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1.
Radiother Oncol ; 146: 16-20, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32086047

RESUMO

PURPOSE: To report the pattern of relapse within the prostate with reference to the initial site of disease in patients treated with single fraction 19-Gy. METHODS AND MATERIALS: Forty-four patients were treated according to a prospective study of single-fraction HDR-brachytherapy. Treatment was delivered using 192Ir to a dose of 19 Gy prescribed to the prostate. Patients who experienced a biochemical failure underwent a re-staging multiparametric MRI (mpMRI) and MRI-TRUS fusion biopsy to rule-out local recurrence. In patients with visible Dominant intraprostatic lesions (DIL) on pretreatment mpMRI, the site of local relapse was compared with the initial site of disease. The dose received by the site of recurrence was investigated. RESULTS: The median follow-up period was 48 months (range 29-63). The PSA nadir was reached at 24 months follow-up, with a median value of 1.07 ng/mL. To date, 14 patients (32%) have experienced biochemical failure (4 patients low-risk and 10 intermediate-risk; p = 0.013). Re-staging mpMRI was performed in 11/14 patients. Eleven patients underwent MRI-TRUS fusion biopsy confirming local relapse in all patients. The analysis of DVH of all 44 patients revealed that patients with biochemical failure had received significantly lower doses in terms of V100, V125 and D90 (p = 0.032, p = 0.018 and p = 0.018 respectively). In patients with DILs on diagnostic mpMRI, the mean D90 and D98 on DIL were lower for patients with biochemical failure. CONCLUSIONS: This dosimetric analysis demonstrates a dose-response relationship in patients treated with single fraction 19 Gy. Patients with intermediate risk disease, with visible DIL on mpMRI and patients treated with cooler implants have higher incidence of biochemical and local failure.

2.
Int J Radiat Oncol Biol Phys ; 106(4): 780-789, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31812719

RESUMO

OBJECTIVE: To investigate precision radiation therapy for metastatic spinal cord compression and compare it to conventional radiation therapy. METHODS AND MATERIALS: In a multicenter phase 2 study, 40 patients received 5 Gy × 5 fractions of precision radiation therapy (38 volume modulated arc therapy, 2 intensity modulated radiation therapy) for metastatic spinal cord compression and were evaluated for local progression-free survival (LPFS), motor function, ambulatory status, sensory function, sphincter dysfunction, pain, distress, overall survival (OS), and toxicity. Maximum spinal cord dose was 101.5% (myelopathy risk, <0.03%) of the prescription dose. Patients were compared with a historical control group conventionally irradiated with 4 Gy × 5 fractions (propensity score analysis). The equivalent dose in 2 Gy-fractions of 5 Gy × 5 fractions is similar to 3 Gy × 10 fractions, which results in better LPFS than 4 Gy × 5 fractions. It was assumed that 5 Gy × 5 fractions is also superior to 4 Gy × 5 fractions for LPFS. (ClinicalTrials.gov-identifier: NCT03070431) RESULTS: Six-month rates of LPFS and OS were 95.0% and 42.6%, respectively. Improvement of motor function occurred in 24 patients (60%). Thirty-three patients (82.5%) were ambulatory after radiation therapy. Eight of 16 patients (50.0%) with sensory deficits improved. Pain and distress relief were reported by 61.9% and 54.2% of patients 1 month after radiation therapy. Grade 3 toxicities occurred in 1 patient and grade 2 toxicities in another 3 patients. Of the control group, 664 patients qualified for the propensity score analysis; 5 Gy × 5 fractions was significantly superior to 4 Gy × 5 fractions with regard to LPFS (P = .026) but not motor function (P = .51) or OS (P = .82). CONCLUSIONS: Precision radiation therapy with 5 Gy × 5 fractions was well tolerated and effective and appeared superior to 4 Gy × 5 fractions in terms of LPFS. The retrospective nature of the historic control group, which might have led to a hidden selection bias, needs to be considered when interpreting the results.

3.
BMC Cancer ; 19(1): 1163, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31783816

RESUMO

BACKGROUND: Patients with metastatic spinal cord compression (MSCC) and favorable survival prognoses can benefit from radiation doses greater than 30Gy in 10 fractions in terms of improved local progression-free survival (LPFS) and overall survival (OS). METHODS/DESIGN: This prospective study mainly investigates LPFS after precision radiotherapy (volumetric modulated arc therapy or stereotactic body radiotherapy) with 18 × 2.33Gy in 3.5 weeks. LPFS is defined as freedom from progression of motor deficits during radiotherapy and an in-field recurrence of MSCC following radiotherapy. The maximum relative dose allowed to the spinal cord is 101.5% of the prescribed dose, resulting in an equivalent dose in 2Gy-fractions (EQD2) for radiation myelopathy is 45.5Gy, which is below the tolerance dose of 50Gy according to the Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC). The EQD2 of this regimen for tumor cell kill is 43.1Gy, which is 33% higher than for 30Gy in 10 fractions (EQD2 = 32.5Gy). Primary endpoint is LPFS at 12 months after radiotherapy. Secondary endpoints include the effect of 18 × 2.33Gy on motor function, ambulatory status, sensory function, sphincter dysfunction, LPFS at other follow-up times, overall survival, pain relief, relief of distress and toxicity. Follow-up visits for all endpoints will be performed directly and at 1, 3, 6, 9 and 12 months after radiotherapy. A total of 65 patients are required for the prospective part of the study. These patients will be compared to a historical control group of at least 235 patients receiving conventional radiotherapy with 10x3Gy in 2 weeks. DISCUSSION: If precision radiotherapy with 18 × 2.33Gy results in significantly better LPFS than 10x3Gy of conventional radiotherapy, this regimen should be strongly considered for patients with MSCC and favorable survival prognoses. TRIAL REGISTRATION: Clinicaltrials.gov NCT04043156. Registered 30-07-2019.

4.
Radiother Oncol ; 144: 86-92, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31786422

RESUMO

BACKGROUND AND PURPOSE: Contouring is a critical step in the radiotherapy process, but there is limited research on how to teach it and no consensus about the best method. We summarize the current evidence regarding improvement of contouring skills. METHODS AND MATERIALS: Comprehensive literature search of the Pubmed-MEDLINE database, EMBASE database and Cochrane Library to identify relevant studies (independently examined by two investigators) that included baseline contouring followed by a re-contouring assessment after an educational intervention. RESULTS: 598 papers were identified. 16 studies met the inclusion criteria representing 370 participants (average number of participants per study of 23; range (4-141). Regarding the teaching methodology, 5/16 used onsite courses, 8/16 online courses, and 2/16 used blended learning. Study quality was heterogenous. There were only 3 randomized studies and only 3 analyzed the dosimetric impact of improving contouring homogeneity. Dice similarity coefficient was the most common evaluation metric (7/16), and in all these studies at least some contours improved significantly post-intervention. The time frame for evaluating the learning effect of the teaching intervention was almost exclusively short-time, with only one study evaluating the long-term utility of the educational program beyond 6 months. CONCLUSION: The literature on educational interventions designed to improve contouring performance is limited and heterogenous. Onsite, online and blended learning courses have all been shown to be helpful, however, sample sizes are small and impact assessment is almost exclusively short-term and typically does not take into account the effect on treatment planning. The most effective teaching methodology/format is unknown and impact on daily clinical practice is uncertain.

5.
Int J Radiat Oncol Biol Phys ; 105(4): 760-764, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31415797

RESUMO

PURPOSE: To compare 4 Gy × 5 (1 week) to 3 Gy × 10 (2 weeks) in relieving pain and distress in patients with metastatic epidural spinal cord compression (MESCC). METHODS AND MATERIALS: The randomized SCORE-2 trial compared 4 Gy × 5 (n = 101) to 3 Gy × 10 (n = 102) for MESCC. In this additional analysis, these regimens were compared for their effect in relieving pain and distress. Distress was evaluated with the distress-thermometer (0 = no distress, 10 = extreme distress) and pain on a linear scale (0 = no pain, 10 = worst pain). Relief of distress was defined as decrease of ≥2 points; complete and partial pain relief were defined as achieving a score of 0 points and a decrease ≥2 points, respectively, without increase of analgesic use. This prospective secondary analysis of the SCORE-2 trial aimed to show that 4 Gy × 5 was not inferior to 3 Gy × 10 regarding distress and pain relief. Analyses were performed using the unconditional test of noninferiority for binomial differences based on restricted maximum likelihood estimates (noninferiority margin: -20%). Evaluations were performed before, directly after, and 1, 3, and 6 months after radiation therapy. (ClinicalTrials.gov: NCT02189473). RESULTS: At baseline, median distress scores were 8 (2-10) points in the 4 Gy × 5 group and 8 (2-10) points in the 3 Gy × 10 group. At 1 month, distress relief rates were 58.1% (43/74) and 62.7% (47/75) (difference: -4.6%; 95% confidence interval, -20.0% to +11.1%; P = .025). At baseline, median pain scores were 7 (2-10) and 7 (2-10) points, respectively. At 1 month, complete pain relief rates were 23.5% (16/68) versus 20.0% (14/70) (difference, +3.5%; 95% confidence interval, -10.4% to +17.5%; P < .001), and overall pain relief rates were 52.9% (36/68) versus 57.1% (40/70) (difference, -4.2%; 95% confidence interval, -20.5% to +12.3%; P = .029). Distress and pain relief rates after 4 Gy × 5 were largely comparable to 3 Gy × 10 at all time points. Associated 95% confidence intervals did not point toward any relevant differences. CONCLUSIONS: In patients with MESCC and poor to intermediate survival prognoses, 4 Gy × 5 appeared noninferior to 3 Gy × 10 regarding pain and distress relief.


Assuntos
Manejo da Dor/métodos , Medidas de Resultados Relatados pelo Paciente , Compressão da Medula Espinal/radioterapia , Neoplasias da Coluna Vertebral/radioterapia , Estresse Psicológico/terapia , Idoso , Feminino , Humanos , Masculino , Medição da Dor/estatística & dados numéricos , Prognóstico , Estudos Prospectivos , Qualidade de Vida , Dosagem Radioterapêutica , Compressão da Medula Espinal/complicações , Neoplasias da Coluna Vertebral/complicações , Fatores de Tempo
6.
Clin Lung Cancer ; 20(4): 322-329, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31155476

RESUMO

PURPOSE: To identify prognostic factors and create a survival score to facilitate individualized care of patients with metastatic spinal cord compression (MSCC) from small-cell lung cancer (SCLC). PATIENTS AND METHODS: Radiation regimen plus 9 factors were retrospectively evaluated in 120 patients irradiated for MSCC from SCLC for overall response, improvement of motor deficits, postradiotherapy ambulatory status, local control of MSCC, and overall survival (OS). Factors included age, interval diagnosis of SCLC to radiotherapy (RT) of MSCC, visceral metastases, further bone metastases, gender, time developing motor deficits, pre-RT ambulatory status, number of affected vertebrae, and Eastern Cooperative Oncology Group performance status (ECOG PS). RESULTS: Improvement of motor deficits showed significant associations with ECOG PS 1-2 (P = .018); time developing motor deficits achieved borderline significance (P = .059). Post-RT ambulatory status was significantly associated with slower development of motor dysfunction (P = .003), ambulatory status (P < .001), and ECOG PS 1-2 (P < .001). No factor was significantly associated with overall response and local control. On multivariate analysis, OS was significantly associated with interval from SCLC diagnosis to RT of MSCC (P = .004), visceral metastases (P < .001), ambulatory status (P = .002), and ECOG PS (P = .002). For the survival score, 6-month OS rates related to each of these factors were divided by 10. Patient scores were obtained by adding these factors' scores. Three groups were defined (5, 7-13, and 15-17 points) with 6-month OS rates of 0, 18%, and 77%, respectively (P < .001). CONCLUSION: Predictors of various outcomes were identified and a survival score was created that can support physicians aiming to create personalized treatments to patients with MSCC from SCLC.

7.
Eur J Cancer Care (Engl) ; 28(5): e13093, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31115124

RESUMO

OBJECTIVE: The primary objective of this study was to assess clinical outcomes in patients with oligometastatic prostate cancer recurrence after single or repeated salvage radiation treatment. METHODS: Forty-nine consecutive prostate cancer patients diagnosed with oligometastatic recurrence on Ch-PET have been prospectively treated. Seven (23%) patients had castrate-resistant disease. Clinical outcomes were assessed using the Kaplan-Meier method. Potential prognostic factors were examined using univariate proportional hazards regression. RESULTS: The treatments administered to the initial oligorecurrence sites were intensity-modulated radiotherapy (IMRT) ± ADT (26 patients; 53%) and stereotactic ablative radiotherapy (SABR) ± ADT (23 patients; 47%). With a median follow-up of 24 months (range 6-39), 24 patients developed a biochemical failure. Twenty out of the 24 relapsed patients underwent a second Ch-PET/CT. Seven patients presented poly-metastatic relapse and 10 oligometastatic diseases. Six of 10 patients with a second oligorecurrence were treated again with SABR. Overall, 102 lesions were treated. Local control was detected in 45 (91.8%) patients. No relevant (grade ≥ 2) toxicity was reported, and there was no grade 3 toxicity. On univariate analysis, none of the variables were significantly predicted for clinical disease-free survival. At last follow-up visit, 24 patients (40%) were free from biochemical failure and 37 (71%) patients were free from clinical disease. The 2-year OS and PCSS were 91.8% and 95.9% respectively. CONCLUSION: Salvage IMRT or SBRT of oligometastatic prostate cancer recurrence is associated with a prolonged cDFS. This may result in a longer time to develop castrate-resistant disease and a longer time without systemic therapies.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias Ósseas/terapia , Carcinoma/terapia , Recidiva Local de Neoplasia/terapia , Neoplasias da Próstata/patologia , Radiocirurgia/métodos , Radioterapia de Intensidade Modulada/métodos , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Carcinoma/diagnóstico por imagem , Carcinoma/secundário , Colina/análogos & derivados , Radioisótopos de Flúor , Humanos , Estimativa de Kaplan-Meier , Linfonodos/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/secundário , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Modelos de Riscos Proporcionais , Neoplasias de Próstata Resistentes à Castração/patologia , Terapia de Salvação
8.
Radiother Oncol ; 136: 29-36, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31015126

RESUMO

BACKGROUND AND PURPOSE: Definitive radiation therapy (RT) with or without chemotherapy has become the standard treatment for non-metastatic unresectable non-small cell lung cancer (NSCLC). However, treatment outcomes can differ substantially and patients' genetic background could play a crucial role. Potential associations between single-nucleotide polymorphisms (SNP) in Heat shock protein beta-1 (HSPB1) and survival have been reported in prior single-institution retrospective reports. MATERIALS AND METHODS: The current assay aims to validate such connection in a prospective multicenter study in a European cohort including 181 NSCLC patients. Median follow-up time for all patients was 13 months (range, 3-57 months). RESULTS: The results obtained show an association between the rs2868371 GG genotype and better overall survival (HR: 0.35; 95%CI: 0.13-0.96; p = 0.042) in multivariate analysis. Two-year overall survival rate was 72% for patients carrying the rs2868371 GG genotype versus 36% for those patients harboring the rs2868371 CC/CG genotypes (p = 0.013). Additionally, the rs2868371 GG genotype was found to be associated with better disease-free survival in the multivariate analysis (HR: 0.36; 95%CI: 0.13-0.99; p = 0.048). In silico analysis of the potential functional SNP suggested significant difference in the affinity of the Glucocorticoid Receptor binding site between alternative allelic variants, confirmed by chromatin immunoprecipitation analysis displaying stronger affinity for the risk allele (C). Furthermore, our findings indicate that the rs2868371 influences (mRNA) HSPB1 expression, offering insight into the regulation of HSPB1 transcription. CONCLUSION: The functional HSPB1 rs2868371 promoter variant may affect lung cancer survival by regulation of HSPB1 expression levels through glucocorticoid receptor interaction.

9.
Radiother Oncol ; 135: 13-18, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31015158

RESUMO

PURPOSE: To describe the genitourinary (GU) and gastrointestinal (GI) late toxicity profile and to analyse the clinical and dosimetry outcomes predictors of the combination of EBRT and high-dose-rate (HDR) prostate brachytherapy (BT) for localized prostate cancer. MATERIALS AND METHODS: Between January 2012 and May 2017, 210 patients were included in a prospective protocol. Treatment consisted in HDR-BT (15 Gy single fraction) plus 3DCRT (37.5 Gy/15 fractions). Univariate and multivariate logistic regressions were used to analyse the impact of variables on late toxicity. RESULTS: Median age was 71 (56-82), 12.4% of patients had low, 44.3% intermediate and 41% high-risk prostate cancer. Median prostate volume was 28.4 cc. Median V100, V150, V200 were 98.2%, 27% and 7.4% respectively. Median urethra Dmax, rectum D1cc and D2cc, were 113.5%, 62.2%% and 54.2% respectively. After a median follow-up of 41 months (5-75) late G2 GU and GI late toxicity was observed in 14.8% and 5.2% of patients respectively. Late G3 GU and GI toxicity occurred in 0% and 1% of patients respectively. There were no outcome correlations with late G ≥ 2 GU toxicity on univariate analysis. Previous cardiovascular comorbidity (p = 0.042), and dose to the rectum D2cc (p = 0.016) and D1cc (p = 0.017) were associated with G ≥ 2 GI toxicity. Multivariate analysis showed that rectum D1cc (HR11.56; 95%CI 1.4-92.1; p = 0.021) and prior history of cardiovascular disease (HR3.6; 95%CI 1-12.9; p = 0.045) remained independent predictors of G ≥ 2 GI toxicity. CONCLUSIONS: There is a low incidence of late GU and GI morbidity using single fraction HDR-BT and hypofractionated EBRT. Previous cardiovascular disease and dose to the rectum were observed to correlate with GI toxicity.

10.
Radiat Oncol ; 13(1): 257, 2018 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-30594231

RESUMO

BACKGROUND: Local progression-free survival (LPFS = stable or improved motor function/resolution of paraplegia during RT without in-field recurrence following RT) is important when treating metastatic spinal cord compression (MSCC). An instrument to estimate LPFS was created to identify patients appropriately treated with short-course RT instead of longer-course RT plus/minus decompressive surgery. METHODS: In 686 patients treated with 20 Gy in 5 fractions alone, ten characteristics were retrospectively analyzed for LPFS including age, interval between tumor diagnosis and RT of MSCC, visceral metastases, other bone metastases, primary tumor type, gender, time developing motor deficits, pre-RT gait function, number of vertebrae affected by MSCC, and performance score. Characteristics significantly (p < 0.05) associated with LPFS on multivariate analyses were incorporated in the scoring system. Six-month LPFS rates for significant characteristics were divided by 10, and corresponding points were added. RESULTS: On multivariate analyses, visceral metastases (p < 0.001), tumor type (p = 0.009), time developing motor deficits (p < 0.001) and performance score (p = 0.009) were associated with LPFS and used for the scoring system. Scores for patients ranged between 24 and 35 points. Three groups were designed: 24-28 (A), 29-31 (B) and 32-35 (C) points. Six-month LPFS rates were 46, 69 and 92%, 12-month LPFS rates 46, 63 and 83%. Median survival times were 2 months (61% died within 2 months), 4 months and ≥ 11 months (median not reached). CONCLUSIONS: Most group A patients appeared sub-optimally treated with 20 Gy in 5 fractions. Patients with survival prognoses ≤2 months may be considered for best supportive care or single-fraction RT, those with prognoses ≥3 months for longer-course RT plus/minus upfront decompressive surgery. Many group B and most group C patients achieved long-time LPFS and appeared sufficiently treated with 20 Gy in 5 fractions. However, based on previous data, long-term survivors may benefit from longer-course RT.


Assuntos
Recidiva Local de Neoplasia/mortalidade , Neoplasias/mortalidade , Compressão da Medula Espinal/mortalidade , Neoplasias da Medula Espinal/mortalidade , Idoso , Feminino , Seguimentos , Raios gama , Humanos , Masculino , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Neoplasias/patologia , Neoplasias/radioterapia , Prognóstico , Dosagem Radioterapêutica , Estudos Retrospectivos , Compressão da Medula Espinal/patologia , Compressão da Medula Espinal/radioterapia , Neoplasias da Medula Espinal/radioterapia , Neoplasias da Medula Espinal/secundário , Taxa de Sobrevida , Sobreviventes
11.
Anticancer Res ; 38(12): 6841-6846, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30504399

RESUMO

BACKGROUND/AIM: Prognoses of patients with metastatic epidural spinal cord compression (MESCC) from urothelial carcinoma of the bladder are generally poor. This study aimed to identify prognostic factors that can facilitate personalized care of these patients. PATIENTS AND METHODS: In 46 patients, 10 factors were evaluated for overall response (OR), post-radiotherapy (RT) ambulatory status, local control of MESCC and overall survival (OS). Independent predictors of OS were incorporated in a scoring system. RESULTS: Being ambulatory post-RT was associated with pre-RT ambulatory status (p<0.001) and better performance score (p<0.001). No factor was significantly associated with OR and local control. On multivariate analyses, lack of visceral metastases (p=0.002), being ambulatory pre-RT (p=0.001) and performance score 1-2 (p=0.004) were associated with improved OS. Based on these factors, there were three distinct prognostic groups with 0, 1-2 and 3 points and median OS times of 2, 4 and 11.5 months, respectively. CONCLUSION: Prognostic factors were identified and a new survival score was created that will help physicians aiming to personalize treatment for patients with MESCC from urothelial carcinoma of the bladder.


Assuntos
Carcinoma de Células de Transição/radioterapia , Neoplasias Epidurais/radioterapia , Compressão da Medula Espinal/radioterapia , Neoplasias da Bexiga Urinária/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Neoplasias Epidurais/complicações , Neoplasias Epidurais/mortalidade , Neoplasias Epidurais/secundário , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Projetos de Pesquisa , Estudos Retrospectivos , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/mortalidade , Compressão da Medula Espinal/patologia , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/mortalidade , Neoplasias da Coluna Vertebral/radioterapia , Neoplasias da Coluna Vertebral/secundário , Análise de Sobrevida , Resultado do Tratamento , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia
12.
Int J Mol Sci ; 19(12)2018 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-30544863

RESUMO

An immunophenotyping analysis was performed in peripheral blood samples from seven patients with lung cancer unfit for surgery treated with stereotactic body radiotherapy (SBRT). The objective was to characterize the effect of SBRT on the host immune system. Four patients received 60 Gy (7.5 Gy × 8) and three 50 Gy (12.5 Gy × 4). Analyses were performed before SBRT, 72 h after SBRT, and at one, three, and six months after the end of SBRT. Of note, there was a specific increase of the immunoactive component of the immune system, with elevation of CD56+highCD16+ natural killer (NK) cells (0.95% at baseline to 1.38% at six months), and a decrease of the immunosuppressive component of the immune system, with decreases of CD4+CD25+Foxp3+CDA5RA- regulatory T cells (4.97% at baseline to 4.46% at six months), granulocytic myeloid-derived suppressor cells (G-MDSCs) (from 66.1% at baseline to 62.6% at six months) and monocytic (Mo-MDSCs) (8.2% at baseline to 6.2% at six months). These changes were already apparent at 72 h and persisted over six months. SBRT showed an effect on systemic immune cell populations, which is a relevant finding for supporting future combinations of SBRT with immunotherapy for treating lung cancer patients.


Assuntos
Sistema Imunitário/patologia , Imunofenotipagem , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/radioterapia , Radiocirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Células Supressoras Mieloides/imunologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Reguladores/imunologia
13.
Crit Rev Oncol Hematol ; 130: 51-59, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30196912

RESUMO

Head Neck Cancer of Unknown Primary (HNCUP) is a rare condition, representing approximately 5-10% of all head neck cancers. Radiotherapy, adjuvant or radical, is usually employed in the treatment of those patients. To date, no specific guidelines for the optimal definition of the target volume to be irradiated have been published. In recent years, there have been advances in the knowledge of the molecular biology of HNCUP, its diagnostic imaging and the implementation of sophisticated radiotherapy techniques with enhanced precision in target localization and treatment delivery. These progresses have provided valuable information about the natural history of HNCUP that will allow for establishment of the best treatment for each patient, including standardized, consistent and reproducible target volumes definitions. Several recommendations regarding how to choose volumes when contouring HNCUP in clinical practice are reported, in order to achieve a high rate of loco-regional control while avoiding unnecessary toxicity.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias Primárias Desconhecidas/radioterapia , Guias de Prática Clínica como Assunto/normas , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Humanos , Dosagem Radioterapêutica
14.
Int J Radiat Oncol Biol Phys ; 101(5): 1172-1178, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29861199

RESUMO

PURPOSE: To prospectively determine whether multiparametric magnetic resonance imaging (mpMRI)-based staging is a more accurate independent predictor of outcome than traditional clinical variables for patients undergoing brachytherapy and external beam radiation therapy. METHODS AND MATERIALS: The primary endpoints were biochemical (nadir plus 2 ng/mL) and metastatic failure. Descriptive, univariate, and multivariate competing risks analyses were performed. The cumulative incidence rates were estimated to describe the cumulative risk of the events of interest. The magnitude of the increased risk was estimated using univariate and multivariate subdistribution hazard ratios. RESULTS: A total of 185 patients had undergone prospective treatment (123 with high risk and 62 with intermediate risk). The median age was 71 years (range 56-82). Of the patients, 20.5% had mpMRI-determined (mrT) stage mrT1-mrT2b, 37.3% had mrT2c, 31% had mrT3a, and 11.2% had mrT3b. The Gleason score was 6 in 22.2%, 7 in 49.5%, and 8 to 10 in 28.2%. The median baseline prostate-specific antigen was 11.7 ng/mL (range 2.9-153). After a median follow-up period of 46 months (range 16-70), 15 patients (8.1%) had developed biochemical failure and 9 (4.9%) had developed distant metastases. None of the traditional clinical variables (prostate-specific antigen, Gleason score, clinical stage) predicted for biochemical or metastatic failure. The multivariate competing risk analysis demonstrated that the 2 independent predictors of biochemical failure were the presence of extraprostatic extension (EPE; mrT3a; hazard ratio [HR] 4.80; P = .035) and presence of seminal vesicle invasion (SVI; mrT3b; HR 10.17; P = .003) on mpMRI. The only independent predictor of metastatic failure was the percentage of positive cores on prostate biopsy (HR 13.95; P = .014). After excluding patients with SVI, the only independent predictor of biochemical failure and metastatic failure was the presence of EPE (stage mrT3a) on mpMRI (HR 4.36; P = .042; and HR 5.76; P = .010, respectively). CONCLUSIONS: The pretreatment mpMRI findings might be more accurate independent predictors of the outcome than traditional clinical variables. In particular, the presence of EPE, SVI and a greater percentage of positive cores on biopsy predicted for a worse prognosis.


Assuntos
Imagem por Ressonância Magnética/métodos , Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Idoso , Idoso de 80 Anos ou mais , Biópsia , Braquiterapia/métodos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Próstata/efeitos da radiação , Neoplasias da Próstata/patologia , Reprodutibilidade dos Testes , Risco , Resultado do Tratamento
15.
Artigo em Inglês | MEDLINE | ID: mdl-29797486

RESUMO

INTRODUCTION: To evaluate whether age is a predictor of pain response after radiotherapy for painful bone metastasis (BM). METHODS: Between June 2010 and June 2014, 204 patients with BM undergoing palliative radiotherapy participated in a multicentre prospective study. Patients completed the Brief Pain Inventory (BPI) to rate the intensity pain (from 0 to 10) at baseline and 4 weeks after radiotherapy. To determine which variables predicted pain response and particularly whether age is a predictor, logistic regression analysis was used. Baseline variables considered were: age (≤65/66-75/>75 years), sex, Eastern Cooperative Oncology Group performance status (0-1/≥2), pretreatment pain score (≤4/5-7/≥8), radiotherapy (single/multiple fraction), primary tumour location, visceral metastases (yes/no), concomitant systemic chemotherapy and bisphosphonate use (yes/no). RESULTS: Pain response was assessed in the 128 patients who completed BPI pretreatment and at 4 weeks after radiotherapy. According to univariate analysis, pain response was better in over 75-year-olds than younger patients: (OR, 3.2; 95% CI, 1.1-9.1; P = 0.031). Response was better in patients receiving multiple fractions rather than a single fraction of 8 Gy (OR, 2.8; 95% CI, 1.2-6.1; P = 0.01), and in patients with a pretreatment pain score ≥8 vs ≤7 (OR, 2.4; 95% CI, 1.1-5.0; P = 0.017). No other variables were significant. Multivariate analysis showed that treatment schedule (OR, 3.4; 95% CI 1.4-7.9; P = 0.004) and pre-radiotherapy pain score (OR, 2.8; 95% CI 1.3-6.3; P = 0.009) were the only independent predictors of pain response. CONCLUSION: All patients with painful bone metastasis should be referred for palliative radiotherapy to relieve the pain regardless of age. Therefore, an older age should not be a reason to withhold palliative radiation treatment.

16.
Radiat Oncol ; 13(1): 21, 2018 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-29422106

RESUMO

BACKGROUND: This study provides separate comparisons of 1 × 8 Gy to 5 × 4 Gy for metastatic epidural spinal cord compression (MESCC) in patients with poor, intermediate and favorable survival prognoses. METHODS: Patients receiving 1 × 8 Gy were matched to patients receiving 5 × 4 Gy for age, gender, performance status, tumor type, involved vertebrae, other bone metastases, visceral metastases, interval between tumor diagnosis and MESCC, ambulatory status and time developing motor deficits. From a study including patients with poor (N = 156) or intermediate (N = 86) survival prognoses, subgroup analyses were performed. Furthermore, 232 new patients with favorable prognoses matched the same way were included. RESULTS: In poor prognoses patients, 6-month survival rates were 10% after 1 × 8 Gy and 6% after 5 × 4 Gy (p = 0.38); in-field reRT rates in few patients alive at 6 months were 15 and 2% (p = 0.16). In intermediate prognoses patients, 6-month survival rates were 49% after 1 × 8 Gy and 58% after 5 × 4 Gy (p = 0.30). ReRT rates at 6 months were 23 and 13% (p = 0.25). In favorable prognoses patients, 6-month survival rates were 89% after 1 × 8 Gy and 91% after 5 × 4 Gy. ReRT rates at 6 months were 14 and 3% (p = 0.007). In no subgroup, RT regimen had a significant impact on motor function. CONCLUSIONS: Since in patients with poor prognoses, outcomes after 1 × 8 Gy and 5 × 4 Gy were not significantly different, 1 × 8 Gy may be an option. In patients with intermediate prognoses, a trend was found in favor of 5 × 4 Gy. In patients with favorable prognoses, need for in-field reRT was greater after 1 × 8 Gy.


Assuntos
Metástase Neoplásica/radioterapia , Compressão da Medula Espinal/radioterapia , Neoplasias da Coluna Vertebral/radioterapia , Neoplasias da Coluna Vertebral/secundário , Adulto , Idoso , Fracionamento da Dose de Radiação , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/patologia , Neoplasias/patologia , Prognóstico , Dosagem Radioterapêutica , Estudos Retrospectivos , Compressão da Medula Espinal/etiologia , Taxa de Sobrevida , Resultado do Tratamento
17.
Anticancer Res ; 38(2): 1009-1015, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29374734

RESUMO

BACKGROUND/AIM: According to our randomized trial, 5×4Gy was comparable to 10×3Gy for metastatic spinal cord compression. Since it remained unclear whether findings applied to poor and intermediate prognoses patients, subgroup analyses were performed. PATIENTS AND METHODS: In patients with poor prognoses, 58 received 5×4Gy, 53 received 10×3Gy. In intermediate-prognoses patients, numbers were 43 and 49. RESULTS: In patients with poor prognoses, 1-month overall response (OR) was 85% after 5×4Gy and 10×3Gy (p=0.99), improvement 38% vs. 42%, ambulatory status 60% vs. 64% (p=0.83), 6-month local progression-free survival (LPFS) 75% vs. 69% (p=0.74) and 6-month overall survival (OS) 26% vs. 19% (p=0.43). In patients with intermediate prognoses, 1-month OR was 89% after 5×4Gy and 93% after 10×3Gy (p=0.85), improvement 39% vs. 45%, ambulatory status 84% vs. 82% (p=0.90), 6-month LPFS 79% vs. 92% (p=0.17) and 6-months OS 65% vs. 58% (p=0.65). CONCLUSION: 5×4Gy was not significantly inferior to 10x3Gy in both subgroups.


Assuntos
Fracionamento da Dose de Radiação , Neoplasias/radioterapia , Compressão da Medula Espinal/radioterapia , Neoplasias da Coluna Vertebral/radioterapia , Idoso , Feminino , Seguimentos , Humanos , Masculino , Neoplasias/complicações , Neoplasias/patologia , Prognóstico , Estudos Retrospectivos , Compressão da Medula Espinal/etiologia , Neoplasias da Coluna Vertebral/secundário , Taxa de Sobrevida
18.
Radiother Oncol ; 126(2): 278-282, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29153462

RESUMO

PURPOSE: To evaluate the safety, tolerance and impact on health-related-quality-of-life (HRQoL) of the high-dose-rate brachytherapy of 19 Gy (BRT-HDR-19 Gy) single fraction in prostate cancer. METHODS: From January 2014 to July 2016, 43 patients with low/intermediate risk were treated with BRT-HDR-19 Gy. The patients were monitored prospectively for toxicity and HRQoL. RESULTS: The median age, initial PSA and the International Prostate Symptom Score (IPSS) were 71 years (55-78), 7.0 ng/mL (4.2-17.8) and 5 (0-14) respectively. 44% were low-risk and 56% intermediate-risk. Median CTV-V100 (where Vn is the fractional volume of the organ that receives n% of the prescribed dose) was 96.5%, Urethral-Dmax 106% and rectum-2 cc (the dose to 2 cc of rectal wall) 53%. After a median follow-up of 20 months (4-26), acute grade-2 genitourinary (GU) toxicity occurred in 4 patients (9%) and none presented acute gastrointestinal (GI) toxicity. Similarly, four patients (9%) presented late GU grade-2 toxicity. No grade-3 toxicity occurred. In terms of HRQoL, there was a statistically significant decline in Expanded Prostate Cancer Index Composite (EPIC) urinary urgency/obstructive domain at month 3 (p = 0.047), and returned to baseline by month 6. Mean EPIC urinary incontinence, bowel, sexual and hormonal domains did not present significant post BRT-HDR-19 Gy changes. Patients rated their satisfaction at 6 months as "very-satisfied" (23%) or "extremely-satisfied" (77%). CONCLUSIONS: BRT-HDR-19 Gy demonstrates excellent results in terms of toxicity, tolerance, safety, patient satisfaction and HRQoL.


Assuntos
Braquiterapia/efeitos adversos , Braquiterapia/métodos , Neoplasias da Próstata/radioterapia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Neoplasias da Próstata/patologia , Qualidade de Vida , Lesões por Radiação/etiologia , Transtornos Urinários/etiologia
19.
BMC Cancer ; 17(1): 818, 2017 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-29202720

RESUMO

BACKGROUND: For metastatic spinal cord compression (MSCC), conventional radiotherapy with 10 × 3 Gy in 2 weeks results in better local progression-free survival (LPFS) than 5 × 4 Gy in 1 week. Since patients with MSCC are often significantly impaired, an overall treatment time of 1 week would be preferable if resulting in similar outcomes as longer programs. This may be achieved with 5 × 5 Gy in 1 week, since the biologically effective dose is similar to 10 × 3 Gy. It can be expected that 5 × 5 Gy (like 10 × 3) Gy results in better LPFS than 5 × 4 Gy in 1 week. METHODS/DESIGN: This phase 2 study investigates LPFS after high-precision RT with 5 × 5 Gy in 1 week. LPFS is defined as freedom from both progression of motor deficits during RT and new or progressive motor deficits dur to an in-field recurrence of MSCC following RT. Considering the tolerance dose of the spinal cord, 5 × 5 Gy can be safely administered with high-precision radiotherapy such as volumetric modulated arc therapy (VMAT) or stereotactic body radiotherapy (SBRT). Maximum dose to the spinal cord should not exceed 101.5% of the prescribed dose to keep the risk of radiation myelopathy below 0.03%. Primary endpoint is LPFS at 6 months following radiotherapy; secondary endpoints include motor function/ability to walk, sensory function, sphincter dysfunction, LPFS directly and 1 and 3 months following radiotherapy, overall survival, pain relief, quality of life and toxicity. Follow-up visits will be performed directly and at 1, 3 and 6 months following radiotherapy. After completion of this phase 2 study, patients will be compared to a historical control group receiving conventional radiotherapy with 5 × 4 Gy in 1 week. Forty-four patients will be included assuming 5 × 5 Gy will provide the same benefit in LPFS when compared to 5 × 4 Gy as reported for 10 × 3 Gy. DISCUSSION: If superiority regarding LPFS is shown for high-precision radiotherapy with 5 × 5 Gy when compared to conventional radiotherapy with 5 × 4 Gy, patients with MSCC would benefit from 5 × 5 Gy, since high LPFS rates could be achieved with 1 week of radiotherapy instead of 2 weeks (10 × 3 Gy). TRIAL REGISTRATION: clinicaltrials.gov NCT03070431 . Registered 27 February 2017.


Assuntos
Transtornos Motores/terapia , Compressão da Medula Espinal/radioterapia , Neoplasias da Coluna Vertebral/radioterapia , Ensaios Clínicos Fase II como Assunto , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Humanos , Transtornos Motores/etiologia , Estudos Multicêntricos como Assunto , Planejamento da Radioterapia Assistida por Computador , Compressão da Medula Espinal/complicações , Neoplasias da Coluna Vertebral/secundário
20.
Pract Radiat Oncol ; 7(2): 137-144, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28274397

RESUMO

PURPOSE/OBJECTIVE: A 5×4 Gy program is commonly used for metastatic epidural spinal cord compression (MESCC). It is unclear whether an overall treatment time (OTT) of 5 days (5 consecutive fractions) results in better outcomes than an OTT of 7 days (ie, no irradiation during the weekend). METHODS AND MATERIALS: A total of 111 patients who received 5×4 Gy over 5 consecutive days were retrospectively compared with 277 patients treated with 5×4 Gy over 7 days (no irradiation during the weekend) for effect on motor function, local control of MESCC, and overall survival (OS). Ten further characteristics were evaluated: age, gender, interval tumor diagnosis to MESCC, visceral metastases, other bone metastases, primary tumor type, time developing motor deficits, walking ability, vertebrae involved, and performance status. RESULTS: On multivariate analysis regarding post-radiation therapy motor function, primary tumor type (P = .011) and time developing motor weakness (P < .001) were significant, whereas the OTT did not even achieve significance on univariate analysis (P = .99). On multivariate analysis of local control, visceral metastases (P = .006) were significant. Again, the OTT was not even significant on univariate analysis (P = .81). On multivariate analysis of OS, interval tumor diagnosis to MESCC (P = .015), visceral metastases (P .001), tumor type (P = .003), walking ability (P < .001), and Eastern Cooperative Oncology Group performance score (P < .001) achieved significance. Even on univariate analysis, OTT did not have an effect on OS (P = .79). CONCLUSIONS: Longer OTT did not impair outcomes of irradiation with 5×4 Gy for MESCC; thus, no compensation (for example an additional radiation fraction) is necessary if the radiation treatment is not continued during the weekend.


Assuntos
Fracionamento da Dose de Radiação , Neoplasias Epidurais/radioterapia , Compressão da Medula Espinal/radioterapia , Idoso , Neoplasias Epidurais/complicações , Neoplasias Epidurais/secundário , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Motores/diagnóstico , Transtornos Motores/etiologia , Análise Multivariada , Prognóstico , Lesões por Radiação/diagnóstico , Lesões por Radiação/etiologia , Estudos Retrospectivos , Compressão da Medula Espinal/etiologia , Fatores de Tempo , Resultado do Tratamento , Caminhada
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