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Abstract Background The standard care for resectable non-small cell lung cancer (NSCLC) involves perioperative therapy combining chemotherapy and immune checkpoint inhibitors, typically lasting 6 to 12 months. However, the optimal treatment strategies for potentially resectable squamous cell lung carcinoma (SCC) remain unclear. This Phase 2 trial aimed to assess the efficacy and safety of a condensed four-cycle perioperative treatment regimen with tislelizumab combined with chemotherapy in patients with potentially resectable stage III SCC. Methods Patients with potentially resectable stage IIIA-IIIB (N2) SCC received intravenous tislelizumab, albumin-bound paclitaxel, and carboplatin for up to four cycles. The primary endpoints were major pathologic response (MPR) and incidence of treatment-related adverse events. Safety and potential biomarkers for efficacy prediction were also assessed. Results Among 35 enrolled patients, 32 underwent surgery with R0 resection achieved in all cases. MPR was achieved in 24 patients and pathological complete response (pCR) in 14 patients. Radiographic objective response was observed in 31 patients. The 12-month and 24-month event-free survival rate was 85.7 and 61.0%, respectively. Four patients experienced grade 3 or 4 adverse events. Tumor tissue based next-generation sequencing revealed the potential associations between several biomarkers and pathological response, including tumor neoantigen burden score, 18-gene expression profile score, CD8 + T cells, M1/M2 macrophages ratio and interferon‐gamma expression level. Besides, circulating tumor DNA (ctDNA) dynamics and concentration were also associated with pathological response and the presence of ctDNA at postoperative month 1 was a strong predictor for disease relapse. Furthermore, metagenomic sequencing in bronchoalveolar lavage fluid demonstrated Streptococcus was the most abundant genus in the pCR group. Conclusions A condensed four-cycle perioperative treatment regimen of tislelizumab combined with chemotherapy demonstrated promising efficacy and manageable toxicities in potentially resectable stage III SCC. Specific biomarkers showed potential for predicting treatment efficacy and the mechanism of superior antitumor response of pCR patients was preliminarily and indirectly explored. Trial registration ClinicalTrials.gov, NCT05024266. Registered August 27, 2021.

Background: The standard care for resectable non-small cell lung cancer (NSCLC) involves perioperative therapy combining chemotherapy and immune checkpoint inhibitors, typically lasting 6 to 12 months. However, the optimal treatment strategies for potentially resectable squamous cell lung carcinoma (SCC) remain unclear. This Phase 2 trial aimed to assess the efficacy and safety of a condensed four-cycle perioperative treatment regimen with tislelizumab combined with chemotherapy in patients with potentially resectable stage III SCC. Methods: Patients with potentially resectable stage IIIA-IIIB (N2) SCC received intravenous tislelizumab, albumin-bound paclitaxel, and carboplatin for up to four cycles. The primary endpoints were major pathologic response (MPR) and incidence of treatment-related adverse events. Safety and potential biomarkers for efficacy prediction were also assessed. Results: Among 35 enrolled patients, 32 underwent surgery with R0 resection achieved in all cases. MPR was achieved in 24 patients and pathological complete response (pCR) in 14 patients. Radiographic objective response was observed in 31 patients. The 12-month and 24-month event-free survival rate was 85.7 and 61.0%, respectively. Four patients experienced grade 3 or 4 adverse events. Tumor tissue based next-generation sequencing revealed the potential associations between several biomarkers and pathological response, including tumor neoantigen burden score, 18-gene expression profile score, CD8 + T cells, M1/M2 macrophages ratio and interferon‐gamma expression level. Besides, circulating tumor DNA (ctDNA) dynamics and concentration were also associated with pathological response and the presence of ctDNA at postoperative month 1 was a strong predictor for disease relapse. Furthermore, metagenomic sequencing in bronchoalveolar lavage fluid demonstrated Streptococcus was the most abundant genus in the pCR group. Conclusions: A condensed four-cycle perioperative treatment regimen of tislelizumab combined with chemotherapy demonstrated promising efficacy and manageable toxicities in potentially resectable stage III SCC. Specific biomarkers showed potential for predicting treatment efficacy and the mechanism of superior antitumor response of pCR patients was preliminarily and indirectly explored. Trial registration: ClinicalTrials.gov, NCT05024266. Registered August 27, 2021. [ABSTRACT FROM AUTHOR]

Lung cancer remains the leading cause of cancer-related mortality, with 1.8 million deaths per year. Small cell lung cancer and non-small cell lung cancer (NSCLC) are the main cancer types. Approximately 85% of cases are NSCLC, including adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. In this reported treatment case, the tumor histological type changed after targeted therapy, which has not been previously well documented. The patient was a 67-year-old woman diagnosed with squamous cell carcinoma via bronchoscopy. She received five neoadjuvant immune monotherapies. The lesion shrank but then progressed, with a diagnosis of small cell carcinoma via bronchoscopy. This finding suggests that tumor acquisition of resistance as manifested by cancer-type changes needs consideration and study in the application of this particular type of immunotherapy. [ABSTRACT FROM AUTHOR]

Purpose: Retinoic acid inducible protein 3 (RAI3) has been suggested as prognostic biomarker in several cancer types. The present study aimed to examine the role of RAI3 expression in non-small cell lung cancers (NSCLCs). Methods: RAI3 protein expression was evaluated by immunohistochemistry in tissue microarray (TMA) sections from a retrospective cohort of more than 600 surgically resected NSCLCs and results were compared with clinicopathological features and follow-up data. Results: While membranous RAI3 immunostaining was always strong in benign lung, strong RAI3 staining was only detectable in 14.7% of 530 interpretable NSCLCs. Within NSCLC subtypes, immunostaining intensity for RAI3 was significantly decreased in large cell lung cancers (LCLCs) and squamous cell carcinomas (SQCCs) relative to lung adenocarcinomas (LUACs) (P < 0.0001 each). However, RAI3 staining was neither associated with pathological features of NSCLCs nor with survival of patients (P = 0.6915). Conclusion: Our study shows that RAI3 expression was not associated with clinical outcomes of NSCLC patients and cannot be considered as prognostic marker in lung cancer patients. [ABSTRACT FROM AUTHOR]

Synchronous multiple primary lung cancers are separate tumors presenting at the same time with different histology. We present a rare case of a 64-year-old patient with a combination of small-cell lung carcinoma (SCLC) and squamous carcinoma in two different sites with metastasis of SCLC in the mediastinal lymph node. The SCLC diagnosis was performed via bronchoscopy, and the other diagnosis via CT-guided transthoracic biopsy. It is often difficult to distinguish a synchronous tumor from intrapulmonary metastases. To date, there are no guidelines for the treatment of these cases. The management of synchronous multiple primary lung cancer (SMPLC), mainly surgical with chemotherapy or radiotherapy, must be studied according to the histological type, staging and molecular testing of the tumors. These rare cases of SMPLC require individual treatment and a multidisciplinary approach.

Abstract Background Bullous pemphigoid is an uncommon dermatologic manifestation seen in squamous cell lung cancer, and evidence guiding optimal treatment, especially in the elderly population, is limited. We report herein a case of squamous cell lung cancer diagnosed after being investigated for refractory bullous pemphigoid showing marked response to carboplatin-based chemotherapy. This is the first case report that shows carboplatin can be used as an effective alternative in treatment of malignancy-associated bullous pemphigoid. Case report An 80-year-old caucasian man developed extensive vesiculobullous rashes on his trunk, chest, abdomen, and inguinal region associated with significant pruritus causing sleep disturbance. The diagnosis of bullous pemphigoid was confirmed on skin biopsy. The skin lesions continued to worsen even after use of oral and topical steroid in addition to oral doxycycline. Chest computed tomography revealed a spiculated left lung lesion along with mediastinal lymphadenopathy. Fine-needle aspiration from the mediastinal lymph node confirmed metastatic squamous cell lung carcinoma. Carboplatin with gemcitabine was initiated, and significant response was seen within 3 days of chemotherapy. The skin lesions continued to remain in remission even after stopping the chemotherapy. Conclusion Although there are still controversies regarding paraneoplastic etiology of bullous pemphigoid, this case presents a temporal association. It is the first case report showing a remarkable response with the use of a carboplatin-based regimen.

The aim of the present study was to investigate the efficacy and safety of anlotinib combined with vinorelbine (NVB) as a second-line treatment for elderly patients with advanced squamous cell lung carcinoma (SqCLC). The present retrospective analysis included 48 elderly patients (aged ≥65 years) diagnosed with advanced SqCLC who received anlotinib in combination with NVB as a second-line therapy between January 2021 and December 2023. The primary endpoints assessed were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and safety profile. The median PFS and OS for the cohort was found to be 5.0 and 9.5 months, respectively. By contrast, the ORR and DCR were found to be 29.17 and 70.83%. Further subgroup analysis indicated that patients who experienced specific adverse events (AEs), such as hypertension, proteinuria and hand-foot syndrome during treatment, generally had superior efficacy compared with those who did not experience these AEs (mPFS, 6.0 vs. 4.0 months; mOS, 11.0 vs. 8.5 months). In addition, apart from promising efficacy, patients who experienced common AEs also experienced decreased appetite (35.42%), fatigue (29.17%), hypertension (25%) and hand-foot syndrome (27.08%). Grade 3 or higher AEs occurred in <30% of patients, the majority of which was alleviated through corresponding support care. These results suggest that the combination of anlotinib and NVB as second-line therapy for elderly patients with advanced SqCLC demonstrated promising efficacy and a manageable safety profile. Such regimen may be a viable treatment option for this patient population. However, further prospective studies are required to validate these findings and optimize the dosing schedule for improved therapeutic outcomes., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2025 Li et al.)

Brain radiation necrosis is a serious adverse effect of radiotherapy in patients with malignant brain metastases. There is currently no standard treatment for brain radiation necrosis; however, there are advantages to using bevacizumab. Nonetheless, due to the risk of severe bleeding when bevacizumab is used in patients with squamous cell lung carcinoma, relevant clinical studies are lacking; therefore, there is no clear conclusion on the use of bevacizumab to treat brain radiation necrosis in patients with squamous cell carcinoma of the lung with brain metastases. The present study described the case of a patient treated with bevacizumab after brain radiation injury with pathological manifestations diagnosed as squamous cell carcinoma of the lung. Through the evaluation of clinical symptoms and imaging data, the patient was diagnosed with cerebral radiation necrosis a few months after receiving local radiotherapy for intracranial metastatic lesions. After four cycles of treatment with bevacizumab (7.5 mg/kg once every 3 weeks, intravenous drip), the clinical and imaging manifestations of the patient were considerably improved with no significant adverse effects. The favorable efficacy and safety profiles of this patient suggest that bevacizumab holds potential as a future therapeutic option for managing radiation-induced brain necrosis in patients with squamous cell lung cancer., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Gan et al.)

Cystic hepatic metastasis of squamous cell carcinoma usually develops from necrosis due to insufficient blood supply, yet metastasis initially resembling simple liver cyst is rare. Here, we present a case of a patient with squamous cell lung carcinoma history who found an isolated cystic mass in the liver. Historical MR studies indicated that the mass did not exist 12 months ago and emerged as a small cystic lesion 7 months ago. Radiological findings and tumor markers level suggested metastasis, while 18F-Fluorodeoxyglucose (18F-FDG) PET/CT showed moderate tracer uptakes in solid parts of the mass. Pathological study after surgery confirmed metastatic squamous cell carcinoma. Chemotherapy plus recombinant human endostatin and sintilimab therapy was employed after surgery; however, the patient developed remote metastasis of osteolytic lesions in the humerus bone and thoracic vertebra. Our case indicates that metastasis should be taken into consideration in emerging cystic hepatic lesion with malignant history. [ABSTRACT FROM AUTHOR]

Background: Recent findings indicate that the host microbiome can have a significant impact on the development of lung cancer by inducing an inflammatory response, causing dysbiosis, and generating genome damage. The aim of this study was to search for bacterial communities specifically associated with squamous cell carcinoma (LUSC). Methods: In this study, the taxonomic composition of the sputum microbiome of 40 men with untreated LUSC was compared with that of 40 healthy controls. Next-Generation sequencing of bacterial 16S rRNA genes was used to determine the taxonomic composition of the respiratory microbiome. Results: There were no differences in alpha diversity between the LUSC and control groups. Meanwhile, differences in the structure of bacterial communities (β diversity) among patients and controls differed significantly in sputum samples (pseudo-F = 1.53; p = 0.005). Genera of Streptococcus, Bacillus, Gemella, and Haemophilus were found to be significantly enriched in patients with LUSC compared to the control subjects, while 19 bacterial genera were significantly reduced, indicating a decrease in beta diversity in the microbiome of patients with LUSC. Conclusions: Among other candidates, Streptococcus (Streptococcus agalactiae) emerges as the most likely LUSC biomarker, but more research is needed to confirm this assumption. [ABSTRACT FROM AUTHOR]

Lung squamous cell carcinoma (LUSC) is the second most common histopathological subtype of lung cancer, and smoking is the leading cause of this type of cancer. However, the critical factors that directly affect the survival rate and sensitivity to immunotherapy of smoking LUSC patients are still unknown. Previous studies have highlighted the role of N6-methyladenosine (m6A) RNA modification, the most common epigenetic modification in eukaryotic species, together with immune-related long non-coding RNAs (lncRNAs) in promoting the development and progression of tumors. Thus, elucidating m6A-modified immune lncRNAs in LUSC patients with smoking history is vital. In this study, we described the expression and mutation features of the 24 m6A-related regulators in the smoking-associated LUSC cohort from The Cancer Genome Atlas (TCGA) database. Then, two distinct subtypes based on the expression levels of the prognostic m6A-regulated immune lncRNAs were defined, and differentially expressed genes (DEGs) between the subtypes were identified. The distributions of clinical characteristics and the tumor microenvironment (TME) between clusters were analyzed. Finally, we established a lncRNA-associated risk model and exhaustively clarified the clinical features, prognosis, immune landscape, and drug sensitivity on the basis of this scoring system. Our findings give insight into potential mechanisms of LUSC tumorigenesis and development and provide new ideas in offering LUSC patients with individual and effective immunotherapies. [ABSTRACT FROM AUTHOR]

Abstract Background In the treatment of lung cancer, the presence or absence of mediastinal lymph node involvement has a significant bearing on the indication for surgery. In addition, if a tumor is found in the trachea during preoperative scrutiny of lung cancer, the possibility of intratracheal metastasis should be considered, since this kind of metastasis is a contraindication for surgery. In the present study, we experienced a case of lung cancer associated with pneumoconiosis and a rare intratracheal leiomyoma. In this case, preoperative staging was difficult, but endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and intratracheal tumor biopsy were helpful in determining the treatment strategy. Case presentation A 65-year-old man was referred to our hospital for evaluation of abnormal chest X-ray shadows. Sputum cytology indicated squamous cell carcinoma. PET-CT scan showed fluorodeoxyglucose uptake in a right upper lobe mass and the hilar, mediastinal and right supraclavicular lymph nodes, and bronchoscopy revealed a protuberant lesion in the left bronchus. Hence, EBUS-TBNA for the mediastinal lymph nodes and simultaneous evaluation of the protuberant lesion in the left bronchus were performed. The bronchial tumor was histopathologically diagnosed as leiomyoma. Since mediastinal lymph node biopsy showed no malignant cells, a right upper lobectomy and a right S6 segmentectomy were performed. Postoperative pathological evaluation of the dissected lymph nodes revealed pneumoconiosis but no metastasis. He was, thus, diagnosed with squamous cell lung carcinoma (pT2bN0M0, pStage IIA). Conclusions We report a patient with lung cancer and coexistence of a rare endobronchial leiomyoma and pneumoconiosis, who underwent surgery after preoperative evaluation using EBUS-TBNA.

The aim of the present study was to investigate the efficacy and safety of anlotinib combined with vinorelbine (NVB) as a second-line treatment for elderly patients with advanced squamous cell lung carcinoma (SqCLC). The present retrospective analysis included 48 elderly patients (aged ≥65 years) diagnosed with advanced SqCLC who received anlotinib in combination with NVB as a second-line therapy between January 2021 and December 2023. The primary endpoints assessed were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and safety profile. The median PFS and OS for the cohort was found to be 5.0 and 9.5 months, respectively. By contrast, the ORR and DCR were found to be 29.17 and 70.83%. Further subgroup analysis indicated that patients who experienced specific adverse events (AEs), such as hypertension, proteinuria and hand-foot syndrome during treatment, generally had superior efficacy compared with those who did not experience these AEs (mPFS, 6.0 vs. 4.0 months; mOS, 11.0 vs. 8.5 months). In addition, apart from promising efficacy, patients who experienced common AEs also experienced decreased appetite (35.42%), fatigue (29.17%), hypertension (25%) and hand-foot syndrome (27.08%). Grade 3 or higher AEs occurred in <30% of patients, the majority of which was alleviated through corresponding support care. These results suggest that the combination of anlotinib and NVB as second-line therapy for elderly patients with advanced SqCLC demonstrated promising efficacy and a manageable safety profile. Such regimen may be a viable treatment option for this patient population. However, further prospective studies are required to validate these findings and optimize the dosing schedule for improved therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Brain radiation necrosis is a serious adverse effect of radiotherapy in patients with malignant brain metastases. There is currently no standard treatment for brain radiation necrosis; however, there are advantages to using bevacizumab. Nonetheless, due to the risk of severe bleeding when bevacizumab is used in patients with squamous cell lung carcinoma, relevant clinical studies are lacking; therefore, there is no clear conclusion on the use of bevacizumab to treat brain radiation necrosis in patients with squamous cell carcinoma of the lung with brain metastases. The present study described the case of a patient treated with bevacizumab after brain radiation injury with pathological manifestations diagnosed as squamous cell carcinoma of the lung. Through the evaluation of clinical symptoms and imaging data, the patient was diagnosed with cerebral radiation necrosis a few months after receiving local radiotherapy for intracranial metastatic lesions. After four cycles of treatment with bevacizumab (7.5 mg/kg once every 3 weeks, intravenous drip), the clinical and imaging manifestations of the patient were considerably improved with no significant adverse effects. The favorable efficacy and safety profiles of this patient suggest that bevacizumab holds potential as a future therapeutic option for managing radiation-induced brain necrosis in patients with squamous cell lung cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung cancer is the most prevalent malignant neoplasm worldwide. Pulmonary squamous cell carcinoma (SCC) is a histological subtype of non-small cell lung carcinoma with a high rate of morbimortality. The identification of biomarkers with prognosis value is critical in the follow-up and management of SCC patients. Amplification of Epidermal Growth Factor Receptor (EGFR) gen on 7p12 is frequently found in pulmonary SCC. We analyzed this alteration with immunohistochemistry, and fluorescence in situ hybridization, along with clinic-pathological variables such as gender, age, pT-stage, lymph node status, pleural invasion, stage, recurrence, metastasis, and overall survival, in a homogeneous population of 108 patients. We found that EGFR amplification, exclusively in early stage SCC (pT1–pT2), is an independent adverse prognostic factor for overall survival and combined with visceral pleural invasion, allows the identification of three groups of pulmonary SCC patients with significantly different outcome, which could be established at diagnosis. Over the last few decades, an increasing amount of information has been accumulated on biomarkers in non-small cell lung cancer (NSCLC). Despite these advances, most biomarkers have been identified in the adenocarcinoma histological subtype (AC). However, the application of molecular-targeted therapies in the prognosis and treatment of SCC in the clinical setting is very limited, becoming one of the main focus areas in research. Here, we prospectively analyzed the frequency of numerical/structural abnormalities of chromosomes 5, 7, 8, 9, 13 and 22 with FISH in 48 pulmonary SCC patients. From a total of 12 probes, only abnormalities of the 7p12 and 22q12 chromosomal regions were identified as unique genetic variables associated with the prognosis of the disease. The study for these two chromosomal regions was extended to 108 patients with SCC. Overall, chromosome losses were observed more frequently than chromosome gains, i.e., 61% versus 19% of all the chromosome abnormalities detected. The highest levels of genetic amplification were detected for the 5p15.2, 7p12, 8q24 and 22q11 chromosome bands, of which several genes are potentially involved in the pathogenesis of SCC, among others, include the EGFR gene at chromosome 7p12. Patients who displayed EGFR amplification (n = 13; 12%) were mostly older than 65 years (p = 0.07) and exclusively patients in early T-primary tumor stage (pT1–pT2; p = 0.03) with a significantly shortened overall survival (OS) (p ≤ 0.001). Regarding prognosis, the clinical, biological, and histopathologic characteristics of the disease that displayed a significant adverse influence on OS in the univariate analysis included patients older than 65 years (p = 0.02), the presence of lymph node involvement (p = 0.005), metastasis (p = 0.01) and, visceral pleural invasion (VPI) at diagnosis (p = 0.04). EGFR amplification also conferred an adverse impact on patient OS in the whole series (p = 0.02) and especially in patients in early stages (pT1–pT2; p = 0.01). A multivariate analysis of the prognostic factors for OS showed that the most informative combination of independent variables to predict an adverse outcome was the presence of VPI and/or EGFR amplification (p < 0.001). Based on these two variables, a scoring system was built to stratify patients into low- (no adverse features: score 0; n = 69), intermediate- (one adverse feature: score 1; n = 29) and high-risk (two adverse features: score 2; n = 5) groups, with significantly different (p = 0.001) OS rates at 50 months, which were as following: 32%, 28% and 0%, respectively. In the present study, we show that the presence of a high level of 7p12 (EGFR) amplification, exclusively detected in early stage SCC (pT1–pT2), is an independent adverse prognostic factor for OS. The identification of the EGFR gene copy number using FISH techniques may provide a more accurate diagnosis of high-risk populations after the complete resection of the primary tumor. When combined with VPI, three groups of pulmonary SCC were clearly identified that show the extent of the disease. This is of such importance that further prospective studies are necessary in larger series of SCC patients to be classified at the time of diagnosis. This could be achieved with the combined assessment of 7p12 amplification and VPI in primary tumor samples. [ABSTRACT FROM AUTHOR]

Background: In the treatment of lung cancer, the presence or absence of mediastinal lymph node involvement has a significant bearing on the indication for surgery. In addition, if a tumor is found in the trachea during preoperative scrutiny of lung cancer, the possibility of intratracheal metastasis should be considered, since this kind of metastasis is a contraindication for surgery. In the present study, we experienced a case of lung cancer associated with pneumoconiosis and a rare intratracheal leiomyoma. In this case, preoperative staging was difficult, but endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and intratracheal tumor biopsy were helpful in determining the treatment strategy.Case Presentation: A 65-year-old man was referred to our hospital for evaluation of abnormal chest X-ray shadows. Sputum cytology indicated squamous cell carcinoma. PET-CT scan showed fluorodeoxyglucose uptake in a right upper lobe mass and the hilar, mediastinal and right supraclavicular lymph nodes, and bronchoscopy revealed a protuberant lesion in the left bronchus. Hence, EBUS-TBNA for the mediastinal lymph nodes and simultaneous evaluation of the protuberant lesion in the left bronchus were performed. The bronchial tumor was histopathologically diagnosed as leiomyoma. Since mediastinal lymph node biopsy showed no malignant cells, a right upper lobectomy and a right S6 segmentectomy were performed. Postoperative pathological evaluation of the dissected lymph nodes revealed pneumoconiosis but no metastasis. He was, thus, diagnosed with squamous cell lung carcinoma (pT2bN0M0, pStage IIA).Conclusions: We report a patient with lung cancer and coexistence of a rare endobronchial leiomyoma and pneumoconiosis, who underwent surgery after preoperative evaluation using EBUS-TBNA. [ABSTRACT FROM AUTHOR]

Clinical trials indicated that PD-1/PD-L1 inhibitors significantly improve the survival rate of patients with advanced non-small cell lung cancer (NSCLC) and induce immune-related adverse events (irAEs). Thus, the molecular and immune characteristics during PD-1/PD-L1 inhibitor therapy are worth investigating further. We report the case of a 62-year-old male patient diagnosed with stage IIIA squamous cell lung carcinoma (SQCC) who responded to neoadjuvant and adjuvant nivolumab combined chemotherapy but died from anastomosis leakage or/and irAEs. In the pretreatment tumor biopsy, PD-L1 expression was negative and a few T cells, NK cells, and macrophages had infiltrated the tumor. Wild-type EGFR/STK11, mutant TP53, microsatellite stability, and low tumor mutational burden were also found at baseline. After neoadjuvant immunochemotherapy, the tumor was significantly reduced, PD-L1 expression levels were increased by 50%, and more CD8+ and CD8+ PD-1+ T cells had infiltrated the resected tumor tissue. Immune-related lung injury occurred during adjuvant immunochemotherapy, and serum levels of C-reactive protein, IL-13, IL-4, eotaxin, VEGF-A, IL-8, and IFN-gamma were increased. This case demonstrates a squamous cell lung carcinoma patient who responded to neoadjuvant immunochemotherapy that reshaped the tumor immune environment from “cold” to “hot.” Unfortunately, the patient eventually died from anastomosis leakage or/and irAEs during adjuvant immunochemotherapy.

Background: LUX-Lung 8 was a randomised, controlled, phase 3 study comparing afatinib and erlotinib as second-line treatment of patients with advanced squamous cell carcinoma (SCC) of the lung. We report the final overall survival (OS) and safety analyses of LUX-Lung 8 and investigate the characteristics of patients who achieved long-term benefit (≥12 months’ treatment). Methods: LUX-Lung 8 (NCT01523587) enroled patients between March 2012 and January 2014 and this final analysis had a data cut-off of March 2018. Eligible patients had stage IIIB or IV lung SCC and had progressed after at least four cycles of platinum-based chemotherapy. Patients were randomly assigned (1:1) to receive afatinib (40 mg per day) or erlotinib (150 mg per day) until disease progression. Endpoints included OS and safety; a post-hoc analysis of patients with long-term benefit (≥12 months on treatment) was also conducted. Findings: 795 eligible patients were randomly assigned (398 to afatinib, 397 to erlotinib). OS was significantly prolonged with afatinib compared with erlotinib (median 7·8 months vs 6·8 months; hazard ratio 0·84; 95% CI 0·73–0·97; p = 0·0193). These findings were consistent with those of the primary analysis and were consistent across subgroups. Adverse events (AEs) were manageable with dose interruption and reduction, with similar AEs being experienced between both groups. Twenty-one (5·3%) patients receiving afatinib and 13 (3·3%) patients receiving erlotinib achieved long-term benefit; median OS was 34·6 months and 20·1 months, respectively. Amongst 132 afatinib-treated patients who underwent tumour genetic analysis, ERBB family mutations were more common in patients with long-term benefit than in the overall population (50% vs 21%). Interpretation: Afatinib is a treatment option for patients with SCC of the lung progressing on chemotherapy who are ineligible for immunotherapy, particularly those with ERBB family genetic aberrations. Afatinib has a predictable and manageable tolerability profile, and long-term treatment may be well tolerated. Funding: Boehringer Ingelheim.

Clinical trials indicated that PD-1/PD-L1 inhibitors significantly improve the survival rate of patients with advanced non-small cell lung cancer (NSCLC) and induce immune-related adverse events (irAEs). Thus, the molecular and immune characteristics during PD-1/PD-L1 inhibitor therapy are worth investigating further. We report the case of a 62-year-old male patient diagnosed with stage IIIA squamous cell lung carcinoma (SQCC) who responded to neoadjuvant and adjuvant nivolumab combined chemotherapy but died from anastomosis leakage or/and irAEs. In the pretreatment tumor biopsy, PD-L1 expression was negative and a few T cells, NK cells, and macrophages had infiltrated the tumor. Wild-type EGFR / STK11 , mutant TP53 , microsatellite stability, and low tumor mutational burden were also found at baseline. After neoadjuvant immunochemotherapy, the tumor was significantly reduced, PD-L1 expression levels were increased by 50%, and more CD8+ and CD8+ PD-1+ T cells had infiltrated the resected tumor tissue. Immune-related lung injury occurred during adjuvant immunochemotherapy, and serum levels of C-reactive protein, IL-13, IL-4, eotaxin, VEGF-A, IL-8, and IFN-gamma were increased. This case demonstrates a squamous cell lung carcinoma patient who responded to neoadjuvant immunochemotherapy that reshaped the tumor immune environment from "cold" to "hot." Unfortunately, the patient eventually died from anastomosis leakage or/and irAEs during adjuvant immunochemotherapy. [ABSTRACT FROM AUTHOR]

Objective To analyze iron death related genes and construct prognosis model of lung squamous cell carcinoma by Biological information method. Methods The transcriptome and clinical data of lung squamous cell carcinoma from the Cancer Ge-nome Atals(TCGA) database was downloaded. Searched for iron death-related genes from the existing literature, use R software to screen iron death-related genes related to prognosis, and then use LASSO regression analysis to screen key iron death-related genes, and construct a prognostic model. According to the LASSO regression coefficient, the risk score of each patient was calculated and the patients were divided into high-risk group and low-risk group. Kaplan-Meier survival analysis and subject acceptance characteristic (receiver operating characteristic. ROC) curve were used to evaluate the model. The differential genes in the high-risk group and the low-risk group were analyzed, and the enrichment analysis and immune function status analysis of the differential genes were carried out. Finally, multivariate Cox regression was used to determine whether the prognostic model was a prognostic factor independent of other clinical features. Results Univariate Cox regression analysis showed that among the 52 differentially ex pressed genes related to iron death, 5 genes may be related to prognosis and these 5 genes were also confirmed as key genes affecting prognosis by LASSO regression analysis. In addition, the results of the survival analysis showed that the low-risk group had a better prognosis than the high-risk group (Median survival was 1. 65 years in the high-risk group and 2. 26 years in the low-risk group, P<0,001). The ROC curve showed that the area under the 3-year survival rate was 0, 635 and the area under the 5-year survival rate was 0.619 The differential genes between high-risk group and low-risk group were mainly enriched in immune-related pathways and there were differences in immune function between the two groups, Multivariate Cox regression analysis showed that the prognostic model could be used as an independent prognostic factor (HR=2.893,95%CI=1. 687-3. 379 P<0. 05). Conclusion Through bioinformatics analysis, this study successfully established a prognosis model of lung squamous cell carcinoma based on five iron death-related genes. The model can successfully evaluate the individual prognosis and analyze the immune status of patients. It may provide a basis for individualized treatment of lung squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Case: Acrometastasis is extremely rare, accounting for 0.1% of all skeletal metastases. Metastases to the carpus are rarer still. This condition can be the first manifestation of an occult malignancy and generally indicates advanced disease. We present the case of a 53-year-old woman with acrometastasis of squamous cell lung cancer to the trapezium as the initial presentation of her malignancy. Conclusion: The presentation of acrometastasis can mimic infectious or inflammatory processes, leading to an erroneous diagnosis. Although exceptionally uncommon, it is important to consider as a differential diagnosis for a destructive hand lesion. [ABSTRACT FROM AUTHOR]

Background: The most effective method and length of time for administering adjuvant immunotherapy after surgery for non-small cell lung cancer (NSCLC) are still unknown. Various clinical trials have utilized diverse strategies for adjuvant treatment. In this case, we explore the potential benefits of neoadjuvant immunotherapy combined with chemotherapy in managing locally advanced lung squamous carcinoma, which often poses challenges for treatment. This multimodal approach aims to downstage tumors and optimize surgical outcomes., Case Description: Following a diagnosis of stage IIIB lung cancer, the patient underwent three cycles of neoadjuvant therapy using sintilimab, Abraxane, and Lobaplatin, resulting in a significant 45% reduction in tumor size. Subsequently, a right lower lobe lobectomy and systematic lymphadenectomy were performed using a uniportal video-assisted thoracic surgery (VATS) approach. Postoperative analysis revealed negative lymph nodes, with only a 5-mm residual tumor in the tumor bed, downstaging the cancer to IA1. Remarkably, the patient experienced a smooth recovery without any postoperative complications. One cycle of adjuvant therapy was administered following the operation to further support the patient's recovery and minimize the risk of disease recurrence. This comprehensive treatment approach underscores the importance of neoadjuvant therapy in optimizing surgical outcomes and improving long-term prognosis for patients with locally advanced lung cancer., Conclusions: For patients with stage III locally advanced lung squamous carcinoma, the combination of Sintilimab and Platinum-based drugs can be used as a neoadjuvant therapy which can reduce the difficulty of the operation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-522/coif). H.S. receives payment for lectures from MSD, Boehringer Ingelheim, ETHICON, Covidien, Chugai-pharm, Astellas Pharma, FUJIFILM Medical, Bristol-Myers Squibb, Takeda, AstraZeneca, CSL Behring, and TAIHO. The other authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Background Squamous cell lung carcinoma (LUSC) was closely associated with smoking which was known to have a distant immunosuppression effect. In this study, we aimed to explore the relationship between immune cells and clinical outcomes of LUSC patients with smoking history. Methods The immune cell infiltration and RNA expression profiles of LUSC patients were collected from The Cancer Genome Atlas (TCGA). Then, the correlation between immune cell infiltration and clinical characteristics was explored. According to the level of immune cell infiltration, LUSC patients with smoking history were divided into high or low group to screen the differentially expressed lncRNAs and mRNAs. The prediction of target genes was performed by miRanda. Finally, the prognostic value of a certain signature was confirmed in an independent dataset. Results Higher abundance of tumor-infiltrating T follicular helper (Tfh) cells together with a lower abundance of resting memory CD4 T cells had been found in LUSC current reformed smokers for ≤15 years and current smoking patients. Moreover, Tfh cell infiltration was not only associated with better overall survival (OS) but also varied from different degrees of TNM stage. Low expression of lncRNA PWRN1 and its potential regulating genes DMRTB1, PIRT, APOBEC1, and ZPBP2 were associated with better OS. Combining PWRN1 and four regulating genes as a signature, patients with higher-level expression of the signature had shorter survival time in not only the TCGA but also in the GEO dataset. Conclusions It was found that Tfh cells presented higher infiltration in LUSC current reformed smokers for ≤15 years and current smokers, while resting memory CD4 T cells had lower infiltration. The signature consisting of PWRN1 as well as its predicted targeted mRNAs was dysregulated in different levels of Tfh cell infiltration and might indicate patients’ OS.

Lung cancer is a highly prevalent type of cancer with a poor 5-year survival rate of about 4–17%. Eighty percent lung cancer belongs to non-small-cell lung cancer (NSCLC). For a long time, the treatment of NSCLC has been mostly guided by tumor stage, and there has been no significant difference between the therapy strategy of lung adenocarcinoma (LUAD) and squamous cell lung carcinoma (SCLC), the two major subtypes of NSCLC. In recent years, important molecular differences between LUAD and SCLC are increasingly identified, indicating that targeted therapy will be more and more histologically specific in the future. To investigate the LUAD and SCLC difference on multi-omics scale, we analyzed the methylation and gene expression data together. With the Boruta method to remove irrelevant features and the MCFS (Monte Carlo Feature Selection) method to identify the significantly important features, we identified 113 key methylation features and 23 key gene expression features. HNF1B and TP63 were found to be dysfunctional on both methylation and gene expression levels. The experimentally determined interaction network suggested that TP63 may play an important role in connecting methylation genes and expression genes. Many of the discovered signature genes have been supported by literature. Our results may provide directions of precision diagnosis and therapy of LUAD and SCLC.

Abstract Background Esophageal respiratory fistulae are abnormal communications between the esophagus and the respiratory system. They are either congenital or acquired. Most acquired esophageal respiratory fistulae are of the esophageal tracheal and esophageal bronchial type and are caused by infections or malignant neoplasms, whereas esophageal pulmonary fistulae are rare. Case presentation We report a case of a 72-year-old Caucasian man with squamous cell carcinoma of the lung presenting with abrupt-onset dyspnea during localized mediastinal radiotherapy. His laboratory test results suggested major respiratory infection. A chest x-ray revealed left apical lung radiopacity along with excavated lesions, consistent with secondary tumor infection. No clinical improvement was observed despite antibiotic treatment. A contrast-enhanced computed tomographic scan of the chest confirmed persistent lung infection with unfavorable progression and air in the mediastinum; the latter suggested a fistula from the upper third of the esophagus to the upper left pulmonary lobe. Videofluoroscopy confirmed the diagnosis of an acquired esophageal pulmonary fistula. The patient underwent endoscopy, and an esophageal self-expandable metallic stent was deployed. Conclusions Esophageal pulmonary fistulae must be suspected whenever patients undergoing local mediastinal radiotherapy present with acute pulmonary complications, particularly pneumonia resistant to antibiotic treatment. Esophageal pulmonary fistulae are diagnosed by means of radiological imaging. Because esophageal respiratory fistulae are acute life-threatening conditions, prompt treatment with an endoscopically placed covered stent proves vital.

Personalised cancer treatment depends on identification of therapeutically relevant biological subgroups of patients for assessing effect of treatment and to discover new therapeutic options. By analyses in heterogeneous patient populations, the effects may be lost in noise. Squamous cell carcinoma of the lung is a major killer worldwide. Despite recent advances, mortality is high and response to therapies varies greatly from patient to patient. Target search in biologically relevant subgroups may identify treatment options not so far discovered. A total of 198 patients undergoing surgery for squamous cell carcinomas of the lung were included in the study. The tumours were analysed for copy number alterations (n = 152) and gene expression from tumour (n = 188) and normal lung (n = 21), with both data levels present in 140 patients. We studied alterations in tumours harbouring mutations in TP53 and in previously published gene expression subtypes. Genes with consistent alterations in both genomic levels were identified as putative biomarkers. Results were validated in TCGA. The most convincing biomarker in TP53 mutated squamous cell carcinomas of the lung was BIRC5 with amplification in 36% of mutated samples, 5% in wild‐type samples and a 17%‐fold change of expression between TP53 mutated tumours and normal lung tissue. BIRC5 was significantly altered in the classical and primitive subtypes. We suggest BIRC5 as a putative predictive biomarker and putative druggable target in squamous cell lung carcinomas harbouring TP53 mutation or classified as classical and primitive subtypes. What's new? This study presents a target gene search combining copy number alteration and gene expression to identify putative genes for therapeutic and predictive approaches in TP53 mutated lung squamous cell carcinoma (SCC) and published gene expression subtypes with high percentages of TP53 mutations. Several potential biomarkers and therapeutic targets emerged from these pre‐defined biological subgroups. The results suggest that BIRC5 is one of the most appealing targets in TP53 mutated cancers and in the classical and primitive subtypes and should be tested clinically in these subgroups. Testing in biologically defined subgroups may increase likelihood of discovering clinically relevant treatment effects. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) and squamous cell lung carcinoma (SCC) are smoking-related diseases. However, the connection between the two is poorly understood. Microarray gene expression profiles in bronchial epithelium from patients with SCC with or without COPD were downloaded from the Gene Expression Omnibus repository. Differentially expressed genes associated with COPD and SCC were identified and visualized using the Advanced Network Merger module in Cytoscape. COPD-associated genes in SCC progression were further identified using the BisoGenet plug-in in Cytoscape. The genetic interaction network was predicted using the Network Analysis function. Heat shock protein 90 α family class A member 1 (HSP90AA1), adrenoceptor β2 (ADRB2), transducin β like 1 X-linked receptor 1 (TBL1XR1) and heat shock protein family B (small) member 1 (HSPB1) were identified to be differentially expressed in SCC and COPD cases. The overall survival rate associated with the gene signatures was investigated using clinical samples from patients with SCC and COPD from the PROGgene database. The results suggest that the pathogenesis of SCC caused by COPD is regulated by HSP90AA1, ADRB2, TBL1XR1 and HSPB1. These genes may serve as potential therapeutic targets for the treatment of patients with COPD-related SCC. [ABSTRACT FROM AUTHOR]

This is a case report of a 60-year-old diabetic, hypertensive male with a good performance status and a history of bilateral interstitial lung disease with a left upper lobe lung mass diagnosed to be a Stage IIB mixed small-cell/squamous cell carcinoma which was refractory to carboplatin- and etoposide-based chemotherapy. The patient was then taken up for adaptive intensity-modulated radiotherapy with tighter margin under image guidance with a mid-treatment replanning done at 25#. Acute toxicities were assessed weekly and showed no Grade 3 or more reactions. Pulmonary function test showed no detrimental changes during or after radiation. Response assessment at 12 and 20 weeks showed a partial response with decrease in metabolic activity on serial scans.

Tiziana Vavalà ASL CN1, SC Oncologia, Ospedale Civile di Saluzzo, Saluzzo, Cuneo, Italy Abstract: Lung cancer treatment has considerably changed over the last few years: the identification of druggable oncogenic alterations and innovative immunotherapic approaches granted lung cancer patients the possibility of more efficient and less toxic therapeutic options than chemotherapy. Nowadays, lung squamous cell carcinomas (SqCCs) patients have the chance to benefit from novel treatment alternatives, including immune checkpoint blockade and antiangiogenic agents and, given positive trial results, from afatinib, a second generation tyrosine kinase inhibitor (TKI) that irreversibly antagonizes ErbB family tyrosine kinase receptors. Considering the role of the ErbB-signaling cascade in lung SqCC, it is relevant to note that ErbB1 (epidermal growth factor receptor [EGFR]) is overexpressed in 85% of non-small-cell lung carcinomas (NSCLCs), particularly in patients with squamous histology, and is associated with poor prognosis. For this reason, EGFR activity has been investigated as a therapeutic strategy in lung SqCC. Even taking into account statistically positive trial results, anti-EGFR approach still remains controversial in unselected/wild-type EGFR lung SqCC patients, as well as the optimal timing and sequencing of all available targeted therapies considering the approval of immunotherapeutic agents. This review analyzes current data about EGFR inhibition in lung SqCC with a specific focus on afatinib in order to elucidate available clinical evidence supporting EGFR targeting in this setting as well as a future management of advanced lung SqCCs in the context of new emerging immunotherapeutic drugs. Keywords: lung cancer, NSCLC, tyrosine kinase inhibitor, LUX-Lung, EGFR, TKI

Competing Interests: Dr Correa is a consultant for Accutec, a consultant and researcher for Novartis Pharmaceutical and a researcher for Pfizer. She also serves on the Advisory Board for the Jacinto Convit World Organization and the Dermatology Advisory for Melanoma Research Foundation. All other authors declare no conflicts of interest.

Metabolic alterations that are critical for cancer cell growth and metastasis are one of the key hallmarks of cancer. Here, we show that thymidine kinase 1 (TK1) is significantly overexpressed in tumor samples from lung adenocarcinoma (LUAD) patients relative to normal controls, and this TK1 overexpression is associated with significantly reduced overall survival and cancer recurrence. Genetic knockdown of TK1 with short hairpin RNAs (shRNAs) inhibits both the growth and metastatic attributes of LUAD cells in culture and in mice. We further show that transcriptional overexpression of TK1 in LUAD cells is driven, in part, by MAP kinase pathway in a transcription factor MAZ dependent manner. Using targeted and gene expression profiling-based approaches, we then show that loss of TK1 in LUAD cells results in reduced Rho GTPase activity and reduced expression of growth and differentiation factor 15 (GDF15). Furthermore, ectopic expression of GDF15 can partially rescue TK1 knockdown-induced LUAD growth and metastasis inhibition, confirming its important role as a downstream mediator of TK1 function in LUAD. Collectively, our findings demonstrate that TK1 facilitates LUAD tumor and metastatic growth and represents a target for LUAD therapy. [ABSTRACT FROM AUTHOR]

Objective: Little is known about prognostic factors for lung squamous cell carcinoma (SCC). We aimed to explore radiologic and clinical factors affecting prognosis and to compare the prognosis of both central and peripheral lung SCCs. Materials and methods: Radiologic, clinical, and pathologic profiles of surgically confirmed SCCs from 382 patients were retrospectively reviewed. Tumor location, enhancement, necrosis, the presence of obstructive pneumonitis/atelectasis and underlying lung disease were evaluated on chest CT examination. Age, pulmonary function, tumor marker, and cancer stage were also assessed. Univariate and multivariate Cox regression analyses were performed to identify any correlation to overall survival (OS) and disease-free survival (DFS). Hazard rate estimation and competing risk analysis were done to evaluate recurrence pattern. Results: The median follow-up period was 56.2 months. Tumors were located centrally in 230 patients (60.2%) and peripherally in 152 patients (39.8%). Age (p = 0.002, hazard ratio [HR] 1.03, 95% confidence interval [CI] = [1.01, 1.06]) and interstitial lung abnormalities (ILAs) (p<0.001, HR 5.41, 95% CI = [3.08, 9.52]) were associated with poor OS on multivariate analysis. ILAs also had a strong association to DFS (p<0.001, HR 4.25, 95% CI = [3.08, 9.52]). Central cancers had two peaks of local recurrence development at 15 and 60 months after surgery, and peripheral tumors showed rising curves for metastasis development at 60 months. Conclusions: CT-determined ILAs are a strong biomarker predicting poor outcome. Prognosis may not vary according to tumor location, but the two groups exhibited different recurrence patterns. [ABSTRACT FROM AUTHOR]

Squamous cell lung carcinoma, epidermal growth factor receptor mutation, clinicopathologic features, tyrosine kinase inhibitors. [Extracted from the article]

• Bronchial premalignant lesions may progress to cancer or regress to normal mucosa. • The progression of bronchial lesions is governed by exo- and endogenous factors. • Tools should be developed to predict the progression of bronchial lesions to cancer. • Therapy should be considered for patients at high risk of developing lung cancer. Squamous cell carcinoma (SCC), one of the most common forms of lung cancer, shows accelerated progression and aggressive growth and usually is observed at advanced stages. SCC originates from morphological changes in the bronchial epithelium that occur during chronic inflammation: basal cell hyperplasia, squamous metaplasia, and dysplasia I-III. However, the process is not inevitable; it can be stopped at any stage, remain in the stable state indefinitely and either progress or regress. The reasons and mechanisms of different scenarios of the evolution of premalignant lesions in the respiratory epithelium are not fully understood. In this review, we summarized the literature data (including our own data) regarding genetic, epigenetic, transcriptomic and proteomic profiles of the premalignant lesions and highlighted factors (environmental causes, inflammation, and gene polymorphism) that may govern their progression or regression. In conclusion, we reviewed strategies for lung cancer prevention and proposed new models and research directions for studying premalignant lesions and developing new tools to predict the risk of their malignant transformation. [ABSTRACT FROM AUTHOR]

Alternative transcript isoforms are common in tumors and act as potential drivers of cancer. Mechanisms determining altered isoform expression include somatic mutations in splice regulatory sites or altered splicing factors. However, since DNA methylation is known to regulate transcriptional isoform activity in normal cells, we predicted the highly dysregulated patterns of DNA methylation present in cancer also affect isoform activity. We analyzed DNA methylation and RNA-seq isoform data from 18 human cancer types and found frequent correlations specifically within 11 cancer types. Examining the top 25% of variable methylation sites revealed that the location of the methylated CpG site in a gene determined which isoform was used. In addition, the correlated methylation-isoform patterns classified tumors into known subtypes and predicted distinct protein functions between tumor subtypes. Finally, methylation-correlated isoforms were enriched for oncogenes, tumor suppressors, and cancer-related pathways. These findings provide new insights into the functional impact of dysregulated DNA methylation in cancer and highlight the relationship between the epigenome and transcriptome. [ABSTRACT FROM AUTHOR]

Background: Multigene-based PCR tests are time-consuming and limiting aspects of the protocol include increased risk of operator-based variation. In addition, such protocols are complex to transfer and reproduce between laboratories. Aims: Evaluate the clinical utility of a pre-spotted PCR plate (PSP) for a novel multigene (n = 51) blood-based gene expression diagnostic assay for neuroendocrine tumors (NETs). Methods: A pilot study (n = 44; 8 controls and 36 NETs) was undertaken to compare CQ, normalized gene expression and algorithm-based output (NETest score). Gene expression was then evaluated between matched blood:tumor tissue samples (n = 7). Thereafter, two prospective sets (diagnostic: n = 167; clinical validation: n = 48, respectively) were evaluated for diagnostic and clinical utility value. Two independent molecular diagnostics facilities were used to assess assay reproducibility and inter-laboratory metrics. Samples were collected (per CLIA protocol) processed to mRNA and cDNA and then either run per standard assay (liquid primers) or on PSPs. Separately, matching plasma samples were analyzed for chromogranin A (CgA). Statistics included non-parametric testing, Pearson-concordance, Predictive Modeling and AUROC analyses. Results: In the pilot study (n = 44), CQ values were highly concordant (r: 0.82, p<0.0001) and normalized gene expression data significantly related (p<0.0001) (Pearson-pairwise correlation). NETest values were not different (49.7±33 standard vs. 48.5±31.5 PSP) and the overall concordance in output 96%. Predictive modelling confirmed this concordance (F1 score = 0.95). Gene expression levels were highly correlated between blood and tumor tissue (R: 0.71–0.83). In the diagnostic cohort (n = 30 controls, n = 87 non-NET controls, n = 50 NET), NETest was significantly lower (p<0.0001) in controls (11±6.5) and non-NET controls (13±18) than NETs (61±31). The AUROCs were 0.93–0.97 and the diagnostic accuracy was 90–97.5%. As a diagnostic, the PSP-NETest was significantly better than CgA (accuracy: 56%, p<0.0001). For clinical samples, the PSP generated robust and accurate (>96%) scores and was significantly better (p<0.0001) than CgA. The assay protocol was consistent (r: 0.97) and reproducible (co-efficient of variation: 1.3–4.2%) across the two facilities. Conclusion: The PSP protocol for the NETest has been established and prospectively tested in clinical samples. It is highly reproducible, has similar metrics (CV, categorization by control or NET) to the standard PCR assay and generates clinically concordant (>96%) NETest results. Moreover, it functions significantly more accurately than CgA. [ABSTRACT FROM AUTHOR]

Aim: To in detail delineate sex differences in non-small cell lung cancer outcome and investigate possible underlying drivers. Methods: We performed a nationwide, population-based cohort study using data on all incident cases of lung squamous cell carcinoma (n = 10,325) and adenocarcinoma (n = 23,465) recorded in the Swedish Lung Cancer Register in 2002–2016. Flexible parametric models were applied to compute adjusted female-to-male hazard ratios (aHRs) and standardized survival proportions over follow-up including age, calendar year, education, marital status, birth country, health care region, performance status, smoking history, comorbidities, and tumor location in the final model. Results: Women presented with better performance status, were younger, and more often never-smokers. Women with adenocarcinoma also had lower comorbidity burden, less advanced stage, and were more often EGFR positive. Men with adenocarcinoma had a consistently poorer lung cancer-specific survival across stage; HR 0.69; 95% CI 0.63–0.76 (stage IA-IIB) to 0.94; 95% CI 0.88–0.99 (stage IIIB-IV), remaining largely unchanged after adjustments; aHR 0.74; 95% CI 0.66–0.82 to 0.84; 95% CI 0.81–0.87. The same pattern was observed in squamous cell carcinoma, except in stage IIIA disease, where we found no sex differences in survival. Conclusions: Men with non-small cell lung cancer have a consistently poorer prognosis, even after careful adjustments for a wide range of prognostic factors. While the pattern was similar in both squamous cell and adenocarcinoma, it was larger and more consistent in the latter. [ABSTRACT FROM AUTHOR]

Background: Neuroendocrine neoplasms (NENs) can arise in most of the epithelial organs of the body and are not a rare condition in the gastrointestinal tract (GIT). The presence of NENs in GIT associated with other secondary primary malignancies (SPM) has been considered an exotic event. This study aims to describe the case reports of NENs accompanied by synchronous primary tumors. Methods and findings: We performed a systematic literature search of the databases Scopus, PubMed, Scielo and LILACS to identify case reports that described the presence of NENs in GIT with SPM. 78 case reports were included. The mean of age of the cases was 60.2 years. 60% were male. 95.4% were NENs G1. 17 cases of NENs had metastasis. 80% of SPM were recognized in the GIT (36% in stomach, 27% in large intestine, 11.2% in small intestine, and 5.6% in esophagus). The most common type of SPM was adenocarcinoma (49.4%), followed by GIST (13.5%), other NENs in different GIT segment (7.9%), lymphoma (6.8%), and squamous cell carcinoma (4.5%). The most common tumor in GIT was adenocarcinoma (97.6%) and the presence of adenocarcinoma in the same segment of GIT was found in 68.4% of the cases. Association between adenocarcinomas and NENs in GIT (p:<0.0001) and adenocarcinoma and tumor in the same segment of GIT location were observed (p<0.001). Conclusion: These results demonstrate that NENs with SPM are not a rare condition. Several theories have been proposed to explain this association; one of these is the ability of NENs to generate synchronous tumors by autocrine and paracrine effect. We observed an association between adenocarcinomas and NENs in the same segment of GIT. [ABSTRACT FROM AUTHOR]

Introduction: Aberrant expression of RNA-binding motif protein 3 (RBM3) has been suggested as a prognostic biomarker in several malignancies. Materials and methods: This study was performed to analyse the prevalence and clinical significance of RBM3 immunostaining in non-small cell lung cancers (NSCLCs). Therefore, we took advantage of our tissue microarray (TMA) containing more than 600 NSCLC specimens. Results: While nuclear RBM3 staining was always high in normal lung tissue, high RBM3 staining was only seen in 77.1% of 467 interpretable non-metastatic NSCLCs. Reduced RBM3 staining was significantly associated with advanced pathological tumor stage (pT) in NSCLCs (p = 0.0031). Subset analysis revealed that the association between reduced RBM3 staining and advanced pT stage was largely driven by the histological subgroup of lung adenocarcinoma (LUACs) (p = 0.0036). In addition, reduced RBM3 expression predicted shortened survival in LUAC patients (p = 0.0225). Conclusions: In summary, our study shows that loss of RBM3 expression predicts worse clinical outcome in LUAC patients. [ABSTRACT FROM AUTHOR]

Centrosome amplification (CA) is a common feature of human tumours and a promising target for cancer therapy. However, CA’s pan-cancer prevalence, molecular role in tumourigenesis and therapeutic value in the clinical setting are still largely unexplored. Here, we used a transcriptomic signature (CA20) to characterise the landscape of CA-associated gene expression in 9,721 tumours from The Cancer Genome Atlas (TCGA). CA20 is upregulated in cancer and associated with distinct clinical and molecular features of breast cancer, consistently with our experimental CA quantification in patient samples. Moreover, we show that CA20 upregulation is positively associated with genomic instability, alteration of specific chromosomal arms and C>T mutations, and we propose novel molecular players associated with CA in cancer. Finally, high CA20 is associated with poor prognosis and, by integrating drug sensitivity with drug perturbation profiles in cell lines, we identify candidate compounds for selectively targeting cancer cells exhibiting transcriptomic evidence for CA. [ABSTRACT FROM AUTHOR]

Triple negative breast cancer (TNBC) is an aggressive tumor with propensity to metastasize and poor treatment options. Improving treatment options would be impactful; thus, finding a tumor-specific cell surface protein with metastasis promoting functions that could be knocked out was the goal of this study. The Otoconin 90 gene (OC90), frequently amplified in tumors on chromosome 8q24.22, was identified as a potential therapeutic candidate. Normally OC90 is expressed in the cochlea with no known function in other normal tissues. In silico analysis of The Cancer Genome Atlas (TCGA) multi-tumor RNAseq cohorts revealed that OC90 is expressed in many tumor types at high prevalence and genomic amplification is associated with the elevated mRNA expression. In vitro assays in TNBC cell lines revealed OC90 expression with control over cell viability, apoptosis and invasion. RNA-seq analysis of OC90-siRNA knockdown and OC90-overexpression in BT20, BT549, HCC38 cell lines identified co-expressed transcripts, HMGA2, POLE2 and TRIB3. Altered expression of HMGA2, POLE2 and TRIB3 was predictive of survival among members of the Metabric breast cancer cohort. Thus, OC90 represents a potential therapeutic target whose knockdown could improve the treatment of TNBC. [ABSTRACT FROM AUTHOR]

Patients with stage IIIA/IIIB squamous non-small cell lung cancer (SqCLC) are particularly challenging to treat with a poor 5-year survival rate and new treatment strategies are needed. In the present study, a retrospective, single-center study was conducted to explore the efficacy and safety of Endostar combined with chemotherapy as the neoadjuvant treatment in patients with stage IIIA/IIIB SqCLC. A total of 27 patients with locally advanced SqCLC treated with Endostar combined with chemotherapy as neoadjuvant therapy from January 1, 2017 to December 31, 2019 at the Zhejiang Cancer Hospital (Hangzhou, China) were included. Short-term efficacy, rate of surgical resection, long-term outcome and adverse events were analyzed. After treatment with Endostar combined with chemotherapy, 37% of the patients underwent surgery and the radical resection rate was 90%. The objective response rate was 63% for the total population and 80% for patients who received surgery. Of note, 100% of the patients achieved disease control after treatment with Endostar combined with chemotherapy. In patients who underwent surgical resection, postoperative pathology showed that 100% of the patients achieved pathological downstaging. Furthermore, 1 (10%) patient showed a pathological complete response after surgery. The median progression-free survival was 13.5 months and overall survival was 27.9 months for the total cohort. The most common adverse events (AEs) were anemia (69.4% of patients), followed by hypertension (29.6% of patients). Most of the AEs were grade 1–2 and only 4 patients (14.8%) developed grade 3–4 AEs. Endostar combined with chemotherapy was well-tolerated and showed promising efficacy in patients with stage IIIA/IIIB SqCLC. Further prospective studies are warranted to explore its value as a neoadjuvant therapy. [ABSTRACT FROM AUTHOR]

Non-small cell lung carcinoma (NSCLC) includes squamous cell carcinoma, adenocarcinoma and large cell carcinoma. Subtyping of NSCLC is essential for therapy. Classification of NSCLC into more specific histological subtypes is carried out by morphologic examination or immunohistochemistry. The aim of this study was immunohistochemical analysis of NSCLC (squamous cell carcinoma and adenocarcinoma) in bronchoscopic biopsies. Formalin-fixed, paraffin-embedded bronchoscopic mucosal samples from 40 patients with NSCLC (20 patients with squamous cell carcinoma and 20 patients with adenocarcinoma) were retrieved from pulmonary pathology archives at Center for Pathology and Pathological Anatomy, Clinical Center Niš. Serial histological sections of 4 µm thickness were stained with hematoxylin and eosin, and immunohistochemical method DAKO LSAB for TTF-1, p63, and CK5/6 antibodies. Positive immunoreactivity for p63 was found in 95% of squamous cell carcinomas (19/20), while for CK5/6 in 90% of squamous cell carcinomas (18/20), and in 5% of adenocarcinomas (1/20). In 80% of adenocarcinomas (16/20), a positive TTF-1 immunophenotype was found, while all squamous cell carcinomas were negative for this marker (0/20). Immunohistochemical analysis (panel p63, CK5/6 and TTF-1) is a useful ancillary tool for distinguishing squamous cell lung carcinoma from adenocarcinoma in bronchoscopic biopsy specimens.

Purpose: to study argyrophilic proteins associated with nucleolar organizer regions (Ag-NOR proteins) in proliferating cells in relationship between the clinical and morphological parameters and survival in squamous cell lung carcinoma. Materials and methods: One hundred and thirteen surgical specimens of squamous cell lung cancer were studied using double staining for Ki-67 antigen (MIB-1 clone, DAKO) by immunohistochemistry and for Ag-ЯОР-proteins with silver nitrate. results: In squamous cell carcinoma, the Ag-NOR area in Ki-67 positive cells correlated with the clinical and morphological parameters: parameter T, the greatest tumor size, parameter N, stage of the disease and tumor differentiation. When the area of Ag-ЯОР-proteins in Ki-67 positive cells was small, the long-term survival rates were higher. The Ag-ЯОР area in Ki-67 positive cells is an independent prognostic factor in squamous cell lung cancer.

Background: HER2 mutations are identified in approximately 2% of non-small-cell lung cancer (NSCLC) cases and are predominantly observed in non-smokers, females, and adenocarcinoma patients. Although afatinib is recommended for treating NSCLC patients with HER2 mutation, the therapy is most efficacious in patients harboring HER2 exon 20 insertions, especially the in-frame insertion YVMA. Research on the treatment of the extracellular domain mutation is relatively rare. Case presentation: We discuss a 76-year-old Chinese man with a heavy-smoking history who was diagnosed with stage IV squamous cell lung carcinoma. First-line treatment with the angiogenesis inhibitor endostar and systemic chemotherapy with docetaxel plus cisplatin were administered, but the patient ceased treatment because of chemotherapy-induced adverse events. Based on the test result from an amplification refractory mutation system PCR, EGFR-inhibitor icotinib was prescribed, but there was still no evidence of a response. Then, next-generation sequencing identified an HER2 S310Y mutation, and afatinib therapy resulted in a gradual, but substantial reduction in tumor size. Conclusion: This is the first published case report of the successful management of HER2 S310Y mutation squamous cell lung carcinoma with afatinib. Considering the fact that this rare HER2 mutation clinically benefited from afatinib treatment, attention should be paid to the incidence of HER2 in NSCLC patients with inconsistent histological characteristics compared with those previous published. With the guidance of a precise diagnosis, we should realize the significance of other HER2 gene mutations and next-generation sequencing as a diagnostic method. [ABSTRACT FROM AUTHOR]

Prediction of lung cancer metastasis relies on post-resection assessment of tumor histology, which is a severe limitation since only a minority of lung cancer patients are diagnosed with resectable disease. Therefore, characterization of metastasis-predicting biomarkers in pre-resection small biopsy specimens is urgently needed. Here we report a biomarker consisting of the phosphorylation of the retinoblastoma protein (Rb) on serine 249 combined with elevated p39 expression. This biomarker correlates with epithelial-to-mesenchymal transition traits in non-small cell lung carcinoma (NSCLC) cells. Immunohistochemistry staining of NSCLC tumor microarrays showed that strong phospho-Rb S249 staining positively correlated with tumor grade specifically in the squamous cell carcinoma (SCC) subtype. Strong immunoreactivity for p39 positively correlated with tumor stage, lymph node invasion, and distant metastases, also in SCC. Linear regression analyses showed that the combined scoring for phospho-Rb S249, p39 and E-cadherin in SCC is even more accurate at predicting tumor staging, relative to each score individually. We propose that combined immunohistochemistry staining of NSCLC samples for Rb phosphorylation on S249, p39, and E-cadherin protein expression could aid in the assessment of tumor staging and metastatic potential when tested in small primary tumor biopsies. The intense staining for phospho-Rb S249 that we observed in high grade SCC could also aid in the precise sub-classification of poorly differentiated SCCs. [ABSTRACT FROM AUTHOR]