SALTT study: A retrospective analysis of 111 SAlivary gland tumors of Lung and Tracheobronchial Tree.

INTRODUCTION: Primary pulmonary salivary gland-type tumours (PPSGT) are rare lung neoplasms arising from submucosal seromucinous glands in the central airway. METHODS AND RESULTS: We retrospectively analysed the clinicopathological features of 111 PPSGTs diagnosed at our institute between 2003 and 2021. The mean age at diagnosis was 43.8 years(range 6-78 years) and a male-to-female ratio of 2:1. On imaging, 92 % of cases had centrally located tumours and 37.3 % were early stage. The histopathological types included 70 cases (63 %) of mucoepidermoid carcinoma (MEC), 31 cases (27.7 %) of adenoid cystic carcinoma (ADCC), two cases of myoepithelial carcinoma, one case each of acinic cell carcinoma (ACC), clear cell carcinoma (CCC), epithelial myoepithelial carcinoma (EMC) and 5 others [including adenocarcinoma of minor salivary gland origin(n = 3), carcinoma with sebaceous differentiation(n = 1) and poorly differentiated carcinoma of salivary gland type(n = 1)]. The size of the tumours found in the resection specimens ranged from 1 cm to 13 cm, with an average size of 4.9 cm. High-risk attributes such as lymphovascular invasion (LVI), perineural invasion (PNI), pleural involvement, positive resection margins, and nodal metastasis were identified in 15.3 %, 15.3 %, 13.6 %,15.2 % and 6.7 % of cases, respectively. These attributes were found to be more frequent in ADCC than in MEC. Surgery was the main treatment modality [68/84 (80 %) cases]. ADCC cases had more recurrence and distant metastasis than MEC cases. The 3- year overall-survival (OS) and recurrence-free survival(RFS) were better in patients with age lesser than 60 years(p-value <0.0001), low pT stage (p-value 0.00038) and lower grade of MEC(p-value-0.0067). CONCLUSION: It is crucial to have an acquaintance with the morphologic spectrum and immunophenotypic characteristics of PPSGT to recognize them in this unusual location. In tandem, it is crucial to differentiate them from conventional primary non-small cell lung carcinoma, as the management protocols and prognostic implications differ significantly.

Deep-Learning-Based Predictive Imaging Biomarker Model for EGFR Mutation Status in Non-Small Cell Lung Cancer from CT Imaging.

PURPOSE: The authors aimed to develop and validate deep-learning-based radiogenomic (DLR) models and radiomic signatures to predict the EGFR mutation in patients with NSCLC, and to assess the semantic and clinical features that can contribute to detecting EGFR mutations. METHODS: Using 990 patients from two NSCLC trials, we employed an end-to-end pipeline analyzing CT images without precise segmentation. Two 3D convolutional neural networks segmented lung masses and nodules. RESULTS: The combined radiomics and DLR model achieved an AUC of 0.88 ± 0.03 in predicting EGFR mutation status, outperforming individual models. Semantic features further improved the model's accuracy, with an AUC of 0.88 ± 0.05. CT semantic features that were found to be significantly associated with EGFR mutations were pure solid tumours with no associated ground glass component (p < 0.03), the absence of peripheral emphysema (p < 0.03), the presence of pleural retraction (p = 0.004), the presence of fissure attachment (p = 0.001), the presence of metastatic nodules in both the tumour-containing lobe (p = 0.001) and the non-tumour-containing lobe (p = 0.001), the presence of ipsilateral pleural effusion (p = 0.04), and average enhancement of the tumour mass above 54 HU (p < 0.001). CONCLUSIONS: This AI-based radiomics and DLR model demonstrated high accuracy in predicting EGFR mutation, serving as a non-invasive and user-friendly imaging biomarker for EGFR mutation status prediction.

Trastuzumab Plus Gemcitabine-Cisplatin for Treatment-Naïve Human Epidermal Growth Factor Receptor 2-Positive Biliary Tract Adenocarcinoma: A Multicenter, Open-Label, Phase II Study (TAB).

PURPOSE: Human epidermal growth factor receptor 2 (HER2) overexpression is seen in 4%-16% of biliary tract cancers (BTCs). We aimed to evaluate the clinical activity of gemcitabine-cisplatin (GC) plus anti-HER2 antibody trastuzumab as initial treatment in HER2-positive BTCs. METHODS: This study was an investigator-initiated, open-label, single-arm, multi-institutional, phase II trial in adult patients with HER2-positive (defined as immunohistochemistry [IHC] 3+ or IHC 2+ and fluorescent in situ hybridization-positive), treatment-naïve BTCs. The primary end point of the study was 6-month progression-free survival (PFS). Next-generation sequencing was performed on tissue samples to evaluate mutational status. RESULTS: From March 2020 to August 2022, of the 876 screened patients, 118 (13.4%) were found to have HER2-positive status, of whom 90 were enrolled in the study. Most patients had GBC (n = 96; 96%) with two or more sites of metastatic disease (n = 70; 78%). With a median follow-up of 17.3 (95% CI, 15.22 to 19.32) months, 72 patients had disease progression with a median PFS of 7 (95% CI, 6.2 to 7.8) months. The diagnosis to event 6-month PFS rate was 75.6% (95% CI, 66.6 to 84.6). A complete or partial response was seen in 50 (55.5%) patients and 22 (24.4%) patients had stable disease as the best response to treatment, for an overall disease control rate of 80%. The presence of isolated TP53 mutations was associated with inferior PFS compared with other mutations (TERT promoter, HER2, PIK3CA, etc) or no detected mutations (6.51 v 12.02 v 10.58 months; P < .001). CONCLUSION: The combination of GC and trastuzumab achieved its primary end point of improving PFS compared with historical data in the treatment-naïve HER2-positive BTC. Evaluating additional mutations such as TP53 and PIK3CA along with HER2 testing may help to preferentially select patients for anti-HER2 therapy in the future (Clinical Trial Registry India number: CTRI/2019/11/021955).

Cross-sectional imaging review of common to uncommon lung cancer mimickers in a tertiary care oncology center.

Lung cancer is the most diagnosed cancer worldwide. Many non-malignant pulmonary lesions, such as tuberculosis, fungal infection, organizing pneumonia, inflammatory myofibroblastic tumor, and IgG4 disease, can mimic lung cancer due to their overlapping morphological appearance on imaging. These benign entities with minor differentiating imaging clues may go unnoticed in a high-volume cancer institution, leading to over-investigation that may result in repeated biopsies, pointless wedge resections, and related morbidities. However, with a thorough medical history, laboratory diagnostic work-up, and careful analysis of imaging findings, one can occasionally restrict the range of possible diagnoses or arrive at a definitive conclusion. When imaging features overlap, image-guided lung sampling is crucial since histopathological analysis is the gold standard.

Rapid on-site evaluation (ROSE) versus macroscopic on-site evaluation (MOSE) for endoscopic ultrasound-guided sampling of solid pancreatic lesions: a paired comparative analysis using newer-generation fine needle biopsy needles.

Background: Rapid on-site examination (ROSE) during endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) has been a subject of debate. We compared the yield of EUS-FNB with adequacy assessed using macroscopic on-site evaluation (MOSE), and smear cytology with adequacy confirmed by ROSE, acquired using the same needle. Methods: Consecutive patients with solid pancreatic lesions (SPLs) who underwent EUS-FNB of pancreatic solid lesions between January 2021 and July 2022 were included. Demographic details, site and size of lesion, number of passes, and the diagnosis by cytology and histopathology of core tissue were noted. The first pass was used for ROSE adequacy assessment and was subsequently sent for cytological assessment. Additional passes were taken subsequently to acquire core tissue. Adequacy was confirmed by MOSE (whitish core of more than 4 mm). Final cytology and histopathology (HPE) were compared for diagnostic accuracy. Results: One hundred fifty-five patients were included in the analysis during the study period (mean age 55.1+12.9 years; 60% male; 77% in pancreatic head; median size 3.7 cm). The final diagnosis was malignancy in 129, while 26 were negative for malignancy. Sensitivity and specificity for ROSE with cytology in detecting malignant SPLs were 96.9% and 100%, respectively. HPE with MOSE had sensitivity and specificity of 96.1% and 100%, respectively. A comparison of diagnostic accuracy showed no significant difference (P>0.99) between HPE with MOSE and ROSE with cytology, using an FNB needle. Conclusion: MOSE is as good as ROSE in terms of diagnostic yield for solid pancreatic lesions sampled using newer-generation EUS biopsy needles.

Validation of Remote Digital Pathology based diagnostic reporting of Frozen Sections from home.

Background: Despite the promising applications of whole-slide imaging (WSI) for frozen section (FS) diagnosis, its adoption for remote reporting is limited. Objective: To assess the feasibility and performance of home-based remote digital consultation for FS diagnosis. Material & Method: Cases accessioned beyond regular working hours (5 pm-10 pm) were reported simultaneously using optical microscopy (OM) and WSI. Validation of WSI for FS diagnosis from a remote site, i.e. home, was performed by 5 pathologists. Cases were scanned using a portable scanner (Grundium Ocus®40) and previewed on consumer-grade computer devices through a web-based browser (http://grundium.net). Clinical data and diagnostic reports were shared through a google spreadsheet. The diagnostic concordance, inter- and intra-observer agreement for FS diagnosis by WSI versus OM, and turnaround time (TAT), were recorded. Results: The overall diagnostic accuracy for OM and WSI (from home) was 98.2% (range 97%-100%) and 97.6% (range 95%-99%), respectively, when compared with the reference standard. Almost perfect inter-observer (k = 0.993) and intra-observer (k = 0.987) agreement for WSI was observed by 4 pathologists. Pathologists used consumer-grade laptops/desktops with an average screen size of 14.58 inches (range = 12.3-17.7 inches) and a network speed of 64 megabits per second (range: 10-90 Mbps). The mean diagnostic assessment time per case for OM and WSI was 1:48 min and 5:54 min, respectively. Mean TAT of 27.27 min per case was observed using WSI from home. Seamless connectivity was observed in approximately 75% of cases. Conclusion: This study validates the role of WSI for remote FS diagnosis for its safe and efficient adoption in clinical use.

Epidemiological Trend of Esophageal Cancer at a Tertiary Cancer Center in Mumbai, India, Over the Past 15 Years.

BACKGROUND: In developed countries, there has been a definite change in the histopathological spectrum of esophageal cancer towards adenocarcinoma. There are limited data from India regarding the histopathological profile of patients with esophageal cancer. MATERIALS AND METHODS: We retrospectively evaluated patients with histologically proven esophageal cancer who were registered at the Tata Memorial Hospital (Mumbai, India) between 2003 and 2018. The primary aim of the study was to analyze the time-trend of the histological pattern of esophageal cancer. Our secondary objectives included evaluating whether there was any correlation between the histology of the esophageal cancer and the age, sex, socioeconomic status (the paying ability of the patient, which was reflected in the treatment category of the patient, i.e., private [full payment], general [subsidized payment], or no charge), comorbidities, and a history of substance abuse. RESULTS: Among 7874 patients with esophageal cancer, 5092 (64.7%) were men, with a male-to-female ratio of 1.8:1. The median age was 57 years (IQR, 50-65). Of the 4912 patients in whom a history of tobacco or alcohol use had been elicited, 1360 (27.7%) had no history of substance abuse. A majority of the tumors (2942, 37.4%) originated in the middle-third of the esophagus. Squamous cell carcinoma was the predominant histological type, noted in 6413 (81.4%) patients and remained the most common histologic type consistently through the study with no evidence of a time-trend in the histological pattern. On the multivariate analysis, female sex and a history of substance abuse were associated with higher odds of squamous cell carcinoma, while the presence of comorbidities and lower esophageal/gastroesophageal junction primaries were associated with higher odds of adenocarcinoma. CONCLUSIONS: There is no evidence of an epidemiological shift in the histopathologic spectrum of esophageal cancer in India over the last two decades. Four out of five Indian patients with esophageal cancer have squamous cell histology, with the commonest site of origin being the middle third. This is important to recognize, given the varying molecular spectrum and efficacy of therapeutic modalities based on histopathology.

Safety, toxicity and pharmacokinetic assessment of oral Withaferin-A in mice.

Withaferin-A (WA) is the principle component of Withania somnifera (Ashwagandha). It has several biological activities including anti-cancer, anti-diabetic, neuroprotective, hepatoprotective and immune-modulatory properties. The acute and sub-acute toxicity of oral WA was investigated in mice. In the acute toxicity study, up to 2000 mg/kg of WA was well tolerated without any signs of toxicity or death. In the sub-acute toxicity study, mice were orally administered 10, 70 and 500 mg/kg of WA respectively, daily for 28 days. Upon physiological, serum chemistry, hematology and histopathogical examination, no features suggestive of drug-induced toxicity were observed at any dose levels, thereby confirming the No-Observed Adverse Effect Level (NOAEL) to be at least 500 mg/kg. Furthermore, the oral bioavailability of WA was evaluated using single intravenous and oral doses of 10 mg/kg and 70 mg/kg respectively using sparse sampling strategy. Bioanalysis was carried out using a validated LC-MS/MS method. The AUC of WA was found to be 3996.9 ± 557.6 ng/mL*h and 141.7 ± 16.8 ng/mL*h for the intravenous and oral routes of administration respectively. The oral bioavailability was determined to be 1.8%. To conclude, WA was found to be extremely safe even at high doses, with a low oral bioavailability.

Characteristics and clinical outcomes of pulmonary sarcomatoid carcinoma: experience from Tata Memorial Centre.

Background: Pulmonary sarcomatoid carcinoma (PSC) constitutes a heterogeneous group of poorly differentiated non-small cell lung cancers. Since these are rare tumours, we sought to determine the characteristics and clinical outcomes of these patients treated at our centre. Methods: We did a retrospective evaluation of all patients diagnosed with PSC between January 2013 and September 2020 at the Tata Memorial Hospital, Mumbai, India. Baseline demographic and treatment data and outcomes were obtained retrospectively from electronic medical records and survival was calculated by using the Kaplan-Meier method. Results: Out of 151 patients diagnosed with PSC during this period, 129 were included in the final analysis. The clinical stage was stage I in 3 (2.03%), stage II in 4 (3.1%), stage III in 35 (27.1%) and stage IV in 87 (67.4%). The median follow-up duration was 32 months (range, 15.0-48.9). The median overall survival (OS) of patients who received curative surgery was 18 months (95% confidence interval (95% CI), 2.59-33.4); concurrent chemoradiation was 11 months (95% CI, 2.99-19); palliative chemotherapy was 8 months (95% CI, 5.24-10.75) and best supportive care was 1 month (95% CI, 0.43-1.57, p = 0.001). On multivariate analysis, the presence of brain metastasis (p = 0.018; hazard ratio (HR), 2.47; 95% CI, 1.34-4.49) and the administration of chemotherapy (p = 0.037; HR, 2.2; 95% CI, 1.04-4.94) were the only factors impacting the OS. Conclusion: PSC usually presents in advanced stages and is associated with a poor prognosis.

Validation of a Portable Whole-Slide Imaging System for Frozen Section Diagnosis.

BACKGROUND: Frozen section (FS) diagnosis is one of the promising applications of digital pathology (DP). However, the implementation of an appropriate and economically viable DP solution for FS in routine practice is challenging. The objective of this study was to establish the non-inferiority of whole-slide imaging (WSI) versus optical microscopy (OM) for FS diagnosis using a low cost and portable DP system. MATERIALS AND METHODS: A validation study to investigate the technical performance and diagnostic accuracy of WSI versus OM for FS diagnosis was performed using 60 FS cases[120 slides i.e, 60 hematoxylin and eosin (H & E) and 60 toluidine blue (TOLB)]. The diagnostic concordance, inter- and intra-observer agreement for FS diagnosis by WSI versus OM were recorded. RESULTS: The first time successful scanning rate was 89.1% (107/120). Mean scanning time per slide for H and E and TOLB slide was 1:47 min (range; 0:22-3: 21 min) and 1:46 min (range; 0:21-3: 20 min), respectively. Mean storage space per slide for H and E and TOLB slide was 0.83 GB (range: 0.12-1.73 GB) and 0.71 GB (range: 0.11-1.66 GB), respectively. Considering major discrepancies, the overall diagnostic concordance for OM and WSI, when compared with the reference standard, was 95.42% and 95.83%, respectively. There was almost perfect intra as well as inter-observer agreement (k ≥ 0.8) among 4 pathologists between WSI and OM for FS diagnosis. Mean turnaround time (TAT) of 14:58 min was observed using WSI for FS diagnosis, which was within the College of American Pathologists recommended range for FS reporting. The image quality was average to best quality in most of the cases. CONCLUSION: WSI was noninferior to OM for FS diagnosis across various specimen types. This portable WSI system can be safely adopted for routine FS diagnosis and provides an economically viable alternative to high-end scanners.