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1.
Croat Med J ; 61(3): 215-222, 2020 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-32643337

RESUMO

AIM: To evaluate the efficacy of radiation therapy in alleviating pain and improving the quality of life (QoL) with validated questionnaires in patients with painful bone metastases (BoM). METHODS: This prospective, observational study recruited 167 patients with painful BoM who were treated with palliative radiotherapy (PRT) from February 2015 to February 2018. After the first clinical assessment, the patients filled out specific questionnaires and underwent a fast radiotherapy treatment within 48 hours. The patients were followed up for eight weeks. RESULTS: The median age was 66.30 years. The most common primary cancer was lung cancer (31.1%). The most often prescribed scheme was 8 Gy in one fraction (70%). The patients experienced significant pain response and improved QoL compared with baseline, especially in the first two weeks after radiation. Overall, reduced pain and drug score were reported at two weeks of PRT in 68 (51.5%) and 37 (28%) of patients, respectively. CONCLUSIONS: PRT is an effective treatment option for patients with painful BoM.


Assuntos
Neoplasias Ósseas/radioterapia , Dor do Câncer/radioterapia , Qualidade de Vida/psicologia , Radioterapia Conformacional , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/psicologia , Neoplasias Ósseas/secundário , Dor do Câncer/psicologia , Fracionamento da Dose de Radiação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Cuidados Paliativos/métodos , Estudos Prospectivos , Dosagem Radioterapêutica , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
2.
Adv Exp Med Biol ; 1257: 45-53, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32483729

RESUMO

Although trace amounts of radioactivity are routinely used to detect osteosarcoma, the use of larger therapeutic amounts of radiation is often an unrecognized opportunity to treat metastatic osteosarcoma. This chapter will review a number of approaches to use ionizing radiation in the form of injectable radiopharmaceuticals. Since bone metastases are a common pattern of metastatic spread of cancer in general, a number of bone-seeking radiopharmaceuticals have been developed and FDA approved for treatment of bone metastases. Although osteosarcoma, a bone-forming cancer, would seem ideally suited to be treated with bone seekers, patterns of relapse involving non-ossifying metastases remain a major problem to be overcome. Thus, this review will not only describe experience using a number of bone-seeking radiopharmaceuticals such as 153-samarium-EDTMP, 153-samarium-DOTMP, and 223-radium against osteosarcoma, but also approaches to identify patients who may benefit as well as some means to the improve overall efficacy including combination therapy with routine agents and using nuclear imaging to develop best strategy for use. These include imaging with not only 99mTc-MDP standard bone scans, but also 99mTc-MDP bone scans with SPECT CT, bone-specific sodium fluoride PET-CT (Na18F), and 18FDG-PET-CT. Accurate knowledge of oligometastatic active disease can facilitate more effective use of combination therapy, including radiosensitizers and local control measures, for example, stereotactic body radiotherapy (SBRT) and/or cryoablation to reduce disease burden as well as manage and prevent micrometastatic disease from growing and metastasizing. Finally, a new tumor-specific radiopharmaceutical, CLR 131, may also provide another radiopharmaceutical to treat both osteoblastic and non-ossifying areas of osteosarcoma.


Assuntos
Antineoplásicos , Neoplasias Ósseas , Osteossarcoma , Compostos Radiofarmacêuticos , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/radioterapia , Humanos , Recidiva Local de Neoplasia , Osteossarcoma/tratamento farmacológico , Osteossarcoma/radioterapia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/uso terapêutico
3.
Adv Exp Med Biol ; 1257: 85-94, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32483733

RESUMO

Osteosarcoma relapses not only herald a very poor prognosis but also opportunities to treat this genetically diverse complex cancer in new ways. This review will attempt to show that the field is a rapidly evolving one in which not only cytotoxic agents but also local control strategies and the immune system can be harnessed to improve the prognosis of relapsed patients. The molecular heterogeneity and the difficulty of effectively treating most common patterns of relapse with surgery and/or radiation (lung and/or bone metastases) have been responsible for a wide variety of approaches to learning whether agents are active against osteosarcoma. This chapter will highlight past, current, and potential future approaches to provide more effective systemic therapy for the problem of recurrent metastases of osteosarcoma. These include single-agent trials with a wide variety of agents, radiopharmaceuticals, and immune therapies. Finally, how such efforts are integrated into more effective local control strategies is also discussed.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/cirurgia , Ensaios Clínicos como Assunto , Humanos , Recidiva Local de Neoplasia , Osteossarcoma/tratamento farmacológico , Osteossarcoma/radioterapia , Osteossarcoma/cirurgia
4.
J Cancer Res Ther ; 16(2): 215-221, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32474504

RESUMO

Objective: Osteosarcoma is a malignant bone tumor and is generally treated with radiotherapy combined with radiosensitizers. The aim of the present study was to investigate the radiosensitization effects of berberine on osteosarcoma cells and the role of Rad51 in radiosensitivity by berberine. Materials and Methods: Cells from the human osteosarcoma cell line MG-63 were exposed to γ-ray irradiation (0, 2, 4, 6, and 8 Gy) and berberine (20 µM). Radiosensitivity was evaluated by determining cell viability using an MTT assay. Flow cytometry was used to determine cell cycle and apoptosis. Real-time PCR and western blot were performed to analyze the mRNA and protein expressions of Rad51. The protein levels of E-cadherin and vimentin were also measured to evaluate the epithelial-mesenchymal transition (EMT) process. Tumor invasion was determined by the Boyden chamber assay. Results: Berberine exacerbated the decline in viability of MG-63 cells exposed to γ-rays irradiation at various concentrations (25, 50, 75, and 100 µmol/L) and induced cell cycle arrest in the G2/M phase as well as apoptosis. The mRNA and protein expressions of Rad51 were significantly decreased by berberine in MG-63 cells. Inhibition of Rad51 by B02 enhanced the radiosensitivity of MG-63 cells. Berberine inhibited their invasive capability as well as increased E-cadherin and decreased vimentin protein levels; this indicated that berberine suppressed the EMT process in MG-63 cells exposed to γ-rays irradiation. Conclusion: Berberine enhances the radiosensitivity of MG-63 osteosarcoma cells. Rad51 is a potential target of berberine in the radiosensitization of osteosarcoma.


Assuntos
Berberina/farmacologia , Pontos de Checagem do Ciclo Celular , Sobrevivência Celular , Transição Epitelial-Mesenquimal , Osteossarcoma/radioterapia , Rad51 Recombinase/antagonistas & inibidores , Radiossensibilizantes/farmacologia , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Neoplasias Ósseas/radioterapia , Linhagem Celular Tumoral , Humanos , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Rad51 Recombinase/metabolismo
5.
J Clin Neurosci ; 76: 219-225, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32265080

RESUMO

Whilst surgical resection is traditionally used for the successful eradication of locally aggressive osseous tumors, it is often hazardous or unachievable, particularly in complex anatomic sites, such as the pelvis and spine. The authors present the use of microwave ablation in combination with Zoledronic acid (ZA) administration, alone and with the use of ZA-loaded polymethyl methacrylate (PMMA) to percutaneously treat unresectable bone tumors in 4 patients with giant cell tumors (GCT), multiple myeloma (MM) and breast cancer metastasis.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/radioterapia , Cementoplastia/métodos , Micro-Ondas/uso terapêutico , Ácido Zoledrônico/uso terapêutico , Adolescente , Adulto , Idoso , Neoplasias Ósseas/secundário , Feminino , Humanos , Masculino , Mieloma Múltiplo , Pelve , Polimetil Metacrilato , Terapia por Radiofrequência , Coluna Vertebral
6.
J Surg Oncol ; 121(8): 1249-1258, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32232871

RESUMO

BACKGROUND AND OBJECTIVES: Radiation improves limb salvage in extremity sarcomas. Timing of radiation therapy remains under investigation. We sought to evaluate the effects of neoadjuvant radiation (NAR) on surgery and survival of patients with extremity sarcomas. MATERIALS AND METHODS: A multi-institutional database was used to identify patients with extremity sarcomas undergoing surgical resection from 2000-2016. Patients were categorized by treatment strategy: surgery alone, adjuvant radiation (AR), or NAR. Survival, recurrence, limb salvage, and surgical margin status was analyzed. RESULTS: A total of 1483 patients were identified. Most patients receiving radiotherapy had high-grade tumors (82% NAR vs 81% AR vs 60% surgery; P < .001). The radiotherapy groups had more limb-sparing operations (98% AR vs 94% NAR vs 87% surgery; P < .001). NAR resulted in negative margin resections (90% NAR vs 79% surgery vs 75% AR; P < .0001). There were fewer local recurrences in the radiation groups (14% NAR vs 17% AR vs 27% surgery; P = .001). There was no difference in overall or recurrence-free survival between the three groups (OS, P = .132; RFS, P = .227). CONCLUSION: In this large study, radiotherapy improved limb salvage rates and decreased local recurrences. Receipt of NAR achieves more margin-negative resections however this did not improve local recurrence or survival rates over.


Assuntos
Extremidades/efeitos da radiação , Extremidades/cirurgia , Sarcoma/radioterapia , Sarcoma/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/cirurgia , Bases de Dados Factuais , Extremidades/patologia , Feminino , Humanos , Salvamento de Membro/métodos , Salvamento de Membro/estatística & dados numéricos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Radioterapia Adjuvante , Estudos Retrospectivos , Sarcoma/mortalidade , Sarcoma/patologia , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/radioterapia , Neoplasias de Tecidos Moles/cirurgia , Taxa de Sobrevida , Estados Unidos/epidemiologia , Adulto Jovem
7.
PLoS One ; 15(2): e0224775, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32084139

RESUMO

We have previously reported radiation-induced sensitization of canine osteosarcoma (OSA) to natural killer (NK) therapy, including results from a first-in-dog clinical trial. Here, we report correlative analyses of blood and tissue specimens for signals of immune activation in trial subjects. Among 10 dogs treated with palliative radiotherapy (RT) and intra-tumoral adoptive NK transfer, we performed ELISA on serum cytokines, flow cytometry for immune phenotype of PBMCs, and PCR on tumor tissue for immune-related gene expression. We then queried The Cancer Genome Atlas (TCGA) to evaluate the association of cytotoxic/immune-related gene expression with human sarcoma survival. Updated survival analysis revealed five 6-month survivors, including one dog who lived 17.9 months. Using feeder line co-culture for NK expansion, we observed maximal activation of dog NK cells on day 17-19 post isolation with near 100% expression of granzyme B and NKp46 and high cytotoxic function in the injected NK product. Among dogs on trial, we observed a trend for higher baseline serum IL-6 to predict worse lung metastasis-free and overall survival (P = 0.08). PCR analysis revealed low absolute gene expression of CD3, CD8, and NKG2D in untreated OSA. Among treated dogs, there was marked heterogeneity in the expression of immune-related genes pre- and post-treatment, but increases in CD3 and CD8 gene expression were higher among dogs that lived > 6 months compared to those who did not. Analysis of the TCGA confirmed significant differences in survival among human sarcoma patients with high and low expression of genes associated with greater immune activation and cytotoxicity (CD3e, CD8a, IFN-γ, perforin, and CD122/IL-2 receptor beta). Updated results from a first-in-dog clinical trial of palliative RT and autologous NK cell immunotherapy for OSA illustrate the translational relevance of companion dogs for novel cancer therapies. Similar to human studies, analyses of immune markers from canine serum, PBMCs, and tumor tissue are feasible and provide insight into potential biomarkers of response and resistance.


Assuntos
Transferência Adotiva/métodos , Neoplasias Ósseas/sangue , Neoplasias Ósseas/veterinária , Doenças do Cão/sangue , Células Matadoras Naturais/imunologia , Osteossarcoma/sangue , Osteossarcoma/veterinária , Cuidados Paliativos/métodos , Animais , Biomarcadores Tumorais/sangue , Neoplasias Ósseas/radioterapia , Citocinas/sangue , Citotoxicidade Imunológica , Doenças do Cão/radioterapia , Cães , Feminino , Seguimentos , Granzimas/metabolismo , Masculino , Receptor 1 Desencadeador da Citotoxicidade Natural/metabolismo , Osteossarcoma/radioterapia , Intervalo Livre de Progressão , Transcriptoma/imunologia
8.
Int J Radiat Oncol Biol Phys ; 107(1): 39-47, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32007565

RESUMO

PURPOSE: Stereotactic body radiation therapy (SBRT) has become a widely adopted treatment for patients with oligometastatic disease, despite limited evidence of superiority. We compared pain response and quality of life (QoL) in patients with oligometastatic disease treated with conventionally fractionated 3-dimensional radiation therapy (3DCRT) or SBRT to bone metastases. METHODS AND MATERIALS: We included patients with oligometastatic disease (≤5 lesions within ≤3 organs) treated within the prospective PRESENT cohort. Main outcomes were pain response, clinical local control, and QoL 2, 4, and 8 weeks and 3, 6, and 12 months after treatment. Pain response was assessed only in patients who reported pain at baseline and was defined according to international consensus criteria. RESULTS: Of 131 patients with oligometastatic disease, 66 patients were treated with 3DCRT and 65 patients with SBRT. A pain response was achieved in 81% (3DCRT) versus 84% (SBRT) with a median duration of 23 weeks (range, 1-58) and 24 weeks (range, 0-50), respectively. Reirradiation was needed in 33% versus 5% of the patients, respectively. None of the QoL subscales were significantly different between both groups. CONCLUSIONS: In patients with oligometastatic disease, SBRT to bone metastases did not improve pain response or QoL compared with 3DCRT. Reirradiation was less often needed in the SBRT group.


Assuntos
Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Medidas de Resultados Relatados pelo Paciente , Radiocirurgia , Idoso , Estudos de Coortes , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica
9.
Medicine (Baltimore) ; 99(2): e18756, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914098

RESUMO

RATIONALE: Liver transplantation (LT) is the preferred surgical option for the treatment of early hepatocellular carcinoma (HCC). In contrast, surgical treatment of progressive HCC metastasized to the spine following LT constitutes a considerable challenge. Here, we report the first case of progressive HCC metastasized to the T12 vertebra after local radiotherapy, treated successfully with en bloc lumpectomy following LT for HCC. PATIENT CONCERNS: A 40-year-old man who had undergone LT for the treatment of HCC 2 months prior presented to our clinic with symptoms of progressive back pain. Magnetic resonance imagining (MRI) and positron emission tomography (PET) examinations showed a solitary metastasis at T12 without recurrence in the liver or metastasis to other organs. DIAGNOSES: The patient was diagnosed with HCC metastasized to the T12 vertebra after liver transplantation. INTERVENTIONS: Local radiation therapy of the T12 vertebra was performed; however, the lesion continued to grow one month after irradiation. Accordingly, the patient was treated with en bloc lumpectomy of the T12 vertebra. After surgery, the patient reported significant pain relief. At 11 months post-surgery, a C4 metastasis with spinal cord compression was revealed by MRI. Multiple grafted liver metastases were also detected by ultrasound along with several lung metastases, which were discovered by X-ray. The patient was treated with a pedicle screw system and a mesh cage filled with frozen autografts for C4 metastasis. OUTCOMES: The patient died 15 months after liver transplantation due to recurrence in the liver and metastasis to the lung. LESSONS: En bloc lumpectomy may be a viable therapeutic option for patients with progressive solitary spinal metastases after LT refractory to radiotherapy. Use of immunosuppressive therapy after LT may significantly inhibit immune function, making patients more susceptible to HCC recurrence and bone metastasis.


Assuntos
Neoplasias Ósseas/secundário , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Adulto , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/cirurgia , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/métodos , Masculino , Coluna Vertebral/patologia , Coluna Vertebral/cirurgia
10.
Anticancer Res ; 40(1): 367-371, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892588

RESUMO

BACKGROUND/AIM: Individualization of treatment may improve the outcome of patients with bone metastases from breast cancer. To support physicians when selecting individualized programs for these patients, a simple instrument for predicting survival was created. PATIENTS AND METHODS: In 126 female patients with breast cancer irradiated for bone metastases, 11 characteristics were evaluated with respect to survival. RESULTS: On Cox regression analysis, Eastern Cooperative Oncology Group performance score (0-1 vs. ≥2; p=0.032) and visceral metastases (absence vs. presence; p=0.017) were independently associated with survival and incorporated into the scoring instrument. Three prognostic groups (0, 1 or 2 points) were designated with 12-month survival rates of 38%, 57% and 91%, and 24-month survival rates of 32%, 36% and 80%, respectively (p<0.001). CONCLUSION: This easy-to-use scoring instrument allows physicians to estimate the lifespan of patients irradiated for bone metastases from breast cancer and can facilitate individualization of their treatment.


Assuntos
Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Estimativa de Kaplan-Meier , Probabilidade , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico
11.
PLoS One ; 15(1): e0228360, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31999771

RESUMO

BACKGROUND: Growing evidence indicates that measures of body composition may be related to clinical outcomes in patients with malignancies. The aim of this study was to investigate whether measures of regional adiposity-including subcutaneous adipose tissue index (SATI) and visceral adipose tissue index (VATI)-can be associated with overall survival (OS) in Taiwanese patients with bone metastases. METHODS: This is a retrospective analysis of prospectively collected data. We examined 1280 patients with bone metastases who had undergone radiotherapy (RT) between March 2005 and August 2013. Body composition (SATI, VATI, and muscle index) was assessed by computed tomography at the third lumbar vertebra and normalized for patient height. Patients were divided into low- and high-adiposity groups (for both SATI and VATI) according to sex-specific median values. RESULTS: Both SATI (hazard ratio [HR]: 0.696; P<0.001) and VATI (HR: 0.87; P = 0.037)-but not muscle index-were independently associated with a more favorable OS, with the former showing a stronger relationship. The most favorable OS was observed in women with high SATI (11.21 months; 95% confidence interval: 9.434-12.988; P<0.001). CONCLUSIONS: High SATI and VATI are associated with a more favorable OS in Taiwanese patients with bone metastases referred for RT. The question as to whether clinical measures aimed at improving adiposity may improve OS in this clinical population deserves further scrutiny.


Assuntos
Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Gordura Intra-Abdominal/diagnóstico por imagem , Gordura Subcutânea/diagnóstico por imagem , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/mortalidade , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Taiwan , Tomografia Computadorizada por Raios X , Resultado do Tratamento
12.
Br J Radiol ; 93(1108): 20190353, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31971828

RESUMO

OBJECTIVE: To evaluate toxicity and clinical outcome in synchronous bone only oligometastatic (≤2 lesions) prostate cancer patients, simultaneously irradiated to prostate/prostatic bed, lymph nodes and bone metastases. METHODS: From 2/2009 to 6/2015, 39 bone only prostate cancer patients underwent radiotherapy (RT) at "radical" doses to bone metastases (median 2 Gy equivalent dose, EQD2>40Gy, α/ß = 1,5), nodes, and prostate/prostatic bed, within the same RT course, in association with androgen deprivation therapy (ADT).Biochemical relapse-free survival, clinical relapse-free survival, freedom from distant metastases and overall survival were evaluated. RESULTS: After a median follow-up of 46.5 (1.2-103.6) months, 5 patients died from disease progression, 10 experienced biochemical relapse, 19, still in ADT, presented undetectable prostate-specific antigen (PSA) at the last follow-up. Five patients who discontinued ADT after a median of 34 months (5.8-41) are free from biochemical relapse.The 4 year Kaplan-Meier estimates of biochemical relapse-free survival, clinical relapse-free survival, freedom from distant metastases and overall survival were 53.3%, 65.7%, 73.4% and 82.4% respectively.No Grade > 2 acute events and only two severe late urinary events were recorded, not due to the concomitant treatment of primary and metastatic disease. CONCLUSION: Our results suggest that "radical" and synchronous irradiation of primitive tumor and metastatic disease may be a valid approach in synchronous bone only prostate cancer patients, showing mild toxicity profile and promising survival results. ADVANCES IN KNOWLEDGE: To the best of our knowledge, this is the first analysis of clinical outcome in synchronous bone-only metastasis (neither nodal nor visceral) patients at diagnosis, treated with radical RT to all disease, associated to ADT.


Assuntos
Neoplasias Ósseas/radioterapia , Irradiação Linfática , Neoplasias da Próstata/radioterapia , Idoso , Antagonistas de Androgênios/uso terapêutico , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Quimioterapia Adjuvante , Progressão da Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Estudos Retrospectivos
13.
Support Care Cancer ; 28(9): 4487-4492, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31933067

RESUMO

PURPOSE: International guidelines are available to guide prescription of antiemetic and pain flare medications in patients receiving palliative radiotherapy for bone metastases, but prescription rates are quite variable. We hypothesized that a simple electronic quality checklist could increase the evidence-based use of these medications. MATERIALS AND METHODS: We implemented an electronic quality checklist item in our center for all patients treated with palliative radiotherapy for lumbar spine bone metastases. We retrospectively reviewed patients in the 6-month pre- and post-intervention. Patients were stratified according to if they were treated within a dedicated rapid palliative (RPAL) radiotherapy program or not. Chi-square tests were used to compare rates of antiemetic and pain flare medications pre- and post-intervention and RPAL vs not. RESULTS: A total of 375 patients were identified with 42 (11.2%) treated in dedicated RPAL program. The proportion of patients treated with prophylactic antiemetic and pain flare medications pre-intervention (n = 226) and post-intervention (n = 149) was respectively 34.1% vs 59.1% (p < 0.001) and 26.1% vs 43.0% (p = 0.01). Observed differences for antiemetic prescription rates were greater for patients who were not treated within a dedicated palliative radiotherapy program, but this was not the case for pain flare medications. CONCLUSIONS: Our data shows that a simple quality checklist item can have a significant effect on the evidence-based use of prophylactic antiemetic and pain flare medications in patients treated with palliative radiotherapy for bone metastases. We believe such strategies should be routinely included in other clinical pathways to improve the use of symptom control medications.


Assuntos
Antieméticos/uso terapêutico , Neoplasias Ósseas/radioterapia , Dor/tratamento farmacológico , Cuidados Paliativos/métodos , Radioterapia/métodos , Idoso , Antieméticos/farmacologia , Neoplasias Ósseas/secundário , Lista de Checagem , Feminino , Humanos , Masculino , Metástase Neoplásica , Estudos Retrospectivos
14.
Int J Radiat Oncol Biol Phys ; 106(4): 800-810, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31805367

RESUMO

PURPOSE: Numerous randomized trials have demonstrated noninferiority of single- versus multiple-fraction palliative radiation therapy (RT) in the management of uncomplicated bone metastases; yet there is neither a clear definition of what constitutes a complicated lesion, nor substantial data regarding the prevalence of such complicating features in clinical practice. Thus, we identify a range of evidence-based operational definitions of complicated symptomatic bone metastases and characterize the frequency of such complicating features at a high-volume, tertiary care center. METHODS AND MATERIALS: A retrospective review of patients seen in consultation for symptomatic bone metastases between March 1, 2007, and July 31, 2013, at Johns Hopkins Hospital identified patient and disease characteristics. Descriptive statistics characterized the frequency of the following complicating features: prior RT, prior surgery, neuraxis compromise, pathologic fracture, and soft tissue component at the symptomatic site. A range of definitions for complicated bone metastases was evaluated based on combinations of these features. Uni- and multivariable logistic regressions evaluated the odds of complicated bone metastases as a function of site of primary cancer and of the symptomatic target lesion. RESULTS: A total of 686 symptomatic bone metastases in 401 patients were evaluated. Percent of target sites complicated by prior RT was 4.4%, prior surgery was 8.9%, pathologic fracture was 20.6%, neuraxis compromise was 52.0% among spine and medial pelvis sites, and soft tissue component was 38.6%. More than 96 possible definitions of complicated bone metastases were identified. The presence of such complicated lesions ranged from 2.3% to 67.3%, depending on the operational definition used. Odds of a complicated lesion were significantly higher for spine sites and select nonbreast histologies. CONCLUSIONS: In this retrospective study, we found complicated symptomatic bone metastases may be present in up to two-thirds of patients. Literature review also demonstrates no clear standard definition of complicated bone metastases, potentially explaining underutilization of single-fraction palliative RT in this setting.


Assuntos
Neoplasias Ósseas/secundário , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/radioterapia , Feminino , Humanos , Masculino , Análise Multivariada , Cuidados Paliativos , Análise de Regressão , Estudos Retrospectivos , Resultado do Tratamento
15.
Pediatr Blood Cancer ; 67(2): e28018, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31710168

RESUMO

BACKGROUND: Extraskeletal osteosarcoma is an extremely rare disease, comprising less than 0.1% of all cancers diagnosed in the United States, of which less than 5% occur in the upper extremities. The management of two cases of pediatric upper extremity extraskeletal osteosarcoma is discussed. CASE DESCRIPTION: Two children initially noticed painless left upper extremity masses at the ages of 16 and 13, respectively. Following a period of several months, both lesions became symptomatic, necessitating operative intervention, which revealed giant cell-rich extraskeletal osteosarcoma; PET staging following gross total resection revealed no residual or metastatic disease in either patient. After extensive discussion with the patients and family, adjuvant chemotherapy was initiated for one patient, and adjuvant radiation therapy was initiated in both patients. CONCLUSIONS: Despite the rarity of these tumors, the importance of radiation therapy has been established by current and ongoing studies such as the Children's Oncology Group study ARST0332. Radiation therapy remains an important component of the multimodality therapy comprising optimal treatment of this disease, despite the relative paucity of long-term outcome data derived from level I evidence.


Assuntos
Neoplasias Ósseas/radioterapia , Osteossarcoma/radioterapia , Radioterapia de Alta Energia/métodos , Neoplasias de Tecidos Moles/radioterapia , Extremidade Superior/efeitos da radiação , Adolescente , Neoplasias Ósseas/patologia , Humanos , Masculino , Osteossarcoma/patologia , Fótons , Prognóstico , Neoplasias de Tecidos Moles/patologia
16.
Pediatr Blood Cancer ; 67(2): e28080, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31736243

RESUMO

PURPOSE: Despite the dosimetric advantages of proton therapy, little data exist on patients who receive proton therapy for Ewing sarcoma of the cranium and skull base. This study reports local disease control and toxicity in such patients. MATERIALS/METHODS: We reviewed 25 patients (≤21 years old) with nonmetastatic Ewing sarcoma of the cranium and skull base treated between 2008 and 2018. Treatment toxicity was graded per the Common Terminology Criteria for Adverse Events v4.0. The Kaplan-Meier product limit method provided estimates of disease control and survival. RESULTS: Median patient age was 5.9 years (range, 1-21.7). Tumor subsites included the skull base (48%), non-skull-base calvarial bones (28%), paranasal sinuses (20%), and nasal cavity (4%). All patients underwent multiagent alkylator- and anthracycline-based chemotherapy; 16% underwent gross total resection (GTR) before radiation. Clinical target volume (CTV) 1 received 45 GyRBE and CTV2 received 50.4 GyRBE following GTR or 54-55.8 GyRBE following biopsy or subtotal resection. Median follow-up was 3.7 years (range, 0.26-8.3); no patients were lost. The 4-year local control, disease-free survival, and overall survival rates were 96%, 86%, and 92%, respectively. Two patients experienced in-field recurrences. One patient experienced bilateral conductive hearing loss requiring aids, two patients developed intracranial vasculopathy, and 6 patients required hormone replacement therapy for neuroendocrine deficits. None developed a secondary malignancy. CONCLUSION: Proton therapy is associated with a favorable therapeutic ratio in children with large Ewing tumors of the cranium and skull base. Despite its high conformality, we observed excellent local control and no marginal recurrences. Treatment dosimetry predicts limited long-term neurocognitive and neuroendocrine side effects.


Assuntos
Neoplasias Ósseas/mortalidade , Neoplasias dos Nervos Cranianos/mortalidade , Recidiva Local de Neoplasia/mortalidade , Terapia com Prótons/mortalidade , Sarcoma de Ewing/mortalidade , Neoplasias da Base do Crânio/mortalidade , Adolescente , Adulto , Neoplasias Ósseas/patologia , Neoplasias Ósseas/radioterapia , Criança , Pré-Escolar , Neoplasias dos Nervos Cranianos/patologia , Neoplasias dos Nervos Cranianos/radioterapia , Feminino , Seguimentos , Humanos , Lactente , Masculino , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Prognóstico , Estudos Prospectivos , Dosagem Radioterapêutica , Sarcoma de Ewing/patologia , Sarcoma de Ewing/radioterapia , Neoplasias da Base do Crânio/patologia , Neoplasias da Base do Crânio/radioterapia , Taxa de Sobrevida , Adulto Jovem
17.
J Cancer Res Clin Oncol ; 146(2): 429-439, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31677113

RESUMO

PURPOSE: To compare the clinical results and functional outcomes between two-dimensional conventional radiation therapy (2DRT) and intensity-modulated radiation therapy (IMRT) in nasopharyngeal carcinoma (NPC) with skull-base invasion. METHODS: A total of 1258 patients were subclassified into two groups: mild skull-base invasion group (792; 63%) and severe skull-base invasion group (466; 37%). Patients were pair matched (1:1 ratio) using six clinical factors into 2DRT or IMRT groups. The Kaplan-Meier method and Cox regression model were performed to assess overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS). Toxicities were evaluated. RESULTS: IMRT significantly improved four-year OS compared with 2DRT (65.6% vs. 81.8%, P = 0.000), DFS (57.3% vs. 73.3%, P = 0.000) and LRRFS (76.5% vs. 87.5%, P = 0.003) in NPC with severe skull-base invasion, but similar results were observed in patients with mild skull-base invasion (P > 0.05). In patients with severe invasion, radiation therapy techniques were found to be an independent prognostic factor for OS (HR = 0.457, P = 0.000), DFS (HR = 0.547, P = 0.000) and LRRFS (HR = 0.503, P = 0.004). IMRT was associated with better OS. In subgroups analysis, IMRT group also had a better survival in OS, DFS (P < 0.05 for all rates) for patients received concurrent chemotherapy and sequential chemotherapy compared to 2DRT in the severe invasion group. The IMRT group displayed lower incidence of mucositis, xerostomia, trismus (< 1 cm) and temporal lobe necrosis than the 2DRT group. CONCLUSIONS: IMRT significantly improved patient survival compared with 2DRT in NPC patients with severe skull-base invasion, but a similar survival rate was noted in mild invasion patients. Chemotherapy can improve survival in NPC patients with severe invasion. Among the two therapies, IMRT significantly decreased therapy-related toxicity.


Assuntos
Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Quimiorradioterapia , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Radioterapia de Intensidade Modulada , Estudos Retrospectivos , Base do Crânio/patologia , Adulto Jovem
18.
Br J Radiol ; 93(1107): 20190601, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31529979

RESUMO

Proton beam therapy is a highly conformal form of radiation therapy, which currently represents an important therapeutic component in multidisciplinary management in paediatric oncology. The precise adjustability of protons results in a reduction of radiation-related long-term side-effects and secondary malignancy induction, which is of particular importance for the quality of life. Proton irradiation has been shown to offer significant advantages over conventional photon-based radiotherapy, although the biological effectiveness of both irradiation modalities is comparable. This review evaluates current data from clinical and dosimetric studies on the treatment of tumours of the central nervous system, soft tissue and bone sarcomas of the head and neck region, paraspinal or pelvic region, and retinoblastoma. To date, the clinical results of irradiating childhood tumours with high-precision proton therapy are promising both with regard to tumour cure and the reduction of adverse events. Modern proton therapy techniques such as pencil beam scanning and intensity modulation are increasingly established modern facilities. However, further investigations with larger patient cohorts and longer follow-up periods are required, in order to be able to have clear evidence on clinical benefits.


Assuntos
Neoplasias/radioterapia , Terapia com Prótons/métodos , Neoplasias Ósseas/radioterapia , Neoplasias do Sistema Nervoso Central/radioterapia , Criança , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Neoplasias da Retina/radioterapia , Retinoblastoma/radioterapia , Sarcoma/radioterapia , Neoplasias de Tecidos Moles/radioterapia , Neoplasias da Coluna Vertebral/radioterapia
19.
Urologe A ; 59(1): 53-64, 2020 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-31598745

RESUMO

BACKGROUND: Radium-223 improves overall survival and preserves quality of life in patients with metastatic castration-resistant prostate cancer (mCRPC) and symptomatic bone metastases and no known visceral metastases. Radium-223 can be used in combination with a luteinizing hormone releasing hormone (LHRH) analogue and as part of a sequential treatment scheme if disease progresses after at least two prior lines of systemic mCRPC therapies or if no other available systemic treatment is eligible. OBJECTIVES: Today physicians are faced with a previously unknown multitude and complexity of options for the treatment of mCRPC. An increasing number of clinical trials contribute to the dynamics of the therapeutic landscape. Radium-223 was approved for mCRPC treatment in 2013. Up to now the recommendations of use have been adjusted several times. Highlighting recent clinical trials and practice, this paper explores the position of radium-223 within the therapeutic sequence and outlines key elements for the interdisciplinary cooperation between uro-oncologists and nuclear medicine specialists. RESULTS: The mode of action of radium-223 does not depend on the androgen receptor (AR) pathway. Thus, it is an option in the therapeutic sequence when the efficacy of other agents is reduced by resistance. Furthermore, the efficacy of prior or subsequent medications are neither reduced nor enhanced by radium-223. The opportunity of an AR-independent and survival-prolonging medication should be taken as soon as the indication criteria are met because the incidence of visceral metastases increases during disease progression. According to current mCRPC guidelines, the osteoprotective use of bisphosphonates or denosumab is recommended, before treatment with radium-223 is started or resumed.


Assuntos
Neoplasias Ósseas/radioterapia , Neoplasias de Próstata Resistentes à Castração/radioterapia , Compostos Radiofarmacêuticos/uso terapêutico , Rádio (Elemento)/uso terapêutico , Neoplasias Ósseas/secundário , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , Qualidade de Vida , Receptores Androgênicos/metabolismo
20.
Int J Radiat Oncol Biol Phys ; 106(1): 61-66, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31505246

RESUMO

PURPOSE: To evaluate the use of single-fraction palliative radiation therapy (SFRT) for the management of bone metastases (BM) in Victoria, Australia. METHODS AND MATERIALS: This is a population-based cohort of patients with cancer who received radiation therapy for BM between 2012 and 2017 as captured in the Victorian Radiotherapy Minimum Data Set. The primary outcome was proportion of SFRT use. The Cochrane-Armitage test for trend was used to evaluate changes in practice over time. Multivariable logistic regression was used to assess factors associated with SFRT use. RESULTS: Of the 18,158 courses of radiation therapy for BM delivered to a total of 10,956 patients, 17% were SFRT. There was no significant change in SFRT use over time, from 18% in 2012 to 19% in 2017 (P = .07). SFRT was less commonly given to the skull (4%) and spine (14%), compared with the shoulder (37%) and ribs (53%). Patients with lung cancer (21%) were most likely to receive SFRT, followed by those with prostate cancers (18%) and gastrointestinal cancers (16%). Patients from regional/remote areas were more likely to have SFRT compared with those in major cities (22% vs 16%, P < .001). Patients treated in public institutions were more likely to have SFRT compared with those treated in private institutions (22% vs 10%, P < .001). In multivariable analyses, increasing age, lung cancer, higher socioeconomic status, residence in regional/ remote areas, and being treated in public institutions were factors independently associated with increased likelihood of receiving SFRT. CONCLUSIONS: SFRT appears underused for BM in Australia over time, with variation in practice by patient, tumor, sociodemographic, geographical, and institutional provider factors.


Assuntos
Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Cuidados Paliativos/métodos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Austrália , Fracionamento da Dose de Radiação , Feminino , Neoplasias Gastrointestinais , Hospitais Privados/estatística & dados numéricos , Hospitais Públicos/estatística & dados numéricos , Humanos , Neoplasias Pulmonares , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos/estatística & dados numéricos , Neoplasias da Próstata , Radioterapia/métodos , Radioterapia/estatística & dados numéricos , Dosagem Radioterapêutica , População Rural/estatística & dados numéricos , Fatores Socioeconômicos , Fatores de Tempo , População Urbana/estatística & dados numéricos
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