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Article ; Online: RNA processing machineries in Archaea: the 5'-3' exoribonuclease aRNase J of the β-CASP family is engaged specifically with the helicase ASH-Ski2 and the 3'-5' exoribonucleolytic RNA exosome machinery.

Phung, Duy Khanh / Etienne, Clarisse / Batista, Manon / Langendijk-Genevaux, Petra / Moalic, Yann / Laurent, Sébastien / Liuu, Sophie / Morales, Violette / Jebbar, Mohamed / Fichant, Gwennaele / Bouvier, Marie / Flament, Didier / Clouet-d'Orval, Béatrice

Nucleic acids research

2020 Volume 48, Issue 7, Page(s) 3832–3847

Abstract: ... that aRNase J, a 5'-3' exoribonuclease of the β-CASP family conserved in Euryarchaeota, engages specifically ... strengthened by comprehensive phylogenomic studies demonstrated that aRNase J interplay with ASH-Ski2 and a cap ... evidences that an aRNase J/ASH-Ski2 complex might exist in vivo and hint at an association of aRNase J ...

Abstract	A network of RNA helicases, endoribonucleases and exoribonucleases regulates the quantity and quality of cellular RNAs. To date, mechanistic studies focussed on bacterial and eukaryal systems due to the challenge of identifying the main drivers of RNA decay and processing in Archaea. Here, our data support that aRNase J, a 5'-3' exoribonuclease of the β-CASP family conserved in Euryarchaeota, engages specifically with a Ski2-like helicase and the RNA exosome to potentially exert control over RNA surveillance, at the vicinity of the ribosome. Proteomic landscapes and direct protein-protein interaction analyses, strengthened by comprehensive phylogenomic studies demonstrated that aRNase J interplay with ASH-Ski2 and a cap exosome subunit. Finally, Thermococcus barophilus whole-cell extract fractionation experiments provide evidences that an aRNase J/ASH-Ski2 complex might exist in vivo and hint at an association of aRNase J with the ribosome that is emphasised in absence of ASH-Ski2. Whilst aRNase J homologues are found among bacteria, the RNA exosome and the Ski2-like RNA helicase have eukaryotic homologues, underlining the mosaic aspect of archaeal RNA machines. Altogether, these results suggest a fundamental role of β-CASP RNase/helicase complex in archaeal RNA metabolism.
MeSH term(s)	Euryarchaeota/enzymology ; Exoribonucleases/metabolism ; Exosome Multienzyme Ribonuclease Complex/metabolism ; Protein Interaction Mapping ; Pyrococcus abyssi/enzymology ; RNA Helicases/metabolism ; RNA Processing, Post-Transcriptional ; RNA, Archaeal/metabolism ; Thermococcus/enzymology
Chemical Substances	RNA, Archaeal ; Exoribonucleases (EC 3.1.-) ; Exosome Multienzyme Ribonuclease Complex (EC 3.1.-) ; RNA Helicases (EC 3.6.4.13)
Language	English
Publishing date	2020-02-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkaa052
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Article ; Online: Reply to the editor: Potential contributors to implant losses following radiotherapy or chemoradiotherapy.

Alberga, Jamie M / Vissink, Arjan / Korfage, Anke / de Visscher, Sebastiaan A H J / Witjes, Max J H / Langendijk, Johannes A / Raghoebar, Gerry M

Oral diseases

2024

Language	English
Publishing date	2024-02-20
Publishing country	Denmark
Document type	Letter
ZDB-ID	1290529-x
ISSN	1601-0825 ; 1354-523X
ISSN (online)	1601-0825
ISSN	1354-523X
DOI	10.1111/odi.14888
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Zs.A 4427: Show issues

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Article ; Online: Head and neck cancer patients with geriatric deficits are more often non-responders and lost from follow-up in quality of life studies.

de Vries, Julius / Vermue, Dannie J / Sidorenkov, Grigory / Festen, Suzanne / Langendijk, Johannes A / de Bock, Geertruida H / Halmos, Gyorgy B

European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery

2024 Volume 281, Issue 5, Page(s) 2619–2626

Abstract: Objectives: To identify associations between frailty and non-response to follow-up questionnaires, in a longitudinal head and neck cancer (HNC) study with patient-reported outcome measures (PROMs).: Materials and methods: Patients referred with HNC ... ...

Abstract	Objectives: To identify associations between frailty and non-response to follow-up questionnaires, in a longitudinal head and neck cancer (HNC) study with patient-reported outcome measures (PROMs). Materials and methods: Patients referred with HNC were included in OncoLifeS, a prospective data-biobank, underwent Geriatric Assessment (GA) and frailty screening ahead of treatment, and were followed up at 3, 6, 12 and 24 months after treatment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Head and Neck 35. Statistical analysis for factors associated with non-response was done using Generalized Linear Mixed Models. Results: 289 patients were eligible for analysis. Mean age was 68.4 years and 68.5% were male. Restrictions in Activities of Daily Living [OR 4.46 (2.04-9.78)] and Instrumental Activities of Daily Living [OR 4.33 (2.27-8.24)], impaired mobility on Timed Up and Go test [OR 3.95 (1.85-8.45)], cognitive decline [OR 4.85 (2.28-10.35)] and assisted living (OR 5.54 (2.63-11.67)] were significantly associated with non-response. Frailty screening, with Geriatric 8 and Groningen Frailty Indicator, was also associated with non-response [OR, respectively, 2.64 (1.51-4.59) and 2.52 (1.44-4.44)]. All findings remained significant when adjusted for other factors that were significantly associated with non-response, such as higher age, longer study duration and subsequent death. Conclusion: Frail HNC patients respond significantly worse to follow-up PROMs. The drop-out and underrepresentation of frail patients in studies may lead to attrition bias, and as a result underestimating the effect sizes of associations. This is of importance when handling and interpreting such data.
MeSH term(s)	Humans ; Male ; Aged ; Female ; Frailty/complications ; Frailty/diagnosis ; Frail Elderly ; Quality of Life ; Follow-Up Studies ; Prospective Studies ; Activities of Daily Living ; Postural Balance ; Time and Motion Studies ; Head and Neck Neoplasms/complications ; Head and Neck Neoplasms/therapy ; Geriatric Assessment
Language	English
Publishing date	2024-03-01
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1017359-6
ISSN	1434-4726 ; 0937-4477
ISSN (online)	1434-4726
ISSN	0937-4477
DOI	10.1007/s00405-024-08528-w
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Article ; Online: Technical note: Evaluation of deep learning based synthetic CTs clinical readiness for dose and NTCP driven head and neck adaptive proton therapy.

de Koster, Rutger J C / Thummerer, Adrian / Scandurra, Daniel / Langendijk, Johannes A / Both, Stefan

Medical physics

2023 Volume 50, Issue 12, Page(s) 8023–8033

Abstract: Background: Adaptive proton therapy workflows rely on accurate imaging throughout the treatment course. Our centre currently utilizes weekly repeat CTs (rCTs) for treatment monitoring and plan adaptations. However, deep learning-based methods have ... ...

Abstract	Background: Adaptive proton therapy workflows rely on accurate imaging throughout the treatment course. Our centre currently utilizes weekly repeat CTs (rCTs) for treatment monitoring and plan adaptations. However, deep learning-based methods have recently shown to successfully correct CBCT images, which suffer from severe imaging artifacts, and generate high quality synthetic CT (sCT) images which enable CBCT-based proton dose calculations. Purpose: To compare daily CBCT-based sCT images to planning CTs (pCT) and rCTs of head and neck (HN) cancer patients to investigate the dosimetric accuracy of CBCT-based sCTs in a scenario mimicking actual clinical practice. Methods: Data of 56 HN cancer patients, previously treated with proton therapy was used to generate 1.962 sCT images, using a previously developed and trained deep convolutional neural network. Clinical IMPT treatment plans were recalculated on the pCT, weekly rCTs and daily sCTs. The dosimetric accuracy of sCTs was compared to same day rCTs and the initial planning CT. As a reference, rCTs were also compared to pCTs. The dose difference between sCTs and rCTs/pCT was quantified by calculating the D Results: For target volumes, only minor dose differences were found for sCT versus rCT and sCT versus pCT, with dose differences mostly within ±1.5%. Larger dose differences were observed in OARs, where a general shift towards positive differences was found, with the largest difference in the left parotid gland. Delta NTCP values for grade 2 dysphagia and xerostomia were within ±2.5% for 90% of the sCTs. Conclusions: Target doses showed high similarity between rCTs and sCTs. Further investigations are required to identify the origin of the dose differences at OAR levels and its relevance in clinical decision making.
MeSH term(s)	Humans ; Deep Learning ; Proton Therapy/methods ; Deglutition Disorders ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted/methods ; Head and Neck Neoplasms/diagnostic imaging ; Head and Neck Neoplasms/radiotherapy ; Cone-Beam Computed Tomography ; Xerostomia ; Radiotherapy, Intensity-Modulated/methods
Language	English
Publishing date	2023-10-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	188780-4
ISSN	2473-4209 ; 0094-2405
ISSN (online)	2473-4209
ISSN	0094-2405
DOI	10.1002/mp.16782
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Article ; Online: Site-specific radiation dosage and implant survival in oral cancer patients: A cohort study.

Alberga, Jamie M / Vissink, Arjan / Korfage, Anke / de Visscher, Sebastiaan A H J / Witjes, Max J H / Langendijk, Johannes A / Raghoebar, Gerry M

Oral diseases

2023

Abstract: Objectives: We assessed the radiation dosages (D: Materials and methods: Data was collected prospectively from 28 patients treated surgically for an intraoral malignancy, followed by postoperative radiotherapy (VMAT) and analyzed retrospectively. ... ...

Abstract	Objectives: We assessed the radiation dosages (D Materials and methods: Data was collected prospectively from 28 patients treated surgically for an intraoral malignancy, followed by postoperative radiotherapy (VMAT) and analyzed retrospectively. Patients received 2 implants in the native mandible during ablative surgery. Implant-specific D Results: Five out of 56 placed implants were lost during follow-up (median 36.0 months, IQR 39.0). Radiographically, peri-implant bone loss occurred in implants with a D Conclusion: An implant-specific D
Language	English
Publishing date	2023-11-20
Publishing country	Denmark
Document type	Journal Article
ZDB-ID	1290529-x
ISSN	1601-0825 ; 1354-523X
ISSN (online)	1601-0825
ISSN	1354-523X
DOI	10.1111/odi.14813
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Article ; Online: Comparing supervised and semi-supervised machine learning approaches in NTCP modeling to predict complications in head and neck cancer patients.

Spiero, I / Schuit, E / Wijers, O B / Hoebers, F J P / Langendijk, J A / Leeuwenberg, A M

Clinical and translational radiation oncology

2023 Volume 43, Page(s) 100677

Abstract: Background and purpose: Head and neck cancer (HNC) patients treated with radiotherapy often suffer from radiation-induced toxicities. Normal Tissue Complication Probability (NTCP) modeling can be used to determine the probability to develop these ... ...

Abstract	Background and purpose: Head and neck cancer (HNC) patients treated with radiotherapy often suffer from radiation-induced toxicities. Normal Tissue Complication Probability (NTCP) modeling can be used to determine the probability to develop these toxicities based on patient, tumor, treatment and dose characteristics. Since the currently used NTCP models are developed using supervised methods that discard unlabeled patient data, we assessed whether the addition of unlabeled patient data by using semi-supervised modeling would gain predictive performance. Materials and methods: The semi-supervised method of self-training was compared to supervised regression methods with and without prior multiple imputation by chained equation (MICE). The models were developed for the most common toxicity outcomes in HNC patients, xerostomia (dry mouth) and dysphagia (difficulty swallowing), measured at six months after treatment, in a development cohort of 750 HNC patients. The models were externally validated in a validation cohort of 395 HNC patients. Model performance was assessed by discrimination and calibration. Results: MICE and self-training did not improve performance in terms of discrimination or calibration at external validation compared to current regression models. In addition, the relative performance of the different models did not change upon a decrease in the amount of (labeled) data available for model development. Models using ridge regression outperformed the logistic models for the dysphagia outcome. Conclusion: Since there was no apparent gain in the addition of unlabeled patient data by using the semi-supervised method of self-training or MICE, the supervised regression models would still be preferred in current NTCP modeling for HNC patients.
Language	English
Publishing date	2023-09-21
Publishing country	Ireland
Document type	Journal Article
ISSN	2405-6308
ISSN (online)	2405-6308
DOI	10.1016/j.ctro.2023.100677
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Article ; Online: Evaluation of a new two-step frailty assessment of head and neck patients in a prospective cohort.

Padovan, Beniamino Vincenzoni / Bijl, M A J / Langendijk, J A / van der Laan, H P / Van Dijk, B A C / Festen, S / Halmos, G B

2024

Abstract: Purpose: Assessing frailty, in head and neck cancer (HNC) patients is key when choosing appropriate treatment. Optimal screening is challenging, as it should be feasible and should avoid over-referral for comprehensive geriatric assessment (CGA) This ... ...

Abstract	Purpose: Assessing frailty, in head and neck cancer (HNC) patients is key when choosing appropriate treatment. Optimal screening is challenging, as it should be feasible and should avoid over-referral for comprehensive geriatric assessment (CGA) This study aims to evaluate the association between geriatric assessment using a new two-step care pathway, referral to geriatrician and adverse outcomes. Methods: This institutional retrospective analysis on a prospective cohort analysed the multimodal geriatric assessment (GA) of newly diagnosed HNC patients. Uni- and multivariable logistic regression was performed to study the association between the screening tests, and referral to the geriatrician for complete geriatric screening, and adverse outcomes. Results: This study included 539 patients, of whom 276 were screened. Patients who underwent the GA, were significantly older and more often had advanced tumour stages compared to non-screened patients. Referral to the geriatrician was done for 30.8% of patients. Of the 130 patients who underwent surgery, 26/130 (20%) experienced clinically relevant postoperative complications. Of the 184 patients who underwent (radio)chemotherapy, 50/184 (27.2%) had clinically relevant treatment-related toxicity. Age, treatment intensity, polypharmacy and cognitive deficits, were independently associated with referral to geriatrician. A medium to high risk of malnutrition was independently associated with acute radiation induced toxicity and adverse outcomes in general. Conclusion: The current study showed a 30.8% referral rate for CGA by a geriatrician. Age, treatment intensity, cognitive deficits and polypharmacy were associated with higher rates of referral. Furthermore, nutritional status was found to be an important negative factor for adverse treatment outcomes, that requires attention.
Language	English
Publishing date	2024-04-23
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1017359-6
ISSN	1434-4726 ; 0937-4477
ISSN (online)	1434-4726
ISSN	0937-4477
DOI	10.1007/s00405-024-08651-8
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Article: Skeletal

Janssen, Jorinde / Noordzij, Walter / Velleman, Ton / de Jong, Igle Jan / Langendijk, Johannes A / Verzijlbergen, J Fred / Stormezand, Gilles N / Aluwini, Shafak

Therapeutic advances in medical oncology

2023 Volume 15, Page(s) 17588359231179311

Abstract: Background/objectives: Accurate and uniform interpretation and reporting of metastatic prostate cancer (PCa) lesions on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) are indispensable. : Design/ ... ...

Abstract	Background/objectives: Accurate and uniform interpretation and reporting of metastatic prostate cancer (PCa) lesions on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) are indispensable. Design/methods: In total, 33 Results: Observers qualified most lesions as not malignant (81-91%) and the overall mean interobserver agreement was moderate on both patient (κ: 0.54) and lesion level (κ: 0.55). In 52 lesions without corresponding CT substrate, the rating resulted in not malignant in 95-100%. Availability of additional imaging (60% of lesions) did not improve interobserver agreement (κ: 0.39 on lesion level) and resulted in unchanged rating for all observers in 78%. Conclusion: This interobserver analysis of skeletal
Language	English
Publishing date	2023-06-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2503443-1
ISSN	1758-8359 ; 1758-8340
ISSN (online)	1758-8359
ISSN	1758-8340
DOI	10.1177/17588359231179311
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Article ; Online: Prediction of Radiation-Induced Parotid Gland-Related Xerostomia in Patients With Head and Neck Cancer: Regeneration-Weighted Dose.

van Rijn-Dekker, Maria I / van Luijk, Peter / Schuit, Ewoud / van der Schaaf, Arjen / Langendijk, Johannes A / Steenbakkers, Roel J H M

International journal of radiation oncology, biology, physics

2023 Volume 117, Issue 3, Page(s) 750–762

Abstract: Purpose: Despite improvements to treatment, patients with head and neck cancer (HNC) still experience radiation-induced xerostomia due to salivary gland damage. The stem cells of the parotid gland (PG), concentrated in the gland's main ducts (stem cell ... ...

Abstract	Purpose: Despite improvements to treatment, patients with head and neck cancer (HNC) still experience radiation-induced xerostomia due to salivary gland damage. The stem cells of the parotid gland (PG), concentrated in the gland's main ducts (stem cell rich [SCR] region), play a critical role in the PG's response to radiation. Treatment optimization requires a dose metric that properly accounts for the relative contributions of dose to this SCR region and the PG's remainder (non-SCR region) to the risk of xerostomia in normal tissue complication probability (NTCP) models for xerostomia. Materials and methods: Treatment and toxicity data of 1013 prospectively followed patients with HNC treated with definitive radiation therapy (RT) were used. The regeneration-weighted dose, enabling accounting for the hypothesized different effects of dose to the SCR and non-SCR region on the risk of xerostomia, was defined as D Results: Dose to the contralateral PG was associated with daytime, eating-related, and physician-rated grade ≥2 xerostomia. Consequently, r was estimated and found to be smaller than 3.6 for most PG function-related endpoints. Therefore, the contribution of D Conclusions: Tools for clinical implementation of stem cell sparing RT were developed: regeneration-weighted dose to the parotid gland that accounted for regional differences in radiosensitivity within the gland and NTCP models that included this new dose metric and other prognostic factors.
MeSH term(s)	Humans ; Parotid Gland/radiation effects ; Xerostomia/etiology ; Head and Neck Neoplasms/radiotherapy ; Head and Neck Neoplasms/complications ; Salivary Glands/radiation effects ; Radiation Injuries/complications ; Regeneration
Language	English
Publishing date	2023-05-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	197614-x
ISSN	1879-355X ; 0360-3016
ISSN (online)	1879-355X
ISSN	0360-3016
DOI	10.1016/j.ijrobp.2023.04.034
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Article ; Online: Radiation-induced xerostomia is related to stem cell dose-dependent reduction of saliva production.

van Rijn-Dekker, Maria I / la Bastide-van Gemert, Sacha / Stokman, Monique A / Vissink, Arjan / Coppes, Robert P / Langendijk, Johannes A / van Luijk, Peter / Steenbakkers, Roel J H M

International journal of radiation oncology, biology, physics

2024

Abstract: Background and purpose: Previous studies have shown that the mean dose to the parotid gland stem cell rich regions (D: Material/methods: In 570 head and neck cancer patients treated with definitive radiation therapy (RT), flow from the parotid (FLOW!# ...

Abstract	Background and purpose: Previous studies have shown that the mean dose to the parotid gland stem cell rich regions (D Material/methods: In 570 head and neck cancer patients treated with definitive radiation therapy (RT), flow from the parotid (FLOW Results: D Conclusion: Higher SCR region dose reduced parotid gland saliva production, subsequently resulting in higher daytime xerostomia scores. Consequently, this study supports the clinical implementation of stem cell sparing RT to preserve salivary flow with the aim of reducing the risk of xerostomia.
Language	English
Publishing date	2024-04-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	197614-x
ISSN	1879-355X ; 0360-3016
ISSN (online)	1879-355X
ISSN	0360-3016
DOI	10.1016/j.ijrobp.2024.04.012
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