bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of immediate vs. delayed guided tissue regeneration in Infrabony defect of second molars after adjacent third molar extraction: a retrospective study
Authors: Tang Si-Min , Liu Di-Xin , Xiong Zi-Yun , Shao Yi-Qian , Jiang Jing , Chen Li , Xiong Qin , Wu Shuo-Yan , Xuan Dong-Ying
Published: July 2024

Background

The distal aspect of the second molar (d-M2) often exhibits infrabony defects due to the adjacent third molar. Although the defects can be treated by guided tissue regeneration (GTR) after removing the third molar, the optimal timing remains uncertain following third molar removal in clinical decision-making. This study aimed to compare delayed and immediate GTR treatments to assist in clinical decision-making.

Methods

D-M2 infrabony defects with a minimum 1-year follow-up were collected and divided into three groups: Immediate GTR group, which underwent third molar extraction and received GTR simultaneously; Delayed GTR group, which underwent delayed GTR at least 3 months after third molar extraction; and Control group, which underwent only scaling and root planing during third molar extraction. The clinical and radiographic parameters related to the infrabony defect before GTR and post-surgery were evaluated using the Kruskal-Wallis test or one-way ANOVA, followed by post-hoc Dunn’s test or the Bonferroni test for pairwise comparisons.

Results

A total of 109 d-M2 infrabony defects were assessed. No significant differences were found between the two GTR groups, although both of them showed significant reductions in infrabony defect depth: the immediate GTR group (2.77 ± 1.97 mm vs. 0.68 ± 1.03 mm, p < 0.001) and the delayed GTR group (2.98 ± 1.08 mm vs. 0.68 ± 1.03 mm, p < 0.001) compared to the control group.

Conclusion

GTR can effectively improve d-M2 infrabony defects when the third molar is removed, whether simultaneously or delayed. Patients may experience less discomfort with immediate GTR treatment as it requires only one surgery.
Experiences and perceptions of palliative care patients receiving virtual reality therapy: a meta-synthesis of qualitative studies
Authors: Huang Yufei , Deng Cunqing , Peng Meifang , Hao Yanping
Published: July 2024

Background

The combination of virtual reality (VR) and palliative care potentially represents a new opportunity for palliative care. Many previous studies have evaluated the application of VR therapy to patients with advanced disease receiving palliative care. However, patient-perspective reviews to comprehensively understand the actual experiences and feelings of patients and provide practical guidance for designing future studies are currently lacking. This review of qualitative evidence aimed to explore the experiences and perceptions of patients receiving VR therapy in palliative care.

Methods

This study was conducted in accordance with the Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) statement guidelines. Ten databases, namely, PubMed, Web of Science, EBSCO, OVID MEDLINE, Scopus, John Wiley, ProQuest, CNKI, WANFANG DATA, and SinoMed, were searched, and qualitative and mixed studies from the establishment of each database to June 30, 2023 were included. The Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research was used to assess the quality of the included studies. The data included in the literature were analyzed and integrated by “thematic synthesis” to formalize the identification and development of themes.

Results

The nine selected studies altogether included 156 participants from seven hospice care facilities of different types and two oncology centers. Three key themes were identified: experiences of palliative care patients in VR therapy, the perceived value that palliative care patients gain in VR therapy, and perspectives of palliative care patients toward using VR therapy.

Conclusions

The patients’ feedback covered discomfort caused by VR devices, good sense of experiences, and situations that affected the interactive experience. Some patients were unable to tolerate VR therapy or reported newer forms of discomfort. The findings indicated that VR therapy may be an effective approach to relieve patients’ physical and psychological pain and help them gain self-awareness. Moreover, patients showed a preference for personalized VR therapy.
Utility of instant messaging application, WhatsApp, as a tool to augment post-graduate radiology education
Authors: Khan Sohail Ahmed , Shamim Shahid , Farooqui Waqas Ahmed , Sultan Rooha , Nisar Munizha , Adnan Noreen , Khan Ibrahim , Andani Hina
Published: July 2024

Background

Smart phone technology including different instant messaging applications like, WhatsApp, can be used for the development of radiological skills, reporting, and performance. To determine the utility, attitude, and outcome of WhatsApp for augmenting education in FCPS radiology residency program. To assess the opinion of radiology residents regarding WhatsApp as a tool to enhance postgraduate training.

Methodology

A mixed method (qualitative and quantitative) was conducted at Dow Institute of Radiology, Karachi, Pakistan. All FCPS Radiology residents were given a radiological case by principal investigator followed by residents’ response in 24 h. Key findings were shared by the mentor. Before and after the intervention of WhatsApp, all residents were evaluated with written and radiological imaging reporting exam. For quantitative analysis, a closed ended questionnaire was used containing information about total number of messages, images, webpage links shared, level of contribution (active/non-active), and utility (contribution in education related topic only). A feedback form with Likert scale was also got filled by all residents. For qualitative research, semi structured interviews (SSIs) were conducted.

Results

Median number of total images shared were 293 (IQR 1002 images), messages shared 110 (IQR), webpages shared were 54 webpages (61 webpages) and total contents shared by participants was 243 (544 contents). Active contributors showed better performance in utility, competency of contents and attitude towards using social media as a medium for learning. Comparison of written and OSCE results showed better performance after the intervention. Feedback form with Likert scale revealed that students responded positively regarding the shared learning content. Thematic analysis showed 52 codes and 16 themes.

Conclusion

In this research we have observed that WhatsApp is highly efficient and productive academic tool which can amplify postgraduate radiology education. Student’s narrative reflects that residents have found the missing link which can take them to radiological professional excellence through targeted high-profile learning outside lecture hall in time and place convenient motivational environment. Once it will be blended with existing teaching strategy, it can prove to be a game changer.
Predictors of grit among medical students: a study at a Malaysian Public University
Authors: Ibrahim Nurfauzani , Mohamad Mariam , Abdul-Razak Suraya , Mohamed-Yassin Mohamed-Syarif , Baharudin Noorhida
Published: July 2024

Background

Previous literature has demonstrated associations between grit and positive educational and psychological outcomes, such as higher academic grades, lower attrition rates in medical training, and protection from burnout. However, the predictors of grit have yet to be studied, particularly among medical students in Malaysia. This study aimed to determine the level of grit and its predictors among Malaysian medical students.

Methods

A cross-sectional study was conducted among 123 medical students from a public university in Malaysia. Data on sociodemographic and educational characteristics were collected. The student’s personality traits were determined using the Big Five Inventory (BFI), while grit was assessed using the validated 7-item Short Grit Scale (Grit-S). Grit was expressed as a mean score, ranging from 1 (not at all gritty) to 5 (extremely gritty). Multiple linear regression was used to determine the association between the predictors (personality, sociodemographic and educational characteristics) and grit among these students.

Results

The mean grit score was 3.43 (SD 0.57). Based on the multiple linear regression analysis, the grit score was significantly predicted by three personality traits which were extraversion, b = 0.2 (95% CI: 0.07–0.32), agreeableness, b = 0.28 (95% CI: 0.12–0.44) and conscientiousness, b = 0.6 (95% CI: 0.42–0.77). A 1-point increase in the mean extraversion, agreeableness, and conscientiousness scores would independently increase these students’ mean grit scores by 0.2, 0.28, and 0.6, respectively. The sociodemographic and educational characteristics did not significantly predict grit among Malaysian medical students.

Conclusions

The mean grit score among Malaysian medical students is comparable to other medical students in Asia. Extraversion, agreeableness, and conscientiousness personality traits were associated with higher grit. As grit is a dynamic trait, appropriate interventions should be implemented to foster and increase it among these students.
WHO antenatal care policy and prevention of malaria in pregnancy in sub-Saharan Africa
Authors: Olapeju Bolanle , Bride Michael , Gutman Julie R. , Wolf Katherine , Wabwire Scolastica , Atobrah Deborah , Babanawo Felicia , Akrofi Otubea Owusu , Atta-Obeng Christian , Soro Benjamin Katienefohoua , Touré Fady , Shekarau Emmanuel , Hendrickson Zoé M.
Published: July 2024

Background

The WHO 2016 antenatal care (ANC) policy recommends at least eight antenatal contacts during pregnancy. This study assessed ANC8 uptake following policy implementation and explored the relationship between ANC attendance and intermittent preventive treatment in pregnancy (IPTp) coverage in sub-Saharan Africa following the rollout of the World Health Organization (WHO) 2016 ANC policy, specifically, to assess differences in IPTp uptake between women attending eight versus four ANC contacts.

Methods

A secondary analysis of data from 20 sub-Saharan African countries with available Demographic Health and Malaria Indicator surveys from 2018 to 2023 was performed. The key variables were the number of ANC contacts and IPTp doses received during a participant's last completed pregnancy in the past two years. Pooled crude and multivariable logistic regression models were used to explore factors associated with attendance of at least four or eight ANC contacts as well as receipt of at least three doses of IPTp during pregnancy.

Results

Overall, only a small proportion of women (median = 3.9%) completed eight or more ANC contacts (ANC8 +). Factors significantly associated with increased odds of ANC8 + included early ANC attendance (AOR: 4.61: 95% CI 4.30—4.95), literacy (AOR: 1.20; 95% CI 1.11—1.29), and higher wealth quintile (AOR: 3.03; 95% CI 2.67—3.44). The pooled estimate across all countries showed a very slight increase in the odds of IPTp3 + among women with eight (AOR: 1.06; 95% CI 1.00—1.12) compared to those with four contacts. In all but two countries, having eight instead of four ANC contacts did not confer significantly greater odds of receiving three or more doses of IPTp (IPTp3 +), except in Ghana (AOR: 1.67; 95% CI 1.38—2.04) and Liberia (AOR: 1.43; 95% CI 1.18—1.72).

Conclusion

Eight years after the WHO ANC policy recommendation, all countries still had sub-optimal ANC8 + coverage rates. This paper is a call to action to actualize the vision of the WHO and the global malaria community of a malaria free world. Policies to improve ANC and IPTp coverage should be operationalized with clear actionable guidance and local ownership. Study findings can be used to inform multi-level policy, programmatic, and research recommendations to optimize ANC attendance and malaria in pregnancy prevention, thus improving maternal and child health outcomes, including the reduction of malaria in pregnancy.
An amplicon-based sequencing approach for Usutu virus characterization
Authors: Ndione Marie Henriette Dior , Diagne Moussa Moïse , Mencattelli Giulia , Diallo Amadou , Ndiaye El Hadji , Di Domenico Marco , Diallo Diawo , Kane Mouhamed , Curini Valentina , Top Ndeye Marieme , Marcacci Maurilia , Sankhe Safiétou , Ancora Massimo , Secondini Barbara , Di Lollo Valeria , Teodori Liana , Leone Alessandra , Puglia Ilaria , Gaye Alioune , Sall Amadou Alpha , Loucoubar Cheikh , Rosà Roberto , Diallo Mawlouth , Monaco Federica , Faye Ousmane , Cammà Cesare , Rizzoli Annapaola , Savini Giovanni , Faye Oumar
Published: July 2024

Usutu virus (USUV), an arbovirus from the Flaviviridae family, genus Flavivirus, has recently gained increasing attention because of its potential for emergence. After his discovery in South Africa, USUV spread to other African countries, then emerged in Europe where it was responsible for epizootics. The virus has recently been found in Asia. USUV infection in humans is considered to be most often asymptomatic or to cause mild clinical signs. However, a few cases of neurological complications such as encephalitis or meningo-encephalitis have been reported in both immunocompromised and immunocompetent patients. USUV natural life cycle involves Culex mosquitoes as its main vector, and multiple bird species as natural viral reservoirs or amplifying hosts, humans and horses can be incidental hosts. Phylogenetic studies carried out showed eight lineages, showing an increasing genetic diversity for USUV. This work describes the development and validation of a novel whole-genome amplicon-based sequencing approach to Usutu virus. This study was carried out on different strains from Senegal and Italy. The new approach showed good coverage using samples derived from several vertebrate hosts and may be valuable for Usutu virus genomic surveillance to better understand the dynamics of evolution and transmission of the virus.
Comparative efficacy of platelet-rich plasma (PRP) injection versus PRP combined with vitamin C injection for partial-thickness rotator cuff tears: a randomized controlled trial
Authors: Mohammadivahedi Fatemeh , Sadeghifar Amirreza , Farsinejad Alireza , Jambarsang Sara , Mirhosseini Hamid
Published: July 2024

Background

The optimal approach for managing partial-thickness rotator cuff tears (PTRCT) remains controversial. Recent studies related to PTRCTs have shown that platelet-rich plasma (PRP) injection might be an effective treatment option. Despite the role of vitamin C in collagen synthesis and its antioxidant properties, the effects of combined PRP and vitamin C treatment on rotator cuff repair are not well understood. This study investigated the effect of combined treatment of PRP and vitamin C treatment on PTRCTs.

Methods

One hundred-ten patients with PTRCTs were randomly allocated to two groups and underwent subacromial injections of either (A) normal saline and platelet-rich plasma or (B) vitamin C and platelet-rich plasma. The Constant score, American Shoulder and Elbow Surgeons (ASES) score, and visual analog scale were used to evaluate the outcomes before, 1 month after, and 3 months after injection.

Results

At the 3-month follow-up, no statistically significant differences were observed between the two groups in terms of ASES and Constant scores. Although a slight difference favoring group B was noted in functional scores and pain reduction, this difference was not statistically significant. However, both groups demonstrated significant pain reduction over time (p-value < 0.001). Additionally, the enhancement of ASES and Constant scores in both groups was statistically significant (p-value < 0.001).

Conclusions

In conclusion, both PRP injection alone and PRP combined with vitamin C led to significant reductions in pain and enhancements in function scores over time (p < 0.001), suggesting the effectiveness of PRP as a non-surgical treatment for PTRCTs within 3 months. While PRP alone showed significant benefits, further research is required to ascertain if the combination therapy offers statistically significant advantages over PRP alone.

Trial registration

Clinical trial registration code: IRCT20230821059205N1.
Validation of the Portuguese version of the diabetes self-management questionnaire-revised (DSMQ-R) in people with type 2 diabetes mellitus
Authors: Oliveira Dulce , Costa Andreia , Henriques Adriana , Curado Maria Alice , Schmitt Andreas , Nogueira Paulo
Published: July 2024

Background

Reflecting people with diabetes’ self-management activities is often required in both research and clinical practice. This study evaluated the measurement properties of the Portuguese version of the Diabetes Self-Management Questionnaire-Revised (DSMQ-R) on a sample of people with type 2 diabetes mellitus (T2DM).

Methods

Translation and cultural adaptation were conducted according to guidelines for cross-cultural adaptation and validation of healthcare measurement instruments. A cross-sectional study was performed including 365 people with T2DM in primary care. Reliability, construct validity, and criterion validity were analyzed.

Results

The total scale of the translated DSMQ-R revealed sufficient internal consistency (alpha = 0.82), and most of the subscales performed adequately. The exploratory factor structure was robust, and confirmatory analysis showed a good model fit with the scale structure of the original scale. The scale scores correlated with the participants’ last HbA1c estimates, supporting convergent validity, and convergence was confirmed by the adequate average variance extracted.

Conclusions

The Portuguese version of the DSMQ-R is a reliable and valid tool for gauging self-management behaviors in people with T2DM and their relationship with glycemic values.
Regression of cardiac angiosarcoma in a 17-year-old: a percutaneous biopsy effect
Authors: Sharrack Noor , Parent Martine , Lethaby Christopher , Rosendahl Ulrich , Lyon Alexander R , Farooq Maryum , Jamil Haqeel , Greenwood John P. , Plein Sven , Kidambi Ananth
Published: July 2024

Background

Cardiac angiosarcoma is a very rare and aggressive primary cardiac tumor associated with poor prognosis. Diagnosis is often delayed due to non-specific symptoms, with most cases involving metastases at the time of diagnosis. We describe a unique case of apparent tumor regression of cardiac angiosarcoma post percutaneous biopsy.

Case Presentation

A young male was admitted with suspected pericarditis. Echocardiogram revealed a pericardial mass. Cardiovascular magnetic resonance (CMR) suggested primary cardiac malignancy. Percutaneous biopsy was inconclusive, with subsequent CMR demonstrating apparent tumor regression. Interval imaging revealed further tumor growth, and surgical biopsy revealed primary cardiac angiosarcoma (PCAS). Causes of tumor regression following percutaneous biopsy are discussed.

Conclusions

Cases of suspected primary cardiac malignancy require careful follow up with serial multimodality imaging. Percutaneous biopsy effects should be considered in cases of tumor regression, and serial imaging should be planned afterwards.
Advancements in the application of nanotechnology for the management of epileptic seizures
Authors: Ping Honglu , Ding Ding , Zhu Guoxing , Wang Jianhong , Zhang Jun
Published: July 2024

Epilepsy is a common yet complex neurological disorder. Historically, antiseizure medications (ASMs) have faced challenges in crossing the blood-brain barrier (BBB) and targeting the epileptogenic zone, creating a bottleneck in seizure management. Certain nanomaterials can facilitate drug penetration through the BBB and enable stimulus-responsive drug release, thereby enhancing targeted and efficient drug utilization while reducing adverse reactions in other brain tissues and peripherally. This article reviews the current researches on stimulus-responsive nanosystems applicable in antiepileptic therapy, as well as nanotechnology applications that improve the brain delivery of ASMs.
Efficacy and safety of disitamab vedotin (RC48) in HER2-expressing breast cancer: A multicenter retrospective study.
Authors: Yang Can , Chang Jianying , Li Taolang , Liu Yuncong , Zhang Hanqun , Luo Xiaoqing , Xiang Yang , Zhang Cui , Huang Yisidan , Hou Jing , Wang Guanghui , Li Yong
Published: July 2024

e13011

Background: RC48 is an Antibody-Drug Conjugate (ADC) that integrates a humanized monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2) linked to the microtubule inhibitor monomethyl auristatin E (MMAE). This study reports real-world data using RC48 monotherapy in HER2-expressing advanced breast cancer (ABC). Methods: The study reviewed patients with HER2-expressing ABC who received RC48 monotherapy at three hospitals in China between September 2021 and June 2022. The electronic medical record was used to collect the clinical characteristics of the patient and to evaluate the antitumor activity and safety. The primary outcome was real-world progression-free survival (rwPFS). Results: A total of 15 patients were included, of whom 9(60%) were HER2-positive and 6(40%) had HER2 low expression (IHC 1+ or IHC 2+/ISH-).11 patients (73.3%) had visceral metastases, 40% of patients (6/15) had central nervous system (CNS) metastases at baseline. 6 patients (40%) had ≥3 metastatic lesions, and 13(86.7%) of patients received RC48 as third-line treatment or higher. Progression-free survival (PFS), overall survival (OS), and response can be assessed in all patients. The median follow-up was 10 months and the median rwPFS was 8.0 months (95% CI, 4.897-11.103), while the median OS was not reached. Objective response rate (ORR) and disease control rate (DCR) were 46.7% and 80% respectively. Partial response (PR) was achieved in 46.7% of the patients (7/15). patients with HER2-positive and HER2 low expression, the median rwPFS was 8.77 and 4.63 months, respectively (HR = 0.49,95% Cl, 0.13-1.80, P = 0.196), and in 6 patients with CNS metastases, the median rwPFS was 7.5 months (95% CI, 2.82-18.28). The most common treatment-related adverse events (TRAEs) were elevated transaminase (33.3%) and Leukopenia (33.3%), most of which were grade 1-2, No serious adverse events related to treatment were observed. Conclusions: The novel HER2-targeted ADC, RC48, demonstrated promising preliminary antitumor activity in patients with HER2-expressing ABC, patient with brain metastases could also benefit, with tolerable toxicities.
Real-world analysis of inetetamab combined with pyrotinib plus chemotherapy for the treatment of HER2-positive advanced breast cancer: A multi-center retrospective study.
Authors: Zhou Huanhuan , Chen Zhanhong , Deng Chao , Gan LU , Li Fan , Xu Xuefeng , Fang YanMan , Qi Xiaowei , Bian Wei Gang , Yu Zeshun , Wang Xiaojia
Published: July 2024

e13012

Background: Inetetamab combined with tyrosine kinase inhibitors exhibited stronger antitumor effects than inetetamab alone. At present, there was few studies on the efficacy and safety of inetetamab combined with pyrotinib in the treatment of advanced breast cancer (ABC) patients. The study aims to investigate the efficacy and safety of inetetamab combined with pyrotinib plus chemotherapy for HER2-positive ABC patients. Methods: We retrospectively investigated the medical records of eligible women who aged 18 years or older with pathologically confirmed HER2-positive recurrent or metastatic invasive breast cancer, and received at least two cycles of inetetamab combined with pyrotinib plus chemotherapy treatment regimens in multicenters in China between July 2020 and December 2022. The primary endpoint was progression-free survival (PFS) estimated by the Kaplan-Meier method. The secondary endpoints were the objective response rate (ORR), disease control rate (DCR), and safety. Cox regression model was used to identify predictive factors for PFS. Results: A total of 99 patients were included. Overall patient's median PFS was 12.3 (95% CI: 10.9-13.6) months. Of 99 evaluable patients, 53 (53.5%) patients achieved objective response, including 9 (9.1%) complete response and 44 (44.4%) partial response. The remaining 45 patients achieved stable disease as the best response, thus, the DCR was 99.0%. Patients who received Inetetamab combined with pyrotinib plus chemotherapy as first-line treatment (15.0 months [95% CI: 13.6-15.8]) provided longer median PFS than that as second-line treatment (10.3 months [95% CI:9.6-10.9], p<0.001). Furtherly, the Cox multivariate regression analysis indicated that patients who received inetetamab combined with pyrotinib plus albumin-bound paclitaxel for first-line treatment achieved longer median PFS. Grade 1-2 diarrhea (59.6%), vomiting (29.3%) and nausea (28.3%), hand-foot syndrome (23.2%) were the top four most common adverse events (AEs). The most common grade ≥3 AEs were leukopenia (19.2%), diarrhea (18.2%), myelosuppression (7.1%) and neutromenia (4.0%). Conclusions: The first-line treatment of inetetamab combined with pyrotinib plus chemotherapy was an effective and safe treatment for HER2-positive ABC patients. Inetetamab combined with pyrotinib plus albumin-bound paclitaxel might be the most effective combination therapies. All AEs were controllable and tolerable.
Efficacy and safety of inetetamab-containing regimens in patients with HER2-positive metastatic breast cancer in first-line/second-line setting.
Authors: Mu Yuxin , Meng Yanchun , Zhang Jian
Published: July 2024

e13013

Background: Inetetamab is a novel recombinant humanized anti-human epidermal growth factor receptor-2 (HER-2) monoclonal antibody. This real-world retrospective study assessed the efficacy and safety of inetetamab-based combination regimens in first-line/second-line treatment of HER2-positive metastatic breast cancer (MBC). Methods: This study retrospectively recruited HER2-positive MBC patients who received inetetamab-based combination regimens from June 2020 to May 2023. The outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Results: A total of 329 patients were enrolled and included in the efficacy analysis. The most frequently used treatment strategy was inetetamab plus pyrotinib-contained regimens (205/329, 62.3%). Patients treated with first-line regimens benefited the most, with a median PFS of 14.5 versus (vs.) 10.0 months (first-line- vs. second-line combination therapy of inetetamab, pyrotinib and chemotherapy, p <0.001), 18.0 vs. 17.0 months (first-line- vs. second-line combination therapy of inetetamab, pertuzumab and chemotherapy, p=0.096), and 14.0 vs. not applicable months (first-line- vs. second-line inetetamab plus chemotherapy, p=0.229). The complete response (CR) was observed in 14 (4.3%) patients. The ORR was 54.4% (95%CI, 49.0%-59.7%), and the DCR was 99.4% (95%CI, 97.8%-99.8%). Diarrhea (39.2%) and white blood cell count decreased (33.0%) were the most common adverse events (AEs). The grade 3 and higher AEs were observed in 29.5% of the whole study cohort. Conclusions: Inetetamab-based combinations therapy demonstrated promising clinical activity and a manageable safety profile in patients with HER2-positive MBC, especially in the first-line setting.
Can elective neck dissection for oral cancers be planned based on depth of invasion?
Authors: Majumdar Kinjal Shankar , Kottayasamy Seenivasagam Rajkumar , Malhotra Manu , Thaduri Abhinav , Panuganti Achyuth
Published: July 2024

e18042

Background: Elective neck dissection (END) is the standard of care for oral squamous cell carcinoma (OSCC). Literature suggests END may be avoided in primaries with depth of invasion (DOI) less than 4 mm. The present study evaluates the accuracy of DOI in predicting nodal metastases in OSCC. Methods: This retrospective study, approved by the Institutional Ethics Committee, includes all the patients with OSCC who underwent surgical excision. All tumors were classified and DOI was measured microscopically on resected specimens according to the AJCC TNM 8th ed. Statistical analysis was performed using IBM SPSS for Windows version 26. Pathological N-classification (pN) was correlated with DOI (in mm) using Spearman’s rank-order (pN1-3) and point-biserial (pN0 vs pN+) correlation statistics. Receiver operating characteristic (ROC) curve with area under the curve (AUC) were analyzed to determine the accuracy of DOI in predicting nodal metastases (pN+). Primaries were classified into three groups based on the range of DOI (≤5 mm; >5 mm and ≤10 mm; >10 mm) according to the AJCC TNM 8th ed. Chi-square statistic was used to measure the association between DOI groups and pN status (pN0; pN+). ANOVA with post hoc Bonferroni statistics were used to compare between three DOI groups. Results: Three hundred and thirty-seven (n=337) patients were screened for inclusion. After adjusting for missing data, 254 patients were included in the final analysis. Median age at presentation, DOI and nodal yield were 46 (24-82) years, 11 (1-40) mm, and 35 (1-121), respectively. Depth of invasion failed to demonstrate a strong positive correlation with pN classification (ρ=0.31; p<0.001). DOI did not show a strong correlation with pN status (pN0 vs pN+) either (rpb=0.27; p<0.001). ROC curve analysis suggested a poor accuracy of DOI in predicting nodal metastases (AUC=0.67; 95% CI 0.6-0.73). There was a statistically significant association between DOI groups and pN status (Chi-square=26.67; p<0.001). ANOVA with post hoc Bonferroni showed statistical significance only for DOI >10 mm group (p<0.001 for DOI ≤5 mm; p=0.02 for DOI >5 mm and ≤10 mm). However, the sensitivity and specificity achieved by the ROC analysis for DOI cut-off value of 10mm in the present cohort were merely 69.3% and 57.9%, respectively. Conclusions: DOI alone is a poor predictor of nodal metastases in OSCC. Though all correlations in the present study achieved statistical significance, none demonstrated a strong association or an accuracy credible enough of clinical importance. END should remain the standard-of-care for all OSCC, including early primaries with DOI <4 mm.
Association between heavy metal concentrations and chemotherapy-related acute adverse events in the patients with nasopharyngeal carcinoma: A prospective, longitudinal, observational study.
Authors: Chen Xi , Gao Tian-Rui , Qian Chao-Nan , Lv Xing , Guo Xiang , Peng Li-Xia
Published: July 2024

e18045

Background: Chronic exposure to heavy metals may cause chronic burden on liver, kidney, bone marrow and other organs. To determine whether the accumulation of heavy metals prior to treatment was related to the occurrence of acute adverse events in patients with nasopharyngeal carcinoma (NPC) receiving platinum-based chemotherapy, we conducted a single-center, prospective, longitudinal study. Methods: The heavy metal concentrations of pretreatment whole blood samples and the pretreatment and posttreatment morning urine samples for 140 NPC patients were measured, which were classified into low and high levels based on the 75% quartile. The highest grades of acute adverse events for every cycle of platinum-based chemotherapy were recorded according to the Common Terminology Criteria for Adverse Events (version 4.03). Wilcoxon rank-sum test was used to compare the difference in the distribution of acute adverse events between two levels. To illustrate the potential relationship of metal between in blood and urine, the spearman’s correlation coefficient of metal concentration in blood and urine adjusted by creatinine was calculated. The kendal's correlation coefficients were calculated to characterize the correlation between heavy metal levels and acute adverse events. Finally, the study developed multivariable adjusted logistic regression models to calculate odds ratios (OR) and 95% CIs of the association between various heavy metals and risk of chemotherapy-related acute adverse events, respectively. Results: The study enrolled 140 patients with stage II (n=2, 1.4%), III (n=76, 54.3%), and IVa (n=62, 44.3%) NPC. A total of 13 heavy metals of both blood and urine samples were measured, with Cd, Pb, Hg, As, Pt, Mg, Ca, Cr, Co, Ni, Cu, Zn, and Se included. The concentrations of the same metals in blood and urine (including Cd, Pb, Hg, As, Pt, Co and Se) had a moderate correlation (0.2 < correlation coefficient < 0.7). High level patients were prone to experiencing acute adverse events ( p<0.05). In multivariable adjusted logistic regression, patients with impaired liver function had higher BCd (Cd in blood) level (OR, 3.65; 95% CI, 1.38–9.64; p=0.009). Patients with thrombocytopenia had higher UCr (Cr in urine) level (OR, 5.63; 95% CI, 1.60–19.87; p=0.007). And UPb (OR, 3.16; 95% CI, 1.26–7.92; p=0. 014) and UZn (OR, 2.69; 95% CI, 1.10–6.59; p=0. 030) were found significantly higher in patients with abnormal blood glucose. Conclusions: NPC patients with chronic accumulation of BCd had tendency to have impaired liver function when receiving platinum-based chemotherapy. Similar correlations were also observed in the thrombocytopenia with UCr, and the abnormal blood glucose with UPb and UZn.
Neoadjuvant docetaxel-cisplatin followed by concurrent chemoradiotherapy and adjuvant tislelizumab for locally advanced nasopharyngeal carcinoma: A multicenter, single-arm, phase II trial.
Authors: Yuan Yawei , Tian Yunhong , Zhong Huang , Zheng Ronghui , Jie Lin , Zhang Jian , Liao Kai , Deng Jin , Yu Yi , Qiu Wenze , Bu Junguo , Zheng Rong , Xu Benhua , Chen Yong
Published: July 2024

e18047

Background: Patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) have a high risk of distant metastasis or recurrence despite the current standard of neoadjuvant chemotherapy and concurrent chemoradiation (CCRT), indicating the need of more comprehensive treatment. Due to good compliance and convenient adverse event management, the TP (docetaxel and cisplatin) regimen is more widely accepted and commonly used as a neoadjuvant chemotherapy for LA-NPC in the real world. Immune checkpoint blockade therapy plus chemotherapy has been shown to improve the survival in recurrent or metastatic NPC. We investigated the efficacy and safety of tislelizumab, an anti-PD-1 monoclonal antibody, as adjuvant treatment in patients with LA-NPC that had the neoadjuvant TP chemotherapy and CCRT. Methods: This multicenter, open label, single arm, phase II clinical trial was done at four hospitals in China. Patients (aged 18-65 years) with histologically confirmed, LA-NPC (T4N1 and T1-4N2-3) were enrolled and treated with neoadjuvant chemotherapy for 3 cycles (docetaxel 75 mg/m2 D1, cisplatin 75 mg/m2 D1) followed by concurrent cisplatin (100mg/m2, D1 and D22) during intensity-modulated radiation (IMRT). Four weeks post-RT, tislelizumab (200 mg) was given intravenously once every 3 weeks for up to 12 cycles. By Fleming one-stage design (type I error 0.05, power 0.80, 10% drop out), planned sample size is 100. Primary endpoint is 3-year (yr) progression free survival (PFS). Secondary endpoints include safety and tolerability. Results: From June 2021 to January 2024, a total of 100 patients (median age 53y, 73.0% male) were recruited at four study sites. This protocol specified analysis included 78 subjects with >12 months post-treatment follow up (median 26.2 months, 95% CI 21.3-30.1). Overall compliance rate: neoadjuvant cisplatin + docetaxel 97.5%, concurrent cisplatin 80.8%, adjuvant tislelizumab 78.2%, IMRT 99.7% (69.96 Gy). Treatment related adverse events (AEs, ≥grade 3, >10%): dysphagia (30.5%), mucositis (26.2%), neutropenia(26.7%), radiation dermatitis (23.7%), anemia (16.2%). No ≥grade 4 mucositis/dermatitis. In addition, the incidence of immune-related adverse events (irAEs) of grade 3 or 4 was 5.2%, and all were thyroid toxicity and skin rash. The 2-yr PFS and 2-yr overall survival were 89.6% (95% CI 53.8 - 88.5%) and 100%, respectively. 3-yr PFS and long-term efficacy are awaited. Conclusions: Tislelizumab adjuvant therapy after neoadjuvant docetaxel -cisplatin followed by CCRT is safe with promising results for LA-NPC. However, further follow-up is needed to confirm the long-term efficacy. Clinical trial information: NCT04870905 .
Is the gemcitabin cisplatin doublet the optimal induction chemotherapy for non-Asian patients with NPC? Insights from a northeastern Moroccan cohort.
Authors: Talbi Oumaima , Mhirech Samia , Hinaje Khadija , Maadin Kaoutar , Elhilali Hafssa , Chakri Imad , Bouhafa Touria , Amaadour Lamiae , Oualla Karima , Benbrahim Zineb , Nawfel Mellas , Arifi Samia
Published: July 2024

e18057

Background: According to the latest guidelines for NPC, induction chemotherapy followed by concomitant chemoradiation therapy (CCRT) is recommended as the preferred standard of care for patients with locally advanced nasopharyngeal carcinoma (stage III-Iva). However, the optimal regimen for induction chemotherapy (IC) in patients with locally advanced NPC remains uncertain. Methods: We conducted a retrospective study between January 2016 and October 2022 at the "CHU Hassan II" Oncology Hospital in Fes, Morocco, to compare the efficacy and tolerability of two platinum-based induction therapy regimens: cisplatin gemcitabine (GC) and cisplatin doxorubicin (DP), in the treatment of newly diagnosed locally advanced NPC. The main objectives of this study were to compare the efficacy including objective response rates (ORR), PFS ,OS and safety. Results: After eligibility assessment, we included 105 cases (62 patients in the DP group and 43 in the GC group), including 65 men and 40 women, with a mean age of 49.5 years (range = 19-79years) and a Karnofsky score ranging from 87% to 100%. 34% of patients were diagnosed at stage IVA. In the DP group, 3% of patients (2 out of 62) achieved a complete response CR, 60% achieved a partial response PR,25% remained stable SD and 19% experienced progression. In the GC group, 2% of patients (1 out of 43) achieved a CR, 39.5% achieved a PR, 39.5% remained stable, and 19% experienced progression. A statistically significant difference in PR was observed between the two groups (p = 0.028) ,and the difference in terms of progression is approaching the limit of significance (p=0,06) after a median follow-up of 27 months (5,3 -82). The 2-year progression-free survival (PFS) was 70% in the DP group compared to 80% in the GC group; the 2-year overall survival (OS) was 75% in the DP group and 90% in the GC group. No significant survival difference was observed between the two groups Patients in the DP group exhibited less grade 3-4 thrombocytopenia but more grade 3-4 leukopenia and neutropenia compared to the GC group. Conclusions: In patients with locally advanced nasopharyngeal carcinoma, GC-based induction chemotherapy demonstrated superior ORR over the DP regimen with acceptable toxicities. Further studies are needed to validate these results.
Impact of joint peer review with a specialist radiologist in head and neck cancer radiotherapy planning.
Authors: Mahajan Abhishek , Brammer Caroline , Haridass Anoop , Brooker Rachel , Ibrahim Ehab , Soni Manjusha , Zulfiqar Ali , Romaniuk Christopher
Published: July 2024

e18059

Background: Head and neck oncology is heavily dependent on interpretation of radiology. This raises the question whether input from radiology should be formally scheduled as part of the radiotherapy contouring processes. Our aim was to assess the impact of this practice through qualitative and quantitative analysis. Methods: H & N patients treated with radiotherapy between May-2022 and August-2023 were reviewed by a specialist HN radiologist. Incidence of changes in T, N, M and TNM-stage, change as defined by The RCR guidance: 'major' (change in gross tumour volume and/or high-dose clinical target volume, dose/fractionation) or 'minor' (change in intermediate or elective dose clinical target volumes or organs at risk), was recorded. We evaluated whether any of these changes were time dependent (Time interval between MDT to RT Peer Review). Other clinical variables: age, gender, primary diagnosis, tumour site, significant incidental findings, post-operative pTNM, post-operative disease status in adjuvant setting on planning imaging (NIRADS), need for additional imaging. We also recorded number of scans reviewed per patient, types of imaging studies reviewed, time taken for review and number of radiologist PA’s required. Retrospective analysis of a prospective database was performed. Results: 410 patients (252-definitive, 137-adjuvant, 21-palliative) were reviewed of which 51.5%-oropharynx followed by 26.8%-Larynx & Hypopharynx. Mean age was 66.14 yrs (SD 11.46) and M:F was 4:1. Baseline and Therapy planning imaging was reviewed for 100% patients of which baseline included: MR (91.7%), CT (96.1%), US (34.1%), PETCT (31%) and therapy planning (62%-CECT, 19%-MR&CT, 15%-CT, 4%-PETCT). In all patients (n=410), T/N/M/TNM-stage percentage upstage was 27/36.8/8.3/42.2% and in definitive cohort (n=252), it was 41.7/56.7/7.1/59.5%. Reviewing RT-planning Imaging in adjuvant cohort (n=137), 76.6% were NIRADS-1, 11.7% NIRADS-3/4/loco-regional disease and 11.7% distant metastasis. T/N/M/TNM-stage upstage was time dependent and the mean time interval between MDT to RT was higher in upstaged patients (p <0.001). Overall percentage change in treatment plan: no/minor/major/palliative was 40.5/33.9/17.3/8.3% and in definitive cohort 30.2/42.1/20.6/7.1%. Change in plan was not dependent on mean time interval between MDT to RT. Average 10 patients (4 imaging studies/patient) were reviewed by radiologist in 1PA (time to review and peer review meeting time). Conclusions: Routine head and neck radiologist input in radiotherapy peer review is feasible and resulted in a number of major and minor changes to treatment. Inputs not only eased the contouring for oncologists but also lead to updating of current disease stage just prior to treatment. Overall, our results suggest that this is a practice changing step in the radiotherapy workflow which has a direct impact on patient management.
Implementing fragmentomics into real world screening interventions to evaluate clinical utility among individuals with elevated risk for lung cancer (FIRSTLUNG) L301.
Authors: Cotton Lindsey Behlen , Cisar Chris , Bach Peter Brian , Sheridan Carolina , Trivedi Niti U. , Davis James , Tennefoss Demetria
Published: July 2024

TPS11189

Background: To optimize the impact of lung cancer screening at the healthcare system level, additional tools are needed to increase the benefits of screening. While low-dose computed tomography (LDCT) has been shown to improve lung cancer detection and reduce mortality, it is not without its risks, such as radiation exposure, false-positive results, and unnecessary interventions often leading to complications. The additional complexity of lung cancer screening is the subpar adherence to LDCT for eligible individuals, which undermines the benefits of screening. Therefore, there is a need for alternative non-invasive methodologies that exploit our understanding of the biology of cancer pathogenesis. This clinical utility study aims to observe how a non–invasive blood-based test impacts physician behavior and LDCT utilization. Methods: FIRSTLUNG 301 (NCT06145750) is a prospective, cluster randomized controlled trial (RCT) to observe the impact of the DELFI Lung cancer screening test on lung cancer screening utilization in primary care practices. Enrolled practices must meet the eligibility criteria of having a minimum of 50 actively engaged individuals in the practice eligible for lung cancer screening per the 2021 USPSTF criteria. These practices will be randomized 1:1:2 to Arm A1 (control), Arm A2 (control), or Arm B (intervention). Arm A practices will be randomized 1:1 into two groups (A1:A2) to observe the standard of care for lung cancer screening. Practices in A1 will be observed; practices in A2 will receive standard education on lung cancer screening for CME credit. Randomizing within Arms A1 and A2 aims to delineate the impact standard lung cancer screening education may have on utilization. Arm B (intervention) practices will receive education and have access to order the blood-based test for screen-eligible individuals that remained unscreened. The primary study endpoint is the proportion of practice-identified lung cancer screen-eligible individuals receiving a screening CT order and scan during the study period in the entirety of Arm A (control) versus Arm B (intervention). This RCT aims to understand the utilization and impact on lung cancer screening uptake after the DELFI blood-based test intended to inform clinical guidelines and policies focused on improving patient care and health outcomes. Progress: The study was initiated on October 31, 2023, with practice randomization. As of February 2024, the study is open for enrollment with an estimated primary study completion date of December 2025. Clinical trial information: NCT06145750 .
Triage of advanced cervical cancer through immunotherapy induction (TRACTION).
Authors: How Jeffrey Andrew , Rauh-Hain Jose Alejandro , Grinsfelder Michaela , Rangel Kelly M. , Roder Sarah , Shafer Aaron , Schmeler Kathleen M. , Boruta David M. , Fleming Nicole D. , Lu Karen H. , Vining David J. , Frumovitz Michael M. , Jazaeri Amir A.
Published: July 2024

TPS5622

Background: In advanced/recurrent cervical cancer, immune checkpoint inhibitors have emerged as an attractive alternative and have demonstrated impressive therapeutic responses. As a result, the combination of pembrolizumab with platinum/taxane chemotherapy with or without bevacizumab received FDA approval for first-line systemic therapy in persistent, recurrent, or metastatic PD-L1+ cervical cancer. However, this regimen demonstrates the greatest impact on survival when all four drugs are utilized and are not without the potential for significant toxicity. CheckMate-358 utilized two dosing regimens of ipilimumab and nivolumab in advanced/recurrent cervical cancer. In the preliminary results, the utilization of either dosing regimen resulted in remarkable, durable responses in chemo-naïve patients with the median overall survival not reached. Given the potential benefit of CTLA-4/PD-1 blockade in the upfront setting, we propose a phase II trial examining the strategy of induction immunotherapy with lorigerlimab (bispecific antibody targeting CTLA-4 and PD-1) in chemo-naïve cervical cancer patients not amenable to curative treatment. Methods: The study is a phase II, multi-site clinical trial conducted at MD Anderson Cancer Center and Lyndon B. Johnson General Hospital. In the induction phase, patients will receive intravenous (IV) lorigerlimab at the recommended phase II dose (6 mg/kg) for three 21-day cycles with a repeat CT scan performed at week 9 of treatment. Tumor response (by RECIST v1.1) to induction immunotherapy will be used to triage patients to either continuation of lorigerlimab (if at least stable disease) or standard of care treatment (if disease progression) in the triaged treatment phase. Lorigerlimab will be continued until progression or intolerable toxicity, for a maximum of 35 cycles. At any time point, all patients at first disease progression will subsequently receive physician’s choice standard of care systemic therapy with carboplatin/paclitaxel +/- pembrolizumab +/- bevacizumab and will be followed for survival. The primary objective is to estimate disease control rate. Secondary objectives are to determine objective response rate, duration of response, overall survival, progression-free survival, and safety (by CTCAE v5.0). Key eligibility criteria include 1) recurrent, metastatic, or persistent cervical cancer 2) squamous cell carcinoma, adenosquamous, or adenocarcinoma histologic subtype 3) not amenable to curative surgery or radiation. The trial is open with 14 of planned 40 patients enrolled at the time of submission. Clinical trial information: NCT05475171 .