2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

MANAGEMENT OF THYMIC CARCINOMA
recurrence rate, and shorter survival relative to patients
with thymoma. Thymic carcinoma rarely presents at an
early stage. A small, well-encapsulated thymic carcinoma is
an uncommon occurrence and would likely only be diagnosed
after being resected. More typically, thymic carcinoma presents
in a locally advanced setting, with evidence of local
invasion, adenopathy, or pleural or pericardial involvement.
In a recent series at our institution, 75% of thymic carcinomas
presented as Masaoka stage III or IV. 4
In patients who present with locally advanced disease,
achieving a complete resection is often difficult. Within the
anatomic confines of the mediastinum, the ability to obtain
a clear surgical margin is frequently limited by the great
vessels of the heart. Published complete resection rates vary
from 20% to 60%, and our institutional complete resection
rate of 52% is consistent with these results. 4-6 Extended
resections involving resection of the innominate vein or
superior vena cava can be done in appropriate settings. In
one series, one-third of the patients required partial or
complete resection of the vena cava. 7 Circumferential resection
of the vena cava also necessitates resection of the
phrenic nerve, and careful assessment of pulmonary function
in the preoperative planning is mandatory, with consideration
given to diaphragm plication at the time of surgery
if indicated. It is debatable whether a tumor that invades
the aorta, pulmonary trunk, or a cardiac chamber can still
be resected. Although these situations may be technically
feasible with the use of cardiopulmonary bypass, there is no
data to suggest that the outcomes would be better than the
alternative of debulking and R1 resection followed by radiotherapy
for the residual disease. 7 There is insufficient evidence
of benefit to support the added morbidity and risk of
such measures.
There is no consensus regarding the role of mediastinal
lymph node dissection for patients with thymic carcinoma.
Patients with thymic carcinoma much more frequently
have nodal involvement than those with thymoma. 8 Any
clinically involved nodes must be resected en bloc with the
specimen, and a careful search of the mediastinum should
entail the prevascular, aortopulmonary, internal mammary,
and cervical stations. Whether a systematic mediastinal
lymphadenectomy—including subcarinal and paratracheal
stations—is warranted is unclear and must be individualized
to the patient. 9
Local invasion of the lung is common and can be fre-
KEY POINTS
● Thymic carcinomas are an uncommon subset of thymic
tumors.
● There are limited prospective data regarding treatment.
● The outcomes of patients with thymic carcinoma are
worse than that seen with thymoma.
● In localized thymic carcinoma, complete surgical resection,
if possible, should be performed.
● Radiation therapy may be used as adjuvant therapy
after surgical resection or as the definitive treatment
modality in patients with localized thymic carcinoma
that is deemed unresectable.
quently managed with wedge resections or lobectomy if
necessary. Individual pleural metastases can be easily resected
in some circumstances. However, pleural involvement
that presents as innumerable miliary metastases, or
conversely, as bulky confluent disease will preclude complete
resection. Extrapleural pneumonectomy has been advocated
for stage IVa thymoma by several institutions
including our own, but the poorer prognosis for patients with
thymic carcinoma and the morbidity associated with the
procedure engenders less enthusiasm for this aggressive
approach. 7,10
RT
Although surgical resection remains the most important
component in the management of all thymic tumors, RT
may be used as adjuvant therapy after surgical resection or
as the definitive treatment modality in patients who are
deemed unresectable because of medical comorbidities or
technical reasons. No prospective trials have established a
clear role for RT, but a series of retrospective studies have
demonstrated that excellent local control rates can be
achieved when surgical resection and RT are combined.
The largest study was reported by Kondo et al. 8 Onehundred
and eighty-six patients with thymic carcinoma at
multiple institutions had surgically excision and treatment
with adjuvant chemotherapy, RT, both, or no adjuvant
therapy. Fifty-one percent of patients had undergone a
complete resection. The most important prognostic factor
for overall survival was a complete resection. Nevertheless,
51% of patients developed a recurrence. Although RT improved
the results in incompletely resected tumors, there
was no clear benefit in patients who had undergone a
complete resection.
Similarly, a retrospective study of 40 cases with long-term
follow-up (median follow-up time of 87 months for surviving
patients) found that a complete resection was the most
important prognostic factor on multivariate analysis. 11 All
patients in this study were treated with either adjuvant RT
in resectable patients or definitive RT in unresectable cases.
They achieved 100% in-field local control in 16 patients who
underwent a complete resection followed by adjuvant RT
with a median dose of 50 Gy. Other significant prognostic
factors included a KPS of 70% or greater and low-grade
histology. The 5- and 10-year overall survival rates for the
whole patient group was 38% and 28%, respectively.
Hsu et al reported their experience of 26 patients with a
minimum follow-up of 40 months, all of which were treated
with adjuvant RT at a median dose of 60 Gy after a total
or subtotal resection. 12 Excellent 5-year local control rates
of 92% after a complete surgical resection and adjuvant RT
were obtained. Even after an incomplete resection and
adjuvant RT, 5-year local control rates of 88% were
achieved. The 5-year overall survival in this study was 77%.
RT techniques
Most published studies to date have reported outcomes on
patients who were treated over a long period of time with
often times old two-dimensional RT techniques using opposed
fields. However, the development of more conformal
RT (CRT) techniques—such as three-dimensional CRT in
the early 1990s and more recently intensity-modulated RT
(IMRT) or proton therapy—has allowed significantly im-
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