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612P ARE PATIENTS WITH RESECTABLE RECTAL CANCER
BETTER OFF IN THE ERA OF MULTIDISCIPLINARY CARE?
V.T. Broadbridge, J. Hardingham, K. Pittman, A. Townsend, M. Colbeck,
B. Hooper, T. Price
Department of Medical Oncology, The Queen Elizabeth Hospital, Woodville
South, SA, AUSTRALIA
Introduction: The management of rectal cancer (RC) has evolved with the
introduction of Total Mesorectal Excision Surgery (TME), use of Magnetic
Resonance Imaging (MRI) for staging, changes in chemotherapy and radiotherapy
and multidisciplinary meetings (MDTs). The timing of therapy for T3/4 and/or node
positive RC has also changed with neoadjuvant chemoradiotherapy (CRT) becoming
standard based on lower local recurrence rates. Given these changes in management
over time, we assessed disease free survival (DFS), overall survival (OS) and rates of
local and distant recurrences of patients treated at The Queen Elizabeth Hospital
(TQEH) between 1992 to 2006.
Method: Demographic and outcome data of patients diagnosed with early stage RC
from TQEH Cancer Registry from 2 different time cohorts 1992-99 (A) and 2000-06
(B) were analysed. Survival analysis was by Kaplan-Meier method and prognostic
factors were analysed using cox proportional hazards regression.
Results: 423 patients were identified; 235 in A, 188 in B. Patient characteristics
were generally similar. Median age A 68.1 yrs (range 32-94), B was 67.4 yrs
(range 25-92). More patients had stage B in cohort A (47%) v B (39%). 56% of
patients had surgery alone in cohort A compared to 47% in cohort B. Rates of
any “adjuvant” therapy was similar (A = 41% v B = 46%), although there was a
doubling in proportion of patients who received neoadjuvant CRT in the latter
cohort (A= 7.2% v B= 16%). There was a significant improvement in rate of 5
year local/distal recurrence; A 87%/71% v B 95%/81%, p < 0.0001. 5 year DFS
improved over time; A 65.2% v B 73.3%, p = 0. 03. 5 year OS was A 66.1% v B =
78.4% and median OS for A was 14.62 years and not reached for cohort B (p =
0.007). Stage and cohort B were prognostic for OS while age, sex, preoperative RT
and any chemotherapy were not.
Conclusion: There has been significant improvement in DFS, OS and local and
distant recurrence rates in patients diagnosed with early stage RC. The trend to
greater use of neoadjuvant CRT in the latter cohort is consistent with changes in
practice, and this may be a factor in improved local control, but does not appear to
impact on survival. Other factors likely to have improved overall outcomes include:
increased TME rates, improved preoperative staging including use of MRI and
potentially the introduction of MDTs.
Disclosure: All authors have declared no conflicts of interest.
613P PPPP1R13L VARIANT ASSOCIATED WITH PROGNOSIS FOR
PATIENTS WITH RECTAL CANCER
J.G. Kim, B.W. Kang, S.J. Lee, Y.J. Lee, Y.S. Chae
Oncology/Hematology, Kyungpook National University Medical Center, Daegu,
KOREA
Backgroud: Genetic variants related to apoptosis and DNA repair pathways may
play a meaningful role in cancer progression as well as carcinogenesis. Among
them, ERCC1 and PPP1R13L polymorphisms was shown to synergistically affect
these pathways. The aim of this study was to investigate the association between
these genetic variants and prognosis of colorectal cancer (CRC) operated
curatively.
Methods: A total of 349 CRC patients underwent curative surgery were
consecutively enrolled between March 2003 and August 2006. DNA was
extracted from fresh frozen normal tissue and each polymorphism (ERCC1
rs11615 and rs735482; PPP1R13L rs1005165 and rs967591) was genotyped by
polymerase chain reaction-restriction fragment length polymorphism
(PCR-RFLP).
Results: No statistical significance between these 4 variants and survival in a
multivariate analysis for all CRC patients. However, the CC genotype of the
PPP1R13L rs1005165 was significantly associated with worse survival in 164
patients with rectal cancer (HR = 2.10 and P = 0.037 for RFS; HR = 2.27 and P =
0.039 for DSS, respectively) as a recessive model of the C allele in a multivariate
analysis. Meanwhile, no statistical differences in clinicopathologic characteristics
were observed according to the PPPIR13L rs1005165 genotype in patients with
rectal cancer.
Conclusions: Our results suggest that PPP1R13L rs1005165 variant is possible
prognostic marker for patients with rectal cancer.
Disclosure: All authors have declared no conflicts of interest.
Annals of Oncology
614P NEOADJUVANT TREATMENT IN RECTAL CANCER: LONG- VS
SHORT-COURSE RADIOTHERAPY
J. Casalta-Lopes1 , I. Nobre-Góis1 , T. Teixeira1 , M. Borrego1 , P. Soares1 ,A.Sá2 1 2
Radiation Oncology, CHUC, Coimbra, PORTUGAL, Medical Oncology, CHUC,
Coimbra, PORTUGAL
Introduction: Two schemes for pre-operative radiotherapy (RT) in locally advanced
rectal carcinoma (RC) are possible: long-course irradiation (45 – 50.4 Gy / 25 – 28
fr) with chemotherapy (CHT), followed by surgery after 6 to 8 weeks; and
short-course irradiation (25 Gy / 5 fr), followed by surgery usually 1 week after.
Some studies have shown a downstaging effect with delayed surgery in short-course
irradiation Goal: Compare results of different irradiation schemes for neoadjuvant
treatment of RC in a Radiation Oncology Department.
Methods: Patients with RC treated pre-operatively between 2002 and 2012 were
included. RT was performed according to 2 schemes: long-course scheme (GROUP
1) using only RT (GROUP 1A), with oral CHT (GROUP 1B) or infusion CHT
(GROUP 1C); and short-course scheme (GROUP 2).
Results: 265 patients were included, 227 in GROUP 1. GROUP 1A were older than
GROUP 1B and 1C (p < 0.001). Grade 3 and 4 toxicity was only observed in the
groups treated with concomitant CHT. Median time to surgery was 7 weeks.
Response to treatment was statistically different regarding node downstaging (58.3%
vs 77.1% vs 55.8%; p = 0.015) and locoregional response (56.3 vs 82.6% vs 70.5%;
p = 0.020). GROUP 2 patients were older than those from GROUP 1 (p < 0.001), had
lower Karnofsky index (p = 0.004) and several comorbidities. 15.8% patients (vs 0%)
were considered M1 and more tumours were further than 5 cm from the anal margin
in GROUP 2 (68.4% vs 49.8%; p = 0.033). No acute toxicity was observed in GROUP
2 and median time to surgery was 2 weeks, with 65.7% of locoregional response.
Considering time to surgery (≤1 week vs >1 week) there were significant differences
in locoregional response (28.6% vs 75.0%, p = 0.033), with 2 complete responses in
those with greater time to surgery.
Conclusions: These results are according to literature: long-course scheme with
concomitant CHT provided better locoregional response, although with some acute
toxicity; a higher time to surgery in short-course scheme appears to have better
results, with no increase in surgical complications. Short-course irradiation with
surgery delay appears to be a useful alternative to long-course radiochemotherapy,
namely in patients with advanced age and associated comorbidities.
Disclosure: All authors have declared no conflicts of interest.
1704P PROSPECTIVE FEASIBLE STUDY TO EVALUATE
NEOADJUVANT-SYNCHRONUS S-1 + RT FOR LOCALLY
ADVANCED RECTAL CANCER: A MULTICENTER PHASE-II
TRIAL (UMIN ID03396)
M. Inomata
Department of Gastroenterological Surgery, Oita University Faculty of Medicine,
Oita, JAPAN
Background: Fluorouracil-based chemoradiotherapy (CRT) is regarded as a standard
perioperative treatment in locally advanced rectal cancer. We investigated the efficacy
and safety of substituting fluorouracil with the oral prodrug TS-1.
Methods: A multi-institutional (17 specialized centers), interventional phase II trial,
was conducted from April 2009 to August 2011.This study is registered with
UMIN-CTR, number C003396. For inclusion, patients must fulfill the following
requirements before neoadjuvant CRT: (i) histologically proven rectal carcinoma; (ii)
tumor located in the rectum (upper,lower); (iii) cancer classified as T3-4, N0–3 and
M0; Two cycles of neoadjuvant CRT with TS-1 (100 mg/m 2 on days 1-5, 8-12, 22-26,
and 29-33) is administered, and irradiation (total 45Gy/25fr, 1.8Gy/day, on days 1-5,
8-12, 15-19, 22-26, and 29-33) is performed. Total mesorectal excision with D3
lymphadenectomy is performed during the 4th and 8th week after the end of the
neoadjuvant CRT. The primary end-point is rate of complete treatment of
neoadjuvant CRT. Secondary endpoints are response rate of neoadjuvant CRT,
short-term clinical outcomes, rate of curative resection, and pathological response
(grade2/3).
Results: This trial included 37 patients. A complete treatment of neoadjuvant CRT
was found in 83.3% of patients (95%CI;71.2 ∼ 95.5%), and an adverse event (grade 3/
4) occurred in 4 patients(11.1%). A rate of an overall downstaging (PR/CR;RECIST
1.0) was 83.3% (95%CI; 71.2 ∼ 95.5%), and a pathologic response rate was 50.0%
(95%CI; 33.7 ∼ 66.3%).
Conclusion: Our prospective phase-II study demonstrated that a
neoadjuvant-synchronus TS-1 + RT for locally advanced rectal cancer was feasible in
terms of pathological response and adverse events.
Disclosure: All authors have declared no conflicts of interest.
ix208 | Abstracts Volume 23 | Supplement 9 | September 2012