Management of Progressive Pulmonary Nodules Found during and outside of CT Lung Cancer Screening Studies.

Although the effectiveness of screening for lung cancer remains controversial, it is a fact that most lung cancers are diagnosed at an advanced stage outside of lung cancer screening programs. In 2013, the U.S. Preventive Services Task Force revised its lung cancer screening recommendation, now supporting lung cancer screening by low-dose computed tomography in patients at high risk. This is also endorsed by many major medical societies and advocacy group stakeholders, albeit with different eligibility criteria. In Europe, population-based lung cancer screening has so far not been recommended or implemented, as some important issues remain unresolved. Among them is the open question of how enlarging pulmonary nodules detected in lung cancer screening should be managed. This article comprises two parts: a review of the current lung cancer screening approaches and the potential therapeutic options for enlarging pulmonary nodules, followed by a meeting report including consensus statements of an interdisciplinary expert panel that discussed the potential of the different therapeutic options.

Epidermal growth factor receptor, HER-2/neu and related pathways in lung adenocarcinomas with bronchioloalveolar features.

Lung adenocarcinomas with bronchioalveolar features (ABAF), formerly called bronchioloalveolar cancers (BAC), constitute a distinct clinical, radiological and pathological entity among lung malignancies. Epidermal growth factor receptor (EGFR) and to a less extent, HER-2/neu, are known to be overexpressed in non-small lung cancers, but their exact status in ABAF is not well-documented. Stimulation of these two receptors results in the initiation of two major cascades, namely phosphatidylinositol 3-kinase (PI-3K) and Ras-dependent pathways. We have therefore studied the expressions of EGFR, HER-2/neu as well as phosphorylated AKT (pAKT) and phosphorylated extracellular-signal regulated kinase (ERK), which are key molecules in these two pathways, in 15 ABAF patients. EGFR was found to be overexpressed in 9 of 15 patients (60%). HER-2/neu overexpression was detected in 6 of the 14 tumors tested (43%). pAKT and pERK were both found to be positive in 13 of 15 patients (87%). Six of the seven tumors with mucinous pattern were negative for EGFR, while all of the other eight cases were positive (P=0.001). Mucinous tumors were also less likely than non-mucinous tumors to overexpress HER-2/neu (17% versus 63%, respectively). These findings suggest that ABAF, particularly those with non-mucinous histology, commonly harbors EGFR and HER-2/neu overexpression. PI-3K and Ras-dependant pathways that lie downstream are generally activated, even in the absence of EGFR and/or HER-2/neu overexpression. ABAF may be a particularly promising candidate for EGFR-targeted strategies and this possibility merits extensive evaluation in clinical trials.

Generation of diverse mutated tumor antigen-specific cytotoxic T lymphocytes in a lung cancer patient with long survival.

We have identified an antigen recognized on a large cell carcinoma of the lung by tumor-specific cytotoxic T lymphocytes (CTL). The antigenic peptide is encoded by a mutated alpha-actinin-4 gene and presented by human leukocyte antigen (HLA)-A2. Using HLA-A2-peptide tetramers, we have derived from patient peripheral blood lymphocytes (PBL) and autologous tumor infiltrating lymphocytes (TIL) several mutated alpha-actinin-4-specific T cell clones. These clones displayed similar tetramer staining but distinct T cell receptor (TCR) usage and antitumor reactivity. Indeed, TIL clones lysed more efficiently the autologous tumor cells and released higher cytokine levels than PBL clones. Importantly, treatment of cancer cells with interferon-gamma enhanced their susceptibility to PBL clone-mediated lysis correlated with increase in HLA-class I expression. The present findings provide evidence that an immune T cell response took place in a lung cancer patient with favorable clinical evolution and suggest that CTL, recognizing a truly tumor-specific antigen, may contribute to controlling the tumor.

Perspectives of novel imaging techniques for staging, therapy response assessment, and monitoring of surveillance in lung cancer: summary of the Dresden 2013 Post WCLC-IASLC State-of-the-Art Imaging Workshop.

Modern imaging techniques that can provide functional information on tumor vascularization, metabolic activity, or cellularity have seen significant improvements over the past decade. However, most of these techniques are currently not broadly utilized neither in clinical trials nor in clinical routine, although there is a large agreement on the fact that conventional approaches for therapy response assessment such as Response Evaluation Criteria in Solid Tumors or World Health Organization criteria-that exclusively focus on the change in tumor size-are of less value for response assessment in modern thoracic oncology. The aim of this article comprises two parts: a short review of the most promising state-of-the-art imaging techniques that have the potential to play a larger role in thoracic oncology within the near future followed by a meeting report including recommendations of an interdisciplinary expert panel that discussed the potential of the different techniques during the Dresden 2013 Post World Congress of Lung Cancer (WCLC)--International Association for the Study of Lung Cancer (IASLC) meeting. It is intended to provide a comprehensive summary about ongoing trends and future perspectives on functional imaging in thoracic oncology.

The potential role of surgery after induction treatment.

Induction treatment is the initial therapy that is administered before any locoregional procedure. In this article, the history of preoperative chemotherapy or chemoradiotherapy followed by induction chemoradiotherapy, in locally advanced non-small cell lung cancers (stages III A and B) is discussed, as well as the selection of an optimal subset of patients for induction strategies. In addition, the prognostic effects of response to treatment and/or surgical resection as recently reported in published clinical trials are analyzed. Finally, we conclude that mediastinal nodal downstaging after induction therapy significantly improves the survival of patients who are surgically resected after induction.

Radical en bloc resection for lung cancer invading the spine.

OBJECTIVE: We reviewed our 8-year experience with en bloc partial and total vertebrectomy for lung cancer invading the spine and report outcome and survival. METHODS: Nineteen patients with lung cancers involving the spine underwent en bloc resection. Eleven received induction treatment (chemotherapy, n = 5; chemoradiotherapy, n = 4; and radiation, n = 2). Pneumonectomy was performed in 3 patients, lobectomy in 13 patients, and wedge resection in 3 patients. Hemivertebrectomy was performed in 15 patients, and total vertebrectomy was performed in 4 patients. The median number of resected vertebral bodies was 3 (range, 1-4). Tumor stage was IIIB in 14 patients, IIIA in 1 patient, and IIB in 4 patients (hemivertebrectomy is performed in the case of T3 disease to obtain free margins). Surgical nodal status was N0 in 13 patients, N1 in 3 patients, N2 in 1 patient, and N3 (supraclavicular) in 2 patients. Complete macroscopic and microscopic resection was achieved in 15 (79%) patients. RESULTS: There was no immediate postoperative mortality. Morbidity was observed in 10 patients, including 4 (21%) complications related to the spinal surgery. The median hospital stay was 30 days. Seven patients were alive after a mean follow-up of 26 months (range, 7-74 months). The 1- and 5-year predicted survivals (updated) are 59% and 14%, respectively. Nine local recurrences were observed. CONCLUSIONS: En bloc resection of chest tumors with vertebrectomy is technically demanding, and postoperative morbidity should be critically addressed with this aggressive surgical intervention. However, an encouraging long-term survival observed in this series suggests that en bloc resection could be a valid option in selected patients with vertebral involvement of chest tumors.

Long-term results of endoscopic thoracic sympathectomy for upper limb hyperhidrosis.

BACKGROUND: Immediate results of endoscopic thoracic sympathectomy (ETS) for hyperhidrosis are good. Adverse effects are well known but are supposed to decrease with time. We report the long-term results of ETS with regard to efficacy, side effects and patient satisfaction. METHODS: From 1993 to 1998, 382 patients suffering from hyperhidrosis of the upper limbs were operated on by means of bilateral ETS. One hundred twenty-five could be reached. There were 91 females and 34 males with a mean age of 28 years. The mean follow-up was 3.8 years (range: 24 to 84 months). Patients answered a detailed questionnaire from an independent observer addressing the following issues: stability of the initial result, outcome of side effects, degree of satisfaction. RESULTS: The global recurrence rate was 8.8%: 6.6% for palmar hyperhidrosis and 65% for axillary hyperhidrosis. Compensatory sweating was observed in 86.4% of the patients. It was considered as minor by 61% of them, as embarrassing by 31.5%, and as disabling by 7.5%. Other reported side effects were: Horner's syndrome in 3 patients (2.4%), healing in 2 of them; chronic rhinitis in 3 (2.4%); gustatory sweating in 9 (7.2%); and hand dryness in 42%. Sixty-five percent of the patients were fully satisfied, 28.7% were globally satisfied, and 6.3% regretted the operation. Ninety-two percent of the patients claimed they would ask for the operation if it were to be redone. CONCLUSIONS: This study confirms that results of ETS are good and stable for palmar hyperhidrosis but deteriorate for axillary hyperhidrosis. Compensatory sweating does not improve with time and is the main cause of dissatisfaction. Recommendations drawn from these results are the following: (1) patients suffering from isolated axillary hyperhidrosis should rather be treated by local therapy; (2) patients should be better informed of adverse effects.

Full thoracoscopic approach for surgical management of invasive pulmonary aspergillosis.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a frequent and serious infection occurring in patients with hematologic malignancies and allogenic stem cell transplant (SCT) recipients, causing a high mortality rate. We report the use of full thoracoscopic management in 19 patients. METHODS: Nineteen patients (mean age 27 years) with diagnosed or probable IPA were operated on. Seventeen had an hematologic malignancy and 2 had a refractory aplastic anemia. Nine patients had undergone an allogenic SCT that was complicated by a graft-versus-host disease in 5 patients. In 3 patients, SCT was pending. All patients had preoperative systemic antifungal therapy for at least 2 weeks. Fifteen patients had only one lesion, whereas 4 had two lesions. Eight patients had an absolute neutrophil count less than 3,000 and 2 less than 1,000, and 9 were thrombopenic (platelet count <60,000) at the day of surgery. Wedge resections were performed in 7 patients and lobectomies were performed for the other 12. For the latter, an open approach via posterolateral thoracotomy was decided upon in only 1 patient. For the other 11 lobectomies, a mini-thoracotomy was needed in 3 cases for intraoperative difficulties. Conversion to conventional thoracotomy was necessary for 2 of these patients. In total, out of the 19 patients, 15 had a total endoscopic approach, 3 had a thoracotomy, and 1 had a video-assisted approach. RESULTS: There was no intraoperative mortality. In the group of wedge resections, no intraoperative or postoperative complication occurred. In the lobectomy group, three hemorrhages occurred during dissection of the pulmonary artery in the fissure, leading to conversion to a mini-thoracotomy in 2 patients and to a classic posterolateral thoracotomy in 1 patient. There were two minor complications: one pneumothorax and one mild pleural effusion. CONCLUSIONS: In these debilitated and immunocompromised patients, a full thoracoscopic resection of fungal infection is feasible, even for lobectomies. It allows a simpler postoperative course and minimizes sequelae.

Resection of lung carcinomas invading the mediastinum, including the superior vena cava.

Extended resection of lung carcinomas invading the superior vena cava was demonstrated to be feasible by several authors. This article describes these technically demanding procedures, with their short- and long-term results. In addition, current controversies are discussed concerning technical aspects, indications, outcomes, and classification of these locally advanced non-small cell lung cancers.

[Current insights in malignant pleural mesothelioma]. / Actualités dans le mésothéliome pleural malin.

Faced with the rising incidence of malignant pleural mesothelioma (MPM), the medical community is now busy to improve the care for this pathology. Although there is still no unanimously recognized therapy for MPM, long survival has been observed for some patients treated with associated therapies (surgery + radiotherapy + chemotherapy). However, the detection and the aggressive care of early stages MPM must be justified by a demonstrated survival improvement with conservation of a good quality of life. This article tries to summarize current insights concerning epidemiology, diagnosis and treatment of MPM. At now, more questions than responses exist concerning the care of this severe prognosis disease.

[Adjuvant chemotherapy in non-small cell lung cancer]. / Chimiothérapie adjuvante dans le cancer bronchique non à petites cellules.

Lung cancer is the leading cause of cancer death in France. Nearly 80% of lung tumors are non-small cell lung cancers (NSCLC). Surgery is the best curative approach, but it only concerns 30% of NSCLC, since the diagnosis is frequently made in patients with locally advanced or metastatic disease. Even when surgery is performed relapse occurs in up to 50% of patients. Several adjuvant trials have been led in the late 90's after an individual data-based meta-analysis suggested a 5% survival benefit at 5 years. Among those, the IALT study, with 1 867 patients included, confirms the benefit of post-operative chemotherapy in resected NSCLC. In this article, the current status of adjuvant chemotherapy is reviewed, and future prospects are discussed.

Cervical and retrosternal approach to the left thoracic cavity using a flexible endoscope.

OBJECTIVES: Mediastinoscopy remains the gold standard for surgical exploration of the mediastinum. The use of this approach to access the left thoracic cavity could be complicated by vascular or neurological lesion. The aim of this experimental work was to describe a new approach to the left thoracic cavity through a cervical incision and retrosternal space using a flexible endoscope as a unique instrument. METHODS: We conducted an experimental work on 12 refrigerated and non-embalmed cadavers. Through a cervical incision, we dissected the retrosternal space to the level of Louis angle and then opened the left mediastinal pleura. We introduced the flexible endoscope through this pleural window into the left thoracic cavity. We defined three distances between the borders of the endoscope entry point, the phrenic nerve and the mammary artery: Distance 1: between the medial edge of the endoscope entrance point and the medial edge of the left mammary artery, Distance 2: between the top of the endoscope entrance point and the penetration of phrenic nerve in the left thoracic cavity and Distance 3: between the lateral edge of the entrance point of the endoscope and the medial edge of the phrenic nerve. To measure these distances, we performed a left postero-lateral thoracotomy. RESULTS: Procedure was successfully executed in 10 of the 12 studied subjects. The mean distances 1, 2 and 3 were 17.1 (range 2-40), 39.5 (17-80) and 19.1 mm (10-40), respectively. The minimal Distance 1 was in two subjects 0.2 and 0.5 mm. CONCLUSIONS: This approach avoids the para-aortic and supra-aortic zone; this access could be less dangerous than already described access techniques. Despite the limits of our work on cadavers, and the two failures in the application of the access, the mean distances we calculated show the potential safety of our approach concerning the phrenic nerve and the mammary artery. An experimental protocol on living animals is currently underway with the aim of confirming the safety of our approach.

10-year long-term survival (LTS) of induction chemotherapy with three cycles cisplatin/paclitaxel followed by concurrent chemoradiation cisplatin/etoposide/45 Gy (1.5 Gy bid) plus surgery in locally advanced non-small-cell lung cancer (NSCLC)-a multicenter phase-II trial (CISTAXOL).

BACKGROUND: Induction chemoradiotherapy plus surgery remains an option to study in IIIA(N2) and selected IIIB NSCLC. Here we report ten-year long-term survival of a prospective multicenter German-French phase-II trial with trimodality. PATIENTS AND METHODS: Mediastinoscopically proven IIIA(N2)/selected IIIB NSCLC received three cycles cisplatin (50 mg/m(2) day 1+8) and paclitaxel (175 mg/m(2)d1) qd 22. Concurrent CTx/RTx followed: 45 Gy (1.5 Gy bid) with cisplatin 50 mg/m(2) day 2+9 and etoposide 100 mg/m(2) d 4-6. Surgery was planned three to five weeks after RTx. If evaluated inoperable/irresectable at the end of RTx, definitive RTx-boost (20 Gy; 2 Gy qd) followed. Here we report 10-year-LTS for this cohort. RESULTS: All 64 patients were accrued 3/99 to 2/02. Patients characteristics: IIIA(N2)/IIIB 25/39; m/f 48/16; adeno/squamous/large-cell/adenosquamous/NOS 15/26/18/3/2; age: median 52.5 (range 33-69). 36 operated: R0 32/36 (89%); pCR 16/36 (44%). 10-year-LTS%; all 26.0; IIIA(N2) 37.1; IIIB 17.9; relevant prognostic factors (exploratory): pretreatment - histopathology (squamous/adeno) - age (<50/≥50) - Charlson-CI: 1/>1 - BMI (≥25/<25) - pack years smoking (≥10/<10); treatment-dependent - R0/no-R0. CONCLUSIONS: This regimen achieves substantial LTS. Interestingly, adenocarcinomas, older patients, unfavorable comorbidity scores, higher BMI and light smokers demonstrate poor long-term outcome even with aggressive trimodality. This dataset defines the rationale for our ongoing randomized trial with surgery after induction therapy in IIIA(N2)/selected IIIB (ESPATÜ).

Diaphragm pacing after bilateral implantation of intradiaphragmatic phrenic stimulation electrodes through a transmediastinal endoscopic minimally invasive approach: pilot animal data.

OBJECTIVES: Phrenic nerve stimulation for diaphragm pacing allows patients with central respiratory paralysis to be weaned from mechanical ventilation. Two procedures are available, either intrathoracic (bilateral thoracotomy) or intradiaphragmatic (four ports laparoscopy). The present experimental work assesses the feasibility, safety and efficacy of a trans-mediastinal implantation of intradiaphragmatic phenic nerve stimulation electrodes using a flexible gastroscope through a cervical incision. METHODS: We operated on nine ewes. After selective bronchial intubation, we dissected the latero-tracheal space and opened both mediastinal pleura. We then introduced a flexible gastroscope into the pleural cavities, in a sequential manner. The phrenic nerves were located and followed up to the diaphragm dome. Electrodes loaded within a long, pliable needle were introduced through the adjacent intercostal space and implanted in each hemidiaphragm, at a 'tendinous' location (as close as possible to the entry of the nerve in the central tendon), and at a more lateral 'muscular' location. Postoperatively, the animals were ventilated using bilateral phrenic nerve stimulation. After euthanasia, abdominal verification of the electrodes position was performed through a laparotomy. RESULTS: The mediastinal and pleural parts of the procedure were uneventful. The insertion of electrodes was associated with transdiaphragmatic puncture and small abdominal haematomas in the first two animals studied. After a slight modification of the insertion technique, this was not observed anymore. Phrenic nerve stimulation produced efficient ventilation, with tidal volumes significantly higher when delivered at the tendinous site than at the muscular site. CONCLUSIONS: The trans-mediastinal implantation of intradiaphragmatic phrenic nerve stimulation electrodes is feasible, appears reasonably safe, and allows efficient ventilation.

Minimally invasive trans-mediastinal endoscopic approach to insert phrenic stimulation electrodes in the human diaphragm: a preliminary description in cadavers.

OBJECTIVE: Diaphragm pacing by phrenic nerve (PN) stimulation is currently used for patients with central respiratory paralysis to be weaned from mechanical ventilation. Electrodes are inserted either through bilateral thoracotomy or through four ports laparoscopy. The aim of this experimental work is to demonstrate the feasibility of trans-mediastinal bilateral implantation of PN electrodes using a flexible gastroscope introduced through a cervical incision in human cadavers. METHODS: Ten refrigerated and non-embalmed cadavers were used. The gastroscope was introduced through a cervical incision into the latero-tracheal space and then subsequently into both pleura by opening the mediastinal pleura. After identification of the PN, electrodes were introduced through an intercostal space to the desired diaphragmatic location using a long, pliable needle with the electrode loaded in its lumen. RESULTS: Results are described for each hemi-diaphragm not for an anatomic subject. Mediastinal exploration and introduction of the video gastroscope into the pleural cavities proved easy in all subjects. Pleural adherences were present in five hemi-diaphragms. The central tendon of both hemi-diaphragms could be identified unambiguously in all the subjects. Identification of the entry point of the phrenic nerve into the diaphragm was straightforward in 10 hemi-diaphragms. In the remaining 10, this proved more difficult because of mediastinal fat or lung parenchyma. Introduction of the electrode-holding needles through the intercostal space and their insertion close to the phrenic nerve entry point was also easy. Withdrawal of the needle from the diaphragm and 'capture' of the hook were successful on the first attempt in 14 hemi-diaphragms, but failed in six others in whom a second attempt was necessary. CONCLUSION: Trans-mediastinal implantation of PN stimulation electrodes is possible using a flexible endoscope. This application of endoscopic surgery could allow a minimally invasive placement of PN electrodes in patients with central respiratory paralysis, for example, at the time of tracheostomy.

Release of metal particles from needles used for transbronchial needle aspiration.

BACKGROUND: Although mediastinoscopy is still the gold standard for diagnosis of mediastinal lymphadenopathy, minimally invasive procedures have been developed: transbronchial needle aspiration (TBNA) using a flexible bronchoscope (conventional TBNA) or linear echoendoscope (endobronchial ultrasound [EBUS]) allowing real-time guided lymph node aspiration. The observation of contamination of samples by foreign particles led us to determine the frequency and the nature of this material and to identify its origin. METHODS: From June 2007 to November 2008, 141 consecutive patients underwent conventional TBNA (n = 84) or EBUS-guided TBNA (EBUS-TBNA) (n = 57). All cytologic samples were reviewed in blinded fashion, and contamination was assessed semiquantitatively. Mineral analysis using a transmission electron microscope equipped with an energy dispersive x-ray spectrometer was performed on the solution obtained after rinsing unused needles and on four samples of calf thymuses punctured with EBUS needles. RESULTS: Foreign material, different from anthracosis, was identified in samples obtained with five different batches of needles, only from EBUS-TBNA (P < .0001). The contamination score was correlated to the number of passes (P = .035). Mineral analyses of the rinsing solutions from conventional TBNA needles were negative, whereas metal alloys of iron, titanium, nickel, and chromium were released with EBUS needles. The same contamination was identified in three of the four punctured calf thymuses. CONCLUSIONS: Dedicated EBUS-TBNA needles are able to release metal particles, probably by friction between the stylet and the needle, with a potential risk to inject particles into nodes. The long-term consequences are unknown, but the need for safety measures should be evaluated.

Isolated rib metastases from renal cell carcinoma.

Osseous metastases of renal cell carcinoma (RCC) are the second most frequent location after lung metastases. They rarely present as isolated location. When isolated, resection may offer five-year survival rates of 30-60%. The purpose of the current study is to focus on a particular subset, the isolated rib metastases (IRM). The files of six patients who underwent radical resection for IRM were reviewed. All had previous radical nephrectomy for clear-cell renal cancer. The mean age of these six men was 55.3 years. Preoperative evaluation included in all patients a conventional chest radiograph and thoracic computed tomography (CT) scanning. Chest wall resections were wide and curative. The mean disease-free interval (DFI) after renal cancer treatment was 25 months. There was no postoperative death. Two patients had synchronous disease. One of them developed two recurrences operated on by large resections. They survived for 77 and 81 months. The overall five and ten-year survival rates were respectively, 83 and 66.7%. IRM of RCC are rare and remain not well-known. Surgical wide resection is a safe and effective treatment.

Cervical incision thoracic endoscopic surgery: a minimally invasive endoscopic approach in thoracic surgery.

Cervical incision thoracic surgery has recently been described. Currently, there is a move to increase the role of flexible endoscopy in surgery. The use of a flexible endoscope through a natural orifice into the thoracic cavity still remains ethically doubtful. The authors present a surgical experimental study using a flexible endoscope through a cervical incision for the exploration of both the mediastinum and the thoracic cavity in a cadaver. An experimental work on 10 refrigerated and non-embalmed cadavers was initiated. We used a unique device - a standard double-channel flexible video gastroscope. Through a small cervical incision, we performed simultaneous exploration of the mediastinum and both pleural cavities. Identification and biopsies of mediastinal lymph nodes at levels 2R, 4R, 7 and 4L were easy to perform in all subjects. In eight cadavers, we performed an assessment of bilateral pleural cavities and multiple pleural biopsies as well as bilateral thoracic sympathectomy. A chest tube was placed in the thoracic cavity at the end of all pleural procedures. The potential advantages of this approach are simultaneous exploration of the mediastinum and pleura and the performance of several thoracic interventions through a small cervical incision. The flexible endoscope could become a surgical tool for thoracic surgery.

Is neoadjuvant chemoradiotherapy a feasible strategy for stage IIIA-N2 non-small cell lung cancer? Mature results of the randomized IFCT-0101 phase II trial.

Locally advanced non-small cell lung cancers share a risk of both local and systemic recurrence and justifies a therapeutic strategy combining focal and systemic treatment. In resectable stage IIIA-N2 tumors, peri-operative chemotherapy significantly increases survival rates. Chemoradiotherapy, which is the standard treatment of non-resectable locally advanced tumors, may have a role as an induction treatment to reduce locoregional recurrence rates. In the present phase II trial, we aimed at comparing standard induction chemotherapy (arm A: cisplatin and gemcitabine) with 2 different regimens of induction chemoradiotherapy (total dose: 46 Gy) including third-generation cytotoxic agents (arm B: cisplatin and vinorelbine; arm C: carboplatin and paclitaxel) in patients with resectable stage IIIA-N2 NSCLC, using feasibility of the whole strategy, including surgery, as a primary endpoint. A total of 46 patients were included. Response rate was significantly higher after induction chemoradiotherapy vs. chemotherapy (87% vs. 57%, p=0.049). A total of 44 patients underwent operation. The feasibility rate of the proposed therapeutic strategy was 89% for the whole cohort, 93% in arm A (induction chemotherapy with cisplatin and gemcitabine), 88% in arm B (induction chemoradiotherapy with cisplatin and vinorelbine), and 87% in arm C (induction chemoradiotherapy with carboplatin and paclitaxel) (p=0.857). Overall median, 1-year, and 3-year survival were 30 months, 87%, and 43%, respectively. Induction chemoradiotherapy with modern treatment regimens is highly feasible and may show promises in the current and future developments of multimodal therapeutic strategies in locally advanced NSCLC.

Long-term results of the international adjuvant lung cancer trial evaluating adjuvant Cisplatin-based chemotherapy in resected lung cancer.

PURPOSE Based on 5-year or shorter-term follow-up data in recent randomized trials, adjuvant cisplatin-based chemotherapy is now generally recommended after complete surgical resection for patients with non-small-cell lung cancer (NSCLC). We evaluated the results of the International Adjuvant Lung Cancer Trial study with three additional years of follow-up. PATIENTS AND METHODS Patients with completely resected NSCLC were randomly assigned to three or four cycles of cisplatin-based chemotherapy or to observation. Cox models were used to evaluate treatment effect according to follow-up duration. Results The trial included 1,867 patients with a median follow-up of 7.5 years. Results showed a beneficial effect of adjuvant chemotherapy on overall survival (hazard ratio [HR], 0.91; 95% CI, 0.81 to 1.02; P = .10) and on disease-free survival (HR, 0.88; 95% CI, 0.78 to 0.98; P = .02). However, there was a significant difference between the results of overall survival before and after 5 years of follow-up (HR, 0.86; 95% CI, 0.76 to 0.97; P = .01 v HR, 1.45; 95% CI, 1.02 to 2.07; P = .04) with P = .006 for interaction. Similar results were observed for disease-free survival. The analysis of non-lung cancer deaths for the whole period showed an HR of 1.34 (95% CI, 0.99 to 1.81; P = .06). CONCLUSION These results confirm the significant efficacy of adjuvant chemotherapy at 5 years. The difference in results beyond 5 years of follow-up underscores the need for the long-term follow-up of other adjuvant lung cancer trials and for a better identification of patients deriving long-term benefit from adjuvant chemotherapy.