tbuckley/cabot-search huggingface dataset:
Preliminary safety results of regorafenib (REG) as a single agent for first-line treatment of frail and/or unfit for polychemotherapy patients (pts) with metastatic colorectal cancer (mCRC): A phase II study of the Spanish Cooperative Group for Digestive Tumor Therapy (TTD).
Authors: Alfredo Carrato, Bartolomeu Massuti Sureda, Manuel Benavides, Carmen Guillén Ponce, Esther Falco, Pilar Garcia Alfonso, Margarita Reboredo, Maria Teresa Cano, Javier Gallego, Jose Maria Vieitez de Prado, Laura Layos, Antonia Salud, Vicente Alonso, Emma Dotor, Ana Yuste, Silvia Gil, Reyes Ferreiro Monteagudo, Teresa Fernandez Rodriguez, Enrique Grande, Enrique Aranda
Journal: Journal of Clinical Oncology (2015)

e14524 Background: Around 15-20% of pts diagnosed of mCRC do not qualify to receive polychemotherapy as first-line therapy, due to age and/or comorbidities, and their optimal treatment strategy has not been defined. REG is an oral multikinase inhibitor currently used as standard of care for fit pts with pretreated mCRC. This trial will assess the efficacy and safety of REG as a single agent in the first-line setting of this group of pts. Primary endpoint is progression-free survival rate at 6 months. Methods: Phase II, single-arm, open-label study in mCRC pts who were frail and/or unfit to receive polychemotherapy. Main inclusion criteria: pts > 18 years, ECOG PS ≤ 2, adequate organ function, and at least one of the following criteria: dependence in activities of daily living, presence of three or more comorbidities or geriatric syndromes. Pts received regorafenib 160 mg PO, 3 weeks on/1 week off in a 4-week cycle. Results: Forty-four pts have been analyzed. Median age was 80 years, 36.4% had ECOG 2, 57% were dependent, 40.9% had geriatric syndromes and 57% ≥ 3 comorbidities: hypertension (47.7%), diabetes mellitus (38.6%) and chronic cardiovascular diseases (36.4%); 71.8% had ≥ 2-affected organs and 38.6% did not undergo surgery of their primary tumor. Treatment: 131 cycles were administered (median 2, range 1-9). Median dose intensity was 75%. 46% required dose reductions and 22% dose delays. Nine pts discontinued treatment due to toxicity. Two pts (4.5%) had grade 4 toxicity: hyperuricemia and lipase increase, and two pts grade 5 toxicity: one sudden death and one rectorrhagia. Most frequent grade 3 toxicities were fatigue (34.1%), hypertension (29.3%), hypophosphatemia (9.8%) and increased AST (7.3%); 12.2% had grade 2-3 skin and subcutaneous toxicity. Conclusions: In this particular population of frail or unfit pts with various comorbidities, first-line regorafenib at standard starting dose led to a high rate of adverse events with frequent dose reductions and/or delays. The trial has not enough follow-up for efficacy results reports. Clinical trial information: NCT01875380.
Patient-provider communication during post-treatment breast cancer care: Findings from a pilot project.
Authors: Neetu Chawla, Michael Sanchez, Jayson Harpster, Leslie Manace Brenman, Raymond Liu
Journal: Journal of Clinical Oncology (2017)

91 Background: Patient-provider communication is essential to delivering high quality cancer care, including post-treatment when survivors have many complex care needs. In this study, we used data collected for quality improvement from a small, feasibility sample to examine patient perceptions of provider communication and inform the development of a new Oncology Survivorship Clinic model. Methods: As part of a pilot project conducted at Kaiser Permanente Northern California (KPNC), we surveyed 51 breast cancer patients post-treatment. The survey included a communication measure from the 2011 Medical Expenditure Panel Survey (MEPS) Experiences with Cancer survey evaluating provider discussions of: surveillance for recurrence; late or long-term treatment effects; healthy lifestyle behaviors; and emotional or social needs. We also examined reports of the six core functions of patient-centered communication (i.e. managing uncertainty, responding to emotions, making decisions, fostering healing relationships, enabling self-management, and exchanging information) using a measure from the Health Information Trends Survey (HINTS) survey. Part of the purpose was to evaluate acceptability of a new Oncology Survivorship Clinic utilizing non-physician providers. Results: The sample included 51 breast cancer patients surveyed in 2016 within six months of treatment completion. Overall, sizable proportions received detailed communication about surveillance (65%), treatment side effects (46%), emotional needs (41%), and healthy lifestyles (71%) and the majority received patient-centered communication (range: 60-73% based on core function). Particular gaps were noted related to provider communication about treatment side effects (54%), emotional/social needs (59%), managing uncertainty (35%), and responding to emotions (40%). Conclusions: Our very preliminary findings suggest that the majority of women had positive communication experiences, including with non-physician providers. However, clear communications gaps existed underscoring future avenues for research and care delivery interventions to address the comprehensive needs of breast cancer patients.
Aberrant tumor metabolism to enable glucocorticoid receptor takeover in enzalutamide-resistant prostate cancer.
Authors: Nima Sharifi, Jianneng Li, Mohammad Alyamani, Ao Zhang, Kai-Hsiung Chang, Mike Berk, Zhenfei Li, Ziqi Zhu, Marianne Petro, Mary-Ellen Taplin, Jorge A. Garcia, Kevin Dale Courtney, Eric A. Klein
Journal: Journal of Clinical Oncology (2017)

157 Background: Prostate cancer is driven by androgen stimulation of the androgen receptor (AR). The next-generation AR antagonist, enzalutamide, prolongs progression-free and overall survival, but resistance and lethal disease eventually prevail. Emerging data suggest that the glucocorticoid receptor (GR) is upregulated in this context, stimulating expression of approximately 50% of genes normally stimulated by AR, thereby permitting continued growth despite AR blockade. However, countering this mechanism by administration of GR antagonists is problematic because GR is essential for life. Methods: We assessed the effects of enzalutamide on metabolism of cortisol to cortisone in the LAPC4 and VCaP models of prostate cancer using [ 3 H]-cortisol and high performance liquid chromatography. Expression of 11β-hydroxysteroid dehydrogenase-2, encoding the enzyme 11βHSD2, which converts cortisol to cortisone, was assessed by immunoblot, in models of prostate cancer, tissues from patients treated with enzalutamide and prostate tissues treated exogenously with enzalutamide. The effect of shRNA knockdown of the AMFR ubiquitin E3-ligase on 11βHSD2 protein expression and enzyme activity was assessed. Finally, the potential therapeutic effects of 11βHSD2 re-expression on enzalutamide resistance was assessed in xenograft models. Results: Enzalutamide impedes inactivation of cortisol to cortisone, thereby sustaining tumor cortisol concentrations, permitting GR stimulation and enzalutamide resistance. Impeded cortisol inactivation by enzalutamide occurs by way of 11β-HSD2 expression loss in models of prostate cancer, prostate tissues from enzalutamide-treated patients and fresh prostatic tissues treated exogenously with enzalutamide. AMFR mediates loss of 11β-HSD2, which otherwise inactivates cortisol. Remarkably, reinstatement of 11β-HSD2 expression, or AMFR loss, reverses enzalutamide resistance in mouse xenograft tumors. Conclusions: Together, these findings reveal a surprising metabolic mechanism of enzalutamide resistance that may be targeted with a strategy that circumvents a requirement for systemic GR ablation.
Actual 5-year survivors following resection of hilar cholangiocarcinoma.
Authors: Thuy Tran, Cecilia Grace Ethun, Timothy M. Pawlik, Stefan Buettner, Kamran Idrees, Chelsea A Isom, Ryan C. Fields, Bradley Krasnick, Sharon M. Weber, Ahmed Salem, Robert C. G. Martin, Charles Raben Scoggins, Perry Shen, Harveshp Mogal, Carl Richard Schmidt, Eliza W Beal, Ioannis Hatzaras, Rivfka Shenoy, Shishir Kumar Maithel, George A. Poultsides
Journal: Journal of Clinical Oncology (2017)

352 Background: Although several studies have reported on actuarial survival outcomes following resection of hilar cholangiocarcinoma, the characteristics of patients who actually reached the 5-year milestone have not been adequately described. Methods: Patients who underwent resection for hilar cholangiocarcinoma from 2000-2015 in 10 US academic institutions participating in the Extrahepatic Biliary Malignancy Consortium were analyzed. Patients alive at last encounter with less than 5 years of follow-up were excluded. The clinicopathologic characteristics, perioperative, and long-term outcomes of actual 5-yr survivors and of patients who died within 5 years were compared. Results: Of 328 patients explored, 257 (78%) underwent curative resection and had an actuarial 5-year survival of 17%. After excluding 63 survivors with &lt; 5 years follow-up, 194 patients were further classified as 5-year survivors (n = 23, 12%) and non-5-yr survivors. None of the 5-yr survivors had preoperative systemic biliary sepsis, portal vein embolization, T3 tumors with unilateral portal vein or hepatic artery invasion, or T4 tumors necessitating main portal vein or hepatic artery resection. However, actual 5-year survival was still achieved in the setting of bile duct resection only, R1 margins, poor differentiation, lymphovascular or perineural invasion, nodal metastasis, intraoperative blood transfusion, and serious postoperative complications. Five-year survival did not equal cure, as five 5-year survivors experienced disease recurrence, 2 before and 3 after the 5-year mark. There were ten actual 7-year survivors and four actual 10-year survivors. Conclusions: Although nodal metastasis, poor differentiation, and R1 margins are established predictors of poor outcome for hilar cholangiocarcinoma, the mere presence of these factors does not preclude patients from achieving a 5-year survival. In contrast, preoperative biliary sepsis, T3 or T4 stage, and the necessity for vascular resection and reconstruction appear to be prohibitive in reaching the 5-year milestone. This information can be utilized in the perioperative counseling of patients with this challenging malignancy.
FOLFIRI plus 5 mg/kg of bevacizumab versus 10 mg/kg as second-line therapy in patients with metastatic colorectal cancer who have failed first-line bevacizumab plus oxaliplatin-based therapy: A randomized phase III study (EAGLE Study).
Authors: Masato Nakamura, Hideyuki Mishima, Shigeyoshi Iwamoto, Takao Takahashi, Hiroshi Tamagawa, Yoshinori Munemoto, Taishi Hata, Tadamichi Denda, Yoshitaka Morita, Michio Inukai, Akihiko Murata, Katsuyuki Kunieda, Naoki Nagata, Yoshitaka Kurachi, Takashi Oshiro, Kenji Ina, Yuji Miyamoto, Tatsu Shimoyama, Koji Oba, Junichi Sakamoto
Journal: Journal of Clinical Oncology (2012)

TPS3642 Background: There has been much controversy about continuation of bevacizumab (BV) with a second-line regimen after progression on a BV-containing first-line regimen. Recently, it was announced that a phase III study (AIO 0504 / ML 18147) met its primary endpoint of overall survival. It means BV-based regimen (5 mg/kg) extends survival when continued beyond initial treatment in patients with metastatic colorectal cancer(mCRC). The verified data from a randomized phase III study (E3200) indicates that BV at 10 mg/kg in the second-line setting followed by BV-naive treatment extends survival. The dose of BV 5 mg/kg could be lower than the recommended dose in the second-line CRC treatment. Thus we planned this second line phase III study (EAGLE study) to evaluate the appropriate dose of BV (5 or 10 mg/kg) with FOLFIRI in patients with mCRC who have failed BV plus oxaliplatin-based first line regimen. Methods: EAGLE is a multicenter randomized phase III study of FOLFIRI plus BV 5 mg/kg versus 10 mg/kg in mCRC who have failed BV plus oxaliplatin-based first line regimen (UMIN000002557).The primary endpoint is PFS. The secondary endpoints are the toxicity, response rate, time to treatment failure, OS. Eligible patients were older than 20 years of age, had histologically proved CRC, ECOG performance status 0 or 1, adequate organ function, progression or difficult to continue after BV plus oxaliplatin-based first line regimen, more than four times administration of BV and oxaliplatin in the first-line. Patients were randomized 1:1 to FOLFIRI with BV 5mg/kg or 10 mg/kg.The planned sample size was 370 patients to detect 30% risk reduction (median PFS assumed to be 5.0 months in arm A, 7.0 months in arm B) with 90% power assuming a two-sided significance level of 0.05, an accrual time of 2.5 years and a follow-up time of 1 year. Between September 2009 to January 2012, 387 patients were enrolled at 100 sites in Japan. This phase III study will answer the question of the appropriate dose of BV after progression on a BV-containing first-line regimen.
TERAPIA DE ASPIRACIÓN COMO TRATAMIENTO DE LA OBESIDAD
Authors: R Turro Arau, JC Espinos Perez, J Turró Homedes, A Mata Bilbao
Journal: Endoscopy (2015)

Presentamos los resultados del tratamiento endoscópico de la obesidad con el sistema de aspiración AspireAssist® en pacientes con obesidad mórbida. El sistema AspireAssist consiste en la colocación vía endoscópica de un tubo de gastrostomía (A-Tube) que unido al uso de un equipo externo, permite realizar una aspiración controlada del contenido gástrico 20 minutos tras la ingesta, eliminando hasta un 30% del contenido calórico. Presentamos los resultados a los 6 y 12 meses del tratamiento.
Contents, Vol. 66, 1997
Authors: Scott B. Patten, Luanne M. Metz, James E. Aikens, Theresa A. Kiolbasa, Robert Sobel, Alvise Orlandini, Matteo Rocco Pastore, Andrea Fossati, Stefano Clerici, Alessandro Sergi, Annalisa Balini, Cesare Maffei, Antonio Secchi, Guido Pozza, Isao Fukunishi, Masaki Hattori, Douglas Berger, Isao Fukunishi, Mary Alice O'Dowd, Giovanni A. Fava, Ludwig Teusch, Hildegard Böhme, Markus Gastpar, Takashi Hosaka, Tomifusa Kuboki, Yoshihiro Ishikawa, Ernest H. Friedman
Journal: Psychotherapy and Psychosomatics (1997)
En bloc resection of pulmonary sulcus non-small cell lung cancer invading the spine: A systematic review and pooled analysis.
Authors: Stephane Collaud, Elie Fadel, Joachim Schirren, Hiroyasu Yokomise, Servet Bolukbas, Philippe Dartevelle, Shaf Keshavjee, Thomas K. Waddell, Marc de Perrot
Journal: Journal of Clinical Oncology (2013)

e18503 Background: Treatment of locally advanced NSCLC is debated. While survival for inoperable disease ranges between 3-17%, carefully selected patients can be cured when treated surgically in a multimodality concept. Here, we conducted a systematic literature review and pooled data analysis of patients after en bloc resection for pulmonary sulcus NSCLC invading the spine. Outcome and prognostic factors were described. Methods: The MEDLINE database was searched using the PubMed engine to retrieve all relevant articles related to en bloc resection for pulmonary sulcus NSCLC invading the spine. All articles’ corresponding authors were contacted to share their most updated anonymized patient’s data. Data were pooled and analyzed, focusing on outcome and prognostic factors. Results: Search strategy yielded a total of 134 articles. Out of these, only 6 were relevant and non-duplicative. Four out of 6 authors were able to share updated data for a total of 135 patients. All tumors were resected en bloc with the lung, chest wall and spine. Induction treatment was administered in 87 (64%) patients and consisted of chemotherapy (n=32), radiation (n=1) or concurrent chemoradiation (n=54). Spine resections included total (n=23), hemi- (n=94) and partial (n=18) vertebrectomies. Complete resection was achieved in 120 (89%) patients. Five patients died in the postoperative period (4%). Adjuvant treatment was administered in 70 (52%) patients and included chemotherapy (n=16), radiotherapy (n=22) or chemoradiation (n=32). Median follow-up was 26 months. Overall 3-, 5- and 10-year survivals were 57%, 43% and 27%, respectively. Results of the univariate analysis (Cox, Breslow tests) identified incomplete surgical resection (R0 vs R1/2, p&lt;0.001) as the only significant prognostic factors among the variables tested (age, histology, pN stage, type of induction/adjuvant treatment, type of lung resection). Conclusions: Multimodality therapy including en bloc resection for pulmonary sulcus NSCLC invading the spine provides excellent long-term survival. Complete surgical resection is the only determinant for survival. No difference was shown for patients treated with induction vs adjuvant therapy.
Longitudinal whole body MRI (wbMRI) in monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma.
Authors: Maximilian Merz, Barbara Wagner-Gund, Kai Neben, Anthony D. Ho, Hartmut Goldschmidt, Jens Hillengass
Journal: Journal of Clinical Oncology (2013)

8590 Background: The detection of bone marrow focal lesions (FLs) by MRI at the initial work up has prognostic significance in multiple myeloma (MM), smoldering MM as well as MGUS. Currently, there are no data available on the predictive relevance of new FLs or FLs increasing in size in longitudinally performed wbMRIs for the follow-up of sMM and MGUS. Methods: We retrospectively analyzed 87 patients (sMM n=65; MGUS n=22) that received at least 2 (up to 5) wbMRIs for follow-up. The date of progression into MM requiring systemic therapy was defined as event for the analysis of progression free survival (PFS). Radiological progressive disease (rPD) was defined as the appearance of novel FLs or increase in size of preexisting FLs. Kaplan-Meier plots of PFS for patients with rPD and patients without rPD were analyzed using the log-rank test for significant differences. Results: Median follow-up was 61 months (9.8-101) with a median time between follow-up wbMRIs of 15.8 months (1-73). Progression from sMM/MGUS into MM was found in 28 patients (sMM 40%; MGUS 9%). Using wbMRI, rPD was found in 21 patients (sMM 32%; MGUS 0%). Of all patients, 76% (n=16) with rPD and 16% (n= 9) without rPD progressed into MM during the observation period. Analysis of Kaplan Meyer plots for PFS revealed a highly significant shorter PFS for patients with rPD (32 months) compared to patients with radiological stable disease in wbMRI (PFS not reached; p&lt;0.0001). New appearance or progression of diffuse bone marrow infiltration was not associated with a shorter PFS (not reached; p&gt;0.05). Conclusions: In our study, the appearance of novel FLs or progression of preexisting FLs was highly predictive for progression from sMM into MM requiring systemic treatment. We conclude that wbMRI is effective for the longitudinal follow-up of patients with sMM and MGUS and identifies a group of patients at risk for progression into MM.
Phase I trial of chir-258 in multiple myeloma
Authors: S. Lonial, M. Alsina, K. C. Anderson, P. Richardson, K. Stewart, R. Fonseca, C. Heise, J. Fox, A. Allen, G. Michelson
Journal: Journal of Clinical Oncology (2006)

17502 Background: CHIR-258 is an orally active small molecule receptor tyrosine kinase (RTK) inhibitor which has potent activity against multiple RTKs involved in tumor growth and angiogenesis (IC50 ≤13 nM for FGFR, VEGFR, PDGFR, C-KIT, and FLT3). Approximately 15% of newly diagnosed MM patients harbor a t(4;14) translocation, which results in ectopic expression of FGFR3 and MMSET and is associated with poor treatment outcome [0]and reduced survival. CHIR-258 inhibits proliferation and induces apoptosis in FGFR3-expressing MM tumor xenografts as well as FGFR3-expressing primary MM cells (Trudel et al, Blood 2005). CHIR-258 was synergistic with dexamethasone (dex) in vitro. Methods: CHIR-258 was administered once daily in a dose-escalating phase 1 study to patients with relapsed/refractory MM. Drug tolerability and safety, pharmacokinetics (PK) and pharmacodynamics (PD) were assessed. Results: as of December 2005, 9 total pts have been treated (50, 100, and 200mg qd cohorts) [6M, 3F; median age: 58 (range: 44–68), median of 3 prior therapies(range:1–7)]. Prior tx: 9/9 pts-thalidomide; 8/9 -Velcade; 8/9-transplant; 8/9- had progressed through dex. 4 of 9 pts treated were FGFR3+ and 4 pts remain on study (3 are FGFR3+). No CR or PR have been observed; stable disease has been noted. CHIR-258 has been generally well tolerated, and most drug related AEs were CTC grade 1 or 2, including: headache, dysgeusia, fatigue and anorexia. No neuropathy. One DLT has been observed to date: neutropenia (200mg cohort). Five pts had dex added to CHIR-258 of which 3 are ongoing (all FGFR3+). FGFR3+ pts receiving dex and CHIR-258 have a greater decline in urine and serum paraproteins (pp) vs CHIR-258 alone. Plasma exposure and Cmax increased proportionally across the doses. Conclusions: CHIR-258 is a novel inhibitor of RTKs involved in MM growth and proliferation. FGFR3+ pts have a more marked reduction in pp than FGFR3- pts. CHIR-258 has generally been well tolerated and further accrual continues. [Table: see text]
Update on a phase II study of cyclophosphamide, etoposide and estramustine in patients with androgen independent prostate cancer
Authors: P. U. Moffett, M. A. Choudry, L. A. Ferguson, D. A. Williams, R. V. La Rocca, F. J. Hendler, D. A. Laber
Journal: Journal of Clinical Oncology (2006)

4647 Background: Oral therapy offers the tremendous advantage of independence and avoids all the catheter-related complications. Cyclophosphamide (C), etoposide (E) and estramustine (E) are active against androgen-independent prostate cancer (AIPC). The optimal dose and schedule of these agents have not been defined. Methods: Objectives are to evaluate the efficacy and safety of this triple drug regimen (CEE). Each treatment cycle consists of cyclophosphamide 50 mg/m 2 p.o., etoposide 50 mg/m 2 p.o. and estramustine 280 mg p.o. administered on days 1–14, every 28 days. Response was assessed by changes in size of measurable and non-measurable lesions (RECIST JNCI 92(3):205–216, 2000), and PSA levels (JCO 17(11):3461–7, 1999). Results: Twenty-nine subjects with AIPC were enrolled. 25 patients, who completed at least 2 cycles, are evaluable for toxicity and response. Median baseline characteristics: age 68 years (52–86); ECOG performance status 2 (0–3); PSA 148 ng/ml (26–2268); and 8 had prior chemotherapy. Total number of cycles administered: 98 with median of 3 cycles/patient. Response: PSA response: Out of 25 subjects, 7 (28%) had &gt;50% decrease and 5 (20%) had &gt;75% decrease, for an overall PSA response of 58%. Measurable disease: 13 patients had measurable lesions by RECIST criteria. One pt had a complete response (8%), seven had SD (54%) and there were 5 PD (38%). 44% of the subjects experienced an improvement in their ECOG performance status and 64% reported improvement in their level of pain. Toxicity: Grade 3–4: 36% neutropenia, 12% thrombocytopenia, 5% anemia. Four patients (27%) developed a thrombotic event. 3 with DVTs, two spontaneous and one after a 14-hours car trip. One subject with a strong history of cardiac complications had a myocardial infarction. Neutropenic fever requiring antibiotic use occurred in 2 patients. Conclusions: CEE is a well-tolerated, all oral, easy to administer and effective triple drug therapy for patients with metastatic androgen-independent prostate cancer. No significant financial relationships to disclose.