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.

BACKGROUND: Lung cancer is the world\'s leading cause of cancer deaths, and diagnosis remains challenging. Lung cancer starts as small nodules; early and accurate diagnosis allows timely surgical resection of malignant nodules while avoiding unnecessary surgery in patients with benign nodules.
OBJECTIVE: The Cole relaxation frequency (CRF) is a derived electrical bioimpedance signature, which may be utilized to distinguish cancerous tissues from normal tissues.
METHODS: Human testing ex vivo was conducted with NoduleScan in freshly resected lung tissue from 30 volunteer patients undergoing resection for nonsmall cell lung cancer. The CRF of the tumor and the distant normal lung tissue relative to the tumor were compared to histopathology specimens to establish a potential algorithm for point-of-care diagnosis. For animal testing in vivo, 20 mice were implanted with xenograft human lung cancer tumor cells injected subcutaneously into the right flank of each mouse. Spectral impedance measurements were taken on the tumors on live animals transcutaneously and on the tumors after euthanasia. These CRF measurements were compared to healthy mouse lung tissue. For porcine lung testing ex vivo, porcine lungs were received with the trachea. After removal of the vocal box, a ventilator was attached to pressurize the lung and simulate breathing. At different locations of the lobes, the lung\'s surface was cut to produce a pocket that could accommodate tumors obtained from in vivo animal testing. The tumors were placed in the subsurface of the lung, and the electrode was placed on top of the lung surface directly over the tumor but with lung tissue between the tumor and the electrode. Spectral impedance measurements were taken when the lungs were in the deflated state, inflated state, and also during the inflation-deflation process to simulate breathing.
RESULTS: Among 60 specimens evaluated in 30 patients, NoduleScan allowed ready discrimination in patients with clear separation of CRF in tumor and distant normal tissue with a high degree of sensitivity (97%) and specificity (87%). In the 25 xenograft small animal model specimens measured, the CRF aligns with the separation observed in the human in vivo measurements. The CRF was successfully measured of tumors implanted into ex vivo porcine lungs, and CRF measurements aligned with previous tests for pressurized and unpressurized lungs.
CONCLUSIONS: As previously shown in breast tissue, CRF in the range of 1kHz-10MHz was able to distinguish nonsmall cell lung cancer versus normal tissue. Further, as evidenced by in vivo small animal studies, perfused tumors have the same CRF signature as shown in breast tissue and human ex vivo testing. Inflation and deflation of the lung have no effect on the CRF signature. With additional development, CRF derived from spectral impedance measurements may permit point-of-care diagnosis guiding surgical resection.

Sweet syndrome is an uncommon inflammatory disorder characterized by the abrupt appearance of painful, erythematous papules, plaques, or nodules on the skin. Fever and leukocytosis frequently accompany the cutaneous lesions. In addition, involvement of the eyes, musculoskeletal system, and internal organs may occur. Sweet syndrome has been associated with a broad range of disorders. There are three subtypes: classical Sweet syndrome, malignancy-associated Sweet syndrome, and drug-induced Sweet syndrome. Classical Sweet syndrome is not associated with malignancy or drugs. It is essentially associated with an upper respiratory infection, gastrointestinal infection, inflammatory bowel disease, and pregnancy. Malignancy-associated Sweet syndrome is associated with hematologic malignancy more than solid malignancy, most commonly with acute myeloid leukemia. Drug-induced Sweet syndrome usually develops approximately two weeks after drug exposure, in patients who lack a prior history of exposure to the inciting drug. Here we are discussing our patient, a 68-year-old male who presented eight weeks after starting chemotherapy with pemetrexed, carboplatin, and pembrolizumab for left lung adenocarcinoma with macular rash. On further investigation with biopsy was found to have neutrophilic dermatitis, hence being diagnosed with drug-induced Sweet syndrome. Histopathology revealed a dermis with infiltration of neutrophils with lekocytoclasia.

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.

Lung cancer is the most common neoplastic disorder associated with paraneoplastic syndromes. The most common paraneoplastic syndromes are the syndrome of inappropriate release of antidiuretic hormone (SIADH), hypercalcemia of malignancy, ectopic Cushing\'s syndrome, and various other neurological syndromes. A few case reports have reported gynecomastia as a paraneoplastic syndrome. Recognition of this uncommon presentation can aid in the early detection of associated malignancies, thus potentially improving outcomes. In this article, we are presenting the case of a male patient in his late sixties who, on presentation, had gynecomastia and was eventually diagnosed with non-small-cell lung cancer (NSCLC).

The lung\'s sarcomatoid carcinomas (SC) are a heterogeneous sporadic group of non-small cell lung carcinomas (NSCLCs) and are very challenging to diagnose and treat. Spindle cell carcinoma (SpCC) is a very rare subset of this group. Hence, the prognosis and treatments are unclear due to the limited literature available. The presentation of this cancer varies based on the site of the neoplasm and the complications and metastases observed at the time of diagnosis. Here, we report a 73-year-old man who presented to the emergency room after two months of worsening dyspnea and fatigue. Chest X-ray showed an extensive left-sided pleural effusion. A computed tomography (CT) scan of the chest showed a pleural-based mass that came back as SpCC, for which he was referred to a university hospital.

Lung adenocarcinoma, the predominant subtype of non-small cell lung cancer, typically metastasizes to common sites such as the liver and adrenal glands. However, rare instances involve skeletal muscle metastasis. We present a case of a 45-year-old female with a medical history of hypertension, epilepsy, and fibromyalgia, who presented to the emergency department with hemoptysis and multifocal pain. Chest imaging revealed a cavitary lesion which appeared to be necrotizing pneumonia. Further investigations uncovered a fluid collection in the left thigh, which would be identified as poorly differentiated carcinoma. Subsequent testing identified the lung as the primary source of metastasis. Despite radiation treatment, the patient\'s condition deteriorated over the next 50 days, highlighting the aggressive nature of the disease.

OBJECTIVE: Aim of this study is to identify the factors that may influence the lymphadenectomy during VATS anatomical lung resection with particular interest on operator experience.
METHODS: Clinical and pathological data from the prospective VATS Italian nationwide registry were reviewed and analysed. Patients with incomplete data regarding tumor and surgical characteristics, GGO, or with distant metastases were excluded. Patients clinical data, tumor characteristics, operation information and surgeon experience were collected and compared to resected lymph nodes number (#RN), resected N2 nodes number (#N2RN) and resected N2 stations number. A multivariable model was built using logistic regression analysis. Surgeon experience was categorized considering the number of VATS major anatomical resection and years after residency.
RESULTS: The final analysis was conducted on 3727 patients. The median #RN and #N2RN were 11 (1-51) and 5 (0-41). Regarding the analysed outcomes, #N2RN > 6 resulted in 1812 (48.8%)cases, #RN > 10 in 2124 (57.0%)cases and more than 3 N2 stations were harvested in 1447 (38.8%)patients. First operator experience with number of VATS lobectomies>50 (p < 0.001), operator seniority after residency5-10years (p < 0.001), cTNM II/III(p = 0.017), lobectomy/bilobectomy vs segmentectomy (p < 0.001), and upper/middle lobe tumor location (p < 0.005)resulted significantly associated to #N2RN > 6 at the multivariable analysis. First operator experience with number of VATS lobectomies>50 (p < 0.001), operator seniority after residency5-10years (p < 0.001) and lobectomy/bilobectomy (p < 0.001) resulted significantly associated to #RN > 10 at the multivariable analysis.
CONCLUSIONS: Our study showed that lymphadenectomy during VATS lobectomy is influenced by tumor factors such as cTstage and tumor location but also by operator experience, with a higher number of resected lymph nodes in surgeons with a high number of VATS procedures and years after residency compared to surgeons with less experience.

BACKGROUND: The prognosis of metastatic non-small cell lung cancer (NSCLC) has been improved by the use of immune checkpoint inhibitors (ICI). Unfortunately, in some cases, cancer cells will develop resistance mechanisms. In case of progression in a limited number of lesions (oligoprogression), focal treatment with radiotherapy is proposed while continuing the ICI therapy.
METHODS: A cohort of 37 patients with metastatic NSCLC treated with nivolumab (anti-PD-1) in second or subsequent line and who received focal radiotherapy for oligoprogression with continuation of nivolumab was compared with a control cohort of 87 patients no oligoprogressor treated par immunotherapy.
RESULTS: After a median follow-up of 37 months [18; 62], the median progression free survival (PFS) in the radiotherapy-treated cohort was 15.04 versus 5.04 months in the control cohort, with a statistically significant difference (P=0.048). The median PFS following focal radiotherapy in the oligoprogressor group was 7.5 months. In univariate analysis, the presence of lung metastasis was associated with increased PFS, in contrast to the presence of brain metastases, which were associated with decreased PFS in the radiotherapy group. The median overall survival was not reached in both groups, with no significant difference between the two cohorts.
CONCLUSIONS: The combination of focal radiotherapy in case of oligoprogression and continued treatment with nivolumab in the treatment of metastatic NSCLC in the second or subsequent line of treatment seems to be with an increase in PFS.

BACKGROUND: In patients with advanced NSCLC (aNSCLC), the impact of KRAS mutations (m) and comutations with STK11 and KEAP1 on outcomes across different PD-L1 levels remains incompletely understood. We aimed to investigate the frequency of KRAS mutations and comutations across PD-L1 levels, and the association between these mutations and survival, stratified by PD-L1 expression.
METHODS: We conducted a nationwide cohort study of patients diagnosed with aNSCLC between 2016 and 2021 treated with frontline (chemo)immunotherapy, who underwent molecular genotyping including KRAS, STK11, and KEAP1. Real-world overall survival (OS) and progression-free survival (rwPFS) were estimated using Kaplan-Meier methodology. Cox multivariable regressions were used to evaluate the association between KRASm and survival across different PD-L1 strata, and to assess whether the association between KRASm and survival differed by PD-L1 level. Finally, within subgroups defined by PD-L1 expression, we used interaction terms to assess whether co-mutations with STK11 and KEAP1 moderated the association between KRAS mutation and survival.
RESULTS: Of our 2593-patient cohort, 982 (37.9 %) were KRASm and 1611 (62.1 %) KRASwt. KRASm were enriched in the PD-L1 ≥50 % cohort (334/743, 45 %), but within patients with KRASm, co-mutations with STK11 and KEAP1 were enriched in the PD-L1 0 % cohort. KRASm was associated with significantly worse OS in the PD-L1 0 % cohort compared to the PD-L1 ≥50 % cohort (P for interaction = 0.008). On adjusted analyses stratified by PD-L1, KRASm was associated with worse survival only in the PD-L1 0 % group (OS HR 1.46, p = 0.001). KEAP1 and STK11 comutations were most strongly associated with worse OS in the PD-L1 0 % subgroup; patients with triple KRASm/KEAPm/STK11m PD-L1 0 % NSCLC experienced the worst outcomes.
CONCLUSIONS: KRASm are associated with worse overall survival in PD-L1 negative NSCLC; however, this association is largely driven by comutations with STK11 and KEAP1, which are enriched in PD-L1 negative tumors.