Modern and Evolving Modalities of Lung Cancer Treatment

1
Modern and Evolving Modalities of Lung Cancer
Treatment

• Mr Vladimir Anikin
• Consultant Thoracic Surgeon
• Harefield Hospital, London UK

2
Is Lung Cancer Still a Problem?

• Mortality in US peaked in 1993
• Remains the most common malignant tumour
• Most common cause of cancer-related death in the
  world
• Year 2011 in US 221,130 new cases, 156,940
  deaths
• No evidence of decreasing incidence in the world
• NCI investment in lung cancer in 2010 - 281.9M
• 
  

3
Worldwide Incidence of Lung Cancer
Continent Incidence (rate) Incidence (rate)
Continent Males Females
Asia 472,791 (30.1) 188,559 (11.0)
Europe 296,364 (56.8) 78,396 (11.3)
North America 131,481 (61.2) 94,160 (35.6)
Central/South America 38,587 (21.8) 15,646 (7.3)
Africa 14,752 (7.0) 4,776 (2.0)
New Zealand and Australia 6,539 (39.1) 3,285 (17.4)
Total gt 1.1 million gt 1.1 million

1. Jemal et al. CA Cancer J Clin 200858(2)

4
Old Problem New Challenges

• Increasing number of patients with peripheral
  nodules (screening, availability of CT)
• Adenocarcinoma in non-smokers
• Age and co-morbidity of patients
• Peak in effectiveness of classic treatment
  modalities

5
Early Diagnosis of Lung Cancer
20 reduction of lung cancer mortality with low
dose helical CT scan
Aberle at al., EngJMed,2011
6
New Methods in Diagnostics of Lung Cancer

• Improvement of existent
• Aggressive approach to the
• establishing of pathology
• Bronchoscopy with electromagnetic
• navigation
• Detecting of circulating tumour cells

7
Advances in modern staging of lung cancer

• Videomediastinoscopy
• EBUS
• PET scan
• Detection of circulating
• tumour cells (evolving)

8
Endobronchial Ultrasound

• Minimally invasive
• No GA
• Very safe
• Very expensive
• Main technique of mediastinal and hilar lymph
  node biopsy
• Potentials to be a treatment modality

9
Circulating Tumour Cells

• CTCs identified over a century ago
• Historical difficulties in reliable CTC isolation
  has lead to limited research
• Extraction and analysis cells from blood sample
  (usually anything up to 10 mls) - Allows for a
  real time non-invasive liquid biopsy
• Recent technological developments have led to
  renewed interest
• Strong evidence from recent studies suggesting
  CTC detection and levels in the blood can predict
  prognosis and overall survival
• Multitude of isolation devices available with
  different functionalities

10
Technologies of Detecting Circulating Tumour
Cells (to name a few)
Expression of biomarker Physical properties
Veridex CellSearch (FDA approved breast, prostate and pancreatic) EpCAM based detection ScreenCell Size capture - filtration
Cynvenio LiquidBiopsy Immunomagnetic platform RareCell ISET Size capture - filtration
Cytotrack Fluorescent scanning Clearbridge CTC0 CED0 Physical properties microfluidic technology
Fluxion IsoFlux system Antibody labelled
Siliconbiosystems DEPArray Fluorescent scanning
MagSweeper Immunomagnetic platform
11
ScreenCell Device

• Blood sample processed with buffer to fix cells
• Processed sample introduced in to device and
  filtered via mean of vacuum suction
• CTCs remain on membrane filter (cannot pass
  through pores due to size)
• Staining and cellular characterisation can be
  done directly on filter

12
ScreenCell and Lung Cancer (Harefield Results)

• 23 patients with primary lung cancer
• Blood samples were taken prior to surgery,
  processed in the ScreenCell device, stained
  directly (HE)
• 73 (18 of 23) of samples contained cells
  suspicious of cancer
• Generally more suspicious cells or even clusters
  of cells were seen in patients with advanced lung
  cancer

13
CTC of Lung Cancer

• X 40 magnification
• Features typical of abnormal suspicious cancer
  cells

14
Treatment of Lung Cancer

• Radical
• Early stages of peripheral tumours
• Early tumours of major airways
• Locally advanced tumours
• Palliative
• Compromised airways
• Pleural effusion
• Symptomatic local tumour invasion

15
Old Disease - New Philosophy of Treatment

• Targeted chemotherapy
• If tumour cannot be eradicated it may be possible
  to stop it progressing
• Attempted radical approach in oligometastatic
  disease

16
Available and Evolving Modalities of Radical
Treatment of Lung Cancer

• Lung resections
• - classic
• - video-assisted
• - robotic
• Radical radiotherapy
• Ablative technologies (RFA, microwave,
  cryoablation, irreversible electroporation,
  cyberknife, photodynamic therapy)
• Molecularly targeted therapy
• Lung cancer vaccine

17
Limitations in Lung Cancer Surgery

• Still the main curative modality
• Resection and repair
• Functional difficult to overcome
• Anatomical a small room for improvement
• Medico-legal because of growing public
  expectations

18
New Options in Classic Surgery of Lung Cancer

• Extracorporeal resections
• Resections with extracorporeal oxygenation
• Tissue engineering using stem cells
• Expensive
• Limited to a very small group of patients

19
Extracorporeal Lung Resections

• Explantation of the lung with tumour
• Resection of the tumour and repair
• Reimplantation
• With or without perfusion during procedure

20
VATS Anatomical Lung Resections

• Widely accepted technique with excellent results
• Lobectomy or segmentectomy
• Tendency to decrease the volume of resection
• Expensive
• Further significant improvement is unlikely
• Applicable on in patients with early stages

21
Limitations of Advanced VATS Lung Resections

• Just a new version of old surgery
• Danger of doing it at any cost
• Increased potentials for major mistakes
• Diluted experience in traditional technique

22
Robotic Lung Resections

• Popular and attractive
• No obvious advantages in results
• Very expensive
• Time consuming
• Wide potentials for
• further development

23
Ablative Techniques

• Widely used to treat functionally inoperable
  patients
• No surgical staging
• Time consuming and expensive
• Limited experience with operable patients
• Operator dependent

24
How do ablative techniques work?

• Local tumour destruction with heat, cold,
  chemicals, changing cellular wall permeation,
  irradiation
• Absorption of destroyed tissue
• Formation of scar

25
Ablative Technologies
26
What is the difference?

• Timing
• The shape of ablation zone
• Effective depth of ablation
• Potentials for bleeding
• Uniformity of ablation
• Simplicity of equipment
• All differences
  are subtle

27
Comparison of Healing

• Heat Injury
• Destroys all layers of tissue
• Destruction of arterioles and venules
• Cell migration delayed
• Greater necrosis
• Irregular margins

• Cold Injury
• Connective tissue survives
• Arterioles preserved
• Cell migration occurs soon
• Lesser necrosis
• Smooth margins

28
Stereotactic Radiotherapy (Cyberknife)

• Dose 45-60 Gy in three fractions
• Pathology is available in 50 of patients
• Requires CT-guided placement of markers
• Excellent local control (90-95) at 1-2 years
• May be used in patients with either peripheral or
  central tumours

29
Radiofrequency Ablation
30
RFA Results for primary NSCLC The Harefield
experience

• 38 functionally inoperable patients
• Complications in 20 (53) patients
• Local progression 7(15.8)
• Mean time for progression 11.4 months
• Overall survival for 1 year 86.8
• Cancer specific survival at 1 year 92.1

31
Survival after RFA of primary lung cancer

• Median survival - 33.4.months
• Cancer-specific survival 41.4 months
• Actuarial survival
• 1 year 89
• 3 years 59
• 5 years 40
• 
  Ambrogi et al., 2011

32
RFA for Lung Cancer Recurrence

• 44 patients
• Recurrence after surgical resection
• Recurrence-free 3 year survival 41.1
• 5 year survival 55.7
• 
  
  Kadama et al., 2011

33
Expanding use of RFA or cryoablation in lung
cancer treatment

• Treating recurrent tumours with 55.7 5-year
  survival (Kadama et al., 2011)
• Salvage treatment of advanced lung cancer after
  radiochemotherapy (Li et al, 2011)

34
Intraoperative VATS cryoablation forming the
iceball
35
Survival of patients after intraoperative
cryoablation The Harefield experience

• Number of patients - 24
• Still alive 15
• Died from tumour 5
• Died from other causes 3
• Lost for follow up 1
• Median survival 21 (1-41) months

36
Salvage treatment of advanced lung cancer

• Argon helium cryoablation
• Stage III tumours after radiochemotherapy
• No significant complications
• Ten out of twelve survived one year
• 
  Li et al, 2011

37
Microwave Ablation of Lung Cancer

• Dielectric hysteresis leading to the direct
  heating of tissue
• Heating of a large volume of tissue
• Relatively large size of the probe
• No thrombosis in the adjacent zone
• Results are comparable with the results of RFA

38
Irreversible electroporation

• Electric discharge
• Formation of permanent pores in the cell membrane
• No change in temperature
• Minimally invasive
• Sharp demarcation of the zone of necrosis

39
Clinical experience with irreversible
electroporation (Nanoknife)

• Still in its infancy
• Interest is growing rapidly
• Expensive technology
• May be safe to use in the vicinity of major
  vessels and for large tumours
• Sharp demarcation line of the ablated area

40
Evaluation of treatment response after
non-operative therapy for lung cancer

• Strict imaging survey
• Familiarity with
• imaging characteristics
• Recognition of unexpected
• findings
• Options to treat incomplete
• response or recurrence
• Post-treatment PET scan
• is the most promising tool
• 
  
  Eradat et al., 2011 Vahdat et a., 2010
• 
  
  
  
  
  
  

41
Potentials of Ablative Technologies

• Improvement of equipment
• Combining of VATS/open approach with CT for
  locally advanced tumours
• Developing indications for each particular
  modality
• Synergy with nanoparticle-based chemotherapy
• Endobronchial access to the tumour
  (electromagnetic navigation, CT-guided
  bronchoscopy)

42
Non-surgical modalities in lung cancer treatment

• Individualised chemotherapy with gene testing
• Clinical use of lung cancer vaccine

43
Purposes of palliative treatment in patients with
lung cancer surgical perspectives

• To maintain adequate bronchial lumen
• Control of problematic cough
• Control of haemoptysis
• Control of pleural effusion
• Prevention and treatment of malignant fistulas

44
Endobronchial Interventions

• Endobronchial stenting
• Endobronchial tumour ablation
• (mechanical, cryotherapy,
• laser, argon beam, ethanol injection)
• Combination of techniques

45
Conclusions

• Early diagnosis and better staging are essential
  for improving results of treatment
• Anatomical surgical resections remain the gold
  standard with tendency to reduce resection volume
• Ablative technologies are likely to become a part
  of radical treatment of lung cancer
• Individualised chemotherapy and lung cancer
  vaccine may be used as adjuncts to local
  eradication of tumour
• Palliative endobronchial interventions improve
  quality of life and survival in patients with
  advanced lung cancer