Miso Kim, Hyo Sup Shim, Sheehyun Kim, In Hee Lee, Jihun Kim, Shinkyo Yoon, Hyung-Don Kim, Inkeun Park, Jae Ho Jeong, Changhoon Yoo, Jaekyung Cheon, In-Ho Kim, Jieun Lee, Sook Hee Hong, Sehhoon Park, Hyun Ae Jung, Jin Won Kim, Han Jo Kim, Yongjun Cha, Sun Min Lim, Han Sang Kim, Choong-kun Lee, Jee Hung Kim, Sang Hoon Chun, Jina Yun, So Yeon Park, Hye Seung Lee, Yong Mee Cho, Soo Jeong Nam, Kiyong Na, Sun Och Yoon, Ahwon Lee, Kee-Taek Jang, Hongseok Yun, Sungyoung Lee, Jee Hyun Kim, Wan-Seop Kim
Cancer Res Treat. 2024;56(3):721-742. Published online November 29, 2023
In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.
Ki Hyeong Lee, Byoung Chul Cho, Myung-Ju Ahn, Yun-Gyoo Lee, Youngjoo Lee, Jong-Seok Lee, Joo-Hang Kim, Young Joo Min, Gyeong-Won Lee, Sung Sook Lee, Kyung-Hee Lee, Yoon Ho Ko, Byoung Yong Shim, Sang-We Kim, Sang Won Shin, Jin-Hyuk Choi, Dong-Wan Kim, Eun Kyung Cho, Keon Uk Park, Jin-Soo Kim, Sang Hoon Chun, Jangyoung Wang, SeokYoung Choi, Jin Hyoung Kang
Cancer Res Treat. 2024;56(1):48-60. Published online June 27, 2023
Purpose This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non–small cell lung cancer (NSCLC).
Materials and Methods Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS).
Results In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment–related AEs occurred with lazertinib than gefitinib.
Conclusion Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.
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Kyu Hye Choi, Jin Ho Song, Yeon-Sil Kim, Ji-hoon Kim, Woo-Jin Jeong, Inn-Chul Nam, Jin Ho Kim, Hee Kyung Ahn, Sang Hoon Chun, Hyun Jun Hong, Young-Hoon Joo, Young-Gyu Eun, Sung Ho Moon, Jeongshim Lee
Cancer Res Treat. 2021;53(4):1004-1014. Published online January 29, 2021
Purpose The incidence of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) has increased, and staging and optimal therapeutic approaches are challenging. A questionnaire survey was conducted to investigate the controversial treatment policy of stage T2 OPC according to the N category and determine the opinions of multidisciplinary experts in Korea.
Materials and Methods Five OPC scenarios were developed by the Subcommittee on Oropharyngeal Treatment Guidelines of the Korean Society for Head and Neck Oncology and distributed to experts of multidisciplinary treatment hospitals.
Results Sixty-five experts from 45 institutions responded. For the HPV-positive T2N0M0 scenario, 67.7% of respondents selected surgery followed by definitive concurrent chemoradiotherapy (CCRT) or radiotherapy alone. For the T2N1M0 HPV-positive scenario, there was a notable difference in the selection of primary treatment by expert specialty; 53.9% of respondents selected surgery and 39.8% selected definitive CCRT as the primary treatment. For the T2N3M0 advanced HPV-positive scenario, 50.0% of respondents selected CCRT and 33.3% considered induction chemotherapy (IC) as the primary treatment. CCRT and IC were significantly more frequently selected for the HPV-related OPC cases (p=0.010). The interdepartmental variability showed that the head and neck surgeons and medical oncologists favored surgery, whereas the radiation oncologists preferably selected definitive CCRT (p < 0.001).
Conclusion In this study, surgery was preferred for lymph node-negative OPC, and as lymph node metastasis progressed, CCRT tended to be preferred, and IC was administered. Clinical practice patterns by stage and HPV status showed differences according to expert specialty. Multidisciplinary consensus guidelines will be essential in the future.
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Controversies in Lung Cancer: Heterogeneity in Treatment Recommendations for Stage III NSCLC According to Disease Burden and Oncogenic Driver Alterations Jeremy P Harris, Dylann K Fujimoto, Misako Nagasaka, Eric Ku, Garrett Harada, Hari Keshava, Ali Mahtabifard, Javier Longoria, Niral Patel, Steven Seyedin, Aaron Simon, Allen Chen Clinical Lung Cancer.2022; 23(4): 333. CrossRef
Survey of radiation field and dose in human papillomavirus-positive oropharyngeal cancer: is de-escalation actually applied in clinical practice? Kyu Hye Choi, Jin Ho Song, Yeon-Sil Kim, Sung Ho Moon, Jeongshim Lee, Young-Taek Oh, Dongryul Oh, Jin Ho Kim, Jun Won Kim Radiation Oncology Journal.2021; 39(3): 174. CrossRef
Yun-Gyoo Lee, Hyun Chang, Bhumsuk Keam, Sang Hoon Chun, Jihyun Park, Keon Uk Park, Seong Hoon Shin, Ho Jung An, Kyoung Eun Lee, Keun-Wook Lee, Hye Ryun Kim, Sung-Bae Kim, Myung-Ju Ahn, In Gyu Hwang
Cancer Res Treat. 2021;53(3):671-677. Published online December 7, 2020
Purpose This study was conducted to determine the effectiveness of immune checkpoint inhibitors (ICIs) in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) after platinum-containing chemotherapy. We also identified clinical biomarkers which may be predictive of patient prognosis.
Materials and Methods We analyzed 125 patients with R/M HNSCC who received ICIs, retrospectively. Overall response rate (ORR) was the primary study outcome. Overall survival (OS) and progression-free survival (PFS) were the secondary study outcomes.
Results The patients received anti–programmed cell death protein-1 (PD-1) (n=73, 58%), anti–programmed death-ligand 1 (PD-L1) (n=24, 19%), or a combination of anti–PD-1/PD-L1 and anti–cytotoxic T-lymphocyte antigen 4 (n=28, 22%). The median age was 57 years (range, 37 to 87). The location of the primary tumor was in the oral cavity in 28% of the cases, followed by oropharynx (27%), hypopharynx (20%), and larynx (12%). The ORR was 15% (19/125). With 12.3 months of median follow-up, median PFS was 2.7 months. Median OS was 10.8 months. A neutrophil-to-lymphocyte ratio (NLR) > 4 was significantly associated with poor response to ICIs (odds ratio, 0.30; p=0.022). A sum of the target lesions > 40 mm (hazard ratio [HR], 1.53; p=0.046] and a NLR > 4 (HR, 1.75; p=0.009) were considered to be predictive markers of short PFS. A poor performance status (HR, 4.79; p < 0.001), a sum of target lesions > 40 mm (HR, 1.93; p=0.025), and an NLR > 4 (HR, 3.36; p < 0.001) were the significant predictors for poor survival.
Conclusion ICIs exhibited favorable antitumor activity in R/M HNSCC. Clinically, our findings can be used to recognize patients benefit from receiving ICI.
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Cancer Res Treat. 2021;53(2):409-423. Published online October 28, 2020
Purpose
Use of cyclin-dependent kinase 4/6 inhibitors improved survival outcome of hormone receptor (HR) positive metastatic breast cancer (MBC) patients, including Asian population. However, Asian real-world data of palbociclib is limited. We analyzed the real-world clinical practice patterns and outcome in HR-positive, MBC Asian patients treated with palbociclib.
Materials and Methods
Between April 2017 to November 2019, 169 HR-positive, human epidermal growth factor-2–negative MBC patients treated with letrozole or fulvestrant plus palbocilib were enrolled from eight institutions. Survival outcome (progression-free survival [PFS]), treatment response and toxicity profiles were analyzed.
Results
Median age of letrozole plus palbociclib (145 patients, 85.8%) and fulvestrant plus palbociclib (24 patients, 14.2%) was 58 and 53.5 years, with median follow-up duration of 14.63 months (range 0.2 to 33.9 months). Median PFS (mPFS) of letrozole plus palbociclib and fulvestrant plus palbociclib was 25.6 (95% confidence interval [CI], 19.1 to not reached) and 6.37 months (95% CI, 5.33 to not reached), comparable to previous phase 3 trials. In letrozole plus palbociclib arm, luminal A (hazard ratio, 2.86; 95% CI, 1.20 to 6.80; p=0.017) and patients with good performance (Eastern Cooperative Oncology Group 0-1 [hazard ratio, 3.68; 95% CI, 1.70 to 7.96]) showed better mPFS. In fulvestrant plus palbociclib group, chemotherapy naïve patients showed better mPFS (hazard ratio, 12.51, 95% CI, 1.59 to 99.17; p=0.017). The most common grade 3 or 4 adverse event was neutropenia (letrozole 86.3%, fulvestrant 88.3%).
Conclusion
To our knowledge, this is the first real-world data of palbociclib reported in Asia. Palbociclib showed comparable benefit to previous phase 3 trials in Asian patients during daily clinical practice.
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Cancer Res Treat. 2019;51(4):1632-1638. Published online April 18, 2019
Purpose
Physician Orders for Life-Sustaining Treatment (POLST) form is a legal document for terminally ill patients to make medical decisions with physicians near the end-of-life. A multicenter prospective study was conducted to evaluate the feasibility of POLST administration in actual oncological practice.
Materials and Methods
Patients with terminal cancer, age ≥ 20 years, and capable of communicating were eligible. The primary endpoint was the completion rate of POLST. Data about physicians’ or patients’ barriers were also collected.
Results
From June to December 2017, 336 patients from seven hospitals were eligible. Median patient age was 66 years (range, 20 to 94 years); 52.7% were male; and 60.4% had poor performance status. Primary cancer sites were hepato-pancreato-biliary (26.2%), lung (23.2%), and gastrointestinal (19.9%). Expected survival duration was 10.6±7.3 weeks, with 41.2% receiving hospice care, 37.9% showing progression after cancer treatment, and the remaining patients were under active treatment (15.8%) or initially diagnosed with terminal cancer (5.1%). POLST forms were introduced to 60.1% of patients, and 31.3% signed the form. Physicians’ barriers were reluctance of family (49.7%), lack of rapport (44.8%), patients’ denial of prognosis (34.3%), lack of time (22.7%), guilty feelings (21.5%), and uncertainty about either prognosis (21.0%) or the right time to discuss POLST (16.6%). The patients’ barriers were the lack of knowledge/understanding of POLST (65.1%), emotional discomfort (63.5%), difficulty in decision-making (66.7%), or denial of prognosis (14.3%).
Conclusion
One-third of patients completed POLST forms, and various barriers were identified. To overcome such barriers, social engagement, education, and systematic support might be necessary.
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Sun Min Lim, Sang Hee Cho, In Gyu Hwang, Jae Woo Choi, Hyun Chang, Myung-Ju Ahn, Keon Uk Park, Ji-Won Kim, Yoon Ho Ko, Hee Kyung Ahn, Byoung Chul Cho, Byung-Ho Nam, Sang Hoon Chun, Ji Hyung Hong, Jung Hye Kwon, Jong Gwon Choi, Eun Joo Kang, Tak Yun, Keun-Wook Lee, Joo-Hang Kim, Jin Soo Kim, Hyun Woo Lee, Min Kyoung Kim, Dongmin Jung, Ji Eun Kim, Bhumsuk Keam, Hwan Jung Yun, Sangwoo Kim, Hye Ryun Kim
Cancer Res Treat. 2019;51(1):300-312. Published online May 9, 2018
Purpose
Head and neck squamous cell carcinoma (HNSCC) is a deadly disease in which precision medicine needs to be incorporated. We aimed to implement next-generation sequencing (NGS) in determining actionable targets to guide appropriate molecular targeted therapy in HNSCC patients.
Materials and Methods
Ninety-three tumors and matched blood samples underwent targeted sequencing of 244 genes using the Illumina HiSeq 2500 platform with an average depth of coverage of greater than 1,000×. Clinicopathological data from patients were obtained from 17 centers in Korea, and were analyzed in correlation with NGS data.
Results
Ninety-two of the 93 tumors were amenable to data analysis. TP53 was the most common mutation, occurring in 47 (51%) patients, followed by CDKN2A (n=23, 25%), CCND1 (n=22, 24%), and PIK3CA (n=19, 21%). The total mutational burden was similar between human papillomavirus (HPV)–negative vs. positive tumors, although TP53, CDKN2A and CCND1 gene alterations occurred more frequently in HPV-negative tumors. HPV-positive tumors were significantly associated with immune signature-related genes compared to HPV-negative tumors. Mutations of NOTCH1 (p=0.027), CDKN2A (p < 0.001), and TP53 (p=0.038) were significantly associated with poorer overall survival. FAT1 mutations were highly enriched in cisplatin responders, and potentially targetable alterations such as PIK3CA E545K and CDKN2A R58X were noted in 14 patients (15%).
Conclusion
We found several targetable genetic alterations, and our findings suggest that implementation of precision medicine in HNSCC is feasible. The predictive value of each targetable alteration should be assessed in a future umbrella trial using matched molecular targeted agents.
Citations
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A 56-year-old female was referred to our hospital due to a mass measuring 5 cm in size in the left pelvic cavity, which was found incidentally during a health examination by ultrasonography. Exploratory laparotomy was performed and the mass was located at the left retroperitoneal parametrium without invasion of the uterus and ovary. The pathology report confirmed squamous cell carcinoma. Even after further studies, we did not find any other primary lesion. Human papillomavirus (HPV) DNA chip test (HPV 9G DNA Membrane Kit, Biometrixtechnology Inc.) showed that the surgical specimen was positive for HPV 18. She received adjuvant chemotherapy and would receive radiation therapy for the possibility of occult gynecologic cancer. Retroperitoneal squamous cell carcinoma of unknown primary is extremely rare and little is known about it. It is reported that HPV may be associated with the disease. Hence, the result of HPV test could have an impact on finding a suspicious primary lesion and treatment modality in this case.
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Purpose
In order to provide effective hospice care, adequate length of survival (LOS) in hospice is necessary. However the reported average LOS is much shorter. Analysis of LOS in hospice has not been reported from Korea. We evaluated the duration of LOS and the factors associated with LOS at our hospice center.
Materials and Methods
We retrospectively examined 446 patients who were admitted to our hospice unit between January 2010 and December 2012. We performed univariate and multivariate analysis for analysis of factors associated with LOS.
Results
The median LOS was 9.5 days (range, 1 to 186 days). The LOS of 389 patients (86.8%) was< 1 month. At the time of admission to hospice, 112 patients (25.2%) were completely bedridden, 110 patients (24.8%) had mouth care only without intake, and 134 patients (30.1%) had decreased consciousness, from confusion to coma. The median time interval between the day of the last anticancer treatment and the day of hospice admission was 75 days. By analysis of the results of multivariate analysis, decreased intake and laboratory results showing increased total white blood cell (WBC), decreased platelet count, increased serum creatinine, increased aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) level were poor prognostic factors for survival in hospice.
Conclusion
Before hospice admission, careful evaluation of the patient’s performance, particularly the oral intake, and total WBC, platelet, creatinine, AST, ALT, and LDH level is essential, because these were strong predictors of shorter LOS. In the future, conduct of prospective controlled studies is warranted in order to confirm the relationship between potential prognostic factors and LOS in hospice.
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PURPOSE This study aimed to analyze the efficacy and toxicity of gemcitabine plus platinum chemotherapy for patients aged 70 years or older with advanced non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS We reviewed the records of stage IIIB, IV NSCLC patients or surgically inoperable stage II, IIIA NSCLC patients who were aged 70 years or older when treated with gemcitabine (1,250 mg/m2) plus cisplatin (75 mg/m2) or carboplatin (AUC5) chemotherapy from 2001 to 2010 at Seoul St. Mary's Hospital, Uijeongbu St. Mary's Hospital and St. Vincent's Hospital. Gemcitabine was administered on days 1 and 8, and cisplatin or carboplatin was administered on day 1. Treatments were repeated every 3 weeks for a maximum of 4 cycles. RESULTS The median age of the 62 patients was 73.5 years (range, 70 to 84 years). Forty-one (66%) patients exhibited comorbidity. The mean number of treatment cycles was 3.9.
The compared average relative dose intensity of gemcitabine plus platinum chemotherapy was 84.8%. The median progression-free survival and overall survival (OS) were 5.0 months and 9.4 months, respectively. Reduced Eastern Cooperative Oncology Group (ECOG) performance status (none vs. > or =1) and weight loss (<5% vs. > or =5%) after treatment were found to have a significant effect on OS (p=0.01). CONCLUSION Gemcitabine plus platinum chemotherapy is an effective treatment option with an acceptable level of toxicity in patients aged 70 years or older with good performance status in advanced NSCLC.
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