bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of dose-dense chemotherapy as first-line treatment of advanced ovarian cancer patients after non-optimal debulking.
Authors: Rumyantsev Alexey , Tyulyandina Alexandra , Pokataev Ilya , Morkhov Konstantin , Nechuskina Valentina Mikhailovna , Tjulandin Sergei
Published: May 2020

e18066

Background: Patients with advanced ovarian cancer have unfavorable prognosis after primary debulking surgery if the size of residual tumor exceeds 1 cm. The optimal approaches to systemic treatment of these patients remain unknown. We evaluated the efficacy and safety of dose-dose chemotherapy in frontline treatment of ovarian cancer patients after upfront non-optimal debulking surgery. Methods: This was a non-randomized single-arm phase II trial. We enrolled patients with advanced (FIGO III-IV) epithelial ovarian who underwent non-optimal upfront debulking surgery with residual tumor size > 10 mm. All patients were treated with dose-dense chemotherapy (ie, paclitaxel 80 mg/m2 day 1, 8, 15 + carboplatin AUC6 day 1, cycled every 21 days – 6 cycles). Patients in historical control arm received standard chemotherapy with paclitaxel 175 mg/m2 day 1 + carboplatin AUC6 day 1, cycled every 21 days – 6 cycles. No patient in experimental or control arm received front-line bevacizumab or PARP inhibitors. The primary endpoint of the trial was progression-free survival (PFS). According to the historical data of our department, 1-year PFS in this category of patients equals to 51%. To increase 1-year PFS to 70%, 40 patients should be enrolled with α = 0.05 and β = 0.20 and estimated data loss for 10% of patients. Results: The study enrolled 40 patients to dose-dense chemotherapy arm, control arm included 86 patients. The trial arms were balanced in terms of age, performance status and other characteristics. Median follow-up was 28.8 months. The 1-year PFS was 76.9% compared to 51% in historical arm, median PFS was 19.8 months and 12 months respectively (HR 0.61; 95% CI 0.39-0.95; p = 0,03). The 1-year overall survival rate was 92.3% with median OS not reached with specified follow-up period. Severe neutropenia, anemia, thrombocytopenia was observed in 82.1%, 53.8%, 15.3% of patients, respectively. Conclusions: The results of the study showed high efficacy of dose-dose chemotherapy as front line of treatment for advanced ovarian cancer patients after non-optimal upfront debulking surgery but one should consider high toxicity of this regimen.
Anlotinib (AL3818) plus pemetrexed in patients with recurrent platinum-resistant advanced epithelial ovarian cancer: A single-arm, open-label, phase II study.
Authors: Zhang Yanna , Chen Jueming , Wei Wei , Zheng Lie , Li Han , Feng Yanling , Wan Ting , Qiu Jiaqi , Jiang Xingyu , Xiong Ying , Li Jundong , Song Libing , Liu Jihong , Huang He
Published: May 2020

e18078

Background: Anlotinib (AL3818) is a novel multi-target tyrosine kinase inhibitor that has previously shown clinical antitumor activity in various cancers, including the phase I study on tumors of female reproductive system. This phase II study (ChiCTR1800018192) aims to further evaluate the safety and efficacy of anlotinib combined with pemetrexed in patients with recurrent platinum-resistant advanced epithelial ovarian cancer. Methods: Patients who underwent cytoreductive operation, with histopathologically advanced epithelial ovarian cancer ( FIGO staging III or IV), and failed to previously platinum-based chemotherapies were considered eligible for enrollment to receive combined treatment of anlotinib (12 mg per day, days 1-14; 21 days per cycle) plus pemetrexed (0.5 g/m2, day 1; 21 days per cycle). Total duration of combined treatment contained 6 cycles, and subsequent maintenance treatment was anlotinib monotherapy (12 mg per day, days 1-14; 21 days per cycle) till disease progression or intolerant toxicity. The primary endpoint of this study was objective response rate (ORR) and the secondary endpoints were disease control rate (DCR), progression-free survival (PFS) and safety. Results: Between 2018 July and 2019 October, 13 patients (female) with a median age of 55 years (range: 41 - 65), FIGO histopathological stage IIIA (7.7%) or IIIC (76.9%) or IV (15.4%) were enrolled. Over a mean follow-up period of 5.9 (95% CI: 3.4-8.3) months, therapeutic evaluation showed the incidence of partial response, stable disease, and progression disease was 38.5%, 53.8% and 7.7% respectively, yielding the ORR of 38.5% (5/13; 95% CI: 13.9%-68.4%) and the DCR of 92.3% (12/13; 95% CI: 64.0%-99.8%). The median PFS was not reached. Frequently occurring adverse events (AEs) were grade 1 or 2, including hand-foot syndrome (53.8%), allergic eruption (38.5%), mild hypertention (30.8%), fatigue (23.1%), diarrhea (23.1%), gum-pain (15.4%), and dry cough (15.4%). High grade AE was only observed in 1 patients with hemoglobin reduction of grade 4. Neither unexpected safety signals nor treatment related death occurred. Conclusions: Anlotinib (AL3818) plus pemetrexed showed a promising activity with an acceptable safety profile for previously platinum-treated patients with recurrent advanced epithelial ovarian cancer. Clinical trial information: ChiCTR1800018192.
Multiomics-based energy metabolism heterogeneity and its regulation by antiparasite drug ivermectin.
Authors: Li Na , Zhan Xianquan
Published: May 2020

e18080

Background: Energy metabolism heterogeneity is a hallmark in ovarian cancer, namely the Warburg effect and the reverse Warburg effects coexist in ovarian cancer. Exploration of energy metabolism heterogeneity benefits for discovery of the effective biomarkers for ovarian cancers. Methods: Comprehensive analysis of mitochondrial proteomics data (1198 mitochondrial differentially expressed proteins), mitochondrial phosphorpoteomics data (67 mitochondrial phosphorproteins), proteomics data (205 differentially expressed proteins), and transcriptomics data (20115 genes in 419 ovarian cancer samples) was useful. Results: It revealed (i) the upregulations of rate-limiting enzymes PKM2 in glycolysis, IDH2 in Kreb’s cycle, and UQCRH in oxidative phosphorylation (OXPHOS) pathways, (ii) the upregulation of PDHB that converts pyruvate from glycolysis into acetyl-CoA in Kreb’s cycle. Anti-parasite drug ivermectin demonstrated its strong abilities to inhibit proliferation and cell cycle progression and promote apoptosis in EOC cells, through molecular networks to target PFKP in glycolysis, IDH2 and IDH3B in Kreb’s cycle, ND2, ND5, CYTB, and UQCRH in OXPHOS, and MCT1 and MCT4 in lactate shuttle to inhibit EOC growth. Those results were further confirmed in the ovarian cancer cell models and tissues. Conclusions: It clearly concluded that ivermectin might have new potential for ovarian cancer treatment through regulating energy metabolism pathways. These findings provide more accurate understanding of molecular mechanisms of ovarian cancers and discovery of effective energy-metabolism-heterogeneity-based therapeutic drugs for ovarian cancers.
Pressurized intra peritoneal aerosol chemotherapy (PIPAC) vs. intravenous chemotherapy to assess quality of life & response rates in unresectable peritoneal metastases secondary to platinum resistant ovarian cancer: A comparative study.
Authors: Somashekhar S.P. , C. Rohit Kumar , Rajgopal Ashwin K. , Rauthan Amit , Patil Poonam , Kapoor Priya
Published: May 2020

e18091

Background: The primary objective of this study is to assess Qol & response rates in platinum resistant ovarian cancer patients with peritoneal metastasis treated with PIPAC procedure in comparison with conventional systemic intravenous chemotherapy. Methods: Between October 2017 and December 2019, 31 PIPAC applications were done in 15 patients with cisplatin 10.5mg/m2 and doxorubicin 2.1mg/m2. During same period 20 patients received systemic chemotherapy with clinician’s choice of drug ((mono-therapy consisting of pegylated liposomal doxorubicin or topotecan or gemcitabine or paclitaxel weekly with or without bevacizumab).The response rate (With MRI & Ca-125) & quality of life assessment (QLQ C-30) of both the group was done periodically and recorded. Results: Overall 35 patients were analysed in this study. The results have been presented in Table. Conclusions: PIPAC in comparison to intravenous chemotherapy for platinum resistant ovarian cancer with peritoneal metastasis showed better response rates (66.6 vs. 22.4%) and improved quality of life score. PIPAC has shown promising results and should be in the arsenal of the clinicians managing patients with platinum resistant ovarian cancer. [Table: see text]
Efficacy and toxicity of immunotherapy with immune checkpoint inhibitors in gynecologic cancers.
Authors: Kuznicki Michelle , Joehlin-Price Amy , Rose Peter Graham , Mahdi Haider
Published: May 2020

e18092

Background: There is limited data on outcomes for gynecologic cancer patients treated with immune checkpoint inhibitors (ICI) outside the scope of clinical trials. Here we present our Institutional experience with a cohort of endometrial (EC) and ovarian cancer (OC) treated with ICI. Methods: 59 patients who received ICI were included (23 OC and 36 EC). Progression-free (PFS) and Overall survivals (OS) were determined by Kaplan-Meier (KM) curve and log rank test. Comparison of duration of response (DOR) and stable disease (DOSD) was done with unpaired t-test or one-way ANOVA. Rates of objective response (ORR) including partial response (PR) and complete response (CR), and stable disease (SD) were compared by Fischer’s exact test. Results: Median age was 66 years. 23 patients were microsatellite stable (MSS), 23 microsatellite instability high (MSI-H). Median number of prior lines was 2 (0-11). PFS and OS for EC and OC were overlapping; therefore outcomes for both were combined [(PFS 6.4m OC vs 7.3 m EC, p = 0.61), (OS 15.9 m OC vs 14.2 m EC, p = 0.78)]. Response rates consisted of 20.3% PR, 8.5% CR, 37.3% SD. Differences in responses were noted for clear cell carcinoma (CC) (33.3% PR, 11.1% CR, 33.3% SD) and MSI-H (36.4% PR, 18.2% CR, 22.7% SD) compared to MSS (11.8% PR, 0% CR, 47% SD). MSI-H had higher ORR vs. MSS (54.1% vs 11.8%, p = 0.0078). CC trended toward improved ORR vs. MSS (44.4% vs 11.8%, p = 0.14). PFS was improved for MSI-H vs. MSS (10m v 5.0m, p = 0.03). OS for CC compared to any other histology was improved (NR vs 12.8m respectively, p = 0.009). 5 recurrent MSI-H EC patients received ICI as first line monotherapy. Responses included 4 PR and 1 SD (80% ORR, 100% clinical benefit). PFS was 9.2m (3.3-13.3). 80% remained progression-free at last follow up. Overall, 38.9% experienced toxicity: hypothyroidism (15%), dermatitis (5%), pneumonitis (10%), LFT elevation (2%), amylase/lipase elevation (3%), colitis or diarrhea (5%), uveitis (2%) or nephritis (5%). 10% of patients required discontinuation of ICI secondary to toxicity. Trends for PFS and OS favored improved outcomes in patients with toxicity vs. no toxicity [(PFS 12.9m vs 5.6m, p = 0.07), (OS 22.9m vs 13.1m, p = NS)] respectively. Conclusions: In this study, immunotherapy with ICI outcomes favor MSI-H and CC compared to MSS disease. CC had promising OS compared to other histology types. ICI showed promising efficacy in MSI-H EC with 100% clinical benefit rate in chemonaive patients. First line ICI should be investigated in these patients. Positive correlation between toxicity and outcome is noted and will be further investigated.
Impact of neoadjuvant chemotherapy on survival in women with endometrial cancer: A National Cancer Database analysis.
Authors: Chambers Laura , Jia Xuefei , Alhilli Mariam
Published: May 2020

e18094

Background: To evaluate overall survival (OS), prognostic factors for survival, and treatment outcomes in patients with Stage III/IV endometrial cancer (EC) undergoing neoadjuvant chemotherapy +/- surgery compared to surgery followed by adjuvant chemotherapy. Methods: The National Cancer Database (NCDB) was queried to identify patients with Stage III/IV EC who were treated with chemotherapy. Univariable and multivariable Cox proportional hazards analyses were used to determine independent prognostic factors for OS. Survival was measured from date of diagnosis to the date of last contact or death. Results: From 2004-2012, 31,726 women with stage III/IV EC were identified. . Treatment groups consisted of: 3424 (10.8%) chemotherapy alone (C), 26926 (84.9%) surgery followed by chemotherapy (S+C), and 1412 (4.4%) neoadjuvant chemotherapy followed by surgery (NACT+S). The median age at diagnosis was 64 years (19-90), and 65.8% (n = 35402) of patients had Stage III disease. Reasons for no surgery were: not part of primary treatment plan (77.7%; n = 5859), contraindicated due to patient factors (11.3%, n = 850) or patient refusal (3.6%; n = 268). The majority of patients (86.8%) received multiple chemotherapy agents and 1988 (6.3%) received single agent chemotherapy. Charlson-Deyo score was 0 for 75.3% (n = 2578) of C, 76.7% (n = 20652) of S+C and 77.8% (n = 1098) of NACT+S patients (p < 0.001). Compared to patients who received C alone, S+C and NACT+S were associated with improved median OS (10.9 months vs. 63.3 (HR 0.27 CI 0.26-0.28, p < 0.001) and 24.6 months (HR 0.50, 95% CI 0.47-0.54, p < 0.001), respectively). On multivariate analysis advanced age (HR 1.03, p < 0.001), stage IV disease (HR 2.70, p < 0.001), Charlson Deyo Score (1 – HR 1.13, p < 0.001; 2 – HR 1.32, p < 0.001), and African American race (HR 1.53, p < 0.001) were associated with worse OS.Private insurance (HR 0.87, p < 0.001), income > $63,000 (HR 0.86, p < 0.001) and treatment with S+C (HR = 0.32, p < 0.001) or NACT+S (HR 0.44, p < 0.001) versus C alone were predictive of improved OS. Conclusions: In this analysis of the NCDB, receipt of chemotherapy alone is associated with markedly worse OS than S+C or NACT +S in stage III/IV patients. . Socioeconomic factors including African American race, insurance status and income are independent predictors for survival in this cohort. Where feasible, surgery should be should be incorporated into treatment planning for women with Stage III/IV EC.
Chemotherapy response score as a prognostic tool in advanced-stage endometrial cancer patients treated with neoadjuvant chemotherapy.
Authors: Jani Ina , Lastra Ricardo R. , Brito Katherine , Liao Chuanhong , Lazo Isabel , Lee Nita Karnik , Yamada Seiko Diane
Published: May 2020

e18095

Background: Chemotherapy response score (CRS) applied to omental metastases obtained at the time of interval debulking surgery (IDS) has been used to quantify response to neoadjuvant chemotherapy (NACT) in advanced stage ovarian cancer patients. The score has been correlated with both progression free survival (PFS) and overall survival (OS). This CRS score has not been studied in advanced stage endometrial cancer. The aim of the current study is 1) to apply the CRS to omental and adnexal metastases obtained at IDS of advanced stage endometrial cancer patients and 2) to investigate the association between the CRS score and surgical outcome, PFS and OS. Methods: Patients with clinical stage III-IV endometrial cancer (endometrioid, serous, clear cell, carcinosarcoma) were identified through the endometrial cancer database, billing data and tumor board notes (2003-2019) from the University of Chicago. Patients were included if they received NACT followed by IDS (R0 no gross residual, optimal < 1 cm residual or suboptimal ≥ 1 cm residual disease). Patients who received pre-operative radiotherapy were excluded. Pathology specimens from primary and metastatic sites were reviewed by the study pathologist blinded to clinical outcome. Histologic specimens from the omental and adnexal metastases were assigned a single quantitative score of 1 (no/minimal tumor response), 2 (appreciable tumor response with viable tumor) or 3 (complete/near complete response) using the CRS system as previously described by Bohm et al (JCO 2015; 33:2457-63). Results: A total of 40 patients were available for analysis. Median age 63.5, median BMI 32 kg/m2. There is a significant association between omental CRS and optimal IDS (p = 0.029) but no significant association between the adnexal CRS and optimal IDS (p = 0.145). Cox regression analysis identified CRS omentum [2: HR = 0.095, p = 0.001; 3 HR = 0.088, p = 0.004] and CRS adnexa [2: HR = 0.24, p = 0.007] predictive of PFS. There was not enough evidence to comment on any association between CRS with OS. Conclusions: Omental CRS2, CRS3 are associated with optimal IDS. Omental CRS2, CRS3 and adnexal CRS2 are prognostic for improved PFS in stage III – IV endometrial cancer patients after neoadjuvant chemotherapy. [Table: see text]
Seven-year survival analysis in women with unsuspected uterine malignancy after laparotomic versus laparoscopic hysterectomy: A national claim data retrospective cohort study.
Authors: Lee Jung Hun , Yuk Jin-Sung
Published: May 2020

e18096

Background: The primary aim of this study was to compare the overall survival of women with unsuspected uterine malignancy (UUM) diagnosed after laparotomic versus laparoscopic hysterectomy for benign gynecological diseases. Methods: A national health insurance database was analyzed from January 2006 to December 2010 to estimate the incidence and mortality of UUM diagnosed after hysterectomy for benign gynecologic diseases using diagnostic and procedure codes. Results: From the database (24 million women annually), 157,232 women were extracted. These women were divided into a laparotomic group (n = 103,631) and a laparoscopic group (n = 53,601). The overall incidences of UUM, unsuspected endometrial cancer, and UUM other than endometrial cancer were 0.65%, 0.46%, and 0.19%, respectively. Women with UUM diagnosed after hysterectomy showed no difference in mean age, incidence of UUM, or socioeconomic status in either group. Kaplan-Meier survival analysis and Cox regression analysis showed that the laparoscopic group was associated with more favorable overall survival than the laparotomic group, especially in UUM other than endometrial cancer ( p < 0.001). Conclusions: In women with UUM diagnosed after hysterectomy for presumed benign gynecological diseases, overall survival up to 7 years favors laparoscopic hysterectomy over laparotomic hysterectomy, and the incidence of UUM is relatively low. However, considering the devastating effect of intraperitoneal dissemination of UUM, surgeons should fully explain this issue to patients preoperatively and try to avoid intraperitoneal spread of tumor cells intraoperatively. [Table: see text]
A phase I trial of nab-paclitaxel/bevacizumab (AB160) nano-immunoconjugate therapy for metastatic gynecological malignancies: MC1371 (NCT02020707).
Authors: Kalogera Eleftheria , Suman Vera Jean , Nevala Wendy Kay , Finnes Heidi Diann , Schimke Jill , Strand Carrie , Glaser Gretchen , Grudem Megan , Jatoi Aminah , Klampe Carolyn , Kumar Amanika , Langstraat Carrie L , Wahner Hendrickson Andrea Elisabeth , Weroha Saravut John , Reid Joel M. , Markovic Svetomir , Block Matthew Stephen
Published: May 2020

e18097

Background: AB160 is a 160 nm nano-immunoconjugate consisting of nab-paclitaxel (NP) nanoparticles non-covalently coated with bevacizumab (BEV) for targeted delivery into tissues expressing high levels of vascular-endothelial growth factor (VEGF). Both taxanes (GOG-0129C, GOG-0126R, GOG-0127V) and BEV (GOG-0229E, AURELIA, GOG-0227C) have demonstrated clinical activity in previously treated metastatic endometrial cancer (EC), ovarian cancer (OC), and cervical cancer (CC), respectively. Methods: A 3+3 phase I trial was conducted in patients with EC, platinum-resistant OC and CC who had prior systemic treatment for metastatic disease to determine the maximum tolerated dose of AB160 administered intravenously on days 1, 8 and 15 of a 28-day cycle. The starting dose level (DL1) was NP at 125 mg/m2 with BEV at 50 mg/m2. There were 2 higher dose levels: DL2 (NP at 150 mg/m2 with BEV at 60 mg/m2) and DL3 (NP at 175 mg/m2 with BEV at 70 mg/m2). Dose limiting toxicities (DLT) included grade (G) 4 neutropenia or anemia, PLT < 25,000, serum creatinine ≥2 times baseline, G2-4 neurologic toxicity or G3-4 non-hematologic toxicities. Disease evaluations were conducted after every 2 treatment cycles using RECIST criteria. Patients were treated until disease progression or intolerability. Samples were collected for pharmacokinetic (PK) studies. Results: Nine women 41 – 74 years of age (median 57) have enrolled (5 with EC and 4 with OC); data are available for the first 8. No DLTs have been observed among the 3 women enrolled on DL1, 3 women on DL2, and 2 women on DL3. All 3 patients on DL3 continue on treatment. The other 6 patients have discontinued due to adverse reactions (3), progression (2), and patient choice (1). The median number of cycles administered is 6 (4-14). The most common severe (G3/4) toxicities include neutropenia (37.5%) and leukopenia (25%). There have been 5 partial responses (62.5%): 1 on DL1 and 2 each on DL2 and DL3. PK evaluation is pending. Conclusions: AB160 therapy is safe and demonstrates promising clinical activity in patients with previously treated metastatic gynecologic malignancies. Further clinical testing is being pursued in this patient population. Clinical trial information: NCT02020707.
A Novel predictive probability algorithm to determine risk for malignancy between uterine fibroids versus uterine sarcoma.
Authors: Blackman Alexandra Michelle , Samborski Alexandra , Miller Michael Craig , Singh Rakesh , Kim Kyu Kwang , Turner Rachael , Messerlian Geralyn , Moore Richard G.
Published: May 2020

e18098

Background: The combination of HE4 and CA125 can be used as a predictive probability algorithm to determine the risk of malignancy in women with a uterine mass. Many studies have been done looking at ways to differentiate between benign fibroids and uterine sarcomas with limited success. This study examined the utility of using a logistics regression algorithm containing biomarkers HE4 and CA 125 to predict risk of malignancy of a uterine mass. Methods: This was an IRB retrospective study using de-identified data form 5 pelvic mass studies. Patients were included if they were diagnosed with either uterine fibroids or uterine sarcoma on final pathology. Pre-operative serum levels of HE4 and CA125 were obtained for each patient. A logistics regression analysis was performed in a prior pelvic mass prospective trial and utilized in this analysis. The predictive probability algorithm was used to classify patients into high and low risk groups for sarcoma. Wilson’s score interval was used to determine confidence intervals. Results: There were 71 patients identified with a uterine mass. The mean age of study participants was 54 (range 22-85). There were 10 (14.1%) sarcomas and 61 fibroids (85.9%) identified. Six of the sarcomas were leiomyosarcomas (60.0%). There was 1 adenosarcoma (10%), 1 mixed sarcoma (10%) and 2 sarcomas which were not further characterized. A threshold of 13.1% was used to classify masses as low or high risk. The predictive probability algorithm was found to have a sensitivity of 90.9% (CI 55.5-99.7%), specificity of 60.7% (CI 47.3-72.9%), PPV of 27.3% (13.3-45.5%), and NPV of 97.4% (86.2-99.9%). An elevated risk of malignancy was noted in 9 (90%) sarcomas and 24 (39%) of fibroids. Conclusions: A predictive probability algorithm using HE4 and CA 125 had a high sensitivity for determining high and low risk of malignancy in patients with presumed uterine fibroids with a sensitivity of 90.9% for detecting sarcoma. This algorithm will be validated in a prospective clinical trial.
A single-center analysis of adjuvant sequential versus ‘sandwich’ chemoradiotherapy for patients with stage III endometrial cancer.
Authors: Shen Janice , Newman James , Hernandez Jennifer , Bloom Beatrice , Lee Jean Kyung , John Veena S.
Published: May 2020

e18101

Background: To determine if the sequencing of chemotherapy with external beam radiotherapy (EBRT) in the adjuvant setting for FIGO stage III endometrial cancer impacts 2-year progression free survival (PFS). Methods: As part of our Gynecologic Oncology Multidisciplinary Group's initiative to establish an institutional guideline for the adjuvant treatment of Stage III endometrial cancer, we reviewed 144 cases identified by our cancer registry and departmental database. Treatment regimens were divided into three categories: sequential therapy with six cycles of carboplatin/taxane followed by EBRT, concurrent cisplatin for two cycles with EBRT followed by four cycles of carboplatin/taxane, or ‘sandwich’ therapy with three cycles of carboplatin/taxane followed by EBRT followed by three cycles of carboplatin/taxane. The published results of the phase III GOG-258 study called into question the efficacy of concurrent chemoradiation. Therefore, we only compared sequential versus ‘sandwich’ therapy using a Chi-Square analysis. We conducted a retrospective chart review to assess if patients were able to complete the prescribed six cycles and EBRT, and then measured their PFS at two years. We hypothesized that there would be no difference in PFS between the two groups. Results: There were no significant differences in clinical or pathologic factors between patients treated with either regimen. Ninety-four patients (65%) had stage IIIC disease. The majority of patients received six cycles of paclitaxel with carboplatin. Median EBRT dose was 45 Gy. There was no statistically significant difference in the estimated 2-year PFS between the sequential and ‘sandwich’ groups, which were 82% and 82.5%, respectively (p = 0.84). Conclusions: Adjuvant chemoradiation for FIGO stage III endometrial cancer given sequentially or in a ‘sandwich’ fashion appears to offer equally excellent early clinical patient outcomes.
Age-related clinicopathologic features and survival in papillary serous uterine cancer patients older and younger than 70: An exploratory analysis of a series of consecutive patients.
Authors: Lerner Jaren , Michel Miguel , Iskandar Andrew Samir , Kaur Jaspreet , Tuler Shahaf , Farrell Stephanie , Plaxe Steven C. , Dasanu Constantin
Published: May 2020

e18104

Background: Papillary serous uterine cancer (PSUC) is a rare, clinically aggressive histotype accounting for 40% of uterine cancer deaths. Clinicopathologic characteristics and outcomes between older and younger PSUC patients may differ. Methods: With IRB approval, we conducted a retrospective analysis of 554 consecutive patients with uterine cancer treated at our institution from 2009-19. Consistent with findings from the SEER database, 28 patients (5%) had PSUC. Most PSUC patients were Caucasian; Latinas comprised 14.2%. Thirteen patients were seventy years of age or younger (≤70) and fifteen were older than seventy ( > 70). Clinicopathologic features, therapy and survival were compared between two cohorts. Statistical analysis: Significance of associations was assessed with Fishers' exact test. Survival analysis was performed with Cox proportional model with censoring to calculate hazard ratios (HR). Results: The two cohorts were well-balanced for stage (TNM stages I+II vs. TNM stages III+IV). More than 90% of patients in each group had surgical excision/debulking, and nearly half of patients in each group received systemic chemotherapy. The most frequently used chemotherapy regimen was carboplatin-paclitaxel. Compared to patients ≤70, patients > 70 were less likely to undergo postoperative radiation therapy (6% vs 61.5%; p = 0.001). Cancer-specific survival (CSS) was worse in patients > 70 as opposed to patients ≤70 (21.8 vs. 27.4 months; HR 0.61, p = 0.03). Four PSUC patients > 70 had a personal history of metachronous breast cancer; none ≤70 had a history of breast cancer. We identified five cases of breast cancer, two cases of colon cancer, and one case each of ovarian and uterine cancer in first-degree relatives of PSUC patients > 70. Conclusions: Older PSUC patients displayed significantly shorter CSS than their younger counterparts. They were also less likely to receive radiation therapy. As personal and family history of older PCUS patients identified an excess of other cancers, comprehensive germline mutation testing may be warranted. Final statistical analysis, comparison to SEER data and significance will be presented.
A review of head and neck squamous cell carcinoma response to taxane chemotherapy treatment in the pre versus post nivolumab era.
Authors: moloney carolyn , Sukor Sue , McCarthy Michael Thomas , Grant Cliona
Published: May 2020

e18504

Background: Nivolumab received FDA approval as monotherapy for the treatment of recurrent or metastatic squamous cell carcinoma (SCC) of the head and neck after failure of platinum-based therapy in 2016. This approval was based on CheckMate 141. When patients ultimately relapse after immunotherapy in the second line setting, third line agents include single agent or combination treatment with a Taxane. Methods: We identified patients with metastatic or recurrent squamous cell head and neck cancer in an Irish hospital who had received Taxane chemotherapy after immunotherapy. We looked at outcomes for these patients including progression free survival (PFS) and overall survival (OS). We then identified a group of patients who received a Taxane following platinum failure in the pre-Nivolumab era to act as a comparator. Our objective was to compare PFS and OS to subsequent Taxane chemotherapy in the era before and after the introduction of Nivolumab as a therapy for platinum refractory head and neck SCC. Results: This retrospective cohort study was made up of 26 patients with metastatic or recurrent head and neck cancer. Primary sites included oropharynx, oral cavity, larynx and nasal cavity squamous cell cancers. The patients had a median age of 56. 13 of these patients identified had progressed on Nivolumab but remained fit for a next line of treatment. Median PFS in this group on Taxane based chemotherapy in the third line setting was 3.8 months. Median OS post progression on Nivolumab was 10 months. One patient remarkably had a complete response to Paclitaxel chemotherapy after progression on previous lines of treatment including immunotherapy, platinum chemotherapy and radiotherapy. We then identified a group of 13 patients with metastatic or recurrent head and neck cancer that had progressed on platinum based therapy in the era before Nivolumab was available. Median PFS after Taxane second line chemotherapy was 2.2 months. Median OS in this group after progressing on platinum treatment was 5.8 months. Conclusions: We set out to share our experience of real-world outcomes for head and neck cancer patients in the Nivolumab era. We found that our patients have shown to have an improved overall survival benefit with subsequent Taxane chemotherapy after immunotherapy compared to those who have not received immunotherapy. All fit patients should be considered for Taxane therapy post failure of Nivolumab.
Indication of adjuvant chemoradiation post neoadjuvant chemotherapy in very locally advanced borderline resectable head and neck cancer.
Authors: Das Sudeep , Patil Vijay Maruti , Noronha Vanita , Dhumal Sachin Babanrao , Joshi Amit , Menon Nandini Sharrel , Srinivas Sujay , Vallathol Dilip Harindran , D'souza Hollis , Prabhash Kumar
Published: May 2020

e18505

Background: Adjuvant chemoradiation (ACRT) is indicated in the presence of margin positivity or extranodal extension. However, indications of ACRT post neoadjuvant chemotherapy (NACT) is not well defined. At our centre, ACRT is administered in the majority of patients who undergo NACT. This analysis was performed to identify indications for the avoidance of ACRT post NACT. Methods: 160 very locally advanced borderline resectable HNSCC who underwent surgery after NACT were selected. The adjuvant treatment administered was either radiation or chemoradiation at the discretion of the joint clinic. The post-surgical tumour and nodal specimen were graded in accordance with modified tumour regression grade (MTRG). Where grade 1 indicated a complete pathological response. The primary endpoint was disease-free survival (DFS). The patients were divided into 3 biological distinct classes. Group-1 had a pathological complete response (CR) in both tumour and nodes, Group-2 had pathological CR in either tumour or nodes and Group 3 had no pathological CR. Kaplan Meier method was used for the estimation of DFS. The stratified (for groups) log-rank test was used for evaluating the impact of adjuvant radiation. Stratified Cox regression analysis was used for the calculation of hazard ratio. A p-value of 0.05 was considered significant. Results: There were 56 patients (35%) in group 3, 75 (46.9%) in group 2 and 29 (18.1%) in group 1. The overall median DFS was 89.067 months (95%CI 15.345-162.788). The 5-year DFS was 22.1% in group 3, 75.4% in group 2 and 92.3% in group 1 ( P-value < 0.0001). Adjuvant radiation was received by all patients and concurrent chemotherapy was received by 134 (83.8%) patients. Use of concurrent chemotherapy decreased the hazard of disease recurrence (HR-0.297 95%CI 0.135-0.656, P-value = 0.003). The stratified log-rank test p-value was 0.002. Conclusions: Adjuvant chemoradiation is needed after neoadjuvant chemotherapy in very locally advanced borderline resectable head and neck cancer
The impact of locoregional treatment on response to nivolumab in advanced platinum refractory head and neck cancer: The need trial.
Authors: Botticelli Andrea , Mezi Silvia , Pomati Giulia , Sciattella Paolo , Roberto Michela , Cirillo Alessio , Mammone Giulia , Cassano Alessandra , Di Dio Carmela , Cortellini Alessio , Pizzuti Laura , Ronzino Graziana , Salati Massimiliano , Vici Patrizia , Merlano Marco Carlo , Nuti Marianna , Marchetti Paolo
Published: May 2020

e18508

Background: Immunotherapy is the standard of care in the treatment of platinum-refractory recurrent/metastatic head and neck squamous cell carcinoma (R/M-HNSCC). Previous loco-regional treatment could have an impact on the immune system and response to Nivolumab. The aim of this study is to evaluate the efficacy and safety of Nivolumab in a real world population, identifying the impact of the clinic-pathological characteristics and previous treatment in prediction of early progression. Methods: This is a observational, multicenter retrospective/prospective study including patients (pts) with platinum refractory R/M HNSCC who received Nivolumab 240 mg every 2 weeks until disease progression or unacceptable toxicity, from October 2018 to October 2019. We analyzed treatment outcomes in term of early progression (within 3 months), clinical benefit, progression free survival (PFS) and overall survival (OS). To determine the influence on outcomes, the following variables were investigated: primary tumor sub-site, age, gender, ECOG, previous loco-regional treatment, previous systemic therapy, metastatic site. Results: Data from 61 pts were reviewed: 15 oral cavity, 14 oropharynx, 7 hyphofarynx, 19 larynx, 6 paranasal sinus. Median age was 66 years (29-82), 48 pts were men. Forty-nine pts (80%) had performance status (ECOG) ≥ 1 at baseline evaluation. Eleven pts (18%) had only loco-regional recurrence, while 50 pts (82%) had one or more metastatic site. 32 (52%) and 17 pts (28%) had smoking and alcohol abuse history, respectively. 44 pts (72%) received surgery followed by adjuvant radiant treatment at standard dose (28, 46%) or concomitant definitive radiotherapy (16, 26%) as upfront treatment with curative intent. With a median follow up of 4 months (range 1-11), early progression occurred in 39 pts during Nivolumab treatment (64%), while clinical benefit (stable disease and partial response) was achieved in 22 pts (36%). No G3-G4 toxicities occurred. Early progression to Nivolumab was significantly associated to previous loco-regional treatment both at univariate and multivariate analysis (p=0.003 and p= 0.04, respectively). Conclusions: Nivolumab in R/M HNSCC is effective and safe even though burdened with a high early progression rate. Loco-regional treatment, including wide neck dissection and high dose radiotherapy, may compromise the efficacy of Nivolumab, distorting the anatomy of the local lymphatic system and hindering the priming of immune response.
Comparison of circulating tumor cells and cell-free DNA in the molecular characterization of patients with head and neck cancer.
Authors: Cabezas-Camarero Santiago , García-Barberán Vanesa , De la Orden-García Virginia , Mediero-Valeros Beatriz , Díaz-Millán Isabel , Saiz-Ladera Cristina , Baliu Piqué Mariona , Gonzalo Irene , López-Cade Igor , Ocana Alberto , Díaz-Rubio Eduardo , Pérez-Segura Pedro
Published: May 2020

e18521

Background: The role of liquid biopsy in diagnosis and therapy monitoring in patients with head and neck cancer has been much less studied compared to other cancers. Our aim was to evaluate the perfomance in the isolation and recovery for molecular characterization of circulating tumour cells (CTC) of a new immunoafinity-based method and to compare it with the molecular diagnostic yield of plasma cell-free DNA. Methods: Patients with recurrent/metastatic (RM) head and neck cancer (HNC) were enrolled prospectively. Forty mililiters (ml) of plasma were collected at one or several time-points. First blood draw was always collected before starting a new therapeutic intervention or at the time of radiologic progression. For CTC detection and isolation, either anti-EpCAM or both anti-EpCAM + anti-EGFR antibodies were used. Digital PCR and castPCR were used to study KRAS and PI3KCA mutations in non-squamous HNC. A 15-gene customized NGS panel was used to characterized both CTC and cfDNA in patients with squamous HNC. Results: Between February 2016 and October 2018, 14 patients with R/M HNC were included (n = 1 local-only disease, n = 10 local and distant disease, n = 3 distant-only disease). Squamous histology (S): n = 9. Non-squamous (NS): n = 5 (1 naso-ethmoidal intestinal-type adenocarcinoma, 1 parotid gland exadenoma pleomorfic carcinoma, 2 parotid-gland salivary duct carcinomas (SDC), 1 parotid-gland high-grade neuroendocrine carcinoma). Twenty-five CTC determinations were performed. In 5 patients serial CTC determinations were performed. Median CTC was 4 (min-max: 0-49). Median CTC among 11 CTC determinations in S-HNC was 4 (min-max: 0-49). Median CTC was 3 CTC (min-max: 0-26) among the 14 determinations performed in NS-HNC. Digital PCR unveiled mutations in CTC and in cfDNA in 2 of 4 patients tested with NS histology (KRAS, PIK3CA), with one of them being concordant for the specific mutation. NGS unveiled mutations in CTC in 7/9 patients and in cfDNA in 6/9 patients, with only one loci-concordant case between CTC and plasma. Conclusions: IsoFlux detected CTC in the majority of patients with R/M HNC, regardless of the histologic type, and allowed for molecular characterization of CTC using different techniques for mutational analysis. Both NGS and digital PCR allowed for the detection in cell-free DNA of commonly mutated genes in HNC. Liquid biopsy should be more actively studied in this disease in order to better define its role in diagnosis and therapeutic monitoring.
Is there a role of functional endoscopic evaluation of swallowing (FEES) in aiding tracheotomy decannulation post oral cancer surgery?
Authors: Sahni Vibhu Ranjan , Chopra Shamit , Bharthuar Anubha
Published: May 2020

e18523

Background: A significant proportion of patients with oral cancer require perioperative tracheotomy. The altered oral anatomy post surgery significantly impairs the first and second stages of swallowing, resulting in swallowing dysfunction and potential aspiration. There is no priordata on utilization of FEES or other objective tools to predict successful tracheotomy decannulation in patients with oral cancer. Methods: This constituted a retrospective analysis of 237 patients with oral cancer treated at our institution between Feb 2017 and Dec 2019. Seventy two (30.4%)patients underwent perioperative tracheotomy. Post surgery,after excluding patients who were not considered candidates for early decannulation, 48 (65.7%) underwent FEES with the endpoint of tracheotomy decannulation. The number of FEES procedures required for decannulation was correlated with patient and disease-specific variables utilizing Chi square analysis. Results: The rate of successful decannulation was 100%. The mean number of days from tracheotomy to decannulation was 24.9. Thirty two (66.7%) patients underwent decannulation post the first FEES, notablyupon documentation of no penetration or aspiration to three bolus consistencies. However, 33.3% patients needed swallowing therapy followed by a second (18.8%) or a third (14.6%) FEES before they could be decannulated (late decannulation). No patients required a repeat tracheotomy. A significantly higher proportion of individuals at or younger than median age were decannulated earlier, compared with individuals above median age ( p= 0.01). There was no statistically significant difference between early (T1/2) and advanced (T3/4) primary lesions and timing of decannulation ( p= 0.83). The presence of comorbid diabetes mellitus did not correlate with decannulation timing ( p= 0.81). Conclusions: FEES constitutes a reliable, minimally invasive and cost-effective tool to aid successful decannulation across all stages of oral cancer. It may be indicated especially in older individuals. It helps guide swallowing therapy, and thus potentially augments quality of life by tailoring serial evaluations to aid early decannulation.
An in silico comparative planning study investigating the predicted benefit of dysphagia-optimised volumetric arc therapy (Do-VMAT), relative to standard VMAT (S-VMAT), to reduce radiotherapy-associated dysphagia (RAD) in oropharyngeal cancers (OPC).
Authors: Petkar Imran , Dunlop Alex , McQuaid Dualta , Nutting Christopher
Published: May 2020

e18540

Background: RAD is a significant treatment-related functional morbidity in OPC and is associated with irradiation of the pharyngeal constrictor muscle (PCM). This study investigated whether a novel PCM-sparing Do-VMAT technique reduced the risk of RAD, compared to S-VMAT. Methods: Twenty OPC patients who previously underwent radiotherapy (RT) to bilateral neck were selected for this retrospective study. For each patient, S-VMAT and Do-VMAT plans were created. In both arms, the mucosal and nodal tumour received 65 Gy while the remaining oropharynx and at-risk nodal levels received 54 Gy; delivered in 30 fractions over 6 weeks. For Do-VMAT, a mandatory mean dose constraint of < 50 Gy to the volume of the combined superior (SPCM) and middle PCM (MPCM) together with an optimal dose constraint of < 20 Gy to the volume of inferior PCM (IPCM), lying outside the high-dose clinical target volume, were additionally defined and optimised to minimise PCM dose. Normal tissue complication probabilities for physician-scored RAD at 6 months (RAD6M) were determined as per the model by Christianen et al in which the 2 variables were mean dose to SPCM and supraglottic larynx (SGL). Statistical analysis was performed using paired t tests. Results: All plans had adequate target volume coverage, and dose to critical organs were within acceptable parameters. Dose to the parotid and submandibular glands were similar between the 2 RT techniques. The mean integral dose was 110.8 Gy-litre (standard deviation 17.1) with S-VMAT and 103.4 Gy-litre (15.4) with Do-VMAT, p < 0.001. With Do-VMAT, the average of the mean dose to PCM, SPCM, MPCM, IPCM, and SGL were 9.3 Gy (1.4), 4.7 Gy (1.7), 7.4 Gy (3.6), 22.7 Gy (4.1), and 2.6 Gy (2.3) respectively lower than S-VMAT (p < 0.001 for all). The mean predicted risk for RAD6M was 31.0 % (4.4) with S-VMAT, and 23.9 % (3.8) with Do-VMAT, p < 0.001. The absolute reduction in estimated toxicity risk with Do-VMAT was > 5 %, the minimally clinically important difference, in every patient. Conclusions: Do-VMAT demonstrated clinically relevant reductions in the predicted risk of RAD, compared to S-VMAT, by reducing dose to the PCM in OPC. The clinical benefits of Do-VMAT is being prospectively evaluated in DARS (CRUK/14/014), a randomised phase III study.
Identifying the distant metastasis genes by next-generation sequencing panel in nasopharyngeal carcinoma.
Authors: Hu Man , Yu Jinming , Zhou Zihan , Li Peifeng , Zhang Xianbin , Zhai Limin , Fan Tingyong , Tian Shiyu , Xu Juan , Yang Xinhua , Xu Jin , Yu Shui , Wang Dongqing , Dong Wei , Cao Xiujuan , Yan Hongjiang , Sun Mingping , Ding Xiuping , Xing Jun , Zhang Peng
Published: May 2020

e18547

Background: Even though local and regional controls have been substantially improved in nasopharyngeal carcinoma (NPC) in the contemporary era of intensity-modulated radiotherapy with extensive use of combined chemotherapy, the distant metastasis becomes the major cause of treatment failure and cancer-related death. To date, the genes contributed to metastasis of NPC is still unclear. The aim of this study was to identify the genes which lead to distant metastasis. Methods: A total of forty primary nonkeratinizing NPC patients were diagnosed at Shandong Cancer Hospital in this study. The formaldehyde-fixed paraffin embedded (FFPE) taken from primary sites or metastatic lymph nodes were performed next-generation sequencing (NGS) panel (Shanghai OrigiMed Co., Ltd.) to determine variated genes, such as single nucleotide variants (SNV), copy number variants (CNV) and rearrangement. These patients were followed up until Febr. 8, 2020. The genes related to distant metastasis were identified by logistic regression. Moreover, this study compared the frequency of mutated gene between our data and Catalog of Somatic Mutations in Cancer (COSMIC) database by the Chi-square test or Fisher’s exact test. Results: The study included 31 men and 9 women. The median age of the patients at diagnosis was 47 years (range 15–71 years). With the median follow-up of 10.6 months (range 16.8–72.3 months), 7 patients had distant metastasis and 1 undergone recurrent. Notably, EMSY and MCL1 variants were contributed to NPC distant metastasis (OR = 31, P = 0.049). The top eight SNV of genes in our study were CYLD, KMT2D, BAP1, EP300, TP53, ATM, NFKBIA and SPEN. When compared to COSMIC database, the mutant frequencies of CYLD, EP300 and BAP1 in our study were significantly higher than that of COSMIC database. However, the mutant frequencies of IDH2 and KMT2C were significantly lower than COSMIC database. Conclusions: This is the first study which suggests that EMSY and MCL1 variants were involved in the metastasis of NPC. The study identified 5 genes, which mutation frequency is significantly different from the COSMIC database. The study provided a molecular basis for a comprehensive understanding of, and exploring targeted therapies for nasopharyngeal carcinoma.