238 results on '"Chauhan, Aman"'
Search Results
202. AJCC Cancer Staging System Version 9: Practice-Informing Updates for Gastroenteropancreatic Neuroendocrine Tumors.
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Chan K, Chauhan A, and Shi C
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- Humans, Practice Guidelines as Topic standards, Prognosis, Neuroendocrine Tumors pathology, Pancreatic Neoplasms pathology, Pancreatic Neoplasms surgery, Neoplasm Staging, Stomach Neoplasms pathology, Stomach Neoplasms surgery, Intestinal Neoplasms pathology
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- 2024
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203. Inhibition of ribonucleotide reductase subunit M2 enhances the radiosensitivity of metastatic pancreatic neuroendocrine tumor.
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Chow Z, Johnson J, Chauhan A, Jeong JC, Castle JT, Izumi T, Weiss H, Townsend CM Jr, Schrader J, Anthony L, Yang ES, Evers BM, and Rychahou P
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- Humans, Animals, Cell Line, Tumor, Phosphorylation, Neuroendocrine Tumors pathology, Neuroendocrine Tumors genetics, Neuroendocrine Tumors radiotherapy, Neuroendocrine Tumors drug therapy, Neuroendocrine Tumors enzymology, Neuroendocrine Tumors metabolism, Lung Neoplasms secondary, Lung Neoplasms radiotherapy, Lung Neoplasms pathology, Lung Neoplasms genetics, Ataxia Telangiectasia Mutated Proteins antagonists & inhibitors, Ataxia Telangiectasia Mutated Proteins metabolism, Ataxia Telangiectasia Mutated Proteins genetics, Tumor Suppressor Proteins genetics, Tumor Suppressor Proteins metabolism, Signal Transduction drug effects, Checkpoint Kinase 1 antagonists & inhibitors, Checkpoint Kinase 1 metabolism, Checkpoint Kinase 1 genetics, Mice, Checkpoint Kinase 2 metabolism, Checkpoint Kinase 2 genetics, Checkpoint Kinase 2 antagonists & inhibitors, Female, RNA Interference, DNA-Activated Protein Kinase, Pancreatic Neoplasms pathology, Pancreatic Neoplasms radiotherapy, Pancreatic Neoplasms genetics, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms enzymology, Ribonucleoside Diphosphate Reductase genetics, Ribonucleoside Diphosphate Reductase antagonists & inhibitors, Ribonucleoside Diphosphate Reductase metabolism, Radiation-Sensitizing Agents pharmacology, Apoptosis drug effects, Cell Proliferation drug effects, Xenograft Model Antitumor Assays, Radiation Tolerance drug effects, Mice, Nude
- Abstract
Ribonucleotide Reductase (RNR) is a rate-limiting enzyme in the production of deoxyribonucleoside triphosphates (dNTPs), which are essential substrates for DNA repair after radiation damage. We explored the radiosensitization property of RNR and investigated a selective RRM2 inhibitor, 3-AP, as a radiosensitizer in the treatment of metastatic pNETs. We investigated the role of RNR subunit, RRM2, in pancreatic neuroendocrine (pNET) cells and responses to radiation in vitro. We also evaluated the selective RRM2 subunit inhibitor, 3-AP, as a radiosensitizer to treat pNET metastases in vivo. Knockdown of RNR subunits demonstrated that RRM1 and RRM2 subunits, but not p53R3, play significant roles in cell proliferation. RRM2 inhibition activated DDR pathways through phosphorylation of ATM and DNA-PK protein kinases but not ATR. RRM2 inhibition also induced Chk1 and Chk2 phosphorylation, resulting in G1/S phase cell cycle arrest. RRM2 inhibition sensitized pNET cells to radiotherapy and induced apoptosis in vitro. In vivo, we utilized pNET subcutaneous and lung metastasis models to examine the rationale for RNR-targeted therapy and 3-AP as a radiosensitizer in treating pNETs. Combination treatment significantly increased apoptosis of BON (human pNET) xenografts and significantly reduced the burden of lung metastases. Together, our results demonstrate that selective RRM2 inhibition induced radiosensitivity of metastatic pNETs both in vitro and in vivo. Therefore, treatment with the selective RRM2 inhibitor, 3-AP, is a promising radiosensitizer in the therapeutic armamentarium for metastatic pNETs., Competing Interests: Declaration of Competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.) more...
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- 2024
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204. Critical updates in neuroendocrine tumors: Version 9 American Joint Committee on Cancer staging system for gastroenteropancreatic neuroendocrine tumors.
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Chauhan A, Chan K, Halfdanarson TR, Bellizzi AM, Rindi G, O'Toole D, Ge PS, Jain D, Dasari A, Anaya DA, Bergsland E, Mittra E, Wei AC, Hope TA, Kendi AT, Thomas SM, Flem S, Brierley J, Asare EA, Washington K, and Shi C more...
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- Humans, United States, Neuroendocrine Tumors pathology, Neuroendocrine Tumors diagnosis, Neuroendocrine Tumors therapy, Neoplasm Staging methods, Pancreatic Neoplasms pathology, Pancreatic Neoplasms diagnosis, Stomach Neoplasms pathology, Stomach Neoplasms diagnosis, Intestinal Neoplasms pathology, Intestinal Neoplasms diagnosis, Intestinal Neoplasms therapy
- Abstract
The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including gastroenteropancreatic neuroendocrine tumors (GEP-NETs), is meant to be dynamic, requiring periodic updates to optimize AJCC staging definitions. This entails the collaboration of experts charged with evaluating new evidence that supports changes to each staging system. GEP-NETs are the second most prevalent neoplasm of gastrointestinal origin after colorectal cancer. Since publication of the AJCC eighth edition, the World Health Organization has updated the classification and separates grade 3 GEP-NETs from poorly differentiated neuroendocrine carcinoma. In addition, because of major advancements in diagnostic and therapeutic technologies for GEP-NETs, AJCC version 9 advocates against the use of serum chromogranin A for the diagnosis and monitoring of GEP-NETs. Furthermore, AJCC version 9 recognizes the increasing role of endoscopy and endoscopic resection in the diagnosis and management of NETs, particularly in the stomach, duodenum, and colorectum. Finally, T1NXM0 has been added to stage I in these disease sites as well as in the appendix., (© 2024 The Authors. CA: A Cancer Journal for Clinicians published by Wiley Periodicals LLC on behalf of American Cancer Society.) more...
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- 2024
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205. Leveraging Programmatic Collaboration for a Radiopharmaceutical Clinic.
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Kunos CA, Martin ME, Georgiou MF, Kuker RA, and Chauhan A
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Radiation oncologists, radiopharmacists, nuclear medicine physicians, and medical oncologists have seen a renewed clinical interest in radiopharmaceuticals for the curative or the palliative treatment of cancer. To allow for the discovery and the clinical advancement of targeted radiopharmaceuticals, these stakeholders have reformed their trial efforts and remodeled their facilities to accommodate the obligations of a program centered upon radioactive investigational drug products. Now considered informally as drugs and not beam radiotherapy, radiopharmaceuticals can be more easily studied in the traditional clinical trial enterprise ranging from phase 0-I to phase III studies. Resources and physical facilities allocated to radiopharmaceuticals have brought forth new logistics and patient experience for safe and satisfactory drug delivery. The clinical use of theranostic agents-that is, diagnostic and therapeutic radionuclide pairs-has accelerated radiopharmaceutical development. more...
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- 2024
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206. Exosomal Dynamics and Brain Redox Imbalance: Implications in Alzheimer's Disease Pathology and Diagnosis.
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Bir A, Ghosh A, Chauhan A, Saha S, Saini AK, Bisaglia M, and Chakrabarti S
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Oxidative burden plays a central role in Alzheimer's disease (AD) pathology, fostering protein aggregation, inflammation, mitochondrial impairment, and cellular dysfunction that collectively lead to neuronal injury. The role of exosomes in propagating the pathology of neurodegenerative diseases including AD is now well established. However, recent studies have also shown that exosomes are crucial responders to oxidative stress in different tissues. Thus, this offers new insights and mechanistic links within the complex pathogenesis of AD through the involvement of oxidative stress and exosomes. Several studies have indicated that exosomes, acting as intracellular communicators, disseminate oxidatively modified contents from one cell to another, propagating the pathology of AD. Another emerging aspect is the exosome-mediated inhibition of ferroptosis in multiple tissues under different conditions which may have a role in neurodegenerative diseases as well. Apart from their involvement in the pathogenesis of AD, exosomes enter the bloodstream serving as novel noninvasive biomarkers for AD; some of the exosome contents also reflect the cerebral oxidative stress in this disease condition. This review highlights the intricate interplay between oxidative stress and exosome dynamics and underscores the potential of exosomes as a novel tool in AD diagnosis. more...
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- 2024
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207. Development and validation of a chromatin regulator signature for predicting prognosis hepatocellular carcinoma patient.
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Mao J, Song F, Zhang Y, Li Y, Inchingolo R, Chauhan A, Midorikawa Y, Chen Z, and Tang W
- Abstract
Background: Hepatocellular carcinoma (HCC) is a malignancy with a bleak prognosis. Although emerging research increasingly supports the involvement of chromatin regulators (CRs) in cancer development, CRs in HCC patients have not received proportionate attention. This study aimed to investigate the role and prognostic significance of CRs in HCC patients, providing new insights for clinical diagnosis and treatment strategies., Methods: We analyzed 424 samples in The Cancer Genome Atlas-Liver hepatocellular carcinoma (TCGA-LIHC) data to identify key CR genes associated with HCC prognosis by differential expression and univariate Cox regression analyses. LASSO-multivariate Cox regression method was used for construction of a prognostic signature and development of a CR-related prognosis model. The prognosis capacity of the model was evaluated via Kaplan-Meier method. Relationship between the model and tumor microenvironment (TME) was evaluated. Additionally, clinical variables and the model were incorporated to create a nomogram. The role of the prognostic gene MRG-binding protein ( MRGBP ) in HCC was elucidated by immunohistochemistry and semiquantitative analysis., Results: A risk score model, comprising B-lymphoma Mo-MLV insertion region 1 ( BMI1 ), chromobox 2 ( CBX2 ), and MRGBP , was constructed. The area under the curve (AUC) of the CR-based signature is 0.698 (P<0.05), exhibiting robust predictive power. Functional and pathway analyses illuminated the biological relevance of these genes. Immune microenvironment analysis suggested potential implications for immunotherapy. Drug sensitivity analysis identified agents for targeted treatment. Clinical samples show that MRGBP is highly expressed in HCC tissues., Conclusions: This CR-based signature shows promise as a valuable prognostic tool for HCC patients. It demonstrates predictive capabilities, independence from other clinical factors, and potential clinical applicability. In addition, we need more experiments to validate our findings. These findings offer insights into HCC prognosis and treatment, with implications for personalized medicine and improved patient outcomes., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-23-996/coif). R.I. receives payment or honoraria for lectures from Cook and Boston Scientific, outside the submitted work. The other authors have no conflicts of interest to declare., (2024 Journal of Gastrointestinal Oncology. All rights reserved.) more...
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- 2024
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208. A feasibility (pilot) mixed methods study of an innovative non-pharmacological breath-based yoga and social-emotional intervention program in an at-risk youth sample in London, Canada.
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Vasudev A, Ionson E, Sathiaselan J, Thatipalli A, Chauhan A, Hassan C, Sukhera J, Speechley M, and Forchuk C
- Abstract
Background: Various service provision models for youth at risk of homelessness have been researched and implemented, including access to housing and physical and mental health resources. However, even with these interventions, we remain unaware of how best to manage symptoms of depression and anxiety and the rate of drug use in these populations primarily because of a lack of feasibility data., Methods: This paper presents the results of a mixed-methods study in London, Canada, that examined the feasibility of implementing a biopsychosocial intervention, SKY Schools, in at-risk youth aged between 16 and 25 (n = 49). The study also recorded qualitative responses about the program's usefulness from the perspective of the service users. The SKY Schools intervention consisted of social-emotional learning combined with Sudarshan Kriya Yoga, a standardized yoga-based breathing exercise routine. The intervention program was divided into two phases: an active learning phase and a reinforcement phase. The following feasibility outcome measures were collected: (1) the number of potential participants approached per month, (2) number (proportion) who were successfully screened, (3) the proportion of screened participants who enrolled, (4) the rate of retention in the study, (5) rate of adherence to study protocol, (6) proportion of planned ratings that were completed, (7) intervention cost per case, (8) completeness of final data for analysis, (9) length of time to collect all data, (10) quality of all collected data, (11) determining if partnering community organizations were willing to conduct the study as per study protocol, (12) determining if there were any capacity issues with partners providing intervention and investigators being able to perform the tasks that they were committed to doing, (13) determining if there were any problems of entering the data into a computer, (14) preliminary data about the safety of the intervention, and (15) preliminary estimate of treatment effects., Results: All feasibility outcome measures were collectible. In the city of London, Canada it was feasible to conduct a pilot study in this population of youth at risk of homelessness. Foremost among the findings was a high retention rate (61.2%) and overall positive qualitative feedback with a number of potential suggestions to improve the delivery and quality of the intervention. However, we had a significantly low recruitment rate (0.27 participants per week) suggesting that multiple sites will be needed to achieve an adequate sample size for a subsequent definitive trial., Conclusions: Future researchers may consider the findings of this feasibility study when designing a randomized control trial to further assess the efficacy and tolerability of SKY Schools., Trial Registration: Trial registration: Clinicaltrials.gov, identifier NCT02749240. Registered April 22, 2016, https://clinicaltrials.gov/ct2/show/NCT02749240 ., (© 2024. The Author(s).) more...
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- 2024
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209. Role of CDK4/6 inhibitors in targeting Rb proficient small cell lung cancer.
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Corbett V, Sen T, and Chauhan A
- Abstract
Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-23-337/coif). V.C. declares that she formerly owned equity in Pfizer, BristolMyers Squibb, Seagen, and Viatris. She is the recipient of a K12 award for a project unrelated to this manuscript. A.C. serves as consultant for Novartis, Curium, Tersera, Ipsen, and Seneca Therapeutics. A.C. has received research support from BMS, Clovis, Nanopharmaceutics, EMD Serono, Allarity, and Seneca Therapeutics, and CARIS. A.C. is co-chair of the NANETS communications committee, and a member of AJCC NETs panel, ASCO NETs Guidelines committee and NCI’s NET Task Force. The other author has no conflicts of interest to declare. more...
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- 2024
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210. Berzosertib Plus Topotecan vs Topotecan Alone in Patients With Relapsed Small Cell Lung Cancer: A Randomized Clinical Trial.
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Takahashi N, Hao Z, Villaruz LC, Zhang J, Ruiz J, Petty WJ, Mamdani H, Riess JW, Nieva J, Pachecho JM, Fuld AD, Shum E, Chauhan A, Nichols S, Shimellis H, McGlone J, Sciuto L, Pinkiert D, Graham C, Shelat M, Kattappuram R, Abel M, Schroeder B, Upadhyay D, Krishnamurthy M, Sharma AK, Kumar R, Malin J, Schultz CW, Goyal S, Redon CE, Pommier Y, Aladjem MI, Gore SD, Steinberg SM, Vilimas R, Desai P, and Thomas A more...
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- Humans, Male, Middle Aged, Female, Topotecan adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Recurrence, Small Cell Lung Carcinoma pathology, Lung Neoplasms pathology
- Abstract
Importance: Patients with relapsed small cell lung cancer (SCLC), a high replication stress tumor, have poor prognoses and few therapeutic options. A phase 2 study showed antitumor activity with the addition of the ataxia telangiectasia and Rad3-related kinase inhibitor berzosertib to topotecan., Objective: To investigate whether the addition of berzosertib to topotecan improves clinical outcomes for patients with relapsed SCLC., Design, Setting, and Participants: Between December 1, 2019, and December 31, 2022, this open-label phase 2 randomized clinical trial recruited 60 patients with SCLC and relapse after 1 or more prior therapies from 16 US cancer centers. Patients previously treated with topotecan were not eligible., Interventions: Eligible patients were randomly assigned to receive topotecan alone (group 1), 1.25 mg/m2 intravenously on days 1 through 5, or with berzosertib (group 2), 210 mg/m2 intravenously on days 2 and 5, in 21-day cycles. Randomization was stratified by tumor sensitivity to first-line platinum-based chemotherapy., Main Outcomes and Measures: The primary end point was progression-free survival (PFS) in the intention-to-treat population. Secondary end points included overall survival (OS) in the overall population and among patients with platinum-sensitive or platinum-resistant tumors. The PFS and OS for each treatment group were estimated using the Kaplan-Meier method. The log-rank test was used to compare PFS and OS between the 2 groups, and Cox proportional hazards models were used to estimate the treatment hazard ratios (HRs) and the corresponding 2-sided 95% CI., Results: Of 60 patients (median [range] age, 59 [34-79] years; 33 [55%] male) included in this study, 20 were randomly assigned to receive topotecan alone and 40 to receive a combination of topotecan with berzosertib. After a median (IQR) follow-up of 21.3 (18.1-28.3) months, there was no difference in PFS between the 2 groups (median, 3.0 [95% CI, 1.2-5.1] months for group 1 vs 3.9 [95% CI, 2.8-4.6] months for group 2; HR, 0.80 [95% CI, 0.46-1.41]; P = .44). Overall survival was significantly longer with the combination therapy (5.4 [95% CI, 3.2-6.8] months vs 8.9 [95% CI, 4.8-11.4] months; HR, 0.53 [95% CI, 0.29-0.96], P = .03). Adverse event profiles were similar between the 2 groups (eg, grade 3 or 4 thrombocytopenia, 11 of 20 [55%] vs 20 of 40 [50%], and any grade nausea, 9 of 20 [45%] vs 14 of 40 [35%])., Conclusions and Relevance: In this randomized clinical trial, treatment with berzosertib plus topotecan did not improve PFS compared with topotecan therapy alone among patients with relapsed SCLC. However, the combination treatment significantly improved OS., Trial Registration: ClinicalTrials.gov Identifier: NCT03896503. more...
- Published
- 2023
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211. Systemic Therapy for Tumor Control in Metastatic Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors: ASCO Guideline.
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Del Rivero J, Perez K, Kennedy EB, Mittra ES, Vijayvergia N, Arshad J, Basu S, Chauhan A, Dasari AN, Bellizzi AM, Gangi A, Grady E, Howe JR, Ivanidze J, Lewis M, Mailman J, Raj N, Soares HP, Soulen MC, White SB, Chan JA, Kunz PL, Singh S, Halfdanarson TR, Strosberg JR, and Bergsland EK more...
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- Humans, Everolimus therapeutic use, Somatostatin, Sunitinib, Intestinal Neoplasms drug therapy, Neuroendocrine Tumors drug therapy, Neuroendocrine Tumors pathology, Pancreatic Neoplasms drug therapy, Stomach Neoplasms drug therapy, Practice Guidelines as Topic
- Abstract
Purpose: To develop recommendations for systemic therapy for well-differentiated grade 1 (G1) to grade 3 (G3) metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs)., Methods: ASCO convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice., Results: Eight randomized controlled trials met the inclusion criteria for the systematic review., Recommendations: Somatostatin analogs (SSAs) are recommended as first-line systemic therapy for most patients with G1-grade 2 (G2) metastatic well-differentiated GI-NETs. Observation is an option for patients with low-volume or slow-growing disease without symptoms. After progression on SSAs, peptide receptor radionuclide therapy (PRRT) is recommended as systematic therapy for patients with somatostatin receptor (SSTR)-positive tumors. Everolimus is an alternative second-line therapy, particularly in nonfunctioning NETs and patients with SSTR-negative tumors. SSAs are standard first-line therapy for SSTR-positive pancreatic (pan)NETs. Rarely, observation may be appropriate for asymptomatic patients until progression. Second-line systemic options for panNETs include PRRT (for SSTR-positive tumors), cytotoxic chemotherapy, everolimus, or sunitinib. For SSTR-negative tumors, first-line therapy options are chemotherapy, everolimus, or sunitinib. There are insufficient data to recommend particular sequencing of therapies. Patients with G1-G2 high-volume disease, relatively high Ki-67 index, and/or symptoms related to tumor growth may benefit from early cytotoxic chemotherapy. For G3 GEP-NETs, systemic options for G1-G2 may be considered, although cytotoxic chemotherapy is likely the most effective option for patients with tumor-related symptoms, and SSAs are relatively ineffective. Qualifying statements are provided to assist with treatment choice. Multidisciplinary team management is recommended, along with shared decision making with patients, incorporating their values and preferences, potential benefits and harms, and other characteristics and circumstances, such as comorbidities, performance status, geographic location, and access to care.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines. more...
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- 2023
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212. Review of practice informing data and current state of NCCN consensus guidelines in hepatobiliary cancers.
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Corbett V, Li D, and Chauhan A
- Abstract
Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-23-372/coif). VC reports K12 Paul Calabresi Award in Clinical Oncology and he formerly owned equity in Pfizer, BristolMyers Squibb, Seagen, and Viatris, which are outside the submitted work. DL reports grants from Brooklyn Immunotherapeutics and AstraZeneca, consulting fees from Adagene, AstraZeneca, Eisai, Exelixis, Genentech, Ipsen Biopharmaceuticals, Merck, QED, DelCath, TerSera Therapeutics, Sumitomo, TransThera, honorium from Coherus, Servier, Eisai, Exelixis, Ipsen, TerSera and support for attending meetings and/or travel from Genentech. The other author has no conflicts of interest to declare. more...
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- 2023
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213. Prescribing Characteristics of Octreotide Immediate-Release and Long-Acting Release in Patients with Neuroendocrine Tumors.
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Cheng Y, Anthony L, Delcher C, Moga DC, Chauhan A, Huang B, and Adams V
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- Humans, Octreotide therapeutic use, Antineoplastic Agents, Hormonal, Retrospective Studies, Neuroendocrine Tumors drug therapy, Neuroendocrine Tumors pathology, Malignant Carcinoid Syndrome drug therapy
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Background: Treatment recommendations for patients with neuroendocrine tumors (NETs) include the use of octreotide long-acting release (LAR) for long-term therapy and immediate-release (IR) as rescue therapy to control the breakthrough symptoms of carcinoid syndrome (CS). High doses of LAR are commonly used in clinical practice. This study aimed to evaluate the real-world utilization of LAR and preceding IR use at the prescription and patient levels., Methods: We used an administrative claims database (2009-2018) containing privately insured enrollees. We calculated the normalized LAR dose from pharmacy claims and the initial mean IR daily dose at the prescription level. At the patient level, we conducted a retrospective cohort study that included patients continuously enrolled with ≥1 pharmacy claim of LAR and evaluated the frequency and the clinical reason for dose escalation of LAR. The definition of the above-label maximum dose of LAR was ≥30 mg/4 weeks., Results: Nineteen percent of LAR prescriptions had an above-label maximum dose. Only 7% of LAR prescriptions had preceding IR use. There were 386 patients with NETs or CS vs. 570 with an unknown diagnosis. Comparing patients with NETs or CS to those with an unknown diagnosis, 22.3% vs. 11.0 % experienced dose escalations and 29.0% vs. 26.6% had IR use before dose escalation, respectively. LAR dose escalation occurred in 50.9% vs. 39.2% for symptom control, 12.3% vs. 7.1% for tumor progression control, and 16.6% vs. 6.0% for both reasons in NETs/CS and unknown groups, respectively., Conclusion: Octreotide LAR dosing above the label-maximum dose is common and IR rescue dosing appears to be underutilized., (© The Author(s) 2023. Published by Oxford University Press.) more...
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- 2023
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214. Comments on: Comparison of the effectiveness of amblyopia treatment with eye-patch and binocular Occlu-tab for the same treatment duration.
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Sapra H, Chauhan A, Sutar S, and Chaurasiya RK
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- Humans, Duration of Therapy, Visual Acuity, Treatment Outcome, Vision, Binocular, Amblyopia therapy
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Competing Interests: None
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- 2023
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215. Treatment Sequencing Strategies in Advanced Neuroendocrine Tumors: A Review.
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Chauhan A, Del Rivero J, Ramirez RA, Soares HP, and Li D
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Neuroendocrine tumor (NET) incidence has grown. The treatment landscape for advanced NETs is rapidly evolving, but there are limited head-to-head data to guide treatment sequencing decisions. We assessed the available clinical data to aid practicing clinicians in their routine clinical decision-making. Clinical trials have demonstrated efficacy benefits for new therapies in advanced NETs. Emerging long-term data from these trials have enabled clinicians to make more accurate risk-benefit assessments, particularly for patients receiving multiple lines of therapy. However, clinical data specifically regarding treatment sequencing are limited. In lieu of definitive data, treatment sequencing should be based on disease-related factors (e.g., site of tumor origin, volume of disease) and patient-related characteristics (e.g., comorbidities, patient preferences). Clinical decision-making in advanced NETs remains highly individualized and complex; important evidence gaps regarding treatment sequencing remain. Given this, advanced NET management should be a joint effort of multidisciplinary teams at referring and high-volume centers. Additional clinical trial and real-world evidence are needed to meet the challenge of understanding how to sequence available NET therapies. Until these trials are conducted, the best practices provided in this review may serve as a guide for clinicians making treatment sequencing decisions based on the available data. more...
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- 2022
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216. Real-World Clinical and Patient-Reported Outcomes from the Longitudinal Telotristat Ethyl Treatment Registry of Patients with Neuroendocrine Tumors.
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Li D, Darden C, Osman N, Sayeed S, Jackson L, Garbinsky D, and Chauhan A
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Background: Telotristat ethyl (TE) is an oral tryptophan hydroxylase inhibitor approved for the treatment of carcinoid syndrome diarrhea (CSD) in combination with somatostatin analogs (SSAs)., Methods: This prospective, observational, single-arm study evaluated long-term patient-reported outcomes for adults initiating TE in US clinical practice from 2017 through January 2022. The primary objective was satisfaction with overall CS symptom control 6 months after initiating TE. Secondary objectives evaluated satisfaction with control of CSD, flushing, and CS symptoms, as well as work productivity/activity impairment, SSA use, and weight. All analyses were descriptive in nature., Results: A total of 223 patients completed the baseline survey; 56% also completed the 6-month follow-up survey. Mean age was 61 years and 61% were women. After 6 months of TE treatment, the majority of patients (76%, n=95/125) reported being satisfied with control of their CS symptoms which was markedly improved from baseline (41%, n=91). Similarly, the majority of patients (78%, n=97/125) were satisfied with control of their CSD after 6 months of TE, markedly improved from baseline (36%)., Conclusion: This longitudinal observational study showed improvements in real-world clinical and humanistic outcomes for patients with CS and at least 6 months of TE treatment., Competing Interests: D.L. reports research funding to his institution from AstraZeneca and Brooklyn ImmunoTherapeutics. He serves as a consultant and has received honoraria from Adagene, Advanced Accelerator Applications, Coherus BioSciences, Eisai, Exelixis, Genentech, Ipsen Biopharmaceuticals, Lexicon Pharmaceuticals, Merck, MiNA Therapeutics, QED Therapeutics, Servier, Sun Pharma, TerSera Therapeutics, and Delcath. A.C. reports research support from Bristol Myers Squibb, Clovis, Nanotherapeutics, TerSera Therapeutics, Lexicon Pharmaceuticals, and ECS Progastrin. He has served as an advisor to TerSera Therapeutics, Lexicon Pharmaceuticals, Novartis, Ipsen, and Crinetics. C.D., L.J. and D.G. are employees of RTI Health Solutions which received research funding for this study from TerSera Therapeutics. S.S., J.C., and N.O. are employees and shareholders of TerSera Therapeutics. The authors report no other conflicts of interest in this work., (© 2022 Li et al.) more...
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- 2022
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217. Pediatric Neuroendocrine Neoplasms: Rare Malignancies with Incredible Variability.
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Castle JT, Levy BE, and Chauhan A
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Neuroendocrine neoplasms (NENs) encompass a variety of neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) which can arise anywhere in the body. While relatively rare in the pediatric population, the incidence of NENs has increased in the past few decades. These neoplasms can be devastating if not diagnosed and treated early, however, symptoms are variable and can be indolent for many years. There is a reported median of 10 years from the appearance of the first symptoms to time of diagnosis. Considering some of these neoplasms have a mortality rate as high as 90%, it is crucial healthcare providers are aware of NENs and remain vigilant. With better provider education and easily accessible resources for information about these neoplasms, awareness can be improved leading to earlier disease recognition and diagnosis. This manuscript aims to provide an overview of both the most common NENs as well as the rarer NENs with high lethality in the pediatric population. This review provides up to date evidence and recommendations, encompassing recent changes in classification and advances in treatment modalities, including recently completed and ongoing clinical trials. more...
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- 2022
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218. Evolving role of seneca valley virus and its biomarker TEM8/ANTXR1 in cancer therapeutics.
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Corbett V, Hallenbeck P, Rychahou P, and Chauhan A
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Oncolytic viruses have made a significant inroad in cancer drug development. Numerous clinical trials are currently investigating oncolytic viruses both as single agents or in combination with various immunomodulators. Oncolytic viruses (OV) are an integral pillar of immuno-oncology and hold potential for not only delivering durable anti-tumor responses but also converting "cold" tumors to "hot" tumors. In this review we will discuss one such promising oncolytic virus called Seneca Valley Virus (SVV-001) and its therapeutic implications. SVV development has seen seismic evolution over the past decade and now boasts of being the only OV with a practically applicable biomarker for viral tropism. We discuss relevant preclinical and clinical data involving SVV and how bio-selecting for TEM8/ANTXR1, a negative tumor prognosticator can lead to first of its kind biomarker driven oncolytic viral cancer therapy., Competing Interests: PH was employed by Seneca Therapeutics Inc. VC formerly owned equity in Pfizer, BristolMyers Squibb, Seagen, and Viatris. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Corbett, Hallenbeck, Rychahou and Chauhan.) more...
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- 2022
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219. Comprehensive Assessment of Somatostatin Receptors in Various Neoplasms: A Systematic Review.
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Priyadarshini S, Allison DB, and Chauhan A
- Abstract
Somatostatin receptors (SSTR) are expressed in various neoplasms and can be targeted for both diagnostics as well as therapeutics. This systematic review aims to compile and discuss the prevalence of somatostatin receptor expression in various neoplasms. We performed a literature search from Google Scholar and PubMed using relevant keywords to look for all publicly available data regarding SSTR expression in various cancers. Both histopathological and radiographical studies were included for SSTR assessment. We found that many cancers express SSTR with varying prevalence. SSTR is now a well-established theranostics biomarker. We now have highly sensitive and specific diagnostic modalities like gallium 68 DOTATATE and copper 64 DOTATATE scans to screen for SSTR-2 and then target it therapeutically with lutetium 177 DOTATATE. A thorough understanding of SSTR expression in other tumors will open the channels for exploring potential SSTR targeting. more...
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- 2022
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220. An Update on the Management of Mixed Neuroendocrine-Non-neuroendocrine Neoplasms (MiNEN).
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Jacob A, Raj R, Allison DB, Soares HP, and Chauhan A
- Subjects
- Chemotherapy, Adjuvant, Humans, Infant, Newborn, Retrospective Studies, Gastrointestinal Neoplasms, Neuroendocrine Tumors diagnosis, Neuroendocrine Tumors etiology, Neuroendocrine Tumors therapy, Pancreatic Neoplasms pathology
- Abstract
Opinion Statement: The classification of mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) is evolving, and no clear management guidelines are currently available. However, recent studies provide insight into factors affecting outcomes and could help develop treatment decisions for patients with these rare malignancies. The majority of MiNENs have a poorly differentiated neuroendocrine carcinoma (NEC) component which is associated with an aggressive clinical course and poor outcomes. Due to the paucity of clinical trials, strategies adopted in gastrointestinal cancers and NECs are used to manage MiNENs. It is also to be noted that the thoracic neuroendocrine neoplasm WHO 2021 classification does not recognize MiNEN terminology but suggests an equivalent terminology called "combined neuroendocrine non neuroendocrine neoplasm." Surgical management is appropriate in early-stage disease with a low threshold for addition of adjuvant chemotherapy. Multimodality treatment with chemotherapy offers a survival benefit in advanced disease or when surgical resection is not possible without significant morbidity. Chemotherapy should be directed at the more aggressive component which is often the NEC component. In addition, molecular testing should be employed to evaluate patients for enrollment in clinical trials and other targeted treatments. Being a rare disease with retrospective studies and case series providing the majority of data on treatment selection, it is essential to include more granular details of pathology (e.g., Ki-67, mitotic index, percentage of each component, staging information) and treatment modalities (e.g., type and duration, rationale, radiologic response, survival outcomes) in future studies to make systematic reviews possible and help derive meaningful conclusions., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.) more...
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- 2022
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221. External Validation of a Clinical Score for Patients With Neuroendocrine Tumors Under Consideration for Peptide Receptor Radionuclide Therapy.
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Das S, Chauhan A, Du L, Thomas KE, Jacob A, Schad A, Jain S, Jessop A, Shah C, Eisner D, Cardin DB, Ciombor KK, Goff LW, Bradshaw M, Delbeke D, Sandler M, Ramirez RA, and Berlin J
- Subjects
- Aged, Cohort Studies, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Octreotide analogs & derivatives, Octreotide therapeutic use, Organometallic Compounds therapeutic use, Predictive Value of Tests, Prognosis, Progression-Free Survival, Proportional Hazards Models, Prospective Studies, Radionuclide Imaging, Treatment Outcome, Neuroendocrine Tumors mortality, Neuroendocrine Tumors radiotherapy, Radioisotopes therapeutic use, Receptors, Peptide therapeutic use, Severity of Illness Index
- Abstract
Importance: Despite the benefit of peptide receptor radionuclide therapy (PRRT) for patients with well-differentiated neuroendocrine tumors (WD NETs), no clinical metric to anticipate benefit from the therapy for individual patients has been previously defined., Objective: To assess whether the prognostic ability of the clinical score (CS) could be validated in an external cohort of patients with WD NETs., Design, Setting, and Participants: This multicenter cohort study's analysis included patients with WD NETs who were under consideration for peptide receptor radionuclide therapy (PRRT) with lutetium-177 (177Lu)-dotatate between March 1, 2016, and March 17, 2020. The original cohort included patients from Vanderbilt-Ingram Cancer Center. The validation cohort included patients from Ochsner Medical Center, Markey Cancer Center, and Rush Medical Center. Patients with paragangliomas, pheochromocytomas and neuroblastomas were excluded. Statistical analysis was performed from June to November 2021., Exposures: PRRT with 177Lu-dotatate or alternate therapies such as everolimus, sunitinib, or capecitabine plus temozolomide., Main Outcomes and Measures: The primary outcome was progression-free survival (PFS) and was estimated by the Kaplan-Meier method; a Cox proportional-hazards model adjusting for primary tumor site, tumor grade, and number of PRRT doses administered was used to analyze association between CS and outcomes., Results: A total of 126 patients (median age [IQR] age: 63.6 [52.9-70.7] years; 64 male individuals) were included in the validation cohort, and the combined cohort (validation and original cohorts combined) had a total of 248 patients (median [IQR] patient age: 63.3 [53.3-70.3] years; 126 male individuals). In the validation cohort, on multivariable analysis, for each 2-point increase in CS, PFS decreased significantly (hazard ratio, 2.61; 95% CI, 1.64-4.16). After finding an association of the CS with PFS in the validation cohort, the original and validation cohorts were combined into the cohort for this analysis. On multivariable analysis, for each 2-point increase in CS, PFS decreased significantly (hazard ratio, 2.52; 95% CI, 1.89-3.36)., Conclusions and Relevance: Increases in CS were associated with worsening PFS in the validation cohort, validating findings from the original cohort. These findings suggest that the CS, to our knowledge, represents the first clinical metric to estimate anticipated benefit from PRRT for patients with WD NETs and may be a clinical tool for patients being considered for PRRT. more...
- Published
- 2022
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222. 68 Ga-DOTATATE PET/CT: The Optimum Standardized Uptake Value (SUV) Internal Reference.
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Ragab A, Wu J, Ding X, Clark A, Mischen B, Chauhan A, Oates ME, Anthony L, and El Khouli R
- Subjects
- Gallium Radioisotopes, Humans, Positron-Emission Tomography, Radionuclide Imaging, Radiopharmaceuticals, Reproducibility of Results, Retrospective Studies, Organometallic Compounds, Positron Emission Tomography Computed Tomography
- Abstract
Rationale and Objectives: Standardized Uptake Value (SUV) is an important semiquantitative measurement used in the clinical and research domains to assess radiopharmaceutical concentration in tumors versus normal organs, but is susceptible to many factors beyond the tumor biological environment. So, the aim of this study is to identify the optimum internal reference among organs with physiological uptake in
68 Ga-DOTATATE PET/CT (DOTA PET/CT) scans., Materials and Methods: This HIPAA-compliant, IRB-approved study with waiver of consent included retrospective imaging review of 180 consecutive patients with neuroendocrine tumors presenting for DOTA PET/CT image acquisition: Ga-68 DOTATATE dose was reported as (0.054 mCi/Kg) scans between September 2018 and May 2019. Mean value of body weight normalized SUV (SUVbw ) and lean body mass normalized SUV (SUL) of liver and spleen were measured. Information about the patients and scan characteristics were collected. The paired Grambsch test was used to compare variance among the measured SUVs. Spearman's rank correlation coefficient was used to assess correlation between SUVs and potential patient- and scan-specific confounding factors., Results: Variance of SUL was significantly lower than variance of SUVbw in both liver and spleen (p-value < 0.0001). Variances of liver SUVbw and SUL were significantly lower than the corresponding spleen SUVs. Liver SUL showed the lowest variance (3.69% ± 1.25%) among all measured SUVs., Conclusion: SUL is a more reproducible, less variable, and therefore more reliable quantitative measure in DOTA PET/CT scans, compared SUVbw . Among the available organs with physiological uptake, liver SUL is the optimum internal reference given the liver's larger size and uniform SUL values resulting in lower variability and better reproducibility., (Copyright © 2020 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.) more...- Published
- 2022
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223. Can an amino acid mixture alleviate gastrointestinal symptoms in neuroendocrine tumor patients?
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Chauhan A, Das S, Miller R, Luque L, Cheuvront SN, Cloud J, Tarter Z, Siddiqui F, Ramirez RA, and Anthony L
- Subjects
- Adult, Aged, Aged, 80 and over, Diarrhea etiology, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neuroendocrine Tumors drug therapy, Retrospective Studies, Treatment Outcome, Amino Acids administration & dosage, Diarrhea drug therapy, Neuroendocrine Tumors complications, Rehydration Solutions administration & dosage
- Abstract
Background: Neuroendocrine tumors, although relatively rare in incidence, are now the second most prevalent gastrointestinal neoplasm owing to indolent disease biology. A small but significant sub-group of neuroendocrine tumor patients suffer from diarrhea. This is usually secondary to carcinoid syndrome but can also be a result of short gut syndrome, bile acid excess or iatrogenic etiologies. Recently, an amino acid based oral rehydration solution (enterade® Advanced Oncology Formula) was found to have anti-diarrheal properties in preclinical models., Methods: A retrospective chart review of all NET patients treated with enterade® AO was performed after IRB approval., Results: Ninety-eight NET patients who had received enterade® AO at our clinic from May 2017 through June 2019 were included. Patients (N = 49 of 98) with follow up data on bowel movements (BMs) were included for final analysis. Eighty-four percent of patients (41/49) had fewer BMs after taking enterade® AO and 66% (27/41) reported more than 50% reduction in BM frequency. The mean number of daily BMs was 6.6 (range, 3-20) at baseline before initiation of therapy, while the mean number of BMs at 1 week time point post enterade® AO was 2.9 (range, 0-11)., Conclusions: Our retrospective observations are encouraging and support prospective validation with appropriate controls in NET patients. This is first published report of the potential anti-diarrheal activity of enterade® AO in NET patients. more...
- Published
- 2021
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224. Immunotherapy for Medulloblastoma: Current Perspectives.
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Kabir TF, Kunos CA, Villano JL, and Chauhan A
- Abstract
Background: Immune-mediated therapies have transformed the treatment of metastatic melanoma and renal, bladder, and both small and non-small cell lung carcinomas. However, immunotherapy is yet to demonstrate dramatic results in brain tumors like medulloblastoma for a variety of reasons. Recent pre-clinical and early phase human trials provide encouraging results that may overcome the challenges of central nervous system (CNS) tumors, which include the intrinsic immunosuppressive properties of these cancers, a lack of antigen targets, antigenic variability, and the immune-restrictive site of the CNS. These studies highlight the growing potential of immunotherapy to treat patients with medulloblastoma, a disease that is a frequent cause of morbidity and mortality to children and young adults., Methods: We conducted an inclusive review of the PubMed-indexed literature and studies listed in clinicaltrials.gov using combinations of the keywords medulloblastoma, immunotherapy, CNS tumors, brain tumors, vaccines, oncolytic virus, natural killer, and CAR T to identify trials evaluating immunotherapy in preclinical experiments or in patients with medulloblastoma. Given a limited number of investigations using immunotherapy to treat patients with medulloblastoma, 24 studies were selected for final analysis and manuscript citation., Results: This review presents results from pre-clinical studies in medulloblastoma cell lines, animal models, and the limited trials involving human patients., Conclusion: From our review, we suggest that cancer vaccines, oncolytic viral therapy, natural killer cells, and CAR T therapy hold promise against the innate immunosuppressive properties of medulloblastoma in order to prolong survival. There is an unmet need for immunotherapy regimens that target overexpressed antigens in medulloblastoma tumors. We advocate for more combination treatment clinical trials using conventional surgical and radiochemotherapy approaches in the near-term clinical development., Competing Interests: Dr Aman Chauhan reports grants from BMS and Clovis, during the conduct of the study. The authors report no other conflicts of interest in this work., (© 2020 Kabir et al.) more...
- Published
- 2020
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225. Biliary tract large cell neuroendocrine carcinoma: current evidence.
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Raiker R, Chauhan A, Hasanein H, Burkeen G, Horn M, Veedu J, Vela C, Arnold S, Kolesar J, Anthony L, Evers BM, and Cavnar M
- Subjects
- Aged, Biliary Tract metabolism, Biliary Tract pathology, Carcinoma, Large Cell metabolism, Carcinoma, Neuroendocrine metabolism, Female, Humans, Male, Middle Aged, Prognosis, Carcinoma, Large Cell pathology, Carcinoma, Neuroendocrine pathology
- Abstract
Background: Primary neuroendocrine carcinomas of the gallbladder and biliary tract are rare, with pure large cell neuroendocrine carcinomas (LCNEC) being exceedingly rare and with a particularly poor prognosis., Methods: We performed a review of published data on biliary tract large cell neuroendocrine carcinomas in PubMed., Results: Preliminary search revealed over 2000 results but we found only 12 cases of pure large cell neuroendocrine carcinomas of biliary tract noted in literature to date. Because it commonly presents with non-specific symptoms of abdominal pain and jaundice, diagnosis is made after resection with histo-pathological and immunohistochemical analysis. These cancers are particularly aggressive with high recurrence rates, most often presenting with metastasis to regional lymph nodes and/or the liver resulting in a poor prognosis. Overall, complete surgical excision with systemic chemotherapy is the treatment mainstay. If the cancer is unresectable due to multiple metastases, medical management with systemic chemotherapy is the primary treatment modality., Conclusion: The prognosis of hepatobiliary LCNEC remains poor with median survival of only 11 months from initial diagnosis. Studies focusing on high grade neuroendocrine carcinoma are needed to enhance our understanding of biology and therapeutics in this rare but aggressive cancer. more...
- Published
- 2019
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226. Can a High-grade Neuroendocrine Carcinoma be Functional?
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Graham C, Chauhan A, and Anthony L
- Subjects
- Fatal Outcome, Female, Humans, Liver diagnostic imaging, Middle Aged, Neoplasm Grading, Neoplasm Staging, Patient Selection, Tomography, X-Ray Computed methods, Carcinoma, Neuroendocrine metabolism, Carcinoma, Neuroendocrine pathology, Ki-67 Antigen analysis, Pancreas diagnostic imaging, Pancreas metabolism, Pancreatic Neoplasms metabolism, Pancreatic Neoplasms pathology, Vasoactive Intestinal Peptide metabolism
- Abstract
We present a rare high-grade, functional, neuroendocrine carcinoma of the pancreas secreting vasoactive intestinal peptide. This case is unique, given the tumor's aggressive features and high Ki-67 index while also secreting functional hormones, which is unusual in high-grade neuroendocrine tumors (NETs). Our patient initially presented with diarrhea and was found to have a 4.7 × 3.1 × 3.3 cm pancreatic mass with diffuse hepatic metastasis staining positive for vasoactive intestinal peptide, chromogranin A and synaptophysin. She was initially underscored as grade 2 NET due to low mitosis, but subsequently restaged based on Ki-67 index as a grade 3 neuroendocrine carcinoma. She unfortunately was not a candidate for chemotherapy at that time. We conclude that high-grade NETs have the potential to secrete active peptide hormones. We therefore recommend that NETs with aggressive features be biopsied and assessed for Ki-67 activity and mitosis regardless if they are functional tumors, with goal for early initiation of chemotherapy., (Copyright © 2018. Published by Elsevier Inc.) more...
- Published
- 2019
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227. Management of Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia: Review and a Single Center Experience.
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Myint ZW, McCormick J, Chauhan A, Behrens E, and Anthony LB
- Subjects
- Aged, Anti-Bacterial Agents therapeutic use, Antineoplastic Agents, Hormonal therapeutic use, Azithromycin therapeutic use, Bronchial Neoplasms complications, Carcinoid Tumor complications, Cough etiology, Dyspnea etiology, Everolimus therapeutic use, Female, Humans, Hyperplasia complications, Hyperplasia drug therapy, Hyperplasia physiopathology, Immunosuppressive Agents therapeutic use, Lung Diseases complications, Lung Diseases physiopathology, Male, Middle Aged, Multiple Pulmonary Nodules complications, Multiple Pulmonary Nodules drug therapy, Multiple Pulmonary Nodules physiopathology, Octreotide therapeutic use, Pulmonary Disease, Chronic Obstructive complications, Pulmonary Fibrosis complications, Quality of Life, Lung Diseases drug therapy, Neuroendocrine Cells pathology, Respiratory Mucosa pathology
- Abstract
Background: Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare pulmonary condition, characterized by diffuse proliferation of neuroendocrine cells in the respiratory epithelium. DIPNECH lesions are less than 5 mm in size and are limited to the basement membrane with no invasion. There is limited information regarding epidemiology, natural history of disease progression, or the management of this rare entity. We present the experience of a center with extensive expertise in neuroendocrine disease., Methods: A cohort of patients (N = 13) with DIPNECH treated and followed at our institution was identified. We describe the our approach to their care, our disease management and also provide a review of DIPNECH pathophysiology., Results: Our patient cohort consisted of twelve females and one male with a mean age of 63 years at the time of diagnosis. Dyspnea on exertion and dry cough were the most common presenting symptoms. Two patients were under surveillance without treatment; three patients were treated with a short-acting somatostatin analog; three patients were treated with azithromycin alone; four were treated with a combination of long-acting monthly somatostatin analogs and azithromycin; one patient received a combination of long-acting somatostatin analog and everolimus. Five patients had concomitant bronchial carcinoids., Conclusions: DIPNECH is a rare pathology that can profoundly affect a patient's quality of life. Paroxysmal coughing episodes can be difficult to treat. Our limited single center experience shows encouraging response to use of somatostatin analogs, azithromycin, and everolimus in the management of debilitating DIPNECH associated symptoms. more...
- Published
- 2018
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228. Management of pulmonary neuroendocrine tumors.
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Ramirez RA, Chauhan A, Gimenez J, Thomas KEH, Kokodis I, and Voros BA
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- Humans, Lung Neoplasms drug therapy, Lung Neoplasms radiotherapy, Neuroendocrine Tumors drug therapy, Neuroendocrine Tumors radiotherapy, Lung Neoplasms therapy, Neuroendocrine Tumors therapy
- Abstract
Neuroendocrine tumors (NETs) of the lung are divided into 4 major types: small cell lung cancer (SCLC), large cell neuroendocrine carcinoma (LCNEC), atypical carcinoid (AC) or typical carcinoid (TC). Each classification has distinctly different treatment paradigms, making an accurate initial diagnosis essential. The inconsistent clinical presentation of this disease, however, makes this difficult. The objective of this manuscript is to detail the diagnosis and management of the well differentiated pulmonary carcinoid (PC) tumors. A multidisciplinary approach to work up and treatment should be utilized for each patient. A multimodal radiological work-up is used for diagnosis, with contrast enhanced CT predominantly utilized and functional imaging techniques. A definitive diagnosis is based on tissue findings. Surgical management remains the mainstay of therapy and can be curative. In those with advanced disease, medical treatments consist of somatostatin analog (SSA) therapy, targeted therapy, chemotherapy or peptide receptor radionuclide therapy. SSAs are the standard of care in those with metastatic NETs, using either Octreotide long acting repeatable (LAR) or lanreotide as reasonable options, despite a scarcity of prospective data in PCs. Targeted therapies consist of everolimus which is approved for use in PCs, with various studies showing mixed results with other targeted agents. Additionally, radionuclide therapy may be used and has been shown to increase survival and to reduce symptoms in some studies. Prospective trials are needed to determine other strategies that may be beneficial in PCs as well as sequencing of therapy. Successful diagnosis and optimal treatment relies on a multidisciplinary approach in patients with lung NETs. Clinical trials should be used in appropriate patients. more...
- Published
- 2017
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229. Neuroendocrine tumors (NETs) of unknown primary: is early surgical exploration and aggressive debulking justifiable?
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Wang YZ, Chauhan A, Rau J, Diebold AE, Opoku-Boateng A, Ramcharan T, Boudreaux JP, and Woltering EA
- Subjects
- Adult, Aged, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neoplasm Grading, Neoplasms, Unknown Primary pathology, Neuroendocrine Tumors pathology, Prognosis, Retrospective Studies, Survival Rate, Cytoreduction Surgical Procedures methods, Neoplasms, Unknown Primary surgery, Neuroendocrine Tumors surgery
- Abstract
Background: Neuroendocrine tumors (NETs) are rare tumors that often present with vague symptoms. Identification and localization of the primary NET can be challenging and the true incidence remains unclear. These patients have been thought to have a poor prognosis compared to those patients with a known primary. Therefore, traditionally the treatments for patients with unknown primaries have been passive and directed towards symptom control and/or cytoreduction of metastatic disease. We hypothesized that NET of unknown primary are predominantly low-grade and easily located surgically and therefore are amendable to surgical debulking and cytoreduction, which will likely increase survival in these patients., Methods: The charts for all 342 surgical patients, seen in our clinic at Ochsner-Kenner between 1/2009 and 9/2012 were retrospectively reviewed to determine which patients had a pre-operative diagnosis of a "NET with unknown primary". Twenty-two patients (6.4%) were identified. For these patients, the rate of successful surgical exploration in which a primary site was identified was recorded. Survival for these "unknown primary" patients were compared to a large similar group of NET patients from a recent study collected from this same Ochsner clinic group., Results: Twenty-two (22/342, 6.4%) NET patients with a pre-operative diagnosis of an unknown primary were explored and cytoreduced. The primary tumor site was identified in all 22 patients (100%). The primary sites identified for these patients were 19 small intestines (86.4%) and 3 pancreatic (13.6%). All 22 patients had low-grade tumors and all were still alive as of 9/2012, not allowing for a survival curve to be generated., Conclusions: Unknown primary NETs are not associated with a poor prognosis as previously reported. Timely surgical exploration and debulking always results in the identification of the primary and a maximum cytoreduction. Early surgical exploration with aggressive debulking is indicated for the treatment of these patients, as for the known counterpart. more...
- Published
- 2016
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230. Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH) and the Role of Somatostatin analogs: A Case Series.
- Author
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Chauhan A and Ramirez RA
- Subjects
- Aged, Antineoplastic Agents, Hormonal adverse effects, Cough etiology, Female, Humans, Hyperplasia complications, Hyperplasia drug therapy, Lung Diseases complications, Middle Aged, Octreotide adverse effects, Precancerous Conditions complications, Retrospective Studies, Somatostatin analogs & derivatives, Antineoplastic Agents, Hormonal therapeutic use, Lung Diseases drug therapy, Neuroendocrine Cells pathology, Octreotide therapeutic use, Precancerous Conditions drug therapy
- Abstract
Objectives: DIPNECH is a rare pre-neoplastic condition that often presents with a variety of non-specific pulmonary symptoms and sometimes seen in conjunction with pulmonary carcinoid tumors. There are very limited data on use of somatostatin analogs in patients with DIPNECH. We review the long-term outcomes of somatostatin analog therapy with regard to symptom control in patients with DIPNECH., Materials/methods: Retrospective study out of our extensive registry of over 2000 neuroendocrine tumors identifies 184 pulmonary neuroendocrine tumors. Out of this, there were five histopathologically confirmed cases of DIPNECH. Appropriate institutional review board permission was taken for this analysis., Results: All 5 patients were females, with a mean age at diagnosis was 65.5 years. Follow-up period includes 1-5 years. Cough was the presenting complaint in all five patients described as mostly dry, except for one patient who had productive early morning cough. Other symptoms seen in one of our patients included wheezing, flushing, and fluctuating blood pressure. No one reported weight loss, hemoptysis, and shortness of breath. One of our patients had a benign thyroid nodule and two patients had previous history of breast cancer. All five of our patients were histopathologically diagnosed by lung biopsy. 4 out of 5 patients were started on a somatostatin analog. All four patients reported drastic improvement in cough. One patient reported mild abdominal discomfort and diarrhea as side effects but remained on treatment., Conclusions: From our single institution review of neuroendocrine pulmonary tumor cases, we found only five cases of DIPNECH, which reaffirms rare nature of the pathology. It primarily affects females over 60 years with dry cough as the most common presenting symptom. Most of our patients responded to treatment with a somatostatin analog and had significant improvement in their presenting symptoms. Somatostatin analogs were well tolerated resulting in significant resolution of presenting symptoms in most of our patients. Further research is needed; however, a trial of somatostatin analogs should be considered in the treatment of patients with DIPNECH with responders being treated long term. more...
- Published
- 2015
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231. Adjuvant intraoperative post-dissectional tumor bed chemotherapy-A novel approach in treating midgut neuroendocrine tumors.
- Author
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Wang YZ, Chauhan A, and Hall MA
- Abstract
Background: Midgut neuroendocrine tumor (NET) patients are often diagnosed at an advanced stage with extensive mesenteric lymph node and liver metastasis. Even with skillful surgical dissection, macro and microscopic residual disease at the dissection site remains a possibility. We hypothesize these potential tumor residuals in mesenteric lymph node dissection beds can be eliminated safely by a local application of 5-fluorouracil (5-FU). We describe a novel technique invented by the author to treat these micro and macro residuals., Methods: Retrospectively, charts of 62 consecutive midgut NET patients with boggy mesenteric lymphadenopathy who underwent cytoreductive debulking surgeries from 1/2007 to 12/2009 were reviewed. A total of 32 patients received an intraoperative application of 5-FU saturated gelfoam strips secured into the mesenteric defect following the extensive lymphadenectomy. A total of 30 untreated patients served as a control., Results: The 5-year survival after cytoreductive surgeries was 22/32 (68.8%) for the treated group, vs. 20/30 (66.7%) for the control. Six patients (6/32, 18.8%) among the study group required additional debulking surgeries, vs. 16 patients (16/30, 53.3%) in the control group. Upon reoperation, loco-regional recurrence was noted in 9 of the 16 patients (56.3%) in the control group, vs. only 2/6 (33.3%) of treated patients. Overall, local recurrence rate is 6.25% (2/32) in the treated group vs. 30% (9/30) in the control group. Post-op complication rates are similar in the two arms., Conclusions: Intraoperative application of chemotherapy is a safe and effective adjuvant to reduce local recurrence and the need of reoperation by the tumoricidal or tumorstatic effects of 5-FU on any potential microscopic residual disease after extensive cytoreductive surgeries in advanced stage NET patients with mesenteric lymph node metastasis. It provides patients with sustained, slow releasing, high dose of 5-FU within the surgical bed with a negligible side effect profile. Further studies are required to evaluate its effect on long term survival. more...
- Published
- 2015
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232. Transition of a pancreatic neuroendocrine tumor from ghrelinoma to insulinoma: a case report.
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Chauhan A, Ramirez RA, Stevens MA, Burns LA, and Woltering EA
- Abstract
Pancreatic neuroendocrine tumors (PNETs) are rare with an incidence of 1 in 100,000 populations. PNETs can present either as a functional or non-functional tumor. In functional tumors the symptoms are a result of hormones such as insulin, gastrin, glucagon and vasoactive intestinal peptide (VIP) or others. Ghrelin is a 28 amino acid peptide discovered in 1999 and is thought to be involved in various physiologic and pathologic processes. Due to relatively recent discovery of this hormone, its functions in normal homeostasis and its association with various pathologic processes are still being uncovered. PNETs are a rare entity and the natural history of disease is not well known. We have presented a first ever case of metastatic PNET which presented as a ghrelinoma and later transformed into a symptomatic insulinoma. This case gives us a glimpse into an unusual variant of metastatic PNET. It also tells us that change in functional tumor biology can sometime be more morbid than the metastatic disease itself. more...
- Published
- 2015
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233. Management of immune thrombocytopenic purpura: an update.
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Warrier R and Chauhan A
- Abstract
Rapid strides have been made in the field of hematology, and advances in immune thrombocytopenic purpura (ITP) management are no exception. From idiopathic to immune, the changed nomenclature is itself a testimonial to the growing awareness and improvements in the management of ITP. We discuss the pathophysiology, clinical presentation, and current management of this common pediatric disorder and summarize current guidelines for ITP treatment. more...
- Published
- 2012
234. Cisplatin and cranial irradiation-related hearing loss in children.
- Author
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Warrier R, Chauhan A, Davluri M, Tedesco SL, Nadell J, and Craver R
- Abstract
Background: High doses of cisplatin and cranial radiotherapy (CRT) have been reported to cause irreversible hearing loss. The objective of this study was to examine the influence of cranial irradiation on cisplatin-associated ototoxicity in children with pediatric malignancies., Methods: Serial audiograms were obtained for 33 children, age <16 years, treated with cisplatin-based chemotherapy (90-120 mg/m(2) per cycle) with or without CRT. Eligible patients included those with normal baseline audiometric evaluations and without significant exposure to other ototoxic drugs. We defined significant hearing loss as a hearing threshold ≥30 dB at 2,000-8,000 Hz frequencies., Results: The median age of our study population was 4.9 years (range 6 weeks to 16 years), and the male to female ratio was 0.8:1. The study population consisted of 15 Caucasians, 17 African-Americans, and 1 Hispanic. Fourteen patients had brain tumors, and 19 had other solid tumors. Thirteen patients were exposed to CRT, and 20 were not. Bilateral hearing loss was observed in 24/33 (73%) patients, with severe/profound (≥70 dB) impairment in 10/33 (30%) of all patients. Young age (<5 years), CRT, and brain tumors were independent prognostic factors predicting hearing loss., Conclusion: The study demonstrated a high incidence of hearing loss in children treated with cisplatin and CRT. Consequently, we recommend monitoring these children for the early detection of hearing loss. more...
- Published
- 2012
235. Younger women are affected by breast cancer in South India - a hospital-based descriptive study.
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Chauhan A, Subba SH, Menezes RG, Shetty BS, Thakur V, Chabra S, and Warrier R
- Subjects
- Adult, Age Factors, Aged, Breast Neoplasms etiology, Female, Follow-Up Studies, Hospitals, Humans, India epidemiology, Middle Aged, Prevalence, Prognosis, Risk Factors, Young Adult, Breast Neoplasms epidemiology
- Abstract
Introduction: Breast cancer is one of the most common cancers in the world among women and its effective control depends upon sufficient knowledge about its epidemiology at the regional as well as global levels., Materials and Methods: A record based descriptive study was conducted in a tertiary care hospital situated in coastal Karnataka in South India. Cases included were all histopathologically diagnosed cases of breast cancer not otherwise specified among females that were treated in the hospital in the 3 years period of 2005-2007. A total of 112 cases were found and their data retrieved and analyzed using SPSS., Results: Mean age of the subjects was 45 years (SD=10.4) (range 23 -70). Age distribution showed two peaks at 35-39 years and 50-54 years. Some 12 (11%) patients had a previous history of breast cancer and 9 (8%) had a family history. Among the patients who had history of breast cancer in the past, 61.5% were during the pre-menopausal age., Conclusion: The age affected by breast cancer was lower than usually seen in other parts of the world and there was more of premenopausal occurrence which has implications on their own and their relatives' chances of acquiring breast cancer later. The findings show that breast cancer control efforts and recommendations in different parts of the world have to be tailored to the regional epidemiological patterns. more...
- Published
- 2011
236. Effective management of pain in pediatric hematology and oncology.
- Author
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Chauhan A, Weiss J, and Warrier R
- Subjects
- Adult, Humans, Hodgkin Disease complications, Kidney Neoplasms complications, Lymphoma, Non-Hodgkin complications, Pain drug therapy, Pain etiology, Precursor Cell Lymphoblastic Leukemia-Lymphoma complications, Wilms Tumor complications
- Abstract
In the last several decades, there have been major advances in the treatment of pediatric cancers. 5 year survival of children with acute lymphoblastic leukemia has increased from 25% to 80%. Early stages of non -Hodgkin's, Hodgkin's and Wilms tumors all have more than 90% long term survival. In addition to improving survival, the comprehensive care of children with cancer must offer total care including special emphasis on pain management and psychosocial support by a multidisciplinary team. Pain considerations in children are unique and differ from those in adults. For example, bone pain is often one of the presenting symptoms of leukemia in children, but can be mistaken for growing pain or labeled psychological. Bone pain is also a prominent symptom in late stage neuroblastoma, and of course in bone tumors. The American Medical Association and National Cancer Institute promote the absence of pain as a patient right and a marker of good clinical care and a quality of care issue. Pain due to disease burden responds dramatically to chemotherapy and the uninitiated are often surprised by the sudden increase in activity and playfulness of children undergoing induction chemotherapy. History and physical data, with special assessment of pain should be part of the medical record of all children. more...
- Published
- 2010
237. Inflammatory myofibroblastic tumor mimics an abdominal neoplasm.
- Author
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Sambhaji CJ, Chauhan A, and Kakkar C
- Published
- 2009
238. Prognostic value of prolactin in postoperative colorectal carcinoma.
- Author
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Chauhan A, Kurian J, Kakria A, Kanchan T, and Menezes RG
- Published
- 2008
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