Adjuvant Treatment Of Lung Cancer Research Articles

PP01.108 Trial in Progress: Shared Decision-Making Encounter Tool for Adjuvant Treatment of Lung Cancer: Randomized Control Trial

PP01.108 Trial in Progress: Shared Decision-Making Encounter Tool for Adjuvant Treatment of Lung Cancer: Randomized Control Trial

Molecular mechanism of ion channel protein TMEM16A regulated by natural product of narirutin for lung cancer adjuvant treatment

Cancer chemotherapy drugs are widely criticized for their serious side effects and low cure rate. Therefore, adjuvant therapy as a combination with chemotherapy administration is being accepted by many patients. However, unclear drug targets and mechanisms limit the application of adjuvant treatment. In this study, we confirmed TMEM16A is a key drug target for lung adenocarcinoma, and narirutin is an effective anti-lung adenocarcinoma natural product. Virtual screening and fluorescence experiments confirmed that narirutin inhibits the molecular target TMEM16A, which is specific high-expression in lung adenocarcinoma. Molecular dynamics simulations and electrophysiological experiments revealed the precise molecular mechanism of narirutin regulating TMEM16A. The anticancer effect of narirutin and its synergistic effect on cisplatin were explored by cell proliferation, migration, and apoptosis assays. The signaling pathways regulated by narirutin were analyzed by western blot. Tumor xenograft mice experiments demonstrated the synergistic anticancer effect of narirutin and cisplatin, and the side effects of high concentrations of cisplatin were almost eliminated. Pharmacokinetic experiments showed the biological safety of narirutin is satisfactory in vivo. Based on the significant anticancer effect and high biosafety, naringin has great potential as a functional food in the adjuvant treatment of lung cancer.

Efficacy of ω-3 Polyunsaturated Fatty Acids in Patients with Lung Cancer Undergoing Radiotherapy and Chemotherapy: A Meta-Analysis.

Background Radiotherapy and chemotherapy in patients with lung cancer can lead to a series of problems such as malnutrition and inflammatory reaction. Some studies have shown that ω-3 polyunsaturated fatty acids (PUFAs) could improve malnutrition and regulate inflammatory reaction in these patients, but no relevant meta-analysis exists. Methods We systematically searched randomized controlled trials of ω-3 PUFAs in the adjuvant treatment of lung cancer in the PubMed, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), and Wanfang databases. Relevant outcomes were extracted, and we pooled standardized mean differences (SMDs) using a random or fixed-effects model. The risk of bias was evaluated according to the Cochrane Handbook (version 15.1). The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results A total of 7 studies were included. The SMDs (95% CI) of body weight change, albumin change, energy intake, and protein intake at the end of intervention were 1.15 (0.50, 1.80), 0.60 (0.11, 1.09), 0.39 (−0.10, 0.89), and 0.27 (−0.04, 0.58), respectively. The SMDs (95% CI) of CRP change and TNF-α change were −3.44 (−6.15, −0.73) and −1.63 (−2.53, −0.73), respectively. Conclusions ω-3 PUFAs can improve nutritional status and regulate indicators of inflammation in patients with lung cancer undergoing radiotherapy and chemotherapy. This study was registered in the PROSPERO (registration number: CRD42022307699).

The repression and reciprocal interaction of DNA methyltransferase 1 and specificity protein 1 contributes to the inhibition of MET expression by the combination of Chinese herbal medicine FZKA decoction and erlotinib

Ethnopharmacological relevanceThe Chinese herbal medicine Fuzheng Kang-Ai (FZKA) decoction obtained from Guangdong Kangmei Pharmaceutical Company, which contains 12 components with different types of constituents, has been used as part of the adjuvant treatment of lung cancer for decades. We previously showed that FZKA decoction enhances the growth inhibition of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-resistant non-small cell lung cancer (NSCLC) cells by suppressing glycoprotein mucin 1 (MUC1) expression. However, the molecular mechanism underlying the therapeutic potential, particularly in sensitizing or/and enhancing the anti-lung cancer effect of EGFR-TKIs, remains unclear. Materials and methodsCell viability was measured using 3-(4, 5-diMEThylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and 5-ethynyl -2′-deoxyuridine (EdU) assays. Western blot analysis was performed to examine the protein expressions of DNA methyltransferase 1 (DNMT1), specificity protein 1 (SP1), and MET, an oncogene encoding for a trans-membrane tyrosine kinase receptor activated by the hepatocyte growth factor (HGF). The expression of MET mRNA was measured by quantitative real-time PCR (qRT-PCR). Exogenous expression of DNMT1 and SP1, and MET were carried out by transient transfection assays. The promoter activity of MET was tested using Dual-luciferase reporter assays. A nude mouse xenografted tumor model further evaluated the effect of the combination of FZKA decoction and erlotinib in vivo. ResultsThe combination of FZKA and erlotinib produced an even greater inhibition of NSCLC cell growth. FZKA decreased the expressions of DNMT1, SP1, and MET (c-MET) proteins, and the combination of FZKA and erlotinib demonstrated enhanced responses. Interestingly, there was a mutual regulation of DNMT1 and SP1. In addition, exogenously expressed DNMT1 and SP1 blocked the FZKA-inhibited c-MET expression. Moreover, excessive expressed MET neutralized FZKA-inhibited growth of NSCLC cells. FZKA decreased the mRNA and promoter activity of c-MET, which was not observed in cells with ectopic expressed DNMT1 gene. Similar findings were observed in vivo. ConclusionFZKA decreases MET gene expression through the repression and mutual regulation of DNMT1 and SP1 in vitro and in vivo. This leads to inhibit the growth of human lung cancer cells. The combination of FZKA and EGFR-TKI erlotinib exhibits synergy in this process. The regulatory loops among the DNMT1, SP1 and MET converge in the overall effects of FZKA and EGFR-TKI erlotinib. This in vitro and in vivo study clarifies an additional novel molecular mechanism underlying the anti-lung cancer effects in response to the combination of FZKA and erlotinib in gefitinib-resistant NSCLC cells.

ShenQi FuZheng Injection ameliorates fatigue-like behavior in mouse models of cancer-related fatigue

Cancer-related fatigue (CRF) not only has a negative impact on work, daily activities and social relationships, but also be a predictor of cancer patients' survival. And it has no FDA-approved therapy. ShenQi FuZheng Injection (SFI) is clinically used for adjuvant treatment of lung cancer and gastric cancer. And we found that SFI can improve the incidence of CRF in patients with gastric cancer. However, its efficacy against CRF remains to be elucidated. In the present study we established a tumor-bearing mouse fatigue model, conducted the forced swim test (FST) and grip strength measurements to evaluate the therapeutic effect of SFI. Additionally, we detected inflammation and immune indicators. The result showed that SFI administration could reduce depressive-like behaviors in tumor-bearing mice and inhibit tumor growth. In addition, SFI might improve fatigue symptoms by inhibiting pro-inflammatory cytokines produced by peripheral immune cells, restrain the dysfunction of exhausted T cells and improve the anti-tumor immunity through the targets of PDL1, TIM3 and FOXP3. These data suggested that SFI might be useful in alleviating CRF and provide further support to confirm SFI as a potential therapy for CRF in humans.

The superstars of precision medicine-EGFR inhibitors in adjuvant treatment of lung cancer.

We would like to thank the author of the editorial entitled “EGFR inhibitors in adjuvant treatment of lung cancer—the more specific, the better?” (1) for their interest and comments on our article “Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II–IIIA (N1–N2) EGFR-mutant NSCLC (ADJUVANT/CTONG1104): a randomised, open-label, phase 3 study” (2).

Navigating the Challenges of Adjuvant Chemotherapy in Older Patients with Early-Stage Non-Small-Cell Lung Cancer.

Lung cancer is a disease of older adults. In the US and worldwide, more than 60% of patients being diagnosed are over the age of 65 years. The preferred treatment of stage I-II non-small-cell lung cancer (NSCLC) is surgical resection. Adjuvant chemotherapy with a platinum-based combination is the standard of care for patients with early-stage NSCLC after surgery. However, there have been no large prospective studies to test the efficacy of adjuvant chemotherapy in the elderly, the population most affected by lung cancer. The available evidence is limited to retrospective reviews of large population databases or post hoc analyses of prospective studies in age-unselected populations. This review aims to address the knowledge gap pertaining to the use of adjuvant chemotherapy in older patients with resected NSCLC. There are many barriers to use of adjuvant chemotherapy in older adults with NSCLC. The utilization of adjuvant chemotherapy amongst older adults has been slow but is improving. While the elderly may tolerate a lower dose intensity of chemotherapy compared with younger patients, they do garner benefit from adjuvant chemotherapy. There is a lack of a standardized tool to risk-stratify older patients for adjuvant chemotherapy after resection. Geriatric assessment may help guide decision making in the clinical practice setting. The principles of geriatric assessment and commonly employed tools for such assessment will be reviewed. Further, the emerging therapies in adjuvant treatment of lung cancer based on genetic mutations will be discussed.

EGFR-TKIs in adjuvant treatment of lung cancer: to give or not to give?

Epidermal growth factor receptor-tyrosine-kinase inhibitors (EGFR-TKIs) brought a significant revolution in the treatment of non-small-cell lung cancer (NSCLC). In a short period of time, EGFR-TKIs became the standard of treatment for mutation-positive, advanced stage non-squamous NSCLC. In recent years, second- and third-generation EGFR-TKIs are emerging, further widening the clinical use. However, the question of EGFR-TKIs efficiency in the treatment of early stage NSCLC still remains open. Early clinical trials failed to approve the use of EGFR-TKIs in adjuvant setting. The majority of these early trials were performed in unselected NSCLC populations and without standardized biomarker identification. One should certainly not rely solely on these results and dismiss the use of EGFR-TKIs as adjuvant therapy. Many important questions are still unanswered. Most important issues such as stage heterogeneity (IA–IIIA), timing (after or concomitantly with chemotherapy), and type of administration (monotherapy or combination) need to be answered in near future. Adjuvant TKIs in the treatment of lung cancer might offer significant number of advancements. Having in mind the significant duration of response observed in advance disease setting, there could be place for prolongation of response in adjuvant setting potentially, leading to improvement in survival. TKIs could offer less-toxic adjuvant treatment with better efficiency than chemotherapy. However, there is a chronic lack of randomized controlled trials in this field, leading to inability to draw any scientifically sound conclusion with regard to the adjuvant treatment. For now, the use of EGFR-TKIs outside clinical trial setting is not recommended. The purpose of this review is to evaluate current and available data.

The preliminary results of the application of adjuvant chemoimmunotherapy (АCIТ) in the treatment of patients (pts.) with adenocarcinoma (AC) of the lung.

e18531 Background: Chemotherapy is the standard adjuvant treatment of lung cancer, but it's somewhat ineffective and controversial at the 1 stage of the disease. The authors have developed an origi...

Risk factors for occult nodal metastasis in clinical T1N0 lung cancer: a negative impact on survival

The application of CT imaging has increased the identification of patients with clinical T1N0 (cT1N0) lung cancer. The optimal management strategy for these early stage lung cancers remains unclear. We analyzed the impact of occult nodal metastasis on cT1N0 lung cancer patients. We studied patients with cT1N0 lung cancer enrolled in our database from January 1995 to December 2002. Preoperative staging was confirmed by review of CT and PET scan studies. Pathology specimens were reviewed. Multivariate analysis was performed to determine the risk of occult nodal involvement. Kaplan-Meier method was applied to analyze survival. Two hundred and ninety-seven patients with cT1N0 disease were identified. Fifty-eight percent of patients were pathological T1N0. Overall, 15% of patients had occult nodal metastasis. Logistic regression analysis demonstrated a three-fold increase in the risk of having pathologic stage II or stage III disease with every 1.0 cm increase in tumor size (odds ratio 3.2; 95% CI: 2.3-4.6). Multivariate analysis demonstrated tumor size to be a significant predictor of nodal metastasis (adjusted odds ratio 3.5; 95% CI: 2.4-5.1). Median survival was different between pathological stage I (96.3 months), stage II (41.4 months), and stage III (36.1 months) disease (p=0.002). Clinical T1N0 tumors are often understaged. The risk of occult nodal disease increases with tumor size, and this occult disease negatively impacts survival. Because of the limitations of clinical staging, we believe that lobectomy and lymph node analysis should be offered to cT1N0 lung cancer patients to provide accurate staging and to optimize multimodality adjuvant treatment of lung cancer.

Poly TLR agonist polyantigenic vaccine (Mycobacterium w) in palliative therapy of head and neck cancer

12512 Background: Poly TLR poly-antigenic vaccine containing Mycobacterium w (Mw) is found useful in the management of lung cancer and bladder cancer when used along with standard therapy1,2 but not in Head and Neck cancer3–4. This study was carried out to evaluate its efficacy as a single agent in advanced head & neck cancer. Methods: In a prospective study consecutive 75 symptomatic patients with advanced head & neck cancer (squamous cell) attending hospital for palliative care following failure of standard therapy were administered Mw once a week for 8 weeks. Results: Of 75 patients 43 were male & 32 females with 76% between the ages of 31 to 60). 18 had buccal mucosa tumor, 12 alveolar and 11 at base of the tongue. Partial response was seen in 27. It was associated with Pain relief (27/27), Healing of ulcer/fistula (4/5), improvement in dysphagia (7/15), improvement in voice(5/19). All 27 showed improvement in constitutional symptoms also. No systemic side effects were seen. Conclusions: Mw vaccine is useful in palliative care of head & neck cancer. Reference 1Sur PK, Dastidar AG. Role of mycobacterium w as adjuvant treatment of lung cancer. J Indian Med Assoc. 2003;101:118, 120. 2Chaudhuri P, Mukhopadhyay S. Bladder preserving approach for muscle invasive bladder cancer–role of mycobacterium w. J Indian Med Assoc. 2003;101:559–60 3M. C. Pant, R. Hadi, R. Prasad, D. Dalela, et al. Role of immuno-therapy as a adjuvant treatment in advance head & neck cancer, patient receiving chemo radiotherapy. Journal of Clinical Oncology 2005; 23, (16S Part 1): 190S 4S. K. Sarkar, C. Dasgupta. Role of Mycobacterium W as an adjuvant treatment of Head & Neck Cancer_A Randomised trial. Journal of Clinical Oncology 2005; 23, (16S Part 1): 521 s. No significant financial relationships to disclose.

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.