tbuckley/cabot-search huggingface dataset:
HER2 status as an independent prognostic marker in patients with advanced gastric cancer receiving adjuvant chemotherapy after curative gastrectomy.
Authors: Y. S. Park, M. Ryu, H. J. Park, H. J. Kim, B. Ryoo, J. H. Yook, B. S. Kim, S. J. Jang, Y. Kang
Journal: Journal of Clinical Oncology (2011)

4084 Background: It has been recently confirmed that trastuzumab, a monoclonal antibody against HER2, improves the overall survival in HER2 overexpressing gastric cancers. We investigated the prognostic significance of HER2 status in gastric cancers after curative gastrectomy and adjuvant chemotherapy. Methods: HER2 status was evaluated in 679 gastric cancer patients who recieved curative gastrectomy and adjuvant chemotherapy. All were enrolled in a phase III clinical trial from January 2002 to July 2006 in Asan Medical Center. Tissue microarrays were constructed using two independent cores form each case. Immunohistochemical (IHC) staining was scored by gastric cancer scoring system. Double silver-enhanced in situ hybridization (SISH) was done using HER2 probe and chromosome 17 centromere oligoprobe (CEP17). IHC score 2+ or 3+, and HER2/CEP17 ratio ≥2.0 were considered positive for IHC and SISH, respectively. IHC 3+ or IHC 2+ and SISH positive cases were defined as “HER2 status-positive”. Results: HER2 IHC-positivity (9.7%), SISH-positivity (12.2%) and HER2 status-positivity (8.3%) were all associated with differentiated or intestinal type histology and distal gastrectomy. IHC-positivity (P = 0.315), SISH-positivity (P = 0.382) and HER2 status-positivity (P = 0.277) showed negative correlation with the recurrence-free survival (RFS) but did not show statistical significance. However, in subgroup analyses according to the stage grouping (II vs. III+IV), HER2 status-positivity was a poor prognostic factor in advanced stage group (P = 0.001) but not in earlier stage (P = 0.827). The HER2 status-positivity remained as an independent prognostic factor after multivariate analysis (P = 0.023, HR = 1.709). Conclusions: HER2 status, taking both protein expression and gene amplification into consideration, was proved to be an independent poor prognostic marker for RFS in advanced stage gastric cancers after curative gastrectomy. Since it has been shown that HER2 status-positive patients benefited from trastuzumab therapy in unresectable gastric cancer patients, trastuzumab may play a role in locally advanced gastric cancer patients as adjuvant therapy.
Internet and social media use by patients in a comprehensive cancer center.
Authors: L. C. Smith, M. A. Kirch, P. M. Clark, K. J. Hammelef, M. B. Waldinger, L. C. An
Journal: Journal of Clinical Oncology (2011)

e19594 Background: Internet searches for health information are increasingly popular with American adults; 80% of Americans with Internet access search for health information. The use of social sites (Facebook or Twitter) doubled in those > age 50 in 2010. Understanding these quickly growing media could help improve information for cancer patients. The purpose of this study was to learn how cancer patients find and use information on cancer. Methods: We surveyed adult cancer patients (n = 1,282) at the University of Michigan Comprehensive Cancer Center in 2010 (response rate=75%). This pen and paper survey took 15 minutes to complete and assessed use of computers, Internet, social media, and usefulness of these information sources. Data analysis includes bivariate associations with Chi2 statistics. Results: Overall, 88% of respondents reported using the Internet with 93% of Internet users reporting broadband Internet access. Rates of Internet use were similar across diagnoses: breast cancer 91%, prostate cancer 86%, leukemia 88%. Young age and formal education were related to higher rates of Internet use. Overall, 47% of online patients reported using social media sites (44% Facebook, 5% MySpace, 4% Twitter). Most were relatively new users of social media (50% began in the past 2 years). Rates of social media use differed by cancer diagnoses: breast cancer 50%, leukemia 48%, prostate cancer 31%. Overall, 82% of patients reported that the Internet was useful or very useful in finding information about cancer. Only 30% of patients reported social media was a useful source of cancer information. Conclusions: Our study shows that a majority of patients have broadband access and use the Internet. A substantial proportion of patients also reported use of online social media. Rates of Internet are similar for patients across a range of cancer diagnoses, while social media use varied. However, the usefulness of cancer information from these sources is deemed limited by respondents. There may be great opportunity to increase the usefulness of online cancer information, especially via online social media channels. Future work could assess Internet and social media use by patients in a wider range of settings or in population-based samples of cancer patients.
Prognostic factors after R2 surgery in patients with advanced gastric cancer.
Authors: Masanori Tokunaga, Hironobu Goto, Rie Makuuchi, Yutaka Tanizawa, Etsuro Bando, Taiichi Kawamura, Masanori Terashima
Journal: Journal of Clinical Oncology (2013)

140 Background: In patients with advanced gastric cancer, chemotherapy is a standard treatment if they have non-curable factors. However, gastrectomy is sometimes performed even in patients having non-curable factors, particularly when they have tumor associated symptoms. The aim of this study is to investigate clinicopathological characteristics of patients who underwent R2 surgery, and to identify prognostic factors. Methods: This study included 157 patients who underwent gastrectomy with macroscopic residual disease (R2 surgery) between September 2002 and June 2011 at the Shizuoka Cancer Center. Clinicopathological characteristics and surgical outcomes were investigated. In addition, we conducted Cox-proportional Hazards model which included age, sex, number of non-curable factors, chemotherapy, macroscopic type, histology, and postoperative intraabdominal infectious complications as covariates, to identify independent prognostic factors after R2 surgery. Results: There were 103 male and 54 female patients with median age of 69 years. The reasons why R2 surgery was performed were low oral intake due to stenosis in 120 patients and bleeding in 54 patients. Total gastrectmy was the most frequently performed procedure (93 patients) followed by distal gastrectomy (61 patients) Median operation time and intraoperative blood loss were 193 minutes and 337 mg, respectively, and intraabdominal infectious complications (Clavien-Dindo classification grade II or more severe) were observed in 24 patients (15.3%). Chemotherapy was given after surgery in 112 patients (71.3%) with median survival time of all patients being 8.7 months. Multivariate analysis identified postoperative chemotherapy (Hazard ratio, 0.34; 95% confidential interval, 0.24 – 0.65) and postoperative intraabdominal infectious complications (Hazard ratio, 1.74; 95% confidential interval, 1.06 – 2.88) as independent prognostic factors. Conclusions: The incidence of postoperative infectious complications after R2 surgery was thought to be higher than that after curative gastrectomy reported before. Safe procedure and administration of postoperative chemotherapy would be necessary to offer improved overall survival after R2 surgery.
Racial/ethnic disparities in HER2-positive breast cancer in the era of adjuvant trastuzmab.
Authors: Vincent Caggiano, Carol Parise
Journal: Journal of Clinical Oncology (2015)

139 Background: Racial/ethnic disparities in breast cancer survival have been well-documented. Trastuzumab was FDA approved for adjuvant treatment of HER2-positive breast cancer in November, 2006 and has improved survival in these patients. The purpose of this study is to determine if racial disparities have changed in patients who were diagnosed with HER2 positive breast cancer in 2007-2012 when compared with patients who were diagnosed in 2000-2006. Methods: Using the California Cancer Registry, we identified 32,597 cases of first primary female invasive HER2-postive breast cancer. Cases were divided into two cohorts: Early - diagnosed in 2000-2006; Late - diagnosed in 2007-2012. Kaplan-Meier 6-year survival and Cox regression analysis was conducted to assess risk of mortality of African Americans, Hispanics, Asian/Pacific Islanders, and American Indians when compared with whites. Analyses were conducted separately for each cohort and adjusted for stage at diagnosis, grade, age, and socioeconomic status. Hazard ratios and 95% confidence intervals were reported. Use of trastuzumab was not documented. Results: When combining all HER2-positive subtypes (ER+/PR+/HER2+, ER-/PR+/HER2+, ER+/PR-/HER2+, ER-/PR-/HER2+), blacks had an increased risk of mortality (HR = 1.32; 95% CI: 1.16-1.49), in the early cohort but there were no differences for any other race. There were no differences in mortality by race/ethnicity in the late cohort. Separation of the HER2-positive subtypes showed that African Americans with the ER+/PR+/HER2+ subtype had higher mortality than whites (HR = 1.43; 95% CI: 1.17-1.75) in the early cohort but there was no difference in the late cohort. There were no racial disparities within either of the cohorts for the ER-/PR-/HER2+ subtype. Conclusions: Although we were unable to document use of anti-HER2 treatment, the era of adjuvant trastuzumab appears to have attenuated the black/white disparity in HER2 positive breast cancer.
Predictors of trajectories of cognitive change in women with breast cancer.
Authors: Catherine M Bender, John Merriman, Amanda Gentry, Gretchen M. Ahrendt, Adam Brufsky, Susan M. Sereika
Journal: Journal of Clinical Oncology (2016)

149 Background: Subgroups of women with breast cancer may be vulnerable to cognitive changes with systemic therapy. Given our previous findings of changes in concentration and working memory (WM), we sought to identify subgroups of women with distinct trajectories of concentration and WM and determine predictors of subgroup membership. Methods: Cognitive function was assessed before systemic therapy and semi-annually to 18 months post-therapy initiation in 181 postmenopausal women with breast cancer who received the AI, anastrozole, or chemotherapy+anastrozole and at matched time points for 110 healthy controls. Group-based trajectory modeling identified subgroups of women with distinct trajectories of concentration and WM (as measured by composites of mean z-scores for neuropsychological tests). Multinomial logistic regression identified predictors of subgroup membership. Results: A 3-group model was found for concentration: low and constant (25%; b0 = -0.84), normal but declining (65%; b0 = 0.05, b1 = -0.04), and high and constant (10%; b0 = 1.29). At baseline, the low subgroup was older (p = .009) and had lower psychomotor speed (p = .035) than the normal subgroup. Controlling for baseline concentration z-scores, membership in the low concentration subgroup was associated with greater age (p &lt; .001), more fatigue (p &lt; .001), and poorer self-reported cognitive function (p = .001). For WM, a 2-group model was identified: low and increasing (35%; b0 = -0.67, b1 = 0.11) and high and increasing (65%; b0 = 0.32, b1 = 0.07). At baseline, the low WM subgroup was older (p = .008), had less education (p &lt; .001), and scored lower on the NART verbal IQ test (p &lt; .001). Controlling for baseline WM z-scores, membership in the low WM subgroup was associated with poorer executive function (p &lt; .001), receipt of anastrozole alone (p = .011), and worse pain (p = .002) and anxiety (p = .008). Conclusions: Subgroups of women are more vulnerable to poorer concentration and WM during adjuvant therapy for breast cancer. Advancing age, less education, and co-occurring symptoms are associated with membership in these vulnerable subgroups.
Radical prostatectomy as a component of multimodal therapy for highly selected M1 prostate cancer patients.
Authors: Matthew O'Shaughnessy, James Andrew Eastham, Bernard H. Bochner, Vincent Paul Laudone, Brett Stewart Carver, Daniel Sjoberg, Peter T. Scardino, Howard I. Scher, Karim A. Touijer
Journal: Journal of Clinical Oncology (2015)

251 Background: Men who present with limited metastasis at the time of prostate cancer (PCa) diagnosis are typically managed with systemic therapy alone and the primary site of disease is not addressed. Systemic therapy with recently approved agents has been shown to improve survival in men with metastatic PCa; however the role of local therapy remains untested. Here, we examine the role of definitive surgical treatment of the primary tumor in a multimodal approach to highly selected patients with oligometastatic disease to maximize local and systemic cancer control. Methods: 20 patients with limited metastatic burden underwent RP as a component of multimodal therapy. Baseline characteristics, details of management, surgical outcomes, and disease progression defined as initiation of chemotherapy, new metastasis, or reinitiation of ADT were characterized. Results: Median age at RP was 61 years. Metastatic burden was assessed with whole body imaging; 17 of 20 patients had bone metastases (mets) (median 1, IQR 1,3) and 7 of 20 patients had retroperitoneal node mets. No patients had visceral mets. All patients had RP and pelvic lymph node dissection; 4 patients also had retroperitoneal lymph node dissection. There was one grade III surgical complication. 75% of patients reported continence within 12 months of RP. Patients received RT to bone (n=10), bone and pelvis (n=4), or no RT (n=6). Median neoadjuvant ADT was 4 months (IQR 3, 5) for all patients and neoadjuvant + adjuvant ADT was 9 months (IQR 6, 10) in 11 patients who discontinued ADT. At median follow-up of 19 months (IQR 10, 33) since RP, 12-month PFS was 65% (95%CI 35, 84). Among the 11 patients who discontinued ADT, 5 were non-castrate and had no evidence of disease progression. 4 patients had continuous ADT due to disease progression. There were no local recurrences after surgery. Conclusions: Multimodal therapy that includes RP is feasible and well-tolerated with acceptable low rate of surgical complications and good return of urinary continence. ADT was discontinued in a limited number of patients without signs of disease progression at short-term follow-up. Further evaluation of this therapeutic strategy should be considered in a prospective clinical trial.
Weekly nab-paclitaxel followed by FEC in patients with operable breast cancer: Phase II study.
Authors: Hirohito Seki, Fumiki Asamuna, Shyoujiro Morinaga, Keiichi Suzuki, Munehisa Kaneda, Noriki Kamiya, Yoshiyuki Ishii, Masayoshi Osaku, Tadashi Ikeda
Journal: Journal of Clinical Oncology (2015)

138 Background: Nanoparticle albumin-bound paclitaxel (nab-PTX) has a high transitivity into tumor tissue compared to solvent-based paclitaxel (sb-PTX). In a phase III study in patients with metastatic breast cancer, nab–PTX demonstrated nearly double the response rate and significantly longer time to tumor progression than paclitaxel. However, the current problems are that nab-PTX is a higher rate of discontinuation and sensory neuropathy than sb-PTX. We sought to evaluate the efficacy and safety of nab-PTX followed by FEC. Methods: In this study, patients were received 4 cycles of nab-PTX (80 mg/m 2 ) q1w (days 1, 8, and 15 of each 4-week cycle) followed by 4 cycles of FEC q3w. The primary endpoint was pCR rate (ypT0/is ypN0). The secondary endpoints included clinical response rate, disease-free survival, breast-conserving surgery rate, and safety. Results: Forty patients were enrolled; the median age was 53 (range 33-81), postmenopausal women were 62.5%. ER positivity, PgR positivity and HER2 positivity were 62.5%, 52.5% and 37.5%, respectively. Clinical stage for I, II and III were 30%, 62.5% and 7.5%, respectively. The pCR rate (ypT0/is ypN0) was 40% (16/40). In the subtype subset, pCR rates were Luminal A 20% (1/5), Luminal B (HER2 negative) 15.4% (2/13), Luminal B (HER2 positive) 60% (6/10), HER2 enrich 80% (4/5) and TNBC 42.9% (3/7). The breast-conserving surgery rate was 77.5% (31/40). The clinical response rates were cCR 20.0% (8/40), cPR 52.5% (21/40), cSD 25% (10/40) and cPD 2.5% (1/40) after 4 cycles of nab-PTX, cCR 32.5% (13/40), cPR 42.5% (17/40), cSD 20% (8/40) and cPD 5% (2/40) after nab-PTX followed by FEC. Ninety-eight percent patients completed 4 cycles of planned protocol dose of nab-PTX and 62.5% completed FEC. The Grade3/4 hematologic toxicity of nab-PTX was only neutropenia 2.5%. Grade1/2 non-hematologic toxicity were neuropathy 12.5%, arthralgia 7.5% and myalgia 7.5%. Grade3/4 non-hematologic toxicity was no reported. Conclusions: This is the first study to evaluate weekly nab-PTX (80 mg/m 2 ) followed by FEC for operable breast cancer. Our results demonstrated that weekly nab-PTX (80 mg/m 2 ) followed by FEC was well-tolerated and resulted in increased pCR rate than reported data of nab-PTX. Clinical trial information: UMIN000011048.
Relationship of sipuleucel-T with time to first use of opioid analgesics (TFOA) in patients (pts) with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC) on the IMPACT trial.
Authors: Eric Jay Small, Celestia S. Higano, Philip W. Kantoff, James Boyd Whitmore, Mark Walter Frohlich, Daniel Peter Petrylak
Journal: Journal of Clinical Oncology (2013)

74 Background: Sipuleucel-T (sip-T) is an autologous cellular immunotherapy which was shown to prolong survival in pts with mCRPC in the pivotal IMPACT trial (NCT00065442) (Kantoff PW et al. N Engl J Med 2010;363:411-22). TFOA was a prespecified secondary end point but was subsequently removed as an end point following a protocol amendment to expand enrollment to include minimally symptomatic pts in addition to asymptomatic pts. TFOA data were nevertheless collected in the 512 pts enrolled in the trial. Methods: At baseline, pts were required to have an average pain score &lt;4 on a 10-point visual analog scale and no ongoing opioid analgesic use (OAU). Concomitant medications were collected until confirmed objective disease progression. OAU was identified by medical review of preferred drug names in the coded concomitant medication information on case report forms (CRFs). OAU unrelated to cancer pain (e.g. meperidine used for infusion reactions) was excluded by medical review of CRFs. Pts not reporting OAU were censored at the time of protocol amendment. TFOA was analyzed using a Cox regression model with adjustment for baseline PSA and LDH. Results: 341 sip-T- and 171 placebo-treated patients were evaluated. Median TFOA was 11.9 months (mo) with sip-T vs 8.3 mo for placebo (hazard ratio=0.727; 95% confidence interval 0.536, 0.987; p=0.041). Censoring rate was high (sip-T, 66.9%; placebo, 61.4%). Median follow-up for OAU was 5.2 mo (sip-T, 5.3 mo; placebo, 5.0 mo). Kaplan-Meier estimates of being opioid free at 12 mo were 48.7% for sip-T vs 39.7% for placebo; curve separation began at 6 mo. Significant independent baseline predictors of shorter TFOA were: higher PSA, alkaline phosphatase; younger age; higher number of bone metastases; Gleason score ≥8; ECOG performance status 1; higher weight; and prior primary radiotherapy. Conclusions: Relative to placebo, sip-T delays the TFOA in patients with asymptomatic or minimally symptomatic mCRPC. Clinical trial information: NCT00065442.
The minimal effective relative dose intensity (RDI) for modified FOLFIRINOX in advanced pancreatic cancer: Suggestion for modified Hryniuk’s calculation method.
Authors: Jong-chan Lee, Kyu-hyun Paik, Hyoung Woo Kim, Jingu Kang, Young Soo Park, Jaihwan Kim, Jin-Hyeok Hwang
Journal: Journal of Clinical Oncology (2016)

402 Background: Since FOLFIRINOX (5-fluorouracil, oxaliplatin, leucovorin and irinotecan) improved efficacy but also increased toxicity in pancreatic ductal adenocarcinoma (PDA) patients, several reports have been published about modified FOLFIRINOX as a concept of dose reduction. However, the lower limit of dose reduction is still unclear. The aim of this study is to find the minimal relative dose intensity (RDI, %) of FOLFIRINOX that can be expected to yield tumor response in advanced pancreatic ductal adenocarcinoma. Methods: A total of 95 PDA patients treated with FOLFIRINOX as a first line therapy were retrospectively reviewed. Based on Hryniuk’s arithmetic formula, we defined an extended Hryniuk’s calculation and launched a calculator site ( http://www.rdicalc.com ). Using receiver operator characteristic (ROC) curve, we investigated minimal RDI with a view to obtaining tumor response rate (RR) and disease control rate (DCR). The toxicity profile was also described. Results: Among the 95 patients, 85 patients completed the initial treatment until the first radiological evaluation with median 3 cycles and 56 days. Thirty one patients had locally advanced PDAC and 54 had metastatic disease. As the minimal effective thresholds, the ROC curve showed 71.5% RDI for RR (78.1% sensitivity, 83.0% specificity) and 54.5% RDI for DCR (91.3% sensitivity, 56.3% specificity). When divided by 5% units, the minimal RDI for RR and DCR was 70% and 55%, respectively. Among the 95 patients, including the dropout group, grade III/IV neutropenia, febrile neutropenia and vomiting was 45%, 13% and 31%, respectively. Early period toxicities and RDI did not show dose-response relationships. Conclusions: Although reduced dose FOLFIRINOX could be effective in advanced PDAC, our data suggest that more than 70% RDI for RR and 55% for DCR should be preserved. Toxicity rates were not influenced by RDI level in the early therapeutic period.
Analysis of prognosis in non-small cell lung cancer patients with platinum-based chemotherapy and bone marrow suppression.
Authors: B. Han
Journal: Journal of Clinical Oncology (2011)

e17532 Background: Platinum-based chemotherapy is the first-line treatment for the advanced non-small cell lung cancer (NSCLC). Bone marrow suppression is one of the most important systemic toxicity of it. This study is to analyze clinical conditions and prognosis of the metastatic NSCLC patients treated with platinum chemotherapy and with bone marrow suppression after chemotherapy. Methods: Medical records of 309 metastatic NSCLC patients receiving first-line platinum chemotherapy were collected and analyzed retrospectively. According to the National Cancer Institute common toxicity criteria, the groups were divided by the degree of leucopenia, thrombocytopenia and hemoglobin reduction, respectively. Total effective rate (ORR), disease control rate (DCR), time to disease progression in patients (TTP) and overall survival (OS) were compared. Results: ORRs, DCRs, TTPs, and OSs of each group were listed in the Table. Comparisons in the groups divided by the degree of leucopenia showed that ORRs between the 3 groups were significantly different. There was no significant difference of TTPs or OSs compared in the 2 inhibition groups. In the comparisons between the 3 groups divided by the degree of thrombocytopenia, significant difference was found in ORRs. Comparing with the no inhibition group, significant difference was in TTPs of the 2 suppression groups and OS of the mild inhibition group. The comparisons in the 3 groups divided by the degree of hemoglobin reduction found significant difference in ORRs, not in TTPs or OSs. Conclusions: This study showed that chemotherapy associated leukopenia and thrombocytopenia was the emergence of indicators of good prognosis, but chemotherapy-related anemia was inaccurate predictor of the prognosis. Groups divided by the degree of Groups Without inhibiting Mild inhibition Moderate and severe suppression Leucopenia ORR (%) 3.2 14.5 25.5 DCR (%) 27.4 72.4 82.4 TPP (months) 2.0 5.88 7.44 OS (months) 7.64 14.69 13.72 Thrombocytopenia ORR (%) 9.2 18.4 3.3 DCR (%) 27.4 79.8 81.0 TPP (months) 3.85 6.71 7.36 OS (months) 12.30 14.89 12.77 Hemoglobin reduction ORR (%) 8.8 19.3 24.1 DCR (%) 54.9 73.5 75.9 TPP (months) 3.73 5.95 6.87 OS (months) 12.65 13.15 13.02