Beta Blockers with Statins May Decrease All-Cause Mortality in Patients with Cardiovascular Diseases and Locally Advanced Unresectable Non-Small-Cell Lung Cancer after Chemoradiotherapy.

The study was conducted in the era when maintenance immunotherapy with durvalumab was not available in clinical practice after chemoradiotherapy (CRT) in unresectable non-small-cell lung cancer (NSCLC). The main aim of the study was to check whether the presence of cardiovascular diseases (CVD) and their pharmacotherapy affects the overall survival (OS) in such NSCLC patients undergoing sequential CRT. The group of 196 patients were analyzed: 101 patients with CVD (51.53%) and 95 patients with other reasons of qualification for sequential CRT (decreased performance status, older age, and other non-cardiovascular co-morbidities). Although patients with CVD were more often in older age, and they more often experienced cardiac and nephrological complications (p < 0.05 for all), there was a statistically nonsignificant trend for lower all-cause mortality in patients with CVD. The lowest all-cause mortality was observed in patients treated with beta-blockers and statins after two (HR = 0.31; 95%CI: 0.1-0.98; p = 0.047), three (HR = 0.33; 95%CI: 0.13-0.81; p = 0.015) and even four (HR = 0.45; 95%CI: 0.22-0.97; p = 0.027) years of follow-up. The benefit in OS remained significant in 101 patients with CVD treated with beta-blockers (HR = 0.65; 95%CI: 0.43-0.99; p = 0.045), and eventually statin, throughout the whole follow-up (log-rank p < 0.05). Further prospective studies are necessary to confirm the role of beta-blockers and statins in reduction of mortality in NSCLC patients undergoing radical CRT.

Performance-Status Deterioration during Sequential Chemo-Radiotherapy as a Predictive Factor in Locally Advanced Non-Small Cell Lung Cancer.

The role of sequential chemoradiotherapy in non-small cell lung cancer (NSCLC) patients who are not eligible for concurrent therapy has not been clearly defined. The aim of this study was to determine the usefulness of Karnofsky performance status (KPS) monitoring and to define the factors determining clinical deterioration during sequential chemoradiotherapy in patients treated from July 2009 to October 2014. The study included 196 patients. The clinical stage was defined as III A in 94 patients (48%) and III B in 102 patients (52%). Reduced KPS was found in 129 patients (65.8%). Baseline KPS had no significant prognostic significance. Deterioration of KPS during chemoradiotherapy was observed in 53 patients (27%) and had a negative predictive value for both worse-progression free survival (HR = 1.44; 95% CI: 1.03-1.99; p = 0.03) and overall survival (HR = 1.42; 95% CI: 1.02-1, 99; p = 0.04). The deterioration of KPS correlated with the disease control rate 6 weeks after the end of chemoradiotherapy (p = 0.0085). The risk of KPS worsening increased with each subsequent day between the end of chemotherapy and the start of radiotherapy (OR = 1.03; 95%CI: 1.01-1.05; p = 0.001), but decreased with each year of older age of patients (OR = 0.94, 95% CI: 0.9-0.98, p = 0.009). The time between the end of chemotherapy and the start of radiotherapy determined the prognosis of NSCLC after chemoradiotherapy. It should be adjusted to the age of patients.

A case of adenoid cystic carcinoma of trachea: treatment complications and radiotherapy role.

PURPOSE: Adenoid cystic carcinoma (ACC) of trachea is a relatively rare malignant neoplasm, for which there is a lack of prospective clinical trials investigating treatment effectiveness. Most of the authors prefer surgical resection followed by post-operative radiation therapy in case of incomplete excision. There are no available prospective data on post-relapse treatment. CASE PRESENTATION: The current paper presents a case of tracheal ACC in a young woman, treated solely with surgical resection without radiotherapy due to postoperative neurological complications requiring additional diagnostics, management, and treatment. As a complication itself, spinal cord dysfunction after tracheal surgery is extremely rare, in which radical radiotherapy and brachytherapy were successfully administered after disease recurrence. CONCLUSIONS: Lack of post-operative radiotherapy resulting from neurological complications could be a reason for ACC recurrence in our patient. Administration of radiotherapy after incomplete resection of recurrent disease may lead to long-term locoregional control.

Oral vinorelbine and cisplatin as first-line therapy for advanced squamous NSCLC patients: a prospective randomized international phase II study (NAVoTrial 03).

OBJECTIVE: The study investigated the efficacy and safety of oral vinorelbine-cisplatin (OV-CDDP) and gemcitabine-cisplatin (GEM-CDDP) in patients with squamous non-small cell lung cancer (sq-NSCLC). PATIENTS AND METHODS: This was an open-label, prospective, multicenter, international phase II study that enrolled untreated patients with advanced sq-NSCLC. Patients were randomized to receive 3-week cycles of either 60-80 mg/m2 OV days 1 and 8 in combination with 80 mg/m2 CDDP day 1 (arm A) or 1250 mg/m2 GEM days 1 and 8 in combination with 75 mg/m2 CDDP day 1 (arm B). After four cycles, patients without disease progression continued maintenance dose of OV or GEM until progression or unacceptable toxicity. The primary objective was disease control rate (DCR). Secondary objectives included progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS), safety, and quality of life (QoL). RESULTS: A total of 114 patients with sq-NSCLC were randomized, and 113 were treated (57 in arm A and 56 in arm B). DCR was high in both arms: 73.7% (95%CI: 62.4-100.0) in arm A and 75.0% (95%CI: 63.7-100.0) in arm B. Median PFS and TTF were similar in arm A and B 4.2 and 2.8 months, and 4.3 and 3.1 months, respectively. Even though the difference was not significant, the OS was 10.2 for arm A and 8.4 months for arm B. The safety profiles were consistent with the current knowledge of adverse events. QoL results revealed an improvement in patients under OV treatment. CONCLUSION: The OV-CDDP combination showed comparable efficacy to GEM-CDDP with acceptable safety profile and enhanced patients' QoL. TRIAL REGISTRATION: The study was registered under EudraCT number 2012-003531-40.

Two neoplasms rich in small lymphocytes, B1B2 thymoma and small lymphocytic lymphoma, intermingled in one tumor mass. A case report.

We present a case of a 52-year-old man with myasthenia gravis and a mediastinal tumor who was admitted to our hospital for surgical treatment. The pathologic examination of the resected tumor revealed a very rare case of a collision tumor: a B1B2 thymoma and a small lymphocytic lymphoma. Flow cytometry of the peripheral blood revealed the presence of a small number of leukemic cells. After postoperative irradiation of the mediastinum and chemotherapy a complete response in both diseases was achieved. The case confirms that a pathologist should always be aware that two different neoplasms can coexist in rare cases.

Analysis of treatment results in primary germ cell tumours with mediastinal location: own experience.

INTRODUCTION: Primary germ cell tumours with mediastinal location comprise 1-6% of mediastinal tumours and 2-5% of all germ cell tumours occurring in adults. They are identified mostly in the 3rd decade of life, in 90% of cases in men. The most common symptoms are dyspnea, chest pain, cough, fever and weight loss. The aim of the present study was the analysis of our own results of treatment of primary germ cell tumours with mediastinal location, and a review of the literature concerning this subject. MATERIAL AND METHODS: Five patients (4 males, 1 female) median age 27.8 years (range 23-30 years) treated in the period from 1999 to 2009 in Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Department of Lung Cancer and Chest Tumours in Warsaw, due to germinal tumours with primary mediastinal location, entered the study. RESULTS: All patients received chemotherapy according to the BEP regimen. All patients achieved an objective response to treatment. Two patients died due to disease progression in spite of II- and III-line treatment. Three patients are still in follow-up. The median survival time was 55.8 months (range 8.0-120.0 months). CONCLUSIONS: Primary mediastinal germ cell tumours have worse prognosis than do those with gonadal location. Based on our observations and review of the literature, it can be concluded that the results of treatment of non-seminoma type germ cell tumours with primary mediastinal location remain poor. Patients who develop early recurrence or progression during first-line chemotherapy are particularly at risk of unfavourable outcome. Identification of new standards of treatment in tumours resistant to cisplatin require further studies evaluating the effectiveness of new generation cytostatic drugs.

Prognostic value of synaptophysin and chromogranin a expression in patients receiving palliative chemotherapy for advanced non-small-cell lung cancer.

BACKGROUND: Chemotherapy is the principal treatment method for patients with advanced non-small-cell lung cancer (NSCLC). Treatment with platinum-based and novel chemotherapeutic regimens, compared to monotherapy, slightly increases the response rates to 20-40%. The predictive and prognostic values of molecular factors are highly variable; however, data on clinical-demographic factors are still burdened by significant limitations. OBJECTIVES: The aim of this study was to assess the prognostic value of synaptophysin and chromogranin A protein expression in patients receiving palliative chemotherapy for advanced NSCLC. METHODS: The study population consisted of 23 women and 116 men. The median age was 57.3 years. Expression of synaptophysin and chromogranin was assessed using a two-step model of immunohistochemical staining. Level 0 represented lack of activity, while level 1 represented its expression. RESULTS: Expression of synaptophysin and chromogranin A was observed in 12 (8.6%) and 5 (3.6%) patients, respectively. The risk of death was significantly lower in patients with expression of synaptophysin (p = 0.008) and chromogranin A (p = 0.014). The 12- and 24-month survival rate of patients with synaptophysin expression was 64% (95% CI 0.35-0.93), while for patients without expression it was 46% (95% CI 0.36-0.56) and 16% (95% CI 0.07-0.25), respectively. The 12- and 24-month survival rate of patients with chromogranin expression was 80% (95% CI 0.44-1.00), while for chromogranin A-negative patients it was 47% (95% CI 0.37-0.57) and 19% (95% CI 0.10-0.28), respectively. We did not observe associations between expression of synaptophysin and chromogranin A and the other typical prognostic factors. CONCLUSIONS: Expression of synaptophysin and chromogranin A was associated with a longer median overall survival and might have prognostic value. These results should be confirmed in a prospective study.

[Gefitinib in patients with advanced non-small-cell lung cancer]. / Gefitynib u chorych na niedrobnokomórkowego raka pluca w zaawansowanym stadium.

INTRODUCTION: Patients with advanced non-small cell lung cancer (NSCLC) have a very poor prognosis. Individualization of treatment and identification of therapeutic molecular targets may improve outcomes. Gefitinib was introduced recently among several other molecular-targeted drugs of activity in NSCLC. Gefitinib is indicated for patients diagnosed with advanced or disseminated NSCLC with an activating mutation in the EGFR (epidermal growth factor receptor) gene. The paper summarize experience with gefitinib in the Department of Lung and Thoracic Tumors of Maria Sklodowska-Curie Memorial Cancer Centre and Institute in Warsaw. MATERIAL AND METHODS: The group of 11 patients diagnosed with advanced NSCLC and activating mutations in the EGFR gene was analyzed. Patients were treated from April 2010 to April 2011. Tolerability, objective response rate (ORR) and progression free survival (PFS), which was calculated by the Kaplan-Meier method, were assessed. RESULTS: Median observation time from the start of gefitinib treatment was 14 months (range 4,8-19 months). The rate of one-year survival in this group of patients was 91% (10 patients) with 54% of patients (6 patients) surviving one year without progression of disease. The ORR rate of 82% and median PFS 11.4 months were reached. No treatment-related deaths were reported. Among the complications skin toxicity (82%) and diarrhea (45%) were most frequently observed, in most cases the Common Toxicity Criteria for Adverse Events (CTCAE) first grade. CONCLUSIONS: The results confirm the literature data on the efficacy and safety profile of gefitinib in the treatment of patients with the diagnosis of advanced NSCLC and activating mutation in the EGFR gene.

The qualification of docetaxel or erlotinib for second-line therapy should be based on clinical and molecular predictive factors.

BACKGROUND: We evaluated the effectiveness of docetaxel or erlotinib in second-line treatment of non-small cell lung cancer (NSCLC) and focused on the impact of predictive factors on the outcome of therapy. METHODS: 204 patients with progressive disease after platinum-based therapy were enrolled: 102 received an infusion of 75 mg/m(2) of docetaxel and 102 received 150 mg of erlotinib orally. RESULTS: Response rate (RR) was 6.9 and 8.8% for docetaxel and erlotinib, respectively. Progression-free survival (PFS) was 1.2 months for docetaxel and 1.6 months for erlotinib (hazard ratio, HR = 1.2, p = 0.17). Overall survival was 5.5 versus 7 months for docetaxel and erlotinib, respectively (HR = 1.35, p = 0.06). Using Cox regression, we found clinical factors (performance status and weight loss) with predictive values for RR and PFS in second-line-treated patients. Prior radiotherapy, smoking status and EGFR mutation might help to predict outcome of erlotinib treatment and ßIII-tubulin mRNA expression that of docetaxel, but histopathological diagnosis did not have any predictive value. CONCLUSIONS: Erlotinib and docetaxel show similar efficacy in the treatment of NSCLC. The application of predictive factors may facilitate qualification for second-line treatment with both drugs.

Erlotinib in salvage treatment of patients with advanced non-small cell lung cancer: results of an expanded access programme in Poland.

AIM OF THE STUDY: Erlotinib and gefitinib are reversible EGFR-TKI administered orally. Results of the phase III study JBR.21 proved the clinical efficacy of erlotinib-based regimens as second- or third-line treatment of advanced NSCLC. We analyze efficacy of treatment with erlotinib in patients suffering from advanced stage NSCLC who participated in the multicentre, international phase IV study - MO 18109 TRUST (expanded access clinical program of Tarceva™ in patients with advanced stage IIIB/IV NSCLC). Our analysis was performed based on clinical data derived from centres with the largest number of patients who received erlotinib. MATERIAL AND METHODS: Between May and November 2005, a total of 56 patients (19 women and 37 men) with histologic or cytologic diagnosis of NSCLC were included in the study. The histological diagnosis was: squamous-cell (n = 23), adenocarcinoma (n = 20), broncho-alveolar carcinoma (n = 2). In 11 patients the type of NSCLC was not specified. RESULTS: Patients received erlotinib in a single dose of 150 mg per day. Partial response (PR), stable disease (SD) or progressive disease (PD) were observed in 5 (9%), 33 (59%) and 16 (29%) patients respectively. Median PFS was 16.0 weeks. In the study population adverse events (AE) were noted in 12 (21%) patients. CONCLUSIONS: Results of the TRUST study in the Polish population confirmed the efficacy of erlotinib in advanced NSCLC after failure of prior platinum-based chemotherapy. Treatment with erlotinib was associated with longer PFS as compared to the JBR.2 study, whole TRUST study population and Italian population included in the TRUST study.