bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variance in physician attitudes toward androgen deprivation therapy initiation for biochemical cancer recurrence
Authors: Hemmerich J. A. , Ahmed F. , Bylow K. , Stadler W. , Dale W. 
Published: March 2020

15626 Background: The optimal timing for starting Androgen Deprivation Therapy (ADT) for patients with recurrent prostate cancer (PCa) remains uncertain. In 2004, the American Society of Clinical Oncology deemed the evidence insufficient to recommend early ADT initiation. Recent evidence shows a slight survival benefit to recurrent PCa patients with high risk features; however, early initiation can prematurely reduce patients’ quality of life without providing benefit. This pilot study surveys physician attitudes and practices regarding ADT initiation at a single institution. Methods: Physicians (n=20), including 7 attendings and 13 fellows, who treated biochemically- recurrent PCa patients enrolled in a companion study completed a survey about clinical experience, knowledge of recommendations, and attitudes regarding decisions to start ADT. They also rated the importance of sixteen factors potentially contributing to the decision. Results: Consistent with the ASTRO definition, forty-five percent answered, that three consecutive PSA-rising tests constitute recurrence. For patients with high risk features (Gleason > 7, doubling time < 10 months), 55% said ADT should be started immediately, while only 15% noted that the literature remains unresolved on this issue. For patients without high risk features, 100% would defer ADT. The two factors rated most important in determining ADT initiation timing were PSA doubling time (100%) and patient preferences (95%). Conclusions: Our preliminary data suggest that even within one institution, there is variance in physicians’ definitions of PCa recurrence and the correct treatment strategy. Despite the lack of definitive data on the benefit of early ADT initiation even for high risk patients, over 50% said such patients should start immediately. No significant financial relationships to disclose.
Expression of EGFR, HER-2 and p53 predictive of prognosis in muscle-invasive bladder cancer
Authors: Sakr W. , Marur S. , Che M. , Heilbrun L. , Smith D. , Powell I. , Pontes E. , Cher M. , Vaishampayan U. 
Published: March 2020

15637 Background: The significance of over expression of Erb-1 (epidermal growth factor receptor/ EGFR) and Erb-2 (Her-2) has been reported in various tumors. The aim of this study was to investigate the correlation of the expression of EGFR, Her-2 and p53 with relapse free survival (RFS) and over all survival (OS) in patients with muscle invasive bladder cancer Methods: All patients with muscle invasive bladder cancer diagnosed at our institution between1993and 2004 were considered for the study. Immunohistochemical staining for EGFR, Her2 and p53 performed on formalin-fixed paraffin-embedded archival tissue was evaluated as positive or negative without knowledge of clinical outcome. Survival data determined by reviewing patients medical records were correlated with the staining results. Results: Of the 46 patients who qualified for the study, 40 had slides interpretable for Her 2 and p 53 staining and 38 had slides interpretable for EGFR staining. 35 of 38 were EGFR +ve, 22/40 were Her-2 +ve and 12/40 were p53+ve. The median age of the 46 patients was 67.5 years with a male/female ratio of 60% and 40%. 83% had clinical Stage 2; of those 42%, 23%, and 35% had pathological stages T2, T3 and T4 respectively. Six of 46 (13%), received adjuvant therapy. Tumor histology was pure transitional carcinoma in 56%, or with other components (squamous or adenocarcinoma) in 44%. Median follow-up was 48.8 months for RFS and 44.9 months for OS. Patients with positive EGFR had a median RFS of 34.8 months and median OS of 59.8 months. In patients with negative EGFR, median RFS and OS were not yet reached. Her 2 positive patients had median RFS of 19.2 months compared to 63.8 months in Her-2 negative patients. Her-2 negative patients had median OS of 59.7 months while median was not reached in Her 2 positive patients. Conclusions: While the differences are not statistically significant, the trends observed warrant prospective investigation of the prognostic significance of these markers in a larger population of muscle invasive bladder cancer patients. No significant financial relationships to disclose.
Monotherapy with a tumor-targeting mutant of S. typhimurium cures orthotopic metastatic mouse models of human prostate cancer
Authors: Hoffman R. M. , Zhao M. , Geller J. , Ma H. , Yang M. 
Published: March 2020

15641 Background: The evidence that bacteria have a therapeutic effect on tumors has been accumulating since the 19th century. In recent years, there has been renewed interest to develop bacteria that target necrotic tumor areas. However, this approach requires combination with cytotoxic chemotherapy for efficacy. Toward the goal of effective tumor-targeting bacteria as monotherapy, we have developed Salmonella typhimurium leu-arg auxotrophs (A1-R), which enable the bacteria to grow in viable as well as necrotic areas of tumors but not in normal tissue. Methods: In the current study, we determined the efficacy of A1-R on metastatic PC-3 human prostate tumors orthotopically implanted in nude mice. Ten of 20 orthotopically-implanted nude mice served as untreated controls and were followed until death. Ten mice were given the S. typhimurium A1-R weekly intravenously, beginning at 2 weeks when the tumor was first externally visible due to expression of green fluorescent protein. Survival time was compared to the untreated mice. Results: Of the 10 mice with the PC-3 tumors injected weekly with S. typhimurium A1, 7 were alive and well at the time the last untreated mouse died. Four A1-R-treated mice remain alive and well 6 months following implantation. Ten additional non-tumor-bearing mice were used to determine toxicity of S. typhimurium A1-R which were injected weekly. No toxic effects were observed. Conclusions: The approach described here, where bacterial monotherapy could cure metastatic prostate tumors, is a significant improvement over other bacterial tumor-therapy strategies that require combination with toxic chemotherapy. The results also suggest the clinical potential of tumor-targeting bacteria that can grow in the viable as well as necrotic areas of the tumor. Since human prostate cancer eventually becomes non-androgen- dependent similar to PC-3 tumors, genetically-altered bacteria represent a novel potential treatment for this disease. No significant financial relationships to disclose.
Treatment of metastatic papillary renal cell carcinoma with immunochemotherapy with interleukin-2, interferon-alpha and 5- fluorouracil
Authors: Herrmann E. , Brinkmann O. A. , Bode M. E. , Bierer S. , Köpke T. , Hertle L. , Wülfing C. 
Published: March 2020

15644 Background: Combined immunochemotherapy with interleukin-2 (IL-2), interferon-alpha (IFN-a) and 5-fluorouracil (5-FU) is an established first-line therapy for metastatic renal cell carcinoma (RCC). However, data on histologic parameters predictive of clinical benefit are rare. Methods: Treatment courses of 164 patients consisted of IFN-a at 9 x 106 IU on day 1 of weeks 1 and 4 and days 1, 3, 5 of weeks 2 and 3; and at 18 x 106 IU on days 1, 3, 5 of weeks 5–8. Interleukin-2 was administrated at 18 x 106 IU twice daily on days 3–5 of weeks 1 and 4; and at 9 x 106 IU on days 1, 3, 5 of weeks 2 and 3. Additionally, patients received 5-FU at 750 mg m-2 on day 1 of weeks 5–8. In 153 patients, radical nephrectomy had revealed 22 cases of papillary RCC (pRCC, 13.4%) and 131 cases of clear cell RCC (ccRCC, 79.9%). In the remaining 11 (6.7%) their disease was inoperable. The overall response rates were evaluated according to WHO criteria. Results: For ccRCC and inoperable disease, responses of 34.4% and 27.3% after one cycle and 28.8% and 16.7% after two cycles, respectively, were noted. In contrast, no patient with pRCC showed any response after two cycles of combined immunochemotherapy. Conclusions: No objective response was seen in patients with pRCC. Hence, immunotherapeutic agents must be questioned in this histologic subtype. No significant financial relationships to disclose.
Clinical outcome of patients (pts) with taxane-resistant (TR) hormone-refractory prostate cancer (HRPC) treated with second-line cyclophosphamide (CP) -based metronomic chemotherapy
Authors: Nelius T. , Klatte T. , de Riese W. , Filleur S. 
Published: March 2020

15647 Background: For pts with TR HRPC no standard chemotherapeutic treatment exist. In this study we evaluate the efficacy of CP-based metronomic chemotherapy in this pt population. Methods: Pts with metastatic HRPC with disease progression under docetaxel-based chemotherapy were eligible. The primary endpoint was PSA response. Secondary endpoints were time to progression (TTP), survival and toxicity. Low dose CP (50 mg/d) and dexamethasone (1 mg/d) were administered orally in a metronomic manner. Treatment was continued until disease progression. Results: Between February 2005 and May 2006 17 pts were enrolled in this study. The median follow-up was 12 weeks (range: 4–60). Median Age was 68 years (range: 42–85). Median PSA at study entry was 134 ng/ml (range: 46.0–6554). 9 pts had a PSA response (medium 44.4%), 4 pts = 50% and 5 pts < 50%. 8 pts had a PSA progression. The medium time to maximal response was 12 weeks (range: 4–36). TTP/survival for pts with PSA response and PSA progression was 24/60 weeks and 4/4 weeks, respectively. 3 pts of the progression group showed a decrease in PSA doubling time. 5 pts reported a decrease in bone pain after 4 weeks treatment. No grade 3 and 4 toxicities were noted. Conclusions: In this study, low-dose metronomic administered CP demonstrated efficacy as second line treatment in pts with TR HRPC. The treatment was well tolerated and almost without toxicity. The mechanism of action of low dose CP involves inhibition of tumor angiogenesis secondary to inhibition of dividing endothelial cells in tumor associated blood vessels. Dexamethasone may also have antiangiogenic properties by inhibiting the production of vascular endothelial growth factor. Further investigation regarding an antiangiogenic treatment strategy for HRPC are therefore of great interest. No significant financial relationships to disclose.
Long-term survival in patients with para-aortic lymph node metastasis with systematic retroperitoneal lymphadenectomy followed by adjuvant chemotherapy in endometrial carcinoma
Authors: Hiura M. , Nogawa T. , Matsumoto T. , Yokoyama T. , Shiroyama Y. , Wroblewski J. , Hirata E. 
Published: March 2020

16011 Background: The purpose of this study was to assess modified radical hysterectomy including systematic pelvic and para- aortic lymphadenectomy followed by adjuvant chemotherapy in patients with para-aortic lymph node metastasis in endometrial carcinoma and to identify the multivariate independent prognostic factors for a long-term survival over the past 10 years. Methods: Between December 1987 and December 2002, we performed modified radical hysterectomy with bilateral salpingo-oophorectomy including systematic pelvic and para-aortic lymphadenectomy, and peritoneal cytology in 284 endometrial carcinoma patients who gave an informed consent at the Department of Gynecologic Oncology of Shikoku Cancer Center. The patients with a tumor confined to the uterus (stage Ic and II) were treated by 3 courses of CEP (cyclophosphamide 750 mg/m2, epirubicin 50 mg/m2, cisplatin 75 mg/m2) regimen 3–4weeks apart, extrauterine lesions involving adnexa and/or pelvic lymph node (PLN), and para-aortic lymph node (PAN) metastasis were treated by 5 and 10 courses, respectively. Multivariate analysis was performed for the prognostic factors and actuarial technique for the survival rate. Results: PLN and PAN metastasis were 9.2% (26/284) and 7.4% (21/284), respectively. The univariate analysis of prognostic factors revealed that FIGO clinical stage, histology, myometrial invasion, adnexal metastasis, lymphvascular space invasion, tumor diameter, peritoneal cytology and retroperitoneal lymph node (RLN) metastasis were significantly associated with 10-year overall survival. A multivariate analysis showed that adnexal metastasis (p=0.0418) and lymphvascular space invasion (p=0.0214) were significantly associated with 10-year overall survival. The 5- and 10-year survival in patients with negative and positive para-aortic lymph node were 96%, 72% and 93%, 62%, respectively (p=0.006). Conclusions: We conclude that surgery with systematic pelvic and para-aortic lymphadenectomy followed by adjuvant chemotherapy might improve a long-term survival in patients with PAN metastasis in endometrial carcinoma. No significant financial relationships to disclose.
Evaluation of gemcitabine versus cisplatinum as an adjunct to radiotherapy in locally advanced carcinoma uterine cervix
Authors: Bhatt M. L. , Matin A. , Srivastava M. , Pant M. C. , Srivastava K. , Gupta S. , Rastogi M. , Singh U. , Chhavi D. 
Published: March 2020

16012 Background: Locally advanced carcinoma cervix patients are treated by a combination of external beam radiation and brachytherapy. Concurrent chemo-radiotherapy has been an active area of investigation in such patients. In this present study, we have compared two chemotherapy drugs- cisplatinum vs gemcitabine along with radiotherapy in loco-regionally advanced carcinoma cervix with the purpose of evaluating loco-regional disease control and tolerability of these combinations. Methods: This study was undertaken on 65 biopsy-proven patients with stage IIb- IIIb carcinoma cervix. All patients were treated with 50 Gy of external beam radiation with 2 Gy per fraction, 5 days a week followed by intra-cavitary radiotherapy (ICRT). Dose of ICRT delivered by high dose rate brachytherapy was 18 Gy by either of the two schedules, viz. 3 fractions of 6 Gy at weekly interval or 2 fractions of 9 Gy each at one week apart. The concurrent chemotherapy was either inj. Cisplatinum 35 mg/m2 IVI weekly (control group), or inj. gemcitabine 150 mg/m2 IVI weekly (Study group). Results: A total of 65 age and stage matched patients were recruited in the two arms of the study. We analyzed sixty patients who completed the above treatment protocol with 32 patients in control group and 28 in study group. Eighty-nine percent patients in study group had complete response (CR) to the above combination treatment vs. 72% CR in control arm (p< 0.05). However, overall response rate (CR+ PR) was similar in both the groups (96% in study group vs. 100% in control group). No patient in both the groups had grade IV skin reaction with only one patient in study group developing grade III skin toxicity. Grade III gastrointestinal (GI) toxicity was higher in study group as compared to controls (14% vs. 3%) with none of the patients experiencing grade IV GI toxicity. No other significant toxicity was encountered in this study. Conclusions: We can conclude that synchronous chemo-radiotherapy using either gemcitabine or cisplatinum as radiation sensitizer is feasible in locally advanced carcinoma cervix with similar overall response rate and acute toxicity profile with a significantly higher complete response rate when gemcitabine is used as a chemotherapeutic drug. No significant financial relationships to disclose.
Persistence of EpCAM-positive disseminated tumor cells after platinum-based chemotherapy in the bone marrow of patients with primary ovarian cancer
Authors: Wimberger P. , Heubner M. , Kimmig R. , Scheulen M. E. , Kasimir-Bauer S. 
Published: March 2020

16023 Background: The impact of chemotherapy on disseminated tumor cells (DTC) in ovarian cancer is still unknown. Therefore we evaluated in 30 patients with primary ovarian cancer, undergoing radical tumor debulking surgery, (1) the influence of first-line chemotherapy with carboplatinum and paclitaxel on DTC elimination in bone marrow (BM) and peripheral blood (PB), (2) the coexpression of the epitelial antigen EpCAM on DTC and (3) the impact on progression free survival (PFS). Methods: DTC were detected in PB (20ml) and bilateral BM aspirates (10ml) using density gradient centrifugation and immunocytochemistry, applying the anti-cytokeratin antibody A45-B/B3. EpCAM-positive DTC were analyzed by using the antibodies HEA-125-FITC and Ber-EP4-FITC. PFS was estimated using the Kaplan-Meier method and statistically evaluated using a two-sided log-rank test. A significant increase or decrease of DTC was assessed if the difference was = 2 DTC. Results: Before chemotherapy, we identified DTC in 16% of PB samples with a mean number of 2 cells (range 1–3) and in 50% of BM samples with a mean number of 3 cells/9x10E6 BM cells (range 1–8). After chemotherapy, DTC were detected in PB in only one patient but still in 50% of BM samples with a with a mean number of 17 cells/9x10E6 BM cells (range 1–100). In BM, chemotherapy completely eliminated DTC in 30% of the patients, no significant change was documented in 47% and a significant enhancement of DTC was shown in 33%, including 8 patients (27%) who had no DTC before chemotherapy. In case of significant increase of DTC, patients showed a trend for reduced PFS (12.8 months ± 0.7; mean PFS ± SEM) in comparison to patients with no increase (19.3 months ± 1.4) or decrease of DTC (p=0.07). DTC, persisting after chemotherapy, co-expressed EpCAM. Conclusions: It has to be considered, whether these patients with persisting EpCAM-positive DTC in BM might profit from an additive immunotherapy e.g. by the intraperitoneal application of a trifunctional antibody targeting EpCAM, CD3 and accessory cells. No significant financial relationships to disclose.
A phase I study of imatinib mesylate and paclitaxel in patients with advanced (stage IIIC/IV) or recurrent uterine papillary serous carcinoma (UPSC)
Authors: Slomovitz B. M. , Ramondetta L. M. , Johnston T. , Lu K. H. , Broaddus R. R. , Muller P. , Iyer R. B. , Burke T. W. , Gershenson D. M. , Wolf J. 
Published: March 2020

16025 Background: Uterine serous carcinoma (USC) is a rare, aggressive uterine tumor biologically distinct from typical endometrial cancers. Imatinib mesylate (IM)-associated kinases (kit, abl, PDGFR-B) are overexpressed and activated in most tumors from patients (pts) with USC. Single agent paclitaxel (TAX) has a good response rate but short duration of response in pts with USC. The purpose of this study was to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of escalated doses of IM with a fixed dose of TAX. Methods: Pts with newly diagnosed (stage IIIC/IV) or recurrent USC were eligible (pts were required to have tumors that expressed at least one of the IM-targeted kinases by immunohistochemistry). Measurable disease was not required. TAX was administered at 175 mg/m2 every three weeks. One dose reduction to 135 mg/m2 was allowed. IM was given daily (400 mg, 500 mg or 600 mg). A 3+3 design was implemented. Pts with measurable disease were treated until progression or treatment associated toxicity. Pts with no measurable disease were treated for six cycles. Results: 11 pts were enrolled. The median age was 62 years (47–79). A total of 50 cycles were administered. Three pts were treated at the first dose level (400 mg), 6 pts treated at the second dose level (500 mg), and 2 pts were treated at the highest dose level (600 mg). Three DLTs were observed (1 at 500 mg level and 2 at 600 mg level) including: rash, neutropenia, and fatigue. IM 500 mg daily and TAX 175 mg/m2 every three weeks was the MTD. There were 3 serious adverse events not related to treatment (infection, dyspnea, pain). Neutropenia was the most common grade 3 or 4 toxicity but only one patient required TAX dose reduction. 8 pts were evaluated for efficacy (2 with measurable disease, 6 with no measurable disease). 1 (of 2) pts with measurable disease had a partial response and was treated for 13 cycles. Of the 6 pts with no measurable disease, 2 recurred (5 and 10 months). The median disease free interval for the pts without recurrent disease was 22 months (6–30). Conclusion: Combination therapy of IM and TAX is well tolerated with minimal side effects in pts with advanced or recurrent USC. Initiation of the phase II component of this study is warranted to better evaluate efficacy. No significant financial relationships to disclose.
ErbB3 protein expression in serous ovarian carcinomas of elderly women
Authors: Hirsch M. S. , Liu J. , Drapkin R. , Lee H. , Matulonis U. A. 
Published: March 2020

16026 Background: Ovarian carcinoma is the leading cause of death due to gynecologic malignancies, and older age at the time of diagnosis has been suggested to correlate with poorer outcome. Recent studies suggest that expression of ErbB3, a member of the epidermal growth factor receptor family, is associated with decreased survival. The goal of this study was to examine ErbB3 protein expression with a tissue microarray (TMA) comprised of advanced papillary serous (PS) ovarian carcinomas, and to correlate results with clinical information to evaluate for expression differences in younger and older women. Methods: A high density TMA (with 4 cores per primary tumor) was constructed by retrospective review of PS ovarian carcinoma cases seen between 1999 and 2005. Patients were divided into 2 cohorts based on age (=65 and =55 at diagnosis). Only cases of stage III or IV disease were included, and patients with BRCA mutations were excluded. Clinical data were obtained by chart and database review. TMA sections were immunostained for ErbB3, and expression was correlated with age, stage, and overall survival. Results: 136 primary tumors were available: 72 in the =65 group, 64 in the =55 group. Tumors from the =65 cohort were significantly less likely to express ErbB3 (16.7%) when compared to the ≤55 cohort (51.6%) (p<0.0001). Patients whose tumors expressed ErbB3 had decreased median survival (33.6 months) compared to ErbB3 negative cases (47.3 months), but these results were not statistically significant (p=0.10). ErbB3 expression correlated in a borderline significant manner with stage (dichotomized as IIIa/IIIb vs. IIIc/IV) at the time of diagnosis (stage IIIa/b 11.8%+ vs. stage IIIc/IV 36.1%+; p=0.055). Multivariate analysis with respect to age, stage, and ErbB3 status did not reveal ErbB3 to be a statistically significant predictor of poor outcome in this data set. Conclusions: These results demonstrate that PS ovarian carcinomas in patients aged =65 at the time of diagnosis are significantly less likely to express ErbB3 than those ≤55. Correlation between ErbB3 expression and more advanced stage at the time of diagnosis bordered on significance. There was a non-significant trend towards decreased overall survival in both univariate and multivariate analyses in patients whose tumors exhibited ErbB3 expression. No significant financial relationships to disclose.