Vassilios Vassiliou

International field testing of the reliability and validity of the EORTC QLQ‐BM22 module to assess health‐related quality of life in patients with bone metastases

The objective of this international field study was to test the reliability, validity, and responsiveness of the European Organization for Research and Treatment of Cancer (EORTC) QLQ‐BM22 module to assess health‐related quality of life (HRQOL) in patients with bone metastases.

Quality of Life After Palliative Radiation Therapy for Patients With Painful Bone Metastases: Results of an International Study Validating the EORTC QLQ-BM22

PURPOSE Radiation therapy (RT) is an effective method of palliating painful bone metastases and can improve function and reduce analgesic requirements. In advanced cancer patients, quality of life (QOL) is the primary outcome of interest over traditional endpoints such as survival. The purpose of our study was to compare bone metastasis-specific QOL scores among patients who responded differently to palliative RT. METHODS AND MATERIALS Patients receiving RT for bone metastases across 6 countries were prospectively enrolled from March 2010-January 2011 in a trial validating the QLQ-BM22 and completed the QLQ-BM22 and the core measure (QLQ-C30) at baseline and after 1 month. Pain scores and analgesic intake were recorded, and response to RT was determined according to the latest published guidelines. The Kruskal-Wallis nonparametric and Wilcoxon rank sum tests compared changes in QOL among response groups. A Bonferroni-adjusted P<.003 indicated statistical significance. RESULTS Of 79 patients who received palliative RT, 59 were assessable. Partial response, pain progression, and indeterminate response were observed in 22, 8, and 29 patients, respectively; there were no patients with a complete response. Patients across all groups had similar baseline QOL scores apart from physical functioning (patients who progressed had better initial functioning). One month after RT, patients who responded had significant improvements in 3 of 4 QLQ-BM22 domains (painful site, P<.0001; painful characteristic, P<.0001; and functional interference, P<.0001) and 3 QLQ-C30 domains (physical functioning, P=.0006; role functioning, P=.0026; and pain, P<.0001). Patients with progression in pain had significantly worse functional interference (P=.0007) and pain (P=.0019). CONCLUSIONS Patients who report pain relief after palliative RT also have better QOL with respect to bone metastasis-specific issues. The QLQ-BM22 and QLQ-C30 are able to discriminate among patients with varying responses and are recommended for use in future bone metastasis clinical trials.

A novel study investigating the therapeutic outcome of patients with lytic, mixed and sclerotic bone metastases treated with combined radiotherapy and ibandronate

PurposeTo investigate the therapeutic response of patients with different types of bone metastases treated with combined radiotherapy and bisphosphonates.Patients and methodsBy using computed tomography 52 patients were grouped into groups of lytic, mixed and sclerotic bone lesions. All patients were treated with concomitant radiotherapy and ibandronate (10 monthly cycles) and underwent clinical and radiological evaluations prior to therapy and at 3, 6 and 10 months of follow up.ResultsAt baseline there were statistically significant differences between the three groups for all the evaluated parameters. From 3 months onwards differences were leveled out. Statistically significant improvements were noted at all time points of evaluation for all groups in parameters such as pain (0–10), quality of life (QOL-physical functioning, 0–100) and Karnofsky performance status (KPS). The average pain score for the lytic group was reduced from 8.1 to 1.5 points at 3 months. The corresponding reductions for the mixed and sclerotic groups were from 6.2 to 0.5 and from 4.4 to 0.3 points respectively. Complete pain responses were >76.4% at all time points for all groups. Opioid consumption was also markedly reduced. Overall, the highest clinical response was noted for the lytic group, even though the mean values of pain, QOL and KPS were worse than those of the two other groups at all time points (apart from pain score at 10 months). The percentage of patients of the lytic group experiencing a complete pain response was the least of the three groups during follow up. At 10 months bone density was almost tripled for the lytic and almost doubled for the mixed group.ConclusionsEven though the therapeutic outcome for the three groups was similar, the degree of clinical response and reossification differed.

Predictive factors for overall quality of life in patients with advanced cancer

ObjectiveThis study examined which domains/symptoms from the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 15 Palliative (QLQ-C15-PAL), an abbreviated version of the health-related EORTC QLQ-C30 questionnaire designed for palliative cancer patients, were predictive of overall quality of life (QOL) in advanced cancer patients.MethodsPatients with advanced cancer from six countries completed the QLQ-C15-PAL at consultation and at one follow-up point. Univariate and multivariate regression analyses were conducted to determine the predictive value of the EORTC QLQ-C15-PAL functional/symptom scores for global QOL (question 15).ResultsThree hundred forty-nine patients completed the EORTC QLQ-C15-PAL at baseline. In the total patient sample, worse emotional functioning, pain, and appetite loss were the most significant predictive factors for worse QOL. In the subgroup of patients with bone metastases (n = 240), the domains mentioned above were also the most significant predictors, whereas in patients with brain metastases (n = 109), worse physical and emotional functioning most significantly predicted worse QOL. One-month follow-up in 267 patients revealed that the significant predictors changed somewhat over time. For example, in the total patient sample, physical functioning, fatigue, and appetite loss were significant predictors at the follow-up point. A sub-analysis of predictive factors affecting QOL by primary cancer (lung, breast, and prostate) was also conducted for the total patient sample.ConclusionDeterioration of certain EORTC QLQ-C15-PAL functional/symptom scores significantly contributes to worse overall QOL. Special attention should be directed to managing factors most influential on overall QOL to ensure optimal management of advanced cancer patients.

Bone Metastases: Assessment of Therapeutic Response through Radiological and Nuclear Medicine Imaging Modalities

Radiological and nuclear medicine imaging modalities used for assessing bone metastases treatment response include plain and digitalised radiography (XR), skeletal scintigraphy (SS), dual-energy X-ray absorptiometry (DEXA), computed tomography (CT), magnetic resonance imaging (MRI), [(18)F] fluorodeoxyglucose positron emission tomography (FDG-PET) and PET/CT. Here we discuss the advantages and disadvantages of these assessment modalities as evident through different clinical trials. Additionally, we present the more established response criteria of the International Union Against Cancer and the World Health Organization and compare them with newer MD Anderson criteria. Even though serial XR and SS have been used to assess the therapeutic response for decades, several months are required before changes are evident. Newer techniques, such as MRI or PET, may allow an earlier evaluation of response that may be quantified through monitoring changes in signal intensity and standard uptake value, respectively. Moreover, the application of PET/CT, which can follow both morphological and metabolic changes, has yielded interesting and promising results that give a new insight into the natural history of metastatic bone disease. However, only a few studies have investigated the application of these newer techniques and further clinical trials are needed to corroborate their promising results and establish the most suitable imaging parameters and evaluation time points. Last, but not least, there is an absolute need to adopt uniform response criteria for bone metastases through an international consensus in order to better assess treatment response in terms of accuracy and objectivity.

International validation of the EORTC QLQ-ELD14 questionnaire for assessment of health-related quality of life elderly patients with cancer

Background:Older people represent the majority of cancer patients but their specific needs are often ignored in the development of health-related quality of life (HRQOL) instruments. The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-ELD15 was developed to supplement the EORTC’s core questionnaire, the QLQ-C30, for measuring HRQOL in patients aged >70 years in oncology studies.Methods:Patients (n=518) from 10 countries completed the QLQ-C30, QLQ-ELD15 and a debriefing interview. Eighty two clinically stable patients repeated the questionnaires 1 week later (test–retest analysis) and 107 others, with an expected change in clinical status, repeated the questionnaires 3 months later (response to change analysis, RCA).Results:Information from the debriefing interview, factor analysis and item response theory analysis resulted in the removal of one item (QLQ-ELD15QLQ-ELD14) and revision of the proposed scale structure to five scales (mobility, worries about others, future worries, maintaining purpose and illness burden) and two single items (joint stiffness and family support). Convergent validity was good. In known-group comparisons, the QLQ-ELD14 differentiated between patients with different disease stage, treatment intention, number of comorbidities, performance status and geriatric screening scores. Test–retest and RCA analyses were equivocal.Conclusion:The QLQ-ELD14 is a validated HRQOL questionnaire for cancer patients aged ⩾70 years. Changes in elderly patients’ self-reported HRQOL may be related to both cancer evolution and non-clinical events.

Determinants of quality of life in advanced cancer patients with bone metastases undergoing palliative radiation treatment.

PurposeAssessment of health-related quality of life (HRQOL) is critical to effective delivery of palliative care in patients with advanced cancer. The current study analyzes relationships between baseline social determinants of health and medical factors, and self-reported HRQOL in patients with bone metastases receiving palliative radiotherapy.Methods and materialsAdvanced cancer patients referred for radiotherapy treatment of bone metastases completed the EORTC QLQ-C30 questionnaire in multiple outpatient clinics internationally. Demographics and social determinants were collected as baseline information. Univariate and Bonferroni-adjusted multivariate linear regression analyses were used to detect significant correlations between baseline determinants and different HRQOL domains.ResultsKarnofsky Performance Status (KPS) was correlated with better physical (p = 0.0002), role (p < 0.0001), emotional (p < 0.0001), and social (p < 0.0001) functioning, and global health scores (p = 0.0015) and predicted lower symptom scores for fatigue (p < 0.0001), pain (p < 0.0001), appetite loss (p < 0.0001), and constipation (p < 0.0001). Increased age was predictive of better social functioning (p < 0.0001) and less insomnia (p = 0.0036), higher education correlated with better global health status (p = 0.0043), and patients who were employed or retired had improved physical functioning (p = 0.0004 and p = 0.0030, respectively) and less financial challenges compared to patients who were unemployed (p = 0.0005).ConclusionsBaseline KPS had the greatest influence on EORTC QLQ-C30 domain scores. Age, education level, and employment status had significant impacts, although on fewer domains. Further studies that investigate baseline determinants are worthwhile to clarify relationships in order to care for patients more effectively at the end of life.

Expression profiling of 21 biomolecules in locally advanced nasopharyngeal carcinomas of Caucasian patients

BackgroundSince scarce data exist on the pathogenesis of nasopharyngeal carcinoma in Caucasian patients, we attempted to elucidate the responsible molecular pathways in this patient population.MethodsFormalin-fixed paraffin-embedded tumor tissue samples from 107 patients, diagnosed with locally-advanced nasopharyngeal carcinoma and treated with chemotherapy or chemo-radiotherapy, were analyzed by immunohistochemistry for the expression of the following proteins: E-cadherin, P-cadherin, Fascin-1, Cyclin D1, COX-2, EGFR, VEGF-A, VEGF-C, VEGFR-2, VEGFR-3, ERCC1, p53, p63, Ki67, MAPT, phospho-p44/42MAPK, PTEN, phospho-AKT, phospho-mTOR, and phospho-GSK-3β. EBER status was assessed by in situ hybridization. The majority of the cases were included in tissue microarray. All stains were performed and assessed centrally by two pathologists. The median follow-up time was 76.8 (42.3 – 99.2) months.ResultsBiomolecules expressed in >90% of cases were: p53, COX-2, P-cadherin, EBER, phospho-GSK-3β, and Fascin-1. WHO II+III tumors were more frequently EBER & PTEN positive and VEGF-A negative. Advanced age was significantly associated with positive phospho-GSK-3β and ERCC1 expression; male gender with positive phospho-AKT and phospho-p44/42MAPK; and worse performance status (1 or 2) with negative Ki67, ERCC1, PTEN, and phospho-mTOR expression. Earlier disease stage was closely associated with p63, MAPT, PTEN, and Cyclin D1 positivity. Univariate Cox regression analysis highlighted Cyclin D1 as a negative prognostic factor for disease-free survival (p=0.034) and EBER as a positive one for overall survival (p=0.048). In multivariate analysis, advanced age and stage, poor performance status, and positive ERCC1 emerged as predictors of worse disease-free and overall survival, as opposed to positive phospho-mTOR. Clustering analysis defined two protein-expression groups being predictive of better overall survival (p=0.043).ConclusionsOur study is the first to examine the activation and interaction of established biomolecules and signaling pathways in Caucasian NPC patients in an effort to reveal new therapeutic targets.

Osteonecrosis of the Jaws

Background:Bisphosphonate (BP) use has increased dramatically in recent years, becoming an integral part of the overall antineoplastic management of patients with metastatic bone disease. Even though their application has shown to be effective in reducing pain and minimizing the risk of skeletal-related events, their administration may bring also adverse events such osteonecrosis of the jaws (ONJ).Methods:After a thorough review of the literature, important aspects of the pathophysiology, diagnosis, prevention, and treatment of ONJ are presented.Results:ONJ is evident in up to 10% of patients receiving intravenous BP treatment. Despite the fact that its exact pathophysiology is unknown, it is characterized by bone necrosis that can occur either spontaneously or after dental surgery or tooth extraction. Panoramic radiographs are useful for the diagnosis and routine assessment of patients and computed tomography can differentiate between ONJ and metastatic disease. Additionally, magnetic resonance imaging depicts local disease extension readily, and scintigraphy is the most sensitive imaging modality for detecting early involvement. Preventive measures and routine dental evaluations are essential components of the overall patient management. In the event of ONJ, stage I or II should be managed conservatively, whereas more advanced stages (III and IV) should be treated surgically.Conclusion:ONJ is a well-defined clinical entity that all medical and dental doctors should be aware of, since if it is not dealt with readily and effectively, it may deteriorate the clinical status and quality of life of affected patients.Hintergrund:Bisphosphonate haben sich in den letzten Jahren als ein integraler Bestandteil der multimodalen Therapie von Patienten mit Knochenmetastasen etabliert. Ihr erfolgreicher Einsatz in der Schmerzreduktion ossärer Läsionen sowie der Prävention skelettaler Komplikationen steht jedoch auch in Assoziation zu Osteonekrosen des Kiefers (ONJ [„osteonecrosis of the jaw“]).Methodik:In einem Übersichtsartikel werden die relevanten Aspekte der Pathophysiologie, Diagnostik, Prävention und Behandlung von ONJ erläutert.Ergebnisse:Ätiologie und Pathogenese sind nicht hinreichend geklärt, und ONJ unter Bisphosphonatbehandlung können entweder spontan oder nach Zahnextraktion bzw. kieferchirurgischen Eingriffen auftreten. Die Orthopantomographie ist die diagnostische Routinemodalität, wobei Computertomographie und Magnetresonanztomographie für die Differenzierung gegenüber Metastasen und zur Erfassung des Krankheitsausmaßes von Bedeutung sind. Die Knochenszintigraphie hat die höchste Sensitivität in der Früherkennung von ONJ, wobei sorgfältige Nachsorge und engmaschige zahnärztliche Kontrolle wichtige Präventionsmaßnahmen sind. Die Behandlung von ONJ sollte in den Stadien I und II konservativ, in den höhergradigen Stadien (III und IV) operativ erfolgen.Schlussfolgerung:ONJ stellen eine schwerwiegende Komplikation mit dem Risiko einer deutlichen Einschränkung der Lebensqualität dar. Eine engmaschige Patientennachsorge ist für eine frühzeitige und effektive Behandlung von elementarer Bedeutung.

International Patterns of Practice in the Management of Radiation Therapy-induced Nausea and Vomiting

PURPOSE To investigate international patterns of practice in the management of radiation therapy-induced nausea and vomiting (RINV). METHODS AND MATERIALS Oncologists prescribing radiation therapy in the United States, Canada, The Netherlands, Australia, New Zealand, Spain, Italy, France, Hong Kong, Singapore, Cyprus, and Israel completed a Web-based survey that was based on 6 radiation therapy-only clinical cases modeled after the minimal-, low-, moderate-, and high-emetic risk levels defined in the antiemetic guidelines of the American Society of Clinical Oncology and the Multinational Association of Supportive Care in Cancer. For each case, respondents estimated the risks of nausea and vomiting separately and committed to an initial management approach. RESULTS In total, 1022 responses were received. Risk estimates and management decisions for the minimal- and high-risk cases varied little and were in line with guideline standards, whereas those for the low- and moderate-risk cases varied greatly. The most common initial management strategies were as follows: rescue therapy for a minimal-risk case (63% of respondents), 2 low-risk cases (56% and 80%), and 1 moderate-risk case (66%); and prophylactic therapy for a second moderate-risk case (75%) and a high-risk case (95%). The serotonin (5-HT)₃ receptor antagonists were the most commonly recommended prophylactic agents. On multivariate analysis, factors predictive of a decision for prophylactic or rescue therapy were risk estimates of nausea and vomiting, awareness of the American Society of Clinical Oncology antiemetic guideline, and European Society for Therapeutic Radiology and Oncology membership. CONCLUSIONS Risk estimates and management strategies for RINV varied, especially for low- and moderate-risk radiation therapy cases. Radiation therapy-induced nausea and vomiting are under-studied treatment sequelae. New observational and translational studies are needed to allow for individual patient risk assessment and to refine antiemetic guideline management recommendations.