Presentation by Dr Lim Hwee Yong, Medical Oncologist, National Cancer Centre Singapore, at a NET cancer awareness seminar in Singapore on 20 November 2010.
An overview of Clinical Trials for Metastatic HER2-positive Breast Cancer by Dr. Ian Krop, MD, PhD, Chief and Clinical Research Director, Breast Oncology Center at Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute
Presentation by Dr Lim Hwee Yong, Medical Oncologist, National Cancer Centre Singapore, at a NET cancer awareness seminar in Singapore on 20 November 2010.
An overview of Clinical Trials for Metastatic HER2-positive Breast Cancer by Dr. Ian Krop, MD, PhD, Chief and Clinical Research Director, Breast Oncology Center at Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute
Optimizing Therapeutic Strategies in Castration-Resistant Prostate Canceri3 Health
This activity will discuss emerging efficacy and safety data on novel therapies for nmCRPC and mCRPC, strategies to manage adverse events, and the role of imaging studies and PSA testing in evaluating treatment response.
Report Back from San Antonio Breast Cancer Symposium (SABCS 2022)bkling
Curious about the latest developments in Early-Stage Breast Cancer and Metastatic Breast Cancer Research? Join us as Dr. Anne Blaes, the Division Director of Hematology/Oncology/Transplantation and Professor in Hematology/Oncology at the University of Minnesota, breaks down the most recent developments released at the annual San Antonio Breast Cancer Symposium regarding early-stage and metastatic breast cancer research.
Randomized comparison of adjuvant aromatase inhibitor exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor positive (HR+) early breast cancer (BC):
Lung cancer is a major cause of cancer deaths with approximately 80% of cases accounting to nonsmall cell lung cancer (NSCLC) . In NSCLC target therapy, epidermal growth factor receptor (EGFR) is a promising candidate.
Optimizing Therapeutic Strategies in Castration-Resistant Prostate Canceri3 Health
This activity will discuss emerging efficacy and safety data on novel therapies for nmCRPC and mCRPC, strategies to manage adverse events, and the role of imaging studies and PSA testing in evaluating treatment response.
Report Back from San Antonio Breast Cancer Symposium (SABCS 2022)bkling
Curious about the latest developments in Early-Stage Breast Cancer and Metastatic Breast Cancer Research? Join us as Dr. Anne Blaes, the Division Director of Hematology/Oncology/Transplantation and Professor in Hematology/Oncology at the University of Minnesota, breaks down the most recent developments released at the annual San Antonio Breast Cancer Symposium regarding early-stage and metastatic breast cancer research.
Randomized comparison of adjuvant aromatase inhibitor exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor positive (HR+) early breast cancer (BC):
Lung cancer is a major cause of cancer deaths with approximately 80% of cases accounting to nonsmall cell lung cancer (NSCLC) . In NSCLC target therapy, epidermal growth factor receptor (EGFR) is a promising candidate.
NIH Presentation Nov 2016 Neuroendocrine Tumor Clinical TrialsCACSNETS
NIH/NCI presentation provides an overview of and NIH clinical trials. Briefing covers: 1) Overview of GI and pancreatic Neuroendocrine Tumors (NETs) /Carcinoid Cancer;
2) Treatment options for patients with advanced GI and pancreatic NETs; 3) Clinical trials for/in patients with NETs
Sites of the highest risk are the duodenum, for adenocarcinomas, and the ileum, for carcinoids and lymphomas.
In industrialized countries, small bowel cancers are predominantly adenocarcinomas;
In developing countries, lymphomas are much more common.
The incidence of small bowel cancer rises with age and has generally been higher among males than among females.
The risk factors for small bowel cancer include
Dietary factor
Cigarette smoking,
Alcohol intake,
Medical conditions -Crohn's disease, familial adenomatous polyposis, cholecystectomy, peptic ulcer disease, and cystic fibrosis.
The protective factors may include rapid cell turnover, a general absence of bacteria, an alkaline environment, and low levels of activating enzymes of precarcinogens.
Dr. Manuel Hidalgo - Simposio Internacional ' Terapias oncológicas avanzadas'Fundación Ramón Areces
Los días 15 y 16 de octubre de 2014, la Fundación Ramón Areces y la Real Academia Nacional de Farmacia, en colaboración con la Fundación de la Innovación Bankinter, reunieron en Madrid a algunos de los mayores expertos mundiales en nuevas terapias contra el cáncer. El Simposio Internacional, coordinado por la profesora y académica María José Alonso, analizó el momento actual de la lucha contra esta enfermedad. También fue un punto de encuentro para científicos de los más innovadores institutos de investigación en oncología, quienes debatieron sobre tres grandes temas: la Medicina Personalizada contra el cáncer, los nanomedicamentos en la terapia del cáncer y las terapias basadas en la inmunomodulación.
Describes the emerging resistance of epithelial cancer of the ovary to current therapies and the role of PARP inhibitors in the management in view of the recent drug approvals.
Management of MSI High Solid Tumors and the impact of adding Immunotherapy upon improving survival outcome and response rate. Colorectal and Non Colorectal tumors.
Prostate cancer the androgenic fortified dogmaMohamed Abdulla
It describes the androgenic nature of prostate cancer and the androgenic axis should be tackled in all phases of prostate cancer. Also a special emphasis on recent data on management of metastatic hormone sensitive prostate cancer.
Expanding treatment platform in m crc bayer - asyut 2018Mohamed Abdulla
Describes the different therapeutic approach to patients with metastatic colorectal cancer in the 3rd subsequent treatment line with especial emphasis on the role of regorafenib and how to manipulate the adverse events while not compromise the outcome.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
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Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journey
Neuroendocrine tumors in 2015
1. ROLE OF TARGETED THERAPY
IN NEUROENDOCRINE TUMORS
Mohamed Abdulla M.D.
Prof. of Clinical Oncology
Kasr Al-Aini School of Medicine
Cairo University
Target Therapy: Future Directions
Helnan Palestine Hotel
Thursday, 30/04/2015
5. Incidence of NETs Is Increasing*
5 5
SEER = Surveillance, Epidemiology, and End Results (for malignant NETs)
*Approximate 5-fold increase between 1975 and 2004
Approximate 7-fold increase also evident in Norwegian registry
IncidencePer100,000
1.40
Year
NET Site
1.20
1.00
0.80
0.60
0.40
0.20
0
Lung
Colon
Small intestine
Rectum
Pancreas
Yao JC, Hassan M, Phan A, et al. J Clin Oncol. 2008;26:3063-3072.
6. Colon Neuroendocrine Stomach
29-year limited duration prevalence analyses based on SEER
Pancreas Esophagus Hepatobiliary
0
100
1,100
NET Prevalence in the US, 2004
1,200
Median survival (1988 –
2004)103,312
cases
(35/100,000)
No.ofcases
(thousands)
Adapted from: Yao JC, et al. J Clin Oncol. 2008;26(18):3063-3072.
NETs Are the 2nd-Most Prevalent
Gastrointestinal Tumor:
• Localized
• Regional
• Distant
203 months
114 months
39 months
10. Key Issues in The Management:
1. How do we define the disease?
Nomenclature, Classification & Pathology.
2. Who needs treatment and when?
Patient Selection.
3. Which treatment and in what sequence?
Treatments.
4. What is the role of combined biologics,
somatostatin analogues, cytotoxics and
biomarkers?
Unanswered Questions.
11. 1.How do we define the disease?
Nomenclature, Classification and
Pathology
12. Evolution of Terminology & Classification:
Historic Evolution:
1907 1963 1970 1980 1995
Carcinoid
Williams &
Sandler
Soga &
Tazawa
Histologic
WHO
Granular
Stain
Techniques
Capella
Size &
Invasion
• Benign.
• Benign or Low
Grade Malignant.
• Low Grade
Malignant.
• High Grade
Malignant.
No Prognostic or Predictive
Validation
13. Evolution of Terminology & Classification:
Histopathologic Differentiation:
Well
Differentiated
Poorly
Differentiated
14. Evolution of Terminology & Classification:
AJCC Criteria of Grading:
Grade Mitotic
Count (per
10 HPF)
Ki 67
Index (%)
G1 < 2 < 2
G2 2 – 20 3 – 20
G3 > 20 > 20
AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer New York, Inc.
15. Evolution of Terminology & Classification:
Correlation of Tumor Grade With Survival:
1. Rindi G, Klöppel G, Alhman H, et al. Virchows Arch. 2006;449:395-401. 2. Rindi G, Klöppel G, Couvelard A, et al.
Virchows Arch. 2007;451:757-762. 3. Pape UF, Jann H, Müller-Nordhorn J, et al. Cancer. 2008;113:256-265.
0 50 100 150 200 250
Survival Time (mo)
0.0
0.2
0.4
0.6
0.8
1.0
CumulativeSurvival
G1
G2
G3
G1 vs G2
G1 vs G3
G2 vs G3
P=0.040
P<0.001
P<0.001
N=193
16. Scarpa A, et al. Mod Pathol. 2010;23(6):824-
833.
Prognostic Influence of Ki67-
Labelling
< 2% 15% 75%
Pape UF, et al. Endocr Relat
Cancer. 2008;15(4):1083-1097.
Ekeblad S, et al. Clin Cancer Res. 2008;14(23):7798-
7803. Vilar E, et al. Endocr Relat Cancer. 2007;14(2):221-
232.
17. Evolution of Terminology & Classification:
Correlation of TNM Staging With Survival:
17 17
La Rosa S, Klersy C, Uccella S, et al. Hum Pathol.
2009;40:30-40.
Patients With Well-Differentiated Pancreatic NET
Stage I
P<0.001
ProportionAlive
Stage II
Stage III
Stage IV
I (n = 44)
II (n = 44)
III (n = 34)
IV (n = 33)
Time (mo)
0.00
0.25
0.50
0.75
1.00
0 48 96 144 192 240
18. Evolution of Terminology & Classification:
Metastatic Disease Is Common at Presentation:
Localized Metastatic
50%
27%
23%
Distant metastases
Regional spread
Data from an analysis of 28,515 cases of NET identified in the SEER registries
Yao JC, Hassan M, Phan A, et al. J Clin Oncol. 2008;26:3063-3072.
*These data are of the cases in which stage was reported.
20% of cases did not provide disease stage information
19. Evolution of Terminology & Classification:
NETs Are Often Diagnosed Late:
Vinik AI, Silva MP, Woltering EA, et al. Pancreas. 2009;38:876-889.
1 2 3 4 5 6 7 8 9
Time (yr)
Primary tumour growth
Metastases
Flushing
Diarrhea
Death
Vague abdominal symptoms
Estimated time to diagnosis: 5 to 7 yr
*
*
*Symptoms of carcinoid syndrome
21. Pan-neuroendocrine markers
Cytosolic NSE, PGP 9.5
Related to secretory
granules
Chromogranin
Related to synaptic vesicles Synaptophysin, VMAT
Intermediate filaments NF, CK HMW
Adhesion molecules N-CAM
Immunohistochemical NE markers:
22. Chromogranin A*
(in 70%-90% increased in metast. NET)
Pancreatic Polypeptide, PP
(in 40%-55 % elevated);
a-HCG, β-HCG
(in ~ 30% elevated)
Neuron specific enolase (NSE)
(in ~33% elevated)
*The height of Chromogranin A level correlates with tumor load,
an increase over time indicates tumor progression
Circulating Tumor Markers:
23. CgA correlates with hepatic tumor load
Heigher CgA levels indicate lower survival
Arnold R, et al. Clin Gastroenterol Hepatol. 2008;6(7):820-827
Prognostic Value of CgA:
24. HR = 0.25
95% CI: 0.13-0.51
P = .00004
Median PFS
Early response = 13.3 mos.
No early response = 7.5 mos.
0 3 6 9 12 15 18 21 24 0 3 6 9 12 15 18 21 24
HR = 0.25
95% CI: 0.10-0.58
P = .00062
CgA NSE Median PFS
Early response = 8.6 mos.
No early response = 2.9 mos.
PFS(%)
0
20
40
60
80
100
0
20
40
60
80
100
Time Since Study Start, months Time Since Study Start, months
Pts at Risk Pts at Risk
Resp. 33 29 26 19 12 5 3 2 0 Resp. 28 23 16 9 6 3 1 0 0
Nonresp 38 26 12 5 1 1 0 0 0 Nonresp. 11 5 2 0 0 0 0 0 0
Yao JC, et al. J Clin Oncol. 2010;28(1):69-76.
RADIANT-1 (Stratum I)
Predictive Value of Biomarkers:
PFS by Early CgA and NSE Responses:
25. Modlin IM, et al. Ann Surg Oncol. 2010;17(9):2427-2443.
PPI
Chronic Atrophic
Gastritis
PPI
H2RAs
Small cell lung cancer
Prostate cancer
Breast cancer
Ovary Cancer
Chronic atrophic gastritis
Pancreatitis
Inflammatory bowel disease
Irritable bowel syndrome
Liver cirrhosis
Chronic hepatitis
Colon cancer
HCC
Pancreatic adenocarcinoma
Pheochromocytoma
Hyperparathyroidism
Pituituary tumors
Medullary thyroid carcinoma
Hyperthyroidism
CgA
ENDOCRINE
DISEASE
GASTRO-
INTESTINAL
DISORDERS
NON-GI
CANCER
Arterial hypertension
Cardiac insufficiency
Acute coronary syndrome
Giant cell arteritis
CARDIOVASCULAR
DISEASE
Systemic rheumatoid arthritis
Systemic inflammatory response syndrome
Chronic bronchitis
Airway obstruction in smokers
INFLAMMATORY
DISEASES
Renal Insufficiency
RENAL DISORDERS
DRUGS
Causes of Chromogranin A Elevation:
28. Therapy of NETs
Three principles
• Control of hormonal
symptoms
• Control of tumor
growth
• Improvement of
survival?
Symptomatic
therapy
Surgical
therapy
Antiproliferative
therapy
• Cure
• Debulking
• Treatment /
Prevention of
complications
29. Somatostatin Receptors (SSTR) Are
Expressed by the Majority of NETs
• SSTR2 is most prevalent in GEP-NETs and induces
inhibitory effects on hormone secretion and proliferation
in NETs
• Somatostatin is effective in controlling NET-related
hormonal symptoms
• Clinical use of somatostatin is limited by its short half life
Basu B, et al. Endocr Relat Cancer. 2010;17(1):R75-R90. Modlin IM, et al. Aliment Pharmacol Ther.
2010;31(2):169-188. Hofland LJ. J Endocrinol Invest. 2003;26(8 Suppl):8-13. Ferrante E, et al. Endocr Relat
Cancer. 2006;13(3):955-962.
Prevalence on NET type: SSTR1 SSTR2 SSTR3 SSTR4 SSTR5
Pancreas 68% 95% 46% 93% 57%
Midgut 80% 86% 65% 35% 75%
Inhibitory effect:
Hormone secretion + + +
Proliferation + + + +
Induction of apoptosis + +
30. • Octreotide and lanreotide show high affinity for the
SSTR2 and are approved for antisecretory treatment in
NETs
LAR, long lasting release
Susini C, et al. Ann Oncol. 2006;17(12):1733-
1742.
Octreotide LAR
(10-30 mg / 28 days im)
Lanreotide
(60-120 mg / 28 days sc)
Octreotide
(2-3 x 50-500 ug sc / d)
Biotherapy of Functional Active NETs
With Somatostatin Analogs (SSA)
S
S
a
l
a
g
l
y
ly asn
s
cys p
h
e
p
h
e
p
h
e tr
p
l
y
s
t
h
r
p
h
e
t
h
r
s
e
r
cys
D-phe c
y
s
phe
l
y
s
c th
y r
s
Octreotide
acetate
D-trp
Thr
-
ol
D-phe c
l
y
s
v
al
c
y
y
s
S
ty
r
s
Lanreotid
e
D-trp
Thr
-
NH2
S
Somatostatin
S
S
31. Phase III Study of Octreotide LAR:
Patients:
• Well-differentiated
midgut NET
• Treatment-naïve
• Locally inoperable
or metastasized
N = 85
Octreotide LAR
30 mg im/28 days
Placebo
im/28 days
Primary endpoint:
• Median time to tumour progression
Rinke A, Müller HH, Schade-Brittinger C, et al. J Clin Oncol. 2009;27:4656-4663.
1:1
R
A
N
D
O
M
I
Z
E
Secondary endpoints:
•Objective tumour response rate
• Symptom control
• Overall survival
Treatment
until CT/MRI
documented
tumour
progression
or death
Randomized, Double-blind, Placebo-controlled Study
32. Octreotide LAR 30 mg
Significantly Prolongs TTP:
HR = hazard ratio. PROMID = Placebo-controlled prospective Randomized study on the antiproliferative efficacy of Octreotide LAR in patients
with metastatic neuroendocrine MIDgut tumours; TTP = time to progression
Rinke A, Müller HH, Schade-Brittinger C, et al. J Clin Oncol. 2009;27:4656-4663.
Octreotide LAR vs placebo
HR=0.34 P=0.000072
[95% CI: 0.20–0.59]
Based on conservative ITT analysis
ProportionWithout
Progression
1.0
.75
.50
.25
0
0 6 12 18 24 30 36 42
Time (mo)
48 54 60 66 72 78
Octreotide LAR (n = 42)
Median 14.3 mo
Placebo (n = 43)
Median 6.0 mo
33. Octreotide LAR 30 mg Extends TTP in Patients With
Functioning and Nonfunctioning Tumours:
0
0.25
0.5
0.75
1
0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90
0
0.25
0.5
0.75
1
0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90
Based on the per-protocol analysis
P=0.0008; HR=0.25 (95% CI: 0.10–0.59)
ProportionWithoutProgression
P=0.0007; HR=0.23 (95% CI: 0.09–0.57)
ProportionWithoutProgression
Patients with nonfunctioning tumours Patients with functioning tumours
Time (mo)Time (mo)
Octreotide LAR 30 mg: 17 pts/11 events
Median TTP 14.26 mo
Placebo: 16 pts/14 events
Median TTP 5.45 mo
Octreotide LAR 30 mg: 25 pts/9 events
Median TTP 28.8 mo
Placebo: 27 pts/24 events
Median TTP 5.91 mo
1. Arnold R, Müller H, Schade-Brittinger C, et al. J Clin Oncol. 2009;27(suppl):15s. Abstr 4508.
2. Rinke A, Müller HH, Schade-Brittinger C, et al. J Clin Oncol. 2009;27:4656-4663.
35. Lanreotide Acetate in NET:
• Patient Characteristics: Clarinet Trial:
• Well to Moderately differentiated.
• Ki 67 < 10%
• Pancreas, mid-gut, hind-gut, or Unknown origin.
N Engl J Med 2014;371:224-33.
36. The SYM-NET StudyDESIGNASSESSMENTS
A non-interventional cross sectional study to assess SYMptom
control in neuroendocrine tumors (NET)
Non-interventional, cross-sectional study
273 patients suffering from NET, already treated with lanreotide for at least 3
months and with history of diarrhea due to carcinoid syndrome were
enrolled
Subject questionnaires
Investigator review
of medical record
Likert scales
• Patient satisfaction
• Symptom severity
• Perception change
diarrhea
• Feelings about conse-
quences on daily life
QoL
• EORTC C30
• EORTC GI-
NET21
Demography
Medical
history
Treatment with
lanreotide
Diarrhea
Ruszniewski PB, et al. J Clin Oncol. 2014.32(5s): Abstract 411ˆ
characteristics
• At Tt initiation
• Day of visit
Other clinical
data
• At Tt initiation
• Day of visit
Qol = quality of life
37. SYM-NET Study – Results and Conclusion
Ruszniewski PB, et al. J Clin Oncol. 2014.32(5s): Abstract
411ˆ
• An improvement was observed for the majority
of patients in all symptoms
– 76 % patient satisfaction with diarrhea control (primary
objective)
– 73 % patient satisfaction with flushing control
– QoL questionnaires showed a high level of activity
capacity and low symptoms score
• Patient-reported "subjective" information was
consistent with investigator’s observation
• Confirms in real life setting the satisfactory effect
of lanreotide on symptoms of hormonal excess in
GEP- NETs
38. Chemotherapy for Well-Differentiated
NETs of the Pancreas and
Duodenum:
Author
Turner NC, et al. Br J Cancer. 2010;102(7) 1106-1112.
Chemotherapy
Pt
(n)
RR mOS
(%) (months)
Cheng (1999)1 & Mc Collum (2003)2 STZ + DOX 16 & 16 8 -----
Eriksson (1990)3
Dealunoit (2004)4
Rivera et al. (1998)5
Kouvaraki et al. (2004)6
Turner et al. (2010)7
STZ + DOX
STZ + DOX
STZ + 5-FU + DOX
STZ + 5-FU + DOX
STZ + 5-FU + cispl.
84
45
12
84
47
36 ------
36 24
55 21
39 37
38§ 31.5
1. Cheng PN, et al. Cancer. 1999;86(6):944-948. 2. McCollum AD, et al. Am J Clin Oncol. 2004;27(5):485-488.
3. Eriksson B, et al. J Intern Med. 1990;228(2):103-113. 4. Delaunoit T, et al. Eur J Cancer. 2004;40(4):515-
520. 5. Rivera E, et al. Am J Clin Oncol. 1998;21(1):36-38. 6. Kouvaraki MA, et al. J Clin Oncol.
2004;22(23):4762-4771. 7.
42. Neuroendocrinal Tumors:
Molecular Events & Therapeutic Implications:
2. mTOR Inhibitor:
Mammalian Target of Rapamycin
Cellular
Growth
Protein
Synthesis
Autophagy
Resistance to
Apoptosis
++
Proliferation
Altered
Metabolism
43. RADIANT-3
PFS by Investigator Review:
• P value obtained from stratified 1-sided log-rank test
• Hazard ratio is obtained from stratified unadjusted Cox model
%Event-free
0 2 4 6 8 10
No. of patients still at risk
Kaplan-Meier median PFS
Everolimus:
Placebo:
11.0 mo
4.6 mo
Hazard ratio = 0.35; 95% CI 0.27–0.45
P value: <.0001
PFS rate (18 mos.)
Everolimus 34.2%
Placebo 8.9%
Yao JC, et al. N Engl J Med. 2011;364(6):514-
12 14 16 18
Time (mo)
100
80
Censoring times Everolimus
(n/N = 109/207) Placebo
(n/N = 165/203)
60
40
20
0
20 22 24 26 28 30
44. RADIANT-3: Treatment-Related G3/4
AE:
Yao JC, et al. N Engl J Med. 2011;364(6):514-
523.
*Related toxicities grouped for
calculation
Occurring in >10%
Everolimus n = 204
All Grades (%) Grade 3/4 (%)
Placebo n = 203
All Grades (%) Grade 3/4 (%)
Stomatitis* 64 7 17 0
Rash 49 <1 10 0
Diarrhea 34 3 10 0
Fatigue 31 2 14 <1
Nausea 20 2 18 0
Infections* 23 3 6 1
Peripheral edema 20 <1 3 0
Decreased appetite 20 0 7 1
45. RADIANT-2 Study Design:
Everolimus 10 mg/day +
Octreotide LAR 30 mg/28 days
n = 216
Placebo +
Octreotide LAR 30 mg/28 days
n = 213
Treatment
until disease
progression
R
A
N
D
O
M
I
Z
E
1:1
Multiphasic CT or MRI performed every 12 wk
Crossover
Primary endpoint:
• PFS (RECIST)
Secondary endpoints:
• Tumour response, OS, biomarkers, safety, PK
Enrollment January 2007–May 2008
Phase III, Double-blind, Placebo-controlled Trial
Pavel M, Hainsworth J, Baudin E, et al. Presented at: 35th ESMO Congress; October 8-12, 2010; Milan, Italy. Abstr LBA8.
Patients with advanced NET
(N=429)
• Advanced low- or intermediate-
grade NET
• Radiologic progression <12
months
• History of secretory symptoms
(flushing, diarrhea)
• Prior antitumour therapy allowed
• WHO PS ≤2
46. PFS by Central Review:*
Time (mo)
No. of patients still at risk
E + O
P + O
216
213
202
202
167
155
129
117
120
106
102
84
81
72
69
65
63
57
56
50
50
42
42
35
33
24
22
18
17
11
11
9
4
3
1
1
1
0
0
0
* Independent adjudicated central review committee
• P-value is obtained from 1-sided log-rank test
• HR is obtained from unadjusted Cox model
E + O = everolimus + octreotide LAR
P + O = placebo + octreotide LAR
0
20
40
60
80
100
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38
PercentageEvent-free
Kaplan-Meier median PFS
Everolimus + octreotide LAR: 16.4 mo
Placebo + octreotide LAR: 11.3 mo
HR = 0.77; 95% CI (0.59–1.00)
P=0.026
Total events = 223
Censoring times
E + O (n/N = 103/216)
P + O (n/N = 120/213)
Pavel M, Hainsworth J, Baudin E, et al. Presented at: 35th ESMO Congress; October 8-12, 2010; Milan, Italy. Abstr LBA8.
47. Subgroup PFS Analysis:
*Independent adjudicated central review
HR = everolimus + octreotide/placebo + octreotide
Unstratified Cox model was used to obtain HR
E + O = everolimus + octreotide LAR
P + O = placebo + octreotide LAR
Subgroups (N)
Central review *(429)
Local investigator review (429)
Age group
<65 yr (286)
≥65 yr (143)
Gender
Male (221)
Female (208)
WHO Performance Status
WHO = 0 (251)
WHO > 0 (176)
Tumour histology grade
Well-diff. (341)
Moderately diff. (68)
Primary tumour site
Small intestine (224)
Lung (44)
Colon (28)
Other (132)
Prior long-acting SSA
Yes (339)
No (90)
Prior chemotherapy
Yes (130)
No (299)
HR
Median PFS
(mo)
E + O P + O
0.77 16.4 11.3
0.78 12.0 8.6
0.78 19.2 13.0
0.75 13.9 11.0
0.85 13.7 13.0
0.73 17.1 11.1
0.67 21.8 13.9
0.81 13.6 8.3
0.74 18.3 13.0
0.82 13.7 7.5
0.77 18.6 14.0
0.72 13.6 5.6
0.39 29.9 13.0
0.77 14.2 11.0
0.81 14.3 11.1
0.63 25.2 13.6
0.70 13.9 8.7
0.78 19.2 12.0
Hazard Ratio
Favors E + O Favors P + O
0 10.4 0.8 1.4
Pavel M, Hainsworth J, Baudin E, et al. Presented at: 35th ESMO Congress; October 8-12, 2010; Milan, Italy. Abstr LBA8.
48. 5050
Sunitinib vs Placebo in Advanced pNET:
• Phase III randomized, placebo-controlled, double-blind trial
• Trial stopped after early unplanned analysis showed efficacy and safety
benefit
Primary Endpoint: PFS
Secondary Endpoints: OS, ORR, TTR, duration of response, safety, and patient-reported
outcomes
Patients with
advanced pNET,
N = 171/340
patients enrolled
Sunitinib 37.5 mg/day orally
Continuous daily dosing*
n = 86
Placebo*
n = 85
*With best supportive care
Somatostatin analogues were permitted
Raymond E, Dahan L, Raoul J-L, et al. N Engl J Med. 2011;364:501-513.
1:1
R
A
N
D
O
M
I
Z
E
49. 51 51
0.8
0.6
0.4
0.2
0
1.0
ProportionofPatients
5 10 15 20 250
Sunitinib
39 19 4 0 086Sunitinib
28 7 2 1 085Placebo
Number at risk
Time (mo)
Placebo
Kaplan-Meier median PFS
Sunitinib: 11.4 mo
Placebo: 5.5 mo
HR = 0.42 (95% CI, 0.26–0.66)
P<0.001
Progression-free Survival:*
Raymond E, Dahan L, Raoul J-L, et al. N Engl J Med. 2011;364:501-513.
* Local review
50. 1.0
PRRT
Objective
response: Stable
disease: Median
survival:
34%
5%
94.6
months
Open phase II study, 1,109 patients
with progressive NET (within 12
months), 2,472 cycles 90Y-DOTA-
TOC-therapy, median follow up 23
months
• Objective response rates 30% - 40%
• Survival benefit in responders likely
• Limitations: safety concerns (renal, bone marrow
toxicity), limited availability, lacking randomized studies
0 2 4 6 8 10
12
Time Since Start of Treatment,
years
14
0.2
0.4
0.6
0.8
OverallSurvival,probability
Imhof A, et al. J Clin Oncol. 2011;29(17):2416-
1423.
No. of
patient
s
No. of
deaths
Median
survival
Hazard
ratio
P
Disease
control
671 280 3.8 years 0.41 vs
progress
<.001
Progress 438 211 1.4 years
51.
52.
53. Final Take Home Message:
• NET not rare.
• Surgery is the Cornerstone in Curative
Management.
• Serum Biomarkers Are Still There to Share.
• Tissue Markers Should be more Highlighted.
• Molecular Targeted Therapies are The Hope for
Tomorrow.