bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of gastrointestinal resection on sunitinib exposure in GIST patients.
Authors: de Wit Djoeke , van Erp Nielka P , Khosravan Reza , Wiltshire Robin , Allred Randy U. , Demetri George D. , Guchelaar Henk-jan , Gelderblom Hans 
Published: March 2020

10547 Background: GIST patients often have an altered anatomy of the GI tract due to either primary resection of the tumor or palliative surgery. It is unknown whether such GI resections affect the exposure to sunitinib and its active metabolite SU12662. Previous studies showed that the exposure to imatinib and nilotinib was decreased in GIST patients with prior major gastrectomy. Therefore, we postulated that GI resections might similarly affect sunitinib exposure. Methods: A retrospective analysis was performed to assess the effect of GI resections on sunitinib exposure. Pharmacokinetic data from 305 GIST patients included in 4 phase I-II trials were analyzed. Patients were subdivided into 6 groups according to prior GI surgery: 1)Major gastrectomy: 2)Partial gastrectomy: 3)Small bowel resection: 4)Combination of gastrectomy and small bowel resection: 5)Colon resection and 6)Controls with no prior GI surgery. Patients with uncertain GI resections were excluded. Dose normalized exposure (AUC0-24hr) of sunitinib and SU12662 was estimated with a population PK approach using NONMEM. Analysis of covariance was performed to test for significant differences in AUC between each of the subgroups and controls. Results: The geometric mean of total exposure to sunitinib and SU12662 was decreased by 21% and 28% in subgroup 4, (n=8; sunitinib: 931 ng*hr/mL (95%CI;676-1283) and SU12662: 354 ng*hr/mL (95%CI;174-720)) compared to controls (n=63; sunitinib: 1177 ng*hr/mL (95%CI;1097-1263) and SU12662: 491 ng*hr/mL (95%CI;435-555)), with the differences being significant (p<0.05) on the log scale. However, no significant differences in total exposures were observed between each of the other subgroups and control. Conclusions: In patients with a combined gastrectomy and small bowel resection, sunitinib and SU12662 exposure is significantly decreased as compared to subjects with no prior GI surgery. Contrary to previous results for imatinib, gastrectomy alone does not appear to influence sunitinib exposure. This should be taken into consideration for the treatment of GIST patients who had a gastrectomy. In theory, such patients might have better outcomes if treated with sunitinib, given the risk of subtherapeutic exposure to imatininb.
Patterns of toxicities and outcome in children versus adolescents/young adults (AYA) with metastatic rhabdomyosarcoma (RMS): A report from the Children’s Oncology Group (COG) Soft Tissue Sarcoma Committee.
Authors: Gupta Abha A. , Lyden Elizabeth , Anderson James Robert , Arndt Carola A. S. , Rodeberg David Anthony , Michalski Jeff M. , Parham David , Meyer William H. , Hawkins Douglas S. , Weigel Brenda 
Published: March 2020

10554 Background: Age at diagnosis is a prognostic factor in patients with RMS. We sought to determine whether AYA with metastatic alveolar (ARMS) or embryonal (ERMS) RMS had a different failure-free survival (FFS) compared to younger patients, and to identify treatment related factors that may be associated with outcome. Methods: COG ARST0431 patients were reviewed. The incidence of toxicities (AE, grade3/4 using CTCAEv3) by age was determined in 4 reporting periods (RP: wks 1-6; RP2:7-19; RP3: 20-34; RP4: 35-54). The AEs in younger patients (<=13 years) were compared with those in AYA. Fisher’s exact test was used to compare differences between the groups. Results: Of 109 patients, 60 (55%) were AYA. In RP1, they were more likely to have nausea/vomiting (4.1 vs. 16.9%, p=0.06), pain (6.1 vs. 20.3%, p=0.05), and metabolic disturbances (4.1 vs. 20.3%, p=0.02) compared to younger patients. In RP4, older patients trended to have less infection (15.8 vs. 30.1, p=0.07). All other toxicities were similar between the two age cohorts in the other RPs. AYA were less likely to complete therapy (52 vs. 73%, p=0.03) and more likely (in RP 4) to have unplanned dose modifications (outside of protocol guidelines) (23 vs. 2.7%). Of patients that completed therapy, there was no age-related difference in the time to completion. As shown in the table, younger patients had better 3-yr FFS, driven by a lower FFS for AYA with ARMS. Conclusions: This evaluation suggests that AYA with RMS were less likely to complete therapy and experienced a higher prevalence of pain and nausea compared to younger patients; the role of reporting bias and reasons for treatment discontinuation need further study. Children were more likely than AYA to have infection. Inferior FFS was only seen in AYA with ARMS suggesting a clear need for novel therapies for these patients. This study may be underpowered to demonstrate significant differences in other toxicities or in FFS among ERMS patients. [Table: see text]
Assessment of multimodality therapy use for extremity sarcoma in the United States.
Authors: Sherman Karen L. , Wayne Jeffrey D. , Agulnik Mark , Bentrem David J. , Bilimoria Karl Y. 
Published: March 2020

10559 Background: National guidelines for extremity sarcoma recommend multidisciplinary consultation, but treatment approaches are not standardized. Our objectives were to (1) examine trends in the multimodality treatment of extremity sarcoma in the US, (2) examine adjuvant therapy practice patterns, and (3) identify factors associated with the use and sequencing of adjuvant treatment. Methods: Using the National Cancer Data Base (2000-2009), use of multimodality treatment for non-metastatic extremity sarcoma was examined. Regression models were developed to identify factors associated with adjuvant therapy receipt and treatment sequence. Results: A total of 22,051 patients underwent resection (Stage I: 45%, stage II: 28%, Stage III: 27%). Trend analysis demonstrated relatively constant rates of radiation therapy (RT) (58% to 65%), chemotherapy (21% to 23%), and any adjuvant therapy (65% to 72%), however the proportion receiving neoadjuvant therapy increased (RT: 14% to 28%; chemotherapy: 9% to 13%; any: 18% to 27%; all p <0.001). Stage-specific treatment use is shown in the table below. Though RT rates were similar for all histologies, chemotherapy rates for synovial sarcoma were higher for all stages (I: 24.3%; II: 24.9%; III: 53.2%, p < 0.001). After adjusting for differences in tumor factors, patients were more likely to receive neoadjuvant therapy (chemotherapy and/or RT) if treated at high-volume academic center (p<0.001). After adjusting for histology, patients were more likely to receive adjuvant radiation therapy if younger, healthier, privately insured, or tumor size >5cm. Patients were more likely to receive adjuvant chemotherapy if were younger, healthier (fewer comorbidities), underinsured, treated at a high-volume academic center, or tumor size >5cm. Conclusions: Use of a multimodality approach for extremity sarcoma management has increased over time, particularly for neoadjuvant therapy. However, practice patterns are related to hospital type and socioeconomic factors. There may remain opportunities to increase multidisciplinary care and multimodality treatment for extremity sarcoma in the United States. [Table: see text]
Desmoid tumor (DT): Clinical and treatment characteristics and quality of life (QoL) in a large cohort from a referral center.
Authors: Ronellenfitsch Ulrich , Wiedemann Bea , Menge Franka , Jakob Jens , Hohenberger Ralph , Kasper Bernd , Hohenberger Peter 
Published: March 2020

10566 Background: Due to its low incidence, evidence regarding DT is scarce, and consensus on recommended treatment is difficult to achieve. This study systematically assesses clinical presentation, treatment characteristics and QoL in a large cohort of DT patients (pts). Methods: Demographic and clinical variables were retrieved from a database of 224 pts with histologically confirmed DT presenting to our referral center from 10/04-7/12. For a subset of 46 pts, QoL was assessed with the SF-12 questionnaire. The distribution of variables in the entire pt population and clinically relevant subgroups was calculated and compared with appropriate statistics (t-test, nonparametric tests). Denominators varied due to non-availability of variables for some pts. Results: 153 (68.3%) pts were female. Mean age at first diagnosis was 36.9 (3-73) yrs. Primary tumor site was limb/intraabdominal/rectus abdominis/trunk in 40/43/43/66 (21/22/22/35%) of 192 pts. 65/108 (60%) pts recalled a trauma or medical intervention at the DT site. 38/43 (88%) pts with rectus abdominis DT were female, and 31/38 (82%) had previous pregnancies, median time to DT diagnosis after end of pregnancy was 17 months. Primary therapy was resection/imatinib/tamoxifen/watchful waiting in 136/9/8/7 (83/6/5/4%) pts. Resection was R0/R1/R2 in 47/66/22 (35/49/16%) pts. After R0/R1 resection, DT recurred in 46% and 62% resp. after a median of 356/334 days. Physical/mental SF-12 summary scores were 39.2/40.8, 41.5/45.4, and 48.0/44.5 in pts with limb, intraabdominal, and trunk DT and 38.6/42.6 and 43.3/42.5 in pts with and without recurrence (reference population score 50; all p>0.05 for subgroup comparisons). Five women delivered a healthy child in parallel to clinically existent DT. 56% of our patients are alive with disease, whereas 44% have no evidence of disease. Conclusions: In 83% of DT pts, resection is the first treatment step and is R0 only in one third. 60% of the pts recall trauma/medical intervention at the DT site. Rectus abdominis DT occur after a median of 1.5 yrs after pregnancy. Despite the fact that 56% of our pts live with disease, their QoL is only slightly decreased, with lowest values for physical QoL in pts with recurrence.
Cetuximab in combination with docetaxel (T) in patients with operable, triple-negative breast cancer (TNBC): Preliminary results of a multicentre neoadjuvant pilot phase II study.
Authors: Nabholtz Jean Marc , Mouret-Reynier Marie-Ange , Van-Praagh Isabelle , Servent Véronique , Jacquin Jean-Philippe , Bourcier Anne-Véronique , Del Piano Francesco , Dubray-Longeras Pascale , Nayl Beatrice , Abrial Catherine , Kwiatkowski Fabrice , Dauplat Marie-Mélanie , Radosevic-Robin Nina , Cayre Anne , Uhrhammer Nancy , Bidet Yannick , Chalabi Nassera , Bignon Yves-Jean , Penault-Llorca Frederique , Chollet Philippe 
Published: March 2020

1057 Background: Cetuximab is an antiboby targeting the epidermal growth factor receptor (EGFR) to which a role has been suggested in TNBC. Therefore, we evaluated the combination of docetaxel with cetuximab as neoadjuvant therapy of operable TNBC. Methods: 35 patients with stage II-IIIA disease were prospectively included in this multicentre pilot study. Systemic therapy (ST) consisted of 6 cycles of T (100 mg/m2) q.3 weeks, in combination with weekly cetuximab (first dose : 400mg/m², then : 250 mg/m²/week) for 6 cycles. All patients underwent surgery at completion of ST. Complete pathologic response (pCR) was the primary endpoint (Sataloff : J Am Coll Surg 1995 ; Chevallier : Am J Clin Oncol 1993), with toxicity and biologic ancillary studies as secondary endpoints. Results: Patients characterisctics are as follows : mean age 48 [28-67] ; T1 : 3%, T2 : 73%, T3 : 24% (mean tumor size : 40 mm [15-100]) ; N0 : 61% and N1-N2 : 39%; invasive ductal carcinoma : 100%; Scarff-Bloom-Richardson Grade III : 73%, grade II : 27%. The median number of cycles was : T : 6 [1-6], cetuximab : 15 [1-18]. Pathological complete response was 24% according to Chevallier and Sataloff’s classifications and 28% if we consider response in breast. Preliminary results on 23 patients show an overall clinical response rate of 57% (22% CR). Conservative surgery was performed in 75% of cases. Skin toxicity was the main side-effect : grade II : 39%, grade III : 36%, grade IV : 3%. Neutropenia grade IV : 12.7%, febrile neutropenia : 1.3%, infection : 0%. Hand-foot syndrome grade III : 3%, grade II : 3%. Ungueal toxicity grade III : 3%, grade II : 33%. Conclusions: These preliminary results suggest that cetuximab in combination with Tappears to have a modest efficacy in operable TNBC. Clinical trial information: NCT00600249.
Synovial sarcoma: Is chemotaxis important to tumor progression?
Authors: Palmerini Emanuela , Benassi Maria Serena , Benini Stefania , Pazzaglia Laura , Staals Eric L. , Gamberi Gabriella , Gambarotti Marco , Picci Piero , Ferrari Stefano 
Published: March 2020

10571 Background: Synovial sarcoma (SS) is a rare and aggressive soft tissue tumor. In a first study (Palmerini E, Cancer 2009) we analyzed clinical prognostic factors in a retrospective series of 250 patients (pts) who were treated at Rizzoli Institute between 1976 and 2006. Stage, age, size, histology and use of radiotherapy influenced survival, whereas the role of chemotherapy was unproven. In the present study on the same patient population, in order to identify new prognostic factors and potential therapeutic targets, a panel of markers involved in chemotaxis and tumor growth were assessed. Methods: The expression of the chemokine receptor CXCR4 (a marker for chemotaxis which plays a critical roles in cancer progression) and the insulin-like growth factor receptor-1 (IGFR1) (a marker of growth activation ) were evaluated by IHC staining. Results: Tissue samples were available for the analysis in 88 patients (45 female and 43 male); median age was 37 years (range 11-63); size of the lesion was > 5 cm in 60 patients (71%); histology was biphasic in 30 (34%) of patients. All pts underwent surgery, 56% of pts underwent adjuvant radiotherapy (RT) and 68% adjuvant chemotherapy. With a median follow-up of 6 years (1-30 years), the 5-year overall survival (OS) was 70% (60-81). A positive stain for IGFR1 was detected in 55 pts (62.5%), with expression in the nucleus in 21 pts. CXCR4 was expressed in 74 pts (84%), nuclear pattern in 31 pts. No relation between IGFR1 and CXCR4 expression and clinical variables was found. The 5-year OS was 63% (95%CI 41-85%) for pts with positive IGFR1/nuclear expression and 73% (95%CI 61-85%) p = 0.05, in pts with negative IGFR1/nuclear staining. Similarly, the 5-year OS was 47% (95%CI 27-66%) in patients with positive CXCR4/nuclear expression and 86% (95%CI 76-96%), p = 0.003, in negative cases. In a multivariate analysis including age, histology, size and use of RT, nuclear expression of IGFR1 and CXCR4 were confirmed statistically significant independent factor for OS. Conclusions: The nuclear expression of CXCR4 or IGFR1 negatively influences the survival in patients with SS. Further studies addressing the role of CXCR4 as a potential target in this high risk subgroup of SS patients are needed.
Isolated limb perfusion for soft-tissue sarcoma and regional melanoma.
Authors: Derbel Olfa , Neidhardt Eve-Marie , Stoltz Adeline , Meeus Pierre , Dupre Aurelien , Combemale Patrick , Ray-Coquard Isabelle , Cassier Philippe Alexandre , de la Fouchardière Arnaud , Ranchere-Vince Dominique , Blay Jean-Yves 
Published: March 2020

10579 Background: Isolated limb perfusion (ILP) represents a treatment option for locally advanced melanoma and sarcoma confined to a limb. The advantage of this approach is to deliver high-dose regional chemotherapy without serious systemic effects. However, the ILP technique involves a complex and invasive operative procedure, requiring accurate monitoring to avoid major local toxicity. Methods: From November 2004 to December 2011, 58 patients underwent IPL for unresectable soft tissu sarcoma (STS= 34) and advanced in-transit melanoma (n=24). IPLs were performed at mild hyperthermic conditions with 1-2 mg of TNF and 40-80 mg of melphalan (M) for arm and leg perfusions, respectively. The response rate, disease free intervals, overall survival, toxicity and limb salvage rate were evaluated. Results: Median age was 68 years (range: 29-91 years), with 58% of women. For sarcoma patients, median tumor size was 60 mm, 16 patients (47%) had a high grade STS. Twenty-one patients (61%) received IPL before definitive surgery. Eight patients finally underwent amputation, giving a long-term limb salvage of 77%. The overall response rate was 73.5% (Complete response rate 14.7%, partial response rate 58.8 %). For melanoma patients, 9 (38%) had an AJCC stage III disease, the median thickness of the primary tumor was 3.5 mm. A complete response was obtained in 21% of patients while 54% exhibited a partial response. The local and metastatic recurrence rates were similar between sarcoma and melanoma patients (41% and 33% respectively). All but one of the patients with non-operated sarcoma presented a local or metastatic relapse.There was no mortality and no systemic toxicity. Regional toxicity (Wieberdink scale) was: grade I (no reaction) 53 %, II (erythema, oedema) 34%, III (blistering) 8% and IV 3%. The median local relapse-free survival was 40 months in sarcoma group (26.6 months for non operated patients) and 10 months in melanoma one. The overall 3-years survival rate was 44% for sarcoma and 25% for melanoma patients. Conclusions: ILP induces a high tumour response rate, leads to a high limb salvage rate but is associated with an important recurrence rate. It provides a limb salvage alternative to amputation when local control is necessary.
Response to the anti-EGFR antibody panitumumab combined with standard neoadjuvant chemotherapy in triple-negative breast cancer (TNBC): The immune and IGFR pathways.
Authors: Penault-Llorca Frederique , Dauplat Marie-Melanie , Abrial Catherine , Weber Beatrice E. , Mouret-Reynier Marie-Ange , Gligorov Joseph , Tredan Olivier , Privat Maud , Uhrhammer Nancy , Desrichard Alexis , Bidet Yannick , Radosevic-Robin Nina , Cayre Anne , Aubé Cécile , Romero Pierre Charles , Kwiatkowski Fabrice , Chalabi Nassera , Bignon Yves-Jean , Chollet Philippe , Nabholtz Jean-Marc 
Published: March 2020

1058 Background: EGFR overexpression is one of the hallmarks of the “basal-like” TNBC definition by immunohistochemistry (IHC). In a phase II neoadjuvant clinical trial targeting EGFR in TNBC, we investigated various biomarkers to better identify an EGFR-sensitive population for potential further regimen development. Methods: Sixty patients (pts) with stage II-IIIA TNBC were prospectively included. Systemic treatment (ST) consisted of the anti-EGFR antibody panitumumab combined with FEC 100, followed by 4 cycles of docetaxel. All pts underwent surgery after ST completion. Patient characteristics: median tumor size: 40 mm (20-120); invasive ductal carcinoma: 96.7%; SBR grade III: 71.7%; complete pathological response (pCR) rate: 55.3% and 46.8% (according to Sataloff’s and Chevallier’s classifications, respectively). Paraffin-embedded and frozen tumor samples were collected before and after ST for biologic studies. Germinal BRCA1 mutations, and EGFR, KRAS, BRAF and PI3KCA somatic mutations were analyzed by NGS. EGFR, IGF-1R, MET, cytokeratins 5/6 and 8/18, PTEN, P-cadherin, ALDH1, Ki-67, p53, tumoral FOXP3 expression and the number of FOXP3+ or CD8+ tumor-infiltrating lymphocytes (TILs) were evaluated by IHC. Results: High CD8+ TILs was response-predictive (p=3.4.10-6). Tumor FOXP3 expression and high FOXP3 TILs tended to be predictive. High IGF-1R expressors responded better than low expressors (p = 0.028). Comparison of EGFR, IGF-1R and Her3 in biopsies versus surgical samples showed reduced EGFR levels in non-responders (p = 0.037), while Her3 (p = 0.049) and IGF-1R (p = 0.08) increased. Sequencing revealed BRCA1 mutations in 10% of pts. No difference of response (pCR) was observed between mutated patients and others. Somatic mutations of PI3K were observed in 6 pts. No mutations were observed in BRAF, KRAS, or EGFR. Conclusions: The CD8+ TIL count seems to predict the response to panitumumab. Tumor FOXP3 expression and high FOXP3 TILs also tended to be predictive. Tumor levels of IGF-1R seem to play a determinant role in TNBC response to anti-EGFR antibodies, in concordance with our observations in a head-and-neck cancer cohort. Clinical trial information: NCT00933517.
A prospective multicenter phase II study of sunitinib in patients with advanced aggressive fibromatosis.
Authors: Jo Jae-Cheol , Hong Yong Sang , Kim Kyu-Pyo , Lee Jae-Lyun , Lee Jeeyun , Park Young Suk , Kim Sun Young , Ryu Jin-Sook , Lee Jong-Seok , Kim Tae Won 
Published: March 2020

10589 Background: There have been reports on responses and prolonged disease stabilizations with imatinib which may be associated with PDGFR-β pathway and KIT mutation in the treatment of aggressive fibromatosis (AF). Sunitinib has not only PDGFRs, KIT, and FLT3 inhibiting activity, but also VEGFRs blockade as antiangiogenesis. The aim of this study is to evaluate the efficacy and safety of sunitinib for patients with advanced AF. Methods: Nineteen patients with pathologically proven AF were accrued between Jun 2008 and Mar 2012. Sunitinib was administered with 37.5 mg/day for 4 weeks without break, comprising one cycle. Primary endpoint was response rate. Results: Ten (53%) patients were female and the median age was 30 years (range, 22-67). Most of the primary sites were intra-abdominal (12, 63.2%), and AF associated with familial adenomatous polyposis was observed in 10 (52.6%). With a median 6 cycles per patients (range, 1-47 cycles), 5 (26.3%) achieved a partial response and 8 (42.1%) had stable disease; the overall response rate was 26.3% (95% CI, 6.3-45.7) in intention-to-treat analysis. With median follow-up time of 20.3 months (range, 1.8-50.7), the 2-year progression-free survival and overall survival were 74.7% and 94.4%, respectively. Grade 3 or 4 adverse events of sunitinib with frequency > 5% of patients included neutropenia (33.3%), diarrhea (5.3%), and hand-foot syndrome (5.3%). In 3 patients out of 12 patients with mesenteric AF, mesenteric mass bleeding (n=1), bowel perforation (n=1), and bowel fistula (n=1) with tumor mass necrosis, were observed during an early period of sunitinib. Conclusions: Sunitinib showed potential antitumor activity and was relatively tolerated in patients with AF, especially non-mesenteric AF. Further investigation of sunitinib treatment is necessary in patients with AF.