bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-Hodgkin lymphoma in children: Is 1 g/m2 methotrexate as effective as 5 g/m2 in advanced-stage nonlymphoblastic non-Hodgkin lymphoma?
Authors: Kebudi Rejin , Zulfikar Bulent , Cakır F Betul , Gorgun Omer , Ayan Inci , Dogan Oner 
Published: March 2020

10043 Background: Survival rates in non-Hodgkin lymphoma (NHL) have increased significantly in the last decades. This study aims to assess the demographic data and treatment results of children with nonlymphoblastic NHL treated in a single institution. Methods: 106 children (74 male, 32 female), treated in Istanbul University, Oncology Institute, between 9/1989-12/2012 were evaluated retrospectively. Nonlymphoblastic NHL received COMP until 1991. After then, all received BFM protocols. They received BFM 90 protocol with 5 g/m2 methotrexate (MTX) until 1995 and modified BFM protocol with 1 g/m2 MTX thereafter. Results:The median age was 8(2-19) years. Histopathologic subtypes: 81 Burkitt, 25 large cell. The primary location was abdomen in 51, mediastinum 4, head/neck 31, 20 other (bone 8, breast 2, ovaries 2, skin 2, paravertebral 2, other 4). Bone marrow was involved in 10, CNS in 2. 40 patients had stage I+II, 44 stage III, and 22 stage IV disease. 23 patients died, 7 due to toxicity, 2 with second malignancies (AML,GBM). 10 year survival and EFS in the whole group was 76 and 76 % respectively. 10 year survival was 100, 94.3, 71.3 and 50% in stage I, II, III, and IV. In advanced stage nonlymphoblastic NHL patients, 10 year survival was significantly higher in patients receiving BFM regimen with 1 g/m2 MTX, than in ones receiving COMP or BFM protocol with 5 g/m2 MTX (10 year S, 81%, 46.7%, 44.4% respectively). These results were also compared with 47 advanced stage nonlymphoblastic NHL patients treated with 5 g/m2 BFM protocol in another center in the same university in the same time period (5 year S 78 %). Conclusions: Survival rates in the whole group are in parallel with advances attained in the world in NHL. The significantly higher survival rates achieved in patients with advanced stage non-lymphoblastic patients receiving modified BFM (1g/m2MTX) may be due to the decreased toxicity seen in this group and to the advances in supportive care in the last decade. In another major center in the same university that used the same protocol with 5 g/m2 MTX in the same time period, similar survival rates suggest that 1 g/m2 MTX which is cheaper and less toxic is also as effective as 5 gr/m2 in these patients.
Is magnetic resonance useful predicting neoadjuvant response in children with osteosarcoma?
Authors: Zapata-Tarres Marta , Castellanos-Toledo Araceli , Elizalde-Velazquez Susana , Deuña-Flores Armando , Peña-del-Castillo Humberto , Figueroa Carbajal Jose de Jesus 
Published: March 2020

10056 Background: Few prognostic factors had been described for pediatric high-grade osteosarcoma (HGO). Primary tumor necrosis percentage after neoadjuvant chemotherapy, analyzed by pathologists, remains as an important prognostic factor. Magnetic resonance imaging (MRI) has been postulated to predict necrosis in adults. Our aim was therefore to calculate the diagnostic utility of MRI in children. Methods: Prospective, longitudinal and clinical study was performed from September 2011 to January 2012. Twenty two patients (< 18 years), with extremity HGO and no prior chemotherapy treatment were included. All had MRI from diagnosis and just before surgery. We performed a sensibility-specificity analysis comparing percentage of necrosis by MRI vs histological Rosen grades (grades I and II were classified as bad responders; III and IV as good responders). Cut off value for MRI was 90%. Agreement between radiologists was calculated by Cohen´s Kappa coefficient. Results: Average age was 11.7 ± 3.04 (SD), 54.5% were women. All patients received neoadyuvant chemotherapy (cisplatin 120mg/m2 and adriamicin 75mg/m2). Nine patients had limb-sparing surgery, 8 limb disarticulation and 5 amputations; 72.8% were classified as bad responders by histology. MRI sensibility was 25%, specificity 86.6%, positive predictive value 50% and negative predictive value 68.4%. Kappa correlation coefficient between radiologists was 0,229. Conclusions: Diagnostic utility values in this study were lower than those reported previously. Torricelli, Dyke and Guo reported MRI sensibility of over 70% and specificity ranging from 37% to 87% (similar number of patients). Predictive values were also higher (> 80%). Differences are likely explained by the lack of correlation between radiologists. Our results support the need to establish systematized criteria to measure necrosis by MRI. In order to predict clinical response to chemotherapy in HGO, it is necessary to establish areas and cut off percentages of necrosis for appropriate clinical decision making.
Risk factors for underlying vitamin D deficiency in children with cancer at their diagnosis for cancer.
Authors: Tacyildiz Nurdan , Oktay Tanyildiz Gulsah , Yavuz Gulsan , Unal Emel , Dincaslan Handan , Gordu Zulfukar , Ozyoruk Derya , Oztuna Derya Gokmen , Biyikli Zeynep 
Published: March 2020

10068 Background: There is increasing interest in the possible association between cancer incidence and vitamin D. Our recent study showed a prominent Vit D deficiency in our pediatric cancer patients during their admition. Methods: Seventy newly diagnosed Pediatric cancer patients that have been defined as Vit D deficiency at our clinic, enrolled the study between 2010-2013. A questionare with 32 questiones has been performed to each patient’s family. Questiones are designed to determine risk factors for Vit D deficiency like; daily sun light exposure, consumption of food that known as source of the Vit D, suplementation during pregnancy, lactation and during infancy,etc.SPSS 11.5 program used for istatistical analyses Results: This study has been designed as a questionare based research to find out possible risk factors for Vit D deficiency in our patients. Seventy patients with leukemias , lymphomas and solid tumors were included in the study. Fourtysix boys (66%) and 24 girls ( 34%) were between 2 months to 18 years old (median: 9 years). Almost 60 % of the patients have been borned during autumn or winter. Education level : 8 % of the fathers and 19 % of the mothers were not received any education at school. During pregnancy 64% and during lactation 83% of the mothers have not been supplemented with Vit D. Seventy four percent of the mothers did not have any knowledge about importance of the Vit D. Supplementation of the Vit D during infancy was not avaliable for 58% of the patients. Daily exposure to the sun light was between 0 to 6 hours (median:2.2 hours/day). Monthly consumption of fish and egg was between 0 to 5 times (median: 1.3 time/month) for fish and between 0 to 45 eggs (median 13.9 eggs/ month ) respectively. Daily consumption of the milk was between 0 to 2 glases (median: 1 glass/day) . Conclusions: Famillies are not aware of the importance of Vit D. Consumption of Vit D containing foods are much lover than recomended nutrition facts.A special attention has to be given for education of parents for vit D supplementation during pregnancy, lactation and infancy. Besides, it should be started to educate peopele beginning from their childhood to have enough daily sun light exposure and Vit D containing foods as a part of their healthy life style.
The presence and extent of extracapsular extension (ECE) and the need for axillary lymph node dissection (ALND) in patients who meet ACOSOG Z11 eligibility criteria.
Authors: Dengel Lynn , Cody Hiram S. , King Tari A. , Van Zee Kimberly J. , Patil Sujata , Corben Adriana , El-Tamer Mahmoud , Stempel Michelle , Sclafani Lisa M. , Heerdt Alexandra S. , Gemignani Mary , Capko Deborah , Sacchini Virgilio , Plitas George , Morrow Monica 
Published: March 2020

1019 Background: Whether ECE mandates ALND in patients with ≤2 positive sentinel nodes (SN) is controversial. ACOSOG Z11 excluded patients with matted nodes, but did not comment on microscopic ECE. In a prospective, consecutive series of patients, we sought to determine if ECE correlates with the number of positive axillary lymph nodes (LN) and if ECE ≤2mm clinically differs from ECE >2mm. Methods: In 8/2010 an institutional treatment algorithm based on the Z11 results was prospectively applied to consecutive patients having BCS. ALND was performed for ≥3 +SNs. The approach to ECE was not specified. Characteristics of patients with and without ECE were compared with Fisher’s exact test and the Wilcoxon rank sum test. Results: From 8/10-11/12, 2157 invasive breast cancer patients had BCS; 381 had LN metastasis, 287 met Z11 selection criteria, and ALND was avoided in 242 (84%). ECE was present in 111 (39%), of whom 23% had ≥3 +SNs (vs 2% without ECE; p<0.0001) and 35% had ALND (vs 3% without ECE; p<0.0001). The presence of ECE was associated with tumor size (1.9cm vs 1.6; p=.01) but not with age, grade, or receptor status. The degree of ECE was associated with age, grade, number of +SNs, and performance of ALND (Table). In 45 cases, ALND was advised for ≥3 +SNs (n=29) or <3 +SNs with ECE (n=16). 39 patients had ALND and 34 of these had ECE. Additional +LNs were seen in 5/9 patients with ≤2mm ECE and 20/25 with >2mm ECE; median of 1 additional +LN in each group. Seven or more additional +LNs were seen in 6 patients with >2mm ECE; 1 patient with ≤2mm ECE had 6 additional +LNs, the remainder had ≤3. Conclusions: The presence of ECE was associated with ≥3 +SNs and the need for ALND. Only a minority of patients with ≤2mm of ECE had ≥3 +SNs, and nodal disease at ALND in this group was limited, suggesting that ≤2mm ECE may not be an indication for ALND. [Table: see text]
Predicting nonsentinel lymph node metastases using established nomograms among patients with breast cancer after primary systemic therapy (PST): The transSENTINA substudy.
Authors: Liedtke Cornelia , Goerlich Dennis , Van Zee Kimberly J. , Korndoerfer Jelka , Bauerfeind Ingo , Fehm Tanja N , Fleige Barbara , Helms Gisela , Lebeau Annette , Mai Marion , Staebler Annette , Von Minckwitz Gunter , Untch Michael , Kühn Thorsten 
Published: March 2020

1020 Background: Recent studies such as the SENTINA trial suggest that performing SLNB in patients with a cN1 status before but converting to a ycN0 status through PST result more often in a false-negative evaluation of LN status compared to SLNB at primary surgery. Therefore, there is a need to predict non-SLN status after PST and tailor axillary staging procedures. We investigated the accuracy of established nomograms to predict non-SLN metastases at primary surgery in patients after PST. Methods: The SENTINA trial is a 4-arm prospective multicenter cohort study evaluating an algorithm for the timing of a standardized SLNB in patients undergoing PST. 1,737 pts. from 104 institutions were categorized into four treatment arms according to the clinical axillary staging (including ultrasound examination) before and after chemotherapy. Patients in arm C with a cN1 status prior to PST converting to a ycN0 status but found to have a histologically positive SLN after PST were included. Several published nomograms predicting non-SLN status in patients with a positive SLN at primary surgery were applied (including the MSKCC-, Mayo-, Cambridge-, and Stanford-Nomogram, MDA-Score and Tenon-Score) and Area-under-the-Curve-(AUC)-values were calculated. Results:This subgroup comprised 592 patients. Among these, 74 patients had a positive SLN after PST and had all available data to run the nomograms. AUC-values were: MSKCC: 82.3 (95% confidence interval (95%CI) 72.6-91.9), Mayo: 71.8 (95%CI 60.1-83.5), Cambridge: 71.5 (95%CI 59.7-83.2), Stanford 70.6 (95%CI 59.7-83.2), MDA 70.7 (95%CI 59.0-82.5), and Tenon 73.1 (61.5-84.7). Conclusions: Analysis of the above nomograms in the post-neoadjuvant setting yielded AUC values comparable to those in the setting of primary surgery. Our results suggest that nomograms predicting non-SLN status in the setting of primary surgery (and particularly the MSKCC nomogram) may be used to avoid full axillary dissection in patients after PST.
A randomized controlled trial comparing zoledronic acid plus chemotherapy with chemotherapy alone as a neoadjuvant treatment in patients with HER2-negative primary breast cancer.
Authors: Horiguchi Jun , Hasegawa Yoshie , Miura Daishu , Ishikawa Takashi , Hayashi Mitsuhiro , Takao Shintaro , Kim Seung Jin , Tanino Hirokazu , Miyashita Masaru , Konishi Muneharu , Shigeoka Yasushi , Yamagami Kazuhiko , Akazawa Kohei , Kohno Norio 
Published: March 2020

1029 Background: Zoledronic acid (ZOL) has been found to have a synergistic anti-proliferative effect when used in combination with antitumor drugs. We investigated the synergistic effect of ZOL, assessed by pathological complete response (pCR) rate, when added to neoadjuvant chemotherapy (CT) in the primary tumor. Methods: Women with resectable invasive Stage IIA-IIIB breast cancer who are HER2-negative, between 20 and 70 years of age, and ECOG PS 0-1 were eligible. CT regimen was FEC100 q3w × 4 cycles followed by weekly paclitaxel for 12 cycles. ZOL 4mg was administered every 3-4 weeks, a total of 7 times. Patients were randomized 1:1 to the ZOL group or CT group, according to the presence or absence of lymph node metastasis, estrogen receptor (ER) status, and menopausal status. The primary endpoint was the rate of pCR defined as absence of invasive disease in the breast at surgery. The planned sample size was 180 patients. Results: 188 patients were recruited between March 2010 and April 2012; however 10 patients were excluded from the primary assessment. The overall pCR rate was 14.8% and 7.8% in the ZOL and CT groups, respectively (p=0.160). In the postmenopausal patients, pCR rate was 18.4% and 5.4% in the ZOL and CT groups, respectively (p=0.153). In the triple-negative patients, pCR rate was 35.3% and 11.8% in the ZOL and CT groups, respectively (p=0.225). In the postmenopausal and triple-negative patients, pCR rate was 50.0% and 0% in the ZOL and CT groups, respectively (p=0.077). There was no significant difference in severe toxicity between the two groups. Conclusions: The results of this trial suggest that the addition of ZOL to neoadjuvant CT has potential anti-cancer benefit in patients with postmenopausal and triple-negative breast cancer. Further investigation will be warranted. Clinical trial information: 000003261.
A retrospective comparison of the characteristics and recurrence outcome of triple-negative and triple-positive breast cancer.
Authors: Randhawa Jaskirat Singh , Alva Venur Vyshak , Kawsar Hameem , Spiro Timothy Peter , Haddad Abdo S. , Bagai Rajesh Kumar , Daw Hamed 
Published: March 2020

1038 Background: Triple-negative (estrogen/progesterone-receptors negative and HER2-negative; TNBC) and Triple-positive (estrogen/progesterone-receptors positive and HER2-positive; TPBC) breast cancers are very distinctive in terms of tumor behavior as well as disease management. Due to lack of an effective targeted therapy, the treatment options are limited for TNBC. We conducted a retrospective review to compare various characteristics and recurrence outcome in TNBC and TPBC. Methods: Over 3000 non-consecutive female breast cancer patients (diagnosed between 2000-2012) were reviewed. Of these, 406 patients (206 TNBC, 200 TPBC) were included. The following data at diagnosis were studied: age, tumor size, stage, grade, lymph node involvement, distant metastases and smoking history. Analyses are performed using R statistical software (Version 2.15.2). Numeric data are summarized by median and quartile with comparisons between groups performed by Wilcoxon Rank Sum Tests. Categorical data are summarized by frequency and percentage and comparisons between groups are performed by chi-square tests. Statistical significance is determined by a p-value ≤ 0.05. Results: Both TNBC and TPBC were diagnosed at similar median ages of 56.5 and 55 years respectively (p= 0.059). TNBC were more likely to have poorly differentiated histology (75.63%) whereas TPBC were more often moderately differentiated (54.79%) (p< 0.001). At diagnosis, Triple-Positive (TP) tumors were larger (median 2.4 cm) compared to Triple-Negative (TN) tumors (median 2 cm) (p= 0.013). However, there were no significant differences with respect to lymph node involvement and distant metastases in the two groups. Importantly, recurrences were more common in TNBC 33.85% (65/192) compared to TPBC 4.21% (8/190) (p < 0.001) and there was no association found with smoking history or active smoking status. Conclusions: TN tumors although smaller in size compared to TP were more likely to have poorly differentiated histology, showed higher recurrence rates and therefore were more aggressive in behavior. Both TNBC and TPBC were diagnosed at similar median age and exhibited no recurrence association with smoking history.
Use of adjuvant chemotherapy and outcomes in women age 70 and older with HER2-positive (HER2+) or triple-negative (TN) breast cancer (BC).
Authors: Hsu Tina , Speers Caroline , Tyldesley Scott , Chia Stephen K. L. 
Published: March 2020

1044 Background: Chemotherapy use decreases with increasing age. There is a stronger rationale for adjuvant chemotherapy in HER2+ and TN BC due to a higher risk of recurrence, known benefit of trastuzumab with chemotherapy and lack of other systemic options. Aims: 1) Characterize and compare outcomes of resected HER2+/TN BC in older women (age ≥70) (OW) vs. younger women (age 50-69) (YW) 2) Determine chemotherapy use in OW vs. YW 3) Compare outcomes in OW based on receipt of chemotherapy. Methods: Women ≥ 50 years old with newly diagnosed resected HER2+ or TN stage I-III BC in British Columbia between 2003 and 2006 were included. Demographic, prognostic and treatment characteristics were compared in OW vs. YW using Chi-Square and t-tests. Kaplan-Meier curves for relapse-free survival (RFS), breast cancer-specific survival (BCSS) and overall survival (OS) were calculated in the various cohorts. Results: OW (n=292) had larger tumors (p=0.002), more often had mastectomy and less often had adjuvant radiation (p<0.001) than YW (n=946). There were no differences in nodal or receptor status. OW vs. YW were less likely to receive chemotherapy (28.1 vs. 81.3%, p<0.001); odds decreased with increasing age (OR 15.9 and 7.4 for women age 50-59 and 60-69 vs. ≥70, p<0.001). OW had worse 5-year RFS (75.4 vs. 83.2%, p=0.002), local RFS (93.2 vs. 95.5%, p=0.05) and distant RFS (77.5 vs. 85.5%, p=0.001). Both 5-year BCSS (79.5 vs. 88.1%, p<0.001) and OS (63.7 vs. 85.8%, p<0.001) were worse in OW vs. YW. OS, but not BC-specific outcomes (RFS, BCSS), was significantly better in those who received chemotherapy compared to those who did not (Table). Conclusions: OW with HER2+ and TN BC are less likely to receive adjuvant chemotherapy than YW. No difference in BCSS was noted in OW based on receipt of chemotherapy, possibly due to a small sample size. Differences in OS based on receipt of adjuvant chemotherapy suggest that oncologists in British Columbia are accurately identifying women with limited life expectancy less likely to benefit from chemotherapy. [Table: see text]
Use of ponatinib to inhibit kinase mutations associated with drug-resistant gastrointestinal stromal tumors (GIST).
Authors: Heinrich Michael C. , Fletcher Jonathan A. , Anjum Rana , Serrano-Garcia Cesar , Vodala Sadanand , Bauer Sebastian , Town Ajia , Zhu Meijun , Ning Yaoyu , Eilers Grant , Griffith Diana , Patterson Janice , McKinley Arin , Wang Frank Y , Garner Andrew P , Rivera Victor M. 
Published: March 2020

10509 Background: Ponatinib (PO) is a multi-targeted tyrosine kinase inhibitor with potent pan-BCR-ABL activity that has recently been approved for treatment of CML and Ph+ ALL. PO also inhibits the kinase activity of KIT. Approximately 80% of gastrointestinal stromal tumors (GIST) contain primary activating KIT mutations, the majority of which cluster in exon 11. Imatinib (IM) is approved for the 1st line treatment of GIST; however, patients frequently relapse due to the acquisition of secondary resistance mutations located in either the KIT ATP-binding pocket or the activation (A) loop. Sunitinib (SU) is approved for 2nd line treatment of GIST but does not effectively inhibit A-loop mutants. Here we explored the activity of PO against major primary and secondary KIT mutants found in GIST. Methods: The drug sensitivity of KIT mutants was determined using engineered Ba/F3 cells harboring mutant forms of KIT exon 11 with or without ATP binding pocket or A-loop mutations. The abilities of PO, IM, SU, and regorafenib (RE) to inhibit viability and/or KIT kinase activity were compared using this system as well as an isogenic CHO cell system. We also profiled these same drugs using a panel of GIST cell lines, including cell lines with IM-resistant secondary KIT mutations. Results: In all in vitro systems, PO potently inhibited KIT exon 11 mutant kinases, with an IC50 of < 30 nM. PO also potently inhibited a range of secondary KIT mutants, including multiple A-loop mutant kinases. PO induced substantial tumor regression in Ba/F3 tumor models expressing a KIT exon 11 mutant with or without an A-loop mutation (D816H). Using GIST cell lines, PO inhibited the viability of those harboring primary KIT exon 11 and secondary resistance mutations more effectively than IM, SU, and RE. Importantly, in patients dosed once daily with 45 mg ponatinib, plasma concentrations achieved are predicted to lead to inhibition of all KIT mutants tested with the possible exception of V654A. Conclusions: PO potently inhibits the majority of clinically relevant KIT mutant kinases and has a broader spectrum of activity compared to IM, SU, or RE. Based on these data, a phase 2 study of PO in drug-resistant GIST is being initiated.