A. Sun Myint

EXTRA--a multicenter phase II study of chemoradiation using a 5 day per week oral regimen of capecitabine and intravenous mitomycin C in anal cancer.

PURPOSE 5-Fluorouracil (5-FU) + mitomycin C (MMC)-based chemoradiotherapy is standard treatment for patients with epidermoid anal carcinoma. Clinical trials in other cancers have confirmed 5-FU can successfully be replaced by the oral fluoropyrimidine capecitabine. This phase II trial aimed to determine the feasibility, toxicity, and efficacy of capecitabine, MMC and radiotherapy (RT) in anal cancer patients. METHODS AND MATERIALS Radiotherapy comprised the schedule of the UK Anal Cancer Trial (ACT) II trial (50.4 Gy in 28 fractions of 1.8 Gy). With MMC (12 mg/m2) on Day 1 and capecitabine on each RT treatment day in two divided doses (825 mg/m2 b.i.d). The endpoints were complete response at 4 weeks, local control at 6 months and toxicity. RESULTS Thirty-one patients entered the trial. The median age was 61 years (range 45-86) with 14 males and 17 females. Compliance with chemotherapy with no dose interruptions or delays was 68%, and with RT was 81%. Eighteen (58%) patients completed both modalities of treatment as planned. Dose-limiting Grade 3 or 4 diarrhea was seen in 1 of 31 patients. Three patients experienced Grade 3 neutropenia. There were no treatment-related deaths. Four weeks following completion of chemoradiation, 24 patients (77%) had a complete clinical response, and 4 (16%) a partial response. With a median follow-up of 14 months, three locoregional relapses occurred. CONCLUSIONS Capecitabine with MMC and RT in with patients anal carcinoma is well tolerated, with minimal toxicity and acceptable compliance. We recommend testing this schedule in future national Phase III studies in anal cancer.

Multi‐modality approach in curative local treatment of early rectal carcinomas

Objective  Despite recent advances, surgery remains the mainstay for the management of rectal carcinoma. The conventional surgical treatment for low rectal carcinoma is total mesorectal excision. This results in either abdomino‐perineal excision of the rectum (APER) with permanent colostomy or low anterior resection (LAR) usually with a covering stoma. Local resection is an alternative treatment option and this could be offered either using manual trans‐anal resection (TAR) or transanal endoscopic microsurgery (TEM) if the tumour is situated higher.

Can increasing the dose of radiation by HDR brachytherapy boost following pre operative chemoradiotherapy for advanced rectal cancer improve surgical outcomes

Aim  Preoperative radiotherapy has been shown to improve local control in advanced rectal carcinoma compared with surgery alone. Several large randomized trials have confirmed that chemoradiotherapy (CRT) is better than radiotherapy alone. This pilot study was designed to increase the radiation dose using high‐dose rate (HDR) brachytherapy boost following preoperative CRT to evaluate whether this strategy improves the outcome of surgery without increase in toxicity.

Preoperative chemoradiotherapy for rectal cancer: a comparison between intravenous 5-fluorouracil and oral capecitabine

Introduction  Capecitabine provides an attractive alternative to intravenous (IV) 5‐flourouracil (5‐FU) in chemoradiation regimes for rectal cancer by avoiding the need for intravenous access and inpatient stay. We aimed to compare retrospectively the efficacy of concurrent capecitabine with IV 5‐FU in preoperative pelvic chemoradiation schedules for rectal cancer in our centre.

Preoperative neo‐adjuvant therapy for curable rectal cancer – reaching a consensus 2008

Objective  Our aim was to determine the range of neo‐adjuvant therapy the multidisciplinary team (MDT) currently offers patients with curable (M0) rectal cancer.

Irinotecan+5-fluorouracil with concomitant pre-operative radiotherapy in locally advanced non-resectable rectal cancer: a phase I/II study.

In the UK, 10% of patients diagnosed with rectal cancer have inoperable disease at presentation. This study ascertained whether the resectability rate of inoperable locally advanced rectal cancer was improved by administration of intravenous irinotecan, 5-fluorouracil (5-FU) and pelvic radiotherapy. During phase I of the trial (n=12), the dose of irinotecan was escalated in three-patient cohorts from 50 mg m−2 to 60 mg m−2 to 70 mg m−2 to identify the maximum tolerated dose (60 mg m−2). In phase II, 31 patients with non-resectable disease received 45 Gy radiotherapy and 5-FU infusions (200 mg m−2 per day) for 5 weeks. Irinotecan (60 mg m−2) was given on days 1, 8, 15 and 22. After treatment, patients were operated on if possible. Thirty patients completed the protocol, 28 underwent surgery. Before surgery, MRI restaging of 24 patients showed that 19 (79%) had a reduction in tumour stage after treatment (seven complete clinical response and 12 partial). Of 27 patients followed up after surgery, 22 (81%) had clear circumferential resection margins. Disease-free and overall survival estimates at 3 years were 65 and 90%, respectively. The regimen was well tolerated. Irinotecan, 5-FU and radiotherapy results in tumour downgrading, allowing resection of previously inoperable tumour with acceptable toxicity.

Contact radiotherapy boost in association with 'watch and wait' for rectal cancer: initial experience and outcomes from a shared programme between a district general hospital network and a regional oncology centre.

Recent data have highlighted the potential of more intensive neoadjuvant protocols to increase and sustain the rate of complete response in rectal cancer managed nonoperatively. This study aimed to review the outcome of all patients from our district general hospitals network who had received standard neoadjuvant therapy and were additionally referred to a centre of excellence for contact X‐ray brachytherapy or high‐dose‐rate brachytherapy boost.

Follow up: Follow up guidelines

Anal cancer is a rare disease, accounting for 1–2% of gastrointestinal malignancies. Therefore, the number of cases requiring follow up is relatively small at each centre. NICE guidelines on improving outcomes in colorectal cancer suggest site specialisation for anal cancer. Most cancer networks has now set up ‘Anal cancer MDT’ and the person responsible for follow up should be one, preferably two members of the MDT who specialise in the treatment of anal cancer. This has ensured the necessary expertise to develop in the follow up and the management of patients with anal cancer. Following the publication of the results of UKCCCR anal cancer ACT 1 trial, chemoradiotherapy is now regarded as the standard treatment for anal cancer [1]. It is offered to most patients except for very old and frail patients where modified dose of radiotherapy alone was used. The results of the ACT 2 trial presented at the ASCO (2009) showed that the local control rates for all stages were very high (95%) [2]. The earlier stage disease obviously resulted in much better outcomes. Distant relapse is not very common and for the few patients who failed locally, radical salvage surgery offers the best chance of long term cure. Therefore, regular follow up is necessary to identify patients who can be salvage: 1 Those with loco-regional persistent disease following chemoradiotherapy. 2 Those with subsequent loco-regional failure without distant metastases. These patients must be discussed at the regional anal cancer MDT and salvage surgery performed by designated experience surgeons with special interest who are members of the regional anal cancer MDT. Patients with anal cancer treated should be divided into low and high risk cases. The investigations carried out during follow up period depend on the predicted risk of recurrence.

Contact X-ray Brachytherapy as an Adjunct to a Watch and Wait Approach is an Affordable Alternative to Standard Surgical Management of Rectal Cancer for Patients with a Partial Clinical Response to Chemoradiotherapy

AIMS Emerging evidence suggests that contact X-ray brachytherapy (CXB) may increase the clinical complete response rate and durability when administered after standard chemoradiotherapy in patients with rectal cancer. The addition of CXB in partial responders is therefore probably cost-effective. The affordability of widening access to CXB in the UK, however, has not been evaluated. MATERIALS AND METHODS Decision analytical modelling with Monte Carlo simulation was used to evaluate long-term costs for the management of patients with rectal cancers who were given a CXB boost when a clinical complete response was not initially achieved following chemoradiotherapy in order to facilitate a watch and wait approach. A third-party payer (National Health Service) perspective was adopted, probabilistic sensitivity analysis was carried out and a scenario analysis was performed to investigate the effect of the number of referral centres and number of patients treated with CXB. RESULTS We estimate that 818 (95% confidence interval 628-1021) patients per year are eligible for CXB as an adjunct to a watch and wait approach in England and Wales. As this management is less costly than surgical management for each individual patient, the more patients treated, the more affordable the technology. Even if as few as 125 patients are treated nationally in 15 centres, the cost of implementing this technology would be less than £4 million. If the average number of patients treated in each centre is 30, this technology would be cost saving within 5 years. CONCLUSIONS The cost of CXB is not prohibitive according to the National Institute for Health and Care Excellence threshold for implementation of new technology and may even be cost saving within 5 years compared with standard surgical management, depending on the uptake of the technology and the number of referral centres.