bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is the mesenchymal transition subtype more responsive to dose dense taxane chemotherapy combined with carboplatin (ddTC) than to conventional taxane and carboplatin chemotherapy (TC) in high grade serous ovarian carcinoma? A survey of Japanese Gynecology Oncology Group study (JGOG3016A1).
Authors: Murakami Ryusuke , Matsumura Noriomi , Tanabe Hiroshi , Michimae Hirofumi , Yunokawa Mayu , Iwase Haruko , Sasagawa Motoi , Nakamura Toshiaki , Tokuyama Osamu , Takano Masashi , Sugiyama Toru , Sawasaki Takashi , Isonishi Seiji , Takehara Kazuhiro , Nakai Hidekatsu , Okamoto Aikou , Mandai Masaki , Konishi Ikuo ,   JGOG
Published: September 2018

5510 Background: High-grade serous ovarian cancer (HSOC) was divided into four transcriptome subtypes (i.e. Mesenchymal, Immunoreactive, Proliferative, and Differentiated). We established a new pathological classification based on these transcriptome subtypes: Mesenchymal Transition (MT) type, Immune Reactive (IR) type, Solid and Proliferative (SP) type and Papillo-Glandular (PG) type (PMID: 26993207). The MT type has the worst prognosis. We discovered the Mesenchymal transcriptome subtype might be sensitive to taxane chemotherapy. Therefore, we hypothesized that the MT type, which represents the Mesenchymal transcriptome subtype, may respond better to dose dense taxane combined with carboplatin (ddTC) rather than to conventional taxane and carboplatin (TC). Methods: We collected 207 HSOC slides registered in the Japanese Gynecology Oncology Group 3016 (JGOG3016) study. Two of the authors, R.M. and I.K., classified the samples into the four pathological subtypes (n=201). We categorized the patients into two groups based on the treatment they received: ddTC (n=95) or TC (n=106). Progression free survival (PFS) was compared between the two groups for each pathological subtype. Results: Among the MT patients, the ddTC group had a significantly better PFS than the TC group (n= 30 vs 42, median survival: 1.8 vs 1.2 years, p=0.01). Among the SP patients, the ddTC group had better PFS than the TC group, even though the difference was not statistically significant (n=22 vs 27, median survival: 3.2 vs 1.4 years, p=0.08). In contrast, among the IR patients, the two groups showed no significant difference in PFS (n=16 vs 16, median survival: 5.2 vs 5.8 years, p=0.64). The PG patients also showed no significant difference in PFS between the two groups (n=27 vs 21, median survival: 1.5 and 1.7 years, p=0.64). Conclusions: The HSOC of MT type is more responsive to ddTC than to TC. This new pathological classification reflecting HSOC transcriptome subtypes leads to individualization of chemotherapy treatments.
Functional and oncologic outcomes of radical trachelectomy in early-stage cervical cancer: A prospective multicentric cohort of 61 patients.
Authors: Balaya Vincent , Rossi Lea , Ngo Charlotte , Bats Anne-Sophie , Mathevet Patrice , Lecuru Fabrice ,   SENTICOL Group
Published: September 2018

5529 Background: The aim of this study was to assess the post-operative morbidity of patients who have undergone a radical trachelectomy for early-stage cervical cancer and the oncologic outcomes. Methods: We retrospectively analyzed the data of two prospective trials on sentinel node biopsy for cervical cancer (SENTICOL I & II). Patients underwent a radical trachelectomy for early-stage cervical cancer between January 2005 and March 2012 from 8 French oncologic centers. Results: A total of 61 patients have undergone a radical trachelectomy: 41 patients by laparoscopic-assisted vaginal way, 7 patients by total laparoscopic way, 11 patients by total vaginal way and 2 patients by laparotomy. The median age was 33 years (range = 22-68 years). 88.5 % of patients had a stage IB1 disease. There were 63.9% of epidermoid carcinoma and 34.4 % of adenocarcinoma. Eighteen patients (29.5%) had only a sentinel lymph node biopsy and 43 patients (70.5%) had an additional pelvic lymphadenectomy. The median follow-up was 46 months (range = 0-85 months). Twenty patients (32.8%) had a urinary complication. There were 12 cases of urinary infections (19.6%), 6 cases of dysuria (9.8%), 3 cases of urinary incontinence (4.9%), and one case of ureteral fistula (1.6%). Nine patients had a major neurologic complication (14.7%): the genito-femoral nerve was injured in 4 cases (6.5%) and the obturator nerve was injured in 5 cases (8.2%). Sixteen patients (26.2%) presented a lymphovascular complication. There were 12 cases of limb lymphedema (19.7%) and 5 cases of pelvic lymphocyst (8.2%). During the follow-up, 3 patients (4.9%) had a local recurrence and two patients died : one from a breast cancer and one from a liver metastasis. Conclusions: The radical trachelectomy is a feasible and safe alternative option for young patient with a early-stage cervical cancer in order to preserve their fertility. See table. [Table: see text]
Role of axillary node dissection after mastectomy with positive sentinel nodes.
Authors: Park Tristen Sinae , Thomas Samantha Marie , Greenup Rachel Adams , Hwang Eun-Sil Shelley 
Published: September 2018

554 Background: The ACOSOG Z11 trial demonstrated that sentinel lymph node biopsy (SLNB) alone was safe for women with early stage node positive cancer undergoing breast conservation therapy with radiation. Little data exists regarding management of this population undergoing mastectomy. The purpose of our study is to determine the benefit of axillary lymph node dissection (ALND) or SLNB with adjuvant radiation in patients with 1-3 positive SLN after mastectomy. Methods: Using data from the National Cancer Database (2004-2014), we performed a retrospective review of patients who underwent mastectomy and were clinically node negative at presentation, but were found to have 1-3 positive nodes on pathology. Patients were categorized as undergoing SLNB alone (1-5 nodes examined) or ALND (≥8 nodes examined). Patients who received SLNB without ALND were further categorized by receipt of radiation treatment (RT). Patients with either neoadjuvant chemotherapy or stage IV disease were excluded. Results: Of 42,371 patients, 10.0% had SLNB+RT, 22.4% had SLNB alone, and 67.5% had ALND. Median age of the cohort was 58 years and median tumor size 2.3 cm. Median follow up was 4.1 years. After adjustment for covariates including age at diagnosis, tumor size, chemotherapy, endocrine therapy and receptor status, SLNB+RT had comparable overall survival to ALND (HR = 1.06, p = 0.52), but SLNB alone was found to be associated with a 25% increase in hazard of death compared to ALND (HR = 1.25, 95% CI 1.11-1.41, p < 0.001). Conclusions: In clinically node negative patients with 1-3 positive sentinel nodes treated with mastectomy, SLNB alone was associated with a significantly increased risk of all-cause mortality compared to ALND or SLNB+RT. These results suggests that ALND may be avoided in these patients in the setting of adjuvant radiation, possibly avoiding the morbidity associated with axillary lymphadenectomy.
CD8+ TILs in early stage epithelial ovarian cancer: A GEICO study.
Authors: Romero Ignacio , Leskella Susanna , Redondo Andres , Gutierrez-Pecharroman Ana , Santaballa Ana , Cristobal Lana Eva Maria , Calvo Elisa , Rosa-Rosa Juan Manuel , Oaknin Ana , Bover Isabel , Herrero Ana , Sanchez-Heras Ana Beatriz , Churruca Cristina Maria , De Juan Ana , Mendiola Cesar , Romeo Margarita , Ojeda Belen , Lopez-Guerrero Jose Antonio , Palacios José , Poveda Andres ,   GEICO Group
Published: September 2018

5543 Background: The extent of tumor infiltrating lymphocytes (TILs) has emerged as a potential clinical useful biomarker in epithelial ovarian cancer (OC); however differences in TILs among OC histological types have not been extensively analysed. Methods: From a prospective early stage (I-II) GEICO registry of 1151 cases, 573 were sent for central pathology review. Complete analysis for classification of OC correctly identified 488 cases. Histological typing was performed according to morphological features and the expression of WT1, p53, p16, estrogen receptor (ER), progesterone receptor, and napsin A. The expression of mismatch repair (MMR) proteins MLH1, PMS2, MSH2 and MSH6 was performed in all tumors. The absolute number of stromal and intraepithelial CD8+ TILs per 0.6 mm2 TMA core was quantified and correlated with pathological features. Results: The series included 127 high-grade serous carcinomas (HGSC) (26%), 22 low-grade serous carcinomas (LGSOC) (4.5%), 165 endometrioid carcinomas (EC) (33.8%), 124 clear cell carcinomas (CCC) (2.4%), and 50 mucinous carcinomas (MC) (10.2%). The mean of intraepithelial CD8+ TILs was higher in HGSG (48.7) than in all other histological types (LGSG: 16.3; EC: 27.1; MC: 7.0; and CCC 10.3; p<0.0001). In the stromal component, the mean of CD8+TILs was also higher in HGSG (31.1) than in EC, MC and CCC (15.8, 8.0 and 12.7, respectively; p<0.0001). The mean of intraepithelial CD8+ TILs was significantly higher in RE-positive (71.9) than in RE-negative (34.8) HGSC ( p=0.002). In the complete series, 33 (6.6%) OCs showed absent expression of at least 1 MMR protein, and the mean of intraepithelial CD8+ TILs was significantly higher in these OCs (57.0) than in those with preserved expression of all MMR proteins (23.6; p=0.0035). MMR protein deficiency was observed in 27 (16%) ECs, and these tumours had significantly higher mean of both intraepithelial (60.4 vs. 20.7 p=0.003) and stromal CD8+ TILs (26.6 vs. 13.8, p= 0.046). No significant differences in TILs were observed among EC of different histological grades. Conclusions: The extent of CD8+TILs significantly correlates with the histological type and MMR status in OCs, being HGSCs and EC with MMR deficiency those OCs with higher CD8+TILs.
BRCA-like classification in ovarian cancer: Results from the AGO-TR1-trial.
Authors: Richters Lisa Katharina , Schouten Philip C. , Kommoss Stefan , Hauke Jan , Burges Alexander , Dietrich Dimo , El-Balat Ahmed , Hilpert Felix , Kluin Roel , Heubner Martin Leonhard , Kast Karin , Heimbach André , Braicu Elena Ioana , Schmidt Sandra , Baumann Klaus H. , Jackisch Christian , Linn Sabine C. , Schmutzler Rita K. , Harter Philipp , Hahnen Eric 
Published: September 2018

5546 Background: BRCA associated cancers show a distinct pattern of genomic gains and losses that is associated with impaired repair of DNA double-strand breaks via homologous recombination (HR). We investigated whether BRCA1- and BRCA2-like classifiers could predict BRCA1 and BRCA2 mutation status in ovarian cancer. In addition, we explored whether promoter hypermethylation or mutations in other genes involved in DNA repair associate with a BRCA-like profile in ovarian cancer. Methods: The AGO-TR1 cohort study (NCT02222883 ) enrolled 525 consecutive patients with primary (PR) and platinum sensitive relapsed (RE) ovarian cancer to perform paired mutational analysis of germline and tumor tissue. We performed mutation panel sequencing, BRCA1 promoter hypermethylation and low-coverage whole genome sequencing to classify samples as BRCA1-like or BRCA2-like in 298 ovarian cancer samples (PR: n = 159, RE: n = 139). Results: A BRCA-like profile was observed in 58.1% of the samples without germline or somatic mutation in BRCA1/2 (n = 179; BRCA1-like: n = 26, BRCA2-like: n = 23, BRCA1- and 2-like: n = 55). There was no significant difference between PR- and RE-cases (54.5% vs 61.3%). 64 of 70 BRCA1 germline mutation carriers could be identified by the BRCA1-like classifier (sensitivity: 0.91). The BRCA2-like classifier identified BRCA2 germline mutation carrier with a sensitivity of 0.71 (17 of 24). The complementary use of both classifiers led to the detection of 22 of 25 somatic mutations in BRCA1 (16/16) or - 2 (6/9). Remarkably, 12 of 13 tumor samples from germline RAD51C mutation carriers were recognized by the BRCA1-like classifier (sensitivity: 0.92). No correlation of PALB2 mutation status (n = 7) with BRCA-like profile was observed. Of 28 tumor samples with a BRCA1 promoter hypermethylation 26 had a BRCA1-like profile (sensitivity: 0.93). Conclusions: A high number of ovarian cancer cases display a BRCA-like profile. Mutations (germline and somatic) in BRCA1, BRCA2, RAD51C as well as BRCA1 hypermethylation strongly associate with a BRCA-like profile and can explain 146 of 212 cases. Future studies will investigate whether the classifiers identify patients who benefit from HR-deficiency directed approaches beyond the BRCA mutation status. Clinical trial information: NCT02222883.
Prognostic impact of neo-adjuvant vs adjuvant vs neo-adjuvant plus adjuvant chemotherapy in advanced ovarian cancer: Analysis of National Cancer Database.
Authors: Mukkamala Suresh , Saha Sukamal , Ramanathan Sabarina , Livert David , Oza Rajen , Salib Hayman S. , Bajaj Vinay , Lee Jeen , Wiese David , Arora Madan L. 
Published: September 2018

5552 Background: Patients (Pts) with advanced ovarian cancer (OvCa) are usually treated with primary debulking (deb) surgery (Sx) followed by adjuvant (adj) chemotherapy (CRx). Recently neo-adjuvant (neo-adj) CRx is increasingly being used to reduce the bulk of the tumor. Hence, we analyzed for any prognostic impact of neo-adj vs adj vs neo-adj plus adj CRx along with deb Sx in the management of advanced OvCa. Methods: Only Stage III and IV Pts in National Cancer Data Base (NCDB) from 2006-2014, who underwent deb Sx without bowel resection (1), with bowel resection (2) and with bowel and bladder resection (3) were analyzed. Group (gp) A Pts had neo-adj CRx, gp B had adj CRx and gp C Pts had neo-adj plus adj CRx. The Pearson Chi square testing was used to evaluate the survival between gp A vs B vs C. Results: A total of 20910 Pts in stage III and 7483 Pts in stage 4 were included. Stage III Pts had a better 5 year (yr) survival in gp B compared to gp A and C, in all Pts who underwent Sx 1, 2 and 3 (Table 1). Stage IV Pts had a better 5 yr survival in gp C compared to gp A and B who underwent Sx 1 and 2, and gp B had a better 5 yr survival in Pts who underwent Sx 3 (Table 1). Overall survival was worse for all stages in Pts with neo-adj ( gp A) than gp Band C. Conclusions: Deb Sx followed by adj CRx had better survival than in gp A or C. This may be secondary to less bulkier disease in the beginning in gp B than those in gp A or C requiring neo-adj CRx for the later. Pts survival also improved after addition of adj CRx following deb Sx compared to no adj CRx. A prospective multicenter randomized trial between each group may further validate the true benefits of neo-adj CRx in advanced OvCa. [Table: see text]
Cell-free tumor DNA in peri-operative blood samples from advanced high-grade serous ovarian cancer patients with and without complete resection.
Authors: Heitz Florian , Lakis Sotirios , Harter Philipp , Sehouli Jalid , Talwar Jatin , Sprokmann Mareike , Bertrand Miriam , Ataseven Beyhan , Mariotti Erika , Schneider Stephanie , Müller Judith N , Menon Roopika , Prader Sonia , Leenders Frauke , Hengsbach Alexandra , Gloeckner Christian , Braicu Elena Ioana , Heukamp Lukas C. , Heuckmann Johannes , Du Bois Andreas 
Published: September 2018

5555 Background: Surgical outcome is an important prognostic factor in advanced high-grade serous ovarian cancer (HGOC). Intra-operative determination of residual disease may be prone to subjective bias. Methods: We prospectively collected and analyzed tumor tissue and plasma from 21 pts with FIGO IIIC-IV HGOC. All tumor specimen showed loss of TP53 in immunohistochemistry. Tumor DNA from tissue and peri-operative cell-free DNA at baseline (BL) and at d(ays) 1, d4 and d10 were subjected to comprehensive hybrid-capture based next-generation sequencing (NEO New Oncology GmbH, Cologne, Germany). Results: The initial cohort comprised 10 pts without (TR>0) and 11 pts with complete resection TR0, with a total of 43 somatic genomic alterations. TP53 was mutated in 20/21 (95.2%) of tissue samples and in 15/21 (71.4%) corresponding plasma samples at BL. Therefore, TP53 mutations were used as a molecular marker of circulating tumor DNA levels post-surgery. In the remaining 5 BL cases the TP53 mutations were either not present in plasma (N= 3) or rested below the detection limit (N= 2). In d1, d4 and d10 post-surgical samples, the sample specific TP53 mutations were detected in 12 out of 15, 10 out of 14 and in 7 out of 13 cases, respectively. TP53variant allele frequency (VAF) did not differ among TR0 and TR>0 at BL (mean= 1.91 versus 1.73, Mann-Whitney test p = 0.86) whereas it was significantly lower for TR0 at d1 (mean= 0.06 versus 2,06; p value= 0.002), d4 (mean= 0.07 versus 1.8; p= 0.04) and d10 (mean VAF= 0 versus 1.04; p= 0.008). Five out of 9 TR>0 cases showed at least one increase in VAF between d0 and any additional time-point. In 8 out of 9 mutations remained detectable at d10 (VAF: 0.076 – 3.26). By contrast, TR0 cases showed consistent reduction in VAF throughout the follow-up period which maximized at d10. Conclusions: Liquid biopsycan efficiently detect somatic mutations in the cfDNA of pts with HGOC following debulking surgery. Variation of the TP53 VAF in sequential post-surgical samples appears to be restricted to TR>0 cases, whereas in TR0 pts VAF progressively decreases. Liquid biopsy may hold promise as a tool for the objective determination of residual disease after debulking surgery.
A re-analysis of the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial accounting for ovarian cancer (OVCA) heterogeneity.
Authors: Temkin Sarah Madhu , Miller Eric A , Samimi Goli , Berg Christine D , Pinsky Paul , Minasian Lori M. 
Published: September 2018

5564 Background: A mortality benefit from screening for OVCA has not been demonstrated, but screening efficacy could differ for histologic subtypes. We re-analyzed PLCO evaluating whether OVCA detection and outcomes were affected by the heterogeneous biologic behavior of this disease. Methods: Type 2 tumors (moderately/poorly differentiated serous and adenocarcinoma) were compared to all other tumor (OT) types (low grade serous and endometrioid, clear cell, other, low malignancy potential) (LMP). We examined differences in the distribution of tumor types and stage by study arm and method of diagnosis [screen detected (SD) and interval detected (ID) (i.e. assigned to screening but diagnosed between screening tests)]. Stage distribution and survival were analyzed. Results: Among the entire PLCO population, 531 women were diagnosed with OVCA during the study; 282 (53%) in the screening arm and 249 (47%) in the usual care arm. Of the tumors able to be characterized (n=408; 77%), 74% (n=300) were Type 2 and 26% OT (n=108). In the screening arm, 70% of tumors diagnosed were Type 2 compared to 78% in usual care (p=0.07). Overall, survival was significantly better for OT tumors compared to Type 2 tumors (p<0.01) but there was no difference in survival by study arm for either tumor type separately (Type 2: p=0.50; OT: p=0.23). Within the screening arm, 30% of Type 2 tumors were SD compared to 54% of OT tumors (p=0.02) (see Table). Only 15% of Type 2 SD tumors were Stage I/II, compared to 82% of SD OT tumors (p<0.01). Stage at diagnosis was similar among Type 2 patients whether they were SD or ID (p=0.56) and there was no difference in survival (p=0.56). Conclusions: A significant difference in tumor types by study arm was not observed. However, within the screening arm, Type 2 tumors were less likely to be SD or Stage I/II compared to OT tumors. Survival for Type 2 tumors was similar regardless of method of diagnosis. [Table: see text]
Homologous recombination deficiency and platinum rechallenge in platinum-resistant ovarian cancer patients.
Authors: Da Costa Alexandre Andre B. A. , Salvadori Marcela Marinelli , Valadares Camila Vieira , Stecca Carlos , Brot Louise , do Canto Luisa Matos , Baiocchi Glauco , Rogatto Silvia Regina , Achatz Maria Isabel Waddington 
Published: September 2018

5576 Background: Ovarian carcinomas show homologous recombination deficiency (HRD) in up to 50% of cases and in 15 to 20% of cases occur due to germline BRCA1 or BRCA2 mutations. BRCA mutated tumors are more sensitive to PARP inhibitors and platinum based chemotherapy. The objective of this study was to characterize a cohort of ovarian cancer patients regarding HRD and to evaluate the impact of these scores in prolonged platinum sensitivity. Methods: Thirty one ovarian cancer patients with platinum resistant recurrence reexposed to platinum based chemotherapy were selected. Paraffin embedded tumor samples from 14 patients were analyzed using ONCOSCAN assay (Affymetrix) to evaluate HRD scores. The association of the scores with response rate to platinum rechallenge, overall survival and clinical pathologic factors was evaluated. Results: From the cohort of 31 patients, 15 samples from 14 patients were analyzed for genomic alterations. Median scores were 19.5 for TAI, 12.5 for cnLOH+L, 26.0 for LST and 6.3 for HRD. High scores were found in 10 out of 14 (for cnLOH+L score) and 9 out of 14 (for LST score) patients. Seven of the 14 patients analyzed analyzed for genomic alterations had response, which suggested homologous recombination deficiency. No significant differences were observed between response rates for high versus low scores. Numerically, cnLOH+L, LST and HDR scores were higher in patients with response to treatment compared to those without response. Median overall survival was 13.4 months from the beginning of platinum rechallenge and no difference in survival according to scores was observed. Among the clinical pathologic factors, family history of breast or ovarian cancer or personal history of breast cancer was associated to higher response rate to platinum rechallenge. Conclusions: In conclusion,HRD scores showed to be potential markers of response to platinum rechallenge in the platinum resistant setting. Further studies are necessary to clarify the best cutoffs for each score, the impact of tumor heterogeneity and the analysis of tumor samples in the moment of treatment. Positive family history of cancer is a clinical factor predictvie of platinum rechallenge response.