bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammatory and locally advanced breast cancer respond similar to operable breast cancer to neoadjuvant chemotherapy: Results from 278 patients with cT4a-d tumors of the GeparTRIO trial
Authors: Minckwitz G. Von , Kümmel S. , Vogel P. , Hanusch C. , Eidtmann H. , Hilfrich J. , Gerber B. , Huober J. , Costa S. D. , Loibl S. 
Published: March 2020

542 Background: Neoadjuvant chemotherapy is the treatment of choice in patients with T4a-c and inflammatory (T4d) breast cancer. However, data on large-scale, multicentre, prospective trials are missing. In the GeparTRIO study (SABCS 2006, abstr. 42) 278 of 2,090 patients with cT4a-c or T4d tumors were included as a separate stratum for inoperable disease for a prospectively planned analysis. Methods: Patients were treated with 2 cycles TAC (docetaxel 75 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2, q d 21). If tumor reduction was >50%, patients were randomized to receive 4 or 6 additional TAC cycles. If tumor reduction was less, patients were randomized to 4 additional TAC cycles or to 4 NX cycles (vinorelbine 25 mg/m2 day 1 + 8, capecitabine 2,000 mg/m2 day 1 14, q21). Efficacy endpoints were pCR-rate (no invasive and no non-invasive residuals in breast and lymph nodes) (primary), clinical response before surgery and breast conserving therapy (BCT) rate (secondary). Results: 95 (4.6%) T4d, 183 (8.9%) cT4a-c, and 1,767 (86.4%) T1–3 tumors were registered in GeparTRIO within 36 months. Patients with inoperable/operable tumors had a median age of 53.9/49.0 years, median cT size: 7.0/4.0cm, cN+: 75.6/52.0%, ductal: 76.3/78.4%, lobular: 14.0/13.5%, multiple lesions: 28.5/19.5%, grade 3: 34.8/39.9%, hormone receptor (HR) neg: 24.7/36.6%, HER-2 pos: 41.0/35.5%. Response rates for T4d, T4a-c, T1–3 were 8.4, 10.9, 17.5% (pCR, p=0.007), 36.7, 59.4, 72.6% (palpation after 2 cycles TAC, p<0.0001), 64.2, 62.3, 77.8% (palpation before surgery, p<0.0001), 52.6, 51.9, 67.4% (ultrasound before surgery, p<0.0001). BCT was performed in 12.6, 31.7, 69.5% (p<0.0001). Response after two cycles, negative HR content, young age, high grade, ductal type, but not tumor stage or size, were independent predictors for pCR in the total population. Conclusions: Inflammatory and cT4a-c breast carcinomas, compared to cT1–3 tumors, show less favorable tumor characteristics but a comparable pattern of response to TAC/NX. These patients do not need separate neoadjuvant trials. [Table: see text]
Meta-analysis of adjuvant trastuzumab for early breast cancer: Cardiotoxicity and brain metastases incidence
Authors: Cuppone F. , Bria E. , Giannarelli D. , Nisticò C. , Sperduti I. , Carlini P. , Milella M. , Ciccarese M. , Cognetti F. , Terzoli E. 
Published: March 2020

543 Background: The introduction of adjuvant trastuzumab (T) for early breast cancer overexpressing HER-2 has extraordinarily decreased the risk of both recurrence and death in 5 randomized clinical trials (RCTs). Nevertheless, the issue regarding the long-term safety profile of such drug is still open; in particular, questions remain about long-term cardiotoxicity, and specific pattern of relapse such as brain metastases (BM). In order to quantify the magnitude of these 2 risks, together with the survival outcome, a literature-based meta-analysis was performed. Methods: All phase III trials were considered eligible. A literature-based meta-analysis was accomplished, and event-based relative risk ratios (RR) with 95% confidence interval (CI) were derived. A fixed- and a random-effect model according to the inverse variance and the Mantel-Haenzel method were applied. Heterogeneity test was applied as well. Absolute differences (AD) and the number of patients needed to treat or to harm (NNT/NNH) were calculated. Primary end-points were: 1) chronic heart failure grade III-IV rate (CHF), 2) 10% reduction of L-FEV rate (L-FEV) and 3) BM rate. In order to quantify the magnitude of the significant benefit already found in the original RCTs, secondary end-points were: 1) disease-free survival (DFS) and 2) overall survival (OS). Results: Five RCTs were gathered (11,187 patients); at an average 2-yrs follow-up, all data were available for the cardiotoxicity and outcome end-points, while 3 RCTs reported results for BM analysis (6,738 patients). Conclusions: The overall outcome stresses that trastuzumab is likely to be one of the most important discovery in clinical oncology. Nevertheless, the biological activity of trastuzumab needs to be investigated more extensively to explore both long-term safety and specific relapse pattern. [Table: see text] No significant financial relationships to disclose.
Adjuvant external beam radiotherapy (EBRT) in the treatment of endometrial cancer: Results of the randomised MRC ASTEC and NCIC CTG EN.5 trial
Authors: Orton J. , Blake P. 
Published: March 2020

5504 Background: Patients with stage I endometrial cancer at high risk of relapse generally receive adjuvant EBRT following surgery, despite lack of evidence that radiotherapy improves overall survival (OS). ASTEC/EN.5 was designed to investigate whether OS is improved by adjuvant EBRT. An important secondary outcome was pelvic recurrence-free survival. Methods: Patients were randomised to receive immediate EBRT (with linear accelerator delivering 40–46Gy in 20–25 fractions to pelvis) or no EBRT until clinically indicated. Vault brachytherapy (4Gy in 2 fractions (HDR) or 15Gy (LDR)) could be used regardless of EBRT allocation. Centers were required to specify in advance whether brachytherapy would be offered to all patients or to none. The study was powered both to 1) detect a 9–10% absolute improvement in 5-year OS with adjuvant EBRT; and 2) reliably exclude an absolute 5% difference in 5-year OS when combined with other major studies (PORTEC and GOG 99). Results: Between Oct 1996 to Apr 2005, 906 patients (452 EBRT, 454 no EBRT) were randomised internationally. Pre-treatment characteristics were well balanced: median age 66 years; 98% of women WHO PS 0–1; 30% with lymph nodes removed at surgery; 84% endometrioid histology; depth of invasion to endometrium only, inner half and outer half of myometrium 3%, 20% and 77%, respectively; degree of differentiation to grade 1, 2, and 3 26%, 42%, and 31%, respectively. 92% patients in EBRT arm received immediate treatment, 90% receiving all protocol specified treatment. 2% patients in no EBRT arm received immediate EBRT. Brachytherapy was given to 52% patients in both arms. Morbidity was higher in EBRT arm, 56% compared with 24% in no EBRT arm reporting complications of treatment. Grade 3 or higher toxicity was rare. With a median follow-up of 46 months at the time of analysis, 117(13%) have died and 136(17%) have recurred or died. 130 deaths are required to detect a 10% difference in 5-year OS with 5% significance level and 90% power and this will be achieved by April 2007. Conclusions: Compliance was high. Serious complications were rare. The ASTEC/EN.5 trial alone and in combination with PORTEC and GOG99 will answer the question of the benefit of post-operative adjuvant EBRT in patients with endometrial cancer. No significant financial relationships to disclose.
Results from a phase II randomized, placebo-controlled, double-blind trial suggest improved PFS with the addition of pertuzumab to gemcitabine in patients with platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer
Authors: Makhija S. , Glenn D. , Ueland F. , Gold M. , Dizon D. , Paton V. , Birkner M. , Lin C. , Derynck M. , Matulonis U. 
Published: March 2020

5507 Background: Pertuzumab (P) is a humanized monoclonal antibody that blocks the ability of HER2 to heterodimerize with other HER/ErbB receptors. As a single agent, P has demonstrated clinical activity in relapsed/refractory epithelial ovarian cancer (EOC). Since platinum-resistant (CDDP-R) EOC remains a difficult disease to treat, this phase II study was conducted to determine if addition of P to gemcitabine (G) would improve results. Methods: Patients with CDDP-R EOC (including ovarian, fallopian tube, or primary peritoneal cancer) who had received up to one prior treatment for CDDP-R disease were randomized to Gem 800 mg/m2 on D1, 8 of a 21-day cycle ± P or placebo (pl). P was given as an 840 mg initial dose followed by 420mg IV every 3 weeks. Tumor response was assessed by RECIST every 6 weeks using GOG criteria. The primary endpoint was progression free survival (PFS). Results: One hundred thirty patients (n = 65 each treatment cohort) were treated. Clinical characteristics were balanced between the treatment groups. Pts received a median of 2 prior regimens (range 1–6) for EOC. Based on 83 events, the adjusted hazard ratio for PFS was 0.67 (95% CI: 0.43–1.02), p =0.06 in favor of P+Gem. The median PFS was 3.0 months (0–8.7 months) vs. 2.6 months (0–9+ months), and the PFS rate at 4 months was 49% vs. 34% in the P+Gem and Gem/pl arms, respectively. The most common AEs increased in the P-treated pts were fatigue, nausea, diarrhea, back pain, Gr 3–4 neutropenia, rash, headache, stomatitis, epistaxis, and rhinorrhea. Clinically significant CHF was reported in one patient in the pertuzumab cohort. There was no imbalance in the LVEF results between treatment arms. One patient who received pertuzumab + gemcitabine experienced an adverse event that resulted in death (hemolytic-uremic syndrome). Conclusions: These data suggest that pertuzumab may add activity to gemcitabine as reflected by improvements in PFS in patients with CDDP-R ovarian, primary peritoneal, or fallopian tube cancer. Survival data will be presented at ASCO. No significant financial relationships to disclose.
A prospective multi-center ovarian cancer screening study in women at increased risk
Authors: Skates S. J. , Drescher C. W. , Isaacs C. , Schildkraut J. M. , Armstrong D. K. , Buys S. S. , Brewster W. R. , Daly M. B. , Finkelstein D. M. , Lu K. H. ,   ROCA Screening Study Group
Published: March 2020

5510 Background: No proven ovarian cancer (OC) screening strategy exists for women who are at increased risk for the disease. A risk of ovarian cancer algorithm (ROCA) using serial CA125 values has previously shown greater positive predictive value (PPV) and sensitivity than a single CA125 in screening women at general population risk. We hypothesized that using ROCA would yield a reasonable PPV for ovarian cancer screening in a cohort at increased risk. Methods: Between 7/2001 and 9/2006, 25 sites (14 Cancer Genetics Network, 3 ovarian SPOREs, 1 EDRN, 7 others) prospectively enrolled patients. Inclusion criteria included: among self, 1° or 2° relatives in same lineage either (i) BRCA1/2 mutation, or (ii) two of OC or early onset (age = 50) breast cancer (BC), or (iii) Ashkenazi ethnicity and 1 of OC or BC. A previous diagnosis of OC excluded subjects. Subjects underwent CA125 every 3 months and the risk of having ovarian cancer based on the CA125 profile was recalculated after each test. ROCA referred subjects with risk > 1% to ultrasound (US), and risk > 10% additionally to a gynecologic oncologist. Objectives included PPV for study indicated surgery, sensitivity, and compliance. Sample size was chosen to observe 8 OC endpoints with a power of 80% to rule out PPV = 10% if the true PPV = 20%. Results: 2,343 high risk women enrolled, with 6,284 women years of screening and 19,549 CA125s obtained. There were 628 (10%/yr) referrals to US with 414 US performed. 38 women underwent study indicated surgeries. 9 OCs were identified during screening, 3 were prevalent (1 early, 2 late stage), and 6 were incident (5/6 = 83% early, 1 late). 3 of the 6 incident cases were found on prophylatic oophorectomy in early stage. ROCA detected 2 in early stage of remaining 3 incident cases, and 3 of 3 prevalent cases. The PPV was 5/38 = 13% (95% CI 4.4%, 28%) and sensitivity was 5/6 = 83%, CI (36%, 99%). There was high compliance with CA125 testing throughout study, with 84%, 85%, 85%, 82% subjects returning within 1 month of schedule for first 4 tests. Conclusions: Frequent CA125 testing using ROCA results in an acceptable PPV and high compliance in a cohort of women at increased risk for OC. A definitive screening study (= 30 incident cases) using ROCA with serial CA125 and possibly additional markers is required to define sensitivity for early stage OC. [Table: see text]
STK15 F31I polymorphisms and uterine cancer risk: A case-control analysis
Authors: Milam M. R. , Gu J. , Yang H. , Celestino J. , Wu W. , Horwitz I. , Lacour R. A. , Westin S. N. , Gershenson D. M. , Wu X. , Lu K. H. 
Published: March 2020

5511 Background: STK15 is a serine threonine kinase which assists chromosomal separation and mitotic spindle stability through interaction with the centrosome during mitosis. STK15 polymorphisms have been associated with an increased risk for breast cancer in several case-control studies. We hypothesized that STK15 polymorphisms might modulate risk of uterine cancer. Methods: Uterine cancer patients treated at M. D. Anderson Cancer Center were identified from the tumor bank database from January 1, 2000 to June 30, 2006. Two common STK15 single nucleotide polymorphisms (SNPs), F31I (T/A) and V57I (G/A), were genotyped in patients with uterine cancer and in a control population matched for age, race, and smoking status. Odds ratios (OR) and 95% confidence intervals (CI) were obtained using unconditional logistic regression analysis. Results: A total of 193 women with uterine cancer and 218 controls were genotyped for both SNPs. After adjustment for age, race, and smoking status for the F31I SNP, the homozygous variant genotype (AA) was associated with a significantly increased uterine cancer risk (OR 10.2; 95% CI 2.23–46.5). Individuals with the heterozygous genotype (TA) and a history of tobacco use also exhibited an increased risk for uterine cancer (OR 2.63; 95% CI 1.20–5.76). For the V57I SNP, neither the homozygous (AA) nor the heterozygous (GA) variant genotypes were associated with significantly altered risk for uterine cancer (OR 0.76; 95% CI 0.18–3.25 and OR 0.88; 95% CI 0.52–1.49). Conclusions: Our study demonstrates that STK15 F31I SNP is associated with an increased risk for uterine cancer. Confirmation of this pilot study is needed in a larger case-control population to evaluate this genetic variant with other known risk factors for uterine cancer. No significant financial relationships to disclose.
Survival in advanced-stage ovarian cancer patients with non-Ashkenazi Jewish BRCA mutations
Authors: Lacour R. A. , Westin S. N. , Daniels M. S. , Milam M. R. , Sun C. C. , Urbauer D. L. , Ramirez P. T. , Bodurka D. C. , Gershenson D. M. , Lu K. H. 
Published: March 2020

5514 Background: Previous studies have shown a survival advantage in ovarian cancer patients with Ashkenazi-Jewish BRCA founder mutations compared to sporadic ovarian cancer patients. The purpose of this study is to determine if this association exists in ovarian cancer patients with non- Ashkenazi Jewish (non-AJ) BRCA1 or BRCA2 mutations. Methods: Patients with stage III or IV ovarian, fallopian tube, or primary peritoneal cancer and a BRCA1 or BRCA2 mutation, seen for genetic testing between January 1996 and October 2006, were identified from the institutional and genetics databases. Medical records were reviewed for clinical factors including response to initial chemotherapy. Response is defined as no clinical evidence of disease with normalization of serum CA-125 and no radiographic evidence of disease or a negative second-look surgery. Patients with sporadic ovarian cancer, without a family history of breast or ovarian cancer, were compared to similar cases, matched by age, stage, and year of diagnosis. Progression-free and overall survival were calculated by the method of Kaplan-Meier. Chi-square tests and univariate logistic regression were also used in the data analysis. Results: Thirty-nine advanced-stage ovarian cancer patients with non-AJ BRCA mutations and 47 matched, advanced-stage sporadic ovarian cancer patients have been analyzed. Compared to patients with sporadic ovarian cancer, non-AJ BRCA mutation carriers had a longer progression-free survival (PFS, 32.4 mos. vs. 22.1 mos., p = 0.0303) and overall survival (OS, 101.4 mos. vs. 51.3 mos., p < 0.001). Similarly, 72% of the non-AJ BRCA mutation carriers had a complete response to initial treatment, compared to 45% of the sporadic ovarian cancer patients (p = 0.01). The odds of complete response to initial treatment were 3.2 times greater in the non-AJ BRCA group than in the sporadic group (OR 3.2; 95% CI 1.27 - 8.15). Conclusions: This study demonstrates a significant survival advantage in advanced-stage ovarian cancer patients with non-AJ BRCA mutations when compared to similar patients with sporadic ovarian cancer. Response to initial treatment appears to impact this improved survival. No significant financial relationships to disclose.
Durable clinical responses in patients (pts) with ovarian carcinoma treated on a phase II trial of autologous dendritic cells (DC) pulsed with MUC1
Authors: Mitchell P. , Loveland B. E. , Quinn M. A. , Grant P. T. , Allen D. G. , Jobling T. W. , White S. C. , Wall D. M. , Zhao A. , Karanikas V. 
Published: March 2020

5515 Background: Mucin 1 (MUC1) is a glycoprotein highly expressed by ovarian carcinoma and is thus a potential antigen for immunotherapy. Following successful phase I results (Loveland et al. Clin Can Res 2006; 12:869), using DC pulsed with mannan-MUC1 fusion protein (DC-MFP), we report a phase II trial in similarly treated pts with ovarian carcinoma. Methods: Eligibility: incurable disease; age = 18 yrs; PS 0–2; no autoimmune disorders; rising CA125 levels (= 25% in 1 mth, confirmed). The primary endpoint was CA125 response (major = 50%, minor = 25%, each confirmed at = 4 wk) or stabilisation (= 3 mths). PBMC were collected by leukapheresis, cultured with IL-4 and GM-CSF to generate DC, and pulsed with MFP on d5. DC were reinjected on d6 as 8 i.d. injections (each 5x106), given 4-weekly × 3, then 10- weekly to 12 mths. Excess cells were cryopreserved for subsequent injections. Results: 28 pts were recruited, with all evaluable for toxicity and 21 for efficacy (received = 3 vaccinations). Characteristics were: serous histology 24 (86%) pts; median age 58 yrs (34–78); PS 0–1 27 (96%) pts; prior systemic therapy (all pts platinum-treated) 1 line 5 pts, 2 line 4 pts, 3 line 10 pts, = 4 lines 9 pts. Leukapheresis was generally required only 6-monthly. Following ex vivo culture, the proportion of CD86+ cells ranged from 40 - 85%. There was no grade = 3 therapy-related toxicity. Of 21 pts, 4 (19%) showed CA125 response or stabilisation. 2 pts had major response: 1 pt with 4 previous lines of systemic therapy (DC-MFP response duration 12+ mths) and 1 pt treated second line (duration 14 mths). One pt had stable disease of 7 mths duration which included 10 wks classified as minor response and one pt, treated fifth-line, had stable disease for 5 mths. An additional pt, treated fourth-line, had >25% CA125 reduction which was not confirmed by repeat CA125. CT scan results were generally concordant with CA125 status. No relationship was seen between clinical benefit and HLA type. 88% of tumours were MUC1+ on IHC. Conclusions: Study treatment was well tolerated and acceptable to pts. There was clear evidence of clinical benefit, including pts who were heavily pre-treated. This approach warrants further study in ovarian carcinoma. Supported by grants from PrimaBiomed Ltd. No significant financial relationships to disclose.
Safety of maintenance bevacizumab after first-line chemotherapy for advanced ovarian and müllerian cancers
Authors: Campos S. M. , Dizon D. S. , Cannistra S. A. , Roche M. , Krasner C. N. , Berlin S. T. , Horowitz N. S. , DiSilvestro P. , Matulonis U. A. , Penson R. T. 
Published: March 2020

5517 Background: Bevacizumab is a recombinant humanized monoclonal antibody that neutralizes VEGF, but is associated with arterial complications and GI perforations in patients with advanced ovarian cancer. Maintenance antiangiogenic therapy is an attractive strategy for patients after first line therapy. However, no data exist on the safety of maintenance bevacizumab in this setting. Methods: An open label phase II clinical trial of carboplatin, paclitaxel and bevacizumab (CPB) in newly diagnosed patients =ECOG 2, with chemotherapy naïve, stage =IC, epithelial müllerian tumors. Patients receive carboplatin AUC 5 IV, paclitaxel 175 mg/m2 IV, and bevacizumab 15 mg/kg IV for 6–8 cycles D1 Q21. Bevacizumab is omitted in the first cycle, and continued as single agent for one year. Results: 58 patients are evaluable. Median age is 58 (18–77), and 39(67%) were ECOG 1. 43(74%) have ovarian, 8(14%) uterine papillary serous (UPSC) tumors, 4(7%) peritoneal, and 3(5%) fallopian tube cancers. 38(65%) were serous, 8(14%) MMMT, 4(7%) clear cell, and 3(5%) endometrioid cancers (5(9%) mixed/other). 36(62%) were stage III and 11(19%) stage IV. Surgery was optimal in 45(80%) patients. 50 patients have completed chemotherapy, associated with 2 PEs, and 2 GI perforations, all occurring during the induction chemotherapy phase of treatment. 43 patients have received 360 cycles of maintenance therapy with mild toxicity. 6(14%) have come off for PD, 4(9%) for toxicity (inc. 1 nasal perforation), 4 withdrew consent, and 3 patients asymptomatic, continue despite a rising CA125. During maintenance there has been no grade IV toxicity, and 13 grade III toxicities (musculoskeletal pain (5), dyspnea, hyperglycemia, hypertension (1 grade III, 4 grade II), infection, lymphopenia, thrombocytopenia, proteinuria, syncope). Radiographic responses were documented in 21 of 28 (75%: CR 11, PR 10). Median PFS is 11(1–21) months at 13 months median FU. Conclusion: Maintenance bevacizumab is feasible and well tolerated with mild myalgias, and hypertension common but treatable side effects. No significant financial relationships to disclose.