Nine-Week Versus One-Year Trastuzumab for Early Human Epidermal Growth Factor Receptor 2â € "Positive Breast Cancer: 10-Year Update of the ShortHER Phase III Randomized Trial

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We present the final analysis of the phase III noninferiority, randomized ShortHER trial comparing 9 weeks versus 1 year of adjuvant trastuzumab with chemotherapy in patients with human epidermal growth factor receptor 2â € "positive (HER2+) early breast cancer (BC). Women with HER2+ BC were randomly assigned to anthracycline-taxane combinations plus 1-year trastuzumab (arm A, long) or 9-week trastuzumab (arm B, short). Here, we report the second coprimary end point overall survival (OS), updated disease-free survival (DFS), and outcomes according to hormone receptor status, age, and nodal status. At a median follow-up of 9 years, 10-year DFS is 77% versus 78% in the long versus short arm, respectively. Ten-year OS is 89% versus 88% in the long versus short arm, respectively. 10-year DFS rates in the long versus short arm according to nodal status are N0 81% versus 85%; N1-3 77% versus 79%; and N4+ 63% versus 53%. Ten-year OS rates in long versus short arm according to nodal status are N0 89% versus 95%%; N1-3 92% versus 89%; and N4+ 84% versus 64%. The updated analysis of the ShortHER trial shows that 1-year trastuzumab is the standard treatment for patients with HER2+ early BC as noninferiority cannot be claimed. However, numerically, the differences for the patients at low or intermediate risk (N0/N1-3) is negligible, while patients with N4+ have a clear benefit with 1-year trastuzumab

The Still Bay points of Apollo 11 Rock Shelter, Namibia : an inter-regional perspective

Abstract: Dating to roughly 80,000 to 70,000 years ago, components of the Still Bay technocomplex of southern Africa and their potential behavioural implications have been widely discussed. Stone points with invasive retouch, as defined over 90 years ago by Goodwin and van Riet Lowe, serve as markers for Still Bay assemblages, yet many Still Bay sites remain undated and comprehensive, comparable sets of data for their point assemblages remain unpublished. Much of the Middle Stone Age at the site of Apollo 11 in Namibia was undated until 2010, when a potential Still Bay component was announced. Although a Still Bay assemblage at Apollo 11 would represent the most northwesterly and inland expression of this technocomplex, its points have never been fully analysed. This paper presents their morphometric data and an interpretation of point-production strategies. These results are then compared with data obtained for two South African sites: Hollow Rock Shelter in the Western Cape and Umhlatuzana in KwaZulu-Natal. This comparison demonstrates that whereas there are no statistically significant differences in the morphometric data sets between the three sites, there are both similarities and differences in point-production strategies, cross-section shapes and the use of raw materials for knapping. It is suggested that these similarities and variations represent aspects of how knowledge-transfer systems and knapping conventions were followed on both intra-regional and inter-regional scales

Lithic technological responses to Late Pleistocene glacial cycling at Pinnacle Point Site 5-6, South Africa

There are multiple hypotheses for human responses to glacial cycling in the Late Pleistocene, including changes in population size, interconnectedness, and mobility. Lithic technological analysis informs us of human responses to environmental change because lithic assemblage characteristics are a reflection of raw material transport, reduction, and discard behaviors that depend on hunter-gatherer social and economic decisions. Pinnacle Point Site 5-6 (PP5-6), Western Cape, South Africa is an ideal locality for examining the influence of glacial cycling on early modern human behaviors because it preserves a long sequence spanning marine isotope stages (MIS) 5, 4, and 3 and is associated with robust records of paleoenvironmental change. The analysis presented here addresses the question, what, if any, lithic assemblage traits at PP5-6 represent changing behavioral responses to the MIS 5-4-3 interglacial-glacial cycle? It statistically evaluates changes in 93 traits with no a priori assumptions about which traits may significantly associate with MIS. In contrast to other studies that claim that there is little relationship between broad-scale patterns of climate change and lithic technology, we identified the following characteristics that are associated with MIS 4: increased use of quartz, increased evidence for outcrop sources of quartzite and silcrete, increased evidence for earlier stages of reduction in silcrete, evidence for increased flaking efficiency in all raw material types, and changes in tool types and function for silcrete. Based on these results, we suggest that foragers responded to MIS 4 glacial environmental conditions at PP5-6 with increased population or group sizes, 'place provisioning', longer and/or more intense site occupations, and decreased residential mobility. Several other traits, including silcrete frequency, do not exhibit an association with MIS. Backed pieces, once they appear in the PP5-6 record during MIS 4, persist through MIS 3. Changing paleoenvironments explain some, but not all temporal technological variability at PP5-6.Social Science and Humanities Research Council of Canada; NORAM; American-Scandinavian Foundation; Fundacao para a Ciencia e Tecnologia [SFRH/BPD/73598/2010]; IGERT [DGE 0801634]; Hyde Family Foundations; Institute of Human Origins; National Science Foundation [BCS-9912465, BCS-0130713, BCS-0524087, BCS-1138073]; John Templeton Foundation to the Institute of Human Origins at Arizona State Universit

Androgen receptor in triple negative breast cancer: A potential target for the targetless subtype

13nononenoneGerratana, L.; Basile, D.; Buono, G.; De Placido, S.; Giuliano, M.; Minichillo, S.; Coinu, A.; Martorana, F.; De Santo, I.; Del Mastro, L.; De Laurentiis, M.; Puglisi, F.; Arpino, G.*Gerratana, L.; Basile, D.; Buono, G.; De Placido, S.; Giuliano, M.; Minichillo, S.; Coinu, A.; Martorana, F.; De Santo, I.; Del Mastro, L.; De Laurentiis, M.; Puglisi, F.; Arpino, G

Histopathological grading affects survival in patients with IDH-mutant grade II and grade III diffuse gliomas

Background: Diffuse grade II and grade III gliomas are actually classified in accordance with the presence of isocitrate dehydrogenase mutation (IDH-mut) and the deletion of both 1p and 19q chromosome arms (1p/19q codel). The role of tumour grading as independent prognostic factor in these group of tumours remains matter of debate. The aim of this study was to determine if grade is an independent prognostic factor and not somehow associated to IDH mutation and 1p/19q status of the tumour. Methods: We analysed 399 consecutive patients with newly diagnosed, histologically proven World Health Organisation (WHO) 2016 grade II or grade III IDH-mut gliomas, assessed by polymerase chain reaction, immunohistochemistry or next-generation sequencing (NGS). Results: The analysis included 399 patients with grade II (n = 250, 62.7%) or grade III (n = 149, 37.3%) diffuse gliomas. Median follow-up time was 105.3 months. Median survival was 148.1 months. In multivariate analysis, grade II (hazard ratio [HR] = 0.342, 95% confidence interval [CI]: 0.221\u20130.531; P < 0.001) and 1p/19q codeletion (HR = 0.440, 95% CI: 0.290\u20130.668; P < 0.001) were independently associated with a lower risk for death. The difference in survival remained significant (p = 0.006 in astrocytomas, p = 0.014 in oligodendrogliomas) when adjusted for histological subtype. Residual disease after surgery (or biopsy) negatively affected survival (HR: 2.151, 95% CI: 1.375\u20133.367, P = 0.001). Post-surgical treatment with radiotherapy + adjuvant chemotherapy improved survival compared with follow-up and other treatments (HR: 0.316, 95% CI: 0.156\u20130.641, P = 0.001). Conclusions: In our study, histopathological grade still affects survival in IDH-mutant WHO grade II and III diffuse gliomas. This effect appears to be independent from molecular features, extension of surgical resection and post-surgical treatments. Therefore, physicians should continue to take into account tumour grade, along their molecular characteristics, for a better clinical and therapeutic management of the patients

IDH wild type low grade gliomas: Who seeks shall find

Background: The 2016 WHO classification of CNS tumors included molecular parameters in addition to histology to redefine many tumor entities. Low-grade glioma (LGG) are divided into isocitrate dehydrogenase (IDH) wild type or mutant. Absence of IDH mutation is a rare event in LGG, and IDH wild type are considered a provisional entity. The technique used to assess IDH mutation is essential to determine the real impact of this tumor type. Methods: The observation of a particularly favorable outcome in a group of 42 patients with a diagnosis of IDH wild type LGG (OS= 93.7 months) led us to retest IDH mutation with a more sensitive technique. Next Generation Sequencing (NGS) was used to retest IDH status in tumor samples, the results of NGS assay were compared with previous findin

82,000-year-old shell beads from North Africa and implications for the origins of modern human behavior

The first appearance of explicitly symbolic objects in the archaeological record marks a fundamental stage in the emergence of modern social behavior in Homo. Ornaments such as shell beads represent some of the earliest objects of this kind. We report on examples of perforated Nassarius gibbosulus shell beads from Grotte des Pigeons (Taforalt, Morocco), North Africa. These marine shells come from archaeological levels dated by luminescence and uranium-series techniques to ≈82,000 years ago. They confirm evidence of similar ornaments from other less well dated sites in North Africa and adjacent areas of southwest Asia. The shells are of the same genus as shell beads from slightly younger levels at Blombos Cave in South Africa. Wear patterns on the shells imply that some of them were suspended, and, as at Blombos, they were covered in red ochre. These findings imply an early distribution of bead-making in Africa and southwest Asia at least 40 millennia before the appearance of similar cultural manifestations in Europe

The role of clinical and molecular factors in low-grade gliomas: What is their impact on survival?

Aim: To evaluate relevance of clinical and molecular factors in adult low-grade gliomas (LGG) and to correlate with survival. Methods: We reviewed records from adult LGG patients from 1991 to 2015 who received surgery and had sufficient tissue to molecular biomarkers characterization. Results: 213 consecutive LGG patients were included: 17.4% were low-risk, according to Radiation Therapy Oncology Group (RTOG) risk assessment. IDH 1/2 mutation, 1p/19q co-deletion, MGMT methylation were found in 93, 50.8 and 65.3% of patients. Median follow-up was 98.3 months. In univariate analysis, overall survival was influenced by extent of resection (p = 0.011), IDH mutation (p < 0.001), 1p/19q co-deletion (p = 0.015) and MGMT methylation (p = 0.013). In multivariate analysis, RTOG clinical risk (p = 0.006), IDH mutation (p < 0.001) and 1p/19q co-deletion (p = 0.035) correlated with overall survival. RTOG clinical risk (p = 0.006), IDH mutation (p < 0.001) and 1p/19q co-deletion (p = 0.035) correlated with overall survival. Conclusion: Both clinical and molecular factors are essential to determine prognosis and treatment strategies

The role of clinical and molecular factors in low-grade gliomas: what is their impact on survival?

AIM: To evaluate relevance of clinical and molecular factors in adult low-grade gliomas (LGG) and to correlate with survival. METHODS: We reviewed records from adult LGG patients from 1991 to 2015 who received surgery and had sufficient tissue to molecular biomarkers characterization. RESULTS: 213 consecutive LGG patients were included: 17.4% were low-risk, according to Radiation Therapy Oncology Group (RTOG) risk assessment. IDH 1/2 mutation, 1p/19q co-deletion, MGMT methylation were found in 93, 50.8 and 65.3% of patients. Median follow-up was 98.3 months. In univariate analysis, overall survival was influenced by extent of resection (p = 0.011), IDH mutation (p < 0.001), 1p/19q co-deletion (p = 0.015) and MGMT methylation (p = 0.013). In multivariate analysis, RTOG clinical risk (p = 0.006), IDH mutation (p < 0.001) and 1p/19q co-deletion (p = 0.035) correlated with overall survival. RTOG clinical risk (p = 0.006), IDH mutation (p < 0.001) and 1p/19q co-deletion (p = 0.035) correlated with overall survival. CONCLUSION: Both clinical and molecular factors are essential to determine prognosis and treatment strategies