Lung Cancer Overview

Scott Babington

Radiation Oncologist

Christchurch Oncology Service

Outline

Introduction

Smoking cessation

Staging

PET

NSCLC management

SCLC management

Malignant Mesothelioma

Introduction

Fifth most common cancer

Leading cause of cancer death

23% male cancer deaths

15% female cancer deaths

Incidence

falling in males

increasing in females

Age

Peak incidence in 50-60s age groups

Smoking Cessation

Smoking is the greatest public health catastrophe The most preventable causes

of premature death

4600 deaths in NZ each year due to active smoking

400 more deaths due to passive smoking

Smokers who die of a tobacco related cause lose on average 13 years of life compared to non-smokers

If left unchecked – 10 million people will die prematurely in 2030

Hospital Cessation Programmes

Smoke free environment implemented

Health professionals critical to making a

significant difference in smoking cessation

ABC for smoking cessation

Ask

Brief advice

Cessation support

Smoking cessation kits available everywhere

Quitline/ Smokechange/ Aukati Kaipapa

https://smokingcessationabc.org.nz/

Pathology

Four main histological subtypes Lung Cancer:

Squamous cell carcinoma (20-40%) more common in men

strongest association with smoking

Adenocarcinoma (20-40%) increasingly common, now most common subtype in

males and females

Large/undifferentiated carcinoma (5-10%)

Small cell carcinoma (20-25%)

Malignant Mesothelioma

Staging Lung Cancer -

NSCLC and SCLC

NSCLC = Non-Small Cell Lung Cancer

SCLC = Small Cell Lung Cancer

Seventh edition TNM Staging Manual

Staging: T1 less than 3cm

T1a ≤ 2cm

T1b 2 – 3cm

T2: > 3cm and ≤7cmInvolves main bronchus > 2cm carina

Invades visceral pleura

Atelectasis that extends to hilum

T3: Tumour >7cm

OR

Invades:

- chest wall,

- diaphragm, phrenic nerve

- mediastinal pleura

- parietal pericardium

- main bronchus <2cm from carina

Atelectasis entire lung

Separate tumour nodules in same

lobe

T4: Invades mediastinum or

separate tumour nodules in different

ipsilateral lobe

Nodal Levels

N1: Ipsilateral Hilar Lymph Nodes

N2: Ipsilateral Mediastinum

or Subcarinal Lymph Nodes

N3: Contralateral Hilum,

Mediastinum, or Supraclavicular

Node(s)

M1a: Separate tumour nodule(s) in

contralateral lobe, pleural nodules

Malignant pleural or pericardial

effusion

M1b: Distant Metastases

Stage Grouping

IA T1a-T1b N0

IB T2a N0

IIA T1a-T2a N1

T2b N0

IIB T2b N1

T3 N0

Generally surgically treated

Stage Grouping

Stage IIIA mixed group

T3 N1

T1a-3 N2

T4 N0-1

IIIB Any T N3

T4 N2

Stage IV M1a or M1b

Survival - NSCLC

Goldstraw P et al J Thorac Oncol. 2007;2: 706–714

PET CT Imaging

PET Positron Emission Tomography Radiopharmceuticals or "tracers,"

Labeled isotopes of carbon, oxygen, nitrogen and fluorine

FDG = radiolabelled Glucose

Isotopes mimic sugars, water, proteins and oxygen

Assesses cellular-level metabolic status of a disease

Useful for initial and follow up assessments

CT Computerised Tomography

PET CT = both PET scanner and CT combined

Patient in same position for both, so

better localisation of PET scan images

PET CT Staging

NZ Government

Indications:

Preoperative

Pre Radical

Radiation Therapy

Stage Migration

Not SCLC

PETCT Process

Fasted from midnight

PET radioisotope (FDG)

injected

Patient lies still 45 mins

Scan takes one hour

CT scan at completion

Non-Small Cell Lung

Cancer (NSCLC)

NSCLC - Natural History

Primary tumour grows

Lymphovascular invasion

Segmental, Lobular then mediastinal lymph

nodes

Haematological spread

Brain

Bone

Liver/ adrenals

Lung

Management NSCLC

Early stages (I, II)

Surgery

Radiation Therapy (RT) alone

if contraindication to surgery

Stereotactic Body Radiation Therapy (SBRT)

Stage IIIA/B

Surgery if possible, ?Adjuvant RT1,2

Neoadjuvant chemotherapy – controversial

Concomitant CT and RT

1 PORT metanalysis. Lancet 1998;352:257-63

2 Lung cancer study group. NEJM 1986;315:1377-81

Chemotherapy in NSCLC

Neoadjuvant

Chemotherapy alone increased local recurrence

RCT similar survival to RT alone1

Concomitant ChemoRT Locally advanced NSCLC

Palliative Chemotherapy Cisplatin containing – increased OS

Vinorelbine

Biological therapies very expensive and limited availability

1 Kubota K, et al. JCO 1994;12:1547-52

NSCLC Collaborative group Metanalysis

52 Randomised controlled trials (RCTs)

Cisplatinum containing regimens best

Surgery plus Chemotherapy

Hazard Ratio (HR) 0.87

Absolute benefit @ 5 years 5%

Radical RT plus Chemotherapy HR 0.87

Absolute benefit @ 2 years 4%

Best supportive care plus Chemotherapy HR 0.73

Absolute survival benefit @ 1 year 10%

NSCLC collaborative group. BMJ 1995;311:899-909

Evidence for Chemotherapy in

NSCLC

Neoadjuvant Chemotherapy then

Surgery for NSCLC

Standard of care in the USA1

2 widely quoted RCTs, Roth2 and Roselle3

widely criticised, 60 patients in each trial

groups imbalanced, poor outcome in surgical group

Depierre4 355 patients (Surgery +/- neoadj CT)

Non-significant trend toward increased OS (p=0.15)

1 ASCO Clinical Practice Guidelines JCO 1997;15:2996-3018

2 Roth JA et al. JNCI 1994;86:673-80

3 Roselle R, et al. NEJM 1994;330:153-8

4 Depierre A et al. JCO 2002;20:247-53

Radical Radiation Therapy alone

‘QRI’ 50Gy in 20 fractions

T1 or T2 tumours

27% 5 yr OS overall1

Locally advanced NSCLC

60Gy in 30 fractions

lowest intrathoracic recurrence

55% complete response ==> 40% 2 yr OS

average 25% 2 yr OS

1 Gauden et al. Chest 1995;108:1278-82

2 Perez et al. Cancer 1980;45:2744-53

Altered Fractionation

Accelerated1

60Gy in 30# bd

Very toxic, no better than Concomitant ChemoRT

CHART2

54Gy in 36#, 3 fractions per day

12 consecutive days

2 yr OS 29%, CF (60Gy) 20%, p=0.008

Investigating CHART WELL +/- CT

1 Ball et al. Rad Onc 1999;52:129-36

2 Saunders et al. Rad Onc 1999;52:137-148

Concurrent CT+RT evidence

RTOG 9410: 610 patients, three arms

locally adv unresectable stage II-III NSCLC

2 concurrent ChemoRT vs Chemo and HF

cisplatinum/vinblastine, conc vs sequent (60Gy)

cisplatinum and oral etoposide and 69.6Gy bd

CV seq CV conc CE HF

Med OS 14.6% 17.0% 15.2%

4 yr OS 12% 21% 17%

p=0.046 p=0.296

Curran WJ et al. Prog Proc ASCO 2003;22:621 abstr

Toxicity ChemoRT

Chemotherapy related

Cisplatin

Nausea/vomiting

Hydration paramount

Etoposide

Nausea

1% allergy

Alopecia

Neutropenic risk

‘Green card’

Lethargy

Radiation related

Tiredness

Oesophagitis

Paracetamol 250/5ml

qds 1/2hr ac

Patient toxicity folders

RT video/DVD

The Future?

CHISEL

Trans-Tasman Radiation

Oncology Group

Highly Conformal

Hypofractionated

(“stereotactic”) Radiation

Therapy (SBRT)

54Gy in three fractions

T1 and T2a node

negative NSCLC

Palliative Radiation Therapy

Palliative regimens (MRC)1-3

10 Gray single fraction

16 Gray in two fractions one week apart

36 Gray in 12 daily fractions

20 Gray in five fractions

Very commonly used

6 Gray Upper ‘Hemibody’

Bone metastasesMRC lung cancer working party

1 Clinical Oncology 1996;8:167-175

2 Br J Cancer 1991;63:265-70

3 Br J Cancer 1992;65:934-41

36 Gray in 12 Daily Fractions

Criteria: Stage IIIA/B NSCLC

too advanced for surgery or radical RT

WHO Performance status 0-2

No significant weight loss

No evidence of metastases

16Gy in 2# 36Gy in 12#

Median survival 7 months 9 months p=0.03

One year OS 31% 36%

Two year OS 9% 12%

17 Gray in 2 Fractions,

One Week ApartCriteria Inoperable NSCLC

Symptomatic

expected survival over one month

no performance status criteria

metastases permitted

17Gy/2# 30Gy/10#

Median OS 6mths 6months

One year OS 20% 23%

Two year OS 5% 5%

Palln: Cough/Haem 65/81% 56/86%

10 Gray Single Fraction

Criteria Inoperable NSCLC

Poor performance status

main symptoms related to intrathoracic ca

Palliation 17Gy/2# 10Gy single#

Cough 48% 56%

Haemoptysis 75% 72%

Chest pain 59% 72%

Anorexia 49% 55%

Median OS 100 days 122 days

Small Cell Lung

Cancer (SCLC)

SCLC - Natural History

Sub-mucosal cancer

usually arises centrally

Rapid doubling time = very aggressive

Metastasises widely and early

Extrathoracic lymph nodes positive 25%

Systemic metastases present in 70%

“depends on how hard you look”

Liver

Bone

CNS

Limited Stage SCLC

Aim of treatment - Radical

Concurrent chemotherapy and RT

Four three weekly cycles of:

Cisplatinum 60mg/m2, day 1

Etoposide 120mg/m2, days 1,2,3

RT: 45Gy in 30#, bd, reference point

GTV, bilateral mediastinal and hilar nodes

plus 1-1.5cm margin

Start RT with first cycle CT

Murray et al. JCO 1993;11:336-344

Daily Versus bd Fractionation

Turrisi AT et al. NEJM 1999;340:265-71

417 patients

all concurrent CT - Cisplatin/Etoposide

randomised to 45Gy in 25# (CF) or

45Gy in 30#, bd (AHF)

CF AHF

Local recurrence 52% 36% p=0.06

2 year OS 41% 47%

5 year OS 26% 16% p=0.04

CF = Conventional Fractionation, AHF = Accelerated Hyperfractionation

Initial vs Delayed HF

Jeremic B, et al. JCO 1997;15:893-900

107 patients

Concurrent Carboplatin/Etoposide

randomised to weeks 1-4, or

weeks 6-9

all received AHF RT 54Gy in 36# bd

Chemotherapy start Early Delayed

Median OS 34mths 26mths

5yr OS 30% 15%

Christchurch Oncology Service

Protocol for SCLC

Limited SCLC

Good performance status

Able to tolerate bd RT and Chemotherapy

Turissi protocol – then PCI

Limited but not able to tolerate above

Chemotherapy first then chest RT and PCI

Extensive = Metastatic disease

Palliative Chemotherapy

Consider consolidative chest RT

Consider PCI

Prophylactic Cranial RT

Following 12 weeks of treatment

CT scan Chest

If patient in Complete Response (CR)

25Gy in 10# WBI

(We use 30Gy in 15 fractions)

Rationale for Prophylactic

Cranial RT

Prophylactic Cranial Irradiation Overview

Collaborative Group

Metanalysis 987 individual patient data

Prophylactic CRT vs no CRT

Relative risk death 0.87 (0.73-0.97, p=0.01)

Absolute survival benefit 5.4% @ three years

15.3% to 20.7%

Increased disease-free survival RR 0.75 (0.65-0.86,

p<0.001)

Decreased brain metastases RR 0.46 (0.38-0.57, p<0.001)

Palliation SCLC

RT 20Gy in 5 fractions

Chemotherapy

Very responsive

Carboplatin and/or

Etoposide

PCI used in extensive

disease in CR with

chemotherapy

Malignant Mesothelioma

Malignant Mesothelioma

Natural History

Pleural effusion/plaques

Often difficult to diagnose

Seldom spreads

systemically

Incurable

Surgery

Extra-pulmonary

pneumonectomy (EPP)

Pleurodesis

Radiation Therapy

Whole thorax irradiation

post EPP

Port-site irradiation

21Gy in three daily

fractions

Chemotherapy

Cisplatin and

Pemetrexed

Christchurch Oncology Service

Summary

Prevention better than cure Smoking cessation – get

involved

https://smokingcessationabc.org.nz/

Quitline 0800 778 778

Smokechange ph 351 1009

Aukati Kaipapa ph 347 0490

Staging Small and Non-Small Cell Lung Cancer same system

Surgery for early stage NSCLC

Chemotherapy Combination with RT - cure

Palliative NSCLC - Cisplatin improves survival

Malignant Mesothelioma

New ‘biologicals’

Radiation Therapy ChemoRT for locally

advanced NSCLC and SCLC

Consoldative Thoracic RT

Prophylactic Cranial Irradiation

Palliative irradiation

Port site RT in Malig Meso