bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I trial of bortezomib in adults with recurrent malignant glioma
Authors: Phuphanich S. , Supko J. , Carson K. A. , Grossman S. A. , Nabors L. B. , Mikkelsen T. , Lesser G. , Rosenfeld M. , Desideri S. , Olson J. 
Published: March 2020

1567 Background: Bortezomib is a selective inhibitor of the proteasome that has been approved for the treatment of multiple myeloma and has also shown promising evidence of clinical activity against solid tumors. This study was undertaken to determine the maximum tolerated dose (MTD), toxicity profile, and biologic activity of bortezomib for the treatment of recurrent malignant glioma (MG). Methods: Eligible patients (pts) had supratentorial progressive MG upon radiotherapy and ≤ 1 prior regimen of chemotherapy. Dose escalation was conducted separately for pts taking enzyme inducing antiseizure drugs (EIASD+) and for those not (EIASD-). Bortezomib was given by bolus iv injection on weeks 1 and 2 of each 3 week cycle of therapy. The starting dose in both groups was 0.9 mg/m2. Cohorts of at least 3 patients were evaluated at each dose level. 20S proteasome activity was determined in whole blood lysates before and at 1 and 24 h after the first dose. Results: Fifty-nine evaluable pts (41 male/18 female) with a median age of 51 years and median KPS of 90% have been enrolled. All but 2 pts had received 1 prior chemotherapy regimen. In the EIASD- group, the weekly dose was escalated from 0.9 to 1.9 mg/m2 through 3 intermediate dose levels, with 1.7 mg/m2 established as the MTD. DLT experienced by 2 of 6 pts in the 1.90 mg/m2 dose level were grade 3 thrombocytopenia and grade 3 fatigue plus neurosensory toxicities. In the EIASD+ group, the dose has been escalated to 2.3 mg/m2 without the occurrence of any DLT. Ten additional EIASD- pts were treated at 1.7 mg/m2, with the most common adverse events being thrombocytopenia and peripheral neuropathy. The extent of proteasome inhibition in whole blood increased in a dose-dependent manner in both treatment groups. Mean proteasome inhibition in EIASD+ pts 1 h after receiving 2.1 mg/m2 of bortezomib (77 ± 12%) was similar to the 1.7 mg/m2 dose in EIASD- pts (79 ± 6%). Conclusions: The MTD for the weekly x 2 schedule of bortezomib in EIASD- patients, 1.7 mg/m2, is higher than the approved dose of 1.3 mg/m2 for the treatment of multiple myeloma. The enhanced tolerability of the drug when given together with EIASDs, for which the MTD is at least 2.1 mg/m2, is consistent with the diminished inhibition of 20S proteasome activity in these pts. No significant financial relationships to disclose.
Multiparametric magnetic resonance imaging (MRI) of diffuse intrinsic pontine gliomas (DIPG) after radiation therapy (XRT)
Authors: Warren K. E. , Draper D. , Butman J. A. 
Published: March 2020

1579 Background: The diagnosis and treatment of DIPG are based on typical MRI findings because of the inherent risk of biopsy. The standard treatment for this tumor is XRT. The limited ability of standard MRI to distinguish tumor from treatment effect hampers the determination of tumor response and time to progression. The objective of this study is to measure biochemical and physiologic MRI markers in DIPG after XRT that may aid in assessment of response. Methods: Fifteen pediatric patients (5 y, range, 1.8–12) with DIPG involving >50% of the pons and treated with XRT only were evaluated 12–64 days (median 38) following XRT (50.4–67.2 Gy, median 54 Gy) by MRI at 1.5 T. Standard T1, T2, and FLAIR MRI was performed in all cases. In addition, proton MR spectroscopy (MRS) was performed in 10 cases, MRS imaging (1H-MRSI) in 12, dynamic contrast enhanced MRI (DCE-MRI) in 14, and dynamic susceptibility weighted MRI (DSC-MRI) in 9. Ktrans and rCBV were measured using ROIs on enhancing portions of the tumor from the DCE- and DSC-MRI data after kinetic modeling. Results: Tumor area changed following XRT by a median of −29% (range, −61 to +37; SD, 33) and −17% (range, −65 to +101; SD, 45) on T2 and FLAIR, respectively. Enhancement was identified in 15 of 15 patients following XRT, and in only 6 of 15 prior to XRT (P = 0.0039 McNemar’s test). Following XRT, Choline: N-Acetyl Aspartate (CHO:NAA) ratio was 3.2 ± 1.9 by single voxel MRS, and the “worst voxel” CHO:NAA ratio was 3.5 ± 1.5 by 1H-MRSI. Overall, rCBV (1.98 ± 1.30) was elevated relative to normal cerebellum. However in 4 of these cases, rCBV was markedly elevated (>2), 4 were normal (1.0–1.3), and one was markedly reduced (0.6).Similarly, disruption of the blood-tumor barrier was variable across the group. Ktrans, a measure of permeability, ranged from 0.000 to 0.026 s−1, averaging 0.0086 ± 0.0085 s−1. Conclusions: Although all patients had a structurally similar tumor on MRI prior to XRT, significant variability in physiologic and metabolic response to XRT as measured by multiparametric MRI are noted. Presumably this variability represents real biologic differences resulting from differential responses to therapy. Determination of the prognostic significance is ongoing. No significant financial relationships to disclose.
Demonstration of an expedited breast care (EBC) clinic
Authors: Lopez A. , Venker C. C. , Howerter A. , Barker G. P. , Bhattacharyya A. , Scott K. M. , Descour M. R. , Richter L. C. , Krupinski E. A. , Weinstein R. S. 
Published: March 2020

16023 Background: Women report waiting for a breast biopsy result as a time of psychological distress. Waiting also delays entry into definitive oncology care, and patients in underserved communities may be lost to follow up. In this proof-of-concept demonstration, an Expedited Breast Care (EBC) clinic was developed to give patients the opportunity to receive same-day biopsy results. Methods: Patients requiring core breast biopsy at a community hospital were approached sequentially to participate. Following surgical biopsy, tissue underwent ultra-rapid fixation and processing. After paraffin sections were prepared and stained, the glass histopathology slides were imaged with a virtual slide scanner. Digital images were stored on a server and viewed on the Internet by a telepathologist at a tertiary care center. Light microscopy review was concurrently performed as the gold standard. After telepathology review and light microscopy confirmation, patients presented to the telemedicine suite to receive biopsy results. A teleoncologist at the tertiary care center presented all pathology results to the patient, whether benign or malignant. Time and patient satisfaction data were collected. Results: Nine patients have participated. Within 2 hours from the time the tissue arrived at the laboratory, digital images were available to the telepathologist. The teleoncologist presented results to patients within 3–5 hours after the biopsy procedure. Patients reported satisfaction with the same-day service, and stated they would seek EBC again in the event of a future breast biopsy. Many patients expressed relief at receiving results so promptly and felt they had avoided the stress of waiting longer for results. The elapsed time from mammogram to definitive oncology care was shorter for EBC patients compared to a control group of patients at a clinic not offering EBC, although the results did not reach statistical significance (Mann-Whitney U: Z = −1.804, p = 0.0713). Conclusions: These data indicate EBC can be successfully accomplished. Current studies to assess EBC’s role in facilitating prompt entry into definitive oncology care are underway. By incorporating rapid tissue processing with telepathology and teleoncology, EBC can improve access to breast care in underserved areas. [Table: see text]
Status of geriatric oncology in India: A national multicentric survey of oncology professionals
Authors: Arora B. , Parikh P. M. , Nair R. , Vora A. , Gupta S. , Sastry P. , Menon H. , Bakshi A. , Kumar P. , Goyal L. 
Published: March 2020

16035 Background: Elderly cancer patients are underrepresented in cancer services utilization and clinical research in India. National data on providers’ knowledge, attitude and practices with regard to elderly cancer patients is sparse and is urgently required to address needs of this vulnerable and growing population. Methods: A self administered questionnaire was mailed to nationally representative sample of practicing oncologists all over India. 112 Oncologists (Medical Oncologists-51%; Radiation Oncologists-25%; Surgical Oncologists-20%; allied fields-4%) responded out of 250 mailed Questionnaires. Results: A designated Geriatric Oncology unit is in existence in very few (<5%) centers. Majority (51%) considered patients with chronological age of >60 years as elderly for India. Although 75% of elderly patients receive some therapy, only 50% of potentially curable patients and a similar percentage of potentially incurable patients receive standard of care. Also, 50% patients require modification in their treatment and only two-third of treated patients complete therapy. The existent barriers to treatment included poor performance status (53%), advanced stage (16%), and co-morbidities (15%). Only 51% Oncologists always discussed and 28% always enrolled elderly patients in clinical trials. Standard of care and evidence based recommendations for elderly patients were felt to be lacking by 49% and 92% of respondents respectively. The need of separate trials for elderly and a separate discipline of Geriatric Oncology was voiced by 93% and 89% of respondents respectively. Major differences in treatment practice between medical oncologists and non medical oncologists are shown in table . Conclusions: Treatment practices and accrual of elderly cancer patients in clinical trials in India is far from optimal. Formation of a National Geriatric Oncology society and creation of designated Geriatric oncology services at key centers may enhance the understanding and clinical care of this population. [Table: see text] No significant financial relationships to disclose.
A humanized unconjugated antibody targeting CD33 (SGN-33; huM195) is active in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS)
Authors: Raza A. , Galili N. , Jurcic J. G. , Roboz G. J. , Wood B. L. , Grove L. E. , Drachman J. G. 
Published: March 2020

16500 Background: CD33 is a sialoglycan protein expressed on normal myeloid and monocytic cells as well as the vast majority of myeloid malignancies. A humanized antibody has been developed that recognizes CD33 and induces antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. In prior clinical testing, this antibody led to significant reductions in blasts in patients with relapsed and refractory AML. Methods: A phase I single-arm dose escalation trial was initiated at multiple sites to assess the safety, immunogenicity, pharmacokinetics, and activity of SGN-33 at higher doses than previously tested. Cohorts of 3–6 patients with advanced MDS or AML will receive intravenous SGN-33 at weekly doses of 1.5 to 8 mg/kg over 5 weeks. Clinical response will be determined by bone marrow morphology and hematologic improvement. Responding patients will be eligible for 4 additional infusions. Results: Treatment of 6 patients at 1.5 mg/kg/wk has been well-tolerated, with no dose-limiting toxicity or related adverse events > grade 2. The median age is 79.5 years (range 52–88), and all patients were previously untreated. One patient discontinued treatment because of refractory thrombocytopenia, unrelated to SGN-33. CD33 saturation of the bone marrow blasts after 2 infusions ranged from 27% to 84% with an average of 55%. The mean change in bone marrow blasts by flow cytometry after 2 weeks was −9% (range −68% to +44%; N = 5), and the marrow monocytes changed by −39% (range −90% to +86%; N = 5). Two patients have completed re-staging after cycle 1. Blasts decreased from 29% to 12% in an 88 year-old woman with AML and from 11% to 9% in a 79 year-old man with RAEB. Conclusions: SGN-33 is well tolerated at 1.5 mg/kg/wk, and dose escalation is ongoing. Antitumor activity was seen in elderly patients with previously untreated AML and MDS. Incomplete saturation of the CD33 on bone marrow blasts suggests that higher doses may improve efficacy. SGN-33 holds promise for the treatment of patients with myeloid malignancy who are ineligible for aggressive therapy. [Table: see text]
University of Wisconsin experience treating adult ALL with the BFM regimen
Authors: Medlin S. C. , Kahl B. , Longo W. , Williams E. , Lionberger J. , Kim J. , Kim K. , Juckett M. 
Published: March 2020

16501 Background: Berlin-Frankfurt-Munster therapy (BFM) is an effective regimen for acute lymphoblastic leukemia (ALL) in children and young adults (Lancet 2:921–924,1988). Treating children and young adults at higher risk for relapse with an augmented BFM was shown to increase both event free and overall survival (NEJM 338:23,1663–1671,1998). Outcomes using standard BFM or augmented BFM in adults are unknown. Methods: This is a case-series of 29 adult patients treated with the BFM regimen. Patients were stratified into low, intermediate and high-risk groups based upon the following characteristics: age, white blood cell count, adverse cytogenetics and absence of CD 10. Low risk patients received the standard BFM regimen. Intermediate risk patients were given augmented BFM if less than 50 years old, standard BFM if older than age 50. High-risk patients received augmented BFM. Cranial irradiation was omitted in most patients (25/29). Events were defined as relapse, death from any cause, and stopping treatment for any reason. Results: Fifteen patients (median age 38, range 19–70) were treated with standard BFM and 14 patients (median age 37, range 21–72) with augmented BFM. Complete remission at day 28 was 93% (27/29). For the entire group, the 3-year overall survival was 60% with a 3-year event free survival of 45%. Patients treated with augmented BFM experienced a 3-year EFS, PFS, OS of 26%, 43%, and 48% respectively. Patients treated with standard BFM had a 3-year EFS, PFS, OS of 60%, 78%, and 78% respectively. Toxicity was common with significant neuropathy and neutropenic fever occurring in 83% and 48% respectively. Septic shock occurred in 17% of patients. Severe toxicity resulted in 1 death and discontinuation of BFM in 3 patients. The entire regimen was completed in 33 % of those treated with augmented BFM and 71% of those treated with standard BFM. Conclusion: Standard BFM is an effective and tolerable regimen for treatment of adult ALL. Augmented BFM is a difficult regimen for adult patients to complete. For both regimens, the 3-year PFS and OS compare favorably to other published regimens. No significant financial relationships to disclose.
Alemtuzumab (ALZ) as treatment for severe paraneoplastic pemphigus (PNP) associated to B-cell chronic lymphocytic leukemia (CLL)
Authors: Nielsen R. B. , Steinicke T. , Peterslund N. A. , Hohwy T. , Bang K. , D′amore F. 
Published: March 2020

16520 Background: ALZ is a monoclonal antibody used in the treatment of CLL. PNP is a mucocutaneous disease frequently associated with B-cell malignancies. PNP is often refractory to immunosuppressive drugs and is frequently fatal. Methods: We here report two cases, where ALZ induced a complete and sustained remission of both PNP and CLL and one case with a significant remission of PNP alone. Results: A 68-year old male with a 4-year CLL history developed blisters and ulcers on the extremities and trunk and severe stomatitis. Despite steroids, fludarabine, cyclophosphamide, ciclosporin A, and azathioprin, PNP exacerbated. A standard 12-weeks ALZ schedule was initiated. PNP lesions gradually regressed under the last weeks of treatment and resolved completely a few weeks later. A bone marrow biopsy showed morphologic and flowcytometric signs of remission. Now, 30 months after ALZ, the patient’s PNP and CLL are still in remission. Almost a year after this first case, a 77-year old male with a 3-year CLL history, presented with severe mucocutaneous lesions of the lips, oro-esophageal cavity, penis and extremities. PNP was diagnosed and a standard 12-weeks ALZ schedule was initiated. The lesions began to regress during the last weeks of treatment and normalized within the subsequent 8 weeks. This remission had a duration of 1½ year, after which the patient was hospitalized with evidence of PNP relapse. He is currently undergoing renewed ALZ therapy. An 80-year old female with a 4-year history of CLL, showed signs of disease progression after 2 treatment-free years.She then developed mucocutaneous lesions diagnosed as PNP. In spite of cytoreductive treatment, both PNP and CLL progressed and ALZ was given. All PNP lesions promptly disappeared, but recurred already 2 weeks after discontinuation of ALZ. Concomitantly, the patient developed a Legionella pneumonia. In spite of erythromycin, she deteriorated clinically and died one month later. At autopsy, marked CLL involvement of bone marrow and retroperitoneal lymph nodes was found. Conclusion: ALZ is an effective treatment in severe CLL-associated PNP. The observed duration of response was variable. A larger number of patient observations is necessary in order to identify patterns of response. No significant financial relationships to disclose.
Skin reactions with imatinib in CML patients: An Indian experience
Authors: Attili S. V. , Anupama G. , Dadhich H. K. , Saini K. S. , Bapsy P. P. , Batra U. 
Published: March 2020

16522 Background: Skin reactions are observed in up to 30–45% of all patients of CML on imatinib therapy. Owing to its low molecular weight it is less likely to be immunologically mediated. Therefore most of them can be managed without discontinuation of therapy. We tried to look into the spectrum of the skin reactions observed in CML patients receiving imatinib, and tried to see any change with the phase of the disease (chronic/accelerated/blast crisis) or difference in the brand of drug they are receiving. Methods: This retrospective study was conducted at Kidwai Memorial Institute of Oncology, Bangalore, India. A total of 235 patients were analyzed between Jan 2004 and Dec 2005. Clinical details were noted from the case records. Differences were calculated for the means using SPSS 13.0 for windows. Results: The age, total episodes of reactions, mean time to develop and to heal along with grade of reactions are summarized in the table . A total of 191 patients received the international brand and the total episodes of skin reactions observed were 68 with 4 grade III/IV toxicities. 54 patients received local brand and 17 of them developed skin reactions and 2 of which were grade III/IV. There is no difference in the time taken for resolution of skin reactions (23.8 + 6.7 vs. 25.2 + 7.5) (p = NS). Conclusion: There are no significant differences in skin reactions observed with brand of imatinib used. Patients with accelerated phase and blast crisis developed reactions at little earlier. As most of the patients in the later said conditions had a shorter survival, we could not comment conclusively on the time to heal according to phase of the disease. [Table: see text] No significant financial relationships to disclose.
Efficacy and feasibility of intensive induction therapy in very elderly patients with acute myeloid leukaemia
Authors: Biaggi G. , Santagostino A. , Manachino D. , Posca T. , Forti G. , Salva S. , De Marino E. 
Published: March 2020

16528 Background: Intensive Induction Treatment (IIT) increases chances of longer survival in acute myeloid leukaemia (AML). Our aim was to improve outcome and to evaluate safety and tolerability of IIT in very elderly patients (pts). Otherwise they have a median surviving time of 11 weeks without treatment. Methods: From October 2003 to November 2005 we treated 23 pts, 16 Males (M) and 7 Female (F); median age 75.5 years (range 68–95). According FAB classification they were 1 M0, 10 M1, 5 M2, 6 M4, 1 M5. ECOG performance status (PS) was 0 in 6 pts, 1 in 5 pts, 2 in 7 pts and 3 in 5 pts. All pts underwent IIT with different schedules: only a female 95 years old had less intensive treatment. Immune-chemotherapy was also admitted. Schedules were: 3+7 IDA+ARA-C in 8 pts; MY-FLAI in 7 pts; VP+ARA-C 1 = ≥ 5 in 2 pts; IDA+ARA-C 1 = ≥ 2 in 4 pts; ARA-C + 6TG in 1 pt. Eleven pts underwent second line treatment. Results: Five pts are alive and 18 dead. We obtained 7 complete responses (CR) (32%) and 1 partial response (PR) (RR 36%);. The median CR duration was 7.5 months (range 1–12).Throughout IIT we observed 5 toxic deaths (23%) because of infections and 2 deaths not leukaemia therapy related (heart failure). The median Overall Survival (OS) was 9 months. Conclusions: Despite the toxic deaths due to the treatment, we obtained in 32% of the pts CR longer compared to palliative or best supportive care; also the median OS was longer than we can expected without chemotherapy. Our data support in our opinion the feasibility and the utility of an IIT in very elderly patients with good PS. No significant financial relationships to disclose.
Biodistribution of paclitaxel poliglumex (PPX) in lung: Analysis of gender-related alterations in a preclinical model
Authors: Allievi C. , Strepponi I. , Bastrup U. , Piazzoni L. , Tavazzi S. , Pisano R. , Pezzoni G. , Fornasier M. , Bernareggi A. , Singer J. W. 
Published: March 2020

17003 Background: PPX is a macromolecular drug conjugate that links paclitaxel with poly-L-glutamic acid; the release of paclitaxel is dependent on metabolism by lysosomal proteases, particularly cathepsin B. Cathepsin B is upregulated by estrogen in both reproductive and somatic tissues that express estrogen beta receptors, including normal lung epithelial cells. Cathepsin B mRNA is also increased by estrogen and decreased by anti-estrogens in the 201T NSCLC cell line (P. Hershberger, personal comm.). Clinical data from Phase III studies in NSCLC showed improved survival in women receiving PPX compared to women in the control-arm, particularly those that were pre-menopausal or with pretreatment estradiol levels >30 pg/ml. In contrast, men had similar survival regardless of treatment. Methods: To examine the effect of estrogen on PPX biodistribution and metabolism, male, sham-operated female, and oopherectemized (OPX) female adolescent rats were treated with [14C]PPX (25 mg paclitaxel eq/kg). Radioactivity, as well as total and unconjugated paclitaxel, were measured in plasma, liver, and lung weekly for 4 wks. Results: Plasma thalf values for radioactivity were appr. 3- and 1.5-fold higher in OPX females and intact females, respectively, compared to males; plasma AUCs were increased 1.8- and 1.5-fold, respectively. The lung AUC for radioactive PPX was similar for male and OPX females (11.8 and 15.1 hr*mgeq/g, respectively) but significantly higher for intact females (39.3 hr*mgeq/g). Total paclitaxel concentrations in the lung were 2-fold higher for females compared with either male or OPX rats (p < 0.05 at 1 wk, and p < 0.01 at 4 wks post dosing). No significant differences were observed in liver. Conclusions: OPX is associated with prolonged PPX plasma clearance compared to controls, and intact ovarian function is associated with enhanced distribution of PPX to lung tissue. These data provide the first evidence that ovarian function affects PPX pharmacokinetics and biodistribution; continued preclinical investigations will further characterize the mechanism for its apparent enhanced clinical efficacy in chemotherapy-naïve women with advanced NSCLC and intact ovarian function. [Table: see text]