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Purpose: Angiogenesis plays an important role in the growth and metastatic spread of solid tumours and is characterised by the expression of integrins on the cell surface of endothelial cells. Radiolabelled RGD peptides specifically target angiogenesis-related αvβ3 integrins, expressed on the activated endothelial cells of sprouting blood vessels. Here, we validated the feasibility of 68Ga[Ga]-DOTA-E-[c(RGDfK)]2 (68Ga-RGD) PET/CT to visualise angiogenesis in patients with oral squamous cell carcinoma (OSCC). Methods: Ten patients with OSCC and scheduled for surgical resection including elective neck dissection received an intravenously administration of 68Ga-RGD (42 ± 8 μg; 214 ± 9 MBq). All patients subsequently underwent dynamic (n = 5) or static PET/CT imaging (n = 5) for 60 min or for 4 min/bed position at 30, 60 and 90 min after injection, respectively. Quantitative tracer uptake in tumour lesions was expressed as standardised uptake values (SUV). Additionally, tumour tissue was immunohistochemically stained for αvβ3 integrin to assess the expression pattern. Results: 68Ga-RGD tumour accumulation was observed in all patients. At 60 min post injection, tumour SUVmax ranged between 4.0 and 12.7. Tracer accumulation in tumour tissue plateaued at 10 min after injection. Uptake in background tissue did not change over time, resulting in tumour-to-muscle tissue of 6.4 ± 0.7 at 60 min post injection. Conclusions: 68Ga-RGD PET/CT of αvβ3 integrin expression in OSCC patients is feasible with adequate tumour-to-background ratios. It will provide more insight in angiogenesis as a hallmark of the head and neck squamous cell carcinomas' tumour microenvironment. Trial registration: https://eudract.ema.europa.eu no. 2015-000917-31 [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the risk associated with different types of surgery for carotid body paraganglioma of different Shamblin class. A meta‐analysis was conducted to evaluate per tumour class, the local control, cranial nerve damage and complication rates of different techniques using internal carotid artery (ICA) and external carotid artery (ECA) ligation, clamping or bypassing, as well as the craniocaudal vs caudocranial techniques. Design: A meta‐analysis is conducted after a systematic search in PubMed and the Cochrane library, in accordance with the PRISMA guidelines. Main outcome measures: Local control, cranial nerve damage, complications, function recovery. Results: Out of 3565 articles, 27 were selected. The overall quality of evidence of studies was low. Cranial nerve damage (3%, 17% and 39%) and complication rates (0%, 1% and 10%) were significantly related to Shamblin class (class 1, 2 and 3, respectively, P < .01). For class 3 tumours, an increased risk of complications was found associated with routine ICA manipulation/reconstruction (RR 3.12 with a 95% CI of 1.29‐7.59), as well as a trend towards enhanced risk of routine ECA ligation (RR 3.48 with a 95% CI of 0.88‐13.81). Conclusions: For class 1 and 2 tumours, surgery seems a viable treatment option. For class 3 tumours, morbidity in terms of cranial nerve deficit and complications is considerable; particularly, the use of ICA manipulation/reconstruction and potentially ECA ligation seem to be accompanied by high stroke incidence. [ABSTRACT FROM AUTHOR]

Objective: Key for successful jugulotympanic paraganglioma management is a personalised approach aiming for the best practice for each individual patient. To this end, a systematic review is performed, evaluating the local control and complication rates for the different treatment modalities stratified by the broadly accepted Fisch classification. Design: A systematic literature review according to the PRISMA statement was performed. A detailed overview of individual treatment outcomes per Fisch class is provided. Main outcome measures: Local control, cranial nerve damage, complications, function recovery. Results: Eighteen studies were selected, resembling 83 patients treated with radiotherapy and 299 with surgery. Excellent local control was found post‐surgery for class A and B tumours, and risk of cranial nerve damage was <1%. For class C1‐4 tumours, local control was 80%‐95% post‐surgery (84% post‐radiotherapy), and cranial nerve damage was found in 71%‐76% (none post‐radiotherapy; P < .05). There was no difference in treatment outcomes between tumours of different C class. For class C1‐4De/Di tumours, local control was 38%‐86% (98% post‐radiotherapy; P < .05) and cranial nerve damage/complication rates were 67%‐100% (3% post‐radiotherapy; P < .05). C1‐4DeDi tumours showed lesser local control and cranial nerve damage rates when compared to C1‐4De tumours. Conclusions: An individual risk is constituted for surgery and radiotherapy, stratified per Fisch class. For class A and B tumours, surgery is a suitable treatment option. For class C and D tumours, radiotherapy results in lower complication rates and similar or better local control rates when compared to the surgical group. [ABSTRACT FROM AUTHOR]

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An abstract of the article "Effect of postoperative radiotherapy on the functional results of implants placed during ablative surgery for oral cancer," by R. H. Schepers, A. P. Slagter, J. H. A. M. Kaanders, F. J. A. van den Hoogen and M. A. Merkx is presented.

Background: Solitary fibrous tumors (SFT) are rare unusual ubiquitous soft tissue tumors that are presumed to be of fibroblastic differentiation. At present, the challenge is to establish accurate prognostic factors. Patients and methods: A total of 214 consecutive patients with SFT diagnosed in 24 participating cancer centers were entered into the European database (www.conticabase.org) to perform univariate and multivariate analysis for overall survival (OS), local recurrence incidence (LRI) and metastatic recurrence incidence (MRI) by taking competing risks into account. A prognostic model was constructed for LRI and MRI. Internal and external validations of the prognostic models were carried out. An individual risk calculator was carried out to quantify the risk of both local and metastatic recurrence. Results: We restricted our analysis to 162 patients with local disease. Twenty patients (12.3%) were deceased at the time of analysis and the median OS was not reached. The LRI rates at 10 and 20 years were 19.2% and 38.6%, respectively. The MRI rates at 10 and 20 years were 31.4% and 49.8%, respectively. Multivariate analysis retained age and mitotic count tended to significance for predicting OS. The factors influencing LRI were viscera localization, radiotherapy and age. Mitotic count, tumor localization other than limb and age had independent values for MRI. Three prognostic groups for OS were defined based on the number of unfavorable prognostic factors and calculations were carried out to predict the risk of local and metastatic recurrence for individual patients. Conclusion: LRI and MRI rates increased between 10 and 20 years so relapses were delayed, suggesting that long-term monitoring is useful. This study also shows that different prognostic SFT sub-groups could benefit from different therapeutic strategies and that use of a survival calculator could become standard practice in SFTs to individualize treatment based on the clinical situation. [ABSTRACT FROM AUTHOR]

Purpose: To study the feasibility of induction chemotherapy added to concomitant cisplatin-based chemoradiotherapy (CRT) in patients with locally advanced head and neck cancer (LAHNC). Patients and methods: LAHNC patients were treated with 4 courses of docetaxel/cisplatin/5-fluorouracil (TPF) followed by randomization to either cisplatin 100 mg/m2 with conventional radiotherapy (cis100 + RT) or cisplatin 40 mg/m2 weekly with accelerated radiotherapy (cis40 + ART). Primary endpoint was feasibility, defined as receiving ≥90% of the scheduled total radiation dose. Based on power analysis 70 patients were needed. Results: 65 patients were enrolled. The data safety monitoring board advised to prematurely terminate the study, because only 22% and 41% (32% in total) of the patients treated with cis100 + RT (n = 27) and cis40 + ART (n = 29) could receive the planned dose cisplatin during CRT, respectively, even though the primary endpoint was reached. Most common grade 3-4 toxicity was febrile neutropenia (18%) during TPF and dehydration (26% vs 14%), dysphagia (26% vs 24%) and mucositis (22% vs 57%) during cis100 + RT and cis40 + ART, respectively. For the patients treated with cis100 + RT and cis40 + ART, two years progression free survival and overall survival were 70% and 78% versus 72% and 79%, respectively. Conclusion: After TPF induction chemotherapy, cisplatin-containing CRT is not feasible in LAHNC patients, because the total planned cisplatin dose could only be administered in 32% of the patients due to toxicity. However, all but 2 patients received more than 90% of the planned radiotherapy. [ABSTRACT FROM AUTHOR]

Background and Purpose: Radiotherapy (RT) is a mainstay component of treatment for patients with head and neck squamous cell carcinoma (HNSCC), but responses vary. As RT relies upon oxidative damage, antioxidant expression in response to RT-induced reactive oxygen species (ROS) could compromise treatment response. We aimed to examine local and systemic antioxidant responses to increased RT-induced ROS in relation to treatment success., Materials and Methods: Nuclear factor erythroid 2-related factor 2 (NRF2), the main antioxidant transcription factor, was immunofluorescently stained in FaDu cells and in tumor biopsies of patients with oral cavity/oropharynx HNSCC before and after five fractions of RT. Besides, total antioxidant capacity (TAC) was analyzed in HNSCC tumor cells in vitro and in serum of HNSCC patients before, during, and after RT., Results: Data revealed an increase in NRF2 expression and TAC in head and neck cancer cells in vitro over the course of 5 daily fractions of 2 Gy. In accordance, also in patients' tumors NRF2 expression increased, which was associated with increased serum TAC during RT. Increasing serum TAC was related to impaired local tumor control., Conclusion: Radiation induced NRF2 expression and upregulated TAC, which may compromise the effect of RT-induced ROS. Changes in serum TAC during RT could serve as a novel predictor of treatment outcome in HNSCC patients.Medical Ethics Review Committee (CMO) approval - CMO number: 2007/104., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Elective 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/design: This 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., Discussion: If 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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Bloom Syndrome (BS) is a genetic DNA repair disorder, caused by mutations in the BLM gene. The clinical phenotype includes growth retardation, immunodeficiency and a strong predisposition to different types of malignancies. Treatment of malignancies in BS patients with radiotherapy or chemotherapy is believed to be associated with increased toxicity, but clinical and laboratory data are lacking. We collected clinical data of two Dutch BS patients with solid tumors. Both were treated with radiotherapy before the diagnosis BS was made and tolerated this treatment well. In addition, we collected fibroblasts from BS patients to perform in vitro clonogenic survival assays to determine radiosensitivity. BS fibroblasts showed less radiosensitivity than the severely radiosensitive Artemis fibroblasts. Moreover, studies of double strand break kinetics by counting 53BP1 foci after irradiation showed similar patterns compared to healthy controls. In combination, the clinical cases and laboratory experiments are valuable information in the discussion whether radiotherapy is absolutely contraindicated in BS, which is the Case in other DNA repair syndromes like Ataxia Telangiectasia and Artemis., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)