bluuebunny/crossref_metadata_2025 huggingface dataset:
Studying the usability of recycled aggregate to produce new concrete
Authors: Qasim Ola Adel , Hilal Nahla , Al Biajawi Mohammad I. , Sor Nadhim Hamah , Tawfik Taher A.
Published: June 2024

One of the most significant environmental issues worldwide is garbage, particularly waste from construction materials, which is generated in substantial numbers. However, in the building industry, the significant extraction of natural resources such as cement, natural sand, and natural gravel poses a critical environmental challenge, depleting these resources at an alarming rate. There are some solutions that developed countries are resorting to, namely the division of construction waste into groups, where it is reused under the name of recycling construction waste to produce new, environmentally friendly building materials. The aim of this research includes a laboratory process study as it includes the use of the following ratios: 0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100%, under the process of replacing coarse plain aggregates including coarse recycled aggregates and studying the most important mechanical properties of concrete. This research was carried out using fresh concrete properties such as workability tests and hardened concrete properties such as compressive strength, splitting, and flexural tensile strength examined at the durations of 7, 14, and 28 days. The research includes the investigation of the three main properties of concrete. After conducting the tests, the results have shown that the main property of recycled concrete is lower strength than that of conventional concrete, but it can be said that it is within the limits that can be used for construction. The results also showed that compared to normal aggregates, development in the recycled aggregate percentage rates reduces the operational workability of concrete. The research proved that the maximum decrease in compressive, flexural, and tensile strength, density and the slump were 19.4, 18.3, 19.6, 19.5, and 25.0% respectively compared to the control concrete samples.
A retrospective comparison of abbreviated course “7+7” vs standard hypomethylating agent plus venetoclax doublets in older/unfit patients with newly diagnosed acute myeloid leukemia.
Authors: Bazinet Alexandre , Dinardo Courtney Denton , Arani Naszrin , Bataller Alex , Rausch Caitlin R , Maiti Abhishek , Swaminathan Mahesh , Daver Naval Guastad , Kadia Tapan M. , Ravandi-Kashani Farhad , Kantarjian Hagop M. , Chraibi Samy , Decroocq Justine , Pascal Laurent , Lebon Delphine , Bonnet Sarah , Gauthier Nicolas , Pages Arnaud , De Botton Stéphane , Willekens Christophe
Published: June 2024

6507

Background: Hypomethylating agent (HMA) plus venetoclax (VEN) regimens are standard of care in older/chemotherapy ineligible patients with acute myeloid leukemia (AML). While the VEN label recommends continuous 28-day cycles, shortened VEN durations may mitigate cytopenias and improve tolerability. It is unknown how shorter VEN cycles compare to standard HMA+VEN in terms of efficacy/safety. Methods: We performed a retrospective comparison of patients with newly diagnosed (ND) AML treated with azacitidine (AZA) x 7 days plus VEN x 7 days (“7+7” regimen) at 7 French centers (n=82, Willekens, ASH 2022) vs patients treated with standard dose HMA+VEN (s-HMA/VEN) at a US center (n=173), generally consisting of 21-28 days of VEN. We compared composite complete remission rate (CRc, consisting of CR + CRi), overall survival (OS), event-free survival (EFS), and myelosuppression between regimens. Results: Baseline characteristics are shown in the table. The s-HMA-VEN group consisted of 10-day decitabine (DAC) in 59% with the remaining patients receiving 5-day DAC or 7-day AZA. The CRc rate was similar; 72% with “7+7” vs 71% with s-HMA/VEN (p=0.89). The CR rate was 57% with “7+7” vs 55% with s-HMA/VEN (p=0.72). Median cycles to first response was 1 in both groups, however 42% of responders on “7+7” required more than 1 cycle for first response whereas almost all responders on s-HMA-VEN (99%) had a first response after cycle 1. Median cycles to best response was 2 with “7+7” vs 1 with s-HMA-VEN (p=0.02). 4-week mortality was similar (2% with “7+7”, 6% with s-HMA-VEN; p=0.24). 8-week mortality was higher with s-HMA-VEN (17%) compared to “7+7” (6%) (p=0.02). The median OS was 11.2 months (2-year 28%) with “7+7” vs 10.1 months (2-year 33%) with s-HMA/VEN (p=0.93). Outcomes stratified by molecular groups will be updated at the meeting. Fewer patients required platelet transfusions during cycle 1 with “7+7” compared to s-HMA/VEN (62% vs 77%, p=0.01). The cycle 1 rates of neutropenic fever and red cell transfusion requirements were similar. Conclusions: Acknowledging the limitations of a retrospective comparison across multiple centers, we did not observe a signal for a difference in efficacy between "7+7" vs standard VEN-based HMA doublets in ND-AML. The “7+7” regimen was associated with lower platelet transfusion requirements and lower 8-week mortality. [Table: see text]
Safety outcomes in patients with acute myeloid leukemia receiving gemtuzumab ozogamicin and proceeding to allogeneic hematopoietic stem cell transplantation.
Authors: Kebriaei Partow , Ho Vincent , Perales Miguel-Angel , Bejanyan Nelli , Kaur Manmeet , Zhang Mei-Jie , D'Amico Paul G. , Purcell Simon , Dorman Stephanie , Vandendries Erik , Asomaning Kofi , Saber Wael
Published: June 2024

6516

Background: Gemtuzumab ozogamicin (GO) is a CD33-directed antibody-drug conjugate approved by the FDA in 2017 for the treatment of newly diagnosed and relapsed/refractory (R/R) CD33-positive acute myeloid leukemia (AML) in adults and pediatric patients of 1 month and older and 2 years and older, respectively. Previous data have associated GO with adverse events (AEs) including hepatotoxicity and hepatic veno-occlusive disease (VOD). Patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) may be at greater risk of VOD with GO. This study aimed to characterize AEs after HSCT in adult patients with AML who were treated with GO. Methods: This non-interventional post-authorization safety study used de-identified healthcare data from the Center for International Blood and Marrow Transplant Research (CIBMTR) database. Data were collected from 01 September 2017. Safety outcomes post-HSCT were evaluated in adult patients with newly diagnosed or R/R AML who received GO prior to first HSCT. Data cutoff was 04 July 2023. Results: We present the interim data of 157 patients from 24 centers with a median follow-up of 12.9 months (range, 3.0-49.7). At the time of HSCT, 84 patients were in first complete remission (CR1), 48 patients were in second CR (CR2) and 25 patients were in third or greater CR, relapse or primary induction failure (CR3, n=5; Rel, n=12; PIF, n=8). Most patients (n=105; 67%) received GO as first line therapy. Median lines of therapy prior to HSCT were 2, 3.5 and 5 in CR1, CR2 and CR3/Rel/PIF groups, respectively. Median age was 52.5 y (range, 18.7-74.9); 53% male. Time from diagnosis to first GO dose was <3 months for most patients (n=120; 76%). Total cumulative GO dose was 1-3 mg/m2 in 25 (16%), 4-6 mg/m2 in 28 (18%), 7-9 mg/m2 in 45 (29%) and ≥10 mg/m2 in 14 (9%) patients. The most common HSCT donor type was unrelated (n=93; 59%), and 55% of patients received myeloablative conditioning regimens. Non-fatal VOD was reported in 7 (4%) patients. Median time from HSCT to VOD was 0.9 months (range, 0.4-2.2). No VOD-related deaths occurred. Outcome probabilities for 6-month transplant-related mortality (TRM) were 8% (95% CI, 4-13) and 5% (95% CI, 2-8) for 100-day VOD. Conclusions: The use of GO appears to be safe prior to HSCT in adults with AML. Rates for 100-day VOD and TRM were comparable to those previously reported for patients with AML who received HSCT with or without prior GO. Clinical trial information: B1767034.
A real-world picture of patients with a new diagnosis of acute myeloid leukemia in Italy.
Authors: Esposito Immacolata , Ronconi Giulia , Dondi Letizia , Calabria Silvia , Piccinni Carlo , Dondi Leonardo , Dell'anno Irene , Addesi Alice , Martini Nello
Published: June 2024

6520

Background: Acute myeloid leukemia (AML) is a blood malignancy with poor prognosis. Antineoplastic strategies are still mostly restricted to fit patients. This analysis of administrative healthcare data identified and described newly AML diagnosed patients, their antineoplastic treatment and survival from the perspective of the Italian National Health Service (SSN). Methods: From the Fondazione ReS (Ricerca e Salute) database (~5 million inhabitants/year), among adults with primary/secondary in-hospital diagnosis of AML in 2018 (index date) and analysable look-back period until 2013, patients newly AML diagnosed were selected. They were characterized by age, sex and comorbidities (cardiometabolic, thyroid and cerebrovascular disorders, chronic kidney and liver disease, and inflammatory bowel diseases). During 1 year following index date, antineoplastic treatment and allogeneic stem cell transplantation (alloSCT) were assessed. Among patients undergoing antineoplastic therapy, those fit and unfit for intensive chemotherapy (ICHT) were categorized according to proxies based on the setting of chemotherapy administration (i.e., overnight hospitalization=fit, while daily hospitalization or local outpatient ambulatory=unfit). The 2-year overall survival (OS) of treated patients was assessed through a Kaplan Meyer analysis. Results: In 2018, 228 newly AML diagnosed patients (incidence: 5.7x100,000 adult inhabitants) were identified. Males were 56.6%. Mean age was 69±16 years, and 61% patients had ≥2 comorbidities. During 1 year following index date, 75% of newly AML diagnosed patients received antineoplastic treatment (males were 57%, mean age was 66±15 years, and 49% had ≥2 comorbidities). Of them, 19% underwent alloSCT (mean age was 50±14 years). On average, remaining untreated patients (57/228; 25%) were older (77±14 years) and affected by more comorbidities (79% with ≥2 comorbidities) than treated patients. At 2 years following index date, 97% of treated patients survived (vs 65% of untreated patients; p<0.01). Among treated patients, 51% (mean age was 64±15 years) were considered fit for ICHT, and 24% were considered unfit for ICHT (mean age was 71±15 years). At 2 years following index date, 38% of patients fit for ICHT survived (vs 29% of patients unfit for ICHT; p<0.01). Conclusions: This real-word analysis suggests that patients receiving antineoplastic treatments, regardless of a following alloSCT, were younger and affected by less comorbidities than untreated patients. Also, older patients are likely to be excluded from the ICHT option, as recommended by most of guidelines. However, these findings suggest that being treated with chemotherapy and/or alloSCT can increase survival probabilities.
CASTOR1 phosphorylation as a predictor of survival in male patients with KRAS-mutated lung adenocarcinoma.
Authors: Loo Suet Kee , Sica Gabriel , Wang Xian , Li Tingting , Chen Luping , Gaither-Davis Autumn , Huang Yufei , Burns Timothy F. , Stabile Laura P. , Gao Shou-Jiang
Published: June 2024

e20015

Background: Lung cancer, a leading global cause of cancer-related mortality, necessitates enhanced prognostic markers for improved treatment outcomes. This study focuses on the predictive value of phosphorylated cytosolic arginine sensor for mTORC1 subunit 1 at S14 (pCASTOR1) in lung adenocarcinoma (LUAD) patients, specifically in males with KRAS mutations. Methods: This retrospective study, approved by University of Pittsburgh IRB, utilized formaline-fixed paraffin embedded primary tissues from two independent cohorts of patients who underwent thoracic surgical procedures at the University of Pittsburgh Medical Center (UPMC) from 2002 to 2011. Comprehensive clinical, demographical and pathological information was obtained from UPMC Cancer Registry, with cases lacking incomplete information excluded from analysis. Study endpoints included overall survival (OS) and relapse-free survival (RFS). An antibody targeting pCASTOR1 was employed to analyze LUAD tumor and adjacent non-tumor lung tissues from both cohorts. A pathologist, blinded to patient information and survival outcomes, conducted scoring in 5% increments. Scores were categorized as low or high pCASTOR1 based on second or third quartile. Correlations between pCASTOR1 scores and OS/RFS were examined, stratifying by clinical, pathological, demographic, or genotype data. Univariate OS and RFS analyses were conducted using the Kaplan-Meier method and log-rank test, while multivariate survival significance was assessed via Cox regression analysis. Additionally, unpaired T-tests were utilized to compare pCASTOR1 levels between non-tumor and tumor cells. A significance threshold of p < 0.05 was applied for all analyses. Results: Tumor cells exhibited significantly elevated pCASTOR1 scores compared to non-tumor cells in both cohorts (P < 0.05). High pCASTOR1 scores predicted poor OS (HR = 3.3, P = 0.0008) and RFS (HR = 3.0, P = 0.0035) in male patients with KRAS mutations in Cohort 1. pCASTOR1 remained an independent predictor for OS (HR = 4.1, P = 0.0047) and RFS (HR = 3.5, P = 0.0342) after controlling for other factors. Cohort 2, comprised solely of smokers with incomplete genotype information, validated these findings, with high pCASTOR1 scores correlating with worse OS (HR = 4.8, P = 0.0363). Notably, in early-stage LUAD, elevated pCASTOR1 scores were associated with significantly worse OS (HR = 3.3, P = 0.0176) and RFS (HR = 3.1, P = 0.0277) in male patients with KRAS mutations in Cohort 1, and worse OS (HR = 5.0, P = 0.0069) and RFS (HR = 5.0, P = 0.0069) in Cohort 2, akin to late-stage patients. Conclusions: Elevated pCASTOR1 score serves as a robust biomarker predicting poor OS and RFS in male LUAD patients with KRAS mutations, offering potential clinical utility in optimizing treatment strategies for this subgroup.
Comprehensive germline and somatic DDR genomic profiles of Chinese patients with multiple primary lung cancer.
Authors: Yang Yingshun , Li Mingwei , Wang Shuai , Pei Guotian , Qin Jiayue , Cao Shanbo , Huang Yuqing
Published: June 2024

e20019

Background: The number of multiple primary lung cancer (MPLC) patients has rapidly increased in recent years. Disruption of the DNA damage repair (DDR) gene is related to cancer risk, progression, and treatment selection. However, the characteristics and significance of DDR alterations remain undefined in MPLC. Methods: A total of 133 Chinese MPLC patients with 308 lesions were enrolled and 784 single-focus lung cancer (SFLC) patients were analyzed as a control in the present study. Genetic testing was performed by utilizing the next-generation sequencing (NGS) of 808 cancer-related genes including 276 DDR genes. The patients were divided into 3 groups: DDR-germline (germline variants, N = 11), DDR-somatic group (somatic variants, N = 98), and the non-DDR group (no DDR variants, N = 24). Results: The overall DDR variants were identified in 82.0% (109/133) of the patients, and a total of 283 variants were found, with almost all being somatic (254/283). The most commonly germline alterations were found in RAD50 (1.5%), WRN (1.5%) and BRCA2 (0.8%), while in the somatic mutations, TP53 (26.3%) showed the highest frequency. DDR-somatic group was more likely to have alterations in TP53, LRP1B, ERBB2 and MYC compared with DDR-germline group. Taken non-DDR group as reference, mutations in TP53 (P<0.05), ALK and PIK3CA were more common in DDR-germline group, but EGFR, RBM10, TP53, LRP1B, TERT and MYC (all P<0.05) in DDR-somatic group. Furthermore, the DDR-somatic group exhibits the highest median tumor mutational burden (6.56) compared with 3.55 (P<0.01) in DDR-germline and 3.69 (P<0.01) in non-DDR group. In addition, the copy number variation (CNV) was statistically different among the three groups (P<0.001). The proportion of copy number gain patients in DDR-somatic group is the highest (28.3%) compared with 12.0% in DDR-germline group and 10.9% in non-DDR group (P<0.01). DDR-somatic MPLC and SFLC patients possessed distinct somatic genomic characteristics, especially with significantly different prevalence in TP53, RBM10, KRAS, BRAF, and ALK (all P<0.05). Moreover, we also found notable differences in the prevalence of TP53 and CNV (both P<0.05) between DDR-germline MPLC and SFLC patients. Conclusions: MPLC patients exhibit a distinctive DDR mutations landscape. The differences in the mutation profile between the DDR-germline and DDR-somatic groups and the distinct actionable genes may indicate the different target-therapy choices for MPLC patients.
Induction immune checkpoint inhibitors and chemotherapy for patients with stage III non-small cell lung cancer: A real-world experience.
Authors: Zheng Shuohan , Sun Ciming , Zhang Hao , Xu Huimin , Dong Baiqiang , Hou Zan , Chen Ming , Li QiWen
Published: June 2024

e20057

Background: Immune checkpoint inhibitors (ICIs) have become the standard consolidation therapy for stage III unresectable non-small cell lung cancer (NSCLC). Whether induction ICIs combined with chemotherapy can further improve efficacy is controversial. In this study, we used real-world data to explore the possibility of ICIs plus chemotherapy before definitive chemoradiation therapy (CRT). Methods: Patients with stage III NSCLC (including postoperative recurrence), who received definitive CRT from 2016 to 2022, was retrospective reviewed. Survival outcomes and the incidence of pneumonia were calculated and compared between patients with induction ICIs plus chemotherapy or not. Results: A total of 156 patients undergoing definitive RCT were analyzed. Among them, 103 patients received induction ICIs plus chemotherapy, and 53 patients received induction chemotherapy before RCT or concurrent chemoradiotherapy. The 5-year overall survival (OS) rates were 75.0% and 44.4%, respectively. The median OS was not reached (NR) and 36.5 months, indicating a significant improvement of survival with the addition of induction ICIs (P = 0.03). However, there were no significant differences between the two groups in median progression-free survival (PFS) (22.4 vs. 13.6 months; P = 0.09), locoregional recurrence-free survival (LRFS) (38.0 vs. 36.9 months; P = 0.73), and distant metastasis-free survival (DMFS) (37.8 vs. 25.5 months; P = 0.14). Multivariate analysis showed that induction ICIs plus chemotherapy was an independent favorable prognostic factor for OS (HR 2.89; 95% CI, 1.24-6.75; P = 0.01). The incidence of grade 2 or higher pneumonia in the two groups was 37.2% and 29.2%, respectively (P = 0.35). Additionally, we found that patients with consolidation ICIs after induction ICIs had a better OS, with a 4-year OS rate of 90.7% and 65.5% (P = 0.03). Patients undergoing 5-6 cycles of induction ICIs seemed to have a better outcome compared to those with 3-4 cycles or 1-2 cycles (93.8% vs. 77.4% vs. 60.5%). Conclusions: For patients with stage III NSCLC receiving definitive CRT, the combination of induction ICIs and chemotherapy improves OS without a significant increase of pneumonia in real-world practice. This treatment strategy warrants further research.
Effect of intrinsic STING of CD8+T cells on self-metabolic reprogramming and anti-tumor effects.
Authors: Xu Qiuli , Hua Xin , Li Bingbing , Jiang Bei , Xu Ruiqing , Lv Tangfeng , Song Yong
Published: June 2024

e20062

Background: Many preclinical studies have demonstrated that STING agonists have effective anti-tumor effects, but their adverse effects prevent practical use. Previous research by our team has demonstrated that STING has a more significant anti-tumor role in host immune cells than tumor cells, and the level of STING mRNA is associated with the outcome of immunotherapy in non-small cell lung cancer. Although STING is necessary for CD8+T cells to exert immunological activity, its effect on CD8+T cells is debatable. Therefore, we will concentrate on the particular roles of STING in CD8+T cells. Methods: We used in vitro and in vivo models to confirm the influence of STING on CD8+T cell function. We examined the impact of STING on CD8+T cell metabolic function using RNA-seq, Seahorse, flow, electron microscopy, and other techniques. STING knockout mice were used to study the effect of competitive inhibition of glycolytic products during immunotherapy. In addition, we collected peripheral blood immune cells from 30 immunotherapy patients to examine the correlation between immune cell glycolysis levels and immunotherapy efficacy. Results: RNA-seq showed significant changes in signaling pathways such as glycolysis/glycogen synthesis, oxidative phosphorylation, tricarboxylic acid cycle, and one carbon unit in STING-/- CD8+T cells. In vitro experiments revealed that the inactivation of the STING gene reduced the number of mitochondria, altered the choice of metabolic pathways, and impaired the anti-tumor ability. Flow results showed that the mean fluorescence intensity of mitochondria in STING-/- CD8+T decreased. Seahorse experiment showed that STING-/- CD8+T glycolysis was enhanced, and oxidative phosphorylation was decreased. Meanwhile, the content of lactic acid in the culture supernatant of STING-/- CD8+ T increased dramatically, the high level of lactic acid further inhibited the proliferation of CD8+ T and the secretion of IFN-γ. Competitive inhibition of the glycolysis process or lactic acid formation can save the function of STING-/- CD8+ T cells and the secretion of IFN-γ, save the immunotherapy effect of STING-/- mice. This provides a new therapeutic idea for patients with low STING expression and poor immunotherapy response. In the peripheral blood immune cells of immunotherapy patients, we observed a negative correlation between the mRNA levels of glycolysis-associated molecules and STING. Additionally, we found a correlation between the levels of glycolysis-associated molecules in immune cells and immunotherapy efficacy outcomes. Conclusions: Our study is the first to explore the effect of STING on the metabolic process in CD8+ T cells. Intervening in the metabolic process of STING-deficient CD8+ T can save the efficacy of immunotherapy.
Pulmonary blastoma: An NCDB analysis of demographic and socioeconomic factors.
Authors: Ramos Brianna Eillen , Tade Yanick , Khatib Rawaan , Sadighian Assal , Silberstein Peter T. , Heise Craig , Hsia Beau
Published: June 2024

e20069

Background: Pulmonary blastoma (PB) is a rare sarcomatoid carcinoma classified as a non-small cell lung cancer with a poor prognosis and no standard treatment. This malignancy exhibits glandular proliferation with a morular component resembling embryonic development. Leading PB treatment favors surgical resection with concurrent chemotherapy. However, radiation is recommended for inoperable tumors. Further analysis of diagnostic trends may provide information about the epidemiology of PB. The National Cancer Database (NCDB) was analyzed to establish the demographic factors in diagnosed patients. Methods: A retrospective cohort study from 2004 to 2020 was conducted using the NCDB. 146 patients were identified with a histologically confirmed diagnosis of PB (ICD-O-3 code 8972). Race, gender, Hispanic origin, urban/rural residence, insurance coverage, treatment approaches, and mean survival rates were analyzed via descriptive statistics. Regression analysis was performed to examine incidence trends. Results: 146 patients diagnosed with PB were identified in the NCDB, where the incidence rate of diagnoses strongly declined annually (R² = 0.079). The average age of diagnosis was 50 years (SD = 26, range = 1-90 years), with women (56%) more likely to be affected than men (44%). The majority of patients identified as White (80%) and non-Hispanic (88%), lived in metropolitan counties with a population greater than 1 million (58%), and were privately insured (45%). The top primary sites of diagnoses were the upper (38%) and lower (28%) lobe of the bronchus or lung. For patients who did not receive palliative care (93%), many received surgery (75%) as their primary treatment. Within this group, chemotherapy and radiation therapy were also chosen as treatment options (48% and 27%, respectively). The majority of individuals (66%) had a Charlson-Deyo comorbidity score of 0. The survival rates were 58% at two years, 49% at five years, and 34% at ten years. The mean survival was also found to be 86 months. Conclusions: To the best of our knowledge, this is the first NCDB analysis on pulmonary blastoma and helps provide insight on a previously understudied topic. Results demonstrated that the majority of PB patients are non-Hispanic White females, who were primarily diagnosed at the upper lobe of the bronchus or lung. These findings confirmed similar descriptions from other databases and earlier case reports. This is the first time the socioeconomic factors of PB patients have been described in the literature: PB patients typically do not receive palliative care and choose to undergo surgery as their primary treatment. Further research is indicated to provide a greater insight on the effects of demographic/socioeconomic factors on diagnostic criteria, chosen treatments, and overall survival rates of patients with PB.
The treatment modalities and radiotherapy pattern in patients with primary lung cancer in Japan.
Authors: Hu Qingqing , Huang Titan , Nakajo Ko , Zhang Yongjing , Qiu Hong
Published: June 2024

e20070

Background: In Japan, lung cancer has high incidence and mortality among all cancers. The study is to understand the existing status of the treatment modalities in Japan, especially for radiotherapy (RT). Methods: This was a retrospective cohort study using the Japan Medical Data Center (JMDC) database. A cohort of adult patients with at least two diagnosis codes of primary lung cancer (ICD-10-CM: C34) during January 1st, 2015-March 31st, 2023, and initiated lung cancer treatment was included in the study. The initial treatment episode was defined as a period with the first single or multiple treatments before a 90-day gap. Patients were followed up until a record of death, or the last enrollment in JMDC. The cohort was stratified into four exclusive groups: Group A: ≥1 record of distant metastasis; Group B-1: ≥1 record of regional metastasis; Group B-2: no record of surgery and no metastasis; Group C: ≥1 record of surgery and no metastasis. The characteristics, initial treatment episode and RT patterns were described across the four groups. Results: A total of 9,373 patients were included, with Group A 1,625 (17.3%), Group B-1 527 (5.6%), Group B-2 2084 (22.2%), and Group C 5137 (54.8%). The median follow-up was 21.2 months of the cohort. The median (IQR) time to initial treatment episode from the initial diagnosis was 27 (27), 35 (40), 34 (47) and 38 (36) days for the four groups, respectively. Most of patients in group A (74.1%), B-1 (70.8%), and B-2 (67.6%) had a >3 months duration of initial treatment, and only 32.7% in group C. For treatment involved in the initial treatment episode, RT was accounted for 59.2%, 29.8%, 43.4%, and 4.7% in four groups respectively. For treatment categories in Groups A, B-1, and B-2, RT only was performed in 15.5%, 2.2% and 6.9% of patients with single treatment; and RT was commonly performed with chemotherapy in multiple treatments, with proportions of 83.6%, 95.3% and 95.6% among no surgery. For RT with chemotherapy group, the median RT fractions are 22, 36 and 42, covering a median duration of 35, 43 and 43 days of RT. Conclusions: In Japan, the initial treatment episode usually starts in 30 days and lasts more than 3 months for metastasis and unresectable primary lung cancer. RT only is not commonly performed, and RT with chemotherapy is commonly performed in initial treatment episode. [Table: see text]
Fetal adenocarcinoma: An NCDB analysis of socioeconomic and demographic factors.
Authors: Han Emily , Moroz Mark , Puvvadi Suraj , Joseph Angel , Silberstein Peter T. , Heise Craig , Hsia Beau
Published: June 2024

e20076

Background: Fetal adenocarcinoma (FA) is a rare subtype of lung neoplasia whose structure is similar to a developing fetal lung. Chest x-ray is valuable for diagnosis as 25 - 40% of patients with FA are asymptomatic. FA is classified into low-grade and high-grade, predominantly occurring in children and older males with a smoking history. The rarity of FA suggests that evaluating its diagnostic patterns could expand awareness of its epidemiology. Impactful demographic factors of FA were established through analysis of the National Cancer Database (NCDB). Methods: The 2004 - 2020 National Cancer Database (NCDB) was utilized to perform a retrospective analysis of all 120 patients with a histologically confirmed diagnosis of FA (ICD-O-3 Code 8333). Descriptive statistics were employed to examine demographic factors, including sex, age, race, Hispanic ethnicity, urban/rural residence, Charlson-Deyo comorbidity score (CDCS), and treatment facility type. Additionally, regression analysis was utilized to demonstrate incidence trends. Exclusion criteria included missing values. Results: The NCDB identified 120 patients from 2004 - 2020. Over this time period, there was a slightly increasing incidence of patients diagnosed per year (R2 = 0.4461). Represented age at diagnosis featured negative skewness (-0.8), and the mean age was 54.4 years (95% CI = 51.2 - 57.6, SD = 17.6). Most patients were female (57%), White (76%), and non-Hispanic (95%). The vast majority of patients (85%) resided in metropolitan areas, with a slight majority of patients (53%) hailing from areas of 1 million population or more. Regions of the United States were well-represented, with a plurality of patients from the South Atlantic (21%). Most patients were diagnosed at Stage I (56%) and had a CDCS of 0 (61%). The primary tumor site was the upper lung lobes, and most (83%) patients underwent surgery as primary treatment. Multiple facility types were utilized in the care of patients, including research programs (42%), comprehensive community cancer center programs (30%), and integrated network cancer programs (25%). The 30-day mortality rate was 1%, comparable to the 90-day mortality rate of 3%. Five years after diagnosis, 60% of patients were alive. Conclusions: To the best of our knowledge, this is the first NCDB analysis to examine the sociodemographic factors concerning prognosis in patients with FA. Our results are consistent with previous studies finding that patients with low-stage FA tend to have favorable outcomes. Our study is the first documentation of location demographics of patients with FA: Most patients live in metropolitan counties along the Atlantic Coast. Future investigations on the prognostic significance of demographic and socioeconomic factors should be performed to optimize treatment approaches for improved mortality rates of diverse patients with FA.
Long-term survival of single and multifocal stage 1 lung carcinoma using image-guided thermal ablation.
Authors: Jahanshahi Noor J. , Kooraki Soheil , Villegas Bianca , Kim Grace Hyun J. , Goldman Jonathan W. , Genshaft Scott J. , Suh Robert D. , Abtin Fereidoun
Published: June 2024

e20087

Background: Image-guided thermal ablation (IGTA) is an effective treatment option for patients with non-small cell lung cancers (NSCLC), offering an excellent alternative to invasive surgery. We seek to compare long-term survival metrics between single and multifocal stage IA NSCLC patients who underwent IGTA. Methods: IRB-approved, HIPAA-compliant, retrospective study of patients who underwent IGTA for NSCLC during 2015 and 2016. Patient demographics, clinical and imaging follow-ups, tumor characteristics, and procedural technical outcomes were reviewed. We analyzed technical success, 5-year overall survival (OS), progression-free survival (PFS), cancer-specific survival (CSS), and Kaplan-Meier survival analysis between single and multifocal NSCLC cohorts, as well as different tumor stages. Results: 37 patients (mean ± SD age=71.6±8.8) ablated for single (n=15 (40.5%)) or multifocal (n=22 (59.5%)) NSCLC were identified. Multifocal NSCLC were sub-classified into 2-3 (n=12 (32.4%)) and ≥4 tumors (n=10 (27%)). All ablations were completed successfully. Across 119 IGTA encounters, patients were treated using cryoablation (n=66), microwave ablation (MWA) (n=49), and radiofrequency ablation (RFA) (n=4). At the time of ablation, individual nodules were staged at T1A=46 (38.7%), T1B=54 (45.4%), T1C=16 (13.5%) and T2A=3 (2.5%). Local recurrence was observed in 4/119 (3.3%) tumors; two were reablated once with MWA and cryoablation with no further recurrence, the third was reablated twice with MWA and had no recurrence, and the fourth was reablated once with MWA and subsequently treated with radiotherapy. Multifocal NSCLC patients exhibited significantly better 5-year OS of 85.6% compared to single NSCLC patients at 35.7% (HR=0.14, p=0.003, 95% CI: 0.037, 0.51). PFS and CSS at 5 years were higher for multifocal NSCLC compared to single NSCLC, but only significant for PFS (HR=0.25, p=0.014, 95% CI: 0.084, 0.76). PFS and CSS of subjects with ≥4 tumors were both 100%, 2-3 tumors at 58.7% and 90.9%, and single tumors at 35.7% and 83.1%, respectively. There was no significant difference between tumor T stages for OS and PFS (p=0.48 and p=0.56, respectively; see Table). No patient staged at T1A at the initial IGTA encounter died as a result of cancer, meaning cancer-specific survival was greatest in T1A tumors (see Table). Conclusions: IGTA is an effective treatment for multifocal and early-stage NSCLC. Our results demonstrated consistent trends in improved survival for multifocal NSCLC. The size of tumor up to 3 cm did not have significant impact on overall survival or progression-free survival. [Table: see text]
Brain metastases in patients with pleural mesothelioma receiving dual checkpoint blockade compared to single-agent checkpoint blockade or chemotherapy.
Authors: Stalker Margaret , Walker Suzanne , Lebow Emily S. , Anderson Evan P. , Roshkovan Leonid , Katz Sharyn I. , Litzky Leslie , Haas Andrew R. , Singhal Sunil , Langer Corey J. , Cengel Keith A. , Marmarelis Melina Elpi
Published: June 2024

e20093

Background: Immunotherapy (IO) has emerged as a treatment option in pleural mesothelioma (PM). Historically, brain metastases (BM) in PM were rare, thus brain imaging is not routine practice or included in guidelines. We characterize the incidence of BMs by type of treatment received. Methods: In this retrospective analysis,adult patients with PM treated at the Hospital of the University of Pennsylvania between 1/1/2015- 8/31/2023 were included. Patient demographic data, treatment, brain imaging and clinical history were extracted from the electronic medical record.A two-tailed Z score with alpha 0.05 was used to determine a difference in proportion of patients with BM by treatment group. Results: 290 patients were included in the study. 154 (53.1%) were treated with chemotherapy (CT), 94 (32.4%) were treated with pembrolizumab (pembro), 39 (13.4%) were treated with ipilimumab + nivolumab (ipi/nivo), and 3 (1.0%) were treated with another IO. A higher proportion of patients treated with ipi/nivo developed BM compared to those treated with pembro alone (4/39, 10.3% vs 2/94, 2.1%; Z score p= 0.038). None of the 154 patients treated with CT developed BM. All BMs were detected due to symptoms. Of the six patients that developed BM, the median age was 72.5 (range 47-80), 83% were male, 67% identified as Caucasian, and there was an even distribution of histology with 33% each of epithelioid, biphasic, and sarcomatoid. All patients received IO most recently or were currently on it when BM developed. Median time to BM from start of immunotherapy was 144.5 days (range 2-913 days). On imaging, all 6 patients had edema surrounding the brain metastases and 4 also showed hemorrhage. Survival after development of BM was poor (Table1). Four patients (67%) underwent surgery for the BM, while all patients received brain radiation. Two patients received whole brain radiation therapy (WBRT), while four patients received stereotactic radiosurgery (SRS) to a median of four brain metastases (range 1-7). Three patients developed subsequent intracranial progression (out-of-field) including one with rapid intracranial progression 20 days post-radiation. Conclusions: In this large retrospective study of patients with PM treated with systemic therapy, BM was most prevalent in those patients receiving ipi/nivo compared to pembro alone and not seen in those receiving chemotherapy. The presence of edema suggests a possible immune infiltrate while on IO (correlative studies in progress). Brain imaging should be considered prior to starting IO in patients with PM. [Table: see text]
Helical tomotherapy was superior to intensity-modulated radiation therapy in hippocampal avoidance prophylactic cranial irradiation in patients with limited-stage small-cell lung cancer.
Authors: Lu Shuangqing , Gong Guanzhong , Liu Haoyu , Tian Yaru , Li Wanhu , Zhou Jingrun , Niu Jiling , Zhu Hui
Published: June 2024

e20099

Background: Hippocampal avoidance (HA) techniques have been developed to reduce the risk of neurocognitive dysfunction associated with prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer (LS-SCLC). However, applying different radiotherapy techniques to HA has not yet been further analyzed. This study discussed the dosimetric differences between intensity-modulated radiation therapy (IMRT) and helical tomotherapy (TOMO) in HA-PCI and analyzed the benefit of the dosimetric advantage in the risk of brain metastasis (BM) from a clinical perspective. Methods: We retrospectively evaluated patients who underwent PCI from June 2020 to December 2021 at Shandong Cancer Hospital. They were divided according to hippocampal avoidance and radiotherapy techniques: IMRT without HA (non-HA-IMRT), HA-IMRT, and HA-TOMO. The cumulative incidence of BM, target coverage (TC), homogeneity index (HI), conformity index (CI), and hippocampal doses of these radiotherapy programs were evaluated. Results: One hundred seventy-two patients were included in the analysis: 56, 78, and 38 patients in the non-HA-IMRT, HA-TOMO, and HA-IMRT groups, respectively. The 2-year cumulative incidence of BM was 31.4% in patients with HA (78 patients in the HA-TOMO group and 38 patients in the HA-IMRT group) and 23.2% in patients without HA (hazard ratio [HR]: 0.75, 95% confidence interval [95% CI]: 0.43-1.31; P= 0.340). However, the 2-year cumulative incidence of BM was lower in the HA-TOMO group than in the HA-IMRT group (25.0% vs. 44.7%, HR: 0.51, 95% CI: 0.26-0.99; P= 0.029). Both techniques achieved hippocampal protection, but HA-TOMO accomplished significantly better TC (96.24%±0.65% vs. 93.75%±2.45%, P< 0.001), HI (0.09±0.02 vs. 0.27±0.12, P< 0.001), and CI (0.88±0.02 vs. 0.85±0.04, P< 0.001). Conclusions: HA-PCI did not increase BM risk. Additionally, HA-TOMO could achieve better TC, HI, and CI with respect to the planned tumor in the brain while achieving more rapid dosing in the hippocampal region. The cumulative incidence of BM was lower with HA-TOMO than with HA-IMRT.
Olaparib, AZD1390, ceralasertib, saruparib and consolidation durvalumab (CONCORDE) phase Ib platform study of novel DNA damage response inhibitor (DDRi) agents in combination with radiotherapy in non-small cell lung cancer (NSCLC).
Authors: Greystoke Alastair , Oughton Jamie B. , Brown Sarah R , Butterworth Karl , Coyle Victoria , Franks Kevin , Hassani Adam , Harrow Stephen , Hatton Matthew , Hiley Crispin T. , Kendall Jessica , Phillip Rachel , Norris Matthew , Ojo Oluwaseun , Shaw Paul , Walker Fiona , Yang Huiqi , Chalmers Anthony J. , Faivre-Finn Corinne
Published: June 2024

TPS8119

Background: Lung cancer is the leading cause of cancer mortality globally, with cases projected to exceed 62,000 by 2035. Outcomes remain poor despite advances in radiotherapy (RT) technologies. Combining novel mechanism-based agents with RT could improve the therapeutic index. DNA inhibition of cellular response to radiation-induced DNA damage can overcome intrinsic radio resistance and poses a promising strategy. Methods: CONCORDE is an open label, randomised, multi-arm, phase Ib, clinical trial opened to accrual in 11 UK hospitals designed to assess multiple DDRi in combination with radical thoracic RT (60Gy in 30 fractions over 6 weeks). Patients are randomised 3:1 to RT+/-DDRi. The study utilises an adaptive Bayesian model-based approach to dose escalation aiming to identify the recommended phase II dose for each treatment combination. Two arms will deliver up to 12 months consolidation durvalumab+/-DDRi following RT. Patients are eligible based on key criteria: not suitable for concurrent chemotherapy RT, inoperable, stage IIB/III NSCLC, performance status (KPS≥70). The dose limiting toxicity (DLT) period for treatment-related toxicities is 13.5 months post start of RT treatment, with most toxicities expected within the first 4.5 months (short DLT period). At least one patient must complete the short DLT period before dose escalation. A RT-alone calibration arm aids toxicity attribution. This trial is in progress: CONCORDE-A (olaparib (PARP inhibitor)), CONCORDE-B (AZD1390 (ATM inhibitor)), CONCORDE-C (ceralasertib (ATR inhibitor) followed by consolidation durvalumab+/-ceralasertib) and CONCORDE-E (AZD5305/saruparib (PARP1select inhibitor) followed by consolidation durvalumab) are open to accrual as of 24/11/2023. 57 of 74 registered participants have been randomised across 4 study arms. Of those 57 randomised: 55 started treatment: 20 received RT-alone, 12 received olaparib+RT, 14 received AZD1390+RT, 6 received ceralasertib+RT, 3 received AZD5305+RT and 2 withdrew. CONCORDE continues to recruit to the target sample size of 160 (40/arm) and welcomes further UK centres. A parallel multimodality translational program to identify biomarkers of treatment response, toxicity and the impact on the immune system are in development. Biomarkers of interest include plasma toxicity markers, immune cell profiling, radiomics and ctDNA. Clinical trial information: 10142971.
JCOG2002: A randomized phase III study of thoracic radiotherapy for extensive stage small cell lung cancer.
Authors: Nosaki Kaname , Zenke Yoshitaka , Nomura Shogo , Sasaki Tomonari , Niho Seiji , Yoh Kiyotaka , Yoshioka Hiroshige , Hosomi Yukio , Okamoto Isamu , Kaneda Hiroyasu , Akamatsu Hiroaki , Okamoto Hiroaki , Sasaki Keita , Sekino Yuta , Horinouchi Hidehito , Ohe Yuichiro
Published: June 2024

TPS8132

Background: Consolidative thoracic radiotherapy (cTRT) has shown a marginal improvement in overall survival (OS) and progression-free survival (PFS) for extensive-stage small-cell cancer (ES-SCLC). Consequently, ASTRO and NCCN guidelines conditionally recommend the use of cTRT. Despite the recent establishment of anti-PD-L1 antibody (aPD-L1) combined with platinum-doublet chemotherapy as the standard first-line treatment for ES-SCLC, the impact of cTRT in the era of immunotherapy remains uncertain. Methods: The JCOG2002 study, a randomized, multicenter phase 3 trial, initiated in October 2021 to assess the superiority of additional cTRT in terms of OS for ES-SCLC following induction aPD-L1 plus platinum doublet chemotherapy. Eligibility patients must meet criteria for the first registration including ES-SCLC, no prior radiation or chemotherapy history, age 20 or older, ECOG performance status 0 or 1, and adequate organ function. Induction treatment involves atezolizumab + carboplatin + etoposide or durvalumab + cisplatin / carboplatin + etoposide. Responding patients proceed to the second registration, randomization (1:1 between 30 Gy in 10 fractions of cTRT plus aPD-L1 maintenance therapy and maintenance therapy only). The cTRT targets metastatic lymph nodes in stations #1-7 and ipsilateral stations #10-12 identified at diagnosis. The adjustment factors include response to induction treatment (CR/PR versus SD), presence of brain metastasis (yes versus no), participating institutions, and aPD-L1 type (atezolizumab versus durvalumab). The primary endpoint is OS, with secondary endpoints being PFS and safety. The study aims to enroll 240 randomized patients, with 330 in the first registration, providing 80 % power at a one-sided 5 % significance level to detect a hazard ratio of 0.69 with 3-year accrual period and 1-year follow-up. As of February 6, 2024, 239 patients initiated induction treatment, and 121 have been randomized. This trial is registered at Japan Registry of Clinical Trials as jRCTs031210393 (https://jrct.niph.go.jp/detail/jRCTs031210393). Clinical trial information: jRCTs031210393 .
Effect of measurements on quantum speed limit
Authors: Srivastav Abhay , Pandey Vivek , Pati Arun K.
Published: June 2024

Given the initial and final states of a quantum system, the speed of transportation of state vector in the projective Hilbert space governs the quantum speed limit. Here, we ask the question: what happens to the quantum speed limit under continuous measurement process? We model the continuous measurement process by a non-Hermitian Hamiltonian which keeps the evolution of the system Schrödinger-like even under the process of measurement. Using this specific measurement model, we prove that under continuous measurement, the speed of transportation of a quantum system tends to zero. Interestingly, we also find that for small time scale, there is an enhancement of quantum speed even if the measurement strength is finite. Our findings can have applications in quantum computing and quantum control where dynamics is governed by both unitary and measurement processes.
Broadband characteristics and bandpass acoustic focusing via movable second-order Helmholtz resonator
Authors: Yang Mengchun , Zhao Jinyu , Liu Zihao , Gong Shulei , Liu Yuan , Li Yongchang
Published: June 2024

In this paper, a method is theoretically proposed to obtain a novel movable second-order Helmholtz resonator by adding a perforated plate inside the cavity of the Helmholtz resonator that can be freely tuned up and down. Through software simulation, it is concluded that the resonator meets the design objective of saving production costs so that when the manufactured physical object is required to change the structural parameters, it only needs to be dynamically adjusted on this basis, rather than to reproduce a new physical object with new structural parameters. Meanwhile, it has excellent acoustic characteristics, with a stop band in the range of 80–610 Hz at the low frequency and a bandpass acoustic focusing characteristic in the range of 4050–5250 Hz. It can achieve directional adjustable focus acoustic focusing for plane waves incident at any angle, and directional adjustable focus acoustic focusing for cylindrical wave incidence, with excellent focusing effect. The added perforated plate changes the resonator one-item structure model and can be reused to meet different structural parameters.