tbuckley/cabot-search huggingface dataset:
Pooled safety analysis of omacetaxine mepesuccinate in patients with chronic myeloid leukemia (CML) resistant to tyrosine-kinase inhibitors (TKIs).
Authors: Meir Wetzler, Hagop Kantarjian, Franck E. Nicolini, Jeffrey Howard Lipton, Luke Paul Akard, Michele Baccarani, Adam Craig, Peter D. Brown, Jorge E. Cortes
Journal: Journal of Clinical Oncology (2012)

6604 Background: Subcutaneous omacetaxine mepesuccinate (“omacetaxine”) is a reversible, transient inhibitor of protein elongation that does not depend on BCR-ABL signaling. It showed significant clinical activity in two phase 2, open-label, multicenter studies of patients with CML who were resistant/intolerant to prior TKI therapy. However, omacetaxine tolerability data across the 3 phases of CML are limited. Methods: Safety data were pooled from all patients in the 2 studies plus a small pilot study. Omacetaxine 1.25 mg/m 2 was given subcutaneously twice daily: ≤14 successive days per 28-day cycle for induction, ≤7 days/cycle as maintenance. Days of dosing could be adjusted and recombinant growth factors given, as clinically indicated. Results: Of 207 pooled patients (median age, 57 years), 108 were in chronic (CP), 55 in accelerated (AP), and 44 in blast phase (BP). Median treatment was 4 cycles (range, 1–41). On study, 80% of patients had ≥1 hematologic adverse event (AE), 60% had a serious AE (SAE), 30% had a hematologic SAE, 34% had an SAE that resulted in hospitalization, and 15% discontinued treatment due to an SAE (most commonly disease progression). There were 49 (24%) deaths (15 CP, 11 AP, and 23 BP). Of the 8 that were treatment related (5 CP, 2 AP, 1 BP), the most common cause was sepsis (3 patients). The most common AEs were thrombocytopenia (60%), anemia (51%), diarrhea (40%), neutropenia (37%), and nausea (30%). Injection site reactions (eg, injection site pain, erythema) occurred in 32%, with the majority being low grade. Infections (eg, pneumonia, bronchitis) occurred in 51%. Treatment-related grade 3/4 hematologic AEs included thrombocytopenia (52%), neutropenia (31%), anemia (30%), leukopenia (12%), and febrile neutropenia (11%). The most common treatment-related grade 3/4 nonhematologic AE was fatigue (4.3%). Overall, there were 34 (16%) grade 3/4 infections (12 CP, 11 AP, 11 BP). Conclusions: In the largest safety analysis to date, subcutaneous omacetaxine 1.25 mg/m 2 showed an acceptable safety profile in all phases of CML. AEs were primarily hematologic, and grade 3/4 nonhematologic AEs were not common. Support: Teva Pharmaceutical Industries Ltd.
A comparison of tumor characteristics between ER+/PR+ and ER+/PR- breast tumors in Chinese women
Authors: L. Zhou, W. Yin, J. Lu, D. Shi, G. Liu, G. Di, J. Wu, K. Shen, H. Lu, Z. Shen, Z. Shao
Journal: Journal of Clinical Oncology (2007)

21097 Background: Although breast caner patients with any one of the two sex hormone receptors positive can be treated with endocrine therapy, many clinical data showed that there was different response to endocrine therapy for patients with ER+/PR+ and with ER+/PR- tumors. The aim of this study was to find out the factors related to PR expression by comparing the ER+/PR+ tumors and ER+/PR- tumors clinically and biologically. Methods: Between January 1990 to August 2006, 5,191 female breast cancer patients with known ER/PR expression status who received operation in our hospital were enrolled onto this retrospective study. Clinical and biological features of 2,227 patients with ER+/PR+ tumors were compared with those of 909 patients with ER+/PR- tumors. χ 2 test was used for univariate analysis and logistic regression for multivariate analysis. Disease-free survival (DFS) and overall survival (OS) was calculated using Kaplan-Meier analyses, and all statistical tests were two-sided. Results: The peak onset age of patients with ER+/PR+ tumors and ER+/PR- tumors was 50, and it was significantly higher than that of patients with ER- tumors, which is 48(P=0.001). Univariate analysis showed that ER+/PR- tumors were larger in size, had more lymph nodes of metastasis, were higher in tumor grade than ER+/PR+ tumors. Furthermore, the expression of ER and CathepsinD was significantly lower, and CerbB-2 expression was higher in ER+/PR- tumors than in ER+/PR+ tumors. Multivariate analysis indicated that positive PR expression was associated with the level of ER(OR=1.792, P=0.000), CathepsinD(OR=1.380, P=0.035)and CerbB-2(OR=0.639, P=0.007). DFS(P=0.004) and OS(P=0.009) were higher among patients with PR-expressing tumors than with PR- negative tumors. Conclusions: ER+/PR+ tumors and ER+/PR- tumors may have the same etiology which is different from that of ER- tumors. Because of low ER level and changes of the expression of CerbB-2 and CathepsinD, the tumors that lacked PR expression display more aggressive features and have worse prognosis. According to these differences, new target of therapy and endocrine regimen may provide the possibility of improving the response and prognosis of endocrine therapy for patients with ER+/PR- tumors. No significant financial relationships to disclose.
Multicenter randomized phase II trial of methotrexate (MTX) and temozolomide (TMZ) versus MTX, procarbazine, vincristine, and cytarabine for primary CNS lymphoma (PCNSL) in the elderly: An Anocef and Goelams Intergroup study.
Authors: Antonio Marcilio Padula Omuro, Oliver L. Chinot, Luc Taillandier, Herve Ghesquieres, Carole Soussain, Vincent Delwail, Thierry Lamy, Remy Gressin, Sylvain Choquet, Pierre-Louis Soubeyran, Jean Philippe Maire, Alexandra Benouaich Amiel, Sophie Lebouvier-Sadot, Emmanuel Gyan, Maryline Barrie, Monica Sierra del Rio, Alberto Gonzalez, Caroline Houillier, Marie-Laure Tanguy, Khê Hoang-Xuan
Journal: Journal of Clinical Oncology (2013)

2032 Background: There is no standard chemotherapy defined in PCNSL. Elderly patients (pts) are not candidates for whole brain radiotherapy and therefore establishing an optimal MTX-based regimen is crucial. This prospective multicenter study conducted in 13 French institutions tested two promising MTX-based chemotherapy regimens in elderly pts with newly diagnosed PCNSL. Methods: Pts with histologically confirmed newly diagnosed PCNSL with age ≥60 and KPS ≥40 were stratified by institution and KPS, then randomized to receive three 28-day cycles of MTX (3.5 g/m 2 D1 and D15) and TMZ (100-150mg/m2 D1-5 and 15-19) [MT arm] or 3 cycles of MTX (3.5 g/m 2 D1 and D15), procarbazine 100mg/m 2 (D1-7), vincristine (1.4mg/m2 D1 and 15), followed by cytarabine consolidation (3g/m 2 /d X2d) [MPV-A arm]. Neither arm included radiotherapy; prophylactic G-CSF and standardized corticosteroids (methylprednisolone 60mg/d D1-5) were given to both arms. The primary endpoint was PFS (one-stage Fleming design; α= 5%; β=10%). Evaluations included neuropsychological testing and quality of life. Results: Accrual has been completed (7/2007- 3/2010), with 98 pts randomized and 95 analyzed (MT: 48 pts; MPV-A: 47). Pre-treatment characteristics were well balanced between the two arms (all pts: median age=72- range 60-85; median KPS= 70; range 40-100). In the MPV-A arm, the CR rate = 62% (vs 45% in MT arm [p=0.11]), objective response rate= 82% (vs 71%; p=0.23), median PFS= 9.5m (vs 6.1m; HR= 1.14- 95% CI [0.72 ; 1.81]; p=0.6) and median OS= 31m (vs 13.8m; HR= 1.4 - 95% CI [0.84 ; 2.34]; p=0.2). The incidence of grades 3-4 toxicities was 72% in the MPV-A vs 71% in the MT arm. Abnormal liver function test was the most common toxicity (MPV-A: 18 pts; MT: 21). Baseline cognitive impairment (MMSE &gt;24 vs ≤24) predicted OS (p=0.04). Conclusions: This is the first randomized PCNSL study testing two different MTX-based combination regimens. In this elderly population, toxicities were frequent but similar in both arms, and all efficacy endpoints tended to favor the MPV-A arm. The MPV-A regimen is recommended for further development in PCNSL. Clinical trial information: NCT00503594.
Couples symptom burden in oncology care: Perception of self and the other.
Authors: Gabriel Lopez, Kathrin Milbury, Yisheng Li, Minxing Chen, Casey Dutton, Yousra Hashmi, Eduardo Bruera, Lorenzo Cohen
Journal: Journal of Clinical Oncology (2017)

213 Background: Cancer survivors and their caregivers have symptoms that wax and wane over time and are interrelated. We report on the results of a communication survey exploring symptom burden in couples presenting for care in an integrative oncology (IO) clinic. Methods: Couples were approached for participation while waiting for an IO service (Physician Consultation, Massage, Acupuncture, Physical Therapy, Nutrition). 50 patients and their partner completed the Edmonton Symptom Assessment Scale (ESAS; 0-10, 10 worst). Patient and partner each completed two ESAS forms: one for themselves and one for their perception of the other’s symptoms. Each also completed a Global Health scale (PROMIS 10). ESAS distress subscales analyzed included Psychological (PSS) and Physical (PHS). Paired t-tests were used to examine all measures. Results: Patients (58% female) had most frequent cancer diagnoses of breast (22%) and gastrointestinal (18%). Patients rated their own physical symptoms of Fatigue (p = 0.002), Nausea (p &lt; 0.001), Drowsiness (p = 0.032), Appetite (p = 0.008), and Shortness of Breath (p = 0.001) significantly higher than their partner’s rating of their symptoms. Patient self-rating for psychosocial symptoms of anxiety and depression was not significantly different from partner rating of patient symptoms. Partners were more accurate rating psychological symptoms (ESAS PSS, patient 3.89 vs partner 3.72, p = 0.836) and less accurate interpreting physical symptoms (ESAS PHS, patient 16.43 vs partner 9.94, p &lt; 0.001). Except for Sleep, Financial Distress, and Spiritual Pain, partners rated all their own symptoms significantly lower compared to patient’s rating of them (all p’s &lt; 0.001). Patients reported significantly lower global health (36.9 vs 42.9, p &lt; 0.001) and physical health (16.6 vs 20.2, p &lt; 0.001); no differences were observed for mental health for patients vs caregivers (14.2 vs 15.12, p = 0.1). Conclusions: Our findings suggest that partners may better perceive psychological stressors expressed by patients but may be less sensitive to physical symptoms. Interventions aimed at assisting caregivers in better understanding patient physical symptom burden are warranted.
Two doses of NGR-hTNF (N) given alone or in combination with doxorubicin (D) in soft tissue sarcomas (STS).
Authors: Stefano Ferrari, Paolo Giovanni Casali, Jean-Yves Blay, Giuseppe Tonini, Axel Le Cesne, Nasim Ali, Vittorio Perfetti, Emanuela Palmerini, Elena Palassini, Isabelle Ray-Coquard, Bruno Vincenzi, Julien Domont, Emanuela Marchesi, Andrea Marrari, Philippe Alexandre Cassier, Marianna Silletta, Silvia Stacchiotti, Antonio Lambiase, Claudio Bordignon
Journal: Journal of Clinical Oncology (2013)

10568 Background: N, a tumor-targeted antivascular agent, displays a biphasic dose response curve with activity shown at low dose (LD) or high dose (HD). Vascular effects involve at LD an early vessel stabilization that enhances intratumor D uptake followed by late vessel damage and at HD a rapid vessel disruption. Methods: STS patients (pts), stratified by prior D dose (&gt; vs ≤ 300 mg/m 2 ), were randomized to N alone given at LD (0.8 μg/m 2 ) in arm A and at HD (45 μg/m 2 /d1/q1w) in B, or combined with D (60 mg/m 2 /d1/q3w/6 cycles) at LD in arm C and at HD in D. Primary aim of this 4-arm phase II trial was progression free survival (PFS) with CT scans performed q6w until progressive disease (PD). Using 2-stage design, each regimen was rejected if ≤ 2/14 and ≤ 7/24 pts were PD free at 3 months after 1st and 2nd stage, respectively (β=20%, α=10%, n=96). Secondary aims: adverse events (AEs), response rate by RECIST criteria and early metabolic response (MR), as quantified by fractional change in SUV using FDG-PET according to EORTC criteria Results: 66 pts have been enrolled and 55 were included in 1st study stage analysis: median age: 57 yrs; male: 30; PS ≥ 1: 26; leiomyosarcomas: 12; median prior lines: 3 (range, 0-7). In all, 488 weekly cycles were given (mean, 9; range, 1-45). Main grade 3/4 AEs were: neutropenia 18%, chills 7%. After first study stage, primary endpoint was met only in arm C (LD N + D), with 7/14 pts PD free at 3 months. Median PFS was 1.3 months (95% CI, 1.1-1.5) for arm A, 1.5 (1.1-1.8) for B, 4.5 (3.6-5.4) for C and 1.3 (1.1-1.5) for D (p=.01 for trend). By RECIST, there were no objective responses and 20/48 (42%) evaluable pts had stable disease (SD), including 1/12 in arm A, 6/12 in B, 9/12 in C and 4/12 in D. Median SD duration in arm C was 5.5 months (95% CI, 3.7-7.3). By FDG-PET imaging done after 3 weeks, 7/30 (23%) assessable pts had partial MR (4 SD/3 PD per RECIST), with mean change in SUV of -34% (SD, ± 12), while 18 pts (60%) had stable MR (7 SD/11 PD per RECIST), with mean change in SUV of 2% (± 11). Median PFS was 4.2 months in pts who achieved partial MR and 1.5 months in pts who did not (HR=0.67). Complete follow-up for arm C and central histology/radiology review are under way. Conclusions: LD NGR-hTNF plus D is safe, with promising activity as measured by FDG-PET. Clinical trial information: NCT00484341.
Multivariate prognostic factors in metastatic uveal melanoma (UM).
Authors: Ayham Deeb, Nagla Abdel Karim, Philip D. Leming, Ananta Bhatt, Tariq Namad, Changchun Xie, Jillian Hunt, Zelia Correa, James Augsburger
Journal: Journal of Clinical Oncology (2015)

e20105 Background: UM is the rarest subset of all melanomas and has a distinct molecular pathogenesis. Once metastasis develop, the prognosis becomes very poor, however, overall survival (OS) is not the same among all patients with metastatic UM and thus another multivariate prognostic index in metastatic disease is needed. Methods: In aim to identify multi-variables that can influence the OS in metastatic UM, we retrospectively reviewed patient’s and disease characteristics at the time of diagnosis and at the time of detecting metastasis including the intervals between events. Results: A cohort of 42 patients (22 male and 20 female) with mean age of 62 was studied. The primary tumor was exclusively choroidal in 59,5% and involving the ciliary body in 40,5% of patients. All patients had metastatic disease, 54,8% with only hepatic involvement, 26,2% with hepatic and extra-hepatic involvement and 9,5% with extra-hepatic involvement only. The mean interval between initial date of eye treatment and initial date of metastasis detection was 34,73 months while the mean interval from initial treatment until date of death or last follow up was 51 months. The median OS of this cohort was 9,5 months and was longer in females comparing to males (P = 0.0041). The patients with interval to metastasis detection of < 24 months had less survival comparing to patients with interval of > 24 months, (P = 0.0015). Having only extra-hepatic metastasis was associated with better survival comparing to only hepatic or hepatic and extra-hepatic disease, 29,6 months, 9,3 months and 9,8 months, respectively (P = 0.022). The influence of age at date of metastasis detection was not statistically significant. Furthermore, having exclusively choroidal versus tumor involving the ciliary body did not predict survival, 11.7 m and 9.3 m, respectively (P = 0.34). Conclusions: Metastatic UM is associated with a very poor prognosis. In our cohort, the short interval for development of metastasis and liver metastasis significantly worsened the OS, while patients with extra-hepatic lesions only and females had longer OS. Additional factors may prove to be univariate significant prognostic factors for survival time following detection of metastasis.
Preserving fertility for adolescent and young adult cancer survivors: A community model.
Authors: Stephanie L. Lawrence, Karen H. Albritton, Emily Berry, Aurelio Rodriguez, Keith Edward Argenbright
Journal: Journal of Clinical Oncology (2017)

109 Background: Loss of fertility is a significant late effect of cancer treatment for those patients diagnosed during their reproductive years. This loss is a source of considerable distress for patients who have not yet started or completed building their families. Fertility preservation counseling to discuss reproductive concerns regardless of treatment phase can ease this burden. However, due to access- and health-related barriers, approximately half of oncologists report having never referred a patient for a fertility consultation, and as many as 60% of cancer survivors do not recall receiving this information from their healthcare team at time of diagnosis. Methods: The Moncrief Cancer Institute (MCI) Fertility Preservation Program synchronizes services between oncology care providers and fertility specialists. This model is designed to remove discomfort associated with discussing options while enhancing access to care by arranging physician and patient education opportunities specific to fertility preservation and the treatment options available, patient care coordination for fertility preservation treatment, and financial assistance for fertility preservation treatment for underinsured and uninsured adolescent and young adult cancer patients. Results: Referrals for fertility counseling have been provided from 5 institutions through an established referral network comprised of non-profit organizations, local hospitals, and private practice providers. MCI partners with 2 reproductive specialty care groups who offer treatment at reduced rates, which MCI further subsidizes based on financial need. No patients are turned away for inability to pay. The institutions that MCI has targeted for education and partnerships support an environment that meet the distinct needs of adolescent and young adult patients with cancer. Conclusions: Program impact is evaluated by the number of patients and providers receiving education, and the number of patients receiving care coordination and/or financial support for fertility preservation treatment. In the fight against cancer, MCI is assisting patients to protect their future families through fertility preservation education and care coordination.
Cytoreductive surgery for intestinal cancer patients metastatic to the adnexal presenting as primary ovarian cancer.
Authors: Zafer Arik, Omer Dizdar, Mahmut Emre Yildirim, Emre Ozgu, Murat OZ, Serdar gokay Terzioglu, Tayfun Gungor
Journal: Journal of Clinical Oncology (2015)

e14651 Background: For patients with unresectable, and nonobstructing metastatic colon cancer, chemotherapy is the primary treatment option. Despite combination regimens, median overall survival in patients with peritoneal carcinomatosis is about 15 months. The purpose of this study is to evaluate the role of cytoreductive surgery in colon and small intestine cancer patients with metastases to adnexal. Methods: Twenty-six patients with intestinal cancers metastatic to adnexal operated as primary ovarian cancer in Zekai Tahir Burak Women Health Hospital, Gynecologic Oncology Unit between 2008 and 2014 years were retrospectively evaluated. Data were obtained from pathology reports and patients’ records. Demographic and clinical characteristics, and median survival were analyzed Results: Of a total of 26 patients were included, the majority was colon cancer (n = 24) and the remaining was small intestine (n = 2). Median age was 54 years. Most common presenting symptom was abdominal distention (80%). Optimal cytoreduction was performed in 21 patients. Twelve of pathology reports were mucinous adenocarcinoma. Right-sided colon was in 8 patients, rectosigmoid and appendix were, 7 and 7 patients, respectively. Isolated ovarian metastases was found in 6 patients, the remaining 20 patients had peritoneal carcinomatosis. Snychronous liver metastases was found in two patients. Median follow-up was 19 months (range = 3,0-46,9 months). In total, 9 patients died. Only one patient died with isolated ovarian metastases. The remaining 8 exitus were with peritoneal carcinomatosis. Estimated median overall survival was 37.3 months (95% CI = 12.7-61.9 months). Median overall survival of patients who underwent cytoreductive surgery was not reached, compared with 18.5 months for patients with suboptimal cytoreductive surgery (p = 0.012). Conclusions: Cytoreductive surgery may has beneficial effect in selected patients with intestinal cancer metastatic to the adnexal. There is need for randomized clinical trials which address risks and benefits of cytoreductive surgery in intestinal cancers.
Haemodilution in acute stroke: Results of the Italian haemodilution trial
Authors: L. Candelise, R. Colombo, M. Rango, G. Pinardi, C. Fieschi, C. Argentino, F. Giubilei, M. Rasura, S. Cappellari, A. Casazza, L. Grilli, C. P. Warlow, R. Peto, A. Morabito
Journal: The Lancet (1988)
Erratum: Reducing endoplasmic reticulum stress through a macrophage lipid chaperone alleviates atherosclerosis
Authors: Ebru Erbay, Vladimir R Babaev, Jared R Mayers, Liza Makowski, Khanichi N Charles, Melinda E Snitow, Sergio Fazio, Michelle M Wiest, Steven M Watkins, MacRae F Linton, Gökhan S Hotamisligil
Journal: Nature Medicine (2010)
A multicenter phase II study of vorinostat in patients (pts) with relapsed or refractory indolent B-cell non-Hodgkin lymphoma (B-NHL) or mantle cell lymphoma (MCL).
Authors: Kiyoshi Ando, Michinori Ogura, Tatsuya Suzuki, Kenichi Ishizawa, Sung Yong Oh, Won Seog Kim, Yoshinobu Tanaka, Takashi Shimamoto, Kensei Tobinai
Journal: Journal of Clinical Oncology (2012)

8029 Background: Most pts with indolent B-NHL relapse even after rituximab-containing chemotherapy. Vorinostat is an orally active histone deacetylase (HDAC) inhibitor, and is under investigation as monotherapy or in combination regimens in various hematologic malignancies. It has been reported that the histone acetyltransferase genes (EP300 and CREBBP) are frequently mutated in NHL, suggesting the potential usefulness of HDAC inhibitors in its treatment. Methods: We conducted a phase 2 study to investigate the efficacy, safety and tolerability of vorinostat in pts with indolent B-NHL or MCL with the overall response rate (ORR) against follicular lymphoma (FL) as the primary endpoint. The primary hypothesis was to demonstrate the efficacy in FL pts as measured by the ORR. Assuming the true ORR with vorinostat of 50% and without vorinostat of less than 25%, 39 pts will provide 90% power to demonstrate an ORR&gt;25%. Vorinostat was administered at the dose of 200 mg BID for 14 consecutive days in a 21-day cycle. The ORR and PFS were determined by an independent review panel in the Full Analysis Set (FAS) population. Results: A total of 56 pts with a median age of 60 years (range: 33 - 75) were enrolled, and 50 of them (39 with FL, 11 with other subtypes of indolent B-NHL or MCL) were included in the FAS population. The number of prior therapeutic regimens was 2 (range: 1 - 4) and 41 pts have previously received rituximab-based regimens.. The percentages of pts with FLIPI at low risk, intermediate risk and high risk were 41%, 39%, and 21%, respectively. The ORR in 39 pts with FL was 49% (95% CI: 32, 65), and the pre-specified statistical success criterion was met. The median PFS in 39 pts with FL was 17.5 months (range: 2, 22+), especially the median PFS in 19 responders with FL has not yet been reached. The major toxicities were hematologic and gastrointestinal ones, which were reversible and manageable. Grade 3/4 infection was observed in 2%. Conclusions: This phase 2 study demonstrated that oral vorinostat is an agent with sustained antitumor activity in pts with relapsed or refractory indolent B-NHL, with acceptable safety profiles, warranting further investigations.
Complementary Role of CMR to Conventional Screening in the Diagnosis and Prognosis of Cardiac Sarcoidosis
Authors: Vasileios Kouranos, George E. Tzelepis, Aggeliki Rapti, Sofia Mavrogeni, Konstantina Aggeli, Marousa Douskou, Sanjay Prasad, Nikolaos Koulouris, Petros Sfikakis, Athol Wells, Elias Gialafos
Journal: JACC. Cardiovascular imaging (2017)