tbuckley/cabot-search huggingface dataset:
Impact of next generation sequencing in high grade glioma management.
Authors: Simon Barry, Yazan Hani Mustafa, Carol McGibney, Laura Royo, Martin Higgins, Wail Mohammed, Mahzar Iqbal, Chris Lim, Michael Janssen, Niamh Bermingham, Muhammad Faisal Jamaluddin, Michael O'Sullivan, Mahmoud Kamel, Seamus O'Reilly, Richard Martin Bambury, Jack Gleeson
Journal: Journal of Clinical Oncology (2024)

e14031 Background: Recent advances in genomic profiling have improved our understanding of the molecular pathogenesis of high grade gliomas. Increased availability of high-throughput Next Generation Sequencing (NGS) allows the identification of genetic alterations which could direct personalized cancer treatments for HGG patients. Methods: All patients with high grade glioma (WHO Grade ≥3 glioma by 2016 or 2022 classification) in our institution, who underwent NGS testing between 2019-2023, were identified from a prospectively maintained electronic database. NGS results, from the Oncomine Precision Assay, a multi-gene panel which tests for 50 different mutations, were collated. Medical records were systematically reviewed to collect demographic, treatment and survival data. Alterations detected on NGS were characterized using the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT). Results: 53 patient samples underwent NGS testing (34 males [64%]; 19 females [36%]). Median age at diagnosis was 52 years (range: 20-72 years). Thirty patients (57%) had an ECOG PS 1 at first clinical review. 18 tumors (34%) were found to have MGMT promoter hypermethylation. 28 patients (53%) were found to have potentially actionable alterations according to the ESCAT scale; 19 (35%) EGFR mutations (ESCAT IIIA level evidence) were detected, 5 PIK3CA (9%) mutations (ESCAT IIIA), 3 FGFR3 (6%) alterations (ESCAT IIB), 2 patients with CDK 4 (4%) copy number gain (ESCAT IIIA), 2 PTPRZ1-MET (4%) fusions (ESCAT IIIA) and 1 BRAF V600E (2%) mutation (ESCAT IB). 4 patients were found to have multiple mutations on NGS. 1 sample had insufficient tissue for analysis. 2 patients (4%) were considered for targeted therapy based on NGS results (1 BRAF V600E mutation and 1 FGFR3 alteration) but both deteriorated in advance of commencing treatment. One patient received nivolumab for MSI-H recurrent GBM (ESCAT IIIB) but progressed within 3 months of commencing treatment. Conclusions: Despite advances in our understanding of the pathogenesis of these high grade gliomas and improved awareness of molecular targets, the delivery of targeted therapy to patients with HGG remains challenging. Rapid access to targeted therapy via compassionate access programmes and improved availability and access to clinical trials for patients with rare cancers and molecular alterations, is paramount.
Health state utility assessment for low-grade glioma.
Authors: Debarati Bhanja, Hannah E. Wilding, Kyle J. Tuohy, Ahmad Ozair, Nima Hamidi, Leonardo Macedo Filho, Liz Salmi, Bethany Kwan, Feng Xie, Carlos Velásquez, Michael J. Glantz, Manmeet Singh Ahluwalia, Alireza Mansouri
Journal: Journal of Clinical Oncology (2024)

e14039 Background: Low-grade gliomas (LGGs, WHO Grade II gliomas) undergo malignant transformation, portending a median survival of 5-15 years. Though resection and adjuvant therapies have significantly improved survival, there are increased risks of long-term neurological decline and treatment-related side effects. As a result, not only quantity but also quality of life (QoL) must be considered when appraising therapeutic paradigms. Health state utility assessments can quantify society’s perceptions of given health states, supporting quality-adjusted life years (QALYs) and cost-effectiveness analyses. The primary and secondary objectives were to calculate LGG health states utility values (UVs) and interpret differences between health states, respectively. Methods: Health state descriptions were developed from a comprehensive literature review, expert input, and focus groups involving neuro-oncology providers and patient advocates. Healthy, adult participants were surveyed through an online REDCap form. Two preference elicitation techniques, visual analog scale (VAS) and time trade-off (TTO), were used to derive UVs of ten LGG health states. UVs are anchored at 0 representing death and 1 for perfect health. Mann-Whitney U tests compared UVs across health states. Results: Ninety-eight participants were included. Most participants were male (52%), aged 18-29 (81.6%), and White or Asian (78%). Stable LGG had the highest UVs (Mean [SD]: VAS- 0.64 [0.21]; TTO- 0.54 [0.42]) compared to Progressive LGG (VAS- 0.44 [0.26], p&lt;0.0001; TTO- 0.36 [0.37], p&lt;0.0001), Stable LGG with Chemoradiation (VAS- 0.43 [0.23], p&lt;0.0001; TTO- 0.32 [0.34], p&lt;0.0001), and Stable LGG with Motor (VAS- 0.45 [0.23], p&lt;0.0001; TTO- 0.23 [0.32], p&lt;0.0001) and Language (VAS- 0.52 [0.22], p&lt;0.0001; TTO- 0.43 [0.40], p=0.04) Deficits. Progressive LGG UVs were not statistically different from those in Progressive LGG with Motor (VAS- 0.43 [0.23], p=0.69; TTO- 0.32 [0.34], p=0.73), Language (VAS- 0.43 [0.23], p=0.62; TTO- 0.32 [0.34], p=0.60), or Visual (VAS- 0.43 [0.23], p=0.78; TTO- 0.32 [0.34], p=0.60) Deficits. Radiation negatively impacted UVs, as UVs of Stable LGG with Chemoradiation (VAS- 0.43 [0.23]; TTO- 0.32 [0.34]) were significantly lower than UVs of Stable LGG with Chemotherapy alone (VAS- 0.43 [0.23], p=0.018; TTO- 0.32 [0.34], p=0.28) on VAS. Conclusions: These are the first-ever reported LGG health state UVs. These data will enable future QALY and cost-effective analyses, which have increasing importance as new investigational therapies become available for LGG.
A propensity-matched analysis of the efficacy and safety of neoadjuvant inetetamab and pertuzumab with paclitaxel and carboplatin (TCbIP) on locally advanced HER2-positive breast cancer.
Authors: Mingxia Jiang, Yue Chai, Jiaxuan Liu, Maiyue He, Yipeng Wang, Yang Xue, Zeyu Xing, Mengqi Zhang, Shihan Zhou, Fei Ma, Jiayu Wang, Peng Yuan, Binghe Xu, Qiao Li
Journal: Journal of Clinical Oncology (2024)

e12609 Background: Inetetamab is an Fc segment-modified innovative anti-HER2 monoclonal antibody. It has been proven to be effective and safe in HER2-positive advanced breast cancer. However, its efficacy and safety in the neoadjuvant treatment of HER2-positive locally advanced breast cancer (LABC) remains to be validated. This study aimed to evaluate the efficacy and safety of Inetetamab-based neoadjuvant therapy (TCbIP). Methods: In this prospective cohort study, we investigated the efficacy and safety of TCbIP in neoadjuvant therapy for HER2-positive LABC, and compared with TCbHP regimen (trastuzumab combined with pertuzumab, paclitaxel, and carboplatin) with propensity score matching (PSM). Thirty-four patients (clinical stage IIA-IIIC, HER2-positive LABC) were prospectively enrolled in this study and treated with the TCbIP regimen. The primary endpoint was total pathological complete response (tpCR). Adverse events (AEs), objective response rate (ORR), and near-pCR were key secondary endpoints. Results: The pCR rate of 28 patients who finished surgery was 60.7%, and was comparable and slightly higher (60.7% vs. 53.6%, P = 0.510) than the TCbHP group in PSM. The ORR was 96.4% and DCR reached 100.0%. The most common ≥grade 3 AE was neutropenia (21.4% vs. 11.9%, P = 0.350). No significant reduction in left ventricular ejection fraction was observed, and no patient withdrew from treatment due to AEs. Conclusions: Neoadjuvant therapy with TCbIP resulted in good efficacy and safety in patients with HER2-positive LABC, and might be another promising option for neoadjuvant treatment. Clinical trial information: NCT05749016 .
The predictive role of Ki67 in pathological complete response (pCR) and invasive disease-free survival (IDFS) in HER2-positive breast cancer: A retrospective study of 246 cases.
Authors: Laura Weydandt, Saida Agabejli, Massimiliano Lia, Pauline Wimberger, Bahriye Aktas, Theresa Link
Journal: Journal of Clinical Oncology (2024)

e12610 Background: While Ki67 is a routine diagnostic measure for early hormone receptor positive breast cancer, it is not integrated into the standard procedure for patients with Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer patients, given the substantial risk linked to HER2 expression alone. Consequently, the predictive significance of Ki67 in achieving pathological complete response (pCR) or invasive disease-free survival (IDFS) in this subgroup remains uncertain. Methods: This retrospective, bi-centric analysis focused on HER2-positive early breast cancer patients undergoing neoadjuvant chemotherapy from 2015 to 2023. We assessed the correlation between Ki67 values and the achievement of pathological complete response (pCR, defined as ypT0/is, pN0). Multivariable logistic regression analyzed the independent association of various clinical parameters, including Ki67, with pCR. Ki67 values were categorized into risk groups (low &lt;15%, intermediate 15.1-35%, high &gt;35%) following the GepardTrio data [1]. Kaplan-Meier estimator calculated differences in overall and invasive disease-free survival. Results: The study included 246 HER2-positive early breast cancer patients with known Ki67 expression, followed for a median of 42 months. The median age was 52 years. Final nodal status was pN0 in 80.5%, pN1 in 15%, and pN2 in 3.3%. Hormone receptor positivity was observed in 66% of patients. 147 patients (60%) achieved pCR. Median Ki67 was 30. When categorized, 13% were low, 41.5% intermediate, and 45.5% high risk. No correlation between Ki67 and pCR was observed (p=0.25). HER2 IHC score 3+ significantly increased pCR compared to IHC 2+ (62.2% vs. 44.6%, p=0.023). Hormone receptor-positive tumors had a lower pCR rate (52.7% vs. 72.4%, p=0.0016. 5-year overall survival was 96.5% for pCR and 83.8% for non-pCR (p=0.008). 5-year invasive disease-free survival showed no difference between low Ki67 (89.5%), intermediate Ki67 (79.9%), and high Ki67 (80.9%) groups (p=0.77). Conclusions: In this study, Ki67 did not predict pCR in HER2-positive breast cancer, providing no additional clinical value. HER2 IHC score and hormone receptor status were predictive indicators for pCR. Ki67 expression appears to lack additional value in HER2-positive breast cancer, considering resource implications. 1. Denkert C et al: Ann Oncol. 2013 Nov;24(11):2786-93. doi: 10.1093/annonc/mdt350. Epub 2013 Aug 22. PMID: 23970015.
High-dose furmonertinib in combination with intraventricular chemotherapy for <i>EGFR</i> exon 20 insertion mutated lung adenocarcinoma with leptomeningeal metastasis.
Authors: Shencun Fang, Hehui Fang, Ting Xu, Liangfeng Yang, Xiaoyue Wang, Na Liu, Xing Zhang, Bei Zhang
Journal: Journal of Clinical Oncology (2024)

e20555 Background: Leptomeningeal metastasis (LM) is a severe complication of advanced lung adenocarcinoma (LUAD) and always has a dismal prognosis. EGFR exon 20 insertion ( EGFR 20ins) is the third most common EGFR mutations; however, there are currently no reports focusing on LM with EGFR 20ins, and the optimal therapy for these patients remains unclear. This retrospective study aimed to evaluate the efficacy and safety of high-dose furmonertinib in combination with intraventricular chemotherapy in EGFR 20ins mutated LUAD patients with LM. Methods: Weretrospectively enrolled 10 LUAD patients with LM who had failed multiline treatment between May 2021 and June 2023 at Nanjing Chest Hospital. All of them had confirmed EGFR 20ins by next generation sequencing. All patients received furmonertinib in combination with intraventricular chemotherapy via the Ommaya reservoir. Furmonertinib was taken at 160 mg once daily. The chemotherapy regimen consisted of 30mg pemetrexed and 5 mg dexamethasone administered twice weekly for 2 weeks during the consolidation phase, followed by a maintenance phase every 3-4 weeks until disease progression or unacceptable toxicity, or patient refusal. Results: The median age was 53.5 years (range: 39-66), and six (60%) were males. Four patients (40%) had an ECOG of 3, and six patients (60%) had an ECOG of 4. The intracranial ORR (iORR) was 60% (6/10) and intracranial DCR (iDCR) was 90% (9/10). The ECOG PS improved in 80% patients after treatment. With a median follow-up of 9.3 months, the median intracranial progression-free survival (iPFS) was 7.3 months (95% CI, 3.3-NR) and the median overall survival (OS) was 8.8 months (95% CI, 4.9-NR), respectively. Treatment related adverse events of ≥ grade 3 occurred in only 2 patients, which were nausea and rash. Conclusions: Furmonertinib in combination with intraventricular chemotherapy is a tolerable treatment with breakthrough clinical efficacy for LUAD patients with LM harboring EGFR 20ins.
Interchangeability of anti-PD1 antibodies in patients (pts) with metastatic NSCLC.
Authors: Darya Kravchuk, Mikhail Fedyanin, Borovkov Ivan, Fedor Vladimirovich Moiseenko, Lyudmila Zhukova, Ilya Pokataev, Anastasia Rays, Viacheslav Chubenko, Nikita Volkov, Kirill Ivanilov, Elena Glazkova
Journal: Journal of Clinical Oncology (2024)

e20553 Background: PD-(L)1 inhibitors are approved immunotherapy agents in treatment for mNSCLC, however, limited data exists about switching between different anti-PD1 antibodies. Our study aimed to evaluate the safety and efficacy of the interchangeability of nivolumab, pembrolizumab, and atezolizumab in patients (pts) with mNSCLC in the 2nd and 3rd line. Methods: We retrospectively evaluated data of pts with mNSCLC treated in four oncology centers in Moscow and SaintPetersburg (Russia). Inclusion criteria were as follows: histologically confirmed mNSCLC with no driver mutations, performance status ECOG 0-2, monotherapy of anti-PD(L)1 antibody, and switching to another PD(L)1 inhibitor for any reason except progression disease or toxicity after initiating of immunotherapy. The primary end-point was progression-free survival (PFS), and secondary end-points were the rate of all grades and grade 3-4 adverse events (CTC AE 5.0). A sample size of 83 achieves 80% power to detect an equivalence difference of 15% in 3-months PFS after the change of anti-PD1 antibody with a one-sided significance level of 0,05. Results: A total of 103 patients (27% female) were included with a mean age of 66 years (33-93). 0-1, 2, and ≥3 organs with metastases have 70 (68%), 17 (17%), and 16 (16%) pts, respectively. Performance status ECOG 0, 1, and 2 was in 16 (16%), 70 (68%), and 17 (17%) pts, respectively. 50 (48%) patients received pembrolizumab, 40 (39%) pts received nivolumab, and 13 (13%) pts – atezolizumab. 48 (47%) pts were switched to atezolizumab, 28 (27%) pts were switched to nivolumab, 26 (25%) pts – to pembrolizumab. The median duration of treatment with the first anti-PD(L)1 antibody was 6 months (1-53 months), with the second PD(L)1-inhibitor was 3 months (1-41 months). Within 3 months after 1 replacement of the drug, there were 77 (74,7%) pts without progression. With the median follow-up of 8 months (1-41), the estimated 3-month PFS was 79,3%. The efficacy of switching was not associated with the agent (HR 0,97, 95CI 0,68-1,38, p = 0,9). There were 2 cases of AEs of 3-4 grades when switching to the second drug. Conclusions: Switching from one anti-PD(L)1 antibody to another in pts with mNSCLC is possible in case of limited access to PD(L)1 inhibitors.
Demographic disparities influencing survival of patients with glioblastoma.
Authors: Fathima Shehnaz Ayoobkhan, Mohammad Arfat Ganiyani, Manas Pustake, Shahzaib Ahmad, Vivek Podder, Shreyas S Bellur, Prashant Howal, Aditya Shah, Judie R. Goodman
Journal: Journal of Clinical Oncology (2024)

e13795 Background: Glioblastoma Multiforme (GBM) is an aggressive brain tumor with a life expectancy of less than a year post-diagnosis despite multimodal therapy. Recent Advancements have significantly prolonged the survival period. However, barriers still exist in survivorship care for minority populations. We aim to delve deeper into understanding these disparities in survival outcomes based on demographic characteristics. Methods: We included patients diagnosed with Glioblastoma Multiforme in the National Cancer Database from 2004-2021. Demographic characteristics were taken into account. Kaplan Meir curve and Log-rank test were utilized to compare survival rates in different groups. Results: A total of 169793 patients were identified from 2004-2021 with an increased incidence in the age groups 64-74. Overall survival has increased steadily since 2011 (2004-2011 OS 8.84 months Vs 10.55 months from 2011-2021 p-value=0.058). Age is an independent predictor of survival. The younger the patient, the better the survival period. Young adults (&lt;50 years) have a better OS of 19.22 months with a decline in age 50-64 (13.22 months), and age 64-74(8.18 months, p value &lt;0.001). Worsen OS is seen in the geriatric population (3.75 months). African Americans (AA) have a better survival period as opposed to Whites (10.91 months Vs. 9.63 months, p value &lt;0.001). Multivariate analysis revealed that age, race and the time frame of diagnosis (before 2011 vs after 2011) have a major role in predicting survival. Conclusions: Demographic disparities seen in the survival patterns, with worse outcomes seen in elderly, White people. Future research directions should be emphasized in the marginalized group White, elderly population. [Table: see text]
Mapping models of care for children, adolescent and young adult cancer survivors: A scoping review.
Authors: Larissa Nekhlyudov, Natalie Bradford, Carla Thamm, Xiomara Skrabal Ross, Ray Chan
Journal: Journal of Clinical Oncology (2024)

e13793 Background: Young cancer survivors, with decades of life ahead, encounter substantial risks for treatment-related late effects. Achieving optimal outcomes requires a comprehensive multi-dimensional approach. This scoping review aimed to systematically map the evidence on models of survivorship care for Child (0-14) and Adolescent and Young Adult (AYA, 15-39) cancer survivors aligning with the Framework for Quality Cancer Survivorship. Methods: Conducted according to PRISMA extension for scoping reviews, this study systematically searched MEDLINE, CINAHL and Embase for English articles from Jan 2006 to Jan 2024. Inclusion criteria were studies describing patient and health service domain for Child and AYA cancer survivorship models of care. Dual processes were used for article screening, selection, and data extraction. A deductive analysis, using Content Analysis informed results, presented in a narrative synthesis. Results: Of the 5,298 records screened 38 described Child and 10 described AYA models of care. The majority were cohort and cross-sectional studies from the USA, Canada, and the UK representing 6,101 Child and 5,283 AYA cancer survivors. Across these diverse studies, a broad range of outcomes were identified with most domains of the Framework represented. No model of care described more domains than another. Across the 13 possible elements of care and outcomes, most (68%) reported on less than five of these. The domains most represented included elements of care rather than outcomes at the service level such as the clinic structure (52%), communication and decision making (52%) and patient/carer satisfaction (50%). At the patient level, quality of life outcomes and assessment and management of physical symptoms were represented in 40% of studies. There were few studies reporting on health promotion (23%), chronic conditions (13%), mortality and healthcare utilization (5% each) and none reported on costs. In terms of outcomes, oncologist long-term follow up care showed higher adherence to risk-based recommendations compared to primary care models in some studies. Other studies suggest a shared care model increases adherence and decrease lost to follow-up. At the service level, high satisfaction with care was common in all models. Overall, there was not enough to evidence to support one model over another in either Child or AYA survivorship care. Conclusions: Despite decades of research in survivorship care, there is not enough evidence about the effectiveness and efficiency of different models of care. No single model stands out as superior, and there are notable gaps in understanding the economic and value proposition of different models. Addressing these gaps is crucial for the future development, and provision of quality survivorship care tailored for this patient population.
Characterizing vaginal stenosis in female cancer survivors.
Authors: Olivia Mihulka, Melissa Curran, Tizeta M. Wolde, Jessica Firdman Moore, Kristin E. Rojas
Journal: Journal of Clinical Oncology (2024)

e13800 Background: Vaginal stenosis is an underreported and undertreated sequelae of cancer treatment that leads to pain with sexual activity and inability to tolerate pelvic exams. We sought to describe a population of female cancer survivors presenting with sexual health concerns and identify factors associated with presence of vaginal stenosis on genitourinary exam (GU). Methods: A retrospective analysis included 134 female cancer survivors presenting to a sexual health after cancer program in South Florida (2020-2023). Sexual function and GU anatomy disruptions were evaluated using the Female Sexual Function Index (FSFI) and Adapted Vulvovaginal Exam Score (AVES), respectively. Vaginal stenosis was defined as presence of vaginal agglutination, shortening, or scarring/adhesions on GU exam. Patients who did and did not present with vaginal stenosis were compared using Chi-squared analysis, while independent t-test analyzed FSFI and AVES scores. Results: Of 134 patients, 116 met criteria for inclusion and underwent a GU examination. Median age was 45 (23-75). Race, ethnicity, menopausal status, cancer type, and treatment type were similar between groups. The rate of vaginal stenosis in patients with breast cancer was 13.4%, gynecologic cancer was 27.2%, and 28.6% with other cancer types (including gastrointestinal, hematologic, sarcoma). Higher median AVES scores, which denote more severe GU exam disruptions, were found in patients with vaginal stenosis compared to those without (13 vs 5; p&lt;.001). While overall FSFI scores were similar between groups, median FSFI pain domain scores were lower in those with vaginal stenosis compared to those without stenosis (7.8 vs 11; p=0.037). Conclusions: Factors associated with the development of vaginal stenosis in female cancer survivors are not well-described. Our analysis reveals that vaginal stenosis develops in women treated for a variety of cancer types across the age continuum. Identifying and treating this severe sequela of treatment is a critical step in improving the sexual health of female cancer survivors. Ongoing work seeks to evaluate the safety and efficacy of treatments to reverse GU exam disruptions after cancer treatment. [Table: see text]