Unresectable stage III non-small cell lung cancer: Insights from a Portuguese expert panel.

INTRODUCTION: The management of unresectable stage III non-small cell lung cancer (NSCLC) is clinically challenging and there is no current consensus on optimal strategies. Herein, a panel of Portuguese experts aims to present practical recommendations for the global management of unresectable stage III NSCLC patients. METHODS: A group of Portuguese lung cancer experts debated aspects related to the diagnosis, staging and treatment of unresectable stage III NSCLC in light of current evidence. Recent breakthroughs in immunotherapy as part of a standard therapeutic approach were also discussed. This review exposes the major conclusions obtained. RESULTS: Practical recommendations for the management of unresectable stage III NSCLC were proposed, aiming to improve the pathways of diagnosis and treatment in the Portuguese healthcare system. Clinical heterogeneity of patients with stage III NSCLC hinders the development of single standardised algorithm where all fit. CONCLUSIONS: A timely diagnosis and a proper staging contribute to the best management of each patient, optimizing treatment tolerance and effectiveness. The expert panel considered chemoradiotherapy as the preferable approach when surgery is not possible. Management of adverse events and immunotherapy as a consolidation therapy are also essential steps for a successful strategy.

Real-world data from the Portuguese Nivolumab Expanded Access Program (EAP) in previously treated Non Small Cell Lung Cancer (NSCLC).

OBJECTIVE: The main aim of the study was to evaluate the efficacy and safety profile of Nivolumab, an immune-checkpoint-inhibitor antibody, in advanced, previously treated, Non-Small Cell Lung Cancer (NSCLC) patients, in a real world setting. METHODS: We performed a retrospective, multicentre data analysis of patients who were included in the Portuguese Nivolumab Expanded Access Program (EAP). Eligibility criteria included histologically or citologically confirmed NSCLC, stage IIIB and IV, evaluable disease, sufficient organ function and at least one prior line of chemotherapy. The endpoints included Overall Response Rate (ORR), Disease Control Rate (DCR), Progression Free Survival (PFS) and Overall Survival (OS). Safety analysis was performed with the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, and immune-related Adverse Events (irAEs) were treated according to protocol treatment guidelines. Tumour response was assessed using the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. Data was analysed using SPSS, version 21.0 (IBM Statistics). RESULTS: From June 2015 to December 2016, a total of 229 patients with advanced NSCLC were enrolled at 30 Portuguese centres. Clinical data were collected up to the end of July 2018. The baseline median age was 64 years (range 37-83) and the majority of patients were males (70.3%) and former/current smokers (69.4%). Patients with non-squamous histology predominated (88.1%), and 67.6% of the patients had received 2 or more prior lines of chemotherapy. Out of 229 patients, data was available for 219 patients (3 patients did not start treatment, while data was unavailable in 7 patients); of the 219 patients, 15.5% were not evaluated for radiological tumour assessment, 1.4% had complete response (CR), 21% partial response (PR), 31% stable disease (SD) and 31.1% progressive disease (PD). Thus, the ORR was 22.4% and DCR was 53.4% in this population. At the time of survival analysis the median PFS was 4.91 months (95% CI, 3.89-6.11) and median OS was 13.21 months (95% CI, 9.89-16.53). The safety profile was in line with clinical trial data. CONCLUSIONS: Efficacy and safety results observed in this retrospective analysis were consistent with observations reported in clinical trials and from other centres.

Diffuse vascular hamartoma with malignant behavior.

Pulmonary hamartomas are benign lesions, usually asymptomatic and incidentally discovered on a routine chest radiograph; occasionally, however, this benign lesion may cause life threatening symptoms due to it's location and diffuse vascular involvement. We report the case of a 27 year-old male, non-smoker, who presented with dyspnea, cough, hemoptysis and weight loss. He was found to have a mass in the right hilar region which also involved the right main bronchus, pulmonary artery and esophagus. Surgical biopsy of the lesion led to the diagnosis of diffuse vascular hamartoma. Although it was a benign lesion, due to the size and location, surgical removal was not possible and patient died 10 years after being diagnosed with the condition.

Lung cancer in Northern Portugal: A hospital-based study.

INTRODUCTION: Lung cancer is the deadliest cancer worldwide. In Portugal, the disease remains the main cause of cancer death in males. AIM: This study aims to evaluate the demographic and clinical characteristics of lung cancer patients diagnosed and treated in northern Portugal hospitals from 2000 to 2010. PATIENTS AND METHODS: Twelve hospitals in the north of Portugal contributed to this study. The demographic and clinic characteristics of the patients registered in each hospital from 2000 to 2010 and the patterns of their occurrence were analyzed. RESULTS: During an 11-year period (2000-2010), 9767 lung cancer patients were registered in the participating hospitals. Comparing the number of the patients registered in the year 2000 to those registered during 2010, there was a significant increase in lung cancer cases. Females represent only 20% of the total registered lung cancer cases; however, during the study period, the number of female patients increased by 30%. A significant number of the patients, 3117 (48.6%), had poor performance status at presentation. The adenocarcinoma histology became more preponderant over the study period. Most of the patients were diagnosed as stages IIIB or IV: 7206 of 9267 (77.8%). Chemotherapy was the treatment of choice for 3529 (40.4%) patients, whereas surgical treatment was achieved in 1301 (14.9%) cases. CONCLUSION: A significant number of lung cancer patients have been diagnosed and treated in hospitals in northern Portugal, and the incidence of the disease among females has been increasing. The overwhelming majority of the tumors were diagnosed in advanced stage; nevertheless, surgical treatment was possible in 14.9% of the patients.

Well-differentiated papillary mesothelioma: clustering in a Portuguese family with a germline BAP1 mutation.

BACKGROUND: Well-differentiated papillary mesothelioma (WDPM) is a rare variant of epithelioid mesothelioma and is considered to be associated with good prognosis due to its clinically indolent behavior and long survival. Most reported cases involve the peritoneum of women at reproductive age with no history of exposure to asbestos, with pleural involvement being less common. The optimal management, including the role of chemotherapy in the treatment of WDPM, remains unsettled. PATIENTS AND METHODS: The authors describe two cases of WDPM in women of the same family (siblings); the elder with WDPM of the pleura and peritoneum with a 12-year survival period and the younger with a WDPM of the peritoneum diagnosed in 2011 and uveal melanoma diagnosed in 2012. Neither patient had any known exposure to asbestos fibers or any other mineral carcinogens. RESULTS: After the concurrent diagnosis of WDPM and uveal melanoma, genetic diagnosis was carried out taking into consideration that these two malignancies were recently associated with hereditary BAP1 gene mutations and it was positive for both the patients. CONCLUSIONS: To our knowledge, this is the first description of WDPM in two siblings who also presented with a germline BAP1 mutation. This article provides evidence of the wide clinical spectrum of cancer susceptibility associated with a BAP1 germline mutation.

Dermatomyositis as the first manifestation of a lung tumor.

Dermatomyositis (DM) is a rare disease characterised by proximal muscle weakness and a typical cutaneous rash. The muscle biopsy shows inflammatory lesions consistent with myositis, being related to an increased risk of cancer, often considered as a paraneoplastic syndrome. The authors present a case of a 63-year-old man, with progressive proximal muscle weakness and cutaneous rash, appearing in two months. The muscle and skin biopsies were consistent with DM. Chest tomography showed a nodular image in the lingular region and bronchy biopsy confirmed the diagnosis of small cell lung carcinoma (SCLC). This clinical case intends to enhance the importance of a thorough diagnostic study in patients with DM, as it is often a paraneoplastic syndrome.

Epidermal growth factor receptor mutation study for 5 years, in a population of patients with non-small cell lung cancer.

INTRODUCTION: In 2006, the Vila Nova de Gaia/Espinho Hospital Centre Pulmonary Oncology Unit started performing EGFR (Epidermal Growth Factor Receptor) mutation sequencing in selected patients with NSCLC and systematically in all patients since 2010, regardless of histology, smoking habits, age or sex. The aim of this study was to characterize the group of patients that carried out the sequencing between 2006-2010, to determine EGFR mutation frequency, to evaluate the overall survival and the survival after the use of tyrosine kinase inhibitors (TKI), in patients who performed this therapy in second and third line, knowing the EGFR mutation status. METHODS: Descriptive statistical analysis of patients who did EGFR sequencing in 2006-2010 and of overall survival in patients treated with TKI as 2nd and 3rd line therapy. Record of the material available for analysis and average delay of exam results, according to the material submitted. RESULTS: The sequencing was performed in 374 patients, 71,1% males, 67,1% non/ex-smokers, 32,9% smokers, 57,8% adenocarcinoma and 23,5% squamous cell carcinoma (SCC). The mutation was detected in 49 patients (13,1%). In all studied patients, the mutation rate was 9% in males and 23% in females. Median overall survival after erlotinib use of was 14 months for patients with positive EGFR mutation versus 6 months in not mutated patients (p = 0.003). CONCLUSION: Our group had an overall mutation rate of 13.1% with female, non-smokers, adenocarcinoma histology predominance. In selected patients (2006/2009), the mutation rate was 16%, in not selected patients (2010) the mutation rate was 10.4%. This study has permitted a better understanding of the EGFR mutation rate in the Portuguese population as welll as an evaluation of the patients survival after the use of of tyrosine kinase inhibitors, in second and third line therapy with previous knowledge of the EGFR mutational status. Statistical significant differences in survival were found in the two patient groups (EGFR mutated and non mutated). The EGFR mutation research should be performed in all patients with NSCLC, giving the possibility to a considerable number of patients to perform a first line treatment with TKI (EGFR mutated patients) and the advantage of performing other chemotherapy schemes, when progression occurs.

[Undernutrition and quality of life in non small cell lung cancer patients]. / Desnutrição e Qualidade de Vida em Doentes com Cancro do Pulmão Não Pequenas Células.

Cancer is related to a deterioration of nutritional status and quality of life (QoL), but the extent of these conditions in patients with Non Small Cell Lung Cancer (NSCLC) has not been studied. The aim of the present study was to assess the association between QoL and undernutrition in NSCLC patients. Nutritional status was evaluated with Patient Generated - Subjective Global Assessment and QoL using the European Organization for Research and Treatment of Cancer Quality of Life - C30 and also with the specific module for lung cancer patients. A consecutive sample of fifty six patients diagnosed with NSCLC was evaluated. A high proportion of patients is undernourished (35.7%), 1.8% in early stages vs 33.9% in advanced stages of disease. Undernutrition is related to measured dimensions of QoL: lack of appetite (rho=0.70), fatigue (rho=0.54), nausea and vomiting (rho=0.52) and constipation (rho=0.56). Undernourished patients have worse global health status, physical, emotional, social and role functioning. Patients with NSCLC have high frequency of undernutrition in advanced stages of disease. Undernourished patients present more symptoms, a worse global health status/QoL, physical, role, emotional and social functioning than patients without undernutrition. Undernutrition is associated with worse QoL, specifically in the parameters: appetite loss, nausea and vomiting, constipation and fatigue.

Portuguese Journal of Pulmonology: year-in-review 2009.

The Portuguese Journal of Pulmonology is progressively achieving an important status in Portuguese medical literature. The present editors thought it would be an enriching task to revise the main topics published during 2009. The invited members of the Editorial Board covered and commented the most relevant articles and gave us an important picture of the quality of the science it was published in Portuguese Pulmonology.

An economic analysis of erlotinib, docetaxel, pemetrexed and best supportive care as second or third line treatment of non-small cell lung cancer.

AIM: Evaluate costs and benefits of erlotinib as 2nd or 3rd line treatment of advanced or metastatic nonsmall cell lung cancer (NSCLC) versus docetaxel, pemetrexed and best supportive care. MATERIALS AND METHODS: Cost-minimisation and cost-utility analysis were performed. Time horizon of two years. Portuguese National Health System (NHS) perspective was applied. Survival and time to progression were obtained from three clinical trials. Base-case analysis: 2nd or 3rd line patients with advanced or metastatic NSCLC. Quality Adjusted Life Years (QALYs) were obtained from a UK study. Resource consumption was estimated by a Portuguese panel of experts. Costs were calculated according to official Portuguese databases (updated to 2008). Only direct health costs were applied. Annual discount rate: 5%. Sensitivity analysis included different subpopulations, a three year time horizon and a probabilistic analysis. RESULTS: The cost per patient was lower with erlotinib (26,478 euro) than docetaxel (29,262 euro) or pemetrexed (32,762 euro) and higher than best supportive care (16,112 euro). QALYs per patient were higher with erlotinib (0.250) than docetaxel (0.225), pemetrexed (0.241) or best supportive care (0.186). Erlotinib was dominant in the cost-utility analysis, with a lower cost and a higher efficacy than docetaxel and pemetrexed. The sensitivity analysis confirmed the robustness of the base-case analysis results. CONCLUSIONS: The use of erlotinib instead of docetaxel or pemetrexed could contribute to annual savings for the NHS (substitution rates: 5%-65%) ranging from 135,046 euro-1,755,602 euro (docetaxel replacement) and 291,801 euro-3,793,409 euro (pemetrexed replacement), with a gain in terms of QALYs.

Characterization of a Staphylococcus aureus strain showing high levels of biofilm formation isolated from a vascular graft: case report.

A methicillin-susceptible Staphylococcus aureus strain, SA-DZ1, was isolated from an infected bypass crossover graft. Its general microbiological features were reminiscent of those previously described for the wound Wiley strain. Removal of the prosthetic device was necessary to resolve the infection. SA-DZ1 grown under different conditions showed a very strong and distinctive biofilm-producing phenotype, which was also visualized by confocal laser scanning microscopy. The biofilm extracellular matrix was essentially polysaccharidic, as determined by differential growth and physicochemical tests. By Multi Locus Sequence Typing (MLST), SA-DZ1 was classified as st94, a single locus variant of st8. Several other genetic traits assayed by PCR, such as agr-type and the presence of gene encoding proteins involved in adhesion and virulence (e.g. ica operon), confirmed the identifying features of this clinical isolate.

Pemetrexed in second line treatment of non-small cell lung cancer - The portuguese experience. / Pemetrexed na segunda linha de tratamento do carcinoma do pulmão de não pequenas células - A experiência portuguesa.

Until 2004, docetaxel in monotherapy was the standard for second-line treatment of non-small cell lung cancer (NSCLC). Pemetrexed (P) has shown similar activity in this setting with a better adverse event profile. In Portugal, it was introduced in October of 2004. We have carried out a retrospective analysis of patients (pts) who received P for second-line NSCLC in Portugal from October 2004 to December 2006. Data were collected from the records of pts with locally advanced or metastatic NSCLC and failed first-line chemotherapy enrolled in centers participating in the Portuguese Lung Cancer Study Group (GECP). Objective response (OR; complete [CR] or partial [PR] response) was evaluated using RECIST and safety was assessed using serious or non-serious adverse events (SAEs/AEs). By December 2006, 19 GECP centers had enrolled 244 pts who had received P for ≥1cycle, and were considered evaluable for both objective response and safety. Demography: male/female, 175/69; median age, 57.0years (range 20-81); smoking status, y/ex/n, 116/57/71; adenocarcinoma / squamous-cell carcinoma/other histology, 141/72/31; mean time to progression (TTP) 8.07months. Disease control in 209 evaluable pts was observed in 116 (55.5%): 2 CR, 45 PR and 69 SD; mean TTP 4.70months. The majority of AEs were grade 3 anemia (15 pts) and neutropenia (18 pts). The mean overall survival was 17.27months. Our retrospective analysis has observed a similar disease control rate with P in 2nd line (55.5%), and TTP (4.7months) in our current unselected population to that published in the literature. P is an option for second-line NSCLC with a good tolerability. Rev Port Pneumol 2008; XIV (Sup.2): S9-S20.

Positron emission tomography: indications in lung cancer - prospective experience of a department.

Positron emission tomography (PET) is a new technique in nuclear medicine. It uses biological radiotracers such as (18)F-fluoro-2-deoxyglucose (FDG) which permit the detection of suspected lesions with metabolic alterations that take up the glucose isotope too avidly, as is the case with neoplastic cells. PET has become an innovatory and important imaging tool for evaluating patients with lung cancer. The present recommended uses of PET include lung cancer diagnosis and the intrathoracic and extrathoracic staging in N-SCLC.

Retroperitoneoscopic lumbar sympathectomy for nonreconstructable arterial occlusive disease.

AIM: The aim of this study was to present our experience with video-assisted lumbar sympathectomy for non-reconstructive arterial occlusive disease in a series of 23 consecutive patients whose predominant symptoms were unilateral rest pain, limited skin ulcerations or gangrene of the toes. METHODS: All the procedures were performed with retroperitoneal approach, dorsal position of the patient and simple digital dissection of the retroperitoneal space. RESULTS: The operations were successfully performed in all patients except for 2, who immediately underwent open conversion. A urinoma caused by ureteral lesion was the only severe complication in this series. The mean operative time of the procedure was 55 min and the hospital stay was 2 or 3 days. No parenteral analgesics were administered postoperatively. At 1 month from operation, 20 patients out of 23 had significant relief of rest pain and improvement of ischemic lesions. After a median follow-up of 36 months, 2 patients had died, 4 underwent some type of distal amputation, 1 had recurrent rest pain and the other 16 reported persistent improvement of pain or dystrophic changes. CONCLUSIONS: Retro-peritoneoscopic technique appears the modern and less invasive version of the lumbar surgical sympathectomy.

[Lung cancer and women]. / A mulher e o cancro do pulmão.

The epidemiology of lung cancer has changed in the last years in several countries all over the world. In the 19th century, the lung cancer was rare but it incidence increase drastically during the 20th century, and the tendency is to continue in the 20th century. Actually the lung cancer's incidence and mortality are higher in the developed countries, especially in Europe and Unites States of America, with a increasing in the women incidence. These geographic differences and gender differences are related with smoking habits. Women begin to smoke earlier and have more difficulty to stop, because of problems related with obesity; they have more sensibility to the carcinogens and the risk of lung cancer is 1.5 times higher than the men with the same habits. Adenocarcinoma is the more frequent histological type in young people, in the total of the women and in non-smokers. Many factors since tobacco, home and professional pollution, nutritional, associated diseases even genetic and hormonal factors have been investigated to define its influence in development in women lung cancer. It specificity in women with lung cancer is the common problem for the medical people to treat this disease (pathology).The literature about this problem is not clear, and is necessary to advance with many studies in this area with the objective to clarify this important question.

A prospective study of gemcitabine and carboplatin as first-line therapy in advanced non-small cell lung cancer: toxicity of a three- versus a four-week schedule.

We evaluated the toxicity and activity of gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) and carboplatin on a 3-week (trial A) versus a 4-week (trial B) schedule in patients with advanced/metastatic non-small cell lung cancer. Chemotherapy-naive patients in trial A received gemcitabine 1,000 mg/m(2) on days 1 and 8 plus carboplatin area under the curve of 5 on day 1, every 3 weeks. In trial B, patients received gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 and carboplatin area under the curve of 6 on day 1, every 4 weeks. Thirty patients were enrolled in trial A and 28 in trial B. Patients received a total of 142 cycles in trial A and 134 in trial B. Despite more frequent treatment delays (82 cycles in trial B and 20 cycles in trial A), and dose reductions/omissions (mainly on day 15), gemcitabine mean dose intensities of both schedules were similar. The principal dose-limiting toxicity was grade 3/4 thrombocytopenia. Objective response rates were 40% in trial A and 68% in trial B (no complete response). Gemcitabine and carboplatin administered on days 1 and 8 every 3 weeks is associated with lower myelotoxicity than that of a 4-week schedule, although both schedules were active against non-small cell lung cancer. Semin Oncol 28 (suppl 10):10-14.