Yttrium-90 Transarterial Radioembolization for Chemotherapy-Refractory Intrahepatic Cholangiocarcinoma: A Prospective, Observational Study.

PURPOSE: To evaluate the safety and efficacy of yttrium-90 transarterial radioembolization (TARE) for the treatment of unresectable, chemotherapy-refractory intrahepatic cholangiocarcinoma (ICC). METHODS: A prospective, observational study was carried out in 10 centers between 2013 and 2017. TARE plus standard care was delivered to patients with unresectable, chemotherapy-refractory or chemotherapy-intolerant ICC. Primary outcome was overall survival. Secondary outcomes included safety, progression-free survival (PFS), and liver-specific progression-free survival (LPFS). RESULTS: Sixty-one patients were treated with TARE. Patients were 53% male; median age was 64 years; 91% had performance status 0/1; 92% had received prior chemotherapy; and 59% had no extrahepatic disease. Median follow-up was 13.9 months (95% confidence interval [CI], 9.6-18.1). Overall survival was 8.7 months (95% CI, 5.3-12.1), and 37% of patients survived to 12 months. PFS was 2.8 months (95% CI, 2.6-3.1), and LPFS was 3.1 months (95% CI, 1.3-4.8). One severe complication (abdominal pain) occurred at the time of the TARE procedure. Thirty patients experienced a total of 49 adverse events, of which 8% were grade ≥3; most common were grade 1-2 fatigue and abdominal pain. A total of 77 abnormal laboratory value events were recorded, of which 4% were grade ≥3. CONCLUSIONS: Patients with advanced ICC have limited therapeutic options and a poor prognosis. This prospective study examined the survival of patients with unresectable, chemotherapy-refractory primary ICC treated with TARE in real-world practice. The results demonstrate that this treatment merits further investigation in this patient cohort in a larger study, including collection of patient-reported outcomes.

Neoadjuvant cisplatin and fluorouracil versus epirubicin, cisplatin, and capecitabine followed by resection in patients with oesophageal adenocarcinoma (UK MRC OE05): an open-label, randomised phase 3 trial.

BACKGROUND: Neoadjuvant chemotherapy before surgery improves survival compared with surgery alone for patients with oesophageal cancer. The OE05 trial assessed whether increasing the duration and intensity of neoadjuvant chemotherapy further improved survival compared with the current standard regimen. METHODS: OE05 was an open-label, phase 3, randomised clinical trial. Patients with surgically resectable oesophageal adenocarcinoma classified as stage cT1N1, cT2N1, cT3N0/N1, or cT4N0/N1 were recruited from 72 UK hospitals. Eligibility criteria included WHO performance status 0 or 1, adequate respiratory, cardiac, and liver function, white blood cell count at least 3 × 109 cells per L, platelet count at least 100 × 109 platelets per L, and a glomerular filtration rate at least 60 mL/min. Participants were randomly allocated (1:1) using a computerised minimisation program with a random element and stratified by centre and tumour stage, to receive two cycles of cisplatin and fluorouracil (CF; two 3-weekly cycles of cisplatin [80 mg/m2 intravenously on day 1] and fluorouracil [1 g/m2 per day intravenously on days 1-4]) or four cycles of epirubicin, cisplatin, and capecitabine (ECX; four 3-weekly cycles of epirubicin [50 mg/m2] and cisplatin [60 mg/m2] intravenously on day 1, and capecitabine [1250 mg/m2] daily throughout the four cycles) before surgery, stratified according to centre and clinical disease stage. Neither patients nor study staff were masked to treatment allocation. Two-phase oesophagectomy with two-field (abdomen and thorax) lymphadenectomy was done within 4-6 weeks of completion of chemotherapy. The primary outcome measure was overall survival, and primary and safety analyses were done in the intention-to-treat population. This trial is registered with the ISRCTN registry (number 01852072) and ClinicalTrials.gov (NCT00041262), and is completed. FINDINGS: Between Jan 13, 2005, and Oct 31, 2011, 897 patients were recruited and 451 were assigned to the CF group and 446 to the ECX group. By Nov 14, 2016, 327 (73%) of 451 patients in the CF group and 302 (68%) of 446 in the ECX group had died. Median survival was 23·4 months (95% CI 20·6-26·3) with CF and 26·1 months (22·5-29·7) with ECX (hazard ratio 0·90 (95% CI 0·77-1·05, p=0·19). No unexpected chemotherapy toxicity was seen, and neutropenia was the most commonly reported event (grade 3 or 4 neutropenia: 74 [17%] of 446 patients in the CF group vs 101 [23%] of 441 people in the ECX group). The proportions of patients with postoperative complications (224 [56%] of 398 people for whom data were available in the CF group and 233 [62%] of 374 in the ECX group; p=0·089) were similar between the two groups. One patient in the ECX group died of suspected treatment-related neutropenic sepsis. INTERPRETATION: Four cycles of neoadjuvant ECX compared with two cycles of CF did not increase survival, and cannot be considered standard of care. Our study involved a large number of centres and detailed protocol with comprehensive prospective assessment of health-related quality of life in a patient population confined to people with adenocarcinomas of the oesophagus and gastro-oesophageal junction (Siewert types 1 and 2). Alternative chemotherapy regimens and neoadjuvant chemoradiation are being investigated to improve outcomes for patients with oesophageal carcinoma. FUNDING: Cancer Research UK and Medical Research Council Clinical Trials Unit at University College London.

Clinical outcomes following proton therapy for children with central nervous system tumors referred overseas.

BACKGROUND: International, multidisciplinary care of children with central nervous system (CNS) tumors presents unique challenges. The aim of this study is to report patient outcomes of U.K. children referred for proton therapy to a North American facility. METHODS: From 2008 to 2016, 166 U.K. children with approved CNS tumors were treated with proton therapy at a single academic medical center in the United States. Median age was 7 years (range, 1-19). Median follow-up was 2.6 years. RESULTS: The 3-year actuarial overall survival (OS) and local control (LC) rates were 96% and 91%, respectively, for the overall group, 92% and 85% for the ependymoma subgroup (n = 57), 95% and 88% for the low-grade glioma subgroup (n = 54), and 100% and 100%, respectively, for the craniopharyngioma subgroup (n = 45). Cyst expansion was observed in 13 patients, including one case resulting in visual impairment. Serious side effects included new-onset seizures in three patients (1.8%), symptomatic vasculopathy in three patients (1.8%), and symptomatic brainstem necrosis in one patient (0.6%). CONCLUSIONS: In this cohort of British children referred overseas for proton therapy, disease control does not appear compromised, toxicity is acceptable, and improvement in long-term function is anticipated in survivors owing to the reduced brain exposure afforded by proton therapy.

Position statement on ethics, equipoise and research on charged particle radiation therapy.

The use of charged-particle radiation therapy (CPRT) is an increasingly important development in the treatment of cancer. One of the most pressing controversies about the use of this technology is whether randomised controlled trials are required before this form of treatment can be considered to be the treatment of choice for a wide range of indications. Equipoise is the key ethical concept in determining which research studies are justified. However, there is a good deal of disagreement about how this concept is best understood and applied in the specific case of CPRT. This report is a position statement on these controversies that arises out of a workshop held at Wolfson College, Oxford in August 2011. The workshop brought together international leaders in the relevant fields (radiation oncology, medical physics, radiobiology, research ethics and methodology), including proponents on both sides of the debate, in order to make significant progress on the ethical issues associated with CPRT research. This position statement provides an ethical platform for future research and should enable further work to be done in developing international coordinated programmes of research.

Proton Beam Therapy in the Oligometastatic/Oligorecurrent Setting: Is There a Role? A Literature Review.

BACKGROUND: Stereotactic ablative radiotherapy (SABR) and stereotactic radiosurgery (SRS) with conventional photon radiotherapy (XRT) are well-established treatment options for selected patients with oligometastatic/oligorecurrent disease. The use of PBT for SABR-SRS is attractive given the property of a lack of exit dose. The aim of this review is to evaluate the role and current utilisation of PBT in the oligometastatic/oligorecurrent setting. METHODS: Using Medline and Embase, a comprehensive literature review was conducted following the PICO (Patients, Intervention, Comparison, and Outcomes) criteria, which returned 83 records. After screening, 16 records were deemed to be relevant and included in the review. RESULTS: Six of the sixteen records analysed originated in Japan, six in the USA, and four in Europe. The focus was oligometastatic disease in 12, oligorecurrence in 3, and both in 1. Most of the studies analysed (12/16) were retrospective cohorts or case reports, two were phase II clinical trials, one was a literature review, and one study discussed the pros and cons of PBT in these settings. The studies presented in this review included a total of 925 patients. The metastatic sites analysed in these articles were the liver (4/16), lungs (3/16), thoracic lymph nodes (2/16), bone (2/16), brain (1/16), pelvis (1/16), and various sites in 2/16. CONCLUSIONS: PBT could represent an option for the treatment of oligometastatic/oligorecurrent disease in patients with a low metastatic burden. Nevertheless, due to its limited availability, PBT has traditionally been funded for selected tumour indications that are defined as curable. The availability of new systemic therapies has widened this definition. This, together with the exponential growth of PBT capacity worldwide, will potentially redefine its commissioning to include selected patients with oligometastatic/oligorecurrent disease. To date, PBT has been used with encouraging results for the treatment of liver metastases. However, PBT could be an option in those cases in which the reduced radiation exposure to normal tissues leads to a clinically significant reduction in treatment-related toxicities.

Estimating the percentage of patients who might benefit from proton beam therapy instead of X-ray radiotherapy.

OBJECTIVES: High-energy Proton Beam Therapy (PBT) commenced in England in 2018 and NHS England commissions PBT for 1.5% of patients receiving radical radiotherapy. We sought expert opinion on the level of provision. METHODS: Invitations were sent to 41 colleagues working in PBT, most at one UK centre, to contribute by completing a spreadsheet. 39 responded: 23 (59%) completed the spreadsheet; 16 (41%) declined, arguing that clinical outcome data are lacking, but joined six additional site-specialist oncologists for two consensus meetings. The spreadsheet was pre-populated with incidence data from Cancer Research UK and radiotherapy use data from the National Cancer Registration and Analysis Service. 'Mechanisms of Benefit' of reduced growth impairment, reduced toxicity, dose escalation and reduced second cancer risk were examined. RESULTS: The most reliable figure for percentage of radical radiotherapy patients likely to benefit from PBT was that agreed by 95% of the 23 respondents at 4.3%, slightly larger than current provision. The median was 15% (range 4-92%) and consensus median 13%. The biggest estimated potential benefit was from reducing toxicity, median benefit to 15% (range 4-92%), followed by dose escalation median 3% (range 0 to 47%); consensus values were 12 and 3%. Reduced growth impairment and reduced second cancer risk were calculated to benefit 0.5% and 0.1%. CONCLUSIONS: The most secure estimate of percentage benefit was 4.3% but insufficient clinical outcome data exist for confident estimates. The study supports the NHS approach of using the evidence base and developing it through randomised trials, non-randomised studies and outcomes tracking. ADVANCES IN KNOWLEDGE: Less is known about the percentage of patients who may benefit from PBT than is generally acknowledged. Expert opinion varies widely. Insufficient clinical outcome data exist to provide robust estimates. Considerable further work is needed to address this, including international collaboration; much is already underway but will take time to provide mature data.

WITHDRAWN: Interventions for dysphagia in oesophageal cancer.

BACKGROUND: The majority of oesophageal and gastro-oesophageal cancers are diagnosed at an advanced stage and palliative treatment is the realistic management option for most patients. The optimal intervention for the palliation of dysphagia in these patients has not been established. OBJECTIVES: To systematically analyse and summarise the efficacy of different interventions used in the palliation of dysphagia in primary oesophageal carcinoma. SEARCH STRATEGY: We undertook a search according to the Cochrane Upper Gastrointestinal and Pancreatic Diseases model using the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE and CINAHL and major conference proceedings up to August 2005. The literature search was re-run in August 2006 and March 2007. SELECTION CRITERIA: Randomised controlled trials (RCTs) in patients with inoperable or unresectable primary oesophageal cancer who underwent palliative treatment. We included rigid plastic intubation, self-expanding metallic stent (SEMS) insertion, brachytherapy, external beam radiotherapy, chemotherapy, oesophageal bypass surgery, chemical and thermal ablation therapy, either head-to-head or in combination. The primary outcome was dysphagia improvement. Secondary outcomes included recurrent dysphagia, technical success, procedure related mortality, 30-day mortality, adverse effects and quality of life. DATA COLLECTION AND ANALYSIS: One author assessed the eligibility criteria of each study and extracted data regarding outcomes and factors affecting risk of bias. MAIN RESULTS: We included 2542 patients from 40 studies. SEMS insertion is safer and more effective than plastic tube insertion. Thermal and chemical ablative therapy provide comparable dysphagia palliation but have an increased requirement for re-interventions and adverse effects. Anti-reflux stents provide comparable dysphagia palliation to conventional metal stents. Some anti-reflux stents might reduce gastro-oesophageal reflux compared to conventional metal stents. Brachytherapy might be a suitable alternative to SEMS in providing a survival advantage and possibly a better quality of life. AUTHORS' CONCLUSIONS: Self-expanding metal stent insertion is safe, effective and quicker in palliating dysphagia compared to other modalities. However, high-dose intraluminal brachytherapy is a suitable alternative and might provide additional survival benefit with a better quality of life. Self-expanding metal stent insertion and brachytherapy provide comparable palliation to endoscopic ablative therapy but are preferable due to the reduced requirement for re-interventions. Rigid plastic tube insertion, dilatation alone or in combination with other modalities, chemotherapy alone, combination chemoradiotherapy and bypass surgery are not recommended for palliation of dysphagia due to a high incidence of delayed complications and recurrent dysphagia.

Heavy charged particle beam therapy and related new radiotherapy technologies: The clinical potential, physics and technical developments required to deliver benefit for patients with cancer.

In the UK, one in two people will develop cancer during their lifetimes and radiotherapy (RT) plays a key role in effective treatment. High energy proton beam therapy commenced in the UK National Health Service in 2018. Heavier charged particles have potential advantages over protons by delivering more dose in the Bragg peak, with a sharper penumbra, lower oxygen dependence and increased biological effectiveness. However, they also require more costly equipment including larger gantries to deliver the treatment. There are significant uncertainties in the modelling of relative biological effectiveness and the effects of the fragmentation tail which can deliver dose beyond the Bragg peak. These effects need to be carefully considered especially in relation to long-term outcomes.In 2019, a group of clinicians, clinical scientists, engineers, physical and life scientists from academia and industry, together with funding agency stakeholders, met to consider how the UK should address new technologies for RT, especially the use of heavier charged particles such as helium and carbon and new modes of delivery such as FLASH and spatially fractionated radiotherapy (SFRT).There was unanimous agreement that the UK should develop a facility for heavier charged particle therapy, perhaps constituting a new National Ion Research Centre to enable research using protons and heavier charged particles. Discussion followed on the scale and features, including which ions should be included, from protons through helium, boron, and lithium to carbon, and even oxygen. The consensus view was that any facility intended to treat patients must be located in a hospital setting while providing dedicated research space for physics, preclinical biology and clinical research with beam lines designed for both in vitro and in vivo research. The facility should to be able to investigate and deliver both ultra-high dose rate FLASH RT and SFRT (GRID, minibeams etc.). Discussion included a number of accelerator design options and whether gantries were required. Other potential collaborations might be exploited, including with space agencies, electronics and global communications industries and the nuclear industry.In preparation for clinical delivery, there may be opportunities to send patients overseas (for 12C or 4He ion therapy) using the model of the National Health Service (NHS) Proton Overseas Programme and to look at potential national clinical trials which include heavier ions, FLASH or SFRT. This could be accomplished under the auspices of NCRI CTRad (National Cancer Research Institute, Clinical and Translational Radiotherapy Research Working Group).The initiative should be a community approach, involving all interested parties with a vision that combines discovery science, a translational research capability and a clinical treatment facility. Barriers to the project and ways to overcome them were discussed. Finally, a set of different scenarios of features with different costs and timelines was constructed, with consideration given to the funding environment (prer-Covid-19) and need for cross-funder collaboration.

Proton beam therapy: perspectives on the National Health Service England clinical service and research programme.

The UK has an important role in the evaluation of proton beam therapy (PBT) and takes its place on the world stage with the opening of the first National Health Service (NHS) PBT centre in Manchester in 2018, and the second in London coming in 2020. Systematic evaluation of the role of PBT is a key objective. By September 2019, 108 patients had started treatment, 60 paediatric, 19 teenagers and young adults and 29 adults. Obtaining robust outcome data is vital, if we are to understand the strengths and weaknesses of current treatment approaches. This is important in demonstrating when PBT will provide an advantage and when it will not, and in quantifying the magnitude of benefit.The UK also has an important part to play in translational PBT research, and building a research capability has always been the vision. We are perfectly placed to perform translational pre-clinical biological and physical experiments in the dedicated research room in Manchester. The nature of DNA damage from proton irradiation is considerably different from X-rays and this needs to be more fully explored. A better understanding is needed of the relative biological effectiveness (RBE) of protons, especially at the end of the Bragg peak, and of the effects on tumour and normal tissue of PBT combined with conventional chemotherapy, targeted drugs and immunomodulatory agents. These experiments can be enhanced by deterministic mathematical models of the molecular and cellular processes of DNA damage response. The fashion of ultra-high dose rate FLASH irradiation also needs to be explored.

Interventions for dysphagia in oesophageal cancer.

BACKGROUND: The majority of oesophageal and gastro-oesophageal cancers are diagnosed at an advanced stage and palliative treatment is the realistic management option for most patients. The optimal intervention for the palliation of dysphagia in these patients has not been established. OBJECTIVES: To systematically analyse and summarise the efficacy of different interventions used in the palliation of dysphagia in primary oesophageal carcinoma. SEARCH STRATEGY: We undertook a search according to the Cochrane Upper Gastrointestinal and Pancreatic Diseases model using the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE and CINAHL and major conference proceedings up to August 2005. The literature search was re-run in August 2006 and March 2007. SELECTION CRITERIA: Randomised controlled trials (RCTs) in patients with inoperable or unresectable primary oesophageal cancer who underwent palliative treatment. We included rigid plastic intubation, self-expanding metallic stent (SEMS) insertion, brachytherapy, external beam radiotherapy, chemotherapy, oesophageal bypass surgery, chemical and thermal ablation therapy, either head-to-head or in combination. The primary outcome was dysphagia improvement. Secondary outcomes included recurrent dysphagia, technical success, procedure related mortality, 30-day mortality, adverse effects and quality of life. DATA COLLECTION AND ANALYSIS: One author assessed the eligibility criteria of each study and extracted data regarding outcomes and factors affecting risk of bias. MAIN RESULTS: We included 2542 patients from 40 studies. SEMS insertion is safer and more effective than plastic tube insertion. Thermal and chemical ablative therapy provide comparable dysphagia palliation but have an increased requirement for re-interventions and adverse effects. Anti-reflux stents provide comparable dysphagia palliation to conventional metal stents. Some anti-reflux stents might reduce gastro-oesophageal reflux compared to conventional metal stents. Brachytherapy might be a suitable alternative to SEMS in providing a survival advantage and possibly a better quality of life. AUTHORS' CONCLUSIONS: Self-expanding metal stent insertion is safe, effective and quicker in palliating dysphagia compared to other modalities. However, high-dose intraluminal brachytherapy is a suitable alternative and might provide additional survival benefit with a better quality of life. Self-expanding metal stent insertion and brachytherapy provide comparable palliation to endoscopic ablative therapy but are preferable due to the reduced requirement for re-interventions. Rigid plastic tube insertion, dilatation alone or in combination with other modalities, chemotherapy alone, combination chemoradiotherapy and bypass surgery are not recommended for palliation of dysphagia due to a high incidence of delayed complications and recurrent dysphagia.

30 day mortality in adult palliative radiotherapy--A retrospective population based study of 14,972 treatment episodes.

BACKGROUND: 30-day mortality (30DM) has been suggested as a clinical indicator of the avoidance of harm in palliative radiotherapy within the NHS, but no large-scale population-based studies exist. This large retrospective cohort study aims to investigate the factors that influence 30DM following palliative radiotherapy and consider its value as a clinical indicator. METHODS: All radiotherapy episodes delivered in a large UK cancer centre between January 2004 and April 2011 were analysed. Patterns of palliative radiotherapy, 30DM and the variables affecting 30DM were assessed. The impact of these variables was assessed using logistic regression. RESULTS: 14,972 palliative episodes were analysed. 6334 (42.3%) treatments were delivered to bone metastases, 2356 (15 7%) to the chest for lung cancer and 915 (5.7%) to the brain. Median treatment time was 1day (IQR 1-7). Overall 30DM was 12.3%. Factors having a significant impact upon 30DM were sex, primary diagnosis, treatment site and fractionation schedule (p<0.01). CONCLUSION: This is the first large-scale description of 30-day mortality for unselected adult palliative radiotherapy treatments. The observed differences in early mortality by fractionation support the use of this measure in assessing clinical decision making in palliative radiotherapy and require further study in other centres and health care systems.

The role of endoscopic ultrasound (EUS) in planning radiotherapy target volumes for oesophageal cancer.

Computed tomography (CT) scanning is the main imaging modality utilised for planning radical oesophageal radiotherapy. Endoscopic ultrasound allows accurate localisation and local staging of oesophageal tumours. A method of incorporating this information into the CT planning process is described. Gross tumour volume position changes that occur when using this technique are presented.

A phase I and pharmacokinetic study of capecitabine in combination with radiotherapy in patients with localised inoperable pancreatic cancer.

PURPOSE: The purpose of this phase I study was to determine the safety, toxicity, maximum tolerated dose, and pharmacokinetics of capecitabine when administered concurrently with radiotherapy in patients with localised, inoperable pancreatic adenocarcinoma. METHODS: Eligible patients, with adequate performance status and organ function, were treated in escalating dose cohorts with capecitabine, administered 7 days a week, twice daily, and radiotherapy (50.4 Gy in 28 fractions over 38 days). Cohorts of six patients were treated at four planned dose levels. Pharmacokinetic (PK) studies were undertaken on day 1 of treatment. RESULTS: Twenty-five patients, performance status ECOG ≤2, were recruited to the study. Dose-limiting toxicities were grade 3 vomiting (1 patient) and grade 3 fatigue (1 patient), both at 1,000 mg/m². The recommended phase II dose was 825 mg/m². No grade 3/4 haematological toxicities were observed. PK studies did not suggest any effect of pancreatic malignancy or concurrent radiotherapy on the PK parameters of capecitabine and its metabolites. CONCLUSION: Capecitabine-based chemo-radiotherapy, using a twice daily dosing schedule of 825 mg/m² given 7 days per week concurrently with 50.4 Gy external beam radiotherapy, is well tolerated in patients with locally advanced pancreatic cancer.

Phase II Trial of Cetuximab and Conformal Radiotherapy Only in Locally Advanced Pancreatic Cancer with Concurrent Tissue Sampling Feasibility Study.

BACKGROUND: Preclinical data have indicated the anti-epidermal growth factor receptor (EGFR) agent cetuximab (Erbitux) as a radiosensitizer in pancreatic cancer, but this has not been specifically addressed in a clinical study. We report the results of an original study initiated in 2007, where cetuximab was tested with radiotherapy (RT) alone in locally advanced pancreatic cancer in a phase II trial (PACER). METHODS: Patients (n = 21) received cetuximab loading dose (400 mg/m(2)) and weekly dose (250 mg/m(2)) during RT (50.4 Gy in 28 fractions). Toxicity and disease response end point data were prospectively assessed. A feasibility study of on-trial patient blood and skin sampling was incorporated. RESULTS: Treatment was well tolerated, and toxicity was low; most patients (71%) experienced acute toxicities of grade 2 or less. Six months posttreatment, stable local disease was achieved in 90% of evaluable patients, but only 33% were free from metastatic progression. Median overall survival was 7.5 months, and actuarial survival was 33% at 1 year and 11% at 3 years, reflecting swift metastatic progression in some patients but good long-term control of localized disease in others. High-grade acneiform rash (P = .0027), posttreatment stable disease (P = .0059), and pretreatment cancer antigen 19.9 (CA19.9) level (P = .0042) associated with extended survival. Patient skin and blood samples yielded sufficient RNA and good quality protein, respectively. CONCLUSIONS: The results indicate that cetuximab inhibits EGFR-mediated radioresistance to achieve excellent local control with minimal toxicity but does not sufficiently control metastatic progression in all patients. Translational studies of patient tissue samples may yield molecular information that may enable individual treatment response prediction.

Short-course radiotherapy, with elective delay prior to surgery, in patients with unresectable rectal cancer who have poor performance status or significant co-morbidity.

BACKGROUND AND PURPOSE: Standard treatment for rectal cancer which threatens the expected plane of resection on MRI imaging is long-course, pre-operative chemoradiotherapy (1.8-2Gy, 25-28 fractions). Not all patients are suitable for this because of age, poor performance status or co-morbidities. We describe our experience of short-course (5x5Gy) pre-operative radiotherapy with planned, delayed surgery (SCPRT-delay) in this patient group. MATERIALS AND METHODS: Between April 2001 and October 2007, 43 patients were selected for SCPRT-delay. The clinical records were retrospectively evaluated. RESULTS: Median age was 82 (range 58-87). Forty-one patients had radiotherapy of which 26 (61%) were subsequently able to have surgery. Of these, R0, R1 and R2 resections were performed in 22, 2 and 2 patients, respectively. Treatment was well tolerated, although two patients required hospital admission for management of diarrhoea and one developed significant late small bowel toxicity, attributable to radiotherapy. In those undergoing R0 or R1 resection there have been no local recurrences (median follow-up 18 months). Median survival for the whole group was 23 months, although this was 44 months in those undergoing surgery. CONCLUSIONS: SCPRT-delay appears to be a useful alternative to long-course pre-operative chemoradiotherapy in this high-risk group of patients.

Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer.

PURPOSE: Both gemcitabine (GEM) and fluoropyrimidines are valuable treatment for advanced pancreatic cancer. This open-label study was designed to compare the overall survival (OS) of patients randomly assigned to GEM alone or GEM plus capecitabine (GEM-CAP). PATIENTS AND METHODS: Patients with previously untreated histologically or cytologically proven locally advanced or metastatic carcinoma of the pancreas with a performance status