Treatment-associated Symptoms Research Articles

Abstract 4832: The impact of neighborhood-level disadvantage on the patient-reported outcomes of primary brain tumor patients

Abstract There is increased recognition that social determinants of health may impact well-being and health in those with various cancers, but they have not been systematically evaluated in primary brain tumor (PBT) patients. Here, we examined the association between Area Deprivation Index (ADI), a measurement of sociodemographic neighborhood disadvantage, and patient-reported outcomes (PROs) in a cohort of adult PBT patients enrolled in a large National Institutes of Health observational trial (NHS, NCT02851706, PI: Armstrong). We utilized linear regression to assess the relationship between ADI (less advantaged [ADI≥40, n=153, 24%], more advantaged [ADI<40, n=490, 76%]) and patient symptom burden (MDASI-BT), anxiety, and depression (PROMIS Short Forms v1.0 8a). Logistic regression was used to evaluate the association between ADI and health-related quality of life using the 5 dimensions of the EQ-5D-3L. Models were adjusted for age, sex, race/ethnicity, tumor grade, Karnofsky Performance Score (KPS), and tumor recurrence. A sub-analysis stratifying by tumor grade (low, high) was completed. Among 643 PBT patients, the majority resided in more advantaged areas (n=490; 76%) and had high-grade tumors (n=448; 70%). Those who were less advantaged reported more symptom severity (β=1.10, SE=1.05, P=0.041), more activity-related interference (β=1.11, SE=1.05, P=0.03), and had 4.68 times the odds of having moderate-severe difficulty completing self-care tasks (95% confidence interval [1.46, 14.96], P=0.009) compared to those who were more advantaged. KPS was a significant predictor for all three outcomes, and age at diagnosis was significant for PBT symptom severity. Among patients with low-grade tumors, those who were less advantaged reported higher symptom interference (β=1.24, SE=1.10, P=0.020), affective symptoms (β=1.24, SE=1.08, P=0.007), treatment-related symptoms (β=1.21, SE=1.08, P=0.021), general disease symptoms (β=1.26, SE=1.10, P=0.016), activity-related interference (β=1.26, SE=1.09, P=0.006), mood-related interference (β=1.20, SE=1.09, P=0.039), and anxiety (β=1.03, SE=1.02, P=0.023), with KPS being a significant predictor for all outcomes except anxiety. Overall, less advantaged PBT patients reported worse symptom severity and activity-related interference, and those with low-grade tumors experienced more affective symptoms, including fatigue, general disease and treatment-associated symptoms, and symptoms of anxiety, but not neurologic or cognitive symptoms. Living in less advantaged areas may lead to barriers to care access, symptom management medications, or other neighborhood resources that could alleviate PBT patient symptom burden but may compound over time for those with poor performance status or low-grade tumors. These results highlight the need for targeted supportive interventions for PBT patients living in less advantaged areas. Citation Format: Zuena A. Karim, Kimberly Reinhart, Orieta Celiku, Yeonju Kim, Hope Miller, Elizabeth Vera, Jacqueline B. Vo, Terri S. Armstrong, Macy L. Stockdill. The impact of neighborhood-level disadvantage on the patient-reported outcomes of primary brain tumor patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4832.

Trajectories of immune-related serum proteins and quality of life in patients with pancreatic and other periampullary cancer: the CHAMP study

BackgroundThere is still a profound lack of efficient therapeutic strategies against pancreatic and other periampullary adenocarcinoma. Surgery is seldom possible, leaving palliative chemotherapy the only option for most patients. Chemotherapy treatment is however often accompanied by serious side-effects, and the identification of biomarkers for early prediction of disease and treatment-associated symptoms could help alleviate patient suffering. This study investigated the dynamic interrelationship between immune-related serum proteins, routine biomarkers, and health-related quality of life (HRQoL) factors during chemotherapy treatment of patients enrolled in the prospective, observational study Chemotherapy, Host response And Molecular dynamics in Periampullary cancer (CHAMP).MethodsProximity extension assay was applied to analyse 92 immune-associated proteins in longitudinal serum samples from 75 patients, 18 treated with curative and 57 with palliative intent. HRQoL data were available from all patients at baseline (BL), from 41 patients at three months, and from 23 patients at six months. Information on routine laboratory parameters albumin, CA19-9, CEA and CRP were collected from medical charts.ResultsIn total nine proteins; chemokine (C–C motif) ligand 23 (CCL23), cluster of differentiation 4 (CD4), cluster of differentiation 28 (CD28), decorin (DCN), galectin-1 (Gal-1), granzyme B (GZMB), granzyme H (GZMH), matrix metallopeptidase 7 (MMP7), and monocyte chemotactic protein-1 (MCP-1) were strongly correlated (Spearman’s Rho ≤ -0.6 or ≥ 0.6) with either cognitive functioning (DCN), emotional functioning (DCN, MCP-1), dyspnoea (CD28, GZMB, GZMH) or insomnia (CCL23, CD4, Gal-1, MMP7) during treatment. Associations between routine laboratory parameters (CA 19–9, CA-125, CRP, CEA and albumin) and HRQoL factors were overall weaker. None of the investigated proteins were associated with pain.ConclusionsThis is, to our knowledge, the first study exploring associations between serum biomarkers and HRQoL in patients with pancreatic or other periampullary cancer, and some findings merit further validation. The associations of DCN and MCP-1with impaired cognitive and/or emotional functioning are of particular interest, given their established link to various neurodegenerative conditions. Chemotherapy is known to cause persistent cognitive dysfunction with effects on memory and executive function, referred to as “chemo brain”. It would therefore be of great value to identify biomarkers for early detection and management of this debilitating condition.Trial registrationClinical Trial Registration: NCT03724994.

Feasibility of Symptom Monitoring During the First Year of Endocrine Therapy for Early Breast Cancer Using Patient-Reported Outcomes Collected via Smartphone App.

Treatment-associated symptoms drive early discontinuation of adjuvant endocrine therapy (ET) for breast cancer. We hypothesized that symptom monitoring with electronic patient-reported outcomes (ePROs) during adjuvant ET will enhance symptom detection, symptom management, and persistence. Eligible patients were initiating ET for stage 0-III breast cancer. Participants completed ePRO surveys via smartphone at baseline and 1, 3, 6, and 12 months. Measures included Patient-Reported Outcomes Measurement Information System Anxiety, Depression, Fatigue, and Vaginal Discomfort; plus Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events items assessing joint pain, hot flashes, vaginal dryness, concentration problems, and memory problems. Scores surpassing prespecified thresholds triggered alerts, and recommended symptom management pathways were provided to clinicians. The primary objective was to evaluate feasibility, assessed by survey completion rates, with targets of >65% for the baseline survey and ≥1 follow-up survey during the first 6 months. Secondary objectives included 12-month ET discontinuation rate (target: ≤15%), describing symptoms and evaluating pathway implementation. Among 250 participants, 73.2% completed the baseline survey and 69.6% completed ≥1 follow-up survey during the first 6 months. Thirty-one percent of participants had ≥1 symptom alert at baseline and 74% had ≥1 symptom alert during follow-up. The proportions of participants for whom pathway-concordant symptom management was documented at each time point ranged from 12.8% to 36.6%. Twenty-eight participants (11.2%) discontinued ET by 12 months. Symptom monitoring with ePROs during adjuvant ET is feasible. Despite infrequent documentation of pathway-concordant symptom management after symptom alerts, ePROs were associated with favorable short-term ET persistence.

JS01.5.A PHASE 2 TRIAL OF CARBOPLATIN AND BEVACIZUMAB FOR RECURRENT ADULT EPENDYMOMA. A CERN STUDY

Abstract BACKGROUND Most adults with ependymoma undergo tumor resection at the time of diagnosis, which may be followed by radiation. At recurrence, re-resection and/or (re)-irradiation may be given, however, there are few established chemotherapy treatments. A previous retrospective report of 8 patients treated with carboplatin and bevacizumab showed a high response rate with 6 patients demonstrating an imaging response (Green, Neurology 2009). We sought to further investigate this regimen with a prospective trial. MATERIAL AND METHODS We performed a prospective phase 2 study in the CERN Adult Clinical Trials Network. Adult patients with recurrent or progressive ependymoma were enrolled to receive carboplatin (AUC =4-5) every 4 weeks for up to 6 cycles and bevacizumab at 10mg/kg every 2 weeks for one year, with the option to continue until progression or toxicity. The primary endpoint was 12-month PFS rate and >50% defined efficacy. Serial symptom burden measurement at baseline and at the time of disease evaluation using MD Anderson Symptom Inventory-brain tumor (MDASI-BT) or MDASI-Spine patient-reported outcomes (PROs) were used to evaluate the clinical impact of PFS. RESULTS A total of 22 patients with median age of 45 years were accrued and treated; 11 were women. WHO grade was 3 in 13 patients and grade 2 in 9 patients (3 with myxopapillary ependymoma) Ten patients had only spinal cord disease, 3 had both spinal cord and brain involvement and 9 patients had brain involvement alone (6 supratentorial, 3 infratentorial). Previous treatments included radiotherapy in all 22 patients and alkylating chemotherapy in 9 patients. Treatment was well tolerated with expected myelotoxicities and hypertension. The Kaplan-Meier calculated 12-Month PFS rate was 76.4% (95%CI 52.2%, 89.4%), median PFS = 18 months (95%CI 12.2, +∞). There were 2 partial responses (9.1%). Brain tumor responders (objective response or stable disease) showed reduction while non-responders had an increase in both neurologic and cognitive symptoms but similar report of other symptoms. Spine tumor responders and non-responders both showed worsening disease-related symptoms; autonomic symptoms worsened in responders. Activity related interference worsened for all patients. CONCLUSION This treatment regimen was safe and met the primary efficacy endpoint of 12-month PFS rate. The improvement in disease-related symptoms in brain tumor patients supports that the achieved disease stability was clinically meaningful, but the increased activity-related interference suggests that treatment-associated symptoms may impact work, general activity, and walking ability during treatment. Improvements in spine tumor disease-associated symptoms were not seen. A confirmatory trial is warranted to further investigate the findings and to determine if there are differences in response amongst ependymoma subtypes and tumor location.

Clinical and sociodemographic determinants of disease-specific health-related quality of life in long-term breast cancer survivors

PurposeIt is important to monitor disease-specific health-related quality of life (HRQoL) in breast cancer (BC) survivors to identify potential unmet supportive care needs. However, previous studies were characterized by small samples of mostly short-term survivors and were limited to certain age ranges, stages and/or treatments.MethodsWe used data from 3045 long-term BC survivors (5–15 years post-diagnosis) recruited in a German multi-regional population-based study. We assessed disease-specific HRQoL with the EORTC QLQ-BR23, scoring from 0 to 100. Differences in functioning and symptoms according to age at survey, self-reported treatments, stage, and disease status (disease-free vs. active disease) were assessed with multiple regression. Active disease was defined as any self-report of recurrence, metastasis or second primary cancer after the index cancer.ResultsOlder BC survivors reported a higher body image and a better future perspective, but lower sexual functioning. Survivors aged 30–49 years who had breast-conserving therapy or mastectomy with breast reconstruction reported a better body image compared to those who had mastectomy only. We also found differences in symptoms according to treatments in some age groups. Stage at diagnosis was not associated with HRQoL overall and in most age subgroups. Disease-free BC survivors aged 30–79 years reported a better future perspective and less systemic therapy side effects than those with active disease.ConclusionSeveral treatment-associated symptoms and functioning detriments were found 5–15 years after diagnosis. The results emphasize the need of a comprehensive, individualized survivorship care, recognizing differential needs of long-term BC survivors according to age, treatment modalities, and disease status.

MO395: Physical Function, Muscle Force Production and Physical Activity Levels In Peritoneal Dialysis Patients

Abstract BACKGROUND AND AIMS Chronic kidney disease (CKD) is a highly predominant worldwide disease, representing an enormous economic burden with profound social implications. In addition to frequent infections and mineral and bone disorders, CKD patients also experience exacerbated mobility deficits and severe skeletal muscle wasting, which further contributes to the development of co-morbidities and increased mortality. CKD patients suffering from end-stage renal disease often undergo dialysis treatment, such as peritoneal dialysis (PD), whose treatment-associated symptoms and physical fatigue have been reported to be less noticeable than in haemodialysis patients. In healthy individuals, there is substantial evidence to support the associations between reduced physical activity (PA) levels with a sedentary lifestyle and aggravated bone disorders and muscle wasting. It is conceivable that these associations become exacerbated in CKD patients. Hence, the present preliminary study aims to characterize PD patients in terms of their physical function, muscle force production and daily PA levels. METHOD A total of 18 CKD patients undergoing PD have volunteered to partake in this study (10 males, mean ± SD: age = 55 ± 11 years). Of these 15 have completed physical function testing (Timed Up and Go (TUG), Sit-to-Stand (STS) 5 and, STS 60s) and isometric handgrip strength assessment through handheld dynamometry. Isometric peak force (surrogate of maximum strength), rate of force development (RFD, surrogate of explosive muscle strength) and force-time root mean square (RMS, surrogate of muscle endurance) of the knee extensors, elbow flexors and hip flexors, were also assessed in 12 of these patients using a portable load cell. All participants used tri-axial accelerometers continuously for a week, that were used to estimate PA levels and the number of impacts (movements that expose an individual to accelerations of a certain magnitude). In total, 8 patients have completed all measurements. RESULTS PD patients were able to complete the TUG test in 6.6 ± 0.3s, the STS 5 in 10.8 ± 0.6s and stood 26.8 ± 1.8 times in the STS 60. Participants showed isometric peak forces of 272.9 ± 28.5N (handgrip), 92.6 ± 10.7N (elbow flexion), 93.0 ± 14.3N (hip flexion) and 137.0 ± 33.4N (knee extension). The RFD observed during elbow flexion, hip flexion and knee extension was 92.3 ± 15.3N/s, 104.3 ± 29.7N/s and 144.4 ± 43.4N/s, respectively. RMS of the elbow flexors, hip flexors and knee extensors was 68.8 ± 9.1, 64.7 ± 11.8 and 92.3 ± 21.7, respectively. The accelerometers were used for 7.2 ± 0.2 days (15.7 ± 0.7 h/day) and showed that 94.3 ± 2.8% of impacts experienced by participants were under 0.5 g (over 640 000 impact loadings/day), 0.8 ± 0.3% of observed impacts were between 0.5–1g (>5800 daily impacts), the impact loadings between 1–1.5g accounted for 0.11 ± 0.01% of impact loadings (731 ± 349 impacts/day) and 0.03 ± 0.01% of impact loadings (155 ± 62 impacts/day) were ˃ 1.5g. Participants spent 646.2 ± 59.2 min/day in sedentary behaviour (73.2 ± 3.7% of time), 210.2 ± 30.2 min/day in light PA (25.6 ± 3.5% of time), 7.9 ± 1.9 min/day in moderate PA (1.0 ± 0.2% of time) and just 1.8 ± 1.8 min/day in vigorous PA (0.2 ± 0.2% of time). Lastly, hip flexion peak force and force-time curve RMS were significantly associated with the number of repetitions completed during the STS 60 (r = 0.85 and r = 0.91 respectively, P < 0.05). CONCLUSION Although CKD patients undergoing PD showed apparently healthy physical function, the muscle force production values tend to be on the lower end compared to existing literature. Nonetheless, those with stronger hip flexors had better results in the STS 60 test. It is possible that the disproportionate amount of time spent in sedentary behaviour and low-intensity PA and the very limited exposure to moderate and vigorous impact loadings may be responsible, at least in part, for these exacerbated deficits. FUNDING: Portuguese Foundation of Science and Technology (UID/04045/2020).

Exercise recommendations and referral patterns of oncology professionals.

Exercise physiologists and physiotherapists can provide exercise interventions for cancer survivors; however, many do not access this support. Our primary aim explored referral habits to exercise professionals and attitudes of oncology professionals. Secondary aims explored fitness levels of oncology professionals and the relationship between fitness and exercise referral habits. Oncology professionals (n=67) attending a national cancer conference in Australia participated in this cross-sectional study (23% doctors, 11% nurses, 25% allied health, and 41% other). A subgroup (n=49) completed a fitness assessment measuring aerobic fitness (3-minute step test), muscle strength (handgrip dynamometry), and body composition (waist-to-hip ratio). Oncology professionals in a position to refer patients to exercise professionals were assessed on their history of patient referrals. Sixty-seven of 750 eligible conference delegates participated (9% recruitment rate), of which 73% completed fitness assessments. Participants displayed above average physical activity and fitness levels with 60% meeting exercise guidelines. The majority (92%) agreed that exercise is important among cancer survivors to attenuate treatment-associated symptoms. Most understand the role of exercise physiologists (61%) and physiotherapists (64%) in cancer care. Seventy-three percent reported that referral to exercise professionals is optimal to increase exercise participation. Most (82%) oncology professionals who are able to refer patients to exercise professionals have self-reported doing so, while 91% recommended exercise themselves. Sixty-two percent were aware of evidence-based exercise guidelines. Fitness levels (p=0.25), strength (p=0.88), and physical activity (p=0.33) did not impact referrals made to exercise professionals. There was high awareness exercise-oncology benefits and evidence-based guidelines existed among sampled participants. Oncology professionals understand the role of exercise professionals, reflected by high self-reported referral rates. Implementing referral pathways to exercise professionals in cancer care may facilitate improved patient outcomes.

Long-Term Side Effects of Adjuvant Therapy in Primary Breast Cancer Patients: Results of a Web-Based Survey

Background: Chronic treatment sequelae may substantially reduce the long-term quality of life in breast cancer survivors. Methods: We report a comprehensive Web-based survey on the presence of long-term side effects of adjuvant anti-breast cancer therapy in 1,506 patients who had been diagnosed with primary breast cancer at least 1 year before. Results: Fatigue, depression, depressive mood, concentration deficit, pain, changes of mucosa and skin appendages, as well as symptoms of peripheral neuropathy were the most prevalent reported complaints. Chemotherapies - taxane-based regimens in particular - were associated with increased rates of long-term symptoms, including persistent peripheral neuropathy. Overall, the data show a substantial prevalence of a wide variety of potentially treatment-associated symptoms over a protracted time frame after the diagnosis of breast cancer. The burden of symptoms was high for fatigue, depression, sleep disturbances, pain, and peripheral neuropathic symptoms. Conclusion: Estimating the burden of chronic toxicities should contribute to enhance rational decision-making on treatments including chemotherapy in patients with low versus high risk of recurrence.

PSS63 - IDENTIFYING PATIENT PREFERENCES FOR GLAUCOMA TREATMENT: EVIDENCE FROM LITERATURE REVIEW

One of the main objectives of glaucoma treatment is to lower intraocular pressure through topical medication, laser, or more invasive procedures (surgery, or surgical implants). In addition, long-lasting drug depots may also soon be a treatment option. The aim of current review was to identify the patient preferences towards glaucoma treatment and relevant influencing factors. A comprehensive literature search was performed for studies published in English from inception through August 2017 in Embase, MEDLINE, MEDLINE-In Process, and Cochrane library. Studies reporting patient preferences for any glaucoma treatment were included. The review identified 32 studies (7 RCTs, 1 non-RCTs, 12 observational studies and 7 single-arm studies) including studies assessing treatment-switching (n=11) and factors influencing treatment preference (n=5). Patients receiving monotherapies had significantly higher treatment satisfaction compared to polytherapies (p=0.05). Topical agents (QD regimen) were more convenient compared to BID regimens (p=0.104). Among monotherapies, brimonidine was preferred over topical β-blockers (less efficacious) or dual therapies (less convenient); travoprost BAK-free over latanoprost; and bimatoprost over travoprost. Patients switching from PGA monotherapies or mono/adjunctive therapies were significantly more likely to accept fixed-dose combinations such as travoprost/timolol. Additionally, studies reported high patient willingness to accept a novel glaucoma treatment such as sustained drug delivery (via punctal plug, subconjunctival or intracameral route) and implant (p=0.011) based upon effectiveness and cost. Other factors influencing patient preference were clear center vision, outdoor mobility, travelling distance during follow-ups, and treatment-associated symptoms (vision blurring, drowsiness, or inhibition of sexual performance). No studies assessing surgical treatment options were identified. Evidence clearly indicates that glaucoma patients have preference towards more efficacious and less frequent medication regimens. In addition, patients are willing to accept novel treatment options such as surgical implants and sustained release medication depots. However, scarce evidence necessitates the need for more research focusing on patient preferences towards surgical treatment options.

Evaluation of the Effectiveness of a Multimodal Complementary Medicine Program for Improving the Quality of Life of Cancer Patients during Adjuvant Radiotherapy and/or Chemotherapy or Outpatient Aftercare

Objectives: Evidence for complementary therapies as important strategies to relieve cancer treatment-associated symptoms is increasing. Mostly, these complementary therapies start at the end of adjuvant treatments, resulting in a long delay until the well-being of patients is addressed. Further, long distances between the rehabilitation center and the patients' residence hinder patients' compliance. Methods: The multimodal outpatient LOTUS Care Cure Project (LCCP) was tested in a randomized controlled trial including patients of various cancer entities and stages while on adjuvant chemotherapy and/or radiotherapy or outpatient aftercare. The intervention group received the LCCP additionally to the conventional treatment (LCCP group, n = 50). The control group (CG) was split into 2 groups, with (CG1, n = 33) and without (CG2, n = 17) weekly talks. The primary endpoint was quality of life (QoL) after 3 months. Results: In the LCCP group, QoL significantly improved after 3 months compared to CG2 (p = 0.022) but not compared to CG1. Other parameters showing a significant improvement were cognitive (p < 0.05, vs. CG1 and CG2) and social function (p < 0.05, vs. CG2). Conclusions: This pilot study describes a multimodal outpatient complementary therapy program conducted in parallel with conventional therapies and its potential to significantly improve QoL and reduce treatment-associated side effects. To substantiate these data, multicenter trials are needed.

Randomized Trial of Thymectomy in Myasthenia Gravis

BackgroundThymectomy has been a mainstay in the treatment of myasthenia gravis, but there is no conclusive evidence of its benefit. We conducted a multicenter, randomized trial comparing thymectomy plus prednisone with prednisone alone.MethodsWe compared extended transsternal thymectomy plus alternate-day prednisone with alternate-day prednisone alone. Patients 18 to 65 years of age who had generalized nonthymomatous myasthenia gravis with a disease duration of less than 5 years were included if they had Myasthenia Gravis Foundation of America clinical class II to IV disease (on a scale from I to V, with higher classes indicating more severe disease) and elevated circulating concentrations of acetylcholine-receptor antibody. The primary outcomes were the time-weighted average Quantitative Myasthenia Gravis score (on a scale from 0 to 39, with higher scores indicating more severe disease) over a 3-year period, as assessed by means of blinded rating, and the time-weighted average required dose of prednisone over a 3-year period.ResultsA total of 126 patients underwent randomization between 2006 and 2012 at 36 sites. Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a 3-year period than those who received prednisone alone (6.15 vs. 8.99, P<0.001); patients in the thymectomy group also had a lower average requirement for alternate-day prednisone (32 mg vs. 54 mg, P<0.001). Fewer patients in the thymectomy group than in the prednisone-only group required immunosuppression with azathioprine (17% vs. 48%, P<0.001) or were hospitalized for exacerbations (9% vs. 37%, P<0.001). The number of patients with treatment-associated complications did not differ significantly between groups (P=0.73), but patients in the thymectomy group had fewer treatment-associated symptoms related to immunosuppressive medications (P<0.001) and lower distress levels related to symptoms (P=0.003).ConclusionsThymectomy improved clinical outcomes over a 3-year period in patients with nonthymomatous myasthenia gravis. (Funded by the National Institute of Neurological Disorders and Stroke and others; MGTX ClinicalTrials.gov number, NCT00294658.)

A complementary care program for improving quality of life of cancer patients during adjuvant radiotherapy and/or chemotherapy or outpatient aftercare.

e21697Background: Evidence for complementary therapies (CTs) as important strategies to relieve cancer treatment-associated symptoms and to improve physical and emotional well-being is increasing. ...

PCSM-06COMPARISON OF THE SYMPTOM BURDEN IN ACTIVE TREATMENT VERSUS FOLLOW-UP FOR PRIMARY BRAIN TUMOR PATIENTS

BACKGROUND: Primary Brain Tumor (PBT) patients have unique symptoms compared with patients with systemic cancers, likely related to involvement of the central nervous system. Despite aggressive treatment, declaration of true remission is difficult because of the high rate of recurrence. The purpose of this study was to compare the symptom experience of patients in follow-up with those undergoing active treatment. METHODS: Cross-sectional patient-reported outcome symptom data (M.D. Anderson Symptom Inventory-Brain Tumor) measuring both core oncology and PBT-specific symptoms was collected. Active-treatment and follow-up groups were compared for each of 22 symptom items in terms of symptom severity, number of symptoms and differences in overall severity. Six functional symptom groupings and group differences were assessed with linear regression. FINDINGS: The sample included 488 patients (273 on active treatment; 215 follow-up). The on-treatment group was significantly older [48.83 years (18-79) vs 44.46 years (18-84)] and more likely to have a glioblastoma (p < 0.0001). Mean symptom severity was not significantly different between groups [on-treatment 1.64 (0-7.36), follow-up 1.57 (0-6.36), p = 0.5747]. Patients on treatment reported higher symptom prevalence for 8 of 22 items. They reported more moderate/severe nausea (p = 0.0409) and bowel problems (p = 0.0029), with higher aggregate general symptom (p = 0.0044) and GI symptom (p = 0.0044) scores. After adjusting for age and KPS, the number of symptoms were not different between groups (p = 0.2346), but general (p = 0.0407) and GI (0.0056) symptoms were more severe in those on active treatment. CONCLUSION: This preliminary analysis shows that PBT patients on active treatment have more severe treatment-associated symptoms. However, patients in follow-up have disease-related symptoms, number of symptoms and overall symptom burden as severe as those on treatment. These findings underscore the need for disease-related symptom management for both groups and additional research to determine factors that explain symptom pattern over the course of the disease.

Molecular Genetics and Metabolism Reports

Health care outcomes have been increasingly assessed through health-related quality of life (HRQoL) measures. While the introduction of nitrogen-scavenging medications has improved survival in patients with urea cycle disorders (UCDs), they are often associated with side effects that may affect patient compliance and outcomes.Symptoms commonly associated with nitrogen-scavenging medications were evaluated in 100 adult and pediatric participants using a non-validated UCD-specific questionnaire. Patients or their caregivers responded to a pre-defined list of symptoms known to be associated with the use of these medications. Responses were collected at baseline (while patients were receiving sodium phenylbutyrate [NaPBA]) and during treatment with glycerol phenylbutyrate (GPB).After 3 months of GPB dosing, there were significant reductions in the proportion of patients with treatment-associated symptoms (69% vs. 46%; p < 0.0001), the number of symptoms per patient (2.5 vs. 1.1; p < 0.0001), and frequency of the more commonly reported individual symptoms such as body odor, abdominal pain, nausea, burning sensation in mouth, vomiting, and heartburn (p < 0.05). The reduction in symptoms was observed in both pediatric and adult patients. The presence or absence of symptoms or change in severity did not correlate with plasma ammonia levels or NaPBA dose.The reduction in symptoms following 3 months of open-label GPB dosing was similar in pediatric and adult patients and may be related to chemical structure and intrinsic characteristics of the product rather than its effect on ammonia control.

Psychometric analysis of a Persian version of the European Organization for Research and Treatment of Cancer OG25 Quality of Life Questionnaire in oesophagogastric cancer patients.

Health-related quality of life (HRQL) is a fundamental outcome in oncology patients and quality of life (QOL) assessment requires clinically relevant questionnaires. The purpose of this study was translation and definition of measurement properties and the clinical validity of Quality of Life Questionnaire (QLQ) -OG25 module in Persian patients with oesophagus, oesophagogastric junction (OGJ) or gastric cancers. The translation procedure followed European Organization for Research and Treatment of Cancer (EORTC) guidelines. Both EORTC QLQ-OG25 and a core questionnaire (EORTC QLQ-C30) were administered to patients with oesophagus (150), OG junction (93) and gastric (32) cancer undergoing multi-modal treatments. Convergent and discriminant validity, Cronbach's alpha coefficient and known-groups comparisons were used to examine reliability and validity. In all, 275 patients (mean age 62 years) completed both questionnaires. Compliance rate was high and the questionnaire module was well accepted. We found good reliability for multi-item subscales of QLQ-OG25 (Cronbach's alpha coefficients 0.76-0.89). About 73% had TNM staging and scales distinguished between clinically distinct groups of patients. However, patients in palliative group experienced compromised functional status and worse treatment-associated symptoms than those in the potentially curative group. Test-retest scores were consistent. Multi-trait scaling analysis demonstrated good convergent and discriminant validity. Overall, the Persian version of QLQ-OG25 demonstrated psychometric and clinical validity that supports its application as a supplement to the original tool (EORTC QLQ-C30) when assessing HRQL in patients with upper-gastrointestinal (GI) cancer both in curative and palliative phases.

Comparative impact of treatment on patient reported outcomes (PROs) in patients with glioblastoma (GBM) enrolled in RTOG 0825.

2003 Background: RTOG 0825 tested if adding bevicizumab (BEV) to standard chemoradiation improves survival (OS) or progression free survival (PFS) in newly diagnosed GBM. While OS was equivalent, PFS was longer with Bev (Arm 2) than with placebo (Arm 1). Patients completed quality of life and symptom PROs to evaluate clinical benefit. Methods: The M.D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) and the EORTC core Quality of life Questionnaire and brain tumor module (EORTC QLQ-C30/BN20), were completed by pts at baseline (B) and longitudinally (wk 6, 10, 22, 34, and 46) while on study. The difference between treatment arms were compared from B with evaluation in subsequent weeks in those pts without disease progression; and early change (EC) (baseline to wk 10) between those with and without progression as predictors for OS and PFS. Results: 542pts consented to participate on this trial, and 507 randomized pts participated, with completion of forms by 94% at baseline, 75% at wk 10, 61% at wk 22, and 58% at wk 34. There was a trend for all MDASI-BT symptom groupings to be worse in Arm 2, with significant findings in treatment symptoms at wk 22 and wk 34; both affective and generalized disease symptoms were also significantly worse. For EORTCQLQ30/BN20, differential effects varied at each time point, with no persistent differences. For the MDASI-BT, B neurologic symptom grouping and EC in cognitive symptoms were prognostic for both OS and PFS. For the EORTC QLQ30/BN20, global QOL and motor dysfunction at B as well as EC in communication and leg weakness were prognostic for OS; whereas physical function at B and EC in headaches, seizures, and weak legs were prognostic for PFS. Conclusions: The longitudinal collection of PROs in this phase III trial revealed important treatment-related differences as there was overall more deterioration in symptoms and QOL in Arm 2 as compared to Arm 1, with persistent significant differences in treatment associated symptoms. B and EC tumor associated symptoms on both PRO tools were prognostic for OS and PFS. Longitudinal modeling is ongoing to further assess for differential impact of treatment on symptoms and QOL. Support: U10 CA21661, U10 CA37422 and Genentech, Inc. Clinical trial information: NCT00884741.

Neuropsychiatric Complications of Efavirenz Therapy: Suggestions for a New Research Paradigm

Neuropsychiatric Complications of Efavirenz Therapy: Suggestions for a New Research Paradigm

Improved supportive care in pancreatic carcinoma UICC stages I–IV patients using fermented mistletoe (Viscum album L.) extract

Background The fermented mistletoe extract Iscador ® (ISC) is applied in supportive care of surgically treated pancreatic carcinoma patients to reduce adverse drug reactions (ADR) induced by conventional therapy (ConTh) and to improve quality of life (QoL). Methods In a multicenter comparative non-interventional cohort study, efficacy and safety of ISC given additionally to ConTh (gemcitabine and/or 5-fluorouracil and/or radiotherapy) were investigated and compared to a parallel control group without ISC. Unselected standardized anonymized data from medical records of patients meeting the eligibility criteria were followed-up until last visit or death. As statistical endpoints ADR related to ConTher, disease- and treatment-associated symptoms, duration of hospitalization, and overall survival (OS) were evaluated. All endpoints were adjusted to confounders. Results From 17 centers we could evaluate a total of 396 (201 ISC and 195 control) surgically treated patients. Follow-up was (median) 15.2 vs. 10.1 months, and ISC therapy duration (median) 15.0 months. Significantly fewer ISC (13.7%) than control patients (48.9%) developed ADR by ConTh ( p p p =0.001), with a 42% relative hazard reduction. No severe ISC-related ADRs or tumor enhancement were observed. Conclusion The ISC-treated group showed significantly fewer ConTh-induced ADRs, fewer disease- and therapy-related symptoms, shorter hospitalization, and a longer OS. The ISC-treatment was well tolerated and appears beneficial in supportive care in patients with all stages of pancreatic carcinoma.

Quality of life of patients with gastric cancer in Taiwan: validation and clinical application of the Taiwan Chinese version of the EORTC QLQ‐C30 and EORTC QLQ‐STO22

The relatively high incidence of gastric cancer in Taiwan warranted the need of a disease-specific quality of life (QOL) instrument. We translated the EORTC QLQ-C30 and QLQ-STO22 according to the guidelines from the EORTC. A total of 100 patients were interviewed. Convergent and discriminant validity, Cronbach's alpha coefficient and known-groups comparisons were used to examine the reliability and validity. We found good reliability for multi-item subscales of the QLQ-C30 and QLQ-STO22 (Cronbach's alpha coefficient: 0.70-0.94) except cognitive functioning of the QLQ-C30 and eating restriction of the QLQ-STO22. Patients in the active treatment group experienced compromised functional status and worse treatment-associated symptoms than those in the follow-up group. Similar results were found in comparisons based on Eastern Cooperative Oncology Group (ECOG) Performance Status and dysphagia grades. The study has ascertained the cross-cultural validity, reliability and clinical applicability of the Taiwan Chinese version of the EORTC QLQ-C30 and QLQ-STO22.

N-3 Polyunsaturated fatty acids throughout the cancer trajectory: influence on disease incidence, progression, response to therapy and cancer-associated cachexia

Evidence from epidemiological studies suggests that diets rich in n-3 PUFA may be associated with reduced cancer risk. These observations have formed the rationale for exploring the mechanisms by which n-3 PUFA may be chemoprotective and have resulted in significant advances in our mechanistic understanding of n-3 PUFA action on tumour growth. Various interrelated and integrated mechanisms may be at work by which n-3 PUFA influence cancer at all stages of initiation, promotion, progression, and neoplastic transformation. More recently, experimental studies have reported enhanced tumour cell death with chemotherapy when fish oil is provided while toxic side effects to the host are reduced. Furthermore, cancer-associated wasting has been shown to be attenuated by fish oil supplementation. Clinical evidence suggests that the n-3 PUFA status of newly diagnosed cancer patients and individuals undergoing chemotherapy is low. Therefore, both the disease itself and therapeutic treatments may be contributing factors in the decline of n-3 PUFA status. Dietary supplementation to maintain and replenish n-3 PUFA status at key points in the cancer disease trajectory may provide additional health benefits and an enhanced quality of life. The present review will focus on and critically examine current research efforts related to the putative anti-cancer effects of n-3 PUFA and their suggested ability to palliate cancer-associated and treatment-associated symptoms.