Download Alternatives to Surgical Resection for Early Stage Lung Cancer

Alternatives to Surgical
Resection for Early Stage Lung
Cancer
Neil A. Christie MD
University of Pittsburgh Medical Center
Department of Thoracic Surgery
Allied Health Personnel Symposium
AATS 2014
Conflicts
• Educational speaker for Varian
Lung Cancer: Scope of the
Problem
• 170,000 plus cases in US each year
• Leading cause of cancer death with 15%
5 year survival
Limited Stage Lung Cancer
• 16% of new cases stage IA or IB with
tumor confined to the lung
• Surgical cure rates for early stage lung
cancer
– 75% for pathologic stage IA
– 60% for pathologic stage IB
Surgery for Lung Cancer
• anatomic lobectomy along with the N1
lymph nodes that are within the visceral
pleural envelope
• Sampling or formal lymphadenectomy of
the central mediastinal N2 lymph nodes
Medical Comorbidities and Early
Stage Lung Cancer
• Coexisting medical conditions can
preclude surgery in some patients
– COPD
– Cardiac disease
– Other medical comorbidities
– Poor functional status
Conventional XRT for Stage I
Lung Cancer
• Poor long term survival and poor local
control
Newer Ablative Therapies for
Localized Lung Cancer
• Radiofrequency Ablation (RFA)
• Stereotactic Radiotherapy (SRT)
• Potentially less morbid procedures which
also allow preservation of lung function
Talk Overview
• Radiofrequency Ablation therapy results
• Stereotactic Radiotherapy results
• Rationale for patient selection for
therapy in marginal patients with early
stage lung cancer
• Conclusions
Radiofrequency Ablation (RFA)
• Alternating current that moves from an
active electrode (within a tumor) to
dispersive electrodes (electrosurgical
return pads)
RFA System
• Generator
• Active electrode
• Dispersive electrodes (return
pads)
RF generator
Needle electrode
Patient return pads
(4 total; 2 on each thigh)
Typical Thermal
Lesions Produced
in Liver
1.0 cm
3.5 cm
Goal of RFA Therapy
• Homogeneous necrosis of the
entire tumor as well as a
surrounding 1 cm margin of
normal lung
Upper limits of RF Ablation
• Upper limit of homogenous tissue ablation
for most RF ablation systems is between 4
or 5 cm
• For ablation of tumors larger than 3 cm
multiple overlapping spheres or cylinders
of ablation are required with active
electrode probe repositioning
Published Results of RFA
Therapy
• 22 peer reviewed manuscripts
reporting an experience in over 900
patients since 1st report in year 2000
RFA Procedure
• Anesthetic
– 50% done with conscious sedation
– 40% done with general anesthesia
– 10% done with epidural or local anesthesia
only
• Mean hospital stay 1.3 to 6 days with
range from same day discharge to 35 days
Results- Tumor Response After RFA
Pre-RFA
1 month post-RFA
3 months post-RFA
Tumor Ablation Rates
• Tumor diameter is an important
prognostic variable
• Complete necrosis much more likely
in tumors < 3 cm
Tumor Ablation Rates
• Herrera University of Pittsburgh with
modified RECIST criteria
– Complete or partial response
• 67% of tumors < 5cm
• 33% of tumors > 5 cm
• Akebashi with contrast enhanced CT and
PET
– Complete ablation
• 69% of tumors < 3 cm
• 39% of tumors >3 cm
Ablate and Resect Studies
• Nguyen and Ambrogi
–Complete necrosis in 38% and 67%
respectively
–Complete ablation more probable in
tumors < 2 cm
Survival following RFA
• Ambrogi
– Median survival for stage I lung cancer 18.9
months
• Tumor < 3 cm median survival 30.5 mo
• Tumor > 3 cm median survival 14.9 mo
Survival following RFA
• Simon with 75 stage I lung cancer patients
median survival 29 months
– 1 year 78%
– 2 year 57%
– 3 year 36%
– 4 year 27%
– 5 year 27%
Complications of RFA
• Mortality
–One large study of 153 patients had
a 2.6% mortality rate
Complications of RFA
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Pneumothorax: 0 – 54% (usually 20%)
Pneumonia: 0 – 22% (1 fatal)
COPD Exacerbation: 0 – 6%
ARDS: 0 – 3% (3 fatal)
Pulmonary abscess: 0 – 6%
Hemoptysis: 0 – 12% (1 fatal)
Hemothorax: 0 – 4%
Pleural effusion: 0 – 4%
Empyema: 1%
BP fistula: 1%
Pulmonary Contusion: 0 – 1%
Stereotactic Radiotherapy (SRT)
Conventional Radiotherapy
• Standard approach 45 – 66 Gy total
dose in 1.8 to 2 Gy fractions
• 5 year survival rates 10 – 30%
Dose Escalation
• Benefit to dose escalation with dose –
response relationship with local control
and survival
• Dose escalation limited by toxicity to lung
with radiation pneumonitis
3-D Conformal RT
• More sophisticated planning techniques
that limit treatment volumes and
radiation to normal lung tissue to allow
safer dose escalation
• Still have significant local failure
Stereotactic Radiotherapy (SRT)
• Three dimensional conformal planning
techniques
• Stereotactic targeting with image
guidance
• Systems to decrease the effect of lung
motion
Tumor targeting
• Ablative doses to the tumor
• Limit radiation to normal tissue to
prevent toxicity
Compensating for Respiratory
Motion
• Tumor tracking
• Gating
• Respiratory inhibition
Diagnostic
X-Ray Source
Linear
Accelerator
Robotic Arm
Image
Detectors
Treatment
Couch
Dosimetry
• Potent dose which confidently hits the
target while having a very sharp fall off
dose gradient outside the region of the
tumor
• Multiple bream paths from multiple
directions
Pre Rx
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Radiosurgery Results
• Onishi 2007
• Hypofractionated stereotactic radiotherapy
for stage I lung cancer in 257 patients in a
Japanese multi-institutional study
• 18 – 75 Gray in 1 – 22 fractions
• Median F/U 38 months
• 5.4% incidence of symptomatic radiation
pneumonitis
Radiosurgery Results
• Local recurrence in 36 patients (14%)
– BED> 100 Gray 8.4%
– BED< 100 Gray42.9%
• 5 year survival 71% for those with BED>
100 vs 30% for BED< 100
• Nodal recurrences in 11%
– 5.1% isolated to LN
– 3.1% LN and local
– 2.8% LN and distal
Radiosurgery Results
• Timmerman 2003
• Dose escalation study in 37 patients with
medically inoperable stage I lung cancer
• 3 fractions starting at 8 Gray and escalated to 20
Gray
• No change in pulmonary function
• 2 patients with grade three pneumonitis
• 87% tumor response rate
• 6 patients experienced relapse by 15 months
Radiosurgery results
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Timmerman 2006
70 patients withT1 or T2 lung cancer
60 to 66 Gray in three fractions over 1 – 2 weeks
Local control at 2 years was 95%
Median overall survival 32 months
Grade 3 – 5 severe toxicity or death in 14
patients
• Median time to toxicity was 10.5 months
Radiosurgery Results
• Central tumor predictor of
toxicity
• Large tumor predictor of toxicity
Outcomes with current Regimen
• 20 Gy X 3 peripheral tumors
• 12 Gy X 4 central tumors
• Minimal toxicity / no change in PFTs
• Local control rates 85 to 90 %
Phase II Trial SBRT peripheral
tumors
• Timmerman et al. JAMA 2010
• Phase II North American Multicenter trial
SBRT for T1T2N0 NSCLC (<5cm)
peripheral medically inoperable
• 18 Gy x 3, 3 year F/U
• 55 patients (44T1, 11T2)
Timmerman et al.
• 51% complete response rate at 6.5
months post Rx
• Complete or partial response in 89%
patients
Timmerman et al
• 1/55 patients had recurrence at treated
site
• 3 year primary control rate 98%
• 3/55 patients had recurrence within the
involved lobe
• 3 year primary tumor and involved lobe
control rate 91%
Timmerman et al.
• 2/55 regional nodal failures (33 and 36
months)
• 3 year local/regional control rate 87%
• 11/55 metastatic disease
Timmerman et al.
• 26 patients died in F/U (10 of cancer)
• 3 year disease free survival 48%
• 3 year overall survival 56%
• No treatment related deaths
• 2 patients with grade III or IV adverse
events
SBRT vs Wedge Resection
• Grills et al. Journal of Clinical Oncology, 2010.
• T1-T2NO NSCLC (< 5 cm)
• Wedge resection 69 patients
• SBRT 58 patients (medically inoperable)
– 12 Gy x 4 or 12 Gy x 5
• Staged PET/CT +/- mediastinoscopy (30%
wedge patients and 20% SBRT patients)
Grills et al.
• Mean FEV1 1.39 both groups
• SBRT patients older and higher
comorbidity index
• Median F/U 2.5 years
Grills et al.
Loc
Rec
Reg
Rec
Loc
Reg
Rec
Dist
Mets
Over
Surv
Can
Surv
SBRT 4%
n=55
4%
9%
19%
72%
93%
Wedg 20%
n=69
18%
27%
21%
87%
94%
SBRT vs Surgery
• Crabtree et al. JTCVS 2010
• 462 surgical patients F/U 31 months
– 49 wedge, 16 seg, 375 lobe, 22 pneum
• 76 SBRT patients F/U 19 months
• Staged with CT and PET/CT
• Surgical patients younger, lower comorbidity
scores, better pulmonary function
Crabtree et al.
Overall
Survival
surgery
68%
Cancer
Specific
Survival
82%
SBRT
32%
82%
3 year follow-up
Local
Control
96%
89%
Crabtree et al.
• Propensity matching to find 2 similar
groups wrt age, clinical stage and
comorbidity
• No difference in overall survival, cancer
specific survival, or local control
• In high risk group operative mortality 7%
with 44% complication rate (27%
pneumonia or resp failure)
Conclusions
• RFA results comparable to conventional
XRT, inferior to surgery and SBRT
• Await results of ACOSOG phase II trial
with standardized technique
Conclusions
• SBRT has excellent local control and
better than expected regional control
• Long term recurrences may be underestimated due to high non-cancer deaths
in patient population studied
• Results of SBRT in operative candidates
now showing 80% T1N0 and 70% T2N0
Selection of Therapy in Patients
with Pulmonary Compromise
Treatment Options for Stage I NSCLC
(T1/T2 N0 M0)
• Surgical Resection
– Lobectomy
– Sublobar Resection
• Segmentectomy
• Wedge Resection
• Nonsurgical Therapy
– Ablative techniques
• Stereotactic Radiosurgery
• Radiofrequency Ablation
– Radiation Therapy
• No Treatment
Lobectomy versus Sublobar Resection
/ Ablation
Type of
Resection:
Lobectomy
Sublobar
Resection/
Ablation
Local
Control
+
+
-
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+
Survival
Lung
Function
-
Local Control: Lobectomy vs
Sublobar Resection
• Ginsberg RJ, Rubinstein LV. Randomized Trial
of Lobectomy versus limited Resection for
T1N0 NSCLC. Annals of Thoracic Surgery
1995. 60(3):615.
• Local recurrence
– 21/122 (17%) sublobar resection
– 8/125 (6%) lobectomy
Survival: Lobectomy vs sublobar
resection
• LCSG
• Limited resection associated with 30%
increase in overall death rate and 50%
increase in death with cancer
5 year survival after resection
Okada et al
Tumor size lobectomy
Segmental
resection
Wedge
resection
20 mm or
less
96.7%
92.4%
85.7%
21 to 30
mm
87.4%
84.6%
39.4%
Greater
than 30
mm
81.3%
62.9%
0%
Lung Fuction: Lobectomy vs
sublobar resection
• LCSG
• FEV1 at 6 and 12 months F/U was
preserved in the sublobar resection group
versus the lobectomy group
Periop mortality in patients with
very poor lung Function (NETT)
• 140 patients
FEV1 < 20%
DLCO < 20%
• Perioperative mortality 28.6%
Comorbidity, Functional Status and
Survival in Stage I NSCLC
• All were independent predictors of survival
for lung cancer; independent of age and
treatment modality
• Age was not a predictor of poor outcome
• When KPS < 70 and CIRS-G4 no benefit
to Surgery
– Surgical survival 11%
– XRT survival 6%
Lung Resection in the elderly
• Port et al. Surgical resection for lung cancer in the
octogenarian. Chest 2004 126:733.
• 61 patients mean age 82 (range 80 – 87)
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4 pneumonectomies
46 lobectomies
6 segmentectomies
5 wedge resections
Death 1/61 (1.6%)
Major complications 13%
Length of stay 7 days
82% 5 year survival for Stage IA NSCLC
Minimally Invasive Lung resection
(Thoracoscopic Lobectomy)
• Onaitis et al. Thoracoscopic lobectomy is a safe and
versatile procedure. Experience with 500
consecutive patients. Annals of Surgery 2006;
24(3):420
• 1.6% conversion rate
• Periop mortality 1%
• Periop morbidity
– A fib 10%
– Resp failure 1.2 %
– MI 0.4%
• Median length of hospitalization 3 days
• NSCLC Stage IA 2 year survival 85%
Sx vs SBRT
• Surgery
– Pros
• Definitive pathologic diagnosis
• Enables invasive nodal staging
• Adjuvant therapy in node pos patients
– Cons
• Morbidity and mortality
• Possible benign disease
Sx vs SBRT
• SBRT
– Pros
• 5 year local control rates better than 90%
• Outpatient and mild toxicity
• Prservation of lung function and quality of life
– Cons
• Treatment without pathologic verification
• Post treatment fibrosis masking local disease
recurrence
• Clinical staging underestimates regional
nodal involvement in up to 25% of cases
and would not be addressed by SRT
– Cure rate for stage II lung cancer with
surgery alone is 40% and would expected to
be 0% with SRT
• Determination of residual disease by
imaging is not reliable so salvage
surgery could be delayed allowing
progression of cancer to an advanced
(incurable) stage
Thank You
Lung Ablation Techniques, University of Pittsburgh