bluuebunny/crossref_metadata_2025_split huggingface dataset:
An IMRT technique to increase therapeutic ratio of breast irradiation in patients with early stage left breast cancer: Limiting second malignancies
Authors: Ahmed R. S. , Fiveash J. B. , Popple R. A. , Spencer S. A. , De Los Santos J. F. 
Published: March 2020

10791 Background: The clinical application of IMRT for adjuvant treatment of breast cancer has been the subject of increasing study in recent years. IMRT plans have improved target coverage and reduced dose inhomogeneities observed within the breast in standard plans. IMRT was able to reduce doses delivered to the heart, lungs, and right breast at clinically significant doses, but this has been at the cost of larger volumes of low dose radiation to these structures and thus, increasing the risk for second malignancy. Our goal was to develop an IMRT beam arrangement that did not result in additional low dose spill to risk organs while maintaining equal or better target coverage. Methods: Five patients with early stage left-sided breast cancer, who underwent breast conservation surgery, and adjuvant radiation using standard wedged tangential fields, were chosen for this comparative study. An IMRT plan consisting of 6 tangential beams (3 medial and 3 lateral) was generated by using the gantry, collimator and table angles of the standard plan used for the conventional radiation (CRT), and moving the table +10 and −10 degrees on each side. The prescription dose for both CRT and IMRT plans was 45 Gy, 1.8 Gy/fraction, prescribed to the isocenter which was placed near the center of the breast. Results: IMRT plans provided significantly better coverage of the left breast than CRT plans, (p=0.03). Although dose heterogeneity was greater with the IMRT plans, the difference was not significant (p = 0.68). The mean volumes of the heart, lung, and right breast were lower in patients planned with IMRT at all dose levels from 5% to 100% dose (5% increments). This difference was significant for volumes receiving 2.25 Gy for the heart (p = 0.003), volumes receiving 2.25 Gy, 4.5 Gy, 6.75 Gy, 33.75 Gy, 36 Gy, 38.25 Gy, and 42.75 Gy for the lung (p = 0.014, 0.04, 0.044, 0.05, 0.049, 0.045, 0.05, respectively). Surprisingly, breast IMRT resulted in significantly lower right breast volumes irradiated at all dose levels compared to CRT. Conclusions: A six-tangential field IMRT technique achieved significantly better left breast coverage while maintaining lower doses to risk organs at all dose levels and therefore, reducing the potential for induction of a second malignancy. No significant financial relationships to disclose.
Acute toxicity analysis of patients receiving surgery, Gliadel wafer implantation, and postoperative daily temozolomide with radiation therapy for primary high-grade glioma
Authors: Heery C. R. , Desjardins A. , Quinn J. A. , Rich J. N. , Gururangan S. , Vredenburgh J. J. , Friedman A. H. , Reardon D. A. , Friedman H. S. 
Published: March 2020

11504 Background: Treatment of patients with newly diagnosed malignant glioma using Gliadel wafer implantation at initial surgery has been shown to increase survival (Westphal et al 2003). Similarly, administration of temozolomide during and after radiotherapy has also been shown to increase survival in this patient population (Stupp et al 2005). Accordingly use of both Gliadel and temozolomide may be advantageous for these patients although it is possible that the toxicity of these two approaches used together might be prohibitive. Methods: The Preston Robert Tisch Brain Tumor Center at Duke has occasionally treated with this approach over the last several years, and we now present an analysis of the observed acute toxicity. We retrospectively reviewed the Duke patients treated with surgery plus Gliadel wafer placement followed by daily temozolomide (75 mg/m2-150 mg/m2) and radiation therapy. Results: Of 28 patients reviewed, four patients were diagnosed with AA (WHO grade III), two patients were diagnosed with AO (WHO grade III) and the remaining 22 patients were diagnosed with glioblastoma multiforme (WHO grade IV). Two of the 28 7.1%) patients experienced grade 3 or 4 hematologic toxicity during radiation and daily temozolomide therapy. This is similar to the 7% of patients found to have hematologic toxicity reported by Stupp et al (2005). Three patients (10.7%) had grade 3 or 4 seizure activity. Two patients (7.1%) had grade 4 pulmonary emboli. No events of cerebral edema or wound complications were noted in this review of patient events following Gliadel wafer placement. Conclusions: In summary, the addition of Gliadel wafer placement at the time of surgery followed by radiation therapy with concurrent daily low dose temozolomide does not appear to have significant acute toxicity over that observed with radiation therapy and daily temozolomide. Future formal trials combining these therapeutic strategies may allow evaluation of the possible survival advantage associated with this approach. [Table: see text]
Treatment with temozolomide for malignant gliomas: Is rechallenge with alternative dosing regimens successful?
Authors: Balmaceda C. , Pannullo S. , Serventi J. , Sisti M. , Bruce J. , McKhann G. , Lai R. , Rosenfeld S. , Fine R. 
Published: March 2020

11514 Background: Temozolomide (TMZ) is an alkylating agent with activity against malignant gliomas. A variety of dosing schedules has been used including: 5 days on/21 days off (200 mg/m2/d), bid dosing (initial bolus of 200 mg/m2 followed by bid dosing of 90 mg/m2 × 9 doses), and 7 days on/7 days off (150 mg/m2/d). It is not known which regimens are the most effective. Furthermore, it is not known whether patients failing one schedule will respond to alternative ones. Materials and Methods: We report on a retrospective series of 8 patients (7 M, 1 F), who were treated with TMZ at least twice. Mean age at recurrence was 48 (26–58). Pathology revealed GBM (3), AA (4), and AO (1). 7 patients had received prior XRT. 7 patients had a local (L) recurrence at the time of retreatment with TMZ, and one patient had leptomeningeal (LM) and L recurrence. 7 pts received TMZ alone both at the time of the first recurrence and at the time of rechallenge. One patient had received TMZ concommitant with XRT and TMZ alone at the time of rechallenge. Results: See Table . Toxicity was mild and not different than that seen in patients treated with the first course of TMZ. Conclusions: While the number of patients is limited, some observations can be made: 1) patients can respond to TMZ at rechallenge, particularly if a prior response to TMZ had been observed. 2) Some patients who fail or respond modestly to one regimen may achieve a better response to alternative dosing schedules. Further studies need to address whether one regimen of TMZ given at rechallenge allows an improved survival as compared with other regimens without sacrificing safety. [Table: see text] [Table: see text]
Combination of bevacizumab, a monoclonal antibody to vascular endothelial growth factor (VEGF), and temozolomide: Study of cases
Authors: Kirkpatrick J. , Desjardins A. , Vredenburgh J. J. , Quinn J. A. , Rich J. N. , Sathornsumetee S. , Gururangan S. , Friedman A. H. , Friedman H. S. , Reardon D. A. 
Published: March 2020

11522 Background: The prognosis for glioblastoma multiforme remains poor. Survival is generally limited to less than 1 year. Currently available standard treatments have not allowed, thus far, to prolong survival significantly. Response rates observed in clinical trials evaluating glioblastoma multiforme are usually less than 20%. Knowing that malignant gliomas have high concentrations of VEGF receptors, and the higher the VEGF receptor concentration, the worse the prognosis, we decided to evaluate the efficacy of bevacizumab in malignant brain tumor patients. Bevacizumab is a humanized IgG1 monoclonal antibody to VEGF, which is synergistic with chemotherapy for most malignancies. We performed a phase II study combining bevacizumab with irinotecan for patient with malignant gliomas and observed an unprecedented response rate of 63%. Methods: Building of those results, we decided to treat a number of our patients with voluminous unresectable disease with bevacizumab and temozolomide as an upfront regimen. Temozolomide is an oral methylating agent known effective for primary malignant brain tumor patients. A phase III trial, first presented at the ASCO meeting of 2003, demonstrated the efficacy of temozolomide for newly diagnosed glioblastoma multiforme patients, establishing temozolomide as the new standard of care. Given the known results with temozolomide as monotherapy and the combination of bevacizumab with irinotecan, we treated patients with temozolomide and bevacizumab upfront. Results: With this new combination, some patients demonstrated dramatic improvement clinically and radiographically. The combination has been well tolerated thus far, with no incidence of hemorrhage or arterial thrombosis observed. Conclusions: Results will be updated at the time of presentation. [Table: see text]
Phase I pharmacokinetic(PK)/food effect and safety study of satraplatin in patients (pts) with advanced solid tumors
Authors: George B. J. , Ricart A. D. , Calvo E. , Chu Q. , Sarantopoulos J. , Greene D. , Nathan F. E. , Petrone M. E. , Tolcher A. W. , Papadopoulos K. P. 
Published: March 2020

12014 Background: Satraplatin (S) is a novel oral platinum analog that has demonstrated preliminary activity in hormone refractory prostate cancer (HRPC). A large (950 pts) worldwide, randomized phase III trial evaluating S as 2nd line therapy for HRPC recently completed enrollment. The current study was designed to determine the PKs of S under fasted and fed conditions, as well as treatment efficacy and toxicity. Methods: S was administered orally at 80 mg/m2/day (d) on d1–5 q 35 days, with prophylactic antiemetics. For the 1st cycle, pts were randomized to receive d1 and d5 doses of S in either the fed or fasted state when PK sampling was performed. The fed/fasted state was reversed for the 2nd cycle. Subsequent doses of S were given in the fasted state. Results: 17 pts were enrolled (9M/8F), median age 62 (range 33–78) and tumor types: HRPC (7), breast (3), 1 each with anal, parotid, leiomyosarcoma, Merkel cell, ovarian, mesothelioma, and neuroendocrine tumor. The median no. of prior regimens was 3 (range 1–8). A total of 58 cycles of S were given. Grade 3–4 hematologic toxicities (1st 2 cycles) included: neutropenia (11%), thrombocytopenia (24%) and anemia (24%). The hematologic nadir occurred during week 4. There was no grade 3–4 nausea, vomiting or diarrhea. No significant cardiac, renal, hepatic, or neurologic toxicity was observed. The peak plasma concentration (Cmax) for platinum in plasma ultrafiltrate (PUF) was decreased by 20% when S was administered following a high fat meal compared to the fasting condition. There was no effect of food on AUC0–24 hr. The time of Cmax (Tmax) was delayed in the fed state. Table shows PK parameters. One PR (HRPC) and 4 SD ≥ 5 months (breast, ovarian, parotid and HRPC) were confirmed. Conclusions: There is an effect of food on the Cmax, however the clinical implications are unknown at this time. For this reason, it is recommended that S be administered to pts in the fasting state. At the dose of 80 mg/m2/day, S was well tolerated in this group of heavily pretreated patients. [Table: see text] [Table: see text]
Fixed dose rate (FDR) gemcitabine (G) and capecitabine (C) in patients with advanced and/or metastatic cancer: phase I trial
Authors: Santini D. , Vincenzi B. , Virzì V. , La Cesa A. , Schiavon G. , Leoni V. , Gasparro S. , Grilli C. , Calvieri A. , Tonini G. 
Published: March 2020

12016 Background: Combination of C and G has been demonstrated to be well tolerated, with apparent efficacy in patients with advanced cancers. To determine the toxicity of C plus Fixed Dose Rate (FDR) G in metastatic cancer patients, a phase I trial was conducted. Methods: This is an open-label, single-center, dose-escalating phase I study. C was administered orally according to the standard 21-day schedule: bid in equal doses (650 mg/m2 bid) for 14 days every 21 days. G was administered at a FDR of 10 mg/m2 per min in escalating durations of infusion on days 1 and 8 every 21 days. The doses of G explored were 600, 700, 800 mg/m2 infused at FDR in 60, 70 and 80 minutes, respectively. 15 pts (10 female, 5 male), aged 37–70 yr (median 66) with a variety of advanced solid tumors have been treated (11 peri-ampullary cancers, 3 colorectal cancers and 1 ovarian cancer). The FDR G dose was escalated when 3 patients in a cohort had completed two cycles of treatment without experiencing dose-limiting toxicities (DLT). The MTD was defined as the dose level at which no more than one of nine patients experienced a DLT. Results: No DLT occurred at doses of 600 and 700 mg/m2 in any of the 3 patients included at each level. At 800 mg/m2, 1 of 9 patients experienced DLT (neutropenia grade 4 with fever). The non-haematological toxicities have been generally mild or moderate in all patients (grade 2 stomatitis: 4 patients; grade 2 fatigue: 3 patients; grade 2 nausea/vomiting: 2 patients). 2 patients showed one episode of grade 4 neutropenia spontaneously regressed in 3 days. 2 patients showed one episode of grade 2 thrombocytopenia. The recommended dose for further studies is C bid in equal doses (650 mg/m2 bid) for 14 days (28 doses) plus FDR G at 800 mg/m2 infused in 80 minutes on days 1 and 8 every 21 days. Other patients with periampullary carcinoma are being evaluated at the same dose level, with an ongoing evaluation of cumulative (all cycles) toxicity and efficacy. In terms of response, we have observed 2 PR and 3 SD in the 6 pancreatic cancer patients evaluated for response after the first 3 cycles. Conclusions: C plus FDR G combination seems to be a feasible and safety approach which has demonstrated promising clinical activity. No significant financial relationships to disclose.
Phase I study of pegylated liposomal doxorubicin (PLD) and irinotecan (I) in patients with solid tumors
Authors: Pillot G. A. , Wildi J. , Tan B. , Suresh R. , Fracasso P. , Govindan R. 
Published: March 2020

12023 Background: Irinotecan (I) and doxorubicin are cytotoxic agents that interact with topoisomerase I and II respectively, and display some evidence of preclinical synergy. Pegylated liposomal doxorubicin (PLD) is a novel formulation of doxorubicin that may be more tolerable than doxorubicin. We sought to define the maximum tolerated dose (MTD) of PLD and I when given in combination. Methods: Patients (pts) with good performance status (PS 0–2) and adequate cardiac, renal, liver, and bone marrow function who had received any number of prior therapies for advanced solid tumors were eligible. Pts in the first cohort received PLD at a dose of 20 mg/m2 IV on day 1 and I 100 mg/m2 on days 1 and 8 of a 21 day cycle to a maximum of 6 cycles. Growth factor support was not permitted. Results: Eleven pts were enrolled, 6 male, 5 female. Median age of the pts was 63 years (range 19–73). There were 2 cases each of non-small cell lung cancer, renal cell carcinoma, and biliary carcinoma, and one case each of breast, pancreatic, ovarian, colon, and bladder carcinoma. Three pts were initially enrolled without dose-limiting toxicity (DLT) in cohort 1, and six pts were subsequently enrolled in cohort 2 (20 mg/m2 PLD and 125 mg/m2 I), with 2 patients experiencing DLT (neutropenia, diarrhea, and fatigue). Two additional pts have been enrolled in cohort 1 (5 pts total) without DLT, and the 6th patient will be enrolled soon to define the MTD. Grade 3 neutropenia was noted in 1 pt and grade 4 neutropenia in 2 pts. Other non-hematologic toxicities across all cycles have included grade 3 anorexia, diarrhea, nausea, and fatigue in 2 pts each, and 1 pt each with grade 3 dehydration, emesis, pneumonitis, and DVT. No cardiac toxicity has been observed. Of 6 evaluable pts, 4 experienced stable disease (1 each of NSCLC, breast, pancreas, and renal cell carcinoma). Conclusions: The combination of pegylated liposomal doxorubicin and irinotecan is feasible and well- tolerated. The maximal tolerated dose is likely to be PLD 20 mg/m2 d1 and I 100 mg/m2 d1 and 8 IV q 21 days (pending enrollment of the last patient). This study was supported by Tibotec Therapeutics, Division of Ortho Biotech. [Table: see text]
Isolation of large numbers of human mesenchymal stem cells from discarded filters after bone marrow harvests: Implications for therapy
Authors: Mageed A. S. , Pietryga D. , Gagin S. , West R. 
Published: March 2020

12501 Background: Bone Marrow (BM) is an excellent source of Mesenchymal Stem Cells (MSCs) which can be expanded and used clinically. There is a growing evidence that MSCs can promote engraftment and reduce Graft versus Host Disease (GVHD). Bone marrow harvests are passed through 850μ, 500μ and 200μ filters to trap bony spicules and clots before infusion into patients. We hypothesize that the filters would also trap a significant number of MSCs which can be useful clinically after isolation and possible expansion. Methods: Bone marrow collection kits were obtained after informed consent of the donor (n = 11). Specimens were obtained in the course of scheduled bone marrow harvests. Cells were isolated and cultured from each portion of the device. Results: An average of 1×109 total mononuclear cells was obtained from the discarded marrow collection devices. Cells isolated in this experiment conform to published data regarding MSCs. The immunophenotype was CD44+, CD73+, CD90+, CD105+, CD14−, CD34−, CD45−, HLA-DR−, negative for leukocyte lineage specific antigens and positive for Prolyl-4-Hydroxylase. The cells were morphologically consistent with published data, being bilaterally symmetrical and forming conspicuous fibroblastoid colonies which readily grew to confluence and followed differentiation pathways to both adipose osteoid tissue. Fresh cells from the kits may also contain a precursor for MSCs that is CD90− and CD73−. Sorting for this precursor population yielded colony forming units consistent with MSCs. Conclusion: This represents a novel strategy for obtaining “healthy” material for potential therapy and study. No significant financial relationships to disclose.
Mimotopes of the disialoganglioside GD2 elicit anti-GD2 antibodies recognising GD2 on melanoma cells
Authors: Brämswig K. H. , Riemer A. B. , Förster-Waldl E. , Pollak A. , Zielinski C. C. , Pehamberger H. , Lode H. N. , Scheiner O. , Jensen-Jarolim E. 
Published: March 2020

12505 Background: The disialoganglioside GD2, a carbohydrate antigen, is expressed on all tumors of neuroectodermal origin, including melanoma, sarcoma, neuroblastoma and small cell lung cancer. Due to its specific expression on tumor surfaces, GD2 is an attractive target for immunotherapy. The mouse/human chimeric antibody form ch14.18 was already applied in melanoma and neuroblastoma trials as passive immunotherapy. We aimed to replace the poorly immunogenic ganglioside with highly immunogenic peptides, in order to establish an active immunotherapy. Methods: We used the ch14.18 antibody to select GD2 mimotopes. In the present study, two mimics of the ch14.18 epitope were chosen for immunogenicity evaluation. The mimics were coupled to KLH (keyhole limpet hemocyanin) in order make them more immunogenic. Three groups of BALB/c mice were immunized i.p with the mimotope conjugates (GRL-KLH or DGG-KLH), or the carrier protein KLH alone. Results: BALB/c mice immunized with the mimotope conjugates indeed showed a specific humoral immune response towards the purified original antigen GD2 in ELISA, and also against the natural GD2 melanoma cell lysate in Western Blots. As the elicited antibodies were of the IgG isotype, the mimotope conjugates are capable of recruiting T cell help and inducing memory phenomena. Conclusion: We are able to show that an epitope of the carbohydrate antigen GD2 can successfully be translated into immunogenic peptide epitope mimics. Moreover, immunizations with these mimics induced IgG antibodies again recognizing the original antigen. We thus provide evidence that GD2 mimotopes are suitable candidates for active immunotherapy of GD2 expressing tumors. The work was supported by BioLife Science GmbH, Vienna, Austria; by project grant #10965 of the Austrian National Bank Science Fund; and by the Center of Excellence in Clinical and Experimental Oncology (CLEXO), Austrian Federal Ministry of Education, Science and Culture (GZ200.062/2-VI/1/2002). A.B. Riemer and K.H. Brämswig are recipients of Hans & Blanca Moser Fund scholarships. The work was also supported by DFG (Lo635–2) and Fördergesellschaft Kinderkrebs-Neuroblastomforschung to H.N.Lode. [Table: see text]
Yttrium-90 (90Y) ibritumomab tiuxetan for treatment of relapsed or refractory non-hodgkin’s lymphoma: The Western Pennsylvania Cancer Institute experience
Authors: Jasthy S. , Sudan N. , Haq B. , Lister J. 
Published: March 2020

12511 Background: Yttrium-90 (90Y) ibritumomab tiuxetan (Zevalin) radioimmunotherapy is an effective agent for treatment of CD20+ B-cell lymphoma (NHL).It is approved for treatment of relapsed or refractory, follicular or transformed B cell lymphoma. An overall response rate ranging from 74% to 82% has been reported. Median response duration of 11.5 to 28.1 months has been reported. Methods: We identified, retrospectively, 37 patients treated at our institution with relapsed or refractory NHL who were treated with 90Y ibritumomab tiuxetan at a dose of 0.3mCi/kg or 0.4mCi/kg. Response rate and survival were assessed. Median age was 60 years (range 28–82 years) of which 65% were male. Follicular lymphoma was present in 57% (n = 21) and diffuse large B-cell lymphoma in 22% (n = 8) of patients. Advanced disease (stage III or IV) was present in 84% (n = 31) of patients. All of the patients had received at least one prior regimen and 68% (n = 25) had received ≥ 3 regimens before 90Y ibritumomab tiuxetan. Results: Overall response rate was 65% (24/37); CR 43% (16/37); PR 19% (7/37); SD 3% (1/37). Duration of response was 13.3 months (range 4 to 48 months) with response duration greater than 12 months in 35% (n = 13) of the patients. Of responders, 67% (16/23) had failed to respond to prior immediate therapy. The only toxic event was pancytopenia, which predictably occurred after treatment. No patients died of toxicity and all toxicity was reversible. Conclusions: 90Y ibritumomab tiuxetan was well tolerated and effective for our patients.We document durable response in our patients with relapsed or refractory NHL and with advanced stage disease. Further study of ibritumomab tiuxetan using different doses and in combination with chemotherapy is warranted. No significant financial relationships to disclose.