tbuckley/cabot-search huggingface dataset:
Surgical pathology and the patient: A systematic review evaluating the primary audience of pathology reports.
Authors: Matthew Mossanen, Jonathan L. Wright, Lawrence D. True, Funda Vakar-Lopez, Danielle Lavallee, John L. Gore
Journal: Journal of Clinical Oncology (2014)

261 Background: For patients with a diagnosis of cancer, the pathology reports represent a sentinel document that dictates prognosis and management. However, a substantial subset of patients may lack the ability to comprehend this complex document while making medical decisions. As a result, many cancer patients may stand to benefit from more patient-centered pathology reports. We sought to review the available literature in order to identify the primary audience of surgical pathology reports for the most common malignancies in men and women in the U.S. Methods: A systematic review was conducted using PubMed,MEDLINEdatabases, Cochrane Reviews,and Google Scholar. Data from the American Cancer Society were used to determine the most common cancers projected for 2013 for men and women in the U.S. (prostate and breast cancer, respectively, followed by lung and colorectal cancers). An expert panel developed a list of search criteria and an iterative search was performed and articles were screened for relevance. We summarize the results of the literature search with descriptive statistics. Results: No articles addressed the patient as the target audience of oncologic pathology reports. No articles evaluated the readability of pathology reports or literacy levels required to interpret pathology reports. We did not identify any articles that described standardized approaches for discussing the pathology of the most common cancers in men and women with patients or their caregivers. Twelve articles were devoted to renovation of pathology reports to promote the exchange of information between physicians, most of which (58%) addressed breast cancer pathology. Conclusions: Patient-centered cancer communication is a common theme in the care of oncology patients and represents an important metric in determining patient satisfaction. Yet, oncologic pathology reports do not include patients or their caregivers as target audiences. Limited resources are available to help patients comprehend their pathology reports. Efforts to improve patient centered communication, such as through the use of patient-centered pathology reports, may address this overlooked aspect of cancer care.
A randomized multi-center phase II trial of capecitabine (X) versus S-1 (S) as first-line treatment in elderly patients with metastatic or recurrent unresectable gastric cancer
Authors: Y. Kang, J. Lee, Y. Min, K. Lee, D. Zang, B. Ryoo, J. Kim, S. Park, W. Kang, D. Shin
Journal: Journal of Clinical Oncology (2007)

4546 Background: Although the combination chemotherapy is the standard of care for young patients (pts) with advanced gastric cancer (AGC), single agent chemotherapy may be a good alternative for elderly pts. Recent introduction of two new generation oral fluoropyrimidines, capecitabine and S-1, prompted us to investigate the activity and safety of these agents in elderly pts with AGC in a randomized multi-center phase II design. ( NCT00278863 ) Methods: Elderly chemo-naïve pts (= 65 years) with measurable metastatic or recurrent gastric cancer were randomly assigned to receive capecitabine (1,250 mg/m 2 bid, D1–14 every 3 weeks, arm X) or S-1 (40∼60 mg bid according to BSA, D1–28 every 6 weeks, arm S). The primary endpoint was the response rate (RR). Results: From Oct 2004 to Apr 2006, 96 pts were enrolled. Excluding 5 pts who did not fit inclusion criteria, 91 pts were randomized to arm X (N=46) or arm S (N=45). Median age was 70.5 years for arm S and 71.0 years for arm X. Other clinical and tumor characteristics were well balanced across the two treatment arms. Among 44 assessable pts in arm X, 13 attained partial response (PR, 29.5%), 17 stable disease (SD, 38.6%) and 10 progressive disease (PD); 4 pts were not evaluable (NE). The corresponding disease responses in the 45 assessable pts in arm S were: 1 complete response (2.2%), 12 PR (26.7%), 18 SD (40.0%), 10 PD, and 4 NE. The incidence of grade 3–4 granulocytopenia was 6.8% in arm X and 4.8% in arm S. One episode of febrile neutropenia was observed in arm X. Grade 3–4 non-hematologic toxicities were as follows (arm X vs. S): asthenia (0% vs. 7.2%), anorexia (6.8% vs. 9.5%), diarrhea (2.3% vs. 0%), and HFS (6.8% vs. 0%). With a median follow up of 13.5 months (mo) for survivors (range, 8.1∼21.9), median time to progression and time to treatment failure were 4.8 mo (95% CI, 3.0–6.5) and 4.4 mo (3.6–5.3) for arm X and 4.2 mo (1.5–6.9) and 3.0 mo (1.5–4.5) for arm S. Median overall survival was 10.0 mo (8.0–12.0) for arm X and 7.9 mo (4.1–11.7) for arm S. Conclusions: Both treatments were active and tolerable as a 1 st line treatment for elderly pts with AGC. No significant financial relationships to disclose.
Exploration of biomarkers for lymph node metastasis in patients with endometrial cancer using exon-expression microarray.
Authors: S. Sudo, Y. Konno, T. Odagiri, T. Kato, M. Hosaka, M. Takeda, H. Watari, M. Kaneuchi, N. Sakuragi
Journal: Journal of Clinical Oncology (2011)

5100 Background: To predict possibility of lymph node metastasis using primary cancer tissue preoperatively, we explored putative biomarker genes of node metastasis in patients with endometrial cancer. Methods: mRNAs were extracted from primary cancer tissues of patients underwent hysterectomy, bilateral salpingo-oophorectomy with pelvic and para-aortic lymphadenectomy in our institute from August 2001 to December 2010. Affymetrix Exon Microarray sorted out transcripts showing significantly different expression between node-negative and node-positive groups. To validate microarray results, realtime PCR with Taqman(R) Gene Expression Assays were employed. Twenty-seven and 61 mRNA samples with endometrioid adenocarcinoma were used for microarray and realtime PCR, respectively. For statistical analyses of microarray results, ArrayAssist 5.0 was used. Results: Expression levels of 6 transcripts, ANKRD36 (ankyrin repeat domain containing 36), VPS13A, ZNF577, CROP (cisplatin resistance-associated overexpressed protein), MALAT-1 (metastasis-associated lung adenocarcinoma transcript 1) and TIMP3 (tissue inhibitor of metalloproteinase 3) showed significant differences between node-negative and node-positive groups in microarray analyses. For the validation, realtime PCR narrowed down 6 candidates to 4 upregulated transcripts in node-positive samples; ANKRD36, VPS13A, CROP and MALAT-1. Using custom-made peptide antibody against ANKRD36 protein and commercially available anti-CROP antibody, immunostaining analyses were performed. Interestingly, immunostaining intensity for ANKRD36 and CROP in paraffin-embedded carcinoma tissues corresponded to mRNA expression levels of realtime PCR analyses. Metastatic lymph node also showed positive for both of ANKRD36 and CROP. Conclusions: We have identified 4 upregulated transcripts in primary cancer focus of node-positive endometrial cancer. They might be the putative node-positive biomarkers in endometrial cancer.
Acquisition of HER2/neu over-expression on circulating tumor cells (CTCs) in patients (pts) with advanced breast cancer (ABC) during chemotherapy
Authors: E. Munzone, F. Nolé, L. Zorzino, M. Medici, I. Minchella, M. C. Cassatella, C. Casadio, M. Picozzi, L. Adamoli, A. Goldhirsch, M. Sandri
Journal: Journal of Clinical Oncology (2008)

11017 Background: CTCs can be detected and isolated from the peripheral blood of women with ABC. In addition to enumeration, an exciting area of research involves the phenotyping and expression profiling of CTCs. In this regard, assessing the presence of target antigens on CTCs could be considered as a real-time biopsy allowing the possibility to evaluate the change in tumour phenotype during the clinical course of the disease. HER2/neu status of tumor cells detected in metastatic sites may differ from the original primary tumor in about 5–20% of cases. Furthermore, there is evidence that nearly one third of pts whose primary tumors were HER2/neu negative might have amplified HER2/neu on CTCs. Methods: We collected 7.5 ml blood samples from each of 40 pts with ABC. CTCs were isolated with the CellSearch System® (Immunicon Co.) by means of immunomagnetic separation, using ferrofluid nanoparticles binding anti-epithelial cell adhesion molecules (EpCAM), and fluorescently stained with Epithelial Cell Kit®. CTCs were defined as nucleated (DAPI positive), epithelial (CK 8, 18, 19 positive) and negative for CD45. Concomitantly, we used Tumor Phenotyping Reagent® to investigate HER2/neu expression. Moreover, CTCs were isolated using the Profile Kit®: slides were set up and investigated by immuno-cyto-chemistry and fluorescence in-situ hybridization (FISH). Our goal was to evaluate the concordance of HER-2/neu expression between the pathological primary tumor analysis and CTCs and the acquisition of HER-2/neu overexpression on CTCs during the course of chemotherapy. Results: CTCs were detected in 32 pts (80%), median CTCs number was 3 (range 1–710). Ten pts had HER2/neu overexpression on primary tumor. One pt (10%), while receiving a trastuzumab based treatment, resulted HER2/neu negative on all 25 CTCs detected. The concordance between the primary tumor and CTCs was 90%. Twenty-two pts did not overexpressed HER2/neu on primary tumor and 6 of them (27%) acquired HER2/neu overexpression on CTCs during chemotherapy. Conclusions: HER2/neu overexpression can be acquired during the course of chemotherapy in pts with ABC. Our future intent is to evaluate the efficacy of a trastuzumab based therapy in this sub-group of pts. No significant financial relationships to disclose.
A phase I study of G3139 in combination with RICE chemotherapy in relapsed non-Hodgkin’s lymphoma (NHL)
Authors: S. M. Smith, K. Van Besien, K. Conner, T. Gajewski, T. Kuna, T. Karrison, J. L. Wade Iii, J. Zwiebel, E. E. Vokes
Journal: Journal of Clinical Oncology (2006)

17529 Background: Aggressive lymphomas are chemosensitive, but frequently relapse. Bcl-2 protein overexpression promotes tumor cell survival via anti-apoptosis, and is clinically correlated with shortened remission duration and decreased survival. The antisense oligonucleotide oblimersen sodium (G3139) downregulates bcl-2, has activity in NHL, and may be synergistic with chemotherapy. Methods: Pts had histologically confirmed aggressive NHL that relapsed after one prior anthracycline-based regimen. G3139 was given as a continuous infusion on Days 1–8 (168 hours) every 14 days, with stem cell collection following cycle 3. Standard RICE chemotherapy was given on Days 4–6, allowing 72 hrs pre- and 48 hrs post-chemo G3139. Dose-limiting toxicity (DLT) was defined as grade 3 or greater non-hematologic toxicity, grade 4 thrombocytopenia, duration of neutropenia &lt;500/mL greater than 7 days despite growth factors, grade 3 hemolytic anemia, or prolonged severe anemia. Pharmacodynamic endpoints included measurement of bcl-2 protein in peripheral blood (FACS analysis) and tumor (IHC), and bcl-2 RT-PCR in blood and tumor. Results: 8 pts were enrolled. At dose level 1 (G3139 3 mg/kg/day), both enrolled pts had grade 4 thrombocytopenia. The next 6 patients were treated with G3139 2.5 mg/kg/day (Dose Level -1) without any DLT’s. There were no grade 3 or 4 non-hematologic toxicities. 7 evaluable pts had successful stem cell collections: median CD34+ 4.2 × 10 6 /kg (range, 1.3–8.72 × 10 6 /kg). Responses: 4 CR/CRu, 2 PR, 1 SD, 1 too early. There was no detectable decrease in bcl-2 protein in the blood using flow cytometry or RT-PCR. Conclusion: The maximum tolerated dose of G3139 given over 8 days in combination with RICE chemotherapy is 2.5 mg/kg/day. It is unlikely that this dose sufficiently suppresses bcl-2 levels. The protocol will thus be amended to shorten the G3139 infusion to 5 days with renewed efforts to escalate the dose. No significant financial relationships to disclose.
Who should be considered for FOLFOX adjuvant chemotherapy? An analysis of Dukes B colorectal cancer in a Royal Marsden Hospital randomized trial
Authors: Y. J. Chua, A. R. Norman, A. Wotherspoon, D. Cunningham
Journal: Journal of Clinical Oncology (2005)

3559 Background: Based on the positive results of adjuvant fluoropyrimidine chemotherapy in Dukes B colorectal cancer in the QUASAR trial it is expected that more patients with this stage of disease will be offered chemotherapy. Furthermore the MOSAIC study has indicated a role for combination chemotherapy with FOLFOX in these patients. Thus we have conducted an analysis of the disease-free and overall survivals (DFS and OS) of the Dukes B patients from our multicentre randomized trial which compared two 5-FU based regimens (Mayo regimen versus protracted venous infusion) to determine the influence of other adverse clinical and histological prognostic factors on outcome. Methods: Patients were considered high risk if ≥1 of the following was present: poorly differentiated or mucinous tumours; T4 stage; extramural venous invasion; presentation with either perforation or obstruction. Results: Between 1993 and 2003, a total of 801 patients received treatment within the study. Of these, there were 277 Dukes B patients from RMH who were high (n=94) or low (n=183) risk. The proportion of patients from both treatment arms in both groups was well matched. The median follow-up at the time of analysis was 6.2 years. There have been 53 relapses and 58 deaths in the patient cohort to date.The 3-year DFS for the high and low risk groups was 70.9% [95% CI: 60.5–79.0%] and 87.9% [95% CI: 82.2–91.9%] respectively (HR=1.85 [95% CI: 1.13–3.04; p=0.0078]).The 5-year OS for the high and low risk groups was 77.6% [95% CI: 67.5–85.0%] and 86.7% [95% CI: 80.6–90.9%] respectively (HR=1.69 [95% CI: 0.97–2.96; p=0.0474]). In comparison, the 5-year OS for the entire group of Dukes C patients entered in the study was 67.3% [95%CI: 62.4–71.7%] respectively. Conclusions: Patients with Dukes B colorectal cancer who had at least one adverse prognostic feature, who received adjuvant chemotherapy with 5-FU alone, had a significantly worse OS (5-year OS 77.6% versus 86.7%) and DFS compared to those who did not have any such factors. This reinforces the case for adjuvant chemotherapy with FOLFOX in this group of patients. No significant financial relationships to disclose.
Can toremifene prevent bone loss in the orchiectomized rat?
Authors: S. Raghow, J. Okolicany, K. Veverka, M. S. Steiner
Journal: Journal of Clinical Oncology (2004)

8108 Background: Androgen-deprivation therapy leads to osteoporosis and bone fractures in men with prostate cancer. Selective estrogen receptor modulators (SERMs) which reduce bone resorption in females may also prevent osteoporosis and fractures in males. We tested the efficacy of toremifene (Tor), a SERM, to prevent bone loss in the castrated male rat. Methods: In a 6-wk study, fifty 8 mo-old male rats were divided into 5 groups (n=10): Sham, Orchiectomy (Orx), Orx+Tor (5mg/kg/d), Orx+Tor (10 mg/kg/d) and Orx+Estradiol (E, 0.2mg/kg/ml control). Treatment was initiated at castration via s.c. pump. Serum bone biomarkers osteocalcin (OC) and C-terminal telopeptides (CTX) were measured at 0, 1.5, 4 and 6 wks by ELISA. Prostate was weighed at necropsy. Tibia was analyzed by histomorphometry. Femur bone mineral density (BMD) and mechanical strength were measured by DEXA and Compression test, respectively. Results: Orx decreased prostate weight by 77%, significantly increased OC and CTX levels, decreased trabecular bone volume, and increased bone turnover significantly (p<0.05, orx vs. sham and treated groups). Orx increased osteoclast number, mineralization surface and bone formation rate (BFR/BS, BFR/BV, BFR/TV). E, 5 mg-Tor and 10 mg-Tor significantly reversed the Orx-related increase in OC and CTX levels, the effect of Tor being dose- and time-dependent. The Orx-induced increase in bone turnover parameters was also reversed by both E and Tor although the change was statistically nonsignificant. Orx resulted in loss of BMD in proximal- and distal-femur and while 5 mg-Tor was ineffective 10 mg-Tor and E prevented this loss. Both E and 10 mg-Tor had equal effect on the proximal-femur BMD and the effect of E on distal-femur was significant (p ≤ 0.01, E vs. Orx group). No statistically significant difference was observed in femur strength between Tor or E versus the Orx group. E or Tor had no effect on prostate weight in the Orx rat. Conclusions: Toremifene reduced bone turnover, prevented bone density loss and protected bone microarchitecture in the Orx rat. These studies suggest that toremifene may prevent bone loss and protect bone quality in prostate cancer patients treated by androgen-deprivation therapy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GTx, Inc. GTx, Inc.
Vascular endothelial growth factor (VEGF) is associated with reduced NK-like T cells in ascites and suppresses lymphocytes in cell cultures: Prognostic implications of VEGF in ascites from ovarian cancer
Authors: M. Tsiatas, R. Gyftaki, C. Liakos, A. Ziogas, M. A. Dimopoulos, A. Bamias
Journal: Journal of Clinical Oncology (2008)

16505 Background: We have shown that CD4+CD25+ Tregs and CD3+CD56+ NK-like T cells are significantly increased in the ascites from ovarian cancer compared with ascites from cirrhosis or blood from the same patients (Gynecol Oncol 2007; 106: 75–81, 2007). Both populations are involved in the immune response against the tumor. Since VEGF may be involved in immune regulation, we studied its association with these populations and prognosis. We also studied this relationship by ex vivo expansion of these cells in culture. Methods: 64 patients with ovarian cancer were included. VEGF, TNFa, IFNγ, IL-10 and IL-12 in ascites and serum were measured by ELISA, while cell populations and expression of VEGF receptors were studied with flow cytometry. For tissue culture experiments, 6 × 106 cells were plated on Petri dishes and were pulsed with IL-2, anti-CD3 and IFN-γ in order to expand CD3+ and CD56+ cells. Blood from healthy individuals was also analysed. VEGF at 0, 20, 100 and 500 pg/ml was also added to the cultures. Each concentration was tested in triplicate. Results: VEGF ascites levels were inversely correlated with CD3+CD56+ cells (rho= -0.316, p=0.012). Among patients receiving first-line chemotherapy (n=42), VEGF levels ≤ 1,900 pg/ml were associated with platinum sensitivity (p=0.030), improved progression-free survival (17 vs. 9 months, p=0.028) and overall survival (not reached vs. 20 months, p=0.045). Cell culture experiments showed that VEGF resulted in reduction of CD3+ and CD56+ cells from blood and ascites from cancer patients (Table 1). The expression of VEGF receptors on these cells was low and it was not increased by VEGF. Conclusions: VEGF ascites levels are associated with prognosis in advanced ovarian cancer. Their prognostic significance may be due to the suppression of NK T-like CD3+CD56+ cells. The mechanism of this suppresison remains unclear and it is not through the induction of VEGF receptors on these cells. Total cell counts (×106) in cell cultures with 0, 20, 100 and 500 pg/ml of VEGF Days VEGF 0 pg/ml VEGF 20 pg/ml VEGF 100 pg/ml VEGF 500 pg/ml Healthy (n=3) 0 6 6 6 6 Healthy 7 26.2 24 18 20 Healthy 14 131 122 74.9 106 OvCa blood (n=4) 0 6 6 6 6 OvCa blood 7 10.7 10.8 8 9.2 OvCa blood 14 116 61 66 58 OvCa ascites (n=4) 0 6 6 6 6 OvCa ascites 7 20 12 12 11.5 OvCa ascites 14 150 80 77 60 OvCa: ovarian cancer No significant financial relationships to disclose.
Prognostic significance of circulating tumor cells in bone marrow or peripheral blood detected by qualitative and quantitative PCR in pediatric NPM-ALK positive anaplastic large cell lymphoma
Authors: W. Woessmann, C. Damm-Welk, K. Busch, B. Burkhardt, S. Viehmann, I. Oschlies, W. Klapper, M. Zimmermann, J. Harbott, A. Reiter
Journal: Journal of Clinical Oncology (2007)

9559 Background: Clinical and histopathological characteristics have limited prognostic value for children with anaplastic large cell lymphoma (ALCL). We evaluated the presence, extent and prognostic impact of circulating tumor cells in bone marrow (BM) and peripheral blood (PB) of children and adolescents with NPM-ALK positive ALCL by real-time quantitative PCR for NPM-ALK. Methods: Qualitative and TaqMan-based quantitative PCR assays targeting NPM-ALK were developed with a sensitivity to detect 1 NPM-ALK positive cell among 10 5 cells. Numbers of NPM-ALK transcripts were normalized to 10 4 copies ABL (NCN). BM was analyzed from 80 and PB from 52 German patients registered into the subsequent protocols NHL-BFM95 and ALCL99. Results: BM was positive for NPM-ALK in 47.5% of patients, and positivity was significantly correlated with clinical stage, mediastinal or visceral involvement, microscopic BM involvement, and histological subtype, but not with skin or CNS involvement. Qualitative and quantitative PCR results in BM and PB strongly correlated. BM PCR was associated with the cumulative incidence of relapses (CI-R): CI-R was 50±10% for 38 PCR-positive and 15±7% for 42 PCR-negative patients (p10 NCN NPM-ALK in BM had a CI-R of 71±14% compared to a CI-R of 18±6% for 59 patients with =10 NCN (p10 NCN NPM-ALK in BM, clinical risk factors (skin, mediastinal or visceral involvement) and atypical histological subtype, only &gt;10 NCN NPM-ALK remained a significant poor prognostic factor with a risk ratio of 4.74 (1.57–14.3; p&lt;0.006). Conclusions: The detection of NPM-ALK positive cells by PCR in BM is associated with advanced stage disease, visceral involvement and atypical histology. Quantitative PCR in BM or PB allows identification of 20% of patients experiencing 60% of all relapses with an event-free survival of 20%. No significant financial relationships to disclose.