Adams, R

Bell, S

Berkman, L

Gilbert, D

Glynne-Joones, R

Goh, V

Gregory, W

Harrison, M

Hawkins, Maria

Hutchins, G

Kachnic, L

Lee, M

McParland, L

Muirhead, R

O'Neil, B

Rao, S

Renehan, A

Sebag-Montefiore, D

Smith, A

Velikova, G

Radiotherapy and Oncology

English

D. Sebag-Montefiore

R. Adams

S. Bell

L. Berkman

D. Gilbert

R. Glynne-Joones

V. Goh

W. Gregory

M. Harrison

L. Kachnic

M. Lee

L. McParland

R. Muirhead

B. O'Neil

G. Hutchins

S. Rao

A. Renehan

A. Smith

G. Velikova

M. Hawkins

Crossref

EP-1277: Optimising RT dose for anal cancer - the development of three clinical trials in one platform

ORA - Oxford University Research Archive

Optimising RT dose for anal cancer - the development of three clinical trials in one platform

Oxford University Research Archive

S685                                                                                     ESTRO 36  _______________________________________________________________________________________________   Results  Dose escalation radiotherapy treatment reports a benefit in pCR (9.5 % vs 20 %   p= 0.029), tumoral downstaging rate (42.7 % vs 60%   p=0.020), nodal downstaging rate (62.9% vs 7.7%   p= 0.173) and ypT0 rate (10.3% vs 20 p= 0.049). Complete microscopical resection increses on integrated boost group (93.4% vs 98% statistically non-significant). In the comparison between both groups by Contingency Table , no statistically significant differences were found on toxicity (G2 27.5% vs 37%; G3 3.1 % vs 9%) or surgical complications (35.7% vs 40%). With a follow up of 181 months, the study reports a statistically significance on disease free survival (56.1% vs 76.7 % p= 0.036 Kaplan-Meier Test), and overall survival (21% vs 46.65 p=0.02) in the SIB group. Locorregional recurrence-free survival also improves but without statistical significance (88% vs 94.9 %  Kaplan-Meir method). Tumoral downstaging was considered as an independent factor on DFS (HR 1.914  p=0.004  Cox model.)  Conclusion  Escalation dose radiotherapy group achieved statistical differences in pCR (ypT0 yN0), tumoral downstaging rate, overall survival (OS) and distant disease free survival (DFS). pCR could be considered as a prognostic factor on OS. The variable tumoral downstaging demonstrate a great value as an independent factor on DFS.    EP-1275  Patients with locally advanced rectal cancer (larc): predictive factors of pathological response S. Montrone1, A. Sainato1, R. Morganti2, C. Vivaldi3, B. Manfredi1, C. Laliscia1, M. Cantarella1, G. Coraggio1, G. Musettini3, A. Gonnelli1, G. Masi3, P. Buccianti4, F. Pasqualetti1, F. Paiar1 1OSPEDALE SANTA CHIARA, Radiotherapy, PISA, Italy 2OSPEDALE SANTA CHIARA, Oncology- Biostatistical Consulting, PISA, Italy 3OSPEDALE SANTA CHIARA, Oncology, PISA, Italy 4OSPEDALE CISANELLO, Colon-rectal Surgery, PISA, Italy  Purpose or Objective  Preoperative RTCT followed by total mesorectal excision (TME) is the standard of cure in patients (pts) with LARC. After neoadjuvant RTCT the rate of complete pathologic response (pCR) range between 15%-30% and many studies are trying to find predictive factors of response in order to select pts who could benefit from organ-preserving options (local excision or “wait and see approach”). This study aim to identify predictive factors of T and N response of neoadjuvant RTCT.  Material and Methods  We analyzed retrospectively the data of 119 pts affected by LARC (all of them cT3-T4 and 90,7% cN+) treated by neoadjuvant RTCT (50.4 Gy in 28 FF + capecitabine 1650 mg/mq/day)  followed by TME surgery, between January 2008 and April 2014, in Pisa Universitary Hospital. Based on MR-images, we analyzed T characteristics (clinical stage, site respect to anal verge, cranio-caudal extension, number of  involved quadrants, volume, distance from mesorectal fascia) and N characteristics (clinical stage, number of nodes with short axis  ≥ 5mm and distance from mesorectal fascia), at diagnosis and at restaging (before surgery) and their variations, in order to find a correlation with pathological T and N stage. Results   All pts completed planned RTCT. The overall pCR rate was 25,2%. In the multivariate analysis (T parameters) only the number of involved quadrants (p=0,002) and the cranio-caudal extension at diagnosis (p=0,043) resulted to be predictive of pCR.  At the pathological findings, the rate of pN+ was 21% compared to 90,7% of the clinical stage. In the multivariate analysis (N parameters) only the number of nodes (short axis ≥ 5mm) at diagnosis was shown to be predictive of pN0, both as a continuous variable (p=0,004) that as dichotomous variable (p<0,0001) with a threshold value of 3 nodes. T and N variations, at pre-surgical restaging, were not significantly correlated to pathological outcomes. Conclusion  To know predictive factors of pCR and pN0 after neoadjuvant RTCT could influence the surgical approach. T size and T distance from the anal verge seem to be two well established predictive factors of response . Based on our retrospective analysis, we can add that the number of involved quadrants and the number of nodes (≥5mm) at diagnosis could be additional predictive parameters.  EP-1276  Clinic and radiobiology of hypofractionated radiotherapy for metastatic liver tumors. Pilot results. T. Latusek1, L. Miszczyk1, J. Rembak-Szynkiewicz2 1Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Radiotherapy, Gliwice, Poland 2Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Radiology, Gliwice, Poland  Purpose or Objective  Liver metastases are the most common tumor in this organ and majority of them are metastases of adenocarcinomas of the gastrointestnal tract. Radiotherapy is often used as alternative method to surgery. Due to promising results of the extracranial stereotactic radiotherapy used to treat primary metastatic tumors of the lung it is applied also for primary or metastatic liver lessions. The aim was to evaluate the efficacy of hypofractionated radiotherapy for metastatic liver tumors. Material and Methods  Clinical material consists of 28 liver malignant liver lesions treated with stereotactic hypofractonated radiotherapy at the Cancer Center, MSC Memorial Institute in Gliwice. Tumor size and volume reflecting initial numer of cancer cells were estimated Patient’s age was in the range of 33-84 years (median 64).  All liver metastases  were irradiated with a total dose of 45 Gy given in 3 fractions in 8 days. Method of respiratory gating and CyberKnife were used. Follow-up ranges from 1 to 12 months. Results  Early 3-months results show 64% regression (14 cases), 4% stagnation (1 case) and 32% progression (7- cases). However, total dose of 45 Gy does not result in early complete regression. Even in case of  „twin tumores” with the same initial volume (the same initial numer of cancer cells) suprisingly showed different response: regression vs progression what is difficult to interpret from the radiobiological point of view. Conclusion  Total dose of 45 Gy should result in complete regression, but it doesn’t. From theoretical calculation it seem that D10 dose may arise even to 21 Gy what seems not very logical. It can not be excluded that reason for such early  answer  could be „Hallo Phenomenon”- inflamation around irradiated  area suggesting false stagnation or even regression.    EP-1277  Optimising RT dose for anal cancer – the development of three clinical trials in one platform D. Sebag-Montefiore1, R. Adams2, S. Bell3, L. Berkman4, D. Gilbert5, R. Glynne-Joones6, V. Goh7, W. Gregory3, M. Harrison6, L. Kachnic8, M. Lee9, L. McParland3, R. Muirhead10, B. O'Neil11, G. Hutchins1, S. Rao12, A. Renehan13, A. Smith3, G. Velikova1, M. Hawkins14 1Leeds Institute of Cancer and Pathology University of Leeds, Leeds Cancer Centre, Leeds, United Kingdom 2Cardiff University and School of Medicine, Velindre Hospital, Cardiff, United Kingdom 3Leeds Institute of Clinical Trials Research, Clinical Trials Research Unit, Leeds, United Kingdom 4NCRI, Consumer Forum, London, United Kingdom S686                                                                                     ESTRO 36  _______________________________________________________________________________________________   5Royal Sussex County Hospital, Sussex Cancer Centre, Brighton, United Kingdom 6Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, United Kingdom 7Kings College London, Division of Imaging Sciences and Biomedical Engineering, London, United Kingdom 8Vanderbilt University, Department of Radiation Oncology, Nashville, United Kingdom 9Liverpool Hospital, Department of Radiation Oncology, New South Wales, Australia 10University of Oxford, CRUk MRC Oxford Institute for Radiation Oncology, Oxford, United Kingdom 11Beaumont Hospital, St Luke's Radiation Oncology Centre, Dublin, Ireland 12Royal Marsden NHS Trust, Medical Oncology, London, United Kingdom 13University of Manchester, Department of Surgery, Manchester, United Kingdom 14University of Oxford, CRUK MRC Oxford Institute for Radiation Oncology, London, United Kingdom  Purpose or Objective  Previous phase III trials of squamous cell cancer of the anus have determined radiotherapy with concurrent Mitomycin C and 5FU as the standard of care. This did not change with RTOG 9811 and ACT2. Following the development of IMRT guidance we decided to explore radiotherapy questions in future trials across the loco-regional disease spectrum. Material and Methods  We formed a network of UK and international multi-disciplinary trialists and identified the following research questions:- i] can a highly selective policy of involved field CRT result in low locoregional failure (LRF) in small anal margin tumours treated by local excision? ii] can reduced dose CRT using IMRT achieve an acceptably low rate of LRF in early stage anal cancer? iii] can radiotherapy dose escalation reduce the LRF rate with acceptable toxicity in locally advanced disease? Results  The PLATO (PersonaLisingrAdioTherapydOse in anal cancer) is a platform trial comprising of the ACT3, 4 and 5 trials and funded by Cancer Research UK. It is due to commence recruitment in Q4 2016.The ACT 3 trial (n=90) is a non randomised phase II study that will evaluate a strategy of local excision for T1N0 anal margin tumours with selective post operative involved field CRT using 41.4Gy in 23 fractions (F) and concurrent capecitabine, reserved for patients with margins <=1mm. An exact single-stage A’Hern design is used. The ACT4 trial (n=162) is a randomised phase II trial (2:1) comparing reduced dose CRT with 41.4Gy in 23F to GTV with 50.4Gy in 28F using concurrent capecitabine for T1-2(<4cm)N0 disease with IMRT and elective nodal irradiation. An exact single-stage A’Hern design is used. The ACT5 trial (n=640) is a seamless pilot (n=60)/phase II (n=140)/phase III trial (n=640 total) that will compare 53.2Gy with 58.8Gy and 61.6Gy using 28 fractions to GTV with either 5FU or capecitabine in T3/4 N1-3 disease. Toxicity and response will be reported for both the pilot and phase II components. Only one of the dose escalated experimental arms will be evaluated for the phase III component. The primary end point for each trial is 3 year LRF. Conclusion  The PLATO trial concept is efficient with a single funding application and protocol but supports three separate clinical trials. There are clinical leads for each trial. For the patient there is a single patient information sheet for the specific trial relevant to their disease stage. This approach is increasingly important in the era of personalised medicine. Sharing the details of this concept should assist other investigators to develop similar future studies in other disease sites. It is also a template that may assist similar parallel trials to be deigned in other countries.    EP-1278  FMISO-PET &amp; perfusion CT at baseline and; week 2 CRT as predictive markers for response in rectal ca T. Greenhalgh1, J. Wilson2, T. Puri1, J. Franklin1, L. Wang3, R. Goldin4, K. Chu1, V. Strauss5, M. Partridge1, T. Maughan1 1University of Oxford, Department of Oncology, Oxford, United Kingdom 2The Royal Marsden NHS Foundation Trust, Institute of Cancer Research, London, United Kingdom 3Oxford University Hospitals NHS Foundation Trust, Department of Pathology, Oxford, United Kingdom 4Imperial College London, Centre for Pathology, London, United Kingdom 5University of Oxford, Centre for Statistics in Medicine- Oxford Clinical Trials and Research Unit, Oxford, United Kingdom  Purpose or Objective  Patients with locally advanced rectal cancer are considered for neoadjuvant CRT. Around 15% have a complete response with a similar proportion having minimal response. This study explores the predictive value of FMISO-PET and perfusion CT (pCT). Material and Methods  Patients having neoadjuvant CRT for rectal cancer were recruited at a single centre from October 2013-April 2016. FMISO-PET and pCT were done at baseline and in week 2 CRT. Tumour was delineated on MRI by a radiologist, copied to CT using rigid registration and amended for air. FMISO SUVmax in tumour (T) and muscle (M), and perfusion parameters Blood Volume (BV) and Blood Flow (BF) were determined. Pathological tumour regression grade was scored by AJCC 7.0. Results  11 patients were recruited with median age 67 (interquartile range (IQR) 19). 9(82%) were male. Staging was T2 in 2 (18%) and T3 in 9 (92%). 4 (36%) were node negative, 6 (55%) N1 and 1 (9%) N2. All had M0 disease. 7 patients had total mesorectal excision. 7 patients were classed as good responders (AJCC 0/1 or good clinical response) and 4 as poor responders (AJCC 2/3 or poor clinical response).  FMISO scans were evaluable in 8/10 patients at baseline and in 8/9 at week 2 CRT (Table 1). Reasons for unevaluability were non-tumour uptake either in the colorectal lumen, which was maximal on the 4 hour scan due to colonic excretion of FMISO, or through spill in from adjacent bladder activity. Using a threshold of T:M SUVmax ratio of > 1.3, a hypoxic tumour volume was identified at baseline in 7/8 and in 5/8 at week 2 CRT. Baseline median T:M SUVmax was 3.1 (interquartile range (IQR) 1.3). In 5/7 patients with paired evaluable scans, the T:M ratio reduced (≥25% reduction in SUV max), however this showed no correlation with outcome in this small dataset.  All patients had evaluable pCT at baseline and week 2 CRT. Neither baseline median BV (3.2, IQR 2.1) nor BF (23.2, IQR 18) showed a relationship with response. There was also no clear trend for change at week 2 CRT in median BV (2.8, IQR 2.2)) or BF (21, IQR 38.3)). An example FMISO-PET/CT and BV pCT map at baseline and week 2 CRT is shown in Figure 1. 

https://ora.ox.ac.uk/objects/uuid:39d74933-7319-47b8-b14f-c88bef2683f2/files/mef9226442bc01bde7e953947c98872b0

Optimising RT dose for anal cancer - the development of three clinical trials in one platform

Abstract

Similar works

Full text

Available Versions

Crossref

ORA - Oxford University Research Archive

Oxford University Research Archive