Outcomes with allogeneic stem cell transplant using cryopreserved versus fresh hematopoietic progenitor cell products.

BACKGROUND: Allogeneic hematopoietic stem cell transplant (alloHSCT) is a mainstay of treatment for hematologic malignancies such as acute leukemias and aggressive lymphomas. Historically, fresh hematopoietic progenitor cell (HPC) products have been preferred to cryopreserved products (cryo-HPC) due to concerns of loss of stem cell viability and number with the cryopreservation procedure. OBJECTIVE: We aimed to analyze the outcomes of patients who received cryo-HPCs during the COVID-19 pandemic and compare this against historical cohorts that received fresh HPC. STUDY DESIGN: A retrospective chart review was conducted on all adult patients who received a peripheral blood alloHSCT in British Columbia, Canada between June 2017 and November 2021. Baseline characteristics, Kaplan-Meier (KM) overall survival (OS), engraftment, and incidences of acute and chronic graft versus host disease were compared between patients who received cryo-HPCs and fresh HPCs. Univariable analysis followed by multivariable analysis was performed using a backward stepwise selection procedure to generate predictors of OS, cumulative incidence of relapse (CIR), nonrelapse mortality (NRM), and primary and secondary graft failure. RESULTS: Three hundred eighty-three patients were included in the analysis, with cryo-HPC representing 40%. Median viability was higher in the fresh-HPC group at 99.2% (IQR 98.3-99.5) versus cryo-HPCs at 97.0% (96.0, 98.6) (P < 0.01). The 12-month actuarial survivals were 77% in the fresh HPC and 75% in the cryo-HPC groups (P = 0.21). There were no differences between cryo-HPCs and fresh HPCs on univariable analysis of OS, CIR, or NRM. There was a shorter median time to platelet engraftment in patients receiving fresh HPC at 17 days (IQR 16, 20) versus cryo-HPC at 21 days (IQR 18, 29), P < 0.001. There was a shorter median time to neutrophil engraftment in the fresh HPC group at 17 days (IQR 14, 20) versus 20 days (17, 23), P < 0.001. Cryo-HPC accounted for 5 out of 6 cases of primary graft failure (P = 0.04), and 3 out of five cases of secondary graft failure (P = 0.39). There were no significant differences in acute GVHD between the fresh HPC and cryo-HPC groups (P = 0.34). The incidence of moderate or severe chronic GVHD was 32% in the fresh-HPC group and 17% in the cryo-HPC group (P < 0.001). In multivariable analysis, cryopreservation did not emerge as an independent predictor of OS, CIR, NRM, primary GF or secondary GF. However, viability <90% on arrival at our center was a significant predictor of OS (HR 5.3, 2.3-12.3, P < 0.01), primary graft failure (OR 36.3, 5.4-210.2, P < 0.01), and secondary graft failure (OR 18.4, 1.7-121.1, P < 0.01). CONCLUSIONS: Patients who received cryo-HPCs had similar OS and relapse rates to those who received fresh-HPCs but typically took 2-3 days longer to achieve engraftment of platelets or neutrophils and were associated increased primary graft failure. However, after accounting for multiple variables, cryopreservation was no longer a significant predictor of survival or engraftment while viability <90% emerged as an important predictor of OS, primary graft failure, and secondary graft failure. If confirmed, this suggests that viability on arrival at the infusion center may be a good quality control indicator used to identify HPC products that may warrant recollection if the risk of graft failure is sufficiently increased.

Octopaminergic neurons have multiple targets in Drosophila larval mushroom body calyx and can modulate behavioral odor discrimination.

Discrimination of sensory signals is essential for an organism to form and retrieve memories of relevance in a given behavioral context. Sensory representations are modified dynamically by changes in behavioral state, facilitating context-dependent selection of behavior, through signals carried by noradrenergic input in mammals, or octopamine (OA) in insects. To understand the circuit mechanisms of this signaling, we characterized the function of two OA neurons, sVUM1 neurons, that originate in the subesophageal zone (SEZ) and target the input region of the memory center, the mushroom body (MB) calyx, in larval Drosophila We found that sVUM1 neurons target multiple neurons, including olfactory projection neurons (PNs), the inhibitory neuron APL, and a pair of extrinsic output neurons, but relatively few mushroom body intrinsic neurons, Kenyon cells. PN terminals carried the OA receptor Oamb, a Drosophila α1-adrenergic receptor ortholog. Using an odor discrimination learning paradigm, we showed that optogenetic activation of OA neurons compromised discrimination of similar odors but not learning ability. Our results suggest that sVUM1 neurons modify odor representations via multiple extrinsic inputs at the sensory input area to the MB olfactory learning circuit.

Patient-Reported Pain in Patients with Breast Cancer Who Receive Radiotherapy.

BACKGROUND: Patients who receive radiation treatment (RT) for breast cancer often report pain, which contributes negatively to quality of life (QoL). AIMS: To identify demographic, treatment, and disease characteristics associated with pain and changes in pain before and after RT using the Edmonton Symptom Assessment Scale (ESAS). DESIGN: Retrospective study. SETTINGS: Odette Cancer Centre. PARTICIPANTS: Patients diagnosed with nonmetastatic breast cancer from January 2011-June 2017 with at least one ESAS completed pre-RT and one completed post-RT. METHODS: Data on systemic treatment, radiation, patient demographics, and disease stage were extracted. To identify factors associated with pain before and after RT and changes in pain, univariate and multivariate general linear regression analysis were conducted. p < .05 was considered statistically significant. RESULTS: This study included 1,222 female patients with a mean age of 59 years. ESAS was completed an average of 28 days before RT (baseline) and 142 days after RT, respectively. In multivariable analysis, higher baseline pain scores were associated with having recently completed adjuvant chemotherapy (p = .002) and eventual receipt of locoregional (p = .026) or chest wall (p = .003) radiation. Adjuvant chemotherapy (p = .002) and chest wall radiation (p = .03), were associated with a significant reduction in pain score after radiotherapy, while locoregional RT was associated with a higher pain score after RT (p < .001). CONCLUSIONS: Patients with locoregional RT had higher baseline pain that remained elevated after RT completion and should be screened for pain and provided with pain management and support when necessary.

Self-reported pain in breast cancer patients receiving adjuvant radiotherapy.

PURPOSE: Breast cancer patients receiving radiotherapy (RT) commonly report pain, contributing to physical and emotional distress, and potentially resulting in poor quality of life. This study prospectively identified trends and risk factors in patient-reported pain associated with breast irradiation using the Edmonton Symptom Assessment Scale (ESAS) and a study-specific Skin Symptom Assessment (SSA). METHODS: Before RT and once per week during RT, patients completed the ESAS and SSA. Upon RT completion, patients were contacted via telephone to complete both assessments weekly for 6 weeks, and a final assessment was conducted 1-3 months post-RT. Only data from patients who had completed both assessments before, at least once during, and at least once after RT were included in our analysis. RESULTS: A total of 426 patients provided data for the analysis. Overall acute pain increased significantly at week 1-2 (p < 0.0001), week 5 (p = 0.0011), and at 1-3 months (p < 0.0001) post-RT compared with baseline, and acute breast pain increased significantly at week 1 (p < 0.001) and week 2 (p = 0.0002) post-RT compared with baseline. Previous chemotherapy (adjuvant or neoadjuvant) in mastectomy patients was associated with increased overall pain compared with mastectomy patients without previous chemotherapy (p = 0.017). Younger patients (40-49 or 50-59 years of age) reported more overall pain (p = 0.0001, p = 0.038) and breast pain (p = 0.0003, p = 0.0038) compared with patients ≥ 60 years of age. CONCLUSIONS: Patient-reported pain associated with breast irradiation peaked 1 week after RT completion. Our findings provide support for closer monitoring of acute pain associated with breast RT in younger patients.

Ultrasound-Guided Focused Ultrasound Treatment for Painful Bone Metastases: A Pilot Study.

Focused ultrasound (FUS) for palliation of bone metastases has typically been performed under magnetic resonance guidance. To address limitations of this approach, this pilot study evaluated a stand-alone, portable FUS device guided by diagnostic ultrasound alone (ultrasound [US]-guided FUS). Nine patients were treated; safety and efficacy were assessed for 10 d after the procedure, and medical charts were evaluated to assess durability of pain response. The procedure was safe and tolerable, with four patients reporting minor skin-related irritations. Average pain score decreased from 6.9 at baseline to 3.2 at day 10; analgesic use on average also decreased from baseline to day 10. Six patients had durable pain relief as assessed after the follow-up period. Our study provides evidence that US-guided FUS is a safe, tolerable and versatile procedure. It appears to be effective in achieving durable pain response in patients with painful bone metastases. Further research is required to refine the technology and optimize its efficacy.

Pain descriptors of taxane acute pain syndrome (TAPS) in breast cancer patients-a prospective clinical study.

BACKGROUND: Taxane acute pain syndrome (TAPS) is a clinically significant side-effect of taxane chemotherapy, often described as arthralgia and myalgia that occurs 2-3 days after infusion. The aim of this study was to assess pain descriptors used by patients during their experience of TAPS. METHODS: A clinical prospective cohort study was conducted on breast cancer patients who had not received prior chemotherapy and were asked to complete diaries on three consecutive docetaxel treatment cycles on days 1-7, 14, and 21 (acute phase). Questionnaires to assess pain severity, descriptors of pain, and the interference in activities due to pain were adapted from the Brief Pain Inventory and the McGill Pain Questionnaire. Telephone questionnaire follow-up was done at 1, 3, 6, 9, and 12 months following docetaxel (delayed phase). RESULTS: The most commonly used descriptor for acute and chronic pain was "aching" (90-96%). However, in the delayed phase of the study, "burning" (32-50%), "radiating" (39-48%), and "sharp" (40-69%) were used more often. In both acute and chronic pain phases, most patients experienced moderate/severe pain regardless of the location. Pain in cycle 1 was predictive of pain in subsequent taxane cycles (p < 0.0001). Pain in cycle 3 was predictive of chronic pain (p < 0.002). CONCLUSIONS: The descriptors used by patients experiencing chemotherapy-induced pain (ChIP) may be reflective of the underlying mechanisms. It is suspected that TAPS initiates as an acute inflammatory pain, which over time develops into neuropathic pain, known as chemotherapy-induced peripheral neuropathy (CIPN). However, the subjective pain experience varies from patient to patient.

Psychological morbidity in women diagnosed with ductal carcinoma in situ compared with women with early breast cancer receiving radiotherapy.

PURPOSE: Despite having an excellent prognosis, patients with ductal carcinoma in situ (DCIS) report significant anxiety and depression following diagnosis. This study evaluated psychological morbidity using the Edmonton Symptom Assessment Scale (ESAS) in patients with DCIS compared with women with early-stage invasive breast cancer (EIBC) receiving radiotherapy (RT). METHODS: We identified patients diagnosed with DCIS or EIBC (stage I or II breast cancer) from 2011 to 2017 who had at least one ESAS completed pre- and post-RT. Data on systemic treatment, radiation, patient demographics, and disease stage were extracted from existing databases. Psychological morbidity was evaluated through measurement of depression, anxiety, and overall wellbeing within the ESAS. The Wilcoxon rank-sum test or chi-square test was performed for continuous or categorical variables. RESULTS: This study included 137 women with DCIS and 963 women with EIBC. ESAS was completed on average 28 days before RT (baseline) and 142 days after RT. Baseline ESAS scores showed significantly higher rates of depression among women with EIBC compared with those with DCIS (p = 0.006). Patients with EIBC also reported higher levels of anxiety and lower overall wellbeing than patients with DCIS, but this difference was not statistically significant. Post-RT ESAS scores showed significantly higher anxiety in patients with EIBC compared with DCIS (p = 0.049). Post-RT measures of anxiety and overall wellbeing were higher in patients with EIBC but differences were not statistically significant. CONCLUSION: Women with DCIS experience relatively less psychological morbidity than women with EIBC, pre- and post-RT.

Fractionation in adjuvant radiotherapy for invasive breast cancer and ductal carcinoma in situ in Ontario, Canada from 2009 to 2015.

The use of hypofractionated radiotherapy (HFRT) in patients with breast cancer and ductal carcinoma in situ (DCIS) in Ontario, Canada, from 2009 to 2015 was reported. A retrospective cohort study was conducted using data from the Institute for Clinical Evaluative Sciences (ICES). Patients with a breast cancer or DCIS diagnosis between 2009 and 2015 who received adjuvant breast or chest wall radiation were included. Trends in HFRT use (≤16 fractions) and factors associated with HFRT use in a multivariable logistic regression model with physician-level random effect were reported. The approximate number of hours that could be saved if all patients were to receive HFRT was calculated. A total of 42 072 patients were included. All included characteristics were significantly associated with HFRT use. Hypofractionated radiotherapy use in patients with breast cancer and DCIS increased to around 75% in 2015. In stage I/II patients with mastectomy and chest wall radiation, HFRT use increased to 40% in 2015. Hypofractionated radiotherapy use in patients with regional nodal radiation or reconstruction has increased but remains under 20%. For breast cancer patients with breast-conserving surgery (BCS) and breast radiation, 56 265 visits corresponding to 7200 hours of treatment or 3500 additional HFRT courses could have been saved. In conclusion, HFRT use in Ontario has increased in all patient populations but is nonuniform among physicians and institutions. Use of HFRT in chest wall and regional nodal radiation remains relatively lower than in breast cancer and DCIS patients with BCS.

Thermal Therapy With a Fully Electronically Steerable HIFU Phased Array Using Ultrasound Guidance and Local Harmonic Motion Monitoring.

The method of localized harmonic motion (LHM) monitoring has been proposed as an ultrasound-based monitoring technique for in vivo real-time ultrasound-guidance during thermal surgery. OBJECTIVE: The focus of this paper is to study the performance of LHM monitoring in vivo in order to assess the tissue coagulation during ultrasound surgery of bone metastases. This is done through a pre-clinical study on large scale animals (pigs) as well as a first-in-human pilot study, using a hand held ultrasound-guided HIFU phased array. METHODS: A flat, fully steerable HIFU phased array system (1024 elements, 100 mm diameter, 516 kHz), in combination with a co-aligned 64 element imaging system, is used to perform thermal surgery and monitor tissue coagulation using the LHM technique. The in vivo experiments are conducted using thirteen animals, followed by a first-in-human pilot study in which nine patients are enrolled. RESULTS: The pre-clinical results show that the LHM monitoring method is able to detect about 80% of the observed coagulated tissue volumes visible in dissection. In the pilot study, six out of nine patients have durable pain reduction with good correlation observed from LHM detections. CONCLUSION: In general, the results suggest that the LHM monitoring performance is promising in detecting thermal tissue coagulation during focused ultrasound surgery in tissues close to the bone. SIGNIFICANCE: The LHM technique can offer a very accessible and cost-efficient monitoring solution during ultrasound surgery within a clinical setting.

Symptom clusters in patients with breast cancer receiving radiation therapy.

PURPOSE: Symptoms experienced by breast cancer patients often cluster together in groups known as "symptom clusters". The aim was to determine the symptom clusters in women with non-metastatic breast cancer treated by radiation therapy (RT). METHODS: Edmonton Symptom Assessment Scale (ESAS) scores were taken from breast cancer patients receiving RT before, at completion of RT, and after RT. Exploratory factor analysis (EFA), principal component analysis (PCA), and hierarchical cluster analysis (HCA) were used to identify symptom clusters among the nine ESAS items at all three time points. RESULTS: This study included 1224 patients. The PCA and EFA identified the same two symptom clusters before the start of RT: 1) pain, tiredness, nausea, drowsiness, appetite, and dyspnea; 2) depression, anxiety, and wellbeing. The HCA further split the symptoms into three clusters. Wellbeing, depression, and anxiety consistently clustered together. Among the ESAS scores collected at the end of and after RT, each statistical method identified different symptom clusters. For the symptom clusters experienced at the end of RT, the following symptoms were always in the same cluster: wellbeing, depression, and anxiety; nausea and appetite; drowsiness and dyspnea. Following RT, depression and anxiety consistently clustered together, with nausea and appetite in a second cluster. CONCLUSION: Among the symptom clusters derived before, at the end of RT, and after RT, the following symptoms consistently presented together: depression and anxiety, nausea and appetite, pain and tiredness, and drowsiness, dyspnea, and tiredness. Understanding symptom clusters in this population can improve management of symptoms.

Seasonal fluctuations in psychological distress amongst women diagnosed with early breast cancer receiving radiotherapy.

OBJECTIVE: Seasonal effects on patients diagnosed with depression/anxiety-related psychological disorders have varying impacts on symptom severity. Seasonal changes in psychological distress may be due to decreased daylight exposure during the fall/winter seasons. Patients receiving radiation therapy (RT) for early-stage invasive breast cancer (EIBC) are at high risk for developing depressive symptoms. Of interest is whether seasonal factors influence the psychological symptoms of patients being treated for EIBC. METHODS: Patients treated with RT for EIBC between January 2011 and June 2017 were identified. Patients who completed at least one Edmonton Symptom Assessment Scale (ESAS-r) pre-RT and post-RT were included in our analysis. Patients receiving RT during the autumn and winter (November-March) were compared with patients receiving RT during the spring and summer (April-August). Psychological distress was evaluated based on patient-reported depression, anxiety, and overall wellbeing on the ESAS-r. Data on systemic treatment and radiation were extracted from existing databases. RESULTS: Eight-four patients treated with RT in spring/summer and 102 patients treated with RT in autumn/winter were included. Patients receiving RT during spring/summer had better wellness score prior to RT, compared with those receiving RT during winter/autumn (P = .03). However, patients receiving RT in the spring/summer had worse symptom trajectories across three domains of depression, anxiety, and wellbeing (P = .03, P = .008, and P < .0001, respectively). CONCLUSIONS: Seasonality influenced the symptoms reported by patients with EIBC receiving RT. Future studies are needed to understand when during treatment patients are at highest risk for psychological distress and how seasonality may influence high-risk periods.

Patient-reported fatigue in breast cancer patients receiving radiation therapy.

PURPOSE: Fatigue or tiredness is one of the most commonly reported symptoms in breast cancer patients treated with radiation therapy (RT). This study aimed to identify characteristics associated with fatigue in breast cancer patients receiving adjuvant RT. METHODS: Patients with non-metastatic breast cancer receiving RT at the Odette Cancer Centre from 2011 to 2017 were included in our study if they completed at least one ESAS pre- and post-RT. Information regarding patient, disease and treatment characteristics was retrieved from chart review. To identify variables associated with fatigue scores pre-RT, post-RT and changes in fatigue scores, a univariate and multivariate general linear regression analysis was conducted; p < 0.05 was considered statistically significant. RESULTS: Our study included 1223 female patients (mean age 59 years old) who completed ESAS on average 28 days before, and 142 days after RT. In multivariate analysis, higher baseline fatigue scores were found in women with higher disease stages (p = 0.001), and those who receive locoregional radiation (p < 0.001). No variables were significantly associated with post-RT fatigue scores. While adjuvant chemotherapy and locoregional RT were associated with higher baseline scores in univariate analysis, in multivariate analysis, they were associated with significant reduction in fatigue post-RT (p = 0.01, p = 0.007 respectively). CONCLUSIONS: Fatigue is associated with higher disease stage and receipt of locoregional radiation. While the relationship between anxiety or depressive symptoms and fatigue is well-established, a major gap exists in our understanding of its etiology and treatment; further investigation to address this can better improve patient quality of life.

Symptoms Predictive of Overall Quality of Life Using the Edmonton Symptom Assessment Scale in Breast Cancer Patients Receiving Radiotherapy.

BACKGROUND: Breast cancer patients often experience multiple symptoms that negatively affect quality of life (QOL). Patient-reported scores on symptom screening tools are used by health care professionals to manage QOL. We aimed to examine which symptoms from the Edmonton Symptom Assessment Scale (ESAS) were most predictive of overall well-being (QOL) in breast cancer patients over the course of radiotherapy (RT). PATIENTS AND METHODS: ESAS results completed before, at the end of, and after RT were obtained from all nonmetastatic breast cancer patients. Univariate and multivariable (backward stepwise selection) linear regression analyses were applied to select the most significant ESAS symptoms or treatment variables related to overall QOL at all 3 time points. RESULTS: A total of 1224 patients were included in the study. Before RT, multivariable analysis identified 5 symptoms that were significantly associated with overall QOL: pain, tiredness, anxiety, depression, and loss of appetite. At the end of RT, pain, tiredness, and anxiety were the most significant predictors of QOL. After RT, 6 symptoms were found to have the strongest correlation with QOL: pain, tiredness, anxiety, depression, loss of appetite, and drowsiness. At each time point, patients with higher scores for the identified significant symptoms were likely to have a worse overall QOL. CONCLUSION: Of the ESAS symptoms identified as significant predictors of QOL, pain, tiredness, and anxiety correlated with overall well-being at all time points. Special attention should be paid to manage symptoms that are most predictive of overall QOL in order to ensure optimal symptom management in breast cancer patients receiving RT.

Mepitel Film and Mepilex Lite for the prophylaxis and treatment of skin toxicities from breast radiation.

Despite the prevalence of radiation dermatitis in breast cancer patients, current practice guidelines for its treatment are limited. We aimed to discuss the quality of evidence for the barrier-forming Mepitel Film for prophylaxis of radiation dermatitis, and argue for further investigation into evidence-based management of skin toxicities. Two studies assessing Mepitel Film were critically evaluated. Both reported that Mepitel Film decreased radiation dermatitis; moreover, patient-reported outcomes significantly favoured Mepitel Film. However, there has not been global adoption of barrier-forming films such as Mepitel, in part due to the absence of multi-centred randomised trials and the heterogeneity of study designs.

Evaluation of the 3-day recall period for the Functional Life Index-Emesis (FLIE).

BACKGROUND: Nausea and vomiting are commonly experienced by cancer patients, and can be assessed by the Functional Life Index-Emesis (FLIE) instrument which employs a three-day recall period. However, it is unknown whether patients' responses to the FLIE better correlate with the average or the worst symptom severity of the recall period, or the severity of an individual day. METHODS: Patients receiving emetogenic radiotherapy for painful bone metastases who were enrolled in one of three trials for anti-emetic medications (ondansetron, aprepitant/granisetron, or palonosetron) completed the FLIE at baseline, and days 3, 5, 7, or 10 during treatment and follow-up. The concordance correlation coefficient (rc) was calculated between FLIE overall nausea and vomiting and daily nausea, vomiting, and quality of life (QoL) using the average responses of the 3-day recall period and with each of the three days' responses. RESULTS: Responses from eighty-nine patients who experienced nausea or vomiting were analysed. The highest concordance for FLIE nausea was with the 3-day average [during treatment: rc =0.698, 95% confidence interval (CI): 0.495, 0.829; follow-up: rc =0.821, 95% CI: 0.711, 0.892]. FLIE vomiting had the highest concordance with worst day vomiting (during treatment, rc =0.310, 95% CI: 0.194, 0.417) or two day-prior vomiting (follow-up, rc =0.902, 95% CI: 0.832, 0.944). FLIE nausea and vomiting had inconsistent concordances with daily assessments of QoL. CONCLUSIONS: Responses to the FLIE questionnaire are most representative of average nausea severity. Larger cohorts to validate these findings are warranted to address the lack of power in this present study and to confirm the wording and justification of a three-day recall period for the FLIE.

Management of radiation-induced nausea and vomiting with palonosetron in patients with pre-existing emesis: a pilot study.

BACKGROUND: Approved almost 15 years ago for use in the chemotherapy setting, palonosetron, a 2nd generation 5-hydroxtryptamine 3 receptor antagonist (5-HT3 RA), has demonstrated efficacy in preventing chemotherapy-induced nausea and vomiting. However, its utility in the prophylaxis and treatment of radiation-induced nausea and vomiting (RINV) has yet to be evaluated. In this pilot study, we investigated the rates of control in RINV in patients with pre-existing emesis. METHODS: Patients with pre-existing emesis undergoing palliative radiotherapy to sites with emetic risk were prescribed palonosetron 0.5 mg before the start of radiation treatment, and every other day until completion of treatment. Patients were followed up in acute (day 1 of treatment to day 1 after treatment) and delayed phases (days 2-10 after treatment). Prophylaxis and rescue (PR) was defined as a decrease in anti-emetic use, or episodes of nausea and/or vomiting from baseline. Complete prophylaxis (CP) was defined as no increase in anti-emetic use, or episodes of nausea and/or vomiting. Secondary endpoints included control of nausea and quality of life (QOL), as assessed with the Functional Living Index-Emesis and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15 Palliative. RESULTS: Fourteen patients were enrolled. Rates of control were higher in the acute phase (n=14) for nausea (PR =42.9%, CP =42.9%) and vomiting (PR =21.4%, CP =71.4%) compared to the delayed phase (n=13) for nausea (PR =42.9%, CP =7.7%) and vomiting (PR =15.4%, CP =53.8%). CONCLUSIONS: Palonosetron appears to be safe and patients with pre-existing emesis receiving palliative radiotherapy. More studies are needed to investigate its efficacy in this patient population.

Predictive biomarkers of chemotherapy-induced peripheral neuropathy: a review.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of taxane treatment during chemotherapy. Identifying predictive biomarkers of CIPN would allow physicians to alter treatment given to patients according to a personal risk of developing this condition. The current literature on CIPN biomarkers is reviewed, identifying biomarkers which have been found to be significantly related to CIPN. Three genetic biomarkers are identified (ARHGEF10 rs9657362, CYP2C8 rs11572080/rs10509681 and FGD4 rs10771973) which have been found to act as predictive CIPN biomarkers in multiple studies. Possible mechanisms underlying the relationship between these single nucleotide polymorphisms and CIPN development are explored. The biomarkers identified in this study should be investigated further to generate predictive biomarkers that may be used in a clinical setting.

Impact of radiation-induced nausea and vomiting on quality of life.

PURPOSE: Radiotherapy-induced nausea and vomiting is a common side effect of radiotherapy. It is well-established that nausea and vomiting have a negative impact on quality of life, but the relative influence of each of symptom is infrequently reported. This study aimed to compare the effects of nausea and vomiting on quality of life in cancer patients receiving palliative radiotherapy. METHODS: The Functional Living Index-Emesis (FLIE) is a quality of life questionnaire developed in the chemotherapy-induced nausea and vomiting setting. The FLIE consists of 18 questions, half of which address nausea and half of which address vomiting. Three prospective studies on the efficacy of various anti-emetic medications conducted at our center used the FLIE to assess radiotherapy-induced nausea and vomiting at various time points during and after palliative radiotherapy. FLIE data from these three studies were combined for the present analysis. Univariate and multivariate analyses were conducted to assess the relationships between nausea and vomiting, time of FLIE completion, and patient-reported quality of life. RESULTS: Nausea and vomiting scores both decreased patients' quality of life. Multivariate modeling showed that both symptoms significantly influenced patients' ability to enjoy meals. Nausea was also associated with increased hardship for the patient, while vomiting imposed more difficulty on the patients' loved ones. CONCLUSIONS: Nausea and vomiting both significantly influence quality of life. Nausea seems to impact the patient more directly, whereas vomiting affects those closest to the patient.

Symptom clusters using the EORTC QLQ-C15-PAL in palliative radiotherapy.

BACKGROUND: Patients with advanced cancer often experience a multitude of symptoms. Due to the potential interrelation of symptoms, symptom clusters of 2 or more concurrent symptoms have been advocated for use in the palliative setting to provide better management of symptoms. METHODS: The principal component analysis (PCA), exploratory factor analysis (EFA) and hierarchal cluster analysis (HCA) were conducted on responses to items 1-14 in the European Organisation for Research and Treatment of Cancer Quality of Life-C15-Palliative (EORTC QLQ-C15-PAL) at baseline and days 5 and 10 following RT. RESULTS: There was complete data for 109, 90 and 87 patients at baseline, day 5 and day 10 respectively. The average age was 72 years. The most common site of primary was the prostate (36.7%), and almost all patients presented with bone metastases (95.4%). Analyses identified 2-4 clusters at each interval. From baseline to day 10 follow-up, across all analyses, items associated with physical functioning clustered consistently with shortness of breath. Pain and pain interference clustered with nausea at baseline; and with sleep at both follow-up intervals. Cronbach's alpha values for the clusters ranged from 0.53 to 0.90. CONCLUSIONS: Fluctuation of symptom clusters was observed in a short time frame following palliative RT. Although clusters were dynamic, several items tended to cluster together. Further research is required to validate these clusters.

A pilot study with palonosetron in the prophylaxis of radiation-induced nausea and vomiting.

BACKGROUND: Palonosetron is an effective antiemetic in chemotherapy-induced nausea and vomiting (CINV), but has yet to be studied in the radiation setting. The purpose of the present study was to investigate the efficacy and safety of palonosetron in the prophylaxis of radiation-induced nausea and vomiting (RINV). METHODS: Patients without existing nausea and vomiting undergoing palliative radiotherapy to sites with emetic risk were prescribed palonosetron 0.5 mg orally before the start of radiation treatment, and every other day until completion of treatment. Patients were followed up in acute (day 1 of treatment to day 1 after treatment) and delayed phases (days 2-10 after treatment). The primary endpoint was control of vomiting. Complete control was defined as no use of rescue medication and no episodes of nausea or vomiting. Secondary endpoints included control of nausea and quality of life (QOL). QOL was assessed with the Functional Living Index-Emesis and the European Organisation for Research and Treatment of Cancer QOL Questionnaire-Core 15 Palliative (C15-PAL). RESULTS: In all evaluable patients (n=75), complete control of vomiting was 93.3% in the acute phase and 93.2% in the delayed phase. Complete control of nausea was 74.7% in the acute phase and 74.0% in the delayed phase. CONCLUSIONS: Results suggest improved control in RINV compared to historical reports with first generation serotonin receptor antagonists (RA). A randomized study will be needed to confirm this finding.