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Dr. Achmad Hudoyo, Sp.P (K) QUALIFICATIONS

1978 M.D., Fakultas Kedokteran Universitas Diponegoro, Semarang

1990 S2 Pulmonology. Fakultas Kedokteran Universitas Indonesia, Jakarta

1995 Thoracis & Mediastinum Oncology Consultant

2010 S3 Biomed Fak Kedokteran Universitas Indonesia

PRESENT APPOINTMENT

Medical Teaching staff member, Departemen Pulmonologi dan Ilmu Kedokteran Respirasi

FKUI/SMF Paru Persahabatan, Jakarta

Spesialis paru konsultan RS Pondok Indah

ADDITIONAL TRAINING 1. Overseas Technical Training in Kobe, Japan

2. Training Penatalaksanaan Penyakit Paru Interstisial dan Onkologi Paru di Toranomon Hospital dan

National Cancer Center, Tokyo, Japan

Overview of lung cancer in Indonesia

Dr. dr. Achmad Hudoyo, SpP (K) Dept of Pulmonology & Respiratory

Medicine Faculty of Medicine-Universitas Indonesia

RSUP Persahabatan

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• 1. EPIDEMIOLOGI

• 2. SKRINING KANKER PARU

• 3. KETERLAMBATAN DIAGNOSIS

• 4. OPTIMALISASI PEMERIKSAAN SITOLOGI

• 5. INOVASI DIAGNOSTIK NON-INVASIF

• 6. “REVOLUSI” DALAM PENGOBATAN KANKER PARU

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Lung Cancer in World wide : High incidence, highest mortality rate

Globocan 2018, http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf access on 4 March 2019

http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdfhttp://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdfhttp://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdfhttp://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdfhttp://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdfhttp://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdfhttp://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdfhttp://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf

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Lung Cancer in Indonesia :

High Incidence (Top 3), high mortality rate (1st Rank)

Globocan 2018, http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf access on 4 March 2019

http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdfhttp://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdfhttp://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdfhttp://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdfhttp://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdfhttp://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdfhttp://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf

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Lung Cancer in Indonesia :

The incidence in males is higher than females

Globocan 2018, http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf access on 4 March 2019

http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdfhttp://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdfhttp://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdfhttp://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdfhttp://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdfhttp://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdfhttp://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdfhttp://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf

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Kristina SA, et al. Burden of Cancers Related to Smoking among the Indonesian Population: Premature Mortality Costs and Years of Potential Life Lost. Asian Pac J Cancer

Prev. 2015;16(16):6903-8.

• Lung cancer mortality

costs caused by

smoking accounted for

USD 621 million in

2013. Among all

cancers, lung cancer

is the leading cause of

death and economic

burden

• Smoking is proven as

major risk factors for

lung cancer

• Indonesia is a major

smoking country in the

world

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Indonesia is a major smoking country in South East Asia

The World Bank data 2016 , https://data.worldbank.org/indicator/SH.PRV.SMOK?contextual=region&locations=ID&name_desc=false accessed on 4 March 2019

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Indonesian Lung cancer patients life expectancy Data from RSUD Moewardi, Solo presented in WCLC Yokohama 2017 • 105 patients, cohort retrospective

• One year survival rate: 38.1%

• Median survival at 205 days (6-7 bulan)

• Most patients come with pleural effusion (1 year survival rate of 26.7%)

• Survival female patients (60% survival rate, median 365 days) are higher than male patients (31.2% survival rate, median 200 days)

• Adenocarcinoma has better one year survival because 20% get targeted therapy

– 1 year survival of targeted therapy is 88.9% and median survival is 365 days

• Factors affecting one year survival are gender, histology type, performance status, type of management and pleural effusion

• Age and smoking has no correlation

Ana Rima et al., presented at poster session, WCLC Yokohama 2017

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54% of first referral came to Pumonologists and mode of investigations vary between specialists

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Lung Cancer Screening: Recommendation from ACS 2018

Cancer Site Population Test or Procedure Recommendation

Lung

Current or former smokers aged

55-74 y/o in good health with at

least a 30 pack-year history of

smoking

Low dose helical CT (LDCT)

Annual screening in adults who:

• Currently smoke or have quit

within the past 15 years; and

• Have at least a 30 pack year

smoking history; and

• Receive evidence based

smoking cessation

counseling, if they are current

smokers; and

• Have undergone a process of

informed/shared decision

making that included

information about the

potential benefits, limitations,

and harms of screening with

low dose CT; and

• Have access to a high

volume, high quality lung

cancer screening and

treatment center

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What’s Next in Screening?

Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Consortium for Early Detection of Lung Cancer. Assessment of Lung Cancer Risk on the Basis of a

Biomarker Panel of Circulating Proteins. JAMA Oncol. Published online July 12, 2018. doi:10.1001/jamaoncol.2018.2078

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• Cancer antigen 125 [CA125]

• Carcinoembryonic antigen

[CEA]

• Cytokeratin-19 fragment

[CYFRA 21-1]

• Precursor form of

surfactant protein B [Pro-

SFTPB]

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Mirip TB Milier

- Beda : milier rata

- Kasus : ada massa

- Umur : dewasa/tua

- TB milier demam

- TB milier : tdk batuk

- EVALUASI (?)

STUDI KASUS 1

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Beda dg Efusi pl TB

- TB : demam (+)>>

- Efusi TB : tdk nyeri

- Umur : > dewasa

- Respon OAT : cepat

(efusi : tidak

berulang)

- EVALUSI (?)

STUDI KASUS 2

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!!! Umur (59 th) : tidak muda

- Bukan Infiltrat

- Tidak ada Kavitas

- Tidak ada Kalsifikasi

- Bukan Fibrosis

(corakan vaskular)

- Tidak ada respon OAT

- EVALUASI (?)

STUDI KASUS 3

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More innovative non-invasive way to detect lung cancer being researched

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More innovative non-invasive way to detect lung cancer being researched

KARSINOGENESIS

Faktor Lingkungan*

Faktor Internal (Diet)

Perubahan genetik Ireversibel -Mutasi DNA : (+)

Perubahan epigenetik Reversibel Mutasi DNA : (-)

Suseptibilitas genetik

Kelainan ekspresi gen

KANKER

PARU *Faktor lingkungan : - Asap rokok (85%) - Bahan radioaktif - Zat kimia industri - Polusi udara - Virus, tuberkulosis,PPOK

EBC (Exhale Breath Condensate)

VOC(Volatile Organic Compound)

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Pelatihan Anjing untuk deteksi kanker paru : perlu waktu antara 2 bulan – 9 bulan

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Prototipe alat penampung uap nafas yang telah dibuat dan digunakan

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Prototipe

1 2

3

4 5 6

7

8 9

10

11

12

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Analisis metilasi DNA

Digunakan metode MSP (Methylated Spesific Primer)

DNA hasil isolasi dilakukan konversi bisulfit kemudian dianalisis menggunakan

pet primer spesifik metil – unmetil

Kontrol keberhasilan proses konversi bisulfit digunakan gen MYOD1

The MYOD1 promoter contains no CpG islands, and therefore all cytosine is converted to uracil by bisulfite treatment.Thus, this primer binds only to modified DNA (the DNA that was not successfully modified failed to show PCR products with MYOD1 primer). (Zhang, et all, 2007)

M NTC BT HM 1 2 3 4 D1 D2 S1 S2 M

Gambar Hasil analisis gel elektroforesis amplifikasi gen MYOD1

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M NTC BT HM 1 2 3

U M U M U M U M U M U M

M NTC BT HM 1 2 3

U M U M U M U M U M U M

M 4 D1 D2 S1 S2

U M U M U M U M U M

M 4 D1 D2 S1 S2

U M U M U M U M U M

Gambar Hasil analisis MSP pada promotor gen APC Gambar Hasil analisis MSP pada promotor gen RASSF1A

U= produk PCR unmethylated primer set M= produk PCR methylated primer set control unmet: sel line BT (Breast Tumor) met: HM (DNA Human Methylated)

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Penentuan jenis senyawa berdasarkan pendekatan pola fragmentasi senyawa dalam sampel dengan pola fragmentasi senyawa database library willey9N11.L

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GCMS, merk AGILENT

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Yang dipilih

Yang dipilih

Gambar pencarian senyawa berdasarkan database

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Persentase Senyawa

Grafik senyawa Spesifik pasien kanker paru

2-metil-pentana

dimethylhydrazon-e-pentanone

2-propanamine

2-butanone

methyl-benzena

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Conclusion

• Lung Cancer in Indonesia is one of country’s major health problem, with high mortality rate

• Most patients made it into clinic of pulmonologist late and diagnosed above stage IIIA. Early screening must be done to get patients early in their course of disease

• There are multiple innovative screening method available:

– 4 Biomarkers: CRP, Prolactin, HGF and NY-ESO-1 autoantibody

– Another 2018 update on molecular markers: CA-125, CEA, CYFRA 21-1, Pro-SFTPB (Pro Surfactant Protein B)

– Breath DNA Analyzer

– Urine DNA Analyzer

• Screening and curative treatment (early intervention) carry best cost effective method with least probability transition to death

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Approved in :

FDA

EMA

BPOM*

* 1st line & BPJS (?)

Erlotinib is proven: multiple successful clinical trials and

experience in over 300,000 patients worldwide

Male 65 yo with BAC*, received !st line EGFR-Tki

*BAC : Bronchiolo Alveolar Carcinoma ((One of The-Predictive Factors)

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Subjective Response > Objective Response

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F 68 th

Nov 11-2011 : “betuk2-kecil”

Des 12-2011 fnab : AdenoCa (Sgpr)

R/ Gefitinib (Iressa) : 1 x 250 mg

R/ Erlotinib (Tarceva) : 1 x 150 mg

R/ Afatinib 40 mg (“paronychia” & stomatitis)

R/ Afatinib (Giotrif): 1 x 30 mg

R/ Afatinib 30 mg + Cetuximab (Erbitux) 300 mg

R/ Afatinib 30 mg + Nimotuzumab (TheraCim) 200 mg

(Oct 15-2014) PS : 0-1/90 SK

Rekomendasi (biopsi ulang) Foundation-One (USA)*

R/ Pembrolizumab (Keytruda) : 10 x/ bulan

R/ Osimertinib (Tagrisso)

HUT 74 : Wafat

(6 th berjuang)!

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Conclusion

• Lung Cancer in Indonesia is one of country’s major health problem, with high mortality rate

• Most patients made it into clinic of pulmonologist late and diagnosed above stage IIIA. Early screening must be done to get patients early in their course of disease

• There are multiple innovative screening method available:

– 4 Biomarkers: CRP, Prolactin, HGF and NY-ESO-1 autoantibody

– Another 2018 update on molecular markers: CA-125, CEA, CYFRA 21-1, Pro-SFTPB (Pro Surfactant Protein B)

– Breath DNA Analyzer

– Urine DNA Analyzer

• Screening and curative treatment (early intervention) carry best cost effective method with least probability transition to death

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