bluuebunny/crossref_metadata_2025 huggingface dataset:
Antioxidant activity and phenolic content of herbal infusions from medicinal plants used in Argentina
Authors: Gallia María Celeste , Ferrari Ana , Bajda Leonardo , Bongiovanni Guillermina Azucena
Published: July 2024

Currently, teas and herbal infusions represent an important part of the human diet. Most contain phenolic compounds with high antioxidant activity, usually associated with human health protective functions. This attribute defines teas and infusions as nutraceutical foods. In Argentina, several native species are traditionally used for medical purposes. Some of those species are Larrea cuneifolia, Larrea nitida, Grindelia chiloensis, Pteromonnina dictyocarpa, Mandevilla laxa, and Monttea aphylla. The objectives of this study were to analyze the antioxidant power and the scavenging capacity of infusions obtained from those six medicinal plants, to characterize the phenolic profile, and to study in vitro their safety or cytotoxicity. Additionally, the potential use of two infusions as antioxidant additives in a food model was evaluated. The results indicated that the analyzed plant species are rich in phenolic acids (e.g., caffeic, ferulic, and chlorogenic acid), and flavonoids (e.g., quercetin and kaempferol), with high antioxidant power. The infusion blend obtained with G. chiloensis and L. cuneifolia exhibited the highest value of antioxidant capacity measured with the FRAP technique (193.4 μg EAA/mg DW). On the other hand, L. cuneifolia infusion showed the greatest antioxidant capacity determined by FRAP (131.9 ± 5.2 μg EAA/mg DW) and DPPH assays (0.453 mL/mg s). Additionally, L. cuneifolia infusion showed the highest phenolic content (232.8 μg GAE/mg DW) and flavonoid content (153.3 μg QE/mg DW). None of the infusions showed toxicity in mammalian cells, except for G. chiloensis. Furthermore, the L. cuneifolia and L. nitida infusions showed a high inhibitory effect on lipid oxidation in ground beef (55% and 51% at 4 days of storage, respectively). The results suggest that the studied infusions are safe and a rich source of antioxidants, which supports their use in traditional medicine. However, further exhaustive studies of G. chiloensis infusion are needed to ensure its safety, as it has shown cytotoxicity. Besides, it is worthwhile to advance the study of L. cuneifolia and L. nitida as sources of dietary antioxidants, due to their high antioxidant power and ability to protect against lipid peroxidation.

Graphical Abstract
Mechanical mitral valve endurance in children under 2 years
Authors: Mashali Mohamed H. , Elmahrouk Ahmed F. , Ahmad Zaheer , Abdulrahman Osama , Galleon Anas Farag , Al-Kouatli Amjad , Jamjoom Ahmed A. , Zahr Riad Abou
Published: July 2024

Background

The management of mitral valve disease in young children is challenging. Mechanical mitral valves could provide long-term durability; however, the need for anticoagulation increases the risk profile of mechanical valves. We report our experience in mechanical mitral valve replacement (MVR) in children under 2 years of age and evaluate factors affecting the outcomes.

The study included all patients younger than 2 years who underwent mechanical MVR between 2000 and 2023. The study outcomes were mitral valve reoperation, bleeding, valve-related thrombosis, and survival.

Results

Twenty-three patients were included, with a mean age of 10.2 ± 5.9 months. The mitral valve sizes ranged from 16 to 25 mm, and 6 (26%) were placed in the supra-annular position. Complete heart block occurred in seven patients (30%), and operative mortality occurred in three patients (13%). Postoperative warfarin was used in 17 patients (74%). After discharge, bleeding occurred in five patients (22%), four were managed conservatively, and one had intracranial hemorrhage treated with craniotomy. Nine patients (39%) had valve-related thrombosis; two underwent reoperation, while seven were treated with alteplase in 26 patients. Valve-related thrombosis was more common in patients with supra-annular valves (p < 0.001) and in those who were not on warfarin (p < 0.001). A total of seven patients (30%) underwent redo MVR, and redo was more common in young patients (p = 0.029) and in patients with supra-annular valves (p < 0.001). Survival of the whole cohort was 73% at 5 years. Among the annular position group, 5-year survival was 88%, while among the supra-annular position group, survival was 50% after 3 months and 25% after 14 months (p = 0.009).

Conclusions

Mechanical MVR in children younger than 2 years is associated with high complication rates, including thrombosis and bleeding. The supra-annular valve position appears to be a risk factor for thrombosis and reoperation. Anticoagulation with warfarin remains challenging. However, further studies evaluating alternative options are needed.

Graphical Abstract
Design of Y-shaped tri-band rectangular slot DGS patch antenna at sub-6 GHz frequency range for 5G communication
Authors: Singh Ajay , Joshi Sunil
Published: July 2024

This paper presents the design and development of a rectangular slot DGS patch antenna fed by a microstrip line, designed to operate across three distinct frequency bands at 4.0 GHz, 4.9 GHz, and 5.5 GHz for 5G wireless communication applications. The antenna design outlined in this study is implemented on a Fr-4 substrate with dimensions measuring 50.5 × 41.12 × 1.5 mm3. The antenna gains at three frequency bands are 2.69 dBi, 7.27 dBi, and 11.37 dBi having impedance bandwidths of 9%, 8.9%, and 5.1%, respectively. The attained bandwidths are 356 MHz, 443 MHz, and 287 MHz for the respective frequency bands. The radiation efficiencies of the proposed antenna are 90%, 82%, and 79% of the three respective frequencies. Antenna 1 in this study exhibits single-band behavior, effectively covering the single frequency band which is 5.5 GHz (5.3578–5.9519 GHz) 5G unlicensed band 5-GHz WLAN IEEE 802.11a frequency. On the other hand, Antenna 2 demonstrates dual-band characteristics spanning the S-band 3.7 GHz (3.5619–3.8544 GHz) and C-band range 5.1 GHz (4.8496–5.2008 GHz) suitable for mid-band 5G applications. Antenna 3 proposed antenna exhibits a tri-band functionality within the C-band spectrum. The results highlight multiple-band operation, consistent high gain, high directivity, and favorable directional radiation patterns.
Enabling uncertainty quantification in a standard full-waveform inversion method using normalizing flows
Authors: Sun Changxiao , Malcolm Alison , Kumar Rajiv , Mao Weijian
Published: July 2024

To maximize the utility of seismic imaging and inversion results, we need to compute not only a final image but also quantify the uncertainty in the image. Although the most thorough approach to quantify the uncertainty is to use a method such as Markov chain Monte Carlo, which systematically samples the entire posterior distribution, this is often inefficient, and not all applications require a full representation of the posterior. We use normalizing flows (NFs), a machine learning technique to perform uncertainty quantification (UQ) in full-waveform inversion (FWI), specifically for time-lapse data. As with any machine learning algorithm, the NF learns only the mapping from the part of the prior spanned by the training data to the distribution of final models spanned by the training data. Here, we make use of this property to perform UQ efficiently by learning a mapping from the prior to the distribution that characterizes the model perturbations within a specific range. Our approach involves using a range of starting models paired with final models from a standard FWI as training data. Although this does not capture the full posterior of the FWI problem, it enables us to quantify the uncertainties associated with updating from an initial to a final model. Because our target is to perform UQ for time-lapse imaging, we use a local wave-equation solver that allows us to solve the wave equation in a small subset of our entire model, thereby keeping computational costs low. Numerical examples demonstrate that incorporating the training step for NF provides a distribution of model perturbations, which is dependent on a designated prior, to quantify the uncertainty of FWI results.
Efficacy and safety of triplet nivolumab, relatlimab, and ipilimumab (NIVO + RELA + IPI) in advanced melanoma: Results from RELATIVITY-048.
Authors: Ascierto Paolo Antonio , Dummer Reinhard , Gaudy-Marqueste Caroline , Bowyer Samantha , Lipson Evan J. , Ghisoni Eleonora , Middleton Mark R. , Ratto Barbara , Jackson William Joseph , Cheong Alicia , Mukherjee Sourav , Wu Jenny , Long Georgina V.
Published: July 2024

9504

Background: NIVO (anti–PD-1 antibody) is approved as monotherapy and in combination with either RELA (anti–LAG-3 antibody) or IPI (anti–CTLA-4 antibody) for the treatment of patients (pts) with advanced melanoma. RELATIVITY-048 (NCT03459222) is a phase 1/2, nonrandomized trial evaluating immuno-oncology (I-O) triplets, including NIVO + RELA + IPI, for pts with select solid tumors. This analysis from RELATIVITY-048 focused on NIVO + RELA + IPI use in the advanced melanoma cohort and is the first disclosure from the study. Methods: Pts with advanced melanoma were treated with first-line NIVO 480 mg Q4W + RELA 160 mg Q4W + IPI 1 mg/kg Q8W until progression or unacceptable toxicity. Prior neoadjuvant/adjuvant therapy, including I-O agents, was permitted if completed > 6 mo before enrollment. Pts with controlled brain metastases were allowed to enroll. Primary endpoints were safety and confirmed objective response rate (ORR), disease control rate (DCR), and median duration of response (DOR) per investigator. The secondary endpoint was progression-free survival (PFS) per investigator (median and 6-mo/12-mo rates). Exploratory endpoints included overall survival (OS; median and 12-mo/24-mo rates). Results: In total, 46 pts were treated. Median follow-up was 49.4 mo (range, 0.4–55.0; database lock, Nov. 1, 2023). Median age was 61.0 y, 8.7% had cutaneous acral melanoma, 50.0% were BRAF positive, 73.9% were LAG-3 positive (≥ 1%), 26.1% were tumor cell PD-L1 positive (≥ 1%), and 6.5% had received prior adjuvant therapy. Median duration of treatment was 5.0 mo (range, 0.0–49.0). NIVO + RELA + IPI had a confirmed ORR of 58.7% and a 48-mo OS rate of 71.7% (table). Any-grade and grade 3/4 treatment-related adverse events (TRAEs) occurred in 44 pts (95.7%) and 18 pts (39.1%), respectively. Any-grade TRAEs led to treatment discontinuation in 19 pts (41.3%). Deaths due to TRAEs occurred in 2 pts (4.3%; rectal hemorrhage and dyspnea [n = 1], immune-mediated myositis [n = 1]). Conclusions: In RELATIVITY-048, NIVO + RELA + IPI demonstrated encouraging efficacy, with a confirmed ORR of 58.7% and a 48-mo OS rate of 69.1%. There were no new safety signals with NIVO + RELA + IPI, and the safety profile was generally consistent with I-O combinations. Given the small sample size, additional studies are needed to confirm the efficacy and safety of NIVO + RELA + IPI. Clinical trial information: NCT03459222 . [Table: see text]
Development of a novel granulocyte scoring system for use as a predictive/prognostic biomarker in patients with advanced melanoma undergoing treatment with combination immunotherapy.
Authors: Julve Max , Wong Yien Ning Sophia , Diez de los Rios Riobo Margarita , Garitaonaindia Yago , Rosero Diana I. , Needham Jazmine , Soto Juan Jose , Beland Chloe , Le Ha Mo Linh , Larkin James , Furness Andrew J.S.
Published: July 2024

9551

Background: Despite the implementation of immune checkpoint inhibition (ICI) for patients with metastatic melanoma, there remains an unmet clinical need for predictive/prognostic biomarkers to determine, from outset, which patients will derive benefit. Recent literature has suggested a significant role for granulocyte subsets in the development of resistance to systemic therapies, with an associated role in adaptive immunity. Methods: We sought to establish a novel immunological scoring system to use as a predictive/prognostic biomarker in patients with advanced melanoma being treated with ICI. In this retrospective, single centre study evaluating patients with advanced melanoma treated with combination ipilimumab and nivolumab, progression free survival (PFS) and overall survival (OS) were compared between groups defined by neutrophil, lymphocyte, eosinophil, monocyte and basophil counts. Data from 226 patients was collected at baseline, week 3, week 6, first response scan and at progression. Baseline and week 3 data was the focus of this primary analysis. Kaplan-Meier estimation and Cox regression analysis were performed. Results: Univariate analysis demonstrated that absolute neutrophil, eosinophil and basophil count strongly associates with PFS and OS outcomes at week 3. Combination of these counts into a novel neutrophil to eosinophil + basophil ratio (NEBR, (N/(E+B)) was assessed as a scoring system. High NEBR was associated with poorer PFS and OS at baseline and week 3 with consistently superior predictive/prognostic value than the well-established neutrophil to lymphocyte ratio (NLR). After accounting for covariates including concurrent steroids, infection and LDH, high NEBR remained significantly associated with worse PFS at baseline and poorer PFS and OS at week 3. Conclusions: Our findings highlight NEBR as a novel immunotherapeutic predictive/prognostic biomarker with potential clinical utility that warrants further investigation in patients with advanced melanoma and across other tumour groups. Further validation will be required through independent external datasets. [Table: see text]
Ultra-hypofractionated adjuvant radiation therapy for breast cancer (UK FAST-Forward trial): A real life scenario analysis in a developing country.
Authors: Aguiar Rennê Bart , Ferrari Ramon , Franco Leonardo Oliveira , Almeida Carlos Veloso , Canary Paulo , Przybysz Daniel
Published: July 2024

e12501

Background: Selected patients showed non-inferior outcomes after conservative surgery for early breast cancer in the FAST-Forward UK (26Gy in 5 fractions) when compared to standard to date treatment. This study triggered an important change in radiation therapy routines across the world. We aimed to establish a pattern of treatment related events at a third-world country cancer center. Methods: We retrospectively analyzed all patients treated with 26Gy in 5 fractions (1 week) from January 2020 to June 2023. All data was exported and analyzed for demographics. A clinical profile was traced, dosimetric parameters and side effects assessed based on individual inquiries to each patient, per and post treatment. A strict medical record was kept in order to understand patterns of side effects and results. Results: 101 individuals were identified. Mean age was 64 years, 48 (47%) patients experienced radiation dermatitis of any grade, 33 (32%) grade 1, 9 (8%) grade 2, 6 grade 3 or 4 (5%). Patients older than 60 years showed to be a significant factor for dermatitis development (34 over a total of 48 - 70%) and 8 (53%) over 15 had grade 2 or higher dermatitis. 27 (26%) developed radiation dermatitis during sessions. 21 (20%) took 7 or less days to heal; 27 (26%) had a recovery longer than one week at an average age of 65 years - being the majority of dermatitis grade 1. Reported toxicities were sharp pain 31 (30%), burning pain 24 (23%), edema 17 (16%) and pruritus 5 (4%). At the time of this study was completed, 3 reported deaths (2%) were reported - with a 97% rate of survival. Conclusions: The FAST-Forward trial regimen has 3 years since its publication. Our study shows that in a selected group of breast cancer patients, this novel model has shown to be a safe alternative for adjuvant radiation therapy following breast conservative surgery, results corroborating with published data. To the best of our knowledge, this is the largest single center group analyzed and published.
Risk factors of breast cancer among patients from a lower- and middle-income country: A case-control study from Nepal.
Authors: Shahi Arun
Published: July 2024

e12502

Background: Although breast cancer occurs overwhelmingly in high-income countries, there has been a recent increase in the incidence of breast cancer cases in low and middle-income countries. Reports from hospital-based registries showed that breast cancer is second most common cancer in Nepalese women. The study aimed to find the risk factors associated with breast cancer among breast cancer patients at a tertiary care hospital from Nepal. Methods: An Institutional-based 1:1 unmatched case-control study with a sample of 100 women was conducted at Patan Academy of Health Sciences, Patan Hospital, Kathmandu, Nepal, between May to October 2023. Women aged 20-84 years with histologically confirmed breast cancer within the last 4 years of the interview date were identified retrospectively as a study cases. Semi-structured questionnaire was used for data collection. Multivariate logistic regression model was used to calculate the adjusted odds ratio with 95%CI. Results: The significantly associated risk factors included age (41-50yrs: OR 5.03, >50 years: OR31.11), marital status (married: OR9.23), age at menarche (13-15 yrs: OR 3.79), and oral contraception use (OC user: OR 4.26). Conclusions: Emphasizing regular breast cancer screening programs above 40 years of age and adequate counselling and awareness about that risks and benefits of hormonal contraception among high-risk groups might help to mitigate the risk of breast cancer.
Efficacy and safety of concurrent capecitabine and radiotherapy as adjuvant treatment in triple negative breast cancer.
Authors: Trifanescu Oana Gabriela , Gales Laurentia Minea , Ciornei Ana , Serbanescu Luiza , Zamfir Denisa , Anghel Rodica Maricela
Published: July 2024

e12534

Background: Triple-negative breast cancer remains a very aggressive disease with few treatments option. Neoadjuvant dose dense chemotherapy, adjuvant therapy with capecitabine for residual disease and radiotherapy are standard treatments. The aims of this study were to evaluate the efficacy and safety of capecitabine concurrent with radiotherapy in initially clinical stage III patients with triple negative breast cancer in order to improve locoregional control and survival of these patients. Methods: We prospectively analyzed 24 patients with triple negative breast cancer with residual disease after dose dense neoadjuvant chemotherapy with Epirubicin and Cyclophosphamide and Docetaxel (in some cases with carboplatin) who received concurrent Capecitabine and radiotherapy in adjuvant setting. External beam radiotherapy to the hole breast was administered at a dose of 45–50.4 Gy in 25–28 fractions, concurrent with Capecitabine 825 mg/m2, 5 days/week. Results: Median age at diagnostic was 47.1±7.4. Stage distribution was as followed: 45.8% stage IIIA, 25% stage IIIB and 29.2% stage IIIC. Median follow-up was 31 months. Median Disease-Free Survival (DFS) was 48 months, with 76%, 68%, and 46% of patients without recurrence at 24, 36 and 48 months respectively. All patients presented with distant relapses. Median overall survival (OS) was not reached, and 3 years survival rate was 88%. Most common toxicities of concurrent radiotherapy and capecitabine were radiation dermatitis all grades in 100% of patients, grade 3 in 37.5% and grade 4 in 4.1%. Other side effects were neutropenia grade 4 in 8.3% and lymphopenia grade 4 in 45.8% of patients. Conclusions: Capecitabine concurrent with radiotherapy appears to be very efficacious and safe in the adjuvant treatment of breast cancer, especially in preventing local recurrence.
Retrospective study on the profile of patients undergoing intraoperative radiotherapy with INTRABEAM for breast cancer treatment at a Brazilian cancer center.
Authors: Pereira Ferraz Verônica , Neto Renato Cagnacci , Sanches Solange Moraes , Gondim Guilherme Rocha Melo , Makdissi Fabiana Baroni Alves
Published: July 2024

e12538

Background: Conservative breast therapy combined with adjuvant radiotherapy has been the preferred treatment for early-stage breast cancer for many decades. Considering that most breast cancer recurrences occur near the original tumor site, partial breast radiotherapy has become an alternative for patients in this scenario, allowing for a single-dose radiation application directly to the tumor site. This technique has advantages such as reducing local toxicity and improving the quality of life for treated patients, in addition to decreasing the waiting time for radiotherapy treatment in developing countries like ours. Our case series is the largest in Latin America to date, and we believe that reporting the results of our experience will be valuable for the scientific community and aid in treatment decision-making in low- and middle-income countries. Methods: This is a retrospective study based on data from the medical records of 209 patients with early-stage breast cancer undergoing conservative surgery and intraoperative radiotherapy at A.C. Camargo Cancer Center (São Paulo, Brazil) from 2016 to 2023. Results: In our cohort, 88.5% of tumors were invasive ductal carcinomas. The majority were T1b (41.8%), had histological grade 2 (45.4%), nuclear grade 2 (62.7%), and showed no axillary involvement (87.6%). All patients received intraoperative radiotherapy in a single dose of 20 Gy radiation at the tumor site with a voltage of 50 kV. In our study, 17.7% of patients required additional external radiotherapy due to postoperative histopathological findings inconsistent with treatment indication criteria, including 35.3% for micrometastasis and 32.4% for nodal macrometastasis, 10.8% for narrow or compromised margins, 10.8% for histological types not covered in the final report, 2.7% for multifocality, 2.7% for extensive ductal carcinoma in situ, 2.7% for negative progesterone receptor, and 2.7% for the presence of lymphatic vascular invasion. The average follow-up time for patients was 36 months. The local recurrence rate was 0.5%. Conclusions: The results of this study support established data indicating the efficacy of intraoperative radiotherapy in early-stage breast cancer treatment. Therefore, for carefully selected patients, this technique with should be considered as a treatment option. We will continue to follow this patient cohort to identify the occurrence of late recurrences and publish long-term follow-up data.
A nomogram to predict the risk of axillary upstaging in patients with Z0011-eligible breast cancer.
Authors: Li Xinyu , Liu Qiang , Li Yudong
Published: July 2024

e12606

Background: ACOSOG Z0011 trial showed that in early cT1-2N0 breast cancer patients with 1-2 positive lymph nodes in sentinel lymph node biopsy (SLNB) can safely omit axillary lymph node dissection (ALND) without compromising local control and long-term survival. Although it is widely accepted worldwide, controversy and concerns remain that the incidence of non-sentinel lymph node metastasis may lead to pathological lymph node (pN) upstaging and insufficient systemic treatment. This study aims to identify risk factors for having ≥4 metastatic lymph node (pN2-3) in patients who met Z0011 criteria and received SLNB. Methods: This is a retrospective study enrolled 733 cT1-2N0 breast cancer patients with 1-2 positive SLNs treated between 2011-2022 at Sun Yat-sen Memorial Hospital. All patients had received SLNB followed by ALND. Patients included were divided into the training and validation sets at a 7:3 ratio. Differences were compared between pN1(1-3 LN+) and pN2-3(≥4 LN+) in training set using either t test or chi-squared test. Multivariate logistic regression was conducted to identify risk factors for pN upstaging and to form the basis of a predictive nomogram. The validation was processed in the other validation set and nomogram performance was evaluated using the area under ROC curve (AUC). Results: Among the 733 patients enrolled, 127 (17.3%) patients had pN upstaging (pN2-3) after ALND. There was a big difference of pN upstaging between the patients with 1 (47/511, 9.2%) and 2 (80/222, 36%) positive SLNs. 488 patients were allocated to the training set, among which 18.2% had pN upstaging. In univariate analysis, pN were differed by cT stage, axillary ultrasound appearance, histological grade, molecular subtype, Ki67, lymph vascular invasion, pathological tumor size, SLN metastasis type (micrometastasis or macrometastasis), positive SLN numbers and negative SLN numbers. Multivariate logistic analysis resulted six independent risk factors associated to pN upstaging: ultrasound suspicious node (OR=1.93; 95% CI: 1.08-3.47), positive lympho-vascular invasion (OR=2.27; 95% CI: 1.25-4.13), larger tumor size (OR=2.07; 95% CI: 1.15-3.73), SLN macro-metastasis (OR= 9.15; 95% CI: 1.07-78.13), two positive SLNs (OR= 6.59; 95% CI:3.70-11.76) and less negative SLN number (OR=1.54; 95% CI: 1.22-1.89). These factors were used to construct a predictive nomogram, exhibiting excellent performance with AUC values of 0.819 and 0.827 in the training and validation cohorts respectively. Conclusions: The Z0011-eligible patients with two positive SLNs may have a high risk of pN upstaging and need to be cautious to spare ALND. A practical nomogram is helpful to identify patients at high risk of pN upstaging and avoid insufficient systemic treatment.
Real-world comparison: Neoadjuvant pembrolizumab (pembro-NACT) vs. dose-dense neoadjuvant chemotherapy (ddNACT) in early stage triple-negative breast cancer (TNBC).
Authors: Barbi Mali , Noel Jovanka , Lee Chung-Shien , Rahman Husneara , Cheng Kit
Published: July 2024

e12615

Background: The KEYNOTE-522 trial showed a significant improvement in pathological complete response (pCR) and event-free survival (EFS), leading to the FDA approval of pembrolizumab (pembro) combined with NACT for high-risk, early-stage TNBC. However, it utilized q3-week dosing for doxorubicin + cyclophosphamide (AC), not the ddAC regimen, which showed superior overall survival (OS) in the CALGB 9741 and EBCTCG trials. Consequently, the superiority of the KEYNOTE-522 regimen over ddAC remains uncertain. This retrospective case-control study compares TNBC patients treated with the KEYNOTE-522 regimen to controls treated with ddAC-NACT, reporting real-world efficacy and safety. Methods: Early-stage TNBC patients treated at our institute from Jan 2019 to Dec 2022 were included. Descriptive statistics outlined patient characteristics and clinicopathological data. Relative risk (RR) for pCR was calculated with a 95% confidence interval, and Kaplan-Meier estimated 1-year EFS and OS. Results: 97 patients were included, with 40 receiving pembro-NACT. Patient demographics and clinicopathological features didn't differ significantly, except for race (p = 0.047). Dose interruption was more common in the pembro group (p < 0.0001); nevertheless, most patients in both arms completed NACT and underwent surgery, mainly mastectomy. Immune-related adverse events reflected current reports. The pembro arm had a 1.43 times higher likelihood of pCR, but it didn't reach significance (RR=1.43, 95% CI: 0.89-2.28). Univariable associations between pCR and age, race, dose interruption, and dose of dexamethasone were not statistically significant; a multivariable model was not fitted for this reason. 1-year EFS and OS were not statistically different between the treatment arms (Table 1). Conclusions: In this real-world analysis, we observed a trend toward a higher rate of pCR in the KEYNOTE-522 compared to the ddAC regimen. Despite more dose interruptions with pembro, the 1-year EFS and OS were not significantly affected. While the more recent 5-year results from the KEYNOTE-522 trial have validated enhanced EFS, with OS data yet to mature, our findings didn't reveal clear short-term benefits. Larger studies are needed to assess long-term benefits, specifically in comparison to previously established standard therapies. [Table: see text]
Global perspective of barriers in research among oncologists from low-middle income countries.
Authors: Ordinario Mel Valerie Cruz , Trinconi Cunha Mateus Trinconi , Islam Muhammad Rafiqul , Mathai Sonia , Tolani Musliu Adetola , poojary shamali , Suleimenova Assem , Ben Abdallah Ichrak , Badgami Ranjana Karmacharya , Bardakhchyan Samvel , Chinchalker Gauri Gauraiya , Gössling Gustavo , Djordjevic Fedja Radmilo , Gueye Coumba , Ndumbalo Jerry , Patil Rucha , Shilpakar Ramila , Shrestha Anju , Tan Harold Nathan C.
Published: July 2024

e13781

Background: Cancer research in low-middle income countries (LMICs) face unique challenges, hindering advancements in patient care. Understanding the practices, barriers and strategic needs encountered by oncologists in LMICs is essential for enhancing research capacities and patient outcomes. This study aimed to assess the barriers and facilitators of research among oncologists in LMICs. Methods: This online cross-sectional survey engaged a diverse group of practicing oncologists from LMICs between December 8, 2023 and February 6, 2024. Respondents include both oncology trainees and consultants primarily from Asia (63%), Africa (18%) and Europe (10%). Using a validated questionnaire (test-retest reliability: 0.98), data analysis was performed using frequency and percentages to detail the survey responses, with 95% confidence intervals calculated to ensure the findings reliability. Results: A total of 276 participants from 29 countries, with a mean age of 38 years, responded to the survey. Fifty three percent (n=146) were male and 46% (n = 126) were female, four participants chose not to disclose. Majority of the respondents were trained in medical oncology and related specialties, 71% (n = 196). Forty one percent (n = 113) of them had less than 5 years’ experience as a cancer physician, while a significant proportion were mid-career oncologists with 5 to 15 years of experience. Regarding individual level barriers; 3% (n = 7) had 60 - 100% protected research time, 3% (n = 8) had local and international mentors, 36% (n = 100) had no biostatistical training, 50% (n = 138) had no clinical trial design training, 11% (n = 29) had utilized qualitative design, 60% (n = 165) had not participated in a population-based study, and 83% (n = 228) had not participated in translational research. In relation to system-level barriers; 30% (n = 84) had inadequate research infrastructure and 43% (n = 120) had no clinical trials unit. Respondents rated the degree of implementation of new research findings into local clinical practice as 3 on a five-point Likert scale. Conclusions: This study highlights the critical gaps in research capacity, resource availability, and infrastructure among oncologists from LMICs. Addressing these barriers through targeted interventions is imperative for advancing cancer research and improving patient outcomes in LMIC settings.
MRI-Linac radiation therapy outcomes in patients with prostate, breast and other advanced malignancies.
Authors: Kaur Lakhvir , Mcmillin Kim , Drokin Ashley , Srivastava Amar J. , Seung Steven K. , Solhjem Matthew C. , Bader Stephen Blake , Hansen Eric K. , Wang Chesebro Alice , Crittenden Marka R. , Young Kristina Hoot
Published: July 2024

e13811

Background: MR-guided radiation therapy offers an innovative approach, providing superior soft tissue contrast that enables clinicians to deliver higher doses to the target site with fewer fractions. The objective of the study is to assess objective response rates and adverse effects related to a community-based single-institution experience with the ViewRay MRIdian. Methods: An IRB-approved registrational trial was conducted at the Providence Cancer Institute starting May 2020, with data cutoff of September 2023. All patients treated underwent MR screening, and the target site(s) were treated using hypofractionated radiation therapy in ≤5 fractions. The primary endpoint was to assess adverse effects attributed to radiation therapy. Secondary measures included local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), overall survival (OS), and change in prostate-specific antigen (PSA) for patients treated definitively for prostate cancer. The assessments were performed under the guidance of experienced radiation oncologists. Results: From May 2020 to September 2023, n=257 patients received treatment on the MRIdian with a median follow-up of 430 days [range 4-1221 days]. One and 2-year LRFS was 92% and 87%, and excluding prostate and breast cancer, 83% and 70%. Definitive prostatestereotactic body radiation therapy(SBRT) was delivered to 117 patients and significantly reduced PSA (mean difference -6.27, p<0.0001), with no local failures to date. One and 2-year DMFS was 75% and 67%, though if excluding definitive prostate SBRT and partial breast irradiation, these were 48% and 33%. The OS rate at 1 and 2 years was 86% and 76%. Excluding prostate and breast cancer, the 1 and 2-year OS was 74% and 55%. Grade 3+ adverse events possibly or definitely attributable to radiation therapy were noted in 5% (n=13/257) of patients, including 2 possible treatment-associated deaths (bowel perforation following liver SBRT, and respiratory failure following lung SBRT and trastuzumab-deruxtecan systemic therapy). Conclusions: Our institutional experience with the MRIdian demonstrated high levels of local control, while overall survival was driven by out-of-field failures. Serious adverse events were infrequent, but more common in abdominal targets highlighting the need for careful planning and tight organs at risk (OAR) constraints, particularly if systemic therapy is delivered soon after radiation.
NXL-004: A novel trans-differentiation therapy for glioblastoma treatment.
Authors: Chen Yuchen , Chen Ming , Kuo Tsangchih , Zhou Kai , Jin Sen , Liu Meng , Chen Ming Moon , Chen Shiyuan , Li Xuetao , Jiang Zuoyu , Pu Liting , Chen Adalia , Gao Xiang , Xu Jie , Sheng Jian , Huang Yulun , Chen Gong
Published: July 2024

e14020

Background: Gliomas, tumors originating from glial cells in the brain and spinal cord, constitute 80% of all malignant primary tumors affecting the central nervous system, with glioblastomas (GBM) as the most prevalent and aggressive subtype accounting for approximately 60% of cases. Current treatment options for GBM, including surgery, radiation therapy, and chemotherapy, have limited effectiveness in improving patient outcomes. Therefore, there is a critical need for more effective therapeutic approaches to treat GBM. Methods: We present NXL-004, an adeno-associated virus (AAV) vector delivering the neural transcription factor NeuroD1 directly into GBM tumor cells, as a novel therapy for GBM. Various GBM models were utilized to investigate NXL-004 treatment for GBM, including U87 intracranial and subcutaneous models in mice, PDX model and GBM organoid. Results: The results demonstrated that NXL-004 significantly reduced tumor size compared to the control group; (D) NXL-004 exhibited a significant effect in prolonging the survival of the GBM mouse model. The median survival of mice treated with NXL-004 was 34 days post tumor implantation, whereas the control group had a median survival of only 16 days. Conclusions: Preclinical studies of NXL-004 have demonstrated that this intervention effectively reprograms tumor cells, downregulating glial cell- and tumor-related gene expression, while concurrently upregulating neuron-related gene expression. The induced differentiation towards non-dividing neurons results in significant inhibition of tumor cell proliferation, substantial reductions in tumor volume and prolonged survival in GBM-bearing mice. Additionally, NXL-004 has exhibited a favorable safety profile in toxicity studies in rats and non-human primates. These preclinical outcomes paved the way for subsequent clinical evaluation, representing a potential breakthrough in GBM treatment.
Socioeconomic disparities impact on the outcome of patients with diffuse and anaplastic astrocytoma: A SEER analysis of pediatric and adult populations.
Authors: Mostafa Neveen , Ahmed Mohamed Amin , Abd Elhameed Salwa Amin , Kafri Zyad
Published: July 2024

e14024

Background: Astrocytoma is a rare form of brain tumors that affects both pediatrics and adults. In this study we assessed the effect of socioeconomic disparities on the outcome of patients diagnosed with astrocytoma in the pediatric and adult settings. Methods: We queried the Surveillance, Epidemiology, and End Results (SEER) registry for patients diagnosed with diffuse and anaplastic astrocytoma between 2000 and 2020. Data were collected on age at diagnosis, tumor site, annual household income, urban/rural residence and time of death. The chi-squared test was used to assess the association between two categorical variables, the Mann-Whitney U test and the Kruskal-Wallis test were used for continuous data that were non-normally distributed. The Kaplan-Meier method was used for survival analysis. Statistically significant differences between the curves were estimated using the 2 tailed log-rank test. Results: Among 27,438 patients (males: 55.4%), 9.5% were under 18, 36.5% were 19-45, 23.7% were 45-60, and 30% were over 60. Ethnicity was 14.3% Hispanic, 6.7% Black, and 73.7% White. Common tumor sites were frontal lobe (30.4%), temporal lobe (20.4%), and parietal lobe (10.6%). 39% had income >$75K and 11.2% lived in rural areas. Median survival was the highest in patients under 18 (15.8 years), declining with age to 2.8 years for those over 60 (P<0.0001). Surgery improved outcomes across all ages. Pediatric patients who had surgery lived 2.7 years longer on average (12.8 vs 10.1 years, p<0.001), while adults who had surgery saw a 4.1 year gain (8.8 vs 4.7 years, p<0.001). Higherhousehold income (>$75k) improved survival across ages. The median OS for pediatric patients with higher income is 16.4 years compared to 15.5 years for patients with lower income with p= 0.02. For adult patients mean survival was 8.9 years for those who had higher income compared to 8 years for patients with lower income with p<0.001. Location didn't impact pediatric outcomes (15.8 vs 15.8 years), but adults in non-metropolitan areas had lower survival (6.9 vs 8.5 years, p<0.001). Conclusions: Age, surgery, household income and geographic location influenced the survival of patients with diffuse and anaplastic astrocytoma. Surgery was a key factor positively impacting both pediatric and adult populations. Household income similarly affects outcomes across age groups, with younger patients generally experiencing better outcomes.
Single center experience of IDH inhibitors in high-grade gliomas.
Authors: Garcia Catherine R. , Highsmith Kaitlin N. , Knight Stephanie , Puduvalli Vinay K. , Kamiya-Matsuoka Carlos
Published: July 2024

e14036

Background: IDH inhibitors have shown to improve progression free survival in low grade gliomas. Antitumor effect in high-grade gliomas is not well known, with conflicting views regarding the role of IDH mutations in high-grade gliomas and the potential for resistance to DNA-damage-inducing therapies. We present the outcomes of high-grade gliomas that were treated in our institution with IDH inhibitors. Methods: We performed a retrospective review of patients with gliomas treated with FDA approved IDH inhibitors (ivosidenib and enasidenib) in the past 5 years at our institution (January 1st 2019- January 1st 2024). Our search identified 32 patients of which 11 were identified as high-grade gliomas (both oligodendrogliomas and astrocytomas). Institutional Review Board PA17-0222 was used for this study. Results: Eleven high grade, IDH-mutant glioma patients treated with IDH inhibitors were identified with a median age at diagnosis of 31 years; 63.6% of these patients were men. Over 63% of patients were categorized as WHO grade 3 and 36.4% as grade 4 tumors. Over 63% of patients were astrocytoma (4 out of 7 patients with WHO grade 4 astrocytoma) while the rest were oligodendrogliomas. All patients underwent initial resection and had received radiation plus at least one prior line of systemic therapy prior to starting an IDH inhibitor. Over 72% were started on IDH-inhibitor therapy after 3 or more recurrences; previous lines of systemic therapy included temozolomide, bevacizumab, and lomustine. Five patients were treated with more than 1 cycle of IDH inhibitor, 2 patients with 8 cycles, and 1 patient with 18 cycles. Of the 11 treated patients, four had progression while on an IDH inhibitor, of which one patient died. IDH inhibitors were discontinued in two patients (due to headaches and abnormal liver enzymes). Median survival and progression free survival after IDH inhibitors were not reached. Conclusions: IDH inhibitors were started on patients with high-grade astrocytoma and oligodendroglioma after multiple recurrences and after receiving DNA-damage-inducing therapies. Prolonged responses were observed in 3 patients (one oligodendroglioma and two WHO grade 3 astrocytomas). Further investigation is needed to establish the role for IDH inhibitors in the treatment of high-grade gliomas.
Demographic and socioeconomic factors of enterochromaffin cell carcinoid.
Authors: Cheema Simardeep , Rizk Elizabeth , Joseph Angel , Moroz Mark , Grover Jasika , Reddy Abhigna , Gill Sukhmani Kaur , Nowlen Frances , Silberstein Peter T. , Lee Daniel , Demangone Michael , Rossi Anthony , Heise Craig , Hsia Beau
Published: July 2024

e16288

Background: Gastric carcinoid tumors, previously known as neuroendocrine neoplasms, are derived from enterochromaffin cells and show an increasing incidence globally. Neuroendocrine tumors often result in hormonal syndromes due to the production of exogenous hormonal peptides by the tumor. Current treatment options include surgical resection and somatostatin pharmacotherapy to blunt tumor growth. A gastric carcinoid malignancy that requires more investigation is enterochromaffin cell carcinoid (ECC). Considering the increasing incidence of gastric carcinoids, a retrospective investigation of demographic data involving enterochromaffin cell carcinoids was performed using the National Cancer Database (NCDB). Methods: The 2004-2019 NCDB was explored to perform a retrospective cohort analysis of patients diagnosed with ECC. 200 patients with a histologically confirmed diagnosis (ICD-O-3 code 8241/3) were identified. Descriptive statistics were used to analyze the following demographic data of patients in this study: race, sex, age, income quartile, facility type, Hispanic status, and Chales/Deyo score. Regression analysis was used to interpret incidence trends. Results: The NCDB identified 200 patients diagnosed with ECC from 2004-2019 with incidence rates varying over this time (R² = 0.0001). The mean age at diagnosis was 55 years (SD = 19.7, range = 14-90). Women (62%) were more likely to be diagnosed than men. The majority of patients were White (86%) and non-Hispanic (80%). Most patients (99.9%) received treatment for the remission of the cancer, predominantly through surgical means (86.5%). More patients were treated in an Comprehensive Community Cancer program (34.5%) than in an academic/research program (26.0%). The majority of individuals lived in metropolitan counties with a population greater than 1 million (54%) than in other metropolitan counties (22%). Most patients were in the fourth quartile of income earners (32.1%). The top primary site was the appendix (40.5%), and most individuals (79.5%) had Charles/Deyo comorbidity scores of 0. Conclusions: To the best of our understanding, this is the first NCDB investigation of Enterochromaffin Cell Carcinoid (ECC) and therefore addresses a meaningful educational disparity on the topic. Most ECC patients tend to be White, non-Hispanic individuals with a primary diagnosis site of the appendix, consistent with previous studies. Upon analyzing the socioeconomic factors of ECC patients, it was found that they often fall into the top income quartile, live in densely populated metropolitan counties, and receive treatment from a comprehensive community cancer program. Due to the significance of these demographic and socioeconomic factors, more research is needed to understand their impact on the diagnosis and treatment of ECC.
A single-center retrospective analysis of allergies and survival outcomes in pancreatic adenocarcinoma.
Authors: Li Peter Chi-Win , Saldia Amethyst , Olson Sara
Published: July 2024

e16299

Background: Survival from pancreatic adenocarcinoma (PDAC) remains poor, with a 5 year survival of 12.5%. A prior 2010 epidemiological study done at Memorial Sloan Kettering Cancer Center (MSKCC) found an association between self-reported allergies and improved survival in PDAC patients. In this retrospective study, we analyzed self-reported allergies and outcomes in both resected and unresected PDAC patients. Methods: Data including allergy status and clinical information were collected from an ongoing PDAC registry study at MSKCC. 1389 eligible PDAC patients were approached and 917 were enrolled between April 2004 and November 2017. 874 patients were included in our overall survival (OS) analysis using Kaplan-Meier methods. 43 patients were excluded due insufficient data or loss to follow up. Cox proportional hazards models were used to adjust for covariates. Results: Of the 874 patients analyzed, mean age at diagnosis was 63.5 years (standard deviation: 11.4), 52% were male, and race was 87% white, 6% black, 4% Asian, and 3% other race. 32.3% had surgery and 85% received chemotherapy. Median overall survival (OS) was 32.8 vs. 27.7 months [Hazard Ratio (HR) 0.95, p = 0.73] and 12.5 vs. 11.2 months [HR 1.04, p = 0.66] in for PDAC patients with allergies compared to those without in the resected and unresected cohorts, respectively. Advanced stage was associated with worse outcomes in both groups. Chemotherapy was significantly associated with improved survival only in the unresected group (HR 0.48, 95% CI 0.30-0.78, p = 0.030). Other established PDAC risk factors were also analyzed. Smoking history, diabetes, and family history were not associated with survival. Only obesity was significantly associated with worse outcomes in the unresected group (HR 1.3, 95% CI 1.01-1.67, p = 0.04). Conclusions: Contrary to previous findings, self-reported allergies were not significantly associated with improved survival in PDAC. In atopic patients, T helper type 2 cells are upregulated with allergen exposure and produce more IgE. Tumor-specific IgE has shown protective benefits in preclinical models but can be downregulated in the tumor microenvironment in PDAC. Further studies are needed to explore the relationship between allergies and PDAC and understand potential aspects of the immune system that can be harnessed to improve outcomes. One study limitation was that allergies were self-reported and not confirmed with allergy testing. We were also able to redemonstrate worse outcomes with more advanced stages and the benefit of chemo in the advanced setting. Further studies are needed to explore the mechanisms behind obesity and PDAC. [Table: see text]