bluuebunny/crossref_metadata_2025_split huggingface dataset:
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. [Table: see text]
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.