1  

Lung  Cancer:  Radiotherapy      ESO-­‐ESMO  La*n-­‐America  2018    Talented  students…  colleagues    

Selected  topics  for  talented…  •  Bio-­‐IGRT…PET/CT  planning  •  A  flavour  of  NCCN  -­‐  RT  -­‐  NSCLL  •  NSCLC…RT  by  stages  •  SCLC…RT  LD  vs  ED  •           Oligo  M1  

2  

A  bad  enemy…  or  not  so…  

Mortality…  

The RT nodal nightmare…

conebeam  CT  +  respiratory  gai*ng  +  VMAT  

multiple closed targets = VMAT high gradient dose-deposit

non-­‐coplanar  fields  

 morfology    functional    Multimodal  imaging  

PET/CT  impact   total   NSCLC   SCLC  Changes  target  definiBon   36%   43%   26%  Treatment-­‐intent  (c  to  p)   20%   22%   9%  

PET/CT  dose  planning  !  (2/5;  1/5  paBents  need  a  change)  

Selected  topics  for  talented…  •  Bio-­‐IGRT…PET/CT  planning  •  A  flavour  of  NCCN  -­‐  RT  -­‐  NSCLL  •  NSCLC…RT  by  stages  •  SCLC…RT  LD  vs  ED  •           Oligo  M1  

11  

NCCN Guidelines Index NSCLC TOC  Discussion NCCN Guidelines Version 4.2016 Non-Small Cell Lung Cancer NCCN Evidence BlocksTM

jPositive PET/CT scan findings for distant disease need pathologic or other radiologic confirmation. If PET/CT scan is positive in the mediastinum, lymph node status needs pathologic confirmation.  kSee Principles of Surgical Therapy (NSCL-B). lSee Principles of Radiation Therapy (NSCL-C).  nAfter surgical evaluation, patients likely to receive adjuvant chemotherapy may be

oSee Chemotherapy Regimens for Neoadjuvant and Adjuvant Therapy (NSCL-D). qSee Chemotherapy Regimens Used with Radiation Therapy (NSCL-E).  rR0 = no residual tumor, R1 = microscopic residual tumor, R2 = macroscopic residual tumor.

MEDIASTINAL BIOPSY FINDINGS INITIAL TREATMENT ADJUVANT TREATMENT    See NSCL-3 T1-3, N0-1  (including T3 with multiple nodules in same lobe)

Surgeryk,n Resectable

Medically inoperable

Surgical resectionk  + mediastinal lymph node dissection or systematic lymph node sampling

chemoradiationl,q (NSCL-14)

T1-2, T3  (other than invasive), N2 nodes positivei

• Brain MRI with contrast  • FDG PET/CT  scan,j if not previously done

See Treatment according to clinical stage (NSCL-2)    Definitive concurrent  chemoradiationl,q

N0–1

N2 Margins negative (R0)r Sequential chemotherapyo (category 1) + RTl    Chemoradiationl Margins positive

Surveillance (NSCL-14) R1r

R2r (sequential or concurrent ) Concurrent

o q Surveillance (NSCL-14) Surveillance

Negative for M1 disease

Positive

(category 1) or Induction  chemotherapyo ± RTl Progression    See Treatment for Metastasis limited sites (NSCL-13) or distant disease (NSCL-15)    Definitive concurrent  chemoradiationl,q

Surgeryk ± chemotherapyo (category 2B)  ± RTl (if not given)    RTl (if not given) ± chemotherapyo    See Treatment for Metastasis limited sites (NSCL-13) or distant disease (NSCL-15)

No apparent progression Local Systemic

T3  (invasion), N2 nodes positive

Negative for M1 disease

Positive See Treatment for Metastasis limited sites (NSCL-13) or distant disease (NSCL-15)

• Brain MRI with contrast  • FDG PET/CT  scan,j if not previously done

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treated with induction chemotherapy as an alternative.     Note: For more information regarding the categories and definitions used for the NCCN Evidence BlocksTM, see page EB-1. Note: All recommendations are category 2A unless otherwise indicated.  Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. NSCL-8 Version 4.2016, 02/29/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Evidence BlocksTM, NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

NCCN Guidelines Index NSCLC TOC  Discussion NCCN Guidelines Version 4.2016 Non-Small Cell Lung Cancer NCCN Evidence BlocksTM

hMethods for evaluation include mediastinoscopy, mediastinotomy, EBUS, EUS, and CT-guided biopsy.  jPositive PET/CT scan findings for distant disease need pathologic or other radiologic confirmation. If PET/CT scan is positive in the mediastinum, lymph node status needs pathologic confirmation. kSee Principles of Surgical Therapy (NSCL-B). lSee Principles of Radiation Therapy (NSCL-C). oSee Chemotherapy Regimens for Neoadjuvant and Adjuvant Therapy (NSCL-D).

rR0 = no residual tumor, R1 = microscopic residual tumor, R2 = macroscopic residual tumor.  wLesions with different cell types (eg, squamous cell carcinoma, adenocarcinoma) may be different primary tumors. This analysis may be limited by small biopsy samples. However, lesions of the same cell type are not necessarily metastases. xFor guidance regarding the evaluation, workup, and management of subsolid pulmonary nodules, please see the diagnostic evaluation of a nodule suspicious for lung cancer (DIAG-1).

CLINICAL PRESENTATION ADJUVANT TREATMENT Separate pulmonary nodule(s), same lobe (T3, N0-1), or  ipsilateral non-primary lobe (T4, N0-1)

Stage IV (N0, M1a): Contralateral lung (solitary nodule) Suspected multiple lung cancers (based on the presence of biopsy- proven synchronous lesions or history of lung cancer)w,x

Surgeryk

Treat as two primary lung tumors if both curable • Chest CT with contrast  • FDG PET/CT scan (if not previously done)j  • Brain MRI with contrast

N0–1

N2

Chemotherapyo Surveillance (NSCL-14)    Surveillance (NSCL-14) Margins negative (R0)r

Margins positive

Sequential chemotherapyo (category 1) + RTl

R1r

R2r

Chemoradiationl (sequential or concurrent ) o q Concurrent chemoradiationl,q

Surveillance (NSCL-14) Surveillance (NSCL-14)

See Evaluation (NSCL-1) Disease outs ide of chest No disease outside of chest

See Systemic Therapy for Metastatic Disease (NSCL-16)

Pathologic mediastinal lymph node evaluationh N2-3

N0-1 See Systemic Therapy for Metastatic Disease (NSCL-16)

See Initial Treatment (NSCL-10)

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qSee Chemotherapy Regimens Used with Radiation Therapy (NSCL-E).     Note: For more information regarding the categories and definitions used for the NCCN Evidence BlocksTM, see page EB-1. Note: All recommendations are category 2A unless otherwise indicated.  Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. NSCL-9 Version 4.2016, 02/29/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Evidence BlocksTM, NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

Selected  topics  for  talented…  •  Bio-­‐IGRT…PET/CT  planning  •  A  flavour  of  NCCN  -­‐  RT  -­‐  NSCLL  •  NSCLC…RT  by  stages  •  I  SBRT  •  II  •  III  CRT  /  PCI  /  AFxT  •  PORT:  CT  +  RT  vs  RT  •  SCLC…RT  LD  vs  ED  •  Oligo  M1  

14  

NSCLC Stage I

 Stage  I  •  20%    NSCLC  stage  I  

•   60-­‐70%  OS  5y    (including  RT  )    •  SBRT  as  an  alterna*ve  

•  20%  stage  I  are  inoperables    

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)

Non-Small Cell Lung Cancer!

NCCN Evidence Blocks™    

Version 4.2016       NCCN.org

Version 4.2016, 02/29/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Evidence BlocksTM, NCCN Guidelines®, and this illustration may not be reproduced in any form without the express written permission of NCCN®.

Continue!

NCCN Guidelines Index NSCLC TOC  Discussion NCCN Guidelines Version 4.2016 Non-Small Cell Lung Cancer NCCN Evidence BlocksTM

eT3, N0 related to size or satellite nodules.  gTesting is not listed in order of priority and is dependent upon clinical circumstances, institutional processes, and judicious use of resources. hMethods for evaluation include mediastinoscopy, mediastinotomy, EBUS, EUS, and CT-guided biopsy.  iSolid tumors <1 cm and purely non-solid tumors <3 cm that are CT and PET negative have a low likelihood of positive mediastinal lymph nodes and pre- resection pathologic mediastinal evaluation is optional.  jPositive PET/CT scan findings for distant disease need pathologic or other radiologic confirmation. If PET/CT scan is positive in the mediastinum, lymph node status needs pathologic confirmation.  kSee Principles of Surgical Therapy (NSCL-B).

lSee Principles of Radiation Therapy (NSCL-C). mInterventional radiology ablation is an option for selected patients.  nAfter surgical evaluation, patients likely to receive adjuvant chemotherapy may be treated with induction chemotherapy as an alternative. oSee Chemotherapy Regimens for Neoadjuvant and Adjuvant Therapy (NSCL-D). pExamples of high-risk factors may include poorly differentiated tumors (including lung neuroendocrine tumors [excluding well-differentiated neuroendocrine tumors]), vascular invasion, wedge resection, tumors >4 cm, visceral pleural involvement,  and incomplete lymph node sampling (Nx). These factors independently may not be an indication and may be considered when determining treatment with adjuvant chemotherapy. qSee Chemotherapy Regimens Used with Radiation Therapy (NSCL-E).

CLINICAL ASSESSMENT PRETREATMENT EVALUATIONg INITIAL TREATMENT

Stage IA  (peripheral T1ab, N0)

Stage IB (peripheral T2a, N0)  Stage I  (central T1ab–T2a, N0)  Stage II  (T1ab–2ab, N1; T2b, N0)  Stage IIB (T3, N0)e Stage IIIA (T3, N1)

• PFTs (if not previously done)  • Bronchoscopy (intraoperative preferred)  • Pathologic mediastinal lymph node evaluationh,i  • FDG PET/CT scanj (if not previously done)

• PFTs (if not previously done)  • Bronchoscopy  • Pathologic mediastinal lymph node evaluationh  • FDG PET/CT scanj (if not previously done)  • Brain MRI with contrast (Stage II, IIIA  Stage IB [category 2B])

Negative mediastinal nodes Positive mediastinal nodes

Operable Medically inoperablek

Negative mediastinal nodes

Positive mediastinal nodes

Operable

Medically   k inoperable

Surgical exploration and resectionk + mediastinal lymph node dissection or systematic lymph node sampling Definitive RT including stereotactic  ablative radiotherapyl (SABR)m See Stage IIIA (NSCL-7) or Stage IIIB (NSCL-11) Surgical exploration and resectionk,n + mediastinal lymph node dissection or systematic lymph node sampling N0 N1 Definitive chemoradiationl,q See Stage IIIA (NSCL-7) or Stage IIIB (NSCL-11)

Definitive  RT including SABR l

See Adjuvant Treatment (NSCL-3)

See Adjuvant Treatment (NSCL-3) Consider adjuvant chemotherapy (category 2B) for high- risk stages IB-IIIAp

o

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Note: For more information regarding the categories and definitions used for the NCCN Evidence BlocksTM, see page EB-1. Note: All recommendations are category 2A unless otherwise indicated.  Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. NSCL-2 Version 4.2016, 02/29/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Evidence BlocksTM, NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

SBRT  Stereotactic Body Radiation Therapy SABR  Stereotactic Ablative Radiation Therapy

60 Gy (80%) 60 Gy (60%)

PTV X 60 Gy

Older RT PTV X 75 Gy

PTV X 100 Gy

SABR

57 Gy

Senan, Palma, Lagerwaard, J Thorac Dis 2011

60  Gy  in  3  differents  ways…  

Senthi et al Lancet Oncology 2012

5 yr LC 89.5% 5 yr RC 87.3% 5 yr DC 80.1%

@  3  years  aYer  SBRT  

60 Gy /8 Fx 60 Gy/3 Fx            •  Meta-analysis (Senthi 2012):  •  BED10 ≥ 100 to maximize local control  •  BED3 ≤ 240 to keep risk of fatal toxicity to 1%.

Centrality…  

Timmerman et al JCO 2006 Haasbeek et al JTO 2011

RTOG 0813: ASTRO 2015

•  Several population-based studies suggest SABR better for OS:  •  Palma, Amsterdam Cancer Registry, JCO 2010  •  Haasbeek, Netherlands Cancer Registry, Annals of Oncology 2011  •  Shirvani, SEER-Medicare, IJROBP 2012  

•  At least 3 RCTs launched comparing SABR with standard or less-  hypofractionated regimens    •  SPACE (Sweden) – completed, abstract available  •  CHISEL (Australia) – completed, maturing  •  LUSTRE (Canada)

SABR vs. older techniques

SABR  could  be  an  op*on  for  trea*ng  operable  stage  I  NSCLC.  Because  of  the  small  pa*ent  sample  size  and  short  follow-­‐up,  addi*onal  randomised  studies  comparing  SABR  with  surgery  in  operable  pa*ents  are  warranted.  metastases

regional

local

Stage  I  Peripheral  Non-­‐Small  Cell  Lung  Cancer:    NRG  Oncology  RTOG  0915  (NCCTG  N0927).  Int  J  Radiat  Oncol  Biol  Phys.  2015  Nov  15;93(4):757-­‐64  

98  pts    Extreme  fracBonaBon  1  fx!      34  Gy    (1fx)  vs  48  (4fx)  =  97%  vs  91%  primary  control  (1y)  

SBRT    (Stereotac)c  Body  Radia)on  Therapy):  technologies  

cone-beam CT + VMAT volumetric arc therapy

SBRT  vs  Surgery  

SBRT  in  central  loca)ons  

SBRT    “centrals”  

event  /  outcome   SABRT   Non-­‐SABRT  pneumoni*s   11%   13%  Treatment-­‐related  deaths   <  1%   1,1%  @2  y  ms   71  months   47  months  @3y  ms   60  months   38  months  Median  OS   37  months   17  months  

SABRT  

Non-­‐SABRT  

OS  @  5y  

CSS  @  5y  

Meta-­‐analyses  of  current  evidence  suggested  that  lobectomy  provides  beber  long-­‐term  survival  outcomes  for  stage  I  NSCLC  pa*ents.  

•  15  publica*ons    315  pa*ents  •  loca*on  (central  v  peripheral)  does  not  influence    survival    •  local  control  (3yr-­‐DFS)  ≥  85%  with  doses  BED  ≥  100  Gy10  •  mortality  ≤  1%  with  BED≤  210  Gy3  •  ↑toxicity  G  3-­‐4  in    central  tumors,  but  <  9%  

SBRT    thoracic  central  sites  

   NSCLC    stage  II  

NCCN Guidelines Index NSCLC TOC  Discussion NCCN Guidelines Version 4.2016 Non-Small Cell Lung Cancer NCCN Evidence BlocksTM

lSee Principles of Radiation Therapy (NSCL-C). oSee Chemotherapy Regimens for Neoadjuvant and Adjuvant Therapy (NSCL-D). pExamples of high-risk factors may include poorly differentiated tumors (including lung neuroendocrine tumors [excluding well-differentiated neuroendocrine tumors]), vascular invasion, wedge resection, tumors >4 cm, visceral pleural involvement, and incomplete lymph node sampling (Nx). These factors independently may not  be an indication and may be considered when determining treatment with adjuvant chemotherapy.

qSee Chemotherapy Regimens Used with Radiation Therapy (NSCL-E). rR0 = no residual tumor, R1 = microscopic residual tumor, R2 = macroscopic residual tumor.  sIncreasing size is an important variable when evaluating the need for adjuvant chemotherapy.

FINDINGS AT SURGERY ADJUVANT TREATMENT Stage IA (T1ab, N0) Margins negative (R0)r

Margins positive (R1, R2)r Observe Reresection (preferred) or  RTl (category 2B)

Surveillance (NSCL-14)

Stage IB (T2a, N0);  Stage IIA (T2b, N0)

Stage IIA (T1ab-T2a, N1)  Stage IIB (T3, N0; T2b, N1)

Stage IIIA (T1-3, N2; T3, N1)

Margins negative (R0)r

Margins positive (R1, R2)r Margins negative (R0)r

Margins positive R1r

R2r

Margins negative (R0)r

Margins positive R1r R2r

Observe or  Chemotherapyo for high-risk patientsp Reresection (preferred) ± chemotherapyo,s or  RTl ± chemotherapyo (chemotherapy for stage IIA) Chemotherapyo (category 1) Reresection + chemotherapyo or  Chemoradiationl,q (sequential or concurrent) Reresection + chemotherapyo or  Concurrent chemoradiationl,q Chemotherapyo (category 1) or  Sequential chemotherapyq + RTl (N2 only) Chemoradiationl,q (sequential or concurrent) Concurrent chemoradiationl,q

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Note: For more information regarding the categories and definitions used for the NCCN Evidence BlocksTM, see page EB-1. Note: All recommendations are category 2A unless otherwise indicated.  Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. NSCL-3 Version 4.2016, 02/29/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Evidence BlocksTM, NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

   NSCLC    stage  III  

 10  retrospec*ve  studies  5  (12,896  pa*ents)  OS    4  (981  pa*ents)  radia)on  pneumoni)s    4  (1339  pa*ents)  radia)on  oesophagi)s    3DCRT  and  IMRT  similar  OS  (HR=0.96,P=0.477)  IMRT  reduced  grade2  radia'on  pneumoni's  (RR=0.74,P=0.009)  IMRT  increased  grade3  radia'on  oesophagi's  (RR=2.47,P=0.000)  

OS  

low-­‐dose  RT  +  Lager  T  &  N  +  cord  +  lung  constrains    ???  

CRT superior

RT combination with CT and / or bioagents

NCCN Guidelines Index NSCLC TOC  Discussion NCCN Guidelines Version 4.2016 Non-Small Cell Lung Cancer NCCN Evidence BlocksTM

kSee Principles of Surgical Therapy (NSCL-B). lSee Principles of Radiation Therapy (NSCL-C). oSee Chemotherapy Regimens for Neoadjuvant and Adjuvant Therapy (NSCL-D). tRT should continue to definitive dose without interruption if patient is not a surgical candidate.  uIf full-dose chemotherapy is not given concurrently with RT as initial treatment, give

CLINICAL PRESENTATION INITIAL TREATMENT ADJUVANT TREATMENT Superior sulcus tumor (T3 invasion, N0-1)

Superior sulcus tumor (T4 extension, N0-1)

Preoperative concurrent chemoradiationl,q

Possibly resectablek

Unresectablek

Preoperative concurrent chemoradiationl,q

Definitive concurrent  chemoradiationl,q,t,u

Surgical reevaluation Resectable

Unresectable

Surgeryk + chemotherapyo Surveillance (NSCL-14)

Surgeryk + chemotherapyo

Complete definitive RTl + chemotherapyq

Surveillance (NSCL-14) Surveillance (NSCL-14)

Surveillance (NSCL-14)

qSee Chemotherapy Regimens Used with Radiation Therapy (NSCL-E). additional 2 cycles of full-dose chemotherapy. Note: For more information regarding the categories and definitions used for the NCCN Evidence BlocksTM, see page EB-1. Note: All recommendations are category 2A unless otherwise indicated.  Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. NSCL-5 Version 4.2016, 02/29/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Evidence BlocksTM, NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

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NCCN Guidelines Index NSCLC TOC  Discussion NCCN Guidelines Version 4.2016 Non-Small Cell Lung Cancer NCCN Evidence BlocksTM

kSee Principles of Surgical Therapy (NSCL-B). lSee Principles of Radiation Therapy (NSCL-C). oSee Chemotherapy Regimens for Neoadjuvant and Adjuvant Therapy (NSCL-D). qSee Chemotherapy Regimens Used with Radiation Therapy (NSCL-E). rR0 = no residual tumor, R1 = microscopic residual tumor, R2 = macroscopic

tRT should continue to definitive dose without interruption if patient is not a surgical candidate.  uIf full-dose chemotherapy is not given concurrently with RT as initial treatment, give additional 2 cycles of full-dose chemotherapy.  vConsider RT boost if chemoradiation is given as initial treatment.

CLINICAL PRESENTATION INITIAL TREATMENT ADJUVANT TREATMENT

Chest wall, proximal airway, or mediastinum  (T3 invasion, N0-1 Resectable T4 extension, N0-1)

Stage IIIA (T4, N0-1)  Unresectable

Surgeryk (preferred)

or

Concurrent chemoradiationl,q or Chemotherapyo

Margins negative (R0)r

Margins positive

Definitive concurrent  chemoradiationl,q,t,u (category 1)

Surgeryk

R1r

R2r

Margins negative (R0)r

Margins positive (R1, R2)r

Chemotherapyo Reresection + chemotherapyo or  Chemoradiationl,q (sequential or concurrent)    Reresection + chemotherapyo or  Concurrent chemoradiationl,q

Observe

Reresectionv

Surveillance (NSCL-14) Surveillance (NSCL-14) Surveillance (NSCL-14) Surveillance (NSCL-14)

Surveillance (NSCL-14) Surveillance (NSCL-14)

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residual tumor.     Note: For more information regarding the categories and definitions used for the NCCN Evidence BlocksTM, see page EB-1. Note: All recommendations are category 2A unless otherwise indicated.  Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. NSCL-6 Version 4.2016, 02/29/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Evidence BlocksTM, NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

   stage  III  

•   heterogeneus  group:  ~  resectability,  medias*num  bulky  (>2-­‐3  cm  Ø  short,  mul*ple  gg  gruped,  >  2  sta*ons)  ,  staging  methods  (imaging  CT/PET,  invasive),  TNM  categories  

s  III:    RT  dose  •  RTOG-­‐7301              60  Gy  improved  LC  

•  RTOG-­‐0617              74  Gy    inferior  to  60  Gy  (↔  cardiac  dose  contribu*on  ?)  25 years of practice…

74  Gy  radia*on  given  in  2  Gy  frac*ons  with  concurrent  chemotherapy  was  not  beber  than  60  Gy  plus  concurrent  chemotherapy  for  pa*ents  with  stage  III  non-­‐small-­‐cell  lung  cancer,  and  might  be  potenBally  harmful.  Addi*on  of  cetuximab  to  concurrent  chemoradia*on  and  consolida*on  treatment  provided  no  benefit  in  overall  survival  for  these  pa*ents.    

RTOG 0617 - PRO resultados

•  3D vs IMRT and quality of life  •  Not randomized  •  IMRT less QOL deterioration although

treating more extensive volumes!

RTOG 0617 - intra - story

s  III:    nodal  elec)ve  RT  •  <  7-­‐10%  relapses  in  gg  not  involved  and  even  less  with  PET  guided  RT  

•   High  doses    on  small  volumen  (new  paradigm)  

PET-­‐TAC  FUSION   CONEBEAM  VERIFICATION  

FUSION PET-TAC

CONE BEAM

RC  by  PET-­‐TAC  

Lung  and  nodal  SBRT  

Results:    3  RCTs  and  3  cohort  studies    -­‐  No  difference  in  ELECTIVE  NODAL  FAILURE:    IFRT  and  ENI  among  RCTs  (  p=0.46),  cohort  studies  (p=0.97)  or  combined  (p=0.64).      Conclusion:  This  meta-­‐analysis  provides  evidence  of  no  significant  difference  in  incidence  of  ENF  between  IFRT  and  ENI.  

s  III:  PCI      no  effect  on  OS  (RTOG  0214)  

 EORTC  QLQ-­‐C30  significant  decline  self  reported  cogni*ve  func*on    Hopkins  verbal  learning  test  

 Int  J  Radiat  Oncol  Biol  Phys  2013  

PCI  sIII  NSCLC  Meta-analysis PlosOne 2014 12 trial (6 RCTs) 1,718 NSCLC pts reduced risk of brain mets p = 0.00001 OS favored non-PCI p = 0.004

Lancet. 2016 Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial.

Whole brain RT questionable for non-S-RS candidates

Survival

Quality of life

QUALYs

   NSCLC    Altered  Frac*ona*ons  

•  meta-analysis individual data   (Mauguen et al,2012: 12 ECCC - 2685 pts)

OS @ 5y 8.8% vs 10.5%

NSCLC  

NSCLC  

NCCN Guidelines Index NSCLC TOC  Discussion NCCN Guidelines Version 4.2016 Non-Small Cell Lung Cancer NCCN Evidence BlocksTM

jPositive PET/CT scan findings for distant disease need pathologic or other radiologic confirmation. If PET/CT scan positive in the mediastinum, lymph node status needs pathologic confirmation.  lSee Principles of Radiation Therapy (NSCL-C).  qSee Chemotherapy Regimens Used with Radiation Therapy (NSCL-E).

CLINICAL ASSESSMENT PRETREATMENT EVALUATION INITIAL TREATMENT

Stage IIIB (T1–3, N3)

• PFTs (if not previously done)  • FDG PET/CT scanj (if not previously done)  • Brain MRI with contrast  • Pathologic confirmation  of N3 disease by:  ¢ Mediastinoscopy  ¢ S u p r a c l a v i c ul a r lymph node biopsy  ¢ Thoracoscopy  ¢ N e e d l e biopsy  ¢ Mediastinotomy  ¢ E U S biopsy  ¢ E B U S biopsy

N3 negative

N3 positive

Metastatic disease

See Initial treatment for stage I–IIIA (NSCL-8)

Definitive concurrent chemoradiationl,q,u (category 1) See Treatment for Metastasis limited sites (NSCL-13) or distant disease (NSCL-15)

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uIf full-dose chemotherapy is not given concurrently with RT as initial treatment, give additional 2 cycles of full-dose chemotherapy.     Note: For more information regarding the categories and definitions used for the NCCN Evidence BlocksTM, see page EB-1. Note: All recommendations are category 2A unless otherwise indicated.  Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.  Version 4.2016, 02/29/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Evidence BlocksTM, NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®. NSCL-11

   NSCLC    RT  postopera*ve  •  Why consider PORT?  •  R1 resection (positive margins)  •  R0 resection with positive nodes

RT  postopera*ve  

• meta-analysis (Billiet 2014: 11 ECC - 2387 pts) results ~ technology

 local  relapse technology  

Cobalt 60

OS   technology  cobalt 60

Co60 a killer…

•  Several subsequent observational studies suggest some value for PORT  •  Data sources:  •  ANITA trial (post hoc analysis – IJROBP 2008)  •  SEER (JCO 2006)  •  National Cancer Database (JTO 2014)  •  PORT in N2 disease is the current topic of the Phase III European LUNG-ART randomized trial (EORTC 22055) – dose is 54 Gy in 30 fractions

PORT Based on Nodal Status

All patients N0

N1 N2

Onco  Targets  Ther.  2016;  9:  921–928.      Adjuvant  chemotherapy  plus  radiotherapy  is  superior  to  chemotherapy  following  surgical  treatment  of  stage  IIIA  N2  non-­‐small-­‐cell  lung  cancer  CT  +  RT  vs  CT  2,125  postoperaBve  chemoradiotherapy  (POCRT)  3,047  cases  of  POCT.  

OS  

DFS  …no  DFS…  

 14  trials  evalua*ng  surgery  versus  surgery  plus  radiotherapy.  Individual  data    11  trials  2343  par*cipants  (1511  deaths)    Significant  adverse  effect  of  PORT  on  survival  an  18%  rela*ve  increase  in  risk  of  death      Equivalent  to  an  absolute  detriment  of  5%  at  two  years  (2%  to  9%)  Reduc*on  on  overall  survival  from  58%  to  53%      Subgroup  analyses  showed  no  differences  in  effects  of  PORT  by  any  par*cipant  subgroup  covariate.  

survival  

local  recurrence  

dose  >  45  Gy  

-­‐  Overall  survival  was  not  significantly  different  between  surgical  and  definiBve  radiotherapy  arms      -­‐  Larer  trials  using  concurrent  radiochemotherapy  (ccRT/CT)  showed  beber  survival  at  2  years      -­‐  ccRT/CT  trials,  survival  in  the  surgical  arms  tended  to  have  an  excess  early  mortality  before  6  months  -­‐  treatment  associated  mortality  was  higher  in  the  surgical  arms    -­‐  progression-­‐free  survival,  no  significant  differences  largest  trial    advantage  for  the  surgical  arm      -­‐  Induc*on  therapy  followed  by  resec*on  or  defini*ve  radiochemotherapy  curaBve  treatment  op*ons  stage  III  NSCLC,    -­‐  Individual  treatment:  interdisciplinary  evalua*on  and  counseling.    -­‐  Based  on  heterogeneity  in  these  stages  research  on  predic*ve  factors  suppor*ng  individual  therapy  selecBon.  

Selected  topics  for  talented…  •  Bio-­‐IGRT…PET/CT  planning  •  A  flavour  of  NCCN  -­‐  RT  -­‐  NSCLL  •  NSCLC…RT  by  stages  •  SCLC…RT  LD  vs  ED  •  TRT  *ming/  AFxT  LD/  PCI  /  TRT  in  ED  •  Oligo  M1  

81  

   SCLC      Limited  extension  

Govindan JCO 2006

Incidence  &    survival  (  LD  vs  ED  )  

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)         Small Cell Lung Cancer    

Version 1.2016     NCCN.org

Version 1.2016, 06/02/15 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

Continue!

NCCN Guidelines Version 1.2016 Small Cell Lung Cancer NCCN Guidelines Index SCLC Table of Contents  Discussion TESTING RESULTS INITIAL TREATMENTj ADJUVANT TREATMENT

gSee Principles of Surgical Resection (SCL-A).  hMediastinal staging procedures include mediastinoscopy, mediastinotomy, endobronchial or esophageal ultrasound-guided biopsy, and video-assisted thoracoscopy. If endoscopic lymph node biopsy is positive, additional mediastinal staging is not required.  iPathologic mediastinal staging is not required if the patient is not a candidate for surgical resection or if non-surgical treatment is pursued.  jSee Principles of Supportive Care (SCL-B).  kSelect patients may be treated with chemotherapy/RT as an alternative to surgical resection.  lSee Principles of Chemotherapy (SCL-C). mSee Principles of Radiation Therapy (SCL-D).

Clinical stage T1-2, N0

Limited stage in excess of T1-2, N0

Pathologic mediastinal stagingg,h,i negative

Pathologic mediastinal stagingg,h positive or medically inoperable or decision made not to pursue surgical resection Good PS (0-2) Poor PS (3-4)  due to SCLC Poor PS (3-4) not due to SCLC

Lobectomyg,k (preferred) and mediastinal lymph node dissection or sampling N0

N+

Chemotherapyl Concurrent chemotherapyl+ mediastinal RTm

Good performance status (PS 0-2) Poor PS (3-4)  due to SCLC Poor PS (3-4)  not due to SCLC

Chemotherapyl + concurrent thoracic RTm (category 1) Chemotherapyl ± RTm

Individualized treatment including supportive carej

See Response Assessment + Adjuvant Treatment (SCL-5)

Chemotherapyl + concurrent RTm (category 1) Chemotherapyl ± RTm

Individualized treatment including supportive carej

See Response Assessment + Adjuvant Treatment (SCL-5)

See Response Assessment + Adjuvant Treatment (SCL-5)

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Note: All recommendations are category 2A unless otherwise indicated.  Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. SCL-3 Version 1.2016, 06/02/15 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

 TRT  LD:  doses  &  frac)ona)on  HR  =  0,8    [95%  IC:  0,6-­‐1]  

TRT    LD:  d  &  Fx  

SCLC  SCLC  

•  Fx Altered + risk of death in SCLC: similar magnitude than NCSLC but NS (p>0.05).  

•  Pts with poor PS less benefited.  •  - esofagitis severe: HR=2.41.  •  - cardio-toxicity: HR=2.96.  •  - hematologic toxicity ~ CT.

 Thoracic  RT    LD:  d  &  Fx  

TRT      LD:  )ming  QT  y  RT  

• gitis   (RR: 0,55)

early TRT esophagitis

All pts

CT not delivered

> 80 years In elderly patients with limited-stage small-cell lung cancer, modern CRT appears to confer an additional OS advantage beyond that achieved with CT alone in a large population-based cohort

8,637 patients, 3,775 (43.7%) received CT and 4,862 (56.3%) received CRT

Elderly patients (age ≥ 70 years) limited-stage small-cell lung cancer clinical stage I to III CT or CRT National Cancer Data Base 2003- 2011

J Clin Oncol. 2015 Role of Chemoradiotherapy in Elderly Patients With Limited-Stage Small-Cell Lung Cancer. Corso CD et al.

Results:  12  trials  2668  pa*ents.  9  trials  2305  pa*ents  Median  follow-­‐up  10years    ‘earlier  or  shorter’vs  ‘later  or  longer’thoracic  radiotherapy    =  overall  survival.      OS  was  significantly  in  favour  of  ‘earlier  or  shorter’  radiotherapy  compliant  with  CT      The  absolute  gain  between  ‘earlier  or  shorter’  versus  ‘later  or  longer’  thoracic  radiotherapy      in  5-­‐year  overall  survival  for  similar  CT  compliance  trials  was  7.7%      ‘earlierorshorter’  thoracicradiotherapywas  associated  with  a  higher  incidence  of  severe  acute  oesophagiBs  

PCI  LD  SCLC    EORTC  QLQ-­‐C30  significant  decline  self  reported  cogni*ve  func*on    Hopkins  verbal  learning  test  

 RTOG  0212  

Int  J  Radiat  Oncol  Biol  Phys  2013  

NCCN Guidelines Version 1.2016 Small Cell Lung Cancer NCCN Guidelines Index SCLC Table of Contents  Discussion RESPONSE ASSESSMENT FOLLOWING INITIAL THERAPY ADJUVANT TREATMENT

bBrain MRI is more sensitive than CT for identifying brain metastases and is preferred over CT.  mSee Principles of Radiation Therapy (SCL-D).  nNot recommended in patients with poor performance status or impaired neurocognitive function.

• Chest x-ray (optional)  • Chest/liver/adrenal CT with IV contrast whenever possible  • Brain MRIb (preferred) or CT with IV contrast whenever possible, if prophylactic cranial irradiation (PCI) to be given  • Other imaging studies, to assess prior sites of involvement, as clinically indicated  • CBC, platelets  • Electrolytes, LFTs, Ca, BUN, creatinine

Complete response or partial response

Stable disease

Primary progressive disease

SURVEILLANCE    After recovery from primary therapy:  • Oncology follow-up visits every 3–4 mo during y 1–2,  every 6 mo during y 3–5, then annually  4 A t every visit: H&P, chest imaging, bloodwork as clinically indicated  • New pulmonary nodule should initiate workup for potential new primary  • Smoking cessation intervention, see the NCCN Guidelines for Smoking Cessation

Limited stage

• PET/CT is not recommended for routine follow-up

For Relapse, see Subsequent Therapy (SCL-6)

See Subsequent Therapy/ Palliative Therapy (SCL-6)

Extensive stage

PCIm,n (category 1)

PCI m,n + thoracic RT m,o

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oSequential radiotherapy to thorax in selected patients with low-bulk metastatic disease and complete response (CR) or near CR after systemic therapy. Note: All recommendations are category 2A unless otherwise indicated.  Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.

SCL-5 Version 1.2016, 06/02/15 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

   SCLC      Extensive  Disease  

NCCN Guidelines Version 1.2016 Small Cell Lung Cancer NCCN Guidelines Index SCLC Table of Contents  Discussion

Extensive stage (See ST-1 for TNM Classification)

jSee Principles of Supportive Care (SCL-B).  lSee Principles of Chemotherapy (SCL-C).

STAGE INITIAL TREATMENTj    Combination chemotherapyl including supportive carej  See NCCN Guidelines for Palliative Care Extensive stage without localized symptomatic sites or brain metastases

Extensive stage + localized symptomatic sites

Extensive stage with brain metastases

• Good PS (0-2)  • Poor PS (3-4) due to SCLC • Poor PS (3-4) not due to SCLC

Individualized therapy including supportive carej  See NCCN Guidelines for Palliative Care • SVC syndrome  • Lobar obstruction  • Bone metastases

Spinal cord compression

Chemotherapyl ± RTm to symptomatic sites  If high risk of fracture due to osseous structural impairment, consider orthopedic stabilization and  palliative external-beam RTm RTm to symptomatic sites before chemotherapy unless immediate systemic therapy is required.  See NCCN Guidelines for Central Nervous System Cancers

Asymptomatic

Symptomatic

May administer chemotherapy first, with  whole-brain RTm after chemotherapyl

Whole-brain RTm before chemotherapy,l unless immediate systemic therapy is indicated

See Response Assessment + Adjuvant Treatment (SCL-5)

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mSee Principles of Radiation Therapy (SCL-D). Note: All recommendations are category 2A unless otherwise indicated.  Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.

SCL-4 Version 1.2016, 06/02/15 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

PCI  ED    

•  RCT trial EORTC   PCI ↓ % brain mts and improves DFS/OS SCLC-EDD

any!!!

10 Endpoint: 1-yr OS:    33% (TRT) vs. 28% (no TRT)    p=0.066          20 Endpoint: 2-yr OS:    13% (TRT) vs. 3% (no TRT)    p=0.004       Lancet 2014

meta-­‐analysis  of  2  randomized  trials  TRT  improves  overall  survival  and  progression-­‐free  survival  in  paBents  with  extensive  stage  SCLC,  with  a  small  incremental  risk  of  esophageal  toxicity.  

Results:  Five  retrospec*ve  studies  1691  pa*ents  315  of  them  received  PCI      In  resected  pa*ents,    PCI  improved  overall  survival  (HR:  0.52,  95%  CI:  0.33-­‐0.82)    and  reduced  brain  metastasis  risk  (RR:  0.50,  95%CI:  0.32-­‐0.78).  

Selected  topics  for  talented…  •  Bio-­‐IGRT…PET/CT  planning  •  A  flavour  of  NCCN  -­‐  RT  -­‐  NSCLL  •  NSCLC…RT  by  stages  •  SCLC…RT  LD  vs  ED  •  Oligo  M1  

103  

   NSCLC  or  SCLC      M1  oligo  rec  

NCCN Guidelines Index NSCLC TOC  Discussion NCCN Guidelines Version 4.2016 Non-Small Cell Lung Cancer NCCN Evidence BlocksTM

Disseminated metastases    jSee Principles of Surgical Therapy (NSCL-B). kSee Principles of Radiation Therapy (NSCL-C). lInterventional radiology ablation is an option for selected patients.

See Systemic Therapy for Metastatic Disease (NSCL-16)     pSee Chemotherapy Regimens Used with Radiation Therapy (NSCL-E). ccSee NCCN Guidelines for Central Nervous System Cancers. ffSee Systemic Therapy for Advanced or Metastatic Disease (NSCL-F).

Locoregional recurrence

Distant metastases

THERAPY FOR RECURRENCE AND METASTASIS Endobronchial obstruction Resectable recurrence Mediastinal lymph node recurrence Superior vena cava (SVC) obstruction

Severe hemoptysis

No prior RT Prior RT

• Laser/stent/other surgeryj  • External-beam RT or brachytherapyk  • Photodynamic therapy • Reresection (preferred)j  • External-beam RT or SABRk,l    Concurrent chemoradiationk,p Systemic therapyff • Concurrent chemoradiationk,p (if not previously given) • External-beam RTk  • SVC stent • External-beam RT or brachytherapyk  • Laser or photodynamic therapy or embolization  • Surgery

No evidence of disseminated disease Evidence of disseminated disease

Observation or  Systemic therapyff (category 2B) See Systemic Therapy for Metastatic Disease (NSCL-16)

Localized symptoms Palliative external-beam RTk Diffuse brain metastases Bone metastasis Limited metastasis

Palliative external-beam RTk,cc • Palliative external-beam RTk + orthopedic stabilization, if risk of fracture • Consider bisphosphonate therapy or denosumab See pathway for Stage IV, M1b, limited sites (NSCL-13)

See Systemic Therapy for Metastatic Disease (NSCL-16)

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Note: For more information regarding the categories and definitions used for the NCCN Evidence BlocksTM, see page EB-1. Note: All recommendations are category 2A unless otherwise indicated.  Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.  Version 4.2016, 02/29/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Evidence BlocksTM, NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®. NSCL-15

NCCN Guidelines Index NSCLC TOC  Discussion NCCN Guidelines Version 4.2016 Non-Small Cell Lung Cancer NCCN Evidence BlocksTM

hMethods for evaluation include mediastinoscopy, mediastinotomy, EBUS, EUS, and CT-guided biopsy.  jPositive PET/CT scan findings for distant disease need pathologic or other radiologic confirmation. If PET/CT scan is positive in the mediastinum, lymph node status needs pathologic confirmation.  kSee Principles of Surgical Therapy (NSCL-B).  lSee Principles of Radiation Therapy (NSCL-C).  bbAggressive local therapy may be appropriate for selected patients with limited-site oligometastatic disease.  ccSee NCCN Guidelines for Central Nervous System Cancers.  ddMay include adrenalectomy or RT (including SABR).  eePatients with N2 disease have a poor prognosis and systemic therapy should be considered.

CLINICAL ASSESSMENT PRETREATMENT EVALUATION INITIAL TREATMENT

Stage IV, M1b:  limited sitesbb

• Pathologic mediastinal lymph node evaluationh  • Bronchoscopy  • Brain MRI with contrast  • FDG PET/CT scanj (if not previously done)

Braincc

Adrenal Pathologic diagnosis by needle or resection

Surgical resection,k followed by whole brain RTl (WBRT) (category 1) or stereotactic radiosurgeryl (SRS)  or  SRS + WBRTl (category 1 for one metastasis)  or  SRSl alone    Local therapy for adrenal lesiondd (if lung lesion curable, based on T and N stage) (category 2B)ee  or  See Systemic Therapy for Metastatic Disease (NSCL-16)

T1-2,  N0-1;  T3, N0

T1-2, N2;  T3, N1-2; Any T, N3; T4, Any N

Surgical resection of lung lesionk  or  SABR of lung lesionl  or Chemotherapyff

Chemotherapyff

Surgical resection of lung lesionk or SABR of lung lesion

See Systemic Therapy for Metastatic Disease (NSCL-16)

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ffSee Systemic Therapy for Advanced or Metastatic Disease (NSCL-F).     Note: For more information regarding the categories and definitions used for the NCCN Evidence BlocksTM, see page EB-1. Note: All recommendations are category 2A unless otherwise indicated.  Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.  Version 4.2016, 02/29/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Evidence BlocksTM, NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®. NSCL-13

Oligometastatic NSCLC

AJCC  staging  subcategorizing  metasta*c  disease    -­‐  intra-­‐thoracic  (M1a)    -­‐  a  single  extra  thoracic  site  (M1b)    -­‐  diffuse  metastases  (M1c).      technological  advances  abla*ve  doses  of  radiotherapy  intra-­‐  and  extra-­‐cranial  disease  sites  (SABR)  shorter  *me  periods  and  minimal  associated  toxicity.    improvements  in  systemic  therapy,  including  pla*num-­‐based  doublet  chemotherapy,  molecular  agents  targe*ng  oncogene-­‐addicted  NSCLC,  and  immunotherapy  in  the  form  of  checkpoint  inhibitors,  have  led  to  extended  survival    radiaBon  and  immunotherapy,  poten*ally  synergis*c,  effects  in  order  to  further  improve  progression-­‐free  and  overall  survival.    

Slide courtesy Dr. D Gomez MDACC

MDACC/Colorado/LHSC Trial

First  clinical  evidences    prospecBve  +  radomized…    SBRT  consolidaBve  NSCLC!    …2016  

Key Eligibility Criteria: u  Stage IV NSCLC ≤ 3 metastatic lesions after 1st-line systemic

therapy. Regional nodes counted a 1 lesion, regardless of number of nodes

u  1st-line therapy ≥ 4 cycles of platinum doublet or ≥ 3 months of TKI for EGFR mutations or ALK re-arrangements.

Gomez  DR,  et  al.  Lancet  Oncol  2016;

Gomez  DR,  et  al.  Lancet  Oncol  2016;

Primary Endpoint = PFS

2012  –  2016  NSCLC  74  pts  estables  o  respondedores  1ra  línea  QT  <  3  mets  (75%  SBRT)    PFS  3.9  vs  11.9  meses  (p=  0.005)  

< 3 stable mets

Oligometastatic SCLC:   RTOG 0937

PCI + SBRT cosolidation

PACIFIC study, progression-free survival 17 months durvalumab group 1 year longer than the placebo group this duration is unprecedented in stage III NSCLC new distant lesions more in the placebo group than in the durvalumab group. brain metastasis developed in (11.0% vs. 5.5%).  radiotherapy anti–PD-L1–mediated pneumonitis, Treatment-related adverse 67.8% durvalumab vs 53.4% placebo. Immune-mediated adverse events was 24.2% with durvalumab and 8.1% with placebo.  

“seed and soil”

Progress  involve  NSCLC  clinical  trial  design:    -­‐  varia*ons  in  RT  dose,  frac*ona*on,  field  volume  -­‐  scheduling  with  ICIs    -­‐  systemic  an*tumour  immunity    

treatment  related  imaging  changes  TRIC  

immunoT-­‐naive  

immunoT-­‐treated  

radia*on  necrosis    pathologicaly  confirmed  

Selected  conclusions  for  talented…2017    RT  is  an  innovated  and  decisive  component  of  lung  cancer  treatment  •  Bio-­‐IGRT…PET/CT  planning:  gold  standard,  limited  nodal  RT  •  A  flavour  of  NCCN  -­‐  RT:  important  role  in  cure  +  palliaBon  •  NSCLC…RT  by  stages  •  I  SBRT:  equivalent  to  S;  tech  dependent  •  II:  PORT  R+,  N1-­‐2,  inducBon  CRT?  •  III  CRT  standard  60  Gy/  PCI  less  mets/  AFxT  no  cost-­‐eficient  •  PORT:  CT  +  RT  vs  RT  growing  evidence…  •  SCLC…RT  LD  early  TRT;  PCI  in  CR.  ED  TRT  yes  PCI  less  mets  •  Oligo  M1…  SBRT  efficient!  (survivors!)  +  systemic  therapy  

126  

 See you next time in  Madrid!    felipe.calvo@salud.madrid.org

Resected: evolution @5y

Blue dead CT yes or not Gold aive no CT Gray alive with CT Red toxic death CT