CANCER DE

PULMON

DR.JULIO GUEVARA
HOSPITAL ALMENARA
UNMSM 2023
 Lung cancer global incidence
and mortality
• Lung cancer causes the most cancer-related deaths worldwide1

Lung Cancer Incidence*2 Lung Cancer Mortality*2

27.4+ 15.8–27.4 8.0–15.8 2.9–8.0 <2.9 No data 22.2+ 14.2–22.2 7.4–14.2 2.7–7.4 <2.7 No data

• In the US: ~221,200 new cases and ~158,000 deaths in 20153

• In the EU: ~410,200 new cases in 2012 and ~279,400 deaths in 20151,4
* Estimated ASRs per 100,000. Both sexes, all ages.
ASR = age standardized ratio.
1. GLOBOCAN 2012: Population Fact Sheets. Available at: http://globocan.iarc.fr/Pages/fact_sheets_population.aspx. Accessed
October 13, 2015. 2. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. Available at:
http://globocan.iarc.fr/Pages/Map.aspx. Accessed October 13, 2015. 3. ACS Lung Cancer Statistics. Available at:
http://www.cancer.org/cancer/lungcancer-non-smallcell/detailedguide/non-small-cell-lung-cancer-key-statistics. Accessed October 13,
2015. 4. Malvezzi M, et al. Ann Oncol. 2015:1-8. doi:10.1093/annonc/mdv001.
Most frequent cancers: both sexes

Globocan 2008
Most frequent cancers in Peru

Globocan 2008
 CASOS NUEVOS HOSPITAL ALMENARA - 2013
N° CIE - 10 Diagnostico N° Casos % % Acum

1 C50 TUMOR MALIGNO DE LA MAMA 172 12.37% 12.37%

2 C16 TUMOR MALIGNO DEL ESTOMAGO 140 10.06% 22.43%

3 C61 TUMOR MALIGNO DE LA PROSTATA 115 8.27% 30.70%

4 C18-C20 TUMOR MALIGNO DEL COLON Y RECTO 97 6.97% 37.67%

5 C53 TUMOR MALIGNO DEL CUELLO DEL UTERO 94 6.76% 44.43%

6 C82-C85 LINFOMA NO HODGKIN 88 6.33% 50.75%

7 C34 TUMOR MALIGNO DEL PULMON 77 5.54% 56.29%

8 C73 TUMOR MALIGNO DE LA GLANDULA TIROIDES 76 5.46% 61.75%

9 C44 TUMOR MALIGNO DE LA PIEL 70 5.03% 66.79%

10 C91-C95 LEUCEMIA 58 4.17% 70.96%

11 C71 TUMOR MALIGNO DEL ENCEFALO 38 2.73% 73.69%

12 C64 TUMOR MALIGNO DEL RIÑON 36 2.59% 76.28%

13 C67 TUMOR MALIGNO DE LA VEJIGA URINARIA 35 2.52% 78.79%

14 C78-C79 TUMOR MALIGNO SECUNDARIO 26 1.87% 80.66%

15 D32-D33, D43 TUMOR BENIGNO DEL SNC 23 1.65% 82.31%

16 C56 TUMOR MALIGNO DEL OVARIO 15 1.08% 83.39%

17 C62 TUMOR MALIGNO DEL TESTICULO 14 1.01% 84.40%

18 C22 TUMOR MALIGNO DEL HIGADO 13 0.93% 85.33%

19 C25 TUMOR MALIGNO DEL PANCREAS 13 0.93% 86.27%

20 C43 MELANOMA MALIGNO DE PIEL 13 0.93% 87.20%

 NSCLC
• NSCLC compromises 80 % of the cases of
cancer of lung
• High mortality
• The majority of the cases appears with
advanced disease:
~ 20 % EC IIIA/IIIB (poor forecast)
> 50 % EC IV (limited options of treatment)
• Many patients unable to tolerate conventional
treatments
Okike N, Bernatz PE, Woolner LB. Ann Thorac Surg. 1976;22:270-275.
American Cancer Society: Cancer facts and figures. 1999, Atlanta GA.
Mountain C. Chest. 1997;111:1710-1717.
 Lung cancer – an ongoing
struggle
• Lung cancer is the leading 28.4% 20.3%

16.3%

cause of cancer death globally 11.6%

9%

22.4%
– 1.3 million per annum % of cancer deaths
attributable to lung cancer
– Survival at 5yrs is <15%
– 2 people die of lung cancer every minute1

• Success rates for new

therapies is very low Development lifecycle of
new lung cancer
– Only 2% of investigational lung cancer therapies
1. Parkin DM. Global lung2cancer statistics, 2002. CA Cancer J Clin (2005). 55. 74 – 108.
treatments eventually reach patients
Figures = 1.18 million deaths per year / 365 days = 3,232 deaths per day / 24 hours = 134 deaths per hour/60 minutes = 2.24 deaths per minute.
2. BIO (Biotechnology Industry Organization) and BioMedTracker study - http://www.bio.org/news/pressreleases/newsitem.asp?id=2011_0214_02.
 FACTORES DE RIESGO
• Hábito tabáquico principal FR; 15% de los fumadores
crónicos; cigarros/día, años que fuma, edad de inicio,
contenido de alquitrán y nicotina, etc.
• Tabaquismo pasivo 5% de las muertes; aumento del
20% de riesgo.
• Sexo Incidencia varón/mujer=2/1.
• Etnia varones de raza negra.
• Polución atmosférica.
• Enfermedades respiratorias fibrosis pulmonar
idiopática y EPOC.
• Predisposición hereditaria.
• Factores ocupacionales radón, asbesto,
compuestos de arsénico, etc.
 Complexities of lung cancer pathogenesis result in diverse histologic subtypes

Presented By Martin Edelman at 2014 ASCO Annual Meeting

 Histological subtypes of NSCLC
Squamous (SQ)1
• 25%–30% of all lung cancer
• Often linked to a history of smoking
• Tend to be found in the middle of the lungs, near a
bronchus
Non-squamous: large cell carcinoma (LC)
• Comprises ~3% of all NSCLC2
• May appear in any part of the lung1
Non-squamous: adenocarcinoma (ADC)1
• Comprises ~40% of all NSCLC
• Most predominant histology type in non-smoking–
related cases
• Usually originates in the peripheral lung tissue
Not otherwise specified (NOS)
• Comprises ~25% of all NSCLC2

NSCLC = non-small cell lung cancer.

1. American Cancer Society. Lung Cancer (Non-Small Cell). Available at:
http://www.cancer.org/acs/groups/cid/documents/webcontent/003115-pdf. Accessed October 18, 2015. 2. SEER Cancer Statistics
Review, 1975-2007. Available at: http://seer.cancer.gov/csr/1975_2007. Accessed October 18, 2015
 CARCINOMA DE CÉLULAS
PEQUEÑAS
• 20% de los tumores malignos de pulmón; más frecuente de los de
tipo neuroendocrino.
• Origen: células de Kulchitsky o células basales de tipo
neuroendocrino L-dopa decarboxilasa, GRP y enolasa
neuroespecífica.
• Localización central y se asocia con adenopatías mediastínicas.
• Células de pequeño tamaño, escaso citoplasma y núcleo
hipercromático, abundante mitosis y necrosis.
• Extrema malignidad, fácil metástasis.
• Carcinoma de células pequeñas combinado (20%) más localizado y
mejor pronóstico.
Cancer is heterogenous
6a EDICIÓN DEL TNM 7a EDICIÓN DEL TNM

T1: ≤ 2 cm T1a
T1: > 2 cm, pero ≤ 3 cm T1b
T2: > 3 cm, pero ≤ 5 cm T2a
T2: > 5 cm, pero ≤ 7 cm T2b
T2: > 7 cm T3

Nódulos en el mismo lóbulo (T4) T3

Nódulos en otro lóbulo ipsilateral (M1) T4
Afectación pleural/pericárdica (T4)

M1a

Mtts. pulmón contralateral (M1) M1a

Mtts. extratorácicas (M1) M1b

• Los cálculos estadísticos determinaron tres puntos de
corte en 2, 5 y 7 cm, que, anadidos al valor de 3 cm,
frontera entre T1 y T2, dieron lugar a 5 grupos de
tumores con supervivencia significativamente peor a
medida que se hacía mayor el diámetro tumoral.
• Los grupos y sus tasas de supervivencia a los 5 anos
fueron: T1 ≤2 cm, 77%; T1 >2cm y ≤3cm, 71%; T2 >3cm
y ≤5 cm, 58%; T2 >5cm y ≤7cm, 49%, y T2 >7cm, 35%.
• La afectación del pericardio parietal se considera T3 pero
la del liquido pericárdico o pericardio visceral es M1a.
• El derrame pleural maligno es M1a .
• La afectación del nervio frénico se considera T3.
• La afectación del nervio recurrente , síndrome de cava
superior compresión de la tráquea o esófago se
considera T4.
• Si existe nódulos tumorales en el mismo lóbulo que el
tumor primario se considera T3, si están en el mismo
pulmón pero en distinto lóbulo se considera T4 ,y si están
en el otro pulmón se considera M1a.
Estadios clinicos
 Aspectos Clínicos

Síntomas Frecuencia (%)

Tos 70-80
Dolor Torácico 50
Anorexia–Pérdida de peso 50
Hemoptisis 30
Disfonía 15
Hipocratismo digital 5
Sibilancias 2
 Síndromes Paraneoplásicos
1. Sd Osteoarticular
• Son los más frecuentes.
• Principalmente en Ca Epidermoide.
• Producción ectópica de hormona del crecimiento.
• Hipocratismo digital, dolores osteoarticulares.

2. Sd Musculares
• Principalmente en Ca de Cel pequeñas
• Polimiositis, miopatía carcinomatosa, sd
miasteiforme (S de Eaton Lambert)
 Síndromes Paraneoplásicos
3. Sd Neurológicos
• En muchos casos es el inicio de la enfermedad.
• Principalmente en Ca de cel pequeñas.
• Degeneración subaguda del cerebelo,
neuropatía periférica, encefalitis límbica, neuritis
óptica, neuropatía sensorial o motora.

4. Sd Vasculares
• Producción acelerada de tromboplastina ?
• No existe relación con tipo histológico.
• Tromboflebitis periférica migratoria y recurrente,
endocarditis verrucosa no bacteriana
 Síndromes Paraneoplásicos
5. Sd Hematológicos
• No relación con tipo histológico.
• Anemia hemolítica, anemia por alteraciones del
metabolismo del hierro, poliglobulias, púrpuras
fibrinolíticas, reacciones leucemoides y CID.

6. Sd Cutáneo-mucosos
• Patogenia relacionada a producción ectópica de
la hormona estimulante de los melanocitos.
• Principalmente en Ca de cl pequeñas.
• Hiperpegmentación y acantosis nigricans.
 Síndromes Paraneoplásicos
7. Sd endocrinos

• Patogenia relacionada con producción ectópica

de sustancia con acción hormonal.

7.1 Hipercorticismo Suprarrenal, con o sin S de

Cushing, ACTH, (Ca de cel pequeñas)
7.2 Hipercalcemia sin hiperparatiroidismo ni
metástasis ósea, producción ectópica de
paratohormona o de PGs (Ca epidermoide)
 Frecuencia de compromiso metastásico

• Ganglio cervical 15-60%

• Hígado 1-35%
• Hueso 25%
• SNC 23%
• Corazón , pericardio 23%
• Adrenal 2-22%
• Pleura 8-15%
Grippi Ma.Sem Roentgenol,
1990
 Metástasis
• Sistema nervioso central: cefalea, TAC
de cerebro o RMN.

• Hígado: bioquímica hepática, TAC

abdominal, ecografía hepática.

• Huesos: dolor óseo localizado, calcio

sérico, gammagrafía ósea con tecnecio.
 Introducción
• La mayoría de los pacientes con cáncer
de pulmón son diagnosticados con
enfermedad avanzada (estadio IIIb / IV).
• Convencional:
1. Cirugía
2. Quimioterapia
3. Radiación
4. Bloqueadores de EGFR
 Cirugía
La cirugía, llevada a cabo por un cirujano torácico, se emplea para
extirpar el cáncer. Algunos tumores son inoperables a causa de su
tamaño o de su localización, y algunos pacientes no pueden ser
intervenidos
por forma
De otras razones médicas.
global,
existen tres Segmentectomía
tipos de
intervención
quirúrgica
en el cáncer
Lobectomía
del pulmón.

Neumonectomía
✔ Linfadenectomía
mediastínica
QUIMIOTERAPIA
CONTINUA
VIGENTE ????
 Is Chemotherapy Beneficial in NSCLC?

Presented By Martin Edelman at 2014 ASCO Annual Meeting

 Slide 13

Presented By Martin Edelman at 2014 ASCO Annual Meeting

 Post 1995 Meta-Analysis :<br />NSCLC Randomized Adjuvant Platinum Trials

Presented By Heather Wakelee at 2014 ASCO Annual Meeting

 Long Term Adjuvant Benefit?

Presented By Heather Wakelee at 2014 ASCO Annual Meeting

 NCCN Guidelines

Presented By Heather Wakelee at 2014 ASCO Annual Meeting

 Maintenance Trials

Presented By Martin Edelman at 2014 ASCO Annual Meeting

 Targeted Therapy For Lung Cancer

Presented By Martin Edelman at 2014 ASCO Annual Meeting

 HOSPITAL ALMENARA
• DOSAJE DE EFGR…….50 PACIENTES.
• POSITIVIDAD…………..12 PACIENTES.
24 % +

• ROS-1…..0
• ALK……….1

HOSP. ALMENARA
2014
Typical Responses to Crizotinib

Baseline After 3 months of crizotinib

ROS1-positive NSCLC

Bergethon et al., JCO 30(8): 863-70, 2012

ALK and ROS1 Encode Related
Receptor Tyrosine Kinases

ROS1

ROS1
ALK
LTK

PTK7

Brock TG, Receptors and Tyrosine Kinases

http://www.caymanchem.com/app/template/Article.vm/article/2187
Immunoterapia en cancer
de pulmon

• Inhibidores check- point.

• Vacunas.

Daniel S. Chen, Ira Mellman
Figure
Figure 2.
1. Stimulatory and Inhibitory
The Cancer-Immunity Factorsgeneration
CycleThe in the Cancer-Immunity
of immunity toCycleEach
cancer is astep of process
cyclic the
Cancer-Immunity Cycle requires
that can be self propagating, the coordination
leading of numerous
to an accumulation factors, both stimulatory
of immune-stimulatory factors and
that in
inhibitory in nature.
principle should Stimulatory
amplify factorsTshown
and broaden in green promote
cell responses. immunity,
The cycle is also ...where...
Oncology Meets Immunology: The
Cancer-Immunity Cycle
 Slide 5

Presented By Drew Pardoll at 2014 ASCO Annual Meeting

Imagen de un grupo de células T citotóxicas (verdes y rojas) que rodean una célula
cancerosa (azul, centro).
Crédito: Institutos Nacionales de la Salud /
PD-L1 (B7-H1) and PD-L2 (PD-1 ligands)

• PD-L1 and PD-L2 members of the B7 family of

transmembrane proteins
• PD-L1 is a 40 kDa protein with IgV-like and
IgC-like extracellular domains, and a
transmembrane domain, but no intracellular
signaling domain
• PD-L1 highly expressed in melanoma, ovarian
and NSCLC tumors
• Also expressed in myeloid cells of tumor
microenvironment
• PD-L2 is a 25 kDa protein with similar structure to
PD-L1 but expression is restricted to
cytokine-activated macrophages and DC
• PD-L2 upregulated in some B-cell lymphomas
 How to convert T cell poor tumors into <br />T cell inflamed tumors?

Presented By Laura Chow at 2014 ASCO Annual Meeting

 Effect in the CNS?

Presented By Laura Chow at 2014 ASCO Annual Meeting

 CA209-017

Nivolumab monotherapy as 2nd-line treatment:

progression-free survival
100
Nivoluma Docetaxel
90 b (n = 137)
(n = 135)
80
mPFS, mo 3.5 2.8
70 (95% CI) (2.1–4.9) (2.1–3.5)

60 HR = 0.62 (95% CI: 0.47–0.81); P <

0.001
PFS (%)

50

40

30 1-yr PFS rate = 21%

20
Nivolumab
10 1-yr PFS rate = 6%
Docetaxel
0
0 3 6 9 12 15 18 21 24
Time (months)
Number of Patients at Risk
Nivolumab 135 68 48 33 21 15 6 2 0
Docetaxel 137 62 26 9 6 2 1 0 0

PFS per investigator.

HR = hazard ratio; mPFS = median progression-free survival.
Brahmer J, et al. New Engl J Med. 2015;373:123-135.
 Conclusions

Presented By Laura Chow at 2014 ASCO Annual Meeting

 Vaccines for Lung Cancer

Presented By Drew Pardoll at 2014 ASCO Annual Meeting

 Potential Future of NSCLC - Molecular Profiling
Adenocarcinoma

EGFR mutation
Met + KRAS mutant
BRAF mutation PI3K mutant

EGFR TKI EML 4 ALK or ROS1 mutant

PI3K inhibitor
BRAF inhibitor
Met inhibition
Resistance – rebiopsy
T790M – irreversible EGFR crizotinib
TKI
MET upregulation – Met MEK inhibitor
Resistance – rebiopsy Resistance – rebiopsy
inhibitor combination
Novel agent Novel agent

Resistance – rebiopsy
Hsp90 inhibitor Resistance – rebiopsy
novel agent targeting ALK Novel agent
resistance mutation

Resistance – rebiopsy
Novel Agent

Platinum-doublet-bevacizumab
Platinum-pemetrexed + bevacizumab
Non-platinum or platinum based doublet
Switch Maintenance: pemetrexed, erlotinib
(E4599, AVAiL, Pointbreak, SATURN, JMEN)
 Immune Checkpoint Therapy:
What Is Next?
Anti–PD-1/PD-L1

Your favorite
treatment
The future
of cancer
therapy
 CheckMate 9LAa,b study design and analysis
population
• Stage
Key IV or recurrent
eligibility criteria NSCLC Analysis population (per
• No prior systemic therapy BICR)
• No sensitizing EGFR mutations or NIVO 360 mg Q3W + IPI 1 With Without
n = 361 mg/kg Q6W
known brain brain
ALK alterations +
metastases metastases
• ECOG PS 0–1 N = 719 chemod Q3W (2 at baseline at baseline
R NIVO + IPI NIVO + IPI
• Brain MRI/CT performed at baseline 1
cycles)
+ chemo + chemo
• For patients with brain metastases: : n = 310
n = 51
– Adequately treated and 1
asymptomatic for Chemod Q3W (4
≥ 2 weeks prior to first cycles) Chemo Chemo
c
treatment
Stratified bydose
PD-L1 (< 1% vs ≥ n = 358 with optional pemetrexed n = 50 n = 308
maintenance (NSQ)
1%), sex,
and histology (SQ vs NSQ)

Primary Secondary Post hoc analysis

endpoint endpoints • Systemice efficacy and safety in patients with or without brain
• PFS per BICR metastases at baseline
• OS
• ORR per BICR • Intracranialf efficacy in patients with brain metastases at
Database lock: February 18, 2021; minimum / median baseline
follow-up for OS: 24.4 months / 30.7 months
a b c
NCT03215706; Patients were treated until disease progression, unacceptable toxicity, or for 2 years for immunotherapy; Off corticosteroids, or on a stable or
decreasing dose of ≤ 10 mg daily prednisone (or equivalent) for ≥ 2 weeks before first treatment; dNSQ: pemetrexed + cisplatin or carboplatin; SQ: paclitaxel +
carboplatin; eSystemic efficacy was assessed by BICR per RECIST v1.1 criteria based on all lesions; fIntracranial efficacy was assessed by BICR per modified RECIST
v1.1 (adapted for brain metastases) based on brain lesions.
Gracias