Are neurologic symptoms associated with worse QoL in non-CNS cancer patients?

BACKGROUND: The burden of having neurologic symptoms (NS) in cancer patients has scantly been studied; therefore, we performed a study whose purpose was to measure the impact of having clinically active (NS) on the quality of life (QoL) of non-primary CNS cancer patients. METHODS: Patients with systemic cancer (non-primary CNS cancer) sent for neurological evaluation at a single cancer center (INCAN) were prospectively invited to respond the EORTC-QLQ-C30 and BN20 questionnaires. Associations of the questionnairés items were blindly measured for the following groups: NS+ or not (NS-) and having active cancer (AC+) or not (AC-). RESULTS: Of 205 patients aged 55.4 ± 15.4 years, 122 (60%) had NS+ and 107 (52%) AC +. The NS+ group (compared with the NS-) showed a significant worse perception in the following scales/items of the EORTC QLQ-C30: physical functioning (median 86 vs. 92, P = 0.012), role functioning (66 vs. 100, P < 0.001), emotional functioning (75 vs. 83, P = 0.005), cognitive functioning (66 vs. 83, P < 0.001), fatigue (33 vs. 22, P < 0.001), nausea and vomiting (P = 0.021), pain (33 vs. 16, P < 0.001), insomnia (33 vs. 0, P = 0.011), appetite loss (P = 0.021), and global health (66 vs. 75, P = 0.001). CONCLUSION: In patients with systemic (non-CNS) cancer, the QoL is significantly worse for patients with active neurologic symptoms.

Whole Brain Irradiation or Stereotactic RadioSurgery for five or more brain metastases (WHOBI-STER): A prospective comparative study of neurocognitive outcomes, level of autonomy in daily activities and quality of life.

AIMS: To evaluate neurocognitive performance, daily activity and quality of life (QoL), other than usual oncologic outcomes, among patients with brain metastasis ≥5 (MBM) from solid tumors treated with Stereotactic Brain Irradiation (SBI) or Whole Brain Irradiation (WBI). METHODS: This multicentric randomized controlled trial will involve the enrollment of 100 patients (50 for each arm) with MBM ≥ 5, age ≥ 18 years, Karnofsky Performance Status (KPS) ≥ 70, life expectancy > 3 months, known primary tumor, with controlled or controllable extracranial disease, baseline Montreal Cognitive Assessment (MoCA) score ≥ 20/30, Barthel Activities of Daily Living score ≥ 90/100, to be submitted to SBI by LINAC with monoisocentric technique and non-coplanar arcs (experimental arm) or to WBI (control arm). The primary endpoints are neurocognitive performance, QoL and autonomy in daily-life activities variations, the first one assessed by MoCa Score and Hopkins Verbal Learning Test-Revised, the second one through the EORTC QLQ-C15-PAL and QLQ-BN-20 questionnaires, the third one through the Barthel Index, respectively. The secondary endpoints are time to intracranial failure, overall survival, retreatment rate, acute and late toxicities, changing of KPS. It will be considered significant a statistical difference of at least 30% between the two arms (statistical power of 80% with a significance level of 95%). DISCUSSION: Several studies debate what is the decisive factor accountable for the development of neurocognitive decay among patients undergoing brain irradiation for MBM: radiation effect on clinically healthy brain tissue or intracranial tumor burden? The answer to this question may come from the recent technological advancement that allows, in a context of a significant time saving, improved patient comfort and minimizing radiation dose to off-target brain, a selective treatment of MBM simultaneously, otherwise attackable only by WBI. The achievement of a local control rate comparable to that obtained with WBI remains the fundamental prerequisite. TRIAL REGISTRATION: NCT number: NCT04891471.

A Prospective Study on Health-Related Quality of Life and Patient-Reported Outcomes in Adult Brain Tumor Patients Treated with Pencil Beam Scanning Proton Therapy.

Proton therapy (PT) is delivered to complex brain tumors to obtain an optimal curative treatment with limited toxicity. Value-based oncological medicine is increasingly important, particularly when long-term survival is to be expected. This study aims to evaluate health-related quality of life (HRQOL) and patient reported outcomes (PROs) in patients treated with PT for brain tumors. Adult patients with brain tumors treated with PT filled out the EORTC-QLQ-C30 and BN20 questionnaires up to three years following PT. Toxicity was scored using the CTCAE v4.03. QoL and PRO were correlated to clinical factors. Three-year overall survival, distant brain control and local control rates were 98%, 97% and 84%, respectively. No ≥G3 acute toxicity was observed. Late PT-related ≥G3 severe toxicity occurred in seven patients (5.7%). Lower global QoL scores after PT were significantly correlated to low Karnofsky performance status (KPS) before PT (p = 0.001), surgical complications before PT (p = 0.04) and progressive disease (p = 0.017). A low QLQ-30 summary score at one year follow-up was correlated to sex (p = 0.015), low KPS before PT (p < 0.001), and central nervous system symptoms before PT (p = 0.018). Reported QLQ-BN20 neurological symptoms were correlated to lower KPS at baseline (p < 0.001) and surgical complications before PT (p = 0.03). PT-related toxicity only influenced reported symptoms directly following PT, but not QoL. Although global QoL temporarily decreased after treatment, it improved again from one year onwards. Global QoL and reported symptoms over time were not correlated with the proton therapy and were more related to preexisting symptoms and progressive disease. This study assists in improving patient support in patients with brain tumors receiving PT.

Symptom clusters in newly diagnosed glioma patients: which symptom clusters are independently associated with functioning and global health status?

BACKGROUND: Symptom management in glioma patients remains challenging, as patients suffer from various concurrently occurring symptoms. This study aimed to identify symptom clusters and examine the association between these symptom clusters and patients' functioning. METHODS: Data of the CODAGLIO project was used, including individual patient data from previously published international randomized controlled trials (RCTs) in glioma patients. Symptom prevalence and level of functioning were assessed with European Organisation for Research and Treatment of Cancer (EORTC) quality of life QLQ-C30 and QLQ-BN20 self-report questionnaires. Associations between symptoms were examined with Spearman correlation coefficients and partial correlation networks. Hierarchical cluster analyses were performed to identify symptom clusters. Multivariable regression analyses were performed to determine independent associations between the symptom clusters and functioning, adjusted for possible confounders. RESULTS: Included in the analysis were 4307 newly diagnosed glioma patients from 11 RCTs who completed the EORTC questionnaires before randomization. Many patients (44%) suffered from 5-10 symptoms simultaneously. Four symptom clusters were identified: a motor cluster, a fatigue cluster, a pain cluster, and a gastrointestinal/seizures/bladder control cluster. Having symptoms in the motor cluster was associated with decreased (≥10 points difference) physical, role, and social functioning (betas ranged from -11.3 to -15.9, all P < 0.001), independent of other factors. Similarly, having symptoms in the fatigue cluster was found to negatively influence role functioning (beta of -12.3, P < 0.001), independent of other factors. CONCLUSIONS: Two symptom clusters, the fatigue and motor cluster, were frequently affected in glioma patients and were found to independently have a negative association with certain aspects of patients' functioning as measured with a self-report questionnaire.

Validation of the Chinese version of EORTC QLQ-BN20 for patients with brain cancer.

This is a single centre study in mainland China aiming to evaluate the reliability, validity and responsiveness of the Chinese version of EORTC QLQ-BN20, designed by The European Organization for Research and Treatment of Cancer Quality of Life Group to evaluate the life quality of patients with brain tumour, cancer or metastases. One hundred and eighty-eight patients with primary or secondary brain cancer from Hunan Provincial Tumor Hospital during September 2013 to June 2014 completed the Chinese EORTC QLQ-C30/BN20 questionnaires developed by translation, back translation and cultural adaptation. Results were statistically analysed using SPSS17.0. The internal consistency (Cronbach's α coefficient) was between .753 and .869, the correlation coefficients among items and its own dimension were bigger than .4, and all items had a better correlation with its own dimension. The Spearman was used to analyse the correlation of each dimension between EORTC QLQ-BN20 and EORTC QLQ-C30, and the result showed that individual dimensions were moderately correlated, other dimensions were weakly correlated. In conclusion, the Chinese version of EORTC QLQ BN20 questionnaire had great relevance, reliability, convergent validity and discriminant validity. It provides a valuable tool for the assessment of health-related quality of life in clinical studies of Chinese patients with primary or secondary brain cancer.

Trans sodium crocetinate with temozolomide and radiation therapy for glioblastoma multiforme.

OBJECTIVE A new drug, trans sodium crocetinate (TSC), has been developed to enhance the delivery of oxygen to hypoxic tissues. Cancerous tumors, such as glioblastoma multiforme (GBM), are very hypoxic, and it has been suggested that radiation therapy (RT) is more beneficial if tumors are better oxygenated. A Phase I/II clinical trial was conducted to determine the effect of adding TSC to RT sessions. METHODS An open, single-arm clinical trial incorporating the standard of care (SOC) for GBM was conducted at 18 clinical sites. There were 6 weeks of RT consisting of 2 Gy/day for 5 days/week, beginning after an initial resection or stereotactic biopsy to confirm GBM. Temozolomide (TMZ), 75 mg/m2, was given before each RT session. The TSC, 0.25 mg/kg, was intravenously administered around 45 minutes before an RT session 3 days/week, usually on Monday, Wednesday, and Friday. A Phase I run-in period included 2 cohorts. The first cohort contained 3 patients who were given a half dose of the intravenous TSC (that is, 0.25 mg/kg, 3 times per week for only the first 3 weeks of RT). After a Safety Monitoring Committee (SMC) had verified that no dose-limiting toxicity (DLT) had occurred, a second cohort of 6 patients was given the same dosage of TSC but for the full 6 weeks of RT. After the SMC verified that no DLTs had occurred, Phase II began, with the administration of the full 18 doses of TSC. Fifty additional patients were enrolled during Phase II. Following the completion of RT, the patients rested for a month. After that, SOC TMZ chemotherapy (150-200 mg/m2) was administered for 5 days of the 1st week of 6 monthly cycles. No TSC was administered during this chemotherapy phase or later in the trial. Any other follow-up therapies were administered at the discretion of the individual investigators. RESULTS Kaplan-Meier analysis showed that 36% of the full-dose TSC patients were alive at 2 years, compared with historical survival values ranging from 27% to 30% for the SOC. Survival for the biopsy-only subset of patients was 40%, as compared with 42.9% for those patients having a complete resection before treatment. In addition, 2 of the 3 Phase I, Cohort 1 patients survived at 2 years. Contrast MRI data suggested that considerable pseudoprogression had occurred. Both Karnofsky Performance Status (KPS) scores and quality of life (QOL) questionnaires indicated that a good quality of life existed for most patients throughout the trial. No serious adverse events occurring in the trial were attributed to TSC. CONCLUSIONS This trial contained a single arm consisting of 59 patients. The results strongly suggested that adding TSC during RT is beneficial for the treatment of GBM. Trans sodium crocetinate offers a novel, easily implemented way to combat hypoxia in tumor tissue. Clinical trial registration no.: NCT01465347 ( clinicaltrials.gov ).

Evaluation of neuropsychological outcome and "quality of life" after glioma surgery.

PURPOSE: Extended tumour resection is imperative to improve the outcome of glioma patients but also carries the risk of increasing morbidity and thus, potentially, of decreasing the patient's quality of life (QOL). In this pilot study, we evaluated how postoperative neurological and neuropsychological alterations impacted on QOL in patients who underwent glioma resection. METHODS: Twenty-two patients were included in this study and tested at three different time points, i.e. 1 day before surgery (t1), on the day of discharge (t2) and 3 months following surgery (T3). National Institutes of Health Stroke Scale (NIHSS) score, Addenbrook's Cognitive Examination-Revised (ACE-R) and a comprehensive battery of established tests were used to assess neurological and neuropsychological profiles. QOL and subjectively experienced health condition were ascertained through the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC-QLQ C30) and EORTC-QLQ BN20 questionnaires. RESULTS: Postoperatively, 5/22 patients worsened and 5/22 patients improved neurologically. Depending on the neuropsychological test, up to 57.1 % of patients experienced deterioration of some sort of neuropsychological function. Most of these functions, however, recovered during the extended observation period (3 months). There was no correlation between QOL and a patient's neurological or neuropsychological condition. CONCLUSIONS: Our study suggests that extended tumour resection is not necessarily linked to a loss in QOL.