Rationale: The UKW3 trial compared biopsy/pre-operative chemotherapy immediate nephrectomy and afforded the opportunity to examine the influence of ous retroperitoneal biopsy and other factors on local and distant relapse of Wilms (WT).Methods: Patients with unilateral WT (stages I-IV) excluding metachronous relapse or progressive disease were eligible. Metastatic and 'inoperable' tumours were biopsied 'Local' was defined as relapse within the abdomen, except for liver metastases considered 'distant' relapse, together with other haematogenous routes. Uni- and multivariable estimated the risk factors for relapse.Results: Overall, 285/635 (44.9%) patients had a biopsy. With a median follow-up 10.1 years, 35 (5.5%) patients experienced a 'local', 15 a combined (2.4%) and 60 (9.4%) a 'distant' relapse. On univariate analysis, biopsy, anaplasia and tumour size were associated an increased risk of local relapse. On multivariable analysis, anaplasia and tumour remained significant for local relapse whereas the elevated risk of biopsy (hazards (HR) = 1.80: 95% confidence interval (CI) 0.97-3.32, p = 0.060) was marginal. Age, anaplasia, tumour size, lymph nodes metastases and stage, but not biopsy, were individually associated with increased risk of distant relapse but only age and anaplasia remained significant following multivariable analysis.Conclusions: The UKW3 trial provides some reassurance that biopsy should not automatically lead to 'upstaging' of WT. Further assessment of this controversial area is required. Comparison of local relapse rates in a multinational trial in which the United Kingdom (UK) continued the practice of routinely biopsying all patients in contrast to the standard European approach will afford this opportunity and is planned. (C) 2014 Elsevier Ltd. All rights reserved.

In locally advanced rectal cancer (LARC) preoperative chemoradiation (CRT) is the standard of care, but the risk of local recurrence is low with good quality total mesorectal excision (TME), although many still develop metastatic disease. Current challenges in treating rectal cancer include the development of effective organ-preserving approaches and the prevention of subsequent metastatic disease.

Background: Thalidomide has potent anti-inflammatory and anti-angiogenic properties. It was evaluated in combination with chemotherapy in two randomised placebo-controlled trials in patients with small cell lung cancer (SCLC, n =724) and advanced non-small cell lung cancer (NSCLC, n =722). Neither study demonstrated an improvement in overall survival with the addition of thalidomide to chemotherapy. This study investigated circulating angiogenic biomarkers in a subset of these patients. Methods: Serial plasma samples were collected in a cohort of patients enrolled in these two trials ( n =95). Vascular endothelial growth factor (VEGF), soluble truncated form of VEGF receptor-2 (sVEGFR-2), interleukin-8 (IL-8), tumour necrosis factor- α (TNF- α ), basic fibroblast growth factor (bFGF) and soluble intercellular adhesion molecule-1 (sICAM-1) levels were measured by enzyme-linked immunosorbent assays. Results were correlated with patient clinical data including stage, response rate and progression-free survival (PFS). Results: Baseline biomarker levels were not significantly different between SCLC and NSCLC. For pooled treatment groups, limited stage SCLC was associated with lower baseline VEGF ( P =0.046), sICAM-1 ( P =0.008) and IL-8 ( P =0.070) than extensive stage disease. Low baseline IL-8 was associated with a significantly improved PFS in both SCLC and NSCLC ( P =0.028), and a greater reduction in IL-8 was associated with a significantly improved tumour response ( P =0.035). Baseline angiogenic factor levels, however, did not predict response to thalidomide. Conclusion: Circulating angiogenic biomarkers did not identify patients who benefited from thalidomide treatment.

ABSTRACT Introduction This phase II trial examined combining cetuximab, irinotecan and capecitabine concurrently with RT in the preoperative downstaging of LARC. Methods Patients (pts) had rectal adenocarcinoma with locally advanced/borderline unresectable disease on MRI. KRAS/BRAF was not assessed before treatment. Pts had pelvic RT to 45 Gy in 25 daily fractions over 5 weeks with concurrent oral capecitabine at 650 mg/m2 twice daily 5 days/week. They also received intravenous (IV) cetuximab at 400 mg/m2 one week before RT then weekly at 250 mg/m2 weeks 1-5 of RT plus IV irinotecan weekly at 60 mg/m2 weeks 1-4 of RT. Surgical resection 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.

The first UKCCCR Anal Cancer Trial (1996) demonstrated the benefit of chemoradiation over radiotherapy (RT) alone for treating epidermoid anal cancer, and it became the standard treatment. Patients in this trial have now been followed up for a median of 13 years. A total of 577 patients were randomised to receive RT alone or combined modality therapy using 5-fluorouracil and mitomycin C. All patients were scheduled to receive 45 Gy by external beam irradiation. Patients who responded to treatment were recommended to have boost RT, with either an iridium implant or external beam irradiation. Data on relapse and deaths were obtained until October 2007. Twelve years after treatment, for every 100 patients treated with chemoradiation, there are an expected 25.3 fewer patients with locoregional relapse (95% confidence interval (CI): 17.5–32.0 fewer) and 12.5 fewer anal cancer deaths (95% CI: 4.3–19.7 fewer), compared with 100 patients given RT alone. There was a 9.1% increase in non-anal cancer deaths in the first 5 years of chemoradiation (95% CI +3.6 to +14.6), which disappeared by 10 years. The clear benefit of chemoradiation outweighs an early excess risk of non-anal cancer deaths, and can still be seen 12 years after treatment. Only 11 patients suffered a locoregional relapse as a first event after 5 years, which may influence the choice of end points in future studies.