2D and 3D Planning in Lung

Planning Meet

Lung Cancer
Most commonly diagnosed cancer world wide.
Also leading cause of cancer related deaths. Treatment depends upon Type, Stage of the

disease & GC of patient. 50 60% pts. Require RT at least once while 45% of pts. receive RT as initial t/t.

TMH Data (2007)

861 new cases. (5.3%) M:F = 3.7:1 Median age = 56.9/52.8 Histology :

SCC 055/861 Adenoca 336/861 SCC 206/861 NCSLC 099/861 Others 165/861

Only 37% cases are localised. 26% - distant mets. 37%

- locoregionally advanced.

ANATOMY OF LUNG
Oblique fissure: extends from

the lung surface to the hilum

Horizontal fissure: extends

from the anterior margin into oblique fissure.

Rt lung: three lobes Lt lung: two lobes, middle one

is replaced by lingula

BRONCHOPULMONARY SEGMENTS
UL
APICAL APICAL POSTERIOR ANTERIOR

ANTERIOR

LINGULA
SUP SEG
INF SEG

ML

LATERAL
MEDIAL

ANT BASAL LA T BASAL

LL
POST BASAL

ANTEROMEDIAL BASAL

MED BASAL

POSTERIOR BASAL

LATERAL BASAL

LYMPH NODE MAP:

Nomenclature*

*American College of Surgeons

Lymphatic drainage
Right upper lobe Tracheobronchial LN
Left upper lobe venous angle of same side as well

as opposite side.
Rt and lt lower lobe - subcarinal nodes and to Rt

superior mediastinum and directly into inferior mediastinum

STAGING

Tx : primary tumour can not be assessed T0 : no evidence of primary tumour. T1 : tumour </= 3 cm, no invasion more proximal than lobar bronchi T2 : >3cm, involves main bronchus >2cm distal to carina, invades visceral pleura asso with atelectasis or obstructive peumonitis not inv entire lung T3 : invades diaphragm, mediastinal pleura, parietal pericardium, bronchus <2cm from carina without inv. Carina, atelectasis or obstructive peumonitis of entire lung.

T4 : invades mediastinum, heart, great vessels, trachea, esophagus, vertebral body, carina or separate nodule in same lung or with malignant pleural effusion.

Nx : Regional lymph can not be assessed N0 : No regional lymph nodal metastasis and

N1 : Mets to ipsilateral peribronchial and/or ipsilateral hilar, intrapulmonary nodes. N2 : Mets to ipsilateral mediastinal and/or subcarinal nodes

N3 : Mets to contralateral mediastinal, contralateral hilar, contralateral scalene, or supreclavicular lymph

ipsilateral or nodes

M0 : No distal mets. M1 : Distal mets present

STAGE GROUPING

WORK UP
Clinical history, Physical Examination Performance Status, h/o wt loss Hematological : CBC, Biochem, Sr. Alk Po4, LDH Endoscopic findings

Imaging : X ray chest, CECT, PET/PET-CT

Pleural fluid cytology if PE Assessment of Cardiopulmonary function

WORK UP
PET is now standard component of staging in nan

metastatic NSCLC pts. Considered superior to CT in determining TNM stage Although CT with its better spatial resolution remains the standard assessment
Modality Sensitivity Specificity PPV NPV

CT
PET

57%
84%

82%
89%

56%
79%

83%
93%

HISTOLOGIC TYPES OF LUNG CANCER

2 major types:
Small-cell lung cancer Nonsmall-cell lung cancer, which is further subdivided into:
1. 2. 3. squamous cell carcinoma, adenocarcinoma, and large-cell carcinoma.

Origin and characteristics

Squamous cell lung cancer: commonest type in males,

central origin, manifests early

Adenocarcinoma: commonest type in females, peripheral

origin, manifests late

Large cell lung cancer: least common type, peripheral origin Small cell lung cancer: most aggressive type, central origin,

spreads quickly

RT PLANNING

POSITIONING AND IMMOBILIZATION

Pt taken on couch after explaining procedure and taking consent. Immobilization done in supine position Arms: Lateral Above head Neck: Neutral position and chin to SSN distance should be recorded Normal breathing Various immobilization boards can be used for better reproducible positions. Vac lock can be used.

Beam arrangement
AP/PA parallel opposed
Most commonly used

Lower integral dose to rest of the lung

Simple Comfortable

Easily reproducible
Spinal cord shielding Post spinal block

Radiotherapy treatment portals

Central upper lobe peripheral upper lobe

Ipsilateral supraclav to be included Inferior margin 5-6 cm below carina

No need to treat ipsilateral supraclav area If mediastinal nodes are involved then ipsilateral SCF should be treated

Phase II
Only primary tumour and

ipsilateral hilum with margin for organ uncertainties.

To reduce dose to cord
To reduce dose to other critical structures Field arrangement like ant + post oblique or both

oblique can be used

Radiation dose
Radical (definitive) RT in stage I/II NSCLC

medically unfit patients for surgery

60 64 Gy / 30 32 #/ 6 7 wks Phase I : 40 Gy / 20 # / 5 wks across mediastinum Phase II : 10 Gy / 5 # off cord with 2 cm margin to

tumour Phase III: 10 Gy / 5 # with 1 cm margin to tumour

POST OP ADJUVANT RADIOTHERAPY IN EARLY STAGE NSCLC STAGE I/II

Residual disease after lung resection

Resection with positive margins Positive lymph node status

DOSE
50-54 Gy/ 25-27 fr/ 5-6 weeks

Phase I: 40 Gy/ 20 fr across the mediastinum Phase II: 10-14 Gy/ 5-7 fr/2 cm margin (off cord).

Radical Radiation therapy in stage III/IV NSCLC

Dose and fractionation

60-64 Gy/ 30-32 fr/ 6-7 weeks Phase I : 40 Gy/ 20 fr/ 5 weeks across the mediastinum

Phase II : 10 Gy/ 6 fr/ 2 cm margin to tumour (off cord) Phase III : 10 Gy/ 6 fr/ 1 cm margin to tumour.

3D PLANNING

Conformal techniques / 3DCRT

What is the need ?
Toxicity major problem Dose escalation some possibility

Already compromised CARDIOPULMONARY function

because of Smoking, Cardiac morbidity , COPD, Atelectasis.

NORMAL TISSUE TOLERANCE TD 5/5

STRUCTURE SPINAL CORD LUNG 1/3 2/3 3/3 SELECETED END POINTS

5000
4500

5000
3000

4700
1750

MYLITIES
RADIATION PNEUMONITIS

HEART

6000

4500

4000

PERICARDITIS

ESOPHAGUS BRACHIAL PLEXUS

6000 6200

5800 6000

5500 6000

STRICTURE NERVE DAMAGE

NORMAL TISSUE TOLERANCE TD 50/5

STRUCTURE
SPINAL CORD LUNG HEART ESOPHAGUS

1/3
7000 6500 7000 7200 7700

2/3
7000 4000 5500 7000 7600 ----

3/3

2450 5000 6000 7500

BRACHIAL PLEXUS

DATA ACQUISITION
Positioning and immobilization. Reference markers placed CT scan taken in treatment position.

Contrast should be used. Extends from thyroid cartilage to umbililcus Slice thickness 5mm. Spiral mode preferred over seq. mode

STEPS

Select proper window Normal critical structures contoured first

GTV to be drawn
CTV and PTV to be generated Images and RT structures then transferred to TPS. Planning done. Plan evaluation DRR generated after plan approval. DRR matched with sim / port film. EPID taken for verification.

IMPACT OF CT WINDOW LEVEL

IMPACT OF PET ON RT PLANNING

PTV increased in 64% (detected nodes) decreased in 36% (exclusion of atelectasis)
(Erdi et al 2002)

Average reduction of PTV by 29% Average reduction of V20 by 27%

(Vanuytsel et al. 2000)

Interobserver variability reduced: mean ratio of GTV without PET: 2.31 mean ratio of GTV with PET: 1.56
(Caldwell 2001)

IMPACT OF PET ON RT PLANNING

Impact of PET: Atelectasis

IMPACT OF PET ON RT PLANNING

Impact of PET: PTV

IMPACT OF PET ON RT PLANNING

Impact of PET: PTV

IMPACT OF PET ON RT PLANNING

Limiting factors of PET -Resolution 4-8mm (depending on scanner and institution) -Registration errors (esp. with software based fusion) -Threshold value (SUV) individually to be determined Summary: PET is a promising complementary tool in RT planning of NSCLC. Its value for staging has been established and preliminary reports suggest that it may lead to more consistent definition of GTV in RT planning. However, it is still not clear, whether this will translate into better survival.

VOLUMES
GTV: Primary and Nodal disease as per Clinico

radiological findings
CTV: GTV + margins for subclinical disease
PTV: CTV + Margins for Set up error and Organ

motion ( Internal + External)

 CTV to encompass the subclinical microscopic disease

is difficult to define
Rarely mentioned in literature. Depends upon histological type and tumour volume. Proposed margin : 5 15 mm TMH: 0.7-1.0 cm margin around GTV

(Giraud 2000):

Microscopic extension mean value 5mm margin covers: margin to cover 95%

Adeno 2.69mm 80% 8mm

Squamos 1.48mm 91% 6mm

Phase1: Gross + Subclinical disease + PTV margin Phase2: Gross disease + PTV margin

RT-Planning Defining the CTV

Subclinical lymph nodes (ENI) -high risk of nodal spread in lung cancer -but value of ENI is not proven Reasons against ENI: -less than 20% locally controlled 1y after RT with conventional dose (Arriagada 1991) -need for more intense treatment to gross tumour -large volumes prevent dose escalation (normal tissue tolerance) -small primary tumor and small total tumor volume predictive (Basaki 2006, RTOG 93-11 2008) -modern chemotherapy regimens may lead to better control of microscopic disease

RT-Planning Defining the PTV

Created by adding margin to CTV
Based on institutional experience

Factors to be taken into account

Set up uncertinties Internal organ motion Respiration Cardiac motion Tumour location in lung Fixation to adjacent structures

RT-Planning Defining the PTV

Reducing respiration induced errors:

Size of movement dependent on: - tumour location in the lung - fixation to adjacent structures - lung capacity and oxygenation - patient fixation and anxiety
Average movement in normal breathing: - Upper lobe 0 - 0.5cm - Lower lobe 1.5 - 4.0cm - Middle lobe 0.5 - 2.5cm - Hilum 1.0 - 1.5cm

Steppenwoolde 2004

SOME EXAMPLES

UPPER / MIDDLE LOBE TUMOUR AND HEART DOSES

UPPER LOBE TUMOUR

MIDDLE LOBE CENTRAL TUMOUR (HEART)

MIDDLE LOBE TUMOUR (CORD)

IMRT : non uniform dose intensity maps

Uniform

Variable dose across the field to achieve a specifically designed intensity pattern Sum of all fields in 3D space delivers high doses to irregularly shaped volumes Reduces V20

Non-uniform

CONCERNS LIMITING USE OF IMRT

Increased volume of lung receiving low dose of radiation

resulting in more chances of radiation pneumonitis and decrease in DLCO.

Impact of tumour motion.
Tissue inhomogeneity requires high degree of accuracy in

dose calculaiton.
Although dosimetrically superior there is no robust

evidence to suggest that it improves the health outcome.

RESPIRATORY GATING

Technique to counteract the effect of target volume motion due to resp motion

Defines a physical window and delivers radiation when tumour passes through radiation portal
Good compliance and pul. Functions Video monitor and analyser characterizes breathing pattern and identifies full range of chest wall motion. Correlation of this data with tumour motion in simulation. Create treatment that gates the treatment beam on when the tumour falls in planed beam aperture.

4D CT BASED RESPIRATION GATED RT

Treatment beam fixed in space and gated to turn on only when

the target (or surrogate signal) comes into the pre-planned area

TOXICITIES
Oesophagitis
Radiation pnemonitis acute / late Radiation mylities Brachial plexus injury

OESOPHAGITIS

Concurrent chemotherapy and V60 were significantly associated with grade III esophagitis

LUNG TOXICITY
Related to both dose

For grade I RP
KPS Tumour location No previous surgery Concomitant chemotherapy gender

and volume effect

Acute complication

radiation pneumonitis
Late complication

fibrosis
Severely debilitating

For grade II RP High MLD V20 , V30

and fatal

MY SECONDLAST SLIDE
DONT use dose escalation and highly conformal

techniques such as IMRT for lung cancer until tumour motion can be taken into account !
In the meantime ... -Outline GTV as best as possible

-Construct CTV based on the literature

-Construct PTV based on measured tumour motion and

known setup uncertainty.

THANK YOU C U again on Monday.

Pramod Tike

MONDAY SEMINAR 11/01/09

Early Stage NSCLC: Stage I, II

Standard of care = Surgery Relapse rate

35%-50% in St. I Relapse rate 40%-60% in St. II Adjuvant radiotherapy ? Adjuvant chemotherapy ?

Adjuvant Radiotherapy
Port meta-analysis Trialist Group. Lancet 1998;352:257
9 randomised trials of postoperative RT versus surgery

(2128 patients)
21% relative increase in the risk of death with RT Reduction of OS from 55% to 48% (at 2 years) Adverse effect was greatest for Stage I,II

St.III (N2): no clear evidence of an adverse effect

Adjuvant Radiotherapy
Conclusion Postoperative RT should not be used outside of a

clinical trial in Stage I, II lung cancer, unless surgical margins are positive and repeated resection is not feasible.

Adjuvant Chemotherapy
Undetectable microscopic metastasis at diagnosis

Individual trials have not shown a significant benefit

Meta-analysis BMJ 1995;311:899:

Alkylating agents had an adverse effect

Cisplatin-based therapy:

13% reduction in risk of death (not significant)

Postoperative Chemo- and Radiotherapy

ECOG-Trial: 488 patients with stage II, IIIA

RT alone (50.4 Gy) versus

RT + 4x Cisplatin/Etoposid 39 vs 38 months (ns) 1.2 vs 1.6% 13 vs 12%

Keller et al. NEJM 2000;343:1217

Median survival TRM Local recurrence

(International Adjuvant Lung Cancer Trial Collaboratvie Group)

Cisplatin-based Adjuvant Chemotherapy

Randomised trial of 3-4 cycles of cisplatin-based

CT vs observation in patients with St. II, III LC

CT
5-Y. DFS 5-y. OS 39.4% 44.5%

no CT
34.3% 40.4%
p <0.03

p <0.03

IALT. NEJM 2004;350:351

Adjuvant Chemotherapy
Conclusion:
One should consider the use of adjuvant

platinum-based chemotherapy in patients with stage I,II or IIA NSCLC

Locally advanced NSCLC

Thoracic irradiation is the mainstay of

treatment for inoperable stage III disease

Its curative potential is extremely poor

5-year survival rates 3-5%

Locally advanced NSCLC

A meta-analysis of 22 randomised studies
10% reduction in risk of death per year Small absolute survival benefit:

showed a beneficial effect of CT added to RT

4% after 2 years 2% after 5 years

NSCLC Collaborative Group. BMJ 1995;311:899

Neoadjuvant Therapy
Pancoast`s tumor, vertebral invasion Combined neoadjuvant CT-RT should be considered
Tumors with ipsilateral mediastinal spread (N2) Poor survival with surgery alone 2 small randomised trials showed a benefit of neoadjuvant combined CT-RT Roth et al. JNCI 1994;86:673 Phase II trials report good results of neoadjuvant CT

SAKK Studies
SAKK 16/00 Preoperative CRT vs CT in NSCLC stage IIIA CT: 3 cycles docetaxel and cisplatin (D1,22,43) RT: 3 weeks of RT (44 Gy in 22 fractions)
SAKK 16/01 Preoperative CRT in NSCLC pts with operable stage IIIB disease The same regimen as 16/00

Metastasis
40-50% at diagnosis 70% during follow-up

NSCLC: chemotherapy combinations

Regimes
Cisplatin+Paclitaxel Cisplatin+Gemcitabine Cisplatin+Docetaxel Carboplatin+paclitaxel

Results (n=1155 pts.)

Response rate 19% Median survival 8 months 1-year survival

2-year survival

33% 11%

Schiller et al. NEJM 2002;346:92

Conclusion: Combined-Modality Therapy for Stage III Disease

Adding CT to radiation therapy improves survival and alters the

course of this disease

Phase III studies suggest improvement in both local control and

survival with concomitant CT-RT

Combined CT-RT should be the standard of care of patients with

good PS and minimal weight loss

The absolute gain from combined CT-RT is still modest
The role of surgery following induction CT-RT is for patients

with unresectable Cancer is being explored

Small-cell Lung Cancer

15-20% of all lung cancer Incidence:

(SCLC)

15/100000/year

Men : women = 5 : 1

SCLC
Rapid local and metastatic spread
Mediastinal lymph node metastasis in most

cases Median Survival in untreated patients 2-3 months Superior vena caval obstruction and paraneoplastic syndromes (SIADH, Cushing) Association with smoking

SCLC Staging
Limited Disease

Confined to:
One hemithorax Mediastinum Ipislateral hilar

Extensive Disease
Malignant pleura

and supraclavicular nodes

and pericard effusion Contralateral hilar and supraclavicular nodes

SCLC Therapy
No surgery; SCLC is a systemic disease
Chemotherapy is the standard of care Cisplatin+Etoposid

Limited stage SCLC: Bimodality therapy

with chemotherapy and radiotherapy

SCLC Therapy
The addition of thoracic RT significantly improves

survival in patients with LS-SCLC

Meta-analysis. Pignon et al. NEJM 1992;327:1618 14% reduction in the mortality rate 5.4% benefit in terms of OS at 3 years

Early use of RT with CT improves cure rates

SCLC Therapy
The actuarial risk of CNS metastasis developing

2 years after CR of SCLC is 35%-60%

Prophylactic cranial Irradiation is recommended

for pts. With LS-SCLC in CR

Meta-analysis:
Auperin et al. NEJM;1999:341:475

PCI: 5.4% greater absolute survival at 3 years

SCLC Results
Limited Disease:
Remission rate CR Median Survival 2-year Survival 5-year Survival

80-90% 50-60% 18-20 months 40% 15-25%

SCLC Results
Extensive Disease:
Remission rate

CR

Median Survival 2-year Survival

70-80% 20-30% 8-10 months < 10%

FLUROSCOPY
Average movement with respiration in each patient should be

recorded
Eikberg et al : 200 patients

2.4 cm in ML directions 3.9 cm in cranioquadal directions

Huang et al :

distal hilum arch lower lobe mid lobe

1 1.5 cm 0-0.5 1.5 4 cm 0.5 2.5 cm

TUMOUR EDGE DEFINITION

Visual interpretation of PET images. arbitrarily windowing, may lead significantly different apparent

tumour volumes

Automatic Image segmentation methods based on SUV either as an absolute SUV. a SUVmax of 2.5 is often used as a threshold for the distinction between

malignant and benign lesions. threshold value (a percentage of SUV max) 40% to 50% of the maximum uptake 15% for moving targets

 Important role in differentiating disease from benign

pulmonary nodule and from atelectasis.

As ENI is not routinely delivered, PET CT may help

in identification of involved nodal areas.

Despite better tumour volume deliation and reduction

of interobserver variation there is not enough robust evidence to suggest that it improves the outcome.