tbuckley/cabot-search huggingface dataset:
Updated survival analysis of patients (pts) with unresectable (UR) or borderline resectable (BR) locally advanced pancreatic adenocarcinoma (LAPC) treated with neoadjuvant FOLFIRINOX.
Authors: Moh'd M. Khushman, Peter Joel Hosein, Michel Velez, Lauren Carcas, Daniel Joseph Dammrich, Jorge Hurtado-Cordovi, Ritesh Parajuli, Terri Pollack, Jessica Macintyre, Ana Paula P. Harwood, Arturo Loaiza-Bonilla, Ikechukwu Immanuel Akunyili, Maria H. Restrepo, Jaime R. Merchan, Govindarajan Narayanan, Lorraine Portelance, Danny Sleeman, Joe U Levi, Caio Max S. Rocha Lima
Journal: Journal of Clinical Oncology (2014)

e15197 Background: Although no prospective data are available for the use of FOLFIRINOX in LAPC, in a retrospective study of 18 pts with UR or BR LAPC, neoadjuvant therapy with FOLFIRINOX with or without subsequent chemoradiation (CCRT) resulted in an R0 resection rate of 44% (Hosein et al, BMC Cancer 2012). In order to confirm these preliminary results, we analyzed a larger cohort of pts treated in a similar fashion with mature follow-up. Methods: We included consecutive pts from 2 centers with LAPC treated with first-line FOLFIRINOX with neoadjuvant intent. Pts were categorized as BR or UR using the NCCN criteria. Pts received FOLFIRINOX chemotherapy (at the full dose as described in the ACCORD-11 trial) until maximum response or tolerability, and then underwent surgery if their imaging suggested resectability. Pts then received CCRT if they were still UR or BR after FOLFIRINOX. The end points of this retrospective analysis were overall survival (OS), progression free survival (PFS), and R0 resection rate. Results: Between 2008 and 2013, 51 pts were included; 11 were BR and 40 were UR. The median age was 60 years (range 41–75), and all had an ECOG PS of 0 (20%) or 1 (80%). Most pts (63%) had pancreatic head tumors and 49% had biliary stents before therapy. A total of 429 cycles were given with a median of 8 (range 2–29); 27 (53%) went on to receive CCRT. Toxicities were similar to our previous report. After a median follow-up of 17 mo (range 2–56), the Kaplan-Meier median OS was 35 mo (95% CI 26–45), the 3-yr OS rate was 42% and the median PFS was 14 mo (95% CI 11–16). By imaging criteria, 13 (26%) were converted to resectability and 10 (4 BR and 6 UR) of these had successful R0 resections. Pts who had R0 resections had a significantly longer survival than pts who did not (3-yr OS rate 67% vs 21%, log rank p = 0.042). Conclusions: In this large retrospective study limited to pts with LAPC treated uniformly, the R0 resection rate with FOLFIRINOX was only 20%, but most of these pts were UR at baseline by NCCN criteria. The median OS of almost 3 yrs compares favorably to historical survival rates for LAPC pts. Prospective controlled trials testing this algorithm in LAPC are ongoing.
Identification of knowledge translation opportunities in the treatment of locally advanced breast cancer: Results of a national survey of physicians.
Authors: Yanchini Rajmohan, Robyn Leonard, Sophie Hogeveen, Jalal Ebrahim, Dolly Han, Audrey Wong, Jean-Francois Boileau, Sonal Gandhi, Justin Lee, Robert Edward Dinniwell, Muriel Brackstone, Christine E. Simmons
Journal: Journal of Clinical Oncology (2013)

6585 Background: Locally advanced breast cancer (LABC) accounts for only 10% of all breast cancers. While several guidelines and consensus statements exist, whether the current practice reflects these guidelines is unclear. We sought to survey the oncologists in Canada to assess current practice patterns and identify areas of targeted knowledge translation interventions (KTIs) in the treatment of LABC. Methods: 426 Canadian oncologists were surveyed with a 29 item survey-tool. They were subdivided into LABC experts (n=83) and non-experts (n=343). Physicians were removed from the survey if they identified that they were not involved in the treatment of breast cancer. The survey included demographic information as well as questions as to the current practice patterns utilized in the pathway of care for LABC patients. Level of discordance was calculated between the expert and non-expert responses using a z test. Results: 139 responses were obtained (48% response rate) from the non-experts and 51 responses were obtained from the experts (61% response rate). Areas of discordance in expert and non-expert survey included: frequency of clinical assessment during neoadjuvant therapy, methods for clinical assessment, radiographic re-evaluation post therapy, and assessment of receptor status (see Table). Conclusions: Several areas have been identified as targets for KTIs that may help to improve the quality and consistency of care of patients with LABC in Canada and may also have implications for improvements in resource utilization. [Table: see text]
5-year patient-reported outcomes of bowel and urinary bother in the CHHiP trial (CRUK/06/016).
Authors: David P. Dearnaley, Helen Mossop, Isabel Syndikus, Vincent Khoo, DJ Bloomfield, Chris C. Parker, John Logue, Christopher D Scrase, Alison J. Birtle, John Staffurth, Zafar Malik, Miguel Panades, Chinnamani Eswar, John Graham, J. Martin Russell, Annie Gao, Anna Wilkins, Clare Cruickshank, Clare Griffin, Emma Hall
Journal: Journal of Clinical Oncology (2017)

23 Background: Hypofractionated radiotherapy (hRT) has been shown to be non-inferior to conventional fractionation (cRT) in the CHHiP trial. Clinician reported toxicity was low across all fractionation schedules at 5 years (y), as were patient reported outcomes (PRO) to 2y. Here we aim to confirm these findings with PRO data at 5y. Methods: The CHHiP trial randomised patients (pts) in a 1:1:1 ratio to cRT: 74Gy/37 fractions (f) or hRT: 60Gy/20f or 57Gy/19f. Overall bowel bother (BB) and urinary bother (UB) were assessed as single items of the UCLA-PCI and EPIC-50 instruments. PRO were completed before hormone therapy and RT (pRT). Late symptoms were assessed 6 monthly from 6-24 months and yearly to 5y. Differences in the distribution of scores were assessed using a chi2 trend test. Odds of an increase in bother were modelled using ordered logistic regression. Kaplan-Meier methods were used to estimate time to “small” or worse bother, with RT schedules compared using the log-rank test. Results: Between Oct, 2002 and Nov, 2009 2100 pts were recruited into the PRO sub-study (696 74Gy, 698 60Gy and 706 57Gy). Return rates at 5y were 355 (51%), 388 (56%) and 402 (57%) for the 74, 60 and 57Gy schedules respectively. Cross-sectional analyses at 5y showed no difference between groups (Table 1). The odds of an increase in BB from pRT to 5y for hRT compared to cRT were (Odds Ratio (OR) (99% CI), p-value): 60Gy: 0.78 (0.52-1.18), 0.12; 57Gy: 0.75 (0.50-1.12), 0.06, and for UB were: 60Gy: 1.00 (0.67-1.50), 1.00; 57Gy: 1.08 (0.72-1.61), 0.62. Time to first late “small” or worse BB was also similar across groups (Hazard ratio (HR) (99% CI), p-value): 60Gy: 1.08 (0.85-1.37), 0.42; 57Gy: 0.92 (0.71-1.18), 0.36 or UB: 60Gy: 0.93 (0.73-1.20), 0.48; 57Gy: 0.91 (0.71, 1.17), 0.34. Conclusions: After 5 years follow-up, cRT and hRT showed a similar low level of patient reported BB and UB. Clinical trial information: ISRCTN97182923. [Table: see text]
Multispecialty care among hepatocellular carcinoma patients in SEER-Medicare.
Authors: Ian Michael Breunig, Fadia T. Shaya, C. Daniel Mullins, Viktor Chirikov, Brian S. Seal, Nader Hanna
Journal: Journal of Clinical Oncology (2012)

e14638 Background: Multispecialty care has increased for many cancers yet little evidence exists for hepatocellular carcinoma (HCC). Methods: Medicare non-transplant patients with HCC 1ry diagnosis in 2000-07 were studied using SEER-Medicare data with HCC claims generated from Medicare parts A-B, including patients with &gt;=1 claims for HCC-related physician visits post-diagnosis. Physician specialties were grouped as Gastroenterology (GE), General/Family/Geriatric/Internal (GF), Diagnostic/Intervention radiology (DIR), Hematology/Medical oncology (HMO), General surgery/Surgery oncology (GSO), Radiation oncology (RO), Multispecialty clinic/group practice (MG), or Others. Visits by specialty seen within 4 weeks, and trends, were explored by comparing distributions, using t-tests, of visits by specialty, from the 2000/01 diagnosis cohort and the 2006/07 cohort. Results: Out of 2284 HCC patients diagnosed in 2000/01, 1380 (60%) had at least one HCC-related physician visit post-diagnosis, and 1330 (58%) within 4 weeks. Excluding the “Others” category, 1015 (44%) visited within 4 weeks. Of 3155 patients diagnosed in 2006/07, 1782 (56%) had any HCC-related visit, 1689 (54%) within 4 weeks, and 1295 (41%) when excluding Others. Among patients with at least one post-diagnosis HCC-related visit ever, the percentage of patients who saw only 1 type of specialist within 4 weeks of diagnosis did not change (44% in 2000/01 vs. 43% in 2006/07; p=0.15); nor did the percentage visiting multiple specialists (52% vs. 53%; p=0.58). The percentage of patients visiting GE within 4 weeks went from 27% to 25% (p=.10), 11% to 10% (p=.41) for GF, 28% to 31% (p=.08) for HMO, 4% to 3% (p=.53) for RO, 65% to 67% (p=.33) for Others, and remained at 23% for DIR, 16% for GSO, and 1% for MG. Among patients who saw only 1 type of specialist within 4 weeks of diagnosis, the percentage visiting GE went from 14% to 12% (p=.29), 4% to 5% (p=.50) for GF, 11% to 10% (p=.55) for DIR, 11% to 12% (p=.36) for HMO, 4% to 3% for RO, 52% to 53% for Others, and remained at 5% for GSO, and &lt;1% for MG. Results are robust when “Others” are excluded. Conclusions: Despite increased incidence of HCC since 2000, there was no significant trend toward multidisciplinary care.
Influence of chemotherapy on the SPARC expression in gastric cancer.
Authors: Dingzhi Huang, Yongyin Gao, Rubing Han, Xia Wang, Shaohua Ge, Hongli Li, Ting Deng, Rui Liu, Ming Bai, Zhou Likun, Yi Ba
Journal: Journal of Clinical Oncology (2015)

e15087 Background: The expression of tumor biomarkers may change after chemotherapy. However, whether secreted protein, acidic and rich in cysteine (SPARC) expression changes after chemotherapy in gastric cancer (GC) is unclear. We investigated the influence of chemotherapy on SPARC expression in GC. Methods: Immunohistochemistry was used to analyze SPARC expression in 132 GC cases (including 54 cases with preoperative chemotherapy and 78 cases without preoperative chemotherapy). We assessed SPARC expression of postoperative specimens with and without preoperative chemotherapy to analyze the influence of chemotherapy on SPARC expression. Results: SPARC was highly expressed in GC compared with the desmoplastic stroma surrounding tumor cells and noncancerous tissues. High SPARC expression correlated with invasion depth, lymph node, and TNM stage. After chemotherapy, a lower proportion of high SPARC expression was observed in patients with preoperative chemotherapy than in the controls. For 54 patients with preoperative chemotherapy, gross type, histology, depth of invasion, lymph node, TNM stage, and SPARC expression were related to overall survival. Further multivariate analysis showed that lymph node, histology, and SPARC expression after chemotherapy were independent prognostic factors. Conclusions: SPARC expression may change after chemotherapy in GC. SPARC expression should be reassessed for patients with GC after chemotherapy.
Preclinical evaluation of selective inhibitors of nuclear export (SINE) in basal-like breast cancer (BLBC).
Authors: Dilara McCauley, Yosef Landesman, William Senapedis, Trinayan Kashyap, Jean-Richard Saint-Martin, Louis Plamondon, Vincent Sandanayaka, Sharon Shechter, Doriana Froim, Raphael Nir, Jennifer Williams, Lynda Chin, Cyril Benes, Mansoor Raza Mirza, Michael Kauffman, Sharon Shacham
Journal: Journal of Clinical Oncology (2012)

1055 Background: Basal-like breast cancers (BLBC) compose up to 15% of breast cancer (BC) and are usually triple negative characterized by lack of ER, PR, and HER-2 amplification. In addition, most BRCA1-associated BCs are BLBC and TNBC, expressing basal cytokeratins and EGFR. BLBC is characterized by an aggressive phenotype, high histological grade, and poor clinical outcomes: high recurrence and metastasis rates. CRM1 (XPO1) is the exclusive nuclear exporter of multiple Tumor Suppressor Proteins (TSP) including p53, p21, BRCA1&amp;2, pRB, FOXO. CRM1 inhibition forces nuclear accumulation of TSPs, inducing apoptosis in cancer cells. KPT-SINE are novel, small molecule, irreversible inhibitors of CRM1 with potent anti cancer activity. Methods: The Cancer Genome Atlas (TCGA) and BC cell line databases were used for mRNA analyses. MTT assay was used to determine the cytotoxic effect of KPT-SINE (KPT-185 and KPT-330) on 44 breast cell lines including luminal A, luminal B, HER2 positive, BLBC and TNBC cells. The effect of KPT-330 treatment on tumor growth was tested in vivo in the TNBC model MDA-MB-468 xenograft. Results: Analyses of nuclear pore complex (NPC)-related mRNA levels (including CRM1) showed clear separation of BCs into high and low NPC expression. BLBC subtype was enriched with high NPC transcripts while luminal BC was enriched in low NPC levels (p&lt;1.53e-20). High NPC levels had higher mutation levels in BRCA2 (cor=0.33, p=1.83e-8) and ABL1. NPC expression was inversely correlated with ER mRNA expression (cor=-0.58, p=1.37e-7). KPT-SINE showed potent cytotoxicity on &gt;75% of the cell lines (IC 50 values &lt;1 μM). Only three of 24 TNBC cell lines displayed IC 50 values &gt;1.5 μM upon KPT-SINE treatment. Genomic analyses on all BC lines indicated that p53, PI3K/AKT and BRCA1 or 2 status did not affect cytotoxicity. In MDA-MB-468 xenograft, KPT-330 displayed efficacy in a dose-dependent manner inhibiting nearly 100% of tumor growth compared with vehicle treated animals, and was well tolerated. Conclusions: These data show that NPC/CRM1 mRNAs are overexpressed in BLBC/TNBC and that CRM-1 mediated nuclear export inhibition by SINE represents a potentially novel and well tolerated therapy for BLBC / TNBC.
Identification of head and neck cancers (SCCHN) that may respond to dual inhibition of EGFR and HER3 signaling.
Authors: David S. Shames, Howard Stern, Kim Walter, Brittany Jiang, Ling Fu, An Do, Rajiv Raja, Tim Wilson, Jeff Settleman, Mark X. Sliwkowski, Andrea Pirzkall, Lukas C. Amler
Journal: Journal of Clinical Oncology (2012)

5575 Background: Oncogenic signaling through the epidermal growth factor receptor family is one of the most frequent alterations found in human epithelial cancers. These receptor tyrosine kinases mediate their effects via high-level co-expression and homo- and heterodimerization events that drive tumor growth, metastasis, and survival. Extensive preclinical studies suggested that some cell lines depend on oncogenic autocrine signaling through HER3 (Wilson et al.). This phenotype was particularly prominent in cell lines derived from SCCHN and was strongly correlated with high HRG expression. Interestingly, two patients with SCCHN tumors that expressed high levels of HRG in our phase Ia trial (abstract #95245) of MEHD7954A, a dual-action human IgG1 antibody that blocks ligand binding to EGFR and HER3 (Schaefer et al.) had partial responses. To further explore the hypothesis that high-level HRG expression defines a sub-population of SCCHN that may be sensitive to agents targeting HER3, and to identify other potential target indications for the development of MEHD7954A, we evaluated the expression of HRG in large cohorts of multiple solid tumor indications. Methods: HER3 and HRG expression was analyzed by qRT-PCR in 648 formalin-fixed paraffin embedded primary tumor samples from patients with NSCLC, SCCHN, melanoma, CRC and triple-negative breast cancer. Results: SCCHN-derived tumor samples had the highest levels of HRG expression, exhibiting a bimodal distribution in SCCHN – a pattern that is clearly distinct when compared to other tumor types. These data suggest that high HRG levels and potentially HER3-dependent autocrine signaling occur more frequently in SCCHN than in other tumors. Further we investigated whether overexpression of HRG in SCCHN correlated with stage and disease outcome. Updated results from these extended studies will be presented. Conclusions: SCCHN tumors exhibit bimodal expression of HRG, suggesting that HRG expression levels may be useful in identifying a subset of patients most likely to benefit from inhibition of HER3 activity. Antitumor activity in such patients has been observed in a phase I study of MEHD7954A (abstract #95245).
A prognostic model for early recurrence prediction in hepatocellular carcinoma after liver resection.
Authors: Dan-Yun Ruan, Yang Li, Nan Jiang, Ze-Xiao Lin, XiangBo Wan, Xing Li, Xiang-Yuan Wu, Guihua Chen
Journal: Journal of Clinical Oncology (2013)

e15021 Background: Recurrence resulting in high morbidity of hepatocellular carcinoma (HCC) patients received radical liver resection, the majority of which occur within 1 to 3 years. The study aims to find risk factors and set up a prognostic model predicting early recurrence of HCC. Methods: From 2003 to 2010, 196 HCC patients underwent liver resection were retrospectively analyzed. Univariate and multivariate analyses were used to assess variables. A recurrence risk model was developed with independent prognostic factors. Area under the ROC curve (AUC) was carried out to evaluate its predictive value. Results: The median follow-up time was 33 months (1-103M), median RFS was 22 months. Total tumor volume (TTV), hepatitis B, Child-Pugh score, and portal vein tumor thrombus were independent factors of recurrence. Patients with TTV&gt;115cm 3 had worse RFS (28.9% vs 51.7%, p&lt;0.000) and OS (64.4% vs 80.1%, p=0.032) than those TTV≤115cm 3 . We established a risk model consisted of the 4 parameters, and classified patients into four stages. There were significant differences between each stage, especially for the 1st year. (1-yr RFS: 80.1% vs 47.8% vs 28.6% vs 0%, p=0.000, AUC 0.682). Compared to four currently used staging systems (BCLC, TNM, CLIP, and Okuda), the new model could well predict patient’s survival with the largest AUC in both RFS and OS (Table). Conclusions: TTV has been found a preferable description of tumor burden and a prognostic factor in HCC. This prognostic model predicts early tumor recurrence and survival of patients received radical liver resection and might contributes to the selection of patients who may benefit from surgery. [Table: see text]
Evaluation of psycho-social distress in patients treated in a community-based oncology group practice in Germany
Authors: U. Mergenthaler, J. Heymanns, H. Köppler, J. Thomalla, C. van Roye, R. Weide
Journal: Journal of Clinical Oncology (2009)

e20577 Background: Systematic evaluation of psycho-social distress in oncology outpatients is an important issue. Therefore we assessed feasibility and benefit of standardized routine screening using the Distress Thermometer (DT) and the Problem List (PL) in daily practice. Methods: All patients attending the practice between July and September 2008 were administered the DT and the PL. Patients were classified into the disease groups solid tumors, hematological neoplasms, benign hematological diseases and other non-malignant diseases. The individual treatment phase was evaluated additionally. Participants in a mammography screening programme were assessed as a control group. 500 randomly selected patients were sent a feedback-form to describe how they experienced the DT's influence on the doctor-patient-communication. Results: The 1,446 patients reported an average distress level of 4.7 with 37% indicating a distress level &gt; 5. Patients with other non-malignant diseases (81% autoimmune diseases or hereditary hemochromatosis) showed the highest average distress level of 5.2. Regarding the treatment phases, the most distressed patients were patients who just learned about their diagnosis of relapsed or metastatic disease (6.4), patients receiving Best Supportive Care (5.4) and patients receiving adjuvant anti-hormonal therapy (5.4). The most frequently indicated problems causing distress were exhaustion/fatigue (49%), pain (44%), impaired mobility (41%) and sleep disorders (39%) respectively. Breast cancer patients stated a distress level of 5.2. The average distress level in 474 mammography screening participants was 3.3. 37% of 190 patients who returned the feedback-form indicated that the DT and PL were useful tools to speak to their doctor about their distress more precisely. 38% felt better than usual after this conversation. Conclusions: The study shows that cancer patients do not necessarily show higher distress than patients with severe non-malignant diseases. The problems patients most frequently indicate as distressing are somatic disorders. DT and PL are applicable for routine screening in an outpatient setting. Physicians as well as patients stated that the use of the DT improved the quality of their communication. No significant financial relationships to disclose.
Randomized phase II study of recombinant human endostatin combined with definitive chemoradiotherapy in locally advanced esophageal squamous cell carcinoma.
Authors: Jiahua Lv, Tao Li, Xiaorong Deng, Fang Li, Yanqiong Song, Churong Li, Junchao Wang
Journal: Journal of Clinical Oncology (2015)

4035 Background: Recombinant human endostatin (endostar) has been documented to be an inhibitor of tumor angiogenesis. The aim of this randomized phase II study was to assess the efficacy and safety of endostar combined with chemoradiotherapy (CRT) in locally advanced esophageal squamous cell carcinoma (ESCC). Methods: Locally advanced ESCC with a performance status of 0-1 were randomly assigned to endostar group (endostar 7.5mg/m2 D1-D14 with CRT) or the control group (CRT only). Patients in both groups were treated with docetaxel (75 mg/m2 on D1)/CDDP (25 mg/m2 on D1-D3)-based intensity-modulated radiation therapy (IMRT, 60-66 Gy/30-33f/6-7wks). CT perfusion imaging and immunohistochemical staining of tumor microvessel density (MVD) were assessed before and after the treatment of endostar. The primary end point was overall survival (OS). The secondary end points were the effect of endostar on angiogenesis, progression-free survival (PFS) and object response rate (ORR). Results: Between Oct. 2012 and Sep. 2014, 63 patients were enrolled and divided into endostar group (n = 32) or the control group (n = 31). The endostar group resulted in a slight improvement in ORR (62.3% vs 55.1% in the control group), and a significant increase in the 1-year and 2-year overall survival rates (78.1% vs 67.7% and 56.2% vs 45.1%, respectively). The median PFS was extended to 16.5 months in the endostar group vs 9.3 months in the control group (P < 0.05). Endostar combined with CRT led to a marked decrease in tumor blood flow (BF) and blood volume (BV) with correction of MVD, compared to CRT alone (P < 0.05). There was no significant difference in toxicities in two arms. No new or unexpected endostar-related toxicities were observed. Conclusions: Recombinant human endostatin combined with CRT can reduce tumor angiogenesis. The short- and long-term effects of endostar combined with CRT were an improvement over that of CRT alone in this study. Clinical trial information: ChiCTR-TRC-13003908.