Objectives
We characterize functional outcomes in head and neck cancer of unknown primary (CUP) based on primary site identification.
Methods
In this retrospective study, CUP cases were categorized ...as known primaries (KP) if a tumor was localized after diagnostic workup or persisting unknown primaries (UP). Age, sex, HPV status, diagnostic methods, and treatments regimens were collected. Pretreatment and short‐term posttreatment (3–6 months after completion of treatment) weights, PHQ‐9, Eating Assessment Tool (EAT‐10), and Voice Handicap Index (VHI‐10) scores were compared between UP and KP.
Results
Among 67 CUP patients, 35 (52.2%) had identified primaries (91.4% oropharyngeal and 8.6% nasopharyngeal). KP patients were younger (58 vs. 64, p = 0.04) and more likely to be HPV‐positive (88.6% vs. 50%, p = 0.002). Overall detection rates were 16.7% for PET/CT, 34.7% for direct laryngoscopy, and 46.6% for transoral robotic oropharyngectomy. Diagnostic workup was not significantly different between groups. Patients with KP received smaller intermediate radiation dose volumes (436.5 vs. 278.9 cc, p = 0.03) and lower doses to the cricopharyngeal muscle (41.6 vs. 24.6 Gy, p = 0.03).Pretreatment weights, PHQ‐9, EAT‐10, and VHI‐10 scores did not differ between groups. However, posttreatment, UP had greater relative weight loss (−14.1% vs. −7.6%, p = 0.032), higher EAT‐10 scores (12.5 vs. 3, p = 0.004), and higher PHQ‐9 scores (6 vs. 1.4, p = 0.017). Specifically, UP reported more stressful swallowing, difficulty swallowing solids and pills, and swallowing affecting public eating.
Conclusion
KP patients experienced less weight loss, depression, and reduced swallowing dysfunction, highlighting an early functional benefit of primary tumor identification likely driven by reduced radiation treatment volumes.
Level of Evidence
4 Laryngoscope, 134:701–707, 2024
Squamous cell carcinoma (SCC) from an unknown primary tumor (SCCUP) accounts for 2.0%–5.0% of all head and neck cancers. SCCUP presents as enlarged cervical lymph nodes without evidence of a primary ...tumor upon physical examination. Primary site detection is important to target treatment and avoid treatment-related morbidity. In this review, we discuss updates in SCCUP management. Diagnostic workup should focus on localization of the primary tumor in SCCUP. Initial workup centers on neck biopsy to confirm the presence of SCC. Given the increasing incidence of HPV-related SCC in the oropharynx, HPV testing is crucial. An HPV-positive status can localize the tumor to the oropharynx, a common site for occult tumors. Imaging includes neck CT and/or MRI, and PET/CT. After imaging, panendoscopy, palatine tonsillectomy or diagnostic transoral robotic surgery can facilitate high rates of primary tumor localization. Primary tumor localization influences treatments administered. SCCUP has traditionally been treated aggressively with large treatment fields to all potential disease sites, which can induce weight loss and swallowing dysfunction. As a result, primary localization can reduce radiation fields and provide possible de-escalation to primary surgical management. Advances in intensity-modulated radiation therapy and dose management also have the potential to improve functional outcomes in SCCUP patients. Given the improved prognosis associated with HPV-positive SCCs, HPV tumor status may also inform future treatment de-intensification to reduce treatment-related toxicity.
We analysed the outcomes of 726 cases of primary head and neck cancer patients managed between 1996 and 2008, including those managed in the multidisciplinary clinic or team setting (MDT) and those ...managed outside of an MDT by individual disciplines (non-MDT) in the same institution.
Data were collected from the Hospital Based Cancer Registry and a database within the Head and Neck Cancer Clinic. Univariable comparisons and multivariable analyses were performed using a logistic regression model. Survival by staging was analysed. Comparisons of management and outcomes were made between MDT and non-MDT patients.
395 patients (54%) had been managed in the MDT vs 331 patients (46%) non-MDT. MDT patients were more likely to have advanced disease (likelihood ratio χ(2)=44.7, P<0.001). Stage IV MDT patients had significantly improved 5-year survival compared with non-MDT patients (hazard ratio=0.69, 95% CI=0.51-0.88, P=0.004) and more synchronous chemotherapy and radiotherapy (P=0.004), and the non-MDT group had more radiotherapy as a single modality (P=0.002).
The improved survival of MDT-managed stage IV patients probably represents both the selection of multimodality treatment and chemotherapeutic advances that these patients received in a multidisciplinary team setting by head and neck cancer specialists as opposed to cancer generalists in a non-MDT setting.
Patients presenting with head and neck squamous cell carcinoma of unknown primary (HNSCCUP) remain challenging clinical scenarios as large variation exists in practices used to locate the primary.
...The objective of this systematic review is to review of the literature and offer recommendations for oropharyngeal biopsies in HNSCCUP.
Pubmed, Medline and Embase were searched to identify studies from inception to October 2021. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed.
A total of 483 articles were included and screened, 41 studies met the inclusion criteria, including over 3400 patients from the original articles (122 of these patients were reported on in two sequential articles by a single author - table 1) and 4 large metaanalyses including 1852 patients. The primary site identification rate following random biopsies or deep tissue biopsies is less than 5% in most studies. The mean detection rate following ipsilateral tonsillectomy is 34%; two pooled analyses indicate that the mean detection rate following tongue base mucosectomy is 64%, with this figure rising when the tonsils are negative.
High level evidence is lacking, with heterogeneity in the reported studies. Published meta-analyses are based on retrospective data. There is little evidence supporting the practice of random/non-directed oropharyngeal biopsies. Available evidence supports palatine tonsillectomy and tongue base mucosectomy compared to deep tissue biopsies.
Aspartate β-hydroxylase (ASPH) is a protein associated with malignancy in a wide range of tumors. We hypothesize that inhibition of ASPH activity could have anti-tumor properties in patients with ...head and neck cancer. In this study, we screened tumor tissues of 155 head and neck squamous cell carcinoma (HNSCC) patients for the expression of ASPH using immunohistochemistry. We used an ASPH inhibitor, MO-I-1151, known to inhibit the catalytic activity of ASPH in the endoplasmic reticulum, to show its inhibitory effect on the migration of SCC35 head and neck cancer cells in cell monolayers and in matrix-embedded spheroid co-cultures with primary cancer-associated fibroblast (CAF) CAF 61137 of head and neck origin. We also studied a combined effect of MO-I-1151 and HfFucCS, an inhibitor of invasion-blocking heparan 6-O-endosulfatase activity. We found ASPH was upregulated in HNSCC tumors compared to the adjacent normal tissues. ASPH was uniformly high in expression, irrespective of tumor stage. High expression of ASPH in tumors led us to consider it as a therapeutic target in cell line models. ASPH inhibitor MO-I-1151 had significant effects on reducing migration and invasion of head and neck cancer cells, both in monolayers and matrix-embedded spheroids. The combination of the two enzyme inhibitors showed an additive effect on restricting invasion in the HNSCC cell monolayers and in the CAF-containing co-culture spheroids. We identify ASPH as an abundant protein in HNSCC tumors. Targeting ASPH with inhibitor MO-I-1151 effectively reduces CAF-mediated cellular invasion in cancer cell models. We propose that the additive effect of MO-I-1151 with HfFucCS, an inhibitor of heparan 6-O-endosulfatases, on HNSCC cells could improve interventions and needs to be further explored.
Objectives
To investigate the effect of chemotherapy versus no chemotherapy on the risk of second primary head and neck malignancies (SPHNMs) in patients with locally advanced oral squamous cell ...carcinoma (OSCC) and to assess the survival outcomes of patients with SPHNM.
Materials and methods
A total of 937 OSCC patients were divided into chemotherapy and nonchemotherapy groups by propensity score matching (PSM). In the presence of the competing event of non-SPHNM death, the fine and gray modified Cox proportional hazard model was fitted to detect the impact of various factors, including the history of chemotherapy, on SPHNM risk. The Kaplan–Meier method was used to assess the survival outcomes of patients.
Results
After PSM, the 10-year cumulative probability of SPHNM was 10.7% for patients who received chemotherapy and 22.1% for patients who did not. The fine and gray regression model showed that prior chemotherapy was associated with a 51% reduced risk of SPHNM (adjusted subdistribution hazard ratio (sHR): 0.49, 95% confidence interval (
CI
): 0.29–0.84,
P
= 0.1). The disease-free survival (DFS) rates did not differ significantly between the SPHNM and non-SPHNM groups. And there were no significant differences in DFS rates between the patients with and those without prior chemotherapy in the SPHNM group.
Conclusions
Chemotherapy for locally advanced primary OSCC is associated with a decreased incidence of subsequent SPHNM. However, chemotherapy for the primary cancer does not improve DFS in patients with SPHNM.
Clinical relevance
Chemotherapy plays a positive role in preventing SPHNMs for patients with oral squamous cell carcinoma.
Clinical trial registration
Before January 2015, the data were retrieved retrospectively, while after January 2015, the data were collected prospectively in a POROMS database (ClinicalTrials.gov ID: NCT02395367).
Percutaneous endoscopic gastrostomy (PEG) is a relatively safe procedure that represents an important supportive adjunctive component for patients with primary head and neck squamous cell carcinoma ...(HNSCC). The HNSCC population is considered a high-risk group for developing critical nutritional deficiency due to a multitude of factors. Nevertheless, as the use of PEG in modern practice is gaining more popularity due to various indications, unusual complications have been increasingly reported. PEG site metastasis from primary HNSCC has emerged as a rare, yet serious oncological phenomenon that warrants careful consideration. The authors report an unusual case of squamous cell carcinoma (SCC) of the hypopharynx that metastasized to the gastric body mucosa through a PEG site. The metastatic SCC presented as massive gastrointestinal bleeding, and esophagogastroscopy revealed an ulcerated mass in the gastric body masquerading as a primary gastric adenocarcinoma. Histopathology and immunohistochemistry examination confirmed metastatic SCC which concurred with the patient’s primary hypopharyngeal SCC. The review of the updated literature revealed that a total of 121 cases of this rare oncological entity have been reported to date. Physicians need to be vigilant of the symptoms of PEG site metastasis to accurately diagnose and manage the care of this rare occurrence as it is associated with poor prognosis.
Opinion statement
Recurrent and second primary head and neck cancers represent a clinical challenge due to frequently unresectable and/or locally advanced disease. Given that many of these patients ...have received definitive doses of radiation previously, reirradiation is associated with significant morbidity. Use of modern approaches such as conformal photon-based planning and charged particle therapy using protons or carbon ions allows for greater sparing of normal tissues while maintaining or escalating doses to tumor volumes. While the reirradiation data has consistently shown benefits to local control and even survival from escalation of radiotherapy dose, excessive cumulative doses can result in severe toxicities, including fatal carotid blowout syndrome. For all modalities, appropriate patient selection is of utmost importance. Large-scale trials and multi-institutional registry data are needed to standardize treatment modalities, and to determine optimal doses and volumes for reirradiation.
Purpose
To evaluate the prognostic utility of nodal metabolic parameters derived from FDG PET/CT performed before radiotherapy (prePET) and during the third week of radiotherapy (iPET) in patients ...with mucosal primary head and neck squamous cell carcinoma (MPHNSCC).
Methods
This analysis included 75 patients with newly diagnosed locally advanced node-positive MPHNSCC treated with radical radiotherapy and concurrent systemic therapy who underwent prePET and iPET: N1 11 patients, N2a 38, N2b 12, N2c 9, N3 5. The median follow-up was 28 months (9 – 70 months). The maximum and mean standardized uptake values (SUVmax and SUVmean), metabolic tumour volume (MTV) and total lesional glycolysis (TLG) of the index lymph node (node with the highest TLG) and the combined total lymph nodes, and their percentage reductions on iPET were determined, and the results were correlated with 3-year Kaplan-Meier locoregional, regional and distant metastatic failure-free survival (FFS), disease-free survival (DFS) and overall survival (OS). Optimal cut-off values were derived from receiver operating characteristic curves. Cox regression univariate and multivariate analyses with clinical covariates were performed.
Results
Based on assessment of residual nodal metabolic burden during treatment, the iPET index node SUVmean (optimal cut-off value 2.95 g/ml) and the total node SUVmean (optimal cut-off value 3.25) were the best independent predictors of outcome in the multivariate analysis: index node SUVmean for DFS and OS
p
= 0.033 and 0.003, respectively, and the total node SUVmean for locoregional FFS, DFS and OS
p
= 0.028, 0.025 and 0.014, respectively. Based on the assessment of response rates during treatment, a reduction of more than 50 % in the total node TLG was the best biomarker for locoregional and regional FFS, DFS and OS in the multivariate analysis (
p
= 0.001, 0.016, 0.001 and 0.004, respectively), and reduction in the total node MTV for locoregional FFS, DFS and OS (
p
= 0.026, 0.003 and 0.014, respectively). There were no significant correlations between oncological outcomes and prePET nodal parameters.
Conclusion
We demonstrated that the index node and total node SUVmean on iPET and a reduction of more than 50 % in MTV and TLG are useful imaging biomarkers, and can potentially identify those patients with MPHNSCC who have a high risk of locoregional metastatic failure and death.
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