Training in Radiation and Clinical Oncology in Europe.

The European population is strongly affected by cancer. Radiotherapy is roughly used in 50% of cancer patients in European countries. The increased cancer burden demands a new generation of radiation/clinical oncologist (RO/CO) that, besides a strong evidence-based oncological knowledge, will be ready for leadership in cancer care. The mutual recognition of professional qualifications of Radiation/Clinical Oncology in the EU needs training harmonization. The European Society of Radiotherapy and Oncology (ESTRO) and the European Union for Medical Specialties (UEMS) made important efforts toward a European Common Curriculum for RO/CO leadership in cancer care. If qualifications are mutually recognized, the training supporting these qualifications should be also harmonized. Since 1991, ESTRO produced several editions of the Core Curriculum in Radiation Oncology (1991, 2004, 2012, 2019). These Core Curricula were endorsed as European Training Requirements by the UEMS in 2004, 2013, and 2019. A core curriculum for clinical oncology was also produced to provide this harmonization tool to countries where radiation oncology is practiced inside the broader specialty of clinical oncology. New initiatives are in place to continuously adapt the training programs to the rapidly evolving cancer care organization.

An inter-specialty cancer training programme curriculum for Europe.

INTRODUCTION: Multidisciplinary and multi-professional collaboration is vital in providing better outcomes for patients The aim of the INTERACT-EUROPE Project (Wide Ranging Cooperation and Cutting Edge Innovation As A Response To Cancer Training Needs) was to develop an inter-specialty curriculum. A pilot project will enable a pioneer cohort to acquire a sample of the competencies needed. METHODS: A scoping review, qualitative and quantitative surveys were undertaken. The quantitative survey results are reported here. Respondents, including members of education boards, curriculum committees, trainee committees of European specialist societies and the ECO Patient Advisory Committee, were asked to score 127 proposed competencies on a 7-point Likert scale as to their value in achieving the aims of the curriculum. Results were discussed and competencies developed at two stakeholder meetings. A consultative document, shared with stakeholders and available online, requested views regarding the other components of the curriculum. RESULTS: Eleven competencies were revised, three omitted and three added. The competencies were organised according to the CanMEDS framework with 13 Entrustable Professional Activities, 23 competencies and 127 enabling competencies covering all roles in the framework. Recommendations regarding the infrastructure, organisational aspects, eligibility of trainees and training centres, programme contents, assessment and evaluation were developed using the replies to the consultative document. CONCLUSIONS: An Inter-specialty Cancer Training Programme Curriculum and a pilot programme with virtual and face-to-face components have been developed with the aim of improving the care of people affected by cancer.

Brachytherapy training survey among radiation oncology residents in Europe.

We aim to investigate the current state of brachytherapy (BT) training among the radiation oncology trainees in Europe. MATERIAL AND METHODS: A 22-question online survey based on the one by the American Association of Radiation Oncology Residents (2017) with added queries pertinent to training in Europe was sent to 1450 residents in two iterations. These included site-specific training, volume of experience, barriers to training, institutional support, and preferences for further education. Responses to individual statements were given on a 1 to 5 Likert-type scale. The answers were reported by junior (≤3 years of training) and senior years of training (year of training 4/5/6 and junior staff). Descriptive statistics were used to describe frequencies. RESULTS: Residents from 21 European countries participated, 445 (31%) responded. 205 (47%) were senior residents. 60% residents consider that performing BT independently at the end of residency is very or somewhat important. Confidence in joining a brachytherapy practice at the end of residency was high or somewhat high in 34% of senior residents. They reported as barriers to achieving independence in BT to be lack of appropriate didactic/procedural training from supervisors (47%) and decreased case load (31%). 68% reported their program lacks a formal BT curriculum and standardized training assessment. CONCLUSIONS: Residents in Europe, feel independent BT practice is very or somewhat important, but do not feel confident they will achieve this goal. To address this gap, efforts are needed to develop and implement a formal and comprehensive BT curriculum with easy access to trained instructors.

A new wave of leaders: Early evaluation of the interdisciplinary Foundations of Leadership in Radiation Oncology (FLiRO) program.

Purpose: Effective leadership across all areas of radiation oncology (RO) is vital to fully realise the benefits of radiation therapy in cancer care. We report outcomes of a novel interdisciplinary leadership program designed for RO professionals under a global joint society initiative. Methods: The Foundations of Leadership in RO (FLiRO) program was designed for aspiring RO leaders. Initially delivered in a blended learning format, it was adapted to fully virtual in 2021. It comprised a webinar tutorial, on-line modules and homework followed by 'live' in-person/virtual workshops over an approximately 6-week period. Topics included personal awareness, effective teamwork, quality improvement skills, leading change and conflict management. An immediate post-program online survey was performed using Likert scales to measure self-reported educational value, interaction with others and the likely application of learning to practice. Open comments were invited. Results: 170 participants from 36 countries and 6 continents took part from 2018 to 2021 (99 doctors, 36 physicists, 32 radiation therapists/RTTs and 3 others). 141 (83%) participants responded to the post-program survey. Average weightings for responders' views on whether pre-determined learning objectives were met ranged from 4.30 to 4.61 on a 5-point scale (1 = 'not met at all' and 5 = completely met). For the question addressing potential value of learning for application to their workplace, 124 of 130 (95%) of responders indicated that FLIRO would be 'very useful' or 'extremely useful'. Conclusion: Initial evaluation of the FLiRO program supports its continuation and expansion with ongoing evolution based on emerging evidence around leadership education and participant feedback.

The ESSO core curriculum committee update on surgical oncology.

INTRODUCTION: Surgical oncology is a defined specialty within the European Board of Surgery within the European Union of Medical Specialists (UEMS). Variation in training and specialization still occurs across Europe. There is a need to align the core knowledge needed to fulfil the criteria across subspecialities in surgical oncology. MATERIAL AND METHODS: The core curriculum, established in 2013, was developed with contributions from expert advisors from within the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy and Oncology (ESTRO) and European Society of Medical Oncology (ESMO) and related subspeciality experts. RESULTS: The current version reiterates and updates the core curriculum structure needed for current and future candidates who plans to train for and eventually sit the European fellowship exam for the European Board of Surgery in Surgical Oncology. The content included is not intended to be exhaustive but, rather to give the candidate an idea of expectations and areas for in depth study, in addition to the practical requirements. The five elements included are: Basic principles of oncology; Disease site specific oncology; Generic clinical skills; Training recommendations, and, lastly; Eligibility for the EBSQ exam in Surgical Oncology. CONCLUSIONS: As evidence-based care for cancer patients evolves through research into basic science, translational research and clinical trials, the core curriculum will evolve, mature and adapt to deliver continual improvements in cancer outcomes for patients.

Evaluation of multiple transcriptomic gene risk signatures in male breast cancer.

Male breast cancer (BCa) is a rare disease accounting for less than 1% of all breast cancers and 1% of all cancers in males. The clinical management is largely extrapolated from female BCa. Several multigene assays are increasingly used to guide clinical treatment decisions in female BCa, however, there are limited data on the utility of these tests in male BCa. Here we present the gene expression results of 381 M0, ER+ve, HER2-ve male BCa patients enrolled in the Part 1 (retrospective analysis) of the International Male Breast Cancer Program. Using a custom NanoString™ panel comprised of the genes from the commercial risk tests Prosigna®, OncotypeDX®, and MammaPrint®, risk scores and intrinsic subtyping data were generated to recapitulate the commercial tests as described by us previously. We also examined the prognostic value of other risk scores such as the Genomic Grade Index (GGI), IHC4-mRNA and our prognostic 95-gene signature. In this sample set of male BCa, we demonstrated prognostic utility on univariate analysis. Across all signatures, patients whose samples were identified as low-risk experienced better outcomes than intermediate-risk, with those classed as high risk experiencing the poorest outcomes. As seen with female BCa, the concordance between tests was poor, with C-index values ranging from 40.3% to 78.2% and Kappa values ranging from 0.17 to 0.58. To our knowledge, this is the largest study of male breast cancers assayed to generate risk scores of the current commercial and academic risk tests demonstrating comparable clinical utility to female BCa.

Clinical oncology module for the ESTRO core curriculum.

INTRODUCTION: Clinical oncologists are physicians with the competencies to manage cancer patients through the entire disease pathway combining the competencies of radiation and medical oncologists. The 4th edition of the European Society for Radiotherapy and Oncology Core Curriculum for Radiation Oncology/Radiotherapy (ESTRO curriculum) has received wide support by the clinical oncology community. The aim was to develop a clinical oncology module that could be combined with the ESTRO curriculum to enable clinical oncology trainees to follow a single curriculum. MATERIALS AND METHODS: A range of stakeholders including National Society representatives, an oncologist from a low- middle-income country, and a recently appointed specialist, developed and commented on iterations of the curriculum. Further modifications were made by the ESTRO Education Council. RESULTS: The module is based on the CanMEDS 2015 framework and identifies 20 enabling competencies in the Medical Expert role that are required in addition to the ESTRO curriculum for the training of clinical oncologists. Recommendations are made for the levels of Entrustable Professional Activities (EPAs) to be attained by the end of training. CONCLUSIONS: The Clinical Oncology module, when combined with the ESTRO curriculum, covers the entire cancer pathway rather than being modality specific. It is hoped it will aid in the development of comparable standards of training in clinical oncology across Europe and may also have utility in low- and middle-income countries as well as providing a single curriculum for trainees.

Exploring implementation of the ESTRO Core Curriculum at the national level.

BACKGROUND AND PURPOSE: Global curricula exist across medical specialties however, the factors which influence their implementation are not well understood. The purpose of this study is to report the perceived factors that impact the implementation of the ESTRO Core Curriculum. METHODS: An anonymous, 37-item, survey was designed and distributed to the Presidents of the National Societies who have endorsed the ESTRO Core Curriculum (n = 29). The survey addressed perceptions about implementation factors related to context, process and curriculum change. The data was summarized using descriptive statistics. RESULTS: Twenty-six (90%) National Societies completed the survey. One respondent perceived that the values of the training system of their country would be incompatible with the proposed ESTRO Core Curriculum. The most common contextual barriers to implementation was a lack of support from the government (57%), a lack of internal organizational support (35%) and a 'poor fit' between the ESTRO Core Curriculum and the broader political and economic context (35%). Perceived implementation process barriers included insufficient numbers of faculty (44%), poor coordination between the government and training institutions (48%), and a lack of an influential person leading the implementation (44%). Two barriers related to curriculum change were a lack of funding and lack of assessment tools. CONCLUSIONS: The content and values espoused in the ESTRO Core Curriculum are endorsed across diverse geopolitical and sociocultural regions. Barriers to curricular implementation are identified at the organizational and systems level and include insufficient teaching faculty, lack of coordination and the need for influential leadership.

Recommended ESTRO Core Curriculum for Radiation Oncology/Radiotherapy 4th edition.

INTRODUCTION: In 2017 it was decided to revise the European Core Curriculum for Radiation Oncology/Radiotherapy to produce a 4th edition. The aims of the ESTRO curriculum are to develop comparable standards for training across Europe and to facilitate free movement of specialists across borders. It is also hoped that it will improve the level of training across Europe and will make the non-medical expert roles more explicit. MATERIALS AND METHODS: A wide range of stakeholders including National Society representatives, trainees, recently appointed specialists, members of the European Union Medical Specialists Radiotherapy section, an RTT, a radiobiologist, a physicist and lay members from ESTRO staff developed and commented on iterations of the curriculum. RESULTS: The 4th edition is based on the CanMEDS 2015 framework and identifies 14 Entrustable Professional Activities (EPAs) and the competencies required to perform these. The manager role is replaced by competencies related to leadership. The levels of proficiency required for tumour sites is defined as levels of EPAs. CONCLUSIONS: It is hoped that the inclusive method of developing the 4th edition has resulted in a document that will have utility in the wide range of environments in which radiation oncology is practised in Europe.

CHOP versus GEM-P in previously untreated patients with peripheral T-cell lymphoma (CHEMO-T): a phase 2, multicentre, randomised, open-label trial.

BACKGROUND: Outcomes with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) or CHOP-like chemotherapy in peripheral T-cell lymphoma are poor. We investigated whether the regimen of gemcitabine, cisplatin, and methylprednisolone (GEM-P) was superior to CHOP as front-line therapy in previously untreated patients. METHODS: We did a phase 2, parallel-group, multicentre, open-label randomised trial in 47 hospitals: 46 in the UK and one in Australia. Participants were patients aged 18 years and older with bulky (tumour mass diameter >10 cm) stage I to stage IV disease (WHO performance status 0-3), previously untreated peripheral T-cell lymphoma not otherwise specified, angioimmunoblastic T-cell lymphoma, anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, enteropathy-associated T-cell lymphoma, or hepatosplenic γδ T-cell lymphoma. We randomly assigned patients (1:1) stratified by subtype of peripheral T-cell lymphoma and international prognostic index to either CHOP (intravenous cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1·4 mg/m2 [maximum 2 mg] on day 1, and oral prednisolone 100 mg on days 1-5) every 21 days for six cycles; or GEM-P (intravenous gemcitabine 1000 mg/m2 on days 1, 8, and 15, cisplatin 100 mg/m2 on day 15, and oral or intravenous methylprednisolone 1000 mg on days 1-5) every 28 days for four cycles. The primary endpoint was the proportion of patients with a CT-based complete response or unconfirmed complete response on completion of study chemotherapy, to detect a 20% superiority of GEM-P compared with CHOP, assessed in all patients who received at least one cycle of treatment and had an end-of-treatment CT scan or reported clinical progression as the reason for stopping trial treatment. Safety was assessed in all patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov (NCT01719835) and the European Clinical Trials Database (EudraCT 2011-004146-18). FINDINGS: Between June 18, 2012, and Nov 16, 2016, we randomly assigned 87 patients to treatment, 43 to CHOP and 44 to GEM-P. A planned unmasked review of efficacy data by the independent data monitoring committee in November, 2016, showed that the number of patients with a confirmed or unconfirmed complete response with GEM-P was non-significantly inferior compared with CHOP and the trial was closed early. At a median follow-up of 27·4 months (IQR 16·6-38·4), 23 patients (62%) of 37 assessable patients assigned to CHOP had achieved a complete response or unconfirmed complete response compared with 17 (46%) of 37 assigned to GEM-P (odds ratio 0·52, 95% CI 0·21-1·31; p=0·164). The most common adverse events of grade 3 or worse in both groups were neutropenia (17 [40%] with CHOP and nine [20%] with GEM-P), thrombocytopenia (4 [10%] with CHOP and 13 [30%] with GEM-P, and febrile neutropenia (12 [29%] with CHOP and 3 [7%] with GEM-P). Two patients (5%) died during the study, both in the GEM-P group, from lung infections. INTERPRETATION: The number of patients with a complete response or unconfirmed complete response did not differ between the groups, indicating that GEM-P was not superior for this outcome. CHOP should therefore remain the reference regimen for previously untreated peripheral T-cell lymphoma. FUNDING: Bloodwise and the UK National Institute of Health Research.

Multidisciplinary training of cancer specialists in Europe.

The best care for patients with cancer is most likely to be achieved when decisions about diagnosis, staging and treatment are made at multidisciplinary and multiprofessional meetings, preferably when all the professional expertise relevant to the patient's condition is gathered together. Questionnaires were sent to National Societies of Radiation Oncology and Medical Oncology concerning similarities and differences in training programs and multidisciplinary care in member states in Europe. Results indicated wide variation in training systems and practice. Data were lacking for Surgery because Surgical Oncology is not recognised as a speciality in the EU and most specialist training in cancer surgery is organ based. A period of time in cross-disciplinary training in each of the other two disciplines for all trainees in Medical Oncology, Radiation Oncology and Surgical Oncology (including all surgeons training in cancer surgery) is recommended. This is likely to improve the value of multidisciplinary meetings and may result in improved patient care. The Expert Group on Cancer Control of the European Commission has endorsed this recommendation.

Defining a Leader Role curriculum for radiation oncology: A global Delphi consensus study.

BACKGROUND AND PURPOSE: The need for radiation oncologists and other radiation oncology (RO) professionals to lead quality improvement activities and contribute to shaping the future of our specialty is self-evident. Leadership knowledge, skills and behaviours, like other competencies, can be learned (Blumenthal et al., 2012). The objective of this study was to define a globally applicable competency set specific to radiation oncology for the CanMEDS Leader Role (Frank et al., 2015). METHODS: A modified Delphi consensus process delivering two rounds of on-line surveys was used. Participants included trainees, radiation/clinical oncologists and other RO team members (radiation therapists, physicists, and nurses), professional educators and patients. RESULTS: 72 of 95 (76%) invitees from nine countries completed the Round 1 (R1) survey. Of the 72 respondents to RI, 70 completed Round 2 (R2) (97%). In R1, 35 items were deemed for 'inclusion' and 21 for 'exclusion', leaving 41 'undetermined'. After review of items, informed by participant comments, 14 competencies from the 'inclusion' group went into the final curriculum; 12 from the 'undetermined' group went to R2. In R2, 6 items reached consensus for inclusion. CONCLUSION: This process resulted in 20 RO Leader Role competencies with apparent global applicability. This is the first step towards developing learning, teaching and assessment tools for this important area of training.

Pathological characterisation of male breast cancer: Results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program.

AIM: Several prognostic histological features have been established in female breast cancer (BC), but it is unknown whether these can be extrapolated to male BC patients. The aim of this study was to evaluate the prognostic value of several histological features in a large series of male BC. METHODS: Central pathology review was performed for 1483 male BCs collected through part 1 of the European Organisation for Research and Treatment of Cancer (EORTC) International Male BC Program. Pathology review included histological subtype, grade, mitotic activity index (MAI), presence of a fibrotic focus and density of tumour-infiltrating lymphocytes (TILs). These features were correlated with clinical outcome. The relationship between these features and surrogate molecular subtypes using immunohistochemistry was also assessed. RESULTS: Median follow-up for overall survival (OS) was 7.1 years. Overall histological grade was not significantly associated with OS (p = 0.129). MAI, the presence of a fibrotic focus and a low TIL density however were correlated with unfavourable OS (p = 0.023, p = 0.004 and p = 0.011, respectively). BC subtype correlated with TIL density (p = 0.015), as we observed a higher density for human epidermal growth factor receptor type 2 (HER2) positive BC compared to luminal HER2-negative subtype. No association was observed between subtype and fibrotic focus. CONCLUSIONS: Histologic grade was not significantly correlated with clinical outcome in this series, unlike what is seen in female patients. These results contribute to our understanding of male BC and indicate the importance of further research on the optimisation of risk stratification and treatment decisions for male BC patients.

Best time to assess complete clinical response after chemoradiotherapy in squamous cell carcinoma of the anus (ACT II): a post-hoc analysis of randomised controlled phase 3 trial.

BACKGROUND: Guidelines for anal cancer recommend assessment of response at 6-12 weeks after starting treatment. Using data from the ACT II trial, we determined the optimum timepoint to assess clinical tumour response after chemoradiotherapy. METHODS: The previously reported ACT II trial was a phase 3 randomised trial of patients of any age with newly diagnosed, histologically confirmed, squamous cell carcinoma of the anus without metastatic disease from 59 centres in the UK. We randomly assigned patients (by minimisation) to receive either intravenous mitomycin (one dose of 12 mg/m2 on day 1) or intravenous cisplatin (one dose of 60 mg/m2 on days 1 and 29), with intravenous fluorouracil (one dose of 1000 mg/m2 per day on days 1-4 and 29-32) and radiotherapy (50·4 Gy in 28 daily fractions); and also did a second randomisation after initial therapy to maintenance chemotherapy (fluorouracil and cisplatin) or no maintenance chemotherapy. The primary outcome was complete clinical response (the absence of primary and nodal tumour by clinical examination), in addition to overall survival and progression-free survival from time of randomisation. In this post-hoc analysis, we analysed complete clinical response at three timepoints: 11 weeks from the start of chemoradiotherapy (assessment 1), 18 weeks from the start of chemoradiotherapy (assessment 2), and 26 weeks from the start of chemoradiotherapy (assessment 3) as well as the overall and progression-free survival estimates of patients with complete clinical response or without complete clinical response at each assessment. We analysed both the overall trial population and a subgroup of patients who had attended each of the three assessments by modified intention-to-treat. This study is registered at controlled-trials.com, ISRCTN 26715889. FINDINGS: We enrolled 940 patients from June 4, 2001, until Dec 16, 2008. Complete clinical response was achieved in 492 (52%) of 940 patients at assessment 1 (11 weeks), 665 (71%) of patients at assessment 2 (18 weeks), and 730 (78%) of patients at assessment 3 (26 weeks). 691 patients attended all three assessments and in this subgroup, complete clinical response was reported in 441 (64%) patients at assessment 1, 556 (80%) at assessment 2, and 590 (85%) at assessments 3. 151 (72%) of the 209 patients who had not had a complete clinical response at assessment 1 had a complete clinical response by assessment 3. In the overall trial population of 940 patients, 5 year overall survival in patients who had a clinical response at assessments 1, 2, 3 was 83% (95% CI 79-86), 84% (81-87), and 87% (84-89), respectively and was 72% (66-78), 59% (49-67), and 46% (37-55) for patients who did not have a complete clinical response at assessments 1, 2, 3, respectively. In the subgroup of 691 patients, 5 year overall survival in patients who had a clinical response at assessment 1, 2, 3 was 85% (81-88), 86% (82-88), and 87% (84-90), respectively, and was 75% (68-80), 61% (50-70), and 48% (36-58) for patients who did not have a complete clinical response at assessment 1, 2, 3, respectively. Similarly, progression-free survival in both the overall trial population and the subgroup was longer in patients who had a complete clinical response, compared with patients who did not have a complete clinical response, at all three assessments. INTERPRETATION: Many patients who do not have a complete clinical response when assessed at 11 weeks after commencing chemoradiotherapy do in fact respond by 26 weeks, and the earlier assessment could lead to some patients having unnecessary surgery. Our data suggests that the optimum time for assessment of complete clinical response after chemoradiotherapy for patients with squamous cell carcinoma of the anus is 26 weeks from starting chemoradiotherapy. We suggest that guidelines should be revised to indicate that later assessment is acceptable. FUNDING: Cancer Research UK.

Male breast cancer precursor lesions: analysis of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program.

In men, data regarding breast cancer carcinogenesis are limited. The aim of our study was to describe the presence of precursor lesions adjacent to invasive male breast cancer, in order to increase our understanding of carcinogenesis in these patients. Central pathology review was performed for 1328 male breast cancer patients, registered in the retrospective joint analysis of the International Male Breast Cancer Program, which included the presence and type of breast cancer precursor lesions. In a subset, invasive breast cancer was compared with the adjacent precursor lesion by immunohistochemistry (n=83) or targeted next generation sequencing (n=7). Additionally, we correlated the presence of ductal carcinoma in situ with outcome. A substantial proportion (46.2%) of patients with invasive breast cancer also had an adjacent precursor lesion, mainly ductal carcinoma in situ (97.9%). The presence of lobular carcinoma in situ and columnar cell-like lesions were very low (<1%). In the subset of invasive breast cancer cases with adjacent ductal carcinoma in situ (n=83), a complete concordance was observed between the estrogen receptor, progesterone receptor, and HER2 status of both components. Next generation sequencing on a subset of cases with invasive breast cancer and adjacent ductal carcinoma in situ (n=4) showed identical genomic aberrations, including PIK3CA, GATA3, TP53, and MAP2K4 mutations. Next generation sequencing on a subset of cases with invasive breast cancer and an adjacent columnar cell-like lesion showed genomic concordance in two out of three patients. A multivariate Cox model for survival showed a trend that the presence of ductal carcinoma in situ was associated with a better overall survival, in particular in the Luminal B HER2+ subgroup. In conclusion, ductal carcinoma in situ is the most commonly observed precursor lesion in male breast cancer and its presence seems to be associated with a better outcome, in particular in Luminal B HER2+ cases. The rate of lobular carcinoma in situ and columnar cell-like lesions adjacent to male breast cancer is very low, but our findings support the role of columnar cell-like lesions as a precursor of male breast cancer.

Perspectives on medical education in radiation oncology and the role of the ESTRO School.

Radiation oncology is a medical specialty not just delivering ionizing radiation to cancer patients but also participating as an important partner in the care of the patient from diagnosis to cure, follow up or end of life. The specialty is rapidly evolving in a multi- and interdisciplinary setting as multimodality treatment is becoming frequent. This requires that the medical undergraduate and postgraduate training evolve to these changes. The ESTRO School has for more than 30 years offered postgraduate training courses in and outside Europe and strives to develop its services to accommodate the educational needs of a specialty in constant development. Some of these developments are described in the present paper.

Establishing a Global Radiation Oncology Collaboration in Education (GRaCE): Objectives and priorities.

Representatives from countries and regions world-wide who have implemented modern competency-based radiation- or clinical oncology curricula for training medical specialists, met to determine the feasibility and value of an ongoing international collaboration. In this forum, educational leaders from the ESTRO School, encompassing many European countries adopting the ESTRO Core Curriculum, and clinician educators from Canada, Denmark, the United Kingdom, Australia and New Zealand considered the training and educational arrangements within their jurisdictions, identifying similarities and challenges between programs. Common areas of educational interest and need were defined, which included development of new competency statements and assessment tools, and the application of the latter. The group concluded that such an international cooperation, which might expand to include others with similar goals, would provide a valuable vehicle to ensure training program currency, through sharing of resources and expertise, and enhance high quality radiation oncology education. Potential projects for the Global Radiation Oncology Collaboration in Education (GRaCE) were agreed upon, as was a strategy designed to maintain momentum. This paper describes the rationale for establishing this collaboration, presents a comparative view of training in the jurisdictions represented, and reports early goals and priorities.

Panitumumab and irinotecan versus irinotecan alone for patients with KRAS wild-type, fluorouracil-resistant advanced colorectal cancer (PICCOLO): a prospectively stratified randomised trial.

BACKGROUND: Therapeutic antibodies targeting EGFR have activity in advanced colorectal cancer, but results from clinical trials are inconsistent and the population in which most benefit is derived is uncertain. Our aim was to assess the addition of panitumumab to irinotecan in pretreated advanced colorectal cancer. METHODS: In this open-label, randomised trial, we enrolled patients who had advanced colorectal cancer progressing after fluoropyrimidine treatment with or without oxaliplatin from 60 centres in the UK. From December, 2006 until June, 2008, molecularly unselected patients were recruited to a three-arm design including irinotecan (control), irinotecan plus ciclosporin, and irinotecan plus panitumumab (IrPan) groups. From June 10, 2008, in response to new data, the trial was amended to a prospectively stratified design, restricting panitumumab randomisation to patients with KRAS wild-type tumours; the results of the comparison between the irinotcan and IrPan groups are reported here. We used a computer-generated randomisation sequence (stratified by previous EGFR targeted therapy and then minimised by centre, WHO performance status, previous oxaliplatin, previous bevacizumab, previous dose modifications, and best previous response) to randomly allocate patients to either irinotecan or IrPan. Patients in both groups received 350 mg/m(2) intravenous irinotecan every 3 weeks (300 mg/m(2) if aged ≥70 years or a performance status of 2); patients in the IrPan group also received intravenous panitumumab 9 mg/kg every 3 weeks. The primary endpoint was overall survival in KRAS wild-type patients who had not received previous EGFR targeted therapy, analysed by intention to treat. Tumour DNA was pyrosequenced for KRASc.146, BRAF, NRAS, and PIK3CA mutations, and predefined molecular subgroups were analysed for interaction with the effect of panitumumab. This study is registered, number ISRCTN93248876. RESULTS: Between Dec 4, 2006, and Aug 31, 2010, 1198 patients were enrolled, of whom 460 were included in the primary population of patients with KRASc.12-13,61 wild-type tumours and no previous EGFR targeted therapy. 230 patients were randomly allocated to irinotecan and 230 to IrPan. There was no difference in overall survival between groups (HR 1·01, 95% CI 0·83-1·23; p=0·91), but individuals in the IrPan group had longer progression-free survival (0·78, 0·64-0·95; p=0·015) and a greater number of responses (79 [34%] patients vs 27 [12%]; p<0·0001) than did individuals in the irinotecan group. Grade 3 or worse diarrhoea (64 [29%] of 219 patients vs 39 [18%] of 218 patients), skin toxicity (41 [19%] vs none), lethargy (45 [21]% vs 24 [11%]), infection (42 [19%] vs 22 [10%]) and haematological toxicity (48 [22%] vs 27 [12%]) were reported more commonly in the IrPan group than in the irinotecan group. We recorded five treatment-related deaths, two in the IrPan group and three in the irinotecan group. INTERPRETATION: Adding panitumumab to irinotecan did not improve the overall survival of patients with wild-type KRAS tumours. Further refinement of molecular selection is needed for substantial benefits to be derived from EGFR targeting agents. FUNDING: Cancer Research UK, Amgen Inc.