Invasive methods for the diagnosis and management of intrathoracic extramedullary hematopoiesis: A literature review.

BACKGROUND: Extramedullary hematopoiesis is defined as hematopoiesis occurring outside of the bone marrow. It usually compensates insufficient bone marrow function or ineffective erythropoiesis and is observed mostly in hematological disorders. Most common locations of extramedullary hematopoiesis are the spleen, the liver and the lymph nodes. Intrathoracic extramedullary hematopoiesis is rare presenting as bilateral lobulated masses of lower paravertebral regions. This review summarizes the role of invasive techniques in the diagnosis and management of intrathoracic EMH and its complications. METHODS: An electronic search in PubMed and Google Scholar was conducted with the keywords "intrathoracic extramedullary hematopoiesis" AND "surgery" OR "video-assisted thoracic surgery (VATS)" OR "medical thoracoscopy" OR "biopsy" OR "thoracotomy" OR "image-guided biopsy" OR "median sternotomy", within 1970 to 2020 with the limitation of English language to include those articles reporting data on invasive techniques in intrathoracic extramedullary hematopoiesis. RESULTS: Overall, 93 articles were originally identified using our search criteria and from the reference list of the previously identified documents. Following elimination of duplicates, 29 were excluded after title, abstract or full text screening, since they did not report the use of invasive techniques in the diagnosis and management of intrathoracic extramedullary hematopoiesis. CONCLUSIONS: Although in some cases radiological features are typical for the diagnosis of intrathoracic extramedullary hematopoeisis, invasive methods such as bronchoscopy with transbronchial biopsy, ιmage-guided fine needle aspiration, endobronchial ultrasound-guided fine needle aspiration of the mass and mediastinoscopy, medical thoracoscopy, median sternotomy, video-assisted thoracoscopic surgery and thoracotomy, are essential for definite diagnosis and management.

Comparison of docetaxel/cisplatin to docetaxel/gemcitabine as first-line treatment of advanced non-small cell lung cancer: early results of a randomized trial.

The study compares docetaxel plus cisplatin (DC) and docetaxel plus gemcitabine (DG) regimens for the treatment of advanced non-small cell lung cancer (NSCLC). Patients were randomized to receive either the DC or the DG combination. They were stratified according to age, performance status (PS) and stage of disease. Three hundred seventeen patients entered the study. Of them, 162 received the DC regimen and 155 the DG regimen. There were no differences in the patients' characteristics between the two study arms. Preliminary analysis included 132 evaluable patients in the DC arm and 114 in the DG arm. Three complete responses (CR) (2.3%) and 39 partial responses (PR) (30%) were documented in the DC arm (response rate (RR) 32.3%; 95% CI 23.87-39.76%), whereas 1 CR (0.9%) and 38 PR (33%) were documented in the DG arm (RR: 33.9%; 95% CI 25.5-42.92%). No differences in the RR, response duration, time to tumor progression, overall survival and 1-year survival were observed between the two groups. Regarding toxicity, there were no significant differences in grade 3-4 anaemia and thrombocytopenia between the two arms. However, grade 3-4 neutropenia occurred in 40 patients (33%) treated with the DC regimen and in 31 patients (22%) treated with the DG regimen (P=0.01). Twenty-four (16%) patients in the DC arm and 20 (14%) in the DG arm developed febrile neutropenia. There was one death due to sepsis in each arm. Non-haematological toxicity was mild and equal in the two arms, with the exception of grade 3-4 nausea and diarrhoea, which were more frequent in the DC arm. In conclusion, preliminary results showed that the DG regimen was as effective as the DC regimen. The toxicity profile of the DG combination was relatively milder. Hence, cisplatin cannot be considered longer as a mandatory component of chemotherapy against NSCLC.

Second-line treatment with vinorelbine and carboplatin in patients with advanced non-small cell lung cancer. A multicenter phase II study.

OBJECTIVE: A phase II study was conducted to evaluate the efficacy and toxicity of vinorelbine-carboplatin (VNB-C) combination as a salvage treatment in patients with advanced non-small cell lung cancer (NSCLC) progressing after or failing previous non-platinum, taxane-based treatment. PATIENTS AND METHODS: Thirty-seven patients with cytologically or histologically confirmed NSCLC were enrolled. VNB 30 mg/m(2) was administered on days 1 and 8 and C 300 mg/m(2) on day 1 every 28 days. G-CSF (5 microg/kg per day s.c.) was used prophylactically on days 10-15 in case of grade 3-4 neutropenia or febrile neutropenia after the first cycle. RESULTS: Twenty-nine patients were evaluable for response and all were evaluable for toxicity. In an intention-to-treat analysis, two (5%) complete and four (11%) partial responses were documented for an overall response rate of 16% (95% CI, 4.49-28.84%). Eleven (30%) patients experienced disease stabilisation and 20 (54%) disease progression. The median duration of response was 7.5 months, the median TTP was 9 months, and the median survival was 8.5 months. Patients with objective remission and stable disease had a statistically significant survival benefit over patients with disease progression. Grade 3 and 4 neutropenia occurred in three (8%) and ten (27%) patients, respectively, and six cases (16%) were complicated with fever. Grade 4 thrombocytopenia was documented in one (3%) patient. Non-hematological toxicity was mild, with grade 2 and 3 asthenia reported in 18 (48%) patients. No treatment-related deaths occurred. CONCLUSION: VNB-C combination is well tolerated and retains a notable degree of activity in NSCLC patients progressing after previous non-platinum, taxane-based treatment. Moreover, it confers tumour growth control in a significant proportion of patients, and this seems to be associated with a survival benefit for them.

A multicenter randomized clinical trial comparing paclitaxel-cisplatin-etoposide versus cisplatin-etoposide as first-line treatment in patients with small-cell lung cancer.

BACKGROUND: Previous phase I-II studies have shown that the combination of paclitaxel-cisplatin-etoposide (TEP) is very active and well tolerated in patients with small-cell lung cancer (SCLC). In order to compare the TEP combination to cisplatin etoposide (EP) regimen as front-line treatment in patients with SCLC, we conducted a randomised multicenter study. PATIENTS AND METHODS: One hundred thirty-three chemotherapy-naïve patients with histologically proven limited or extensive stage SCLC were randomised to receive either paclitaxel 175 mg/m2 i.v. three-hour infusion on day 1 and cisplatin 80 mg/m2 i.v. on day 2 and etoposide 80 mg/m2 i.v. on days 2-4 with G-CSF support (5 mcg/kg s.c. days 5-15) or cisplatin 80 mg/m2 i.v. on day 1 and etoposide 120 mg/m2 i.v. on days 1-3 in cycles every twenty-eight days. RESULTS: Due to excessive toxicity and mortality observed in the TEP arm, an early interim analysis was performed and the study was closed. Sixty-two patients received two hundred sixty-one cycles of TEP and seventy-one patients three hundred twenty-three cycles of EP The two patient groups were well balanced for age, sex, performance status, stage of disease and the presence of abnormal LDH at diagnosis. In an intention-to-treat overall analysis both regimens were equally active with a complete and partial response rate of 50% (95% confidence interval (CI): 37.5%-62.4%) for TEP and 48% (95%) CI: 36.2%-59.5%) for EP (P = 0.8). The median time to disease progression was 11 months for TEP and 9 months for EP (P = 0.02). The duration of response, one-year survival and overall survival were similar in the two arms. Similarly, in an intention-to-treat subgroup analysis of patients with limited or extensive stage disease, there was no difference in the activity between the two regimens except of a longer median time to disease progression in the extensive stage in favour of the TEP regimen, eight versus six months (P = 0.04). However, there were eight toxic deaths in the TEP arm versus none in the EP arm (P = 0.001). Moreover, the TEP regimen was associated with more severe toxicity than the EP regimen in terms of grade 4 neutropenia (P = 0.04), grade 3-4 thrombocytopenia (P = 0.02), febrile neutropenia (P = 0.08), grade 3-4 diarrhea (P = 0.01), grade 3-4 asthenia (P = 0.05) and grade 3 neurotoxicity (P = 0.06). CONCLUSIONS: In this early terminated study, the TEP regimen was significantly more toxic than the EP regimen. The TEP regimen is associated with significant toxicity and mortality, and should not be used outside of a protocol setting. For future investigations, dose and schedule modifications are necessary to reduce toxicity.

Vinorelbine-based regimens as salvage treatment in patients with advanced non-small cell lung cancer: two parallel multicenter phase II trials.

UNLABELLED: Two parallel phase II trials were conducted in order to evaluate the efficacy and toxicity of vinorelbine-ifosfamide (VNB-IFX) and vinorelbine-carboplatin (VNB-C) combinations as salvage treatment in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients failing platinum-based front-line chemotherapy were enrolled in the VNB-IFX trial while patients failing non-platinum-containing chemotherapy were treated with VNB-C. Twenty-nine patients were treated with VNB-IFX [median age: 59 years; performance status, PS (WHO) 0--1: 72% and disease stage IV: 79%] and 37 with VNB-C [median age: 61 years; PS (WHO) 0--1: 51% and stage IV: 84%]. Patients received vinorelbine 25 mg/m(2) i.v. on days 1 and 8 and ifosfamide 1.6 g/m(2) i.v. on days 8--10 with uroprotective mesna, in cycles of 28 days. G-CSF (5 microg/kg/day s.c.) was administered prophylactically on days 11--16 or until hematological recovery. The VNB-C regimen consisted of carboplatin 300 mg/m(2) on day 1 and vinorelbine 30 mg/m(2) on days 1 and 8 every 28 days. RESULTS: Twenty-six patients were evaluable for response in the VNB-IFX trial and 29 in the VNB-C. Overall response rates (intent-to-treat analysis) were 3% (1 patient; duration of response: 3 months) for the VNB-IFX and 16% (median duration of response: 7.5 months) for the VNB-C combination. The median time to progression and survival for patients receiving VNB-IFX were 4.5 and 6 months (1-year survival: 19%), respectively; the corresponding values for VNB-C were 9.0 and 8.5 months (1-year survival: 38%). The median survival of patients achieving stable disease was 10 (VNB-IFX) and 14.5 (VNB-C) months. Grade 3--4 neutropenia occurred in 4 (13%) of the patients treated with VNB-IFX; all cases were complicated with fever. Grade 3--4 neutropenia was documented in 13 (35%) patients in the VNB-C trial; 6 (16%) developed neutropenic fever. There were no treatment-related deaths. Non-hematologic toxicity for the VNB-IFX and VNB-C regimens was mild with grade 2--3 peripheral neurotoxicity occurring in 3 (10%) and 7 (19%) patients, and grade 2--3 asthenia in 11 (38%) and 18 (48%) patients, respectively. CONCLUSION: Both combinations were associated with a tolerable toxicity profile. VNB-C demonstrated notable activity in patients previously treated with a taxane-based regimen, whilst VNB-IFX failed to produce a significant response rate in patients treated with platinum-containing chemotherapy. Stabilization of disease was associated with a favorable survival in both studies.

Platinum-based and non-platinum-based chemotherapy in advanced non-small-cell lung cancer: a randomised multicentre trial.

BACKGROUND: Docetaxel in combination with cisplatin or gemcitabine are active chemotherapy reigimes against non-small-cell lung cancer. We compared the efficacy and safety of a combination of cisplatin and docetaxel (group 1) with that of gemcitabine and docetaxel (group 2) in the treatment of advanced non-small-cell lung cancer in a prospective, randomised, multicentre trial. METHODS: Patients with stage IIIB or IV lung cancer who had not had prior chemotherapy were allocated either to group 1 and treated with docetaxel (100 mg/m(2), day 1) and cisplatin (80 mg/m(2), day 2) or to group 2 and treated with gemcitabine (1100 mg/m(2), days 1 and 8) and docetaxel (100 mg/m(2), day 8). All patients received recombinant human granulocyte colony-stimulating factor (150 mg/m(2)). All patients received recombinant human granulocyte colony-stimulating factor (150 mg/m(2)) had appropriate standard premedication. Response and toxicity were assessed using WHO criteria. Analysis was by intention to treat. FINDINGS: 441 patients were randomly assigned to receive docetaxel/cisplatin (group 1, n=219) or gemcitabine/docetaxel (group 2, n=222). 14 patients in group 1 and 21 patients in group 2 were not evaluable. Objective response rates were similar in the two groups: group 1, 32.4% (95% CI 26.2-38.6%; 1.4% complete response and 31% partial response); group 2, 30.2% (24.5-36.2%; 0.9% complete response and 29.3% partial response). The two groups did not differ in median duration of response, time to tumour progression, overall survival, or 1 year or 2 year survival rates. INTERPRETATION: Both drug combinations had comparable activity in patients with advanced cancer who had not previously had chemotherapy; however, gemcitabine and docetaxel had the most favourable toxicity profile.

Docetaxel in combination with gemcitabine plus rhG-CSF support as second-line treatment in non-small cell lung cancer. A multicenter phase II study.

BACKGROUND: Docetaxel in combination with gemcitabine is an active front-line chemotherapy regimen against non-small cell lung cancer (NSCLC) with acceptable toxicity. A multicenter phase II study was conducted in order to determine the toxicity and efficacy of this combination, as salvage treatment in patients progressing after a cisplatin-based front line regimens. PATIENTS AND METHODS: Thirty-two patients with histologically confirmed, bidimensionally measurable NSCLC, who failed prior cisplatin-based chemotherapy were enrolled. The patients' median age was 62.5 years, 29 (91%) were male, 23 (72%) had disease stage IV, and 22 (69%) had a performance status (WHO) 0-1. Gemcitabine (900 mg/m(2)) was administered on days 1 and 8 and docetaxel (100 mg/m(2)) on day 8, after appropriate premedication. rhG-CSF (150 microg/m(2)) was given prophylactically from day 9 to 15. Treatment was repeated on an outpatient basis every three weeks. RESULTS: A total of 127 chemotherapy cycles were administered. In an intention-to-treat analysis five patients (15.6%; 95% CI: 3.04-28.21%) achieved a partial response, 11 (34.4%) stable disease, and 16 (50%) progressive disease. The median duration of response was 9 months, the median TTP 7 months, and the overall median survival 6.5 months; the overall 1-year survival probability was 27.6%. Grade 3/4 neutropenia was observed in five (15.6%) patients and in two of them associated with fever. Grade 3 anemia and thrombocytopenia occurred in three (9%) and two (6.5%) patients, respectively. Non-hematologic toxicity was very mild with only one episode of grade 4 diarrhea and mucositis, respectively; two (6%) patients complained for grade 3 asthenia. CONCLUSION: The combination of gemcitabine and docetaxel with prophylactic use of rhG-CSF is a safe and well-tolerated regimen for the treatment of patients with advanced NSCLC, who failed front-line treatment with cisplatin-based regimens.