Despite vigorous efforts at curbing tobacco consumption and aggressive combined-modality treatment programs, both the incidence of and the mortality from lung cancer have remained virtually unchanged in the last 10 years. More effective innovative therapies are clearly needed. The direct transfer into tumor cells of tumor suppressor genes or toxic gene products that specifically promote tumor cell death and spare nonmalignant cells is a potentially novel anticancer treatment approach that should be investigated. Purpose: On the basis of compelling preclinical data, we initiated a phase I study involving six patients with inoperable lung cancer and an endobronchial lesion accessible by bronchoscopy. Our purpose was to evaluate the feasibility, tolerance, and clinical, biologic, and immunologic effects of the intratumoral administration of a recombinant, replication-deficient adenovirus (rAd.RSVβ-gal), using the Rous sarcoma virus promoter to drive transcription of the Escherichia coli lacZ marker gene that encodes for the bacterial enzyme β-galactosidase (β-gal). From June 1994 through April 1995, six patients (five males and one female) were enrolled in the trial. A single dose of recombinant virus suspension containing 10 7 or 10 8 plaque-forming units (PFU) was injected intratumorally into two successive cohorts of three patients. Eligible patients received concomitant chemotherapy. Patients were kept under isolation conditions from 3 days before the injection was given until virus excretion was undetectable. Biopsyspecimens of the tumor and surrounding mucosa were collected on the 8th day and at 1, 2, and 3 months after injection. They were analyzed by cell culture, polymrase chain reaction (PCR), and β-gal expression for the presence of recombinant adenovirus. So that the risk of virus recombination or complementation could be minimized, wild-type adenovirus carriers among the hospital staff (identified by PCR) were excluded from contact with patients who were potentially excreting recombinant virus. β-gal was expressed in tumor biopsy specimens of three patients (one who received the 10 7 PFU dose level and two who received 10 8 ). Bronchoalveolar lavage specimens collected immediately after injection were positive for recombinant adenovirus when analyzed in culture and by PCR. All biologic fluids were negative for recombinant virus as judged by PCR after day 12, with the exception of bronchoalveolar lavage specimens (positive PCR up to 90 days in two of three patients treated with 10 8 PFU). The blood samples obtained from the three patients treated with 10 8 PFU showed positive PCR results immediately after virus injection. Patients were kept in isolation for a median of 17 days. The most common toxic effects were moderate bleeding (occurring in two patients) during bronchoscopy and fever (seen in four patients). Endoscopic and clinically objective antitumor responses were seen in four patients, including one patient who showed a complete response by pathologic evaluation. The median survival for the patients was 12.5 months (range, 3–16+ months). Throughout the study, hospital staff remained negative for recombinant adenovirus infection. This ongoing phase I study has demonstrated that a recombinant adenovirus-mediated marker gene, such as rAd.RSVβ-gal, can be safely introduced into humans and that the gene product is expressed by lung tumor cells of the host. [J Natl cancer Inst 1996;88:1857–63]
Endobronchial ultrasound-guided fine-needle aspiration (EBUS-FNA) of mediastinal lymph nodes is a minimally invasive and efficient tool for both diagnosis and staging of lung cancer. EBUS-FNA also permits tumor genotyping. However this critical datum for the therapeutic management is often long to obtain for metastatic patients with short life expectancy.From May 2011 to December 2017, 398 lung cancer patients underwent a genetic analysis based on EBUS-FNA samples. EBUS-FNAs were performed with rapid on-site evaluation. Mutations were studied with Sanger or new generation sequencing. Forty-three cases were also tested with a fully automated real-time PCR rapid technique. ALK abnormalities were assessed by immunohistochemistry and/or in situ hybridization.A genotypic result could be obtained in 316 cases (79.4%) and in 180 of the 198 more recent cases (90.9%). Genetic abnormalities were observed in 191 cases (48.0%). Using the rapid technique, EGFR/KRAS mutational status was obtained within a few hours following the histological diagnosis and on the same day of the EBUS-FNA by analyzing fresh specimens after intra-operative cytological diagnosis.In term of molecular diagnosis, EBUS-FNA provides high-quality biological material similar to that of other clinical sampling methods. Furthermore, our study suggests that a rapid molecular diagnostic method could lead to a prompt and appropriate therapeutic management for many advanced stage patients.
Surgical resection of pulmonary metastases (PMs) has been shown to produce approximately a 35% 5-year survival rate, but specific data about late survival are not available in the literature.A retrospective review and survival analysis of 186 adult patients who underwent surgery for PMs at a single center before June 1984 is presented.Of the 186 patients who had surgery, of whom 34 (18%) had an incomplete resection, the 10-year survival rate (Kaplan-Meier) was 23% (95% CI, 16-30%), and 36 patients, with PMs from nine different primary sites, were still at risk at 10 years. Two patients died of their primary disease more than 10 years after the first thoracotomy, and two are alive with uncontrolled disease. Thirty-one patients are currently alive and disease free. Comparison between the 36 10-year survivors and the 150 nonsurvivors revealed that only the percentage of incomplete resections and the mean number of resections per patient were significantly different between the two groups (P < 0.001); the histologic type of the primary tumor, the disease-free interval, and the number of resected PMs at the first thoracotomy were not found to be statistically significant prognostic factors.The 23% 10-year survival and the high rate of disease free 10-year survivors in this study constitute support for complete resection as an efficient therapeutic approach in patients with isolated PMs. Relevant criteria to select more precisely those patients who will benefit from resection remain to be developed.
