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1.
Radiat Oncol ; 15(1): 30, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32019553

RESUMO

INTRODUCTION: Local ablative treatment strategies are frequently offered to patients diagnosed with oligometastatic disease. Stereotactic body radiotherapy (SBRT), as ablative treatment option, is well established for lung and liver metastases, whereas for isolated adrenal gland metastases the level of evidence is scarce. MATERIAL AND METHODS: This single-institution analysis of oligometastatic or oligoprogressive disease was limited to patients who received SBRT to adrenal metastasis between 2012 and 2019. Patient, tumor, treatment characteristics, and dosimetric parameters were analyzed for evaluation of their effect on survival outcomes. RESULTS: During the period of review 28 patients received ablative SBRT to their adrenal gland metastases. Most common primary tumors were non-small cell lung cancers (46%) with most patients diagnosed with a single adrenal gland metastasis (61%), which occurred after a median time of 14 months. SBRT was delivered to a median biological effective dose at α/ß of 10 (BED10) of 75 Gy (range: 58-151 Gy). Median gross tumor volume (GTV) and median planning target volume (PTV) were 42 and 111 mL, respectively. The homogeneity and conformity indices were 1.17 (range: 1.04-1.64) and 0.5 (range: 0.4.0.99), respectively, with the conformity index being affected by dose restrictions to organs at risk (OARs) in 50% of the patients. Overall response rate based on RECIST criteria was 86% (CR = 29%, PR = 57%) with 2-year local control (LC) of 84.8%, 2-year progression-free survival (PFS) of 26.3%, and 1-and 2-year overall survival (OS) of 46.6 and 32.0%, respectively. During follow up, only two local recurrences occurred. A trend for superior LC was seen if BED10 was ≥75Gy (p = 0.101) or if the PTV was < 100 ml (p = 0.072). SBRT was tolerated well with only mild toxicity. CONCLUSION: SBRT for adrenal metastases resulted in promising LC with low toxicity. Treatment response appeared to be superior, if SBRT was applied with higher BED. As the close proximity of OARs often limits the application of sufficiently high doses, further dose escalations strategies and techniques should be investigated in future.

2.
BMC Cancer ; 19(1): 1074, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703637

RESUMO

BACKGROUND: Hypofractionated palliative radiotherapy for metastatic lung cancer patients is frequently used in order to ease pain, to increase bone stability, to treat local mass effects, or to prolong progression-free survival at critical sites. Recently introduced, immunotherapy for patients with non-squamous non-small cell lung carcinoma (NSCLC) has significantly improved outcome in this cohort. Preclinical and early clinical data suggest that the combination of photon radiation with programmed death-1 (PD-1) targeting immunotherapies may promote a strong and durable immune response against tumor manifestations both within and beyond radiation targets. METHODS/DESIGN: In the present prospective, two-group, non-randomized, open-label phase II trial, 130 patients with stage IV non-squamous NSCLC in 2nd-line or 3rd-line treatment will be included. 65 patients with a clinical indication for palliative radiotherapy to non-cerebral/non-pulmonary metastatic sites will receive 240 mg nivolumab followed by palliative radiotherapy with 5 × 4 Gray (Gy) = 20 Gy photon radiation, which will be initiated within 72 h after first nivolumab administration (Group A). 65 patients without an indication for radiotherapy will only receive nivolumab (Group B). Nivolumab will be further administered every two weeks in both groups and will be continued until progression and loss of clinical benefit or until occurrence of limiting toxicities. The primary endpoint will be the objective response rate (ORR) according to response evaluation criteria in solid tumors (RECIST) 1.1. Secondary endpoints will be progression-free survival (PFS) according to RECIST 1.1, overall survival, descriptive subgroup analyses according to PD-L1 expression, toxicity and quality of life. Since response patterns following immunotherapies differ from those after conventional cytostatic agents, both objective response rate and progression-free survival will additionally be assessed according to immune-related RECIST (irRECIST) criteria. DISCUSSION: The FORCE study will prospectively investigate response rates, progression-free and overall survival (OS), and toxicity of nivolumab with and without hypofractionated palliative radiotherapy in a group of 130 patients with metastatic non-small cell lung cancer (non-squamous histology) in 2nd-line or 3rd-line treatment. This trial will contribute prospective data to the repeatedly published observation that the combination of hypofractionated photon radiotherapy and medical immunotherapy is not only safe but will also promote antitumoral immune responses. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03044626 (Date of initial registration: 05 January 2017). Eudra-CT Number: 2015-005741-31 (Date of initial registration: 18 December 2015).

3.
Trials ; 20(1): 544, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31470902

RESUMO

BACKGROUND: Large field irradiation had been standard for early-stage follicular lymphoma (FL) for a long time. Although involved field radiotherapy (IF-RT) was recently favored because of the toxicity of large field irradiation, smaller irradiation fields have been accompanied with an increased risk of out-of-field recurrence. The MIR (MabThera® and Involved field Radiation) trial has shown that the combination of IF-RT at a dose of 30-40 Gy with the anti-CD20 antibody rituximab has led to similar efficacy compared with large field irradiation but with markedly reduced side effects. Immune modulating radiation therapy alone using low-dose radiotherapy (LDRT) of 2 × 2 Gy has been shown to be effective in FL. The GAZAI (GAZyvaro and response Adapted Involved-site Radiotherapy) trial aims to prove the efficacy of LDRT in combination with a novel anti-CD20 therapy. METHODS/DESIGN: The GAZAI trial is a non-randomized, open, non-controlled, German, multi-center phase II trial that includes patients with early-stage (I and II) nodular FL (grades 1 and 2) confirmed by central histological review. A maximum of 93 patients will be included in the trial. Patients will receive a combined approach of immunotherapy with the fully humanized anti-CD20 antibody obinutuzumab (Gazyvaro®) and involved site radiotherapy (IS-RT) with 2 × 2 Gy. The primary endpoint of the trial is the rate of metabolic complete response (CR), based on fludeoxyglucose positron emission tomography/computed tomography, after obinutuzumab and 2 × 2 Gy IS-RT in week 18. Secondary endpoints are morphologic CR rate in weeks 7 and 18 and month 6, progression-free survival, toxicity, recurrence patterns, overall survival, and quality of life. Additionally, minimal residual disease response is assessed. The risk for a potentially higher recurrence rate after LDRT will be minimized by additional salvage radiation up to the "full dose" of 40 Gy for patients who have less than a metabolic CR and morphologic partial response/CR, which will be evaluated in week 18, offering a response-adapted approach. DISCUSSION: The goal of this trial is a further reduction of the radiation dose in patients with nodal early-stage FL showing a good response to a combination of LDRT and anti-CD20 immunotherapy and a comparison with the currently published MIR trial. TRIAL REGISTRATION: EudraCT number: 2016-002059-89. ClinicalTrials.gov identifier: NCT03341520 .


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/radioterapia , Terapia Combinada , Humanos , Linfoma Folicular/patologia , Estadiamento de Neoplasias , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Projetos de Pesquisa
4.
J Contemp Brachytherapy ; 11(4): 312-319, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31523231

RESUMO

Purpose: The aim of this study is to evaluate the efficacy and toxicity of post-operative partial breast re-irradiation with multi-catheter brachytherapy after second breast conserving therapy (BCT) in patients with small, low-risk ipsilateral breast tumor recurrence (IBTR). Material and methods: Between 2008 and 2018, 19 consecutive patients with low-risk IBTR (max. rpT1 cN0 cM0, Her2 negative, preferably positive hormone receptor status) who refused mastectomy were treated with salvage lumpectomy, followed by post-operative partial breast re-irradiation with multi-catheter brachytherapy. Eight patients were irradiated using PDR brachytherapy (49.8-50.4 Gy in pulses of 0.5-0.7 Gy) and 11 patients using HDR brachytherapy (34.2 Gy in fractions of 3.8 Gy or 32 Gy in fractions of 4 Gy). All patients had undergone prior BCT for their primary tumor, followed by adjuvant whole breast radiotherapy. Local control (LC), locoregional control (LRC), overall survival (OS), disease-free survival (DFS) as well as toxicity were evaluated in the present study. Results: After a median follow-up of 65 months following IBTR (18-120 months), only one second IBTR in 19 patients was diagnosed 77 months after re-irradiation, resulting in a LC rate of 100% at 5 years. DFS and OS rates were both 100% at 5 years following re-irradiation. Except for the above mentioned second IBTR, no regional or distant relapse was recorded. Regarding toxicity, 63% of patients developed adverse events (CTCAE grade ≤ 2), with fibrosis detected in 37% (7/19) of patients, necrosis in 11% (2/19), hyperpigmentation in 47% (9/19), and telangiectasia in 11% (2/19), respectively. No patient showed a high-grade (CTCAE grade ≥ 3) adverse event. Conclusions: In case of small, low-risk IBTR, adjuvant re-irradiation using multi-catheter brachytherapy is a feasible, safe, and effective treatment method after repeated lumpectomy, and an alternative to mastectomy.

5.
Front Oncol ; 9: 384, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31165041

RESUMO

Introduction: Breast conserving surgery (BCS) followed by postoperative whole breast irradiation (WBI) is the current standard of care for early stage breast cancer patients. Boost to the tumor bed is recommended for patients with a higher risk of local recurrence and may be applied with different techniques. Intraoperative electron radiotherapy (IOERT) offers several advantages compared to other techniques, like direct visualization of the tumor bed, better skin sparing, less inter- and intrafractional motion, but also radiobiological effects may be beneficial. Objective of this retrospective analysis of IOERT as boost in breast cancer patients was to assess acute toxicity and early oncological outcomes. Material and Methods: All patients, who have been irradiated between 11/2014 and 01/2018 with IOERT during BCS were analyzed. IOERT was applied using the mobile linear accelerator Mobetron with a total dose of 10 Gy, prescribed to the 90% isodose. After ensured woundhealing, WBI followed with normofractionated or hypofractionated regimens. Patient reports, including diagnostic examinations and toxicity were analyzed after surgery and 6-8 weeks after WBI. Overall survival, distant progression-free survival, in-breast and contralateral breast local progression-free survival were calculated using the Kaplan-Meier method. Furthermore, recurrence patterns were assessed. Results: In total, 157 patients with a median age of 57 years were evaluated. Postoperative adverse events were mild with seroma and hematoma grade 1-2 in 26% and grade 3 in 0.6% of the patients. Wound infections grade 2-3 occurred in 2.2% and wound dehiscence grade 1-2 in 1.9% of the patients. Six to eight weeks after WBI radiotherapy-dependent acute dermatitis grade 1-2 was most common in 90.9% of the patients. Only 4.6% of the patients suffered from dermatitis grade 3. No grade 4 toxicities were documented after surgery or WBI. 2- and 3-year overall survival and distant progression-free survival, were 97.5 and 93.6, and 0.7 and 2.8%, respectively. In-breast recurrence and contralateral breast cancer rates after 3 years were 1.9 and 2.8%, respectively. Conclusion: IOERT boost during BCS is a safe treatment option with low acute toxicity. Short-term recurrence rates are comparable to previously published data and emphasize, that IOERT as boost is an effective treatment.

6.
Strahlenther Onkol ; 195(7): 677-687, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30972453

RESUMO

PURPOSE: Current research approaches in lymphoma focus on reduction of therapy-associated long-term side effects. Especially in mediastinal lymphoma, proton beam radiotherapy (PT) may be a promising approach for reducing the dose to organs at risk (OAR). PATIENTS: In total, 20 patients were irradiated with active scanning PT at Heidelberg Ion Beam Therapy Center (HIT) between September 2014 and February 2017. For comparative analysis, additional photon irradiation plans with helical intensity-modulated radiotherapy (IMRT) were calculated and quantitative and qualitative dose evaluations were made for both treatment modalities. Toxicity and survival outcomes were evaluated. RESULTS: Clinical target volume coverage was comparable in both treatment modalities and did not significantly differ between IMRT and PT. Nevertheless, PT showed superiority regarding the homogeneity index (HIPT = 1.041 vs. HIIMRT = 1.075, p < 0.001). For all OAR, PT showed significantly higher dose reductions compared with IMRT. In particular, the dose to the heart was reduced in PT (absolute dose reduction of Dmean of 3.3 Gy [all patients] and 4.2 Gy [patients with pericardial involvement]). Likewise, the subgroup analysis of female patients, who were expected to receive higher doses to the breast, showed a higher dose reduction in Dmean of 1.2 Gy (right side) and 2.2 Gy (left side). After a median follow-up of 32 months (range 21-48 months), local and distant progression free survival (LPFS and DPFS) were 95.5% and 95.0%, respectively. Radiotherapy was tolerated well with only mild (grade 1-2) radiation-induced acute and chronic side effects. CONCLUSION: A significant reduction in the dose to the surrounding OAR was achieved with PT compared with photon irradiation, without compromising target volume coverage. Dosimetric advantages may have the potential to translate into a reduction of long-term radiation-induced toxicity in young patients with malignant lymphoma of the mediastinum.


Assuntos
Doença de Hodgkin/radioterapia , Linfoma não Hodgkin/radioterapia , Neoplasias do Mediastino/radioterapia , Terapia com Prótons/métodos , Radiometria/métodos , Radioterapia de Intensidade Modulada/métodos , Adolescente , Adulto , Feminino , Seguimentos , Doença de Hodgkin/patologia , Humanos , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Órgãos em Risco/efeitos da radiação , Resultado do Tratamento , Adulto Jovem
7.
Cancer Manag Res ; 10: 6563-6569, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30555261

RESUMO

Background: Systemic inflammation appears to play a role in the progression of numerous solid tumors by promoting tumor proliferation. Our current study aimed to evaluate the role of inflammatory markers in limited disease (LD) small-cell lung cancer (SCLC) patients undergoing thoracic chemoradiotherapy (TCR). Patients and methods: We retrospectively analyzed a total number of 350 SCLC patients diagnosed with LD SCLC who received TCR between 1999 and 2017 and had available blood tests within 2 weeks prior to the start of TCR. Serum C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH), hemoglobin (Hb) levels, and platelet count (Pc) were evaluated as potential inflammatory markers. Kaplan-Meier survival analysis was performed for overall survival (OS). For comparison of survival curves, the log-rank (Mantel-Cox) test was used. Univariate and multivariate Cox proportional HRs were used to assess the influence of cofactors on OS. Results: Univariate analysis for OS revealed a statistically significant effect for LDH >400 U/L (HR 2.05 U/L; 95% CI 1.29-3.26 U/L; P=0.002), prophylactic cranial irradiation (PCI; HR 0.58; 95% CI 0.40-0.85; P=0.005), CRP >50 mg/L (HR 1.49 mg/L; 95% CI 1.05-2.10 mg/L; P=0.026), and Karnofsky performance scale (KPS) <70% (HR 1.35%; 95% CI 1.02-1.80%; P=0.035). NLR, age (>70 years), Hb levels, and Pc did not influence survival. In multivariate analysis, OS was significantly affected by PCI (HR 0.64; 95% CI 0.43-0.94; P=0.026), LDH >400 U/L (HR 1.91 U/L; 95% CI 1.21-3.05 U/L; P=0.006), and CRP >50 mg/L (HR 1.43 mg/L; 95% CI 1.01-2.04 mg/L; P=0.045). KPS (≤70%) did not influence survival in multivariate analysis. Conclusion: Elevated CRP and LDH seem to be the independent prognostic factors for OS in LD SCLC patients undergoing TCR. However, elevated NLR was not found to be an independent prognostic factor for OS if taken prior to TCR. LDH and CRP are easily available blood tests and do not require additional resources for routine use and could be useful for clinical decision making.

8.
Acta Oncol ; 57(12): 1713-1720, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30264630

RESUMO

BACKGROUND: The purpose of this study was to compare dosimetric differences related to target volume and organs-at-risk (OAR) using 3D-conformal radiotherapy (3DCRT), volumetric modulated arc therapy (VMAT), TomoTherapy (Tomo), proton radiotherapy (PRT), and carbon ion radiotherapy (CIRT) as part of postoperative thymoma irradiation. MATERIAL AND METHODS: This single-institutional analysis included 10 consecutive patients treated with adjuvant radiotherapy between December 2013 and September 2016. CT-datasets and respective RT-structures were anonymized and plans for all investigated RT modalities (3DCRT, VMAT, Tomo, PRT, CIRT) were optimized for a total dose of 50 Gy in 25 fractions. Comparisons between target volume and OAR dosimetric parameters were performed using the Wilcoxon rank-sum test. RESULTS: The best target volume coverage (mean PTV V95% for all patients) was observed for Tomo (97.9%), PRT (97.6%), and CIRT (96.6%) followed by VMAT (85.4%) and 3DCRT (74.7%). PRT and CIRT both significantly reduced mean doses to the lungs, breasts, heart, and esophagus, as well as the spinal cord maximum dose compared with photon modalities. Among photon-based techniques, VMAT showed improved OAR sparing over 3DCRT. Tomo was associated with considerable low-dose exposure to the lungs, breasts, and heart. CONCLUSIONS: Particle radiotherapy (PRT, CIRT) showed superior OAR sparing and optimal target volume coverage. The observed dosimetric advantages are expected to reduce toxicity rates. However, their clinical impact must be investigated prospectively.


Assuntos
Tratamentos com Preservação do Órgão/métodos , Órgãos em Risco/efeitos da radiação , Fótons/efeitos adversos , Terapia com Prótons/efeitos adversos , Timoma/terapia , Neoplasias do Timo/terapia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão/efeitos adversos , Fótons/uso terapêutico , Período Pós-Operatório , Terapia com Prótons/métodos , Lesões por Radiação/prevenção & controle , Radiometria , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/métodos , Radioterapia Conformacional/efeitos adversos , Radioterapia Conformacional/métodos , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Timectomia , Timo/patologia , Timo/cirurgia , Neoplasias do Timo/patologia , Adulto Jovem
9.
Trials ; 19(1): 388, 2018 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-30012190

RESUMO

BACKGROUND: Conventional whole brain radiotherapy (WBRT) has been established as the treatment standard in patients with cerebral metastases from small-cell lung cancer (SCLC), however, it has only modest efficacy and limited prospective data is available for WBRT as well as local treatments such as stereotactic radiosurgery (SRS). METHODS/DESIGN: The present single-center prospective randomized study, conducted at Heidelberg University Hospital, compares neurocognitive function, as objectively measured by significant deterioration in Hopkins Verbal Learning Test - Revised total recall at 3 months. Fifty-six patients will be randomized to receive either SRS of all brain metastases (up to ten lesions) or WBRT. Secondary endpoints include intracranial progression (local tumor progression and number of new cerebral metastases), extracranial progression, overall survival, death due to brain metastases, local (neurological) progression-free survival, progression-free survival, changes in other cognitive performance measures, quality of life and toxicity. DISCUSSION: Recent evidence suggests that SRS might be a promising treatment option for SCLC patients with brain metastases. The present trial is the first to prospectively investigate the treatment response, toxicity and neurocognition of WBRT and SRS in SCLC patients. TRIAL REGISTRATION: Clinicaltrials.gov NCT03297788 . Registered September 29, 2017.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Irradiação Craniana , Neoplasias Pulmonares/patologia , Radiocirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Carcinoma de Pequenas Células do Pulmão/patologia , Ensaios Clínicos Fase II como Assunto , Interpretação Estatística de Dados , Humanos , Estudos Prospectivos , Carcinoma de Pequenas Células do Pulmão/secundário
10.
Cancer Manag Res ; 10: 583-588, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29618938

RESUMO

Background: Treatment of patients with pelvic adenoid cystic carcinoma (ACC) remains a challenge owing to the rarity of the disease, the lack of data, and the relative radioresistance of these tumors. Case reports: This case series presents the results of three patients with recurrent or inoperable pelvic ACC treated with intensity-modulated radiotherapy (IMRT) plus carbon ion (C12) boost. Patients received C12 therapy at a dose of 3 Gray equivalents (GyE) (relative biological effectiveness [RBE]) per fraction up to 24 GyE RBE, followed by 50 GyE of photon IMRT in 25 fractions. Conclusion: IMRT plus C12 ion boost as a definitive or adjuvant treatment for pelvic ACCs seems to be a promising therapeutic option. No unexpected toxicity was detected and the observed toxicity remained consistently low. The initial treatment response is promising and similar to that experienced for head and neck ACCs.

11.
Strahlenther Onkol ; 194(5): 454-461, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29450588

RESUMO

PURPOSE: Retrospective study of effectiveness, toxicity, and relapse patterns after low-dose radiotherapy (LDRT) in patients with low-grade lymphomas. METHODS: 47 patients (median age 64 years) with 50 lesions were treated with LDRT (2â€¯× 2 Gy). In 60%, LDRT was the primary and curative treatment, in 40% offered as second-line therapy in recurrent disease. Histology included follicular (57%) and marginal zone lymphomas (43%). Patients were followed-up regularly clinically (skin) and with CT or MRI scans. RESULTS: Median follow-up was 21 months. 84% of the lesions were extranodal disease (32% orbit, 14% salivary glands, 30% skin, and 8% others). Most lesions were ≤5 cm (90%) with a singular affection (74%). 26% of the patients received rituximab simultaneously. Overall response rate (ORR) was 90% (all lesions), 93.3% (primary treatment), and 85% (recurrence treatment); p = 0.341. 2­year Local progression-free survival (LPFS) for all, curative, and palliative patients was 91.1%, 96.7%, and 83.8%, respectively; p = 0.522. Five relapses were detected: three infield only, and were therefore treated with LDRT or subsequent local RT of 30 Gy. Two patients showed an in- and outfield progression and were consequently treated with chemotherapy. Predictive factors for higher LPFS were tumor size ≤5 cm (p = 0.003), ≤2 previous treatments (p = 0.027), no skin involvement (p = 0.05), singular affection (p = 0.075), and simultaneous rituximab application (p = 0.148). LDRT was tolerated well, without detectable acute or long-term side effects. CONCLUSION: Primary LDRT is an effective treatment with high ORR and long-lasting remissions in a subset of patients with low-grade lymphoma, and may therefore be a curative treatment option for patients with low tumor burden. LDRT with the CD20 antibody obinutuzumab will soon be tested in a prospective multicenter trial.


Assuntos
Linfoma de Zona Marginal Tipo Células B/radioterapia , Linfoma Folicular/radioterapia , Recidiva Local de Neoplasia/etiologia , Dosagem Radioterapêutica , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/radioterapia , Radioterapia Adjuvante , Estudos Retrospectivos
12.
Clin Lung Cancer ; 19(4): 340-345, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29373273

RESUMO

INTRODUCTION: Patients with small-cell lung cancer (SCLC) demonstrate an exception in the treatment of brain metastases (BM), because in patients with SCLC whole brain radiotherapy (WBRT) only is the preferred treatment modality. The purpose of this study was to develop a prognostic score for patients with brain metastases from SCLC treated with WBRT. PATIENTS AND METHODS: The present study was conducted utilizing a single-institution, previously described, retrospective database of patients with SCLC who were treated with WBRT (n = 221). Univariate and multivariate analyses were performed to generate the "brain metastases from SCLC score" (BMS score) based on favorable prognostic factors: Karnofsky performance status (KPS > 70), extracerebral disease status (stable disease/controlled), and time of appearance of BM (synchronous). Furthermore, the disease-specific graded prognostic assessment score as well as the recursive partitioning analysis (RPA) were performed and compared with the new BMS score by using the log-rank (Mantel-Cox) test. RESULTS: BMS score and RPA showed the most significant differences between classes (P < .001). BMS score revealed a mean overall survival (OS) of 2.62 months in group I (0-1 points), 6.61 months in group II (2-3 points), and 12.31 months in group III (4 points). The BMS score also identified the group with the shortest survival (2.62 months in group I), and the numbers of patients in each group were most equally distributed with the BMS score. CONCLUSION: The new BMS score was more prognostic than the RPA and disease-specific graded prognostic assessment scores. The BMS score is easy to use and reflects known prognostic factors in contemporary patients with SCLC treated with WBRT. Future studies are necessary to validate these findings.


Assuntos
Neoplasias Encefálicas/secundário , Indicadores Básicos de Saúde , Neoplasias Pulmonares/patologia , Carcinoma de Pequenas Células do Pulmão/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/radioterapia , Irradiação Craniana , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/radioterapia , Resultado do Tratamento
13.
Strahlenther Onkol ; 194(2): 98-106, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29085978

RESUMO

PURPOSE: Whole brain radiation therapy (WBRT) is historically the standard of care for patients with brain metastases (BM) from small-cell lung cancer (SCLC), although locally ablative treatments are the standard of care for patients with 1-4 BM from other solid tumors. The objective of this analysis was to find prognostic factors influencing overall survival (OS) and intracranial progression-free survival (iPFS) in SCLC patients with single BM (SBM) treated with WBRT. METHODS: A total of 52 patients were identified in the authors' cancer center database with histologically confirmed SCLC and contrast-enhanced magnet resonance imaging (MRI) or computed tomography (CT), which confirmed SBM between 2006 and 2015 and were therefore treated with WBRT. A Kaplan-Meier survival analysis was performed for OS analyses. The log-rank (Mantel-Cox) test was used to compare survival curves. Univariate Cox proportional-hazards ratios (HRs) were used to assess the influence of cofactors on OS and iPFS. RESULTS: The median OS after WBRT was 5 months and the median iPFS after WBRT 16 months. Patients that received surgery prior to WBRT had a significantly longer median OS of 19 months compared to 5 months in the group receiving only WBRT (p = 0.03; HR 2.24; 95% confidence interval [CI] 1.06-4.73). Patients with synchronous disease had a significantly longer OS compared to patients with metachronous BM (6 months vs. 3 months, p = 0.005; HR 0.27; 95% CI 0.11-0.68). Univariate analysis for OS revealed a statistically significant effect for metachronous disease (HR 2.25; 95% CI 1.14-4.46; p = 0.019), initial response to first-line chemotherapy (HR 0.58; 95% CI 0.35-0.97; p = 0.04), and surgical resection (HR 0.36; 95% CI 0.15-0.88; p = 0.026). OS was significantly affected by metachronous disease in multivariate analysis (HR 2.20; 95% CI 1.09-4.45; p = 0.028). CONCLUSIONS: Univariate analysis revealed that surgery followed by WBRT can improve OS in patients with SBM in SCLC. Furthermore, synchronous disease and response to initial chemotherapy appeared to be major prognostic factors. Multivariate analysis revealed metachronous disease as a significantly negative prognostic factor on OS. The value of WBRT, stereotactic radiosurgery (SRS), or surgery alone or in combination for patients with a limited number of BM in SCLC should be evaluated in further prospective clinical trials.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Carcinoma de Células Pequenas/radioterapia , Carcinoma de Células Pequenas/secundário , Irradiação Craniana/métodos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Carcinoma de Células Pequenas/mortalidade , Carcinoma de Células Pequenas/patologia , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Tomografia Computadorizada por Raios X , Resultado do Tratamento
14.
Mol Imaging Biol ; 20(4): 641-649, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29270848

RESUMO

PURPOSE: In patients with Hodgkin (HL) and non-Hodgkin lymphoma (NHL), primary staging, as well as intermediate and late response assessment, is often performed by integrated 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/X-ray computed tomography (PET/CT). The purpose of this analysis was to evaluate if findings in patients with histopathologically proven HL or NHL might correlate with semi-automated density measurements of target lesions (TLs) in the CT component of the integrated PET/CT examination. PROCEDURES: After approval by the institutional review board, 176 lymph nodes (LN) in 90 PET/CT examinations of 90 patients were retrospectively analyzed (HL, 108 TLs out of 55 patients; NHL, 68 TLs out of 35 patients). PET/CT was performed for reasons of primary staging, response evaluation as interim PET, or as final examination after therapy, according to the clinical schedule. Analyses of TLs were performed on the basis of tracer uptake (SUV) 60 min after tracer injection and volumetric CT histogram analysis in non-contrast-enhanced CT. RESULTS: All patients were diagnosed with HL or NHL in a pretreatment biopsy. Prior to therapy induction, staging of all patients was performed using contrast-enhanced CT of the neck to the pelvis, or by [18F]FDG PET/CT. Of the 176 TLs, 119 were classified as malignant, and 57 were benign. Malignant TLs had significantly higher CT density values compared to benign (p < 0.01). CONCLUSION: Density measurements of TLs in patients with HL and NHL correlate with the dignity of TLs and might therefore serve as a complementary surrogate parameter for the differentiation between malignant and benign TLs. A possible density threshold in clinical routine might be a 20-Hounsfield units (HU) cutoff value to rule out benignancy in TLs that are above the 20-HU threshold.


Assuntos
Linfoma/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Adulto , Área Sob a Curva , Feminino , Humanos , Masculino , Curva ROC
15.
Clin Lymphoma Myeloma Leuk ; 17(12): e99-e107, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28993162

RESUMO

BACKGROUND: The objective of the present retrospective analysis was the response evaluation regarding bone density and stability of patients with osteolytic spinal bone lesions due to multiple myeloma after palliative radiotherapy (RT). PATIENTS AND METHODS: Patients with multiple myeloma who had undergone spinal RT from March 2003 to May 2016 were analyzed before and 3 and 6 months after RT. Assessment of spinal stability and bone density was performed using the internationally recognized Taneichi scoring system and measurement of bone density using computed tomography imaging-based Hounsfield units. For statistical analysis, we used the Bowker test, McNemar test, and κ statistics to detect possible asymmetries in the distribution of the Taneichi score over time. We used the Student t test for comparison of the density values (Hounsfield units) before and after treatment. Toxicity was evaluated using the Common Terminology Criteria for Adverse Events, version 4.0. Additionally, overall survival was calculated using the Kaplan-Meier method. RESULTS: We evaluated 130 patients (69% male; 31% female) with multiple myeloma and a median age of 58 years. The median follow-up period was 41 months. Before treatment, 51% of the lesions were classified as unstable. At 3 and 6 months after RT, this rate had decreased to 41% (P = .0047) and 24% (P = .2393), respectively. The computed tomography measurements showed a significant increase in bone density at 3 and 6 months after RT. Acute RT-related grade 1 and 2 complications were detected in 34% of patients. Late side effects (grade 1-2) were detected in 23% of the patients. No severe grade 3 or 4 acute or late toxicities were identified. The median overall survival was 19.7 months for all patients and 6.6 months for patients with a Karnofsky performance score of ≤ 70%. CONCLUSION: To the best of our knowledge, ours is the first report to analyze the bone density and stability in patients with multiple myeloma after RT using a validated scoring system and computed tomography imaging. Palliative RT is an effective method resulting in a significant increase in bone density for local response and stability without severe RT-related toxicity. Furthermore, recalcification could already be detected at 3 months after treatment.


Assuntos
Densidade Óssea/efeitos da radiação , Osso e Ossos/efeitos da radiação , Mieloma Múltiplo/radioterapia , Coluna Vertebral/efeitos da radiação , Adulto , Idoso , Idoso de 80 Anos ou mais , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Estudos Retrospectivos , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/patologia , Tomografia Computadorizada por Raios X/métodos
16.
Front Oncol ; 7: 215, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28975083

RESUMO

INTRODUCTION: This study aimed to evaluate parenchymal and functional lung changes following stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) patients and to correlate radiological and functional findings with patient and treatment characteristics as well as survival. MATERIALS AND METHODS: Seventy patients with early-stage NSCLC treated with SBRT from 2004 to 2015 with more than 1 year of CT follow-up scans were analyzed. Incidence, morphology, severity of acute and late lung abnormalities as well as pulmonary function changes were evaluated and correlated with outcome. RESULTS: Median follow-up time was 32.2 months with 2-year overall survival (OS) of 83% and local progression-free survival of 88%, respectively. Regarding parenchymal changes, most patients only developed mild to moderate CT abnormalities. Mean ipsilateral lung dose (MLD) in biological effective dose and planning target volume size were significantly associated with maximum severity score of parenchymal changes (p = 0.014, p < 0.001). Furthermore, both maximum severity score and MLD were significantly connected with OS in univariate analysis (p = 0.043, p = 0.025). For functional lung changes, we detected significantly reduced total lung capacity, forced expiratory volume in 1 s, and forced vital capacity (FVC) parameters after SBRT (p ≤ 0.001). Multivariate analyses revealed SBRT with an MLD ≥ 9.72 Gy and FVC reduction ≥0.54 L as independent prognostic factors for inferior OS (p = 0.029, p = 0.004). CONCLUSION: SBRT was generally tolerated well with only mild toxicity. For evaluating the possible prognostic impact of MLD and FVC reduction on survival detected in this analysis, larger prospective studies are truly needed.

17.
Radiother Oncol ; 125(2): 317-324, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28919006

RESUMO

BACKGROUND AND PURPOSE: To investigate the prognostic impact of different histological subtypes of non-small cell lung cancer (NSCLC) on outcome following stereotactic body radiotherapy (SBRT) for NSCLC patients. MATERIALS AND METHODS: We analyzed 126 consecutive patients with early-stage adenocarcinoma or squamous cell carcinoma treated with SBRT from 2004 to 2016. Adenocarcinoma patients were further sub-classified as high-risk or low-risk tumors. RESULTS: With a median follow-up time of 22months, 2-year overall survival (OS), local (LC), and distant control (DC) were 68%, 90% and 79%, respectively. For LC, histologic subtype was identified as major independent prognostic factor (p=0.033): while LC was 81% for squamous cell carcinoma patients, LC was significantly improved for high-risk and even more non-high-risk adenocarcinoma patients with 96% and 100%, respectively (p=0.026). The negative prognostic impact of the histologic subtype "squamous cell carcinoma" was not evident when patients received SBRT with higher total doses in EQD2 (2Gy equivalent dose): if patients were treated with a total dose in EQD2≥150Gy, no significant difference in LC for histologic subtypes was detected anymore (p=0.355). CONCLUSION: In the current study, histologic subtypes of NSCLC predicted local control probabilities following SBRT. Prospective, multi-center studies are needed to evaluate the prognostic impact of histology and consecutively the need for SBRT dose adaptation.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Radiocirurgia/métodos , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Adenocarcinoma de Pulmão , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Radiocirurgia/efeitos adversos , Estudos Retrospectivos
18.
J Neurooncol ; 134(1): 205-212, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28560661

RESUMO

The purpose of this study was to evaluate prognostic factors associated with overall survival (OS) and neurological progression free survival (nPFS) in small-cell lung cancer (SCLC) patients with brain metastases who received whole-brain radiotherapy (WBRT). From 2003 to 2015, 229 SCLC patients diagnosed with brain metastases who received WBRT were analyzed retrospectively. In this cohort 219 patients (95%) received a total photon dose of 30 Gy in 10 fractions. The prognostic factors evaluated for OS and nPFS were: age, Karnofsky Performance Status (KPS), number of brain metastases, synchronous versus metachronous disease, initial response to chemotherapy, the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class and thoracic radiation. Median OS after WBRT was 6 months and the median nPFS after WBRT was 11 months. Patients with synchronous cerebral metastases had a significantly better median OS with 8 months compared to patients with metachronous metastases with a median survival of 3 months (p < 0.0001; HR 0.46; 95% CI 0.31-0.67). Based on RPA classification median survival after WBRT was 17 months in RPA class I, 7 months in class II and 3 months in class III (p < 0.0001). Karnofsky performance status scale (KPS < 70%) was significantly associated with OS in both univariate (HR 2.84; p < 0.001) and multivariate analyses (HR 2.56; p = 0.011). Further, metachronous brain metastases (HR 1.8; p < 0.001), initial response to first-line chemotherapy (HR 0.51, p < 0.001) and RPA class III (HR 2.74; p < 0.001) were significantly associated with OS in univariate analysis. In multivariate analysis metachronous disease (HR 1.89; p < 0.001) and initial response to chemotherapy (HR 0.61; p < 0.001) were further identified as significant prognostic factors. NPFS was negatively significantly influenced by poor KPS (HR 2.56; p = 0.011), higher number of brain metastases (HR 1.97; p = 0.02), and higher RPA class (HR 2.26; p = 0.03) in univariate analysis. In this series, the main prognostic factors associated with OS were performance status, time of appearance of intracranial disease (synchronous vs. metachronous), initial response to chemotherapy and higher RPA class. NPFS was negatively influenced by poor KPS, multiplicity of brain metastases, and higher RPA class in univariate analysis. For patients with low performance status, metachronous disease or RPA class III, WBRT should be weighed against supportive therapy with steroids alone or palliative chemotherapy.


Assuntos
Neoplasias Encefálicas/radioterapia , Irradiação Craniana/métodos , Resultado do Tratamento , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Feminino , Humanos , Avaliação de Estado de Karnofsky , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Carcinoma de Pequenas Células do Pulmão/patologia , Análise de Sobrevida
19.
Radiol Oncol ; 51(4): 431-437, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29333122

RESUMO

Background: It is hypothesized that metabolism plays a strong role in cancer cell regulation. We have recently demonstrated improved progression-free survival in patients with glioblastoma who received metformin as an antidiabetic substance during chemoradiation. Although metformin is well-established in clinical use the influence of metformin in glioblastoma is far from being understood especially in combination with other treatment modalities such as radiation and temozolomide. Materials and Methods: In this study, we examined the influence of metformin in combinations with radiation and temozolomide on cell survival (clonogenic survival), cell cycle (routine flow cytometric analysis, FACScan), and phosphorylated Adenosine-5'-monophosphate-activated protein kinase (AMPK) (Phopho-AMPKalpha1 - ELISA) levels in glioblastoma cell lines LN18 and LN229. Results: Metformin and temozolomide enhanced the effectiveness of photon irradiation in glioblastoma cells. Cell toxicity was more pronounced in O6-methylguanine DNA methyltransferase (MGMT) promoter non-methylated LN18 cells. Induction of a G2/M phase cell cycle block through metformin and combined treatments was observed up to 72 h. These findings were associated with elevated levels of activated AMPK levels in LN229 cells but not in LN18 cells after irradiation, metformin, and temozolomide treatment. Conclusions: Radiosensitizing effects of metformin on glioblastoma cells treated with irradiation and temozolomide in vitro coincided with G2/M arrest and changes in pAMPK levels.

20.
Clin Transl Radiat Oncol ; 7: 79-82, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29594233

RESUMO

This case report shows the high PSMA-uptake in a patient with an adenoid cystic carcinoma of the maxillary sinus. Due to the intense ligand-uptake additional information for target volume delineation was obtained and the Treatment plan for bimodal radiotherapy with carbon ions was adapted accordingly.

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