bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined weekly docetaxel (D) and gemcitabine (G) for relapsed ovarian cancer (OC) and peritoneal cancer (PC): A multi-institutional phase II study
Authors: Morris R. T. , Cohn D. E. , Fowler J. , Solomon L. A. , Vay A. , Seward S. , Heilbrun L. , Smith D. , Munkarah A. R. 
Published: August 2020

5565 Background: Both D and G have demonstrated single-agent activity in OC and PC. The purpose of this study was to prospectively evaluate the efficacy and toxicity for patients (pts) with relapsed platinum-sensitive (Plat-S) and platinum-resistant (Plat-R) OC or PC treated with combination weekly D and G. Methods: Eligibility criteria included women recurrent or refractory to first line platinum based therapy, a performance status of 2 or better, and adequate renal and hepatic function. Only one prior regimen (including maintenance therapy) was allowed. D (40 mg/m2) and G (800 mg/m2) were administered on days 1 and 8 of a 21 day cycle until progression. Best response was defined by RECIST criteria. Granulocyte stimulating factor prophylaxis was not allowed. There were 2 separate 2-stage designs used, one for each stratum: Plat-R and Plat-S, separately for a total planned sample of 62 pts. The primary endpoint was overall response rate (ORR). This study was approved by each center's institutional review board. Results: Thirty pts were enrolled prior to terminating accrual due to lagging enrollment. The median age was 57.5 years (range 41–80). One pt was diagnosed with PC; the remaining 29 had OC. Twenty-seven (90%) pts were response evaluable. The ORR was 59% (90% confidence interval: 0.44 - 0.73). Six pts (22%) achieved a complete response (CR), 10 pts (37%) achieved a partial response (PR) and one pt (4%) had stable disease. Progressive disease was noted in 10 pts (37%). Plat-S pts (n = 16) had a 69% ORR (CR = 31%, PR = 38%) and Plat-R pts (n = 11) had an ORR of 45% (CR = 9%, PR = 36%). Median overall survival was 12.7 months (Plat-S = 14.2 mos. and Plat-R = 6.7 mos.). Toxicity data were evaluable for 29 (97%) pts. Twelve pts (41%) experienced grade 3 or 4 neutropenia; two of these pts also had documented infections. Three pts had grade 3 anemia and 6 (21%) had grade 3 thrombocytopenia. Dose reductions were uncommon (n = 2, 7%). Twelve pts (41%) were hospitalized at least once during treatment. Conclusions: Weekly D and G combination therapy demonstrates significant activity and moderate toxicity in both Plat-S and Plat-R disease. This non-platinum combination deserves further evaluation and may be considered in pts with Plat-S and Plat-R OC and PC. No significant financial relationships to disclose.
A Gynecologic Oncology Group study of associations between polymorphisms in ABC transporter genes (ABCB1, ABCC2, and ABCG2) and outcome in advanced stage epithelial ovarian cancer treated with platinum and taxane chemotherapy
Authors: Darcy K. M. , Tian C. , Ambrosone C. B. , Krivak T. C. , Armstrong D. K. , Bookman M. A. , Davis W. , Zhao H. , Moysich K. , DeLoia J. A. 
Published: August 2020

5567 Background: This study evaluated the relationship between known functional variants in three ATP-binding cassette (ABC) transporter genes (ABCB1 [MDR1], ABCC2 [MRP2], and ABCG2 [BCRP]) and clinical outcomes in epithelial ovarian cancer (EOC). These genes induce resistance to multiple anticancer drugs and some polymorphisms appear to affect expression, stability or activity of these transporters. Methods: Genotypes for common polymorphisms in ABCB1 (G2677T/A, A893S/T -RS2032582 and C3435T, synonymous-RS1045642), ABCC2 (G1249A, V417I-RS2273697), and ABCG2 (C421A, Q141K-RS2231138) were determined in normal blood DNA from 385 women with optimal stage III ECO who participated in a randomized phase III trial (GOG 172 or 182) and were treated with intravenous or intraperitoneal platinum+paclitaxel. Associations between polymorphisms and progression-free survival (PFS) and overall survival (OS) were examined using logrank test and adjusted Cox regression analysis. Results: The genotype distribution for the C421A polymorphism in ABCG2 was 80.7%, 18.5% and 0.8% for CC, CA and AA, respectively. Median time to disease progression or death for the CA+AA versus (vs.) CC genotype in ABCG2 was 30.3 vs. 18.1 months (p = 0.023), or 69.8 vs. 51.6 months (p = 0.172), respectively. After adjusting for clinical covariates, women with the CA+AA vs. CC genotype in ABCG2 had a significant reduction in the risk of disease progression (hazard ratio [HR] = 0.67, 95% confidence interval [CI] = 0.49–0.91, p = 0.01) but not death (HR = 0.77, 95% CI = 0.56–1.08, p = 0.125). The results were consistent across treatments. Adjusted Cox modeling demonstrated that polymorphisms in ABCB1 (G2677T/A or C3435T) and ABCC2 (G1249A) were not associated with PFS or OS. Conclusions: The ABCG2 C421A polymorphism, but not the ABCB1 G2677T/A, ABCB1 C3435T, or ABCC2 G1249A polymorphism, appears to be an independent prognostic factor for disease progression in optimal stage III EOC treated with platinum + paclitaxel therapy. No significant financial relationships to disclose.
Use of Child-Pugh score to assess perioperative outcome in epithelial ovarian cancer patients
Authors: Pua T. , Novetsky A. P. , Blank S. V. 
Published: August 2020

5571 Background: The Child-Pugh score was designed to predict surgical outcome for patients with liver cirrhosis. This score is comprised of five variables (ascites, bilirubin, albumin, prothrombin time and encephalopathy) that were thought to determine prognosis. Epithelial ovarian cancer (EOC) and cirrhosis share manifestations of increased abdominal girth, ascites, malnutrition and abnormal laboratory findings. In this study, we evaluate the application of the Child-Pugh score to assess EOC outcome. Methods: A review of EOC patients (pts) undergoing primary cytoreductive surgery at our institution from 2003 to 2008 was performed. Pts without preoperative serum bilirubin, albumin, prothrombin time or documentation of ascitic volume were excluded. Women were divided into either Child class A (Child score <6) or Child class B/C (>6). Estimated blood loss, ICU admission, minor (infection, transfusion, ileus/bowel obstruction) and major complications (re-operation, peri-operative death, hospital stay >14 days) and survival analysis were evaluated using chi square and Cox proportional hazards model, respectively. Results: A total of 105 patients were evaluated, 29 with early stage (I/II) and 76 with late stage (III/IV) disease. Estimated blood loss was not significantly different between Child class A vs B/C groups (469 ml vs 628 ml, p = 0.45). Optimal cytoreduction was achieved in 92.3% vs 65.8%, respectively (p = 0.001). Post-operative ICU admission (4.8% vs 23.7%, p = 0.004) and minor complication (35% vs 66%, p = 0.003) rates were also significantly lower in the Child A vs B/C group. Of note there were 4 peri-operative deaths, all in the B/C group (p = 0.01). Length of hospital stay between the two groups were 4 vs 8.4 days, respectively (p = 0.008). Women in Child class B/C had a hazard ratio of 12.4 (95% CI 1.5 - 100.7) for death as compared to those in Child class A. Conclusions: Application of the Child classification to women with ovarian cancer revealed increased rates of suboptimal cytoreduction and peri-operative complications including ICU admission, infection, transfusion and death. EOC patients with higher Child score prior to surgery may consider neoadjuvant chemotherapy to decrease morbidity of surgery. No significant financial relationships to disclose.
Prognostic factors of patients with advanced stage serous borderline tumors of the ovary
Authors: Morice P. , Uzan C. , Kane A. , Rey A. , Gouy S. , Pautier P. , Camatte S. , Lhomme C. , Haie-Meder C. , Duvillard P. 
Published: August 2020

5573 Background: The aim of this study was to determine prognostic factors in a large series of patients with stage II or III serous low malignant potential ovarian tumor (LMPOT) and peritoneal implants. Methods: A retrospective review of patients with a serous LMPOT and peritoneal implants treated or referred in our institution. The slides of ovarian tumors and peritoneal implants were reviewed by the same pathologist. Prognostic factors were studied. Results: From 1969 to 2006, 168 patients were reviewed, 21 of whom had invasive implants. Tumors exhibited a micropapillary pattern in 56 patients. Adjuvant treatment had been administered to 61 patients. The median duration of follow-up was 57 (range, 1–437) months. Forty-four patients had relapsed and 10 patients had died. 5-year overall survival of patients was 98%. Among patients with noninvasive and invasive implants, 8% and 10%, respectively, relapsed at 5 years in the form of invasive disease (p = 0.08). Prognostic factors for recurrence in the univariate analysis were: a laparoscopic approach, conservative treatment and positive second-look surgery. In the multivariate analysis the use of conservative treatment was the only prognostic factors for recurrence. Conclusions: The prognosis of serous LMPOT with peritoneal implants remains good. The strongest prognostic factor in patients with an advanced-stage borderline tumor is the use of conservative surgery. In this series, a micropapillary pattern and implant subtypes (invasive vs. noninvasive) were not prognostic factors. No significant financial relationships to disclose.
Clinical relevance of angiogenesis and lymphangiogenesis in patients with sex cord-stromal ovarian tumors
Authors: Brown J. , Deavers M. T. , Nick A. M. , Milojevic L. , Gershenson D. M. , Sood A. K. 
Published: August 2020

5575 Background: Distant metastasis is common in patients with sex cord-stromal ovarian tumors (SCSTs), but lymph node involvement is extremely rare. Given the lack of lymphatics in the normal granulosa layer, we examined the clinical relevance of angiogenesis and lymphangiogenesis in patients with SCSTs. Methods: After Institutional Review Board approval, 80 tumor samples (46 primary, 34 recurrent) were obtained from 65 patients and stained for CD31 (microvessel density; MVD), D2–40 (lymphvascular density; LVD), and VEGF. Clinical data were extracted by chart review and correlated with the angiogenesis and lymphatic markers. Results: The median age of the patients was 42.1 years (range, 8.6–78.6 years). At presentation, 53% of patients had stage I disease, 8% had stage II, 16% had stage III, and 23% were unstaged. Although VEGF expression was noted at some level in 99% of samples, VEGF overexpression (upper tertile of overall score) was noted in 35% of samples. On the basis of ROC analysis, vessel density was stratified into high versus low at a mean MVD cutoff of 12.3. High MVD was present in 41% of all tumors. High MVD was significantly associated with shorter disease-specific survival (mean 16.7 versus 32.3 months; p = 0.024), increased risk of recurrence (p < 0.04), and shorter overall survival (median 108.6 versus 388.5 months; p < 0.001). High MVD was strongly related to VEGF overexpression (p = 0.009). While VEGF expression was not related to the pattern of recurrence, high MVD was strongly associated with distant metastasis (abdomen, liver, lung, bone) compared with local recurrence (p < 0.001). Lymph node metastasis was clinically evident in only 3 of the 65 patients. Most tumors had either absent or low LVD. Interestingly, all 3 tumors with nodal metastasis had significantly greater LVD (LVD = 35.8 vessels/hpf) compared to those without nodal metastasis (LVD = 2.7 vessels/hpf; p < 0.001). Conclusions: Increased angiogenesis is a significant predictor of poor clinical outcome in patients with sex-cord stromal tumors. Most of these tumors have poor lymphatic development that might explain the low likelihood of nodal metastasis. These data provide support for further investigation of antiangiogenic biological agents in these patients. No significant financial relationships to disclose.
Predictive value of gain of 3q for cervical dysplasia and potential utility in the clinical management of LSIL
Authors: Kilpatrick M. W. , Jalali G. R. , Scamporino J. , Menzin A. , Tafas T. , Walat R. , Tsipouras P. 
Published: August 2020

5583 Background: Physicians need better tools for determining whether an LSIL will progress to HSIL or regress. Research demonstrates that the chromosome 3q26 region is found to be amplified in patients with cervical cancer and that the frequency of this 3q gain increases with dysplasia severity. The objective of this study was to demonstrate that 3q can be used as a risk stratification tool to identify patients likely to regress/progress. Methods: Slide-based, archival thin-layer specimens and longitudinal follow-up data for 52 patients (47 usable cases) originally diagnosed as LSIL were obtained from independent cytopathology laboratories. Slides were destained, then hybridized with a single-copy probe for the chromosome 3q26 region and a probe for the centromeric alpha-repeat sequence of chromosome 7, using standard FISH methods. Results: Of the 47 cases analyzed, 30 showed a negative FISH test result for a sensitivity of 92% (95% CI of 64, 100), specificity of 85% (95% CI of 69, 95) and a negative predictive value of 97% (95% CI of 83, 100). In a subset of cases a biopsy was obtained. Of the 32 cases with tissue diagnosis, 11 women had progressed to CIN2+, of which 10 were FISH positive; and 18 of 21 women with tissue diagnosis of ≤CIN1 were FISH negative, for a sensitivity of 91% (95% CI of 59, 100), specificity of 86% (95% CI of 64, 97) and a negative predictive value of 95% (95% CI of 74, 100). If the analysis is confined to the 36 cases for which follow-up of at least 12 months after the index LSIL was available, 26 showed a negative FISH test result for a sensitivity of 100% (95% CI of 48, 100), specificity of 84% (95% CI of 66, 95) and a negative predictive value of 100% (95% CI of 87, 100). Of the 22 cases with tissue diagnosis, 4 women had progressed to CIN2+, all FISH positive; and 16 of 18 women with ≤CIN1 were FISH negative, for a sensitivity of 100% (95% CI of 40, 100), specificity of 89% (95% CI of 65, 99) and a negative predictive value of 100% (95% CI of 79, 100). Conclusions: Analysis of 47 specimens demonstrated the ability of 3q gain to predict disease progression/regression in cytology samples. 3q gain can serve as a risk stratification tool for LSIL cases. [Table: see text]
High interstitial fluid pressure (IFP) and hypoxia as biomarkers of cisplatin chemoradiation response in advanced cervix cancer
Authors: Fyles A. , Pintilie M. , Hedley D. , Bristow R. , Wouters B. , Hill R. , Milosevic M. 
Published: August 2020

5584 Background: Chemoradiotherapy (CRT) has been shown to improve survival compared to RT alone for locally advanced cervix cancer. The tumour microenvironment in cervix cancer is also known to influence disease progression and response to treatment. In this prospective study, pre-treatment tumour hypoxia and interstitial fluid pressure (IFP) were examined as potential biomarkers of improved treatment effectiveness in a cohort of patients treated with definitive radiation alone, or with the addition of concurrent cisplatin CRT. Methods: Between April 1994 and January 2006, 309 eligible patients with cervix cancer were entered into a prospective study of hypoxia and IFP prior to definitive treatment. Patients accrued between 1994 and 1999 (n = 115) were treated with RT alone, and those accrued between 2000 and 2006 (n = 194) received RT and concurrent weekly cisplatin CRT. Clinical characteristics were similar between the two cohorts except pelvic lymph node metastases were more frequent in the CRT cohort (42% vs. 19%, p = 0.0005), likely due to changes in definition of positive nodes on CT or MR imaging. The median follow-up was 3.6 years (2.9 years for CRT and 7.8 years for RT). Results: The use of CRT improved outcome in hypoxic tumors compared to RT (57% 3-yr DFS vs. 42%, p = 0.045) with a trend to improved DFS in patients with high IFP tumors (57% 3-yr DFS vs. 44% for RT alone, p = 0.056). A strong interaction was identified between IFP and treatment (CRT vs. RT, p = 0.007). After correcting for the effects of clinical prognostic factors, cisplatin significantly improved DFS in the high IFP group (p = 0.02), and showed a trend towards improved DFS in those with hypoxia (p = 0.1). In patients with both high IFP and hypoxia a similar benefit of cisplatin was seen. Conclusions: Patients with high IFP and hypoxic tumours may selectively benefit from the addition of concurrent cisplatin CRT to their treatment regimen. This observation is contrary to an effect of high IFP on impaired drug delivery, but may reflect reduced DNA repair under hypoxic conditions, which could facilitate cell killing with both radiation and cisplatin chemotherapy. No significant financial relationships to disclose.
Secondary platinum therapy in patients with uterine cervical cancer previously treated with platinum chemotherapy
Authors: Tanioka M. , Katsumata N. , Hirata T. , Yunokawa M. , Yonemori K. , Kouno T. , Shimizu C. , Tamura K. , Andoh M. , Fujiwara Y. 
Published: August 2020

5588 Background: Second-line chemotherapy after the front-line platinum based regimens including concurrent chemoradiation (CCRT) has not been established for patients with advanced or recurrent cervical cancer. Platinum based regimens are often selected, but the predictive and prognostic factors of secondary platinum therapy are unclear. We therefore evaluated the relative influence of platinum free interval ( PFI ) between the completion of front-line regimen and the institution of second-line regimen. Methods: This retrospective review was undertaken of 65 patients who received ≥ 2 platinum-based regimens and were assessable for secondary response in National Cancer Center Hospital between 1996 and 2008. We analyzed independent predictive factors associated with secondary response by logistic regression model and prognostic factors associated with subsequent survival by Cox regression model. Results: The median age was 54 years old (range, 28 to 73). The median follow-up of subsequent survival was 11.0 months (1.1 to 66.6). The median PFI was 11.1 months (0.7 to 77.6). Overall secondary response rate was 40%, while response rate for 36 patients after CCRT was 36%. The response increases in frequency with longer PFI ( Table ). Univariate and multivariate analyses using logistic regression model showed PFI for ≥ 9 months (odds ratio [OR] = 0.28; P =.04), PS 0 (OR = 0.19; P =.006) and maximum tumor diameter ≥ 30 mm (OR = 0.23; P =.02) were independent predictive factors of secondary response. Univariate and multivariate analyses using Cox regression model revealed PFI for ≥ 9 months (hazard ratio [HR] = 0.44; P =.005), PS 0 (HR = 0.30; P =.000) and histology of squamous cell carcinoma (HR = 2.20; P =.02) were independent prognostic factors of subsequent survival. Conclusions: Our exploratory study demonstrates that platinum free interval has both predictive and prognostic value for secondary platinum-based treatment for patients with advanced or recurrent cervical cancer. [Table: see text] [Table: see text]
Incidence of adnexal and lymph node metastases in endometrial stromal sarcoma
Authors: dos Santos L. , Garg K. , Diaz J. P. , Soslow R. A. , Hensley M. L. , Alektiar K. M. , Barakat R. R. , Leitao M. M. 
Published: August 2020

5589 Background: To determine the incidence of adnexal and lymph node (LN) metastases in endometrial stromal sarcoma (ESS). Methods: We identified all cases evaluated at our institution with a diagnosis of ESS from January 1, 1980 to December 31, 2007. All uterine pathology was reviewed at our center. High-grade or undifferentiated tumors and ESS arising in extrauterine sites were excluded. Pertinent clinical data were abstracted from electronic medical records. Appropriate statistical tests were performed using SPSS 15.0. Results: We identified 91 cases with ESS. All except two underwent hysterectomy. Eighty-four cases (92%) underwent salpingo-oophorectomy (bilateral in 81 [96%]). Adnexal metastases were identified in 8 (9.5%) of 84 cases. All adnexal metastases were manifested by gross adnexal tumor and occurred in patients with other gross pelvic extrauterine disease. Seven of these 8 patients also had lymph-vascular space invasion (LVSI). LVSI status was not reported in the other patient. In patients with gross pelvic extrauterine disease, adnexal metastasis did not affect survival. LN metastases were identified in 8 (24%) of the 34 patients who underwent LN evaluation. Thirty-three evaluations were performed intraoperatively and one was via postoperative CT-guided biopsy of an enlarged LN. Five of the 8 cases with LN metastases had LVSI. LVSI status was not reported in the other 3 cases. Of 20 patients with disease grossly limited to the uterus and grossly normal LN, 2 (10%) had LN metastases. Both of these cases had LVSI and extensive myoinvasion approaching the serosa. Four of the remaining 6 patients with LN metastases had grossly positive LN and other gross extrauterine disease. The final 2 patients had grossly positive LN without other extrauterine disease. Conclusions: The incidence of LN metastases in ESS is most commonly associated with gross extrauterine disease, extensive myoinvasion and LVSI. However, since myoinvasion and LVSI status often are not assessable at the time of initial hysterectomy, LN dissection remains a reasonable option at primary surgery. The rate of adnexal metastasis appears to be negligible in the absence of gross adnexal and extrauterine tumor, but there may be a role for oophorectomy in the hormonal management of ESS. No significant financial relationships to disclose.
Evaluation of the role of aromatase inhibitors (AIs) in the treatment of uterine leiomyosarcoma (uLMS)
Authors: O'Cearbhaill R. , Zhou Q. , Iasonos A. , Soslow R. A. , Leitao M. M. , Aghajanian C. A. , Hensley M. L. 
Published: August 2020

5590 Background: Although AIs are sometimes used in selected patients with uLMS, there are few data assessing the efficacy of AIs in this setting. Methods: A retrospective electronic medical record review of patients (pts) with uLMS treated with an AI at Memorial Sloan-Kettering Cancer Center between 1998–2008 was performed. The primary endpoint was progression free survival (PFS), defined as time from the start of AI until death, progression or last follow-up. PFS was estimated by Kaplan-Meier method. Best response using RECIST was also assessed. Results: 34 pts with advanced, measurable uLMS were treated with AIs. Median age was 53 yrs (range 35–74); median body mass index 28.1 kg/m2 (range 16.1–52.1); LMS grade low: 5, high: 29; hormone receptor status: 19 ER+, 9 ER-, 6 ER unknown, 9 PR+, 9 PR-, 16 PR unknown; low volume of disease (no lesion >2 cm): 19 pts(56%), high volume: 15 pts (44%). 23 pts (68%) had had prior chemotherapy (1 regimen: 29%, 2 regimens: 18%, 3 regimens: 15%, >4 regimens: 6%); 12 pts (35%) had had prior pelvic radiotherapy. AIs used were: letrozole 74% (9% with leuprolide if premenopausal), anastrozole 21%, exemestane 6%. Median PFS was 2.9 months (95% CI: 1.8–5.1). 8 pts (23.5%) had a PFS >6months. Among pts with ER or PR + uLMS, median PFS was 5months (95% CI: 1.8–9.4) versus 1.9months (95% CI: 0.9–3.2) with ER and PR negative uLMS. Best response was partial response in 3 pts (8.8%) (all of whom were ER+), stable disease in 12 (35%), and progressive disease in 19 (56%). Common toxicities were grade 1–2 asthenia (30%), hot flashes (30%), and arthralgias (27%). Conclusions: In this highly selected population of pts with uLMS AIs fail to achieve objective response. While relatively prolonged PFS was observed among ER and/or PR+ uLMS pts, in the absence of a no-treatment control group this outcome cannot be attributed solely to the activity of the AI treatment. No significant financial relationships to disclose.