This document summarizes a tumor board discussion of a case involving a 21-year-old patient presenting with loose stools and abdominal pain for 2 months. Key details include KRAS mutation testing of the patient's tumor sample, which showed no mutation. The discussion covers epidemiology of early-onset colorectal cancer in India, treatment options including chemotherapy and targeted therapies, and factors influencing first-line treatment decisions for metastatic colorectal cancer such as biomarker status and primary tumor location.
Artery first approach For Pancreatic Head tumours by Dr Harsh Shah (www.gastr...Dr Harsh Shah
Artery first approach to Pancreatic head tumour. There are various approaches as described in this presentation. Pros & Cons of all approaches are discussed.
TUMOUR MARKERS- FOR SURGEONS
#surgicaleducator #tumourmarkers #usmle #babysurgeon #surgicaltutor
• Dear Viewers,
• Greetings from “Surgical Educator”
• Today I have uploaded a video on Tumour Markers for Surgeons- a didactic lecture.
• I have discussed the definition, applications, clinical use and the normal values of many Tumour Markers useful to Surgons.
• I hope the video will be very useful and you will enjoy it.
• You can watch all my surgical teaching videos in the following link:
• youtube.com/c/surgicaleducator
• Thank you for watching the video.
Artery first approach For Pancreatic Head tumours by Dr Harsh Shah (www.gastr...Dr Harsh Shah
Artery first approach to Pancreatic head tumour. There are various approaches as described in this presentation. Pros & Cons of all approaches are discussed.
TUMOUR MARKERS- FOR SURGEONS
#surgicaleducator #tumourmarkers #usmle #babysurgeon #surgicaltutor
• Dear Viewers,
• Greetings from “Surgical Educator”
• Today I have uploaded a video on Tumour Markers for Surgeons- a didactic lecture.
• I have discussed the definition, applications, clinical use and the normal values of many Tumour Markers useful to Surgons.
• I hope the video will be very useful and you will enjoy it.
• You can watch all my surgical teaching videos in the following link:
• youtube.com/c/surgicaleducator
• Thank you for watching the video.
This study was performed to analyze the efficacy and safety of con-current radiotherapy and weekly paclitaxel in the treatment of carcinoma of uterine cervix. Hundred patients with locally advanced (stages IIB to IVA according to FIGO classification) carcinoma of uterine cervix were enrolled, radiotherapy was conventionally administered: 50.4 Gy/28 fractions by external beam (whole pelvis) followed by HDR-Intracavitary brachytherapy, 4 fractions of 7 Gy each. Paclitaxel was administered on weekly basis at dose of 40 mg ∕m2 during entire course of external beam radiotherapy. Treatment response was evaluated three months after the end of radiotherapy by means of clinical examination and ultrasonography. Complete Regression (CR) in 83%, partial response (PR) 14% and progressive disease 3%. At 26 months of median follow up 73 patients alive, 58 patients are disease free. The results of this study suggest that concurrent chemo radiotherapy is feasible in treatment of carcinoma cervix with acceptable and manageable toxicity and paclitaxel act as radio sensitizer in locally advanced cervical cancer.
Journal Club: Prophylactic Thyroidectomy in Multiple Endocrine Neoplasia 2 Dr. Aryan (Anish Dhakal)
The study aims to analyze the long-term results of a large cohort of MEN2 patients with the C634Y mutation who had undergone prophylactic thyroidectomy in a tertiary referral hospital, and to analyze the results in terms of age and calcitonin levels.
Laparoscopic Low Anterior Resection for Cancer : “Pursued or just Permitted?”...Dimitris P. Korkolis
Potential Advantages of Lap TME
- Less blood loss
- Faster recovery
- Earlier return of gut function
- Lower morbidity and mortality
- Magnified view allows precise dissection (pelvic autonomics)
- Earlier hospital discharge
Presentation by Scott Oliver, MD. Presented at the 2018 Eyes on a Cure: Patient & Caregiver Symposium, hosted by the Melanoma Research Foundation's CURE OM initiative.
Scans and Ovarian Cancer: Everything You Want to Knowbkling
When you’re diagnosed with ovarian cancer, scans become an inevitable part of life. But what are the differences between the imaging tests? When should which scans be used? What about the pros and cons of each test? Join Dr. Kevin Holcomb, Vice-Chair of Gynecology and member of the Division of Gynecologic Oncology at Weill Cornell Medicine, and Dr. Elisabeth O’Dwyer, Instructor in Radiology at Weill Cornell Medicine and Assistant Attending Radiologist at NewYork-Presbyterian Hospital-Weill Cornell Campus, as they help make sense of it all.
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
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
9. EPIDEMIOLOGY
- Incidence of colorectal cancer in India is 3.6 – 4.1 per
100,000
- Left sided tumors are more common
-Around 2/3
- ~ 25% of patients are < 40 years of age
- More proximal tumors
10. EPIDEMIOLOGY
- Incidence of CRC in India expected to rise by 80% by
2035
- 114,000 new cases with mortality ~ 87,000
- 25% of patients present with metastases
- 35% develop metastases after primary therapy
- k-ras mutation is around 40 %
-Similar to world-wide data
11. PREDICTION IS MORE WORRISOME
Annual percentage change-based predicted incidence rates of rectosigmoid and
rectal cancers by age compared with incidence rate in 2010
Bailey CE, et al. JAMA Surgery. 2015;150:17-22.
12. CRC > 55
INCIDENCE AND MORTALITY TRENDS
~1990s
2011
CRC 50 - 55
EAO CRC
Per
100,000
years
13.
14.
15.
16.
17.
18.
19.
20.
21. CRC : HCG BANGALORE
Veldore VH, Rao MR, Prabhudesai SA, Tejaswi R, Kakara S, Pattanayak S, et al. Prevalence of KRAS mutations in metastatic
colorectal cancer: A retrospective observational study from India. Indian J Cancer 2014;51:531-7.
Prevalence of KRAS mutation
(42.8%) in India is at par with world
literature that varies from 30% to
60%.
24. MADURAI 625009
TAMIL NADU INDIA
0452-2510000 8248883595
CLIENT CODE : C000051601
CLIENT'S NAME AND ADDRESS :
VELAMMAL MEDICAL COLLEGE HOSPITAL & RESEARCH INSTITUTE
VELLAMMAL VILLAGE, MADURAI-TUTICORIAN RING ROAF, ANUPPANADI,
DIAGNOSTIC REPORT
SRL LIMITED
PRIME SQUARE BUILDING,PLOT NO 1,GAIWADI INDUSTRIAL
ESTATE,S.V. ROAD,GOREGAON (W)
MUMBAI, 400062
MAHARASHTRA, INDIA
Tel : 1-800-222-000, Fax : 022 - 67801212
CIN - U74899PB1995PLC045956
Email : connect@srl.in
PATIENT ID :PATIENT NAME : AJITH KUMAR
ACCESSION NO : 0002RJ073694 AGE : 21 Years SEX : Male DATE OF BIRTH :
DRAWN : 27/10/2018 16:00 RECEIVED : 29/10/2018 07:12 REPORTED : 03/11/2018 15:39
REFERRING DOCTOR : CLIENT PATIENT ID : 1805030173
Final ResultsTest Report Status Units
KRAS MUTATION DETECTION
KRAS MUTATION AT CODON 12 (EXON 2)
NOT DETECTED
DETECTED
KRAS MUTATION AT CODON 13 (EXON 2)
NOT DETECTED
DETECTED
BLOCK IDENTIFICATION NUMBER S-3175/18-A10
Interpretation(s)
KRAS MUTATION DETECTION-
Background: Somatic mutations of KRAS gene represent the most common alterations currently known in colon rectal cancer (CRC). In addition, subsets of NSCLC patients
also harbour KRAS mutation especially who have EGFR widltype genotype. KRAS mutation is found to be reported in 30-45 % of CRC patients, has shown to be a predictive
biomarker of resistance to anti-EGFR antibody therapy [Loupakis F et al 2009 Soeda H et al 2013].
Clinical utility: KRAS codons 12 and 13 mutations predict resistance to anti-EGFR monoclonal antibodies in metastatic colorectal cancer.
Test method: Pyrosequencing.
Result interpretation:
A)Positive: The result indicates that the patient’s tumor sample shows either KRAS codon 12 or codon 13 mutation. Presence of KRAS mutation in codon 12 or 13 is useful in
identifying patients who are likely to show resistance to anti-EGFR therapy in metastatic colorectal cancer. Based on American Society of Clinical Oncology Provisional Clinical
Opinion, treatment with anti-EGFR monoclonal antibody therapy is not recommended for patients harboring codon 12 or 13 mutation in the KRASgene.
B) Negative: The result indicates that the patient’s tumor sample do not show KRAS codon 12 and 13 mutation.
Limitations:
PCR is highly sensitive technique however inherent PCR inhibitors in the specimen may result into amplification failure.
Pyrosequencing has a sensitivity of 10% mutant allele. Tissues with less than 20% of tumor cells may not be detect mutation in KRAS codon 12 and 13.
The test will detect most common mutations in codon 12 and 13 of the KRAS gene. Mutations in other locations within the KRAS gene will not be detected.
References:
Loupakis F1, Ruzzo A, Cremolini C et al (2009). KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type
metastatic colorectal cancer. Br J Cancer. Aug 18 101(4):715-21.
Soeda H, Shimodaira H, Watanabe M, et al (2013). Clinical usefulness of KRAS, BRAF, and PIK3CA mutations as predictive markers of cetuximab efficacy in irinotecan- and
oxaliplatin-refractory Japanese patients with metastatic colorectal cancer. Int J Clin Oncol. Aug 18(4):670-7.
**End Of Report**
Please visit www.srlworld.com for related Test Information for this accession
Dr. Firoz Ahmad,PhD
Research Scientist and Senior
Manager - R&D
Dr. B. R. Das, PhD
Advisor and Mentor
R&D & Molecular Diagnostics
Dr. (COL) Prabal Deb
Director (Lab Operations) &
Chief Histopathologist
Page 1 Of 2
30. CYTOREDUCTIVE SURGERY & HEATED
INTRAPERITONEAL CHEMOTHERAPY (HIPEC)
• Indication: (limited) peritoneal metastases
• RCT: CRS+HIPEC (5FU infusion, IP MMC) (n=105)
Verwall et al, J Clin Oncol 21:3737-3743, 2003
31. 3507: CREST: RANDOMISED PHASE III STUDY OF STENTING AS A BRIDGE TO
SURGERY IN OBSTRUCTING COLORECTAL CANCER—RESULTS OF THE UK
COLORECTAL ENDOSCOPIC STENTING TRIAL (CREST) – HILL J, ET AL
Study objective
• To investigate the effects of endoluminal stenting vs emergency surgery on outcomes and QoL in patients with potentially
CRC
*Endoscopic/fluoroscopic technique with elective surgery
performed 1–4 weeks later. Hill et al. J Clin Oncol 2016; 34 (suppl): abstr 3507
R
1:1
PD
Stratification
• Curative intent based on pre-operative
staging investigations
Endoluminal stenting*
(n=123)Key patient inclusion criteria
• Left-sided CRC
• Radiological evidence of
obstruction
• No evidence of peritonitis
or perforation
(n=245)
PRIMARY ENDPOINTS
• Length of hospital stay
• 30-day mortality
SECONDARY ENDPOINTS
• Stenting completion, complication rate
• Presence/duration of stoma/anastomosis rate
• 6-month OS; 3-year DFS
• QoL, perioperative morbidity
PD
Surgical decompression
(n=122)
32. 3507: CREST: RANDOMISED PHASE III STUDY OF STENTING AS A BRIDGE TO
SURGERY IN OBSTRUCTING COLORECTAL CANCER—RESULTS OF THE UK
COLORECTAL ENDOSCOPIC STENTING TRIAL (CREST) – HILL J, ET AL
Key results
Hill et al. J Clin Oncol 2016; 34 (suppl): abstr 3507
Remaininginhospital(%)
0
10
20
30
40
50
60
70
80
90
100
0
Days in hospital
20 40 60 80 100 120 140 160 180
Surgery
Stenting
No.
patients
133
133
Obs.
92
86
No Events
Exp.
92.1
85.9
2P=1.0
3%
4%
Stenting Surgery
Hospital days (curative patients with complete
1 year data)
N
Median (IQR)
86
14.5 (9–24)
92
13.5 (9.5–22.5)
Deaths within 30 days of randomisation
N 5 6
Days from randomisation to death
Median (IQR) 7 (6–15) 5 (3–9)
Length of hospital stay
33. 3507: CREST: RANDOMISED PHASE III STUDY OF STENTING AS A BRIDGE TO
SURGERY IN OBSTRUCTING COLORECTAL CANCER—RESULTS OF THE UK
COLORECTAL ENDOSCOPIC STENTING TRIAL (CREST) – HILL J, ET AL
Key results (continued)
• QoL and critical care utilisations at 3 and 12 months were not significantly different
Conclusions
• In patients with potentially curable CRC, stenting as a bridge to surgery had an
80% clinical success rate and significantly reduced stoma formation
• Mortality, length of hospital stay and QoL were similar between stenting and emergency surgery
• Stenting appears to be a reasonable alternative to emergency surgery
*Assessed by Clavien-Dindo classification. Hill et al. J Clin Oncol 2016; 34 (suppl): abstr 3507
Stenting Emergency surgery
Stoma formation, % 46 69
p-value 0.001
All deaths, n/N 59/123 47/122
Deaths, cancer patients 58/120 47/109
Surgical complications* 48 45
34. 1. Patients with resectable metastatic disease at presentation
2. Patients with unresectable disease at presentation that becomes
potentially resectable after downstaging (conversion) with systemic
therapy
3. Patients who have potentially resectable metastatic disease but
who are not candidates for resective surgery
4. Patients with unresectable metastatic disease
PATIENTS WITH METASTATIC DISEASE CAN BE
CLASSIFIED INTO 4 GROUPS:
35. CASE DISCUSSION
WHAT IS YOUR PREFERRED CHOICE OF TREATMENT?
1. CHEMOTHERAPY
2. CHEMO + Mab
3. IMMUNOTHERAPY
36. THE LUXURY OF SO MANY OPTIONS: HOW DO WE
PERSONALIZE THERAPY?
Patient X
Patient Y
Patient Z
42. Resection
Maximising OS, while maintaining QoL
Treatment
strategy
Treatment
goal
Curative
surgery
10%
Classification
Upfront
resectable
MOST PATIENTS WITH mCRC HAVE INITIALLY
UNRESECTABLE DISEASE AT FIRST PRESENTATION:
INCREASING OS IS THE PRIMARY TREATMENT GOAL
20–30% 60–70%
Potentially
resectable
Permanently
unresectable
CT +
biologic
CT +
biologic
Relapse
Initially unresectable
43. COLON CANCER: MORE THAN 1 DISEASE
MSI vs MSS RAS WT vs
mutant
Right vs left vs
rectal
Young vs old
Stool flora typesBRAF WT vs
mutant
HER2
Molecular Anatomic
44. CRC : HCG BANGALORE
Veldore VH, Rao MR, Prabhudesai SA, Tejaswi R, Kakara S, Pattanayak S, et al. Prevalence of KRAS mutations in metastatic
colorectal cancer: A retrospective observational study from India. Indian J Cancer 2014;51:531-7.
Prevalence of KRAS mutation
(42.8%) in India is at par with world
literature that varies from 30% to
60%.
47. SEVERAL FACTORS INFLUENCE 1ST LINE
TREATMENT DECISIONS IN MCRC
1. et al. Lancet 2016;17:1426–1434; 4. Arnold D, et al. Ann Oncol 2017; doi: 10.1093.
Biomarker status1–3
Patient characteristics1
Primary tumor location4
48. SEVERAL FACTORS INFLUENCE 1ST LINE
TREATMENT DECISIONS IN MCRC
1. Van Cutsem E, et al. Ann Oncol 2016;27:1386–1422; 2. Lenz H-J, et al. Ann Oncol 2014;25 (suppl 4; Abstract No. 501O); 3. Stintzing S, et al.
Lancet 2016;17:1426–1434; 4. Arnold D, et al. Ann Oncol 2017; doi: 10.1093; 5. Heinemann V, et al. Lancet Oncol 2014;15:1065–1075; 6.
Venook A, et al. JAMA 2017;317:2392–2401.
*FIRE-3 did not meet its primary endpoint of significantly improving overall response rate (ORR) based on investigators’ read in
patients with KRAS (exon 2) wt mCRC;5 †CALGB/SWOG 80405 study did not meet its primary endpoint of significantly
improving overall survival in the cetuximab + CT arm vs bevacizumab + CT arm in patients with KRAS (exon 2) wt mCRC.6
CT, chemotherapy
• Including BRAF, MSI and RAS status1
• RAS status predicts outcomes with
anti-EGFR therapies1
• In RAS wt mCRC, cetuximab + CT is
associated with greater
improvements in ORR, OS and PFS
over bevacizumab + CT2,3*† [CALGB
SWOG/80405, FIRE-3]
Biomarker status1–3
Patient characteristics1
Primary tumor location4
49. CALGB/SWOG 80405: FIRST-LINE CT +
BEVACIZUMAB OR CETUXIMAB IN
KRAS-WT mCRC
• Multicenter, randomized, open-label phase III trial
• Primary endpoint: OS; secondary endpoints: PFS, TTF, DoR
• Conclusion: no difference in first line
Pts ≥ 18 yrs of age with KRAS-WT
(codons 12, 13), locally advanced
or mCRC; ECOG PS 0/1; no prior
systemic treatment
(N = 1137)
FOLFOX or FOLFIRI
+ Bevacizumab IV Q2W
(n = 559)
FOLFOX or FOLFIRI
+ Cetuximab IV Q1W
(n = 578)
29.0
29.9
10.8
10.4
mOS,
Mos
mPFS,
Mos
Stratified by CT (FOLFOX vs FOLFIRI), prior adjuvant
chemotherapy (yes vs no), prior pelvic radiotherapy (yes vs no)
50. 100
80
60
40
20
0
0 12 24 36 48 60 72 84 96 108
Mos From Study Entry
EventFree(%)
CALGB/SWOG 80405 (FOLFIRI/FOLFOX + BEV OR
CETUXIMAB): OS BY TUMOR LOCATION (RAS WT)
Bevacizumab
(n = 152 vs 78)
32.6
(28.3-36.2)
29.2
(22.4-36.9)
0.88
(0.62-1.25)
.50
OS, Mos (95% CI) HR
(95% CI)
P Value
Left Right
Cetuximab
(n = 173 vs 71)
39.3
(32.9-42.9)
13.7
(11.3-19.0)
0.55
(0.39-0.79)
.001
.
51. 2014.
CETUXIMAB IS THE 1ST LINE THERAPY THAT DEMONSTRATES
SIGNIFICANT SURVIVAL BENEFIT OVER BEVACIZUMAB IN
LEFT-SIDED RAS WT MCRC IN THE PHASE III
CALGB/SWOG 80405 TRIAL
40
30
20
0
MedianOS(months)
Phase III CALGB/SWOG 804051–3
10
39.3
32.6
+6.7
months
HR=0.77
(p=0.04)
Bevacizumab
+ FOLFOX/FOLFIRI
(n=152)
Cetuximab
+ FOLFOX/FOLFIRI
(n=173)
52. CETUXIMAB IS THE 1ST LINE THERAPY THAT DEMONSTRATES
SIGNIFICANT SURVIVAL BENEFIT OVER BEVACIZUMAB IN
LEFT-SIDED RAS WT MCRC IN THE PHASE III FIRE-3 TRIAL
38.3
Bevacizumab
+ FOLFIRI
(n=149)
Cetuximab
+ FOLFIRI
(n=157)
40
30
20
0
MedianOS(months)
Phase III FIRE-3
)
28.0
10
+10.3
months
HR=0.63
(p=0.002)
53. SEVERAL FACTORS INFLUENCE 1ST LINE
TREATMENT DECISIONS IN MCRC
1. Van Cutsem E, et al. Ann Oncol 2016;27:1386–1422; 2. Lenz H-J, et al. Ann Oncol 2014;25 (suppl 4; Abstract No. 501O);
3. Stintzing S, et al. Lancet 2016;17:1426–1434; 4. Arnold D, et al. Ann Oncol 2017.
Biomarker status1–3
Primary tumor location4
• Age
• Performance status
• Organ function
• Comorbidities
• Patient attitude, expectations and
preferencePatient characteristics1
54. MCRC TREATMENT DECISION
RECOMMENDATIONS: FIRST LINE
2L1L 3L 4L
RAS
mutation
RAS
wild type
RAS
wild type
RAS
wild type
Chemo +
anti-VEGF
Chemo +
anti-VEGF
Chemo +
anti-VEGF
Chemo +
anti-VEGF
Chemo +
anti-VEGF
Chemo +
anti-EGFR
Chemo +
anti-EGFR
Chemo +
anti-VEGF
Chemo +
anti-EGFR
Other
anticancer
therapy, BSC,
or clinical trial
Other
anticancer
therapy, BSC,
or clinical trial
Other
anticancer
therapy, BSC,
or clinical trial
Other
anticancer
therapy, BSC,
or clinical trial
REGORAFENI
B
or TAS-102
REGORAFENI
B
or TAS-102
REGORAFENI
B
or TAS-102
Left-sided
cancers
only
Anti-VEGF Anti-EGFR
Bevacizumab Cetuximab
PanitumumabRegorafenib
or TAS-102
Regorafenib
or TAS-102
Regorafenib
or TAS-102
Regorafenib
or TAS-102
55. MCRC TREATMENT DECISION
RECOMMENDATIONS: SECOND LINE
2L1L 3L 4L
RAS
mutation
RAS
wild type
RAS
wild type
RAS
wild type
Chemo +
anti-VEGF
Chemo +
anti-VEGF
Chemo +
anti-VEGF
Chemo +
anti-VEGF
Chemo +
anti-VEGF
Chemo +
anti-EGFR
Chemo +
anti-EGFR
Chemo +
anti-VEGF
Chemo +
anti-EGFR
Other
anticancer
therapy, BSC,
or clinical trial
Other
anticancer
therapy, BSC,
or clinical
trial
Other
anticancer
therapy, BSC,
or clinical
trial
Other
anticancer
therapy,
BSC, or
clinical trial
REGORAFENI
B
or TAS-102
REGORAFENI
B
or TAS-102
REGORAFENI
B
or TAS-102
Left-sided
cancers
only
Anti-
VEGF
Anti-
EGFR
Bevacizumab
Ramucirumab
Ziv-aflibercept
Cetuximab
Panitumumab
van Cutsem E, et al. Ann Oncol. 2016;27:1386-1422.
Regorafenib
or TAS-102
Regorafenib
or TAS-102
Regorafenib
or TAS-102
Regorafenib
or TAS-102
57. BIOFILM: A NEW CONCEPT OF TUMORIGENESIS
Biofilm may cause an increased
epithelial proliferation by
upregulation of the proinflammatory
IL-6 and
its downstream effector STAT3
Invasive polymicrobial bacterial
biofilms (bacterial aggregates
encased in a likely complex
matrix) predominantly (89%)
on right-sided tumors
Biofims associated with chronic
inflammation (e.g. CID)
Colon mucosal biofilm detection
may predict increased risk for
development of sporadic CRC
E-cadherin P-STAT3IL-6