bluuebunny/crossref_metadata_2025 huggingface dataset:
Vemurafenib-associated bullous DRESS syndrome: A very severe cutaneous reaction.
Authors: Gey Aurelia , Jouary Thomas , Mateus Christine , Robert Caroline , Perro Gerard , Milpied Brigitte
Published: March 2020

e20041

Background: Vemurafenib, a selective BRAF inhibitor, has recently demonstrated improved overall survival in metastatic melanoma. Frequent cutaneous side effects have been reported with vemurafenib, mostly non severe. We report the first case of bullous DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) related to vemurafenib. Methods: Case report: A 69 year old man presented with a BRAF mutated multimetasatic melanoma. Vemurafenib, 960 mg orally twice daily, was started in August 2012. Treatment was discontinued 1 month later because of a grade 2 rash and nausea. Treatment was re-introduced 10 days later with reduction of the dose, 480 mg twice daily. Four days later, the patient had fever, diffuse rash with pustular blistering and eosinophilia up to 1000/mm3. Despite withdrawal of vemurafenib, skin detachment appeared with extension on more than 90% of the body surface and erosions involving oral and genital mucosa requiring admission in intensive care burn unit. A skin biopsy revealed infiltration of the epidermis and the upper dermis with lymphocytic lichenoid vasculitis and focal necrolytic keratinocytes. Intravenous steroids were provided and lesions rapidly resolved with total epithelisation within 15 days. To date, the patient is still alive and undergoes active palliative care. Results: Discussion: DRESS syndrome is a severe drug reaction defined as an acute and severe heterogeneous rash with general symptoms, biological abnormalities, and visceral damages. It occurs from 3 to 6 weeks after drug administration. With a Kardaun score of 4, there were several arguments for a DRESS syndrome to vemurafenib: diffuse and acute rash occurring after 5 weeks of treatment, initial eosinophilia, aggravation of skin lesions despite withdrawal of the culprit drug, histological features and rapid improvement after steroid treatment. With more than 90% of body surface skin detachment, requiring treatment in burn center, the diagnosis was a very severe bullous DRESS syndrome. Vemurafenib was the only culprit drug in our case, as the patient did not received any other drug. Conclusions: Though toxic epidermal necrolysis has been reported yet with vemurafenib, no case of DRESS syndrome has been described to date.
Effect of microRNA-206 on G1 arrest by inhibition of CDK4, cyclin C, and cyclin D in melanoma cells.
Authors: Georgantas Robert W , Streicher Katie , Luo Xiaobing , Zhu Wei , Liu Zheng , Brohawn Philip , Morehouse Chris , Higgs Brandon W , Richman Laura , Jallal Bahija , Yao Yihong , Ranade Koustubh
Published: March 2020

e20047

Background: MiR-206 has been implicated in a large number of cancers. However, its role in tumor biology is unknown and its biological function has yet to be fully characterized. To examine the role of miR-206 in cancer, we examined the expression of miR-206 in melanoma and identified potential target transcriptss that could be important for the progression of this disease. Methods: Using quantitative RT-PCR we compared expression of 364 microRNAs in melanoma skin biopsies skin from normal donors, melanoma cell lines, and normal melanocytes. The effects of miR-206 on cell growth, apoptosis, and cellular migration/invasion were determined using in vitro assays comparing melanoma cell lines to normal melanocytes. Putative mRNA targets of miR-206 were bioinfomatically identified, and empirically tested by luciferase-3’UTR reporter assays. The effect of miR-206 on the cell cycle of melanoma cells was assayed by flow cytometry. Results: Expression profiling of microRNAs in melanoma lesional skin biopsies compared to normal donor skin biopsies revealed numerous differentially regulated miRs. One such microRNA, miR-206, was significantly highly down-regulated in melanoma biopsies (-75.4-fold, p=1.7x10-4) compared to normal skin and normal melanocytes. Functional analysis showed that miR-206 substantially reduced growth and migration/invasion of multiple melanoma cell lines. Bioinformatic analysis identified the cell cycle genes CDK2, CDK4, Cyclin C, and Cyclin D1 as strong candidate mRNA targets of miR-206. Luciferase reporter gene assays revealed that miR-206 inhibits translation of CDK4, Cyclin D1, and Cyclin C. Consistent with this inhibition of CDK4 and Cyclin D1, miR-206 transfection induced robust G1 arrest in multiple melanoma cell lines. Conclusions: MiR-206 expression was decreased in melanoma tissue and cell lines compared to normal skin and melanocytes, respectively. Inhibition of Cyclin C, Cyclin D1 and CDK4 by miR-206 highlights its role in regulating cell cycle progression, a key aspect of melanoma progression. These observations support miR-206 as a potential tumor suppressor in melanoma, and possibly other cancers.
Outcomes and clinical markers associated with benefit from ipilimumab (Ipi) in patients with advanced melanoma: A retrospective single-institution study.
Authors: Zimmerman Zachary Franklin , Storer Barry , Godara Amandeep , Thompson John A. , Margolin Kim Allyson , Tykodi Scott S. , Rockhill Jason K. , Lee Sylvia Mina , Brown Anna , Patel Amila , Smith Jon , Bhatia Shailender
Published: March 2020

e20048

Background: Ipi (anti-CTLA4 antibody) is associated with improved survival and durable responses in a subset of melanoma pts. However, the optimal dose and schedule remain unclear and an unmet need to identify predictors of clinical benefit exists. This retrospective study of pts at the University of Washington aims at gaining further insight into these questions. Methods: Efficacy and safety outcomes and baseline characteristics of 126 pts receiving single agent Ipi from 2006-2012 were subjected to univariate analysis. Efficacy endpoints included OS, PFS, ORR and Duration of Clinical Benefit (DCB) defined as the time from Ipi initiation until documented progression or change in therapy (to capture outcomes on non-trial pts). Immune-related adverse events (IRAEs), absolute lymphocyte count (ALC), concordance of disease response by metastatic site, and use of radiation therapy (RT) were also analyzed. Results: The median age was 57.7 yrs. The 3 mg/kg (N=84; 67%) and 10 mg/kg (N=42; 33%) cohorts matched well for standard prognostic criteria. The efficacy endpoints, including OS, PFS, DCB, and ORR (see table) were not significantly different for the 3 mg/kg and 10 mg/kg cohorts. However, grade III/IV IRAEs were more frequent in the 10 mg/kg group (33% vs 17%, p=0.04). There was a significant correlation between efficacy outcomes and development of IRAEs (see table). Baseline ALC or changes in ALC at 7 weeks post-therapy and concurrent RT administration did not significantly correlate with improved outcomes. Responses were concordant between CNS and non-CNS sites. Conclusions: Our data supports the currently approved dose of 3mg/kg. The development of IRAEs was significantly associated with clinical benefit and further confirmation of this association is warranted. Results of other exploratory analyses will be presented at the meeting. [Table: see text]
Maintenance interleukin-2 (IL-2) and sargramostim (GM-CSF) following high-dose IL-2 (HD IL-2) therapy for metastatic melanoma.
Authors: Chu Melinda Bernabe , Fesler Mark , Armbrecht Eric , Fosko Scott , Hsueh Eddy C. , Richart John M.
Published: March 2020

e20049

Background: At our institution, patients with metastatic melanoma who achieve partial response (PR) to HD IL-2 therapy undergo monthly maintenance treatment with IL-2 and GM-CSF with the thought that the continuous stimulation of the immune system may improve response. Our aim was to describe our experience with maintenance treatment following HD IL-2 therapy. Methods: A retrospective chart review was performed on patients with metastatic melanoma seen at Saint Louis University from January 1999-June 2011 who were partial responders to HD IL-2 therapy (720,000 IU/kg per dose intravenously; 14 doses, 2 cycles per course, maximum 2 courses) that received maintenance IL-2 therapy (continuous 42 hour infusion of three consecutive doses of 18,000,000 IU/m2 over 6, 12 hours, then 24 hours) and GM-CSF (daily subcutaneous injection of 125 mcg/m2 for 3 days) every 4 weeks for 13 cycles or until disease progression. Duration of response for this cohort was compared to established data for partial responders using the Mann-Whitney test. Results: Five patients were included in the analysis. Median duration of response was 9 months (3.9-53.4 months). Median overall survival was 20.6 months (15-53.4+ months). One patient who initially showed PR to HD IL-2 therapy converted to complete response during maintenance IL-2 and has the longest duration of response in the study dataset. Duration of response for the maintenance group (9 months) was longer than a benchmark of 5.9 months as reported in the literature and package insert for partial responders to HD IL-2 without maintenance therapy, p = 0.068. Conclusions: Subjects who received maintenance IL-2 and GM-CSF therapy had a longer duration of response compared to previous reports, which trended toward statistical significance in this small sample. Maintenance IL-2 and GM-CSF after HD IL-2 therapy may help to prolong partial response, possibly lead to conversion to complete response and is worthy of additional study.
The PI3K inhibitor BKM120 has potent antitumor activity in melanoma brain metastases in vitro and in vivo.
Authors: Meier Friedegund Elke , Niessner Heike , Schmitz Jennifer , Schmid Andreas , Calaminus Carsten , Pichler Bernd , Forschner Andrea , Flaherty Keith , Honegger Juergen Bernd , Dummer Reinhard , Tabatabai Ghazaleh , Weide Benjamin , Eigentler Thomas K. , Schadendorf Dirk , Quintanilla-Fend Leticia , Garbe Claus
Published: March 2020

e20050

Background: In melanoma, the RAF-MEK-ERK and PI3K-AKT signaling pathways play a major role in melanoma progression and drug resistance. On the basis of significant improvement in overall survival, the BRAF inhibitor vemurafenib gained FDA approval for the treatment of patients with metastatic BRAFV600E mutated melanoma. However, vemurafenib appears to be less effective in melanoma brain metastases, and brain metastases are the most common cause of death in patients with metastatic melanoma. In our previous study we reported that the AKT survival pathway is hyperactivated in melanoma brain metastases. Methods: The current study aims to investigate the mechanisms of AKT hyperactivation and the antitumor activity of the PI3K inhibitor BKM120 in melanoma brain metastases in vitro and in vivo. Results: To simulate the tumor environment of brain metastases and extracerebral metastases, brain and matched extracerebral metastatic melanoma cells were stimulated by astrocyte- and fibroblast-conditioned medium, respectively. Both brain and extracerebral metastatic melanoma cells stimulated by astrocyte-conditioned medium showed higher AKT activation and invasiveness in a transwell matrigel invasion assay than cells stimulated by fibroblast-conditioned medium. The PI3K inhibitor BKM120 inhibited the phosphorylation of AKT and the growth of >10 newly isolated cell lines derived from melanoma brain metastases achieving growth inhibition rates of up to 80%. These effects did not depend on BRAF, NRAS or KIT mutation status. Furthermore, BKM120 potently induced apoptosis in brain metastatic melanoma cells and significantly inhibited the tumor growth of human brain metastatic melanoma cells in the brain of nude mice as shown by MRI scans. Conclusions: Brain-derived factors induce hyperactivation of the AKT survival pathway and promote invasiveness and drug resistance of melanoma cells in the brain. The PI3K inhibitor BKM120 inhibits activation of the AKT survival pathway and demonstrates potent antitumor activity in melanoma brain metastases in vitro and in vivo.
Circumvent anxiety of patients (CAP) while receiving chemotherapy at one-day hospital.
Authors: Kattan Joseph Gergi , Daher Alain , Assaker Lama jaoudat , Jreige Yolla Tanios , Aintouri Rachide Jamil , Eid Rouba
Published: March 2020

e20500

Background: Transforming patient anxiety to comfort during chemotherapy delivery is the desire of every cancer care givers. For the first time, a beauty clinic services are offered to adult cancer patients, while receiving one-day chemotherapy. Methods: One-day unit at Saint Joseph hospital is an independent department including 12 beds and serving around 160 chemotherapy sessions per month. A professional physiotherapist in beauty care and relaxation massage offers her services for every patient during 15 minutes session at his own bed. CAP program was approved by Saint Joseph ethical committee and supported by Jane Nassar institute. Evaluation questionnaires were filled by randomly selected patients. Results: CAP program was initiated in August 2012. Around 10 patients per day were included. 90% of our patients welcome the program and participate. The majority of patients who refused participation at the first visit accept it during the second session. Men choose hands or feet relaxation massage and women usually face beauty care. 22 patients were randomly selected to fill the CAP-evaluation questionnaire. Among these 22 patients, 2 (9%) refused to participate in the program, one of them did not have a clear reason, the other attributed to a state of uncomfortable and depression. Among the 20 who participated, 90% had at least two sessions, 100% would advise other patients to participate, 95% of them believe that this service adds an advantage to delivered care and provides a restful atmosphere, and all of them encourage the department to continue to provide this service. Conclusions: Psychosocial support is almost lacking in the management of our patients leading to increase their anxiety while receiving chemotherapy. CAP program represents a unique experience and temptation in adult patients to circumvent their anxiety.
Is routine administration of standardized questionnaires that assess aspects of patients’ quality of life justified in medical oncology clinics?
Authors: Al-Saleh Khalid A.
Published: March 2020

e20501

Background: increasing interest in the Quality of Life outcomes in cancer patients led to increase implementation of their use in routine clinical practice. The aim of this study is to review the scientific evidence behind recommending the use of quality of life (QoL) scales routinely in outpatient evaluation. Methods: systematic review for all published randomized controlled trials in English language between January 1, 1990 till December 1, 2010. Out of 479 articles (468 identified by electronic search + 11 articles identified by manual search), six trials satisfied the eligibility criteria: 1) the study was a randomized controlled trial (RCT) with randomization of patients or health care providers; 2) the findings of the administered questionnaire or scale (the intervention) were given to health care provider, and compared to standard care with no questionnaire administered (the control); 3) study was conducted in outpatient oncology clinics; and 4) an outcome was measured that related to i) QoL improvement, ii) reduction in morbidity, iii) reduction in stress for the patients, iv) improvement in communication between patients and health care provider, or v) improved patient satisfaction. Assessment for the quality of the study was done using the GRADE methodology. Results: serious methodological issues were affecting most of the trials. Overall the evaluation of the quality of the evidence from these identified trials suggests that there is a weak recommendation to use QoL scales in routine oncology practice to improve communication between physicians and patients. Conclusions: The routine use of such tools in the outpatient settings at improving the patient outcome or satisfaction cannot be recommended based on the available evidence. The potential harm with the excess use of resources needed to implement, collect, store, analyse, and present such data to health care providers should be also considered. Further research and better designed trials is required using recent methodological techniques (such as item-response theory based questionnaire and cluster randomization) might help to reach an answer to this question.
Personality traits in Turkish patients with cancer.
Authors: Turhal Nazim S. , Satici Celal , Cinar Caner , Kinar Abdullah , Demirhan Salih
Published: March 2020

e20502

Background: This study was planned to investigate the personality traits of cancer patients in different treatment settings, and to correlate the demographics with the personality features. Methods: A total of 237 patients referred either to Marmara University School of Medicine (MUSM) Oncology Outpatient Unit or to the private office of the faculty between March 10th and April 22nd, 2010 were enrolled in the study. Big Five Mini Test was used to evaluate the 40 personality traits filled by patients. Results: The study group consisted of 98 males (41.35%) and 139 females (58.65%) with a mean age of 51. Out of 237 patients, 73.9% had an educational level beyond the junior high school, and 47.3% of all patients reported a positive family history for cancer. A significant difference in terms of reconcilability, extraversion, and responsibility was observed between patients admitting to the university outpatient clinic and the private office (p<0.05). Reconcilability and extraversion were found to differ between genders significantly (p<0.05). The description of the patient by him/herself or by its relatives displayed a significant difference in terms of openness (p<0.05). Parameters such as educational level, family history of cancer, age and marital status showed no relevance with their characters. No discordance was observed between the self-analysis of the patient and the patient’s relatives. Conclusions: This is the first such study conducted in Turkish cancer patients and they found to be typically highly reconcilable and responsible, moderately stable, open and extraverted.
NK1 receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting: An updated meta-analysis.
Authors: dos Santos Lucas Vieira , Brunetto Andre Tesainer , Sasse Andre Deeke , Souza Fabiano Hahn , Lima Joao Paulo
Published: March 2020

e20506

Background: We have previously shown (dos Santos JNCI 2012) that NK1 receptor antagonists (NK1RA), such as aprepitant and casopitant, improve chemotherapy-induced nausea and vomiting (CINV) at the cost of increasing severe infection risk. Herein, we update our results. Methods: We searched MEDLINE, EMBASE, CENTRAL and meeting proceedings to identify randomized controlled trials (RCTs) comparing standard antiemetic therapy (dexamethasone + 5-HT3R inhibitors) versus NK1RA plus standard therapy for CINV prevention. Complete response (CR) was defined as absence of emesis and rescue therapy. The endpoints were CR post-chemotherapy in the overall phase (first 120 hours), CR in the acute phase (first 24 hours), and the delayed phase (24–120 hours), nausea, and toxicity. Subgroup analyses evaluated the type of NK1RA, the emetogenic potential of the chemotherapy, and prolonged use of 5-HT3R inhibitor. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Results: A total of 20 trials (9,935 patients) were included. NK1RA increased CR rate and nausea in all phases and subgroups. The CR in overall phase improved from 56% to 72% (OR = 0.52, 95% CI = 0.46 to 0.59, P < .00001, NNT=6). The side effects of NK1RA followed our previous report: the severe infection rate increased from 2.4% to 5.6% in the NK1RA group (four trials, 1656 patients; OR = 2.87; 95% CI = 1.58 to 5.19, P = .0005, NNH=31). Conclusions: NK1RA consistently improve CINV control in the acute, delayed, and overall phases, either for moderately or highly emetogenic chemotherapy regimens. Their use might be associated with increased infection rate, and a patient-level meta-analysis is warranted to clarify this safety issue.
Quality of life and psychosocial distress in young women with advanced breast cancer.
Authors: Seah Davinia Shien , Gelber Shari , Ruddy Kathryn Jean , Tamimi Rulla M. , Schapira Lidia , Come Steven E. , Meyer Meghan E , Larsen Bryce G. , Winer Eric P. , Partridge Ann
Published: March 2020

e20508

Background: Little is known about the quality of life (QOL), prevalence and predictors of psychosocial distress in young women with advanced breast cancer (ABC). Methods: As part of an ongoing longitudinal multi-center study of women aged < 40 with newly diagnosed breast cancer, we identified women with ABC. Using baseline survey and medical chart data, we assessed QOL (measured by the Medical Outcomes Study Short Form-36 [SF-36], with norm based means [NBM] <47 indicating a clinically meaningful worsening QOL compared to the general population), and evaluated relationships between demographic and clinical variables and psychosocial distress (measured by the Hospital Anxiety and Depression Scale [HADS], with higher scores indicating more distress). Demographic and clinical factors were tested in univariate models. Factors with a p < 0.2 were evaluated in multivariate models to determine factors associated with anxiety or depression (HADS subscale scores >11). Results: Of the 725 women who completed a baseline survey, 40 had ABC. Median age of ABC diagnosis was 37 (range 23-40). Median time between diagnosis and survey completion was 143 days. Other than general health (NBM 56.8) and role limitations due to emotional problems (NBM 53.8), SF-36 subscale scores of young women with ABC were lower compared to the general population, especially, bodily pain (NBM 27.4), social functioning (NBM 33.5) and mental health (NBM 44.3) scores. Physical and mental component summary NBM scores were 44.3 and 45.8 respectively. 30% (12/40) were anxious and 10% (4/40) were depressed according to HADS. The 4 depressed women also met criteria for anxiety. Women who were more financially comfortable were less anxious (OR 0.07, p=0.04). Logistic regression identified no other factors associated with anxiety, and no factors were associated with depression. Conclusion: QOL is impaired in young women with recently diagnosed ABC, particularly from bodily pain and disruption to social functioning. Many young ABC patients are anxious, while few are depressed. This study will be expanded to include young women who progressed to ABC. Further research is warranted to evaluate interventions to improve QOL and psychosocial distress in this population.
Lack of patient-clinician concordance (LOC) across disease and treatment status in cancer.
Authors: Chandwani Kavita Dayal , Zhao Fengmin , Morrow Gary R. , De Shields Teresa , Minasian Lori M. , Manola Judith , Fisch Michael
Published: March 2020

e20520

Background: The number and severity of cancer patients’ concerns is associated with their distress. Discrepancies between patient (pt) and clinician reporting of cancer pts’ symptoms and concerns have been reported during treatment. However, information on LOC across the disease and treatment status is lacking. This study explored LOC between pts and clinicians about pts’ bother related to disease and treatment status in those who needed assistance with questionnaires (NA) or self-administered (SA). Methods: Cancer pts and their clinicians in the Symptom Outcomes and Practice Patterns study rated pts’ bother (scale:0=Not at all, 4=Extremely) due to difficulties related to cancer, its treatment, side effects (SE), and comorbidity (COMORB), recoded to LOC ( 0=no difference between pts and clinicians, 1=any difference). Comparison of LOC proportions was conducted based on the disease status (4 groups: no evidence of disease [NED], local/regional [LR], metastases [mets], and mets+ LR) and current treatment (yes/no) using Chi square test. Results: The majority of pts (N=3013) were Caucasian (86%) females (70%) and had ECOG PS= 0 (87%). Mean age was 61.2 years (SD=12.4). 86.7% did not need help with the questionnaires/SA. Eight subgroups defined by disease status and current treatment showed statistically significant differences in LOC proportions re: bother due to treatment, SE, and COMORB in both the SA (range: 52.8%-86.7%, 41.6%-80.0%, 52.3%-81.3%, respectively, p<.001) and NA groups (range: 40.7%-82.4%, 29.6%-70.6%, 48.1%-72.8%, respectively, p<.05). Differences in the proportions of pts with LOC re: bother due to cancer were statistically significant for SA group only (range: 55.6%-81.3%, p=.01). In both SA and NA groups, pts with mets or mets+ LR had higher proportion of LOC re: bother due to treatment, SE, and COMORB than pts with NED or LR (p<.05). Conclusions: This study provides evidence of LOC in patient-clinician reporting of cancer pts’ bother re: disease and treatment status. Greater proportion of pts with advanced disease showed LOC. Further study of LOC in reporting bother related to various aspects of cancer experience is needed to confirm these results and to understand how they relate to outcomes of care. Clinical trial information: NCT00303914.
Association between cancer-related fatigue and other symptoms in breast cancer patients.
Authors: Peoples Anita Roselyn , Heckler Charles E. , Roscoe Joseph A. , Kamen Charles Stewart , Peppone Luke Joseph , Mustian Karen Michelle , Janelsins Michelle Christine , Moore Dennis Frederic , Coles Charlotte , Hoelzer Karen L. , Williams Jacqueline P , Morrow Gary R.
Published: March 2020

e20526

Background: Cancer-related fatigue (CRF) is one of the most prevalent side effects of cancer treatment and has a detrimental effect on a patient’s normal functioning and quality of life. At present, the underlying pathophysiology of CRF is poorly understood, as it is complex phenomenon involving the interaction of many factors. The relative contributions of the disease itself, different cancer therapies, and comorbid conditions (e.g., sleep disorders, nausea) remain unclear. Therefore, it is important to understand the association between them in order to develop better strategies for the prevention and treatment of CRF. Methods: The purpose of these secondary analyses was to examine the association between post-treatment fatigue with disturbed sleep (on a 0–10 scale), delayed nausea (on a 1–7 scale), age, and baseline fatigue. Analyses were performed on 541 breast cancer patients (mean age 54, 100% female) who completed a four-day diary assessing nausea and sleep following initial chemotherapy. Fatigue as its worst during the prior week (0 = no fatigue to 10 = fatigue as bad as you can imagine) was assessed both prior to chemotherapy and on Day 4. To determine associations between variables, Pearson’s correlation analysis and linear regression were performed. Results: Post-treatment CRF was significantly associated with baseline fatigue (r = 0.40, p < 0.0001), disturbed sleep (r = 0.45, p < 0.0001), delayed nausea (r = 0.37, p < 0.0001), and age (r = -0.22, p < 0.0001). Linear regression showed that a one unit increase in baseline fatigue, disturbed sleep, and delayed nausea was associated with increase in post-treatment CRF by 0.29, 0.37, and 0.42, respectively, all p’s < 0.0001. In addition, every ten years of increased age was associated with a decrease in post-treatment CRF by 0.33 (p < 0.0013). Conclusions: Post-treatment fatigue was found to be significantly correlated with baseline fatigue, disturbed sleep, and delayed nausea while negatively correlated with age in patients with breast cancer. These results demonstrate the importance of further research to better understand the underlying psychological and biological mechanisms for CRF in order to develop effective treatments. Supported by NCI grant CA37420.
Development and validation of the functional assessment of cancer therapy: Antiangiogenesis (FACT-AntiA).
Authors: Yount Susan , Kaiser Karen , Beaumont Jennifer L , Webster Kimberly , Wagner Lynne I. , Schenk Tom L. , Kuzel Timothy , Cella David
Published: March 2020

e20527

Background: Anti-angiogenesis therapies represent a significant and promising advancement in cancer treatment. Side effects from angiogenesis inhibitors, although generally milder than chemotherapy side effects, have the potential to impact Health-related Quality of Life (HRQOL) and may lead to dose reduction or discontinuation. Currently, there are no patient-reported outcomes (PRO) measures that specifically assess HRQOL related to anti-angiogenesis therapy. This study describes the development and validation of a PRO questionnaire for anti-angiogenesis therapy, the FACT-AntiA. Methods: Scale development included identification of 59 anti-angiogenesis side effects from the literature and clinician and patient input. Patient and clinician ratings of the importance of these side effects led to the development of a 24-item scale. Cognitive interviews with 10 patients confirmed item wording and meaning. To assess psychometric properties of the scale, 132 kidney cancer patients completed the FACT-AntiA and other PRO measures including the Functional Assessment of Cancer Therapy-General (FACT-G), the FACT-Kidney Cancer Symptom Index-19 (FKSI-19), and PROMIS Global Health at 3 time points. Patient responses to the FACT-AntiA were analyzed for internal consistency, test-retest reliability, convergent and discriminant validity, and responsiveness to change in clinical status. Results: FACT-AntiA side-effect subscales scores and total score were found to have good internal consistency reliability (most Cronbach’s alpha > 0.70). Test-retest reliability was greater than 0.70 for most subscales and individual items. All single items (except nosebleeds), subscales, and the total score significantly differentiated between groups defined by level of side effect bother. Conclusions: The number of patients who reported a change in their side effect bother was small so evaluation of FACT-AntiA responsiveness to change requires further study. The FACT-AntiA was developed and validated as a tool to enhance treatment decision-making and side effect management for patients receiving anti-angiogenesis therapies and is a reliable and valid index for evaluation of therapy side effects.
Prediction of major surgical complications by comprehensive geriatric assessment in elderly patients with gynecologic cancers: A prospective cohort study.
Authors: Kim Jae Weon , Suh Dong-Hoon , Kim Mi-Kyung , Kim Hee-Seung , Chung Hyun Hoon , Park Noh Hyun , Song Yong Sang
Published: March 2020

e20530

Background: To evaluate the ability of a preoperative comprehensive geriatric assessment (CGA) to predict the risk of postoperative complications in elderly patients who underwent primary surgery for gynecologic cancers. Methods: Sixty consecutive patients (26 ovarian, 16 cervical, 7 endometrial, 5 uterine sarcoma, 4 vulvar, and 2 metastatic cancers) older than 70 years scheduled to take surgery electively for gynecologic cancer were preoperatively assessed by CGA. Every category of CGA was evaluated for in-hospital postoperative complications and mortality within 30 days of surgery. Major complication included any complication of 2 or higher grade according to Memorial Sloan-Kettering Surgical Complication Criteria 12/99. Results: Mean age was 73.6±3.5 years (range 70-85). Overall postoperative complication rate was 30.0% (18/60) including 9 (15.0%) major and 8 (13.3%) multiple complications. Mean hospital stay was 18.4±13.3 days (range 3-81), during which in-hospital mortality was 2 (3.3%). Univariate analysis revealed that dependent instrumental activity of daily living (IADL) was associated with any postoperative complication (p=0.023), especially for multiple complications (p=0.019). However, poor performance status (PS) was associated only with major and multiple complications (p=0.021 and p=0.014, respectively). Multiple regression analysis revealed that dependent IADL was the independent risk factor for any postoperative complication (relative risk [RR] 8.0, 95% confidence interval [CI] 1.1-59.8, p = 0.042). Notably, poor PS was significantly associated with postoperative mortality (p = 0.006), however, dependent IADL with a marginal significance (p = 0.059). Conclusions: IADL and PS were useful to predict postoperative complications and related mortality in elderly patients with gynecologic cancers. Postoperative complications and related mortality can be prevented by identifying the elderly patients with gynecologic cancers who showed dependent IADL and poor PS in CGA.
Body composition in head and neck cancer patients undergoing concurrent chemoradiation.
Authors: Zatarain Lauren Azure , Murphy Barbara A. , Dietrich Mary S. , Silver Heidi J. , Gilbert Jill , Ridner Sheila H , Cmelak Anthony
Published: March 2020

e20531

Background: We report results of a randomized pilot study assessing the impact of amifostine and a low weight tailored resistance exercise (LWTRE) on body composition in head and neck cancer (HNC) patients undergoing concurrent chemoradiation (CCR). Methods: Forty patients with stage III-IVB HNC scheduled for primary or adjuvant CCR were enrolled. Patients underwent primary randomization to CCR +/- amifostine and secondary randomization to nutrition counseling +/- LWTRE. IV amifostine was administered prior to radiation. Nutritional counseling and LWTRE began day 1 of CCR and continued through month 6 post-CCR. Weight was obtained at baseline, 1, 3 and 6-months post-CCR. Patients underwent lean mass measures by dual-energy X-ray absorptiometry (DEXA) at baseline, 1 and 3 months post-CCR. Results: Mean weight loss (WL) was 11.6 ± 6.3 kg (p < 0.001) from baseline to 6 months post-CCR. Mean lean mass loss (LML) was 3.5 ± 3.0 kg (p< 0.001) from baseline to 3 months post-CCR. The greatest change occurred from baseline to 1-month post-CCR: 10% and 7% decrease in weight and lean mass respectively. The LWTRE was feasible and safe (no adverse events). Neither amifostine nor LWTRE impacted weight or lean mass loss. Conclusions: Results failed to demonstrate decline in WL/LML with either intervention. Data confirmed WL/LML as profound acute treatment toxicity. It underscored the protracted course of WL/LML. LML has been shown to predict clinical outcomes such as reduced functionality leading to decreased quality of life. Long term follow-up of patients is needed to clearly understand the trajectory and sequellae of body composition changes in HNC patients post-CCR. Novel interventions must be designed and tested to prevent LML. Clinical trial information: NCT00503776. [Table: see text]
The ability of physical performance test and Karnofsky performance status to identify elderly cancer patients requiring a comprehensive geriatric assessment: A comparative study.
Authors: Nassani Najib Antoine , Ghanem Sassine , Kassouf Elie , El Osta Lana , El Karak Fadi , Ghosn Marwan
Published: March 2020

e20534

Background: The role of Physical Performance Test (PPT) as a screening tool for patients in geriatric oncology requiring a Comprehensive Geriatric Assessment (CGA) has not been studied so far. We undergo this study to assess PPT as a screening tool in comparison with Karnofsky Performance Status (KPS) and CGA. Methods: One hundred patients, aged ≥ 70 and diagnosed with cancer participated in our study. Inclusion criteria were knowledge of Arabic, French or English and absence of significant cognitive impairment. Exclusion criteria were: KPS<60% or severe medical condition. ROC curves were used to compare PPT and KPS in identifying ≥ 2 impairments on CGA. Results: Median age was 76 years (70 – 89). Most frequent malignancies were: Lung (19%), colo-rectum (16%), and breast (15%). Stage IV was present in half of patients. Patients were at increased risk of malnutrition (46%) and malnourished (15%), had moderate to severe pain uncontrolled by medication (41%), were at risk of falls (42%), were suffering from frequent sleeping problems (43%), had vision (56%) and hearing (36%) impairment, have had urinary incontinence within one year (21%). All had social support in case of emergency. Cardiovascular (67%), diabetes mellitus (30%) and pulmonary (26%) were the most frequent comorbidities. A remarkable prevalence of geriatric problems was noted with 69% having ≥ 2 impairments on CGA. A good correlation existed between KPS and PPT r = 0.68 (p<.0001). PPT (Se=65%, Sp=84%, PPV=90%, NPV=52%, cut-off ≤24) was equivalent to KPS (Se=65%, Sp=81%, PPV=88%, NPV=51%, cut-off ≤80%) in identifying ≥ 2 impairments on CGA. Conclusions: Patients aged ≥ 70, diagnosed with cancer and having a KPS ≤ 80% or a PPT ≤ 24 must be referred to specialists in geriatric oncology or to geriatricians for a thorough assessment.
Development and validation of the hand-foot reaction and quality of life (HF-QoL) questionnaire for oncology.
Authors: Anderson Roger T. , Keating Karen N. , Doll Helen A
Published: March 2020

e20537

Background: Skin toxicity (hand-foot syndrome and hand-foot skin reaction, HFS/R) related to antineoplastic therapy is a significant issue in oncology practice with potentially large impacts on health-related quality of life (HRQL). Methods: A brief, patient self-reported questionnaire, The Hand-Foot Quality of Life (HF-QoL), was developed to measure HFS/R symptoms associated with cancer therapeutic agents and their effect on daily activities. The validity and reliability of the HF-QoL was tested in a phase 2b trial of sorafenib in 223 patients with locally advanced or metastatic breast cancer. Other measures completed included a patient rating of condition severity, the FACT-B, and the clinician-rated NCI-CTCAE [version 3.0] grading for rash. Psychometric properties tested included factor loadings, internal consistency, construct and discriminant validity, and responsiveness. The minimal clinically important difference (MCID) was estimated. Results: The final HF-QoL instrument comprises a 20-item Symptom rating scale and an 18-item Daily Activities scale. Each scale demonstrated excellent measurement properties and strongly discriminated between NCI-CTCAE grade and patient-rated condition severity with moderate to large effect sizes (>0·50 standard deviation). The Daily Activities domain had excellent internal consistency (Cronbach’s alpha 0·96) and was correlated with FACT-B, FACT-G (both r=-0·53) and Symptom scores (r=0·82). Both HF-QoL scores increased notably and linearly with increasing patient-rated condition severity (p<0·001). The MCIDs were estimated as 4 units for Daily Activities and 6 units for Symptoms means. Conclusions: The HF-QoL is a valid and reliable measure of symptoms associated with HFS/R and its effects on daily activities in this population of patients with advanced breast cancer. The HF-QoL is thus suitable for assessing HRQL impairment associated with HFS/R with cancer chemotherapeutic agents.
CYP2D6 pharmacogenetic testing: Beliefs and psychological effects in breast cancer patients treated with adjuvant tamoxifen (T).
Authors: Magnani Katia , Pezzolo Elisa , Gusella Milena , Bononi Antonio , Falci Cristina , Da Corte Donatella , Cretella Elisabetta , Nicolardi Linda , Menon Daniela , Brunello Antonella , Rosti Giovanni , Raiti Concetta , Montin Lisa , Soraru' Mariella , Vastola Francesca , Koussis Haralabos , Bozzi Paola , Parolin Veronica , Greco Filippo , Pasini Felice ,   Italian TAM Group
Published: March 2020

e20541

Background: Pharmacogenetic tests (PGT) are intended to predict the efficacy and toxicity of a specific treatment. There is a common concern that they may be misunderstood by patients (pts), confused with predictive tests for hereditary disorders and induce psychological distress. Methods: As part of a study aimed at correlating individual T activation capability with disease recurrence, CYP2D6 genotyping was offered to 203 early breast cancer pts. On enrolment, they received complete verbal and written information by their oncologist about the test and its purpose. Six months later they were asked to answer 4 questions concerning the nature and the possible psychogenic stress aroused by PGT. Their level of anxiety was assessed by the Zung-Self-Rating anxiety scale. Results: Anxiety was absent in 39%, within the normal limits in 50% or mild in 9% of pts. Only two pts had a moderate score. Anxiety was not associate with age or time from cancer diagnosis. Although not significantly, its score was higher in pts with larger tumors and positive lymph nodes. All pts agreed on the usefulness of PGT to enable the prediction of differences in drug response and toxicity. Some of them believed that they could predict some disease risks: the misperception was higher among elderly pts (> 70y, 50%) while was infrequent in younger pts (<39y, 12%). There was no association with the anxiety score. PTG related worries, although not generating a clinically detectable anxiety, were reported by 0%, 10% and 16% of all pts <39, 40-69 and >70 years old, respectively. Conclusions: CYP2D6 genotyping to predict tamoxifen activation was welcomed, well understood and was not associated with anxiety in the majority of breast cancer pts on adjuvant treatment. It seems that, when properly informed by their physician, patients show a positive attitude towards PG testing and no psychological distress. Funded by Regione Veneto. Clinical trial information: 532.
Efficacy and safety of a two drug-combination regimen for cancer-related cachexia in the clinical practice.
Authors: Madeddu Clelia , Dessi Mariele , Orgiano Laura , Antoni Giorgia , Serpe Roberto , Omoto Itaru , Cau Maria Chiara , Macciò Antonio , Mantovani Giovanni
Published: March 2020

e20556

Background: To test the safety and efficacy of a combination treatment (including nutraceuticals, i.e. quercetin, alpha lipoic acid and curcumin) with carnitine + celecoxib for the treatment of cancer-related anorexia/cachexia syndrome (CACS) in the clinical practice. Primary endpoints: safety, increase of lean body mass (LBM) and improvement of quality of life. Secondary endpoints: increase of physical performance (tested by grip strength and 6-min walk test, 6MWT) and decrease of inflammation (assessed by serum levels of IL-6 and Glasgow prognostic score, GPS). Methods: Outpatients with advanced cancer at different sites with CACS (i.e. loss of body weight >5% of the pre-illness or ideal weight in the previous 3 months) were eligible to receive: L-carnitine 4 g/day + Celecoxib 300 mg/day. All patients received as basic treatment polyphenols 300 mg/day, lipoic acid 300 mg/day, carbocysteine 2.7 g/day, Vitamin E, A, C, all orally. Treatment duration was 4 months. Results: From June 2011 to April 2012, 75 patients with advanced cancer (all stage IV) at different sites were enrolled: 40 completed the treatment and were evaluable (mean age 65 ± 9.6, range 32-82 years). Results showed a significant increase of LBM (by dual-energy X-ray absorptiometry and by L3 computed tomography) from baseline as well as physical performance assessed by 6MWT. Quality of life (assessed by EORTC-QLQ-C30) as well as fatigue (assessed by MFSI-SF) also improved significantly. ECOG PS and GPS decreased significantly. The treatment was safe, no grade 3–4 toxicities occurred and no patient had to discontinue the treatment due to severe adverse events. Conclusions: The results of the present study confirm the efficacy and safety of the two-drug combination regimen previously shown in a randomized clinical trial (Madeddu et al, Clinical Nutrition 31:176-182,2012). Therefore, this simple, feasible, effective, safe, with favorable cost-benefit profile, two-drug approach could be suggested in the clinical practice as a treatment for CACS.
Intra-arterial infusion of irinotecan loaded microparticles (IAIRIM) for symptomatic and unresectable colorectal cancer (UCRC): Preliminary report.
Authors: Comelli Simone , Bini Roberto , Gallo Giacomo , Savio Daniele , Viora Tiziana , Vaudano Giacomo Paolo , Leli Renzo
Published: March 2020

e20562

Background: We evaluated feasibility, safety and efficacy of IAIRIM on a compassionate use basisto treat locally UCRC and investigated a volume reduction of the target lesion. Methods: We considered patients with UCRC not eligible for any conventional treatment presenting severe anemia from rectal bleeding, colon obstruction and severe pain. A multidisciplinary evaluation was performed by surgeon, radiologist and oncologist. Patients underwent abdominal quadriphasic CT scan, in order to obtain a preliminary arterial mapping of the tumour; colostomy was performed in all patients. Angiography of superior and inferior mesenteric arteries was obtained to define the lesion vascularization and perform IAIRIM. A month later a new CT scan evaluation was performed to evaluate the volume of the target on Aw Volume share 2 (slice thickness 5mm). We defined the results adopting MASS, RECIST and mChoi response criteria. QoL was reported adopting Edmonton scale and EORTC QLQ-C30. Results: Ten patients were enrolled, IAIRIM was successfully performed in all without major complications. Ten patients experienced a clinical improvement with disappearance of bleeding and reduction of pain in a week. Fever lasting 36 hours (24-48) and minimal discomfort procedure related in were observed in all . Reduced but persisting muchorrea and tenesm were reported in 4 patient. After four months all patients were alive without pain or bleeding. 8/10 patients experienced mass reduction ( -39%; range -96% / +7%) and 2/10 no evidence of progression. QoL: Edmonton scale (considering only pain, fatigue, well-being and depression items) was around 7 in 8/10 patients before treatment and 6 in 2/10 patients. After treatment 6/10 patients reported mean score 3; 3/10 reported 4, 1/10 reported 2. Using EORTC QLQ-C30, mean score decreased from 3 to 2. Conclusions: IAIRIM seems feasible, with low side effects in patients bearing UCRC considered out of usual approaches. A reduction of symptomatic treatments and an increase of QoL (Edmonton and EORT QLQ-C30 scale) has been recorded in all patients. Volume reduction of the tumour has been observed in nine patients. Further experiences are warranted.
Automatic inpatient palliative care consultation (PCC): Too little, too late to impact quality of life for advanced cancer patients?
Authors: Rocque Gabrielle Betty , Campbell Toby Christopher , Barnett Anne Elizabeth , Quale Renae M , Eickhoff Jens C. , Bailey Howard Harry , Burkard Mark E. , Cleary James F.
Published: March 2020

e20565

Background: Patients with advanced cancer who are hospitalized have high symptom burden and a short life expectancy, which may warrant PCC. Methods: Using sequential cohorts, we prospectively assessed implementation of automatic PCC for hospitalized cancer patients. The primary outcome was hospice utilization. Secondary outcomes included evaluation of changes in quality of life (FACIT-PAL), symptoms (ESAS), satisfaction (FAMCARE), and anxiety and depression (HADS). Surveys were administered at baseline, 2 weeks and 3 months post-hospitalization. Chart abstraction was utilized to assess demographics, resource use, and survival information. Results: Patients were evaluated consecutively (65 in the control group, 70 in the intervention). At admission, 91% reported uncontrolled symptoms: 52% pain; 15% dyspnea. 60% of intervention patients received PCC during their first admission. 54 patients completed surveys (29 control group, 25 PCC group), 64 patients declined or were unable to complete surveys, 16 patients were excluded due to language barriers, physician preference, or not receiving surveys. Using an intent-to-treat analysis, there was no difference between patients in the control and the intervention group in FACIT-PAL (119 ± 29 vs 123 ± 30, p = 0.68 ), ESAS (28 ± 14 vs 26 ± 15, p = 0.74) HADS (13 ± 6.6 vs. 12.± 4.7, p = 0.58), or FAMCARE (58 ± 9.1 vs 59 ± 8.6, p = 0.61). In both groups, patients had modest worsening of symptoms and quality of life over the course of the study. Survival and Health Services data analysis, including hospice referral, is proceeding. Conclusions: Automatic PPC had little impact on patient-reported symptoms and quality of life. Limitations included: small patient population; high rate of incomplete surveys, likely due to illness burden; penetration of the PCC was limited to 60% by patient or provider preference and consultant availability. Our primary outcome analysis (hospice utilization) is forthcoming, as are data on survival and Health Services outcomes.