tbuckley/cabot-search huggingface dataset:
Phase II trial of neoadjuvant/adjuvant imatinib mesylate (IM) for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumor (GIST): Long-term follow-up results of RTOG 0132.
Authors: D. Wang, Q. Zhang, C. D. Blanke, G. D. Demetri, M. C. Heinrich, J. C. Watson, J. P. Hoffman, S. H. Okuno, J. M. Kane, M. vonMehren, B. L. Eisenberg
Journal: Journal of Clinical Oncology (2011)

10057 Background: Imatinib mesylate (IM), which inhibits the KIT and PDGFR tyrosine kinases, has known activity against GIST. We previously reported early results of the first reported multi-institutional prospective trial (RTOG 0132) using neoadjuvant imatinib mesylate (IM) either in primary resectable GIST or as a planned preoperative cytoreduction agent for metastatic GIST (Eisenberg et al., JSO 2009). Methods: Patients with primary GIST (≥5cm, Group A) or operable metastatic/recurrent GIST (≥2 cm, Group B) received neoadjuvant IM (600 mg/day) for approximately two months and maintenance IM after surgery for 2 years. We have now updated the clinical outcomes including progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) at a median follow-up of 5.1 years and correlate these endpoints with duration of IM therapy. Results: Sixty-three patients were originally entered (53 analyzable), 31 patients in Group A and 22 in Group B. Estimated 5-year PFS and DSS were 57% A, 30% B; and 77% A, 77% B, respectively. Estimated 5-year OS was 77% for A, and 68% for B. Median time to progression has not been yet reached for Group A and is 4.4 years for Group B. In Cohort A, 7/11 patients progressed > 2 years from registration; 6/7 progressing patients had stopped IM prior to progression. In Cohort B, 10/13 patients progressed> 2 years from registration; 6/10 progressing patients had stopped IM prior to progression. The rate of treatment-related grade 4/5 toxicities was 23% (12/53). There was no increase in long term surgical complications using neoadjuvant and extended IM therapy. Conclusions: This long-term analysis of RTOG 0132 suggests a high percentage of patients progressed after discontinuation of 2-year maintenance IM therapy following surgical resection. Consideration should be given to studying longer treatment durations in high-risk GIST patients.
BCR-ABL–specific T-cell therapy in Ph+ ALL patients on tyrosine-kinase inhibitors
Authors: Patrizia Comoli, Sabrina Basso, Giovanni Riva, Patrizia Barozzi, Ilaria Guido, Antonella Gurrado, Giuseppe Quartuccio, Laura Rubert, Ivana Lagreca, Daniela Vallerini, Fabio Forghieri, Monica Morselli, Paola Bresciani, Angela Cuoghi, Ambra Paolini, Elisabetta Colaci, Roberto Marasca, Antonio Cuneo, Lorenzo Iughetti, Tommaso Trenti, Franco Narni, Robin Foà, Marco Zecca, Mario Luppi, Leonardo Potenza
Journal: Blood (2016)
Preliminary result of a multicenter phase II study of chemoradiotherapy with docetaxel for elderly patients with stage II/III esophageal carcinoma.
Authors: Jun Hashimoto, Namiko Kotani, Nobukazu Hokamura, Yoshinori Ito, Chikatoshi Katada, Hiromichi Ishiyama, Yoshio Tamaki, Takayuki Nakamura, Ken Kato
Journal: Journal of Clinical Oncology (2012)

122 Background: Definitive chemoradiotherapy (CRT) with 5-fluorouracil plus cisplatin (CDDP) is one of the most common treatment modalities for esophageal carcinoma (EC). However, there are limited data on CRT in elderly patients, and it is difficult for elderly patients to receive chemotherapy with CDDP due to poor organ function. The aim of this prospective study was to clarify the efficacy and safety of definitive CRT with docetaxel in elderly patients. Methods: Eligibility criteria included clinical stage II/III (UICC 6th, non-T4) EC, PS 0-1, age over 70 years, and no desire for surgical treatment. A total of 40 patients were planned for enrollment. Chemotherapy consisted of 6 cycles of a 1-h infusion of docetaxel (10 mg/m 2 ) repeated weekly. Radiation was concurrently administered to a dose of 60 Gy in 30 fractions. At this time, we evaluate the preliminary data of efficacy and safety of definitive CRT with docetaxel in elderly patients. Results: A total of 16 patients were enrolled between July 2008 and January 2011, at which point, the trial was closed due to poor accrual. The median age was 77 years (range, 73-81); male/female: 14/2; PS 0/1: 4/12; cStage IIA/IIB/III/IV: 3/4/8/1. Fourteen patients (88%) completed the treatment protocol, 1 patient (6%) could not complete the treatment because of severe toxicities, and 1 (6%) refused to continue the treatment. The complete response (CR) rate was 19% (3/16). In this preliminary analysis, the median follow-up time was 17 months. The 1-year survival rate was 87.5%. The most common grade 3 or 4 toxicities were esophagitis (31%), anorexia (13%), leukopenia (6%), neutropenia (6%), thrombocytopenia (6%), mucositis (6%), and infection (6%). No treatment-related deaths were observed. Grade 3 or 4 esophagitis, pleural effusion, pericardial effusion, and pneumonitis developed as late adverse events in 13%, 13%, 6%, and 6% of patients, respectively. Conclusions: This regimen is considered as feasible on hematological toxicities, however slightly toxic on non-hematological toxicities with modest activity. Lower rate of CR seemed to be due to severe esophagitis. Further follow-up is needed to estimate the efficacy of this treatment.
Lenalidomide Plus High-Dose Dexamethasone Provides Improved Overall Survival Compared to High-Dose Dexamethasone Alone for Relapsed or Refractory Multiple Myeloma (MM): Results of 2 Phase III Studies (MM-009, MM-010) and Subgroup Analysis of Patients with Impaired Renal Function.
Authors: Donna Weber, Michael Wang, Christine Chen, Andrew Belch, Edward A. Stadtmauer, Ruben Niesvisky, Zhinuan Yu, Marta Olesnyckyj, Jerome Zeldis, Robert D. Knight, Meletios Dimopoulos
Journal: Blood (2006)
Frequency and Clonality of BCR-ABL Compound Mutations in Chronic Myeloid Leukemia,
Authors: Jamshid Khorashad, Todd W. Kelley, Philippe Szankasi, Lauren T. Adrian, Christopher A. Eide, Matthew S. Zabriskie, Thoralf Lange, Ira L Kraft, Anna M Eiring, Thomas O'Hare, Michael W. Deininger
Journal: Blood (2011)
Inotuzumab Ozogamicin (CMC-544) In Patients with Indolent B-Cell NHL That Is Refractory to Rituximab Alone, Rituximab and Chemotherapy, or Radioimmunotherapy: Preliminary Safety and Efficacy From a Phase 2 Trial
Authors: Andre Goy, Joseph Leach, W. Christopher Ehmann, Kiyoshi Ando, Kiyohiko Hatake, Kensei Tobinai, Tatyana Feldman, Steven Hua, Angela DG Volkert, Erik R. Vandendries, Michinori Ogura
Journal: Blood (2010)
Benefit from CMF with or without anthracyclines in relation to biologic profiles in early breast cancer.
Authors: A. Rocca, A. Paradiso, P. Sismondi, E. Scarpi, A. Mangia, L. Medri, S. Bravaccini, D. Casadei Giunchi, D. Amadori, R. Silvestrini
Journal: Journal of Clinical Oncology (2011)

1031 Background: Anthracycline-containing regimens are considered superior to cyclophosphamide, methotrexate, and fluorouracil (CMF) as adjuvant therapy for early breast cancer, but predictors of anthracycline-derived benefit are lacking. We compared CMF and epirubicin (E) in different sequences with CMF alone in a phase III trial on rapidly proliferating breast cancer (RPBC), observing no differences in disease-free (DFS) or overall survival (OS). We performed a post hoc analysis on efficacy in relation to tumor biologic profiles. Methods: Patients (pts) with N−, T > 1 cm or ≤ 3 N+and any T RPBC, defined by thymidine labeling index or grade or S-phase or Ki67 (≥20), were randomized to receive E (100 mg/m2 i.v. q 21 d, 4 cycles) followed by CMF (600, 40, 600 mg/m2 i.v. d 1 and 8 q 28, 4 cycles) (arm A, 440 pts) or CMF followed by E (arm B, 438 patients) or CMF for 6 cycles (arm C, 188 pts, closed after the EBCTCG 2000 meta-analysis). Biological features were fully assessable in 755 pts (arm A/B/C: 303/309/143) and included estrogen (ER) and progesterone (PgR) receptors (cut off ≥10%), Ki-67 (very high: ≥40%) and HER2 (positive: 3+). DFS and OS were estimated with Kaplan-Meier curves and compared by log rank test and Cox models. Results: Among pts with triple negative RPBC, CMF yielded significantly worse 5-year DFS and OS rates compared with CMF and E sequences (Table). A very high Ki−67 (>40%) predicted a significantly worse 5-year DFS (59% vs 83%, p=.041) in pts treated with CMF, especially within the triple negative subset (38% vs 90%, p=.044), but not in the other treatment group. The interaction between treatment and tumor type (triple negative vs HER2-positive) was significant (p=0.001 for DFS, p=0.01 for OS). Conclusions: In pts with triple negative RPBC, CMF appears to be inferior to E and CMF combinations. A very high Ki-67 (≥40%) seems to identify pts among those with triple-negative phenotype who benefit from E. (%) 5-year DFS (95% CI) (%) 5-year OS (95% CI) No. pts CMF No. pts CMF→E →CMF p CMF CMF→E →CMF p Triple negative 31 59 (41-77) 128 85 (79-92) 0.002 73 (57-89) 91 (86-96) 0.002 ER- PgR- HER2+ 18 83 (65-100) 68 71 (60-82) 0.157 94 (84-100) 83 (74-92) 0.390 ER+ and/or PgR+, any HER2 94 82 (74-90) 416 85 (81-89) 0.133 93 (88-99) 95 (93-97) 0.435
Antitumor effects of combining doxorubicin hydrochloride with recombinant human endostatin in an osteosarcoma model.
Authors: H. Xu, X. Niu, Q. Zhang, L. Hao, Y. Ding, W. Liu, Z. Huang, L. Yao
Journal: Journal of Clinical Oncology (2011)

e20518 Background: During last 15 years, chemotherapy-based therapeutic regimens for the treatment of osteosarcoma have not demonstrated survival improvement. Novel approaches including targeted therapy and antiangiogenic therapy might give a new hope for the treatment of osteosarcoma as one of most deadly malignant diseases. Methods: Nude mice bearing established OS-732 human osteosarcoma received varying doses of recombinant human endostatin (rhEndostatin) alone and in combination with doxorubicin hydrochloride. Mice weight measurement was taken every 3 days. Tumor weight, microvessel density (MVD) and apoptotic index (AI) of the tumor were examined after mice were executed. Results: Low-dose rhEndostatin (2.5mg/kg) and doxorubicin hydrochloride alone (5mg/kg) showed inhibition of tumor growth by 25.3% and 29.1%, respectively. A combination of low-dose rhEndostatin and doxorubicin hydrochloride showed better antitumor activity with about 42.9%, suggesting a less than additive effect. High-dose rhEndostatin (10mg/kg) alone showed inhibition of tumor growth by 34.1%. However, a combination of high-dose rhEndostatin and doxorubicin hydrochloride showed a synergistic antitumor effect with tumor growth inhibition by approximately 64.8%. Conclusions: The combination of doxorubicin hydrochloride and rhEndostatin has synergetic activity, superior to any single agents. Our findings provide new guidelines for designing future clinical trials and for practice of these currently clinical available drugs (endostatin approved for clinical use in China) for the treatment of osteosarcoma.
Should Immunosuppressive Therapy (IST) Be Used More Often In Lower Risk MDS?
Authors: Sophie Cereja, Sabine Brechignac, Lionel Ades, Thorsten Braun, Simone Boehrer, Zehaira Hebibi, Rosa Sapena, Odile Beyne-Rauzy, Norbert Vey, Herve Dombret, Dominique Bordessoule, Francois Dreyfus, Pierre Fenaux, Claude Gardin
Journal: Blood (2010)
Breast cancer subtypes and outcome after local and regional relapse.
Authors: E. Montagna, V. Bagnardi, N. Rotmensz, G. Viale, G. Renne, G. Cancello, A. Balduzzi, E. Scarano, D. Pastrello, P. Veronesi, A. Luini, S. Zurrida, S. Monti, M. G. Mastropasqua, L. Bottiglieri, A. Goldhirsch, M. Colleoni
Journal: Journal of Clinical Oncology (2011)

1076 Background: Locoregional recurrences (LRR) may occur in up to one third of patients after primary therapy despite careful local treatment and systemic adjuvant therapies and or radiotherapy A better description of relapse patterns may improve patient outcome by permitting a better understanding of patients subgroup-specific risk, which could lead to targeted therapeutic approaches. Methods: We collected information on all consecutive breast cancer patients operated at the European Institute of Oncology between 1994 and 2005. The tumor characteristics and subsequent outcome of patients who experienced local and regional recurrence was analyzed. Results: 279 patients with LRR were identified, 197 and 82 patients with local and regional recurrence respectively. The overall discordance rate between primary cancer and LRR was 9% for ER expression, 22% for PgR and 4% for HER2. Among patients with local recurrence the risk of subsequent relapse and death was significantly higher in those with early (< 2 years) compared to delayed local recurrence [HR for PFS 3.34 (1.86-6.00); HR for OS 2.29 (1.47-3.55)] Patients with triple negative breast cancer at LRR experienced an higher risk of subsequent relapse [HR 2.87 (1.67-4.91)] and death [HR 2.00 (1.25-3.19)]. Conclusions: LRR correlates with a high risk of subsequent events and death in particular in patients with triple negative subtype. Treatments to prevent subsequent events may be most efficiently studied in populations with triple negative breast cancer.
Ibrutinib for patients with rituximab-refractory Waldenström's macroglobulinaemia (iNNOVATE): an open-label substudy of an international, multicentre, phase 3 trial
Authors: Meletios A Dimopoulos, Judith Trotman, Alessandra Tedeschi, Jeffrey V Matous, David Macdonald, Constantine Tam, Olivier Tournilhac, Shuo Ma, Albert Oriol, Leonard T Heffner, Chaim Shustik, Ramón García-Sanz, Robert F Cornell, Carlos Fernández de Larrea, Jorge J Castillo, Miquel Granell, Marie-Christine Kyrtsonis, Veronique Leblond, Argiris Symeonidis, Efstathios Kastritis, Priyanka Singh, Jianling Li, Thorsten Graef, Elizabeth Bilotti, Steven Treon, Christian Buske
Journal: The Lancet Oncology (2016)
Autologous-Collected Donor-Derived CD19-Directed Chimeric Antigen Receptor (CD19-CAR) T Cells Induce a Complete Remission in Chemotherapy-Refractory Childhood Acute Lymphocytic Leukemia (ALL) Relapsing After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT).
Authors: Daniel W. Lee, Maryalice Stetler-Stevenson, Marianna Sabatino, Barbara Tumaini, Kelly Richards, Cindy Delbrook, James N Kochenderfer, Steven A. Rosenberg, David Stroncek, Crystal L Mackall, Alan S Wayne
Journal: Blood (2012)
Comparison of T-FEC therapy for HER2-negative breast cancer with TC6 cycle therapy
Authors: H. Abe, Y. Kawai, T. Mori, H. Cho, Y. Kubota, T. Umeda, Y. Kurumi, T. Tani
Journal: Journal of Clinical Oncology (2011)

e11513 Background: TC4 cycle therapy was more useful than AC4 cycle therapy. In this study, we compared the treatment completion rate and safety of a regimen involving anthracycline, T-FEC (docetaxel followed by FEC) therapy, with those of TC6 cycle therapy in patients with HER2-negative breast cancer in whom there may be no topoisomerase IIa amplification. Methods: We administered T-FEC q3w or TC q3w to HER2-negative breast cancer patients with axillary lymph node metastasis, or high-risk breast cancer patients without metastasis. As a primary endpoint, the treatment completion rate was evaluated. As secondary endpoints, the safety such as short- and long-term toxicity including cardiac toxicity, as well as the administration state, were assessed. Results: The T-FEC group consisted of 21 patients. The TC6 group consisted of 22 patients. There were no significant differences in the patient background between the two groups. In the T-FEC group, the treatment completion rate and relative dose intensity were 95.2 and 98.90%, respectively. In the TC6 group, the values were 86.4 and 93.2%, respectively. Concerning hemotoxicity, Grade 3 or higher adverse reactions included neutropenia (T-FEC group: 33%, TC6 group: 41%) and febrile neutropenia (TC6 group: 14%). As non-hemotoxicity adverse reactions, general malaise, nausea/vomiting, anorexia, and stomatitis were noted in 52, 38, 48, and 33% of the patients in the T-FEC group, respectively. The incidence of nausea/vomiting was significantly higher in this group. In the TC6 group, general malaise, nausea/vomiting, anorexia, and stomatitis were observed in 46, 9, 37, and 18% of the patients, respectively. In addition, exanthema and peripheral neuropathy were noted in 23 and 50%, respectively. These percentages were significantly higher. Conclusions: With respect to adverse reactions, exanthema and peripheral neuropathy were characteristic of TC6 cycle therapy, and T-FEC therapy frequently caused nausea/vomiting. These results suggest that TC6 cycle therapy is tolerable, and that this regimen can also be performed at outpatient clinics. However, in the TC6 group, the treatment completion rate was slightly lower than in the T-FEC group; appropriate supportive therapy may be necessary.
How does neoadjuvant bicalutamide 150 mg monotherapy compare to lutenising hormone-releasing hormone agonist (LHRHa) therapy in localized prostate cancer treated with radical radiotherapy? A case-matched comparison of PSA kinetics and biochemical outcome.
Authors: U. McGivern, D. M. Mitchell, J. O'Hare, G. Corey, J. M. O'Sullivan
Journal: Journal of Clinical Oncology (2011)

146 Background: In patients treated with neoadjuvant lutenising hormone-releasing hormone agonist (LHRHa) therapy prior to radical prostate radiotherapy the PSA nadir in the first week of radiotherapy has been correlated with subsequent biochemical failure free survival (BFFS). Bicalutamide monotherapy (BC) is increasingly being used as a neoadjuvant therapy in place of LHRHa. We wished to compare the initial PSA response to neoadjuvant BC or LHRHa in this setting as well as examining subsequent biochemical failure rates. Methods: We retrospectively reviewed the case notes of consecutive men with prostate cancer treated with BC monotherapy prior to radical prostate radiotherapy from April 2004 to December 2008 and case-matched them to men treated with neoadjuvant LHRHa. PSA levels and kinetics prior to radiotherapy and subsequent BFFS were analysed. Results: Eighty nine men treated with BC with a median follow-up of 42 months were case matched to 89 men treated with LHRHa. There were no significant differences in age, initial PSA, Gleason, or T stage. The median nadir PSA on day 1 of radiotherapy was 2.2ng/mL (0.1-11.2) for BC patients and 0.9ng/mL (0.1-11.2) for LHRHa patients (p=0.0007). There were no significant differences in PSA velocity or doubling time during the neoadjuvant period. A PSA of &lt;1.0ng/mL on day 1 of radiotherapy was seen in 29 (32%) and 47 (52%) of BC and LHRHa patients respectively. Biochemical failure was seen in 10 (11.2%) and 2 (2.2%) of BC and LHRHa patients respectively. PSA kinetics did not predict for subsequent BFFS at this duration of FU for men receiving neoadjuvant BC. Conclusions: In this case-matched study, neoadjuvant BC therapy does not provide the same level of pre-radiotherapy PSA suppression when compared to neoadjuvant LHRHa. Higher biochemical failure rates are seen in patients treated with BC than LHRHa however this may be a result of prolonged castration. No significant financial relationships to disclose.
Survival outcomes of neoadjuvant hormone therapy plus external-beam radiotherapy with relatively early initiation of salvage hormone therapy to patients with T3-4N0M0 prostate cancer.
Authors: T. Mizowaki, Y. Norihisa, M. Ogura, T. Kamba, T. Inoue, Y. Shimizu, O. Ogawa, M. Hiraoka
Journal: Journal of Clinical Oncology (2011)

95 Background: Survival benefits of adding long-term adjuvant hormonal therapy (A-HT) on external beam radiation therapy (EBRT) had reported in patients with locally advanced prostate cancer. However, adverse effects of long-term hormonal therapy are also not negligible. If early initiation of salvage hormonal therapy (S-HT) to patents developed PSA failure after EBRT can realize comparable survival as to giving A-HT across the board, patients who maintain biochemical failure-free status after EBRT will receive hormonal-free benefit. We analyzed outcomes of EBRT combine with neoadjuvant hormonal therapy (NA-HT) to patients with T3-4N0M0 prostate cancer. Methods: Between April 1998 and Mar 2006, consecutive 173 Japanese patients with T3-4N0M0 adenocarcinoma of the prostate were definitively treated by 3D-CRT / IMRT. The median age was 72 years old (range 48-80). Pre-treatment PSA values ranged between 3.7 and 430 ng/ml (mean: 45.3). T-stage was distributed as follows: T3a: 122, T3b: 50 and T4: 1 case. NA-HT (3–17 months, median: 5 months) was given to all cases. Mean delivered dose was 74 Gy in 2 Gy per fraction to the prostate and seminal vesicles (range: 60-78). A-HT was not given to any patients and PSA values were monitored with one to 6 months interval after the treatment. S-HT was essentially started when PSA value exceeded 4 ng/ml. Results: Median follow-up period was 74 months (range: 8–152). So far, S-HT was initiated to 58 patients, and PSA values at the initiation of S-HT ranged 0.1 to 32.2 with a median value of 6.0 ng/ml. Biochemical relapse-free survival by the Phoenix definition and salvage hormonal therapy-free survival rates at 8 years were 60% (95% CI = 51-68) and 63% (95% CI = 56-71), respectively. Prostate cancer-specific and overall survival rates were 94% (95% CI = 89-99) and 85% (95% CI = 78-92), respectively. Conclusions: Survival rates of this cohort of patients treated by EBRT combined with NA-HT were excellent despite no A-HT was given, and more than two thirds of patients maintained hormone-free status at 8 years. This approach may be an alternative to giving long-term A-HT. No significant financial relationships to disclose.
Observational Prospective Registry for the Assessment of the Clinical Impact of Starting Anti-Myeloma Treatment at Biological Relapse
Authors: Adrian Alegre, Merche Gironella, Juan Miguel Bergua, Esther Gonzalez, Fernando Escalante, Alfon Soler, Antonia Sampol, Ana Pilar Gonzalez, Valentin Cabañas, Juan Jose Lahuerta, Aurelio Lopez, Ana Dios, Abelardo Bárez, Antonio Ruiz, David Vilanova, Joaquín Díaz-Mediavilla
Journal: Blood (2014)
Ten doctors are charged in Texas hospital referral bribery scheme
Authors: Owen Dyer
Journal: BMJ (2016)

Ten doctors, including some of the Dallas area’s most prominent physicians, face federal fraud and other charges over a “massive, multifaceted” network of kickbacks and bribes through which the wealthy consultants and surgeons of an upmarket hospital chain bought referrals of patients with high value insurance.

The 10 doctors are among 21 people charged in a scheme allegedly run by the now defunct Forest Park Medical Centers, a chain of luxury hospitals that sprang up and flourished briefly in prosperous areas across Texas and in Kansas, backed largely by physician investors.

The group’s founders and investors enriched themselves by refusing to join insurer physician networks, then concentrated on patients with generous insurance plans, including military and government employee plans, that allowed “out of network” billing, the …
Immune Dysfunction in Patients with MDS Is Partially Corrected in EPO-Treated Patients: Differences According to WHO Classification
Authors: Howard S Oster, Naamit Deshet-Unger, Drorit Neumann, Moshe Mittelman, Nir Maaravi, Sara Prutchi-Sagiv, Golishevski Nataliya
Journal: Blood (2016)
Suppression of Erythroid-Specific 5-Aminolevulinate Synthase Using Short-Interfering RNA Alters Iron Metabolism and Inhibits Terminal Differentiation of Human Erythroleukemia Cells.
Authors: Kazumichi Furuyama, Kiriko Kaneko, Zhang Yongzhao, Patrick D. Vargas V., Shigeru Sassa, Shigeki Shibahara
Journal: Blood (2004)