Adjuvant Therapy For Non-small Cell Lung Cancer Research Articles

Shenqi Fuzheng injection restores the sensitivity to gefitinib in non-small cell lung cancer by inhibiting the IL-22/STAT3/AKT pathway

Context Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Gefitinib is a first-line treatment for NSCLC. However, its effectiveness is hindered by the development of drug resistance. At present, Shenqi Fuzheng injection (SFI) is widely accepted as an adjuvant therapy in NSCLC. Objective This study investigates the molecular mechanism of SFI when combined with gefitinib in regulating cell progression among EGFR-TKI-resistant NSCLC. Materials and methods We established gefitinib-resistant PC9-GR cells by exposing gefitinib escalation from 10 nM with the indicated concentrations of SFI in PC9 cells (1, 4, and 8 mg/mL). Quantitative real-time polymerase chain reaction was performed to assess gene expression. PC9/GR and H1975 cells were treated with 50 ng/mL of interleukin (IL)-22 alone or in combination with 10 mg/mL of SFI. STAT3, p-STAT3, AKT, and p-AKT expression were evaluated using Western blot. The effects on cell proliferation, clonogenicity, and apoptosis in NSCLC cells were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation and flow cytometry assays. Results SFI treatment alleviated the development of gefitinib resistance in NSCLC. PC9/GR and H1975 cells treated with SFI significantly exhibited a reduction in IL-22 protein and mRNA overexpression levels. SFI effectively counteracted the activation of the STAT3/AKT signaling pathway induced by adding exogenous IL-22 to PC9/GR and H1975 cells. Moreover, IL-22 combined with gefitinib markedly increased cell viability while reducing apoptosis. In contrast, combining SFI with gefitinib and the concurrent treatment of SFI with gefitinib and IL-22 demonstrated the opposite effect. Discussion and Conclusion SFI can be a valuable therapeutic option to address gefitinib resistance in NSCLC by suppressing the IL-22/STAT3/AKT pathway.

Impact of travel distance on receipt of indicated adjuvant therapy in resected non–small cell lung cancer

ObjectiveWe have previously demonstrated the negative impact of travel distance on adherence to surveillance imaging guidelines for resected non–small cell lung cancer (NSCLC). The influence of patient residential location on adherence to recommended postoperative treatment plans remains unclear. We sought to characterize the impact of travel distance on receipt of indicated adjuvant therapy in resected NSCLC. MethodsWe performed a single-institution, retrospective review of patients with stage II-III NSCLC who underwent upfront pulmonary resection, 2012-2016. Clinicopathologic and operative/perioperative details of treatment were collected. Travel distance was measured from patients' homes to the operative hospital. Our primary outcome was receipt of adjuvant systemic or radiotherapy. Travel distance was stratified as <100 or >100 miles. Multivariable logistic regression was performed. ResultsIn total, 391 patients met inclusion criteria, with mean age of 65.9 years and fairly even sex distribution (182 women, 49.2%). Most patients were Non-Hispanic White (n = 309, 83.5%), and most frequent clinical stage was II (n = 254, 64.9%). Indicated adjuvant therapy was received by 266 (71.9%), and median distance traveled was 209 miles (interquartile range, 50.7-617). Multivariate analysis revealed that longer travel distance was inversely associated with receipt of indicated adjuvant therapy (odds ratio, 0.13; 95% confidence interval, 0.06-0.26; P < .001). In addition, Black patients were less likely to receive appropriate treatment (odds ratio, 0.05; 95% confidence interval, 0.02-0.15; P < .001). ConclusionsTravel distance >100 miles negatively impacts the likelihood of receiving indicated adjuvant therapy in NSCLC. Indications for systemic therapy in earlier staged disease are rapidly expanding, and these findings bear heightened relevance as we aim to provide equitable access to all patients.

Validation of recurrence prediction using circulating tumor DNA in patients with curatively treated early stage non-small cell lung cancer.

8535 Background: Stage II-III non-small cell lung cancer (NSCLC) patients receive adjuvant chemotherapy after surgery as standard-of-care treatment, despite an absolute 5-year disease free survival benefit of only 5.8%. Stage I patients do not receive adjuvant treatment but may benefit. Identification of residual disease by circulating tumor DNA (ctDNA) after curative intent therapy may allow more accurate decisions. Methods: Tumor tissue and serial plasma samples were collected from stage I-III NSCLC patients enrolled in the LEMA trial (NCT02894853). Somatic mutations identified by tumor exome sequencing were used to design patient-specific RaDaR assays, targeting up to 48 variants per patient, to analyze ctDNA in serial plasma samples. Results were compared and combined with an independent dataset (LUCID; Gale et al, Annals Oncol 2022). Results: In LEMA, 129 patients (53% stage I, 18% stage II and 29% stage III) were treated with curative intent by surgery (n=117), chemoradiation (n=8) or stereotactic radiotherapy (n=4) and followed for a median of 3.4 years. The LUCID dataset included 88 patients (49%/28%/23% in stage I/II/III). Results in the two cohorts were highly concordant (Table) and were assessed in the combined dataset of 808 serial plasma samples. Before treatment, ctDNA was detected in 22%, 72% and 90% of patients with stage I, II and III disease. ctDNA was detected post-treatment (at least one positive samples ≥14 days after the end of therapy) in 41/65 (63%) of patients who developed radiographic recurrence of their primary cancer, and preceded recurrence by a median of 204 days. For recurrence prediction by ctDNA detection post-treatment, the sensitivity, specificity, positive and negative predictive value (PPV and NPV) in stage I patients were 53%, 99%, 91% and 90%. In stage II-III patients, sensitivity was higher but specificity and NPV were lower (67%, 93%, 91% and 74%, respectively). ctDNA detection after treatment was associated with shorter recurrence-free survival (hazard ratio (HR) 11.5, P=1.8x10-32) and overall survival (HR 8.1, P=1.2x10-17). Conclusions: ctDNA detection by RaDaR assays predicted recurrence in two independent cohorts, confirming the potential to identify patients for adjuvant treatment. In stage I patients with positive ctDNA, adjuvant treatment could be offered with confidence due to high specificity of 99% and PPV of 91%. In stage II-III patients, the primary cancer recurred in a quarter of patients with no ctDNA detected post-treatment (NPV 74%). Our results help identify the potential role for ctDNA analysis as a decision support tool for adjuvant therapy in NSCLC. [Table: see text]

The Efficacy and Hemorheological Indexes of Ginseng and Its Active Components for Patients with Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Non-small cell lung cancer (NSCLC) is still a slightly less orphan disease after immunotherapy, and routine treatment has low efficiency and adverse events. Ginseng is commonly used in the treatment of NSCLC. The purpose of this study is to assess the efficacy and hemorheological indexes of ginseng and its active components in patients with non-small cell lung cancer. A comprehensive literature search was performed in PubMed, the Cochrane Library, Medline (Ovid), the Web of Science, Embase, CKNI, Wan Fang, VIP, and SinoMed up to July 2021. Only randomized controlled trials evaluating ginseng in combination with chemotherapy versus chemotherapy alone in NSCLC patients were included. Primary outcomes included patients' condition after using ginseng or its active components. Secondary outcomes included changes in immune cells, cytokines, and secretions in serum. Data were extracted by two independent individuals, and the Cochrane Risk of Bias tool version 2.0 was applied for the included studies. Systematic review and meta-analysis were performed by RevMan 5.3 software. The results included 1480 cases in 17 studies. The results of the integration of clinical outcomes showed that the treatment of ginseng (or combination of ginseng with chemotherapy) can improve the quality of life for patients with NSCLC. Analysis of immune cell subtypes revealed that ginseng and its active ingredients can upregulate the percentages of antitumor immunocyte subtypes and downregulate the accounts of immunosuppressive cells. In addition, a reduction of the inflammatory level and an increase of antitumor indicators in serum were reported. Meta-analysis showed that Karnofsky score: WMD = 16, 95% CI (9.52, 22.47); quality-of-life score: WMD = 8.55, 95%CI (6.08, 11.03); lesion diameter: WMD = -0.45, 95% CI (-0.75, -0.15); weight: WMD = 4.49, 95% CI (1.18, 7.80); CD3+: WMD = 8.46, 95% CI (5.71, 11.20); CD4+: WMD = 8.45, 95% CI (6.32, 10.57)+; CD8+: WMD = -3.76, 95% CI (-6.34, -1.18); CD4+/CD8+: WMD = 0.32, 95% CI (0.10, 0.53); MDSC: WMD = -2.88, 95% CI (-4.59, -1.17); NK: WMD = 3.67, 95% CI (2.63, 4.71); Treg: WMD = -1.42, 95% CI (-2.33, -0.51); CEA: WMD = -4.01, 95% CI (-4.12, -3.90); NSE: WMD = -4.00, 95% CI (-4.14, -3.86); IL-2: WMD = 9.45, 95% CI (8.08, 10.82); IL-4: WMD = -9.61, 95% CI (-11.16, -8.06); IL-5: WMD = -11.95, 95% CI (-13.51, -10.39); IL-6: WMD = -7.65, 95% CI (-8.70, -6.60); IL-2/IL-5: WMD = 0.51, 95% CI (0.47, 0.55); IFN-γ: WMD = 15.19, 95% CI (3.16, 27.23); IFN-γ/IL-4: WMD = 0.91, 95% CI (0.85, 0.97); VEGF: WMD = -59.29, 95% CI (-72.99, -45.58); TGF-α: WMD = -10.09, 95% CI (-12.24, -7.94); TGF-β: WMD = -135.62, 95% CI (-147.00, -124.24); TGF-β1: WMD = -4.22, 95% CI (-5.04, -3.41); arginase: WMD = -1.81, 95% CI (-3.57, -0.05); IgG: WMD = 1.62, 95% CI (0.18, 3.06); IgM: WMD = -0.45, 95% CI (-0.59, -0.31). All results are statistically significant. No adverse events were reported in the included articles. It is a reasonable choice to use ginseng and its active components as adjuvant therapy for NSCLC. Ginseng is helpful for NSCLC patients' conditions, immune cells, cytokines, and secretions in the serum.

The Pharmacological Mechanism of Curcumin against Drug Resistance in Non-Small Cell Lung Cancer: Findings of Network Pharmacology and Bioinformatics Analysis.

The pharmacological mechanism of curcumin against drug resistance in non-small cell lung cancer (NSCLC) remains unclear. This study aims to summarize the genes and pathways associated with curcumin action as an adjuvant therapy in NSCLC using network pharmacology, drug-likeness, pharmacokinetics, functional enrichment, protein-protein interaction (PPI) analysis, and molecular docking. Prognostic genes were identified from the curcumin-NSCLC intersection gene set for the following drug sensitivity analysis. Immunotherapy, chemotherapy, and targeted therapy sensitivity analyses were performed using external cohorts (GSE126044 and IMvigor210) and the CellMiner database. 94 curcumin-lung adenocarcinoma (LUAD) hub targets and 41 curcumin-lung squamous cell carcinoma (LUSC) hub targets were identified as prognostic genes. The anticancer effect of curcumin was observed in KEGG pathways involved with lung cancer, cancer therapy, and other cancers. Among the prognostic curcumin-NSCLC intersection genes, 20 LUAD and 8 LUSC genes were correlated with immunotherapy sensitivity in the GSE126044 NSCLC cohort; 30 LUAD and 13 LUSC genes were associated with immunotherapy sensitivity in the IMvigor210 cohort; and 12 LUAD and 13 LUSC genes were related to chemosensitivity in the CellMiner database. Moreover, 3 LUAD and 5 LUSC genes were involved in the response to targeted therapy in the CellMiner database. Curcumin regulates drug sensitivity in NSCLC by interacting with cell cycle, NF-kappa B, MAPK, Th17 cell differentiation signaling pathways, etc. Curcumin in combination with immunotherapy, chemotherapy, or targeted drugs has the potential to be effective for drug-resistant NSCLC. The findings of our study reveal the relevant key signaling pathways and targets of curcumin as an adjuvant therapy in the treatment of NSCLC, thus providing pharmacological evidence for further experimental research.

Advances in metformin‑based metabolic therapy for non‑small cell lung cancer (Review).

Therapeutic approaches that target the metabolism of tumor cells have been a popular research topic in recent years. Previous studies have demonstrated that glycolysis inhibitors reduce the proliferation of non-small cell lung cancer (NSCLC) cells by interfering with the aerobic glycolytic pathway. However, the mitochondrial oxidative phosphorylation (OXPHOS) pathway in tumor cells has also been implicated in lung cancer metabolism. Metformin, a known inhibitor of mitochondrial OXPHOS, has been indicated to reduce NSCLC morbidity and mortality in clinical studies. The present article reviewed the therapeutic effects of metformin against NSCLC, both as a single agent and combined with other anticancer treatments, in order to provide a theoretical basis for its clinical use in adjuvant therapy for NSCLC.

Immunotherapy and Vaccination in Surgically Resectable Non-Small Cell Lung Cancer (NSCLC).

Early-stage NSCLC (stages I and II, and some IIIA diseases) accounts for approximately 30% of non-small cell lung cancer (NSCLC) cases, with surgery being its main treatment modality. The risk of disease recurrence and cancer-related death, however, remains high among NSCLC patients after complete surgical resection. In previous studies on the long-term follow-up of post-operative NSCLC, the results showed that the five-year survival rate was about 65% for stage IB and about 35% for stage IIIA diseases. Platinum-based chemotherapy with or without radiation therapy has been used as a neoadjuvant therapy or post-operative adjuvant therapy in NSCLC, but the improvement of survival is limited. Immune checkpoint inhibitors (ICIs) have effectively improved the 5-year survival of advanced NSCLC patients. Cancer vaccination has also been explored and used in the prevention of cancer or reducing disease recurrence in resected NSCLC. Here, we review studies that have focused on the use of immunotherapies (i.e., ICIs and vaccination) in surgically resectable NSCLC. We present the results of completed clinical trials that have used ICIs as neoadjuvant therapies in pre-operative NSCLC. Ongoing clinical trials investigating ICIs as neoadjuvant and adjuvant therapies are also summarized.

A study on the mechanism of bruceine D in the treatment of non-small cell lung cancer H1299 cells

Background: Non-small cell lung cancer (NSCLC) is considered one of the leading causes of cancer-related death. Despite the availability of drugs for the treatment of NSCLC, the need for the development of novel agents with high efficiency and fewer adverse effects remains unmet. The natural compound bruceine D (BD) is widely recognized for its notable anti-inflammatory, antiparasitic, and hypoglycemic activities. However, it is unclear whether BD can be used as a novel agent for NSCLC treatment. Materials and Methods: MTT and colony formation assays were used to assess the antiproliferative effect of BD on NSCLC cells. Wound healing and transwell assays were performed to determine the effect of BD on the migration and invasion of H1299 cells, respectively. Western blotting assay was used to detect the expression levels of proteins. Results: We demonstrated that BD significantly inhibited the proliferation of H1299, A549, and H226 cells with respective IC50 values of 6.06 ± 0.52, 7.15 ± 0.90, and 7.21 ± 0.75 μM. In addition, BD suppressed colony formation of H1299 cells in a dose-dependent manner. Following treatment with BD, the migration and invasive capabilities of H1299 cells were significantly inhibited in a dose- and time-dependent manner. Moreover, the results of Western blotting demonstrated that BD treatment resulted in the upregulation of the protein expression of E-cadherin and downregulation of the expression of N-cadherin, twist, snail, integrin αv, integrin β4, matrix metalloproteinase-7, and β-catenin proteins. Conclusion: BD inhibits proliferation, migration, and invasion of NSCLC cells; therefore, BD may be considered for its potential in adjuvant therapy for NSCLC.

Mifepristone inhibits non-small cell lung carcinoma cellular escape from DNA damaging cisplatin

BackgroundLung cancer is the leading cause of cancer deaths in the world. The major histopathological subtype of lung cancer is non-small cell lung cancer (NSCLC). Platinum-based therapy is the standard of care for patients with advanced stage NSCLC. However, even with treatment, most patients will die of this disease within 5 years and most of these deaths are due to recurrence. One strategy to inhibit recurrence is to use cytostatic compounds following courses of lethal chemotherapy. We have shown in various cancer cell types that mifepristone (MF), an anti-progestin/anti-glucocorticoid, is a powerful cytostatic anti-cancer agent. Thus, in this work we tested the hypothesis that MF should be efficacious in inducing cytostasis and preventing repopulation of NSCLC following cisplatin (CDDP) therapy.MethodsWe established an in vitro approach wherein human NSCLC cells with different genetic backgrounds and sensitivities to CDDP (A549 and H23) were exposed to rounds of lethal concentrations of CDDP for 1 h followed or not by MF monotherapy. Every 2 days, cell number, cell viability, and colony-forming ability of viable cells were studied.ResultsCDDP killed the majority of cells, yet there were remnant cells escaping CDDP lethality and repopulating the culture, as evidenced by the improved clonogenic survival of viable cells. In contrast, when cells exposed to CDDP where further treated with MF following CDDP removal, their number and clonogenic capacity were reduced drastically.ConclusionThis study reports that there is repopulation of NSCLC cells following a lethal concentration of CDDP monotherapy, that NSCLC cells are sensitive to the growth inhibition properties of MF, and that MF abrogates the repopulation of NSCLC cells following CDDP therapy. Our study supports further evaluating MF as an adjuvant therapy for NSCLC.

Vinorelbine-induced phlebitis is common in patients receiving adjuvant chemotherapy for non-small cell lung cancer (NSCLC).

e20016Background: The combination of vinorelbine and cisplatin is a highly established and widely used regimen as a standard of care for adjuvant therapy for NSCLC, as demonstrated in the JBR.10 an...

Chrysin Increases the Therapeutic Efficacy of Docetaxel and Mitigates Docetaxel-Induced Edema.

Docetaxel (DTX) is an effective commercial anticancer agent for chemotherapy in non–small cell lung cancer (NSCLC), breast cancer, gastric cancer, and prostate cancer, but its adverse effects including edema, neurotoxicity, and hair loss limit its application. To improve the chemotherapeutic efficacy of DTX and reduce adverse effects, combination therapy is one of the alternative methods. So chrysin, which has various biological activities including anticancer effects, was considered. In vitro, the combination of chrysin and DTX was investigated in A549 cells. Increased cytotoxicity, suppressed cellular proliferation, and induced apoptosis were observed with posttreatment of chrysin following DTX treatment. In vivo, chrysin enhanced the tumor growth delay of DTX and increased DTX-induced apoptosis in the A549-derived xenograft model. Furthermore, chrysin prevented DTX-induced edema in ICR mouse. These results indicated that chrysin strengthened the therapeutic efficacy of DTX and diminished the adverse effect of DTX, suggesting chrysin could be exploited as an adjuvant therapy for NSCLC.

Blocking M2 muscarinic receptor signaling inhibits tumor growth and reverses epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC)

Lung cancers express non-neuronal, cholinergic autoparacrine loop, which facilitates tumor growth. Interruption of M3 muscarinic cholinergic signaling has been reported to inhibit small cell lung cancer (SCLC) growth. The purpose of this study is to investigate if blocking autoparacrine muscarinic cholinergic signaling could inhibit non-small cell lung cancer (NSCLC) growth and possible underlying mechanisms. Our results showed that PC9 and A549 cells expressed all 5 subtypes of muscarinic receptor (mAChR) and blocking M2 mAChR (M2R) signaling using selective antagonist methoctramine or short hairpin RNA (shRNA) inhibited tumor cell proliferation in vitro and in vivo. Consistent with AChR agonists stimulating p44/42 MAPK (Erk1/2) and Akt phosphorylation, blocking M2R signaling decreased MAPK and Akt phosphorylation, indicating that non-neuronal ACh functions as an autoparacrine growth factor signaling in part through activation of M2R and downstream MAPK and Akt pathways. Importantly, further studies revealed that blocking M2R signaling also reversed epithelial-mesenchymal transition (EMT) in vitro and in vivo, indicating that non-neuronal ACh promotes EMT partially through activation of M2R. These findings demonstrate that M2R plays a role in the growth and progression of NSCLC and suggest M2R antagonists may be an efficacious adjuvant therapy for NSCLC.

Remarkable Progress Made in Systemic Therapy of NSCLC

During the past 50 years, substantial progress has been made in the treatment of the most common type of lung cancer, non—small cell lung cancer (NSCLC). This article discusses adjuvant therapy in NSCLC, the treatment of locally advanced stage III NSCLC, as well as progress in the treatment of advanced NSCLC.

Contemporary Trends of the Adjutant Chemotherapy in Non- small Cell Lung Cancer

Adjuvant chemotherapy became a standard of treatment in completely resected non-small cell lung cancer (NSCLC) based on results of big trials meta-analyses, which proved its influence on the decrease of relative mortality risk and absolute improvement of survival. Adjuvant chemotherapy is routinely used according to tumor stage evaluation, performance status (PS) and age of the patients. It is indicated in stage II and IIIA of NSCLC- in frame of clinical studies also in stage IB, in PS 0-1 and in patients under 75 years. Therapy with cisplatin and vinorelbine is a preferred regimen, as well as other drugs, such as paclitaxel, docetaxel, gemcitabine and pemetrexed. The problem is a relatively small dose intensity applied, due to toxic side effects. The present work is evaluating contemporary trends of adjuvant therapy in NSCLC according to latest clinical studies, which are finished or running. Efforts are directed to the improvement of treatment effectiveness, decrease of side effects and refinement of patients selection. Potential treatment benefit of better tolerable carboplatin is verified and results of trials with biologically targeted therapy are expected. Large clinical studies are evaluating the effect of tyrosine kinase inhibitors and angiogenesis inhibitors used either in various combinations with chemotherapy or as monotherapy. Application of vaccines is tested. Contemporary trend of adjuvant therapy is leading to the appropriate patient selection with regard to analysis of several prognostic and predictive biomarkers; it is proposed that future adjuvant therapy will be more and more personalized.

Nanotechnology in Thoracic Surgery

Nanotechnology is an exciting and rapidly progressing field offering potential solutions to multiple challenges in the diagnosis and treatment of lung cancer, with the potential for improving imaging and mapping techniques, drug delivery, and ablative therapy. With promising preclinical results in many applications directly applicable to thoracic oncology, it is possible that the frontiers of minimally invasive thoracic surgery will eventually be explored at the nanoscale.

Referral Patterns for Adjuvant Chemotherapy in Patients with Completely Resected Non-small Cell Lung Cancer

Lung cancer remains a leading cause of cancer-related mortality in North America. Despite potentially curative resection, non-small cell lung cancer (NSCLC) patients remain at high risk of relapse and death, with a 5-year survival rate of less than 67%. Several randomized trials now confirm a survival benefit with adjuvant platinum-based chemotherapy seen in the NSCLC Collaborative Group meta-analysis, including the International Adjuvant Lung Trial, National Cancer Institute of Canada BR.10, and Adjuvant Navelbine International Trialist Association (ANITA) trials, with absolute improvements in 4- and 5-year survival rates of 4% to 15%. This study examines whether referral patterns for adjuvant therapy in NSCLC have changed since the presentation of confirmatory trials. Retrospective chart review was undertaken at a major tertiary care center, identifying patients with completely resected stages I-IIIA NSCLC from May 2003 to May 2005. A total of 204 patients were identified (59 IA, 77 IB, 8 IIA, 41 IIB, and 19 IIIA). Institutional policy before May of 2003 was not to administer adjuvant therapy outside a clinical trial. After presentation of the International Adjuvant Lung Trial in May 2003, 31% (36/115) of patients with completely resected NSCLC from May 2003 to May 2004 were referred for adjuvant chemotherapy. After presentation of the BR.10 and Cancer and Leukemia Group B 9633 results in June 2004, 63% (56/89) were referred between June 2004 and May 2005. Reasons for not referring to a medical oncologist included stage IA disease, surgeon thought adjuvant therapy inappropriate, patient declined, comorbidities, postoperative complications, and advanced age. Of 92 patients referred to medical oncology, 42 (46%) received adjuvant chemotherapy. Reasons for not prescribing adjuvant chemotherapy included patient refusal (50%), comorbidities (14%), stage IA (10%), and advanced age (4%). Vinorelbine/cisplatin was the regimen most commonly used (67%). The presentation of positive adjuvant therapy trials in NSCLC has changed clinical practice substantially, doubling the number of patients with completely resected NSCLC referred for adjuvant chemotherapy since May 2004 (31% versus 63%). Although new evidence to support adjuvant chemotherapy in lung cancer is being disseminated to and accepted by physicians, more patient education and decision support may be required to increase uptake of adjuvant therapy in the early stage NSCLC population.

Differences in primary care clinicians’ approach to non-small cell lung cancer (NSCLC) patients compared to breast cancer (BrCa)

7041 Background: Lung cancer is a disease associated with a stigma of being primarily self-induced via smoking and therefore avoidable. It is unclear if this stigma results in feelings of guilt and shame on the part of the patient, and a difference in care on the part of primary care physicians (MDs), both of which could lead to differences in treatment and patient self-advocacy, and ultimately poorer outcomes. Methods: We conducted a prospective survey study of 1,132 MDs who were randomized into 4 groups. Each group received a questionnaire representing a clinical scenario (smoker/NSCLC; nonsmoker/NSCLC; smoker/BrCa; nonsmoker/BrCa). The scenarios were identical in terms of stage, gender and outcome; but varied in the disease and smoking history (smoker (S) vs. nonsmoker (NS)). The primary objective was to collect preliminary data to determine if these MDs approached the care and referral of patients (pts) with NSCLC or BrCa differently. A secondary objective was to determine whether or not tobacco use influenced the MD’s approach to the cancer pts. Comparisons of response patterns between the groups were evaluated by Chi-square analysis. Results: 672 questionnaires were completed: 175 in the NS/BrCa, 177 in the S/BrCa, 166 in the NS/NSCLC and 154 in the S/NSCLC scenarios. We observed that MDs were less likely to refer pts with advanced NSCLC to an oncologist than BrCa pts (p=&lt;0.001). More MDs knew that chemotherapy improved survival in pts with advanced BrCa than did MDs regarding chemotherapy use in advanced NSCLC (p=0.0145). In addition, more MDs stated they did not know the benefit of adjuvant therapy for NSCLC than for BrCa (p= &lt;0.001). As a result, more pts with advanced BrCa were referred for further therapy vs. NSCLC pts, who were more likely to be referred only for symptom control (p=0.0092). BrCa pts also had more aggressive follow up than did pts with NSCLC (p=0.0256). There was no statistical significant difference when comparing smoking vs. non-smoking pts. Conclusions: We conclude that there is a significant lack of knowledge in the primary care physician regarding the treatment of pts with advanced stage NSCLC, and the role and benefit of adjuvant therapy. This might lead to a less aggressive referral pattern in these pts to clinical oncologists. [Table: see text]

Adjuvant and Neoadjuvant Therapy for Early-Stage Non–Small-Cell Lung Cancer

Early-stage non-small-cell lung cancer (NSCLC) carries with it an unfavorable prognosis even in patients who have undergone surgical intervention. Efforts to improve the outcome of patients with early-stage NSCLC have focused on adjuvant or neoadjuvant chemotherapy. The role of adjuvant therapy in NSCLC has been clarified by the recent publication of several large randomized trials. The International Adjuvant Lung Trial was the first prospective trial to report that adjuvant chemotherapy following complete surgical resection of NSCLC improved absolute overall survival by approximately 5% at 5 years. This result has subsequently been confirmed by several other trials. As a result, adjuvant chemotherapy following complete resection of stage IB-III NSCLC can now be considered the standard of care. Neoadjuvant chemotherapy, which has long been investigated for stage III NSCLC, was also recently explored in stage I/II NSCLC. Although neoadjuvant chemotherapy seems promising, more work is needed to comprehensively evaluate and optimize this approach. The current evidence for adjuvant and neoadjuvant therapy in early-stage NSCLC is reviewed in this article.

Adjuvant treatment of lung cancer: Current status and potential applications of new regimens

Non-small-cell lung cancer (NSCLC) accounts for approximately 80% of lung cancers diagnosed worldwide. Surgical resection offers the best chance for cure for those patients diagnosed with early-stage disease; however, the vast majority of patients will eventually relapse. Despite complete surgical resection, recurrences are likely due to undetectable microscopic disease at diagnosis, making these patients potential candidates for effective adjuvant therapy. Postoperative radiation therapy may actually have a detrimental effect in patients with NO-N1 disease and has been shown to possibly prevent local recurrences in patients with N2 disease. Although results from a large meta-analysis of data on adjuvant chemotherapy suggested an absolute benefit of 5% at 5 years from cisplatin-based chemotherapy, a rate similar to that seen in breast and colon cancers where adjuvant chemotherapy is a standard of care, the use of adjuvant therapy in NSCLC remained controversial. In addition, results of the International Adjuvant Lung Cancer Trial (IALT), which compared adjuvant cisplatin-based chemotherapy to observation in patients with resected stage-I-IIIA NSCLC, suggested that adjuvant therapy had the potential to prevent a substantial number of deaths each year. Two recently reported landmark studies have demonstrated the survival advantages of adjuvant therapy for patients with early-stage NSCLC. Docetaxel, one of the most active agents for advanced NSCLC, is also regularly used for locally advanced disease as part of neoadjuvant or combined-modality regimens. As recent findings have established the value of adjuvant chemotherapy for early-stage NSCLC, agents such as docetaxel warrant rigorous evaluation in this setting.