Browsing by Author "Maniar, Rohan"

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    AB018. Local recurrence of thymoma following minimally invasive resection: a retrospective case series
    (AME, 2023-12-30) Davis, Hannah O.; Heldman, Emily M.; Laniak, Louis J.; Wuthrich, Brice S.; Badve, Sunil S.; Mesa, Hector A.; Kesler, Kenneth A.; Maniar, Rohan; Loehrer, Patrick J.; Pathology and Laboratory Medicine, School of Medicine
    Background: Surgery remains the mainstay treatment for non-metastatic thymic epithelial tumors (TETs) and has traditionally been performed via an open approach. Minimally invasive techniques have gained popularity with the aim of decreasing postoperative morbidity. However, there is concern that these techniques could increase the risk of local relapse. We undertook a retrospective institutional review of thymoma patients presenting for evaluation of local disease after surgery utilizing minimally invasive approaches. Methods: A database of TET patients evaluated at Indiana University from 1997 to 2022 was queried. From this database, we identified and reviewed 19 thymoma patients who underwent minimally invasive surgery and subsequently developed local recurrence. Results: The median age in this cohort was 46 years (range, 14–70 years) and included 9 female and 10 male patients. At the time of initial surgery, the distribution of stages was I (n=5), II (n=10), and III (n=3) and WHO histologic classifications were A/AB (n=3) and B1-3 (n=15); one patient’s initial pathology could not be determined. The median tumor size was 6.2 cm (range, 3–10.2 cm). Seventeen patients were operated on at outside institutions, while two had their surgeries at Indiana University. Surgical approaches included unilateral video-assisted thoracic surgery (VATS) (n=7), unilateral robot-assisted thoracic surgery (RATS) (n=8), bilateral VATS (n=2), and the Chamberlain procedure (n=2). Fifteen patients had R0 resections, while 4 had microscopic positive surgical margins (R1). Seven patients received adjuvant radiation therapy. All patients had pleural recurrence ipsilateral to the surgical approach. Ten patients also had mediastinal recurrence; 8 of whom had R0 resection during the initial surgery. The median time to recurrence was 31 months (range, 6–130 months). Conclusions: Our cohort of patients who presented for evaluation of thymoma recurrence after a minimally invasive surgical approach had median tumor size greater than 5 cm and higher World Health Organization (WHO) classifications. Relapses were identified as late as 10 years following surgery. While it remains unclear whether local recurrence was related to dissemination during surgery, the finding of ipsilateral pleural space relapse in all cases is strongly suggestive. This case series demonstrates the need for carefully controlled studies and long-term follow-up to determine optimal surgical approaches for thymoma.
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    AB025. Evaluation of potential therapeutic immunohistochemical targets with experimental or FDA-approved therapies in thymic epithelial tumor microarrays
    (AME, 2023-12-30) Ardeshir-Larijani, Fatemeh; Loehrer, Patrick J.; Maniar, Rohan; Hou, Tieying; DeBrock, Victoria; Mesa, Hector; Pathology and Laboratory Medicine, School of Medicine
    Background: Thymus epithelial tumors (TETs) are rare malignancies of the anterior mediastinum. The current standard of care for metastatic TETs is a combination of platinum-based chemotherapy. Here, we have evaluated the experimental and FDA-approved makers in a large TET tissue array with the hope of identifying a new therapeutic option. Methods: A tissue microarray (TMA) containing ninety malignant thymic tumors (A, AB, B1 and B2, n=62, B2/B3 and B3, n=16, and thymic carcinoma, n=12) and seven normal adult thymus were assembled. The protein expressions of GLUT1, TROP2, PSMA, ROS1, ALK, HER2, and PDL-1 were tested with immunohistochemical assays. Expression was quantified using a “staining score (SS)”, which is a 0–3 numerical score that results from the product of the intensity of expression: 0= negative, 1= weak, 2= moderate, 3= strong, and the area of expression in fractions of a percent (0= no expression, 1= 100% area). Expression of HER2 and PDL-1 was quantified according to existing guidelines [HER2 score and combined positive score (CPS)]. Results: Trop-2 had the highest expression in thymic carcinoma (TC) (100%, SS 2.6±0.6) followed by thymoma B2/B3 (78%, SS 1.3±1.3), types A/AB/B1 (54%, SS 1.1±1.1) (P=0.01). In TC, all patients with squamous histology had immunohistochemistry (IHC) SS of 3. Patients with thymoma who had Trop-2 expression experienced significantly worse survival [hazard ratio (HR): 3.3, P=0.008]. GLUT1 was highly expressed in TC (81.8%, SS: 2.1±1, TC vs. normal thymus, P=0.0003). PDL-1 was expressed in all TET tissues (mean, 2.5–52 CPS). No significant expression of ALK, ROS1, or HER2 observed in normal thymus or TETs. Conclusions: Trop-2 expression is a prognostic marker in TETs. High expression of Trop-2 protein in thymoma and TC appears a promising therapeutic target for Trop-2 antibody-drug conjugates.
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    Management of stage IVA (M1a) thymoma: observation versus chemotherapy versus surgery versus radiation therapy?—extended abstract
    (AME, 2024-05-27) Kesler, Kenneth A.; Maniar, Rohan; Loehrer, Patrick J.; Surgery, School of Medicine
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    Metabolic Interplay in the Tumor Microenvironment: Implications for Immune Function and Anticancer Response
    (MDPI, 2023-12-05) Youssef, Reem; Maniar, Rohan; Khan, Jaffar; Mesa, Hector; Pathology and Laboratory Medicine, School of Medicine
    Malignant tumors exhibit rapid growth and high metabolic rates, similar to embryonic stem cells, and depend on aerobic glycolysis, known as the "Warburg effect". This understanding has enabled the use of radiolabeled glucose analogs in tumor staging and therapeutic response assessment via PET scans. Traditional treatments like chemotherapy and radiotherapy target rapidly dividing cells, causing significant toxicity. Despite immunotherapy's impact on solid tumor treatment, gaps remain, leading to research on cancer cell evasion of immune response and immune tolerance induction via interactions with the tumor microenvironment (TME). The TME, consisting of immune cells, fibroblasts, vessels, and the extracellular matrix, regulates tumor progression and therapy responses. TME-targeted therapies aim to transform this environment from supporting tumor growth to impeding it and fostering an effective immune response. This review examines the metabolic disparities between immune cells and cancer cells, their impact on immune function and therapeutic targeting, the TME components, and the complex interplay between cancer cells and nontumoral cells. The success of TME-targeted therapies highlights their potential to achieve better cancer control or even a cure.
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    What Have We Learned from Molecularly Informed Clinical Trials on Thymomas and Thymic Carcinomas-Current Status and Future Directions?
    (MDPI, 2024-01-18) Maniar, Rohan; Loehrer, Patrick J.; Medicine, School of Medicine
    Thymic epithelial tumors (TETs), which include thymomas and thymic carcinomas, are a rare, heterogeneous group of malignancies that originate from the thymus gland. As an important organ of immune cell development, thymic tumors, particularly thymomas, are often associated with paraneoplastic autoimmune disorders. The advances in targeted therapies for both solid and hematologic malignancies have resulted in improved patient outcomes, including better and more durable efficacy and improved toxicity. Targeted therapies have also been investigated in the treatment of TETs, though the results have largely been modest. These have included somatostatin-receptor-targeting therapies, KIT- and EGFR-directed tyrosine kinase inhibitors, epigenetic modulators, anti-angiogenesis agents, and agents targeting the cell proliferation and survival pathways and cell cycle regulators. Numerous investigated treatments have failed or underperformed due to a lack of a strong biomarker of efficacy. Ongoing trials are attempting to expand on previous experiences, including the exploration of effective drugs in early-stage disease. Novel combination therapy strategies are also undergoing evaluation, with the goal of augmenting efficacy and understanding the toxicity while expanding the biomarkers of efficacy and safety. With advances in technology to improve target identification and drug delivery, old targets may become new opportunities, and the subsequently developed drugs may find their place in the treatment of thymic tumors.