The document discusses staging of lung cancer using the TNM system. It provides details on the T, N, and M descriptors for lung cancer staging. For the T descriptor, it notes changes in the 8th edition where tumor size cut-offs are more granular. For the N descriptor, it discusses exploratory subgroupings to classify single versus multiple lymph node metastases. For the M descriptor, it proposes subclassifying M1 metastases by single versus multiple organ involvement. Overall, the document reviews the TNM staging system for lung cancer and proposes some revisions for the 8th edition.
Presentación realizada por la Dra. Pilar Escudero del HCU Lozano Blesa, en el marco de la I Jornada de actualización e innovación en Oncología que tuvo lugar en el CIBA en enero de 2015.
This class covers what all physicians need to know about colorectal cancer (except prevention and screening, dealt with elsewhere). It is exceedingly simple, but accurate to the best of my knowledge. It is based on Harrison's 19th, Edition.
Presentación realizada por la Dra. Pilar Escudero del HCU Lozano Blesa, en el marco de la I Jornada de actualización e innovación en Oncología que tuvo lugar en el CIBA en enero de 2015.
This class covers what all physicians need to know about colorectal cancer (except prevention and screening, dealt with elsewhere). It is exceedingly simple, but accurate to the best of my knowledge. It is based on Harrison's 19th, Edition.
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
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
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Antimicrobial stewardship to prevent antimicrobial resistanceGovindRankawat1
India is among the nations with the highest burden of bacterial infections.
India is one of the largest consumers of antibiotics worldwide.
India carries one of the largest burdens of drug‑resistant pathogens worldwide.
Highest burden of multidrug‑resistant tuberculosis,
Alarmingly high resistance among Gram‑negative and Gram‑positive bacteria even to newer antimicrobials such as carbapenems.
NDM‑1 ( New Delhi Metallo Beta lactamase 1, an enzyme which inactivates majority of Beta lactam antibiotics including carbapenems) was reported in 2008
share - Lions, tigers, AI and health misinformation, oh my!.pptxTina Purnat
• Pitfalls and pivots needed to use AI effectively in public health
• Evidence-based strategies to address health misinformation effectively
• Building trust with communities online and offline
• Equipping health professionals to address questions, concerns and health misinformation
• Assessing risk and mitigating harm from adverse health narratives in communities, health workforce and health system
- 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
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
3. Variable Low risk Intermediate risk High risk
Diameter 1.5 1.5-2.2 2.3+
Age cut-off 45 60
Smoking status Never Current 1pack/d Current 1+ pack/d
Smoking cessatin Quit 7+ yrs ago Quit 7- yrs ago Never quit
Nodule
characteristics
Smooth Scalloped Corona radiata or
spiculated
Solitary pulmonary nodule
Radiologic features likely to be benign
Stability over 2+ yrs.
Benign calcification: central nidus, multiple punctate, “bulls-eye” and popcorn
SPN/GGO
Stable over 2 yrs
Benign calcification
Less than 4 mm in diameter
Stop
High-risk of cancer
Tissue biopsy
Less than 8 mm
Repeat CT in 3 mo
8+mm/Low-Intermediate risk
of cancer
PET-CT
11. Trends in incidence of lung cáncer
- Women
GLOBOCAN, 20
http://globocan.iarc.fr/old/FactSheets/cancers/lu
12. Jemal A, Siegel R, Ward E et al. Cancer Statistics, 2009 CA Cancer J Clin 2009 59: 225-249
Mortalidad 1930-2005 USA: Hombres / Mujeres
Lung cancer
Projected life-time risk of developing
lung cáncer is 6% and 8% in females
and males, respectively (in the US).
Tobacco consumption closely parallels
lung cancer incidence 20 years later.
13. Jemal A, Siegel R, Ward E et al. Cancer Statistics, 2009 CA Cancer J Clin 2009 59: 225-249
Incidencia/Mortalidad USA: Hombres
14. Incidencia Mortalidad
Jemal A, Siegel R, Ward E et al. Cancer Statistics, 2009 CA Cancer J Clin 2009 59: 225-249
Incidencia/Mortalidad USA: Mujeres
15. Lung Cancer: Incidence and Mortality
New cases in 2013: 228,190
- 40% with stage IV disease at
presentation (~ 90,000)
~ 160,000 deaths in 2012,
comparable to prostate,
pancreas, breast, and colon
cancer combined
5-yr relative survival rate:
3.7% for patients with
distant-stage disease
NCI. Non-small-cell lung cancer treatment (PDQ®). ACS. Cancer facts & figures: 2012. CDC. Lung cancer
rates by race and ethnicity. Howlader N, et al. SEER cancer statistics review.
Estimated Cancer Deaths
by Site, 2012
Other Cancers Lung Cancer
180,000
160,000
140,000
120,000
100,000
80,000
60,000
40,000
20,000
0
Lung
cancer
Prostate
Pancreas
Breast
Colon
16. Incidencia y mortalidad por de cáncer en Colombia
Registro Poblacional de Cáncer - Calihttp://rpcc.univalle.edu.co/
Cáncer del pulmón
17. Risk Factors for Lung Cancer
Smoking
– Current: 2000%
– Former: 900%
– ETS: 30%
– 1 new mutation per 15 cigarettes smoked
Lung cancer deaths due to smoking
– ~ 91% males and 80% females[1]
Environmental factors[2]
– Second-hand smoke 3% to 5%
– Radon 3% to 5%
– Industrial pollution 0% to 5%
Radiation exposure Rare
– Asbestos, radon, radiation, silicosis, and berylliosis, nickel, chromium, mustard
gas, Polycyclic Aromatic Hydrocarbons, bischloromethyl ether
– Arsenic exposure, talc, obesity, genetic factors
1. CDC. Lung Cancer. 2011.
2. American Cancer Society. Lung Cancer. 2011.
29. Complexities of Lung Cancer Pathogenesis Result in
Diverse Histologic Subtypes
SCC
(~ 25%)
SCLC
(~ 15%)
LPA
(formerly BAC)
(~ 5% to 10%)
Adenocarcinoma(~
45%)
Large Cell
(~ 5% to 10%)
NOS
(~ 10% to 30%)
Reprinted by permission from Macmillan Publishers Ltd:
Sun S, et al. Nat Rev Cancer. 2007; 7:778-790.
Travis WD, et al. J Clin Oncol. 2013;[Epub ahead of print].
33. Kris MG, et al. ASCO 2011. CRA7506. Johnson BE, et al. IASLC WCLC 2011. Abstract O16.01
Lung Cancer Molecular Consortium Analysis in
Lung Adenocarcinomas
No Mutation
Detected KRAS
22%
EGFR
17%EML4-AKL
7%
Double
Mutants 3%
BRAF 2%
PIK3CA 2%
HER2
MET AMP
MEK1
NRAS
AKT1
Erlotinib
Gefitinib
Afatinib
Selumetinib
Crizotinib
34. How to handle small tissue samples in lung cancer
p63 and TTF1
H&E
SCC Non-SCC (Adeno)
Genomics
SCLC
NeuroEndocrine
EGFR
ALK/EML4
ROS1
BRAF
Her2
p63+ TTF1+
PD-L1 by IHC
(in advanced NSCLC)
PD-L1 by IHC
(in advanced NSCLC)
Chromogranin
Synaptophysin
37. T-descriptor
Every cm counts…
Previous (TNM 7th)
T1a
T1a
T1b
T2a
T2a
T2b
T3
Rami-Porta R, J Thoracic Oncol, 2015
Proposed (TNM 8th)
Up to 1 cm: T1a
>1-2 cm: T1b
>2-3 cm: T1c
>3-4 cm: T2a
>4-5 cm: T2b
>5-7 cm: T3
>7 cm: T4
International Association for the Study of Lung Cancer, 2015
38. T – Primary Tumour
Tx Primary tumour cannot be assessed
T0 No evidence of primary tumour
T1 Tumour 3 cm or less in greatest diameter surrounded by lung or visceral pleura, without evidence
of main bronchus
T1a(mi) Mininally invasive adenocarcinoma
T1a Tumour 1 cm or less in greatest diameter
T1b Tumour more than 1 cm but not more than 2 cm
T1c Tumour more than 2 cm but not more than 3 cm
T2 Tumour more than 3 cm but not more than 5 cm; or tumour with any of the following features:
Involves main bronchus (without involving the carina), invades visceral pleura, associated with
atelectasis or obstructive pneumonitis that extends to the hilar region
T2a Tumour more than 3 cm but not more than 4 cm
T2b Tumour more than 4 cm but not more than 5 cm
T3 Tumour more than 5 cm but not more than 7 cm or one tha directly invades any of the following:
chest wall, phrenic nerve, parietal pericardium, or associated separate tumour nodule(s) in the
same lobe as the primary
T4 Tumours more than 7 cm or one that invades any of the following: diaphragm, mediastinum,
heart, great vessels, trachea, recurrent laryngeal nerve, oesophagus, vertebral body, carina;
separate tumour nodule(s) in a different ipsilateral lobe to that of the primary
39. N-descriptor
No changes in the TNM 8th Edition…
Exploratory subgrouping (for future validation)
- N1a: Single N1
- N1b: Multiple N1
- N2a1: Single N2 (skip metastasis)
- N2a2: Single N2 + N1
- N2b: Multiple N2
Asamura H et al. J Thoracic Oncol, 2015, in press
International Association for the Study of Lung Cancer, 2015
40. YOUR LOGO
Lymph-node stations in lung cancer:
General Plan
Supraclavicular:
- Station 1
Superior mediastinal:
- Stations 2-4
Aortic:
- Stations 5/6
Inferior mediastinal:
- Stations 7-9
N1 nodes:
- Stations 10-14
http://www.radiologyassistant.nl/en/p4646f1278c26f/mediastinum-lymph-node-map.html (Accessed 2017)
41. M-descriptor
• M1a: as it is
• M1b: single metastasis in a single organ
• M1c: multiple metastases in a single organ or
in several organs
42. N – Regional Lymph Nodes
Regional lymph nodes cannot be assessedNx
No regional lymph node metastasisN0
Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes
and intrapulmonary nodes, including involvement by direct extension
N1
Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s)N2
Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or
contralateral scalene or supraclavicular lymph node(s)
N3
M – Distant Metastasis
No distant metastasisM0
Distant metastasisM1
Separate tumour nodule(s) in a contralateral lobe; tumour with pleaural or
pericardial nodules or malignant pleural or pericardial effusion
M1a
Single extrathoracic metastasis in a single organM1b
Multiple extrathoracic metastases in one or several organsM1c
International Association for the Study of Lung Cancer, 2015
43. STAGE T N M
Occult TX N0 M0
0 Tis N0 M0
IA1 T1a(mi)/T1a N0 M0
IA2 T1b N0 M0
IA3 T1c N0 M0
IB T2a N0 M0
IIA T2b N0 M0
IIB T1a-T2b N1 M0
T3 N0 M0
IIIA T1a-T2b N2 M0
T3 N1 M0
T4 N0/N1 M0
IIIB T1a-T2b N3 M0
T3/T4 N2 M0
IIIC T3/T4 N3 M0
IVA Any T Any N M1a/M1b
IVB Any T Any N M1c
International Association for the Study of Lung Cancer, 2015
44.
45. 8th Edition of the TNM Classification
for Lung Cancer
N0 N1 N2 N3 M1a M1b M1c
T1a IA1 IIB IIIA IIIB IVA IVA IVB
T1b IA2 IIB IIIA IIIB IVA IVA IVB
T1c IA3 IIB IIIA IIIB IVA IVA IVB
T2a IB IIB IIIA IIIB IVA IVA IVB
T2b IIA IIB IIIA IIIB IVA IVA IVB
T3 IIB IIIA IIIB IIIC IVA IVA IVB
T4 IIIA IIIA IIIB IIIC IVA IVA IVB
International Association for the Study of Lung Cancer, 2015
46. 8th Edition of the TNM Classification
for Lung Cancer
N0 N1 N2 N3 M1a M1b M1c
T1a IA1 IIB IIIA IIIB IVA IVA IVB
T1b IA2 IIB IIIA IIIB IVA IVA IVB
T1c IA3 IIB IIIA IIIB IVA IVA IVB
T2a IB IIB IIIA IIIB IVA IVA IVB
T2b IIA IIB IIIA IIIB IVA IVA IVB
T3 IIB IIIA IIIB IIIC IVA IVA IVB
T4 IIIA IIIA IIIB IIIC IVA IVA IVB
International Association for the Study of Lung Cancer, 2015
Upfront resection feasible
Mostly palliative intentMostly unresectable
47. 8th Edition of the TNM Classification
for Lung Cancer
N0 N1 N2 N3 M1a M1b M1c
T1a IA1 IIB IIIA IIIB IVA IVA IVB
T1b IA2 IIB IIIA IIIB IVA IVA IVB
T1c IA3 IIB IIIA IIIB IVA IVA IVB
T2a IB IIB IIIA IIIB IVA IVA IVB
T2b IIA IIB IIIA IIIB IVA IVA IVB
T3 IIB IIIA IIIB IIIC IVA IVA IVB
T4 IIIA IIIA IIIB IIIC IVA IVA IVB
International Association for the Study of Lung Cancer, 2015
Surgery, followed by adjuvant chemotherapy
Systemic therapyMultimodal therapy:
(ie, Chemo-Radiation, followed by Immunotherapy)
50. If surgery is considered
Upfront assessment
Potentially resectable
Potentially resectable with
some risk of incomplete
resection
Not resectable
SURGERY IN STAGE III NSCLC
Eberhardt WEE, De Ruysscher D, Weder W, et al. 2nd ESMO Consensus Conference in Lung Cancer: locally advanced stage III non-small-cell lung cancer. Ann Oncol.
2015;26(8):1573-1588. doi:10.1093/annonc/mdv187.
51. If surgery is considered
Optimal pre-op work-up
Histopathology for PET-
detected isolated single met
Primary tumour of >3 cm large
axis, central tumours, cN1, CT-
enlarged lymph nodes with
small axis >1 cm
Symptomatic / High Risk (T4N2
PET-CT
Assessment of mediastinal
disease in PET+ or suspicious
lesions
Brain MRI
or N3)
SURGERY IN STAGE III NSCLC
Eberhardt WEE, De Ruysscher D, Weder W, et al. 2nd ESMO Consensus Conference in Lung Cancer: locally advanced stage III non-small-cell lung cancer. Ann Oncol.
2015;26(8):1573-1588. doi:10.1093/annonc/mdv187.
52. YOUR LOGO
Tratamiento de NSCLC temprano
(Estadíos I-IIIA)
CIRUGÍA EN NSCLC
• Se recomienda cirugía para T resecables (T1-T3), sin
compromiso mediastinal (N0-N1)
- Lobectomía o pneumonectomía (+ disección ganglionar
mediastinal).
- Considerar SBRT en casos selectos (No candidatos a
cirugía)
• No se recomienda cirugía para pacientes con T4, N2 o N3 -
Si no hay metástasis, proceder con quimiorradioterapia
(Cisplatino + Etopósido)
53. Physiologic staging
Appropriate FEV1
- Greater than 2L for pneumonectomy
- Greater than 1.5L for lobectomy
VOmax greater than 15 mL/(kg.min)
Surgery contraindicated in:
- AMI within the last 3 months
- AMI within the last 6 months (relative)
- Uncontrolled arrhythmias
- FEV1 less than 1L
- DLCO less than 40%
- Severe pulmonary hypertension
- pCO2 greater than 45 mmHg
55. YOUR LOGO
NSCLC: Prognostic Factors
Factors correlated with adverse prognosis in resected
patients
- Presence of pulmonary symptoms
- Large tumor size (>3 cm)
- Nonsquamous histology
- Metastases to multiple lymph nodes within a TNM-defined nodal station
- Vascular invasion
For patients with inoperable disease, prognosis is adversely
affected by poor performance status, weight loss of more than
10%, male gender
Advanced age alone has not been shown to influence
response or survival with therapy
NCI. Non-small-cell lung cancer treatment (PDQ®).
56. YOUR LOGO
Tratamiento de NSCLC temprano
(Estadíos I-IIIA)
RADIOTERAPIA ADYUVANTE
• Estadíos I, II, IIIA no quirúrgicos
• Luego de cirugía si márgenes comprometidos
• Luego de cirugía si ganglios linfáticos mediastinales
comprometidos (estadío IIIA).
57. YOUR LOGO
Tratamiento de NSCLC temprano
(Estadíos I-IIIA)
QUMIOTERAPIA ADYUVANTE
- Estadíos II-III (algunos incluyen Ib)
- Dupletas basadas en cisplatino x4 meses
61. Potentially resectable stage III, but high
risk of incomplete resection
Superior sulcus tumors
Induction ChemoRT followed by Surgery
POTENTIALLY RESECTABLE STAGE III NSCLC
62. Potentially resectable stage III, but high
risk of incomplete resection
Selected Central T3-T4 tumors
Induction ChemoRT followed by Surgery*
T4N0-1
Definitive ChemoRT
Surgery within 4 weeks after RT finished
POTENTIALLY RESECTABLE STAGE III NSCLC
Eberhardt WEE, De Ruysscher D, Weder W, et al. 2nd ESMO Consensus Conference in Lung Cancer: locally advanced stage III non-small-cell lung cancer. Ann Oncol.
2015;26(8):1573-1588. doi:10.1093/annonc/mdv187.
Eberhardt W, Gauler T, Pöttgen C et al. Phase III study of surgery versus definitive concurrent chemoradiotherapy boost in patients with operable (OP+) stage
IIIA(N2)/selected IIIb non-small cell lung cancer (NSCLC) following induction chemotherapy and concurrent CRTx (ESPATUE). J Clin Oncol 2014; 32(5s suppl): abstr
63. Unresectable Stage III disease
Unresectable stage III disease
Bulky and multiple mediastinal nodal involvement
Stage IIIB disease based on unresectable T4
Stage IIIB disease based on N3
Eberhardt WEE, De Ruysscher D, Weder W, et al. 2nd ESMO Consensus Conference in Lung Cancer: locally advanced stage III non-small-cell lung cancer. Ann Oncol.
2015;26(8):1573-1588. doi:10.1093/annonc/mdv187.
64. Unresectable Stage III disease
Unresectable stage III disease
Definitive Concurrent ChemoRT
Sequential ChemoRT
Palliative therapy
65. YOUR LOGO
The many faces of stage III NSCLC
Post surgical N2/N3+ disease - Adjuvant CT
- Consider adjuvant RT
Known N2/N3+ disease
- Definitive chemo RT with platin-based chemotherapy
- Consider chemo RT with platin-based chemotherapy followed by surgery (if
lobectomy is sufficient) in non-bulky N2 disease.
Superior sulcus tumors - Arise in the apex of the lungs
- Invade the 2nd and 3rd ribs, brachial plexus, subclavian vessels, stallate
ganglion and vertebral body
- Pancoast syndrome: pain in the shoulder or chest wall or radiate to the neck and ulnar
aspect of the upper limbs. - Horner’s syndrome
- Neoadjuvant Chemo-RT followed by surgery (if not N2/N3 disease)
- Excellent LT OS: 50+%
66. Stage IV - NSCLC – PS 0-1
NSCLC without “Driver” – PD-L1<50%
NSCLC
Squamous*
NSCLC
Non-squamous
CT with Platinum +
Pemetrexed +
Pembrolizumab
CT with Platinum+
Gemcitabine or Paclitaxel
*Bevacizumab is contraindicated due to fatal bleeding
*Pemetrexed is ineffective in squamous histology
67. Stage IV - NSCLC – PS 0-1
NSCLC without “Driver” – PD-L1≥50%
NSCLC
Squamous*
NSCLC
Non-squamous
Pembrolizumab
Pembrolizumab
MLM2018
70. Inmunología tumoral
Cebado
(priming) y
activación de
las células T
Célula
tumoral
PD-1
PD-L1
PD-L2
Receptor de
células T
MHC-1
CD28
Shp-2
B7.1
Célula
DendríticaLinfocito T
CD8+/Citotóxi
co
Co-estimuladora CD28 Co-estimuladora B7.1
73. Inmunología tumoral
Activación
de la
respuesta
inmunológi
ca CD8
efectora
Célula
tumoral
PD-1
PD-L1
PD-L2
Receptor de
células T
MHC-1
CD28
Shp-2
B7.1
Linfocito T
CD8+/Citotóxi
co
Antígeno + MHC-
1
Receptor de células T (TCR)
+++
Respuesta inmune
antitumoral
Presente
76. Inmunología tumoral
Las células
tumorales
expresan PD-L1
(PD-L2) cuando
hay estimulación
continuada del
IFN-Gamma,
"apagando" al
linfocito T
Célula
tumoral
PD-1
PD-L1
PD-L2
Receptor de
células T
MHC-1
CD28
Shp-2
B7.1
Linfocito T
CD8+/Citotóxi
co
IFN-γ
IFN-
γR
PD-L1
PD-1
- - -
Respuesta inmune
antitumoral
Frenada
78. Reck M, et al. N Engl J Med. 2016;375:1823-1833.
Pembro
(n = 154)
CT
(n = 151)
Median PFS, mos 10.3 6.0
HR (95% CI) 0.50 (0.37-0.68; P <
.001)
KEYNOTE-024: PFS
0
10
20
30
40
50
60
70
80
90
100
0 3 6 9 12 15 18
Mos
PFS(%)
Pts at Risk, n
62%
50%
48%
15%
79. Stage IV - NSCLC – PS 0-1
NSCLC with “Driver”
mEGFT
mALK/RO
S1
TKIs anti EGFR
(Osimertinib or Erlotinib
or Gefitinib or Afatinib)
TKIs anti ALK/ROS1
(Alectinib or Crizotinib)
83. EGFR in NSCLC: two distinct
pathways
Nucleus
Adaptor
Survival
PIP2
PI3K
PIP3
PTEN
AKT
Apoptosis
regulators
Proliferation
Adaptor
Transcription
factors
MAPK
MEK
RAFGTP-RASGDP-RAS
Sordella, et al. Science 2004
ATP ATP
Greater signalling through the
MAPK pathway producing
excessive cell proliferation
Higher affinity for ATP than
mutant receptor, so greater
competition with EGFR TKIs for
binding sites; higher
concentrations needed to inhibit
Successful inhibition of wild-type
EGFR reduces proliferation and
halts tumour growth
Higher incidence of stable disease
EGFR
wild-type
84. EGFR in NSCLC: two distinct pathways
ATP
Nucleus
Adaptor
Survival
PIP2
PI3K
PIP3
PTEN
AKT
Apoptosis
regulators
Proliferation
Adaptor
Transcription
factors
MAPK
MEK
RAFGTP-RASGDP-RAS
Sordella, et al. Science 2004
ATP
Preferential signalling through the PI3K-
mediated anti-apoptotic pathway –
‘oncogene addiction’
Reduced affinity for ATP means EGFR TKIs
have less competition for binding sites;
lower concentrations sufficient to inhibit
Successful inhibition of mutated EGFR
produces ‘apoptotic shock’
Higher incidence of complete or partial
response
EGFR
mutation
+ve
85. EGFR mutation +ve NSCLC:
different epidemiology
Majority of mutations are exon 19
deletions or L858R point mutations
in exon 21
EGFR
Chromosome 7
Shigematsu, et al. JNCI 2005; Murray, et al. JTO 2008
n=3,303
Exons 1–16
Exon 17
Exons 18–24
Exons 25–28
Extracellular domain
Transmembrane domain
TK domain
Regulatory domain
EGFR transcript EGF protein
Exon 18 Exon 19 Exon 20 Exon 21
50
40
30
20
10
0
Incidence(%)
87. SEER Fact Sheet
Distribución porcentual del estadío a la
presentación y supervivencia a 5 años
de cáncer de pulmón
Estadío a la presentación
Supervivencia a 5 años
90. Carcinoma broncogénico de
células pequeñas (SCLC)
Generalidades
- Menos común que el NSCLC (1/6, aprox.)
- Mayor asociación con tabaquismo
- Diseminación a distancia mucho más precoz en la
historia natural
- El espectro más agresivo de neoplasias
neuroendocrinas
91. Carcinoma broncogénico de
células pequeñas (SCLC)
Patología –
- Carcinoma de células pequeñas (SCLC)
- Célula pequeña, redonda y azul.
- Tiñe positivo para cromogranina y sinaptofisina (marcadores
neuroendocrinos)
Patrones de diseminación
- Masa central con extenso compromiso hiliar y mediastinal.
- Metástasis al:
- Hueso,
- Hígado,
- Cerebro,
- Pulmón,
- Adrenales.
92. SCLC
Estadificación
- ESTADÍO LIMITADO:
- T1-4 (excluyendo derrame pleural) N0-3M0:
- Usualmente se puede cubrir en un campo de radioterapia.
- ESTADÍO EXTENDIDO:
- Estadío IV: M1, y estadío III con derrame pleural.
- Supervivencia a 5 años
- Estadío I:
- Supervivencia a largo plazo del 70% (luego de cirugía y quimioterapia).
- Estadío Limitado:
- Supervivencia mediana 4 meses sin tratamiento,
- Supervivencia mediana 17 meses
- Curación en el 5-10%.
- Estadío Extendido:
- Supervivencia mediana 2-4 meses sin tratamiento.
- Se incrementa a 8-10 meses con terapia actual
- Aproximadamente 3% se curan
93. Small-Cell Lung Cancer: work-up and management
CT-Chest/Abdomen + Brain MRI +/- Bone Scan
SCLC
Stage I All others
PET-CT + Brain MRI
Confirmed Stage I
Surgery + EP
Limited-Stage Extended-stage
EP + RT + PCI EP +/- PCI
EP: Etoposide + Cisplatin x4 months
70% LT survival Median OS: 20 months Median OS: 9 months
95. YOUR LOGO
Lymph-node stations in lung cancer:
General Plan
Supraclavicular:
- Station 1
Superior mediastinal:
- Stations 2-4
Aortic:
- Stations 5/6
Inferior mediastinal:
- Stations 7-9
N1 nodes:
- Stations 10-14
http://www.radiologyassistant.nl/en/p4646f1278c26f/mediastinum-lymph-node-map.html (Accessed 2017)
96. YOUR LOGO
N-stage in lung cancer
http://www.radiologyassistant.nl/en/p4646f1278c26f/mediastinum-lymph-node-map.html (Accessed 2017)
97. YOUR LOGO
N-Stage in lung cancer
1. Station 1: Low cervical, supraclavicular, sternal notch lymph-nodes
2. 2L/2R: Upper paratracheal (R and L)
3. 4L/4R: Lower paratracheal
http://www.radiologyassistant.nl/en/p4646f1278c26f/mediastinum-lymph-node-map.html (Accessed 2017)
98. YOUR LOGO
N-stage in lung cancer
3. Prevascular and Prevertabral nodes
Station 3 nodes are not adjacent to the trachea like station 2 nodes.
They are either:
3A anterior to the vessels or
3B behind the esophagus, which lies prevertebrally.
Station 3 nodes are not accessible with mediastinoscopy.
3B nodes can be accessible with endoscopic ultrasound (EUS).
http://www.radiologyassistant.nl/en/p4646f1278c26f/mediastinum-lymph-node-map.html (Accessed 2017)
99. YOUR LOGO
N-Stage in lung cancer
2L/2R: Upper paratracheal (R and L)
3A: Prevascular
100. YOUR LOGO
N-Stage in lung cancer
4R. Right Lower Paratracheal
Upper border: intersection of caudal margin of innominate (left
brachiocephalic) vein with the trachea. Lower border:lower border
of azygos vein.
4R nodes extend to the left lateral border of the trachea.
http://www.radiologyassistant.nl/en/p4646f1278c26f/mediastinum-lymph-node-map.html (Accessed 2017)
101. YOUR LOGO
N-Stage in lung cancer
4R.Lower Paratracheal
From the intersection of the caudal margin of innominate (left brachiocephalic) vein with the trachea to
the lower border of the azygos vein.
4R nodes extend from the right to the left lateral border of the trachea.
4L.Lower Paratracheal
From the upper margin of the aortic arch to the upper rim of the left main pulmonary artery.
Aortic Nodes 5-6
5. Subaortic
These nodes are located in the AP window lateral to the ligamentum arteriosum.
These nodes are not located between the aorta and the pulmonary trunk but lateral to these vessels.
6. Para-aortic
These are ascending aorta or phrenic nodes lying anterior and lateral to the ascending aorta and the aortic arch.
http://www.radiologyassistant.nl/en/p4646f1278c26f/mediastinum-lymph-node-map.html (Accessed 2017)
102. YOUR LOGO
N-Stage in lung cancer
Aortic Nodes 5-6
5. Subaortic
These nodes are located in the AP window lateral to the ligamentum arteriosum.
These nodes are not located between the aorta and the pulmonary trunk but lateral to
these vessels.
6. Para-aortic
These are ascending aorta or phrenic nodes lying anterior and lateral to the ascending
aorta and the aortic arch.
103. YOUR LOGO
N-Stage in lung cancer
4R. Right Lower Paratracheal
Upper border: intersection of caudal margin of innominate (left brachiocephalic)
vein with the trachea.
Lower border:lower border of azygos vein.
4R nodes extend to the left lateral border of the trachea.
6. Para-aorticThese are ascending aorta or phrenic nodes lying anterior and lateral to the ascending aorta
and the aortic arch. http://www.radiologyassistant.nl/en/p4646f1278c26f/mediastinum-lymph-node-map.html (Accessed 2017)
104. YOUR LOGO
N-Stage in lung cancer
7. Subcarinal nodes
These nodes are located caudally to the carina of the trachea, but are not associated with the
lower lobe bronchi or arteries within the lung.
On the right they extend caudally to the lower border of the bronchus intermedius.
On the left they extend caudally to the upper border of the lower lobe bronchus.
On the left a station 7 subcarinal node to the right of the esophagus.
10 Hilar nodes
Hilar nodes are proximal lobar nodes, distal to the mediastinal pleural reflection and nodes
adjacent to the intermediate bronchus on the right.
Nodes in station 10 - 14 are all N1-nodes, since they are not located in the mediastinum.
105. YOUR LOGO
N-Stage in lung cancer
8 Paraesophageal nodes
These nodes are below the carinal nodes and extend caudally to the diafragm.
On the left an image below the carina.
To the right of the esophagus a station 8 node.
10 Hilar nodes
Hilar nodes are proximal lobar nodes, distal to the mediastinal pleural reflection and nodes
adjacent to the intermediate bronchus on the right.
Nodes in station 10 - 14 are all N1-nodes, since they are not located in the mediastinum.
http://www.radiologyassistant.nl/en/p4646f1278c26f/mediastinum-lymph-node-map.html (Accessed 2017)
106. YOUR LOGO
N-Stage in lung cancer
7. Subcarinal nodes
These nodes are located caudally to the carina of the trachea, but are not associated with the
lower lobe bronchi or arteries within the lung.
On the right they extend caudally to the lower border of the bronchus intermedius.
On the left they extend caudally to the upper border of the lower lobe bronchus.
On the left a station 7 subcarinal node to the right of the esophagus.
10 Hilar nodes
Hilar nodes are proximal lobar nodes, distal to the mediastinal pleural reflection and nodes
adjacent to the intermediate bronchus on the right.
Nodes in station 10 - 14 are all N1-nodes, since they are not located in the mediastinum.
107. YOUR LOGO
N-Stage in lung cancer
9. Pulmonary ligament nodes
Pulmonary ligament nodes are lying within the pulmonary ligament, including those
in the posterior wall and lower part of the inferior pulmonary vein. The pulmonary
ligament is the inferior extension of the mediastinal pleural reflections that surround
the hila.
http://www.radiologyassistant.nl/en/p4646f1278c26f/mediastinum-lymph-node-map.html (Accessed 2017)
108. YOUR LOGO
N-Stage in lung cancer
Stations 10 - 14. N1 lymph-nodes
Hilar, lobar, segmental and subsegmental
Stations 10-14 are NOT mediastinal lymph-nodes.
http://www.radiologyassistant.nl/en/p4646f1278c26f/mediastinum-lymph-node-map.html (Accessed 2017)
109. YOUR LOGO
N-Stage in lung cancer
http://www.radiologyassistant.nl/en/p4646f1278c26f/mediastinum-lymph-node-map.html (Accessed 2017)