bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Gynecologic Oncology Group study of frequent copy number aberrations in African American versus Caucasian women with stage I versus stage IIIC/IV endometrioid endometrial cancer
Authors: Morrison C. , Gaile D. , Darcy K. , Liu S. , Shepherd L. , Cohn D. , McMeekin S. , Nowak N. , Maxwell L. 
Published: August 2020

e16501 Background: An array-based comparative genomic hybridization (aCGH) analysis was performed to determine if frequent (>40%) copy number aberrations (CNAs) exist in African American (AA) versus Caucasian (C) women with stage I versus stage IIIC/IV endometrioid endometrial cancers (EEC). Methods: Tumor DNA was isolated from 80 frozen primary tumors from the GOG-210 protocol. RPCI 19K BAC arrays were hybridized (GeneTAC HybStation) and scanned (Gene Pix 4200AL Laser Scanner). Spot fluorescence values were quantified using ImaGene, vetted for quality and loess corrected with adjustments for chip-specific spatial effects. The genome was segmented to identify regions with common copy number means (DNAcopy software). Posterior aberration probabilities for the regions were obtained using CGHcall and data was visualized and annotated using iGenomicViewer in R. Validation will be performed by fluorescence in situ hybridization using select BAC probes and endometrial cancer tissue microarrays (TMAs) with either 400 cases linked with clinical, treatment and outcome data or 180 AA versus 120 C women from GOG-136. Results: Recurrent CNAs were identified in all stage and race groups. Distinct genomic losses and gains were observed that appear to segregate Caucasian women with stage I disease from African American women with stage I disease and African American or Caucasian women with stage IIIC/IV disease. Conclusions: The GOG-210 bank yielded high quality DNA for detecting and mapping CNAs in frozen primary tumors with high resolution. Our results would imply that racial disparity for AA EEC has a genetic basis regardless of stage. Validation studies are currently underway in two endometrial cancer TMAs. [Table: see text] No significant financial relationships to disclose.
Can primary recurrences in surgical stage I-II uterine papillary serous carcinoma (UPSC) patients be salvaged?
Authors: Fader A. Nickles , Rose P. G. , Frasure H. , Gehrig P. A. , Moore K. N. , Havrilesky L. J. , Huh W. K. , Axtell A. E. , O'Malley D. M. , Zanotti K. M. 
Published: August 2020

e16503 Background: There is an absence of data in the literature on salvage rates for vaginal, pelvic, and extra-pelvic recurrences for early-stage UPSC patients (pts). The purpose of this study is to determine whether primary recurrences can be salvaged with chemotherapy or radiotherapy. Methods: A retrospective, multi-institution study of pts with stage I-II UPSC diagnosed from 1993–2006. All pts underwent comprehensive surgical staging. Postoperative treatment included either observation (OBS), radiotherapy (RT: brachytherapy, pelvic, abdominal or combo) or ≥ 3 cycles carboplatin/paclitaxel (CT) alone or with RT (CT+RT). Results: We identified 197 stage I-II pts; 44/197 (22.3%) experienced a primary recurrence during a median follow-up of 35 months. Patterns of recurrence analysis revealed that 17 (38.6%) were vaginal/pelvic (V/P) and 27 (61.4%) were extra-pelvic (EP). Multi-site relapses occurred in 13/44 (30%). Pts initially treated with adjuvant CT±RT (n = 108) had a significantly decreased risk of primary recurrence (9.9%) when compared to those patients treated with RT alone (n = 45; 37%) or OBS (n = 43; 35%; p < 0.001). There were no distinguishing risk factors for development of V/P versus EP recurrence. Median time to recurrence after diagnosis was 16 months. The majority of pts (86%) were not salvaged by second line therapy, with a median time from recurrence to death of 8.9 months. However, more pts with isolated vaginal recurrences (5/12 or 42%) were salvaged when compared to those with pelvic or EP recurrences (1/32 or 3.1%; p = 0.004). The 5 pts who are NED after vaginal relapse were treated with CT±RT (n = 3) or RT (n = 2); 80% had not received prior treatment and 20% had received prior CT. To date, more pts with EP recurrence are dead of disease (23/27) than with V/P recurrences (7/17; p = 0.003). Conclusions: Stage I-II USPC pts are more likely to experience an extra-pelvic than vaginal/pelvic primary recurrence, are unlikely to be salvaged and will have a short interval from recurrence to death. The exception is in those with isolated vaginal recurrence, who may be salvaged in select cases. The current best strategy to avoid primary recurrences in this setting is an initial staging surgery followed by adjuvant carboplatin/paclitaxel. No significant financial relationships to disclose.
Tailored surgical staging and radiation therapy in clinical stage I endometrioid endometrial adenocarcinoma (EEA)
Authors: Bermudez Wagner K. M. , Thomas M. B. , Miyamoto C. , Micaily B. , Hernandez E. 
Published: August 2020

e16511 Background: Pelvic lymph node dissection (LND) requirement to adequately stage endometrial cancer has been subject of debate. We conducted an outcome analysis of clinical stage I endometrioid endometrial adenocarcinoma (EEA) patients who underwent surgery with tailored LND and adjuvant therapy (radiation (RT) or chemotherapy) between 1997 and 2008. Methods: Retrospective chart review was performed at our institution. All patients underwent exploratory laparotomy, cytology, total abdominal hysterectomy and bilateral salpingoophorectomy. Pelvic and para-aortic LND was perforned in high-risk patients when technically possible. Cox proportional hazards and the Kaplan Meier method were used for data analysis. Results: 119 patients (stage I 92, II 11, III 15, and IV 1) were identified. Median BMI was 34 and 81% had significant co-morbidities. 50% underwent para-aortic LND (median 4 nodes) and 25% underwent pelvic LND (median 15 nodes), of whom 8% and 10% were positive, respectively. Postoperative complications occurred in 22%. 26% received RT. With a mean follow-up of 20 months, 5-year progression-free survival (PFS) and overall survival (OS) was 71% and 84%. The OS for stage I and IIIC was 88% and 83%, respectively. OS for patients with or without LND was not statistically different ( 73% vs.82%). 12 (10%) recurrences were noted, 8 of which were hematological (HF) with a 5-year HF probability of 21%. On multivariate analysis only myometrial invasion > 50% was independent risk factor for HF. Patients receiving RT showed a trend toward decreased in local recurrences ( 0% vs.30% p = 0.1) but no improvement in OS. Conclusions: In patients with EEA, a tailored approach to LND and adjuvant therapy results in good outcome, but many still have therapy-associated adverse events. Although no difference was found in OS between patients who underwent LND and those who did not, similar survival for patients with stages I and IIIC suggests that therapy directed by the knowledge of nodal status may have an impact on survival. No significant financial relationships to disclose.
The prognostic significance of supradiaphragmatic lymphadenopathy identified on preoperative computed tomography scan in patients undergoing primary cytoreduction for advanced stage epithelial ovarian cancer
Authors: Kolev V. , Mironov S. , Mironov O. , Moskowitz C. , Ishill N. M. , Gardner G. J. , Levine D. A. , Hricak H. , Barakat R. R. , Chi D. S. 
Published: August 2020

e16512 Background: It has been hypothesized and shown in animal studies that the supradiaphragmatic lymph nodes serve as the principal nodes for lymphatic drainage of the entire peritoneal cavity. The purpose of this study was to determine the prognostic significance of enlarged supra-diaphragmatic nodes noted on preoperative computed tomography (CT) scan in patients with advanced epithelial ovarian cancer (EOC). Methods: We performed a retrospective chart review of all patients (pts) with FIGO stage III and IV EOC who had preoperative CT scans of the supradiaphragmatic region and primary cytoreductive surgery at our institution between 1997 and 2004. All scans were retrospectively reviewed by one board-certified radiologist (SM). To evaluate survival, Kaplan-Meier methods were used, with log rank Pvalues for comparisons. Results: A total of 212 eligible pts who underwent attempted primary cytoreduction followed by platinum-based systemic chemotherapy were identified for evaluation. With a median follow-up time of 52 mos, there were 135 deaths and a median overall survival of 48 mos (95% CI: 44–53). Of the 212 pts, 44 (21%) had supradiaphragmatic adenopathy with nodes >1 cm, while 168 (79%) did not have adenopathy in this distribution. None of the 44 pts with adenopathy had the enlarged nodes removed at primary cytoreduction. The median survival was 49 mos for pts with and 48 mos for patients without adenopathy (p = 0.46). In total, 155 (73%) patients underwent optimal cytoreduction (residual disease ≤ 1 cm). In the optimally cytoreduced pts, the median survival for the 125 pts without supradiaphragmatic adenopathy was 52 mos (95%CI: 45–59) compared to 51mos (95%CI: 41–58) for the 30 pts with supradiaphragmatic adenopathy (p = 0.33). Conclusions: Although a previous study has shown that supradiaphragmatic adenopathy was associated with poorer overall survival in EOC patients, our study did not confirm these findings. In our study, enlarged supradiaphragmatic nodes noted on preoperative CT scan did not have significant prognostic impact and therefore their clinical significance remains uncertain. No significant financial relationships to disclose.
Molecular characterization of highly tumorigenic cell lines used in a xenograph model to investigate cellular therapy for the treatment of refractory ovarian cancer
Authors: Ingersoll S. B. , Yue P. , Ahmad S. , Turkson J. , Edwards J. R. , Holloway R. W. 
Published: August 2020

e16516 Background: Because current therapies for ovarian cancer (OC) have little impact on the long-term survival, there is a compelling need to develop innovative strategies. Our aim was to characterize OC cell lines which can be utilized to test cellular therapy in combination with cytokines or chemotherapies to elicit a graph versus tumor response to treat refractory OC patients. Methods: SKOV-3-RFP, a red fluorescent protein (RFP) expressing line, was passaged through nude mice to create more tumorigenic lines compared to parental SKOV-3 cells. Three SKOV-3-derived lines were established and characterized for IFNα-2b sensitivity, E-cadherinand CCN1gene expression, and STAT3 activation. The cells were grown in the presence of IFNα-2b to determine proliferative effects. Tumors were harvested when mice became moribund; ascitic fluid (AF) and solid tumor (ST) tissue were snap-frozen. Expression of E-cadherinand CCN1, which have been implicated to play role(s) in OC pathobiology, were analyzed in ST harvested from the mice and from SKOV3-derived lines (SKOV3-RFP, AF1, AF2, and AF3). We investigated the activation status in the SKOV3-derived cells of STAT3, which has been associated with malignant transformation and tumor progression. Results: Parental SKOV3-RFP cells when injected at a dose of 5x106 gave a tumor incidence of 4/6 in 14 weeks. AF1 and AF2, when injected at a dose of 1x106 resulted in 100% tumor incidence in 5-weeks (n = 5). These two lines were also more resistant to IFNα-2b compared to RFP. All SKOV3-derived lines and ST expressed E-cadherin by RT-PCR. None of the SKOV3-derived lines expressed CCN1; however, one of the two AF1 ST tested expressed CCN1. Both AF2 ST evaluated showed weak expression of CCN1. In vitro DNA-binding with electrophoretic mobility shift assay (EMSA), showed AF1 and AF3 cells harbor constitutively-active STAT3, whereas the RFP line does not. Conclusions: The SKOV3-derived lines that we developed will be a better model to test novel OC treatment regiments because these lines exhibit increased resistance to IFNα-2b, are more tumorigenic in a xenograph model, show aberrant STAT3 activation, and tumors harvested from these lines express genes that make these lines more aggressive. No significant financial relationships to disclose.
Neoadjuvant transarterial chemoembolization (TACE) using cisplatin with the combination of dose-dense intravenous administration of paclitaxel for the locally advanced cervical adenocarcinoma
Authors: Tsubamoto H. , Wada R. , Kanazawa R. , Komori S. , Maeda H. , Hirota S. , Adachi S. 
Published: August 2020

e16518 Background: Adenocarcinoma (including adenosquamous carcinoma) of the uterine cervix has a tendency to early lymph node metastasis and is resistant to radiation therapy, thus results in poor prognosis compared with squamous cell carcinoma. Neoadjuvant chemotherapy (NAC) followed by radical hysterectomy (RH) for bulky cervical adenocarcinoma seems to be an alternative therapy to primary radiation. Methods: P2 at the single institution. Eligible criteria were as follows: Histologically diagnosed cervical adeno or adenosquamous carcinoma with FIGO stage IB2-IVA, Age < or equal to 75, PS 0–2, given informed consent. The NAC regimen consisted of paclitaxel (60mg/m2, iv, D1, D8, D15) and cisplatin (70 mg/m2, trans-uterine arterial infusion followed by embolization using the gelform, D2) repeated every 3 weeks for 2–3 cycles, followed by RH. Primary endpoints were clinical and pathological responses, and secondary endpoints were toxicities, relapse free survival (RFS) and overall survival (OS). Results: Enrolled patients: 22 (1998–2006), Age: median 51 (33–75), FIGO stage: IB2 (9), IIA-IIB (8), IIIB (3), IVA (2), adeno/adenosquamous: 16/6. Toxicities during NAC (CTCAE ver.3) were as follows: G3/G4 neutropenia 18% (4/22), G3/G4 anemia 14% (3/22), G3/G4 thrombocytopenia 0%, G2/G3 sensory neuropathy 0 %, G3/G4 creatinine elevation 0%, G2 alopecia 100%. Clinical response rate (RR: CR+PR) of the patients with stage IB2-IIB was 100%. 16 of 17 received RH, and no residual malignant cells were found pathologically (pCR) in 3. RR of the patients with stage IIIb-IVa was 80%, three patients completed RH with either modified anterior or posterior exenteration, and pCR was found in one patient. The rate of radiation therapy following either NAC or surgery among enrolled patients were 18% (3/17) with stage IB2-IIB and 40% (2/5) with IIIB-IVA. 5 year RFS/OS were 69%/68% with stage IB2-IIb and 60%/60% with stage IIIb-IVa. All 15 alive patients had RH. One patient with stage IVa had urostomy, and other 14 patients have no trouble in urination function. Conclusions: TACE with cisplatin and dose dense paclitaxel in the neoadjuvant setting is feasible and effective for cervical adenocarcinoma. [Table: see text]
The relevance of rising CA-125 levels within the normal range in predicting recurrence in patients with advanced stage ovarian cancer: A validation study
Authors: AbuShain F. , Escobar P. , Shahabi S. , Michener C. , Drake R. , Rose P. G. , Schwartz P. E. 
Published: August 2020

e16521 Background: Small published series suggested that three progressively rising CA-125 values, doubling of CA-125, and an absolute rise of 5 U/mL from the nadir, all while remaining in the normal range were highly associated with disease recurrence. This study aims to validate these proposed criteria in a larger population. Methods: We conducted a retrospective review of the records of patients with stages IIIC and IV epithelial ovarian cancer treated with primary surgery and adjuvant chemotherapy between 1994 and 2006. Only patients who had a complete response to chemotherapy verified by normal CT scan, CA-125 and physical examination were included. Nadir CA-125 level was defined as the first CA-125 measurement after completing chemotherapy. Available CA-125 values from diagnosis to recurrence or to last follow up were collected and evaluated for meeting any of the criteria above. Results: 91 patients with a median age of 59 (42 - 88) met the inclusion criteria. 82 patients had stage IIIC (90%) and 9 patients (10%) had stage IV. 86 patients (94.5%) had papillary serous histology and 88 patients had grade 3 (96.7%) disease. Median follow up was 43.7 months (12.6 - 156). Table 1 shows the number of patients who met any of the above CA-125 criteria in total and divided by the presence or absence of recurrence. There was no statistically significant difference in meeting any of the CA-125 criteria between the recurrence and no recurrence groups. Meeting at least one of the CA-125 criteria had 50% sensitivity, 65% specificity, and 86% positive predictive value for recurrence. The median time to recurrence in patients who met at least one CA-125 criteria was 3.8 months (0.2 - 12.4) and the median follow up time after meeting one of the CA 125 criteria in patients who did not recur was 88.5 months (10.4 - 188) Conclusions: Rising CA-125 levels within the normal range that meet any of the above criteria are highly predictive (86%) of recurrence within 12 months and closer observation is warranted. [Table: see text] No significant financial relationships to disclose.
Dysgerminoma of the ovary 35 years on: A single institutional experience
Authors: Vicus D. , Beiner M. , Klachook S. , Le L. , Ginsburg O. , Laframboise S. , Mackay H. 
Published: August 2020

e16523 Background: Ovarian dysgerminomas are rare but are relatively more common in women under 20 years of age in whom fertility is likely to be an issue. The aim of this study was to review our institutional experience in treating patients (pts) diagnosed with pure dysgerminoma. Methods: We performed a retrospective chart review of all pts diagnosed with ovarian dysgerminoma at the Princess Margaret Hospital, Toronto, between 1970 and 2005. Results: 65 pts were diagnosed with ovarian dysgerminoma, median age 21.9 years (range 8.1–64.1 yrs). 40 pts (62.5%) presented with FIGO stage IA disease; 3 (4.7%) stage IB; 6 (9.4%) stage IC; 2 (3.1%) stage II; and 13 (20.3%) at stage III, 1 unknown. Initial management was surgical for all pts: unilateral oopherectomy 47 pts (72.2%), 14 (21.5%) bilateral oophorectomy ± hysterectomy (12 pts), 3 (4.6%) cystectomy alone. 17 pts received chemotherapy, 15 adjuvant and 2 for residual disease (all post 1988); 8 for stage I, 1 for stage II, and 8 for stage III. 12 pts received etoposide and cisplatin (EP); 4 bleomycin, etoposide, and cisplatin (BEP); and 1 vincristine and cisplatin. 20 pts received adjuvant radiotherapy (all prior to 1985); 14 stage I; 1 stage II; and 5 stage III. 1 pt received a combination of adjuvant chemotherapy and radiation. 6 (9.2%) pts recurred all within 19 months of initial diagnosis. 5 of the 6 pts that recurred had stage IA disease treated with a unilateral oophorectomy, 1 received adjuvant EP. 1 pt with stage IIIC disease recurred following bilateral oophorectomy + hysterectomy and radiotherapy. Treatment of recurrent disease was by salvage surgery and chemotherapy (3 pts), radiotherapy (2 pts), and EP (1 pt). All pts who recurred responded to treatment and were alive at last follow up, median follow up 22.5 yrs (range 9.3–31.4 yrs). Median follow up, all pts, was 10.5 yrs (range 1.1 to 31.9 yrs). 15 pts attempted to conceive posttreatment; 6 had received adjuvant treatment; 4 EP; and 2 whole abdominal radiotherapy. 13 successful pregnancies and 13 live births were reported in 9 women (3 had received adjuvant EP). Conclusions: The long-term outcome of patients with an ovarian dysgerminoma is excellent. Recurrences occured within 2 years of diagnosis and are treatable. Patients can be treated with fertility sparing surgery and can expect good reproductive outcomes. No significant financial relationships to disclose.
Chemoradiation in locally advanced cervical carcinoma: An analysis of cisplatin administration and other clinical prognostic factors
Authors: Nugent E. , Case A. S. , Zighelboim I. , DeWitt L. , Thaker P. H. , Massad L. S. , Powell M. A. , Mutch D. G. , Trinkhaus K. , Rader J. S. 
Published: August 2020

e16525 Background: The standard treatment for locally advanced cervical cancer is combination weekly cisplatin and radiotherapy (RT). Toxicity and compliance issues often result in failure to complete the recommended six cycles of weekly chemotherapy. Our objective was to retrospectively evaluate the effect of number of chemotherapy cycles and other clinical and pathologic factors on progression-free (PFS) and overall survival (OS). Methods: Between January 2004 and May 2007 we identified 118 patients at our institution with locally advanced cervical cancer (stage 1B2-IVA) treated with combined weekly cisplatin (40 mg/m2) and RT from chemotherapy log records. PFS and OS were evaluated for associations with number of chemotherapy cycles as well as other clinical and pathologic factors. Kaplan-Meier and Cox proportional hazard models were utilized for statistical analyses. Results: The median age and BMI were 51 years (25–86) and 29.2 kg/m2 (15–69). The majority of patients had stage IB2 or II disease (70%), squamous histology (91%), and size <6 cm (65%). Median RT duration was 50 days and 95% received brachytherapy. 30% of patients completed fewer than 6 cycles of chemotherapy and estimated PFS and OS were 63% and 75% respectively. 32 recurrences were detected with a median time to progression of 27 months. In multivariate analyses, number of chemotherapy cycles was independently predictive of PFS and OS. Patients that received <6 cycles of cisplatin had a worse PFS (HR 2.65; 95%CI 1.35–5.17; p = 0.0045) and OS (HR 4.47; 95% CI 1.83–10.9; p = 0.001). Additionally, advanced stage, longer time to RT completion, and absence of brachytherapy were associated with decreased OS and PFS (p < 0.05). Higher grade was associated with decreased PFS (p = 0.03) but not OS. Age, race, BMI, tumor size, smoking, histology, and IMRT were not statistically significant for OS or PFS. Conclusions: Number of cisplatin cycles, stage, grade, time to radiotherapy completion, and brachytherapy, are prognostic of PFS and OS in patients with cervical cancer undergoing treatment with combined cisplatin and RT. Efforts to decrease toxicity and improve compliance allowing for completion of six cycles of cisplatin may be associated with increased progression free and overall survival. No significant financial relationships to disclose.