BACKGROUND: Lung cancer is one of the commonest cause of cancer associated mortality worldwide. Platelets have emerged as key players in cancer development and progression by supporting tumor growth, and dissemination. In the present systematic review, we analyzed RNA transfer between cancer cells and platelets and explored potential role of different platelet RNA profiles as onco-signature in diagnosis, subtyping, disease progression and treatment monitoring in carcinoma lung carcinoma.
METHODS: The study followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Cochrane Manual of Systematic Reviews and Meta-analysis that included seven studies on patients with lung cancer, with data on tumor-educated platelets, and control group. The outcome measured was based on sensitivity, specificity, and ROC. PUBMED, SCOPUS, Central Cochrane Registry of Controlled Trials and Science Direct databases were searched using specific search terms until October 2023. QUADAS - 2 tool was used to assess quality, risk of bias and applicability concerns.
RESULTS: The analysis revealed AUC > 70% for different platelet mRNAs, with sensitivity and specificity of more than 60 %. AUC and sensitivity were highest for ITGA2B (AUC 0.922; sensitivity 92.8%). lncRNA GTF2H2-1 was the most specific platelet RNA. On QUADAS-2 tool, 3/7 articles were unclear in reference standards, patient flow timing, and 1/7 had high bias in both aspects. For applicability, 1/7 studies were unclear in reference standards, and 2/7 in index tests.
CONCLUSIONS: TEP RNA can aid in early diagnosis of lung cancer and of proven utility in its early-stage detection. TEP RNA can also monitor disease progression and treatment response.

Non-small cell lung cancer metastasis to skeletal muscle is an uncommon occurrence. Lung cancers are more likely to spread to the brain, bone, liver, and adrenals. Here, we present a rare case of non-small cell lung cancer metastasis to the skeletal muscle in a 54-year-old male. In addition, we present a literature review on skeletal metastasis of non-small cell lung cancer. The most frequent presentation of skeletal muscle metastasis is muscular pain with or without swelling. The mechanism of metastasis to muscle is not well understood; it is theorized that hematogenous spread is the most likely route. As with our patient, the presence of skeletal muscle mass is considered an aggressive disease with poor survival, usually less than one year. The treatment for muscle metastasis is often palliative in the form of radiation therapy, chemotherapy, or surgical removal of the mass.

Immune-checkpoint inhibitors (IO) have significantly improved outcomes of patients with non-oncogene-addicted non-small cell lung cancer (NSCLC), becoming the first-line agents for advanced disease. However, resistance remains a significant clinical challenge, limiting their effectiveness.
Hereby, we addressed standard and innovative therapeutic approaches for NSCLC patients experiencing progression after IO treatment, discussing the emerging resistance mechanisms and the ongoing efforts to overcome them. In order to provide a complete overview of the matter, we performed a comprehensive literature search across prominent databases, including PubMed, EMBASE (Excerpta Medica dataBASE), and the Cochrane Library, and a research of the main ongoing studies on clinicaltrials.gov.
The dynamics of progression to IO, especially in terms of time to treatment failure and burden of progressive disease, should guide the best subsequent management, together with patient clinical conditions. Long-responders to IO might benefit from continuation of IO beyond-progression, in combination with other treatments. Patients who experience early progression should be treated with salvage CT in case of preserved clinical conditions. Finally, patients who respond to IO for a considerable timeframe and who later present oligo-progression could be treated with a multimodal approach in order to maximize the benefit of immunotherapy.

Lung cancer has the highest mortality of all cancers in the United States. The incidence of lung cancer with metastases to the skin varies between 1-12%, with the highest incidence seen in men. Here, we present two cases of lung cancer presenting as skin metastasis. The first patient was an 80-year-old African American male who presented to the hospital for evaluation of a right upper back mass. A few months prior to admission, he was found to have a left lung mass on CT scan of the chest, he underwent biopsy which showed poorly differentiated SCC of the lung. He also had a skin biopsy which showed poorly differentiated carcinoma in the dermis consistent with metastatic SCC. He was started on chemotherapy, but could not tolerate it. He was accepted to hospice. The second patient was a 78-year-old Hispanic female who presented to the hospital with dyspnea, and a dry cough. Upon physical examination, a 2 × 2 cm ulcerated, wart-like nodule on the right palm was noted. Subsequent CT scan of the chest showed a partial collapse of the right middle lobe. A biopsy of the hand mass revealed well-to-moderately differentiated metastatic SCC favoring lung origin. A bronchoscopy biopsy showed invasive SCC. Subsequently her condition worsened and she passed away. Metastasis to the skin is an unusual presenting symptom of lung cancer. It is therefore essential to consider metastasis as a diagnosis in a patient with both a skin lesion and a smoking history.

Advanced imaging techniques allow functional information to be derived and integrated into treatment planning.
A systematic review was conducted with the primary objective to evaluate the ability of functional lung imaging to predict risk of radiation pneumonitis. Secondary objectives were to evaluate dose-response relationships on post treatment functional imaging and assess the utility in including functional lung information into treatment planning. A structured search for publications was performed following PRISMA guidelines and registered on PROSPERO.
814 articles were screened against review criteria and 114 publications met criteria. Methods of identifying functional lung included using CT, MRI, SPECT and PET to image ventilation or perfusion. Six studies compared differences between functional and anatomical lung imaging at predicting radiation pneumonitis. These found higher predictive values using functional lung imaging. Twenty-one studies identified a dose-response relationship on post-treatment functional lung imaging. Nineteen planning studies demonstrated the ability of functional lung optimised planning techniques to spare regions of functional lung. Meta-analysis of these studies found that mean (95% CI) functional volume receiving 20 Gy was reduced by 4.2% [95% CI: 2.3: 6.0] and mean lung dose by 2.2 Gy [95% CI: 1.2: 3.3] when plans were optimised to spare functional lung. There was significant variation between publications in the definition of functional lung.
Functional lung imaging may have potential utility in radiation therapy planning and delivery, although significant heterogeneity was identified in approaches and reporting. Recommendations have been made based on the available evidence for future functional lung trials.

Clinicopathologic and molecular characteristics of non-small-cell lung cancers (NSCLCs) associated with a strong expression of programmed death ligand 1 (PD-L1+ in > 5% of cells) have not been well elucidated. Expression of PD-L1 is a poor prognostic factor, but NSCLCs with higher levels of PD-L1 have greater benefit when treated with immunotherapy. We have performed a systematic review to synthesize the available evidence regarding clinicopathologic and molecular variables associated with PD-L1 expression in NSCLC. PubMed, EMBASE, SCOPUS, Web of Science and Cochrane Library databases were searched for relevant articles assessing predictors of PD-L1 expression in > 5% cells. Data were reported as odds ratio (OR) of events. Fifty-two studies (for a total of 5066 PD-L1+ out of 13,279 NSCLC patients) were included in this meta-analysis. Factors associated with PD-L1 expression were: smoking status (OR 5.48; 95% confidence interval (CI) 2.8-10.4; P < .001), male gender (OR 4.8; 95% CI 3.2-7.2; P < .001), adenocarcinoma histology (OR 2.75; 95% CI, 1.5-4.8; P < .001), Epidermal growth factor receptor (EGFR) wild type (OR 4.83; 95% CI, 2.1-11.1; P < .001), ALK mutation negative (OR 388.6; 95% CI, 222.5-678.7; P < .001), ROS mutation negative (OR 1904.8; 95% CI, 630-5757; P < .001), and KRAS wild type (OR 19.8; 95% CI, 7.6-51.6; P < .001). Conversely higher pT stages (OR 0.16; 95% CI, 0.04-0.7; P = .01), pN+ stages (OR 0.29; 95% CI, 0.17-0.5; P < .001) are inversely associated with PD-L1 expression in > 5% cells. Expression of PD-L1 is more common in male smokers, with adenocarcinoma histology and not carriers of EGFR/ALK/ROS/KRAS mutations. These data could be useful to screening of PD-L1 expression and to select patients for immunotherapy.

Association of SIADH with malignancy was first reported in 1957, when it was described in two patients with bronchogenic carcinoma. While the association with small cell lung cancer (SCLC) is well known, that with non small cell lung cancer (NSCLC) has been rarely reported. We report a case of 70 year old male who was found to have hyponatremia secondary to SIADH. Radiological tests revealed right hilar lung mass with mediastinal adenopathy. Bronchoscopic biopsy revealed non-small cell lung cancer of type squamous cell. Magnetic resonance imaging (MRI) of brain showed metastatic lesions, thereby confirming diagnosis of metastatic lung cancer. Paraneoplastic syndromes occur in 10% of lung cancer cases and they represent a group of disorders related to secretion of functional polypeptides or hormones from tumor cells. SIADH is more commonly described in conjunction with small cell lung cancer but there are a few case reports describing it\'s occurrence after initiation of therapy for NSCLC such as radiation and chemotherapy. The mechanism for this phenomenon is not known. Unlike infectious causes, hyponatremia as initial presentation is an uncommon feature of malignancy-associated SIADH. In the lung cancer population, hyponatremia has been identified as a negative prognostic factor in hospitalized patients and those with advanced-stage disease. Malignancy should be a consideration in the diagnostic evaluation of SIADH, irrespective of the time of presentation.

Brain metastasis is the leading cause of death among advanced non-small cell lung cancer (NSCLC) and breast cancer patients. The standard treatment for brain metastases is radiotherapy. The combination of radiotherapy and chemotherapy has been tested. However, the management of brain metastases has yet to be successful. Here, we aimed to determine the efficacy and safety of whole brain radiotherapy (WBRT) alone or in combination with temozolomide (TMZ) in NSCLC and breast cancer patients with brain metastases. A systematic review of PubMed, CNKI (China National Knowledge Infrastructure) and WANFANG (WANGFANG data) involving 870 patients were conducted. Fourteen randomized controlled trials (RCTs) were independently identified by two reviewers. The primary outcome measures were objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and toxicity. The ORR was better with combination therapy of WBRT and TMZ than with WBRT alone (RR = 1.34, p < 0.00001) and subgroup analysis showed a significantly superior ORR in NSCLC patients (RR = 1.38, p < 0.00001), but not in breast cancer patients (RR = 1.03, p = 0.86). OS and PFS did not significantly differ between combination therapy and WBRT alone. A higher rate of toxicity was observed in combination therapy than in WBRT alone (RR = 1.83, p = 0.0006). No advantages of concurrent WBRT and TMZ were observed in breast cancer patients with brain metastases. Combination therapy was associated with improved ORR in NSCLC patients, especially in Chinese patients. As a \"surrogate endpoint\" for OS, ORR may allow a conclusion to be made about the management of NSCLC with brain metastases with the combination of WBRT and TMZ. However, it needs to be validated to show that improved ORR predicts the treatment effects on the clinical benefit. The ORR may be valid for a particular indication such as status of MGMT promoter methylation.

Fei-Liu-Ping ointment has been widely applied as adjunctive drug in the treatment of non-small cell lung cancer (NSCLC). However, there has been no systematic review of research findings regarding the efficacy of this treatment. Here, we provide a protocol for assessing the effectiveness and safety of Fei-Liu-Ping ointment in the treatment of NSCLC.
The electronic databases to be searched will include MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, Excerpt Medica Database (EMBASE), China National Knowledge Infrastructure (CNKI), China Scientific Journal Database (VIP), Wanfang Database and Chinese Biomedical Literature Database (CBM). Papers in English or Chinese published from inception to 2016 will be included without any restrictions. We will conduct a meta-analysis of randomised controlled trial if possible. The therapeutic effects according to the standard for treatment of solid tumours by the WHO and the quality of life as evaluated by Karnofsky score and weight will be applied as the primary outcomes. We will also evaluate the data synthesis and risk of bias using Review Manager 5.3 software.
The results of this review will offer implications for the use of Fei-Liu-Ping ointment as an adjunctive treatment for NSCLC. This knowledge will inform recommendations by surgeons and researchers who are interested in the treatment of NSCLC. The results of this systematic review will be disseminated through presentation at a conference and publication of the data in a peer-reviewed journal.
PROSPERO CRD42016036911.

Erlotinib is one of the most widely used tyrosine kinase inhibitor targeting human epidermal growth factor receptor. Since its introduction, it has revolutionized the treatment of advanced non-small cell lung cancer. Skin rashes and diarrhea are the most often reported side effects of erlotinib however it is also associated with interstitial pneumonitis or interstitial lung disease, which often turns out to be fatal complication of using this medicine. Though reported scarcely in the western world, the association of interstitial lung disease with epidermal growth factor receptor has attracted a lot of attention in the recent times. Various researches working with murine models of bleomycin-induced pulmonary fibrosis have found a pro and con role of the receptor in development of the interstitial lung disease. We present the case of a patient diagnosed with stage IV adenocarcinoma of the lung with metastasis to brain. He was found to be positive for the human epidermal growth factor mutation and was hence started on erlotinib. Within a few weeks of starting the medicine the patient was admitted with diarrhea. During the course of this admission he developed acute shortness of breath diagnosed as interstitial pneumonitis. The purpose of this case report is to review the literature associated with erlotinib induced interstitial pneumonitis and make the practicing oncologists aware of this rare yet fatal complication of erlotinib. Here we will also review literature, pertaining to the role of epidermal growth factor receptor in development of interstitial lung disease.