Cancer Research and Treatment

Predictive Value of the nProfiler 1 Assay for the Efficacy of Adjuvant S-1-Based Doublet Chemotherapy in Stage III Gastric Cancer: A Post-Hoc Analysis of a Randomized Phase III Trial: Dong Ki Lee, Choong-kun Lee, Hyo Song Kim, Sun Jin Sym, Dae Young Zang, Ki Hyang Kim, Joo Han Lim, Hae Su Kim, Kyung Hee Lee, Heon Yung Gee, Sun Young Rha, Hyunki Kim, Minkyu Jung; Received July 25, 2024 Accepted November 9, 2024 Published online November 12, 2024; DOI: https://doi.org/10.4143/crt.2024.705 [Accepted]

Abstract PDF: Purpose
The nProfiler 1 Stomach Cancer Assay (nProfiler1), designed to predict responses to fluorouracil-based adjuvant chemotherapy, measures the expression of four gastric cancer target genes (GZMB, WARS, SFRP4, and CDX1). The randomized phase III POST trial aimed to compare the efficacies of two adjuvant S-1-based doublet chemotherapies: S-1 plus cisplatin (SP) and S-1 plus docetaxel (DS). This study aimed to validate the nProfiler1 assay using a distinct cohort from the POST trial.
Materials and Methods
The nProfiler1 assay stratifies patients into three groups (low-risk, intermediate-risk, and high-risk) using the prognostic single-patient classifier and two groups (chemotherapy-benefit and no-benefit) using the predictive single-patient classifier. The nProfiler1 assay was applied to formalin-fixed paraffin-embedded slides obtained from the POST trial. Disease-free survival (DFS) and overall survival (OS), including 5-year survival rates, were calculated for the enrolled patients.
Results
Of the 153 patients in the POST trial, 118 were included in the post-hoc analysis. With a median follow-up of 57.9 months, no significant difference in DFS or OS was observed between the SP and DS groups. The prognostic single-patient classifier predicted the OS in the SP group (p=0.0425) but not in the DS group (p=0.5940). The chemotherapy-benefit group exhibited numerically longer DFS than the no-benefit group in the SP and DS groups.
Conclusion
The nProfiler1 assay offers valuable insights into the prognosis and efficacy of adjuvant chemotherapy based on fluorouracil plus platinum doublet regimens but not docetaxel-containing regimens. Further validation with larger patient cohorts and different regimens is warranted.

255 View
31 Download

Differences in the Prognostic Impact between Single-zone and Multi-zone N2 Node Metastasis in Patients with Station-Based Multiple N2 Non–Small Cell Lung Cancer: Shia Kim, Geun Dong Lee, SeHoon Choi, Hyeong Ryul Kim, Yong-Hee Kim, Dong Kwan Kim, Seung-Il Park, Jae Kwang Yun; Received February 5, 2024 Accepted July 19, 2024 Published online July 22, 2024; DOI: https://doi.org/10.4143/crt.2024.120 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
The International Association for the Study of Lung Cancer suggests further subdivision of pathologic N (pN) category in non–small-cell lung cancer (NSCLC) by incorporating the location and number of involved lymph node (LN) stations. We reclassified patients with the station-based N2b disease into single-zone and multi-zone N2b groups and compared survival outcomes between the groups.
Materials and Methods
This retrospective study included patients with pN2 NSCLC who underwent lobectomy from 2006 to 2019. The N2 disease was subdivided into four categories: single-station N2 without N1 (N2a1), single-station N2 with N1 (N2a2), multiple-station N2 with single zone involvement (single-zone N2b), and multiple-station N2 with multiple zone involvement (multi-zone N2b). LN zones included in the subdivision of N2 disease were upper mediastinal, lower mediastinal, aortopulmonary, and subcarinal.
Results
Among 996 eligible patients, 211 (21.2%), 394 (39.6%), and 391 (39.3%) were confirmed to have pN2a1, pN2a2, and pN2b disease, respectively. In multivariable analysis after adjustment for sex, age, pT category, and adjuvant chemotherapy, overall survival was significantly better with single-zone N2b disease (n=125, 12.6%) than with multi-zone N2b disease (n=266, 26.7%) (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.49 to 0.90; p=0.009) and was comparable to that of N2a2 disease (HR, 1.12; 95% CI, 0.83 to 1.49; p=0.46).
Conclusion
Prognosis of single-zone LN metastasis was better than that of multiple-zone LN metastasis in patients with N2b NSCLC. Along with the station-based N descriptors, zone-based descriptors might ensure optimal staging, enabling the most appropriate decision-making on adjuvant therapy for patients with pN2 NSCLC.

543 View
53 Download

Locoregional Recurrence in Adenoid Cystic Carcinoma of the Breast: A Retrospective, Multicenter Study (KROG 22-14): Sang Min Lee, Bum-Sup Jang, Won Park, Yong Bae Kim, Jin Ho Song, Jin Hee Kim, Tae Hyun Kim, In Ah Kim, Jong Hoon Lee, Sung-Ja Ahn, Kyubo Kim, Ah Ram Chang, Jeanny Kwon, Hae Jin Park, Kyung Hwan Shin; Received February 23, 2024 Accepted July 11, 2024 Published online July 12, 2024; DOI: https://doi.org/10.4143/crt.2024.201 [Epub ahead of print]

Abstract PDF PubReader ePub: Purpose
This study aims to evaluate the treatment approaches and locoregional patterns for adenoid cystic carcinoma (ACC) in the breast, which is an uncommon malignant tumor with limited clinical data.
Materials and Methods
A total of 93 patients diagnosed with primary ACC in the breast between 1992 and 2022 were collected from multi-institutions. All patients underwent surgical resection, including breast-conserving surgery (BCS) or total mastectomy (TM). Recurrence patterns and locoregional recurrence-free survival (LRFS) were assessed.
Results
Seventy-five patients (80.7%) underwent BCS, and 71 of them (94.7%) received post-operative radiation therapy (PORT). Eighteen patients (19.3%) underwent TM, with five of them (27.8%) also receiving PORT. With a median follow-up of 50 months, the LRFS rate was 84.2% at 5 years. Local recurrence (LR) was observed in five patients (5.4%) and four cases (80%) of the LR occurred in the tumor bed. Three of LR (3/75, 4.0%) had a history of BCS and PORT, meanwhile, two of LR (2/18, 11.1%) had a history of mastectomy. Regional recurrence occurred in two patients (2.2%), and both cases had a history of PORT with (n=1) and without (n=1) irradiation of the regional lymph nodes. Partial breast irradiation (p=0.35), BCS (p=0.96) and PORT in BCS group (p=0.33) had no significant association with LRFS.
Conclusion
BCS followed by PORT was the predominant treatment approach for ACC of the breast and LR mostly occurred in the tumor bed. The findings of this study suggest that partial breast irradiation might be considered for PORT in primary breast ACC.

647 View
72 Download

Factors Associated with Postoperative Recurrence in Stage I to IIIA Non–Small Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation: Analysis of Korean National Population Data: Kyu Yean Kim, Ho Cheol Kim, Tae Jung Kim, Hong Kwan Kim, Mi Hyung Moon, Kyongmin Sarah Beck, Yang Gun Suh, Chang Hoon Song, Jin Seok Ahn, Jeong Eun Lee, Jae Hyun Jeon, Chi Young Jung, Jeong Su Cho, Yoo Duk Choi, Seung Sik Hwang, Chang Min Choi, Seung Hun Jang, Jeong Uk Lim, Korean Association for Lung Cancer, Korea Central Cancer Registry; Received January 19, 2024 Accepted July 8, 2024 Published online July 10, 2024; DOI: https://doi.org/10.4143/crt.2024.073 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
Recent development in perioperative treatment of resectable non–small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection.
Materials and Methods
Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee.
Results
A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors.
Conclusion
Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.

1,203 View
78 Download

Upfront Stereotactic Radiosurgery or Fractionated Stereotactic Radiotherapy in Elderly Patients with Brain Metastases from Non–Small Cell Lung Cancer: A Retrospective Analysis of a 10-Year Bi-institutional Experience: Myungsoo Kim, Jihye Cha, Hun Jung Kim, Woo Chul Kim, Jeongshim Lee; Received February 29, 2024 Accepted July 2, 2024 Published online July 3, 2024; DOI: https://doi.org/10.4143/crt.2024.223 [Epub ahead of print]

Abstract PDF PubReader ePub: Purpose
Stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) are increasingly used as initial therapies for brain metastases (BM). We aimed to assess the outcomes of SRS/FSRT in patients aged ≥ 65 years who had 1-10 BM from non–small cell lung cancer (NSCLC).
Materials and Methods
We retrospectively reviewed 91 elderly NSCLC patients with 222 BM who were treated with SRS/FSRT at two institutions between 2010 and 2020. The primary endpoint was overall survival (OS) after SRS/FSRT. In addition, in-field local control (IFLC) within the treated field was evaluated. Statistical analysis was performed to identify the prognostic factors affecting OS and IFLC.
Results
During a median follow-up of 18 months, the median OS was 32 months. The 1- and 2-year survival rates were 69.8% and 56.1%, respectively. In multivariate analysis, the NSCLC-specific graded prognostic assessment (GPA) score (p=0.007) and administration of systemic therapy (p=0.039) were defined as prognosticators affecting OS. The median IFLC period was 31 months, and the 1- and 2-year IFLC rates were 75.9% and 57.6%, respectively. The total BM volume (p=0.042) significantly affected IFLC. No severe adverse events were reported after SRS/FSRT.
Conclusion
SRS/FSRT is an effective upfront treatment option for BM arising from NSCLC in elderly patients, with a good OS without severe side effects. Higher GPA score and active systemic treatment were associated with improved OS, indicating that elderly patients are significant candidates for SRS/FSRT.

997 View
85 Download

Prognostic Evaluation and Survival Prediction for Combined Hepatocellular-Cholangiocarcinoma Following Hepatectomy: Seok-Joo Chun, Yu Jung Jung, YoungRok Choi, Nam-Joon Yi, Kwang-Woong Lee, Kyung-Suk Suh, Kyoung Bun Lee, Hyun-Cheol Kang, Eui Kyu Chie, Kyung Su Kim; Received February 19, 2024 Accepted June 26, 2024 Published online July 3, 2024; DOI: https://doi.org/10.4143/crt.2024.176 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study aimed to assess prognostic factors associated with combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and to predict 5-year survival based on these factors.
Materials and Methods
Patients who underwent definitive hepatectomy from 2006 to 2022 at a single institution was retrospectively analyzed. Inclusion criteria involved a pathologically confirmed diagnosis of cHCC-CCA.
Results
A total of 80 patients with diagnosed cHCC-CCA were included in the analysis. The median progression-free survival was 15.6 months, while distant metastasis-free survival (DMFS), hepatic progression-free survival, and overall survival (OS) were 50.8, 21.5, and 85.1 months, respectively. In 52 cases of recurrence, intrahepatic recurrence was the most common initial recurrence (34/52), with distant metastasis in 17 cases. Factors associated with poor DMFS included tumor necrosis, lymphovascular invasion (LVI), perineural invasion, and histologic compact type. Postoperative carbohydrate antigen 19-9, tumor necrosis, LVI, and close/positive margin were associated with poor OS. LVI emerged as a key factor affecting both DMFS and OS, with a 5-year OS of 93.3% for patients without LVI compared to 35.8% with LVI. Based on these factors, a nomogram predicting 3-year and 5-year DMFS and OS was developed, demonstrating high concordance with actual survival in the cohort (Harrell C-index 0.809 for OS, 0.801 for DMFS, respectively).
Conclusion
The prognosis of cHCC-CCA is notably poor when combined with LVI. Given the significant impact of adverse features, accurate outcome prediction is crucial. Moreover, consideration of adjuvant therapy may be warranted for patients exhibiting poor survival and increased risk of local recurrence or distant metastasis.

1,021 View
53 Download

Gastrointestinal cancer

Distinct Characteristics and Changes in Liver Function of Patients with Hepatocellular Carcinoma Treated with Atezolizumab Plus Bevacizumab for More Than 1 Year: Youngun Kim, Jung Sun Kim, Beodeul Kang, Ilhwan Kim, Hyeyeong Kim, Won Suk Lee, Yun Beom Sang, Sanghoon Jung, Chansik An, Chan Kim, Hong Jae Chon; Cancer Res Treat. 2024;56(4):1231-1239. Published online May 27, 2024; DOI: https://doi.org/10.4143/crt.2024.237

Abstract PDF Supplementary Material PubReader ePub: Purpose
Since 2020, atezolizumab plus bevacizumab (Ate/Bev) has been the standard first-line therapy for unresectable hepatocellular carcinoma (HCC), but long-term treatment studies are limited. This study evaluated the clinical characteristics and effects of Ate/Bev for over 1 year.
Materials and Methods
This study included patients with unresectable HCC treated with first-line Ate/Bev between May 2020 and April 2022. Those receiving Ate/Bev for 1 year or more were classified as the long-term treatment group.
Results
Of 246 patients, 69 (28.0%) were in the long-term treatment group, which comprised more proportions of intrahepatic tumor burden < 25%, Eastern Cooperative Oncology Group 0, and a lower proportion of portal vein tumor thrombosis than the short-term treatment group. The long-term treatment group had a higher incidence of atezolizumab-related thyroid dysfunction (31.9% vs. 10.7%, p < 0.001; median time to onset [mTTO], 2.8 months), dermatologic toxicity (29.0% vs. 14.7%, p=0.017; mTTO, 3.3 months), bevacizumab-related hypertension (44.9% vs. 22.0%, p=0.001; mTTO, 4.2 months), and proteinuria (69.6% vs. 38.4%, p < 0.001; mTTO, 6.8 months), compared to the short-term treatment group. Regarding liver function in the long-term treatment group, patients initially classified as Child-Pugh class A decreased from 87.0% to 75.4%, and albumin-bilirubin grade 1 decreased from 68.1% to 50.7% after 1 year of treatment.
Conclusion
The Ate/Bev long-term treatment group had a lower intrahepatic tumor burden, less portal vein tumor thrombosis, and better performance status and liver function at baseline. Atezolizumab-related immunological adverse events emerged relatively early in treatment compared to the bevacizumab-related. Additionally, some patients demonstrated liver function deterioration during long-term Ate/Bev treatment.

1,496 View
117 Download

Clinical and Radiologic Predictors of Response to Atezolizumab-Bevacizumab in Advanced Hepatocellular Carcinoma: Se Jin Choi, Sung Won Chung, Jonggi Choi, Kang Mo Kim, Hyung-Don Kim, Changhoon Yoo, Baek-Yeol Ryoo, Seung Soo Lee, Won-Mook Choi, Sang Hyun Choi; Cancer Res Treat. 2024;56(4):1219-1230. Published online May 7, 2024; DOI: https://doi.org/10.4143/crt.2024.283

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to identify clinical and radiologic characteristics that could predict response to atezolizumab-bevacizumab combination therapy in patients with advanced hepatocellular carcinoma (HCC).
Materials and Methods
This single-center retrospective study included 108 advanced HCC patients with intrahepatic lesions who were treated with atezolizumab-bevacizumab. Two radiologists independently analyzed imaging characteristics of the index tumor on pretreatment computed tomography. Predictive factors associated with progressive disease (PD) at the best response based on Response Evaluation Criteria in Solid Tumors, ver. 1.1 were evaluated using logistic regression analysis. Progression-free survival (PFS) was estimated by the Kaplan-Meier method and compared with the log-rank test.
Results
Of 108 patients with a median PFS of 15 weeks, 40 (37.0%) had PD during treatment. Factors associated with PD included the presence of extrahepatic metastases (adjusted odds ratio [aOR], 4.13; 95% confidence interval [CI], 1.19 to 14.35; p=0.03), the infiltrative appearance of the tumor (aOR, 3.07; 95% CI, 1.05 to 8.93; p=0.04), and the absence of arterial-phase hyperenhancement (APHE) (aOR, 6.34; 95% CI, 2.18 to 18.47; p < 0.001). Patients with two or more of these factors had a PD of 66.7% and a median PFS of 8 weeks, indicating a significantly worse outcome compared to the patients with one or no of these factors.
Conclusion
In patients with advanced HCC treated with atezolizumab-bevacizumab treatment, the absence of APHE, infiltrative appearance of the intrahepatic tumor, and presence of extrahepatic metastases were associated with poor response and survival. Evaluation of early response may be necessary in patients with these factors.

Citations

Citations to this article as recorded by

Liver Transplantation for Hepatocarcinoma: Results over Two Decades of a Transplantation Programme and Analysis of Factors Associated with Recurrence
María Martínez Burgos, Rocío González Grande, Susana López Ortega, Inmaculada Santaella Leiva, Jesús de la Cruz Lombardo, Julio Santoyo Santoyo, Miguel Jiménez Pérez
Biomedicines.2024; 12(6): 1302. CrossRef

1,397 View
93 Download
1 Web of Science
1 Crossref

Lung and Thoracic cancer

Adjuvant Pembrolizumab in Patients with Stage IIIA/N2 Non–Small Cell Lung Cancer Completely Resected after Neoadjuvant Concurrent Chemoradiation: A Prospective, Open-Label, Single-Arm, Phase 2 Trial: Junghoon Shin, Sehhoon Park, Kyung Hwan Kim, Eui-Cheol Shin, Hyun Ae Jung, Jong Ho Cho, Jong-Mu Sun, Se-Hoon Lee, Yong Soo Choi, Jin Seok Ahn, Jhingook Kim, Keunchil Park, Young Mog Shim, Hong Kwan Kim, Jae Myoung Noh, Yong Chan Ahn, Hongryull Pyo, Myung-Ju Ahn; Cancer Res Treat. 2024;56(4):1084-1095. Published online April 30, 2024; DOI: https://doi.org/10.4143/crt.2024.084

Abstract PDF Supplementary Material PubReader ePub: Purpose
Optimal treatment for stage IIIA/N2 non–small cell lung cancer (NSCLC) is controversial. We aimed to assess the efficacy and safety of adjuvant pembrolizumab for stage IIIA/N2 NSCLC completely resected after neoadjuvant concurrent chemoradiation therapy (CCRT).
Materials and Methods
In this open-label, single-center, single-arm phase 2 trial, patients with stage IIIA/N2 NSCLC received adjuvant pembrolizumab for up to 2 years after complete resection following neoadjuvant CCRT. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and safety. As an exploratory biomarker analysis, we evaluated the proliferative response of blood CD39⁺PD-1⁺CD8⁺ T cells using fold changes in the percentage of proliferating Ki-67⁺ cells from days 1 to 7 of cycle 1 (Ki-67_D7/D1).
Results
Between October 2017 and October 2018, 37 patients were enrolled. Twelve (32%) and three (8%) patients harbored EGFR and ALK alterations, respectively. Of 34 patients with programmed cell death ligand 1 assessment, 21 (62%), nine (26%), and four (12%) had a tumor proportion score of < 1%, 1%-50%, and ≥ 50%, respectively. The median follow-up was 71 months. The median DFS was 22.4 months in the overall population, with a 5-year DFS rate of 29%. The OS rate was 86% at 2 years and 76% at 5 years. Patients with tumor recurrence within 6 months had a significantly lower Ki-67D7/D1 among CD39⁺PD-1⁺CD8⁺ T cells than those without (p=0.036). No new safety signals were identified.
Conclusion
Adjuvant pembrolizumab may offer durable disease control in a subset of stage IIIA/N2 NSCLC patients after neoadjuvant CCRT and surgery.

1,792 View
124 Download

Gastrointestinal cancer

Efficacy of Lenvatinib Combined with Anti–PD-1 Antibodies Plus Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Retrospective, Multicenter Study: Xiangye Ou, Junyi Wu, Jiayi Wu, Yangkai Fu, Zhenxin Zeng, Shuqun Li, Yinan Li, Deyi Liu, Han Li, Bin Li, Jianyin Zhou, Shaowu Zhuang, Shuqun Cheng, Zhibo Zhang, Kai Wang, Shuang Qu, Maolin Yan; Cancer Res Treat. 2024;56(4):1207-1218. Published online April 30, 2024; DOI: https://doi.org/10.4143/crt.2023.1165

Abstract PDF Supplementary Material PubReader ePub: Purpose
The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) is extremely poor, and systemic therapy is currently the mainstream treatment. This study aimed to assess the efficacy and safety of lenvatinib combined with anti–programmed cell death-1 antibodies and transcatheter arterial chemoembolization (triple therapy) in patients with HCC and PVTT.
Materials and Methods
This retrospective multicenter study included patients with HCC and PVTT who received triple therapy, were aged between 18 and 75 years, classified as Child-Pugh class A or B, and had at least one measurable lesion. The overall survival (OS), progression-free survival (PFS), objective response rates, and disease control rates were analyzed to assess efficacy. Treatment-related adverse events were analyzed to assess safety profiles.
Results
During a median follow-up of 11.23 months (range, 3.07 to 34.37 months), the median OS was greater than 24 months, and median PFS was 12.53 months. The 2-year OS rate was 54.9%. The objective response rate and disease control rate were 69.8% (74/106) and 84.0% (89/106), respectively; 20.8% (22/106) of the patients experienced grade 3/4 treatment-related adverse events and no treatment-related deaths occurred. The conversion rate to liver resection was 31.1% (33/106), with manageable postoperative complications. The median OS was not reached in the surgery group, but was 19.08 months in the non-surgery group. The median PFS in the surgery and non-surgery groups were 20.50 and 9.00 months, respectively.
Conclusion
Triple therapy showed promising survival benefits and high response rates in patients with HCC and PVTT, with manageable adverse effects.

1,516 View
104 Download

Head and Neck cancer

The Impact of Infectious Mononucleosis History on the Risk of Developing Lymphoma and Nasopharyngeal Carcinoma: A Retrospective Large-Scale Cohort Study Using National Health Insurance Data in South Korea: So Hee Kang, Yun-Hee Lee, Jun-Pyo Myong, Minsu Kwon; Cancer Res Treat. 2024;56(4):1077-1083. Published online April 23, 2024; DOI: https://doi.org/10.4143/crt.2023.1356

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study aimed to assess the long-term risks associated with a history of infectious mononucleosis (IM), primarily caused by the Epstein-Barr virus (EBV). Specifically analyzing the potential increase in developing nasopharyngeal cancer (NPC) and lymphoma in patients with a history of IM and exploring the prevalence of other EBV-associated conditions.
Materials and Methods
The Korean National Health Insurance Service (NHIS) database was utilized for a retrospective analysis, covering data from 2002 to 2021. A total of 25,582 IM patients and controls were included, with 1:1 propensity score matching. The study monitored outcomes, including lymphoma, NPC, gastric cancer, multiple sclerosis, and all-cause mortality.
Results
Patients with a history of IM demonstrated a significantly higher incidence of lymphoma (hazard ratio [HR], 5.320; 95% confidence interval [CI], 3.208 to 8.820; p < 0.001) and NPC (HR, 7.116; 95% CI, 1.617 to 31.314; p=0.009) during the follow-up period compared with the control group. Additionally, the IM group showed an increased rate of all-cause mortality (HR, 2.225; 95% CI, 1.858 to 2.663; p < 0.001).
Conclusion
This study suggests that individuals with a history of IM have an elevated risk of developing lymphoma and NPC in South Korea, emphasizing the importance of vigilant follow-up and monitoring. The results advocate for heightened awareness and potential national monitoring policies to address the long-term health implications of EBV infection and to implement preventive measures.

1,196 View
108 Download

Analysis of Response and Progression Patterns of Tyrosine Kinase Inhibitors in Recurrent or Metastatic Adenoid Cystic Carcinoma: A Post Hoc Analysis of Two KCSG Phase II Trials: Youjin Kim, Bhumsuk Keam, Eun Joo Kang, Jin-Soo Kim, Hye Ryun Kim, Keun-Wook Lee, Jung Hye Kwon, Kyoung Eun Lee, Yaewon Yang, Yoon Hee Choi, Min Kyoung Kim, Jun Ho Ji, Tak Yun, Moon Young Choi, Ki Hyeong Lee, Sung-Bae Kim, Myung-Ju Ahn; Cancer Res Treat. 2024;56(4):1068-1076. Published online April 15, 2024; DOI: https://doi.org/10.4143/crt.2024.008

Abstract PDF Supplementary Material PubReader ePub: Purpose
In this study, we evaluated 66 patients diagnosed with adenoid cystic carcinoma (ACC) enrolled in two Korean Cancer Study Group trials to investigate the response and progression patterns in recurrent and/or metastatic ACC treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs).
Materials and Methods
We evaluated 66 patients diagnosed with ACC who were enrolled in the Korean Cancer Study Group trials. The tumor measurements, clinical data, treatment outcomes, and progression patterns of therapy were analyzed.
Results
In the 66 patients (53 receiving axitinib and 13 receiving nintedanib), the disease control rate was 61%, and three patients achieved partial response. The median follow-up, median progression-free survival (PFS), overall survival, and 6-month PFS rate were 27.6%, 12.4%, and 18.1% months and 62.1%, respectively. Among 42 patients who experienced progression, 27 (64.3%) showed target lesion progression. Bone metastasis was an independent poor prognostic factor.
Conclusion
Overall, most patients demonstrated stable disease with prolonged PFS; however, prominent target lesion progression occurred in some patients. Thus, PFS may capture VEGFR-TKI efficacy better than the objective response rate.

1,504 View
114 Download

Metronomic S-1 Adjuvant Chemotherapy Improves Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma: Yi-Feng Yu, Peng Wu, Rui Zhuo, San-Gang Wu; Cancer Res Treat. 2024;56(4):1058-1067. Published online February 19, 2024; DOI: https://doi.org/10.4143/crt.2023.1343

Abstract PDF PubReader ePub

Purpose
This study aimed to investigate the efficacy and safety of using metronomic S-1 adjuvant chemotherapy in locoregionally advanced nasopharyngeal carcinoma (LANPC).
Materials and Methods
We retrospectively collected data on patients diagnosed with LANPC between January 2016 and December 2021. All patients were treated with induction chemotherapy and concurrent chemoradiotherapy with or without metronomic chemotherapy (MC). Toxicities during MC were recorded. The chi-square test, Kaplan-Meier methods, propensity score matching (PSM), and Cox proportional hazards model were used for statistical analyses.
Results
A total of 474 patients were identified, including 64 (13.5%) and 410 (83.5%) patients with or without receiving MC, respectively. Patients who received metronomic S-1 had significantly better 3-year locoregional recurrence-free survival (LRFS) (100% vs. 90.9%, p=0.038), distant metastasis-free survival (DMFS) (98.5% vs. 84.1%, p=0.002), disease-free survival (DFS) (98.4% vs. 77.5%, p < 0.001), and overall survival (OS) (98.0% vs. 87.7%, p=0.008) compared to those without metronomic S-1. The multivariate prognostic analysis revealed that metronomic S-1 was identified as an independent prognostic factor associated with better DMFS (hazard ratio [HR], 0.074; p=0.010), DFS (HR, 0.103; p=0.002) and OS (HR, 0.127; p=0.042), but not in LRFS (p=0.071). Similar results were found using PSM. Common adverse events observed in the metronomic S-1 group included leukopenia, neutropenia, increased total bilirubin, anorexia, rash/desquamation, and hyperpigmentation. All patients with adverse events were grade 1-2.
Conclusion
It is worth conducting a randomized controlled trial to assess the effect of metronomic S-1 on survival outcomes and toxicities of LANPC.

Citations

Citations to this article as recorded by

Short-term versus long-term metronomic adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma: A propensity score-matched real-world study
Shuhui Dong, Weixin Bei, Lanfeng Lin, Yaofei Jiang, Nian Lu, Guoying Liu, Yanqun Xiang, Weixiong Xia
Oral Oncology.2024; 156: 106908. CrossRef

1,456 View
100 Download
1 Web of Science
1 Crossref

Gastrointestinal cancer

Global Expanded Access Program for Pemigatinib in Patients with Previously Treated Locally Advanced or Metastatic Cholangiocarcinoma and Fibroblast Growth Factor Receptor Gene Alterations: Anouk Lindley, Gerald Prager, Michael Bitzer, Timothy C. Burn, Christine F. Lihou, Elisabeth Croft; Cancer Res Treat. 2024;56(3):847-855. Published online February 7, 2024; DOI: https://doi.org/10.4143/crt.2023.1197

Abstract PDF Supplementary Material PubReader ePub

Purpose
Pemigatinib is a fibroblast growth factor receptor-2 (FGFR2) inhibitor approved for use in patients with previously treated cholangiocarcinoma (CCA) and FGFR2 fusions or rearrangements. This ongoing global Expanded Access Program (EAP) allows physicians in regions where pemigatinib is not commercially available to request pemigatinib for patients with locally advanced or metastatic CCA who, in the physician’s opinion, could benefit from pemigatinib treatment.
Materials and Methods
Eighty-nine patients from Europe, North America, and Israel were treated from January 2020 through September 2021.
Results
Patients had FGFR gene fusions (68.5%), rearrangements (12.4%), translocations (5.6%), amplifications (2.2%), and other alterations (11.2%). Median duration of treatment in the EAP was 4.0 months (range, 0.1 to 13.6 months). The most frequently reported adverse event (AE) was hyperphosphatemia (22.5%); the most common serious AE was cholangitis (3.4%). Treatment discontinuation was associated with reports of AEs for seven patients (7.9%). AEs associated with pemigatinib were consistent with those observed in clinical trials.
Conclusion
Efficacy was not assessed in this EAP. However, some patients remained on treatment for up to a year, suggesting that they observed a benefit from treatment. Patients with CCA should undergo molecular testing to identify those who could benefit from targeted treatments such as pemigatinib.

Citations

Citations to this article as recorded by

Precision oncology targeting FGFRs: A systematic review on pre-clinical activity and clinical outcomes of pemigatinib
Ludovica Gnagni, Ilary Ruscito, Ilaria Grazia Zizzari, Marianna Nuti, Chiara Napoletano, Aurelia Rughetti
Critical Reviews in Oncology/Hematology.2024; 202: 104464. CrossRef

2,550 View
196 Download
1 Web of Science
1 Crossref

Lung and Thoracic cancer

Comparison of Clinicopathogenomic Features and Treatment Outcomes of EGFR and HER2 Exon 20 Insertion Mutations in Non–Small Cell Lung Cancer: Single-Institution Experience: So Heun Lee, Hyehyun Jeong, Deok Hoon Kim, Se Jin Jang, Sang-We Kim, Shinkyo Yoon, Dae Ho Lee; Cancer Res Treat. 2024;56(3):774-784. Published online January 30, 2024; DOI: https://doi.org/10.4143/crt.2023.1177

Abstract PDF PubReader ePub: Purpose
Exon 20 insertion mutations (E20ins) in epidermal growth factor receptor (EGFR) or human epidermal growth factor receptor 2 (HER2) in non–small cell lung cancer (NSCLC) patients has become more important with emergence of novel agents targeting E20ins.
Materials and Methods
Advanced/Metastatic NSCLC patients with E20ins were included. EGFR E20ins was identified by two methods, next-generation sequencing (NGS) or real-time polymerase chain reaction (PCR), while HER2 E20ins was done by NGS only.
Results
Between December 2013 and July 2021, E20ins were identified in 107 patients at Asan Medical Center; 67 EGFR E20ins and 40 HER2 E20ins. Out of 32 patients with EGFR E20ins who had tested both PCR and NGS, 17 were identified only through NGS and the other 15 through both tests, giving a discordance rate of 53.1%. There was no clinically significant difference in clinicopathologic features between EGFR and HER2 E20ins; both were observed more frequently in adenocarcinoma, female and never-smokers. Brain metastases were evident at diagnosis in 31.8% of EGFR E20ins and 27.5% of HER2 E20ins, respectively. Platinum-based doublets demonstrated objective response rates (ORR) of 13.3% with a median progression-free survival (PFS) of 4.2 months for EGFR E20ins and 35.3% with 4.7 months for HER2 E20ins, respectively. In contrast, novel EGFR E20ins-targeted agents exhibited an ORR of 46.2% with a median PFS of 5.4 months, while HER2-targeted agents showed an ORR of 50% with that of 7.0 months.
Conclusion
Identification of EGFR and HER2 E20ins is more important as their targeted therapies improved outcomes. Upfront NGS test as a comprehensive molecular approach is strongly warranted.

2,523 View
162 Download

Genitourinary cancer

Adjuvant Chemotherapy for Upper Tract Urothelial Carcinoma: A Real-World, Retrospective Study: Junho Lee, Sung Hee Lim, Jae Hoon Chung, Wan Song, Hyun Hwan Sung, Byong Chang Jeong, Se Hoon Park; Cancer Res Treat. 2024;56(3):871-876. Published online January 16, 2024; DOI: https://doi.org/10.4143/crt.2023.1226

Abstract PDF PubReader ePub

Purpose
The aim of this retrospective study was to evaluate the efficacy of adjuvant cisplatin-based chemotherapy in patients with locally advanced upper tract urothelial carcinoma (UTUC), administered following radical nephroureterectomy.
Materials and Methods
Patients with UTUC, arising from renal pelvis or ureter, staged pT3/T4 or N+ were treated with adjuvant chemotherapy following surgery. The chemotherapy consisted of gemcitabine 1,000 mg/m² on days 1 and 8, cisplatin 70 mg/m² on day 1. Treatment was repeated every 3 weeks for up to 4 cycles. Endpoints included disease-free survival (DFS), metastasis-free survival (MFS), and safety.
Results
Among 89 eligible patients, 85 (95.5%) completed at least 3 cycles of adjuvant chemotherapy. Chemotherapy was well tolerated, the main toxicities being mild-to-moderate gastrointestinal toxic effects and pruritus. With a median follow-up of 37 months, median DFS was 30 months (95% confidence interval, 22 to 39), and the median MFS was not reached. The 3-year DFS and MFS were 44% and 56%, respectively. Multivariate analyses revealed that the main factor associated with DFS and MFS was the lymph node involvement, whereas age, T category, grade, or the primary site of UTUC were not significantly associated with DFS or MFS.
Conclusion
Adjuvant cisplatin-based chemotherapy after radical surgery of pT3/T4 or N+ UTUC was feasible and may demonstrate benefits in DFS and MFS. Whether novel agents added to the chemotherapy regimen, as a concurrent combination or maintenance, impacts on survival or reduces the development of metastases remains to be studied.

Citations

Citations to this article as recorded by

Cisplatin/gemcitabine

Reactions Weekly.2024; 2027(1): 127. CrossRef

2,382 View
112 Download
1 Crossref

Lung and Thoracic cancer

Contribution of Enhanced Locoregional Control to Improved Overall Survival with Consolidative Durvalumab after Concurrent Chemoradiotherapy in Locally Advanced Non–Small Cell Lung Cancer: Insights from Real-World Data: Jeong Yun Jang, Si Yeol Song, Young Seob Shin, Ha Un Kim, Eun Kyung Choi, Sang-We Kim, Jae Cheol Lee, Dae Ho Lee, Chang-Min Choi, Shinkyo Yoon, Su Ssan Kim; Cancer Res Treat. 2024;56(3):785-794. Published online January 16, 2024; DOI: https://doi.org/10.4143/crt.2023.1014

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to assess the real-world clinical outcomes of consolidative durvalumab in patients with unresectable locally advanced non–small cell lung cancer (LA-NSCLC) and to explore the role of radiotherapy in the era of immunotherapy.
Materials and Methods
This retrospective study assessed 171 patients with unresectable LA-NSCLC who underwent concurrent chemoradiotherapy (CCRT) with or without consolidative durvalumab at Asan Medical Center between May 2018 and May 2021. Primary outcomes included freedom from locoregional failure (FFLRF), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS).
Results
Durvalumab following CCRT demonstrated a prolonged median PFS of 20.9 months (p=0.048) and a 3-year FFLRF rate of 57.3% (p=0.008), compared to 13.7 months and 38.8%, respectively, with CCRT alone. Furthermore, the incidence of in-field recurrence was significantly greater in the CCRT-alone group compared to the durvalumab group (26.8% vs. 12.4%, p=0.027). While median OS was not reached with durvalumab, it was 35.4 months in patients receiving CCRT alone (p=0.010). Patients positive for programmed cell death ligand 1 (PD-L1) expression showed notably better outcomes, including FFLRF, DMFS, PFS, and OS. Adherence to PACIFIC trial eligibility criteria identified 100 patients (58.5%) as ineligible. The use of durvalumab demonstrated better survival regardless of eligibility criteria.
Conclusion
The use of durvalumab consolidation following CCRT significantly enhanced locoregional control and OS in patients with unresectable LA-NSCLC, especially in those with PD-L1–positive tumors, thereby validating the role of durvalumab in standard care.

Citations

Citations to this article as recorded by

Therapeutic effect of induction therapy including nab-paclitaxel followed by surgical resection for the patients with locally advanced non-small-cell lung cancer
Hidetaka Uramoto, Nozomu Motono, Shun Iwai
Journal of Cardiothoracic Surgery.2024;[Epub] CrossRef

3,001 View
145 Download
1 Web of Science
1 Crossref

Analytical and Clinical Validation of a Highly Sensitive NGS-Based ctDNA Assay with Real-World Concordance in Non–Small Cell Lung Cancer: Hanbaek Yi, Jeonghwan Youk, Yoojoo Lim, Hanseong Roh, Dongsoo Kyung, Hwang-Phill Kim, Duhee Bang, Bhumsuk Keam, Tae-Min Kim, Miso Kim, Dong-Wan Kim, Tae-You Kim; Cancer Res Treat. 2024;56(3):765-773. Published online January 8, 2024; DOI: https://doi.org/10.4143/crt.2023.1294

Abstract PDF Supplementary Material PubReader ePub

Purpose
There have been needs to improve the sensitivity of liquid biopsy. This report aims to report the analytical and clinical validation of a next-generation sequencing (NGS)–based circulating tumor DNA (ctDNA) assay.
Materials and Methods
Analytical validation was conducted in vitro by evaluating the limit of detection (LOD), precision, and specificity for various genomic aberrations. The real-world performance in non–small cell lung cancer (NSCLC) was assessed by comparing the results of AlphaLiquid100 to the tissue-based results.
Results
The LODs with 30 ng input DNA were 0.11%, 0.11%, 0.06%, 0.21%, and 2.13 copies for detecting single nucleotide variants, insertions, deletions, fusions, and copy number alterations (CNA), respectively. Quantitatively, single nucleotide variants/insertions and deletions, fusions, and CNAs showed a good correlation (R²=0.91, 0.40, and 0.65; y=0.95, 1.06, and 1.19) to the manufacturer’s values, and per-base specificities for all types of variants were near 100%. In real-world NSCLC (n=122), key actionable mutations in NSCLC were detected in 60.7% (74/122) with the ctDNA assay. Comparative analysis against the NGS-based tissue results for all key mutations showed positive percent agreement (PPA) of 85.3%. For individual genes, the PPA was as high as 95.7% for epidermal growth factor receptor (EGFR) mutations and 83.3% for ALK translocations. AlphaLiquid100 detected drug-sensitive EGFR mutation at a variant allele frequency as low as 0.02% and also identified an EGFR mutation in a case where tissue sample missed. Blood samples collected post-targeted therapies revealed additional acquired mutations.
Conclusion
The AlphaLiquid100 ctDNA assay demonstrates robust analytical validity, offering clinically important information for NSCLC patients.

Citations

Citations to this article as recorded by

Next-generation sequencing impact on cancer care: applications, challenges, and future directions
Mariano Zalis, Gilson Gabriel Viana Veloso, Pedro Nazareth Aguiar Jr., Nathalia Gimenes, Marina Xavier Reis, Silvio Matsas, Carlos Gil Ferreira
Frontiers in Genetics.2024;[Epub] CrossRef
Profiling Cell-Free DNA from Malignant Pleural Effusion for Oncogenic Driver Mutations in Patients with Treatment-Naive Stage IV Adenocarcinoma: A Multicenter Prospective Study
Shih-Chieh Chang, Yu-Feng Wei, Chung-Yu Chen, Yi-Chun Lai, Po-Wei Hu, Jui-Chi Hung, Cheng-Yu Chang
Molecular Diagnosis & Therapy.2024; 28(6): 803. CrossRef
Concordance of ctDNA and tissue genomic profiling in advanced biliary tract cancer
Sohyun Hwang, Seonjeong Woo, Beodeul Kang, Haeyoun Kang, Jung Sun Kim, Sung Hwan Lee, Chang Il Kwon, Dong Soo Kyung, Hwang-Phill Kim, Gwangil Kim, Chan Kim, Hong Jae Chon
Journal of Hepatology.2024;[Epub] CrossRef

4,555 View
332 Download
2 Web of Science
3 Crossref

Gastrointestinal cancer

Combined High-Dose Radiotherapy with Sequential Gemcitabine-Cisplatin Based Chemotherapy Increase the Resectability and Survival in Locally Advanced Unresectable Intrahepatic Cholangiocarcinoma: A Multi-institutional Cohort Study: Jung Ho Im, Jeong Il Yu, Tae Hyun Kim, Tae Gyu Kim, Jun Won Kim, Jinsil Seong; Cancer Res Treat. 2024;56(3):838-846. Published online January 2, 2024; DOI: https://doi.org/10.4143/crt.2023.886

Abstract PDF Supplementary Material PubReader ePub: Purpose
The locally advanced unresectable intrahepatic cholangiocarcinoma (ICC) has detrimental oncological outcomes. In this study, we aimed to investigate the efficacy of radiotherapy in patients with locally advanced unresectable ICC.
Materials and Methods
Between 2001 and 2021, 116 patients were identified through medical record who underwent radiotherapy for locally advanced unresectable ICC. The resectability of ICC is determined by the multidisciplinary team at each institution. Overall survival (OS) were analyzed using the Kaplan-Meier method, and prognostic factors were analyzed using the Cox proportional hazards model.
Results
The median equivalent radiotherapy dose in 2 Gy fractions (EQD2) was 52 Gy (range, 30 to 110 Gy). Forty-seven patients (40.5%) received sequential gemcitabine-cisplatin based chemotherapy (GEM-CIS CTx). Multivariate analysis identified two risk factors, EQD2 of ≥ 60 Gy and application of sequential GEM-CIS CTx for OS. Patients were grouped by these two risk factors: group 1, EQD2 ≥ 60 Gy with sequential GEM-CIS CTx (n=25); group 2, EQD2 < 60 Gy with sequential GEM-CIS CTx or fluoropyrimidine-based concurrent chemoradiotherapy (n=70); and group 3, radiotherapy alone (n=21). Curative resection was more frequently undergone in group 1 than in groups 2 or 3 (28% vs. 8.6% vs. 0%, respectively). Consequently, OS was significantly better in group 1 than in groups 2 and 3 (p < 0.05).
Conclusion
Combined high-dose radiotherapy with sequential GEM-CIS CTx improved oncologic outcomes in patients with locally advanced unresectable ICC. Further prospective studies are required to validate these findings.

2,663 View
130 Download

Genitourinary cancer

Invasiveness of Upper Tract Urothelial Carcinoma: Clinical Significance and Integrative Diagnostic Strategy: Bokyung Ahn, Doeun Kim, Kye Jin Park, Ja-Min Park, Sun Young Yoon, Bumsik Hong, Yong Mee Cho, Deokhoon Kim; Cancer Res Treat. 2024;56(3):856-870. Published online December 18, 2023; DOI: https://doi.org/10.4143/crt.2023.1150

Abstract PDF Supplementary Material PubReader ePub

Purpose
In this study, we aimed to determine the clinicopathologic, radiologic, and molecular significance of the tumor invasiveness to further stratify the patients with high-grade (HG) upper tract urothelial carcinoma (UTUC) who can be treated less aggressively.
Materials and Methods
Clinicopathologic and radiologic characteristics of 166 surgically resected HG UTUC (48 noninvasive, and 118 invasive) cases were evaluated. Six noninvasive UTUC cases with intratumoral tumor grade heterogeneity were selected for whole-exome sequencing (WES) to understand the underlying molecular pathophysiology. Barcode-tagging sequencing was done for validation of the target genes from WES data.
Results
Patients with noninvasive UTUC showed no cancer-specific death with better cancer-specific survival (p < 0.001) and recurrence-free survival (p < 0.001) compared to the patients with invasive UTUC. Compared to the invasive UTUC, noninvasive UTUC was correlated to a low grade (LG) on the preoperative abdominal computed tomography (CT) grading system (p < 0.001), histologic intratumoral tumor grade heterogeneity (p=0.018), discrepancy in preoperative urine cytology diagnosis (p=0.018), and absence of urothelial carcinoma in situ (p < 0.001). WES of the heterogeneous components showed mutually shared HRAS and FGFR3 mutations shared between the HG and LG components. HRAS mutation was associated with the lower grade on preoperative abdominal CT and intratumoral tumor grade heterogeneity (p=0.045 and p < 0.001, respectively), whereas FGFR3 mutation was correlated to the absence of carcinoma in situ (p < 0.001).
Conclusion
According to our comprehensive analysis, HG noninvasive UTUC can be preoperatively suspected based on distinct preoperative radiologic, cytologic, histologic, and molecular features. Noninvasive HG UTUC shows excellent prognosis and thus should be treated less aggressively.

Citations

Citations to this article as recorded by

Diagnostic accuracy of upper tract urothelial carcinoma using biopsy, urinary cytology, and nephroureterectomy specimens: A tertiary cancer center experience
Jianping Zhao, Yuan Shen, Ming Guo, Surena F Matin, Donna E Hansel, Charles C Guo
American Journal of Clinical Pathology.2024;[Epub] CrossRef
Clinical significance of tumor location for ureteroscopic tumor grading in upper tract urothelial carcinoma
Satoshi Katayama, benjamin pradere, Nico C. Grossmann, Aaron M. Potretzke, Stephen J Boorjian, Alireza Ghoreifi, Siamak Daneshmand, Hooman Djaladat, John Sfakianos, Andrea Mari, Zine-Eddine Khene, David D'Andrea, Nozomi Hayakawa, Kazutoshi Fujita, Axel He
Journal of Endourology.2024;[Epub] CrossRef

2,568 View
110 Download
2 Web of Science
2 Crossref

Lung and Thoracic cancer

Clinical Effect of Endosonography on Overall Survival in Patients with Radiological N1 Non–Small Cell Lung Cancer: Bo-Guen Kim, Byeong-Ho Jeong, Goeun Park, Hong Kwan Kim, Young Mog Shim, Sun Hye Shin, Kyungjong Lee, Sang-Won Um, Hojoong Kim, Jong Ho Cho; Cancer Res Treat. 2024;56(2):502-512. Published online December 4, 2023; DOI: https://doi.org/10.4143/crt.2023.840

Abstract PDF Supplementary Material PubReader ePub: Purpose
It is unclear whether performing endosonography first in non–small cell lung cancer (NSCLC) patients with radiological N1 (rN1) has any advantages over surgery without nodal staging. We aimed to compare surgery without endosonography to performing endosonography first in rN1 on the overall survival (OS) of patients with NSCLC.
Materials and Methods
This is a retrospective analysis of patients with rN1 NSCLC between 2013 and 2019. Patients were divided into ‘no endosonography’ and ‘endosonography first’ groups. We investigated the effect of nodal staging through endosonography on OS using propensity score matching (PSM) and multivariable Cox proportional hazard regression analysis.
Results
In the no endosonography group, pathologic N2 occurred in 23.0% of patients. In the endosonography first group, endosonographic N2 and N3 occurred in 8.6% and 1.6% of patients, respectively. Additionally, 51 patients were pathologic N2 among 249 patients who underwent surgery and mediastinal lymph node dissection (MLND) in endosonography first group. After PSM, the 5-year OSs were 68.1% and 70.6% in the no endosonography and endosonography first groups, respectively. However, the 5-year OS was 80.2% in the subgroup who underwent surgery and MLND of the endosonography first group. Moreover, in patients receiving surgical resection with MLND, the endosonography first group tended to have a better OS than the no endosonography group in adjusted analysis using various models.
Conclusion
In rN1 NSCLC, preoperative endosonography shows better OS than surgery without endosonography. For patients with rN1 NSCLC who are candidates for surgery, preoperative endosonography may help improve survival through patient selection.

2,782 View
101 Download

Genitourinary cancer

Clinical Outcomes of Small Cell Carcinoma of the Genitourinary Tract and the Prognostic Significance of the Tumor Immune Microenvironment: Jaewon Hyung, Hyung-Don Kim, Gi Hwan Kim, Yong Mee Cho, Yeon-Mi Ryu, Sang-Yeob Kim, Inkeun Park, Shinkyo Yoon, Jae Lyun Lee; Cancer Res Treat. 2024;56(2):624-633. Published online November 29, 2023; DOI: https://doi.org/10.4143/crt.2023.1076

Abstract PDF Supplementary Material PubReader ePub: Purpose
Small cell carcinoma of the genitourinary tract (GU SCC) is a rare disease with a poor prognosis. There are only limited treatment options due to insufficient understanding of the disease. In this study, we analyzed the clinical outcomes of patients with GU SCC and their association with the tumor immune phenotype.
Materials and Methods
Patients diagnosed with GU SCC were included. Survival outcomes according to the primary location (prostate and non-prostate) and stages (limited disease [LD] and extensive disease [ED]) were analyzed. We performed multiplex immunohistochemistry (IHC) in non-prostate SCC patients and analyzed the immune cell population.
Results
A total of 77 patients were included in this study. Their median age was 71 years, 67 patients (87.0%) were male, and 48 patients (62.3%) had non-prostate SCC. All patients with ED (n=31, 40.3%) received etoposide plus platinum (EP) as initial treatment and median overall survival (OS) was 9.7 months (95% confidence interval [CI], 7.1 to 18.6). Patients with LD (n=46, 59.7%) received EP followed by radiotherapy or surgery, and 24-months OS rate was 63.6% (95% CI, 49.9 to 81.0). The multiplex IHC analysis of 21 patients with non-prostate SCC showed that patients with a higher density of programmed death-ligand 1–expressing CD68+CD206+ M2-like macrophages had significantly worse OS outcomes with an adjusted hazards ratio of 4.17 (95% CI, 1.25 to 14.29; adjusted p=0.02).
Conclusion
Patients with GU SCC had a poor prognosis, even those with localized disease. The tumor immune phenotypes were significantly associated with survival. This finding provides new insights for treating GU SCC.

2,924 View
120 Download

Lung and Thoracic cancer

Tissue and Plasma-Based Highly Sensitive Blocker Displacement Amplicon Nanopore Sequencing for EGFR Mutations in Lung Cancer: Patinya Akkhasutthikun, Pornchai Kaewsapsak, Pattaraporn Nimsamer, Pavit Klomkliew, Suthida Visedthorn, Pragwalai Chanchaem, Chinachote Teerapakpinyo, Sunchai Payungporn, Sutima Luangdilok; Cancer Res Treat. 2024;56(2):455-463. Published online November 20, 2023; DOI: https://doi.org/10.4143/crt.2023.1108

Abstract PDF Supplementary Material PubReader ePub

Purpose
The epidermal growth factor receptor (EGFR) mutation is a widely prevalent oncogene driver in non–small cell lung cancer (NSCLC) in East Asia. The detection of EGFR mutations is a standard biomarker test performed routinely in patients with NSCLC for the selection of targeted therapy. Here, our objective was to develop a portable new technique for detecting EGFR (19Del, T790M, and L858R) mutations based on Nanopore sequencing.
Materials and Methods
The assay employed a blocker displacement amplification (BDA)–based polymerase chain reaction (PCR) technique combined with Nanopore sequencing to detect EGFR mutations. Mutant and wild-type EGFR clones were generated from DNA from H1650 (19Del heterozygous) and H1975 (T790M and L858R heterozygous) lung cancer cell lines. Then, they were mixed to assess the performance of this technique for detecting low variant allele frequencies (VAFs). Subsequently, formalin-fixed, paraffin-embedded (FFPE) tissue and cell-free DNA (cfDNA) from patients with NSCLC were used for clinical validation.
Results
The assay can detect low VAF at 0.5% mutant mixed in wild-type EGFR. Using FFPE DNA, the concordance rates of EGFR 19Del, T790M, and L858R mutations between our method and Cobas real-time PCR were 98.46%, 100%, and 100%, respectively. For cfDNA, the concordance rates of EGFR 19Del, T790M, and L858R mutations between our method and droplet digital PCR were 94.74%, 100%, and 100%, respectively.
Conclusion
The BDA amplicon Nanopore sequencing is a highly accurate and sensitive method for the detection of EGFR mutations in clinical specimens.

Citations

Citations to this article as recorded by

Cancer liquid biopsies by Oxford Nanopore Technologies sequencing of cell-free DNA: from basic research to clinical applications
Hua-Qi Si, Peng Wang, Fei Long, Wei Zhong, Yuan-Dong Meng, Yuan Rong, Xiang-Yu Meng, Fu-Bing Wang
Molecular Cancer.2024;[Epub] CrossRef

3,509 View
221 Download
1 Crossref

Genomic Landscape of Pulmonary Sarcomatoid Carcinoma: Hyun Jung Kwon, Sejoon Lee, Yeon Bi Han, Jeonghyo Lee, Soohyeon Kwon, Hyojin Kim, Jin-Haeng Chung; Cancer Res Treat. 2024;56(2):442-454. Published online November 14, 2023; DOI: https://doi.org/10.4143/crt.2023.764

Abstract PDF Supplementary Material PubReader ePub

Purpose
Pulmonary sarcomatoid carcinoma (PSC) is a rare aggressive subtype of non–small cell lung cancer (NSCLC) with limited therapeutic strategies. We attempted to elucidate the evolutionary trajectories of PSC using multiregional and longitudinal tumor samples.
Materials and Methods
A total of 31 patients were enrolled in this study and 11 longitudinal samples were available from them. Using whole exome sequencing data, we analyzed the mutational signatures in both carcinomatous and sarcomatous areas in primary tumors of the 31 patients and longitudinal samples obtained from 11 patients. Furthermore, digital droplet polymerase chain reaction (ddPCR), and programmed death-ligand 1 (PD-L1) immunohistochemistry using the Ventana SP263 assay were performed.
Results
TP53 was identified as the most frequently altered gene in the primary (74%) and metastatic (73%) samples. MET exon 14 skipping mutations, confirmed by ddPCR, and TP53 mutations were mutually exclusive; whereas, MET exon 14 skipping mutations frequently co-occurred with MDM2 amplification. Metastatic tumors showed dissimilar genetic profiles from either primary component. During metastasis, the signatures of APOBEC decreased in metastatic lesions compared with that in primary lesions. PSC showed higher MET and KEAP1 mutations and stronger PD-L1 protein expression compared with that recorded in other NSCLCs.
Conclusion
Decreased APOBEC signatures and subclonal diversity were detected during malignant progression in PSC. Frequent MET mutations and strong PD-L1 expression distinguished PSC from other NSCLCs. The aggressiveness and therapeutic difficulties of PSC were possibly attributable to profound intratumoral and intertumoral genetic diversity. Next-generation sequencing could suggest the appropriate treatment strategy for PSC.

Citations

Citations to this article as recorded by

PD-L1 Expression and Its Modulating Factors in Anaplastic Thyroid Carcinoma
Shipra Agarwal, Chan Kwon Jung, Pranitha Gaddam, Mitsuyoshi Hirokawa, Takuya Higashiyama, Jen-Fan Hang, Wei-An Lai, Somboon Keelawat, Zhiyan Liu, Hee Young Na, So Yeon Park, Junya Fukuoka, Shinya Satoh, Zhanna Mussazhanova, Masahiro Nakashima, Kennichi Ka
American Journal of Surgical Pathology.2024; 48(10): 1233. CrossRef

3,281 View
191 Download
1 Web of Science
1 Crossref

The Real-World Outcome of First Line Atezolizumab in Extensive-Stage Small Cell Lung Cancer: A Multicenter Prospective Cohort Study: Myeong Geun Choi, Yeon Joo Kim, Jae Cheol Lee, Wonjun Ji, In-Jae Oh, Sung Yong Lee, Seong Hoon Yoon, Shin Yup Lee, Jeong Eun Lee, Eun Young Kim, Chang-Min Choi; Cancer Res Treat. 2024;56(2):422-429. Published online October 23, 2023; DOI: https://doi.org/10.4143/crt.2023.913

Abstract PDF Supplementary Material PubReader ePub: Purpose
The addition of immune checkpoint inhibitors to chemotherapy has improved survival outcomes in patients with extensive-stage small cell lung cancer (ES-SCLC). However, their real-world effectiveness remains unknown. Therefore, we investigated the effectiveness of atezolizumab plus chemotherapy in ES-SCLC in actual clinical settings.
Materials and Methods
In this multicenter prospective cohort study, patients with ES-SCLC receiving or scheduled to receive atezolizumab in combination with etoposide and carboplatin were enrolled between June 2021 and August 2022. The primary outcomes were progression-free survival (PFS) and the 1-year overall survival (OS) rate.
Results
A total of 100 patients with ES-SCLC were enrolled from seven centers. Median age was 69 years, and 6% had an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2. The median PFS was 6.0 months, the 1-year OS rate was 62.2%, and the median OS was 13.5 months. An ECOG PS of 2-3 and progressive disease as the best response were poor prognostic factors for PFS, while an ECOG PS of 2-3 and brain metastasis were associated with poor prognosis for OS. In addition, consolidative thoracic radiotherapy was found to be an independent favorable prognostic factor for OS (hazard ratio, 0.336; p=0.021). Grade ≥ 3 treatment-related adverse events were observed in 7% of patients, with treatment-related deaths occurring in 2% of patients.
Conclusion
We provided evidence of the favorable real-world effectiveness and safety of atezolizumab plus chemotherapy in ES-SCLC patients, including in the elderly and those with poor ECOG PS. Additional consolidative thoracic radiotherapy may also benefit ES-SCLC patients.

3,539 View
232 Download

Revolutionizing Non–Small Cell Lung Cancer Diagnosis: Ultra-High-Sensitive ctDNA Analysis for Detecting Hotspot Mutations with Long-term Stored Plasma: Ji-Young Lee, Seyeon Jeon, Ha Ra Jun, Chang Ohk Sung, Se Jin Jang, Chang-Min Choi, Sung-Min Chun; Cancer Res Treat. 2024;56(2):484-501. Published online October 23, 2023; DOI: https://doi.org/10.4143/crt.2023.712

Abstract PDF Supplementary Material PubReader ePub

Purpose
Circulating cell-free DNA (cfDNA) has great potential in clinical oncology. The prognostic and predictive values of cfDNA in non–small cell lung cancer (NSCLC) have been reported, with epidermal growth factor receptor (EGFR), KRAS, and BRAF mutations in tumor-derived cfDNAs acting as biomarkers during the early stages of tumor progression and recurrence. However, extremely low tumor-derived DNA rates hinder cfDNA application. We developed an ultra-high-sensitivity lung version 1 (ULV1) panel targeting BRAF, KRAS, and EGFR hotspot mutations using small amounts of cfDNA, allowing for semi-quantitative analysis with excellent limit-of-detection (0.05%).
Materials and Methods
Mutation analysis was performed on cfDNAs extracted from the plasma of 104 patients with NSCLC by using the ULV1 panel and targeted next-generation sequencing (CT-ULTRA), followed by comparison analysis of mutation patterns previously screened using matched tumor tissue DNA.
Results
The ULV1 panel demonstrated robust selective amplification of mutant alleles, enabling the detection of mutations with a high degree of analytical sensitivity (limit-of-detection, 0.025%-0.1%) and specificity (87.9%-100%). Applying ULV1 to NSCLC cfDNA revealed 51.1% (23/45) samples with EGFR mutations, increasing with tumor stage: 8.33% (stage I) to 78.26% (stage IV). Semi-quantitative analysis proved effective for low-mutation-fraction clinical samples. Comparative analysis with PANAMutyper EGFR exhibited substantial concordance (κ=0.84).
Conclusion
Good detection sensitivity (~80%) was observed despite the limited volume (1 mL) and long-term storage (12-50 months) of plasma used and is expected to increase with high cfDNA inputs. Thus, the ULV1 panel is a fast and cost-effective method for early diagnosis, treatment selection, and clinical follow-up of patients with NSCLC.

Citations

Citations to this article as recorded by

Longitudinal dynamics of circulating tumor DNA for treatment monitoring in patients with breast cancer recurrence
Tae-Kyung Robyn Yoo, Ji-Young Lee, Hwan Park, Whi-Kyung Cho, Seyeon Jeon, Ha Ra Jun, Sae Byul Lee, Il Yong Chung, Hee Jeong Kim, Beom Seok Ko, Jong Won Lee, Byung Ho Son, Sei-Hyun Ahn, Jae Ho Jeong, Jeong Eun Kim, Jin-Hee Ahn, Kyung Hae Jung, Sung-Bae Kim
Scientific Reports.2024;[Epub] CrossRef

3,077 View
136 Download
1 Web of Science
1 Crossref

Gastrointestinal cancer

Neoadjuvant Nivolumab Therapy for Esophageal Squamous Cell Carcinoma: A Single-Arm, Phase II Study: Sehhoon Park, Yurimi Lee, Jiyun Lee, Yang Won Min, Hong Kwan Kim, Joon Young Choi, Hyun Ae Jung, Yong Soo Choi, Yoon-La Choi, Young Mog Shim, Jong-Mu Sun; Cancer Res Treat. 2024;56(2):567-579. Published online October 16, 2023; DOI: https://doi.org/10.4143/crt.2023.897

Abstract PDF Supplementary Material PubReader ePub: Purpose
Programmed death-1/programmed death-ligand 1 (PD-L1) inhibitors have shown efficacy in metastatic esophageal squamous cell carcinoma (ESCC) therapy. However, data is still limited regarding neoadjuvant immunotherapy for operable ESCC.
Materials and Methods
Patients with clinical stage T2 or T3 and N0 ESCC received three cycles of nivolumab therapy every two weeks before surgical resection. The primary endpoint is major pathologic responses (MPR) rate (≤ 10% of residual viable tumor [RVT]).
Results
Total 20 patients completed the planned nivolumab therapy. Among them, 17 patients underwent surgery as protocol, showing MPR in two patients (MPR rate, 11.8%), including one pathologic complete response, on conventional pathologic response evaluation. Pathologic response was re-evaluated using the immune-related pathologic response criteria based on immune-related RVT (irRVT). Three patients were classified as immunologic major pathologic response (iMPR; ≤ 10% irRVT, iMPR rate: 17.6%), five as pathologic partial response (> 10% and < 90% irRVT), and nine as pathologic nonresponse (≥ 90% irRVT). The combined positive score (CPS) for PD-L1 in the baseline samples was predictable for iMPR, with the probability as 37.5% in CPS ≥ 10 (3/8) and 0% in CPS < 10 (0/9).
Conclusion
Although the efficacy of neoadjuvant nivolumab therapy was modest in unselected ESCC patients, further researches on neoadjuvant immunotherapy are necessary in patients with PD-L1 expressed ESCC.

3,389 View
162 Download

Genitourinary cancer

Clear Cell Adenocarcinoma of Urethra: Clinical and Pathologic Implications and Characterization of Molecular Aberrations: Boram Song, Seok Hyun Lee, Jeong Hwan Park, Kyung Chul Moon; Cancer Res Treat. 2024;56(1):280-293. Published online September 11, 2023; DOI: https://doi.org/10.4143/crt.2023.577

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to evaluate the molecular features of clear cell adenocarcinoma (CCA) of the urinary tract and investigate its pathogenic pathways and possible actionable targets.
Materials and Methods
We retrospectively collected the data of patients with CCA between January 1999 and December 2016; the data were independently reviewed by two pathologists. We selected five cases of urinary CCA, based on the clinicopathological features. We analyzed these five cases by whole exome sequencing (WES) and subsequent bioinformatics analyses to determine the mutational spectrum and possible pathogenic pathways.
Results
All patients were female with a median age of 62 years. All tumors were located in the urethra and showed aggressive behavior with disease progression. WES revealed several genetic alterations, including driver gene mutations (AMER1, ARID1A, CHD4, KMT2D, KRAS, PBRM1, and PIK3R1) and mutations in other important genes with tumor-suppressive and oncogenic roles (CSMD3, KEAP1, SMARCA4, and CACNA1D). We suggest putative pathogenic pathways (chromatin remodeling pathway, mitogen-activated protein kinase signaling pathway, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathway, and Wnt/β-catenin pathway) as candidates for targeted therapies.
Conclusion
Our findings shed light on the molecular background of this extremely rare tumor with poor prognosis and can help improve treatment options.

Citations

Citations to this article as recorded by

Urethral clear cell adenocarcinoma in an adult female: A rare case report
Yacob Sheiferawe Seman, Michael Teklehaimanot Abera, Fadil Nuredin Abrar, Tesfaye Kebede Legesse, Mesfin Asefa Tola, Tsiyon Nigusie Alemu
Urology Case Reports.2025; 58: 102882. CrossRef
Association between CACNA1D polymorphisms and hypospadias in a southern Chinese population
Ye He, Binyao Li, Xinying Zhao, Lingling Pan, Yanqing Liu, Chaoting Lan, Fuming Deng, Wen Fu, Yan Zhang, Xiaoyu Zuo
Journal of Pediatric Urology.2024; 20(3): 438.e1. CrossRef
The L‐type calcium channel CaV1.3: A potential target for cancer therapy
Xuerun Liu, Boqiang Shen, Jingyi Zhou, Juan Hao, Jianliu Wang
Journal of Cellular and Molecular Medicine.2024;[Epub] CrossRef

3,649 View
190 Download
3 Web of Science
3 Crossref

Lung and Thoracic cancer

Aggressive Local Ablative Radiotherapy Mitigates Progression Risk in Oligometastatic Lung Adenocarcinoma: Gowoon Yang, Kyung Hwan Kim, Chang Geol Lee, Min Hee Hong, Hye Ryun Kim, Yeona Cho, Hong In Yoon; Cancer Res Treat. 2024;56(1):115-124. Published online August 29, 2023; DOI: https://doi.org/10.4143/crt.2023.600

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study aimed to determine the role of local ablative radiotherapy (LART) in oligometastatic/oligoprogressive lung adenocarcinoma.
Materials and Methods
Patients (n=176) with oligometastatic lung adenocarcinoma treated with LART were identified, and those treated with LART at the initial diagnosis of synchronous oligometastatic disease (OMD group) or treated with LART when they presented with repeat oligoprogression (OPD group) were included.
Results
In the OMD group (n=54), the 1- and 3-year progression-free survival (PFS) were 50.9% and 22.5%, respectively, whereas the 1- and 3-year overall survival in the OPD group were 75.9% and 58.1%, respectively. Forty-one patients (75.9%) received LART at all gross disease sites. Tyrosine kinase inhibitor (TKI) use and all-metastatic site LART were significant predictors of higher PFS (p=0.018 and p=0.046, respectively). In patients treated with TKIs at the time of LART (n=23) and those treated with all-metastatic site LART, the 1-year PFS was 86.7%, while that of patients not treated with all-metastatic site LART was 37.5% (p=0.006). In the OPD group (n=122), 67.2% of the patients (n=82) maintained a systemic therapy regimen after LART. The cumulative incidence of changing systemic therapy was 39.6%, 62.9%, and 78.5% at 6 months, 1 year, and 2 years after LART, respectively.
Conclusion
Aggressive LART can be an option to improve survival in patients with oligometastatic disease. Patients with synchronous oligometastatic disease receiving TKI and all-metastatic site LART may have improved PFS. In patients with repeat oligoprogression, LART might potentially extend survival by delaying the need to change the systemic treatment regimen.

2,866 View
181 Download

Gastrointestinal cancer

Risk Stratification of Pancreatic Ductal Adenocarcinoma Patients Undergoing Curative-Intent Surgery after Neoadjuvant Therapy: Hyun Kyung Yang, Mi-Suk Park, Kyunghwa Han, Geonsik Eom, Yong Eun Chung, Jin-Young Choi, Seungmin Bang, Chang Moo Kang, Jinsil Seong, Myeong-Jin Kim; Cancer Res Treat. 2024;56(1):247-258. Published online August 22, 2023; DOI: https://doi.org/10.4143/crt.2023.586

Abstract PDF Supplementary Material PubReader ePub: Purpose
Clinical prognostic criteria using preoperative factors were not developed for post–neoadjuvant therapy (NAT) surgery of pancreatic ductal adenocarcinoma (PDAC). We aimed to identify preoperative factors associated with overall survival (OS) in PDAC patients who underwent post-NAT curative-intent surgery and develop risk stratification criteria.
Materials and Methods
Consecutive PDAC patients who underwent post-NAT curative-intent surgeries between 2007 and 2020 were retrospectively analyzed. Demographic, laboratory, surgical, and histopathologic variables were collected. Baseline, preoperative, and interval changes of computed tomography (CT) findings proposed by the Society of Abdominal Radiology and the American Pancreatic Association were analyzed. Cox proportional hazard analysis was used to select preoperative variables associated with OS. We developed risk stratification criteria composed of the significant preoperative variables, i.e., post-NAT response criteria. We compared the discrimination performance of post-NAT response criteria with that of post-NAT pathological (yp) American Joint Cancer Committee TNM staging system.
Results
One hundred forty-five PDAC patients were included. Stable or increased tumor size on CT (hazard ratio [HR], 2.58; 95% confidence interval [CI], 1.58 to 4.21; p < 0.001) and elevated preoperative carbohydrate antigen 19-9 (CA19-9) level (HR, 1.98; 95% CI, 1.11 to 3.55; p=0.021) were independent factors of OS. The OS of the patient groups stratified by post-NAT response criteria which combined changes in tumor size and CA19-9 showed significant difference (p < 0.001). Such stratification was comparable to ypTNM staging in discrimination performance (difference of C-index, 0.068; 95% CI, –0.012 to 0.142).
Conclusion
“Any degree of decrease in tumor size on CT” and CA19-9 normalization or staying normal were independent favorable factors of OS. The combination of the two factors discriminated OS comparably to ypTNM staging.

2,678 View
164 Download

Search