Decade of lung cancer in Serbia: tobacco abuse and gender differences.

OBJECTIVE: Lung cancer (LC) is one of the most frequently diagnosed cancers and the leading cause of cancer mortality worldwide. The aim of this study was to get a comprehensive insight into the epidemiology of LC among patients in Vojvodina, the Northern Serbian region, during the ten-year period. PATIENTS AND METHODS: This retrospective study was performed using LC hospital registry data of the Institute for Pulmonary Diseases of Vojvodina (IPBV) from 2011 to 2020. All patients reported in the registry with a place of residence in Vojvodina were included in this study. The data used in this research were: date of diagnosis, gender, age at diagnosis, place of residence, smoking habits at diagnosis, the intensity of smoking (pack/years), ECOG performance (0-5), histological cancer type, TNM classification and disease stage. RESULTS: A total of 12,055 LC patients were included, 69.6% of whom were male. The percentage of female LC patients significantly increased, from 26.9% in 2011 to 35.9% in 2020 (p<0.001). Non-small cell lung cancer (NSCLC) was diagnosed in 80.8% of patients, while 15.4% of patients had small cell lung cancer (SCLC). The most common histological type was adenocarcinoma (41.9%), followed by squamous cell carcinoma (30.0%) and SCLC (15.4%). CONCLUSIONS: The number of diagnosed LC patients in the Northern Serbian region increased over the past decade and is significantly higher in females. There was a strong correlation between smoking habits and LC in both genders. Our results also indicate the importance of introducing and promoting LC screening programs for all risk populations, particularly current and ex-smokers of younger age.

A randomized phase II study of ganetespib, a heat shock protein 90 inhibitor, in combination with docetaxel in second-line therapy of advanced non-small cell lung cancer (GALAXY-1).

BACKGROUND: This trial was designed to evaluate the activity and safety of ganetespib in combination with docetaxel in advanced non-small cell lung cancer (NSCLC) and to identify patient populations most likely to benefit from the combination. PATIENTS AND METHODS: Patients with one prior systemic therapy for advanced disease were eligible. Docetaxel (75 mg/m(2) on day 1) was administered alone or with ganetespib (150 mg/m(2) on days 1 and 15) every 3 weeks. The primary end points were progression-free survival (PFS) in two subgroups of the adenocarcinoma population: patients with elevated lactate dehydrogenase (eLDH) and mutated KRAS (mKRAS). RESULTS: Of 385 patients enrolled, 381 were treated. Early in the trial, increased hemoptysis and lack of efficacy were observed in nonadenocarcinoma patients (n = 71); therefore, only patients with adenocarcinoma histology were subsequently enrolled. Neutropenia was the most common grade ≥3 adverse event: 41% in the combination arm versus 42% in docetaxel alone. There was no improvement in PFS for the combination arm in the eLDH (N = 114, adjusted hazard ratio (HR) = 0.77, P = 0.1134) or mKRAS (N = 89, adjusted HR = 1.11, P = 0.3384) subgroups. In the intent-to-treat adenocarcinoma population, there was a trend in favor of the combination, with PFS (N = 253, adjusted HR = 0.82, P = 0.0784) and overall survival (OS) (adjusted HR = 0.84, P = 0.1139). Exploratory analyses showed significant benefit of the ganetespib combination in the prespecified subgroup of adenocarcinoma patients diagnosed with advanced disease >6 months before study entry (N = 177): PFS (adjusted HR = 0.74, P = 0.0417); OS (adjusted HR = 0.69, P = 0.0191). CONCLUSION: Advanced lung adenocarcinoma patients treated with ganetespib in combination with docetaxel had an acceptable safety profile. While the study's primary end points were not met, significant prolongation of PFS and OS was observed in patients >6 months from diagnosis of advanced disease, a subgroup chosen as the target population for the phase III study.

Neodymium yttrium-aluminium-garnet laser resection significantly improves quality of life in patients with malignant central airway obstruction due to lung cancer.

Neodymium yttrium-aluminium-garnet (Nd : YAG) laser resection is one of the mostly used interventional pulmonology techniques for urgent desobstruction of malignant central airway obstruction (CAO). The major aim of this trial was to evaluate potential influence of Nd : YAG laser resection on overall quality of life (QoL) in patients with central lung cancer. Patients with malignant CAO scheduled for Nd : YAG laser resection were prospectively recruited in the trial. All patients were given European Organization for Research and Treatment, Quality of Life questionnaire (EORTC QLQ-30 v.3) before the procedure and approximately 2 weeks after the treatment. There were 37 male and 10 female patients, average age 54 ± 10 years. Most common tumour type was adenocarcinoma diagnosed in 51% of patients. Majority of patients were diagnosed in stage IIIB (53.2%) and stage IV (25.5%). Most common Eastern Cooperative Oncology Group performance status was 1 (72.3%). Nd : YAG laser resection significantly improved (P<0.0001) QoL and overall health according to EORTC QLQ-30. However, in some of the questions dealing with nausea, vomiting, diarrhoea, constipation, family life, social activities and financial situation, we did not observe statistically significant improvement. Nd : YAG laser resection of malignant CAO significantly improves QoL and overall health in patients with lung cancer.

Clinical prognostic factors and outcome of surgical treatment in patients with early-stage bronchial carcinoid tumors.

PURPOSE: Surgical resection is the treatment of choice for bronchial carcinoids (BC). The primary endpoint of this study was to look at the survival of patients with BC after the surgical treatment and to identify some clinicopathological prognostic factors influencing survival. METHODS: The analysis included 57 patients with early- stage BC submitted to surgical treatment in the period 2000-2008. Major inclusion criteria were: pathologically confirmed BC, ECOG performance status 0-2, and surgical resection of the tumor. RESULTS: No significant difference in survival in relation to gender was registered. N0, N1 and N2 status was registered in 39, 9 and 2 patients, respectively. There were statistically significant differences in survival according to N status (p=0.032). Twenty-two patients had T1N0 stage, 21 T2N0, and 4 T1N1. There was a trend for significant differences in survival according to TN stage (p=0.063). Also, analysis revealed significant differences in survival depending on tumor size (p=0.000), as well as on the type of the tumor (typical vs. atypical) (p=0.010). CONCLUSION: Nodal status and TN stage affect patients' survival. Tumor size and typical/atypical tumor are also significant prognostic factors for survival of surgically treated patients.

Aprepitant--where do we stand in the control of chemotherapy-induced nausea and vomiting?

Despite progress in the area of supportive care in oncology in the last two decades, nausea and vomiting continue to be significant side effects of cancer therapy. These symptoms can escalate over time and can result in patients' refusal to continue with chemotherapy. Introduction of serotonin (5-HT3) receptor antagonists was a major therapeutic advance in the treatment of chemotherapy-induced nausea and vomiting with enhanced efficacy when corticosteroids were added. However, these agents have limited protection in the acute phase of chemotherapy-induced nausea and vomiting with little or no effect over the delayed phase. The aim of this review was to introduce a new class of antiemetics, a selective high-affinity antagonist at human substance P neurokinin 1 (NK(1)) receptors-aprepitant. Its pharmacological characteristics as well as its efficacy are reviewed. Aprepitant appears to be well tolerated but, due to its inhibitory effect on cytochrome P450 isoenzyme 3A4, it can lead to significant drug interactions, resulting in need for dose modification of concomitant therapy. The addition of aprepitant to 5-HT(3) receptor antagonists and corticosteroids was found to be superior to the combination of 5-HT(3) receptor antagonists and corticosteroids alone in patients treated with highly and moderately emetogenic chemotherapy. Clinical trials with aprepitant and other antiemetic agents are warranted to determine a regimen that will ensure complete protection from both acute and delayed chemotherapy-induced nausea and vomiting, thus contributing to improved supportive care and patients' quality of life (QoL).

The effect of Nd:YAG laser resection on symptom control, time to progression and survival in lung cancer patients.

PURPOSE: The aim of this study was to determine the effect of Nd:YAG laser resection of centrally located tumors on the control of various symptoms and signs, time to progression and survival in lung cancer patients. PATIENTS AND METHODS: We evaluated the effects of Nd: YAG laser resection in combination with high-dose rate (HDR) brachytherapy and external beam radiotherapy (EBRT) vs. combination of HDR brachytherapy and EBRT alone on lung cancer symptoms and signs, ECOG performance status, time to progression and overall survival in lung cancer patients. Patients in group I (n=81) were treated with combination of HDR brachytherapy and EBRT, while patients in group II (n=97) were treated with Nd:YAG laser in combination with HDR brachytherapy and EBRT. Patients were evaluated before and after treatment, and were followed-up regularly every 3 months until the end of life. After RT +/- laser treatment all patients received standard chemotherapy (cisplatin plus etoposide) during the course of disease. RESULTS: After treatment in both groups significant improvement in all investigated parameters was seen. Improvement in dyspnoea, thoracic pain, body weight loss and ECOG performance status was significantly better in group II (p <0.05), as were time to progression and overall survival (p <0.05). CONCLUSION: Laser resection improves symptom control in lung cancer patients with central airway obstruction (CAO). Longer time to progression and survival of lung cancer patients could be the result of imminent airway desobstruction accomplished with Nd:YAG laser.

Clinical presentation, treatment options and outcome in patients with bronchioloalveolar carcinoma.

PURPOSE: To determine the characteristics of bronchioloalveolar carcinoma (BAC) as a special clinical and pathological entity and to evaluate the effects of treatment options on survival of BAC patients. PATIENTS AND METHODS: The study was partially retrospective and partially prospective, non randomized. We evaluated the clinical presentation, smoking habits, radiographic findings, treatment and survival of 21 patients with BAC treated at our Institute from 2000-2004. RESULTS: Registered were 16 (76.2%) male and 5 (23.8%) female patients, most of them in the 6th and 7th decade of life. Among younger patients females prevailed. Most common symptoms were dyspnoea 15 (71.4%), cough 14 (66.6%) and bronchial hypersecretion 9 (42.8%). There were 5 (23.8%) smokers, 6 (28.6%) ex-smokers and 10 (47.6%) nonsmokers. Main radiographic findings were lung consolidation (9; 42.8%), diffuse interstitial infiltrates (6; 28.6%), solitary (4; 19.0%) and multiple pulmonary lesions (2; 9.5%). Surgery was performed in 8 (38.0%) patients and 5 of them received adjuvant radio- and chemotherapy, while the remaining received chemotherapy alone (9; 42.8%) and symptomatic treatment (4; 19.0%). The median survival was 25 months and 1-year survival 70%, regardless of stage. In the group of patients treated surgically 1- and 2-year survival rate was 100% and the median survival 33 months. In non-operated patients the median survival was 18 months and 1- and 2-year survival 55% and 25%, respectively. CONCLUSION: BAC is a special clinical and pathological form of adenocarcinoma of the lung. Surgical treatment is the best option for selected BAC patients. Survival is associated with the treatment modality. Larger scale studies are necessary to confirm these findings.

The influence of dexamethasone in the decrease of chemotherapy-induced nausea and vomiting.

PURPOSE: The aim of this study was to determine the influence of dexamethasone in the decrease of cisplatin and etoposide-induced nausea and vomiting in patients treated for lung cancer during and after 2 chemotherapy cycles. PATIENTS AND METHODS: The analysis included 60 patients with histologically proven lung cancer, who were divided in two groups. Group A consisted of 30 patients who received cisplatin and etoposide with standard antiemetic drugs: ondansetron [serotonin receptor antagonist (5-HT(3) antagonist)] and metoclopramide (dopamine receptor antagonist). Group B consisted of 30 patients who received the same chemotherapy regimen with the previous antiemetic therapy plus dexamethasone 8 mg intravenously (i.v.) per day during the 3 days of chemotherapy. During and after the 3-day therapy, patients filled in a questionnaire issuing adverse effects of chemotherapy concerning many symptoms including nausea and vomiting. The results were statistically processed. RESULTS: There was a significant decrease in the frequency and toxicity of nausea, acute and delayed vomiting in the group of patients who received antiemetic treatment with ondansetron, metoclopramide plus dexamethasone. CONCLUSION: Dexamethasone administered with 5-HT(3) antagonists and dopamine receptor antagonists significantly decreases the chemotherapy-induced nausea and vomiting.

Interventional pulmonology techniques for immediate desobstruction of malignant central airway obstruction.

In recent years interventional pulmonology techniques have found their place in the palliative treatment of lung cancer invading central airways (trachea and principal bronchi). The curative effect of interventional techniques is reported in a number of studies with very different success ratios, but with excellent potential and perspective. Increase in number and variety of these techniques led to the development of internationally accepted guidelines for their use. The choice of a specific interventional technique in the treatment of lung cancer patients with central airway obstruction (CAO) depends on several factors: patient's general condition and comorbidities, type and characteristics of airway stenosis, availability of techniques and trained personnel. The aim of this review was to introduce interventional pulmonology procedures aimed at urgent desobstruction of central airways obstruction to medical oncologists who are dealing with the problem of malignant CAO. We tried to emphasize indications, contraindications, technique procedure and possible complications in the treatment of malignant CAO. At the Institute for Pulmonary Diseases of Vojvodina Nd: YAG laser resection, electrocautery, argon plasma coagulation and metallic and silicone stent insertions for immediate treatment of malignant CAO are practised.

Combination of interventional pulmonology techniques (Nd:YAG laser resection and brachytherapy) with external beam radiotherapy in the treatment of lung cancer patients with Karnofsky Index < or =50.

PURPOSE: To compare Nd: YAG laser resection with Nd: YAG laser plus brachytherapy and external beam radiotherapy (EBRT) in the palliation of malignant central airway obstruction symptoms due to lung cancer. PATIENTS AND METHODS: In this prospective non-randomized study we evaluated the effects of Nd:YAG laser photoresection alone vs. Nd:YAG laser resection in combination with brachytherapy and EBRT on cough, dyspnoea, thoracic pain, haemoptysis, body weight loss, atelectasis, postobstructive pneumonia, endoscopic findings, disease-free period and survival rate in lung cancer patients. Only patients with Karnofsky index (KI) < or =50 were included. Sixty-four patients were divided into 2 groups: group I patients ( = 20) were treated only with Nd: YAG laser, and group II patients (n = 44) were treated with Nd: YAG laser followed by brachytherapy and EBRT. RESULTS: Group I patients showed statistically significant improvement in all investigated parameters but cough. Group II patients achieved significant improvement in all investigated parameters. Comparative statistical analysis between the 2 groups revealed statistically significant improvement in group II with regard to dyspnoea, haemoptysis, KI and atelectasis. No significant improvement in group II was seen when other investigated parameters were considered. Disease-free period and survival rate were significantly longer in group II (p< or =0.0005). CONCLUSION: The combination of interventional pulmonology procedures with standard modalities is the best option for the treatment of selected lung cancer patients.

Bronchodilatation test response predictors in lung function assessment of patients with resectable lung cancer and concomitant chronic obstructive pulmonary disease.

PURPOSE: The goal of this pilot study was to determine factors influencing the bronchodilatation test (BDT) response during preoperative lung function assessment in patients with resectable non-small cell lung cancer (NSCLC) and concomitant chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: The analysis included 34 patients who met the following entry criteria: preoperative lung function assessment including a BDT, presence of operable, histologically confirmed stage IA-IIIA NSCLC established by computerized tomography (CT) and endoscopical findings, no more than one cardiovascular risk factor present, no interstitial pulmonary diseases (restriction exclusively due to the tumor), and patient's age up to 70 years. The study was partially retrospective and partially prospective. BDT was performed by forced expiratory volume in the first second (FEV1) measurement prior to and 30 min after two Berodual(R) inhalations (0.005 mg of fenoterol + 0.002 mg of ipratropium bromide per inhalation). RESULTS: Possible predictors of BDT response may include history of COPD longer than 15 years, N2 lymph nodes involvement, total lung restriction, and presence of a visible tumor in the main and intermediate bronchus. CONCLUSION: These possible predictors remain hypothetical as the study cohort is rather small, so a large scale research should follow to provide reliable data necessary to make definite conclusions.