bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of response to primary systemic therapy (PST) with docetaxel and trastuzumab in HER2-positive breast cancer
Authors: Rao M. , Griggs J. J. , Schiffhauer L. M. , Messina P. , Bourne P. , Ahrendt G. M. 
Published: March 2020

11100 Background: The purpose of this study was to assess the relationship between estrogen receptor (ER) status, amplification of HER-2, and tumor response to PST with docetaxel and trastuzumab in breast cancers positive for HER-2 by immunohistochemistry (IHC). Long-term disease-free survival data are also reported. Methods: Eligible patients were those with T2 or T3 tumors and overexpression of HER-2 via IHC. Docetaxel 100 mg/sq m q. 3 weeks × 4 with growth factor support and weekly trastuzumab × 12 were given before surgery. The Miller-Payne system was used to define pathologic responses (PR) in the excision specimen (0, 1, 2 - no/minimal response; 3 - 4 partial response, pPR; 5 - complete response, pCR). Adjuvant therapy was given at the discretion of the treating oncologist. Results: Of 22 enrolled patients, 19 were assessable. 17 of the 19 subjects had subsequent FISH confirmation of HER-2 status. Six subjects (31%) had a pCR. Of these, 5 had strong amplification of HER-2 and 5 had tumors that were ER-negative. A pPR occurred in an additional 2 subjects (10%). Of the 11 subjects who had no or minimal PR (Miller-Payne 0 - 2), 8 were found to have no amplification for HER-2 and 9 had tumors that were ER-positive. Postoperative (adjuvant) chemotherapy was given to 17 patients. All 12 patients with ER-positive tumors received adjuvant hormonal therapy. Three patients had an asymptomatic decline in left ventricular ejection fraction (LVEF) of 10 - 15% after anthracycline containing chemotherapy, and one had symptomatic non-ischemic cardiomyopathy of unclear etiology 4 years after completion of study therapy and an anthracycline. With a median follow up of 56 months, all 19 participants are alive and disease-free. Conclusion: PST with a 12-week course of trastuzumab and docetaxel is safe and effective, produces a substantial pCR rate, and may result in excellent long-term recurrence-free and overall survival. The subset of patients with tumors that were IHC-positive, but FISH-negative for HER-2, and ER-positive had minimal or no response to therapy, highlighting the importance of identifying patients most likely to respond to trastuzumab-based regimens. [Table: see text]
Phase I trial of alvespimycin (KOS-1022; 17-DMAG) and trastuzumab (T)
Authors: Miller K. , Rosen L. S. , Modi S. , Schneider B. , Roy J. , Chap L. , Paulsen M. , Kersey K. , Hannah A. , Hudis C. 
Published: March 2020

1115 Background: Alvespimycin (A) inhibits the activity of Hsp90, resulting in degradation of client proteins, such as the HER2 receptor. In vivo, Hsp90 inhibition induces rapid degradation of HER2 with loss of pAKT, cyclin D2 and tumor growth inhibition. Methods: Pts receive standard weekly doses of T followed by A in escalating doses via IV doses over 1 hr. Define the recommended dose (RP2D), toxicity and signs of activity of T+A in pts with solid tumors. PK: assessed after the 1st and 4th infusion. PBLs: purified to investigate changes in intracellular signaling proteins by immunoblot. The RP2D will produce DLT in no more than 1/6 evaluable pts. Results: 21 pts enrolled in 3 cohorts (60, 80 and 100 mg/m2). Median age 53 yrs, range 31–75; median KPS 90; prior regimens not including hormonal therapy: median 6, range 1–13; prior T-regimens for MBC pts: median 3, range 0–9. Diagnoses: HER2+ MBC (n=18), ovarian (n=3). DLT was observed at the highest dose, consisting of 1 pt with hypoxia and ↓LVEF; an additional pt at this dose had Grade 3 ↑AST, however ↑hepatic metastases and ascites were observed. Drug-related toxicity: diarrhea (60%), fatigue, headache (both 45%), nausea, arthralgias (both 40%), dry eye and pain in extremity (both 25%); all Grade 1–2 severity except 1 episode of Gr3 fatigue and Gr3 diarrhea. PK (n=18): t½ 17.7 hr (32%CV); Clearance 18.1 L/hr (46%CV); Vz 438L (42%CV); no change upon weekly dosing. AUCinf/Cmax (100 mg/m2): 14268 ng*hr/mL (60%CV) and 2233 ng/mL (23.5%CV). HER2+ MBC activity: 1 pt (13 prior regimens; 3x T and 1x lapatanib) with evaluable disease showed near complete resolution of lung metastases by CT/PET with significant improvement in dyspnea; 3 pts with HER2+ MBC with SD (4, 5 and 7+ months). Ovarian CA activity: 1 pt (HER2 unknown; 13 prior regimens; 11+ months on-study) with evaluable disease showed near complete resolution of ascites and pleural effusion at end of Cycle 2 with ↓83% CA125. Dose-dependent increase in Hsp70 in PBLs; at 80 and 100 mg/m2, Hsp70 induction was maintained prior to successive weekly doses. Conclusions: Combination of T+A has signs of activity in H-refractory HER2+ MBC and refractory ovarian cancer. Definition of RP2D dose is pending. Toxicity has been manageable. No significant financial relationships to disclose.
Phase 2 study of MKC-1 in patients (pts) with metastatic breast cancer (MBC) who have failed prior therapy with an anthracycline (A) and taxane (T)
Authors: Sylvester L. , Laufman L. , Jabboury K. , Saleh M. , Tkaczuk K. , Volterra F. , Arnott J. , Hannah A. , Sidor C. , Miller K. 
Published: March 2020

11508 Background: MKC-1 (previously Ro 31–7453) is a novel cell cycle inhibitor with significant in vitro and in vivo activity against a wide range of tumor cell lines, including multi-drug resistant cell lines. Proteins identified as binding targets of MKC-1 include microtubules (colchicine binding site) and members of the importin-β family (proteins that play a critical role in nuclear transport and spindle formation). Objective responses (ORs) were observed in heavily pre-treated breast and NSCLC pts (Trigo Perez ASCO’03 A62; Kurup ASCO’03 A2725) treated at a dose of 95 mg/m2 BID given 14 days every 4 weeks with little toxicity. Salazar et al (2004 CCR 10:4374) recommended a higher oral dose (125 mg/m2 BID) on this schedule for further studies. This phase 2 trial is exploring the higher dose to maximize potential anticancer activity. Methods: Pts with MBC who had failed prior A and T and met eligibility criteria received MKC-1 at 125mg/m2 BID x 14d every 4 weeks. Pts with known treated and stable CNS metastases could enroll. Primary objective: OR by RECIST. Should 2 or more of the first 23 evaluable pts have an OR, enrollment will continue to 53 pts. Dose escalation/reductions are required based on toxicity (primarily neutropenia). Results: To date, a total of 20 pts have been enrolled (4 active in Cycles 1–5+). All female; median age/KPS of 60/90. 19% / 13% had received A / T in the neo/adjuvant setting; others had received A / T for metastatic disease. To date, a total of 48 cycles (median 2, range 1–8) were administered; of pts proceeding into Cycle 2, 40% and 20% had the dose increased or reduced, respectively. Severe drug-related toxicity (n=17) was observed in 3 pts (18%): ↑AST/ALT in 2 pts and parathesias in 1 pt. Drug related toxicity: nausea (47%), ↑ALT, diarrhea (both 24%), anemia, ↑AST, cough, fatigue, neutropenia and vomiting (all 18%). Two pts discontinued due to toxicity. One pt had complete resolution of measurable disease (1st observed after Cycle 4, confirmed after Cycle 6 with withdrawal for a new lesion at Cycle 8). An additional 2 pts had stable disease for 5 cycles (1 pt remains active). Conclusions: MKC-1 is well tolerated at the initial recommended dose for this schedule. Activity is observed in pts previously treated with A/T for MBC. No significant financial relationships to disclose.
Does the addition of COX-2 inhibitors alter the resistance to aromatase inhibitors?
Authors: Gemici C. , Salepci T. , Bese N. , Gocen E. , Yaprak G. , Mayadagli A. 
Published: March 2020

11511 Background: This study aimed to investigate whether the addition of COX-2 inhibitor to aromatase inhibitor alter the resistance to aromatase inhibitor, developed during first or second line hormonal treatment of estrogen (ER) and/or progesterone receptor (PR) positive metastatic breast cancer cases. Methods: ER and/or PR positive breast cancer patients with known high baseline CA 15–3 levels due to the tumor and receiving a first or second line (after first line tamoxifen) aromatase inhibitor due to soft tissue (lymphatic tissue, skin) or bone metastasis were evaluated in this study. A recurrent increase in CA 15–3 levels without tumor progression following an initial decrease in CA 15–3 levels was observed in 7 patients and this was considered as resistance to the aromatase inhibitor. For this reason, a COX- 2 inhibitor was added to either letrozole (5/7) or anastrozole (2/7) treatment. The aromatase inhibitor and COX-2 inhibitor combination (celecoxib 200 mg bid, 5/7 cases; rofecoxib 50 mg od, 2/7 cases) was used for 3 months. CA 15–3 levels and tumor response of these 7 cases was re- evaluated at the end of 3 months. Results: None of the seven cases had a decrease in CA 15–3 levels following the 3 months of aromatase inhibitor plus COX-2 inhibitor combination treatment, instead all cases had their levels increased. In addition, none of the 7 cases had clinical or radiological tumor response, all had tumor progression. Treatment was continued by either third line hormone treatment (4/7) or chemotherapy (3/7). Conclusions: COX-2 inhibitors are suggested to potentiate endocrine treatment since the overexpression of COX-2 contributes to the increased expression of aromatase in the breast tumor tissue. Thus, the combination of an aromatase inhibitor and a COX-2 inhibitor may be useful in the hormonal treatment of breast cancer. However, present study failed to demonstrate alteration of the developed aromatase resistance by the addition of a COX-2 inhibitor. No significant financial relationships to disclose.
The role of HER2/neu, estrogen, and progesterone receptor status in the risk and survival of breast cancer leptomeningeal metastasis
Authors: Grewal J. , Groves M. D. , Bekele B. N. , Yung W. A. 
Published: March 2020

11512 Background: Leptomeningeal metastasis (LM) is a dreaded complication of breast cancer with a median survival of approximately 4 months from the time of LM diagnosis. HER2/neu (HER2), estrogen (ER), and progesterone (PR) receptor status are routinely used to determine prognosis and guide treatment. There is emerging data regarding the influence of these receptors on the risk and prognosis of parenchymal brain metastasis. However, the role of these receptors in LM is unknown. We performed a retrospective analysis of 61 patients with breast cancer to determine the risk and survival of LM as a function of receptor status. Methods: Of patients with breast cancer evaluated in our department for possible LM between 2003 and 2006, those requiring CSF analysis were included in this study. Of these 61 patients, 27 were diagnosed with LM and 34 were found to be negative for LM, based on analysis of CSF and MRI. Information regarding HER2 receptor status was unavailable in 3 patients (1 with LM) due to technical issues with the assay. ER, PR, and survival data were available for all patients. Odds ratio of developing LM was calculated based on each receptor status. The Fisher exact test was used to determine significance. For the 27 patients with LM, receptor status was used to stratify survival from the time of LM diagnosis using Kaplan-Meyer analysis; significance was evaluated using the log-rank test. Results: The odds ratios of developing LM in patients with positive HER2, ER, and PR were 1.89, 0.32, and 0. 825, respectively. P values were 0.378, 0.056, and 0.799. In the 27 patients with LM, survival from the time of LM diagnosis was not significantly different when stratified by receptor status; p values were 0.983, 0.317, and 0.625 respectively. Conclusions: Our retrospective analysis suggests that HER2/neu-positive and ER-negative breast cancer may be associated with a higher risk of LM, although this approached statistical significance only for ER. For patients with confirmed LM, there were no significant differences in survival based on receptor status, although there was a trend favoring ER-positive disease. Larger studies are needed to clarify the role of these receptors in the risk and prognosis of breast cancer LM. No significant financial relationships to disclose.
Variation in prognostic factors in hormone receptor-positive breast cancer patients who responded to hormonal therapy and those who did not: A retrospective analysis
Authors: Jain A. , Bapsy P. , Attili S. V. , Batra U. , Dasappa L. , Govindbabu K. , Sajeevan K. , Saini K. V. , G A. 
Published: March 2020

11514 Background: Hormone receptor positive patents historically had a better prognosis than their receptor negative counterparts when other parameters are balanced. However not all the patients expressing Estrogen and progesterone respond well to the hormonal manipulation. Therefore we thought of doing a retrospective analysis of our hospital data to find out the differences in the prognostic factors in therapy responders and non responders. Methods: The study was conducted at tertiary care cancer center from India. Between 2002–2003 a total of 120 breast cancer patients who expressed either Estrogen receptor (ER) or progesterone receptor (PR) were analyzed. Only patients with metastatic breast cancer were analyzed. The patients were treated with our standard institutional protocol at the beginning according to the stage of the disease. The details and baseline characters were shown in table . Results: The responders tend to be post menopausal, having low grade, node negative tumors, expressed both ER and PR, and had long interval from the date of initial diagnosis. However tumor size and the site of metastasis (visceral vs. non visceral) did not alter the outcome to hormone therapy. Conclusion: patients who are having higher age, lower tumor grade, lower number of nodes, longer disease free interval after adjuvant therapy and expressing both receptors tend to respond to hormone therapy better than those who had the opposite characters. However as thought earlier, presence of visceral metastasis or larger tumors at the time of initial diagnosis dose not preclude response to hormonal manipulation. [Table: see text] No significant financial relationships to disclose.
Tinzaparin prophylaxis in brain tumor patients
Authors: Bohlin C. W. , Reardon D. A. , Desjardins A. , Quinn J. A. , Rich J. N. , Bota D. A. , Goli K. , Friedman H. S. , Vredenburgh J. J. 
Published: March 2020

12506 Background: Thromboembolic disease is the second leading cause of death in brain tumor patients. Various studies have documented a 20–40% risk of deep vein thrombosis and / or pulmonary embolus in brain tumor patients. When used as prophylaxis, Tinzaparin, a low molecular weight heparin with factor Xa activity, has a low complication rate and low incidence of bleeding complications. With the anticipated benefit exceeding any risk, prophylaxis with Tinzaparin may be safe and effective. Methods: A phase II trial of prophylactic tinzaparin for newly diagnosed brain tumor patients has completed accrual at 40 patients. A fixed daily dose of 4500 IU subcutaneous tinzaparin was given beginning a minimum of 48 hours post-operatively and a maximum of 4 weeks post-operatively. Patients consented to take tinzaparin daily for 12 months. Weekly blood counts were monitored during chemotherapy cycles. Tinzaparin was held if platelet count was <50,000 and resumed once the platelets were >100,000. Tinzaparin was discontinued in patients who began treatment with avastin. Results: Of 40 patients, 7 remain on treatment. Patients have taken tinzaparin for 4–52 weeks with a median of 21 weeks. One of the patients developed a grade 3 CNS hemorrhage and one had a grade 1 CNS hemorrhage, necessitating cessation of the tinzaparin, there have been no grade 4 or 5 CNS hemorrhages or treatment associated mortality. No patients developed = grade 2 systemic hemorrhages. One patient developed a deep venous thrombosis while taking tinzaparin, and three patients developed thromboembolic complications while off tinzaparin secondary to thrombocytopenia. One patient was taken off study for increased liver function tests, possibly secondary to tinzaparin. Conclusions: Thus far, daily prophylactic tinzaparin has proven safe and effective in decreasing the incidence of thromboembolic disease in brain tumor patients. We plan a phase III study upon the safe completion of the last 7 patients on this phase II study. No significant financial relationships to disclose.
A study of feasibility for setting up a dedicated brain tumor registry
Authors: Davidson S. J. , O’Neal K. , van Dellen J. , Roncaroli F. , Brock C. , Waldman A. 
Published: March 2020

12514 Background: Population-based tumor registries represent an invaluable resource for monitoring incidence and prevalence of cancer. Nevertheless, data generated is not always useful for deciding treatment protocols or running translational/clinical research. This is particularly true for rare cancers such as primary brain tumors. Moreover, benign or low grade tumors are usually excluded and information such as quality of life and efficacy of treatment not followed up. Finally, there is no agreement on the minimum dataset required. Here, we investigated the difficulties of setting up a dedicated BTR that can be supportive of research. Methods: We audited 1000 consecutive histologically proven adult cases operated between 1995–2005. This group included 734 gliomas, 246 meningiomas and 20 ependymomas. As minimum dataset, we considered demographics, presenting symptoms, site, neuroimaging findings, pathology/WHO grade, extent of surgery, post-operative treatment, relapses and cause of death. To avoid capture/recapture errors we cross-referenced four independent databases (histopathology, imaging, Cancer Specialist and hospital patient database). Results: Overall availability of data was 80% in 1995–2000 and 95% in 2000–2005 when electronic notes were introduced. Missing data were as follow: demographics: 0%; symptoms: 20%; site and neuroimaging 15%; incorrect diagnosis or grade update; 20%; extent of surgery: 5%; post-operative treatment: 15%; follow-up: 10%: cause of death: 15%. Data could not be interpreted in 20% of cases due to transcription errors and use of abbreviations. Conclusion: To fulfil requirements for clinical/translational research (GNOSIS), BTR needs i) dedicated national registries; ii) specialist and professional data collection; iii) registration at the time of pathological diagnosis. No significant financial relationships to disclose.
Phase I of high dose (HD) temozolomide (TMZ) with peripheral blood stem cell support (PBSCS) rescue in recurrent high grade glioma (HGG)
Authors: Frappaz D. , Pierga J. , Bay J. , Fabbro M. , Djafari L. , Sunyach M. 
Published: March 2020

12518 Background: Despite improvements obtained with frontline treatments prognosis of recurrent HGG still remains dismal. HD chemotherapy (CT) suggested a dose-effect relationship in lymphoma and germ cell tumors. HD of TMZ could be a promising way to overcome resistance of HGG to standard schedule of CT Methods: This phase I had as principal objective to determine the Maximal Tolerated Dose (MTD) of HD of TMZ with PBSCS rescue in patients with recurrent HGG under 60 year. The MTD was defined as dose level which 50% of patients (pts) treated experienced a DLT (Dose Limiting Toxicity).The dose escalation was planned for eight dose levels from 300 to 650mg/m2/day over 5 days with CSP reinfusion at D7 according to the Modified Continual Reassessment Method (MCRM). Treatment was administered for one cycle. Results: Eighteen eligible pts were treated with HD of TMZ, all had received prior radiotherapy, 11 pts previous CT. Overall HD TMZ was well tolerated for the 7 evaluated dose levels. The MTD was not yet reached. Not dose limiting toxicities were reported in 12 pts: grade 2: fatigue (6pts), cephalalgia (3pts), nausea (3pts) , skin eruption (2pts), mucositis, FUO, vomiting, diarrhea, zoster, dental abcess, lung infection, septicemia, hepatic. grade 3 bilirubinemia, grade 4 neutropenia (13pts) and thrombocytopenia (4pts). Dose Limiting Toxicities were reported in 2 pts, gr3 cytolysis at level 3 (400mg/m2/day ) 1pt and gr 3 arthritis at level 7 (600mg/m2) 1pt respectively . Main hematological toxicities were gr 4 neutropenia in 13 pts median duration was 8 days, 4 pts had gr4 thrombocytopenia lasting 5 days. All patients were evaluable for tumor response, 2 partial responses were observed at 550 and 600mg/m2 level, 5 pts had a stabilization and a disease progression was reported in 11 patients. Conclusions: This interim analysis demonstrated that HD of TMZ with CSP reinfusion is feasible and well tolerated in patients with recurrent HGG. Nevertheless limited activity reported could be related to a less depletion of O6 alkylguanine transferase with HD than with a protracted schedule. Accrual is still ongoing. No significant financial relationships to disclose.
High-dose methotrexate and ifosfamide for CNS relapse of aggressive lymphoma
Authors: Fischer L. , Korfel A. , Jahnke K. , Kiewe P. , Thiel E. 
Published: March 2020

12524 Background: CNS involvement is a grave complication of malignant lymphoma. Therapy traditionally includes intrathecal chemotherapy, radiotherapy and systemic chemotherapy for concomitant systemic lymphoma. However, optimal therapy has not been established thus far for CNS lymphoma. In this pilot study a combination of systemic high-dose (HD) methotrexate (MTX) and ifosfamide (IFO) was evaluated for toxicity and response rate. Methods: 10 patients (pts.) with CNS relapses of aggressive lymphoma (5 nodal DLBCL, 4 PCNSL/PIOL and 1 T-NHL) were treated. Nine pts. had intracerebral lesions, the meningeal compartment was involved in three. Three pts. had systemic manifestations. Median age was 63 years (32 - 83). Therapy consisted of 4g/m2 MTX (4h infusion on day 1) with dose adjustment for creatinine clearance (CC) < 100ml/min (CC/100 * 4g/m2) and 1.5 to 2g/m2/day IFO (3h infusion day 3 to 5). Supportive therapy included mesna and a leucovorin rescue beginning at 24h after start of MTX. Two pts. were treated with intrathecal chemotherapy before MTX/IFO. Results: A median of 4 cycles chemotherapy was administered. Treatment response was documented in 9 pts. (3 CR, 6 PR), and one patient had stable disease. The toxicity was mainly hematologic with grade 3/4 neutropenia in 6 pts., grade 3/4 thrombocytopenia in 4 pts. and grade 3 anemia in 2 pts. One pat. died from sepsis in neutropenia and one pat. with long-term corticosteroid therapy developed an aspergillus pneumonia grade 3. Nephrotoxicity grade 1/2 was observed in 6 pts.. Four pts. were further treated with HD chemotherapy followed by autologous stem cell transplantation or salvage radio-/chemotherapy. A median progression free survival of 6.5+ months (range 1–41+) for all pts. has been reached with persisting remission after 4 to 41 months in 5 pts.. Conclusions: Systemic combination therapy with MTX and IFO is feasible and exhibits a promising activity in CNS relapses of aggressive lymphoma. No significant financial relationships to disclose.