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

136s Central Nervous System Tumors
2085 General Poster Session (Board #17H), Sat, 1:15 PM-5:15 PM
The role of fluorescence-guided surgical resection in the combined treatment
of malignant glioma. Presenting Author: Carmine Maria Carapella,
Neurosurgery, Cancer Institute Regina Elena, Roma, Italy
Background: Malignant glioma represents a relevant therapeutic issue and
the value of extensive surgical resection remains debated; recent evidence
suggests that radical removal is associated with better survival. An
interesting tool for identifying tumor tissue and increasing the extent of
surgery is represented by fluorescence-guided resection, taking advantage
of metabolic and structural changes induced by a natural precursor of heme
biosynthetic pathway, 5-amino-levulinic acid (ALA). Methods: The present
experience is related to 32 patients affected by malignant glioma (18 newly
diagnosed: 16 glioblastoma (GBM), 2 anaplastic oligodendroglioma; and
14 recurrent GBM) eligible for fluorescence-guided resection, operated on
in our Institute since fall of 2009. All patients underwent preoperative and
early postoperative MRI, showing contrast enhancing lesions. An oral dose
of 20 mg 5-ALA /kg bw was administered to each patient. Microsurgical
resection was performed by an operating microscope enabled to visualize
the fluorescence. All the patients, as first line treatment, have been
submitted to radiotherapy and chemotherapy; second and in some cases
third line treatments were utilized in recurrent cases. The patients
follow-up ranged from 2 years to 6 months. Results: In more than 90% of
patients tumor tissue showed intraoperative red fluorescence; mainly in
recurrent GBM, when MRI documented heterogeneous lesions with enhancing
areas mixed with non enhancing gliotic scars, fluorescence-guided
surgery allowed a better definition of active tumor, with net margins from
perilesional “healthy” brain. Early postoperative MRI confirmed gross total
resection without contrast enhancement in 80 % of patients. In the present
experience the procedure did not determine any relevant additional
neurological deficit. Considering overall survival of recurrent patients we
obtained a median extension of at least 9.0 months (3 – 16� months).
Conclusions: Fluorescence-guided surgery improves tumor detection and
allows extended resection of malignant glioma, without any relevant impact
on neurological status, resulting helpful mainly in the recurrent setting with
a consistent effect on overall survival.
2087 General Poster Session (Board #18B), Sat, 1:15 PM-5:15 PM
Correlation of survival with tumor antigen expression in patients with newly
diagnosed glioblastoma receiving a multi-epitope pulsed dendritic cell
vaccine. Presenting Author: Surasak Phuphanich, Neuro-Oncology Program,
Cedars-Sinai Medical Center, Los Angeles, CA
Background: This study evaluated the safety and immune responses to an
autologous dendritic cell vaccine pulsed with class I peptides from tumor
associated antigens (TAA) expressed on gliomas and overexpressed in their
cancer stem cell population (ICT-107). These TAA epitodes AIM-2. TRP-2,
HER2 and AIM-2, are also overexpressed on glioblastoma multiforme
(GBM) cancer stem cells. Methods: TAA epitopes included HER2, TRP-2,
gp100, MAGE-1, IL13R�2, and AIM-2. HLA-A1 and/or HLA-A2 positive
glioblastoma (GBM) patients with gross total resection were eligible.
Mononuclear cells from leukapheresis were differentiated into dendritic
cells, pulsed with TAA peptides, and administered intradermally three
times at two-week intervals in the axilla region after a standard treatment
with concurrent temozolomide (TMZ) and radiation therapy for newly
diagnosed (ND-GBM). Results: Twenty-one patients were enrolled with 17
ND-GBM and three recurrent GBM patients and one brainstem glioma.
Immune response data on 15 newly diagnosed patients showed 33%
responders. TAA expression by qRT-PCR showed all patient tumors
expressed at least three TAA with 75% expressing all six. Correlations of
increased PFS and quantitative expression of MAGE1, AIM-2, gp100 and
HER2 were observed. A decrease or absence of CD133 expression was seen
in five patients who underwent a second resection. As of February 1, 2012,
six of 16 ND-GBM patients showed no evidence of tumor recurrence
(44-63 months). Median progressive free survival (PFS) in newly diagnosed
patients was 16.9 months with a two-year PFS rate was 43.8%
(95%CI,19.8-66.0 ). The median overall survival rate (OS) was 38.4
months and a two-year OS was 80.3% (95%CI,58.6-96.7). Conclusions:
Expression of four ICT-107 targeted antigens in the pre-vaccine tumors
correlated with prolonged overall survival and PFS in ND-GBM patients.
The goal of targeting tumor antigens highly expressed on glioblastoma
cancer stem cells is supported by the observation of decreased or absent
CD133 expression in the recurrent areas of gadolinium-enhanced tumor.
2086 General Poster Session (Board #18A), Sat, 1:15 PM-5:15 PM
An investigator-initiated monocentric phase I dose escalation trial of
temsirolimus and irinotecan (TEMIR) in patients with relapsing glioblastoma
multiforme (reGBM). Presenting Author: Max E. Scheulen, Department
of Medical Oncology, West German Cancer Center, University of
Duisburg-Essen, University Hospital Essen, Essen, Germany
Background: Deregulation of the PI3K/AKT pathway has been preclinically
involved in the pathophysiology of GBM. The mammalian target of
rapamycin (mTOR) is an important downstream mediator of PI3K/AKT
signalling. The mTOR-inhibitor temsirolimus (Tem) achieves significant
drug levels in brain. Thus, Tem may be effectively combined with irinotecan
(Iri) which has shown promising results in combination with bevacizumab
in patients (pts) with reGBM refractory to temozolomide (Tmz) in phase II.
Exposure to Tem as well as Iri is substantially reduced in pts receiving
CYP3A4 enzyme-inducing anticonvulsants (CYP3A4-Ind). Methods: TEMIR
is a phase I trial of escalating doses of Tem in combination with Iri in pts
with reGBM refractory to Tmz depending on the cotreatment with CYP3A4-
Ind. In pts without CYP3A4-Ind dose escalation of Tem was performed
according to the “3�3 protocol” from 15 via 20 to 25 mg iv wkly together
with 85 mg/m2 Iri iv wkly. In pts with CYP3A4-Ind the doses of Tem were
30, 40 and 50 mg iv wkly together with 170 mg/m2 Iri iv wkly, respectively.
The determination of the pharmacokinetics (PK) of Tem and its influence
on the PK of Iri and its active metabolite SN38 was performed by validated
RP-HPLC methods with fluorescence detection. Results: Up to now, 14 pts
[4 female and 10 male, median age 47 yrs (range 41-65 yrs), 9 without and
5 with CYP3A4-Ind] have been treated. All 9 pts without CYP3A4-Ind (3
pts on 15, 20 and 25 mg Tem each) are evaluable for safety with only mild
toxicity [highest CTC-grade �2 (gr) per pt]: diarrhea 4 (gr2) and 1 (gr3),
neutropenia 1 (gr3), thrombopenia 1 (gr2), anemia 1 (gr2), pneumonia 2
(gr2), rash 1 (gr2). PK parameters of Iri and SN38 were in agreement with
previously published studies and there was no significant effect of 15 to 25
mg Tem combined with 85 mg/m2 Iri on the PK of Iri and SN38. In 7 pts
evaluable for efficacy there was no remission (RECIST) and median time to
symptomatic and/or MRT progression was 10 wks (7, 9�, 10, 10�, 11,
15, 20 wks). Conclusions: The combination of Tem in standard dose of 25
mg iv wkly with 85 mg/m2 Iri wkly is safe in pts with reGBM without
CYP3A4-Ind. Tem has no significant effect on the PK of Iri and SN38.
2089 General Poster Session (Board #18D), Sat, 1:15 PM-5:15 PM
High-dose chemotherapy (HDC) followed by autologous stem cell transplant
(ASCT) for recurrent/progressive CNS lymphoma. Presenting Author:
Mary Roberta Welch, Memorial Sloan-Kettering Cancer Center, New York,
NY
Background: In two reports by Soussain et al, promising efficacy was
observed in recurrent primary CNS lymphoma with induction cytarabine/
VP-16 (CYVE) followed by HDC-ASCT (busulfan, thiotepa and cyclophosphamide
[BTC]), but significant toxicity, mainly from CYVE, has limited
widespread use. We report our experience with HDC-ASCT with alternative
induction regimens. Methods: Retrospective review of pts with recurrent/
refractory non-Hodgkin lymphoma (NHL) with CNS involvement treated
with HDC-ASCT (2000-present). Results: Seventeen pts met inclusion
criteria: med age� 58 (41-65); 9 were women; med KPS prior to
transplant� 90 (range 70-100). At initial presentation, 10 had primary
CNS lymphoma (ocular: 1); 7 had systemic NHL without CNS involvement;
1 had both systemic and CNS disease. Pts had been heavily pre-treated.
Among those with PCNSL, high dose MTX was used in all pts and WBRT in
4. Two pts had received a previous HDC-ASCT. Among systemic NHL pts,
various regimens were used, mostly R-CHOP(4), but also R-EPOCH (1),
CVP (1), ICE (1) and CODOX-M (1). At CNS recurrence, pts received various
induction regimens prior to HD-ASCT: high-dose methotrexate (MTX)based
chemotherapy (N� 13), cytarabine-based regimens (N�2), and
other (N� 2). All pts achieved a CR or near CR prior to HDC-ASCT.
Harvesting was obtained with G-CSF alone in 9 pts; 8 required plerixafor.
Two pts failed mobilization N�15 received HDC-ASCT. The HDC consisted
of BTC (N�13); 1 received BEAM and 1 received reduced intensity
fludarabine, melphalan and alemtuzumab. Eight pts experienced a grade
III or IV toxicity – most commonly fatigue, febrile neutropenia, and
infection. One previously transplanted pt died from sepsis. With a med
follow-up of 11 months, post-transplant med-PFS has not been reached.
The 12m PFS was 92% (95% CI 56-98). Because no patient has
progressed, the OS was identical to PFS. Conclusions: HDC-ASCT was a
highly effective salvage approach in this population of recurrent/refractory
CNS lymphoma. To reduce the risk of harvesting failure at the time of
recurrence, harvesting stem cells at the time of initial treatment could be
considered in pts with high risk for relapse.
Visit abstract.asco.org and search by abstract for the full list of abstract authors and their disclosure information.