Untargeted Metabolomic Study of Lung Cancer Patients after Surgery with Curative Intent.

Lung cancer (LC) is a leading cause of mortality, claiming more than 1.8 million deaths per year worldwide. Surgery is one of the most effective treatments when the disease is in its early stages. The study of metabolic alterations after surgical intervention with curative intent could be used to assess the response to treatment or the detection of cancer recurrence. In this study, we have evaluated the metabolomic profile of serum samples (n = 110) from preoperative (PRE) and postoperative (POST) LC patients collected at two different time points (1 month, A; 3-6 months, B) with respect to healthy people. An untargeted metabolomic platform based on reversed phase (RP) and hydrophilic interaction chromatography (HILIC), using ultra-high performance liquid chromatography (UHPLC) and mass spectrometry (MS), was applied (MassIVE ID MSV000092213). Twenty-two altered metabolites were annotated by comparing all the different studied groups. DG(14,0/22:1), stearamide, proline, and E,e-carotene-3,3'-dione were found altered in PRE, and their levels returned to those of a baseline control group 3-6 months after surgery. Furthermore, 3-galactosyllactose levels remained altered after intervention in some patients. This study provides unique insights into the metabolic profiles of LC patients after surgery at two different time points by combining complementary analytical methods.

A 20-year Follow-up of the International Early Lung Cancer Action Program (I-ELCAP).

Background The low-dose CT (≤3 mGy) screening report of 1000 Early Lung Cancer Action Program (ELCAP) participants in 1999 led to the International ELCAP (I-ELCAP) collaboration, which enrolled 31 567 participants in annual low-dose CT screening between 1992 and 2005. In 2006, I-ELCAP investigators reported the 10-year lung cancer-specific survival of 80% for 484 participants diagnosed with a first primary lung cancer through annual screening, with a high frequency of clinical stage I lung cancer (85%). Purpose To update the cure rate by determining the 20-year lung cancer-specific survival of participants diagnosed with first primary lung cancer through annual low-dose CT screening in the expanded I-ELCAP cohort. Materials and Methods For participants enrolled in the HIPAA-compliant prospective I-ELCAP cohort between 1992 and 2022 and observed until December 30, 2022, Kaplan-Meier survival analysis was used to determine the 10- and 20-year lung cancer-specific survival of participants diagnosed with first primary lung cancer through annual low-dose CT screening. Eligible participants were aged at least 40 years and had current or former cigarette use or had never smoked but had been exposed to secondhand tobacco smoke. Results Among 89 404 I-ELCAP participants, 1257 (1.4%) were diagnosed with a first primary lung cancer (684 male, 573 female; median age, 66 years; IQR, 61-72), with a median smoking history of 43.0 pack-years (IQR, 29.0-60.0). Median follow-up duration was 105 months (IQR, 41-182). The frequency of clinical stage I at pretreatment CT was 81% (1017 of 1257). The 10-year lung cancer-specific survival of 1257 participants was 81% (95% CI: 79, 84) and the 20-year lung cancer-specific survival was 81% (95% CI: 78, 83), and it was 95% (95% CI: 91, 98) for 181 participants with pathologic T1aN0M0 lung cancer. Conclusion The 10-year lung cancer-specific survival of 80% reported in 2006 for I-ELCAP participants enrolled in annual low-dose CT screening and diagnosed with a first primary lung cancer has persisted, as shown by the updated 20-year lung cancer-specific survival for the expanded I-ELCAP cohort. © RSNA, 2023 See also the editorials by Grenier and by Sequist and Olazagasti in this issue.

Metallomic Signatures of Lung Cancer and Chronic Obstructive Pulmonary Disease.

Lung cancer (LC) is the leading cause of cancer deaths, and chronic obstructive pulmonary disease (COPD) can increase LC risk. Metallomics may provide insights into both of these tobacco-related diseases and their shared etiology. We conducted an observational study of 191 human serum samples, including those of healthy controls, LC patients, COPD patients, and patients with both COPD and LC. We found 18 elements (V, Al, As, Mn, Co, Cu, Zn, Cd, Se, W, Mo, Sb, Pb, Tl, Cr, Mg, Ni, and U) in these samples. In addition, we evaluated the elemental profiles of COPD cases of varying severity. The ratios and associations between the elements were also studied as possible signatures of the diseases. COPD severity and LC have a significant impact on the elemental composition of human serum. The severity of COPD was found to reduce the serum concentrations of As, Cd, and Tl and increased the serum concentrations of Mn and Sb compared with healthy control samples, while LC was found to increase Al, As, Mn, and Pb concentrations. This study provides new insights into the effects of LC and COPD on the human serum elemental profile that will pave the way for the potential use of elements as biomarkers for diagnosis and prognosis. It also sheds light on the potential link between the two diseases, i.e., the evolution of COPD to LC.

Inhaled corticosteroids, COPD, and the incidence of lung cancer: a systematic review and dose response meta-analysis.

BACKGROUND: There has been debate on whether inhaled corticosteroids (ICS) reduce the incidence of lung cancer amongst patients with Chronic Obstructive Lung Disease (COPD). We aimed to perform a systematic review and dose-response meta-analysis on available observational data. METHODS: We performed both a dose response and high versus low random effects meta-analysis on observational studies measuring whether lung cancer incidence was lower in patients using ICS with COPD. We report relative risk (RR) with 95% confidence intervals (CI), as well as risk difference. We use the GRADE framework to report our results. RESULTS: Our dose-response suggested a reduction in the incidence of lung cancer for every 500 ug/day of fluticasone equivalent ICS (RR 0.82 [95% 0.68-0.95]). Using a baseline risk of 7.2%, we calculated risk difference of 14 fewer cases per 1000 ([95% CI 24.7-3.8 fewer]). Similarly, our results suggested that for every 1000 ug/day of fluticasone equivalent ICS, there was a larger reduction in incidence of lung cancer (RR 0.68 [0.44-0.93]), with a risk difference of 24.7 fewer cases per 1000 ([95% CI 43.2-5.4 fewer]). The certainty of the evidence was low to very low, due to risk of bias and inconsistency. CONCLUSION: There may be a reduction in the incidence for lung cancer in COPD patients who use ICS. However, the quality of the evidence is low to very low, therefore, we are limited in making strong claims about the true effect of ICS on lung cancer incidence.

Charge transfer from Eu2+ to trivalent lanthanide co-dopants: Systematic behavior across the series.

Electron transfer processes between lanthanide activators are crucial for the functional behavior and performance of luminescent materials. Here, a multiconfigurational ab initio study reveals how direct metal-to-metal charge transfer (MMCT) between the Eu2+ luminescence activator and a Ln3+ co-dopant (Ln3+ = Ce3+, Pr3+, Nd3+, Pm3+, Sm3+, Eu3+, Gd3+, Tb3+, Dy3+, Ho3+, Er3+, Tm3+, and Yb3+) systematically dictates the luminescence and optical properties of CaF2. The combination of the structures and energies of the electronic manifolds, the vibrational force constants, and the structural properties of the donor and acceptor in the host determines the predictions of five different behaviors of CaF2:Eu2+, Ln3+ co-doped materials after MMCT absorption: formation of stable traps, MMCT emission, emission quenching, Ln3+ emission, and Eu2+ emission.

Modern quantum chemistry with [Open]Molcas.

MOLCAS/OpenMolcas is an ab initio electronic structure program providing a large set of computational methods from Hartree-Fock and density functional theory to various implementations of multiconfigurational theory. This article provides a comprehensive overview of the main features of the code, specifically reviewing the use of the code in previously reported chemical applications as well as more recent applications including the calculation of magnetic properties from optimized density matrix renormalization group wave functions.

Sleep Disordered Breathing Is Highly Prevalent in Patients with Lung Cancer: Results of the Sleep Apnea in Lung Cancer Study.

BACKGROUND: Obstructive sleep apnea (OSA) has been linked to tumorigenesis and tumor progression. OBJECTIVES: The Sleep Apnea in Lung Cancer (SAIL) study (NCT02764866) was designed to determine the prevalence of OSA in patients with lung cancer. METHODS: Cross-sectional study including consecutive patients with newly diagnosed lung cancer. All patients were offered home sleep apnea testing (HSAT) and administered a sleep-specific questionnaire prior to initiating oncologic treatment. Sleep study-related variables, symptoms, and epidemiologic data as well as cancer related variables were recorded. RESULTS: Eighty-three patients were enrolled in the SAIL study. Sixty-six completed HSAT. The mean age was 68 ± 11 years and 58% were male with a mean body mass index of 28.1 ± 5.4. Forty-seven percent were current smokers, 42% former smokers, and 11% never smokers with a median tobacco consumption of 51 pack-years. Fifty percent had COPD with a mean FEV1 of 83 ± 22.6% of predicted and a mean DLCO of 85.5 ± 20.1%. Adenocarcinoma was the most common histologic type (46.7%), followed by squamous cell (16.7%) and small cell (16.7%). Most patients were diagnosed at an advanced stage (65% in stages III-IV). The vast majority (80%) had OSA (apnea-hypopnea index [AHI] > 5), and 50% had moderate to severe OSA (AHI > 15) with a mean Epworth Sleepiness Score of 7.43 ± 3.85. Significant nocturnal hypoxemia was common (Median T90: 10.9% interquartile range 2.4-42.2). CONCLUSIONS: Sleep apnea and nocturnal hypoxemia are highly prevalent in patients with lung cancer.

Understanding the Links Between Lung Cancer, COPD, and Emphysema: A Key to More Effective Treatment and Screening.

Lung cancer has been linked to the changes in lung function characteristic of chronic obstructive pulmonary disease (COPD) and to the changes in lung morphology seen in emphysema. It seems that a common thread of smoking-induced lung injury can be traced to all three diseases. However, the association is not as straightforward as it may seem; for example, even never-smokers with emphysema have an increased risk of lung cancer. Whether lung cancer, COPD, and emphysema are linked by common genes, mechanisms, causes, or a combination thereof, understanding the associations between them has become a priority for research regarding tobacco-related illnesses. A better delineation of the relationships between these three entities may lead to significant improvements in the effectiveness of lung cancer screening programs, and to reductions in the morbidity and mortality associated with these deadly diseases.

A Prospective Randomized Study Comparing Manual and Wall Suction in the Performance of Bronchoalveolar Lavage.

BACKGROUND: Bronchoalveolar lavage (BAL) may be performed using a hand-held syringe or wall suction. OBJECTIVES: The aim was to study BAL volume and diagnostic yields based on BAL technique. METHODS: A total of 220 consecutive patients undergoing BAL at our center were included. Manual aspiration was performed in 115 patients (group 1), and wall suction (<50 mm Hg of negative pressure) was used in 105 patients (group 2). All bronchoscopies were performed under conscious sedation applying topical anesthesia with lidocaine. Three 50-ml sterile saline aliquots were instilled in all patients. RESULTS: The mean total amount of fluid recovered was 67 ± 20 ml in group 1 and 55 ± 22 ml in group 2 (p < 0.001). More patients in the manual aspiration group met American Thoracic Society criteria (recovery of ≥30% of instilled fluid) for an optimal BAL (81 vs. 59%; p < 0.001). The quantity of recovered fluid was also related to BAL location (p < 0.001) and radiologic findings (p = 0.002). Forty-eight (22%) BALs were diagnostic (23 in group 1 and 25 in group 2), including 37 positive bacterial cultures, 6 positive stains for Pneumocystis, and 5 cases of malignancy. No statistically significant difference in diagnostic yield was observed between the two groups. A BAL diagnosis was more likely in patients with certain radiologic (p = 0.033) and endoscopic findings (p = 0.001). When taking into account all bronchoscopic techniques performed during the procedure (e.g. biopsies, brushing, etc.), bronchoscopy was diagnostic in 37% of patients. CONCLUSIONS: Manual aspiration is superior to wall suction during BAL yielding a larger quantity of aspirate. Diagnostic yields are similar for both techniques.

Improving selection criteria for lung cancer screening. The potential role of emphysema.

RATIONALE: Lung cancer (LC) screening using low-dose chest computed tomography is now recommended in several guidelines using the National Lung Screening Trial (NLST) entry criteria (age, 55-74; ≥30 pack-years; tobacco cessation within the previous 15 yr for former smokers). Concerns exist about their lack of sensitivity. OBJECTIVES: To evaluate the performance of NLST criteria in two different LC screening studies from Europe and the United States, and to explore the effect of using emphysema as a complementary criterion. METHODS: Participants from the Pamplona International Early Lung Action Detection Program (P-IELCAP; n = 3,061) and the Pittsburgh Lung Screening Study (PLuSS; n = 3,638) were considered. LC cumulative frequencies, incidence densities, and annual detection rates were calculated in three hypothetical cohorts, including subjects who met NLST criteria alone, those with computed tomography-detected emphysema, and those who met NLST criteria and/or had emphysema. MEASUREMENTS AND MAIN RESULTS: Thirty-six percent and 59% of P-IELCAP and PLuSS participants, respectively, met NLST criteria. Among these, higher LC incidence densities and detection rates were observed. However, applying NLST criteria to our original cohorts would miss as many as 39% of all LC. Annual screening of subjects meeting either NLST criteria or having emphysema detected most cancers (88% and 95% of incident LC of P-IELCAP and PLuSS, respectively) despite reducing the number of screened participants by as much as 52%. CONCLUSIONS: LC screening based solely on NLST criteria could miss a significant number of LC cases. Combining NLST criteria and emphysema to select screening candidates results in higher LC detection rates and a lower number of cancers missed.

Configuration coordinate energy level diagrams of intervalence and metal-to-metal charge transfer states of dopant pairs in solids.

Configuration coordinate diagrams, which are normally used in a qualitative manner for the energy levels of active centers in phosphors, are quantitatively obtained here for intervalence charge transfer (IVCT) states of mixed valence pairs and metal-to-metal charge transfer (MMCT) states of heteronuclear pairs, in solid hosts. The procedure relies on vibrational frequencies and excitation energies of single-ion active centers, and on differences between ion-ligand distances of the donor and the acceptor, which are attainable empirically or through ab initio calculations. The configuration coordinate diagrams of the Yb(2+)/Yb(3+) mixed-valence pair in Yb-doped YAG and the Ce(3+)/Yb(3+) heteronuclear pair in Ce,Yb-codoped YAG, are obtained and described. They are drawn from empirical data of the single-ions and their usefulness is discussed. The first diagram suggests that IVCT states of Yb(2+)/Yb(3+) pairs may play an important role in the quenching of the Yb(3+) emission and it provides the details of the quenching mechanism. The second diagram supports the interpretation recently given for the energy transfer from Ce(3+) to Yb(3+) in Ce,Yb-codoped YAG via a MMCT Ce(4+)-Yb(2+) state and it provides the details. The analyses of the two diagrams suggest the formation of Yb(2+)/Yb(3+) pairs after the Ce(3+)-to-Yb(3+) MMCT, which is responsible for the temperature quenching of the Yb(3+) emission excited via Ce(3+) (4f → 5d) absorption in Ce,Yb-codoped YAG.

Resolving the ambiguity in the relation between Stokes shift and Huang-Rhys parameter.

Electronic transitions in luminescent molecules or centers in crystals couple to vibrations. This results in broadening of absorption and emission bands, as well as in the occurence of a Stokes shift EStokes. In principle, one can derive from EStokes the Huang-Rhys parameter S, which describes the microscopic details of the vibrational coupling and can be related to the equilibrium position offset ΔQe between the ground state and excited state. The commonly used textbook relations EStokes = (2S - 1)ℏω and EStokes = 2Sℏω are only approximately valid. In this paper we investigate how EStokes is related to S, taking into account the effects of a finite temperature. We show that in different ranges of temperature, different approximate relations between EStokes and S are appropriate. Moreover, we demonstrate that the difference between the barycenters of absorption and emission bands can be used to determine S in an unambiguous way. The position of the barycenter is, contrary to the Stokes shift, unaffected by temperature.

Metal-to-metal charge transfer between dopant and host ions: Photoconductivity of Yb-doped CaF2 and SrF2 crystals.

Dopant-to-host electron transfer is calculated using ab initio wavefunction-based embedded cluster methods for Yb/Ca pairs in CaF2 and Yb/Sr pairs in SrF2 crystals to investigate the mechanism of photoconductivity. The results show that, in these crystals, dopant-to-host electron transfer is a two-photon process mediated by the 4f(N-1)5d excited states of Y b(2+): these are reached by the first photon excitation; then, they absorb the second photon, which provokes the Y b(2+) + Ca(2+) (Sr(2+)) → Y b(3+) + Ca(+) (Sr(+)) electron phototransfer. This mechanism applies to all the observed Y b(2+) 4f-5d absorption bands with the exception of the first one: Electron transfer cannot occur at the first band wavelengths in CaF2:Y b(2+) because the Y b(3+)-Ca(+) states are not reached by the two-photon absorption. In contrast, Yb-to-host electron transfer is possible in SrF2:Y b(2+) at the wavelengths of the first 4f-5d absorption band, but the mechanism is different from that described above: first, the two-photon excitation process occurs within the Y b(2+) active center, then, non-radiative Yb-to-Sr electron transfer can occur. All of these features allow to interpret consistently available photoconductivity experiments in these materials, including the modulation of the photoconductivity by the absorption spectrum, the differences in photoconductivity thresholds observed in both hosts, and the peculiar photosensitivity observed in the SrF2 host, associated with the lowest 4f-5d band.

Blue absorption and red emission of Bi2+ in solids: strongly spin-orbit coupled 6p levels in low symmetry fields.

Wave function embedded cluster ab initio calculations on a (BiO8)(14-) cluster under the effects of a high symmetry Oh confinement potential are used to study the energies of the (2)P1/2, (2)P3/2(1), and (2)P3/2(2) spin-orbit coupling levels of the 6s(2)6p configuration of Bi(2+) in Oh, D4h, D2h, D4, D2d, D2, S4, C4v, C4, C3v, C2v, C2, Cs, and C1 fields, together with the (2)P1/2→(2)P3/2(1) and (2)P1/2→(2)P3/2(2) absorption oscillator strengths and the (2)P3/2(1) radiative lifetime. These levels are responsible for the blue absorptions and the red-orange emissions produced when Bi(2+) is doped in borates, phosphates, sulphates, and other hosts. It is found that the splitting of (2)P3/2 is mainly due to the tetragonal D4h and orthorhombic D2h components of the actual field. It is enhanced by Bi going towards two or four ligands. The intensities of the (2)P1/2→(2)P3/2(1) and (2)P1/2→(2)P3/2(2) absorptions are mostly induced by the Bi displacements and by tetragonal scalenoidal D2d fields. The most favorable fields for a large splitting of the (2)P3/2 level that can drive a red shift of the (2)P3/2(1) →(2)P1/2 emission are the C2v and Cs fields resulting from the combination of D2h orthorhombic fields and Bi approaching two or four ligands on the main orthorhombic planes.

Large splittings of the 4f shell of Ce3+ in garnets.

Ab initio embedded cluster calculations on Ce(3+)-doped Y3Al5O12, Lu3Al5O12, Gd3Al5O12, Y3Ga5O12, Lu3Ga5O12, and Gd3Ga5O12, which do not make use of any adjustable parameter, support recent assignments of the seventh 4f level of Ce(3+) in garnets [Przybylinska et al., Appl. Phys. Lett., 2013, 102, 241112] and that the splitting of the 4f shell of Ce(3+) in these materials is slightly smaller than 4000 cm(-1) and much larger than the 2000-2500 cm(-1) commonly assumed in analyses of 5d → 4f emission bands. Why this wrong assumption has been working well so far is explained by the fact that the intensity of the emission to the seventh level of the 4f(1) configuration is found to be only one hundredth of the integrated intensity of the emissions to the other six levels, which group themselves into two sets of three individual levels separated by 2000-2500 cm(-1). The effective field splitting and the spin-orbit coupling splitting are found to be of the same size. From a strong field coupling point of view, the first six levels result from the interactions between (2)T(2u) and (2)T(1u) cubic levels and the higher, isolated seventh level comes directly from the cubic (2)A(2u). From a weak field coupling point of view, the first three levels result from the splitting of (2)F(5/2), the second three levels from the splitting of (2)F(7/2) and the seventh level from a strong, cubic field driven interaction between (2)F(7/2) and (2)F(5/2) components [Herrmann et al., J. Appl. Phys., 1966, 37, 1312].

Ab initio theoretical study on the 4f(2) and 4f5d electronic manifolds of cubic defects in CaF2:Pr3+.

Wave function-based embedded cluster ab initio calculations have been carried out in order to study the 4f(2) and 4f5d energy levels of the cubic substitutional defect of Pr-doped CaF2. The 4f(2) → 4f5d absorption spectrum and 4f5d → 4f(2) emission spectrum have been calculated. The 4f(2 1)S0 level is found to be immersed in the 4f5d(eg) manifold, so that no quantum cutting from (1)S0 can occur and only strong 4f5d(eg) → 4f(2) emission is predicted, which supports previous assumptions made in order to explain results in CaF2:Pr(3+). The details of the 4f(2) → 4f5d(eg) and 4f(2) → 4f5d(t2g) bands of the absorption spectrum are interpreted and assignments are made. The lowest level of the 4f5d(eg) configuration is found to have 80% of singlet character, in opposition to Hund's Rules, and the issue is discussed in detail. The comparison between the experimental 4f5d(eg) → 4f(2) high resolution emission spectrum of the cubic site of CaF2:Pr(3+) and the calculated emission spectra from the two lowest 4f5d(eg) states 1T2u((1)T2u) and 1Eu(1(3)T2u) suggests the possibility that the experimental emission of the cubic Pr defect of CaF2:Pr(3+) is in fact a multiple emission.

Intervalence charge transfer luminescence: interplay between anomalous and 5d - 4f emissions in Yb-doped fluorite-type crystals.

In this paper, we report the existence of intervalence charge transfer (IVCT) luminescence in Yb-doped fluorite-type crystals associated with Yb(2+)-Yb(3+) mixed valence pairs. By means of embedded cluster, wave function theory ab initio calculations, we show that the widely studied, very broad band, anomalous emission of Yb(2+)-doped CaF2 and SrF2, usually associated with impurity-trapped excitons, is, rather, an IVCT luminescence associated with Yb(2+)-Yb(3+) mixed valence pairs. The IVCT luminescence is very efficiently excited by a two-photon upconversion mechanism where each photon provokes the same strong 4f(14)-1A1g→ 4f(13)((2)F7/2)5deg-1T1u absorption in the Yb(2+) part of the pair: the first one, from the pair ground state; the second one, from an excited state of the pair whose Yb(3+) moiety is in the higher 4f(13)((2)F5/2) multiplet. The Yb(2+)-Yb(3+) → Yb(3+)-Yb(2+) IVCT emission consists of an Yb(2+) 5deg → Yb(3+) 4f7/2 charge transfer accompanied by a 4f7/2 → 4f5/2 deexcitation within the Yb(2+) 4f(13) subshell: [(2)F5/25deg,(2)F7/2] → [(2)F7/2,4f(14)]. The IVCT vertical transition leaves the oxidized and reduced moieties of the pair after electron transfer very far from their equilibrium structures; this explains the unexpectedly large band width of the emission band and its low peak energy, because the large reorganization energies are subtracted from the normal emission. The IVCT energy diagrams resulting from the quantum mechanical calculations explain the different luminescent properties of Yb-doped CaF2, SrF2, BaF2, and SrCl2: the presence of IVCT luminescence in Yb-doped CaF2 and SrF2; its coexistence with regular 5d-4f emission in SrF2; its absence in BaF2 and SrCl2; the quenching of all emissions in BaF2; and the presence of additional 5d-4f emissions in SrCl2 which are absent in SrF2. They also allow to interpret and reproduce recent experiments on transient photoluminescence enhancement in Yb(2+)-doped CaF2 and SrF2, the appearance of Yb(2+) 4f-5d absorption bands in the excitation spectra of the IR Yb(3+) emission in partly reduced CaF2:Yb(3+) samples, and to identify the broadband observed in the excitation spectrum of the so far called anomalous emission of SrF2:Yb(2+) as an IVCT absorption, which corresponds to an Yb(2+) 4f5/2 → Yb(3+) 4f7/2 electron transfer.

Intervalence charge transfer luminescence: the anomalous luminescence of cerium-doped Cs2LiLuCl6 elpasolite.

The existence of intervalence charge transfer (IVCT) luminescence is reported. It is shown that the so called anomalous luminescence of Ce-doped elpasolite Cs2LiLuCl6, which is characterized mainly by a very large Stokes shift and a very large band width, corresponds to an IVCT emission that takes place in Ce(3+)-Ce(4+) pairs, from the 5de(g) orbital of Ce(3+) to 4f orbitals of Ce(4+). Its Stokes shift is the sum of the large reorganization energies of the Ce(4+) and Ce(3+) centers formed after the fixed-nuclei electron transfer and it is equal to the energy of the IVCT absorption commonly found in mixed-valence compounds, which is predicted to exist in this material and to be slightly larger than 10,000 cm(-1). The large band width is the consequence of the large offset between the minima of the Ce(3+)-Ce(4+) and Ce(4+)-Ce(3+) pairs along the electron transfer reaction coordinate. This offset is approximately 2√3 times the difference of Ce-Cl equilibrium distances in the Ce(3+) and Ce(4+) centers. It is shown that the energies of the peaks and the widths of IVCT absorption and emission bands can be calculated ab initio with reasonable accuracy from diabatic energy surfaces of the ground and excited states and that these can be obtained, in turn, from independent calculations on the donor and acceptor active centers. We obtained the energies of the Ce(3+) and Ce(4+) active centers of Ce-doped Cs2LiLuCl6 by means of state-of-the-art wave-function-theory spin-orbit coupling relativistic calculations on the donor cluster (CeCl6Li6Cs8)(11+) and the acceptor cluster (CeCl6Li6Cs8)(12+) embedded in a quantum mechanical embedding potential of the host. The calculations provide interpretations of unexplained experimental observations as due to higher energy IVCT absorptions, and allow to reinterpret others. The existence of another IVCT emission of lower energy, at around 14,000-16,000 cm(-1) less than the 5dt(2g) emission, is also predicted.