bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality metrics analysis in patients who received Lutetium-177 PSMA-617 (177Lu–PSMA) therapy in a real-world practice setting.
Authors: Yazdanpanah Omid , Dwabe Sami , Warnecke Brian , Benjamin David Joseph , Srinivas Shyam M. , Rezazadeh Arash , Mar Nataliya
Published: July 2024

e17049

Background: 177Lu–PSMA is a radiolabeled small molecule that delivers β radiation to cells expressing prostate-specific membrane antigen (PSMA). It has been approved for use in metastatic castration-resistant prostate cancer (mCPRC) in 3/2022, based on VISION study. The Food and Drug Administration (FDA) label for 177Lu–PSMA requires prior therapy with an androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy as well as presence of at least one PSMA-positive tumor with uptake greater than normal liver and no PSMA-negative lesions on a PSMA positron emission tomography (PET) scan. In the VISION study, PSMA PET was performed within 4 weeks of therapy start. Further, patient received either 177Lu–PSMA plus protocol permitted standard of care (SOC), including ARPI, or SOC alone. Given the relatively recent approval of this therapy, real-world familiarity with administration of this agent may not be optimal. Methods: A retrospective analysis of 25 patients with mCRPC who received 177Lu–PSMA therapy since 3/2022 at the University of California Irvine (24/25) and Hoag Hospital (1/25) was performed. Multiple variables were analyzed and compared to the FDA label for this agent as well as design of the VISION study. Results: All patients in this study had received an ARPI and at least one taxane chemotherapy prior to 177Lu–PSMA. A PSMA-PET scan was obtained prior to 177Lu–PSMA therapy in all patients. The timing of the scan was within 4 weeks of starting 177Lu–PSMA therapy in only 5/25 (20.0%) patients. The average time from PSMA PET scan to 177Lu–PSMA therapy start was 66 days [range: 18 - 326 days]. None of the PSMA PET scan reports included a baseline liver standardized uptake value (SUV) or mentioned whether any lesions were non PSMA-avid. All reports provided SUV values for some, but not all, PSMA-avid lesions. The average maximum SUV of the most PSMA-avid lesion noted on the reports was 34.7. All PSMA PET scans were retrospectively reviewed by a nuclear medicine specialist and the average maximum SUV of the most PSMA-avid lesion on re-review was 42.0 (p <0.05). During 177Lu–PSMA therapy, co-administration of ARPI occurred in 10/24 (23.8%) of patients. Conclusions: This study highlights the differences in quality metrics between patients who received 177Lu–PSMA therapy in a real-world practice setting compared to the FDA label for this agent and VISION study design. Differences included lack of uniform PSMA PET scan reporting, timing of obtaining pre-treatment PSMA PET imaging, and co-administration of ARPI. Development of institutional algorithms around administration of 177Lu–PSMA therapy may be needed.
Urinary-based detection of MSL, HE4, and CA125 as an additional dimension for predictive and prognostic modelling in ovarian cancer.
Authors: Wimberger Pauline , Schwarz Franziska Maria , Klotz Daniel , Kuhlmann Jan Dominik
Published: July 2024

e17567

Background: We have recently described a predictive/prognostic model for ovarian cancer, exploiting commonly available clinico-pathological parameters and the ovarian serum biomarkers mesothelin (MSL), human epididymis protein 4 (HE4) and cancer-antigen 125 (CA125). Considering urine as a prototype non-invasive sample, we investigated whether serum levels of these biomarkers are mirrored in urine and compared their clinical relevance in matched serum vs. urine samples. Methods: MSL, HE4 and CA125 were quantified by Lumipulse G chemiluminescent enzyme immunoassay (Fujirebio). In total, this study was based on 1080 biomarker detection runs from 188 serum and 172 urine samples from 192 ovarian cancer patients. Results: While absolute concentrations of MSL and CA125 were higher in serum than in urine, serum HE4 concentrations were considerably lower than urinary HE4 concentrations. Nonetheless, relative intra-patient levels of all three biomarkers strongly correlated between matched serum vs. urinary samples and were unrelated to BRCA1/2 mutational status. Consequently, prediction of surgical outcome or relapse/death by MSL, HE4 or CA125 was similarly efficient among urinary- vs. serum-based detection. HE4 provided the highest capacity in predicting surgical outcome and relapse/death among both body fluid types (urinary HE4: AUC=0.854; AUC=0.750, respectively). All clinically relevant findings of urinary MSL, HE4 and CA125 were reproducible among raw vs. creatinine-normalized datasets, suggesting that normalization may have subordinate priority for urine-based analysis. Conclusions: We report that the capacity of MSL, HE4 and CA125 for predicting surgical outcome and relapse/death is equivalent between serum vs. urine-based detection. Urinary biomarkers, in particular HE4, may provide an additional dimension for prognostic modeling in ovarian cancer.
Ovarian-Adnexal Reporting & Data System (O-RADS) versus modified benign descriptors and IOTA ADNEX (two-step strategy) in classification of ovarian masses.
Authors: Rodríguez Nadiezhda , Pérez Sophia , Rodríguez Juan Nicolás , Cantor Nicolás , Ardila Fabian , Esquivel Alba Liliana , Segovia Javier
Published: July 2024

e17569

Background: The use of a single and common language in the diagnosis of ovarian tumors is a multidisciplinary effort spanning several decades that has allowed the global adoption of the Ovarian-Adnexal Reporting & Data System (O-RADS) and the International Ovarian Tumor Analysis (IOTA). The objective is to determine the diagnostic accuracy of O-RADS versus modified benign descriptors and IOTA ADNEX in the classification of adnexal masses. Methods: Ambispective diagnostic accuracy study based on ultrasound data collected at a university hospital with a gynecologic oncology unit between 2012 and 2022. Two IOTA-certified level III sonographers classified adnexal masses using modified benign descriptors (MBD). The main outcome was the classification of the masses as benign or malignant for each strategy. Histopathology was used as the diagnostic reference standard. A diagnostic test analysis was performed. Results: 876 patients with 902 adnexal masses were included in the study for both analysis strategies. For the two-step analysis, 573 (64%) met the classification criteria for their evaluation based on MBD (first step) and 329 (36%) were assessed using IOTA ADNEX. 99% (567/573) of the masses classified according to the MBD, were benign by histopathology. The diagnostic performance of IOTA ADNEX (second step) had a sensibility of 93%, specificity of 64%, positive predictive value of 48%, negative predictive value of 96%, AUC (0,880). Regarding the analysis of the O-RADS system to stratify malignancy risk, we observed a prevalence of 58% for O-RADS 2, 22% for O-RADS 3, 11% for O-RADS 4, and 9% for O-RADS 5. Sensibility was 92%, specificity 88%, positive predictive value 48%, negative predictive value del 99%, AUC (0,886). Conclusions: In our experience, the diagnostic accuracy of the two-step strategy or the O-RADS system is similar. However, the ORADS system had a lower proportion of false negatives.
Outcomes in STK11-, KEAP1-, and KRAS-mutant lung squamous cell carcinoma (LSCC) with use of immune checkpoint inhibitors (ICIs).
Authors: Marin-Acevedo Julian A. A. , Shi Justin Wang , Han Yan , Tran Mya , Karkash Ahmad , He Weston , Shields Misty Dawn , Hanna Nasser H.
Published: July 2024

e20504

Background: Studies have suggested that STK11, KEAP1, and KRAS mutations impact response to ICIs in individuals with lung adenocarcinoma. The effect of these mutations in LSCC is unknown. Methods: We conducted a retrospective analysis from January 1, 2018 through December 31, 2023 evaluating individuals seen in the Indiana University Health System with STK11, KEAP1, or KRAS-mutant advanced LSCC treated with ICI-based therapy. Demographic information and baseline PD-L1 levels were collected. Response to therapy was assessed using standardized real-world criteria. Progression-free survival (PFS) was calculated using the Kaplan-Meier method and compared using a log-rank test. Results: Thirty-one of 316 evaluable patients with LSCC had a mutation in KEAP1, STK11, or KRAS. Twenty-one of those individuals had advanced disease treated with ICIs. Nine of 21 had tumors harboring KEAP1 and/or STK11, 10 had tumors harboring KRAS, and 2 had KRAS + STK11-mutant tumors. The median age was 67 years, 71% (15/21) were male, 86% (18/21) were White, 83% (15/18) had PD-L1 levels ≥1%, and 81% (17/21) were evaluable for response including 11 treated with ICIs + chemotherapy and 6 who received ICIs alone. The overall response rate (ORR) was 65% with 5 individuals having progressive disease (PD), 1 with stable disease (SD), and 11 exhibiting partial response (PR). Those receiving ICIs + chemotherapy had an ORR of 73% (3 PD, 8 PR). The ORR was 50% (2 PD, 1 SD, 3 PR) in the cohort treated with ICIs alone. Among those with KEAP1 and/or STK11 mutations, the ORR was 43% (4 PD, 3 PR). The ORR was 88% for the KRAS-mutant cohort (1 SD, 7 PR) and 50% in the KRAS + STK11 subgroup (1 PD, 1PR). The median PFS was 6.4 months for the entire population, 6.0 months for those treated with ICIs + chemotherapy, and 8.1 months for those receiving ICIs alone. Although the cohort size was limited, individuals with KRAS mutations appeared to have improved PFS compared to those with STK11, KEAP1, or KRAS + STK11 mutations treated with ICI-based therapy (Table 1). Conclusions: STK11, KEAP1, and KRAS mutations impact response to ICIs in individuals with LSCC. There was a trend toward improved ORR and PFS in those with KRAS-mutant LSCC treated with ICI-based therapy compared to those with STK11, KEAP1, or KRAS + STK11-mutations. [Table: see text]
Impact of intratumor heterogeneity (ITH) on survival outcomes in patients with non-small cell lung cancer (NSCLC) with high tumor mutational burden (TMB-H).
Authors: Fridland Stanislav , Kim Hye Sung , Chae Young Kwang
Published: July 2024

e20519

Background: Heterogeneity among cancer cells within a tumor significantly impacts cancer development and resistance to treatment. Currently, no standard measure exists for assessing ITH in routine clinical settings. In this study, we applied a quantitative metric to assess intratumor genetic diversity in NSCLC, using a large, multicenter database. Methods: We accessed the Tempus database for next-generation sequencing results from patients with NSCLC who underwent immune checkpoint inhibitor (ICIs) monotherapy as their first-line treatment. We calculated the mutant-allele tumor heterogeneity (MATH), defined as the ratio of the distribution's range to the median of mutant-allele fractions across tumor-specific mutated loci. The primary outcomes were progression-free survival (PFS) and overall survival (OS). Results: A total of 160 pembrolizumab Significant differences in PFS between high and low MATH groups (MATH-H and MATH-L, respectively), using the 50th percentile as the cutoff, were observed among patients with stage 4 adenocarcinoma who had TMB-H above the 25th percentile (Table). In this subgroup, with 27 patients in the MATH-H/TMB-H group and 22 in the MATH-L/TMB-H group, the MATH-H/TMB-H group showed improved PFS (median PFS 5.19 vs. 1.61 months; p = 0.02). Differences in PFS were also observed among patients with TP53, KEAP1, and MET mutations (p < 0.001, p = 0.02, and p = 0.004, respectively). TP53 mutations were found in 27.6% of the MATH-H group and 27.8% of the MATH-L group, KEAP1 mutations in 8.2% and 10.1%, respectively, and MET mutations in 5.1% and 8.9%, respectively. No significant PFS differences were found in groups with low TMB, other stages, or squamous histology. Conclusions: Our findings suggest that higher genetic diversity within stage 4 TMB-H lung adenocarcinoma, as quantified by MATH, might be linked to improved clinical outcomes among those who receive pembrolizumab as first-line therapy and supports further exploration of MATH as a predictive/prognostic biomarker. [Table: see text]
Health outcomes of pembrolizumab plus chemotherapy in non-small cell lung cancer.
Authors: Marin Pozo Juan Francisco , Cao Viña Vanesa , Plaza Arbeo Ainoa , Morales Rivero Begoña , Ortega Granados Ana Laura , Lopez Lopez Jose Antonio
Published: July 2024

e20527

Background: Pembrolizumab (PEM) is a standard of treatment for advanced or metastatic non-small cell lung cancer (m-nSCLC) in tumors without biomarker actionable. The clinical practice protocol for m-nSCLC in our hospital includes PEM monotherapy if PD-L1 ≥50% and PEM+chemotherapy (PEM+CT) if PD-L1 1-49% or negative. The aim of this study is to determine the effectiveness results of PEM+CT in m-nSCLC in real clinical practice. Methods: It was designed a single center, observational and retrospective study. We included all patients (pts) treated with PEM+CT as first line of therapy with m-nSCLC of September-2019 to August-2023 at a hospital from south Spain, cut-off date 11/30/2023. The primary endpoints were overall survival (OS) and progression-free survival (PFS). The results were analyzed for population and by subgroups (histology, ECOG, previous localized disease (LD) and other), using Kaplan-Meier method. Results: 103 pts were enrolled (89% men), mean age was 66.2 years, 48.5% of pts had ECOG 0, 40.8% ECOG 1 and the rest ECOG 2-3. The tumors were 64.1 % non-squamous histology. 28.2% pts were treated for previous localized disease and 39.8% pts received radiation therapy at some point during treatment. At start of therapy the mean WBC count with PEM+CT was 10.0 x10(9)/L (sd=6.2). With a median follow-up of 10.8 months (m) the median for treatment duration was 5.7 m [95%CI 4.3-7.2].PFS was 7.2 m [IC95% 5.9-8.6] for all pts, 6.6 m [IC95% 4.6-8.7] for non-squamous and 8.2 m [IC95% 4.6-11.7] for squamous histology, p=0.158. OS was 14.2 m [IC95% 10.2-18.2] for all pts, 13.1 m [IC95% 7.6-18.6] and 14.2 [IC95% 9.3-19.2] by non-squamous and squamous histology, respectively, p=0.396.We found statistically significant difference in OS between: pts with ECOG 0-1 (median 15.1 m [IC95% 11.6-18.7]) vs pts with EOCG 2-3 (median 6.6 m [IC95% 1.6-11.6]), p=0.046 and pts previously treated pts of LD (median 21.7 m [IC95% 2.5-40.8]) vs pts with advanced or metastatic disease at onset (median 10.5 m [IC95% 5.2-15.9]), p=0.025. Another subgroup analysis is shown in table. Conclusions: The effectiveness of PEM+CT was similar in OS and PFS values to that of the pivotal trials. In contrast to these, our results were slightly better in squamous histology. The OS was better in pts with ECOG 0-1 and previously treated of localized disease, highlighting the importance of early diagnosis. [Table: see text]
Effect of first-line bevacizumab on prognosis of second or later-line immunotherapy in patients with advanced non-squamous non-small cell lung cancer: A retrospective analysis.
Authors: Chen Qian , Yuan Shumin , Liu Ni , Wang Huimin , Shang Xiaoling , Ma Xinchun , Sun Ying , Wei Chenxi , Liu Lian , Wang Xiuwen , Liu Yanguo
Published: July 2024

e20570

Background: Previous studies have demonstrated that anti-angiogenic agents have the capacity to regulate tumor microenvironment and may affect the clinical effect of immune checkpoint inhibitors (ICIs). However, the impact of previous anti-angiogenic agents on clinical outcomes of non-squamous non-small cell lung cancer (nsqNSCLC) patients treated with ICIs remains unclear. Methods: In the present study, we incorporated POPLAR, OAK, and BIRCH trials with a total of 912 non-squamous NSCLC patients. Using Vivli data-sharing platform, we have obtained specific clinical information about individual patients. The progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier analysis with a log-rank test, and the corresponding hazard ratio (HR) and 95% confidence interval (CI) were estimated using the Cox proportional regression model. Chi-squared test was used to compare proportions between different groups. All statistical analysis and plotting were done in R version 4.1.1 and SPSS R26.0.0.2. P less than 0.05 was considered statistically significant. Results: In the overall cohort, PFS (2.77 months vs. 2.83 months; hazard ratio [HR],1.1; 95% confidence interval [CI], 0.9 to 1.3; p = 0.43) and OS (15.1 months vs. 14.3 months; HR,1.0; 95% CI, 0.8 to 1.3; p = 0.86) in patients treated with bevacizumab before atezolizumab (pre-bevacizumab group) and patients treated without bevacizumab before atezolizumab (no pre-bevacizumab group) were not statistically different. Merely in patients with KRAS mutation, no pre-bevacizumab group had an improved PFS (4.04 months vs. 1.64 months; HR,1.7; 95% CI, 1.0 to 2.7; p = 0.04) as compared to the pre-bevacizumab group. Longer use of bevacizumab (≥1.43 months) before atezolizumab suggested a longer PFS compared with shorter use of bevacizumab ( < 1.43 months) (20.07 months vs. 2.75 months; HR,0.40; 95% CI, 0.17 to 0.95; p = 0.03). Conclusions: In conclusion, our study demonstrated that whether or not first-line bevacizumab is given has no effect on PFS or OS of second-line or later-line immunotherapies. Patients with longer duration of first-line bevacizumab use have a longer PFS on later immunotherapy. The more appropriate timing and sequence of administration of anti-angiogenic agents and ICIs will help us achieve a better therapeutic effect in the clinical practice of patients with advanced NSCLC.
Response to first-line therapies in metastatic lung adenocarcinoma with low PD-L1 expression: A multi-center retrospective study.
Authors: Ge Yihui , Gao Aiqin , Sun Yuping , Li Juan , Wang Shuyun , Wang Jian , Wei Xiaojuan , Wang Leirong , Cheng Qinglei , Wang Xiufen , Zhang Jian , Fu Xuebing
Published: July 2024

e20574

Background: For metastatic lung adenocarcinoma with low PD-L1 expression (tumor proportion score:1-49%), chemotherapy in combination with immune checkpoint inhibitors (IC), with bevacizumab (BC), or with both (IBC) have been established as standard first-line options. However, the optimal scheme is still undetermined. Methods: This retrospective study enrolled 125 metastatic lung adenocarcinoma patients with low PD-L1 expression from four cancer centers. All the patients received IC, BC, or IBC as the first-line therapies. Propensity score matching (PSM) with a ratio of 1:1:1 was used to balance the inter-group clinical characteristics. Efficacy, including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS), as well as safety were evaluated. Results: 35 of the 125 patients received IBC, 37 received BC, and 53 received IC. After PSM, a total of 35 pairs of patients were enrolled in the analysis. Patients receiving IBC (ORR: 57.1%, DCR:100%) or IC (ORR: 57.1%, DCR: 91.4%) obtained superior ORR and DCR in relative to those receiving BC (ORR: 45.7%, DCR: 82.9%). However, only IBC (median PFS: 20.47m; median OS: not research) rather than IC (median PFS: 10.0m; median OS: 21.36m) treatment generated significantly prolonged PFS and OS compared with BC (median PFS: 9.43m, P = 0.007; median OS: 23.2m, P = 0.048). We further analyzed the survival benefit based on different clinical and molecular features. We found patients with female gender had more significant OS benefit from IBC treatment over IC or BC treatment. In addition, non-smokers benefit more from IBC compared with IC. The occurrence of adverse events (AEs) was more frequent in IBC (74.3%) and IC (85.7%) group in relative to BC group (42.8%). Meanwhile, ≥ grade 3 AEs (22.9%) was markedly higher in IBC group compared with that in BC group (5.7%). However, leukopenia and neutropenia represent the most common ≥ grade 3 AEs, which are easy to be clinically managed. Conclusions: For metastatic lung adenocarcinoma patients with low PD-L1 expression, IBC is the preferred first-line therapy in terms of survival. However, the AEs should be carefully concerned.
Real-world data analysis of first-line targeted therapy for patients with non-small cell lung cancer with different EGFR mutation status in a tertiary care hospital.
Authors: Peng Yang , Liao Ziyi
Published: July 2024

e20586

Background: Lung cancer is still the malignant tumor with the highest incidence and mortality rate in the world, of which non-small cell lung cancer (NSCLC) accounts for about 85%. The EGFR mutation rate in Asians is 30%-60%, with exon 19 deletion mutations and exon 21 L858R point mutations accounting for about 90% of EGFR mutations, which are the classic EGFR mutation types. The two have significant differences in clinical characteristics, and some clinical trials have shown differences in efficacy between different subgroups, but whether they exist in the real world needs to be further confirmed. Meanwhile, the efficacy of first-line targeted therapy in patients with coexisting mutant NSCLC harboring different EGFR classical mutations and whether there is a difference in different subgroups has not been conclusively determined. Methods: To collect general clinical data and their genetic test reports of NSCLC patients diagnosed with gene mutations who attended the Affiliated Hospital of North Sichuan Medical College from January 2019 to December 2021 for follow-up, with a follow-up date of June 30,2023, as the end date. Kaplan-Meier survival analysis and log-rank test were applied to compare:1)the median PFS in different subgroups of patients with no co-mutation classic EGFR mutation;2)the median PFS in patients with co-mutation classic EGRR mutation and no co-mutation classic EGFR mutation;3)the median PFS in different subgroups of patients with no co-mutation 19-Del/L858R and with co-mutation 19-Del/L858Rpatients;4)median PFS of patients between co-mutated 19-Del and L858R subgroups. Results: The median PFS of 19Del was significantly better than that of L858R in different subgroups of EGFR classical mutations (14.0 months vs. 8.1 months, p = 0.004 < 0.05). The median PFS of EGFR classical mutation was significantly better than that of EGFR classical mutation with co-mutation,11.1months vs. 5.8 months, respectively, p < 0.001. In different subgroups,19Del median PFS was superior to 19Del co-mutation (14.0 months vs. 6.1 months, p = 0.001 < 0.05),and L858R median PFS was superior to L858R co-mutation (8.1 months vs. 5.8 months, p = 0.449 > 0.05). 19Del co-mutation and L858R co-mutation median PFS were not observed in the analysis of the same simple 19del first-line targeted therapy survival benefit was significantly better than the similar survival benefit of L858R, whose median PFS was 6.1 months vs. 5.8 months, respectively, p = 0.449>0.05, the difference was not statistically significant. Conclusions: The survival benefit of first-line targeted therapy for 19Del in the real world is superior to that of L858R, while the clinical benefit of first-line targeted therapy is poor for classical mutations in EGFR with co-mutations, and combinations with other therapeutic modalities should be considered.
Prognostic factors for survival in NSCLC treated with immunotherapy: An institutional analysis.
Authors: Huang Judy , Khullar Rohit , Bhattacharya Moinak , Keresztes Roger , Prasanna Prateek , Sher Amna Falak
Published: July 2024

e20591

Background: Immune check point inhibitors (ICIs) are the cornerstone of treatment for patients with advanced NSCLC. However, not all patients benefit from ICIs and some develop significant immune-mediated toxicities. There is limited data regarding prognostic factors in NSCLC patients treated with ICIs. Imaging features can complement clinical variables in predicting response to ICIs. This study aims to evaluate CEA, blood leukocyte markers, and novel CT-derived radiomic features as factors predictive of survival in this patient population. Methods: In this retrospective study, clinical data from patients with advanced stage NSCLC treated with ICIs at Stony Brook University Hospital from 2016 to 2021 were collected. Baseline and subsequent CEA (carcinoembryonic antigen), ANC (absolute neutrophil count), ALC (absolute lymphocyte count), NLR (neutrophil to lymphocyte ratio), AEC (absolute eosinophil count), and AMC (absolute monocyte count) were evaluated as independent prognostic factors. 3-D segmentation of ipsilateral lung lobe was obtained using U-Net and radiologist report of tumor location. 600 stable IBSI-standardized features were extracted from the region using PyRadiomics. The discriminative ability of clinical and image-derived variables was assessed using Kaplan-Meier survival and Cox proportional hazards regression analysis. Results: This study included 80 patients. Objective response rate (ORR) was 25.0% with 1-year OS of 58.0%. PD-L1 expression ≥ 50% was significantly associated with survival (p < 0.02). Decrease in CEA (p < 0.01) and 5% increase in AEC (p = 0.027) significantly correlated with survival. Age, sex, clinical stage, ANC, ALC, NLR, AMC did not significantly predict survival. Three image biomarkers that correlated with median enhancement of tissue on chest CT, and degree of tissue heterogeneity were significant predictors of mortality (p < 0.02). A multivariable model with clinical inputs outperformed one with radiomic features only (C-index 0.70 vs. 0.64). Clinical and radiomic inputs together performed well in predicting survival (C-index 0.76). Conclusions: Changes in CEA and AEC were the strongest predictors of survival in advanced NSCLC patients treated with ICIs. This study suggests that combined clinical and radiomic biomarkers (quantifying local lobar heterogeneity) can identify patients most likely to benefit from immunotherapy. [Table: see text]
Real-world KRAS testing and treatment utilization among patients with metastatic non-small cell lung cancer.
Authors: Blanc Simon , Vasudevan Anupama , Gart Mike , Sura Teena , Shrivastava Aryamaan , Varughese Prateesh , Scott Jeffrey A.
Published: July 2024

e20593

Background: About 30% of patients with non-small cell lung cancer (NSCLC) have been reported to harbor gene mutations of Kirsten rat sarcoma oncogene homologue (KRAS). KRAS testing is recommended at metastatic NSCLC (mNSCLC) diagnosis and targeted treatment has shown better outcomes among KRAS-positive patients. This study aimed to understand KRAS testing rates among mNSCLC patients and utilization of targeted treatment among KRAS G12C positive patients treated in the community oncology setting. Methods: A random sample of 836 mNSCLC patients from the Integra Connect PrecisionQ de-identified database was included in this retrospective observational analysis, with additional information supplemented by chart curation. The database contains ~80% community oncology and ~20% academic practices with over 3 million cancer patients across 500 sites of care. Eligible patients were those aged ≥18 years, diagnosed with mNSCLC, and who initiated treatment in the second line (2L) setting between 01-May-2021 and 01-Jan-2024. KRAS testing rates and utilization of targeted treatment use were assessed and presented for this study. Results: The median (IQR) age of 836 mNSCLC patients was 68 (62,75) years; 52.9% were female; 73.8% identified as White, 11.7% as African American, 1.9% as Asian, and 12.6% as Other. Testing for KRAS was reported in 749 (89.6%) of the mNSCLC patients any time during the evaluation period, with most of them (738/749) tested before 2L treatment initiation; 186/749 (24.8%) of those patients were positive, and 74 were KRAS G12C positive. Of the KRAS G12C positive patients, 53/74 (71.6%) reported a targeted KRAS treatment in the 2L or greater setting. Conclusions: In this real-world setting, the testing rates for KRAS are almost 90%, with about 70% of the mutated patients receiving a targeted treatment. However, there is still a proportion of patients who did not receive KRAS testing or targeted treatment in this real-world setting. Appropriate and timely testing and utilization of the targeted treatment is necessary for better patient outcomes. [Table: see text]
Efficacy of systemic treatments in patients with metastatic lung invasive mucinous adenocarcinoma.
Authors: Demir Tarik , Araz Murat , Hendem Engin , Kocak Mehmet Zahid , Erman Mustafa , Bas Onur , Köstek Osman , Sever Nadiye , Zeynelgil Esra , Karakaya Serdar , Moloney Carolyn , Chung Liam IL-Young , Chae Young Kwang
Published: July 2024

e20609

Background: Invasive mucinous adenocarcinoma (IMA) is a relatively rare histological subtype of lung adenocarcinomas that differs in its clinical behavior, radiologic features, histopathological, and genomic characteristics than invasive non-mucinous adenocarcinomas (INMA). Methods: We retrospectively investigated medical records of patients diagnosed with lung IMA at four oncology centers in Turkey. Patients who were ≥18 years of age, pathologically diagnosed with lung IMA, and who received at least one course of treatment for metastatic or inoperable disease were included in the study. Results: Forty-one patients were included in the study. The median follow-up was 16.6 months. Among the included patients, 24 (58.5%) were male, 17 (38.5%) were female, and their average age was 62. Six (14.6%) patients had a targetable mutation. Three (7.3%) patients were epidermal growth factor receptor (EGFR), two (4.8%) anaplastic lymphoma kinase (ALK) mutation, and one (2.4%) neurotrophic tyrosine receptor kinase (NTRK2) fusion. Most patients (83.1%) had received platinum-based chemotherapy as a first-line treatment. Of the patients who received cytotoxic chemotherapy, 9 (25.7%) had a partial response, 14 (40%) had a stable response, and 12 (34.3%) had progression. The median PFS was 8.24 months (95% CI: 5.9-10.5 months), and the median OS was 20.4 months (95% CI: 14.4-26.3 months) in all study populations. In those receiving cytotoxic chemotherapy, median PFS and OS were 8.11 months (95% CI: 5.02-11.2) and 17.5 months (95% CI: 11.7-23.3 months), respectively. While the PFS of two EGFR-positive patients were similar at 18.9 months and 20.6 months, the third patient's PFS was quite prolonged (66.5 months). The ALK-positive patients receiving brigatinib and crizotinib PFS were 15.8 months and 2.73 months, respectively. The PFS of the patient receiving entrectinib was only two months. Among the entire patient population, only one patient used oxaliplatin and capecitabine combination (XELOX) as chemotherapy. In this patient, who progressed after four cycles of gemcitabine and platinum first-line treatment, a partial response and 7.23 months PFS were achieved with second line XELOX. Conclusions: Standard-of-care treatments have the same efficacy in IMA and INMA patients. Targetable mutation is less common in IMA patients compared to INMA. 5-FU-based chemotherapies also appear to be effective in lung IMA patients.
The patient outcomes with EGFR-mutated advanced non-small-cell lung cancer receiving aumolertinib as first-line treatment.
Authors: Li Jisheng , Zhao Wen , Li Hongxin , Xuan Tiantian , Wang Chengjun , Zhang Rongyu , Yang Chuang , Wang Jian , Yi Cuihua
Published: July 2024

e20619

Background: As a novel third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), aumolertinib demonstrated superior progression-free survival and a well-tolerated toxicity profile to gefitinib in front-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) in the AENEAS trial. However, the real-world impact of aumolertinib in the first-line treatment on patients' HRQoL still remains unclear. Methods: Advanced NSCLC patients with sensitizing EGFR mutations treated with aumolertinib 110 mg daily in the first-line treatment were prospectively enrolled and the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) and EORTC Quality of Life lung cancer-specific module (QLQ-LC13) information were collected. Efficacy evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 was also recorded here. Prespecified key symptoms were cough, hemoptysis, dyspnea, sore mouth or tongue, dysphagia, hair loss, tingling hands or feet, chest pain, arm or shoulder pain and pain of other sites. Results: Totally, 33 patients in the first-line treatment were included and 23 patients had efficacy information up to Jan 2024. The median follow-up time was 264 days (interval: 36-491 days). The objective response rate (ORR) and disease control rate (DCR) was 65.2% and 91.3%, respectively. All the patients haven’t reached the time to deterioration and the progression free survival(PFS) and overall survival is not reach. EORTC QLQ-LC30 showed general health status scale and functional scales increased and symptom scales decreased during aumolertinib treatment. Symptom scales assessed by EORTC QLQ-LC13 showed cough, sore mouth or tongue, chest pain, arm or shoulder pain and pain of other sites, were improved significantly after aumolertinib treatment (P < 0.05). Conclusions: General health status, functional status and key symptoms improved from baseline in patients with advanced NSCLC receiving aumolertinib as first-line treatment. The ORR and DCR in our study was comparable in those showed the AENEAS trial.
A retrospective study of tislelizumab combined with bevacizumab, pemetrexed, and carboplatin in driver-gene mutated advanced non-squamous non-small cell lung cancer after tyrosine kinase inhibitors failure.
Authors: He Sisi , Ma Hu , Meng Mi , Tang Yang , Qu Wendong , Han Xu , Chen Cheng
Published: July 2024

e20620

Background: Overcoming resistance to tumor targeted therapies is a major challenge in the management of driver-gene mutated non-small cell lung cancer (NSCLC). Recent clinical trials suggested that the combination approach of immunotherapy, bevacizumab and platinum-based chemotherapy was effective for driver-gene mutated NSCLC after tyrosine kinase inhibitors (TKIs) failure. Our retrospective study was aimed to examine the efficacy and safety of tislelizumab (TIS) combined with bevacizumab plus chemotherapy for advanced driver-gene mutated non-squamous NSCLC (nsq NSCLC) who had failed to TKIs therapies. Methods: We retrospectively collected medical records of driver-gene mutations advanced nsq NSCLC who had failed to TKIs therapies in the Affiliated Hospital of Zunyi Medical University and Second Affiliated Hospital of Zunyi Medical University from January 2021 to December 2023. The participants were sorted into two groups. Pts in TBCP group received TIS combined with bevacizumab, carboplatin and pemetrexed (BCP) for six cycles, followed by TIS with pemetrexed as maintenance therapy. Pts in BCP group received BCP regimen for six cycles, followed by pemetrexed as maintenance therapy. The primary endpoint was progression-free survival (PFS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. Results: A total of 12 pts were enrolled (6 pts in TBCP group and 6 pts in BCP group). In TBCP group, there was one patient with EGFR exon 19del, KRAS, BRAF V600 mutation and RET fusion, respectively. 2 pts harbored EGFR exon 21 L858R mutations. In BCP group, 4 pts harbored EGFR exon 19del, 1 patient with exon 21 L858R, and 1 patinet with BRAF V600 mutation. All pts were failed to previous TKI therapy. 3 pts (50%) had progression after two systemic treatment lines in ABCP group. 4 pts(66.7%) had progressive disease after at least two systemic regimen. As of 6 February 2024 (median follow-up, 18.6 months), significantly longer PFS was observed in TBCP group compared with BCP group (HR = 0.269 [95% CI: 0.068-1.065], p = 0.0080). Median PFS was 14.20 months (95% CI: 0.5010-5.379) and 8.65 months (95% CI: 0.1859-1.996) in TBCP group and BCP group, respectively. A higher ORR assessed was observed with TBCP group (66.7%) compared with BCP group (33.3%). The DCR were both 100% in two groups. Median OS was not reached. Grade 3-4 TRAEs occurred in 1 and 2 pts in TBCP group and BCP group, respectively. Conclusions: TIS combined with bevacizumab, carboplatin and pemetrexed has shown a promising anti-tumor efficacy with manageable safety profile for TKI failure driver-gene mutations advanced nsq NSCLC. However, these findings still need to be further confirmed by prospective clinical trials with larger sample sizes.
Immunotherapy in stage IV non-small cell lung cancer according to racial characteristics and community of residence.
Authors: Chang Annie , Untalan Matthew , Flores Raja Michael , Taioli Emanuela
Published: July 2024

e20621

Background: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer mortality worldwide. The advent of immunotherapy has transformed treatment paradigms for NSCLC. However, the use and effectiveness and immunotherapy may differ across racial groups and other sociodemographic factors, including sex, comorbidities, and community of residence. Our study analyzed disparities in immunotherapy receipt and overall survival among patients with stage IV NSCLC. Methods: Patients diagnosed with stage IV NSCLC from 2014 through 2016 were identified using the Surveillance Epidemiology, and End Results (SEER)-Medicare linked dataset. Immunotherapy receipt was compared across racial groups: non-Hispanic Whites, Blacks, Asians, Hispanics, and Native Americans. A multivariable logistic regression model evaluated associations between immunotherapy receipt and demographic and clinical variables including age, sex, marital status, Charlson comorbidity index, and histology. A multivariable Cox proportional hazards model assessed associations between these variables and overall survival. Results: Among 21,444 patients, the majority (78.6%) were White, while 10.7% were Black, 4.9% were Asian, 1.6% were Hispanic, and 0.2% were Native American. The efficacy of immunotherapy treatment was present across races, associating with better overall survival versus no immunotherapy (adjusted HR: 0.54, 95% CI: 0.49-0.59). After accounting for community of residence, race remained a significant factor in immunotherapy receipt (type 3 p-value: 0.028). Further adjustment for other covariates revealed that Black patients had significantly lower odds of receiving immunotherapy than White patients (adjusted OR: 0.64, 95% CI: 0.47-0.87). While Hispanics and Asians also had lower rates of receiving immunotherapy, these differences were not statistically significant. Asian patients exhibited higher overall survival compared to other races (adjusted HR: 0.88, 95% CI: 0.82-0.95). Conclusions: Use of immunotherapy for stage IV NSCLC is substantially lower among Blacks and other minority groups compared to Whites, indicating racial disparities in access to novel lung cancer treatments. Patients treated in urban areas are more likely to receive immunotherapy, underscoring the need to expand consistent access to efficacious treatments for advanced NSCLC. Ensuring equal access to effective treatments such as immunotherapy, regardless of race or community of residence, has the potential to improve outcomes and reduce racial disparities in lung cancer survival.
A medical school curriculum to foster the physician-patient relationship through narrative medicine.
Authors: Yao Johnathan , Hunter Cameron , Jaber Chehayeb Rachel , Sanft Tara B. , Prsic Elizabeth Horn , Dunne Dana , Kang-Giaimo Angela
Published: July 2024

e21015

Background: Narrative Competence is the ability to acquire, interpret and act on the stories of others.[1] Developing this skill can also improve health care practitioner’s sense of empathy and satisfaction with their work.[2] This study’s purpose is to evaluate the impact of a narrative medicine curriculum on medical students’ sense of connection to their patients and humanism in medicine. Methods: During the 2023 academic year, a narrative medicine assignment was introduced to the internal medicine oncology clerkship curriculum at the Yale School of Medicine. Third year medical students attended a training session on narrative medicine skills, interviewed a patient and wrote the patient’s story, and attended a session to read their written narrative. A survey was distributed to students asking for their reflections on the doctor patient relationship and the role of humanism in improving well-being and reducing burn out. Responses were de-identified and thematic analysis of responses was conducted. Results: 58 students participated in the training sessions and 11 (19%) completed a post-workshop free text survey with 5 questions reflecting on the doctor-patient relationship, the role of humanism in medicine, and the curriculum itself. Common themes that emerged include 1) how strong doctor-patient relationships makes medicine more meaningful, uplifting and enjoyable, 2) how seeking out a patient’s story is essential to the doctor-patient relationship and to optimal quality care, and 3) importance of doctor’s exhibiting care and sensitivity and placing diseases in context of their patients’ stories. Reflecting on the role of humanism in medicine, students reported that 1) taking the time to know your patients makes medicine rewarding, meaningful and worthwhile, 2) allows you to empathize and connect with patients more through recognizing their humanity and vulnerability and putting their frustrations in context, and 3) could be healing to both patient and provider. Further directions: Students suggested making the program mandatory, expanding to include pre-clerkship students and students on other clerkships, and providing more time and structure to facilitate interviewing patients and writing up their stories. Conclusions: A curriculum incorporating narrative medicine was effectively integrated and well-received by students and fostered an awareness of the rewards of listening to patient stories. References: [1] Charon R. The patient-physician relationship. Narrative medicine: a model for empathy, reflection, profession, and trust. JAMA. 2001;286(15):1897-1902. doi:10.1001/jama.286.15.1897; [2] Milota MM, van Thiel GJMW, van Delden JJM. Narrative medicine as a medical education tool: a systematic review. Med Teach. 2019;41(7):802-810. doi:10.1080/0142159X.2019.1584274.
The impact of an inclusion council in an independent community oncology practice.
Authors: Fleming Mark T. , Lyons Kristina , Poole Roshonda , Richards Margot , Hepburn Sonia , Ali-Spencer Tahj , Lewis Tifany
Published: July 2024

e21018

Background: Mainly present in academic hospital centers, Diversity Equity, and Inclusion (DEI) efforts have been largely left out of private practice. We previously reported on the impact of DEI training at VOA after our initial launch of the Inclusion Council in August 2020. VOA’s Inclusion Council continues its mission to further advancements in promoting a safe inclusive environment in the private practice setting. Methods: The methodology employed involved the administration of an anonymous comprehensive nine-question survey by the VOA Inclusion Council to assess the effectiveness of its ongoing efforts since its inaugural launch in 2020. The survey was meticulously crafted to capture the nuanced insights from employees regarding their knowledge and perceptions of the Inclusion Council’s impact on workplace dynamics. The questions were designed to gauge the extent to which the Council has successfully fostered an inclusive environment, promoted diversity, and identified any potential challenges faced by employees. The survey was distributed to all employees, ensuring a diverse range of perspectives was considered. This methodological approach aimed to provide a robust understanding of the council’s effectiveness through the direct input of those within the organization, thereby contributing valuable data for the evaluation of its initiatives. Results: Summary of employee respondent’s views on Inclusion Council helping foster a culture of inclusion in the workplace. A total of 147 employees responded. 68% of respondents agreed or strongly agreed that the Inclusion Council helped foster a culture of inclusion in the workplace. Conclusions: An Inclusion Council, focused on DEI efforts, can help foster a culture of inclusion in the workplace. Veteran and new employees agreed the Inclusion Council has helped foster a culture of inclusion in our community oncology practice. [Table: see text]
Case series: Outcomes of immunotherapy in locally advanced and metastatic cutaneous squamous cell carcinoma in Lakes and Waikato region.
Authors: Yogarajah Ahrabie , Wickham Alistair , Hari Dass Prashanth
Published: July 2024

e21529

Background: Cutaneous squamous cell carcinomas (CSCC) have an incidence of 425 per 100,000 in New Zealand (1). 5% progress to locally advanced or metastatic disease. Immunotherapy is unfunded for this indication despite excellent response and safety profile (2). The objective was to evaluate real world outcomes of patients who managed to access immunotherapy. Methods: Review of referrals to medical oncology in the Lakes & Waikato region between 1 August 2017 to 31 August 2022 with unresectable locally advanced or metastatic CSCC who had immunotherapy. Patients who were not referred to medical oncology, could not afford immunotherapy and/or unsuitable for a clinical trial were excluded from analysis. Results: 13/15 (86.7%) reviewed were male. Mean age was 71. 7 were locally advanced and 8 were metastatic. 14 self-funded pembrolizumab (11 first line, 3 second line). 1 accessed immunotherapy via a trial. 12 (80%) had significant responses; 3 achieved a complete response and 9 achieved a partial response. Median duration of response was not reached, with a median number of 18 cycles delivered. Median follow up was 23.8 months. 9 (60%) remain alive with ongoing response. 6 died on treatment; 3 from non-malignancy and non-treatment related causes. No Grade IV toxicities were observed. Grade III transaminitis was seen in one patient. Grade I-II toxicities seen in 11 (73.3%), including arthralgia (26.7%), fatigue (20%), transaminitis (13.3%), rash (20%), hypothyroidism (6.7%), diarrhoea (6.7%) and dyspnoea (6.7%). Conclusions: Despite an elderly & comorbid cohort, immunotherapy resulted in durable responses and excellent safety profile, highlighting the unmet need for immunotherapy funding in New Zealand. More understanding is required around the different responses to anti-PD1 therapies for the same malignancy type. (1) Pondicherry A, et al. The burden of non-melanoma skin cancers in Auckland, New Zealand. Australas J Dermatol. 2018 Aug; 59(3):210-213 (2) Hughes B, et al. Pembrolizumab for locally advanced and recurrent/metastatic cutaneous squamous cell carcinoma (KEYNOTE-629 study): an open-label, nonrandomized, multicentre, phase II trial. Ann Oncol. 2021;32(10):1276-1285.