Overall survival and histology-specific subgroup analyses from a phase 3, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma.

BACKGROUND: We performed a randomized phase 3 study of trabectedin versus dacarbazine in previously-treated patients with liposarcoma/leiomyosarcoma (LPS/LMS). METHODS: Patients were randomized 2:1 to trabectedin (n = 384) or dacarbazine (n = 193) administered intravenously every 3 weeks. The primary objective was overall survival (OS). Secondary objectives were progression-free survival, objective response rate, safety, and patient-reported outcomes, all previously reported and demonstrating superior disease control with trabectedin. Results of the final OS analysis in preplanned subgroups of patients with LPS/LMS are presented. RESULTS: At the time of the final OS analysis, 577 patients had been assigned randomly, including 423 (73%) with LMS and 154 (27%) with LPS. The median duration of treatment exposure was higher in the trabectedin arm compared with the dacarbazine arm (4 vs 2 cycles), as was the proportion of patients receiving an extended number of therapy courses (≥6 cycles: 42% vs 22%). This pattern was consistent across histological subgroups: the median number of treatment cycles (4 vs 2 for both subgroups) and proportion of patients with ≥6 treatment cycles (LMS, 43% vs 24%; LPS, 40% vs 16%). Despite improved disease control by trabectedin, no improvement in OS was observed; the final median OS for trabectedin versus dacarbazine was 13.7 versus 13.1 months (P = .49). Sensitivity analyses of OS suggest confounding by post-study anticancer therapies, which were utilized in most patients in both treatment arms (71% vs 69%, respectively). CONCLUSION: The final OS results demonstrated comparable survival between LPS/LMS patients receiving trabectedin or dacarbazine, which is consistent with the interim analysis results. Both LPS and LMS demonstrated improved disease control with trabectedin.

Results of a prospective phase 2 study of pazopanib in patients with advanced intermediate-grade or high-grade liposarcoma.

BACKGROUND: This phase 2, single-arm, multicenter study was designed to determine the treatment activity and safety of single-agent pazopanib in patients with unresectable or metastatic liposarcoma. METHODS: Eligible patients had high-grade or intermediate-grade liposarcoma with measurable tumors that were unresectable or metastatic, documented disease progression, and had received any number of prior treatments, excluding previous treatment with a vascular endothelial growth factor inhibitor or a tyrosine kinase inhibitor. Patients received oral pazopanib 800 mg once daily for 28-day cycles. Tumor response was evaluated by local radiology assessments every 3 cycles. The primary endpoint was the progression-free rate (PFR) at 12 weeks (PFR12). RESULTS: Forty-one patients were enrolled. The PFR12 was 68.3% (95% confidence interval [CI], 51.9%-81.9%), which was significantly greater than the null hypothesis value of 40% (P = .0002). At 24 weeks, 39% of patients (95% CI, 24.2%-55.5%) remained progression free, and 44% experienced tumor control (partial response or stable disease). The median progression-free survival was 4.4 months (95% CI, 3.2-6.5 months), and the median overall survival was 12.6 months (95% CI, 8.5-16.2 months). The most common adverse events overall were nausea (39%), hypertension (36.6%), diarrhea (34.1%), and fatigue (29.3%), which were typically less than grade 3. There were 5 deaths on study (12.2%), 3 of which were from possible complications of therapy. CONCLUSIONS: The current study provides evidence of potential activity of pazopanib in the liposarcoma subset of patients with soft tissue sarcoma that was specifically excluded from the phase 3 PALETTE trial of other soft tissue sarcoma types. Cancer 2017;123:4640-4647. © 2017 American Cancer Society.

Clinical outcomes of patients with advanced gastrointestinal stromal tumors: safety and efficacy in a worldwide treatment-use trial of sunitinib.

BACKGROUND: The objectives of this study were to provide sunitinib to patients with gastrointestinal stromal tumor (GIST) who were otherwise unable to obtain it and to collect broad safety and efficacy data from a large population of patients with advanced GIST after imatinib failure. (ClinicalTrials.gov identifier NCT00094029). METHODS: Imatinib-resistant/intolerant patients with advanced GIST received sunitinib on an initial dosing schedule of 50 mg daily in 6-week cycles (4 weeks on treatment, 2 weeks off treatment). Tumor assessment frequency was according to local practice, and response was assessed by investigators according to Response Evaluation Criteria in Solid Tumors version 1.0. Overall survival (OS) and safety were assessed regularly. Post hoc analyses evaluated different patterns of treatment management. RESULTS: At final data cutoff, 1124 patients comprised the intent-to-treat population, and 15% of these patients had a baseline Eastern Cooperative Oncology Group performance status ≥2. The median treatment duration was 7.0 months. The median time to tumor progression was 8.3 months (95% confidence interval [CI], 8.0-9.4 months), the median OS was 16.6 months (95% CI, 14.9-18.0 months), and 36% of patients were alive at the time of analysis. Patients for whom the initial dosing schedule was modified exhibited longer median OS (23.5 months) than those who were treated strictly according to the initial dosing schedule (11.1 months). The most common treatment-related grade 3 and 4 adverse events were hand-foot syndrome (11%), fatigue (9%), neutropenia (8%), hypertension (7%), and thrombocytopenia (6%). Treatment-related adverse events associated with cardiac function (eg, congestive heart failure and myocardial infarction) were reported at frequencies of ≤1% each. CONCLUSIONS: This treatment-use study confirms the long-term safety and efficacy of sunitinib in a large international population of patients with advanced GIST after imatinib failure.

Childhood anxiety and psychophysiological reactivity: hypnosis to build discrimination and self-regulation skills.

Clinically anxious, worried, and fearful children and teens need clinicians' assistance in reducing their exaggerated psychophysiological stress reactivity. Affective neuroscience finds that chronic activation of the body's emergency response system inhibits neurogenesis, disrupts neuronal plasticity, and is detrimental to physical and mental health. Patterns of faulty discrimination skills, for example, over-estimation of threat and danger and under-estimation of their coping capacity, fuel this over-arousal. Similarly, contributory patterns of reduced self-regulation skills are shown by "stuck" attention to and poor control of their exaggerated psychophysiological reactivity and somatization. This article considers the literature and focuses on cognitive hypnotherapy to enhance these under-developed capacities. A case illustration highlights various hypnotic phenomena and techniques, psychoeducation, and relaxation training that address the goals of interrupting these unproductive, interconnected patterns and fostering new patterns of more realistic and accurate discrimination capacities and sturdier psychophysiological self-regulation skills.

Childhood anxiety, worry, and fear: individualizing hypnosis goals and suggestions for self-regulation.

Determining hypnosis goals and specific suggestions for childhood anxiety, worry, and fear can be enhanced by a developmental psychopathology perspective. This article examines underlying causal risk factors that guide a focused assessment and individualized interventions, targeting self-regulation of emotional, cognitive, behavioral, and psychophysiological arousal and reactivity. The author summarizes current knowledge about childhood anxiety disorders and outlines a hypnotic approach when encountering anxious children and youth, including strategies to use spontaneous trance states and enhance underdeveloped resources (e.g. locus of control, discrimination of realistic risk appraisal, coping capacities).

Metastatic Carcinomatosis Cirrhosis: A Rare Pattern of Metastasis.

Metastatic carcinomatosis cirrhosis is a pattern of metastasis in which malignancy infiltrates the liver and provokes hepatic fibrosis. It is an especially rare complication of several malignancies, including breast cancer. We report a case of a 61-year-old woman with lobular carcinoma of the breast who presented with confusion and rising serum tumor markers without evidence of disease recurrence on imaging. She subsequently developed clinical evidence of hepatic dysfunction and a liver biopsy revealed diffuse infiltration of the liver by breast carcinoma with surrounding fibrous tissue deposition, consistent with metastatic carcinomatosis cirrhosis. This case highlights a rare and clinically significant pattern of metastasis and is the first to describe lobular carcinoma of the breast causing metastatic carcinomatosis cirrhosis.

Integrating Pediatric Hypnosis with Complementary Modalities: Clinical Perspectives on Personalized Treatment.

While pediatric integrative medicine (PIM) emphasizes an "evidence-based practice using multiple therapeutic modalities"; paradoxically, literature reviews examining the prevalence and/or efficacy of such mind⁻body approaches often address PIM modalities separately. Such contributions are relevant, yet documentation of how to deliver combined complementary approaches in children and youth are scarce. Nevertheless, integrative practitioners in clinical practice routinely mix approaches to meet the individual needs of each patient. Best practices are flexible, and include blending and augmenting services within the same session, and/or connecting modalities sequentially for an incremental effect, and/or referring to outside resources for additional interventions. Resonating with integrative medicine's definition, this article's goal is to demonstrate paradigms that "bring together complementary approaches in a coordinated way within clinical practice" by linking clinical hypnosis, the trail-blazer modality in PIM's history, with mindfulness, biofeedback, acupuncture, and yoga. Following the consideration of the overlap of guided imagery with hypnosis and an abridged literature report, this clinical perspective considers the selection of modalities within a collaborative relationship with the child/teen and parents, emphasizing goodness-of-fit with patients' contexts, e.g., symptoms, resources, interests, goals, and developmental stage. Case vignettes illustrate practical strategies for mixing approaches.

State-of-the-Art Pediatric Hypnosis Training: Remodeling Curriculum and Refining Faculty Development.

Training in pediatric hypnosis has been part of clinical hypnosis education in the United States since 1976. Workshops expanded over time and are now taught by highly experienced pediatric clinicians across the globe. In 1987, a small vanguard of North American faculty, academic pediatricians, and pediatric psychologists taught a 3-day pediatric hypnosis workshop at the national meeting of the Society for Developmental and Behavioral Pediatrics (SDBP). This model of annual tri-level concurrent workshops (introductory, intermediate, and advanced) was sponsored by the SDBP for 24 years. In 2009, the National Pediatric Hypnosis Training Institute (NPHTI) assembled, and in 2010, offered its first annual workshops. This article documents this history of pediatric hypnosis education and describes NPHTI's remodeling and ongoing refinement toward a state-of-the-art curriculum with innovative methodology based upon (1) current research about adult experiential and small group learning; (2) design principles for presentations that maximize adult learning and memory; and (3) evaluations by participants and faculty. These underpinnings-including clinical training videos, individualized learning choices, emphasis on personalized, goal-oriented sessions, and advances in faculty selection, and ongoing development-are applicable to adult training models. Integration of developmental and self-regulation strategies may be more unique to pediatric hypnosis skills training programs. The conclusion proposes expansion of pediatric hypnosis education and elimination of related barriers toward goals that all children learn self-hypnosis (SH) for mind-body health.

Clinical Hypnosis with Children and Adolescents-What? Why? How?: Origins, Applications, and Efficacy.

This review article addresses the process, intention, and therapeutic value of clinical hypnosis with children and adolescents. A brief historical perspective is followed by a digest of the published laboratory and clinical research that has accelerated substantially over the past two decades. This review lends appropriate credence to the benefits and integration to clinical practice of this powerful tool for teaching young people self-regulation skills. The breadth of application is described, and several clinical vignettes are provided as examples of what is possible. In addition to the provision of the most relevant citations in the pediatric, psychological, and neuroscience literature, this synopsis concludes with information regarding availability of skill development training in pediatric clinical hypnosis.