RESUMO
OBJECTIVES: To test the efficacy of a natural cytokine mixture (IRX-2), cyclophosphamide, indomethacin, and zinc to induce immune regression of squamous cell carcinoma (SCC) of the head and neck (H&N) prior to conventional therapy and to characterize the responses. PATIENTS AND DESIGN: A phase 2 trial was performed in 15 adults with recently diagnosed, biopsy-confirmed H&N SCC (3 with stage II disease, 6 with stage III disease, and 6 with stage IV disease). The patients were treated with 20 days of perilymphatic injections of IRX-2 (administered subcutaneously at the base of the skull) in combination with contrasuppression consisting of a low-dose infusion of cyclophosphamide (300 mg/m2), and daily oral indomethacin and zinc (StressTabs) in a 21-day cycle before surgery and/or radiotherapy. Tumor dimensions, toxic effects, and disease-free survival were monitored. The tumor sections were histologically examined after surgery, and tumor reduction, fragmentation, and lymphoid infiltration were assessed. RESULTS: All 15 patients responded clinically to the 21-day IRX-2 protocol: 1 with a complete response, 7 with a partial response, and 7 with a minor response. All 15 patients responded pathologically with tumor reduction (mean, 42%) and fragmentation (mean, 50%) in the histological section and increased lymphoid infiltration. The adverse effects of the IRX-2 protocol were negligible except for an allergic skin rash (n = 1) and parotiditis (n = 1). Indomethacin caused gastritis in 1 patient. Reduction of pain and ulceration and bleeding were observed in 8 and 4 patients, respectively. Four of 5 patients with lymphopenia showed increased CD3, CD4, and CD8 cell counts. After surgery (n = 13) and/or radiotherapy (n = 10) and with a mean follow-up of 17 months, 3 patients have had recurrences, 1 patient has died of disease, 1 patient has been re-treated with immunotherapy and has no evidence of disease, and 1 patient is alive with disease. Two patients died of other causes with no evidence of disease. CONCLUSIONS: The IRX-2 immunotherapy induced lymphocyte mobilization and infiltration in H&N SCC associated with clinical and histological tumor responses indicative of immune regression in all 15 patients. Minimal toxic effects were observed, and overall survival may have been improved. A phase 3 trial seems warranted.
Assuntos
Carcinoma de Células Escamosas/terapia , Citocinas/uso terapêutico , Neoplasias de Cabeça e Pescoço/terapia , Imunoterapia/métodos , Terapia Neoadjuvante , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Terapia Combinada , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Citocinas/efeitos adversos , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Indometacina/efeitos adversos , Indometacina/uso terapêutico , Metástase Linfática , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Zinco/efeitos adversos , Zinco/uso terapêuticoAssuntos
Glândula Tireoide/citologia , Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Tireoidite/diagnóstico por imagem , Tireoidite/patologia , Adulto , Biópsia por Agulha/normas , Reações Falso-Negativas , Reações Falso-Positivas , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , UltrassonografiaRESUMO
A direct waveform mean-shape vector quantization (MSVQ) is proposed here as an alternative for electrocardiographic (ECG) signal compression. In this method, the mean values for short ECG signal segments are quantized as scalars and compression of the single-lead ECG by average beat substraction and residual differencing their waveshapes coded through a vector quantizer. An entropy encoder is applied to both, mean and vector codes, to further increase compression without degrading the quality of the reconstructed signals. In this paper, the fundamentals of MSVQ are discussed, along with various parameters specifications such as duration of signal segments, the wordlength of the mean-value quantization and the size of the vector codebook. The method is assessed through percent-residual-difference measures on reconstructed signals, whereas its computational complexity is analyzed considering its real-time implementation. As a result, MSVQ has been found to be an efficient compression method, leading to high compression ratios (CR's) while maintaining a low level of waveform distortion and, consequently, preserving the main clinically interesting features of the ECG signals. CR's in excess of 39 have been achieved, yielding low data rates of about 140 bps. This compression factor makes this technique especially attractive in the area of ambulatory monitoring.
Assuntos
Eletrocardiografia , Processamento de Sinais Assistido por Computador , MatemáticaRESUMO
OBJECTIVE: To induce tumor regression with immunotherapy and to characterize the histology. SETTING: National Institute of Cancerology, Mexico City, Mexico. PATIENTS: Thirteen patients with advanced squamous cell carcinoma of the head and neck region. INTERVENTION: A 21-day cycle of preoperative immunotherapy, including a single intravenous infusion of low-dose cyclophosphamide (300 mg/M2), 10 daily perilymphatic injections of a natural cytokine mixture (approximately 150 units interleukin-2 equivalence by enzyme-linked immunosorbent assay), daily oral indomethacin, and daily oral zinc with multivitamins. OUTCOME MEASURES: Pretreatment biopsies were performed to confirm the diagnosis and to characterize the lesion by standard pathologic criteria, including the degree of tumor-associated lymphocytes. Clinical responses were assessed at surgery, and the specimen was analyzed with respect to changes in tumor morphology and lymphoid and inflammatory infiltration (T and B lymphocytes, plasma cells, macrophages, granulocytes, and giant cells). The presurgical and postsurgical characteristics were ascribed percentages based on a representative section. RESULTS: Prior to treatment, on average the biopsies demonstrated 77% solid tumor with 14% stroma and 9% sparse infiltration of lymphocytes. After treatment, one patient had a complete clinical response and showed only residual inflammatory cells and fibrosis. One patient had no clinical or histologic response. Of the remaining 11 patients, 4 had partial, 6 had minor, and 1 had no response. Tumors were reduced an average of 41% (16% solid and 25% fragmented) and lymphoid infiltration increased to 45% without change in residual stroma. CONCLUSIONS: The pathologic changes viewed in the context of the clinical findings indicate that this immunotherapy protocol induces immune regression of the tumor, mediated predominantly by T and B lymphocytes, and thus elicits a tumor-specific immune reaction.