RESUMO
BACKGROUND AND PURPOSE: To prospectively determine the feasibility, safety, and efficacy of stereotactic body radiation therapy (SBRT) to primary and secondary liver tumors with MR-guided radiation therapy (MRgRT). MATERIALS AND METHODS: Treatment plans with a conventional CT-guided linear accelerator and a MRI-guided tri-60Co teletherapy unit (MR-Co) were generated and compared for patients undergoing liver-directed SBRT from 2015 to 2017. If dosimetric parameters were met on MR-Co, patients were treated with MRgRT. The highest priority constraint was >1000â¯cc or >800â¯cc of normal liver receiving <15â¯Gy for single- or multiple-lesion treatments, respectively. Treatment was delivered every other day. RESULTS: Of 23 patients screened, 20 patients (8 primary, 12 secondary) and 25 liver tumors underwent MR-guided SBRT to a median dose of 54â¯Gy (range 11.5-60) in a median of 3 fractions (range 1-5). With a median follow up of 18.9â¯months, the 1- and 2-year estimate of local control were 94.7% and 79.6%, respectively. A difference in local control between single and multiple lesions or BEDâ¯≥â¯100â¯Gy10 and BEDâ¯<â¯100â¯Gy10, respectively, was observed. The 2-year estimate of overall survival (OS) was 50.7% with a median OS of 29â¯months. There were no acute gradeâ¯≥â¯3 toxicities and one late grade 3/4 toxicity from a single patient whose plan exceeded an unrecognized dose constraint at the time. CONCLUSION: MR-guided SBRT is a viable and safe option in the delivery of ultrahypofractionated ablative radiation treatment to primary and secondary liver tumors resulting in high rates of local control and very favorable toxicity profiles.
Assuntos
Neoplasias Hepáticas , Radiocirurgia , Radioterapia Guiada por Imagem , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/radioterapia , Imageamento por Ressonância Magnética/métodos , Estudos Prospectivos , Radiocirurgia/métodos , Radioterapia Guiada por Imagem/efeitos adversos , Radioterapia Guiada por Imagem/métodosRESUMO
PURPOSE: In a single-institution phase II study, we evaluated the safety of a 5-day dose-equivalent neoadjuvant radiotherapy (RT) regimen for high-risk primary soft tissue sarcoma. PATIENTS AND METHODS: Patients received neoadjuvant RT alone (30 Gy in five fractions) to the primary tumor with standard margins. The primary endpoint was grade ≥2 late-radiation toxicity. Major wound complications, local recurrences, and distant metastases were also examined. In exploratory analysis, we evaluated germline biomarkers for wound toxicity and the effects of the study on treatment utilization. RESULTS: Over 2 years, 52 patients were enrolled with median follow-up of 29 months. Seven of 44 evaluable patients (16%) developed grade ≥2 late toxicity. Major wound complications occurred in 16 of 50 patients (32%); a signature defined by 19 germline SNPs in miRNA-binding sites of immune and DNA damage response genes, in addition to lower extremity tumor location, demonstrated strong predictive performance for major wound complications. Compared with the preceding 2-year period, the number of patients treated with neoadjuvant RT alone at our institution increased 3-fold, with a concomitant increase in the catchment area. CONCLUSIONS: A shorter 5-day neoadjuvant RT regimen results in favorable rates of wound complications and grade ≥2 toxicity after 2-year follow-up. Five-day RT significantly increased utilization of neoadjuvant RT at our high-volume sarcoma center. With further validation, a putative germline biomarker for wound complications may guide safer RT utilization.
Assuntos
MicroRNAs/genética , Terapia Neoadjuvante/métodos , Polimorfismo de Nucleotídeo Único/genética , Dosagem Radioterapêutica/normas , Sarcoma/radioterapia , Neoplasias de Tecidos Moles/radioterapia , Ferimentos e Lesões/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Sarcoma/patologia , Neoplasias de Tecidos Moles/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Several single center studies have provided evidence of immune activation and antitumor activity of therapeutic vaccination with dendritic cells (DC) in patients with metastatic melanoma. The efficacy of this approach in patients with favorable prognosis metastatic melanoma limited to the skin, subcutaneous tissues and lung (stages IIIc, M1a, M1b) was tested in a multicenter two stage phase 2 study with centralized DC manufacturing. METHODS: The vaccine (IDD-3) consisted 8 doses of autologous monocyte-derived matured DC generated in serum-free medium with granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-13 (IL-13), pulsed with lysates of three allogeneic melanoma cell lines, and matured with interferon gamma. The primary endpoint was antitumor activity. RESULTS: Among 33 patients who received IDD-3 there was one complete response (CR), two partial responses (PR), and six patients had stable disease (SD) lasting more than eight weeks. The overall prospectively defined tumor growth control rate was 27% (90% confidence interval of 13-46%). IDD-3 administration had minimal toxicity and it resulted in a high frequency of immune activation to immunizing melanoma antigens as assessed by in vitro immune monitoring assays. CONCLUSIONS: The administration of matured DC loaded with tumor lysates has significant immunogenicity and antitumor activity in patients with limited metastatic melanoma. CLINICAL TRIAL REGISTRATION: NCT00107159.
Assuntos
Vacinas Anticâncer/administração & dosagem , Células Dendríticas/citologia , Melanoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Vacinas Anticâncer/efeitos adversos , Vacinas Anticâncer/uso terapêutico , Linhagem Celular Tumoral , Feminino , Citometria de Fluxo , Humanos , Interferon gama/metabolismo , Proteína 1 de Membrana Associada ao Lisossomo/metabolismo , Proteína 2 de Membrana Associada ao Lisossomo/metabolismo , Masculino , Melanoma/metabolismo , Melanoma/patologia , Pessoa de Meia-Idade , Metástase Neoplásica , Resultado do TratamentoRESUMO
Alpha-fetoprotein (AFP) is a self protein expressed by fetal liver at high levels, but is transcriptionally repressed at birth. AFP is up-regulated in hepatocellular carcinomas, and patients with active disease could have plasma levels as high as 1 mg/mL. We previously identified four immunodominant HLA-A*0201-restricted peptides [hAFP(137-145) (PLFQVPEPV), hAFP(158-166) (FMNKFIYEI), hAFP(325-334) (GLSPNLNRFL), and hAFP(542-550) (GVALQTMKQ)] derived from human AFP that could stimulate specific T cell responses in healthy donor peripheral blood lymphocytes in vitro. We conducted a phase I/II clinical trial in which HLA-A*0201 patients with AFP-positive hepatocellular carcinoma were immunized with three biweekly intradermal vaccinations of the four AFP peptides pulsed onto autologous dendritic cells (DC). DCs were prepared from adherent peripheral blood mononuclear cells cultured with granulocyte-macrophage colony-stimulating factor and interleukin-4 for 7 days. Sixteen subjects were enrolled and 10 were treated. Peripheral blood lymphocytes were isolated from these patients before, during, and after AFP peptide/DC immunization and were tested ex vivo with MHC tetramer and IFNgamma ELISPOT analysis. Six of 10 subjects expanded statistically significant levels of AFP-specific T cells postvaccine to at least one peptide by MHC tetramer. Also, 6 of 10 subjects increased IFNgamma producing AFP-specific T cell responses to at least one of the peptides postvaccination, by ELISPOT. We conclude that the human T cell repertoire is capable of responding to the AFP self antigen after the administration of AFP peptide-pulsed DC even in an environment of high circulating levels of this oncofetal antigen.