bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-world safety and healthcare resource utilization (HCRU) of lurbinectedin (lurbi) in patients (pts) with small cell lung cancer (SCLC): Jazz EMERGE 402 updated analysis.
Authors: Badin Firas Benyamine , Lammers Philip Edward , Patel Mehul P. , Shunyakov Leonid , Slater Dennis , Labbé Catherine , Naveh Navit , Boccuti Anne , Hanvesakul Raj , Li Wenyan , Rengarajan Badri , Halmos Balazs
Published: June 2024

e23266

Background: Lurbi monotherapy received approval in multiple countries, including accelerated US FDA approval and conditional Health Canada approval for adults with metastatic (US) or stage III/metastatic (Canada) SCLC with disease progression on or after platinum-based chemotherapy, based on a phase 2, open-label, single-arm trial (Trigo et al, Lancet Oncol 2020). Jazz EMERGE 402 (NCT04894591) is a phase 4 observational study assessing the effectiveness, safety profile, and HCRU of lurbi in pts with extensive-stage SCLC treated in real-world clinical settings. Here, we report updated safety data and HCRU. Methods: This study is enrolling pts with extensive-stage SCLC treated with lurbi according to the local approved label in the US and Canada. Results: Enrollment is ongoing with a target of 300 pts. Between 28JUN2021 and 27DEC2022, 105 pts were enrolled and followed for ≥6 months after the first dose of lurbi (data cutoff: 27JUN2023). The median (range) age was 67 (44-87) years; 72 (69%) pts had prior immunotherapy; 22 (21%) had an Eastern Cooperative Oncology Group performance status of ≥2; and 25 (24%) had central nervous system involvement. All pts received ≥1 cycle of lurbi; 56 (53%) as second-line (2L) and 37 (35%) as third-line (3L) therapy. The median (range) number of lurbi cycles was 4 (1-31) and the median (range) duration of exposure was 97 (21-694) days. Dose modifications occurred in 27 (26%) pts, with 17 (16%) requiring dose reductions. Granulocyte colony-stimulating factor was administered in 43 (41%) pts (34 [79%] as primary and 7 [16%] as secondary prophylaxis; 2 [5%] were unknown). At the time of data extraction, lurbi treatment was ongoing in 11 (10%) pts and 23 (22%) pts received subsequent anticancer therapy after lurbi. Treatment-related adverse events (TRAEs) were reported in 40 (38%) pts and treatment-related serious adverse events (SAEs) in 13 (12%) pts. The most common TRAEs were anemia (n = 13, 12%), neutropenia (n = 10, 10%), nausea (n = 8, 8%), and fatigue (n = 7, 7%). Thirty-six pts were hospitalized for a median (interquartile range [IQR]) duration of 10 (4, 18) days (Table). No pts were hospitalized on the first day of treatment; 4 pts were hospitalized during the first 21-day cycle. The most common reasons for hospitalization were pneumonia (n = 10, 28%) and sepsis (n = 6, 17%; one was an SAE). Conclusions: In this phase 4 study, lurbi was well tolerated, with low rates of HCRU and a safety profile generally consistent with that reported in the phase 2 trial. Clinical trial information: NCT04894591 . [Table: see text]
Surgical decision-making after neoadjuvant chemotherapy for breast cancer.
Authors: Reddy Haritha , Lopez May Martina , Berkalieva Asem , Moshier Erin , Tsang Ashley Tai
Published: June 2024

e23282

Background: Following neoadjuvant chemotherapy (NAC), a significant subset of breast cancer patients become candidates for breast conserving surgery (BCS) after tumor downstaging. Studies have shown there is no survival advantage between BCS and mastectomy after NAC and that patient prognosis is largely predicted by the pathologic response to treatment. While the literature highlights many aspects of surgical decision-making in breast cancer, there is little analysis of patient choice after NAC. The goal of this study is to investigate clinical and demographic factors that may associate with patients’ surgical decision-making after receiving NAC as well as related outcomes. Methods: A retrospective chart review was conducted on breast cancer patients at our institution who became BCS candidates after receiving NAC from 1/1/2010 to 9/30/2020. Patient demographics, clinical characteristics, choice of mastectomy versus BCS, and outcomes were compared. Exclusion criteria included inflammatory, recurrent, and bilateral breast cancers, and patients with genetic predisposition. T-tests and chi-squared tests of association were used for continuous and categorical variables respectively. Survival outcomes were reported using the log-rank test. The p-value threshold for significance was p < 0.05. Statistical analysis was performed using R software version 4.2.3. Results: In this analysis, 244 patients met study criteria, of which 181 (74.2%) patients chose BCS and 63 (25.8%) patients elected mastectomy. Patients who chose mastectomy were younger at time of diagnosis than those who chose BCS: median age 48 years in mastectomy group versus 53 years in BCS group (p = 0.003). Regarding physical exam findings, while palpability of the primary breast tumor was not associated with choice of surgery (p = 0.271), presence of axillary lymphadenopathy was associated with a higher likelihood of choosing mastectomy (44.4% in mastectomy subgroup versus 29.3% in BCS subgroup, p = 0.041). Patient race, pre-treatment clinical stage, and doxorubicin-based chemotherapy were not associated with patients’ decisions for type of surgery. With respect to outcomes, follow-up time was similar between both groups with overall median of 5 years, and there was no significant difference in local or distant recurrence, and overall mortality (log-rank p = 0.3). Conclusions: The majority of breast cancer patients elect BCS after downstaging from NAC. Factors that are associated with choosing mastectomy include younger age at diagnosis and pre-treatment palpable axillary lymphadenopathy, which may be perceived as more advanced stage, despite no difference in stage between both groups. Regardless of surgical choice, both recurrence and mortality rates did not significantly differ between patients who chose BCS versus mastectomy, which is consistent with the literature.
Cancer burden across South Asia in 2020: A global cancer observatory analysis.
Authors: Jain Urvish , Rahim Faraan , Jain Bhav , Arkalgud Aditya , Sabat Cameron , Hammond Alessandro , Tshering Phub , Patel Tej A. , Sirohi Bhawna , Jain Pankaj , Zeb Khan Shah , Gunasekera Sanjeeva , Shilpakar Ramila , Stanikzai Zabihullah , Chowdhury Arman Reza , Swami Nishwant , Dee Edward Christopher Christopher , Gyawali Bishal
Published: June 2024

e23292

Background: The cancer burden in South Asia is often associated with late diagnosis and poor outcomes because of barriers to accessing advanced treatment facilities and targeted therapies, financial sequelae of care, and cultural stigmas and misconceptions. We use recent estimates of the Global Cancer Observatory (GCO) to better understand the epidemiology of cancer in South Asia, which may inform national and regional cancer control. Methods: Using publicly available data from the GCO and the World Bank, we collected cancer statistics and population statistics for Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka (collectively, SAARC) from 2015-2020. Results: The crude incidence of cancer in this region was 1,733,573 cases, representing 9.0% of the incidence worldwide. The crude incidence rate (CIR, per 100,000) of cancer in SAARC was 93.4 compared to the worldwide rate of 247.5. The 5-year prevalence (in total cases) of cancer in South Asia was 3,474,184, compared to 50,550,287 globally. The crude mortality rate (CMR, per 100,000) in South Asia was 60.6, compared to 127.8 globally. However, the mortality-to-incidence ratio (MIR) (per 100,000) was 0.65, compared to 0.52 globally. Age-adjusted estimates are reported in the table. Conclusions: Our research highlights South Asia's unique cancer landscape with CIR and MIR, but elevated MIR compared to global figures. These findings underscore the need for a united, contextually relevant approach to addressing the burden of cancer in South Asia. Investment in collaborative, tailored cancer care programs will build the SAARC region's capacity to address the growing global cancer challenge. [Table: see text]
Juxtacortical chondrosarcoma: An NCDB analysis of demographics and socioeconomic factors.
Authors: Peterson Michael , Tade Yanick , Lopez Braden M. , Tandon Nikhita , Silberstein Peter T. , Heise Craig , Hsia Beau
Published: June 2024

e23505

Background: Juxtacortical chondrosarcoma (JCC) is a rare cartilaginous tumor—accounting for less than 2% of all chondrosarcomas—and typically appears on the external surfaces of long bones. The prognosis of JCC is relatively promising compared to other chondrosarcomas, with the current therapy of choice being en-bloc resection. However, a significant amount of information regarding JCC remains unknown. Therefore, exploring diagnostic trends may provide greater insight into this cancer’s epidemiology and potential forms of treatment. The National Cancer Database (NCDB) was assessed to uncover the demographic factors in patients diagnosed with JCC. Methods: A retrospective cohort analysis utilizing the 2004–2020 National Cancer Database (NCDB) included 131 subjects with a histologically-confirmed diagnosis of JCC (ICD-0-3 code 9221). Demographic factors (age, sex, race, Hispanic status, insurance status, facility type, distance from facility, and Charleson-Deyo comorbidity score) were analyzed by descriptive statistics and incidence trends were interpreted in regression analysis. Results: Between 2004 and 2020, the NCDB reported a total of 131 patients with a confirmed diagnosis of JCC. This data indicated a rising incidence of patients diagnosed per year (R² = 0.0855), with an average age of diagnosis of 45 years (SD = 18, range = 8-88). Patients with JCC were more likely to be White (82%), of non-Hispanic origin (86%), and male (63%). The tumor was most commonly found in the long bones of the lower limbs (35%). Surgical removal was the primary treatment for the majority of patients (95%), while others received radiation (7%) or chemotherapy (4%). Most patients (83%) had a Charlson-Deyo comorbidity score of 0. Patients were commonly treated at academic and research facilities (61%), and no patients received palliative care. More than half of individuals were privately insured (57%) and resided in a metropolitan area with a population size of at least 1 million (59%). The mean distance between patient residence and treatment site was 104.1 miles (SD = 221, range = 11-1194 miles). Conclusions: To the best of our knowledge, this is the first study on juxtacortical chondrosarcoma utilizing NCDB data to address the significant lack of research on this subject. The majority of JCC patients are non-Hispanic, White, and have a primary site of diagnosis at the long bones of the lower limbs. This paper is the first to describe the socioeconomic factors of patients diagnosed with JCC: patients tend to be privately insured, live in large metropolitan areas, and are mostly treated in academic research facilities. Additional research is necessary to comprehend how socioeconomic and demographic factors influence the manner in which JCC patients are diagnosed and treated.
Place of rank ligand inhibitor in giant cell tumour of bone.
Authors: Kerboua Esma
Published: June 2024

e23511

Background: Giant cell tumour of bone (GCTB) is a locally aggressive and osteolytic tumour.The peak incidence is during the third and fourth decades of life. The majority of tumours occur in the metaepiphyseal (end) region of the long bones. Surgical resection is the preferred treatment option, if possible but it is a tumor which always poses progressive problems. Denosumab is indicated in recurrent or unresectable GCTB. Methods: We report a series of 70 patients treated for GCT at the medical oncology department of the CPMC (Algiers) in collaboration with the orthopedics department of Mustapha University Hospital from January 2020 to December 2023. Results: 70 patients ( 50 women and 20 men). The sex ratio is 0.54 The average age is 22 years (11-54 years). Reason for consultation : - Pathological fracture: n = 10 - Pain: n = 30 - Functional impotence: n = 20 - Tumor mass: n = 5 - Concept of trauma: n = 5 Stage of the disease: -Localized: n = 29 -Recurrence: n = 30, -Recurrence + pulmonary metastases: n = 10, -Sarcomatous transformation: n = 1 Type of treatment: -Radiotherapy, n = 1 -Exercised biopsy: n = 10, -Curettage + cementoplasty: n = 50 -Exeresis with osteosynthesis material: n = 8, -Amputation : n = 1 Medical treatment: Denosumab: n = 45 The number of courses with denosumab was between 6 and 55 cycles. Denosumab was administered neoadjuvantly in 10 patients, in 20 patients with reccurence disease, 15 patients in the metastatic phase - In terms of toxicity, we noted moderate hypocalcemia in 3 patients. -Objective responses: 95% ORR, 5 complete radiological responses and 10 partial responses, 20 stable patients and 9 out of 10 patients who received neoadjuvant denosumab were able to operate.Progression Free Survival was 28 months. Conclusions: GCTs are aggressive tumors with intermediate malignancy that should not be underestimated. The treatment is essentially surgical. Denosumab is indicated for both neoadjuvant and adjuvant use, it allows obtaining a clear clinical and radiological improvement.
Procollagen C-protein enhancer 1 (PCPE-1) as a potential serum biomarker for osteosarcoma.
Authors: Strauss Gal Zvi , Halperin Sharon , Appel Sarit , Sheiman Avivit , Weitzen Rony , Ben Gal Ofir , Liberman Boaz , Ramu Eyal , Ben Ami Eytan Aharon
Published: June 2024

e23518

Background: Osteosarcoma (OS) is the most common bone malignancy in children and young adults. Treatment with perioperative systemic chemotherapy has improved patient outcome but a third of patients will eventually develop incurable metastatic disease. Currently, there are no biomarkers for monitoring patients’ response to neo-adjuvant (NA) chemotherapy or for patients under active surveillance following treatments. Procollagen C-Proteinase Enhancer-1 (PCPE-1) is an extra-cellular matrix glycoprotein which promotes the maturation of pro-collagen into collagen in various tissues. Elevated serum levels of PCPE-1 are found in bone diseases such as Paget’s disease and Osteoporosis and in patients with breast cancer with bone metastases. Serum PCPE-1 has not been described in patients with OS. We aimed to describe PCPE-1 serum levels in patients with OS compared with healthy volunteers, and across different time points in their treatment and disease course. Methods: We collected serum samples from the Israeli national biobank of 18 adult OS patients. Serum samples were also collected from 6 healthy individuals. Additionally, we obtained serial samples from 4 OS patients prior to and after initiating NA therapy. Quantification of serum PCPE-1 levels was performed using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. Results: We successfully analyzed serum PCPE-1 levels from all patients and healthy volunteers. Mean PCPE-1 levels of 553ng/ml (range 479-614ng/ml) were observed in OS patients, compared with 313ng/ml (285-339ng/ml) in healthy volunteers. Of 4 patients undergoing treatment who had serial samples, a decrease in serum levels was observed 2 responding patients, while an increase in PCPE-1 levels were observed in one patient after NA treatment who had no response to treatment at the time of surgery. Of notice, serum levels nearly doubled in a patient during active surveillance who experienced local disease recurrence (274ng/ml and 423ng/ml, respectively). Conclusions: This is the first study to show elevated PCPE-1 serum levels in patients with OS. Our study also demonstrates potential changes in PCPE-1 levels in response to treatment. We are expanding our study to include a pediatric population to investigate the role of PCPE-1 as a potential tumor biomarker for monitoring treatment and surveillance of OS.
Overall survival in soft tissue sarcomas (STS) in Hispanic vs non-Hispanic White patients: Single center experience.
Authors: Zamora DIana , Ikram Waleed , Braat Jonathan , Dinh Han , Azevedo Chelsea , Patel Shyamal , Wiseman Jason T. , Gonzalez Velez Miguel
Published: June 2024

e23526

Background: Racial, ethnic, and socioeconomic factors have been implicated in the variability of survival rates among soft tissue sarcoma (STS). These disparities are multifactorial and may reflect differences in disease biology, access to care, treatment responses, and others. In situations where different racial groups have equitable access to healthcare, healthcare disparities can decrease, and survival gaps can narrow. Differences in survival in STS in racial minorities have been poorly studied. Recognizing the potential impact of such disparities, our study thereby contributes to the ongoing discourse on healthcare equity in STS outcomes. Methods: We conducted a retrospective analysis of 30 STS patients, stratifying them into Hispanic (H) and non-Hispanic white (NHW) groups at Dignity Health Cancer Institute in Phoenix, Arizona. The Mann-Whitney U test was chosen to compare survival distributions, given the non-normal distribution of our sample. Survival analysis was performed using the Kaplan-Meier method, and the log-rank test was applied to determine statistical significance. All analyses were executed in GraphPad Prism software. Results: Our cohort comprised 13 (43%) NHW and 17 (57%) H patients. The mean ages were 57.2 years for NHW and 48.9 years for H, with a balanced gender distribution across groups. The most common subtypes of STS in NHW were liposarcoma (n = 3, 23.1%), and spindle cell carcinoma (n = 2,15.4%). Comparatively, the most common subtypes of STS in H were liposarcoma (n = 5, 29.4%) and leiomyosarcoma (n = 3, 17.6%). All patients were diagnosed with Stage 4 STS. Treatment modalities differed marginally, with NHW patients undergoing more surgical interventions, while H patients were more frequently administered chemotherapy. Median overall survival from the start of first-line therapy was 412 days for NHW and 500 days for H patients. Despite the longer median overall survival observed in Hispanics, the intergroup difference did not reach statistical significance (P = 0.68). Conclusions: The similar survival times between H and NHW STS patients at our institution may hint at an equitable provision of care across racial demographics in a relatively controlled single-center experience. However, the trend of extended survival in the Hispanic group, while not statistically confirmed, raises questions that merit further inquiry. This study serves as a preliminary exploration into racial disparities in STS, advocating for larger-scale research with more diverse patient populations. Further studies are essential to understand these findings and identify and optimize factors contributing to narrowing the survival gap in minorities, with the goal of enhancing STS prognosis for all racial groups.
Clinical efficacy and safety of mTOR inhibitor in patients with advanced unresectable epithelioid hemangioendothelioma (EHE).
Authors: Tan Huijing , Sun Yuting , Chi Yihebali
Published: June 2024

e23540

Background: Epithelioidhemangioendothelioma is a rare vascular soft tissue sarcoma, 90% of which contains WWTR1-CAMTA1 fusion gene. Studies have shown that mTOR inhibitors may have a certain effect on EHE patients. Methods: A retrospective analysis of the efficacy and safety of mTOR inhibitor everolimus in the treatment of advanced unresectable epithelioidhemangioendothelioma in our hospital in the past one year. Patients with advanced epithelioidhemangioendothelioma (EHE) confirmed by consultation in the pathological center received this regimen, everolimus 10mg, once a day orally for 28 days, every 4 weeks as a treatment cycle until the disease progressed or showed intolerable toxicity. Results: There were 3 females and 5 males, and their average age was 41.8 years old. All of them were unresectable with liver, lung, and shoulder primary lesions, and lungs, liver, pleura and bone metastasis. Ki67 is from 2% to 10%. 3 patients who received molecular pathological examination were all identified the WWTR1-CAMTA1 fusion gene, and one of them also had EWSR1 chromosome translocation. Previous antineoplastic treatments included gemcitabine, cisplatin, albumin paclitaxel, epirubicin, dacarbazine chemotherapy, anlotinib targeting, and toripalimab immune therapy. 5 patients were treated with first-line drugs, 2 cases with second-line and 1 case with third-line. In terms of overall efficacy, 1 case was not evaluated, 2 cases lost follow-up due to poor tolerance and economic factors, 2 cases were included in the clinical trails after reaching tumor control for 3 months, and the other 3 cases achieved tumor remission with a median PFS of 11.0 months, and the best curative effect was SDa. Severe oral mucositis can greatly affect the medication experience of patients, which can be relieved after symptomatic medication, or when interstitial pneumonia and hemogram decrease significantly, we can consider the oral administration of everolimus 5mg. Conclusions: At present, there is no standard treatment for EHE, we can roughly see the efficacy of mTOR inhibitor everolimus in some EHE patients, mainly disease stability. Emphasis on side effect management, improve tolerance, and systematic treatment of EHE needs to be further explored.
Malignant mesenchymoma: A demographic analysis of the National Cancer Database.
Authors: Alban Sierra , Moroz Mark , Grover Jasika , Chin Kat , Silberstein Peter T. , Heise Craig , Hsia Beau
Published: June 2024

e23556

Background: Malignant mesenchymoma is a rare, aggressive soft tissue tumor characterized by the presence of two or more histologic subtypes of sarcoma. As a result of these characteristics, this cancer has a poor prognosis and a lack of proven treatment options. It may be epidemiologically beneficial to analyze the diagnostic trends to further understand the factors contributing to the disease. This study examines the demographic factors of malignant mesenchymoma, ICD-O-3 Code 8990, through the National Cancer Database (NCDB). Methods: The 2004-2020 NCDB was used for retrospective analysis. 72 patients were identified and their demographic factors such as age, sex, race, Hispanic status, educational attainment, insurance status, facility type and location, distance from facility, and Charlson-Deyo score were analyzed using descriptive statistics. Regression analysis was used to interpret incidence trends. Results: The NCDB contains 72 recorded cases of malignant mesenchymoma from 2004-2020 with an average age at diagnosis of 49.9 ± 21.3 years, with the incidence rate exhibiting variability (R2= 0.1028). Women had a considerably higher diagnosis rate (67%) compared to men (33%). The majority of patients were White (75%), and 11% of patients were Black. Most patients were of non-Hispanic origin (81%). A higher percentage of patients fell into the fourth quartile of income earners (32%) compared to the top three quartiles. A significant portion of patients (26%) did not have a high school degree. The sites with the highest cancer prevalence were the retroperitoneum (10%) and endometrium (10%). A majority of individuals (78%) had Charlson-Deyo comorbidity scores of 0. The size of the tumors ranged from 10.0 to 250.0 mm with an average size of 61.6 ± 67.4 mm. A majority of the patients (72%) underwent surgery at the primary site. Most (96%) patients survived at least thirty days following their primary surgery, with 94% surviving for ninety or more days. The mean survival time was 91.0 months. The cancer’s 2-year, 5-year, and 10-year survival rates were 61.5%, 45.5%, and 43.1% respectively. Conclusions: Based on our searches, this is the first NCDB study on malignant mesenchymoma to address epidemiological gaps in the literature. Most malignant mesenchymoma patients identified as non-Hispanic and White with a primary site of either the retroperitoneum or endometrium. The majority of patients fell into the fourth income quartile, and a significant amount did not have a high school degree. Due to this cancer’s rarity, recent literature exploring the factors contributing to the disease course is scarce. Additional research is necessary to understand how demographics influence the diagnosis, treatment, and long-term outcomes of individuals diagnosed with malignant mesenchymoma.
Epidemiological trends and socioeconomic factors in malignant peripheral nerve sheath tumors with rhabdomyoblastic differentiation: A National Cancer Database study.
Authors: Diagne Yaye Fatou , Brausch William , Chin Kat , Langas Isabel , Silberstein Peter T. , Heise Craig , Hsia Beau
Published: June 2024

e23562

Background: Malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation, also called a malignant triton tumor (MTT) is both a rare and aggressive form of cancer with both the features of peripheral nerve sheath tumors as well as rhabdomyoblasts with high recurrence rates. There is a higher risk of patients with neurofibromatosis type 1 (NF1) developing MTT. Radiation can be used to excise higher grade large MTT, however, chemotherapy still has no consensus on efficacy. Despite the rarity of MTT with rhabdomyoblastic differentiation, increased efforts to understand epidemiological trends could increase overall understanding of the malignancy. Methods: We extracted data from 50 patients diagnosed with MTT(ICD-9561-3) using the 2004-2020 National Cancer Database (NCDB) to perform a retrospective cohort analysis. We focused on various demographic factors including age, sex, race, Hispanic status, income status, educational status, insurance status, facility type and location, distance from facility, and Charleson-Deyo score using descriptive statistics. Regression analysis was used to identify incidence trends. Results: In our study of 50 patients diagnosed with MTT, a majority of the patients were male (62%), identified as White, and were of non-Spanish/non-Hispanic (90%) ethnicity. The average age at diagnosis was 49 years (SD = 20, range = 3-90) most and patients were treated in academic/research facilities (32%) or integrated network cancer programs (18%). Most patients (48%) had private insurance, with a significant number relying on government-funded programs (44%). The majority of patients (88%) underwent surgery as their primary treatment, with 30% having no residual tumor post-surgery. Additional treatments included radiation therapy (38%), chemotherapy (34%) and the most frequent primary site was the retroperitoneum (30%).The average survival time post-treatment was 35 months, with a survival rate of 43% at 2 years, 23% at 5 years, and a 15% at 10 years. Patients qualified for the top quartile of median housing income( $74,063 ≈). Conclusions: This study is the first analysis of patients with MTT, using the NCDB. It fills a gap in our understanding of this rare and aggressive disease. The majority of MTT patients were male, Caucasian, with an average age at diagnosis of 49 years, which supports previous case report descriptions. In addition, this study reveals the socio-economic factors associated with these patients who mostly earned a median income of $74,063 or more, were insured primarily by private insurance or managed programs (48%), and were treated predominantly in academic or research institutions (32%). It is necessary to continue research to further understand the influence of demographic and socio-economic factors on the diagnosis, treatments, and overall survival of patients with MTT.
A phase I/II trial of neoadjuvant pegylated arginine deiminase (ADI-PEG 20) with ifosfamide and radiotherapy in soft tissue sarcomas (STS) of the trunk or extremity.
Authors: Weiss Mia C. , Haarberg Sasha , Luo Chongliang , Hirbe Angela C. , Apicelli Anthony J. , English D. Ian , Van Tine Brian Andrew
Published: June 2024

TPS11591

Background: Outcomes for the treatment of metastatic STS remain poor. Better therapies are needed for local and distant control. Arginine is essential to neoplastic growth, yet up to 88% of STS do not express argininosuccinate synthetase (ASS1), an enzyme necessary to produce arginine. ADI-PEG 20 is a microbial enzyme that degrades arginine causing auxotrophy in cancer cells that are ASS1 negative. Pre-clinical data demonstrates that arginine deprivation shunts glutamine towards oxidation via the TCA cycle, thus depleting glutathione stores and increasing oxidative stress to the cell. We hypothesize that the combination of ADI-PEG 20, ifosfamide, and radiation therapy can potentiate cellular death. The encouraging safety and clinical data from the ADI-PEG 20 + radiation + temozolomide trial (NCT04587830) further support this combination. We are conducting a phase I/II trial examining the safety and tolerability to determine the recommended phase II dose (R2PD) and evaluate the efficacy of ADI-PEG 20 in combination with ifosfamide and radiation in patients with high-grade STS. Methods: Eligible patients include untreated intermediate or high-grade extremity or truncal STS planned for definitive resection with performance status 0-1 and adequate organ function. Metastatic disease is exclusionary as well as receiving prior treatment for the study cancer. The total number of patients to be enrolled is approximately 35. Up to 15 patients will be enrolled in the phase I portion with a 3 + 3 dose escalation design with ADI-PEG 20 in combination with escalating doses of ifosfamide and radiation. The primary objectives include determining safety and tolerability as well as the recommended phase II dose (RP2D). Patients will be treated neoadjuvantly with ADI-PEG 20 dosed once weekly starting on Cycle 1 Day -7 with ifosfamide for up to three cycles in combination with standard radiotherapy given over approximately 5 weeks. Ifosfamide will be administered on Days 1 - 5 of all 3 cycles. The phase II participants will receive the combination with ifosfamide at the RP2D determined during phase I. The primary objective of the phase II portion is to determine the percent necrosis and pathologic complete response (pCR) at the time of resection. These endpoints will be summarized by proportions along with the associated 2-sided exact 95% CIs. Assuming the true pCR rate is 25%, enrolling 20 patients will result in a 90% CI for estimating the pCR (10%, 45%). The trial has begun accrual and is soon to open at multiple sites. Clinical trial information: NCT05813327 .
Traumatic Brain Injury and Traumatic Spinal Cord Injury
Authors: Podell Jamie E. , Morris Nicholas A.
Published: June 2024

OBJECTIVE

This article reviews the mechanisms of primary traumatic injury to the brain and spinal cord, with an emphasis on grading severity, identifying surgical indications, anticipating complications, and managing secondary injury.

LATEST DEVELOPMENTS

Serum biomarkers have emerged for clinical decision making and prognosis after traumatic injury. Cortical spreading depolarization has been identified as a potentially modifiable mechanism of secondary injury after traumatic brain injury. Innovative methods to detect covert consciousness may inform prognosis and enrich future studies of coma recovery. The time-sensitive nature of spinal decompression is being elucidated.

ESSENTIAL POINTS

Proven management strategies for patients with severe neurotrauma in the intensive care unit include surgical decompression when appropriate, the optimization of perfusion, and the anticipation and treatment of complications. Despite validated models, predicting outcomes after traumatic brain injury remains challenging, requiring prognostic humility and a model of shared decision making with surrogate decision makers to establish care goals. Penetrating injuries, especially gunshot wounds, are often devastating and require public health and policy approaches that target prevention.
In vitro and in vivo metabolic studies of dietary flavan-3-ols
Authors: Στουπή Σταυρούλα
Published: June 2024

Ο μεταβολισμός της εντερικής μικροχλωρίδας επιλεγμένων διατροφικών φλαβαν-3-ολών ερευνήθηκε χρησιμοποιώντας ένα στατικό μοντέλο καλλιέργειας in vitro. Καθαρή προκυανιδίνη B2 και το σχετιζόμενο μονομερές της, (-)-επικατεχίνη, παρήγαγαν μια σειρά από φαινολικές και φαινυλοκαρβοξυλικές παράγωγες ενώσεις. Οι πιο άφθονες ήταν μονο- και διυδροξυλιωμένες φαινυλοπροπαν-2-όλες, μονο- και διυδροξυλιωμένες φαινυλοβαλερολακτόνες, ένα μονοϋδροξυλιωμένο βαλερικό οξύ, ένα μονοϋδροξυλιωμένο προπιονικό οξύ και ένα φαινυλοξεικό οξύ. Παρουσιάζονται αποδείξεις για την παραγωγή νέων μεταβολιτών από την προκυανιδίνη B2, οι οποίοι διατηρούν τον δακτύλιο A του φλαβανόλης και τον δεσμό C4-->C8 μεταξύ των φλαβανών, συμπεριλαμβανομένων κάποιων με συγκριτικά μεγάλη μάζα (Mr ≥ 290) που διατηρούν τη ‘διμερική’ φύση του υποστρώματος. Επιβεβαιώθηκε ότι ο μικροβιακός μεταβολισμός προτιμούσε την αποϋδροξυλίωση στη θέση 4’- παρά στη 3’-, και και ότι έλαβαν χώρα τόσο α- όσο και β-οξείδωση.Ο μεταβολισμός in vitro της (+)-κατεχίνης και της (-)-επιγαλλοκατεχίνης από την ανθρώπινη εντερική μικροχλωρίδα παρήγαγε λιγότερους μεταβολίτες από ότι η (-)-επικατεχίνη ή η προκυανιδίνη B2. Ο μεταβολισμός in vitro ακατέργαστων εκχυλισμάτων μαύρου τσαγιού, θεαφλαβινών (TFs) και θεαρουβιγινών (TRs), δεν παρήγαγε ανιχνεύσιμους μικροβιακούς μεταβολίτες. Μελέτες χρησιμοποιώντας κυτταρικές καλλιέργειες έδειξαν ότι το 3-(3’-υδροξυφαινυλο) προπιονικό οξύ απορροφήθηκε, παρόμοια με, αλλά σημαντικά πιο αργά (P ≤ 0.05) από το φερουλικό οξύ. Και οι δύο ενώσεις απορροφήθηκαν μέσω παθητικής διακυτταρικής μεταφοράς. Το 3-(3’-υδροξυφαινυλο) προπιονικό οξύ διαπέρασε με την ελεύθερη, μη συζευγμένη μορφή του, υποδεικνύοντας ότι είναι ένας δυνητικά χρήσιμος βιοδείκτης για την εξέταση των ευεργετικών επιδράσεων στην υγεία. Χορηγώντας σε αρουραίους ενδοφλεβίως και από του στόματος [14C] προκυανιδίνη B2, καθορίστηκαν οι φαρμακοκινητικές παράμετροι για το [14C]. Αποδείχθηκε ότι ένα μεγάλο κλάσμα της δόσης της μητρικής ένωσης που χορηγήθηκε από του στόματος, διασπάστηκε σε διάφορες χημικές ενώσεις από την εντερική μικροχλωρίδα πριν από την απορρόφηση στη συστηματική κυκλοφορία.
Equivalent Notions in the context of compatible Endo-Lie Algebras
Authors: Azizi Elmostafa
Published: June 2024

In this article, we introduce a notion of compatibility between two Endo-Lie algebras defined on the same linear space. Compatibility means that any linear combination of the two structures always induces a new Endo-Lie algebras structure. In this case of compatibility, we show that the notions of bialgebras, standard Manin triples and matched pairs are equivalent. We find this equivalence for the case of compatible Lie algebras since this is a particular case of compatible Endo-Lie algebras.
Digital Solutions In Children'S Services
Authors: Hayes Derren
Published: June 2024

Digital technology has the potential to change the way children's services departments function, offering opportunities for more efficient working, but also concerns over the safe and ethical use of people's data
Regional adoption agencies
Authors: Stephenson Jo
Published: June 2024

Regional adoption agencies now provide the majority of England's adoption services on behalf of local authorities. Jo Stephenson looks at some of the main findings from Ofsted's sample inspections
Coaches support young people to find stability
Authors: JóŹwiak Gabriella
Published: June 2024

Settle's personal advisers give care-experienced young adults the practical and emotional support they need to successfully transition to independent living
Lewisham Council
Authors: Hayes Derren
Published: June 2024

Inner London borough develops targeted early help offer to reduce demand in children's social care and improve services
On the ‘Production of Life’ and Labour of Care
Authors: Masquelier Charles
Published: June 2024

This chapter both further clarifies what the economic model drawn in the preceding chapter entails and provides utopian insights beyond those making up economic life. It starts by exposing the central role played by the sexual division of labour between production and reproduction in capitalist domination. More specifically, it shows that the separation of society into a private sphere of domesticity and public sphere of work is itself underpinned by divisive and hierarchizing binaries around which capitalist domination operates. Then, the task of envisioning an alternative to this division of labour is undertaken. Maria Mies’ (2014a) notion of ‘production of immediate life’ is shown to be central in understanding how to affirm the radical interdependence between production and reproduction in the dialogically coordinated allocation of resources. The chapter ends with insights into alternative kin relations that such a new relationship between production and reproduction paves the way for. Overall, this chapter aims to show that in order to move beyond the production/reproduction split marking capitalist domination, one must not only institutionalize caring practices within material production, but also treat reproductive life as a form of labour akin to the labour of care imagined in productive life.
Tainted Love: Intimate Relationships and Gendered Violence On-Road
Authors: Bakkali Yusef , Chigbo Ezimma
Published: June 2024

This chapter focuses on the emotional lives of men and women who have lived in proximity to road life. Through using a situated approach, the chapter examines narratives of love and marginality for those at the margins. The chapter examines accounts of how both young men and women became involved in road life, arguing that while the roads are a gendered space, both groups’ involvement involved a level of proximity and long-standing spatial/cultural/familial proximity to the roads as a relational space. The chapter deals with testimonies of relationships, intimacy and domestic life. Gendered struggles around intimacy clearly amalgamate into the everyday hardships of the munpain, as stories of tainted love, abuse and deep emotional turmoil come to the fore. These stories also reveal instances where agency and resistance take place among young women navigating an often antagonistic, male-dominated environment, as well stories of compassion, familial support and care. The chapter highlights important issues around gender, domestic violence and vulnerability, while also offering human perspective on the lives of a group who are often misunderstood, misrepresented and pathologised.
New Directions Please! Veganising Green Criminology
Authors: Peggs Kay
Published: June 2024

This chapter is written from the philosophical perspective of ethical veganism, which opposes speciesism and the commodity status of nonhuman animals. Through this lens, the chapter offers a critical consideration of gendering green criminology by drawing in issues associated with species and human–nonhuman animal entanglements. Although some green criminologists have overlooked or marginalised the position of nonhuman animals, green criminology can encourage thinking about the human exploitation of nonhuman animals. As well, criminology that is not ‘green’ has the tools and perspectives to study more effectively harms and crimes to all species. Drawing on early feminist criminological thought and by embracing a non-speciesist intersectional approach, this chapter concludes with a call to veganise green criminology via activism, with the aim of making a better world.
Men and the Climate Crisis: Why Masculinities Matter for Green Criminology
Authors: Burrell Stephen R.
Published: June 2024

The gendered dynamics of the climate crisis are becoming more widely recognised. However, this has primarily been in relation to how women are being disproportionately impacted; there has been less discussion about the disproportionate role that men and masculinities play in contributing to it – something which is of much relevance to green criminology. For example, on average men have larger carbon footprints than women, express less concern about climate change, and are more likely to work in the most environmentally destructive industries. The socioeconomic systems which have brought about the climate crisis, as well as the meagre policy responses to it to date, have been led predominantly by men, and influenced substantially by masculinist logics. Indeed, as with other forms of environmental harm, global heating can be seen as closely connected to forms of men’s violence. Yet it should also be recognised that some men contribute to climate change much more than others (such as wealthy men in the Global North), and many also practice care for the environment. This chapter will provide an overview of why critical studies on men and masculinities should be central to green criminology and to understanding and tackling the ecocide that is global heating.
Reconceptualising Gendered Dimensions of Illegal Wildlife Trade in Sub-Saharan Africa through Legal, Policy and Programmatic Means
Authors: Agu Helen U. , Ogbuka Josiah C. , Gore Meredith L.
Published: June 2024

This chapter considers the gendered dimension of illegal wildlife trade (IWT) in sub-Saharan Africa in the context of the existing regional and national wildlife legal frameworks, policies, and programmes. This context assisted us to explore the potentials of reconceptualising gender-driven wildlife management interventions in the region and member states. We applied critical review and analyses of existing literatures, legal and policy documents to enable synthesis of available studies on gender in IWT. We also considered the integration of gender-receptive strategies for mainstreaming gendered motivations in wildlife legal frameworks, policies and programmes in the sub-Saharan African region. We recommend the integration of legal, policy and programmatic dimensions into wildlife conservation and management systems in sub-Saharan Africa to assist in addressing the various gendered motivations for wildlife trafficking. This contribution can assist other wildlife-dependent regions and nations in streamlining their wildlife legal frameworks, regulations, policies and programmes to reflect gendered differentiations to IWT in order to drastically minimise or eliminate the rising rate of illegal wildlife practices and networks at global, regional, national and local scales.
Individual Linking Pins and the Life Cycle of Inter-Organizational Cooperation
Authors: Joachim Jutta , Schneiker Andrea
Published: June 2024

The chapter deals with the role individuals play in formalizing security cooperation among humanitarian non-governmental organizations (NGOs). Focusing on the European Interagency Security Forum, it brings together a concept from organizational studies – an understanding of exposed individuals with managing skills as linking pins – with the organizational life cycle from public administration studies. Based on interviews, theoretical literature, policy documents and reports on humanitarian security, linking pins are held to take five specific roles in three specific phases of cooperative relations. Linking pins serve as boundary spanners and entrepreneurs in the start-up phase of security cooperation between NGOs; as purposive practitioners and caretakers in the expansion phase and as gatekeepers in the consolidation phase. It is crucial for NGOs that the same person takes these roles to facilitate cooperation and maintain institutional memory. Fluctuation on this position is problematic as it forces NGOs to adjust to someone new.
Spain: How to Overcome the Polarization about the Conflicts of the Past?
Authors: Zupančič Rok , Kočan Faris , Andresen Kenneth , Bojarska Katarzyna , Dacosta Ricardo , Farrell Seamus , Fiedler Anke , Hoxha Abit , Ioannidis Nikandros , Kirk Niamh , Martín Irene , Milioni Dimitra L. , Panos Dionysis , Paradés Marta , Rawski Tomasz , Triga Vasiliki , Vučko Tjaša
Published: June 2024

This chapter gives a detailed historic overview of the multiple ‘cleavages’ and conflicts that divided the Spanish society. It deals with the process of Spanish transition from dictatorship to democracy after the death of General Franco. It deals with questions of remembrance and how Spanish authorities and politicians dealt with the transition. The chapter also considers several judicial and political decisions that were made until 2020. The first part of the chapter ends with an overview of the new Bill on Democratic Memory. After the short description of a methodology the European Union’s approach to the troubled past in Spain is considered. The chapter ends with policy recommendations in four topical areas.
Poland: Strategies for Challenging the Growing Dominance of Right-wing Memory Politics
Authors: Zupančič Rok , Kočan Faris , Andresen Kenneth , Bojarska Katarzyna , Dacosta Ricardo , Farrell Seamus , Fiedler Anke , Hoxha Abit , Ioannidis Nikandros , Kirk Niamh , Martín Irene , Milioni Dimitra L. , Panos Dionysis , Paradés Marta , Rawski Tomasz , Triga Vasiliki , Vučko Tjaša
Published: June 2024

This chapter starts with overview of some of the episodes from the Polish troubled past and analyses their effects in the present. It deals with two dominant competing trends/narratives in Poland’s memory politics: the so-called ‘pedagogy of shame’ versus the so-called ‘patriotic pride’. This chapter also discusses Polish memory politics regarding the Second World War and the communist past, namely the perspective where the Polish nation is a double victim – of fascism on the one hand and of communism on the other. After the methodology section, where the selection of interviewees is explained, follows the section that reconstructs the European Union’s approach to the troubled past in post-1989 Poland. This approach is divided into four main phases: the 1990s; the period 2000–4; the period 2005–15; and the post-2015 period. The chapter ends with policy recommendations for Poland in four thematic areas.
The European Union
Authors: Zupančič Rok , Kočan Faris , Andresen Kenneth , Bojarska Katarzyna , Dacosta Ricardo , Farrell Seamus , Fiedler Anke , Hoxha Abit , Ioannidis Nikandros , Kirk Niamh , Martín Irene , Milioni Dimitra L. , Panos Dionysis , Paradés Marta , Rawski Tomasz , Triga Vasiliki , Vučko Tjaša
Published: June 2024

This chapter aims to prepare a concrete roadmap for the European Union (EU) in its attempts to find strategies for overcoming troubled pasts in European countries in four different domains that are the same in all chapters (history, media, politics, arts and culture). By doing this, this chapter attempts to answer what the EU institutions can do to help European countries, both members and aspiring candidates for the membership, to foster the processes that would lead to the overcoming of troubled pasts in respective countries. It starts with a short overview of the EU integration processes since the end of the Second World War until the present day, explained from the perspective of the ‘peace ideas’ that have been underpinning integration efforts in different times. Then it analyses the interviews with stakeholders and policy makers on the EU’s approach to troubled pasts. In the end it gives policy recommendations that present a basis for earlier mentioned roadmap for the EU, namely, what the EU could do to assist its member states and the prospective members to overcome the troubled pasts.