bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II trial of temozolomide as first-line treatment for patients with advanced gynecological sarcoma: A Spanish Group for Research on Sarcomas (GEIS) and Spanish Ovarian Cancer Research Group (GEICO) study
Authors: Garcia Del Muro X. , Poveda A. , Buesa J. M. , Martinez Trufero J. , De Sande L. M. , Calvo E. , Escudero P. , Lopez Pousa A. , Fabregat X. , Casado A. 
Published: March 2020

9570 Background: Temozolomide (TMZ) as an extended schedule showed activity in the subgroup of patients (pts) with pretreated gynecological sarcoma (GS) in a prior phase II study (Cancer 2005;104:1706) as well as in a series of GS pts treated in a compassionate use program (Proc ASCO 2005;9030). The purpose of the present study was to assess the activity of TMZ as first-line chemotherapy in pts with GS. Methods: Pts with non-previously treated advanced GS and non-irradiated measurable lesions were eligible for this phase II study. TMZ was administered orally at a dose of 75 mg/m2/day continuously for 6 weeks, every 9 weeks. The study was conducted using a Simon’s two-stage design. The initial planned sample size was 25, but after an amendment, this was increased to include 25 pts with leiomyosarcoma (LMS) histology. Primary endpoint was response rate (RECIST). Results: From October 02 to September 05, 33 pts were included at 16 centers. At present, 32 pts are evaluable (1 too early). Median age was 59 (39–75). Primary tumor sites were uterus (31) and ovary (2). Histologic types were: LMS (28), mixed mullerian tumor (3), endometrial stromal sarcoma (ESS) (2). Histologic grade: III:16, II:6, I:2, unknown:9 pts. PS: 0:12, 1:15, 2:6 pts. A total of 57 cycles were administered (median 2, range 1–3). Toxicity (pts): thrombocytopenia G-IV:2, GIII:1; neutropenia G-IV:1; nausea G-III:2, G-II:5; vomiting G-III:2, G-II:6; stomatitis G-III:1, G-II:2; asthenia G-III:1, G II:5. There were 3 CR, 3 PR and 6 SD, giving an overall response rate of 19% (95% CI, 5–32%). Responses were seen in LMS (5) and ESS (1) and lasted 4+, 6, 7+, 7+, 9+ and 17+ months. Median time to progression was 3.3 months (95% CI, 1.7–4.9). Conclusions: TMZ at this extended schedule was active against GS, producing in some pts long-lasting responses, and might be a well-tolerated alternative in selected pts, warranting further investigation. No significant financial relationships to disclose.
Gene expression identifies heterogeneity of soft tissue sarcomas
Authors: Skubitz K. M. , Pambuccian S. , Skubitz A. P. 
Published: March 2020

9574 Background: Soft tissue sarcomas (STS) exhibit heterogeneity in their clinical behavior, even within histological subtypes. Histological appearance is determined by gene expression. However, metastatic propensity, tumor growth, and response to chemotherapy may be determined by gene expression patterns that do not correlate well with morphology. One approach to identify heterogeneity is to search for markers that correlate with differences in tumor behavior. Alternatively, subsets may be identified based on gene expression patterns independent of knowledge of clinical outcome. We have reported gene expression patterns that distinguish two broad classes of clear cell renal carcinoma (ccRCC) independent of histological appearance, and other patterns that can distinguish heterogeneity of serous ovarian carcinoma (OVCA). Methods: In this study, gene expression in 41 samples of STS (including malignant fibrous histiocytoma (MFH), leiomyosarcoma, liposarcoma, and synovial sarcoma), 12 samples of fibromatosis, and 17 normal tissues was determined at Gene Logic Inc. (Gaithersburg, MD) using Affymetrix GeneChip U_133 arrays containing approximately 40,000 genes/ESTs. Gene expression analysis was performed with the Gene Logic Genesis Enterprise System Software. Results: Hierarchical clustering using two gene sets, one that distinguished two subsets of ccRCC, and a second set that distinguished two subsets of OVCA, both generated subgroups within the STS that for some, but not all, subtypes correlated with histology, and also suggested the existence of subsets of MFH. Both gene sets also identified the same two subsets of the fibromatosis samples. In addition, genes expressed uniquely in MFH, leiomyosarcomas, and liposarcomas among these and 512 samples from 17 other normal tissue types were identified. Conclusions: The ability to sub-classify histological subtypes of STS, including identifying possible subsets of MFH, using gene sets derived from studies of two different carcinomas suggests that these subgroups may have biological significance. Some of the genes identified as over-expressed in particular subsets of STS compared with a variety of normal tissues may reflect possible targets to which anti-tumor therapy could be directed, and may also be useful for sub-classification of STS. No significant financial relationships to disclose.
Phase 3 study of atamestane + toremifene vs. letrozole in advanced breast cancer
Authors: Goss P. E. , Bondarenko I. N. , Manikhas G. N. , Pendergrass K. B. , Miller W. H. , Blanchett D. , Lang W. , Langecker P. 
Published: March 2020

LBA525 Background: This study addresses the principle of “complete estrogen blockade” by combining atamestane, an investigational steroidal aromatase inhibitor (AI) with toremifene, an approved first line therapy. The primary objective was to assess whether atamestane + toremifene could improve on the time to disease progression achieved with letrozole alone. Methods: This was a multinational randomized, double blind, double dummy phase 3 clinical trial. Eligible women were postmenopausal with advanced breast cancer (ABC), estrogen and/or progesterone receptor positive. Prior adjuvant hormonal therapy was permitted only if completed >12 months prior to enrollment. Subjects received either atamestane 500 mg per day with toremifene 60 mg per day (A+T), or letrozole 2.5 mg per day (L). The primary endpoint was time to progression (TTP), log-rank test comparison on all randomized patients. Secondary objectives included objective response (OR), overall survival, and time to treatment failure (TTF). The study had 80% power to detect a 25% increase in TTP assuming a TTP of 9.4 months in the L population. Results: 865 patients with locally advanced (9%) or metastatic disease (91%) were randomized: 434 to A+T and 431 to L. Baseline characteristics were: mean age 64 years (S.D. = 9); ECOG Status 0 = 30%, 1 = 60%, 2 = 10%; prior adjuvant hormonal therapy 13%; prior adjuvant chemotherapy 20%. Sites of metastases and number of sites were well balanced between arms. The median TTP was identical in the two arms: 11.2 months (p < .92, log-rank chi square). The hazard ratio (L/A+T) for TTP was 1.00 (0.92–1.08, Cox proportional hazards 95% CI); for TTF was 0.99 (0.92–1.06) and for overall survival was 0.98 (0.87–1.11). OR occurred in 30% of patients on A+T and 36% of patients on L (p < 0.1, likelihood ratio chi square). Most frequent AEs (A+T vs L) were asthenia (11% vs 12%), increased weight (12% vs 10%), and hot flushes (10% vs 11%). Serious AEs were 10% vs 11%. Conclusions: While our study did not demonstrate increased TTP for A+T compared with L, this is the first endocrine therapy to be equally effective as letrozole as first line therapy in ABC. Both treatments were equally well tolerated. Unlike the ATAC trial, addition of an anti-estrogen did not decrease the efficacy of the AI. Further study of combination AI + SERM is warranted. [Table: see text]
SWOG 0012, a randomized phase III comparison of standard doxorubicin (A) and cyclophosphamide (C) followed by weekly paclitaxel (T) versus weekly doxorubicin and daily oral cyclophosphamide plus G-CSF (G) followed by weekly paclitaxel as neoadjuvant therapy for inflammatory and locally advanced breast cancer
Authors: Ellis G. K. , Barlow W. E. , Russell C. A. , Royce M. E. , Perez E. A. , Livingston R. B. 
Published: March 2020

LBA537 Background: Between 10-1-02 and 12-01-05, SWOG 0012 accrued patients to a two-arm randomized trial, with formal participation from NCCTG and CTSU participation by other cooperative groups. Arm 1 gave A at 60 mg/m2 and C at 600 mg/m2 q 3 wk IV for 5 cycles, arm 2 A at 24 mg/m2/wk × 15 IV and C at 60 mg/m2/day PO for 15 wk with G at 5 mcg/kg/day × 6/7 weekly. Both groups then received T at 80 mg/m2/wk × 12, and proceeded to surgery with pCR by NSABP criteria at the primary site as the endpoint. A total of 372 were randomized, and we report here on 265 patients (pts) evaluable for outcome, including those who did not proceed to surgery. In arm 1, pCR was seen in 17% vs 27% in arm 2 (p = .06); when adjusted for hormone receptor status (ER-PR- in 49% on arm 1, 41% on arm 2) and disease type (locally advanced vs inflammatory), the odds ratio in favor of arm 2 is 1.98 (95% CI 1.05–3.74, p = .034). For ER- PR- pts, pCR rates for Arm 1 vs 2 were 26 vs 43%, while for those with ER or PR+, pCR rates were 9 vs 14%. Inflammatory pts showed a striking difference in pCR rates for arm 1 vs arm 2 (12 vs 33%, p = .033). HER 2 status (+ in 29%) did not predict response or interact with treatment. Grade 3/4 toxicities (arm 1 vs 2, %) were as follows: hand-foot syndrome (0 vs 13), neutropenia (47 vs 16), neutropenic infection (1.8 vs 0.6), stomatitis (2 vs 11), and nausea/vomiting (11 vs 5). Toxicity from T was grade 3 neuropathy in 10%, with grade 3 or 4 neutropenia in 12%. There were no treatment-related deaths. Continuous or “metronomic” chemotherapy with AC is superior to standard intermittent AC, and the pCR rate reported for the continuous arm is the highest reported in a cooperative group experience for this patient population. [Table: see text]
In vivo proton magnetic resonance spectroscopic (PMRS) evaluation: Emerging tool to solve the diagnostic dilemma in soft tissue sarcoma management
Authors: Kar M. , Deo S. S. , Kumar V. , Sharma U. , Jagannathan N. R. , Dannishad K. A. , Deo V. , Shukla N. K. , Datta Gupta S. , Thulkar S. 
Published: March 2020

10020 Objective: Presently grade is the most important factor used to decide the soft tissue sarcoma management. But it is always very difficult to assign a pathologic grade because of discordance rate is 30–40%, even among experienced sarcoma oncopathologists. Again histopathology has the disadvantages of being invasive, subjective and insensitive to tumour heterogeneity. This emphasizes the need for an objective and accurate assessment of histologic type and grade of sarcoma. The aim of this study is to evaluate the correlation of in vivo proton magnetic resonance spectroscopic findings with histopathological features and validate its diagnostic efficacy in management of different types of soft tissue sarcomas. Methods: PMRS Study was performed at 1.5Tesla MRI machine with a surface coil appropriate for the location of the lesions in 25 patients. Single-voxel (SVS) study has been done in 10 cases and chemical shift imaging (CSI) study characterised the heterogeneity of the tumor in 15 cases by using point - resolved spectroscopic sequence (PRESS) with echo time TR=2,000 / TE = 30, 135 & 270 msec. The choline peak, identified at 3.2 ppm in spectra was considered as significant which shows the activity of the tumour. MRS results and histopathologic findings were correlated and P < 0.001, considered being significant. Results: Choline peak was found in 17 out of 17 patients with malignant soft tissue tumours where as three patient with benign and five treated malignant soft tissue tumour patients with no residual disease did not show any choline. In vivo spectroscopy here shows sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 100% each. Conclusion: Choline peak in MRS study can predict the grade, margin status (especially CSI) and tumour activity in recurrent and / or residual soft tissue sarcoma. Most important findings here was that without using any contrast medium in study the choline peak in CSI spectroscopic evaluation could show the tumor activity at the margin of the tumor which is very important point for evaluation of residual or recurrent or completion of the surgical excision of the tumor A major study should be done to validate its efficacy for routine use in oncology. [Table: see text]
Female patients with soft tissue sarcoma are at a higher risk for developing breast cancer
Authors: Jiveliouk I. , Geva R. , Inbar M. , Merimsky O. 
Published: March 2020

10071 Background: An increased incidence of MPM has been reported in association with STS. In a series of 1350 adults with STS almost 10% were diagnosed with additional primaries. The incidence of breast cancer (BC) in the general population is 97/105,(Israel-Cancer-Registry) and the incidence of STS is 1.5/105 (Enzinger&Weiss). It is expected that approx. 1.5/105 × 97/105 of the general population will have both BC and STS. Methods: A retrospective search of the database of approx. 1,350 adult STS patients, who were referred, diagnosed, or treated at our center between 1995- 2005. Results: A group of 132 patients (F=62) with STS had at least one additional malignancy. Twenty-five (25/62=40%) had BC, before or after STS. A family history of malignancy was reported by 8/25 patients (32%), 3 with a specific breast cancer family history. STS types varied. Sixteen (16/25) patients had breast cancer as their first primary, 9 as their second or third. Of 17 patients with first primary BC, the sarcoma appeared in the RT field in 2, and in 1 it appeared in a lymphedematous ipsilateral arm. Of eight patients with first primary sarcoma, only one got chemotherapy prior to the diagnosis of BC. Median interval between 1st to 2nd malignancy was 6.9 years (0.7–31y) when the BC was diagnosed first, and 3.8y (0–47y) when the BC was the second. Exposure to carcinogens, or therapeutic radiation and cytotoxics, given for the 1st tumor prior to the 2nd tumor, was recorded in 58%. The incidence of BC among all patients (females + males) with STS-first (in our database) followed by a second malignancy is 8/58 (14%), or 7/23 (30%) female patients with STS-first, or 25/890 (3%) of all female patients with STS in the registry of STS. The incidence of STS among the BC patients is rather low, and most of the cases in this series are not therapy related (14/17). The median survival of patients with BC-first was 312 months, versus 383 months for STS-first (p=NS). Among patients with BC-first, the median survival of patients with RT related sarcoma was 265 months, versus 312 months for RT unrelated STS (p= 0.6). Conclusions: Second primary BC in patients with STS-first is higher than the expected incidence of BC for this population. Screening for BC should be incorporated into the regular follow-up of patients with STS. No significant financial relationships to disclose.
Hypoxia-inducible-factor 2 alpha mediates cisplatin resistance in the lung adenocarcinoma cell line A549
Authors: Rose F. , Eul B. , Kwapiszewska G. , Marsh L. , Kamlah F. , Seeger W. , Grimminger F. , Lohmeyer J. , Haenze J. 
Published: March 2020

10573 Background: Hypoxia in solid tumors is associated with cancer progression, metastasis and resistance to chemotherapy. The hypoxia inducible factors (HIF-1a and HIF-2a) are key players in the response to hypoxia affecting angiogenesis, proliferation and apoptosis. Here we investigated the role of HIF-1a and HIF-2a in cellular resistance to cisplatin in non small lung cancer cells (A549). Results: Hypoxia reduced the efficiency of cisplatin treatment on A549 cells via enhancement of drug efflux activity. In addition, hypoxia induced the hypoxia-responsive-element (HRE) reporter gene assay, demonstrating the transcriptional activity of HIF-1a and HIF-2a. Administration of cisplatin further increased the reporter activity under both normoxic and hypoxic conditions. This correlated with the induction of HIF-2a protein expression upon cisplatin treatment in normoxia and hypoxia, whereas HIF-1a was suppressed. Additionally, cisplatin induced nuclear accumulation of HIF-2a. Suppression of HIF-2a by RNA interference potentiated the sensitivity to cisplatin treatment in hypoxic A549 cells. In vivo growth delay assay gave analogues results for subcutaneous A549 tumors treated with cisplatin and suppression of HIF-2a. In comparison, other cytostatic drugs such as doxorubicin and gemcitabine differed with respect to HIF signalling. Doxorubicin induced both HIF-1a and HIF- 2a. Cellular sensitivity to doxorubicin was increased via suppression of HIF-1a and HIF-2a. Gemcitabine appeared to act independent of HIF. The underlying mechanism of hypoxia-induced resistance was due to increased mRNA expression of drug resistance proteins such as MDR1, MRP1 and LRP. These were found to be HIF-2a but not HIF-1a dependent. Conclusion: This data identified HIF-2a as a key player in the hypoxia induced cisplatin resistance and show on the molecular level that HIF-2a is a credible target for therapeutic strategies. No significant financial relationships to disclose.
The impact of waist-to-hip ratio (WHR) on survival in metastatic breast cancer patients treated with aromatase inhibitors (AIs)
Authors: Artac M. , Samur M. , Bozcuk H. , Afacan B. , Ozdogan M. 
Published: March 2020

1070 Background: Aromatase inhibitors represent a novel hormonal therapy for breast cancer. Aromatase is expressed in the ovaries, brain, bone and, adipose and breast tissue. Elevated WHR, representing a higher abdominal fat distribution, has been associated with both the development of and mortality from breast cancer. Therefore, we aimed to identify whether abdominal fat distribution could affect the outcome in metastatic breast cancer patients treated with AIs. Methods: A total of 46 metastatic breast cancer patients treated with first line hormonal therapy were enrolled in this study. Pretreatment body weight, height, BMI and WHR were measured. Estrogen, progesteron and c- erb-B2 receptor status were also evaluated in analyses. Univariate and multivariate Cox regression analyses, and Kaplan Meier survival curves subjected to log rank testing were utilized for the survival analyses. Forward likelihood ratio was used for the multivariate selection process. A P value < 0.05 was considered to be significant. Results: Median age was 51 years (range 28 - 75). 36 patients were treated with letrozole and 10 patients with anastrozole. Median body weight, height, WHR and BMI were found to be 68.5 kg (range 46 - 115), 156 cm (range 137 - 167), 0.91 (range 0.7 - 1.2), and 28.7 (range 18 - 45), respectively. Factors associated with overall survival in the univariate analysis were age, c-erb-B2 expression intensity (+++ versus others by immunohistochemistry), and WHR, whereas only WHR retained significance in the multivariate analysis. Likewise, predictors of progression free survival were c-erb-B2 expression intensity and WHR. However, none of these factors was significant in the multivariate analysis. Median overall survival figures were 472 days versus unreached for patients with a WHR of <0.92 and =0.92 (Log rank statistic = 9.76, P = 0.002). Similarly, the corresponding progression free survival figures for patients with a WHR of <0.92 and =0.92 were 423 versus 1,004 days (Log rank statistic = 6.37, P = 0.012). Conclusions: This is the first report examining and suggesting the value of abdominal fat distribution in relation with benefit from AIs in metastatic breast cancer. Our results should be validated in larger series. No significant financial relationships to disclose.
Paradoxical effects of medical reassurance in patients with breast cancer
Authors: Shields C. G. , Corbin K. , Weiss M. , Lambert D. M. , Griggs J. J. 
Published: March 2020

11018 Objective: The purpose of this study was to investigate the impact of medical reassurance on distress and fear of recurrence in women with ductal carcinoma in situ (DCIS) and early stage invasive breast cancer. Methods: We conducted an anonymous survey on the website of breastcancer.org, a non-profit organization. Recruitment to the survey was through a general invitation to “Tell us about your breast cancer experience.” The survey inquired about disease and treatment characteristics and contained the Positive and Negative Affect Scale (PANAS) and the Concerns about Recurrence Scale. Participants were also asked if they had been told by any of their medical providers that they had a “good cancer,” “favorable cancer,” or “better kind of cancer.” Analyses were performed to investigate the impact that being told one has or had a “good cancer” and feelings of reassurance, isolation, distress, and guilt. Results: A total of 362 participants with breast cancer completed the survey, 143 of whom had DCIS. Of these, 147 (41%) reported having been told that they had a “good cancer” by one or more of their medical providers, most often by their surgeon (83%) and/or their medical oncologist (61%). Among those told they had a good cancer, 67% reported that being told this led to their feeling moderately-to-extremely “reassured.” Many respondents, however, also reported moderate-to-severe negative responses to being told that they had a good or favorable cancer_feeling “isolated” (38%), “distressed” (43%), “scared” (61%), and “guilty” (30%). Conclusions: Although telling patients they have a “good” or “favorable” cancer leads to feelings of being reassured in the majority of women, such terms may also contribute to distress, feelings of isolation, and guilt among many patients who otherwise might enjoy a good prognosis quality of life. Providing reassurance is a complex process. Further research into effective ways of communicating reassurance is warranted in order to minimize distress and enhance quality of life. No significant financial relationships to disclose.
Results of trastuzumab targeted therapy in metastatic breast cancer (MBC): The Sultanate of Oman experience 2002–2006
Authors: Khalifa A. , Faris M. , Al-Bahrani B. 
Published: March 2020

11518 Background: The first random study of incidence of Her-2 over expression among Omani breast cancer patients was carried out by the Medical Oncology Department, the Royal Hospital in 2001. The incidence was reported as 40% (higher than international published figures). The Herceptest was routinely performed on all new patients for a whole year (2004) and the incidence was found to be 36%. Trastuzumab was approved for use in the Sultanate of Oman in 2002, since then a total of 26 patients with metastatic breast cancer received Trastuzumab, the results are presented. Methods: Prospective, single arm, single centre experience. Patients with confirmed metastatic breast cancer (at presentation or after adjuvant treatment), HER-2 positive (+++ by Herceptest, or FISH positive), age > 18, ECOG PS ≤ 2, LVEF = 50% and adequate renal & liver function, were included. Treatment consisted of trastuzumab as single agent or in combination with chemotherapy as indicated. A loading dose of 8mg/kg was followed by 6mg/kg q3 weeks. The endpoints were response rate (RR) progression free survival (PFS) and survival (OS). Results: a total of 26 patients were included between October 2002-October 2006, median age was 45.5years (27–60), 12 patients presented with metastasis at first presentation and 14 had metastatic disease 6 months or more after finishing adjuvant chemotherapy. The median number of received cycles was 10 (range 4–30), the overall response rate was 77% (54% CR and 23% PR), the median survival 15 months (range 4–36m), median Time to Progression 9m (range 4–33m). Six patients (23%) developed brain metastasis while on herceptin. There were 8 events (disease related deaths) during the study period. Conclusions: The incidence of Her-2 +ve breast cancer in Omani patients is slightly higher than the reported figures in international studies. The response to trastuzumab in metastatic disease is comparable to other similar studies. No significant financial relationships to disclose.