bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival impact of neoadjuvant treatment in cervical cancer stage IIB
Authors: Oliveira H. F. , Peria F. M. , Andrade J. M. , Marana H. R. , Santos A. C. , Mendonça L. M. , Elias J. 
Published: August 2020

e16559 Background: A few previous studies demonstrated that neoadjuvant chemotherapy, followed by preoperative radiotherapy in diagnosed IIB cervical cancer patients, had similar therapeutic results as the standard protocol with concurrent chemoradiotherapy, considering complete response; overall survival; disease free survival and toxicity; requiring its evaluation as an alternative approach. Methods: One hundred sixteen women with IIB stage cervical cancer stages were submitted to a platinum combined based neoadjuvant chemotherapy followed by chemoradiotherapy with cisplatin. Those who had a good response, allowing a surgical approach, underwent the Wertheim-Meigs procedure. Those that could not be submitted to surgery remained in clinical follow-up. Results: The age of the patients were 22 to 75 years old (48.7±11.4 years). The average follow-up was about 48 months (1–120). The good response to the neoadjuvant treatment was found in 76 patients (65.5%), and surgery was possible in 86 (74%). The pathological complete response was found in 39 (33%), and the partial response in 40%. The global recurrence was diagnosed in 37 (32%) patients. In the operated group (n = 86), the overall-five years survival was 76%, and in the non-operated group (n = 30) was 17,5%. The five years-global survival was 79,2% in “good response” (GR) patients, and 27.4% in that with “no-good response” (NGR) to combined neoadjuvant treatment ( p < 0.01). The free-relapse survival was 79.4% in GR, and 32.5% in NGR group (p < 0.01). Conclusions: Amongst the studied prognostic factors, the most important one for interval of relapse and survival (global and free-relapse) was a good response to the neoadjuvant treatment, and that this treatment had an acceptable toxicity and could be considered in other trials as an option to standard treatment. No significant financial relationships to disclose.
Behavior of borderline ovarian tumours (BOTs): Single institution experience
Authors: Oaknin A. M. , Romeo M. , Pons F. , Perez X. , Barretina P. , Vidal A. , Martí L. , Barahona M. , Germá J. , Ponce J. 
Published: August 2020

e16560 Background: To provide useful material for discussion, we report an analysis of a retrospective accrued, single-institution population with BOTs. Methods: 99 consecutive patients treated between April 1989 and July 2008, were reviewed for clinical characteristics, histology, surgical types, recurrence, and prognosis. Results: Median age was 46 years (19–77). 90% of patients were diagnosed by vaginal ultrasound as complex adnexal mass. CA-125 and CA19.9 was elevated in 60% and 30% of patients respectively. Primary treatment was surgery: laparotomy and laparoscopy (LT/LC) approach in 78% and 22% of patients, respectively. 33 patients (34%) underwent comprehensive staging operation; fertility-sparing surgery was performed in 18 patients (18%), and an incomplete staging in 47 patients (48%). The pathology results were: clear cell BOTs 1 case (1%); serous 42 cases (42.4%); mucinous in 56 women (56.6%) (46 intestinal/10 mullerian). 2 out of 56 mucinous BOTs were associated with pseudomixoma peritonei. Cyst-rupture was found in 22.5% and 38.9% of patients with LT/LC approach. 91women (93.8%) had stage I; 2 (2%) had stage II; and 6 (4.2%) had stage III disease. We identified 6 patients (7.8%) with noninvasive implants involving abdominal peritoneum (1), pelvic peritoneum (1), omentum (2) and both pelvic peritoneum and omentum (2). With a median follow-up of 3.6 years (0–18.4), we observed 5 recurrences (2 in contralateral ovary, 1 ipsilateral, 1 invasive peritoneal implant, and 1 para-aortic node). All were stage I disease at diagnosis. 2 out of 5 had incomplete staging, 3 had conservative surgery.3 cases were serous type. Histology recurrences were: 2 borderline, 2 invasive ovarian cancer, and 1 unknown. All patients underwent secondary cytoreduction achieving an optimal debulking in 4. Only one patient received chemotherapy. Two women died of intercurrent disease and 1 woman died of disease. The 5-year overall survival rate for entire cohort was 98.5% (95.6%-100%; CI95%). Conclusions: Our results confirm published data. Overall BOTs have an excellent prognosis. Proper staging is the cornerstone of treatment. Laparoscopy approach is associated with higher cyst rupture. Recurrences are more frequent after incomplete or conservative surgery. No significant financial relationships to disclose.
Outcome analysis of stage II and III cervical carcinoma: Importance of optimal radiation therapy
Authors: Diaz J. J. , Thomas Mr B. , Hernandez E. 
Published: August 2020

e16562 Background: The objective of our study was to conduct an outcome analysis of patients with stage II and III cervical cancer (CC) treated in our institution. We sought to asses the effectiveness and toxicity of carboplatin concomitant with pelvic irradiation and the importance of compliance with treatment. Methods: A retrospective chart review was conducted of all patients with stage II and III CC treated at Temple University Hospital from January 2001 to December 2006. Results: Forty-eight patients with stage II and III CC without radiographic evidence of extra-pelvic disease (IIA = 11, IIB = 15, IIIA = 4, IIIB = 18) were treated during the period under study. Four (8%) patients had adenocarcinoma and 44 (92%) had squamous cell carcinoma. Median age at diagnosis was 48.5 (range, 24–83) years. Median follow-up was 23 (range, 1–74) months. Nonsurgical therapy consisting of radiation (RT) with or without chemotherapy (CT) was offered to all patients. Nine patients (19%) received no CT, whereas 36 (75%) received weekly carboplatin (90 mg/m2) and 3 (6%) received weekly cisplatin (40 mg/m2). Median numbers of CT cycles was 5 (range, 1–7). Optimal dose of RT was defined as a minimal cervical dose exceeding 7000 cGy, point A dose of 8000–9000 cGy and treatment duration not exceeding 56 days. Only 21 (44%) patients received optimal RT. Only 2 patients treated with carboplatin had grade 3 or 4 toxicity. The 5-year progression free survival (PFS) and overall survival (OS) was 41% and 56%, respectively. The pelvic failure (PF) and distal failure (DF) were 38% and 26%, respectively. There were only 4 PF (19%) and 4 DF (19%) in the 21 patients who received optimal RT. The estimate of probability of 5-year pelvic failure rate in patients who received optimal therapy and patients who received suboptimal therapy was 23% vs. 48% (p = 0.2) . On subset analysis patients who received optimal RT had a better 5-year OS (72% versus 45%, p = 0.09). The most important predictor of optimal radiation was compliance with treatment plan. Conclusions: Optimal RT is crucial for successful treatment of advanced CC. Chemo-sensitization with carboplatin is effective and well tolerated. No significant financial relationships to disclose.
Effects of ascites on perioperative and postoperative outcome in epithelial ovarian cancer
Authors: Novetsky A. P. , Pua T. L. , Curtin J. P. 
Published: August 2020

e16567 Background: A third of epithelial ovarian cancer (EOC) patients (pts) present with ascites at the time of diagnosis. Though not universally accepted, ascites has been reported to be a poor prognostic factor. Our purpose is to study the effects of ascites on the peri and postoperative outcome in EOC patients undergoing cytoreductive surgery. Methods: 172 EOC pts were retrospectively evaluated to determine the prognostic significance of ascites. Pts were divided into two groups based on the presence of ascites defined in pre-operative CT scans as A, none/small, versus B, moderate/ large. Influence of ascites on peri- and post-operative characteristics such as estimated blood loss (EBL), rates of optimal cytoreduction, intensive care unit (ICU) admission, minor complications (infection, ileus/bowel obstruction, transfusion, wound separation, DVT/PE), major complications (death or readmission within 30 days) and length of hospital stay (LOS) were analyzed using Chi Square, multivariate linear and cox regression, where appropriate. Results: There was no significant difference in EBL between the two groups (p = 0.27). Pts in A were more likely to be optimally cytoreduced compared to B (96% vs 61%, p < 0.001). After controlling for stage, women in B were more likely to be admitted to the ICU, (OR 3.03 (95% CI: 1.05–8.71). The rates of major complication was higher for B (3% vs 10%) though this did not reach statistical significance (p = 0.06). Overall minor complications were greater for B than in A (64% vs 26%, p < 0.0001). After controlling for stage, LOS was 2.9 days longer in B (p = 0.02). 21 women received at least 3 cycles of neoadjuvant chemotherapy prior to cytoreduction. EBL, LOS and major complications were no different than those undergoing primary cytoreduction then adjuvant chemotherapy. Conclusions: Optimal management of EOC pts with ascites is uncertain. Pts with ascites are more likely to be suboptimally cytoreduced, have increased rates of complications and consume more healthcare resources (ICU admission and longer LOS). Though our numbers are small, patients who received neoadjuvant chemotherapy do not have any difference in peri-post operative characteristics, but were all optimally cytoreduced. No significant financial relationships to disclose.
The Ep-CAM: A potential candidate for diagnosis in ovarian cancer
Authors: Sawasaki T. , Katsube Y. 
Published: August 2020

e16571 Background: The purpose of this study was to examine the expression of splice variants of the Ep-CAM gene in normal ovarian epithelial tissue and ovarian carcinoma and further to associate the expression of Ep-CAM with clinicopathologic characteristics if such an association exists. Methods: Ep-CAM expression was examined by semiquantitative PCR in 122 ovarian tumors (92 adenocarcinomas, 10 low malignant potential (LMP) tumors, and 10 adenomas) and 10 normal ovaries. Results: In carcinomas as well as LMP tumors and adenomas, Ep-CAM mRNA expression was significantly elevated compared to that in normal ovary samples. Ep-CAM mRNA expression level in carcinomas was significantly elevated compared to that in adenomas and Ep-CAM mRNA expression level in advanced clinical stage diseases was significantly higher than that in early stage diseases in ovarian carcinomas. With regard to histological type, Ep-CAM mRNA expression level in mucinous adenocarcinomas was significantly higher than those in the other tissue subtypes. Conclusions: These features imply that Ep-CAM expression may play an important role in ovarian cancer development and progression, and this may be useful as a diagnostic marker. No significant financial relationships to disclose.
Hormonal treatment of metastatic endometrial stromal sarcoma
Authors: Terada K. Y. , Davis J. , Kitayama J. , Shimizu D. 
Published: August 2020

e16576 Background: Endometrial stromal sarcomas (ESS) traditionally have been classified as low grade or high grade based on mitotic activity and histologic appearance. High-grade tumors are currently referred to as undifferentiated uterine sarcomas and are not included in this series. ESS are known to have high expression of estrogen and progesterone receptors. This is a retrospective study of patients with metastatic ESS treated with hormonal therapy. Methods: Following approval by the institutional review board all patients diagnosed with ESS from 1987–2007 were identified. Clinical and demographic information were abstracted from the charts and all histologic materials were re-reviewed. Estrogen and progesterone receptor testing was performed utilizing mouse monoclonal antibodies and the Cell Analysis Systems 200 Image analyzer. Survival was calculated using the Kaplan-Meier method and comparisons utilized the log rank test. Results: Thirteen patients with ESS were identified during this period. Seven had disease confined to the uterus. Six had extrauterine disease; 5 patients presented with metastases and 1 patient presented with a pelvic recurrence 20 years following a hysterectomy. All underwent surgical resection except for 1 patient that declined surgery. All 6 patients with metastases had tumors that tested positive for estrogen and progesterone receptors; all were treated with megestrol acetate initially for a period of 1–4 years. Two patients were then changed to maintenance with medroxyprogesterone acetate. Three patients with persistent disease were changed to aromatase inhibitors; 1 to letrozole and 2 to anastrazole. One of these patients has had a complete response and 2 have had stable disease. One patient has been lost to follow-up. Follow-up for the 6 patients was 2–22 years; no known patients died of their disease. Actuarial 2- and 5-year survivals were 80% and 65%, respectively. There was no significant difference in survival between patients with metastases and without metastases. Conclusions: ESS tumors are relatively uncommon and there is an absence of studies to guide treatment of patients with metastases. This experience indicates that these tumors respond well to hormonal manipulation. Treatment with progestins or aromatase inhibitors may result in remission or stable disease. No significant financial relationships to disclose.
Inhibition of human head and neck squamous cell cancer growth by modulation of heat shock proteins and induction of the mitochondrial apoptotic pathway with withaferin A
Authors: Cohen M. S. , Timmermann B. N. , O'Donnell G. , Samadi A. K. 
Published: August 2020

e17003 Background: Epithelial cancers, particularly lung cancer and head and neck squamous cell carcinoma (HNSCC), continue to pose formidable challenges in clinical practice. Novel chemotherapeutic agents have been developed, but even those have limited long-term benefits in the treatment of these tumors, illustrating the need to continue to improve systemic therapy for affected patients. The objective of the present study was to investigate the effect of withaferin A (WA), a plant-derived small molecule, on cancer cell growth, heat shock protein expression and induction of apoptosis in human HNSCCs. Methods: MDA1986 and JMAR HNSCC cells were used in all experiments. The effect of WA on cell viability was determined by MTS assay. Apoptosis and mitochondrial membrane potential changes were assessed by annexin V/propidium iodide and JC-1 staining respectively using standard flow cytometry methods. Effect of WA on modulation of heat shock proteins was determined by Western blot analysis. Results: Withaferin A reduces cell viability in both MDA1986 and JMAR cells with IC50 levels of 265 ± 5 nM by MTS assay, which is 5 fold higher than its reported activity in breast cancer cells. WA completely down-regulates HSP90beta, GRP94, and TRAP-1 expression at 250 nM concentration in HNSCC cells at 24 hours treatment. In addition, WA markedly increased HSP70 levels and mildly increased HSP27 levels in a dose-dependent manner at 24 hours treatment. Flow cytometry with Annexin V/PI staining shows that 5 μM WA treatment for 24 hours induced apoptosis in 63% of MDA1986 and 60% of JMAR cells. WA at 5 μM also reduced mitochondrial membrane potential by JC-1 staining with flow cytometry to less than 10% of controls in both JMAR and MDA1986 cells at 24 hours treatment. Conclusions: Withaferin A is a potent novel inhibitor of HSP90 in human HNSCCs. In addition to HSP modulation, its anticancer mechanistic effects involve apoptotic cell death through the mitochondrial pathway. This molecule shows promise for further in vivo studies to establish preclinical proof of concept as a novel anticancer therapy in this disease. No significant financial relationships to disclose.
Survival for nasopharyngeal cancer with distant metastatic disease at presentation
Authors: Dandona M. A. , Morgensztern D. , Auethavekiat V. , Adkins D. , Thorstad W. , Nussenbaum B. , Zhang Q. , Kuperman D. I. 
Published: August 2020

e17004 Background: Nasopharyngeal carcinoma (NPC) is a unique form of head and neck cancer, with distinct epidemiology and sensitivity to chemotherapy (CT) and radiation (RT). Long-term survival has been reported for selected patients with metastatic disease. However, given its rarity in the Western Hemisphere, data is limited to case series. We used the Surveillance Epidemiology and End Results (SEER) database to determine factors that correlated with prolonged survival in patients with metastatic NPC at presentation. Methods: The SEER database was searched for patients with NPC who have distant metastatic disease at presentation, defined as extent of disease (EOD10) code 85, aged 20 or older, diagnosed between 1988 and 2003. Survival probability was estimated by Kaplan-Meier method and covariate effects were examined using log-rank tests. Parameters evaluated include age, gender, race, tumor grade, and use of RT. Results: Among the 2,610 patients with NPC in SEER, 177 (6.7%) were identified with distant metastatic disease at presentation. Five patients were excluded from subsequent analysis because RT data was not available. RT was administered to 114 patients (66.3%). Median survival was 9 months (95%CI: 7–13 months) and 5-year overall survival (OS) of 20% (95%CI: 14–26%). Outcomes were significantly improved for patients treated with RT compared to those not receiving it, with the 5-year OS rates of 28% versus 3% (p < 0.0001) respectively. Other factors associated with improved survival included non-white race (p = 0.01) and younger age (p < 0.0001). Conclusions: Although SEER lacks information on performance status, site of metastases, and CT use, our data shows that selected patients with metastatic NPC may achieve prolonged survival, particularly if RT is used. It is unclear whether RT is a determinant of better OS or an epiphenomenon. No significant financial relationships to disclose.
A phase II study of single agent OSI-7904L in patients with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN)
Authors: Hough B. , Posner M. , Chung C. , Hainsworth J. , Horan J. , Chick J. , Gibson M. K. 
Published: August 2020

e17005 Background: Given the limited efficacy and relative toxicity of chemotherapy for metastatic or recurrent squamous cell carcinoma of the head and neck, further research is needed to both increase the efficacy and decrease the toxicity of treatment. OSI-7904L is a novel liposomal formulation of a non-competitive thymidylate synthase inhibitor. In a phase I study, 12 mg/m2 dosing given every 21 days was both feasible and well tolerated. Methods: This multi-center, two-stage, phase II trial was designed to assess the efficacy and toxicity of OSI-7904L in patients with advanced, refractory SCCHN. A total of 41 patients were to be enrolled by completion of stage II. Enrollment was limited to patients with histologically proven squamous histology, locally recurrent and/or metastatic disease, with no more than one prior chemotherapy regimen. Patients were required to have a performance status of ≤ 2, predicted life expectancy of at least three months and adequate hematopoietic, hepatic and renal function. Efficacy was assessed according to RECIST guidelines, and toxicity was evaluated per CTC AE 3.0. Results: Ten patients enrolled in stage 1. Median age was 60 (range 42–66). Nine were evaluable for response assessment with one withdrawn after one cycle due to a grade 4 papular rash. There were no objective responses while 4 of the 10 patients had stable disease during their first restaging. Median time to progression was 2.5 months for the 9 evaluable patients. Besides the one grade 4 dermatologic reaction, other toxicities were grade 3 fatigue and dehydration, and grade 2 anorexia. Assuming an expected 20% response rate required to initiate enrollment in stage II, the probability of the tenth patient being a responder was less than 3%, thus the study was closed due to lack of response in this population. Conclusions: OSI-7904L was well tolerated similar to the phase I data, but did not demonstrate efficacy in metastatic or recurrent HNSCC patients. Further study of this drug as a single-agent with the current dosing regimen is not recommended. [Table: see text]
Effect of human papillomavirus (HPV) 16 E6 and E7 gene silencing on epidermal growth factor receptor (EGFR) phosphorylation status in HPV16+oropharyngeal cancer cell lines
Authors: Rampias T. , Sasaki C. , Psyrri A. 
Published: August 2020

e17006 Background: Aberrant activation of EGFR intrinsic tyrosine phosphotransferase activity correlates with poor prognosis in several cancers. In this study, we sought to determine the effect of HPV16 E6 and E7 gene silencing on the status of EGFR phosphorylation in HPV16+ oropharyngeal cancer cell lines. Methods: Short hairpin RNAs targeting HPV type 16 E6 and E7 genes were delivered by retrovirus infection to HPV16+ oropharyngeal cancer cell lines 147T and 090. E6/E7 repression was assessed by quantitative reverse transcription polymerase chain reaction and western blotting for p53 and Rb protein levels 48 hours after retrovirus infection. Phospho-EGFR (Tyr1068), (Tyr845), (Tyr992), (Tyr1045) and total EGFR protein levels before and after silencing were then analyzed by western blotting in 147T and 090 oropharyngeal cancer cell lines. Results: Quantitative RT-PCR analysis showed reduction in E6/E7 mRNA levels up to 85% the level in uninfected or control shRNA infected cell lines. Protein expression revealed substantial downregulation of phospho-EGFR (Tyr992) protein levels, 48 h after the retrovirus infection of 090 and 147T cell lines. A slight reduction of phospho-EGFR (Tyr845) was also observed in both HPV16+ cell lines after silencing. No phosphorylation was detected at sites Y1068 and Y1045 of EGFR. Conclusions: We provide evidence that E6 and E7 are involved in tyrosine phosphorylation of epidermal growth factor receptor at sites Y992 and Y845. Phospho-tyrosine 992 is a direct binding site for the PLCγ SH2 domain and phosphorylation in this site is associated with activation of PLCγ-mediated downstream signaling. Phosphorylation of Tyr845 in the kinase domain is implicated in stabilizing the activation loop maintaining the enzyme in an active state. Since enhanced EGFR activation appears to be a direct consequence of E6/E7 expression, targeting E6/E7 may be effective EGFR blockade in HPV16+oropharyngeal cancers. No significant financial relationships to disclose.