tbuckley/cabot-search huggingface dataset:
Concurrent administration of weekly trastuzumab and adjuvant breast radiotherapy increases skin, esophageal, and cardiac acute toxicities
Authors: Y. Belkacemi, J. Gligorov, H. Laharie-Mineur, H. Marsiglia, M. Ozsahin, D. Azria
Journal: Journal of Clinical Oncology (2006)

630 Background: Trastuzumab (T) combined with chemotherapy (CT) has been recently shown to improve the outcome in patients with HER2-positive breast cancer. Its administration either weekly or every 3 weeks for one year is recommended as adjuvant therapy. Nevertheless, little is known about the toxicity of radiotherapy (RT) and T administered concurrently. Methods: Since June 2005, 95 patients (pts) with stage II-III HER2-positive breast cancer were treated concurrently with adjuvant T and RT. At this time, 53 have completed their combined therapy. Median age was 48y and 22 pts were menopausal. Twelve and 41 pts received T weekly or every 3 weeks, respectively. Neoadjuvant CT using anthracyclin/taxane regimen was administered in 27 pts. T was initiated after the last cycle of anthracyclin. Hormonal treatment was given to 17 hormone-receptor positive pts. RT was delivered to the whole breast (45–50 Gy ± a 10 to 16 Gy-boost, n=24) or to the chest wall (50 Gy, n=29). Internal mammary chain (IMC) and supraclavicular nodes were irradiated in 41 pts. Toxicity assessment (dermatitis, esophagitis and left ventricular dysfunction) was implemented according to the CTC v3.0 criteria. Results: Grade (G) 2 or more skin and esophageal toxicities were observed in 27/53 (51%) and 7/53 (13%) pts, respectively. Post-RT left ventricular dysfunction was observed in 22 pts (G1 in 14, G2 in 6, and G3 in 2). In univariate analyses, unfavorable factors influencing G2 or more cardiac toxicity were postmenopausal status (p=0.03), IMC irradiation (p=0.005) and weekly T administration (p=0.0001). Multivariate analysis revealed the concurrent administration of weekly T and RT (WTRT) as an unfavorable independent prognostic factor for cardiac toxicity (p=0.0001) and for G2 or more dermatitis (p=0.05). The two unfavorable prognostic factors for esophagitis (G2 or more) were concurrent administration of WTRT (p=0.008) and total mastectomy (p=0.004). Conclusion: Our preliminary results show that in addition to increased skin and esophageal acute toxicities, concurrent administration of weekly T and RT significantly decreases the left ventricular ejection fraction compared to the 3-week schedule. Results for the whole cohort will be presented at the meeting. No significant financial relationships to disclose.
First Line Treatment with Bendamustine in Selected Non Hodgkin's Lymphoma Patients: Prospective Experience in Tuscany Region
Authors: Luigi Rigacci, Benedetta Puccini, Roberta Della Seta, Enrico Capochiani, Lorenzo Iovino, Emanuele Cencini, Paolo Bernardeschi, Sofia Kovalchuk, Gemma Benelli, Silvia Birtolo, Mario Petrini, Alberto Fabbri, Alberto Bosi
Journal: Blood (2014)
A phase I study assessing the feasibility and safety of intraductal pegylated liposomal doxorubicin (PLD) in women with breast cancer
Authors: L. K. Jacobs, N. Khouri, S. Jeter, P. Powers, M. Rudek, E. Gabrielson, Z. Zhang, S. Sukumar, T. Tsangaris, V. Stearns
Journal: Journal of Clinical Oncology (2009)

e11506 Background: Most breast cancers originate in epithelial cells lining the breast ducts. Preclinical data suggest that intraductal administration of chemotherapy including PLD decrease tumor volume, prevent the development of new lesions, and eradicate pre-malignant disease. We initiated a clinical trial to determine the feasibility, safety, and maximum tolerated dose of PLD administered into one duct of women awaiting mastectomy. Methods: Women 18 or older awaiting mastectomy for breast cancer were eligible. Preoperative chemotherapy was allowed. T4 tumors, prior breast irradiation, or surgeries that may have altered the ductal system were excluded. Nipple aspiration and ductal cannulation were completed and the first 3 women received 5 mL of intraductal dextrose. PLD was administered to subsequent participants on a dose escalation schema based on preclinical pharmacokinetic and safety data. Serial doxorubicin (Dox) and doxorubicinol (Doxol) concentrations were determined in plasma by LC/MS/MS. At mastectomy (completed at least 2 weeks after intraductal administration of PLD), blue dye was injected into the treated duct and tissue was obtained for pharmacokinetic and biomarker analysis. Results: From 2/06 to 6/08, 14 women enrolled, and 12 underwent all study procedures. All dose levels up to 10 mg PLD per one duct were completed without serious adverse events. Median pain score was 0.9 (0–2.3). Intraductal PLD resulted in a dose-dependent increase in both systemic and local exposure to dox and doxol. Neither dox nor the metabolite was detected in the contralateral breast. Systemic exposure was lower than with conventionally administered PLD. Inflammatory changes were not observed on histopathological review of mastectomy specimens. Conclusions: We have established the logistics of intraductal administration of agents in an outpatient setting and it is feasible in women with and without prior chemotherapy. Biomarker data will be completed prior to the meeting. Future studies will evaluate other agents administered to one or more ducts. [Table: see text]
Afatinib-Induced Severe Interstitial Lung Disease Successfully Treated with High-Dose Corticosteroid Therapy: A Case Report
Authors: Kazutaka Fujita, Yuko Morishima, Yuka Aida, Yoshiya Tsunoda, Norihito Hida, Toshihiro Shiozawa, Kensuke Nakazawa, Ikuo Sekine, Nobuyuki Hizawa
Journal: Journal of Thoracic Oncology (2016)
Concurrent intrathecal methotrexate and radiotherapy for the treatment of leptomeningeal metastases from solid tumors with adverse prognostic factors: A prospective, single-arm, and open-label study.
Authors: Zhenyu Pan, Guozi Yang, Yu Li, Lihua Dong, Weiyan Shi, Tingting Yuan, Yongxiang Wang
Journal: Journal of Clinical Oncology (2015)

e20556 Background: The prognosis of leptomeningeal metastases (LM) from solid tumors is extremely poor, especially for patients with adverse prognostic factors. Previous studies indicate that intrathecal chemotherapy (IC) does not improve overall survival (OS) for patients with adverse prognostic factors. Involved-field radiotherapy (IFRT) alone only alleviates symptoms of the nervous system with no survival benefit. This study investigated IC in combination with IFRT for the treatment of LM from solid tumorswith adverse prognostic factors to assess therapeutic response, toxicity and OS. Methods: Fifty-three patients with LM from solid tumors were enrolled between September 2010 and May 2014. The treatment regimen was concurrent IC (MTX 12.5-15 mg and dexamethasone 5 mg, weekly) and IFRT (whole brain RT 40 Gy/20 f and/or spinal RT 40-50 Gy/20-25 f). Induction IC for 1-3 times was given followed by concurrent therapy for patients with low KPS score as well as intolerance to radiotherapy. All patients were followed up until October 2014. The evaluation of therapeutic response was according to the improvement of nervous system symptoms and KPS score. Results: The pathological types included non-small cell lung cancer (26), small cell lung cancer (10), breast cancer (11), gastric cancer (3) and others (3). Median KPS score was 40 (range 20-70). Most patients (84.9%) completed the concurrent therapy. The overall response rate was 84.9%. Forty-three patients were dead by the end of follow-up. Survival ranged from 0.4 to 26.7 months (median 6.5). The treatment-related adverse events consisted mainly of acute meningitis, chronic delayed encephalopathy, radiculitis, myelosuppression and mucositis. Eight patients (15.1%) had grade III-IV toxicities. Three patients (5.7%) died of neurotoxicity at 1.5, 5.5 and 7.1 months after concurrent therapy, respectively. Conclusions: The regimen of concurrent therapy with significant activity and acceptable toxicity may be an optimal therapeutic option for treatment of LM from solid tumors with adverse prognostic factors. Clinical trial information: ChiCTR-OOC-14005403.
Gene Signatures Predictive of Outcome in Higher Risk Childhood Acute Lymphoblastic Leukemia (ALL).
Authors: Naomi P. Moskowitz, Deepa Bhojwani, Huining Kang, Dong-Joon Min, Jeffrey Potter, Richard Harvey, Nita L. Seibel, Elizabeth Raetz, Harland N. Sather, Stephen P. Hunger, Cheryl L. Willman, William L. Carroll
Journal: Blood (2005)
Hematopoietic Transdifferentiation of Muscle-Derived Cells after In Vivo Transient Expression of MSX1 Transcription Factor.
Authors: Masaharu Nobuyoshi, Akihiro Kume, Hiroaki Mizukami, Takashi Matsushita, Takashi Okada, Masashi Urabe, Yuichi Ohgoshi, Takashi Endo, Keiya Ozawa
Journal: Blood (2004)
Abstract C21: IL-33 promotes growth and liver metastasis of colorectal cancer in mice by remodeling the tumor microenvironment and inducing angiogenesis
Authors: Maria Marjorette O. Pena, Yu Zhang, Celestia Davis, James C. Ryan, Diego Altomare, Sapana Shah, Daniel Titus Hughes
Journal: Cancer Research (2016)

Abstract The major cause of death from colorectal cancer (CRC) is liver metastasis and understanding its mechanisms is necessary for early diagnosis and development of new therapies. Interleukin-33 (IL-33) is an IL-1 cytokine that functions as a cytokine and nuclear factor. It is released by necrotic epithelial cells and activated innate immune cells, functioning as an alarmin or early danger signal. Its role in invoking type 2 immune response is firmly established; however, its role in tumor development and metastasis in only beginning to be elucidated. We identified IL-33 as a potently upregulated cytokine in highly metastatic CRC cells and examined its role in tumor growth and metastasis to the liver. We expressed IL-33 in murine and human CRC cell lines and their growth and spontaneous metastasis to the liver was assessed in orthotopic models of CRC in wild type and IL33 knockout mice. The results suggest that tumor- rather than host- derived IL-33 promoted growth and metastasis by inducing expression of cytokines that stimulated mobilization of CD11b+ GR1+ and CD11b+F4/80+ myeloid cells to remodel the tumor microenvironment, and increase tumor angiogenesis, potentially by activating endothelial cells. Conversely, pro-tumorigenic cytokines derived from the microenvironment induced IL-33 expression in tumor cells to create a sustained pro-tumorigenic loop that promotes tumor growth and metastasis. Our findings underscore the potential of IL-33 as a novel and viable therapeutic target for CRC and liver metastasis. Citation Format: Maria Marjorette O. Pena, Yu Zhang, Celestia Davis, James C. Ryan, Diego Altomare, Sapana Shah, Daniel Titus Hughes. IL-33 promotes growth and liver metastasis of colorectal cancer in mice by remodeling the tumor microenvironment and inducing angiogenesis. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr C21.
Human liver sinusoidal endothelial cells promote intracellular crawling of lymphocytes during recruitment: A new step in migration
Authors: Daniel A. Patten, Garrick K. Wilson, Dalan Bailey, Robert K. Shaw, Sirpa Jalkanen, Marko Salmi, Antal Rot, Chris J. Weston, David H. Adams, Shishir Shetty
Journal: Hepatology (2016)

The recruitment of lymphocytes via the hepatic sinusoidal channels and positioning within liver tissue is a critical event in the development and persistence of chronic inflammatory liver diseases. The hepatic sinusoid is a unique vascular bed lined by hepatic sinusoidal endothelial cells (HSECs), a functionally and phenotypically distinct subpopulation of endothelial cells. Using flow-based adhesion assays to study the migration of lymphocytes across primary human HSECs, we found that lymphocytes enter into HSECs, confirmed by electron microscopy demonstrating clear intracellular localization of lymphocytes in vitro and by studies in human liver tissues. Stimulation by interferon-γ increased intracellular localization of lymphocytes within HSECs. Furthermore, using confocal imaging and time-lapse recordings, we demonstrated "intracellular crawling" of lymphocytes entering into one endothelial cell from another. This required the expression of intracellular adhesion molecule-1 and stabilin-1 and was facilitated by the junctional complexes between HSECs. Conclusion: Lymphocyte migration is facilitated by the unique structure of HSECs. Intracellular crawling may contribute to optimal lymphocyte positioning in liver tissue during chronic hepatitis. (Hepatology 2017;65:294-309).
A phase I study of pegylated doxorubicin (DOX) and weekly topotecan (TOP) in patients (pts) with advanced solid tumors
Authors: G. A. Masters, M. Guarino, C. Schneider, D. Biggs, S. Grubbs
Journal: Journal of Clinical Oncology (2006)

12018 Background: The primary endpoint of this prospective phase I study of DOX-TOP in pts with advanced solid tumors was to identify the maximum tolerated dose and dose-limiting toxicities (DLT) of this combination. Other objectives included a description of additional toxicities and efficacy in this patient population with refractory cancers. Pharmacokinetic sampling of TOP plasma levels will be reported separately. Methods: Eligible pts had advanced solid tumors and had either failed standard chemotherapy (chemo) or were pts for whom no standard therapy existed. They had ECOG PS = 0–2, adequate organ function, and gave written, informed consent. Initial doses included DOX 40 mg/m 2 day 1 and TOP 2 mg/m 2 days 1, 8 and 15 q 28 days. TOP was to be escalated in cohorts of pts. DLT was defined as febrile neutropenia, grade 4 thrombocytopenia, any grade 3 non-hematologic toxicity, or the inability to receive subsequent treatment due to ongoing toxicity. Treatment was held for ANC &lt; 1000 or platelets &lt; 75,000. Results: Fourteen pts have been enrolled on this phase I study, all of whom were evaluable for toxicity. There were 12 males and 2 females, and the median age was 57 years (range 25–86). Four had ECOG PS = 0, 9 had PS = 1, and 1 had PS = 2. Cancer types included head and neck (3), renal (2), and breast, pancreas, liver, esophagus, germ cell tumor, sarcoma, and others (one each). In the 6 pts treated at dose level 1, toxicities included grade 3 anemia (1) and neutropenia (2), and grade 4 neutropenia (1). DLT consisted of grade 4 thrombocytopenia (1) and inability to deliver day 15 TOP in 3/6 pts at this dose. Thus, TOP was reduced to 1.5 mg/m 2 weekly for dose level -1, and 8 pts have been treated. Toxicities included grade 3 anemia (1)and neutropenia (2), and grade 4 neutropenia (1) and thrombocytopenia (1). Enrollment continues at this dose level to confirm tolerability. No patient achieved an objective response to therapy, but 2 pts have stable disease for up to 4 cycles. Conclusions: DOX-TOP can be safely combined in pts with advanced solid tumors, with hematologic toxicity as the DLT. The preliminary recommended phase II dose is DOX 40 mg/m 2 and TOP 1.5 mg/m 2 . We plan to explore an additional dose level of DOX 30 mg/m 2 and TOP 2 mg/m 2 . Phase II evaluation is contemplated in selected tumor types. [Table: see text]
Case 32-2016
Authors: Shannon M. MacDonald, Otto Rapalino, Nicole A. Sherry, Adam B. Cohen, David H. Ebb, Nancy J. Tarbell, Derek H. Oakley
Journal: New England Journal of Medicine (2016)

A 20-year-old man reported a 3-year history of gynecomastia and a 4-year history of polyuria and polydipsia that had recently resolved. Evaluation revealed bilateral gynecomastia, minimal facial hair, small testes, and an elevated serum sodium level. Diagnostic tests were performed.
BMET-15TUMOR CELL FREE DNA IN CEREBRAL SPINAL FLUID REFLECTS TREATMENT RESPONSE IN LEPTOMENINGEAL METASTASIS
Authors: Yingmei Li, Wenying Pan, Ian Connolly, Seema Nagpal, Sunil Reddy, Stephen Quake, Melanie Hayden Gephart
Journal: Neuro-Oncology (2015)

Cerebral Spinal Fluid (CSF) from brain tumor patients contains tumor cell free DNA (cfDNA), which may provide a non-invasive and routinely accessible method to obtain tumor genomic information.This "liquid biopsy" method would prove considerably less morbid compared to an open removal of tumor tissue from the brain.The opportunities of cfDNA in CSF
Effects of reduced glutathione (GSH) on oxaliplatin pharmacokinetics (OXA pk) and on Pt-DNA adducts formation in advanced colorectal cancer patients treated by FOLFOX4 regimen
Authors: C. Zanon, M. Airoldi, R. Passera, L. Cattel, P. Milla, U. Jaehde, A. Drescher, L. Branciforte, I. Gozzelino, F. Pedani
Journal: Journal of Clinical Oncology (2007)

2559 Background: Neurotoxicity is a common OXA toxicity in FOLFOX4 regimen for patients with advanced colorectal cancer. Recently, Cascinu et al. (JCO 2002; 20: 3478–3483) provided evidence that GSH reduces the OXA-induced neurotoxicity, but GSH influence on the formation of Pt-DNA adducts still remains unknown. This study evaluated the effect of GSH addition on OXA pk and on Pt-DNA adducts formation Table of Contents Methods: 28 patients were given twelve FOLFOX4 courses and randomized to receive either GSH 1,500 mg/m 2 or normal saline solution (placebo) before OXA iv infusion. OXA pk and Pt-DNA adducts formation were evaluated at courses 5, 9 and 12. Total and ultrafiltered platinum were analyzed by atomic adsorption, Pt-DNA adducts in leukocytes (as model for tumour tissue) by adsorptive stripping voltammetry. Pk analysis were done by non-compartmental analysis, statistical analysis by non-parametric Mann-Whitney test. Results: Median total and ultrafiltered platinum median C max and AUC tot values were comparable to previously reported ones, being higher in the placebo arm, due to a moderate reduction of platinum clearance. The formation of Pt-DNA adducts was more pronounced in GSH arm (median value 20.3 Pt atoms/10 6 nucleotides vs. 5.7 Pt atoms/10 6 nucleotides), even not statistically significant. Conclusions: The addition of GSH to FOLFOX4 regimen is able to reduce the OXA-induced neurotoxicity, without affecting either the OXA pk behaviour or the formation of Pt-DNA adducts, without modifying FOLFOX4 clinical efficacy. [Table: see text] No significant financial relationships to disclose.
Low expression of bax predicts poor prognosis in patients with locally advanced esophageal cancer treated with definitive chemoradiotherapy
Authors: S. Kang, J. Han, K. Lee, J. Choi, J. Park, H. Lee, H. Kim, J. Kim, S. Kang, Y. Oh, S. Sheen
Journal: Journal of Clinical Oncology (2007)

4597 Background: The present study evaluated the prognostic significance of apoptosis-related proteins, p53, bcl-2, bax, and galectin-3 in patients with locally advanced esophageal cancer treated with definitive chemoradiotherapy (CRT). Methods: Sixty-three patients with locally advanced esophageal cancer (stage II-IV) were treated with definitive CRT using 5-fluorouracil and cisplatin combined with radiotherapy. Pretreatment tumor biopsy specimens were analyzed for p53, bcl-2, bax, and galectin-3 expression by immunohistochemistry. Results: High expression of bax, p53, bcl-2, and galectin-3 was observed in 67%, 47%, 24%, and 29% of patients, respectively. The median overall survival (OS) of total patients was 14 months with 16% of 3-year OS. High expression of p53, bcl- 2, and galectin-3 did not demonstrate correlation with clinicopathologic characteristics, including patient outcome. Low expression of bax was significantly correlated with clinical complete response (p=0.023). Low expression of bax was also associated with poor OS (median, 8 months vs. 16 months; P=0.0008) in univariate analysis. In multivariate analysis, low expression of bax was the most significant independent predictor of poor OS (p=0.01) followed by clinical complete response and low radiation dose. Conclusions: Low expression of bax was significantly associated with the poor survival of patients with locally advanced esophageal cancer treated with CRT using 5-fluorouracil and cisplatin. Immunohistochemical staining for bax with a pretreatment biopsy specimen might be useful to select the optimal treatment options for these patients. No significant financial relationships to disclose.
Prognostic factors in advanced seminoma in the era of etoposide- and cisplatin-based chemotherapy: Importance of pretreatment LDH-level
Authors: A. Tryakin, M. Fedyanin, A. Bulanov, D. Titov, G. Allakhverdiyeva, A. Mitin, J. Sergeev, T. Zaharova, A. Garin, S. Tjulandin
Journal: Journal of Clinical Oncology (2009)

e16038 Background: The commonly used IGCCCG classification probably underestimates other prognostic factors (tumor markers, stage) for advanced seminoma, which was shown later (Fossa S., 1997). Furthermore, in contrast to nonseminoma different cisplatin-based regimens have not been directly compared in this population. We performed an analysis to review the outcome and prognostic factors of patients (pts) with advanced seminoma treated in our center during the last two decades. Methods: From 1983 to 2005, 250 chemotherapy (CT)-naïve pts with advanced seminoma received induction platinum-based CT, which was divided as an “older” (76 pts) and “modern” (174 pts) one. “Older CT” included cyclophosphamide + cisplatin (46 pts), ifosfamide + carboplatin (12 pts), PVB (8 pts) and other regimens (10 pts). “Modern CT” contained BEP (26 pts) and EP (148 pts) regimens. 227 (91%) pts had primary testicular tumor, 241 (96%) pts belonged to IGCCCG good prognostic group. Median follow-up was 57 (range, 3–276) months for the pts who survived. Prognostic factors were analyzed in “modern CT” group. Progression-free survival (PFS) was an end-point for Cox‘ stepwise regression analysis. Results: “Modern CT” significantly improved PFS (5-years, 91% and 74%, p = 0.002) but not OS (5-years, 92% and 89%, p = 0.28), which could be explained by effective salvage CT. Univariate analysis revealed following factors as significant: number of metastatic sites, presence of pulmonary metastases, RPLN size, hCG level, and LDH level. Cox‘ regression analysis showed pre-CT LDH as the only prognostic factor for PFS (HR 7,6, 95% CI 1,6–36.3). Using cut-off 2 x upper limit of normal for LDH level, “modern CT” group can be divided into favorable (105 [60%] pts) and unfavorable (69 (40%) pts) groups with 5-years DFS 98% vs. 78% (HR 11.1, 95% CI 3.2–33.3) and 5-years OS 99% vs. 80% (HR 11.07, 95% CI 3.09–27.92), respectively. Conclusions: Comparing with older cisplatin-based regimens, the new ones (BEP or EP) improved PFS without significant influence on OS in pts with advanced seminoma. Pre-treatment LDH level is an important independent prognostic factor, which could help stratify pts better into risk groups. Further studies with risk-adapted policy in advanced seminoma are warranted. No significant financial relationships to disclose.
Sequencing of Subcloned PCR Products Facilitates Earlier Detection of BCR-ABL1T315I Mutants Compared to Direct Sequencing of the ABL1 Kinase Domain.
Authors: Alfonso Quintás-Cardama, Don L. Gibbons, Hagop Kantarjian, Moshe Talpaz, Nicholas Donato, Jorge Cortes
Journal: Blood (2007)
Reduced Effect of Inotuzumab Ozogamicin (CMC544) on P-Glycoprotein Positive Malignant B Cells and Its Restoration by Multidrug Resistance Modifiers.
Authors: Akihiro Takeshita, Kaori Shinjo, Nozomi Yamakage, Takaaki Ono, Isao Hirano, Kenji Okinaka, Hirotaka Matsui, Satoki Nakamura, Kazuyuki Shigeno, Masato Maekawa, Kazunori Ohnishi, Ryuzo Ohno
Journal: Blood (2007)