difficult cases in lung cancer
- stage III disease -
Dr. med. Wilfried EberhardtDr. med. Wilfried Eberhardt
Head, Outpatie...
difficult cases in lung cancer - stage III
- case focus -
• A 47-year old man, successfully
treated with chemoradiotherapy...
difficult cases in lung cancer - stage III
- case focus -
• combined modality for stage III
• brain metastases in lung can...
difficult cases in lung cancer - stage III
- case - 1
• 47 year old male smoker
• stage III: upper lobe / right hilar tumo...
5
Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
difficult cases in lung cancer - stage III
- case - 2
• bronchoscopy : tumor right upper lobe with
infiltration of the rig...
difficult cases in lung cancer - stage III
- case - 3
Q 1 : How would You treat this patient ?
• radiotherapy alone
• defi...
difficult cases in lung cancer - stage III
- case - 4
• induction chemotherapy
– 3 cycles cisplatin / paclitaxel
• treatme...
9
Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
difficult cases in lung cancer - stage III
- case - 5
• response : minor response ( NC / MR )
• some clinical and symptom ...
difficult cases in lung cancer - stage III
- case - 6
• definitive chemoradiation protocol
• 71 Gy ( 45 - 1.5 bid + 36 - 2...
12
Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
difficult cases in lung cancer - stage III
- case - 7
• stable clinical situation following definitive
chemoradiotherapy f...
14
Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
15
Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
difficult cases in lung cancer - stage III
- case - 8
Q 2 : How would You treat the brain metastasis ?
• surgery followed ...
difficult cases in lung cancer - stage III
- case - 9
• decision for definitive stereotactic radiotherapy
• single stereot...
18
Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
difficult cases in lung cancer - stage III
- case - 10
• after one year follow-up : development of
headaches
• brain MRI :...
20
Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
difficult cases in lung cancer - stage III
- case - 11
Q 3 : How would You treat the progression in the brain ?
• surgery ...
difficult cases in lung cancer - stage III
- case - 12
• decision was made to give oral
chemotherapy
• patient refused sur...
23
Eberhardt, Geneva 2007Eberhardt, Geneva 2007
difficult cases in lung cancer - stage III
- case - 13
• after five months oral chemotherapy, again
increase of headaches,...
25
Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
difficult cases in lung cancer - stage III
- case - 14
Q 4 : How would You treat the second brain progression ?
• surgery ...
difficult cases in lung cancer - stage III
- case - 15
• more than three and 1/2 years since
intraveneous combination chem...
28
Eberhardt, Geneva 2007Eberhardt, Geneva 2007
29
Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
difficult cases in lung cancer - stage III
- final plans for futher management -
• finally : second cycle of systemic
chem...
• some thoughts.........
Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
• ongoing tumor-free and long-term survival NED
• treatment-induced / toxic event * TOX
• local / locoregional relapse* PD...
Eberhardt Geneva 2007Eberhardt Geneva 2007
combined modality treatment of stage III NSCLCcombined modality treatment of st...
2 x cisplatin/etoposide
IIIA
(N2)
CTx : 2 x cisplatin / etoposide
RTx : 61 Gy
combined modality approaches to stage III NS...
observation
3 x docetaxel
randomization
IIIB
inop
CTx : 2 x cisplatin / etoposide
RTx : 61 Gy
combined modality approaches...
Eberhardt Geneva 2007Eberhardt Geneva 2007
combined modality treatment of stage III NSCLCcombined modality treatment of st...
Eberhardt Geneva 2007Eberhardt Geneva 2007
author pts
(n)
CTx RTx
(Gy)
LRC
( 3y )
LRC
(5y)
OS
(med)
OS
(1y; %)
ac Tox
(3/4...
CTx- CTx- CTx - C/hf-RTx (45 Gy) Restaging operable
(PET-CT) (Angio-CT)
(PET)
D E S I G N – N S C L C IIIA / III BD E S I ...
isolated brain relapse as first site of failureisolated brain relapse as first site of failure
Eberhardt, Pöttgen 2005Eber...
International Association for the Study of Lung CancerInternational Association for the Study of Lung Cancer
www.iaslc.org...
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  • "Pharmacokinetic - adjusted dosing" for angiogenesis inhibitors ...

    1. 1. difficult cases in lung cancer - stage III disease - Dr. med. Wilfried EberhardtDr. med. Wilfried Eberhardt Head, Outpatient UnitHead, Outpatient Unit Leader, Thoracic Oncology ProgrammeLeader, Thoracic Oncology Programme West German Cancer Centre EssenWest German Cancer Centre Essen Universitätsklinikum EssenUniversitätsklinikum Essen Hufelandstrasse 55, 45147 EssenHufelandstrasse 55, 45147 Essen wilfried.eberhardt@uni-essen.dewilfried.eberhardt@uni-essen.de
    2. 2. difficult cases in lung cancer - stage III - case focus - • A 47-year old man, successfully treated with chemoradiotherapy 2 years before for stage IIIB NSCLC, with symptoms of brain metastases Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
    3. 3. difficult cases in lung cancer - stage III - case focus - • combined modality for stage III • brain metastases in lung cancer • chemotherapy for brain mets Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
    4. 4. difficult cases in lung cancer - stage III - case - 1 • 47 year old male smoker • stage III: upper lobe / right hilar tumor • comorbidities – chronic obstructive lung disease ( smoking ) • symptoms – mild dyspnea – mild hemoptysis – cough Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
    5. 5. 5 Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
    6. 6. difficult cases in lung cancer - stage III - case - 2 • bronchoscopy : tumor right upper lobe with infiltration of the right tracheobronchial angle and distal end of the trachea • mediastinoscopy : lymph node metastasis right tracheobonchial, right paratracheal nodes • histopathology : adenocarcinoma G3 • abdominal CT, brain MRI, bone scan: M0 • staging: T4 N2 M0 = stage IIIB UICC / AJCC Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
    7. 7. difficult cases in lung cancer - stage III - case - 3 Q 1 : How would You treat this patient ? • radiotherapy alone • definitive concurrent chemoradiotherapy • induction chemotherapy and surgery • induction chemoradiotherapy plus surgery • palliative chemotherapy alone Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
    8. 8. difficult cases in lung cancer - stage III - case - 4 • induction chemotherapy – 3 cycles cisplatin / paclitaxel • treatment toxicity and tolerance – no major side effects – no nausea and vomiting – no infection • treatment response – decrease of mild dyspnea – no more mild hemoptysis – improvement of cough Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
    9. 9. 9 Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
    10. 10. difficult cases in lung cancer - stage III - case - 5 • response : minor response ( NC / MR ) • some clinical and symptom improvement Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
    11. 11. difficult cases in lung cancer - stage III - case - 6 • definitive chemoradiation protocol • 71 Gy ( 45 - 1.5 bid + 36 - 2 qd ) ( 6 weeks ) • one cycle concurrent chemotherapy cisplatin and vinorelbine (week 1 + 2) • further treatment response • toxicity mild – mild pneumonitis – no further side effects Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
    12. 12. 12 Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
    13. 13. difficult cases in lung cancer - stage III - case - 7 • stable clinical situation following definitive chemoradiotherapy for 2 years • no local relapse • no systemic relapse outside brain • excellent life quality, lung function • after two years follow-up : single event with seizures and headaches Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
    14. 14. 14 Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
    15. 15. 15 Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
    16. 16. difficult cases in lung cancer - stage III - case - 8 Q 2 : How would You treat the brain metastasis ? • surgery followed by whole brain radiotherapy • whole brain radiotherapy alone • stereotactic radiotherapy • chemotherapy followed by whole brain radiotherapy • chemotherapy alone then watch and wait Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
    17. 17. difficult cases in lung cancer - stage III - case - 9 • decision for definitive stereotactic radiotherapy • single stereotactic radiotherapy treatment • excellent radiographic response • no further seizures • no neurological symptoms • stable situation for one year Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
    18. 18. 18 Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
    19. 19. difficult cases in lung cancer - stage III - case - 10 • after one year follow-up : development of headaches • brain MRI : local progression of metastasis, no new metastatic sites • chest CT and abominal CT : no local or systemic relapse outside the brain Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
    20. 20. 20 Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
    21. 21. difficult cases in lung cancer - stage III - case - 11 Q 3 : How would You treat the progression in the brain ? • surgery followed by whole brain radiotherapy • re-irradiation ( whole brain or conformal boost ) • stereotactic radiotherapy again • chemotherapy followed by whole brain radiotherapy • chemotherapy alone then watch and wait Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
    22. 22. difficult cases in lung cancer - stage III - case - 12 • decision was made to give oral chemotherapy • patient refused surgical intervention as well as re-irradiation • oral treatment with temozolomide for five months • brain MRI : partial stabilization, later again progression Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
    23. 23. 23 Eberhardt, Geneva 2007Eberhardt, Geneva 2007
    24. 24. difficult cases in lung cancer - stage III - case - 13 • after five months oral chemotherapy, again increase of headaches, no seizures • patient refused surgical intervention as well as re-radiation • brain MRI : again progression of single met and increase of edema Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
    25. 25. 25 Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
    26. 26. difficult cases in lung cancer - stage III - case - 14 Q 4 : How would You treat the second brain progression ? • surgery followed by whole brain radiotherapy • re-irradiation ( whole brain or conformal boost ) • stereotactic radiotherapy again • chemotherapy followed by whole brain radiotherapy • chemotherapy alone then watch and wait Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
    27. 27. difficult cases in lung cancer - stage III - case - 15 • more than three and 1/2 years since intraveneous combination chemotherapy • decision to give intravenous chemotherapy • cisplatin and topotecan - one cycle • chemotherapy well tolerated • brain MRI : again decrease of met and reduction of edema Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
    28. 28. 28 Eberhardt, Geneva 2007Eberhardt, Geneva 2007
    29. 29. 29 Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
    30. 30. difficult cases in lung cancer - stage III - final plans for futher management - • finally : second cycle of systemic chemotherapy for brain metastases • consolidation radiotherapy planned after the second CTx cycle • either : conformal stereotactic boost again or whole brain RTx depending on results from brain MRI´s Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
    31. 31. • some thoughts......... Eberhardt et al, Geneva 2007Eberhardt et al, Geneva 2007
    32. 32. • ongoing tumor-free and long-term survival NED • treatment-induced / toxic event * TOX • local / locoregional relapse* PD • systemic relapse outside the brain* PD • brain relapse PD • second cancer / second primary SC • event due to significant comorbidities †† • ( natural death hazard ) †† Eberhardt Geneva 2007Eberhardt Geneva 2007 combined modality therapy for lung cancercombined modality therapy for lung cancer - competing risks in stage III -- competing risks in stage III - * Potentially Influenced by chemotherapy
    33. 33. Eberhardt Geneva 2007Eberhardt Geneva 2007 combined modality treatment of stage III NSCLCcombined modality treatment of stage III NSCLC - concurrent and consolidation chemotherapy -- concurrent and consolidation chemotherapy - Concurrent chemoradiotherapy Consolidation chemotherapy
    34. 34. 2 x cisplatin/etoposide IIIA (N2) CTx : 2 x cisplatin / etoposide RTx : 61 Gy combined modality approaches to stage III NSCLCcombined modality approaches to stage III NSCLC - INT 0139 trial study design -- INT 0139 trial study design - CTx / RTxCTx / RTx •Albain et al, ASCO 2004 and 2005 Eberhardt Geneva 2007Eberhardt Geneva 2007
    35. 35. observation 3 x docetaxel randomization IIIB inop CTx : 2 x cisplatin / etoposide RTx : 61 Gy combined modality approaches to stage III NSCLCcombined modality approaches to stage III NSCLC - HOG trial study design -- HOG trial study design - CTx/RTxCTx/RTx CRCR PRPR NCNC •Bedano et al, ASCO 2007, abstract 7043 Eberhardt Geneva 2007Eberhardt Geneva 2007
    36. 36. Eberhardt Geneva 2007Eberhardt Geneva 2007 combined modality treatment of stage III NSCLCcombined modality treatment of stage III NSCLC - induction chemotherapy and concurrent chemoradiotherapy -- induction chemotherapy and concurrent chemoradiotherapy - Concurrent chemoradiotherapyInduction chemotherapy
    37. 37. Eberhardt Geneva 2007Eberhardt Geneva 2007 author pts (n) CTx RTx (Gy) LRC ( 3y ) LRC (5y) OS (med) OS (1y; %) ac Tox (3/4°) Fournel 2007 64 63 2 x PT ind + 3 x PVrb cc cc 3 x PVrb + 2 x PTcons 66 66 N/R N/R 19.0 15.7 68.8 57.1 10 E 19 E multicenter randomized controlled trials in stage IIImulticenter randomized controlled trials in stage III - induction vs consolidation chemotherapy - II- induction vs consolidation chemotherapy - II E = esophagitisE = esophagitis
    38. 38. CTx- CTx- CTx - C/hf-RTx (45 Gy) Restaging operable (PET-CT) (Angio-CT) (PET) D E S I G N – N S C L C IIIA / III BD E S I G N – N S C L C IIIA / III B - randomized Phase-III study ESPATÜ -- randomized Phase-III study ESPATÜ - IIIA IIIB CTx : Cisplatin (50 mg/m2 T 1+8) / Paclitaxel (175 mg/m2 T 1) C/Hf-RTx : Cis/Nav (50/20 mg/m2 T 2+9) / 1.5 Gy bid/5 x per wk/3 wks = 45 Gy B : Boost-C/RTx : Cis/Nav (40/15 mg/m2 T 2+9(Nav)) / 20 or 26 Gy a 2 Gy ( A ) T : Thoracotomy ( B ) inoperable B B T
    39. 39. isolated brain relapse as first site of failureisolated brain relapse as first site of failure Eberhardt, Pöttgen 2005Eberhardt, Pöttgen 2005 0 12 24 36 48 60 0,00 0,05 0,10 0,15 0,20 0,25 0,30 0,35 0 12 24 36 48 60 0,00 0,05 0,10 0,15 0,20 0,25 0,30 0,35 with PCI 6 6 8 10 12 16 15 22 22 32 patients at risk 51 55 isolatedbrainrelapse asfirstsiteoffailure months without PCI 6 6 8 10 12 16 15 22 22 32 patients at risk 51 55 isolatedbrainrelapse asfirstsiteoffailure months
    40. 40. International Association for the Study of Lung CancerInternational Association for the Study of Lung Cancer www.iaslc.orgwww.iaslc.org European Society for Medical OncologyEuropean Society for Medical Oncology www.esmo.orgwww.esmo.org American Society of Clinical OncologyAmerican Society of Clinical Oncology www.asco.orgwww.asco.org

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