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Background: Late recurrence of breast cancer after 5 years accounts for about 50% of recurrences in hormone receptor (HR)-positive early breast cancer (EBC). TAILORx established non-inferiority of adjuvant endocrine therapy (ET) given for at least 5 years to chemotherapy plus ET (CET) in EBC and a 21-gene recurrence score (RS) of 11-25, although there was some chemotherapy benefit in women Methods: Eligibility criteria included women 18-75 years with HR-positive, HER2-negative, T1b-T2N0 EBC who agreed to have CT assigned or randomized based on the RS assay. The primary endpoint was invasive disease-free survival (iDFS) in the RS 11-25 group. The “primary analysis” refers to the original prespecified analysis for the primary IDFS endpoint (836 IDFS events at full information in the RS 11-25 group) after a median of 7.5 years. The “updated analysis” was performed after a median followup of 11.0 and 10.4 years in the randomized and overall populations, respectively. Results:10,253 eligible women enrolled between 4/7/06-10/6/10.The updated analysis includes substantially more events that the primary analysis, including IDFS events (1819 vs. 1210), distant recurrences (561 vs. 384), locoregional +/- distant recurrences (764 vs. 543), and deaths (910 vs. 499). The table provides 5 and 12-year event rates (and standard errors) for all arms, and comparisons of the randomized arms. The primary trial conclusions remain unchanged: ET was non-inferior to CET in the randomized group with a RS 11-25. Although recurrence occurred in < 10% by 12 years for a RS 0-25, late recurrence events beyond 5 years exceeded earlier recurrence. Non-recurrence events occurred in about 13% at 12 years (~1%/year), contributing substantially to the IDFS rates. For women Conclusions: The current updated analysis confirms findings from the original primary analysis that ET is non-inferior to CET in HR-positive, HER2-negative, node-negative EBC and a RS 11-25. As in the original primary analysis, the subgroup of women Citation Format: Joseph Sparano, Robert J. Gray, Della Makower, Kathy S. Albain, Daniel F. Hayes, Charles Geyer, Elizabeth Dees, Matthew P. Goetz, John A. Olson Jr, Tracy G. Lively, Sunil Badve, Thomas Saphner, Lynne I. Wagner, Timothy Whelan, Virginia Kaklamani, George Sledge. Trial Assigning Individualized Options for Treatment (TAILORx): An Update Including 12-Year Event Rates [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS1-05.

Uncontrolled studies suggest that the addition of high dose rate intraluminal brachytherapy (HDRIB) to external beam radiotherapy (EBR) may improve palliation for patients with advanced non-small cell lung cancer (NSCLC). The purpose of this study was to evaluate the potential clinical benefit of adding HDRIB to EBR in a multicenter randomized trial.Patients with symptomatic stage III or IV NSCLC with endobronchial disease were randomized to EBR (20Gy in 5 daily fractions or 30Gy in 10 daily fractions) or the same EBR+HDRIB (14Gy in 2 fractions over two weeks). The primary outcome was the proportion of patients who achieved symptomatic improvement in patient-reported overall lung cancer symptoms on the Lung Cancer Symptom Scale (LCSS) at 6 weeks following randomization. Secondary outcomes included improvement in individual symptoms, symptom progression free survival, overall survival and toxicity. The planned sample size was 250 patients based on detection of symptomatic improvement from 40 to 60% with a two-sided α of 0.05 and 80% power.134 patients were randomized over 4.5 years: 67 to each arm. The study closed early due to slow accrual. The mean age was 69.8 years, and 67% had metastatic disease. At six weeks 19 patients (28.4%) in the EBR arm and 20 patients (29.9%) in the EBR+HDRIB arm experienced an improvement in lung cancer symptoms (p=0.84). When limited to patients who completed the LCSS percentages were 40.4% vs 47.6%, respectively, p=0.49. Between group differences in mean change scores (0.3-0.5 standard deviations) in favor of EBR+HDRIB were observed for overall symptoms, but only hemoptysis was significantly improved (p=0.03). No significant differences were observed in progression free or overall survival. Grade 3/4 toxicity was similar between groups.Small to moderate improvements were seen in symptom relief with the combined therapy, but they did not reach statistical significance. Further research is necessary before recommending HDRIB in addition to EBR for palliation of lung cancer symptoms.

The study of print culture and the history of the book in the eighteenth century has benefited significantly in the past three decades from studies that have placed varying degrees of emphasis on the three key components of print culture—author, publisher, and reader—and their interwoven relationships. This scholarship has also spurred new research on the literary and print culture of evangelical Anglicans, Methodists, Quakers, Calvinistic Methodists, Baptists, Moravians, and Independents in Great Britain and America, including specific studies related to the transatlantic nature of the printing histories of Philip Doddridge and Jonathan Edwards. This chapter seeks to further this discussion by exploring three areas of eighteenth-century evangelical print culture in England: the interplay between readers, writers, and producers with informal and formal sources; the ecclesiastical/topographical reconstruction of reading/selling communities of chapel-goers and neighboring (and usually like-minded) booksellers; and the interaction of these two elements in the publishing history of one representative text, Samuel James’s An Abstract of the Gracious Dealings of God with Several Eminent Christians (1760).

As part of its new Friends of the Angus initiative, The Angus Library and Archive has organised a series of online lectures, ‘Opening the Angus’, for Friends to enjoy. In the following report, our ...

Rationale Two antifibrotic medications, nintedanib and pirfenidone, have been approved for the treatment of idiopathic pulmonary fibrosis (IPF) in the US. Few data have been published on the use of these medications in clinical practice. Objective To investigate patterns of use of antifibrotic medications in the US. Methods The IPF-PRO Registry, a multicenter US registry, has enrolled patients with IPF that was diagnosed or confirmed at the enrolling center in the past 6 months. Data from patients enrolled from 5 June 2014 to 4 March 2018 were used to determine antifibrotic medication use ("treatment") in the enrollment window and a follow-up window approximately 6 months later. Associations between patient characteristics and treatment status were tested using logistic regression. Results Overall, 551 of 782 eligible patients (70.5%) were treated in the enrollment window. Younger age, lower FVC % predicted, oxygen use with activity, worse self-rated health based on the Short Form-12 (SF-12) or St George's Respiratory Questionnaire score, referral to the enrolling center by a pulmonologist, use of lung biopsy in diagnosis, and carrying a diagnosis of IPF to the enrolling center were associated with being treated. Among 534 patients treated at enrollment who had follow-up data, 94.0% remained treated in follow-up. Better self-rated health based on the SF-12 mental component score or EuroQoL score, and not using oxygen with activity at enrollment, were associated with continuing treatment in follow-up. Among 172 patients who were untreated at enrollment and had follow-up data, 29.7% started treatment in follow-up. Lower DLco % predicted, a family history of ILD, a history of sleep apnea, and a definite diagnosis of IPF at enrollment were associated with starting treatment in follow-up. Conclusions The majority of patients in the IPF-PRO Registry were receiving an approved medication for IPF at enrollment. Treatment at enrollment was associated with greater disease severity, more compromised quality of life and the use of oxygen with activity. Clinical trial registered with ClinicalTrials.gov (NCT01915511).

Though Baptist historians have placed considerable emphasis upon the lives and careers of prominent ministers, recent archival work has revealed much about the lives, careers, and activities of lay...

A circle of Dissenting women writers that began in the 1770s, centred on Mary Steele of Broughton and Elizabeth Coltman of Leicester, merged in the 1790s in London with a group of Dissenting literary women and men revolving around William Godwin, Mary Hays and Crabb Robinson, a phenomenon revealed almost exclusively through informal life-writings and poems, most of which have remained in manuscript. This cross-pollination of women's literary coteries reveals much about how eighteenth-century women's literary networks were formed and perpetuated, how they overcame geographical boundaries and how they enriched the lives of their members and their male friends.

A fresh examination of the life-writings of Henry Crabb Robinson, which are now being prepared for a new edition, reveals new details about the lives and times of several writers considered "minor" in the 1930's, when Edith Morley prepared her monumental edition, Henry Crabb Robinson on Books and Their Writers (3 vols, 1938). (1) Those volumes have served as the starting and ending point for information (sometimes firsthand, sometimes anecdotal) by Robinson on scores of writers, male and female, from England, America, and Europe gathered during his long life (1775-1867). (2) Mary Hays is an example. Morley inserted eight references by Robinson to Hays in Books and Their Writers: one from his 1799 reminiscences, one from an 1805 letter, three from his diary for 1813, and one from 1817, 1819, and 1843 (1: 5-7, 124-25, 128, 130-31, 212, 234-35; 2: 629; 3:843-44). (3) The exigencies of print precluded Morley, however, from recording all references to Hays by Robinson throughout his voluminous life-writings. Important additions to Morley's work on Robinson and Hays appear in Marilyn Brooks's edition of Hays's correspondence (which includes twelve letters that passed between Hays and Robinson between 1802 and 1842) and Gina Luria Walker's biography of Hays. (4) Robinson's friendship with Hays, however, has been significantly expanded through the uncovering of nearly 180 references to Hays (composed between 1799 and 1859) in Robinson's diary, reminiscences, and correspondence. These references establish Hays as the most dominant woman writer in Robinson's life-writings, a tribute to their friendship as well as his appreciation of Hays's intellect and literary abilities. (5) Robinson's life-writings focus primarily on Hays's activities after 1803, a period Gina Walker called her "buried life" (Mary Hays 234-37) that commenced with Hays's monumental publication, Female Biography, or, Memoirs of Illustrious and Celebrated Women, of All Ages and Countries. Modern editions of Hays's major texts through 1803 illuminate her writing but not her biography. (6) Recovering her bio-text, reconstituting her life within a geographical, social, and religious setting, requires informal sources: diaries, letters, newspaper notices, church books, marriage and death certificates, and detailed genealogical records. For Hays, Crabb Robinson is such a source. As his life-writings become more accessible to scholars, Hays's relationship with Robinson expands in new ways, revealing three fundamental connections between the dedicated diarist and the outspoken feminist: a religious connection as life-long Dissenters; a familial connection through the marriages of two of Hays's nieces to relations (by marriage) of Robinson, marriages that remained strictly within the household of Dissent; and, most important, a cultural connection, one that flourished in the 1790s through the intertwining of several circles of liberal Dissenters and radicals in London and the provinces. These connections became evident in their initial meeting in the spring of 1799, and were further sealed in Robinson's stunning defense of Hays against Charles Lloyd in his letter to Catherine Clarkson the following January, a letter that foreshadows the central features in their enduring friendship that spanned more than forty years. Though known as a heterodox Unitarian and rational Dissenter, Mary Hays was raised an orthodox Calvinist, the third of four daughters of John (c. 1725-74) and Elizabeth Judge Hays (c. 1730-1811) of Gainsford Street, Southwark, near the wharves along the south side of the Thames where the family conducted its business as corn and flour factors and worshiped in the Particular Baptist chapel at the end of the street. (7) Mary's elder sister, Joanna (1754-1805), married John Dunkin (1753-1827) in July, 1774, just three months after the death of Mr. Hays. Mrs. Hays never remarried, living for many years in the family home in Gainsford Street, usually with one or more of her children while conducting business as a wine merchant (Universal British Directory, 1, part 2: 174). …

Jane Attwater’s friendship with Mary Steele was so deep that it served as the model for Danebury, Steele’s narrative poem about “The Power of Friendship” between two young girls about the same age as Steele and Attwater in 1768, the year the poem was composed. After the poem’s publication in 1779, Steele sent Attwater a copy with the fol-lowing inscription: Sylvia cannot transmit this little Pamphlet to the Friend of her heart without reminding her from whom those Ideas of Friendship arose which it feebly attempts to describe without recollecting with enthusiastic tenderness those happy hours when her Myrtilla taught her “Ere she knew its name to feel its Power” & however deficient she is in every other respect her Bosom still glows with the ardent wish of being what Emma was to Elfrida A Faithful Friend[.] (NWW 3: 390, n. 2)

The 14th St Gallen International Breast Cancer Conference (2015) reviewed substantial new evidence on locoregional and systemic therapies for early breast cancer. Further experience has supported the adequacy of tumor margins defined as 'no ink on invasive tumor or DCIS' and the safety of omitting axillary dissection in specific cohorts. Radiotherapy trials support irradiation of regional nodes in node-positive disease. Considering subdivisions within luminal disease, the Panel was more concerned with indications for the use of specific therapies, rather than surrogate identification of intrinsic subtypes as measured by multiparameter molecular tests. For the treatment of HER2-positive disease in patients with node-negative cancers up to 1 cm, the Panel endorsed a simplified regimen comprising paclitaxel and trastuzumab without anthracycline as adjuvant therapy. For premenopausal patients with endocrine responsive disease, the Panel endorsed the role of ovarian function suppression with either tamoxifen or exemestane for patients at higher risk. The Panel noted the value of an LHRH agonist given during chemotherapy for premenopausal women with ER-negative disease in protecting against premature ovarian failure and preserving fertility. The Panel noted increasing evidence for the prognostic value of commonly used multiparameter molecular markers, some of which also carried prognostic information for late relapse. The Panel noted that the results of such tests, where available, were frequently used to assist decisions about the inclusion of cytotoxic chemotherapy in the treatment of patients with luminal disease, but noted that threshold values had not been established for this purpose for any of these tests. Multiparameter molecular assays are expensive and therefore unavailable in much of the world. The majority of new breast cancer cases and breast cancer deaths now occur in less developed regions of the world. In these areas, less expensive pathology tests may provide valuable information. The Panel recommendations on treatment are not intended to apply to all patients, but rather to establish norms appropriate for the majority. Again, economic considerations may require that less expensive and only marginally less effective therapies may be necessary in less resourced areas. Panel recommendations do not imply unanimous agreement among Panel members. Indeed, very few of the 200 questions received 100% agreement from the Panel. In the text below, wording is intended to convey the strength of Panel support for each recommendation, while details of Panel voting on each question are available in supplementary Appendix S2, available at Annals of Oncology online., 0, SCOPUS: ar.j, info:eu-repo/semantics/published

Mary Steele exhibited a lifelong commitment to her poetry and her coterie of female kindred spirits. She also relied heavily upon a particular pastoral persona, hinted at in her first poem, as well as in her choice of the nom de plume “Sylvia,” a name derived from the Latin word “Silvia” (a spelling also used by Steele), which means “woods” or “forest.” In “A Rural Meditation, 1766,” the poet seeks retirement in nature, what Margaret Doody calls the “trope of isolation” with its accompanying moods of melancholy, a “nearly universal” feature of British poetry after 1750 (229).1 In this instance, however, the isolated setting serves as a site from which to bask in the intimacy of female friendship and the pleasures of artistic freedom, merging the solitary and communal into a unified voice unlike the “unitary” voice often associated with Romantic poetry. In those “beauteous sylvan scenes” at her uncle’s estate at Yeovil, Sylvia feels secure enough to allow her “feet” and imagination “to stray,” a security sealed by a pleasing sociability she shares with her fellow-poets Myra and Celia (Mary Scott and Miss Williams) (NWW 3: 51). Mary Steele’s natural, almost earthy, persona—a fiercely independent single woman-poet inspired by a rural muse in a secluded setting shared by a community of female friends—stands in stark contrast to her aunt’s near-beatified role as Theodosia, the heavenly hymn writer.

In 1843, John Holland, in The Psalmists of Britain, boasted, “There are few names of more certain occurrence in modern collections of Psalms and Hymns than that of Mrs. Steele—but still fewer, there is reason to believe, of whom less has been known, even by the majority of those persons who have adopted her compositions.” His reference is to Anne Steele (she never married, despite Holland’s use of “Mrs.”), whose poetry, he adds, “veiled under an assumed name [Theodosia], was comparatively unknown beyond the circle of her personal friends” (2: 223).1 Holland had only a slight understanding of the quality and breadth of the coterie of male and female writers surrounding Anne Steele. Otherwise, he would have known that she was neither “veiled” nor “unknown” in the second half of the eighteenth century, though by 1843 both her poetry and her literary circle were indeed not widely known. Holland’s information on Steele came mostly from Hugh Russell, the minister at the Broughton Baptist Church (1809–49) where the Steele family had worshiped since the late 1600s. Holland did discover one fact during his visit to Broughton that was not known in 1843 beyond the small “circle” familiar with the Steele family, and that was that Anne Steele was not the only talented poet to emerge from her family in the eighteenth century.

Mary Steele’s life and poetry may have been veiled by anonymity and obscurity, but Mary Scott and her major poems, The Female Advocate (1774) and Messiah (1788), have been known for more than two centuries. Nevertheless, Scott’s identity and biography have likewise suffered from misidentification and numerous inaccuracies. Commentators on Scott have relied heavily on information taken from nine letters by Anna Seward (1747–1809) to Scott and one by Seward to her friend William Hayley, all composed between 1786 and 1793 and published in Archibald Constable’s six-volume edition of The Letters of Anna Seward (1811).1 Seward’s letters provide important background about Scott’s reading and literary interests, as well as her health, courtship, and marriage to John Taylor (1752–1817), but Seward’s assertion to Hayley on May 10, 1788, that Scott’s “Father was a Clergyman of the Church of England” (NWW 4: 290) set later commentators on an erroneous path. In the mid-1980s, nearly two hundred years after her death, when Gae Holladay and Moira Ferguson began the pioneering work of resurrecting Mary Scott as a significant eighteenth-century feminist writer, they still used Seward’s letters as a starting point for Scott’s life. To Holladay, Mary Scott was, like Seward, an Anglican Bluestocking “enjoying a literary life among a small circle, composing poems for private circulation or subscription publication, contributing to miscellany volumes … overseeing editions of [her] works, or contributing poems to one of many editions of Poems by Eminent Ladies (1755) or Dodsley’s Collection of Poems (1748)” (iii–iv).

In the mid-1780s the Steele circle expanded beyond the West Country to Leicester, in the Midlands, welcoming Elizabeth Coltman as the final addition to the second generation centered upon Mary Steele. Coltman and her sisters were educated at a boarding school at Stoke Newington, Hackney, possibly the same boarding school Mary Steele attended between 1766 and early 1769, but, if not, one close enough that the girls may have attended the same dissenting chapel (Skillington 8). Most likely Elizabeth came to know Mary Steele through her older sister Anne Coltman (1753–88), who was born the same year as Steele and would have attended school either with Steele or possibly Mary Scott. Elizabeth Coltman was eight years Steele’s junior and it seems unlikely she would have attended boarding school at the same time, although it is possible that in autumn 1768 or the early months of 1769 (Steele’s last term in London), Anne, Elizabeth, and their other sister Mary (1757–1834), at that time aged 15, 11, and 7, could have been attending together. Whatever the case, Steele’s friendship with Coltman flourished in the 1780s, with Coltman evenutally succeeding Mary Scott as Steele’s “kindred soul.”