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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 < 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 < 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, 134:3170–3176, 2024 [ABSTRACT FROM AUTHOR]

Purpose: Early stage lip squamous cell carcinoma (lip SCC) can be treated with conventional excision, Mohs micrographic surgery (MMS), or brachytherapy. The aim of this retrospective study was to describe the medical outcomes, patient‐reported outcomes, and costs of these treatments. Methods: A retrospective cohort study of T1–T2 lip SSCs treated between 1996 and 2019. Medical outcomes, recurrences, and survival were retrieved from medical records. Facial appearance, facial function, and Quality of Life (QoL) were measured with the Face‐Q H&N and EQ‐5D‐5L questionnaires. Costs were also calculated. Results: Of the 336 lip SCCs, 122 were treated with excision, 139 with MMS, and 75 with brachytherapy. Locally, the recurrence rate was 2.7% and regionally 4.8%. There were 2% disease‐related deaths. T2‐stage and poor tumor differentiation were associated with recurrences. Posttreatment QoL, facial function, and appearance were rated as good. Brachytherapy was the most expensive treatment modality. Conclusion: Early‐stage lip SCC has a good prognosis, with a disease‐specific survival of 98.2% after a median follow‐up of 36 months, there was a high QoL and satisfaction at long‐term follow‐up. Based on the costs and the risk of locoregional recurrences, we believe that, for most noncomplex lip SCCs, MMS would be the most logical treatment option. [ABSTRACT FROM AUTHOR]

Graph Introduction In Western countries, approximately 11 % of patients with head and neck squamous cell carcinoma (HNSCC) develop a second primary tumor (SPT) [1]. Metachronous screening performed 1 year after synchronous screening resulted in the detection of one SPT (1/48; 2.1 %), while metachronous screening alone led to the detection of four SPTs in three patients (3/117; 2.6 %). 1 s b ), 10 patients with HNSCC had already been diagnosed with an esophageal SPT before these patients could be approached for endoscopic screening ( B Table 2 s b , patients 11-20). SPTs detected with endoscopic screening A total of 11 esophageal SPTs were detected in 10 /202 patients (5.0 %, 95 %CI 2.4 %-8.9 %) during 250 screening endoscopies (Table 2, patients 1-10). [Extracted from the article]

Patients with oral cavity cancer are almost always treated with surgery. The goal is to remove the tumor with a margin of more than 5 mm of surrounding healthy tissue. Unfortunately, this is only achieved in about 15% to 26% of cases. Intraoperative assessment of tumor resection margins (IOARM) can dramatically improve surgical results. However, current methods are laborious, subjective, and logistically demanding. This hinders broad adoption of IOARM, to the detriment of patients. Here we present the development and validation of a high-wavenumber Raman spectroscopic technology, for quick and objective intraoperative measurement of resection margins on fresh specimens. It employs a thin fiber-optic needle probe, which is inserted into the tissue, to measure the distance between a resection surface and the tumor. A tissue classification model was developed to discriminate oral cavity squamous cell carcinoma (OCSCC) from healthy oral tissue, with a sensitivity of 0.85 and a specificity of 0.92. The tissue classification model was then used to develop a margin length prediction model, showing a mean difference between margin length predicted by Raman spectroscopy and histopathology of −0.17 mm. [ABSTRACT FROM AUTHOR]

Simple Summary: The treatment outcomes in patients with head and neck cancer vary greatly, and serious side effects are often observed. Being able to predict therapy effects is therefore crucial for choosing the best treatment option for each patient. In this study, we developed an assay to evaluate how head and neck tumor cells respond to radiation and chemotherapy. Treatment of thin patient-derived cancer tissue slices in the laboratory (in vitro) resulted in large differences in individual tumor's reactions to treatment. In the sensitive tumors, cancer cells repaired the DNA damage inflicted by therapy only partially, stopped multiplying, and showed increased levels of cell death. On the other hand, resistant tumors were able to recover from the damage caused by the treatment. The next crucial step is to investigate whether the differences we observed in vitro can indeed predict the treatment outcomes; this is currently being tested in an ongoing clinical trial. Background: Head and neck squamous cell carcinoma (HNSCC) displays a large heterogeneity in treatment response, and consequently in patient prognosis. Despite extensive efforts, no clinically validated model is available to predict tumor response. Here we describe a functional test for predicting tumor response to radiation and chemotherapy on the level of the individual patient. Methods: Resection material of 17 primary HNSCC patients was cultured ex vivo, irradiated or cisplatin-treated, after which the effect on tumor cell vitality was analyzed several days after treatment. Results: Ionizing radiation (IR) affected tumor cell growth and viability with a clear dose-response relationship, and marked heterogeneity between tumors was observed. After a single dose of 5Gy, proliferation in IR-sensitive tumors dropped below 30% of the untreated level, while IR-resistant tumors maintained at least 60% of proliferation. IR-sensitive tumors showed on average a twofold increase in apoptosis, as well as an increased number and size of DNA damage foci after treatment. No differences in the homologous recombination (HR) proficiency between IR-sensitive and –resistant tumors were detected. Cisplatin caused a decrease in proliferation, as well as induction of apoptosis, again with marked variation between the samples. Conclusions: Our functional ex vivo assay discriminated between IR-sensitive and IR-resistant HNSCC tumors, and may also be suitable for predicting response to cisplatin. Its predictive value is currently under investigation in a prospective clinical study. [ABSTRACT FROM AUTHOR]

Post radiation mucosal ulcers (PRMU) after treatment for oropharyngeal squamous cell carcinoma (OPSCC) can have a huge negative impact on patients' quality of life, but little is known concerning risk factors and the impact of fraction size. Therefore, the goal of this study was to determine the pattern of PRMU development and to identify risk factors after a hypofractionated stereotactic body radiotherapy boost (SBRT) compared to conventionally fractionated radiotherapy for OPSCC. We performed a retrospective cohort study (N = 332) of OPSCC patients with ≥ 1-year disease-free survival, treated with 46 Gy Intensity Modulated Radiotherapy (IMRT) (2 Gy fractions) followed by either an SBRT boost of 16.5 Gy (5.5 Gy fractions) (N = 180), or 24 Gy IMRT (2 Gy fractions) (N = 152). PRMU (grade ≥ 2) was scored when observed > three months after the last radiotherapy (RT) fraction (CTCAE v5.0). Potential risk factors were analyzed with Cox regression models using death as competing risk. Dose at the PRMU site was calculated by projecting delineated PRMU on the planning CT. All cases of PRMU (N = 64) occurred within 24 months; all were grade 2. The cumulative incidence at 2 years in the SBRT boost group was 26% (N = 46) vs. 12% (N = 18) for conventional fractionation (p = 0.003). Most PRMU developed within nine months (N = 48). PRMU occurring > nine months (N = 16) were mainly observed in the SBRT boost group (N = 15). Sex (p = 0.048), acute tube feeding (p = < 0.001), tumor subsite tonsil (p = 0.001), and N stage (p = 0.017) were associated with PRMU risk at multivariable regression in the hypofractionated SBRT boost group. All 25 delineated PRMU were located within the high dose regions. The risk of PRMU should be included in the cost benefit analysis when considering future research using a hypofractionated SBRT boost for OPSCC patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Supposed risk of malignant transformation of salivary gland pleomorphic adenoma (SGPA) is an important reason for aggressive retreatment in recurrent pleomorphic adenoma (RPA). However, although the diagnostic category 'carcinoma ex‐pleomorphic adenoma' suggests that malignant transformation of a pleomorphic adenoma is a regular event, this has to date not been shown to occur in sequential lesions of one patient. Here, we show the molecular events in transformation to malignancy of a pleomorphic adenoma of the parotid gland. Detailed molecular analysis revealed an LIFR/PLAG1 translocation characteristic for pleomorphic adenoma and, next to this, a PIK3R1 frameshift mutation and several allelic imbalances. In subsequent malignant recurrences, the same LIFR/PLAG1 translocation, PIK3R1 frameshift mutation, and allelic imbalances were present in addition to TP53 mutations. Thus, this case not only shows malignant transformation of SGPA, but also demonstrates that molecular analysis can be of help in recognising malignancy in the rare instance of RPA. [ABSTRACT FROM AUTHOR]

Introduction: Achieving adequate resection margins during oral cancer surgery is important to improve patient prognosis. Surgeons have the delicate task of achieving an adequate resection and safeguarding satisfactory remaining function and acceptable physical appearance, while relying on visual inspection, palpation, and preoperative imaging. Intraoperative assessment of resection margins (IOARM) is a multidisciplinary effort, which can guide towards adequate resections. Different forms of IOARM are currently used, but it is unknown how accurate these methods are in predicting margin status. Therefore, this review aims to investigate: 1) the IOARM methods currently used during oral cancer surgery, 2) their performance, and 3) their clinical relevance. Methods: A literature search was performed in the following databases: Embase, Medline, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and Google Scholar (from inception to January 23, 2020). IOARM performance was assessed in terms of accuracy, sensitivity, and specificity in predicting margin status, and the reduction of inadequate margins. Clinical relevance (i.e., overall survival, local recurrence, regional recurrence, local recurrence-free survival, disease-specific survival, adjuvant therapy) was recorded if available. Results: Eighteen studies were included in the review, of which 10 for soft tissue and 8 for bone. For soft tissue, defect-driven IOARM-studies showed the average accuracy, sensitivity, and specificity of 90.9%, 47.6%, and 84.4%, and specimen-driven IOARM-studies showed, 91.5%, 68.4%, and 96.7%, respectively. For bone, specimen-driven IOARM-studies performed better than defect-driven, with an average accuracy, sensitivity, and specificity of 96.6%, 81.8%, and 98%, respectively. For both, soft tissue and bone, IOARM positively impacts patient outcome. Conclusion: IOARM improves margin-status, especially the specimen-driven IOARM has higher performance compared to defect-driven IOARM. However, this conclusion is limited by the low number of studies reporting performance results for defect-driven IOARM. The current methods suffer from inherent disadvantages, namely their subjective character and the fact that only a small part of the resection surface can be assessed in a short time span, causing sampling errors. Therefore, a solution should be sought in the field of objective techniques that can rapidly assess the whole resection surface. [ABSTRACT FROM AUTHOR]

Objective: The depth of invasion (DOI) is considered an independent risk factor for occult lymph node metastasis in oral cavity squamous cell carcinoma (OCSCC). It is used to decide whether an elective neck dissection (END) is indicated in the case of a clinically negative neck for early stage carcinoma (pT1/pT2). However, there is no consensus on the cut-off value of the DOI for performing an END. The aim of this study was to determine a cut-off value for clinical decision making on END, by assessing the association of the DOI and the risk of occult lymph node metastasis in early OCSCC. Methods: A retrospective cohort study was conducted at the Erasmus MC, University Medical Centre Rotterdam, The Netherlands. Patients surgically treated for pT1/pT2 OCSCC between 2006 and 2012 were included. For all cases, the DOI was measured according to the 8th edition of the American Joint Committee on Cancer guideline. Patient characteristics, tumor characteristics (pTN, differentiation grade, perineural invasion, and lymphovascular invasion), treatment modality (END or watchful waiting), and 5-year follow-up (local recurrence, regional recurrence, and distant metastasis) were obtained from patient files. Results: A total of 222 patients were included, 117 pT1 and 105 pT2. Occult lymph node metastasis was found in 39 of the 166 patients who received END. Univariate logistic regression analysis showed DOI to be a significant predictor for occult lymph node metastasis (odds ratio (OR) = 1.3 per mm DOI; 95% CI: 1.1–1.5, p = 0.001). At a DOI of 4.3 mm the risk of occult lymph node metastasis was >20% (all subsites combined). Conclusion: The DOI is a significant predictor for occult lymph node metastasis in early stage oral carcinoma. A NPV of 81% was found at a DOI cut-off value of 4 mm. Therefore, an END should be performed if the DOI is >4 mm. [ABSTRACT FROM AUTHOR]

Background: Inadequate resection margins in oral cavity squamous cell carcinoma have an adverse effect on patient outcome. Intraoperative assessment provides immediate feedback enabling the surgeon to achieve adequate resection margins. The goal of this study was to evaluate the value of specimen-driven intraoperative assessment by comparing the margin status in the period before and the period after the introduction of specimen-driven assessment as a standard of care (period 2010–2012 vs period 2013–2017). Methods: A cohort of patients surgically treated for oral squamous cell carcinoma at the Erasmus MC Cancer Institute, Rotterdam, between 2010–2012 was studied retrospectively and compared to results of a prospectively collected cohort between 2013–2017. The frequency, type and results of intraoperative assessment of resection margins were analyzed. Results: One hundred seventy-four patients were included from 2010–2012, 241 patients were included from 2013–2017. An increase in the frequency of specimen-driven assessment was seen between the two periods, from 5% in 2010–2012 to 34% in 2013–2017. When performing specimen-driven assessment, 16% tumor-positive resection margins were found in 2013–2017, compared to 43% tumor-positive resection margins overall in 2010–2012. We found a significant reduction of inadequate resection margins for specimen-driven intraoperative assessment (p < 0.001). Also, tumor recurrence significantly decreased, and disease-specific survival improved when performing specimen-driven intraoperative assessment. Conclusions: Specimen-driven intraoperative assessment improves resection margins and consequently, the outcome of oral cancer patients. We advocate this method as standard of care. [ABSTRACT FROM AUTHOR]

Background: Specimen‐driven intraoperative assessment of the resection margins provides immediate feedback if an additional excision is needed. However, relocation of an inadequate margin in the wound bed has shown to be difficult. The objective of this study is to assess a reliable method for accurate relocation of inadequate tumor resection margins in the wound bed after intraoperative assessment of the specimen. Methods: During oral cavity cancer surgery, the surgeon placed numbered tags on both sides of the resection line in a pair‐wise manner. After resection, one tag of each pair remained on the specimen and the other tag in the wound bed. Upon detection of an inadequate margin in the specimen, the tags were used to relocate this margin in the wound bed. Results: The method was applied during 80 resections for oral cavity cancer. In 31 resections an inadequate margin was detected, and based on the paired tagging an accurate additional resection was achieved. Conclusion: Paired tagging facilitates a reliable relocation of inadequate margins, enabling an accurate additional resection during the initial surgery. [ABSTRACT FROM AUTHOR]

Background/purpose: To determine the efficacy and toxicity profile of a stereotactic body radiotherapy (SBRT) boost as a first line treatment in patients with oropharyngeal squamous cell carcinoma (OPSCC). Materials and methods: We performed a retrospective cohort study in 195 consecutive OPSCC patients with T1-small T3 disease, treated at Erasmus MC between 2009 and 2016 with a SBRT (3 × 5.5 Gy) boost after 46 Gy IMRT. Primary endpoints were disease-specific survival (DSS) and Grade ≥3 toxicity (Common Terminology Criteria). The Kaplan-Meier method and Cox regression model were applied to determine rates and risk factors. Results: The median follow-up was 4.3 years. Treatment compliance was high (100%). Rates of 5-year DSS and late grade ≥3 toxicity were 85% and 28%, respectively. Five-year overall survival was 67%. The most frequently observed toxicities were mucosal ulceration or soft tissue necrosis (n = 30, 5 year 18%), dysphagia or weight loss (n = 18, 5 year 12%) and osteoradionecrosis (n = 11, 5 year 9%). Current smoker status (hazard ratio [HR] = 2.9, p =.001) and Charlson Comorbidity Index ≥2 (HR = 1.9, p =.03) were was associated with increased toxicity risk. Tooth extraction prior to RT was associated with increased osteoradionecrosis risk (HR = 6.4, p =.006). Conclusion: We reported on outcomes in the largest patient series to date treated with a hypofractionated boost for OPSCC. Efficacy was good with survival rates comparable to conventionally fractionated (chemo)radiotherapy. Grade ≥3 toxicity profiles showed high rates of soft tissue necrosis and osteoradionecrosis. Strategies to mitigate severe toxicity risks are under investigation to improve the tolerability of the SBRT boost. [ABSTRACT FROM AUTHOR]