Search

Total mesorectal excision is the cornerstone of treatment for rectal cancer. Multiple randomised trials have shown a reduction in local recurrence rates with the addition of preoperative radiotherapy, either as a 1-week hypofractionated short-course (SCRT) or a conventionally fractionated long-course (LCRT) schedule with concurrent chemotherapy. There is also increasing interest in the addition of neoadjuvant chemotherapy to radiotherapy with the aim of improving disease-free survival. The relative use of SCRT and LCRT varies considerably across the world. This is reflected in, and is probably driven in part by, disparity between international guideline recommendations. In addition, different approaches to treatment may exist both between and within countries, with variation related to patient, disease and treatment centre and financial factors. In this review, we will specifically focus on the use of SCRT for the treatment of rectal cancer. We will discuss the literature base and current guidelines, highlighting the challenges and controversies in clinical application of this evidence. We will also discuss potential future applications of SCRT, including its role in optimisation and intensification of treatment for rectal cancer.

Pre-trial radiotherapy quality assurance (RTQA) for the SPARC trial of preoperative pancreas SBRT highlighted overgenerous target contouring. We aimed to assess for improvement following a training workshop and appraise the effectiveness of a novel web-conferencing format for on-trial RTQA.

The UK led PersonaLising Anal cancer radioTherapy dOse(PLATO) is a complex integrated protocol, consisting of 3 distinct anal cancer trials. Anal cancer IMRT contouring is challenging as there are several nodal areas that are electively irradiated and the primary tumour is not well visualised on CT. We identified FALCON, an ESTRO supported multifunctional online contouring platform (EduCase), aimed at reducing contouring variability, as a method to streamline pre-trial radiotherapy (RT) quality assurance (QA). Investigators contoured a benchmark case using FALCON prior to attending workshops aimed at evaluating contouring variation and refining the trial RT protocol. We present qualitative feedback received from workshop participants. We also present conformity analysis of contours compared with a reference contour.

The objective of this study was to evaluate the maximum tolerated dose (MTD) and recommended dose of irinotecan administered as a 5-day schedule synchronously with 5-fluorouracil (5FU), leucovorin (LV) and preoperative pelvic radiation (45 Gy) for primary borderline/unresectable, locally advanced rectal cancer. The study used escalating doses of intravenous irinotecan (6, 8, 10, 12, 14, 16, 18, and 20 mg m(-2)) administered on days 1-5 and 29-33 followed by low dose LV (20 mg m(-2)) and 5FU (350 mg m(-2) over 1 h) in sequential cohorts. Preoperative pelvic radiotherapy using a three- or four-field technique and megavoltage photons comprised 45 Gy given in 25 fractions, 1.8 Gy per fraction. Surgery in the form of mesorectal excision was performed 6-10 weeks later. Histopathological examination of the resected specimen was performed according to techniques of Quirke, and compared with clinical staging. A distance of 1 mm or less between the peripheral extent of the tumour and the radial resection margin defined an involved circumferential resection margin (CRM). The MTD was determined as the dose causing more than a third of patients to have a dose-limiting toxicity (DLT) defined as specific grade 3 or 4 toxicities. Once the MTD was reached, a further 14 patients were treated at the dose level below the MTD. In total, 57 patients received irinotecan at the eight dose levels. The final cohort reached DLT after only four patients had been enrolled. The median age was 62 years (range 26-75), 37 male and 20 female subjects. The MTD of irinotecan in this schedule was 20 mg m(-2) when three out of four patients experienced DLT. Dose limiting grade 3 or 4 diarrhoea was reported in seven out of 57 patients, three at the 20 mg m(-2) dose level. Serious haematological toxicity (grade 3) was minimal and reported in only three patients; one grade 3 neutropaenia, one grade 4 neutropaenia and one grade 3 febrile neutropaenia and anaemia. Compliance was good with 93 and 89% of patients completing radiotherapy and chemotherapy, respectively. The remaining patients had only minor deviations from protocol therapy. Eight patients did not proceed to surgery, in six cases because they remained unresectable or had developed metastatic disease, one patient was unfit for surgery and one died as a result of complications from radiotherapy. Forty-nine patients underwent a potentially curative surgical resection. Histopathological examination of the resected specimen demonstrated pCR 12 out of 49 (24%) and 12 out of 57 (21%) overall. A histologically confirmed clear circumferential resection margin (CRM) was achieved in 39 out of 49 (80%) of those resected, and 39 out of 57 (68%) overall. In conclusion, MTD with this scheduled regimen of irinotecan is 20 mg m(-2) (days 1-5 and 29-33). The acceptable toxicity and compliance at 18 mg m(-2) recommend testing this dose in future phase III studies. The tumour downstaging and complete resection rates (negative CRM) are encouragingly high for this very locally advanced group.

Aims UK guidance was recently developed for the treatment of anal cancer using intensity-modulated radiotherapy (IMRT). We audited the current use of radiotherapy in UK cancer centres for the treatment of anal cancer against such guidance. We describe the acute toxicity of IMRT in comparison with patient population in the audit treated with two-phase conformal radiotherapy and the previous published data from two-phase conformal radiotherapy, in the UK ACT2 trial. Materials and methods A Royal College of Radiologists' prospective national audit of patients treated with radiotherapy in UK cancer centres was carried out over a 6 month period between February and July 2015. Results Two hundred and forty-two cases were received from 40/56 cancer centres (71%). In total, 231 (95%) underwent full dose radiotherapy with prophylactic nodal irradiation. Of these, 180 (78%) received IMRT or equivalent, 52 (22%) two-phase conformal (ACT2) technique. The number of interruptions in radiotherapy treatment in the ACT2 trial was 15%. Interruptions were noted in 7% (95% confidence interval 0–14%) of courses receiving two-phase conformal and 4% (95% confidence interval 1–7%) of those receiving IMRT. The percentage of patients completing the planned radiotherapy dose, irrelevant of gaps, was 90% (95% confidence interval 82–98%) and 96% (95% confidence interval 93–99%), in two-phase conformal and IMRT respectively. The toxicity reported in the ACT2 trial, in patients receiving two-phase conformal in the audit and in patients receiving IMRT in the audit was: any toxic effect 71%, 54%, 48%, non-haematological 62%, 49%, 40% and haematological 26%, 13%, 18%, respectively. Conclusions IMRT implementation for anal cancer is well underway in the UK with most patients receiving IMRT delivery, although its usage is not yet universal. This audit confirms that IMRT results in reduced acute toxicity and minimised treatment interruptions in comparison with previous two-phase conformal techniques., Highlights • Most UK centres deliver IMRT to all or selected anal cancer patients. • IMRT reduced any grade 3 or 4 acute toxic effect in comparison with two-phase conformal from 54% to 48%. • IMRT reduced interruptions in treatment in comparison with two-phase conformal from 7% to 4%. • Completion rate of planned radiotherapy dose in comparison with two-phase conformal from 90% to 96%.

Chemotherapy followed by consolidation chemoradiotherapy (CRT) is a treatment option for locally advanced non-metastatic pancreatic cancer (LAPC), but outcome remains poor. The SCALOP trial identified a feasible, safe, and effective CRT regimen for LAPC: capecitabine (830mg/m2 oral bd) as radiosensitisation + 50.4Gy in 28 fractions. The two-stage SCALOP-2 trial aims to improve this regimen by increasing radiotherapy dose intensity and adding nelfinavir as an additional radiosensitising AKT inhibitor.

A few patients with anal cancer will require a defunctioning stoma prior to chemoradiotherapy (CRT). The purpose of this retrospective review was to determine the frequency with which a pretreatment stoma was subsequently reversed.Between 1997 and 2007, 46/344 patients who were treated for anal cancer underwent a defunctioning stoma prior to CRT. Thirty-five of these were treated with curative intent.Of the 35 patients, 16 patients had T4, 17 T3 and 2 T2 disease. Sixteen were node positive. The average tumour size was 7 cm. The median interval between stoma formation and CRT was 6 (4-20) weeks. The median follow up was 26 (2-80) months. A defunctioning stoma was performed for rectovaginal fistula or risk of fistula in 18 and severe local symptoms in 17. Seven (20%) patients had the stoma reversed subsequently. The reasons for nonreversal were progressive disease (n = 9), persistent fistula (n = 3), predicted poor function (n = 4), cavity formation (n = 1), fibrosis (n = 3), death from another cause (n = 2), patient choice (n = 3) and salvage surgery (n = 2). The overall 3-year survival was only 48%, explained by the advanced stage of disease at presentation.Most patients who undergo a defunctioning stoma before CRT will not undergo subsequent reversal. The patient should therefore be informed that the stoma is likely to be permanent and this should be taken into account when considering the type and site of stoma to be formed.

3 Background: NEOSCOPE compared toxicity and efficacy of 2 pre-op CRT regimens. Methods: Eligibility: Resectable ACA of the oesophagus/GOJ ≥ T3 and/or ≥ N1. Randomisation: 1:1 to OXCAP-CRT (oxaliplatin 85 mg/m2 Day 1,15,29; capecitabine 625 mg/m2 bd on days of RT) or CarPac-CRT (Carboplatin AUC2; paclitaxel 50 mg/m2 Day 1,8,15,22,29); concurrent RT: 45Gy/25 fractions/5 weeks. Both arms received induction chemo: 2 cycles of OXCAP (oxaliplatin 130 mg/m2 D1, Cape 625 mg/m2D1-21, q 3wk). Surgery: 6-8 weeks after naCRT. Detailed RT and pathology quality assurance was built into the protocol. Primary end-point: pathological complete response (pCR). Secondary: toxicity, surgical morbidity/mortality, R1 rate, OS. Statistics: A pCR of 15% would not warrant further investigation but a pCR of 35% would. 76 patients (38/arm) gave 90% power and one-sided type I error of 10% meaning that either arm having ≥10 pCR out of first 38 patients would be considered for Phase III. 85 patients to be recruited (allows 10% loss to follow up). Results: 85 patients were randomised between Oct 2013 and Feb 2015 from 17 UK centres. Patient characteristics: median age 65 yrs, Male (81%), WHO PS 0 (85%). Tumour characteristics: T3 (86%), N1 (48%), lower third/GOJ (90%), median tumour length 5.8cm. CTCAE grade 3/4 toxicity rate during CRT was OXCAP-CRT 42.1%, CarPac-CRT 52.4% (p=0.358). Protocol dose RT OXCAP-CRT 90.5%, CarPac-CRT 93%. Conclusion:Both regimens were well tolerated. CarPac-CRT passed the criteria for taking forward to a phase III study but OXCAP-RT did not. Funding: Cancer Research UK (C44694/A14614), ClinicalTrials.gov: NCT01843829, coordinated by Wales Cancer Trials Unit. Clinical trial information: NCT01843829. [Table: see text]

Limited knowledge causes variation in practice

DOSE ESCALATION STUDY USING 4D CT PLANNING IN LOCALLY ADVANCED PANCREATIC CANCER G. Radhakrishna1, M. collins1, S. Wilson1, D. Sebag-Montefiore1, B. Carey1, S. Swift1, K. Franks1, J. Lilley2, D. Smith1, S. Kirwin1, R. Lindsay1, H. Summers1, A. Woolley1, P. Byrne1, N. Roberts1, J. Sykes1, A. Needham1, A. M. Crellin1 1 ST JAMES INSTITUTE OF ONCOLOGY THE LEEDS TEACHING HOSPITALS NHS TRUST, Leeds, United Kingdom 2 ST JAMES’S INSTITUTE OF ONCOLOGY, Leeds, United Kingdom

screen in the CCD camera field of view and firmly hold in place. Whenever the source is in the CCD field of view and the room light is turned off, a fluorescent halo due to the source radiation is clearly visible on the screen and recorded by the camera. Source dwell position and time as well as source transit speed are then deducted from that halo by means of an automated source position recognition algorithm. As results of the analysis, QuoVadis returns the estimated source transit speed, measured dwell positions, measured dwell times, differences between measured and reference values and their comparison with tolerance values.In this study, brachytherapy irradiations were performed by means of a 18 channels Microselectron HDR remote afterloading device. To validate QuoVadis, the inter-frames reproducibility of the automated source position recognition algorithm was evaluated and QA measurements were performed and compared to reference values of all the 18 channels. Results: Mean and median differences of the location of a standing source over 891 images were both of 0.02±0.01mm, respectively, resulting in a very high reproducibility of the source dwell position recognition on each image frame. The reported figure shows the planar distribution (in millimetres) of all the obtained positions of the standing source.