Annual Meeting Proceedings Part 1 - American Society of Clinical ...

2039 General Poster Session (Board #12B), Sat, 1:15 PM-5:15 PM
Use of a non-coplanar half-beam block on the lower spinal field to decrease
the maximum bowel and cumulative dose in craniospinal irradiation.
Presenting Author: Madeera Kathpal, University of Medicine and Dentistry
of New Jersey, New Brunswick, NJ
Background: To develop and compare a non-coplanar half beam block
technique that can be used in both prone and supine treatment positions
with conventional beam matching for craniospinal irradiation (CSI) in order
to decrease the maximum cumulative dose and dose to the bowel, while
maintaining the therapeutic dose to the spinal axis. Methods: Ten treatment
plans from five patients who underwent CSI were analyzed. The bowel was
contoured en bloc for each patient on their simulation cat scan. Two
different geometric techniques for each patient were planned and analyzed.
The first technique consisted of the conventional method for CSI
utilizing two coplanar beams to cover the entire spinal axis. The other
technique used a non-coplanar half beam block on the lower spinal beam to
exactly match the upper spinal beam’s divergence. Four “featherings”
between the two spinal beams for each technique were still necessary to
minimize under and overdosing which occur at abutting beam fields.
Maximum doses for the plan and the bowel were compared between the two
techniques on the same patient. Results: The maximum bowel dose was
decreased between 10 to 35 percent when the non-coplanar half beam
block was used. The maximum doses for the conventional technique were 5
to 35 percent higher than the plans using a non-coplanar half beam block.
The homogeneity of the dose to the spinal axis was not altered with the use
of the non-coplanar half beam block. Conclusions: Use of a non-coplanar
half beam block to match the two spinal fields in craniospinal irradiation
significantly reduces the maximum dose to the bowel and of the entire plan
possibly resulting in reduced gastrointestinal toxicity while maintaining
therapeutic dose to the spinal axis.
2041 General Poster Session (Board #12D), Sat, 1:15 PM-5:15 PM
Toxicity profile of temozolomide in the treatment of 300 malignant glioma
patients in Korea. Presenting Author: Chae-yong Kim, Department of
Neurosurgery, Seoul National University College of Medicine, Seoul National
University Bundang Hospital, Seoul, South Korea
Background: Toxicity of temozolomide itself has been rarely reported in the
field of neuro-oncology. In an attempt to explore the toxicity profiles of
temozolomide we investigated the records of 300 glioma patients in two
institutions in Korea. Methods: We reviewed the records of 300 glioma
patients who were treated with temozolomide between Jan 2004 and May
2010 at two hospitals of our university at two medical centers in Seoul
National University, Korea. The age range of patients was 17 ~ 84 years old
with its median of 49 years old. Their pathologies were glioblastoma,
anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma,
gliomastosis cerebri, gliosarcoma and others. Temozolomide
was used as only concurrent manner with radiotherapy in 46 patients, as
both concurrent and adjuvant manner in 93 patients, and as only adjuvant
or palliative manner in 161 patients. We classified the side effects by
Common Terminology Criteria for Adverse Events version 3.0(CTCAE).
Results: We found 603 events of side effects of temozolomide. Nonhematolgic
toxicities were most common (n�482). Especially, nausea(n�135),
vomiting(n�110), and anorexia(n�40) were common among all kinds of
toxicities. Hematologic adverse events(n�121), for example, thrombocytopenia(n�43),
anemia(n�33), and neutropenia(n�20) were the second
common toxicities. Some patients suffered from fatigue(n�31). None of
our patient presented fatal Pneumocystis jiroveci pneumonitis. In our
series, 512 cases(84.9%) of toxicity were grade 1 or 2, and 91
cases(15.1%) were grade 3 or 4. Grade 3 or 4 toxicity were 140
cases(15.1%). Only 27 cases(2.9%) presented grade 4 toxicity. There was
no mortality due to temozolomide. Only 4 patients (1.3%) presented
leukopenia, which is different pattern compared with the incidence
reported in prior studies from western countries. Conclusions: Temozolomide
had many kinds of toxicities. However, most of the toxicity was
tolerable. This profile could be used to prevent toxic reactions more
effectively and improve the patient’s quality of life. Furthermore, we could
use these lessons for education of patients during the treatment with
temozolomide.
Central Nervous System Tumors
125s
2040 General Poster Session (Board #12C), Sat, 1:15 PM-5:15 PM
Relationship of cognitive function, quality of life (QOL), and neuroimaging
in primary CNS lymphoma (PCNSL) survivors. Presenting Author: Nancy
Diane Doolittle, Oregon Health & Science University, Portland, OR
Background: Delayed treatment-related neurotoxicity in PCNSL is a significant
problem since improved treatments have increased survival. The study
purpose is to describe and correlate neuropsychologic (NP), QOL and
neuroimaging outcomes as neurotoxicity indicators. Methods: Four centers
in Germany and U.S. prospectively evaluated PCNSL patients (pts) in
complete remission (CR) for 2 yrs or more, treated as shown in the Table.
NP tests evaluated attention/executive function, verbal memory, motor
skills, and QOL (Correa, Ann Oncol 2007). Brain MRI was obtained; the
size of T2 abnormalities was determined using two perpendicular linear
measurements where hyperintensities were largest and the sum of the
measurements was calculated. Differences in total T2 among treatments
were compared using analysis of variance; correlations between total T2
and NP or QOL results were assessed using Pearson’s correlation coefficient
(r). Results: From Feb 2009 to Feb 2011, 80 pts were evaluated (43
male; median age, 59; median KPS, 80). Median follow-up from diagnosis
to evaluation was 5.5 yrs. Total T2 abnormalities were significantly
different among treatments (p � 0.0006). The mean area of total T2 in pts
treated with WBRT was significantly higher and more than twice the mean
of any of the other 3 treatments. Total T2 abnormalities were negatively
associated with NP results ie. attention/executive function, r � -0.38 (p �
0.0006), verbal memory, r � -0.23 (p � 0.042), motor skills, r � -0.28 (p
� 0.016), composite score, r � -0.34 (p � 0.002); and functional/global
QOL (higher total T2 associated with lower QOL). Conclusions: This large
PCNSL series in long-term (LT) CR reveals higher total T2 abnormalities in
pts treated with WBRT, which are associated with poorer cognitive
performance and lower QOL at LT follow-up. Enhanced chemotherapy
results in exciting LT survival and function.
Treatment No. pts Follow-up (median, yrs)
High-dose methotrexate (HD MTX)-based
32 4.5
chemotherapy (CHT) alone
MTX-based intra-arterial CHT with blood-brain
25 12.3
barrier disruption alone
HD MTX-based CHT f/b HDT/autologous stem cell
8 4.5
transplantation (ASCT) alone
HD MTX-based CHT (with/without HDT/ASCT) and WBRT 15 5.6
2042 General Poster Session (Board #12E), Sat, 1:15 PM-5:15 PM
The oral transforming growth factor-beta (TGF-ß) receptor I kinase inhibitor
LY2157299 plus lomustine in patients with treatment-refractory malignant
glioma: The first human dose study. Presenting Author: Analia Azaro,
Medical Oncology, Vall d’Hebron, Barcelona, Spain
Background: Activated TGF-b signaling has been associated with poor
survival in several tumors, including glioma. TGF-b inhibitors are expected
to improve outcome. Part B of this Phase I trial assessed safety, pharmacokinetics,
pharmacodynamics, and antitumor activity of the intermittent
treatment with LY2157299 in combination with lomustine. Methods: After
evaluating safety of LY2157299 monotherapy in part A of the study, 2
cohorts of patients were treated with LY2157299 at 160 or 300 mg/day
with intermittent dosing (each cycle�14 days on followed by 14 days off)
in combination with lomustine at standard dose (100 to 130 mg/m2 every 6
weeks) for �2 cycles. Toxicity was assessed using the Common Terminology
Criteria for Adverse Events, version 3. Results: Twenty-six patients with
glioma (18 WHO Grade IV; 5 Grade III; 3 unspecified grade) were treated
with LY2157299 and lomustine (160 mg/day, n�15; 300 mg/day, n�11).
There were no dose-limiting toxicities. No clinically meaningful cardiotoxicities
were observed. Twenty-one SAEs occurred in 10 patients, all
considered to be related to lomustine and none to LY2157299. Of the 26
patients, 7 had thrombocytopenia (27%), and recovery around weeks 4 to 6
was not impacted by the second cycle of LY2157299. Two patients taking
160 mg/day were treated for �6 cycles, with 1 of the 2 patients showing an
unconfirmed partial response. At the 300 mg/day dose, no responses were
observed; 2 patients were treated for �6 cycles. Co-administration of
lomustine did not alter LY2157299 exposure. Observed exposure of
LY2157299 increased with dose escalation between the 2 cohorts. On Day
7, the variability estimates (coefficients of variation) of exposure and
maximum concentration were slightly higher in presence of lomustine
(58%) when compared with LY2157299 alone (47%) and then again
reduced on Day 14 (53%). Pharmacodynamic results will be reported at a
later date. Conclusions: The 14 days on/14 days off treatment with
LY2157299 did not increase the known lomustine toxicity. Given the
overall safety profile and antitumor effect, LY2157299 is being investigated
in Phase II studies.
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