bluuebunny/crossref_metadata_2025 huggingface dataset:
Snk/Plk2 CpG methylation in patients with multiple myeloma
Authors: Dasoula A. , Hatzimichael E. , Dranitsaris G. , Benetatos L. , Syed N. , Vassou A. , Stebbing J. , Crook T. , Bourantas K.
Published: August 2020

e19532

Background: We previously showed that polo like kinase 2 (Snk/Plk2) is subject to methylation-dependent transcriptional silencing in a very high frequency in Burkitt lymphomas. Here, we have examined CpG methylation in Snk/Plk2 in a well-characterized series of multiple myeloma (MM) patients. Methods: Bone marrow samples from individuals with MM were obtained at diagnosis and in 5 cases at disease progression as well. Genomic DNA was isolated and bisulphite modification was performed using commercially available kits. The methylation-specific polymerase chain reaction (MSP) was employed to study its methylation status. Control methylated and unmethylated genomic DNAs were included in each experiment. Ten bone marrow samples from individuals proven to have no haematological malignancy, served as negative controls. Logistic regression analyses were used to measure the association between gene methylation and the development of advanced disease (DS≥II), extramedullary disease, bone disease, anemia (Hb 10 mg/dl), serum albumin and beta 2 microglobulin levels. Results: We analyzed the methylation of Snk/Plk2 in 45 cases of MM (24 male, 21 female, mean age 66.4 years ±12.4). Classical cytogenetic analysis was available in 30/45 patients and none of them was found to have chromosome 13 abnormalities. No sample from the control population was found methylated. The Snk/Plk2 promoter was found to be methylated in 27/45 patients (60%). Median survival of patients in whom the Snk/Plk2 CpG island was methylated was 7.1 years compared to a median survival of 8.8 years for unmethylated. However Snk/Plk2 methylation was not a predictor of excess mortality (HR=0.6, p=0.5), bone lytic lesions (OR=0.56, p=0.3), anemia (OR=0.5, p=0.3) or advanced stage as defined above (OR=0.8, p=0.7). Conclusions: Snk/Plk2 DNA Methylation is a frequent event in patients with multiple myeloma. There was no association between the methylation status of the gene and relevant clinical parameters. Further evaluation in a larger sample of patients is needed in order to better define the prognostic and clinical value if any of Snk/Plk2 methylation in MM.

No significant financial relationships to disclose.
A retrospective chart review study of relapsed or refractory multiple myeloma (MM) patients (Pts): A look into historical treatment (Tx) patterns
Authors: Zaman F. , Reece D. E. , Teixeira B. L. , Yoong K. , Camacho F. , Plante R. K.
Published: August 2020

e19535

Background: New Tx options have become available on the market or as investigational agents in Canada for relapsed/refractory MM in the last few years. These new Tx options include IMiDs [thalidomide, lenalidomide (Revlimid)] and a proteosome inhibitor [bortezomib (Velcade)]. These new agents are changing both the Tx patterns as well as the clinical outcome of this disease. New combination regimens of both new agents and older generic drugs are also being investigated. Methods: This retrospective analysis included all relapsed/refractory MM Pts who initiated drug Tx between Jul-06 and Jun-07 at Princess Margaret Hospital, Toronto, ON. Historical data collection focused on prior Tx (types), duration and efficacy. Results: This analysis included all prior historical Tx data Dec-96 to Jul-07) from 151 Pts. 62% of Pts were male. Time from diagnosis to 1st initial Tx was 1.7 (SD±4.2) months. Of the 25 Pts who had cytogenetics analyzed by FISH, 6 Pts had deletion 13q, 4 Pts had translocation involving chromosome 14 [including partner gene translocations on chromosomes 4 (2 Pts) and 11 (1 Pt)] and no Pts had deletion p53. 76.8% of Pts received at least 1 stem cell transplant (SCT) with 7.9% of Pts receiving 2 SCTs prior to current study Tx. Historical 1st line & 2nd line Txs, respectively, were cyclophosphamide ± steroid (14.6%, 28.3%), IMiD-based (17.2%, 40.2%), melphalan + prednisone (14.6%, 9.8%), vincristine + adriamycin + dex (69.5%, 5.4%), steroid monotherapy (23.8%, 22.8%), bortezomib based (0.7%, 15.2%), and other (6.0%, 6.5%). Overall best RRs (≥MR) during historical 1st & 2nd line Tx were 92.6% and 83.3% (≥ minimal response), respectively, with a corresponding 15.6% & 11.9% combined CR + near CR rate, respectively, across all regimens reported. Historical median TTP following 1st, 2nd, and 3rd line of Tx were 21.5 (95% CI: 18.9, 24.3), 20.2 (95% CI: 16.9, 22.8), and 10.0 (95% CI: 5.5, 16.6) months, respectively. Conclusions: This is the first known historical analysis of real world MM Txs in Canada from a large tertiary centre. Historical data suggests the common use of older drugs such as alkylating agents. This usage pattern may be different than in other countries where the accessibility of newer agents to treat MM is easier than in Canada.

[Table: see text]
Autologous stem cell transplant in peripheral T cell lymphomas: Single institution 10-year retrospective analysis
Authors: Vigil C. E. , Ayala E. , Sokol L.
Published: August 2020

e19538

Background: Peripheral T-cell lymphoma is a rare entitydisease, compromising 10% of non-Hodgkin's lymphoma worldwide and 5% of all lymphoid neoplasms in the United States. The long-term survival of conventional therapies has led the exploration of alternatives. High-dose chemotherapy followed by autologous haematopoietic stem cell transplantation, has been explored in recent years with little experiences. We are reporting our single-institute data in this population. Methods: A retrospective analysis on patients with diagnosis of peripheral T-cell lymphoma receiving autologous stem cell transplant was conducted (January 1997 to July 2008). The patients were stratified according to their International Prognostic Index (IPI), disease status at the time of transplant and histology type. Results: Twenty-nine subjects were identified, with a median age of 51; 13 patients had Anaplastic T cell, 18 patient had PTCL-nos, and 6 patients with angioimmunoblastic T cell lymphoma. Seventeen patients (58.62%) presented with an aa IPI score greater than 2.4 patients were in complete remission, 15 at first relapse, 4 in greater than 1 episode, and 6 with refractory disease at the time of transplantion.Kaplan Meier overall survival (OS) 72 and relapse free survival (RFS) was 62 at 1 year respectively. A multivariate analysis and new risk stratification based on the IPI score system and disease status at time of transplant were employed. We found that the lower risk category demonstrated a higher likelihood of longer survival HR 3.4. However, such outcome was not statistically significant (p = 0.1360). Conclusions: The status at time of transplant with new methods for evaluation of minimal residual disease may help in assessing outcome. Larger prospective studies investigating innovative regimens is warranted.

No significant financial relationships to disclose.
Analysis of prognostic factors in patients with EBV positive diffuse large B cell lymphoma of the elderly
Authors: Morales D. , Beltran B. , Hurtado de Mendoza F. , Riva L. , Quiñones P.
Published: August 2020

e19542

Background: EBV positive diffuse large B cell lymphoma of the elderly is a new entity included in the Fourth edition of WHO Classification. It usually affects elderly patients and has a poor survival. It believed to be related to immunesenescence. Aim: The goal of this study was to evaluate clinical characteristics and survival of EBV positive diffuse large B cell lymphoma of the elderly from Peruvian patients. Methods: Between January 2002 and June 2008, eleven patients with EBV positive diffuse large B cell lymphoma of the elderly were included in the analysis. All cases were positive to the presence of EBV encoded RNA (EBER) by CISH and CD20 and/or Pax-5 expression by immunohistochemistry.Clinical data were reviewed retrospectively and patient's biopsies were analyzed for the immunohistochemical expression of BCL6, CD10, CD30 and MUM-1/IRF4 by tissue microarray (TMA) technique.. The survival analysis was performed using the Kaplan - Meier method. Results: The mean age was 72 years old (range 34–85), only two patients had less than 70 years old. B symptoms occurred in 6/11 (54%); ECOG 0–2 ( n=3) and >2 (n=8). Stage: I (n=1), II (n=1), III (n=5) and IV (n=4). The IPI risk score was: low (n=1), low intermediate (n=1), high intermediate (n=5) and high (n=4). Extranodal disease occurred in 6/11 (54%) patients: pleura (n=2), suprarenal gland (n=1), stomach (n=1), cecum (n=1), bone (1), skin (1) and bone marrow (n=1). One was HTLV-1 carrier. Ten cases (83%) were of the Non-GC and 1 case was GC. Three cases were CD30 positivity. Index Prognostic model (age/B symptoms) for this entity was: 0 factors (n=0), 1 factor (n=7) with median survival 9 months; and 2 factors (n=4) with median survival of 1.5 months. Six patients had not received chemotherapy because they had bad status performance and 5 received CHOP-21 regimen. Overall response was 40%. Complete response (n=2), partial response (n=0) and progressive disease (n=3). Median survival was 6.4 months. Only one patient had a long survival (42.5 months). Conclusions: EBV positive diffuse large B cell lymphoma of the elderly was related to high IPI, poor ECOG, frequent extranodal disease, poor response to treatment and very short survival. It is the first report of this entity in a non-Asian population.

No significant financial relationships to disclose.
Correlation between expression of MCM6, a new proliferative marker, and treatment outcome in patients with Hodgkin's disease
Authors: Khodadad K. , Karimi S. , Esfahani Monfared Z.
Published: August 2020

e19547

Background: MCM6 is a proliferative marker, which in contrary to Ki67, is involved in all cell cycle phases, including early G1. We evaluated MCM6 expression in Hodgkin's disease (HD) patients in order to find any correlation between MCM6 expression and treatment outcome. Methods: Formalin-fixed paraffin-embedded lymph node specimens of 55 patients with HD treated with ABVD regimen (± radiotherapy) were assessed for MCM6 expression by IHC. The percentage of nuclear positivity in RS and mononuclear Hodgkin cells was evaluated in each case. Clinical data, response to treatment and relapse rates were obtained from patients’ medical records. These data were analyzed by SPSS software. Results: Mean MCM6 expression was 80.7% (ranging 35%-99%) with no significant difference between histology subtypes. In univariate analysis, MCM6 expression was not statistically significant for B-symptoms (P=0.27), sex (P=0.91), stage (P=0.18) and response to treatment (P=0.53), but was significant for age (P=0.008) (≤23 vs >23 yrs old). The MCM6 mean expression between relapsed and non-relapsed groups was marginally significant (21% vs 29.4%, P=0.057). In multivariate analysis, we evaluated MCM6 expression, B-symptoms, stage, response rate and age for relapse. None of risk factors were statistically significant predictor for relapse, including MCM6 expression (P=0.238), however, were significant regarding to response (P<0.001) and stage (P=0.048). We divided patients in 4 quartiles based on their MCM6 expression (Q1<74.25%, N=13, Q2=74.26–85.5%, N=14, Q3=85.6–91.75%, N=13, Q4>91.75%, N=12). Relapse and PFS were not significantly different between these quartiles (P=0.27 and P=0.83, respectively). Conclusions: Our study on a limited number of patients revealed MCM6 is not a strong predictor for treatment outcome in patients with HD. Our findings can be possibly explained by early G1 arrest of tumor cells and the role of cytokine production in pathogenesis of HD. We believe determining the accurate predictive role of proliferative markers needs to be focused on the markers which are exclusively involved in S phase.

No significant financial relationships to disclose.
Effect of dosing cycles on safety of denileukin diftitox (Dd) in cutaneous T-cell lymphoma (CTCL) patients: Integrated analysis of three phase III studies
Authors: Kim Y. , Beynon J.
Published: August 2020

e19557

Background: Dd is a novel IL-2 receptor-targeted recombinant fusion protein that is approved for treatment of persistent/recurrent CTCL expressing CD25. To date, Dd is the most extensively studied agent in CTCL. The safety of Dd was assessed with respect to dosing cycle in CTCL subjects in 3 large phase III studies: 93–04–10 (study 10), L4389–11 (study 11) and L4389–14 (study 14). Methods: Subjects received Dd doses of 9 or 18 mcg/kg IV daily for 5 days, repeating every 21 days for up to 8 cycles; study 11 also included a placebo arm. Subjects in studies 10 and 11 were CD25(+); study 14 also included CD25(-) subjects. Safety data from these studies were integrated and are presented by dosing cycle. Results: Table 1 shows a summary of all reported adverse events (AEs) by cycle for the 3 studies. For subjects completing at least 4 cycles of Dd treatment the incidence of any AEs was lower in the 3rd and 4th cycles as compared to the 1st and 2nd cycles and the incidence of AEs continued to decrease after cycle 4. Conclusions: In the studies analyzed, the incidence of AEs decreased with each subsequent treatment cycle for subjects receiving Dd.

[Table: see text]

[Table: see text]
Non-Hodgkin's lymphoma (NHL) patients at a VA medical center: Comorbidity and treatment
Authors: Srinivas S. , Cholankeril M. , Chang V. T. , Morales-Muyuela E. , Duque L. , Toomey K. , Kasimis B.
Published: August 2020

e19559

Background: We hypothesized that measures of comorbidity may help explain the number of treatments administered to patients with non-Hodgkin's lymphoma. Methods: We performed a retrospective, IRB approved protocol, using chart review of all patients diagnosed with non-Hodgkin's lymphoma at the VANJHCS from January 1, 1997 through December 31, 2008. Records were reviewed for demographic, clinical, pathological data, the number of chemotherapy regimens, radiation therapy, and total number of treatments and survival. We tabulated the Charlson Comorbidity Index (CMI), the Kaplan-Feinstein Comorbidity Index (KFI), the Cumulative Illness Rating Scale (CIRS), International Prognostic Index (IPI), and performance status (PS) were tabulated for 100 patients seen at a VA Medical Center. Results: There were 100 patients with median (M) age 62 years (27–89). There were 61 deaths (61%) with M survival(MS) 1068 days(13–3976). The M Stage was 1(0–4), M LDH was 204 IU/L (88–1905), M Hgb 12.3gm/dL (7.3–17.4), M Albumin was 3.8g/dl(1.2–5.4), M Zubrod Performance Status(PS) was 1(0–4) in 50 pts(50%). The M CMI was 6(1–12), M KFI was 3(1–3), M CIRS17 was 1.7(1–3.15). The M total number of systemic therapy regimens received was 1(0–4.5), M radiotherapy was 0(0–1) and the overall M total treatment regimens used was 1 (0–4.5). IPI was a significant predictor in the use of radiation therapy (p<0.054) but did not correlate with the use systemic therapy. The CMI was a predictor of the use of systemic chemotherapy (p<0.007), and the total number of treatments received (p<0.011), but not the KFI or the CIRS 17. The performance status did not predict for the number of treatments. In a Cox regression analysis, the number of treatments did not affect survival. Conclusions: This data provides evidence that one measure of comorbidity, the CMI, may partially explain the number of systemic therapy treatments, and total treatments received by NHL patients. Further work in larger groups of pts is warranted.

No significant financial relationships to disclose.
The clinicopathological spectrum of HIV-associated lymphoma: Eleven-year-experience in a general hospital in Peru
Authors: Vera L. , Reategui R. , Beltran B. , Morales D. , Capellino A. , Desposorio C. , Castillo J.
Published: August 2020

e19561

Background: The clinicopathological spectrum of HIV-associated lymphomas in developing countries has not been clearly defined. Thus, this study is aimed to describe these features in cases from a Peruvian population. Methods: This is a retrospective review of the clinical records of patients with diagnosis of HIV in our institution from March 1997 to March 2008. We reviewed 2502 clinical records. The statistical method was descriptive and survival was calculated using the Kaplan-Meier method. Results: Forty-eight patients with HIV-associated lymphoma were identified. Male:female ratio was 15:1. Median age was 42 years (range 27 to 70). 32 patients (67%) had clinical stage III-IV, B symptoms 35 (73%), the International Prognostic Index was low-risk 20 patients (42%), low-intermediate risk 15 patients (31%), high-intermediate risk 10 patients (21%) and high-risk 3 patients (6%). CD4 count lower than 100 cells/uL was 11 patients (23%). The CD4 count median was 184 cells/uL. The nodal localization in 27 patients (56%) was lightly higher. Forty-four cases (92%) were diagnosed with non-Hodgkin lymphoma (NHL) and 4 cases (8%) with Hodgkin lymphoma (HL). From the 44 NHL cases, 40 cases (91%) were of B-cell origin; 23 cases (57.5%) had diffuse large B-cell, 9 cases (22.5%) had Burkitt, 3 cases (7.5%) had plasmablastic, 2 cases (5%) had primary CNS, 2 cases (5%) had MALT and 1 case (2.5%) had primary effusion lymphoma. The remaining 4 cases (9%) were of T-cell origin; 3 cases (75%) had peripheral T-cell lymphoma NOS and 1 case (25%) was ALK-negative anaplastic large cell lymphoma. Only 16 patients (33%) were receiving HAART previously the diagnosis of NHL and 33 patients (68%) received any oncology treatment. Conclusions: This entity is aggressive and frequently has extranodal involvement. Also a high proportion of T-cells lymphomas are found. These findings are in concordance with one prior report of another general hospital from Peru.

No significant financial relationships to disclose.
Response of AIDS-related plasmablastic lymphoma (PBL) to bortezomib
Authors: Bose P. , Thompson C. L. , Gandhi D. G. , Ghabach B. S. , Ozer H.
Published: August 2020

e19562

PBL are a group of highly aggressive neoplasms originally described in the oral cavity and jaws of HIV-infected patients. An AIDS-defining illness, PBL comprises 2.6% of AIDS-related lymphomas. PBL are best distinguished by their unique immunophenotype. They are terminally differentiated B-cell neoplasms, and typically lack common B-cell markers but uniformly express plasma cell markers. We report the first case of PBL that responded to bortezomib. A 42-year-old male with newly diagnosed AIDS presented with nausea, vomiting, bloody diarrhea and epigastric pain. EGD with biopsy revealed a high-grade PBL of the stomach. Flow cytometry was negative for CD45 and all common epithelial, T-cell and B-cell markers, but was positive for CD138 and p63(VS38c). Karyotyping revealed t(8;14), amongst other abnormalities. PET/CT showed significant hypermetabolism in multiple thoracic and abdominal lymph nodes, the left lung, liver and several bones. The diagnosis was stage IVBE PBL. Highly active anti-retroviral therapy was begun. Anthracycline-based chemotherapy was avoided due to persistent hyperbilirubinemia. Bortezomib was then administered at a dose of 1.3 mg/m2 IV on days 1, 4, 8 and 11. PET/CT on day 7 showed a marked decrease in hypermetabolism after only 2 doses, signifying a dramatic treatment response. After a total of 4 doses of bortezomib, he unfortunately succumbed to severe septic shock before a repeat PET/CT could be obtained. The prognosis of PBL is poor, with a median survival of about 6 months in most series. The WHO classifies PBL as a variant of diffuse large B-cell lymphoma. Accordingly, CHOP and CHOP-like regimens have mostly been used. However, studies of their immunophenotype and molecular histogenesis suggest that PBL are more closely related to plasma cell neoplasms. Bortezomib is a proteasome inhibitor widely used in multiple myeloma and mantle cell lymphoma. We chose bortezomib based on our patient's poor performance status and immune function, the desire to avoid combination chemotherapy, and translocations involving the immunoglobulin heavy chain gene locus (8;14) similar to those seen in multiple myeloma(4;14, 14;16) and mantle cell lymphoma(11;14). A shift in the paradigm of treatment of PBL towards agents effective in plasma cell malignancies may be necessary.

[Table: see text]
Response to high-dose interleukin-2 (HD IL-2) therapy in patients with brain metastases from metastatic melanoma
Authors: Powell S. F. , Dudek A. Z.
Published: August 2020

e20007

Background: HD IL-2 has been shown to produce durable responses in patients with metastatic melanoma. The purpose of this study was to determine whether the University of Minnesota's outcomes were comparable to previously published data and to analyze subsets of patients to find further data on prognosis and response. Methods: A retrospective analysis was performed all adult patients with Stage IV melanoma treated with HD IL-2 from January 2000 to October 2008 at our institution. HD IL-2 was given I.V. every eight hours as a bolus over 15 minutes at a dose of 600,000 IU/kg. A maximum of 14 doses for each course was given. Results: A total of 15 patients with metastatic melanoma had been treated with HD IL-2 at our institution. Complete response (CR) was seen in 6.67% (N=1), partial response (PR) in 6.67% (N=1), mixed response (MR) in 6.67% (N=1), and stable disease (SD) in 13.33% (N=2). Average time to disease progression (TTDP) was 5.67 months in those with a PR or SD. Two patients with brain metastases had subsequently complete resolution of the brain lesions after HD IL-2 therapy. One of these patients has a CR and is disease free 34 months out from therapy. The other had PR and is currently alive with disease, but has no recurrence of the brain lesion after over 19 months. Twelve of the fifteen patients were able to receive 2 courses of therapy. On average patients tolerated 10.5 HD IL-2 doses with the first course and 8.8 doses with the second course. Common grade (G) 3 and 4 adverse events included hyperbilirubinemia (G 3 = 26.67%), hypotension (G 3 = 6.67%, G 4 = 6.67%), peripheral edema (G 3 = 26.67%), pulmonary edema (G 3 = 13.33%), and hypophosphatemia (G 3 = 6.67%, G 4 = 6.67%). Conclusions: The CR rate of 6.67% and TTDP in those with SD or a PR are comparable to previously published studies. Observed adverse events were also similar to other reports. HD IL-2 has typically been avoided in patients with brain metastases due to concern for neurologic complications from the capillary leak syndrome caused by treatment. We propose further evaluation of this ineligibility for HD IL-2, since carefully selected patients with brain metastases may derive benefit from this treatment.

No significant financial relationships to disclose.
Durable response of the triple combination of temozolomide, sorafenib, and bevacizumab as second-line therapy for patients with stage IV acral melanoma
Authors: Si L. , Chi Z. , Yuan X. , Cui C. , Sheng X. , Zhu Y. , Kong Y. , Kong Y. , Shen L. , Guo J.
Published: August 2020

e20010

Background: Temozolomide (TMZ) is an oral formulation of dacarbazine with improved central nervous system penetration. Sorafenib inhibits Raf kinase and vascular endothelial growth factor (VEGF) receptor. Bevacizumab is a monoclonal antibody targeted against VEGF. TMZ plus sorafenib has shown efficacy in advanced melanoma. The triple combination, chemotherapy plus the complementary inhibition of VEGF signaling, was hypothesized to have synergistic effects on acral metastatic melanoma. Methods: Eligible are refractory (previous one systemic regimen failed) acral advanced melanoma, measurable disease (RECIST). Treatment includes TMZ 200 mg/m2/d (days 1–5), bevacizumab 5 mg/Kg (days 1, 14) and sorafenib 400 mg/bid (days 1–28), repeated every 28days. VEGFR, PDGFR, EGFR and CD117 of tumor tissue were detected by Immunohistochemistry (IHC) assay and the DNA was abstracted and amplified by PCR assay and then sequenced to detect the mutation of C-KIT (exon11,13,17,18),B- RAF(exon11, 15) and N-RAS(exon1, 2). Progression free survival (PFS), overall survival (OS), response and toxicity were assessed. Correlation was analyzed between gene mutations, IHC results and clinical response. Results: 50 patients were planned to recruit. Till December of 2008, 11 patients all in M1c stage have been enrolled and evaluated. One patient has achieved complete response (CR) which has been lasting 5 cycles. One patient has achieved partial response (PR) with a 69% tumor reduction which has been lasting 3 cycles. One patient achieved PR with a 41% tumor reduction which has been lasting 6 cycles. 6 pts got stable disease (all tumor reduction, range: 4–21%) lasting > 2 cycles (range: 3–4 cycles); and 2 PD after 1 cycle. The toxicity was moderate. It's too early to assess survival. It seemed no correlation between positive IHC results and response. It could not be decided if there is correlation between gene mutation/IHC results and response/survival. Conclusions: The triple combination (TMZ, sorafenib, and bevacizumab) regimen preliminary achieved durable clinical response especially the patients with CR or PR. The regimen is safe and well tolerated. More data will be presented in ASCO.

No significant financial relationships to disclose.
Validation of a scoring system to improve life expectancy prediction in advanced cancer patients
Authors: Pourchet S. , Montheil V. , Ropert S. , Alexandre J. , Goldwasser F. , Durand J. P.
Published: August 2020

e20507

Background: Oncologists accurately estimates survival in 20% of cases for advanced cancer patients (J Clin Oncol 2005 23:6240–48), leading to prescribe chemotherapy until last weeks of life. This study aimed to develop a validated scoring system to prevent futility. Methods: Between January 2004 and November 2008, 500 evaluable out of 546 consecutive pts with uncurable metastatic solid tumors were entered in a prospective study. On a randomly selected derivation set, independent factors assessable at inclusion predicting 2-weeks survival by a multiple logistic regression, were assigned integer weights to develop a risk-index score, which was subsequently tested on a validation set. Results: On the derivation set (334 pts), predictive factors were: urea > 12 mmol/L (weight = 5; odds ratio (OR) = 3.72; 95% confidence interval (CI) = [1.59; 8.71], p = .002), Karnofsky Performance Status ≤ 30% (weight = 4; OR = 3.28; 95% CI = [1.80; 6.01], p < .001), leucocytes > 15 G/L (weight = 3; OR = 2.49; 95% CI = [1.18; 5.25], p = .017), pre-albumin ≤ 0.05 (weight = 3; OR = 2.42; 95% CI = [1.16; 5.04], p = .019) and male gender (weight = 2; OR = 2.25; 95% CI = [1.28; 3.97], p = .005). On the validation set (166 pts), a risk-index score ≥ 7 identified high risk pts, with a sensitivity of 70 %, specificity of 62 % and a positive predictive value of 78 %. Conclusions: This score could help “go/no go” decisions of chemotherapy in advanced cancer patients and reduces errors of life expectancy prediction from 80% to 22%.

No significant financial relationships to disclose.
Anticoagulation in cancer patients in hospice
Authors: Holmes H. M. , Bain K. T. , Luo R. , Zalpour A. , Bruera E. , Goodwin J. S.
Published: August 2020

e20509

Background: Low-molecular weight heparin (LMWH) is preferred over warfarin in patients with thromboembolic disease and active cancer, but no guidelines exist in hospice. Although warfarin may be less safe in hospice patients, hospices may prefer to provide warfarin due to lower cost and less invasiveness compared to LMWHs. We sought to identify disparities in the use of warfarin vs. LMWHs in cancer patients enrolled in hospice. Methods: We analyzed a dataset from a national pharmacy provider for more than 800 hospices. We identified patients with a terminal diagnosis of cancer who were enrolled and died in hospice in 2006 and who were prescribed warfarin or LMWH. Patient characteristics included age, gender, race, cancer diagnosis, length of hospice service, and number of comorbidities. For descriptive comparisons, the Kruskal-Wallis test was used for continuous variables, and the Chi-square test was used for categorical variables. Results: Of 54,764 patients with cancer admitted and deceased in 2006, 3874 (7.1%) were prescribed warfarin, and 1137 (2.1%) were prescribed LMWH. Patients prescribed warfarin (n=576) or enoxaparin (n=5) for treatment of atrial arrhythmias were excluded. The mean age was 70.6 years for warfarin and 64.8 years for LMWH (p<0.0001). The mean and median lengths of service, respectively, were 43.6 days and 23.0 days for warfarin and 35.0 and 18.0 days for LMWH, (p<0.0001). There were no differences for gender, and a higher proportion of white patients were prescribed warfarin. Patients prescribed warfarin had an average of 2.1 comorbid conditions, versus 1.6 conditions for LMWH (p<0.0001). Cancer diagnoses were significantly different between the two groups, with a higher proportion of patients with lung and prostate cancer taking warfarin. Conclusions: Patients prescribed warfarin were older, had more comorbidities, and a longer length of service than patients prescribed LMWHs. Further research is needed to determine the impact of anticoagulation on outcomes, especially cost and quality of life, for cancer patients in hospice. This study raises the need to establish guidelines for the appropriateness of anticoagulation in hospice patients with cancer.

No significant financial relationships to disclose.
Phase III randomized, placebo-controlled trial of L-carnitine supplementation for fatigue in patients with cancer
Authors: Cruciani R. A. , Zhang J. , Manola J. B. , Cella D. , Ansari B. , Fisch M. J.
Published: August 2020

e20532

Background: Carnitine deficiency has been reported in pts with cancer. This study was done to determine the prevalence of carnitine deficiency and the impact of supplementation on fatigue. Methods: Between November 2005 and January 2007, 376 pts with an invasive malignancy and normal hemoglobin levels with fatigue assessed as moderate or severe (score of 2 or higher on “I feel fatigued” question on FACIT-F) within 4 wks were randomized to 4 wks of supplementation with oral carnitine (n=189) or placebo (n=187) 1000 mg twice daily with meals. All pts then received 4 wks of open-label carnitine. Pts were stratified on gender, performance status (PS), and current receipt of chemotherapy. Quality of life was assessed at baseline, wk 4, and wk 8. The study was designed to detect a difference of 0.5 standard deviations in the change of average daily fatigue between the arms at 4 wks using the Brief Fatigue Index (BFI). Results: More than half of pts were male, had metastatic disease and were currently receiving chemotherapy. At study entry, 15% had ECOG PS 2–3, 39% were taking analgesics and 28% were taking antidepressants. There was no difference in the change in scores from baseline to wk 4 on the BFI, FACIT-F, Brief Pain Index (BPI) severity, BPI interference, or CES-D between arms (Wilcoxon p=0.56, 0.62, 0.61, .64, 0.93, respectively). The proportion of pts with severe fatigue or significant depression declined over time on both arms. Carnitine deficiency was defined using the acyl:free carnitine ratio and free carnitine levels. Deficiency levels were 34%, 11%, and 14% among pts randomized to carnitine and 32%, 33%, and 11% among pts randomized to placebo at baseline, wk 4, and wk 8, respectively (p<0.001 at 4 wks). An exploratory analysis suggests an improvement among pts who were carnitine deficient at the beginning of supplementation. Conclusions: Carnitine supplementation reduced deficiency levels but did not have a significant effect on fatigue, pain or depression. Analyses of carnitine metabolites are ongoing.

No significant financial relationships to disclose.
Understanding how out-of-pocket expenses, treatment value, and patient characteristics influence treatment choices
Authors: Wong Y. , Hamilton O. , Egleston B. , Salador K. , Murphy C. , Meropol N. J.
Published: August 2020

e20543

Background: Cost-sharing is a method to control “over-use” of healthcare services but may have the unintended consequence of reducing utilization of necessary services among vulnerable patients (pts). It is not known if cost influences pts’ choices of cancer treatments. Methods: A survey was administered to a convenience sample of pts on surveillance for localized cancer. Domains included demographic questions as well as clinical scenarios to elicit the maximum co-payment pts would be willing to pay for hypothetical cancer treatments. Scenario A described adjuvant therapy; questions varied reductions in recurrence rates from 5–20%. Scenario B described palliative therapy; questions varied 2-year survival between 19–34%. Scenario C described palliative therapy; questions varied improvement in median life expectancy from 11–20 months. GEE fit multiple logistic regressions examined pts’ characteristics associated with willingness to pay (WTP). Pts chose from 9 co-payment levels (highest: >$7,000/6 months for Scenario A; >$1,000/3 weeks for Scenarios B-C), which were dichotomized (highest 5 vs lowest 4 levels). Results: 60 pts completed the survey. Demographics: Female (78%); < 65 (83%), Caucasian (97%), college degree (58%). 13% reported making financial sacrifices to pay for treatment. Overall, pts showed a greater WTP for more effective treatments (p<0.05 for all 3 scenarios). In Scenario B, pts who were currently working demonstrated a greater WTP (OR 12.6 95% CI 2.0 -80.4) when controlling for dichotomized efficacy. In Scenario C, pts with a college degree showed greater WTP (OR 5.0, 96% CI 1.2–20.9). In addition, pts who reported having to make previous financial sacrifices for care showed lower WTP (OR 0.2 95%CI 0.04–0.6). Conclusions: Pts may assign a higher value to treatments of greater efficacy. Even among this relatively young, affluent and educated group, demographic variables were associated with WTP. Larger studies in more diverse populations are required to further elucidate how cost may influence pts'treatment choices and contribute to health disparities. These findings may inform health policy by suggesting benefit plans that use cost sharing to optimize use of limited health care resources without compromising access to needed care.

[Table: see text]
Endometrial cancer patients’ assessment of the benefits of exercise
Authors: Gil K. M. , Basen-Engquist K. , Lukowski J. , Detterman D. , Hopkins M. P. , Jenison E. L.
Published: August 2020

e20553

Background: Endometrial cancer patients remain at risk for other obesity related cancers and illnesses. Patients should be counseled to increase their physical activity, however, their belief concerning potential outcomes of exercise will affect how they are counseled. Methods: Patients treated for Stage I endometrial cancer with no other cancer diagnoses were asked if they had been exercising regularly for more than 6 months using the CDC definition of exercise (exercisers), how likely they thought regular exercise would result in health related outcomes (see Table ) and how important these outcomes are to them using Likert-like scales ranging from 1 to 5. A weighed calculation of how likely regular exercise would result in an outcome of importance to them was obtained by multiplying the two scores. Chi-square and t-tests were used to analyze data with SPSS V15. Results: 76 of 90 women approached completed the questionnaire (84%), mean age was 59.5 ± 1.1 (SEM). 45% were exercisers, their mean BMI was lower (31.2 ± 1.2 vs. 38.0 ± 1.4, p=0.001) and a non significantly lower proportion reported having diabetes (15% vs 26%) or hypertension (26% vs 43%). The majority of all women believed regular exercise would result in positive outcomes; a lower proportion of exercisers reported it very to extremely likely that regular exercise would reduce the risk of developing cancer (27% vs 54%, p=0.023) or osteoporosis (46% vs 73%, p=0.019). The majority reported these outcomes were very to extremely important to them; a lower proportion of exercisers reported reducing the risk of developing a new cancer or diabetes were (cancer 79% vs 98%, p=0.013; diabetes 78% vs 100%, p=0.003). Both groups believed feeling better physically and emotionally were important and likely consequences of exercise; exercisers were less likely to believe several other outcomes were important and likely consequences ( Table ). Conclusions: Women who exercise regularly and develop cancer may become disillusioned with the potential health benefits of exercise despite having improved health.

[Table: see text]

No significant financial relationships to disclose.
Pharmacokinetic and local tolerability profiles of three potential fentanyl nasal spray formulations developed for breakthrough cancer pain compared with oral transmucosal fentanyl citrate
Authors: Taylor D. R. , Fisher A. N. , Smith A. , Watling M. , Knight A. , Gabrail N. Y.
Published: August 2020

e20554

Background: The nasal route offers the ability to enhance fentanyl delivery and better match the rapid onset and short duration (30–60 min) of breakthrough cancer pain compared with standard oral delivery. However, conventional nasal fentanyl solutions can be associated with variable, and sometimes supratherapeutic maximum plasma concentrations (Cmax). To optimise rapid absorption and delivery, three novel nasal spray formulations have been developed: fentanyl pectin nasal spray (FPNS), fentanyl chitosan nasal spray (FChNS), and fentanyl in chitosan-poloxamer 188 solute (FChP). Methods: This phase I, open-label, crossover study was conducted in 18 healthy adult volunteers to compare the pharmacokinetic profiles of the three new nasal fentanyl formulations with oral transmucosal fentanyl citrate (OTFC). Subjects were dosed on four occasions, separated by a >3-day washout period, under naltrexone blockade, with the nasal sprays (each containing fentanyl citrate 100μg in 100μL) and OTFC 200μg according to a randomized sequence. Venous plasma fentanyl concentrations were measured before and up to 24 hours post-dose. Local nasal tolerability was assessed by a clinician and a reactogenicity questionnaire. Results: Compared with OTFC, mean AUCs∞ for all three nasal sprays were significantly higher (P<0.05) and bioavailability significantly greater (FPNS 132%; FChNS 154%, FChP 122%). Median tmax (FPNS 19.8min; FChNS 10.2min, FChP 15.6min) were significantly (P<0.001) reduced (OTFC 90min) and mean Cmax significantly increased with all nasal sprays compared with OTFC. Of the three nasal sprays, FPNS had the lowest nasal reactogenicity symptom incidence. Conclusions: Compared with OTFC, all three fentanyl nasal spray formulations demonstrated enhanced pharmacokinetic profiles appropriate for breakthrough cancer pain as evidenced by significantly increased systemic exposure and reduced times to peak plasma values. FPNS exhibited the most favourable tolerability profile.

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Validation of the Mexican-Spanish version of the EORTC QLQ-C15-PAL questionnaire for the evaluation of health-related quality of life in patients on palliative care
Authors: Onate-Ocana L. F. , Suárez-del-Real Y. , Allende-Pérez S. , Alférez-Mancera A. , Rodríguez R. B. , Jiménez- Toxtle S. , Gasca-Castro M. , Mohar-Betancourt A.
Published: August 2020

e20557

Background: Health-related quality of life (HRQL) is a fundamental outcome in oncology and this is particularly important in the palliative care setting. Our aim was to validate the Mexican-Spanish version of the EORTC QLQ-C15-PAL questionnaire, which is a brief version of QLQ-C30, for the measure of HRQL in terminal patients with cancer. Methods: Patients attending the Palliative Care Unit at the Hospital from July to October 2008 with terminal cancer, diagnosed by biopsy and without any active anti-neoplasic treatment were included in this study. Mexican-Spanish version of the EORTC QLQ-C15-PAL questionnaire was used to measure HRQL. Linear transformation of scale scores were done after EORTC guidelines. Correlation analysis was done obtaining the Spearman correlation coefficient and the Cochran alpha. Association of clinical parameters and scale scores were analyzed using one-way ANOVA and Chi-squared test. Test-retest comparison was tested using ANOVA for repeated measurements. Survival analysis was performed using the Kaplan-Meier and Cox's methods. Results: Eighty-three patients were enrolled in this study (mean age of 61.2 years). Compliance rates were high; all patients answered the questionnaire in less than 20 minutes and it was well-accepted. Five missing values in five different items were found. Scales in the QLQ-C15 distinguished between other clinically distinct groups of patients. Multi-trait scaling analysis demonstrated good convergent and discriminant validity. Cronbach's alpha coefficients were >0.7 in three of four multi-item scales. Test-retest scores were obtained from 25 patients and scores were consistent. Emotional function, Dyspnea, Insomnia and Appetite scales demonstrated an important association with overall survival by multivariate analysis (p<0.05). Conclusions: The Mexican-Spanish version of EORTC QLQ-C15-PAL questionnaire is reliable and valid for HRQL measurement in terminal patients with cancer, and appropriate for its use in clinical trials in Mexican patients.

No significant financial relationships to disclose.
Costs and outcomes associated with febrile neutropenia-related hospitalizations across patients with varying cancer types: A retrospective analysis
Authors: Schilling M. B. , Parks C. , Deeter R. G.
Published: August 2020

e20560

Background: Neutropenia, the major dose-limiting toxicity of chemotherapy, is a frequent, often serious, and sometimes fatal complication of myelosuppressive chemotherapy. Its economic and clinical impact is often under-appreciated, and thus this study evaluates the contribution of febrile neutropenia (FN) by tumor type as related to healthcare cost and mortality. Methods: FN patients in this study were identified as having cancer (ICD-9-CM: 140.xx - 208.xx), neutropenia (288.0x) and either opportunistic infections (110 total codes) or fever of unknown origin (780.6) who were hospitalized between 1/05 and 6/08 in a retrospective cohort study from the Aspen US healthcare database (∼11 million pts, >342 inpatient facilities, and >300 million charge-detail records). Unadjusted mean healthcare cost of hospitalization, length of hospital stay (LOS), and mortality rates were calculated, stratifying by cancer type (breast, metastatic breast, and lung cancers, non-Hodgkin lymphoma (NHL), or other hematologic tumors). Results: Among 598 hospitalized patients (mean age 63 years; 53% female) with cancer experiencing FN, the mean cost of hospitalization, LOS and mortality varied significantly by tumor type ( Table ). Conclusions: FN hospitalizations are costly and may be associated with significant mortality. Considerable variations exist across cancer types for hospitalization costs, LOS and mortality. The tumor type is important in assessing the economic and clinical impact of FN hospitalizations.

[Table: see text]

[Table: see text]
Vitamin D levels during and after high-dose vitamin D supplementation in women with early-stage breast cancer
Authors: Khan Q. J. , Kimler B. F. , Sharma P. , Reddy P. S. , Baxa S. , Klemp J. R. , Fabian C. J.
Published: August 2020

e20561

Background: Experts define vitamin D deficiency as a 25-hydroxyvitamin D (25OHD) level of < 20 ng/ml; a level < 32 ng/ml is considered insufficient for bone health and > 40 ng/ml may be associated with optimum musculoskeletal function and reduced risk for breast cancer. We conducted a study to determine the effect of high dose vitamin D3 at 50,000 IU/wk (HD vitD) on musculoskeletal symptoms from adjuvant letrozole in breast cancer patients. We present here the effectiveness of HD vitD in achieving optimum 25OHD levels and the rate of decline of 25OHD levels after 12 weeks of HD vitD. Methods: The cohort included post-menopausal women with early stage hormone receptor positive breast cancer initiating letrozole treatment. Women with baseline 25OHD levels < 40 ng/ml received 12 weeks of HD vitD. 25OHD levels were assessed at 6 and 12 weeks during HD vitD supplementation and at 3 and 6 months after completing HD vitD but while taking maintenance dose of 600–1000 IU of vitamin D3 daily. Results: 40 women that received HD vitD completed the follow-up phase of the study and are included in this analysis. At entry on study, median 25OHD level was 23 ng/ml; 38% of the women had vitD deficiency, 75% had insufficiency, and 93% had 25OHD levels < 40 ng/ml. Six weeks of HD vitD increased median 25OHD level to 60 ng/ml and another 6 weeks increased it further to 66 ng/ml. With only 6 weeks of HD vitD supplementation, 98% of the women achieved a 25OHD level of > 40 ng/ml. Median 25OHD levels 3 and 6 months after completion of HD vitD were 49 and 40 ng/ml, respectively. The median rate of decrease in vitD levels per month was 6.8% of the level at completion of supplementation. Using linear regression analysis, projected changes in 25OHD levels were calculated for each subject. Median extrapolated time to drop to a 25OHD level of < 40 ng/ml was 6.0 months, to <32 ng/ml was 7.8 months, and to <20 ng /ml was 10.6 months. Conclusions: Supplementation with vitD3 at 50,000 IU/week for 6 weeks is sufficient to achieve a 25OHD level of >40 ng/ml in 98% of postmenopausal women with breast cancer on an AI. After 12 weeks of HD vitD, there is a steady decline in 25OHD levels at a rate of about 7% per month despite continuing on 600 to 1000 IU of D3 daily. Thus, standard doses of D3 are not adequate to maintain 25OHD levels achieved by HD vitD.

No significant financial relationships to disclose.
The effects of surgery type on pretreatment distress and negative expectations in women scheduled for gynecologic surgery
Authors: Higgins S. C. , Schnur J. B. , Montgomery G. H. , Zakashansky K. , Bovbjerg D. H. , Dottino P.
Published: August 2020

e20562

Background: Most women with gynecologic cancer must undergo surgery as part of their treatment. Research suggests that laparoscopic surgery may lead to fewer side effects and faster recovery than laparotomy. Clinically, however, it is unclear if these benefits have led to decreased levels of emotional distress in patients prior to the procedure and/or to reduced expectations of negative side effects. The purpose of the present study was to assess and compare levels of emotional distress and expectations for postoperative discomfort and pain in women scheduled for either laparoscopic gynecological procedures, or laparotomy. Methods: Fifty-nine women scheduled for gynecologic surgery (mean age = 52.0 years) were recruited to this study. The dependent variables, pretreatment emotional distress and expectations of postoperative pain and discomfort, were assessed in the clinic with a numeric rating scales (0–10) prior to surgery. The independent variable, surgery type, was categorized into: minor laparoscopic, major laparoscopic, and laparotomy. Results: Univariate analyses revealed that mean distress levels between minor laparoscopic (x = 3.4), major laparoscopic (x = 4.2) and laparotomy (x = 3.8) did not differ (p>.1), nor did expectations of pain or discomfort (p's>.1). Demographic variables (age, race, education, marital status) did not show bivariate relationships with pre-surgical distress or expectations and therefore were not controlled for in the models. Conclusions: Based on the present results, the benefits of laparoscopic gynecologic surgery do not appear to affect patients’ levels of pretreatment distress or expectations of negative outcomes. The results suggest that women undergoing even minor gynecologic surgery may benefit from interventions to reduce preoperative distress, which has been shown to be a risk factor for increased postoperative side effects.

No significant financial relationships to disclose.