bluuebunny/crossref_metadata_2025 huggingface dataset:
Preclinical antitumor and antiangiogenic activity of a metronomic schedule of cisplatin against human transitional cell carcinoma (TCC)
Authors: Jian W. , Levitt J. M. , Lerner S. P. , Sonpavde G.
Published: August 2020

e16018

Background: Conventional cisplatin every 3 weeks is frequently precluded in patients with TCC due to renal dysfunction. A metronomic schedule of other chemotherapeutic agents demonstrates anti-angiogenic and anti-tumor activity coupled with better tolerability. A rationale can be made to preclinically evaluate the activity of a metronomic (weekly or 3 days a week) schedule of cisplatin in a preclinical system of TCC. Methods: The activity of cisplatin was assessed in vitro against HUVECs (human umbilical vein endothelial cells). MTT, flow cytometry with Annexin-FITC and scratch assays were employed to assess proliferation, apoptosis and migration, respectively. The activity of cisplatin was evaluated in vivo in murine xenograft models of TCC. The subcutaneous xenografts included 5 × 106 RT4 or 5637 human TCC cells injected into 6- to 8-week-old female athymic BALB/c nu/nu mice. Cisplatin was administered 4 mg/kg IP (intraperitoneal) weekly for up to 6 weeks and compared with untreated mice. Then, 3 groups of tumor-bearing mice received either no therapy, cisplatin 6 mg/kg weekly or cisplatin 2 mg/kg for 3 days a week for up to 6 weeks. Tumor size is measured twice a week. Nephrotoxicity is assessed by serum creatinine and kidney histopathological examination. IHC (immunohistochemistry) of xenografts is performed to measure proliferation (ki-67), apoptosis (cleaved caspase-3) and angiogenesis (CD31). Results: Cisplatin demonstrated significant anti-proliferative, anti-migration and pro-apoptotic activity against HUVECs in vitro. Cisplatin 4 mg/kg weekly inhibited tumor growth, induced higher apoptosis and down-regulated angiogenesis and proliferation in vivo compared to controls. Results from the experiment comparing cisplatin 6 mg/kg weekly with 2 mg/kg 3 days a week (i.e. more metronomic, with potentially more anti-angiogenic and anti-tumor activity and less nephrotoxic) will be presented. Conclusions: A metronomic schedule of cisplatin inhibits tumor growth and demonstrates anti-angiogenic activity in a preclinical model of human TCC. The clinical evaluation of a metronomic schedule of cisplatin may be warranted.

No significant financial relationships to disclose.
External validation of preoperative nomograms for predicting pathological stage of prostate cancer: Analysis of 716 Japanese cases
Authors: Kanao K. , Shinojima T. , Nakashima J. , Ohigashi T. , Kikuchi E. , Miyajima A. , Nakagawa K. , Oya M.
Published: August 2020

e16078

Background: For the purpose of predicting pathological stage of prostate cancer, Partin et al have developed preoperative nomograms (Partin Tables). Partin tables were modified and updated twice to reflect a more contemporary condition of prostate cancer stage at diagnosis. Recently similar Tables using 1188 Japanese patients were also developed. Although the characteristics of prostate cancer are thought to vary between Asian and Western patients, there are few studies to validate the prognostic accuracy of Partin tables in Asian patients and there is no study to validate three Partin table simultaneously. In this study we evaluate the validity of thee Partin Tables and Japanese Tables for our 716 of Japanese cases. Methods: Seven hundred sixteen patients were analyzed retrospectively who underwent radical prostatectomy in our institute without neoadjvant endocrine therapy. In four Tables (Partin 97, 01, 07 and Japanese Tables) the patient's distributions were evaluated and the fitness for each models were also evaluated using AIC (Akaike's information criteria). The probabilities of organ confined disease for each case were calculated from four nomograms and external validation was performed using ROC analysis and calibration. Results: Preoperative clinical stage of our cases were 587 with T1c, 140 with T2a, 20 with T2b and 63 with T2c. PSA at diagnosis was 10.45±0.60 (mean±SE). AIC of each Tables was 975.0 in 97 Tables, 974.3 in 01 Tables, 975.4 in 07 Tables and 973.6 in Japanese Tables. The area under the ROC curve (AUC)of each Tables was 0.619 in 97 Tables, 0.623 in 01 Tables, 0.614 in 07 Tables and 0.614 in Japanese Tables. There were no difference of calibration plots in four Tables and in general actual probabilities of organ confined were lower than predicted probability. Conclusions: This study showed that four nomograms have no difference in discrimination and prediction ability to our cases, but when we use these nomograms it is necessary to estimate the probability to be low than predicted probability.

No significant financial relationships to disclose.
Oral vinorelbine as a fixed-weekly schedule in taxanes-refractory advanced HRPC: A single institution experience
Authors: Rodriguez Garzotto A. , Sepulveda J. , Cortijo A. , Garcia L. , Garcia Rodriguez I. , Ciruelos E. , Rodriguez Antolin A. , Cortes-Funes H. , Castellano D.
Published: August 2020

e16084

Background: Vinorelbine (VRL) has been shown to be active in hormone-refractory prostate cancer (HRPC). Oral formulation of VRL represents a significant advance in the treatment of advanced cancer. The recommended doses are 60–80 mg/m2(d1–8 q3wks).We evaluated efficacy and toxicity of different VRL schedule administered as a fixed-weekly dose of 60 mg/m2. The purpose of this study was to evaluate the toxicity profile and efficacy of this schedule in terms of PSA response, objective response and clinical benefit (CB) response. Methods: Pts characteristics were: PS 0–2, adequate bone marrow, liver and renal functions. Oral VRL was adminestered at weekly dose of 60 mg/m2 until disease progression/intolerable toxicity. PSA response was defined as a >50% fall in PSA from baseline, confirmed by a second PSA value 4 or > weeks later. Pts with measurable soft tissue disease met traditional guidelines for tumour responses. Progression was defined by objective disease progression or PSA increase of >50% above nadir or >25% above baseline. Pts were monitored clinically and with serial PSA measurements every 1 week. Results: Thirty seven pts with progressive HR metastatic prostate cancer were evaluated. Mean (range) age was 67 years (50–88), median PSA level was 90 ng/ml (1- 4314), and median Gleason score was 7 (6–9). 23 (62%) pts had previous taxane chemotherapy and 14 pts (38%) were chemo-naive. Pts received a mean of 5.5 cycles (1cycle=3wks) (range:1–24). Median follow-up was 12 months. Thirty three of 37 Pts (97%) achieved a decline in serum PSA. CB response was achieved in 15 out of 37 pts(40%). The PSA response was observed in 13 pts (35%). Objective response was not observed and only 6 pts showed SD (16%). The relative dose-intensity was 94%. There were no reported grade 3–4 toxicities. Only 1 treatment discontinuation was observed (esopahgitis g2). Toxicities consisted primarily of g2 anemia (25%) and mild nausea (32%). Conclusions: Oral Vinorelbine administered as a fixed-weekly schedule of 60 mg/m2 is a safe regimen in pts with advanced HRPC. This regimen of oral vinorelbine is an effective and well-tolerated treatment in this setting, despite a major dose-intensity administered. Further studies will be evaluated in chemo-naive and/or elderly population.

No significant financial relationships to disclose.
Phase II study of sorafenib combined with gemcitabine and 5-fluorouracil in patients with metastatic renal cell carcinoma: Preliminary results
Authors: Hongyun L. , Zhihong C. , Xiangqing Y. , Lu S. , Chuanliang C. , Xinan S. , Lin S. , Jun G.
Published: August 2020

e16093

Background: The tyrosine kinase inhibitors sorafenib and sunitinib have been approved for use in patients with advanced RCC and have supplanted immunotherapy as first-line therapy. Nevertheless, complete responses have been observed only rarely with these agents and only 10% of patients experience PR. The vast majority of responding patients will ultimately progress despite continued therapy. In order to improve the objective response rate and the durability of those responses in patients, we conducted a single-institution, single-arm phase II trial of gemcitabine and 5-fluorouracil (5-FU) combined with sorafenib in patients with RCC. Methods: Eligibility criteria included advanced, histologically confirmed RCC; age >18 years; ECOG PS ≤ 2, adequate bone marrow, renal and hepatic function; measurable/evaluable lesions. Gemcitabine was administered at 1,000 mg/m2 over 30 min i.v. on days 1 and 8, followed by 5-FU 400 mg/m2 i.v. bolus on day 1 and 1,200 mg/m2/day × 2 days continuous infusion (28-day cycle). From day 1 of cycle 1, 400 mg sorafenib was continuously given twice daily. The sample size of 21 patients was sufficient to provide 80% power to detect an objective response rate that was greater than 10% with significance that 0.05 level. Results were expressed as mean±SD or median ± 95% CI. The primary study endpoint was objective response rate and the secondary were toxicity, progression-free survival and overall survival. Results: Patients (n = 21) were enrolled from May 2006 to Dec. 2007. The rate of objective response and disease control (including stable disease, complete responses and partial responses) were 38% (95% CI, 18–62%) and 86% (95% CI, 64–97%), respectively. Among them, there is 1 complete response and 2 pts occurred completely liquefaction deliquesce in metastatic lesions. The median PFS time is longer than 13 months, with 6/21 patients remaining progression free at 2008.12.26 the data were compiled for this report (three are longer than 26 months and there other three longer than 13 months ). The median OS time have not yet been reached, because of the amount of censoring data. Conclusions: The combination of sorafenib with gemcitabine and 5-FU shows promising activity for patients with metastatic RCC.

No significant financial relationships to disclose.
Effect of sorafenib on chemotherapy resistance and refractoriness in castration-resistant prostate cancer (CRPC)
Authors: Nabhan C. , Tolzien K. , Lestingi T. M. , Galvez A. , Bitran J. D.
Published: August 2020

e16105

Background: There is no standard for CRPC once chemotherapy fails. In studies employing docetaxel (D), 35–39% of pts did not complete therapy due to progression and only 45–50% had a PSA response. This implies that many pts develop resistance to D. Sorafenib is a multi kinase inhibitor with antiangiogenesis properties. We hypothesized that sorafenib could overcome chemotherapy resistance in these pts. Methods: Eligible pts must have progressed while on either D or mitoxantrone (M). They received sorafenib at 400 mg orally twice/daily in addition to the chemotherapy agent they were on. Sorefinib/chemotherapy combination was given for a maximum of 6 cycles followed by sorafenib monotherapy until progression. Primary end point was safety of the sorafenib/chemotherapy combination. Secondary end points included the overall clinical benefit calculated as the sum of complete response (CR), partial response (PR), and stable disease (SD), toxicity, and time to disease progression (TTP). Results: To date, 15 pts have been enrolled; 14 are evaluable. Eleven pts were on D and 4 on M. Median age was 68 (range 61–83), median PSA was 111.2 ng/ml (13.6–1703.9). Nine pts (60%) had visceral and bone disease. Median PSA-DT pre-study was 2 months (0.5–6) and median time from last chemotherapy to starting study was 4 weeks. Median number of given cycles was 6.5 (2–12). Six pts did not require dose reduction, 2 others were re-escalated to the full dose. Sorafenib was safely combined with chemotherapy with 6 pts experiencing grade 3 fatigue, 3 developing grade 3 hand/foot syndrome, and 1 experiening grade 3 diarrhea. Eleven pts (73%) had SD radiographically that lasted a median of 6.7 months. In all, 6 out of 14 pts (42%) had a PSA decline after adding sorafenib and 3 (21%) had stable PSA. Of these 9 pts (PR+SD), 2 never doubled their PSA. Two pts had PSA decline after withdrawing sorafenib. Median TTP for PSA was 3.75 months. PSA responses did not correlate with radiographic changes or clinical benefit. With a median follow-up of 8 months, 5 pts (33%) remain alive with 1 continuing on therapy without progression. Conclusions: Sorafenib overcomes chemotherapy-refractoriness and failures in CRPC.

[Table: see text]
Risk factors for thromboembolic events in testicular cancer patients receiving chemotherapy
Authors: Shim K. , Potvin K. R. , Mills K. , Whiston F. , Stitt L. , Winquist E.
Published: August 2020

e16109

Background: Cancer patients are at increased risk for thromboembolic events (TTEs), and those receiving chemotherapy are at even greater risk. Clinical experience and the literature have suggested that men receiving cisplatin-based chemotherapy for metastatic germ cell tumors are at particularly high risk. As TTEs can be fatal and treatment is curative, the stakes are high. Despite this, prophylactic anticoagulation (PA) is not routinely used. Methods: All men treated with cisplatin-based chemotherapy for metastatic germ cell cancer at the London Regional Cancer Program from January 1978 to December 2007 were identified from electronic databases. Data including type and timing of TTEs were extracted by retrospective chart review. Multivariable analyses were used to identify predictors of TTEs. Results: 196 eligible patients were identified with median age 31 years (range, 15–75). No patients received PA. Thirty-two TTEs were identified in 29 patients for an overall incidence of 14.8% (95% CI, 9.8–19.8%). The majority of events were deep venous thromboses, and five patients died due to TTE or its complications. Sixteen of the patients with TTE (55.2%) were diagnosed while on treatment (defined as TTE within 6 months of chemotherapy initiation); 8 (27.6%) had their TTE prior to, and 5 (17.2%) after this time period. Age greater than 30 years (OR = 3.02; 95% CI, 1.10–8.33; p = 0.033) and elevated LDH (OR = 1.93; 95% CI, 1.07–3.48; p = 0.029) were independently associated with an increased risk of TTE. If both adverse risk factors were present, the risk of TTE on treatment was 21.7% (95% CI, 9.8–33.7%). If neither were present, the negative predictive value was 97% (95% CI, 92–100%). Conclusions: The overall TTE incidence rate of 14.8% is consistent with prior reports (8.4–19%). The risk of TTE appears greatest during chemotherapy and shortly thereafter, and nearly one in 10 patients in this group had a TTE. These data support the concept of PA for selected patients starting chemotherapy for metastatic germ cell cancer. However, the efficacy of PA and risk of hemorrhage in this group is unknown. In this cohort, patients under 30 with normal LDH were at very low risk for TTE. Confirmation of these findings to help guide the study and optimal use of PA should be pursued.

No significant financial relationships to disclose.
The value of PET/CT with 18F-FLT and 18F-FDG in the management of metastatic germ cell tumors (GCT): A pilot study
Authors: Hartmann J. T. , Aschoff P. , Dittmann H. , Lichy M. , Mayer F. , Reischl G. , von Weyhern C. , Kanz L. , Claussen C. D. , Pfannenberg C.
Published: August 2020

e16142

Background: The purpose is to assess the ability of [F-18]-3’-Fluoro-3’-deoxythymidin (FLT), a cell proliferation marker, for early response monitoring and prediction of histology of residual tumor masses in patients (pts) with metastatic GCT in comparison to the standard tracer F-18-FDG, CT-scans and tumor markers. Methods: 11 male pts, age 23–48 yrs, with metastatic GCT were evaluated with both FDG- and FLT-PET/CT prior to chemotherapy (CTh), after the first cycle (early response) and 3 weeks after completion of induction CTh. PET was analyzed visually and quantitatively. The results were validated by histopathology of resected residual masses after CTh in 7 pts or by clinical follow-up for at least 6 mos in 4 pts. Presence of necrosis was judged as responder, as well as CR/PRm- within a minimum progression-free interval (PFI) of 6 mos. In case of multiple resections, the worse histology was taken into account. Regarding early tumor response EORTC criterias were used. Results: 8 out of 11 pts had a PFI > 6 mos (range, 206–1337 days). Examination of resected masses revealed necrosis in 3/7, teratoma in 2/7 as well as 2/7 pts with viable tumors. Prior to CTh the reference lesions showed increased FDG uptake (SUVrange/mean, 2.9–15.0/8.8) in all pts but moderate FLT uptake (SUVrange/mean, 1.7–9.7/3.7) in 10 out of 11 pts. SUVavg decrease in early response FDG monitoring was 64% in responders and 60% in non-responders (p = 0.8), as well as 57% vs. 48% for FLT (p = 0.5), respectively, and 85% vs. 72% (FDG, p = 0.1) and 67% vs. 65% (FLT, p = 0.8) in the final monitoring. Results of early and final response were inconsistent in 6/11 pts in FDG and in 4/10 pts in FLT-PET. In 2 pts with teratoma false negative results in both FDG- and FLT-PET have been seen. The sensitivities, specificities, positive and negative predictive values (%) of FDG and FLT-PET for early and final response monitoring were 60/33/43/50, 60/80/75/67, 20/100/100/60, and 0/100/0/50, respectively. Conclusions: PET negative residual masses after CTh of metastatic GCT still require resection, since the low negative predictive value of FDG-PET cannot be improved by application of the proliferation marker FLT.

No significant financial relationships to disclose.
Expression and circulating levels of lymphangiogenic parameters in renal cell cancer: Implication for antiangiogenic treatments
Authors: Mouawad R. , Comperat E. , Spano J. P. , Izzedine H. , Cajfinger F. , Deray G. , Capron F. , Khayat D.
Published: August 2020

e16144

Background: Vascular endothelial growth factors C, VEGF-D and VEGFR-2, R-3, are overexpressed in different malignancies and associated with lymph node metastasis and poor prognosis. In renal cell cancer (RCC) lymphatic tumor spread exist but data focusing on lymphangiogenesis are rare. Since the VEGF-C/VEGF-D/VEGFR-2, R-3 axis appears to be the signaling pathway for tumor-induced lymphangiogenesis and an attractive target for therapeutic intervention; we analyzed the expression and the presence of the soluble forms in 30 RCC patients and results were correlated with clinicopathological parameters. Methods: Tumor and sera from 30 RCC patients (20 clear cell (ccRCC)&10 papillary (pRCC) were included in this study. The expressions of VEGFR-2,R-3 &VEGF-C,-D expressions on tumor were evaluated by immunohistochemestry. Using ELISA assays, sVEGFR-2, R-3 &sVEGF-C,-D were measured in sera of RCC patients in comparison to 20 healthy controls. Results: In overall patients, a high expression of VEGF-C,-D and their receptors were observed in more than 55%of the patients as compared to the negative control. Regarding circulating VEGF-C,-D, R2, R-3 they were variable in all samples from either patients or healthy donors. Only median sVEGF- R3 level was significantly higher (p=0.005) in RCC patients as compared to healthy donors. VEGF-C and VEGF-D expression was significantly correlated (r’=0.43, p=0.02) with each other but not with the expression of its receptors. An inverse correlation between Flt-4 expression & its soluble form was noted (r=-0.33 p=0.040). The expression of VEGF-C, VECF-D and sVEGFR-3 were significantly higher in pRCC than ccRCC (p=0.02, 0.01 and 0.035 respectively). The expression of VEGFR-2,VEGFR-3 were not different between the subgroups (p=0.11). Furthermore, no correlation with clinicopathological parameters was shown in either overall patients or in the two subgroups. Conclusions: we showed that in RCC the lymphangiogenic factors are expressed or present as soluble form, a different expression pattern in ccRCC and pRCC existe. Therefore, further studies are necessary to determine if lymphangiogenesis can play a role as a prognostic tool or a target for therapeutic intervention in renal cell carcinoma.

No significant financial relationships to disclose.
Molecular profiling in the diagnosis of synchronous primary cancers of the endometrium and ovary
Authors: Soliman P. T. , Celestino J. , Finklelstein S. , Broaddus R. , Westin S. , Schmeler K. M. , Lu K. H. , Coleman R. L.
Published: August 2020

e16500

Background: Synchronous primary cancers of the endometrium and ovary (SYNCH) have a better prognosis than either primary endometrial or ovarian cancer with metastasis (MET). Distinguishing SYNCH from MET can be a challenge when the neoplasms share similar histologic features. To date, histologic characteristics are used to make this distinction and guide treatment decisions. The purpose of this study was to determine if objective discrimination using an integrated molecular approach can assist in making this distinction. Methods: Paired tumor samples from 16 SYNCH and 11 MET were sent for mutational profiling. 13 samples were sent as blinded duplicates for internal validation. The mutational profile for each neoplasm was determined using PCR and quantitative genotyping for a panel of LOH markers targeting 1p,3p,5q,9p,10q,17p,17q,21q,22q and k-ras-2 exon 1 DNA sequencing for point mutational change. The paired samples were then re-defined as SYNCH versus MET based on the profile results. Survival was compared using Kaplan-Meier. Results: The results are in the table. All of the duplicate samples had the same molecular profile results. Median survival based on pathologic diagnosis was 106 months in SYNCH versus 37 months in MET (p=0.07). The median survival was 110 months in both groups based on molecular profiling results. For patients with a diagnosis of SYNCH by both pathology and molecular profiling median survival was 117 months. For those with a pathologic diagnosis of SYNCH but metastasis on molecular profiling survival was 129 months. Conclusions: Molecular profiling to distinguish synchronous primary cancers from either primary endometrial or ovarian cancer with metastasis, is currently being evaluated. In this study, the pathologic diagnosis was a better indicator of survival than a diagnosis based on molecular profiling alone. Further studies are being performed to determine the role of molecular profiling in women who are thought to have synchronous primary cancers of the endometrium and ovary. [Table: see text]

[Table: see text]
A Gynecologic Oncology Group study of frequent copy number aberrations in DNA repair genes and other genomic regions in stage I serous ovarian cancers
Authors: Pejovic T. , Gaile D. P. , Darcy K. M. , Liu S. , Shepherd L. , Rodgers W. H. , Kohn E. , Mannel R. , Birrer M. J. , Nowak N.
Published: August 2020

e16504

Background: A proof of principle array-based comparative genomic hybridization (aCGH) analysis was performed in archival formalin-fixed and paraffin-embedded (FFPE) stage I ovarian cancers (EOC) to determine if frequent (>40%) copy number aberrations (CNAs) can be detected in DNA repair genes including the Fanconi anemia complementation group (FANC) and RAD51 families compared with the rest of the genome. Methods: Tumor DNA was isolated from 22 serous cancers from the GOG-175 virtual tissue bank. RPCI 19K BAC arrays were hybridized (GeneTAC HybStation) and scanned (Gene Pix 4200AL Laser Scanner). Spot fluorescence values were quantified using ImaGene, vetted for quality and loess corrected with adjustments for chip-specific spatial effects. The genome was segmented to identify regions with common copy number means (DNAcopy software). Posterior aberration probabilities for the regions were obtained using CGHcall and data was visualized and annotated using iGenomicViewer in R. Results: Several genes associated with the Fanconi DNA-damage response pathway were frequently altered in stage I serous ovarian carcinomas. A RAD51 homology DMC1 was amplified in 55% of the specimens. Genomic losses were observed in FANC-D1 (BRCA2), and RAD51L3 in 41%, and 27% of specimens, respectively. In contrast, frequent genomic losses or gains involved 13q33.1; 13 q21.31; 17p12; 17q22; 18q12.3; 9p11.2; 9p22.2–22.3; 9q33.1; 8p23.2; 21q21.3; and 5q14.2; or 8q24.3; 3q29; 12p11.1; 17q25.1; 17q25.3; 20q13.33; 20q11.21; 20q11.23; 19p13.13; and 19p13.2, respectively. Conclusions: The GOG-0175 virtual tissue bank yielded high quality DNA for detecting and mapping CNAs in archival FFPE specimens with high resolution. Frequent genomic losses and gains were observed in DNA repair genes and other genomic regions in stage I serous ovarian cancer which may promote genomic instability, resistance, metastasis and aggressiveness of this disease.

No significant financial relationships to disclose.
Use of amplification of the 8q24 and 20q11–13 loci to predict progression-free survival of advanced epithelial ovarian cancer patients receiving standard therapy
Authors: Tominaga E. , Tsuda H. , Arao T. , Nishimura S. , Chiyoda T. , Nomura H. , Kataoka F. , Susumu N. , Aoki D. , Nishio K.
Published: August 2020

e16526

Background: The purpose of this study was to identify genes that predict the progression free survival (PFS) of advanced epithelial ovarian cancer (aEOC) receiving standard therapy. Methods: We performed expression analysis using GeneChip (Human Genome U133 plus 2.0 Array) in aEOC cells produced by laser-based microdissection. Thirty three aEOC patients (stage IIc: 4, III: 19, IV: 10; serous adenocarcinoma: 21, endometrioid adenocarcinoma: 5, undifferentiated: 7) were included in this array study. All cases received staging laparotomy, cytoreductive surgery, and adjuvant chemotherapy (carboplatin + paclitaxel) as primary therapy. Results: Class comparison analysis between groups of NED (no evidence of disease) and non-NED identified 46 genes that exhibited significant differences (p < 0.001). Among them, 6 (13%) genes are located in 8q24 and 9 (19.6%) genes are located in 20q11–13. Finally, we focused on 8q24 and 20q11–13 loci, and confirmed array data using real-time quantitative PCR in 94 validation sets. The validation showed that ZNF7, MAF1, ADRM1, and GNAS amplification was related with PFS (p < 0.05, respectively). Conclusions: The amplification of 8q24 and 20q11–13 can predict the PFS of aEOC and these genes may be new biomarkers for aEOC.

No significant financial relationships to disclose.
Extent of cervical involvement in endometrial cancer as a predictor of outcome
Authors: Ferriss J. S. , Brix W. , Henretta M. , Hanley K. , Stoler M. , Duska L. , Modesitt S.
Published: August 2020

e16566

Background: Endometrial cancer will affect 40,000 women this year. Extent of myometrial invasion and presence of cervical stromal disease are risk-factors for metastasis and recurrence. Uterine cervical involvement is often not known in advance of surgery, and superficial involvement may not be seen at frozen section. The objective of this study was to determine if the extent of cervical invasion is a predictor of outcome. Methods: The institutional cancer registry was searched for cases of stage II uterine cancer from 1996–2006. Inclusion criteria were endometrioid histology and clinical data and pathology available for evaluation. Demographics, extent of surgery, tumor grade, depth of myometrial invasion, presence of lymph-vascular space invasion (LVSI), and last follow up were collected. In addition, a gynecologic pathologist evaluated all slides to determine depth of cervical stromal invasion. Statistical analysis to compare predictors of outcome was performed. Results: There were 800 cases of endometrial cancer diagnosed from 1996–2006, 75 (9%) were stage II. Fifty two cases met all inclusion criteria. Mean age at diagnosis was 63.4 years. Mean BMI was 31.6. Ninety four percent were white, 4% black, and 2% Asian. All patients had a hysterectomy, 6 (11.5%) had a radical hysterectomy and 36 (69%) had lymphadenectomy performed. Eighteen (34.6%) were stage IIA and 32 (61.5%) were IIB. LVSI was seen in 15 (28.8%) cases. On pathologic review, 37.5% had no cervical stromal invasion, 42.5% had invasion of less than half and 20% had invasion of more than half of the cervical stroma. Forty patients (77%) received adjuvant radiation. There were 8 recurrences and 6 disease-related deaths. The mean follow up period was 30 months. Extent of cervical invasion did not correlate with recurrence or survival. Factors associated with increased risk of recurrence were: LVSI (p = 0.017), lack of lymph node sampling (p = 0.035), and age >55 years (p = 0.027). Women with and without recurrence were compared and did not significantly differ. Conclusions: In this study with pathologic review, extent of cervical involvement in stage II endometrial cancer was not associated with increased risk of recurrence or death. Age >55 years, lack of node sampling and presence of LVSI were predictors of recurrent disease.

No significant financial relationships to disclose.
Current management of borderline ovarian tumors: A multicenter survey of 323 clinics in Germany, on behalf of the North-Eastern German Society of Gynecological Oncology (NOGGO)
Authors: Chekerov R. , Coumbos A. , Sehouli J. , Schaedel D. , Oskay-Oezcelik G. , Lichtenegger W. , Kuehn W.
Published: August 2020

e16568

Background: The aim of this survey was to analyze the standard of care in diagnostic, surgery, chemotherapy and aftercare management of patients with Borderline tumor of the ovary (BOT) in Germany. Methods: A structured questionnaire comprising different dimensions of treatment of BOT was sent to all 1,114 gynecological departments in Germany. The questionnaire could be returned anonymously. Results: The overall response rate was 29.0% (323 departments). The most departments were on secondary care (71.8%), tertiary care (23.2%) or university hospital (5.0%) level. The most clinicians performed not more than 5 BOT operations (89.2%) per year. 93.2% of the gynecological departments used additional preoperative diagnostic procedures to the classical bimanual examination and vaginal ultrasound in a case of unclear ovarian tumor: CA-125 or CEA detection (95%), CT-scan (76%), Doppler ultrasound (66%), MRI (36%), or PET-CT (1.7%) techniques. In university hospitals (87%), tertiary care (80%), secondary care (68%) and most of the general practitioners’ hospitals (64%) a regular fresh frozen section was the intraoperative diagnostic standard. For diagnosis of BOT mostly laparotomy (48%) and laparoscopy (15%) were performed, whereas 19% used a diagnostic laparoscopy, followed by laparotomy for completion in a second intervention or switch from laparoscopy to laparotomy in the primary surgical session (18%). In young women with desire to preserve fertility clinicians performed much seldom unilateral salpingo-oophorectomy (92%) and only in 53% biopsies of the contra lateral ovary and in 67% peritoneal biopsies. Generally biopsies of the contra lateral ovary were performed in 4% to 53% of all patients. Chemotherapy was the second therapy option (64%) after surgery (97%) for BOT, mostly favored in “high-risk” patients with tumor residual, micro invasion or invasive implants. Conclusions: These data demonstrate a high clinical unsureness in the clinical management of borderline tumors of the ovary.

No significant financial relationships to disclose.
Role of perfusion computed tomography (CTp) for pretherapy assessment and induction chemotherapy monitoring (IC) in patients with squamous cell carcinoma (SCC) of the head and neck
Authors: Petralia G. , Preda L. , Chiesa F. , Nolè F. , d'Andrea G. , Giugliano G. , Verri E. , Cossu Rocca M. , Bellomi M.
Published: August 2020

e17015

Background: Reliable assessment of the response to IC is required to stratify further treatments, as responders are considered the best candidates for organ preservation strategies. We evaluated the role of CTp for pre-therapy assessment and IC monitoring in patients with SCC of the head and neck. Methods: From November 2004, 28 consecutive patients with locally advanced SCC of the head and neck were enrolled, undergoing CTp and volumetric CT before and after IC with cisplatin, administered at a dose of 100 mg/m2 iv, on day 1, and 5-fluorouracil, administered at a dose of 1,000 mg/m2 ci from day 1 to day 5, q3wks for 2 or 3 cycles. Perfusion parameters were calculated for tumor: blood flow (BF), blood volume (BV), mean transit time (MTT) and capillary permeability-surface (PS). The Wilcoxon rank sum test was used to test for differences in the pre-therapy perfusion parameters between the different tumor grades, as well as between responders and nonresponders to IC. The post-therapy perfusion parameters were compared with the pre-therapy ones by the Wilcoxon signed rank test and percent changes in perfusion parameters were correlated with percent changes in tumor volume calculated by volumetric CT after IC by the Spearman correlation coefficient. Results: Pre-therapy BF was significantly higher in G3 tumors, compared to G1 and G2 (p = 0.01) and G2 tumors (p = 0.03), and pre-therapy BV significantly higher in responders than in nonresponders (p = 0.01). Of the 20 patients who underwent post-therapy CTp, the 17 responders had significant reduction of BF (p = 0.003) and BV (p = 0.014) and increase of MTT (p = 0.04) in the post-therapy CTp, whereas the 3 non responders no significant changes in perfusion parameters. In the 17 responders, percent reduction in BF and BV showed correlation (Spearman R = 0.71, p = 0.0013 and R = 0.82, p = 0.00005, respectively) with percent reduction in tumor volume after IC. Conclusions: In our cohort of patients with SCC of the head and neck, CTp showed potential for pre-therapy assessment, as well as for IC monitoring; further studies are required to confirm our preliminary results.

No significant financial relationships to disclose.
Can serial PET/CT imaging during and after chemoradiation treatment assist in individualizing therapy for patients with squamous cell cancer of the head and neck?
Authors: Greven K.
Published: August 2020

e17022

Background: PET/CT imaging with FDG has the potential advantage over conventional imaging of demonstrating metabolic changes in tumors early in the course of chemoradiation which may aid in individualization of therapy for patients. Methods: Sixteen patients with stage III/IV head and neck cancer were prospectively entered on a study to evaluate the role of PET/CT between March 2006 and July 2007. Enrolled patients were treated with chemoradiation (CRT) and had a series of 5 PET/CT scans in the treatment position at the initiation of therapy, 2 and 4 weeks after initiation of chemoradiation and then 6 weeks and 3 months after completion of treatment. The max standard uptake values (SUV) were recorded in the primary tumors. In addition CT imaging was examined and the maximum dimensions of the primary tumor were recorded. Results: Three patients have recurred at the primary site and follow-up ranges from 15–30 months. Twelve patients had decreasing SUV 2 weeks after initiation of CRT, one stayed the same, and two increased. The change ranged from a 75% decrease to a 21% increase compared to the initial scan. All patients had stable or decreasing SUV 4 and 6 weeks after initiation of therapy (range: 0 to 100% decrease). The change in SUV at 2 weeks, 4 weeks, post RT 6 weeks and 3 months compared to baseline for the 3 patients with local recurrence and the 13 patients who remain disease free were -7%, -62%, -50%, and -16% compared to -34%, -62%, -77%, and -81%, respectively. Higher PET values were significantly associated with a higher risk of recurrence (p = 0.04). In contrast CT imaging demonstrated that tumor measurements at 2 weeks, 4 weeks, post RT 6 weeks, and 3 months steadily decreased in both groups with mean changes in the recurrence group and in the locally controlled group of -11%, -46%, -77%, and -100% and -47%, -57%, -73%, and -99%, respectively. CT measurements were not associated with the risk of recurrence (p = 0.72). Conclusions: Changes in SUV from PET/CT were significantly predictive of tumor recurrence compared to CT imaging alone. If this observation can be verified in a larger cohort of patients, individualization of treatment based on PET/CT changes may be possible in order to improve outcomes for these patients.

No significant financial relationships to disclose.
ERCC-1 (E) expression and its effect on survival in patients (pts) receiving concurrent cisplatin (C) and radiation (R) for locally advanced head and neck cancer (HNC)
Authors: Lan C. T. , Amirkhan R. H. , Gray T. , Xie Y. , Dowell J. E.
Published: August 2020

e17033

Background: E is a DNA repair gene involved in the nucleotide excision repair pathway. Overexpression of E has been associated with resistance to C in patients with ovarian, gastric, and lung cancer. We retrospectively analyzed tissue from HNC pts who received concurrent C and R to determine if E expression was a significant independent predictor of survival. Methods: Eligible HNC pts had squamous cell histology and received definitive concurrent C and R at the Dallas VAMC. Tissue was immunostained for E using ERCC-1,clone 8F, 1:100 dilution (Abcam, Cat#ab2356, Cambridge, MA) diluted in ChemMate buffer (Ventana Medical Systems, Tucson, AZ) on a BenchMarkXT automated immunostainer using the UltraVIEW system with horseradish peroxidase and diaminobenzidine (DAB) chromogen (Ventana Medical Systems, Tucson, AZ) per the standard protocol of the UT Southwestern Pathology Immunohistochemistry Laboratory. E scoring was determined by 2 pathologists blinded to clinical outcomes. Scoring was as follows: 0 = 0% of tumor nuclei were positive, 1+ = less than 50%, 2+ = 50–75% and 3+ = 75–100%. Results: 73 consecutively treated patients were analyzed. Median age 59 (range 41 - 80); 99% male; 7% stage II, 19% stage III, 73% stage IV; primary site - 4% oral cavity, 56% oropharynx, 14% hypopharynx, 23% larynx, 3% nasopharynx; Tumor grade - 60% moderately differentiated, 4% well differentiated, 15% poorly differentiated, 21% not specified; Performance status 0–25%, 1–45%, 2–8%, unknown-22%; E scoring was 0 in 0%, 1+ (14%), 2+ (42%), 3+ (44%). In univariate analysis, E staining 3+ was not predictive of survival with a hazard ratio (HR) of .796 (95% CI .44–1.43; p = 0.44). In multivariate analysis, the only significant predictor was hypopharynx with a HR of 3.18 (95% CI 1.02–9.88; p = 0.046). HR for age > 60 was 2.16 (95% CI .96–4.86; p = 0.06). E staining 3+ was not predictive of survival with a HR of .69 (95% CI .3–1.56; p = 0.37). Median survival (MS) for the whole group was 2.8 years (y); 5y survival - 41%. MS for the E 3+ pts - 2.1y; 5y survival 38%. MS for the E < 3+ pts - 2.9y; 5y survival 44% (p = not significant). Conclusions: In our retrospective review of HNC patients receiving concurrent C and R, E staining was not a significant predictor of survival.

No significant financial relationships to disclose.
VTE prophylaxis across the continuum of care in U.S. cancer patients
Authors: Amin A. , Lin J. , Ryan A.
Published: August 2020

e17510

Background: The period of VTE risk in cancer patients extends beyond the hospital stay. This analysis evaluated VTE prophylaxis patterns for US cancer patients across the continuum of care. Methods: Premier's Perspective inpatient data were cross-matched with Ingenix LabRx outpatient data from the I3 database (January 2005-December 2007) to assess VTE prophylaxis patterns in medical cancer patients at risk of VTE (according to the American College of Chest Physicians 2004 guidelines) and with no contraindications for anticoagulation. Inpatient anticoagulant groups were assigned based on the drug the patient received during hospital stay and were followed by their outpatient prophylaxis use. Patients were evaluated on drug utilization, diagnoses and clinical practice patterns during and after hospitalization. Results: Overall, 75.3% of 2,337 cancer patients did not receive anticoagulation during their hospital stay. Of the 577 patients receiving prophylaxis, 66% received UFH and 25% received enoxaparin ( Table ). The mean length of hospital stay was 3 days after which 97.9% of patients did not receive any prophylaxis within the following 30 days. Of the 50 patients who received outpatient prophylaxis, 60% received warfarin alone and 22% received both enoxaparin and warfarin. Conclusions: This unique analysis presents VTE prophylaxis patterns across the continuum of care. Most cancer patients did not receive anticoagulation in the inpatient or outpatient settings. Further efforts are needed to identify optimal VTE prevention in cancer patients, namely the duration of prophylaxis and how healthcare providers can increase awareness. Financial and editorial support was provided by sanofi-aventis US, Inc.

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Systematic review of research trends in cancer cachexia: Insights from the literature and funding agencies
Authors: Braiteh F. S. , Pratt G. , Kurzrock R. , Bruera E.
Published: August 2020

e17540

Background: Cancer cachexia affects about 250,000 patients in the US worsening treatment outcome and quality of life. To evaluate the scholar contribution to cancer cachexia, we analyzed the cachexia literature and funding support. Methods: In May 2008, we conducted a search of the major databases Medline, Web of Sciences, and Scopus of all publications with MeSH heading “cachexia” or keywords “cachexia, cachectic, cachexic” since 1982, distinguishing “original research” from “review” articles. To examine the trend over time, we compared the publication rate in the field of cachexia to that of published manuscripts in reference fields (cancer, AIDS, Alzheimer's disease, and CHF). To study the federal funding for cachexia research, we examined the Computer Retrieval of Information on Scientific Projects database. Only descriptive statistical analysis was adopted because of the heterogeneity of methods. Results: We identified 1990 published manuscripts, 677 (34%) of which are “reviews”. Out of the 2,890 country of origin affiliations, the US is the lead contributor (N = 1,105; 38%). In the last 5 years, the ratio of “review” articles in cachexia increased significantly (49%), compared to cancer (17%), and science publications (8%). Unlike the of publications in reference fields, the increase in cachexia has been mostly due to the dominance of “review” articles (ratio of original/review of 0.928 in cachexia, versus 0.417 in CHF, 0.337 in Alzheimer and 0.206 in AIDS). Nevertheless, published cachexia articles in journals with high impact factors (IF ≥ 4.0) remains similar (8.49%) to that of science research (8.63%) with a predominance of “review’ articles. Only one in four published manuscripts (24%) acknowledged federal support. Cachexia research support by US federal agencies declined significantly in the last decade (with a peak of 161 awards in 1999 down to 40 in 2006), the NCI remains the leading funding agency (17%). Only 275 out of the total of 121,997 NCI- awards over 25 years (0.22%) were awarded to cachexia research, with a clear decline in the latest decade by 50% (0.14% vs. 0.29%). Conclusions: Advances in the field of original cancer cachexia research have been very limited, perhaps related to the lack of federal research funding support, which is on the decline.

No significant financial relationships to disclose.
Use of growth factors associated with docetaxel and paclitaxel in patients with early-stage breast cancer in a community oncology center
Authors: Boklage S. H. , Chen L. , Christiansen N. P. , Sullivan S. D. , Hay J. W. , Mullins C. D.
Published: August 2020

e17548

Background: Docetaxel and paclitaxel are widely used in treating breast cancer (BC), and both have hematologic toxicity commonly managed by costly growth factors (GFs). However, the extent of GFs use in real-world clinical practice has not been well documented. Methods: The Georgia Oncology Specialist Database was used and contained chemotherapy, medical and pharmacy claims, and lab results for nearly 170,000 patients with various types of cancer (2003–2008). Patients with stage I-III BC receiving docetaxel- or paclitaxel-containing regimens as adjuvant therapy were followed from 1 week prior to docetaxel or paclitaxel (index drug) initiation to the earliest of death, loss to follow-up, switch in taxane, or end of 90-day period post last dose of index drug. Incidence of GFs use per person-year was compared using univariate negative binomial (NB) model, median time to first GFs use was compared using Wilcoxon test. Multivariate analyses were performed on number of utilizations and time to first utilization adjusting for potential confounders. Results: Compared with paclitaxel (n = 433), docetaxel cohort (n = 216) had lower incidence per person-year of erythroid stimulating agents (ESAs) use (8.01 vs. 11.72, p = 0.008), while similar incidence of myeloid growth factors (MGFs) use (8.51 vs. 5.07, p = 0.541). Lower MGFs utilization in docetaxel patients (ratio of number of utilization = 0.821, p = 0.033), and similar ESAs utilization (ratio of number of utilization = 0.920, p = 0.305) were found. While descriptive analysis showed paclitaxel patients received first ESAs sooner than docetaxel patients (median length: 23 vs. 7 days, p < 0.001), and no difference in time to first MGFs use (median 8 days for both); multivariate analyses found docetaxel patients received first MGFs sooner (ratio of days = 0.828, p = 0.039), and no difference in time to first ESAs use (ratio of days = 1.091, p = 0.419). Conclusions: This analysis suggests that docetaxel is associated with lower utilization of MGFs. Studies examining the economic impact of GFs use associated with taxanes will need to be conducted. A potential limitation of this study is that the potential selection bias may not be fully adjusted.

[Table: see text]
Sniffing out cancer from real breath samples by means of nanomaterial-based electronic nose device
Authors: Abdah-Bortnyak R. V. , Haick H. , Billan S. , Peng G. , Trock E. , Shachada N. , Kuten A.
Published: August 2020

e17552

Background: Several studies have shown that characteristic patterns of volatile organic compounds (VOCs) appear to be elevated in the alveolar breath of cancer patients, as compared to healthy controls. It has been shown, that VOCs’ composition acts as a fingerprint for the distinction of a certain cancer from other cancers, including the cases where various cancers have similar type of biomarkers. The goal of the current study is to establish a background to ultimately achieve a simple-to-use device that can detect such patterns of cancer when exhaling into it. Methods: Breath samples were collected from 40 healthy volunteers and 75 patients having known conditions in six main categories: (I) 40 healthy controls; (II) 30 patients with lung cancer; (III) 15 patients with breast cancer; (IV) 20 patients with colon cancer; (V) 5 patients with prostate cancer; and (VI) 5 patients with head and neck cancer. The breath of the volunteers was examined by means of gas chromatography linked with mass spectrometry technique (GC-MS) as well as by an electronic nose device that is based on molecularly modified Au nanoparticles to check the feasibility of the electronic nose in cancer detection via breath samples Results: GC-MS results showed that each category of cancer has a unique pattern (or mixture) of VOCs. In parallel to these findings, results indicate the ability of nanomaterial-based electronic nose devices to differentiate between “healthy” and “cancerous” breath, and, furthermore, between the breath of patients with different cancer types, with >92% sensitivity. Conclusions: The electronic nose technology has a high potential for assessing various types of cancer via simple exhalation procedure. The results provide a launching pad towards obtaining an inexpensive, compact tool that is amenable to widespread screening and that has a potential for direct and real-time monitoring (2–3 minutes only).

No significant financial relationships to disclose.