Limited Stage Research Articles

Stage at diagnosis and survival by stage for the leading childhood cancers in Rwanda.

The lack of accurate population-based information on childhood cancer stage and survival in low-income countries is a barrier to improving childhood cancer outcomes. In this study, data from the Rwanda National Cancer Registry (RNCR) were examined for children aged 0-14 diagnosed in 2013-2017 for the eight most commonly occurring childhood cancers: acute lymphoblastic leukaemia, Hodgkin lymphoma (HL), Burkitt lymphoma (BL), non-Hodgkin lymphoma excluding BL, retinoblastoma, Wilms tumour, osteosarcoma and rhabdomyosarcoma. Utilising the Toronto Childhood Cancer Stage Guidelines Tier 1, the study assigned stage at diagnosis to all, except HL, and conducted active follow-ups to calculate 1-, 3- and 5-year observed and relative survival by cancer type and stage at diagnosis. The cohort comprised 412 children, of whom 49% (n=202) died within 5years of diagnosis. Five-year survival ranged from 28% (95% confidence interval [CI]: 12.5%-45.6%) for BL to 68% (CI: 55%-78%) for retinoblastoma. For the cancers for which staging was carried out, it was assigned for 83% patients (n=301 of 362), with over half (58%) having limited or localised stage at diagnosis. Stage was a strong predictor of survival; for example, 3-year survival was 70% (95% CI: 45.1%-85.3%) and 11.8% (2.0%-31.2%) for limited and advanced non-HL, respectively (p<.001). This study is only the second to report on stage distribution and stage-specific survival for childhood cancers in sub-Saharan Africa. It demonstrates the feasibility of the Toronto Stage Guidelines in a low-resource setting, and highlights the value of population-based cancer registries in aiding our understanding of the poor outcomes experienced by this population.

Pengembangan Lembar Kerja Peserta Didik (LKPD) Berorientasi Problem Solving untuk Melatihkan Keterampilan Berpikir Kritis Peserta Didik pada Materi Asam Basa

The purpose of this research was to describe the viability of using problem solving worksheets to teach students how to think critically about acid-base material. In assessing the viability of the student worksheets that have been developed, there are three factors that are taken into consideration, namely validity, practicality, and efficacy. In this study, 22 students from class XI MIPA 13 SMAN 1 Sidoarjo participated in a limited trial stage of the Research and Development (R&amp;D) technique from Borg and Gall. The findings of this research indicate that validity, which comprises construct and content validity, each received a mode value of four using appropriate standards. Based on student reaction surveys, practicality reached 92.80% with extremely practical standards, and relevant student activities in the first and second meetings respectively obtained a percentage of 95 55% and 96.12%. The N-gain test yielded medium and high criteria for efficacy. The research's findings indicate that problem solving focused student worksheets are a workable way to support students in strengthening their capacity for critical thought when studying acid-base content.

Mobilizing endogenous neuroprotection: the mechanism of the protective effect of acupuncture on the brain after stroke.

Given its high morbidity, disability, and mortality rates, ischemic stroke (IS) is a severe disease posing a substantial public health threat. Although early thrombolytic therapy is effective in IS treatment, the limited time frame for its administration presents a formidable challenge. Upon occurrence, IS triggers an ischemic cascade response, inducing the brain to generate endogenous protective mechanisms against excitotoxicity and inflammation, among other pathological processes. Stroke patients often experience limited recovery stages. As a result, activating their innate self-protective capacity [endogenous brain protection (EBP)] is essential for neurological function recovery. Acupuncture has exhibited clinical efficacy in cerebral ischemic stroke (CIS) treatment by promoting the human body's self-preservation and "Zheng Qi" (a term in traditional Chinese medicine (TCM) describing positive capabilities such as self-immunity, self-recovery, and disease prevention). According to research, acupuncture can modulate astrocyte activity, decrease oxidative stress (OS), and protect neurons by inhibiting excitotoxicity, inflammation, and apoptosis via activating endogenous protective mechanisms within the brain. Furthermore, acupuncture was found to modulate microglia transformation, thereby reducing inflammation and autoimmune responses, as well as promoting blood flow restoration by regulating the vasculature or the blood-brain barrier (BBB). However, the precise mechanism underlying these processes remains unclear. Consequently, this review aims to shed light on the potential acupuncture-induced endogenous neuroprotective mechanisms by critically examining experimental evidence on the preventive and therapeutic effects exerted by acupuncture on CIS. This review offers a theoretical foundation for acupuncture-based stroke treatment.

Small Cell Lung Cancer in Norway: Patterns of Care by Health Region and Survival Trends

Introduction/BackgroundThere has been a marked survival improvement for patients with non–small-cell lung cancer. We describe the national trends in characteristics and survival, and geographical differences in diagnostic workup, treatment, and survival for patients with small-cell lung cancer (SCLC). Materials and MethodsPatients registered with SCLC at the Cancer Registry of Norway in 2002 to 2022 were included. Trends in overall survival were estimated for all SCLC patients, patients with limited stage SCLC, patients undergoing surgery, and by health region. Adjusting for case-mix, a multivariable Cox regression was performed examining the association between health region and death. ResultsThe study included 8374 patients. The stage distribution remained unchanged during the study period. The 5-year overall survival increased from 7.7% to 22.8% for patients with limited stage. The use of multidisciplinary team meetings varied from 62.5% to 85.7%, and the use of positron emission tomography-computer tomography varied from 70.4% to 86.2% between the health regions. Treatment patterns differed markedly between the health regions, with the proportion dying without any registered treatment ranging from 1.2% to 10.9%. For limited stage patients in 2018 to 2022, the median overall survival ranged from 16.5 to 25.5 months across health regions, and the 5-year overall survival ranged from 18.7% to 28.7% (P = .019). ConclusionThe survival for patients with SCLC remains poor. The use of diagnostic procedures, treatment modalities, and survival differed between regions, warranting investigations to further explore the reasons.

Evaluation of Radiation Therapy Treatment Plans in a Randomized Phase 2 Trial Comparing 2 Schedules of Twice-Daily Thoracic Radiation Therapy in Limited Stage Small Cell Lung Cancer

PurposeThere is limited clinical data for recommendations on how to deliver thoracic radiotherapy (TRT) concurrently with chemotherapy in limited stage (LS) small-cell lung cancer (SCLC). We reviewed radiotherapy treatment plans in a randomized phase II trial comparing high-dose with standard-dose twice-daily TRT to assess treatment planning techniques, dose-volume data for target volumes and organs at risk (OARs), evaluate compliance with the protocol, associations with radiation-induced toxicity and whether an imbalance in treatment planning parameters might be a reason for the large survival benefit of the higher dose (median overall survival 43.6 vs. 22.6 months). Methods and Materials170 patients were to receive four courses of platinum/etoposide and randomized to receive twice-daily TRT of 60 Gy/40 fractions (fx) or 45 Gy/30 fx. TRT treatment plans for those who received one or more fx of TRT (n=166) were analyzed. ResultsThe most common treatment planning technique was 3DCRT (67%). The 75th percentile of the reported dose-volume parameters for the OARs were within the protocol-recommended limits for both groups. Mean doses to the esophagus of 25.5 Gy (IQR: 20.2-31.3) [60 Gy/40 fx] and 24.3 Gy (IQR: 20.3-27.5) [45 Gy/30 fx] were associated with 21% and 18% ≥ grade 3 acute esophagitis, respectively. In the 60 Gy/40 fx group, a mean dose to the lungs of 16.5 Gy (IQR: 15.8-16.9), V20Gy of 29.5% (IQR: 28.8-30.4), and V5Gy of 65.6% (IQR: 61.5-68.7) led to ≥ grade 3 pneumonitis in 4% of the patients. There was no ≥ grade 3 pneumonitis in the 45 Gy group. Treatment planning techniques, the percentage change in volumes between original and re-delineated OARs, PTV volumes, relative doses, and laterality were well balanced between the randomly assigned groups. ConclusionConsidering that the incidences of severe radiation-induced toxicities were within the range of other recent trials, the reported doses to the OARs appear to be safe. Treatment planning parameters were well balanced between the randomly assigned groups, supporting that the survival benefit of the twice-daily 60 Gy/ 40 fx TRT schedule was due to the higher dose.

Abstract 1125: TNIK induced chemoradiation resistance in small cell lung cancer

Abstract Chemoradiation (CRT) is the standard first-line therapy for limited stage small cell lung cancer (LS-SCLC), which is characterized by early metastasis, intrinsic-acquired CRT resistance and tumor recurrence. CRT confers a 20-25% 5-year overall survival in patients with LS-SCLC. In this study, we utilized patient-derived xenograft (PDX) models to demonstrate CRT resistance of SCLC and identified CRT resistance candidate genes from various SCLC PDX that represent the majority of molecular subtypes (n=4 that include SCLC-A and SCLC-N subtypes). RNA-seq data identified TNIK (Traf2- and Nck-interacting kinase) as one such gene that is consistently upregulated in SCLC PDXs exposed to CRT compared to single modality treatments. Copy number gains of TNIK were also present in human SCLC samples. Overcoming this CRT resistance is crucial in improving treatment outcomes and patient survival. Genetic depletion or pharmacological inhibition of TNIK reduced the in vitro clonogenic survival of TNIKhigh SCLC cells, NCI-H446 and makes them increasingly sensitive to CRT. In vivo, pharmacological inhibition of TNIK with the inhibitor NCB-0846, enhances the CRT sensitivity of NCI-H446 cell line-derived xenografts (CDX) in NOD SCID immunodeficient mice. Furthermore, pharmacological inhibition of TNIK in vivo demonstrated sensitivity to CRT in LX33 PDX. In conclusion, our results indicate that TNIK plays a role in conferring resistance to CRT in vitro in SCLC cell lines and in vivo in SCLC CDX and PDX models and therefore, can be a potential therapeutic target in limited stage SCLC. Citation Format: Dipanwita Dutta Chowdhury, Eddie Imada, Nick Connis, Triet Nguyen, Jinhee Chang, Danielle Council, Audrey Lafargue, Mohammad Rezaee, Phuoc T. Tran, Luigi Marchionni, Christine L. Hann. TNIK induced chemoradiation resistance in small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1125.

Prognostic value of PAX8 in small cell lung cancer

ObjectivesSmall cell lung cancer (SCLC) shows poor prognosis since it metastasizes widely at early stage. Paired box gene (PAX) 8 is a transcriptional factor of PAX family, of which the expression in lung cancer is a controversial issue, and its prognostic value of PAX8 in SCLC is still unclear. Materials and methodsOverall, 184 subjects who were pathologically diagnosed with SCLC were enrolled in the study. Immunohistochemical analysis of PAX8 and Ki-67 were performed. The correlations between PAX8 expression and clinical features or Ki-67 index were further analyzed. Subsequently, an analysis of the association between PAX8, stage, Ki-67 status, and overall survival (OS) were performed in 169 subjects with follow-up information. ResultsPAX8 was positive in 53.8% (99/184) SCLC specimens. The positive rate is significantly higher in extensive-stage specimens (61.0%) than in limited-stage specimens (45.24%). PAX8 expression is positively correlated with Ki-67 index (P = 0.001) while negatively correlated with OS (HR = 3.725, 95% CI 1.943–7.139, P＜0.001). In combination groups, the PAX8 negative and limited stage group had the most promising OS. ConclusionPAX8 expression rate in SCLC specimens is not low. It has prognostic value in small cell lung cancer.

Long-Term Outcomes After Concurrent Once- or Twice-Daily Chemoradiation in Limited-Stage Small Cell Lung Cancer: A Brief Report From the CONVERT Trial

CONVERT was a phase 3 international randomized clinical trial comparing once-daily (OD) and twice-daily (BD) radiation therapy (RT). This updated analysis describes the 6.5-year outcomes of these regimens delivered with conformal techniques. CONVERT (NCT00433563) randomized patients 1:1 between OD RT (66 Gy/33 fractions/6.5 weeks) and BD RT (45 Gy/30 fractions/3 weeks), both delivered with concurrent cisplatin/etoposide. Three-dimensional conformal RT was mandatory, intensity-modulated RT was permitted, and elective nodal irradiation was not allowed. Prophylactic cranial irradiation was delivered at the discretion of treating clinicians. RT treatment planning was subject to central quality assurance. Five hundred forty-seven patients were recruited at 73 centers. The median follow-up for the surviving cohort (n = 164) was 81.2 months. The median survival for the OD and BD arms were 25.4 months (95% CI, 21.1-30.9) and 30.0 months (95% CI, 25.3-36.5; hazard ratio, 1.13; 95% CI, 0.92-1.38; P = .247). Performance status and tumor volume were associated with survival on multivariate analysis. No treatment-related deaths occurred subsequent to the initial analysis performed in 2017. Regarding late toxicity, 7 patients in the OD arm developed grade 3 esophagitis, 4 of which went on to develop stricture or fistulation, compared with no patients in the BD arm. Grade 3 pulmonary fibrosis occurred in 2 and 3 patients in the OD and BD arms, respectively. As the CONVERT trial did not demonstrate the superiority of OD RT and this regimen had a slightly worse toxicity profile after 80 months of follow-up, 45 Gy BD should remain the standard of care in limited stage small cell lung cancer.

Features of using ozone for cleaning marine pollution

The subject of the research is issues related to the field of ship power plants and their elements, as well as the operation of water transport and its environmental safety. Studying the processes of ballast water purification and disinfection, as well as oil-containing water that are formed during the ships operation, shows the possibility of increasing the efficiency of these processes. It is proposed to consider these processes, starting from the stage of supplying the ozone-air mixture to the flow of treated water, without limiting ourselves to the study of the actual process of oxidation by ozone of a contaminated, including bacteriologically hazardous, substance. This approach makes it possible to establish the limiting stages of the contaminated water purification and disinfection process, which includes the stage of ozone dissolution in water during its transition from the ozone-air mixture, as well as the stage of subsequent diffusion of ozone dissolved in water into the reaction contact zone. It has been shown that the kinetic characteristics of the limiting stages depend on the conditions of their implementation, which can reduce the efficiency of ozone use due to the limited time of its existence. A technological proposal that makes it possible to increase the efficiency of ozone use and the reliability of ensuring the requirements for the quality of cleaning and disinfection of marine pollution has been developed. Technological proposals provide for the preliminary saturation with ozone of a specially allocated water stream for this purpose, the supply of this stream to the concentration zone of the oxidized and disinfected substance. A device in which the developed technological fragment, including a pump supplying a water flow to a contact column, an ozone generator, a device for supplying an ozone-saturated water flow to a filter, is implemented is also proposed.

Predicting overall survival and prophylactic cranial irradiation benefit in small-cell lung cancer with CT-based deep learning: A retrospective multicenter study

Background and purposeTo develop a computed tomography (CT)-based deep learning model to predict overall survival (OS) among small-cell lung cancer (SCLC) patients and identify patients who could benefit from prophylactic cranial irradiation (PCI) based on OS signature risk stratification. Materials and methodsThis study retrospectively included 556 SCLC patients from three medical centers. The training, internal validation, and external validation cohorts comprised 309, 133, and 114 patients, respectively. The OS signature was built using a unified fully connected neural network. A deep learning model was developed based on the OS signature. Clinical and combined models were developed and compared with a deep learning model. Additionally, the benefits of PCI were evaluated after stratification using an OS signature. ResultsWithin the internal and external validation cohorts, the deep learning model (concordance index [C-index] 0.745, 0.733) was far superior to the clinical model (C-index: 0.635, 0.630) in predicting OS, but slightly worse than the combined model (C-index: 0.771, 0.770). Additionally, the deep learning model had excellent calibration, clinical usefulness, and improved accuracy in classifying survival outcomes. Remarkably, patients at high risk had a survival benefit from PCI in both the limited and extensive stages (all P < 0.05), whereas no significant association was observed in patients at low risk. ConclusionsThe CT-based deep learning model exhibited promising performance in predicting the OS of SCLC patients. The OS signature may aid in individualized treatment planning to select patients who may benefit from PCI.

216TiP A phase II study of consolidation serplulimab following hypofractionated radiotherapy with concurrent chemotherapy for patients with limited stage small cell lung cancer (ASTRUM-LC01)

216TiP A phase II study of consolidation serplulimab following hypofractionated radiotherapy with concurrent chemotherapy for patients with limited stage small cell lung cancer (ASTRUM-LC01)

CD14-CD10-CD45+HLA-DR-SSC+ neutrophils may be granulocytic myeloid-derived suppressor cell-like cells and relate to disease progression in non-Hodgkin's lymphoma patients.

We explored the frequency of CD14-CD10-CD45+HLA-DR-SSC++ neutrophils (CD10- neutrophils) in patients with non-Hodgkin's lymphoma (NHL), and their immunologic characteristics and clinical significance. Patients with NHL who were newly diagnosed (NDP; n = 33), in remission (RMP; n = 28) and relapsed (RLP; n = 29) were included, and 47 volunteers were recruited as healthy controls (HCs). The frequency of CD10- neutrophils in the peripheral blood from HC and patients with NHL was detected. CD10- and CD10+ neutrophils were sorted, and their cytology was analyzed. CD3+ T cells were also isolated and cultured with the autologous CD10- or CD10+ neutrophils, after which the proliferation and death rates of T cells were determined. The levels of arginase-1 (Arg-1) and reactive oxygen species (ROS) in CD10+ or CD10- neutrophils were examined. Few CD10- neutrophils were detected in HCs but were significantly elevated in patients with NHL, especially in NDP and RLP. In addition, CD10- neutrophils in NDP with advanced stage and high risk were markedly higher than those in NDP with limited stage and low risk. In RMP and RLP, the relapse-free survival and overall survival in patients with high CD10- neutrophils were shorter than those with low CD10- neutrophils. CD10- neutrophils from patients with NHL, which mainly consist of immature neutrophils, inhibit T-cell proliferation and facilitate T-cell death. Furthermore, a significant increase was observed in Arg-1 expression, along with an increase to a certain extent in ROS. CD10- neutrophils in patients with NHL have characteristics of myeloid-derived suppressor cells and may be related to disease progression and poor prognosis.

Safety, efficacy, and affordability of ABVD for Hodgkin lymphoma in Malawi: a prospective cohort study

ABVD (doxorubicin, bleomycin, vinblastine, and dexamethasone) is a proven, curative regimen for Hodgkin lymphoma (HL). Prospective data describing HL treatment in sub-Saharan Africa are limited. We aimed to fill this knowledge gap, using data from Malawi. We report a prospective observational cohort of HL (aged 15) from a single, tertiary referral centre in Malawi. We enrolled patients with pathologicially confirmed Hodgkin lymphoma between June 1, 2013, and Dec 31, 2021 with follow-up censored on May 31, 2022. Patients were treated with ABVD and concurrent antiretroviral therapy if HIV-positive and were followed up for 5 years. The primary outcome was overall survival; secondary outcomes included progression-free survival, response assessment, and adverse events. Microcosting of HL diagnosis, treatment, and follow-up was embedded. We enrolled 38 patients with a median age of 27 years (interquartile range 19-46); eleven (28%) were HIV-positive. Of 35 patients treated with ABVD, 24 (71%) had stage III/IV, nine (26%) unfavourable limited stage, and two (6%) favourable limited stage. Among HIV-infected individuals, mean CD4 count at HL diagnosis was 179cells/uL and ten (91%) had HIV RNA < 400 copies/mL. Grade 3/4 neutropenia occurred in 24 (68%) patients and caused treatment delay in 16 (46%). Of ten deaths, seven were due to HL, two possible treatment-related toxicity, and one uncertain. 2-year overall survival was 82% (95% CI 70-96%) and 2-year progression-free survival was 64% (95% CI 50-83%). PFS appeared better for HIV-positive patients (HR 0.23 (95% CI 0.05-1.02)) after controlling for stage and performance status (p=0.05). We estimated $2708 (2022 USD) for HL diagnosis, treatment, and follow-up in our cohort. Our findings suggest that treatment with ABVD is safe, efficacious, and affordable for HL in Malawi. Outcomes are worse than in high-income countries due to HL progression. Future studies are needed to understand outcome inequities and to assess efficacy of therapies for patients with relapsed or refractory HL in Malawi. National Institutes of Health, Lineberger Comprehensive Cancer Center.

A MYC-rearrangement is a negative prognostic factor in stage II, but not in stage I diffuse large B-cell lymphoma

MYC oncogene rearrangements (MYC-R) negatively affect survival in patients with Ann Arbor stage III–IV diffuse large B-cell lymphoma (DLBCL), but their impact in limited stage (LS) I–II is unclear. Therefore, we assessed the impact of MYC-R on progression-free survival (PFS) and overall survival (OS) in LS DLBCL patients at the population level. We identified 1,434 LS DLBCL patients with known MYC-R status diagnosed between 2014 and 2020, who received R-CHOP(-like) regimens using the Netherlands Cancer Registry, with survival follow-up until February 2022. Stage I patients with (n = 83, 11%) and without (n = 650, 89%) a MYC-R had similar 2-years PFS (89% and 93%, p = 0.63) and OS (both 95%, p = 0.22). Conversely, stage II DLBCL patients with a MYC-R (n = 90, 13%) had inferior survival outcomes compared to stage II patients without a MYC-R (n = 611, 87%) (PFS 70% vs. 89%, p = 0.001; OS 79% vs. 94%, p < 0.0001). Both single MYC-R (single hit, n = 36) and concurrent BCL2 and/or BCL6 rearrangements (double/triple hit, n = 39) were associated with increased mortality and relapse risk. In conclusion, in stage II DLBCL a MYC-R is negatively associated with survival. In stage I DLBCL, however, survival outcomes are excellent irrespective of MYC-R status. This challenges the diagnostic assessment of MYC-R in stage I DLBCL patients.

Clinical and pathological characteristics and prognosis analysis of gray zone lymphoma

To explore the clinical and pathological characteristics as well as therapies and prognosis of gray zone lymphoma (GZL). The clinical data of 10 GZL patients admitted to the First Affiliated Hospital of Soochow University from December 2016 to December 2022 were retrospectively collected. The clinical and pathological characteristics, therapies and prognosis were analyzed. The cut-off time for follow-up visits was December 31, 2022, and the median time for follow-up visits [M(Q1, Q3)] was 40.0 (28.3, 59.8) months. Treatment efficacy was divided into complete remission (CR), partial remission (PR), stable disease (SD) and progressive disease (PD). There were 6 males and 4 females, with a median age [M(Q1, Q3)] of 33.5 (27.3-39.5) years. Among them, 8 patients had mediastinal (thymus) involvement and 7 patients were accompanied with extranodal involvement. According to Ann Arbor staging, 1 case was in the limited stage and 9 cases were in the progressive stage. The immunophenotypes of 4 patients were strong expression of CD20, expression of CD30, and no expression of CD15. The immunophenotypes of 6 patients were unequal expression of CD20 and strong expression of CD30 and CD15. One patient received classical hodgkin lymphoma(cHL)-like immunochemotherapy and only achieved PR, and then received enhanced diffuse large b-cell lymphoma (DLBCL)-like immunochemotherapy to achieve CR. Five patients received enhanced DLBCL-like immunochemotherapy for induction therapy and achieved CR. All 4 patients who did not achieve CR achieved CR after receiving second-line or third-line salvage therapy. All patients were given autologous stem cell transplantation (ASCT) for consolidation therapy. One patient relapsed and died during the follow-up visit in the 33rd month, and the remaining patients currently maintained a state of sustained remission. It is found that GZL mostly occurs in young patients, mediastinal involvement is common, and diagnosis relies on pathological morphology and immunophenotype. GZL may be more sensitive to DLBCL-like intensive immune regimens. Sequential ASCT for consolidation can reduce the risk of relapse.

Clinical Value of Human Endogenous Retrovirus-H Long Terminal Repeat Associating 2 (HHLA2) in Small Cell Lung Cancer.

Objective: Human endogenous retrovirus-H long terminal repeat associating 2 (HHLA2) is a new immune checkpoint in the B7 family, and the value of HHLA2 in small cell lung cancer (SCLC) is unknown. Methods: We retrospectively detected HHLA2 expression by immunohistochemistry in SCLC patients. Moreover, plasma biomarkers of SCLC were detected retrospectively. Results: Seventy-four percent of SCLC patients exhibited HHLA2 expression. HHLA2 staining was localised within the nucleus of SCLC cells, while no staining was detected in normal lung tissue specimens. The correlation between HHLA2 expression and clinical factors was also analysed. Limited stage (LS) SCLC was more common than extensive stage (ES) SCLC among patients with HHLA2 staining. SCLC patients without metastasis had higher HHLA2 expression than SCLC patients with metastasis. HHLA2 expression was more frequently detected in the group with a tumour size greater than 5 cm than in the group with a tumour size less than 5 cm. The proportion of patients with HHLA2-positive staining was greater in the stage III and IV SCLC groups than in the stage I and II SCLC groups. A high proportion of SCLC patients with HHLA2-positive staining had a survival time <2 years. Neuron-specific enolase (NSE), CEA and Ki-67 levels were measured. The NSE level in the HHLA2-positive group was significantly greater than that in the HHLA2-negative group. The CEA and Ki-67 levels did not significantly differ between the HHLA2-positive and HHLA2-negative patients, nor were age, sex, smoking status, nodal metastasis status, Karnofsky Performance Scale (KPS) score, or Ki-67 expression score. HHLA2-positive SCLC patients had higher tumour stages and shorter 2-year survival times than HHLA2-negative patients did. Conclusion: The new immune molecule HHLA2 may be an ideal clinical biomarker for predicting SCLC progression and could serve as a new immunotherapy target in SCLC.

Measuring the Effectiveness of Guided Inquiry-Based Modules for Training Analytical Thinking Skills in Teaching Materials on the Structure and Function of Plant Tissues for Class VIII SMP Negeri 22 Surakarta

Research and development objectives: measure the effectiveness of analytical thinking skills through guided inquiry-based modules. Data analysis used during research and development is descriptive analysis, percentage techniques and anacova tests. Research and development of teaching modules uses the Borg Gall procedural model which has been modified into nine stages: 1) research and information gathering stage, 2) planning stage, 3) initial product design development stage, 4) initial field trial stage, 5) initial first stage product revision, 6) limited field test stage, 7) second stage product revision stage, 8) operational field test stage, 9) final product revision stage. The results of research and development show: the guided inquiry-based module is effective in training analytical thinking skills, because based on the results of the Anakova test, it shows that there are differences in post-test results between the experimental, control and model classes. teaching material on the structure and function of plant tissues with F Table (0.05) = 2.37 F Calculate (0.05: 2) = 6.35.

Development of Mathematics Teaching Material based on Experiential Learning Model to Improve Students’ Mathematical Literacy Skills

This study aims to determine the development of the process of mathematics teaching materials based on the Experiential Learning model to improve mathematical literacy skills in two-variable linear equation system materials as well as the level of validity, practicality, and effectiveness. This type of research is Research and Development regarding the ADDIE development model, which consists of several stages: Analysis, Design, Development, Implementation, and Evaluation. The product developed as teaching materials is a module based on the Experiential Learning model on the material of a two-variable linear equation system. The test subjects in this study were grade VIIIA students of SMPN 45 Makassar, totaling 28 students. The instruments used in this study were expert validation sheets, student response questionnaires, teacher response questionnaires, observation sheets of teacher ability in managing learning, observation sheets of student activities, and learning outcome tests. The results showed that in the limited trial stage, teaching materials based on experiential learning on two-variable linear equation system material had met the criteria of validity, practicality, and effectiveness.

Quantitative Analysis of Hydraulic Fracturing Test Site 2 Completion Designs Using Crosswell Strain Measurement

Summary The implementation of effective completion design configurations during hydraulic stimulation is critical for the economic development of unconventional reservoirs. Low-frequency distributed acoustic sensing (LF-DAS)-based crosswell strain measurement is an advanced monitoring technique used to diagnose completion design efficiency but has been primarily restricted to qualitative analysis. In this study, we apply our novel Green-function based inversion algorithm to calculate fracture geometry (i.e., width) using the Department of Energy sponsored Hydraulic Fracturing Test Site 2 (HFTS-2) data set. The adopted algorithm relies on a 3D displacement discontinuity method to construct geomechanical models inverting linear elastic strain to hydraulic fracture widths. We use the inversion algorithm to calculate dynamic fracture widths using LF-DAS data recorded at two horizontal monitoring wells with permanent optical fiber installations. The inverted fracture widths at the monitoring wells from more than 100 hydraulic fracturing stages are used to diagnose the efficiency of eight unique completion designs implemented across three fracturing wells. We develop several metrics to evaluate completion design efficiency including the evenness of fracture widths at the monitoring wells, fracture density (i.e., number of fracture hits per foot), and fracture-width-density (i.e., fracture width/stage length). We observe a significant impact on completion efficiency with varying degrees of limited entry, tapered configurations, and stage length designs. Results indicate improved hydraulic stimulation is achieved with the implementation of limited-entry designs for extended stage lengths (ESLs), but no observable trend for normal stage lengths (NSLs). Tapered configurations significantly improve efficiency for ESLs but indicate little impact on normal-length designs. Reducing the space between perforation clusters (PCs) is determined to negatively impact design performance. Additionally, our quantitative analysis describes the impact of the nearby depletion zone on completion design efficiency. The methodology developed in this study provides operators with another level of quantitative information to optimize hydraulic fracturing treatments and reduce costs associated with the development of unconventional wells.

Re-examining prophylactic cranial irradiation in small cell lung cancer: a systematic review and meta-analysis

Patients with small cell lung cancer (SCLC) are at high risk for brain metastases. Prophylactic cranial irradiation (PCI) is recommended in this population to reduce the incidence of brain metastases and prolong survival. We aimed to assesses the efficacy of PCI in this population in the era of routine brain imaging. To our knowledge, this is the first systematic review and meta-analysis to examine the use among patients who were radiographically confirmed not to have brain metastases after completion of first-line therapy. In this systematic review and meta-analysis, cohort studies and controlled trials reporting on the use of PCI for patients SCLC were identified in EMBASE, MEDLINE, CENTRAL, and grey literature sources. The literature search was conducted on November 12, 2023. Summary data were extracted. Random-effects meta-analyses pooled hazard ratios (HR) for the primary outcome of overall survival between PCI and no intervention groups. This study is registered with the Open Science Framework, DOI:10.17605/OSF.IO/BC359, and PROSPERO, CRD42021249466. Of 4318 identified records, 223 were eligible for inclusion. 109 reported on overall survival in formats amenable to meta-analysis; PCI was associated with longer survival in all patients with SCLC (HR 0.59; 95% CI, 0.55-0.63; p<0.001; n=56,770 patients), patients with limited stage disease (HR 0.60; 95% CI, 0.55-0.65; p<0.001; n=78 studies; n=27,137 patients), and patients with extensive stage disease (HR 0.59; 95% CI, 0.51-0.70; p<0.001; n=28 studies; n=26,467 patients). Between-study heterogeneity was significant when pooled amongst all studies (I2=73.6%; 95% CI 68.4%-77.9%). Subgroup analysis did not reveal sources of heterogeneity. In a subgroup analysis on studies that used magnetic resonance imaging to exclude presence of brain metastases at restaging among all patients, overall survival did not differ significantly between patients who did or did not receive PCI (HR 0.74; 95% CI, 0.52-1.05; p=0.08; n=9 studies; n=1384 patients). Our findings suggested that administration of PCI is associated with a survival benefit, but not when considering studies that radiographically confirmed absence of brain metastases, suggesting that the survival benefit conferred by PCI might be therapeutic rather than prophylactic. No funding.