Survey and analysis of the usefulness of the social studies guide for New Hampshire elementary schools

Thesis (Ed.M.)--Boston Universit

A Phase II Basket Trial of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART SWOG 1609) in Patients with Nonpancreatic Neuroendocrine Tumors.

PurposeImmune checkpoint blockade has improved outcomes across tumor types; little is known about the efficacy of these agents in rare tumors. We report the results of the (nonpancreatic) neuroendocrine neoplasm cohort of SWOG S1609 dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART).Patients and methodsWe performed a prospective, open-label, multicenter phase II clinical trial of ipilimumab plus nivolumab across multiple rare tumor cohorts, with the (nonpancreatic) neuroendocrine cohort reported here. Response assessment by grade was not prespecified. The primary endpoint was overall response rate [ORR; RECIST v1.1; complete response (CR) and partial response (PR)]; secondary endpoints included progression-free survival (PFS), overall survival (OS), stable disease >6 months, and toxicity.ResultsThirty-two eligible patients received therapy; 18 (56%) had high-grade disease. Most common primary sites were gastrointestinal (47%; N = 15) and lung (19%; N = 6). The overall ORR was 25% [95% confidence interval (CI) 13-64%; CR, 3%, N = 1; PR, 22%, N = 7]. Patients with high-grade neuroendocrine carcinoma had an ORR of 44% (8/18 patients) versus 0% in low/intermediate grade tumors (0/14 patients; P = 0.004). The 6-month PFS was 31% (95% CI, 19%-52%); median OS was 11 months (95% CI, 6-∞). The most common toxicities were hypothyroidism (31%), fatigue (28%), and nausea (28%), with alanine aminotransferase elevation (9%) as the most common grade 3/4 immune-related adverse event, and no grade 5 events.ConclusionsIpilimumab plus nivolumab demonstrated a 44% ORR in patients with nonpancreatic high-grade neuroendocrine carcinoma, with 0% ORR in low/intermediate grade disease

Paradoxical Infrastructures: Ruins, Retrofit, and Risk

In recent years, a dramatic increase in the study of infrastructure has occurred in the social sciences and humanities, following upon foundational work in the physical sciences, architecture, planning, information science, and engineering. This article, authored by a multidisciplinary group of scholars, probes the generative potential of infrastructure at this historical juncture. Accounting for the conceptual and material capacities of infrastructure, the article argues for the importance of paradox in understanding infrastructure. Thematically the article is organized around three key points that speak to the study of infrastructure: ruin, retrofit, and risk. The first paradox of infrastructure, ruin, suggests that even as infrastructure is generative, it degenerates. A second paradox is found in retrofit, an apparent ontological oxymoron that attempts to bridge temporality from the present to the future and yet ultimately reveals that infrastructural solidity, in material and symbolic terms, is more apparent than actual. Finally, a third paradox of infrastructure, risk, demonstrates that while a key purpose of infrastructure is to mitigate risk, it also involves new risks as it comes to fruition. The article concludes with a series of suggestions and provocations to view the study of infrastructure in more contingent and paradoxical forms

Bone Biomarkers and Subsequent Survival in Men with Hormone-sensitive Prostate Cancer: Results from the SWOG S1216 Phase 3 Trial of Androgen Deprivation Therapy with or Without Orteronel.

BACKGROUND: Bone biomarkers are strongly prognostic for overall survival (OS) in men with castration-resistant prostate cancer but not fully established for hormone-sensitive prostate cancer (HSPC). OBJECTIVE: Bone biomarkers in HSPC were prospectively evaluated as part of a phase 3 study of androgen deprivation therapy ± the CYP17 inhibitor orteronel. DESIGN, SETTING, AND PARTICIPANTS: Patients were randomly divided into training (n = 316) and validation (n = 633) sets. Recursive partitioning and Cox proportional hazard models were employed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Bone resorption (C-telopeptide and pyridinoline) and bone formation markers (C-terminal collagen propeptide and bone alkaline phosphatase) were assessed from patient sera. RESULTS AND LIMITATIONS: Of 1279 men, 949 had evaluable baseline bone biomarkers. Optimal cutoffs were identified to define elevated levels of each of the four biomarkers (all p \u3c 0.05) that were associated with worse OS. After adjusting for clinical risk factors in the validation set, elevated bone biomarkers were statistically significantly associated with an increased risk of death (hazard ratios ranging from 1.37 to 1.92). Recursive partitioning algorithms applied to the training set identified three risk groups (low, intermediate, and poor) with differential OS outcomes (median OS: 8.2, 5.1, and 2.1 yr, respectively) based on combinations of bone biomarkers. These results were confirmed in the validation set. CONCLUSIONS: In men with HSPC initiating androgen deprivation therapy, bone biomarkers are strongly and independently prognostic for OS. Bone biomarker levels alone or in combination with clinical covariates identify unique subsets of men with differential OS outcomes. These results validate the clinical value of bone biomarker assessment in the HSPC state, extending bone biomarker utility beyond the castration-resistant state. PATIENT SUMMARY: In men with newly diagnosed metastatic prostate cancer, high levels of bone turnover biomarkers are associated with a shorter lifespan

Bone Biomarkers and Subsequent Survival in Men with Hormone-sensitive Prostate Cancer: Results from the SWOG S1216 Phase 3 Trial of Androgen Deprivation Therapy with or Without Orteronel

BackgroundBone biomarkers are strongly prognostic for overall survival (OS) in men with castration-resistant prostate cancer but not fully established for hormone-sensitive prostate cancer (HSPC).ObjectiveBone biomarkers in HSPC were prospectively evaluated as part of a phase 3 study of androgen deprivation therapy ± the CYP17 inhibitor orteronel.Design, setting, and participantsPatients were randomly divided into training (n = 316) and validation (n = 633) sets. Recursive partitioning and Cox proportional hazard models were employed.Outcome measurements and statistical analysisBone resorption (C-telopeptide and pyridinoline) and bone formation markers (C-terminal collagen propeptide and bone alkaline phosphatase) were assessed from patient sera.Results and limitationsOf 1279 men, 949 had evaluable baseline bone biomarkers. Optimal cutoffs were identified to define elevated levels of each of the four biomarkers (all p < 0.05) that were associated with worse OS. After adjusting for clinical risk factors in the validation set, elevated bone biomarkers were statistically significantly associated with an increased risk of death (hazard ratios ranging from 1.37 to 1.92). Recursive partitioning algorithms applied to the training set identified three risk groups (low, intermediate, and poor) with differential OS outcomes (median OS: 8.2, 5.1, and 2.1 yr, respectively) based on combinations of bone biomarkers. These results were confirmed in the validation set.ConclusionsIn men with HSPC initiating androgen deprivation therapy, bone biomarkers are strongly and independently prognostic for OS. Bone biomarker levels alone or in combination with clinical covariates identify unique subsets of men with differential OS outcomes. These results validate the clinical value of bone biomarker assessment in the HSPC state, extending bone biomarker utility beyond the castration-resistant state.Patient summaryIn men with newly diagnosed metastatic prostate cancer, high levels of bone turnover biomarkers are associated with a shorter lifespan

A Phase II Basket Trial of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART SWOG 1609) in Patients with Nonpancreatic Neuroendocrine Tumors.

Background: The potential therapeutic benefits of checkpoint inhibitors and their application to many different tumor types has been a key factor in the advancement of medical oncology since their first approval for metastatic melanoma in 2011. However, their efficacy in rare tumor types remains to be seen. This paper presents the results of combination therapy with both anti-CTLA and anti-PD-1 in the small bowel cohort of SWOG S1609 Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART).Methods: This study is designed as a prospective, open-label, multicenter phase 2 clinical trial of ipilimumab (1mg/kg intravenously every 6 weeks) plus nivolumab (240mg intravenously every 2 weeks) in rare tumors. Here we report the outcomes from patients diagnosed with small bowel cancer (SBC). The primary endpoints included overall response rate (ORR) (RECIST v1.1) (complete response (CR) and partial responses (PR)); progression-free survival (PFS), overall survival (OS), stable disease \u3e6 months, and toxicity were the secondary endpoints.Results: Twenty five patients were registered to the cohort and twenty three received therapy. The duodenum was the primary site of origin in 52% (N=11), 14% (N=3) arose in the ileum and 14% (N=3) arose in the jejunum. The primary site of origin was unknown in 19% (N=4). The overall response rate was 8% (CR, 4%, N= 1; PR, 4%, N= 1). The median PFS was 2 months; 6-month OS was 48% and median OS 6 months. The most common toxicities were diarrhea and fatigue (both 17%) followed by dyspnea (13%) with diarrhea, increased bilirubin, colitis and elevated lipase (all 4.3%) as the most common grade 3-5 immune-related adverse events.Conclusions: Combination therapy with ipilimumab plus nivolumab in small bowel tumors resulted in an overall response rate of 8% with one partial and one complete response in twenty three treated patients

Multicenter phase II trial (SWOG S1609, cohort 51) of ipilimumab and nivolumab in metastatic or unresectable angiosarcoma: a substudy of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART)

PURPOSE: Angiosarcoma is a rare aggressive endothelial cell cancer with high mortality. Isolated reports suggest immune checkpoint inhibition efficacy in angiosarcoma, but no prospective studies have been published. We report results for angiosarcoma treated with ipilimumab and nivolumab as a cohort of an ongoing rare cancer study. METHODS: This is a prospective, open-label, multicenter phase II clinical trial of ipilimumab (1 mg/kg intravenously every 6 weeks) plus nivolumab (240 mg intravenously every 2 weeks) for metastatic or unresectable angiosarcoma. Primary endpoint was objective response rate (ORR) per RECIST 1.1. Secondary endpoints include progression-free (PFS) and overall survival, and toxicity. A two-stage design was used. RESULTS: Overall, there were 16 evaluable patients. Median age was 68 years (range, 25-81); median number of prior lines of therapy, 2. Nine patients had cutaneous and seven non-cutaneous primary tumors. ORR was 25% (4/16). Sixty per cent of patients (3/5) with primary cutaneous scalp or face tumors attained a confirmed response. Six-month PFS was 38%. Altogether, 75% of patients experienced an adverse event (AE) (at least possibly related to drug) (25% grade 3-4 AE); 68.8%, an immune-related AE (irAE) (2 (12.5%), grade 3 or 4 irAEs (alanine aminotransferase/aspartate aminotransferase increase and diarrhea)). There were no grade 5 toxicities. One of seven patients in whom tumor mutation burden (TMB) was assessed showed a high TMB (24 mutations/mb); that patient achieved a partial response (PR). Two of three patients with PDL1 immunohistochemistry assessed had high PDL1 expression; one achieved a PR. CONCLUSION: The combination of ipilimumab and nivolumab demonstrated an ORR of 25% in angiosarcoma, with three of five patients with cutaneous tumors of the scalp or face responding. Ipilimumab and nivolumab warrant further investigation in angiosarcoma. TRIAL REGISTRATION NUMBER: NCT02834013