tbuckley/cabot-search huggingface dataset:
Ovarian function suppression, symptom burden, and quality of life in young women with breast cancer: A prospective study.
Authors: Shoshana M. Rosenberg, Kathryn Jean Ruddy, Rulla M. Tamimi, Shari I. Gelber, Lidia Schapira, Virginia F. Borges, Steven E. Come, Meghan E Meyer, Eric P. Winer, Ann H. Partridge
Journal: Journal of Clinical Oncology (2015)

515 Background: Recent clinical trial data have demonstrated that ovarian function suppression (OS) in addition to tamoxifen (T) or aromatase inhibitors (AI) can improve breast cancer free survival in young women with hormone positive (HR+) breast cancer. We evaluated the impact of OS on quality of life (QOL) in young women, a population at risk for worse QOL outcomes and survival. Methods: Patient reported symptom and QOL data were collected 1 year after dx as part a cohort study enrolling women newly dx’d with breast cancer age ≤40. Severity of symptoms (Breast Cancer Prevention Trial checklist) was compared between women on OS+T vs. T alone by Fisher’s exact test. For QOL (Cancer Rehabilitation Evaluation System (CARES) physical, psychosocial, sexual subscales), differences in mean scores between groups were compared with t-tests. All were stratified by receipt of chemotherapy. Due to small numbers, women on AIs were excluded. Results: Of444 women with Stage 0-III, HR+ disease on T, 106 (24%) reported OS use. The Table details symptom prevalence (% at least moderately bothersome) by group. Among women who had chemo (n=333), women on OS had higher (p≤.05) mean CARES scores (worse QOL) on all 3 subscales. Mean scores for women who did not receive chemo (n=111) were not significantly different between groups. Conclusions: Young breast cancer survivors on endocrine therapy have a high symptom burden which should be considered in treatment decision making and survivorship care. Women on OS+T experience more vasomotor and (in those who received chemo) greater cognition issues, and poorer QOL in the early survivorship period compared to T alone. Early intervention to reduce symptom burden should be offered to young women to potentially improve QOL, enhance adherence and optimize survival. Chemo p No chemo p OS+T N (%) T N (%) OS +T N (%) T N (%) Hot flashes 45 (59) 99 (39) 0.002 23 (77) 24 (30) <0.0001 Night sweats 36 (47) 86 (33) 0.03 19 (63) 28 (35) 0.009 Vaginal dryness 27 (36) 71 (28) 0.20 10 (33) 13 (16) 0.06 Difficulty concentrating 32 (42) 69 (27) 0.02 5 (17) 17 (21) 0.79 Easily distracted 30 (39) 67 (26) 0.03 6 (20) 18 (22) - Weight gain 16 (21) 29 (11) 0.04 2 (7) 7 (9) - Unhappy with appearance 37 (49) 86 (34) 0.02 5 (17) 21 (26) 0.45
MicroRNA profiling analysis in a series of high-risk intestinal GISTs.
Authors: Silvia Calabuig, Javier Martin Broto, Dolors Sanchez-Izquierdo, Antonia Obrador, Luis Ortega, Antonio Casado Herraez, Claudia María Valverde, Ines de Torres, Andres Poveda, Aitziber Ugalde, Angeles Sala, Rafael Ramos, Luis Miguel Gonzalez de Sande, Ferran Losa, Nuria Lainez, Pablo Luna Fra, Josefina Cruz, Ricardo Cubedo, Jose Antonio Lopez-Guerrero
Journal: Journal of Clinical Oncology (2013)

10532 Background: Resected localized GISTs exhibit a wide range of biological behavior from low to high risk of recurrence. Risk categories (low, intermediate and high) are built from mitotic count, size and location. However, the molecular mechanism related to GIST relapse has not yet been fully clarified. The purpose of this study is to characterize miRNA expression profile in high risk GIST patients for both, recurred and not recurred, and detect those differentially expressed in these two subsets. Methods: Twelve cases of high risk intestinal GIST, 6 with relapse and 6 without relapse, were selected for this analysis. Sections were obtained for RNA extraction using the miRNeasy FFPE kit (Qiagen) and miRNA was hybridized to the GeneChip miRNA 3.0 Array (Affymetrix) including more than 1800 human miRNA. Normalization and statistical analysis were performed with Partek Genomic Suite 6.6 software by means of ANOVA test. Fold-change (FC) and p-values were applied to generate miRNA differentially expressed lists. Results: A subset of 85 miRNA were significantly deregulated (p&lt;0.05; FC=1.5) when comparing both groups. Among them, the highest p-values and associated FC were: mir-4776 (FC= 1,95, p= 0,011;), mir-1973 (FC= 1,59, p= 0,014) mir-4649 (FC 1,74, p= 0,028) and mir-3605 (GC= 1,58, p=0,045). All of these were up-regulated in recurred patients. Interestingly, the two samples that correspond to the biggest tumors with relapse showed a significantly different expression profile that separated them from the rest of the samples. We have identified 44 miRNAs that discriminate these two samples from the rest and show a very high statistical significance. The most significantly up regulated miRNAs were miR-100 (FC= 90,87, p&lt;0.0001), miR-30a (FC= 156,086, p&lt;0.0001) and down regulated miR-1184 (FC= -24,94, p&lt;0.0001) and miR-4529 (FC= -16,61, p&lt;0.0001). These miRNAs are involved in cell cycle and cell proliferation. Conclusions: This is the first wide characterization of miRNA profile in high risk GIST. The highest differences in expression are related to not previously described miRNAs in GIST tumors. All of them are involved in cell cycle and cell proliferation, thus expecting to regulate many GISTs associated genes, related to the relapse event.
The predictive role of consecutive measurements of serum CEA for treatment efficacy in advanced non-small cell lung cancer patients harboring epidermal growth factor receptor mutations treated with gefitinib or erlotinib.
Authors: Chi-Li Chung, Ling-Ling Chiang, Ming-Chih Yu, Sey-En Lin, Shih-Hsin Hsiao
Journal: Journal of Clinical Oncology (2013)

e19029 Background: Patients with non-small cell lung cancers (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations dramatically respond to EGFR tyrosine kinase inhibitors (TKIs) with approximately 70% response rate. Carcinoembryonic antigen (CEA) has been suggested to be associated with tumor recurrence, treatment efficacy and prognosis in some specific tumors. However, the role of CEA in NSCLC with EGFR mutations remains unclear. Therefore, we sought to elucidate whether the determination of serum CEA levels can predict the efficacy of EGFR TKIs in NSCLC harboring EGFR mutations. Methods: Medical records of 326 consecutive patients with advanced NSCLC between January 2007 and November 2012 were reviewed and a total of 104 patients with NSCLC harboring EGFR mutations treated with gefitinib or erlotinib ³2 weeks and with available data of serum CEA were identified for analysis. Results: Female, never smokers, adenocarcinoma histology and cases with pretreatment serum CEA ³ 5 ng/ml presented 63%, 76%, 96% and 68% of 104 eligible cases with mean age of 65.4 ± 13.7 years, respectively. The response rate of EGFR TKIs in patients with pretreatment CEA ³ 5 ng/ml was not significantly different (70% vs 91%, P = 0.339), and it was higher in those with reduction of CEA level after treatment than those without (94% vs 35%, RR=2.7, P &lt;0.001). The average change of pre- and post-treatment CEA in respondents and non-respondents was negative 112 ± 181 ng/ml and positive 368 ± 514 ng/ml, P &lt;0.001, respectively. In details, the pre- and post- treatment CEA levels in respondents were 246 and 71 ng/ml, P &lt; 0.001, respectively, and those in non-respondents were 157 and 268 ng/ml, P= 0.019, respectively. Furthermore, the post-treatment CEA level increased by 14% in non-respondents and decreased by 52% in respondents. Conclusions: Reduction or elevation of post-treatment serum CEA can predict the treatment efficacy in NSCLC patients with EGFR mutations treated with gefitinib or erlotinib. Further studies aiming to investigate the value of serum CEA levels in tumor progression and survival are warranted.
VOTRAGE study pazopanib in vulnerable elderly patients after geriatric assessment—A phase I study with geriatric criteria.
Authors: Loic Mourey, Alain Ravaud, Laurence Digue, Catherine Terret, Emmanuel Sevin, Thomas Filleron, Laurent Balardy
Journal: Journal of Clinical Oncology (2015)

TPS9635 Background: Efficacy and toxicity of targeted therapies don’t seem to vary considerably with age, but the impact of side effects in elderly patients is a major concern for clinicians. Our study aims to find the maximum tolerated dose (MTD) of Pazopanib (P) in a population of elderly patients, classified as “vulnerable” after comprehensive geriatric assessment (CGA), with a phase I methodology, integrating a geriatric criterion (2 points drop in ADL). Pharmacokinetic and pharmacogenomic studies are also planned. Methods: Open-label, multicenter (4), non-randomized, phase 1 dose escalation study to determine MTD and DLT (dose-limiting toxicity) of P in a population of vulnerable elderly patients, selected after CGA.Eligible patients will be enrolled into a standard 3+3 design with a dose of P of 400, 600 and 800 mg daily. DLT will be assessed during the first month. Patients will receive P until progression or untolerable toxicities (30 pts max). Main inclusion criteria: Age ≥ 75; metastatic cancer (kidney, lung, neuroendocrine pancreatic, sarcoma, ovary, thyroid, bladder, breast); No geriatric syndrome, no ADL impairment; Geriatric disorders (and/or); CIRSG: ≤2 gr 3 comorbidities; IADL: <8; SPPB: 6-9; MNA: 17-23; MMSE: < 24; GDS 15: >5 Geriatric assessment: G8 ADL: Activities Daily Living, IADL: Instrumental ADL MMSE: Mini-Mental State Examination SPPB: Short Physical Performance Battery MNA: Mini-Nutritional Assessment CAM: Confusion Assessment Method GDS-15: Geriatric Depression Scale CIRS-G: Cumulative Illness Rating Scale for Geriatrics DLT definition: The MTD is defined as the highest dose level for which 6 patients were treated with a maximum of one patient (~20%) presenting a DLT during the first month of treatment. DLT is defined as follow: -geriatric criteria: drop ≥2 points in ADL -classical hematologic and non hematologic criteria. Status of the study: 11 patients included (2nd cohort of 2ndlevel - 600 mg daily) Conclusions: This study is an attempt to adapt a phase I methodology to vulnerable elderly patients. The results will help clinicians to prescribe Pazopanib in this particular but numerous population, relying on geriatric assessment. Study funded by GSK Clinical trial information: NCT01642017.
Gene signature in plasma and tumor to predict irinotecan chemosensitivity in gastric cancer.
Authors: Jie Shen, Jia Wei, Yitao Ding, Xiaoping Qian, Lixia Yu, Zhengyun Zou, Wen xian Guan, Baorui Liu
Journal: Journal of Clinical Oncology (2015)

e15098 Background: Personalized chemotherapy based on molecular biomarkers can maximize efficiency and reduce adverse effects. We investigated and validated predictive biomarkers for irinotecan and developed a gene signature that is closely associated with chemosensitivity to irinotecan in gastric cancer patients. Methods: We examined gene expression of APTX, BRCA1, ERCC1, ISG15 and Topo1 in plasma and paired formalin-fixed paraffin-embedded gastric cancer tissues from 175 patients and evaluated the association between gene expression levels and in vitro sensitivity to irinotecan. We used multiple linear regression analysis to develop a gene-expression model to predict irinotecan sensitivity in gastric cancer and validated this model in vitro and vivo. Results: The plasma gene expression levels of APTX (P= 0.006) and BRCA1 (P= 0.019) were significantly lower in irinotecan-sensitive gastric cancer samples, while ISG15 (P< 0.001) and Topo1 (P= 0.001) were significantly higher. The tumor gene expression levels of APTX (P< 0.001), BRCA1 (P< 0.001) and ERCC1 (P< 0.001) were significantly lower in irinotecan-sensitive gastric cancer samples, while ISG15 (P= 0.047) and Topo1 (P= 0.002) were significantly higher. Based on those genes, plasma and tumor gene signature for irinotecan sensitivity prediction were established. The plasma gene signature (Index = 0.447-0.130×APTX-0.051×BRCA1–0.166×ERCC1+0.026×ISG15+0.110×Topo1) was significantly associated with irinotecan sensitivity (rho = 0.642, P< 0.001). The sensitivity and specificity for the prediction of irinotecan sensitivity reached 63% and 87%, respectively. The tumor gene signature (Index = 0.488-0.020×APTX+0.015×Topo1-0.011×BRCA1) was significantly associated with irinotecan sensitivity (rho = 0.71, P< 0.001). The sensitivity and specificity for the prediction of irinotecan sensitivity reached 73% and 86%, respectively. We also validated the gene signature model in another independent set of gastric cancer samples (65% vs. 22%, P< 0.001). Conclusions: The gene signatures established herein based plasma and tumor gene expression levels are closely associated with irinotecan sensitivity among patients with gastric cancer.
Long-term outcomes of preoperative chemotherapy with modified DCS therapy for highly advanced gastric cancer.
Authors: Atsushi Matsuki, Atsushi Nashimoto, Hiroshi Yabusaki, Masaki Aizawa
Journal: Journal of Clinical Oncology (2014)

e15044 Background: Among patients (pts) with advanced gastric cancer (AGC), the poor prognosis was exhibited and many pts died even after R0 resection. The aim of this study is to evaluate the preoperative chemotherapy with docetaxel, cisplatin and S-1 (modified DCS therapy) for treatment in highly AGC. Methods: A retrospective analysis was performed in 107 pts (Stage II/III/IV; 11/38/58, man/woman; 83/24, median age; 66-years) treated with preoperative modified DCS therapy in our hospital between 2009 and 2012. Eligibility criteria included clinical T4 and/or Stage III/IV AGC, a Performance status of 0-2 and no prior chemotherapy. The regimen consisted of docetaxel and cisplatin infusion (35mg/m2, days 1 and 15) and oral administration of S-1 (80mg/m2, days 1-14) every 4 weeks. Surgery was planned 3 to 4 weeks after the chemotherapy. Pathological response was graded according to the JGCA criteria. Almost all pts were treated with S-1 as postoperative adjuvant chemotherapy. Results: The median cycles was 2 (1-13). The incidence of grade 3/4 toxicity was neutropenia 53.3%, anemia 10.3%, anorexia 11.2%, nausea 4.7%, and diarrhea 2.8%. All of these toxicities were well tolerable and there was no TRD. According to RECIST, The overall response rate was 74.8%. Ninety-two pts underwent gastrectomy (R0/R1/R2; 72/10/10), respectively. Postoperative morbidity rate was 20.7% and there was no mortality rate. Over all 5 years survival rate (5YSR) was 36.4 % and that of R0 was 52.5%, on the other hand 5YSR and MST of chemotherapy alone was 0% and 14.5 month. Pathological response rate (>=1b) was 67.4% and complete response was achieved 8 pts (8.7%). 5YSR of pathological responders who underwent R0 resection was 74.2% and that of non-responders who underwent even R0 resection was 25.5% (P<0.05). Conclusions: Preoperative modified DCS therapy for AGC was tolerable, and survival benefit of pathological responders with R0 surgery was promising and warrants further investigation.
Quantitative Total Bone Imaging in Patients with Metastatic Castration-Resistant Prostate Cancer Using NaF PET/CT.
Authors: Glenn Liu, Scott Perlman, Tim Perk, Stephanie Harmon, Mary Jane Staab, Robert Jeraj
Journal: Journal of Clinical Oncology (2015)

e16016 Background: Advanced prostate cancer is associated with the development of osseous metastases. There are no current tools that allow assessment of treatment response in bone. Methods: Quantitative Total Bone Imaging (QTBI) is an innovative tool that allows extraction of comprehensive functional information in all osseous metastases, as well as treatment response in individual lesions, using 18F-Sodium Fluoride (NaF) PET/CT. We completed a multi-center trial within the PCF Imaging Consortium assessing the performance characteristics (test-retest) and responsiveness of QTBI as an imaging biomarker of treatment response in men with metastatic CRPC to bone treated with either a taxane-based or androgen-signaling pathway directed therapy. Results: 54 patients have been enrolled from three academic centers. Imaging biomarkers of treatment response correlating with clinical outcomes (e.g. PSA response, PFS) have been identified for additional validation. Here we present data regarding the inter-lesional response heterogeneity and implications on patient care and drug development strategies. Conclusions: Changes in SUVmax, SUVtotal, and SUVmean reflect quantifiable PET measurements that are complementary. Relying on one measure alone can be misleading, particularly when assessing treatment response. For example, some lesions experience a decrease in SUVmax, while simultaneously having an increase in SUVtotal. This implies that the therapy decreased the max functional activity of the lesion, but the overall functional burden of the lesion increased analogous to “slowing down” progression. This is in contrast with some lesions that decrease (increase) in both SUVmax and SUVtotal, which would imply decreased activity and burden (increased activity and burden). We will show data representative of the above along with clinical outcomes in support of this conclusion, as well as the implications of treatment response heterogeneity. In summary, QTBI provides a unique tool in understanding the dynamics of treatment response, allowing newer trial designs that can explore combination, sequence, and the issue of continuing treatment beyond progression. Clinical trial information: NCT01516866.
Management of breast cancer associated with pregnancy.
Authors: Catherine Renee Lewis, Alysia Robertson, Fengxia Yan, Omar Danner, Derrick Beech
Journal: Journal of Clinical Oncology (2013)

e12573 Background: Pregnancy-associated breast cancer (PABC) continues to be a challenging problem and may be increasing in frequency as women delay childbearing. As of yet, there is no absolute consensus on the management of PABC. Methods: In order to determine the ideal management for breast cancer during pregnancy, a comprehensive chart review of all women diagnosed with breast cancer during pregnancy from 1995-2010, at a large, urban hospital was performed. We reviewed the medical records of over 2000 patients and identified 15 individuals with PABC. A literature review and retrospective analysis of treatment modalities used for patients diagnosed with breast cancer during pregnancy or during the immediate postpartum period were performed. Trimester of pregnancy, stage at diagnosis, nodal status and age were compared amongst pregnant and non-pregnant patients. The study was approved by our institutional review board. Results: Preliminary results indicated that there was an even distribution between stages of breast cancer at diagnosis among our patient population. Over 80% of the patients had infiltrating ductal carcinoma. Of the patients diagnosed during the first or second trimester, the majority underwent breast conservation therapy (BCT) with subsequent chemotherapy and/or radiation after delivery. Several patients underwent elected to terminate their pregnancy and received chemotherapy either during pregnancy or after termination. Conclusions: Our analysis shows that BCT is the most common treatment strategy for PABC at our institution, which is consistent with current literature. BCT appears to be safe and well tolerated in patients with PABC. Infiltrating ductal breast cancer is the most common type of malignancy in this subpopulation. A multi-disciplinary approach involving obstetricians, medical oncologists, radiation oncologists and surgical oncologists is needed to provide optimal care to these patients.
Health-related quality of life assessment in EORTC cancer clinical trials.
Authors: Efstathios Zikos, Corneel Coens, Divine Ewane Ediebah, Chantal Quinten, Eva Greimel, Henning Flechtner, Martin J. B. Taphoorn, Jaap Reijneveld, Michael Koller, Andrew Bottomley
Journal: Journal of Clinical Oncology (2012)

6090 Background: Over the last three decades health-related quality of life (HRQOL) has become an important part of the randomised controlled trials (RCTs) conducted by the European Organisation for Research and Treatment of Cancer (EORTC). This review aims to undertake a descriptive database evaluation of all the HRQOL studies conducted in EORTC since 1980. Methods: The EORTC protocol database (n=785) was reviewed, restricting the search to between 1980 and 2011 (n=735). We investigated the number of HRQOL studies conducted in EORTC trials, the RCTs’ status and the use of HRQOL tools since 1980. Results: 157 protocols with HRQOL assessment were identified involving 70,903 patients. 73 studies ended as defined in the protocol; 27 studies closed early due to poor accrual; 17 are at the final analysis of the primary end point stage; 14 studies are still open to recruitment; 11 are closed to patient entry; and 15 new RCTs are pending activation with HRQOL. The majority of phase III (n=135) and phase II/III (n=9) RCTs have HRQOL as secondary endpoint. EORTC also conducted a number of large scale field studies (n=11), where HRQOL was the primary endpoint. During the early period of 1980 to 1989 HRQOL was assessed in 12 EORTC RCTs by using a small number of HRQOL items, but from 1990 to 2000, HRQOL was assessed in 97 RCTs using more comprehensive HRQOL tools. Between 2001 and 2011 the number of RCTs with HRQOL was 48. The EORTC clinical groups with the most RCTs containing HRQOL were Radiation Oncology (n=22), Genito-Urinary (n=20), Gynaecological (n=16), Breast Cancer (n=16), Lung (n=13), Gastrointestinal, (n=13) and Brain (n=10). The EORTC HRQOL tools were used in 90% of the trials, with other validated tools being used when required. Conclusions: Our review of EORTC RCTs has shown how patient perspective has been constantly considered of major importance in oncology during the last three decades. The inclusion of patient perspective in drug development shows that a more comprehensive HRQOL assessment has taken place over time as better instruments have become available. As the positive value of patient perspective grows to clinicians, regulatory bodies and industry, we expect that EORTC will continue its support by including HRQOL endpoints where appropriate.