Diagnóstico e tratamento dos derrames pleurais malignos / Diagnosis and treatment of malignant pleural effusions

Carcinomas brônquicos, com maior frequência os adenocarcinomas, linfomas e carcinoma de mama, constituem 75% das causas de derrame pleural maligno (DPM). Para utilização das diversas opções terapêuticas paliativas disponíveis deve ser considerada uma avaliação multidisciplinar do estado do paciente, em conjunto com a experiência do profissional médico assistente, a capacidade técnica da instituição onde o tratamento será realizado e o custo-benefício AU.

Lung cancer, more often adenocarcinomas, lymphomas and breast carcinoma, are 75.0% of the causes of malignant pleural effusion. Palliative therapeutic options should be considered a multidisciplinary assessment of the patient's condition, together with the experience of the physician assistant professional, technical capacity of the institution where the treatment will be carried out and cost-effective AU.

Radical pleurectomy/decortication followed by high dose of radiation therapy for malignant pleural mesothelioma. Final results with long-term follow-up.

PURPOSE: We have previously shown the feasibility of delivering high doses of radiotherapy in malignant pleural mesothelioma (MPM) patients who underwent radical pleurectomy/decortication (P/D) or surgical biopsy. In this report, we present the long-term results of MPM patients treated with radical P/D followed by high doses of radiotherapy. METHODS AND MATERIALS: Twenty consecutive MPM patients were enrolled in this prospective study and underwent radical P/D followed by high dose radiotherapy. The clinical target volume was defined as the entire hemithorax excluding the intact lung. The dose prescribed was 50 Gy in 25 fractions. Any FDG-avid areas or regions of particular concern for residual disease were given a simultaneous boost to 60 Gy. Nineteen patients received cisplatin/pemetrexed chemotherapy. Kaplan-Meier analysis was used to calculate rates of overall survival (OS), progression-free survival (PFS), and loco-regional control (LRC). RESULTS: The median follow-up was of 27 months. The median OS and PFS were 33 and 29 months, respectively. The median LRC was not reached. The Kaplan-Meier estimates of OS at 2 and 3 years were 70% and 49%, respectively. The estimates of PFS at 2 and 3 years were 65% and 46%, respectively. The estimates of LRC at 2 and 3 years were 68% and 59%, respectively. The predominant pattern of failure was distant: 7 patients developed distant metastases as the first site of relapse, whereas only 3 patients experienced an isolated loco-regional recurrence. No fatal toxicity was reported. Five Grades 2-3 pneumonitis were documented. CONCLUSIONS: High dose radiation therapy following radical P/D led to excellent loco-regional control and survival results in MPM patients. A median OS of 33 months and a 3-year OS rate of 49% are among the best observed in recent studies, supporting the idea that this approach represents a concrete therapeutic option for malignant pleural mesothelioma.

Computed tomography-guided interstitial high-dose-rate brachytherapy in the local treatment of primary and secondary intrathoracic malignancies.

INTRODUCTION: Image-guided interstitial (IRT) brachytherapy (BRT) is an effective treatment option as part of a multimodal approach to the treatment of isolated lung tumors. In this study, we report our results of computed tomography-guided IRT high-dose-rate (HDR) BRT in the local treatment of inoperable primary and secondary intrathoracic malignancies. METHODS: Between 1997 and 2007, 55 patients underwent a total of 68 interventional procedures for a total of 60 lung lesions. The median tumor volume was 160 cm³ (range, 24-583 cm³). Thirty-seven patients were men and 18 were women, with a median age of 64 years (range, 31-93 years). The IRT-HDR-BRT delivered a median dose of 25.0 Gy (range, 10.0-32.0 Gy) in twice-daily fractions of 4.0 to 15.0 Gy in 27 patients and 10.0 Gy (range, 7.0-32.0 Gy) in once-daily fractions of 4.0 to 20.0 Gy in 28 patients. RESULTS: The median follow-up was 14 months (range, 1-49 months). The overall survival rate was 63% at 1 year, 26% at 2 years, and 7% at 3 years. The local control rate for metastatic tumors was 93%, 82%, and 82% and for primary intrathoracic cancers 86%, 79%, and 73% at 1, 2, and 3 years, respectively. Pneumothoraces occurred in 11.7% of interventional procedures, necessitating postprocedural drainage in one (1.8%) patient. CONCLUSIONS: In patients with inoperable intrathoracic malignancies, computed tomography-guided IRT-HDR-BRT is a safe and effective alternative to other locally ablative techniques.

Salvage radiotherapy for postoperative loco-regional recurrence of esophageal cancer.

The aim of this paper is to evaluate the treatment outcome of radiation therapy (RT) for 16 loco-regionally recurrent esophageal cancer patients. Between 1995 and 2004, patients with loco-regional recurrence of esophageal cancer after curative surgery received RT with or without chemotherapy (CTx) at an average total dose of 56.6 Gy (n = 16, REC group). The site of recurrence was the supraclavicular region in three patients, the mediastinal region in nine patients, and both the supraclavicular and mediastinal regions in four patients. We compared the data with those of patients receiving palliative RT with or without CTx for mediastinal relapse, distant metastasis or malignant pleural effusion (n = 39, META group) and with those of patients receiving postoperative RT with or without CTx in a planned fashion 4-6 weeks after esophagectomy (n = 27, PORT group). The median survival period was 13.8 months in the REC group, 3.5 months in the META group, and 19.1 months in the PORT group. The survival rates at 1 and 2 years were 56% and 19% in the REC group, 6% and 3% in the META group (P = 0.0003), and 70% and 43% in the PORT group (P = 0.1917), respectively. According to univariate analysis, the factor of worse prognosis was not found in the REC group. Complete or partial responses were observed in four (25%) and nine (56%) of the REC group patients, respectively. In the REC group, changes in clinical symptoms, such as dysphagia and recurrent nerve paralysis, could be evaluated in eight patients, and improvement in symptoms was obtained in five (63%) patients. The prognosis of patients who received RT for postoperative loco-regional recurrence of esophageal cancer was significantly better than that of the META group patients and compatible with that of the PORT group patients. Additionally, there is symptomatic relief in a substantial proportion of such patients, and long-term survival is possible in some patients.

Combined intrapleural and intravenous chemotherapy, and pulmonary irradiation, for treatment of patients with lung cancer presenting with malignant pleural effusion. A pilot study.

OBJECTIVES: Patients with non-small-cell lung cancer (NSCLC) and malignant pleural effusion (MPE) are difficult to manage clinically and have a short life expectancy. In this pilot study, we designed a protocol of combined intrapleural (i.p.) and intravenous (i.v.) chemotherapy and pulmonary irradiation to enhance local as well as systemic control of the disease. METHODS: From April 1998 to April 2000, 27 patients with NSCLC and symptomatic MPE were eligible for the study. Patients received pre-radiation chemotherapy (cisplatin 60 mg/m(2) i.p. on day 1; gemcitabine 1,000 mg/m(2) i.v. on days 1, 8, and 15, q4week x 3) after surgical implantation of i.p. and i.v. port-A, followed by radiotherapy (7,020 cGy/39fr), and, finally, post-radiation chemotherapy (docetaxel 60 mg/m(2) q3week x 3-6 i.v.). RESULTS: Grade 1/2 nausea/vomiting and impaired renal function were more common from pre-radiation than post-radiation chemotherapy; however, grade 3/4 toxicities from pre-radiation chemotherapy were minimal. Conversely, grade 3/4 leukopenia and grade 1/2 alopecia, diarrhea, elevation of SGOT/SGPT, and sensory impairment were more common following post-radiation chemotherapy. Only two patients experienced recurrence of pleural effusion. The overall response rate was 55% with 7% complete remission, 48% partial remission, 22% stable disease, and 22% progressive disease. The median failure-free and overall survival was 8 and 16 months, respectively. The one-year survival rate was 63% (95% confidence interval, 45-80%). CONCLUSIONS: We conclude that the combination of i.p. and i.v. chemotherapy and pulmonary irradiation is feasible and should be tested in a larger clinical trial to determine whether survival can be improved for this cohort of patients.

Combination chemotherapy in patients with malignant pleural effusions from non-small cell lung cancer : cisplatin, ifosfamide, and irinotecan with recombinant human granulocyte colony-stimulating factor support.

OBJECTIVES: Malignant pleural effusions develop frequently in patients with non-small cell lung cancer (NSCLC), and the prognosis for these patients is very poor. We evaluated the role of systemic chemotherapy for patients with malignant pleural effusions from NSCLC. METHODS: We analyzed 34 patients who were found to have malignant pleural effusions in the course of diagnosis of 118 patients enrolled in three consecutive clinical trials on advanced NSCLC assessing combination chemotherapy of cisplatin, ifosfamide, and irinotecan with recombinant human granulocyte colony-stimulating factor support. The objective response in the malignant pleural effusion was evaluated by CT scans every course with the response criteria of the Japan Lung Cancer Society. RESULTS: All patients had adenocarcinoma. The pleural effusion showed a complete response in 13 patients, a partial response in 7 patients, and no response in 14 patients. In the assessment of the efficacy of the treatment for the measurable primary or metastatic lesions, there was a partial response in 25 patients, no change in 8 patients, and progressive disease in 1 patient. The response rate in pleural effusions was 58.8%, and overall response in mensurable lesions was 73.5%. The median time to response and duration of response for pleural effusions were 54 days and 151 days, respectively. The median survival time and 1-year survival rates were 362 days and 48.5%, respectively. CONCLUSIONS: Both the response rate and survival data in this retrospective study suggest a high degree of activity of this combination chemotherapy in patients with malignant pleural effusions from NSCLC.

Intrapleurally instilled mitoxantrone in metastatic pleural effusions: a phase II study.

Thirty cases (breast cancer-20 cases, malignant lymphoma-4 cases, different malignancies-6 cases) of histologically/cytologically verified malignant pleural effusion (MPE) in 29 patients were treated with intrapleurally instilled mitoxantrone (30 mg). The therapy was well tolerated. At evaluation, 25 patients had died of progressive disease. The median survival was 3 months (range 0.3-21.3 months). There were 26 responders (12 complete responses (CR), 14 partial responses (PR)), whereas 4 patients relapsed and 3 of these had an early relapse (within 3 months). Patients achieving PR or CR had a low risk (15%) of treatment failure. Five patients were subjected to a pharmacokinetic evaluation. This demonstrated rapidly declining plasma and pleural exudate levels of mitoxantrone within the first 6 hours. At 24 hours after instillation, mitoxantrone was only detected in circulating mononuclear cells. This study shows that mitoxantrone is efficacious in the treatment of MPE, and may represent a cost-effective alternative.

Hypotonic cisplatin treatment for carcinomatous pleuritis found at thoracotomy in patients with lung cancer. In vitro experiments and preliminary clinical results.

We have developed an intraoperative intrapleural treatment with the use of distilled water combined with cisplatin for carcinomatous pleuritis found at thoracotomy in patients with non-small-cell lung cancer. In the in vitro experiment, three different cell lines were used as a model of malignant pleural effusion. Cell growth was examined after a 3-day culture, which was preceded by exposure of the cells to cisplatin in either phosphate-buffered saline solution or distilled water for 1/2 to 5 minutes. The growth inhibition of tumor cells after hypotonic cisplatin treatment was significantly greater than after treatment with saline solution and cisplatin. Tumor that was obtained by resection of non-small-cell lung cancer was used as a model to demonstrate decreased viability of the tumor after exposure to hypotonic cisplatin. The viability of the tumor in a 6-day culture, preceded by exposure to hypotonic cisplatin (50 micrograms/ml) for 10 minutes, was markedly decreased. Intraoperative intrapleural hypotonic cisplatin was instilled in seven patients with pleural carcinomatosis without side effects and with control of pleural dissemination and pleural effusion for 6 to 29 months.

Radiation: an alternative agent for pleurodesis.

Radiotherapy as an alternative agent has been tried for pleurodesis in four proven cases of adenocarcinoma of the lung. This non-invasive technique appears to be beneficial, however, this requires further trials.

[Therapy of pronounced pleural and pericardial effusion in metastatic breast cancer with local mitoxantrone and radiation therapy. Presentation of the intrapleural cytologic findings during this therapy]. / Therapie eines ausgeprägten Pleura- und Perikardergusses bei metastasierendem Mammakarzinom mit lokaler Mitoxantron- und Strahlentherapie. Darstellung des intrapleuralen zytologischen Bildes unter dieser Therapie.

The method of intrapleural Mitoxantrone therapy in case of metastasizing mammary cancer is presented in form of a case report. The uncomplicated procedure, the high rate of remission and the few side effects are the advantages as compared to other methods of pleurodesis. Mitoxantrone could cause an intrapleural inflammatory reaction. That is supported by the cytologic findings before and after the therapy.