tbuckley/cabot-search huggingface dataset:
TIE2-expressing myeloid cells as a predictive marker for bevacizumab-containing chemotherapy in metastatic colorectal cancer.
Authors: S. Matsusaka, M. Suenaga, Y. Mishima, K. Takagi, E. Shinozaki, Y. Terui, N. Mizunuma, K. Hatake
Journal: Journal of Clinical Oncology (2011)

e14046 Background: The purpose of this study was to investigate the potential of TIE2-expressing myeloid cells (TEMs) and tumor-associated stroma cells (TASCs) as surrogate markers of clinical outcome in metastatic colorectal cancer patients to identify responders to first-line bevacizumab-containing chemotherapy. Methods: All patients were enrolled using institutional review board-approved protocols at the Cancer Institute Hospital and provided informed consent. The study population consisted of patients of age 18 years or older with metastatic colorectal cancer. Other inclusion criteria were first-line chemotherapy; performance status of 0 or 1; adequate organ function. A total of 51 patients were enrolled in this prospective study. Whole blood samples were analyzed prior to initiation of treatment and on days 4 and 14. TEMs and TASCs were isolated and enumerated using flow cytometry. TEMs (TIE2-positive, CD11b-positive, CD45-positive and VEGFR2-negative fractions) and TASCs (VEGFR2-positive and CD45-positive fractions) were calculated as percentages of the total number of mononuclear cells after evaluation of at least 50,000 cellular events. Results: Patients with ≥6% TEMs at the baseline had the shorter median progression-free survival (PFS; 6.6 months; 95%CI, 5.9-7.4), than the median PFS of <6% TEMs (15.2 months; 95%CI, 10.2-20.2; p<0.001). Patients with ≥6% TEMs at the baseline had the shorter median overall survival (OS), than the median OS of <6% TEMs (p<0.001). In univariate analysis, liver metastasis, lung metastasis, and TEMs at the baseline predicted PFS and OS. In order to evaluate the independent predictive effect of chemotherapy, multivariate Cox regression analysis was carried out. TEMs at the baseline were the strongest predictor. On the other hand, no correlation was observed between levels of TASCs and clinical outcome. Conclusions: TEMs at the baseline were correlated with the prognosis of bevacizumab-containing chemotherapy; therefore this surrogate marker might play a core role in the selection of patients to be candidates for bevacizumab treatment.
Outcomes of definitive chemoradiation for squamous cell carcinoma of the anus and the effect of radiation technique on hematologic parameters.
Authors: C. J. Novak, D. W. Golden, S. L. Liauw
Journal: Journal of Clinical Oncology (2011)

580 Background: Chemotherapy-radiation (CRT) is an established therapy for squamous cell carcinoma of the anus. A limiting factor in the successful completion of CRT is bone marrow toxicity. The effect of intensity modulated radiation therapy (IMRT) on marrow toxicity is not well defined. We evaluated the effect of IMRT on the severity of cytopenias for patients receiving CRT. We also explored the influence of cytopenias on disease outcome both pre-CRT or during CRT. Methods: 43 patients were treated with CRT between 1994-2010. The median delivered dose was 50.4 Gy (range, 32.4-59.4). 31 patients (72%) were treated with IMRT. All patients received concurrent chemotherapy, usually 5FU and mitomycin-C (n = 34, 79%). White blood cell (WBC), hemoglobin (Hg), and platelet counts were recorded pre- CRT, weekly during CRT, and within 7 days post-CRT. Hematologic values were analyzed according to type of RT and for association with treatment outcome. Results: 2-year locoregional failure (LRF) and distant failure were 14% and 14%, respectively. 21 patients required a treatment break due to any cause. In 9 (43%) patients the break was due to hematologic toxicity. 34 patients had complete blood values available. IMRT did not affect the rate of ≥ grade 2 cytopenia (p = 0.64) or median treatment nadirs; Hg (9.1 vs. 8.3 g/dL, p = 0.24), WBC (1.7 vs. 1.2 K/uL, p = 0.95), or platelets (90.5 vs. 61.5 k/uL, p = 0.88). Median time to nadir was not different for WBC (7 vs. 7 days, p = 0.36) or Hg (36 vs. 22 days, p = 0.29), but patients treated with IMRT did have a delayed platelet nadir (33 vs. 14 days, p = 0.01). Hg nadir ≤ 9 g/dL was associated with a higher rate of 2- year LRF (&gt; 9 g/dL 100% vs. ≤ 9 g/dL 73%, p = 0.03). No other hematologic values were associated with LRF. Conclusions: In this cohort of patients, nearly 50% of patients required a treatment break, which was related to a cytopenia 43% of the time. IMRT did not appear to have significant impact on acute marrow toxicity, although sample size may limit our power to detect a difference. Low Hg during CRT appears to influence LRF. More detailed dose volume histogram analysis will be useful to further explore how IMRT might influence acute hematologic toxicity, and therefore treatment outcomes. No significant financial relationships to disclose.
Can trastuzumab enhance the effectiveness of chemotherapy in patients with resected, HER2-positive, stage II/III, or stage IV gastric cancer?
Authors: T. Oshima, C. Kunisaki, S. Fujii, Y. Rino, M. Masuda, T. Imada
Journal: Journal of Clinical Oncology (2011)

e14501 Background: Trastuzumab in combination with chemotherapy has been reported to significantly prolong survival in patients with HER2-positive, unresectable, advanced gastric cancer. However, the therapeutic usefulness of this regimen for surgically resected gastric cancer remains unclear. Adjuvant chemotherapy with S-1 has been shown to be beneficial in patients with stage II or III gastric cancer. Whether trastuzumab should be given to patients with resected, HER2-positive gastric cancer is a very interesting problem. We therefore examined whether trastuzumab can be expected to enhance the effectiveness of chemotherapy in patients with resected, HER2-positive, stage II/III or IV gastric cancer. Methods: The study group comprised 183 patients: 116 had stage II or III gastric cancer and received adjuvant chemotherapy with S-1 after surgery from May 2003 through March 2005; the other 67 had stage IV gastric cancer and sequentially received anticancer agents after surgery from July 1999 through September 2005. HER2 was evaluated by inmmunohistochemistry and FISH according to the protocol of a Study of ToGA. Positive expression of HER2 was defined as a score of 3+ on immunohistochemical staining or as a score of 2+ on immunohistochemical staining plus relative HER2 DNA expression of >2.2 on FISH. Cumulative survival rates were compared between HER2-positive patients and HER2-negative patients. Results: Among patients with stage II or III gastric cancer who received adjuvant chemotherapy with S-1, 20% had HER2-positive tumors; however, cumulative survival rates did not differ significantly between HER2-positive patients and HER2-negative patients. Among patients with stage IV gastric cancer who underwent surgery, 22% had HER2 positive tumors; however, cumulative survival rates did not differ significantly between HER2-positive and HER2-negative patients. Conclusions: The survival benefit of adding trastuzumab to standard chemotherapy was considered minimal in patients with resected, HER2-positive stage II/III or stage IV gastric cancer.
Early outcome results of a phase I/II study for an IL-2/T-cell receptor fusion protein in combination with gemcitabine and cisplatin (GC) in patients with locally advanced or metastatic urothelial cancer.
Authors: Julio Hajdenberg, Danny Landau, Daniel A. Vaena, Mayer N. Fishman, Charles Joel Rosser, Mohammed M. Milhem, Jeffrey S. Weber, Virginia Rizzo, Pamela Zehr, Irene Williams-Elson, Peter Rhode, Tessa Schutt, Liza Hernandez, Bee-Yau Huang, Hing C. Wong
Journal: Journal of Clinical Oncology (2012)

e15010 Background: ALT-801 is a human IL-2/single-chain T-cell receptor fusion protein previously tested in a phase 1 in patients with advanced malignancy (Fishman 2011 CCR 17:7765) (CA097550). In various murine models, ALT-801 demonstrated potent activity against syngeneic and xenograft UC, suggesting sensitivity of this disease to IL-2 based immunotherapy (Wong, unpubl. data.). Although UC are sensitive to platinum-based chemotherapy, combinations such as gemcitabine (G) + cisplatin (C) are associated with CR rates of around 15%, and limited durability of responses with limited effects of retreatment. Methods: We report here initial efficacy results of co-administration of G (1000 mg/m 2 /dose, d 1 &amp; 8), C (70 mg/m 2 /dose, d 1) and ALT-801 (escalating doses, d 3, 5, 8, 10) on a 21 day schedule, for 3 cycles, in patients with UC that was locally advanced, or metastatic, for whom GC chemotherapy would be considered. ALT-801 planned doses are 0.04 to 0.12 mg/kg/dose in 5 dose cohorts with a 3+3 escalation design. Subjects with at least stable disease after 3 courses may receive 4 additional weekly doses of ALT-801 alone. Results: To date, three Stage IV UC patients (1F, 2M; 59-63 yrs; 2 patients had predominantly nodal metastases and one patient liver metastases) completed treatment with 0.04 mg/kg ALT-801+GC. Two had previously undergone radical cystectomy and had then later failed following GC treatment. Grade 3/4 toxicities observed include neutropenia (2), thrombocytopenia (2), leukopenia (1), lymphopenia (1) and anemia (1), consistent with GC and ALT-801 known pharmacodynamic effects. All 3 had radiological CRs by week 13. One patient underwent radical cystectomy had a pCR. The next (0.06 mg/kg/dose) cohort has started treatment. A phase II expansion cohort is planned at the MTD. Conclusions: The early response pattern is encouraging in that ALT-801 may be a novel, active immunotherapy for UC. NCT01326871
Perioperative chemotherapy plus bevacizumab with early salvage therapy based on PET response in patients with locally advanced resectable gastric/GEJ cancer.
Authors: E. C. Smyth, H. Schöder, D. G. Coit, V. E. Strong, M. F. Brennan, Y. Y. Janjigian, M. Capanu, L. H. Tang, D. P. Kelsen, M. A. Shah
Journal: Journal of Clinical Oncology (2010)

TPS200 Background: A standard of care for locally advanced resectable gastric or (GE) junction cancer is perioperative chemotherapy (CT) as per the MAGIC trial (Cunningham NEJM 2006). Bevacizumab (bev) plus CT has demonstrated improved efficacy in metastatic gastric cancer (Shah 2006). Fluorodeoxyglucose (FDG) PET identifies metabolic poor responders following a single cycle of CT and PET nonresponse is strongly correlated with poor histologic response and inferior survival, whether the patient (pt) proceeds directly to surgery or continues with the initial CT (Ott JCO 2006, Lordick Lancet Oncol 2007). This phase II trial seeks to improve the efficacy of perioperative chemotherapy by combining CT with bev, and by using an early PET scan to identify non-responding pts and switching to non-cross-resistant CT. Methods: This is a single institution nonrandomized phase II trial. Eligible pts include those with resectable GE junction or gastric cancers which are FDG avid (tumor SUV > 3.5 or a tumor:liver ratio > 1.5) and have received no prior treatment for their disease. Pts receive on day 1 CT with epirubicin 50 mg/m2 iv, cisplatin 60 mg/m2 iv or oxaliplatin 130 mg/m2 iv and fluorouracil (200 mg/m2/day via continuous infusion or capecitabine 625 mg/m2/day days 2-21), plus bev 15 mg/kg iv. CT is stopped 48 hours prior to repeat PET on day 18-21. Pts with a good metabolic response (>35% decrease in FDG uptake) at repeat PET proceed with 2 further cycles of the initial CT with bev given on cycle 2 only. PET nonresponders switch to salvage docetaxel 30 mg/m2 d1, d8 q21 days, irinotecan 50 mg/m2 d1, d8 q21 days and bev 15 mg/kg d1, cycle 2 only. Postoperatively, pts continue on the CT regimen they received prior to surgery for 3 cycles. The primary endpoint is to assess the benefit of early PET directed change to salvage CT in a non-PET responding pts in terms of improved disease free survival at 2 years. Secondary endpoints include response rate, efficacy and safety of bev plus CT in the all study pts. Biological correlates include circulating tumor cells and DNA microarray assessment of gene expression correlating to treatment response. Estimated sample size is 60 pts, with 11 accrued to date. No significant financial relationships to disclose.
Single tunneling method with endoscopic submucosal dissection for treatment of a rectal giant (18-cm) laterally spreading tumor
Authors: Fatih Aslan, Zehra Akpinar, Derya Yurtlu, Melek Kucuk, Nese Ekinci, Belkis Unsal
Journal: Endoscopy (2017)

Endoscopic submucosal dissection (ESD) is an effective method for en bloc complete resection of lesions. We report a case of an 18-cm laterally spreading tumor (LST) in the colon that was successfully removed by colorectal ESD using a tunneling technique.
Prognostic value of the number of retrieved lymph node and lymph node ratio in locally advanced rectal cancer after preoperative radiation therapy.
Authors: Jin-hong Park, Young Seob Shin, Eun Kyung Choi, Seung Do Ahn, Sang Min Yoon, Jong Hoon Kim
Journal: Journal of Clinical Oncology (2014)

582 Background: To assess the prognostic impact of total number of retrieved lymph node (TNN) and lymph node radio (LNR) in patients with locally advanced rectal cancer who received preoperative radiation therapy and surgery Methods: We retrospectively analyzed data from 677 patients with locally advanced rectal cancer who underwent preoperative radiation therapy followed by mesorectal excision at Asan Medical Center between October 1999 and May 2009. The median radiation dose was 50 Gy, and 674 patients (99%) underwent concurrent chemotherapy. All patients were divided into two groups according to the status of lymph node involvement. We assessed the influence of TNN on overall survival (OS) and disease-free survival (DFS) in the patients with node-negative disease (pN0, n = 490), and the prognostic value of LNR, estimated by dividing the number of positive nodes by the number of lymph nodes examined, in the patients with node-positive disease (pN1-2, n = 187). Results: The median follow-up period was 74 months.Patients with pN0 had median 12 lymph nodes examined (range, 0-38). Comparing with patients who had ≤ 8 TNN, patients with &gt; 9 TNN had significantly higher 5-year OS (89% vs. 95%, p = 0.038) and DFS rates (81% vs. 90%, p = 0.013). Multivariate analysis showed that TNN more than 9 was significant prognostic factor for OS (p = 0.032) and DFS (p = 0.007). For patients with pN1-2, patients with low LNR (≤ 0.33, n = 144) showed significantly higher 5-year OS (33% vs. 73%, p &lt; 0.001) and DFS rates (18% vs. 56%, p &lt; 0.001) than high LNR group (&gt; 0.33, n = 43). Also, low LNR was independent prognostic factor for OS (p = 0.001) and DFS (p &lt; 0.001) in multivariate analysis. Conclusions: TNN for node-negative rectal cancer and LNR for node-positive rectal cancer are independent prognostic factors for survival outcome in patients with locally advanced rectal cancer after preoperative radiation therapy. These factors could be considered as useful prognostic indicators irrespective of current TNM staging system.
Use of high-cost imaging in elderly patients with metastatic cancer.
Authors: Y. Hu, A. C. Kwok, W. Jiang, N. Taback, S. R. Lipsitz, G. V. Ting, E. T. Loggers, J. C. Weeks, C. C. Greenberg
Journal: Journal of Clinical Oncology (2011)

6112 Background: Diagnostic imaging is Medicare’s most rapidly growing service, and increasing rates of imaging have been documented among cancer patients. Like all interventions in patients with metastatic solid tumors, imaging may contribute to palliation but is unlikely to lead to long-term survival. We sought to determine patterns of imaging use in this population and to compare temporal trends with those observed among patients with curable early-stage disease. Methods: We extracted SEER-Medicare claims dated 1999-2007 for patients diagnosed with stage IV breast, colorectal, lung, or prostate cancer in 2000-2005 (n=64,267). High-cost imaging procedures were identified by CPT and/or ICD-9 codes for CT, MRI, PET, and nuclear medicine (NM) studies. Summary statistics were calculated, including percent of patients imaged and number of imaging procedures per patient. Comparable data were generated for patients with stage I-II disease of the same tumor types (n=127,827). Mean rates between groups were compared using the Wilcoxon test. We grouped patients according to year of diagnosis and compared utilization rates for the first and last year of the study period. Results: Stage IV patients underwent a mean of 2.4 high cost imaging procedures during the 60 day diagnostic period, compared to 0.8 in early stage patients (p<0.0001). Thereafter, stage IV patients underwent 0.7 high cost scans per month (1 scan every 43 days on average). 41% of stage IV patients were imaged in the last month of life. Over time, overall utilization increased in stage IV patients, while use decreased in early stage patients (Table). Conclusions: Patients with stage IV solid tumors undergo frequent high cost imaging. Imaging rates in this population are increasing over time, in contrast to the observed decrease in those with curable disease. There is an urgent need for studies to determine whether the benefits of these procedures justify the cost, measured in societal resources as well as patient discomfort and anxiety. Percent of patients imaged by year of diagnosis. 2000 2005 Change Stage I-II Any CT MRI PET NM 94% 86% 45% 11% 66% 87% 71% 32% 15% 60% −7% −15% −13% +4% −6% Stage IV Any CT MRI PET NM 94% 91% 39% 6% 62% 97% 94% 47% 32% 55% +3% +3% +8% +26% −7%
Phase II trial of gefitinib in Chinese female patients with advanced non-small cell lung cancer.
Authors: J. Deng, W. J. Fang, X. C. Zhang, J. Chen, J. Qian, H. B. Mou, N. Xu
Journal: Journal of Clinical Oncology (2011)

e18066 Background: Non-small cell lung cancer (NSCLC) in women is a unique entity worthy of in-depth study. Here we performed a phase II clinical trial to evaluate the efficacy and safety of gefitinib on pretreated Chinese female non-small cell lung cancer (NSCLC) patients. And further we tried to elucidate the correlation of EGFR mutations with the tumor response and the survival. Methods: Chinese female patients with locally advanced or metastatic NSCLC who failed at least one platinum-based chemotherapy received gefitinib monotherapy (250mg/d) between April 2002 and January 2010. Tumor evaluation by RECIST criteria was scheduled every 8 weeks. Progression-free survival (PFS) and overall survival (OS) was calculated and a Cox regression model was used to identify factors that potentially affect survival and overall response rate (ORR). Epidermal growth factor receptor (EGFR) gene mutations were investigated on diagnostic biopsy tissue by direct gene sequencing of exons 18 to 21 of chromosome 7 and correlated with ORR, PFS and OS. Results: Of the 40 evaluable female patients, the ORR was 62.5%. All patients have responded with one (2.5%) complete response, 24(60%) partial response, 12 (30%) stable disease, and 3 (7.5%) progressive disease. The OS and PFS were 20 months (95% CI: 11.9-28 months) and 13 months (95% CI: 8.0-17.9 months), respectively. Survival (OS and PFS) were longer in patients with good performance status and in patients older than 65 years (P<0.05). The most frequently observed toxicities were rash/dry skin (80%), diarrhea (42.5%) and vomiting/anorexia (32.5%). Four patients developed grade 3 toxicities (rash and diarrhea) but did not require either dose reduction or discontinuation. Conclusions: Gefitinib is a highly effective and well-tolerated agent for Chinese women with pretreated advanced NSCLC. Biomarker evaluation of EGFR mutation analysis is ongoing.
Validation of the survival benefit from metformin use in patients with type 2 diabetes and colorectal cancer.
Authors: Ibrahim Halil Sahin, Hesham Mohamed Hassabo, Yehua Shen, Bryan K. Kee, Manal Hassan, Chris R. Garrett
Journal: Journal of Clinical Oncology (2013)

462 Background: We previously reported improved overall survival (OS) associated with metformin usage in a retrospective study of type 2 diabetes mellitus (DM) patients with colorectal (CRC) (Br J Cancer 2012;106:1374-8). We sought to determine whether this effect could be validated in an independent data set. Methods: Under an IRB-approved protocol, 6,128 patients with CRC based on ICD-9 billing codes diagnosed between 1995-2005 were reviewed; of these 683 were determined to have type 2 DM. Results: Of the 683 diabetic CRC patients, 407 (59.5%) were male. The patient’s stage at diagnosis was: stage I (67, 9.8%), II (162, 23.7%), III (247, 36.1%), IV (166, 24.3%) and unknown stage (41, 6%). The number of patients using metformin at the time of first evaluation was 146 (21.3%). A significantly better median OS was observed in CRC patients with metformin use in both all-stage and stage III groups (p = 0.017, p = 0.029 respectively); median OS results demonstrated in table below. Conclusions: This independent retrospective data set validated the OS benefit associated with metformin use previously reported in patients with type 2 DM and CRC. Future prospective studies will be required to confirm the benefit of metformin in this clinical setting. [Table: see text]
Improving chemotherapy consent compliance.
Authors: Patricia D. Hegedus, James D. Bearden, Bruce Grant
Journal: Journal of Clinical Oncology (2012)

130 Background: Palmetto Hematology Oncology (PHO) is the medical oncology practice of Spartanburg Regional Healthcare System (SRHS) and has participated in QOPI since 2009 and earned QOPI certification in September 2011. Our Fall 2010 QOPI Patient Consent for Chemotherapy score was 70.73%, lower than the QOPI aggregate score of 86.46%. Methods: A workgroup was convened to address chemotherapy consent documentation compliance. QOPI data revealed the need for a uniform, system-wide chemotherapy consent process. A chemotherapy consent form specifically for our cancer center was created following an extensive literature review and benchmarking with American Society of Clinical Oncology guidelines, NCI Designated Cancer Centers, NCI Community Cancer Centers Program (NCCCP funded with federal funds from the NCI, Contract # HHSN261200800001E) resources, and other healthcare institutions. Our chemotherapy administration policy was revised to include a “hard stop” if a signed chemotherapy consent was not available prior to administration of chemotherapy in all areas of our institution. Results: Patient Consent for Chemotherapy QOPI scores revealed an increase from Fall 2010 to Spring 2012 of 70.73% to 100%. As a result of the workgroup’s efforts, it was approved by our Cancer Care Committee to develop a Chemotherapy Safety Committee (CSC) to standardize chemotherapy practices throughout our system. The CSC integrated key staff responsible for chemotherapy administration. The CSC was instrumental in reviewing and updating policies and procedures during our QOPI certification efforts. Conclusions: Our participation in QOPI provided data to support efforts for a system-wide chemotherapy consent revision and process implementation. The availability of ASCO, Oncology Nursing Society, and other key resources provided turn key processes for this performance improvement project. Practice scores for the Patient Consent for Chemotherapy have reached 100% compliance signifying our performance at a “best practice” level. References: QOPI The Quality Oncology Practice Initiative, available at: http://qopi.asco.org/program .
Identification and Validation of HLA-A24 XBP1us, XBP1sp, CD138, and CS1 Peptides to Generate Antigens Specific-Cytotoxic T Lymphocytes: Preclinical Basis for Vaccine Therapy in HLA-A24 Patients with Multiple Myeloma and Other Cancers
Authors: Jooeun Bae, Brandon Nguyen, Matthew Ho, Yan Song, Noopur Raje, Paul G. Richardson, Teru Hideshima, Dharminder Chauhan, Nikhil C. Munshi, Kenneth C. Anderson
Journal: Blood (2016)