Primary Lung Tumors Research Articles

CyberKnife® stereotactic radiation therapy for stage I lung cancer and pulmonary oligometastases: is fiducial implantation still relevant?-a cohort study.

Few studies have investigated whether there is a difference in local control or overall survival rates following treatment with robotic stereotactic body radiation therapy (SBRT) with or without prior fiducial marker implantation. Our study aimed to investigate this in patients with primary or secondary lung tumors. A retrospective study was conducted at the Institut de Cancérologie de Lorraine of patients treated for primary lung cancer or pulmonary oligometastases with SBRT from January 2013 to July 2016. We included patients at least 18 years old who had stage I non-small cell lung cancer (NSCLC) or lung metastases and a follow-up of at least 1 month. A total of 294 patients were included. Tumors included 122 lung metastases, 89 stage I NSCLC, and 83 non-histologically confirmed lung lesions. The tracking methods were Synchrony® in 191 cases (119 gold seeds and 72 coils) and Xsight® Spine with 4D computed tomography in 103 cases. Median follow-up was 31.6 months [interquartile range (IQR), 18.1-50.2 months]. The two- and five-year probability of local control were respectively 92.22% [95% confidence interval (CI): 0.89-0.95] and 85.35% (95% CI: 0.79-0.99). The two- and five-year probability of overall survival were respectively 87.46% and 72.77% (P=0.586). Local control rates did not significantly differ between techniques at 2 and 5 years (P=0.685) (gold seeds, coils or Xsight® Spine) within tumors grouped by location, gross tumor volume (GTV) (respectively P=0.9, P=0.7, and P=0.4), planning target volume (PTV) (respectively P=0.4, P=0.9, and P=0.7), or PTV/GTV ratio (respectively P=0.6, P=0.6, and P=0.5). Metastasis-free survival and Overall survival rates did not significantly differ between techniques at 2 and 5 years (P=0.664 and P=0.586, respectively). There were no grade 4 or 5 toxicities and only one grade 3 pneumonitis and one grade 3 pneumothorax. Fiducial-less SBRT using Xsight® Spine is a safe alternative to Synchrony® using gold seeds or coils, with comparable local control and overall survival rates and a similar toxicity profile.

427 Systemic Imaging for Early Laryngeal Cancer; a Single Centre Review of Guideline Application in Contemporary Clinical Practice

Abstract Aim Early-stage laryngeal cancer (T1 and T2) has low rate of locoregional and distant metastasis. Therefore, National Institute for Health and Care Excellence (NICE) guidelines were updated in 2016 and recommended to no longer offer systemic staging for early laryngeal cancer because systemic imaging was not deemed to be cost effective. Our study aims to evaluate (1) if NICE guidance on the role of systemic imaging in the assessment and management of early laryngeal cancer is being followed in our centre (2) assess the impact of this practice on our patients (3) perform a cost analysis relevant to our institution. Method We retrospectively reviewed all laryngeal cases at a major H&N cancer centre between 01/01/2020 and 01/01/2022. The following information was collected for all the patients: neck/systemic imaging modalities performed on patients, demographics, site of original laryngeal tumour and any metastatic disease detected by systemic imaging. Next, we performed a cost analysis based on the cost analysis method undertaken by NICE. Results Our results showed n = 83 patients had laryngeal cancer between 01/01/2020 and 01/01/2022. Of which n = 30 had T1N0 and T2N0 disease. Systemic imaging found no metastatic disease, however n = 2 primary lung tumours and n = 1 lung infection was detected. The total cost for systemic imaging was £4,207.12 and total cost for neck imaging investigations it was £12,335.07. Conclusions Our study concludes NICE guidance is not being followed at our centre. Systemic imaging provides little benefit to patients and is an expensive practice.

Assessing the role of positron emission tomography and bone scintigraphy in imaging of pleuropulmonary blastoma (PPB): A report from the International PPB/DICER1 Registry.

Pleuropulmonary blastoma (PPB) is the most common primary lung neoplasm of infancy and early childhood. Given the rarity of PPB, the role of positron emission tomography (PET) and bone scintigraphy (bone scans) in diagnostic evaluation and surveillance has not been documented to date. Available PET and bone scan data are presented in this study. Patients with PPB enrolled in the International PPB/DICER1 Registry and available PET imaging and/or bone scan reports were retrospectively abstracted. On retrospective analysis, 133 patients with type II and III (advanced) PPB were identified with available report(s) (PET scan only=34, bone scan only=83, and both bone scan and PET=16). All advanced primary PPB (n=11) and recurrent (n=8) tumors prior to treatment presented with 18 F-fluorodeoxyglucose (FDG)-avid lesions, with median maximum standardized uptake values of 7.4 and 6.7, respectively. False positive FDG uptake in the thorax was noted during surveillance (specificity: 59%). Bone metastases were FDG-avid prior to treatment. Central nervous system metastases were not discernable on PET imaging. Sensitivity and specificity of bone scans for metastatic bone disease were 89% and 92%, respectively. Bone scans had a negative predictive value of 99%, although positive predictive value was 53%. Four patients with distant bone metastases had concordant true positive bone scan and PET. Primary, recurrent, and/or extracranial metastatic PPB presents with an FDG-avid lesion on PET imaging. Additional prospective studies are needed to fully assess the utility of nuclear medicine imaging in surveillance for patients with advanced PPB.

A Machine Learning-Based Model to Predict In-Hospital Mortality of Lung Cancer Patients: A Population-Based Study of 523,959 Cases.

Background: Stratify new lung cancer patients based on the risk of in-hospital mortality rate after diagnosis. Methods: 522,941 lung cancer cases with available data on the Surveillance, Epidemiology, and End Results (SEER) were analyzed for the predicted probability based on six fundamental variables including age, gender, tumor size, T, N, and AJCC stages. The patients were randomly assigned to the training (n = 115,145) and validation datasets (n = 13,017). The remaining cohort with missing values (n = 394,779) was then combined with the primary lung tumour datasets (n = 1018) from The Cancer Genome Atlas, Lung Adenocarcinoma and Lung Squamous Cell Carcinoma projects (TCGA-LUAD & TCGA-LUSC) for external validation and sensitivity analysis. Results: Receiver Operating Characteristic (ROC) analyses showed high discriminatory power in the training and internal validation cohorts (Area under the curve [AUC] of 0.78 (95%CI = 0.78-0.79) and 0.78 (95%CI = 0.77-0.79), respectively), whereas that of the model on external validation data was 0.759 (95%CI = 0.757-0.761). We developed a static nomogram, a web app, and a risk table based on a logistic regression model using algorithm-selected variables. Conclusions: Our model can stratify lung cancer patients into high- and low-risk of in-hospital mortality to assist clinical further planning.

Ten years outcomes after SABR in central and ultracentral primary lung tumors

PurposeSABR performed for central and ultracentral lung tumors is associated with increased toxicity but limited data is available on late toxicities. We studied toxicity in patients followed-up ≥ 2 years post-SABR at a single-institution. MethodsAll patients were treated using VMAT for a primary or recurrent central lung cancer between 2008–2015. 60 Gy was delivered in 8 or 12 fractions. Grade ≥ 3 clinical and radiological bronchial toxicity was scored. Multivariable Cox regression models were used to estimate hazard ratios. ResultsOf 127 eligible patients, 63% were treated with 8 fractions. Median tumor diameter was 4.4 cm (range 1.3–12.0). Median overall survival was 25.0 months (95% CI 16.5–33.5); 4% developed isolated local recurrences. The actuarial 5-year rate for severe clinical toxicity was 34.1% (95% CI 21.2–44.9). Both clinical toxicity and fatal lung haemorrhage were most observed when tumors were located ≤ 1 cm from the trachea or main bronchi (46% of all cases). The 5-year actuarial rate of radiological bronchial toxicity was 37.5% (95% CI 21.5–50.2). Multivariable analysis revealed that a performance score of 2 or 3 (HR 3.6; 95% CI 1.7–7.8), and tumor location ≤ 1 cm from the trachea or main bronchi (HR 4.3; 95% CI 1.2–14.9) were significant predictors for severe clinical toxicity. ConclusionThe actuarial rates for both severe clinical and radiological bronchial toxicity after central SABR was approximately 35% in patients surviving 5 years. Patients with tumors located ≤ 1 cm from the trachea or main bronchus were at the highest risk for severe clinical toxicity.

Difficulties in diagnosing a myofibroblastic lung tumor in a child

Inflammatory myofibroblastic tumor (VMO) is a rare neoplasm, which is currently referred to as a mesenchymal neoplasm with intermediate biological potential. The tumor consists of differentiated myofibroblastic fusiform cells. The frequency of occurrence of VMO among primary lung neoplasms is up to 1%. This type of tumor is the most common type of primary lung tumors in children. VMO can occur both in childhood and in adulthood. VMO is found in the soft tissues of the abdominal cavity, in the pelvic organs, larynx, mammary gland, head and neck tissues. Extra-organ localization (retroperitoneal space, mediastinum) is also diagnosed. Lung VMO often has no clinical manifestations, and if present has nonspecific symptoms, such as cough, hemoptysis, shortness of breath, hyperthermia, chest pain. VMO was previously considered as a neoplasm with a benign course, but these tumors tend to local relapses and distant metastasis. The article presents data on the prevalence, clinical manifestations and treatment of VMO, as well as own clinical observation of the course of this disease in an 8-year-old child.

Role of cytoblock on pleural effusion for diagnosis of malignant disease.

Thoracocentesis of pleural effusion is a simple technique for pleural fluid examination through cytology. In addition to cytological examination to assess the nature of pleural fluid content, we can also perform more detailed examinations through cytoblocks of residual fluid. These paraffin-embedded cytoblock samples are important because we can perform examinations as in other bioptic samples. In these samples, immunohistochemical and molecular analyses can be performed. Two hundred fifty-five cytological samples from patients with pleural effusion were examined. In cases in which the presence of malignant cells was identified in the cytological examination, as well as cases that were suspicious but not definitive for the presence of a malignant effusion, a cytoblock was prepared. Histological examination and immunohistochemical analysis were performed. Among 255 cases with pleural effusion, 152 had the presence of malignant cells and 6 cases were suspicious, but uncertain for the presence of malignant cells, while 86 cases had inflammatory pleural effusion or other pathologies but were not malignant. After histological analysis of the cytoblock and immunohistochemical analysis, we identified 82 malignant tumors of the lung, 8 malignant tumors of the gastrointestinal tract, 15 malignant tumors of the breast, and 6 malignant tumors of the female genital tract, as well as 24 tumors of undetermined origin. Cytoblocks are important for the diagnosis of the primary nature of malignant pleural effusions. The highest importance is primary lung tumors, as well as those tumors in which the primary site of the tumor cannot be determined clinically.

BSBM-16 HLA CLASS-I ANTIGEN PRESENTATION MACHINERY AND IFN-γ PATHWAY ALTERATIONS IN LUNG CANCER BRAIN METASTASES

Abstract BACKGROUND Immune checkpoint inhibitors (ICI) can have activity in lung cancer brain metastases (LBM). However, the duration of responses is limited and most patients with LBM do not benefit from these therapies. Alterations in HLA class-I antigen presentation machinery via beta-2 microglobulin (B2M) downregulation and disruption of IFN-γ sensing were identified as mechanisms of immune evasion and ICI resistance in solid tumors. However, the expression and clinical significance of these pathways in LBM are poorly understood. METHODS Using multiplex quantitative immunofluorescence we measured the localized expression of B2M protein; and the IFN-γ pathway markers phospho-STAT1 (pSTAT1), and Interferon Regulatory Factor 1 (IRF-1) in 67 immunotherapy naïve LBM and 45 primary lung tumors (PLT), including 15 patients with paired samples represented in a tissue microarray. The markers were selectively measured in cytokeratin + tumor cells and in cytokeratin- stromal cells. Associations between the markers, PD-L1, TILs and clinicopathologic variables were compared between LBM and PLT. RESULTS LBM showed lower levels of B2M in both tumor and stroma compartments compared to PLT. In contrast, high tumor and stromal levels of pSTAT1 were observed in LBM and comparable levels of IRF-1 were found between both tumor sites. Consistently across LBM and PLT samples, pSTAT1 and IRF1 were strongly correlated, and a positive but weaker association was observed with B2M and TILs. Only in PLT high tumor-cell PD-L1 expression was associated with high levels of IRF-1. No statistically significant association was observed between the markers and clinicopathologic variables. Tumor B2M downregulation in PLT was associated with worse survival. CONCLUSION LBM show distinct immunomodulatory properties relative to PLT, characterized by reduced HLA class-I antigen presentation machinery, elevated IFN-γ signaling and reduced local adaptive immune responses. These results support differences in immune evasion mechanisms in LBM compared with the PLT, which may have biological and clinical implications.

BSBM-09 IN VIVO CRISPR ACTIVATION SCREEN IDENTIFIES ß-SITE AMYLOID PRECURSOR PROTEIN CLEAVING ENZYME 1 (BACE1) AS A DRIVER OF NON-SMALL CELL LUNG CANCER BRAIN METASTASIS

Abstract Brain metastasis occurs in up to 40% of patients with non-small cell lung cancer (NSCLC). Considerable genomic heterogeneity exists between the primary lung tumour and respective brain metastasis; however, the identity of the genes capable of driving brain metastasis is incompletely understood. Here, we carried out an in vivo genome wide CRISPR activation (CRISPRa) screen to identify molecular drivers of brain metastasis from a NSCLC patient-derived xenograft model. We identified activation of the Alzheimer’s disease associated ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) led to a significant increase in brain metastasis. BACE1 is highly expressed in NSCLC and patients with BACE1 expressed in their metastatic brain tumour survived for shorter periods. Genetic loss with CRISPR-Cas9 or pharmacological inhibition of BACE1 with MK-8931 decreased cell proliferation and sphere forming capacity in vitro. Furthermore, BACE1 knockout and MK-8931 treatment blocked brain metastasis in vivo. Mechanistically, we identified BACE1 activation lead to downstream signalling through MEK and ERK. Together our data highlights the power of in vivo CRISPR screening to identify novel molecular drivers and potential therapeutic targets of NSCLC brain metastasis.

BSBM-11 COMBINING IMMUNOTHERAPY AND WHOLE-BRAIN RADIATION THERAPY IN A NOVEL SYNGENEIC LUNG CANCER BRAIN METASTASIS PRECLINICAL MODEL: DOES TIMING OF ADMINISTRATION MATTER?

Abstract Approximately 50% of all brain metastasis cases originate from primary lung tumors. Whole-brain radiation therapy (WBRT) is a common treatment for patients with multiple brain metastases, but patients rarely survive longer than one year after diagnosis. Recent studies demonstrate improved outcomes with combinatorial radiotherapy and immunotherapy, but the optimal timing of immunotherapy administration is unclear. Eliciting a robust immune response post-immunotherapy is vital for therapeutic efficacy. Our work shows that the BBB is disrupted and proinflammatory cytokines are increased in the brain 12 hours post-WBRT in immunocompetent but not immunocompromised mice. Additionally, efflux transporter activity is decreased at this time point. This study utilizes a novel Lewis Lung Carcinoma cell line, LLC-Br, which was developed in our laboratory to preferentially metastasize to the brain. Mice were treated with immune checkpoint inhibitors (ICIs) before or after WBRT then we evaluated tumor progression, survival, and blood-tumor barrier (BTB) permeability. We hypothesized administration of ICI following WBRT would increase survival, decrease tumor burden, and increase BTB permeability in our preclinical syngeneic lung cancer brain metastasis model.

BSBM-10 CHARACTERIZATION OF A RADIATION-RESISTANT MODEL OF LUNG CANCER BRAIN METASTASIS

Abstract Lung cancer is the most common cancer to metastasize to the brain, with 50% of all brain metastases originating from lung primary tumors. Traditional therapy for lung cancer brain metastases includes surgical resection, radiation, and chemotherapy. Due to the presence of the blood-tumor barrier, penetration of therapeutics is significantly hindered. Even when used in combination, tumor recurrence and regrowth after initial chemoradiotherapy remain a significant issue. To recapitulate recurrent disease, we aim to characterize a radio-resistant preclinical model of brain metastasis to investigate its effect on growth, chemosensitivity, and drug permeation across the blood-tumor barrier. Herein, we have generated a human NSCLC cell line bearing EGFR exon 19 deletion (PC9) that has been serial passaged in mice to colonize brain (PC9-Br). PC9-Br cells were serially irradiated and allowed to proliferate for 10-14 days prior to re-irradiation. The total dose administered to PC9-Br cells was 60 Gy to generate a radioresistant population (PC9-Br-RR). Clonogenic, MTT, and SRB analysis indicates a significant increase in survival percentage of PC9-Br-RR compared to PC9-Br irradiation at 2, 4, 6, and 8 Gy. While PC9-Br-RR cells are more resistant to cisplatin than PC9-Br (IC50: 2.5 µM and 1.5 µM, respectively at 72 h), they are more sensitive to osimertinib in vitro (IC50: 6.9 nM and 33 nM, respectively at 72 h). In vivo, PC9-Br-RR tumors developed more rapidly in mice than PC9-Br and brain-to-body tumor burden analysis showed PC9-Br-RR cells have increased brain tropism. Collectively, this data supports the characterization of a radio-resistant brain metastasis model to investigate the role of acquired radio-resistance at the blood-tumor barrier.

Long-term survival outcome of radiation therapy for unresectable, locally advanced non-small cell lung cancer: Single center experience at Hospital 175.

142 Background: Lung cancer represents a significant global health burden, with non-small cell lung cancer (NSCLC) being the most prevalent form of this disease. While surgery remains the cornerstone of treatment for early-stage NSCLC, patients with locally advanced or inoperable NSCLC require alternative therapeutic strategies. Purpose: to assess the long-term survival data and determine the associated factors impacting survival outcomes for patients with locally advanced unresectable non-small cell lung cancer (NSCLC) treated with radiotherapy. Methods: We retrospectively analyzed patients diagnosed with inoperable stage III of NSCLC who received radiation therapy at Hospital 175 from January 2019 to June 2022. The patients had a performance status score (PS) of 0-2 and only one primary lung tumor. We collected patients' background information, including age, gender, pathology, TNM, combination chemotherapy, PET/CT characteristics, and radiotherapy plan parameters. All patients received radiotherapy, at a dose equivalent to 60Gy or more. During radiation therapy, patients were monitored for radiation toxicity. We used the Kaplan-Meier method to estimate overall survival (OS) rate and the Cox regression model to identify the risk factors affecting the treatment outcomes. Results: A total of 240 cases, male: 75%, PS 0, 1, 2 respectively: 24%, 72%, 4%. Histopathological types: squamous cell (9%), glandular cell (83.5%), others (7.5%). Which, subgroups of stages IIIA, IIIB, and IIIC: are 32%, 48%, and 20%. The rate of patients having chemotherapy before radiation was 80.3%, and having PET/CT scans was 43.5%. Patients with radiation alone: 73.4% and concurrent chemoradiotherapy: 26.6%. Median follow-up time: 16.3 months, median OS: 19.5 months. OS rates after 1, 2, and 3 years are 76.2%, 38.8%, and 27.4%, respectively. The most common toxicity was grade 2 esophagitis. Patients who received concurrent chemoradiotherapy had a better prognosis than those who received radiation therapy alone. Regimen of radiation therapy, age, histopathological type, and lymph node metastasis were significant factors affecting overall survival outcomes. Conclusions: Radiotherapy is an essential part of treatment for inoperable NSCLC. The best survival benefit is achieved with concurrent chemoradiotherapy. Besides, age, lymph node metastasis, and histopathological type are also potential factors that can influence patient outcomes.

Circulating hsa_circ_0072309, acting via the miR-100/ACKR3 pathway, maybe a potential biomarker for the diagnosis, prognosis, and treatment of brain metastasis from non-small-cell lung cancer.

One of the main causes of lung cancer-related death is brain metastasis (BM). Finding early indicators of BM derived from lung cancer is crucial. Therefore, this study was designed to determine if serum hsa_circ_0072309 may be employed as a potential biomarker for BM induced by non-small-cell lung cancer (NSCLC) and to understand its possible underlying mechanism. Primary lung cancer and healthy neighboring tissues were obtained from all patients, while BM tissues were taken from BM+ patients. Serum specimens were collected from all patients and healthy volunteers. Hsa_circ_001653, miR-100, and ACKR3 RNA expressions were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and atypical chemokine receptor 3 (ACKR3) protein expression by western blotting (WB), immunohistochemistry (IHC), and enzyme-linked immunosorbent assay (ELISA). In order to examine the effect of serum hsa_circ_0072309 and its relevant mechanism on BM development, an NSCLC-associated BM model in mice was established. According to the results, miR-100 expression was down-regulated in primary lung cancer tissues compared to healthy lung tissues in all NSCLC patients, and circ_0072309 and ACKR3 expression were up-regulated. In BM tissues compared with primary lung tumors of BM+ patients, in serum samples from all patients compared to healthy volunteers, and in lung tumors of BM+ patients compared to those from BM- patients. Patients' serum exhibits the same level of hsa_circ_0072309/miR-100/ACKR3 expression as in BM samples. Advanced tumor-node-metastasis (TNM) stage, higher BM, shorter post-operative overall survival (OS), and progression-free survival (PFS) are all substantially associated with increased serum circ_0072309 levels in BM+ patients. In animal models, serum owning hsa_circ_0072309 from BM+ patients facilitates BM formation by regulating the miR-100/ACKR3 pathway. The current preliminary research reveals serum hsa_circ_0072309 as a possible biomarker and target for early diagnosis, prognosis, and therapy of NSCLC-derived BM and suggests a substantial role for the hsa_circ_0072309/miR-100/ACKR3 axis in the formation of BM from NSCLC.

Incidental Metaplastic Primary Pulmonary Meningioma.

Primary pulmonary meningioma is a rare benign tumor usually presenting as a solitary pulmonary nodule or mass. It can be easily misinterpreted as a primary lung tumor or metastases on imaging studies. We present a 54-year-old woman with an incidentally discovered solitary lung nodule, which was diagnosed as metaplastic primary pulmonary meningioma following resection. Metaplastic meningioma is a rare WHO grade 1 meningioma subtype with focal or global mesenchymal differentiation. To the authors' knowledge, primary pulmonary meningioma with mesenchymal differentiation has not been described previously in the English literature.

Investigations of the distant metastatic non-small cell lung cancer without local lymph node involvement: Real world data from a large database.

This study aimed to investigate the presentations and survival outcomes of the distant metastatic non-small cell lung cancer (NSCLC) without lymph node involvement to obtain a clearer picture of this special subgroup of metastatic NSCLC. A least absolute shrinkage and selection operator (LASSO) penalized Cox regression analysis was used to select the prognostic variables. A nomogram and corresponding risk-classifying systems were constructed. The C-index and calibration curves were used to evaluate the performance of the model. Overall survival (OS) curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare OS differences between groups. Propensity score matching (PSM) was performed to reduce bias. A total of 12 610 NSCLC patients with M1 category (N0 group: 3045 cases; N1-3 group: 9565 cases) were included. Regarding the N0 group, multivariate analysis demonstrated that age, sex, race, surgery, grade, tumor size, and M category were independent prognostic factors. A nomogram and corresponding risk-classifying systems were formulated. Favorable validation results were obtained from the C-index, calibration curves, and survival comparisons. Survival curves demonstrated that N0 NSCLC patients had better survival than N1-3 NSCLC patients both before and after PSM. Furthermore, the survival of resected N0M1 patients was superior to that of those without surgery. In this study, a prognostic nomogram and risk-classifying systems designed for the T1-4N0M1 NSCLC patients showed acceptable performance. Primary lung tumor resection might be a feasible treatment for this population subset. Additionally, we proposed that lymph node stage might have a place in the forthcoming tumor-node-metastasis (TNM)staging proposal for NSCLC patients with M1 category.

CT-Based Screening for Pulmonary Metastases in Head and Neck Squamous Cell Cancers: Diagnostic Accuracy and Cost Comparison with PET-CECT.

This study's objective was to compare detection rates of radiograph, computed tomography (CT), and positron emission tomography-contrast-enhanced computed tomography (PET-CECT) for pulmonary metastasis/synchronous primary lung tumors in head and neck squamous cell cancer (HNSCC) and its association with clinico-radio-pathological factors. Our retrospective study included 837 HNSCC patients from January 2012 to December 2017. Lung nodules were characterized on CT as benign, indeterminate, and metastatic. The true detection rate and statistical significance of associated risk factors were calculated. Risk factors for metastasis were determined using univariate and multivariate logistic regression models. Seventy-five (8.9%) patients had pulmonary metastasis and 3 (0.3%) had second lung primary. Detection rate of pulmonary metastasis by CT was higher (sensitivity-97.3%, specificity-97.2%) as compared to radiograph (sensitivity 49% and specificity 89%). Correlation was found between pulmonary and extra-pulmonary metastasis and N classification (P = 0.01, P = 0.02) and positive low jugular node (P = 0.001, P = 0.001). Using PET-CECT in place of CT costed an extra outlay of 7,033,805 INR (95,551.85 USD) while detecting distant metastasis in only 4 (0.47%) extra cases. Chest CT is a useful pulmonary metastases screening tool in advanced HNSCC patients with reasonable imaging cost as compared to PET-CT.

Cerebrospinal fluid as a liquid biopsy for molecular characterization of brain metastasis in patients with non-small cell lung cancer

ObjectivesNon-small cell lung cancer (NSCLC) with brain metastases (BM) is a challenging clinical issue with poor prognosis. No data exist regarding extensive genetic analysis of cerebrospinal fluid (CSF) and its correlation to associated tumor compartments. Materials and MethodsWe designed a study across multiple NSCLC patients with matched material from four compartments; primary tumor, BM, plasma and CSF. We performed enrichment-based targeted next-generation sequencing analysis of ctDNA and exosomal RNA in CSF and plasma and compared the outcome with the solid tumor compartments. ResultsAn average of 105 million reads per sample was generated with fractions of mapped reads exceeding 99% in all samples and with a mean coverage above 10,000x. We observed a high degree of overlap in variants between primary lung tumor and BM. Variants specific for the BM/CSF compartment included in-frame deletions in AR, FGF10 and TSC1 and missense mutations in HNF1a, CD79B, BCL2, MYC, TSC2, TET2, NRG1, MSH3, NOTCH3, VHL and EGFR. ConclusionOur approach of combining ctDNA and exosomal RNA analyses in CSF presents a potential surrogate for BM biopsy. The specific variants that were only observed in the CNS compartments could serve as targets for individually tailored therapies in NSCLC patients with BM.

Stereotactic body radiotherapy for extra-cranial oligoprogressive or oligorecurrent small-cell lung cancer.

The role of local ablative treatments, including stereotactic body radiotherapy (SBRT), is an area of active research in oligometastatic patients. Small cell lung cancer (SCLC) has a poor prognosis, with common diffuse metastatic evolution. We evaluated the outcomes after SBRT in uncommon oligoprogressive/oligorecurrent SCLC presentation. Data of SCLC patients who received SBRT for oligoprogressive/oligorecurrent metastatic disease at four centers were retrospectively analyzed. Patients with synchronous oligometastatic disease, SBRT for primary lung tumor and brain radiosurgery were not included. Relapse and survival rates were defined as the time between the date of SBRT and the first event. Twenty patients (60% with initially limited-disease [LD]) presenting 24 lesions were identified. Oligoprogression and oligorecurrence were observed in 6/20 (30%) and 14/20 (70%) patients, respectively. SBRT was delivered to one (n=16) to two (n=4) lesions (median size, 26mm), mainly to lung [n=17/24] metastases. At a median follow-up of 2.9years, no local relapse was observed and 15/20 patients experienced a distant relapse (DR). The median DR and OS were 4.5months (95%CI: 2.9-13.7months) and 17.2months (95%CI: 7.5-65.2months), respectively. The 3-year distant control and OS rates were 25% (95 %CI: 6-44%) and 37% (95 %CI: 15-59%), respectively. Initial LD (vs extensive-disease) was the only prognosis factor associated with a lower risk of post-SBRT DR (HR: 0.3; 95% CI: 0-0.88; p=0.03). There was no severe observed SBRT-related toxicities. Prognosis was poor, with DR occurring in most patients. However, local control was excellent and long term response after SBRT may rarely occur in patients with oligoprogressive/oligorecurrent SCLC. Local ablative treatments should be discussed in a multidisciplinary setting on well-selected cases.

Central Nervous System tumor at “Prof. Dr. I.G.N.G. Ngoerah” General Hospital, Denpasar: An epidemiological study between 2020-2022

Background. Central Nervous System (CNS) tumor is neoplasm that located in central nervous system, which include brain and medulla spinalis. Despite its significant raise of incidence and morbidities, limited epidemiological data was available. Therefore, this study aimed to describe the epidemiological characteristic of CNS tumor over a 3-year period in a single tertiary hospital in Bali, Indonesia. Methods. This study was a descriptive study with cross sectional design. This study included all patients aged 18 year or over who were histopathologically diagnosed with central nervous tumor at “Prof. Dr. I.G.N.G. Ngoerah General Hospital”, Denpasar, between January 2020 and December 2022. Data about age, gender, tumor location, histopathological type, tumor grading, and source of metastases in secondary CNS tumor were obtained from medical record. Result. A total of 221 cases were recorded during this study period. The prevalence of primary CNS tumor was 81.9% while secondary CNS tumor was 18.1%. The majority of case, both in primary and secondary CNS tumor were female in age group of 50-59. Supratentorial constituted the most common lesion site in primary and secondary CNS tumor. The most frequent histopathological type of primary CNS tumor was meningioma, making up 48.1% of cases, followed by diffuse astrocytic and oligodendroglial tumors (26.5%), and tumor of the cranial and paraspinal nerve (9.9%). Carcinoma is the most common histological type in secondary CNS tumor with lung and breast tumor being the majority source of secondary CNS tumor, found in 40% and 27.5%, respectively. Conclusion. Adult female with age of 50-59 is the most affected group in CNS tumor. Primary CNS tumor were commonly found in supratentorial with meningioma and WHO grade I being the most frequent histopathological type and grade. Secondary CNS tumor were mostly found in supratentorial and originated from primary lung tumor.

A Case Report on the Improvement of Cancer Pain in a Patient with Metastatic Non-Small Cell Lung Cancer Through Herbal Medicine-based Integrative Cancer Treatment with Chemotherapy

Objective: To demonstrate an improvement in metastatic cancer pain and a decrease in tumor size in a patient with non-small cell lung cancer.Method: A 53-year-old female patient diagnosed with metastatic non-small cell lung cancer in August 2022 underwent integrative cancer treatment (ICT) for two months to decrease the tumor size and improve back pain from bone metastasis. The patient underwent chemotherapy with ICT. Radiologic outcomes were assessed by chest, abdomen, and pelvis computed tomography based on the Response Evaluation Criteria in Solid Tumors (RECIST) protocol. Clinical outcomes were assessed using National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE), Eastern Cooperative Oncology Group (ECOG), and a numeric rating scale (NRS).Result: During the two months of treatment, the NRS scores for back pain were improved, and the ECOG score improved from grade 2 to 1. The size and metabolic activity of the primary lung tumor decreased and underwent partial remission based on RECIST. No serious side effects of grade 3 or higher were noted on the NCI-CTCAE test.Conclusion: This case suggests that ICT may have a therapeutic effect for cancer pain and a synergetic effect with chemotherapy for metastatic non-small cell lung cancer.