Publications by authors named "Alex De Caluwe"

10 Publications

  • Page 1 of 1

Delineation guidelines for the lymphatic target volumes in 'prone crawl' radiotherapy treatment position for breast cancer patients.

Sci Rep 2021 11 18;11(1):22529. Epub 2021 Nov 18.

Department of Human Structure and Repair, Ghent University, C. Heymanslaan 10, Radiotherapy park, entrance 98, 9000, Ghent, Belgium.

Our recently developed prone crawl position (PCP) for radiotherapy of breast cancer patients with lymphatic involvement showed promising preliminary data and it is being optimized for clinical use. An important aspect in this process is making new, position specific delineation guidelines to ensure delineation (for treatment planning) is uniform across different centers. The existing ESTRO and PROCAB guidelines for supine position (SP) were adapted for PCP. Nine volunteers were MRI scanned in both SP and PCP. Lymph node regions were delineated in SP using the existing ESTRO and PROCAB guidelines and were then translated to PCP, based on the observed changes in reference structure position. Nine PCP patient CT scans were used to verify if the new reference structures were consistently identified and easily applicable on different patient CT scans. Based on these data, a team of specialists in anatomy, CT- and MRI radiology and radiation oncology postulated the final guidelines. By taking the ESTRO and PROCAB guidelines for SP into account and by using a relatively big number of datasets, these new PCP specific guidelines incorporate anatomical variability between patients. The guidelines are easily and consistently applicable, even for people with limited previous experience with delineations in PCP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-01841-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602302PMC
November 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radonc.2021.10.005DOI Listing
November 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-021-08601-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343924PMC
August 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13014-021-01800-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056647PMC
April 2021

PRIMMO study protocol: a phase II study combining PD-1 blockade, radiation and immunomodulation to tackle cervical and uterine cancer.

BMC Cancer 2019 May 28;19(1):506. Epub 2019 May 28.

Division of Medical Oncology, UZ Gent, Ghent, Belgium.

Background: Immunotherapeutic approaches have revolutionized oncological practice but are less evaluated in gynecological malignancies. PD-1/PD-L1 blockade in gynecological cancers showed objective responses in 13-17% of patients. This could be due to immunosuppressive effects exerted by gynecological tumors on the microenvironment and an altered tumor vasculature. In other malignancies, combining checkpoint blockade with radiation delivers benefit that is believed to be due to the abscopal effect. Addition of immune modulation agents has also shown to enhance immune checkpoint blockade efficacy. Therefore we designed a regimen consisting of PD-1 blockade combined with radiation, and different immune/environmental-targeting compounds: repurposed drugs, metronomic chemotherapy and a food supplement. We hypothesize that these will synergistically modulate the tumor microenvironment and induce and sustain an anti-tumor immune response, resulting in tumor regression.

Methods: PRIMMO is a multi-center, open-label, non-randomized, 3-cohort phase 2 study with safety run-in in patients with recurrent/refractory cervical carcinoma, endometrial carcinoma or uterine sarcoma. Treatment consists of daily intake of vitamin D, lansoprazole, aspirin, cyclophosphamide and curcumin, starting 2 weeks before the first pembrolizumab dose. Pembrolizumab is administered 3-weekly for a total of 6 cycles. Radiation (3 × 8 Gy) is given on days 1, 3 and 5 of the first pembrolizumab dose. The safety run-in consists of 6 patients. In total, 18 and 25 evaluable patients for cervical and endometrial carcinoma respectively are foreseen to enroll. No sample size is determined for uterine sarcoma due to its rarity. The primary objective is objective response rate at week 26 according to immune-related response criteria. Secondary objectives include safety, objective response rate at week 26 according to RECIST v1.1, best overall response, progression-free survival, overall survival and quality of life. Exploratory, translational research aims to evaluate immune biomarkers, extracellular vesicles, cell death biomarkers and the gut microbiome.

Discussion: In this study, a combination of PD-1 blockade, radiation and immune/environmental-targeting compounds is tested, aiming to tackle the tumor microenvironment and induce anti-tumor immunity. Translational research is performed to discover biomarkers related to the mode of action of the combination.

Trial Registration: EU Clinical Trials Register: EudraCT 2016-001569-97 , registered on 19-6-2017. Clinicaltrials.gov: NCT03192059 , registered on 19-6-2017.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-019-5676-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537207PMC
May 2019

Radiation therapy for young women with early breast cancer: Current state of the art.

Crit Rev Oncol Hematol 2019 May 2;137:143-153. Epub 2019 Mar 2.

Radiation Oncology Unit, Oncology Department, Azienda Ospedaliero Universitaria Careggi, Florence, Italy; Department of Biomedical, Experimental, and Clinical Sciences "M. Serio", University of Florence, Florence, Italy.

A diagnosis of breast cancer at a young age, defined per guidelines as ≤ 40 years, represents a challenging situation requiring additional attention by the treating physicians including radiation oncologists and surgeons involved in the local treatment of these tumors. The present review aims at providing updated evidence on the state of the art about the available techniques and indications for radiation therapy in patients with early breast cancer, specifically focusing on young women. In addition, future perspectives including the ongoing trials and the potential impact of combined approaches with systemic therapies (such as immunotherapy) are reviewed. Major conclusions from this overview are that young women affected by invasive breast cancer seem to receive the greatest benefit from the boost on the tumor bed. Most young patients affected by ductal carcinoma in situ should receive postoperative whole breast irradiation (WBI). When regional node irradiation is considered, young age should be considered as a high-risk factor. Partial breast irradiation is not suitable for young patients and should be recommended within the context of a clinical trial. Importantly, robust data have already supported the efficacy and safety of hypofractionated-WBI schedules that should now replace standard fractionated-WBI as gold standard for all patients irrespective of their age. Finally, organs-at-risk sparing systems as strategy for prevention of radiation-related long-term toxicities should be strongly considered for these patients. Considering the lack of inclusion of young patients in several published trials as well as in some of the ongoing ones, robust evidence to counsel young breast cancer patients on the optimal radiation therapy approach is still lacking. Further studies and ad hoc subgroup analyses in this specific patient population are strongly warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.critrevonc.2019.02.014DOI Listing
May 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radonc.2018.03.019DOI Listing
June 2018

The incidence of symptomatic brain metastases from extra-pulmonary small cell carcinoma: Is there a role for prophylactic cranial irradiation in a clinically relevant population cohort?

Radiother Oncol 2017 07 26;124(1):31-37. Epub 2017 Jun 26.

Department of Radiation Oncology, BC Cancer Agency - Abbotsford Center, Canada.

Background And Purpose: To examine the incidence and outcomes of patients with brain metastases from extra-pulmonary small cell carcinoma (EPSCC) and assess the indication for prophylactic cranial irradiation (PCI).

Materials And Methods: A Provincial cancer registry was used to conduct a retrospective, population-based study of patients diagnosed with EPSCC between January 1997 and December 2011. The primary end point was the incidence of brain metastases. The secondary endpoint was overall survival. A "PCI Eligible" cohort was defined to provide an estimation of the incidence of brain metastases in clinically relevant patients.

Results: In 287 patients, the primary sites were 21% gastrointestinal, 34% genito-urinary, 14% gynecologic, 5% head/neck and 25% unknown primary. Thirty-five (12.5%) patients had brain metastases: 12 (4.2%) at initial diagnosis and 23 (8%) later in the disease course. In PCI Eligible patients, the 3-year cumulative incidence of new brain metastases was 5.5% for M0 stage disease and 26.3% for M1 disease. There was no significant difference in the incidence of brain metastases between primary sites.

Conclusions: The incidence of brain metastases in patients with EPSCC is comparatively low, even in a cohort of patients that were suitable for PCI. Based on our analysis, we cannot recommend PCI for patients with EPSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radonc.2017.06.005DOI Listing
July 2017

Miliary metastases are associated with epidermal growth factor receptor mutations in non-small cell lung cancer: a population-based study.

Acta Oncol 2017 Sep 19;56(9):1175-1180. Epub 2017 May 19.

c Jules Bordet Institute , Brussels , Belgium.

Background: Miliary metastases are characterized by metastatic nodules that are diffuse, innumerable and small. The purpose of this study was to examine the incidence, prognostic significance and impact of epidermal growth factor receptor (EGFR) mutations for miliary metastases from non-small cell lung cancer (NSCLC).

Material And Methods: Patients were identified from a Provincial cancer registry (British Columbia, Canada) for the period 2010-2012. Inclusion criteria were stage IV NSCLC at presentation and conclusive EGFR mutation testing. Miliary metastases were defined by subjective and objective radiographic criteria. The primary endpoint was the incidence of miliary lung, brain and liver metastases. Secondary endpoints were survival and the prognostic implication for each site of miliary metastases.

Results: For 543 patients, the total number of brain, lung and liver metastases were 165 (30.4%), 290 (53.4%) and 67 (12.3%), respectively. The EGFR mutation positive (EGFR+) subgroup had a significantly higher 3-year cumulative incidence of miliary brain (4.1 vs. 0.5%, p = .015) and miliary lung (11.6 vs. 3.3%, p < .001) metastases compared to EGFR wild type (WT). A greater proportion of metastases from EGFR + cancers were miliary for brain (8.5 vs. 1.7%, p = .035) and lung (18.9 vs. 6.9%, p = .003) sites. Only non-miliary brain (HR = 1.45) and liver (HR = 1.70) metastases predicted for poor overall survival.

Conclusions: Mutations in EGFR were associated with a higher rate of miliary brain and lung metastases. The presence of miliary metastases did not predict for poor overall survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/0284186X.2017.1328128DOI Listing
September 2017

EGFR mutation status on brain metastases from non-small cell lung cancer.

Lung Cancer 2016 06 6;96:101-7. Epub 2016 Apr 6.

Vancouver Centre, BC Cancer Agency, British Columbia, Canada.

Objectives: The purpose of this study was to examine the impact of EGFR mutations on the incidence of brain metastases in patients with advanced non-small cell lung cancer (NSCLC).

Materials And Methods: A retrospective, population-based study was conducted using a provincial cancer registry to identify patients with metastatic NSCLC. Patients with diagnostic EGFR mutation testing were divided into EGFR mutation positive (EGFR+) and EGFR wild type (WT) cohorts. The primary endpoint was the incidence of brain metastases. Cumulative incidence curves were estimated using the competing risk method. The secondary endpoint was overall survival.

Results: For 543 patients there were 121 EGFR+ and 422 EGFR WT. The cumulative incidence of brain metastases was 39.2% for EGFR+ patients compared to 28.2% for EGFR WT (p=0.038; HR 1.4). In multivariate analysis, younger age and EGFR+ status were significant factors for developing brain metastases. The median survival for the EGFR+ and EGFR WT cohorts were 22.4 and 7.9 months (p<0.001), respectively. In multivariate analysis, poor performance status and brain metastases were factors significant for worse survival.

Conclusions: There is a higher incidence of brain metastases for patients with EGFR+ metastatic NSCLC, even when adjusted for differences in survival, compared to EGFR WT. For patients with and without brain metastases, survival prognosis with stage IV NSCLC is much longer with EGFR+ disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lungcan.2016.04.004DOI Listing
June 2016
-->