BackgroundElective neck irradiation (ENI) is performed in head and neck cancer patients treated with definitive (chemo)radiotherapy. The aim is to eradicate nodal metastases that are not detectable... Show moreBackgroundElective neck irradiation (ENI) is performed in head and neck cancer patients treated with definitive (chemo)radiotherapy. The aim is to eradicate nodal metastases that are not detectable by pretreatment imaging techniques. It is conceivable that personalized neck irradiation can be performed guided by the results of sentinel lymph node biopsy (SLNB). It is expected that ENI can be omitted to one or both sides of the neck in 9 out of 10 patients, resulting in less radiation side effects with better quality of life.Methods/designThis is a multicenter randomized controlled trial aiming to compare safety and efficacy of treatment with SLNB guided neck irradiation versus standard bilateral ENI in 242 patients with cN0 squamous cell carcinoma of the oropharynx, larynx or hypopharynx for whom bilateral ENI is indicated. Patients randomized to the experimental-arm will undergo SLNB. Based on the histopathologic status of the SLNs, patients will receive no ENI (if all SLNs are negative), unilateral neck irradiation only (if a SLN is positive at one side of the neck) or bilateral neck irradiation (if SLNs are positive at both sides of the neck). Patients randomized to the control arm will not undergo SLNB but will receive standard bilateral ENI. The primary safety endpoint is the number of patients with recurrence in regional lymph nodes within 2 years after treatment. The primary efficacy endpoint is patient reported xerostomia-related quality of life at 6 months after treatment.DiscussionIf this trial demonstrates that the experimental treatment is non-inferior to the standard treatment in terms of regional recurrence and is superior in terms of xerostomia-related quality of life, this will become the new standard of care. Show less
In't Veld, S.G.J.G.; Arkani, M.; Post, E.; Antunes-Ferreira, M.; D'Ambrosi, S.; Vessies, D.C.L.; ... ; Wurdinger, T. 2022
Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising... Show moreCancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I-IV cancer patients and in half of 352 stage I-III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening. Show less
Background: T4-classified squamous cell carcinoma (SCC) of external auditory canal (EAC) can potentially involve different anatomical structures, which could translate into different treatment... Show moreBackground: T4-classified squamous cell carcinoma (SCC) of external auditory canal (EAC) can potentially involve different anatomical structures, which could translate into different treatment strategies and survival outcomes within one classification. Our aim is to evaluate the clinical added value of T4-subclasses proposed by Lavieille and by Zanoletti. Methods: Retrospective data, including patients with primary operated cT4-classified EAC SCC, was obtained from 12 international hospitals. We subclassified according to the T4-subclasses. The treatment strategies, disease-free survival (DFS) and overall survival per subclass were calculated. Results: A total of 130 T4-classified EAC SCC were included. We found commonly used treatment strategies per subclass according to Lavieille and the DFS seems also to differ per subclass. Subclass according to Zanoletti showed comparable treatment strategies and survival outcomes per subclass. Conclusion: Our study suggests that the subclass according Lavieille might have added value in clinical practice to improve care of T4-classified EAC SCC. Show less
Background: Inevitably, the emergence of COVID-19 has impacted non-COVID care. Because timely diagnosis and treatment are essential, especially for patients with head and neck cancer (HNC) with... Show moreBackground: Inevitably, the emergence of COVID-19 has impacted non-COVID care. Because timely diagnosis and treatment are essential, especially for patients with head and neck cancer (HNC) with fast-growing tumours in a functionally and aesthetically important area, we wished to quantify the impact of the COVID-19 pandemic on HNC care in the Netherlands.Material and Methods: This population-based study covered all, in total 8468, newly diagnosed primary HNC cases in the Netherlands in 2018, 2019 and 2020. We compared incidence, patient and tumour characteristics, primary treatment characteristics, and time-to-treatment in the first COVID-19 year 2020 with corresponding periods in 2018 and 2019 (i.e. pre-COVID).Results: The incidence of HNC was nearly 25% less during the first wave (n = 433) than in 2019 (n = 595) and 2018 (n = 598). In April and May 2020, the incidence of oral cavity and laryngeal carcinomas was significantly lower than in pre-COVID years. There were no shifts in tumour stage or alterations in initial treatment modalities.Regardless of the first treatment modality and specific period, the median number of days between first visit to a HNC centre and start of treatment was significantly shorter during the COVID-19 year (26-28 days) than pre-COVID (31-32 days, p < 0.001).Conclusion: The incidence of HNC during the Netherlands' first COVID-19 wave was significantly lower than expected. The expected increase in incidence during the remainder of 2020 was not observed. Despite the overloaded healthcare system, the standard treatment for HNC patients could be delivered within a shorter time interval. (C) 2021 The Author(s). Published by Elsevier B.V. Show less
Human papilloma virus (HPV) is a well-established causative factor in a subset of squamous cell carcinomas of the head and neck (HNSCC). Although HPV can be detected in various anatomical subsites,... Show moreHuman papilloma virus (HPV) is a well-established causative factor in a subset of squamous cell carcinomas of the head and neck (HNSCC). Although HPV can be detected in various anatomical subsites, HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) is the most common HPV-related malignancy of the head and neck, and its worldwide incidence is constantly rising. Patients with OPSCC are generally younger, have less co-morbidities and generally have better prognosis due to different biological mechanisms of carcinogenesis. These facts have generated hypotheses on potential treatment modifications, aiming to minimize treatmentrelated toxicities without compromising therapy efficacy. Numerous randomized clinical trials have been designed to verify this strategy and increasingly realworld evidence data from retrospective, observational studies is becoming available. Until now, the data do not support any modification in contemporary treatment protocols. In this narrative review, we outline recent data provided by both randomized controlled trials and real-world evidence of HPV-positive OPSCC in terms of clinical value. We critically analyze the potential value and drawbacks of the available data and highlight future research directions.This article was written by members and invitees of the International Head and Neck Scientific Group. (www.IHNSG.com) Show less
Nonsurgical primary treatment of early and advanced laryngeal squamous cell carcinoma, employing radiotherapy with or without chemotherapy, is considered a standard of care in many centers... Show moreNonsurgical primary treatment of early and advanced laryngeal squamous cell carcinoma, employing radiotherapy with or without chemotherapy, is considered a standard of care in many centers throughout the world. When patients have persistent or recurrent disease after non-surgical treatment, salvage surgery is frequently the only remaining potentially curative treatment. Depending on the extent of the residual/recurrent disease, different surgical salvage options are at the surgeon's disposal. In selected cases with limited local disease, salvage transoral laser microsurgery, transoral robotic surgery and open partial laryngectomies can be employed to achieve cure while preserving laryngeal function. For more advanced cases total laryngectomy is necessary. Identifying situations with unacceptable results from surgical salvage may guide future therapies. (C) 2021 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. Show less
Purpose of review Observational studies have shown that serum 25-OH vitamin D [25(OH)D] is inversely associated with overall cancer risk in many malignancies. We performed a systematic literature... Show morePurpose of review Observational studies have shown that serum 25-OH vitamin D [25(OH)D] is inversely associated with overall cancer risk in many malignancies. We performed a systematic literature review to determine whether vitamin D deficiency is related to head and neck cancer (HNC) etiology and outcome. Recent findings The search yielded five prospective studies reporting 25(OH)D levels prior to cancer diagnosis and their effect on the risk of HNC. Eight studies were cross-sectional or case-control studies, in which 25(OH)D levels were only measured after cancer diagnosis. Two studies found an inverse association between 25(OH)D level and HNC risk, while two other prospective cohort studies demonstrated no connection between 25(OH)D and HNC risk. Several studies reported cancer patients to have significantly lower 25(OH)D levels than controls. Associations between 25(OH)D and prognosis and mortality were variable. The link between vitamin D and HNC has so far only been investigated in a few observational, prospective, and case-control studies. Vitamin D deficiency may be more common in HNC patients than in the healthy population. There is no evidence for a causal relationship. Further studies are needed to evaluate whether low 25(OH)D concentrations play a role in the development or outcome of HNCs. Show less
Background Squamous cell carcinoma (SCC) of the external auditory canal (EAC) is a rare disease, which is commonly classified with the modified Pittsburgh classification. Our aim was to evaluate... Show moreBackground Squamous cell carcinoma (SCC) of the external auditory canal (EAC) is a rare disease, which is commonly classified with the modified Pittsburgh classification. Our aim was to evaluate the predictive performance of this classification in relation to disease-free survival (DFS). Methods We examined retrospective data from a nationwide Dutch cohort study including patients with primary EAC SCC. These data were combined with individual patient data from the literature. Using the combined data, the predictive performances were calculated using the c-index. Results A total of 381 patients were included, 294 for clinical and 281 for the pathological classification analyses. The c-indices of the clinical and the pathological modified Pittsburgh classification predicting DFS were 0.725 (0.668-0.782) and 0.729 (0.672-0.786), respectively. Conclusion The predictive performance of the modified Pittsburgh classification system as such appears to be acceptable to predict the DFS of EAC SCC. Other factors need to be added to a future model to improve the predicted performance. Show less
Background: Larynx cancer is a common site for tumors of the upper aerodigestive tract. In cases with a clinically negative neck, the indications for an elective neck treatment are still debated.... Show moreBackground: Larynx cancer is a common site for tumors of the upper aerodigestive tract. In cases with a clinically negative neck, the indications for an elective neck treatment are still debated. The objective is to define the prevalence of occult metastasis based on the subsite of the primary tumor, T classification and neck node levels involved. Methods: All studies included provided the rate of occult metastases in cN0 larynx squamous cell carcinoma patients. The main outcome was the incidence of occult metastasis. The pooled incidence was calculated with random effects analysis. Results: 36 studies with 3803 patients fulfilled the criteria. The incidence of lymph node metastases for supraglottic and glottic tumors was 19.9% (95% CI 16.4-23.4) and 8.0% (95% CI 2.7-13.3), respectively. The incidence of occult metastasis for level I, level IV and level V was 2.4% (95% CI 0-6.1%), 2.0% (95% CI 0.9-3.1) and 0.4% (95% CI 0-1.0%), respectively. For all tumors, the incidence for sublevel IIB was 0.5% (95% CI 0-1.3). Conclusions: The incidence of occult lymph node metastasis is higher in supraglottic and T3-4 tumors. Level I and V and sublevel IIB should not be routinely included in the elective neck treatment of cN0 laryngeal cancer and, in addition, level IV should not be routinely included in cases of supraglottic tumors. Show less
Ridder, M. de; Balm, A.J.M.; Jong, R.J.B. de; Terhaard, C.H.J.; Takes, R.P.; Slingerland, M.; ... ; Dutch Head Neck Res Grp 2017
Purpose: To find molecular markers from expression profiling data to predict recurrence of laryngeal cancer after radiotherapy. Experimental Design: We generated gene expression data on pre... Show morePurpose: To find molecular markers from expression profiling data to predict recurrence of laryngeal cancer after radiotherapy. Experimental Design: We generated gene expression data on pre-treatment biopsies from 52 larynx cancer patients. Patients developing a local recurrence were matched for T-stage, subsite, treatment, gender and age with non-recurrence patients. Candidate genes were then tested by immunohistochemistry on tumor material from a second series of 76 patients. Both series comprised early stage cancer treated with radiotherapy alone. Finally, gene expression data of eight larynx cancer cell lines with known radiosensitivity were analyzed. Results: Nineteen patients with a local recurrence were matched with 33 controls. Gene sets for hypoxia, proliferation and intrinsic radiosensitivity did not correlate with recurrence, whereas expression of the putative stem cell marker CD44 did. In a supervised analysis, probes for all three splice variants of CD44 on the array appeared in the top 10 most significantly correlated with local recurrence. Immunohistochemical analysis of CD44 expression on the independent validation series confirmed CD44's predictive potential. In 8 larynx cancer cell lines, CD44 gene expression did not correlate with intrinsic radiosensitivity although it did correlate significantly with plating efficiency, consistent with a relationship with stem cell content. Conclusions: CD44 was the only biological factor tested which significantly correlated with response to radiotherapy in early stage larynx cancer patients, both at the mRNA and protein levels. Further studies are needed to confirm this and to assess how general these findings are for other head and neck tumor stages and sites. Clin Cancer Res; 16(21); 5329-38. (C) 2010 AACR. Show less
