2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

Reference Therapy
proved sparing of normal organs surrounding the tumor/
tumor bed. In addition, four-dimensional treatment
planning now allows a quantitative determination of tumor
motion caused by respiration at the time of simulation and
provides further accuracy and confidence in our treatment
delivery. Expert guidelines recommend that these techniques
be used for thymic malignancies where available. 13 It
needs to be noted that the increased conformality of these
techniques harbors the risk of underdosing the tumor, which
may lead to marginal recurrences. Therefore, a clear set of
definitions and guidelines for the simulation, treatment
planning, and delivery using CRT techniques is necessary.
Recently, the International Thymic Malignancy Interest
Group (ITMIG) has published its first set of guidelines to
increase consistency in how RT is delivered to patients with
thymic malignancies. 14 These may allow a more systematic
approach to determine the best use of RT in thymic tumors.
RT dose
The optimal RT dose has not yet been determined. Most
published studies used between 40 and 70 Gy in 1.8 to 2.0 Gy
daily fractions. One study on thymic malignancies, which
included six patients with thymic carcinoma, found that an
RT dose of 50 Gy or greater was associated with improved
local control. 15 However, this has not been confirmed in
other studies. 12 In general, doses of 45 to 50 Gy for negative/
close margins, 50 to 54 Gy for microscopically positive
margins, and 60 Gy for gross residual disease in conventional
daily fractions of 1.8 to 2.0 Gy are recommended
(National Comprehensive Cancer Network guidelines
v2.2012).
Organs at Risk
The organs at risk for short- and long-term toxicities from
RT for thymic carcinomas include the heart, lungs, esophagus,
and spinal cord. More modern RT techniques, such as
three-dimensional CRT and IMRT, allow better sparing of
these organs at risk without compromising target coverage.
General dosimetric guidelines include a mean heart dose of
less than 26 Gy, mean lung dose 20 Gy or less and V20 at
30% to 35% or less, mean esophageal dose less than 34 Gy,
and Dmax to the spinal cord less than 45 Gy. 14
Systemic Therapy
Table 1. Selected Prospective and Larger Retrospective Series of Patients with Thymic Carcinoma Treated with
Cytotoxic Chemotherapy
Systemic therapy for thymic carcinoma is used in two
clinical scenarios, preoperative treatment and palliative
Prospective or
Retrospective Patients RR (%)
Median PFS/TTP
(months)
Median OS
(months) Comment
18 ADOC/ADOCb R 34 50% 21
19 Cisplatin/irinotecan R 9 56% 8 34
20 CODE R 12 42% 6 46
21 Carboplatin, paclitaxel P 23 22% 5 20 Included type B3 thymoma
22 Carboplatin, paclitaxel P 11 36% 8 23
23 Etoposide, ifosfamide, cisplatin R 4 25%
24 Etoposide, Ifosfamide, cisplatin P 8 25%
25 Doxorubicin, cyclophosphamide, cisplatin, vincristine P 8 75% 19
16 Pemetrexed P 11 0 5
Abbreviations: RR, recurrence rate; PFS, progression-free survival; TTP, time to progression; OS, overall survival; ADOC, doxorubicin, cyclophosphamide, vincristine,
cisplatin; ADOCb, doxorubicin, cyclophosphamide, vincristine, carboplatin; CODE, cisplatin, vincristine, doxorubicin, etoposide.
468
RIELY, HUANG, AND RIMNER
therapy. Given the significance of a complete surgical resection—if
significant tumor response occurs—the probability
of complete surgical resection can be improved. In comparison
with more common diseases, identifying the appropriate
chemotherapy regimen to choose for initial or subsequent
therapy for patients with thymic carcinoma is challenging.
As with surgical and RT data, prior reports of thymic tumor
management have often combined patients with thymoma
and thymic carcinoma into small studies. However, there
are relatively large retrospective series and subsets from
prospective series that provide some data to guide therapy.
Cytotoxic Chemotherapy
All chemotherapy regimens evaluated in thymic carcinoma
have been studied either as part of series evaluating
thymoma or used chemotherapy regimens developed for
thymoma. In general, the combination chemotherapy regimens
most widely evaluated have combined platinum analogs,
anthracyclines, along with other agents (Table 1). For
first-line, platinum-based chemotherapy regimens, the response
rates have ranged between 22% and 75%; however,
the varying chemotherapy regimens, different ways data
were collected, and the small sample sizes limit the conclusions
that can be drawn about individual chemotherapy
regimens. Despite our inability to differentiate individual
regimens, it seems clear that the most commonly used
treatments are cisplatin-based chemotherapy, sometimes in
combination with an anthracycline.
Despite the relatively short median overall survival times
reported, there is a frustrating lack of data to guide use of
second-line cytotoxic therapies for treatment of patient with
thymic carcinoma. The exception is pemetrexed in patients
with previously treated advanced thymic carcinoma; unfortunately,
there were no radiographic responses observed,
but there was a median time to progression of 5 months. 16
This summary of data underscores the need for more prospective
evaluation of the cytotoxic chemotherapies often
used to treat patients with thymic carcinoma.
“Targeted” Systemic Therapies
The absence of high rates of radiographic response and
short progression-free survival associated with cytotoxic
chemotherapy has blunted enthusiasm for further evaluation
of such drugs and more recent studies have focused on
newer targeted therapies, often with preclinical rationales
supporting evaluation of a given drug (Table 2). With two