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Radiation Therapy of

Lung Cancer

National Cheng Kung University


Medical Center
Department of Radiation Oncology

楊明維 醫師
Basis for Prescription of
Irradiation
Patient’s general condition

Pathologic characteristics of the disease

Tumor extent (staging)

Goal of therapy (cure or palliation)

Treatment modalities

Dose of irradiation and volume


Epidemiology

Cancer death Taiwan USA


(TCOG)
Male 1st or 2nd 1st
Female 1st 1st
Total 1st 1st
No./ Y 6000 120,000
Survival of Lung Cancer
Network of lymphatic drainage of lung cancer
Lymph node metastases
from lung Ca

Hilar LNs Mediastinal Supraclavicular


LNs LNs

60%-75% 40% to 50% 2% to 15%


Clinical Presentation

S/S Incidence
Cough 75%
Hemoptysis 50%
Dyspnea 40%
Chest pain 35%
Hoarseness 5%
SVC syndrome 5%
DIAGNOSTIC WORKUP
History: metastasis symptoms

PE: H & N lymph nodes

Chest X-ray

CT: the most valuable radiologic study for evaluation,


staging, and therapeutic planning of lung cancer

MRI: mediastninum or paravetebral region

Bone scans: stage III before curative therapy


PET influenced radiation delivery in 65%
for definitive radiotherapy (Kalff et al.).

Brain CT scan: small cell carcinoma.

Pulmonary function tests: ability to


undergo surgical resection or withstand
irradiation
Sputum cytology: 20% to 30%
sensitivity

Bronchoscopic examination: 90%


positive

CT-guided Bx: 95% positive

Bx: Primary tumor lesion, scalene node


Pathology
Sputum cytology: 20% to 30% sensitivity

Bronchoscopic examination: 90% positive

CT-guided Bx: 95% positive

Bx: Primary tumor lesion, scalene node


Incidence

Taiwan (TCOG) USA

NSCLC 85-88 % 80 %
SCLA 12-15 % 20 %
Treatment Algorithm
Non-small cell lung cancer
Stage grouping (AJCC 2002)

T1 T2 T3 T4
N0 IA IB IIB IIIB
N1 IIA IIB IIIA IIIB
N2 IIIA IIIA IIIA IIIB
N3 IIIB IIIB IIIB IIIB
5-years Survival Rate for NSCLC
Treatment Algorithm
Non-small cell lung cancer
Resectable Tumors of NSCLC
Stage I, II, resectable: 5-yrs S.V 50%

Stage IIIA (T3N1-2 or N2): very heterogeneous


T3 involve chest wall: S + R/T
Limited N2 (single mediastinal LN): S + R/T

Stage IIIB: CCRT


Preoperative Irradiation

Failed to show significant improvement in


resectability or survival with use of
preoperative irradiation.
Postoperative Radiation Therapy

9 randomized trials, 2128 P’t, NSCLC


S + PORT (1056 p’t) Vs S (661)
Median follow-up 3.9 yrs

21% increase in the risk of death after 2 yrs


2 yrs overall S.V 55% -> 48% (↓7%)

Adverse effect especial in stage I & II,


little or no LN

Stage III, N2: no increased in the risk of death

(Lancet July 1998)


Postoperative Radiation Therapy

Postoperative irradiation:
1.positive or close surgical margins (T3)
2.positive hilar or mediastinal lymph
nodes
Technique of Radiation Therapy

Determined the target volume: Imaging (pre-OP), OP finding,


surgical clips

TV: ipsilateral hilum, mediastinal LNs and


ipsilateral supraclavicular area

R/T dose: 50.4 Gy in 1.8 Gy Fx or 50 Gy in 2.0 Gy Fx


50 - 70 Gy in 2-Gy fractions are usually recommended

Spinal cord < 45 Gy

Lateral field: more normal lung, more tumor target coverage

Oblique field: pneumonectomy to minimize the


dose to remaining lung
Postoperative Radiation Therapy

Postoperative irradiation: positive or


close surgical margins or positive hilar or
mediastinal lymph nodes.

Tumor doses of 60 to 70 Gy in 2-Gy


fractions are usually recommended.
Man, age: 76, cough and BWL
Man, age: 76

LUL lobectomy

Squamous cell
carcinoma

IIIA (T3N2M0)

LN(+): Hilum &


mediastinum

Margins: free
Post-OP C/T + R/T
488 P’t, LN(+), Completely removed
CCRT Vs R/T alone
C/T regimens: Cisplatin + Etoposide

CCRT R/T alone

Median S.V 38 Ms 39Ms

Adding chemotherapy to radiation therapy neither prolong survival


nor reduce locally recurrent in operable NSCLC.

( Oct. 26, 2000 NEJM )


Unresectable Tumors

Definitive radiation therapy: 40% of patients


have loco-regional advanced lung cancer
(stage lIlA or IIIB)

Medically inoperable patients with early-stage


non-small cell lung cancer

Locally recurrent: confined to chest

5-yrs S.V 5-15% ( R/T alone )


Chemoradiation Vs. R/T alone
for unresectable NSCLC
RTOG 88-08
Sequentially chemoradiation therapy
C/T regimens: CDDP 100 D1, 29
VBL D1,8,15,22,29
R/T 60Gy since D50

Sequentially R/T alone P-value

Median S.V(M) 13.2 11.4 0.04

5-yrs S.V 8% 5% 0.04


Chemoradiation Therapy
for unresectable NSCLC

Good performance status


No body weight loss or less
No contraindication to C/T or R/T
Chemotherapy alone

Poorly pulmonary function for radiotherapy

Malignant pleural effusion (T4) or


Metastasis (M1)

R/T for the aim of palliation


Man, age: 72, LLL
Man, age: 72

LLL

CT-guide Bx: carcinoma

IIIA (T3N1M0)

LN(+): Hilum

CCRT
Technique of R/T
Unresectable Tumors
Irradiation alone
Locally advanced NSCLC

RTOG(73-01) 40Gy 50Gy 60Gy

Response rate 48% 53% 56%


(CR+PR)

Local failure 44-49% 39% 33%


Technique of Radiation Therapy
Altered fractionation schemes

Split-course radiation therapy

Interval between the courses (2-4 wks) for


acute toxicity recovery
Cancer cell accelerated repopulation
during the interval
Technique of Radiation Therapy
Altered fractionation schemes

Hyperfractionated radiation scheme

RTOG trial hyperfractionated radiation scheme 69.6Gy(Bid) Vs


standard R/T 60 Gy

Failed to show survival benefit for hyperfractionation

Altered fractionation radiation therapy is not considered the


“standard of care”

(ASCO 1994;13:325)
Technique of Radiation Therapy
for locally advanced NSCLC
CHART (Continuous Hyperfractionated Accelerated Radiation Therapy)

Unresectable, stage I,II,IIIA & IIIB


TRT: 150cGy /36 Fx / 12 days ( Total 54 Gy )
Reduced 22 % relative risk of death
Squamous cell carcinoma more benefit

2-Yrs S.V

CHART(54Gy) 30%
Conventional Tx (60Gy) 20%

(Radiother Oncol 1999;52:137-148)


Technique of Radiation Therapy
Conformational three-dimensional
treatment planning

Memorial Sloan-Kettering

Conventional Vs 3-D planning for locally


advanced NSCLC

3-D CRT or IMRT could delivery of high-


dose irradiation to the target volume and
reduced the dose to lung parenchyma
IMRT 電腦治療計劃流程

照野方向設計
電腦最佳化運算

病人治療 動態式多葉準直儀設定 電腦劑量計算


Small Cell Carcinoma

5-yrs S.V Limited D’z Extensive D’z

4-8 % 7-10 % 1-2 %


Chemotherapy Vs. Chemoradiation
for L-SCLC

L-SCLC (13 randomized C/T C/T + R/T p value


Trials) (1862P’t) alone
3-yrs S.V 8.9% 14.3% 0.001

Thoracic irradiation resulted in a 14% reduction in the


mortality rate
Significant survival advantage with R/T
More benefit with R/T for younger p’t (<55y/o)
R/T decreased 30% intrathoracic tumor failure rate

(JCO 1992)
Sequence of Irradiation and
Chemotherapy
Goto et al. Concurrent Sequentially
(ASCO 1999)
Cisplatin 80 D1 + q4w x 4 q3w x 4
VP 16 100 D1-3
1.5Gy bid C/T + TRT R/T follow C/T x IV
(45Gy/3wks)
Response 97.4% 90.4%
Median S.V (M) 27.2 19.5

2-yrs S.V 55.3% 35.4%


(P = 0.057)
3yrs S.V 30.9% 20.7%
Technique of Radiation Therapy
Dose for L-stage SCLC

Induction C/T with CR: 45-50 Gy (1.8-2 Gy per fraction) to


previously involved areas and elective nodal area
Induction C/T with PR or without C/T: 54-60 Gy
CCRT: 45 Gy
Accelerated Vs Conventional R/T

Intergroup 0096 Accelerated R/T Conventional R/T P value


Regimens of C/T CCRT(CDDP 60 D1 CCRT(CDDP 60 D1
+VP-16 120 D1-3 + VP-16 120 D1-3
Q3W) X VI Q3W) X VI
Regimens of R/T 1.5Gy bid (45Gy/3wk) 1.8Gy qd (45Gy/5wk)

Median S.V(M) 29 23

2yrs S.V 47% 41% 0.04


5yrs S.V 26% 16% 0.04
Esophagitis (Gr.3) 27% 11% 0.001

(NEJM Jan 1999)


Small cell lung Ca
Limited stage
Man, age: 61

Small cell lung Ca

Limited stage

CCRT

R/T dose 4500cGy/25 Fx


Elective Cranial Irradiation

Brain Initially 2-yrs Surviving for 5


metastasis years

Incidence 20% 50% 80%

Prophylactic irradiation provides survival advantage (NEJM 1999):


3-Yr S.V: 15.3% -> 20.7% (p=0.01)
3-Yr B.M: 58.3% -> 33% (p<0.0001)
3-Yr DFS: 13.5% -> 22.3% (p<0.0001)

Timing of PCI: Post-chemotherapy 3-5 Ms

Whole brain irradiation: 30 to 35 Gy delivered in 2.0- to 2.5-Gy


Standard therapy for SCLC

Limited Disease
CCRT (EP x 4 + 45Gy) -> CR -> PCI

Extensive Disease
Role of R/T: Palliation
Palliative radiation therapy for
Lung Ca
More effectively palliated: hemoptysis or pain
More refractory: dyspnea

Protracted low dose per fraction Vs Rapid course of large


fraction size: no conclusive data proving

Medical Research Council of Great Britain: 369 P’t


1) 8.5 Gy x 2 Fx , 1wk apart
2) 3 Gy x 10 Fx 3) 4.5 Gy x 6 Fx
Relief of cough: 60%,
Palliation of hemoptysis : 80%
Median duration of palliation > = 50% of survival (median
6 months)
SUPERIOR VENA CAVA
SYNDROME
Medical emergency

Bronchogenic carcinoma: 80%


Malignant lymphoma: 10% to 18%
Benign causes (such as goiter): 2% to 3%

Radiation therapy should be initiated as soon as possible


before / after histological diagnosis

Small cell carcinoma: the mode of initial therapy is controversial;


both irradiation and chemotherapy are effective
Woman, age: 68
SVC syndrome
Woman, age: 68

SVC syndrome

Adenocarcinoma

Palliative R/T

R/T dose 5000cGy


SEQUELAE OF THERAPY
Acute Sequelae
Acute toxicities: esophagitis, cough, skin
reaction, and fatigue

Acute radiation esophagitis: begins in the


3rd week of R/T, approximately 30 Gy

Nutritional status is compromised: N-G


tube, temporary gastrostomy, or IV
hyperalimentation
SEQUELAE OF THERAPY
Acute Sequelae
Radiation pneumonitis:
Bed rest, bronchodilators, and steroids

Skin: Skin reaction is mild to moderate;


topical moisturizing creams or
ointments may relieve itching and
dryness.
SEQUELAE OF THERAPY
Late Sequelae

Pneumonitis (10% grade 2 and 4.6% grade 3)


Pulmonary fibrosis (20% grade 2 and 8% grade
3 or greater)
Esophageal stricture
Cardiac sequelae (pericardial effusion,
constrictive pericarditis, cardiomyopathy)
Spinal cord myelopathy
Brachial plexopathy.
Thanks for your
attention !
Staging System for Lung Cancer
TX

T1 Tumor ≦ 3cm in greatest dimension,


surrounded by lung or visceral pleura,
without bronchoscope evidence of invasion more
proximal than the lobar bronchus

T2 Tumor with any of the following features of size or


extent: > 3 cm in greatest dimension
Involves main bronchus, ≧ 2 cm distal to the carina
Invades the visceral pleura
Associated with atelectasis or obstructive
pneumonitis that extends to the hilar region but does
not involve the entire lung
Staging System for Lung Cancer
T3 Tumor of any size that directly invades any
of the following: chest wall (including superior
sulcus tumors), diaphragm, mediastinal
pleura, parietal pericardium; or tumor in the main
bronchus <2 cm distal to the carina but without
involvement of the carina; or associated atelectasis
or obstruct pneumonitis of the entire lung

T4 Tumor of any size that invades any of the following:


mediastinum, heart, vessels, trachea, esophagus,
vertebral body, carina; or tumor with a malignant
pleural effusion
Lymph nodes (N)

N0 No regional lymph node metastasis

N1 Metastasis in ipsilateral peribronchial or ipsilateral


hilar lymph nodes, including direct extension

N2 Metastasis in ipsilateral mediastinal or subcarinal


lymph node(s)

N3 Metastasis in contralateral mediastinal, contralateral


hilar, ipsilateral or contralateral scalene or clavicular
lymph node(s)
Preoperative Chemotherapy
No benefit for stage I and most stage II
(T1-2N1)

Neoadjuvant for stage IIB (T3N0),


IIIA(T3N1-2) with good performance status:
minimal increased in survival
Postoperative Chemotherapy or
Chemoirradiation

S + PORT + C/T (cisplatin-based) Vs S + PORT:


2% absolute reduction in risk of death
(p = .46) .

P’t with minimal BWL and highly performance


status: improved survival post-OP CCRT Vs. R/T
alone. (cisplatin-based chemotherapy)
Postoperative Chemotherapy
International Adjuvant Lung Ca Trial

1,867 P’t (NSCLC) from 148 centers in 33 countries


stage I: 36%, stage II: 25%, stage III: 39%
All surgically removable ( 65% lobectomy, 35% pneumonectomy )
C/T: cisplatin + etoposide or vinca alkaloid
R/T: + -

S + C/T S alone
5-yrs S.V 44.5% 40.4%
5-yrs DFS 39.4% 34.3%

(ASCO Jun 2003)


Sequence of Irradiation and
Chemotherapy

Most randomized trials show no benefit of thoracic


irradiation when administered after chemotherapy

CCRT > Sequential chemoradiation therapy

R/T initiation: within 6 wks or follow 2 cycles C/T

R/T is given early in the course of or concurrently with


chemotherapy.
SEQUELAE OF THERAPY
Late Sequelae
Long-term esophageal problems: stenosis, ulceration,
perforation, and fistula in 5% to 15% of patients.

Radiation-induced cardiac disease after irradiation for


lung cancer is relatively rare; pericarditis is most
common.

Spinal cord myelopathy may occur with doses higher


than 45 Gy in 1.8- to 2.0-Gy fractions; factors important
in its causation are total irradiation dose, length of the
irradiated cord, and fractionation schedule.