bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pharmacogenetic UGT1A1 dose-escalation study for recurrent and refractory gynecologic cancer patients treated with combination therapy of irinotecan and cisplatin
Authors: Takano M. , Kato M. , Yoshikawa T. , Hirata J. , Takahashi M. , Yokota H. , Kino N. , Goto T. , Konno R. , Fujiwara H. 
Published: August 2020

e16536 Background: In addition to polymorphisms of UGT1A1*28, UGT1A1*6 has been recognized as a risk factor for severe irinotecal-related toxicities. We have conducted an UGT1A1 genotype-based dose-escalation study for recurrent and refractory gynecologic cancer patients (pts) treated with combination with irinotecan and cisplatin (CPT-P). Methods: Pts eligible for this study had histologically confirmed uterine cancer or ovarian cancer, who received CPT-P; a course of therapy consisting of 40–80 mg/m2 of irinotecan on days 1, 8, and 15 and 60 mg/m2 of cisplatin on day 1, q4weeks. Polymorphisms of UGT1A1*28 and *6 were analyzed and the pts were categorized into three groups (wild-type, hetoro-type, and homo-type). Pharmacokinetics of CPT-11, SN-38, SN-38 glucuronide (SN-38G), and platinums were analyzed according to the UGT1A1 genotyping. Results: During August 2008 and December 2008, 17 pts were enrolled in this study; 12 ovarian cancers and 5 uterine cancers. Genotypes of UGT1A1 were wild in 9 pts (53%), *28 in 4 pts (24%), *6 in 3 pts (18%), *6/*6 in 1 pt (6%). At the starting doses of irinotecan (60 mg/m2 for wild-type and 40 mg/m2 for hetero-/homo-type), dose limiting toxicities were observed in two of six wild-type cases and one of six hetero-type cases. Pharmacokinetic analyses revealed hetero-type cases were associated with lower area under time-concentartion curve (AUC) SN-38G to SN-38 (AUCSN-38G/AUCSN-38) compared with wild-type cases (p = 0.02), however, there was no significant difference of AUCSN-38at the starting dose. Additionally, AUC of platinum was slightly higher in hetero-type cases in comparison with wild-type cases (p = 0.04). Pharmacokinetics of the drugs were similar between *28 and *6 cases. Conclusions: The present study indicated clinical significance of UGT1A1 genotyping upon pharmcokinetics of not only SN-38G/SN-38 but also platinum. In addition to UGT1A1*28, UGT1A1*6 was a key candidate to influence the pharmacokinetics of CPT-P regimen in gynecologic cancer patients. No significant financial relationships to disclose.
Clinical outcome in patients with endometrial papillary serous and endometrioid carcinomas as related to WT-1, Pax-2, and p16 immunohistochemical expression profiles
Authors: Rollins-Raval M. , Byler Dann R. , Edwards R. P. , Chivukula M. 
Published: August 2020

e16547 Background: Endometrial papillary serous carcinoma (EPS) can be difficult to differentiate histologically from high grade endometrial endometrioid carcinoma (EE). Both of these tumors often present with solid growth pattern with few papillary features. Recurrences have been found to be more frequent in EPS than high grade EE. These differences were found despite the same preoperative and postoperative radiotherapy and chemotherapy, indicating more aggressive tumor biology. To date, there are no well defined immunophenotypic or molecular methods to differentiate these two tumors or their clinical behavior. Methods: Eleven cases of EE and twenty-three cases of EPS were retrieved from our departmental archives and stained using Pax-2, WT-1 and p16 antibodies. For all three antibodies, a strong nuclear staining is considered positive. The intensity and proportion of cells positive are noted. Seven cases from each group were further examined for their staging and clinical outcome in terms of recurrence, metastasis and treatment. Results: WT-1 is negative in 100% of EE cases. p16 is positive in 95% of EPS cases, and only 55% of EE cases. In addition, out of the seven EPS patients whose clinical information was obtained, the three EPS patients who had strong Pax-2 staining are still alive more than two years status post surgical intervention, while four other EPS patients are deceased. The three patients with the strongly staining PAX-2 EPS tumors all had varying tumor characteristics, recurrence and adjuvant therapies. This finding is now being evaluated in the additional cases. Conclusions: WT-1, Pax-2 and p16 are useful to differentiate high grade EE and EPS cases. Strong Pax-2 staining in three cases of EPS with better outcome is an interesting finding that deserves further investigation. No significant financial relationships to disclose.
Experience with endometrial carcinoma (EC): A population-based study in Tarragona Province (Spain)
Authors: Arenas Prat M. , Rovirosa A. , Sabater S. , Ameijide A. , Henríquez I. , Servitja S. , Cabezas I. , Mur E. , Gumà J. 
Published: August 2020

e16550 Background: To evaluate outcome, failure patterns, prognostic factors and radiotherapy (RT) toxicity after postoperative RT for EC in Tarragona Province (Spain). Methods: A retrospective population-based review on 232 patients (pts) between 1997 and 2000 from different gynaecological Dpt. and in a single oncologist institution with RT Units. Multivariate analysis of disease-free survival (DFS), overall survival (OS), adjuvant RT, RT toxicity (RTOG), prognostic factors for survival, and the distance in Km to the RT Units. Results: Mean age: 64 years (35–88). Distance to RT Units >70 Km in 15% pts. Median follow-up: 70 months (2–132). FIGO Stage (S): 8.2% IA; 36.2% IB; 19% IC; 7.8% IIA; 6.5% IIB; 7.3% IIIA; 1.3% IIIB; 3.4% IIIC; 2.6% IVA; 2.2 IVB. Pathology: endometrioid 74.5%, papillary 3.9%, serous 3.4%, clear-cell 2.2%, squamous cell 3%, adenosquamous 1.3%, mixed 3.9%. Grade (G): 35.7% G1, 45.3% G2, 19% G3; miometrial invasion: 44.1% >50%, 46% <50%, 9.9% not invasion. Treatment: 1) Surgery in 93.5%, 49.6% lymph nodes dissection. 2) RT in 73.5%: 47% external beam radiotherapy (EBI) and brachytherapy (BT), 9.4% BT alone, 17.1% EBI alone. 3) Chemotherapy in 11.1% and hormonal treatment in 6.9%. 3). Grade 3 and 4 toxicity: 12 (9%) pts, 6 early and 6 late. Relapses: 26/232 (11.6%), S-I: 11/26 (42%), S-II: 1/26 (3.8%), S-III: 5/26 (19.2%), S-IV: 3/26 (11.5%). Metastasis: 28/232 (12.5%). Survivals at 5 years: 1) OS in all stages was 78.8% and 83%, 89.6%, and 76% for SI, SII, and SIII, respectively. 2) DFS was 76.5% for all pts and 82.3%, 86.22%, and 68.24% for SI, SII, and SIII, respectively. Multivariate analysis: significant prognostic factors for poor outcome were age (p < 0.01), lymph nodes dissection (p < 0.001), pathologic subtype (p < 0.001), grade of differentiation (p < 0.001), and deep myometrial invasion (p < 0.005). Conclusions: Survivals, RT toxicity and relapse sites were similar to the other reported series. Predictors of poor outcome were age, lymph nodes dissection, pathology subtype, grade of differentiation, and deep myometrial invasion. Patients of Tarragona Province are in need of a better accessibility to the radiation units. No significant financial relationships to disclose.
Phase II trial of imatinib mesylate (I) in combination with docetaxel (D) in the treatment of patients (pts) with recurrent or persistent epithelial ovarian carcinoma (EOC)
Authors: Usha L. , Larson M. L. , Kazmi N. , O'Brien T. , Winkelman L. A. , Rotmensch J. 
Published: August 2020

e16552 Background: D has a known single-agent activity in advanced EOC with the response rate of at least 10%. I is a multi-targeted tyrosine kinase inhibitor shown in preclinical studies to decrease interstitial pressure in the tumor and facilitate influx of chemotherapeutic agents into the tumor. Methods: A single-institution trial was conducted in pts with advanced EOC in 2005–2007. The primary endpoint of the study was to determine a tumor response to the study combination. Pts were required to have received 1 or 2 prior chemotherapeutic regimens including a platinum compound and have performance status 0–2. Pts were to receive D 60 mg/m2 IV every 3 weeks and I 400 mg/day by mouth continuously. Planned target accrual for the first stage of the study was 15 pts with the preset minimum of 3 responses to proceed to the second stage. Tumor response was evaluated by RECIST criteria after every 3 cycles of D. Treatment was continued until disease progression or unacceptable toxicity. Results: Study was terminated early due to lack of response and significant toxicities. A total of 10 pts were enrolled. The age range of the pts was 55–79 with the mean age = 64. Five pts were evaluable for response and in all of them, cancer progression was observed after 3 cycles of combination therapy (0 responses). Five pts were taken off the study after 1 cycle of treatment either due to serious adverse events (SAEs) or disease progression. Among grade 3 and 4 SAE's observed in the study were 4 cases of hematological toxicity, 1 case of rash, 1 case of dizziness, and 1 case of deep venous thrombosis. The median progression-free survival for pts on the study was 7.5 weeks. Conclusions: Although the sample size of this study was small, the combination of I and D at the above doses appears ineffective in the population of moderately-pretreated women with advanced EOC. The majority of grade 3 and 4 SAE's were due to myelosuppression likely caused by D rather than I. No significant financial relationships to disclose.
The expression and clinical significance of clusterin and ki67 in cervical cancer
Authors: Shrestha E. 
Published: August 2020

e16554 Background: To explore the expression pattern and clinical significance of the CLU and proliferation indices ki67 in cervical cancer. Methods: 59 cases treated at Cancer Center Sun Yat-sen University during 1989–2006 were enrolled in the study group. The relationship was analyzed for the expressions of CLU and Ki67 with clinical factors. Results: In this study positivity of CLU in cervical SCC, 10% (3/31) cases weak positive, adenocarcinoma 21% (4/19) weak positive in small cell carcinoma 11% (1/9) moderate positive. Control groups, CLU weak positive expression, 21% (3/14) CIN 2–3 and 14% (2/13) normal squamous epithelium.CLU expression found 100% (31/31) normal endocervical glands.The Ki67 in SCC 13% (4/31) cases weak positive and 5% (1/19) adenocarcinoma. All cases small cell carcinoma revealed negative. No significant difference of the CLU expression rate between normal cervical epithelium, CIN II-III and SCC (p = 0.561). No significant difference of CLU expression rate between normal endocervical gland and adenocarcinoma (p = 0.119) as well. In Ki67, there was no significant difference of Ki67 rates between CIN 2–3 and normal squamous epithelium (p = 0.585). No significant difference of Ki67 expression rates between adenocarcinoma and normal squamous epithelium (p = 0.341). The expression of CLU and Ki67 had no correlation with FIGO stage, SCC antigen level, grade of differentiation, deep stromal invasion, and lymph node metastasis. Finally, the expression of CLU and Ki67 was not related to the 5-years DFS rates, and CLU expression was not correlated with Ki67 expression (rs = 0.500, p = 0.391). Conclusions: CLU and Ki67 was in lower rates in cervical cancer, and was not associated with any clinicopathological features. It is suggested that CLU and Ki67 have no distinct role in carcinogenesis. The further larger studies are needed to verify the results of this study. No significant financial relationships to disclose.
Treatment of advanced chemo-refractory epithelial ovarian cancer with aromatase inhibitor
Authors: Shaharyar A. , Shami N. , Zia N. , Hafeez M. , Rasheed H. , Saleem T. , Zulfiqar S. , Masood A. I. 
Published: August 2020

e16561 Background: In advanced epithelial ovarian cancer non-steroidal antiestrogens yields clinical responses in a significant number of patients. This raises the possibility of therapeutic effectiveness of aromatase inhibitors in epithelial ovarian cancer in post menopausal women. Therefore this study was carried out to document the effectiveness of an aromatase inhibitor, in advanced epithelial ovarian cancer patients with unknown hormone receptor status. Methods: From January 2006 to April 2007, a total of 38 patients were enrolled. Patients with histopathologically confirmed advanced epithelial ovarian cancer were included. Other eligibility requirements were: postmenopausal women, failure of third-line chemotherapy, age between 50–70 years, bidimensionally measurable disease, and CA-125 of more than 100 u/mL. An adequate hematologic, hepatic, and renal profile, and ECOG performance of 0–2 was required. Tablet letrozole 2.5 mg orally once daily was given for 03 months. CA-125 and Miller criteria were used for response evaluation. Results: No patient showed the evidence of complete or partial clinical response. Four patients had stable disease for 8 weeks. All patients showed progressive disease on week 12. Conclusions: In this small series no evidence of effectiveness of aromatase inhibitor letrozole in chemo refractory epithelial ovarian cancer is documented in patients with unknown hormone receptor status. It is, therefore, recommended that further study should only be carried out in the selected patient population with documented positive ER/PR hormone receptors. No significant financial relationships to disclose.
Capping the dose of paclitaxel in endometrial cancer patients: Does this affect clinical outcome?
Authors: Hanna R. K. , Shafer A. , Van Le L. 
Published: August 2020

e16563 Background: Various protocols recommend capping chemotherapy dosing of paclitaxel at 2m2 while other protocols dose paclitaxel according to actual body weight (ABW). In endometrial cancer where a significant portion of patients are obese this dosing difference may affect clinical outcome. We performed a retrospective review of patients with endometrial cancer who received paclitaxel and carboplatin after surgical staging. We compared patients who received paclitaxel dosed according to ABW with patients whose dose was capped at 2m2 to determine if differences in dosing affected progression free survival (PFS). Methods: Patients with endometrial cancer undergoing adjuvant treatment with paclitaxel and carboplatin from January 2000 to January 2008 were identified. Patient age, endometrial histology, stage, BSA, and paclitaxel treatment dose were collected and progression free survival was determined. Differences in outcome were compared and evaluated using student's t test. Results: 109 women were identified of whom 70 were treated according to their ABW (<2m2) and 39 obese patients received paclitaxel dose capped at 2m2. 95% of all the patients received the complete course of chemotherapy. PFS for both groups were 21.4±2.2 and 23.2±2.2 months with no significant difference in PFS (p = 0.62). When evaluating patients with endometrioid histology alone, no difference between patients receiving dosages according to ABW compared to those whose dosages were capped at 2m2 (25 patients vs. 19 patients, PFS 19.3±3.7 and 27.0±3.7 respectively, p = 0.16). However for patients with serous histology, PFS was significantly greater in those patients treated per their ABW when compared to patients capped at 2m2 (45 patients vs. 20 patients, PFS 30.2±3.2 and 19.6±3.5 months respectively, p = 0.05). Conclusions: There was no difference in PFS for patients with endometrioid cancer who were treated with ABW vs. capped doses of paclitaxel. However patients with serous histology experienced longer PFS when receiving paclitaxel dosed per ABW as compared to patients whose dose was capped at 2m2. This difference may reflect increased sensitivity of serous cancers to chemotherapy or other unknown biologic variables. Capping paclitaxel dosing in patients with serous endometrial cancers may affect their PFS. No significant financial relationships to disclose.
Gestational trophoblastic disease in Nepalese women managed in B. P. Koirala Memorial Cancer Hospital
Authors: Pariyar J. 
Published: August 2020

e16570 Background: Gestational trophoblastic disease (GTD) is potentially curable disease. Its incidence varies in different countries with high incidence reported in Japan (2/1000 pregnancies) and Mexico (2.5/1000 pregnancies). No studies have been reported regarding epidemiology, management and outcome of GTD in Nepal. Methods: The study was a descriptive case series. Case records of GTD patients attending B.P. Koirala Memorial Cancer Hospital, Nepal from 2001 to 2007 were analyzed. The main outcomes were measured in terms of duration, antecedent pregnancy, investigations, treatment and follow-up. Results: A total of 45 cases of gestational trophoblastic disease (GTD) were received from 26 districts of Nepal. The age of the patients ranged from 16 to 50 years with a mean age of 29.1 years (SD 9.4 years). Out of 45 cases 19 (43%) were of Tibeto-Burmese ethnic group and 15 (33%) belonged to Indo-Aryan ethnic group. There were 17 cases (37.8%) of hydatidiform mole, 6 were invasive mole (13.35%), 4 of persistent gestational trophoblastic tumour (8.8%) and 22 patients (48.8%) of choriocarcinoma. In 7 cases (15.5%) molar pregnancy had occurred in the first conception, another 7 cases (15.5%) had previous molar pregnancy and in 16 (35.5%) cases GTD had occurred following abortion. The most common presenting symptom was vaginal bleeding and 26 (57.8%) patients had anaemia. Theca Leuteal cyst was present in 11 (24.5%), 17 (37.8%) cases had lung metastasis, 4 (8.9%) had brain metastasis and another 4 (8.9%) had disseminated disease detecteted radiologically. Among the 45 cases 6 (13.3%) were treated with suction evacuation only; 9 (20%) underwent hysterectomy for uterine perforation, excessive hemorrhage and invasive mole. 28 (62.2%) cases underwent adjuvant chemotherapy among which 12 (26.6%) received single agent chemotherapy and 15 (33.3%) received EMA-CO regimen. Brain irradiation was required in a case with brain metastasis. Five (11.1%) cases with disseminated disease and high WHO risk score left the hospital against medical advice. There were 3 (6.7%) mortalities. 37 (82.1%) cases are in remission and follow-up. Conclusions: Early diagnosis of disease and proper management strongly influences the outcome of GTD. Even in disseminated state GTD can be cured. No significant financial relationships to disclose.
Surgical treatment for early cervical cancer: Experience at a cancer hospital in Nepal
Authors: Dangal G. 
Published: August 2020

e16575 Background: The purpose of this study was to find out the clinocopathologic characteristics, post-operative findings and complications of patients with early (up to stage IIA) cervical carcinoma who underwent radical hysterectomy. This study concentrates on the evaluation of our early experience in radical hysterectomy for cervical cancer in Nepal. Methods: This was a retrospective analysis of 48 patients who had radical hysterectomy with bilateral pelvic lymphadenectomy for early cervical cancer at the BP Koirala Memorial Cancer Hospital (BPKMCH) from September 2002 through September 2005. Characteristics such as chief complaint, disease staging and duration, intraoperative and postoperative complications, histopathological findings, need for blood transfusion, and duration of hospital stay were considered for analysis. Results: Patients’ age ranged from 28–67 years. Age group of 40–49 had highest number of patients (58.3%). Majority (62.5%) were premenopausal women who presented with abnormal vaginal bleeding (73%) as the chief complaint. More than half of them (56%) had FIGO stage IIA disease. Thirty-three percent had intraoperative and postoperative complications such as urinary problems, wound infection and vessel injury/ureteric injury. All needed blood transfusion, 42% needing four pints. The average duration of hospital stay was 11 days. Forty-four had squamous cell carcinoma and four had adenocarcinoma. Pelvic lymph node metastasis was found in 10 patients. Resected margins were adequate in 42 patients. Majority (62.5%) of the women were premenopausal and 56% of them had stage IIA disease. Conclusions: Although the primary treatment of early-stage cervical carcinoma involves either surgery or radiation therapy with or without chemotherapy, surgery (radical hysterectomy) was used for lower-stage disease and smaller lesions in fit and young patients in our resource-poor set-up. The complication rate seems to be higher in Nepal; however, it will decrease as more experience is gained. No significant financial relationships to disclose.
Acute toxicity to the skin and mucosa of radiotherapy alone versus radiotherapy in combination with cetuximab or chemotherapy in patients with head and neck cancer
Authors: Garcia-Huttenlocher H. I. , Timke C. , Jensen A. D. , Huber P. E. , Debus J. , Muenter M. W. 
Published: August 2020

e17007 Background: To evaluate acute toxicity of the skin and mucosa in patients with head and neck cancer who received Radiotherapy alone (RT) or in combination with cetuximab (IRT) or chemotherapy (CRT). Methods: We retrospectively analyzed 204 patients with head and neck cancer, treated between 2006 and 2008. RT was combined with cetuximab (n = 57), or with platinum-based chemotherapy (n = 99), 48 patients received RT alone. We included 149 male and 55 female patients with a median age of 62 years (range 22–92). Median radiation dose was 66 Gy (range 26.4–71.6Gy). 126 patients received intensity modulated radiotherapy (IMRT), 78 patients had conventional RT. Toxicity was assessed according to CTCAE Version 3.0. Results: Median follow-up was 9 months (range 1–34). Acute grade 3 toxicity of the skin was observed in 26% of IRT, 0% of RT, and 7% of CRT patients. Typical appearance of grade 3 skin toxicity in IRT was a massive confluent epitheliolysis of the RT field. Grade 3 mucositis appeared in 21% of IRT-, 12.5% of RT-, and 16% of CRT-patients. Rates of skin toxicity grade 3 were 8% in patients with IMRT and 15% in patients with conventional RT. Grade 3 mucositis was seen in 22% of the IMRT-patients and 8% of the patients with conventional RT. Cetuximab did not lead to a higher rate of RT interruptions as compared to RT and CRT. Early intervention and supportive care in case of high grade toxicity was performed for all patients. 8 weeks after RT all patients showed recovery from toxicity. Conclusions: Higher toxicity to the skin and to the mucosa occurred in the IRT group, and seems to be a specific side effect in the treatment of head and neck cancer patients with concomitant cetuximab and RT. But severity of toxicity may also be influenced by other factors such as RT technique. IRT patients need close observation and early intervention in case of therapy induced toxicity in order to prevent RT interruption, which might limit the advantage of cetuximab. Longer follow-up is needed to evaluate outcome and late toxicity of the different treatment groups. [Table: see text]