bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive biomarkers for treatment with amivantamab plus lazertinib among EGFR-mutated NSCLC in the post-osimertinib setting: Analysis of tissue IHC and ctDNA NGS.
Authors: Besse Benjamin , Baik Christina S , Marmarelis Melina Elpi , Sabari Joshua K. , Goto Koichi , Shu Catherine A. , Lee Jong-Seok , Ou Sai-Hong Ignatius , Cho Byoung Chul , Waqar Saiama Naheed , Swalduz Aurélie , Tomasini Pascale , Bauml Joshua Michael , Curtin Joshua C , Wang Songbai , Jatkoe Tim , Gormley Michael , Trani Leonardo , Knoblauch Roland Elmar , Felip Enriqueta 
Published: June 2023

9013 Background: Amivantamab (ami) is a bispecific antibody targeting EGFR and MET with immune cell-directing activity, and lazertinib (laz) is a brain-penetrant, third-generation EGFR tyrosine kinase inhibitor. In a previous report, the overall response rate (ORR) of ami+laz in the post-osimertinib (osi) setting was 36%, with median duration of response of 9.6 months (Bauml JCO 2021; 39:15_suppl, 9006). Exploratory analyses suggested certain immunohistochemistry (IHC) and ctDNA-based next-generation sequencing (NGS) biomarkers may enrich for response. A prospective study was conducted to further evaluate these potential biomarkers. Methods: CHRYSALIS-2 (NCT04077463), an ongoing phase 1/1b study, examines the efficacy (ORR per RECIST v1.1) of ami+laz in patients (pts) with EGFR-mutated NSCLC. Cohort D enrolled osi-relapsed, chemotherapy-naïve pts with EGFR exon 19 deletion or L858R mutated advanced NSCLC who had tumor tissue for IHC staining and plasma for ctDNA NGS collected after their most recent therapy. Training and validation subsets identified biomarker criteria and predictive validity, respectively. A Bayesian posterior probability (biomarker positive group ORR is ≥35% and negative group ORR is ≤20%) was predefined to be ≥85% for acceptance. Results: There were 101 response-evaluable pts enrolled in Cohort D. A total of 87 pts had detectable baseline ctDNA and 77 pts had evaluable MET IHC. The training set (n = 50) identified IHC-based MET expression of 3+ staining on ≥25% of tumor cells (MET+) as a potential predictive biomarker, and the validation set (n = 27) confirmed these results. Of those with MET IHC data, 28/77 (36%) were MET+. The overall ORR for MET+ was 61% (95% CI, 41–78) and 12% (95% CI, 5–25) for MET-, with median PFS for MET+ not reached (95% CI, 4.3–NE) vs 4.1 months (95% CI, 2.8–5.7) for MET-. NGS evaluation of ctDNA did not identify predictive biomarkers meeting predetermined criteria. Of note, only 1 pt was identified by ctDNA as having MET amplification (the pt was also MET+ by IHC). Further details will be provided at the time of presentation. Conclusions: MET+ by IHC may be a predictive biomarker for response to ami+laz in the post-osi, chemotherapy-naïve setting. In contrast, molecular profiling with ctDNA failed to identify a subgroup of pts more likely to benefit. Ami+laz represents a potential chemotherapy-free option for pts with EGFR-mutated advanced NSCLC who have progressed on osi and are also MET+ by IHC. Clinical trial information: NCT04077463 .
FAK inhibition with novel FAK/ALK inhibitor APG-2449 could overcome resistance in NSCLC patients who are resistant to second-generation ALK inhibitors.
Authors: Ma Yuxiang , Zhao Hongyun , Chen Jianhua , Song Zhengbo , Zhao Yanqiu , Guo Yubiao , Wu Gang , Zhou Wenwei , Yu Xiaoqing , Gao Fangfang , Zhang Ruiguang , Fang Jian , Lin Xiaoyan , Tian Xiaohong , Tu Yanhua , Yu Juan , Liu GuangLin , Zhai Yifan , Zhang Li 
Published: June 2023

9015 Background: APG-2449 is a novel, orally active FAK inhibitor and an ALK/ROS1 tyrosine kinase inhibitor (TKI) that has shown potent activity in preclinical models. It had been demonstrated that APG-2449 was well tolerated, and preliminary efficacy was observed in pts who were resistant to second-generation ALK/ROS1+ inhibitors (Zhao H et al. J Clin Oncol 2022; 40:9071). We provide updated safety and efficacy results and potential mechanisms of action(s) of this therapy. Methods: After the RP2D was determined as 1,200 mg daily (QD), NSCLC pts were enrolled into 2 dose expansion cohorts. Cohort 1 included pts who were resistant to second-generation ALK/ROS1+ TKIs. Cohort 2 included those who were ALK or ROS1+ TKI naïve. Results: As of December 9, 2022, 130 pts enrolled (median [range] age 53 [21-78] years; 53.8% female) with NSCLC, mesothelioma, or ovarian cancer were treated with APG-2449 at doses ranging from 900 to 1,500 mg. A total of 117 (90%) pts experienced treatment-related adverse events (TRAEs). The most frequent TRAEs included elevated blood creatinine (43.8%), ALT (40.8%), and AST (33.1%) levels, as well as gastrointestinal disorders: nausea (25.4%), vomiting (21.5%), and diarrhea (21.5%). A total of 17 (13.1%) TRAEs were grade ≥ 3. In a subgroup of pts with TKI-naïve NSCLC (n = 33; 31 with efficacy evaluable), the overall response rate (ORR) and the disease control rate (DCR = CR + PR + SD) were 70.6% (12/17) and 88.2% (15/17), respectively, in ROS1+ treatment naïve pts; the ORR and DCR were 78.6% (11/14) and 100% (14/14) in ALK+ treatment naïve pts. Of 27 NSCLC pts resistant to second-generation ALK inhibitors, 7 were observed with PR (7/27; 25.9%) during APG-2449 treatment at RP2D. In this subgroup, compared to baseline, pts who experienced PR showed lower phosphorylated FAK (pFAK) levels in peripheral blood mononuclear cells (PBMCs) by Day 28 (24 hours after dosing on D28) than pts who experienced SD. Furthermore, pts with progressive disease showed an increase of PBMC pFAK levels on D28 compared to baseline, indicating that APG-2449 could inhibit FAK phosphorylation. Pts with higher pFAK expression in tumor tissues at baseline tended to achieve better clinical responses than those with lower pFAK expression post APG-2449 treatment. Conclusions: APG-2449 showed a favorable preliminary safety profile and antitumor efficacy in pts with NSCLC. Preliminary efficacy was observed in those whose disease was TKI naïve and resistant to second-generation ALK inhibitors. FAK inhibition could be a novel approach to overcome ALK resistance in pts with NSCLC who are resistant to second-generation ALK inhibitors. Internal study identifier: APG2449XC101. Clinical trial information: NCT03917043 .
Efficacy and safety of encorafenib (enco) plus binimetinib (bini) in patients with BRAF V600E-mutant (BRAFV600E) metastatic non-small cell lung cancer (NSCLC) from the phase 2 PHAROS study.
Authors: Riely Gregory J. , Smit Egbert F. , Ahn Myung-Ju , Felip Enriqueta , Ramalingam Suresh S. , Tsao Anne S. , Johnson Melissa Lynne , Gelsomino Francesco , Esper Raymond M. , Nadal Ernest , Offin Michael , Provencio-Pulla Mariano , Otterson Gregory Alan , Dagogo-Jack Ibiayi , Alcasid Ann , Usari Tiziana , Wilner Keith D. , Pathan Nuzhat , Johnson Bruce E. 
Published: June 2023

9018 Background: The combination of dabrafenib, a BRAF inhibitor, and trametinib, a MEK inhibitor, is a current standard of care for patients (pts) with BRAFV600E NSCLC. We report efficacy and safety of enco+bini in pts with BRAFV600E metastatic NSCLC. Methods: PHAROS is an ongoing, open-label, single-arm, phase 2 study that enrolled pts with BRAFV600E metastatic NSCLC who had measurable disease by RECIST 1.1 and Eastern Cooperative Oncology Group performance status of 0 or 1, and who were either treatment-naive or had received 1 prior therapy (chemotherapy, monotherapy, or combination immunotherapy) for metastatic disease. Exclusion criteria included prior treatment with a BRAF or MEK inhibitor. Pts received enco 450 mg QD + bini 45 mg BID administered orally in 28-day cycles. The primary endpoint was confirmed objective response rate (ORR) by independent radiology review (IRR). Secondary endpoints included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), and time to response (TTR), all by IRR, and safety. Exploratory endpoints included biomarker assessments. Results: At the data cutoff (Sep 22, 2022), 98 pts (59 treatment-naive, 39 previously treated) received enco+bini. The median duration of treatment was 9.2 months with enco and 8.4 months with bini. Treatment is ongoing in 34% of the pts; 38% permanently discontinued due to disease progression and 18% due to adverse events (AEs). The ORR (95% CI) by IRR was 75% (62, 85) in treatment-naive and 46% (30, 63) in previously treated pts. Secondary endpoints are shown in the table. The most frequent (≥30%) treatment-related AEs (TRAEs) were nausea (50%), diarrhea (43%), and fatigue (32%). AEs led to permanent discontinuation of enco+bini in 15% of pts and dose reductions in 24% of pts. One grade 5 TRAE of intracranial hemorrhage was reported. Next-generation sequencing analysis was conducted with archival tumor biopsies from 48 treatment-naive and 32 previously treated pts. The most frequent genomic alterations, in addition to BRAFV600E, were SETD2 and TP53 (43% each), SMAD4 (21%), ATM, MLL2, CSF1R, and SMARCA4 (14% each), and CDKN2A (11%). Conclusions: The combination of enco+bini showed meaningful clinical benefit in treatment-naive and previously treated pts with BRAFV600E metastatic NSCLC. The safety profile of enco+bini was generally consistent with that established for pts with BRAFV600E/K melanoma. ClinicalTrials.gov: NCT03915951. Clinical trial information: NCT03915951 . [Table: see text]
MSH3 and MSH6 gene polymorphisms: Association with lung cancer susceptibility and prognostic value in patients with NSCLC undergoing platinum-based chemotherapy.
Authors: Singh Navneet , Singh Sidhartha , Sharma Parul , Sharma Siddharth 
Published: June 2023

9031 Background: DNA mismatch repair (MMR) pathway is responsible for recognizing and repairing errors (insertion, deletion and misincorporation of bases) occurring during DNA replication and recombination. Single nucleotide polymorphisms (SNPs) in MSH3 and MSH6 genes are related to development of various cancers. SNPs of particular interest include rs26279 G > A polymorphism for MSH3 and rs3136228 557G > T polymorphism for MSH6. In this cohort study, we evaluated the association of MSH3 (rs26279) and MSH6 (rs3136228) SNPs with occurrence of lung cancer (LC), baseline demographic and clinical characteristics and with overall survival (OS) amongst LC patients undergoing platinum-based doublet chemotherapy. Methods: 500 LC patients and 500 healthy controls were enrolled. Genomic DNA was isolated from 4ml of peripheral blood using a phenol-chloroform extraction procedure and genotyping of patients and controls was performed using PCR-RFLP. All enrolled patients had pathologically confirmed LC. Written informed consent was obtained from all enrolled subjects and the study was approved by institutional ethics committee. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated using logistic regression analysis. Kaplan-Meier method was used for OS analysis and (multivariate) Cox regression models to obtain (adjusted) hazards ratios (HRs). Results: Mean age (61 years) was similar for cases and controls. Compared to controls, LC cohort had higher prevalence of non-smokers (20% vs. 10%), female sex (20% vs. 9%) and smoking pack-years (mean 20.8 vs. 13.8). Majority of LC patients had metastatic disease (54%) and ECOG performance status of 0-1 (45%) or 2 (40%). Adenocarcinoma and squamous were equi-prevalent (41% each). Mutant genotype (TT) for MSH6 polymorphism was more frequent in LC patients (OR = 1.43; 95% CI = 1.01 – 2.03; p = 0.03) with the association more marked in adenocarcinoma histology (OR = 1.74; 95% CI = 1.05 – 2.93; p = 0.03). For non-smokers, mutant genotype (TT) for MSH6 polymorphism was associated with a 3-fold increased risk of LC (OR = 3.22; 95% CI = 1.26 – 8.18; p = 0.01). Amongst females, heterozygous genotype (GA) for MSH3 polymorphism was more frequent amongst LC cases (24%) than controls (16%) (OR = 2.35, 95% CI = 0.85 – 6.52, p = 0.04). Patients treated with docetaxel-platinum chemotherapy and carrying heterozygous (GT) genotype for MSH6 polymorphism had worse OS (median 4.9 vs 9.1 months; adjusted HR = 2.3; p = 0.03). No association was observed between MSH3 (rs26279) and MSH6 (rs3136228) polymorphisms and other baseline clinical/demographic characteristics. Conclusions: The results of this cohort study suggest that MSH3 and MSH6 polymorphisms are involved in modulating the risk towards LC occurence. MSH6 polymorphism is also associated with higher mortality amongst patients treated with docetaxel-platinum chemotherapy.
Impact of genomic alterations measured in circulating tumor DNA (ctDNA) on clinical response to telisotuzumab vedotin treatment in patients with non-small cell lung cancer (NSCLC).
Authors: Camidge D. Ross , Baijal Shobhit , Vasilopoulos Athanasios , Ratajczak Christine , Looman Jim , Li Martha , Ansell Peter J. , Lu Shun 
Published: June 2023

9032 Background: The antibody-drug conjugate telisotuzumab vedotin (Teliso-V) is composed of the c-Met–targeting antibody telisotuzumab (ABT-700) linked to the microtubule inhibitor monomethyl auristatin E. In the LUMINOSITY study (NCT03539536), efficacy of Teliso-V was seen in patients (pts) with EGFR wildtype nonsquamous NSCLC and c-Met overexpression (≥25% tumor cells at 3+ intensity by IHC); overall response rate: 36.5%. Data are limited on whether specific driver oncogene states affect responses. We investigated genomic alterations in relation to response to Teliso-V in this population. Methods: Pts received 1.9 mg/kg Teliso-V monotherapy once every 2 weeks in LUMINOSITY. ctDNA was isolated from plasma collected at different timepoints. The PGDx elio plasma complete assay was used to identify genomic alterations in ctDNA samples. This assay included 521 genes for single nucleotide variants and insertion-deletion mutations, 38 for amplifications (amp), and 21 for translocations. Results: In total, 52 pts were included in the study; ctDNA from 48 pts was analyzed. The overall response rate among pts with ctDNA results was 37.5% (18 pts with partial response) compared with 36.5% for the ITT population of 52 pts. Genomic alterations are listed in the Table.Three out of 4 pts with MET amp at baseline responded, accounting for 17% of total responses. The observed MET amp frequency in this MET IHC preselected cohort was 8%, which is similar to the prevalence observed in tissue analysis by FISH. Of note, 1 nonresponder harbored a MET ex14del mutation at baseline, and a responder had a low-frequency mutation detected at the final visit. Mutations in KRAS were the most common genomic alteration and were detected in 13 (27%) pts at baseline. Three pts with a KRAS mutation were responders; among these, 2 out of 3 had a KRAS G12C mutation (seen in 3 pts total). Response rates were higher in pts with MET amp (75%; 95% CI: 0.30, 0.95) vs those without MET amp (34%; 0.22, 0.49), and higher in pts without KRAS mutations (43%; 0.28, 0.59) vs those with KRAS mutations (23%; 0.08, 0.50); however, confidence intervals were wide and larger sample sizes are needed. Conclusions: MET amp occurred more frequently in responders; however, Teliso-V activity was not restricted to these pts, as most responders were not MET amplified. Specific genomic alterations beyond MET may influence clinical response. The current analysis demonstrated numeric differences between pts with identified drivers who did or did not respond to Teliso-V. Additional research on this topic is needed in larger pt cohorts and/or with tissue-based NGS analyses. [Table: see text]
Exploring the potential of combination immune checkpoint strategies in non-small cell lung cancer (NSCLC).
Authors: Desai Aakash , Subbiah Vivek , Dimou Anastasios , Deshane Jessy , Goliwas Kayla , Ponnazhagan Selvarangan , Das Devika Govind , Khalil Maya , Lo Ying-Chun , Lin Edwin H 
Published: June 2023

9037 Background: The clinical outcomes for patients with NSCLC remain suboptimal despite recent advancements in anti-PD-1/PD-L1 immunotherapies. Thus, identification of rational combinations of novel immune checkpoint (IC) strategies is imperative. This study aimed to comprehensively characterize the expression of IC targets to inform drug development and design effective combinatorial strategies, to advance the search for optimized therapies for NSCLC. Methods: We analyzed the differential gene expression of IC targets in 537 primary lung adenocarcinoma (LUAD) samples and 59 normal lung tissue samples pre-immunotherapy receipt using RNA-sequencing data from The Cancer Genome Atlas. Gene expression of IC-targets including PDCD1 (PD-1), CD274 (PD-L1), CTLA4, TIGIT, LAG3, HAVCR2 (TIM-3), VSIR (VISTA), ICOS, CD276 (B7-H3), BTLA, IDO1, KLRD1 (CD94/NKG2A), NT5E (CD73), TNFRSF4 (OX-40), TNFRSF18 (GITR), and TNFRSF9 (4-1BB) were obtained. Differential gene expression was determined intra-tumorally by comparison of transcripts per million and inter-tumorally using the DESeq2 algorithm. Log2 fold change >0.5 and false discovery rate adjusted P<0.05 were used as criteria for significant differential expression. Hierarchical clustering was used to identify subsets of tumors with similar profiles of IC-targetable gene expression. Results: Tumors showed significantly increased expression of TNFRSF18 (GITR), NT5E (CD73), TNFRSF9 (4-1BB), LAG3, TIGIT, CTLA4, PD-1, BTLA, B7-H3, and OX-40 (Table 1). On the other hand, tumors exhibited significant downregulation of CD274 (PD-L1), HAVCR2 (TIM-3), ICOS, KLRD1 (CD94/NKG2A), and VSIR (VISTA). Hierarchical clustering revealed recurrent patterns of IC gene overexpression which were characterized by: 1) IDO1-hi, 2) CD276-mid + TNFRSF18-mid, 3) VSIR-hi, 4) CD276-hi, 5) NT5E-hi, and 6) CD276-mid + NT5E-mid. Interestingly, patterns of IC gene expression distinguish tumors from controls. Of note, high VSIR expression was specific to normal tissue rather than tumors. Conclusions: Our study identified many IC targetable genes that were significantly overexpressed in tumors. However, subsets of tumors showed distinct and segregable combinations of overexpressed IC genes. These results suggest heterogeneous mechanisms of immune evasion in NSCLC, which may explain suboptimal outcomes with anti-PD-1/PD-L1 based strategies in this patient population. Our findings emphasize the importance of biomarker-guided approaches for the optimal selection of ICs and the development of rational combinatorial immunotherapies in NSCLC.
Co-mutational status and PD-L1 expression in KRAS mutant non-small cell lung cancer (NSCLC): Role in treatment selection and association with clinical outcomes.
Authors: Khan Hina , Judd Julia , Xiu Joanne , Ullah Asad , Raval Girindra Ghanshyam , Ma Patrick C. , Nieva Jorge J. , Radovich Milan , Oberley Matthew James , Kim So Yeon , Mamdani Hirva , Raez Luis E. , Vanderwalde Ari M. , Halmos Balasz , Borghaei Hossein , Liu Stephen V. , Abdel Karim Nagla Fawzy 
Published: June 2023

9038 Background: In NSCLC, different KRAS mutations (mt) define unique subgroups and certain co-mutations (co-mt) could have prognostic and therapeutic implications. Retrospective studies associate poor prognosis with co-mts in STK11 and KEAP1 with KRAS. It is unclear if PD-L1 expression and co-mt in KRAS mt NSCLC impacts outcomes. Methods: Molecular profiles of 27748 NSCLC tumors were tested with next-generation sequencing (Caris Life Sciences, Phoenix, AZ) and classified by KRAS mt. PD-L1 IHC (22C3) was reported as TPS. Real-world post-immunotherapy (IO) overall survival (OS) was obtained from insurance claims and calculated from start of an immune check-point inhibitor (with or without chemotherapy) to the last day of follow-up. Results: In all, 7634 (28%) samples had a KRAS mt; most common being G12C (11%), G12V (5.3%), G12D (3.9%) and G13X (2.0%). The most frequent co-mt was KRAS-TP53 (KP) (46%), similar in all KRAS subtypes. KRAS-STK11(KL) was in 23% of KRAS mt, enriched in G13X (33%) and lowest in G12D (16%). KRAS-KEAP1(KK) was co-mt in 10% of KRAS mt, highest in G13X (16%) and lowest in G12D (8%). KRASmt/ STK11wt/ KEAP1wt/ TP53wt (K only) was 27% of KRAS mt, highest in G12D (36%) and lowest in G13X (16%). A small subgroup, 5.6% was KRAS-STK11-KEAP1 co-mt (KKL). The majority of pts in the KL (61%), KK (52%) and KKL (62%) cohorts had TPS <1%. In 1723 KRAS mt NSCLC pts treated with IO, KL, KK and KKL had significantly worse post-IO OS than KP and K only (table); KKL had the lowest OS. In the TPS≥1% KRAS mt group, KL, KK and KKL had worse post-IO OS than KP and K-only. In TPS<1% group, KL and KK had poor post-IO OS and K-only had favorable outcomes. However, KP had worse post-IO OS compared to K-only in TPS<1%. In G12C and G12V, similar trend with worse post-IO OS in KL, KK and KKL, compared to KP and K only was noted. Conclusions: We report a large real-world dataset evaluating outcomes with check-point inhibitors in NSCLCs with KRAS and specific co-mts. KL, KK and KKL subgroups demonstrate universally poor outcomes in all KRAS subtypes irrespective of PD-L1. Pts with KP co-mts have adverse post-IO outcomes in TPS<1% but favorable in TPS≥1%. TPS score remains a predictive marker of IO outcomes in KP, but not in KL, KK and KKL. These observations emphasize that both PD-L1 and co-mts have a clear association with clinical outcomes in KRAS-mt NSCLC, and must be used in predictive models for individualized therapy. [Table: see text]
Pre-treatment plasma-informed circulating tumor DNA detection as an early identification of therapeutic benefit for patients with untreated advanced lung squamous cell carcinoma.
Authors: Jiang Tao , Zhang Jiao , Li Feifei , Xu Li-Di , Ma Ting , Yang Ying , Huang Yu S. , Chen Weizhi , Zhou Caicun 
Published: June 2023

9041 Background: Circulating tumor DNA (ctDNA) detection as a promising prognostic factor to assess treatment response has been widely studied with customized tumor-informed strategies, the application of which was limited by the inaccessibility for tumor biopsies in a substantial proportion of patients. To overcome this challenge, we presented a proof-of-concept study for the development of a novel personalized pre-treatment plasma-informed next generation sequencing (NGS) panel and investigated its prognostic value for first line treatment in patients with advanced lung squamous cell carcinoma (LUSC). Methods: Paired plasma and white blood cell (WBC) samples were collected from 227 of stage IIIB-IV LUSC patients who were treated with first line either chemotherapy or chemotherapy plus PD-1 blockade at pre- and post-treatment. Somatic mutations in pre-treatment plasma were identified with a 769-gene based NGS panel (Genecast, Wuxi, China) followed with germline or clonal hematopoietic variants filtering by referring to the WBC samples. Positive variants detected in the pre-treatment plasma served as a basis for personalized variants tracking in post-treatment plasma. ctDNA kinetics was measured by plasmaDelta (Δgenevaf=((post-treatment genevaf – pre-treatment genevaf) / pre-treatment genevaf; genevaf was defined by variant allele frequency for each individual gene). Progression-free survival (PFS) as the primary endpoint and overall survival (OS) as the secondary endpoint were assessed. Results: ctDNA positivity was observed in 80% (182/227) of pre-treatment samples and subsequently 54% (99/182) of post-treatment samples. ctDNA positivity at post-treatment was shown to be a significant predictor for both PFS and OS in the whole group as well in the sub-treatment groups (Table). After adjusting for clinicopathologic variables, ctDNA positivity remained significantly associated with both worse PFS and OS (PFS: HR = 2.3, P <0.001 and OS: HR= 2.56, P <0.001). ctDNA kinetics further identified a worse treatment response group. Patients with high plasmaDelta had remarkably worse outcomes than patients with low plasmaDelta (PFS: HR =4.8; 95%CI=2.8-8.3; P < 0.001 and OS: HR=2.8; 95%CI=1.7-4.6; P <0.001). Conclusions: These results demonstrated the feasibility of pre-treatment plasma-informed ctDNA detection and kinetics for monitoring treatment response in LUSC patients whose tumor biopsies were unavailable. [Table: see text]