Clinical feasibility of NGS liquid biopsy analysis in NSCLC patients.

BACKGROUND: Analysis of circulating tumor nucleic acids in plasma of Non-Small Cell Lung Cancer (NSCLC) patients is the most widespread and documented form of "liquid biopsy" and provides real-time information on the molecular profile of the tumor without an invasive tissue biopsy. METHODS: Liquid biopsy analysis was requested by the referral physician in 121 NSCLC patients at diagnosis and was performed using a sensitive Next Generation Sequencing assay. Additionally, a comparative analysis of NSCLC patients at relapse following EGFR Tyrosine Kinase Inhibitor (TKIs) treatment was performed in 50 patients by both the cobas and NGS platforms. RESULTS: At least one mutation was identified in almost 49% of the cases by the NGS approach in NSCLC patients analyzed at diagnosis. In 36 cases with paired tissue available a high concordance of 86.11% was observed for clinically relevant mutations, with a Positive Predictive Value (PPV) of 88.89%. Furthermore, a concordance rate of 82% between cobas and the NGS approach for the EGFR sensitizing mutations (in exons 18, 19, 21) was observed in patients with acquired resistance to EGFR TKIs, while this concordance was 94% for the p.T790M mutation, with NGS being able to detect this mutation in three 3 additional patients. CONCLUSIONS: This study indicates the feasibility of circulating tumor nucleic acids (ctNA) analysis as a tumor biopsy surrogate in clinical practice for NSCLC personalized treatment decision making. The use of new sensitive NGS techniques can reliably detect tumor-derived mutations in liquid biopsy and provide clinically relevant information both before and after targeted treatment in patients with NSCLC. Thus, it could aid physicians in treatment decision making in clinical practice.

Pulmonary adenocarcinoma presenting with penile metastasis: a case report.

INTRODUCTION: Penile metastases are an extremely rare occurrence, and most primary malignancies are located in the urinary bladder, prostate, rectum, and rectosigmoid. Although very few cases of penile metastases have been reported, those of lung cancer as the primary tumor are very rare. Among the latter, squamous cell carcinomas constitute the majority, whereas adenocarcinomas are almost exceptions. To the best of our knowledge, only two cases have been reported. CASE PRESENTATION: We report the case of a 59-year-old Greek man who presented with persistent cough and chest pain that had started one month prior to a medical appointment. A physical examination, complete laboratory work-up, computed tomography scanning (of the chest, brain, and abdomen), pelvic magnetic resonance imaging, penile ultrasonography, bone scanning, and histological analyses were conducted. Afterward, a lung adenocarcinoma metastatic to the bones, brain, adrenals, lymph nodes, and penis was diagnosed. The primary lesion was a mass of 4cm in diameter in the apical segment of the lower lobe of the right lung. The patient was treated with bone and brain radiotherapy and various cycles of first- and second-line chemotherapy, and partial response was achieved five months after the initial appointment. CONCLUSIONS: Although these metastatic sites are well known to occur from a primary pulmonary malignancy, penile metastasis is extremely rare. Its identification requires prompt awareness by the physician despite the dismal prognosis. Furthermore, since the penis usually is omitted from the physical examination and lung cancer is the leading cause of cancer-related deaths, more penile metastases may be detected in the future, making early detection and appropriate management of great importance.

Pulmonary blastoma with submandibular, scrotum and adrenal metastases: case report.

A 62-year-old patient diagnosed with pulmonary blastoma with submandibular, scrotum and adrenal metastases was admitted to Sotiria General Hospital in Athens. No other such case has been published to date. The patient started receiving chemotherapy, but the scrotum metastasis grew rapidly and erupted. This led to sepsis despite surgical excision of infected and necrotic tissues and intravenous antibiotics. Treatment strategy in pulmonary blastoma should be defined by a multidisciplinary team, and surgical treatment should be considered as quickly as possible when such a tumor is suspected.

Carboplatin plus pemetrexed as first-line treatment of patients with malignant pleural mesothelioma: a phase II study.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is a rapidly progressive tumor that is increasing in frequency worldwide. Treatment options are limited, and response to chemotherapy is poor. The aim of this phase II study was to evaluate the activity of the carboplatin/pemetrexed combination as first-line chemotherapy in patients with unresectable MPM. PATIENTS AND METHODS: Chemotherapy-naive patients with histologically confirmed MPM and an Eastern Cooperative Oncology Group performance status of 0-2 were enrolled. Treatment consisted of pemetrexed 500 mg/m2 and carboplatin area under the concentration-time curve of 5 mg/mL/min, both administered on day 1 of a 21-day cycle. The treatment continued until 6 cycles were completed or until unacceptable toxicity or disease progression were observed. RESULTS: A total of 62 patients were enrolled. Of these patients, 18 (29%) had a confirmed partial response, whereas the disease remained stable in 34 patients (54.9%) and progressed in 10 patients (16.1%). The median overall survival (OS) was estimated at 14 months (95% CI, 11.8-16.2 months), and the median time to progression was 7 months (95% CI, 5.8-8.2 months). The difference in median OS between the epithelial histologic subtype (16 months) and the sarcomatoid subtype (11 months) was statistically significant. CONCLUSION: This study confirmed the activity of the carboplatin/ pemetrexed combination in the first-line treatment of patients with MPM. It is a viable option, especially in cases in which side effects are generally anticipated.

Docetaxel plus gemcitabine as first-line treatment in malignant pleural mesothelioma: a single institution phase II study.

BACKGROUND: The cisplatin-pemetrexed and cisplatin-gemcitabine combinations are considered the standard treatment for malignant pleural mesothelioma. The purpose of this study was to examine the efficacy of gemcitabine plus docetaxel in the first-line setting, as this combination has not been investigated in mesothelioma before. PATIENTS AND METHODS: Twenty-five consecutive patients with malignant pleural mesothelioma were enrolled. They received 80 mg/m(2) of docetaxel and 1,000 mg/m(2) of gemcitabine on days 1 and 14 of a 28-day cycle. The treatment was scheduled for a maximum of 6 cycles or until disease progression or unacceptable toxicity. RESULTS: A total of 7 out of our 25 patients (28%) responded to treatment. In 14 patients (56%), the disease remained stable, while in 4 (16%) it progressed. The median time to progression was 7 months (range: 5.4-8.6 months) and the median overall survival was 15 months (range: 12.4-17.5 months). CONCLUSION: The administration of gemcitabine and doctaxel appears to be promising first-line therapy for patients with mesothelioma, as it is well tolerated and appears to improve survival.

Skin cancer in the elderly.

With the significant increase in the average life-span in the industrial world, skin cancer has become a great health concern. There are various epidemiological, biological and molecular data suggesting that skin cancer is predominantly a disease of the elderly, since approximately 53% of skin cancer-related deaths occur in persons more than 65 years old. With regard to the management of elderly patients with skin cancer, this should be individualized depending upon the clinical performance status, and age alone should not constitute an obstruction for the administration of the optimal treatment. Since elderly patients with melanoma have a worse prognosis, emphasis should be given to primary and secondary prevention. Physicians treating elderly patients should be trained in an individualized approach to these patients and encouraged to participate in programs for the early detection of suspicious skin lesions.

Safety and efficacy of the new bisphosphonate ibandronate in the management of bone metastasis following rapid infusion.

BACKGROUND: We evaluated the safety and efficacy of the new BP ibandronate, given as a rapid infusion. PATIENTS AND METHODS: We administered 4 mg of ibandronate as an intravenous infusion over 30 minutes. Thirty patients (16 breast cancers, 4 prostate cancers, 10 multiple myelomas) with bone metastases received 4 mg of ibandronate injected intravenously over 30 minutes in normal saline 0.9%, 250cc every 3 or 4 weeks. The patients were followed-up over 2 hours after infusion. A total of 198 infusions were administered over a period of 24 months and the patients were followed-up for long-term ibandronate-related side-effects, as well as for any potential clinical benefit. RESULTS: Following the first administration of ibantronate, serum levels of calcium, phosphate and alkaline phosphatase were significantly decreased and the difference was statistically significant (p < 0.001) for all three parameters examined. The reduced time of infusion (30 minutes vs 2 hours) did not correlate with any side-effects during or post-administration. Serum levels of creatinine and urea nitrogen did not increase significantly, while changes in temperature and blood pressure were not detected in the patients examined. With regard to efficacy, all the patients, after repeated administrations, reduced the doses of analgesics needed; 26 out of 30 patients had stable disease in the bones while 1 out of 30 patients had significant improvement of bone lesions in consecutive bone scans. CONCLUSION: Infusional administration of ibandronate is efficient in the management of hypercalcaemia of malignancy and it results in a reduced need for analgesics. The rapid infusion over 30 minutes is safe and could be given in the setting of a day care unit.