Tumor of any size that invades: - mediastinum, heart, great vessels, trachea, vertebral body, recurrent laryngeal nerve, esophagus; OR - tumor nodules in a different ipsilateral lobe

Adjuvant Lung CA Flashcards by Eileen Poon

What are the risk factors for Lung cancer?

Smoking
Radiation
Hazardous chemicals
Air pollution
Genetic susceptibility 
Pre-existing lung disease

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What is the median survival for Stage IA and IB Lung cancer?

IA:
95m
5y OS 65%

IB:
75m
5yOS 55%

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What is the median survival for Stage II and III Lung cancer?

IIA:
45m
5yOS 40%

IIB:
30m
5yOS 35%

IIIA:
20m
5yOS 20%

IIIB:
10m
5yOS 7%

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What is the median survival for Stage IV Lung CA

5yOS 2%

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When is invasive mediastinal staging indicated?

Central tumors
Potentially resectable T2-4
Radiological N1 involvement

Regardless whether CT/PET is positive or not.

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If CT/PET negative, but clinical T1 disease, how often will we get an incidental N2 post-op?

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Tell me about the T staging for lung cancer according to AJCC 7th edition

T1
Tumor 3cm or less, surrounded by lung/visceral pleura with no invasion more proximal than lobar bronchus

T2
Tumor >3cm but 7cm or less; OR
Tumor with any of the following:
- involves main bronchus, 2cm or less distal to the Carina
- invades visceral pleura
- a/w atelectasis or obstructive pneumonitis tt extends to the hilar region, but does no involve entire lung

T3
Tumor>7cm; OR
- directly invades chest wall/diaphragm/phrenic nerve/mediastinal pleura/parietal pericardium/main bronchus

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Tell me about the T1 staging for lung cancer

Tumor 3cm or less, surround by visceral pleura without invasion more proximal than lobar bronchus

T1a Tumor 2cm or less
T1b Tumor >2cm but 3cm or less

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Tell me about the T2 staging

T2:
Tumor >3cm, but no more than 7cm OR
- Involves main bronchus, 2cm or more distal to Carina
- invades visceral pleura
- a/w atelectasis/obstructive pneumonitis that extends to hilar region, but does not affect whole lung

T2a: Tumor >3cm, but no more than 5cm
T2b: Tumor >5cm, but no more than 7cm

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Tell me about T3

Tumor >7cm
OR
- Directly invades chest wall/diaphragm/phrenic nerve/mediastinal pleura/parietal pericardium/main bronchus

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Tell me about T4

Tumor of any size that invades:

mediastinum, heart, great vessels, trachea, vertebral body, recurrent laryngeal nerve, esophagus; OR
tumor nodules in a different ipsilateral lobe

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What Stage is T3N0M0

Stage IIB

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What Stage is T3N1/2?

What Stage is T3N3?

Stage IIIA

Stage IIIB

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What Stage is T4N0

Stage IIIA

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What stage is TxN3?

Stage IIIB

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What is a lobectomy?

Removing of one lobe
Ability to preserve pulmonary function

Thoracotomy/VATS procedure

Proximal tumors might be so readily resected by lobectomy

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What is a sleeve lobectomy?

Lobe is removed, together with part of the bronchus attached to it.

Remaining lobe(s) is then reconnected to the remaining segment of the bronchus

Indicated for proximal tumors not resectable by lobectomy

Preferred over pneumonectomy, assuming that margin-negative resection is achieved

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Tell me about Pneumonectomy

Entire lung removed

30-day mortality rate 2-11%

Significant post-op complications

Tell me about wedge resection of lung CA

Small wedge shaped resection, may be open procedure or VATS

Sometimes used for tissue

Most likely to be inferior in outcome cf lobectomy
May be alternative to lobectomy if lung function is poor/co-morbids etc.

Tell me about segmentectomy

Larger resection than wedge
Smaller resection than lobectomy

Probe should be limited to tumors 2cm or less

May benefit elderly patients >70o

Lobectomy still preferred

What is the evidence for adjuvant chemotherapy?

Data from 3 meta-analyses. (BMJ, LACE, Arriagada)

1) BMJ 1995
- 14 RCTs
- CDDP-based chemo regimens a/w absolute Benefit of 5% at 5 years
2) LACE (Lung Adjuvant Cisplatin Evaluation) Meta-analysis, Pignon JCO 2008
- JBR10, ANITA, ALPI, BLT, IALT (J.A.A.B.I)
- Deceased risk of death at 5.4% at 5 years. Vs no chemo
- survival benefit greatest for Stage II/IIIA disease
- Optimal agent to combine with CDDP not established, but most use Vinorelbine
3) Arriagada Lancet 2010
- LACE Trials + older studies
- 4% survival benefit at 5 years, regardless of RT

Tell me about the LACE meta-analysis

Pignon JCO 2008

Meta-analysis of 5 trials
- JBR.10, ALPI, ANITA, BLT, IALT
4500 patients ,med f/u 5 years

ANITA/ALPI/BLT/IALT allowed adjuvant thoracic RT at clinician’s discretion

Adjuvant chemo achieved 5.4% reduction in 5-year mortality
Stage IA: DETRIMENTAL HR 1.4
Stage IB: Not statistically significant HR 0.93

Tell me about the IALT

NEJM 2004, JCO 2010

N=2000
SCC 50%, AdenoCA 40%
Stage I 35%, stage II 25%, Stage III 40%

2 arms:

1) 3-4# CDDP+ Etoposide/Vinorelbine/Vinblastine/Vindesine +/- RT
2) Control

Med f/u 7.5 years
At 5 years, HR 0.86 5% benefit
At 7.5 years, HR 0.9, 4% benefit
After 7.5 years, HR 1.45 p sig.

Tell me about the ANITA trial

Adjuvant Navelbine International Trialist Association

Douillard et al.

Stage IB-IIIA NSCLC s/p complete resection
N=800
35% Stage IB, 25% Stage II, 40% Stage III
2 arms:
1) CDDP (100)+ Vinorelbine (30) +/- RT
2) Observation +/- RT

Med f/u 6 years

RESULTS:
Med survival 66m vs 44m (Control)
DFS 36m vs 20m 
Absolute OS benefit:
- At 1 y 28%
- At 5 years 8.6%
- At 7 years 8.4% 
5y OS (trend):
- Stage IB ~60%
- Stage II 50% v 40% (Control)
- Stage IIIA 40% vs 25% (Control)

FN Rates 10%
N/V 25%
Asthenia 25%

Tell me about JBR.10

Winton NEJM 2005 Butts et al JCO 2010 Updated N=500 Adeno 50%, Squamous 40%, Stage IB 45%, Stage IIA 15%, Stage IIB 40% (NO STAGE III) 2arms: 1) CDDP (50) D1,8 Q4w + Vinorelbine (25) weekly x16 weeks 2) Control ``` RESULTS: Med OS 95m vs 75m (Control) 5y OS 65% vs 55% Stage IB 5y OS: 11y (control) vs 10y (chemo) - Tumor >4cm may benefit - HR 1.03 Stage II 5yOS: 3.5y (Control) vs 7y ```

Tell me about the CALGB 9633 study | With RTOG/NCCTG

Gary Strauss JCO 2008 N=350 Stage IB S/p surgery 2 arms: 1) Paclitaxel (200) over 3 hours + Carboplatin AUC 6 - Q3weekly for 4# 2) Observation Med f/u 75m (6 years) RESULTS: OS: 95m vs 80m (Control) DFS: 90m vs 55m (Control) Tumor >4cm also benefitted more. 99m vs 77m - As opposed to 60m vs 78m (Control) for Tumor

How about oral Uracil-Tegafir as Adjuvant?

Japan Lung Cancer Research Group N=1000 Stage I AdenoCA lung Oral uracil-Tegafur 250mg/m2 for 2 years or no treatment RESULTS: 5y OS 88% in (uracil-Tegafur) and 85% in control group

Any role for targeted therapy in the adjuvant setting?

BR.19 Study by glenwood OS Sept 2013 ``` N=500 Stage IB 50%, Stage II 35%, Stage IIIA 13% S/p surgery and then: 1) Gefitinib 250mg OD X 2years 2) Placebo **3) Post-op Adjuvant chemo subsequently added as a protocol amendment, followed by Gefitinib maintenanceor placebo Hence: 1) Surgery --> Gefitinib 2) Surgey --> Placebo 3) Surgery --> Adj chemo --> Gefitinib 4) Surgery --> Adj Chemo --> Placebo ``` Study terminated early because ISEL and S0023 negative. Only 4% had EGFR mutations. (Out of everyone, only 70% had EGFR status determined) ``` RESULTS: DFS 4y (Gefitinib); Placebo not reached OS 5y (Gefitinib); placebo not reached ```

What is the role of neoadjuvant chemo?

1) Burdett et al. JTO 2006: Meta-analysis suggest 6% absolute improvement in OS 2) Most trials were small and underpowered or terminated early.

What is the NATCH trial about? | JCO 2010 felip et al

Resected Stage IA, IB, II or T3N1 (T2N0 take p ~65% across all arms) Mediastinoscopy mandated for LN>1cm on CT Pac (200) + Carbo AUC 6 X 3 cycles 3 groups: 1) Surgery alone 2) Preop chemo 3) Adjuvant chemo RESULTS: 5y OS ~45% 5y DFS ~35%

Is there a role for pre-op Gem/CDDP?

``` CHEST study (Chemotherapy for Early Stages Trial) Scagliotti 2012 JCO ``` N=300 Stage IA 2%, Stage IB 50%, IIA (4%), IIB 45%, IIIA 3%) 2 arms: 1) Gem (1250) D1, D8 + CDDP (75)D1 Q3w X 4 cycles --> Surgery 2) Surgery ``` RESULTS: RR to chemo 35% MEd PFS 3y vs 4y (neoadjuvant) 3y DFS: 47% vs 53% Med OS 5y vs 8 y 3y OS 60% vs 68% Benefit seen only in stage IIB/IIIA ```

What are the high risk features that will make you more inclined to discuss adjuvant chemotherapy?

``` >4cm Wedge resection Poorly differentiated tumors (including NE tumors) Vascular invasion Visceral pleural involvement Positive margins Incomplete lymph node sampling ```

What are the methods to evaluate the mediastinum?

``` Mediastinotomy Mediastinoscopy EBUS EUS CT-guided biopsy ```

When is Segmentectomy (preferred) or wedge resection appropriate in surgical therapy of lung cancer?

1) Poor pulmonary reserve 2) Other major comorbidity that contraindicates a lobectomy 3) Peripheral nodule of 2cm or less in size, with at least one of the following: - Pure AIS histology - Radiologic surveillance confirming a long doubling time of 400 days or more - nodule with 50% or more ground-glass appearance on CT scan

What is the minimum number of N2 stations sampled in account for an adequate nodal assessment?

Minimum of 3 N2 stations

What does complete resection in lung CA mean?

1) Free resection margins 2) Systematic LN Dissection or sampling 3) Highest mediastinal LN negative

What is the standard of care for inoperable Stage II (N+) and Stage III Lung CA?

Concurrent chemoRT

What constitutes a resectable stage IIIA disease

Minimal N2 disease | Treatable with lobectomy

What is recommended treatment for resectable superior sulcus tumors?

Preoperative concurrent ChemoRT

When is Post-operative RT recommended? (PORT)

1) PORT+Concurrent chemo for +resection margins | 2) PORT + post-op chemo with clinically stage I/II but upstaged to surgically to N2+ disease

When is PORT (post-operative RT) NOT recommended?

Pathologic Stage N0-1 disease | - a/w increased mortality, at least when using older RT techniques

What are centrally located tumors defined as?

Within 2cm of the proximal bronchial tree

What is the usual size limit for SABR?

5cm

SABR = SBRT | What are they?

``` SABR = Stereotactic Ablative RT SBRT = Stereotactic Body RT ```