tbuckley/cabot-search huggingface dataset:
Association between heavy metal concentrations and chemotherapy-related acute adverse events in the patients with nasopharyngeal carcinoma: A prospective, longitudinal, observational study.
Authors: Xi Chen, Tian-Rui Gao, Chao-Nan Qian, Xing Lv, Xiang Guo, Li-Xia Peng
Journal: Journal of Clinical Oncology (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 &lt; correlation coefficient &lt; 0.7). High level patients were prone to experiencing acute adverse events ( p&lt;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.
Increased adrenal steroidogenesis and suppressed corticosteroid responsiveness in critical COVID-19
Authors: Tian-Zi Wen, Tian-Ran Li, Xin-Yu Chen, He-Yuan Chen, Shuai Wang, Wen-Juan Fu, Shi-Qi Xiao, Jie Luo, Rui Tang, Jia-Le Ji, Jia-Feng Huang, Zhi-Cheng He, Tao Luo, Hong-Liang Zhao, Cong Chen, Jing-Ya Miao, Qin Niu, Yan Wang, Xiu-Wu Bian, Xiao-Hong Yao
Journal: Metabolism (2024)
Multi-dimensional cell-free DNA-based liquid biopsy for sensitive detection of head and neck squamous cell carcinomas.
Authors: Han Fang, Yakui Mou, Wenbin Zhang, Hua Bao, Min Wu, Xiaoxi Chen, Xuxiaochen Wu, Ruowei Yang, Dongqin Zhu, Xicheng Song
Journal: Journal of Clinical Oncology (2024)

e18054 Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type worldwide. The mortality from HNSCC is closely linked to stage. However, the majority of HNSCC patients were diagnosed at an advanced stage. Therefore, a non-invasive assay for the early detection of HNSCCs is highly desirable for reducing the associated mortality. Methods: We collected a study cohort of 281 participants including 140 pathologically confirmed with head and neck squamous cell carcinomas (HNSCCs) and 141 with non-cancerous conditions. A plasma sample was collected from each participant along with general health screening examinations before any invasive examinations. We performed low-pass whole-genome sequencing with plasma samples and profiled three types of cell-free DNA (cfDNA) characteristics, fragment size pattern (FSP), copy number variation (CNV), and single nucleotide substitution (SNS). We developed an ensemble model with these differential profiles to identify HNSCC patients from non-cancer individuals. We further collected a validation cohort consisting of 90 HNSCC patients and 95 non-cancer individuals to validate the cfDNA-based assay. Results: The liquid biopsy assay that incorporated three types of cfDNA characteristics was able to identify HNSCC patients from non-cancer individuals at an AUROC of 0.989 in the study cohort and 0.984 in the validation cohort. At a specificity of 95.7% (135/141), it achieved a sensitivity of 95.7% (134/140) in the study cohort. With this threshold (0.580), in the validation cohort, 93.7% (89/95) of non-cancer individuals and 93.3% (84/90) of HNSCC patients were correctly identified. Specifically, the sensitivities in early stage (I&amp;II) HNSCCs were 94.5 % (52/55) and 87.5% (28/32) in the study and validation cohort, respectively. Of note, the inferred probabilities of cancer showed consistent trends to increase with pathological stages in both cohorts (P=0.032 and 0.047, respectively). On the contrary, the differentiation grades and sub-locations did not significantly affect the performance of the assay. Conclusions: We introduced a liquid biopsy assay using multiple dimensions of cfDNA characteristics that could accurately identify HNSCCs from non-cancerous conditions. As a cost-effective non-invasive approach, it may be conveniently incorporated into annual general physical examinations to provide supplementary information about the risk of HNSCCs.
Association of low adherence to weekly cisplatin with outcomes in patients with head and neck cancer treated with chemoradiation.
Authors: Jas Virk, Jasmin Gill, Fatemeh Fekrmandi, Austin Iovoli, Mark Farrugia, Sung Jun Ma, Anurag K. Singh
Journal: Journal of Clinical Oncology (2024)

e18053 Background: The National Comprehensive Cancer Network (NCCN) guideline recommends consideration of weekly cisplatin as an alternative option for patients with head and neck cancer undergoing definitive chemoradiation. However, in a recent phase III trial (ConCERT), 20% of patients treated with weekly cisplatin could not receive a total of 200 mg/m 2 , and the association of low adherence to weekly cisplatin and cancer control outcomes remains unclear. To fill this knowledge gap, we performed an observational cohort study of patients with head and neck cancer undergoing definitive chemoradiation with weekly cisplatin. Methods: Our institutional database at the Roswell Park Comprehensive Cancer Center was queried for patients with non-metastatic head and neck cancer who underwent definitive chemoradiation with weekly cisplatin (40 mg/m 2 ) between November 2007 and April 2023. Adherence to weekly cisplatin was defined as receiving at least 5 cycles with a total cumulative dose of 200 mg/m 2 . Survival outcomes were evaluated using Kaplan-Meier method, log-rank tests, Cox proportional hazard multivariable (MVA) analyses. Logistic MVA was performed to identify variables associated with low adherence to weekly cisplatin. Fine-Gray MVA was performed to analyze failure outcomes with death as a competing event. Results: Among 119 patients who met our criteria, 51 patients (42.9%) had low adherence to weekly cisplatin. Median follow up was 19.8 months (interquartile range 8.8-65.6). Low adherence to weekly cisplatin was associated with worse overall survival (adjusted hazards ratio [aHR] 2.94, 95% confidence interval [CI] 1.58-5.47, p&lt;0.001) and progression-free survival (aHR 2.32, 95% CI 1.29-4.17, p=0.005). It was also associated with worse distant failure (aHR 4.55, 95% CI 1.19-17.3, p=0.03), but not locoregional failure (aHR 1.61, 95% CI 0.46-5.58, p=0.46). KPS &lt;90 was the only variable associated with low adherence to weekly cisplatin (adjusted odds ratio [aOR] 2.67, 95% CI 1.10-6.65, p=0.03). Conclusions: Our study suggested that over 40% of patients underwent fewer than 5 weekly cisplatin cycles and that low adherence to weekly cisplatin was an independent, adverse prognostic factor for worse survival and distant failure outcomes. Those with reduced adherence to weekly cisplatin were more likely to have poor performance status. Further studies are warranted to improve the adherence to chemotherapy and outcomes.
Neoadjuvant pembrolizumab/nab-paclitaxel/cisplatin in patients with locally advanced head and neck squamous cell carcinoma: A single-arm phase II study.
Authors: Siyi Zhang, Haiqing Ma, Jiandong Zhan, Lijun Zhu, Hong-Dan Zhang, Shasha Du, Qiumei Dong, Guangyi Wang
Journal: Journal of Clinical Oncology (2024)

e18043 Background: Despite multimodality standard therapy, patients with locally advanced head and neck squamous cell carcinoma are at high risk of recurrence and distant metastasis. The safety and efficacy of immunotherapy (pembrolizumab) has been reported in patients with recurrent/metastatic HNSCC. We hypothesized that neoadjuvant chemo-immunotherapy has a positive effect on decreasing distant metastasis, preserving organ function and extending survival time. Methods: In this prospective, non-randomized, single-arm phase II clinical trial, patients meeting the inclusion criteria were treated neoadjuvant therapy with 200 mg pembrolizumab combined with 75 mg/m 2 cisplatin and 260 mg/m 2 Nab-paclitaxel per 3 weeks for 2 cycles.Patients will undergo the first radiologic imaging assessment after neoadjuvant therapy. After multi-disciplinary team discussion, patients with Partial Response (PR) but the maximum diameter of tumor &gt; 3cm or stable disease (SD) or progressive disease (PD) receive surgery and standard adjuvant therapy. On the other hand, patients with PR and maximum tumor diameter ≤ 3cm or Complete Response (CR) receive definitive CRT. Evaluation was performed 3 months after definitive CRT and patients with high-risk factors need maintenance treatment. Primary outcomes are objective response rate (ORR), safety, rate of organ preservation. Results: A total of 31 patients were enrolled with a median follow-up of 6.6 months (1.4-20.2m). The baseline characteristics were shown in the table. Among 31 LA HNSCC patients with 2 cycles of neoadjuvant therapy, ORR was 64.52% (20/31) and DCR was 100%. 10patients underwent surgery with R0 resection, and 17 patients received definitive CRT,4 patients refuse surgery or CRT and out of trial. There was 20/31 (64.5%) organ function preservation. Among those with definitive CRT, no recurrence or distant metastasis occurred. In this trial, there's no Grade≥3 treatment-related adverse events. One patient died due to cardiacarrest and the correlation with study cannot be evaluated. Conclusions: Neoadjuvant chemo-immunotherapy contributed to good ORR and organ function preservation, and generally tolerated in LA HNSCC. This study is ongoing. And we look forward to demonstrating that neoadjuvant immunochemotherapy is expected to improve long-term survival of LA-HNSCC. Clinical trial information: NCT05272696 . [Table: see text]
Is early inclusion of neratinib with HER blockers possible in the treatment of stage 4 HER2 positive cancer?
Authors: Zilola Avazovna Olimova
Journal: Journal of Clinical Oncology (2024)

e13019 Background: The management of the patients with breast cancer and choosing the most effective therapy still remains a challenge, but an achievable goal. 30-50% of the patients with stage IV HER2-positive breast cancer have an increased risk of developing brain metastases. In most patients, effective therapy for Her2+ BC does not reach the CNS due to the blood-brain barrier, which, in turn, can lead to cancer metastasis to the brain. Trastuzumab, Pertuzumab poorly penetrates the BBB, however the treatment regimens with the inclusion of trastuzumab increase life expectancy in patients with HER2+ BC with CNS metastases, mainly due to controlling of extracranial lesions. In contrast, neratinib penetrates the BBB well, and its combination with capecitabine produces responses in intensively pretreated patients, especially in cases where the only site of disease progression is the CNS. Our study was to directly compare the efficacy and safety of Neratinib plus Trastuzumab and Docetaxel(N+TDtx) and Pertuzumab plus Trastuzumab. Methods: This study involved 43 patients, among which 28 received (N+TDtx) -1 st group and 15 received (N+TDtx) - 2 nd group. A median number of 6 cycles were delivered in the two treatment arms, followed by Trastuzumab. Results: The primary endpoint was RFS and EFS. The median RFS was not reached in 2 nd group at a median follow-up of 18.7 months, because of brain metastasis, disease progression and death of 23 (82%) patients. However, the 12-month RFS rate was significantly higher in the 1 st group than in the 2nd 98% and 65%, respectively (hazard ratio [HR], 0.72; 95% CI, 0.56-0.93; P =.012). With median follow up of 36.4 months, neoadjuvant N+TDtx reduced the risk of disease recurrence, brain metastasis, progression or death by 98%, demonstrating a landmark three-year event-free survival (EFS) rate of 57% with N+TDtx, followed by trastuzumab compared to 17% with TDtx, followed by trastuzumab (Hazard Ratio [HR], 0.68; 95% Confidence Interval [CI], 0.49 to 0.93). The most frequent adverse event in the Neratinib arm was diarrhea, which was manageable with prophylactic treatment with loperamide. Conclusions: Neratinib, has shown that it was able to prevent brain metastases and demonstrated benefit in recurrence - free survival and event-survival in combination with Trastuzumab and Docetaxel over (PT+Dtx) for patients without brain metastases.
Error in Figure 1
Journal: JAMA Network Open (2024)

Error in Figure 1 In the Original Investigation titled "Association of Early Pregnancy Perfluoroalkyl and Polyfluoroalkyl Substance Exposure With Birth Outcomes," 1 published May 31, 2023, there was an error in Figure 1.The difference and 95% CI values in panel A (PFOA) should have been presented in panel B (PFOS), those in panel B should have been presented in panel C (PFNA), and those in panel C should have been presented in panel A. This article has been corrected. 1
Clinical efficacy of pyrotinib combined with stereotactic radiosurgery in HER2-positive breast cancer brain metastases.
Authors: Junjie Zhen, Shoaib Bashir, Yanying Yang, Hui Wang, Mingyao Lai, Linbo Cai
Journal: Journal of Clinical Oncology (2024)

e13017 Background: Up to 50% of patients with breast cancer (BC) and human epidermal growth factor receptor 2 (HER2) positive present with disease progression in brain metastases (BM). Pyrotinib, an oral irreversible pan-HER receptor tyrosine kinase inhibitor, has shown efficacy in active central nervous system(CNS) metastases. However, clinical efficacy of pyrotinib combining with stereotactic radiosurgery (SRS) in BCBM is unclear. Methods: This retrospective, observational study collected data from 52 HER2+ BC patients with brain metastasis who received pyrotinib-based therapy in Guangdong Sanjiu brain hospital from 2019 to 2023. Among these patients, 36 received pyrotinib-based therapy combining with SRS concurrently, or within 1 months. Age, stage at diagnosis, dates of BM, primary tumor subtypes, prior systemic therapy, CNS-directed local therapy, the objective response and survival status were collected. The assessment of adverse effects was based on CTCAE 4.0. Results: 34 patients were evaluable for efficacy (median age: 51.5). With a median follow-up duration of 19.6 months, 1 patient (0.3%) achieved CR, while 27 patients (79.4%) had PR, resulting in an ORR of 82.3%. The median CNS PFS was 13.2 months (95% CI, 4.9-21.7). Median overall survival (OS) was 22.6 months (95% CI, 17.5-27.6). The most common grade 3 or worse treatment-emergent adverse event was diarrhea (6 [17.6%]). Conclusions: Our results suggest that pyrotinib combining with SRS is associated with promising efficacy and a satisfactory safety profile for Her2+ breast cancer brain metastases.
Can elective neck dissection for oral cancers be planned based on depth of invasion?
Authors: Kinjal Shankar Majumdar, Rajkumar Kottayasamy Seenivasagam, Manu Malhotra, Abhinav Thaduri, Achyuth Panuganti
Journal: Journal of Clinical Oncology (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 8 th 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; &gt;5 mm and ≤10 mm; &gt;10 mm) according to the AJCC TNM 8 th 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&lt;0.001). DOI did not show a strong correlation with pN status (pN0 vs pN+) either (rpb=0.27; p&lt;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&lt;0.001). ANOVA with post hoc Bonferroni showed statistical significance only for DOI &gt;10 mm group (p&lt;0.001 for DOI ≤5 mm; p=0.02 for DOI &gt;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 &lt;4 mm.
The efficacy and safety of trastuzumab biosimilar HLX02 compared with reference trastuzumab plus pertuzumab in combination with chemotherapy as the first-line treatment for HER2 positive metastatic breast cancer: A real-world study in China.
Authors: Ying Yan, Huiping Li
Journal: Journal of Clinical Oncology (2024)

e13016 Background: Dual-targeted anti-HER2 therapy with trastuzumab (H) and pertuzumab (P) significantly improves outcomes in HER2-positive breast cancer and has become the first-line standard treatment for patients with advanced HER2-positive breast cancer in China in 2019 based on the results of the CLEOPATRA and PUFFIN study. HLX02 (Zercepac) was the first trastuzumab biosimilar manufactured in China. Here, we present the first real-world comparison of HLX02 versus reference trastuzumab (RTZ) and pertuzumab with chemotherapy as the first-line treatment for HER2-positive metastatic China.Between January 2019 and August 2023, 121 patients with HER2-positive MBC patients were enrolled at Beijing Cancer Hospital in China. These patients received HLX02 or RTZ in combination with pertuzumab and various chemotherapies as first-line treatment. We retrospectively analyzed survival outcomes, efficacy, and adverse events. Methods: Between January 2019 and August 2023, 121 patients with HER2-positive MBC patients were enrolled at Beijing Cancer Hospital in China. These patients received HLX02 or RTZ in combination with pertuzumab and various chemotherapies as first-line treatment. We retrospectively analyzed survival outcomes, efficacy, and adverse events. Results: Both groups, 68 received RTZ and 53 received HLX02, showed similar characteristics of age, disease status (de novo or recurrent), metastatic sites (visceral or non-visceral), and treatment history. A total of 118 (97.5%) received trastuzumab plus pertuzumab combined with chemotherapy as the first-line palliative therapy, with a median number of 6 cycles in each group. Taxanes were the most commonly used chemotherapy regimen in both groups (91.2 vs. 92.5%), including nab-paclitaxel (44.1 vs. 45.3%), docetaxel (41.2 vs. 17.0%), paclitaxel (5.9 vs. 30.2%). With a median follow-up of 15.0 months (range 1.0 - 58.0), the results showed no significant difference in PFS between the RTZ and HLX02 arms (median PFS: 22.0 vs. 19.0 months, p=0.900). Additionally, the efficacy outcomes, including objective response rate (ORR), disease control rate (DCR), and safety profiles did not show significant differences between the two groups. Among 121 patients, 20 patients (16.5%) experienced CNS progression. For these patients, the median time from the first-line therapy to the CNS progression was 15.0 months (95% CI 12.8 - 17.2). Conclusions: The real-world data suggest similar efficacy and safety of HLX02 and RTZ plus pertuzumab with different chemotherapy regimens as the first-line treatment for patients with HER2-positive advanced breast cancer patients in China. Overall, the PFS was consistent with the CLEOPATRA trial in both groups, and there was no new safety signal.
Electronic Health Record Usage Among Surgeons—The Gender Gap
Authors: Angelena Crown, Kathie-Ann Joseph
Journal: JAMA Network Open (2024)

Karen Malacon, BA; Gavin Touponse, BS; Ezra Yoseph, BS; Guan Li, BS; Pingho (Janet) Wei, RN, MPH; Kimberly Kicielinski, MD, MSPH; Lara Massie, MD; Theresa Williamson, MD, MPH; Summer Han, PhD; Corinna Zygourakis, MD