] and 1.04 (95% CI, 0.96-1.13), respectively. Mortality rates decreased over the pandemic but the incremental risk of current cancer persisted, with the increment being larger among younger vs. older patients. Prior COVID-19 vaccination reduced mortality generally and among those with current cancer (aOR, 0.69; 95% CI, 0.53-0.90). CONCLUSIONS: Current cancer, especially among younger patients, posed a substantially increased risk for death and ICU admission among patients with COVID-19; prior COVID-19 vaccination mitigated the risk associated with current cancer. Past history of cancer was not associated with higher risks for severe COVID-19 outcomes for most cancer types. IMPACT: This study clarifies the characteristics that modify the risk associated with cancer on severe COVID-19 outcomes across the first 20 months of the COVID-19 pandemic. See related commentary by Egan et al., p. 3.

Approaches to the Management of Metastatic Adenoid Cystic Carcinoma.

High rates of recurrence and distant metastasis are a foremost challenge in the management of adenoid cystic carcinoma (ACC), occurring in approximately 40% of all ACC patients. Despite the morbidity and mortality resulting from recurrent/metastatic (R/M) disease, there are no FDA-approved systemic agents for these patients. In this review, we summarize pertinent ACC pathophysiology and its implications for different systemic treatment regimens in R/M ACC. We review the evidence for the most widely used systemic agents - cytotoxic chemotherapy and tyrosine kinase inhibitors (TKIs) targeting VEGFR - in addition to immune checkpoint inhibitors and non-TKI biologic agents. Exciting emerging targets for R/M ACC, including inhibitors of Notch signaling, stemness, PRMT5, and Axl, are also discussed. Lastly, we review local therapies for small-volume lung disease in patients with oligometastatic ACC, specifically pulmonary metastasectomy and stereotactic body radiation therapy (SBRT). Future development of targeted molecular agents which exploit the underlying biology of this disease may yield novel therapeutic options to improve clinical outcomes in patients with R/M ACC.