bluuebunny/crossref_metadata_2025_split huggingface dataset:
Results from a phase II study to assess the efficacy and tolerability of fulvestrant 250 mg/month as treatment of recurrent or metastatic endometrial carcinoma
Authors: Emons G. , Guenthert A. , Thiel F. , Camara O. , Strauss H. , Breitbach G. , Koelbl H. , Reimer T. , Finas D. , Rensing K. 
Published: August 2020

5532 Background: Fulvestrant (F) is a pure anti-estrogen with no agonistic action and no known adverse effects on the endometrium. This may be an advantage over tamoxifen, which has been successfully used in the treatment of hormone-receptor (HR) positive recurrent or metastatic endometrial carcinoma. Methods: This was an open label single-arm multicentre phase II study (AGO-Uterus 5) in patients with recurrent or metastatic endometrial carcinoma and measurable disease (RECIST). Pts. received monthly 250 mg F i.m. injections. The primary objective was clinical response after 3 injections, measured 4 weeks after injection 3 (ITT-pop.). Safety and tolerability were secondary endpoints. Results: Between March 2003 and May 2006, 35 pts. were included. Mean age was 70 years (range 45–83), first diagnosis was a mean 2.6 years ago, diagnosis of recurrence 10.2 months ago. 25 pts. (73.5%) had a FIGO 4B; 24 pts. (71%) had endometrioid cancer, 5 (15%) serous and 5 other carcinoma. All pts. had a positive ER and/or PgR status. 1 pt. had received no surgery for her disease; 21 pts. (61.8%) had prior radiotherapy; 13 pts. (38.2%) chemotherapy. 26 pts. were assessed as planned (ITT); 5 pts. received fewer than 3 injections, 4 pts. were not seen 4 weeks after inj. 3. Response to F was PR in 5 pts. (19.2%) and SD in 8 pts. (30.8%), adding up to a 50% disease control rate. 13 pts. had PD. Tolerability was good, no previously unknown side effects occurred. Conclusions: F showed encouraging response rates in our patient collective and was well tolerated. Further studies are warranted with F in HR pos. endometrial carcinoma. This study was supported by AstraZeneca. F is licensed for treatment of ER+, advanced breast cancer after an antioestrogen in postmenopausal women. [Table: see text]
Microsatellite instability and loss of PTEN expression in early versus late-stage endometrial cancer: Results from studies of the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG)
Authors: Mackay H. , Gallinger S. , Tsao M. , McLachlin C. M. , Kieser K. , Eisenhauer E. , Tu D. , Oza A. 
Published: August 2020

5534 Background: Microsatellite instability (MSI+) and inactivation of the tumor suppressor gene PTEN are implicated in the development of endometrial cancer (EC). The aim of this study was to compare the prognostic value of MSI and PTEN in 2 patient (pt) populations, early stage vs. advanced/recurrent disease. Methods: Archival paraffin embedded tumor from pts with EC enrolled in closed NCIC-CTG studies: stage I/II (EN5) and advanced/recurrent disease(IND 126, 148 and 160) were examined for MSI (BAT 25/26) and for PTEN expression (immunohistochemistry). PTEN and MSI status were correlated with clinicopathologic features and outcome from NCIC-CTG trial databases. Results: 188 pt samples (97 stage I/II;91 advanced/recurrent disease) were examined. Results are available for PTEN in 129 pts and MSI in 166 pts. Overall, 55% were PTEN negative (-) and 19.3% MSI+. 33 (56.9%) pts were PTEN - in EN5 vs. 38 pts (53.5%) IND studies (p = 0.73). Overall, no association was seen between PTEN or MSI status and age, performance status (PS), tumor grade or histology. In univariate analysis, there was a trend towards improved survival (S) in pts with PTEN - EC (HR = 0.61; 95% CI, 0.36 -1.04, p = 0.07), weaker in multivariate analysis (HR = 0.56; 95% CI, 0.26–1.18 p = 0.12). In EN5, PTEN status was not associated with S in uni-or multivariate analyses. In the IND studies there was a trend towards improved S in univariate analysis (HR = 0.57; 95% CI, 0.32–1.06 p = 0.07). More pts were MSI+ in EN5, 23 (27.4%) vs. IND studies, 9 (11%) p = 0.01. In EN5, microsatellite stable (MSS) tumors were associated with a better prognosis in both univariate (HR = 0.18; 95% CI, 0.06–0.51, p < 0.0001) and multivariate analysis (HR = 0.16; 95% CI, 0.05 to 0.5, p < 0.0001). There was no difference in S between pts with MSS vs. MSI+ tumors overall, or in the IND studies. in uni- or multivariate analyses. There was no correlation between MSI and PTEN status overall or in either group of pts. Conclusions: MSI+ tumors are more common, and are associated with a worse prognosis, in early stage EC. There is a trend towards improved S for pts with PTEN- advanced EC. There is no association between PTEN and MSI status. No significant financial relationships to disclose.
A phase II study of intravenous (IV) and intraperitoneal (IP) paclitaxel, IP cisplatin, and IV bevacizumab as first-line chemotherapy for optimal stage II or III ovarian, primary peritoneal, and fallopian tube cancer
Authors: Konner J. A. , Grabon D. , Pezzulli S. , Iasonos A. , Sabbatini P. , Hensley M. , Bell-McGuinn K. , Tew W. , Spriggs D. , Aghajanian C. 
Published: August 2020

5539 Background: IP cisplatin (Cis) plus IV/IP paclitaxel (Tax) is a standard therapy for optimally debulked ovarian cancer. Bevacizumab (Bev) is a recombinant humanized IgG1 monoclonal antibody directed against vascular endothelial growth factor. Activity of Bev in recurrent ovarian cancer has been reported in phase II trials. In this study IP Cis and IV/IP Tax are combined with IV Bev as front-line therapy. Methods: Patients with optimal (<1 cm residual), FIGO stage II or III, epithelial ovarian, fallopian tube, or peritoneal cancer, acceptable organ function, and KPS ≥ 70% are eligible. Patients receive 6 cycles of chemotherapy plus Bev: Tax 135 mg/m2 IV over 3 hours on Day 1, Cis 75 mg/m2 IP on Day 2, Tax 60 mg/m2 IP on Day 8, Bev 15 mg/kg IV on Day 1 (starting cycle 2). Bev is continued every 3 weeks for 17 treatments after chemotherapy is complete. This study will enroll 41 patients. The primary endpoint is safety and tolerability, determined by whether at least 60% of patients complete the prescribed 6 cycles of cytotoxic chemotherapy without unacceptable toxicity. Results: Thirty-nine women [median age 56 (40–69)] have been treated on study: 26 (67%) completed 6 IV/IP cycles; 5 (13%) are receiving ongoing IV/IP treatment; 4 (10%) experienced IP port malfunction (3 finished 5 IV/IP cycles, 1 came off study for port revision); 3 (8%) switched from IP Cis to IV carboplatin due to grade 3 nephrotoxicity in cycle 1 (n = 2) or grade 3 hypertension in cycle 6 (n = 1); and 1 (2.5%) patient died following rectosigmoid anastomotic dehiscence during cycle 4. Grade 3/4 treatment-related toxicities include hypertension (10%), vasovagal events (10%), neutropenia (26%), nausea/vomiting (10%), and hypomagnesemia (8%). There were 3 occurrences of grade 3 abdominal pain (8%); and 3 adhesion-related grade 3 small bowel obstructions (8%), during cycles 3, 9, and 15, respectively. Conclusions: The addition of Bev to this IV/IP regimen appears to be feasible. Bev may increase the risk of small bowel obstruction/perforation in these patients. Enrollment continues and updated results will be presented. [Table: see text]
Effects of weekly bevacizumab and pegylated liposomal doxorubicin in heavily pretreated patients with recurrent or progressed ovarian cancer
Authors: Kikuchi Y. , Kouta H. , Kikuchi R. , Takano M. , Kita T. , Kudoh K. , Aoki D. , Sugiyama T. , Isonishi S. 
Published: August 2020

5547 Background: Vascular endothelial growth factor (VEGF) plays a central role in tumor angiogenesis and is regarded a promising therapeutic target. Bevacizumab (A) has significant antitumor activity in combination with cytotoxic agents. Currently, pegylated liposomal doxorubicin (D) is provided as one of the standard treatment options in recurrent ovarian cancer. Thus, we attempted to determine effects in combination of A and D for heavily pretreated patients with recurrent or progressed ovarian cancer. Methods: Twenty-two patients with heavily pretreated (more than one regimen or more than 6 cycles by paclitaxerl and carboplatin) received at least more than 3 cycles of weekly A-D consisting of A: 2 mg/kg and D: 10 mg/m2 (3 weeks, one week rest). The primary endpoint was response according to CA 125 and response evaluation criteria in solid tumor (RECIST) criteria. Results: Of 22 patients evaluable for CA 125 response, 7 (32%) had a response (decrease of >50%), and 8 (36%) patients had not progressed (doubling of CA 125) following 6 months on treatment. In RECIST evaluation, 2 (9%) patients had complete remission (CR) and 6 (27%) had partial remission (PR), resulting in 55% clinical benefit rate (CBR). Progression free interval (PFI) showed more than 6 months. Any hematological adverse effect was not observed in the present study. Gastrointestinal perforation was observed in only one case and was conservatively treated. Although nasal bleeding was frequently observed, no treatment was required. A induced hypertension was also observed and manageable. Hand-foot syndrome seemed due to D was seen in 3 of 22 patients and treatment was required in only one case. Conclusions: B seemed to enhance effect of D. This is the first study of weekly A-D in heavily pretreated ovarian cancer patients. Weekly A-D warrants further clinical study in such clinical settings. No significant financial relationships to disclose.
Correlation of CA-125 and RECIST evaluation in recurrent ovarian cancer (ROC): Results from a randomized phase III study of trabectedin (T) with pegylated liposomal doxorubicin (PLD) versus PLD alone
Authors: Herzog T. J. , Vermorken J. B. , Pujade-Lauraine E. , Li J. , Bayever E. , Gomez J. , Yovine A. , Monk B. J. 
Published: August 2020

5550 Background: OVA-301, an open-label, multicenter, randomized phase III study comparing the combination of T and PLD to PLD alone in 672 ovarian cancer patients, showed significant prolongation in Progression-Free Survival (PFS) and higher Objective Response (OR) in the combination arm (T-PLD) by three separate assessments, investigator assessment (IA), independent radiology (IR) and oncology review (IO). The purpose of this analysis is to examine: 1) the impact of early changes in CA-125 over the subsequent best OR by RECIST; 2) the concordance between best OR determined by CA-125 and RECIST; 3) the value of CA-125 to predict radiological response. Methods: Tumor assessments by imaging and CA-125 were performed at baseline, and every 8 weeks during study in both arms. Radiological tumor assessment, regardless of CA-125 changes, determined the study conduct. Early CA-125 changes were those assessed at the first and second evaluation. Analyses were based on “all randomized patients.” Results: Response rate by RECIST (IR)/CA-125 was 28%/48% for T-PLD vs. 19%/33% for PLD. The association between CA-125 and RECIST response was stronger for IA relative to IR/IO, with 79% concordance for both arms, 65% overall positive predictive value (PPV) and 89% negative predictive value (NPV) for IA and 74%/75% concordance, 46%/49% PPV and 93%/92% NPV for IR/IO. Early CA-125 changes were assessed in 514 patients. Early ≥25% CA-125 decreases in the first/second evaluation occurred in 85%/95% of RECIST responders in the T-PLD arm and in 81/82% responders treated with PLD. Conclusions: The predictive value of CA-125 response was high and similar in both arms. The addition of T to PLD resulted in superior efficacy in this patient population as assessed by IA, IR and IO, with a favorable trend for CA-125 response assessment. RECIST response was preceded by a significant CA-125 decrease in a high proportion of patients. [Table: see text]
Circulating tumor cells (CTC) in a study of relapsed/recurrent advanced ovarian cancer: An exploratory analysis in the ova-301 phase III study of pegylated liposomal doxorubicin (PLD) compared with trabectedin and PLD
Authors: Poveda A. , Kaye S. B. , McCormack R. T. , Wang S. , Ricci D. , Broderick E. , Parekh T. , Lebedinsky C. , Tecero J. C. , Monk B. J. 
Published: August 2020

5551 Background: Circulating tumor cells (CTC) have demonstrated predictive and prognostic value among patients with metastatic breast, colorectal, and prostate cancer. In a phase III study of pegylated liposomal doxorubicin (PLD) with trabectedin (T) vs PLD for relapsed ovarian cancer, we assessed the affect of CTCs on progression free survival, (PFS) and overall survival (OS). Methods: CTCs were isolated from peripheral blood (10 mLs) using the CellSearch system and reagents (Veridex). A CTC is defined as EpCAM+, cytokeratin+, CD45-, and is positive for the nuclear stain DAPI. The normal reference range for CellSearch is < 2 CTC/7.5 mLs of blood. Hazard ratios adjusted for known prognostic factors were estimated by Cox regression. Results: 216 subjects had baseline CTC measurements of which 111 (51.4%) were randomized to the PLD+T arm; 143/216 patients (66.2%) were platinum sensitive. Thirty-one/216 patients (14.4%) had 2 or more CTCs detected prior to the start of therapy (range 2–566). Univariate Cox regression analyses indicated that patient's > 2 CTCs prior to therapy have 1.89 (p = 0.003) and 2.06 (p = 0.003) fold higher risk for progression and death respectively. Multivariate analyses that include baseline CTC, baseline CA125, platinum sensitivity status, largest diameter lesion, number of tumor lesions, ECOG PS, age, tumor histology, tumor grade and prior taxane show that patients with elevated baseline CTC have 1.58 (p = 0.058) and 1.54 (p = 0.096) fold higher risk for progression and death respectively. Conclusions: Results from this study indicate that although CTC detection in blood from relapsed recurrent ovarian cancer patients is relatively low, elevated numbers of CTCs imparts an unfavorable prognosis for patients. Multivariate analysis indicates that CTCs have prognostic value that is independent of established factors and thus provides a clinically useful tool for assessing prognosis in this difficult to treat patient population. [Table: see text]
Prediction of nutritional status and intestinal tumor involvement in patients with primary or recurrent ovarian cancer: Results of a prospective study
Authors: Kuhberg M. , Skowronek P. , Chen F. , Oskay-Oezcelik G. , Oskay-Oezcelik G. , Lichtenegger W. , Lichtenegger W. , Sehouli J. 
Published: August 2020

5570 Background: Global malnutrition is widespread among patients with ovarian cancer. The objective of this study was to investigate the influence of the nutritional status on the clinical outcome of patients with primary or recurrent ovarian and peritoneal cancer. Methods: In a two-year-period (January 2007 - December 2008) 152 consecutive patients were analysed. 79 (52%) of them had primary and 73 (48%) recurrent disease. At the time of admission for surgical therapy, the body composition was analysed with Bioelectrical Impedance Analysis (BIA) using phase angle alpha and ratio of extra-cellular mass and body cell mass (ECM/BCM). Serum protein parameters were registered. The risk of malnutrition was estimated by Nutritional Risk Score (NRS). During operation a standardised and validated tumor documentation tool (IMO) was performed. Nutritional parameters were correlated with IMO-parameters. Results: The median age of patients was 56 years (range 48–66) with median BMI 24.4 kg/m2 (range 21.8–27.3). In 23% primary and 14% recurrent cases a high nutritional risk was classified (NRS≥3). These patients had significantly lower serum albumin, pre-albumin and transferrin levels compared to patients with NRS<3 (p < 0.05). FIGO stage and NRS correlated negatively with phase angle alpha and positively with ECM/BCM in patients with primary diagnosis (p < 0.05). Patients with primary or recurrent disease who required surgical resection of small or large intestine, phase angle alpha and serum albumin level were significantly lower than in patients with no intestinal involvement (p < 0.05). Conclusions: Independent of tumor stage, the preoperative evaluation of BIA, especially phase angle α, is a valid method to predict surgical outcome in patients with ovarian and peritoneal cancer. No significant financial relationships to disclose.
Validation of a novel staging system for breast cancer patients treated with neoadjuvant chemotherapy
Authors: Mittendorf E. A. , Tucker S. L. , Jeruss J. S. , Gonzalez-Angulo A. M. , Buchholz T. A. , Sahin A. A. , Cormier J. N. , Buzdar A. U. , Hortobagyi G. N. , Hunt K. K. 
Published: August 2020

558 Background: We previously described a novel staging system to assess patient prognosis after neoadjuvant chemotherapy based on pretreatment clinical stage (CS), post-treatment pathologic stage (PS), estrogen receptor (E) status and grade (G). This CPS+EG staging system was determined by points assigned for each variable and allowed for better determination of breast cancer specific survival than either CS or PS alone. The current study was undertaken to validate this staging system in a more contemporary cohort of patients. Methods: A prospectively collected database of patients treated with neoadjuvant chemotherapy from 2003 to 2005 identified 804 eligible patients for analysis. Because determination of the CPS+EG staging system predated the use of neoadjuvant trastuzumab therapy, patients receiving neoadjuvant trastuzumab were excluded from the validation cohort. Clinicopathologic characteristics, treatment regimens and patient outcomes were assessed. Patient outcomes were stratified according to their CPS+EG score. Results: Median follow-up time was 3.4 years (range 0.3–5.9 years). The 5-year disease specific survival (DSS) rate for the entire cohort was 77% (95% CI: 72–82). The table summarizes 5-year DSS rates for each CPS+EG score. The pattern of prediction determined in the initial cohort was again seen in the validation cohort. Application of the staging system facilitated separation of patients into more refined subgroups by outcome than the current AJCC staging system applied to either presenting clinical stage or final pathologic stage. Conclusions: This study validates our previously published CPS+EG staging system. We suggest that the AJCC staging system should be revised to incorporate biologic markers and response to treatment for patients receiving neoadjuvant chemotherapy. As targeted agents are being increasingly employed in treatment regimens, future work will focus on further refinement of the staging system with additional biologic markers. [Table: see text] No significant financial relationships to disclose.
Factors associated with regression of cervical dysplasia in adolescents: A retrospective study
Authors: Chen C. , Campbell F. , Patruno J. , Kimmel S. , Boulay R. , Meyers C. , Martino M. 
Published: August 2020

5582 Background: Sexually active adolescents have high rates of infection with human papilloma virus (HPV) and abnormal pap smears. They are considered a special population as they are likely to regress to normal cytology. The aim of our study was to identify factors associated with regression of cervical dysplasia in adolescents. Methods: We identified adolescent patients (aged 12–21 years) who had abnormal pap smears at the Center for Women's Medicine at Lehigh Valley Hospital in Allentown, PA, by CPT code from a database between Jan 2004 and Dec 2006. A chart review was performed to capture demographic data, cytology, smoking history, number of sexual partners, parity, race, contraceptive choice, use of barrier contraception. Chi-square analysis with logistic regression and multivariate analysis were used to identify factors associated with regression of cervical dysplasia. Results: Two-hundred two patients were identified. Mean age was 18.84 years (14–22 years). One hundred twenty-two (57.8%) were Hispanic, 71 (33.6%) Caucasian, and 16 (7.6%) Black. Fifty-two (24.6%) were pregnant at the time of diagnosis. Seventy-six (36%) were smokers. There were 125 (61.9%) cases of ASCUS, 33.7% (68 cases) LGSIL and 4.5% (9 cases) HGSIL on initial pap smear. One hundred eighteen (55.9%) patients had colposcopy, and of these, 32 (15.2%) had surgical intervention. Follow-up demonstrated that 72 (57.6%) patients had disease regression, 24 (19.2%) persistence and 29 (23.2%) progression. On multivariate analysis, patients who did not smoke were significantly more likely to show regression of cervical dysplasia on pap smear than women who smoked (OR 2.17, 95% CI 1.03–4.55, p = 0.039). Other factors were not statistically significant in predicting regression of cervical dysplasia. Conclusions: Adolescents who smoke were more likely to have persistent cervical dysplasia than non-smoking adolescents, putting smokers at an increased risk of advanced disease. We suggest that this subset have follow-up at shorter intervals and be enrolled in a smoking cessation program. No significant financial relationships to disclose.
Evaluation of tumor-infiltrating lymphocytes (TIL) and tumor cell apoptosis as predictive markers for response to neoadjuvant chemotherapy in triple-negative breast cancer
Authors: Ono M. , Tsuda H. , Shimizu C. , Yamamoto S. , Shibata T. , Kouno T. , Tamura K. , Ando M. , Katsumata N. , KInoshita T. , Fujiwara Y. 
Published: August 2020

559 Background: Triple-negative breast cancer (TNBC) lacks the expression of estrogen receptor (ER), progesterone receptor (PgR) and HER-2. Pathological complete response (pCR) of TNBC to neoadjuvant chemotherapy (NAC) is correlated with excellent clinical outcome. We examined the value of histological parameters including tumor-infiltrating lymphocytes (TIL) and tumor cell apoptosis as surrogate markers for pCR in TNBC. Methods: Of 474 patients who received NAC and subsequent surgical therapy to stage II-III invasive breast carcinoma between 1999 and 2007, 102 (22%) had TNBC, and 92 core needle biopsy (CNB) specimens before NAC were available. We first immunohistochemically confirmed TNBC and basal-like subtype by current criteria for ER, PgR, and HER-2, cytokeratin (CK) 5/6, CK14, EGFR, and p53. All cases were TNBC, and 54 tumors (59%) were basal-like subtype defined as expression of at least one of CK5/6, CK14 and EGFR in >1% of cancer cells. Totally, 26 tumors (28%) showed pCR. Thirteen histopathological parameters were examined, and their correlation with pCR rate was tested. These parameters were also examined in resected tumor specimens from 21 non-pCR cases. Results: The pCR rate was significantly higher in the patients with tumors with TIL (24 of 68, 35%) than in those without (2 of 24, 8%, p = 0.01), and higher in tumors with high-score apoptosis (9 of 19, 47%) than in those with low-score apoptosis (17 of 73, 23%, p = 0.04). Tumors showing medullary features and p53-negative tended to show pCR more frequently (38% and 35%) than those with non-medullary features and with p53-positive (25% and 24%), but the differences were not significant. Of 21 non-pCR cases, TIL was consistently negative before and after NAC in 8, but TIL emerged after NAC in 13. The pCR rate did not differ significantly between the basal-like type (31%) and non-basal-like type (24%). Conclusions: TIL and the level of tumor cell apoptosis appeared predictive markers for response to NAC in TNBC. Patients’ host factors correlated with immune response appears play a substantial role in the response to NAC in TNBC. No significant financial relationships to disclose.