7 results on '"Srirajaskanthan, Rajaventhan"'
Search Results
2. Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate: an analysis of the NETTER-1 study
- Author
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Strosberg, Jonathan, Kunz, Pamela L, Hendifar, Andrew, Yao, James, Bushnell, David, Kulke, Matthew H, Baum, Richard P, Caplin, Martyn, Ruszniewski, Philippe, Delpassand, Ebrahim, Hobday, Timothy, Verslype, Chris, Benson, Al, Srirajaskanthan, Rajaventhan, Pavel, Marianne, Mora, Jaume, Berlin, Jordan, Grande, Enrique, Reed, Nicholas, Seregni, Ettore, Paganelli, Giovanni, Severi, Stefano, Morse, Michael, Metz, David C, Ansquer, Catherine, Courbon, Frédéric, Al-Nahhas, Adil, Baudin, Eric, Giammarile, Francesco, Taïeb, David, Mittra, Erik, Wolin, Edward, O’Dorisio, Thomas M, Lebtahi, Rachida, Deroose, Christophe M, Grana, Chiara M, Bodei, Lisa, Öberg, Kjell, Polack, Berna Degirmenci, He, Beilei, Mariani, Maurizio F, Gericke, Germo, Santoro, Paola, Erion, Jack L, Ravasi, Laura, and Krenning, Eric
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Digestive Diseases ,Clinical Research ,Clinical Trials and Supportive Activities ,Cancer ,Alkaline Phosphatase ,Humans ,Liver Neoplasms ,Neuroendocrine Tumors ,Octreotide ,Organometallic Compounds ,Treatment Outcome ,NETTER-1 study group ,177Lu-Dotatate ,Liver tumour burden ,NETTER-1 ,Neuroendocrine tumour ,Other Physical Sciences ,Clinical Sciences ,Nuclear Medicine & Medical Imaging ,Clinical sciences - Abstract
PurposeTo assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate.MethodsIn the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression.ResultsSignificantly prolonged median PFS occurred with 177Lu-Dotatate versus octreotide LAR 60 mg in patients with low ( 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the 177Lu-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden.Conclusions177Lu-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. Clinicaltrials.gov : NCT01578239, EudraCT: 2011-005049-11.
- Published
- 2020
3. Genetic and epigenetic prognosticators of neuroendocrine tumours of the GI tract, liver, biliary tract and pancreas: A systematic review and meta‐analysis.
- Author
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Mestre‐Alagarda, Claudia, Srirajaskanthan, Rajaventhan, Zen, Yoh, Giwa, Mojisola, Howard, Mark, and Ooft, Marc Lucas
- Subjects
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GASTROINTESTINAL system , *BILIARY tract , *NEUROENDOCRINE tumors , *PANCREAS , *SINGLE nucleotide polymorphisms , *GALLBLADDER , *INTRAHEPATIC bile ducts - Abstract
Multiple recurrent genetic and epigenetic aberrations have been associated with worse prognosis in multiple studies of neuroendocrine tumours (NETs), but these have been mainly small cohorts and univariate analysis. This review and meta‐analysis will focus upon the literature available on NETs of the gastrointestinal (GI) tract, liver, biliary tract and pancreas. PubMed and Embase were searched for publications that investigated the prognostic value of (epi)genetic changes of neuroendocrine tumours. A meta‐analysis was performed assessing the association of the (epi)genetic alterations with overall survival (OS), disease‐free survival (DFS) or locoregional control (LRC). In the pancreas DAXX/ATRX [hazard ratio (HR) = 3.29; 95% confidence interval (CI) = 2.28–4.74] and alternative lengthening telomeres (ALT) activation (HR = 8.20; 95% CI = 1.40–48.07) showed a pooled worse survival. In the small bowel NETs gains on chromosome 14 were associated with worse survival (HR 2.85; 95% CI = 1.40–5.81). NETs from different anatomical locations must be regarded as different biological entities with diverging molecular prognosticators, and epigenetic changes being important to the pathogenesis of these tumours. This review underpins the prognostic drivers of pancreatic NET which lie in mutations of DAXX/ATRX and ALT pathways. However, there is reaffirmation that prognostic molecular biomarkers of small bowel NETs should be sought in copy number variations (CNVs) rather than in single nucleotide variations (SNVs). This review also reveals how little is known about the prognostic significance of epigenetics in NETs. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Feasibility of Home Parenteral Nutrition in Patients with Intestinal Failure Due to Neuroendocrine Tumours: A Systematic Review.
- Author
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Clement, Dominique S. V. M., Brown, Sarah E., Naghibi, Mani, Cooper, Sheldon C., Tesselaar, Margot E. T., van Leerdam, Monique E., Ramage, John K., and Srirajaskanthan, Rajaventhan
- Abstract
Introduction: Maintaining adequate nutritional status can be a challenge for patients with small bowel neuroendocrine tumours (NETs). Surgical resection could result in short bowel syndrome (SBS), whilst without surgical resection there is a considerable risk of ischemia or developing an inoperable malignant bowel obstruction (IMBO). SBS or IMBO are forms of intestinal failure (IF) which might require treatment with home parenteral nutrition (HPN). Limited data exist regarding the use of HPN in patients with small bowel neuroendocrine tumours, and it is not frequently considered as a possible treatment. Methods: A systematic review was performed regarding patients with small bowel NETs and IF to report on overall survival and HPN-related complications and create awareness for this treatment. Results: Five articles regarding patients with small bowel NETs or a subgroup of patients with NETs could be identified, mainly case series with major concerns regarding bias. The studies included 60 patients (range 1–41). The overall survival time varied between 0.5 and 154 months on HPN. However, 58% of patients were alive 1 year after commencing HPN. The reported catheter-related bloodstream infection rate was 0.64–2 per 1000 catheter days. Conclusion: This systematic review demonstrates the feasibility of the use of HPN in patients with NETs and IF in expert centres with a reasonable 1-year survival rate and low complication rate. Further research is necessary to compare patients with NETs and IF with and without HPN and the effect of HPN on their quality of life. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
5. Second Primary Malignancies in Patients with a Neuroendocrine Neoplasm in England.
- Author
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Russell, Beth, White, Benjamin E, Rous, Brian, Wong, Kwok, Bouvier Ellis, Catherine, Srirajaskanthan, Rajaventhan, Van Hemelrijck, Mieke, and Ramage, John K
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SECONDARY primary cancer ,NEUROENDOCRINE tumors ,NOSOLOGY ,SMALL intestine ,STOMACH cancer ,PROSTATE cancer ,THYROID cancer - Abstract
Introduction: Patients with neuroendocrine neoplasms (NENs) may often develop other malignancies. This study aimed to identify the frequency at which these second malignancies occurred in England. Methods: Data were extracted from the National Cancer Registration and Analysis Service (NCRAS) on all patients diagnosed with a NEN at one of eight NEN site groups between 2012 and 2018: appendix, caecum, colon, lung, pancreas, rectum, small intestine, and stomach. WHO International Classification of Disease Edition-10 (ICD-10) codes were used to identify patients who had been diagnosed with an additional non-NEN cancer. Standardized incidence ratios (SIRs) for tumours diagnosed after the index NEN were produced for each non-NEN cancer type by sex and site. Results: A total of 20,579 patients were included in the study. The most commonly occurring non-NEN cancers after NEN diagnosis were the prostate (20%), lung (20%), and breast (15%). Statistically significant SIRs were observed for non-NEN cancer of the lung (SIR = 1.85, 95% CI: 1.55–2.22), colon (SIR = 1.78, 95% CI: 1.40–2.27), prostate (SIR = 1.56, 95% CI: 1.31–1.86), kidney (SIR = 3.53, 95% CI: 2.72–4.59), and thyroid (SIR = 6.31, 95% CI: 4.26–9.33). When stratified by sex, statistically significant SIRs remained for the lung, renal, colon, and thyroid tumours. Additionally, females had a statistically significant SIR for stomach cancer (2.65, 95% CI: 1.26–5.57) and bladder cancer (SIR = 2.61, 95% CI: 1.36–5.02). Conclusion: This study found that patients with a NEN experienced a metachronous tumour of the lung, prostate, kidney, colon, and thyroid at a higher rate than the general population of England. Surveillance and engagement in existing screening programmes are required to enable earlier diagnosis of second non-NEN tumours in these patients. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
6. Sex Differences in Survival from Neuroendocrine Neoplasia in England 2012–2018: A Retrospective, Population-Based Study.
- Author
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White, Benjamin E., Russell, Beth, Remmers, Sebastiaan, Rous, Brian, Chandrakumaran, Kandiah, Wong, Kwok F., Van Hemelrijck, Mieke, Srirajaskanthan, Rajaventhan, and Ramage, John K.
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REPORTING of diseases ,STOMACH tumors ,INTESTINAL tumors ,COLON tumors ,PANCREATIC tumors ,MULTIVARIATE analysis ,RECTUM tumors ,RETROSPECTIVE studies ,LUNG tumors ,SEX distribution ,CANCER patients ,TUMOR classification ,NEUROENDOCRINE tumors ,FACTOR analysis ,OVERALL survival - Abstract
Simple Summary: We conducted a retrospective, population-based study comparing overall survival (OS) between males and females with neuroendocrine neoplasia (NEN). In total, 14,834 cases of NEN recorded in England's National Cancer Registry and Analysis Service (NCRAS)), were analysed. Multivariable analysis, restricted mean survival time and mediation analysis were performed. Females displayed increased survival irrespective of the stage, morphology or level of deprivation, which was statistically significant in NEN of the lung, pancreas, rectum and stomach (p < 0.001). Stage of tumour mediated improved survival in stomach, lung, and pancreatic NEN but not in rectal NEN. Females diagnosed with NEN tend to survive longer than males, and stage at presentation only accounts for part of this effect. Future research in NEN, as well as prognostication and treatment, should consider sex as an important factor. Pre-clinical studies have suggested sex hormone signalling pathways may influence tumorigenesis in neuroendocrine neoplasia (NEN). We conducted a retrospective, population-based study to compare overall survival (OS) between males and females with NEN. A total of 14,834 cases of NEN diagnosed between 2012 and 2018, recorded in England's National Cancer Registry and Analysis Service (NCRAS), were analysed. The primary outcome was OS with 5 years maximum follow-up. Multivariable analysis, restricted mean survival time and mediation analysis were performed. Appendiceal, pulmonary and early-stage NEN were most commonly diagnosed in females; stomach, pancreatic, small intestinal, colonic, rectal and later-stage NEN were more often diagnosed in males. Females displayed increased survival irrespective of the stage, morphology or level of deprivation. On average, they survived 3.62 (95% CI 1.73–5.90) to 10.26 (6.6–14.45) months longer than males; this was statistically significant in NEN of the lung, pancreas, rectum and stomach (p < 0.001). The stage mediated improved survival in stomach, lung, and pancreatic NEN but not in rectal NEN. The reasons underlying these differences are not yet understood. Overall, females diagnosed with NEN tend to survive longer than males, and the stage at presentation only partially explains this. Future research, as well as prognostication and treatment, should consider sex as an important factor. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
7. Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with Lu-177-Dotatate : an analysis of the NETTER-1 study
- Author
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Strosberg, Jonathan, Kunz, Pamela L., Hendifar, Andrew, Yao, James, Bushnell, David, Kulke, Matthew H., Baum, Richard P., Caplin, Martyn, Ruszniewski, Philippe, Delpassand, Ebrahim, Hobday, Timothy, Verslype, Chris, Benson, Al, Srirajaskanthan, Rajaventhan, Pavel, Marianne, Mora Salvador, Jaume, Berlin, Jordan, Grande, Enrique, Reed, Nicholas, Seregni, Ettore, Paganelli, Giovanni, Severi, Stefano, Morse, Michael, Metz, David C., Ansquer, Catherine, Courbon, Frédéric, Al-Nahhas, Adil, Baudin, Eric, Giammarile, Francesco, Taïeb, David, Mittra, Erik, Wolin, Edward, O’Dorisio, Thomas M., Lebtahi, Rachida, Deroose, Christophe M., Grana, Chiara M., Bodei, Lisa, Öberg, Kjell, Polack, Berna Degirmenci, He, Beilei, Mariani, Maurizio F., Gericke, Germo, Santoro, Paola, Erion, Jack L., Ravasi, Laura, Krenning, Eric, Netter-1 Study Group, Service de médecine nucléaire [Marseille], Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), and Radiology & Nuclear Medicine
- Subjects
Target lesion ,177Lu-Dotatate ,NETTER-1 study group ,Phases of clinical research ,Octreotide ,Lu-177-Dotatate ,Liver tumour burden ,NETTER-1 ,Neuroendocrine tumour ,Gastroenterology ,0302 clinical medicine ,Medicine ,ComputingMilieux_MISCELLANEOUS ,Cancer ,Liver Neoplasms ,Hazard ratio ,General Medicine ,Other Physical Sciences ,Nuclear Medicine & Medical Imaging ,Neuroendocrine Tumors ,Treatment Outcome ,030220 oncology & carcinogenesis ,Original Article ,medicine.symptom ,Liver cancer ,medicine.drug ,Radiology, Nuclear Medicine and Medical Imaging ,medicine.medical_specialty ,Liver tumor ,Clinical Trials and Supportive Activities ,Clinical Sciences ,030209 endocrinology & metabolism ,NO ,Càncer de fetge ,Lesion ,03 medical and health sciences ,Clinical Research ,Internal medicine ,Organometallic Compounds ,Humans ,Radiology, Nuclear Medicine and imaging ,Progression-free survival ,Tumors ,Cancer och onkologi ,business.industry ,Alkaline Phosphatase ,medicine.disease ,Cancer and Oncology ,Liver function ,Radiologi och bildbehandling ,Digestive Diseases ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Purpose To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate. Methods In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression. Results Significantly prolonged median PFS occurred with 177Lu-Dotatate versus octreotide LAR 60 mg in patients with low ( 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the 177Lu-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden. Conclusions 177Lu-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. Clinicaltrials.gov: NCT01578239, EudraCT: 2011-005049-11
- Published
- 2020
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