bluuebunny/crossref_metadata_2025_split huggingface dataset:
A retrospective analysis of lymph node status in advanced ovarian, fallopian, and peritoneal cancer.
Authors: Itani Yoshio , Morita Sayuri , Sugimoto Hitomi , Takeda Yoshiki , Sasaki Yoshikazu , Ishibashi Satoko , Shugiura Atsushi , Hirano Hitoshi , Toyoda Shinji , Kita Tsunekazu 
Published: September 2018

e17074 Background: The purpose of this study was to assess lymph node (LN) status; greatest dimension (D), D of metastatic LN (LN (+)) foci (MF), number of LN (+) of each patient, and MF area aggregated in each patient affected by LN metastasis in FIGO stage III and IV ovarian, fallopian, and peritoneal cancer. Methods: We researched the consecutive 25 patients who underwent primary debulking surgery or neoadjuvant chemotherapy (NAC) followed by interval debulking surgery including systemic lymphadenectomy from 2004 to 2015. Non-serous histology was 20 % (5/25). LN (+) were detected in 12.6% (169/1344) of lymph node preparations. Results: The patients’ median age was 53 years. Median number of LN (+) and sum of MF area in each patient were 2 (range 0-37) and 2 mm2 (range 0- 498). Mean D of the entire LN and of the MF were 4.7mm (95%Confidence Interval (CI); 4.5,4.9) and 6.1mm(95% CI; 5.2, 7.0). The LN (+) displayed a significantly larger mean D value (7.9 mm, 95% CI: 7.4, 8.5) than the non-metastatic lymph nodes (LN (-)) (4.2 mm, 95% CI: 4.0, 4.4) (p<0.05; student t test). D of MF (mm) was approximated by LN (+) area (mm2) as follows; (D of MF) = 2.58+ 0.094*(LN (+) area)+ 0.062* ( ( LN (+) area)-43.2)2; R2=0.75; p<0.0001. The D of MF with NAC, 5.0 mm (95%CI: 3.6, 6.4) demonstrated smaller than that without NAC, 7.0 mm (95%CI: 5.8, 8.1) (p<0.05; student t test). The proportion of LN (-) patients was significantly higher in the NAC group (44%, 4/9) than in the non-NAC group (6%, 1/16) (p=0.022). D of LN (+), D of MF ≥10 mm, sum of MF area, and number of LN (+) ≥ 2 did not achieve statistical significance in analysis with the relative risk (RR) of death. Conclusions: LN (+) exhibits larger D than LN (-) and D of MF could be estimated by LN (+) area. Some MFs shrink after NAC, and hence, become difficult to detect pathologically. In advanced ovarian, fallopian, and peritoneal cancer LN size and sum of MF area could not show an impact on prognosis.
Clinical relevance of circulating tumor cells in ovarian, fallopian tube and peritoneal cancer.
Authors: Gebauer Gerhard , Banys-Paluchowski Malgorzata Joanna , Neubauer Hans , Krawczyk Natalia , Kaczerowski Anna , Paluchowski Peter , Meier-Stiegen Franziska , Abdel-Kawi Ahmed , Fehm Tanja N. 
Published: September 2018

e17080 Background: Presence of circulating tumor cells (CTCs) in peripheral blood is associated with impaired clinical outcome in a variety of cancers. So far, limited data are available on the significance of CTCs in gynaecological malignancies. Aims of the present study were to evaluate the dynamics of CTCs in patients with ovarian, fallopian tube and peritoneal cancer during chemotherapy and to assess the clinical relevance of these changes. Methods: 38 patients with ovarian (n=31), fallopian tube (n=4) and peritoneal (n=3) cancer were included into the study. All patients received chemotherapy in the first-line setting (n=19) or tumor recurrence (n=19). CTC analysis was performed prior to systemic treatment, after three and six cycles of chemotherapy and analysed using CellSearch system (Veridex). A tumor cell was defined as EpCAM+, cytokeratin+, CD45-, and positive for the nuclear stain DAPI. CTC positivity was defined as detection of at least one CTC per 7.5 ml blood. Results: 11 out of 38 (29%) patients were CTC positive at baseline. Positivity rate was 20% in patients with first-line setting and 37% in those with tumor recurrence. 1of the 4 patients with fallopian tube cancer presented with CTCs in contrast to 1 out of 3 patients with peritoneal cancer and 10 out of 31 ovarian cancer patients. Presence of CTCs was not correlated with other prognostic factors, such as the FIGO stage, nodal status, or grading. CTC positivity declined to 8% after three cycles of cytotoxic therapy and no patient was CTC positive after 6 cycles of chemotherapy. 12 patients died during follow-up. Patients with CTCs at baseline had significantly shorter overall survival compared with CTC negative patients (p = 0.002; mean OS 5.8 [95%-CI 2.7-8.9] vs. 15.2 [10.5-19.8] months, median OS 3.0 [1.4-4.6] vs. not reached). In the subgroup of patients with primary cancer, CTC positivity was significantly associated with overall survival in the univariate analysis (p = 0.008). Conclusions: Hematogenous dissemination of single tumor cells is a common phenomenon in ovarian, fallopian tube and peritoneal cancer. Patients with CTCs in the peripheral blood at time of diagnosis are more likely to die than those who are CTC-negative at baseline.
What are the expectations and preferences of patients with ovarian cancer to a maintenance therapy? A NOGGO/GCIG/ENGOT-ov22 survey (Expression IV) in 2101 patients.
Authors: Rohr Irena , Keller Maren , Chekerov Radoslav , Oskay-Özcelik Gülten , Richter Rolf , Heinrich Michaela , Taskiran Cagatay , Joly Florence , Wolfrum-Ristau Pia , Gornjec Andreja , Vergote Ignace , Achimas Patrick , Lorusso Domenica , Maenpaa Johanna Unelma , Sehouli Jalid 
Published: September 2018

e17096 Background: The primary aim of the survey was to investigate the expectations of European patients about maintenance therapy. Methods: A 24-item questionnaire was provided to ovarian cancer patients via internet or paper-version in9 European countries (Austria, Belgium, France, Germany, Italy, Romania, Slovenia, Finland and Turkey). Data was captured about demographics, tumor stage and therapy after first line and/ or recurrent disease and particularly about preferences of administration and expectations concerning a maintenance therapy. Results: Overall, 2101 questionnaires of ovarian cancer patients were evaluated. Over 63% of the patients were between 51 and 70 years (range 18-90). The majority of the patients were FIGO stage III at their primary diagnosis. 96% of the patients had a surgery and 93% received a chemotherapy. 38% of respondents had recurrent disease. 45% of the patients had already heard of and 29% received maintenance therapy. 85% of the patients heard about maintenance therapy from the doctor and 10% from other patients and 9% read about it on the internet. The four most disturbing side effects of maintenance therapy were polyneuropathy (37%), nausea (36%), loss of hair (34%) and vomiting (34%). The main objective of maintenance treatment for all patients was to increase the chances of cure (73%), followed by an improvement in the quality of life (47%) and the delay of tumor growth (37%). Many patients are willing to take a maintenance therapy until tumor progression (38%). 39% of the patients would prefer an oral administration and 29% do not have any preference for any specific administration. When we performed cross country sub-analysis between patients with primary diagnosis and relapse, or sub-analysis between patients who are actually receiving maintenance therapy or not, we observed no significant differences of expectations to a maintenance therapy. Conclusions: There is an urgent need for more information regarding side effects and treatment goals of maintenance therapy to avoid misunderstandings by the patient. This information may increase patient’s compliance for maintenance therapy in ovarian cancer.
Effect of older age and comorbitities on outcomes with neoadjuvant chemotherapy (NAC) for epithelial ovarian cancer (EOC).
Authors: Xu Zhaomin , Justiniano Carla Francesca , Becerra Adan Z , Aquina Christopher Thomas , Boscoe Francis P. , Schymura Maria J. , Fleming Fergal J. , Temple Larissa K. F. , Morrow Gary R. , Minasian Lori M. , Temkin Sarah Madhu 
Published: September 2018

e17101 Background: Although a survival benefit for NAC has not been shown in the overall population of EOC, some patients may benefit from NAC. This analysis evaluates the role of age and comorbidities on the effect of NAC compared to upfront surgery on survival among EOC patients in New York. Methods: Patients who underwent surgery for stage II-IV EOC from 2006-2013 were included from the New York State Cancer Registry and the Statewide Planning and Research Cooperative System. Elderly age was defined as >70 years. Comorbidity burden was defined with the Charlson Comorbidity Index (CCI). Cox models were used to examine the effect of NAC on 5 year overall survival. The analysis was then stratified by age and comorbidity score to evaluate the role of NAC in specific subgroups. Results: 4617 patients met inclusion criteria of which 25% were elderly and 11% received NAC. Factors associated with receipt of NAC included age > 70, advanced stage, serous histology and high hospital volume (p<0.01). After adjustment for patient, hospital, and surgeon characteristics, NAC was associated with a 27% (p<0.01) increase in 5 year overall mortality in all EOC patients. Among the elderly, NAC did not have a significant effect on overall (p=0.47) or EOC-specific survival (p=0.24). Elderly and non-elderly women without comorbidities had a higher risk of death with NAC than primary surgery. There was a trend towards improved survival among elderly patients with higher comorbidity scores. (Table) Conclusions: The impact of NAC on EOC survival differs dependent on age and comorbidities. Patients with no comorbidities may have better prognosis with upfront surgery. Counterintuitively, those with more comorbidities, particularly the elderly, may derive survival benefit from upfront neoadjuvant therapy. [Table: see text]
18FDG-PET/CT for the detection of residual/recurrent in patients with head and neck cancer: A systematic review and meta-analysis.
Authors: Shang Jinbiao , Gu Jialei , Wang Wendong , Wang Kejing , Xu Yaping 
Published: September 2018

e17502 Background: To evaluate the diagnostic accuracy of positron emission tomography (PET) and PET/computed tomography (CT) for detecting residual and/or recurrent local and regional disease in patients with head and neck cancer (HNC) following radiotherapy with or without chemotherapy. Methods: Studies about 18FDG-PET/CT for detecting residual or recurrent disease after treatment in patients with HNC were systematically searched in the MEDLINE and EMBASE databases. The Stata software was used to obtain pooled estimates of sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio for 18FDG-PET/CT. Results: 31 articles bulled all inclusion criteria. The pooled sensitivity and specificity of PET and PET/CT for detecting residual or recurrent disease at the primary site was 88.7% and 89.6%, respectively. For residual or recurrent neck disease, the sensitivity and specificity were 75.9% and 92.0%, while for residual or recurrent localregional disease, the values were 89.6% and 87.8%. Conclusions: 18FDG-PET/CT has good diagnostic performance for the detection of residual and/or recurrent in HNC patients.
Co-targeting mTORC and EGFR signaling as a therapeutic strategy in HNSCC.
Authors: Swick Adam D , Prabakaran Prashanth Jyothi , Miller Margot , Javaid Amal M , Fisher Michael , Sampene Emmanuel , Ong Irene , Iida Mari , Nickel Kwang-Ok P , Bruce Justine Yang , Wheeler Deric , Kimple Randall J. 
Published: September 2018

e17509 Background: Head and neck squamous cell carcinomas (HNSCCs) are frequently altered along the PI3K/AKT/mTORC signaling axis leading to development of therapeutics targeting this pathway. Despite excellent preclinical data, the use of these compounds as monotherapy has been underwhelming in initial clinical trials and identification of predictive biomarkers remains challenging. The EGFR monoclonal antibody cetuximab remains the only approved targeted agent for HNSCC and has potential use in combination therapy. Methods: Both catalytic mTORC (AZD8055) and PI3K/mTORC(NVP-BEZ-235) inhibitors were tested +/- cetuximab in a panel of HNSCC cell lines and patient derived xenografts (PDX) evaluated for potential biomarkers of PI3K/AKT/mTORC pathway. Cell lines were assayed for response to all three agents by multiple approaches, and confirmed by siRNA knockdown. Five PDX models that presented PIK3CA mutation or intrinsic cetuximab resistance were treated with a combination of cetuximab and AZD8055. Results: In HNSCC cells no likely sensitizing mutations were identified, whereas putative protein biomarkers were elevated in some lines. All lines showed similar response to both PI3K/mTORC and dual mTORC inhibition with cetuximab combination producing modest additive effect with similar results for siRNA knockdown. In PDX models, in vivo single agent mTORC inhibition inhibited growth of a PIK3CA mutant cancer, but had little effect on any PIK3CAWT or a second PIK3CA mutant model. In all models the combination therapy showed greater growth delay than monotherapy. Conclusions: The uniform ability of PI3K and mTORC inhibition to suppress the growth of HNSCC cells highlights the pathway’s role in driving proliferation. In vivo, despite some PDX models meeting likely selection criteria, the single agent therapy was largely ineffective. Conversely improved response of combination treatment suggests the potential for adding a catalytic mTORC inhibitor to cetuximab therapy. Overall, these results add to a growing body of evidence suggesting approaches that attempt to match biomarkers to the optimal therapy in HNSCC remains complex and challenging.
Impact of tobacco and alcohol use on HRQOL in patients with advanced head and neck cancer: Results from a community oncology database.
Authors: Fisher Maxine D. , Fernandes Ancilla , Olufade Temitope O , Miller Paul J. , Walker Mark Stephen , Fenton Moon Jung 
Published: September 2018

e17512 Background:Tobacco and heavy alcohol use are important risk factors for head and neck (H&N) cancer. H&N cancer may affect activities of daily life (eg, eating, drinking, swallowing), and can be debilitating to health-related quality of life (HRQOL). This study reports HRQOL findings for patients (pts) with advanced H&N cancer eligible for systemic treatment in multimodality or palliative care. Methods:Medical records from pts diagnosed 1/1/2007–10/1/2015 with stage III–IVc H&N cancer and ≥1 disease progression were retrospectively collected from 10 US community oncology practices. We evaluated specific items and composite measures (physical symptoms, treatment effects, distress, despair, ambulation, and performance) with the Patient Care Monitor (PCM), an 86-item pt-recorded outcomes survey. Linear mixed models (LMM) assessed prespecified effects (eg smoking, alcohol use) and change over time across 2 lines of therapy. Results: The study included 462 pts (median age, 61 y; range, 26–99 y). Of these, 81% were male, 77% white, and 21% African American. The most common tumor locations were hypopharynx/larynx (31.1%) and oropharynx (30.9%). Overall, 41.8% of pts were current tobacco users and 22.3% were current or past alcohol abusers/excessive users. No significant difference was observed for receipt of surgery or radiation therapy in the first or second line for either alcohol or tobacco use. Approximately 1240 PCM surveys were collected from 146 pts. LMM showed effects for past tobacco use vs never/undocumented use for sore throat (1.31), dry mouth (1.46), and changes in taste (1.57); P< 0.05. Effects were seen for alcohol use for increased trouble swallowing (1.87; P= 0.01) among current or past abusers/excessive vs never/undocumented users. LMM showed no impacts of tumor location. Models of composite scores showed that after progression, worsening was seen over time for despair (0.57; P= 0.03), impaired ambulation (0.81; P= 0.05) and performance (0.66; P= 0.05). Conclusions: The study showed smoking and alcohol use were associated with worsening clinical symptoms in pts with advanced H&N cancer. Certain composite scores for symptom burden also worsened with progression.
PTEN loss as a predictive biomarker in head and neck squamous cell cancer (HNSCC) patients treated with cetuximab (C).
Authors: Eze Nnamdi , Chung Christine H. , Neumeister Veronique , Sandoval-Schaefer Teresa , Lee Ju-Whei , Burtness Barbara 
Published: September 2018

e17520 Background: No biomarker of C resistance has been identified in HNSCC. PTEN loss is present in approximately 30% of HNSCC. Biomarker analysis of the E5397 study suggested that addition of C to cisplatin in R/M HNSCC improves PFS in PTEN high/PIK3CA wild type patients but not those with PTEN loss or PIK3CA mutation. We hypothesized that PTEN testing may aid patient (pt.) selection for C therapy in HNSCC. Methods: MCC15780 was a phase II randomized trial of C plus sorafenib or C plus placebo in R/M HNSCC. 52/56 pts. in this study received C. PTEN analysis using AQUA as previously described was performed on tumor from 38 pts. Automated image capture was performed with HistoRx PM-2000 using the AQUAsition software. AQUA PTEN cut off determined as 1177 based on the first tertile.Fisher’s exact test used to compare low and high expression group. Event-time distributions estimated by Kaplan-Meier and compared using log-rank. Stratified Cox proportional hazards models used to estimate hazard ratios (HR) and test for significance for OS and PFS. All p-values are two-sided. A level of p < 0.05 is considered statistically significant. Results: 12/37 (32%) tumors were PTEN low. There was statistically significant improvement in PFS in PTEN high tumors compared to PTEN low tumors (HR (high/low) =0.33, 95% CI= (0.14, 0.75), p=0.008); and this remains significant after adjusting for age, sex, race, and ethnicity (HR (high/low) =0.27, 95% CI= (0.11, 0.67), p=0.004). Conclusions: PFS is significantly longer in PTEN high tumors compared to PTEN low tumors (HR=0.33, 95% CI= (0.14-0.75), p=0.008) in patients with R/M HNSCC treated with C. This finding remains significant after adjusting for age, sex, race, and ethnicity (HR=0.27, 95% CI= (0.11-0.67), p=0.004).This warrants PTEN analysis of specimens from larger cetuximab-based RCT. [Table: see text]
Prognostic value of pretreatment 18F-FDG PET-CT for nasopharyngeal carcinoma patients.
Authors: Huang Yecai , Feng Mei , He Qiao , Xu Peng , Lang Jinyi 
Published: September 2018

e17521 Background: Nasopharyngeal carcinoma (NPC) is a special subtype of head and neck cancer (HNC), there is no highly specific prognostic parameters for NPC. Prognostic value of pretreatment 18F-PET-CT in NPC patient has controversial conclusion. Methods: The prospective and retrospective observational trails which used the 18F-FDG PET to predict the prognosis of the NPC patients were searched in MEDLINE, EMBASE, Cochrane library, CBM, CNKI and VIP (inception to July 2016). Two authors independently assessed study quality and extracted data. Event-free survival (EFS) was considered as the primary endpoint and overall survival rate (OS) was considered as the secondary endpoint. Results: 14 studies and 1,134 patients were included in our analysis. The HR (Hazard ratio) of SUVmax-T, MTV-T and TLG-T for EFS was 1.71 (95% CI, 1.02-2.86, p= 0.04), 2.38 (95%CI 1.53-3.70, p= 0.0001) and 1.65 (95%CI 0.76-3.59, p= 0.21) respectively. Among studies including TLG-T, those with a fixed SUV of 2.5 had an HR 3.55 (95% CI, 1.42–8.84, p= 0.007). The HR of SUVmax-T and MTV-T for OS was 2.19 (95%CI, 1.47-3.27, p= 0.0001) and 2.69 (95% CI, 1.01-7.17, p =0.05). Among studies including MTV-T, those with a fixed SUV of 2.5 had an HR of 4.07 (95% CI, 2.22–7.46, p< 0.00001). Test for predictive value of pretreatment SUVmax-LN, MTV-LN and TLG-LN for EFS and OS showed no significant results ( p> 0.05). Conclusions: We suggested thatSUVmax, MTV and TLG (with a fixed SUV of 2.5) of primary tumor before treatment may be the independent prognostic factors for NPC patients, while SUVmax, MTV and TLG of metastatic lymph node are not.
Determination of the potential of detecting 3q gain as a valuable biomarker in the management of patients with human papilloma virus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC).
Authors: Hegde Upendra P. , Kershnar Eric , Dowsett Robert , Masternak Sophie , Verma Yogita , Tafas Triantafyllos , Kilpatrick Michael 
Published: September 2018

e17534 Background: The most recurrent structural chromosomal aberration in HPV associated cervical cancer is gain of the 3q26 locus testing of which has clinical utility in management of patients with cervical lesions. A significant proportion of OPSCC are HPV mediated, suggesting the possibility of a common disease mechanism. The objective of this study is to determine the potential clinical validity of assessing 3q gain as a biomarker in the management of patients with HPV associated OPSCC. Methods: An oral swab using a cytological brush was obtained of the region containing visualized tumor site in newly diagnosed HPV associated OPSCC patients following written informed consent of an IRB approved protocol at the University of Connecticut. The swabs were obtained at the diagnosis and serially after chemotherapy and/or chemo-radiotherapy as well as at 3 months after treatment completion. The specimens’ 3q gain status was determined by fluorescent in situ hybridization (FISH) analysis, utilizing robotic fluorescence microscopy for detection of rare cells demonstrating high 3q26 copy number Results: 54 specimens were collected from 13 patients, of which slides were prepared, hybridized and analyzed from 50. Data was not available in four specimens due to insufficient cells while for eight patients, multiple specimens were obtained before, during and after 3 months of treatment. Depending on the specimen’s cellularity, up to 170,969 cells were analyzed. Cells with > 4 copies of the 3q26 locus were detected in 32 of the 50 analyzable specimens. For several patients, the number of cells with more than four 3q26 signals detected in the later time points of treatment was lower than the number detected at diagnosis. Conclusions:This preliminary dataset demonstrates the ability to detect gain of the 3q26 locus in cells collected by cytological brushing of the region containing an OPSCC. The approach offers the possibility of a minimally invasive method to determine the 3q26 gain status as a reliable biomarker of HPV associated OPSCC that might have value in early diagnosis and management.