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Annals of Oncology
practical for examining a patient’s KRAS codon61, codon146, BRAF, NRAS, and
PIK3CA gene status.
Disclosure: All authors have declared no conflicts of interest.
575P BIOPSY SPECIMENS OBTAINED 7 DAYS AFTER STARTING
CHEMORADIOTHERAPY (CRT) PROVIDES RELIABLE
PREDICTORS OF RESPONSE TO CRT FOR RECTAL CANCER
T. Suzuki 1 , S. Sadahiro 1 , A. Tanaka 1 , K. Okada 1 , A. Kamijo 1 , S. Kawada 2
1 Gastrointestinal Surgery, Tokai University School of Medicine, Isehara, JAPAN,
2 Radiology, Tokai University School of Medicine, Isehara, JAPAN
Background: Preoperative CRT is a standard treatment for locally advanced
rectal cancer (LARC). The histologic response to CRT or the downstaging has
been reported to be closely related to oncologic outcomes. Various biomarkers
in biopsy specimens obtained before CRT have been investigated as
predictors of response, however, reliable predictive biomarkers remain to be
established.
Methods: The study group comprised 101 consecutive patients with LARC who
received preoperative CRT of 45Gy with oral uracil/tegafur (UFT) or S-1. We
evaluated histologic findings on H-E staining and immunohistochemical expressions
of Ki67, p53, p21, and apoptosis in biopsy specimens obtained before CRT and 7
days after starting CRT. These findings were contrasted with the rate of histologic
marked regression and the degree of tumor shrinkage.
Results: In biopsy specimens obtained before CRT, the degree of tumor shrinkage
on barium enema (BE) were significantly greater in patients with p21-positive
tumors (52 ± 11%) than in those with p21-negative tumors (45 ± 16%) (p < 0.01).
In biopsy specimens obtained 7 days after starting CRT, the histologic marked
regression according to the tumor regression grade (TRG) criteria was significantly
higher in apoptosis-positive patients (57.1%) and p21-positive patients (49.2%)
than in apoptosis-negative patients (30.1%) and p21-negative patients (20.0%) (p =
0.02 and p < 0.01, respectively). The degrees of tumor shrinkage based on BE and
on MRI were both significantly higher in apoptosis-positive patients (55 ± 12%, 81
± 15%) and p21-positive patients (52 ± 13%, 74 ± 19%) than in apoptosis-negative
patients (45 ± 15%, 68 ± 19%) and p21-negative patients (41 ± 13%, 66 ± 19%) (p <
0.01, p < 0.01, p < 0.01 and p = 0.04, respectively). Histologic changes in H-E
stained biopsy specimens significantly correlated with marked regression as well as
with tumor shrinkage based on BE and MRI (p < 0.01, p < 0.01 and p = 0.03,
respectively).
Conclusions: Immunohistochemical expressions of p21 and apoptosis together with
histologic changes on H-E-stained biopsy specimens obtained 7 days after starting
CRT are strong predictors of response to CRT.
Disclosure: All authors have declared no conflicts of interest.
576P ADVERSE EVENTS IN ELDERLY PATIENTS ON ADJUVANT
THERAPY WITH UFT/LV OR S-1 FOR STAGE III COLON
CANCER: ACTS-CC TRIAL [TRICC0706]
M. Ishiguro 1 , H. Uetake 1 , T. Ishikawa 1 , Y. Kusunoki 2 , F. Kinoshita 2 ,
N. Kashiwagi 2 , Y. Nagata 2 , Y. Matsubara 2 , K. Sugihara 3
1 Department of Translational Oncology, Tokyo Medical and Dental University,
Graduate School, Tokyo, JAPAN, 2 Translational Research Informatics Center,
Foundation for Biomedical Research and Innovation, Kobe, JAPAN, 3 Department
of Surgical Oncology, Tokyo Medical and Dental University, Graduate School,
Tokyo, JAPAN
Background: The ACTS-CC trial is a phase III trial designed to validate
non-inferiority of S-1 to UFT/ LV, a standard adjuvant therapy for stage III colon
cancer in Japan. We reported the safety profile of this trial (Brit J Cancer 2012). To
clarify the characteristics of adverse events (AEs) in elderly patients, subgroup
analysis was performed.
Methods: 20-80 aged patients with stage III colon cancer were randomly assigned to
receive UFT/LV (UFT: 300 to 600 mg/day and, LV: 75 mg/day on days 1-28, followed
by 7 days rest, 5 courses) or S-1 (80 to 120 mg/day on days 1-28, followed by 14 days
rest, 4 courses). We compared treatment status and safety among group A (age ≤ 70),
group B (age 71-75) and group C (age 76-80).
Results: A total of 1,504 patients (756 in S-1 group, 748 in UFT/LV group,) were
analyzed. The numbers of patients of group A, B and C were 506 (69%), 160
(20%) and 90 (11%), and the rates of patients with PS 1 in each group were
2.6%, 4.3% and 16.8%, respectively. Pre-treatment value of Hemoglobin of group
B and C was lower than that of group A, while there were no differences in that
of neutrophils, platelets and creatinine. In S-1 treatment, incidences (any grades)
of anemia (group A: 29%, B: 37%, C: 47%), anorexia (30%, 34%, 46%) and
fatigue (25%, 29%, 39%) were higher in group C. In ≥ grade 3 AEs, incidences of
anorexia (3%, 7%, 13%), diarrhea (4%, 3%, 7%) and fatigue (2%, 3%, 7%) were
higher in group C. In UFT/LV treatment, incidence (any grades) of anorexia
(22%, 33%, 30%) and anemia (24%, 32%, 35%) were higher in group B and C,
while incidence of elevation of AST (23%, 15%, 12%) and ALT (25%, 15%, 12%)
were higher in group A. The completion rates of S-1 treatment was lower in
group C (group A: 78%, B: 77%, C: 69%), although those of UFT/LV did not
differ among the groups. There was no difference in the rate of discontinuation
due to AEs listed on the discontinuation criteria among the groups, while that
due to AEs not listed on the criteria (i.e. physician’s judgment or patient’s
request) was higher in group C.
Conclusions: In elderly patients, subjective AEs such as anorexia and fatigue were
common, and mild anemia was observed in one-third of ≥71 aged patients.
Disclosure: All authors have declared no conflicts of interest.
577P EXTENSIVE LIVER RESECTIONS AND PREOPERATIVE
REGIONAL INTRAARTERIAL CHEMOTHERAPY IN PATIENTS
WITH LIVER COLORECTAL CANCER METASTASES AND
UNFAVOURABLE PROGNOSTIC FACTORS
S. Khays 1 , K. Mamontov 1 , A. Kotelnikov 2 , S. Lazarev 1 , A. Lazarev 3
1 Liver and Pancreas Surgery, Altai Branch of N. N. Blokhin Russian Cancer
Research Centre, Barnaul, RUSSIAN FEDERATION, 2 Liver and Pancreas
Surgery, N. N. Blokhin Russian Cancer Research Centre, Moscow, RUSSIAN
FEDERATION, 3 N. N. Blokhin Russian Cancer Research Centre, Altai Branch of
N. N. Blokhin Russian Cancer Research Centre, Barnaul, RUSSIAN
FEDERATION
Objective: To analyze patients with negative prognostic factors, as well as overall and
disease-free survival.
Materials and methods: 101 patients with liver colorectal cancer metastases were
enrolled in this local observational study. All patients undergone preoperative
regional intraarterial chemo- or biotherapy (group 1 - FOLFOX 6, group 2 -
FOLFOX 6 + bevacizumab) followed by liver resection. Synchronous metastases – in
54 patients (53%). Metachronous metastases – in 47 (47%). Bilobate lesion – in 62
patients (62%). Solitary metastasis – in 46 (46%). Multiple metastasis – in 55 (54%).
Partial regression of tumor was observed in 26 patients (26%), stabilization – in 53
(53%). Progression – in 21 (21%). Extensive liver resection with resection of
contralateral lobe was performed in 39 patients (39%). Standard hepatectomy – in 71
(70%). Extended hepatectomy – in 30 (30%). Extrahepatic metastases – in 23 patients
(23%). Metastases in lymph nodes of hepatoduodenal ligament – 18 (18%).
Results: Univariate analysis revealed three unfavorable factors: bilobate lesion of the
liver (p = 0.04), multiple liver metastases (p= 0.00029), metastases to the
hepatoduodenal ligament (p = 0.001). Multivariate analysis revealed two unfavorable
prognostic factors: multiple liver metastases (p = 0.015), metastases to the
hepatoduodenal ligament (p = 0.04). Overall survival with FOLFOX 6 + bevacizumab:
Median – 33 months, 3-years - 36 ± 10, 5 years - 12 ± 7. With FOLFOX 6: Median –
29 months, 3 years – 42 ± 7, 5 years – 14 ± 6. Overall survival in case of metastases to
the lymph nodes of hepatoduodenal ligament. With metastases: Median – 27
months, 3 years – no, 5 years – no. Without metastases: Median – 35 months, 3
years - 49 ± 7, 5 years – 16 ± 6. Overall survival depending on the number of liver
foci. Solitary foci: Median – 35 months, 3 years - 42 ± 10, 5 years – 23 ± 10. Multiple
foci: Median – 28 months, 3 years – 51 ± 10, 5 years – 12 ± 7.
Conclusion: The main criteria characterizing tumor aggressiveness are the number of
liver foci and metastases to the hepatoduodenal ligament, which determine tumor
spreading.
Disclosure: All authors have declared no conflicts of interest.
578P COMPARISON OF PATHOLOGICAL RESPONSES (PR)
OBSERVED ON COLORECTAL CANCER METASTASES (CRCM)
RESECTED AFTER DIFFERENT PREOPERATIVE
TREATMENTS
M. van den Eynde 1 , M. Gizzi 2 , G. Pairet 3 , P. Lefesvre 4 , V. Lannoy 5 , J. Gigot 6 ,
B. Navez 6 , J. Canon 2 , C. Sempoux 3 , J. Carrasco 2
1 Medical Oncology, Cliniques Universitaires St-Luc, Brussels, BELGIUM,
2 Medical Oncology, Grand Hopital de Charleroi, Charleroi, BELGIUM,
3 Pathology, Cliniques Universitaires St-Luc, Brussels, BELGIUM, 4 Pathology, IPG
Loverval, Loverval, BELGIUM, 5 Centre du Cancer, Cliniques Universitaires
St-Luc, Brussels, BELGIUM, 6 Surgery, Cliniques Universitaires St-Luc, Brussels,
BELGIUM
Background: Irinotecan (IR) or oxaliplatin (OX)-based regimens optionally
combined with anti-VEGF or anti-EGFR Target Therapies (TT) are used as
preoperative treatment for metastatic colorectal patients before resection of CRCM.
Best combination remains unclear. The study purpose was to compare PR observed
on resected CRCM after different preoperative treatments.
Methods: 114 patients engaged for CRCM resection after 2005 were included in this
retrospective analysis. PR was evaluated on 296 resected CRCM according to the
pathological Tumor Regression Grading scale (TRG), grading PR from complete
(TRG1) to absent (TRG5). Mean TRG of resected metastasis was compared based on
Kruskall-Wallis and Mann-Whitney tests. Cumulative PFS were calculated by
Kaplan-Meir method and compared by log-rank test.
Volume 23 | Supplement 9 | September 2012 doi:10.1093/annonc/mds397 | ix197