bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of docetaxel in metastatic, castration-resistant prostate cancer (mCRPC): Comparison with therapeutic standards in other solid tumors
Authors: Pappagallo G. L. , Spatafora S. , Bari M. , Sartori D. , Vinante O. 
Published: August 2020

5167 Background: Difference of opinion exists between urologists and oncologists as to what constitutes a beneficial survival advantage from a drug. Therefore, the aim of this analysis was to consider the efficacy of docetaxel (DOC) in the treatment of mCRPC as compared with the efficacy results previously observed in breast cancer (BC), non-small cell lung cancer (NSCLC), and colorectal cancer (CRC). Methods: A systematic review (Review Manager 5, Cochrane Collaboration, 2008) of the phase III studies which defined the new standard approaches in the 1st-line cytotoxic chemotherapy of metastatic disease for the above mentioned neoplasms was conducted. The relative efficacy of taxane combinations (TAX) in BC, cisplatin-based doublets (DDP) in NSCLC, 5FU/LV-oxaliplatin (FOLFOX) in CRC and DOC-based combinations in mCRPC were calculated. Efficacy parameters for the present analysis were: a) odds ratio for death (fixed method) and: b) NNT[odds ratio], e.g. the number of patients you need to treat to prevent one additional death, as compared with the control group; the NNT (odds ratio) is (1-(pc*(1-OR))/((1-pc)*pc*(1-OR)), where pc is the proportion of death events in the control arm and OR is the odds ratio for death. Results: BC (4 studies, 1313 patients), TAX vs non TAX: OR 0.84 (95% CL 0.66 1.07), NNT (odds ratio) at 5 years = 28. NSCLC (9 studies, 4671 patients), DDP vs non DDP: OR 0.83 (95% CL 0.74 0.94), NNT (odds ratio) at 1 year = 23. CRC (3 studies, 1256 patients), FOLFOX vs non FOLFOX: OR 0.72 (95% CL 0.54 0.98), NNT (odds ratio) at 5 years = 22. mCRPC (2 studies, 1439 patients), DOC vs non DOC: OR 0.78 (95%CL 0.63 0.96), NNT (odds ratio) at 3 years = 16. Conclusions: TAX in BC, DDP in NSCLC and FOLFOX in CRC are the 1st choice cytotoxic approach to metastatic disease, with relative reductions in the risk of death (RRR) of 16%, 17% and 28%, respectively; thus, you will need to treat 28, 23 and 22 patients to prevent one additional death, in the order. DOC had a similar RRR (22%) and the most favourable (16 patients) NNT (odds ratio) in this analysis. Both the quality of evidence and the small number of patients to treat with DOC to avoid one additional death did recommend this chemotherapy in 1st-line mCRPC. [Table: see text]
C-reactive protein as adverse prognostic marker for men with castration-resistant prostate cancer (CRPC): Confirmatory results
Authors: Prins R. , Rademacher B. L. , Mongoue-Tchokote S. , Eilers K. M. , Beer T. M. 
Published: August 2020

5168 Background: We previously reported that higher serum concentrations of C-reactive protein (CRP) are associated with shorter survival in men with metastatic CRPC treated with docetaxel-containing chemotherapy. We sought to confirm these hypothesis-generating findings in an independent data set. Methods: Baseline samples were stored (-80ºC) from 119 CRPC patients enrolled in 6 phase I or II clinical trials of chemotherapy as well as non-cytotoxic agents conducted at OHSU. 91% of patients had metastases and 9% had PSA-only disease. 16% had prior chemotherapy exposure. Median follow-up is 19.7 months (0.9–98.5 months) and 89% have died. In addition to CRP, we examined alkaline phosphatase, hemoglobin, age, ECOG PS, and PSA collected at study entry. After examining the form of the risk function using the generalized additive model method, univariate and multivariate Cox proportional hazard models were used to assess associations between baseline individual categorical and continuous variables. Results: Quartiles of CRP were: 1: 0–1.0, 1.1–4.9, 5.0–17.0, and 17.1 to 311 mg/L, somewhat lower than in our previous study. In a Cox multivariate model, log2(CRP) (HR 1.09 p = 0.036) as well as hemoglobin and log2(Alk Phos) were independently associated with survival. Thus, the risk of death increased 8.7% for every doubling of CRP. Conclusions: In an independent data set from patients with CRPC, we confirmed that higher baseline CRP is associated with shorter survival. This readily measurable biomarker has the potential to improve prognostic models and should be validated in a prospective clinical trial. This finding also suggests that inflammation may play an important role in the natural history of advanced prostate cancer. Additional studies of the mechanisms that may explain the inverse relationship between CRP and survival are under way. No significant financial relationships to disclose.
Early determination of metastatic potential in breast cancer: The 70-gene signature in small tumors
Authors: Knauer M. , Mook S. , Retèl V. , Kok M. , Wesseling J. , Glas A. M. , Rutgers E. J. , van 't Veer L. J. , Linn S. C. 
Published: August 2020

518 Background: Small breast cancers are often considered as low risk tumors in clinico-pathologic risk assessment and treatment guidelines. However, since the ability to metastasize is an early and inherent genetic property of breast cancer and consequently even small tumors can metastasize, identification of prognostic subgroups for patients with small tumors would help to optimize treatment strategies. In the present study the 70-gene prognosis signature (MammaPrint), validated as independent prognostic indicator for node-negative and positive patients, was used to assess prognosis for pT1 breast cancer. Methods: 965 tumor samples of women with pT1 breast cancer from 7 previously reported studies were analyzed and classified by MammaPrint as good or poor prognosis. 10-year distant disease-free survival (DDFS) and breast cancer-specific survival (BCSS) was analyzed according to the 70-gene prognosis signature separately for pT1a/b (1–10mm) and pT1c (11–20mm) tumors. Results: Median follow-up was 7.1 years (range 0.2–25.2). 526 of 965 patients (55%) were classified as good prognosis and 439 (45%) as poor prognosis by the 70-gene signature. 562 patients (59%) received no adjuvant treatment, 19% received hormonal treatment only, 10% chemotherapy only and 12% both respectively. The 70-gene signature accurately predicted differences in 10-year DDFS (HR 2.7 [1.9–3.9], p<0.01) and BCSS (HR 4.0 [2.6–6.3], p<0.01) for all T1 tumors. Similar results were obtained by multivariate analysis for all patients, adjusted for known prognostic factors and adjuvant therapy, as well as for adjuvant untreated patients. At 10 years, for small pT1a/b tumors (n=140), DDFS was 93% vs. 78% for the good and poor prognosis groups (HR 3.9 [1.0–15.2], p=0.048), while in the T1c group (n=825) DDFS was 86% vs. 72% (HR 2.6 [1.8–4.0], p<0.01). BCSS was 87% vs. 73% for the good and poor prognosis groups in the T1a/b group (HR 2.4 [0.8–7.7], p=0.128) and 92% vs. 72% (HR 4.4 [2.7–7.1], p<0.01) in T1c tumors, respectively. Conclusions: The 70-gene signature is a strong and independent prognostic indicator also in small breast tumors. Patients with T1a/b or T1c tumors and a genomic high risk gene signature for developing distant metastases may be selected for additional adjuvant hormonal and chemotherapy. [Table: see text]
Association of the fibroblast growth factor receptor-4 (FGFR4) Gly388Arg polymorphism with clinical and pathological response to primary systemic therapy (PST) for early breast cancer (EBC)
Authors: Marme F. , Sohn C. , Burwinkel B. , Sinn P. , Hahn M. , Lichter P. , Benner A. , Schneeweiss A. 
Published: August 2020

525 Background: The FGFR4 Arg388 genotype has recently been shown to be associated with decreased disease free survival after adjuvant systemic therapy for EBC and thus therapy resistance (Harbeck et al, J Clin Oncol. 2006). Primary systemic therapy (PST) for EBC allows in-vivo chemosensitivity testing. Pathological complete response (pCR) in the breast following PST is associated with improved survival. We evaluated the FGFR4 Gly388Arg polymorphism as a predictive factor for response to PST for EBC in the setting of a prospective, randomized phase 2 trial. Methods: Patients (pts, n = 257) with T2–4/N0–2/M0 EBC were randomized to 4 cycles (cy) A 60 mg/m2 + C 600 mg/m2 day (d) 1 every three weeks (q3w) followed by 4 cy D 100 mg/m2 d1 q3w, or 4 cy A 60 mg/m2 + P 500 mg/m2 on d1 q3w followed by 4 cy D 100 mg/m2 d1 q3w, stratified by hormone receptor (HR) status. Surgery was performed after last chemotherapy. Genotyping was performed using a Taqman Genotyping assay. The genotype was confirmed by RFLP-PCR for 50% of samples with 100% congruence. Results: Genotype was available for 252 of 257 pts enrolled into this study. Using Fisher´s Exact Test there was no correlation between genotype and clinical tumour size (cT), HR status, HER2neu status, grading, menopausal status or triple negative phenotype. The G/G genotype correlates significantly with clinically positive axillary lymph nodes before chemotherapy (p = 0.03). Considering all pts the G/G genotype (vs G/A + A/A) is associated with a significantly lower overall response rate (ORR)(OR 0,47; 65% vs 80%; p = 0.03). Separate analysis of treatment arms showed a significant correlation between the G/G genotype (vs other genotypes) and a lower pCR rate (OR 0.33; 12.5% vs 30.4%; p = 0.04), clinical complete response (p = 0.02) and ORR (OR 0.25; p = 0.01) in the AC-D arm, whereas there was no correlation for pts treated with AP-D. Conclusions: This study provides important evidence that the FGFR4 genotype might serve as a valuable predicitve marker for response to PST with AC-D for EBC. No significant financial relationships to disclose.
What is the optimal strategy to confirm the diagnosis of epithelial ovarian carcinoma (EOC) prior to neoadjuvant chemotherapy (NAC)?
Authors: Dodge J. E. , Mackay H. , Klachook S. , Bernardini M. , Shaw P. , Murphy K. J. , Lo E. , Rosen B. P. , Freedman O. 
Published: August 2020

5511 Background: NAC has been increasingly utilized in clinical practice yet no standard diagnostic strategy has been defined for EOC prior to the administration of NAC. We reviewed the diagnostic process for patients receiving NAC at our centre to determine if an optimal diagnostic strategy could be determined. Methods: A retrospective chart review of all patients known to receive NAC followed by cytoreductive surgery for presumed EOC between 1994 and 2007 was performed. Diagnostic strategies were defined as histology, cytology, and clinical. Performance of these strategies in predicting final pathology, based on expert pathology review of surgery specimens, was compared using Fisher's exact test. Results: 152 patients were included. Initial diagnosis was made on the basis of: cytology (paracentesis/thoracentesis)- 89 (59%); percutaneous biopsy- 40 (26%), radiology and CA-125–18 (12%), surgical biopsy -5 (3%). The final diagnosis was consistent with invasive EOC in 145 patients (95%). The remaining 7 were ovarian LMP (4), ovarian carcinosarcoma (1), endometrial serous cancer (1), and GI tumor (1). The diagnostic accuracies of the 3 strategies differed: histology (43/45), cytology (87/89), and clinical (15/18), p = 0.039. 17% of patients had an alternate final diagnosis when clinical parameters were the only basis for the diagnosis of EOC prior to NAC. A specific EOC subtype was identified pre-op in 82 patients (histology-31 cases, cytology-51 cases). Subtype differed between pre- and post-treatment samples in 13% of histology and 8% of cytology cases. Conclusions: Diagnosis of EOC based on cytology or histology-based strategies are superior to clinical factors alone. Even in a centre with trained gynecologic cytopathologists, cytology and biopsy strategies preclude accurate subtype diagnosis in a significant number of patients. These data are important for clinical practice and the design of future clinical trials. No significant financial relationships to disclose.
Predictors for optimal cytoreduction following neoadjuvant chemotherapy in advanced epithelial ovarian carcinoma
Authors: de Jong D. , Dodge J. E. , Freedman O. , Lo E. , Rosen B. P. , Mackay H. 
Published: August 2020

5512 Background: Neoadjuvant chemotherapy (NAC) is increasingly used to treat patients (pts) with presumed advanced-stage epithelial ovarian cancer (EOC) who are deemed ineligible for upfront debulking surgery (DS). DS following NAC offers a survival benefit to those pts in whom optimal cytoreduction (< 1 cm residual tumor) is achieved. However, not all women who commence NAC have a subsequent attempt at DS. The aims of this study were to identify, in pts planned for NAC, predictive parameters for attempting DS and for achieving optimal cytoreduction in those undergoing surgery. Methods: Pts with presumed stage IIIC or IV EOC who started NAC between 1998 and 2004 were selected for chart review from our institutional ovarian cancer database. Pts with synchronous primary tumors or final pathology inconsistent with EOC were excluded. Age, presence of ascites, Pre NAC hemoglobin (Hb), platelet count (Pls), and CA-125 were explored as possible predictors of attempting DS and of optimal cytoreduction using Kruskal-Wallis analysis and multivariate regression analysis with backward elimination. Results: 212 pts met inclusion criteria. 164 pts (77.4%) had an attempt at DS after NAC; of these 109 pts (66.4%) were optimally cytoreduced. Age and pre-NAC Pls were independent predictors for attempting DS. Median age of pts undergoing DS was 65 years (range 42–82 yrs) compared to 77 yrs (range 54–89 yrs) in those in whom there was no DS attempt, p < 0.01. Median pre NAC Pls of pts undergoing DS was 398 (range 220–685) *109/L, compared to 298 (178–519) for those not proceeding to DS, p < 0.001. Pre NAC Hb, CA125, and ascites were not predictors of DS. Among pts undergoing DS, age was the only independent predictor of optimal cytoreduction identified: median age of pts (optimal vs. suboptimal cytoreduction) was 57yrs (range 42–73 yrs) vs. 67 yrs (49–82yrs), p < 0.001. Presence of ascites, pre-NAC Hb, pre-NAC Pls, and pre-NAC CA-125 were not predictors of optimal cytoreduction. Conclusions: At our centre, pt age and pre-NAC Pls are independent predictors for attempting DS following NAC for advanced stage EOC. In pts undergoing DS age was the only independent predictor of optimal cytoreduction identified. Further investigation of these findings is warranted. No significant financial relationships to disclose.
A phase II evaluation of paclitaxel and carboplatin in the treatment of carcinosarcoma of the uterus: A Gynecologic Oncology Group (GOG) study
Authors: Powell M. A. , Filiaci V. L. , Rose P. G. , Mannel R. S. , Hanjani P. , DeGeest K. , Miller B. E. , Susumu N. , Ueland F. R. 
Published: August 2020

5515 Background: Both platinum and taxane compounds have demonstrated activity in uterine carcinosarcoma (malignant mixed Mullerian tumor). Ifosfamide plus paclitaxel is the regimen supported by randomized phase III trials through the GOG. However, the toxicity, multi-day schedule, and limited activity of this regimen indicate that development of other regimens is still needed. The primary aims of this prospective study were to estimate the antitumor activity and toxicity of paclitaxel plus carboplatin in patients with uterine carcinosarcomas. Methods: Eligible patients had advanced stage (III or IV), persistent, or recurrent measurable disease with histologic confirmation of the primary tumor, no prior chemotherapy, and a GOG Performance Status of 2 or better. At entry hematologic and all other labs were within pre-defined limits. Patients received the combination of paclitaxel 175 mg/m2 IV over 3 hours plus carboplatin (AUC 6) IV over 30 minutes every 3 weeks until disease progression or adverse effects prohibit further therapy. The primary endpoint of confirmed response was assessed by RECIST criteria. CTCAE v3 was used to grade adverse events. This study used an optimal but flexible two-stage design with early stopping guidelines intended to limit patient accrual to inactive treatments. Forty to 47 eligible patients were targeted for accrual. Central pathology review (CPR) is still pending for 5 patients. Results: Fifty-five patients were entered on study with 9 being excluded from analysis; 7 with unconfirmed diagnosis at CPR and 2 were never treated. Treatment was generally tolerated with expected hematologic toxicity and minimal non-hematologic grade 4 toxicity (1 cardiovascular and 2 pain) with 59% of patients completing 6 or more cycles of chemotherapy. The proportion of patients with confirmed complete and partial responses were 11% and 41%, respectively (52%; 95% CI 37%-67%). Additionally 4% experienced an unconfirmed response and 26% had stable disease. Conclusions: Paclitaxel plus carboplatin demonstrates anti-tumor activity against uterine carcinosarcoma with acceptable toxicity and warrants further evaluation in phase III randomized trials. No significant financial relationships to disclose.
Effect of treatment of patients with early-stage uterine carcinosarcoma
Authors: Cantrell L. A. , Havrilesky L. , O'Malley D. , Liotta M. , Secord A. A. , Nagel C. , Fader A. N. , Wallace A. , Rose P. , Gehrig P. A. 
Published: August 2020

5516 Background: The treatment of early stage uterine carcinosarcoma is controversial. We sought to retrospectively review factors that influence progression and survival. Methods: A retrospective, multi-institution study of women diagnosed from 1997–2007 was performed. Postoperative treatment included either observation (OBS), RT (brachytherapy, whole pelvic, or combination), chemotherapy (CT) alone or with RT (CT+RT). Data collected included time to recurrence, overall survival, and sites of recurrence. Statistics included ANOVA and Kaplan Meier. Results: One hundred and forty-six patients were diagnosed with early stage (stages 1 and 2) uterine carcinocarcoma. The median age at diagnosis was 68 years (range:40–91). The majority (62%) were Caucasian, 49 (34%) were African-American and the remainder were other ethnicities. One hundred and seventeen had stage 1 disease and 29 had stage 2. The majority of patients (N = 54, 37 %) were observed, 36 (25%) were treated with CT, 31 (21%) were treated with RT and 17 (12%) were treated with CT + RT. The median progression free survival (PFS) for patients diagnosed with early stage disease was 16.7 months for the OBS cohort and 38.2 months for the CT cohort (p < 0.01). Median overall survival was 23 months for the OBS cohort and 39.3 months for the CT cohort (p = 0.02). The cohorts that underwent RT or CT+RT had improved median progression free (29.9, 20 months) and overall survival (31.7, 20.8 months) as compared to the OBS cohort, however this was not a statistically significant difference. Conclusions: We report on the largest experience in the literature on early stage uterine carcinosarcoma and the first to show that women with early stage disease may benefit from adjuvant chemotherapy. The role of radiation therapy or combination chemotherapy and radiation could not be adequately assessed from this retrospective analysis, but a trend toward improved survival was present. Prospective trials evaluating the best treatment for patients with early stage carcinosarcoma of the uterus should be undertaken to better answer this question. No significant financial relationships to disclose.
Nomogram for predicting 5-year survival after primary surgery for epithelial ovarian cancer
Authors: Chi D. , Zivanovic O. , Kolev V. , Yu C. , Levine D. A. , Sonoda Y. , Abu-Rustum N. R. , Huh J. , Barakat R. R. , Kattan M. W. 
Published: August 2020

5523 Background: Nomograms have been shown to be superior to traditional staging systems for predicting an individual's probability of long-term survival. Our objective was to develop a nomogram based on established prognostic factors to predict the probability of 5-year disease-specific survival (DSS) after primary surgery for patients with epithelial ovarian cancer (EOC) and to compare its predictive accuracy with the currently used FIGO staging system. Methods: We identified all pts with EOC who had their primary staging/cytoreductive surgery at our institution from January 1996-December 2004. DSS was estimated using the Kaplan-Meier method. We analyzed 28 clinical and pathologic factors for prognostic significance. Significant factors on univariate analysis were then included in the Cox proportional hazards regression model, which identified the factors to be used to construct the nomogram. The concordance index (CI) was used as an accuracy measure, with bootstrapping to correct for optimistic bias. Calibration plots were constructed. Results: There were 478 evaluable pts on the study. The median age was 58 years (range 25–96). The primary surgeon in all cases was an attending gynecologic oncologist. All patients received platinum-based systemic chemotherapy postop. DSS at 5 years was 52%. The most predictive nomogram was constructed using the following 7 predictor variables: age, ASA status, family history suggestive of hereditary breast/ovarian cancer syndrome, preoperative serum albumin level, FIGO stage, tumor histology, and residual disease status after primary surgery. This nomogram was internally validated using bootstrapping and shown to have excellent calibration with a bootstrap-corrected CI of 0.721. The CI for FIGO staging alone was significantly less at 0.62 (p = 0.002). Conclusions: We developed a nomogram to predict 5-year DSS after primary surgery for EOC. The nomogram uses 7 variables that are readily accessible, assigns a point value to each variable, and then predicts the probability of 5-year survival based on the total point value for an individual patient. This tool is more accurate than FIGO staging and should be useful for patient counseling, clinical trial eligibility determination, postop management, and follow-up. No significant financial relationships to disclose.
Health-related quality of life/patient-reported outcomes in relapsed ovarian cancer: Results from a randomized phase III study of trabectedin with pegylated liposomal doxorubicin (PLD) versus PLD alone
Authors: Krasner C. N. , Poveda A. , Herzog T. , Vermorken J. , Monk B. , Zintl P. , Li J. , Su Y. , Dhawan R. , Kaye S. 
Published: August 2020

5526 Background: In an open-label, multicenter, randomized phase III study comparing the combination of trabectedin and PLD to PLD alone in patients with relapsed ovarian cancer, the combination demonstrated significantly improved progression free survival and response rates, manageable non-cumulative toxicity, and fewer PLD-associated adverse events. We studied the impact of the combination of trabectedin with PLD on the quality of life (QoL)/patient-reported outcomes (PRO) evaluated as part of the trial. Methods: QoL/PRO questionnaires, EORTC-QLQ C30, OV28, and EQ-5D were completed by patients at screening and on Day 1 of every other treatment cycle starting with Cycle 1, and at the end-of-treatment visit. Global health status/QoL, fatigue, rain subscales from QLQ C30, and abdominal pain/GI symptoms scale from OV28 were chosen a priori for primary analyses. Other scales of the three questionnaires were analyzed on a supportive basis. Results: A total of 672 patients were randomized. 663 (98%) completed at least the baseline questionnaires. Median cycles of treatment was 6 (131 days) for the combination arm and 5 (143 days) for the monotherapy arm. Mixed effects models (using a covariance structure of AR[1]) predicting the score at baseline and follow-up scores as a function of treatment, days after baseline, and interaction between treatment and days after baseline showed no significant differences between the treatment arms for any of the prespecified scales. Similar analyses of other scales, including EQ-5D Health Index scores and Health State on the Visual Analog Scale, support the findings. Conclusions: The addition of trabectedin to PLD results in superior efficacy in patients with relapsed ovarian cancer, with no added decrement to overall health status as assessed by PRO. [Table: see text]