Revisiting Feeding Tube Utilization in Oropharynx Cancer: 6-Year Prospective Registry Analysis.

OBJECTIVE: Patients treated for oropharyngeal cancer (OPC) have historically demonstrated high feeding tube rates for decreased oral intake and malnutrition. We re-examined feeding tube practices in these patients. STUDY DESIGN: Retrospective analysis of prospective cohort from 2015 to 2021. SETTING: Single-institution NCI-Designated Comprehensive Cancer Center. METHODS: With IRB approval, patients with new oropharyngeal squamous cell cancer or (unknown primary with neck metastasis) were enrolled. Baseline swallowing was assessed via videofluoroscopy and Performance Status Scale for Head and Neck Cancer (PSSHN). G-tubes or nasogastric tubes (NGT) were placed for weight loss before, during, or after treatment. Prophylactic NGT were placed during transoral robotic surgery (TORS). Tube duration was censored at last disease-free follow-up. Multivariate regression was performed for G-tube placement (odds ratio [OR] [95% confidence interval [CI]) and removal (Cox hazard ratio, hazard ratio [HR] [95% CI]). RESULTS: Of 924 patients, most had stage I to II (81%), p16+ (89%), node-positive (88%) disease. Median follow-up was 2.6 years (interquartile range 1.5-3.9). Most (91%) received radiation/chemoradiation, and 16% received TORS. G-tube rate was 27% (5% after TORS). G-tube risk was increased with chemoradiation (OR 2.78 [1.87-4.22]) and decreased with TORS (OR 0.31 [0.15-0.57]) and PSSHN-Diet score ≥60 (OR 0.26 [0.15-0.45]). G-tube removal probability over time was lower for T3 to T4 tumors (HR 0.52 [0.38-0.71]) and higher for PSSHN-Diet score ≥60 (HR 1.65 [1.03-2.66]). CONCLUSIONS: In this modern cohort of patients treated for OPC, 27% received G-tubes-50% less than institutional rates 10 years ago. Patients with preserved baseline swallowing and/or those eligible for TORS may have lower G-tube risk and duration.

Neoadjuvant cemiplimab and surgery for stage II-IV cutaneous squamous-cell carcinoma: follow-up and survival outcomes of a single-arm, multicentre, phase 2 study.

BACKGROUND: We previously reported rates of pathological complete responses (51% [95% CI 39-62] per independent central review, the primary endpoint) and major pathological responses (13% per independent central review, a secondary endpoint) to neoadjuvant cemiplimab (an anti-PD-1 inhibitor) among 79 patients with locoregionally advanced, resectable cutaneous squamous cell carcinoma. Here, we present follow-up data, including event-free, disease-free, and overall survival. METHODS: This single-arm, multicentre, phase 2 study included patients aged 18 years or older with resectable stage II-IV (M0) cutaneous squamous cell carcinoma and Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received up to four planned doses of neoadjuvant cemiplimab 350 mg intravenously every 3 weeks followed by curative-intent surgery. After surgery, per investigator discretion, patients received either adjuvant cemiplimab for up to 48 weeks, radiotherapy, or observation alone. Secondary endpoints included in this follow-up analysis are event-free survival, disease-free survival, and overall survival, all summarised using the Kaplan-Meier method. Activity and safety endpoints were analysed for all enrolled patients who received at least one dose of neoadjuvant cemiplimab. In this report, safety data are reported for all patients who received at least one dose of adjuvant cemiplimab. This trial is registered with ClinicalTrials.gov, NCT04154943, has completed enrolment and follow-up is ongoing. FINDINGS: Between March 20, 2020, and July 8, 2021, 79 patients were enrolled. Median age was 73 years (IQR 66-81), 67 (85%) patients were male, 12 (15%) were female, 69 (87%) were White, one was Asian (1%), one was other race (1%), and race was not reported for eight (10%). As of data cutoff (Dec 1, 2022), median follow-up was 18·7 months (IQR 15·6-22·1) for all 79 patients. Among 70 patients who had surgery, 65 (93%) had post-surgical management data: 32 (49%) of 65 were observed postoperatively, 16 (25%) received adjuvant cemiplimab, and 17 (26%) received adjuvant radiotherapy. 11 (14%) of 79 patients had event-free survival events, with an estimated 12-month event-free survival of 89% (95% CI 79-94) for all patients. None of 40 patients who had a pathological complete response and one (10%) of ten patients with major pathological response had recurrence. Six (9%) of 70 patients who completed surgery had a disease-free survival event, with an estimated 12-month disease-free survival of 92% (95% CI 82-97). Nine (11%) of 79 patients died, with an estimated 12-month overall survival for all patients of 92% (95% CI 83-96). Four (25%) of 16 patients who received adjuvant cemiplimab treatment had grade 3 adverse events, including one (6%) who had increased blood potassium, one (6%) who had traumatic limb amputation, and two who had serious adverse events (one [6%] cardiomyopathy and one [6%] hypophysitis). There were no grade 4 adverse events or treatment-related deaths. INTERPRETATION: For patients with resectable stage II-IV cutaneous squamous cell carcinoma, neoadjuvant cemiplimab followed by surgery might be a potential treatment option, addressing a substantial unmet need. FUNDING: Regeneron Pharmaceuticals and Sanofi.

High Notch1 expression affects chemosensitivity of head and neck squamous cell carcinoma to paclitaxel and cisplatin treatment.

BACKGROUND: Notch1 expression has been reported to be associated with chemotherapy resistance and poor prognosis, but the role of Notch1 in head and neck squamous cell carcinoma (HNSCC) sensitivity to anticancer drugs remains unclear. The aim of this study was to evaluate HNSCC sensitivity to paclitaxel and cisplatin in vitro and the chemotherapeutic response of HNSCC to these two drugs in vivo. METHODS: We used immunohistochemistry to assess Notch1 expression in fresh HNSCC samples treated by PF (cisplatin+5- fluorouracil) and TPF (paclitaxel + cisplatin+5- fluorouracil). We also assessed the sensitivity of two HNSCC cell lines to the Notch1 inhibitor of N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT). The overall and progression-free survival were assessed. RESULTS: High Notch1 expression was significantly associated with paclitaxel resistance (P < 0.01). DAPT increased sensitivity to paclitaxel and cisplatin in vitro (P < 0.05). Compared with patients with Notch1 expression, patients without Notch1 expression were more likely to have a response to neoadjuvant chemotherapy with PF (P < 0.01) or TPF (P < 0.01) and had significantly better overall survival (P < 0.05) and progression-free survival (P < 0.05). Among patients without Notch1 expression (but not among patients with Notch1 expression), those who received TPF had significantly better survival than those who received PF (P < 0.05). CONCLUSION: Taken together, our findings may provide some evidence to partially support the predictive value of Notch1 expression in the therapeutic response to paclitaxel and cisplatin.

Effect of Tumor Size and Minimal Extrathyroidal Extension in Patients with Differentiated Thyroid Cancer.

INTRODUCTION: Risk-stratified treatment strategies have become a focus in the treatment of differentiated thyroid cancer (DTC). In the 2015 American Thyroid Association treatment guidelines, adjuvant treatment with radioactive iodine (RAI) is considered in the presence of minimal extrathyroidal extension (mETE). This study aimed to investigate the prognostic significance of mETE and tumor size in patients with DTC. METHODS: A retrospective review was undertaken of 2323 consecutive patients treated surgically for T1-T3 (defined per seventh edition of the American Joint Committee on Cancer staging criteria) and M0 DTC from 2000 to 2015 at The University of Texas MD Anderson Cancer Center. Patients were divided into four groups according to the size of the tumor (≤4 cm vs. >4 cm) and the presence of mETE. Predictors of disease-free survival (DFS), disease-specific survival, locoregional failure (LRF), and distant metastatic failure (DMF) were compared using the log-rank test and Cox's proportional hazards models. RESULTS: There were only seven DTC-related deaths, limiting the clinical significance of the analysis, especially of overall and disease-specific survival. Following multivariate analysis, patients with tumors >4 cm did worse than patients with tumors ≤4 cm with respect to DFS (group 3 [>4 cm without mETE] adjusted hazard ratio (HRadj) = 2.1 [confidence interval (CI) 1.1-3.8]; group 4 [>4 cm with mETE] HRadj = 2.9 [CI 1.6-5.1]). However, patients did not differ according to DFS, regardless of the presence of mETE within each size category (group 2 [≤4 cm with mETE] vs. group 1 [≤4 cm without mETE] HRadj = 1.3 [CI 0.9-1.8]; group 4 [>4 cm without mETE] vs. group 3 [>4 cm with mETE] HRadj = 1.0 [CI 0.5-2.3]). For LRF and DMF, size but not mETE was also an independent risk factor. CONCLUSION: Tumor size, but not the presence of mETE, was an independent predictor of DFS, LRF, and DMF in DTC.