Lung cancer, including both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), remains one of the most aggressive types of cancer, and the prognosis for individuals diagnosed with ...this neoplasm has, for the most part, been insufficient ....
Causing a high mortality rate worldwide, lung cancer remains an incurable malignancy resistant to conventional therapy. Despite the discovery of specific molecular targets and new treatment ...strategies, there remains a pressing need to develop more efficient therapy to further improve the management of this disease. Cancer stem cells (CSCs) are considered the root of sustained tumor growth. This consensus corroborates the CSC model asserting that a distinct subpopulation of malignant cells within a tumor drives and maintains tumor progression with high heterogeneity. Besides being highly tumorigenic, CSCs are highly refractory to standard drugs; therefore, cancer treatment should be focused on eliminating these cells. Herein, we present the current knowledge of the existence of CSCs, CSC-associated mechanisms of chemoresistance, the ability of CSCs to evade immune surveillance, and potential CSC inhibitors in lung cancer, to provide a wider insight to drive a more efficient elimination of this pro-oncogenic and treatment-resistant cell fraction.
Despite tremendous efforts to improve the treatment of lung cancer, prognosis still remains poor; hence, the search for efficacious therapeutic option remains a prime concern in lung cancer research. ...Cell cycle regulation including mitosis has emerged as an important target for cancer management. Novel pharmacological agents blocking the activities of regulatory molecules that control the functional aspects of mitosis such as Aurora kinases are now being investigated. The Aurora kinases, Aurora-A (AURKA), and Aurora B (AURKB) are overexpressed in many tumor entities such as lung cancer that correlate with poor survival, whereby their inhibition, in most cases, enhances the efficacy of chemo-and radiotherapies, indicating their implication in cancer therapy. The current knowledge on Aurora kinase inhibitors has increasingly shown high potential in ensuing targeted therapies in lung malignancies. In this review, we will briefly describe the biology of Aurora kinases, highlight their oncogenic roles in the pre-clinical and clinical studies in lung cancer and, finally, address the challenges and potentials of Aurora kinases to improve the therapy of this malignancy.
Abstract
Background
Intrathoracic neurogenic tumors (INTs) are uncommon neoplasms arising from nerve tissues. We report our single-center experience in treating these rare INTs.
Methods
Using a ...prospective institutional database, clinical, surgical, and pathological records of patients receiving resection of INT between May 1998 and June 2018 were analyzed. Survival was calculated by Kaplan–Meier method.
Results
There were 82 patients (24 females) with an average age of 53 years (29–75 years). Mean diameter was 32 mm (range, 12–68 mm). Histology included 49 schwannomas (11 malignant), 15 neurinomas (2 malignant), 14 neurilemmomas, and 4 paragangliomas. Tumor was located in the posterior mediastinum in 52 patients, in the thoracic inlet in 12, in the anterior mediastinum in 7, in the lung parenchyma in 5, and in the chest wall in 3. In three (3.6%) patients, the tumor showed an intraspinal extension. Symptoms were reported in 51 patients (62.2%) and included cough in 23, dyspnea in 15, neurologic symptoms in 11, and wheezing in 2. Operation was performed by thoracotomy in 42 (51.2%) cases and less invasive technique in 40 (48.8%) cases. Resection was completed in 80 patients (97.6%). Postoperative radiotherapy was administered in two cases. Intraoperative and postoperative mortalities were nil. Morbidity occurred in four patients (4.8%) including two prolonged air leaks, one hemothorax, and one chylothorax. Five-year survival was 97% (mean follow-up, 4.9 years). Malignant tumors had a worse prognosis (
p
= 0.02). No recurrence occurred during the follow-up neither for malignant nor for benign tumors.
Conclusion
The treatment of choice for INTs is complete resection which will be tailored to tumor size, location, and extension. Long-term prognosis is favorable for benign neurogenic tumors.
After a variable period of activity of the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment, patients with advanced non-small cell lung cancer (NSCLC) harboring
...mutations develop resistance to these TKIs. In some cases, an oligoprogression is diagnosed, and its management is still controversial. The oligoprogression represents an intermediate stage of metastatic NSCLC between localized and widely disseminated disease, and is characterized by a limited number and/or sites of metastases in which a disease progression appears, together with a more indolent tumor biology. Currently, the management of oligoprogressed NSCLC involves local treatment, including radiotherapy and/or surgery, to control the progressive lesions. Systemic therapy should also be a potential approach to boost the activity of EGFR-TKIs. However, considering the lack of large trials addressing this topic, the optimal therapeutic strategies remain undefined and should be evaluated on an individualized basis. In this paper, we review the most relevant scientific evidence of continuing the systemic therapy with the same EGFR-TKI for the management of patients with NSCLC harboring EGFR mutations and oligoprogressed to first-line EGFR-TKIs, also discussing the controversies and potential future directions.
Background: Completion pneumonectomy (CP) is associated with high morbidity and mortality. We reviewed our experience to evaluate whether induction treatment (IT) may affect postoperative outcomes ...and analyzed factors influencing long-term results. Methods: Between 1998 and 2020, 69 patients with lung cancer underwent CP (50 males, median age 63 years, right CP in 47 patients). A total of 23 patients (33.3%) received IT (chemotherapy in 15, chemoradiotherapy in 7, and radiation in 1). Surgery included 25 (36.2%) extended resections and five (7.2%) tracheal sleeve CP. Results: The 30-day mortality rate was 7.2% (5/69), and overall morbidity was 37.6%. Major complications occurred in five patients (7.2%): one cardiac dislocation, one diaphragmatic hernia, one transient ischemic attack (TIA), and two bronchopleural fistulas. Minor complications occurred in 21 cases (30.4%): pulmonary in 12, cardiac in 7, and neurological in 2. The median hospital stay was 8 days (range, 5–56 days). IT did not influence postoperative morbidity and mortality. Pathological staging included 19 (27.5%) stage I, 36 (52.2%) stage II, and 14 (20.3%) stage III. Overall 5-year survival was 51.7%. Factors influencing survival were IT (p = 0.01), extension of resection (p = 0.04), histology (p = 0.01), pathological stage (p = 0.03), and T and N factors (p = 0.2, respectively). Factors affecting survival in multivariate analysis included IT (p = 0.02) and histology (p = 0.03). Conclusions: In our experience, CP had a low mortality, acceptable morbidity, and good long-term survival, which justifies this surgical procedure. Postoperative complications were not influenced by IT. Long-term survival was adversely influenced by the absence of IT, the presence of extended resection, the presence of squamous cell carcinoma, and cancers at advanced stages.
Background Screening programs have increased the identification of small or indistinct pulmonary lesions that are difficult to localize. We report our experience in their preoperative localization by ...radiotracer and resection. Methods Patients with pulmonary nodules of subsolid morphology or smaller than 1 cm, deeper 1 cm below the visceral pleura, or both underwent computed tomography (CT)-guided injection of radiotracer technetium 99m macroaggregates in the vicinity of the lesion. During the operation, a handheld gamma probe was used to detect the hot spot where the radioactive tracer was localized, and this area was resected. Results From November 2007 to May 2013, 112 patients (58 men; median age 62 years) underwent preoperative radiotracer injection with a successful marking in all patients. Adverse events included 33 (29.4%) pneumothoraces (one requiring chest tube placement), 23 (20.5%) parenchymal hemorrhage suffusions, and 1 (0.9%) allergic reaction to contrast medium. In all cases except two, the gamma probe revealed pulmonary lesions. Overall, 123 pulmonary nodules were localized and resected. The mean distance from the pleura was 12 mm (range, 0 to 39 mm). Pulmonary resection was performed by thoracoscopy in 70 (62.5%) cases, thoracotomy in 36 (32.1%), and conversion of thoracoscopy to thoracotomy in 6 (5.4%). The mean nodule size was 9 mm (range, 3 to 24 mm). Histology showed 14 (11.4%) benign lesions and 109 (88.6%) malignant lesions (85 primary lung cancers and 24 metastases). Conclusions Radiotracer localization of pulmonary lesions is a simple and feasible procedure with a high rate of success. Optimal candidates are patients with suspicious-looking nodules detected by screening or incidental CT resulting frm the high rate of nonsolid morphology and small size.
Background
Lung cancer is one of the most challenging diseases to treat. In the past decades standard therapy including surgery, chemo- and radiation therapy, alone or in combination has not changed ...the high mortality rate and poor prognosis. In recent years, mesenchymal stem cells (MSCs) have emerged as putative therapeutic tools due to their intrinsic tumor tropism, anti-tumor and immunoregulatory properties. MSCs release biomolecules that are thought to exert the same beneficial effects as their cellular counterparts and, as such, they may offer practical possibilities of using MSC-secreted products. Owing to their innate affinity to home to tumor sites, MSCs have also gained interest as selective vehicles for the delivery of anti-cancer agents. However, MSCs are also known to confer pro-oncogenic effects, rendering them into double-sword weapons against neoplastic diseases.
Conclusions
Here, we present published data on the cell- and secretome-based therapeutic competences of MSCs, as well as on their potential as engineered delivery vectors for the treatment of lung cancer. Despite the controversial role of MSCs in the context of lung cancer therapy, current findings support hopeful perspectives to harness the potential of MSC-based regimens that may augment current treatment modalities in lung cancer.
Four-arm robotic lobectomy for the treatment of early-stage lung cancer Veronesi, Giulia, MD; Galetta, Domenico, MD; Maisonneuve, Patrick, DipEng ...
Journal of thoracic and cardiovascular surgery/The Journal of thoracic and cardiovascular surgery/The journal of thoracic and cardiovascular surgery,
07/2010, Letnik:
140, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Objectives We investigated the feasibility and safety of four-arm robotic lung lobectomy in patients with lung cancer and described the robotic lobectomy technique with mediastinal lymph node ...dissection. Methods Over 21 months, 54 patients underwent robotic lobectomy for early-stage lung cancer at our institute. We used a da Vinci Robotic System (Intuitive Surgical, Inc, Mountain View, Calif) with three ports plus one utility incision to isolate hilum elements and perform vascular and bronchial resection using standard endoscopic staplers. Standard mediastinal lymph node dissection was performed subsequently. Surgical outcomes were compared with those in 54 patients who underwent open surgery over the same period and were matched to the robotic group using propensity scores for a series of preoperative variables. Results Conversion to open surgery was necessary in 7 (13%) cases. Postoperative complications (11/54, 20%, in each group) and median number of lymph nodes removed (17.5 robotic vs 17 open) were similar in the 2 groups. Median robotic operating time decreased by 43 minutes ( P = .02) from first tertile (18 patients) to the second-plus-third tertile (36 patients). Median postoperative hospitalization was significantly shorter after robotic (excluding first tertile) than after open operations (4.5 days vs 6 days; P = .002). Conclusions Robotic lobectomy with lymph node dissection is practicable, safe, and associated with shorter postoperative hospitalization than open surgery. From the number of lymph nodes removed it also appears oncologically acceptable for early lung cancer. Benefits in terms of postoperative pain, respiratory function, and quality of life still require evaluation. We expect that technologic developments will further simplify the robotic procedure.
-deregulated NSCLC represents an urgent clinical need because of unfavorable prognosis and lack of specific therapies. Although recent studies have suggested a potential role for crizotinib in ...patients harboring
amplification or exon 14 mutations, no conclusive data are currently available. This study aimed at investigating activity of crizotinib in patients harboring
or
alterations.
Patients with pretreated advanced NSCLC and evidence of
rearrangements (cohort A) or
deregulation (amplification, ratio MET/CEP7 >2.2 or
exon 14 mutations, cohort B) were treated with crizotinib 250 mg twice daily orally. The coprimary endpoint was objective response rate in the two cohorts.
From December 2014 to March 2017, 505 patients were screened and a total of 52 patients (26 patients per cohort) were enrolled onto the study. At data cutoff of September 2017, in cohort A, objective response rate was 65%, and median progression-free survival and overall survival were 22.8 months 95% confidence interval (CI) 15.2-30.3 and not reached, respectively. In cohort B, objective response rate was 27%, median progression-free survival was 4.4 months (95% CI 3.0-5.8), and overall survival was 5.4 months (95% CI, 4.2-6.5). No difference in any clinical endpoint was observed between
-amplified and exon 14-mutated patients. No response was observed among the 5 patients with cooccurrence of a second gene alteration. No unexpected toxicity was observed in both cohorts.
Crizotinib induces response in a fraction of
-deregulated NSCLC. Additional studies and innovative therapies are urgently needed.
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