Cost-effectiveness analysis of durvalumab, tremelimumab, and etoposide-platinum in first-line treatment of extensive-stage small cell lung cancer.

BACKGROUND: Durvalumab plus etoposide-platinum (DEP) showed sustained overall survival improvements in patients with extensive-stage small-cell lung cancer (ES-SCLC) compared to etoposide-platinum (EP), but adding tremelimumab to DEP (DTEP) did not significantly improve outcomes. A third-party payer perspective is taken here to evaluate the cost-effectiveness of DTEP, DEP, and EP for ES-SCLC. METHODS: The cost-effectiveness was evaluated by partitioning survival models into 3 mutually exclusive health states. In this model, clinical characteristics and outcomes were obtained from the CASPIAN. Model robustness was evaluated through 1-way deterministic and probabilistic sensitivity analyses. Outcome measurements included costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio, life-years, incremental net health benefit, and incremental net monetary benefit. The analysis was conducted with a 10-year lifetime horizon in a United States setting. RESULTS: Compared with EP, DEP, and DTEP were associated with an increment of 0.480 and 0.313 life-years, and an increment of 0.247 and 0.165 QALYs, as well as a $139,788 and $170,331 increase in cost per patient. The corresponding ICERs were $565,807/QALY and $1033,456/QALY, respectively. The incremental net health benefit and incremental net monetary benefit of DEP or DTEP were -0.685 QALYs and -$102,729, or -0.971 QALYs and -$145,608 at a willingness to pay threshold of $150,000/QALY, respectively. Compared with DTEP, DEP was dominated. DTEP and DEP were 100% unlikely to be cost-effective if the willingness to pay threshold was $150,000/QALY. DEP was cost-effective compared to EP when durvalumab was priced below $0.994/mg. Compared with EP, DEP, and DTEP were unlikely to be considered cost-effective across all subgroups. CONCLUSION: DEP and DTEP were not cost-effective options in the first-line treatment for ES-SCLC compared with EP, from the third-party payer perspective in the United States. Compared with DTEP, DEP was dominated.

Regional shear wave speeds track regional axial stress in nonuniformly loaded fibrous soft tissues.

Ligaments and tendons undergo nonuniform deformation during movement. While deformations can be imaged, it remains challenging to use such information to infer regional tissue loading. Shear wave tensiometry is a promising noninvasive technique to gauge axial stress and is premised on a tensioned beam model. However, it is unknown whether tensiometry can predict regional stress in a nonuniformly loaded structure. The objectives of this study were to (1) determine whether regional shear wave speed tracks regional axial stress in nonuniformly loaded fibrous soft tissues, and (2) determine the sensitivity of regional axial stress and shear wave speed to nonuniform load distribution and fiber alignment. We created a representative set of 12,000 dynamic finite element models of a fibrous soft tissue with probabilistic variations in fiber alignment, stiffness, and aspect ratio. In each model, we applied a randomly selected nonuniform load distribution, and then excited a shear wave and tracked its regional propagation. We found that regional shear wave speed was an excellent predictor of the regional axial stress (RMSE = 0.57 MPa) and that the nature of the regional shear wave speed-stress relationship was consistent with a tensioned beam model (R2 = 0.99). Variations in nonuniform load distribution and fiber alignment did not substantially alter the wave speed-stress relationship, particularly at higher loads. Thus, these findings suggests that shear wave tensiometry could provide a quantitative estimate of regional tissue stress in ligaments and tendons.

Real-life clinical management patterns in extensive-stage small cell lung cancer across France: a multi-method study.

BACKGROUND: We designed this study based on both a physician practice survey and real-world patient data to: (1) evaluate clinical management practices in extensive-stage small cell lung cancer (ES-SCLC) among medical centers located across France; and (2) describe first-line treatment patterns among patients with ES-SCLC following the introduction of immunotherapy into clinical practice. METHODS: A 50-item questionnaire was completed by physicians from 45 medical centers specialized in SCLC management. Responses were collected from June 2022 to January 2023. The survey questions addressed diagnostic workup of ES-SCLC, chemoimmunotherapy in first-line and second-line settings, and use of prophylactic cranial irradiation (PCI) and radiotherapy. In parallel, using a chart review approach, we retrospectively analyzed aggregated information from 548 adults with confirmed ES-SCLC receiving first-line treatment in the same centers. RESULTS: In ES-SCLC, treatment planning is based on chest computed tomography (CT) (as declared by 100% of surveyed centers). Mean time between diagnosis and treatment initiation was 2-7 days, as declared by 82% of centers. For detection of brain metastases, the most common imaging test was brain CT (84%). The main exclusion criteria for first-line immunotherapy in the centers were autoimmune disease (87%), corticosteroid therapy (69%), interstitial lung disease (69%), and performance status ≥ 2 (69%). Overall, 53% and 36% of centers considered that patients are chemotherapy-sensitive if they relapse within ≥ 3 months or ≥ 6 months after first-line chemoimmunotherapy, respectively. Among the 548 analyzed patients, 409 (75%) received chemoimmunotherapy as a first-line treatment, 374 (91%) of whom received carboplatin plus etoposide and 35 (9%) cisplatin plus etoposide. Overall, 340/548 patients (62%) received maintenance immunotherapy. Most patients (68%) did not receive radiotherapy or PCI. CONCLUSIONS: There is an overall alignment of practices reflecting recent clinical guidelines among medical centers managing ES-SCLC across France, and a high prescription rate of immunotherapy in the first-line setting.

Tuning spatially fractionated radiotherapy dose profiles using the moiré effect.

Spatially Fractionated Radiotherapy (SFRT) has demonstrated promising potential in cancer treatment, combining the advantages of reduced post-radiation effects and enhanced local control rates. Within this paradigm, proton minibeam radiotherapy (pMBRT) was suggested as a new treatment modality, possibly producing superior normal tissue sparing to conventional proton therapy, leading to improvements in patient outcomes. However, an effective and convenient beam generation method for pMBRT, capable of implementing various optimum dose profiles, is essential for its real-world application. Our study investigates the potential of utilizing the moiré effect in a dual collimator system (DCS) to generate pMBRT dose profiles with the flexibility to modify the center-to-center distance (CTC) of the dose distribution in a technically simple way.We employ the Geant4 Monte Carlo simulations tool to demonstrate that the angle between the two collimators of a DCS can significantly impact the dose profile. Varying the DCS angle from 10 ∘ to 50 ∘ we could cover CTC ranging from 11.8 mm to 2.4 mm, respectively. Further investigations reveal the substantial influence of the multi-slit collimator's (MSC) physical parameters on the spatially fractionated dose profile, such as period (CTC), throughput, and spacing between MSCs. These findings highlight opportunities for precision dose profile adjustments tailored to specific clinical scenarios.The DCS capacity for rapid angle adjustments during the energy transition stages of a spot scanning system can facilitate dynamic alterations in the irradiation profile, enhancing dose contrast in normal tissues. Furthermore, its unique attribute of spatially fractionated doses in both lateral directions could potentially improve normal tissue sparing by minimizing irradiated volume. Beyond the realm of pMBRT, the dual MSC system exhibits remarkable versatility, showing compatibility with different types of beams (X-rays and electrons) and applicability across various SFRT modalities.Our study illuminates the dual MSC system's potential as an efficient and adaptable tool in the refinement of pMBRT techniques. By enabling meticulous control over irradiation profiles, this system may expedite advancements in clinical and experimental applications, thereby contributing to the evolution of SFRT strategies.

A nationwide phase II study of delayed local treatment for children with high-risk neuroblastoma: The Japan Children's Cancer Group Neuroblastoma Committee Trial JN-H-11.

PURPOSE: Survival rates of patients with high-risk neuroblastoma are unacceptable. A time-intensified treatment strategy with delayed local treatment to control systemic diseases has been developed in Japan. We conducted a nationwide, prospective, single-arm clinical trial with delayed local treatment. This study evaluated the safety and efficacy of delayed surgery to increase treatment intensity. PATIENTS AND METHODS: Seventy-five patients with high-risk neuroblastoma were enrolled in this study between May 2011 and September 2015. Delayed local treatment consisted of five courses of induction chemotherapy (cisplatin, pirarubicin, vincristine, and cyclophosphamide) and myeloablative high-dose chemotherapy (melphalan, etoposide, and carboplatin), followed by local tumor extirpation with surgery and irradiation. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), response rate, adverse events, and surgical complications. RESULTS: Seventy-five patients were enrolled, and 64 were evaluable (stage 3, n = 8; stage 4, n = 56). The estimated 3-year PFS and OS rates (95% confidence interval [CI]) were 44.4% [31.8%-56.3%] and 80.7% [68.5%-88.5%], resspectively. The response rate of INRC after completion of the treatment protocol was 66% (42/64; 95% CI: 53%-77%; 23 CR [complete response], 10 VGPR [very good partial response], and nine PR [partial response]). None of the patients died during the protocol treatment or within 30 days of completion. Grade 4 adverse effects, excluding hematological adverse effects, occurred in 48% of patients [31/64; 95% CI: 36%-61%]. Major Surgical complications were observed in 25% of patients [13/51; 95% CI: 14%-40%]. CONCLUSION: This study indicates that delayed local treatment is feasible and shows promising efficacy, suggesting that this treatment should be considered further in a comparative study of high-risk neuroblastoma.

Six versus four or five cycles of first-line etoposide and platinum-based chemotherapy combined with thoracic radiotherapy in patients with limited-stage small-cell lung cancer: A propensity score-matched analysis of a prospective randomized trial.

OBJECTIVES: The recommended treatment for limited-stage small-cell lung cancer (LS-SCLC) is a combination of thoracic radiotherapy (TRT) and etoposide plus cisplatin (EP) chemotherapy, typically administered over 4-6 cycles. Nonetheless, the optimal duration of chemotherapy is still not determined. This study aimed to compare the outcomes of patients with LS-SCLC who received either 6 cycles or 4-5 cycles of EP chemotherapy combined with TRT. MATERIALS AND METHODS: In this retrospective analysis, we utilized data from our prior prospective trial to analyze the outcomes of 265 LS-SCLC patients who received 4-6 courses of EP combined with concurrent accelerated hyperfractionated TRT between 2002 and 2017. Patients were categorized into two groups depending on their number of chemotherapy cycles: 6 or 4-5 cycles. To assess overall survival (OS) and progression-free survival (PFS), we employed the Kaplan-Meier method after conducting propensity score matching (PSM). RESULTS: Among the 265 LS-SCLC patients, 60 (22.6%) received 6 cycles of EP chemotherapy, while 205 (77.4%) underwent 4-5 cycles. Following PSM (53 patients for each group), the patients in the 6 cycles group exhibited a significant improvement in OS and PFS in comparison to those in the 4-5 cycles group [median OS: 29.8 months (95% confidence interval [CI], 23.6-53.1 months) vs. 22.7 months (95% CI, 20.8-29.1 months), respectively, p = 0.019; median PFS: 17.9 months (95% CI, 13.7-30.5 months) vs. 12.0 months (95% CI, 9.8-14.2 months), respectively, p = 0.006]. The two-year and five-year OS rates were 60.38% and 29.87% in the 6 cycles group, whereas 47.17% and 15.72% in the 4-5 cycles group, respectively. CONCLUSION: Patients diagnosed with LS-SCLC who were treated with EP regimen chemotherapy combined with TRT exhibited notably enhanced survival when administered 6 cycles of chemotherapy, as compared to those who underwent only 4-5 cycles.

Real-life study on the use of response adapted therapy in patients with Hodgkin Lymphoma: Results from a multicenter experience.

Few data are known regarding the use of interim positron emission tomography (iPET) after the first two cycles (iPET2) of chemotherapy in treatment-naïve classical Hodgkin lymphoma (cHL) in routine clinical practice, and about the real-life adoption of intensification strategies for iPET positive patients. We conducted a multicenter retrospective study on cHL to investigate the use of iPET in the real-life setting, its prognostic role and outcomes of patients early shifted to intensification. Six hundreds and forty-one patients were enrolled (62% had advanced stage). iPET2 was positive in 89 patients (14%) including 8.7% and 17% early and advanced stage patients, respectively (p = 0.003). Among iPET 2 positive cases treatment was immediately modified in 19 cases; in 14 cases treatment was modified after an additional positive iPET4. Overall 56 iPET2 positive patients never received intensified therapies. Most frequently used intensified therapy was autologous stem cell transplantation followed by BEACOPP. After a median follow-up of 72 months, the 5-year progression-free survival (PFS) was 82% with iPET2 positive patients showing a worse PFS compared with iPET2 negative cases: 31% versus 85%. Focusing on advanced stage patients with a positive iPET2, the 5-year PFS was 59% for patients shifted to intensified therapy at any time point versus 61% for patients who never received intensified therapy. Our study confirmed the higher curability of naïve cHL patients in a real-world setting, and the prognostic role of iPET2 in this setting. A poor adherence to response-adapted strategy which however did not translate into a difference in patient outcomes.

2,4-dinitrophenol enhances cisplatin and etoposide cytotoxic activity on prostate cancer cell line.

INTRODUCTION AND OBJECTIVE: Including additional compounds that disturb the energy metabolism of cancer cells in advanced cancer therapy regimens may be an approach to overcome the problem of drug resistance and the therapeutic effectiveness of classic chemotherapeutics. One of the compounds that decouple oxidative phosphorylation, and thus alter the activity of energy-producing pathways, is 2,4-DNP (2,4- dinitrophenol). OBJECTIVE: The aim of the study was to assess the ability of the 2,4-DNP to sensitize prostate cancer cells to the action of cisplatin and etoposide, or to intensify their action. MATERIAL AND METHODS: The research was carried out on three prostate cancer cell lines (LNCaP, PC-3, DU-145. To assess the effect of cisplatin or etoposide with 2,4-DNP on prostate cancer cells, MTT assay, analysis of the cell cycle and apoptosis detection was performed. Oxidative stress was investigated by CellRox fluorescence staining and expression of genes related to antioxidant defence. In addition, analysis was conducted of the expression of genes related to cell cycle inhibition, transporters associated with multi-drug resistance and DNA repair. RESULTS: The study showed that the simultaneous incubation of 2,4-DNP with cisplatin or etoposide enhances the cytotoxic effect of the chemotherapeutic agent only in LNCaP cells (oxidative phenotype). CONCLUSIONS: The enhanced cytotoxic effect of chemotherapeutics by 2,4-DNP may be the result of disturbed redox balance, reduced ability of cells to repair DNA, and the oxidative metabolic phenotype of prostate cancer cells.

Efficacy and safety of mitoxantrone, etoposide, and cytarabine for treatment of relapsed or refractory acute myeloid leukemia.

BACKGROUND/RATIONALE: Most patients with acute myeloid leukemia (AML) develop relapsed or refractory (R/R) disease after receiving initial induction chemotherapy. Salvage chemotherapy followed by allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only curative therapy for R/R AML. Mitoxantrone, etoposide, and cytarabine (MEC) is the current standard of care salvage regimen for R/R AML at Cleveland Clinic. The primary objective was to determine the overall remission rate (ORR: defined as patients achieving complete remission (CR) or complete remission with incomplete hematologic recovery (CRi)) in R/R AML patients who received MEC. METHODS: Adult patients with R/R AML treated with MEC between July 1, 2014 and September 30, 2022 were included. ORR and its association with baseline characteristics were determined. Secondary outcomes included overall survival (OS), event-free survival (EFS), relapse-free survival (RFS), and safety. RESULTS: Sixty patients were evaluated. The ORR was 51.7% (33.3% CR and 18.3% CRi). The median time from receipt of MEC to CR/CRi was 7.7 weeks. Patients with bone marrow blasts ≤20% and peripheral blood blasts ≤30% at MEC initiation were more than twice as likely to achieve CR/CRi compared to those with a higher blast burden. The median OS was 6.3 months. Twenty-four (40.0%) patients proceeded to alloHSCT. Twenty-one (35.0%) patients were transferred to the intensive care unit (ICU) during their admission. CONCLUSIONS: MEC is an effective salvage regimen for patients with R/R AML, especially among those with low disease burden at initiation. Febrile neutropenia, infections, and severe oral mucositis were common with MEC administration.

Role of CD38 in anti-tumor immunity of small cell lung cancer.

Introduction: Immune checkpoint blockade (ICB) with or without chemotherapy has a very modest benefit in patients with small cell lung cancer (SCLC). SCLC tumors are characterized by high tumor mutation burden (TMB) and low PD-L1 expression. Therefore, TMB and PD-L1 do not serve as biomarkers of ICB response in SCLC. CD38, a transmembrane glycoprotein, mediates immunosuppression in non-small cell lung cancer (NSCLC). In this brief report, we highlight the potential role of CD38 as a probable biomarker of immunotherapy response in SCLC. Methods: We evaluated the role of CD38 as a determinant of tumor immune microenvironment in SCLC with bulk and single-cell transcriptomic analyses and protein assessments of clinical samples and preclinical models, including CD38 in vivo blockade. Results: In SCLC clinical samples, CD38 levels were significantly correlated with the gene expression of the immunosuppressive markers FOXP3, PD-1 and CTLA-4. CD38 expression was significantly enhanced after chemotherapy and ICB treatment in SCLC preclinical models and clinical samples. A combination of cisplatin/etoposide, ICB, and CD38 blockade delayed tumor growth compared to cisplatin/etoposide. Conclusion: Our study provides a preliminary but important direction toward exploring CD38 as a potential biomarker of ICB response and CD38 blockade as a combination strategy for chemo-immunotherapy in SCLC.

An assessment and characterization of pharmaceuticals and personal care products (PPCPs) within the Great Lakes Basin: Mussel Watch Program (2013-2018).

Defining the environmental occurrence and distribution of chemicals of emerging concern (CECs), including pharmaceuticals and personal care products (PPCPs) in coastal aquatic systems, is often difficult and complex. In this study, 70 compounds representing several classes of pharmaceuticals, including antibiotics, anti-inflammatories, insect repellant, antibacterial, antidepressants, chemotherapy drugs, and X-ray contrast media compounds, were found in dreissenid mussel (zebra/quagga; Dreissena spp.) tissue samples. Overall concentration and detection frequencies varied significantly among sampling locations, site land-use categories, and sites sampled proximate and downstream of point source discharge. Verapamil, triclocarban, etoposide, citalopram, diphenhydramine, sertraline, amitriptyline, and DEET (N,N-diethyl-meta-toluamide) comprised the most ubiquitous PPCPs (> 50%) detected in dreissenid mussels. Among those compounds quantified in mussel tissue, sertraline, metformin, methylprednisolone, hydrocortisone, 1,7-dimethylxanthine, theophylline, zidovudine, prednisone, clonidine, 2-hydroxy-ibuprofen, iopamidol, and melphalan were detected at concentrations up to 475 ng/g (wet weight). Antihypertensives, antibiotics, and antidepressants accounted for the majority of the compounds quantified in mussel tissue. The results showed that PPCPs quantified in dreissenid mussels are occurring as complex mixtures, with 4 to 28 compounds detected at one or more sampling locations. The magnitude and composition of PPCPs detected were highest for sites not influenced by either WWTP or CSO discharge (i.e., non-WWTPs), strongly supporting non-point sources as important drivers and pathways for PPCPs detected in this study. As these compounds are detected at inshore and offshore locations, the findings of this study indicate that their persistence and potential risks are largely unknown, thus warranting further assessment and prioritization of these emerging contaminants in the Great Lakes Basin.

Preparation of etoposide liposomes for enhancing antitumor efficacy on small cell lung cancer and reducing hematotoxicity of drugs.

Etoposide (VP16) is commonly used in the treatment of small cell lung cancer (SCLC) in clinical practice. However, severe adverse reactions such as bone marrow suppression toxicity limit its clinical application. Although several studies on VP16 liposomes were reported, no significant improvement in bone marrow suppression toxicity has been found, and there was a lack of validation of animal models for in vivo antitumor effects. Therefore, we attempted to develop a PEGylated liposomal formulation that effectively encapsulated VP16 (VP16-LPs) and evaluated its therapeutic effect and toxicity at the cellular level and in animal models. First, we optimized the preparation process of VP16-LPs using an orthogonal experimental design and further prepared them into freeze-dried powder to improve storage stability of the product. Results showed that VP16-LPs freeze-dried powder exhibited good dispersibility and stability after redispersion. In addition, compared to marketed VP16 injection, VP16-LPs exhibited sustained drug release characteristics. At the cellular level, VP16-LPs enhanced the cellular uptake of drugs and exhibited strong cytotoxic activity. In animal models, VP16-LPs could target and aggregate in tumors and exhibit a higher anti-tumor effect than VP16-injection after intravenous injection. Most importantly, hematological analysis results showed that VP16-LPs significantly alleviated the bone marrow suppression toxicity of drug. In summary, our study confirmed that PEGylated liposomes could enhance therapeutic efficacy and reduce toxicity of VP16, which demonstrated that VP16-LPs had enormous clinical application potential.

Using the gamma-index analysis for inter-fractional comparison of in-beam PET images for head-and-neck treatment monitoring in proton therapy: A Monte Carlo simulation study.

GOAL: In-beam Positron Emission Tomography (PET) is a technique for in-vivo non-invasive treatment monitoring for proton therapy. To detect anatomical changes in patients with PET, various analysis methods exist, but their clinical interpretation is problematic. The goal of this work is to investigate whether the gamma-index analysis, widely used for dose comparisons, is an appropriate tool for comparing in-beam PET distributions. Focusing on a head-and-neck patient, we investigate whether the gamma-index map and the passing rate are sensitive to progressive anatomical changes. METHODS/MATERIALS: We simulated a treatment course of a proton therapy patient using FLUKA Monte Carlo simulations. Gradual emptying of the sinonasal cavity was modeled through a series of artificially modified CT scans. The in-beam PET activity distributions from three fields were evaluated, simulating a planar dual head geometry. We applied the 3D-gamma evaluation method to compare the PET images with a reference image without changes. Various tolerance criteria and parameters were tested, and results were compared to the CT-scans. RESULTS: Based on 210 MC simulations we identified appropriate parameters for the gamma-index analysis. Tolerance values of 3 mm/3% and 2 mm/2% were suited for comparison of simulated in-beam PET distributions. The gamma passing rate decreased with increasing volume change for all fields. CONCLUSION: The gamma-index analysis was found to be a useful tool for comparing simulated in-beam PET images, sensitive to sinonasal cavity emptying. Monitoring the gamma passing rate behavior over the treatment course is useful to detect anatomical changes occurring during the treatment course.

Physical compatibility of Xuebijing injection with 53 intravenous drugs during simulated Y-site administration.

OBJECTIVE: Xuebijing injection (XBJ) is a commonly used herbal medicine injection in China. However, the physical compatibility of XBJ with other intravenous drugs remains unclear. The purpose of this research is to evaluate physical compatibility of Xuebijing injection (XBJ) with 53 intravenous drugs (including 31 Chinese medicine injections and 22 chemicals) during simulated Y-site administration. METHODS: Y-site administration was simulated in vitro by admixing 0.33 ml/ml XBJ with an equal volume of other diluted 53 intravenous drugs, respectively. Physical compatibility including visual inspection, Tyndall beam, particle limits, turbidity, pH, chromacity value, spectroscopic absorption of 550 nm and 420 nm (A550 nm and A420 nm) were observed and assessed at 0, 1, 2, and 4 h. Physical compatibility was defined as all solutions with no color changes, no gas evolution, particulate formation and no Tyndall beam within 4 hours, turbidity changes <0.5 nephelometric turbidity unit (NTU) compared to 0 h, particle limits allowed by the Chinese Pharmacopoeia (Ch.P) 2020 edition, pH changes <10% compared to 0, chromacity value changes <200 compared to 0 h, or photometrical changes of A420 nm <0.0400 or A550 nm <0.0100 compared to 0 h. RESULTS: XBJ was physically incompatible with 27 of the 53 intravenous drugs tested, 26 were compatible with XBJ for 4 h. CONCLUSIONS: XBJ should not be simultaneously co-administered with 27 of the 53 intravenous drugs during simulated Y-site. If coadministration was inevitable, flushing tube with NS or D5W before and after infusion of XBJ was needed. Assessment included visual inspection, Tyndall beam, turbidity measurement, particle counts, pH measurement, chromacity value measurement and absorption of A550 nm were proved to be valid and robust for the quality control of infusion and compatibility of Chinese herbal injection.

Phase III, multicenter, randomized trial of 45 Gy versus 30 Gy thoracic radiation for extensive-stage small cell lung cancer (ES-SCLC): Study protocol.

BACKGROUND: Consolidative thoracic radiotherapy (cTRT) has previously shown benefit to patients with extensive stage small cell lung cancer (ES-SCLC) who respond to chemotherapy. However, the optimum dose of cTRT is unknown. The purpose of this randomized trial is to compare the efficacy of 45 Gy in 15 fractions with 30 Gy in 10 fractions cTRT in ES-SCLC. METHODS: This phase III, multicenter, randomized trial is designed to evaluate the safety and efficacy of different cTRT dose in ES-SCLC. Eligible patients with pathologically confirmed ES-SCLC who responded to 4-6 cycles of etoposide plus cisplatin (EP) or carboplatin (EC) chemotherapy were randomized 1:1 to receive either 30 Gy in 10 fractions (standard dose) or 45 Gy in 15 fractions (high dose) cTRT. The primary endpoint is 2-year overall survival (OS). Secondary endpoints include 2-year progression-free survival (PFS), 2-year local control (LC) and treatment related toxicity as measured by adverse events according to the Common Terminology Criteria for Adverse Events (version 4.0). DISCUSSION: The present study is the first randomized phase III trial designed to evaluate the efficacy of higher versus lower dose cTRT in ES-SCLC, providing evidence for future clinical practice in prolonging survival of patients with ES-SCLC.

Prognostic significance of body mass index and serum albumin as the indicators of nutritional status in small cell lung cancer.

BACKGROUND: Body mass index (BMI) and serum albumin (ALB) level are long-established markers that reflect the nutritional status and eventually the prognosis of cancer patients. The objective of the study was to determine the clinical significance of these factors and specify their roles in outcomes compared with performance status (PS) and weight loss (WL), which are considered the most significant patient-related prognostic factors in small cell lung cancer (SCLC) treated with platinum-etoposide-based chemotherapy. METHODS: A total of 378 patients with SCLC were enrolled in the study and analyzed retrospectively. RESULTS: BMI values were similar by clinical stage, whereas the percentages of the patients with WL, low serum ALB, and particularly poor (≥2) PS were significantly higher in patients with extended disease SCLC (ED-SCLC) compared to those with limited disease SCLC (LD-SCLC). In LD-SCLC, patients with poor PS lived for a significantly shorter time than patients with good PS (HR: 7.791, p = 0.0001); however, BMI (HR: 1.035, p = 0.8), WL (HR: 0.857, p = 0.5), and ALB (HR: 0.743, p = 0.3) had no significant effect on the outcome. In ED-SCLC, PS (HR: 4.257, p = 0.0001), WL (HR: 1.677, p = 0.001), and ALB (HR: 0.680, p = 0.007) had an impact on survival, but BMI did not (HR: 0.791, p = 0.08). In LD-SCLC, the univariate analysis showed that only poor PS was correlated with increased mortality (HR: 7.791, p = 0.0001); yet it lost significance in multivariate analysis. In ED-SCLC, poor PS (HR: 4.257, p = 0.0001), WL (HR: 1.667, p = 0.001), and a low ALB level (HR: 0.680, p = 0.007) were shown to be factors for poor prognosis in the univariate analysis; yet only PS remained significant in multivariate analysis (HR: 2.286, p = 0.001). CONCLUSION: Even though BMI and serum albumin showed no prognostic value in SCLC patients treated with chemotherapy, PS was found to be the most significant prognostic factor in both LD- and ED-SCLC stages.

Three-row MRI receive array with remote circuitry to preserve radiation transparency.

Objective.Up to this point, 1.5 T linac-compatible coil array layouts have been restricted to one or two rows of coils because of the desire to place radiation-opaque circuitry adjacent to the coils and outside the window through which the linac beam travels. Such layouts can limit parallel imaging performance. The purpose of this work was to design and build a three-row array in which remotely located circuits permitted a central row of coils while preserving the radiolucent window.Approach.The remote circuits consisted of a phase shifter to cancel the phase introduced by the coaxial link between the circuit and coil, followed by standard components for tuning, matching, detuning, and preamplifier decoupling. Tests were performed to compare prototype single-channel coils with remote or local circuits, which were followed by tests comparing two and three-row arrays .Main results.The single-channel coil with the remote circuit maintained 85% SNR at depths of 30 mm or more as compared to a coil with local circuit. The three-row array provided similar SNR as the two-row array, along with geometry factor advantages for parallel imaging acceleration in the head-foot direction.Significance.The remote circuit strategy could potentially support future MR-linac arrays by allowing greater flexibility in array layout compared to those confined by local circuits, which can be leveraged for parallel imaging acceleration.

Methodology for small animals targeted irradiations at conventional and ultra-high dose rates 65 MeV proton beam.

As part of translational research projects, mice may be irradiated on radiobiology platforms such as the one at the ARRONAX cyclotron. Generally, these platforms do not feature an integrated imaging system. Moreover, in the context of ultra-high dose-rate radiotherapy (FLASH-RT), treatment planning should consider potential changes in the beam characteristics and internal movements in the animal. A patient-like set-up and methodology has been implemented to ensure target coverage during conformal irradiations of the brain, lungs and intestines. In addition, respiratory cycle amplitudes were quantified by fluoroscopic acquisitions on a mouse, to ensure organ coverage and to assess the impact of respiration during FLASH-RT using the 4D digital phantom MOBY. Furthermore, beam incidence direction was studied from mice µCBCT and Monte Carlo simulations. Finally,in vivodosimetry with dose-rate independent radiochromic films (OC-1) and their LET dependency were investigated. The immobilization system ensures that the animal is held in a safe and suitable position. The geometrical evaluation of organ coverage, after the addition of the margins around the organs, was satisfactory. Moreover, no measured differences were found between CONV and FLASH beams enabling a single model of the beamline for all planning studies. Finally, the LET-dependency of the OC-1 film was determined and experimentally verified with phantoms, as well as the feasibility of using these filmsin vivoto validate the targeting. The methodology developed ensures accurate and reproducible preclinical irradiations in CONV and FLASH-RT without in-room image guidance in terms of positioning, dose calculation andin vivodosimetry.