bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secondary malignancies developing during metastatic breast cancer treatment
Authors: Nikolic N. M. , Tomasevic Z. , Jelic S. 
Published: August 2020

e12020 Background: Secondary malignancies (SM) developing during metastatic breast cancer (MBC) are obviously more complicated for diagnosis, potential surgery and for further MBC treatment. However, the frequency of SM during MBC is not well explored, in contrast to SM after nonmetastatic BC. The aim of this paper is to determine frequency of SM in MBC patients and to determine the percentage of surgically treated SM. Methods: Hospital charts of BC patients were retrospectively analyzed at the Institute for Oncology and Radiology of Serbia. Patients who developed SM at any time point after BC were included in this analysis. Patients with contra-lateral BC and acute leukemia were excluded. Patients with SM during MBC were separately analyzed. Results: A cohort of 50 BC patients with SM was identified. Median age was 50 (range 32–78 years) median time to SM was 65.3 months (range 1–276). Forty-six patients had histological confirmation of SM. In 30 patients SM developed during treatment for MBC. Four SM were not confirmed by biopsy due to SM site or high burden of MBC. Median age was 53.4 years (range 34–74), median time to SM development was 78.9 months, and median time to BC metastases was 60.1 months. The most frequent SM in MBC patient were lung (5), endometrial (4, all treated with tamoxifen), ovarian (3), thyroid (3), cervical (3), and colon carcinoma (2). Only 14 patients with SM (14/30: 46%) could be treated with radical surgery and SM did not influenced further MBC treatment. Conclusions: According to our experience, SM develops more frequently in MBC than in non MBC patients, representing 60% (30/50 patients) of all SM in BC patients; 46.6% (14/30) of SM diagnosed during MBC could be surgically resected, and does not influence further MBC treatment. No significant financial relationships to disclose.
The combination of capecitabine and cyclophosphamide for metastatic breast cancer patients
Authors: Suzuki M. , Kimijima I. , Ishii M. 
Published: August 2020

e12025 Background: Capecitabine (X) is converted into 5-FU by thymidine phospholylase (TP). Cyclophosphamide (C) has been shown to make TP higher in the preclinical study. Therefore, the combination of capecitabine and cyclophosphamide (XC) is thought to have a synergistic activity. We explored the efficacy of XC for metastatic breast cancer patients. Methods: 50 metastatic breast cancer patients were treated with XC in our medical center between April 2004 and December 2008. Median patient age was 58 years old (range: 34–79 years old). 36 patients were postmenopausal. X was 1675mg/m2 days 1–21 and C was 67mg/m2 days 1–14 on a 28-day cycle in all-oral combination. This therapy was continued until progression of disease or unacceptable toxicities occurring. Results: Median time to treatment failure was 28 weeks (range: 2–158 weeks). 9 patients were not evaluable for tumor response. Among 41 evaluable patients, complete response (CR) was observed in 2.4% (1 patient) and partial response (PR) was 29.2% (12 patients). Stable disease (SD) was 41.4% (17 patients) and progression of the disease (PD) was 26.8% (11 patients). The objective response rate (CR+PR) was 31.7% and the overall clinical benefit (CR+PR+SDÅÜ24 weeks) was 53.6%. Significant toxicities were uncommon: grade 3 toxicities were encountered for neutropenia in 1 patient, anorexia in 1 patient and hand-foot syndrome in 2 patients. Conclusions: XC is an effective regimen in metastatic breast cancer, and this therapy is of an easy administration and very well tolerated. No significant financial relationships to disclose.
Brain metastases (BM) in breast (BC) and lung cancer (LC) patients
Authors: Braverman A. S. , Hengel K. , Choi J. , Nwokedi E. , Sidhu G. , Weedon J. , Axiotis C. , Song X. 
Published: August 2020

e12029 Background: Most BM arise from BC or LC. Few studies compare their attributes and distribution, though BC BM have been reported to more often involve the cerebellum. Methods: Brain scanning was for clinical evidence of BM. Contrast-enhanced computer-automated tomograms (CT) or magnetic resonance images (MRI) of brains of all BC and LC patients irradiated for BM between 1996 and 2008 were reviewed. BC epidermoid growth factor receptor2 (HER-2) expression was determined. Results: Data was from 63 BC and 59 LC patients; 58% of the BC and 55% of the LC patients had MRIs. MRIs showed more cerebellar BM (p = 0.047). Primary to BM diagnosis intervals were shorter for LC than for BC patients (p = 0.001), but LC BM were more edematous (0.019). BC patients had more cerebellar BM (p = 0.004) than LC patients, and more BM in the cerebellum only (p = 0.017). LC patient gender and small cell histology did not correlate with cerebellar BM. Both cerebrums and cerebellums of BC patients had more BM than those with LC (p = 0.020; 0.013). Cerebellar BMs were more frequent in brains with more cerebral BM (p = 0.0020). Amongst BC over-expressing HER-2 was a trend to more cerebellar BM (p = 0.072). Conclusions: LC BM, which elicit more edema, produce symptoms earlier than BC BM. There are larger numbers of BC BM, perhaps due to BC's longer disease course and responsiveness to therapy. BC causes more cerebellar mets than LC, often without cerebral BM. This may be due both to the larger number of BC BM, and a predilection for the cerebellum. Periodic brain MRI, more sensitive than CT to posterior fossa lesions, may be indicated in some BC patients, and early radiation may control multiple small BM. No significant financial relationships to disclose.
Dosimetry study of a phase II multiple-dose intracavitary administration of 131I-TM601 in adult patients with recurrent high-grade glioma
Authors: Shen S. , Nabors L. B. , Raizer J. J. , Fiveash J. B. , Spies S. , Costello R. , O’Neill A. M. 
Published: August 2020

e13006 Background: Postoperative radiotherapy for glioma has been shown to improve survival with increased radiation doses. Dose escalation of external beam radiotherapy or brachytherapy is limited by normal brain radionecrosis. Radiolabeled targeting molecules can deliver localized radiation to tumor and reduce normal brain radionecrosis. TM601, or synthetic Chlorotoxin, is a peptide derived from scorpion venom that specifically binds to tumor cells. Here we report dosimetry results of an imaging sub-study of a phase II trial, in which weekly doses of 131I-TM601 were infused into surgically created tumor resection cavities for 3 or 6 weeks. Methods: Five out of 76 patients treated in a phase II trial were imaged after receiving 1, 3, or 6 doses of 40 mCi/0.8 mg 131I-TM601 intracavitarily. For each imaging study, 5 sequential SPECT images (1–168 hour) were registered with MRI to determine the 131I-TM601 radiation dose to the 2-cm tumor cavity margin. Five sequential body scans were also acquired to determine 131I-TM601 radiation dose to extra-cranial organs. Results: 131I-TM601 is a rapidly penetrating and clearing radiolabeled peptide. The median residual activity in the cavity at 7 days post injection was 8.4%. Median radiation dose to the cavity margin was 121 cGy/mCi and ranged 52- 338 cGy/mCi in 5 subjects. The median coefficient of variation (intra-patient inter-fraction) for the 2-cm margin dose was 14.7% and ranged 7.1–18.9%. Median tumor cavity volume was 11.4 mL, and ranged 5.2 - 35.5 mL. There was no observed correlation between the 2-cm margin dose and the cavity volume. Median radiation dose to thyroid, kidneys, red marrow, and body was 8.3, 1.3, 0.4, and 0.6 cGy/mCi, respectively. Conclusions: Radiation dose ratio for 2-cm cavity margin-to-normal tissues was quite high. While intra-patient reproducibility was relatively good, cumulative effect of the residual activity was only meaningful within a week. These results support the multi-dose fractionation scheme for 131I-TM601 to minimize normal tissue toxicity, including radiation necrosis, and extend continuous irradiation to clinical or sub-clinical residual tumor cells after surgery. [Table: see text]
Phase II study: WBRT ±temozolomide (TMZ) in patients with multiple brain metastases from non-small cell lung cancer (NSCLC)
Authors: Marosi C. , Elandt K. , Preusser M. , Dieckmann K. , Nevinny M. , Knocke-Abulesz T. , Pfeifer W. , Stockhammer G. , Hammer J. , Zielinski C. C. 
Published: August 2020

e13008 Background: Brain metastases cause increasingly morbidity and mortality in patients with NSCLC. In a multicentric Austrian phase II study, we investigated feasibility and toxicity of the addition of temozolomide to whole brain radiotherapy (WBRT) in patients with multiple brain metastases of NSCLC. Methods: Consenting patients with previously untreated, multiple, and measurable brain metastases from histologically confirmed NSCLC were eligible if they were 18 years or older, were at least in RPA (recursive partitioning analysis class) class II and showed adequate organ function. Treatment consisted of WBRT (arm A) +TMZ 75mg/m2 during radiation, followed at day 28 by TMZ 100 mg/m2 day 1–14, q28 for six cycles (arm B). The primary endpoint was objective radiographic response in CNS 10 weeks after the end of WBRT. Results: 35 patients (14 women) aged 35 to 86 years, median 65 years were randomized. Eight patients were in RPA class I and 27 were in RPA class II. 13 patients were enrolled in arm A and 22 in arm B. Toxicity was mainly haematological with WHO grade 3 and 4 thrombocytopenia observed in 0/13 versus 3/22 patients, leucocytopenia in 0/13 versus 1/22 patients, and lymphocytepenia in 12/13 and 7/22 patients respectively. No severe nonhematologic toxicity occured in arm A, whereas two episodes of transient hepatic toxicity were reported in arm B. 10/13 patients of arm A and 13/22 patients of arm B showed progressive disease and dropped out of study before restaging 10 weeks after completion of WBRT. Two patients of arm A had progressive disease in CNS, all other progresses noted were systemic. At restaging there were 2 PR, 1 SD in arm A, and 1 CR, 3 PR, 6 SD in arm B. Median time to progression was 40 days in arm A and 74 days in arm B (p = 0.027). Conclusions: The addition of temozolomide to WBRT in patients with brain metastases of NSCLC yielded acceptable toxicity and promising activity, although systemic progression remained the main cause of morbidity and mortality. [Table: see text]
Case-control study of long-term survivors of glioblastoma
Authors: Quant E. C. , Silver M. , Yip S. , Ryg P. , Provencher K. , McCormack K. , Louis D. N. , Betensky R. , Nutt C. , Batchelor T. T. 
Published: August 2020

e13021 Background: Survival of patients with glioblastoma (GBM) remains poor. However, a small percentage of GBM patients live ≥ 3 years. Relatively little is known about the patterns of care and outcomes of these long term survivors relative to GBM patients with standard or short-term survival. Methods: Nested case-control study of long term survivors (≥ 36 months), short term survivors (≤ 6 months) and standard survivors (> 6 months but < 36 months). Pathology was confirmed in all study subjects by a single neuropathologist. Each long term survivor (LTS) was matched to a short term survivor (STS) and 3 standard survivors (SS) by the well-established prognostic factors, age and postoperative Karnofsky Performance Status. Clinical characteristics, treatment regimens and outcomes were reviewed. Conditional logistic regression models were used to assess potential associations between baseline factors and the probability of long or short term survival. Results: Matching yielded 23 LTS with 23 STS and 69 SS. Patient characteristics are summarized in the table below. Conclusions: Controlling for the well-established prognostic factors of age and performance status, long-term GBM survivors differed significantly from short-term GBM survivors based on tumor location and extent of resection. However, there were no significant differences in baseline factors between long-term survivors versus standard survivors in this analysis. Short-term GBM survivors differed from standard survivors by tumor location and extent of resection. Molecular factors are being assessed in these groups as potential contributors to these survival differences. [Table: see text] [Table: see text]
Temozolomide (TMZ) and bevacizumab (BV) as initial treatment for unresectable or multifocal glioblastoma multiforme (GBM)
Authors: Peters K. , Desjardins A. , Reardon D. A. , Perry S. , Herndon J. E. , Bailey L. , Friedman A. H. , Friedman H. S. , Bigner D. D. , Vredenburgh J. J. 
Published: August 2020

e13025 Background: GBMs are vascular tumors and inherently resistant to therapy. The prognosis for patients is poor with a median survival of 9–15 months. Patients with unresectable or multifocal GBMs have an even poorer prognosis, with a median survival of 6–8 months. Given the angiogenic phenotype of GBM, we conducted a phase II trial of upfront BV and 5-day TMZ in newly diagnosed unresectable or multifocal GBMs. Methods: Patients had histologically documented newly diagnosed GBMs that were unresectable or multifocal. Patients received up to 4 cycles of temozolomide at 200 mg/m2/d days 1–5 and BV at 10 mg/kg on days 1 and 14 in a 28 day cycle. An MRI was performed after every cycle and patients continued on therapy as long as there was no tumor progression, grade 4 non-hematologic toxicity or recurrent grade 4 hematologic toxicity after a dose reduction to 150 mg/m2/d. The primary endpoint was tumor response using the modified MacDonald criteria plus FLAIR and T2 sequences to evaluate non-enhancing tumor. Results were evaluated by two independent reviewers. Results: 41 patients were enrolled between October 2007 and September 2008 and 31 patients were analyzed after completion of cycle 2. As the best response, there were 8 (25.8%) partial responses, 19 (61.3 %) patients with stable disease, and 4(12.9 %) had disease progression. 19 of the 41 patients enrolled completed four cycles without tumor progression. The regimen was tolerable, with 3 grade 4 hematologic toxicities including neutropenia and thrombocytopenia. There were 2 grade 4 non-hematologic toxicities, including pulmonary embolism. There were two CNS hemorrhages. The median PFS was 3.6 months (2.9 months, 4.4 months) and the median OS was 4.5 months (3.7 months, 5.3 months). Conclusions: Upfront temozolomide and bevacizumab was well tolerated, but synergistic chemotherapy or growth factor inhibitors need to be added to produce meaningful clinical benefit, particularly for unresectable or multifocal GBM. No significant financial relationships to disclose.
The temozolomide O6-methylguanine-DNA methyltransferase (MGMT) study: A phase II trial to evaluate the effect of low-dose preoperative neoadjuvant temozolomide on brain tumour MGMT activity in glioma patients
Authors: Del Maestro R. F. , Siu V. , Seyed Sadr M. , Alshami J. , Sabau C. , Seyed Sadr E. , Samani A. , Assadian S. , Greaves K. , Pouliot J. 
Published: August 2020

e13027 Background: Epigenetic methylation of the O6-methylguanine-DNA methyltransferase (MGMT) DNA repair gene promoter in tumor tissue from glioblastoma multiforme patients is associated with improved survival after treatment with radiotherapy plus concomitant and adjuvant temozolomide (TMZ). We hypothesized that MGMT promoter methylation mosaicism exists in glial tumors and would affect response to TMZ. Methods: This is a nonrandomized, prospective, open-label, two cohort, single-center phase II study. Twenty-three patients with brain tumors detected by MRI scan and suspected to be gliomas were evaluated. All eligible patients were treatment naive and were self-selected into a TMZ group or a control group. The primary goal of the study was to evaluate the effect of TMZ 75 mg/m2 daily prior to surgery on the brain tumor MGMT expression. Secondary endpoints included safety, tolerability, and MGMT promoter methylation mosaicism in glial tumors. Samples were obtained from multiple regions of each tumor intra-operatively and were analyzed by methylation specific PCR. Results: Our results on MGMT promoter methylation demonstrate that three groups of patients can be identified: Type I: all sites assessed in the tumor demonstrate no methylation of the MGMT promoter; Type II: all sites demonstrate high levels of MGMT promoter methylation; and Type III: a mixed promoter methylation pattern is observed. Conclusions: These results suggest that 1) preoperative neoadjuvant temozolomide is not associated with increased postoperative complications; 2) glial tumors can have very heterogeneous areas of MGMT promoter methylation; and 3) three patterns of MGMT promoter methylation can be discerned. This experimental paradigm may be a useful experimental platform for the assessment of the effect of new drugs at the tumor level. [Table: see text]
Enzastaurin (ENZ) before and concomitant with radiation therapy (RTX), followed by ENZ maintenance therapy in patients with newly diagnosed glioblastoma (GBM) without hypermethylation of the O6-methylguanyl DNA-methyltransferase (MGMT) promoter: A multicenter, open-label, uncontrolled phase II study
Authors: Wick Wolfgang W. , Combs S. E. , Platten M. , Weller M. , Ohnmacht U. , Stoffregen C. , Thornton D. 
Published: August 2020

e13038 Background: There is an unmet need to improve efficacy outcome for GBM patients without hypermethylation of the MGMT promoter. Preclinical data indicated a potential benefit of ENZ, an oral serine/threonine kinase inhibitor, together with RTX (Tabatabai et al; Ann Neurol 61: 2007). In a run-in phase of this phase II study the feasibility of once or twice daily ENZ dosing was evaluated. The split dose results in higher exposure. The results of the run-in phase are presented. Methods: Patients (pts) with newly diagnosed supratentorial GBM were entered. The first regimen administered once daily ENZ (500 mg QD) before and concomitant with standard radiotherapy at a dose of 60 Gy (2 Gy, 5 days a week). As no dose-limiting toxicities occurred in the first 3 pts, another 6 pts were enrolled into the second regimen, twice daily ENZ (250 mg BID) with RTX. ENZ is given until progression afterward. Results: Between 10/07 and 07/08 a total of 9 pts were enrolled. Mean treatment duration was 9.3 weeks for ENZ, and 6.3 weeks for RTX. No drug-related grade 3/4 toxicity was reported. The only laboratory toxicity CTC grade 3 (low potassium) and 1 serious adverse event (erysipelas) were reported in the BID regimen. No pts discontinued in the first 9 weeks, no deaths in this period. Conclusions: Following the results of the run-in phase, the BID regimen was chosen for the ongoing study. [Table: see text] [Table: see text]
A phase I study investigating the combination of orally bioavailable platinum and nanoparticle albumin-bound paclitaxel in advanced solid tumors
Authors: Deshpande H. A. , Gettinger S. , Rowen E. , Abu-Khalaf M. M. , Clarke J. , Burns A. J. , Kelly W. K. 
Published: August 2020

e13501 Background: The combination of a taxane and a platinum agent is considered a standard chemotherapy regimen for many solid tumors. Adverse effects often limit the administration of these drugs. Satraplatin (S) is an orally bioavailable platinum agent with a similar spectrum of activity to other platinum analogs, but less renal or neurological side effects. The nanoparticle albumin-bound paclitaxel (A) has shown greater efficacy and less toxicity than Cremophor-based paclitaxel as a single agent in the treatment of breast cancer. The primary aim of this study was to determine a safe dose for the combination of S +A and to investigate if there were pharmacokinetic (PK) interactions between S + A in patients (pts) with advanced malignancies. Methods: Cohorts of 3–6 pts were enrolled and treated. Escalating oral doses of S (40–60- 80mg) were administered on days 1–5 in combination with intravenous fixed dose of A (100 mg/m2) on 1, 8, and 15 of a 28 day cycle. Prior to cycle 1 all patients received A day -14. Blood samples for PK studies were drawn with the day -14 and Day 1 treatments. Results: To date 15 pts (2 renal, 3 prostate, 2 bladder, 1 hypopharyngeal, 1 mesothelioma, 1 colorectal, 1 melanoma and 2 leiomyosarcomas) with a median age 51 (range 37 - 78 yrs) have been treated in 3 cohorts. Doses were escalated as follows; Cohort 1 (40 (S)/100(A), n = 4), Cohort 2 (60/100, n = 7), Cohort 3 (80/100, n = 3). 1 patient (testicular cancer) intended for cohort 1 was a screen failure. Two patients in cohort 3 had grade 3\/4 neutropenia (DLT). An additional 4 patients were treated in cohort 2 without DLT and this dose level was determined to be the MTD. Most common severe adverse events were Grade 3 anemia (5%), neutropenia (22%), fatigue (5%) and dehydration (5%). 3 patients had grade 4 neutropenia, 2 in cycle 1 of cohort 3 and 1 in cycle 2 of cohort 2. To date 6 patients had progressive disease, 4 had stable disease (3.8 months), 3 patients (2 with prostate cancer and 1 with hypopharyngeal cancer) had a partial response. Conclusions: The combination of A plus S was well tolerated and the recommended dose for phase 2 studies is paclitaxel 100 mg/m2 weekly for 3 weeks plus satraplatin 60 mg/m2 daily for 5 days every 28 days. PK analyses will be presented. [Table: see text]
Final results of phase I and pharmacokinetic study of SJG-136 administered on a daily x 5 schedule
Authors: Kadia T. M. , Faderl S. , Estrov Z. , Konopleva M. , George S. , Lee W. , Puzanov I. , Chen A. , Kantarjian H. , Ravandi F. 
Published: August 2020

e13506 Background: SJG-136 is a pyrrolobenzodiazepine dimer that forms covalent DNA crosslinks in a sequence-specific manner in the minor groove. In vitro testing demonstrated a broad pattern of antitumor activity in sub-nmol concentrations. A phase I study in patients (pts) with solid tumors revealed clinical activity, defined MTD as 30 mg/m2/d administered on daily x 3 schedule, and confirmed manageable toxicity. Here we report the results of a CTEP-sponsored phase I trial of SJG-136 administered on a daily x 5 schedule in pts with relapsed or refractory (R/R) leukemias. Methods: Previously treated pts with R/R acute leukemias (AML, ALL, high risk MDS, CML blast phase) or R/R CLL with adequate organ function and ECOG performance status of ≤ 2 were eligible for the study. The starting dose level was 6 mcg/m2 given intravenously daily x 5 days on a 21 day cycle. Pts were sequentially enrolled in cohorts of 3 and the dose was escalated in a classic 3+3 schema at the dose levels: 6, 12, 24, and 36 mcg/m2. Repeat courses and intrapatient dose escalation were allowed. Results: Sixteen pts (11M, 5 F) were enrolled on the study. The median age of the patients was 53 (21–84). Thirteen (81%) pts had R/R AML, and 3 (19%) had R/R ALL of which 5 (31%) had diploid and 6 (38%) had adverse cytogenetics. Median number of prior therapies was 3 (2–6). Pts enrolled at each dose level (mcg/m2) were: 6 (3 pts), 12 (5 pts), 24 (4 pts), 36 (4 pts). The median number of cycles delivered was 1 (0–5). The dose of 36 mcg/m2 was found to be above the MTD, with the DLT being grade 3 soft tissue edema. Other manifestations of vascular leak including grade I, II hypoalbuminemia, edema, and pleural effusions were seen in a number of patients starting at dose level 24 mcg/m2 and above. Other non-dose limiting toxicities included nausea, dyspnea, fatigue, bloating, and insomnia. One pt had a PR, 8 pts had stable disease, and 6 had progression. Pharmacokinetic characteristics in this population will be reported. Conclusions: SJG-136 is safe and active in patients with advanced leukemias. Edema and other vascular leak syndromes are characteristic toxicities of the agent at higher dose levels. 24 mcg/m2 is the recommended phase II dose for the daily x 5 schedule. No significant financial relationships to disclose.