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Annals of Oncology
Conclusions: Treatment with long-acting somatostatin and having multiple surgeries
were shown to be independent predictors of improved overall survival in NETs. This
data further supports the use of aggressive medical and surgical intervention in a
multi-modal approach for advanced NETs. This may be best achieved in the setting
of NETs multidisciplinary reference centres.
Disclosure: All authors have declared no conflicts of interest.
1168P DOES SPECIALIST CENTRE HISTOPATHOLOGY REVIEW
OF GASTROINTESTINAL NEUROENDOCRINE TUMOURS
AFFECT CLINICAL MANAGEMENT?
S.C. Bowen Jones, L. Foster, J. Valle, W. Mansoor, R. Hubner, B. Chakrabarty
Histopathology, The Christie NHS Foundation Trust, Manchester,
UNITED KINGDOM
Introduction: Gastroenteropancreatic Neuroendocrine Tumours (GEP NET) are
uncommon tumours occurring at all sites within the gastrointestinal tract. The
behaviour of these tumours is difficult to predict and they have been subject to
numerous changes in classification and grading systems. In the UK the National
Institute for Clinical Excellence recommends centralised histopathology review of
these tumours by a member of the NET tumour board. We aimed to determine the
frequency of discrepancies between local and central histopathology that could
impact clinical management.
Methods: We identified 86 cases of suspected GEP NET referred for specialist
histopathology review at the regional network centre from January 2010 to April
2012. Cases were identified by a SnoMed search for cases coded under various
endocrine tumour designations and by cross referencing with patient lists from
multidisciplinary team meetings. Details of the local and network centre pathology
reports were compared. The reports were also judged for compliance with the UK
Royal College of Pathologists minimum dataset.
Results: There was complete diagnostic agreement in 54 cases (63%). Discrepancies
occurred in the remaining 32 cases (37%), including, 18 differences in grade or
proliferation index score (21%), 16 differences in nomenclature (19%), 6 differences
in stage (7%) and 5 differences in assessment of perineural or vascular invasion (6%).
In 9 cases (10%) an original diagnosis of endocrine tumour was changed to a
different type of tumour without endocrine differentiation or vice versa following
review. Twenty-six of the overall discrepancies (30% of the total cases) had the
potential to meaningfully impact on clinical management. In addition, neither
tumour grade nor proliferation index were recorded in 15 local pathology reports
(17%), which would necessitate additional pathological analysis prior to clinical
decision making. There was full adherence to the minimum dataset in only 19 cases
(42% of resections).
Conclusions: This study highlights the importance of specialist centre histopathology
review of GEP NET to ensure these patients receive the appropriate clinical
management.
Disclosure: All authors have declared no conflicts of interest.
1169P NOVEL INFLAMMATION-BASED PROGNOSTIC
DETERMINANTS IN PATIENTS WITH CARCINOMA
OF UNKNOWN PRIMARY
Z. Mohamed, D.J. Pinato, R. Sharma
Division of Experimental Medicine, Imperial College London, Hammersmith
Hospital, Hammersmith, UNITED KINGDOM
Background: Carcinomas of unknown primary (CUP) incorporate tumours with
heterogeneous biology and invariably poor prognosis. There is a lack of validated
prognostic indices in this context. The presence of a cancer related systemic
inflammatory reaction is both pathogenic and prognostic in advanced cancer. We
aimed to assess whether a panel of inflammatory indices including the
modified-Glasgow Prognostic Score (mGPS), neutrophil/lymphocyte ratio (NLR) and
platelet/lymphocyte ratio (PLR) could predict prognosis and response to therapy in
CUP.
Methods: Consecutive patients diagnosed with histologically proven CUP at the
Imperial College oncology unit (1996-2011) were considered. Demographic,
treatment, disease status and bloods were collected. The effect of candidate
prognostic factors on overall survival (OS) was determined using Kaplan-Meier
curves followed by multivariate Cox regression analysis. Normalisation of the NLR
following 1 cycle of epirubicin cisplatin and capecitabine (ECX) chemotherapy was
tested for its impact on OS in a subgroup of patients receiving ECX chemotherapy
(n = 14).
Results: 60 patients were included: median age 61 (range: 33-86); 51% men; median
OS 5.9 months (0.7-42.9); 88% had metastasatic disease. On univariate analysis NLR
> 5 (p = 0.009) and mGPS (p = 0.027) correlated with OS, unlike PLR > 300 (p = 0.5).
Multivariate analysis confirmed mGPS (Hazard Ratio (HR); 1.52, 95%CI 1.0-2.3 p =
0.029) and NLR > 5 (HR 2.02 95%CI 1.0-4.1, p = 0.043) as independent predictors of
OS. NLR normalisation post 1 cycle of ECX was associated with improved OS (8.6
months vs 4.6 months, p = 0.014). Results from an independent validation set will be
presented.
Conclusion: Inflammatory indices are independent prognostic predictors in patients
with CUP. Additionally, correction of NLR appears to reflect successful disease
modulating effects of chemotherapy and may be used to predict survival benefit from
treatment. External validation of these scores is ongoing.
Disclosure: All authors have declared no conflicts of interest.
1170P PROGNOSTIC AND PREDICTIVE SIGNIFICANCE OF
PHARMACOGENETIC ANALYSIS IN PATIENTS WITH
CARCINOMAS OF UNKNOWN PRIMARY (CAUP)
C. Papadaki 1 , G. Pentheroudakis 2 , A. Cervantes Ruiperez 3 , E. Lagoudaki 4 ,
D. Petrakis 2 , J. Souglakos 5 , E.R. Braun 6 , V. Georgoulias 7 , D. Mavroudis 5 ,
N. Pavlidis 8
1 Laboratory of Tumor Cell Biology, School of Medicine, University of Crete,
Heraklion, GREECE, 2 Medical Oncology, University General Hospital of Ioannina,
Ioannina, GREECE, 3 Serv. Hematologia y Oncologia Medica, Hospital Clinico
Universitario de Valencia, Valencia, SPAIN, 4 Laboratory of Pathology, School of
Medicine, University of Crete, Heraklion, GREECE, 5 Medical Oncology, University
General Hospital of Heraklion, Crete, GREECE, 6 Hematology and Medical
Oncology, INCLIVA University of Valencia, Valencia, SPAIN, 7 Medical Oncology,
University Hospital of Heraklion, Heraklion, GREECE, 8 Dept. Medical Oncology,
University of Ioannina, Ioannina, GREECE
Purpose: To investigate the prognostic/predictive significance of the expression of
BRCA1, ERCC1, RRM1, TOPO-I, TOPO-IIa, TOPO-IIb, TXR1 TYMS and HIF1a
mRNA in patients with Carcinomas of Unknown Primary (CaUP).
Material and methods: Ninety-three patients with CaUP and available tumoral
samples diagnosed in three institutions were included in the study. The mRNA levels
of the target genes were determined by quantitative real-time PCR from
microdissected cells derived from patients’ tumoral specimens. β-actin and PGK1
were used as reference genes.
Results: Successful amplification of at least one gene was achieved in all samples.
BRCA1, ERCC1, HIF1a and TXR1 were amplified in all samples, while RRM1,
TOPO-I, TOPO-IIa, TOPO-IIb were amplified in 88 samples and TYMS in 86 of
them. Patients’ characteristics were: median age 68 (28-84) years; 53 (57%) males;
ECOG-PS 0 in 23 (25%), 1 in 33 (35%) and ≥ 2 in 37 (40%) patients. The
histological type was: 47 (50%) adenocarcinomas, 18 (19%) squamous cell
carcinomas, 14 (15%) undifferentiated carcinomas, 8 (9%) carcinomas with
neuroendocrine features and 6 (6%) clear cell carcinomas. Forty-one (47%)
patients received a platinum analog as 1 st line treatment, while 21 (24%) were
treated with taxane-based chemotherapy. Patients with high ERCC1 mRNA levels
presented increased median overall survival compared with those with low
ERCC1 expression (mOS: 16.5 versus 8.3 months; p = 0.034). Also, high
compared to low expression of TXR1 or TOPO-I was significantly correlated with
decreased survival (4.5 months vs. 22.6 months; p = 0.015 and 5.9 months vs.
16.5 months; p = 0.042, respectively). A statistical trend for increased survival was
also observed in patients with low HIF1a expression (p = 0.07), while the
expression of the other genes did not show significant prognostic correlation. No
predictive significance of any gene was observed in patients treated with a
platinum analog.
Conclusions: The ERCC1, TXR1, TOPO-IA and HIF1a expression may be used as
prognostic markers in patients with CaUP. The predictive significance of these genes
was not confirmed in the small subgroup of patients treated with platinum analogs.
Disclosure: All authors have declared no conflicts of interest.
1171P THE IMPACT OF PERFORMANCE STATUS AT DIAGNOSIS
ON PROGRESSION-FREE SURVIVAL AFTER SECOND-LINE
CHEMOTHERAPY IN UNFAVORABLE-RISK CANCER OF
UNKNOWN PRIMARY PATIENTS
T. Shimoi, E. Sasaki, M. Kudo, T. Shimoyama, Y. Omuro, R. Okamoto,
Y. Maeda, T. Sasaki
Chemotherapy, Cancer and Infectious Diseases Center Komagome Hospital,
Bunkyo-ku, Tokyo, JAPAN
Introduction: Cancer of unknown primary (CUP) patients classified as an
unfavorable-risk group generally have a poor prognosis. Moreover, there are no
well-defined studies of the efficacy of second-line chemotherapy in unfavorable-risk
CUP patients. Unfavorable-risk CUP patients who had second-line chemotherapy
were retrospectively reviewed, and the characteristics predictive of better
progression-free survival (PFS) after second-line chemotherapy were examined.
Methods: A total of 117 CUP patients was diagnosed in our hospital between May
2002 and April 2012, and 97 patients had more than first-line chemotherapy. A total
of 34 patients (46% of unfavorable-risk patients) received second-line chemotherapy.
Results: Among 34 patients, there were 21 female patients (62%). The median age
was 60 (range, 39–74) years. The majority of patients had PS 1 (75%).
Volume 23 | Supplement 9 | September 2012 doi:10.1093/annonc/mds405 | ix381