What is early lung cancer? A review of the literature

The dismal cure rate of patients with lung cancer and the stage shift hypothesis have propelled the interest to perform screening at large, despite that previous randomized clinical trials failed to show any mortality benefit and the controversial issue of overdiagnosis. Due to early detection programs, a larger number of individuals at risk will be found to harbor small and potentially malignant early stage lesions. The application of non- and minimal invasive techniques for early detection, staging and treatment will become increasingly important. This review deals with the available clinical, surgical and pathological data focusing on early lung cancer lesions < or =1 cm. Literature data from both centrally located and parenchymal lesions < or =3 cm. have been analyzed. For all sub-centimeter lesions, minimal invasive staging and treatment approaches must still be considered inappropriate. Less invasive and less extensive treatment methods may be considered in high risk individuals with < or =1 cm. peripheral lesion showing > or =50 ground glass opacity on high resolution CT scan and those with superficial lesion in their central airways without deeper tumor invasion in the bronchial wall. Caution is necessary, however, as clinical staging remains inferior to pathological staging which is based on tissue samples collected after complete tumor removal and mediastinal lymph nodes dissection have been performed.     

Is there a role of nab-paclitaxel in the treatment of advanced non-small cell lung cancer? The data suggest yes

Nab-paclitaxel is a novel therapeutic agent, which was approved in combination with carboplatin in the first-line treatment of advanced non-small cell lung cancer (NSCLC) regardless of histologic subtype in the United States of America by the Food and Drug Administration in 2012 and by the European Commission in 2015. This approval was based on the results of a phase III clinical trial showing superior response rates compared with solvent-based paclitaxel in combination with carboplatin. This review will focus on the early development and clinical data to date supporting the use of nab-paclitaxel in advanced NSCLC. The clinical question central to this review is whether nab-paclitaxel has a place in the current therapeutic landscape of advanced NSCLC.     

Is there an optimal time to initiate adjuvant chemotherapy to predict benefit of survival in non-small cell lung cancer?

Objective:Adjuvant chemotherapy (AC) after curative resection is known to improve the survival of patients with non-small cell lung cancer (NSCLC);however,few studies have reported the correlation between the time to initiation ofAC (TTAC) and survival in NSCLC patients.Methods:The clinical data of 925 NSCLC patients who received curative resection and post-operative AC at the Cancer Hospital of Chinese Academy of Medical Sciences between 2003 and 2013 were retrospectively analyzed.TTAC was measured from the date of surgery to the initiation of AC.Disease-free survival (DFS) was defined as the duration from surgery to the time of tumor recurrence or last follow-up evaluation.The optimal cut-off value of TTAC was determined by maximally selected log-rank statistics.The DFS curve was estimated using the Kaplan-Meier method,and the Cox proportional hazards regression model was used to identify risk factors independently associated with DFS.Propensity score matching (PSM) was performed for survival analysis using the match data.Results:The optimal discriminating cut-off value of TTAC was set at d 3 5 after curative resection based on which the patients were assigned into two groups:group A (≤35 d) and group B (＞35 d).There was no significant difference in the DFS between the two groups (P=0.246),indicating that the TTAC is not an independent prognostic factor for DFS.A further comparison continued to show no significant difference in the DFS among 258 PSM pairs (P=0.283).Conclusions:There was no significant correlation between the TTAC and DFS in NSCLC patents.Studies with larger samples are needed to further verify this conclusion.     

Exercise training for people following lung resection for non-small cell lung cancer – A Cochrane systematic review

Objectives

To determine the effects of exercise training on exercise capacity, health-related quality of life (HRQoL), lung function (forced expiratory volume in one second (FEV₁)) and quadriceps force in people who have had a recent lung resection for non-small cell lung cancer (NSCLC).

Data sources

We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, SciELO and PEDro up to February 2013.

Review methods

We included randomised controlled trials (RCTs) in which study participants with NSCLC, who had recently undergone lung resection, were allocated to receive either exercise training or no exercise training. Two review authors screened and identified the studies for inclusion.

Results

We identified three RCTs involving 178 participants. On completion of the intervention period, exercise capacity, as measured by the six-minute walk distance, was statistically greater in the intervention group compared to the control group (mean difference (MD) 50.4 m; 95% confidence interval (CI) 15.4–85.2 m). No between-group differences were observed in HRQoL (standardised mean difference (SMD) 0.17; 95% CI −0.16–0.49) or FEV₁ (MD −0.13 L; 95% CI −0.36–0.11 L). Differences in quadriceps force were not demonstrated on completion of the intervention period.

Conclusions

Evidence from our review suggests that exercise training may potentially increase the exercise capacity of people following lung resection for NSCLC. The findings of this review should be interpreted with caution due to disparities between the studies, methodological limitations, some significant risks of bias and small sample sizes.     

Is there a prognostic role of K-ras point mutations in the serum of patients with advanced non-small cell lung cancer?

The purpose of this study was to investigate the prognostic significance of K-ras mutations in circulating DNA in advanced non-small lung cancer (NSCLC) patients. Serum samples were assessed prior to platinum-based chemotherapy start in 67 patients with advanced NSCLC (stage IIIB or IV), treated between April 1999 and June 2002. Patients were not previously treated with chemotherapy. K-ras oncogene mutations at codon 12 were analyzed by genomic amplification and direct sequencing of the patient's DNA present in serum. Pre-treatment serum was available in all 67 patients. Twenty patients (30%) demonstrated K-ras mutations while 47 patients (70%) had wild-type K-ras. Among K-ras mutations, the amino acid glycine was substituted by cystein in 90% and valine in 10%. When patients were grouped according to K-ras genotype, there was no significant difference for any of the baseline patient characteristics. There was a tendency towards a higher response rate for patients with K-ras mutations versus wild-type K-ras in serum, however not statistically significant (p = 0.37). Median progression-free survival was 7.3 months versus 5.5 months in patients with mutations and with wild-type K-ras, respectively (p = 0.23). For median overall survival time, the mutation group was comparable to the wild-type K-ras group with 12.5 and 11.4 months, respectively (p = 0.28). In conclusion, there were no significant differences between the patients with K-ras mutations and those with wild-type genotype with respect to baseline patient characteristics, response rates, progression-free survival, or overall survival.     

Is there a role for surgery in stage Ⅲ A-N2 non-small cell lung cancer?

The role of surgery in stage ⅢA-N2 non-small cell lung cancer(NSCLC) remains controversial.Most important prognostic factors are mediastinal downstaging and complete surgical resection.Different restaging techniques exist to evaluate response after induction therapy and these are subdivided into non-invasive,invasive and alternative or minimally invasive techniques.In contrast to imaging or functional studies,remediastinoscopy provides pathological evidence of response after induction therapy.Although technically more challenging than a first procedure,remediastinoscopy can select patients for subsequent thoracotomy and provides prognostic information.An alternative approach consists of the use of minimally invasive staging procedures as endobronchial or endoscopic esophageal ultrasound to obtain an initial proof of mediastinal nodal involvement.Mediastinoscopy is subsequently performed after induction therapy to evaluate response.In this way,a technically more difficult remediastinoscopy can be avoided.Stage ⅢA-N2 NSCLC represents a heterogenous spectrum of locally advanced disease and different subsets exist.When N2 disease is discovered during thoracotomy after negative,careful preoperative staging a resection should be performed if this can be complete.Postoperative radiotherapy will decrease local recurrence rate but not overall survival.Adjuvant chemotherapy increases survival and is presently recommended in these cases.Most patients with pathologically proven N2 disease detected during preoperative work-up will be treated by induction therapy followed by surgery or radiotherapy.In two large,recently completed,phase Ⅲ trials there was no difference in overall survival between the surgical and radiotherapy arm,but in one trial there was a difference in progression-free survival in favor of the surgical arm.In the surgery arm the rate of local recurrences was also lower in both trials.Surgical resection may be recommended in those patients with proven mediastinal downstaging after induction therapy who can preferentially be treated by lobectomy.Pneumonectomy has a significantly higher mortality and morbidity rate,especially after induction chemoradiotherapy.Patients with bulky N2 disease are mostly treated with combined chemoradiotherapy although the precise treatment scheme has not been determined yet.     

Is there a preferred combination chemotherapy regimen for metastastic non-small cell lung cancer?

Since over 70% of patients with non-small cell lung cancer (NSCLC) have advanced (locally advanced or metastatic) disease, the majority of NSCLC patients might benefit from chemotherapy. During the past decade, a number of new agents (paclitaxel, docetaxel, gemcitabine, vinorelbine, irinotecan, and topotecan) have been found to be effective against lung cancer. These agents have been combined with cisplatin, carboplatin, and nonplatinum drugs to treat NSCLC. They, in general, produce median survival times of 8-10 months and 1- and 2-year survival rates of 35%-40% and 10%-15%, respectively. Based on this review, there is not a preferred combination chemotherapy regimen to treat advanced NSCLC patients. However, there are a number of different regimens from which to choose.     

Evolution of treatment strategies for oligometastatic NSCLC patients – A systematic review of the literature

BackgroundThe concept of oligometastatic disease (OMD) has expanded the scope of potentially curative therapy for metastatic NSCLC. However, large uncertainties remain regarding its definition and optimal management strategies. We therefore conducted a systematic review to investigate the value of various multimodality treatment concepts.MethodsWe searched the available literature in Pubmed, Medline and EMBASE using the terms “oligomet*”, “synchron*”, “oligorec*”, “metachr*” “NSCLC”, “lung cancer” and “stage IV” and included studies reporting treatment regimens and outcomes on radically treated patients with either “synchronous”, “metachronous” or “mixed” OMD. Only de-novo diagnosis of OMD was considered. The impact of patient and treatment characteristics on overall survival (OS) and time trends in patterns of care were investigated.Results54 studies published between 1987 and 2018 were included. Despite a wide range of OMD definitions, 90.1% of patients were treated for a single metastasis. Systemic therapy was used as backbone treatment for most patients. Although surgery was the preferred local treatment in earlier studies, the use of stereotactic radiotherapy increased rapidly after 2011. No OS difference was observed between surgery or radiotherapy as the treatment of primary tumor or metastases, respectively. A time trend towards improved OS after 2011 could be detected.ConclusionsWhile evidence in favor of radical treatment is emerging, most studies remain retrospective and mainly evaluate patients with singular metastases. While surgery, stereotactic radiotherapy and chemotherapy are the cornerstones of current treatment strategies, future clinical trials need to address the high risk of distant metastases by integrating targeted or immunotherapy.     

Targeted therapy in non-small cell lung cancer

Recent progress in molecular biology has enabled us to better understand the molecular mechanism underlying pathogenesis of human malignancy including lung cancer. Sequencing of human genome has identified many oncogenes and tumor suppressor genes, giving us a better understanding of the molecular events leading to the formation, progression, metastasis, and the development of drug resistance in human     

Has Cox-2 a prognostic role in non-small-cell lung cancer? A systematic review of the literature with meta-analysis of the survival results

Cyclooxygenase-2 (COX-2) is overexpressed in lung cancer, especially in adenocarcinoma (ADC). Our aim was to determine the prognostic value of COX-2 on survival in patients with lung cancer. Studies evaluating the survival impact of COX-2 in lung cancer, published until December 2005, were selected. Data for estimation of individual hazard ratios (HR) for survival were extracted from the publications and combined in a pooled HR. Among 14 eligible papers, all dealing with non-small-cell lung cancer, 10 provided results for meta-analysis of survival data (evaluable studies). Cyclooxygenase-2 positivity was associated with reduced survival, improved survival or no statistically significant impact in six, one and seven studies, respectively. Combined HR for the 10 evaluable studies (1236 patients) was 1.39 (95% confidence intervals (CI): 0.97-1.99). In stage I lung cancer (six evaluable studies, 554 patients), it was 1.64 (95% CI: 1.21-2.24). No significant impact was shown in ADC. A slight detrimental effect on survival in patients with lung cancer is associated with COX-2 expression, but the statistical significance is not reached. This effect is statistically significant in stage I, suggesting that COX-2 expression could be useful at early stages to distinguish those with a worse prognosis.     

Is"chemobrain" a transient state? A prospective pilot study among persons with non-small cell lung cancer

In patients with stage III non-small cell lung cancer (NSCLC), chemotherapy combined with radiation therapy modestly improves survival when compared with radiotherapy alone. In light of the small survival benefit,there is a need to quantify any potential loss of neurocognitive function that may result from chemotherapy in this patient population. The current study examines cognitive functioning in 14 stage III NSCLC patients who received treatment with cisplatin/etoposide/radiotherapy. Patients were assessed before receiving chemotherapy and at 1 and 7 months after treatment. At each time point, participants were administered a comprehensive battery of psychological and neuropsychological tests. In all, 71% of patients demonstrated cognitive impairment prior to any treatment. One month post chemotherapy, the majority of patients (62%) experienced cognitive decline; however, these negative effects apparently dissipated by 7 months post treatment, suggesting that the untoward effects of chemotherapy in these specific patients given this chemotherapy regimen may have been transitory. Cognitive decline did not appear to be associated with age, mood, fatigue, or quality-of-life measures. These findings demonstrated the importance of employing both a pre- and extended post-treatment assessment in chemotherapy research.