bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intraoperative intraperitoneal (IP) chemotherapy with cisplatin and escalated dose of epinephrine in patient with recurrent peritoneal carcinomatosis of ovarian cancer: A phase I study
Authors: Guardiola E. , Chauffert B. , Delroeux D. , Benoit L. , Causeret S. , Combe M. , Royer B. , Plaza J. , Heyd B. , Pivot X. 
Published: March 2020

16019 Background: IP epinephrine (E) has been shown to enhance the accumulation and antitumor activity of IP cisplatin in rats with peritoneal carcinomatosis (Duvillard et al. Int J Cancer, 1999). E induces a vasoconstriction of peritoneal vascular bed which limits platin peritoneal leakage and enhances drug penetration into tumor nodules. Results of a phase I study with the association of IP E and IP cisplatin in patient with refractory peritoneal carcinomatosis has been reported (Molucon-Chabrot et al, Anticancer Drugs, 2006). We conducted a phase I study to evaluate intraoperative IP chemotherapy with the association of cisplatin and escalated dose of E. Methods: 18 patients (pts) with recurrent ovarian cancer were enrolled. The median age was 56 years old (range 42–66). After an optimal cytoreductive surgery, IP chemotherapy was performed during surgery by filling twice the peritoneal cavity with 3 liters of an isotonic saline pre heated at 37°C and 90 mg of cisplatin associated with increasing concentrations of E during 1 hour. Results: E was escalated according to the following dosage: 0, 1, 2, 3 mg/L (3 pts by step). No toxicity was observed during and after intraoperative IP chemotherapy in the first 10 patients. The 2nd patient included in the 3 mg/L level of E experienced a tachycardia ≥ 120/min, ventricular extrasystoles (VES) ≥ 2/min, increase of troponine plasmatic concentration without significant electric sign of cardiac ischemia. The 3rd patient at this level experienced a tachycardia ≥ 120/min with ventricular VES ≥ 2/min and no increase of troponine concentration or electric sign of cardiac ischemia. According to the protocol design, 6 additional patients were included in the lower dose of 2 mg/L of E and no toxicity occurred. One can consider that the recommended dose of E was established. Conclusion: The combination of IP E with IP cisplatin in intraoperative chemotherapy after optimal cytoreductive surgery is feasible. The limiting toxicity was the cardiovascular effect which occurred with 3 mg/L dose of E. A phase II-III study is planned to investigate if IP chemotherapy adds to a second look surgery for the initial treatment of stage III ovarian carcinoma. No significant financial relationships to disclose.
Oxaliplatin and 5-fluorouracil in heavily pretreated patients with ovarian carcinoma: A well tolerated and efficient treatment
Authors: Rosa D. D. , Awada A. , Cardoso F. , Gil T. , Lebrun F. , Mano M. S. , Selleslags J. , Piccart M. J. , D'Hondt V. 
Published: March 2020

16028 Background: Recurrent ovarian cancer is an incurable disease. The prognosis of patients with platinum refractory disease is dismal. We present data from heavily pretreated patients with recurrent ovarian cancer to whom the Folfox regimen was administered. Methods: Patients with recurrent, resistant or refractory, pretreated ovarian carcinoma were eligible for this compassionate use program of oxaliplatin (85 mg/m2 in 2 hours) and leucovorin (200 mg/m2 in 1 hour) on day 1, followed by a continuous infusion of 5FU (2,600 mg/m2 in 48 hours), every 2 weeks. The objectives of the study were primarily to assess response rate and secondarily to evaluate the safety profile. Results: Fourteen patients were treated. Median age: 56 years (49–70). Performance status: 0 (n=4) and 1 (n=10). Median number of previous chemotherapy regimens: 5 (3–10) and previous platinum-based regimens: 2 (1–3). Median chemotherapy-free interval: 9.5 weeks (1–39). Median administered cycles of Folfox/patient: 8 (2–11 cycles). Responses according to RECIST criteria: 2 CR (14.5%), 2 PR (14.5%), 4 SD (29%) and 6 PD (43%). Responses according to CA125 Rustin's criteria: 4 CR (29%), 2 PR (14.5%), 5 SD (35.5%) and 3 PD (21%). Grade 1/2 and 3 peripheral neuropathy: 10 (71%) and 2 (14.5%), respectively. There were no grade 4 adverse events or deaths due to the treatment. Conclusions: Folfox is a valuable option for heavily pre-treated patients with ovarian cancer, with an overall response rate of 29% (95% CI 15.2% to 41.8%), disease stabilization in an additional 29%, and a manageable toxicity profile. These results support the use of Folfox as salvage treatment for patients with ovarian carcinoma. No significant financial relationships to disclose.
Prognostic impact of histological response after neoadjuvant chemotherapy in patients with stage IIIC/IV ovarian cancer undergoing complete cytoreductive surgery at the time of interval debulking surgery
Authors: Morice P. , Ferron J. , Rey A. , Zafrani Y. , Uzan C. , Gouy S. , Castaigne D. , Duvillard P. , L'Homme C. , Pautier P. 
Published: March 2020

16032 Background: The aim of this study was to evaluate the prognostic impact of histological response at the time of interval debulking surgery (IDS) in patients treated with neoadjuvant chemotherapy (NACT) for unresectable advanced-stage ovarian cancer (ASOC). Methods: A retrospective study was conducted in our institution to select cases fulfilling 3 following inclusion criteria: 1. Patients with unresectable (evaluated in most of them with initial surgery + biopsies) ASOC. All patients had residual disease > 2 cm after such initial surgery; 2. At least 3 courses of platinum + paclitaxel NACT; 3. Patients undergoing after NACT an IDS with absence of macroscopic residual disease at the end of the debulking surgery. IDS was followed by post-operative chemotherapy. Patients were classified into 3 groups according to the histological response (in the peritoneum & nodes) after NACT: group 1: no residual disease in peritoneum; group 2: persistent residual disease but with histological signs of chemoactivity (marked histological changes) and group 3: persistence of at least 1 site with no changes in the tumor (persistence of very active cells). Survival was compared between these 3 groups. Results: Fifty-eight patients treated between 1997 and 2004 fulfilled inclusion criteria (49 had stage IIIC and 9 stage IV disease). Respectively 47 & 11 patients received 3–4 or 5–6 courses of chemotherapy before IDS. Respectively 11, 11 and 36 patients were in groups 1, 2 & 3. The median time of follow-up was 41 months. Three-year overall survival in groups 1, 2 & 3 was respectively: 81%, 39% and 62% (no statistical difference). Three- year event-free survival in groups 1, 2 & 3 was respectively: 46%, 18% and 19% (p=.04 between group 1 versus 2+3). Conclusions: These results suggest that the degree of histological response have a limited impact on the survival of patients when complete debulking surgery is achieved at IDS. The degree of tumor cell viability after initial chemotherapy is not a reliable marker for modifying chemotherapy after debulking surgery in such patients. No significant financial relationships to disclose.
Role of multivisceral cytoreductive surgery in patients (pts) with recurrent ovarian cancer (ROC): Who will not benefit from radical tumor debulking?
Authors: Koensgen D. , Mustea A. , Weidemann H. , Neumann U. , Neuhaus P. , Pirvulescu C. , Kozo D. , Oskay-Oezcelik G. , Lichtenegger W. , Sehouli J. 
Published: March 2020

16036 Background: Despite improvement in surgery and adjuvant chemotherapy most pts with ovarian cancer (OC) experience a relapse within 2 years after first diagnosis. For primary OC a standard concensus on optimal staging and surgical guidelines is established. The role of radical tumor debulking surgery in ROC is not clearly defined. Aim of this study was to analyze clinical parameters for prediction of operability and impact on overall survival in ROC. Methods: Within the framework of the international project “Tumor bank Ovarian Cancer“ (TOC) a systematic prospective surgical and histomorphological tumor documentation for ROC was performed. Results: Between september 2000 and december 2006, 307 multivisceral operations on 254 pts with ROC were performed consecutively in our department. Median age was 55 years (19–83), median follow-up 15 months (1–75). 34.8% of pts experienced first relapse of OC. Overall, 96.3% of pts received a platinum-based first-line chemotherapy, whereas 73.4% were platinum sensitive. In 55% of pts first relapse surgery was performed. In 41.4% of pts complete macroscopic tumor resection was achieved, associated with a significantly better recurrence-free (median 20.6 vs 13.2, p=0.001) and overall survival (median 42 vs 12 months, p<0.001) compared to pts with any postoperative residual tumor. In multivariate analysis, complete tumor resection was associated with the absence of tumor burden in the upper abdomen (p=0.001) and absence of ascites (p=0.05). Prognostic factors for postoperative survival were: tumor resection (0 cm vs > 0 cm, p<0.001), intraoperative volume of ascites (0 ml vs > 0 ml, p=0.006) and response to platinum-based first-line therapy (platinum sensitive vs platinum-resistant, p=0.006). Conclusions: Radical tumor debulking in patients with ROC is associated with a low postoperative morbidity and mortality. Complete mascroscopic tumor resection is correlated with a significant better long-term prognosis and influenced by tumor spread and presence of ascites. Pts with ROC will not benefit from multivisceral cytoreductive surgery in case of platinum resistance to first-line chemotherapy, presence of intraoperative ascites and postoperative residual tumor. No significant financial relationships to disclose.
Weekly combination chemotherapy of docetaxel and carboplatin and 5-FU in recurrent cervix cancer
Authors: Elkerm Y. M. , Elsaid A. , Elnemr M. 
Published: March 2020

16038 Background: The current phase II study assessed docetaxel/carboplatin/5FU given weekly for 24 weeks, for recurrent uterine cervix cancer. Methods: Fourty patients with histologically confirmed, recurrent uterine cervix cancer were enrolled. The patients eligible for this study had histologically confirmed, recurrent uterine cervix cancer. . Patients received weekly docetaxel 20 mg/m2 and carboplatin area under the curve (AUC) 2 weekly with bolus 5FU 500 mg/m2. The response status of the patients was assessed using the common ECOG response criteria. Results: 40 patients were entered in this study. The distribution of intial stage at first presentation was IB, 6 ; IIB, 16; IIIB, 10; IVB, 8. There were 30 squamous cell carcinomas, 6 adenocarcinomas, 4 adenosquamous cell carcinoma. : All patients were evaluable, and completed all planned therapy. The most frequent maximum toxicities during chemotherapy were Grade 2 mucositis with neutopenia. Nonhematological toxicity was generally mild, except for ubiquitous complete alopecia. Responses after 6 months included 6 patients with complete responses, 22 patients with PR and 12 patients with SD. No progression of disease was observed. Conclusions: This regimen was feasible, safe, and particularly well tolerated. Early Phase II outcomes revealed promising activity in patients completing all treatment. No significant financial relationships to disclose.
Gestational trophoblastic disease: Experience at a tertiary care center from a developing country
Authors: Hariprasad R. , Ganessan K. , Gupta A. , Kumar L. , Kumar S. , Bhatla N. , Kriplani A. , Kochupillai V. 
Published: March 2020

16041 Background: We retrospectively analyzed case records of patients diagnosed to have Gestational Trophoblastic Disease (GTD) to determine clinical characteristics, risk groups, treatment outcome, and reproductive function post treatment. Methods: Between Jan 1991 to Dec 2005, 102 patients (mean age: 28.2 years, range 19–50) were diagnosed to have GTD. 35 patients were nulliparous and 8 had prior molar pregnancy. Vaginal bleeding was the most common presenting symptom (77.5%). The antecedent pregnancy was vesicular mole in 50%, abortion - 34.3%, ectopic pregnancy - 4% and term pregnancy in 11.8% patients. The mean value of B hCG was 1225386 mIU/ml. The histopathology (n=85) was complete mole in 30, partial mole - 28, invasive mole- 9, PSTT -1 and choriocarcinoma in 17 patients. 68(66.7%) patients had non-metastatic disease. Sites of metastasis were - lung (38.2%), vagina (11%), brain (8.8%), liver (6.9%) and kidney, Urinary bladder and peritoneum in one patient each. According to modified WHO risk scoring - 78(76.5% had low risk and 24 (23.5%) were high risk. Results: Eighty-seven (85.3%) patients received chemotherapy using methotrexate with leucovorin (n=63), EMA/CO (n=19) and BEP (n=5). 77/87 (89.5%) achieved complete remission (CR) ; the response rate was higher in non-metastatic GTD (p<0.05). Two of 7(28.6%) patients with liver and 5/9 (55,6%) of brain metastasis achieved CR. Two patients had grade III oral mucositis and diarrhoea with methotrexate. One patient died of Methotrexate hypersensitivity. 19 patients received second line chemotherapy using EMA/CO (n=11), EMA/EP (n=2), BEP (n=1), actinomycin-D (n=1) and MAC (methotrexate, actinomycin D and Cyclophosphamide) n=1; 14 patients achieved CR. At a mean follow up of 180 months, 5-year survival for patients with low risk is 100% and that of high risk is 95%. Eight patients had recurrent disease including recurrent molar pregnancy in four. 16 patients had 24 successful deliveries after completion of treatment and 10 of them were primiparae. No fetal abnormalities were found. We did not observe second malignancy or other therapy related sequele. Conclusions: Present study confirms excellent outcome for patients with gestational trophoblastic disease. The potential for childbearing is well maintained. No significant financial relationships to disclose.
Effect of simultaneous inhibition of MEK and PI3K/Akt pathways on paclitaxel sensitivity in ovarian cancer
Authors: Kigawa J. , Kawaguchi W. , Itamochi H. , Kanamori Y. , Oishi T. , Shimada M. , Sato S. , Sato S. , Terakawa N. 
Published: March 2020

16046 Background: Paclitaxel (PTX) is one of the key drugs for ovarian cancer treatment. PTX activates the Raf-mitogen-activated protein kinase kinase (MEK) and phosphatidylinositol 3’-kinase (PI3K) pathways that lead to cell survival pathways. The purpose of this study was to clarify whether and how the inhibitors of MEK and/or PI3K affect the sensitivity to PTX in ovarian cancer cells. Methods: We treated five ovarian cancer cell lines in combination with PTX and MEK- [PD98059 (PD)] and/or PI3K-inhibitor [LY294002 (LY)] and assessed cell viability, apoptosis, and the expression of phosphorylated (p) MEK and pAkt. The sensitivity of the cell lines to PTX was determined by 3-(4,5- dimethylthiazol-2-yl) -2,5-dyphenyltetrazolium bromide (MTT) assay. The level of protein expression was analyzed by western blot analysis. The drug-induced apoptosis was assessed by Annexin V-FITC staining. Additionally, KOC-2S was injected to intraperitoneal cavity of nude mouse. The effect of combined treatment on the survival in xenograft model was investigated. Results: The levels of pMEK and pAkt protein expression were higher in PTX resistant cell lines (KOC-2S and KFTx) than that in sensitive cell lines (KF, SHIN-3, SK-OV-3). Treatment of PTX induced MEK activation in all five ovarian cancer cell lines. The combination of PTX with either PD or LY led to additive effect on cell growth inhibition. In contrast, synergistic effect was observed in the combination of PTX with PD and LY. Furthermore, apoptotic cells were significantly increased after exposure to PTX and both inhibitors in comparison with other treatment conditions, such as PTX alone, PTX with either PD or LY. The level of pMEK induced by PTX was down-regulated by PD. Interestingly, the level of pAkt was up-regulated by the combination of PTX with PD, which was reduced by LY. Treatment with PTX, PD, and LY prolonged survival in an ovarian cancer xenograft model (p < 0.01). Conclusions: The present study suggests that simultaneous inhibition of MEK and PI3K/Akt pathways enhances the sensitivity to PTX in ovarian cancer. The combination of PTX with MEK- and PI3K-inhibitor may be a new treatment strategy for ovarian cancer. No significant financial relationships to disclose.
Phase I trial of pegylated liposomal doxorubicin (PLD) and cyclophosphamide (CPM) in patients with relapsed platinum- resistant epithelial ovarian carcinoma (EOC)
Authors: Floquet A. , Cany L. , Dutin J. P. , Jaubert D. , Dupouy C. , Brouste V. , Mathoulin-Pélissier S. 
Published: March 2020

16057 Background: Most patients (pts) with EOC recur despite platinum-taxane based first line chemotherapy. Response to second line chemotherapy is limited, and usually related to time between the end of first line treatment and relapse. For early relapses, treatment with non cross resistant drugs or treatment with a different toxicity profile is necessary. Thus, following results of the Gordon study (JCO 2001 Jul 15;19(14):3312–22), a phase I trial of PLD and CPM was planned in patients with EOC who relapsed within 12 months of first line therapy. Methods: This multicenter phase I included 21 pts, PS < 2, age = 18 and = 70, no previous anthracycline, with recurrent EOC (one measurable lesion and/or CA125 elevation RECIST criteria) within 12 months after platinum-taxane first line chemotherapy. Six dose levels were planned : Twenty-one patients were included (3 each at L1, 2, 3 and 4 at L4, 5 and 4 more at L3 ; 18 evaluable patients, 3 excluded due to early PD). No intra patient dose escalation was allowed. Cycles are repeated every 28 days. Toxicity observed on the first 2 cycles. Results: Median age of pts: 59 yrs (22–70). Median platinum-free interval: 6.4 months (0.9–11.7); 71 cycles were administered; 2 DLT NCI G3 were observed at level 4: 1 oesophagitis and 1 stomatitis. No limiting haematological nor skin toxicity was observed. Median follow-up was 25.7 months, 4 surviving pts, 1 with a CR and 3 pts with disease. Conclusions: The combination of CPM and PLD is feasible. The recommended dose for further phase II trial is PLD 40 mg/m2 and CPM 600 mg/m2 every 28 days. [Table: see text] No significant financial relationships to disclose.
Ovarian adenocarcinoma in teenagers and young adults: A clinical challenge
Authors: Gercovich N. , Carnaval S. , Negro F. , Santillán D. , Abal M. , Morgenfeld E. , Rivarola E. , Deza E. Gil , Gercovich F. G. 
Published: March 2020

16070 Background: Ovarian cancer (OC) appears at an average age of 63, and is uncommon in younger patients (pt), with only about 5% being diagnosed below 30 years of age. The aim of this study is to analyze the onset and prognosis of ovarian adenocarcinoma (OA) in teenagers and young adults treated at the IOHM. Methods: From Oct 87 through Nov 06, 467 pt were diagnosed with OC. Twenty six pt (5,35%) were young adults or teenagers. Ten out of the 26 pt had OA, while the other histological types were as follows: 7 pt Germ cell tumors- 5 pt Borderline - 2 pt stromal tumors - 1 pt neuroendocrine - 1 pt undifferentiated. Characteristics of the Population: Median age: 22 years (range 15–29). Symptomatology: 6 pt presented pain and pelvic tumor, two pt malignant ascites, and one skin nodules. Stages: I (4 pt), III (3 pt), IV (2pt), Not registered: 1 pt. Histological Subtype: Serous: 2pt, Endometroid: 1pt, Mucinous: 4 pt. Non-specified adenocarcinoma: 3 pt; Histological Grade: 1: 4pt; 2: 2pt, 3: 3pt. Not registered: 1 pt. Results: All pt were surgically treated (optimal surgical cytoreduction: 5/ 9). All pt received first line chemotherapy based on a Platinum combination. The average follow up time was 58 months (range: 4–162). Five pt are still alive (Median Duration of Survival 78 months (range 12–162) and four of them are free of the disease (Stage I: 3pt and Stage III: 1pt). Conclusions: 1- The OA in teenagers and young adults is uncommon and only stands for 2% of the total ovarian tumors (10/467). 2- In contrast with its adult counterpart, the ascites as an initial symptom was only present in two of our cases. 3-Three out of four stage I pt and one stage III pt are still alive and disease free after 60 months. No significant financial relationships to disclose.
Prognostic factors in uterine sarcoma: A clinicopathologic and immunohistochemical (IHC) study of 30 cases
Authors: Al-Safi F. , Al Kushi A. , Ameeri S. , Al Merri N. 
Published: March 2020

16071 Background: The objective of this study is to examine the prognostic relevance of traditional clinical, pathological and IHC features of uterine sarcoma (US). Methods: The study population consisted of thirty cases of US treated at our institute. Twenty- two cases are HGS (11 leiomyosarcoma, and 11 carcinosarcoma) and eight cases are LGS (5 mullerian adenosarcoma and 3 low grade endometrial stromal sarcoma). Clinical and pathological data including patient's age, parity, menopausal status, tumor cell type, lymphovascular invasion, nuclear grade, stage and mitotic index. Serial sections were immunostained with antibodies for p53, bcl-2, estrogen receptor (ER), Her2 and c-kit. The clinicopathological and IHC features were analysed by using Kaplan-Meier method for constructing survival curves, and log-rank statistic for survival curves comparison. Multivariate analysis was performed using Cox regression modeling. Results: The mean follow-up period of patients is 32 months (range 1- 120). Twelve (55%) patients with HGS died of the disease and none of the LGS group. In the HGS group, stage (p=0.01), myometrial invasion in early stage tumor (p=0.04), and lymphovascular invasion (p=0.043) were significant predicators of patient outcome in univariate analysis. Similarly, tumor cell type, ER, p53 and bcl-2 expression showed statistical significant correlation with tumor-specific survival (p=0.0039, p=0.001, p=0.03, and p=0.04, respectively). ER and bcl-2 expression were associated with better outcome and the opposite for p53 expression. In a multivariate analysis, only the tumor stage and cell type had independent statistical significance (p=0.04, and p=0.035, respectively). Overexpression of p53 and Her2 were observed in 40% and 60% of carcinosracomas respectively and not seen in any of the other tumors. The c-kit immunostain showed focal and weak staining in 40% of carcinosarcoma and only in 33% of leiomyosarcoma. None of LGS had this marker. The ER was expressed only in the LGS group. Conclusions: This study demonstrates that stage and tumor cell type are the most important prognostic indicators of patient outcome in US. IHC markers such as ER, p53, c-kit, and Her2 can be useful ancillary tools to discriminate between HGS and LGS in difficult cases. No significant financial relationships to disclose.