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

2015 Poster Discussion Session (Board #3), Fri, 1:00 PM-5:00 PM and
4:30 PM-5:30 PM
Intraventricular (IVe) topotecan for women with neoplastic meningitis (NM)
associated with �responsive� malignancies. Presenting Author: Kurt A.
Jaeckle, Mayo Clinic, Jacksonville, FL
Background: A prior study of intra-CSF topotecan (TOPO) for unselected pts
w/ NM reported PFS 6 mo of 19%, and OS of 15 wks (Groves, NeuroOncol
2008;10:208). We postulated that greater activity might occur in pts w/
malignancies considered sensitive to topoisomerase inhibitors. Methods:
We reviewed outcome of women with NM and adenocarcinoma of the
breast, ovary or lung receiving IVe TOPO (0.4 mg 2x/wk x 4wk, Q wk x 4, Q
2wk x 2, Q mo x 3, Q 2mo x 3, and Q 3mo x 4) until progression (PROG) or
adverse events (AE). All had baseline CSF cytology, and MRI of brain and
spine. CSF cytology was obtained at each treatment (Rx), and brain/spine
MRI Q 3mo. Neuro-specific PROG was defined as recurrent � CSF cytology;
PROG of NM on MRI; all-cause neurologic worsening; pt refusal; or death.
PFS/OS were measured from 1st TOPO Rx. All pts signed consent; the study
was IRB approved. Results: 17 women (breast -12; lung-3; ovary - 2) were
treated via Ommaya reservoirs; 7 (41%) had VP shunts w/ valves, adjusted
for Rx. Median (med) age was 53 (41-79), and KPS 70 (50-90). At
presentation, 11(65%) had � CSF cytology and 14 (82%) had NM on MRI
[brain-11 (65%); spine-10 (59%)]. 15 (88%) had no prior intrathecal Rx.
13 pts (76%) received focal RT for CNS disease, and 8 (47%), chemotherapy
for extracranial disease. Med.number of Rx were 13/pt (range,
3-50); med. duration of TOPO Rx was 14 wks (range, 1-109). Med.
neuro-specific PFS was 13 wks; PFS6 was 41%, and PFS12, 29 %. Med.
OS was 33 wks (range, 5-180), w/ 4 alive at 13�, 30�, 33�, and 180�
wks. 4 pts (24%) lived � 95 wks. Of 11 w/ baseline � CSF cytology, 7
(64%) cleared CSF of malignant cells (med. duration clear � 47 wk (range,
9-104). AE included arachnoiditis (18%), leukoencephalopathy (18%),
and Ommaya infections (12%). Rx was stopped for neuro PROG (29%);
systemic PROG (23%); refusal (18%); AE (12%); or persistent negative
CSF (6%); 12% are still on Rx. Conclusions: Promising activity of IVe TOPO
was observed in women with NM from breast, lung and ovarian cancer. PFS
6 and 12, OS and cytologic response were twice that noted in prior studies
of NM pts w/ unselected malignancies. This data supports our plan for a
phase II study targeting this select cohort.
2017 Poster Discussion Session (Board #5), Fri, 1:00 PM-5:00 PM and
4:30 PM-5:30 PM
Modeling radiation dose to circulating lymphocytes during brain tumor
treatment: Effects of target volume, dose rate, and treatment technique.
Presenting Author: Susannah G. Yovino, Johns Hopkins University School
of Medicine, Baltimore, MD
Background: Severe treatment-related lymphopenia (TRL) occurs in 40% of
glioblastoma patients despite minimal radiation (RT) doses to bone marrow
or nodal sites. In glioblastoma, TRL is associated with decreased survival.
To explain the lymphopenia, we sought to estimate radiation doses received
by circulating lymphocytes during partial brain RT. Methods: An in-house
computer program linked to treatment planning software was used to
calculate the mean radiation dose to circulating blood (DCB) and the
fraction of blood receiving �0.5 Gy. The model also studied the impact of
different target volumes (PTV), dose rates (DR), and delivery techniques
(IMRT, 3D-CRT). Results: The mean DCB for a 60-Gy course (8-cm
diameter PTV, dose rate 600 MU/minute) was 2.2 Gy. With this the entire
blood pool receives a lymphotoxic dose of �0.5 Gy. DCB is correlated with
fraction number, PTV size, and DR. Regardless of dose rate or delivery
technique, the percent of circulating blood receiving �0.5 Gy approached
100% as the number of fractions increased. Changing dose rate had
minimal effects on mean DCB (3.1Gy for 300 MU/min vs 2.2 Gy for 1200
MU/min). Smaller PTV size reduced the percent of blood receiving �0.5 Gy
(15% for 2-cm diameter PTV vs 100% for 8-cm PTV). Conclusions:
Standard RT for brain tumors delivers a lymphotoxic radiation dose to
circulating blood. Altering dose rate may initially affect DCB, but advantages
disappear over the course of 30 fractions. Marked reductions in target
size appear to be the best way to avoid radiation injury to normal circulating
lymphocytes. Other novel approaches are needed to limit radiation exposure
to circulating lymphocytes given evidence associating lymphopenia
with poorer outcomes in cancer patients.
Central Nervous System Tumors
119s
2016 Poster Discussion Session (Board #4), Fri, 1:00 PM-5:00 PM and
4:30 PM-5:30 PM
Addition of upfront whole-brain radiotherapy to surgery or stereotactic
radiosurgery versus surgery or stereotactic radiosurgery alone for treatment
of brain metastases: A systematic review and meta-analysis. Presenting
Author: Yu Yang Soon, National University Cancer Institute, Singapore
Background: The benefits of adding upfront whole-brain radiotherapy
(WBRT) to surgery or stereotactic radiosurgery (SRS) when compared to
surgery or SRS alone for treatment of brain metastases are unclear. We
performed a systematic review and meta-analysis of published randomized
controlled trials (RCT) to determine the efficacy and safety of additional
upfront WBRT. Methods: We searched MEDLINE, EMBASE, CENTRAL
from date of inception and annual meeting proceedings of ASCO and
ASTRO from 1999 to September 2011 for RCTs comparing surgery or SRS
plus WBRT with surgery or SRS alone for treatment of brain metastases.
The primary outcome was overall survival (OS). Secondary outcomes
include progression free survival (PFS), local and distant intracranial
disease progression, neurocognitive function (NF), quality of life (Qol) and
neurological toxicity. Hazard ratios (HR), confidence intervals (CI), p values
(p) were estimated with random effects models using Revman 5.1. Results:
We found five RCTs including 663 patients with one to four brain
metastases. Adding upfront WBRT decreased the one-year incidence of any
intracranial disease progression from 73-76% to 22 - 47% but did not
improve OS (HR 1.11, 95%CI 0.83 - 1.48, p � 0.47) and PFS (HR 0.76,
95%CI 0.53 - 1.10, p � 0.14). Subgroup analyses showed that the effects
on overall survival are similar regardless of types of focal therapy used,
number of brain metastases, dose and sequence of WBRT. The effects of
upfront WBRT on NF, Qol and neurological toxicity were variable.
Conclusions: Adding upfront WBRT to surgery or SRS significantly decreased
any intracranial disease progression at one year but did not improve
overall and progression free survival and produced variable effects on
neurocognitive function, quality of life and neurological toxicity when
compared with surgery or SRS alone. Future research should focus on
developing more effective approaches to characterize and ameliorate the
potential neurological toxicity of WBRT.
2018 Poster Discussion Session (Board #6), Fri, 1:00 PM-5:00 PM and
4:30 PM-5:30 PM
Phase II trial of sunitinib as adjuvant therapy after stereotactic radiosurgery
(SRS) in patients with 1-3 newly diagnosed brain metastases. Presenting
Author: David M. Peereboom, Cleveland Clinic, Cleveland, OH
Background: For patients with 1-3 brain metastases, standard therapy after
SRS is adjuvant whole brain radiotherapy (WBRT). SRS without WBRT
carries a higher rate of brain relapse. Due to concerns about neurologic
sequelae of WBRT, however, many patients and physicians opt to defer
WBRT until the time of central nervous system (CNS) progression. This trial
used sunitinib as an alternative to WBRT for post-SRS adjuvant therapy.
Sunitinib inhibits vascular endothelial growth factor signaling, and we
hypothesized that it would prevent growth of microscopic brain metastases
presumed to be present. The objective was to use adjuvant sunitinib after
SRS to prevent the emergence of new or progressive disease in the brain or
at the site of SRS and to preserve neurocognitive function. Methods:
Eligible patients had 1-3 newly diagnosed brain metastases, RTOG RPA
class 1-2, and started sunitinib � 1 month after SRS and baseline
neuropsychological testing (NPT). Patients with controlled systemic disease
were allowed to continue chemotherapy for their primary disease
according to a list of published regimens (therapy � sunitinib) included in
the protocol. Patients received sunitinib 37.5 or 50 mg/d days 1-28 every
42 days until CNS progression. NPT and MRIs were obtained every 2
cycles. The primary endpoint was the rate of CNS progression at 6 months
(PFS6) after SRS. Results: Fourteen patients enrolled. The median age was
59 (range 46-80). Main histologies: lung 36%, breast 21%, melanoma
14%. Toxicities: Grade 4: neutropenia [ANC] (1 pt); Grade 3: fatigue (5),
ANC (2), rash (1). Dose reduction due to toxicity: 1 pt (to 37.5 mg/d). The
CNS PFS6 and PFS12 were 50% � 13% and 43% � 13%, respectively.
The median PFS was 6.6 months (95% C.I. 1.5-19). NPT results will be
reported at the meeting. Conclusions: Sunitinib after SRS for 1-3 brain
metastases was well tolerated with a PFS6 of 50%. The use of novel agents
to prevent progressive brain metastasis after SRS requires the incorporation
of chemotherapy regimens to control the patient’s primary disease.
Future trials should continue to explore the paradigm of secondary
chemoprevention of brain metastases after definitive local therapy (surgery
or SRS).
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