Systemic Therapy Side Effects Research Articles

Abstract CT033: Phase I study of intraventricular infusions of autologous exvivo expanded NK cells in children with recurrent/refractory malignant posterior fossa tumors of the central nervous system

Abstract Scientific background/rationale: The prognosis of recurrent/refractory medulloblastoma (MB), ependymoma (EP) and atypical teratoid/rhabdoid neoplasms (AT/RT), which constitutes the majority of malignant posterior fossa tumors (MPFT) in children, remain dismal with no defined effective therapy. Current treatment strategies have significant toxicities and thus profiling newer trials with clinical efficacy and minimal side-effects are imperative. Advantages of direct infusion of natural killer (NK) cells into the ventricles could enhance therapeutic efficacy by maximally concentrating them in the central nervous system (CNS) near the tumor area, bypassing the blood brain barrier and alleviating toxicity as seen with systemic chemotherapy. We have shown the efficacy of activated and propagated NK cells to lyse and kill the MPFT in vitro and tumor explants in mice models. Also, in a first-time human in vivo pilot study, we demonstrated the feasibility of infusions of biologic agents into the fourth ventricle. Infusing biologic agents through catheters placed in the lateral ventricles are well established in neurooncology. The current ongoing study is the first-in-human, loco-regional infusion of NK cells directly into the brain evaluating safety with intent to avoid the significant side-effects of systemic therapy. This novel trial will hopefully be able to provide therapeutic efficacy and a significant increase in the survival of these children. The current format of this trial incorporates changes including different dose, schedule, routes of intraventricular infusions of NK cells from the previously presented version of the trial, and thus submitted. Correlative studies: Cerebrospinal fluid (CSF) drawn during infusions of NK cells will be evaluated for the immunophenotype, function, persistence of NK cells and influx or presence of any other immune cells and correlating with tumor response. Methods: This trial (NCT02271711-recruiting) will proceed with infusions of NK cells directly into the lateral or fourth ventricles, after placement of a catheter at that location. Recurrent or refractory MB, AT/RT and EP involving the brain and/or spine at original diagnosis or relapse with histological verification will be eligible. Three to six evaluable patients may be entered at a dose level in this study for determination of maximum tolerated dose (MTD). A minimum of nine patients and a maximum of twenty-four patients will be enrolled. After autologous expanded NK cell product have been manufactured as per good manufacturing practice (GMP) guidelines and released, patients will receive three cycles of NK cell infusions over 12 weeks. Each cycle consists of one infusion per week for three weeks followed by a rest week (week 4). Dosing is based on recipient body surface area (BSA), and three dose levels will be evaluated. Currently, the trial is in the second cohort, with no dose limiting toxicity (DLT) noted with the previous dose level. 35% of the minimal accrual has been met. Also as a secondary aim, we will evaluate the antitumor activity of the NK cell infusions within the confines of a phase I study Citation Format: Soumen Khatua, Vidya Gopalakrishnan, Laurence Cooper, Dean Lee, David I. Sandberg, Michael Rytting, Jason J. Johnson, Leena Ketonen, Diane Liu, Judy Moyes, Wafik Zaky. Phase I study of intraventricular infusions of autologous exvivo expanded NK cells in children with recurrent/refractory malignant posterior fossa tumors of the central nervous system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT033. doi:10.1158/1538-7445.AM2017-CT033

Worsening of rest-activity circadian rhythm and quality of life in female breast cancer patients along progression of chemotherapy cycles

ABSTRACTChemotherapy and its associated side effects can induce the disruption of circadian rest-activity rhythm and may have negative consequences on health-related quality of life (HRQoL) of cancer patients. In the current study, repeated-measures cross-sectional design was implemented to determine the status of circadian rest-activity rhythm and to assess the HRQoL of newly diagnosed female breast cancer patients those were planned to receive six cycles of chemotherapy. Rest activity and HRQoL were assessed in twenty-five patients during chemotherapy cycles 1st (C1), 3rd (C3), and 6th (C6) immediately after they reported to the outdoor ward of the Regional Cancer Center, Pt. J.N.M. Medical College, Dr. B.R. Ambedkar Memorial Hospital, Raipur, India. Wrist actigraphs for consecutive spans of 3–4 days were used to record the rest-activity rhythm, and its parameters were computed with the help of Cosinor Rhythmometry. Quality of life (QoL) parameters were assessed using EORTC QLQ-C30 and QLQ-BR23. Results revealed that average scores of all rhythm parameters, such as MESOR, amplitude, acrophase, rhythm quotient, circadian quotient, peak activity, dichotomy index, and autocorrelation coefficient; and all functional scales of QLQ-C30, such as physical, role, emotional, cognitive, and social, and global quality of life statistically significantly decreased with the increasing number of chemotherapy cycles (C1 to C3 and C6). Scores of symptom scales of QLQ-C30, such as fatigue, pain, dyspnoea, insomnia, appetite loss, and diarrhea increased significantly from C1 to C6. Among the QLQ-BR23 scales, scores of sexual functioning, sexual enjoyment, breast symptoms, and arm symptoms significantly decreased, whereas scores of systemic therapy side effects, and upset by hair loss significantly increased across the chemotherapy cycles. We conclude that rest-activity rhythm disrupted and HRQoL of breast cancer patients worsened along the increasing number of chemotherapy cycles. We suggest that along with the treatment protocol, level of disruption of these parameters should be assessed and managed with the proper interventions that prominently include timing of the chemotherapy administration. The latter is pivotal for maintenance of these parameters, which are likely to enhance the physiological ability of patients for better treatment responses and may improve the overall QoL and survival of the patients.

Structural distress screening and supportive care for patients with lung cancer on systemic therapy: A randomised controlled trial

IntroductionGaining regular insight into the nature and severity of distress by a psychosocial nurse coupled with referral to psychosocial and/or paramedical healthcare provider(s) is an experimental supportive care approach. We sought to examine the effects of this approach on quality of life (QoL), patient's mood and satisfaction, end-of-life care and survival in patients with lung cancer. MethodsPatients with newly diagnosed or recurrent lung cancer starting systemic therapy were randomly assigned to receive usual care or the experimental approach. Patients were followed up at 1, 7, 13 and 25 weeks after randomisation with the EORTC-QLQ-C30, the European Quality of Life-5D, the Hospital Anxiety and Depression Scale and the Patient Satisfaction Questionnaire-III. Primary outcome was the mean change in the EORTC-QLQ-C30 global QoL-score between 1 and 25 weeks. ResultsA total of 223 patients were randomised of whom 111 (50%) completed all four assessments (44% in the usual care group versus 55% in the experimental group). No significant difference was found in the mean change global QoL-score (−2.4, 95% CI: 12.1–7.2; P = 0.61), nor in the other patient-reported outcomes. Fewer patients in the experimental group received chemotherapy shortly before the end-of-life, and median survival was comparable (10.3 versus 10.1 months, P = 0.62). Of the 112 dropouts, 33 died and 79 discontinued participation for other reasons. ConclusionsThis supportive care approach neither improved QoL nor other patient-reported outcomes in patients with lung cancer. However, it reduced the use of chemotherapy shortly before the end of life. Possibly, (late) side effects of systemic therapy may have obscured effects of our intervention on QoL. Clinical trial registrationNTR3540.

Relationship between anxiety disorders and domains of health related quality of life among Nigerians with breast cancer

PurposeHealth Related Quality of life (HRQoL) is increasingly recognised as an important indicator of outcome and well-being in oncology care. We set out in this study to evaluate whether significant association exists between anxiety disorders (ADs) and HRQoL in breast cancer, such that any intervention addressing ADs would potentially improve HRQoL. MethodsA cross sectional evaluation of 200 attendees of an oncology clinic was done using designed questionnaire to gather socio-demographic and clinical data. Subsequently, the Schedule for clinical Assessment in Neuropsychiatry was used to ascertain ADs and the European Organization for Research and Treatment of Cancer QOL Questionnaire (THE EORTC QLQ-C30) Version 3 with its breast specific supplement (QLQ-BR-23) was used to profile HRQoL in participants. ResultsThe mean age of participants was 49.6(±11.2) years, and 54% of participants had stage III and IV breast cancer. Findings on EORTC QLQ-C30 following univariate analyses showed association between ADs and poorer mean scores on global health status, functional domains including physical, emotional, social, and cognitive functions (p < 0.05). On the symptom scale, those with ADs had higher symptom load including fatigue, pain, insomnia, appetite loss, diarrhoea and financial difficulties (p < 0.05). Similarly, the QLQ-BR-23 showed correlation between ADs and poorer mean scores on breast cancer specific issues like body image, future perspectives, sexual functioning, sexual enjoyment, systemic therapy side-effects, upset by hair loss and breast symptoms (p < 0.05). Findings after controlling for age, treatment, cancer duration, recurrence and stage showed the same pattern of relationship between ADs and HRQoL; however, the global health status, cognition, sexual functioning, and higher symptom load with respect to appetite loss and financial difficulties were not independently related with ADs. ConclusionsScaling up of oncological services, supportive care and targeted psychosocial interventions are indicated for optimal outcome of breast cancer. Longitudinal research with focus on the complex relationship between HRQoL and ADs along with their modifiable determinants across the trajectories of breast cancer is warranted.

Good practice guideline: Promoting Early Identification of Systemic Anti-Cancer Therapies Side Effects: – Two Approaches.

This guidance has been produced by the National Chemotherapy Board in response to concerns that patients often delay reporting serious Systemic Anti-Cancer Therapy (SACT) side effects to dedicated help lines. Two complementary approaches to improve side effect reporting are suggested: •Empowerment focuses on equipping patients to take responsibility for identifying and reporting important side effects and may be mediated via technology. •Proactive monitoring includes clinician interventions (e.g. telephone support or home visits).

Open access follow-up care for early breast cancer: a randomised controlled quality of life analysis.

This study evaluated the acceptability of a supportive model of follow‐up. One hundred and twelve women recovering from breast cancer were randomised to receive standard breast clinic aftercare (Control n = 56) or on demand by open access aftercare by breast care nurses (Intervention n = 56). Participants attended a support‐based psycho‐educational programme delivered in four half‐day group sessions. Three quality of life questionnaires (EORTC QLQ‐C30, QLQ‐BR23, HADS) were administered at baseline and 6‐monthly intervals for 2 years. Multilevel linear regression modelling methods were used for evaluation. Age was found to be a statistically significant predictor of quality of life in several sub‐scales. Increasing age was negatively associated with sexual functioning, systematic therapy side effects and physical functioning, and positively associated with future perspective. Aftercare assignment was not found to be a statistically significant predictor. Women treated for early breast cancer were not disadvantaged by allocation to the open access supportive care model in terms of quality of life experienced. The model for follow‐up was demonstrated to be a feasible alternative to routinised hospital‐based follow‐up and adds to the evidence for stratified follow‐up for low‐risk cancer patients, incorporating self‐management education. Stratified follow‐up pathways are viewed as a preferable approach.

Short term quality of life with epirubicin-fluorouracil-cyclophosphamid (FEC) and sequential epirubicin/cyclophosphamid-docetaxel (EC-DOC) chemotherapy in patients with primary breast cancer – Results from the prospective multi-center randomized ADEBAR trial

BackgroundThe recommendation for adjuvant dose-dense chemotherapy in high risk primary breast cancer is heterogeneous among guidelines. Understanding the impact on QoL is thereby a crucial factor, especially if the benefit is potentially low. This study aims to assess QoL as a secondary outcome in the prospective randomized multi-center ADEBAR trial. MethodsQoL was assessed at baseline (t1), before cycle 4 FEC and cycle 5 EC-DOC (t2), 4 weeks after chemotherapy (t3) and 6 weeks after radiation (t4) using the European Organization for Research and Treatment for Cancer (EORTC) Quality of Life Core Questionnaire (QLQ-C30) and the Breast Cancer-Specific Module (QLQ-BR23). Results1306 patients were enrolled into the ADEBAR trial. 675 were assigned to the FEC and 688 to the EC-DOC arm. After the beginning of treatment, global QoL dropped in both arm by 3–4 points. In the EC-DOC arm, QoL dropped further at t3 by 7 points and stayed stable in the FEC arm. 6 weeks after radiation, QoL exceeded baseline in both arms by 6–8 points. The differences between treatment arms were strongest at t3 (53.0 vs. 49.5) but did not reach clinical relevance at any point in time. Physical functioning, nausea and vomiting, fatigue and systemic therapy side effects followed with some minor exceptions similar patterns but showed higher amplitudes. ConclusionIn conclusion, we could not detect a clinically relevant difference between the two treatment arms in global QoL, although the results consistently show that patients on EC-DOC report worse scores during the treatment.

The Reduction in Upper Extremity Volume and Improved Quality of Life in Women With Post-Mastectomy Lymphedema by Complex Decongestive Therapy

Background: Breast cancer is one of the most common malignancies all over the world. The rate of survival of the patients with cancer has increased due to developing diverse treatment methods, as a result of which the treatment-related side effects have become the focus of attention more than before. Lymphedema related to breast cancer is one of the frequent side effects which has significantly affected the patient’s quality of life. Objectives: The purpose of this research was to assess the effect of complete or complex decongestive therapy on breast cancer-related lymphedema and the patients’ quality of life. Patients and Methods: The present study was conducted from January 2013 to January 2014 and comprised 119 patients with breast cancer, related lymphedema, who had undergone complete or complex decongestive therapy (CDT). The patients’ volume and grade of lymphedema were measured and determined before and after treatment, using the direct volumeter device to measure the lymphedema volume. To determine the quality of life, the European organization for research and treatment of cancer quality of life questionnaire (EQRTC BR-23) was completed before and after the treatment. Result: The volume of lymphedema was significantly reduced after CDT (P < 0.001). The scores of quality of life were significantly increased regarding body image (BI) (P < 0.001), future prospective (FP) (P = 0.008), sexual functioning (SF) (P = 0.006), systemic therapy side effect (STSE) (P = 0.008) and arm symptoms (AS) (P < 0.001) which was clear indication of improved quality of life. Conclusions: It is concluded that not only CDT causes reduction in lymph edema volume but also it improves the life quality of patients with breast cancer-related lymphedema

Abstract P1-12-03: Short term quality of life with epirubicin-fluorouracil-cyclophosphamid (FEC) and sequential epirubicin/cyclophosphamid-docetaxel (EC-DOC) chemotherapy in patients with primary breast cancer – Results from the prospective multi-center randomized Adebar trial

Abstract Background: The grade of recommendation for adjuvant dose-dense chemotherapy in patients with high risk primary breast cancer is heterogeneous among international guidelines. Understanding the impact on quality of life (QOL) by adjuvant dose dense chemotherapy in comparison to standard adjuvant chemotherapy is thereby a crucial factor, especially if the benefit is potentially low. This study aims to assess the impact on QOL by adjuvant dose dense chemotherapy in the prospective randomized multi-center ADEBAR trial. Methods: QOL was assessed at baseline (t1), before cycle 4 FEC (Epirubicin 60mg/m2 i.v. d 1 + 8, 5-Fluoruracil 500mg/m2 i.v. d 1 + 8, Cyclophosphamide 75mg/m2 p.o. d 1–14, q4w x 6) and cycle 5 EC-DOC (Epirubicin 90mg/m2 plus Cyclophosphamide 600mg/m2 q3w x 4, sequentially followed by Docetaxel 100mg/m2 q3w x 4) (t2), 4 weeks after chemotherapy (t3), 6 weeks after radiation (t4) and 1 year after baseline (t5) using the European Organization for Research and Treatment for Cancer (EORTC) Quality of Life Core Questionnaire (QLQ-C30) and the Breast Cancer-Specific Module (QLQ-BR23). A multivariate mixed model was fitted to test for differences between the two treatment arms. Primary endpoint was global QOL, secondary endpoints physical functioning, nausea&amp;vomiting, fatigue and systemic therapy side effects. A minimum clinically meaningful difference was considered to be 10 points. Results: 1306 patients were recruited between 3/2002 and 5/2005 675 were assigned to the FEC and 688 to the EC-DOC arm. Compliance to QOL assessment was 74% at baseline and 58% four weeks after therapy, but dropped to 11% after one year follow up. After the beginning of treatment global QOL dropped in both arm by 3 to 4 points. In the EC-DOC arm QOL dropped further at t3 by 7 points and stayed stable in the FEC arm. 6 weeks after radiation QOL exceeded baseline in both arms by 6 to 8 points. The differences between treatment arms were strongest at t3 (54.1 vs. 49.7) but did not reach clinical relevance at any point in time. Physical functioning, nausea vomiting, fatigue and systemic therapy side effects followed with some minor exceptions similar patterns, but showed higher amplitudes. Conclusion: In conclusion we could not detect a statistically significant difference between the two treatment arms in QOL parameters, indicating that dose dense adjuvant chemotherapy did not impact QOL at a clinically relevant level compared to standard adjuvant chemotherapy. Citation Format: Schwentner L, Harbeck N, Singer S, Eichler M, Rack B, Forstbauer H, Wischnik A, Scholz C, Fink V, Huober J, Friedl T, Weissenbacher T, Härtl K, Kiechle M, Janni W. Short term quality of life with epirubicin-fluorouracil-cyclophosphamid (FEC) and sequential epirubicin/cyclophosphamid-docetaxel (EC-DOC) chemotherapy in patients with primary breast cancer – Results from the prospective multi-center randomized Adebar trial. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-12-03.

Abstract P1-10-31: Impact of increased physical activities after diagnosis on fatigue and overall pain during cancer treatment: A prospective cohort study

Abstract Background Existing evidence strongly suggests that exercise is not only safe but also feasible during cancer treatment. Physical activity is recommended for improving multiple post-treatment adverse effects on bone health, muscle strength, and other quality-of-life measures. Yet, limited evidence exists regarding effect of increased physical activity after diagnosis on symptoms management of breast cancer patients. Methods A total of 422 patients were recruited from July 2010 to July 2011 at two cancer hospitals in Seoul, Korea. Physical activity in sports (PAS) was assessed using Minnesota Leisure Time Physical Activity Questionnaire before and 2 weeks, 3-, 6-, 12-, 24- and 36-months after diagnosis. Physical symptoms including fatigue, pain, arm symptom, and insomnia were measured using EORTC-C30 and BR23. Growth mixture models were used to identify trajectory classes of physical activity patterns. Multivariate analysis was used to find impact of PAS on symptom management using SAS. Results Three distinct PAS groups were identified according to 3-year change patterns: moderate to moderate (MM): 40.8%, none to moderate (NM): 31.1% and moderate to high (MH): 28.1%. The LM and MH group increased PAS from diagnosis but it began to decrease from 1 year after diagnosis. Compared to the MM, the NM and MH reported significantly lower level of fatigue (MM:40.7, NM:32.2, MH:33.7), pain(MM:28.0, NM:25.6, MH:20.6), systemic therapy side effects (MM:26.9, NM:22.6, MH:21.8), and breast symptoms (MM:25.4, NM:21.7, MH:20.2) during active treatment (6 months after diagnosis). Change patterns of quality of life according to trajectory groups At diagnosis2 weeks3 months6 months12 months24 months36 monthsFatigueMM31.3±1.930.2±1.935.3±2.0140.7±2.1137.8±2.1138.5±2.1141.0±2.21NM30.2±1.928.2±1.931.9±2.132.2±2.2233.6±2.135.6±2.2137.8±2.31MH28.8±2.327.4±2.233.0±2.433.7±2.51233.9±2.4136.2±2.5137.1±2.51PainMM15.1±1.531.3±1.9123.2±2.0128.0±2.0123.5±2.0122.0±2.0121.2±1.91NM15.4±1.532.4±2.023.3±2.0125.6±2.122.7±2.021.1±2.123.8±2.01MH17.2±1.828.4±2.3121.2±2.320.6±2.4219.7±2.321.1±2.318.6±2.2Systemic therapy side effectsMM16.8±1.114.3±1.2133.2±1.7126.9±1.5125.4±1.5126.2±1.6128.6±1.71NM15.0±1.114.5±1.235.2±1.7122.6±1.61222.0±1.6124.5±1.7127.7±1.81MH15.6±1.412.9±1.4134.4±2.0121.8±1.81221.8±1.7122.1±1.9124.7±2.01Breast symptomsMM13.8±1.226.4±1.6120.8±1.5125.4±1.6123.6±1.6119.2±1.7119.6±1.71NM13.0±1.224.7±1.6119.6±1.5121.7±1.61222.3±1.7119.9±1.8119.1±1.81MH16.0±1.424.1±1.8119.4±1.820.2±1.81217.8±1.8217.4±2.014.0±1.92*adjusted with age, stage, and radiotherapy 1 p&amp;lt;0.05 (differences from baseline within group), 2 p&amp;lt;0.05 (differences from MM group within time) Conclusion The results of the study confirmed that increased physical activity after diagnosis, even with patients who did not exercise at all before diagnosis, helps to control fatigue, pain, systemic side effects, and breast symptoms during treatment. It is necessary to find ways to promote physical activity after diagnosis and help patients to stay active during treatment. Citation Format: Lee JK, Kang D, Choi E-K, Kong S, Lee S-K, Lee JE, Han W, Park YH, Ahn JS, Im YH, Noh D-Y, Nam S-J, Cho J. Impact of increased physical activities after diagnosis on fatigue and overall pain during cancer treatment: A prospective cohort study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-10-31.

Safety and Efficacy of Intravitreal Ganciclovir Injections More than 10 Times for Cytomegalovirus Retinitis

Purpose: To study the treatment outcomes in patients who were administered multiple intravitreal ganciclovir injections more than 10 times alone without systemic anti-cytomegalovirus therapy for cytomegalovirus retinitis. Case summary: A 64-year-old man who underwent immunosuppressive therapy after thymectomy due to an invasive thymoma and pure red-cell aplasia, a 60-year-old woman who underwent chemotherapy after diagnosis of diffuse large B-cell lymphoma, a 49-year-old man with a history of bone marrow transplantation due to acute myeloid leukemia, a 29-year-old woman with dermatomyositis treated with oral steroids and cyclosporine, and a 47-year-old woman who received intravitreal dexamethasone implant injections, intravitreal and subtenon steroid injections due to Behcet's disease were diagnosed with cytomegalovirus retinitis. All patients showed systemic complications such as pancytopenia after systemic anti-cytomegalovirus therapy, and therefore, they were administered multiple intravitreal ganciclovir injections alone. Best-corrected visual acuities improved in all patients, except in one case, where viral lesions were observed in the fovea. Retinal hemorrhaging and infiltrative lesions decreased in all patients. No severe complication was observed during the injection and in the follow-up period. Conclusions: Multiple intravitreal ganciclovir injections alone can be used as a treatment modality for cytomegalovirus retinitis to avoid the systemic side effects of systemic anti-cytomegalovirus therapy. J Korean Ophthalmol Soc 2016;57(2):316-323

Quality of Life in CAM and Non-CAM Users among Breast Cancer Patients during Chemotherapy in Malaysia.

BackgroundComplementary and alternative medicine (CAM) use has become increasingly popular among patients with cancer. The purposes of this study were to compare the QOL in CAM users and non-CAM users and to determine whether CAM use influences QOL among breast cancer patients during chemotherapy.MethodologyA cross-sectional survey was conducted at two outpatient chemotherapy centers. A total of 546 patients completed the questionnaires on CAM use. QOL was evaluated based on the European Organization for Research and Treatment of Cancer (EORTC) core quality of life (QLQ-C30) and breast cancer-specific quality of life (QLQ-BR23) questionnaires.ResultsA total of 70.7% of patients were identified as CAM users. There was no significant difference in global health status scores and in all five subscales of the QLQ C30 functional scales between CAM users and non-CAM users. On the QLQ-C30 symptom scales, CAM users (44.96±3.89) had significantly (p = 0.01) higher mean scores for financial difficulties than non-CAM users (36.29±4.81). On the QLQ-BR23 functional scales, CAM users reported significantly higher mean scores for sexual enjoyment (6.01±12.84 vs. 4.64±12.76, p = 0.04) than non-CAM users. On the QLQ-BR23 symptom scales, CAM users reported higher systemic therapy side effects (41.34±2.01 vs. 37.22±2.48, p = 0.04) and breast symptoms (15.76±2.13 vs. 11.08±2.62, p = 0.02) than non-CAM users. Multivariate logistic regression analysis indicated that the use of CAM modality was not significantly associated with higher global health status scores (p = 0.71).ConclusionWhile the findings indicated that there was no significant difference between users and non-users of CAM in terms of QOL, CAM may be used by health professionals as a surrogate to monitor patients with higher systemic therapy side effects and breast symptoms. Furthermore, given that CAM users reported higher financial burdens (which may have contributed to increased distress), patients should be encouraged to discuss the potential benefits and/or disadvantages of using CAM with their healthcare providers.

Exploiting a new glycerol-based copolymer as a route to wound healing: Synthesis, characterization and biocompatibility assessment

The use of biocompatible materials based on naturally derived monomers plays a key role in pharmaceutical and cosmetic industries. In this paper we describe the synthesis of a new low molecular weight copolymer, based on glycerol and l-tartaric acid, useful to develop biocompatible dermal patches with drug delivery properties. The copolymer's chemical composition was assessed by FT-IR (Fourier transform infrared spectroscopy), 1H NMR (1H Nuclear Magnetic Resonance) and XPS (X-ray photoelectron spectroscopy), while its molecular weight distribution was estimated by SEC (size exclusion chromatography). Copolymer thermal properties were studied by TGA (thermogravimetric analysis). Biological evaluations by MTT assay and SEM (scanning electron microscopy) observations performed with murine fibroblasts and human keratinocytes (HaCaT) revealed a good compatibility of the proposed copolymer. Ciprofloxacin was selected as model drug and its release was evaluated by HPLC (high performance liquid chromatography), showing that the new copolymer supplied promising results as drug delivery system for wound healing applications. Furthermore, investigations on Skin-Mesenchymal stem cells (S-MSCs) behaviour and gene expression showed that the copolymer and its combination with ciprofloxacin did not affect their stemness. In this regard, the fabrication of dermal patches with new, low cost materials for local treatment of skin infections represents an attractive strategy in order to bypass the worrying side effects of systemic antibiotic therapy. Overall, the performed physico-chemical characterization, drug release test and biological evaluations showed that this new copolymer could be a promising tool for the in situ delivery of bioactive molecules during skin lesions treatment.

Abstract P5-17-03: Quality of life results from a phase 2, multicenter, single-arm study of eribulin mesylate plus trastuzumab as first-line therapy for locally recurrent or metastatic HER2+ breast cancer

Abstract Introduction: Eribulin mesylate is a nontaxane microtubule dynamics inhibitor that has showed an overall survival benefit relative to other commonly used agents in patients with ≥2 prior MBC therapies. Primary data from a phase 2 trial for first-line eribulin + trastuzumab [TRAS] in HER2+ patients with MBC showed an objective response rate of 71%, clinical benefit rate of 84.6%, disease control rate of 96.2%, PFS of 11.6 months, and tolerability similar to known profiles for these agents. Here, we present prespecified QoL, efficacy, and safety/tolerability results. Methods: Patients received eribulin mesylate 1.4 mg/m2 IV on days 1 and 8 of each 21-day cycle and initial TRAS (8 mg/kg IV/day 1), followed by 6 mg/kg on day 1 of each subsequent cycle. Response, PFS, QoL as measured by EORTC QoL assessment tool (QLQ-C30) and QLQ-BR23, and tolerability were assessed. Percentage of patients with at least ±10-point change from baseline was calculated at each visit. Time to deterioration was defined as time from first dose to worsening in QoL score that reached minimally clinically important difference (MID) (ie, 10 points in global health status [GHS] in QLQ-C30) without further improvement of at least MID; this was estimated overall and by response status. Results: At cycle 6 (n=44; completion rate=84.6% of 52 patients enrolled), more patients fell in the stable category (within +/-10 points change from baseline), except for pain (47.7% with improvement), cognitive functioning (45.5% worsening), fatigue and systemic therapy side effects (50% worsening for each), and arm symptoms (47.7% improvement) (Table). Median times to deterioration for GHS/QoL were 7.6 months overall (n=51), and 7.6 and 7.0 months for responders (n=36) and nonresponders (n=15), respectively (HR 0.73; 95% CI 0.32, 1.68; P=0.446). Mean symptom scores in EORTC QLQ-C30 were significantly correlated with corresponding AE rates for fatigue (r=0.31), nausea/vomiting (r=0.50), pain (r=0.41), dyspnea (r=0.49), insomnia (r=0.35), constipation (r=0.30), and diarrhea (0.40; P≤0.03 for all comparisons). The most common treatment-related AEs (all grade incidence ≥25%) were alopecia (88.5%), fatigue (69.2%), peripheral neuropathy (69.2%), neutropenia (59.6%), nausea (46.2%), diarrhea (32.7%), anemia (25%), constipation (25%), and decreased appetite (25%). Table. Qol EORTC QLQ-C30 Scores: Change from Baseline to Cycle 6 (n=44)Functional orCategory, n (%)Symptom ScaleImprovedStableWorsenedGHS/Qol13 (29.5)23 (52.3)8 (18.2)Physical10 (22.7)26 (59.1)8 (18.2)Role13 (29.5)20 (45.5)11 (25.0)Emotional17 (38.6)18 (40.9)9 (20.5)Cognitive6 (13.6)18 (40.9020 (45.5)Social12 (27.3)18 (40.9)14 (31.8)Fatigue14 (31.8)8 (18.2)22 (50.0)Nausea/vomiting9 (20.5)24 (54.5)11 (25.0)Pain21 (47.7)14 (31.8)9 (20.5)Dyspnea12 (27.3)19 (43.2)13 (29.5) Conclusions: Given the improvements in pain and in arm and breast symptoms, long median time to deterioration in functioning/symptom scales in this analysis, and the tumor response rates and safety profile in the primary analysis, combination eribulin/TRAS may be an acceptable treatment option for locally recurrent or HER2+ MBC and merits further study in larger clinical trials. Citation Format: Lee Schwartzberg, Sharon Wilks, Shannon Puhalla, Joyce O'Shaughnessy, Erhan Berrak, James Song, David Cox, Linda Vahdat. Quality of life results from a phase 2, multicenter, single-arm study of eribulin mesylate plus trastuzumab as first-line therapy for locally recurrent or metastatic HER2+ breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-17-03.

Abstract P5-17-02: Quality of life in patients receiving first-line eribulin mesylate for HER2- locally recurrent or MBC

Abstract Introduction: Eribulin mesylate is a nontaxane microtubule inhibitor approved to treat MBC in patients (pts) who previously received ≥2 chemotherapeutic regimens for MBC. A phase 2 study of first-line eribulin for HER2-negative (HER2-) MBC showed an overall response rate of 29%, median 6.8 m progression-free survival, and tolerability consistent with earlier studies. We present prespecified quality of life (QoL) results for this trial. Methods: Pts (N=56) received eribulin mesylate 1.4 mg/m2 IV on days 1 and 8 of each 3-wk cycle (median: 7 cycles). QoL was assessed using the EORTC QoL assessment (QLQ-C30) and a breast-cancer specific questionnaire (QLQ-BR23) pretreatment (baseline) and on day 1 of every other cycle during treatment. Percentage of pts with at least ±10-point change from baseline was summarized descriptively. Linear mixed-effects models were used to evaluate changes over time and compare responders vs nonresponders controlling for baseline score and time effect. Time-to-event analysis was performed on time to deterioration, defined as time from 1st dose to 1st occurrence of worsening in QoL score that reached minimally clinically important difference (MID; eg, 10 points in global health status in QLQ-C30) from baseline without further improvement of at least MID. Results: For QLQ-C30 at cycle 6 (n=29), more pts had at least a 10-point improvement from baseline in role, emotional, and social functioning; fatigue, nausea/vomiting, pain, dyspnea, and insomnia item scores, than had worsening. More pts had worsening in global health status/QoL, cognitive functioning, and diarrhea (Table). Category, n (%) ImprovedStableWorsenedGlobal health status/QoL2 (7)16 (55)11 (38)Physical functioning9 (31)13 (45)7 (24)Role functioning14 (48)10 (35)5 (17)Emotional functioning9 (31)14 (48)6 (21)Cognitive functioning2 (7)13 (45)14 (48)Social functioning10 (35)13 (45)6 (21)Fatigue16 (55)5 (17)8 (28)Nausea and vomiting8 (28)16 (55)5 (17)Pain15 (52)8 (28)6 (21)Dyspnea9 (31)18 (62)2 (7)Insomnia12 (41)15 (52)2 (7)Appetite loss7 (24)16 (55)6 (21)Constipation5 (17)18 (62)6 (21)Diarrhea2 (7)21 (72)6 (21) Median time to deterioration in global health status/QoL was 5.06 m (responders, 8.54 m; nonresponders, 3.71 m; hazard ratio=0.60, P=0.22). In linear mixed models, responders (n=16) performed better than nonresponders (n=40) in role functioning (P=0.011), emotional functioning (P=0.031), fatigue (P=0.007), pain (P=0.047), insomnia (P=0.018), and appetite loss (P=0.032). Mean symptom scores were significantly correlated with corresponding adverse event rates for nausea and vomiting, dyspnea, appetite loss, constipation, and diarrhea; Spearman rank correlation coefficients ranged from 0.31 to 0.54. For QLQ-BR23 at cycle 6, symptom scores were mostly stable; more pts had worsening in body image and systemic therapy side effects than had improvement and more pts had improvement in breast and arm symptoms than had worsening. Responders also had longer time to symptom deterioration. Conclusions: In this study of first-line eribulin treatment for HER2- MBC, a majority of pts had stable or improvement in QoL scales. Responders to eribulin were more likely than nonresponders to have stable or improved QoL. Citation Format: Lee Schwartzberg, Kristi McIntyre, Joyce O'Shaughnessy, Stefan Glück, Erhan Berrak, James Song, David Cox, Linda Vahdat. Quality of life in patients receiving first-line eribulin mesylate for HER2- locally recurrent or MBC [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-17-02.

Determinants of quality of life in patients with breast cancer undergoing external beam radiotherapy.

Quality of life (QoL) of patients with breast cancer is not dependent only on the presence of the disease, as there is such a multitude of social and clinical factors [1, 2]. However, data on the determinants of QoL in Polish breast cancer patients during the course of radiotherapy are scarce and based on custom-made questionnaires [3], rather than the EORTC QLQ-C30 or QLQ-BR23, which are the tools of choice for such patients [4, 5]. We evaluated breast cancer patients undergoing radiotherapy for treatment-related determinants of QoL and compared them with the intensity of depressive symptoms. A total of 98 women with breast cancer during the standard course of external beam radiotherapy agreed to complete the validated Polish versions 3.0 of EORTC QLQ-C30, QLQ-BR23 (all global, functional and symptom scales) and – at the same time point – the Beck Depression Inventory (BDI) to evaluate the intensity of depressive symptoms. A control group of 127 healthy women referred to the mammography department for screening purposes was evaluated using the BDI. Median age of the study group was 54 (25–75%: 46.7–60.5) years. Breast conserving therapy (BCT) had been performed in 50% of patients. In the breast cancer group, 65% of subjects had undergone some form of chemotherapy and 51% were undergoing hormone therapy. Cronbach's α values for QLQ-C30, QLQ-BR23 and BDI were 0.91, 0.81 and 0.83 respectively, confirming adequate test performance. Median total radiation dose given to the patients was 34 Gy (25–75%: 18–42 Gy), and only affected intensity of nausea/vomiting and constipation subscales (R = 0.25, p = 0.04; R = 0.27, p = 0.03 respectively) of the QLQ-C30 functional scales. No statistically significant correlations were found between the total dose and QLQ-BR23 scales, but the early reactions (RTOG staged ≥ 2 [6]) significantly worsened arm symptom subscale score assessment in QLQ-BR23. Hormonal therapy was not significantly correlated with any of those three questionnaires’ subscores. Previously received chemotherapy impacted neither QLQ-C30 nor BDI results, but it was associated with body image (BRBI) and systemic therapy side effect scores (BRST) (p = 0.02 and p = 0.005). Type of surgical intervention before radiotherapy impacted the field of global health status, resulting in better overall QoL in patients who had undergone BCT (58% (25–75%: 50–67) vs. 50% (25–75%: 42–58); p = 0.0405). BCT was also associated with lower reported intensity of breast symptoms (p = 0.0338) and better perception of future perspectives (BRFU; p = 0.0328). The level of depressive symptoms measured in controls was significantly lower than in cancer patients (median 5 (25–75%: 1–10) vs. 12 (25–75%: 6–17) points; p < 0.0001). BDI scores were correlated negatively and significantly with all functional scales of QLQ-C30 (Spearman's correlation coefficients ranging from –0.36 to –0.46, all p < 0.05) and QLQ-BR23 subscales: BRBI and BRFU (R = –0.47 and –0.51; p < 0.05). In conclusion, radiotherapy itself has a minor influence on QoL of breast cancer patients, although organ-specific complications may significantly impair physical functioning. Other forms of oncological treatment, such as the type of surgical procedure performed, have a much more profound impact on all fields of QoL. Intensity of depressive symptoms is an important determinant of QoL in cancer patients which mandates routine psychological evaluation.

Associations of Quality of Life, Physical Activity and Mood States in Women with Breast Cancer Treated with Curative Intent

This study aims to investigate the associations between quality of life, physical activity and mood states in women with breast cancer. A total of 354 women (mean age, 51.74 ± 8.63 years; body mass index (BMI), 28 ± 5.67 kg/m2) completed the Baecke Physical Activity Questionnaire, Profile of Mood States (POMS), European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) and European Organisation for Research and Treatment of Cancer Breast Cancer-Specific Quality of Life Questionnaire (EORTC QLQ-BR23). Pearson’s correlation and multiple linear regressions were used to verify the relations between outcomes and independent variables. Correlations between scores on POMS, Baecke Physical Activity Questionnaire and global health status/quality of life subscale of EORTC QLQ-C30 found associations (p < 0.01) between physical activity (r = 0.191), vigour (r = 0.333) and fatigue (r = −0.433). Multiple linear regression analysis of the global health status/quality of life subscale of the EORTC QLQ-C30 showed significant differences for vigour (p < 0.001), social function (p = 0.003), side effects of systemic therapy (p = 0.019), arm and breast symptoms (p < 0.001) and Baecke physical activity score (p = 0.006). Physical activity is an independent factor related to the quality of life in women with breast cancer. Understanding these variables may influence clinical decisions during treatment and allow positive interventions regarding symptoms, functions and lifestyle.

Beneficial Effects of Pranic Meditation on the Mental Health and Quality of Life of Breast Cancer Survivors.

Breast cancer survivors frequently present long-lasting impairments, caused either by the disease or its treatment, capable of compromising their emotional health and quality of life. Meditation appears to be a valuable complementary measure for overcoming some of these impairments. The purpose of the present investigation was to assess the effect of pranic meditation on the quality of life and mental health of breast cancer survivors. This study was a prospective single-arm observational study using before and after measurements. The subjects were 75 women submitted either to breast cancer therapy or to posttherapy control who agreed to practice pranic meditation for 20 minutes, twice a day, during 8 weeks, after receiving a formal training. The quality of life of the practitioners was assessed by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and EORTC BR-023 questionnaires, and the mental health status by the Goldberg's General Health Questionnaire. After 8 weeks of pranic meditation practice, the subjects showed a significant improvement of their quality of life scores that included physical (P = .0007), role (P = .01), emotional (P = .002), and social functioning (P = .004), as well as global health status (P = .005), fatigue (P < .0001), pain (P = .007), sleep disturbances (P = .01), body image (P = .001), arm symptoms (P = .007), and breast symptoms (P = .002). They also showed a reduction of the side effects of systemic therapy (P = .02) and being upset by hair loss (P = .02). Moreover, meditation was associated with improvement of the mental health parameters of the practitioners that included psychic stress (P = .001), death ideation (P = .02), performance diffidence (P = .001), psychosomatic disorders (P = .02), and severity of mental disorders (P = .0003). The extension of the meditation period from 8 to 15 weeks caused no substantial extra benefits in practitioners. The results of this pilot study showed that breast cancer survivors presented significant benefits related to their mental health and quality of life scores after a short period of practice of pranic meditation, consisting of simple and easy-to-learn exercises. However, because of the limitations of the study, further research is required using a more rigorous experimental design to ascertain whether pranic meditation may be an acceptable adjunct therapy for cancer patients.

Impact of response shift on time to deterioration in quality of life scores in breast cancer patients.

BackgroundThis prospective multicenter study aimed to study the impact of the recalibration component of response-shift (RS) on time to deterioration (TTD) in health related quality of life (QoL) scores in breast cancer (BC) patients and the influence of baseline QoL expectations on TTD.MethodsThe EORTC-QLQ-C30 and BR-23 questionnaires were used to assess the QoL in a prospective multicenter study at inclusion (T0), at the end of the first hospitalization (T1) and, three (T2) and 6 months after the first hospitalization (T3). Recalibration was investigated by the then-test method. QoL expectancy was assessed at diagnosis. Deterioration was defined as a 5-point decrease in QoL scores, considered a minimal clinically important difference (MCID). TTD was estimated using the Kaplan-Meier method. Cox regression analyses were used to identify factors influencing TTD.ResultsFrom February 2006 to February 2008, 381 women were included. Recalibration of breast cancer patients' internal standards in the assessment of their QoL had an impact on TTD. Median TTD were significantly shorter when recalibration was not taken into account than when recalibration was taken into account for global health, role-functioning, social-functioning, body-image and side effects of systemic therapy. Cox multivariate analyses showed that for body image, when recalibration was taken into account, radiotherapy was associated with a shorter TTD (HR: 0.60[0.38–0.94], whereas, no significant impact of surgery type on TTD was observed. For global health, cognitive and social functioning dimensions, patients expecting a deterioration in their QoL at baseline had a significantly shorter TTD.ConclusionsOur results showed that RS and baseline QoL expectations were associated with time to deterioration in breast cancer patients.

Side-effects of systemic therapy for the management of breast cancer.

Systemic treatment for breast cancer is given as neoadjuvent therapy to reduce tumour bulk before surgery, and as adjuvant therapy after surgery to control micrometastatic disease, reduce tumour bulk and improve quality of life in metastatic disease. Systemic therapy is divided into endocrine therapy, chemotherapy and biological response modifier therapy. All therapies will cause a higher rate of anxiety and depression, and loss of libido, which for many is a major problem. In pre-menopausal patients fertility issues should be discussed as the agents used can cause a decrease in or, in some cases, loss of fertility.