bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utility of total body FDG PET/CT imaging in the initial staging of soft-tissue sarcoma
Authors: Roberge D. , Hickeson M. , Charest M. , Turcotte R. E. 
Published: August 2020

10531 Background: Soft-tissue sarcoma spreads predominantly to the lung. It is currently unclear how often PET scan will detect metastases not already obvious by chest imaging or clinical examination. Methods: Soft-tissue sarcoma cases were identified retrospectively. Ewing's sarcoma, rhabdomyosarcoma and GIST tumors were excluded as were patients imaged for follow-up, response assessment or recurrence. Patients all had had a diagnostic chest CT scan as part of their staging. Directed studies were requested to follow-up on abnormal findings in the clinical history or physical examination. All charts and pre-treatment imaging were reviewed retrospectively. Results: From 2004 to 2008, 75 patients met the criteria for this review. These 75 patients had total body FDG-PET/CT imaging on routine initial staging of their sarcoma. The median age was 51. In 21% of cases, the primary tumor had been removed by excisional biopsy or unplanned excision prior to staging. 97% of the previously unresected primary tumors were FDG avid (SUV ≥ 2). 81% of tumors were high-grade (FNCLCC Grade 2–3). The primary tumor was stage T2b in 68% of cases. The most common primary site was the lower extremity (55%). The most common pathological diagnoses were: leiomyosarcoma (21%), liposarcoma (19%) and synovial sarcoma (17%). At the end of staging, 17% of patients were considered to have metastatic disease. PET scans were negative for distant disease in 64/75 cases. Seven of these 64 cases had metastatic disease on chest CT (negative predictive value 89%). 8 PET scans were positive - of these, 4 patients were already known to have metastases, 2 were pathologically proven false positives and 1 was a new finding of a pulmonary metastasis (sensitivity 46%). Three patients had indeterminate PET scans (subsequently none developed metastatic disease). Two incidental benign parotid tumors were found. In total, only 1 patient was upstaged by the PET imaging (1.3%). In addition, PET did not alter management of patients already know to have M1 disease (no new organ sites identified). Conclusions: Although PET scans may be of use in specific circumstances, routine use of FDG PET imaging for detection of metastatic disease as part of the initial staging of soft-tissue sarcoma adds little to chest CT scanning and is unlikely to alter management. No significant financial relationships to disclose.
Adjuvant therapy with imatinib in gastrointestinal stromal tumor (GIST) patients with intermediate or high risk: Analysis from a single-center contrast study
Authors: Li J. , Gong F. J. , Li J. , Wu W. A. , Shen L. 
Published: August 2020

10556 Background: Imatinib benefits the patients with metastatic GIST but whether it is effective in the adjuvant setting after complete tumor resection of primary GIST is questionable. Methods: Patients who had undergone complete tumor resection with intermediate or high risk of recurrence (define) were enrolled in a single-center non-randomized open contrast study. Patients had adjuvant therapy with imatinib (400mg once a day) for 3 years commencing within 12 weeks of tumor resection, or had follow-up alone. We performed c-kit and PDGFRA mutation analysis for patients with archival tumor samples. The primary objective was recurrence-free survival (RFS) and the second objective was correlation of gene mutation profile with efficacy of adjuvant therapy. Results: One hundred and five patients were enrolled: 56 patients in adjuvant therapy group and 49 patients in control group. Median follow-up was 30 months (range 12–62); Median treatment duration in adjuvant therapy group were 20 months (range 12–36); There was relatively higher 1-year and 2-year RFS in the adjuvant therapy group compared with the control group (100% vs 89.8%,94.4% vs 60.0%) (Log-RankP< 0.001). Hazard risk was 0.13 (95% CI 0.039–0.438, P= 0.001) in Cox proportional hazard regression model. For further sub-group analysis, Log-rank and Cox regression analysis showed that adjuvant therapy could significantly decrease recurrence risk in patients with high risk disease (define)(2-year RFS: 91.5% vs 46,2%, Log-Rank: P<0.001, HR:0.107 (95%CI 0.031–0.370), P<0.001). c-kit and PDGFRA mutation were analyzed in forty-nine patients. There was a better survival benefit from adjuvant therapy for patients with c-kit exon 11 mutation. Conclusions: Adjuvant therapy with imatinib can improve 1-year and 2-year recurrence-free survival for patients with an intermediate or high risk of recurrence after complete tumor resection. No significant financial relationships to disclose.
KIT and PDGFRAmutation status and their immunohistochemical (IHC) expression profile of gastrointestinal stromal tumor (GIST) patients treated with imatinib (IMT): Seven-year single-center experience
Authors: Koh Y. , Kim H. , Lee H. , Lee K. , Oh D. , Kim J. , Im S. , Kim T. , Kim W. , Bang Y. 
Published: August 2020

10558 Background: Previous studies suggested the role of KIT and PDGFRAmutations on treatment outcome of GIST with IMT, but results are heterogeneous. IHC value of PDGFRA and PDGFRB is not established. Methods: We included patients (pts) treated with IMT as a first line therapy for metastastic or relapsed GIST between 2001 and 2008. Tumor DNA was extracted to investigate the mutation status of KITexon 9, exon 11, PDGFRA exon 12 and 18. IHC stain of c-KIT and PDGFRA/B was performed. We assessed the correlation between the treatment outcome, genetic status and IHC results. Results: A total of 85 pts (M:F=49:36, median age 58.4 years) received IMT 400 mg daily. Location of primary disease included stomach (33), small bowel (34), rectum (10), esophagus (1), and omentum/mesentery (7). Complete and partial responses were achieved in 6% and 62% of pts respectively, while 5% of pts had progressive disease. During median follow up of 28.1 months, estimated median PFS was 39.8 months. KIT exon 11 and 9 mutations were detected in 64% and 5% respectively. Exon 11 mutations included 44 deletions, 2 insertions, 5 substitutions and 3 deletion/insertions. PDGFRA exon 12 and 18 mutations were detected in 2% respectively. Positive rate of c-KIT, PDGFRA and PDGFRB using IHC was 96%, 21%, and 26% respectively. PDGFRA and PDGFRB were co-expressed (p=0.001). PDGFRA mutation did not correlate with PDGFRA/B expression. Clinical response was not different according to the mutation status or IHC expression. PFS of KIT exon 11, KITexon 9, PDGFRA mutants and pts without detectable mutations were not different (p=0.397). Pts with KIT exon 11 balanced mutations (substitution or deletion/insertion) showed longer PFS compared with pts with unbalanced mutations (deletion or insertion) (p=0.014) or pts without exon 11 mutations (p=0.033). Median PFS was shorter in pts lacking c-KIT (p=0.001) expression. PDGFRA/B expression did not influence PFS. Conclusions: Balanced mutation of KIT exon 11 predicted longer PFS, while lack of c-KIT protein expression predicted shorter PFS for GIST pts treated with first line IMT. PDGFRA and B were co-expressed without predictive value. No significant financial relationships to disclose.
Regulational effects of breast cancer stromal cells and normal breast stromal cells on MCF-7 mammosphere formation
Authors: Zhang F. , Xu Y. , Song C. , Ma Y. , Nan F. , Wang H. , Lin S. , Huang M. , Zhang Y. 
Published: August 2020

1056 Background: It is well known that microenvironment plays an important role in tumor progression so we investigated the regulatory effects of breast cancer stromal cells (BCSCs) and normal breast stromal cells (NBSCs) as microenvironment on MCF-7 mammosphere formation. Methods: MCF-7 cells were cultured in suspension to generate mammospheres. The proportion of CD44+CD24- cells was assessed by flow cytometry and the expression of Wint1, notch1, β-catenin, CXCR4, SOX2, and ALDH3A1 was detected by real-time PCR. The stromal cells were purified and identified by immumohistochemistry. BCSCs or NBSCs and MCF-7 cells were co-cultured via Transwell system, the volumes and numbers of mammospheres and the mammosphere-forming efficiency (MFE) were calculated and the expression of Wnt1, β-catenin, Notch1 were detected. Results: The proportion of CD44+CD24- cells in mammospheres and MCF-7 cells was 10.4% and 2.1% (p < 0.05), respectively. Real-time PCR analysis suggested that Wint1, notch1, β-catenin, CXCR4, SOX2, and ALDH3A1 genes in the mammosphere cells were with higher levels than MCF-7 cells by about 2.25, 2.45, 1.72, 4.68, 4.25, 5.38 fold, respectively (p < 0.01). The stromal cells purified were identified as fibroblasts by α-SMA,Vimentin and fibroblast special protein antibody via immumohistochemistry. The time of mammosphere's formation was earlier, the volumes of mammospheres were bigger, and the MFE was higher than control group. The expressions of Wnt1 in co-culture group were significantly upregulated 1.27, 3.18 folds than control group, respectively, while the β-catenin was 1.22, 1.75 folds; Notch1 was 1.31, 2.09 folds; and CXCR4 was 1.73, 2.77 folds, respectively. Conclusions: Mammosphere cells contained higher propotion of breast cancer stem cells and expressed higher levels of cancer stem cell related genes. BCSCs can promote the mammosphere-forming efficiency and upregulate the expression of cancer stem cell related genes. No significant financial relationships to disclose.
Response to sirolimus in combination to tirosine kinase inhibitors (TKI) in three cases of PDGFRA-D842V metastatic gastrointestinal stromal tumor (GIST)
Authors: Piovesan C. , Fumagalli E. , Coco P. , Palassini E. , Dileo P. , Morosi C. , Gronchi A. , Casali P. 
Published: August 2020

10565 Background: In GISTs, specific KIT/PDGFRA mutations lead to differential drug sensitivity. The exon 18 PDGFRA-D842V mutation is known to be resistant to imatinib and sunitinib. Activation of tyrosine kinase receptor involves a signal transduction pathway involving AKT/mTOR, RAS, phosphoinositide 3-kinase and BRAF. We therefore used the mTOR inhibitor sirolimus in three pts with a PDGFRA-D842V metastatic GIST. Methods: Since August 2007, 3 PDGFRA-D842V GIST pts (age: 54–56–63 yrs) have been treated with sirolimus (2–3 mg/day) in combination to TKI (PKC412 in one pt, and imatinib in 2 pts), on an individual use basis. Two pts were progressing on imatinib, while the third pt was treated with imatinib + sirolimus upfront. Sirolimus blood levels were assessed. Results: Two pts had a Choi's response 6 and 3 mos, respectively, after starting the combination. In the first pt, responding to sirolimus + PKC412, the latter drug had been started alone, with no response. The last pt, undergoing imatinib + sirolimus, has a short follow-up. Disease was stable at 2 mos, although clinical improvement was noticed, and therapy is ongoing. The first pt underwent surgery of residual peritoneal disease after 13 mos, and is now continuing therapy being surgically NED. The other pt had a tumor progression after 9 mos from starting therapy and 6 mos from tumor response (with a negative PET scan). Treatment was relatively well tolerated, with skin toxicity in one pt. Conclusions: PDGFRA-D842V GIST are poorly responsive to TKI. We saw signs of antitumor activity in 3 pts with this mutation by combining TKI (imatinib or PKC412) with sirolimus. Tumor response was seen following some months of therapy. Studies are warranted. [Table: see text]
registHER: Treatment outcomes in patients with HER2-positive (HER2+), hormone receptor-positive (HR+) metastatic breast cancer (MBC)
Authors: Tripathy D. , Kaufman P. , Brufsky A. , Mayer M. , Yood M. , Wang L. , Brammer M. , Yardley D. , Tan-Chiu E. , Rugo H. 
Published: August 2020

1057 Background: Approximately 50% of HER2+ breast cancers are HR+ (defined as estrogen receptor [ER] and/or progesterone receptor [PR] positive). Cross talk between growth factor and ER-dependent signaling pathways may affect growth regulation in HER2+ breast cancers. Blockade of both pathways appears to be more active than blocking either alone based on randomized trials performed in selected populations. However, the outcomes of HER2+ and HR+ MBC patients relative to those in real- life clinical practice have not been evaluated in large cohort studies. Methods: registHER is a prospective observational study of 1023 patients with newly diagnosed (within 6 months [mo]) HER2+ MBC treated in community/academic settings, enrolled from 12/03 to 2/06. Median follow-up from MBC diagnosis was 25 mo at data cutoff (1/02/08). Treatment patterns and outcomes in patients with HER2+/HR+ MBC receiving 1st-line therapy (i.e., therapies received prior to 1st progression) are described in this analysis. Results: Of the 963 (94%) treated HER2+ patients with recorded HR tumor status, 55% (533) were HR+ and 45% (430) were HR-negative. 1st-line MBC treatment regimens for HER2+/HR+ patients included endocrine therapy (E) only, 57 (10.7%); E + trastuzumab (T), 50 (9.4%); chemotherapy (C) ± E, 41 (7.7%); and C + trastuzumab (T) ± E, 361 (67.7%). Progression-free survival (PFS) and overall survival (OS) by 1st line treatment groups are in the table. Conclusions: In registHER, HER2+/HR+ patients treated with E+T had longer PFS than patients treated with E alone; E- alone median PFS is consistent with findings in prospective randomized trials. These data provide further information regarding trastuzumab's role in targeting dual pathways in HER2+/HR+ MBC patients in a real-world setting. Multivariate analysis to address potential bias from known prognostic factors that may influence treatment choice will be presented. [Table: see text] [Table: see text]
Early results of a PMH Phase II Consortium trial of AZD0530 in advanced soft tissue sarcoma (STS)
Authors: von Mehren M. , Chu Q. , Alcindor T. , Townsley C. , Thallury S. , MacAlpine K. , Wright J. J. , Oza A. 
Published: August 2020

10579 Background: AZD0530 is a novel oral anilino quinazoline that is selective for c-Src, c-Yes, Lck, and Bcr-Abl through ATP competitive and reversible inhibition of the target enzyme. Src kinases play a role in tumor cell migration, invasion and metastasis as well as being part of the signaling cascade for angiogenesis and growth factors. Advanced STS have limited therapeutic options; therefore we tested the efficacy of AZD0530 in advanced STS. Methods: The study utilized a Simon Two stage design with the primary endpoint be objective tumor response + prolonged stable disease rate (defined as partial/complete response by RECIST, or stable disease >4 months). Patients with measurable advanced STS with up to one prior chemotherapy for metastatic disease were eligible for study participation following informed consent. Patients were excluded for cardiac dysfunction, poorly controlled hypertension, inability to swallow or absorb medication. Patients had pulmonary function tests at baseline that were repeated within the first 4 weeks of therapy. Results: 17 patients (11 F, 6M) with advanced STS (leiomyosarcoma 5, rhabdomyosarcoma 3, MFH/carcinosarcoma/Fibrosarcoma 2, endometrial stromal sarcoma/liposarcoma/non-rhabdoSTS 1 each) were enrolled, the majority of whom had prior therapy (14 chemo and 9 xrt). Five continue on study. Nine discontinued therapy for progressive disease, 2 for toxicity and 1 patient request. Median time to progression in the 13 patients was 1.7 months. Possibly related severe adverse events (all grade 3) included fatigue (2), anemia/lymphopenia/hypokalemia (1 each). To date no confirmed responses have been seen. No drug related pulmonary toxicity has been observed. Conclusions: AZD0530 can be administered safely as a single agent in patients with a variety of advanced STS. To date, tumor responses have not been noted; however patients were not selected based on tumor target expression. Further testing may be warranted in selected tumors in combination with chemotherapy given pre-clinical synergy data or in tumors pre-selected for target expression. No significant financial relationships to disclose.
Comparison of ER, PR, HER2 in primary and paired relapsed/metastatic lesions of metastatic breast cancer patients
Authors: Sari E. , Guler G. , Hayran M. , Altundag K. , Gullu I. , Ozisik Y. 
Published: August 2020

1063 Background: The assessment of ER, PR and HER2 is made routinely in every breast cancer patient to have information about prognosis and to select patients (pts) who are candidates for hormonal and anti-HER2 therapy. Recent studies have shown some degrees of discordance in ER, PR, and HER-2 expression between primary and recurrent/metastatic lesions (RML). In this study we compared the ER, PR, and HER2 status of the primary and paired RML in metastatic breast cancer pts. Methods: Analysis was made on 79 metastatic breast cancer pts whose ER, PR, and/or HER2 status were known both on the tissue samples of primary and RML. ER, PR, and HER2 status were determined by immunohistochemistry and/or fluorescence-in-situ hybridization. Results: Among the RML sites, 24% were locoregional, 76% were distant metastatic sites. Among 72 pts with known ER expression on both primary and RML, 36% showed discordance on ER expression. Most of the change occurred from negative to positive ER status (15 of 48 ER positive primaries had ER negative paired metastasis and 11 of 24 ER negative primaries had ER positive paired metastasis). Among 68 pts with known PR expression on both primary and RML, 51.5% showed discordance on PR expression. Change in PR status from positive to negative and negative to positive was similar (23 of 45 PR positive primaries had PR negative paired metastasis and 12 of 23 PR negative primaries had PR positive paired metastasis). Among 58 pts with known HER2 expression on both primary and RML, 15.5% showed discordance on HER2 expression. Six pts with HER-2 negative primaries, showed HER2 overexpression in their paired RML. Four pts who had HER2 overexpressing primary did not show HER2 expression in the paired RML. Conclusions: A proportion of pts show discordances in hormonal receptor and HER2 expression between the primary tumor and the paired RML. As these discordant results make changes in treatment decision, a biopsy of the metastatic lesion could be recommended in metastatic breast cancer pts when feasible. No significant financial relationships to disclose.
Brain metastases in breast cancer: Different survival by biological subtype and Ki67 expression
Authors: Sartori D. , Bari M. , Pappagallo G. L. , Rosetti F. , Olsen S. , Vinante O. 
Published: August 2020

1069 Background: Ten to 15% of patients (pts) with breast cancer will be diagnosed with central nervous system (CNS) metastases, and autopsy series suggest that up to 30% of pts have evidence of CNS disease at the time of death. The idenfication of factors that may predispose to CNS metastasis may help lead to earlier detection and possibly to improvement in disease management. Methods: Breast cancer pts with CNS metastases were identified within a database of 1300 breast cancer diganoses from 1995 to 2007 at the Department of Oncology, Azienda ULSS 13 VE. Pathologic features of tumor samples were examined using standard immunohistochemical assays. Results: Fifty-one pts with CNS metastases were identified. Median age at primary breast cancer diagnosis was 49 years (range, 28–78); median time to CNS metastases was 45 months (range, 3–244). HER2 overexpression was found in tumors from 25 pts (49.0%); 23 pts had tumors lacking overexpression of HER2, estrogen receptors (ER), and progesterone receptors (PgR) (ie, “triple negative” disease). Overexpression of p53 (at least 20% tumor cells positive), Ki67 (at least 20%), and BCL2 (at least 30%) were detected in tumors from 16 pts (31.4%), 32 pts (62.7%), and 14 pts (27.5%), respectively. Median survival from CNS involvement was 3.67 months (95% CI 2.05–5.28), with 24.4% and 15.3% of patients estimated to be alive at 12 and 24 months, respectively (Kaplan-Meier product limit method). A Cox proportional hazards analysis found that Ki67 overexpression was the only factor independently associated with a significantly increased risk of death (2.7-fold increase, p=0.028), while triple negative status was associated with a 1.8-fold increase in the risk of death (P=0.08) (Table). Conclusions: In our series of breast cancer pts with CNS metastases, nearly all had either HER2 overexpression or triple-negative disease. Pts whose tumors had higher proliferative indices, assessed by Ki67, had the poorest prognosis. [Table: see text] [Table: see text]
Differential timing and patterns of recurrence among breast cancer subtypes
Authors: Scruggs K. V. , Pradhan S. M. , Mfalila C. , Moore D. , Burrows E. , Drobish A. , Carey L. 
Published: August 2020

1076 Background: At present, effects of heterogeneity among breast cancer subtypes on timing and patterns of relapse are not fully understood. We characterized timing and patterns of distant recurrence among subtypes in women followed from initial diagnosis of breast cancer. Methods: 345 pts with newly diagnosed predominantly stage II-III breast cancer were treated with multiagent neoadjuvant therapy and subtyped by IHC: LumA (ER/PR+, HER2-); LumB (-ER/PR+, HER2+); Basal (triple neg); HER2 (HER2+,ER/PR-). Site-specific patterns of distant metastasis (DM) were examined among pts with single site of first DM. Sites of relapse were bone, CNS, viscera, lymph node, and soft tissue. Time to progression (TTP) was from date of initial diagnosis. Results: 108 patients developed metastatic disease; 65 demonstrated a single site of first DM. Basal subtype was associated with greater CNS and visceral metastases and fewer bone metastases than other subtypes. LumA subtype was associated with fewer CNS and greater bone metastases than other subtypes. [See table]. Dichotomizing as Basal v. non-Basal, bone v. no bone and CNS v. no CNS revealed identical trends with increased significance (p=0.01–0.03). TTP trended toward Basals demonstrating earliest DM and LumA latest. Excluding pts with DM at diagnosis, TTP differed between Basals and non-Basals within viscera (p=0.002, n=14/21, median TTP=10/21); CNS (p=0.047, n=8/7, median TTP=11/27); and bone (p=0.002, n=8/31, median TTP=9/21). Conclusions: Subtypes exhibit distinct timing and patterns of relapse within this largely homogeneous cohort of pts with predominantly locally advanced breast cancer, despite modern multiagent neoadjuvant therapy. Specifically, Basal cancers exhibit earlier recurrence and greater involvement of sites more difficult to treat than non-Basals. Within individual sites TTP differences between Basal and non-Basal tumors persist and are even more pronounced, suggesting that tumor microenvironment does not appear to be driving these differences. [Table: see text] No significant financial relationships to disclose.