An autopsy case of lung adenocarcinoma with immune checkpoint inhibitor-induced pneumonia and fulminant myocarditis following pembrolizumab administration: a case report.

Immune checkpoint inhibitors (ICIs) are the current standard of care for non-small-cell lung cancer (NSCLC). Myocarditis is a rare but serious immune-related adverse event (irAE) associated with ICI therapy. We present a patient who received a single dose of pembrolizumab for NSCLC and developed ICI-associated pneumonia. Although pneumonia improved with corticosteroid therapy, the patient subsequently developed ICI-associated fulminant myocarditis. Despite high-dose corticosteroid therapy, the patient died on day 30 after pembrolizumab initiation. Even if an observed irAE was effectively treated, clinicians should remain vigilant for other irAEs, especially those that are difficult to control with low-dose corticosteroids.

Supernatant fluid from endobronchial ultrasound-guided transbronchial needle aspiration for rapid next-generation sequencing.

INTRODUCTION: There is an increasing demand to optimize the workflow and maximize tissue available for next-generation sequencing (NGS) for non-small cell carcinoma. We looked at transbronchial needle endobronchial ultrasound-guided bronchoscopy with transbronchial needle aspiration samples and evaluated the performance of supernatant (SN) fluid processed from a dedicated aspirate collected for NGS testing. MATERIALS AND METHODS: Nineteen samples were collected and processed using a new workflow. Five aspirates were collected in formalin. One additional dedicated pass was collected fresh and centrifuged. The resulting cell pellet was added to formalin for cell block (CB) processing. DNA and RNA were extracted from concentrated SN for targeted testing using the Oncomine Precision Assay (Thermo Scientific, Waltham, MA). NGS results from the corresponding CB samples were used as "controls" for comparison. RESULTS: Thirty-one mutations were detected in SN (Table 1). The most frequently mutated genes were TP53 (35%), EGFR (23%), KRAS (13%), CTNNB1 (6%), and ERBB2 (6%). There was 100% concordance between the mutations detected in SN and corresponding CBs with comparable variant allele frequencies. Turnaround time of NGS results was 1 day for SN compared to 4-10 days for CB. CONCLUSIONS: We were able to demonstrate the usefulness of SN for reliable rapid molecular results. We successfully incorporated the workflow for tissue handling and processing among our clinical, cytopathology, and molecular teams. Molecular results were available at the same time as the cytologic diagnosis, allowing for timely reporting of a comprehensive diagnosis. This approach is particularly useful in patients with advanced disease requiring urgent management.

Soft tissue tumor of metastatic non-small cell lung carcinoma: A rare case report.

INTRODUCTION AND IMPORTANCE: It is estimated that 1 out of 5 patients with cancer will experience bone metastasis. With non-small cell lung cancer by itself having 220.000 reported cases per year, but the prevalence of soft tissue metastasis from lung cancer is only 2.3 % making it commonly overlooked as a possible metastasis site. CASE PRESENTATION: Male presents with a lump and pain on the right upper arm. A 8 cm × 8 cm mass was palpated under the biceps. CT-scan showed a lung lesion on the anterior segment. Shoulder MRI showed a dense, lobulated, and indefinitely demarcated soft tissue mass approximately 5.6 cm × 7.8 cm × 8.8 cm. The patient was treated with wide excision of the tumor. Core biopsy showed a metastatic adenosquamous carcinoma with suspected primary lesion from the respiratory tract. Treatment with targeted chemotherapy and radiotherapy were then done to the patient. The patient was discharged without any complications and is still at remission at the 6 months post-operative checkup. CLINICAL DISCUSSION: Soft tissue metastasis of lung cancer cell is a rare but a very real phenomenon. In our case the diagnosis of the soft tissue mass as a metastasis from the lungs was decided on a clinical, physical, radiological, and histological basis without using immunohistochemistry. CONCLUSION: MRI, biopsy, and immunohistochemistry are traditionally needed to confirm the diagnosis but in select cases, radiological and microscopic examinations along with clinical correlation are enough to ascertain the diagnosis. While it is rare, a soft tissue metastasis should always be suspected in lung cancer patients that have a palpable mass.

A Rare Case of Non-small Cell Lung Cancer With Skeletal Metastasis to the Sartorius Muscle.

We report an interesting case of skeletal muscle metastasis from lung cancer. Skeletal muscle metastasis is an unusual clinical occurrence and therefore lacks a standardized treatment approach. A 60-year-old female patient initially presented with abdominal pain and was found to have right lung consolidation, two hepatic lesions, and a lesion to the sartorius muscle. Initially treated as pneumonia, questions arose as to the lesion to the liver as well as the sartorius muscle. The primary site of malignancy was initially questioned due to the large size of the two hepatic lesions, with differential diagnoses including lung or hepatic origin. The sartorius muscle biopsy confirmed the presence of an adenocarcinoma lesion, consistent with non-small cell lung cancer (NSCLC).

FOXM1 promotes the progression of non-small cell lung cancer by inhibiting miR-509-5p expression via binding to the miR-509-5p promoter region.

Background: Forkhead box M1 (FOXM1) functions as a transcription factor and is consistently overexpressed in various cancers, including non-small-cell lung-, breast-, cervical-, and colorectal cancer. Its overexpression is associated with poor prognosis in patients with non-small-cell lung cancer, although the detailed mechanisms by which FOXM1 promotes the development of non-small-cell lung cancer remain unclear. Objective: The mechanism of FOXM1 in migration, invasion, apoptosis, and viability of lung cancer cells was investigated. Methods: Transwell assay, scratch test, and flow cytometry were employed to study the effects of FOXM1 on migration, invasion, and apoptosis in A549 cells. A quantitative polymerase chain reaction was used to determine the impact of FOXM1 on miR-509-5p expression in A549 cells. Dual-luciferase reporter gene assay and chromatin immunoprecipitation were adopted to investigate the molecular mechanisms of FOXM1 on miR-509-5p expression. Results: FDI-6 (a FOXM1 inhibitor) reduced the protein abundance of FOXM1, thereby increasing the expression of miR-509-5p in A549 cells. Moreover, FDI-6 treatment significantly reduced migration, invasion, and viability of A549 cells while promoting cell apoptosis. Furthermore, miR-509-5p inhibitor obviously alleviated the biological effects of FDI-6 on A549 cells, suggesting that FOXM1 primarily exerted its cancer promoting effect by regulating miR-509-5p. Mechanistically, FOXM1 directly bound to the miR-509-5p promoter to inhibit miR-509-5p expression. Conclusion: FOXM1 directly binds to the promoter region of miR-509-5p to form a negative feedback loop, thereby inhibiting miR-509-5p expression and promoting the development of non-small-cell lung cancer. This study is expected to complement research on the pathogenesis of non-small-cell lung cancer and promote the development of novel therapeutic targets for this disease.

ECG Changes Post-pericardiocentesis for Cardiac Tamponade Secondary to Non-small Cell Carcinoma of the Lung.

Electrical alternans on electrocardiograph (ECG) is an uncommon but nearly pathognomonic sign of cardiac tamponade. Here, we present a male quadragenarian who came to the emergency department complaining of low back and right upper abdominal pain. Work-up revealed a large pericardial effusion associated with electrical alternans on ECG and clinical findings of cardiac tamponade. Pericardiocentesis drained approximately 1 liter of hemorrhagic fluid with resolution of cardiac tamponade and normalization of the ECG. Further evaluation with right hilar lymph node biopsy confirmed a diagnosis of poorly differentiated non-small cell adenocarcinoma of the lung.

A rare case of squamous cell carcinoma within the necrotic mass of acute necrotizing pneumonia: when cancer strikes unpredictably.

Introduction and importance: This case report presents an intriguing instance of a 35-year-old nonsmoker female who exhibited a convergence of acute necrotizing pneumonia (ANP) and squamous cell carcinoma (SCC), two distinct pulmonary conditions. ANP involves severe lung infection and tissue necrosis, while SCC is a non-small cell lung carcinoma originating from the bronchial epithelium. Such a unique combination in a nonsmoker female patient emphasizes the intricate interplay of diverse pulmonary pathologies and the importance of comprehensive diagnostic evaluation and effective patient management strategies. Case presentation: The patient's symptoms include fever, pain, cough, and sporadic hemoptysis. Initial imaging suggested ANP due to a multilobulated necrotic lung mass. Despite empirical antibiotic therapy, no improvement occurred, prompting further investigation. Positron emission tomography and computed tomography revealed intense fluorodeoxyglucose avidity in the lesion. A computer tomography-guided Tru-cut biopsy confirmed non-small cell carcinoma with squamous differentiation in the necrotic mass. Clinical discussion: ANP is a severe manifestation of pneumonia, predominantly affecting young, healthy individuals, while SCC, commonly linked to smoking, presents as non-small cell lung carcinoma. Overlapping symptoms and radiological findings complicate diagnosis. Early diagnosis and appropriate management are crucial for both conditions to prevent progression and complications. Conclusion: This case highlights the significance of precise diagnosis and adaptable treatment approaches. The coexistence of ANP and SCC in a nonsmoker female patient underscores the necessity of meticulous diagnostic evaluation and personalized treatment strategies. The scarcity of such presentations emphasizes the need for further research to comprehend the mechanisms underlying these occurrences.

The First Cold Atmospheric Plasma Phase I Clinical Trial for the Treatment of Advanced Solid Tumors: A Novel Treatment Arm for Cancer.

Local regional recurrence (LRR) remains the primary cause of treatment failure in solid tumors despite advancements in cancer therapies. Canady Helios Cold Plasma (CHCP) is a novel Cold Atmospheric Plasma device that generates an Electromagnetic Field and Reactive Oxygen and Nitrogen Species to induce cancer cell death. In the first FDA-approved Phase I trial (March 2020-April 2021), 20 patients with stage IV or recurrent solid tumors underwent surgical resection combined with intra-operative CHCP treatment. Safety was the primary endpoint; secondary endpoints were non-LRR, survival, cancer cell death, and the preservation of surrounding healthy tissue. CHCP did not impact intraoperative physiological data (p > 0.05) or cause any related adverse events. Overall response rates at 26 months for R0 and R0 with microscopic positive margin (R0-MPM) patients were 69% (95% CI, 19-40%) and 100% (95% CI, 100-100.0%), respectively. Survival rates for R0 (n = 7), R0-MPM (n = 5), R1 (n = 6), and R2 (n = 2) patients at 28 months were 86%, 40%, 67%, and 0%, respectively. The cumulative overall survival rate was 24% at 31 months (n = 20, 95% CI, 5.3-100.0). CHCP treatment combined with surgery is safe, selective towards cancer, and demonstrates exceptional LRR control in R0 and R0-MPM patients. (Clinical Trials identifier: NCT04267575).

Histology-Validated Dielectric Characterisation of Lung Carcinoma Tissue for Microwave Thermal Ablation Applications.

Microwave thermal ablation is a promising emerging treatment for early-stage lung cancer. Applicator design optimisation and treatment planning rely on accurate knowledge of dielectric tissue properties. Limited dielectric data are available in the literature for human lung tissue and pulmonary tumours. In this work, neoplastic and non-neoplastic lung dielectric properties are characterised and correlated with gross and histological morphology. Fifty-six surgical specimens were obtained from twelve patients undergoing lung resection for lung cancer in University Hospital of Galway, Ireland. Dielectric spectroscopy in the microwave frequency range (500 MHz-8.5 GHz) was performed on the ex vivo lung specimens with the open-ended coaxial probe technique (in the Department of Pathology). Dielectric data were analysed and correlated with the tissue histology. The dielectric properties of twelve lung tumours (67% non-small cell carcinoma (NSCC)) and uninvolved lung parenchyma were obtained. The values obtained from the neoplastic lung specimens (relative permittivity: 52.0 ± 5.4, effective conductivity: 1.9 ± 0.2 S/m, at 2.45 GHz) were on average twice the value of the non-neoplastic lung specimens (relative permittivity: 28.3 ± 6.7, effective conductivity: 1.0 ± 0.3 S/m, at 2.45 GHz). Dense fibrosis was comparable with tumour tissue (relative permittivity 49.3 ± 4.6, effective conductivity: 1.8 ± 0.1 S/m, at 2.45 GHz).

Deep immune B and plasma cell repertoire in non-small cell lung cancer.

Introduction: B cells, which have long been thought to be minor players in the development of anti-tumor responses, have been implicated as key players in lung cancer pathogenesis and response to checkpoint blockade in patients with lung cancer. Enrichment of late-stage plasma and memory cells in the tumor microenvironment has been shown in lung cancer, with the plasma cell repertoire existing on a functional spectrum with suppressive phenotypes correlating with outcome. B cell dynamics may be influenced by the inflammatory microenvironment observed in smokers and between LUAD and LUSC. Methods: Here, we show through high-dimensional deep phenotyping using mass cytometry (CyTOF), next generation RNA sequencing and multispectral immunofluorescence imaging (VECTRA Polaris) that key differences exist in the B cell repertoire between tumor and circulation in paired specimens from lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC). Results: In addition to the current literature, this study provides insight into the in-depth description of the B cell contexture in Non-Small Cell Lung Cancer (NSCLC) with reference to broad clinico-pathological parameters based on our analysis of 56 patients. Our findings reinforce the phenomenon of B-cell trafficking from distant circulatory compartments into the tumour microenvironment (TME). The circulatory repertoire shows a predilection toward plasma and memory phenotypes in LUAD however no major differences exist between LUAD and LUSC at the level of the TME. B cell repertoire, amongst other factors, may be influenced by the inflammatory burden in the TME and circulation, that is, smokers and non-smokers. We have further clearly demonstrated that the plasma cell repertoire exists on a functional spectrum in lung cancer, and that the suppressive regulatory arm of this axis may play a significant role in determining postoperative outcomes as well as following checkpoint blockade. This will require further long-term functional correlation. Conclusion: B and Plasma cell repertoire is very diverse and heterogeneous across different tissue compartments in lung cancer. Smoking status associates with key differences in the immune milieu and the consequent inflammatory microenvironment is likely responsible for the functional and phenotypic spectrum we have seen in the plasma cell and B cell repertoire in this condition.

Nivolumab-Induced Organizing Pneumonia in Management of Non-small Cell Lung Carcinoma: A Case Report.

Nivolumab is an immune checkpoint inhibitor (ICI) that has proven efficacy in managing certain malignancies, including non-small lung carcinoma. In this case, we present a 53-year-old female patient diagnosed with metastatic non-small lung carcinoma. After management with radiation (both external beam and brachytherapy) and tumor debulking by bronchoscopic cryotherapy, she developed an initial pneumonitis attributed to nivolumab and ipilimumab. This was successfully managed with steroid therapy and allowed nivolumab monotherapy to restart. However, several months later, she developed organizing pneumonia, prompting immunotherapy discontinuation and initiation of corticosteroid therapy. This case serves as a reminder to clinicians that although ICIs constitute a novel, effective therapy for certain malignancies, immunological side effects can be debilitating and prevent continued immunotherapy. Through this case, we aim to review the literature about this rare side effect of nivolumab-induced pneumonitis, risk factors, diagnosis, and management.

A Challenging Case of Metastatic Non-Small Cell Carcinoma of the Lung.

Primary lung carcinoma with distant metastasis is a life-threatening diagnosis that presents many unique challenges due to the severity of the disease at the time of presentation. We investigated a life-threatening primary lung carcinoma with distant metastasis in a 73-year-old transgender woman, which posed unique challenges due to the advanced stage of the disease at presentation. The patient exhibited nonspecific musculoskeletal and neurological symptoms resulting from the primary lung carcinoma metastasizing to her liver, bones, and brain. We evaluated various imaging modalities that aided in determining the disease's severity and identifying complications related to metastasis. Although these efforts can offer symptomatic relief, the overall prognosis remains poor when metastasis spreads to multiple organs, particularly the brain, as remission may no longer be attainable.

Prediction model on disease recurrence for low risk resected stage I lung adenocarcinoma.

BACKGROUND AND OBJECTIVE: Although stage I non-small cell lung carcinoma (NSCLC) typically carries a good prognosis following complete resection, early disease recurrence can occur. An accurate survival prediction model would help refine a follow-up strategy and personalize future adjuvant therapy. We developed a post-operative prediction model based on readily available clinical information for patients with stage I adenocarcinoma. METHODS: We retrospectively studied the disease-free survival (DFS) of 408 patients with pathologically confirmed low-risk stage I adenocarcinoma of lung who underwent curative resection from 2013 to 2017. A tree-based method was employed to partition the cohort into subgroups with distinct DFS outcome and stepwise risk ratio. These covariates were included in multivariate analysis to build a scoring system to predict disease recurrence. The model was subsequently validated using a 2011-2012 cohort. RESULTS: Non-smoker status, stage IA disease, epidermal-growth factor receptor mutants and female gender were associated with better DFS. Multivariate analysis identified smoking status, disease stage and gender as factors necessary for the scoring system and yielded 3 distinct risk groups for DFS [99.4 (95% CI 78.3-125.3), 62.9 (95% CI 48.2-82.0), 33.7 (95% CI 24.6-46.1) months, p < 0.005]. External validation yielded an area under the curve by receiver operating characteristic analysis of 0.863 (95% CI 0.755-0.972). CONCLUSION: The model could categorize post-operative patients using readily available clinical information, and may help personalize a follow-up strategy and future adjuvant therapy.

The Effect of Pleural Effusion on Prognosis in Patients with Non-Small Cell Lung Cancer Undergoing Immunochemotherapy: A Retrospective Observational Study.

Objectives: Combined immune checkpoint inhibitor (ICI) therapy and chemotherapy has become the standard treatment for advanced non-small-cell lung cancer (NSCLC). Pleural effusion (PE) is associated with poor outcomes among patients with NSCLC undergoing chemotherapy. However, minimal data exists on PE for patients undergoing combined ICI and chemotherapy. Therefore, we investigated how PE affects survival outcomes in patients with NSCLC undergoing this combined therapy. Methods: We identified patients with advanced NSCLC undergoing chemotherapy and ICI therapy from the Okayama Lung Cancer Study Group−Immune Chemotherapy Database (OLCSG−ICD) between December 2018 and December 2020; the OLCSG−ICD includes the clinical data of patients with advanced NSCLC from 13 institutions. Then, we analyzed the treatment outcomes based on the presence of PE. Results: We identified 478 patients who underwent combined ICI therapy and chemotherapy; 357 patients did not have PE, and 121 patients did have PE. Patients with PE had significantly shorter progression-free survival (PFS) and overall survival (OS) than those without PE (median PFS: 6.2 months versus 9.1 months; p < 0.001; median OS: 16.4 months versus 27.7 months; p < 0.001). The negative effect of PE differed based on the patient's programmed cell death-ligand 1 (PD-L1) expression status; with the effect being more evident in patients with high PD-L1 expression. In addition, PFS and OS did not differ between patients who did and did not undergo bevacizumab treatment; thus, bevacizumab-containing regimens did not improve the survival outcomes for patients with PE. Conclusion: PE is associated with poor outcomes among patients with NSCLC undergoing combined ICI therapy and chemotherapy.

Neoadjuvant Therapy for Patients With Non-small Cell Lung Cancer Complicated With Chest Wall Invasion.

BACKGROUND/AIM: Multidisciplinary treatment including anatomical pulmonary and chest wall resection is recommended for lung cancer complicated by chest wall invasion. The present study aimed to investigate the survival benefit and safety of preoperative therapy followed by surgery for non-small cell lung cancer with chest wall invasion. PATIENTS AND METHODS: Sixty-five patients who underwent surgical excision of lung cancer complicated with chest wall invasion between 2009 and 2020 were enrolled in this study. RESULTS: The median age was 65 (37-81) years old, with 59 males and 6 females. Histological types included squamous cell carcinoma (n=32) and adenocarcinoma (n=21). The median tumor diameter was 5.5 cm (2.3-12.5 cm). The clinical nodal status was N0 in 49 cases and N positive in 16 cases. Of the 65 eligible patients, 5- and 10-year overall survival (OS) rates were 58.4% and 46.0%, respectively, and 5- and 10-year progression-free survival (PFS) rates were 54.2% and 41.7%, respectively. For patients receiving preoperative therapy followed by surgery (Pre-Tx), 5- and 10-year OS survival rates were 69.2% and 62.9%, and among patients receiving up-front surgery (UFS) were 48.5% and 29.1%, respectively (p=0.03). The 5- and 10-year PFS rates for pre-Tx were 65.8% and 59.2%, respectively, and 44.7% and 26.8% for UFS, respectively (p=0.02). Cox regression analysis preoperative therapy was significantly associated with OS and PFS. CONCLUSION: We demonstrate the survival benefit of preoperative therapy followed by surgery for patients with lung cancer and chest wall invasion.

Open-label, multi-center, phase II study of adjuvant pemetrexed plus cisplatin for completely resected stage IB to IIIA adenocarcinoma of the lung: APICAL trial.

Background: We aimed to evaluate the efficacy of postoperative adjuvant pemetrexed plus cisplatin (Pem-Cis) in pathologic stage IB-IIIA lung adenocarcinoma (LUAD) patients. Methods: A prospective, phase II study was performed in seven institutions in South Korea. Patients with completely resected stage IB-IIIA LUAD received pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2). Adjuvant treatments were administered every 3 weeks for 4 cycles. The primary endpoint was to prove the Pem-Cis's superiority in terms of 2-year disease-free survival rate (DFSR) compared with historical control without adjuvant chemotherapy (50%). Results: Between August 2015 and February 2018, 105 patients were enrolled in this study. Approximately 31.4% (n=33), 43.8% (n=46), and 24.8% (n=26) of patients had pathologic stage IB, II, and IIIA, respectively. Most of the patients underwent lobectomy (n=98, 93.3%). Moreover, 41.1% and 12.1% of the patients had epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase rearrangement. Four cycles of Pem-Cis were administered in 99 patients (94.3%). At a median follow-up of 57.7 months, the 2-year DFSR was 78.1%. Multivariable analysis showed that pathologic stage IIIA and EGFR mutation were significant risk factors for DFS. Grade 3 adverse events occurred in 10 patients (9.5%), and leukopenia (n=3, 2.9%) was the most common adverse event. Conclusions: Adjuvant Pem-Cis is superior to historical control without adjuvant treatment in terms of 2-year DFSR; the proportion of patients with stage IB and driver mutations were higher than that of patients in previous trials. Pem-Cis showed favorable tolerability as adjuvant chemotherapy (clinicaltrial.gov; Identifier: NCT02498860).

A Prospective Validation Study of Lung Cancer Gene Panel Testing Using Cytological Specimens.

Background: Genetic panel tests require sufficient tissue samples, and therefore, cannot always be performed. Although collecting cytological specimens is easier than tissue collection, there are no validation studies on the diagnostic accuracy of lung cancer gene panel tests using cytology samples. Methods: Using an amplicon-based high-sensitivity next-generation sequencing panel test capable of measuring eight druggable genes, we prospectively enrolled consecutive patients who underwent diagnostic procedures. We evaluated the analysis accuracy rate, nucleic acid yield, and the quality of cytological specimens under brushing, needle aspiration, and pleural effusion. We then compared these specimens with collected tissue samples. Results: In 163 prospectively enrolled cases, nucleic acid extraction and analysis accuracy was 100% in cases diagnosed with adenocarcinoma. Gene mutations were found in 68.7% of cases with 99.5% (95% CI: 98.2-99.9) concordance to companion diagnostics. The median DNA/RNA yield and DNA/RNA integrity number were 475/321 ng and 7.9/5.7, respectively. The correlation coefficient of the gene allele ratio in 64 cases compared with tissue samples was 0.711. Conclusion: The success of gene analysis using cytological specimens was high, and the yield and quality of the extracted nucleic acid were sufficient for panel analysis. Moreover, the allele frequency of gene mutations in cytological specimens showed high correlations with tissue specimens.

Effective response to crizotinib of concurrent KIF5B-MET and MET-CDR2-rearranged non-small cell lung cancer: A case report.

BACKGROUND: Due to the rarity of mesenchymal-epithelial transition factor (MET) fusions, the clinical efficacy of crizotinib has only been described in a few patients with MET fusions involving various fusion partners. Herein, we report the clinical response to crizotinib of a patient with advanced poorly differentiated non-small cell carcinoma (NSCLC) having concurrent MET fusions. CASE SUMMARY: A 46-year-old woman was diagnosed with poorly differentiated NSCLC (T4N3M1). With no classic driver mutations, she was treated with two cycles of gemcitabine and cisplatin without clinical benefit. Targeted sequencing revealed the detection of two concurrent MET fusions, KIF5B-MET and novel MET-CDR2. Crizotinib was initiated at a dose of 250 mg twice daily. Within 4 wk of crizotinib therapy, repeat computed chromatography revealed a dramatic reduction in primary and metastatic lesions, assessed as partial response. She continued to benefit from crizotinib for 3 mo until disease progression and died within 1 mo despite receiving nivolumab therapy. CONCLUSION: Crizotinib sensitivity was observed in an advanced poorly differentiated NSCLC patient with concurrent MET fusions KIF5B-MET and MET-CDR2. Crizotinib can serve as a therapeutic option for patients with MET fusions. In addition, our case also highlights the importance of comprehensive genomic profiling particularly in patients with no classic driver mutation for guiding alternative therapeutic decisions.

Baseline PD-L1 expression and tumour-infiltrated lymphocyte status predict the efficacy of durvalumab consolidation therapy after chemoradiotherapy in unresectable locally advanced patients with non-small-cell lung cancer.

BACKGROUND: Chemoradiotherapy (CRT) followed by durvalumab treatment improved prognosis in unresectable locally advanced non-small-cell lung cancer (LA-NSCLC). This study aimed to evaluate whether the status of the immune-related tumour microenvironment (TME) at baseline associates with the efficacy. METHODS: This retrospective study evaluated immune-related TME factors, including programmed cell death ligand 1 (PD-L1) (clone: 22C3) expression on tumour cells and the density of CD8-positive tumour-infiltrating lymphocytes (TILs) at pre-CRT in patients with unresectable LA-NSCLC treated with CRT only (CRT alone group) and those treated with CRT followed by durvalumab (Durva group). RESULTS: A total of 551 patients were included (N = 113 in the Durva group). Progression-free survival (PFS) in the Durva group was significantly greater than that in the CRT alone group (not reached [NR] vs 12.9 months; p = 0.002). In the CRT alone group, neither PD-L1 expression nor TIL status affected PFS; in contrast, in the Durva group, high density of CD8-positive TILs (TILHigh ≥100/mm2) and PD-L1-positive expression (tumour proportion score ≥1%; PD-L1+) was significantly associated with longer PFS (TIL: NR vs 9.5 months; p = 0.002; and PD-L1: NR vs 7.7 months; p = 0.003). On the other hand, in patients with epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangements, there was no significant difference in PFS between the groups (Durva vs CRT alone: 9.9 months vs 14.0 months; p = 0.77). CONCLUSIONS: PD-L1+ and TILHigh at baseline could be predictive markers of the efficacy of CRT followed by durvalumab.

Prognostic impact of tumor-infiltrating lymphocytes in non-small cell lung carcinomas.

INTRODUCTION: Tumor-infiltrating lymphocytes represent a pivotal component of the host anti-tumor response. Thus, they considerably influence the evolution of cancers including non-small cell lung carcinomas. Even if, this important role is consensual, many discordant results are published in the literature about the prognostic role of the different populations of tumor-infiltrating lymphocytes. The aim of our work was to evaluate the prognostic impact of CD8+, CD4+, and forkhead box protein P3+ lymphocytes in the tumor microenvironment of non-small cell lung carcinomas. METHODS: We conducted a retrospective descriptive study, which included non-small cell lung carcinomas diagnosed in the department of pathology and followed in the medical oncology department of the same hospital between 2011 and 2015. Tumor-infiltrating lymphocytes were analyzed by the immunohistochemical method for forkhead box protein P3, CD4, and CD8. Intratumoral and stromal-labeled lymphocytes were quantified by manual counting at high magnification (×400). Forkhead box protein P3+/CD8+, forkhead box protein P3+/CD4+, and CD8+/CD4+ ratios were subsequently calculated. The prognostic value of tumor-infiltrating lymphocytes was assessed in respect of overall survival, recurrence-free survival, and relapse-free survival. RESULTS: Thirty-nine patients were included. The mean age of patients was 59.6 years. A complete surgical resection (p = 0.009), and a CD8/CD4 ratio (p = 0.008) were prognostic factors for overall survival. Complete surgical resection (p = 0.003), the forkhead box protein P3/CD8 (p = 0.005), and forkhead box protein P3/CD4 (p = 0.037) ratios were prognostic factors for recurrence-free survival. The CD8+ tumor-infiltrating lymphocytes rate (p = 0.037) was a prognostic factor for relapse-free survival with a threshold of 67.8/high power field. Microscopic subtype (p = 0.037) was a prognostic factor for relapse-free survival when only adenocarcinoma and squamous cell carcinoma were considered. In multivariate analysis, age (p = 0.004) and a CD8/CD4 ratio (p = 0.016) were independent predictors of overall survival. CONCLUSION: Despite the limitations of our study, our results confirm the prognostic value of tumor-infiltrating lymphocytes in non-small cell lung carcinomas and the importance of the combined quantification of their different subpopulations.