Treatment Of Primary Lung Cancer Research Articles

Current status of lung cancer care in Germany in the context of treatment centralization and lack of personnel

Lung cancer is the malignancy with the highest mortality rate worldwide. In January 2025, the German public healthcare system will introduce a new regulation according to which a centre can offer surgery for lung cancer only if it carries out a minimum number of lung resections. The purpose of this directive is to reduce the number of centres offering surgical treatment for primary lung cancer, thus centralising and improving lung cancer care. It is expected that the introduction of this regulation will lead to a significant shift in the staffing of thoracic units. The purpose of this survey was to examine the current occupational structures behind the units of thoracic surgery and respiratory medicine. We performed an online survey through the German Society for Thoracic Surgery and the Association of Respiratory Physicians. The responding centres were divided in two groups, centres that were certified by the German Cancer Society or the Society for Thoracic Surgery and centres which were not certified. The response rate was 29.3% (respiratory physicians) and 31.9% (thoracic surgeons); 67% of the participating colleagues answered that their unit was an independent department. The majority of the participants reported having to share the on-call duty of the trainees with other departments in order to be able to cover the required shifts. 35% of the respiratory physicians and 57% of the thoracic surgeons reported having vacant job posts in their units. The introduction of the minimum quantity regulation will have significant consequences for the treatment of lung cancer in Germany. The current staff shortage in healthcare will lead to both medical and nursing staff needing to be redistributed in order to meet the needs that will arise in 2025. Operating lists, theatre days, and operative equipment will need to be redistributed as well, not only within hospitals but probably on a nationwide level. A negative impact of the new regulation is to be expected on research and academic activities since most university hospitals are not expected to reach the minimum number of lung resections that is required in order keep performing lung cancer surgery.

Impact of perioperative high-protein nutritional support on postoperative outcomes in the treatment of primary lung cancer: Russian prospective multicenter comparative study (NUTRILUNC-study)

BACKGROUND: Up to 60% of lung cancer pts experience weight loss. Prevalence of sarcopenia in patients (pts) with non-small cell lung cancer (NSCLC) is about 43% and is an independent predictor of worse overall survival. It was shown that nutritional support improves outcomes in pts with cancer. AIM: To evaluate impact of perioperative nutritional support on surgical treatment outcomes of patients with NSCLC. MATERIALS AND METHODS: Patients with primary NSCLC (n=112, 69 males), aged 57,2±8,2, awaiting lung surgery and being at risk of malnutrition (Nutritional Risk Screening Assessment 2002 score ≥3) were randomized into 2 groups. Study group (n=55) received oral nutritional support (Nutridrink Compact Protein, Nutricia LLC), 250 ml/d (36 g of protein, 612 kcal) for 14 d before and 14 d after surgery in addition to standard diet. Control group (n=57) had a standard diet. The number of respiratory complications after surgery, length of hospitalization, anthropometric, functional, laboratory parameters, quality of life (according to Quality of Life Questionnaire Core-30) were assessed. Results were presented as mean ± standard deviation. Differences were considered significant at p ≤0.05. RESULTS: In the study group there were fewer respiratory complications (p 0.01), and a shorter length of hospitalization (p=0.03). Body weight in the study group did not change significantly, while in the control group it decreased (0.15±3.7 kg versus loss of 3.47±3.6 kg). Results of six-minute walk test and hand grip dynamometry were higher in the study group then in the control group (411.8±56.0 m versus 383.2±52.1 m; 33.5±8.4 kg versus 27.1±6.8 kg). Quality of life was better in the study group, p 0.05. The total protein and albumin levels were higher in the study group (70.9±5.6 g/l versus 63.1±4.0 g/l; 38.5±5.8 g/l versus 33.2±3.0 g/l). One patient in study group experienced 1st grade diarrhea. CONCLUSION: In patients with NSCLC at risk of malnutrition perioperative nutritional support with high protein oral nutritional support has a positive effect on surgical treatment outcomes.

Inhalable dry powders of microRNA-laden extracellular vesicles prepared by thin-film freeze-drying

Extracellular vesicles (EVs) are endogenous vesicles that comprise a variety of submicron vesicular structures. Among these, exosomes have been widely investigated as delivery systems for small and large molecules. Herein, the thin-film freeze-drying technology was utilized to engineer aerosolizable dry powders of miR-335-laden induced EVs (iEV-335) generated in B cells for potential delivery into the lung to treat primary lung cancer and/or pulmonary metastases. The size distribution, structure, and morphology of iEV-335 were preserved after they were subjected to thin-film freeze-drying with the proper excipients. Importantly, iEV-335, in liquid or reconstituted from thin-film freeze-dried powders, were equally effective in downregulating SOX4 gene expression in LM2 human triple-negative mammary cancer cells. The iEV-335 dry powder compositions showed mass median aerodynamic diameters (MMAD) of around 1.2 µm with > 60 % of the emitted doses had an MMAD of ≤ 3 µm, indicating that the powders can potentially achieve efficient deposition within the alveolar region following oral inhalation, which is desirable for treatment of primary lung cancer and pulmonary metastases. Overall, it is concluded that it is feasible to apply thin-film freeze-drying to prepare aerosolizable dry powders of iEVs for pulmonary delivery.

Impact of perioperative high-protein nutritional support on postoperative outcomes in the treatment of primary lung cancer: A multicenter comparative low-intervention study

Impact of perioperative high-protein nutritional support on postoperative outcomes in the treatment of primary lung cancer: A multicenter comparative low-intervention study

Identification of the Key Active Pharmaceutical Ingredients of Yishen Qutong Granule, A Chinese Medicine Formula, In The Treatment of Primary Lung Cancer.

Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. Traditional Chinese medicine (TCM) reportedly has potential therapeutic effects against LC. This study aimed to investigate the antitumor efficacy of Yishen Qutong granule (YSQTG) in primary LC treatment, to identify its key active pharmaceutical ingredients (APIs), and to explore its possible mechanism of action. The antitumor role of YSQTG was validated via cell function assays and a xenograft tumor model. Then, high-performance liquid chromatography-mass spectrometry (HPLC-MS) was performed to determine the objective precipitation components of YSQTG, followed by target prediction through reference to databases. Subsequently, the proportion of the predicted targets that underwent actual changes was identified via RNA-sequencing. Enrichment analysis was performed to explore the possible mechanisms of action. Hub genes were screened, and western blotting was used to verify their protein expression levels to identify the core target. Molecular docking between the active compounds and the verified core target was performed, combined with an evaluation of the potential efficacy of candidate compounds using meta-analysis to screen the candidate key APIs. Experiments confirmed that YSQTG could inhibit LC cell proliferation, induce apoptosis in vitro, and inhibit lung tumor growth in vivo. HPLC-MS, RNA-seq, and enrichment analysis showed that oxidative stress-related pathways were the possible mechanism of YSQTG in primary LC treatment. Western blot verification indicated that heme oxygenase 1 (HMOX1, HO-1) could be the core target. Molecular docking and meta-analysis suggested that genistein and quercetin were the candidate key APIs. YSQTG and its active ingredients, genistein and quercetin, may have therapeutic effects against LC through their action on the downregulation of oxidative stress-related HMOX1 protein expression.

The impact of perioperative high-protein oral nutrition supplements on postoperative outcomes in primary lung cancer: the protocol of Russian prospective, randomised, multicenter study

BACKGROUND: Nutritional support, including oral nutrition supplements, is an integral part of anticancer treatment, including during surgical treatment of non-small cell lung cancer. Existing evidence for the effectiveness of nutritional support in this cohort of patients is limited. We suggest that the perioperative administration of a balanced polymeric hypercaloric high-protein enteral nutritional formula by sipping as an additional nutrition can have a positive effect on the results of surgical treatment.
 AIMS: 1) to assess the impact of perioperative nutritional support with high-protein oral nutrition supplements on the risk of postoperative complications, postoperative recovery of respiratory functions, nutritional status and quality of life in patients with primary lung cancer; 2) identification of possible side effects and complications when using high-protein high-energy oral nutrition supplements in patients with non-small cell lung cancer.
 MATERIALS AND METHODS: Russian prospective, randomised, multicenter low-intervention study of perioperative effect of high-protein nutritional support on postoperative outcomes in the treatment of primary lung cancer with parallel groups, 1:1 randomization. The study will include 114 patients with primary non-small cell lung cancer who are scheduled for surgery. It is expected to provide nutritional support in the perioperative period for 14 days before surgery and for 14 days after it.
 CONCLUSION: The present study may become one of the first evidence-based studies confirming the effectiveness of perioperative nutritional support with high-protein mixtures in patients with non-small cell lung cancer and will allow further study of the strategy of nutritional support in this category of patients.

Update on Image-Guided Thermal Lung Ablation: Society Guidelines, Therapeutic Alternatives, and Postablation Imaging Findings

Percutaneous image-guided thermal ablation (IGTA) has been endorsed by multiple societies as a safe and effective lung-preserving treatment of primary lung cancer and metastases involving the lung and chest wall. This article reviews the role of IGTA in the care continuum of patients with thoracic neoplasms and discusses strategies to identify the optimal local therapy considering patient and tumor characteristics. The advantages and disadvantages of percutaneous thermal ablation compared with surgical resection and stereotactic body radiotherapy are summarized. Principles of radiofrequency ablation, microwave ablation, and cryoablation, as well as the emerging use of transbronchial thermal ablation, are described. Specific considerations are presented regarding the role of thermal ablation for early-stage non-small cell lung cancer (NSCLC), multifocal primary NSCLC, pulmonary metastases, salvage of recurrent NSCLC after surgery or radiation, and pain palliation for tumors involving the chest wall. Recent changes to professional society guidelines regarding the role of thermal ablation in the lung, including for treatment of oligometastatic disease, are highlighted. Finally, recommendations are provided for imaging follow-up after thermal ablation of lung tumors, accompanied by examples of expected postoperative findings and patterns of disease recurrence.

Thoracoscopic segmentectomy and lobectomy assisted by three-dimensional computed-tomography bronchography and angiography for the treatment of primary lung cancer.

BACKGROUNDAnatomical segmentectomy has been proposed as a substitution for lobectomy for early-stage lung cancer. However, it requires technical meticulousness due to the complex anatomical variations of segmental vessels and bronchi.AIMTo assess the safety and feasibility of three-dimensional computed-tomography bronchography and angiography (3D-CTBA) in performing video-assisted thoracoscopic surgery (VATS) for lung cancers.METHODSIn this study, we enrolled 123 patients who consented to undergo thoracoscopic segmentectomy and lobectomy assisted by 3D-CTBA between May 2017 and June 2019. The image data of enhanced computed tomography (CT) scans was reconstructed three-dimensionally by the Mimics software. The results of preoperative 3D-CTBA, in combination with intraoperative navigation, guided the surgery.RESULTSA total of 59 women and 64 men were enrolled, of whom 57 (46.3%) underwent segmentectomy and 66 (53.7%) underwent lobectomy. The majority of tumor appearance on CT was part-solid ground-glass nodule (pGGN; 55.3%). The mean duration of chest tube placement was 3.5 ± 1.6 d, and the average length of postoperative hospital stay was 6.8 ± 1.8 d. Surgical complications included one case of pneumonia and four cases of prolonged air leak lasting > 5 d. Notably, there was no intraoperative massive hemorrhage, postoperative intensive-care unit stay, or 30-d mortality. Preoperative 3D-CTBA images can display clearly and vividly the targeted structure and the variations of vessels and bronchi. To reduce the risk of locoregional recurrence, the application of 3D-CTBA with a virtual 3D surgical margin help the VATS surgeon determine accurate distances and positional relations among the tumor, bronchial trees, and the intersegmental vessels. Three-dimensional navigation was performed to confirm the segmental structure, precisely cut off the targeted segment, and avoid intersegmental veins injury.CONCLUSIONVATS and 3D-CTBA worked in harmony in our study. This combination also provided a new pattern of transition from lesion-directed location of tumors to computer-aided surgery for the management of early lung cancer.

Assessment of National Comprehensive Cancer Network (NCCN) guideline adherence for lung cancer in a community teaching hospital during COVID-19 pandemic.

e20589 Background: Coronavirus disease 2019 (COVID-19) evolved into a worldwide pandemic leading to devastating complications. In healthcare, significant changes were made to reallocate resources to cater to an increasing number of hospital admissions and prevent infection spread. Reallocation of the health care staff led to the scarcity of care in outpatient facilities, including infusion centers, until the widespread adoption of Telehealth. Treating lung cancer patients with immunochemotherapy and radiotherapy has been incredibly challenging due to the pandemic, especially in regard to balancing malignancy treatment with limiting exposure of vulnerable patients to acute life-threatening infection. In addition, being unable to provide appropriate treatment to cancer patients can result in decreased functional capacity, loss of treatment window, and increased mortality. A multidisciplinary approach can prevent these outcomes by anticipating challenges early and streamlining resources appropriately to provide better patient care. In this study, we aimed to assess the adherence of NCCN guidelines for lung cancer at a community hospital in Philadelphia during the pandemic. Methods: A retrospective chart review was performed of patients diagnosed and receiving active treatment for primary lung cancer between March 1, 2020, and December 31, 2020, at Mercy Catholic Medical Center. Fifty cases of primary lung cancer undergoing active treatment were identified. Type and staging of lung cancer, NCCN guidelines’ adherence, COVID-19 exposure, and missed treatments were reviewed and analyzed. Results: Of the 50 cases reviewed, 92% had non-small cell lung cancer (NSCLC), and 8% had small cell lung cancer (SCLC). Among NSCLC, 72% had adenocarcinoma, 12% had squamous cell carcinoma, and 8% had large cell carcinoma. Stage IV lung cancer consisted of 46%, followed by 34% of stage I, 14% of stage III, and 6% of stage II. NCCN guideline-directed treatment was initiated in 88% (44/50) of the total patients, with the remaining 12% of the patients either refusing treatment (8%) or were lost to follow-up (4%). COVID-19 infection was diagnosed in 35% of the patients, of which 60% missed less than two chemotherapy sessions and 40% of COVID-19 positive patients who required hospitalization missed more than two cycles. 28% of patients missed treatment sessions due to other factors. This resulted in 61% (27/44) of patients having a disruption in NCCN guideline-directed treatment at some point during the pandemic. Conclusions: Our study results reflect upon the need for developing effective strategies in managing cancer patients. When possible, switching to oral regimens, redefining regimen administration intervals, postponing invasive investigations for asymptomatic patients, and utilizing telemedicine as appropriate should be considered.

372 Short- And Long-Term Outcome of Pneumonectomy for Lung Cancer: 20 Years’ Experience of a Single Centre

Abstract Introduction Surgery is the most important therapeutic modality for the treatment of primary lung cancer. Studies normally reported as 30-days or 90-days post-operative mortality or 5-years survival. However, survival for ≥10-years is rarely mentioned. Method Retrospective data collection from a tertiary centre database was implemented which include patients who underwent pneumonectomy from January 1998 until November 2019. The data was analysed for short and long-term outcomes including their respective Thoracoscore. Results 268 patients who had pneumonectomy were selected, in majority for lung cancer. 79.1% were male with mean age is 63. Overall operative mortality in this cohort was 4.9% while reported national mortality for pneumonectomy for lung cancer is 7%. No 30-days post-operative mortality in the last 5 years. The 5,10- and 15-years survival rate for patients are 36.9%, 23.9% and 20.3% respectively. This showed significant increase in the survival rate for 5- and 10-years post-pneumonectomy in comparison to previous study. Long-term survival was better in female with age <70 years. The overall survival rate >15 years is 0.4%. Conclusions This study shows that our operative mortality for pneumonectomy is significantly lower (30% less) than national mortality. This confirms that pneumonectomy is still an effective modality in the treatment of lung cancer.

Salvage surgery to treat tumor regrowth after stereotactic body radiotherapy in primary non-small cell lung cancer.

BackgroundStereotactic body radiotherapy (SBRT) is considered to be an effective and safe treatment in patients with primary lung cancer. If local recurrence is confirmed following SBRT, surgical treatment is a possibility. The present study aimed to clarify the safety and survival outcomes of salvage surgery in primary lung cancer patients with local recurrence following SBRT.MethodsAll subjects were patients with primary lung cancer who underwent surgical treatment for local recurrence following SBRT during the period from July 2005 to July 2015. We evaluated the reason for SBRT selection, the surgical procedure, postoperative complications, and prognosis.ResultsOf 932 patients underwent SBRT as treatment for primary lung cancer, 48 patients (5.2%) had local recurrence alone and 19 patients (2.0%) underwent salvage surgery. SBRT was selected in eight medically operable patients who refused surgery, and in 11 patients considered medically inoperable by their pulmonologist. Lobectomy was performed in 15 patients. Postoperative complications were documented in 4 patients (21.1%). Incomplete resection was performed in 2 patients. Stage progression was confirmed in 7 patients (36.8%). The 5-year overall survival (OS) was 72.5% and the 5-year disease-free survival (DFS) was 65.2%.ConclusionsWe evaluated patients who underwent salvage surgery due to local recurrence of lung cancer following SBRT. We found that salvage surgery could be performed safely without affecting SBRT outcomes. We further infer that cases of complete resection are likely to be associated with good prognosis, and that SBRT should be selected only after careful consideration because complete resection is not possible in all cases.

Contrast-enhanced T1-weighted image radiomics of brain metastases may predict EGFR mutation status in primary lung cancer

Identification of EGFR mutations is critical to the treatment of primary lung cancer and brain metastases (BMs). Here, we explored whether radiomic features of contrast-enhanced T1-weighted images (T1WIs) of BMs predict EGFR mutation status in primary lung cancer cases. In total, 1209 features were extracted from the contrast-enhanced T1WIs of 61 patients with 210 measurable BMs. Feature selection and classification were optimized using several machine learning algorithms. Ten-fold cross-validation was applied to the T1WI BM dataset (189 BMs for training and 21 BMs for the test set). Area under receiver operating characteristic curves (AUC), accuracy, sensitivity, and specificity were calculated. Subgroup analyses were also performed according to metastasis size. For all measurable BMs, random forest (RF) classification with RF selection demonstrated the highest diagnostic performance for identifying EGFR mutation (AUC: 86.81). Support vector machine and AdaBoost were comparable to RF classification. Subgroup analyses revealed that small BMs had the highest AUC (89.09). The diagnostic performance for large BMs was lower than that for small BMs (the highest AUC: 78.22). Contrast-enhanced T1-weighted image radiomics of brain metastases predicted the EGFR mutation status of lung cancer BMs with good diagnostic performance. However, further study is necessary to apply this algorithm more widely and to larger BMs.

Chemo-photodynamic therapy by pulmonary delivery of gefitinib nanoparticles and 5-aminolevulinic acid for treatment of primary lung cancer of rats.

Lung cancer is a severe disease with high mortality. Chemotherapy is one major treatment for lung cancer. However, systemic chemotherapeutics usually distribute throughout the body without specific lung distribution so that serious side effects are unavoidable. Photodynamic therapy (PDT) is occasionally used for lung cancer treatment but photosensitizers are also systemically administered and the bronchoscopic intervention under anesthesia may hurt lung tissues. Here, we combined inhaled chemotherapeutics and photosensitizers for chemo-photodynamic therapy (CPDT) of primary lung cancer of rats with external laser light irradiation. Gefitinib PLGA nanoparticles (GNPs) were prepared. The anti-cancer effects of GNPs and/or a common photosensitizer 5-aminolevulinic acid (5-ALA) were explored on A549 cells (adenocarcinomic human alveolar basal epithelial cells) and primary lung cancer rats after intratracheal administration. External light irradiation was applied due to its higher safety compared to internal light irradiation that may result in injuries after a laser optic fiber was intubated into the lung. The remarkable synergistic effect of CPDT was confirmed although the single therapies were also effective, where the high anti-lung cancer effects were shown and some typical lung cancer markers, including CD31, VEGF, NF-κB p65 and Bcl-2, significantly decreased. Moreover, the treatments attenuated inflammation with the downregulation of TNF-α. The combination of pulmonary drug delivery and chemo-photodynamic therapy is a promising strategy for treatment of lung cancer.

Comparative study of intratracheal and oral gefitinib for the treatment of primary lung cancer

Oral gefitinib tablets are widely applied for the treatment of non-small cell lung cancer (NSCLC) though its broad distribution in the body may result in weak therapeutic efficiency and undesired side effects. Here, liposomal gefitinib dry powder inhalers (LGDs) were prepared using the injection-lyophilization method. LGDs were rough porous particles under a scanning electron microscope, which can be rapidly rehydrated to liposomes. LGDs and gefitinib powders were separately intratracheally (i.t.) administered into the lungs of primary lung cancer rats, while powdered gefitinib tablets were orally administered. Gefitinib was rapidly absorbed from the lung after i.t. administration of LGDs. The maximal gefitinib concentration in the circulation and the area under curve (AUC) of i.t. LGDs were higher than those of i.t. gefitinib powders and oral gefitinib. More importantly, much higher concentration and longer retention of gefitinib in the lung were shown after i.t. administration of LGDs and gefitinib powders but remarkably less drug distribution in the liver compared to oral gefitinib. LGDs showed higher therapeutic effect on rat primary lung cancer than i.t. gefitinib powders and oral gefitinib with reduction of inflammation, weak lung injury, and high apoptosis. Combination of inhalation and liposomes of anticancer drugs is a promising strategy for treatment of primary lung cancer.

Paclitaxel-in-liposome-in-bacteria for inhalation treatment of primary lung cancer.

Bacterial therapy is emerging for the treatment of cancers though some scientific and clinical problems have not been addressed. Here, a live drug-loaded carrier, paclitaxel-in-liposome-in-bacteria (LPB), was prepared for inhalation treatment of primary lung cancer, where liposomal paclitaxel (LP) was highly effectively internalized into bacteria (E. coli or L. casei) to get LP-in-E. coli (LPE) or LP-in-L. casei (LPL) by electroporation that had no influence on the growth of these bacteria. Bacteria, LP, the simple mixture of LP and bacteria, and LPB remarkably inhibited the proliferation of A549 lung cancer cells, where LPE was the strongest one. Drug-loaded bacteria delivered the cargos into the cells more quickly than the mixture of drugs and bacteria and the cargos alone. LPE also showed the highest anticancer effect on the rat primary lung cancer among them with the downregulation of VEGF and HIF-1α and the improvement of cancer cell apoptosis after intratracheal administration. Moreover, the bacterial formulations significantly enhanced the expressions of immune markers (TNF-α, IL-4, and IFN-γ) and immune cells (leukocytes and neutrophils). LPB showed much higher bacterial distribution in the lung than other organs after intratracheal administration. LPB is a promising medicine for inhalation treatment of primary lung cancer.

Abstract 2191: Reduced clonogenic potential of patient-derived lung adenocarcinoma brain metastasis cells after in vitro application of Tumor Treating Fields (TTFields)

Abstract Up to 40% of all non-small cell lung cancer (NSCLC) patients will develop brain metastases during their disease, with ~25% of patients presenting with brain metastases at the time of their initial lung cancer diagnosis. For the latter patient population, median survival is a dismal 8 months. Systemic therapies are typically ineffective at treating the brain metastases, even in cases when the extracranial disease responds to the therapy. Clinical trials utilizing TTFields therapy in patients with lung cancer brain metastases are underway. For these trials, TTFields are delivered at 150 kHz, as that is the frequency that has been determined for the treatment of primary lung cancer. In contrast, for the FDA-approved treatment of the most common malignant primary brain tumor, glioblastoma, TTFields are delivered at 200 kHz. In our previous study, we found that 150 kHz TTFields decreased proliferation of patient-derived lung adenocarcinoma brain metastasis cells to a greater degree than 200 kHz. In this study, patient-derived lung adenocarcinoma brain metastasis cells were assessed for clonogenic potential after in vitro TTFields application at either 150 or 200 kHz and compared to untreated control cells. Methods: Use of patient tumor tissue for this study was approved by the Institutional Review Board and written informed consent was obtained from the patient. A lung adenocarcinoma brain metastasis tumor was collected immediately following microsurgical resection. A single-cell suspension from the tumor tissue was prepared by enzymatic and mechanical disruption. After 3-6 passages in vitro, cells were plated on plastic coverslips (5x104each) in DMEM/F12 media supplemented with 10% fetal bovine serum. TTFields were applied at ~1.6 V/cm at 150 or 200 kHz (groups n=3-6) with one control group. Culture media was replaced every day. After 14 days of in vitro TTFields application, cells were assayed for lactase dehydrogenase (LDH) release into the media and cells were harvested and replated for the clonogenic assay. Control vs. TTFields-treated groups were compared with one-way ANOVA. Results: TTFields application reduced LDH in the media ~15% at 150 kHz and ~30% at 200 kHz (p=0.0011). In the clonogenic assay, cell counts were markedly reduced after TTFields in both the 150 kHz (142.4±120.1) and 200 kHz (457.2±431.9) compared to the controls (9136±2735; p=0.0007) although the post-hoc Tukey analysis found no statistical difference between the two TTFields-treated groups. Conclusions: Application of TTFields in vitro at 150 and 200 kHz reduced LDH release into the media as well as the clonogenic potential of the patient-derived lung adenocarcinoma brain metastasis cells. Citation Format: Sharon K. Michelhaugh, Sam Kiousis, Sandeep Mittal. Reduced clonogenic potential of patient-derived lung adenocarcinoma brain metastasis cells after in vitro application of Tumor Treating Fields (TTFields) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2191.

Abstract 2906: Intratumor heterogeneity of non-small-cell lung cancer with EGFR mutations

Abstract The mutation frequency of epidermal growth factor receptor (EGFR) is approximately 40% among Asian patients with NSCLC. Guidelines for the diagnosis and treatment of primary lung cancer in China recommended epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) as a first-line therapy for advanced NSCLC patients carrying EGFR mutation including exon 19 deletion (19Del) and L858R mutation on exon 21 (L858R). Although survival periods in clinical practice of EGFR-TKIs treatment have been getting longer, the patients with different subtype of EGFR mutations exhibited diverse drug response to EGFR-TKIs. The reasons why are still unclear. In this study, we performed whole genome and panel sequencing of 239 spatially distinct regions from 42 lung adenocarcinoma of Chinese patients, of which 14 patients carried EGFR 19del mutation (EGFR-19Del), 15 patients carried L858R mutation (EGFR-L858R) and 13 patients did not carry any of these two mutation types (Control). We found the intra-tumor heterogeneity (ITH) levels were significantly higher in EGFR-mutant patients compared with control (P<0.05). Average fraction of nonubiquitous mutation was 93.63%, 93.87% and 71.34% in EGFR-19Del, EGFR-L858R and Control, respectively. Remarkably, mutational process preferentially associated with different genes on different pathways were observed between two EGFR mutant subtypes, in which cell cycle related pathways were more likely to mutate in EGFR-L858R patients, while cell adhesion associated pathways were more susceptible to mutations in EGFR-19Del patients. Furthermore, two distinct evolutionary patterns were identified in EGFR-mutant patients based on whether TP53 mutations occurred simultaneously. In EGFR-mutant patients with stage I, the prognosis of patients with TP53 mutations was significantly worse than those without TP53 mutations. Meanwhile, we found that in the absence of TP53 mutations, more than 70% of EGFR-L858R patients showed multiple recurrent clonal driver mutations regardless of the stage of the patients. In contrast, EGFR-19Del patients only carried recurrent clonal driver mutation of EGFR in stage I, and began to accumulate other clonal driver mutations in later stage, which may indicate different evolutionary strategies underlying these two subtypes. These preliminary results suggested that intratumor genetic diversity provided a substrate for tumor adaptation and evolution in the subtype of EGFR mutation. It could provide genetic basis for diagnosis and prognosis in EGFR-TKIs therapeutic response and to guide stratification of lung cancer treatment and clinical research in future. Citation Format: Sitan Qiao, Xin Zhao, Xinlan Zhou, Yaxiong Zhang, Li Zhang, Kui Wu. Intratumor heterogeneity of non-small-cell lung cancer with EGFR mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2906.

Clinical efficacy of video-assisted thoracoscopic lobectomy in the treatment of primary lung cancer in elderly patients

Objective To evaluate the clinical efficacy of video-assisted thoracoscopic lobectomy in the treatment of primary lung cancer in elderly patients. Methods Clinical data of 50 elderly patients with primary non-small cell lung cancer undergoing lobectomy at our hospital from July 2016 to July 2017 were retrospectively analyzed.The patients were divided into video-assisted thoracoscopic surgery(VATS)group(n=30)and conventional thoracotomy group(n=20). General data of surgery including operating time, intraoperative bleeding volume, the total volume of intraoperative drainage, the group number of lymph node dissection and the number of dissected lymph nodes, and postoperative data including duration of chest tube drainage, the first 24 h post-operative pain numeric rating scale(NRS)score, postoperative hospitalization time and 30-day postoperative complication were analyzed and compared between the two groups. Results All operations were successfully completed in all patients of both groups, and no patient died during the perioperative period.The differences were statistically significant between VATS and traditional thoracotomy groups in operating time[(96.8±10.2)min vs.(126.3±16.1)min, t=6.211, P=0.036], in transoperative bleeding[(101.3±12.7)ml vs.(128.3±14.6)ml, t=4.310, P=0.027]and in total volume of intraoperative draining[(231.7±31.6)ml vs.(295.6±39.8)ml, t=5.610, P=0.018]. VATS showed superiority over traditional thoracotomy.In VATS groups vs.the traditional thoracotomy group, the duration of chest tube drainage was[(3.0±0.6)d vs.(3.9±0.8)d, t=5.317, P=0.022], postoperative pain NRS score was[(3.61±1.09)vs.(5.3±1.3)score, t=6.290, P=0.016]and postoperative hospitalization time was[(5.9±1.6)d vs.(8.9±1.9)d, t=3.069, P=0.031]. In addition, the incidences of postoperative complications were lower in the VATS group than in the traditional thoracotomy group(1/30 or 3.3% vs.5/20 or 25.0%, χ2=5.335, P=0.021). Conclusions Video-assisted thoracoscopic lobectomy is safe and effective in treating primary lung cancer in elderly patients and can promote postoperative recovery, which is more suitable for elderly patients with primary lung cancer. Key words: Carcinoma, non-small-cell lung; Thoracoscopy; Pneumonectomy

Cerebral Thromboembolism after Lobectomy for Lung Cancer: Pathological Diagnosis and Mechanism of Thrombus Formation.

Lung cancer is the leading cause of cancer-related deaths worldwide. Although molecular therapies have emerged as efficacious strategies for the treatment of lung cancer, surgical resection is still recommended as a radical therapeutic option. Currently, lobectomy is regarded as the most reliable radical treatment of primary lung cancer. Among the various complications after lobectomy, cerebral thromboembolism requires attention as a life-threatening complication during the early postoperative period. It occurs in 0.2–1.2% of surgical cases of lung cancer and typically develops following left upper lobectomy with a long pulmonary vein stump (PVS). PVS-associated thrombosis is known to cause cerebral thromboembolism after such procedures; however, distinguishing this specific complication from that caused by postoperative atrial fibrillation is challenging. We summarize herein the diagnostic pathology of thrombus formation in accordance with its thrombogenic mechanism. We focus on the potential utility of the pathological assessment of thrombectomy specimens. The morphological information obtained from these specimens enables the presumption of thrombogenic etiology and provides useful clues to both select an appropriate pharmacotherapy and determine a follow-up treatment for cerebral thromboembolism.

Chinese guidelines for diagnosis and treatment of primary lung cancer 2018 (English version).

Chinese guidelines for diagnosis and treatment of primary lung cancer 2018 (English version).