Patient Case Discussion

Advanced NSCLC

Robert Pirker Medical University of Vienna

ESMO International Symposium on Chest Tumors

Geneva, 30.3.-1.4.2007

Case Discussion Advanced NSCLC

A 62-year old man

with symptoms of brain metastasis

and a lung tumor

Case Discussion Advanced NSCLC

• 62-year old male

• Smoker (~40 pack years)

• No history of serious illnesses, no weight loss

• Developed severe nausea plus headache in Feb 2001; collapsed on Feb 27, 2001

• Admission to hospital

Case Discussion Advanced NSCLC

• 178 cm, 82 kg, ECOG-1

• Heart & lung normal, RR 140/80, 80/min

• Liver & spleen normal

• No enlarged lymph nodes

• No edema

• No signs of neurological deficits

Case Discussion Advanced NSCLC

• MRI of the brain: Lesion (~ 2 cm) fronto-basal on

the right site plus edema

Case Discussion Advanced NSCLC

• MRI of the brain: Lesion (~ 2 cm) fronto-basal on the right site plus edema

• Chest X-ray: Suspicion of tumor in left lung

• CT Scan of thorax & upper abdomen: Tumor left upper lobe (~ 3.5 cm)

No enlarged mediastinal lymph nodes Normal liver and adrenal glands

• Bronchoscopy: Not done

Case Discussion Advanced NSCLC

• 62-y old male smoker

• ECOG 1

• Lung cancer suspected

- Single brain lesion

- single lung lesion

- cT2N0M1

- clinical stage IV

Question

Which additional staging procedure(s) surgery wouldyou perform?

1) PET Scan

2) Bone scan

3) Both PET & bone scan

4) Other(s)

5) None

Question

Which of the following therapies would you recommend as initial therapy for this patient with NSCLC stage IV ?

1) Surgical resection of cerebral metastasis

2) Stereotactic radiosurgery of brain metastasis +/- whole-brain radiotherapy

3) Palliative chemotherapy

Case Discussion Advanced NSCLC

Dexamethasone

Resection of cerebral metastasis as initial therapy- March 20, 2001- Severe symptoms required rapid relief- Squamous cell carcinoma plus large cell carcinoma

with neuroendocrine features, compatible with NSCLC

Rapid postoperative recovery- Nausea & headache disappeared

Postoperative whole-brain radiotherapy- 30 Gy (May – June 2001)

Brain metastasis

Frequent in lung cancer - Synchronous - Metachronous

Therapy- Surgery - Stereotactic radiosurgery - Whole-brain radiotherapy - Disease status outside of the brain must be considered

Therapy of brain metastasisPeacock KH & Lesser GJ. Curr Treat Options Oncol 2006, 7, 479

Surgery- Single metastasis >3.5 cm- Immediate tumor relief necessary- Pathological diagnosis required- Small tumors with minimal edema & surgically

accessible

Stereotactic radiosurgery- Metastasis <3.5 cm in surgically inaccessible areas- Patients not suited fur surgery- Small tumors with minimal edema (even when

surgically accessible)

Stereotactic radiosurgery plus/minus whole-brain radiotherapy

Aoyama H et al. JAMA 2006, 295, 2483

• 142 patients, 1 - 4 metastases (< 3 cm)

SRS SRS+WBRT p value

Os median 8 mo 7.5 0.4

1-year 28% 38%

Brain relapse 76% 47% <0.001

Salvage therapy brain ↑

• WBRT decreases brain relapse rate but does not improve survival

Brain metastasis

Metachronous- Better prognosis than synchronous lesions (33 vs. 9 months

from time of diagnosis of NSCLC, p=0.001) but no difference from time of metastasis (12 vs. 8 months, p=0.5) Flannery TW et al. Lung Cancer 2003, 42, 327

- Surgical resection + whole brain radiotherapy Patchell RA et al. NEJM 1990, 322, 494

Synchronous - Resection of brain metastasis + whole-brain radiotherapy

Billing PS et al. J Thor Cardiovasc

Surg 2001, 122, 548 - Surgical resection of primary tumor ?

Question

Which of the following therapies would you recommend forthis patient after resection of brain metastasis

1) Resection of the primary tumor

2) Resection of the primary tumor followed by systemic chemotherapy

3) Systemic chemotherapy

4) None

Case Discussion Advanced NSCLC

• 62-y old male smoker

• Surgery of primary tumor: Lobectomy left upper lobe + mediastinal lymphadenectomy (20.4.2001) complete tumor resection

• Final diagnosis: NSCLC (squamous cell + large cell carcinoma) pT2pN0M1

pathological stage IV complete tumor resection

Question

Which treatment would you recommend for this patient afterresection of the brain metastasis (plus whole-brainradiotherapy) and after resection of the primary tumor

1) No further treatment

2) Systemic chemotherapy

Question

Which of the following protocols would you use for systemic chemotherapy in this patient with good performancestatus and normal organ functions?

1) Cisplatin-based doublet

2) Carboplatin-based doublet

3) Non-platinum-based doublet

4) Other

Case Discussion Advanced NSCLC

Cisplatin/vinorelbine, 4 cycles

- July - October 2001

Regular follow-up

- No further smoking

- CT scans thorax plus upper abdomen & MRI of the brain

Patient alive 6 years after initial diagnosis

- Last follow-up on Jan 24, 2007

Unresectable NSCLC: Follow-upASCO guidelines

Pfister DG et al. JCO 2004, 22, 3330

History & physical examination - every 3 months during first 2 years

- every 6 months thereafter through year 5

- yearly thereafter

Chest radiographs - Only in symptomatic patients

MRI brain - Only in symptomatic patients

Smoking cessation

Case Discussion Advanced NSCLC

Case 2:

• 43-year old female smoker

• NSCLC IB (1999): lobectomy right upper lobe adjuvant chemotherapy (IALT)

• 2 metachronous brain lesions (June 2000): stereotactic radiosurgery of both lesions plus whole-brain radiotherapy

• Continuous clinical remission in 2007

Case Discussion Advanced NSCLC

Case 3:

• 53-year old male smoker

• NSCLC IV (2005) with single brain metastasis: surgical resection + whole-brain radiotherapy

lobectomy systemic chemotherapy

• Brain relapse (June 2006): stereotactic radiosurgery

• Currently stable disease

Patient Case Discussion Advanced NSCLC

Summary

• Brain metastases are frequent in lung cancer (synchronous, metachronous)

• Surgery, stereotactic radiosurgery, whole-brain radiotherapy

• Resection of single brain metastasis and primary tumor can result in long-term survival in patients- with good performance status and- absence of mediastinal lymph node involvement

• Resection or radiosurgery (+/- whole-brain radiotherapy) of metachronous single metastasis can also result in long-term survival

• Not all of the treatment decisions were based on randomized trials

Question

Which therapy would you recommend for this patient withcompletely resected NSCLC stage IV ?

1) No further therapy

2) Adjuvant cranial irradiation

3) Chemotherapy

4) Chemotherapy and radiotherapy

Case studyNSCLC

• Brain metastasis frequent in patients with NSCLC

• Patients with single brain metastasis lesion and single lung lesion benefit from surgical resection of both lesions

• Postoperative cranial irradiation & systemic chemotherapy

Surgery in NSCLC IV

• Resection of single cerebral metastasis

• Resection of lung metastasis- Single lung metastasis rare at initial diagnosis

- Staging

- Secondary primary

• Resection of single bone lesion- Palliative

• Resection of adrenal gland metastasis ??

• Resection of liver metastasis- Single lesion is rare

- Far advanced disease