Osteoradionecrosis versus Cancer Recurrence: An Unresolved Clinical Dilemma.

INTRODUCTION: Osteoradionecrosis is a rare and debilitating risk of definitive chemoradiotherapy for head and neck squamous cell carcinoma. It is difficult to distinguish between osteoradionecrosis and recurrent or progressive disease, as clinical and radiologic features may be similar. Our aim was to compare the clinical presentation and radiologic features of osteonecrosis with those of recurrent or progressive cancer. METHODS: We conducted a single-center case series of 19 patients with head and neck squamous cell carcinoma diagnosed between 2011 and 2019 who subsequently developed clinical and/or radiological suspicion of osteoradionecrosis. The population was a referred sample from head and neck cancer physicians at Northwell Health Cancer Institute. Clinician notes and imaging reports were reviewed to assign a final diagnosis of either cancer, osteonecrosis, or indeterminate. RESULTS: No differences were found in the clinical presentation or radiologic features between groups. Median time between treatment and development of symptoms was longer in patients with a final diagnosis of osteoradionecrosis than recurrent or progressive disease (5 vs. 3 months), but this difference was not statistically significant. Radiation dose and type were not associated with diagnosis. Mean standard uptake value maximums on positron emission tomography/computed tomography were significantly higher in the cancer group (median 14.8 vs. 9.1, p < 0.0152). At 1 year after first suspicion of osteoradionecrosis, 100% of osteoradionecrosis patients were alive, versus 28.6% of cancer patients. DISCUSSION/CONCLUSION: There is significant overlap in clinical and radiologic features of osteoradionecrosis and cancer. Standard uptake maximums may be helpful in predicting diagnosis. Occurrence of symptoms within 6 months of completing chemoradiotherapy should raise the concern for malignancy.

Missed Opportunities? An Observational Analysis of Lung Cancer Screening Utilization Amongst Patients With Lung Cancer.

Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. The U.S. Preventive Services Task Force (USPSTF) and National Comprehensive Cancer Network (NCCN) recommend annual low-dose CT chest (LDCT) for LC screening in high-risk adults who meet appropriate criteria, which primarily focus on age and smoking history. Despite this, screening rates remain low and patients with LC are typically diagnosed at a later stage.We conducted a single-center retrospective analysis of patients with an established diagnosis of lung cancer to evaluate if screening guidelines were appropriately followed before the cancer diagnosis.Patients diagnosed with LC between 2016 and 2019 were included in the analysis. Charts were reviewed for demographics, detailed smoking history, as well as histology and stage of LC. Associations between categorical factors and screening were examined using the chi-square test. Associations between continuous and ordinal factors and screening were examined using the Mann-Whitney test.A total of 530 charts were reviewed, of which 52% met NCCN criteria and 35% met USPSTF criteria. Only 4.0% and 4.8% of patients who met NCCN and USPSTF criteria, respectively, underwent screening. There was a significant association between staging at diagnosis and screening with LDCT. All the patients who had screening CT scans were diagnosed at localized stages of lung cancer in both NCCN and USPSTF groups compared to 49.1% and 48% in eligible subjects that did not undergo screening, respectively.Our study showed that despite established guidelines for LC screening and insurance coverage, a vast majority of screening-eligible LC patients have never had LDCT. We found that patients who underwent screening as per guidelines were diagnosed at earlier stages of the disease. Ongoing efforts to increase awareness and adherence to LC screening guidelines are needed to improve early detection and reduce LC mortality.

A real world analysis of first line treatment of advanced EGFR mutated non-small cell lung cancer: A multi-center, retrospective study.

INTRODUCTION: The recently published FLAURA trial demonstrated that osimertinib has remarkable efficacy in front-line setting for non-small cell lung cancer (NSCLC). While this has transformed current practice, there are no effective treatments following progression on osimertinib. The aim of our study was to compare progression-free survival (PFS) and overall survival (OS) between patients initiated on osimertinib to those started on other EGFR TKIs. METHODS: This was a multicenter, retrospective study conducted at two large academic centers. Adult patients with EGFR-mutated non-small cell lung cancer (NSCLC) who received EGFR therapy between 2014 and 2019 were included. Patients were dichotomized based on front-line TKI (osimertinib vs. other). PFS, OS, and time-to-discontinuation were evaluated. RESULTS: One-hundred seventy-two patients were included in the final analysis. Fifty-two (30.2%) patients received osimertinib and 120 (69.8%) patients received another EGFR TKI. The PFS rates at 6, 12, and 18 months were 86.3%, 79.5%, 69.8% in the osimertinib group and 86.6%, 64.2%, 39.3% in the other EGFR TKI group, respectively (p < 0.0036).Estimated OS at 6, 12, and 18 months was similar for both groups: 94.2%, 94.2%, 80.2% and 95.7%, 93.9%, 84.1%, respectively [Adjusted HR = 0.95 (95% CI, 0.37-2.44; p < 0.9128]. CONCLUSION: Osimertinib demonstrated greater 12 and 18 month PFS compared to other EGFR TKIs. This finding is consistent with results of the FLAURA trial. However, unlike FLAURA, there were no differences in estimated OS between the two groups in our study. Further research to evaluate optimal sequencing strategies in the real world of first, second and third generation TKIs is needed.

Impact of Family and Social Network on Tobacco Cessation Amongst Cancer Patients.

Continued smoking after a cancer diagnosis adversely affects outcomes, including recurrence of the primary cancer and/or the development of second primary cancers. Despite this, prevalence of smoking is high in cancer survivors and higher in survivors of tobacco-related cancers. The diagnosis of cancer provides a teachable moment, and social networks, such as family, friends, and social groups, seem to play a significant role in smoking habits of cancer patients. Interventions that involve members of patients' social network, especially those who also smoke, might improve tobacco cessation rates. Very few studies have been conducted to evaluate and target patients' social networks. Yet, many studies have demonstrated that cancer survivors who received higher levels of social support were less likely to be current smokers. Clinicians should be doing as much as they can to encourage smoking cessation in both patients and relevant family members. Research aimed at influencing smoking behavioral change in the entire family is needed to increase cessation intervention success rate, which can ultimately improve the health and longevity of patients as well as their family members.

Lorlatinib induced proteinuria: A case report.

INTRODUCTION: Lorlatinib is an oral anaplastic lymphoma kinase (ALK) and C-ros oncogene (ROS1) tyrosine kinase inhibitor with excellent central nervous system (CNS) penetrability. It is currently approved for use as second line therapy for those with ALK positive non-small cell lung cancer (NSCLC). Given its CNS penetrating effects, lorlatinib has shown to cause CNS adverse events such as seizures, hallucinations, and changes in cognitive function. To our knowledge proteinuria has not been previously described with this medication. CASE REPORT: We report a case lorlatinib induced proteinuria in a patient receiving lorlatinib as second line treatment for ROS1 rearranged NSCLC.Management & Outcome: The patient's dose was reduced from 100 mg to 75 mg and further down to to 50 mg daily. At that point the proteinuria improved. Other adverse events attributable to the medication, specifically hallucinations and peripheral neuropathy also improved. DISCUSSION: Our case demonstrates objective evidence for proteinuria induced by lorlatinib, which may also be dose dependent.

Identifying patterns of failure and secondary primary malignancies in HPV-related oropharyngeal squamous cell carcinomas.

Aim: To compare patterns and rates of recurrence in patients with oropharyngeal squamous cell carcinoma by human papilloma virus (HPV) status. Patients & methods: Retrospective chart review of 155 patients diagnosed with oropharyngeal squamous cell carcinoma between 2012 and 2014 at a single center. Results: Two-year recurrence-free survival was higher in patients with HPV-positive tumors compared with negative (85.2% [standard error = 0.03] versus 59.3% [standard error = 0.09]; p < .001) with the former proportionally less likely to have locoregional recurrence. HPV-positive patients had proportionally higher incidence of second primary malignancies outside of head, neck and lung compared with HPV-negative (74.2 vs 37.5%; p = 0.09). Conclusion: The differences in failure by HPV status indicates a need for modified surveillance guidelines. The differences in second primary malignancies patterns are interesting, warranting further evaluation in larger studies.

Hyperpigmentation due to imatinib: A rare case of cutaneous involvement.

CASE REPORT: Imatinib mesylate is a well-known tyrosine kinase inhibitor used to treat chronic myeloid leukemia, gastrointestinal stromal tumor, as well as a variety of other malignancies.Management and outcome: As use of this medication continues to grow, providers must be aware of potential side effects and management thereof. The toxicity profile of imatinib has been well characterized with most patients experiencing a grade 1 or 2 adverse event. These side effects are usually mild, and most patients can continue treatment without interruption. Around 30% of patients on imatinib experience skin toxicity, with 5% being high grade. This rash is typically hypopigmented, which is explained by imatinib's effect on melanocytes. DISCUSSION: Although there have been several case reports describing hyperpigmentation of the oral mucosa or nails, very few have described skin hyperpigmentation. We previously reported the first two cases of imatinib-related squamous cell carcinoma in patients undergoing treatment for gastrointestinal stromal tumors. In this paper, we present a case of a patient on imatinib for management of gastrointestinal stromal tumor who experienced extensive skin hyperpigmentation and review the literature.

Management of the neck after definitive chemoradiation in patients with HPV-associated oropharyngeal cancer: An institutional experience.

PURPOSE: To investigate the multidisciplinary management of patients with Human Papilloma Virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) and an incomplete nodal response on restaging PET/CT after definitive chemoradiation (CRT). MATERIALS AND METHODS: A retrospective chart review was performed of patients diagnosed with node-positive HPV-associated OPSCC from 2012 to 2017, who underwent definitive upfront CRT, and had an incomplete response on post-therapy PET/CT according to NCCN criteria. Post-CRT PET/CT results, management decisions, and clinical outcomes were recorded. RESULTS: Seventy-four patients with node-positive HPV-associated OPSCC were identified; 20 patients with incomplete neck response on PET/CT according to NCCN criteria were included in the final case series. Median follow-up time was 33 months. Patients were managed as follows: 8 underwent observation and surveillance imaging, 6 underwent ultrasound-guided fine needle aspiration (FNA), and 6 had immediate neck dissection. All the observed patients were disease-free at most recent follow-up. None of the patients who underwent immediate neck dissection had residual neck disease on pathological examination; two patients in this group ultimately developed metastatic disease. Among the 6 who underwent FNA, 1 individual had positive pathology, along with residual primary disease, for which the patient underwent salvage surgery. The 5 remaining individuals had negative FNA results, were subsequently observed, and remained free of disease. CONCLUSIONS: This institutional experience supports the notion of a high threshold for neck dissection in this low-risk population; only 1 of 20 patients with suspicious PET/CT findings had residual disease in the neck. Moreover, these patients should be managed by a multidisciplinary tumor board (MTB) since current algorithms do not universally include HPV status. Finally, the use of restaging PET/CT to guide management of the neck can be improved with changes in terminology and consideration of FDG-avidity at the primary site and on pre-therapy scans.

Bi-specific and tri-specific antibodies- the next big thing in solid tumor therapeutics.

Antibody-based therapy has revitalized the world of cancer therapeutics since rituximab was first approved for the treatment of Non-Hodgkin's Lymphoma. Monoclonal antibodies against cancer antigens have been successful strategies for only a handful of cancer types due to many reasons including lack of antibody specificity and complex nature of tumor milieu which interfere with antibody efficacy. Polyspecific antibodies are promising class of anti-cancer agents which can be directed at multiple tumor antigens to eradicate tumor cells more precisely and effectively. They may overcome some of these limitations and have already changed treatment landscape for some malignancies such as B cell acute lymphoblastic leukemia. Pre-clinical studies and early phase clinical trials have demonstrated that this approach may be an effective strategy even for solid tumors. This review focuses on the development of bispecific and trispecific antibody therapy for the treatment of solid tumor malignancies and highlights the potential they hold for future therapies to come.

Immune checkpoint inhibitors in lung cancer: past, present and future.

Inhibitory ligands on tumor cells and their corresponding receptors on T cells are collectively called immune checkpoint molecules and have emerged as druggable targets that harness endogenous immunity to fight cancer. Immune checkpoint inhibitors targeting CTLA-4, PD-1 and PD-L1 have been developed for the treatment of patients with non-small-cell lung cancer and other malignancies, with impressive clinical activity, durable responses and a favorable toxicity profile. This article reviews the development, current status and future directions for some of these agents. The efficacy and safety data for drugs such as ipilimumab, nivolumab, pembrolizumab, atezolizumab and durvalumab are reviewed, along with combination strategies and response evaluation criteria. The toxicity profiles and predictive biomarkers of response are also discussed.

A phase II study of pralatrexate with vitamin B12 and folic acid supplementation for previously treated recurrent and/or metastatic head and neck squamous cell cancer.

BACKGROUND: Pralatrexate (Fotolyn(TM); Allos Therapeutics Inc.) is an antifolate dihydrofolate reductase (DHFR) inhibitor. We conducted a phase II study of pralatrexate with folic acid and B12 supplementation in patients with recurrent and/or metastatic head and neck squamous cell cancer (R/M HNSCC). PATIENTS AND METHODS: This was a single-arm, Simon optimal two stage phase II study. Patients with R/M HNSCC previously treated with chemotherapy were eligible. The study was initiated with a dosing schedule of pralatrexate 190 mg/m(2) biweekly on a 4-week cycle with vitamin supplementation. Due to toxicity concerns, the dosing was modified to 30 mg/m(2) weekly for 3 weeks in a 4-week cycle with vitamin supplementation. Radiologic imaging was to be obtained about every 2 cycles. RESULTS: Thirteen subjects were enrolled; 12 were treated. Seven of the twelve patients had previously received ≥2 lines of chemotherapy. The most common grade 3 toxicity was mucositis (3 patients). Seven patients did not complete two cycles of therapy due to progression of disease (4), toxicity (1), death (1), and withdrawal of consent (1). Two deaths occurred: one due to disease progression and the other was an unwitnessed event that was possibly related to pralatrexate. No clinical activity was observed. The median overall survival was 3.1 months. The study was closed early due to lack of efficacy. CONCLUSIONS: Pralatrexate does not possess clinical activity against previously treated R/M HNSCC. Evaluation of pralatrexate in other clinical settings of HNSCC management with special considerations for drug toxicity may be warranted.

Proteasome inhibition paradoxically degrades gain-of-function mutant p53 R273H in NSCLC and could have therapeutic implications.

Lung cancer is the leading cause of cancer mortality. Despite therapeutic advances in recent years, new treatment strategies are needed to improve outcomes of lung cancer patients. Mutant p53 is prevalent in lung cancers and drives several hallmarks of cancer through a gain-of-function oncogenic program, and often predicts a poorer prognosis. The oncogenicity of mutant p53 is related to its stability and accumulation in cells by evading degradation by the proteasome. Therefore, destabilization of mutant p53 has been sought as a therapeutic strategy, but so far without clinical success. In this study, we report that proteasome inhibition results in degradation of mutant p53 in non-small cell lung cancer (NSCLC) cell lines bearing the R273H mutant protein and show evidence that this was mediated by hsp70. NSCLC cell lines with the mutant R273H allele demonstrated increased susceptibility and apoptosis to proteasome inhibitors. These data suggest that proteasome inhibitors could have therapeutic implications in some subsets of TP53 mutated NSCLC.

Clinical predictors of premature radiotherapy terminations in senior adults with oral cavity and laryngeal carcinoma.

INTRODUCTION: The underlying factors that contribute to early radiotherapy (RT) termination are understudied, especially in the era of hypofractionated treatment regimens. In this retrospective investigation, we examined the characteristics and causes of premature RT terminations in senior adults (>70 years old) with oral cavity (OC) and laryngeal carcinomas. METHODS: Hundred and eighty-eight patients treated with RT ± systemic therapy for OC and laryngeal cancer from 2017 to 2022 were identified. Premature termination was defined as completion of less than 95% of the prescribed RT. Logistic regression analysis was performed to examine factors predictive of premature termination, and survival was determined using the Kaplan-Meier method. RESULTS: Twenty patients (10.6%) experienced premature RT terminations. On regression analysis, ECOG score at initiation of RT was the only covariate studied to be independently associated with premature termination (OR 2.00, 95%CI: [1.21, 3.30], p = 0.007). Three-year overall survival (49.1% vs. 77.3%) was significantly reduced in the termination cohort (p < 0.0001). CONCLUSIONS: This analysis demonstrated over 1 in 10 patients had premature RT termination, which prognosticated inferior survival outcomes. Poor performance status may highlight patients at risk for premature termination and thus identify good candidates for hypofractionated protocols.

Rates of Occult Invasive Disease in Patients With Biopsy-Proven Oral Cavity Squamous Cell Carcinoma in Situ.

Importance: The likelihood that an oral cavity lesion harbors occult invasive disease after biopsy demonstrating carcinoma in situ (CIS) is unknown. While de-escalated treatment strategies may be appealing in the setting of CIS, knowing whether occult invasive disease may be present and its association with survival outcomes would lead to more informed management decisions. Objective: To evaluate rate of occult invasive disease and clinical outcomes in patients with oral cavity CIS. Design, Setting, and Participants: This was a retrospective population-based cohort study using the National Cancer Database and included adults with biopsy-proven oral cavity CIS as the first diagnosis of cancer between 2004 and 2020. Data were analyzed from October 10, 2022, to June 25, 2023. Exposures: Surgical resection vs no surgery. Main Outcomes and Measures: Analyses calculated the rate of occult invasive disease identified on resection of a biopsy-proven CIS lesion. Univariate and multivariate logistic regression with odds ratios and 95% CIs were used to identify significant demographic and clinical characteristics associated with risk of occult invasion (age, year of diagnosis, sex, race and ethnicity, oral cavity subsite, and comorbidity status). Kaplan-Meier curves for overall survival (OS) were calculated for both unresected and resected cohorts (stratified by presence of occult invasive disease). Results: A total of 1856 patients with oral cavity CIS were identified, with 122 who did not undergo surgery (median [range] age, 65 [26-90] years; 48 female individuals [39.3%] and 74 male individuals [60.7%]) and 1458 who underwent surgical resection and had documented pathology (median [range] age, 62 [21-90] years; 490 female individuals [33.6%] and 968 male individuals [66.4%]). Of the 1580 patients overall, 52 (3.3%) were Black; 39 (2.5%), Hispanic; 1365 (86.4%), White; and 124 (7.8%), other, not specified. Among those who proceeded with surgery with documented pathology, 408 patients (28.0%) were found to have occult invasive disease. Higher-risk features were present in 45 patients (11.0%) for final margin positivity, 16 patients (3.9%) for lymphovascular invasion, 13 patients (3.2%) for high-grade invasive disease, and 14 patients (3.4%) for nodal involvement. For those patients with occult disease, staging according to the American Joint Committee on Cancer's AJCC Cancer Staging Manual, eighth edition, was pT1 in 341 patients (83.6%), pT2 in 41 (10.0%), and pT3 or pT4 disease in 26 (6.4%). Factors associated with greater odds of occult invasive disease at resection were female sex, Black race, and alveolar ridge, vestibule, and retromolar subsite. With median 66-month follow-up, 5-year OS was 85.9% in patients who proceeded with surgical resection vs 59.7% in patients who did not undergo surgery (difference, 26.2%; 95% CI, 19.0%-33.4%). Conclusions and Relevance: This cohort study assessed the risk of concurrent occult invasion with biopsy-proven CIS of the oral cavity, demonstrating that 28.0% had invasive disease at resection. Reassuringly, even in the setting of occult invasion, high-risk disease features were rare, and 5-year OS was nearly 80% with resection. The findings support the practice of definitive resection if feasible following biopsy demonstrating oral cavity CIS.

Implementing physician education to increase lung cancer screening uptake.

Aim: Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. The US Preventive Services Task Force and National Comprehensive Cancer Network recommend annual low-dose computed tomography (LDCT) for eligible adults. We conducted a study to assess physician LDCT referral patterns. Methods: The study was divided into a pre-, intervention, and post-intervention periods. The intervention was a LC screening educational series. We evaluated rates of LDCT screening referrals during pre- and post-intervention periods. Results: In the pre-intervention period, 75 patients fulfilled US Preventive Services Task Force and/or National Comprehensive Cancer Network criteria and 27% underwent LDCT. In the post-intervention period, 135 patients fulfilled either screening criteria of whom 61.5% underwent LDCT. Conclusion: In our study, educational lectures improved compliance significantly and should be used as tool for primary care providers to effectively increase LDCT screening referrals.

Profile of Capmatinib for the Treatment of Metastatic Non-Small Cell Lung Cancer (NSCLC): Patient Selection and Perspectives.

Aberrant c-MET (Mesenchymal-Epithelial Transition) signaling contributes to cancer cell development, proliferation, and metastases of non-small cell lung cancer (NSCLC). MET exon 14 (METex14) skipping mutation is noted in approximately 4% of NSCLC cases and is targetable with the recently approved tyrosine kinase inhibitors capmatinib and tepotinib. Capmatinib, the focus of this review article, is a highly selective MET inhibitor approved for use in patients with METex14 mutated NSCLC. In this review, we discuss cMET as a target, the pharmacology of capmatinib, key trials of capmatinib in MET-altered lung cancer, and toxicity profile. We highlight some ongoing capmatinib clinical trials that expand their role to other subsets of patients, especially those with EGFR mutations, who develop MET alterations as a resistance pathway. We further provide our perspective on the management of METex14 NSCLC, strategies for sequencing agents, and toxicity management.

Safety and Efficacy of Immune Checkpoint Inhibitors in Cancer Patients and Preexisting Autoimmune Disease: A Systematic Review and Meta-Analysis in Non-Small-Cell Lung Cancer.

BACKGROUND: Cancer patients with preexisting autoimmune diseases (AID) have been traditionally excluded from clinical trials of immune checkpoint inhibitors (ICI) due to concerns for toxicity. As indications for ICI expand, more data are needed on the safety and efficacy of ICI treatment in cancer patients with AID. METHODS: We systematically searched for studies consisting of NSCLC, AID, ICI, treatment response, and adverse events. Outcomes of interest include incidence of autoimmune flare, irAE, response rate, and ICI discontinuation. Study data were pooled using random-effects meta-analysis. RESULTS: Data were extracted from 24 cohort studies, consisting of 11,567 cancer patients (3774 NSCLC patients and 1157 with AID). Pooled analysis revealed an AID flare incidence of 36% (95% CI, 27%-46%) in all cancers and 23% (95% CI, 9%-40%) in NSCLC. Preexisting AID was associated with an increased risk of de novo irAE in all cancer patients (RR 1.38, 95% CI, 1.16-1.65) and NSCLC patients (RR 1.51, 95% CI, 1.12-2.03). There was no difference in de novo grade 3 to 4 irAE and tumor response between cancer patients with and without AID. However, in NSCLC patients, preexisting AID was associated with a 2-fold increased risk of de novo grade 3 to 4 irAE (RR 1.95, 95% CI, 1.01-3.75) but also better tumor response in achieving a complete or partial response (RR 1.56, 95% CI, 1.19-2.04). CONCLUSIONS: NSCLC patients with AID are at a higher risk of grade 3 to 4 irAE but are more likely to achieve treatment response. Prospective studies focused on optimizing immunotherapeutic strategies are needed to improve outcomes for NSCLC patients with AID.

Harmine loaded Au@MSNs@PEG@Asp6 nano-composites for treatment of spinal metastasis from lung adenocarcinoma by targeting ANXA9 in vivo experiment.

Background: Annexin A9 (ANXA9) has been proved to be concerned with cancer development. However, to explore the clinical consequences of ANXA9 in lung adenocarcinoma (LUAD), especially its correlation to spinal metastasis (SM) has no in-depth study. The study was expected to elucidate the mechanism of ANXA9 in regulating SM of LUAD and create a productive nano-composites delivery system targeting this gene for treatment of SM. Methods: Harmine (HM), a ß-carboline extracted from the traditional Chinese herb Peganum harmala, loaded Au@MSNs@PEG@Asp6 (NPS) nano-composites were synthesized. Bioinformatics analysis and clinical specimens' tests were used to verify the association between ANXA9 and prognosis of LUAD with SM. The immunohistochemistry (IHC) was employed to detect the expression levels of the ANXA9 protein in LUAD tissues with or without SM, and its significance in clinic was also explored. ANXA9­siRNA was applied to investigate the molecular mechanism of ANXA9 in tumor behaviors. The HM release kinetics was detected by high performance liquid chromatography (HPLC) method. The cellular uptake efficiency of nanoparticles by A549 cells was observed by fluorescence microscope. Antitumor effects of nanoparticles were assessed in the nude mouse model of SM. Results: The genomic amplification of ANXA9 was prevalent in LUAD tissues and closely associated with poor outcome and SM (P<0.01). The experimental result manifested that high expression of ANXA9 could lead to wretched prognosis and ANXA9 was an independent risk factor for survival (P<0.05). After impeding expression of ANXA9, the proliferation and metastatic ability of tumor cells obviously decreased, and expression of matrix metallopeptidase 2 (MMP-2) and matrix metallopeptidase 9 (MMP-9) were considerably downregulated, while the expression of associated oncogene pathway were downregulated (P<0.01) as well. The synthesized HM-loaded NPS nano-composites could target to cancer and response to reactive oxygen species (ROS) to release HM slowly. Notably, in comparison to free HM, the nano-composites showed excellent targeting and anti-tumor effects in the A549 cell-bearing mouse model. Conclusions: ANXA9 may serve as a novel biomarker for predicting poor prognosis in LUAD, and we provided an efficient and targeting drug delivery nano-composites system for precise treatment of SM from LUAD.