bluuebunny/crossref_metadata_2025 huggingface dataset:
CD44 standard isoform expression is associated with diffuse large B cell lymphoma of non-germinal center B cell-like types
Authors: Kim W. , Oh Y. , Park C.
Published: March 2020

18531

Background: Diffuse large B cell lymphoma (DLBCL) can be subdivided into germinal center B cell-like (GCB) and non- germinal center B cell-like (Non-GC) types by immunohistochemical profiling. Previous studies showed better survival rate for the GCB groups. CD44 is necessary for tumor spread and metastasis and its expression is generally associated with unfavorable prognosis. We analyzed the expression and prognostic significance of standard isoform CD44s and its variant isoform CD44v6 in DLBCL types. Methods: Tissue microarray blocks were created from 52 nodal DLBCL with control tissue. Immunohistochemical staining for CD10, Bcl-6, MUM-1, CD44s, and CD44v6 were performed. The median follow-up period was 44 months. Results: Nodal DLBCLs were subclassified into GCB [CD10+ or CD10-/Bcl6+/MUM1+, n=17 (33%)] and non-GC subgroups [CD10-/Bcl6- or CD10-/Bcl6+/MUM1+, n=35 (67%)]. CD44s expression appeared more on non-GC cases of DLBCL (p=0.04). CD44s and CD44v6 did not result in any difference according to tumor stage, IPI scores, LDH levels. Upon survival analysis, CD44s and CD44v6 expression did not show any statistical correlation. Conclusions: CD44s expression may play a role during lymphomatogenesis of non-GC type DLBCL.

No significant financial relationships to disclose.
Clinical implication of distinction from clinical features and treatment outcome of malignant lymphoma in Korean childhood and young adult
Authors: Hwang I. , Yoo K. , Lee S. , Park S. , Park B. , Ko Y. , Kim K. , Park K. , Koo H. , Kim W.
Published: March 2020

18534

Background: The Clinicopathologic features of malignant lymphomas vary to geography and differ to age. The goal of this study was to find the implication of distinction from biology, clinical features and treatment outcome of malignant lymphoma in childhood and young adult. Methods: We analysed the clinical features including age, gender, histologic type, and treatment outcome of 294 children and young adults during 13-year period (from May 1993 to November 2005) in Samsung medical center and compared our study to all age group and western childhood and adolescence group on clinical features or treatment outcome in malignant lymphoma. Results: Median age at diagnosis was 20.7 years (range: 0.1–30.1 years). Male to female ratio was 1.37:1, Of 294 cases, there were 248 cases of non-hodgkin’s lymphoma (NHL) (84.3%) and 44 cases of hodgkin’s disease (HD) (15%). This rate was significantly different to rate of all age group (HD= 5.3%) (p=0.001). Of 248 cases of non-hodgkin’s lymphoma, 134 cases (54.0%) were B-lineage and 113 cases (45.6%) were T- or NK-cell lineage. Our study group had higher rates of T- or NK-cell NHL compared to all age group (p=0.001) and western group (p=0.001). Among 248 cases of NHL, the most common histologic type was diffuse large cell lymphoma (DLBL) in our study group. Burkitt’s lymphoma (BL) was the most common histologic types in Western study group. 5-year survival rate (5YSR) was 80.4% and was superior for BL and was inferior for NK/T cell lymphoma. However male T-LBL patients had better outcome in western study group. NHL and T-cell NHL had significantly worse outcomes than HD and B-cell NHL (p=0.049, 0.001, respectively). Comparing age-groups 0–10, 10–20 and 20–30, 5YSR was inferior for the oldest patients only in NHL-, T-cell NHL- and T-cell LBL-groups. Conclusions: Our study suggested environmental and genetic factor was associated with the development of malignant lymphoma.

No significant financial relationships to disclose.
Avascular necrosis of the jaw in multiple myeloma (MM) patients (pts) treated with bisphosphonates (BP)
Authors: Curreli L. , Palmas A. D. , Latte G. , Murgia A. , Gabbas A.
Published: March 2020

18538

Background: Oral cavity avascular bone necrosis (ABN) has been recently reported as an emerging serious complication in pts receiving BP for the treatment of hypercalcemia related to MM or metastatic solid tumors. Methods: We report the cases of 6 pts with MM treated initially with pamidronate and later with zoledronic acid (ZA). Results: Pts characteristics : M/F 3/3; mean age 58.4 (46–78); 4 IgG κ,1 γ and 1 κ MM; 5 St IIIA and 1 IIIB; mean history of disease 61.3 mo. (23–103); 5 pts had a relapsing MM refractory to several lines of therapy but 1 pt had received only high dose dexametazone (D); 2 pts had received autologous stem cell transplantation and 1 pt allogenic bone marrow transplantation; mean n.° of BP doses was 41.3 (17–81). At the time of ABN onset all pts were receiving ZA along with, respectively: D (2 pts); cyclophosphamide plus D (1 pt), bortezomib plus D (2 pts) and oral melphalan (1 pt). ABN was localized in 2 pts at alveolar bone of the right maxilla and presented as an inflammation of the gum, followed by a painful bone exposure. In the other 4 pts ABN was localized at mandible and presented as dental abscesses followed in 2/4 pts by cutaneous fistulization. Treatment has included in all pts discontinuation of ZA, antibiotics, chlorhexidine mouthwashes, pain control, minor regional débridement, and bone trimming. In 1 pt a more aggressive surgical approach was attempted at an other Institution and postoperative course was complicated by massive haemorrhage and complete loss of chewing. Four pts dead with progressive disease with a mean overall survival after ABN presentation of 6 mo.; 2 pts are alive after 3 and 4 mo. after ABN presentation; however in all pts ABN significantly worsened quality of life. Conclusions: Oral cavity ABN is a severe complication in refractory MM pts receiving BP. Mechanisms of action of BP that determine a reduction in osteoclastic activity and an accumulation of nonvital osteocytes with microfractures of old mineral matrix appear to play an important role. However other causes may be involved as a long history of disease; an uncontrolled progressive disease; type and doses of previous and present therapies, primarily steroids; status of oral cavity and teeth of pts and possibly the n.° of doses of BP.

No significant financial relationships to disclose.
Effect of combined treatment of bortezomib and valproic acid on multiple myeloma cells
Authors: Kim B. , Ahn K. , Kim I. , Park S. , Kim B. , Yoon S.
Published: March 2020

18539

Background: Valproic acid (VPA) has an activity of histone deacetylase inhibitor that is known to have in vitro cytotoxic effect on multiple myeloma (MM) cells. It was investigated that VPA could synergize with bortezomib for human MM cell lines. Methods: U266 cell lines were treated with bortezomib 50nM and/or VPA 0.6mM and then MTT assay, cell cycle analysis using FACS, immunoblot analysis, caspase-3 activity assay, and IL-6 ELISA assay were performed. Results: Bortezomib activated caspase-3 and induced G1 cell cycle arrest. In MTT assay, VPA suppressed the U266 cell proliferation with IC50 of 0.6mM and combined treatment of bortezomib and VPA had more inhibitory effect than bortezomib alone. This combination caused further G1 cell cycle arrest, caspase-3 activation, and lowered IL-6 secretion from U266 cells than bortezomib, respectively. In immunoblot analysis, this combination further decreased the expression of cyclin A, cyclin D1, cyclin E, CDK2, CDK4, and CDK6, whereas up-regulated p21 and p27 expression than bortezomib alone. Conclusions: The combined treatment of bortezomib and VPA has a more significant anti-myeloma effect than bortezomib alone.

No significant financial relationships to disclose.
The value of combined modality therapy in elderly patients with stage III non-small cell lung cancer (NSCLC)
Authors: Schild S. E. , Mandrekar S. J. , Jatoi A. , McGinnis W. L. , Stella P. J. , Deming R. L. , Jett J. R. , Garces Y. I. , Allen K. L. , Adjei A. A.
Published: March 2020

19503

Background: This study was performed to assess the value of combined modality therapy in elderly patients by comparing the differences in outcome of those who received radiotherapy (RT) alone or RT plus chemotherapy for stage III NSCLC. Methods: North Central Cancer Treatment Group (NCCTG) performed 2 recent phase III trials for stage III NSCLC. The first trial, 90–24–51, included 3 arms: once-daily radiotherapy (QDRT) alone, twice daily RT (BIDRT) alone, and concurrent chemotherapy plus BIDRT. The second trial, 94–24- 52 included 2 arms and compared concurrent chemotherapy with either QDRT or BIDRT. The chemotherapy arms of both trials included etoposide and cisplatin administered concurrently with RT. Only the patients ≥65 years of age (elderly) who participated in these trials were included in this analysis. Results: Of the 166 elderly patients included in this analysis, 37 received RT alone and 129 received concurrent chemotherapy plus RT. The median and 5-year survival rates were 10.5 months and 5.4% for the RT alone group compared to 13.7 months and 14.7% for the RT plus chemotherapy group (log-rank p=0.05). Patients who received RT plus chemotherapy experienced significantly greater severe (grade ≥3) toxicity than those who received RT alone (89.9% versus 32.4%, p < 0.01). Conclusions: Elderly patients who participated in these trials appear to gain a survival advantage from RT and chemotherapy compared to RT alone. As is the case with younger patients, this benefit comes at the cost of additional toxicity.

No significant financial relationships to disclose.
A novel xenograft model to test the ovarian toxicity of chemotherapy agents in women
Authors: Oktay K. H. , Oktem O.
Published: March 2020

19504

Background: Many chemotherapeutic agents, especially of alkylating family, alter fertility in premenopausal females (1). While the impact of well-established agents such as cyclophosphamide (Cy) on fertility is well known (2), data are not available for newer agents. Moreover it is not practically possible to determine the individual ovarian-toxicity of each drug and the cellular mechanism of this damage from clinical trials.Thus our specific aim was to develop a xenograft model to characterize the impact of chemotherapy agents on human ovary. Methods: Ovarian pieces of 2x2 mm from 24 wk old abortuses were xenografted subcutaneously to immunodeficient mice (SCID) (n=52). At this gestational age ovarian histology is simiar to young females. Half of the animals received a single dose of 200 mg/kg of Cy intraperitoneally 14 days after the xenografting, while the other half received saline. Grafts were recovered from the control and treated mice 12, 24, 48, and 72h after the Cy injection (n=6–7 per time point), and serially sectioned for primordial follicle counts. Apoptosis was assessed with TUNEL assay. PECAM-1 staining, as well as intra-vital fluorescein conjugated lectin and Evans blue labeling were performed to assess microvasculature by confocal microscopy. All experiments were performed in triplicate. Results: While there was only 12 % loss 12h following the treatment compared to controls (p>0.05), the follicle loss significantly increased at 24h (53%, p<0.01) and peaked at 48h (93 %, p<0.0001), and reduced at 72h (70 %, p<0.001). TUNEL staining peaked at 12h, earlier than the follicle loss; then decreased at 24h and 48h, and faded at 72h. Less than 1% of follicles were TUNEL positive in controls. Xenograft vasculature was similar to non-xenografted tissue indicating that the ex vivo tissue drug delivery was similar to the in vivo delivery. Conclusions: A single injection of a typical dose of Cy can result in the loss of up to 93 % of ovarian reserve in a human ovarian xenograft model, consistent with the data from clinical trials. Fetal ovarian xenografting is a promising model to characterize the gonadotoxic effects of current and emerging cancer drugs without a need for lengthy clinical studies. 1. J Clin Oncol. 2006;24:2917–31 2. Hum Reprod Update. 2004;10:251–66.

No significant financial relationships to disclose.
Comparison of bedside estimates of renal function and measured glomerular filtration rate (GFR) in 510 adult oncology patients
Authors: Dooley M. J. , Poole S. G. , Rischin D.
Published: March 2020

19512

Background: Various bedside formulae have been used in practice to estimate renal function to predict drug dosing. Recently the ‘4-variable Modification of Diet in Renal Disease’ (4-v MDRD) equation1 was derived in patients with chronic renal disease and has been advocated for application in oncology. The aim of this study was to compare measured GFR with estimates from formula based equations in adult oncology patients. Methods: GFR was determined using technetium-99m diethyl triamine penta-acetic acid (Tc99mDTPA) clearance, serum creatinine (Jaffe method) was measured and renal function estimates calculated using 4-v MDRD, Cockcroft and Gault (CGF), Wright, Martin, and Jelliffe (JF) formulae. Accuracy, bias (mean % error (MPE)) and precision were assessed for varying levels of GFR, body mass index (BMI), age and gender. Results: In 510 adult oncology patients (323 male, 187 female, mean age 63years, range 17–87years) GFR was determined using Tc99mDTPA clearance (mean 84mL/min, range 16–205mL/min). The mean (range) calculated GFR was 72mL/min/1.73m2(9–162mL/min/1.73m2), 71ml/min (11–267mL/min), 78mL/min (12- 195mL/min), 81mL/min (12–279mL/min), 64mL/min/1.73m2 (10–165mL/min/1.73m2) for 4-v MDRD, CGF, Wright, Martin, and JF formula respectively. Bias, precision and accuracy (%within 30% and 50% of true GFR) of estimates are shown in the table . The Wright and Martin formulae had greater bias relating to degree of renal function and gender respectively. The 4-v MDRD equation provided a less biased estimate compared to the CGF across all levels of renal function and BMI. Conclusions: When compared to measured GFR, the 4-v MDRD equation provides a less biased estimate compared to the other formulae evaluated across a range of variables including degree of renal function and BMI. The limitations of all the bedside estimates must be understood to allow appropriate clinical utility. 1. Levey AS, et al. Ann Intern Med 2006; 145: 247–254.

[Table: see text]

No significant financial relationships to disclose.
How much can patients, with low Karnofsky performance status and advanced non-small cell lung cancer, benefit from cisplatin-based chemotherapy? A retrospective analysis of a phase III randomised trial
Authors: Paesmans M. , Lafitte J. , Berghmans T. , Lecomte J. , Alexopoulos C. , Van Cutsem O. , Giner V. , Efremidis A. , Berchier M. , Sculier J.
Published: March 2020

19516

Background: Performance status (PS) is a strong independent prognostic factor for survival in patients with advanced non- small cell lung cancer and administration of platinum-based chemotherapy (CT) in patients with poor PS is associated to more severe toxicity. Our purpose was to determine whether poor PS patients (ie those registered with a performance index of 60–70 on the Karnofsky scale) could benefit from CT in terms of clinical improvement defined as reaching, during CT, a PS of at least 80 on the same scale (ECOG PS 0 or 1). Methods: Retrospective analysis of a randomised trial performed in advanced NSCLC where 485 patients received three courses of GIP (gemcitabine + ifosfamide + cisplatin) induction CT, in order to determine the potential clinical benefit of conventional cisplatin-based CT in patients with poor PS defined as 60–70 on the Karnofsky scale. Results: 387 (80%) patients had good PS (Karnofsky 80–100) and 98 (20%) poor PS. Response rates were respectively 38 and 28% (p=0.06), no independent predictive value for PS was found using response to CT as endpoint. Clinical improvement was observed in 25% (95% CI : 15%-38%) of the poor PS patients (respectively 38%, 20% and 14% in case of response, no change and progression, p=0.05). Nine additional patients improved from 60 to 70 during induction CT. Improvement occurred earlier in responders (rates of patients with improvement were 12% after 1 course, 31% after 2 courses and 38% after 3 courses compared to 3%, 5% and 17% in the non responders). Survival of patients with poor PS was significantly worse but survival of responders was similar, whatever initial poor or good PS (logrank test after landmark, p=0.47, HR=1.18, 95%CI: 0.76–1.84 for poor responders). If non fatal toxicity was relatively similar as well as dose intensity delivered after 3 CT courses, there were more toxic deaths (including vascular and cardiac fatalities) in poor PS patients (2.1% versus 9.2%; p=0.002). Conclusions: Although toxicity is increased, combination chemotherapy is associated with clinical improvement in a non negligible rate of patients with poor PS in case of advanced NSCLC.

No significant financial relationships to disclose.
How different are epidemiology and treatment of cancer persistent pain (PP) and breakthrough pain (BTP) in elderly patients (pts)? Results of a French prospective survey
Authors: Di Palma M. , Duclos R. , Tessier C.
Published: March 2020

19520

Background: Efforts have been made in the recent years to improve pain care in cancer pts, especially for elderly ones Methods: We conducted a national survey in France in order to evaluate the actual situation. Data were collected from 100 cancer centers and analyzed using SAS software. Only adult pts treated for cancer pain, with their treatment initiated less than 8 days before study, were considered. Comparisons were made considering pts under and over 70 years old Results: Epidemiology: 793 pts were included, 565 being under 70 years old (mean 54), 228 over 70 years old (mean 76). There were more men in the elder group (67% vs 54%, this being explained by some differences in tumor type (more prostate cancer). Proportion of metastatic pts was not different (78 vs 79%) but metastatic sites were not the same, especially bone mets (70 vs 55%). Fewer pts were currently treated with chemo or radiotherapy in the elder group. Median WHO performance status was worse in elderly pts (3 vs 2). Characteristics of pain: Of note, characteristics of PP and BTP (pain location, nociceptive or neuropathic pain, intensity for PP and BTP, number of BTP episodes) were not different between the 2 groups. Pain treatment: Almost all the pts received opioids in both groups for PP and BTP, while elder pts were treated less frequently with specific drugs for neuropathic pain (antidepressant and anti-epileptic), and psychological support was less likely offered to them (36 vs 48%) Conclusions: Characteristics of PP and BTP in cancer pts are not influenced by pts age. Progresses have been made as elder pts receive opioids as often as younger ones, but improvements are still needed concerning the treatment of neuropathic pain and psychological support in elderly pts.

No significant financial relationships to disclose.
Early detection of cardiotoxicity during chemotherapy using biomarkers
Authors: Lenihan D. J. , Massey M. R. , Baysinger K. , Steinert D. , Fayad L. , Yusuf S. W. , Chiu A. , Durand J. , Yeh E. T.
Published: March 2020

19521

Cancer chemotherapy (CHEMO), especially anthracycline-containing regimens, may result in heart failure and left ventricular dysfunction (LVD) due to cardiotoxicity (CVTx). The ability to detect CVTx currently utilizes techniques to assess LVD, such as MUGA or echocardiography (Echo), which have substantial limitations and only detect LVD well after it occurs. Cardiac biomarkers, troponin (Trop I) and B-Type Natriuretic Peptide (BNP) are well established for detecting myocardial injury and LVD in patients without cancer. Limited evidence suggests that these may be important predictors of subsequent CVTx during CHEMO, but these markers have not been systematically investigated prospectively. Methods: Patients undergoing anthracycline-containing combination CHEMO were evaluated at baseline with: history and physical; electrocardiogram; Echo; and BNP and Trop I. Biomarkers were repeated before and after up to 6 cycles of CHEMO. ECHO was repeated after 6 cycles or at 6 months from baseline. Cardiac events (heart failure, LVD, sudden death, or arrhythmia) were documented, if present. Results: To date, 111 (53M/58F) patients, age 56±14 (mean±SD), with either lymphoma (n=39, 35%), sarcoma (n=60, 54%), or breast cancer (n=12, 11%) were enrolled. At least one traditional cardiac risk factor was identified in 77 (69%) and 2 or more risk factors noted in 46 (41%). Baseline ECHO parameters including ejection fraction (EF) and biomarkers were normal. With CHEMO, the mean post CHEMO BNP value (pg/ml) for the group did not change significantly; however, in the 8 patients with cardiac events, the BNP post CHEMO was elevated. The Trop I values were not abnormal except in 2 patients with events. Conclusion: Preliminary data collected to date indicates that BNP values during CHEMO remain normal unless cardiac events occur. Additionally, elevated BNP levels appear to detect CVTx, but LVEF did not. Furthermore, patients receiving CHEMO frequently have cardiac risk factors that may promote CVTx.

[Table: see text]

No significant financial relationships to disclose.
Quality of life following amputation or limb salvage in patients with lower extremity sarcoma
Authors: Mason G. E. , Aung L. , Gall S. , Meyers P. A. , Sklar C. , Butler R. , Healey J. H. , Gorlick R. G.
Published: March 2020

19530

Background: Currently between 80–90% of patients with lower extremity sarcoma undergo limb salvage procedures. A few trials show that the functional quality of life is significantly higher for limb salvage surgery compared to patients with amputation. While taking quality of life and psychological consequences into account it would seem that limb salvage would be the procedure of preference; however, this difference has yet to be demonstrated in previous studies. Methods: Eighty-two long-term survivors of lower extremity sarcoma were studied to make a comparison of the overall quality of life in limb salvage and amputation patients. Forty-eight patients with limb salvage (age 14–49 years) and thirty-four patients with amputations (age 15–49 years) were studied who were at least one-year post- surgical procedure. Sensitive psychometric measures such as self-report questionnaires and visual analog scales were used to assess psychological consequences and quality of life. Results: The overall quality of life of patients with the limb salvage was significantly higher than patients with amputation (p-value < 0.01). For the quality of life questionnaire, the limb salvage patients had a higher mean value in every domain except parent-child relations. The domains that showed a significant difference between patients with limb salvage and patients with amputations are material well being, occupational relations, creative-aesthetic behavior, and sports activity. Conclusions: For patients with lower extremity sarcoma, the psychological quality of life is better for those who received the limb salvage procedure. The significance of this study is that it one of the first to show that there is a direct benefit to limb salvage surgery as compared to amputation in regards to several psychological factors and total quality of life.

No significant financial relationships to disclose.
Weight change among breast cancer patients receiving chemotherapy: A retrospective analysis
Authors: Nair B. P. , Khalil O. , Phooshkooru V. R. , Hutchins L. F.
Published: March 2020

19535

Background: Weight gain occurs in patients with early stage breast cancer receiving chemotherapy. The etiology is unknown. Most pre-menopausal patients receiving chemotherapy enter menopause during the course of treatment. We explored the relation between weight gain and development of menopause in breast cancer patients. We hypothesized that, among breast cancer patients receiving chemotherapy, those in the pre/perimenopausal group will gain more weight compared to postmenopausal group in the first 2 years. Methods: The electronic database at University of Arkansas was queried for breast cancer patients treated with chemotherapy between May 1992 and Nov 2003. Age, chemotherapy and weight at multiple time points (diagnosis, 6, 12, 24 and 60 months) were obtained. The mean weight changes across these time points were then calculated for the entire population and also after categorizing by age. Age was used as a surrogate for menstrual status. Women aged >=50 yrs were considered postmenopausal, those <50 yrs were considered pre or perimenopausal. Results: 617 patients were included in the analysis. There were 371 patients in the >=50 age group and 246 patients in the <50 age group. The average baseline weight for the entire population was 75.21 kg: 74.44 for women <50 yrs and 75.71 for women >= 50 yrs. Patients <50 yrs of age gained weight in the first 2 yrs: 1.11 kg weight in the 1st year and 0.65 kg in the second yr. This was followed by loss of 1.19 kg over next 3 yrs which paralleled the loss of weight in the >=50 group. The mean weight of the >=50 age decreased by 0.27 kg in the first 2 years and then by 1.16 kg over the next 3 yrs following chemotherapy. Conclusions: Pre/perimenopausal breast cancer patients in our study gained weight, while postmenopausal patients had slight weight loss during the first 2 years. These findings imply that onset of menopause itself may be playing a significant role in weight gain among pre/perimenopausal breast cancer patients receiving chemotherapy.

[Table: see text]

No significant financial relationships to disclose.
Randomized study of early intervention compared to standard intervention with darbepoetin-alpha (DA) for chemotherapy-induced anemia (CIA) in early stage breast cancer (ESBC)
Authors: Blakely L. , Schwartzberg L. S. , Henry D. , Sabbath K. , Fu D. , Epperson A. , Fortner B. V.
Published: March 2020

19538

Background: Dose dense chemotherapy (DDC) with sequential doxorubicin/ cyclophosphamide followed by paclitaxel Q 14 days has an established place in the treatment of ESBC. However, moderate/severe CIA is a common consequence and therapeutic intervention is frequent. We sought to determine if early intervention at the onset of anemia with DA could reduce the emergence of more severe anemia during therapy and maintain quality of life compared to later intervention. Material and Methods: Non-iron deficient (ferritin > 50) patients (pts) with hemoglobin (Hb) levels >11.0 g/dl scheduled to receive adjuvant or neoadjuvant DDC for ESBC were recruited. Pts were randomly assigned prior to chemotherapy to initiate treatment with DA 200 μg q2w SQ when Hb < 11.5 g/dl (early intervention, EARLY), or DA 200 μg q2w SQ when Hb < 10.0 g/dl (standard intervention, STD) with end of treatment defined as 14 days after the last cycle of chemotherapy. Dose escalation for inadequate response of < 1 g/dl after 6 weeks of DA and dose withholding/reduction for Hb >13 g/dl were pre-specified. Results: The complete sample of 149 pts have been accrued (median age of 53.1, range 28.7 - 74.5). Analysis of fatigue ratings show a trend towards lower fatigue scores in EARLY at Hb nadir, and at end of study,(ANOVA, Group x Time interaction, p=.07). Discussion: Early intervention with DA significantly reduces the risk of developing moderate/severe CIA and increases time spent in the target range during DDC for ESBC.

[Table: see text]

No significant financial relationships to disclose.
The role of reduced glutathione on oxaliplatin-induced neuropathy in colorectal cancer patients
Authors: Lelli G. , Romano G. , Ardito R. , Bochicchio A. , Capobianco A. , Coccaro M. , Di Leo P. , Tartarone A. , Romano C. , Calvi N. , Lorusso V.
Published: March 2020

19539

Background: Peripheral sensory neuropathy is a common side-effect of oxaliplatin based chemotherapy. The neuropathy is cumulative and dose-related. Symptoms include sensory ataxia and dysesthesia of the limbs, mouth, throat and larynx, and may be exacerbated by exposure to cold. Studies suggest that Glutathione (GSH) is neuroprotective against oxaliplatin-induced neuropathy. Methods: From Jan. 2004, 83 consecutive colorectal cancer patients (pts) elegibile to oxaliplatin-based regimen were treated with GSH 1500 mg/mq over a 15-minute infusion period before oxaliplatin. Treatment-related toxicity was evaluated based on National Cancer Institute (NCI) Criteria. Results: After four cycles of chemotherapy, 5 pts (6%) experienced G1 neurotoxicity. After eight cycles, 2 pts (2.4%) experienced G2 sensory neuropathy (duration < 7 days) and 8 (9.6%) pts G1. After 12 cycles, G3 sensory neuropathy was observed in 2 pts (2.4%), G2 in 8 (9.6%) and G1 in 11 pts (13%). Neither G4 sensory neuropathy was registered nor treatment interruption was required. Conclusions: These findings suggest that use of GSH may protect from oxaliplatin-induced neuropathy. In fact, in our series, only 2 (2.4%) pts experienced severe paresthesia interfering with daily activities and none hade permanent sensory loss. However, only a well designed randomised controlled study will definitely prove the protective effect of GSH on oxaliplatin induced neurotoxicity.

No significant financial relationships to disclose.
Hematologic outcomes of epoetin-alpha-treated cancer patients based on initial intervention of Hb <10 compared to Hb 10–11 g/dL: Results from a prospective observational study
Authors: Wang Q. , Chen E. , Larholt K. , Bookhart B. , McKenzie R. , Tak Piech C.
Published: March 2020

19542

Background: Current guidelines recommend consideration of epoetin alfa (EPO) therapy for chemotherapy-induced anemia (CIA) when Hb <11 g/dL (National Comprehensive Cancer Network) or Hb < 10g/dL (ASCO/ASH). To evaluate clinical outcomes in EPO-treated patients initiated at Hb < 10 v. 10–11 g/dL, an analysis was conducted of clinical outcomes from practice settings. Data were analyzed from the Dosing and Outcomes Study of Erythropoiesis-Stimulating Therapies (D.O.S.E.) Registry, an ongoing, prospective registry collecting data on real-world practice patterns. Methods: Data from 29 U.S. hospital and community-based outpatient practices were assessed from 1/04–10/06. Chemotherapy-treated adult patients with a non-myeloid malignancy, baseline anemia (Hb < 11 g/dL), receipt of at least two EPO doses, and study completion were included. This analysis stratified patients based on Hb level at EPO initiation. Outcomes assessed included proportion of patients requiring RBC transfusion, mean treatment duration, and proportion of patients achieving an Hb = 11 g/dL. Results: 245 patients were eligible for analysis. 97 patients were initiated at a Hb < 10 g/dL and 148 patients were initiated at Hb 10–11 g/dL Baseline characteristics (age, gender distribution, weight, platinum-based therapy, Karnofsky score, primary tumor type) were similar except baseline Hb (9.4 g/dL v. 10.5 g/dL). Treatment duration was similar in both groups at approximately nine weeks. Transfusion outcomes and time to NCCN target Hb level (Hb =11 g/dL) are described in the table . Conclusions: This ongoing observational study demonstrated over two-thirds of patients achieved NCCN target Hb = 11 g/dL. Additional benefits for the patients initiated at Hb 10–11 g/dL were a shorter time to NCCN target Hb and a lower proportion of patients requiring transfusions. These results support the use of EPO for patients with chemotherapy-induced anemia and Hb < 11 g/dL.

[Table: see text]

No significant financial relationships to disclose.
Predicting bacteraemia following chemotherapy administration in patients with hematological cancer (HC)
Authors: Moreau M. , Schwarzbold A. , Klastersky J. , Georgala A. , Muanza F. , Aoun M. , Ferrant A. , Bron D. , Paesmans M.
Published: March 2020

19543

Background: Infections cause important morbidity and mortality in patients undergoing treatment for cancer. The type and the intensity of chemotherapy play an important role in the risk of infection which manifests itself most often as febrile neutropenia (FN) but regimen-specific risks are not well defined. Since bacteraemia is associated with increased mortality, we tried to determine predictors of it and to validate a classification of aggressiveness of a given chemotherapy regimen (CR) to be used in a risk prediction model in patients with HC. Methods: Patients older than 16 years, diagnosed with HC of any type were prospectively enrolled and followed at the “Institut Jules Bordet” and at the “Cliniques Universitaires Saint-Luc (UCL)” between 2001–2005. Out of the 266 patients, 22.9%, 43.6% and 33.5% were followed respectively during one cycle, 2 to 4 cycles and more than 4 cycles, totalizing 1053 cycles. Relevant patient’s information were collected at the beginning of the first cycle. Before each cycle, the CR score was computed, a blood examination performed and the temperature measured. Bacteraemia was defined according to IDSA criteria. FN was defined as a neutrophil count < 500/μl and fever. Generalized Estimating Equations (GEE) was used for the analysis. Results: Among 1017 evaluable cycles, 148 (14.5%) were followed by an episode of bacteraemia. Among the cycles with FN, 35.5% had bacteraemia. In the final model, adjusted for antimibrobial prophylaxis (R2=0.22), the CR score was the most important predictor of bacteraemia (OR 4.2 [95% CI, 2.3–7.6]), for patients given an aggressive regimen compared to the others. The other predictors associated with bacteraemia were: underlying disease (3.2 [1.9–5.2]), a baseline monocytopenia (<150/μL) (2.7 [1.6–4.3]), a baseline CRP >10 mg/L (2.1 [1.2–3.7]), the first cycle of patient’s treatment (0.3 [0.2–0.7]) and the administration of immunosuppressive agents (2.2 [1.2–4.0]). Conclusions: Bacteraemia was frequent in patients with HC undergoing myelosuppressive chemotherapy, especially in patients with FN. The CR plays an important role but further studies are needed to investigate yet unidentified additional risk factors. Grant given by the FNRS in Belgium (“Fonds National pour la Recherche Scientifique”)

No significant financial relationships to disclose.
The expanded role of palliative procedures with minimally invasive tumor ablation techniques
Authors: Miner T. J. , Gaydos-Gabriel J. , Kim W. , Mayo-Smith W. , Dupuy D.
Published: March 2020

19548

Background: To effectively and appropriately manage the debilitating symptoms of advanced cancer, physicians must balance the potential promise of palliative interventions against requirements to avoid toxic or futile therapy. Ablative technologies are increasingly used for the local destruction of tumors. This study examines the outcomes of ablative procedures performed with palliative intent. Methods: Minimally invasive ablative procedures (microwave and radiofrequency) to explicitly palliate symptoms of advanced cancer were identified from all procedures performed. Patients were observed for >90 days or until death. Results: There were 175 palliative ablative procedures performed in 129 patients from 1999 to 2004. Ablations were performed most commonly for pain (90%) caused by metastatic (90%), locally advanced (5%), and locally recurrent (5%) disease. Primary malignancies treated were lung (31%), colorectal (14%), renal (11%), breast (9%), sarcoma (9%) and other (26%). Symptom improvement or resolution within 30 days was achieved in 69% (89/129). Median duration of symptom control was 315 days. Recurrence of the primary symptom occurred in 46% (59/129) while treatment of additional symptoms was needed in 22% (29/129). Palliative ablative procedures were associated with postoperative morbidity (25%) and mortality (7%). A postoperative complication reduced the probability of symptom improvement to 25% (p<0.001). Effective symptom relief was associated with improved overall survival (median 408 days vs. 161 days, p<0.001). Conclusions: In carefully selected patients, relief of symptoms following palliative ablative procedures can be expected, but new or recurrent symptoms limit durability. As observed in other palliative procedures, potential benefits are minimized by postoperative complications. Optimal management for these patients with advanced cancer, who are often not suitable candidates for operation, requires the highest level of multidisciplinary care.

No significant financial relationships to disclose.
Role of IL-1β and IL-4 in 5-fluorouracil- induced intestinal mucositis in mice
Authors: Mota J. S. , Soares P. M. , Brito G. A. , Cunha F. Q. , Souza M. L. , Ribeiro R. A.
Published: March 2020

19551

Background: Intestinal mucositis is a frequent side-effect associated to 5-fluorouracil (5-FU) clinical use. The participation of cytokines in the 5-FU- induced intestinal mucositis was not completely elucidated. We evaluated the role of IL-4 and IL-1β in 5- FU induced- intestinal mucositis in mice. Methods: Wild-type C57BL/6 mice or IL-4 deficient mice (-/-) were treated with 5-FU (450 mg/Kg, i.p.). Other group were treated with the soluble receptor IL-1Ra (100 mg/Kg, i.p., per day) or saline. Then, received the 5-FU (450 mg/Kg, ip). After three days, animals were sacrificed and pieces of duodenum (D), jejunum (J) and ileum (I) were harvested for assessment of epithelial damage by morphometry, myeloperoxidase (MPO) activity and cytokines (both in duodenum) quantification by ELISA. Statistical analysis was performed with ANOVA and Bonferroni test. Significance was set at p<0.05. Results: 5-FU induced a significant (p<0.05) epithelial intestinal damage (reduction of villus height/crypts depht reason) in all segments (duodenum-C= 3.3±0.2, 5- FU= 1.0±0.1; jejunum-C= 2.3±0.2, 5-FU= 1.0±0.1; ileum-C= 2.1±0.1, 5-FU= 0.7±0.1), increased MPO activity (n° neutrophil/mg of tissue) (C= 663.5±76.6, 5- FU= 3579±492) and cytokines concentration (pg/ml) (IL-1β: C= 134.8±31.9, 5-FU= 280.3±41.5; KC: C= 123.9±27.3, 5-FU= 177.2±28.2; TNF-a: C= 9.9±0.4, 5-FU= 12.1±1.8). IL-1Ra protected all segments from 5-FU- induced intestinal injury (D= 1.7±0.1, J= 2.0±0.1, I= 1.1±0.1), reduced MPO activity (2061±308) and cytokines concentration (IL-1β= 8.6±41.7; KC= 100±17.1; TNF-a= 7±.1.1). IL4 -/- presented with less epithelial intestinal damage (D= 2.9±0.2, J= 2.0±0.2, I= 1.4±0.1), less MPO activity (1702±315) and cytokines concentration (IL-1β:=86.5± 29.6; KC=105.6± 21.6, TNF-a:=7.4±0.5) . Conclusions: Our data suggest that IL-4 and IL-1β participates in the 5-FU induced- intestinal mucositis in mice.

No significant financial relationships to disclose.
Randomized trial to assess bone mineral density (BMD) effects of zoledronic acid (ZA) in postmenopausal women (PmW) with breast cancer
Authors: Tevaarwerk A. , Stewart J. A. , Love R. , Binkley N. C. , Black S. , Eickhoff J. , Mulkerin D. L.
Published: March 2020

19558

Introduction: Osteoporotic fracture represents a major source of morbidity in PmW. Breast cancer patients can be at additional risk because of treatment related estrogen deprivation. The favorable effects of bisphosphonates in osteoporosis and potential reduction of metastases warrant evaluation of ZA in PmW at high risk for breast cancer relapse. We assessed whether ZA 4 mg IV every 12 weeks x 4 doses was associated with an increase in BMD. Secondary objectives included defining ZA’s toxicity profile in this setting, and assessing for differences in overall cancer relapse. Methods: PmW with node positive or stage III breast cancer diagnosed less than 5 years earlier were randomized to ZA or observation. BMD was assessed by dual energy xray absorptiometry (DXA) for all subjects at 0 and 12 months. A toxicity evaluation was performed pre- and post-treatment for patients receiving ZA. Study endpoint occurred when subjects completed the DXAs, had disease progression or declined further treatment. We calculated change in BMD between 0 and 12 months at the L1–4 spine and femur neck. Results: 66 women have enrolled since 2000; 49 women have completed DXAs at 0 and 12 months (observation 23, ZA 26). Median age was 52 (range 40–81 yr), median ECOG performance status was 0 (range 0–1), and most women received concurrent tamoxifen (observation 74%, ZA 61%). Over 12 months, L1–4 spine BMD decreased in the observation arm (-0.006 ± 0.034 g/cm2) and increased in the ZA arm (p<0.001; 0.050 ± 0.042 g/cm2). No significant BMD change occurred at the femur neck. Only three grade 3 events occurred (2 arthralgia, 1 myalgia). Side effects were mild and transient, but as frequent as 87% following dose 1. The most common side effects were fatigue, myalgia and arthralgia. No clinically significant changes in creatinine or calcium occurred. Osteonecrosis of the jaw was not observed. Of the 66 women enrolled, 7 have relapsed (observation 4, ZA 3) but time since diagnosis is less than 10 years for most patients. Conclusions: ZA administered every 12 weeks for 4 doses leads to a statistically and clinically significant change in BMD at the lumbar spine. Toxicity was mild but common. There are as yet no significant differences in cancer relapse.

No significant financial relationships to disclose.
Patient and parent longitudinal reports of quality of life in children and adolescents with osteosarcoma
Authors: Hinds P. S. , Gattuso J. S. , Billups C. , Rivera C. , Quintana J. , Daw N.
Published: March 2020

19562

Children and adolescents being treated for osteosarcoma are likely to experience physical, emotional, functional and possibly cognitive changes during the course of their treatment. The aims of this prospective study were to assess the effect of treatment on patients’ quality of life (QoL) at diagnosis and during therapy, compare patient and parent QoL reports, and examine relationships between patient QoL and tumor histologic response to preoperative chemotherapy and event-free survival (EFS) in children and adolescents in treatment for osteosarcoma. Newly diagnosed patients with localized disease completed three established patient reports (Symptom Distress Scale, and PedsQL v.3 and v.4). Parents completed two parent reports (PedsQL v.3 and v.4). QoL evaluations were done at diagnosis, prior to definitive surgery (Week 12), and postoperatively during treatment (Week 23). Sixty-two of 72 eligible patients and their parents completed QoL measures. Symptom distress (SD) decreased in 85% of patients from baseline to Week 12 (with 8/10 symptoms significantly improved) and from baseline to Week 23 in 74% of patients. Improvements in most domains of the PedsQL v. 3 were noted by patient and parent reports from baseline to Weeks 12 and 23 except for the nausea domain. Patient and parent reports differed, with parents reporting lower QoL scores on v. 3 than did patients, particularly in the domains of treatment anxiety, cognitive problems, and communication. QoL scores did not differ by patient gender but did by age in certain domains. Patients reported significant improvements in physical and emotional functioning from baseline to Weeks 12 and 23 using the PedsQL v.4. Parents reported significant improvements in emotional functioning from baseline to Weeks 12 and 23 using the PedsQL v.4. QoL scores were not associated with tumor histologic response or EFS. Significant improvements in QoL domains and in symptoms from diagnosis to Week 12 and to Week 23 were documented in both patient and parent reports. Treatment contributed to improvements in physical and emotional functioning and in symptoms except for nausea. QoL was not related to histologic response or EFS.

No significant financial relationships to disclose.
Is there a benefit to having a clinical oncology pharmacist on staff at a community oncology clinic?
Authors: Ruder A. D. , Smith D. L. , Madsen M. T. , Kass F. H.
Published: March 2020

19570

Background: The John Marsh Cancer Center is an ambulatory oncology clinic located in Hagerstown, MD. In 2004, an on-site clinical oncology pharmacist was hired to help manage therapies and control cost. The objective was to evaluate the clinical interventions and assess the impact of consultations by the clinical oncology pharmacist to patients during therapy. Methods: This was a retrospective descriptive analysis of previous clinical interventions by the clinical oncology pharmacist from September 4, 2004 to October 27, 2006. This study involved a diverse patient population with different tumor types and/or disease states. The evaluation comprised two different categories: drug related problems (DRPs) and consultations, with several sub-categories. The DRPs included medication reconciliation, dosing, and adverse effect management and prevention. Consultations incorporated drug information questions, patient visits, and patient education sessions. The information was extracted from an online documentation program linked to medical charts and analyzed to determine the impact of a clinical oncology pharmacist on staff at the cancer center. Results: A diverse population of 199 patients was identified. Diagnoses included solid tumors 89%, hematological malignancies (3%), and miscellaneous diseases (8%). The 583 clinical interventions documented totaled 5,705 minutes, at an average of 10 minutes per intervention. Of the 583 interventions, 205 were DRPs, including 22 dosing, 52 medication reconciliations, and 131 adverse events. A total of 378 consultation interventions were documented, including 25 drug information questions, 124 patient visits, 143 patient education sessions, and 86 patient follow-ups. The on-site clinical oncology pharmacist saved $210,000 by admixing chemotherapy. Implementation of a carboplatin skin-testing protocol saved over $3,000 by preventing hypersensitivity reactions. Patient and colleague satisfaction surveys found the pharmacist to be a valuable asset with overall positive ratings of 95% and 98%, respectively. Conclusion: Analysis of clinical interventions, cost-savings, and feedback from patients and colleagues confirmed beneficial services provided by a clinical pharmacist in an outpatient oncology center.

No significant financial relationships to disclose.
Differences in lung cancer symptom severity by tertiary cancer center vs. centers treating underserved patients
Authors: Palos G. R. , Shi Q. C. , Mendoza T. , Mobley G. , Zhang Y. , Valero V. , Hurley J. , Wang X. S. , Cleeland C. S.
Published: March 2020

19577

Background: Understanding how differences in treatment site and ethnic/racial background affect the severity and outcomes of symptoms related to advanced lung cancer is critical to providing optimal symptom management. This analysis investigated the differences in the severity of symptoms among patients receiving treatment for advanced non-small cell lung cancer (NSCLC) at three different treatment centers. Methods: We compared changes in ratings of 139 patients diagnosed with NSCLC over the course of their chemotherapy regimen for symptoms and their interference on daily activities. Eligible patients had to be diagnosed with Stage III or IV NSCLC and treated at Jackson Memorial - Dade County, LBJ - Harris County or The University of Texas M. D. Anderson Cancer Center. Data were collected using telephone and pen-paper versions of the M. D. Anderson Symptom Inventory Lung Chemotherapy Module. Mixed modeling analysis was used to examine the differences in self-reported symptom severity between black, non-Hispanic, Latino/Hispanic and white, non-Hispanic patients. Results: A total of 56 patients from all sites, matched by age and gender, were included in this sub-analysis. Because this was a relatively small sample, we combined the non-Hispanic, black (27%) and Latino/Hispanic (14%) groups to form the minority group vs. the majority group (59%). Median follow-up was 24 weeks. Inclusion of the treatment site in the model resulted in losing the effect for ethnicity for the majority of symptoms. Significant higher ratings were found for fatigue and drowsiness in white, non-Hispanic patients when compared to the minority group. We found that treatment site (tertiary vs. center treating underserved) was a significant predictor for differences in symptom severity scores. Greater symptom severity ratings were found in patients seen at centers treating the underserved for pain, sleep, fatigue, nausea, shortness of breath, appetite, drowsy, dry mouth, and numbness. Conclusions: These findings suggest that receiving treatment at a center caring for the medically underserved is associated with greater symptom burden in patients with advanced lung cancer. These results underscore the need for additional studies.

No significant financial relationships to disclose.