bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation of isotope count with sentinel node positivity in vulvar cancer.
Authors: Woelber Linn Lena , Joosse Simon , Grimm Donata , Mahner Sven , Burandt Eike , Schmalfeldt Barbara , Klutmann Susanne , Prieske Katharina 
Published: September 2018

e17033 Background: Sentinel node biopsy (SNB) has become standard of care in early stage vulvar cancer. As the correlation of isotope count with the presence of metastases remains unclear, often several active nodes are excised per groin. This can result in increased morbidity in node-negative disease despite of SNB. In the current analysis we assess, whether resection of the hottest node could be sufficient to detect sentinel lymph node (SNL) metastasis. Methods: All patients with primary vulvar cancer receiving a SNB with radioactive tracer at the University Medical Center Hamburg-Eppendorf between 2008 and 2015 were evaluated. The day before surgery, patients received four peritumoral intradermal deposits at 3, 6, 9 and 12 o’clock with an overall mean dosage of 85±12MBq99mTc–nanocolloid. Planar lymphscintigraphy was performed one hour after injection. Intraoperatively, a handheld gamma counter was used to identify the SNL. Results: 146 patients with SNB were included; thereof 145 pts underwent bilateral SNB, resulting in 291 analyzed groins. A median of 2 (range 1-7) SNL per groin were removed. From 95/291 (32.6%) groins more than 2 SNL were excised. Median overall SNL isotope count was 1400. In 52 groins, a positive SNL was detected (unilateral in 38 patients, bilateral in 7). The median number of positive SNL per groin was 1 (range 1-4). There was no difference of median count in negative compared to positive SNL (median count 1396 vs. 1614; p=0.90). The SNL with the highest isotope count carried metastases in 36/48 groins (75.0%; in 4 cases the highest count was unknown). In 12/48 (25.0%) positive groins, the SNL with the highest count was not the metastatic SNL (11/12 second highest count). Median count of these 12 SNL was 58.8% of the highest count with a range from 6.0% to 74.0%. Conclusions: The highest isotope count does not reliably detect the positive SNL in vulvar cancer. To prevent mostly fatal groin recurrences, surgeons should continue to remove all SNL accumulating relevant radioactive tracer over minimal background activity.
A comparison of measured and estimated glomerular filtration rate (GFR) for carboplatin dose calculation in women with ovarian cancer (OC).
Authors: Ocen Joanita , Frazer Ricky Dylan , Wright Sarah , Lewis Paul D , Bertelli Gianfilippo 
Published: September 2018

e17051 Background:Carboplatin based chemotherapy is widely used to treat women with Ovarian cancer (OC) in the adjuvant, neoadjuvant and palliative settings. Carboplatin is normally dosed by the Calvert formula: [GRF+25] x AUC, with a target AUC (area under the plasma concentration curve) of 5-6 mg/ml/min. GFR (glomerular filtration rate) can be precisely measured with radionuclide based ligands such as 51Cr-ethylenediamine tetraacetic acid (51Cr-EDTA), but in clinical practice is often estimated using formulae incorporating serum creatinine, weight and age, such as the Cockcroft–Gault (CG) or Wright (WR) formulae. It is unknown, however, if these formulae allow a sufficiently accurate dosing of carboplatin in OC patients. Methods:We retrospectively compared measured (EDTA-based) and estimated (CG and WR formulae) GFR and the resulting carboplatin doses, in women with stage 1c to IV OC treated with carboplatin AUC 6 at our centre between 2015 and 2016. All patients (pts) had concurrent 51Cr-EDTA GFR and serum creatinine measurement before starting carboplatin. Accuracy and bias of The WR and CG formulae were analysed using mean absolute percentage error (MAPE) and mean percentage error (MPE). Results:92 pts were included in the study (median age = 69 years (r. 25 -89), median serum creatinine 63.5 umol/L (r. 38 – 168)). MPE was -37.3 and -26.0 and MAPE was 38.0 and 32.2 for the WR and CG formulae, respectively. If the WR or CG formulae had been used instead of EDTA to calculate the dose of carboplatin, the discrepancy would have been at least 10% in 77.1% and 69.8% of pts, respectively; a discrepancy of 50% or more would have occurred in 10% and 13% of pts. Conclusions:Neither the WR nor CG formulae precisely predict renal function in ovarian cancer pts. They often overestimate GFR, meaning that if these formulae are used instead of isotope-based measurement of GFR, most pts will receive a higher dose of carboplatin. Our findings are relevant for clinical practice and for the design and interpretation of clinical trials, where the choice between EDTA- or formulae- based calculations of carboplatin dose are often left to investigators’ preference.
Phase I study combining olaparib and tremelimumab for the treatment of women with BRCA-deficient recurrent ovarian cancer.
Authors: Adams Sarah Foster , Rixe Olivier , Lee Ji-Hyun , McCance Dennis J. , Westgate Sheri , Eberhardt Steven C. , Rutledge Teresa , Muller Carolyn 
Published: September 2018

e17052 Background: With evidence that BRCA dysfunction is associated with increased T cell recruitment to tumor sites, and that PARP-inhibition may increase the immunogenicity of tumor cells, we evaluated the combination of a PARP-inhibitor and CTLA4 immune checkpoint antibody in BRCA1- ovarian cancer models. Our results demonstrated significant therapeutic synergy and durable treatment responses in preclinical studies. Based on this, a Phase I study was conducted to assess the tolerability of this regimen in women with BRCA mutation-associated recurrent ovarian cancer. Methods: Eligibility criteria included a documented BRCA1 or BRCA2 germline mutations and a diagnosis of recurrent ovarian, tubal, or primary peritoneal cancer with measurable disease. Both platinum-sensitive and platinum resistant patients were eligible. Patients with prior exposure to PARP-inhibitors or to immune therapy with the exception of CTLA4 antibodies were also eligible. Exclusion criteria included current use of anti-inflammatory agents or a prior history of autoimmune disease. Treatment consisted of Olaparib at 300mg twice daily, as well as monthly infusions of Tremelimumab at a dose of 10mg/kg, with plans for a dose reduction if toxicity was encountered. Patients completing two full treatment cycles were evaluated for evidence of toxicity, particularly immune-related adverse events, to define a dose for Phase II testing. Results: Three women were treated at the starting dose of 300mg BID of Olaparib and 10mg/kg monthly of Tremelimumab for two cycles without evidence of any dose-limiting toxicities or grade 3 adverse events. All patients experienced grade 1 and 2 toxicities, including immune related toxicities consistent with prior studies of immune checkpoint inhibitors. All three patients showed evidence of treatment response by cycle 3 based on CA125 levels and a decrease in tumor size on CT scans. Conclusions: The combination of PARP-inhibition and CTLA-4 blockade is tolerable in heavily pre-treated women with recurrent BRCA-associated ovarian cancer. Preliminary results also demonstrate evidence of therapeutic effect, supporting ongoing evaluation of this regimen in Phase II trials. Clinical trial information: NCT02571725.
Harnessing IMGN853-mediated cell cytoxicity response by modulating FRα expression in ovarian cancer.
Authors: Kumar Rajesh , Wei Wei , Lauffer Sam , Fulci Giulia , Birrer Michael J. 
Published: September 2018

e17061 Background: Ovarian cancer (OC) is the fifth leading cause of cancer-related death among women in the United States. Standard treatment includes debulking surgery followed by platinum based chemotherapy. While most tumors respond to this treatment, 70% of the tumors recur and develop into a chemo-resistant disease. There is a need for new therapies targeting recurrent chemoresistant OC. To address this need, Mirvetuximab Soravtansine (ImmunoGen, Waltham, MA) has developed an antigen-drug conjugate (ADC) containing DM4, a highly potent maytansinoid derivative that induces the cell cycle arrest, conjugated to an antibody targeting folate receptor alpha (FRα). Mirvetuximab Soravtansine (IMGN853), was tested in Phase I clinical trials on women with recurrent OC and showed low grade toxicity profile and activity in platinum-resistant disease. The goal of this study is to characterize the mechanism(s) leading to IMGN853 resistance in OC and test whether anticancer drugs targeting these mechanisms could be used in combination with IMGN853 for an additive/synergistic therapeutic effect. Methods: In vitro experiments were performed to detect and modulate FRα expression. Results: We show that sensitivity of OC cell lines to IMGN853 correlates with the expression levels of FRα (R = 0.82). Long-term exposure of sensitive cells to sublethal doses of IMGN853 induces drug resistance which correlates with decreased FRα expression. Anti-cancer drugs such as dexamethasone (Dex), which induces glucocorticoid receptors, or epigenetic modulators (Trichostatin A and 5-Azacytidine) induce FRα expression in SKOV3 and OVCAR8 OC cells, suggesting the possibility to use these drugs to maintain sensitivity of OC cells to IMGN853 and increase its therapeutic window. The therapeutic benefits of combining each of these drugs with IMGN853 will be further tested in mice using ovarian cancer patients’ derived xenografts with different FRα expression levels. Conclusions: These findings have clinical implications as they indicate that OC sensitivity to IMGN853 is modulated in part by changes in FRα levels. Resistance to this drug may be overcome by simultaneous treatment with Dex or other anti-cancer drugs such as TSA or AZA.
The potential of gemcitabine, cisplatin, and bevacizumab combination therapy for patients with ovarian clear cell carcinoma.
Authors: Ito Kimihiko , Nakagawa Mio , Tashima Lena , Yagi Taro , Odani Chihiro , Ono Hitomi , Okubo Rieko , Shimoji Kanoko , Goto Mayako , Tsuruta Tomohiko , Hori Kensuke 
Published: September 2018

e17065 Background: Patients with advanced ovarian clear cell carcinoma (OCC) have poor prognosis, and response rate of chemotherapy for relapsed OCC is less than 10%. The effective standard treatment has not been established yet. The synergic effect between gemcitabine and cisplatin in ovarian cancer patients has been reported. And bevacizumab added on chemotherapy has some evidences of progression-free survival improvement at primary, platinum sensitive relapse and platinum resistant relapse situation than chemotherapy only. Therefore, we conducted a retrospective charts review to examine the safety and efficacy of gemcitabine, cisplatin, and bevacizumab combination (GPB) therapy in OCC patients treated in our hospital. Methods: Intravenous gemcitabine (1,000 mg/m2, day 1, 15), cisplatin (40 mg/m2, day 1, 15), and bevacizumab (15 mg/kg, day 1) were administrated every 28 days. This combination therapy was continued until disease progression or appearance of intolerable toxicity. This retrospective study was approved by our institutional ethics board. Results: Eight patients were treated with this GPB therapy in our institution between April 2013 and August 2015. Six patients received this therapy due to presence of relapse, and 2 patients were administered GPB as post-operative adjuvant therapy. Four patients were not treated with bevacizumab due to their medical conditions. The median treatment cycle was 5.5 (range: 1-15). Six patients were evaluable and their responses were partial response (PR) 1, stable disease (SD) 2, and progressive disease (PD) 3. The overall response rate was 13% and the disease control rate was 50%. Four patients needed dose reduction or treatment delay. Grade 3 adverse events observed were anemia (25%), nausea (13%), and elevation of G-GTP (13%). Conclusions: GPB therapy is feasible and moderately effective for patients with OCC. We are currently conducting the prospective multi-institutional phase II trial (UMIN 000023097) and expect that GPB therapy will be used as the standard treatment regimen for OCC, in future.
Early clinical progression in patients with gynecologic malignancies receiving immunomodulatory antibody therapy.
Authors: Zamarin Dmitriy , Martin Madhuri , Zecca Nicholas , Iasonos Alexia , Zhou Qin , Aghajanian Carol , Sabbatini Paul 
Published: September 2018

e17087 Background: The success of immunomodulatory antibodies have led to their increasing investigation in GYN cancers. Many of these patients, however, discontinue the drugs early in treatment due to symptomatic progression, making it challenging to assess clinical benefit and late responses associated with these agents. Here, we describe the clinical characteristics underlying early progression requiring immunotherapy discontinuation in order to better guide patient selection for such trials. Methods: A retrospective analysis was performed on all GYN cancer patients treated with immunomodulatory antibodies at MSKCC between 1/2013 and 6/2016. Patients were defined as early progressors if they had clinical/radiographic disease progression before 12 weeks which required therapy discontinuation. Logistic regression was applied to model the relationship between baseline clinical and radiographic characteristics and early progression. P<0.05 was considered to be statistically significant. Results: A total of 105 patients met the inclusion criteria, with 74 (71%) with ovarian cancer. Therapeutic targets included CTLA-4 (3%), and PD-1/PD-L1 alone and in combination with other targets (97%). Of these, 55 (52%) met the criteria for early progression requiring therapy discontinuation (median therapy duration 7 weeks, range 1.6-12.1). There was an increased risk for early progression in patients with pre-treatment ascites (p=0.005, OR 6.4, 95% CI 1.7-23.7), and with baseline bulky disease, defined by at least one tumor measuring ≥ 5cm, compared to patients with tumors <5cm (p=0.001, OR 4.1, 95% CI 1.7-9.9). Clinical symptoms/deterioration were the reason for early discontinuation in 35 (64%) of the patients, with symptomatic ascites and abdominal pain as the most common complaints. Conclusions: Symptomatic clinical progression of peritoneal disease leading to early discontinuation of immunomodulatory antibody therapy is common in patients with GYN cancers and is associated with increased pre-treatment disease volume. The extent of peritoneal disease should be taken into strong consideration when selecting GYN cancer patients for trials with immunomodulatory antibody therapy.
Alterations in the uterine microbiome in patients with early endometrial cancer: Variations by ethnicity and obesity.
Authors: Clark Leslie Horn , Keku Temitope O , McCoy Nicole Amber , Hawkins Gabrielle , Bae-Jump Victoria Lin , Brewster Wendy R. 
Published: September 2018

e17114 Background: Obesity and race are known to negatively impact clinical outcomes in endometrial cancer (EC). Mounting evidence suggests the gut microbiome may play an important role in the pathogenesis of both obesity and cancer, however, little is known about the microbiome of the malignant uterus. Further, there is known to be microbiome variability by ethnicity in the vagina and gut. Thus, we sought to evaluate the microbiota of ECs and to assess for variations by obesity and race. Methods: Following IRB approval, banked tumor specimens of patients undergoing hysterectomy for management of endometrioid EC were identified. Tumors were analyzed from African-American (AA) and Caucasian (CAU) patients and stratified as obese (BMI ≥ 30kg/m2) or non-obese (BMI < 30kg/m2). The microbiota of the endometrial tumors were characterized by 16S rRNA high throughput sequencing. Descriptive statistics were performed. Results: We evaluated specimens from 11 AA (52%) and 10 CAU (48%). The median age was 68.9 years. Majority of women were postmenopausal (n=17, 81%) and obese (n=14, 66.7%). Tumor grade was evenly distributed with 7 grade 1 (33.3%), 6 grade 2 (28.6%), and 8 grade 3 tumors (38.1%). We found that EC microbiota richness was higher in AA than CAU (p=0.02). When analyzed by race and obesity status, we observed significant differences in EC microbiota composition. The microbiota composition differed between obese AA and obese CAU (p=0.04). In obese subjects the distribution of Proteobacteria was 55% AA vs. 30.7% CAU (p=0.02) while Actinobacteria abundance was 17.8% versus 34.4% (p=0.05) (Table 1). Among CAU, the EC microbiota profile differed between obese and non-obese (p=0.07). At the genus level, the relative abundances of Delftia, Finelgoldia, Geobacillus, Propionibacterium and Pseudomonasvaried by obesity and race. Conclusions: Bacteria exist in the malignant uterus. EC microbiota diversity was greater in tumors of AA versus CAU women, and tumor microbiota profiles were distinct between ECs of obese and lean women. Better understanding of the inter-relationship of obesity and race on the EC microbiota may provide critical insight into the disparate clinical outcomes between AA and CAU women with EC.
TWISTT analysis of open labeled multicentric study of BIOMAb- EGFR [Nimotuzumab] in head and neck cancers with chemotherapy and/or radiotherapy.
Authors: Pawar Dilip , Attili Suresh VS , Sunkavalli Chinnababu 
Published: September 2018

e17505 Background: Head and neck Squamous Cell Cancer (HNSCC) have poor prognosis in recurrent and metastatic setting with limited treatment options. The treatment decision are predominantly driven by quality of life (QOL) issues, pharmaco-economics besides the survival and response rates. Present TWISTT analysis was based on the earlier “open labeled multicentric study of Nimotuzumab in head and neck cancers with chemotherapy and/or radiotherapy”, to evaluate the QOL outcomes Methods: The active part study was conducted between Nov 2007 and Jan 2009 followed by long term follow up. Patients received Nimotuzumab w at 200 mg/m2 / week along with RT or chemotherapy Results: A total of 150 patients received therapy, who met the eligibility criteria [ Ref-CTRI/2007/95] Overall adverse event rate is 24% [ 36 subjects who experienced any AE]. Mucosal inflammation [ related to RT] was most frequent AE and three were only 4 [2.7%] serious adverse events [ all of them not related to IP]. Skin rash was not apredictor for the response to BIOMAB and was observed in 1.3%. The median TWISTT score in responding patients was 246 days vs 128 days for non responders. PFS and OS were not presented as the main focus of the study is to report the QOL and TWISTT score. Conclusions: Based on the results of this analysis, Nimotuzumab in combination with chemo +/- radiotherapy appears as an attractive regimen for patients with metastatic HNSCC. Clinical trial information: CTRI/2007/95.
Small cell carcinoma of the head and neck: Incidence and survival trends based on the Surveillance and Epidemiologic and End Results (SEER) analysis.
Authors: Bean Marta , Goodman Michael , Steuer Conor Ernst , Patel Mihir , McDonald Mark William , Higgins Kristin Ann , Owonikoko Taofeek Kunle , Beitler Jonathan Jay , Shin Dong Moon , Saba Nabil F. 
Published: September 2018

e17508 Background: Small cell carcinomas of the head and neck (SmCCHN) are rare neoplasms with an unfavorable prognosis. Population based data describing survival and prognostic factors for this malignancy are limited. Methods: Data was obtained from the US National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) database for the period 1973-2013. Patient and tumor related characteristics for SmCCHN were compared with squamous cell carcinomas (SCC) of the same anatomic sites. Survival for the two groups was compared by constructing Kaplan-Meier curves and Cox proportional hazard models with and without propensity score matching. Cox models results were expressed as hazard ratios (HR) and the corresponding 95% confidence interval (CI). Results: The dataset included 609 SmCCHN and 227943 cases of SCCHN. SCCHN patients with SmCCHN included significantly greater proportions of females and whites. SmCCHN was more likely to originate in the salivary glands and present with more advanced stage and grade. The overall 5 year and 10 year survival estimates were 27% and 18%, respectively. Corresponding values for SCCHN were 46% and 31%. The multivariable analyses adjusting for age, sex, race, marital status, year of diagnosis, stage, grade and receipt of radiation, the HR comparing SmCCHN to SCCHN was 1.53 (95% CI: 1.39-1.68). Elderly, male, black and not married persons had worse prognosis compared to their respective reference groups. Other factors independently associated with lower survival included more advanced stage and tumor grade, and earlier decades of diagnosis. In the propensity score matched analyses the corresponding HR was 1.27 (95% CI: 1.15-1.40). Conclusions: Compared to SCCHN, SmCCHN in addition to carrying a worse survival, is more likely to originate in the salivary glands, present with more advanced stage, and affect females and whites.
Survival and side effects from novel alternative regimen for squamous cell head and neck cancer.
Authors: Bishnoi Rohit , Bejjanki Harini , Bennett Jeffery A , Reisman David , Shah Chintan 
Published: September 2018

e17515 Background: Toxicity of the standard regimens is a major limitation in treatment of head/neck cancer which impacted about 61,000 persons in 2016 in USA of which 13,000 died. We present data herein with low dose chemotherapy (metronomic) using commonly used drugs Taxols, Platins, 5-Flurouracil and EGFR inhibitors. We achieved equal or better outcomes as compared to standard dosing with minimal side effects (level 3/4). Methods: This is a retrospective study on squamous cell head and neck cancer patients where standard first line therapies were started at ½ normal dosing and was increased until the emergence of side effects and titrated thereafter. Results: Patient population consisted of 32 patients with 87% males and with median age 65.2 years where 59% had recurrent disease, 71% locally advanced and 28% had metastatic disease. Total 270 chemotherapy cycles were delivered among these 32 patients with median of 9 cycles. Median dose for Cispatin was 45mg/m2, Paclitaxol was 80mg/m2, 5-FU was 360mg/m2/day. Cetuximab was used at standard doses. 6 patients who achieved long-term disease control were then placed on immunotherapy with either Nivolumab (median dose of 3mg/kg) or Pembrolizumab (median dose of 2mg/kg) and got median of 7 cyles. Out of 32, 9 patients (28%) achieved complete remission, 3 patients (9%) achieved near-complete remission with more than 95% reduction in tumor size. Overall disease control rate was 68% and overall response rate was 59%. Out of 9 patients who achieved complete remission 5 underwent surgical exploration and 1 went for cryo-ablation and no residual tumor was found. Measuring tumor volume in patients who achieved disease control showed volume reduction of 53%, 62% and 78% in 1st, 2nd and 3rdfollow up surveillance studies at mean interval of 101 , 186 and 331 days showing steady response. Median Progression free survival was 17.8 months and overall survival at 40 months was 54%. Notable high-grade toxicities were generalized fatigue in 12.5% (n = 4), grade 3 neutropenia in 18% (n = 6) and grade 4 neutropenia in 1 patient. Conclusions: These excellent results, low toxicity and subsequent good quality of life encourage patient tailored approach rather than one-size fits all approach.