Radiation Oncology/NSCLC/Palliation

Multicenter randomized. 297 patients with

IIIA/B, ECOG 3-4, substantial weight loss.
RT 30/10 or 16/2. Outcome at 39 weeks

NSCLC Palliation in Advanced Disease

Median survival 57 months; 20% can survive >1
year

Both arms equally eective over initial 39

weeks
30/10 schedule more prolonged palliation,
with less worsening of symptoms

RT vs. Supportive Care

1-year OS: 30/10 20% vs. 16/2 11% (SS)

PMID 4170866 -- The survival of patients with

inoperable lung cancer: a large-scale randomized
study of radiation therapy versus placebo. (Roswit
B, Radiology. 1968 Apr;90(4):688-97.)

Conclusion: 30/10 schedule preferred due to

longer survival and longer duration of palliation

Modest prolongation (few weeks) in OS

Poland PMID 15770205 -- " prospective, randomised study to compare two palliative radiotherapy schedules for non-small-cell lung cancer
(NSCLC)" (Senkus-Konefka E, Br J Cancer. 2005
Mar 28;92(6):1038-45.)

RT
Lot of randomized trials comparing various doses
and fractionations

Randomized. 100 patients, median ECOG 2.

RT 20/5 or 16/2 (day 1, 8)

RT dose does not appear to impact median survival,

but higher dose results in higher 1-year OS

No dierence in relief
Median OS: 20/5 5.3 months vs. 16/2 8.0
months (SS)

Good ECOG status: longer schedules (30/10 up to

45/18) for better 1-year OS and longer palliation effects

Conclusion: 16/2 useful, both improved survival and better convenience

Poor ECOG status: shorter schedules (16/2, 20/5)

reasonable

Edinburgh (UK) PMID 15714933 -- Symptom

control and quality of life in people with lung cancer: a randomised trial of two palliative radiotherapy fractionation schedules. (Erridge SC, Clin Oncol (R Coll Radiol). 2005 Feb;17(1):61-7.)

Cochrane review: short schedules (1 or 2 fractions)

should be used for most patients
Australia 1984-1990 PMID 16432830 -- Unexpected long-term survival after low-dose palliative
radiotherapy for non-small cell lung cancer. (MacManus MP, Cancer. 2006 Mar 1;106(5):1110-6.)

Randomized. 149 patients. ECOG 0-3. RT

30/10 vs. 10/1
No statistical dierence in relief, but more patients with complete resolution and palliation
with 30/10

Retrospective. 2337 patients, palliative RT to

<=36 Gy
Median survival of cohort 4.6 months; 1.1%
survived progression-free >5 years.
RT dose not a factor. Caution to consider
doses to critical structures, since some patients
do survive long-term

Median OS: 5.5 months vs. 7 months (NS)

Norway PMID 14990635 -- Hypofractionated palliative radiotherapy (17 Gy per two fractions) in advanced non-small-cell lung carcinoma is comparable
to standard fractionation for symptom control and
survival: a national phase III trial. (Sundstrom S, J
Clin Oncol. 2004 Mar 1;22(5):801-10.)

Holland 1999-2002 PMID 15860852 -- Results

of the Dutch National study of the palliative eect
of irradiation using two dierent treatment schemes
for non-small-cell lung cancer. (Kramer GW, J Clin
Oncol. 2005 May 1;23(13):2962-70.)

Randomized. 421 patients with Stage III/IV,

chest symptoms or tumor threatening airway.
RT A) 17/2 vs. B) 42/15 vs. C) 50/25
1

RT

QOL and symptom relief comparable. Median OS: comparable

Median survival: 7 months vs. 9 months; 1year OS 31% vs. 36%.

Conclusion: Long course RT no improvement

over short-term RT

Conclusion: 17/2 more rapid palliative eect,

but 39/13 longer survival

NCIC CTG SC.15 (Canada) PMID 12377323 -Randomized phase III trial of single versus fractionated thoracic radiation in the palliation of patients with lung cancer (NCIC CTG SC.15). (Bezjak A, Int J Radiat Oncol Biol Phys. 2002 Nov
1;54(3):719-28.)

Groote Schuur (South Africa) 1990-1993 PMID

8581393 -- Palliative radiation for stage 3 nonsmall cell lung cancer--a prospective study of two
moderately high dose regimens. (Abratt RP, Lung
Cancer. 1995 Oct;13(2):137-43.)

Randomized. RT 10/1 vs. 20/5

Randomized. 84 patients with Stage III, WHO

0-2. RT 35/10 or 45/15

No dierence in symptom control at 1 month;

20/5 better for overall symptoms, pain, normal
activities, and QOL. Comparable toxicity

Median OS: 8.5 months in both groups. No

dierence in response rate and esophagitis
(23% vs. 41%, p=0.07)

Median survival: 2 months longer with 20/5

(SS)
Conclusion: no dierence in palliation, but
better QOL and survival with 20/5
Saarland (Germany) 1994-1998 PMID 10924977
-- A palliative accelerated irradiation regimen for
advanced non-small-cell lung cancer vs. conventionally fractionated 60 GY: results of a randomized
equivalence study. (Nestle U, Int J Radiat Oncol
Biol Phys. 2000 Aug 1;48(1):95-103.)
Randomized. 152 patients with advanced
Stage III or minimal Stage IV. Conventional
RT 60/30 vs. accelerated RT 32/16 BID
1-year OS: 37%, no dierence
Palliation adequate and comparable. Side effects comparable
Short-term course preferable to standard
60/30
Bristol (UK) PMID 9135893 -- Palliative radiotherapy for lung cancer: two versus ve fractions. (Rees GJ, Clin Oncol (R Coll Radiol).
1997;9(2):90-5.)
Randomized. 216 patients, RT 17/2 or 22.5/5
No dierence
MRC (UK) 1989-1992 PMID 8814371 -- Randomized trial of palliative two-fraction versus more
intensive 13-fraction radiotherapy for patients with
inoperable non-small cell lung cancer and good performance status. Medical Research Council Lung
Cancer Working Party. (Macbeth FR, Clin Oncol
(R Coll Radiol). 1996;8(3):167-75.)
Randomized. 509 patients. Inoperable, no
mets, good performance status. Palliative
(17/2) vs. intensive RT (39/13)

MRC (UK) PMID 1377484 -- A Medical Research Council (MRC) randomised trial of palliative
radiotherapy with two fractions or a single fraction
in patients with inoperable non-small-cell lung cancer (NSCLC) and poor performance status. Medical Research Council Lung Cancer Working Party.
(No Authors, Br J Cancer. 1992 Jun;65(6):934-41.)
Randomized. 235 patients. Main symptoms
related to thoracic tumor, poor performance
status. RT 17/2 or 10/1
Palliation: comparable, ~50% cough, ~70%
hemoptysis. Mean duration of palliation
>50% of survival time. More dysphagia in
17/2
Conclusion: 10/1 recommende for poor performance status
MRC (UK) PMID 1705140 -- Inoperable nonsmall-cell lung cancer (NSCLC): a Medical Research Council randomised trial of palliative radiotherapy with two fractions or ten fractions. Report
to the Medical Research Council by its Lung Cancer Working Party. (No Authors, Br J Cancer. 1991
Feb;63(2):265-70.)
Randomized. 369 patients. Symptoms related
to thoracic tumor. RT 17/2 (1 week apart) or
conventional (30/10 or 27/6)
Palliation: comparable, ~60% cough, ~80%
hemoptysis. Median duration of palliation
>50% of survival time
No dierence in survival. Recommend 17/2
given 1 week apart.
Hong Kong 1981-1984 PMID 2452146 -- A randomized study on palliative radiation therapy for
inoperable non small cell carcinoma of the lung.
(Teo P, Int J Radiat Oncol Biol Phys. 1988
May;14(5):867-71.)

3
Randomized. 291 patients to 45/18 vs 31.2/4
(once per week)
Median OS: 5 months, no dierence
Palliation: 45/18 superior (71% vs. 54%, SS)
RTOG 73-02 (197379) PMID 2579938, 1985
Palliative radiotherapy for inoperable carcinoma of
the lung: nal report of a RTOG multi-institutional
trial. Simpson JR et al. Int J Radiat Oncol Biol
Phys. 1985 Apr;11(4):751-8.
409 pts. T4 Any N, or Any N3 (now Stage
IIIB). Palliative therapy. Randomized to 1)
30/10 fractions, 2) 40 Gy continuous course
over 4 weeks, or 3) 40 Gy split course (as in
73-01).
No dierence in treatment arms. Palliation in
60%; 25% became symptom-free.
Review
Cochrane, 2006 PMID 17054152 -- Palliative radiotherapy regimens for non-small cell lung cancer.
(Lester JF, Cochrane Database Syst Rev. 2006 Oct
18;(4):CD002143.)
14 randomized trials reviewed.
Results: No strong evidence that any regimen
gives greater palliation
Modest survival benet (5% at 1 year, 3% at 2
years) with higher dose in patients with better
KPS
Toxicity: Some regimens associated with radiation myelitis

2003 PMID 12714878 -- Palliative thoracic radiotherapy for non-small-cell lung cancer: a systematic review. (Toy E, Am J Clin Oncol. 2003
Apr;26(2):112-20.)
Review of 12 randomized trials. RT used with
palliative intent in ~25% of patients
RT eective in controlling symptoms
No strong evidence about doses, but higher
doses lead to greater toxicity. Modest survival
benet with higher doses with good performance
Recommend short course (1-2 fxs) unless
good performance

3 Timing of RT
For patients with minimal thoracic symptoms initially, can delay treatment until symptoms develop
In one study, only 42% of delayed RT actually required RT prior to death
Norway PMID 16094739 -- Immediate or delayed radiotherapy in advanced non-small cell lung
cancer (NSCLC)? Data from a prospective randomised study. (Sundstrom S, Radiother Oncol.
2005 May;75(2):141-8.)
Data from randomised fractionation trial.
407 patients. Symptomatic (S) and nonsymptomatic patients retrospectively compared
Non-symptomatic: better baseline characteristics, better survival (11.8 months vs. 6
months)

Conclusion: Majority of patients should be

treated with short palliation (1 or 2 fractions)

Timing: baseline NS better, up to week 14 NS

developed symptoms while S had symptom relief, after week 14 no dierence

2004 PMID 15552805 -- Palliative percutaneous

radiotherapy in non-small-cell lung cancer. (Budach W, Lung Cancer. 2004 Aug;45 Suppl 2:S23945.)

Conclusion: immediate RT in patients with

no symptoms does not prevent development of
symptoms. Wait-and-see policy acceptable

Review of 11 randomized trials (10 with survival data).

Increase in total dose does not substantially
prolong median survival, but results in signicantly better 1-year survival
ECOG >=3 do not benet from higher doses,
better ECOG patients do
Poor ECOG or large distant tumor burden:
17/2 or 20/4 are appropriate
Good performance status: total dose 30-45 Gy
in 2.5-3.0 Gy/fx

MRC (UK) 1992-1999 PMID 12202326 -- Immediate versus delayed palliative thoracic radiotherapy
in patients with unresectable locally advanced nonsmall cell lung cancer and minimal thoracic symptoms: randomised controlled trial. (Falk SJ, BMJ.
2002 Aug 31;325(7362):465.)
Randomized, multicenter. 230 patient with
untreated NSCLC, minimal thoracic symptoms.
RT immediately vs. when symptomatic. 17/2
or 10/1. In delayed group, 42% received RT
prior to death. Median time to start 15 days
vs. 125 days

CHEMO VS. SUPPORTIVE CARE (MAY INCLUDE RT)

Primary outcome (alive, without symptoms at

6 months after randomization): 28% vs. 26%
(NS). No dierence in survival, activity, anxiety, depression. Adverse events more common
in immediate group

eect on drugs used, or whether single or combination. No clear dierence in benet across
subgroups
Conclusion: Chemotherapy improves OS in all
patients with advanced NSCLC

Conclusion: If minimally symptomatic, can

delay until symptoms require treatment
Paclitaxel

RT Side Eects
MRC Trials PMID 8814372 -- Radiation
myelopathy: estimates of risk in 1048 patients
in three randomized trials of palliative radiotherapy for non-small cell lung cancer.
The
Medical Research Council Lung Cancer Working
Party. (Macbeth FR, Clin Oncol (R Coll Radiol).
1996;8(3):176-81.)
Review of 3 MRC trials. 5 patients out of
1048. 3/524 patients with 17/2, 2/153 with
39/13 (could be random)
Cord doses: alpha/beta <3 Gy, possibly ~2 Gy.
Recommend not exceeding 48 Gy to spine

RT Technique
Maastricht, 2006 (Holland) PMID 16730089 -Palliative chest irradiation in sitting position in patients with bulky advanced lung cancer. (Duisters
C, Radiother Oncol. 2006 Jun;79(3):285-7. Epub
2006 May 26.)
Some patients unable to lie down because of
dyspnea. Sitting position technique developed.

Chemo vs. Supportive Care

(may include RT)

Meta-Analysis
NSCLC Collaborative Group; 2008 PMID
18678835 -- Chemotherapy in addition to supportive care improves survival in advanced non-smallcell lung cancer: a systematic review and metaanalysis of individual patient data from 16 randomized controlled trials. (NSCLC Meta-Analyses
Collaborative Group, J Clin Oncol. 2008 Oct
1;26(28):4617-25. Epub 2008 Aug 4.)
Data from 2714 patients from 16 RCTs.
Outcome: 1-year OS chemotherapy 29% vs.
supportive care 20% (HR 0.77, SS). No clear

Multicenter UK PMID 10880550 -- Randomized

trial of paclitaxel plus supportive care versus supportive care for patients with advanced non-smallcell lung cancer. (Ranson M, J Natl Cancer Inst.
2000 Jul 5;92(13):1074-80.)
Randomized. 157 with IIIB/IV with no prior
chemo, ECOG 0-2. Paclitaxel IV q3w. Supportive care included RT (but not discussed)
Median OS: paclitaxel 6.8 months vs. supportive care 4.8 months (SS); some aspects of
QOL better
Cisplatin/etoposide
Oslo (Norway) PMID 1849786 -- Symptomatic
treatment versus combination chemotherapy for patients with extensive non-small cell lung cancer.
(Kaasa S, Cancer. 1991 May 15;67(10):2443-7.)
Randomized. 87 patients with inoperable extensive NSLCL. Cisplatin/etoposide vs. supportive care (including RT 42/15)
OS: No dierence at 10.5 months, but majority of patients crossed over on disease progression.
Response rate: 21% vs. 42% (SS). Long-term
survivors only if they received both
MIC (mitomycin, ifosfamide, cisplatin)
MIC2 (198896) (Birmingham, UK)
Randomized. 351 patients with IIIB/IV to palliative care vs. palliative care + MIC
1999 PMID 10506617 Mitomycin, ifosfamide, and cisplatin in unresectable nonsmall-cell lung cancer: eects on survival and
quality of life. Cullen MH et al. J Clin Oncol.
1999 Oct;17(10):3188-94.
Median OS: 6.7 months CT + PC vs. 4.
8 months PC alone (SS)
Quality of Life: assessed in 134 patients
from start of trial to week 6, showed improvement with chemotherapy and deterioration with standard treatment.

5
2001 PMID 11843243 The benets
of chemotherapy in patient subgroups with
unresectable non-small-cell lung cancer.
Billingham LJ et al. Ann Oncol. 2001
Dec;12(12):1671-5.
Subgroup analysis: OS benet in patients
with better performance status; palliation
better but no OS benet with poor performance status

Anemia
Canada (20012003)
Randomized. Stopped early due to unplanned
safety analysis. 70 patients assigned (out of
300 planned). NSCLC unsuitable for curative therapy, baseline Hgb <12.1 g/dL. Arm
1) placebo vs. Arm 2) Epo weekly to maintain
Hgb 12-14 g/dL
2007 PMID 17312332 -- Randomized,
double-blind, placebo-controlled trial of erythropoietin in non-small-cell lung cancer with
disease-related anemia. (Wright JR, J Clin
Oncol. 2007 Mar 20;25(9):1027-32. Epub
2007 Feb 20.)
Outcome: at analysis, median OS placebo
4.2 months vs. Epo 2 months (SS)
Conclusion: Decreased overall survival
on unplanned safety analysis

SBRT in Advanced Disease

Colorado; 2009 (20052008) PMID 19373699
-- Is there a role for consolidative stereotactic
body radiation therapy following rst-line systemic
therapy for metastatic lung cancer? A patternsof-failure analysis. (Rusthoven KE, Acta Oncol.
2009;48(4):578-83.)
Retrospective. 64 patients, measurable advanced stage NSCLC, rst line systemic
chemotherapy, 34 SBRT-eligible.
Outcome: All patients progression local 64%,
distant 9%, both 27%. SBRT-eligible 68%,
14%, 18%. Time to rst progression if local
3.0 months vs if distant 5.7 months
Conclusion: Predominant failure local. Increase in time-to-progression from SBRT
could be 3 months

9 Patient Preference
National University Hospital, Singapore; 2008
PMID 19032397 -- Patients preference for radiotherapy fractionation schedule in the palliation of
symptomatic unresectable lung cancer. (Tang JI, J
Med Imaging Radiat Oncol. 2008 Oct;52(5):497502.)
Prospective. 92 patients. Choice of palliative
treatment schedule 17/2 vs 39/13. Radiation
oncologist made nal decision
Outcome: Short schedule chosen by 45% vs
long schedule 55%. Longer schedule chosen
for longer survival (90%) and better tumor
control (12%). Shorter schedule chosen for
shorter duration (80%), cost (61%), and better
symptom control (20%). Change of schedule,
56% of short course and 4% of long course
had their treatment altered by the radiation oncologist. Nevertheless, 100% patients satised
with their involvement
Conclusion: Both schedules useful, nearly half
patients felt longer survival not as important as
shorter duration and lower cost

10

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