Tumori, 96: 926-929, 2010

Management of neoplastic pericardial effusions

Sergio Cozzi1, Sergio Montanara1, Annalisa Luraschi1, Paola Fedeli1,
Paola Buscaglia1, Vincenzina Amodei1, Ornella Fossati1, Aldo Gioria1,
Elisabetta Garzoli1, and Gianmarco Ferrari2
1
Struttura Operativa Complessa “Oncologia Medica”, and 2Struttura Semplice “Radioterapia”,
Ospedale Castelli, Verbania, Italy

ABSTRACT

Aims and background. Malignant pericardial effusion and cardiac tamponade are
known complications of many advanced malignancies such as breast cancer, lung
cancer, lymphomas and leukemias. Overall survival is low, due to other metastatic lo-
calizations. The present study evaluated the clinical outcome and prognosis in pa-
tients with advanced cancer with pericardial effusion.
Methods. We studied 7 patients, 4 men and 3 women, with malignant pericardial ef-
fusion, affected by breast cancer (2 patients), lung cancer (adenocarcinoma in 3 pa-
tients, microcytoma in 1 patient), and B-cell non-Hodgkin lymphoma (1 patient). All
patients underwent pericardiocentesis; 3 patients underwent an instillation of
thiotepa.
Results. One terminal patient treated with pericardiocentesis died after only a few
hours. All the remaining patients experienced immediate symptomatic improvement
and no operative complications. At the end of the study period, 2 patients were alive
at 59 and 33 months, respectively, and 4 died of disease progression at 1 to 32 months
(mean, 10.5).
Conclusions. Pericardiocentesis is an active necessary approach, and intrapericardial
treatment with thiotepa was able to reduce pericardial effusion and to prevent its
reaccumulation. The standard treatment of malignant effusion and cardiac tampon-
ade has not yet been defined. Physicians should consider the status and the progno-
sis of each case. Free full text available at www.tumorionline.it

Introduction

Pericardial effusion (PE) and cardiac tamponade (CT) are potential complications
of disseminated malignant diseases. Despite treatment, many patients survive for on-
ly 4-5 months1. Signs and symptoms of CT occur frequently in patients with advanced
cancer treated with chemotherapy. In these patients, overall survival is low due to
Key words: antineoplastic agents,
other metastatic localizations2-4. Post mortem examinations show the presence of
cardiac tamponade, pericardial effu-
histologically proven metastatic involvement of the heart and pericardial metastasis sion, thiotepa.
in 15-30% of cancer patients. Pericardial metastasis have been identified in lung can-
cer (35%), breast cancer (25%), lymphoma (11%) and leukemia (5%) patients4-16. In Correspondence to: Dr Sergio Cozzi,
previously asymptomatic patients, CT was the immediate cause of death in about Struttura Operativa Complessa “On-
cologia Medica”, Ospedale Castelli,
85% of cases16. Successful therapy for patients with pericardial disease can increase
via Fiume 18, 28922 Verbania, Italy.
life expectancy or improve palliation and quality of life. Different methods may be Tel +39-0323-541273,
used to approach malignant PE, but the “gold standard” of therapy has not yet been 0323-541373;
defined4-18. fax +39-0323-541540;
e-mail oncovco@hotmail.com
We present 7 cases of proven malignant PE secondary to disseminated carcinoma
that we treated by pericardiocentesis. Three patients underwent an instillation of Received March 13, 2010;
thiotepa. accepted August 5, 2010.
MANAGEMENT OF NEOPLASTIC PERICARDIAL EFFUSIONS
Materials and methods
From 2000 to 2008 in our Division, 7 patients with a
history of PE were analyzed. In all patients, clinically
significant malignant PE developed with symptoms and
signs of CT. All patients had disseminated neoplastic
disease when tamponade developed. The diagnosis of
CT was based on clinical examination, electrocardio-
gram and chest X-ray and was confirmed by echocar-
diography. In all patients, cytopathologic examination
of the PE proved the presence of neoplastic cells in the
pericardial fluid. Survival was calculated from the date
of pericardiocentesis to the date of death. None of our
patients had a history of cardiovascular disease.
Breast cancer was the primary neoplasm in 2 patients,
non-small cell lung cancer in 3 patients, and the re-
maining patients were affected by non-Hodgkin lym-
phoma (1 patient) or small-cell lung cancer (1 patient).
Four patients were receiving systemic chemotherapy at
the time of the procedure. Clinical characteristics are re-
ported in Table 1.
In all patients, pericardiocentesis was performed per-
cutaneously under echocardiographic and ECG moni-
toring. Intracavitary treatment was carried out in 3 pa-
tients on the day (day 1) following further pericardial
drainage. It consisted of a 15 mg bolus of thiotepa and
30 mg of hydrocortisone. On days 3 and 5, we per-
formed further drainage of newly formed fluid, as well
as the administration of the same drugs to a total
amount of 45 mg thiotepa over 3 days. Twenty-four
hours after administering the last dose, the catheter was
removed. All patients underwent further clinical cardio-
logic examinations, ECG, and echocardiogram 30 days
after the initial procedure, and every month thereafter.
Results
The average age when CT developed was 53.1 years.
The mean interval between diagnosis of tumor and de-
velopment of tamponade was 17.4 months (range, 0-
52). All our patients had evidence of metastatic disease
at sites other than the pericardium when the effusion
presented.
Table 1 - Patient characteristics and outcomes
Patient no. Sex Age (yr) Primary Time between diagnosis
tumor & cardiac tamponade (mo)
1 M 46 SCLC
2 F 38 BNHL
3 F 57 BC
4 M 56 NSCLC
5 M 73 NSCLC
6 M 55 NSCLC
7 F 47 BC
M, male; F, female; BC, breast cancer; SCLC, small cell lung cancer; BNHL, B-cell non-Hodgkin lymphoma; NSCLC, non-small cell lung cancer; PC,
pericardiocentesis.
927
In all patients, echocardiographic examination before
pericardiocentesis showed the presence of a uniform
echo-free space, measuring ≥3 cm, around the heart, all
patients showed one or more echocardiographic criteria
of CT (i.e., right atrium and/or right ventricle diastolic
collapse, or the presence of a transmitral Doppler pat-
tern of flow reduction during inspiration). Before un-
dergoing pericardiocentesis, all patients showed a poor
performance status, complaining of weakness, dyspnea
and chest pain (30% of patients). At the ECG, all patients
showed sinus tachycardia, and 3 patients showed low
voltages in precordial leads.
In all the cases, the pericardial fluid was an exudate
containing neoplastic cells, and it was hemorrhagic. All
the patients underwent percutaneous pericardiocente-
sis for therapeutic purposes, and their response was
monitored by following their clinical condition, serial
echocardiograms and chest X-rays.
The treatment was well tolerated, with minimal side
effects. During the procedure, no general or cardiovas-
cular complication was observed, as confirmed by clin-
ical examination, radiograph, ECG (i.e., no arrhythmic
or ischemic events), and echocardiography (i.e., no al-
terations in wall motion or valvular dynamics). Six pa-
tients, after undergoing pericardiocentesis, showed rap-
id and almost complete improvement of symptoms. In 3
patient undergoing instillation of thiotepa, no acute
clinical or ECG alterations were observed; no patient
complained of chest pain or circulatory symptoms. At
the first evaluation (30 days after the initial procedure),
recurrence was not observed in any patient. Clinical ex-
amination revealed no heart failure-related symptoms,
and the echocardiogram did not show any sign of sig-
nificant PE. Treatment with pericardiocentesis plus
thiotepa was performed with the absence of further ef-
fusions. One terminal patient treated with pericardio-
centesis died after only a few hours. Four patients died
of disease progression at 1 to 32 months (mean, 10.5).
At the end of the study period, 2 patients were alive
with no evidence of effusion recurrence: one patient af-
fected by breast cancer, 59 months after undergoing
pericardiocentesis plus thiotepa instillation; one patient
affected by B-cell non-Hodgkin lymphoma, 33 months
after undergoing only pericardiocentesis (Table 1) .
PC PC + thiotepa Status Survival (mo)
0 + - Dead 32
0 + - Alive 33
31.5 - + Dead 7
34 + - Dead 1
4 - + Dead 2
0 + Dead 0
52 - + Alive 59
928
Discussion
Malignant PE and CT are common complications in
patients with neoplastic diseases. The accumulation of
fluid in the pericardial space in patients with cancer is
often not recognized until CT develops. The possible
therapeutic options vary from systemic chemotherapy
to pericardiocentesis, surgical pericardial evacuation,
or mixed procedures. Pericardiocentesis is an emer-
gency life-saving procedure, but it can be associated
with an incidence of PE recurrences near 40%18,19. Local
intrapericardial chemotherapy with different agents,
such as bleomycin, cisplatin, nitrogen mustard, fluo-
rouracil, teniposide, thiotepa, or even radionuclides,
has been studied20-26.
Pericardiocentesis can alleviate CT and yield the diag-
nosis with cytology examination. The procedure is easy
and safe when performed with transthoracic echogra-
phy. The fluid reaccumulates after pericardiocentesis
unless further definitive treatment is started; alterna-
tives include the insertion of a pleuropericardial win-
dow, total or partial pericardiectomy, external radio-
therapy, local instillation of a chemotherapeutic agent,
local instillation of a sclerosing agent, and systemic
chemotherapy27-31.
Thiotepa, an alkylating and sclerosing agent, has been
used for many years in the treatment of solid tumors and
malignant effusions. Thiotepa instillation is not associat-
ed with significant local or systemic side effects32,33. Press
and Livingston18, in a review of documented reports of
malignant PE and tamponade, noted that no definitive
conclusion can be made about optimal management be-
cause there are no controlled trials, and many series are
small with heterogeneous distribution of tumor types,
varying criteria for clinical response and concurrent
treatments. Reynolds and Byrne31 advocated pericardio-
centesis followed by systemic chemotherapy for malig-
nant PE in carcinoma of the breast. Local control of PE
was achieved and survival was extended, but their sur-
vival data were incomplete. Bitran et al.19 managed their
patients with a pleuropericardial window and systemic
chemotherapy. They achieved a median survival of 26
months (range, 17-50). Direct comparisons are difficult.
Establishment of a pleuropericardial window may not be
necessary because none of our patients had evidence of
recurrence of PE at the time of death. Smith et al.34, in a
review of all reported cases of malignant PE up to 1974,
concluded that patients treated conservatively without
surgical intervention had a longer symptom-free interval
than those given a pericardial window. A few studies al-
ready have been reported regarding thiotepa effective-
ness in the treatment of malignant PE. The work of
Bishiniotis et al.35 showed better overall results but was
conducted only in women with breast cancer, a particu-
lar population with a longer median survival.
Although the survival of patients with neoplastic CT is
in general limited, we believe that an active approach is
S COZZI, S MONTANARA, A LURASCHI ET AL
necessary. Our study shows that there does not seem to
always be a predilection for CT in patients with advanced
disease. In fact, in 2 patients with concealed cancer dis-
ease it was the very first symptom. Pericardiocentesis can
achieve significant palliation, control PE, prolong sur-
vival with minimal toxicity, and give a good quality of life.
We concluded that the aggressive treatment of malignant
PE, when possible associated with local chemotherapy,
results in a better quality of life and a longer life ex-
pectancy, with the absence of significant side effects. Ac-
cordingly, PE should not be considered as a terminal
event but as a treatable condition requiring a true thera-
peutic intervention instead of a mere palliative approach.
For patients with long life expectancy, the therapy must
be used to relieve symptoms and to prevent PE.
Pericardiocentesis associated to intrapericardial scle-
rotherapy with thiotepa is the best compromise in
terms of recurrence prevention, tolerability and costs
and can be considered as a first-choice procedure in ap-
proaching the treatment of patients with neoplastic PE.
Real randomized, case-control studies are moreover re-
quired to assess the gold standard of malignant PE treat-
ment, in the absence of standardized case-control trials
and for the heterogeneity of oncologic patients36. Physi-
cians should consider the status and the prognosis of
each case. The choice of an appropriate therapy may be
difficult, and the optimal management remains actual-
ly controversial.
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