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Annals of Oncology
was stipulated at 8 weeks after chemoradiation (CRT) with primary end point
histological circumferential resection margin (CRM) negative rate.
Results: From Apr 2009-Oct 2011 82 pts were recruited. At baseline: male/female 61/
21, median age 62, WHO PS 0/1/missing 60/19/3. On MRI tumour was T2/3/4 in 6/
67/9 and N0/1/2 in 14/41/27 pts, mesorectal fascia or levator-sphincter complex was
threatened (≤ 1mm gap) in 45 (55%), definitely involved in 21 (26%) and breached
in 16 pts (20%). 2 pts did not commence RT and were withdrawn from trial
treatment. The no. (%) of significant acute toxicities were diarrhoea grade (Gr)3 20
(25%), acneiform rash Gr3 7 (9%), fatigue Gr3 6 (8%), thrombotic event Gr3 1 (1%)
and Gr4 5 (6%) and febrile neutropenia Gr3 1 (1%) and Gr4 1 (1%). 75 pts had
surgery (36 anterior resection, 37 abdominoperineal, 2 Hartmans). Post-resection
histology showed a negative CRM (>1mm) in 67 (89%), a pathological complete
response (pCR) (T0N0) in 14 (19%), T0/1/2/3/4 in 15/2/16/40/2 and N0/1/2 in 51/
15/9 pts. 38 of the 75 resected pts (51%) had their T and 49 of 63 (78%) their N1-2
stage downstaged. 5 pts with a clinical CR (cCR) post CRT did not have surgery and
were alive with no evidence of disease at 8, 12, 14, 24 and 26 m.
Conclusion: EXCITE is the largest reported phase II trial of a triplet CRT regime
including EGFR targeted therapy in LARC, showing acceptable toxicity and
compliance. In MRI-defined locally advanced/borderline unresectable disease a
combined pCR + cCR rate of 19/80 (24%) is promising. Data on KRAS and BRAF
influence will be available by Aug 2012.
Disclosure: S. Gollins: Research funding grants from Merck and Pfizer Honoraria
from Roche (Advisory Boards). All other authors have declared no conflicts of
interest.
609P FIRST RESULTS FROM THE PHASE I DUAL RECTAL
ANGIOGENESIS MEK INHIBITION RADIOTHERAPY
(DREAMTHERAPY) TRIAL IN LOCALLY ADVANCED RECTAL
CANCER
F.E. Marti Marti 1 ,A.Backen 2 , A.G. Renehan 3 , A. Jackson 4 , P. Manoharan 5 ,
O. Ataman 6 , V. Misra 7 , G.C. Jayson 1 , C. Dive 2 , M.P. Saunders 7
1 Medical Oncology, The Christie NHS Foundation Trust, Manchester, UNITED
KINGDOM, 2 Clinical and Experimental Pharmacology, The Paterson Institue for
Cancer Research, Manchester, UNITED KINGDOM, 3 Surgery, The Christie
Hospital NHS Foundation Trust and Paterson Institute for Cancer Research,
Manchester, UNITED KINGDOM, 4 Radiology, Wolfson Molecular Imaging Centre,
Manchester, UNITED KINGDOM, 5 Radiology, The Christie Hospital NHS
Foundation Trust, Manchester, UNITED KINGDOM, 6 Rockit, Astra Zeneca,
Alderley Park, UNITED KINGDOM, 7 Clinical Oncology, The Christie Hospital NHS
Foundation Trust, Manchester, UNITED KINGDOM
Background: Less than 15% of patients (pts) receiving pre-operative chemoradiation
(CRT) for rectal cancer have a complete pathological response (pCR). We tested the
hypothesis that the addition of cediranib (a VEGFR TKI) or selumetinib (a MEK
inhibitor), in combination with CRT, increases the proportion of complete
responders. A translational protocol was also developed to study potential predictive
biomarkers.
Methods: This hypothesis was evaluated in a dual phase I design. The drugs are
evaluated in parallel in an intertwined design: once a cohort of pts on cediranib
completed treatment and during the toxicity assessment period, another cohort of
pts was commenced on selumetinib at the next dose level. Alternating cohorts
maximised the efficacy of their evaluation. The analysis here is for cediranib only. Pts
received CRT (45Gy in 25#, capecitabine 825 mg/m 2 twice daily for 35 days) in three
cohorts with cediranib: 15 mg, 20 mg and 30 mg/once daily (OD). Dose escalation
was done upon fulfilment of the safety criteria outlined in the protocol. Cediranib
was commenced 10 days prior to the start of CRT and continued throughout. Pts
were followed up until and then after surgery. Safety, RECIST and pathological data
were collected. In addition, blood, tissue and DCE-MRIs were obtained at baseline,
post-monotherapy, throughout and post CRT for the study of candidate biomarkers.
Results: 15 mg cohort: 3 pts were recruited. 2 pts had a pCR and the 3rd pt had a
clinical complete response (cCR) not requiring surgery. 20 mg cohort: 3 pts were
treated. 1 had a cCR and ypT3N0 on resection. The other 2 had partial responses on
MRI with ypT3N0 and ypT3N2 pathologically. 30 mg cohort: 3 pts were recruited at
this dose level. Two pts had a cCR and the other one is waiting restaging. There was
one DLT in this cohort (Grade III lethargy). This cohort will be expanded to a
maximum n = 6. As yet, all pts have had R0 resections and completed all planned
treatment (except pt with DLT who did not complete capecitabine). cCR pts remain
disease free and have not had surgery.
Conclusions: The addition of cediranib to pre-operative CRT is a well tolerated
regimen. All pts have responded with 5 out of 8 evaluable pts (62.5%) having either a
pCR (n = 2) or cCR (n = 3). Updated clinical data, proposed optimal dose and
translational data will be available for presentation at the meeting.
Disclosure: F.E. Marti Marti: Dr Marti’s research fellowship is funded in equal parts
by Cancer Research UK and Astra Zeneca. O. Ataman: Dr Ataman is an
Astra Zeneca employee. G.C. Jayson: AZ advisory boards and research funding. M.
P. Saunders: I have previously been a paid advisor on an AZ trial with
AZD2171 (Horizon II). However, I have no conflicts on the use of this agent
in the DREAMtherapy trial. All other authors have declared no conflicts
of interest.
610P UTILITY OF MAGNETIC RESONANCE IMAGING FOLLOWING
LONG-COURSE PRE-OPERATIVE CHEMO-RADIOTHERAPY
FOR LOCALLY ADVANCED RECTAL CANCER
D.J. Lucey 1 , A. Murphy 2 , V. Curran 3 , M. McCourt 4 , E. Andrews 4 ,M.O’Riordain 3 ,
D.G. Power 5 ,S.O’Reilly 5 , P.J. Kelly 4
1 Radiotherapy Department, Cork University Hospital, Cork, IRELAND, 2 Medical
Oncology Department, Cork University Hospital, Cork, IRELAND, 3 Surgery,
Mercy University Hospital, Cork, IRELAND, 4 Surgery, Cork University Hospital,
Cork, IRELAND, 5 Medical Oncology, Cork University Hospital, Cork, IRELAND
Aims/Rationale: Neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal
cancer is associated with improved local control and results in tumour down-staging.
The purpose of this study was to assess whether MRI performed following
chemoradiotherapy alters surgical management.
Methods: All patients with locally advanced (cT3-4 or cN+ by endorectal ultrasound,
computed tomography, or magnetic resonance imaging) rectal adenocarcinoma
diagnosed in 2010 and 2011 at Cork University Hospital/Mercy University Hospital
and treated with long course preoperative CRT followed by radical resection were
identified and their records were retrospectively reviewed from prospectively
maintained institutional databases . Only patients who had MRI pre- and
post-neoadjuvant therapy were eligible for inclusion.
Results: Thirty patients had MRI pre- and post long course chemoradiotherapy.
Male: Female was 3:2, the median age was 60 (range 36-77). Abdominoperineal
resection was performed in 12 of these patients, and anterior resection in 18 patients.
The median radiation dose was 50.4 Gy with concurrent 5FU-based chemotherapy.
Median time from completion of CRT to post-treatment MRI was 30 days, and the
median time to surgery from the 2 nd MRI was 23 days. Only 1 of the 30 patients
(3.3%) showed disease progression on the repeat scan and R0 resection was achieved
in this case. Three patients (10%) achieved pathologic complete remission and none
of these had a radiographic CR on post-treatment MRI. Two patients (6.6%) had
positive circumferential resection margins and neither was predicted by
post-treatment MRI.
Conclusions: MRI following neoadjuvant therapy prior to surgical resection did not
alter clinical management in this small retrospective series. The utility of post CRT
MRI prior to definitive resection is unclear and international guidelines do not
recommend this approach.
Disclosure: All authors have declared no conflicts of interest.
611P EFFECTS OF RADIOTHERAPY (RT) AND
CHEMORADIOTHERAPY (CRT) ON LYMPH NODES (LNS) IN
PATIENTS WITH RECTAL CANCER: EVALUATION OF
NUMBERS OF RETRIEVED LNS AND LN SIZE
K. Okada1 , S. Sadahiro2 , T. Suzuki1 , A. Tanaka1 , A. Kamijo1 1
Gastrointestinal Surgery, Tokai University School of Medicine, Isehara, JAPAN,
2
Gastrointestinal Surgery, Tokai University School of Medicine Isehara Campus,
Isehara, JAPAN
Background: In patients with colorectal cancer, retrieval of 12 or more LNs has been
reported to be associated with better outcomes. Preoperative RT or CRT reduces the
number of retrieved LNs. The effects of RT and CRT on LNs may be different
between LNs inside and LNs outside the radiation field.
Methods: The study group comprised 368 patients with a cStage II/Stage III
adenocarcinoma of the rectum between 1991 and 2010. 108 received surgery alone
(S group), 158 received preoperative RT with 20 Gy in 10 frs. plus IORT with 15 Gy
(RT20 group), and 102 received preoperative RT 40 or 45 Gy in 20 or 25 frs. plus
concurrent chemotherapy with oral UFT or S-1 (RT45 group). The sizes of LNs
(shortest axis, longest axis, and area) were measured on specimens stained with
hematoxylin and eosin, using a computer digitizer. LNs were divided into 2 groups
according to their distribution, inside the radiation field and outside.
Results: The total number of retrieved LNs was 1718 in the S group, 2337 in the
RT20 group, and 917 in the RT45 group. The total number of retrieved LNs was
significantly lower in the RT45 group (9.0 ± 6.9) than in the S group (15.8 ± 10.6)
and the RT20 group (14.8 ± 9.1). (p < 0.001, p < 0.001) The numbers of retrieved LNs
within the radiation field were significantly lower in the RT20 group (4.6 ± 4.0) and
the RT45 group (4.1 ± 4.0) than in the S group (6.4 ± 5.8). (p < 0.008,p < 0.001) The
numbers of retrieved LNs outside the radiation field did not differ significantly
among the groups. As compared with the S group (4.9 ± 3.1mm), LNs inside the
radiation field were significantly smaller in the RT20 (4.4 ± 2.5mm) group and the
RT45 group (4.1 ± 2.7mm). LNs outside the radiation field were also significantly
smaller in the RT20 group and the RT45 group than in the S group although the
numbers of LNS did not differ significantly. These findings were most likely caused
by the effects of concurrent chemotherapy.
Conclusions: Our results showed that the response of LNs to RT/CRT differed
between inside and outside of the radiation field. The numbers of retrieved LNs
should be separately assessed inside and outside the radiation field to ensure accurate
disease staging.
Disclosure: All authors have declared no conflicts of interest.
Volume 23 | Supplement 9 | September 2012 doi:10.1093/annonc/mds397 | ix207