Quality of Life of Oligometastatic and Polymetastatic Head and Neck Squamous Cell Carcinoma Patients

Objective: Evidence suggests that distant metastasis in head and neck squamous cell carcinoma is a spectrum of disease. Previous studies show that oligometastasis has favorable survival compared with polymetastasis. The quality of life of patients with oligometastasis remains unknown. To further solidify the position of oligometastasis as a separate entity, we hypothesized that oligometastatic patients experience better quality of life than polymetastatic patients.Methods: Patients with distant metastasis were stratified into three groups: oligometastasis (≤3 metastatic foci in ≤2 anatomic sites), explosive metastasis (≥4 metastatic foci at one anatomic site), and explosive-disseminating metastasis (spread to ≥3 anatomic sites). Quality of life was assessed every 2 months post distant metastasis diagnosis. Results: Between January 1, 2016, and December 31, 2021, a total of 161 patients with distant metastasis were identified, with a total of 397 measurements. In this group, 57 (35.4%) patients had oligometastasis, 35 (21.7%) patients had explosive metastasis, and 69 (42.9%) patients had explosive-disseminating metastasis. Their median post-distant metastasis survivals were 8.5 months, 3.2 months, and 3.2 months respectively (p &lt; 0.001). A significantly better overall quality of life was observed in the oligometastasis group compared with the polymetastatic groups (+0.75 out of 7, p &lt; 0.05). Furthermore, oligometastatic patients performed better in the subdomains of “physical functioning,” “fatigue,” and “pain.”. Conclusion: Results from this study underscore that subgroups exist regarding quality of life and survival within distant metastasis, with polymetastatic patients performing worse than oligometastatic patients. This highlights the significance of tailored interventions that consider the unique challenges faced by each metastatic group of patients. Level of Evidence: 3, retrospective cohort study Laryngoscope, 2024.</p

Validation of the prognostic model “oncologiq palliative” for head and neck cancer patients

Purpose: Patients diagnosed with incurable head and neck squamous cell carcinoma (HNSCC) have a poor prognosis, with a median survival of approximately five months. Physicians often struggle to predict prognosis accurately and tend to overestimate survival. Timely sharing of validated accurate individual information on life expectancy could aid in facilitating better patient counseling. However, this knowledge is lacking. Therefore, the aim of this study is to conduct temporal and external validation of the prognostic model OncologIQ Palliative to assess its accuracy and generalizability. Methods: The validation procedure involved temporal assessment in a retrospective cohort of 355 palliative HNSCC patients from Erasmus MC (2017–2020), followed by external validation in a retrospective cohort of 44 patients from Leiden University Medical Center (2019–2021).The discriminative ability of OncologIQ Palliative was assessed using the C-index and calibration was evaluated through graphical assessment, intercept, and slope. Results: The temporal cohort had a median follow-up of 115 days, and the external cohort 143 days. The model showed moderate discriminative ability in temporal validation (C-index 0.66) and better discrimination in external validation (C-index 0.71). Reasonable agreement was observed between predicted and observed 6-month and 1-year survival rates, with some deviations from the perfect calibration line. Conclusion: The validation methods conducted in this study underscored the reliability of OncologIQ Palliative. They showed adequate calibration and discrimination in both validation procedures, thereby facilitating the provision of more accurate prognostic counselling for head and neck cancer patients in the palliative phase.</p

A New Proposal for Adequate Resection Margins in Larynx and Hypopharynx Tumor Surgery—:Are the RCP Guidelines Feasible?

Background: Resection margins are an important prognostic factor for patients with head and neck cancer. In general, for head and neck surgery, a margin &gt;5 mm is advised by the Royal College of Pathologists. However, this cannot always be achieved during laryngeal and hypopharyngeal surgery. The aim of this study is to identify the resection surfaces and measure the maximum feasible margins per subsite. The clinical relevance of these maximum feasible resection margins were analyzed in this descriptive anatomical study. Methods: head and neck surgeons and a pathologist from the Erasmus MC performed a total laryngectomy and laryngopharyngectomy on a head and neck specimen specifically available for research. Results: For a total laryngectomy, resection margins &gt;5 mm were not feasible for the ventral and dorsal resection surface. For a total laryngopharyngectomy, resection margins &gt;5 mm were not feasible for the ventral, dorsal and lateral resection surface. Conclusion: Clear resection margins, defined as a margin &gt;5 mm, are not always feasible in laryngeal and hypopharyngeal surgery, due to the anatomy of the larynx and tumor location. However, striving for a maximum feasible margin is still the main goal. We propose a new guideline for maximum feasible but adequate resection margins in larynx and hypopharynx tumor surgery.</p

Detecting head and neck lymph node metastases with white light reflectance spectroscopy; a pilot study

Introduction: A challenge in the treatment of patients with head and neck cancer is the management of occult cervical lymph node (LN) metastases. Single-fiber reflectance (SFR) spectroscopy has the potential to detect physiological tissue changes that occur in a positive LN. This pilot study aimed to investigate whether SFR spectroscopy could serve as an alternative or additional technique to detect cervical lymph node metastases. Materials and Methods: We performed intraoperative SFR spectroscopy measurements of LNs with and without malignancies. We analyzed if physiological and scattering parameters were significantly altered in positive LNs. Results: Nine patients with a total of nineteen LNs were included. Three parameters, blood volume fraction (BVF), microvascular saturation (StO2), and Rayleigh amplitude, were significantly lower in positive LNs. They were combined into one optical parameter ‘delta’, using discriminant analysis. Delta was significantly decreased in positive LNs, p = 0,0006. It had a high diagnostic accuracy where the sensitivity, specificity, PPV, and NPV were 90,0%, 88.9%, 90,0%, and 88.9%, respectively. The area under the ROC curve was 96.7% (95% confidence interval 89.7–100.0%). Conclusion: This proof of principle study is a first step in the development of an SFR spectroscopy technique to detect LN metastases in real time. A next step towards this goal is replicating these results in LNs with smaller metastases and in a larger cohort of patients. This future study will combine SFR spectroscopy with fine-needle aspiration, using the same needle, to perform preoperative in vivo measurements.</p

Clinical Relevance of Resection Margins in Patients with Total Laryngectomy or Laryngopharyngectomy

Background: Laryngeal and hypopharyngeal cancer is complex and resection margins are therefore constrained. The aim of this study was to investigate the clinical relevance of resection margins in laryngeal and hypopharyngeal surgery. Methods: A retrospective cohort study was performed for patients treated with a total laryngectomy (TL) or laryngopharyngectomy (TLP) for laryngeal or hypopharyngeal squamous cell carcinoma (LSCC and HSCC, respectively). Within the groups primary LSCC, recurrent LSCC, primary HSCC, and recurrent HSCC the relationship between the status of the resection margin according to the Royal Collage of Pathology and the recurrence and survival rates were investigated. Results: Positive resection margins were found in 54% for primary LSCC, 29% for recurrent LSCC, 62% for primary HSCC, and 44% for recurrent HSCC. For primary and recurrent LSCC, there was a linear association between total recurrence and narrowing margins (p = 0.007 resp. p = 0.008). Multivariate survival analysis for primary and recurrent LSCC showed a significantly worse disease free and disease-specific survival in case of positive margins compared to clear margins. Conclusion: Similar survival rates were recorded for close and clear margins for primary and recurrent LSCC. This may suggest that a margin &gt; 5 mm is not clinically relevant in terms of survival. Therefore, a margin of 1–5 mm should be accepted in certain subsites. Margins &lt; 1 mm are related to significantly worse outcomes and should be avoided.</p

Treatment of head and neck carcinoma of unknown primary:Cracking a nut with a sledgehammer?

Objectives: To compare the impact on survival and late radiation toxicity of patients with squamous cell carcinoma of unknown primary who were treated with ipsilateral neck dissection and ipsilateral postoperative radiotherapy (PORT) and patients treated with ipsilateral neck dissection and PORT to both sides of the neck plus the pharyngeal axis. Methods: Retrospective cohort study performed at the Erasmus University Medical Center in which 78 patients with squamous cell carcinoma of unknown primary were identified. Thirty-nine patients received PORT to both sides of the neck plus the pharyngeal axis (BILAX) and another 39 patients were irradiated on the ipsilateral neck (IPSI) only. The endpoints of the present study were 3-year overall survival (OS), 3-year disease-free survival (DFS), and overall late radiation toxicity. Results: The 3-year OS rate of the entire group of 78 patients was 74.2% and the 3-year DFS rate was 72.7%. The 3-year OS rates for the IPSI and the BILAX groups were 74.4% and 74.1%, respectively (P =.654). The most common late radiation toxicity experienced was xerostomia (64.8%), which was significantly more often seen in the BILAX group than in the IPSI group (83.8% and 44.1%, respectively, P =.001). Overall late radiation toxicity was significantly higher in the BILAX group (P =.003). Conclusion: There was no significant difference in OS and DFS rates between the IPSI and the BILAX group. Late radiation toxicity was significantly higher in the BILAX group. Level of Evidence: Level 2b: Individual retrospective cohort study.</p

The Potential of MET Immunoreactivity for Prediction of Lymph Node Metastasis in Early Oral Tongue Squamous Cell Carcinoma

Objective MET positivity is independently associated with survival in oral squamous cell carcinoma (OSCC). Since MET is a known orchestrator of invasive tumor growth, we investigated its association with LNM in early oral tongue squamous cell carcinoma (OTSCC). As it is recommended by the NCCN to use tumor depth of invasion (DOI) in making decisions on elective neck dissection (END), the results obtained for MET positivity were aligned with those for DOI > 4 mm. The cutoff value used in our institution. Methods Tumor samples from patients who underwent primary tumor resection and neck dissection between 1995 and 2013, were collected from the archives of the Leiden and Erasmus University Medical Center. Immunohistochemistry with D1C2 was performed to identify MET negative (= 10% uniform positivity) cancers. ROC curve analysis and the Chi-squared test were used to investigate the association of MET positivity with LNM (pN+ and occult). Binary logistic regression was used to investigate the association of MET positivity with LNM. Results Forty-five (44.1%) of the 102 cancers were MET positive. Ninety were cN0 of which 20 were pN+ (occult metastasis). The remaining 12 cancers were cN+, of which 10 were proven pN+ and 2 were pN0. MET positivity was associated with LNM with a positive predictive value (PPV) of 44.4% and a negative predictive value (NPV) of 82.5% for pN+. For the occult group, the PPV was 36.8% and the NPV was 88.5%. Regression analysis showed that MET positivity is associated with pN+ and occult LNM (p-value < 0.05). Conclusion MET positivity is significantly associated with LNM in early OTSCC, outperforming DOI. The added value of MET positivity could be in the preoperative setting when END is being considered during the initial surgery. For cases with DO

A comprehensive approach to defining the cutoff value of oligometastasis in head and neck squamous cell carcinoma

Background: Patients with limited distant metastatic disease, also known as oligometastasis, show better survival rates than polymetastatic patients, and may be amenable for curative-intent treatment. The definition of oligometastasis, however, is unknown, and no quantitative analyses on the cutoff value for oligometastasis have been performed before. This study aims to derive specific threshold values for the number of metastases and affected locations that defines oligometastatic disease in head and neck squamous cell carcinoma. Methods: A retrospective cohort study was conducted including all patients diagnosed with distant metastases between 2006 and 2021. For each patient, the number of distant metastases and affected locations was recorded on the basis of the available imaging at the time of diagnosis. Cox regression analyses and a machine-learning k-means algorithm were used to determine threshold values. Results: A total of 384 patients untreated for their metastatic foci were analyzed. Most patients (n = 207; 53.9%) had metastasis to one anatomic location, followed by metastases in two anatomic locations (n = 62; 16.1%). The majority of patients had ≥9 metastatic foci (n = 174; 45.3%), followed by one focus (n = 74; 19.3%) and two foci (n = 32; 8.3%). Cox regression and machine-learning k-means models showed that although the number of metastases did not predict survival, the number of affected locations did significantly (p &lt;.001), by identifying a threshold of two locations. Conclusions: Contrary to the prevalent dogma, the definition of oligometastasis should not be defined by the number of metastases but rather by the number of affected locations, with a maximum number of affected locations set at two.</p

Rotterdam Oncology Documentation (RONCDOC) - a high-quality data warehouse and tissue collection for head and neck cancer

BACKGROUND: Every year, almost 900.000 people are diagnosed with head and neck cancer (HNC) worldwide. HNC contains many different subsites and a large variability in tumor biology. This often results in small and/or heterogeneous study populations. Developing overarching databases is an efficient solution to collect and analyze data of these smaller subsets of patients and to facilitate data sharing among research groups. The few existing large databases often include only basic characteristics. In addition, hospital-based cohorts that include more variables are often not collected consecutively, resulting in selection bias. Therefore, we established a hospital-based cancer registry system "Rotterdam Oncology Documentation" (RONCDOC), a complete and consecutive data warehouse and tissue collection for HNC, directly registered at the source. The primary aim of this paper is to report on our data collection protocol in order to make the RONCDOC data accessible and reusable for other researchers, and to offer a blue print to other consortia planning to establish their own data warehouse. METHODS: Data collected in the Netherlands Cancer Registry (NCR) of patients with HNC were obtained from the Netherlands comprehensive cancer organization (IKNL) and merged with corresponding data from the electronic patient file (EPF). The data were manually verified using the EPF, and enriched with additional variables from the EPF according to an extensive data entry protocol. Furthermore, a comprehensive validation protocol was developed to guarantee the quality of the data. Tissue microarrays (TMAs) were constructed from resection specimens of patients with primary oral squamous cell carcinoma. CONCLUSION: With RONCDOC, we have established a consecutive and high-quality data warehouse for HNC. This paper outlines the essential steps for establishing such a data warehouse, offering a blueprint for other consortia. TRIAL REGISTRATION: This study was approved by the ethics committee of the Erasmus Medical Center (MEC-2016-751).</p

Screening for synchronous esophageal second primary tumors in patients with head and neck cancer

Patients with head and neck squamous cell carcinoma (HNSCC) have an increased risk of developing esophageal second primary tumors (ESPTs). We aimed to determine the incidence, stage, and outcome of synchronous ESPTs in patients with HNSCC in a Western population. We performed a prospective, observational, and cohort study. Patients diagnosed with HNSCC in the oropharynx, hypopharynx, any other sub-location in combination with alcohol abuse, or patients with two synchronous HNSCCs, between February 2019 and February 2020 underwent screening esophagogastroduodenoscopy (EGD). ESPT was defined as presence of esophageal squamous cell carcinoma (ESCC) or high grade dysplasia (HGD). Eighty-five patients were included. A lesion suspected for ESPT was detected in 14 of 85 patients, which was pathologically confirmed in five patients (1 ESCC and 4 HGD). The radiotherapy field was extended to the esophagus in two of five patients, HGD was treated with endoscopic resection in three of five patients. None of the ESPTs were detected on MRI and/or CT-scan prior to EGD. Of the remaining nine patients, three had low grade dysplasia on histology whereas the other six patients had benign lesions. Incidence of synchronous ESPT was 5.9% in our cohort of HNSCC patients. All ESPTs were diagnosed at an early stage and treated with curative intent. We recommend that screening for synchronous ESPTs should be considered in a selected group of patients with HNSCC