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1.
Acta Oncol ; 59(8): 895-903, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32319845

RESUMO

Background: Proximal esophageal cancer (EC) is commonly treated with definitive chemoradiation (CRT). The radiation dose and type of chemotherapy backbone are still under debate. The objective of this study was to compare the treatment outcomes of contemporary CRT regimens.Material and Methods: In this retrospective observational cohort study, we included patients with locally advanced squamous cell cancer of the proximal esophagus, from 11 centers in the Netherlands, treated with definitive CRT between 2004 and 2014. Each center had a preferential CRT regimen, based on cisplatin (Cis) or carboplatin-paclitaxel (CP) combined with low (≤50.4 Gy) or high (>50.4 Gy) dose radiotherapy (RT). Differences in overall survival (OS) between CRT regimens were assessed using a fully adjusted Cox proportional hazards and propensity score (PS) weighted model. Safety profiles were compared using a multilevel logistic regression model.Results: Two hundred patients were included. Fifty-four, 39, 95, and 12 patients were treated with Cis-low-dose RT, Cis-high-dose RT, CP-low-dose RT, and CP-high-dose RT, respectively. Median follow-up was 62.6 months (95% CI: 47.9-77.2 months). Median OS (21.9 months; 95% CI: 16.9-27.0 months) was comparable between treatment groups (logrank p = .88), confirmed in the fully adjusted and PS weighted model (p > .05). Grades 3-5 acute adverse events were less frequent in patients treated with CP-low-dose RT versus Cis-high-dose RT (OR 3.78; 95% CI: 1.31-10.87; p = .01). The occurrence of grades 3-5 late toxicities was not different between treatment groups.Conclusion: Our study was unable to demonstrate a difference in OS between the CRT regimens, probably related to the relatively small sample size. Based on the superior safety profile, carboplatin and paclitaxel-based CRT regimens are preferred in patients with locally advanced proximal EC.

2.
J Cachexia Sarcopenia Muscle ; 11(1): 145-159, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31536685

RESUMO

BACKGROUND: Chemoradiation or bioradiation treatment (CRT/BRT) of locally advanced head and neck squamous cell carcinoma (LAHNSCC) comes with high toxicity rates, often leading to temporary tube feeding (TF) dependency. Cachexia is a common problem in LAHNSCC. Yet changes in body composition and muscle weakness during CRT/BRT are underexplored. Strong evidence on the effect of TF on body composition during treatment is lacking. The aim of this cohort study was to assess (i) the relationship of fat-free mass index (FFMI) and handgrip strength (HGS) with CRT/BRT toxicity and outcome, (ii) body composition in patients treated with chemoradiation (cisplatin) vs. bioradiation (cetuximab), and (iii) the effect of the current TF regime on body composition and muscle strength. METHODS: Locally advanced head and neck squamous cell carcinoma patients treated with CRT/BRT between January 2013 and December 2016 were included (n = 137). Baseline measurements of body composition (bioelectrical impedance analysis) and HGS were performed. Toxicity grades (Common Terminology Criteria for Adverse Events) were scored. In a subset of 69 patients, weight loss, body composition, and HGS were additionally assessed during and after CRT/BRT. TF was initiated according to the Dutch guidelines for malnutrition. RESULTS: In this cohort (68% male, mean age 59 ± 8 years), the incidence of baseline muscle wasting, defined as FFMI < P10 , was 29%. Muscle wasting was present in 23 of 100 (23%) chemoradiation patients and 17 of 37 (46%) bioradiation patients (P = 0.009). Muscle-wasted patients required more unplanned hospitalizations during CRT (P = 0.035). In the chemoradiation subset, dose-limiting toxicity was significantly higher in wasted vs. non-wasted patients (57% vs. 25%, P = 0.004). Median follow-up was 32 months. Multivariate Cox regression analysis identified muscle wasting as independent unfavourable prognostic factor for overall survival [hazard ratio 2.1 (95% CI 1.1-4.1), P = 0.022] and cisplatin as favourable prognostic factor [hazard ratio 0.3 (95% CI 0.2-0.6), P = 0.001]. Weight and HGS significantly decreased during CRT/BRT, -3.7 ± 3.5 kg (P < 0.001) and -3.1 ± 6.0 kg (P < 0.001), respectively. Sixty-four per cent of the patients required TF 21 days (range 0-59) after CRT/BRT initiation. Total weight loss during CRT/BRT was significantly (P = 0.007) higher in the total oral diet group (5.5 ± 3.7 kg) compared with the TF group (3.0 ± 3.2 kg). Loss of FFM and HGS was similar in both groups. CONCLUSIONS: In LAHNSCC patients undergoing CRT/BRT, FFMI < P10 is an unfavourable prognostic factor for overall survival, treatment toxicity, and tolerance. Patients experience significant weight and FFM loss during treatment. Current TF regime attenuates weight loss but does not overcome loss of muscle mass and function during therapy. Future interventions should consider nutritional intake and additional strategies specifically targeting metabolism, loss of muscle mass, and function.

3.
J Clin Oncol ; 38(1): 81-99, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31743054

RESUMO

PURPOSE: Precision medicine trials in glioblastoma (GBM) are often conducted at tumor recurrence. However, second surgeries for recurrent GBM are not routinely performed, and therefore, molecular data for trial inclusion are predominantly derived from the primary sample. This study aims to establish whether molecular targets change during tumor progression and, if so, whether this affects precision medicine trial design. MATERIALS AND METHODS: We collected 186 pairs of primary-recurrent GBM samples from patients receiving chemoradiotherapy with temozolomide and sequenced approximately 300 cancer genes. MGMT, TERT, and EGFRvIII status was individually determined. RESULTS: The molecular profile of our cohort was identical to that of other GBM cohorts (IDH wild-type [WT], 95%; EGFR amplified, approximately 50%), indicating that patients amenable to second surgery do not represent a specific molecular subtype. Molecular events in IDH WT GBMs were stable in approximately 80% of events, but changes in mutation status were observed for all examined genes (range, approximately 90% and 60% for TERT and EGFR mutations, respectively), and such changes strongly affected targeted trial size and design. A similar pattern of GBM driver instability was observed within MGMT promoter-methylated tumors. MGMT promoter methylation status remained prognostic at tumor recurrence. The observation that hypermutation at GBM recurrence was rare (8%) and not correlated with outcome was relevant for immunotherapy-based treatments. CONCLUSION: This large cohort of matched primary and recurrent IDH WT tumors establishes the frequency of GBM driver instability after chemoradiotherapy with temozolomide. This allows per gene or pathway calculation of trial size at tumor recurrence, using molecular data of the primary tumor only. We also identify genes for which repeat surgery is necessary because of low mutation retention rate.

4.
Clin Nutr ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31839429

RESUMO

BACKGROUND & AIMS: Chemoradiation and bioradiation (CRT/BRT) for locally advanced head and neck squamous cell carcinoma (LAHNSCC) often comes with high toxicity rates, interfering with oral intake and leading to temporary tube feeding (TF) dependency. High-quality scientific evidence for indicators of prophylactic gastrostomy insertion is not available. The aim of this retrospective cohort study was to develop a prediction model to identify patients who need prophylactic gastrostomy insertion, defined as the expected use of TF for at least four weeks. METHODS: Four-hundred-fifty LAHNSCC patients receiving CRT/BRT with curative intent between 2013 and 2016 were included in the study. Primary outcome was TF-dependency for four weeks or longer. Patient, tumor, and treatment characteristics were extracted from the medical records and their effects on the use of TF were analyzed using univariable and multivariable analysis. The prediction model was internally validated using bootstrapping techniques. RESULTS: Sixty-five percent (294/450 patients) required TF for four weeks or longer. Variables included in the model were: body mass index and adjusted diet at start of CRT/BRT, percentage weight change at baseline, World Health Organization performance status, tumor subsite, TNM-classification, CRT/BRT, mean radiation dose on the contralateral submandibular and parotid gland. The corrected Area Under the Curve after internal validation was 72.3%, indicating good discriminative properties of the prediction model. CONCLUSIONS: We developed and internally validated a prediction model that is intended to estimate TF-dependency for at least four weeks in LAHNSCC patients treated with CRT/BRT. This model can be used as a tool to support personalized decision making on prophylactic gastrostomy insertion.

5.
Eur J Cancer ; 113: 32-40, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30965213

RESUMO

BACKGROUND: Platinum-based chemoradiotherapy for locally advanced head and neck cancer (LAHNC) induces a high rate of acute toxicity, including dysphagia and aspiration pneumonia. We hypothesised that prophylactic antibiotics can prevent pneumonia and hospitalisations and can be cost-effective. PATIENT AND METHODS: In this multicentre randomised trial, patients with LAHNC treated with chemoradiotherapy received prophylactic amoxicillin/clavulanic acid from day 29 after the start of treatment until 14 days after completion of chemoradiotherapy or standard care without prophylaxis. The primary objective was to observe a reduction in pneumonias. Secondary objectives were to evaluate the hospitalisation rate, adverse events, costs and health-related quality of life. RESULTS: One hundred six patients were included; of which, 95 were randomised: 48 patients were allocated to the standard group and 47 patients to the prophylaxis group. A pneumonia during chemoradiotherapy and follow-up until 3.5 months was observed in 22 (45.8%) of 48 patients in the standard group and in 22 (46.8%) of 47 patients in the prophylaxis group (p = 0.54). Hospitalisation rate was significantly higher in the standard group versus the prophylaxis group, 19 of 48 pts (39.6%) versus 9 of 47 pts (19.1%), respectively (p = 0.03). Significantly more episodes with fever of any grade were observed in the standard group (29.2% vs 10.2%, p = 0.028). A significant difference in costs was found, with an average reduction of €1425 per patient in favour of the prophylaxis group. CONCLUSION: Although prophylactic antibiotics during chemoradiotherapy for patients with LAHNC did not reduce the incidence of pneumonias, it did reduce hospitalisation rates and episodes with fever significantly and consequently tended to be cost-effective.

6.
Acta Oncol ; 58(1): 57-65, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30474448

RESUMO

BACKGROUND AND PURPOSE: Patients with low-grade glioma (LGG) have a prolonged survival expectancy due to better discriminative tumor classification and multimodal treatment. Consequently, long-term treatment toxicity gains importance. Contemporary radiotherapy techniques such as intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), tomotherapy (TOMO) and intensity-modulated proton therapy (IMPT) enable high-dose irradiation of the target but they differ regarding delivered dose to organs at risk (OARs). The aim of this comparative in silico study was to determine these dosimetric differences in delivered doses. MATERIAL AND METHODS: Imaging datasets of 25 LGG patients having undergone postoperative radiotherapy were included. For each of these patients, in silico treatment plans to a total dose of 50.4 Gy to the target volume were generated for the four treatment modalities investigated (i.e., IMRT, VMAT, TOMO, IMPT). Resulting treatment plans were analyzed regarding dose to target and surrounding OARs comparing IMRT, TOMO and IMPT to VMAT. RESULTS: In total, 100 treatment plans (four per patient) were analyzed. Compared to VMAT, the IMPT mean dose (Dmean) for nine out of 10 (90%) OARs was statistically significantly (p < .02) reduced, for TOMO this was true in 3/10 (30%) patients and for 1/10 (10%) patients for IMRT. IMPT was the prime modality reducing dose to the OARs followed by TOMO. DISCUSSION: The low dose volume to the majority of OARs was significantly reduced when using IMPT compared to VMAT. Whether this will lead to a significant reduction in neurocognitive decline and improved quality of life is to be determined in carefully designed future clinical trials.


Assuntos
Neoplasias Encefálicas/radioterapia , Glioma/radioterapia , Órgãos em Risco/efeitos da radiação , Terapia com Prótons/métodos , Humanos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada
7.
J Geriatr Oncol ; 10(1): 31-41, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29706424

RESUMO

OBJECTIVE: The aim of this systematic review was to investigate patient-related factors (e.g. depressive symptoms, cognition, mobility, activities of daily living (ADL)) as well as tumor-related factors (e.g. tumor type, chemotherapy regimen) influencing chemotherapy intolerance in cancer patients aged 65 years or older. METHODS: We included observational studies that reported data on possible predictors of chemotherapy intolerance in older patients with cancer. We studied chemotherapy intolerance using the following outcomes: chemotherapy toxicity grade 3 to 5, unplanned hospitalization, chemotherapy discontinuation, chemotherapy dose reduction, functional decline, and chemotherapy mortality. We searched PubMed, Embase, and PsycInfo for articles between January 1995 and July 2016. The quality of the included studies was assessed using the Quality in Prognosis Studies (QUIPS) tool. RESULTS: The search yielded 1774 articles, and 30 articles from 27 studies were included. The patient-related factors associated with chemotherapy intolerance, in terms of the size of the association and the consistency of the results, were more than one fall in the last six months, mobility problems, poor performance status and the presence of severe comorbid conditions. The tumor-related factors that were associated with chemotherapy intolerance in older patients with cancer were certain regimens of chemotherapy and polychemotherapy, as compared to monochemotherapy. The number of studies on unplanned hospitalization and functional decline was small. CONCLUSION: The included studies were heterogeneous with respect to endpoints and included parameters. Nevertheless, the size of the association and the consistency of results suggest that all these factors are relevant for everyday oncological practice.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias/tratamento farmacológico , Fatores Etários , Idoso , Antineoplásicos/uso terapêutico , Humanos
8.
Front Oncol ; 8: 154, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29868476

RESUMO

Brain metastases (BM) frequently occur in non-small cell lung cancer (NSCLC) patients. Most patients with BM have a limited life expectancy, measured in months. Selected patients may experience a very long progression-free survival, for example, patients with a targetable driver mutation. Traditionally, whole-brain radiotherapy (WBRT) has been the cornerstone of the treatment, but its indication is a matter of debate. A randomized trial has shown that for patients with a poor prognosis, WBRT does not add quality of life (QoL) nor survival over the best supportive care. In recent decades, stereotactic radiosurgery (SRS) has become an attractive non-invasive treatment for patients with BM. Only the BM is irradiated to an ablative dose, sparing healthy brain tissue. Intracranial recurrence rates decrease when WBRT is administered following SRS or resection but does not improve overall survival and comes at the expense of neurocognitive function and QoL. The downside of SRS compared with WBRT is a risk of radionecrosis (RN) and a higher risk of developing new BM during follow-up. Currently, SRS is an established treatment for patients with a maximum of four BM. Several promising strategies are currently being investigated to further improve the indication and outcome of SRS for patients with BM: the effectivity and safety of SRS in patients with more than four BM, combining SRS with systemic therapy such as targeted agents or immunotherapy, shared decision-making with SRS as a treatment option, and individualized isotoxic dose prescription to mitigate the risk of RN and further enhance local control probability of SRS. This review discusses the current indications of SRS and future directions of treatment for patients with BM of NSCLC with focus on the value of SRS.

9.
Clin Transl Radiat Oncol ; 8: 22-26, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29594239

RESUMO

Eekers et al. have recently proposed a neuro-oncology atlas, which was co-authored by most centers associated in the European Proton Therapy Network (EPTN; Figure 1). With the introduction of new treatment techniques, such as integrated magnetic resonance imaging and linear accelerators (MR-linac) or particle therapy, the prediction of clinical efficacy of these more costly treatment modalities becomes more relevant. One of the side-effects of brain irradiation, being cognitive decline, is one of the toxicities most difficult to measure and predict. In order to validly compare different treatment modalities, 1) a uniform nomenclature of the organs at risk (OARs), 2) uniform atlas-based delineation [e.g., Eekers et al.], 3) long-term follow-up data with standardized cognitive tests, 4) a large patient population, and 5) (thus derived) validated normal tissue complication probability (NTCP) models are mandatory. Apart from the Gondi model, in which the role of the dose to 40% of both hippocampi (HC) proves to be significantly related to cognition in 18 patients, no similar models are available. So there is a strong need for more NTCP models, on HC, brain tissue and possible other relevant brain structures. In this review we summarize the available evidence on the role of the posterior cerebellum as a possible new organ at risk for cognition, which is deemed relevant for irradiation of brain and head and neck tumors.

10.
Int J Cancer ; 143(4): 758-766, 2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-29492965

RESUMO

Salivary duct carcinoma (SDC) is a subtype of salivary gland cancer with a dismal prognosis and a need for better prognostication and novel treatments. The aim of this national cohort study was to investigate clinical outcome, prognostic factors, androgen receptor (AR) and human epidermal growth factor receptor 2 (HER2) expression. SDC patients diagnosed between 1990 and 2014 were identified by the Nationwide Network and Registry of Histo- and Cytopathology in the Netherlands (PALGA). Subsequently, medical records were evaluated and pathological diagnoses reviewed. Data were analyzed for overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS) and prognostic factors. AR was evaluated by immunohistochemistry (IHC), HER2 by IHC and fluorescent in-situ hybridization. A total of 177 patients were included. The median age was 65 years, 75% were male. At diagnosis, 68% presented with lymph node metastases and 6% with distant metastases. Median OS, DFS and DMFS were 51, 23 and 26 months, respectively. In patients presenting without distant metastases, the absolute number of positive lymph nodes was associated with poor OS and DMFS in a multivariable analysis. AR and HER2 were positive in 161/168 (96%) and 44/153 (29%) tumors, respectively, and were not prognostic factors. SDC has a dismal prognosis with primary lymph node involvement in the majority of patients. The absolute number of lymph node metastases was found to be the only prognostic factor for DMFS and OS. AR expression and-to a lesser extent-HER2 expression hold promise for systemic treatment in the metastatic and eventually adjuvant setting.


Assuntos
Carcinoma/patologia , Ductos Salivares/patologia , Neoplasias das Glândulas Salivares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/cirurgia , Carcinoma/terapia , Quimiorradioterapia Adjuvante , Intervalo Livre de Doença , Análise Fatorial , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Países Baixos , Cuidados Paliativos , Prognóstico , Receptor ErbB-2/metabolismo , Receptores Androgênicos/metabolismo , Recidiva , Ductos Salivares/cirurgia , Neoplasias das Glândulas Salivares/radioterapia , Neoplasias das Glândulas Salivares/cirurgia , Neoplasias das Glândulas Salivares/terapia , Taxa de Sobrevida
11.
Dis Markers ; 2018: 2908609, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29581794

RESUMO

Glioblastoma is the most aggressive adult primary brain tumor which is incurable despite intensive multimodal treatment. Inter- and intratumoral heterogeneity poses one of the biggest barriers in the diagnosis and treatment of glioblastoma, causing differences in treatment response and outcome. Noninvasive prognostic and predictive tests are highly needed to complement the current armamentarium. Noninvasive testing of glioblastoma uses multiple techniques that can capture the heterogeneity of glioblastoma. This set of diagnostic approaches comprises advanced MRI techniques, nuclear imaging, liquid biopsy, and new integrated approaches including radiogenomics and radiomics. New treatment options such as agents targeted at driver oncogenes and immunotherapy are currently being developed, but benefit for glioblastoma patients still has to be demonstrated. Understanding and unraveling tumor heterogeneity and microenvironment can help to create a treatment regime that is patient-tailored to these specific tumor characteristics. Improved noninvasive tests are crucial to this success. This review discusses multiple diagnostic approaches and their effect on predicting and monitoring treatment response in glioblastoma.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Glioblastoma/diagnóstico por imagem , Terapia de Alvo Molecular/métodos , Imagem Multimodal/métodos , Neuroimagem/métodos , Biópsia/métodos , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Glioblastoma/patologia , Glioblastoma/terapia , Humanos , Imunoterapia/métodos , Imagem por Ressonância Magnética/métodos , Medicina de Precisão , Prognóstico , Resultado do Tratamento
12.
Seizure ; 55: 83-92, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29414140

RESUMO

PURPOSE: Although the majority of adult epilepsy patients respond well to the current antiepileptic drug treatment, 20-40% of them are drug-resistant. In these patients, resective epilepsy surgery is a curative treatment option, for which, however, only a limited number of patients is eligible. The purpose is to summarize the outcome of radiotherapy for drug-resistant non-neoplastic focal epilepsy and to elucidate its efficacy for seizure outcome and long-term toxicity in adults. METHOD: A systematic literature search was performed in Pubmed, Ovid Medline, Cochrane library, Embase and Web of Science. The methodological quality was evaluated using an adapted QUADAS checklist. RESULTS: Sixteen out of 170 initially identified studies were included in this systematic literature study (n = 170 patients). Twelve of the 16 studies described a positive effect of radiotherapy on seizure frequency reduction, with 98 of the patients (on average 58%, range 25%-95%) reporting no or rare seizures (defined as radiotherapy-adapted Engel class [RAEC] I and II. In total, 20% (34 patients) of the patients needed subsequent surgery due to radionecrosis, cysts formation, edema, and intracranial hypertension or remaining seizures. A dose-effect model was fitted to the available response data in an attempt to derive a relationship between prescribed dose and RAEC frequency. CONCLUSIONS: Radiotherapy is a possible non-invasive treatment option for patients with drug-resistant focal non-neoplastic epilepsy. This systematic review showed that there is only level 4 evidence of primary radiotherapy reducing seizure frequency in adult patients. Prospective randomized trials are needed to determine its exact value compared to other treatment approaches.


Assuntos
Epilepsia Resistente a Medicamentos/cirurgia , Epilepsias Parciais/cirurgia , Radiocirurgia , Adulto , Humanos , Resultado do Tratamento
13.
Head Neck ; 40(3): 605-613, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29272069

RESUMO

BACKGROUND: Salivary duct carcinoma, an aggressive subtype of salivary gland cancer, is mostly androgen receptor-positive. Only limited data are available on androgen deprivation therapy (ADT). METHODS: Patients with advanced androgen receptor-positive salivary duct carcinoma treated with first-line ADT were retrospectively evaluated for clinical benefit (ie, partial response [PR] and stable disease, progression-free survival [PFS] and overall survival [OS]). The OS was compared with patients with advanced salivary duct carcinoma who received best supportive care. RESULTS: Thirty-four of 35 patients who were ADT-treated were evaluable: 6 patients had a PR (18%) and 11 had stable disease (32%) leading to a clinical benefit ratio of 50%. The median PFS for the ADT-treated patients was 4 months and the median duration of clinical benefit was 11 months. The median OS was 17 months versus 5 months in 43 patients receiving best supportive care (P = .02). CONCLUSION: We recommend ADT in advanced androgen receptor-positive salivary duct carcinoma given its response and clinical benefit. © 2017 Wiley Periodicals, Inc. Head Neck, 2017.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Ductos Salivares/patologia , Neoplasias das Glândulas Salivares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Países Baixos , Receptores Androgênicos/metabolismo , Sistema de Registros , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/mortalidade , Neoplasias das Glândulas Salivares/patologia , Taxa de Sobrevida , Resultado do Tratamento
14.
Surg Neurol Int ; 8: 223, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28966829

RESUMO

BACKGROUND: In the 2016 update of the World Health Organization Classification of Tumors of the central nervous system, phenotypic and genotypic parameters are integrated in diffuse low-grade glioma (LGG) tumor classification. Implementation of this combined phenotypic-genotypic characterization identifies prognostic relevant subgroups. CASE DESCRIPTION: We report a case of a 67-year-old patient with an LGG that showed molecular characteristics similar to glioblastoma multiforme (GBM). After gross total tumor resection, the patient received combination therapy (radiotherapy and chemotherapy) according to high-grade glioma treatment protocol. CONCLUSION: The introduction of molecular parameters to the classification of LGG will add a level of objectivity, which will yield biological homogeneous subclasses. Consequently, this will influence patient counseling and clinical decision making regarding treatment protocols.

15.
Epigenomics ; 9(9): 1243-1257, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28803494

RESUMO

AIM: Despite numerous published prognostic methylation markers for renal cell carcinoma (RCC), none of these have yet changed patient management. Our aim is to systematically review and evaluate the literature on prognostic DNA methylation markers for RCC. MATERIALS & METHODS: We conducted an exhaustive search of PubMed, EMBASE and MEDLINE up to April 2017 and identified 49 publications. Studies were reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, assessed for their reporting quality using the Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) criteria, and were graded to determine the level of evidence (LOE) for each biomarker. RESULTS: We identified promoter methylation of BNC1, SCUBE3, GATA5, SFRP1, GREM1, RASSF1A, PCDH8, LAD1 and NEFH as promising prognostic markers. Extensive methodological heterogeneity across the included studies was observed, which hampers comparability and reproducibility of results, providing a possible explanation why these biomarkers do not reach the clinic. CONCLUSION: Potential prognostic methylation markers for RCC have been identified, but they require further validation in prospective studies to determine their true clinical value.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Metilação de DNA , Neoplasias Renais/genética , Caderinas/genética , Proteínas de Ligação ao Cálcio/genética , Carcinoma de Células Renais/patologia , Proteínas de Ligação a DNA/genética , Fator de Transcrição GATA5/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Neoplasias Renais/patologia , Proteínas de Membrana/genética , Proteínas de Neurofilamentos/genética , Regiões Promotoras Genéticas , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética
16.
Br J Radiol ; 90(1076): 20170157, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28541096

RESUMO

The advent of immunotherapy is currently revolutionizing the field of oncology, where different drugs are used to stimulate different steps in a failing cancer immune response chain. This review gives a basic overview of the immune response against cancer, as well as the historical and current evidence on the interaction of radiotherapy with the immune system and the different forms of immunotherapy. Furthermore the review elaborates on the many open questions on how to exploit this interaction to the full extent in clinical practice.


Assuntos
Imunoterapia/métodos , Imunoterapia/tendências , Neoplasias/imunologia , Neoplasias/terapia , Terapia Combinada/métodos , Humanos , Neoplasias/radioterapia
17.
Oncologist ; 22(2): 222-235, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28167569

RESUMO

The incidence of brain metastases of solid tumors is increasing. Local treatment of brain metastases is generally straightforward: cranial radiotherapy (e.g., whole-brain radiotherapy or stereotactic radiosurgery) or resection when feasible. However, treatment becomes more complex when brain metastases occur while other metastases, outside of the central nervous system, are being controlled with systemic therapy (chemotherapeutics, molecular targeted agents, or monoclonal antibodies). It is known that some anticancer agents can increase the risk for neurotoxicity when used concurrently with radiotherapy. Increased neurotoxicity decreases quality of life, which is undesirable in this predominantly palliative patient group. Therefore, it is of utmost importance to identify the compounds that should be temporarily discontinued when cranial radiotherapy is needed.This review summarizes the (neuro)toxicity data for combining systemic therapy (chemotherapeutics, molecular targeted agents, or monoclonal antibodies) with concurrent radiotherapy of brain metastases. Because only a limited amount of high-level data has been published, a risk assessment of each agent was done, taking into account the characteristics of each compound (e.g., lipophilicity) and the microenvironment of brain metastasis. The available trials suggest that only gemcitabine, erlotinib, and vemurafenib induce significant neurotoxicity when used concurrently with cranial radiotherapy. We conclude that for most systemic therapies, the currently available literature does not show an increase in neurotoxicity when these therapies are used concurrently with cranial radiotherapy. However, further studies are needed to confirm safety because there is no high-level evidence to permit definitive conclusions. The Oncologist 2017;22:222-235Implications for Practice: The treatment of symptomatic brain metastases diagnosed while patients are receiving systemic therapy continues to pose a dilemma to clinicians. Will concurrent treatment with cranial radiotherapy and systemic therapy (chemotherapeutics, molecular targeted agents, and monoclonal antibodies), used to control intra- and extracranial tumor load, increase the risk for neurotoxicity? This review addresses this clinically relevant question and evaluates the toxicity of combining systemic therapies with cranial radiotherapy, based on currently available literature, in order to determine the need to and interval to interrupt systemic treatment.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/radioterapia , Irradiação Craniana/métodos , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Antineoplásicos/farmacologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/secundário , Feminino , Humanos , Masculino , Metástase Neoplásica , Neoplasias/patologia
18.
Oncotarget ; 8(3): 3870-3880, 2017 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-27965472

RESUMO

Biomarkers predicting treatment response to the monoclonal antibody cetuximab in locally advanced head and neck squamous cell carcinomas (LAHNSCC) are lacking. We hypothesize that tumor accessibility is an important factor in treatment success of the EGFR targeting drug. We quantified uptake of cetuximab labeled with Zirconium-89 (89Zr) using PET/CT imaging.Seventeen patients with stage III-IV LAHNSCC received a loading dose unlabeled cetuximab, followed by 10 mg 54.5±9.6 MBq 89Zr-cetuximab. PET/CT images were acquired either 3 and 6 or 4 and 7 days post-injection. 89Zr-cetuximab uptake was quantified using standardized uptake value (SUV) and tumor-to-background ratio (TBR), and correlated to EGFR immunohistochemistry. TBR was compared between scan days to determine optimal timing.Uptake of 89Zr-cetuximab varied between patients (day 6-7: SUVpeak range 2.5-6.2). TBR increased significantly (49±28%, p < 0.01) between first (1.1±0.3) and second scan (1.7±0.6). Between groups with a low and high EGFR expression a significant difference in SUVmean (2.1 versus 3.0) and SUVpeak (3.2 versus 4.7) was found, however, not in TBR. Data is available at www.cancerdata.org (DOI: 10.17195/candat.2016.11.1).In conclusion, 89Zr-cetuximab PET imaging shows large inter-patient variety in LAHNSCC and provides additional information over FDG-PET and EGFR expression. Validation of the predictive value is recommended with scans acquired 6-7 days post-injection.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Cetuximab/farmacocinética , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Radioisótopos/química , Zircônio/química , Idoso , Antineoplásicos Imunológicos/química , Cetuximab/administração & dosagem , Cetuximab/química , Receptores ErbB/metabolismo , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Molecular , Estadiamento de Neoplasias , Resultado do Tratamento
19.
Head Neck ; 39(1): 140-146, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27507299

RESUMO

BACKGROUND: There is an ongoing debate about the value of (neo-)adjuvant chemotherapy in high- and intermediate-grade osteosarcoma of the head and neck. METHODS: All records of patients older than 16 years diagnosed with osteosarcoma of the head and neck in the Netherlands between 1993 and 2013 were reviewed. RESULTS: We identified a total of 77 patients with an osteosarcoma of the head and neck; the 5-year overall survival (OS) was 55%. In 50 patients with surgically resected high- or intermediate-grade osteosarcoma of the head and neck younger than 75 years, univariate and multivariable analysis, adjusting for age and resection margins, showed that patients who had not received chemotherapy had a significantly higher risk of local recurrence (hazard ratio [HR] = 3.78 and 3.66, respectively). CONCLUSION: In patients younger than 75 years of age with surgically resected high- and intermediate-grade osteosarcoma of the head and neck, treatment with (neo-)adjuvant chemotherapy resulted in a significantly smaller risk of local recurrence. Therefore, we suggest (neo-)adjuvant chemotherapy in patients amenable to chemotherapy. © 2016 The Authors Head & Neck Published by Wiley Periodicals, Inc. Head Neck 39: 140-146, 2017.


Assuntos
Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Osteossarcoma/tratamento farmacológico , Osteossarcoma/cirurgia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Países Baixos , Osteossarcoma/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
20.
Head Neck ; 38(10): 1564-70, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27224655

RESUMO

BACKGROUND: Sinonasal intestinal-type adenocarcinomas (ITACs) are epithelial tumors of the nasal cavity and the paranasal sinuses, often related to professional exposure to organic dust, mainly wood or leather. It is a rare cancer. If resectable, surgery is the treatment of choice. Postoperative radiotherapy is often indicated to increase local control. Systemic treatment (chemotherapy, targeted agents, or immunotherapy) of irresectable ITACs and/or metastasized disease is less standardized. METHODS: Articles on ITAC histopathology, molecular profile, and current treatment options of this specific tumor were identified and reviewed, using the electronic databases Pubmed, Medline, Cochrane, and Web of Science. RESULTS: This article reviews what is currently known on the histopathology, tumorigenesis, molecular characteristics, and standardized treatment options of ITAC. CONCLUSION: More translational research is needed to identify druggable targets that may lead to a personalized treatment plan in order to improve long-term outcome in patients with locally advanced and/or metastasized ITAC. © 2016 Wiley Periodicals, Inc. Head Neck 38: First-1570, 2016.


Assuntos
Adenocarcinoma , Neoplasias dos Seios Paranasais , Adenocarcinoma/etiologia , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Análise Mutacional de DNA , DNA de Neoplasias , Poeira , Regulação Neoplásica da Expressão Gênica , Humanos , Mutação , Neoplasias Nasais/etiologia , Neoplasias Nasais/patologia , Neoplasias Nasais/terapia , Neoplasias dos Seios Paranasais/etiologia , Neoplasias dos Seios Paranasais/patologia , Neoplasias dos Seios Paranasais/terapia , Prognóstico
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