Radiation-induced alteration of apatite on the surface of Mars: first in situ observations with SuperCam Raman onboard Perseverance.

Planetary exploration relies considerably on mineral characterization to advance our understanding of the solar system, the planets and their evolution. Thus, we must understand past and present processes that can alter materials exposed on the surface, affecting space mission data. Here, we analyze the first dataset monitoring the evolution of a known mineral target in situ on the Martian surface, brought there as a SuperCam calibration target onboard the Perseverance rover. We used Raman spectroscopy to monitor the crystalline state of a synthetic apatite sample over the first 950 Martian days (sols) of the Mars2020 mission. We note significant variations in the Raman spectra acquired on this target, specifically a decrease in the relative contribution of the Raman signal to the total signal. These observations are consistent with the results of a UV-irradiation test performed in the laboratory under conditions mimicking ambient Martian conditions. We conclude that the observed evolution reflects an alteration of the material, specifically the creation of electronic defects, due to its exposure to the Martian environment and, in particular, UV irradiation. This ongoing process of alteration of the Martian surface needs to be taken into account for mineralogical space mission data analysis.

Multi-analytical characterization of an oncoid from a high altitude hypersaline lake using techniques employed in the Mars2020 and Rosalind Franklin missions on Mars.

In this work, a geological sample of great astrobiological interest was studied through analytical techniques that are currently operating in situ on Mars and others that will operate in the near future. The sample analyzed consisted of an oncoid, which is a type of microbialite, collected in the Salar Carachi Pampa, Argentina. The main peculiarity of microbialites is that they are organo-sedimentary deposits formed by the in situ fixation and precipitation of calcium carbonate due to the growth and metabolic activities of microorganisms. For this reason, the Carachi Pampa oncoid was selected as a Martian analog for astrobiogeochemistry study. In this sense, the sample was characterized by means of the PIXL-like, SuperCam-like and SHERLOC-like instruments, which represent instruments on board the NASA Perseverance rover, and by means of RLS-like and MOMA-like instruments, which represent instruments on board the future ESA Rosalind Franklin rover. It was possible to verify that the most important conclusions and discoveries have been obtained from the combination of the results. Likewise, it was also shown that Perseverance rover-like remote-sensing instruments allowed a first detailed characterization of the biogeochemistry of the Martian surface. With this first characterization, areas of interest for in-depth analysis with Rosalind Franklin-like instruments could be identified. Therefore, from a first remote-sensing elemental identification (PIXL-like instrument), followed by a remote-sensing molecular characterization (SuperCam and SHERLOC-like instruments) and ending with an in-depth microscopic analysis (RLS and MOMA-like instruments), a wide variety of compounds were found. On the one hand, the expected minerals were carbonates, such as aragonite, calcite and high-magnesium calcite. On the other hand, unexpected compounds consisted of minerals related to the Martian/terrestrial surface (feldspars, pyroxenes, hematite) and organic compounds related to the past biological activity related to the oncoid (kerogen, lipid biomarkers and carotenes). Considering samples resembling microbialites have already been found on Mars and that one of the main objectives of the missions is to identify traces of past life, the study of microbialites is a potential way to find biosignatures protected from the inhospitable Martian environment. In addition, it should be noted that in this work, further conclusions have been obtained through the study of the results as a whole, which could also be carried out on Mars.

A new methodology for kerogen maturity estimation based on Raman spectroscopy and chemometric analysis.

Diverse criteria or parameters have been cited as tools to determine the maturity of carbonaceous matter (CM) found in geologic samples using Raman spectroscopy. However, these approaches involve the mathematical decomposition of Raman bands which can vary with the specific method, the software employed, or even the individual user. Data should be treated spectrum by spectrum and a similar spectroscopic pre-treatment should be applied to the whole dataset. All these factors affect the final result and can introduce a wide uncertainty and bias. We propose an alternative chemometric method that avoids these sources of uncertainty by considering the entire spectrum, not just certain regions, while allowing specific regions of interest to be defined. Moreover, spectra pre-treatment is not required. We employ principal component analysis (PCA) across the whole range of spectra. While the method does not provide an absolute maturity value, it allows comparison of different CM in terms of maturity or H:C ratio. In the analysis of coal standards, samples were grouped by maturity.

Homogeneity assessment of the SuperCam calibration targets onboard rover perseverance.

The SuperCam instrument, onboard the Perseverance rover (Mars 2020 mission) is designed to perform remote analysis on the Martian surface employing several spectroscopic techniques such as Laser Induced Breakdown Spectroscopy (LIBS), Time-Resolved Raman (TRR), Time-Resolved Fluorescence (TRF) and Visible and Infrared (VISIR) reflectance. In addition, SuperCam also acquires high-resolution images using a color remote micro-imager (RMI) as well as sounds with its microphone. SuperCam has three main subsystems, the Mast Unit (MU) where the laser for chemical analysis and collection optics are housed, the Body Unit (BU) where the different spectrometers are located inside the rover, and the SuperCam Calibration Target (SCCT) located on the rover's deck to facilitate calibration tests at similar ambient conditions as the analyzed samples. To perform adequate calibrations on Mars, the 22 mineral samples included in the complex SCCT assembly must have a very homogeneous distribution of major and minor elements. The analysis and verification of such homogeneity for the 5-6 replicates of the samples included in the SCCT has been the aim of this work. To verify the physic-chemical homogeneity of the calibration targets, micro Energy Dispersive X-ray Fluorescence (EDXRF) imaging was first used on the whole surface of the targets, then the relative abundances of the detected elements were computed on 20 randomly distributed areas of 100 × 100 µm. For those targets showing a positive Raman response, micro-Raman spectroscopy imaging was performed on the whole surface of the targets at a resolution of 100 × 100 µm. The %RSD values (percent of relative standard deviation of mean values) for the major elements measured with EDXRF were compared with similar values obtained by two independent LIBS set-ups at spot sizes of 300 µm in diameter. The statistical analysis showed which elements were homogeneously distributed in the 22 mineral targets of the SCCT, providing their uncertainty values for further calibration. Moreover, nine of the 22 targets showed a good Raman response and their mineral distributions were also studied. Those targets can be also used for calibration purposes of the Raman part of SuperCam using the wavenumbers of their main Raman bands proposed in this work.

Intraoperative electron beam radiotherapy and perioperative high-dose-rate brachytherapy in previously irradiated oligorecurrent gynecological cancer: clinical outcome analysis.

BACKGROUND: Pelvic recurrences from previously irradiated gynecological cancer lack solid evidence for recommendation on salvage. METHODS: A total of 58 patients were included in this clinical analysis. Salvage surgery was performed for locoregional relapse within previously irradiated pelvic area after initial surgery and adjuvant radiotherapy or radical external beam radiotherapy. The primary tumor diagnosis included cervical cancer (n = 47, 81%), uterine cancer (n = 4, 7%), and other types (n = 7, 12%). Thirty-three patients received adjuvant IOERT (1984-2000) at a median dose of 15 Gy (range 10-20 Gy) and 25 patients received adjuvant PHDRB (2001-2016) at a median dose of 32 Gy (range 24-40 Gy) in 6, 8, or 10 b.i.d. fractions. RESULTS: The median follow-up was 5.6 years (range 0.5-14.2 years). Twenty-nine (50.0%) patients had positive surgical margins. Grade ≥ 3 toxic events were recorded in 34 (58.6%) patients. The local control rate at 2 years was 51% and remained stable up to 14 years. Disease-free survival rates at 2, 5, and 10 years were 17.2, 15.5, and 15.5%, respectively. Overall survival rates at 2, 5, and 10 years were 58.1, 17.8, and 17.8%, respectively. CONCLUSIONS: IOERT and PHDRB account for an effective salvage in oligorecurrent gynecological tumors. Patients with previous pelvic radiation suitable for salvage surgery and at risk of inadequate margins could benefit from adjuvant reirradiation in form of IOERT or PHDRB. However, the rate of severe grade ≥ 3 toxicity associated with the entire treatment program is relevant and needs to be closely counterbalanced against the expected therapeutic gain.

Characterization of sedimentary and volcanic rocks in Armintza outcrop (Biscay, Spain) and its implication for Oxia Planum (Mars) exploration.

The landing site of the next planetary mission lead by ESA (ExoMars 2022) will be Oxia Planum. This location has been chosen due to different reasons, among them, the existence of sedimentary rocks that could host remains of organic matter. The fact that this type of rocks coexists with volcanic ones makes of high importance the study of the processes and the possible interactions that could happen among them. Therefore, in this research work the Armintza outcrop (Biscay, North of Spain) is proposed as an Oxia Planum analogue since it has the dichotomy of volcanic and sedimentary rock layers that is expected on the landing site of the ExoMars 2022 mission. As Raman and visible near infrared spectroscopies will be in the payload of the rover of that mission, they have been used to characterize the samples collected in the Armintza outcrop. With the help of these techniques, feldspars (albite mainly) and phyllosilicates (kaolinite and dickite, together with micas and chlorite minerals) have been identified as the major products on the samples, together with some weathering products (carbonates, sulphates, oxides) and apatite. Moreover, remains of kerogen have been detected in the sedimentary layers in contact with the interlayered lava flows, confirming the capability of similar sedimentary-volcanic layers to trap and store organic remains for millions of years. After establishing which compounds have volcanic or sedimentary origin, and which must be considered alteration phases, we can consider Armintza as a good Oxia Planum analogue.

Development of innovative non-destructive analytical strategies for Mars Sample Return tested on Dar al Gani 735 Martian Meteorite.

This work proposes an innovative non-destructive analytical strategy, based on Confocal Raman micro-spectroscopy, High Resolution Raman Imaging and micro-X-Ray Fluorescence imaging, as part of the quick non-destructive techniques that could be used to characterize the Martian samples from the Mars Sample Return mission when back on Earth. Until that moment, Martian Meteorites are the only Martian samples in our hands to develop such Analytical Strategies. To demonstrate its capabilities, this analytical strategy has been applied to characterize the Dar al Gani 735 Martian Meteorite with the aim to identify the terrestrial and non-terrestrial alterations suffered by the meteorite as a very valuable complementary methodology to the more traditional petrographic analyses and single point measurements. The combination of these techniques allows extracting at the same time elemental, molecular and structural information of the studied area of the sample. The most relevant results on the analyzed DaG 735 shergottite thick samples revealed the presence of several altered mineral phases originated from the temperature and pressure conditions during the shock on Mars (anhydride, calcite and ilmenite), as well as from terrestrial weathering processes that degraded the meteorite from its landing on Earth (calcite and hematite in fractures together with gypsum, mirabilite and thenardite). As most of the conclusive results come from Raman spectroscopy, this study shows the potential of Raman spectroscopy as a key technique in the upcoming new explorations of Mars materials by the Rosalind Franklin rover (Exomars2022 mission from ESA) and the Perseverance rover (Mars2020 mission from NASA), where Raman spectrometers are mounted for the first time in an extra-terrestrial research in the field.

SuperCam Calibration Targets: Design and Development.

SuperCam is a highly integrated remote-sensing instrumental suite for NASA's Mars 2020 mission. It consists of a co-aligned combination of Laser-Induced Breakdown Spectroscopy (LIBS), Time-Resolved Raman and Luminescence (TRR/L), Visible and Infrared Spectroscopy (VISIR), together with sound recording (MIC) and high-magnification imaging techniques (RMI). They provide information on the mineralogy, geochemistry and mineral context around the Perseverance Rover. The calibration of this complex suite is a major challenge. Not only does each technique require its own standards or references, their combination also introduces new requirements to obtain optimal scientific output. Elemental composition, molecular vibrational features, fluorescence, morphology and texture provide a full picture of the sample with spectral information that needs to be co-aligned, correlated, and individually calibrated. The resulting hardware includes different kinds of targets, each one covering different needs of the instrument. Standards for imaging calibration, geological samples for mineral identification and chemometric calculations or spectral references to calibrate and evaluate the health of the instrument, are all included in the SuperCam Calibration Target (SCCT). The system also includes a specifically designed assembly in which the samples are mounted. This hardware allows the targets to survive the harsh environmental conditions of the launch, cruise, landing and operation on Mars during the whole mission. Here we summarize the design, development, integration, verification and functional testing of the SCCT. This work includes some key results obtained to verify the scientific outcome of the SuperCam system.

A single prior course of BCNU-cisplatin chemotherapy has a significant deleterious effect on mobilization kinetics of otherwise untreated patients.

Extensive prior treatment with cytotoxic agents is associated with impaired mobilization of hematopoietic cells. To assess the effect of a single course of standard-dose chemotherapy (CT), we compared the results of filgrastim-induced mobilization among two sequential groups of grade III-IV malignant glioma patients included in a hematopoietic transplantation program. The first group (21 patients) had never been treated with CT until 2 days after surgery, when they received a course of 100 mg/m2 BCNU (i.v.) and 100 mg intracarotid cisplatin for cytoreduction (not for mobilization). At 1 month after this CT, they were mobilized with 12 microg/kg filgrastim. The second group (22 patients) was mobilized with the same dose of filgrastim directly after the surgery, without having ever received any prior CT. The blood level of CD34+ cells was significantly lower in the CT-treated patients, both on the fourth day of filgrastim (15 vs 36 cells x 10(6)/l; P=0.01) and on the fifth (25 vs 58 cells x 10(6)/l; P=0.003), as it was the number of CD34+ cells collected per apheresis (1.3 vs 3.5 x 10(6)/l; P<0.0005). The toxic effect of a single course of BCNU-cisplatin CT led to significant impairment of the filgrastim-induced mobilization response.

[Anesthesia for the patient with cancer]. / Anestesia del paciente oncológico.

Surgery and radiotherapy provide the basis for local and regional control of cancer. The cancer patient has special characteristics that have implications for anesthesia. Tumors may involve the airways and affect ventilation, hemodynamics and intracranial pressure. Remote tumors can occur in endocrine cancer and in paraneoplastic syndromes. Other systemic complications of the cancer patient include hemostatic changes, immunosuppressant anemia and altered metabolism. Radiotherapy causes changes with anesthetic implications when treatment is directed at the head and neck, mediastinum, lung or surgical area. Chemotherapy is associated with non-specific toxic effects such as mucositis, aplasia and immunosuppression, alopecia and vascular injury; in addition, each chemical has other more specific toxic effects. Chemicals that are toxic for the heart and lungs have the greatest implications for anesthesia. Preoperative assessment should ascertain the effects caused by both the tumor and its treatment. Preparation for surgery includes improving nutrition and possibly inserting a venous port. Management during surgery depends on type of intervention and the patient's physical status, as they will determine the need for invasive monitoring and vessel access. The patient can be given antiemetic and antithrombotic prophylaxis. Important issues in postoperative care are the need for adequate analgesia; provision of early nutrition; antibiotic, antithrombotic and antiemetic prophylaxis; and prevention of ulcers caused by pressure.

[Value of Pet-18FDG in lung cancer]. / Valor de la tomografía por emisión de positrones (PET)-18FDG en el cáncer de pulmón.

INTRODUCTION: 18FDG-PET was studied in the diagnosis of malignancy of the solitary pulmonary nodule and in the early staging of non-small-cell lung cancer. PET results were compared with thoracic-abdominal computed tomography (CT) and brain magnetic resonance (MR). PATIENTS AND METHODS: Fifty-five patients with a radiologically detected solitary pulmonary nodule (54 CT, 1 plain radiography), were studied following an intravenous injection of 370 MBq 18FDG. Attenuation corrected emission data were acquired and analyzed qualitatively and semi-quantitatively. 30 non-small-cell lung cancer underwent MR. Biopsies were obtained in 48 non-small-cell lung cancer and 7 were controlled by follow-up (18 months). The staging of 43 non-small-cell lung cancer was confirmed by surgery (n = 13), mediastinoscopy (n = 9) and follow-up (n = 21). RESULTS: PET correctly diagnosed 52 solitary pulmonary nodules with 3 false positives (100% sensitivity and 75% specificity). In the mediastinal staging (N), CT and PET demonstrated a sensitivity and specificity of 46% vs. 100%, and 59.3% vs. 93.3%, respectively. In 6 patients, some visceral metastases detected by PET were not detected by CT (including 3 adrenals), whereas 2 brain metastases in MR were not diagnosed by PET. PET was considered decisive in the treatment and follow-up of 17 patients (32.7%). CONCLUSIONS: Whole body PET imaging is a cost-effective diagnostic technique that simplifies the malignant characterization of solitary pulmonary nodule and improves the early staging of non-small-cell lung cancer. In combination with CT, PET makes an outstanding contribution to the correct assessment of therapeutical decisions in these patients.

Induction platinum-based chemotherapy followed by radical hyperfractionated radiotherapy with concurrent chemotherapy in the treatment of locally advanced non-small-cell carcinoma of the lung.

This study evaluated tolerance, local control, and short-term survival in patients with locally advanced non-small-cell lung carcinoma treated with induction chemotherapy followed by radical hyperfractionated radiotherapy with concurrent chemotherapy. Thirty-one patients with stage IIIa (N2) or IIIb tumors were treated with cis-platinum-based induction chemotherapy for 1 to 4 courses followed by radical hyperfractionated radiotherapy (69.6 Gy) with concurrent chemotherapy given at the beginning and end of radiotherapy. Induction chemotherapy produced no complete responses and 18 (58%) partial responses. After completion of radiotherapy, 4 patients had complete response (13%) and 23 patients (74%) partial response. The patterns of failure were as follows: intrathoracic, 6 patients (22%); intrathoracic + distant metastasis, 6 patients (22%); distant metastasis without thoracic failure, 5 patients (19%). Six patients of the 12 with intrathoracic failure experienced in-field radiotherapy pure local failure. At the time of this analysis, 10 patients were alive and well (4 complete and 6 partial responders). Actuarial survival projected at 39 months is 35%. No benefit was observed for those patients responding to induction chemotherapy. Toxicity was as follows: grade III neutropenic fever in 4 patients (13%), grade IV neutropenia in 13 patients (42%), pneumonia in 6 patients (19%), grade III esophagitis in 4 patients (13%) and severe clinical pneumonitis in 1 patient (3%). Induction chemotherapy followed by chemoradiotherapy is feasible, and the preliminary results are encouraging. Complete response after radiotherapy appeared to be related to short-term disease-free survival, and decisions based on the response to chemotherapy may be equivocal.

[Intensive chemotherapy in the treatment of patients with metastatic breast cancer]. / Quimioterapia intensiva en el tratamiento de pacientes con cáncer de mama metastásico.

PURPOSE: Phase II study with intensive chemotherapy and autologous stem cells support in patients with metastatic breast cancer. METHODS: Forty-nine patients were treated with high-doses of two cytotoxic drugs and support with stem cells obtained from several leukapheresis without movilitation. The cells were reinfused forty-eight hours after finishing the administration of chemotherapy. RESULTS: Twenty-one patients (47%, CI-95%: 32.4-63.3%) achieved a complete remission. The objective responses rate was 73% (CI-95%: 57.2-85%). Overall and progression-free survival up to 4 years were 31% and 20%, respectively. Ten patients remain progression-free among 17 and 46 months. The most frequent extramedullary toxicity was hepatic and renal. Three patients (6%) died during the procedure. CONCLUSIONS: Intensive chemotherapy with hematopoietic support yields, with a moderate toxicity, a high objective response and complete remission rate. A small group of patients achieves a long progression-free survival.

Cisplatin, mitomycin, and vindesine followed by intraoperative and postoperative radiotherapy for stage III non-small cell lung cancer: final results of a phase II study.

Sixty-two patients with stage III non-small cell lung cancer (NSCLC) were treated with neoadjuvant chemotherapy consisting of cisplatin 120 mg/m2 day 1, mitomycin 8 mg/m2 day 1, and vindesine 3 mg/m2 days 1 and 14. Each cycle was repeated every 4 weeks for a total of 1 to 6 cycles (median, 3 cycles). Resection was attempted 4 to 5 weeks after the last course of chemotherapy. Intraoperative radiation therapy (IORT) (10-15 Gy) was delivered during surgery and postoperative external beam radiotherapy (EBRT) (46 Gy) was begun 4 weeks after surgery. Fifty-five patients (25 IIIA, 30 IIIB) were evaluable. Only partial responses occurred (64%), and 29 patients (53%) underwent resection. Complete resection rates were 85% (12/14) and 40% (6/15) in stage IIIA and IIIB, respectively (p = 0.01). In 3 of 29 patients (10%), no tumor was found in the resected specimen. There was one chemotherapy-related death and three postoperative-related deaths. The median survival time was 10 months, and the 5-year survival rate was 29 and 7% for stage IIIA and stage IIIB, respectively (p = 0.3). High complete resection rates and modest increase in 5-year survival have been observed in stage IIIA NSCLC. Although a number of stage IIIB patients can be made technically resectable, the low complete resectability rate reflects the lack of survival benefit in these patients.

Results of two sequential phase II studies of interleukin-2 (IL2) in metastatic renal cell carcinoma and melanoma: high-dose continuous intravenous IL2 infusion and subcutaneous IL2 administration in combination with alpha interferon.

The results of two sequential trials, the first one with high dose interleukin 2 (IL2) by continuous intravenous infusion and the second one with subcutaneous IL2 and alpha-interferon (alpha IFN), performed in consecutive patients with metastatic melanoma and renal carcinoma at the Clinica Universitaria de Navarra are presented. In the high-dose continuous IL2 trial, recombinant IL2, 18 x 10(6) IU/m2, was administered daily by continuous infusion five days a week for two weeks, and the treatment cycle was repeated after a rest of 2 weeks. Twenty two patients were treated and objective responses were observed in 3 (13.3%). Toxicity was frequent and severe, and all but one required dose reduction. The mortality rate was 9% (2/22). In the subcutaneous IL2 and alpha IFN trial, subcutaneous IL2, 4.8 x 10(6) IU/m2, was administered daily, five days a week, for 3 consecutive weeks. IL2 dose was given every 8 hours on the first day and every 12 hours on the second day, as a loading induction dose. Concomitant alpha-IFN, 3 x 10(6) IU/m2 was given subcutaneously once a day on days 1, 3 and 5 weekly each week for the duration of IL2 therapy. Of the 24 patients treated with this combination, 3 partial responses were noticed (12.5%) and the toxicity was mild to moderate. These results suggest that both, IL2 alone or IL2 in combination with alpha-IFN are minimally active and that any improvement in tolerance might impair its antitumor activity.

High-dose BCNU and autologous progenitor cell transplantation given with intra-arterial cisplatinum and simultaneous radiotherapy in the treatment of high-grade gliomas: benefit for selected patients.

A phase II study of postoperative high-dose carmustine (HDBCNU), intracarotid cisplatin (CDDP), and radical radiotherapy in patients with high-grade glioma was performed. Patients underwent 4-6 consecutive days of blood hematopoietic progenitor cell (HPC) apheresis without prior mobilization. Chemotherapy included intracarotid CDDP, 60 mg/m2, and BCNU, 900 mg/m2. HPC were infused 48 h after HDBCNU. Whole brain irradiation, up to 50 Gy, was started on the 8th day after HPC infusion. With a median follow-up time of 44 months, median overall survival was 15.5 months. Eight patients (23.5%) are alive free of disease 2-6 years after treatment (seven out of 25 patients with glioblastoma multiforme and one out of nine patients with anaplastic astrocytoma). Survival was influenced by young age, good performance and complete surgical resection. Two patients (5.8%) died of therapy-related complications. Acute hematological toxicity of HDBCNU was moderate, with a full recovery on day 26. No acute pulmonary or hepatic toxicity was found. Late severe neurological toxicity was observed in one third of patients surviving beyond 2 years. We conclude that HDBCNU, 900 mg/m2, intracarotid CDDP and radical radiotherapy appear to benefit some patients with high-grade gliomas, and phase III studies should preferentially select young patients with resectable tumors.