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Due to the general aging population and the fashion trend of sun exposure, non-melanoma skin cancer (NMSC) is rising. The management of NMSC is difficult and necessitates a multidisciplinary team (i.e., pathologists, dermatologists,... more
Due to the general aging population and the fashion trend of sun exposure, non-melanoma skin cancer (NMSC) is rising. The management of NMSC is difficult and necessitates a multidisciplinary team (i.e., pathologists, dermatologists, medical oncologists, surgeons, and radiation oncologists). When surgery is not an option or will cause unacceptably functional morbidity, radiation therapy (RT) may be a preferable tissue-preserving option. Whether used alone or in conjunction with other treatments, RT has been shown to be quite effective in terms of cosmetic results and local control. Contact hypofractionated RT, brachytherapy, and electronic brachytherapy are all promising new treatments. However, rigorous, randomized trials are missing, explaining the disparity in dose, fractionation, and technique recommendations. Therefore, it is essential that interdisciplinary teams better understand RT modalities, benefits, and drawbacks. Our review will provide the role and indications for RT in...
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Highlights • Radiation Therapists specialised in image-guided radiation therapy (RTT spIGRT) experience their role positiveltly.• The RTT spIGRT role is perceived to have a positive influence on radiotherapy treatment delivery.• A legal... more
Highlights • Radiation Therapists specialised in image-guided radiation therapy (RTT spIGRT) experience their role positiveltly.• The RTT spIGRT role is perceived to have a positive influence on radiotherapy treatment delivery.• A legal framework to provide formal RTT training and continuous education in order to increase radiotherapy treatment quality is of utmost importance.
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Quality assessment is indispensable in all areas of cancer care, and that is certainly true for head and neck cancer. The increased complexity of diagnosis and the multimodal and multiprofessional treatment and expanding (financial)... more
Quality assessment is indispensable in all areas of cancer care, and that is certainly true for head and neck cancer. The increased complexity of diagnosis and the multimodal and multiprofessional treatment and expanding (financial) burden to the health care system leads to concern whether new knowledge is effectively transferred to all patients. Moreover, there are major geographical differences in accessibility of radiotherapy equipment and anti-cancer drugs around the globe. Impaired quality of care results in compromised quality of life or sometimes even in impaired survival. Quality assurance must cover the entire patient care process from the diagnosis to the therapeutic decision and for that the multidisciplinary team (MDT) meetings are playing a crucial role.
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BACKGROUNDAND 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).... more
BACKGROUNDAND 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° (71.3cm3, 84% of structure volume, p<0.001) and VMAT 1x270° (68.8 cm3, 81%, p<0.01) compared to 3DCRT (60.3cm3, 71%) and F-IMRT (60.8cm3, 72%). The V50% to the axilla level II, however, was low for all techniques: 12.3cm3 (12%); 8.9cm3 (9%); 4.3cm3 (4%); 4.4cm3 (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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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... more
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 ...
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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... more
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-1Met) significantly en...
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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... more
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 mod...
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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.... more
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...
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Cough efficacy is considered a reliable predictor of the aspiration risk in head and neck cancer patients with radiation-associated dysphagia. Currently, coughing is assessed perceptually or aerodynamically. The goal of our research is to... more
Cough efficacy is considered a reliable predictor of the aspiration risk in head and neck cancer patients with radiation-associated dysphagia. Currently, coughing is assessed perceptually or aerodynamically. The goal of our research is to develop methods of acoustic cough analysis. In this study, we examined in a healthy population the acoustical differences between three protective maneuvers: voluntary cough, voluntary throat clearing, and induced reflexive cough. Forty healthy participants were included in this study. Voluntary cough, voluntary throat clearing, and reflexive cough samples were recorded and analyzed acoustically. Temporal acoustic features were the following: the slope and curvature of the amplitude contour, as well as the average, slope, and curvature of the sample entropy and kurtosis contours of the recorded signal. Spectral features were the relative energy in the frequency bands (0–400 Hz, 400–800 Hz, 800–1600 Hz, 1600 Hz-3200 Hz, > 3200 Hz) as well as the ...
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Cough efficacy is considered a reliable predictor of the aspiration risk in head and neck cancer patients with radiation-associated dysphagia. Currently, coughing is assessed perceptually or aerodynamically. The goal of our research is to... more
Cough efficacy is considered a reliable predictor of the aspiration risk in head and neck cancer patients with radiation-associated dysphagia. Currently, coughing is assessed perceptually or aerodynamically. The goal of our research is to develop methods of acoustic cough analysis. In this study, we examined in a healthy population the acoustical differences between three protective maneuvers: voluntary cough, voluntary throat clearing, and induced reflexive cough. Forty healthy participants were included in this study. Voluntary cough, voluntary throat clearing, and reflexive cough samples were recorded and analyzed acoustically. Temporal acoustic features were the following: the slope and curvature of the amplitude contour, as well as the average, slope, and curvature of the sample entropy and kurtosis contours of the recorded signal. Spectral features were the relative energy in the frequency bands (0–400 Hz, 400–800 Hz, 800–1600 Hz, 1600 Hz-3200 Hz, > 3200 Hz) as well as the ...
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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... more
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 ...
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Over the last years, the oligometastatic disease state has gained more and more interest, and randomized trials are now suggesting an added value of stereotactic radiotherapy on all macroscopic disease in oligometastatic patients; but... more
Over the last years, the oligometastatic disease state has gained more and more interest, and randomized trials are now suggesting an added value of stereotactic radiotherapy on all macroscopic disease in oligometastatic patients; but what barriers could impede widespread disease in some patients? In this review, we first discuss the concept of oligometastatic disease and some examples of clinical evidence. We then explore the route to dissemination: the hurdles a tumoral clone has to overtake before it can produce efficient and widespread dissemination. The spectrum theory argues that the range of metastatic patterns encountered in the clinic is the consequence of gradually obtained metastatic abilities of the tumor cells. Tumor clones can obtain these capabilities by Darwinian evolution, hence early in their genetic progression tumors might produce only a limited number of metastases. We illustrate selective dissemination by discussing organ tropism, the preference of different ca...
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Supplemental material, sj-docx-1-tam-10.1177_17588359211045860 for Isotoxic high-dose stereotactic body radiotherapy integrated in a total multimodal neoadjuvant strategy for the treatment of localized pancreatic ductal adenocarcinoma by... more
Supplemental material, sj-docx-1-tam-10.1177_17588359211045860 for Isotoxic high-dose stereotactic body radiotherapy integrated in a total multimodal neoadjuvant strategy for the treatment of localized pancreatic ductal adenocarcinoma by Christelle Bouchart, Jean-Luc Engelholm, Jean Closset, Julie Navez, Patrizia Loi, Yeter Gökburun, Thierry De Grez, Laura Mans, Alain Hendlisz, Maria Antonietta Bali, Pierre Eisendrath, Dirk Van Gestel, Matthieu Hein, Luigi Moretti and Jean-Luc Van Laethem in Therapeutic Advances in Medical Oncology
info:eu-repo/semantics/nonPublishe
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Additional file 1.
TP53 mutation is one of the most frequent genetic alterations in head and neck squamous cell carcinoma (HNSCC) and results in an accumulation of p53 protein in tumor cells. This makes p53 an attractive target to improve HNSCC therapy by... more
TP53 mutation is one of the most frequent genetic alterations in head and neck squamous cell carcinoma (HNSCC) and results in an accumulation of p53 protein in tumor cells. This makes p53 an attractive target to improve HNSCC therapy by restoring the tumor suppressor activity of this protein. Therapeutic strategies targeting p53 in HNSCC can be divided into three categories related to three subtypes encompassing WT p53, mutated p53 and HPV-positive HNSCC. First, compounds targeting degradation or direct inhibition of WT p53, such as PM2, RITA, nutlin-3 and CH1iB, achieve p53 reactivation by affecting p53 inhibitors such as MDM2 and MDMX/4 or by preventing the breakdown of p53 by inhibiting the proteasomal complex. Second, compounds that directly affect mutated p53 by binding it and restoring the WT conformation and transcriptional activity (PRIMA-1, APR-246, COTI-2, CP-31398). Third, treatments that specifically affect HPV+ cancer cells by targeting the viral enzymes E6/E7 which are...
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Background: The treatment of nasopharyngeal carcinoma (NPC) consists of radiotherapy alone (stage I) or radiotherapy concomitant with chemotherapy (stage II-V). Acute side effects management forms a major challenge for practitioners.... more
Background: The treatment of nasopharyngeal carcinoma (NPC) consists of radiotherapy alone (stage I) or radiotherapy concomitant with chemotherapy (stage II-V). Acute side effects management forms a major challenge for practitioners. Substantial literature is available from endemic areas, whereas data from Europe is scarce. This study examines clinical characteristics, therapeutic results, acute and late side effects of patients treated at the Jules Bordet Institute. Materials and Methods: Twenty-two consecutive non-metastatic NPC patients treated between May 2012 and September 2015 were retrospectively analyzed. All patients were treated by Intensity Modulated Radiation Therapy (IMRT) with or without chemotherapy (CT). Results: Thirteen patients have North-African ancestry while nine are of European origin. Seventy-three percent had a non-keratinizing carcinoma and 90% had an advanced stage disease (III-IVb). Ninety-five percent of the patients received concomitant CT. After a medi...
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Purpose: Radiotherapy (RT) has evolved substantially since its first clinical use in 1896. Most recently, the introduction of the computed tomography (cT) scan in the 1980s launched 2 decades of technologic (r)evolution. in this article... more
Purpose: Radiotherapy (RT) has evolved substantially since its first clinical use in 1896. Most recently, the introduction of the computed tomography (cT) scan in the 1980s launched 2 decades of technologic (r)evolution. in this article we will give an overview of the recent technical advances in external beam RT for head and neck cancer (hNc). Discussion: in hNc, intensity-modulated RT (iMRT) has become standard of care as it has shown superiority over 3d conformal RT in terms of prevention of xerostomia. other treatment options are fractionated stereotactic RT as a boost and the use of particle therapy with its interesting ballistic capacities. carbon ions will be mainly used for radio-resistant cancers because of the supplementary higher biologic effect. adaptive RT is promising but needs much more evolution before it can be optimally used. all these new techniques require a high level of image guidance in order to reach their maximal capacities. Rigorous quality assurance of all...
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... more
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% Confidenc...
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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... more
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 consecu...
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BackgroundThis 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... more
BackgroundThis 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 findingsRecent 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.ConclusionThis 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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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... more
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), p) (1.7 (1.3–2.3), p < 0.0001) and PSAdt (0.4 (0.2–0....
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Introduction: Regions within solid tumors often experience mild to severe oxygen deprivation, associated with resistance to chemotherapy and irradiation. The aim of this study was to evaluate the radiosensitizing effect of gemcitabine and... more
Introduction: Regions within solid tumors often experience mild to severe oxygen deprivation, associated with resistance to chemotherapy and irradiation. The aim of this study was to evaluate the radiosensitizing effect of gemcitabine and its main metabolite dFdU under normal versus reduced oxygen conditions and to determine whether hypoxia-inducible factor 1 (HIF-1) is involved in the radiosensitizing mechanism. Materials & methods: The clonogenic assay was performed in three isogenic MDA-MB-231 breast cancer cell lines differing in HIF-1alpha proficiency (24h 0-8 nM gemcitabine or 0-4 microM dFdU, 0-8 Gy irradiation). Validation of the transfection with dominant negative HIF-1alpha was done by western blot and by assessment of HIF-1alpha activity. The relative expression of 84 genes related to the hypoxia signaling pathway was characterized by human hypoxia signaling pathway PCR array. Using radiosensitizing conditions, cells were collected for cell cycle analysis. Results: HIF-1 ...