Long-Term Follow-Up of a Phase I/II Trial of Dose Escalating Three-Dimensional Conformal Thoracic Radiation Therapy with Induction and Concurrent Carboplatin and Paclitaxel in Unresectable Stage IIIA/B Non-small Cell Lung Cancer

BACKGROUND: We conducted a modified phase I/II trial investigating the incorporation of three-dimensional conformal thoracic radiation therapy (TCRT) into the treatment paradigm of induction and concurrent carboplatin and paclitaxel in patients with unresectable stage IIIA/B non-small cell lung cancer. METHODS: Patients received 2 cycles of induction carboplatin (area under the curve of 6) and paclitaxel (225 mg/m) on days 1, and 22. On day 43 concurrent TCRT and weekly x6 of carboplatin (area under the curve = 2) and paclitaxel (45 mg/m) was initiated. The TCRT dose was escalated from 60 to 74 Gy in 4 cohorts (60, 66, 70, and 74 Gy), and the 74 Gy cohort was expanded into a phase II trial. RESULTS: Sixty-two patients were enrolled; the median age 57 years (range, 36-82), 39 were male (63%), 61 (98%) had a performance status of 0 or 1, 28 (45%) had stage IIIA disease, 21 (34%) had >5% weight loss, and the median forced expiratory volume 1 = 2.10 liters (range, 1.02-3.75). With a median follow-up for survivors of approximately 9 years (range, 7-11 years) the median progression-free survival, time to tumor progression, and overall survival (OS) (with 95% confidence intervals) were 10 (8.5-17), 15 (9-50), and 25 months (18-37), respectively. The 5-year progression-free survival and OS rates were 21% (12-32%) and 27% (17-39%), respectively. The 10-year OS rate was 14% (7-25%). CONCLUSION: The long term survival rate compares favorably to other treatment approaches for stage III non-small cell lung cancer

A Phase 2 Study of Bortezomib in Relapsed, Refractory Myeloma

BACKGROUND Bortezomib, a boronic acid dipeptide, is a novel proteasome inhibitor that has been shown in preclinical and phase 1 studies to have antimyeloma activity. METHODS In this multicenter, open-label, nonrandomized, phase 2 trial, we enrolled 202 patients with relapsed myeloma that was refractory to the therapy they had received most recently. Patients received 1.3 mg of bortezomib per square meter of body-surface area twice weekly for 2 weeks, followed by 1 week without treatment, for up to eight cycles (24 weeks). In patients with a suboptimal response, oral dexamethasone (20 mg daily, on the day of and the day after bortezomib administration) was added to the regimen. The response was evaluated according to the criteria ofthe European Group for Blood and Marrow Transplantation and confirmed by an independent review committee. RESULTS Of 193 patients who could be evaluated, 92 percent had been treated with three or more ofthe major classes of agents for myeloma, and in 91 percent, the myeloma was refractory to the therapy received most recently. The rate of response to bortezomib was 35 percent, and those with a response included 7 patients in whom myeloma protein became undetectable and 12 in whom myeloma protein was detectable only by immuno-fixation. The median overall survival was 16 months, with a median duration of response of 12 months. Grade 3 adverse events included thrombocytopenia (in 28 percent of patients), fatigue (in 12 percent), peripheral neuropathy (in 12 percent), and neutropenia (in 11 percent). Grade 4 events occurred in 14 percent of patients. CONCLUSIONS Bortezomib, a member of a new class of anticancer drugs, is active in patients with relapsed multiple myeloma that is refractory to conventional chemotherapy

Peterborough Cathedral Nave Ceiling Conservation Project

The nave ceiling of Peterborough Cathedral is of international significance. Canted and constructed of wooden boards, it was erected and painted in the first half of the 13th century; it was subject to major repair and repainting twice, once in the 1740s and once in the 1830s. It had been much written about but had had very little research carried out on its physical structure, prior to this project. Concerns about the condition of the nave ceiling in the early 1990s made its conservation a priority, and in 1994 a major conservation programme was proposed, led by the cathedral architect Julian Limentani. Given the international status of the ceiling, the project was conceived from the first as a collaborative effort and, also from the first, there was an intention that the intellectual results of the project should be published. A team of experts was put together drawing on the expertise of the Cathedral's own staff, English Heritage (now Historic England), the Courtauld Institute of Art and the Cathedrals Fabric Commission for England (CFCE). They included paint and wood conservators, art historians and archaeologists, dendrochronologists and environmental specialists. Emergency Works begun in August 1997 by a combined team from The Perry Lithgow Partnership and Hugh Harrison Conservation provided the opportunity to establish the best methods for dealing with the flaking paint, and cleaning and conserving the structure as a whole.Four main phases of work then followed between 1998 and 2001 before a fire in the Cathedral in November 2001 proved a setback to the conservation programme. The final phase of work was postponed until 2003 while the damage caused by the fire was assessed, with cleaning throughout the Cathedral, prompting study and tree-ring dating of the other medieval ceilings in the building. Throughout the conservation programme, as well as the conservation itself, every effort was made to record the discoveries of the conservators, aided by a programme of photogrammetry and photomontage of the ceiling. Additional to the conservation work, but crucial to a proper understanding of the structures, tree-ring dating was undertaken on both the remnant of medieval roof and on the ceiling itself. The transept ceilings proved to be of particular importance, since they proved to be the chronological and design forerunners to the nave ceiling. Both the pre- and post-fire works generated numerous technical reports, on the structure and its physical history, on the paint of different periods, on the condition and treatment of the roof, ceiling and painted decoration, on the dendrochronology and on the methods of survey and documentation