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Steroids, Radiotherapy, Chemotherapy and Stents for Superior Vena Caval

Obstruction in Carcinoma of the Bronchus: a Systematic Review

Article  in  Clinical Oncology · November 2002

DOI: 10.1053/clon.2002.0095 · Source: PubMed

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Clinical Oncology (2002) 14: 338–351
doi:10.1053/clon.2002.0095, available online at http://www.idealibrary.com on

Systematic Review
Steroids, Radiotherapy, Chemotherapy and Stents for
Superior Vena Caval Obstruction in Carcinoma of the
Bronchus: a Systematic Review
N. P. Rowell*, F. V. Gleeson†
*Kent Oncology Centre, Maidstone Hospital, Hermitage Lane, Maidstone, Kent ME16 9QQ; †Department of
Radiology, Oxford Radcliffe Hospital (Churchill Site), Old Road, Headington, Oxford OX3 7LJ, U.K.

ABSTRACT:
Objective: To conduct a systematic review to determine the relative effectiveness of treatments currently employed in the
management of superior vena caval obstruction (SVCO).
Search strategy: Electronic searching of the Cochrane Clinical Trials Register, Medline and Embase with identification of further
studies from references cited in trials identified by electronic searching.
Selection criteria: Both randomized and non-randomized controlled trials in which patients with carcinoma of the bronchus and
SVCO had been treated with any combination of steroids, chemotherapy, radiotherapy or insertion of an expandable metal stent.
Data collection and analysis: There were three randomized and 98 non-randomized studies of which two and 44 respectively met the
inclusion criteria.
Main results: Superior vena caval obstruction was present at diagnosis in 10.0% of patients with small cell lung cancer (SCLC) and
1.7% of patients with non-small cell lung cancer (NSCLC). In one small randomized trial in SCLC, the rate of SVCO relapse was
not significantly reduced by giving radiotherapy on completion of chemotherapy. In another, in NSCLC, the addition of induction
chemotherapy to a course of synchronous chemo-radiotherapy did not provide greater relief of SVCO.
In SCLC chemotherapy and/or radiotherapy relieved SVCO in 77%; 17% of those treated had a recurrence of SVCO. In NSCLC,
60% had relief of SVCO following chemotherapy and/or radiotherapy; 19% of those treated had a recurrence of SVCO. Insertion
of an SVC stent relieved SVCO in 95%; 11% of those treated had further SVCO but recanalization was possible in the majority
resulting in a long-term patency rate of 92%. Morbidity following stent insertion was greater if thrombolytics were administered.
Reviewers’ conclusions: Chemotherapy and radiotherapy are effective in relieving SVCO in a proportion of patients whilst stent
insertion may provide relief in a higher proportion and more rapidly. The effectiveness of steroids and the optimal timing of stent
insertion (whether at diagnosis or following failure of other modalities) remain uncertain. Rowell, N. P., Gleeson, F. V. (2002).
Clinical Oncology 14, 338–351  2002 The Royal College of Radiologists. Published by Elsevier Science Ltd. All rights reserved.

Key words: Non-small cell lung cancer, small cell lung cancer, superior vena cava obstruction, stent, radiotherapy, chemotherapy

Received: 18 February 2002 Accepted: 27 February 2002

Introduction The diagnosis of SVCO is usually made clinically in

Background
Superior vena caval obstruction (SVCO) is an uncom-
mon manifestation of carcinoma of the bronchus (both
small cell and non-small cell) affecting a minority of
patients at some point in their illness. Malignant causes
now account for in excess of 90% of cases of SVCO [1].
In the majority, this is due to carcinoma of the bronchus
but less commonly lymphoma, metastatic disease
and intrathoracic tumours such as mesothelioma and
thymoma may be responsible.
Author for correspondence: Dr N. P. Rowell, Consultant in Clinical
Oncology, Kent Oncology Centre, Maidstone Hospital, Hermitage
Lane, Maidstone, Kent ME16 9QQ. Tel: 01622 225103 (direct line);
Fax: 01622 225074; E-mail: nrowell@mkoc.demon.co.uk
the first instance, the presence of neck swelling and
distended veins over the chest being the most constant
features [2]. There may also be swelling of one or both
arms. Shortness of breath, hoarse voice and headache
may also be caused by SVCO although these symptoms
may arise from other manifestations of lung cancer.
Superior vena caval obstruction results from the com-
pression of the superior vena cava (SVC) by either a
tumour arising in the right main or upper lobe bronchus
or by large volume mediastinal lymphadenopathy most
commonly arising from the right paratracheal or pre-
carinal lymph node stations. Four patterns of venous
collateral return have been described [3]. Symptoms tend
to be more severe when the SVC is obstructed below the
entry of the azygos vein.

0936–6555/02/040338+14 $35.00/0  2002 The Royal College of Radiologists. Published by Elsevier Science Ltd. All rights reserved.
      
Computerized tomography (CT) or magnetic reso-
nance imaging (MRI) is of value in defining the extent of
tumour to assist radiotherapy planning or to act as a
baseline for assessment of response to chemotherapy.
Contrast enhanced spiral or multi-slice CT is now able
to identify accurately the site of occlusion or stenosis
and the presence of associated intravascular thrombus.
At times impending SVCO may be apparent from CT
or MRI prior to the development of symptoms [4].
Venography, mostly carried out as a prelude to stenting,
will also determine whether there is SVC stenosis or
occlusion and the extent of any thrombus formation.
In the past, SVCO has been considered a medical
emergency. For the majority of patients, this is now
believed not to be the case as outcome is unrelated to
duration of symptoms [5,6]. The danger of SVCO (and
risk of death) is said to be increased by airway obstruc-
tion from laryngeal or bronchial oedema or coma from
cerebral oedema though it is unclear to what extent these
processes contribute in the majority of patients. There is
no commonly accepted scoring system to assess the
severity of SVCO or help identify patients at greatest
risk.
Treatment is either purely symptomatic or directed at
the underlying cause. Traditionally, treatment has in-
cluded systemic steroids (prednisolone or dexametha-
sone) and either radiotherapy (mostly for non-small cell
cancers) or chemotherapy (mostly for small cell cancers).
Steroids are generally used in conjunction with radio-
therapy because of concern about radiation-induced
oedema. Historically, this gave rise to two patterns of
radiotherapy fractionation; one started with small frac-
tions (c1 Gy) and increased the fraction size as treat-
ment progressed [7], the other started with larger
fractions of 4 Gy for the first few days to encourage
more rapid relief of SVCO and then continued with
smaller fractions of 1.8–2 Gy daily until the desired total
dose was reached [8]. Diuretics have been used in the
past with anecdotal reports of benefit. Despite treatment
with radiotherapy or chemotherapy, a proportion of
patients fail to respond and symptoms persist. This can
be due either to persisting tumour mass or to SVC
thrombosis. In others, SVCO, may relapse after a period
of time. More recently the percutaneous placement of
expandable metal stents within the superior vena cava
has allowed rapid restoration of the normal pattern of
flow in the majority of patients with rapid resolution of
symptoms. This procedure is however time-consuming,
particularly if thrombolysis is required, and stents are
costly. In some cases, more than one stent needs to be
deployed. It is currently unclear whether it would be
preferable to perform stenting earlier in the course of the
disease.
Objectives
The purpose of this review is to define more clearly the
relative merits of the different treatment modalities and
339
help identify ways in which quality of life may be most
reliably improved and maintained in patients with this
unpleasant complication of lung cancer.
Where possible data from randomized controlled
trials were to be reviewed. In their absence, data from
non-randomized studies would be reviewed to obtain a
measure of the likely treatment effect for each type of
intervention. This should assist those involved in the
design of future randomized trials in SVCO. Caution
must be exercised in the interpretation of data from
non-randomized studies because of the well-recognized
potential for bias.
Materials and Methods
Criteria for considering studies in this review
Criteria for inclusion of studies in this review were
established at the outset. These were as follows:
Types of studies
Evidence from randomized controlled trials was sought
in the first instance. In the event of there being an
insufficient number of these, results would be reported
from non-randomized studies, bearing in mind that such
evidence is prone to several sorts of bias.
Types of participants
Patients of any age with histologically-proven carcinoma
of the bronchus (small cell or non-small cell) and a
clinical diagnosis of SVCO.
Types of intervention
Steroid (prednisolone or dexamethasone) therapy,
chemotherapy (administered orally or intravenously),
external beam megavoltage radiotherapy, insertion of an
expandable metal stent into the superior vena cava (with
or without thrombolysis or anticoagulation) or any
combination of these treatments.
Types of outcome measures
Evidence of the following was sought: relief of symp-
toms (swelling of the face, neck and arms, venous
distension, headache and shortness of breath), effects on
quality of life, treatment morbidity, subsequent relapse
of SVCO (incidence, time to relapse and whether or not
re-treatment was undertaken) and median survival.
Search strategy
Randomized trials were identified by searching the
Cochrane Clinical Trials Register (Cochrane Library
2001, Issue 2) and both randomized and non-
randomized trials from 1966 to 2001 by searching
340  
Medline and Excerpta Medica (Embase). The search
strategies are shown in Appendix I. Electronic searches
were updated in July 2001. Further studies were ident-
ified from references cited in those papers identified by
electronic searching.
Methods of the review
Each paper was read in its entirety. Where possible,
non-English language papers were translated before
being reviewed; for some, only an English abstract was
available. Data was extracted from each paper and
summarized by the first reviewer. For included studies,
the data was checked for accuracy by the second re-
viewer and for excluded studies the reasons for exclusion
were confirmed by the second reviewer. Any discrepancy
or disagreement was resolved by discussion.
Description of the studies
Three randomized trials were identified – one was a
subset of a larger randomized trial [9] in which patients
with small cell lung cancer were randomized to chemo-
therapy vs chemotherapy plus radiotherapy. The second
randomized patients with non-small cell lung cancer to
chemotherapy followed by radiotherapy with synchro-
nous cisplatin or to immediate treatment with radio-
therapy with synchronous cisplatin [10], [Martins SJ,
personal communication]. The third study randomized
patients with small cell and non-small cell lung cancer to
radiotherapy plus nitrogen mustard vs radiotherapy
alone [8]; this study was excluded as not all patients had
a diagnosis of lung cancer.
There were 98 non-randomized studies of which
almost all were retrospective. Fifty-six reported the use
of chemotherapy and/or radiotherapy and 44 the use of
stents (two reported both). There were no studies report-
ing the effectiveness of steroid therapy. Thirty-four
radiotherapy/chemotherapy studies and 21 stent studies
(54 references) did not meet the inclusion criteria and
were excluded. In one study [11], only that part of the
study relating to treatment of patients with small cell
lung cancer met the inclusion criteria. Reasons for
exclusion are set out in Table 1. Twenty-two
radiotherapy/chemotherapy studies and 23 stent studies
(44 references) form the basis of this review. Because of
the heterogeneity of studies, only narrative synthesis was
undertaken.
Methodological Quality of Included Studies
Randomized studies
The randomization procedure was explicitly stated in the
non-small cell study [10] but not the small cell study [9].
Both appeared to have been analysed on an intention to
treat basis and no patients were excluded from analysis.
Patient characteristics
Frequently, studies included patients with conditions
other than lung cancer and pre-treatment details related
to the whole group and not solely those with lung
cancer. Though not a criterion for inclusion, data on
performance status (a major determinant of outcome in
lung cancer) was reported only in the minority of
studies. In seven of the stenting studies, the histological
subtype of lung cancer was not stated.
End-points
In general, criteria for relief of SVCO were not defined.
As the diagnosis of SVCO had been made clinically,
relief from SVCO and any subsequent relapse appears to
have been assessed in the same way. In most studies,
SVCO was described as relieved or not whilst in others,
relief was described as complete or partial. For the
purposes of this review, rates of partial relief were not
included in the analysis. In two studies [12,13] different
scoring systems were used. Whilst a number of studies
described the range of symptoms prior to treatment,
assessment of response was limited to whether SVCO
had been relieved or not. Only one study reported
changes in performance status [14]. There were no other
measurements of symptoms or quality of life.
Objective response rates (determined according to
WHO criteria [15]) were stated in 10/14 chemotherapy
studies or chemotherapy subgroups within studies but
in none of the radiotherapy studies or radiotherapy
subgroups within studies.
Survival data were reported for 19/24 of the
chemotherapy/radiotherapy studies and 13/23 stent
studies.
Adverse event reporting
Whilst almost all studies reported major morbidity, the
reporting of treatment morbidity was, in general, poor.
Neither chemotherapy nor radiotherapy studies used
formal scales (e.g. WHO or RTOG) for adverse event
reporting. In general there was detailed reporting
of morbidity in the stent studies although no formal
grading system was used.
Results
Randomized trials
One randomized trial [9] represented a subset of 37
patients with SVCO in a trial of 366 patients receiving
chemotherapy for small cell lung cancer (SCLC) ran-
domized to receive or not to receive consolidation
thoracic radiotherapy. There was no significant benefit
from thoracic radiotherapy on subsequent recurrence of
SVCO. All patients received initial chemotherapy for 12
weeks; data regarding the effectiveness of chemotherapy
on SVCO are reported below with data from the non-
randomized studies.
       341

Table 1 – Trials not included in review with reasons for exclusion

Reasons for exclusion

Author (see below for key) Published elsewhere

Chemotherapy/radiotherapy
Adelstein 1988 [46] b
Ampil 1994 [47] e
Armstrong 1987 [48] a
Beck 1990 [49] ad
Bell 1986 [50] bd
Chee 1985 [5] d
Chen 1990 [52] bd
Chen 1995 (NSCLC data only) [11] d
Conlan 1983 [53] abd
Davenport 1978 [54] a
Dessard-Diana 1997 [55] d
Fisherman 1973 [56] a
Gauden 1993 [5] a
Howard 1961 [7] ac
Howard 1967 [57] ac
Hsu 1995 [58] bd
Levitt 1969 (randomized study) [8] a
Little 1985 [59] ad
Lochridge 1979 [60] a
Longacre 1968 [61] c
Mikhina 1988 [62] Motorina 1989 [95]
Nicholson 1997 [13] a
Nogiere 1979 [63] e
Parish 1981 [64] ad
Perez 1978 [65] Armstrong 1987 [48]
Rodrigues 1993 [66] a
Rubin 1963 [67] ac
Sadozye 2000 [68] a
Sakai 1973 [69] a
Salsali 1968 [70] Salsali 1969 [72]
Salsali 1969 [71] acd
Scarantino 1979 [72] a
Schraufnagel 1981 [6] abd
Urschel 1966 [73] ac
Wurschmidt 1995 [44] d
Yellin 1990 [74] af
Stenting
Carrasco 1992 [75] a
Charnsangavej 1986 [76] a
Chin 1996 [77] a
Dyet 1993 [78] Nicholson 1997 [13]
Eng 1993 [79] Shah 1996 [96]
Ferro 1995 [80] a
Furui 1995 [81] a
Gaines 1994 [82] a
Kee 1998 [83] a
Nicholson 1997 [13] a
Oderich 2000 [84] a
Oudkerk 1993 [85] a
Oudkerk 1996 [86] f
Putnam 1988 [87] a
Rosch 1987 [88] Rosch 1992 [27]
Sadozye 2000 [68] a
Tacke 1994 [89] a
Thony 1999 [90] a
Wilhelm 1995a [91] Wilhelm 1995b [97]
Wilson 2000 [92] a
Zollikofer 1992 [93] Antonucci 1992 [98]

Key: a, Studies which included patients with diagnoses other than lung cancer or without histological/cytological
confirmation of a lung cancer diagnosis and in which data relating solely to those with confirmed lung cancer was not available.
b, Inadequate treatment details (no mention of radiation dose or which cytotoxic drugs had been given).
c, Radiotherapy not megavoltage.
d, Data for relief of SVCO incomplete or lacking.
e, Selected long-term survivors.
f, Large number excluded or lost to follow-up.
342  

Table 2 – Incidence of SVCO in lung cancer at diagnosis

Author Number in series Number with SVCO % with SVCO

All subtypes of lung cancer

Chen 1995 [11] 3327 79 2.4
Gauden 1993 [5] 6504 249 3.8
Longacre 1968 [61] 941 57 6.1
Salsali 1969 [71] 4960 210 4.2
Total 15 732 595 3.8
Small cell lung cancer
Chan 1997 [21] 446 50 11.2
Chen 1995 [11] 425 30 7.1
Dombernowsky 1978 [24] 225 26 11.6
Kane 1976 [23] 38 8 21.1
Maddox 1983 [19] 860 56 6.5
Morales 1991 [30] 125 20 16.0
Motorina 1989 [94] 350 44 12.9
Sculier 1986 [20] 643 55 8.6
Tan 1995 [17] 161 20 12.4
Urban 1993 [31] 724 87 12.0
Wurschmidt 1995 [44] 408 43 10.5
Total 4405 439 10.0
Non-small cell lung cancer
Chen 1995 [11] 2902 49 1.7

In the second randomized study [10], [Martins SJ,
personal communication], 34 patients with non-small
cell lung cancer (NSCLC) were randomized to immedi-
ate radiotherapy with synchronous weekly cisplatin or
three cycles of chemotherapy with cisplatin, epirubicin
and vinblastine followed by the same chemo-
radiotherapy schedule. Rates of relief of SVCO and
subsequent relapse and survival were not significantly
different between the two arms and the trial was termi-
nated before the accrual target was reached because of a
greater number of treatment-related deaths in the
chemotherapy arm. Data from the two arms are in-
cluded below with data from non-randomized studies.
Non-randomised studies
Incidence of SVCO
A number of studies (both included and excluded)
quoted the incidence of SVCO at diagnosis in their total
referrals over a period of time (Table 2). For all histo-
logical subtypes of lung cancer, the incidence at presen-
tation was 4.2%. The incidence of SVCO at diagnosis for
SCLC was 10.0% and for NSCLC 1.7%. In one oncol-
ogy centre, SVCO was present in 5.5% of cases of
inoperable NSCLC referred for radiotherapy [16].
Only Chen [11] quoted incidence of SVCO for both
SCLC and NSCLC. Over a five-year period 79 cases of
SVCO were diagnosed, of which 38% were SCLC in a
series of 3327 cases in which only 13% were SCLC. In
areas of the world where SCLC is more common, it
would be reasonable to assume that a patient presenting
with SVCO (thought to be due to lung cancer) is as
likely to have SCLC as NSCLC.
Patient characteristics
Age
Within the included studies, there was a wide age range
(29–88 years) for chemotherapy/radiotherapy studies
(mean age ranged from 56–66 years but was not stated in
eight studies). Within the stent studies age ranged from
37–85 years (mean age ranged from 58–72 years but was
not stated in four studies).
Performance status
Pre-treatment performance status was recorded in only
four chemotherapy/radiotherapy studies [17–20] and
change in performance status after treatment in only a
single case report [18]. No stent study reported perform-
ance status.
Quality of life
Formal measurement of quality of life was not reported
in any study. The symptom scoring system [12] was
confined to thoracic or neurological symptoms believed
to have been related to SVCO – general well-being was
not included.
Response rates
Chemotherapy/radiotherapy: small cell lung cancer
Chemotherapy relieved SVCO in 220 out of 286
patients (76.9%; Table 3). A small number received a
Table 3 – Effectiveness of chemotherapy and radiotherapy versus SVCO in SCLC: relief of SVCO, objective response rate and rate of relapse

Chemotherapy Synchronous chemo-radiotherapy Radiotherapy

Complete Partial Total no. Complete Partial Total no. Complete Partial Total no. Objective response
Author relief relief patients relief relief patients relief relief patients CR+PR SVCO relapse

Chan 1997 [21]a 26 28 16 17 14/45

Chan 1997 [21]b 5 7 25 32 5/39
Chen 1995 [11] 16 20 13 14
Dombernowsky 1978 [24] 24 26 21/26 8/26
Egelmeers 1996 [22] 16 17 0/17
Kane 1976 [23] 7 7 2/7
Maddox 1983 [19] 23 32 5 6 15 17 2/55
Morales 1991 [30] 14 17 14/17 1/17
Motorina 1989 [94] 20 12 32 10 2 12 9/32 1/44
Sculier 1986 [20] 35 48 3 7 32/45 14/55
Slawson 1981 [98] 19 1 20
Sorenson 1997 [14] 35 59
Spiro 1983 [9] 21 10 37 16/37 12/37
Tan 1995 [17] 13 16 11/16 1/16
Urban 1993 [31] 70/87
van Houtte 1980 [43] 15 15 15/15
     

Vinson 1983 [99] 1 1 0/1

Total 220 22 286 15 2 18 142 1 183 188/275 60/359
76.9% 7.7% 83.3% 11.1% 77.6% 0.5% 68.3% 16.7%

Numbers of patients treated with chemotherapy and/or radiotherapy. Rates of relief or relapse are expressed as a percentage of total patients treated.
a
No previous treatment; bPatients previously treated with chemotherapy.
343
344  
synchronous chemo-radiotherapy regime following
which relief of SVCO was seen in 15/18 (83.3%). Follow-
ing radiotherapy SVCO was relieved in 142/183 (77.6%).
In three studies in which no previous treatment had been
given [19–21], radiotherapy relieved SVCO in 34/36
(94.4%) compared with 76/108 (70.4%) where all patients
had previously received chemotherapy [14,21,22].
Broadly similar benefits were therefore seen in all cat-
egories giving an overall rate for all treatments of 77.4%
(377/487).
The objective response rate (complete and partial
responses) to chemotherapy was 68.4% (188/275;
Table 3).
Chemotherapy/radiotherapy: non-small cell lung cancer
Chemotherapy relieved SVCO in 46/78 (59.0%; Table 4)
and radiotherapy relieved SVCO in 104/165 (63.0%).
Synchronous chemo-radiotherapy relieved SVCO in
5/16 (31.3%). Combining the three groups gives an
overall rate of 59.8% (155/259).
Data for objective response rates for chemotherapy
were available only for four patients who all achieved a
complete or partial response (Table 4).
Chemotherapy/radiotherapy: studies with subtypes combined
The results in this group (Table 4) are difficult to
interpret. Of the 32 patients in the three studies in this
category, 14 had small cell. The 90% rate of relief of
SVCO appears at odds with the lower rates seen in the
larger SCLC and NSCLC groups.
Stents
In none of the 23 included studies were results for SCLC
and NSCLC reported separately. SVCO was relieved in
151 out of 159 patients (95.0% overall; range 84.6 –
100%; Table 5). Excluding the 14 studies with fewer than
10 patients, the response rate was 108/115 (93.9%). Kishi
[12] reported an improvement in symptom score from a
mean of 6.7 (maximum individual score 10) to 1.3
following stent insertion.
Rapidity of response
Of those responding to radiotherapy or chemotherapy, a
range of response times (measured from the start of
treatment) were reported. In those studies where both
modalities of treatment were used there appeared to be
no distinction between the two with regards to rapidity
of response. Maddox [19] defined his response rates as
responses occurring within 7 days; Sculier [20] noted
that ‘responses generally occurred within ten days’
whilst Tan [17] and Kane [23] found that all responses
had occurred by 15 days. Dombernowsky [24] noted
that the median time to respond was 14 days and Chan
[21] found that 75% of responses had occurred within
three weeks of starting treatment.
Following stent insertion, relief of headache was ‘im-
mediate’ [25]. Oedema of the face resolved within 24
hours but oedema of the arms of trunk took up to 72
hours to resolve [26,27].
SVCO relapse rates
As with rates of relief, rates of relapse of SVCO follow-
ing radiotherapy and chemotherapy were aggregated by
some authors. This aggregation is appropriate in that
a number of patients with SCLC will have received
consolidation thoracic irradiation on completion of
chemotherapy. Relapse data therefore relate to the
effectiveness of both modalities of treatment whereas
data on SVCO relief relate only to the modality used in
the first weeks of the treatment programme. Of a total of
487 patients with SCLC receiving chemotherapy, radio-
therapy or synchronous chemo-radiotherapy, relapse
data were available in 359 (73.7%). Of these, further
SVCO occurred in 60 (16.7%; Table 3). Relapse data
were available in fewer NSCLC patients (54/259, 20.8%
of those treated); further SVCO occurred in 10/54
(18.5%; Table 3). Relapse occurred 1–16 months after
initial treatment.
Following stenting 17/159 (10.7%) had further SVCO
at intervals ranging from 3 days to 8 months with a
median of approximately 1–2 months. Relapse in
stented patients was frequently due to thrombus within
the stent but tumour ingrowth was also encountered. In
four cases, stent thrombosis developed at the same time
as a jugular catheter was introduced [28] or as endo-
bronchial stenting was carried out [29]. In 13/17 patients,
stent patency was restored by thrombolysis or further
stent insertion. This gives a primary patency rate of
84.3% (134/159) and a secondary patency rate of 92.5%
(147/159).
In studies in which thrombolytics were reported as
having been administered prior to stent insertion, the
relapse rate was 10/63 (15.9%) compared with 7/96
(7.3%) in studies in which thrombolytics had not been
administered prior to stent insertion or use was not
reported. Policies regarding anticoagulation varied: al-
most all operators used heparin at the time of the
procedure. Most of those receiving thrombolytics before
stenting received long-term warfarin. Of those not
treated with thrombolytics, some received warfarin for a
period of months and some received long-term aspirin.
When warfarin was used, none advocated a particular
target range for INR. Although it would appear that
those requiring thrombolysis prior to stent insertion
were at higher risk, it is not possible to conclude whether
a particular policy of subsequent anticoagulation
resulted in fewer stent thromboses.
Survival
Median survival in radiotherapy/chemotherapy studies
ranged from 2–9.5 months (not stated in five studies)
Table 4 – Effectiveness of chemotherapy and radiotherapy versus SVCO in studies with histological subtypes combined and in NSCLC: relief of SVCO, objective response rate and rate of relapse

Chemotherapy Synchronous chemo-radiotherapy Radiotherapy

Complete Partial Total no. Complete Partial Total no. Complete Partial Total no. Objective response
Author relief relief patients relief relief patients relief relief patients CR+PR SVCO relapse

Subtypes combined
Davenport 1976 [100] 15 16 0/16
Tanigawa 1998 [37] 10 10 1/10
Ydrach 1980 [32] 4 6
Total 29 32 1/26
90.6% 3.8%
Non-small cell
Citron 1983 [33] 3 3 3/3 0/3
Durdux 1997 [16] 20 21
Egelmeers 1995 [22] 13 17 4/17
Pereira 1998 [34] 34 56
Pereira 1999 [10] 5 16 3/16
Pereira 1999 [10] 8 18 3/18
Slawson 1981 [98] 34 1 38
Sorensen 1997 [14] 37 89
     

Yeh 1997 [18] 1 1 1/1

Total 46 78 5 16 104 1 165 4/4 10/54
59.0% 31.3% 63.0% 0.6% 18.5%

Numbers of patients treated with chemotherapy and/or radiotherapy. Rates of relief or relapse are expressed as a percentage of total patients treated. Two arms of randomized trial shown
in italics.
345
346  

Table 5 – Effectiveness of superior vena caval stenting for SVCO in lung cancer

Number of patients
Author SCLC NSCLC Subtype not specified Number assessable Relief of SVCO Relapse Number recanalized

Antonucci 1992 [97] 2 2 2 1 0

Crowe 1995 [38] 1 9 10 10 4 4
Dondelinger 1991 [101] 13 13 12 0
Edwards 1992 [39] 1 1 1 0
Edwards 1993 [40] 1 1 1 0
Elson 1991 [28] 1 4 5 5 1 1
Entwisle 1996 [41] 1 1 1 0
Gross 1997 [35] 11 11 11 0
Hennequin 1995 [26] 13 13 12 0
Irving 1992 [25] 15 15 15 0
Kishi 1993 [12] 1 3 4 4 0
Kohler 1995 [102] 1 1 1 1 1
Lindstrom 1991 [103] 1 1 1 0
Rosch 1992 [27] 14 14 14 0
Sawada 1992 [104] 5 5 5 0
Schwartzenberg 1996 [105] 5 5 5 1 1
Shah 1996 [95] 4 4 8 7 0
Solomon 1991 [106] 1 3 4 4 2 2
Stock 1995 [29] 4 8 12 11 3 2
Tanigawa 1998 [37] 4 9 13 11 1 0
Watkinson 1993 [36] 2 1 3 3 0
Wilhelm 1995b [96] 2 12 14 12 1 1
Wilkinson 1995 [107] 1 2 3 3 2 1
Total 22 72 65 159 151 17 13
95.0% 10.7%

and in stent studies from 1.5–6.5 months (not stated in
ten studies).
Treatment morbidity
Chemotherapy/radiotherapy studies
In 12/24 chemotherapy/radiotherapy studies, there
was no mention of treatment morbidity. For patients
treated with chemotherapy, deaths within the first four
weeks were recorded in five chemotherapy studies
(10,17,24,30,31] and two radiotherapy studies [21,32].
Non-fatal cytopenia [17,33] and diarrhoea [33] were
recorded following chemotherapy and dysphagia
following radiotherapy [22]. A transient increase in
symptoms [23] and a transient worsening of dyspnoea
within the first three days [19] were noted in
patients treated with chemotherapy. There were no
reports of worsening symptoms in those treated with
radiotherapy. Steroids were given to all patients in one
study [22] and in a proportion of those in two others
[19,31]. Prescription of steroids was ‘allowed’ in two
studies [10,34] and not mentioned in the remaining 19
studies.
Stent studies
Five early deaths, thought to be unrelated to stent
insertion, were reported [26,29,35].
Transient chest discomfort was reported by some
patients when angioplasty was performed immediately
prior to stent placement [27,29,36].
An estimated 29 patients (in studies containing 63
patients) received thrombolytics prior to stenting (Table
5) and a further 13 patients received prophylactic uro-
kinase following the procedure [37]. In this group of 76
patients, the following side-effects were ascribed to
thrombolytic therapy: two cases with haematoma [38]
and one case each of haemoptysis [38], epistaxis [39],
and melaena and bleeding from puncture sites [40]. One
fatal case of haemoptysis and one case of epistaxis and
bleeding from puncture sites were ascribed to heparin
[38] and one patient on warfarin had a haematemesis
[38]. Probably unrelated to the use of thrombolytics or
anticoagulants were one case of cellulitis [38], one case
of pulmonary oedema that responded to oxygen, diuret-
ics and dopamine [12] and one instance of femoral
venotomy performed for stent retrieval [28].
In the remaining 86 patients, there was one case each
of gross elevation of the right hemidiaphragm for
twenty-four hours following stent insertion [25], SVC
thrombosis, successfully treated with urokinase during a
lengthy procedure [27] and an iliac vein tear producing a
retroperitoneal haematoma and necessitating surgical
repair [26]. Stent migration or shortening was an occa-
sional feature only of earlier designs and reported in one
patient only [41].
      
Concomitant prescription of steroids was not men-
tioned in any stenting study.
Discussion
Effectiveness of chemotherapy and radiotherapy
In SCLC, the objective response rate to chemotherapy
was 68.4%, similar to response rates seen in SCLC in
general [42]. More patients had subjective relief of
SVCO (76.9%) than an objective response, consistent
with some patients having less than a partial response
but relief of SVCO. A smaller number of patients with
NSCLC and SVCO treated with chemotherapy have
been reported and data on objective response were
available in only four patients. In NSCLC in general,
objective response rates with chemotherapy are much
lower than in SCLC (20–40% compared with 50–80%).
It is of interest that rates of relief of SVCO were very
similar for chemotherapy and for radiotherapy in both
cell types; 76.9% and 77.6% respectively in SCLC and
59.0% and 63.0% in NSCLC. This indicates that be-
tween these modalities, it would be reasonable to deter-
mine treatment on the basis of stage and performance
status as for patients without SVCO. Effectiveness was
not clearly related to any particular radiotherapy frac-
tionation schedule of chemotherapy regime. Response to
radiotherapy appeared to be higher if patients had not
received previous treatment (94% vs 70%); whether case
selection in the previously untreated group of only 36
patients contributed to this difference is uncertain.
Brain metastases were reported more frequently in
those with SVCO and SCLC compared to those without
[43,44]. Despite this, median survival in SCLC was 16.1
months with SVCO and 13.7 months in the absence of
SVCO [44]. Chen [11] reported a median survival of
eight months in those with SVCO at diagnosis compared
to seven months without SVCO. Similarly others found
survival to be not significantly affected by the presence
of SVCO [9,30,43]. In contrast, in NSCLC, median
survival was six months in those with SVCO compared
to nine months without [11]. In both SCLC and NSCLC
survival was worse if SVCO was present at diagnosis
than if it developed later [11].
Effectiveness of stenting
From these reports, stenting appears to be the most
effective and rapid treatment for the relief of symptoms.
However, the number of patients is smaller than for
chemotherapy and radiotherapy (159 vs 777) and does
not allow analyses by cell type. The duration of
follow-up (and survival) was shorter than for
chemotherapy/radiotherapy studies although stenting
was frequently used in patients failing to respond to or
relapsing following initial treatment.
In the absence of randomized studies, it is not clear
whether patients in stenting studies were selected in any
347
particular way. Kishi [12] reported that of eleven
patients studied with venous pressure measurement (in-
cluding some with diagnoses other than lung cancer),
only six were suitable for stenting. In a further study,
two patients were not stented because tumour was
growing into the SVC lumen [25]. It is unclear whether
a less formal selection process operated in other series
and whether selection criteria differed between those
prescribing radiotherapy or chemotherapy and those
responsible for stent insertion.
Effectiveness of steroids
Steroids form part of standard management of SVCO
when radiotherapy is used in spite of the absence of
evidence to support their use [1]. In the absence of
evidence of problems from radiation-induced oedema in
thoracic radiotherapy, a randomized trial comparing
routine use of steroids vs no routine use would be
justified. If steroids are to be prescribed, the use of high
doses should be of limited duration.
Relapse-free rates
Chemotherapy and radiotherapy
Assuming that all SVCO relapses in surviving patients
had occurred at the time of reporting (which is unlikely
as follow-up was short in some studies), relapse-free
rates (rates of relief minus relapse rates) give an indica-
tion of the palliative value of that particular interven-
tion. For SCLC, 77% had relief from SVCO but 17%
recurred giving a relapse-free rate of 60% (Table 3). For
NSCLC, 60% had relief but 19% recurred giving a
relapse-free rate of 41% (Table 4).
The study reported by Spiro [9] failed to demonstrate
a reduced risk of SVCO recurrence in patients receiving
consolidation thoracic irradiation. As this was a subset
of a larger trial, it did not possess the statistical power to
detect small differences in SVCO recurrence. A subse-
quent meta-analysis has shown that consolidation tho-
racic irradiation reduces the risk of locoregional relapse
from 50% to 25% [45]. On this basis it would be
reasonable to expect that radiotherapy can reduce the
risk of recurrence of SVCO in SCLC.
Stenting
Stents relieved SVCO in 95% of patients and 11%
recurred during the period of follow-up although in a
high proportion of these, patency was restored. This
SVCO-free rate in excess of 80% compares favourably
with the results of chemotherapy or radiotherapy
although this is at the expense of a small but significant
incidence of complications particularly when thrombo-
lytics are used. There is the concern that with longer
348  
follow-up and less careful cases selection relapse-free
rates may be lower. The need for long-term anticoagu-
lants remains unclear.
Treatment options for the future
Options for the future include stenting all patients at
diagnosis or following a policy of stenting those who fail
to respond to radiotherapy or chemotherapy or who
develop further SVCO following an initial response to
treatment. The evidence suggests greater potential for
benefit from early stenting in NSCLC. If a policy of
stenting treatment failures were to be adopted, it would
be necessary to identify treatment failure as early as
possible in the hope that the extent of thrombus forma-
tion and the need for thrombolytics would be mini-
mized. Although the radiotherapy studies indicated that
most patients show signs of response by 14 days, more
detailed studies would be required to confirm this.
Conclusions
Implications for practice
As there is a need to deliver effective anti-cancer therapy
in both SCLC and NSCLC to maximize survival and to
improve and maintain quality of life, chemotherapy
and/or radiotherapy form the basis of treatment as for
patients without SVCO.
In SCLC, the data support the use of stenting for
relapse of SVCO or persistent SVCO following initial
chemotherapy and radiotherapy.
In NSCLC, the data support both a policy of stenting
for relapsed or persistent SVCO following initial therapy
(provided relapse and persistence can be recognized
without undue delay) and a policy of stenting as part of
initial therapy.
Implications for research
For many patients chemotherapy or radiotherapy are
indicated for other manifestations of their disease. The
need for stenting, on the basis of relapse-free rates, is
greater for NSCLC than for SCLC.
Randomized studies incorporating stenting are re-
quired. In NSCLC, an appropriate design might be
standard therapy (radiotherapy, chemotherapy or both
according to current treatment protocols) with stenting
for persisting or recurrent SVCO vs initial stenting
immediately followed by standard therapy. The princi-
pal end-point would be relief of symptoms and quality
of life. A similar strategy might be applied in SCLC
though the present analysis indicates that the potential
for benefit may not be as great. A randomized trial
with similar end-points is needed also to ascertain the
effectiveness of steroids.
Acknowledgements. The authors are grateful to members of the
Cochrane Cancer Network and the Cochrane Lung Cancer Review
Group for their advice and support and to the BUPA Healthcare
Development Fund, Roy Castle Lung Cancer Foundation, Lilly
Oncology, Zeneca, Ares Serono, Bristol Myers Squibb, Pierre Fabre
Oncology and Schering Plough for financial support. The authors are
grateful to Dr F. von Bueltzingsloewen, Dr K. Hammer and Mr
S. Newcombe for help with translation of papers.
Contributions. NPR and FVG wrote the protocol; NPR carried
out the searches; NPR tabulated and analysed the data and wrote the
text; FVG checked the data and the text, results and conclusions of the
review.
Conflict of interest. The authors are not aware of any conflict of
interest.
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Appendix I 8. #5 or #6 or #7
9. #4 or #8
Search strategy for randomized and non-randomized 10. dexamethasone.tw
trials: 11. prednisolone.tw
I. Search of Cochrane Clinical Trials Register 12. #10 or #11
1. SUPERIOR VENA CAVA 13. #9 and #12
2. OBSTRUCTION or SYNDROME 14. exp radiotherapy/
3. #1 and #2 15. radiotherapy.tw
II. Search MEDLINE using the following strategy 16. radiation therapy.tw
1. exp carcinoma, bronchogenic/ 17. #14 or #15 or #16
2. carcinoma, non-small-cell lung/ 18. #9 and #17
3. carcinoma, small cell/ 19. chemotherapy, adjuvant/
4. #1 or #2 or #3 20. #9 and #19
5. superior vena cava syndrome/ 21. stent.tw
6. superior vena cava syndrome.tw 22. #9 and #21
7. superior vena caval obstruction.tw III. Search EMBASE using a similar strategy

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