bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ki67 expression as a predictor for suboptimally debulked patients with advanced epithelial ovarian cancer
Authors: Adams S. F. , Levine D. A. , Zhang L. , Barakat R. , Boyd J. , Gimotty P. , Coukos G. 
Published: March 2020

5563 Objective: The death rate from ovarian cancer has not changed significantly in several decades. Additional prognostic biomarkers may allow for more tailored chemotherapy and an improved response rate. Our aim was to clarify the utility of Ki67, a nuclear protein expressed by mitotic cells, as a prognostic marker in cases of advanced epithelial ovarian cancer (EOC). Methods: We conducted a retrospective cohort study of patients undergoing primary surgery for advanced EOC between 1989 and 2003 at one institution. All were diagnosed with serous or poorly differentiated ovarian adenocarcinoma, and received platinum/paclitaxel chemotherapy. Snap-frozen surgical specimens were subjected to immunohistochemical analysis using a monoclonal antibody against human Ki67. Cases were stratified into those wtih high (>25%) or low expression (<25%) of Ki67 based on the percentage of postively-staining tumor cells. Kaplan-Meier curves were used to estimate five-year survival rates, and were compared using a log-rank statistic. Results: 134 cases (106 stage III; 28 stage IV) were analyzed. Average age at diagnosis was 62 (range 26–84 years); average duration of follow-up was 42 months (range 0.7 - 128.8). 61 (45%) patients were optimally debulked. The 5-year survival rates were 24.7% and 41.4% (p=0.0421) for patients with high and low Ki67 expression, respectively. Patients in these two groups did not differ significantly with regard to age, tumor grade, debulking status, histotype, or stage. Sub-group analysis indicated that the differential effect of Ki67 expression existed exclusively among patients who were suboptimally debulked, with a 5-year survival of 16% vs. 39% (p=0.027) for cases with high vs. low Ki67 expression. There was no difference in survival among optimally debulked patients based on Ki67 expression (43% vs. 48%, p=0.890). Conclusion: Ki67 immunostaining provides robust prognostic information for patients with advanced EOC who are incompletely debulked at primary surgery. This biomarker may define subgroups of patients who would be more likely to benefit from cell-cycle dependent chemotherapy regimens, and may guide the development of future therapeutic strategies. No significant financial relationships to disclose.
Mature results of a phase II study of intraperitoneal topotecan as consolidation therapy in ovarian cancer
Authors: Malpass T. W. , McGonigle K. , Roberston M. , Weiden P. , Muntz H. G. 
Published: March 2020

5570 Background: Previous studies with intraperitoneal (IP) topotecan have shown 20 mg/m2 to be well tolerated. This study evaluated the feasibility, safety, and effectiveness of IP topotecan as consolidation therapy for ovarian cancer. Methods: Patients with stage III/IV ovarian (or primary peritoneal) cancer in clinical complete response after cytoreduction and IV chemotherapy with carboplatin and paclitaxel who had benign findings or minimal persistent disease (<= 1 cm diameter) documented at second-look surgery were eligible. IP topotecan 20 mg/m2 was administered once every 21 days for 4 to 6 cycles. Dose reduction was based on grade 3–4 toxicities. Hematopoietic growth factors were used at the discretion of the treating physician. Results: Twenty patients were enrolled (18 ovarian and 2 peritoneal cancers). Sixteen patients received 4 cycles, 3 patients received 6 cycles, and 1 patient withdrew by personal request after 1 cycle. Of the total 83 cycles, 10 (12%) were delayed due to slow recovery of neutropenia, and 22 (27%) were administered with does reductions due to prior grade 3–4 myelosuppression. Mean delivered dose was 18 mg/m2. Major toxicities included episodes of neutropenia (6 grade 3; 3 grade 4) and thrombocytopenia (7 grade 3; 2 grade 4). Filgrastim was administered to 75% of patients in 51 (61%) cycles, and epoetin alfa was administered to 30% of patients in 20 (24%) cycles. Other adverse events (grade 1 or 2) that occurred in approximately half of patients included nausea and abdominal distension. Median progression-free survival was 24 months from second-look surgery (Kaplan-Meier, 95% CI 14–34 months). Sixteen patients (80%) are alive after median of 42 months from second look surgery (range, 29 to 62 months), with 4.5 year estimated overall survival of 84% (95% CI 68–100%) measured from original diagnosis. Conclusion: Consolidation IP topotecan 20 mg/m2 every 3 weeks for 4–6 cycles is feasible and well tolerated. Progression-free and overall survival in this pilot study compare favorably with results expected for advanced ovarian cancer. Future investigation of IP topotecan is warranted, both as consolidation therapy and salvage therapy for advanced ovarian cancer. No significant financial relationships to disclose.
Influence of sequencing of chemotherapy and radiotherapy regarding adverse effects of the cytostatic treatment: Results of the ADEBAR trial
Authors: Sommer H. L. , Jueckstock J. K. , Genss E. , Annecke K. , Rack B. , Steinfeld-Birg D. , Harbeck N. , Kiechle-Bahat M. , Janni W. J. , Friese K. 
Published: March 2020

559 Background: The ADEBAR-trial was designed as a multicenter randomised phase III study for high risk primary breast cancer (BC) pts., i.e. with more than 3 axillary lymph node metastases. Primary objective of the trial was to evaluate the benefit of a sequential anthracycline-docetaxel regimen (E90C-D: 4 cycles epirubicin [E] 90 mg/m2 plus cyclophosphamide [C] 600 mg/m2 q21 days followed by 4 cycles docetaxel [D] 100mg/m2 q21 days) compared to dose-intensive anthracycline- containing polychemotherapy (FE120C: 6 cycles E 60 mg/m2 d 1+8, 5-FU 500mg/m2 d 1+8 and C 75 mg/m2 d 1–14, q4 weeks). Patients and Methods: The study started in 2001 and was closed in 2005. By this time 200 actively participating sites had recruited a total number of 1,502 patients. One of the stratification issues was the sequencing of chemotherapy and radiotherapy. All patients were required to receive adjuvant radiotherapy. However the timing of irradiation, either in a sandwich setting after the first half of chemotherapy cycles or after completion of the entire cytostatic treatment was at the discretion of the study sites. In a toxicity-analysis in December 2006, the influence of sequencing of chemotherapy and radiotherapy was analyzed in 980 patients. Results: In 223 pts. radiotherapy was performed midtime after the first half of chemotherapy cycles, 757 pts. received radiotherapy only after completing the entire cytostatic treatment and before starting endocrine treatment, if applicable. Hospitalisation occurred in 32.7 % (73 pts.) of the sandwich group and in 27.9% (211 pts.) of the sequential group (p-value = 0.160). Interval prolongation was necessary in 37.7% (84 pts.) versus 31.6% (239 pts.) in the sequential group, (p-value = 0.089). The target dose was reduced in 15.7% (35 pts.) in the sandwich group and in 20.2% (153 pts.) of the sequential group, (p-value = 0.132). SAEs occurred in 29.6% (66 pts.) in the sandwich group versus 23.1% (175 pts.), (p-value = 0.048). Conclusion: No consistent association between treatment toxicity and the timing of chemotherapy and radiotherapy was observed. Because in this high risk patient group, the prevention of systemic relapse is most important, chemotherapy should be completed before the start of radiotherapy. No significant financial relationships to disclose.
A phase II trial of the use of 4,4’-dihydroxybenzophenone-2,4-dinitrophenyl-hydrazone (A-007) topical gel in the treatment of high-grade squamous intraepithelial lesions (HSIL) of the cervix
Authors: Muñoz D. , Cantu D. , Gonzalez A. , Meneses A. , Mohar A. , Astudillo-de la Vega H. , Nguyen B. 
Published: March 2020

5593 Background: The incidence of cervical cancer is highly correlated with cervical high grade squamous intraepithelial lesions (HSIL [CIN2/3]) and human papillomavirus (HPV) infection in men and women. Approximately 70 - 80% of sexually active adolescents and adults will become infected with HPV during their lifetime. In 2003 alone, there were 50 million cases of HPV infections in the United States. Our main objective is to determine the pathological response (complete and partial, based on independent review panel of two patho the uterine cervix of women with HSIL [CIN 2/3]. Materials and Methods: Following colposcopy, pap smear and biopsy confirmation of HSIL (CIN 2/3) and HPV infection status, women are treated with gel applied to the cervix via an intravaginal applicator once daily for 5 consecutive days of a 28-day cycle for 2 cycles. At month 4 post enrollment into the trial, all women undergo the loop electrosurgical excision procedure (LEEP) procedure and repeated virology assessment. Results: 65 patients were enrolled at 2 centers and completed treatment with A-007 and 100% (65/65) were HPV positive (81.5% by Hibrid Capture II for High Risk and 100% PCR positive). All baseline and LEEP pathological specimens will be blinded read by a panel of two independent expert pathologists. A subject will be considered a complete pathological responder (CR) when the patient has regression of HSIL (CIN 2/3) without pathological evidence of HSIL, and a partial pathological responder (PR) when she has regression of HSIL (CIN 2/3) to LSIL (CIN 1). Overall response rate is defined as the percentage of patients with CR and PR. To date, no serious adverse events (SAE) has been reported during treatment in all enrolled patients, only has been reported a moderate local and transitory itching/burning sensation during the first 5–20 minutes after application in 18% (12/65) of the cases. At this moment LEEP procedures are being scheduled for all patients and the pathological response rate as well as the HPV response rate will be available and presented at the conference. [Table: see text]
Retrospective analysis of two modes of lymphadenectomy (para-aortic + pelvic vs. pelvic alone) with regard to survival in endometrial cancer: A comparative study of two gynecologic units
Authors: Handa Y. , Kato H. , Hareyama H. , Hada K. , Kaneuchi M. , Oikawa M. , Mitamura T. , Aono A. , Saitoh Y. , Okuyama K. , Yamashita K. 
Published: March 2020

5599 Background: Patients with endometrial cancer are at high risk of severe post-operative complications because of obesity, diabetes mellitus, and hypertension. The purpose of this study is, for minimizing surgical injury, to determine whether para-aortic lymph nodes dissection is dispensable. Methods: 295 patients received hysterectomy and lymphadenectomy during 1995 - 2005 in two gynecologic units of hospitals, one of where para-aortic lymph nodes (to the level of renal vein) and pelvic lymph node (PAN+PLN) dissection were routinely performed and the other only pelvic lymph node (PLN) were dissected, were enrolled. Their overall survival was retrospectively compared between these units. Results: Mean lymph node count was 58.9±19.7 in 99 patients with PAN+PLN lymphadenectomy, and 36.8±14.6 in 196 patients with PLN alone. 5-year survival was 93.3% in PAN+PLN cases and 92.9% in PLN, with no significant difference. Cases who died of the disease (DD) were 6.1% in PAN+PLN and 9.2% in PLN (relative risk = 0.660). Distribution in each stage was ignorable between two units; however, specific histology types, such as serous, clear cell, and carcinosarcoma, were highly counted in DD of the PLN unit. 5-year survival of only endometrioid type, excluding specific histology types, was 92.9% in PAN+PLN and 95.1% in PLN, and DD were 6.6% in PAN+PLN and 6.0% in PLN (RR = 1.095). Lymph node metastases were found 13.1% in PAN+PLN and 4.1% in PLN. One case was observed PAN-alone metastsis, where histology was serous type. Conclusions: Overall survival in patients received PAN+PLN and PLN dissection is not significantly different in endometrial cancer. It is supposed that only PLN dissection is sufficient and PAN dissection is omittable especially in endometrioid type, however, PAN+PLN lymphadenectomy might be suggestive to reduce death in specific histology types. No significant financial relationships to disclose.
Are BRCA1 mutations a predictive factor for anthracycline-based neoadjuvant chemotherapy response in triple-negative breast cancers?
Authors: Petit T. , Wilt M. , Rodier J. , Muller D. , Ghnassia J. , Dufour P. , Fricker J. 
Published: March 2020

580 Background: BRCA1 being involved in DNA repair and apoptosis, its mutations may influence response to chemotherapy. In vitro studies demonstrated that loss of BRCA1 function increased sensitivity to platinum compounds and induced resistance to anthracyclines. BRCA1-related breast cancers tend to be ductal carcinomas with high tumor grade, absence of hormonal receptors and no HER2 overexpression, so called triple-negative. We retrospectively analyzed anthracycline-based neoadjuvant chemotherapy efficacy in triple- negative tumors according to BRCA1 status. Methods: 393 breast cancer pts were treated with FEC100 neoadjuvant chemotherapy (FU 500 mg/m2, epirubicine 100 mg/m2, cyclophosphamide 500 mg/m2) between 1/2000 and 12/2006. Out of them, 14% had a triple-negative phenotype (55 pts). Patients with young age at diagnosis or family history of breast cancer were offered genetic testing for BRCA1 and BRCA2 mutations. Twelve of these patients had a BRCA1 deleterious mutation with a triple-negative tumor. Characteristics of these 12 pts at diagnosis were: median age = 38, tumor stage = 7 T2N0, 2 T2N1, 2 T3N0, 1 T3N1. Results: Pathological complete response was defined as absence of invasive tumor in breast and axillary nodes. After 6 cycles of FEC100, 42% of patients with triple-negative tumors (23/55) had a pathological complete response, compared to 17% (2/12) with a BRCA1 mutation. Only one of the 12 BRCA1 patients had an axillary node involvement. Conclusions: In our series, BRCA1 deleterious mutations decreased anthracycline-based chemotherapy efficacy in triple- negative breast cancers. Platinum compounds should be evaluated in these BRCA1-related tumors. No significant financial relationships to disclose.
The ADEBAR trial: Final toxicity analysis of a phase III study evaluating the role of docetaxel in the adjuvant therapy of breast cancer patients with extensive lymph node involvement
Authors: Janni J. W. , Sommer H. , Rack B. , Augustin D. , Simon W. , Steinfeld D. , Annecke K. , Harbeck N. , Friese K. , Kiechle-Bahat M. 
Published: March 2020

585 Background: Taxane based adjuvant chemotherapy has been established as standard treatment in node-positive breast cancer. However, toxicity concerns of combined anthracycline-taxane regimens have compromised its acceptance. We analyzed the toxicity of a sequential anthracycline-taxane chemotherapy compared to a conventional anthracycline regimen. Patients and Methods: ADEBAR was a multicenter phase III trial (n=1,502) to evaluate whether breast cancer (BC) pts with > 3 axillary lymph metastases benefit from a sequential anthracycline-docetaxel regimen (E90C-D: 4 cycles epirubicin [E] 90 mg/m2 plus cyclophosphamide [C] 600 mg/m2 q21 days followed by 4 cycles docetaxel [D] 100mg/m2 q21 days) compared to dose-intensive anthracycline-containing polychemotherapy (FE120C: 6 cycles E 60 mg/m2 d 1+8, 5-FU 500mg/m2 d 1+8 and C 75 mg/m2 d 1–14, q4 weeks). We present the final toxicity analysis. Results: Complete toxicity data were available from 1,338 pts. Treatment was stopped prematurely in 3.7% of the pts in the E90C-D arm and in 8.0% in the FE120C arm due to toxicity (p=0.0009). Antibiotic treatment was given in 10.4% (E90C-D) vs. 19.7% (FE120C), G-CSF support in 39.2% vs 61.4 % and erythropoietin stimulation in 8.7% vs. 20.0%, respectively (p<0.0001). Hematologic and non-hematological grade 3–4 toxicities are summarized in the table . In summary, haematological toxicity (leucopenia, infection thrombocytopenia, anemia) was significantly greater in the FE120C-arm. Skin toxicity, edema and vomiting occurred significantly more often in pts treated with E90C-D. Conclusion: Different toxicity profiles given, overall toxicity of a sequential anthracycline-taxane regimen is not necessarily greater than that of an adequately dosed anthracycline chemotherapy, which needed to be interrupted more frequently due to toxicity. [Table: see text] No significant financial relationships to disclose.
BCCIP: A novel marker for radiotherapy benefit in patients with laryngeal cancer
Authors: Rewari A. , Lu H. , Yang Q. , Shen Z. , Haffty B. 
Published: March 2020

6006 Background: It has been well established that the functionality of the p53 pathway is related to radiosensitivity in various human cancers. The status of proteins regulating p53 activity may also be valuable markers for radiosensitivity. Recent studies have shown that BCCIP (BRCA2 & CDKN1A interacting protein) is essential for maintaining the transactivation activity of wild type p53. We hypothesize that functional BCCIP may contribute to effective radiotherapy in the clinical setting. To test this hypothesis, we analyzed the expression of BCCIP and p53 in a cohort of laryngeal cancer treated with radiotherapy and assessed whether BCCIP and p53, alone or in combination, would correlate with local control and overall survival. Methods: One hundred thirty-five patients treated between 1975 and 2000 for early stage (stage I & II) squamous cell carcinoma of the larynx were included in the study. Treatment consisted of definitive radiation therapy (RT) with standard fields and fractionation to a median dose of 6,590 cGY. Tissue was collected from pre-RT biopsies and constructed in a tissue microarray, with duplicate cores created for each case. BCCIP and p53 expression was analyzed by immunohistochemistry and qualitatively scored with greater than 10% nuclear reactivity the cutoff for positive staining. Results: Expression of BCCIP and wild type p53 in combination was associated with significant improvements in 5-year local control (68.75% vs. 46.27%, p = .04) and 5-year overall survival (67.68% vs. 34.62%, p = .006) compared to patients who did not express BCCIP. Expression of BCCIP or p53 alone was not found to be independently associated with benefits in local control or overall survival. Conclusions: This study provides clinical evidence that BCCIP contributes to effective local control and overall survival in patients with laryngeal cancer treated with radiation. This benefit may be a result of increased radiosensitivity in patients who have functional BCCIP and p53. Using immunohistochemical methods, BCCIP and p53 co-expression can act as markers to identify sub-groups of laryngeal cancer patients who are more likely to be cured with radiotherapy. No significant financial relationships to disclose.
Phase II evaluation of cetuximab (C225) combined with induction paclitaxel and carboplatin followed by C225, paclitaxel, carboplatin, and radiation for stage III/IV operable squamous cancer of the head and neck (ECOG, E2303)
Authors: Wanebo H. J. , Ghebremichael M. , Burtness B. , Spencer S. , Ridge J. , Forastiere A. , Ghebremichael M. 
Published: March 2020

6015 Introduction: Neoadjuvant C225 with induction chemotherapy and chemo-radiation was studied in stage III/IV head and neck squamous cancer with primary and secondary objectives of 1year event- free survival, pathologic complete response rate at the primary site (PS) (determined by mandatory biopsy week 8) and toxicity. Protocol Design: Operable patients (pts) staged by triple endoscopy, CT/MRI, had gastrostomy, signed IRB approved consent and received induction chemotherapy with weekly C225 250 mg/m2, P 90 mg/m2, C (AUC=2). Restaging PS biopsy was done at week 8, if there was a clinical response. Pts with positive biopsy (or persistent tumor) at PS had restaging biopsy at week 14 after chemo radiation (C225 250 mg/m2, P 30 mg/m2, C(AUC=1) and 50 Gy). If PS Bx was negative patients had completion RT (68–72 Gy, plus continued C225, P,C). If PS Bx was positive at 14 weeks salvage surgery was required. Results: 74 patients were enrolled (67 are evaluable). T and N stage were T1/2 (11%/27%), T ¾ (47%/14%); N O/N1 (11%/23 %), N 2/3 (50%/16%). Site: tonsil 30%, oral cavity/tongue 24%, Post pharynx (BOT) 42%, Larynx 34%; performance status 0/1 (61% / 39%). PS re biopsy was done at week 8 in 40 patients; no residual tumor was detected in 26 (65%). Restaging biopsy after induction and chemo radiation was done at week 14 in 28 pts (14 with persistent tumor and 14 with previous positive biopsy) and was negative in all 28 patients. All 54 patients with negative PS biopsy had completion RT. Data on disease status are incomplete. Post treatment toxicity (Gr 3/4) included acneiform rash (12%), leukopenia/neutropenia 32%/24%, dysphagia (29%), and stomatitis (82%). One grade 5 AE occurred (death from encephalopathy). Conclusion: Neoadjuvant induction C225, plus chemotherapy followed by C225 plus chemo-radiation elicited a complete pathologic response at the primary site, by restaging biopsy (65%) with induction alone, and 100% among sampled patients after chemo RT 50Gy. These preliminary results suggest a high pathologic complete response rate to induction chemotherapy plus cetuximab followed by chemo radiation plus cetuximab. Progression and survival data are not yet mature. No significant financial relationships to disclose.
Gene copy number of epidermal growth factor receptor (EGFR) by fluorescent in situ hybridization (FISH) in head and neck squamous cell carcinomas (HNSCC) is closely correlated with EGFR protein levels assessed by automated quantitative protein analysis (AQUA)
Authors: Weinberger P. , Psyrri A. , Kountourakis P. , Rampias T. , Sasaki C. , Sasaki C. , Haffty B. , Kowalski D. , Fountzilas G. , Rimm D. , Burtness B. 
Published: March 2020

6023 Background: EGFR overexpression correlates with recurrence and with treatment resistance in HNSCC. The mechanisms of EGFR protein overexpression are poorly understood. Nonetheless, previous investigators have not demonstrated a correlation between EGFR gene copy number and protein content, using conventional immunohistochemistry (IHC). The aim of this study was to evaluate the relationship of EGFR gene copy number and protein expression utilizing fluorescence in situ hybridization (FISH) and AQUA, a novel, immunohistochemical method of automated quantitative in situ proteomic analysis which permits subcellular localization. Methods: A tissue microarray composed of 137 HNSCC treated with (chemo)radiation was constructed and analyzed for EGFR copy number by FISH (Vysis/Abbot) and EGFR protein expression (DAKO antibody) using AQUA analysis of EGFR staining scored on a scale of 0–255 and by conventional IHC. Agreement was assessed using kappa. Results: Sixteen (15%) of one-hundred six tumors with FISH results demonstrated EGFR high polysomy and/or gene amplification (FISH+). AQUA demonstrated a range of 3.6–102.2; protein levels assessed by AQUA in the FISH amplified cases were significantly higher (p =0.008) than in the FISH non- amplified ones. Using the EGFR 75th percentile as a cut-off, AQUA and FISH showed significant agreement (percentage of overall agreement 82%, kappa=0.458, p=0.003). To the contrary there was no concordance between FISH and conventional IHC results in this series. Conclusions: The discrepancy between EGFR gene amplification rate and protein expression by IHC reported previously may be due to the limitations and nonquantitative nature of conventional IHC. EGFR protein content correlates with gene copy number if protein content is quantitated and automatically analyzed, as with AQUA. No significant financial relationships to disclose.