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CP6: Improved radiotherapy and medical treatment Ditte Sloth Møller, Tine Schytte, Gitte Persson, Marianne Marquard Knap DOLGs Radioterapigruppe

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Page 1: CP6: Improved radiotherapy and medical treatment · CP6: Improved radiotherapy and medical treatment Ditte Sloth Møller, Tine Schytte, Gitte Persson, Marianne Marquard Knap DOLGs

CP6: Improved radiotherapy and medical treatment

Ditte Sloth Møller, Tine Schytte, Gitte Persson, Marianne Marquard Knap

DOLGs Radioterapigruppe

Page 2: CP6: Improved radiotherapy and medical treatment · CP6: Improved radiotherapy and medical treatment Ditte Sloth Møller, Tine Schytte, Gitte Persson, Marianne Marquard Knap DOLGs

Strålebehandling af lungekræft

Lokalt avancerede 700

SBRT 700

Palliativ 1000

Page 3: CP6: Improved radiotherapy and medical treatment · CP6: Improved radiotherapy and medical treatment Ditte Sloth Møller, Tine Schytte, Gitte Persson, Marianne Marquard Knap DOLGs

DOLG-RT

Lavstidium NSCLC

T1-T2 N0 M0

Onko-geriatrisk optimering ved SBRT

STAR LUNG Stereotaksi af centrale

lungetumorer og andre højrisiko lokalisationer

Lokalavanceret NSCLC T1-T4 N0-N3

M0

NARLAL 2 Fase III

FDG-PET baseret dosiseskalation

HERAN Fase II

Inhomogen hypofraktioneret RT til

store tumorer og patienter i PS 2

Modellering af RT- og responsevaluering

– en national retrospektiv

undersøgelse

Kardiotoksicitet efter RT

National retrospektiv analyse

Metastatisk NSCLC

M1a-M1c

PARAT Fase III

Pallierende thorakal RT

30Gy/10 vs 20Gy/4

SCLC begrænset

T1-T4 N0-N3

M0

Achilles Fase III konkomitant kemoradioterapi +/-

atezolizumab

Metastatisk SCLC

M1a-M1c

Ny protokol RT+immunterapi

Oligo metastaser

STAR LUNG Stereotaksi af centrale

lungetumorer og andre højrisiko lokalisationer

Page 4: CP6: Improved radiotherapy and medical treatment · CP6: Improved radiotherapy and medical treatment Ditte Sloth Møller, Tine Schytte, Gitte Persson, Marianne Marquard Knap DOLGs

DOLG-RT

Lavstidium NSCLC

T1-T2 N0 M0

Onko-geriatrisk optimering ved SBRT

STAR LUNG Stereotaksi af centrale

lungetumorer og andre højrisiko lokalisationer

Lokalavanceret NSCLC T1-T4 N0-N3

M0

NARLAL 2 Fase III

FDG-PET baseret dosiseskalation

HERAN Fase II

Inhomogen hypofraktioneret RT til

store tumorer og patienter i PS 2

Modellering af RT- og responsevaluering

– en national retrospektiv

undersøgelse

Kardiotoksicitet efter RT

National retrospektiv analyse

Metastatisk NSCLC

M1a-M1c

PARAT Fase III

Pallierende thorakal RT

30Gy/10 vs 20Gy/4

SCLC begrænset

T1-T4 N0-N3

M0

Achilles Fase III konkomitant kemoradioterapi +/-

atezolizumab

Metastatisk SCLC

M1a-M1c

Ny protokol RT+immunterapi

Oligo metastaser

STAR LUNG Stereotaksi af centrale

lungetumorer og andre højrisiko lokalisationer

Page 5: CP6: Improved radiotherapy and medical treatment · CP6: Improved radiotherapy and medical treatment Ditte Sloth Møller, Tine Schytte, Gitte Persson, Marianne Marquard Knap DOLGs

DOLG-RT

Lavstidium NSCLC

T1-T2 N0 M0

Onko-geriatrisk optimering ved SBRT

STAR LUNG Stereotaksi af centrale

lungetumorer og andre højrisiko lokalisationer

Lokalavanceret NSCLC T1-T4 N0-N3

M0

NARLAL 2 Fase III

FDG-PET baseret dosiseskalation

HERAN Fase II

Inhomogen hypofraktioneret RT til

store tumorer og patienter i PS 2

Modellering af RT- og responsevaluering

– en national retrospektiv

undersøgelse

Kardiotoksicitet efter RT

National retrospektiv analyse

Metastatisk NSCLC

M1a-M1c

PARAT Fase III

Pallierende thorakal RT

30Gy/10 vs 20Gy/4

SCLC begrænset

T1-T4 N0-N3

M0

Achilles Fase III konkomitant kemoradioterapi +/-

atezolizumab

Metastatisk SCLC

M1a-M1c

Ny protokol RT+immunterapi

Oligo metastaser

STAR LUNG Stereotaksi af centrale

lungetumorer og andre højrisiko lokalisationer

Page 6: CP6: Improved radiotherapy and medical treatment · CP6: Improved radiotherapy and medical treatment Ditte Sloth Møller, Tine Schytte, Gitte Persson, Marianne Marquard Knap DOLGs

Overlevelse stadium III NSCLC patienter på AUH Behandlet i 3 tidsperioder

Stadium III NSCLC

Adaptive RT 2013-17 (n=211) Median OS= 24 months 4DCT and IMRT 2010-13(n=139) Median OS= 19 months Before IMRT 2007-09 (n=84) Median OS= 15 months

Page 7: CP6: Improved radiotherapy and medical treatment · CP6: Improved radiotherapy and medical treatment Ditte Sloth Møller, Tine Schytte, Gitte Persson, Marianne Marquard Knap DOLGs

Calais J et. al. J Nucl Med. 2015; 56:196-203

PET aktivt før behandling Recidiv - 1 år efter

NSCLC recidiv

Page 8: CP6: Improved radiotherapy and medical treatment · CP6: Improved radiotherapy and medical treatment Ditte Sloth Møller, Tine Schytte, Gitte Persson, Marianne Marquard Knap DOLGs

Randomiseret fase 2

117 patienter

60 Gy vs 66 Gy

Oral Vinorelbine 3 gange / uge

66 Gy standard

behandling i Danmark

Hansen et al. Radioth Oncol. 2017;123:276-281

NARLAL1

Page 9: CP6: Improved radiotherapy and medical treatment · CP6: Improved radiotherapy and medical treatment Ditte Sloth Møller, Tine Schytte, Gitte Persson, Marianne Marquard Knap DOLGs

Bradley et al. The Lancet Oncology. 2015;16(2):187-199.

Randomiseret mellem 60 Gy og 74 Gy til hele target

RTOG 0617

Page 10: CP6: Improved radiotherapy and medical treatment · CP6: Improved radiotherapy and medical treatment Ditte Sloth Møller, Tine Schytte, Gitte Persson, Marianne Marquard Knap DOLGs

Standard dosis mulig

Homogen standard dosis

PTV: 66 Gy/33 fraktioner(F)

Heterogen, FDG-guided dosiseskalation

PET GTV-T ≤ 95 Gy/33 F (middel)

PET GTV-N ≤ 74 Gy/33 F (middel)

PTV: 66 Gy/33 F (min)

Heterogeneous FDG-guided dose-escalation for locally advanced NSCLC (the NARLAL2 trial): Design and early dosimetric results of a randomized, multi-centre phase-III study. Møller DS et al. Radiother Oncol. 124:311-317 (2017)

NARLAL2

Page 11: CP6: Improved radiotherapy and medical treatment · CP6: Improved radiotherapy and medical treatment Ditte Sloth Møller, Tine Schytte, Gitte Persson, Marianne Marquard Knap DOLGs

Primær tumor: 50% af SUV peak FDG-PET Eskalation op til: middel dosis 95 Gy /33 F

NARLAL2

Page 12: CP6: Improved radiotherapy and medical treatment · CP6: Improved radiotherapy and medical treatment Ditte Sloth Møller, Tine Schytte, Gitte Persson, Marianne Marquard Knap DOLGs

Primær tumor: 50% af SUV peak FDG-PET Eskalation op til: middel dosis 95 Gy /33 F Minimum dosis til PTV 66 Gy/33 F

NARLAL2

Page 13: CP6: Improved radiotherapy and medical treatment · CP6: Improved radiotherapy and medical treatment Ditte Sloth Møller, Tine Schytte, Gitte Persson, Marianne Marquard Knap DOLGs

Lymfeknuder større end 4 cm3: 50% of SUV peak Eskalation op til: middel dosis 74 Gy /33 F Minimum dose to PTV 66 Gy/33 F

Small lymph nodes – no escalation

NARLAL2

Page 14: CP6: Improved radiotherapy and medical treatment · CP6: Improved radiotherapy and medical treatment Ditte Sloth Møller, Tine Schytte, Gitte Persson, Marianne Marquard Knap DOLGs

Standard dosis mulig

Homogen standard dosis

PTV: 66 Gy/33 fraktioner(F)

Heterogen, FDG-guided dosiseskalation

PET GTV-T ≤ 95 Gy/33 F (middel)

PET GTV-N ≤ 74 Gy/33 F (middel)

PTV: 66 Gy/33 F (min)

Ens lunge dosis: MLD ± 1 Gy and V20Gy ± 2%.

Forskellig tumor dosisfordeling

Primært endepunkt: Lokoregional kontrol

NARLAL2

Stadium IIb – IIIb PS 0-1

Page 15: CP6: Improved radiotherapy and medical treatment · CP6: Improved radiotherapy and medical treatment Ditte Sloth Møller, Tine Schytte, Gitte Persson, Marianne Marquard Knap DOLGs

Durvalumab og NARLAL2

Page 16: CP6: Improved radiotherapy and medical treatment · CP6: Improved radiotherapy and medical treatment Ditte Sloth Møller, Tine Schytte, Gitte Persson, Marianne Marquard Knap DOLGs

Individualiseret RT

Nygård L et al. Competing Risk Model of First Failure Site after Definitive Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer. J Thorac Oncol. 2018;13(4):559-567.

Page 17: CP6: Improved radiotherapy and medical treatment · CP6: Improved radiotherapy and medical treatment Ditte Sloth Møller, Tine Schytte, Gitte Persson, Marianne Marquard Knap DOLGs

Individualiseret RT

Page 18: CP6: Improved radiotherapy and medical treatment · CP6: Improved radiotherapy and medical treatment Ditte Sloth Møller, Tine Schytte, Gitte Persson, Marianne Marquard Knap DOLGs

Teknologiske forbedringer

• Tumor tracking, behandling i DIBH

Page 19: CP6: Improved radiotherapy and medical treatment · CP6: Improved radiotherapy and medical treatment Ditte Sloth Møller, Tine Schytte, Gitte Persson, Marianne Marquard Knap DOLGs

Teknologiske forbedringer

• Tumor tracking, behandling i DIBH

Page 20: CP6: Improved radiotherapy and medical treatment · CP6: Improved radiotherapy and medical treatment Ditte Sloth Møller, Tine Schytte, Gitte Persson, Marianne Marquard Knap DOLGs

Teknologiske forbedringer – MR LINAC

• Tumor tracking med MR, behandling i DIBH

Courtesy Mirjana Josipovic og Mette Pøhl

Page 21: CP6: Improved radiotherapy and medical treatment · CP6: Improved radiotherapy and medical treatment Ditte Sloth Møller, Tine Schytte, Gitte Persson, Marianne Marquard Knap DOLGs

Teknologiske forbedringer – MR LINAC

• Tumor tracking med MR, behandling i DIBH

Courtesy Mirjana Josipovic og Mette Pøhl

Page 22: CP6: Improved radiotherapy and medical treatment · CP6: Improved radiotherapy and medical treatment Ditte Sloth Møller, Tine Schytte, Gitte Persson, Marianne Marquard Knap DOLGs

Teknologiske forbedringer - protonterapi

Photon Proton

Mean lung dose 12.3 Gy 7.2 Gy

Mean heart dose 10.1 Gy 2.1 Gy

Photons: 7F IMRT Protons: 3F IMPT

Page 23: CP6: Improved radiotherapy and medical treatment · CP6: Improved radiotherapy and medical treatment Ditte Sloth Møller, Tine Schytte, Gitte Persson, Marianne Marquard Knap DOLGs

DOLG-RT

Lavstidium NSCLC

T1-T2 N0 M0

Onko-geriatrisk optimering ved SBRT

STAR LUNG Stereotaksi af centrale

lungetumorer og andre højrisiko lokalisationer

Lokalavanceret NSCLC T1-T4 N0-N3

M0

NARLAL 2 Fase III

FDG-PET baseret dosiseskalation

HERAN Fase II

Inhomogen hypofraktioneret RT til

store tumorer og patienter i PS 2

Modellering af RT- og responsevaluering

– en national retrospektiv

undersøgelse

Kardiotoksicitet efter RT

National retrospektiv analyse

Metastatisk NSCLC

M1a-M1c

PARAT Fase III

Pallierende thorakal RT

30Gy/10 vs 20Gy/4

SCLC begrænset

T1-T4 N0-N3

M0

Achilles Fase III konkomitant kemoradioterapi +/-

atezolizumab

Metastatisk SCLC

M1a-M1c

Ny protokol RT+immunterapi

Oligo metastaser

STAR LUNG Stereotaksi af centrale

lungetumorer og andre højrisiko lokalisationer

Fælles ph.d studerende

opstart 2020

ph.d studerende Marie Tvilum startet 2019

ph.d. projekt Lotte Nygaard afsluttet 2019

ph.d studerende opstart 2020

Fælles post.doc