bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment analysis of patients diagnosed with intraductal carcinoma of the prostate (IDC-P) in the US from 2000 to 2018.
Authors: Stamey Taylor , Armel Kristen , Ju Andrew W , Chen Shoujun , Navaid Musharraf , Larkins Michael Casmer , Bhatt Arjun
Published: July 2024

e17011

Background: Intraductal carcinoma of the prostate (IDC-P), considered both a distinct entity (found alone in ~3% of prostate biopsies) and negative prognostic factor of prostatic cancer (identified in ~20% of all patients with prostate cancer). IDC-P represents aggressive disease, and is associated with increased metastasis, recurrence, and prostate cancer-specific death. Given the mortality and rarity of this disease, we analyzed demographic and treatment trends of patients diagnosed with IDC-P in the US. Methods: A retrospective cohort study utilizing the Surveillance, Epidemiology, and End Results (SEER) database sponsored by the National Cancer Institute (NCI) was conducted for patients with a diagnosis of IDC-P between 2000 and 2018. Univariate, multivariate, and survival analyses were performed on demographic and treatment characteristics using 95% confidence intervals [CI] and a p-value < 0.05 indicating significance. Results: 1003 patients with complete follow-up and survival data were identified. Patients with local disease that underwent radical prostatectomy without radiotherapy (RT) had increased five-year overall survival (OS) compared those that only received RT (99% vs 75%; p<0.001); those with regional disease did not (p=0.617). No survival benefit was seen among patients that received RT in addition to radical prostatectomy compared to those treated with radical prostatectomy solely (p=0.770 for local disease and 0.909 for regional disease). Lymph node (LN) examination, performed in 33.1% of patients, yielded increased five-year OS compared to absence thereof (99% versus 73%; p<0.001). 45% of patients that had LN examined were found in a single SEER registry (California). The 2.7% of patients that received chemotherapy (CTX) saw no survival benefit in the setting of distant disease (n=14; 0% versus 78%, respectively; p<0.001). No difference was seen in five-year OS with respect to race (p=0.967) though single patients saw decreased OS compared to married ones (hazard ratio (HR)=0.83; p=0.050) and patients younger than 65 years saw increased survival (HR=0.89; p=0.002). On multivariate analysis, the interaction between stage, surgical treatment, and receipt of RT demonstrated a difference in five-year OS (p=0.020). Conclusions: This analysis demonstrates survival benefit with radical prostatectomy solely versus treatment with RT among patients with local IDC-P, and did not find benefit with CTX in patients with distant disease. The survival benefit found with LN examination may be a center- or region-specific outcome. Patient age and marital status may have implications for patient outcomes. Further investigation into specific treatments, socioeconomic factors, and disease surveillance measures for patients with prostate cancer is warranted.
Long term sequelae of testicular cancer and treatment: A point prevalence observational study.
Authors: Khan M Raheel , Kearney Sheehan Patrice , Bazin Ashley , Leonard Christine , Aleem Umair , Trainor Sebastian , Corrigan Lynda , McDermott Raymond S.
Published: July 2024

e17015

Background: Testicular cancer (TC) is a highly curable solid organ tumour, which usually occurs in the early years of life. Recent studies have observed an increase in the incidence of TC coupled with improvement in cure rates all around the world, especially in Western Europe and North America. Consequently, we have a growing population living in the survivorship phase. Many researchers have highlighted the late complications in TC survivors, linked with the different treatment modalities used for treatment. In this study, we aim to determine the point prevalence of morbidity and mortality in TC survivors at a tertiary care cancer centre in Ireland. Methods: Participants were assessed in a purpose built survivorship clinic and informed consent was obtained. All participants were 18 years or more of age at the time of assessment with a histologically confirmed diagnosis of testicular cancer over 5 years ago. Assessments included a thorough symptom review, clinical examination, blood tests and other investigations (e.g., X-ray, ECG) if required. Results: A total of 81 patients were recruited in the study from March 2023 to January 2024, with a median follow up of more than a 10 years (129 months). Chemotherapy had been given to 85% of patients and radiotherapy to 5%. All except one patient underwent orchiectomy while RPLND was performed in 17% of patients. There were 3 deaths in the survivorship phase, all related to second malignant neoplasms (SMNs). Hyperlipidaemia was the most common condition found in 55% of TC survivors, followed by raised gonadotropins (47%), low testosterone (34%) and hypertension (40%). Other conditions prevalent in our cohort were hearing impairment (26%), abnormal high glucose (8%) and renal impairment(7%). The majority of these co-morbidities were previously undiagnosed before assessment in our survivorship clinic, including 2 cases of coronary artery disease. Over 70% of hypogonadism, hyperlipidaemia, hypertension, renal impairment and high abnormal glucose were initially diagnosed in our clinic. Conclusions: Results from our study are comparable to the studies conducted in other cancer centres across Europe and the US. Second malignant neoplasms remain the major cause of mortality in this cohort but many modifiable risk factors can be diagnosed early and potentially treated to prevent morbidity. Our data strongly supports the need for specialised survivorship clinics to improve the prognosis and quality of life in TC survivors. [Table: see text]
Prognostic factors and survival in men with testicular germ cell tumors (GCT).
Authors: Zagoruiko Valentina , Semenova Anna , Abdullaeva Sheyda , Ekaterina Mureiko , Karina Khidishyan , Teletaeva Gulfiya , Novik Alexey , Latipova Dilorom , Nosov Alexandr , Semiglazova Tatiana , Protsenko Svetlana
Published: July 2024

e17018

Background: The International Germ Cell Cancer Collaborative Group (IGCCCG) has recently discovered new factors for GCT in 2021. We have estimated previously known and new prognostic factors in patients with nonseminomatous germ cell tumors (NSGCT) and seminoma treated at N.N. Petrov NMRC of Oncology. Methods: From 2011 to 2021, the study included 273 adult patients receiving standard cisplatin-based chemotherapy. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Survival was estimated using the Kaplan-Meier and Cox methods. Results: 5-year OS rates were 94%, 85% and 70% in the good, intermediate, and poor prognosis groups, respectively for NSGCT and 95% and 86% in good and intermediate prognosis groups for seminoma (p<0.05). 5-year PFS rates were 74%, 51%, and 41% for NSGCT and 76% and 62% for seminoma of the above-mentioned prognostic groups, respectively (p<0,05). Presence of pulmonary metastases (mts) (HR 0.177; 95% CI: 0.051-0.612; p=0.006), non-pulmonary visceral mts (HR 4.636; 95% CI: 1.710-12.570; p= 0.003), elevated LDH of ≥ 2.5 limit of normal (≥ 2.5 × ULN) (HR 4.107; 95% CI: 1.614-10.451; p= 0.003), treatment in high-experienced clinic (HR 0.37; 95% CI: 0.147-0.919; p=0.0032), and non-compliance with guidelines (HR 3.731; 95% CI: 1.456-9.564; p= 0.006) was significantly associated with OS in NSGCT. The presence of pulmonary mts (HR 0.15; 95% CI: 0.024-0.877; p=0.035) and elevated LDH ≥ 2.5 × ULN (HR 0.109; 95% CI: 0.015-0.775; p=0.027) were the only factors associated with poor OS in seminoma. The presence of pulmonary mts (HR 0.446; 95% CI: 0.247-0,804; p=0.007), non-pulmonary visceral mts (HR 2.668; 95% CI: 1.390-5,120; p=0.003) and treatment in high-experienced clinic (HR 1.852; 95% CI: 1.059-3.238; p=0.031), were significantly associated with inferior PFS in NSGCT. Pulmonary mts were the only significant (HR 0.301; 95% CI: 0.100-0.910; p=0.033) factor in the multivariate OS analysis for all testicular GCT. The absence of non-pulmonary visceral mts (HR 0.522: 95% CI: 0.265-0.963; p=0.019) and compliance with guidelines (HR 0.565; 95% CI: 0.309-0.910; p=0.038) were significant factors in the multivariate PFS model for all patients with testicular GCT. Conclusions: The original IGCCCG classification remains the reference for treatment decisions for testicular GCT in daily practice. Non-compliance with guidelines and treatment in high-experienced clinic could become additional poor prognostic factors.
Differences in clinical features between CA-125 and RECIST progression in patients with ovarian cancer treated with PARP inhibitors.
Authors: Ma Yana , Lv Weiwei , Bu Hualei , Kong Beihua , Song Kun
Published: July 2024

e17568

Background: The clinical features of disease progression (PD) based on Response Evaluation Criteria in Solid Tumors (RECIST) and carbohydrate antigen (CA)-125 criteria, and the impact on prognosis in ovarian cancer patients treated with poly (ADP-ribose) polymerase inhibitors (PARPi) were ambiguous. Methods: All ovarian cancer patients included in this retrospective analysis were treated with PARPi monotherapy and regularly assessed with RECIST and CA-125 criteria until disease progression was confirmed by RECIST criteria. According to the presence or absence of CA-125 PD within a 28-day period before and after RECIST PD, patients were categorized into two groups: RECIST PD group (no CA-125 PD within 28 days) and CA-125 PD group (CA-125 PD present within 28 days). Subsequently, the differences in clinical features and progression-free survival (PFS) of subsequent treatment after PARPi resistance between the two groups were analyzed. Results: A total of 139 patients were included, with 71 (51.1%) in RECIST PD group and 68 (48.9%) in CA-125 PD group. Patients in RECIST PD group had a lower proportion of lymph nodes progression (22.5% vs. 52.9%, p=0.000), and multi-sites progression (28.2% vs. 45.6%, p=0.033). Patients in CA-125 PD group had poorer benefit to subsequent chemotherapy after progression of PARPi, with a median PFS of 5.5 and 7.9 months, respectively (HR=1.44, p=0.019). The multivariate analysis showed that PARPi treatment time less than 6 months (HR=2.218, p=0.001) and RECIST PD accompanied by CA-125 PD (HR=1.766, p=0.024) were the main risk factors for PFS of subsequent treatment. Conclusions: Patients with RECIST PD but without CA125 PD have a reduced likelihood of experiencing lymph nodes progression or multi-sites progression. Conversely, patients with RECIST PD and CA125 PD simultaneously demonstrate poorer outcomes in subsequent treatment after PARPi resistance.
Genetic characteristics of cerebrospinal fluid-derived circulating tumor DNA in brain metastases of lung adenocarcinoma.
Authors: Tao Rongjie , Zhang Hui , Xu Shaohua , Li Tao , Tang Xiaoyong , Wu Jiayan , Sun Xuejiao , Zhang Chunmei , Shangguan Hong
Published: July 2024

e20503

Background: Brain metastases (BM), encompassing parenchymal metastases (PM) and leptomeningeal metastases (LM), are a common and fatal complication of advanced lung adenocarcinoma (LUAD). However, the genomic disparities between PM and LM, as determined by cerebrospinal fluid (CSF)-derived circulating tumor DNA (ctDNA), and its clinical utility as a liquid biopsy medium remain unclear. Methods: We conducted a retrospective study involving 33 patients diagnosed with BM from LUAD, comprising 16 cases with PM and 17 cases with LM, at Shandong Cancer Hospital between March 2018 and June 2021. CSF and matched peripheral blood lymphocyte samples were collected from all patients, and plasma samples were collected from 25 of them. Genomic profiles of CSF and plasma in patients with PM and LM were compared. CSF-ctDNA, plasma-ctDNA, and DNA from matched peripheral blood lymphocytes underwent next-generation sequencing (NGS) based on a 769 cancer-related gene panel. Results: A total of 363 mutations were detected in CSF-ctDNA, with 90.9% (30/33) of all LUAD patients with PM or LM showing mutations. EGFR mutations were the most common, occurring in PM samples from 56.3% (9/16) of patients and in LM samples from 76.5% (13/17) of patients, followed by other frequently mutated driver genes, including TP53 in 19 (57.6%) patients, MLH1 in 9 (27.3%) patients, and KMT2C in 8 (24.2%). Notably, EGFR 19del was more prevalent as a driver mutation in patients with LM compared to those with PM in our study, particularly the p.E746_A750del mutated subtype. Furthermore, the frequency of mutations in the mismatch repair (MMR) pathway was significantly higher in patients with LM than in those with PM. Additionally, CSF exhibited a more comprehensive profile of driver genomic mutations than matched plasma in patients with any form of BM, accompanied by a higher variation burden and detection of druggable mutations. Conclusions: CSF-ctDNA sequencing revealed distinct genomic patterns in patients with BM, particularly in LM, and could potentially enhance the management of BM patients compared to plasma.
Ultra-short circulating tumor DNA (usctDNA): A new paradigm for ctDNA liquid biopsy.
Authors: Wong David T. , Wei Fang , Lin Chien-Chung , Huang Wei-Lun , Tang Cheuk Ying , He Hua-Jun , Kim Yong , Li Feng
Published: July 2024

e20510

Background: Mononucleosomal ctDNA (mnctDNA, 157-bp, double-stranded) spearheads liquid biopsy (LB) for cancer detection, treatment and clinical care. The bottleneck of mnctDNA LB are low copy number of ctDNA and limit of detection of platform technologies. Recent discovery of ultra-short ctDNA (usctDNA, 52-54 nt, single-stranded) that harbors somatic mutations prompted us to explore the quantification and stoichiometry of usctDNA to mnctDNA in plasma and saliva of NSCLC patients. Methods: Paired plasma and saliva from 20 advanced NSCLC patients with tissue genotyped positive for L858R were processed for cfDNA extraction and quantification with Qubit and Tape Station. Digital PCR assays targeting L858R somatic mutation to generate amplicons of 57-bp (usctDNA) and 100-bp (mnctDNA) were performed by UCLA and independently by NIST. Results: Results in Table 1 revealed that three findings of usctDNA that will have potential to impact ctDNA liquid biopsy. First, the somatic mutation (L858R) is present in usctDNA. Second, The stoichiometric ratio of usctDNA to mnctDNA is similar in plasma and saliva at 1.6X. For the wild-type counterpart, the ratio is 1.1X for plasma and 0.6X for saliva. Third, the copy number of usctDNA and mnctDNA in saliva to plasma is 7.8X and 7.7X. Conclusions: Detection of tumor-associated/specific EGFR L858R somatic mutations in uscfDNA is translationally impactful, adding 1.6X of the ctDNA targets for molecular detection, effectively cumulating 2.6X of total ctDNA targets, permitting earlier cancer detection, treatment monitoring and therapy prognostication. The finding that saliva harbors 7X of the us- and mnctDNA further raises the prospect of advancing saliva ctDNA liquid biopsy for NSCLC detection as it may effectively allow 15.5X (7.8X+7.7X) ability to detect malignancy-associated ctDNA. [Table: see text]
What is a bad ALK? A scoping review of molecular markers of poor prognosis.
Authors: Chan Sze Wah Samuel , Zeng Joy , Liu Geoffrey , Jao Kevin , Juergens Rosalyn A.
Published: July 2024

e20530

Background: Patients with non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase ( ALK) rearrangements derive a significant and durable clinical benefit from tyrosine kinase inhibitors (TKI). However, a portion of patients have progressive disease as their best response and progress to death much earlier than expected which is termed primary resistance. This scoping review aims to summarize the known molecular mechanisms that underlie this lethal ALK phenotype. Methods: We performed a systematic scoping review from scientific databases such as Ovid Medline, Ovid Embase, and Cochrane Central Register of Controlled Trials. Data was extracted from the database inception to March 13, 2023. Studies included molecular markers of poor prognosis, with a focus on TP53, variant 3 re-arrangements, and reports of poor clinical response to TKIs (defined as progression-free survival less than 3 months on 1st line TKI or overall survival less than 2 years from exposure to 1st line TKI). 2nd generation and 3rd generation ALK TKI clinical trial data were also included. Results: A total of 4360 studies were screened and 136 studies were included. Numerous studies implicated the negative prognostic role of variant 3 likely mediated through the acquisition of on-target resistance mutations compared to other variants. TP53 mutations were also associated with a worse prognosis and implicated with greater chromosomal instability and mutational burden. Furthermore, reports of both variant 3 and TP53 mutations together were associated with even worse survival suggesting both molecular mechanisms combined can confer primary resistance phenotype. Other mediators of primary resistance included aberrations in cell cycle regulators such as CDKN2A/B loss, mutations in cell signalling pathways such as the PI3K/ AKT/mTOR pathway, deficiencies in DNA repair mechanisms, and uncommon fusion partners. Consistent with these prior studies, comprehensive genomic analysis from clinical trial data of 2nd generation and 3rd generation TKIs was unable to identify a singular genomic signature that underlies this lethal phenotype. However, a general trend from the literature suggested that the combination of multiple aberrations is likely necessary to confer a primary resistance phenotype, though the relative contribution of each somatic mutation likely will vary. Conclusions: This scoping review highlights that in NSCLC, the lethal ALK phenotype is likely composed of a heterogeneous population of various combinations of poor prognostic factors including variant 3, mutations in cell cycle regulators and other aberrations in cell signalling pathways. There remains an unmet need for a genomic assay to integrate all these various molecular markers to predict the lethal ALK phenotype.
Impact of concomitant H1 antihistamine administered during initiation of immune checkpoint inhibitor therapy on survival outcome and safety in patients with advanced primary lung cancer.
Authors: Zhang Weihong , Li Bingxue , Liu Liang , Ren Xiubao
Published: July 2024

e20532

Background: Antihistamines alleviate the side effects of antitumor drugs and have some antitumor effects. However, they have rarely been tested in combination with other antitumor therapies, especially immunotherapy. Methods: We compared the progression-free survival (PFS) and overall survival (OS) of patients with advanced primary lung cancer (stage III or IV) receiving immunotherapy with H1 antihistamine diphenhydramine alone (n = 40) or in combination with H2 antihistamine cimetidine (n = 69) [experimental group] to those receiving immunotherapy alone (n = 75) or with a H2 antihistamine cimetidine (n = 27) [control group]. We used the inverse probability of treatment weights (IPTW) to balance the two groups. Kaplan Meier curves were used to compare OS and PFS between the two groups. Cox regression analyses were used to describe the association between patient characteristics and OS or PFS. Results: The experimental group comprised 109 patients, while the control group comprised 102. The median PFS (mPFS) was 12.7 months in the experimental group and 4.3 months in the control group (HR 0.46, 95% CI 0.35-0.63, P < 0.001). The median OS (mOS) was 32.8 months in the experimental group and 18.1 months in the control group (HR 0.63, 95% CI 0.44-0.91, P = 0.038). In the experimental group, patients treated with only H1 antihistamine had longer mPFS and mOS as compared with those who received H1 plus H2 antihistamines (mPFS: 18.0 months vs. 6.8 months, HR 1.40, 95% CI 0.26-0.63, P < 0.001; mOS: not reached vs. 26.6 months, HR 0.55, 95% CI 0.32-0.94, P = 0.030). In the control group, patients who received no antihistamine had longer mPFS and mOS compared to those who received only H2 antihistamines (mPFS: 5.8 months vs. 4.1 months, HR 0.44, 95% CI 0.29-0.67, P < 0.001; mOS: 25.5 vs. 16.9 months, HR 0.61, 95% CI 0.37-1.00, P = 0.049). After multivariate analyses, H1 antihistamine was the independent good prognostic factor for PFS and OS (PFS: HR 0.44, 95% CI 0.31-0.65, P < 0.001; OS: HR 0.62, 95% CI 0.39-0.99, P = 0.047). Conversely, H2 antihistamine was the independent poor prognostic factor for PFS and OS (PFS: HR 2.44, 95% CI 1.67-3.57, P < 0.001; OS: HR 2.38, 95% CI 1.49-3.70, P < 0.001). After IPTW, the rate of any grade of irAEs in the experimental group was 52.4%, while that of the control group was 69.2% ( P = 0.015), including 4.5% for irAEs grades ≥3 in the experimental group and 25.9% for irAEs grades ≥3 in the control group ( P = 0.003). Conclusions: Concomitant H1 antihistamines can not only improve immunotherapy efficacy but also reduce irAEs. Concomitant use of H2 antihistamines may shorten PFS and OS time.
Single-cell transcriptome in the examination of the molecular characteristics of macrophages in lung cancer brain metastasis.
Authors: Zhao Jixing , Yan Wu , Huang Wencong , Li Yongsheng , Jing Zhang , Li Yingqiang , Guo Jia
Published: July 2024

e20546

Background: Brain metastasis is one of the most common distant metastasis types in lung cancer patients. Its mechanism involves multiple factors, including cell-cell interactions, immune evasion, and the influence of the microenvironment. Single-cell RNA sequencing technology has significantly advanced our understanding of tumors at a single-cell resolution. It enables an in-depth understanding of the expression profiles of metastatic cells in brain tissue, providing potential predictive biomarkers for future monitoring, diagnosis, and effective treatment. Methods: We collected 50 samples from the GEO database, including 17 normal lung samples, 17 lung cancer samples, and 16 brain metastasis samples. We used the MNN method for batch correction and performed differential analysis using findAllMarkers and FindMarkers. Additionally, we conducted enrichment analysis using ClusterProfiler. Results: After batch correction and re-clustering of the macrophages, we identified 9 clusters. Based on their biological functions, they were classified into 5 macrophage subtypes: RTM_macro, Angio_macro, SEPP1_macro, Prolif_macro, and Mono_like. The angiogenic macrophages (Angio_macro) were most prominent in lung cancer brain metastasis samples (52%), followed by lung cancer (25%), and least present in normal samples (17%). Enrichment analysis revealed that iron death, antigen processing and presentation, and endoplasmic reticulum protein processing were more enriched in brain metastasis. This correlates with the high proportion of angiogenic macrophages present in the brain. The SEPP1_macro subtype showed high expression of SEPP1 and VCAN, genes associated with angiogenesis. Studies suggest that SEPP1 is associated with poor prognosis as it promotes neovascularization and tumor invasion. This subtype was highly expressed in brain metastasis (40%) and lung cancer (45%), but rare in normal samples (4%). In the SEPP1_macro subtype, brain metastasis samples were enriched in signaling pathways such as tumor necrosis factor, PI3K-AKT, NF-kB, and Mitogen-activated protein kinase (MAPK), focusing mainly on the interaction of cytokines and cytokine receptors. Conclusions: In lung cancer and lung cancer brain metastasis, there is a significant presence of macrophages that promote angiogenesis and subpopulations of tumor-promoting cells associated with poor prognosis. The existence of these two cell subsets may indicate their activation during tumor metastasis and their regulatory role in the formation of new blood vessels, thereby promoting tumor growth.
Interchangeability of anti-PD1 antibodies in patients (pts) with metastatic NSCLC.
Authors: Kravchuk Darya , Fedyanin Mikhail , Ivan Borovkov , Moiseenko Fedor Vladimirovich , Zhukova Lyudmila , Pokataev Ilya , Rays Anastasia , Chubenko Viacheslav , Volkov Nikita , Ivanilov Kirill , Glazkova Elena
Published: July 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.
Current status of PD-(L)1 inhibitor usage in advanced or metastatic non-small cell lung cancer: A national survey of oncologists in China.
Authors: Wang Baocheng , Zhou Caicun , Wang Jun , Hu Jie , Duan Jianchun , Yao Yu , Li Guohui , Fan Yun , Huang Cheng , Chu Qian , Liu Chunling , Liu Lihua , Ma Zhiyong , Pan Yueyin , Su ChunXia , Shu Yongqian , Wang Yongsheng , Zhou Chengzhi , Zhao Mingfang , Zhang Xiaotao
Published: July 2024

e20559

Background: The aim of the present study conducted by Chinese Society of Clinical Oncology Expert Committee on Immunotherapy was to obtain real-world information on the use of PD-(L)1 inhibitors for non-small cell lung cancer (NSCLC) in different regions of China via a national questionnaire survey for oncologists. Methods: This survey was distributed online to cancer-related medical departments in 202 first-tier to fourth-tier cities of China between March to April 2023. The national survey consisted of four sections regarding oncologists’ concerns about immunotherapy as follows: treatment choice, response assessment, treatment duration, and management of immune-related adverse events (irAEs). Results: A total of 2,018 oncologists completed this survey. For advanced squamous (SQ) and non-squamous (NSQ) NSCLC without targetable genetic alterations, PD-(L)1 inhibitor-based regimens were the most widely used first-line treatment regimen (SQ: 52%, NSQ: 46%), followed by chemotherapy alone (SQ: 37%, NSQ: 37%) and other regimens (SQ: 11%, NSQ: 17%). The average treatment duration of 1L PD-(L)1 inhibitor-based regimens in SQ NSCLC and NSQ NSCLC were 6.4 and 6.2 cycles, respectively. 67% of oncologists may discontinue immunotherapy or change regimens when the first radiographic tumor assessment was SD per RECIST 1.1. Other reasons for early discontinuation of PD-(L)1 inhibitors before PD or unacceptable toxicity included economic reasons (78%) and patients’ low willingness to continue immunotherapy even they reached CR/PR (62%). Oncologists in the second-tier cities and below were more likely to discontinue immunotherapy when the tumors were stable, with shorter treatment duration of 5.7 cycles versus 7.1 cycles in the first-tier cities. The most common irAEs included dermatologic, endocrine, pulmonary, gastrointestinal, and hepatic toxicities. Conclusions: PD-(L)1 inhibitor-based regimens have become the priority choice for advanced NSCLC in China, however, the status of standardized continuous use of immunotherapy is obviously insufficient. There is a gap between clinical practice and clinical trials regarding PD-(L)1 inhibitor usage, which need more attention. [Table: see text]
Impact of race and gender on outcomes from patients with stage IV non-small cell lung cancer receiving immunotherapy: A retrospective study performed at Mitchell Cancer Institute, Mobile, AL.
Authors: Escobar Daisy E. , Muthyala Krithika , Ashfaq Muhammmad Areeb , Persing Brian Edward , Mulekar Madhuri S. , Prodduturvar Pranitha
Published: July 2024

e20562

Background: The use of immunotherapy is associated with improved survival among patients with Non-Small Cell Lung Cancer (NSCLC). The impact of race and gender on survival with immunotherapy is limited and conflicting. Our study sought to examine the influence of race and gender on the outcomes of patients with stage IV NSCLC treated with first line immunotherapy. Methods: A retrospective review of 91 patients with stage IV NSCLC was performed. Patients with confirmed NSCLC who received first line immunotherapy between January 2018 to December 2022 identified from Mitchell Cancer Institute (MCI) Cancer Registry were analyzed for clinical outcomes. Disease-specific survival was evaluated and compared among patients across racial/ethnic categories using mean, standard deviation, median, and interquartile range. Mean outcomes for numerical factors were compared using a t-test, while median outcomes were compared using a median test. The association between categorical factors was assessed using Fisher’s test, with a significance level of 0.05. Results: A total of 91 patients (45 [49.5%] male) were included in the analysis, with 61 White (67.0%; mean [SD] age, 70.2 [10.1] years) and 30 African American [AA] (32.9%; mean [SD] age, 65.9 [9.2] years). Based on histological analysis 71(77.8%) were adenocarcinoma, 18 (19.8%) squamous cell carcinoma, and 2 (2.2%) adenosquamous carcinoma. Mean progression free survival (PFS) was greater in Whites (315 vs 178 days; p = 0.041). Mean overall survival (OS) was longest in Whites (397 vs 218 days; p = 0.016). No significant differences were observed in age at diagnosis (p = 0.096), mean cycles given (p = 0.406) and PD-L1 status (p = 0.077) between Whites and AA’s. No significant differences were observed in age at diagnosis (p = 0.184), mean cycles given (p = 0.729) and time to progression (p = 0.769) or death (p = 0.938) between genders. PD-L1 distribution differed between males and females (p = 0.021) with a higher percentage of females having PD-L1 ≥1% (63% vs 38%). Conclusions: Our study showed longer PFS and OS in White patients receiving first line immunotherapy in stage IV NSCLC regardless of age at diagnosis or PD-L1 status. No differences in PFS or OS were seen between genders irrespective of age at diagnosis, mean cycles of treatment or PD-L1 status. These findings demonstrate the importance of integrating race, ethnicity, and gender as prognostic variables in the evaluation of patients with NSCLC in the incorporation of social determinants of health. This inclusion is crucial to obtain a more comprehensive understanding of how these factors influence patient outcomes.
First- and second-line biomarker utilization in non-small cell lung cancer.
Authors: Leong Matthew , Azimpouran Mahzad , McCloskey Audrey , Sankar Kamya , Vail Eric
Published: July 2024

e20564

Background: Targeted therapy has revolutionized the treatment of non-small cell lung cancer (NSCLC) since FDA-approval of the first EGFR-inhibitor in 2003. While number of actionable mutations and FDA-approved therapies has drastically increased, numerous studies have reported lackluster utilization rate of these therapies. Many of these studies take place in the community setting and focus on first line targeted therapy utilization. We aim to investigate the utilization rate of targeted therapies in an academic center, as well as explore utilization rate of newer second line therapies. Methods: The pathology database was queried for all stages of NSCLC cases with molecular testing (including qPCR, FISH, and NGS) from Jan 2016-Jan 2024. Patients with actionable alterations in EGFR, ALK, ROS1, BRAF, MET, RET, NTRK, KRAS, and ERBB2 ( HER2) that were detected six months prior to the first FDA approval for their respective targeted therapy were included. Patients who were lost to follow-up, those with early-stage non-metastatic tumors, or without progression on first line therapy at time of data cutoff (for actionable mutations with approved targeted second-line treatment) were subsequently excluded. Therapy plans and clinical course for the remaining patients were reviewed. Results: 355 NSCLC patients with actionable mutations were identified (210 EGFR, 63 ALK, 15 BRAF, 18 ROS1, 6 RET, 26 MET, 1 NTRK, 17 KRAS, 0 ERBB2). The following patients received an FDA-approved targeted first line therapy: EGFR (non-exon 20 insertion) 194/207 (94%), BRAF 8/15 (53%), ALK 60/63 (95%), ROS116/18 (89%), RET 5/6 (83%), MET 22/26 (85%), and NTRK 1/1 (100%). For FDA-approved second line therapy, KRAS 10/17 (59%) and EGFR (exon20 insertion) 2/3 (67%) patients received targeted therapy. No ERBB2 patients progressed. There was statistically significant difference between treatment rates between BRAF and non- BRAF first line therapies (p < .0002) and between rates of treatment with first and second line therapies (p < .0002). For those that did not receive eligible therapy, 15/37 (41%) received chemotherapy or immunotherapy treatment and 20/37 (54%) were too clinically severe for treatment. Conclusions: Despite most eligible patients receiving the appropriate targeted therapy (89%), there remains distinct subsets with significantly lower treatment rates. In particular, there is a large gap in treatment between the FDA-approved first and second line therapies as well as patients with BRAF mutations compared to other first line therapies. While the overall treatment rate based on molecular findings are higher than those reported from community settings, there remains patient populations which seemingly have their molecular findings overlooked. [Table: see text]
A single-arm phase II study of platinum doublet induction chemotherapy combined with toripalimab for driver gene-negative advanced NSCLC.
Authors: Lin Jinghui , He Zhiyong , Li Meifang , Chen Shijie , Weng Lihong
Published: July 2024

e20565

Background: PD-1/PD-L1 inhibitors combined with platinum doublet chemotherapy have become the standard first-line treatment for driver gene-negative advanced non-small cell lung cancer (NSCLC). However, not all patients can benefit from this treatment. Previous studies have shown that induction chemotherapy can reduce tumor burden, induce tumor immunogenic cell death, and improve the tumor immune microenvironment. Therefore, effective induction chemotherapy may enhance the efficacy of PD-1/PD-L1 immunotherapy. This single-arm, phase II clinical trial aims to evaluate the efficacy and safety of induction chemotherapy followed by immunotherapy (Toripalimab: PD-1 inhibitor) in treatment of driver gene-negative advanced NSCLC. Methods: Eligible patients received platinum doublet chemotherapy for 2-4 cycles (pemetrexed + platinum for adenocarcinoma; paclitaxel or gemcitabine + platinum for squamous cell carcinoma). patients who achieved tumor response (CR/PR/SD) received Toripalimab (240mg Q3W) for 2 years or until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS), which was defined as the duration from the initiation of induced chemotherapy to either tumor progression or death from any cause,and the secondary endpoints were toxicity, overall survival (OS), and clinical tumor response including objective response (defined as complete [CR] or partial response [PR]) and disease control (defined as CR, PR, or stable disease [SD]) during the course of combination treatment with Toripalimab following induction chemotherapy. Results: During the period from February 2020 through October 2023, a total of 19 qualified patients were enrolled in the study. As of December 31. 2023,the median follow-up was 22,9 months (range,15.9 to 30 months).11 patients (57.9%) experienced PFS events and 7 (36.8%) died, mOS were not reached. mPFS was 7.9 mo (95% CI,4.8-15.0months).12-month and 18-month PFS rate were 43% and 35%, respectively. One patient has not received tumor response assessment. Among the remaining 18 pts, 10 patients had a PR,5 patients had SD, and 3 patients had PD. The ORR and DCR were 55.6% and 83.3% respectively.42.1% (8/19) pts experienced immune-related adverse events(irAEs), included immune-related pneumonia (21.1%), rash (10.5%), hypothyroidism (10.5%). 2 pts experienced ≥3 grade irAEs, including grade 3 rash and grade 4 immune-related thrombocytopenia. Conclusions: Induction chemotherapy combined with Toripalimab achieved impressive 12-month and 18-month PFS rates in pts with driver gene-negative advanced NSCLC, along with manageable toxicities. These findings demonstrate the potential of induction chemotherapy could enhance the efficacy of immunotherapy. Clinical trial information: NCT04613804 .
Analysis of thromboembolic events in patients with non-small cell lung cancer treated with immune checkpoint inhibitors: A single-center real-world study.
Authors: Kim Tae-Hwan , Yang Cheongin , Choi Yong Won , Kwon Minsuk , Lee Hyun Woo , Kang Seok Yun , Ahn Mi Sun , Choi Jin-Hyuk
Published: July 2024

e20580

Background: Thromboembolic events (TEEs) are serious complications leading to significant morbidities and mortality in cancer patients (pts). Although incidences of 7-17% for TEEs were reported in non-small cell lung cancer (NSCLC) pts undergoing palliative chemotherapy, there were few reports on TEEs in NSCLC pts receiving immune checkpoint inhibitor (ICI) monotherapy. Methods: This study retrospectively analyzed 232 pts with stage III/IV or recurrent NSCLC who initiated palliative ICI monotherapy (1st line: 52, ≥2nd line: 180) from September 2017 to August 2022 in a single center. TEE occurrences were confirmed in pts during ICI treatment or within 6 months post-completion, while TEEs after regimen change were excluded. Results: Pembrolizumab (107 pts) was the most frequently administered agent, followed by atezolizumab (63 pts) and nivolumab (62 pts). TEEs were identified in a total of 14 pts (6.0%), and pulmonary thromboembolism was the most common type of TEEs (7 pts). No significant risk factors associated with TEE occurrence were identified, including age, performance status, Khorana score, type of drugs, and the line of chemotherapy. Conclusions: TEEs occurred at a relatively lower incidence in NSCLC pts receiving ICI monotherapy compared to previous studies involving cytotoxic chemotherapy, particularly platinum-based regimens. Nevertheless, the incidence is non-negligible and careful monitoring for TEEs in NSCLC pts undergoing ICI monotherapy is needed.
Real-world outcomes of osimertinib in Peruvian patients with advanced NSCLC with EGFR T790M-positive: A multi-institutional experience.
Authors: Galvez-Nino Marco , Roque Katia , Namuche Fernando , Ruiz Rossana , Paitan Amaro Victor , Coello Roberto , Cabrera Maria del Pilar , Maco Lorenzo , Ezquerra Juan Carlos , Perez Roca Rodolfo , Coanqui Ofelia , Valdivieso Natalia , Olivera Hurtado de Mendoza Mivael , Aguilar Cartagena Alfredo , Mas Luis
Published: July 2024

e20605

Background: Osimertinib is the standard of care for advanced NSCLC patients with EGFR T790M-positive whose disease has progressed to EGFR TKI therapy, however, the knowledge on the real benefit of these therapies in the Latin American setting remains unclear due the lack of access in the most countries. The aim of this study is to evaluate the outcomes of Osimertinib as sencond line treatment of advanced NSCLC patients with EGFR T790M-positive in a real-world Peruvian setting. Methods: This is a retrospective study of advanced NSCLC patients with EGFR T790M-positive treated with osimertinib at seven Peruvian institutions between July 2018 and May 2023. Outcomes were objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and OS from the start of first-line treatment to death. Results: We analyzed 41 T790M-positive patients with a median age of 60 years (range 36-87y), most of them were females (65.9%), 17.1% had smoking history and 19.5% biomass exposition as a main risk factor. About diagnosis and clinical features, T790M mutation was detected by liquid biopsy in 29.3% of cases, 36 patients (87.8%) had status performance 0 - 1 (ECOG) and 10 (24.4%) presented brain metastases as progression to the previous line of treatment. About outcomes, the ORR was 70.8%; with a median follow-up of 36 months, the median PFS was 15.2 months (95% IC, 9.6 - 20.7) and median OS since the start osimertinib was 16.3 months (95% IC, 7.6 - 24.9), no differences were found regarding the presence of brain metastases (p = 0.06 and p = 0.32) or type of mutation (p = 0.27 and p = 0.46) in both PFS and OS. Median OS from the start of first-line treatment was 46.6 months (95% IC, 34.5 - 58.7). As supplementary analysis, in the same period of time, 11 T790M-positive patients who did not receive osimertinib as second line of treatment achieved a median OS from the start of first-line treatment of 23.5 months (95% IC, 16.5 - 30.5). This OS was significantly lower compared to those who did receive osimertinib (p = 0.001). Conclusions: This study confirms the efficacy of osimertinib in the real world when used as a second line of treatment in T790M-positive patients, in addition the feasibility of osimertinib in this setting may significantly impact the survival.
Time-to-treatment for metastatic non-small cell lung cancer in the era of biomarker testing.
Authors: Akanbi Maxwell Oluwole , Kenmoe Jerry , Adekolujo Samuel O , Saleem Muhammad , Koduru Ujwala , Hrinczenko Borys
Published: July 2024

e20623

Background: In 2011, the National Comprehensive Cancer Network (NCCN) recommended biomarker testing in patients with metastatic non-small cell lung cancer (mNSCLC) based on improved survival with targeted therapies and immunotherapy reported in clinical trials. The requirement for biomarker testing before the commencement of treatment could inadvertently contribute to delays in treatment initiation. We investigated the time to treatment for mNSCLC in the US general population in the era of advanced therapies for lung cancer. Methods: We obtained data from 32,518 adults with mNSCLC between 2004 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database. We categorized time to treatment to < 1 month or ≥ 1 month, and period of diagnosis to 2004-2011 and 2012-2020. We used separate logistic regression models to investigate the relationship between time to treatment, period of diagnosis, and year of diagnosis, adjusting for age, sex, household income, residence, and race. Results: The mean age of the study population was 66 (SD 10) years, 41% Female and 76% White. The majority (84%) were Metropolitan dwellers. A total of 23,322 (76%) were diagnosed between 2004 and 2011, and 9,186 (28%) from 2012 to 2019. Overall, 40% of patients initiated cancer therapy within a month of diagnosis, with no significant difference between patients who commenced treatment between 2004-2011 (40.2%) and 2012-2019 (39.9) (chi2 = 0.3492 P = 0.555). In both logistic regression analyses, there was no significant relationship between time to treatment and period or year of diagnosis. However, race/ethnicity and age independently predicted the time to treatment. Compared to Whites, Blacks (Odds ratio (OR) 1.08, 95% CI 1.01- 1.16, p = 0.04) and Hispanics (OR 1.26, 95% CI 1.03-1.24, p 0.01) were more likely to initiate treatment ≥ 1 month from the time of diagnosis. The odds of initiating treatment ≥ 1 month also increased with age (Age/year OR 1.01 (95% CI 1.01-1.01). Conclusions: We did not identify delays in treatment initiation for mNSCLC in the current era of biomarker testing. Biomarker testing has become an essential diagnostic tool for mNSCLC, guiding targeted therapies that have been shown to improve treatment outcomes. However, some vulnerable populations continue to experience delays in treatment initiation, which could lead to poorer survival. Improvements in cancer therapeutics must be complemented by service delivery improvements to optimize treatment outcomes.
Assessing clinician familiarity with integrative oncology and uptake of an electronic medical record–based education resource.
Authors: Jiang Joshua , Gonzales Nikko , Anand Sidharth
Published: July 2024

e21001

Background: Integrative oncology is the practice of incorporating complementary and alternative medicine (CAM) into the conventional care of cancer. CAM encompasses a broad realm of treatment modalities, ranging from nutrition and exercise to acupuncture, supplements, and behavioral therapy. Few oncologists discuss CAM with their patients while patients under-report their usage of these treatments to their oncologists. Our project aim was to assess clinician familiarity with integrative oncology and to improve education on the topic using a clinician-facing tool accessible through the electronic medical record (EMR). Methods: We distributed a survey from May through July 2023 to assess attitudes towards CAM and practice patterns at an academic oncology department. Respondents used a five-point Likert scale to rate their understanding of CAM, role in counseling patients on CAM, and factors affecting their discussion of such topics. We created EMR-accessible clinician guides which reviewed the evidence base for common complementary treatments in breast, colon, and lung cancer. Results: Fifteen of 64 (23%) affiliated oncologists completed the survey. Eleven (73%) respondents agreed or strongly agreed that it is their responsibility to learn about CAM. Fourteen (93%) respondents agreed or strongly agreed that it is their responsibility to ask patients about CAM usage, although two-thirds of respondents initiated conversations about CAM “sometimes” or less. Six (40%) felt comfortable providing resources on CAM to their patients. Respondents reported greatest awareness of the evidence for exercise and psychotherapy (average rating 3.8 out of 5; higher is more familiar) and least awareness for supplements (average 3.2). The factors most strongly affecting respondents’ practices of discussing CAM with patients were a lack of credible resources and fear that supplements might replace conventional cancer treatment. Ten (67%) respondents reported that patients undergoing active treatment often or always ask about CAM and nine (60%) reported that survivors often or always ask about CAM. Three practicing oncologists and two fellows had added our clinical guides to their EMR shortcuts six months after their introduction. Conclusions: Certain forms of CAM remain controversial within oncology practice. Although oncologists in our department reported a sense of responsibility to understand and counsel patients on CAM, multiple barriers impeded physician comfort with the topic and uptake of a novel educational resource was limited. Patients undergoing active treatment and survivors alike asked clinicians about CAM, which suggests it is an important area of competence for oncologists regardless of treatment phase.