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

5042 General Poster Session (Board #18B), Sun, 8:00 AM-12:00 PM
Detection of disseminated tumor cells in bone marrow as an independent
prognostic factor in primary ovarian cancer patients. Presenting Author:
Pauline Wimberger, AGO and Department of Gynecology and Obstetrics,
University of Duisburg-Essen, Essen, Germany
Background: Detection of disseminated tumor cells (DTC) in the bone
marrow (BM)of breast cancer patients is associated with poor outcome.
Recent studies demonstratedthat DTC may serve as a prognostic factor in
ovarian cancer.The aim of our study was to evaluate the impact of BM
status on survival in a large cohort of ovarian cancer patients. Methods: 365
patients with primary ovarian cancer were included into this three-center
prospective study. BM aspirates were collected preoperatively from iliac
crest. Disseminatedtumor cells were identified by immunocytochemistry
using the pancytokeratin antibodyA45B/B3 and by cytomorphology. Patient
outcomes were evaluated using a multivariable Cox regression model.
Results: Disseminated tumor cells were detected in 28% of all BM
aspirates. The number of CK-positive cells ranged from 1 to 42 per 2x106 mononuclear cells. DTC status did not correlate with any of the established
clinicopathogical factors. The overall survival was significantly shorter
among DTC-positive patients compared to DTC-negative patients (51 mo,
95% CI: 35 – 67 mo versus 32 mo, 95% CI: 22 – 42 mo; p � 0.003).
However, disease-free survival was not related to DTC-positivity. In the
multivariable analysis, BM status, FIGO stage, nodal status, resection
status and age were independent predictors of reduced overall survival.
Interestingly, a subset of DTCs may have stem cell properties since a subset
of these cells (128 out of 228 cases) were SOX2 positive, which is an
embryonic stem cell marker. Conclusions: Tumor cell dissemination into
bone marrow is a common phenomenon in ovarian cancer. DTC detection
has the potential to become an important biomarker for prognostication and
may be included as a therapeutic target in future concepts.
5044 General Poster Session (Board #18D), Sun, 8:00 AM-12:00 PM
What do 676 primary and recurrent ovarian cancer (OC) patients expect
from their doctors and therapy management? Results of a German survey of
the northeastern German Society of Gynecological Oncology (NOGGO).
Presenting Author: Gülten Oskay-Özcelik, NOOGO, Berlin, Germany
Background: The primary aim of this study was to investigate information
needs and preferences among patients with ovarian cancer, focusing
especially on doctor-patient relationships and therapy management.
Methods: A 42-item questionnaire was developed and validated in a
mono-centre phase I study and was then provided to primary and recurrent
ovarian cancer patients via internet (online) or as a print-version. In the first
part basic data (age, tumour status, therapy) were requested. In the second
part, most of the questions try to evaluate the expectations and needs
concerning their therapy management and doctor-patients communication.
Results: From January to November 2009, a total of 676 (201 online; 475
print version) patients with ovarian cancer from 44 German centres took
part in the survey.The median age of the online group was 49 years (range
19-84), for the print group 62 years (26-92). Nearly all patients (98.7%)
had a primary surgery and a primary chemotherapy (89%). Asked for side
effects during therapy, the most frequent answers were alopecia, paraesthesia/dysaesthesia
and fatigue. Most of the patients were content with the
completeness and understandability of the explanations about the therapies
from their doctors . The three most important aspects, which were
proposed by patients to improve therapy against ovarian cancer were:
“Doctors should have more time for explanations”, “The therapy should not
lead to any loss of hair”, and “The therapy should be more effective”.
Conclusions: This study underlines the high need of ovarian cancer patients
to discuss all details concerning treatment options and clinical management.
As matter of fact, the physician involved in the treatment is the most
important source of information.
Gynecologic Cancer
337s
5043 General Poster Session (Board #18C), Sun, 8:00 AM-12:00 PM
BRCA1 immunohistochemistry in high-grade serous ovarian cancers
(HGS-OC) characterized for BRCA1 germ-line mutations. Presenting Author:
David Michael Hyman, Memorial Sloan-Kettering Cancer Center, New
York, NY
Background: The optimal use of BRCA1 germline testing in patients with
HGS-OC is unclear. Moreover, BRCA1 germline testing does not provide
information on non-germline mechanisms of BRCA1 loss. We investigated
the performance of BRCA1 immunohistochemistry (IHC) testing in HGS-OC
with known BRCA1 mutation status. Methods: Eligible patients had
HGS-OC, underwent surgery at a single institution between 1997 and
2010, and were tested for germline BRCA1 mutations under IRB-approved
protocols. FFPE tumor tissue was used in triplicate to construct a tissue
microarray (TMA). Two pathologists, blinded to BRCA1 status, independently
scored each sample as BRCA1 IHC present (normal) or absent
(abnormal). Whole sections were stained for all samples with absent
BRCA1 staining on TMA. A commercially available monoclonal antibody
against BRCA1, clone MS110 from Calbiochem (OP92) was used with
previously optimized conditions. Results: 123 samples (30 BRCA1 �; 93
BRCA1 wild-type) were analyzed and 47 (38%) had abnormal BRCA1 IHC.
Inter-observer agreement on BRCA IHC was high (kappa�0.87). BRCA IHC
had a sensitivity of 83.3% (CI: 70.0-96.7%), specificity of 76.3% (CI:
67.7-85.0%), PPV of 53.2% (CI: 38.9-67.5%), and NPV of 93.4% (CI:
87.9-99.0%) for BRCA1 germline mutation. There was a trend towards
improved overall survival in the BRCA IHC abnormal vs. normal patients
(median survival 82 vs 61 wks, HR 0.70, p�0.12). Conclusions: BRCA1
IHC is a reproducible and inexpensive test with a high NPV for absence of a
BRCA1 germline mutation. The 22 (17.7%) cases with abnormal BRCA1
IHC and wild-type BRCA1 germline status may have other mechanisms of
protein loss such as promoter hypermethylation or somatic mutation and
are currently being tested for these changes. This rate of non-germline
BRCA1 loss in HGS-OC is consistent with data generated by the Tumor
Cancer Genome Atlas Network. BRCA1 IHC may be useful as a reliable
biomarker for risk stratification in HGS-OC.
Germline BRCA1 status
Wild-type Mutated
BRCA1 IHC
Normal 71 (57.2%) 5 (4.0%)
Abnormal 22 (17.7%) 25 (20.2%)
5045 General Poster Session (Board #18E), Sun, 8:00 AM-12:00 PM
Correlative study of low serum creatinine and hematological toxicities in
Japanese patients with ovarian cancer treated by dose dense TC therapy.
Presenting Author: Koji Matsumoto, Medical Oncology Division, Hyogo
Cancer Center, Akashi, Japan
Background: Dose dense TC (ddTC) is a novel standard therapy for patients
(pts) with advanced ovarian cancer, although hematological toxicities
(hemTX), especially anemia, may increase as observed in NOVEL trial
(JGOG3016). Low serum creatinine (LCr), especially below 0.7 mg/dl, may
lead to overestimation of GFR. GOG announced that pts with LCr should use
a minimum value of 0.7mg/dl to estimate GFR. The correlation between
LCr and hemTX treated by ddTC is unknown. Methods: GFR was determined
using the Cockcroft-Gault formula. Serum creatinine concentrations were
measured using enzymatic assays. Minimum value of 0.7 mg/dl was not
used during this period of time. The carboplatin clearance was then
calculated by Calvert equation. HemTX were defined as, Grade 3 or 4 (by
CTC-AE ver.4) neutropenia, anemia, and thrombocytopenia. Using electrical
chart, frequency of hemTX and correlation between serum creatinine
(less than 0.7 or not) were examined. Results: From Feb. 2010 to Dec.
2011, 61 consecutive pts were treated with ddTC. LCr was observed in
73% of pts. No treatment related death occurred. Among 61 pts, 50
(82%), 31 (51%), and 12 (19.6 %) pts experienced Grade3/4 neutropenia,
anemia and thrombocytopenia, respectively. HemTX in pts with LCr and the
others were as in the Table. Conclusions: LCr is frequent in Japanese female
pts. ddTC in practice setting seems safe, and hemTX of ddTC are similar
with those observed in NOVEL trial. The rationale using a minimum value of
0.7 mg/dl should be further studied by larger population, such as pts in
NOVEL trial.
G3/4 neutropenia G3/4 anemia G3/4 thrombocytopenia
Pts with LCr 36 (80%) 24 (53.3%) 9 (20%)
Pts without LCr 14 (87.5%) 7 (44%) 3 (18.8%)
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