Malika Siker

Enhanced methods for assessment of the trace element composition of Iron Age bone

Modern, ultra-trace, analytical methods, coupled with magnetic sector ICP-MS (HR-ICP-MS), were applied to the determination of a large suite of major and trace elements in Iron Age bones. The high sensitivity and un-paralleled signal-to-noise characteristics of HR-ICP-MS enabled the accurate measurement of Ag, Al, As, Ba, Ca, Cd, Ce, Co, Cr, Cu, Fe, La, Li, Mg, Mn, Ni, P, Pb, Pt, Rb, Sr, U, V, and Zn in small bone sections (<75 mg). Critically, the HR-ICP-MS effectively addressed molecular interferences, which would likely have compromised data generated with quadrupole-based ICP-MS instruments. Contamination and diagenetic alteration of ancient bone are grave concerns, which if not properly addressed, may result in serious misinterpretation of data from bone archives. Analytical procedures and several chemical and statistical methods (Principal Components Analysis - PCA) were studied to assess their utility in identifying and correcting bone contamination and diagenetic alteration. Uncertainties in bone (femur) sampling were characterized for each element and longitudinal variation was found to be the dominant source of sampling variability. However the longitudinal variation in most trace elements levels was relatively modest, ranging between 9 and 17% RSD. Bone surface contamination was evaluated using sequential acid leaching. Calcium-normalized metal levels in brief, timed, dilute nitric acid leaches were compared with similarly normalized interior core metal levels to assess the degree of surface enrichment. A select group of metals (Mn, Co, Ni, Ag, Cd, and Pt) were observed to be enriched by up to a factor of 10 in the bone surface, indicating that that these elements may have a higher contamination component. However, the results of sequential acid leaching experiments indicated that the single acid leaching step was effective in removing most surface-enriched contaminants. While the leaching protocol was effective in removing contaminants associated with the bone surface, there remained potentially significant residual levels of soil-sourced contaminant tracers within the leached bone. To address this issue a mathematical procedure, based on metal/aluminum ratios, was developed to correct-for the soil-contaminant metal pools. Soil correction fractions for the primary anthropogenically mobilized metals evaluated were greatest for Pb (13.6%) followed by As (4.4%), Ag (3.9%), and Cd (0.94%). Although median soil corrections were typically low, many samples did require a much larger correction, thus both bone cleaning and soil corrections may be necessary to realize accurate endogenous bone elemental data. The results of the PCA analysis were remarkably consistent with outcomes from the chemical and elemental ratio protocols evaluated in the study, and suggest that loadings on certain factors will be helpful in screening for soil-biased samples and in identifying diagenetically altered bone. Application of these contamination evaluation and correction tools was made possible by the high-quality, multi-element, datasets produced by HR-ICP-MS. Large variations in bone core concentrations between the 80 Iron Age specimens examined were observed for all the primary trace elements and in many of the supporting elements, even after correction for major contaminant components.

Resection versus radiosurgery for patients with brain metastases

Brain metastases occur in 20-40% of adult cancer patients and the incidence is apparently increasing. Despite advances in treatment, the prognosis of these patients is poor, with a median survival of approximately 4 months. Whole brain radiation therapy is the standard of care for most patients with brain metastases. Randomized trials have demonstrated that focal treatments, such as resection and radiosurgery, yield significant improvement in the survival of patients with a single metastasis. The utility of these strategies, specifically in terms of increased survival, is unclear in patients with more than one metastasis. In addition to focal treatments, future directions in the treatment of brain metastases include the development of intraoperative imaging capabilities, improved methods of identifying patients who are likely to benefit from treatment, systemic agents, such as chemotherapy and radiosensitizers, and the incorporation of targeted and antiangiogenic therapies.

Role of Radiation Therapy in Cutaneous Melanoma

Cutaneous melanoma is a disease that often has an aggressive and unpredictable course. It was historically thought to be a radioresistant neoplasm; however, substantial radiobiologic and clinical evidence has emerged to refute this notion. Improved local control has been demonstrated with the use of adjuvant radiation therapy delivered to the primary site or regional lymphatics in patients with high-risk clinical or pathologic features. Despite improved local control, high-risk cutaneous melanoma often spreads systemically, leading to poor survival. In the setting of systemic progression, radiation therapy can frequently palliate symptomatic sites of metastatic disease.

Semicontinuous Low-Dose-Rate Teletherapy for the Treatment of Recurrent Glial Brain Tumors: Final Report of a Phase I/II Study

PURPOSE Semicontinuous low-dose-rate teletherapy (SLDR) is a novel irradiation strategy that exploits the increased radiosensitivity of glial cells in a narrow range of reduced dose rate. We present the final report of a prospective Phase I/II study testing the feasibility of SLDR for the treatment of recurrent gliomas. METHODS AND MATERIALS Patients with previously irradiated recurrent gliomas were enrolled from November 1993 to March 1998. Patients received SLDR, delivered 6 to 8 hours/day at a dose rate of 40 to 50 cGy/hour for a total dose of 30 to 35 Gy given over 12 days using a modified cobalt-60 treatment unit. Acute central nervous system toxicity after SLDR treatment was the primary endpoint. Overall survival was a secondary endpoint. RESULTS Twenty patients were enrolled (14 World Health Organization Grade 4 glioma, 5 Grade 2 glioma, 1 ependymoma). No patients developed ≥ Grade 3 central nervous system toxicity at 3 months without radiographic evidence of tumor progression. Overall survival after SLDR was 56% at 6 months, 28% at 12 months, and 17% at 24 months. One patient survived >48 months, and 1 patient survived >60 months after SLDR treatment. Re-resection before SLDR treatment significantly improved 1-year overall survival for all patients and patients with Grade 4 glioma. CONCLUSION The delivery of SLDR is feasible in patients with recurrent gliomas and resulted in improved outcomes for patients who underwent re-resection. There were 2 long-term survivors (>48 months). This pilot study supports the notion that reduced dose rate influences the efficacy and tolerance of reirradiation in the treatment of recurrent gliomas.

Radiation for brain metastases.

The use of radiotherapy in the treatment of brain metastases includes whole brain radiotherapy (WBRT), either as definitive or as adjuvant treatment following resection or radiosurgery, radiosurgery alone, and brachytherapy. WBRT has been the primary treatment for brain metastases for over 50 years, improving local control and survival as well as providing effective palliation. While definitive WBRT remains the standard of care for most patients, adjuvant WBRT with radiosurgery and surgical resection has been shown to improve local control and survival in a subset of patients [1–3].

Local Disease Control in Ocular Adnexal Lymphoproliferative Disorders: Comparative Outcomes of MALT Versus Non-MALT Histologies

Micro‐Abstract The efficacy of involved field radiotherapy (IFRT) in the outcomes of patients with different subtypes of ocular adnexal lymphoproliferative disorder is lacking. We retrospectively analyzed and compared the outcomes of patients with mucosa‐associated lymphoid tissue (MALT) and non‐MALT ocular adnexal lymphoproliferative disorder after being treated with IFRT. Our results reveal that IFRT provided excellent disease control with superior failure‐free survival in the MALT cohort when compared with the non‐MALT cohort. Introduction: Ocular adnexal lymphoproliferative disorders (OALDs) are almost exclusively of B‐cell origin, with the majority being extra‐nodal marginal zone lymphomas of mucosa‐associated lymphoid tissue (MALT). The comparative efficacy of involved field radiation therapy (IFRT) in MALT vs. non‐MALT OALDs is not known. Materials and Methods: We present a single‐center, large cohort, retrospective study of the efficacy of IFRT in OALDs. Failure‐free survival (FFS), complete remission, and local, regional, and distant failure were determined for 112 patients with MALT OALDs (n = 71) and non‐MALT OALDs (n = 41) cohorts. Results: Fifty‐six patients with MALT OALD and 26 patients with non‐MALT OALD received IFRT only (without any planned concurrent or sequential systemic chemothereapy or chemo‐immunotherapies). Among the OALD cohorts treated with only IFRT, complete remission was achieved in 49 (87.5%) patients in the MALT cohort and 23 (88.4%) in the non‐MALT cohort (P = .99). Clinically, resolution of symptoms occurred in 83.3% and 93.3% of the patients in the MALT and non‐MALT cohorts, respectively. Local failure occurred in 4 (7.1%) patients in the MALT cohort, compared with 4 (15.3%) patients in the non‐MALT cohort (P = .24). Regional failure (or extra‐orbital failure) occurred in 5 (8.9%) patients in the MALT cohort and in 3 (11.5%) patients in the non‐MALT cohort (P = .71). Distant failure was reported in 1 (1.7%) and 2 patients (7.6%) in the MALT and non‐MALT cohorts, respectively (P = .18). The median follow‐up of survivors was 5.1 years (range, 0.1‐22.5 years) in the MALT cohort and 3.9 years (range, 0.1‐22.9 years) in the non‐MALT cohort. The 5‐year and 10‐year FFS was 95% (95% confidence interval [CI], 88%‐100%) and 83% (95% CI, 70%‐98%) for the ocular MALT and 67% (95% CI, 48%‐94%) and 56% (95% CI, 34%‐91%) for the non‐MALT cohorts, respectively (log rank for P = .025). On multivariate analyses, age (hazard ratio [HR], 1.06; 95% CI, 1.10‐1.12; P = .03), presence of non‐MALT histology (HR, 13.9; 95% CI, 2.05‐94.4; P = .007), and radiation dose < 30.6 Gy (HR, 5.27; 95% CI, 1.14‐24.3; P = .03) were associated with worse FFS. The 5‐year and 10‐year overall survival was 92% (95%, CI 83%‐100%) and 80% (95% CI, 66%‐96%) for the MALT and 78% (95% CI, 61%‐100%) and 62% (95% CI, 38%‐100%) for the non‐MALT cohorts, respectively (P = .80). Conclusion: Our results reveal that IFRT provided excellent disease control with superior FFS in the MALT cohort when compared with the non‐MALT group.

Comparing the quality of passively-scattered proton and photon tomotherapy plans for brain and head and neck disease sites

We compare the quality of photon IMRT (helical tomotherapy) with classic proton plans for brain, head and neck tumors, in terms of target dose uniformity and conformity along with organ-at-risk (OAR) sparing. Plans were created for twelve target volumes among eight cases. All patients were originally planned and treated using helical tomotherapy. Proton plans were generated using a passively-scattered beam model with a maximum range of 32 g cm(-2) (225 MeV), range modulation in 0.5 g cm(-2) increments and range compensators with 4.8 mm milling tool diameters. All proton plans were limited to two to four beams. Plan quality was compared using uniformity index (UI), conformation number (CN) and a EUD-based plan quality index (fEUD). For 11 of the 12 targets, UI was improved for the proton plan; on average, UI was 1.05 for protons versus 1.08 for tomotherapy. For 7 of the 12 targets, the tomotherapy plan exhibited more favorable CN. For proximal OARs, the improved dose conformity to the target volume from tomotherapy led to a lower maximum dose. For distal OARs, the maximum dose was much lower for proton plans. For 6 of the 8 cases, near-total avoidance for distal OARs provided by protons leads to improved fEUD. However, if distal OARs are excluded in the fEUD calculation, the proton plans exhibit better fEUD in only 3 of the 8 cases. The distal OAR sparing and target dose uniformity are generally better with passive-scatter proton planning than with photon tomotherapy; proton therapy may be preferred if the clinician deems those attributes critical. However, tomotherapy may serve equally as well as protons for cases where superior target dose conformity from tomotherapy leads to plan quality nearly identical to or better than protons and for cases where distal OAR sparing is not concerning.