bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in the receipt of guideline care and survival for women with ovarian cancer.
Authors: Warren Joan , Harlan Linda C , Trimble Edward Lloyd , Stevens Jennifer , Grimes Melvin , Cronin Kathleen A 
Published: September 2018

5540 Background: Guideline care has been found to improve survival for women with ovarian cancer, yet many women do not receive appropriate care. We assessed trends in the receipt of guideline care and 2-year cause-specific survival for women diagnosed with ovarian cancer. Methods: This retrospective cohort analysis used National Cancer Institute’s Patterns of Care studies data for women diagnosed with primary ovarian cancer in 2002 and 2011 (weighted n=6867). Data included patient characteristics, type of treatment, and provider characteristics. We used logistic regression to evaluate the association of year of diagnosis with receipt of guideline surgery, multiagent chemotherapy, or both. Two-year cause-specific survival, 2002-2013, was assessed using SEER data. Results: Forty-six percent of women received stage-appropriate surgery, unchanged from 2002 to 2011. The percent of women seeing a gynecologic oncologist (GO) 2002 to 2011 increased from 43% to 77%, 53.6% of women who saw a GO received stage-appropriate surgery. The percent of women with Stages IC-IV cancer who received both stage-appropriate surgery and multiagent chemotherapy increased significantly from 31% in 2002 to 38% in 2011. From 2002 to 2011, 2-year cause-specific ovarian cancer survival did not improve for Stages I/II cancers, with slight improvement for Stages III/IV cancers. Conclusions: There has been modest improvement in the receipt of guideline care for women with ovarian cancer, 2002-2011. However, current treatment falls far short of clinical recommendations and may explain limited improvement in 2-year cause-specific survival. There has been a marked increase in the percent of women consulting a GO and seeing a GO increased the chances of receiving guideline care. However many women who consulted a GO did not receive guideline care. There needs to be a better understanding of the decision-making process about treatment during the consultation with GOs and other factors precluding receipt of guideline care.
Comparison of patient reported symptom burden in patients with ovarian cancer undergoing primary vs. interval tumor reductive surgery.
Authors: Meyer Larissa , Shi Qiuling , Iniesta Maria , Harris Melinda , Sun Charlotte C. , Lasala Javier , Wang Shelley , Nick Alpa Manchandia , Lu Karen H. , Ramirez Pedro T 
Published: September 2018

5557 Background: Patient-reported outcomes (PROs) are important in comparative effectiveness research. We compared symptom burden and functional recovery in pts undergoing primary cytoreductive surgery (PCS) or neoadjuvant chemotherapy (NACT) and interval cytoreductive surgery (ICS) within an enhanced recovery after surgery program (ERAS). Methods: Perioperative PROs were measured for women with ovarian cancer undergoing PCS or ICS using the MD Anderson Symptom Inventory- Ovarian Cancer, a 27-item validated tool which was administered preoperatively, daily in hospital, and at least weekly for 8 weeks post-op. Mixed-effect modeling was performed. Results: 108 pts (45 PCS, 63 ICS) participated. There was no difference in median age, Charlson comorbidity index, ASA status, history of chronic opioid use, length of stay or readmission rate. At pre-op baseline assessment, the mean pain score was higher in the PCS group (3.8 vs. 1.8, p = .0005). ICS pts had a lower median surgical complexity score (4.0 vs. 2.0, p = .03), and shorter median surgical time (260 min vs. 223 min, p = .05). During hospitalization, pts undergoing PCS reported significantly more bloating, urinary urgency, distress, sadness and mood disturbance. Women who received NACT had a significantly higher symptom burden of neuropathy, leg cramps and memory disturbances. There was no difference in pain, fatigue, drowsiness, nausea, or emesis within the first 5 days postoperatively. While there was no significant differences in the physical interference composite score, (walking, work, activity), those who underwent ICS had improved affective interference scores (mood, relations, enjoyment of life). Conclusions: Within an ERAS program, there were few significant differences in surgery related symptoms related to physical recovery between pts undergoing PCS or ICS. The differences in overall symptom burden suggest that disease related symptoms (pain, bloating, urinary urgency) and emotional symptoms may be related to recent diagnosis and higher tumor burden in pts undergoing PCS while the increased numbness, leg cramps and memory issues reflect chemo-related effects in the ICS cohort.
Hedgehog inhibition impaired platinum response in high-grade serous ovarian cancer harboring high hedgehog ligand expression and mTOR pathway activation.
Authors: Ho Gwo Yaw , Lieschke Elizabeth , Kyran Elizabeth , Shield-Artin Kristy , Kondrashova Olga , Barker Holly , Hollian Robert , Cazet Aurelie , Phuong Thuan , Swarbrick Alex , McNally Orla , Bowtell David , Wakefield Matthew , Scott Clare L. 
Published: September 2018

5583 Background: Elevated Glioma-associated Oncogene Homolog-1 (Gli1) protein expression is associated with Hedgehog (Hh) pathway activation in high-grade serous ovarian cancer (HGSOC). Inhibition of Hh signaling in Gli1-overexpressing HGSOC patient-derived xenograft (PDX) inhibited tumour growth, particularly in combination with chemotherapy. Early phase HGSOC clinical trials of vismodegib, a potent Hh inhibitor (SMO inhibitor), were disappointing. We identified a HGSOC PDX harboring both Indian Hh ligand-overexpression and bi-allelic deletion of TSC1, which latter event is reported to derepress the mTOR pathway, driving non-cannonical Gli1 expression. We explored the effect of vismodegib in combination with cisplatin or the mTOR inhibitor, everolimus, in this model. Methods: A cell-line was generated from the well-characterised PDX (identity confirmed by PDX-specific p53 mutation). In vitro response to vismodegib was assessed. qRT-PCR was performed to establish Hh-ligand and Gli1 expression with/without SMO inhibition. A PDX was generated from this cell-line and randomized to in vivo treatment with cisplatin, vismodegib, everolimus or vehicle alone, or vismodegib in combination with cisplatin or everolimus. Results: The HGSOC cell-line was sensitive to vismodegib in vitro (EC50 of 3.5µM) and qRT-PCR analysis revealed down-regulation of Hh-ligand and Gli1 expression following in vitro SMO inhibition, confirming on-target vismodegib activity. In vivo treatment with vismodegib or everolimus alone did not result in reproducible in vivo efficacy. The combination of vismodegib + everolimus caused short-lived responses in 3 of 6 mice. Strikingly, in vivo treatment with vismodegib in combination with cisplatin impaired median survival (19 days) when compared with cisplatin treatment alone (43 days; p = 0.039) due to rapid tumour progression. Conclusions: Combining chemotherapy with Hh inhibition in Hh ligand-overexpressing HGSOC PDX with mTOR pathway activation may be detrimental. These findings highlight the importance of an in-depth understanding of tumour biology in order to effectively combine therapeutic approaches.
Does treatment at a high volume center mitigate racial and ethnic disparities in ovarian cancer survival?
Authors: Cowan Renee A. , Tseng Jill , Palayekar Vinat , Gennarelli Renee L. , Abu-Rustum Nadeem , Chi Dennis , Long-Roche Kara C. , Brown Carol L. 
Published: September 2018

5584 Background: Population-based studies of women with advanced ovarian cancer report racial/ethnic disparities in access to high volume centers (HVCs), surgical outcomes after primary debulking surgery (PDS), and overall survival (OS). However, there is evidence that with equal utilization of expert ovarian cancer care, differences in survival dissipate. The objective of this study is to evaluate patients (pts) with advanced ovarian cancer who had PDS at a HVC to determine whether racial/ethnic disparities persist in surgical outcome and survival. Methods: With IRB approval, all pts with stages IIIB to IV high-grade ovarian cancer who underwent PDS from 1/2001-12/2013 were identified. Pts self-identified race/ethnicity as Non-Hispanic White (NHW), Non-Hispanic Black (NHB), Asian (A), or Hispanic (H) in the medical record. The main outcome measures were PDS <1cm residual and OS. A Cox proportional hazards model was used to compare OS by race/ethnicity. Pt and clinical factors, including age, income, BRCA status, BMI, ASA, grade, carcinomatosis, bulky abdominal disease, were adjusted for in the multivariate analysis. Results: 963 pts were identified: 851 NHW (88%); 43 A (4%), 34 H (4%), 28 NHB (3%), 7 Other (0.7%). Asian pts were younger at diagnosis (p<0.0001); there were no differences in other demographic or clinical characteristics among racial/ethnic groups. After adjusting for pt and clinical factors, the likelihood of PDS to residual <1cm was similar among NHB and H compared to NHW pts; Asian pts were more likely than NHW to have >1cm residual (OR 2.32, 95%CI 1.1-4.9, p=.03). Median OS was 55.1 mos (95%CI: 51.8-58.5) for the entire cohort. On both univariate and multivariate analysis, there was no disparity in OS among racial or ethnic groups (p=0.615). Conclusions: Racial and ethnic disparities in overall survival and surgical outcomes in women with advanced ovarian cancer can be reduced by treatment at a HVC. Additional research is needed to determine what factors are associated with receiving treatment at HVCs, and what interventions could increase the diversity of patients treated at HVCs.
Role of adjuvant chemoradiation in treatment of elderly women with advanced high-grade endometrial cancer: A SEER-Medicare analysis.
Authors: Park Hyo K. , Ruterbusch Julie J. , Cote Michele L. 
Published: September 2018

5589 Background: Use of combined adjuvant chemoradiation (CRT) in treatment of advanced stage endometrial cancer is increasing, but the survival benefit over chemotherapy (CT) or radiation therapy (RT) alone remains unclear. We examined adjuvant treatment patterns and survival associated with CRT for Stage III-IV high-grade endometrial cancer using a large population-based database. Methods: Women 66 years of age or older who underwent primary surgical treatment for Stage III-IV high-grade endometrial cancer between 2000-2011 were identified from the SEER-Medicare database. Demographic and clinical predictors for receipt of adjuvant CRT vs. CT or RT alone were examined using multinomial logistic regression. In addition, overall survival (OS) by adjuvant treatment type, histology (endometrioid vs. non-endometrioid), stage, and age group were examined using Kaplan-Meier estimates and Cox proportional hazards regression. Results: Of the 2,735 eligible women, 13.1% received CRT vs. 42.5% CT alone vs. 13.2% RT alone, and 31.1% received no adjuvant treatment. Hispanic ethnicity, carcinosarcoma, serous histology, and Stage IV disease were significant predictors of receiving CRT over CT alone. Increasing age group, non-Hispanic black race/ethnicity, endometrioid histology, having 3+ comorbidities at the time of surgery, and not being partnered were associated with receiving RT alone over CRT. For Stage III disease, those who received CT (HR 1.30; 95% CI 1.09-1.55) or RT alone (HR 1.34; 95% CI 1.09-1.64) had poorer 5-year OS compared to CRT. In a subgroup analysis, the relative survival benefit of CRT vs. CT was only significant for women < 75 years of age and was more pronounced for endometrioid (HR 1.72; 95% CI 1.22-2.41) vs. non-endometrioid histology (HR 1.22; 95% CI 0.99-1.49). For Stage IV disease, there was no survival difference among those who received CT or RT only compared to CRT regardless of histologic subtypes. Conclusions: Adjuvant CRT was associated with improved OS in elderly women with Stage III high-grade endometrial cancer. This survival benefit was more pronounced for endometrioid histology and women < 75 years of age.
Effect of neoadjuvant pertuzumab-containing regimens on pathologic complete response rates in stage II-III HER2-neu positive breast cancer: A retrospective, single institutional experience.
Authors: Murthy Rashmi Krishna , Fujii Takeo , Hess Kenneth R. , Raghavendra Akshara Singareeka , Lim Bora , Barcenas Carlos Hernando , Zhang Hong Amy , Chavez-Mac Gregor Mariana , Mittendorf Elizabeth Ann , Litton Jennifer Keating , Giordano Sharon Hermes , Thompson Alastair Mark , Valero Vicente , Tripathy Debu , Ueno Naoto T. 
Published: September 2018

580 Background: Pertuzumab (P) in combination with trastuzumab (H) based chemotherapy is currently FDA- approved as a standard neoadjuvant treatment for patients with clinical stage II-III HER2-positive (HER2+) breast cancer (BC). The chemotherapy backbone of HER2-targeted therapy varies and may include taxane (T) and/or anthracycline (A), or carboplatin (C). The goal of this study was to retrospectively evaluate the pathologic complete response (pCR) rate for HP-containing regimens compared to H containing regimens for stage II-III HER2+ BC. Methods: We identified all patients (n = 1150) with stage II-III HER2+ BC who received neoadjuvant HER2-targeted therapy from 2005 to 2016 through an institutional database. All patients underwent primary breast and lymph node surgery. pCR was defined as ypT0/is, ypN0. Univariate/multivariate logistic regression and chi-squared test for comparing proportions was used for the statistical analysis. Results: pCR was significantly higher for the HP group (n = 200) compared to the H group (n = 950): 44% vs. 41%, odds ratio = 1.8 (95% CI = 1.3, 2.5; P = 0.0002). Even with adjustment for all clinically significant factors (age, stage, tumor grade, hormone receptor (HR) status, A or C exposure), the improvement was statistically significant (adjusted OR = 2.1 (95% CI = 1.5, 2.9; P < 0.0001). The pCR rate by stage and HR status for the HP group is 62% vs. 55% (stage II vs. III) and 71% vs. 51% (HR- vs. HR+). The effect of P was not modified by HR status (HR-, OR = 2.3; HR+, OR = 1.7, P = 0.39) or by A (A-yes, OR = 1.8; A-no, OR = 2.6) (P = 0.28 for interaction) or C (C-yes, OR 2.6; C-no, OR = 1.8) (P = 0.30 for interaction). P was significantly more likely to be given to patients without A (36% vs. 10%, P < 0.0001) and more likely to be given to patients with C (30% vs. 14%, P < 0.001). In both groups, significant predictors of pCR were found to be stage, HR status, and C exposure. Conclusions: Pertuzumab containing regimens yield higher pCR rates compared to non-Pertuzumab containing regimens in stage II- III HER-2 positive breast cancer. The effect of Pertuzumab is not modified by anthracycline or carboplatin use.
Developing and validating a multivariable predictive biomarker for treatment selection for oropharyngeal squamous cell carcinoma: The PREDICTR-OPC study.
Authors: Mehanna Hisham Mohamed , Haider Syed , Rapozo Davy Carlos , . von Zeidler Sandra , Harrington Kevin , Winter Stuart , Jones Terence , Pring Miranda , West Catharine , Golusinski Pawel , Sloan Philip , Thavaraj Selvam , Odell Edward William , Hunter Keith , Shah Ketan A , Thomas Gareth , Robinson Max 
Published: September 2018

6004 Background: To date there are no validated predictive tests to inform treatment selection for patients with oropharyngeal cancer (OPC). Currently treatment is decided on disease resectability, clinician preference and patient choice. Methods: Objective To develop a predictive test to select treatment for advanced OPC. Participants Training cohort: 543 cases from 10 cancer centres. External validation cohort: 442 cases from 3 centres. Design Multivariable logistic regression of 8 clinical parameters and 10 biomarkers to develop biomarker-only and composite clinical/biomarker predictive models; subsequently validated on a separate cohort. Biomarkers scored by ≥2 ‘blinded’ pathologists. Outcomes Primary: overall survival (OS). Results: 724 males, 261 females; Median follow-up =8.8 (6.86-10.47) years. More validation cases received surgery (53.5% vs 37.9%, p=0.001) and fewer received chemo/radiotherapy (42%vs67.5%; p=0.001) compared to training cohort. The biomarker-only model performed better than the clinical/biomarker one. The final OS model - comprising p16, high risk HPV DNA ISH, survivin and tumour infiltrating lymphocyte score (TILS)- was not only prognostic for OS, but importantly was predictive for surgery+/-adjuvant RT over CRT (3yr OS 63%, vs 42.5% respectively) in the High Risk group. Treatments were equally effective in the Low Risk group. The RFS model (p16, PLK1, survivin, TILS) was prognostic, but not predictive for treatment. Validation testing confirmed good calibration and concordance (C-index =0.73; 0.68-0.79). The OS model remained prognostic and predictive for surgical treatment in High Risk group (HR=0.51; 95%CI= 0.3-0.85, p=0.01). Conclusions: To our knowledge, this is the first-ever validated model for treatment selection in HNC. Clinicians can now recommend the treatment most likely to be effective on the basis of an easily-applied, relatively inexpensive panel of 4 biomarkers. [Table: see text]
Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: A phase III multicentre randomised controlled trial.
Authors: Chen Ming-Yuan , Cao Su-Mei , Yang Qi , Guo Ling , Mai Hai-Qiang , Mo Hao-Yuan , Cao Ka-Jia , Qian Chao-Nan , Zhao Chong , Yanqun Xiang , Zhang Xiu-Ping , Lin Zhi-Xiong , Li Wei-Xiong , Guo Xiang , Hong Ming-Huang 
Published: September 2018

6005 Background: The role of neoadjuvant chemotherapy (NACT) for locoregionally advanced nasopharyngeal carcinoma (NPC) is unclear. We aimed to evaluate the feasibility and efficacy of NACT followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in locoregionally advanced NPC. Methods: Patients with stage III-IVB (excluding T3N0-1) NPC were randomly assigned to receive NACT followed by CCRT (investigational arm) or CCRT alone (control arm). Both arms were treated with 80 mg/m² cisplatin every three weeks concurrently with radiotherapy. The investigational arm received cisplatin (80 mg/m² d1) and fluorouracil (800 mg/m² civ d1-5) every three weeks for two cycles before CCRT. The primary endpoint was disease-free survival (DFS) and distant metastasis-free survival (DMFS). Secondary endpoint was overall survival (OS). Results: 476 patients were randomly assigned to the investigational (n = 238) and control arms (n = 238). The investigational arm achieved higher 3-year DFS rate (82.0%, 95% CI = 0.77-0.87) than the control arm (74.1%, 95% CI = 0.68-0.80, P = 0.028). The 3-year DMFS rate was 86.0% for the investigational arm versus 82.0% for the control arm, with marginal statistical significance (P = 0.056). However, there were no statistically significant differences in OS or locoregional relapse-free survival (LRRFS) rates between two arms (OS: 88.2% vs 88.5%, P = 0.815; LRRFS: 94.3% vs 90.8%, P = 0.430). The most common grade 3–4 toxicity during NACT was neutropenia (16.0%). During CCRT, the investigational arm experienced statistically significantly more grade 3–4 toxicities (P < 0.001). Conclusions: NACT improved tumor control compared with CCRT alone in locoregionally advanced NPC, particularly at distant sites. However, there was no early gain in overall survival. Longer follow-up is needed to determine the eventual therapeutic efficacy. Clinical trial information: NCT00705627.
Validation of the pathological classification of lymph node metastasis for head and neck tumors (HNSCC) according to the 8th edition of the TNM Classification of Malignant Tumors (8th TNM).
Authors: Lopez-Pousa Antonio , Garcia Jacinto , Lopez Montserrat , Bague Silvia , Granell Esther , Lopez Vilaro Laura , Farre Nuria , Majercakova Katerina , Fernández Alejandro , Gallego Rubio Oscar , Barba Andrés , Andrés Marta , Gomila Paula , Del Carpio Huerta Luis Paul , Virgili Ana , Quer Miquel , Sullivan Ivana GABRIELA , Leon Xavier 
Published: September 2018

6014 Background: Changes in 8th TNM edition are a specific staging for p16+oropharyngeal carcinoma and the inclusion of extracapsular spread (ECS) in N extension. We evaluate the improvement in prognostic capacity from the inclusion of the ECS in HNSCC patients treated with a neck dissection (ND). Methods: Retrospective study based on prospectively collected information of 1188 HNSCC patients (oral cavity, HPV-oropharynx, hypopharynx, or larynx) diagnosed from 1990 to 2013, treated with unilateral or bilateral ND and a minimum fw-up of 2 years. We performed 1820 ND: 410 radical, 1410 selective ND; 683 patients (60.1%) had bilateral ND. Mean lymph nodes/patient: 32.6 (SD 19.9, 7-118). In 157 cases (13.8%) ND was performed after radiotherapy (RT, n =71) or chemoradiotherapy (CHRT, n = 86) with a median interval of 8.5 weeks (6-10). 596 patients (52.4%) had postoperative RT (n=525) or CHRT (n=71). Mean fw-up: 5.6 years (SD 4.9): 213 patients (18.7%) had local failure, 158 (13.9%) regional failure, 172 (15.14%) metastases. Results: 570 patients (50.1%) had lymph node metastases, 288 (50.5%) with ECS. The 8th TNM produced upstaging of 20.9% of pN1 patients to pN2a (n=33), and of 58.4% of the patients classified as pN2 to pN3b (n=220). The 7th TNM Classification (7thTNM), 5-year cause-specific survival for pN2 (35.5%) was similar to pN3 (21.6%). In the 8th TNM, 5-year cause-specific survival for pN2 (53.3%) sits in an more intermediate position between pN1 (70.5%) and pN3 (24.0%). Five-year cause-specific survival for pN2 patients with ECS (n=217) was 22.4%, and for patients without ECS (n=157) was 51.4%. There were statistically significant differences in survival between the two reclassified groups (P=0.0001). pN1 patients in the 7thTNM did not show survival differences when stratified by the presence of ECS: 5-y SV: 63.5% for ECS (n=33), 70.5% for non-ECS (n=125) (p=0.838). Conclusions: Inclusion of ECS in the pathological classification of the 8th TNM Classification edition improved the prognostic capacity, as compared with the previous version, basically produced by the migration of 58.4% of pN2 in the 7th TNM to the new pN3b category