1 difficult cases in lung cancer - stage III disease - Dr. med. Wilfried Eberhardt Dr. med. Wilfried Eberhardt Head, Outpatient Unit Head, Outpatient Unit Leader, Thoracic Oncology Programme Leader, Thoracic Oncology Programme West German Cancer Centre Essen West German Cancer Centre Essen Universitätsklinikum Essen Universitätsklinikum Essen Hufelandstrasse 55, 45147 Essen Hufelandstrasse 55, 45147 Essen [email protected][email protected]
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difficult cases in lung cancer- stage III disease -
Dr. med. Wilfried EberhardtDr. med. Wilfried Eberhardt
•A 47-year old man, successfully treated with chemoradiotherapy 2 years before for stage IIIB NSCLC, with symptoms of brain metastases
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difficult cases in lung cancer - stage III
- case focus -
• combined modality for stage III
• brain metastases in lung cancer
• chemotherapy for brain mets
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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
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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
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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
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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 2007 Eberhardt et al, Geneva 2007
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difficult cases in lung cancer - stage III
- case - 5
• response : minor response ( NC / MR )
• some clinical and symptom improvement
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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• some thoughts.........
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• 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 ) ††
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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
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combined modality treatment of stage III NSCLCcombined modality treatment of stage III NSCLC - concurrent and consolidation chemotherapy - - concurrent and consolidation chemotherapy -
combined modality approaches to stage III NSCLCcombined modality approaches to stage III NSCLC - INT 0139 trial study design - - INT 0139 trial study design -
CTx / RTx CTx / RTx
•Albain et al, ASCO 2004 and 2005
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observation
3 x docetaxel
randomization IIIB inop
CTx : 2 x cisplatin / etoposideRTx : 61 Gy
combined modality approaches to stage III NSCLCcombined modality approaches to stage III NSCLC - HOG trial study design - - HOG trial study design -
combined modality treatment of stage III NSCLCcombined modality treatment of stage III NSCLC - induction chemotherapy and concurrent chemoradiotherapy - - induction chemotherapy and concurrent chemoradiotherapy -
multicenter randomized controlled trials in stage IIImulticenter randomized controlled trials in stage III - induction vs consolidation chemotherapy - II- induction vs consolidation chemotherapy - II