Surgical or medical strategy for locally-advanced, stage IIIA/B-N2 non-small cell lung cancer: Reproducibility of decision-making at a multidisciplinary tumor board.

BACKGROUND: Stage IIIA/B-N2 is a very heterogeneous group of patients and accounts for one third of NSCLC at diagnosis. The best treatment strategy is established at a Multidisciplinary Tumor Board (MTB): surgical resection with neoadjuvant or adjuvant therapy versus definitive chemoradiation with immune checkpoint inhibitors consolidation. Despite the crucial role of MTBs in this complex setting, limited data is available regarding its performances and the reproducibility of the decision-making. METHODS: Using a large cohort of IIIA/B-N2 NSCLC patients, we described patient's characteristics and treatment strategies established at the initial MTB: with a "surgical strategy" group, for potentially resectable disease, and a "medical strategy" group for non-resectable patients. A third group consisted of patients who were not eligible for surgery after neoadjuvant treatment and switched from the surgical to the medical strategy. We randomly selected 30 cases (10 in each of the 3 groups) for a blinded re-discussion at a fictive MTB and analyzed the reproducibility and factors associated with treatment decision. RESULTS: Ninety-seven IIIA/B-N2 NSCLC patients were enrolled between June 2017 and December 2019. The initial MTB opted for a medical or a surgical strategy in 44% and 56% of patients respectively. We identified histology, tumor size and localization, extent of lymph node involvement and the presence of bulky mediastinal nodes as key decision-making factors. Thirteen patients were not eligible for surgical resection after neoadjuvant therapy and switched for a medical strategy. Overall concordance between the initial decision and the re-discussion was 70%. The kappa correlation coefficient was 0.43. Concordance was higher for patients with limited mediastinal node invasion. Survival did not appear to be impacted by conflicting decisions. CONCLUSIONS: Reproducibility of treatment decision-making for stage IIIA/B-N2 NSCLC patients at a MTB is moderate but does not impact survival.

Neoadjuvant durvalumab for resectable non-small-cell lung cancer (NSCLC): results from a multicenter study (IFCT-1601 IONESCO).

BACKGROUND: The IONESCO (IFCT-1601) trial assessed the feasibility of neoadjuvant durvalumab, for early-stage resectable non-small-cell lung cancer (NSCLC). METHODS: In a multicenter, single-arm, phase II trial, patients with IB (≥4 cm)-IIIA, non-N2, resectable NSCLC received three doses of durvalumab (750 mg every 2 weeks) and underwent surgery between 2 and 14 days after the last infusion. The primary endpoint was the complete surgical resection rate. Secondary endpoints included tumor response rate, major histopathological response (MPR: ≤10% remaining viable tumor cells), disease-free survival (DFS), overall survival (OS), durvalumab-related safety, and 90-day postoperative mortality (NCT03030131). RESULTS: Forty-six patients were eligible (median age 60.9 years); 67% were male, 98% were smokers, and 41% had squamous cell carcinoma. Regarding tumor response, 9% had a partial response, 78% had stable disease, and 13% had progressive disease. Among the operated patients (n=43), 41 achieved complete resection (89%, 95% CI 80.1% to 98.1%)), and eight achieved MPR (19%). The 12-month median OS and DFS rates were 89% (95% CI 75.8% to 95.3%) and 78% (95% CI 63.4% to 87.7%), respectively (n=46). The median follow-up was 28.4 months (12.8-41.1). All patients in whom MPR was achieved were disease-free at 12 months compared to only 11% of those with >10% residual tumor cells (p=0.04). No durvalumab-related serious or grade 3-5 events were reported. The unexpected 90-day postoperative mortality of four patients led to premature study termination. None of these four deaths was considered secondary to direct durvalumab-related toxicity. CONCLUSIONS: Neoadjuvant durvalumab given as monotherapy was associated with an 89% complete resection rate and an MPR of 19%. Despite an unexpectedly high rate of postoperative deaths, which prevented us from completing the trial, we were able to show a significant association between MPR and DFS.

Electromagnetic navigation bronchoscopy localization of lung nodules for thoracoscopic resection.

BACKGROUND: Thoracoscopic localization of small peripheral pulmonary nodules is a concern. Failure can lead to larger parenchymal resection or conversion to thoracotomy. This study evaluates our experience in preoperative electromagnetic navigation bronchoscopy-guided localization of small peripheral lung lesions. METHODS: From January 2017 to March 2020 clinical, radiographic, surgical, and pathological data of patients who underwent electromagnetic navigation bronchoscopy (ENB)-guided methylene blue pleural marking of highly suspected pulmonary lesions before a full thoracoscopic resection were evaluated. Localization was performed for solid or mixed subpleural nodules measuring <10 mm, solid nodules measuring <20 mm located at more than 1 cm from the pleura and any pure ground glass opacity. Successful localization was defined as successful identification and thoracoscopic resection of target lesions. RESULTS: Forty-eight patients were included: 30 solid nodules (63%), 12 pure GGO (25%) and 6 mixed (13%). The median largest diameter at CT-scan was 11 mm (IQR, 9-14 mm) while the median distance from the pleural surface was 12 mm (IQR, 6-16 mm). The median ENB length was 25 min (19-33 min). Localization procedure was successful in 45 cases (94%). No procedural-related complications were reported. CONCLUSIONS: ENB is a safe and accurate preoperative procedure to localize small lung peripheral lesions. The high successful rate, the absence of related complications, the possibility of performing the procedure in the same operating room with a single general anesthesia, make ENB-guided dye marking an advantageous tool for thoracoscopic pulmonary resection.

Sensitivity of Cytology Specimens From Bronchial Aspirate or Washing During Bronchoscopy in the Diagnosis of Lung Malignancies: An Update.

BACKGROUND: Routine collection of cytology specimens from bronchial aspirate or washing is thought to increase the sensitivity of bronchoscopy for diagnosing malignant lung lesions. However, the added value of this practice has not been reappraised in a context of changing epidemiology. PATIENTS AND METHODS: In a retrospective monocenter study, all cytology specimens from bronchial aspirate or washing collected between May 2011 and December 2014 and the corresponding patients' files were reviewed. The final diagnosis of malignancy was based on all available pathologic information. RESULTS: Bronchoscopy was performed in 2750 patients, and bronchial cytology specimens were collected during 667 procedures, including 474 aspirate or washing cytology specimens collected during conventional (n = 366) or ultrasound-guided (EBUS) (n = 108) bronchoscopy in 455 patients with malignant lung lesion(s). The predominant histologic types were lung adenocarcinoma (43.9%) and squamous cell carcinoma (25.2%), and 271 tumors (59.6%) were endoscopically visible. At least 1 endoscopic sample (bronchial cytology and/or biopsies and/or endobronchial ultrasound-guided samples) was positive for malignancy during 329 (69.4%) of the 474 endoscopies, including 79 samples obtained in nonvisible lesions. Only 67 bronchial cytology specimens proved positive (sensitivity, 14.7%; 95% confidence interval, 11.8%-18.3%), and only 1 specimen (0.2%) produced a diagnosis not made by other samples during the same procedure. CONCLUSION: In contrast with older studies, the added value of collecting cytology specimens from bronchial aspirate or washing during bronchoscopy in this series proved negligible, reflecting mainly the increasing prevalence of adenocarcinomas. Abandoning this technique could be considered in centers with similar expertise and patient populations.

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.

[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.

Bulky mediastinal aspergillosis mimicking cancer in an immunocompetent patient.

We describe the case of a previously healthy 42-year-old woman who presented with a chronic cough and occasional night sweats. Radiologic exploration showed a bulky mediastinal mass surrounding the aortic arch, associated with a left subclavicular lymph node and a cerebral round lesion, mimicking a disseminated lung cancer. Surgical left subclavicular and computed tomography-guided mediastinal biopsy specimens showed granulomatous patterns. Mycologic culture of both samples grew Aspergillus flavus. Resolution was obtained after 9 months of oral voriconazole therapy.

Transfusions, major bleeding, and prevention of venous thromboembolism with enoxaparin or fondaparinux in thoracic surgery.

Enoxaparin 40 mg/day (E) or fondaparinux 2.5 mg/day (F) are recommended to prevent venous thromboembolism (VTE) in medical and surgical patients at risk. Over the two years after switching from E to F in our 35-bed department of pulmonology and thoracic surgery, an increase in the number of transfusions was observed. A retrospective explanatory investigation was undertaken. Hospitalised patients in the two years before and after switching from E to F were compared. The files of all transfused patients were reviewed. A blinded independent committee adjudicated major bleeding events. In the investigated time period, the overall transfusion rate increased from 1.8% of 2,989 patients to 3.1% of 3,085 patients (p=0.002). Mean ages (58.4 vs. 59.1 years), proportions of surgical patients (63.6% vs. 58.4%), cancer patients (72.1% vs. 69.5%), and treated patients (≥ 1 dose of E or F: 51.8% vs. 52.5%) were similar. The number of medical patients transfused while receiving E or F did not increase significantly (0.9% vs. 1.3%, RR=1.45 [0.66-3.17], p=0.35). The number of surgical patients transfused postoperatively while receiving E or F increased significantly (0.7% vs. 1.9% of all surgical patients, relative risk [RR]=2.75 [1.45-5.23], p=0.001), including a significant increase in transfusions for major bleeding (0.2% vs. 0.9%, RR=5.97 [1.74-20.4], p<0.001). A multivariate analysis did not find confounding factors. The incidence of symptomatic postoperative pulmonary embolism remained very low (0.05% vs. 0.17%). In conclusion, in thoracic surgery patients, switching from enoxaparin to fondaparinux to prevent VTE was associated with a significant increase in the risk of postoperative major bleeding. A causal relationship appears plausible.

Combined etoposide, ifosfamide, and cisplatin in the treatment of patients with advanced thymoma and thymic carcinoma. A French experience.

INTRODUCTION: The value of a nonanthracyclin regimen in thymic carcinoma and malignant thymoma is not well defined. These regimens may be useful in some patients, particularly with cardiac diseases. The objective of this study is to evaluate the response rate, progression free survival, overall survival and toxicity of combined etoposide, ifosfamide, and cisplatin in patients with advanced thymoma and thymic carcinoma. METHODS: From October 1995 to April 2001, 18 patients with advanced thymoma or thymic carcinoma were entered on trial, and receive etoposide (100 mg/m(2) on days 1-3), ifosfamide (1500 mg/m(2) on days 1-3), s and cisplatin (30 mg/m(2) on days 1-3). Cycles were repeated every 3 weeks for a total of six cycles. RESULTS: Among 16 evaluable patients, there were no complete responses and four partial responses (complete and partial responses rate, 25%; confidence interval [CI] 95, 7-48%). The median follow-up was 32.6 months (range, <9-84 months), and the median overall survival has not yet been reached because more than 50% of patients are still alive. Based on Kaplan-Meier estimates, the 1-year and 2-year survival rates were 93.8 and 78.1%, respectively. The toxicity was predominantly myelosuppresion and alopecia. CONCLUSIONS: The combined etoposide, ifosfamide, and cisplatin regimen has moderate activity in patients with advanced thymic tumors. Our results confirm the Eastern Cooperative Oncology Group trial published in 2001. Response rates appear to be lower to many phase II trials, but survival seems similar.

Spontaneous middle lobe torsion secondary to pleural effusion.

Pulmonary torsion is very rare, and usually occurs following lung resection. We report a case of spontaneous middle lobe torsion in a patient presenting with a right pleural effusion. The condition was treated by lobectomy through a totally thoracoscopic approach.

Uncertain benefit from surgery in patients with lung metastases from breast carcinoma.

BACKGROUND: Isolated lung metastases have been reported to occur in 10-20% of all women with breast carcinoma. The authors described a series of patients who underwent surgery for lung metastases from breast carcinoma. METHODS: They reviewed the files of 125 consecutive patients who underwent surgery with a curative intent for lung metastases from breast carcinoma between 1972 an 1998 at a single institution. Survival curves were plotted by the Kaplan-Meier method. Prognostic factors were identified using the log-rank test and a Cox proportional hazards model for univariate and multivariate analyses, respectively. RESULTS: The median age at surgery was 53 years. There was a median of 1 resected metastasis (range, 1-16 resected metastases). The median size of the largest metastasis was 19 mm (range, 5-70 mm). The median disease-free interval (DFI) was 3 years. The median follow-up time after surgery was 8.5 years (range, 25 days to 22 years). The 3-year, 5-year, and 10-year probabilities of survival were 58% (95% confidence interval [95% CI], 49-67%), 45% (95% CI, 36-55%), and 30% (95% CI, 21-41%), respectively. The median survival time after surgery was 4.2 years. Complete resection was achieved in 96 patients. The quality of the resection (complete vs. incomplete) was not a statistically significant prognostic factor by univariate analysis and there was no significant difference between these two groups in terms of adjuvant postoperative therapy. The characteristics of the primary tumor and the number of metastases (one vs. two or more) had no detectable influence on survival. The size of the largest metastasis (> 20 mm or < or = 20 mm) and the DFI (< or = 3 years vs. > 3 years) were highly significant prognostic factors (P = 0.006 and P = 0.003, respectively). This was confirmed by multivariate analysis. Patients with a DFI < or = 3 years and/or the largest metastasis > 20 mm reportedly had a poor outcome (median survival, 2.6 years vs. 8.5 years for patients with none of these poor prognostic factors). CONCLUSIONS: Resection of lung metastases from breast carcinoma was associated with a significant 5-year survival rate of 45%. Whether these encouraging findings resulted from the surgical procedure itself or the preoperative selection of patients remained uncertain. When surgery is considered in this setting, the size of the largest metastasis and the DFI should be taken into account.

Thoracoscopic management of postpneumonectomy empyema.

BACKGROUND: Even when there is no associated bronchopleural fistula, empyema is a serious complication of pneumonectomy. Aggressive surgical treatments are usually applied. However, a minimally invasive approach might achieve satisfactory results in selected patients. METHODS: Out of 17 patients presenting with a postpneumonectomy empyema (PPE), 11 had a thoracoscopic approach. There were 9 males and 2 females, (age, 38-74; mean, 59 years). Ten patients had no proven bronchopleural fistula (BPF). One of them had a minor (< 3 mm) BPF. Empyema was confirmed by thoracentesis and bacteriological examination. All patients had immediate chest tube drainage and underwent emergency thoracoscopic debridement of the empyema. No irrigation was used postoperatively. RESULTS: There was no mortality and no morbidity related to the procedure. The average duration of thoracoscopic debridement was 62 minutes (range: 45-80 minutes). In 8 patients the chest tube was removed between the fifth and thirteenth postoperative day (average, 8.6 days). They were discharged between the 9th and 24th postoperative day. In 3 patients, clinical and/or biological signs of infection persisted and reoperation was decided at day 5, day 10, and day 11. All 3 patients underwent open-window thoracostomy. The average follow-up of the 8 patients who underwent only thoracoscopy was 10 months (range, 2-27 months). None had recurrent empyema. The patient who presented with a minor BPF remained asymptomatic and is doing well after a 27 month follow-up. CONCLUSIONS: Thoracoscopy might be a valuable approach for patients presenting with PPE with or without minor bronchopleural fistula.