bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.