bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic state of perifocal zone and resection line of skin melanoma.
Authors: Frantziyantz Elena , Dzhabarov Farkhad , Rosenko Liudmila , Pozdnyakova Victoria , Komarova Ekaterina
Published: March 2020

e19049

Background: The state of metabolism in perifocal zone and morphologically intact skin along resection line is of importance for the processes of neoplasm metastasizing and relapse, including skin melanoma. Normalization of the state of free-radical processes, first of all along resection line, and then in neoplasm perifocal zone, should be a characteristic of pathogenically substantiated neoadjuvant influence. Methods: to study activity of free-radical processes in tissue of skin melanoma relapse, its perifocal zone (PZ) (1 cm from tumour edge) and in skin along resection line (3-5 cm from tumour edge) we investigated concentration of vitamins E and A, activity of superoxide dismutase (SOD), catalase, summary peroxidase activity (SPA), and malonic dialdehyde level (MDA) in patients with skin melanoma (pT2-3N1-2M0). The study group included 54 samples after treatment (chemotherapy and radiation). Control groups: 45 samples before treatment (CG1) and 27 samples of intact skin after plastic operations (CG2). Results: After treatment MDA concentration in tumour tissue increased by 33.4% in comparison with the CG1, but remained 17.7% lower than in CG2. Average increase in concentration of vitamins E and A was equal to 1.8 times, catalase activity decreased by 30.3% in comparison with parameters before treatment (p<0.05). SOD/catalase coefficient was 1.3 times higher than in the CG1, but 3.4 times lower than CG2.More manifested changes in activity of free-radical processes were observed in PZ: MDA concentration level after treatment increased by 30% in comparison with the CG1, and differed from the one in CG2 only by 10% (p<0.05). Catalase activity decreased by 1.5 times and didn’t significantly differ from the corresponding parameter in tumour tissue after treatment. Normalization of concentration level of vitamins A and E without change of their ratio was observed. There was 1.6-fold increase of SOD/SPA coefficient in comparison with the CG1, however it was 2.4 times lower than CG2 (p<0.05). All parameters under study along resection line after treatment didn’t significantly differ from parameters in CG2. Conclusions: The performed treatment completely restores broken metabolism in skin along resection line, partially–in tumour perifocal zone.
Biosimilar medicines in oncology: Single-center experience with biosimilar G-CSF.
Authors: Salesi Nello , Di Cocco Barbara , Veltri Enzo
Published: March 2020

e19501

Background: A biosimilar medicine is one with proven similarity to a reference biological product for which the patent has expired and whose active ingredient is produced or derived from a living organism. Recombinant granulocyte colony-stimulating growth factors (G-CSF) are used for the prophylaxis of febrile neutropenia. Methods: In this observational study a total of 48 patients with solid tumours were treated with biosimilar Zarzio, a new biosimilar G-CSF for 4−14 days from the day following the end of chemotherapy. The primary prophylaxis group was composed of 10 patients with breast carcinoma receiving adjuvant chemotherapy (CEF: 5-fluorouracil 600 mg/m2, epirubicin 100 mg/m2 G1, cyclophosphamide 600 mg/m2 G1, q 21 for 4 cycles à docetaxel 100 mg/m2 G1, q 21); 17 patients with locally advanced or metastatic lung carcinoma (66% adenocarcinoma, 34% squamous) receiving 4–6 cycles of platinum-based chemotherapy; 6 patients with metastatic gastric adenocarcinoma treated with TCF (Taxotere 75 mg/m2, cisplatin 75 mg/m2, 5-fluorouracil 300 mg/m2 by continuous 24 hour infusion for 5 days, q 21) for 4–6 cycles; 4 patients with prostate adenocarcinoma treated with Docetaxel 75 mg/m2 G1, q 21 in 6 cycles. The secondary prophylaxis group was composed of 11 patients with colorectal adenocarcinoma (54.5% treated with adjuvant XELOX therapy: Xeloda 2000 mg/m2 G1à14, oxaliplatin 130 mg/m2 G1, q 21, and the remainder treated with first-line metastatic FOLFOXIRI therapy [CPT-11 165mg/m2 G1, 5-FU 3200 mg/m2 continuous infusion for 48 hours, oxaliplatin 85 mg/m2 G1, q 14]). Results: Three cases of febrile neutropenia were reported: two in patients with prostate adenocarcinoma and one case in a patient with pulmonary squamous cell carcinoma and multiple secondary skeletal lesions. These patients were treated with antibiotics with resolution of the clinical picture without hospitalization after 24 hours. Conclusions: Our experience indicates that the use of biosimilar G-CSF is safe and effective at reducing neutropenic complications in patients with mixed tumors and is associated with cost savings.
Therapy Management Patient Consensus (TheMaPaC): A patient perspective on published therapy management recommendations for TKI-treated patients with a special focus on sunitinib.
Authors: Eberhardt-Wetherington Berit , Gall Valerie , Lang Melanie , Schmidinger Manuela , Gruenwald Viktor , Claussen Christina , Wartenberg Markus , Kalanovic Daniel
Published: March 2020

e19502

Background: Therapy management is an essential component of patient care for RCC or GIST patients (pts) treated with TKI (e.g. Sunitinib). Preventive measures and early intervention can reduce or eliminate specific adverse events (AE) allowing for adequate therapy duration and improved quality of life. Published recommendations (RECs) for AE management often rely on theoretical aspects and limited evidence leading to heterogeneous or contradicting RECs. To overcome these issues, a collaborative approach of physicians, pts and Pfizer was established. Here we report on an extensive survey to deepen the knowledge on the validity and practicability of published RECs in 27 TKI treated pts (20 RCC; 7GIST). Methods: RECs (n = 221) for AE management in pts receiving sunitinib or other VEGFR-targeted TKIs were retrieved from the literature since 2006 (approval of sunitinib). RECs were transferred into a detailed questionnaire (QU) using patient-friendly language. Pts receiving sunitinib assigned one of 5 rating categories to each REC (positive experience (self/others); no information; negative experience (self/others). Results: 47 pts received the QU, 27 (15 female; median age 62 yrs) returned evaluable QUs. The pts have been on sunitinib therapy for a median of 16 months. On average, 49% of RECs received positive ratings; 44% based on individual experience. 20 RECs were rated positively by >80% of pts. The results indicate that patients had the most positive experience with RECs about patient/physician information on AEs, care/protection of feet, skin ointment use, food preference, hydration and fatigue reduction. Other REC ratings were heterogeneous, with a preference for measures that can be easily applied in daily life. It is notable that 47% of published RECs were unknown to the participants. Conclusions: To our knowledge, this is the first extensive patient survey on the validity and practicability of published RECs. The results identify a number of useful, established RECs from a real-life pts perspective. The results will be further evaluated and compared with an ongoing physician survey.
Meta-analysis of the effects on safety of front-loading (FL), every-2-week (Q2W), and Q3W dosing of darbepoetin alfa (DA) in patients (pts) with chemotherapy-induced anemia (CIA).
Authors: Glaspy John A. , Kotasek Dusan , Canon Jean-Luc , Tomita Dianne , Collins Helen , Schwartzberg Lee Steven
Published: March 2020

e19511

Background: Several studies evaluated if alternate dosing could decrease the time to hemoglobin (Hb) response. With recent safety concerns, this is now of limited interest; however, these studies may contribute to the understanding of safety risks. This study-level meta-analysis examined effects of FL, Q2W, and Q3W dosing of DA vs epoetin alfa (EA) and weekly DA dosing on safety in pts with CIA. Methods: Data from 11 studies (4 FL, 5 Q2W, 1 Q3W, 1 Q2W/Q3W) conducted between 1999 and 2006 in which the comparison group received 3-times-per-week (TIW) or once-weekly (QW) EA or QW DA were included in the meta-analysis. FL dosing differed between the studies and was defined as DA 4.5 mcg/kg or 300 mg QW for 4 or 5 weeks or until Hb > 12 g/dL followed by either DA 4.5 mcg/kg Q3W or a lower QW dose. Endpoints included deaths on study; disease progression (PD); embolic, thrombotic, and thromboembolic events; and rapid Hb rise (1 g/dL within 14 days). Random effects odds ratios (ORs) are provided comparing FL, Q2W, or Q3W arms to either TIW or QW active control arms. Heterogeneity was assessed using I2 statistic. Results: No differences in ORs for death, PD, embolic, thrombotic, and thromboembolic events or evidence of a more rapid rate of Hb rise were observed in FL, Q2W, and Q3W arms compared with controls (table). Conclusions: Results of this meta-analysis suggested that these adverse events were not related to FL, Q2W, or Q3W dosing of DA. [Table: see text]
Perceptions and barriers towards clinical trials participation in Asian cancer patients.
Authors: Soh I Peng Thomas , Tay Cheong Kiat Julian , Ho Gui Yi , Pang Angela , Voon Pei Jye , Ling Winnie Hui Yee , Tan Chee Seng , Lee Soo-Chin
Published: March 2020

e19523

Background: There is currently limited data on the perceptions and attitudes of Asian cancer patients towards therapeutic clinical trials (CTs). Understanding this is crucial to their successful execution. Methods: From May to December 2011, we surveyed cancer outpatients at the National University Cancer Institute, Singapore, and collected data on patient demographics, tumor information, awareness, perceptions, and willingness to participate in CTs. Results: 240 patients were surveyed, including 85 (35%) who had previously participated, 141 (59%) who had never participated, and 14 (6%) who had refused participation in a CT. The majority was Chinese (78.8%) or Malay (16.7%), 57.5% was female and median age was 56 years (range 22-83). There were no differences in demographics between patients who had, had not or refused participation in a CT. 135 patients (56%) had prior awareness of CTs, and were more likely to be female (p=0.027) or had metastatic disease (p=0.002). 111 (46%) patients were willing to participate in CTs given the opportunity, and were more likely to have prior awareness of CTs (76.6% vs 38.8%, p<0.001), to believe that CT sponsorship covers only the cost of trial drugs (52.3% vs 24%, p<0.001), and to state that paying for non-trial related or standard expenses was reasonable (35.1% vs 19.4%, p=0.006), compared to patients who were not willing to participate. Patient age, gender, education, income, or availability of health insurance did not influence willingness to participate. The majority of patients who had participated in CTs (66/85, 78%) reported only positive experiences, while 13 (15%) reported mixed experiences, and only 2 (2.4%) reported only negative experiences. The feeling of being treated as ‘guinea pigs’ (n=7), and fear of toxicities (n=5) were the main reasons cited for refusal to participate in CTs. Conclusions: Asian patients have moderate awareness of CTs, and slightly less than half the patients surveyed were willing to participate in CTs. Prior knowledge of CTs was associated with increased willingness to participate, and improving awareness through education could facilitate enrollment.
Palliative inpatient chemotherapy: Clinical benefit or harm?
Authors: Ali Maria , Cripps M. Christine , Balchin Katelyn , Spencer Jennifer , Wheatley-Price Paul
Published: March 2020

e19527

Background: Palliative chemotherapy (CT) is given with the goals of palliating cancer symptoms and prolonging life. Patients with a poor performance status (PS) generally derive less benefit from CT and may experience greater toxicity. Advanced cancer patients admitted to hospital generally have a poor PS, and yet palliative CT is often administered to hospitalized patients. The evidence to support palliative CT in hospitalized patients is scarce. We hypothesize that palliative in-patient CT does not result in meaningful clinical benefit. Methods: With ethics approval, a retrospective chart review was undertaken to report outcomes from in-patient CT at the Ottawa Hospital Cancer Centre between April 2008- January 2010. From hospital pharmacy records, all advanced solid tumor patients receiving in-patient palliative CT were identified. Patients receiving radical, curative, neo- or adjuvant therapy, or those admitted for an inpatient regimen, were excluded. The primary endpoints were overall survival following CT, place of discharge from hospital, and whether further CT was received. Results: We report 199 in-patients (23% breast cancer, 22% small cell lung cancer, 16% NSCLC, 39% other) who received CT (median 1 cycle, range 1-5) during the study period. The median age was 61 (range 19-88); 59% were female. The main reasons for hospital admission were dyspnea (31%) or pain (29%). At baseline 25% were anemic, 36% had leucocytosis and 70% were hypoalbuminemic (<30g/l). 67% were receiving 1st line CT. The median overall survival was 4.5 months (95% CI: 3.2 - 5.8). Longest survival was seen in SCLC patients (7.3m). 77% of patients were discharged home, but 17% died during the admission. 72% of patients received further systemic therapy. Factors significantly associated with shorter survival were hypoalbuminemia (HR 1.52, 95% CI 1.06- 2.18, p=0.02), and therapy in 2nd line or beyond (HR 2.10, [1.37-3.23], p<0.001). Receiving treatment beyond 1st line, and baseline leucocytosis, were both significantly associated with patients being less likely to be discharged home or receive further CT. Conclusions: While in-patient palliative CT is associated with short survival, many patients remain well enough to be discharged home and receive further therapy.
An evaluation of the drug interaction potential of netupitant with digoxin.
Authors: Baumann Sybille , Olivari Tilola Silvia , Spinelli Tulla , Timmer Wolfgang
Published: March 2020

e19530

Background: The new, highly selective neurokinin-1 receptor antagonist netupitant (NETU) has been developed to provide protection from nausea and vomiting in patients receiving emetogenic chemotherapy. There is evidence from in vitro studies that NETU is a substrate for and a weak inhibitor of the P-glycoprotein (Pgp). Pgp plays a major role in the pharmacokinetics of digoxin (DIG), a cardiac glycoside with a narrow therapeutic index. The possible interaction between NETU and Pgp has been assessed by analysing the effect of NETU on DIG pharmacokinetics. Safety parameters have also been assessed. Methods: This study was an open-label, fixed-sequence design to evaluate the effect of NETU on DIG at steady state in 16 healthy volunteers (8 male and 8 female). A loading dose of 3 x 0.5 mg DIG (0.5 mg every 6 hours) was given on day 1, followed by a daily oral dose of 0.25 mg DIG for 11 consecutive days (days 2-12); NETU was administered as single oral dose of 450mg on day 8. Serial blood and urine samples were collected for the determination of the pharmacokinetic parameters. Physical examination, vital signs, electrocardiogram (ECG), adverse events, clinical chemistry, hematology, urinalysis, and overall tolerability were reported. Results: Based on the AUC(0-24h) parameter at steady-state, the extent of DIG exposure was not influenced by NETU coadministration. The confidence interval of Cmin was within the 80-125% equivalence limits, while the observed Cmax was slightly over 125%, which was not considered clinically relevant. The excretion of DIG in urine was 57% after NETU coadministration compared to 55% of DIG alone. There were no gender-specific differences in the extent of absorption (AUC) for DIG, and no safety-related influence of DIG or NETU was observed on safety and laboratory assessments, vital signs, or ECG parameters. Based on historical data NETU pharmacokinetics was not affected by DIG coadministration. Conclusions: No clinically relevant interactions occurred between NETU and DIG. The results of this study suggest that the coadministration of NETU with Pgp substrates may not require dose adjustments. Study treatments were well tolerated.
Association of race and ethnicity with hospice use in pediatric oncology patients.
Authors: Thienprayoon Rachel , Leonard David , Lee Simon Craddock , Winick Naomi Joan
Published: March 2020

e19536

Background: Palliative care is aimed at preventing or relieving symptoms and suffering caused by a life-threatening condition. At the end of life, hospice is an important provider of palliative care. Adult minorities are underserved by hospice, but little is known regarding the prevalence of pediatric hospice use or the characteristics of its users. We sought to determine whether race and ethnicity were associated with hospice enrollment in pediatric cancer patients. Methods: We undertook a retrospective cohort study of oncology patients in our institution who died between January 1, 2006 and December 31, 2010. Inclusion criteria were patients treated for cancer or bone marrow transplant in which a hospice referral was appropriate. Exclusion criteria were age greater than 18 at diagnosis, death off treatment unrelated to cancer, transfer of care, death due to trauma or an acute process, if oncology or bone marrow transplant was not the primary service and if a patient was lost to follow up but recorded as deceased. The primary outcome variable was hospice enrollment, the primary predictor variable was race/ethnicity, and secondary predictor variables were patient diagnosis, religion and payer status. 202 patients were initially identified; 114 were eligible for the study, of which 95 were enrolled on hospice. The most common reason for ineligibility was death due to an acute process (n=46); other reasons included transfer of care (n=18), oncology not the primary service (n=9), patients lost to follow up and recorded as deceased (n=7) and death off treatment unrelated to cancer (n=2). Results: Multivariate logistic regression determined that race was significantly associated with hospice use (p=0.02), even after controlling for patient diagnosis (p=0.01) and payer status (p=0.04). In patients enrolled on hospice, race was not significantly associated with dying on hospice (p=0.10), even after controlling for diagnosis (p=0.08), payer status (p=0.15) and religion (p=0.57). Conclusions: These results indicate that cultural factors play a role in hospice enrollment in pediatric oncology. More studies are warranted to elucidate these factors, and to understand why families choose hospice for children dying of cancer.
Self-assessment system of febrile neutropenia (FN) by patients receiving ambulatory chemotherapy for solid tumor.
Authors: Kitao Akihito , Matsumoto Koji , Tanioka Maki , Negoro Shunichi
Published: March 2020

e19548

Background: Febrile neutropenia is one of the oncology emergencies, which usually should be timely assessed and treated at the hospital. In some areas of Japan, however, medical resources are limited in especially nights and holidays. In Hyogo Cancer Center department of medical oncology, majority of pts have breast and gynecologic (GYN) malignant disease, those who are relatively young and without COPD. These pts may be managed by a self -assessment system of FN, although the feasibility is still unknown. Methods: Self assessment system consists of three steps, such as, prescription of Ciprofloxacin 1200mg b.i.d., educating pts by the team (doctors, pharmacists, and nurses) with written material, and evaluation at the hospital if febrile episode (FE) continues for longer than 48 hours. FE is defined as body temperature higher than 38 °C. Frequency of FE, admission to the hospital, ICU stay, and 30 days mortality rate were assessed retrospectively. Results: From Aug. 2006 to Oct. 2011, 476 pts were treated in ambulatory chemotherapy center under self-assessment system. Median age was 58 years old (range; 17 - 82), 87 % of them were under 60 years old. Literacy rate was 100 %. All had solid tumors, 75 % of them had breast (n= 157) or GYN (ovary and primary peritoneal cancer; n = 155, cervix; n = 40, corpus; n = 4) malignancy. Platinum based regimens (n = 184) and anthracycline based regimens (n = 131) were dominant. FE occurred in 159 pts (33.4%). Forty three pts (9%) were admitted to the hospital. Two pts were admitted to ICU. 30 days mortality rate was 0 %. The median MASCC score of admitted pts was 21 (range; 14 - 21). About half (47 %) had high risk score (< 20). Conclusions: In areas with limited resources, self assessment of FN can be an alternative option, although that should be applied to young and literate pts educated by skilled medical team.
Effect of the patient's age on radiotherapy-based adverse effect.
Authors: Okur Yillar , Yucel Birsen , Atasever Akkas Ebru , Eren Mehmet Fuat , Babacan Nalan Akgul , Kacan Turgut , Kilickap Saadettin
Published: March 2020

e19575

Background: We aim to determine the acute side effects of radiotherapy and the contribution of age to side effect occurrence in patients treated with radiotherapy. Methods: The data of 346 patients having treatment at Cumhuriyet University Radiation Oncology Department in 2010 and 2011 were analyzed. The patients were evaluated according to Radiation Therapy Oncology Group (RTOG) one a week after starting to radiotherapy. Results: There were 167 women (48%) and 179 men (52%). Two-hundred-forty-seven (71%) of the patients were under the age of 65, 99 (29) were above the age of 65. Eastern Cooperative Oncology Group (ECOG) performance situation was 0, 1 and 2 in 278 (80%), 51 (15%) and 19 (5%) patients. Stage 1, 2, 3 and without metastasis stage 4 were found in 30 (9%), 105 (30%), 172 (50%) and 39 (11%) patients. Radiotherapy was applied to 55 head and neck regions (16%), 31 brains (9%), 86 breasts (25%), 30 thoraxes (9%), 52 abdomens (15%) and 90 pelvises (26%). Fifty-four patients (55%) of above the age of 65 received radiotherapy, 45 patients (45%) received chemoradiotherapy. One-hundred-twenty-six patients (51%) of under the age of 65, received radiotherapy and 121 patients (49%) received chemoradiotherapy. For all the patients, the ratio of radiotherapy dependent side effects was 89% (307). The verage time for occurrence was two weeks. When the treatment was over, the number of patients who lost more than five kg was 42 (12%). ECOG difference was seen in 70 (18%) patients. Twelve of them (4%) showed recovery in ECOG performance, 50 (16%) patients showed disruption. Seventy-nine patients (23%) had a interruption in treatment because of the side effects. The occurrence of dermal side effects was higher in the group of patients below the age of 65 and the occurrence of genitourinary side effects was higher in patients above the age of 65. Thedifferences for both of the side effects were statistically significant. Other side effects and time showed no difference between the patients under 65 and patients above 65. Conclusions: The age does not affect the acute side effects of radiotherapy or chemoradiotherapy, so that both groups can tolerate radiotherapy and chemoradiotherapy.
Feasibility of computer-based self-administered cancer-specific geriatric assessment (SA-CSGA) in older pts with gastrointestinal malignancy (GIM).
Authors: McCleary Nadine Jackson , Wigler Devin , Berry Donna Lynn , Sato Kaori , Hurria Arti , Ng Kimmie , Abrams Thomas Adam , Chan Jennifer A. , Enzinger Peter C. , Fuchs Charles S. , Wolpin Brian M. , Schrag Deborah , Meyerhardt Jeffrey A.
Published: March 2020

e19586

Feasibility of computer-based self-administered cancer-specific geriatric assessment (SA-CSGA) in older pts w/ gastrointestinal malignancy (GIM) Background: The CSGA (Hurria, JCO 2011) is a brief geriatric assessment consisting of validated measures primarily self-administered using paper format. We developed & tested feasibility of a computer-based SA-CSGA in pts ≥70 yrs w/ GIM. Methods: From 12/2009 - 6/2011, pts ≥70 yrs receiving treatment (rx) for GIM at Dana-Farber Cancer Institute were consented to complete SA-CSGA at baseline (T1= new or change rx) & follow-up (T2 = w/in 4 wks of completing rx). Feasibility endpts are (1) proportion of eligible pts consenting; (2) proportion completing SA-CSGA at T1 & T2; (3) time to completion of SA-CSGA; (4) proportion of MDs reporting change in clinical decision-making due to SA-CSGA. Results: Of the 49 eligible pts, 38 consented (55% female, 89% White, 76% enrolling prior to new rx). Mean age was 77yrs (range 70-89), 38% completed college, 49% married, 27% live alone, and 78% retired. 50% were diagnosed w/ colorectal cancer (ca). Mean MD-rated Karnofsky Performance Status was 87.5 at T1(range 60-100), 83.5 at T2 (range 70-100). At T1, 92% used a touch screen computer; 97% completed the SA-CSGA (51% independently). At T2, all pts used a touch screen computer; 71% completed the SA-CSGA (41% independently). Reasons for not completing SA-CSGA were withdrawal of consent (n=1 at T1 & T2), transfer of care (n=3; T2) or death (n=7; T2). The dominant reason for needing assistance was lack of computer familiarity (n=17 T1, n=14 T2). Mean time to completion was 23min at T1 (range 15-58); 20min at T2 (range 13-35). Among the 8 MDs who consented to participate, SA-CSGA added information to clinical assessment for 75% at T1 (n=27) and 65% at T2 (n=17) but did not alter immediate clinical decision-making. Conclusions: The computer-assisted SA-CSGA feasibility endpt was met for older pts w/ GIM although approximately half required assistance. While the SA-CSGA added information to clinical assessment, results did not impact clinical decision-making. Reasons for this may include relatively high-functioning patients enrolled in this study.
Chemotherapy-induced changes in the physiologic reserve of elderly patients diagnosed with cancer.
Authors: Molina-Garrido MJ , Guillen-Ponce Carmen , Munoz-Sanchez MM , Olaverri Hernandez A. , Ortega Ruiperez Carolina , Santiago Crespo JA , Carrato Alfredo
Published: March 2020

e19590

Background: Frailty is a biological syndrome of the elderly that is characterized by the loss of the reserve in multiple organ systems. The aims of this study were a) to identify the presence of frailty in the elderly with cancer, by measuring their functional reserve baseline and after chemotherapy treatment, and b) to assess which of the functional reserve parameters checked suffered a change ≥30%, suggestive of frailty. Methods: Prospective cohort study of oncologic patients ≥70 years of age, evaluated in a Spanish Unit of Cancer in the Elderly (from January 2010 to December 2011). Most of patients (88.9%) had a basal status between 0-1 (measured by the ECOG index). We collected information about the individual's physiologic reserve (skeletal muscle mass [SMM], walking speed, peak-flow, grip strength, creatinine clearance [CC] and Pfeiffer test). Parameters of functional reserve were determined at baseline and 4 months after chemotherapy was started. It was used a pre-post design, and a control group of patients not treated with chemoterapy (group B). To identify significant differences between the results of parameters of physiologic reserve it was used a t-student t test for independent groups. It was calculated the change percentage in each of these variables. Results: We analyzed data from 66 patients in group A (treatment with chemotherapy) and 68 in group B (no chemotherapy). Age average: 78.68 years. Gastrointestinal tumors (37.3%) and breast and gynecologic tumors (32.1%), others (30.6%); 28.8% were metastatic tumors. After chemotherapy, there were no significant differences in walking speed (p =0.323), handgrip strength (p =0.162), peak-flow (p =0.954), cognitive status (p =0.078) or CC (p =0.425). However, there was an increase in SMM (0.618 kg, 95% CI: 0.020 to 1.215, p =0.043). Changes after treatment were as follow: SMM and peak-flow increased by 2%, grip strength decreased by 15% and CC was reduced by 0.05%. Conclusions: The elderly physiologic reserve is not modified as a result of chemotherapy treatment, except for SMM. This change could be related to tumor response achievement. None of the physiologic reserve parameters was useful in this setting, as a "marker of frailty".
Simultaneous care in Italy’s Veneto Region Health District 8: Integrated assistance to provide better outcomes in end-of-life care.
Authors: Girardi Fabio , Paiusco Paola , Manente Paolo , Bortolin Michela , Ruggeri Maria Grazia , Biancon Antonella , Vicario Giovanni , Scelzi Elvira , Sgarbossa Gigliola , De Rossi Costanza , Vultaggio Giuseppe , Mazzola Giuseppe
Published: March 2020

e19595

Background: The number of cancer patients requiring active treatment and palliation for symptoms relief is progressively increasing, due to the possibility to significantly prolong survival even in persons affected by metastatic disease. Italian Board of Health, within the National Oncological Plan 2010-2012, gave “simultaneous care” the recognition as the most qualified model to ensure the best result regarding life expectation, quality of life, adherence to therapies. Methods: In Italy’s veneto region health district 8 a unit dedicated to palliative care works in cooperation with oncology clinic, medical wards, general practitioner, social services; periodical meetings are scheduled to review all the requests; each patient is given a multidimensional evaluation, to assess the care needs. The Unit is able to provide a daily home-care, with total parenteral nutrition if needed, management of infusional devices, invasive procedures such as paracentesis, in order to minimize the number of intervening hospital admissions. We considered the percentage of patients who received a simultaneous care approach between 2008 and 2010, the number of patients who died at home or in a hospice, the average time-period of care, the number of elapsing hospital admissions. Results: In 2008 268 new patients received assistance by the Palliative Care Unit, 273 new patients in 2009 and 434 new patients in 2010; 82 (31,3%), 70 (25,6%) and 111 (25,6%) were affected by advanced cancer, respectively; in 2008 208 patients out of 262 (79,4%) died at home or in a hospice, in 2009 224 patients out of 273 (82,1%), in 2010 376 patients out of 434 (86,7%); in 2008 the average time-period of care was 93 days (calculated as the ratio between the total number of days of assistance to patients as a whole and the number of patients), 88 days in 2009; in 2008 the average number of intervening hospital admissions was 0,26 (calculated as the ratio between the number of admissions and the number of patients), 0,28 in 2009. Conclusions: Our data show that the earlier the patient affected by advanced cancer is evaluated by Palliative care Unit, the higher is the likelihood to develop an adequate home- or hospice-base care plan.
Retrospective analysis of treatment tolerability in elderly oncological patients receiving cytotoxic therapy in a community setting.
Authors: Ho Gwo Yaw , Lovat Katherine , Bradbear Joseph , Allen Christian , Mclaughlin Laurie , Sanmugarajah Jasotha
Published: March 2020

e19598

Background: Cancer is highly prevalent in those above the age of 65 years. Elderly oncological patients are under-represented in clinical trials and there is a lack of clinical data to guide treatment decisions in this group of patients. We evaluated the cytotoxic treatment tolerability in this group of patients in a community hospital. Methods: Cytotoxic chemotherapies and tyrosine kinase inhibitors administered in Gold Coast Hospital to patients above 65 years of age between March 2010 and March 2011 were included. Data including number of comorbidities, concurrent medicines, ECOG status and treatment drug dose adjustment were obtained. The outcomes of treatment including treatment completion, early termination and its reason, toxicities and hospital admissions during treatment were also collected. Results: A total of 206 patients were identified. Majority had an ECOG score of 0 to 1 (89%) and number of co-morbidities between 0 and 3 (96%). Eighty percent of patients had initial or subsequent treatment dose reduction. Despite this, 53% of patients (n=109) did not complete the planned treatment; 68% had disease progression but 31% was due to treatment intolerance. There was a high number of reported grade 3 and 4 toxicities (n=84) and hospitalisations during treatment (n=154). Conclusions: There is a high rate of dose reduction and noncompletion of cytotoxic treatments even in a relatively healthy elderly population. We propose further prospective study incorporating in-depth geriatric assessment to evaluate elderly patients suitability for cytotoxic treatments. [Table: see text]
Risk of skeletal-related events (SREs) following initial diagnosis of bony metastases in breast, lung, and prostate cancer.
Authors: Lamerato Lois , Glass Andrew , Wolff Greg G. , Richert-Boe Kathryn E. , Taneja Charu , Edelsberg John , Czapski Natalie , Chung Karen , Richhariya Akshara , Oster Gerry
Published: March 2020

e19630

Background: Bony metastases (mets) are a common source of morbidity in patients (pts) with cancer, cause spinal cord compression (SCC), pathological fracture (PF), and bone pain, and often require radiotherapy (RT) and/or surgery to bone (SB). Methods: Using the tumor registry and electronic data stores at a large U.S. Midwest healthcare system that serves approximately 800,000 persons, we retrospectively identified all pts aged ≥18 years with primary breast, lung, or prostate cancer diagnosed between 1995 and 2009. Registry and electronic medical records were then used to identify pts with diagnosis of bone mets at initial cancer diagnosis or at recurrence. Trained technicians reviewed medical records for occurrence of SCC, PF, RT and SB—outcomes that have been collectively referred to as SREs. Cumulative incidence of these events was calculated in the presence of competing risk of death. Results: We identified 378 pts with breast cancer and bone mets, 272 with lung cancer and bone mets, and 420 with prostate cancer and bone mets. SREs were present at initial diagnosis of bone mets in 23% of breast cancer pts, 24% of lung cancer pts, and 10% of prostate cancer pts (Table). At 12 months, cumulative incidence of SREs was 57.3% for breast cancer (SCC, 5.1%; PF, 37.9%; SCC and/or PF, 40.2%; SB, 5.9%; RT, 27.4%), 62.7% for lung cancer (SCC, 8.9%; PF, 37.8%; SCC and/or PF, 43.3%; SB, 3.5%; RT, 32.4%), and 38.4% for prostate cancer (SCC, 7.9%; PF, 21.3%; SCC and/or PF, 26.7%; SB, 4.0%; RT, 22.9%). Use of bisphosphonates was largely confined to pts with breast cancer. Conclusions: Though breast, lung, and prostate cancers differ considerably in presentation, clinical course, and treatment, SREs are a common and serious problem in all three cancers among patients with bone mets. [Table: see text]
The effect of continuous exposure to serotonin receptor antagonism on delayed emesis: An analysis of 1,535 patients in two randomized clinical trials with granisetron (G), APF530, and palonosetron (palo).
Authors: Raftopoulos Harry , Oboyle Erin , Gralla Richard J. , Rosenberg Martin , Barr John
Published: March 2020

e19635

Background: Serotonin-type 3 receptor antagonists (5HT3RA) are recommended by all evidence-based guideline groups. Controversies remain over the role of 5HT3RA in delayed emesis and in dosages. This analysis was conducted to examine if: 1) serotonin antagonism helps prevent delayed emesis, 2) length of continuous exposure to a 5HT3RA impacts efficacy, and 3) higher doses of a 5HT3RA influence results. Palo, a 5HT3RA with a long half life, was superior to older 5HT3RA agents in single agent trials and to G + dexamethasone (dex) in a combination trial in untreated patients (pts) (Saito et al, Lancet Oncol 2009 – Trial 1). APF530 is an extended release formulation of 2% G (500mg = 10 mg of G) in a biodegradable polymer, which with dex showed non-inferiority with palo + dex in a mix of untreated and treated pts (Grous et al, ASCO 2009 – Trial 2). Methods: We analyzed results of only untreated pts from Trial 2 so that the population was similar to those in Trial 1 (previously untreated, highly or moderately emetic chemo and received dex + single administration of a 5HT3RA). This allows comparison, over 2 trials, of G, APF530, palo at 0.25 mg and 0.75 mg. Results: See table. All three groups treated with the long acting 5HT3RA (palo at 0.25 mg or 0.75 mg) or the extended release 5HT3RA (APF530) had similar efficacy in complete control of acute, delayed, or overall 5-day emesis. Only the short acting G was associated with poorer results, in delayed and overall 5-day control. Conclusions: This analysis indicates that 1) continuous exposure to 5HT3RA as a long acting agent or as an extended release formulation provide better emetic control than the standard 5HT3RA granisetron, even with added dex, and 2) similar results were found with palo at 0.25 mg and 0.75 mg. These results indicate a role for serotonin antagonism in delayed emesis provided the patient receives continuous exposure of a 5HT3RA agent. [Table: see text]
Superior survival in children with rhabdomyosarcoma treated as per IRSG compared to as per SIOP regimen.
Authors: Aung LeLe , Tin Aung Soe , Quah Thuan Chong ,   Pediatric Oncology Group-Singapore
Published: March 2020

e20003

Background: Rhabdomyosarcoma (RMS) constitutes nearly 4% of all children diagnosed with cancer in ethnically diverse small island city of Singapore (pop. 5 million). Methods: We compared 56 children with RMS from April 1993 to December 2010 from KK Women’s and Children’s Hospital and National University Hospital, Singapore. They were treated as per Intergroup Rhabdomyosarcoma Study Group (IRSG) regimen (n=25), Société Internationale Pediatrique D’Oncologie (SIOP) regimen (n=20), and various other regimens (n=11). Results: Median age of diagnosis was 6.3 (0.1 - 17.3 years) with a median follow-up of 2.5 (0 - 15.6 years). According to IRSG classification, there were 19 (35.1%) with low risk (LR), 21 (38.8%) with intermediate risk (IR) and 14 (25.9%) with high risk (HR) disease. Fifteen (26.8%) were alveolar subtype, 23 (41.1%) were embryonal and sub-classification was not available in 18. The primary sites of tumor were: head and neck (n=22); genitourinary (n=19); extremity (n=10); and abdomen (n=5). At the time of analysis, 80.0% (n=45) were alive with no evidence of disease, 9 were dead of disease, and two were alive with disease. The 5-year EFS and OS for the cohort was 81.8% and 80.3% respectively. By disease risk group, 5-year EFS for LR was 93.3% [95% CI, 88.9 – 98.5], IR at 94.4% [95% CI, 90 – 99.6] and HR at 42.9% [95% CI, 41.5 – 47.7] respectively (p<0.001). The 5-year EFS for risk group by chemotherapy received per SIOP vs. per IRSG revealed: LR- 100% vs. 90.0% (p=0.43); IR- 100% vs. 90.9% (p=0.40); HR- 0% vs. 57.1% (0.64) respectively. Of 16 (7= HR) relapses at median of 2 years, 4 of 4 treated as per SIOP regimen were dead of disease and 2 of 3 treated as per IRSG were alive at last follow-up. Conclusions: High risk disease treated as per IRSG regimen resulted in superior EFS and OS than per SIOP. Although relapsed disease can be salvaged after initial therapy using SIOP regimen, emotional and financial impact of disease relapse on the family is vast. It would be of interest to report whether our findings can be duplicated in a collaborative international study.
Identifying TRKA and TRKB specific pathways in neuroblastoma through phosphoproteomic analysis.
Authors: Volchenboum Samuel Louis , Kristjansdottir Kolbrun , Bergelson Ilana , Khan Saira , Brodeur Garrett M.
Published: March 2020

e20008

Background: Neuroblastoma is the most common solid tumor found in children and is difficult to treat given its genetic and clinical heterogeneity. The tyrosine kinase receptor, TrkB, is often co-expressed with the MYCN oncogene in high-risk tumors, whereas the TrkA receptor is most often found expressed in low-risk, non-MYCN amplified samples. There are differences in the gene expression profiles of TrkB- and TrkA-over-expressing cell lines, but they do not explain the phenotypic variation. We hypothesize that differences in protein translation and post-translational modifications have profound downstream effects on cellular signaling and disease phenotype. Methods: We performed quantitative proteomics using stable isotope labeling, phosphopeptide enrichment, and tandem mass spectrometry on parental SY5Y neuroblastoma cells and cell lines stably transfected with either TrkA or TrkB. Receptors were activated with NGF or BDNF and activation was inhibited with CEP-701 (Lestaurtinib), a selective tyrosine kinase inhibitor, currently in clinical trials. Samples were separated by gel electrophoresis, digested with trypsin, and applied to the mass spectrometer for protein identification. Results: We have performed quantitative phosphoproteomic analysis and compared protein expression levels and patterns in TrkA overexpressing, TrkB overexpressing, and parental SY5Y cells. The TrkA and TrkB receptors were activated with NGF and BDNF ligands, respectively, as evidenced by increased phosphorylation of ERK and AKT, with inhibition by CEP-701. Changes in protein abundance and pathway activation following both ligand binding and inhibition are being determined by quantitative phosphoproteomic analysis, and TrkA-specific and TrkB-specific differences will be presented. Conclusions: As current genomic techniques may underestimate the differences in protein expression, proteomic profiling holds great promise for describing how post-translational modifications such as phosphorylation can affect tumor phenotype. Our work may reveal key elements of TRK signaling pathways important in neuroblastoma tumorigenesis, and may lead to the identification of novel targets for therapy development.
Efficacy and tolerability of trabectedin in heavily pretreated soft tissue sarcomas (STS).
Authors: Alonso Teresa , Gajate Pablo , Casado Antonio , Segura Gonzalez Eduardo Raul , Ortega Luis , Cebrian Juan Luis , Talavera Pablo , Zugazagoitia Jon , Acosta Daniel , Diaz-Rubio Eduardo
Published: March 2020

e20513

Background: Advanced STS have a dismal prognosis with a median overall survival of 1 year, reported in most phase III clinical trials. Although newer targeted therapies are currently being evaluated, chemotherapy continues to be the mainstay of treatment. However, due to the limited activity of current treatments, new therapies are needed. Trabectedin, an alkylating agent to the minor groove of DNA, has demonstrated significant activity after failure of anthracyclines and ifosfamide. Methods: This is a retrospective analysis of 22 patients diagnosed with advanced, heavily pretreated STS, treated with trabectedin in a single institution. From 06/ 2000 to 06/ 2011, trabectedin was administered as a 3-hour infusion every 21 days at a dose of 1.1-1.5mg/m2 with steroid premedication. No patients were excluded from this analysis. Results: Median age was 53 years (range 21-82). The most frequent histologic subtypes were: 27% liposarcomas, 18% leiomyosarcomas, 13% malignant fibrous histiocytomas and 9% synovial sarcomas. One third of patients had received 3 or more prior therapy lines. Overall response rate was 8.33% and stable disease (more than 16 weeks) was achieved in 36.3% of patients (75% of liposarcomas and 50% of leiomiosarcomas). The median duration of response was 11 weeks (range 4-22). Dose reduction was required in two patients, but no patient discontinued treatment due to drug-related toxicity. There were no treatment-related deaths. The most relevant toxicity was grade 3/4 neutropenia in 25% of patients (one case of febrile neutropenia). Grade 3/4 transaminitis was observed in the only patient who received trabectedin with doxorubicin for one cycle, and continued with trabectedin monotherapy without further liver function test disturbances. A case of transient rhabdomyolysis was observed; the patient had mild renal dysfunction and liver metastases, but recovered completely. Grade 1/2 nausea, vomiting and asthenia were reported in 8.33%, 4.17% and 45.83% of patients, respectively. Conclusions: Trabectedin achieves significant clinical benefit in heavily pretreated advanced STS patients. Trabectedin was well tolerated with reversible and manageable toxicity, demonstrating an acceptable safety profile.
Urokinase-type plasminogen activator gene (PLAU) to predict clinical outcome in invasive lobular carcinoma.
Authors: Metzger Otto , Michiels Stefan , Singhal Sandeep K. , Bertucci François , Desmedt Christine , Fumagalli Debora , Salgado Roberto , Galant Christine , Veys Isabelle , Saini Kamal V.S. , Larsimont Denis , Winer Eric P. , Piccart-Gebhart Martine J. , Sotiriou Christos
Published: March 2020

e21010

Background: At the molecular level invasive lobular carcinoma (ILC) is mostly composed of luminal A (LA) (≈80%) followed by luminal B (≈15%) and a small fraction of HER2-positive (≈5%) tumors (Metzger et al SABCS2011). In ILC, Genomic Grade (GG) adds prognostic information to clinico-pathological (CP) characteristics (Metzger et al ASCO 2011). In this study we sought to evaluate the prognostic value of different gene signatures/modules in patients diagnosed with LA classic ILC. Methods: Gene expression data were generated from 184 consecutive frozen tumor samples using Affymetrix U133 Plus 2.0 arrays. ILC tumors were classified into molecular subtypes using the PAM50 classifier. ILC tumors characterized as classic ILC by pahtologists and as LA by PAM50 were selected for this analysis. Invasive disease free survival (IDFS) was defined as the interval between date of surgery and date of any invasive recurrence or death. Multivariate analyses for IDFS and overall survival (OS) adjusted for age, tumor size, nodal status and chemotherapy was performed for gene signatures/modules related to proliferation, invasion, immune response and signaling pathways (IGF1, PI3K, MAPK, Src, Wnt). Results: 125 LA classic ILC tumors were identified with a median follow-up of 6.6 years (95% CI 5.6-7.6). The addition of PLAU gene expression as continous variable to CP variables yielded a significant hazard ratio (HR) for IDFS (HR= 2.1 [1.1 – 4.1], Δx2= 4.5, likelihood ratio p = 0.03) and for OS (HR = 3.6 [1.4 – 9.6], Δx2= 6.9, likelihood ratio p = 0.009). GG as a continous variable yielded a significant HR for IDFS (HR= 2.6 [1.2 – 5.7], Δx2= 6.2, likelihood ratio p = 0.01), but not for OS (HR= 2.1 [0.8 – 5.5], Δx2= 2.5, likelihood ratio p = 0.11). In contrast, IGF1, PI3K, MAPK, Src, Wnt, immune response, gene-70 and gene-76 failed failed to add signficant independent prognostic value. Conclusions: In addition to GG, PLAU adds prognostic information to CP factors in LA classic ILC and may guide future drug development in this difficult to treat BC subset. Of interest, PLAU is involved in degradation of extracellular matrix contributing to cell migration and metastasis and is a major component of a validated breast cancer biomarker (UPA/PAI1).