European Organisation Of Research And Treatment Of Cancer Research Articles

Adjuvant immunotherapy in patients with resected gastric and oesophagogastric junction cancer following preoperative chemotherapy with high risk for recurrence (ypN+ and/or R1): European Organisation of Research and Treatment of Cancer (EORTC) 1707 VESTIGE study.

Patients with gastroesophageal adenocarcinoma with tumour-positive lymph nodes (ypN+) or positive surgical margins (R1) following neoadjuvant chemotherapy and resection are at high risk of recurrence. Adjuvant nivolumab is effective in oesophageal/oesophagogastric junction cancer and residual pathological disease following chemoradiation and surgery. Immune checkpoint inhibition has shown efficacy in advanced gastroesophageal cancer. We hypothesised that nivolumab/ipilimumab would be more effective than adjuvant chemotherapy in high-risk (ypN+ and/or R1) patients with gastroesophageal adenocarcinoma following neoadjuvant chemotherapy and resection. VESTIGE was an academic international, multicentre, open-label, randomised phase II trial evaluating the efficacy of adjuvant nivolumab/ipilimumab versus chemotherapy in gastroesophageal adenocarcinoma at high risk of recurrence. Patients were randomised 1:1 to receive standard adjuvant chemotherapy (same regimen as neoadjuvant) or nivolumab 3 mg/kg IV every 2 weeks plus ipilimumab 1 mg/kg IV every 6 weeks for 1 year. Key inclusion criteria included ypN+ and/or R1 status after neoadjuvant chemotherapy plus surgery. The primary endpoint was disease-free survival in the intent-to-treat population. Secondary endpoints included overall survival, loco-regional and distant failure rates and safety according to NCI-CTCAE v5.0. The independent Data Monitoring Committee reviewed data from 189 of the planned 240 patients in June 2022 and recommended stopping recruitment due to futility. At the time of final analysis, median follow-up was 25.3 months for 195 patients (98 nivolumab/ipilimumab and 97 chemotherapy). Median disease-free survival for the nivolumab/ipilimumab group was 11.4 months (95% confidence interval [CI], 8.4-16.8 months) versus 20.8 months (95% CI, 15.0-29.9 months) for the chemotherapy group, HR 1.55 (95% CI, 1.07- 2.25, one-sided P=0.99). The 12-month disease-free survival rates were 47.1% and 64.0%, respectively. There were no toxicity concerns or excess early discontinuations. Nivolumab/ipilimumab did not improve disease-free survival compared to chemotherapy in patients with ypN+ and/or R1 gastroesophageal adenocarcinoma following neoadjuvant chemotherapy and surgery.

European consensus-based interdisciplinary guideline for invasive cutaneous squamous cell carcinoma: Part 2. Treatment–Update 2023

In order to update recommendations on treatment, supportive care, education, and follow-up of patients with invasive cutaneous squamous cell carcinoma (cSCC), a multidisciplinary panel of experts from the European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF), the European Society for Radiotherapy and Oncology (ESTRO), the European Union of Medical Specialists (UEMS), the European Academy of Dermatology and Venereology (EADV), and the European Organisation of Research and Treatment of Cancer (EORTC) was formed. Recommendations were based on an evidence-based literature review, guidelines, and expert consensus. Treatment recommendations are presented for common primary cSCC (low risk, high risk), locally advanced cSCC, regional metastatic cSCC (operable or inoperable), and distant metastatic cSCC. For common primary cSCC, the first-line treatment is surgical excision with postoperative margin assessment or micrographically controlled surgery. Achieving clear surgical margins is the most important treatment consideration for patients with cSCCs amenable to surgery. Regarding adjuvant radiotherapy for patients with high-risk localised cSCC with clear surgical margins, current evidence has not shown significant benefit for those with at least one high-risk factor. Radiotherapy should be considered as the primary treatment for non-surgical candidates/tumours. For cSCC with cytologically or histologically confirmed regional nodal metastasis, lymph node dissection is recommended. For patients with metastatic or locally advanced cSCC who are not candidates for curative surgery or radiotherapy, anti-PD-1 agents are the first-line systemic treatment, with cemiplimab being the first approved systemic agent for advanced cSCC by the Food and Drugs Administration/European Medicines Agency. Second-line systemic treatments for advanced cSCC, include epidermal growth factor receptor inhibitors (cetuximab) combined with chemotherapy or radiotherapy. Multidisciplinary board decisions are mandatory for all patients with advanced cSCC, considering the risks of toxicity, the age and frailty of patients, and co-morbidities, including immunosuppression. Patients should be engaged in informed, shared decision-making on management and be provided with the best supportive care to improve symptom management and quality of life. The frequency of follow-up visits and investigations for subsequent new cSCC depends on underlying risk characteristics.

European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 1. epidemiology, diagnostics and prevention

Invasive cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in the white populations, accounting for 20% of all cutaneous malignancies. Factors implicated in cSCC etiopathogenesis include ultraviolet radiation exposure and chronic photoaging, age, male sex, immunosuppression, smoking and genetic factors. A collaboration of multidisciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organisation of Research and Treatment of Cancer (EORTC) was formed to update recommendations on cSCC classification, diagnosis, risk stratification, staging and prevention, based on current literature, staging systems and expert consensus. Common cSCCs are typically indolent tumors, and most have a good prognosis with 5-year cure rates of greater than 90%, and a low rate of metastases (<4%). Further risk stratification into low-risk or high-risk common primary cSCC is recommended based on proposed high-risk factors. Advanced cSCC is classified as locally advanced (lacSCC), and metastatic (mcSCC) including locoregional metastatic or distant metastatic cSCC. Current systems used for staging include the American Joint Committee on Cancer (AJCC) 8th edition, the Union for International Cancer Control (UICC) 8th edition, and Brigham and Women’s Hospital (BWH) system. Physical examination for all cSCCs should include total body skin examination and clinical palpation of lymph nodes, especially of the draining basins. Radiologic imaging such as ultrasound of the regional lymph nodes, magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography–computed tomography (PET-CT) scans are recommended for staging of high-risk cSCC. Sentinel lymph node biopsy is currently not recommended. Nicotinamide, oral retinoids, and topical 5-FU have been used for the chemoprevention of subsequent cSCCs in high-risk patients but are not routinely recommended. Education about sun protection measures including reducing sun exposure, use of protective clothing, regular use of sunscreens and avoidance of artificial tanning, is recommended.

Development and Psychometric Evaluation of an Item Bank for Computerized Adaptive Testing of the EORTC Insomnia Dimension in Cancer Patients (EORTC CAT-SL)

To further advance assessment of patient-reported outcomes, the European Organisation of Research and Treatment of Cancer (EORTC) Quality of Life Group has developed computerized adaptive test (CAT) versions of all EORTC Quality of Life Core Questionnaire (QLQ-C30) scales/items. The aim of this study was to develop and evaluate an item bank for CAT measurement of insomnia (CAT-SL). In line with the EORTC guidelines, the developmental process comprised four phases: (I) defining the concept insomnia and literature search, (II) selection and formulation of new items, (III) pre-testing and (IV) field-testing, including psychometric analyses of the final item bank. In phase I, the literature search identified 155 items that were compatible with our conceptualisation of insomnia, including both quantity and quality of sleep. In phase II, following a multistep-approach, this number was reduced to 15 candidate items. Pre-testing of these items in cancer patients (phase III) resulted in an item list of 14 items, which were field-tested among 1094 patients in phase IV. Psychometric evaluations showed that eight items could be retained in a unidimensional model. The final item bank yielded greater measurement precision than the original QLQ-C30 insomnia item. It was estimated that administering two or more items from the insomnia item bank with CAT results in a saving in sample size between approximately 15–25%. The 8-item EORTC CAT-SL item bank facilitates precise and efficient measurement of insomnia as part of the EORTC CAT system of health-related quality life assessment in both clinical research and practice.

GR01.05 Site of Oligometastases

GR01.05 Site of Oligometastases

Psychometric evaluation of an item bank for computerized adaptive testing of the EORTC QLQ-C30 cognitive functioning dimension in cancer patients

BackgroundThe European Organisation of Research and Treatment of Cancer (EORTC) Quality of Life Group is developing computerized adaptive testing (CAT) versions of all EORTC Quality of Life Questionnaire (QLQ-C30) scales with the aim to enhance measurement precision. Here we present the results on the field-testing and psychometric evaluation of the item bank for cognitive functioning (CF).MethodsIn previous phases (I–III), 44 candidate items were developed measuring CF in cancer patients. In phase IV, these items were psychometrically evaluated in a large sample of international cancer patients. This evaluation included an assessment of dimensionality, fit to the item response theory (IRT) model, differential item functioning (DIF), and measurement properties.ResultsA total of 1030 cancer patients completed the 44 candidate items on CF. Of these, 34 items could be included in a unidimensional IRT model, showing an acceptable fit. Although several items showed DIF, these had a negligible impact on CF estimation. Measurement precision of the item bank was much higher than the two original QLQ-C30 CF items alone, across the whole continuum. Moreover, CAT measurement may on average reduce study sample sizes with about 35–40% compared to the original QLQ-C30 CF scale, without loss of power.ConclusionA CF item bank for CAT measurement consisting of 34 items was established, applicable to various cancer patients across countries. This CAT measurement system will facilitate precise and efficient assessment of HRQOL of cancer patients, without loss of comparability of results.

A randomised, placebo-controlled trial assessing the efficacy of an oral B group vitamin in preventing the development of chemotherapy-induced peripheral neuropathy (CIPN).

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect resulting from neurotoxic chemotherapeutic agents. This study aimed to assess the efficacy and safety of an oral B group vitamin compared to placebo, in preventing the incidence of CIPN in cancer patients undergoing neurotoxic chemotherapy. A pilot, randomised, placebo-controlled trial was conducted. Newly diagnosed cancer patients prescribed with taxanes, oxaliplatin or vincristine were invited to participate. A total of 71 participants (female 68%, male 32%) were enrolled into the study and randomised to the B group vitamin (n=38) arm or placebo (n=33). The data from 47 participants were eligible for analysis (B group vitamins n=27, placebo n=22). The primary outcome measure was the total neuropathy score assessed by an independent neurologist. Secondary outcome measures included serum vitamin B levels, quality of life, pain inventory and the patient neurotoxicity questionnaires. Outcome measures were conducted at baseline, 12, 24 and 36weeks. The total neuropathy score (TNS) demonstrated that a B group vitamin did not significantly reduce the incidence of CIPN compared to placebo (p=0.73). Statistical significance was achieved for patient perceived sensory peripheral neuropathy (12weeks p=0.03; 24weeks p=0.005; 36weeks p=0.021). The risk estimate for the Patient Neurotoxicity Questionnaire (PNQ) was also statistically significant (OR=5.78, 95% CI=1.63-20.5). The European Organisation of Research and Treatment of Cancer (EORTC) quality of life, total pain score and pain interference showed no significance (p=0.46, p=0.9, p=0.37 respectively). A trend was observed indicating that vitamin B12 may reduce the onset and severity of CIPN. An oral B group vitamin as an adjunct to neurotoxic chemotherapy regimens was not superior to placebo (p>0.05) for the prevention of CIPN. Patients taking the B group vitamin perceived a reduction in sensory peripheral neuropathy in the PNQ. Moreover, a robust clinical study is warranted given that vitamin B12 may show potential in reducing the onset and severity of CIPN. Trial number: ACTRN12611000078954 Protocol number: UH2010000749.

PRO-ONKO-selection of patient-reported outcome assessments for the clinical use in cancer patients-a mixed-method multicenter cross-sectional exploratory study.

Cancer patients frequently suffer from multiple symptoms often impairing functional status and health-related quality of life (HRQOL). A comprehensive assessment including patient-reported outcomes (PROs) is recommended to enable individualized supportive care. However, PRO assessments are still not part of routine clinical practice. Therefore, this project aimed to compile an item pool from validated assessment instruments to facilitate the use of PROs for clinical decision-making in oncology clinics. This qualitative dominant mixed-method cross-sectional exploratory study was carried out in four centers and comprised two stages. Stage I: Six interdisciplinary focus groups were conducted to choose questionnaires meeting particular clinical requirements. Stage II: Adult patients with heterogeneous cancer diagnoses, receiving in- or out-patient treatment were asked to participate and complete the chosen questionnaires (participation 71/74). Resulting PROs were compared with clinical records. Health care professionals (HCPs) and patients rated the usefulness for routine clinical practice. The European Organisation of Research and Treatment of Cancer (EORTC) QLQ-C30 and Distress Thermometer were chosen for screening and M.D. Anderson Symptom Inventory (MDASI) and EORTC single items for monitoring. Comparison of n = 88 PRO assessments with clinical records showed consistent documentation of side effects like fever and emesis. Symptoms like fatigue, sadness, or sleep disturbance were not documented regularly in the medical records but captured by PRO assessments. Patients and HCPs judged the chosen questionnaires and electronic data collection as useful. Future studies should examine how PROs can complement or substitute routine documentation in order to achieve standardized assessment and documentation during the treatment process in different settings and examine possible benefits for patients.

Cancer survivorship: A positive side-effect of more successful cancer treatment

Over the past decades, early diagnosis, new drugs and more personalised multi-modality treatment have led to impressive increases in survival rates of patients with cancer. This success in treating cancer has resulted in a large and rapidly increasing number of cancer survivors, yet life after cancer is often compromised by a broad spectrum of late adverse treatment effects. Some encounter cardiovascular, second malignancies, cognitive or other morbidities which impair normal life in an important way. Some patients are confronted with societal discrimination due to slower performance, chronic fatigue or partial inability and these things can adversely affect employment, education, insurance or mortgage opportunities.In 2012, the European Organisation of Research and Treatment of Cancer (EORTC) Survivorship Task Force was created to focus research efforts on late morbidity of cancer treatment and its impact on society. On 30–31st January 2014, the 1st EORTC Cancer Survivorship Summit was organised to facilitate interaction between clinicians, researchers, social workers, patients, insurers, bankers and policy makers. This important event addressed the needs of cancer survivors, and new collaborations between academic groups, patient advocates, financial and political representatives were formed to guide future European research and health policies in this field. This special issue of the European Journal of Cancer is entirely dedicated to this Summit and addresses, respectively, second malignancies, cardiovascular disease, cognitive dysfunction, infertility/sexuality and psycho-social problems following cancer treatment.

EORTC risk tables – their usefulness in the assessment of recurrence and progression risk in non–muscle–invasive bladder cancer in Polish patients

IntroductionThe assessment of risk of recurrence and progression of bladder cancer (BC) is still rather difficult. We decided to check the rates of the changes mentioned above in the group of the Polish patients after a year–long observation and next to compare them with the results calculated in the European Organisation of Research and Treatment of Cancer (EORTC) risk tables.MethodsThe tested group consisted of 91 patients who underwent transurethral resection of bladder tumour (TURBT). When being diagnosed, 60 cases were in the pTa clinical stage, whereas 30 cases were in T1. The coexisting carcinoma in situ (CIS) was observed in four cases. On the basis of the scores obtained from the EORTC tables, the patients were divided into the groups of low, intermediate or high risk of disease recurrence and progression.ResultsRecurrence was noticed in 23 patients (25%), while progression was observed in 11 patients (12.1%). The rate of the observed recurrences proved to be lower than it had been predicted in all the groups, except for one of the intermediate–risk group (score 1– 4). Moreover, the rate of the progressions predicted according to the EORTC risk tables was higher in all the risk groups.ConclusionsIt can be noticed that the rate of real recurrences is lower than expected, whereas the rate of the observed progressions is overestimated. Partly, it could be the result of using a relatively small group of patients for observation and applying a different method of treatment.

Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft-tissue sarcoma: a randomised phase 3 multicentre study

The optimum treatment for high-risk soft-tissue sarcoma (STS) in adults is unclear. Regional hyperthermia concentrates the action of chemotherapy within the heated tumour region. Phase 2 studies have shown that chemotherapy with regional hyperthermia improves local control compared with chemotherapy alone. We designed a parallel-group randomised controlled trial to assess the safety and efficacy of regional hyperthermia with chemotherapy. Patients were recruited to the trial between July 21, 1997, and November 30, 2006, at nine centres in Europe and North America. Patients with localised high-risk STS (> or = 5 cm, Fédération Nationale des Centres de Lutte Contre le Cancer [FNCLCC] grade 2 or 3, deep to the fascia) were randomly assigned to receive either neo-adjuvant chemotherapy consisting of etoposide, ifosfamide, and doxorubicin (EIA) alone, or combined with regional hyperthermia (EIA plus regional hyperthermia) in addition to local therapy. Local progression-free survival (LPFS) was the primary endpoint. Efficacy analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT 00003052. 341 patients were enrolled, with 169 randomly assigned to EIA plus regional hyperthermia and 172 to EIA alone. All patients were included in the analysis of the primary endpoint, and 332 patients who received at least one cycle of chemotherapy were included in the safety analysis. After a median follow-up of 34 months (IQR 20-67), 132 patients had local progression (56 EIA plus regional hyperthermia vs 76 EIA). Patients were more likely to experience local progression or death in the EIA-alone group compared with the EIA plus regional hyperthermia group (relative hazard [RH] 0.58, 95% CI 0.41-0.83; p=0.003), with an absolute difference in LPFS at 2 years of 15% (95% CI 6-26; 76% EIA plus regional hyperthermia vs 61% EIA). For disease-free survival the relative hazard was 0.70 (95% CI 0.54-0.92, p=0.011) for EIA plus regional hyperthermia compared with EIA alone. The treatment response rate in the group that received regional hyperthermia was 28.8%, compared with 12.7% in the group who received chemotherapy alone (p=0.002). In a pre-specified per-protocol analysis of patients who completed EIA plus regional hyperthermia induction therapy compared with those who completed EIA alone, overall survival was better in the combined therapy group (HR 0.66, 95% CI 0.45-0.98, p=0.038). Leucopenia (grade 3 or 4) was more frequent in the EIA plus regional hyperthermia group compared with the EIA-alone group (128 of 165 vs 106 of 167, p=0.005). Hyperthermia-related adverse events were pain, bolus pressure, and skin burn, which were mild to moderate in 66 (40.5%), 43 (26.4%), and 29 patients (17.8%), and severe in seven (4.3%), eight (4.9%), and one patient (0.6%), respectively. Two deaths were attributable to treatment in the combined treatment group, and one death was attributable to treatment in the EIA-alone group. To our knowledge, this is the first randomised phase 3 trial to show that regional hyperthermia increases the benefit of chemotherapy. Adding regional hyperthermia to chemotherapy is a new effective treatment strategy for patients with high-risk STS, including STS with an abdominal or retroperitoneal location. Deutsche Krebshilfe, Helmholtz Association (HGF), European Organisation of Research and Treatment of Cancer (EORTC), European Society for Hyperthermic Oncology (ESHO), and US National Institute of Health (NIH).

European Organisation of Research and Treatment of Cancer (EORTC) Gastrointestinal Group: Workshop on the role of metabolic imaging in the neoadjuvant treatment of gastrointestinal cancer

Metabolic imaging and early response assessment by positron emission tomography (PET) are gaining importance in guiding treatment of localised and metastatic gastrointestinal tumours. During a workshop organised by the European Organisation of Research and Treatment of Cancer (EORTC) Gastrointestinal Tract Cancer Group the most relevant research questions, methodological aspects and unmet clinical needs in this disease were discussed. Potential future trials were drafted. This paper reviews the lectures and discussions held during this workshop and summarises the action points for the further investigation of metabolic imaging to guide treatment in gastrointestinal tumours.

Sentinel node biopsy in breast cancer: technique and indication

Sentinel node biopsy (SNB) has proved to be a useful and accurate procedure for lymph node staging in breast cancer and melanoma and should be standard of care in the treatment of these tumors. In other malignancies (colon, rectum, stomach, esophagus, head and neck and thyroid, cervix uteri) it is still under investigation. SNB in breast cancer was accepted as a sole and reliable diagnostic method in breast cancer by the panel of distinguished experts at the 8th international conference of primary therapy of early breast cancer 2003 in St. Gallen. Combination of the current techniques with radiocolloids and blue dye, applicated superficially (intradermal, subdermal, peri- and subareolar) and deeply (peritumoral, intratumoral, subtumoral) enables high identification rates and negative predictive values. It should be performed by teams consisting of surgeons, pathologists and nuclear medicine specialists with appropriate training and experience. Accepted indications are uni- and multifocal tumors smaller than 3 cm without suspicious findings in the axilla, furthermore SNB is indicated in patients with large ductal carcinoma in situ (>2 cm) and/or with assumed microinvasion. Albeit SNB could be shown to be safe after preoperative chemotherapy and in multicentric breast cancer, due to lack of sufficient data it is still under discussion in these cases. Expedience of this procedure in other lymph node basins, along the mammaria interna vessels or in the infra- and supraclavicular region is considered to be at an investigative stage as well. SNB allows the pathologist to focus on a small number of nodes most likely to contain metastases. Application of serial sectioning and immunohistochemistry results in a more accurate staging than routine examination. Detection of additional micrometastases that are found in 10–15% leads to an upgrading from N0 to N1. Broad application and refurbishment led to scientific discussion of prognostic importance of micrometastases and its relevance regarding axillary dissection and adjuvant systemic treatment. Although many unicentric and multicentric observational studies validated by complete axillary dissection could demonstrate that SNB is accurate and suitable for all operable clinically node-negative breast cancers, long-term results and especially the incidence of axillary recurrence and its sequelae are outstanding. Findings of ongoing large prospective randomized trials like NSABP 32, Z0010 and Z0011 of the American College of Surgeons (ACOSOG), the AMAROS-Trial of the European Organisation of Research and Treatment of Cancer (EORTC) and the ALMANAC-Trial of the British Association of Surgical Oncology (BASO) will give a conclusive answer. Significant improvement in morbidity and quality of life measurements could be revealed several times in unicentric and even in multicentric studies like ALMANAC. Sentinel node biopsy is a team approach, requirements are good cooperation and well-defined structures of quality indicators and documentation. Participation in national clinical studies is recommended.