Publications by authors named "Dirk Van Gestel"

46 Publications

Recent advances in radiosensitivity determinants in melanoma.

Curr Opin Oncol 2022 Jan 10. Epub 2022 Jan 10.

Laboratory of Clinical and Experimental Oncology (LOCE), Institut Jules Bordet Department of Radiation Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.

Purpose Of Review: Radiotherapy has been proven to be useful but insufficient in melanoma management due to the intrinsic radioresistance of melanoma cells. Elucidation of the molecular mechanisms and pathways related to resistance/sensitivity to radiotherapy in melanoma is of paramount importance. In this review, we will summarize and discuss the recent 'discoveries' and advances in radiosensitivity determinants in melanoma.

Recent Findings: The different levels of radiosensitivity among the various melanoma tumors could be attributed to the DNA damage signaling and repair proteins, tumor microenvironment, hypoxia, cell metabolism, glutathione and redox balance, protein kinase signaling pathways as well as pigmentation and melanin content.

Summary: It is therapeutically important to elucidate the factors involved in radiation resistance/sensitivity of melanoma. More importantly, improving radiosensitivity may 'widen the clinical utility' in melanoma of this important therapeutic modality.
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http://dx.doi.org/10.1097/CCO.0000000000000818DOI Listing
January 2022

Humanized Mice as a Valuable Pre-Clinical Model for Cancer Immunotherapy Research.

Front Oncol 2021 18;11:784947. Epub 2021 Nov 18.

Department of Radiation Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.

Immunotherapy with checkpoint inhibitors opened new horizons in cancer treatment. Clinical trials for novel immunotherapies or unexplored combination regimens either need years of development or are simply impossible to perform like is the case in cancer patients with limited life expectancy. Thus, the need for preclinical models that rapidly and safely allow for a better understanding of underlying mechanisms, drug kinetics and toxicity leading to the selection of the best regimen to be translated into the clinic, is of high importance. Humanized mice that can bear both human immune system and human tumors, are increasingly used in recent preclinical immunotherapy studies and represent a remarkably unprecedented tool in this field. In this review, we describe, summarize, and discuss the recent advances of humanized mouse models used for cancer immunotherapy research and the challenges faced during their establishment. We also highlight the lack of preclinical studies using this model for radiotherapy-based research and argue that it can be a great asset to understand and answer many open questions around radiation therapy such as its presumed associated "abscopal effect".
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http://dx.doi.org/10.3389/fonc.2021.784947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8636317PMC
November 2021

Isotoxic high-dose stereotactic body radiotherapy integrated in a total multimodal neoadjuvant strategy for the treatment of localized pancreatic ductal adenocarcinoma.

Ther Adv Med Oncol 2021 19;13:17588359211045860. Epub 2021 Oct 19.

Department of Gastroenterology, Hepatology and Digestive Oncology, Hopital Erasme, Université Libre de Bruxelles, Brussels, Belgium.

Background: Our aim was to evaluate the feasibility and safety of isotoxic high-dose (iHD) stereotactic body radiation therapy (SBRT) in a total neoadjuvant sequence for the treatment of localized pancreatic adenocarcinoma.

Materials And Methods: Biopsy-proven borderline resectable/locally advanced pancreatic cancer (BR/LAPC) patients were included in this observational prospective analysis from August 2017 to April 2020 without excluding tumours showing a radiological direct gastrointestinal (GI) invasion. An induction chemotherapy by modified fluorouracil, irinotecan and oxaliplatin was performed for a median of six cycles. In case of non-progression, an isotoxic high-dose stereotactic body radiotherapy (iHD-SBRT) was delivered in 5 fractions followed by a surgical exploration. The primary endpoint was acute/late gastrointestinal grade ⩾3 toxicity. Secondary endpoints were overall survival (OS), progression-free survival (PFS) and local control (LC).

Results: A total of 39 consecutive patients (21 BR and 18 LAPC) were included: 34 patients (87.2%, 18 BR and 16 LAPC) completed the planned neoadjuvant sequence. After iHD-SBRT, 19 patients [55.9% overall, 13/18 BR (72.2%) and 6/16 LAPC (37.5%)] underwent an oncological resection among the 25 patients surgically explored (73.5%). The median follow up was 18.2 months. The rates of acute and late GI grade 3 toxicity were, respectively, 2.9% and 4.2%. The median OS and PFS from diagnosis were, respectively, 24.5 and 15.6 months. The resected patients had improved median OS and PFS in comparison with the non-resected patients (OS: 32.3 18.2 months,  = 0.02; PFS: 24.1 7.1 months,  < 0.001). There was no survival difference between the BR and LAPC patients. The 1-year LC from SBRT was 74.1% and the median locoregional PFS was not reached for both BR and LAPC patients.

Conclusions: iHD-SBRT displays an excellent toxicity profile, also for potentially high-risk patients with radiological direct GI invasion at diagnosis and can be easily integrated in a total neoadjuvant strategy. The oncological outcomes are promising and emphasise the need for further exploration of iHD-SBRT in phase II/III trials.
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http://dx.doi.org/10.1177/17588359211045860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8529314PMC
October 2021

Unintended dose to the lower axilla in adjuvant radiotherapy for breast cancer: Differences between tangential beam and VMAT.

Radiother Oncol 2021 11 11;164:282-288. Epub 2021 Oct 11.

Department of Radiation Oncology, Breast Working Group, Institut Jules Bordet, Université libre de Bruxelles, Brussels, Belgium. Electronic address:

Background And Purpose: To evaluate dosimetric differences in unintended dose to the lower axilla between 3D-standard (3DCRT), tangential beam forward intensity modulated radiotherapy (F-IMRT) and volumetric modulated arc therapy (VMAT). The objective is to evaluate whether results of clinical trials, such as the ACOSOG-Z011 trial, that evaluated omission of axillary clearance can be extrapolated towards more conformal techniques like VMAT.

Materials And Methods: Twenty-five consecutive patients treated with whole breast radiotherapy alone (WBRT) using a F-IMRT technique were identified. Three additional plans were created for every patient: one plan using a single 270° arc (VMAT 1x270°), another using two small ≤90° opposing arcs (VMAT 2x < 90°) and thirdly a 3DCRT plan without F-IMRT. Axillary levels I-II were contoured after the treatment plans were made.

Results: The volume of the axilla level I that was covered by the 50% isodose (V50%) was significantly higher for VMAT 2x < 90° (71.3 cm, 84% of structure volume, p < 0.001) and VMAT 1x270° (68.8 cm, 81%, p < 0.01) compared to 3DCRT (60.3 cm, 71%) and F-IMRT (60.8 cm, 72%). The V50% to the axilla level II, however, was low for all techniques: 12.3 cm (12%); 8.9 cm (9%); 4.3 cm (4%); 4.4 cm (4%) for VMAT 2x < 90°, VMAT 1x270°, 3DCRT, F-IMRT, respectively. For the higher doses (V90% and above), no clinically relevant differences were seen between the different modalities.

Conclusion: WBRT treatments with VMAT do not lead to a significant reduction of the unintended axillary dose in comparison with a tangential beam setup. Hence, concerning tumor control, VMAT can be applied to clinical situations similar to the Z0011 trial. The intermediate axillary dose is higher with VMAT, but the clinical consequence of this difference on toxicity is unknown.
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http://dx.doi.org/10.1016/j.radonc.2021.10.005DOI Listing
November 2021

Oligometastatic Disease Detection with Ga-PSMA-11 PET/CT in Hormone-Sensitive Prostate Cancer Patients (HSPC) with Biochemical Recurrence after Radical Prostatectomy: Predictive Factors and Clinical Impact.

Cancers (Basel) 2021 Oct 4;13(19). Epub 2021 Oct 4.

Department of Nuclear Medicine, Institut Jules Bordet, Université Libre de Bruxelles, 1000 Brussels, Belgium.

Metastasis-directed therapy (MDT) in oligometastatic prostate cancer has the potential of delaying the start of androgen deprivation therapy (ADT) and disease progression. We aimed to analyze the efficacy of PSMA-PET/CT in detecting oligometastatic disease (OMD), to look for predictive factors of OMD, and to evaluate the impact of PSMA-PET/CT findings on clinical management. We retrospectively analyzed a homogeneous population of 196 hormone-sensitive prostate cancer patients (HSPC), considered potential candidates for MDT, with a PSMA-PET/CT performed at biochemical recurrence (BCR) after radical prostatectomy (RP). Multivariable logistic regression analysis was performed based on several clinico-pathological factors. Changes in clinical management before and after PSMA-PET/CT were analyzed. The OMD detection rate was 44% for a total positivity rate of 60%. PSMA-PET/CT positivity was independently related to PSA (OR (95% CI), ) (1.7 (1.3-2.3), < 0.0001) and PSAdt (0.4 (0.2-0.8), = 0.013), and OMD detection was independently related to PSA (1.6 (1.2-2.2), = 0.001) and no previous salvage therapy (0.3 (0.1-0.9), = 0.038). A treatment change was observed in 58% of patients, mostly to perform MDT after OMD detection (60% of changes). This study showed that PSMA-PET/CT is an excellent imaging technique to detect OMD early in HSPC patients with BCR after RP, changing therapeutic management mostly into MDT.
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http://dx.doi.org/10.3390/cancers13194982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508549PMC
October 2021

Neo-CheckRay: radiation therapy and adenosine pathway blockade to increase benefit of immuno-chemotherapy in early stage luminal B breast cancer, a randomized phase II trial.

BMC Cancer 2021 Aug 6;21(1):899. Epub 2021 Aug 6.

Institut Jules Bordet, Université Libre de Bruxelles, Rue Héger Bordet 1, 1000, Brussels, Belgium.

Background: Residual breast cancer after neo-adjuvant chemotherapy (NACT) predicts disease outcome and is a surrogate for survival in aggressive breast cancer (BC) subtypes. Pathological complete response (pCR) rate, however, is lower for luminal B BC in comparison to the triple negative (TNBC) and HER2+ subtypes. The addition of immune checkpoint blockade (ICB) to NACT has the potential to increase pCR rate but is hampered by the lower immunogenicity of luminal B BC. Novel strategies are needed to stimulate the immune response and increase the response rate to ICB in luminal B BC.

Methods: The Neo-CheckRay trial is a randomized phase II trial investigating the impact of stereotactic body radiation therapy (SBRT) to the primary breast tumor in combination with an anti-CD73 (oleclumab) to increase response to anti PD-L1 (durvalumab) and NACT. The trial is designed as a three-arm study: NACT + SBRT +/- durvalumab +/- oleclumab. The result at surgery will be evaluated using the residual cancer burden (RCB) index as the primary endpoint. Six patients will be included in a safety run-in, followed by a randomized phase II trial that will include 136 evaluable patients in 3 arms. Inclusion is limited to luminal B breast cancers that are MammaPrint genomic high risk.

Discussion: combination of ICB with chemotherapy in luminal B BC might benefit from immune priming agents to increase the response rate. As none have been identified so far, this phase II trial will evaluate SBRT and oleclumab as potential immune priming candidates.

Trial Registration: trial registered on ClinicalTrials.gov ( NCT03875573 ) on March 14th, 2019.
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http://dx.doi.org/10.1186/s12885-021-08601-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343924PMC
August 2021

Prophylactic gastrostomy in locally advanced head and neck cancer: results of a national survey among radiation oncologists.

BMC Cancer 2021 Jun 2;21(1):656. Epub 2021 Jun 2.

Department of Radiation Oncology (Head and Neck Unit), Institut Jules Bordet, Université Libre de Bruxelles, 1 rue Héger Bordet - 1000 Bruxelles, Brussels, Belgium.

Background: Nutritional complications in patients with locally advanced head and neck cancer (LA-HNC) treated by concurrent chemoradiotherapy (CCRT) often lead to placement of a prophylactic gastrostomy (PG) tube, while indication lacks harmonization. Our aim was to explore the current PG tube utilization among Belgian radiation oncology centers.

Methods: A survey was distributed to all 24 Belgian Radiation oncology departments, with questions about the number of patient treated per year, whether the PG indication is discussed at the multidisciplinary board, placement technique, time of starting nutrition and removal, its impact on swallowing function and importance of clinical factors. For the latter Relative Importance and Discordance Indexes were calculated to describe the ranking and agreement.

Results: All 24 centers submitted the questionnaire. Twenty three treat more than 20 head and neck (HNC) patients per year, while four (1 in 21-50; 3 in 51-100) are not discussing the gastrostomy tube indication at the multidisciplinary board. For the latter, endoscopic placement (68%) is the dominant technique, followed by the radiologic (16%) and laparoscopic (16%) methods. Seventy-five percent start the enteral nutrition when clinically indicated, 17% immediately and 8% from the start of radiotherapy. Majority of specialists (19/24) keep the gastrostomy tube until the patient assume an adequate oral feeding. Fifteen centres are considering PG decrease swallowing function. Regarding factors and their importance in the decision for the PG, foreseen irradiated volume reached highest importance, followed by 'anatomical site', 'patients' choice' and 'postoperative versus definitive' and 'local expertise', with decreasing importance respectively. Disagreement indexes showed moderate variation.

Conclusions: The use of a PG tube for LAHNC patients treated by CCRT shows disparity at national level. Prospective studies are needed to ensure proper indication of this supportive measure.
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http://dx.doi.org/10.1186/s12885-021-08348-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171041PMC
June 2021

Preoperative and postoperative radiotherapy (RT) for non-small cell lung cancer: still an open question.

Transl Lung Cancer Res 2021 Apr;10(4):1950-1959

Department of Radiation Oncology, Institut Jules Bordet, Université Libre Bruxelles, Brussels, Belgium.

Preoperative and postoperative radiotherapy (PORT) with or without chemotherapy has been used in non-small cell lung cancer (NSCLC) for decades. Numerous trials have investigated the potential survival benefit of this strategy, but despite greater knowledge of the disease, considerable technological developments in imaging and radiotherapy, and significant progress in surgery, many questions remain unsolved. In this review, we summarize the current knowledge on this problem and discuss issues which still require elucidation.
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http://dx.doi.org/10.21037/tlcr-20-472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107767PMC
April 2021

Evaluation of the XVI dual registration tool for image-guided radiotherapy in prostate cancer.

Tech Innov Patient Support Radiat Oncol 2021 Jun 20;18:22-28. Epub 2021 Apr 20.

Radiation Oncology Department, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.

Purpose: To compare the reliability and the required time for two cone-beam CT (CBCT) registration methods for prostate irradiation (PI) and prostate bed irradiation (PBI).

Material And Methods: Two-hundred treatment fractions (in 10 PI and 10 PBI patients) were reanalyzed, using two CBCT registration methods: (1) a combination of an automated chamfer matching (CM) with manual matching (MM), and (2) the automated XVI dual registration tool (DRT). Bland-Altman 95% Limits of Agreement (LoA) were used to assess agreement with manual registration by Radiation Oncologists.

Results: All 95% LoA for CM + MM were ≤ 0.33 cm. For DRT, several 95% LoA were notably larger than the predefined clinical threshold of 0.3 cm: -0.47 to +0.25 cm (PI) and -0.36 to +0.23 cm (PBI) for the superior-inferior direction and -0.52 to +0.24 cm (PI) and -0.38 to +0.31 cm (PBI) for the anterior-posterior direction.For PI, the average time required was 33 s with CM + MM versus only 18 s with DRT ( = 0.002). For PBI, this was 13 versus 19 s, respectively ( = 0.16).

Conclusion: For PI, DRT was significantly faster than CM + MM, but the accuracy is insufficient to use without manual verification. Therefore, manual verification is still warranted, but could offset the time benefit. For PBI, the CM + MM method was faster and more accurate.
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http://dx.doi.org/10.1016/j.tipsro.2021.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093993PMC
June 2021

Checkpoint inhibition in combination with an immunoboost of external beam radiotherapy in solid tumors (CHEERS): study protocol for a phase 2, open-label, randomized controlled trial.

BMC Cancer 2021 May 7;21(1):514. Epub 2021 May 7.

Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium.

Background: While the introduction of checkpoint inhibitors (CPIs) as standard of care treatment for various tumor types has led to considerable improvements in clinical outcome, the majority of patients still fail to respond. Preclinical data suggest that stereotactic body radiotherapy (SBRT) could work synergistically with CPIs by acting as an in situ cancer vaccine, thus potentially increasing response rates and prolonging disease control. Though SBRT administered concurrently with CPIs has been shown to be safe, evidence of its efficacy from large randomized trials is still lacking. The aim of this multicenter randomized phase II trial is to assess whether SBRT administered concurrently with CPIs could prolong progression-free survival as compared to standard of care in patients with advanced solid tumors.

Methods/design: Ninety-eight patients with locally advanced or metastatic disease will be randomized in a 1:1 fashion to receive CPI treatment combined with SBRT (Arm A) or CPI monotherapy (Arm B). Randomization will be stratified according to tumor histology (melanoma, renal, urothelial, head and neck squamous cell or non-small cell lung carcinoma) and disease burden (≤ or > 3 cancer lesions). The recommended SBRT dose is 24Gy in 3 fractions, which will be administered to a maximum of 3 lesions and is to be completed prior to the second or third CPI cycle (depending on CPI treatment schedule). The study's primary endpoint is progression-free survival as per iRECIST. Secondary endpoints include overall survival, objective response, local control, quality of life and toxicity. Translational analyses will be performed using blood, fecal and tissue samples.

Discussion: The CHEERS trial will provide further insights into the clinical and immunological impact of SBRT when combined with CPIs in patients with advanced solid tumors. Furthermore, study results will inform the design of future immuno-radiotherapy trials.

Trial Registration: Clinicaltrials.gov identifier: NCT03511391 . Registered 17 April 2018.
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http://dx.doi.org/10.1186/s12885-021-08088-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106163PMC
May 2021

Assessment of cough in head and neck cancer patients at risk for dysphagia-An overview.

Cancer Rep (Hoboken) 2021 10 1;4(5):e1395. Epub 2021 May 1.

Department of Radiation Oncology, Head and Neck Unit, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.

Background: This literature review explores the terminology, the neurophysiology, and the assessment of cough in general, in the framework of dysphagia and regarding head and neck cancer patients at risk for dysphagia. In the dysphagic population, cough is currently assessed perceptually during a clinical swallowing evaluation or aerodynamically.

Recent Findings: Recent findings have shown intra and inter-rater disagreements regarding perceptual scoring of cough. Also, aerodynamic measurements are impractical in a routine bedside assessment. Coughing, however, is considered to be a clinically relevant sign of aspiration and dysphagia in head and cancer patients treated with concurrent chemoradiotherapy.

Conclusion: This article surveys the literature regarding the established cough assessment and stresses the need to implement innovative methods for assessing cough in head and neck cancer patients treated with concurrent chemoradiotherapy at risk for dysphagia.
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http://dx.doi.org/10.1002/cnr2.1395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551981PMC
October 2021

Split-VMAT technique to control the deep inspiration breath hold time for breast cancer radiotherapy.

Radiat Oncol 2021 Apr 20;16(1):77. Epub 2021 Apr 20.

Medical Physics Department, Institut Jules Bordet - Université Libre de Bruxelles, Brussels, Belgium.

Background: To improve split-VMAT technique by optimizing treatment delivery time for deep-inspiration breath hold (DIBH) radiotherapy in left-sided breast cancer patients, when automatic beam-interruption devices are not available.

Methods: Ten consecutive patients were treated with an eight partial arcs (8paVMAT) plan, standard of care in our center. A four partial arcs (4paVMAT) plan was also created and actual LINAC outputs were measured, to evaluate whether there was a dosimetric difference between both techniques and potential impact on the delivered dose. Subsequently, ten other patients were consecutively treated with a 4paVMAT plan to compare the actual treatment delivery time between both techniques. The prescribed dose was 40.05 Gy/15 fractions on the PTV breast (breast or thoracic wall), lymph nodes (LN) and intramammary lymph node chain (IMN). Treatment delivery time, PTVs coverage, conformity index (CI), organs at risk (OAR) dose, monitor units (MU), and gamma index were compared.

Results: Both split-VMAT techniques resulted in similar dose coverage for the PTV Breast and LN, and similar CI. For PTV IMN we observed a 5% increased coverage for the volume receiving ≥ 36 Gy with 4paVMAT, with an identical volume receiving ≥ 32 Gy. There was no difference for the OAR sparing, with the exception of the contralateral organs: there was a 0.6 Gy decrease for contralateral breast mean (p ≤ 0.01) and 1% decrease for the volume of right lung receiving ≥ 5 Gy (p = 0.024). Overall, these results indicate a modest clinical benefit of using 4paVMAT in comparison to 8paVMAT. An increase in the number of MU per arc was observed for the 4paVMAT technique, as expected, while the total number of MU remained comparable for both techniques. All the plans were measured with the Delta phantom and passed the gamma index criteria with no significant differences. Finally, the main difference was seen for the treatment delivery time: there was a significant decrease from 8.9 to 5.4 min for the 4paVMAT plans (p < .05).

Conclusions: This study is mainly of interest for centers who are implementing the DIBH technique without automatic beam-holding devices and who therefore may require to manually switch the beam on and off during breast DIBH treatment. Split-VMAT technique with 4 partial arcs significantly reduces the treatment delivery time compared to 8 partial arcs, without compromising the target coverage and the OAR sparing. The technique decreases the number of breath holds per fraction, resulting in a shorter treatment session.
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http://dx.doi.org/10.1186/s13014-021-01800-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056647PMC
April 2021

Impact of the COVID-19 Pandemic on Patients and Staff in Radiation Oncology Departments in Belgium: A National Survey.

Front Oncol 2021 19;11:654086. Epub 2021 Mar 19.

Department of Human Structure and Repair, Ghent University, Ghent, Belgium.

COVID-19 reached Belgium in February and quickly became a major public health challenge. It is of importance to evaluate the actual impact of COVID-19 on patients and staff in Belgian radiotherapy departments (RTDs). This was evaluated through a weekly national survey sent to departments measuring key factors that were affected by the pandemic. The Belgian SocieTy for Radiation Oncology (BeSTRO) together with the Belgian College for physicians in Radiation Oncology invited all 26 RTD to participate in a survey that started on March 2nd and was re- submitted weekly for 4 months to assess variations in time. The survey focused on: (1) the COVID-19 status of patients and staff; (2) the management of clinically suspected COVID patients and COVID positive patients; (3) the impact of COVID-19 on RTD activities; (4) its impact in radiotherapy indications and fractionation schemes. Seventy-three percent of 26 RTDs completed the first survey and 57% responded to all weekly surveys. In the RTD staff, 24 members were COVID-positive of whom 67% were RTTs. Over the study period, the number of patients treated dropped by a maximum of 18.8% when compared to March 2nd. In 32.3% of COVID-positive and 54% of COVID suspected patients, treatment was continued without any interruptions. Radiotherapy indications were adapted within the 1st weeks of the survey in 47.4% of RTD, especially for urological and breast tumors. Fractionation schemes were changed in 68.4% of RTD, mainly for urological, breast, gastro-intestinal, and lung tumors. Between March and June 2020, the COVID-19 pandemic resulted in an important decrease in treatment activity in RTD in Belgium (18.8%). The COVID-19 infection status of patients influenced the continuity of the radiotherapy schedule. Changes in indications and fractionation schedules of radiotherapy were rapidly incorporated in the different RTD.
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http://dx.doi.org/10.3389/fonc.2021.654086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017334PMC
March 2021

Editorial: Quality Assessment Across Disciplines in Head and Neck Cancer Treatment.

Front Oncol 2021 19;11:636622. Epub 2021 Feb 19.

Department of Radiation Oncology, Institute Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.

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http://dx.doi.org/10.3389/fonc.2021.636622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934614PMC
February 2021

Successful treatment of synchronous chemoresistant pulmonary metastasis from pleomorphic rhabdomyosarcoma with stereotaxic body radiation therapy: A case report and a review of the literature.

Cancer Treat Res Commun 2021 11;26:100282. Epub 2020 Dec 11.

Institut Jules Bordet-Université Libre de Bruxelles, Department of Radiation-Oncology, Brussels, Belgium.

Background: Rhabdomyosarcoma (RMS) is a highly malignant soft tissue sarcoma (STS), usually of adults, displaying skeletal muscle differentiation. STS principally metastasize to the lungs with more than 50% of metastatic patients presenting with isolated pulmonary metastasis. Paradoxically, the majority of drugs prescribed to treat RMS are associated with multidrug resistance.

Case Report: We report the case of a 53 year-old patient who developed three synchronous chemoresistant lung metastasis from pleomorphic RMS. Considering the poor prognosis, the patient's preference and the chemoresistance of her lung metastasis, we decided to perform two consecutive stereotactic body radiotherapy (SBRT) on two of these three lesions.

Discussion: Initially, the patient was referred to our institute with a painful mass in the anterior part of the left thigh increasing in volume for 3 months. Biopsy revealed a high-grade pleomorphic RMS. The cancer being staged IB, she had neoadjuvant radiotherapy. After complete surgical excision, pathology examination revealed a 6 cm Grade II pleomorphic RMS, with clear margins. Six months later, she developed three synchronous lung metastases. She got 4 courses of doxorubicin-ifosfamide which were poorly supported. After two courses, a heterogeneous (morphological and metabolic) response was observed, hence SBRT was delivered with a Biologically Equivalent Dose (α/β10)> 100 Gray on the two more chemoresistant lesions. This SBRT was very well tolerated, no side effects were reported. The patient remained alive and achieved a complete response of these three metastases, which sustains after more than 3 years.

Conclusion: Early recognition and proper management of these oligometastatic patients may lead to motivating results in a poor prognosis disease.
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http://dx.doi.org/10.1016/j.ctarc.2020.100282DOI Listing
December 2021

Meta-Analysis on Induction Chemotherapy in Locally Advanced Nasopharyngeal Carcinoma.

Oncologist 2021 01 1;26(1):e130-e141. Epub 2020 Oct 1.

Department of Radiation-Oncology, Institut Jules Bordet-Université Libre de Bruxelles, Brussels, Belgium.

Purpose: Concurrent chemo radiotherapy (CCRT) has been the standard of care in locally advanced nasopharyngeal carcinoma (LA-NPC) for many years. The role of induction chemotherapy (ICT) has always been controversial. This systematic review and meta-analysis investigates the value of adding ICT to CCRT in LA-NPC.

Materials And Methods: Two reviewers independently assessed the eligibility of randomized controlled trials (RCTs) comparing ICT followed by CCRT versus CCRT alone, including treatment-naive adult patients with histologically proven nonmetastatic LA-NPC.

Results: Eight RCTs with in total 2,384 randomized patients, of whom 69% had N2-N3 disease, were selected. ICT was the allocated treatment in 1,200 patients, of whom 1,161 actually received this. Treatment compliance varied, with a median rate of 92% (range, 86%-100%) of patients receiving all cycles of ICT. The percentage of patients completing radiotherapy was 96% and 95% [(Combined Risk difference(CRD)= 0.004; 95% Confidence Interval (CI) -0.001-0.01; p = 0.14)] in the ICT group and CCRT group, respectively, whereas chemotherapy during radiotherapy could be completed in only 28% of the ICT group versus 61% in the CCRT group (CRD, -0.243; 95% CI, -0.403 to -0.083; p = .003). Grade 3-4 acute toxicity was mostly hematologic during the ICT phase (496 events vs. 191 nonhematologic) and was predominant in the ICT group (1,596 events vs. 1,073 in the CCRT alone group) during the CCRT. Adding ICT to CCRT provided a significant benefit in overall survival (hazard ratio [HR], 0.680; 95% CI, 0.511-0.905; p = .001) and progression-free survival (HR, 0.657; 95% CI, 0.568-0.760; p < .001).

Conclusion: Although ICT followed by CCRT is associated with more acute toxicity and a lower compliance of the chemotherapy during the CCRT phase, this association resulted in a clinically meaningful survival benefit. ICT should be considered as a standard option in patients with LA-NPC, but further study on optimal patient selection for this treatment is warranted.

Implications For Practice: Locally advanced nasopharyngeal carcinoma (LA-NPC) is a relatively common disease in some parts of the world, with a rather poor prognosis due to its high metastatic potential. The role of induction chemotherapy (ICT) has always been controversial. This meta-analysis found that ICT followed by concurrent chemoradiotherapy (CCRT) in LA-NPC is associated with a significant clinical improvement in both overall survival and progression-free survival compared with CCRT alone. ICT should be considered as a standard option in patients with LA-NPC.
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http://dx.doi.org/10.1002/ONCO.13520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794190PMC
January 2021

Novel strategies using modern radiotherapy to improve pancreatic cancer outcomes: toward a new standard?

Ther Adv Med Oncol 2020 7;12:1758835920936093. Epub 2020 Jul 7.

Department of Gastroenterology, Hepatology and Digestive Oncology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive solid tumours with an estimated 5-year overall survival rate of 7% for all stages combined. In this highly resistant disease that is located in the vicinity of many radiosensitive organs, the role of radiotherapy (RT) and indications for its use in this setting have been debated for a long time and are still under investigation. Although a survival benefit has yet to be clearly demonstrated for RT, it is the only technique, other than surgery, that has been demonstrated to lead to local control improvement. The adjuvant approach is now strongly challenged by neoadjuvant treatments that could spare patients with rapidly progressive systemic disease from unnecessary surgery and may increase free margin (R0) resection rates for those eligible for surgery. Recently developed dose-escalated RT treatments, designed either to maintain full-dose chemotherapy or to deliver a high biologically effective dose, particularly to areas of contact between the tumour and blood vessels, such as hypofractionated ablative RT (HFA-RT) or stereotactic body RT (SBRT), are progressively changing the treatment landscape. These modern strategies are currently being tested in prospective clinical trials with encouraging preliminary results, paving the way for more effective treatment combinations using novel targeted therapies. This review summarizes the current literature regarding the use of RT for the treatment of primary PDAC, describes the limitations of conventional RT, and discusses the emerging role of dose-escalated RT and heavy-particle RT.
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http://dx.doi.org/10.1177/1758835920936093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343368PMC
July 2020

Brachytherapy in Belgium in 2018. A national survey of the brachytherapy study group of the Belgian SocieTy for Radiotherapy and Oncology (BeSTRO).

Radiother Oncol 2020 09 15;150:245-252. Epub 2020 Jul 15.

Department of Radiation Oncology, Institut Jules Bordet - Université Libre de Bruxelles, Brussels, Belgium.

Purpose: To explore the current practices patterns and evaluate the actual brachytherapy (BT) resources in Belgium.

Material And Methods: In 2019, the Brachytherapy Study Group proposed to conduct a survey on behalf of the Belgian SocieTy of Radiation Oncology (BeSTRO) in order to identify current BT practice patterns. An electronic questionnaire was sent to all primary radiotherapy centers in Belgium. This questionnaire was based on the questionnaire that was used by the Italian Association of Radiation Oncology (AIRO) in 2016, asking for: (a) General information on the Radiation Oncology Centre; (b) BT equipment and human resources; (c) BT procedures; (d) BT assessment (number of patients treated annually, treated sites, and different modalities of treatments).

Results: All 24 radiation oncology centers (100% response rate) answered the questionnaire and gave also information on the performance of brachytherapy in their (eventual) satellite centers. Eighteen (18) BT afterloader units were installed and operational in 2018. Thirteen centers mentioned a prostate seed implant program, one center a prostate and eye plaque program and one center only an eye plaque program. Less than 50% of centers have the infrastructure to offer the full-range of BT in their own department. In 2018, 1486 patients received a BT-treatment, 28% of them were treated by prostate seed implant, 8% were treated by eye-(seed) BT and 64% by high dose rate (HDR)/pulsed dose rate (PDR) BT. Forty-five percent of HDR/PDR patients were treated by vaginal dome BT, 22% by intra-uterine BT, 11% by skin BT, 10% by breast BT (almost exclusively in one centre), 8% for benign pathology (keloid) and the remaining 4% were treated for prostate (as a boost or as salvage in one centre), anal, penile, lung or oesophageal cancer.

Conclusions: Belgian radiotherapy departments often perform BT only in a (highly) selected group of pathologies, resulting in a limited number of patients treated by this technique despite the sufficient availability of BT equipment. Modern indications are often not covered, hence patients do not have regular access to recognized treatment options, possibly leading to inferior oncological outcome. BeSTRO will use the results of this survey to stimulate improvements in training, awareness, education, implementation, collaboration and cooperation in the field of brachytherapy.
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http://dx.doi.org/10.1016/j.radonc.2020.07.010DOI Listing
September 2020

Follow-Up of Head and Neck Cancer Survivors: Tipping the Balance of Intensity.

Front Oncol 2020 6;10:688. Epub 2020 May 6.

Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.

The traditional concept of post-treatment surveillance in head and neck cancer patients relies on examinations directed at early detection of disease recurrence and/or second primary tumors. They are usually provided by ear, nose and throat specialists with complementary input from radiation oncologists and medical oncologists. Emerging evidence underscores the importance of monitoring and effective management of late adverse events. One of the major drawbacks is a lack of prospective controlled data. As a result, local institutional policies differ, and practice recommendations are subject to continuing debate. Due to the economic burden and impact on emotional comfort of patients, intensity and content of follow-up visits are a particularly conflicting topic. According to the current evidence-based medicine, follow-up of head and neck cancer patients does not prolong survival but can improve quality of life. Therefore, an approach giving priority to a multidisciplinary care involving a speech and swallowing expert, dietician, dentist, and psychologist may indeed be more relevant. Moreover, on a case-by-case basis, some patients need more frequent consultations supplemented by imaging modalities. Human papillomavirus positive oropharyngeal cancer tends to develop late failures at distant sites, and asymptomatic oligometastatic disease, especially in the lungs, can be successfully salvaged by local ablation, either surgically or by radiation. The deep structures of the skull base related to the nasopharynx are inaccessible to routine clinical examination, advocating periodic imaging supplemented by nasofibroscopy as indicated. Anamnesis of heavy smoking justifies annual low-dose computed tomography screening of the thorax and intensive smoking cessation counseling. Finally, some cancer survivors feel more comfortable with regular imaging, and their voice should be taken into consideration. Future development of surveillance strategies will depend on several variables including identification of reliable predictive factors to select those who could derive the most benefit from follow-up visits, the availability of long-term follow-up data, the results of the first randomized trials, resource allocation patterns, infrastructure density, and the therapeutic landscape of locally advanced and recurrent and/or metastatic disease, which is rapidly changing with the advent of immune checkpoint inhibitors and better utilization of local approaches.
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http://dx.doi.org/10.3389/fonc.2020.00688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218054PMC
May 2020

Radiotherapy Quality Assurance for Head and Neck Squamous Cell Carcinoma.

Front Oncol 2020 12;10:282. Epub 2020 Mar 12.

Departments of Radiation Oncology, Charité University Medicine Berlin, Berlin, Germany.

The impact of radiotherapy (RT) quality assurance (QA) has been demonstrated by numerous studies and is particularly important for head and neck cancer (HNC) treatment due to the complexity of RT target volumes in this region and the multiple adjacent organs at risk. The RT planning process includes many critical steps including interpretation of diagnostic imaging, image fusion, target volume delineation (tumor, lymph nodes, and organs at risk), and planning. Each step has become highly complex, and precise and rigorous QA throughout the planning process is essential. The ultimate aim is to precisely deliver radiation dose to the target, maximizing the tumor dose and minimizing the dose to surrounding organs at risk, in order to improve the therapeutic index. It is imperative that RT QA programs should systematically control all aspects of the RT planning pathway and include regular end-to-end tests and external audits. However, comprehensive QA should not be limited to RT and should, where possible, also be implemented for surgery, systemic therapy, pathology, as well as other aspects involved in the interdisciplinary treatment of HNC.
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http://dx.doi.org/10.3389/fonc.2020.00282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081058PMC
March 2020

Clinical outcome and toxicity after simultaneous integrated boost IMRT in head and neck squamous cell cancer patients.

Oral Oncol 2019 11 3;98:132-140. Epub 2019 Oct 3.

Department of Radiotherapy-Oncology, Institut Jules Bordet - Université Libre de Bruxelles (U.L.B.), Brussels, Belgium. Electronic address:

Introduction: A simultaneous integrated boost (SIB) intensity modulated radiotherapy (IMRT) in patients with head and neck squamous cell carcinoma (HNSCC) allows to irradiate different target volumes to different dose levels within a single treatment session without increasing the toxicity.

Aim: To analyze the outcome and toxicity of patients treated by definitive or postoperative SIB IMRT for HNSCC.

Material And Methods: 106 patients with HNSCC of the oral cavity (OC), oropharynx (OP), larynx (L) and hypopharynx (HP), consecutively treated at our cancer center between 3/2012 and 3/2014 were retrospectively analyzed. The prescribed SIB IMRT doses were in the postoperative setting (group A) 60-66 Gy and 53 Gy in 30-33 fractions for PTV high risk and PTV elective, respectively; and 70 Gy and 56 Gy in 35 fractions for PTV high risk and PTV elective, respectively when given as primary treatment (group B). Toxicity was consistently graded according to RTOG/EORTC scale.

Results: Median follow-up duration was 31 months. Thirty (28%) patients were postoperatively irradiated (group A) and 76 (72%) patients received definitive IMRT (group B). At 3 years, loco-regional control, distant control and overall survival were 78%, 78%, 57% and 64%, 76%, 52% in the postoperative (group A) and the definitive SIB IMRT group (group B), respectively. The observed acute grade 3 toxicities were dysphagia (44%), oral and/or oropharyngeal mucositis (40%) and dermatitis (21%). Late toxicity was predominantly clinically significant xerostomia (42%), dysgeusia (23%) and dysphagia (8%).

Conclusion: SIB IMRT is feasible, safe and effective in the treatment of HNSCC patients.
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http://dx.doi.org/10.1016/j.oraloncology.2019.09.012DOI Listing
November 2019

Prognostic impact of glioblastoma stem cell markers OLIG2 and CCND2.

Cancer Med 2020 02 30;9(3):1069-1078. Epub 2019 Sep 30.

Department of Pathology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.

Aims: Glioblastoma (GBM) is the most common and lethal malignant brain tumor in adults. Glioma stem cells (GSCs) are implicated in this poor prognosis and in radio(chemo-)resistance. We have previously demonstrated that among potentially highly specific GSC markers oligodendrocyte lineage transcription factor 2 (OLIG2) appears to be the most specific and cyclin D2 (CCND2) the only one related to cell cycle regulation. The purpose of this work was to investigate the clinical significance and the evolution of OLIG2 and CCND2 protein expression in GBM.

Methods And Results: Immunohistochemical expression analysis of Olig2 and Ccnd2 was carried out on a cohort of human paired GBM samples comparing initial resections with local recurrent tumors after radiation therapy (RT) alone or radio-chemotherapy with temozolomide (RT-TMZ). Uni- and multivariate logistic regression analysis revealed that significant risk factors predicting early mortality (<12 months) are: subtotal surgery for recurrence, time to recurrence <6 months, Ccnd2 nuclear expression at initial surgery ≥30%, and Olig2 nuclear expression <30% at second surgery after RT alone and RT-TMZ.

Conclusions: We demonstrated that patients for whom nuclear expression of Olig2 becomes low (<30%) after adjuvant treatments have a significantly shorter time to recurrence and survival reflecting most probably a proneural to mesenchymal transition of the GSCs population. We also highlighted the fact that at initial surgery, high nuclear expression (≥30%) of CCND2, a G1/S regulator specific of GSCs, has a prognostic value and is associated with early mortality (<12 months).
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http://dx.doi.org/10.1002/cam4.2592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997071PMC
February 2020

The Benefit of Reactivating p53 under MAPK Inhibition on the Efficacy of Radiotherapy in Melanoma.

Cancers (Basel) 2019 Aug 1;11(8). Epub 2019 Aug 1.

Department of Radiation Oncology, Institut Jules Bordet, Université libre de Bruxelles, 1000 Brussels, Belgium.

Radiotherapy (RT) in patients with melanoma historically showed suboptimal results, because the disease is often radioresistant due to various mechanisms such as scavenging free radicals by thiols, pigmentary machinery, or enhanced DNA repair. However, radiotherapy has been utilized as adjuvant therapy after the complete excision of primary melanoma and lymph nodes to reduce the rate of nodal recurrences in high-risk patients. The resistance of melanoma cells to radiotherapy may also be in relation with the constitutive activation of the MAPK pathway and/or with the inactivation of p53 observed in about 90% of melanomas. In this study, we aimed to assess the potential benefit of adding RT to BRAF-mutated melanoma cells under a combined p53 reactivation and MAPK inhibition in vitro and in a preclinical animal model. We found that the combination of BRAF inhibition (vemurafenib, which completely shuts down the MAPK pathway), together with p53 reactivation (PRIMA-1) significantly enhanced the radiosensitivity of BRAF-mutant melanoma cells. This was accompanied by an increase in both p53 expression and activity. Of note, we found that radiation alone markedly promoted both ERK and AKT phosphorylation, thus contributing to radioresistance. The combination of vemurafenib and PRIMA-1 caused the inactivation of both MAPK kinase and PI3K/AKT pathways. Furthermore, when combined with radiotherapy, it was able to significantly enhance melanoma cell radiosensitivity. Interestingly, in nude mice bearing melanoma xenografts, the latter triple combination had not only a synergistic effect on tumor growth inhibition, but also a potent control on tumor regrowth in all animals after finishing the triple combination therapy. RT alone had only a weak effect. In conclusion, we provide a basis for a strategy that may overcome the radioresistance of BRAF-mutated melanoma cells to radiotherapy. Whether this will translate into a rational to use radiotherapy in the curative setting in BRAF-mutated melanoma patients deserves consideration.
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http://dx.doi.org/10.3390/cancers11081093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721382PMC
August 2019

Ossifying Fibromyxoid Tumor with Spinal Cord Compression and Epiduritis.

J Belg Soc Radiol 2019 Feb 28;103(1):18. Epub 2019 Feb 28.

Department of Medical Imaging, CHU Saint-Pierre, Université Libre de Bruxelles, Brussels, BE.

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http://dx.doi.org/10.5334/jbsr.1606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403422PMC
February 2019

Low-Dose vs. High-Dose Cisplatin: Lessons Learned From 59 Chemoradiotherapy Trials in Head and Neck Cancer.

Front Oncol 2019 21;9:86. Epub 2019 Feb 21.

Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.

In locally advanced squamous cell carcinomas of the head and neck (LA-SCCHN), concurrent chemoradiotherapy is an integral part of multimodality management both in the adjuvant and in the definitive settings. Although de-intensification strategies have been propelled to the forefront of clinical research in human papillomavirus (HPV) positive oropharyngeal cancer, three cycles of 100 mg/m cisplatin given every 3 weeks concurrently with conventionally fractionated external beam radiotherapy represent a cost-effective and globally accessible treatment option for the majority of LA-SCCHN cases. Based on four large randomized trials, this regimen has become the non-surgical standard of care for cisplatin-eligible patients. Nevertheless, the outcomes in terms of efficacy, toxicity, and compliance have been rather disappointing. Therefore, there is an unmet need to find a better alternative. With limited support from randomized trials, weekly low-dose cisplatin regimens have replaced the standard high-dose schedule at some institutions. Four prospective trials exploring radiotherapy with and without weekly low-dose cisplatin have been published. Two of them were conducted in the 1980s, one of which had a negative outcome, the third study provided insufficient information on toxicity, and the fourth trial had to be prematurely terminated due to poor accrual. Moreover, the findings of two phase III trials comparing the two concurrent cisplatin regimens favored the high-dose protocol. We performed a composite meta-analysis of 59 prospective trials enrolling a total of 5,582 patients. The primary endpoint was overall survival. Reflecting different radiotherapy fractionation schemes and treatment intents, three meta-analyses were carried out, one for postoperative conventional chemoradiotherapy, one for definitive conventional chemoradiotherapy, and one for definitive altered fractionation chemoradiotherapy. In the former two settings, both high- and low-dose regimens yielded similar survival outcomes, thus, the primary objective was not met. When given concurrently with altered fractionation radiotherapy, patients treated with high-dose cisplatin had significantly longer overall survival than those who received low-dose cisplatin. In this article we provide a synthetic view of the results, discuss the issue of cumulative dose, compare two vs. three cycles of high-dose cisplatin, and present our three-step recommendations for use of the current standard of care, high-dose cisplatin, in clinical practice.
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http://dx.doi.org/10.3389/fonc.2019.00086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394212PMC
February 2019

Evolution of self-perceived swallowing function, tongue strength and swallow-related quality of life during radiotherapy in head and neck cancer patients.

Head Neck 2019 07 14;41(7):2197-2207. Epub 2019 Feb 14.

Department of Otolaryngology and Head and Neck Surgery - Rehabilitation Center for Communication Disorders, Antwerp University Hospital, Antwerp, Belgium.

Background: Radiation-associated-dysphagia is a serious side effect of radiotherapy (RT) for head and neck cancer (HNC).

Methods: Seventy-six patients had a weekly prospective follow-up from baseline until one week post-RT. Combined mixed model analysis (n = 43) determined the evolution of self-perceived swallowing function, isometric tongue strength (MIP), tongue strength (TS) during swallowing (Pswal), and quality of life (QoL) in these patients during RT.

Results: Swallowing deteriorated from the third week on, resulting in an increase of tube dependency from 10% at baseline toward 31% post-RT. Both MIP and Pswal are reduced, with anterior MIP decreasing in 29% of patients and posterior MIP in 17%. Pswal decreases for saliva and a bolus swallow. All QoL subscales except "sleep" were affected during RT.

Conclusions: Self-perceived swallowing function, TS and QoL decrease during RT for HNC. Current findings highlight the need for early monitoring of these parameters.
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http://dx.doi.org/10.1002/hed.25684DOI Listing
July 2019

Immune checkpoint blockade for organ transplant patients with advanced cancer: how far can we go?

Curr Opin Oncol 2019 03;31(2):54-64

Department of Dermatology.

Purpose Of Review: Checkpoint inhibitors (CPIs) provide impressive response rates among immunocompetent patients with various solid tumors. So far, organ transplant recipients have been excluded from clinical studies due to the putative risk of allograft rejection however 48 cases of liver and renal transplant patients treated with CPI were already described in literature.

Recent Findings: Here we discuss 19 cases of liver and 29 cases of renal transplant patients who received CPI for advanced cancer. Disease control rate [stable disease, complete response (CR) and partial response (PR) together] was 35% (21% for liver and 45% for kidney transplant patients). Graft rejection was seen in 37% of liver and 45% and kidney transplant patients. Significantly, our analysis shows that an 'ideal' response occurs in 21% of all patients (antitumor response accompanied with durable graft tolerance).

Summary: We believe that transplant patients can be treated with CPI in a controlled setting and for well informed patients. To obtain a durable antitumor immune response while avoiding rejection, to be able to adjust immunosuppression and to have the opportunity to develop biomarkers for tumor response and transplant rejection, these patients should be treated according to a clinical care path or a prospective clinical trial.
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http://dx.doi.org/10.1097/CCO.0000000000000505DOI Listing
March 2019

Dose-response in choroidal melanoma.

Radiother Oncol 2018 06 18;127(3):374-378. Epub 2018 Apr 18.

Department of Radiation Oncology, University Hospital of Leuven (UZ Leuven), Leuven, Belgium.

Purpose: In choroidal melanoma the radiation threshold dose for local control remains largely unknown. The present study examined a group of patients that received a wide range of minimum tumor dose in order to investigate a dose-response relationship. A literature review is performed to compare our results with available evidence in brachytherapy and charged particle external beam radiotherapy.

Materials And Methods: A retrospective study was conducted on all choroidal melanomas treated with Strontium-90 (Sr-90) at the University Hospital of Leuven between 1983 and 2012. Local failure was defined as primary endpoint and was estimated according to the competing risk method.

Results: In 135 patients, the minimum tumor dose (Dmin) ranged from 0 Gy to 287 Gy (median: 27.6 Gy). Multivariable analysis revealed Dmin ≥ 65 Gy (p = 0.04; HR = 0.09) and tumor distant from the optic disc (p < 0.001, HR = 0.09) to be independent variables favoring local control. The scleral dose, the tumor diameter and tumor height did not significantly affect local failure in multivariate analysis.

Conclusion: This is the first study to examine a group of patients treated with a Dmin ranging from 0 Gy to >250 Gy. Treatment with a Dmin of 65 Gy is necessary to achieve durable tumor response. The dose-response data provided by our study could be used for the design of future trials examining the ideal dose for the treatment of choroidal melanoma with brachytherapy or charged particle external beam radiotherapy.
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http://dx.doi.org/10.1016/j.radonc.2018.03.019DOI Listing
June 2018

A feasibility study on adaptive F-FDG-PET-guided radiotherapy for recurrent and second primary head and neck cancer in the previously irradiated territory.

Strahlenther Onkol 2018 08 19;194(8):727-736. Epub 2018 Mar 19.

Department of Radiation Oncology, Ghent University Hospital, C. Heymanslaan 10, 9000, Ghent, Belgium.

Purpose: To evaluate feasibility, disease control, survival, and toxicity after adaptive F-fluorodeoxyglucose (FDG) positron emisson tomography (PET) guided radiotherapy in patients with recurrent and second primary head and neck squamous cell carcinoma.

Methods: A prospective trial investigated the feasibility of adaptive intensity modulated radiotherapy (IMRT) ± concomitant cetuximab in 10 patients. The primary endpoint was achieving a 2-year survival free of grade >3 toxicity in ≥30% of patients. Three treatment plans based on 3 PET/CT scans were consecutively delivered in 6 weeks. The range of dose painting was 66.0-85.0 Gy in the dose-painted tumoral volumes in 30 fractions.

Results: Two-year locoregional and distant control rates were 38 and 76%, respectively. Overall and disease-free survival at 2 years was 20%. No grade 4 or 5 acute toxicity was observed in any of the patients, except for arterial mucosal hemorrhage in 1 patient. Three months after radiotherapy, grade 4 dysphagia and mucosal wound healing problems were observed in 1/7 and 1/6 of patients, respectively. Grade 5 toxicity (fatal bleeding) was seen in 2 patients, at 3.8 and 4.1 months of follow-up. Data on 2‑year toxicity could only be assessed in 1 of the 2 surviving patients, in whom grade 4 mucosal wound healing problems were observed; no other grade >3 toxicity was observed. In this respect, a 30% 2‑year survival free of grade >3 toxicity will not be achieved.

Conclusions: Adaptive PET-guided reirradiation is feasible. However, due to slow accrual and treatment results that seemed inconsistent with achieving the primary endpoint, the trial was stopped early.
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http://dx.doi.org/10.1007/s00066-018-1293-3DOI Listing
August 2018

Unusual presentation of a hepatocellular carcinoma as a potential late side effect of radiotherapy in a patient treated for Wilms tumor in childhood.

World J Surg Oncol 2018 Mar 7;16(1):48. Epub 2018 Mar 7.

Service de Chirurgie, Institut Jules Bordet, Université Libre de Bruxelles, 121 Boulevard de Waterloo, 1000, Brussels, Belgium.

Background: The development of a second primary tumor is a potential late side effect of radiotherapy. Particularly, an increased risk of secondary cancers, mostly of digestive or breast origin, has been observed in patients treated with high-dose radiotherapy for Wilms tumor (WT) in childhood. However, hepatocellular carcinoma (HCC) has been very rarely described as a potentially radiotherapy-induced tumor. We describe the case of a patient with an aggressive HCC 50 years after the treatment of a WT.

Case Presentation: A 49-year old man, treated at the age of 6 weeks for a right WT by a right nephrectomy and adjuvant radiotherapy, presented with a right abdominal mass. Imaging demonstrated a 100-mm tumor invading the inferior segment of the right liver, the right colon and the right psoas muscle. The patient had no previous history of liver disease, nor of alcohol consumption, and hepatitis serologies were negatives. Biopsy demonstrated a poorly differentiated tumor of unknown origin. A panel of tumor markers was negative. Explorative surgery has been performed allowing en bloc R0 tumor resection, including resection of segments VI and VII of the liver, right hemicolectomy and resection of the anterior sheet of the right psoas muscle. Pathological examination revealed a poorly differentiated HCC. No signs of cirrhosis or chronic liver disease were observed in the non-tumor liver. Twenty weeks after surgery, the patient developed a multifocal tumor recurrence that was treated with intra-arterial Yttrium radioembolization.

Conclusion: In this case, the absence of risk factors for HCC, such as cirrhosis, viral hepatitis and chronic liver disease, highly suggests the development of HCC to be related to previous high-dose radiation therapy given for a right WT to a field involving the inferior part of the liver. This observation shows radiotherapy to/near the liver, particularly in childhood, to be a potential risk factor for HCC, stressing the need for a long-term specific follow-up in patients irradiated in childhood.
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http://dx.doi.org/10.1186/s12957-018-1346-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842595PMC
March 2018
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