Objective The effects of sex hormones remain largely unexplored in pheochromocytomas and paragangliomas (PPGLs) and gastroenteropancreatic neuroendocrine tumors (GEP-NETs).Methods We evaluated the effects of estradiol, progesterone, Dehydroepiandrosterone sulfate (DHEAS), and testosterone on human patient-derived PPGL/GEP-NET primary culture cell viability (n = 38/n = 12), performed next-generation sequencing and immunohistochemical hormone receptor analysis in patient-derived PPGL tumor tissues (n = 36).Results In PPGLs, estradiol and progesterone (1 mu m) demonstrated overall significant antitumor effects with the strongest efficacy in PPGLs with NF1 (cluster 2) pathogenic variants. Estrogen receptor alpha (ER alpha) positivity was detected in 11/36 PPGLs, including 4/4 head-and-neck paragangliomas (HNPGLs). ER alpha-positive tumors responded with a significant cell viability decrease to estradiol. DHEAS and testosterone (1 mu m) displayed no effects, but higher doses of testosterone (10 mu m) demonstrated significant antitumor effects, including a pheochromocytoma lung metastasis with strong androgen receptor positivity (30%). Driven by the antitumor effects of estrogen, we evaluated G-protein-coupled estrogen receptor (GPER) agonist G-1 as a potential therapeutic option for PPGLs and found strong significant antitumor potential, with the strongest efficacy in tumors with NF1 pathogenic variants. Moreover, we detected sex-related differences-tumors from male patients showed significantly stronger responsivity to G-1 compared with tumors from female patients. In GEP-NETs, sex hormones showed overall no effects, especially no tumor growth-promoting effects.Conclusion We provide novel data on the effects of elevated sex hormone levels, potentially seen during pregnancy or hormone replacement therapy, on PPGL/GEP-NET tumor growth. G-1 might offer a novel therapeutic approach for some PPGLs depending on patient's sex and the individual tumor's genetic/molecular background. All HNPGLs showed ER alpha positivity.

CONTEXT:Pheochromocytomas and paragangliomas (PPGLs) are rare endocrine tumors that frequently produce catecholamines. Catecholamine-induced cardiometabolic complications substantially contribute to increased morbidity and mortality in PPGL patients prior to surgical resection. OBJECTIVE:To determine whether markers of elevated cardiometabolic risk persist in patients following PPGL resection. METHODS:In this retrospective analysis of a multicenter cohort of patients with PPGLs participating in the prospective ProsPheo study and the ENS@T registry, cardiometabolic risk factors, including glycemic status, dyslipidemia, and body mass index (BMI), were assessed in patients with PPGL at diagnosis and during follow-up. Patients with a history of resected PPGL were compared to a control group with nonfunctioning adrenal adenomas from the ENS@T registry. RESULTS:Patients with a present PPGL or a history of PPGL (n = 188), a metastatic PPGL (n = 27), or a known susceptibility gene pathogenic variant (PV) for the development of PPGL without a history of PPGL (n = 44) were included. We compared the asymptomatic PV carriers to patients with a history of PPGL: those with a history of PPGL showed a significantly higher prevalence of hyperglycemic disorders (P = .013) compared with asymptomatic PV carriers. In patients with a history of PPGL and at least 12 months of follow-up post surgery (n = 113), the prevalence of hyperglycemic disorders (P < .001), as well as the mean HbA1c (5.63%, SD 0.43%), were significantly higher, compared to a control group with nonfunctioning adrenal adenomas (n = 76) of similar age and BMI (HbA1c 5.45%, SD 0.40%; P = .004). CONCLUSION:Glycemic disturbances persist long-term after the resection of PPGL.

We report a case of a 54-year-old patient diagnosed with T1N0M0 oral squamous cell cancer located at the right maxillary tuberosity. The treatment plan included wide local excision with partial maxillectomy and sentinel lymph node biopsy. Preoperative single photon emission computed tomography/computed tomography (SPECT/CT) revealed lymphatic drainage to a single ipsilateral retropharyngeal lymph node (Rouvière's node/level VIIa). Due to the poor surgical accessibility of this lymph node, the decision was made to proceed with the tumor resection without sentinel lymph node excision, focusing instead on assessing the tumor's depth of infiltration to estimate the risk of metastasis. Histopathological analysis of the specimen confirmed clear margins with 2mm depth of infiltration. Consequently, the patient was placed under observation. This case represents the first reported instance of sentinel lymph node drainage to Rouvière's node in early oral squamous cell carcinoma, presenting a unique diagnostic and therapeutic challenge.

Objective Molecular testing is a well-established tool that assists in the management of thyroid nodules. We describe our experience using molecular testing of thyroid nodules with Bethesda III to VI cytology. Methods This is a retrospective multicenter, multinational study of thyroid nodules that underwent preoperative molecular profiling with ThyGenX/ThyGeNEXT or ThyroSeq V3 between 2015 and 2022. The clinical characteristics and mutational profiles of tumors were compared. Collected data included demographics, cytology results, surgical pathology, and molecular alterations. Molecular alterations were categorized into 3 main phenotypes: BRAF-like, RAS-like, and non-BRAF-non-RAS (NBNR). Results Overall, 784 patients who had surgery were included, of which 603 (76.2%) were females. The most common histologic type was papillary thyroid cancer (PTC) with 727 (91.9%) cases. In total, 205 (28.2%) cases showed an aggressive subtype of PTC (eg, tall cell and hobnail). BRAF-like alterations were most likely to be found in Bethesda V and VI nodules and show extrathyroidal extension (ETE), nodal disease, and/or aggressive subtypes of PTC (P < .001 for all). RAS-like alterations were more commonly found in Bethesda III and IV nodules and were less likely to show ETE, nodal disease, and/or aggressive histology (P < .001 for all). NBNR alterations were more commonly found in Bethesda III and IV nodules and were less likely to show ETE, nodal disease, and/or aggressive subtypes of PTC. However, they were rarely but significantly associated with poorly differentiated thyroid cancer (P < .005). Conclusion Molecular testing of thyroid nodules can help determine the likelihood of malignancy and classify nodules into several tumor phenotypes, predicting their behaviors and potentially allowing for a more tailored treatment. NBNR alterations should be managed with caution.

Purpose The current established technique for sentinel lymph node (SLN) biopsy is preoperative injection of 99m technetium-labeled nanosized colloids ( 99m Tc) followed by single photon emission computed tomography and standard computed tomography (SPECT/CT) with subsequent intraoperative gamma probe-guided excision of the SLN. It is however time and resource consuming, causes radiation exposure and morbidity for the patient as the injection is done in the awake patient. Recently near-infrared imaging with indocyanine green (ICG) gained importance in SLN biopsy as a faster and more convenient technique. The objective of our study was to investigate the feasibility of SLN biopsy using ICG-imaging in early oral squamous cell carcinoma (OSCC). Methods Single-centre pilot study of five patients with early-stage OSCC. For all patients, both techniques ( 99m Tc and ICG) were performed. We injected 99m Tc preoperatively in the awake patient, followed by SPECT/CT imaging. Intraoperatively ICG was injected around the primary tumor. Then the neck incision was performed according to the SPECT/CT images and SLN were detected by using a gamma probe and near-infrared fluorescence imaging of the ICG-marked lymph nodes intraoperatively. The excised lymph nodes were sent to histopathological examination according to the SLN dissection protocol. Results In all five patients sentinel lymph nodes were identified. A total of 7 SLN were identified after injection of 99m Tc, imaging with SPECT/CT and intraoperative use of a gamma probe. All these SLN were fluorescent and visible with the ICG technique. In two patients, we could identify additional lymph nodes using the ICG technique. Pathological analysis demonstrated occult metastasis in two of the cases. Conclusions Our study shows that ICG-guided SLN biopsy is a feasible technique, especially in combination with conventional radioisotope method and may help for intraoperative localization of SLN. Validation studies with bigger patient cohorts are needed to prove our results.

We therefore felt appropriate to evaluate the potential role of the non-FDG tracer 18 F-choline in imaging of salivary gland tumors.Our goal was to evaluate the added value of a potentially more specific radiotracer. MethodsAfter obtaining ethics review board approval and informed consent of the patients, we prospectively included patients with clinical and cytological strong suspicion of malignant salivary gland tumors.All patients underwent hybrid FDG-PET followed by hybrid choline-PET.Surgery was offered as a primary treatment modality in resectable cases.Surgical pathology was reviewed by a dedicated head and neck pathologist (NJR) and classified pursuant to the 2017 update of the WHO classification [3]. ResultsThe cohort included five prospectively enrolled patients (Table 1).Four cases had cytologically proven malignant (Milan category VI) salivary gland neoplasms.In addition, one case of cytological "salivary gland neoplasm of uncertain malignant potential" (SUMP; Milan category IVb) was included [7].On final pathology, one case was a parotid gland highgrade mucoepidermoid carcinoma, one case of classical (low-grade) acinic cell carcinoma, one case of high-grade adenocarcinoma NOS, which would be classified as (high-grade) mucinous adenocarcinoma according to the forthcoming WHO 2023 classification.The other

Cinematic rendering represents a transformative technique, altering the manner in which radiologists and other medical specialists perceive anatomical details and pathological conditions.Developed as a fusion of radiology and cinematography, cinematic rendering transcends traditional rendering methods, providing lifelike representations that bridge the gap between medical images and reality [1].Cinematic rendering is a post-processing technique rooted in the segmentation of standard radiological images into photorealistic three-dimensional representations,

Background: Oncocytic thyroid carcinoma (OTC) was previously considered a variant of follicular thyroid carcinoma (FTC) but has recently been reclassified as a separate form of thyroid cancer. This study aimed to demonstrate that FTC and OTC are fundamentally distinct entities that can potentially be differentiated preoperatively through cytology and/or molecular testing. Methods: A retrospective chart review of patients diagnosed with FTC and OTC operated upon at two university health centers from January 2016 to September 2023 (n = 3219) was conducted. Molecular testing results were correlated with histopathologic diagnosis. Results: Fifty patients met the inclusion criteria. FTC was identified in 27 (54.0%) patients, and OTC in 23 (46.0%) patients. Patients with OTC were older (61.8 years) than FTC patients (51.2 years) (p = 0.013). Moreover, aggressive tumors were found in 39.1% (9/23) of OTCs compared to 11.1% (3/27) of FTCs (p = 0.021). Amongst Bethesda category III and IV nodules, 17 out of 20 (85.0%) OTC cytology reports demonstrated an oncocytic subtype compared to only 5 out of 24 FTC cytology reports (20.8%) (p = 0.002). On molecular testing, the EIF1AX alteration was exclusively present in OTCs while the PAX8/PPARy and PTEN alterations were exclusively found in FTCs. Copy number alterations (CNAs) were found to be more prevalent in OTC (66.7%) compared to FTC (33.3%), and they were not indicative of tumor aggressiveness. Within the OTC group, all three patients who had a TP53 alteration were diagnosed with aggressive cancer. Lastly, the OTCs exhibited a higher frequency of multiple alterations on molecular testing (66.7%) compared to FTCs (33.3%). Conclusion: To our knowledge, this is the largest study to date comparing the clinical application of abnormalities found on molecular testing for FTC and OTC. It further demonstrates the distinct clinicopathological and molecular characteristics of OTC.

Purpose/Objective Approximately 70% of head and neck cancer (HNC) patients present with locoregionally advanced disease. The curative rate for early disease is 80-95%; for advanced tumors, locoregional recurrence rate remains at about 50-60% despite advances in treatment, and 20-30% will have distant metastases. Further, patients will develop a second primary malignancy (SPM) with a rate of 2-4% per year.Follow-up (FU) is important to detect recurrence (REC) and SPM at an early stage, to enable effective salvagetherapy, manage treatment-related sequelae, and provide functional rehabilitation and psychosocial support.In the absence of high-level evidence, there is no clear international consensus in FU regimens. There are only retrospective studies addressing this topic, mostly showing no difference in overall survival between patients with REC detected during routine FU and symptom-driven self-referral visits. The value of imaging is also subject of debate. Moreover, many of the hitherto published studies did not include the logistical, psychological and financial consequences and the relevant cost evaluations in today's healthcare systems facing increasing financial pressure.We propose a large multicenter, randomized prospective trial in HNC patients with complete remission 6 months after curative treatment to compare two FU schemes differing in frequency of scheduled clinical examinations and imaging. We hypothesize that implementing an individualized de-intensified FU with active patient involvement does not differ from a conventional regular FU in terms of death from any cause up to 5 years (=primary endpoint). We also hypothesize that symptom-driven self-referral FU visits have a higher diagnostic yield in detection of REC/SPM than regular scheduled clinical and radiological examinations. Consequently, we assume that fewer scheduled exams in well-instructed patients will not lead to worse outcome. The secondary objectives are the comparison of death from HNC and any cancer, detection of first REC/SPM, health-related quality of life, fear of recurrence, compliance with FU assessments, number of visits and HNC-specific health-care utilization.The objective of the herein presented Pilot 1 study was to assess the feasibility of patients’ recruitment, motivation for trial participation and compliance in completing a monthly, paper-based symptoms’ monitoring (patient-reported outcome [PRO], symptom tracker). This Pilot is supported by Swiss Cancer Research. Material/Methods The study design is shown in Figure 1 (RMST: restricted mean survival time).The main study is a randomized-controlled combined non-inferiority and superiority trial with explicit Pilot 1 and 2. After curative treatment, participants are randomized to an individualized de-intensified FU with monthly symptoms’ monitoring (Figure 2) (experimental arm) or to standard FU.Alerting symptoms possibly indicating REC/SPM or non-completion of the PROs will result in an urgent clinical FU appointment in the experimental arm. Minimal FU within Pilot 1 is 12 months (as opposed to 60 months in the main trial). Recruitment was done in three Swiss tertiary referral centers, which committed to enroll at least 20 patients during one year. Results The primary aim of Pilot 1, evaluating the feasibility of patient recruitment, has been confirmed faster than expected (20 committed patients randomized after 7 and 29 patients randomized after 11 months accrual time, respectively). Six unscheduled visits were triggered by our paper-based PRO. Within Pilot 1, a prescreening survey was conducted to better understand the specific motivation of patients to participate in the trial or not. We surveyed 41 potential participants of which 27 (66%) agreed to participate. The potential reduction in imaging was the main reason for the patients to participate in the trial (52%). Additionally, we collected feedback on the design of the paper-based PRO questionnaire at the 6-month FU visit when participants had already gained some experience. Participants expressed that the PRO questionnaire was easy to understand and comprehensive, thus facilitating them to communicate with their corresponding study center. The completion time for the PRO was between 5-10 minutes in 63% of the participants. In addition, 63% of the patients were in favor of transitioning the paper-based PRO to an electronic version (ePRO), the other 37% felt unsure about using an ePRO. Interim compliance data will be presented. Conclusion The recruitment and symptoms’ monitoring for HNC patients have been proofed as feasible. Pilot 2 is in planning to allow for a smooth continuation of Pilot 1 with following specific goals: 1) to expand the trial to 12 Swiss and 4 European sites; 2) to recruit up to 200 participants; 3) to implement a web-based version of the symptom tracker (ePRO); 4) to develop an enhanced training strategy for HNC patients; 5) to evaluate the usability of the ePRO; and 6) to assess the safety of omitting systematic lung imaging.

Purpose: For minimally invasive surgery of parathyroid adenomas, exact localization diagnostics are essential. Main imaging modalities used for diagnostics are sonography, SPECT with/without CT (traditional imaging) and 18F-choline-PET. The aim of our study was to identify predictors for inconclusive SPECT imaging and subsequently determine in which cases 18F-choline-PET is needed. Methods: Retrospective analysis of 138 patients with histologically confirmed primary hyperparathyroidism (pHPT). After sonography, patients underwent SPECT or SPECT/CT imaging, with subsequent 18F-choline-PET in cases of disconcordant results. Logistic regression analysis was used to identify clinical and laboratory factors predictive for negative SPECT results. Results: Sensitivity rates for sonography, SPECT, SPECT/CT, and choline-PET were 47 %, 49 %, 71.7 %, and 97 %, respectively. Logistic regression revealed lower PTH levels (p < 0.001), presence of structural thyroid disease (p = 0.018), and negative sonography (p < 0.001) as predictive of negative/equivocal SPECT outcome. An additional traditional imaging CT scan to a SPECT enhanced detection odds, as did greater adenoma weight. Urolithiasis, osteoporosis, and calcium values as measurement of activity and duration of disease showed no significant association with the detection rate. Furthermore, our study demonstrated that 18F-choline-PET exhibited remarkable sensitivity in detecting adenomas among patients with negative/equivocal SPECT results. Conclusion: Our study reveals potential predictive factors for a negative/equivocal SPECT outcome in pHPT. Identifying these factors might allow minimizing futile SPECT examinations and perhaps encourage timely utilization of 18F-choline-PET imaging. Our study reinforces the clinical significance of 18F-choline-PET, especially in complex cases with disconcordant results by conventional parathyroid imaging methods.

Background/Objectives: Molecular testing of thyroid nodules enables the detection of genetic alterations, which can help assess the risk of malignancy and tumor behavior. While telomerase reverse transcriptase (TERTp) mutations are known to be associated with aggressive disease, their exact prognostic significance when occurring alone or with other molecular alterations remains underreported. Methods: This study examined patients with thyroid cancer treated at two tertiary care hospitals from 2017 to 2024. We compared tumor behavior in patients with TERTp molecular alterations occurring alone and with concurrent molecular alterations. Aggressive histologic subtypes were defined as tall-cell, hobnail, and columnar variants of papillary carcinoma, as well as poorly differentiated and anaplastic carcinoma. High-risk disease was defined according to the 2015 ATA guidelines as gross extrathyroidal extension, lymph node metastasis >3 cm, postoperative elevated serum thyroglobulin, distant metastases, and/or positive resection margins. Statistical analysis was performed to assess differences between groups. Results: 30 patients with TERTp-positive thyroid malignancies were included. TERTp/BRAF V600E was the most prevalent mutation combination (n = 13, 43.3%), followed by TERTp alone (n = 8, 26.7%) and TERTp/RAS (n = 7, 23.4%). TERTp/EIF1AX/GNAS and TERTp/EIF1AX/PIK3CA were the least common combinations (n = 1, 3.3% each). Nodules with TERTp and concurrent mutations were significantly more likely to be classified as high-risk (p = 0.006) and were more frequently associated with aggressive histologic subtypes (p = 0.003) compared to those with TERTp mutations alone, which tended to exhibit more benign behavior. Conclusions: Thyroid carcinomas harboring both TERTp and concurrent molecular alterations are associated with more aggressive features and a higher likelihood of being classified as high-risk. In contrast, TERTp mutations occurring alone do not confer an elevated risk.

Background The aim of our study was to retrospectively analyze FDG PET/CT data in patients with facial nerve palsy (FNP) for the presence of the monocle sign. Patients and Methods A total of 85 patients with unilateral FNP were included into our study, thereof 73 with peripheral FNP and 12 with central FNP. FDG uptake (SUV max , SUV mean , total lesion glycolysis) was measured in both orbicularis oculi muscles (OOMs). FDG uptake of paretic and nonparetic muscles was compared in patients with FNP (Wilcoxon test and Mann-Whitney U test) and was also compared with FDG uptake in 33 patients without FNP (Mann-Whitney U test). SUV max ratios of OOM were compared. A receiver operating characteristic curve and Youden Index were used to determine the optimal cutoff SUV max ratio for the prevalence of contralateral peripheral FNP. Results The SUV max ratio of OOM was significantly higher in patients with peripheral FNP compared with patients with central FNP and those without FNP (1.70 ± 0.94 vs 1.16 ± 0.09 vs 1.18 ± 0.21, respectively; P < 0.001). The SUV max ratio of OOM yielded an area under the curve (AUC) of 0.719 (95% confidence interval, 0.630–0.809), with an optimal cutoff of 1.41, yielding a specificity of 94.4% and a sensitivity of 44.1% for identifying contralateral peripheral FNP. One hundred percent specificity is achieved using a cutoff of 1.91 (sensitivity, 29.4%). Conclusions Asymmetrically increased FDG uptake of the OOM (the “monocle sign”) indicates contralateral peripheral FNP. A nearly 2-fold higher SUV max represents a practically useful cutoff.

Background: Human papilloma virus (HPV) infection is an important risk factor in oropharyngeal cancer. Several studies have analyzed the association of tumoral HPV status and different imaging parameters in FDG-PET/CT and magnetic resonance (MR) diffusion-weighted imaging (DWI), with contradictory findings. In this retrospective study, the influence of HPV-status on different parameters in FDG-imaging and MR DWI is investigated. Methods: In this retrospective, single-center study we analyzed patients diagnosed with oropharyngeal cancer between January 2018 and December 2020 at a tertiary center in Switzerland. HPV status was assessed via p16 immunohistochemistry and/or PCR. Standardized uptake value (SUV), total lesion glycolysis (TLG) and apparent diffusion coefficient (ADC) were measured in pretreatment imaging (FDG-PET/CT, FDG-PET/MR, DWI MR). Statistical analysis was performed using Mann-Whitney-U tests. All p values reported are two-sided, and p values < 0.05 were considered statistically significant. Results: 142 patients were included. 67% of tumors were HPV-positive. Mean SUVmax in FDG-PET was 15.0+/-5.9 for HPV-positive tumors and 18.6+/-9.7 for HPV-negative tumors (p = 0.15). Mean ADC was 1109 x 106 mm2/s+/-326.8 for HPV-positive tumors and 1045.8 x 106 mm2/s+/-467.0 for HPV-negative tumors (p = 0.76). Conclusion: and Relevance: We found no correlation between oropharyngeal carcinoma HPV status and any of the analyzed imaging parameters.

Introduction Follow-up of head and neck squamous cell carcinoma (HNSCC) consists of regular clinical examinations and periodic imaging. Symptom monitoring is not integrated in current follow-up strategies. This study aims to assess 1) patients" readiness to periodically report symptoms, 2) feasibility of recruitment for a randomized trial integrating patient reported symptoms in follow-up, 3) user friendliness of a HNSCC-specific symptom questionnaire and 4) compliance with periodic symptom reporting.

Background In head and neck squamous cell carcinoma (HNSCC), salvage neck dissection (ND) is required after primary chemoradiation in case of residual nodal disease. Upon histopathological examination, viability of tumor cells is assessed but little is known about other prognostic histopathological features. In particular, the presence of swirled keratin debris and its prognostic value is controversial. The aim of this study is to examine histopathological parameters in ND specimens and correlate them with patient outcome to determine the relevant parameters for histopathological reporting. Materials and Methods Salvage ND specimen from a cohort of n = 75 HNSCC (oropharynx, larynx, hypopharynx) patients with prior (chemo) radiation were evaluated on H&E stains for the following parameters: viable tumor cells, necrosis, swirled keratin debris, foamy histiocytes, bleeding residues, fibrosis, elastosis, pyknotic cells, calcification, cholesterol crystals, multinucleated giant cells, perineural, and vascular invasion. Histological features were correlated with survival outcomes. Results Only the presence / amount (area) of viable tumor cells correlated with a worse clinical outcome (local and regional recurrence-free survival, (LRRFS), distant metastasis-free survival, disease-specific survival, and overall survival, p < 0.05) in both the univariable and multivariable analyses. Conclusion We could confirm the presence of viable tumor cells as a relevant negative prognostic factor after (chemo) radiation. The amount (area) of viable tumor cells further substratified patients with worse LRRFS. None of the other parameters correlated with a distinctive worse outcome. Importantly, the presence of (swirled) keratin debris alone should not be considered viable tumor cells (ypN0).

Although more common in females, thyroid cancer is deemed to be more aggressive in males. The reasons for sex disparities in thyroid cancer are not well understood. We hypothesised that differences in molecular mutations between females and males contribute to this phenomenon.

Importance:Oral cavity cancer often requires multidisciplinary management, subjecting patients to complex therapeutic trajectories. Prolonged treatment intervals in oral cavity cancer have been associated with poor oncological outcomes, but there has yet to be a study investigating treatment times in Canada. Objective:To report treatment delays for patients with oral cavity cancer in Canada and evaluate the outcomes of treatment delays on overall survival. Design, Setting, and Participants:This multicenter cohort study was performed at 8 Canadian academic centers from 2005 to 2019. Participants were patients with oral cavity cancer who underwent surgery and adjuvant radiation therapy. Analysis was performed in January 2023. Main Outcomes and Measures:Treatment intervals evaluated were surgery to initiation of postoperative radiation therapy interval (S-PORT) and radiation therapy interval (RTI). The exposure variables were prolonged intervals, respectively defined as index S-PORT greater than 42 days and RTI greater than 46 days. Patient demographics, Charlson Comorbidity Index, smoking status, alcohol status, and cancer staging were also considered. Univariate (log rank and Kaplan-Meier) and multivariate (Cox regression) analyses were performed to determine associations with overall survival (OS). Results:Overall, 1368 patients were included; median (IQR) age at diagnosis was 61 (54-70) years, and 896 (65%) were men. Median (IQR) S-PORT was 56 (46-68) days, with 1093 (80%) patients waiting greater than 42 days, and median (IQR) RTI was 43 (41-47) days, with 353 (26%) patients having treatment time interval greater than 46 days. There were variations in treatment time intervals between institutions for S-PORT (institution with longest vs shortest median S-PORT, 64 days vs 48 days; η2 = 0.023) and RTI (institution with longest vs shortest median RTI, 44 days vs 40 days; η2 = 0.022). Median follow-up was 34 months. The 3-year OS was 68%. In univariate analysis, patients with prolonged S-PORT had worse survival at 3 years (66% vs 77%; odds ratio 1.75; 95% CI, 1.27-2.42), whereas prolonged RTI (67% vs 69%; odds ratio 1.06; 95% CI, 0.81-1.38) was not associated with OS. Other factors associated with OS were age, Charlson Comorbidity Index, alcohol status, T category, N category, and institution. In the multivariate model, prolonged S-PORT remained independently associated with OS (hazard ratio, 1.39; 95% CI, 1.07-1.80). Conclusions and Relevance:In this multicenter cohort study of patients with oral cavity cancer requiring multimodal therapy, initiation of radiation therapy within 42 days from surgery was associated with improved survival. However, in Canada, only a minority completed S-PORT within the recommended time, whereas most had an appropriate RTI. An interinstitution variation existed in terms of treatment time intervals. Institutions should aim to identify reasons for delays in their respective centers, and efforts and resources should be directed toward achieving timely completion of S-PORT.

PET radiotracers that have the potential to raise the bar (26).