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Article ; Online: Is stereotactic body radiotherapy an effective treatment in metastatic lung cancer with oligoprogressive disease?

Aquilano, Michele / Loi, Mauro / Visani, Luca / Livi, Lorenzo / Nuyttens, Joost J

2023 Volume 62, Issue 3, Page(s) 298–304

Abstract: Background: Oligoprogression (OPD) is defined as a condition where limited progression (1-3 metastases) is observed in patients undergoing systemic cancer treatment. In this study we investigated the impact of stereotactic body radiotherapy (SBRT) in ... ...

Abstract	Background: Oligoprogression (OPD) is defined as a condition where limited progression (1-3 metastases) is observed in patients undergoing systemic cancer treatment. In this study we investigated the impact of stereotactic body radiotherapy (SBRT) in patients with OPD from metastatic lung cancer. Material and methods: Data from a cohort of consecutive patients with SBRT treated between June 2015 and August 2021 were collected. All extracranial metastatic sites of OPD from lung cancer were included. Dose regimens consisted of mainly 24 in 2 fractions, 30-51 Gy in 3 fractions, 30-55 Gy in 5 fractions, 52.5 Gy in 7 fractions and 44-56 Gy in 8 fractions. Kaplan-Meier method was used to calculate Overall Survival (OS), Local Control (LC), and Disease-Free Survival (DFS) from the start date of SBRT to the event. Results: Sixty-three patients, 34 female and 29 males were included. Median age was 75 years (range 25-83). All patients received concurrent systemic treatment before the start of the SBRT: 19 chemotherapy (CT), 26 CT plus immunotherapy (IT) or Tyrosin kinase inhibitors (TKI) and 18 IT/TKI. SBRT was delivered to the lung ( Conclusions: Median DFS was 7 months, translating into the continuation of effective systemic treatment as other metastases grow slowly. In patients with oligoprogression disease, SBRT is a valid and efficient treatment that may enable postponing the switch of systemic line.
MeSH term(s)	Male ; Humans ; Female ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Radiosurgery/methods ; Prognosis ; Retrospective Studies ; Treatment Outcome ; Lung Neoplasms/pathology
Language	English
Publishing date	2023-03-11
Publishing country	England
Document type	Journal Article
ZDB-ID	896449-x
ISSN	1651-226X ; 0349-652X ; 0284-186X ; 1100-1704
ISSN (online)	1651-226X
ISSN	0349-652X ; 0284-186X ; 1100-1704
DOI	10.1080/0284186X.2023.2186187
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Zs.A 6348: Show issues

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Article: Survival and Prognostic Factors of Ultra-Central Tumors Treated with Stereotactic Body Radiotherapy.

Salvestrini, Viola / Duijm, Marloes / Loi, Mauro / Nuyttens, Joost J

Cancers

2022 Volume 14, Issue 23

Abstract: Introduction: Stereotactic body radiotherapy (SBRT) reported excellent outcomes and a good tolerability profile in case of central lung tumors, as long as risk-adapted schedules were adopted. High grade toxicity was more frequently observed for tumors ... ...

Abstract	Introduction: Stereotactic body radiotherapy (SBRT) reported excellent outcomes and a good tolerability profile in case of central lung tumors, as long as risk-adapted schedules were adopted. High grade toxicity was more frequently observed for tumors directly touching or overlapping the trachea, proximal bronchial tree (PBT), and esophagus. We aim to identify prognostic factors associated with survival for Ultra-Central (UC) tumors. Methods: We retrospectively evaluated patients treated with SBRT for primary or metastatic UC lung tumors. SBRT schedules ranged from 45 to 60 Gy. Results: A total number of 126 ultra-central lung tumors were reviewed. The Median follow-up time was 23 months. Median Overall Survival (OS) and Progression Free Survival (PFS) was 29.3 months and 16 months, respectively. Local Control (LC) rates at 1 and 2 were 86% and 78%, respectively. Female gender, age < 70 years, and tumor size < 5 cm were significantly associated with better OS. The group of patients with tumors close to the trachea but further away from the PBT also correlated with better OS. The acute G2 dysphagia, cough, and dyspnea were 11%, 5%, and 3%, respectively. Acute G3 dyspnea was experienced by one patient. Late G3 toxicity was reported in 4% of patients. Conclusion: risk-adaptive SBRT for ultra-central tumors is safe and effective, even if it remains a high-risk clinical scenario.
Language	English
Publishing date	2022-11-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14235908
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Article ; Online: Trade-off in healthy tissue sparing of FLASH and fractionation in stereotactic proton therapy of lung lesions with transmission beams.

Habraken, Steven / Breedveld, Sebastiaan / Groen, Jort / Nuyttens, Joost / Hoogeman, Mischa

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

2022 Volume 175, Page(s) 231–237

Abstract: Purpose and objective: Besides a dose-rate threshold of 40-100 Gy/s, the FLASH effect may require a dose > 3.5-7 Gy. Even in hypofractioned treatments, with all beams delivered in each fraction (ABEF), most healthy tissue is irradiated to a lower ... ...

Abstract	Purpose and objective: Besides a dose-rate threshold of 40-100 Gy/s, the FLASH effect may require a dose > 3.5-7 Gy. Even in hypofractioned treatments, with all beams delivered in each fraction (ABEF), most healthy tissue is irradiated to a lower fraction dose. This can be circumvented by single-beam-per-fraction (SBPF) delivery, with a loss of healthy tissue sparing by fractionation. We investigated the trade-off between FLASH and loss of fractionation in SBPF stereotactic proton therapy of lung cancer and determined break-even FLASH-enhancement ratios (FERs). Materials and methods: Treatment plans for 12 patients were generated. GTV delineations were available and a 5 mm GTV-PTV margin was applied. Equiangular arrangements of 3, 5, 7, and 9 244 MeV proton transmission beams were used. To facilitate SBPF, the number of fractions was equal to the number of beams. Iso-effective fractionation schedules with a single field uniform dose prescription were used: D Results: Compared to ABEF, SBPF resulted in a median increase of EQD2 Conclusion: A FLASH effect outweighing the loss of fractionation in SBPF may be achieved in stereotactic lung treatments. The trade-off with fractionation depends on the conditions under which the FLASH effect occurs. Better understanding of the underlying biology and the impact of delivery conditions is needed.
MeSH term(s)	Humans ; Proton Therapy/methods ; Radiotherapy Planning, Computer-Assisted/methods ; Radiotherapy Dosage ; Radiotherapy, Intensity-Modulated/methods ; Radiosurgery/methods ; Protons ; Lung Neoplasms/pathology ; Lung/pathology
Chemical Substances	Protons
Language	English
Publishing date	2022-08-18
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	605646-5
ISSN	1879-0887 ; 0167-8140
ISSN (online)	1879-0887
ISSN	0167-8140
DOI	10.1016/j.radonc.2022.08.015
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Zs.A 1926: Show issues

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Article ; Online: Adjuvant Therapy for Patients with a Tumor-Positive Resection Margin After Neoadjuvant Chemoradiotherapy and Esophagectomy.

van der Zijden, C J / van der Sluis, P C / Mostert, B / Nuyttens, J J M E / Spaander, V M C W / Valkema, R / Ruurda, J P / Wijnhoven, B P L / Lagarde, S M

Annals of surgical oncology

2024

Abstract: Background: Approximately 4-9% of patients have a tumor-positive resection margin after neoadjuvant chemoradiotherapy (nCRT) and esophagectomy. Although it is associated with decreased survival, Western guidelines do not recommend adjuvant treatment.: ...

Abstract	Background: Approximately 4-9% of patients have a tumor-positive resection margin after neoadjuvant chemoradiotherapy (nCRT) and esophagectomy. Although it is associated with decreased survival, Western guidelines do not recommend adjuvant treatment. Objective: The aim of this study was to assess the proportion of patients who received adjuvant therapy, and to evaluate overall survival (OS) after esophagectomy in patients with a tumor-positive resection margin. Methods: Patients diagnosed with resectable (cT2-4a/cTxN0-3/NxM0) esophageal cancer between 2015 and 2022, and treated with nCRT followed by irradical esophagectomy, were selected from the Netherlands Cancer Registry. The primary outcome was the proportion of patients with a tumor-positive resection margin who started adjuvant treatment ≤16 weeks after esophagectomy, including chemotherapy/radiotherapy, immunotherapy, or targeted therapy. OS was calculated from the date of surgery until the date of death or last day of follow-up. Results: Overall, 376 patients were included in our study, of whom 357 were treated with nCRT. Of these 357 patients, 98.3% had a microscopically irradical resection and 1.7% had a macroscopically irradical resection. Approximately 72.3% of tumors showed a partial response (Mandard 2-3) and 11.8% showed little/no pathological response (Mandard 4-5) to nCRT. One of 357 patients underwent adjuvant chemoradiotherapy and 39 patients (61%) underwent adjuvant immunotherapy (nivolumab). The median and 5-year OS rate of all patients was 16.4 months (95% confidence interval 13.1-19.8) and 21%, respectively. Conclusion: Real-world population-level data showed that no patients with a tumor-positive resection margin underwent adjuvant therapy following nCRT and esophagectomy prior to 2021. Interestingly, 61% of patients were treated with adjuvant nivolumab in 2021-2022. OS after irradical esophagectomy is poor and long-term data will explore the added value of nivolumab.
Language	English
Publishing date	2024-01-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	1200469-8
ISSN	1534-4681 ; 1068-9265
ISSN (online)	1534-4681
ISSN	1068-9265
DOI	10.1245/s10434-024-14912-x
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Zs.A 4042: Show issues

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Article: Basophil activation test with progressively less heated forms of egg distinguishes egg allergic from tolerant children.

De Vlieger, L / Nuyttens, L / Ieven, T / Diels, M / Coorevits, L / Cremer, J / Schrijvers, R / Bullens, D Ma

Journal of investigational allergology & clinical immunology

2023

Abstract: Background and objective: Diagnosis of egg allergy through basophil activation testing (BAT) has been mainly performed with an egg white extract or individual egg allergens rather than clinically more representative whole-egg extracts. Impact of heating ...

Abstract	Background and objective: Diagnosis of egg allergy through basophil activation testing (BAT) has been mainly performed with an egg white extract or individual egg allergens rather than clinically more representative whole-egg extracts. Impact of heating on whole-egg extract allergenicity remains unassessed.Validating BAT with gradually less heated whole-egg extracts in egg allergy diagnosis and as tolerance marker. Methods: CD63-based BAT was performed with five progressively less heated extracts from cake, hard-boiled egg, omelet, soft-boiled, and raw egg in 10 egg allergic (EA), 10 complete egg tolerant (ET) and 12 non-egg-sensitized non-allergic (NEA) children. Cutoffs and diagnostic accuracy measures were established through ROC analysis. Changes in basophil response were assessed in 12 baked egg tolerant children undergoing an 8-month gradual egg reintroduction protocol with BAT and oral food challenges prior to each reintroduction step. Results: Basophil responses to all egg extracts were increased in EA, but not in ET and NEA children. Responses decreased progressively with more heated egg extracts. Compared to ET children, EA children showed higher basophil sensitivity for all egg extracts. Negative BAT responses predicted clinical tolerance with a 90-100% sensitivity, 100% specificity, and false positive rate of 2.78%. In comparison, egg sIgE's (<0.35 kUA/L) had a lower specificity of 50-78% with a false positive rate of 40%. Basophil reactivity and sensitivity tended to decrease in baked egg tolerant children undergoing gradual egg reintroduction, concurrent with tolerance development. Conclusion: BAT with progressively less heated egg preparations is a sensitive and highly specific tool to discriminate EA from ET children.
Language	English
Publishing date	2023-11-07
Publishing country	Spain
Document type	Journal Article
ZDB-ID	1128657-x
ISSN	1018-9068
ISSN	1018-9068
DOI	10.18176/jiaci.0964
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Zs.A 3487: Show issues

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Article ; Online: Direct lysis of 3D cell cultures for RT-qPCR gene expression quantification.

Gysens, Fien / Ostyn, Lisa / Goeteyn, Ellen / Blondeel, Eva / Nuyttens, Justine / De Wever, Olivier / de Bony, Eric / Crabbé, Aurélie / Mestdagh, Pieter

Scientific reports

2023 Volume 13, Issue 1, Page(s) 1520

Abstract: In vitro cell culture experiments are widely used to study cellular behavior in most biological research fields. Except for suspension cells, most human cell types are cultured as adherent monolayers on a plastic surface. While technically convenient, ... ...

Abstract	In vitro cell culture experiments are widely used to study cellular behavior in most biological research fields. Except for suspension cells, most human cell types are cultured as adherent monolayers on a plastic surface. While technically convenient, monolayer cultures can suffer from limitations in terms of physiological relevance, as their resemblance to complex in vivo tissue structures is limited. To address these limitations, three-dimensional (3D) cell culture systems have gained increased interest as they mimic key structural and functional properties of their in vivo tissue counterparts. Nevertheless, protocols established on monolayer cell cultures may require adjustments if they are to be applied to 3D cell cultures. As gene expression quantification is an essential part of many in vitro experiments, we evaluated and optimized a direct cell lysis, reverse transcription and qPCR protocol applicable for 3D cell cultures. The newly developed protocol wherein gene expression is determined directly from crude cell lysates showed improved cell lysis compared to the standard protocol, accurate gene expression quantification, hereby avoiding time-consuming cell harvesting and RNA extraction.
MeSH term(s)	Humans ; Cell Culture Techniques/methods ; Cell Culture Techniques, Three Dimensional ; Gene Expression
Language	English
Publishing date	2023-01-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-28844-1
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Article ; Online: Judging a Fish by Its Ability to Climb a Tree? A Call for Novel Endpoints in the Appraisal of Ablative Local Treatments of Oligometastatic Cancer.

Loi, Mauro / Alifano, Marco / Scorsetti, Marta / Nuyttens, Joost J / Livi, Lorenzo

The oncologist

2021 Volume 26, Issue 6, Page(s) e1085–e1086

MeSH term(s)	Carcinoma, Non-Small-Cell Lung ; Humans ; Lung Neoplasms/surgery ; Neoplasm Metastasis ; Radiosurgery ; Trees
Language	English
Publishing date	2021-04-09
Publishing country	United States
Document type	Letter
ZDB-ID	1409038-7
ISSN	1549-490X ; 1083-7159
ISSN (online)	1549-490X
ISSN	1083-7159
DOI	10.1002/onco.13747
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Zs.A 4845: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 494: Show issues

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Article ; Online: Brain Metastases: Patient-Reported Outcome and Quality of Life after Whole-Brain Radiotherapy.

Otto-Vollaard, Lijanne / Quint, Sandra / de Pree, Ilse M N / Steinvoort, Illona N / Tims, Olijn J L / Nuyttens, Joost J

Journal of palliative medicine

2022 Volume 25, Issue 10, Page(s) 1533–1539

Abstract: ... Purpose: ... The aim of this prospective cohort study was to determine the outcome and quality of life (QoL) for patients with brain metastases treated with whole-brain radiotherapy (WBRT). ... Materials and Methods: ... WBRT was given to ...

Abstract	*Purpose:* The aim of this prospective cohort study was to determine the outcome and quality of life (QoL) for patients with brain metastases treated with whole-brain radiotherapy (WBRT). *Materials and Methods:* WBRT was given to 162 patients. Treatment outcome was reported through telephone consultation at four and eight weeks after the last fraction of the treatment. Treatment outcome was scored as a benefit when patients reported positively on the question whether radiotherapy of the whole brain did relieve their complaints. Patients who scored the treatment as beneficial were categorized as responders. The European Organization for Research and Treatment of Cancer (EORTC) questionnaire QLQ-C15-PAL was scored at day 0 and eight weeks after the last fraction of WBRT. *Results:* Patients who were alive after 2 months and reported benefit from treatment had a median survival of 8.1 months compared with 2.9 months for patients who reported no benefit. Forty-three patients died within two months (27%). Median overall survival was 3.5 months. Improvement of neurological symptoms was the most commonly reported benefit of the treatment. The responders had significantly better sleep (p = 0.032) and were less tense (p = 0.014). The nonresponders were also less tense (p = 0.042), but had less appetite (p = 0.023), felt weaker (p = 0.011), and experienced more fatigue (p = 0.001). *Conclusions:* WBRT is effective in a selected group of patients. Forty-nine percent of the patients surviving two months reported benefit from the treatment, resulting in a significantly increased survival rate for this group. However, 27% of patients died within two months. QoL increased in responders, but decreased in nonresponders.
MeSH term(s)	Brain ; Brain Neoplasms/radiotherapy ; Humans ; Patient Reported Outcome Measures ; Prospective Studies ; Quality of Life ; Referral and Consultation ; Telephone
Language	English
Publishing date	2022-04-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	1427361-5
ISSN	1557-7740 ; 1096-6218
ISSN (online)	1557-7740
ISSN	1096-6218
DOI	10.1089/jpm.2021.0533
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Zs.A 5440: Show issues

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Article ; Online: Comparison of Daily Online Plan Adaptation Strategies for a Cohort of Pancreatic Cancer Patients Treated with SBRT.

Magallon-Baro, Alba / Milder, Maaike T W / Granton, Patrick V / Nuyttens, Joost J / Hoogeman, Mischa S

International journal of radiation oncology, biology, physics

2021 Volume 111, Issue 1, Page(s) 208–219

Abstract: Purpose: To study the trade-offs of three online strategies to adapt treatment plans of patients with locally advanced pancreatic carcinoma (LAPC) treated using the CyberKnife with tumor tracking.: Methods and materials: A total of 35 planning ... ...

Abstract	Purpose: To study the trade-offs of three online strategies to adapt treatment plans of patients with locally advanced pancreatic carcinoma (LAPC) treated using the CyberKnife with tumor tracking. Methods and materials: A total of 35 planning computed tomography scans and 98 daily in-room computed tomography scans were collected from 35 patients with LAPC. Planned dose distributions, optimized with VOLO, were evaluated on manually contoured daily anatomies to collect daily doses. Three strategies were tested to adapt treatment plans: (1) unrestricted full replanning using a patient-specific plan template, (2) time-restricted replanning on organs at risk (OARs) within 3 cm from the planning target volume (PTV) structure, and (3) dose realignment optimization to stay within OAR constraints. Dose distributions resulting from each plan adaptation strategy were dosimetrically compared by means of gross tumor volume (GTV), PTV coverage, and OAR tolerances. Results: Planned doses did not result in dose-constraint violations for 28 of 98 daily anatomies. None of the suggested plan adaptation strategies improved planned doses significantly for this subset. For 70 of the 98 reported violations, the median (interquartile range) PTV coverage of the planned dose was 84% (76% to 86%). After plan adaptation, unrestricted replanning achieved clinically acceptable plans in 93% of these fractions, time-restricted replanning in 90%, and dose realignment in 74%, at median computational times of 8.5, 3, and 0.5 minutes. Over all 98 fractions, PTV coverage was reduced: -1% (-3% to 1%), -2% (-5% to 0%), and -2% (-8% to 0%) after each strategy, respectively. In 3 of 70 fractions, none of the suggested strategies achieved clinically acceptable OAR dose volumes. Conclusions: Unrestricted replanning was the most time-consuming method but reached the highest number of successfully adapted plans. Time-restricted replanning and dose realignment resulted in a high number of plans within dose constraints. Depending on the resources available, an adaptive strategy can be selected for each patient to address the specific anatomic challenges on the treatment day. The increase in the complexity of the strategy corresponds with an increasing number of successfully adapted plans.
MeSH term(s)	Aged ; Cohort Studies ; Female ; Humans ; Male ; Middle Aged ; Organs at Risk ; Pancreatic Neoplasms/radiotherapy ; Radiosurgery/methods ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted/methods
Language	English
Publishing date	2021-04-01
Publishing country	United States
Document type	Comparative Study ; 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.2021.03.050
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Zs.A 1218: Show issues

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Article ; Online: Induction chemotherapy followed by response evaluation and esophagectomy for advanced esophageal cancer.

van der Zijden, Charlène J / van der Sluis, Pieter C / Mostert, Bianca / Nuyttens, Joost J M E / Spaander, Manon C W / Toxopeus, Eelke L A / Valkema, Roelf / Beerepoot, Laurens V / van Halteren, Henk K / Lagarde, Sjoerd M / Wijnhoven, Bas P L

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology

2024 Volume 50, Issue 3, Page(s) 107968

Abstract: Introduction: Patients with limited metastatic/advanced esophageal cancer not amenable for neoadjuvant therapy plus surgery have a poor prognosis and often receive palliative care. Alternatively, induction chemotherapy with response evaluation can be ... ...

Abstract	Introduction: Patients with limited metastatic/advanced esophageal cancer not amenable for neoadjuvant therapy plus surgery have a poor prognosis and often receive palliative care. Alternatively, induction chemotherapy with response evaluation can be considered and in some patients surgery with curative intent may become feasible. The aim of this study was to evaluate the outcomes of patients treated with induction chemotherapy and to identify patient and/or tumor characteristics associated with survival. Material and methods: Patients with esophageal or junctional cancer who underwent induction chemotherapy between 2005 and 2021 were identified from an institutional database of a tertiary referral center. Response to therapy was assessed by ( Results: 238 patients were identified. The majority had esophageal adenocarcinoma (68.9 %) and were treated with a taxane/platinum-based chemotherapy (79.4 %). Response evaluation was performed in 233 patients and 154 of 238 patients (64.7 %) underwent surgical exploration. Resection was performed in 127 patients (53.4 %) resulting in a median and 5-year OS of 26.3 months (95 % CI 18.8-33.8) and 29.6 %, respectively. Presence of T4b (HR = 2.01, 95 % CI 1.02-3.92) and poorly differentiated tumor (HR = 1.45, 95 % CI 1.02-2.10) was associated with worse survival (p = 0.04). Conclusion: In carefully selected patients with advanced disease not amenable for standard curative treatment, induction chemotherapy followed by esophagectomy may result in a 5-year overall survival of approximately 30 %.
MeSH term(s)	Humans ; Induction Chemotherapy/methods ; Esophagectomy/methods ; Esophageal Neoplasms/surgery ; Esophageal Neoplasms/drug therapy ; Neoadjuvant Therapy/methods ; Adenocarcinoma/surgery ; Adenocarcinoma/drug therapy ; Survival Rate ; Retrospective Studies ; Neoplasm Staging
Language	English
Publishing date	2024-01-12
Publishing country	England
Document type	Journal Article
ZDB-ID	632519-1
ISSN	1532-2157 ; 0748-7983
ISSN (online)	1532-2157
ISSN	0748-7983
DOI	10.1016/j.ejso.2024.107968
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Zs.A 1149: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 549: Show issues

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