Safety and preliminary activity results of the GATTO study, a phase Ib study combining the anti-TA-MUC1 antibody gatipotuzumab with the anti-EGFR tomuzotuximab in patients with refractory solid tumors.

BACKGROUND: The phase I GATTO study (NCT03360734) explored the feasibility, tolerability and preliminary activity of combining gatipotuzumab, a novel humanized monoclonal antibody binding to the tumor-associated epitope of mucin 1 (TA-MUC1) and an anti-epidermal growth factor receptor (anti-EGFR) antibody in refractory solid tumors. PATIENTS AND METHODS: Initially the study enrolled primary phase (PP) patients with EGFR-positive metastatic solid tumors, for whom no standard treatment was available. Patients received gatipotuzumab administered at 1400 mg every 2 weeks, 6 weeks after the start of the glyco-optimized anti-EGFR antibody tomuzotuximab at 1200 mg every 2 weeks. As this regimen was proven safe, enrollment continued in an expansion phase (EP) of patients with refractory metastatic colorectal cancer, non-small-cell lung cancer, head and neck cancer and breast cancer. Tomuzotuximab and gatipotuzumab were given at the same doses and gatipotuzumab treatment started 1 week after the first dose of the anti-EGFR antibody. Additionally, investigators could use a commercial anti-EGFR antibody in place of tomuzotuximab. RESULTS: A total of 52 patients were enrolled, 20 in the PP and 32 in the EP. The combined treatment was well tolerated and no dose-limiting toxicity was observed in the whole study, nor related serious adverse event or death. Preliminary activity of the combination was observed, with one and four RECIST partial responses in the PP and EP, all in colorectal cancer patients. The trial was accompanied by a comprehensive translational research program for identification of biomarkers, including soluble TA-MUC1 (sTA-MUC1) in serum. In the EP, patients with baseline sTA-MUC1 levels above the median appeared to have improved progression-free survival and overall survival. CONCLUSIONS: Combination of a TA-MUC1-targeting antibody and an EGFR-targeting antibody is safe and feasible. Interesting antitumor activity was observed in heavily pretreated patients. Future studies should test this combination together with chemotherapy and explore the potential of sTA-MUC1 as a companion biomarker for further development of the combination.

Maintenance therapy of patients with recurrent epithelial ovarian carcinoma with the anti-tumor-associated-mucin-1 antibody gatipotuzumab: results from a double-blind, placebo-controlled, randomized, phase II study.

BACKGROUND: Gatipotuzumab is a humanized monoclonal antibody recognizing the carbohydrate-induced epitope of the tumor-associated mucin-1 (TA-MUC1). This study aimed to evaluate the efficacy and safety of switch maintenance therapy with gatipotuzumab in patients with TA-MUC1-positive recurrent ovarian, fallopian tube, or primary high-grade serous peritoneal cancer. PATIENTS AND METHODS: In this double-blind, randomized, placebo-controlled, phase II trial, patients with at least stable disease (SD) following chemotherapy were randomized 2:1 to receive intravenous gatipotuzumab (500 mg followed by 1700 mg 1 week later) or placebo every 3 weeks until tumor progression or unacceptable toxicity occurred. Stratification factors were the number of prior chemotherapy lines (2 versus 3-5), response versus SD after the most recent chemotherapy, and progression-free survival (PFS) <6 versus 6-12 months following the prior therapy. Primary endpoint was PFS according to modified immune-related RECIST 1.1 response criteria. Secondary endpoints were PFS at 6 months, safety, overall response rate, CA-125 progression, overall survival, quality of life, and pharmacokinetics. RESULTS: Overall, 216 patients were randomized to gatipotuzumab (n  = 151) or placebo (n  = 65). Median PFS with gatipotuzumab was 3.5 months as compared with 3.5 months with placebo (hazard ratio 0.96, 95% confidence interval 0.69-1.33, P  = 0.80). No advantage for gatipotuzumab over placebo was seen in the secondary efficacy endpoints or in any stratified subgroups. Gatipotuzumab was well tolerated, with mild to moderate infusion-related reactions being the most common adverse events. CONCLUSIONS: Gatipotuzumab switch maintenance therapy does not improve outcome in TA-MUC1-positive ovarian cancer patients. TRIAL REGISTRATION: ClinicalTrials.govNCT01899599; https://clinicaltrials.gov/ct2/show/NCT01899599.

Study protocol: understanding the pathophysiologic mechanisms underlying delirium in older people undergoing hip fracture surgery.

BACKGROUND: Postoperative delirium (POD) is a common complication of older people undergoing hip fracture surgery, which negatively affects clinical- and healthcare-related outcomes. Unfortunately, POD pathophysiology is still largely unknown, despite previous studies showing that neuroinflammation, neuroendocrine dysfunction, increased reactive oxidative stress (ROS), and endothelial dysfunctions may be involved. There is also evidence that many of the pathophysiological mechanisms which are involved in delirium are involved in sarcopenia too. This article describes the protocol of a pilot study to evaluate the feasibility of a larger one that will explore the pathophysiological mechanisms correlating POD with sarcopenia. We will analyse whether various biomarkers reflecting neuroinflammation, ROS, neuroendocrine disorders, and microvasculature lesions will be simultaneously expressed in in the blood, cerebrospinal fluid (CSF), and muscles of patients developing POD. METHODS: Two centres will be involved in this study, each recruiting a convenient sample of ten older patients with hip fracture. All of them will undergo a baseline Comprehensive Geriatric Assessment, which will be used to construct a Rockwood-based Frailty Index (FI). Blood samples will be collected for each patient on the day of surgery and 1 day before. Additionally, CSF and muscle fragments will be taken and given to a biologist for subsequent analyses. The presence of POD will be assessed in each patient every morning until hospital discharge using the 4AT. Delirium subtypes and severity will be assessed using the Delirium Motor Subtype Scale-4 and the Delirium-O-Meter, respectively. We will also evaluate the patient's functional status at discharge, using the Cumulated Ambulation Score. DISCUSSION: This study will be the first to correlate biomarkers of blood, CSF, and muscle in older patients with hip fracture.

A randomized phase II study comparing the efficacy and safety of the glyco-optimized anti-EGFR antibody tomuzotuximab against cetuximab in patients with recurrent and/or metastatic squamous cell cancer of the head and neck - the RESGEX study.

BACKGROUND: The aim of the RESGEX study was to compare the efficacy and safety of the anti-epidermal growth factor receptor (anti-EGFR) antibody tomuzotuximab against cetuximab both in combination with chemotherapy in patients with recurrent and/or metastatic squamous cell cancer of the head and neck in the first-line treatment. PATIENTS AND METHODS: In this phase II trial 240 patients were equally randomized for six cycles to receive either tomuzotuximab (initial dose 990 mg then 720 mg) weekly and cisplatin 100 mg/m2 and fluorouracil (5-FU; 1000 mg/m2/day, days 1-4) every 3 weeks or cetuximab (400 mg/m2 subsequent 250 mg/m2) weekly with the same chemotherapeutic backbone followed by antibody maintenance treatment. The primary endpoint was progression-free survival. RESULTS: Median progression-free survival was 6.5 months [95% confidence interval (CI) 5.9-7.9 months] in the tomuzotuximab group and 6.2 months (95% CI 5.8-7.3 months) in the cetuximab group (P = 0.86). The median overall survival (OS) estimate was 11.6 months (95% CI 9.5-17.2 months) in the tomuzotuximab group and 13.8 months (95% CI 12.3-16.4 months) in the cetuximab group (P = 0.96). In an exploratory analysis a small subgroup of p16-positive patients had a significantly longer OS compared with p16-negative patients (hazard ratio 1.860, 95% CI 1.09-3.16, P = 0.02). CONCLUSIONS: The glyco-engineered antibody tomuzotuximab failed to demonstrate improved efficacy with a chemotherapeutic backbone in the first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma. It remains a so far unanswered question whether such antibody would partner better with different drugs such as checkpoint inhibitors.

Modifiable and non-modifiable risk factors affecting walking recovery after hip fracture.

UNLABELLED: Modifiable and non-modifiable predictors of mobility recovery were analyzed on a sample of 774 hip fracture patients according to pre-fracture abilities. Overall predictors were mostly non-modifiable factors related to frailty of patients with the exception of 25-hydroxyvitamin D concentration which significantly affected walking recovery, especially in patients with higher pre-fracture performance. INTRODUCTION: This study aims to investigate mobility changes after hip fracture with the aim of identifying modifiable and non-modifiable predictors of mobility recovery according to different pre-fracture abilities. METHODS: This is a prospective inception cohort study of consecutive older patients, admitted with a fragility hip fracture in three Hospitals of Emilia Romagna (Italy). A sample of 774 patients alive at the sixth month was divided into three groups according to pre-fracture ambulation ability (group 1: mobile outdoors; group 2: mobile indoors; and group 3: mobile with help). The relationship between baseline characteristics of patients and the odds of walking recovery was analyzed using multivariate regression analysis. RESULTS: Mortality differed significantly among the three groups and was the highest in patients needing help to walk. Among the survivors, only 50.3 % of patients recovered walking ability. In a multivariate analysis, independent risk factors were different among the three groups. In group 1, older age, comorbidities, the use of walking devices before fracture, and low albumin level acted as negative factors while male gender, a pre-fracture high functional status, and higher 25-hydroxyvitamin D levels increased the probability of full recovery. In group 2, only pre-fracture functional status and 25-hydroxyvitamin D concentration were related to the recovery of walking ability. Pre-fracture functional status was also the only significant predictor for patients in group 3. CONCLUSIONS: Several baseline characteristics of patients are related to the likelihood of recovering walking ability after hip fracture. The 25-hydroxyvitamin D level seems to be the only relevant modifiable factor even if the effectiveness of its supplementation has yet to be demonstrated.

High serum uric acid levels increase the risk of metabolic syndrome in elderly women: The PRO.V.A study.

BACKGROUND AND AIMS: Serum uric acid (SUA) is the end-product of purine metabolism in humans, and its levels often increase in subjects with metabolic syndrome (MetS). Despite several studies demonstrating a relationship between increased SUA levels and the prevalence of MetS, prospective data on SUA as a predictor of the incidence of MetS in the elderly are limited. Our aim was to conduct a prospective study on the association between SUA concentrations and the onset of MetS in an elderly Italian cohort. METHODS AND RESULTS: This is a cohort study (Progetto Veneto Anziani; Pro.V.A.) involving community-dwelling subjects aged ≥65 years and followed up for a mean 4.4 years. We included 1128 participants (aged 74.7 ± 7.1 years) without MetS at the baseline. Gender-specific SUA groups according to the standard deviation (SD) from the mean were considered, taking the incidence of MetS as the main outcome. The mean SUA level was significantly higher in men than in women (5.4 ± 1.2 vs. 4.5 ± 1.2 mg/dl; p < 0.0001). Over the 4.4-year follow-up, 496 individuals developed MetS. After adjusting for potential confounders, Cox's regression analysis revealed no relationship between higher baseline SUA concentrations and the incidence of MetS in men or in the sample as whole, while women with SUA levels more than 1 SD above the mean (≥5.7 mg/dl) carried a 58% higher risk (95%CI: 1.03-2.40; p = 0.03) of being newly diagnosed with MetS during the follow-up. CONCLUSION: High SUA levels significantly and independently predicted MetS in older women, but not in men, over a 4.4-year follow-up.

Vitamin D supplementation is required to normalize serum level of 25OH-vitamin D in older adults: an observational study of 974 hip fracture inpatients.

BACKGROUND: Vitamin D deficiency is highly prevalent in older adults in all continents. In this study we assessed the vitamin D status of hip fracture subjects across different hospitals in a real word situation using the data from a multicenter cohort study on outcomes in orthogeriatric units. METHODS: We performed a prospective cohort study on 974 consecutive patients 75 yr or older admitted with fragility hip fracture over a 12 months period at 4 general hospitals of different districts in Emilia Romagna Region, Italy. Data collected included comorbidity, cognitive impairment, prefracture functional status, walking ability, living arrangement along with the use of antiosteoporotic drugs, serum intact PTH and serum 25-hydroxyvitamin D [25(OH)D]. RESULTS: Mean 25(OH)D serum levels were 12.2±9.4 ng/ml and 84.2% of patients had levels below recommended values. Male had a higher probability to have values within the reference range [odds ratio (OR): 1.74 (1.13-2.67); p=0.012] while living in nursing resulted negatively related even if only close to statistical significance [OR: 0.24 (0.06-1.02); p=0.051]. Vitamin D supplementation appeared to be the strongest factor associated with adequate level of vitamin D levels [OR: 4.50 (2.57-7.88); p<0.001). CONCLUSION: This study confirmed the very high rate of severe vitamin D deficiency in Italian subjects admitted with hip fracture. Our study also showed that supplementation of vitamin D is the strongest determinant influencing serum 25(OH)D level of older persons with hip fracture and these results should be taken into account when planning treatment in older persons.

Markers of endothelial dysfunction in older subjects with late onset Alzheimer's disease or vascular dementia.

A consistent amount of evidence suggests that vascular factors might be involved in the pathogenesis of late onset Alzheimer's disease (LOAD). We evaluated the presence of endothelial dysfunction by measuring the plasma levels of soluble E-selectin and vascular cell adhesion molecule 1 (VCAM-1) in a sample of patients affected by LOAD (n. 60) or vascular dementia (VD: n. 80). They were compared with a sample of older patients with cerebrovascular disease but not-dementia (CDND: n. 40), and with a sample of healthy older controls (n. 30). sVCAM-1 plasma levels were higher in LOAD and VD compared with controls. Among patients (LOAD, VD, and CDND), sE-selectin levels were higher in individuals with most severe cerebrovascular disease on CT scan. At multivariate regression analysis, fasting glucose (p<0.05) and TNF-alpha levels (p<0.02) were positively correlated with sE-selectin levels (adjusted r(2): 20%), while sVCAM-1 was positively correlated with age (p<0.01), and alcohol consumption (p: 0.03), and negatively associated with HDL-C levels (p: 0.005), (p<0.01; adjusted r(2): 44%), independent of possible confounders. Increased sVCAM-1 plasma levels in LOAD and VD suggest the existence of endothelial dysfunction in both types of dementia. The possible role of E-selectin in the pathogenesis of cerebrovascular disease is also supported by our data.

Plasma cytokines profile in older subjects with late onset Alzheimer's disease or vascular dementia.

Some cytokines have been involved in the pathogenesis of late onset Alzheimer's disease (LOAD). A possible increase in plasma cytokines levels has been reported in LOAD and vascular dementia (VD), but the results of previous studies are conflicting. We evaluated the plasma levels of IL-6, TNF-alpha, IL-1beta, and IL-10 in four groups of older individuals: 60 patients with LOAD, 80 patients with VD, 40 subjects with cerebrovascular disease but without dementia (CDND), and 42 controls (C). By analysis of covariance (adjustment for age, gender, coronary heart disease, diabetes, hypertension, smoking, and alcohol consumption) we found that: *IL-1beta was higher in VD, LOAD, and CDND compared with controls (p<0.005). *TNF-alpha was higher in VD and LOAD compared to C (p<0.05), and in VD compared to LOAD (p<0.03). *IL-6 was higher in VD compared with LOAD (p<0.03). No differences in IL-10 values were found (Kruskal-Wallis, Asymp. Sig. 0.14). By logistic regression analysis, we demonstrated that high levels (defined as above the median) of IL-1beta and TNF-alpha, but not of IL-6, were associated with increased likelihood of having VD and LOAD compared to C, while high IL-6 levels were associated with a increased probability of having VD, compared with LOAD. Our study support the notion of a low-grade systemic inflammation in older patients with LOAD or VD, characterized by an increase in plasma IL-1beta and TNF-alpha levels. The high IL-6 levels found in VD might be not a specific finding, as it might come from several conditions including atherosclerosis and related vascular risk factors, comorbidity, and frailty.

High interleukin-6 plasma levels are associated with functional impairment in older patients with vascular dementia.

In older individuals, inflammatory mechanisms have been linked to the pathogenesis of both dementia and functional impairment. In this cross-sectional study we have investigated the possible association between some markers of systemic inflammation and functional status, in a sample of one hundred and forty older demented patients including 60 patients with late onset Alzheimer's disease (LOAD) and 80 with vascular dementia (VD). Functional status was evaluated by Barthel Index (BI); the total score ranged from 0 (total dependency) to 20 (total autonomy). Interleukin-1beta, Tumor Necrosis Factor-alpha, Interleukin- 6, Interleukin- 8, and Transforming Grow Factor beta were quantified by ELISA. Among the cytokines evaluated, only IL-6 was correlated with the BI (r: -0.32, p < 0.001). The mean levels of IL-6 progressively decreased from I (9.50 pg/mL), to II (6.40 pg/mL), to III BI tertile (4.80 pg/mL) (p < 0.02). At multiple regression analysis, IL-6 was associated with BI in the whole sample and in VD, but not in LOAD, independent of age, gender, smoking, alcohol consumption, hypertension, diabetes, coronary heart disease, previous stroke, and mini mental state examination score. Our study suggests the existence of an independent and negative relationship between IL-6 plasma levels and functional status in older individuals with vascular dementia. This finding might contribute to explain the 'excess of disability' phenomenon described in older demented patients.

Leukoaraiosis is associated with functional impairment in older patients with Alzheimer's disease but not vascular dementia.

BACKGROUND: Leukoaraiosis (LA) is a common finding in older persons, and might be associated with reduced cognitive performance, gait abnormalities, and functional impairment. Although LA is more frequent in persons affected by dementia, scant data are available about its clinical consequences in this group of patients. OBJECTIVE: To study the association between presence of LA and functional performance in basic activities of daily living in a sample of older persons affected by dementia. DESIGN: We conducted a cross-sectional study on 214 patients; 77 affected by late onset Alzheimer's disease (LOAD), and 137 by vascular dementia (VD). Functional status was assessed using Barthel Index (BI). LA was assessed using computed tomography. RESULTS: In LOAD patients, LA (OR: 7.87; 1.26-48.94), and MMSE score (OR: 0.83; 0.71-0.98) were associated with the risk of severe disability, independent of age, gender, diabetes, hypertension, coronary heart disease, left ventricular hypertrophy, atrial fibrillation, and brain atrophy. In VD patients, MMSE score (OR: 0.77; 0.64-0.93), and CHD (OR: 7.41; 1.09-50.21), but not LA (OR: 2.07; 0.45-9.45) were associated with a severe functional impairment after multivariate adjustment. CONCLUSIONS: Our study suggests that LA might be associated with a worse functional status in basic activities of daily living in patients affected by LOAD but not VD. LA might act synergistically with cognitive and behavioural disturbances to the onset and progression of disability of these patients.

Phase III trial of satraplatin, an oral platinum plus prednisone vs. prednisone alone in patients with hormone-refractory prostate cancer.

Satraplatin is a novel oral platinum (IV) complex that shows activity against hormone-refractory prostate cancer (HRPC) in cisplatin-resistant human tumor lines in phase I and phase II trials. A randomized multicenter phase III trial with a target sample size of 380 patients was initiated in men with HRPC. After 50 randomized patients, the trial was closed to further accrual by the sponsoring company. An ad hoc analysis of all available data is reported here. Eligibility criteria included pathological proof of prostate cancer, documented progression despite prior hormonal manipulation, WHO PS 0-2, and no daily intake of narcotic analgesics. Patients were randomized between satraplatin 100 mg/m(2) for 5 days plus prednisone 10 mg orally BID or prednisone alone. Compliance was excellent. 48/50 patients have progressed and 42 have died, mostly due to prostate cancer. Median overall survival was 14.9 months (95% CI: 13.7-28.4) on the satraplatin plus prednisone arm and 11.9 months (95% CI: 8.4-23.1) on prednisone alone (hazard ratio, HR = 0.84, 95% CI: 0.46-1.55). A >50% decrease in prostrate specific antigen (PSA) was seen in 9/27 (33.3%) in the satraplatin plus prednisone arm vs. 2/23 (8.7%) on the prednisone alone arm. Progression-free survival was 5.2 months (95% CI: 2.8-13.7) on the satraplatin plus prednisone arm as compared to 2.5 months (95% CI: 2.1- 4.7) on the prednisone alone arm (HR = 0.50, 95% CI: 0.28-0.92). This difference is statistically significant (p = 0.023). Toxicity was generally minimal in both arms. This randomized comparison of a combination of satraplatin and prednisone versus prednisone alone supports the antitumor activity of the combination. Its role in the treatment of HPRC remains to be elucidated in an appropriate phase III setting.

Acute toxicity of conventional radiation therapy for high-risk prostate cancer in EORTC trial 22863.

OBJECTIVES: We analysed the acute toxicity observed in the European Organisation for Research and Treatment of Cancer (EORTC) randomised trial 22863 comparing conventional external irradiation with or without an agonist analogue of gonadotropin-releasing hormone in high-risk prostate cancer patients. METHODS: Four hundred five patients that received a dose of at least 30 Gy were considered evaluable for acute toxicity assessment. Toxicity was grouped in a few categories: general, genito-urinary, and lower gastro-intestinal. Univariate and multivariate analyses were performed using the World Health Organisation (WHO) toxicity score and grouping together toxicity scores in different bimodal and trimodal groups. RESULTS: Overall, our data show that age, previous surgery and irradiation dose are important predictive factors for acute toxicity, but not the use of combined hormone therapy. Fifteen percent of patients suffered of moderate to severe acute toxicity (WHO G3-G4). Life threatening toxicity was observed in six cases (1.5%). CONCLUSIONS: The assessment of toxicity combining in different groups the original five scores scale produced conflicting results similar to those commonly reported in literature. Interpretation of the role of pre-treatment factors with uneven distribution in the study requires careful evaluation. These data obtained with conventional curative irradiation of high-risk prostate cancer patients are proposed for comparison with results achieved using modern state-of-the-art irradiation techniques.

The EORTC Boron Neutron Capture Therapy (BNCT) Group: achievements and future projects.

Boron Neutron Capture Therapy (BNCT) is an experimental treatment modality that takes place in a nuclear research reactor. To progress from preclinical studies to patient treatment is a challenge requiring strict quality management and special solutions to licensing, liability, insurance, responsibility and logistics. The European Organisation for the Research and Treatment of Cancer (EORTC) BNCT group has started the first European clinical trial of BNCT for glioblastoma patients at the European High Flux Reactor (HFR) in Petten, The Netherlands, conducted by the Department of Radiotherapy of the University of Essen, Germany. A very strict quality management had to be installed following the European rules on safety and quality assurance for nuclear research reactors, for radioprotection, for radiotherapy and for clinical trials. The EORTC BNCT Group has created a virtual European-wide hospital to handle the complex management of patients treated with BNCT. New clinical trials are currently under development.

The EORTC Genito-Urinary Tract Cancer Group: 25 years of achievements and future strategies.

The European Organisation for Research and Treatment of Cancer (EORTC) Genito-Urinary (GU) Tract Cancer Group celebrates 25 years of activity in 2001. The Group has developed an intense research activity carrying out phase II and phase III clinical trials in prostate, bladder, renal, penile and testicular cancers. It is one of the most active groups within the EORTC, entering more than 1200 new patients in its trials in 2001. In its trials, the EORTC GU Group also focuses on quality control, quality of life and uro-pathology. Besides collaboration with other EORTC groups, the GU Group is very actively collaborating with international organisations. Currently, several large phase III studies are conducted in collaboration with European and North American organisations. For the next few years, the Group is committed to develop projects aimed at testing new drugs and therapeutic strategies and increasing the collaboration between basic science and clinical practice.

EORTC Radiotherapy Group: achievements and future projects. European Organisation for Research and Treatment of Cancer.

The European Organisation for Research and Treatment of Cancer (EORTC) Radiotherapy (RT) Group will celebrate 27 years of activity in 2002. During its long history, the Radiotherapy Group has conducted a large number of studies which have provided valuable information on the radiation treatment of several disease sites. Group efforts have been concentrated on dose-effect studies, optimal fractionation schemes, combinations with other treatment modalities, and new radiotherapy techniques. The EORTC RT Group was the first in Europe to develop and introduce methodologies of Quality Assurance in radiotherapy. The RT Group actively collaborates with other EORTC Groups and international organisations. Currently, several phase III studies are being conducted in collaboration with European, North American and Australian organisations. The collaboration with RTOG led to the setting up of common systems for scoring late normal tissue effects. In the years to come, the Group will keep pioneering pivotal trials in radiotherapy and radio-chemotherapy. It will also explore combinations with novel therapies in phase I trials and implement innovative translational research programmes.

Addressing the challenge of intergroup studies in oncology: the EORTC experience. European Organisation for Research and Treatment of Cancer.

Intergroup studies are conducted by more than one clinical research group. There are several difficulties that hamper in practice the possibility of conducting such trials, as all interested parties will have to address unusual and complex issues. These are mainly related to differences in size, interests, motivations and means among different research organisations. The EORTC recognises the importance to promote intergroup collaboration providing to all interested groups the necessary expertise and organisational support to conduct intergroup studies. The role of the EORTC evolved from the spontaneous organisations of intergroup trials to the definition of a basic set of principles and criteria that groups have to fulfil to participate in intergroup trials. Recently, a specific EORTC Intergroup Office started its activity devoted to solve the issues related to the intergroup co-operation. This office will have an increasing role to promote and help in conducting intergroup studies.