tbuckley/cabot-search huggingface dataset:
Post hoc analysis of sustained efficacy/tolerability of ≥12 cycles of omacetaxine mepesuccinate in chronic myeloid leukemia (CML).
Authors: Delphine Rea, Hagop M. Kantarjian, Meir Wetzler, Franck E. Nicolini, Jeffrey H. Lipton, Luke Paul Akard, Hanna Jean Khoury, Mauricette Michallet, Agnès Guerci-Bresler, Charles Chuah, Andrzej Hellmann, Laurence Legros, Krzysztof Warzocha, Purvish M. Parikh, Adam Craig, Jorge E. Cortes
Journal: Journal of Clinical Oncology (2013)

7066 Background: Subcutaneous omacetaxine mepesuccinate (OMA), a first-in-class cephalotaxine, inhibits protein synthesis independent of Bcr-Abl signaling. It showed clinical activity in 2 phase II, open-label CML trials, 1 in patients with a T315I Bcr-Abl mutation failing imatinib, and 1 in patients failing ≥2 tyrosine kinase inhibitors (TKIs). Methods: This post hoc analysis pooled patients with chronic phase (CP) or accelerated phase (AP) from the 2 trials. 28-day cycles of OMA 1.25 mg/m 2 BID were given ≤14 days for induction, ≤7 days as maintenance with dose delay/change as needed. Primary endpoints were major cytogenetic response (MCyR) for CP and complete hematologic response (CHR) for AP. Adverse events (AEs) were assessed. Results: Of 108 CP and 51 AP patients from the 2 trials, 31 (29%) CP and 7 (14%) AP patients received ≥12 cycles (Table). At baseline in the ≥12-cycle groups, most CP (median age 59 y) and AP patients (median age 67 y) had received hydroxyurea (17/31, 4/7) and ≥2 TKIs (22/31, 5/7), were not in CHR (22/31, 5/7), and were T315I positive (23/31, 3/7). As of March 31, 2012, 9 CP and 2 AP patients continued OMA treatment. Overall, mean days dosed per cycle were 6.1 for CP, 9.7 for AP; 5.3 and 8.9 at cycle 12. Grade 3/4 AEs occurred in 35/38 patients in this post hoc analysis, most in early cycles; 15/31 CP, 2/7 AP had grade ≥3 AEs first occurring at ≥12 cycles. Across all cycles, most common grade ≥3 AEs were thrombocytopenia (24/31 CP, 5/7 AP), anemia (16/31, 7/7), and neutropenia (17/31, 3/7).Nine patients receiving ≥12 cycles (5/31, 4/7) discontinued, most commonly due to disease progression (n=2). Conclusions: In this post hoc analysis of heavily pretreated CML-CP and CML-AP patients who had failed prior TKI therapy, efficacy was often durable for those who received OMA for ≥12 cycles. Most grade 3/4 AEs were hematologic and declined with time. Support: Teva BPP R and D, Inc. Clinical trial information: NCT00375219, NCT00462943.
Palliative intra-arterial high-dose cisplatin for inoperable sarcoma.
Authors: Marcus Paulo Fernandes Amarante, Jessica Ribeiro Gomes, Carolina Kawamura, Rafael Schmerling, Tercia Tarciane Soares de Sousa, Raphael Brandao Moreira, Antonio C. Buzaid, Marcos Andre De Sa Barreto Costa, Fernando C. Maluf, Renata D'Alpino D'Alpino
Journal: Journal of Clinical Oncology (2015)

e21521 Background: Inoperable sarcoma may be associated with limiting local symptoms . To date, there are no data regarding the efficacy of palliative intra-arterial cisplatin for unresectable sarcoma. Methods: We retrospectively reviewed all patients with unresectable symptomatic sarcoma who underwent at least one course of palliative superselective intra-arterial chemotherapy with high-dose cisplatin (150 mg/m2/week) treated by the authors from 2004 to 2014. Sodium thiosulfate was administered intravenously to minimize cisplatin side effects. Progression-free survival (PFS) was calculated by the Kaplan Meier method. Objetive responses were reported according to the attending physician´s evaluation. Results: A total of 10 patients (6 males) were included in the analysis. Median age was 53 (range: 23-74). Histologic subtypes included chondrosarcomas (2), 1 chordoma (1), angiosarcoma (1), liposarcoma (1), 1 alveolar rhabdomyosarcoma (1), osteosarcoma (1), epithelioid sarcoma (1), 1 spindle cell sarcoma (1) and pleomorphic sarcoma (1). Treated anatomic sites included nasal clivus (1), gluteal muscle (2), sacrum (2), mastigatory space (1), supraclavicular fossa (1), mediastinum (1), thigh (1) and face (1). Number of cycles ranged from 1 to 5. Three patients received concomitant radiation therapy while 3 had received it previously. Five patients had significant objective tumor responses, as documented by imaging studies. Median PFS was 1.9 months. Four patients had tumor control for more then 3 months. Only 3 patients experienced adverse events (1 reversible acute renal failure, 1 grade 2 nausea and 1 hearing loss). Conclusions: Intra-arterial high-dose cisplatin with thiosulfate rescue was well-tolerated and produced significant palliation in approximately half of the patients treated. This strategy should be further evaluated in prospective trials.
Cardiac Myxoma
Authors: Abdallah El Sabbagh, Mohammed A. Al-Hijji, Jeremy J. Thaden, Sorin V. Pislaru, Cristina Pislaru, Patricia A. Pellikka, Adelaide M. Arruda-Olson, Martha Grogan, Kevin L. Greason, Joseph J. Maleszewski, Kyle W. Klarich, Vuyisile T. Nkomo
Journal: JACC. Cardiovascular imaging (2017)
Chemotherapy-induced febrile neutropenia (FN) and FN prevention strategies in cancer care in the U.S. Veterans Health Administration (VHA).
Authors: Richard L. Barron, Li Wang, Onur Baser, Wendy J. Langeberg, David C. Dale
Journal: Journal of Clinical Oncology (2013)

6608 Background: Chemo-induced FN can be a life-threatening adverse event requiring immediate hospitalization and is associated with increased infection-related mortality and healthcare costs. Because the VHA has a fully-integrated national claims database, we used this database to assess FN incidence, burden, and prevention strategies in VA cancer patients. Methods: VHA’s database includes de-identified inpatient, outpatient, pharmacy, and laboratory claims and EMR data. Patients ≥ 18 years old with lung, colorectal (CRC), or prostate cancer or non-Hodgkin lymphoma (NHL) who had initiated ≥ 1 course of myelosuppressive chemo from Jan 2006–Sept 2011 were included. Endpoints included chemo treatment patterns and FN incidence, burden (inpatient mortality, length of stay [LOS], and costs), and prophylaxis. FN was identified based on ICD-9-CM codes for neutropenia. Prophylaxis was defined as first use of any granulocyte colony-stimulating factor (G-CSF) or intravenous antibiotics within 5 days of chemo administration or oral antibiotics within 7 days before and 6 days after chemo administration in any cycle. Costs were estimated using hospital and laboratory claims containing an FN diagnosis. Results: 27,899 patients were eligible and were included in the analysis. Most were ≥ 65 years old (56%) and male (98%). See Table for selected endpoints. Conclusions: FN was a common event, and patients with FN had lengthy hospital stays, high inpatient mortality rates, and considerable costs. In the VHA, antibiotic prophylaxis was generally used more frequently than G-CSF prophylaxis. [Table: see text]
Survivorship care plans: Processes, effective strategies, and challenges in a rural state.
Authors: Mary Isaacson, Polly Hulme, Jenna Cowan, Jennifer Kerkvliet, Mary Minton, Lexi Pugsley
Journal: Journal of Clinical Oncology (2017)

47 Background: Annually, South Dakota (SD) averages nearly 4,000 new cancer cases with over 40,000 cancer survivors residing in the state. While the cancer incidence and survivorship rates in SD may be similar to the rest of the nation, SD’s unique geographic and demographic landscape offers challenges in cancer survivorship care. The purpose of this presentation is to illustrate the development and implementation of cancer survivorship care plans (SCP) at three health systems in the rural state of SD. Each of these health systems is unique in its history, culture, and infrastructure. Collectively, they serve most cancer patients living in SD. Methods: An observational qualitative design was used. Key players at each health system were interviewed using a structured interview. The interviews were audio-recorded and transcribed. The authors synthesized the transcriptions with member-checking completed for each system. Results: Processes for development and implementation of SCPs similar across health systems were (a) gathering a leadership team or making a designated staff role for survivorship care, (b) developing a SCP template(s), (c) provider/staff in-put and endorsement, and (d) tracking and identifying patients for scheduling and receipt. On the other hand, the health systems approached SCP completion and delivery differently. For example, at one health system multiple individuals from the patient’s care team were responsible for SCP population and completion. Effective strategies across health systems comprised incorporating prior SCP work, open communication, and standardization of SCPs with flexibility in implementation. Challenges included incompatibilities of electronic health record platforms for automatic SCP template population and adequate staffing for the complexities of enacting SCPs. Key findings suggest a process framework is beneficial for the development and implementation of SCPs. Conclusions: As health systems consider developing and implementing SCPs, consideration of the following recommendations for a process framework may be helpful: building a foundation, gathering resources, reviewing the evidence, eliciting input, and implementing in stages.
Outcomes among patients with isolated myeloid sarcoma: A SEER database analysis.
Authors: Maryam Movassaghian, Andrew Mark Brunner, Traci M. Blonquist, Ashmeet Bhatia, Donna S. Neuberg, Hossein Sadrzadeh, Amir Tahmasb Fathi
Journal: Journal of Clinical Oncology (2014)

7075 Background: Myeloid sarcoma (MS) is a rare extramedullary presentation of acute myeloid leukemia (AML), which can involve a number of primary locations. MS can exist concurrently with marrow involvement or as an isolated phenomenon. Little is known about outcomes in isolated MS due to its rarity. We performed an analysis of isolated MS using the Survival, Epidemiology, and End Results (SEER) database. Methods: Using the SEER database, we identified 339 patients, aged ≥ 15 diagnosed with isolated MS between 1973-2010. Overall survival (OS) was calculated as the time from diagnosis to death or censored at last visit or study cutoff (12/31/2010). OS was compared between non-MS-AML and MS using the log-rank test, and estimated by site of presentation using the Kaplan and Meier method. Involved sites were categorized as: head/neck, gastrointestinal (GI) mucosa, chest/abdomen, pelvis/genitourinary (GU), lymphatics/spleen, soft tissue, skin, bones, nervous system, eyes/gonads. Results: Median age at diagnosis was 64 for patients with MS and 67 for patients with AML. The 30-day mortality rate was lower for patients with MS compared to AML (0.11 vs. 0.23, p<0.0001). OS was significantly higher for MS than for AML (3-year: 0.319 vs. 0.172, p<0.0001). OS varied by the site of involvement. Data for primary sites of disease in the Pelvis/GU, GI mucosa, and eyes/gonads suggest better survival at 6 months compared to involvement of the nervous system, lymphatics/spleen, or soft tissue (Table). Conclusions: Population-based survival for patients with isolated MS appears to be superior to AML. MS outcomes vary depending on site of involvement; patients with disease in the pelvis/GU, GI mucosa, and in the eyes/gonads, may have relatively better survival. Number Median Age Male (%) OS at 6 Months Overall Non MS AML 49,039 67 54 0.441 [0.437-0.446] MS 339 64 55 0.57 [0.51-0.62] Disease Site Head/Neck 40 64 53 0.64 [0.47-0.77] GI Mucosa 31 50 65 0.74 [0.55-0.86] Chest/Abdomen 29 58 52 0.62 [0.42-0.77] Pelvis/GU 21 55 24 0.95 [0.71-0.99] Lymphatics/Spleen 45 65 56 0.40 [0.26-0.54] Soft Tissue 93 66 53 0.45 [0.34-0.55] Skin 32 74 66 0.61 [0.41-0.76] Bone 17 56 47 0.53 [0.28-0.73] Nervous System 11 69 45 0.24 [0.04-0.53] Eyes/Gonads 20 56 85 0.80 [0.56-0.92]
Downstaging after preoperative chemoradiation as a prognostic marker for recurrence after curative surgery in locally advanced rectal cancer.
Authors: Jieun Lee, Myung Ah Lee, Sang Woo Kim, Jun Ki Kim, Seong Taek Oh, Won Kyung Kang, HongSeok Jang
Journal: Journal of Clinical Oncology (2013)

e14650 Background: 5-fluorouracil (5-FU) based preoperative concurrent chemoradiation (CCRT) with surgery is the standard treatment for resectable rectal cancer. Chemotherapy after surgery improves local control, but there are some debates for the role in 5-FU based adjuvant chemotherapy. This study was aimed to analyze the tumor recurrence pattern in locally advanced rectal cancer, and the relationship between clinicopathologic factors with tumor recurrence. Methods: One hundred forty-nine patients with locally advanced rectal cancer, receiving preoperative 5-FU based CCRT (radiation dose: 5040 cGy) with total mesorectal excision (TME), followed by adjuvant 5-FU based chemotherapy were enrolled. Sex ratio was 95:54. Median age was 61 (range 37~83). Medical records were reviewed retrospectively. Clinicopathologic factors, oncologic outcomes (tumor recurrence, disease free survival (DFS)) were assessed. Results: Median follow-up duration was 25.3 months (range 5.2~66.2). Median DFS was 19.3 months (range 0~63.4). Thirty-five (23%) patients showed recurrence after surgery. Among tumor recurrence, 86% of patients were presented with distant metastases. Absence of T or N downstaging after 5-FU CCRT was significantly correlated with tumor recurrence (P=0.032 and P=0.011 by Fisher’s exact test, respectively) and longer DFS (P=0.003 and P&lt;.001 by Kaplan-Meier survival curve, respectively). Lymphatic invasion, neural invasion after 5-FU CCRT showed correlation with recurrence (HR=6.37, 95% CI; 2.74-14.84, P&lt;.001; HR=4.9, 95% CI; 1.85-12.97, P=0.002, respectively). In contrast, vascular invasion was not associated with tumor relapse after 5-FU CCRT followed by surgery. Conclusions: The absence of T or N downstaging, the presence of lymphatic or perineural invasion in pathology was associated with tumor recurrence. In spite of 5-FU based adjuvant chemotherapy, distant metastases were more prevalent. In patients with the possibility of distant metastases, more aggressive adjuvant chemotherapy-including platinum agents-should be considered.
Analysis of imatinib (IM)-related, low-grade (LG), non-hematologic (heme) adverse events (AEs) in patients (pts) with chronic myeloid leukemia (CML) switched to nilotinib (NIL): ENRICH study update.
Authors: Michael J. Mauro, Jeffrey Howard Lipton, Carole Brennan Miller, Sikander Ailawadhi, Lambert Busque, Luke Paul Akard, Javier Pinilla-Ibarz, Solveig Ericson, Felice Lin, Jorge E. Cortes
Journal: Journal of Clinical Oncology (2012)

6605 Background: This study update assesses change in chronic LG non-heme AEs in adult Ph+ CML-CP pts switched from IM to NIL. Methods: Pts were eligible if treated with IM 400 mg/d for ≥3 mo, and had IM-related grade (G) 1/2 non-heme AEs persisting ≥2 mo or recurring ≥3 times and persisting despite best supportive care. Pts received NIL 300 mg BID. Primary endpoint is change in IM-related LG non-heme AEs at 3 mo. Disease response was monitored by RQ-PCR and pt-reported outcomes measured by 2 quality-of-life (QoL) questions and MD Anderson Symptom Inventory (MDASI)-CML. Results: 47 pts were enrolled as of data cut-off (11/14/2011). There were 168 baseline IM-related non-heme AEs: 121 G1, 47 G2. 37 pts completed 3 mo NIL, by 3 mo 103 of 154 IM-related AEs (67%) improved (92 resolved, 11 improved from G2 to G1), 47 unchanged, 4 increased in severity. 13 pts were dose reduced for NIL-related AEs; 8 pts re-escalated after AEs recovered to G1 or resolved. 34 G3 AEs occurred in 15 pts; investigators reported 19 AEs as suspected NIL-related (increased bilirubin, lipase, or blood glucose; hypokalemia; hypophosphatemia; pruritus; bronchitis; dehydration; rash; arthralgia; pleural effusion). 8 pts discontinued NIL: 6 for AEs, 2 withdrew consent. No G4 AEs were reported. 32 pts had MMR (3-log reduction of Bcr-Abl; ≤0.1% IS) at entry; 16 additional pts achieved MMR on NIL. At entry, 18 pts had 4-log reduction and 10 pts 4.5-log reduction in Bcr-Abl. 16 and 13 additional pts achieved 4- and 4.5-log reduction, respectively, on NIL. At 3 mo (n=34) 62% and 53% pts reported QoL improvement from baseline in the previous 24 h and 7 d, respectively. Reduction in MDASI-CML severity/interference scores indicates symptom improvement. Mean reductions in MDASI-CML from baseline at 3 mo: severity, 1.21 (n=34); interference, 1.55 (n=33). Conclusions: 3 mo after switching to NIL, ~70% baseline chronic LG non-heme IM-related AEs improved and ≥53% of pts reported improvement in QoL. Molecular responses were maintained or improved in all patients. Switch from IM to NIL in majority of pts reduces IM-related toxicities and preserves/induces molecular response in CML-CP.
A phase II, open-label, multicenter trial to investigate the clinical activity and safety of avelumab (MSB0010718C) in patients with metastatic Merkel cell carcinoma.
Authors: Howard Kaufman, Omid Hamid, Sandra P. D'Angelo, Guojun Yuan, Kevin M. Chin, Shailender Bhatia, Jean-Marie Cuillerot, Paul Nghiem
Journal: Journal of Clinical Oncology (2015)

TPS9086 Background: The programmed death-1 receptor (PD-1) and its ligand (PD-L1) are key therapeutic targets in the reactivation of the immune response against multiple cancers. Avelumab* (MSB0010718C) is a fully human anti-PD-L1 IgG1 antibody currently being investigated in clinical trials. Merkel cell carcinoma (MCC) is a rare, aggressive, Merkel cell polyomavirus (MCPyV)-induced skin cancer with suboptimal therapeutic options. Cytotoxic chemotherapy is commonly used to treat metastatic MCC, although responses are seldom durable. There is a strong rationale for investigating PD-1/PD-L1 blockade in MCC. Despite their immunogenicity, MCC tumors are able to evade the host immune system through multiple mechanisms that include exhaustion of tumor virus-specific T cells via expression of PD-L1 on the tumor cells and adjacent immune-cell infiltrates. Methods: This is a multicenter, international, single-arm, open-label, phase II trial to evaluate the efficacy and safety of avelumab in patients (pts) with metastatic MCC who have received ≥ 1 prior line of chemotherapy. Up to 84 eligible pts will receive avelumab at a dose of 10 mg/kg as a 1h intravenous (IV) infusion Q2W. Treatment will continue until disease progression, unacceptable toxicity, or if criterion for treatment withdrawal is met. Primary objective is to assess the clinical activity of avelumab as determined by the objective response rate (ORR) according to RECIST 1.1 by an Independent Endpoint Review Committee. Secondary objectives include assessment of the duration of response, progression-free survival time (PFS), overall survival (OS), and safety. The pharmacokinetic (PK) profile of avelumab will also be evaluated. Exploratory objectives include assessment of immune-related responses and evaluation of PD-L1 expression and its potential association with response rate. This study will also explore the quality of life of pts with MCC who have been treated with avelumab. The trial is in progress: 19 of a planned 84 patients have been recruited (trial start June 2014, estimate end January 2017). NCT02155647. *Proposed INN. Clinical trial information: NCT02155647.
ENESTnd 5-year (y) update: Long-term outcomes of patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) treated with frontline nilotinib (NIL) versus imatinib (IM).
Authors: Richard A. Larson, Dong-Wook Kim, Saengsuree Jootar, Ricardo Pasquini, Richard E. Clark, Clarisse Lobo, Stuart L. Goldberg, Hirohiko Shibayama, Andreas Hochhaus, Giuseppe Saglio, Hagop M. Kantarjian, Charisse Kemp, Weiping Deng, Hans D. Menssen, Timothy P. Hughes
Journal: Journal of Clinical Oncology (2014)

7073 Background: In ENESTnd, NIL has shown superior efficacy vs IM. Here, we report data based on a minimum follow-up of 5 calendar y. Methods: Pts with newly diagnosed CML-CP were randomized to NIL 300 mg twice-daily (BID; n = 282), NIL 400 mg BID (n = 281), or IM 400 mg once-daily (QD; n = 283). P values for secondary efficacy endpoints were not adjusted for multiple comparisons and are provided for descriptive purposes only. Results: At the data cutoff, 60%, 62%, and 50% of pts in the NIL 300 mg BID, NIL 400 mg BID, and IM arms, respectively, remained on core treatment. Over half of pts in the NIL arms achieved MR4.5 (BCR-ABLIS ≤ 0.0032%) by 5 y, and MR4.5 rates were significantly higher on NIL vs IM overall and within each Sokal risk group (Table). Rates of major molecular response (MMR; BCR-ABLIS ≤ 0.1%), freedom from progression to accelerated phase/blast crisis (AP/BC), and overall survival (OS) were higher on NIL vs IM. Fewer pts treated with NIL vs IM died from advanced CML. The safety profiles of NIL and IM were as expected. The rates of cardiovascular events (CVEs) of interest remained highest on NIL 400 mg BID and lowest on IM. Conclusions: NIL continues to result in superior efficacy vs IM in pts with CML-CP. NIL was generally well tolerated; however, CVEs of interest were more common on NIL vs IM. Clinical trial information: CAMN107A2303. NIL 300 mg BID n = 282 NIL 400 mg BID n = 281 IM 400 mg QD n = 283 MR4.5 by 5 y, % (P vs IM) 54 (< .0001) 52 (< .0001) 31 Low Sokal risk 53 (.0148) 62 (.0002) 37 Intermediate Sokal risk 60 (< .0001) 50 (.0126) 33 High Sokal risk 45 (.0041) 42 (.0105) 23 MMR by 5 y, % (P vs IM) 77 (< .0001) 77 (< .0001) 60 5-y freedom from progression to AP/BC, % (P vs IM)a 96 (.0403) 98 (.0028) 92 5-y OS, % (P vs IM)a 94 (.4881) 96 (.0266) 92 Deaths from advanced CML, n (P vs IM)b 6 (.0292) 4 (.0057) 16 Safety population n = 279 n = 277 n = 280 5-y CVE rates, n (%) Ischemic heart disease 11 (4) 24 (9) 5 (2) Ischemic cerebrovascular events 4 (1) 9 (3) 1 (< 1) Peripheral artery disease 7 (3) 7 (3) 0 aKaplan-Meier estimate, including events after discontinuation. bPts for whom the principal cause of death (during treatment or follow-up) was "study indication" or "unknown" or not reported but subsequent to a documented progression to AP/BC.