Mantle Field Research Articles

Treatment of Mantle and Inverted Y Fields in Modern Era: A VMAT Approach.

Hodgkin's lymphoma has been treated with combined modality therapy (chemotherapy and radiation) with a very high degree of success. Total Nodal Irradiation (TNI) performed with large AP/PA mantle fields for treatment of axillary, cervical, and mediastinal lymphatics, provide adequate coverage to the mediastinum and bilateral axillae and hila, while blocking lungs. The para-aortic and pelvic lymph nodes are treated with the so called inverted-Y AP/PA fields, which often includes the spleen in cases of TNI. Multileaf Collimators (MLC) have been tried, but due to the irregular shape of the fields and necessity of island blocking in 3D treatment, they have not been successful in full elimination of Cerrobend blocks. We hypothesize that using two or three matched Volumetric Modulated Arc Therapy (VMAT) fields will not only eliminate a need for Cerrobend blocks or island blocks, but will also provide better target coverage and better organs at risk (OAR) sparing. Under IRB study, 10 patients were retrospectively planned using two or three matched VMAT technique for mantle and inverted-Y treatments of TNI that had been previously treated using MLC and Cerrobend block combination. Pinnacle treatment planning system version 16.2.1 was used to generate plans using mantle/inverted-Y technique and corresponding VMAT plans using 2-3 arcs per isocenter (2 isocenters per plan). Optimization was performed to cover targets with the prescribed dose of 1500 cGy in 10 fractions per institutional protocol. The VMAT plans were compared with traditional 3D plans. VMAT consistently provided better or similar results to traditional field arrangements. Target coverage: V15Gy - 95.45% vs 77.99% (p = 0.00017), OAR coverage: total lung V5Gy 63.7% vs 68.8% (p = 0.016), bone marrow mean dose 539.1 cGy vs 727.8 cGy (p = 0.00047), Integral Dose 464.1 mJ vs 573.9 mJ (p = 0.0026). Low isodose lines- mean volume of 5 Gy isodose line was not significantly different - 24036 cc vs 25091 cc (p = 0.271). Cord maximum dose was 40% lower for VMAT plans (p = 0.00006). Mean bladder dose was similar in VMAT plans compared to 3D plan - 821.7 cGy vs 804.9 cGy (p = 0.454). One counter-intuitive result is that the mean integral dose for 10 patients was 24% lower for VMAT plans. VMAT based mantle fields for TNI eliminates Cerrobend blocks and improve dosimetry significantly for target volumes and all OARs; including bone marrow, which plays important role in patient's recovery after chemotherapy, radiation and often stem cell transplantation in recurrent disease. Lower integral dose for VMAT plans is explained by the large irradiated in-fields and small out-of-field volumes. The VMAT process requires minimal effort for optimization and is economical compared to the traditional planning, while improving the target coverage and decreasing dose to OARs.

Isotopic Composition for Helium in Late Cenozoic South-Baikal and South-Khangai Volcanic Areas

The paper considers isotopic composition of helium (3Не/4Не = R) in groundwater of South-Baikal (SBVA) and South-Khangai volcanic areas (SKhVA) during the Late Cenozoic period. The differences in the behavior and magnitude of the parameters were established. It is found that the mentioned differences in 3Не/4Не concentrations within South-Baikal and South-Khangai volcanic areas correspond to mantle reservoirs with different helium isotope compositions. This confirms that the Late Cenozoic volcanism of South-Baikal and South-Khangai volcanic area is controlled by mantle sources related to mantle plumes of the Central-Asian hot mantle field.

T064: Doxorubicin exposure and breast cancer risk in adolescent and adult Hodgkin lymphoma survivors

Figure 1: Doxorubicin dose-response plot. Dose-response curve for continuous doxorubicin dose and breast cancer risk, adjusted for age at HL treatment, chest radiotherapy and gonadotoxic treatment. Adjusted HRs for doxorubicin dose categories are added. Background: Female Hodgkin lymphoma (HL) survivors treated with chest radiotherapy at a young age have a strongly increased risk of breast cancer (BC). Recent studies in childhood cancer survivors have shown that doxorubicin may also increase BC risk. So far, the association between doxorubicin and BC risk has not been examined in cancer survivors treated at adolescent/adult ages. Methods: We assessed BC risk in a cohort of 1964 female five year HL survivors, treated at ages 15–50 years in 20 Dutch hospitals between 1975 and 2008. Cumulative BC incidence was estimated in the presence of death as a competing risk. Treatment factors were time-dependently included in the multivariable Cox regression analysis, focusing on the effect of doxorubicin exposure on BC risk. Results: HL survivors were treated at a median age of 27.8 years (interquartile range (IQR) 21.9–35.2 years). After a median follow-up of 18.3 years (IQR 12.9–24.7) years, 200 women had developed invasive BC (n=190) and/or ductal carcinoma in situ (n=49). The 30-year cumulative incidence was 19.4% (95% confidence Interval (CI) 16.6–22.3%). Among patients treated with chemotherapy (n=1113), receipt of doxorubicin-containing chemotherapy increased from 32.6% in 1975–1986 to 84.5% in 1998–2008. In multivariable analysis a cumulative dose of >200 mg/m2 was associated with increased BC risk (HR 1.7; 95% CI 1.1–2.4), compared to patients not treated with doxorubicin. BC risk increased 19% (HR 1.19; 95% CI 1.1–1.3) per additional 100 mg/m2 doxorubicine (ptrend=0.003). Receipt of mantle or axillary field irradiation or gonadotoxic therapy did not modify the association between doxorubicin and BC risk. Among patients who received >200 mg/m2 doxorubicin, the HR was 1.6 (95% CI 1.1–2.5) for patients treated with and 2.0 (95% CI 0.9–4.2) for patients treated without mantle or axillary field irradiation (Pinteraction=0.35). Gonadotoxic treatment (>8.4 g/m2 procarbazine or pelvic irradiation) significantly decreased the risk of BC. Conclusion: This study shows that doxorubicin is associated with an increased BC risk among adolescent and adult HL survivors. Now that radiotherapy doses and volumes have decreased and doxorubicin increasingly forms the backbone of HL treatment, the potential association of doxorubicin with increased BC risk is an important issue.

Diagrammatic Approach to Delineate Phrenic Nerve in Central Lung Tumors

Incremental use of high-dose radiation therapy (RT) with SABR in thoracic tumors has led to identification of many unusual toxicities (chest wall pain, rib fractures, vascular perforation, brachial plexopathy) and consequently additional organs at risk (OARs; chest wall, ribs, bronchial wall, carotid artery, brachial plexus). Phrenic nerve is another structure that may be affected at any point during its long course from origin until end, although symptomatic toxicities have been reported rarely in the setting of reirradiation, large-volume irradiation such as mantle field, or SABR. We undertook a prospective study to describe the delineation of phrenic nerve course on RT planning computed tomography scan as an OAR. An anonymized RT planning computed tomography scan of neck and thorax (1.5-mm slice thickness, intravenous contrast) was used for the study. Radiology textbooks and publications were reviewed, and the course was delineated with the help of 2 radiologists and 6 radiation oncologists well versed with thoracic radiologic anatomy. A step-by-step description in the form of a pictorial essay is given. The adjacent structures including cervical vertebrae, cervical and mediastinal vessels, lungs, heart, and so on were identified, and the course of phrenic nerve on either side is described in relation to these structures. Delineation of the phrenic nerve as an OAR is challenging but feasible. We recommend routine delineation of the phrenic nerve as an OAR during thoracic RT. Although specific dose constraints are not known yet, unnecessary dose to the same during RT planning should be minimized.

Cambrian rift magmatism recorded in subvolcanic sills of the Ediacaran-Cambrian La Ciénega Formation, NW Mexico

Mafic-ultramafic subvolcanic metabasalt sills intrude Ediacaran and Cambrian strata of the La Ciénega Formation of Sonora, Mexico. Sills are typically 1–7.5 m thick, with minor associated thin (∼10 cm thick) intrusions. Sills are typically bed parallel with upper and/or lower tempered (quenched) borders and porphyritic textures characterized by abundant olivine and pyroxene pseudomorphs that have been transformed to clay and carbonate minerals. Metamorphic halos in adjacent dolostones and quartzites occur at the bottom and top contacts, and metabasalt sills contain carbonate veins typical of hydrothermal alteration and mobilization. Unlike surface flows of the overlying Cerro Rajón Formation, all sills in the La Ciénega Formation lack evidence of crystal settling, yet evidence for assimilation of country rocks is present. Assimilation is more typical of sills rather than flows and is diagnostic of sills in the El Arpa Formation, a stratigraphically lower unit in the succession. Actinolite-chlorite-albite metamorphic mineral paragenesis suggests low-grade greenschist facies metamorphism for these metabasaltic rocks. Although their primary mineralogy is obscured due to alteration, olivine and clinopyroxene pseudomorphs are present and their major and trace element geochemistry suggest they were derived from alkaline basaltic magmas with low (normalized) SiO2N (22.7–43.1 wt%), high MgON (7.25–16.6 wt%), and high TiO2N (4.04–6.27 wt%). Immobile trace elements suggest these sills were originally alkaline rift-related basalts with OIB-type signatures. Tectonic discrimination diagrams suggest continental rift magmatism with low geochemical evolution ratios and relatively low mantle melting rates when compared to contemporaneous rift related magmatism. Sr-Hf-Nd-Pb isotopes suggest the metabasalts originated from an Enriched Mantle I (EMI) reservoir and melting occurred during adiabatic decompression. These geochemical characteristics are remarkably similar to volcanic rocks of the Cerro Rajón Formation. The inferred magmatic composition, mantle melting rates, petrography and field relations of the La Ciénega Formation metabasalt are consistent with a low viscosity feeder system like that envisaged to have sourced volcanic rocks of the overlying Cambrian (Terreneuvian) Cerro Rajón Formation. Together, evidence from these two volcanic units is consistent with a Cambrian continental rift event close to the onset of the Sauk transgression.

Combined skin-sparing mastectomy and immediate implant-based breast reconstruction: Outcome following mantle field irradiation versus outcome following whole-breast irradiation

Mastectomy may be needed in the context of previous radiotherapy in cases of breast carcinoma following mantle field radiotherapy for Hodgkin lymphoma or in cases of local relapse or second primary tumours after breast conserving therapy including whole-breast irradiation (BCT). The outcome of combined skin-sparing mastectomy and immediate implant-based breast reconstruction (SSM-IIBR) has been reported to be unfavourable in these cases. To compare the outcome of SSM-IIBR after mantle field radiotherapy to that after BCT and to compare both to the outcome observed in non-irradiated breasts. The prevalences of short-term events, device loss, long-term corrections and secondary reconstructions, and reversion to autologous tissue techniques of 42 SSM-IIBRs performed after mantle field irradiation were compared to those of 47 salvage SSM-IIBRs following BCT. Both outcomes were compared to the outcome in the contralateral, non-irradiated breast of the subgroup of 23 women in the BCT group. The groups were comparable in terms of patient- and procedure-related risk factors, except for time lapse after previous therapy, intraoperative device weight, and the fraction of immediate use of a definitive implant. The outcome of SSM-IIBR after mantle field irradiation significantly differs favourably from that after BCT. It matches the outcome observed in non-irradiated breasts. Skin-sparing mastectomy combined with immediate implant-based breast reconstruction is a fully justifiable option for women who previously underwent mantle field irradiation for Hodgkin lymphoma. We feel that the unfavourable outcome observed in women who previously underwent BCT necessitates an alternative reconstructive modality.

Elevated resting heart rate is a marker of subclinical left ventricular dysfunction in hodgkin lymphoma survivors.

BackgroundThoracic irradiation is one of the cornerstones of Hodgkin lymphoma (HL) treatment, which contributes to high rates of long-term survivorship, but begets a life-long increased risk of heart disease including heart failure. At the cardio-oncology (CO) clinic, persistent sinus tachycardia or elevated resting heart rate (RHR) is frequently observed in these patients. The aim of this study was to evaluate the relation between RHR and left ventricular (LV) dysfunction.MethodsIn 75 HL survivors visiting our CO-clinic echocardiographic evaluation of LV systolic and diastolic function including global longitudinal strain (GLS) was performed to assess subclinical LV dysfunction.ResultsMedian age of HL diagnosis was 24 [25th-75th percentile: [19], [29]] years with a 17 [12], [25] year interval to CO-clinic visit and 31 patients (41%) were male. Average RHR was 78 ± 14 bpm and 40% of patients (N = 30) had an elevated RHR defined as ≥ 80 bpm. While there was no difference in LV ejection fraction (55.6 ± 4.3 vs. 54.8 ± 6.6; p = 0.543), patients with elevated RHR had abnormal GLS (-15.9% vs. −18.3%, p = 0.045) and higher prevalence of diastolic dysfunction (73.3% vs. 46.7%; p = 0.022). GLS, E/e’ ratio and presence of diastolic dysfunction were independently associated with RHR when correcting for age, sex and mantle field irradiation. A significant improvement was observed of the RHR-association model with solely extracardiac confounders when LV-function parameters were added to the model (F-statistic = 6.36, p = 0.003).ConclusionsThis study indicates RHR as a possible marker for subclinical LV-dysfunction in HL survivors.

Development and Validation of a Breast Cancer Risk Prediction Model for Childhood Cancer Survivors Treated With Chest Radiation: A Report From the Childhood Cancer Survivor Study and the Dutch Hodgkin Late Effects and LATER Cohorts.

Women treated with chest radiation for childhood cancer have one of the highest risks of breast cancer. Models producing personalized breast cancer risk estimates applicable to this population do not exist. We sought to develop and validate a breast cancer risk prediction model for childhood cancer survivors treated with chest radiation incorporating treatment-related factors, family history, and reproductive factors. Analyses were based on multinational cohorts of female 5-year survivors of cancer diagnosed younger than age 21 years and treated with chest radiation. Model derivation was based on 1,120 participants in the Childhood Cancer Survivor Study diagnosed between 1970 and 1986, with median attained age 42 years (range 20-64) and 242 with breast cancer. Model validation included 1,027 participants from three cohorts, with median age 32 years (range 20-66) and 105 with breast cancer. The model included current age, chest radiation field, whether chest radiation was delivered within 1 year of menarche, anthracycline exposure, age at menopause, and history of a first-degree relative with breast cancer. Ten-year risk estimates ranged from 2% to 23% for 30-year-old women (area under the curve, 0.63; 95% CI, 0.50 to 0.73) and from 5% to 34% for 40-year-old women (area under the curve, 0.67; 95% CI, 0.54 to 0.84). The highest risks were among premenopausal women older than age 40 years treated with mantle field radiation within a year of menarche who had a first-degree relative with breast cancer. It showed good calibration with an expected-to-observed ratio of the number of breast cancers of 0.92 (95% CI, 0.74 to 1.16). Breast cancer risk varies among childhood cancer survivors treated with chest radiation. Accurate risk prediction may aid in refining surveillance, counseling, and preventive strategies in this population.

Anthracycline exposure and breast cancer risk in female Hodgkin lymphoma survivors.

12074 Background: Female Hodgkin lymphoma (HL) survivors treated with chest radiotherapy (RT) at a young age have a strongly increased risk of breast cancer (BC). Recently concern has been raised that anthracyclines may also increase BC risk, based on studies in childhood cancer survivors with/without a history of chest RT. So far, the association between anthracyclines and BC risk has not been examined in cancer survivors treated at adolescent/adult ages. Now that RT dose and volumes are decreasing, the potential contribution of anthracyclines to BC risk is an important issue. Methods: We assessed BC risk in a cohort of 2314 female 5-year HL survivors, treated at ages 15-50 years and diagnosed between 1965 and 2008 in 20 Dutch hospitals. Treatment factors were time-dependently included in the analysis, focusing on the effect of anthracycline exposure on BC risk. Results: After a median follow-up of 18.8 years, 258 women developed invasive BC or ductal carcinoma in situ as a subsequent malignancy. The 30-year cumulative incidence was 15.0% (95% Confidence Interval (CI) 12.8-17.4%). Mantle field RT (or other RT involving both axillae) was associated with increased risk of BC (Hazard ratio (HR) 1.9; 95% CI 1.2-2.8) compared to no supradiaphragmatic RT or RT to the neck only (Table 1). Gonadotoxic treatment (>4.2 g/m2 procarbazine or pelvic RT) significantly decreased this risk. In a multivariable analysis, anthracycline exposure was associated with increased BC risk (HR 1.8; 95% CI 1.3-2.5) in patients who received a cumulative dose of >200 mg/m2. Among patients exposed to gonadotoxic treatment, the HR of BC associated with >200mg/m2 anthracyclines was 3.8 (95% CI 2.0-7.2), with a trend for higher risk with higher anthracycline dose (HR 1.58 per 100mg/m2 anthracycline, p<0.001). Conclusions: Our results suggest an association of anthracyclines with BC risk in HL survivors. Also when accounting for the protective effect of gonadotoxic treatment on RT-associated BC risk, anthracyclines significantly contributed to a higher BC risk.[Table: see text]

Anaplastic Thyroid Cancer Presenting With Brain Metastasis: 17-year Progression Free Survival

Anaplastic Thyroid Cancer is the most aggressive thyroid cancer with a median survival of just five months. Long term survival has been reported in locally aggressive cases but has yet to be reported in metastatic disease. This is a report of a 34-year-old male who presented with symptoms of dizziness, confusion, intermittent headaches, and erratic behavior for two weeks found to have metastatic anaplastic thyroid cancer. CT of the head revealed a 1 cm ring enhancing lesion and he was taken to the operating room for a left parietal craniotomy with mass removal. Initial pathology suggested papillary thyroid origin. His neck exam revealed a palpable 3 cm mass in the right thyroid lobe and he subsequently underwent total thyroidectomy. Final pathology revealed anaplastic carcinoma identical to the brain lesion. Post-operatively, he underwent 15 cycles of whole brain radiation therapy. Two additional brain lesions were identified after thyroidectomy and a third was identified after whole brain radiation. He underwent stereotactic radiosurgery of these three lesions less than two months after thyroidectomy. The patient went on to receive modified mantle field irradiation to the neck, thyroid bed, and the upper mediastinum and chemotherapy with doxorubicin for 6-8 weeks and temozolomide for 2 years. Radioactive iodine treatment was not administered. The patient has currently survived 17 years and his persistent, but stable, brain lesions are being followed with serial imaging. He remains clinically and neurologically asymptomatic. This is the first case presenting with long-term survival in a patient with metastatic anaplastic thyroid carcinoma.

Middle-aged woman with dropped head syndrome due to remote exposure to mantle field radiation

A 61-year-old woman presented to the office for evaluation of progressive neck muscle weakness over 10 years. She reported initial difficulty with an eventual inability to lift up her head...

The Devonian accretionary orogen of the North Patagonian cordillera

The Andean basement of NW Patagonia contains remnants of a Devonian accretionary orogen that lasted for about 50 Ma. We present and review U-Pb geochronology, major and trace element geochemistry and O- and Hf-isotope analyses of zircon for Devonian igneous and metasedimentary rocks from the western edge of the North Patagonian Massif to the Pacific coast. Two contrasting magmatic domains are characterised. The Foreland Devonian Domain (FDD) of the North Patagonian Massif is dominated by subduction-related calcalkaline granite, granodiorite and tonalite emplaced in the interval c. 405–395 Ma and here named the San Martín arc. They are generally enriched in alkalis, light rare earth and Large Ion Lithophile elements, and have igneous zircon with δ18O mostly in the range +6 to +9‰ and ƐHft typically +3 to −5, indicating magmas that incorporated continental crustal material, possibly Mesoproterozoic. A younger (374 ± 3 Ma) body in this group has lower δ18O (down to +5‰) and Hf-isotope characteristics at the primitive end of this range. The Pacific Devonian Domain (PDD) lies on the western flank of the Andes and has uniformly primitive character. Granitic rocks here represent a more extended magmatic history (c. 395–355 Ma) and are mostly subalkaline tonalites with δ18O (<+6‰) that fall within or below the normal mantle field: with one exception their ɛHft values are > +4 and closer to Devonian depleted mantle composition. The PDD also has metabasalts of both N-MORB and E-MORB affinities, interbedded with Devonian turbidite metasandstones in which detrital zircon O- and Hf-isotope compositions and morphology indicate coetaneous derivation from the FDD arc. The results lead to a tectonic model involving continental arc, forearc rifting, Chaitenia oceanic arc and marginal basin formation, double arc subduction, and marginal basin closure in Mississippian times. This is recognisable as part of a more extensive Devonian accretion scenario along the SW Gondwana margin.

High risk of cardiovascular side effects after treatment of Hodgkin's lymphoma - is there a need for intervention in long-term survivors?

BackgroundHodgkin lymphoma (HL) patients have a good prognosis after adequate treatment. Previous treatment with mantle field irradiation has been accompanied by an increased long-term risk of cardiovascular disease (CVD). This study identified co-morbidity factors for the development of cardiovascular side effects and initiated an intervention study aimed to decrease morbidity and mortality of CVD in HL survivors.DesignHodgkin lymphoma patients aged ≤45 years diagnosed between 1965 and 1995 were invited to participate. In total, 453 patients completed a questionnaire that addressed co-morbidity factors and clinical symptoms. Of these, 319 accepted to participate in a structured clinical visit. The statistical analyses compared individuals with CVD with those with no CVD.ResultsCardiovascular disease was reported by 27.9%. Radiotherapy (odds ratio [OR]: 3.27), hypertension and hypercholesterolemia were shown to be independent risk factors for the development of CVD. The OR for CVD and valve disease in patients who received radiotherapy towards mediastinum was 4.48 and 6.07, respectively. At clinical visits, 42% of the patients were referred for further investigation and 24% of these had a cardiac ultrasound performed due to previously unknown heart murmurs.ConclusionRadiotherapy towards mediastinum was an independent risk factor for CVD as well as hypercholesterolemia and hypertension. A reasonable approach as intervention for this cohort of patients is regular monitoring of hypertension and hypercholesterolemia and referral to adequate investigation when cardiac symptoms appear. Broad knowledge about the side effects from radiotherapy in the medical community and well-structured information regarding late side effects to the patients are all reasonable approaches as late effects can occur even 40 years after cancer treatment.

Investigation Of Petrological Characteristics Of The Upper Mantle In Hadji-Abad Ophiolitic Complex (South Of Iran): Based On Mineral Chemistry

The mantle peridotites of the Hadji-Abad ultramafic complex in Hormozgan province, show some petrological evolutions of the upper mantle of southern Iran. The complex includes harzburgite, lherzolite, dunite and chromitite. Evidences such as different generations of minerals, lobate boundaries between grains, elongation of cr-spinels and pyroxenes, incongruent melting related textures and exsolution lamellae of clinopyroxene in orthopyroxene show that the rocks in this complex first underwent high temperature-pressure in the upper mantle, and then emplaced in the crust. The chemical composition of chromites in the Hadji Abad dunites and chromitites is similar to that of boninite melts, while, the mineral chemistry of the harzburgitic and lherzolitic show that the host peridotites belong to the upper mantle and have been depleted from incompatible elements due to 15 to 20 percent partial melting. Geo-thermometric calculations reveal that the studied peridotites equilibriated in upper mantle and spinel-peridotite stability field. Using tectonomagmatic discrimination diagrams shows that the Hadji-Abad ultramafic complex is part of an oceanic lithosphere above suprasubduction zone which has undegone partial melting, high temperature deformations and mantle metasomatism processes associated with this environment. These evidences along with the geological and tectonic setting of the Hadji Abad complex adjacent to the Zagros thrust indicate that the complex probably was created in the mantle section under a back-arc basin and then tectonically emplaced as part of Esfandagheh-Hadji-Abad melange in the current situation during the upper Cretaceous. These informations confirm the dependence of the Esfandagheh-Hadji-Abad ophiolite melange on the Neotethyan oceanic lithosphere in southern Iran.

Fluid source and metal precipitation mechanism of sediment-hosted Chang'an orogenic gold deposit, SW China: Constraints from sulfide texture, trace element, S, Pb, and He-Ar isotopes and calcite C-O isotopes

AbstractThe source of fluids and their mechanism of metal precipitation in sediment-hosted, disseminated orogenic gold deposits are ambiguous. Pyrite texture, trace element, S, Pb, and He-Ar isotope compositions of sulfides and C-O isotope data of calcite from Chang'an orogenic gold deposit in the Ailaoshan orogenic belt, southwest (SW) China, were studied to provide a new genetic model for the sediment-hosted orogenic gold deposit, furthering knowledge of the source of fluids and their mechanism of metal precipitation. Orebodies at Chang'an are mainly hosted by Ordovician turbidite with a few in Oligocene syenite. Two stages of mineralization have been identified in the deposit: stage I disseminated quartz-arsenopyrite-pyrite and stage II veined quartz-calcite-polymetallic sulfides. Five generations of pyrite have been identified in turbidite: pre-ore syn-sedimentary pyrite, pyI-1, and pyI-2 in stage I, and pyII-1 and pyII-2 in stage II, and an unzoned pyrite population developed in syenite. PyI-1 commonly overgrows syn-sedimentary pyrite with irregular boundaries and contains arsenopyrite, galena, chalcopyrite, and electrum inclusions along the boundaries. PyI-1 is overgrown by thin and inclusion-free pyI-2, and crosscut by pyII-1, which is rimmed by pyII-2.The syn-sedimentary pyrite is distributed parallel to the sedimentary bedding and contains As (620.8 ppm), Pb (61.6 ppm), Ni (59.8 ppm), Mo (54.4 ppm), Co (23.4 ppm), and Cu (13.0 ppm) with low-Au content of 0.06 ppm. This pyrite has δ34S values of −18.1 to +30.4‰ and high-radiogenic Pb isotope ratios (average 206Pb/204Pb, 207Pb/204Pb, and 208Pb/204Pb of 19.05, 15.86, and 39.87, respectively). PyI-1 and coexisting arsenopyrite are enriched in invisible Au (up to 227.1 and 353.3 ppm, respectively), As, Ni, Cu, and Pb, while pyI-2 contain much lower trace element abundances relative to pyI-1 and arsenopyrite. Partial replacement of syn-sedimentary pyrite by pyI-1 plus arsenopyrite, galena, chalcopyrite, and electrum, and similar Pb isotope ratios between syn-sedimentary pyrite and pyI-1 indicate that reaction of external deep Au-rich fluids with syn-sedimentary pyrite is responsible for gold precipitation in stage I. PyI-1, arsenopyrite, and pyI-2 show a narrower δ34S range of −3.2 to 7.1‰ relative to syn-sedimentary pyrite, demonstrating that the fluid-pyrite interaction has homogenized the sulfur. The unzoned pyrite in syenite has similar mineral inclusions (arsenopyrite, galena, etc.), δ34S values (+0.6 to 6.3‰) and Pb isotope ratios to pyI-1, but much lower trace element abundances relative to pyI-1. It may be attributed to different reactions of similar fluids with different wall-rocks. PyII-1 and pyII-2 in stage II contain elevated As, Pb, Cu, Sb, Zn, and Ag with low mean Au content (3.3 ppm) and have δ34S ranges of −2.8 to +1.2‰ and −6.2 and −0.8‰, respectively. Galena in stage II has lower radiogenic Pb isotope ratios than stage I pyrites, indicative of a different Pb source or fluid evolution. The gases released from a mixture of pyII-1-pyII-2 have R/Ra of 0.38 to 0.98 and 40Ar*/4He of 0.50 to 1.34, falling between the fields of mantle-derived and crustal fluids. Late ore calcites have δ13CPDB of −8.7 to 2.7‰ and δ18OSMOW of 8.05 to 25.58‰, also plotting between sedimentary carbonate and mantle fields. These signatures indicate that ore fluids in stage II are base metal-rich fluids with a small amount of contribution from the mantle. Different ore assemblages, trace element composition and isotope data between stages I and II at Chang'an suggest that the deposit experienced an evolution from early Au-rich fluids to late base metal-rich ones. This study highlights that ore metals in sediment-hosted disseminated orogenic gold deposits may be sourced from both deep fluids and local wall-rock, and that fluid-rock interaction behaved as a key control on ore precipitation.

MON-446 Anaplastic Thyroid Cancer Presenting with Brain Metastasis: 17-Year Progression Free Survival

Background: Anaplastic Thyroid Cancer is the most aggressive thyroid cancer with a median survival of just five months. Long term survival has been reported in locally aggressive cases, but has yet to be reported in metastatic disease. Case Information: A 34-year-old male presented with symptoms of dizziness, confusion, intermittent headaches, and erratic behavior for two weeks. CT of the head revealed a 1 cm ring enhancing lesion in the left parietal lobe with surrounding vasogenic edema. He was taken to the operating room for a left parietal craniotomy and a vascular, solid mass was removed. Initial pathology suggested papillary thyroid origin due to positive staining for thyroid transcription factor (TTF) and thyroglobulin (Tg). On exam, he had a palpable 3 cm mass in the right thyroid lobe with no associated adenopathy. He underwent thyroidectomy to optimize post-operative radioactive iodine treatment. Intraoperative frozen section revealed anaplastic thyroid cancer and final pathology revealed anaplastic carcinoma identical to the brain lesion. The tumor pathology showed extension through the thyroid capsule with lymphovascular invasion and one of two positive lymph nodes. Post-operatively, he underwent 15 cycles of whole brain radiation therapy for a total of 35 Gy. Two additional brain lesions were identified after thyroidectomy and a third was identified after whole brain radiation. He underwent stereotactic radiosurgery of these three lesions less than two months after thyroidectomy. The patient went on to receive modified mantle field irradiation (46 cycles, total 55.2 Gy) to the neck, thyroid bed, and the upper mediastinum. Additionally, he received chemotherapy with doxorubicin 6-8 weeks and temozolomide for 2 years. Thyroid uptake studies showed minimal residual iodine-avid disease and, in the setting of chemotherapy-induced cytopenias, radioactive iodine treatment was not administered. The patient has currently survived 17 years post-treatment. His persistent, but stable, brain lesions are being followed with serial imaging. He remains clinically and neurologically asymptomatic. Conclusions: This is the first case presenting with long-term survival in a patient with metastatic anaplastic thyroid carcinoma. A multidisciplinary course with early aggressive surgical removal, adjuvant treatment with chemotherapy and radiation, and long term imaging follow up may be an acceptable treatment plan for stable patients.

Outcomes Following Breast Reconstruction in Patients With Prior Mantle Radiation for Treatment of Hodgkin's Lymphoma.

External beam radiation in the mantle field has been a mainstay of therapy for Hodgkin's lymphoma for decades. The incidence of breast cancer in patients treated with mantle radiation is known to be elevated. Few studies have examined outcomes of breast reconstruction in this high-risk group. The current study presents the largest series of immediate breast reconstruction in this population and aims to evaluate reconstructive outcomes and examine differences between implant-based and autologous reconstructions. A retrospective review of records from a 10-year period at 2 institutions was undertaken. Patients treated with mantle radiation for Hodgkin's lymphoma who subsequently underwent mastectomy with immediate reconstruction were identified. Patient demographics, clinical characteristics, and outcomes including complications and operative revisions were gathered. Univariate and multivariate analyses were conducted to assess differences between implant-based and autologous reconstructions. A total of 97 breast reconstructions were performed in 52 patients. Seventy-nine reconstructions were implant-based, and 18 were autologous. Patients with implant-based reconstructions were older than autologous reconstructions (47 ± 8.8 years vs 42 ± 6.5 years, P < 0.05). Both groups had long-term follow-up; however, the mean follow-up duration was shorter in the implant-based compared with the autologous group (5 years vs 8.3 years; P < 0.05). Otherwise, the groups were similar with respect to BMI, medical comorbidities, oncologic diagnosis, and therapy. The interval between mantle radiation and reconstruction was comparable for implant-based and autologous groups (23.4 ± 9 years vs 21.3 ± 6.1 years, P = 0.6). The overall complication rate of breast reconstruction was not statistically different between the implant-based and autologous groups (35% vs 16%, P = 0.16). Three implant-based reconstructions (3.7%) required explantation. There were no complete flap losses in the autologous group. An associated 6-fold higher rate of unplanned revisions was observed with the autologous reconstruction group compared with the implant-based reconstruction group (odds ratio, 6.09; 95% confidence interval, 1.14-32.48; P = 0.035). In this study, long-term follow-up suggests immediate breast reconstruction in patients with prior mantle radiation can be achieved safely with an acceptable complication profile utilizing either implant-based or autologous techniques. Autologous breast reconstruction is linked with a higher rate of revisions compared with implant-based breast reconstruction in this study population.

Early to Middle Jurassic San Andrés-Cedros plutonic suite, western coast of Baja California, Mexico: Geochemical and isotopic evidence for an island arc extending to the central peninsula

In the Vizcaíno peninsula and Cedros Island region, west-central part of the Baja California peninsula, México, Upper Triassic ophiolitic sequences are intruded by arc-related Mid-Jurassic plutons. We analyze the ~150 Ma old San Roque pluton (SRp) in the Vizcaíno peninsula and plutonic rocks (~165 Ma) of the Punta Norte zone (PN) in the Cedros Island. The modal composition of the almost 10 km2 extending San Roque pluton varies from biotite-hornblende quartz diorite to biotite-hornblende tonalite intruded by granodioritic dykes. Intrusive rocks are subalkaline, calcic/calc-alkaline and metaluminous, akin to island arc granite setting. The primitive initial εNd values of +8.9 and + 9 of SRp quartz diorite and tonalite are indicative of a depleted mantle source without crustal assimilation. The sequence intrudes amphibolites that are interpreted as metavolcanic remnants of the oceanic-type crust of the Vizcaíno peninsula ophiolite. One amphibolite sample is characterized as magmatically poorly evolved, with flat REE patterns, and MORB-type initial εNd values of +10.1. The PN plutonic rocks of Cedros Island crop out at its northern edge. Their modal compositions are hornblende quartz diorite, hornblende leucotonalite, and microtonalitic dykes. These rocks are classified as subalkaline, magnesian, and calcic, typical island arc granites. The REE patterns tend to be subparallel, with progressive enrichments in REE abundances, suggesting fractional crystallization resulting from the evolution of a single magmatic system. Microtonalite dykes and leucotonalite yield initial εNd values of +7.8 to +8, indicating that the PN rocks were produced from magmas associated with a depleted mantle source. These values are in agreement with the correlation of εSr(165 Ma) vs. εNd(165 Ma), where all samples plot in the depleted mantle field. The PN plutonic rocks intruded pillow basalts with basaltic dykes. Their initial εNd and εSr plot in the depleted mantle field indicative of island arc tholeiites.The SRp and PN plutonic rocks are correlated with the coeval El Arco system (~160 Ma) in the central part of the Baja California peninsula. They show the same magmatic evolution in a primitive oceanic island arc environment derived from a depleted mantle with no crustal assimilation. We suggest that all the Jurassic sequences of the southern Peninsular Ranges batholith belong to the same arc.

Partial-Breast Reirradiation with Intraoperative Radiotherapy (IORT) for Patients Affected By Breast Cancer after Prior Thoracic Radiotherapy

Mastectomy is currently recommended for patients suffering of new or recurrent breast cancer after prior thoracic radiation. The normal tissue tolerance does not permit a second full-dose course of whole breast irradiation after a second breast-conserving surgery (BCS). We retrospectively investigated the role of a second BCS followed by intraoperative radiotherapy (IORT) for patients with localized breast cancer and prior thoracic radiation. Twenty-five patients, who declined salvage mastectomy for their breast cancer after prior thoracic radiation, were treated with BCS and IORT between 2009 and 2018. Twenty patients (74%) presented breast cancer local relapse after whole breast irradiation, seven (26%) previously received mantle field irradiation for Hodgkin Lymphoma. All breast tumors/recurrences were T1 and unifocal. IORT was delivered with the low energy X-rays IntrabeamTM device (Carl Zeiss Meditec AG, Oberkochen, Germany), using a single dose of 6 Gy prescribed to a depth of 1 cm from applicator surface (20-21Gy at applicator surface). Local control (LC), mastectomy free survival (MFS), disease free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier estimator. Treatment-related toxicities were scored by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The median time from prior thoracic radiation to breast cancer presentation was 14 years (range 6-34). All patients successfully underwent BCS and partial breast reirradiation with IORT without acute toxicity. The median follow-up from IORT was 61 months (range 2-117 months). Two patients with local recurrence underwent salvage mastectomy; among whom one had a second local relapse and started chemotherapy. One patient deceased from brain metastases. No other local or distant relapses were detected. LC, MFS, DFS, and OS at five years were 94%, 92.3%, 88.2% and 94% respectively. No cases of late Grade ≥3 toxicity were registered. In our retrospective experience, BCS with IORT is a feasible option for breast preservation in patients with localized breast cancer / recurrence and prior thoracic radiation. Treatment tolerance was excellent. Prospective trials are required to confirm these preliminary findings.

Late Mesozoic East Asian magmatic province: structure, magmatic signature, formation conditions

The Late Mesozoic igneous province of East Asia in connection with global geological events is considered. The main structure-forming events and the largest magmatic productivity of the province coincided with the peak of widely manifested plume activity in the Early Cretaceous. A geodynamic model of the magmatic province formation is proposed, relating development of the province with the complex geodynamic setting for the interaction of the convergent boundary with the hot mantle field. The Pacific marginal magmatic belt was formed in front zone of convergence where accretion of terranes occurred with prevalence of supersubduction magma-forming mechanisms. In the western part of the province outside of convergence zone an intraplate volcanic areas were formed due to activity of small mantle plumes.