bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of cognitive function and quality of life in breast cancer patients receiving adjuvant dose dense chemotherapy.
Authors: Dabrow Michael B. , Szarka Christine E. , Moore Joanne , Chernick Michael R
Published: March 2020

e19519

Background: Breast cancer therapy related neurocognitive dysfunction, such as memory impairment and “chemo-brain”, has been reported by many women during and after receiving adjuvant chemotherapy. Studies evaluating this effect have had mixed results regarding its validity. No study has evaluated a specific regimen and none have examined dose dense therapy. We have serially evaluated the cognitive and quality of life changes in patients receiving dose dense adjuvant adriamycin/cyclophosphamide followed by pactitaxel (DD AT-P) chemotherapy. Methods: Patients with early stage breast cancer (Stages I, II) who were treated at a single community hospital cancer center and were given dose dense AC-P adjuvant chemotherapy were asked to participate in this trial. 45 patients were enrolled and 43 were eligible for evaluation with the following instruments: FACT-F, FAS test, MMSE, MNA and BDI. Tests were administered at the start of chemotherapy, at the completion of chemotherapy, at 6 months and 12 months after completing chemotherapy. The tests were administered by oncology nurses. Scores were evaluated using repeated measures analysis of variance testing whether or not the change from baseline test scores had a trend over time. Results: 43 patients were evaluated. Age range was 34-72 years with a median age of 52. 34 patients completed 4 evaluations, 6 completed 3 evaluations, 3 completed 2 evaluations. The only measures demonstrating significant trends were the FAS test (p=0.022) and the Functional Well-Being (p=0.002) and Physical Well-Being (p<0.0001) portions of the FACT-F. The changes over time for these measures all indicated improved performance over baseline at the completion of the trial. The remainder of the tests showed no significant change over time. Conclusions: Dose dense adjuvant chemotherapy with AC-P for breast cancer does not result in decreased cognitive or quality of life measures over time. Patients can be reassured that this specific program of therapy will not lead to long term decreases in mental function and quality of life.
Clinical signs of dying in cancer patients: A prospective longitudinal observational study.
Authors: Hui David , dos Santos Renata , Kilgore Kelly L. , Buosi Silva Thiago , Chisholm Gary B. , Perez-Cruz Pedro Emilio , Souza Crovador Camila , de Almeida Leite Raphael , Del Fabbro Egidio , de Angelis Nascimento Maria Salete , Zhukovsky Donna S. , GonÃƒÂµaves de Freitas Seriaco Fabiola de Lourdes , Reddy Suresh K. , Machado Frascari Luciana , Yennurajalingam Sriram , Paiva Carlos Eduardo , Dev Rony , Hall Stacy , Fajardo Julieta , Bruera Eduardo
Published: March 2020

e19528

Background: The fundamental process of dying has not been well characterized. We determined the frequency, onset, accuracy and likelihood ratio (LR) for various clinical signs in dying cancer patients. Methods: We systematically documented 100 signs/symptoms on consecutive advanced cancer patients admitted to palliative care units at MD Anderson Cancer Center (MDA) in the United States and Barretos Cancer Hospital (BCH) in Brazil every 12 hours from admission to death/discharge in 2010/2011. We analyzed the serial data from death backwards using generalized estimating equations for decedents, and calculated the accuracy and LRs for all patients. Results: 203/357 (MDA 52, BCH 151) patients died, and had the following characteristics: average age 58 (range 18-88), female 49%, Caucasian 76%, median admission length 6(Q1-Q3 4-9) days. The average palliative performance scale decreased from 50% to 20% (P<0.001). The frequency of pulselessness of radial artery (PRA), decreased urine output, respiration with mandibular movement (RMM), inability to close eye lids (EL), death rattle, vocal cord grunting, Cheyne Stokes and nasolabial drooping increased as death approached (P<0.001 for all), with high LR+ for impending death (Table 1). Presence of PRA, RMM and EL had a high specificity (100%), positive predictive value (99.4%) and LR+ (13) for death in 3 days. Conclusions: We identified highly specific cardiovascular, respiratory and neuromuscular signs associated with imminent death. [Table: see text]
The estimation of life-time for the patients who acquired resistance to standard chemotherapies.
Authors: Taniyama Tomoko , Hashimoto Kenji , Hirakawa Akihiro , Katsumata Noriyuki , Kodaira Makoto , Yonemori Kan , Yunokawa Mayu , Shimizu Chikako , Tamura Kenji , Ando Masashi , Fujiwara Yasuhiro
Published: March 2020

e19535

Background: Prognostication is important for the advanced cancer patients to make the most for the rest of their life. We examined the accuracy of oncologists’ clinical predictions of survival (CPS) and the factors that oncologists referred to in cancer patients who acquired resistance to standard chemotherapies. We also examined how oncologists share the information about the survival with patients and their family. Methods: Fourteen oncologists treating major adult solid malignancies (breast, lung, gastrointestinal, pancreatic, gynecologic cancer and sarcoma) participated in this observational prospective cohort study between Oct 2010 and Oct 2011. The oncologists were asked to fill in the questionnaire about CPS when patients acquired resistance to standard chemotherapies. Results: The data of 52 patients were available for analysis. The median CPS was 92 days (Interquartile range [IQR], 61 - 168), and the median actual survival (AS) was 80 days (IQR, 35 to 148). The median difference between CPS and AS (|CPS-AS|) was 21 (IQR, -26 to 50) days. According to Pearson correlation between CPS and AS (r = 0.55, p < 0.001), log(CPS) and log(AS) (r = 0.69, p < 0.001) and spearman correlation between CPS and AS (r = 0.66, p < 0.001), it was statistically considered CPS corresponded to AS. The proportion of patients with |CPS-AS| were as follows; within a week, 6%; within 2 weeks, 14%; and within 4weeks, 42%. Concordance rate between CPS and AS was more accurate in gastric and ovarian cancer while it depended on the oncologists. Although, age, oral intake, the number of chemotherapy regimens and the prognostic factors that oncologists referred to were not related with |CPS-AS|. Eighteen patients (35 %) were informed about the prognosis and thirty-seven patients (71 %) were provided with information about palliative care unit. Thirty-three patients (64 %) received best supportive care alone and eighteen patients (35 %) received further chemotherapies. Conclusions: Oncologists’ predictions generally correlated with AS. As long as the prediction of survival is based on the prognostic factors that oncologists referred to, CPS can be correct to within as least 4 weeks.
Effect of dose escalation with single opioid, fentanyl matrix, for current cancer pain management: Multicenter, prospective, observational study.
Authors: Koh Sung Ae , Kim Min Kyoung , Lee Kyung Hee , Lee Kyu Taek , Park Seung Woo , Nam Seung-Hyun , Han Hye-Suk , Ryoo Hun-Mo
Published: March 2020

e19538

Background: It is clinical experience that end-of-dose failure was commonly observed and many cancer patients increase the frequency of opioid administration because of that. Another treatment option could be to increase the dose of the opioid administered. High-dose fentanyl matrix use is known to be effective in controlling pain in cancer patients. To measure effectiveness of increase in single dose of fentanyl matrix in patients whose pain was not controlled sufficiently with the analgesic use in real practice at the investigator’s discretion, we perform the study. Methods: A multi-center, open-label, prospective, observational study was conducted in 30 hospitals in Korea between August and December 2008. Results: 452 patients were enrolled. A total 404 patients completed the study. Mean pain intensity decresed from 5.27 on the second to 3.37 at the end of the trial. There was significant difference in pain intensity (p < 0.001) between first and last visit. The percentage of pain intensity difference was 30.1%. The prevalence of end-of-dose-failure (EOD) at visit 1 was 73% of the enrolled 452 patients. After the use of the fentanyl patch EOD decreased from 73% to 56%. Pain intensity of patients experiencing EOD was 5.64 at baseline compared to 4.27 in patients without EOD. On Visit 2, pain intensity in patienst with and without EOD was 4.02 and 2.54. Of enrolled 404 patients, mean of increasing dose of fentanyl matrix was 55.6mcg/day. Satisfaction rate of investigator’s global assessment was 66.0%, and that of the patients’ global assessment was 63%. The rate of pain improvement was 33.7% by Clinical Global Improvement- Improvement after the use of the fentanyl patch. The observed adverse events were mainly nausea, asthenia, constipation and diarrhea. Conclusions: This study demonstrated that increasing dose of fentanyl patch decreased pain intensity, and decreased the rate of patients experiencing EOD. Also satisfaction rate was increasing after use fentanyl patch. Thus, fentanyl patch may be effective in cancer patients whose pain was previously not controlled sufficiently or who experienced EOD, the side effects were as could be expected with an opioid.
Cancer cachexia syndrome (CS): A symptom complex associated with yet distinct from fatigue in ambulatory cancer patients.
Authors: Mertens Wilson C. , Emmons Gregory Scott , Katz Deborah , Barham Ruth , Cassells Lucinda Jane , Dahiya Saurabh , Howard Leslie M.
Published: March 2020

e19543

Background: Fatigue and CS (Lancet Oncol 2011;12:489) are common, multifactorial symptoms in ambulatory cancer patients. Clinical and laboratory correlates require further evaluation, although erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), nausea and weight loss have been associated with both CS and fatigue. A practical classification of cancer-associated fatigue is lacking. Methods: Patients with cancer—newly diagnosed, receiving treatment, as well as those undergoing post-treatment surveillance and recurrent/persistent disease—were consented and screened with a visual aid. Those reporting moderate fatigue were asked to participate in a study assessing the degree and impact of fatigue using the FACT-G and study-specific questionnaires, followed by focused laboratory testing. Results: 102 patients were accrued. Mean age 60.2 years (95%CI: 58.0, 62.5); 80% female; no evidence of disease 55.9%; disease present/initial presentation 18.6%, persistent/recurrent disease 25.5%; >5% weight loss 35%; CS 39%; anorexia-CS 18%; increased ESR 49% and CRP 32%; currently receiving chemotherapy 16%. Patients currently receiving chemotherapy had more fatigue (p=.011); none of CS, >5% weight loss, disease presence/recurrence, histologic diagnosis, gender, age, pain, appetite, nausea, depression, exercise, blood pressure (BP), hemoglobin level, ESR or CRP were statistically associated with fatigue. CS was associated with increased ESR and reduced BP and appetite (all p<.001), and increased nausea and CRP (both p<.05) as well as disease presence/recurrence (p=.003). FACT-G total and physical scale scores did not differ between CS and other fatigued patients. Conclusions: CS affects a substantial proportion of ambulatory cancer patients screened for moderate fatigue; however, CS patients did not exhibit increased fatigue or poorer FACT-G scores despite differences in weight, disease extent, weight loss, or laboratory markers of inflammation when compared to other sampled patients. CS patients may represent a distinct subset of cancer fatigue, or this symptom complex may be distinct from fatigue even though present in the same patient.
A qualitative study of the subjective experience of chemotherapy-induced nausea in cancer patients and survivors.
Authors: Olver Ian N. , Eliott Jaklin A. , Koczwara Bogda
Published: March 2020

e19553

Background: Despite improvements in anti-emetics and reduction of chemotherapy-induced vomiting, nausea remains problematic. We hypothesize that a set of symptoms is identified by patients as nausea and these vary. Methods: Two groups of cancer patients (N = 42) with current or past experience of chemotherapy-induced nausea consented to semi-structured interviews about nausea, which were transcribed and analyzed. At interview, survivors were a median of 3.5 years (range 4 weeks – 15 y) post-treatment, median age 50 (range 25 – 80); current patients were being treated in an out-patient clinic, median age 54 (range 39 – 72). Both groups comprised 12 females and 9 males. Results: Across both groups, the nature, number, location, duration and intensity of experiences described as nausea varied; no single symptom was common to all descriptions. Physical and psychological symptoms sometimes but not always included dry-retching, vomiting, loss of appetite, indigestion, change of taste, dizziness, bloating, reflux, inability to concentrate, fatigue and physical restlessness. Location of nausea varied from head/neck, sternum, mid and lower abdomen and the whole body. Onset ranged from immediate to day 5 post-chemotherapy. Duration was from 1.5 hours to 6 months with conditioned stimuli continuing to trigger nausea 11 years post-treatment in one case. Intensity varied between and within, patients and successive treatments. For most, distinguishing features of chemotherapy-induced (as opposed to other) nausea were a constant presence over time, fatigue and emotional associations with the cancer diagnosis; for many, nausea negatively impacted on social and work interactions. Triggers also varied, and included food (smells), negative emotions including anxiety, movement, smells (e.g. hand-cream, cleaning products), treatment related events, tooth-brushing and mentioning nausea. Prescribed anti-emetics were consistently noted as reducing the intensity of, but for many, not completely alleviating, nausea; distraction and relaxation were preferred management techniques. Conclusions: Control of nausea will require personalized management of a range of physical and psychological symptoms.
Antiemetic effectiveness of palonosetron and first-generation serotonin inhibitors for high emetic risk chemotherapy in the post-aprepitant era.
Authors: Yun Jina , Jeon Young Woo , Kim Han Jo , Kim Kyoung Ha , Kim Se Hyung , Kim Hyun Jung , Lee Sang Cheol , Bae Sang Byung , Lee Namsu , Lee Kyu Taek , Park Sung Kyu , Won Jong-Ho , Hong Dae Sik , Park Hee Sook
Published: March 2020

e19554

Background: Palonosetron(PAL) is a 5-HT3 antagonist with an approximately 100-fold higher binding affinity for the 5-HT3 receptor compared to the other serotonic antagonists(i.e., ondansetron, granisetron, and dolasetron). Several large phase III trials have demonstrated the superiority of palonosetron compared with other 5-HT3 antagonists in preventing emesis associated with both moderate and high emetic risk chemotherapy regimens. But, these studies carried out in the pre-aprepitant era. We assessed that PAL is still preferred over the other serotonin inhibitors for high emetic risk chemotherapy in the post-aprepitant era. Methods: A retrospective analysis was made of all patients who underwent serotonin inhibitor, aprepitant and dexamethaxone for high emetic risk chemotherapy between 2009 and 2011. Group A received PAL, aprepitant and dexamethaxone. Group B received first-generation serotonin inhibitors(ondansetron, granisetron or dolasetron), aprepitant and dexamethaxone. Results: Four hundred fourty patients were included in the analyses: 331 patients in the Group A and 109 patients in the Group B. No case of grade 3-4 nausea/vomiting was noted. There were no significant differences between Group A and Group B for both acute and delayed CINV. The proportion of patients with a emesis-free during the acute phase(0-24 h) was similar in both groups: 275 of 331 patients(83%) in the Group A vs 88 of 109 patients(81%) in the Group B. The proportion of patients with a emesis-free during the delayed phase(24-120h) was similar in both groups: 255 of 331(77%) vs 76 of 109 (70%). Conclusions: In aprepitant era, all of the serotonin inhibitors seems to be equally effective for high emetic risk chemotherapy.
Treatment of post-herpetic pain with scrambler therapy, a patient-specific neuro-cutaneous electrical stimulation device.
Authors: Smith Thomas J. , Marineo Giuseppe
Published: March 2020

e19564^

Background: Post herpetic neuropathy (PHN) is common in cancer and hematologic malignancy patients. It can be debilitating and difficulty to treat effectively. Scrambler therapy, a patient-specific neurocutaneous stimulation device, can be effective in treating chemotherapy induced neuropathy (JPSM 2010) and other neuropathic pain (JPSM 2012). Methods: We treated ten patients, 2 with cancer as their primary diagnosis, with refractory PHN Scrambler therapy at two institutions. Scrambler therapy was given as 30 minute sessions daily for 10 days. Pain was recorded before and after treatment. Results: The patient mean age was 54 ± SD 13 years, 6 men and 4 women, with a mean duration of PHN for 15.6 months (range 2.5 to 48 months) without satisfactory relief despite conventional drugs. The average pain score rapidly diminished from 7.64 ± 1.46 at baseline to 0.42 ± 0.89 at one month, a 95% reduction, with continued relief at 2 and 3 months. Patients achieved maximum pain relief with less than 5 treatments. Conclusions: Scrambler therapy appears to have a promising effect on PHN, with prompt and continued relief and no side effects. Further research is warranted. [Table: see text]
External validation of the simple prognostic score in a palliative care clinic at a comprehensive cancer center.
Authors: Vij Brinder , Stabler Stacy Marie , Thaler Howard T. , Glare Paul A.
Published: March 2020

e19566

Background: Accurate survival predictions are essential for the optimal delivery of palliative care (PC). Clinical predictions of survival are notoriously inaccurate. Tools for making objective survival estimates in ambulatory cancer patients, who have months or years to live, are lacking. The Simple Prognostic Score (SPS) separated Canadian palliative radiotherapy patients into three groups with 12, 6 and 3 months median survivals, respectively. The aim of this study was to test the SPS in an outpatient PC clinic at a U.S. comprehensive cancer center. Methods: Retrospective chart review of 300 consecutive patients referred to one PC clinic at Memorial Sloan-Kettering Cancer Center (MSKCC). Cancer type, metastatic sites and Karnofsky performance status (KPS) score were used to calculate SPS (1 point each for non-breast cancer; non-osseous metastases; KPS score <70%). Outcome was date of death, obtained from the MSKCC institutional data base. Survival analysis was performed. Discrimination (non-overlap between groups) and calibration (percentage difference between estimated and observed survival) were measures of accuracy. Results: 79% (236 of 300) patients had advanced disease. Of them, 90% had cancers other than breast; 76% had metastases in sites other than bone; 27% had a low KPS score. The SPS score was 2 or 3 in 80%. By 10/31/11, 85% had died (median survival 4.9 months). SPS categorized the sample into four prognostic subgroups (see Table), with median survivals of 15, 9, 5 and 2 months respectively (log rank test χ2=38.71, d.f .3, p<0.0001). SPS was not very accurate, with poor discrimination (extensive intergroup overlap) but reasonable calibration (6-15% for the different groups). Conclusions: The SPS is user-friendly and helpful at the group level, but inaccurate at the individual level. Additional variables may narrow the prediction intervals, but will make the tool more complex. [Table: see text]
Intra-and inter-patient variability of baseline pain intensity scores during breakthrough pain in cancer.
Authors: Burton Allen W, , Filbet Marilene , Tayi Ravi , Perelman Michael Sidney , Knight Alastair D.
Published: March 2020

e19578

Background: Breakthrough pain in cancer (BTPc) can be assessed using a patient-reported 11-pt pain intensity (PI) scale (0=no pain; 10=worst possible pain). Little information has been reported about variation of PI between episodes and between individuals. This analysis examined intra- and inter-patient variation in baseline PI scores among patients participating in BTPc clinical trials. Methods: This was a pooled analysis of data from 2 randomized, double-blind, crossover studies that treated BTPc with fentanyl pectin nasal spray (Lazanda®, PecFent®) compared with placebo or with morphine sulfate immediate release. Patients were adults with ECOG score ≤2 who experienced BTPc despite background pain that was adequately controlled with ≥60mg morphine (or equivalent). Each study included dose titration prior to the double-blind treatment phase of 10 episodes of BTPc. Inter- and intra-patient variability of baseline pain scores for each episode were analyzed by ANCOVA using a mixed-effect model. Influence of covariables including demographics and ECOG score at study entry was assessed. Results: A total of 152 patients had 1399 BTPc episodes assessed. Mean (SD) age was 54.2 (12.0) yr; 81 patients (53%) were men. The mean ± SD episode baseline PI score was 7.3 ± 1.76 (range 2-10). Inter-patient variability of baseline PI scores was 75.9% and between-study variability, 3.5%; intra-patient variability among the 152 patients was 20.6%. Fixed terms for demographics and ECOG score were not significant factors influencing baseline PI scores at or below the 5% level. Conclusions: This analysis demonstrates that BTPc episodes have large variations in baseline PI scores between patients and that these scores are not influenced by demographics or ECOG score (0-2). However, individual patients show comparatively low variability in baseline PI scores between BTPc episodes. This supports the use of a consistent maintenance dose of an analgesic agent once it has been titrated to an effective dose.
The effect on patients with pulmonary fibrosis (PF) and advanced non small cell lung cancer (NSCLC): A prospective, feasibility study of S-1 and carboplatin.
Authors: Kato Terufumi , Yamaguchi Ou , Yoshida Masahiro , Fukushima Hiroki , Ogata Ryo , Nakazawa Atsuhito , Oda Tsuneyuki , Okuda Ryo , Ikeda Satoshi , Takasa Akiyuki , Tsuchiya Noriko , Enomoto Takahiro , Baba Tomohisa , Kitamura Hideya , Shinohara Takeshi , Nishihira Ryuichi , Komatsu Shigeru , Hagiwara Eri , Ogura Takashi
Published: March 2020

e19583

Background: PF is commonly concomitant disorder with lung cancer. Because PF sometimes deteriorates and results unfavorable clinical course, patients with PF are excluded from most cancer clinical trials. S-1 is a novel active oral fluoropyrimidine anticancer agent consisting of tegafur, gimeracil and oteracil potassium. Although most anti-cancer agent have pulmonary toxicity, post marketing surveillance reported S-1 has lower pulmonary toxicity incidence. We have conducted feasibility study of S-1 and carboplatin combination for patients with advanced or ineligible for other treatment modality of NSCLC patients. Methods: Patients with histologically or cytologically confirmed NSCLC, clinically diagnosed pulmonary fibrosis, aged 80 years old or younger, performance status 0-2 and chemo naive were eligible for the study. Carboplatin (AUC 5) was administered on day 1 and S-1 (80mg/m2/day) on day 1 to 14 for four to six cycles. Endpoints were response rate, common safety profiles and effect to PF. Results: From March 2009 to December 2011, 21 pts (19 males/ 2 females, median age 67 years old, ranged 55 to 77, 10 adenocarcinoma, 10 squamous, 1 adenosquamous, stage IIA: 1, IIIA: 3, IIIB: 9, IV: 4, recurrence: 4) were enrolled. All patients had moderate or severe PF. Treatment delivery; 1 cycle: 3pts, 2: 3pts, 3: 3pts, 4: 10pts, 5; 1pts, 6: 1pts. Partial responses were observed in 7 patients (RR; 33%). The median progression free survival duration was 4.0 months and the median overall survival duration in 10.4 months. During the treatment, 2 patient experienced moderate deterioration of pulmonary fibrosis, 1 experienced infectious pneumonia, all three patients recovered from the event. There was no treatment related death. Besides pulmonary toxicity, most common adverse events were myelotoxicities. Conclusions: This is the first trial of S-1 and carboplatin combination for patients with PF and NSCLC. The study revealed S-1 and carboplatin combination was feasible and active even in patients with PF and NSCLC who are usually excluded from cancer clinical trials.
Temporal versus probabilistic approach to survival estimation: Physician’s accuracy over time.
Authors: Perez-Cruz Pedro Emilio , Hui David , dos Santos Renata , Kilgore Kelly L. , Buosi Silva Thiago , Chisholm Gary B. , de Almeida Leite Raphael , Souza Crovador Camila , Del Fabbro Egidio , de Angelis Nascimento Maria Salete , Zhukovsky Donna S. , GonÃƒÂµaves de Freitas Seriaco Fabiola de Lourdes , Reddy Suresh K. , Machado Frascari Luciana , Dalal Shalini , Paiva Carlos Eduardo , Dev Rony , Hall Stacy , Fajardo Julieta , Bruera Eduardo
Published: March 2020

e19584

Background: Physicians are inaccurate in estimating survival. Both Temporal and Probabilistic approaches have been used for prediction. Serial prognostication might improve accuracy. In this study we compare these two approaches and assess whether serial prognostication improves accuracy. Methods: Physicians prognosticated survival daily for cancer patients admitted to palliative care units in two hospitals until death/discharge, using two prognostic tools: Temporal (What is the approximate survival of this patient in days?) and Probabilistic (What is the probability that this patient will be alive in 24 hrs?, 0% to 100%) (Hui et al. Oncologist 2011). Temporal prognosis was accurate if it fell within ± 33% of the actual survival. Probabilistic prognosis was accurate if the clinician selected a survival probability ≥70% and the patient survived in ≤24 hours or the clinician endorsed a survival probability ≤30% and the patient died. We compared physicians’ accuracy with each method at specific time points using Mc Nemar’s test. We assessed accuracy for each method over time comparing the accuracy at each time point with day -14 using a test of proportions. Results: Baseline characteristics of 306 patients included mean age 58 (18-88), female 69%, Caucasian 76%. Physicians were significantly more accurate in prognosticating survival with the Probabilistic v/s Temporal approach (p<.001 at each time point). The accuracy of Temporal approach was stable over time (Table). The accuracy of Probabilistic approach decreased close to death (Table). Conclusions: Physicians were more accurate at estimating probability of survival at 24 hrs than at estimating days to death. The accuracy of the probabilistic approach decreases as patient approaches death. Serial prognostication does not improve accuracy of survival estimation. [Table: see text]
Effect of enobosarm on physical function in cancer patients with < or ≥ 5% weight loss in a phase IIb trial.
Authors: Dodson Shontelle , Johnston Mary Ann , Hancock Michael L. , Steiner Mitchell S.
Published: March 2020

e19585

Background: Although cachexia has been defined as >5% weight loss, limited data exists on the prevention and treatment of muscle wasting prior to a patient becoming cachectic. Cancer induced muscle wasting can begin early in the course of a patient’s malignancy resulting in decline in physical function and other detrimental clinical consequences including less tolerability to chemotherapy, worse outcomes, and shorter survival - underscoring the importance of diagnosing and treating this condition at an early stage. Methods: We conducted a randomized, double blind, placebo controlled, multi-center study to evaluate the effect of enobosarm on physical function and muscle wasting in cancer patients. Subjects (n=159) were randomized to oral enobosarm or placebo for 16 weeks. Subjects were males >45y and postmenopausal females, with ≥2% weight loss in the 6 months prior to randomization and diagnosed with NSCLC, colorectal cancer, non-Hodgkin’s lymphoma, chronic lymphocytic leukemia or breast cancer. We report on changes in physical function based on weight loss of < or ≥5%in the 6 months prior to randomization. Results: 103 subjects (MITT) had physical function assessed by stair climb at baseline and week 16 with 24% losing <5% weight in the previous 6 months. Distribution of weight loss was similar across genders, however subjects with <5% weight loss were more likely to be ECOG=0 (<5% loss: 46.2%; ≥5% loss: 35.8%). Subjects with ≥5% weight loss had worse physical function at baseline compared to those with <5% loss (p=0.048). A significant improvement in physical function was observed in subjects that received enobosarm regardless of baseline weight loss (<5% loss, p=0.041, ≥5% loss, p<0.001) while subjects that received placebo failed to improve. Conclusions: Enobosarm was generally well tolerated and showed a statistically significant improvement in physical function in cancer subjects regardless of baseline weight loss. These data provide evidence that enobosarm may play an important role in the management of cancer patients by not only treating, but also preventing further decline in physical function and muscle wasting before a patient becomes cachectic.
Comparison of pain and efficacy between large-bore and small-bore chest tube drainage for malignant pleural effusion in Songklanagarind Hospital: A randomized controlled trial.
Authors: Porntepkasemson Apirudee , Geater Sarayut Lucien
Published: March 2020

e19608

Background: Malignant pleural effusion is one of the most common presenting symptoms in lung cancer. There has been no large RCT comparing large-bore and small-bore chest tubes in terms of pain and efficacy of management. Methods: A randomized controlled trial was conducted in 2011. Patients with malignant pleural effusion were randomly allocated to receive either a large-bore or small-bore chest tube. The primary objective was to compare pain using the Numeric Rating Scale. Other objectives included the efficacy of the drainage and pleurodesis and any complications were recorded. Results: Each arm comprised 21 patients. Median age was 61.2 years. Thirty-eight patients (90.5%) had adenocarcinoma; 14(33.3%) had received systemic chemotherapy. Pain score did not differ significantly between the groups from the time of tube insertion to removal. However, pain rose from day 4 until day 9 in the small-bore group. The proportion of patients requiring a second chest tube was higher in the small-bore group (small-bore = 7, 33.3 %; large-bore = 1, 4.8%; p 0.052). Complications were higher in the small-bore group. Five patients were complicated by tube occlusion which occurred only in the small-bore group (23.8 %, p 0.048). Times from tube insertion to lung expansion, to pleurodesis and to chest tube removal did not differ significantly between groups. Pleurodesis was effective in 70-80 % in both groups at the 28-day follow-up. Conclusions: No differences between large-bore and small-bore chest tubes were seen in pain, efficacy of drainage or success of pleurodesis. However, small-bore chest tubes had a higher rate of occlusion and more frequently required additional tube insertion.
Clinical outcome of recombinant human soluble thrombomodulin (rTM) for patients with disseminated intravascular coagulation (DIC) complicating advanced solid cancer: Retrospective analysis.
Authors: Takahashi Shin , Ohuchi Kohta , Kato Shunsuke , Shimodaira Hideki , Kakudo Yuichi , Akiyama Shoko , Yoshida Kozue , Shiono Masatoshi , Okada Yoshinari , Sugiyama Shunsuke , Saito Naoko , Lee Jin , Oishi Takayuki , Takahashi Hidekazu , Yoshino Yuki , Ishioka Chikashi
Published: March 2020

e19611

Background: Disseminated intravascular coagulation (DIC) is a syndrome characterized by the activation of coagulation leading to systemic microvascular thrombosis. DIC is frequently observed in patients with hematologic malignancy and often in patients with advanced cancer. Recombinant human soluble thrombomodulin (rTM) has been introduced as a new type of anti-DIC agent for clinical use in patients with hematological cancer or infectious disease. However, the efficacy for advanced solid cancer has not been elucidated. Methods: All patients with DIC complicating advanced solid cancer who were treated by rTM in Tohoku university hospital from December 2009 to November 2011 were enrolled in this retrospective study. DIC was diagnosed and scored according to the diagnostic criteria established by the Japanese Ministry of Health and Welfare (JMHW DIC criteria). Change in DIC score and period of overall survival (OS) after treatment of rTM (380U/kg/day) were evaluated. The Kaplan-Meier method was used to calculate OS. Results: Twenty-two patients (32% female) were enrolled. The median age was 61.5 (r: 32-82). The primary organs were 7 stomach, 3 colorectal, 2 esophageal and 10 other cancers. DIC score (63.6%), FDP (54.5%), PT-INR (45.4%), FBG (36.4%) were kept or improved in these patients between day 1 and day 5 in rTM treatment. Median OS (mOS) was 30 days (r: 2–301). Subgroup analyses revealed that mOS was longer in patients who underwent chemotherapy following rTM treatment than in patients who did not (114 days vs. 10 days, p = 0.0083). Patients with better ECOG PS (<2 vs. >3; 114 days vs. 15 day, p = 0.018), smaller number of chemotherapy treated before DIC (<2 vs. >3; 69 days vs. 6 days, p = 0.0008) also showed better mOS. No critical complication was observed. Conclusions: This study showed that rTM was effective and safe for patients with DIC complicating advanced solid cancer. PS and number of chemotherapy regimens could be predictive factor of rTM. We considered that rTM yield the chance of chemotherapy to advanced cancer patients with DIC by preventing deterioration of DIC.
Acceptability of the NCI patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE) in women with metastatic breast cancer (MBC).
Authors: Nichols Christine , Mitchell Sandra A. , Lang Kathy , Federico Victoria , Castro Kathleen M. , Rogak Lauren J. , Lalla Deepa , Clauser Steven B. , Reeve Bryce B. , Denicoff Andrea , Chen Alice P. , Piekarz Richard , Atkinson Thomas Michael , Mayer Musa , Brammer Melissa G. , Sit Laura , O'Mara Ann M. , Minasian Lori M. , Basch Ethan M.
Published: March 2020

e19633

Background: NCI PRO-CTCAE is a new patient-reported outcome measure designed to enhance adverse event (AE) reporting in clinical trials by integrating the patient experience. The PRO-CTCAE item bank includes items representing the frequency (F), severity (S) and interference (I) with usual activities of 78 symptomatic AEs. The aim of this study was to examine the acceptability of a subset of PRO-CTCAE items to women receiving treatment for HER2+ MBC. Methods: 207 women on active treatment for HER2+ MBC (median 47 months since MBC diagnosis) were recruited from 6 U.S. breast cancer support groups and completed a web survey that included 18 PRO-CTCAE symptoms. Respondents were aged 45-64 years (71%), white (94%), college-educated (72%), with health-related quality of life rated good to excellent (61%) and median EQ5D utility score of 0.8. To explore PRO-CTCAE acceptability and data quality, we examined item level missingness, endorsement frequencies and binary and free-text responses about the comprehensibility of PRO-CTCAE items. Results: Item level missingness across all symptoms for each PRO-CTCAE dimension (F, S and I) ranged from 1.0% to 5.3%, with a median of 2.9%; interference associated with decreased appetite had the greatest missingness (5.3%). Excluding this outlier, maximum missingness was 3.9%. Endorsement frequencies of response choices for S of insomnia, constipation, fatigue, pain, anxiety/worry and sad/unhappy feelings support acceptable instrument sensitivity (all adjacent response points endorsed by >7% of respondents). Most respondents (92%) thought the items were easy to understand; a few were uncertain about how to rate symptoms such as anxiety, depression, insomnia and nausea if they were present but partially controlled with medication. Conclusions: These findings confirm and extend those of other studies demonstrating the acceptability of PRO-CTCAE. Evaluation in a more heterogeneous sample, particularly with respect to education and cancer site, is underway.
Impact of racial and marital status on health services utilization among veterans with terminal cancer.
Authors: Lu Zhiqiang Kevin , Qureshi Zaina P. , Cho Michael , Wang Trent P , Yan Houling , Bennett Charles L. , Chang Victor Tsu-Shih
Published: March 2020

e19639

Background: Little is known about the association of socio-demographic factors with health services utilization (HSU) for patients with terminal cancer receiving palliative care. The objectives of this study were to evaluate for race or marital status associated variations in HSU among Veterans with terminal cancer. Methods: In an IRB approved protocol, 103 advanced cancer patients receiving palliative care in the Section of Hematology Oncology at a VA Medical Center, but not hospice, were followed every 4-6 weeks from the start of palliative care to death from 2000-2002. This study sample consisted of a subset of 39 pts who received palliative care for at least 24 weeks. Their charts were retrospectively reviewed for measures of health system utilization (HSU), including total length of hospital days, number of admissions, number of clinic visits and emergency room (ER) visits. ANOVA and Chi-square tests were used to explore for potential disparities of HSU across race or marital status. Results: Overall, the subset consisted of 17 Caucasians, 21 African American (AA), and 1 “other” by race. Among them, 21 were married, 7 were divorced, 6 were widowed, 4 never married and 1 had unknown marital status. The majority of patients had prostate cancer (39.47%) or lung cancer (28.95%). Mean total number of inpatient days was 23.6 days (SD=23), mean number of admissions was 2.9(SD=2.5), mean number of clinic visits was 27 (SD=25), and ER visits was 1.3(SD=1.8) per patient. Mean total hospital days were the longer for AA (25) compared to Caucasian (17.7) (p<0.01); the one pt from “other” had a total of 94 hospital days. The average number of ER visits was 0.48 for Caucasian, 2.0 for AA and 0 for other (p<0.05). Total number of inpatient days was longest for those who were never married (33.8 days), less for those who were married (26.0), divorced (12.7) or widowed (9.3) (p>0.05). A similar trend was found for clinic visits (NS). Conclusions: The pilot study identified racial but not marital status-associated variations in HSU among terminally ill cancer patients. These findings have implications for cost of care and should be confirmed in larger studies in our Veterans including caregivers. Funded in part by Project Death in America
Use and perceptions of complementary and alternative medicine in a community cancer center.
Authors: Cusnir Mike , Pozo-Kaderman Christina , Sullivan Irene , Vinas Elaine
Published: March 2020

e19646

Background: Studies over the past 10 years in the general population showed use of complementary and alternative medicine (CAM) to no more than 42% with the largest study reporting only 28% use in adults. In the cancer population one of the largest studies showed that 83.3% had used at least one CAM approach. After excluding spiritual practices and psychotherapy, 95.8% of participants were aware of CAM and 68.7% of those had used CAM. However most of this information has been obtained in academic medical centers that would be biased since the use of CAM has also been reported to vary by location, education and socio-economic status. Methods: We evaluated with a questionnaire similar to the one use by Richardson et al, in 2000 looking for prevalence and predictors of CAM use in a south Florida community cancer center with a culturally diverse patient population, many of Hispanic descent, we also evaluated the opinion about participating in CAM clinical trials.150 consecutive patients coming to the cancer center were given a questionnaire of which 112 are evaluable at the time of this report. Results: Average age was 66 years, 50 % of the patients were males, 56% of the patients were actively on chemotherapy, 10% on hormonal manipulations and 33% were not actively on treatment. 52% had heard of the term CAM, 34 % had heard the term integrative medicine, 18% had use CAM for their cancer treatment. Only 27% of the patients had discussed the use or interest in use of CAM with one of the health care providers. 59% expressed interest in participating in CAM clinical trials. Regarding specific therapies that the patients had used to “treat cancer” 8% had used dietary interventions, 15% had used movement therapies (TaiChi, yoga, etc.), 12% use of mind-body practices, 25% had used herbal and vitamin supplements and 25 % had used spiritual practices. Conclusions: Our study population had slightly lower use of CAM than in academic centers however the type of practices used appears to be different with increased use of mind/body and movement techniques over spiritual practices which might be a cultural effect. We also found a strong interest and will to participate in clinical trials that should be a window of opportunity to test these therapies in community settings.
Identifying resistance biomarkers against five clinically approved tyrosine kinase inhibitors in 45 cell lines.
Authors: Pénzváltó Zsófia , Tegze Bálint , Szasz Attila Marcell , Schäfer Reinhold , Gyorffy Balazs
Published: March 2020

e21005

Background: Clinical studies show low overall response rates of 10-47% to targeted cancer therapeutics. Our aim was to identify new biomarkers for predicting sensitivity against five already approved tyrosine kinase inhibitors. Methods: Sensitivity to sunitinib, erlotinib, lapatinib, sorafenib and gefitinib were tested in 45 cancer cell lines, and a resistance index was calculated for each cell line. The gene expression profiles (data were obtained by interrogating the raw microarray data of the caArray database) in the subset of resistant vs. sensitive cell lines were compared for each drug. Feature selection was carried out using significance analysis of microarrays and rank products. The results were validated by qPCR in the cell lines and - in case of four sunitinib resistance associated genes - in clinical samples by immunohistochemistry. Results: A set of 63 genes was identified as associated with resistance against the examined drugs. Overall classification accuracy of the prediction was 92.8% in a leave-one-out cross validation using prediction analysis of microarrays. The expression of the genes was validated by qPCR in the cell lines. The results confirmed 45/63 of the microarray-based resistance associated genes and 7/32 of literature based genes. All together 48 sunitinib-treated metastatic renal cell carcinomas were collected. The immunohistochemical analysis in these confirmed the correlation of the expression of RAB17, LGALS8, and EPCAM with overall survival. Conclusions: We identified new predictive biomarker candidates for five tyrosine kinase inhibitors, and validated a set of sunitinib resistance associated genes in an independent patient cohort.
Correlation of increased tumor expression of estrogen receptor alpha mRNA and low aromatase protein ratio with prognosis in resected non-small cell lung cancer (NSCLC).
Authors: Aresti Unai , Carrera Sergio , Rubio Itziar , Sancho Aintzane , Marrodan Ines , Muñoz Alberto , Martinez Mireia , Calvo Begoña , Buque Aitziber , Azkona Eider , Ruiz de Lobera Abigail , Lopez-Vivanco Guillermo
Published: March 2020

e21009

Background: Although several studies have shown the presence of estrogen receptors (ERs) in lung tumors, published reports show inconsistent conclusions. Biological role of ER-α, ER-β and aromatase in the development of NSCLC is unclear. Aim of this study was to investigate the prognostic value of ERs and aromatase mRNA-protein concentration in resected NSCLC. Methods: Lung tumor and normal lung were analyzed for expression of ER-α, ER-β and aromatase using a 7900HT Applied Biosystem Fast PCR System. Reverse transcription-polymerase chain reaction (RT-PCR) analysis was performed for the detection of ER and aromatase expression using RNA from lung cancer tissues immediately submerged in RNA Later (Qiagen) after surgery. Aromatase protein was detected with an enzyme-linked immunosorbent assay kit for human aromatase (USCN Life Science). Results: We included 96 patients (80 male/16 female) with resected NSCLC; 51% adenocarcinoma, 43% squamous, 6% others. Pathological stages: 43% I, 33% II, 22% III and 2% IV. Mean expression of ER-α in normal lung was significantly higher than in lung tumor (0.1554 vs. 0.1182, p < 0.0001). Tumoral expression of ER-β inversely correlated with cigarette consumption in current smokers (p=0.046). Patients with the highest values of tumoral ER-α mRNA had better overall survival than those with the lowest values (< p50 =107 weeks >p50 = 139 weeks; p= 0.037). Aromatase protein mean concentration in tumor lung was significantly higher than in normal lung (10.411 vs. 2.125, p<0.0001). Aromatase protein ratio, tumoral concentration/normal tissue concentration, was significantly linked to overall survival (p=0.024; Exp (B) =1.010; 95% CI Exp (B) = 1.001-1.020), showing that a lower aromatase protein ratio is associated with better overall survival. Conclusions: We report a significant association between quantitative expression of mRNA ER-α and overall survival in tumor of resected NSCLC. We define the relationship between tumoral/ normal tissue aromatase protein ratio and overall survival. A better understanding of estrogen action in lung cancer could provide the basis for future targeted therapies.
Analysis of BRAF mutations in circulating tumor cells selected by size from patients with melanoma and comparision to the primary tumor.
Authors: Wechsler Janine , Benali-Furet Naoual , Ye Fei , Avril Marie-Françoise , Boitier Francoise , Carlotti Agnes , Clauser Eric , North Marie- Odile , Paraiso Isbou , Cayre Yvon E
Published: March 2020

e21014

Background: The efficacy of anti-BRAF therapies in patients with melanoma has emphasized the need to identify BRAF mutations in the tumour. As circulating tumour cells (CTC) derive from the primary tumour (PT), their analysis may represent a non-invasive tool to follow the molecular-target in blood after tumour removal. Methods: This prospective study included 26 patients: 24 patients had confirmed melanoma, 2 patients had benign lesions (1 naevus and 1 pyogenic granuloma). Blood samples were taken at time of the PT surgical excision; 12 healthy donors were included as controls. The 24 patients, 13 females and 11 males, had invasive melanoma (13 superficial spreading melanoma, 7 nodular melanoma, 1 lentigo malignant melanoma, 1 desmoplastic melanoma, 2 unclassified melanoma.). The mean thickness was 7.8 mm. Cytology, immunophenotyping and analysis of BRAF mutations on exon 15 were performed comparatively in primary tumour and CTC from the same patient. CTC were selected by the ScreenCell method, a single-use innovative system to isolate rare tumour cells through a filter-membrane on the basis of their size. Nucleic acids DNA/RNA were extracted from live CTC after filtration. Results: Isolated CTC and microemboli were found in 21/24 patients and were found comparable to the primary melanoma cells. No CTC was found in 10 healthy donors and 2 patients with benign lesions. The mean number of CTC was 2 CTC per ml, the maximum was 4 CTC and 7 microemboli per ml. Malignancy of CTC was assessed on classic criteria: cell size larger than 15 microns, nucleo-cytoplasmic ratio > 0.5, presence of clusters composed of pleomorphic cells. CTC were positively immunostained either by S-100 or MART1/melanA or HMB45 antibodies; 4 patients were studied for BRAF mutations in both melanoma and CTC. The results (2 negative and 2 positive) were concordant in primary melanoma cells and CTC. The V600E-BRAF mutation was found in the 2 positive cases. Conclusions: The ScreenCell method of CTC selection by size allows to detect BRAF mutations in CTC of patients with melanoma. This simple method could be proposed to follow the molecular-target during the course of evolution and treatment after tumour removal.