Mediastinal Research Articles

Anaesthesia and Airway Challenges in Patients with Corrosive Pharyngo-oesophageal Stricture: Experience of a Tertiary Care Centre

Background: Ingestion of corrosive substances causes necrosis of the tissues of the upper airway and upper gastrointestinal tract resulting not only in acute airway injuries but also long-term sequelae like strictures. Medical and surgical management of these strictures has been discussed extensively; however, there is little literature available on the anaesthetic management of pharyngo-oesophageal strictures. We hereby discuss our experience in managing these patients undergoing surgical correction. Methods: Out of a total of 57 cases of corrosive ingestion injuries between 2008 and 2016, medical records of 15 patients with complex pharyngeal or high oesophageal strictures undergoing surgical intervention were reviewed. The preoperative findings, the extent of airway involvement and any airway intervention done were noted. Based on the surgical intervention, patients were divided into two groups; Group A included patients undergoing repeated string dilatation and Group B included those undergoing coloplasty. Type of anaesthesia given, details of airway management, intraoperative and postoperative course and complications were noted. Results: Group A consisted of 10 patients who underwent endless string dilatation, and Group B consisted of five patients who underwent coloplasty. In Group A, general anaesthesia with endotracheal intubation was given to all patients except for one patient who was tracheostomised. Two patients had significant glottic narrowing and required a smaller size tube. In Group B, four out of five patients were tracheostomised, while one had a normal glottic opening. General anaesthesia with epidural analgesia was given to all patients. Severe haemodynamic changes were seen during tunnelling through the posterior mediastinum for colonic interposition. All patients were extubated on the table. None of the patients required postoperative ventilatory or inotropic support. Conclusion: Management of corrosive pharyngo-oesophageal strictures is challenging and requires a multidisciplinary approach. Careful assessment and management of the airway, vigilant intraoperative haemodynamic monitoring and good pain management are the key contributions of anaesthesia care.

Ectopic Thyroid Tissue Presenting as a Superior Mediastinum Mass in a Patient with Normal Thyroid Gland

Ectopic Thyroid Tissue Presenting as a Superior Mediastinum Mass in a Patient with Normal Thyroid Gland

Postoperative Radiotherapy in Curatively Resected Esophageal Squamous Cell Carcinoma With Occult Recurrent Laryngeal Nerve Lymph Node Metastasis.

Surgery is the mainstream treatment for early-stage esophageal squamous cell carcinoma (ESCC) and occult recurrent laryngeal nerve lymph node metastasis (RLNM) is not uncommon among those with R0 resection. The clinical value of postoperative radiotherapy (PORT) in patients with RLNM only is still controversial. Consecutive patients with early-stage ESCC treated with R0 resection and pathologically confirmed RLNM only from June 2012 to July 2022 were retrospectively reviewed. PORT, covering the supraclavicular and superior mediastinum area (small T-field) at a dose of 50.4Gy for 28 fractions, was performed in some patients. Propensity score matching (PSM) was performed to balance the baseline characteristics between patients with or without PORT. Pattern of failure, disease-free survival (DFS), and overall survival (OS) were compared. Among the 189 patients identified, 69 (35.5%) received PORT and the other 120 (63.5%) did not. After PSM, 154 patients were included in the matched cohort, including 62 in the PORT group and 92 in the non-PORT group. With a median follow-up of 48 (95% CI: 40.3-55.7) months, 69 patients developed their initial disease recurrence in the whole population and PORT significantly decreased the frequency of local recurrence (61.2% vs 21.4%) among those with recurrent disease. Additionally, in the PSM matched cohort, PORT significantly prolonged patients' DFS (HR 0.393, P = 0.002) and OS (HR 0.462, P = 0.020). Moreover, PORT remained as the independent factor associated with improved DFS (HR 0.360, P = 0.001) and OS (HR 0.451, P = 0.021) after multivariate Cox analyses. In addition, tumor location and pathological TNM stage were found to be independent prognostic factors associated with survival outcomes. PORT is associated with improved DFS and OS in ESCC patients with R0 resection and RLNM only, which warrants future validation.

Kiosk 4Q-TA-07 - Multimodality Imaging and Surgical Considerations of a Posterior Mediastinal Mass

Kiosk 4Q-TA-07 - Multimodality Imaging and Surgical Considerations of a Posterior Mediastinal Mass

Implementation of an Anterior Mediastinal Mass Pathway to Improve Time to Biopsy and Multidisciplinary Communication.

Mediastinal masses in children with cancer present unique challenges, including the risk of respiratory and hemodynamic compromise due to the complex anatomy of the mediastinum. Multidisciplinary communication is often a challenge in the management of these patients. After a series of patients with mediastinal masses were admitted to Riley Hospital for Children Pediatric Intensive Care Unit, the time from presentation to biopsy and pathology was greater than expected. We aimed to reduce the time to biopsy by 25% and demonstrate improved multidisciplinary communication within 6 months of protocol implementation for patients presenting to Riley Hospital for Children Emergency Department with an anterior mediastinal mass. Quality improvement methodology created a pathway that included early multidisciplinary communication. The pathway includes communication between the emergency department and multiple surgical and medical teams via a HIPPA-compliant texting platform. Based on patient stability, imaging findings, and sedation risks, the approach and timing of the biopsy were determined. The pathway has been used 20 times to date. We successfully reduced the time to biopsy by 38%, from 25.1 hours to 15.4 hours. There was no statistically significant reduction in time to pathology. The multidisciplinary team reported improved communication from a baseline Likert score of 3.24 to 4. By initiating early multidisciplinary communication, we reduced the time to biopsy and pathology results, improving care for our patients presenting with anterior mediastinal masses.

Endobronchial Ultrasound-Guided Transbronchial Mediastinal Cryobiopsy versus Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for Mediastinal Disorders: A Meta-Analysis

Introduction: Endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy (EBUS-TMC), a novel technique, has been reported to improve the diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for mediastinal lesions in recent studies. Current literature suggests that this procedure has greater diagnostic efficacy compared to conventional EBUS-TBNA. This systematic review and meta-analysis aimed to evaluate the diagnostic yield and complications associated with EBUS-TMC in comparison to EBUS-TBNA, thereby exploring the potential of this novel technique in enhancing the diagnostic utility for mediastinal lesions. Methods: A comprehensive literature review was conducted by searching the PubMed, Embase, and Google Scholar databases for articles published from inception to December 31, 2023. The objective of this review was to evaluate the utilization of EBUS-TMC in diagnosing mediastinal disease, while also assessing the quality of each study using the QUADAS-2 tool. The diagnostic yield estimates were subjected to a meta-analysis utilizing inverse variance weighting. Furthermore, a comprehensive analysis of the complications associated with this procedure was performed. Results: The meta-analysis included 10 studies involving a total of 538 patients. The findings of the meta-analysis demonstrated that EBUS-TMC yielded an overall diagnostic rate of 89.59% (482/538), while EBUS-TBNA yielded a rate of 77.13% (415/538). The calculated inverse variance-weighted odds ratio was 2.63 (95% confidence interval, 1.86–3.72; p I2 value was 11%, indicating a statistically significant difference between the two techniques. The associated complications consisted of pneumothorax, pneumomediastinum, mediastinitis, and bleeding, with an incidence of 0.74% (4/538), 0.37% (2/538), 0.0% (0/538), and 1.12% (6/538), respectively. Moreover, the funnel plot displayed no discernible publication bias. Further subgroup analysis revealed a notable improvement in the diagnosis value for lymphoma (86.36% vs. 27.27%, p = 0.0006) and benign disorder (87.62% vs. 60.00%, p Conclusion: This review of the current available studies indicated that EBUS-TMC enhanced overall diagnostic yields compared to EBUS-TBNA, particularly for diagnosing benign disease and lymphoma. This procedure was not associated with any serious complications.

Inflammatory Myofibroblastic Tumour Presenting as Posterior Mediastinal Mass in a Child – A Rare Case Report

Posterior mediastinal tumours in children are difficult to diagnose due to non-specific clinical symptoms. Most of them are neurogenic in origin. However, large pulmonary neoplasms in children may also present as posterior mediastinal masses and may be misinterpreted as neurogenic tumour. We report a case of 6-year female child with recurrent vomiting who had inflammatory myofibroblastic tumour of the right lung which presented as posterior mediastinal mass on computed tomography.

Myocardial Infiltration in Primary Mediastinal B-Cell Lymphoma Detected by Cardiac Magnetic Resonance Imaging

Introduction: Cardiac involvement, particularly myocardial infiltration in primary mediastinal lymphoma, is a rare occurrence with an incidence of only 9% in known cases of primary malignancy. Neoplasm infiltration into the myocardium manifests through direct invasion, hematogenous spread, transvenous invasion through the great veins, or lymphangitic spreading in the mediastinal. Myocardial infiltration in lymphoma presents a grim prognosis and its treatment may be associated with specific risks, such as myocardial rupture. Various imaging modalities may detect cardiac involvement, with cardiac magnetic resonance (CMR) imaging considered the gold standard. CMR enables clear delineation of myocardial infiltration, making it valuable for local staging, pretreatment planning, and evaluating treatment response. Case Presentation: : A 37-year-old woman patient was diagnosed with primary mediastinal large B-cell lymphoma. Mild chest discomfort and shortness of breath were observed 3 months before hospital admission. A thorax CT scan showed a heterogeneous contrast-enhancing mass with a central necrotic area in the anterior mediastinum. Following thoracotomy and tumor debulking, the patient complained of severe crushing chest pain radiating to her back, accompanied by new T wave inversion on ECG and elevated cardiac troponin levels a week after surgery. Coronary angiogram results showed a normal coronary artery. Subsequent cardiac MRI showed tumor infiltration into the anterior pericardial space, as well as the myocardium of the left and right ventricles. Chemotherapy was promptly initiated, resulting in a gradual improvement of symptoms. Conclusions: In this study, we discuss the use of 3D-CRT in the re-irradiation of NPC with its limitation on obtaining optimum dose sculpture compared to more sophisticated and widely spread modalities like IMRT. However, with careful planning, we can still obtain optimum tumor dose, minimize OAR dose, and subsequently late toxicities that come after. We hope that this study can bring hope to centers with limited facilities, and we suggest further studies on reirradiation, especially in OAR dose tolerance guidelines.

Anterior mediastinal schwannoma: A rare case report

Mediastinal schwannomas are rare tumors that develop from peripheral nerve sheath in the mediastinum. Most commonly they are located in posterior mediastinum and are very unusual in anterior mediastinum like the present study of a 51 year old male. He presented with breathlessness, dyspnea and cough for 3 months. Radiological imaging, CT scan reports revealed a cystic SOL in anterior superior mediastinum. The patient underwent thoracotomy and on histopathological examination revealed features of schwannoma which was further confirmed by immunohistochemical study with S-100 protein. Prognosis is good for such tumours and no recurrence is yet reported.

Intrapulmonary schwannoma presenting as an asymptomatic lung mass: a case report

BackgroundSchwannomas are solitary well-circumscribed encapsulated benign tumors that exhibit Schwann cell differentiation, and arise directly from myelinated peripheral or central nerves. Although they are usually asymptomatic and found incidentally, schwannomas can cause symptoms due to compression of nearby structures which, depending on the location, can make clinical presentations widely variable. Despite their rarity, schwannomas have been documented in a number of locations including the limbs, cerebellopontine angle, posterior mediastinum, and, far more infrequently, the lungs.Case presentationIn this article, we report an incidental finding of an intrapulmonary schwannoma in a 59-year-old Pakistani woman who was grossly asymptomatic upon presentation to the cardiothoracic surgery clinic. An [18F]fluorodeoxyglucose positron emission tomography/computed tomography scan revealed a lobulated soft-tissue lesion measuring 23 mm × 23 mm in the lower lobe of the right lung. A computed tomography-guided core biopsy of the mass was performed, which revealed a benign spindle cell lesion based on histopathological examination and immunohistochemical staining. The mass was surgically resected via a right lower lobectomy, and subsequently confirmed to be an encapsulated neoplastic lesion composed of well-differentiated Schwann cells. There were no short- or long-term complications, morbidities, or recurrences based on 1-year follow-up.ConclusionThis report underscores the predominantly asymptomatic nature of schwannomas and reemphasizes the efficacy of surgical resection as a safe and curative procedure for a tumor of this nature. Albeit very rare, intrapulmonary schwannomas can be considered a differential diagnosis when encountering solitary asymptomatic pulmonary nodules or masses.

Solitary Neuroblastoma in the Scapula.

Majority of primary pediatric neuroblastomas occur in the abdomen, followed by posterior mediastinum. A 7-year-old girl presented worsening pain in the left shoulder, and a CT image of the chest revealed osseous destruction in the left scapula, suggestive of bone tumor. A biopsy was performed. Pathological result was consistent with neuroblastoma. A 123I scan with SPECT/CT images was performed, which showed only increased activity in the left scapula without any other foci of abnormal activity elsewhere.

Periesophageal Tuberculosis Abscess Post-Liver Transplantation Successfully Treated With Lumen-Apposing Metal Stent Cyst Esophagostomy

ABSTRACT The therapeutic utility of ultrasound-guided endoscopy has grown significantly in recent years. In this report, we describe a case of extrapulmonary tuberculosis in a liver transplant recipient found to have an encapsulated fluid collection in the inferior mediastinum, which was drained with an endoscopic ultrasound-guided technique, precluding the need for percutaneous or surgical intervention.

Strong opioids-induced cardiac, neurologic, and respiratory disorders: a real-world study from 2004 to 2023 based on FAERS.

Opioids are mainly used as adjuncts to the induction and maintenance of general anesthesia, postoperative analgesia, and treating moderate to severe cancer pain and chronic pain. However, the hazards of these drugs to various organ organs still need to be further explored. This study used the US FDA Adverse Event Reporting System (FAERS) database to determine whether commonly receiving opioids was higher than the baseline risk for all other medications. FAERS was asked about adverse events (AEs) for the opioids "morphine," "fentanyl," "oxycodone," "hydromorphone," "sufentanil," and "remifentanil" from the first quarter of 2004 (2004Q1) through the second quarter of 2023 (2023Q2). Disproportionality signaling analysis was performed by calculating reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM). AEs with system organ classes (SOCs) of "cardiac disease," "neurologic disease," and "respiratory, thoracic, and mediastinal disease" were then screened. The statistical analysis included 12,819,518 reports in the FAERS database from 2004Q1 to 2023Q2, of which 236,619 AEs were reported as "primary suspect" for the six drugs mentioned above, which were selected as "cardiac disorders," "nervous system disorders," and "respiratory, thoracic and mediastinal disorders." Some AEs identified in this study are consistent with the drug labeling, such as bradycardia, respiratory depression, and somnolence. In addition, some unexpected and significant acute adverse drug reactions (ADRs), such as toxic leukoencephalopathy and coma, may occur. This study identified potential new and unexpected ADRs for opioids, providing valuable evidence for safety studies of opioids.

A rare case of giant adrenal ganglioneuroma

Ganglioneuromas (GN) are rare benign tumors that typically occur in the posterior mediastinum or retroperitoneal region, but can also be found in adrenal glands. Up to 50% of patients are asymptomatic, but symptoms can arise from the mass effect or excessive secretion of catecholamines. Careful evaluation is necessary to differentiate GNs from other adrenal tumors. A 19-year-old female patient with no previous comorbidities was diagnosed with a right adrenal incidentaloma. Physical examination and routine laboratory tests were normal. Imaging revealed a solid lesion in the right adrenal gland, and excisional adrenalectomy was performed. Pathological examination confirmed the diagnosis of a right adrenal GN. The patient had an uneventful recovery and showed no recurrence during the follow-up period. Conclusion: After surgical removal of a benign neurogenic tumor, our patient had no tumor recurrence after five months, indicating a positive prognosis. However, long-term follow-up is still recommended because of reported cases of metastases and recurrence in some patients.

A Rare Case of High grade Epithelioid Malignant Neoplasm with CAM 5.2 Expression and (EML4–ALK) Fusion in a Pediatric Patient

Abstract Introduction/Objective ALK (anaplastic lymphoma kinase) fusions have been identified in lymphomas and diverse cancer types including carcinomas, melanomas and mesenchymal neoplasms such as inflammatory myofibroblastic tumors (IMT), epithelioid fibrous histiocytoma (EFH). Herein we present a (non IMT, non EFH) ALK rearranged aggressive epithelioid neoplasm. Methods/Case Report We report a 17-year-old male with a 14.0 cm mediastinal mass and extensive metastatic disease involving brain, bones, pleura and lymph nodes. The tumor was made of epithelioid like cell with round nuclei, prominent nucleoli and a moderate amount of cytoplasm, arranged in a nested pattern. Ki-67 showed a high proliferative index, >70%. The tumor cells were positive for CAM 5.2; weakly positive for AE1/3, ALK, CD30; focally positive for p63, p53, S100. Additional stains including CD117, PLAP, OCT-4, Sall-4, glypican-3, synaptophysin, chromogranin, CK5/6, p40, pan-melanoma, myogenin, CD99, WT1, CD34, CD45, CD138, MUM1, CD2, CD4, CD5, CD3, CD7, CD15, CD23, CD31, CD20, CD79a, CD15, PAX8, PAX5, CD43, MPO, desmin, D2-40, Calretinin, ERG, SOX-10, PD-L1 and NUT-1 were all negative. Both BRG and INI1 were retained. The keratin positivity and the lack of “hallmark” cells made anaplastic large cell lymphoma (ALCL) less likely. The absence of desmin and CD30 excluded the rare epithelioid IMT sarcoma. Next-generation sequencing detected an (EML4–ALK) fusion. A diagnosis of high- grade epithelioid malignant neoplasm with (EML4–ALK) fusion was made. Most cases of this category were described as low grade-appearing spindled cells within a myxoid stroma arranged in fascicles (+S100, +CD34) and have unaggressive behavior. Only three cases, were characterized by epithelioid high- grade morphology and metastatic nature. They shared features like little collagenous stroma, conspicuous mitotic activity and tumor necrosis. Results (if a Case Study enter NA) NA Conclusion Identification of kinase fusions was essential for precise classification, better knowledge of this epithelioid high grade malignant neoplasm and for targeted therapy purposes. The significant clinicopathologic heterogeneity of this emerging group requires further investigation.

Thymoma Involved by Small Lymphocytic Lymphoma (SLL): A Rare and Challenging Diagnosis

Abstract Introduction/Objective Thymoma is a malignant neoplasm arising from the epithelial cells of the thymus. It usually affects patients between the fourth and sixth decades of life. There is a strong association of thymoma with myasthenia gravis and other paraneoplastic syndromes Thymic epithelial tumors are the most common tumors of the anterior mediastinum; however, lymphomas frequently present as mediastinal masses. Concurrent thymoma and lymphoma affecting the thymus is very rare. Methods/Case Report A 79-year-old woman with a history of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) presented with night sweats and weight loss. Chest CT revealed small pulmonary nodules, a 3.3 x cm anterior mediastinal mass and enlarged hilar lymph nodes. Fine needle aspiration (FNA) of the mass revealed a mixture of lymphocytes and epithelial cells. Flow cytometry showed a monoclonal B-cell population, and double CD4/CD8-positive T-cells consistent with thymocytes. Core biopsy showed scattered neoplastic epithelial cells interspersed among densely packed small lymphocytes. Scattered and small clusters of epithelial cells were highlighted by the CK AE1/3 immunostain. CD3 and PAX5 showed the thymocytes and infiltrating B-cells, respectively. Based on cytomorphologic, flow cytometric, histopathologic, and immunohistochemical findings, the diagnosis of thymoma, type B2 involved by SLL was rendered. Results (if a Case Study enter NA) N/A Conclusion A multimodality diagnostic work-up integrating cytomorphology, flow cytometry and immunohistochemistry allowed recognizing this unusual association.

Cooperative Somatic Alterations in XPO1 and TNFAIP3 (A20) Promote Immune Modulation and Tissue Infiltration in Primary Mediastinal B Cell Lymphoma

Background: Primary Mediastinal B cell lymphoma (PMBCL) is an aggressive large B cell non-Hodgkin lymphoma typically presenting as a mass in the anterior mediastinum in early adulthood, disproportionately affecting females (2:1). Previous studies have identified constitutive activation of the NF-κB pathway and immune evasion as hallmark features of PMBCL. The master negative regulator of canonical NF-κB, TNFAIP3 (A20), is inactivated in ~25-60% of PMBCL cases via disruptive mutations or deletions. Gains of the 2p16.1-15 locus ( REL, XPO1, BCL11A) are seen in ~40-75% of PMBCL cases. Interestingly, PMBCL cases with 2p16.1-15 gain/amplification display concomitant increases in XPO1 expression but lack correlative increases in REL or BCL11A. In addition, XPO1 mutations are seen in ~15-33% of PMBCL cases, with the most prevalent mutation (E571K) implicated in NF-KB activation. Despite the established occurrence of genetic events impacting XPO1 and A20 in PMBCL, the cooperative potential of these alterations remains unexplored. Consequently, we conducted an extensive review of literature describing the PMBCL genomic landscape and utilized in vivo models to examine the combined potential of XPO1 and A20 alterations to promote lymphomagenesis. Methods: Genomic data was obtained from NGS analyses from a total of 233 PMBCL patients across 6 independent published research studies and analyzed for cooccurrence of A20 & XPO1 alterations (Camus et al. 2022; Chapuy et al. 2019; Lacy et al. 2020; Mareschal et al. 2015; Mottock et al. 2019; Tuveri et al 2022). For in vivo analysis, we developed a murine model of B cell specific overexpression of wildtype (WT) or E571K- XPO1 with CD19.cre driven depletion of A20 (Eµ-XPO1xA20 KO). Whole body histopathologic evaluation of FFPE tissue with H&E staining was performed on 6-month-old, age and sex matched littermate mice. Results: We found co-occurrence of inactivating events in A20 and XPO1 missense mutations impacting 15% of PMBCL evaluated cases, with consistent results seen across all studies (range: 13.8-20%). As expected, A20 mutations/del were more prevalent than XPO1 mutations across all studies (OR 2.46, 95% CI 0.84-7.18, p = 0.02). XPO1 mutated cases trended towards a greater likelihood of having co-occurring A20 mutations (OR 8.51, 95% CI 0.84-86.47, p = 0.08). XPO1 mutations and gain (2p16) were found to be mutually exclusive events with gains co-occurring with A20 mutations/del in ~17% of PMBCL cases evaluated. Analysis of survival of PMBCL patients with cooccurring A20 inactivating alterations and XPO1 mutations is ongoing although preliminarily trend towards reduced mean 2-year survival (p=0.056) compared to all others are observed. Taken together, co-occurring genetic alterations effecting A20 and XPO1 are prevalent in PMBCL the alternative biology stemming from potential cooperative mechanisms may represent an aggressive subgroup of PMBCL. To evaluate concurrent B cell-specific alterations of A20 and XPO1 in vivo we utilized Eµ-XPO1xA20 KO mouse models. Performing histopathology in 6-month-old mice we observed enlarged lymph nodes due to marked increases in lymphocytes within the cortex, paracortex, medulla, and sinuses in mice with loss of functional A20, particularly in Eµ-XPO1xA20 KO mice with overexpression of WT XPO1. Increased lymphocyte populations drove overall enlargement of the node (mandibular, mesenteric, pancreatic, and mediastinal) and distorted normal architecture, featuring small lymphocytes populating sinus regions and larger lymphocytes populating areas resembling follicles. Eµ-XPO1(WT & E571K)xA20 KO mice additionally featured mild mononuclear infiltrates in the lung and salivary glands; all of which were observed with increased severity compared to A20KO, Eµ-XPO1, or non-transgenic littermates. Significance: We identified co-occurring genetic lesions impacting A20 and XPO1 in PMBCL tumors and show that these alterations synergize in vivo leading to nodal/extranodal lymphocyte infiltration. The immunomodulatory effects appear to be driven by the cooperation of XPO1 overexpression, more so than mutation, and A20 inactivation in young mice. Further investigation of these models will allow elucidation of underlying cooperative mechanisms and reveal targetable pathways in PMBCL.

Patterns of Care and Outcome in Adolescent and Young Adults (AYA) Lymphomas- a Multicenter HCC (Hematologic Cancer Consortium) Registry Study from India

Introduction There are no recommendations pertaining to lymphoma in AYA population. It represents a paramount opportunity for fostering collaborative research among pediatric and medical oncologists. Prior to embarking on any collaborative interventional research, comprehensive demographic data, patterns of care, and outcomes related to AYA lymphomas are imperative. Hence, the HCC registry database can be utilized to do this analysis of all AYA lymphoma in India which will set the benchmark for future research in this area. Methods This was a retrospective study including data from participating member centers of the HCC registry. Data was collected using an online data capture program, which is already in place as part of the HCC registry and has been in use for the past 5 years. Each center maintains its source documents and is responsible for data accuracy. All patients diagnosed with lymphoma between January 01, 2020, and June 31, 2022, were included in the study. The treatment patterns for AYA lymphomas vary from intensive protocols like in the pediatric age group to less intense protocols used in adults. This registry data captured this heterogeneity in treatment patterns and outcomes. The primary endpoint of the study was event-free survival (EFS) which was defined as the time from the first cycle of chemotherapy to progression, relapse, second malignancy, or death. The secondary outcomes were response rates and overall survival. Results The data was collected from eight participating centers of India out of which five are public sector hospitals and three are trust-based private hospitals. A total of 677 AYA lymphomas were registered between January 01, 2020, and June 31, 2022. Treatment was given to 582 patients and the follow-up data was available for 570 patients. The median age of the cohort was 23 years (IQR-19, 27) with 65% of them being males. Almost 50 % of patients had Hodgkin lymphoma and the rest were non-Hodgkin lymphoma (NHL) as depicted in Figure 1. Among NHLs; DLBCL, T-LBL, PMBCL, ALCL, and Burkitt lymphoma were seen in 113(17%), 39(6%), 36(5%),28(4%), and 19(3%) respectively. PETCT was done in 70% patients at baseline. Early-stage disease was seen in 233 patients (35%), advanced stage in 366 patients (56%), and 60 patients (9%) were not staged at baseline. Bulky mediastinum was seen in 1/4 th of the patients out of which the majority (85%) were Hodgkin lymphoma and PMBCL. Extra nodal site involvement was seen in 43% of patients out of which marrow involvement constituted almost half. Out of 677 patients, 582 patients (86%) received treatment at their respective centers and only 5 % of patients could not receive any treatment due to financial constraints. Among 298 treated cases of Hodgkin lymphoma, 245(82 %) patients received ABVD while escBEACOPP was given to 28(9%) patients. In DLBCL, out of 87 patients, 59(68%) received CHOP-R, 10(11%) received DA-REPOCH, 8(9%) received GMALL NHL protocol and the rest 10(11%) received other intensive regimens. Around one-third(36%) patients received radiation therapy out of which 90 patients (57%) received it as part of definitive treatment and 50 (31%) patients received it as consolidation to residual site. The median follow-up of the entire cohort was 13 months(IQR-8, 12). Out of 570 patients where follow-up was available, the overall EFS was 76. % ± 2.4%. The EFS outcome according to the histopathological subtype is depicted in Figure 2. Relapse or progression occurred in 72 patients (12.5%) out of which 50(72%) could receive any form of salvage therapy including transplant. The most common cause of death was progressive disease in 18 patients (50%) and death due to toxicity in 3(8%), and unknown causes in 16(40%) patients. The presence of bulky disease or bulky mediastinum did not have an impact on EFS outcome.There was no difference in EFS between DLBCL or High-grade B- NHL NOS. Conclusion This is the one of largest real-world data on AYA lymphoma. The majority were Hodgkin lymphoma followed by DLBCL. Most patients received adult-type regimens or Hodgkin as well as non-Hodgkin lymphoma. The use of radiation was high (1/3 rd) which could be due to a higher burden of bulky and mediastinal disease in our cohort. The EFS outcomes are comparable to the published literature. This data will set the benchmark for future collaborative studies in India and abroad for AYA lymphoma.

Nelarabine (NEL), Pegylated Asparginase (PEG) and Venetoclax (VEN) Incorporated to HCVAD Chemotherapy in the Frontline Treatment of Adult Patients with T-Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma (T-ALL/T-LBL)

Background: The incorporation of novel agents such as NEL and PEG to frontline therapy has been associated with improved outcomes in pediatric patients (pts) with T-ALL/LBL, but has not been extensively studied in the adult pts. BCL-2 upregulation has been demonstrated in T-lymphoblasts, especially of the early T-cell precursor (ETP) ALL and addition of VEN (BCL-2 inhibitor) may be beneficial. Methods: Pts with previously untreated or minimally pre-treated T-ALL/LBL were eligible if they had an ECOG PS ≤3, creatinine ≤ 2 mg/dL, total bilirubin ≤ 2 mg/dL and ALT/AST ≤ 4 x ULN. Pts received 8 cycles (C) of HCVAD (C 1,3, 5, 7) alternating with high dose Ara-C and methotrexate (MTX) (C 2, 4, 6, 8) at approximately 3-week intervals. Two cycles of NEL (650 mg/m 2 daily x 5) were initially administered after C8 (cohort 1). Later, after a protocol amendment, they were administered after C4 and C5 (cohort 2). Subsequently, the protocol was amended to add PEG (1500 IU/m 2 capped at 3750 IU; for pts age 60 or older, dose was 1000 IU/m 2, capped at 2000 IU) on day 5 of the NEL cycles (cohort 3) and more recently, VEN 400 mg daily was added on the first 7 days of each of 8 cycles of therapy (cohort 4); this was later modified to be given for 7 days during the induction cycle to all pts and reduced to 3 days per post-induction cycle only in pts with ETP-ALL or those with persistent measurable residual disease (MRD) and all other pts did not receive VEN after C1 (cohort 5). Pts with ETP-ALL were referred for allogeneic stem cell transplant (allo-SCT) in first complete remission (CR). After the completion of the intensive phase; pts in all cohorts received 30 cycles of maintenance therapy with monthly POMP (prednisone, vincristine, MTX, prednisone) and early intensification with NEL/PEG on C6 and 7 and late intensification with MTX/PEG in C18 and HCVAD on C19. All pts received 8 intrathecal chemotherapy with MTX alternating with Ara-C and mediastinal radiation was considered in pts with bulky mediastinal disease. Results: Between 7/2007 and 12/2022, 133 pts were enrolled in the 5 study cohorts sequentially (cohort 1= 30, 2= 49, 3=17, 4=16, 5=21) (Table 1). Eighty pts (60%) had T-ALL, 52 T-LBL (39%) and 1 pt had ETP/myeloid bi-phenotypic leukemia. The median age for the entire cohort was 35 years (yrs) (range 18-78), 102 pts were male (77%), 83 pts (62%) were white and 18 pts (14%) had PS ≥2. Overall, 24 pts (18%) had an ETP phenotype and another 19 pts (14%) had a near-ETP phenotype. Six pts (5%) had central nervous system disease at diagnosis, 72 pts (54%) had mediastinal disease, 49 of 80 (61%) T-ALL pts had extramedullary disease and 20 pts (15%) were in complete remission (CR) at trial enrollment after minimal pre-enrollment therapy. Overall response (CR+CRp+CRi+PR) on trial was attained in 109/113 (95%) pts [CR= 101 (89%), CRi/CRp= 3 (3%), PR=5 (4%)]. CR/CRi/CRp was attained in 36/41 (88%) pts with ETP/near-ETP ALL and 60/64 (94%) of confirmed near-ETP ALL pts ( p=0.31). At a median follow-up of 62 months (mos), the median overall survival (OS) was not reached (NR), 3-yr OS was 71% and 5-yr OS was 64% . The 3-yr OS for pts treated with HCVAD+NEL (cohort 1+2), HCVAD+NEL+PEG (Cohort 3) and HCVAD+NEL+PEG+VEN (Cohort 4+5) were 66%, 88% and 76% respectively (Figure 1). Median OS was not reached for both VEN cohorts, while 3-yr OS was 72% in cohort 4 compared to 88% in cohort 5 ( p=0.51), with significantly shorter follow-up for the latter (33 mos vs. 15 mos). Amongst the 124 pts who had CR/CRp/CRi, the median RFS was NR and 5-yr RFS was 68%. 24 (18%) pts underwent SCT in first remission, including 20 (83%) with ETP or near-ETP ALL. The median OS was shorter in the 44 ETP/near-ETP pts compared to the 77 pts with non-ETP phenotype (71 mos vs. NR, p=0.08). 30 and 60-day mortality was 0% and 1%. 10 pts (7.5%) died in remission (3, 5 and 2 pts in cohorts 1, 2 and 4 respectively) including 1 after SCT, 4 after developing therapy-related acute myeloid leukemia and 5 from infectious complications. Conclusion: The ongoing phase 2 trial of NEL, ASP, VEN added to the HCVAD regimen shows promising long-term survival in adult pts with T-ALL/LBL with 3-yr OS of 76%-88% in pts treated with HCVAD+NEL+PEG +/- VEN. Larger prospective trials and longer follow-up are needed to demonstrate further benefit.

Mutational Landscape of Diffuse Large B-Cell Lymphoma (DLBCL) in Mexican Patients

Background. Diffuse Large B Cell Lymphoma (DLBCL) is the most common B-cell malignancy (1), recently classified with genomic sequencing and exome analysis into clusters with clinical implications (2,3). However, this analysis has not been informed neither in Mexican, or Latin-American population. The aim of this study was to describe the mutational landscape and its correlation with the clinical outcome in Mexican patients with DLBCL. Material and methods. A prospective, observational study of patients with diagnosis of DLBCL, attended at the National Cancer Institute in Mexico City. Inclusion criteria: patients > 18 years, diagnosis of DLBCL, without previous treatment and candidate to be treated with RCHOP. IRB approval was: Register number CEI/966/15. All signed informed consent. Clinical & pathological variables were analyzed. All patients were treated with 6 cycles of RCHOP. Clinical response was evaluated by PET-CT. Samples: DNA was extracted from paraffin-embedded tissue of the primary neoplasm using the kit Quick-DNA/RNA FFPE kit (Zymo Research). A custom panel (6,026 oligos) was used for the sequencing of coding regions and splicing sites of 79 genes associated with lymphomas. Therafter, the bioinformatic analysiswas carried out using Ion Torrent Suite Browser version 5.0 and Ion Reporter version 5.18. Variant calling was performed with Torrent Variant Caller. The following databases were used: Cancer Genome Interprteter (CGI), ClinVar (201706), COSMIC (v86), PolyPhen (v2.2.2), SIFT (v5.2.2), FATHMM (v2.1), gnomAD (r2.0.1), and the Variant Effect Predictor (v93.2). All variants had a depth greater than 500X. Statistical analysis. Descriptive statistics for clinical variables. Associations between clinical and pathological characteristics were assessed with the frequency of SNVs and InDels. Survival curves were estimated using the Kaplan-Meier method. The association of the overall survival (OS) and the recurrence-free survival (RFS) was evaluated with Log-Rank test. Statistical significance was set at p-value < 0.05. Cox proportional-hazard regression analysis was used to identify the variables predicting overall survival (OS). All statistical analyses were performed using R software (v4.2.2) (https://cran.r-project.org, accessed on 23rd May 2023) and SPSS version 25 software (IBM, Corp., Armonk, NY). Results We included 185 patients, median + SD age 59.3 + 14.1 years. Most (n=128, 69.2 %) were in ECOG score < 2, without B symptoms (n=131, 70.8 %), in advanced disease (n=134, 72.4%), and were germinal-center (GC) (n=126, 68.1 %), and 26 (14.1 %) were double hit lymphomas. At least a driver mutation was found in 110 cases (59.4 %). The genes with driver mutations most frequently were: TP53, EZH2, CREBBP, NOTCH1 and KMT2D. ( figure 1). The EZH2 mutations and KMT2D mutations were more frequent in female: ( EZH2 mutated [n=22/34, 64.7%], p=0.047]) ( KMT2D mutated, 75%, p=0.034), and had a higher frequency of bulky disease (63.3 %, p= 0.05). In contrast, MYD88 mutations were more frequent in male (MYD88 mutations: 76.9 %], p= 0.042). Response to R-CHOP treatment was: Complete (n= 129 (69.7%), partial (n=10, 5.4 %), or stable disease (n=3, 1.6 %); 26 patients (14 %) progressed during treatment. Median follow-up + SD was 41.99 + 21.4 months. The RFS was 60 % to 80 months and OS was 70 % to 84 months. ECOG >2 (p=0.002 [95 %CI: 1.52-3.97]), mutations at genes EZH2 (p=0.007 [95% CI: 0.193 -0.0.58), CREBBP (p=0.004 [95 % CI: 1.59 - 11.85]), and ARID1A (p= 0.027 [95 % CI: 1.34 - 131.45] were factors influencing on OS by univariate analysis. The multivariate analysis confirmed that an ECOG >2 (p=0.001 [95 CI: 1.46-3.34]) had a negative impact on OS. In contrast, EZH2 mutations (p=0.025 [95 % CI: 0.12 -0.86]) were a protective factor. Conclusions: This is the first approach to describe the genomic landscape in Latino-american population. The presence of EZH2 and KMT2 mutations were more frequent in female patients with mediastinal and bulky disease. After multivariate analysis, only the presence of EZH2 mutations was the only genomic factor influencing on OS. These results require to be confirmed by further studies.