Cancer Research and Treatment

Original Articles

Validating the Korean Geriatric Assessment Tool in Elderly Multiple Myeloma Patients: A Multicenter Study: Ji Yun Lee, Sang-A Kim, Youngil Koh, Ho-Young Yhim, Gyeong-Won Lee, Chang-Ki Min, Young Rok Do, Hyo Jung Kim, Sung Hwa Bae, Hyeon-Seok Eom, Sung-Hoon Jung, Hyunkyung Park, Seung-Hyun Nam, Ji Hyun Lee, Sung-Hyun Kim, Hyun Jung Lee, Young Seob Park, Soo-Mee Bang; Received January 15, 2025 Accepted February 20, 2025 Published online February 21, 2025; DOI: https://doi.org/10.4143/crt.2025.066 [Accepted]

Abstract PDF: Purpose
This study evaluates the Korean Cancer Study Group Geriatric Score-7 (KG-7) frailty screening tool's effectiveness in elderly multiple myeloma (MM) patients to prevent under and over-treatment.
Materials and Methods
This prospective pilot cohort study included 100 elderly patients aged 70 and older with newly diagnosed MM who had not undergone transplantation from August 2020 to January 2022.
Results
The median age was 77 years, and 73% of patients were classified at International Staging System (ISS) stages 2 or 3. Using a 5-point cutoff on the KG-7 index (non-frail, score ≥ 5; frail, score < 5), 31% were categorized as frail. After a median follow-up of 26.8 months, the 3-year overall survival rate was 73.0%. There was no statistically significant association between any frailty index and the risk of death. However, frail patients defined by the simplified frailty index (HR, 2.49; 95% CI, 1.09–5.95; p=0.030) and by KG-7 (HR, 2.43; 95% CI, 1.03–5.86; p=0.043) had a significantly higher risk of grade 3–4 non-hematologic toxicity, whereas the IMWG definition did not. Over a 24-month tracking period, vulnerability as measured by KG-7 either improved or deteriorated.
Conclusion
The pilot study, which had a limited number of participants, did not demonstrate KG-7’s effectiveness in predicting survival; however, it successfully predicted severe non-hematologic toxicities. We plan to conduct larger studies in elderly MM patients to determine whether KG-7 can help tailor their treatment regimens.

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ALYREF-Mediated Regulation of TBL1XR1 and KMT2E Synergistically Upregulates APOC1, Contributing to Oxaliplatin Resistance in Esophageal Cancer: Jie Hu, Qilong Liu, Bi Feng, Yanling Lu, Kai Chen; Received November 15, 2024 Accepted February 3, 2025 Published online February 4, 2025; DOI: https://doi.org/10.4143/crt.2024.1091 [Accepted]

Abstract PDF: Purpose
Esophageal cancer (EC) is a rapidly progressing malignancy characterized by a low survival rate and limited treatment success, largely due to late-stage detection, frequent recurrence, and a high propensity for metastasis, despite ongoing advances in therapeutic strategies. While oxaliplatin (L-OHP) is a potent chemotherapeutic agent that induces apoptosis in EC cells, its effectiveness is significantly hindered by the development of resistance.
Materials and Methods
The assessment of gene and protein expression was conducted through a combination of RT-qPCR, Western blot, and IHC staining. Cell viability was assessed using the CCK-8 assay. The interactions among ALYREF, TBL1XR1, KMT2E, and APOC1 were investigated through RIP, ChIP, ChIP-reChIP, RNA pulldown, and dual-luciferase assays. An in vivo mouse model of EC was established.
Results
Expression levels of both APOC1 and ALYREF were elevated in L-OHP-resistant EC tissues and cell lines, and their silencing enhanced sensitivity to L-OHP. TBL1XR1 and KMT2E synergistically upregulated APOC1 expression. Moreover, ALYREF recognized the m5C sites on TBL1XR1 and KMT2E mRNAs, stabilizing these transcripts and promoting APOC1 expression. The regulatory role of these interactions was further validated in vivo.
Conclusion
This study demonstrated that ALYREF interacted with the m5C sites on TBL1XR1 and KMT2E mRNAs, enhancing their stability and leading to increased transcription of APOC1, which in turn contributed to L-OHP resistance in EC. These findings suggest that targeting APOC1 could be a promising strategy for overcoming L-OHP resistance in EC.

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To Use or Not to Use: Temozolomide in Elderly Patients with IDH Wild-Type MGMT Promoter Unmethylated Glioblastoma Treated with Radiotherapy: Chan Woo Wee, Joo Ho Lee, Hye In Lee, Jina Kim, Jong Hee Chang, Seok-Gu Kang, Eui Hyun Kim, Ju Hyung Moon, Jaeho Cho, Chul-Kee Park, Chae-Yong Kim, Kihwan Hwang, Hong In Yoon, In Ah Kim; Received September 27, 2024 Accepted November 8, 2024 Published online November 11, 2024; DOI: https://doi.org/10.4143/crt.2024.945 [Epub ahead of print]

Abstract PDF PubReader ePub: Purpose
This study aimed to identify a specific subgroup of patients among elderly glioblastoma patients aged 70 years or older with unmethylated O6-methylguanine-DNA methyltransferase promoters (eGBM-unmethylated) who would significantly benefit from the addition of temozolomide (TMZ) to radiotherapy (RT).
Materials and Methods
Newly diagnosed patients with Isocitrate dehydrogenase wild-type eGBM-unmethylated treated with RT were included in this multicenter analysis (n=182). RT dose was 45 Gy in 15 fractions (62.3%), 60 Gy in 30 fractions, or 61.2 Gy in 34 fractions. For patients treated with RT plus TMZ (60.4%), TMZ was administered concurrently with RT, followed by six adjuvant cycles. The primary endpoint was overall survival.
Results
During a median follow-up of 11.3 months for survivors, the median survival was 12.2 months. The median survival duration significantly improved with the addition of TMZ to RT compared with that with RT alone (13.6 months vs. 10.5 months, p=0.028). In the multivariable analysis adjusted for clinical, radiological, and genetic biomarkers, the addition of TMZ significantly improved overall survival (hazard ratio, 0.459; p=0.006). In subgroup analysis, median survival was especially improved by 4-5 months in patients with residual disease (p < 0.001), Karnofsky performance status ≥ 60 (p=0.033), and age ≤ 75 years (p=0.090). A significant benefit of TMZ was noted only in patients with two or three of the above factors (median survival, 14.1 months vs. 10.5 months; p=0.014).
Conclusion
The addition of TMZ significantly improved the survival of patients with eGBM-unmethylated treated with RT. The suggested criteria for the specific subgroup in these patients warrant external validation for clinical application.

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Is Colonoscopy Alone Adequate for Surveillance in Stage I Colorectal Cancer?: Seijong Kim, Jung Kyong Shin, Yoonah Park, Jung Wook Huh, Hee Cheol Kim, Seong Hyeon Yun, Woo Yong Lee, Yong Beom Cho; Received June 4, 2024 Accepted October 2, 2024 Published online October 4, 2024; DOI: https://doi.org/10.4143/crt.2024.526 [Epub ahead of print]

Abstract PDF PubReader ePub: Purpose
While colonoscopy is the standard surveillance tool for stage I colorectal cancer according to National Comprehensive Cancer Network guidelines, its effectiveness in detecting recurrence is debated. This study evaluates recurrence risk factors and patterns in stage I colorectal cancer to inform comprehensive surveillance strategies.
Materials and Methods
A retrospective analysis of 2,248 stage I colorectal cancer patients who underwent radical surgery at Samsung Medical Center (2007-2018) was conducted. Exclusions were based on familial history, prior recurrences, preoperative treatments, and inadequate data. Surveillance included colonoscopy, laboratory tests, and computed tomography (CT) scans.
Results
Stage I colorectal cancer patients showed favorable 5-year disease-free survival (98.3% colon, 94.6% rectum). Among a total of 1,467 colon cancer patients, 26 (1.76%) experienced recurrence. Of the 781 rectal cancer patients, 47 (6.02%) experienced recurrence. Elevated preoperative carcinoembryonic antigen levels and perineural invasion were significant recurrence risk factors in colon cancer, while tumor budding was significant in rectal cancer. Distant metastasis was the main recurrence pattern in colon cancer (92.3%), while rectal cancer showed predominantly local recurrence (50%). Colonoscopy alone detected recurrences in a small fraction of cases (3.7% in colon, 14.9% in rectum).
Conclusion
Although recurrence in stage I colorectal cancer is rare, relying solely on colonoscopy for surveillance may miss distant metastases or locoregional recurrence outside the colorectum. For high-risk patients, we recommend considering regular CT scans alongside colonoscopy. This targeted approach may enable earlier recurrence detection and improve outcomes in this subset while avoiding unnecessary scans for the low-risk majority.

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The Role of Direct Oral Anticoagulants in Managing Myeloproliferative Neoplasms Patients: Ji Yun Lee, Ju-Hyun Lee, Woochan Park, Jeongmin Seo, Minsu Kang, Eun Hee Jung, Sang-A Kim, Koung Jin Suh, Ji-Won Kim, Se Hyun Kim, Jeong-Ok Lee, Jin Won Kim, Yu Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Soo-Mee Bang; Received August 5, 2024 Accepted September 19, 2024 Published online September 20, 2024; DOI: https://doi.org/10.4143/crt.2024.738 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub

Purpose
Thrombosis and bleeding significantly affect morbidity and mortality in myeloproliferative neoplasms (MPNs). The efficacy and safety of direct oral anticoagulants (DOACs) in MPN patients remain uncertain.
Materials and Methods
We conducted a large, retrospective, nationwide cohort study using the Korean Health Insurance Review and Assessment Service database from 2010 to 2021.
Results
Out of the 368 MPN patients included in the final analysis, 62.8% were treated with DOACs for atrial fibrillation (AF), and 37.2% for venous thromboembolism (VTE). The AF group was statistically older with higher CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke, transient ischemic attack, or thromboembolism, vascular disease, age 65-74 years, sex category [female]) scores compared to the VTE group. Antiplatelet agents were used in 51.1% of cases, and cytoreductive drugs in 79.3%, with hydroxyurea being the most common (64.9%). The median follow-up was 22.3 months, with 1-year cumulative incidence rates of thrombosis and bleeding at 11.1% and 3.7%, respectively. Multivariate analysis identified CHA2DS2-VASc scores ≥ 3 (hazard ratio [HR], 3.48), concomitant antiplatelet use (HR, 2.57), and cytoreduction (HR, 2.20) as significant thrombosis risk factors but found no significant predictors for major bleeding.
Conclusion
Despite the limitations of retrospective data, DOAC treatment in MPN patients seems effective and has an acceptable bleeding risk.

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Survey of Clinical Practice in Chronic Myeloproliferative Neoplasms in Croatia: A Study by the MPN Working Group Party of the Croatian Cooperative Group for Hematologic Diseases (KROHEM)
Ivan Krecak, Marko Lucijanic, Rajko Kusec
Journal of Clinical Medicine.2025; 14(5): 1524. CrossRef

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Choosing Wisely between Radiotherapy Dose-Fractionation Schedules: The Molecular Graded Prognostic Assessment for Elderly Glioblastoma Patients: Hye In Lee, Jina Kim, In Ah Kim, Joo Ho Lee, Jaeho Cho, Rifaquat Rahman, Geoffrey Fell, Chan Woo Wee, Hong In Yoon; Received July 22, 2024 Accepted September 10, 2024 Published online September 11, 2024; DOI: https://doi.org/10.4143/crt.2024.680 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study aimed to develop a graded prognostic assessment (GPA) model integrating genomic characteristics for elderly patients with glioblastoma (eGBM), and to compare the efficacy of different radiotherapy schedules.
Materials and Methods
This multi-institutional retrospective study included patients aged ≥ 65 years who underwent surgical resection followed by radiotherapy with or without temozolomide (TMZ) for newly diagnosed eGBM. Based on the significant factors identified in the multivariate analysis for overall survival (OS), the molecular GPA for eGBM (eGBM-molGPA) was established.
Results
A total of 334 and 239 patients who underwent conventionally fractionated radiotherapy (CFRT) and hypofractionated radiotherapy (HFRT) were included, respectively, with 86% of patients receiving TMZ-based chemoradiation. With a median follow-up of 17.4 months (range, 3.3 to 149.9 months), the median OS was 18.7 months for CFRT+TMZ group, 15.1 months for HFRT+TMZ group, and 10.4 months for radiotherapy alone group (CFRT+TMZ vs. HFRT+TMZ: hazard ratio [HR], 1.52; p < 0.001 and CFRT+TMZ vs. radiotherapy alone: HR, 2.52; p < 0.001). In a combined analysis with the NOA-08 and Nordic trials, CFRT+TMZ group exhibited the highest survival rates among all treatment groups. The eGBM-molGPA, which integrated four clinical and three molecular parameters, stratified patients into low-, intermediate-, and high-risk groups. CFRT+TMZ significantly improved OS compared to HFRT+TMZ or radiotherapy alone in the low-risk (p=0.023) and intermediate-risk groups (p < 0.001). However, in the high-risk group, there was no significant difference in OS between treatment options (p=0.770).
Conclusion
CFRT+TMZ may be more effective than HFRT+TMZ or radiotherapy alone for selected eGBM patients. The novel eGBM-molGPA model can guide treatment selection for this patient population.

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Gastrointestinal cancer

Salvage Radiotherapy for Loco-regional Recurrence of Esophageal Cancer Following Surgery: Won Kyung Cho, Jae Myoung Noh, Dongryul Oh, Yong Chan Ahn, Jong-Mu Sun, Hong Kwan Kim, Young Mog Shim; Cancer Res Treat. 2025;57(1):165-173. Published online July 26, 2024; DOI: https://doi.org/10.4143/crt.2024.191

Abstract PDF Supplementary Material PubReader ePub

Purpose
There is few evidence regarding the optimal salvage treatment options for loco-reginal recurrence of esophageal cancer. This study aimed to evaluate the clinical outcomes of salvage radiotherapy (RT) in patients with loco-regional recurrence (LRR) after surgery for esophageal cancer.
Materials and Methods
We retrospectively reviewed 147 esophageal cancer patients who received salvage RT for loco-regional recurrence between 1996 and December 2019. A total dose of 60 Gy in 20 fractions was used for RT alone and 60-70 Gy in 30-35 fractions for concurrent chemoradiotherapy (CCRT).
Results
The patients’ median age was 65 years (range, 41 to 86 years). The median disease-free interval was 13.5 months (1.0 to 97.4 months). After a median 18.8 months follow-up, the 2-year overall survival (OS) and progression-free survival (PFS) rates were 38.1% and 25.9%, respectively. The median OS and PFS were 18.8 and 8.4 months, respectively. The CCRT could not improve OS compared to RT (p=0.336), but there was a trend of better PFS in the CCRT group. Regarding toxicities, the rate of grade 3 or higher toxicity was 10.9% occurring in 16 patients, and it was higher in patients who received CCRT than in the RT alone group (19.6% vs. 6.3%, p=0.023).
Conclusion
Salvage RT alone as well as CCRT could be effective in patients with locoregionally recurrent esophageal cancer.

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Salvage Chemoradiotherapy for Loco-Regional Recurrence of Esophageal Squamous Cell Carcinoma After Esophagectomy
Atsuto Katano, Tomoki Kiritoshi, Subaru Sawayanagi, Hideomi Yamashita
Journal of Clinical Medicine.2025; 14(5): 1540. CrossRef

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Pediatric cancer

Stratified Treatment in Pediatric Anaplastic Large Cell Lymphoma: Result of a Prospective Open-Label Multiple-Institution Study: Tingting Chen, Chenggong Zeng, Juan Wang, Feifei Sun, Junting Huang, Jia Zhu, Suying Lu, Ning Liao, Xiaohong Zhang, Zaisheng Chen, Xiuli Yuan, Zhen Yang, Haixia Guo, Liangchun Yang, Chuan Wen, Wenlin Zhang, Yang Li, Xuequn Luo, Zelin Wu, Lihua Yang, Riyang Liu, Mincui Zheng, Xiangling He, Xiaofei Sun, Zijun Zhen; Cancer Res Treat. 2024;56(4):1252-1261. Published online May 28, 2024; DOI: https://doi.org/10.4143/crt.2024.104

Abstract PDF Supplementary Material PubReader ePub: Purpose
The risk stratification of pediatric anaplastic large cell lymphoma (ALCL) has not been standardized. In this study, new risk factors were included to establish a new risk stratification system for ALCL, and its feasibility in clinical practice was explored.
Materials and Methods
On the basis of the non-Hodgkin’s lymphoma Berlin–Frankfurt–Munster 95 (NHL-BFM-95) protocol, patients with minimal disseminated disease (MDD), high-risk tumor site (multiple bone, skin, liver, and lung involvement), and small cell/lymphohistiocytic (SC/LH) pathological subtype were enrolled in risk stratification. Patients were treated with a modified NHL-BFM-95 protocol combined with an anaplastic lymphoma kinase inhibitor or vinblastine (VBL).
Results
A total of 136 patients were enrolled in this study. The median age was 8.8 years. The 3-year event-free survival (EFS) and overall survival of the entire cohort were 77.7% (95% confidence interval [CI], 69.0% to 83.9%) and 92.3% (95% CI, 86.1% to 95.8%), respectively. The 3-year EFS rates of low-risk group (R1), intermediate-risk group (R2), and high-risk group (R3) patients were 100%, 89.5% (95% CI, 76.5% to 95.5%), and 67.9% (95% CI, 55.4% to 77.6%), respectively. The prognosis of patients with MDD (+), stage IV cancer, SC/LH lymphoma, and high-risk sites was poor, and the 3-year EFS rates were 45.3% (95% CI, 68.6% to 19.0%), 65.7% (95% CI, 47.6% to 78.9%), 55.7% (95% CI, 26.2% to 77.5%), and 70.7% (95% CI, 48.6% to 84.6%), respectively. At the end of follow-up, one of the five patients who received maintenance therapy with VBL relapsed, and seven patients receiving anaplastic lymphoma kinase inhibitor maintenance therapy did not experience relapse.
Conclusion
This study has confirmed the poor prognostic of MDD (+), high-risk site and SC/LH, but patients with SC/LH lymphoma and MDD (+) at diagnosis still need to receive better treatment (ClinicalTrials.gov number, NCT03971305).

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Gastrointestinal cancer

Association between Endoscopist Volume and Interval Cancers after Colonoscopy: Results from the National Colorectal Cancer Screening Program in Korea: Dong Jun Kim, Nan-He Yoon, Jae Kwan Jun, Mina Suh, Sunhwa Lee, Seongju Kim, Ji Eun Kim, Hooyeon Lee; Cancer Res Treat. 2024;56(4):1164-1170. Published online April 16, 2024; DOI: https://doi.org/10.4143/crt.2024.009

Abstract PDF Supplementary Material PubReader ePub

Purpose
The rate of interval colorectal cancer (iCRC) is now accepted as a key performance indicator of organized colorectal cancer (CRC) screening programs. We aimed to examine the association between endoscopist volumes and the rate of iCRC among individuals with a positive fecal immunochemical test (FIT) within a nationwide population-based CRC screening program.
Materials and Methods
Individuals aged ≥ 50 years who underwent colonoscopy after a positive FIT from January 1, 2019 until December 31, 2020 in the Korean National Cancer Screening Program (KNCSP) were enrolled. We converted the data into per-endoscopist screening results, calculated the iCRC rates per endoscopist, and compared them to the previous year’s annual volume that was divided into five groups (V1, 1-9; V2, 10-29; V3, 30-59; V4, 60-119; V5, ≥ 120).
Results
A total of 10,412 endoscopists performed 216,907 colonoscopies. Overall, the average rate of iCRC per endoscopist was 8.46 per 1,000 examinations. Compared with the group with the highest volume (V5 group), the rate of iCRC was 2.21 times higher in the V1 group. Similar trends were observed in the other groups (V2: relative risks [RR], 2.15; 95% confidence interval [CI], 1.57 to 2.94; V3: RR, 1.56; 95% CI, 1.15 to 2.13; V4: RR, 1.18; 95% CI, 0.83 to 1.67).
Conclusion
The findings emphasize that endoscopists with lower procedure volumes have higher risks of interval cancer being missed or undetected. To maximize the preventative impact of colonoscopy for CRC, this issue should be addressed by monitoring endoscopist volumes and variations in performances.

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Biennial Mammography Performance in the Korean National Cancer Screening Program From 2009 to 2020
Dong Jun Kim, Nan-He Yoon, Jae Kwan Jun, Mina Suh, Sunhwa Lee, Seongju Kim, Horim A. Hwang, Seung Eun Jung, Hooyeon Lee
Korean Journal of Radiology.2025;[Epub] CrossRef
Preliminary reports of lung cancer screening with low-dose computed tomography: a nationwide performance on the Korean population in 2019–2020
Horim A. Hwang, Dong Jun Kim, Nan-He Yoon, Jae Kwan Jun, Mina Suh, Sunhwa Lee, Seongju Kim, Seung Eun Jung, Hooyeon Lee
European Radiology.2025;[Epub] CrossRef

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Lung and Thoracic cancer

Intrathoracic Progression Is Still the Most Dominant Failure Pattern after First-Line Chemo-immunotherapy in Extensive-Stage Small-Cell Lung Cancer: Implications for Thoracic Radiotherapy: Dowook Kim, Hak Jae Kim, Hong-Gyun Wu, Joo Ho Lee, Suzy Kim, Tae Min Kim, Jin-Soo Kim, Byoung Hyuck Kim; Cancer Res Treat. 2024;56(2):430-441. Published online November 6, 2023; DOI: https://doi.org/10.4143/crt.2023.931

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to compare the failure patterns before and after the introduction of immunotherapy and to determine the role of thoracic radiotherapy (TRT) in extensive-stage small-cell lung cancer (ES-SCLC) treatment.
Materials and Methods
We retrospectively reviewed 294 patients with ES-SCLC, of which 62.2% underwent chemotherapy alone, 13.3% underwent chemotherapy followed by consolidative TRT (TRT group), and 24.5% underwent chemotherapy with immune checkpoint inhibitor (ICI group). We performed propensity-score matching (PSM) to compare each treatment group.
Results
The median follow-up duration was 10.4 months. At the first relapse, in the cohort showing objective response, the proportion of cases showing intrathoracic progression was significantly lower in the TRT group (37.8%) than in the chemotherapy-alone (77.2%, p < 0.001) and the ICI (60.3%, p=0.03) groups. Furthermore, in the subgroup analysis, TRT showed benefits related to intrathoracic progression-free survival (PFS) in comparison with ICI in patients with less than two involved extrathoracic sites (p=0.008) or without liver metastasis (p=0.02) or pleural metastasis (p=0.005) at diagnosis. After PSM, the TRT group showed significantly better intrathoracic PFS than both chemotherapy-alone and ICI groups (p < 0.001 and p=0.04, respectively), but showed no significant benefit in terms of PFS and overall survival in comparison with the ICI group (p=0.17 and p=0.31, respectively).
Conclusion
In ES-SCLC, intrathoracic progression was the most dominant failure pattern after immunotherapy. In the era of chemoimmunotherapy, consolidative TRT can still be considered a useful treatment strategy for locoregional control.

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Radiotherapy(R) Integration(I) Strategy for Small(S)-Cell Lung Cancer in Extensive(E) Stage (RISE) with up to 10 metastases- a study protocol of a randomized phase II trial
Łukasz Kuncman, Jacek Fijuth, Damian Tworek, Ewa Sierko, Paweł Cisek, Michał Masłowski, Maja Lisik-Habib, Magdalena Orzechowska, Katarzyna Galwas-Kliber, Adam Antczak, Izabela Chmielewska, Barbara Ziółkowska, Marta Kurczewska-Michalak, Wojciech Kuźnicki,
BMC Cancer.2025;[Epub] CrossRef
Clinical outcomes and synergistic effect between radiotherapy and immunotherapy in patients with extensive-stage small cell lung cancer: a real-world study
Meiling Sun, Huaijun Ji, Fang Deng, Jingyi Li, Ning Xu, Yu Li
BMC Cancer.2024;[Epub] CrossRef

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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.

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Lung and Thoracic cancer

Clinical Impact of Genomic and Pathway Alterations in Stage I EGFR-Mutant Lung Adenocarcinoma: Jae Seok Lee, Eun Kyung Kim, Kyung A Kim, Hyo Sup Shim; Cancer Res Treat. 2024;56(1):104-114. Published online July 24, 2023; DOI: https://doi.org/10.4143/crt.2023.728

Abstract PDF Supplementary Material PubReader ePub

Purpose
We investigated the clinical impact of genomic and pathway alterations in stage I epidermal growth factor receptor (EGFR)–mutant lung adenocarcinomas, which have a high recurrence rate despite complete surgical resection.
Materials and Methods
Out of the initial cohort of 257 patients with completely resected stage I EGFR-mutant lung adenocarcinoma, tumor samples from 105 patients were subjected to analysis using large-panel next-generation sequencing. We analyzed 11 canonical oncogenic pathways and determined the number of pathway alterations (NPA). Survival analyses were performed based on co-occurring alterations and NPA in three patient groups: all patients, patients with International Association for the Study of Lung Cancer (IASLC) pathology grade 2, and patients with recurrent tumors treated with EGFR–tyrosine kinase inhibitor (TKI).
Results
In the univariate analysis, pathological stage, IASLC grade, TP53 mutation, NPA, phosphoinositide 3-kinase pathway, p53 pathway, and cell cycle pathway exhibited significant associations with worse recurrence-free survival (RFS). Moreover, RPS6KB1 or EGFR amplifications were linked to a poorer RFS. Multivariate analysis revealed that pathologic stage, IASLC grade, and cell cycle pathway alteration were independent poor prognostic factors for RFS (p=0.002, p < 0.001, and p=0.006, respectively). In the grade 2 subgroup, higher NPA was independently associated with worse RFS (p=0.003). Additionally, in patients with recurrence treated with EGFR-TKIs, co-occurring TP53 mutations were linked to shorter progression-free survival (p=0.025).
Conclusion
Genomic and pathway alterations, particularly cell cycle alterations, high NPA, and TP53 mutations, were associated with worse clinical outcomes in stage I EGFR-mutant lung adenocarcinoma. These findings may have implications for risk stratification and the development of new therapeutic strategies in early-stage EGFR-mutant lung cancer patients.

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Stage-specific efficacy of osimertinib in treatment-naïve EGFR-mutant non-small cell lung cancer according to baseline genetic alterations in circulating tumor DNA
Yoshihiko Taniguchi, Akihiro Tamiya, Mitsuo Osuga, Shun-ichi Isa, Keiichi Nakamura, Yasuyuki Mizumori, Tsutomu Shinohara, Hidetoshi Yanai, Katsumi Nakatomi, Masahide Oki, Masahide Mori, Tomohito Kuwako, Koji Yamazaki, Masahiro Shimada, Masahiko Ando, Yasu
Investigational New Drugs.2025;[Epub] CrossRef

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Hematologic malignancy

Impact of T-Cell Engagers on COVID-19–Related Mortality in B-Cell Lymphoma Patients Receiving B-Cell Depleting Therapy: Chan Mi Lee, Pyoeng Gyun Choe, Chang Kyung Kang, Hyeon Jae Jo, Nam Joong Kim, Sung-Soo Yoon, Tae Min Kim, Wan Beom Park, Myoung-don Oh; Cancer Res Treat. 2024;56(1):324-333. Published online July 6, 2023; DOI: https://doi.org/10.4143/crt.2023.738

Abstract PDF Supplementary Material PubReader ePub

Purpose
B-cell depleting therapies, including T-cell engager (TCE), are increasingly used for patients with hematologic malignancies, including during the coronavirus disease 2019 (COVID-19) pandemic. We aimed to evaluate the relationship between TCE therapy and COVID-19–related outcomes among patients with COVID-19 and B-cell lymphomas receiving B-cell depleting therapy.
Materials and Methods
This retrospective cohort study included patients with B-cell lymphoma, who were admitted to Seoul Natio-nal University Hospital with COVID-19 between September 2021 and February 2023, and received B-cell depleting therapy before COVID-19 diagnosis. Multivariable logistic regression was used to identify factors associated with severe to critical COVID-19 and COVID-19–related mortality.
Results
Of 54 patients with B-cell lymphomas and COVID-19 who received B-cell depleting therapy, 14 were treated with TCE (TCE group) and 40 with rituximab (RTX group). COVID-19–related mortality was higher in the TCE group than in the RTX group (57.1% vs. 12.5%, p=0.002). In multivariable analyses, TCE therapy (adjusted odds ratio [aOR], 7.08; 95% confidence interval [CI], 1.29 to 38.76; p=0.024) and older age (aOR, 1.06; 95% CI, 1.00 to 1.13; p=0.035) were associated with severe to critical COVID-19. TCE therapy (aOR, 8.98; 95% CI, 1.48 to 54.40; p=0.017), older age (aOR, 1.13; 95% CI, 1.02 to 1.26; p=0.022), and prior bendamustine therapy (aOR, 7.78; 95% CI, 1.17 to 51.65; p=0.034) were independent risk factors for COVID-19–related mortality.
Conclusion
B-cell lymphoma patients treated with TCE had significantly worse outcomes from COVID-19 than those treated with RTX. TCE therapy should be used with caution in B-cell lymphoma patients during the COVID-19 epidemic.

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Long-Term Outcomes of COVID-19 and Risk Factors for Prolonged or Persistent COVID-19 in Lymphoma Patients: A Multicenter, Retrospective Cohort Study
Jung Ah Lee, Min Han, Sangmin Ahn, Yongseop Lee, Joon-Sup Yeom, Jun Yong Choi, Nam Su Ku, Su Jin Jeong, Jung Ho Kim, Jin Seok Kim, Haerim Chung, Hyunsoo Cho, Yu Ri Kim, Jin Young Ahn
Journal of Korean Medical Science.2024;[Epub] CrossRef
Features of the T-cell immune response in patients with hematological diseases after SARS-CoV-2 infection and vaccination
K. V. Zornikova, N. O. Ivanova, O. A. Aleshina, S. A. Sheetikov, V. D. Davydova, A. V. Bogolyubova
Russian journal of hematology and transfusiology.2024; 69(2): 200. CrossRef
Call for Balancing the Risks and Benefits of Immunotherapeutic Agents for Lymphoma during the COVID-19 Pandemic
Chan Mi Lee, Wan Beom Park
Infection & Chemotherapy.2024; 56(3): 406. CrossRef
Epcoritamab in relapsed/refractory large B-cell lymphoma: 2-year follow-up from the pivotal EPCORE NHL-1 trial
Catherine Thieblemont, Yasmin H. Karimi, Herve Ghesquieres, Chan Y. Cheah, Michael Roost Clausen, David Cunningham, Wojciech Jurczak, Young Rok Do, Robin Gasiorowski, David John Lewis, Tae Min Kim, Marjolein van der Poel, Michelle Limei Poon, Tatyana Feld
Leukemia.2024; 38(12): 2653. CrossRef

3,519 View
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4 Crossref

Head and Neck cancer

Outcomes of Salvage Therapy for Oropharyngeal Cancer Recurrence Following Upfront Radiation Therapy and Prognostic Factors: Nayeon Choi, Hack Jung Kim, Heejun Yi, Heejung Kim, Tae Hwan Kim, Han-Sin Jeong, Young-Ik Son, Chung-Hwan Baek, Dongryul Oh, Yong Chan Ahn, Man Ki Chung; Cancer Res Treat. 2023;55(4):1123-1133. Published online May 8, 2023; DOI: https://doi.org/10.4143/crt.2022.1046

Abstract PDF PubReader ePub

Purpose
This study aimed to investigate the oncologic outcomes and prognostic factors of salvage treatments in patients with recurrent oropharyngeal squamous cell carcinoma (OPSCC) after radiotherapy (RT)-based treatment.
Materials and Methods
A cancer registry was used to retrieve the records of 337 patients treated with definitive RT or concurrent chemoradiotherapy (CRT) from 2008 to 2018 at a single institution. The poor-responder group (PRG) was defined as patients with residual or recurrent disease after primary treatment, and the oncologic outcomes for each salvage treatment method were analyzed. In addition, prognostic indicators of recurrence-free survival (RFS) and overall survival (OS) were identified in patients who underwent salvage treatment.
Results
After initial (C)RT, the PRG comprised 71 of the 337 patients (21.1%): 18 patients had residual disease, and 53 had recurrence after primary treatment (mean time to recurrence 19.5 months). Of these, 63 patients received salvage treatment (surgery 57.2%, re-(C)RT 23.8%, and chemotherapy 19.0%), and the salvage success rate was 47.6% at the last follow-up. The overall 2-year OS for salvage treatments was 56.4% (60.8% for the salvage surgery group and 46.2% for the salvage re-(C)RT). Salvage surgery patients with negative resection margins had better oncologic outcomes than those with close/positive resection margins. Using multivariate analyses, locoregional recurrence and residual disease after primary surgery were associated with poor outcome after salvage treatment. In Kaplan-Meier analyses, p16 status was significantly associated with OS in the initial treatment setting but not in the salvage setting.
Conclusion
In recurrent OPSCC after RT-based treatment, successful salvage was achieved in 56.4% patients who had undergone salvage surgery and radiation treatment. Salvage treatment methods should be selected carefully, given recurrence site as a prognostic factor for RFS.

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Toxicities and prognostic factors in elderly HPV‐associated oropharyngeal cancer patients treated with radiotherapy or chemoradiotherapy
Erkan Topkan, Efsun Somay, Ugur Selek
Journal of Medical Virology.2024;[Epub] CrossRef

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Gastrointestinal cancer

Analysis of Plasma Circulating Tumor DNA in Borderline Resectable Pancreatic Cancer Treated with Neoadjuvant Modified FOLFIRINOX: Clinical Relevance of DNA Damage Repair Gene Alteration Detection: Dong-Hoon Lim, Hyunseok Yoon, Kyu-pyo Kim, Baek-Yeol Ryoo, Sang Soo Lee, Do Hyun Park, Tae Jun Song, Dae Wook Hwang, Jae Hoon Lee, Ki Byung Song, Song Cheol Kim, Seung-Mo Hong, Jaewon Hyung, Changhoon Yoo; Cancer Res Treat. 2023;55(4):1313-1320. Published online May 4, 2023; DOI: https://doi.org/10.4143/crt.2023.452

Abstract PDF Supplementary Material PubReader ePub

Purpose
There are no reliable biomarkers to guide treatment for patients with borderline resectable pancreatic cancer (BRPC) in the neoadjuvant setting. We used plasma circulating tumor DNA (ctDNA) sequencing to search biomarkers for patients with BRPC receiving neoadjuvant mFOLFIRINOX in our phase 2 clinical trial (NCT02749136).
Materials and Methods
Among the 44 patients enrolled in the trial, patients with plasma ctDNA sequencing at baseline or post-operation were included in this analysis. Plasma cell-free DNA isolation and sequencing were performed using the Guardant 360 assay. Detection of genomic alterations, including DNA damage repair (DDR) genes, were examined for correlations with survival.
Results
Among the 44 patients, 28 patients had ctDNA sequencing data qualified for the analysis and were included in this study. Among the 25 patients with baseline plasma ctDNA data, 10 patients (40%) had alterations of DDR genes detected at baseline, inclu-ding ATM, BRCA1, BRCA2 and MLH1, and showed significantly better progression-free survival than those without such DDR gene alterations detected (median, 26.6 vs. 13.5 months; log-rank p=0.004). Patients with somatic KRAS mutations detected at baseline (n=6) had significantly worse overall survival (median, 8.5 months vs. not applicable; log-rank p=0.003) than those without. Among 13 patients with post-operative plasma ctDNA data, eight patients (61.5%) had detectable somatic alterations.
Conclusion
Detection of DDR gene mutations from plasma ctDNA at baseline was associated with better survival outcomes of pati-ents with borderline resectable pancreatic ductal adenocarcinoma treated with neoadjuvant mFOLFIRINOX and may be a prognostic biomarker.

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A Review of Circulating Tumor DNA (ctDNA) in Pancreatic Cancer: Ready for the Clinic?
Purvi Jonnalagadda, Virginia Arnold, Benjamin A. Weinberg
Journal of Gastrointestinal Cancer.2025;[Epub] CrossRef
A Practical Approach to Interpreting Circulating Tumor DNA in the Management of Gastrointestinal Cancers
Zexi Allan, David S Liu, Margaret M Lee, Jeanne Tie, Nicholas J Clemons
Clinical Chemistry.2024; 70(1): 49. CrossRef
High somatic mutations in circulating tumor DNA predict response of metastatic pancreatic ductal adenocarcinoma to first-line nab-paclitaxel plus S-1: prospective study
Lei Huang, Yao Lv, Shasha Guan, Huan Yan, Lu Han, Zhikuan Wang, Quanli Han, Guanghai Dai, Yan Shi
Journal of Translational Medicine.2024;[Epub] CrossRef
Decoding the Dynamics of Circulating Tumor DNA in Liquid Biopsies
Khadija Turabi, Kelsey Klute, Prakash Radhakrishnan
Cancers.2024; 16(13): 2432. CrossRef
Building on the clinical applicability of ctDNA analysis in non-metastatic pancreatic ductal adenocarcinoma
Ibone Labiano, Ana E. Huerta, Maria Alsina, Hugo Arasanz, Natalia Castro, Saioa Mendaza, Arturo Lecumberri, Iranzu Gonzalez-Borja, David Guerrero-Setas, Ana Patiño-Garcia, Gorka Alkorta-Aranburu, Irene Hernández-Garcia, Virginia Arrazubi, Elena Mata, Davi
Scientific Reports.2024;[Epub] CrossRef
Liquid biopsy analysis of lipometabolic exosomes in pancreatic cancer
Wei Guo, Peiyao Ying, Ruiyang Ma, Zuoqian Jing, Gang Ma, Jin Long, Guichen Li, Zhe Liu
Cytokine & Growth Factor Reviews.2023; 73: 69. CrossRef

4,034 View
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6 Crossref

The Role of Adjuvant Chemotherapy after Neoadjuvant Chemoradiotherapy Followed by Surgery in Patients with Esophageal Squamous Cell Carcinoma: Seong Yong Park, Hong Kwan Kim, Yeong Jeong Jeon, Junghee Lee, Jong Ho Cho, Yong Soo Choi, Young Mog Shim, Jae Il Zo; Cancer Res Treat. 2023;55(4):1231-1239. Published online April 24, 2023; DOI: https://doi.org/10.4143/crt.2022.1417

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to investigate the efficacy of adjuvant chemotherapy after neoadjuvant chemoradiotherapy (CCRTx) followed by surgery in patients with esophageal squamous cell carcinoma (ESCC).
Materials and Methods
We retrospectively analyzed the data from 382 patients who received neoadjuvant CCRTx and esophagectomy for ESCC between 2003 and 2018.
Results
This study included 357 (93.4%) men, and the years median patient age was 63 (range, 40 to 84 years). Overall, 69 patients (18.1%) received adjuvant chemotherapy, whereas 313 patients (81.9%) did not. The median follow-up period was 28.07 months (interquartile range, 15.50 to 62.59). The 5-year overall survival (OS) and disease-free survival were 47.1% and 42.6%, respectively. Adjuvant chemotherapy did not improve OS in all patients, but subgroup analysis revealed that adjuvant chemotherapy improved the 5-year OS in patients with ypT+N+ (24.8% vs. 29.9%, p=0.048), whereas the survival benefit of adjuvant chemotherapy was not observed in patients with ypT0N0, ypT+N0, or ypT0N+. Multivariable analysis revealed that ypStage and adjuvant chemotherapy (hazard ratio, 0.601; p=0.046) were associated with OS in patients with ypT+N+. Freedom from distant metastasis was marginally different according to the adjuvant chemotherapy (48.3% vs. 41.3%, p=0.141).
Conclusion
Adjuvant chemotherapy after neoadjuvant therapy followed by surgery reduces the distant metastasis in ypT+N+ ESCC patients, thereby improving the OS. The consideration could be given to administration of adjuvant chemotherapy to ypT+N+ ESCC patients with tolerable conditions.

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Adjuvant therapy provides no additional recurrence-free benefit for esophageal squamous cell carcinoma patients after neoadjuvant chemoimmunotherapy and surgery: a multi-center propensity score match study
Shu-Han Xie, Li-Tao Yang, Hai Zhang, Zi-Lu Tang, Zhi-Wei Lin, Yi Chen, Zhi-Nuan Hong, Rong-Yu Xu, Wan-Li Lin, Ming-Qiang Kang
Frontiers in Immunology.2024;[Epub] CrossRef
Clinical implications of C-reactive protein–albumin–lymphocyte (CALLY) index in patients with esophageal cancer
Ruiya Ma, Yoshinaga Okugawa, Tadanobu Shimura, Shinji Yamashita, Yuhki Sato, Chengzeng Yin, Ryo Uratani, Takahito Kitajima, Hiroki Imaoka, Mikio Kawamura, Yuhki Morimoto, Yoshiki Okita, Shigeyuki Yoshiyama, Masaki Ohi, Yuji Toiyama
Surgical Oncology.2024; 53: 102044. CrossRef
Adjuvant immunotherapy after neoadjuvant immunochemotherapy and esophagectomy for esophageal squamous cell carcinoma: a real-world study
Jifeng Feng, Liang Wang, Xun Yang, Qixun Chen
Frontiers in Immunology.2024;[Epub] CrossRef

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3 Crossref

Lung and Thoracic cancer

MLL4 Regulates the Progression of Non–Small-Cell Lung Cancer by Regulating the PI3K/AKT/SOX2 Axis: Yang Yang, Rongfang Qiu, Qiaoyou Weng, Ziwei Xu, Jingjing Song, Siyu Zhao, Miaomiao Meng, Dengke Zhang, Chunli Kong, Hailin Wang, Min Xu, Zhongwei Zhao, Jiansong Ji; Cancer Res Treat. 2023;55(3):778-803. Published online January 26, 2023; DOI: https://doi.org/10.4143/crt.2022.1042

Abstract PDF Supplementary Material PubReader ePub

Purpose
Mixed-lineage leukemia protein 4 (MLL4/KMT2D) is a histone methyltransferase, and its mutation has been reported to be associated with a poor prognosis in many cancers, including lung cancer. We investigated the function of MLL4 in lung carcinogenesis.
Materials and Methods
RNA sequencing (RNA-seq) in A549 cells transfected with control siRNA or MLL4 siRNA was performed. Also, we used EdU incorporation assay, colony formation assays, growth curve analysis, transwell invasion assays, immunohistochemical staining, and in vivo bioluminescence assay to investigate the function of MLL4 in lung carcinogenesis.
Results
We found that MLL4 expression was downregulated in non–small cell lung cancer (NSCLC) tissues compared to adjacent normal tissues and tended to decrease with disease stage progression. We analyzed the transcriptomes in control and MLL4- deficient cells using high-throughput RNA deep sequencing (RNA-seq) and identified a cohort of target genes, such as SOX2, ATF1, FOXP4, PIK3IP1, SIRT4, TENT5B, and LFNG, some of which are related to proliferation and metastasis. Our results showed that low expression of MLL4 promotes NSCLC cell proliferation and metastasis and is required for the maintenance of NSCLC stem cell properties.
Conclusion
Our findings identify an important role of MLL4 in lung carcinogenesis through transcriptional regulation of PIK3IP1, affecting the PI3K/AKT/SOX2 axis, and suggest that MLL4 could be a potential prognostic indicator and target for NSCLC therapy.

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Role and potential therapeutic value of histone methyltransferases in drug resistance mechanisms in lung cancer
Linxiang Zhang, Xueying Zhang, Yan Shi, Yuhan Ni, Jiaojiao Fei, Zhixin Jin, Wenjuan Li, Xiaojing Wang, Nan Wu
Frontiers in Oncology.2024;[Epub] CrossRef
The multifaceted role of SOX2 in breast and lung cancer dynamics
Kiavash Hushmandi, Seyed Hassan Saadat, Seyedalireza Mirilavasani, Salman Daneshi, Amir Reza Aref, Noushin Nabavi, Rasoul Raesi, Afshin Taheriazam, Mehrdad Hashemi
Pathology - Research and Practice.2024; 260: 155386. CrossRef
PIK3IP1: structure, aberration, function, and regulation in diseases
Yingjie Jia, Pengxing He, Xubin Ma, Kaili Lv, Ying Liu, Yichao Xu
European Journal of Pharmacology.2024; 977: 176753. CrossRef
UBQLN4 promotes the proliferation and invasion of non-small cell lung cancer cell by regulating PI3K/AKT pathway
Li He, Heng Chen, Bin Ruan, Li He, Ming Luo, Yulun Fu, Rui Zou
Journal of Cancer Research and Clinical Oncology.2024;[Epub] CrossRef
Role of histone methyltransferase KMT2D in BMSC osteogenesis via AKT signaling
Zhichun Zhang, Yanyan Guo, Xuejun Gao, Xiaoyan Wang, Chanyuan Jin
Regenerative Therapy.2024; 26: 775. CrossRef
Landscape of targeted therapies for lung squamous cell carcinoma
Qiuxuan Chen, Xiaoshuo Zheng, Weiting Cheng, Jian Li
Frontiers in Oncology.2024;[Epub] CrossRef

4,862 View
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6 Crossref

Breast cancer

Impact of Postmastectomy Radiation Therapy on Breast Cancer Patients According to Pathologic Nodal Status after Modern Neoadjuvant Chemotherapy: Dowook Kim, Jin Ho Kim, In Ah Kim, Ji Hyun Chang, Kyung Hwan Shin; Cancer Res Treat. 2023;55(2):592-602. Published online October 11, 2022; DOI: https://doi.org/10.4143/crt.2022.998

Abstract PDF Supplementary Material PubReader ePub

Purpose
The utility of postmastectomy radiation therapy (PMRT) for breast cancer patients after neoadjuvant chemotherapy (NAC) is highly controversial. This study evaluated the impact of PMRT according to pathologic nodal status after modern NAC.
Materials and Methods
We retrospectively reviewed 682 patients with clinical stage II-III breast cancer who underwent NAC and mastectomy from 2013 to 2017. In total, 596 patients (87.4%) received PMRT, and 86 (12.6%) did not. We investigated the relationships among locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), overall survival (OS), and various prognostic factors. Subgroup analyses were also performed to identify patients who may benefit from PMRT.
Results
The median follow-up duration was 67 months. In ypN+ patients (n=368, 51.2%), PMRT showed significant benefits in terms of LRRFS, DFS, and OS (all p < 0.001). In multivariate analyses, histologic grade (HG) III (p=0.002), lymphovascular invasion (LVI) (p=0.045), and ypN2-3 (p=0.02) were significant risk factors for poor LRRFS. In ypN1 patients with more than two prognostic factors among luminal/human epidermal growth factor receptor-2–negative subtype, HG I-II, and absence of LVI, PMRT had no significant effect on LRRFS (p=0.18). In ypN0 patients (n=351, 48.8%), PMRT was not significantly associated with LRRFS, DFS, or OS. However, PMRT showed better LRRFS in triple-negative breast cancer (TNBC) patients (p=0.03).
Conclusion
PMRT had a major impact on treatment outcomes in patients with residual lymph nodes following NAC and mastectomy. Among ypN0 patients, PMRT may be beneficial only for those with TNBC.

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Analysis of Individualized Silicone Rubber Bolus Using Fan Beam Computed Tomography in Postmastectomy Radiotherapy: A Dosimetric Evaluation and Skin Acute Radiation Dermatitis Survey
Xue-mei Chen, Chen-di Xu, Li-ping Zeng, Xiao-tong Huang, Ao-qiang Chen, Lu Liu, Liu-wen Lin, Le-cheng Jia, Hua Li, Xiao-bo Jiang
Technology in Cancer Research & Treatment.2024;[Epub] CrossRef
Does Post-Mastectomy Radiotherapy Confer Survival Benefits on Patients With 1-3 Clinically Positive Lymph Nodes Rendered Pathologically Negative After Neoadjuvant Systemic Chemotherapy: Consensus from A Pooled Analysis?
Munaser Alamoodi
European Journal of Breast Health.2024; 20(2): 81. CrossRef
Oncological outcomes of stage I–II breast cancer treatment after subcutaneous/skin-sparing mastectomies with reconstruction
E. A. Rasskazova, A. D. Zikiryakhodzhaev
MD-Onco.2024; 4(3): 37. CrossRef
Effectiveness of mat pilates on fatigue in women with breast cancer submitted to adjuvant radiotherapy: randomized controlled clinical trial
Daniele Medeiros Torres, Kelly de Menezes Fireman, Erica Alves Nogueira Fabro, Luiz Claudio Santos Thuler, Rosalina Jorge Koifman, Anke Bergmann, Sabrina da Silva Santos
Supportive Care in Cancer.2023;[Epub] CrossRef
The Role of Sentinel Lymph Node Biopsy in Breast Cancer Patients Who Become Clinically Node-Negative Following Neo-Adjuvant Chemotherapy: A Literature Review
Giulia Ferrarazzo, Alberto Nieri, Emma Firpo, Andrea Rattaro, Alessandro Mignone, Flavio Guasone, Augusto Manzara, Giuseppe Perniciaro, Stefano Spinaci
Current Oncology.2023; 30(10): 8703. CrossRef

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Gastrointestinal cancer

Descriptive Analysis of Gastric Cancer Mortality in Korea, 2000-2020: Tung Hoang, Hyeongtaek Woo, Sooyoung Cho, Jeeyoo Lee, Sayada Zartasha Kazmi, Aesun Shin; Cancer Res Treat. 2023;55(2):603-617. Published online September 6, 2022; DOI: https://doi.org/10.4143/crt.2022.307

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to examine secular trends, age-period-cohort effects, and geographical differences in gastric cancer (GC) mortality in Korea.
Materials and Methods
Using cause of death data from the Korean Statistical Information Service for GC from 2000 to 2020, we calculated average annual percentage changes (AAPCs) in the age-standardized mortality of GC in 17 cities and provinces through joinpoint regression. Decomposition of age, period, and cohort effects on GC mortality were elucidated by applying a log-linear model and an intrinsic estimate method. Spatial patterns and the degree of spatial clustering in 250 administrative regions were explored via Moran’s I statistics. Stratification by sex was performed for all analyses.
Results
The age-standardized mortality of GC per 100,000 persons declined from 29.0 in 2000 to 7.9 in 2020 (AAPC, -6.28%). Age-period-cohort analyses of GC mortality showed a downward trend among five-year age groups from age 20-89 years across five-year periods from 2005-2020 and five-year birth cohorts from 1920-2000. Overall, the younger birth cohort showed lower mortality rates than the older cohort within the same period. In 2020, clusters of high GC mortality were observed in the central area for men (Chungcheongbuk, Jeollabuk, Gyeongsangbuk, and Gyeongsangnam) and in the eastern area for women (Gyeongsangbuk).
Conclusion
This study identified a downward trend in GC mortality among men and women from 2000 to 2020 in Korea. This trend was mainly attributed to birth cohort rather than period effects. Spatial analysis showed high GC mortality in the Chungcheong and Gyeongsangbuk areas.

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Efficacy and safety of herbal medicine treatment on postsurgical recovery in gastric cancer patients: A systematic review and meta-analysis
Soo-Dam Kim, Sook-Jin Pyo, Dong-Hyeon Kim, Hwa-Seung Yoo, So-Jung Park
Medicine.2025; 104(1): e41034. CrossRef
Expression of claudin 18.2 in poorly cohesive carcinoma and its association with clinicopathologic parameters in East Asian patients
Moonsik Kim, Byung Woog Kang, Jihyun Park, Jin Ho Baek, Jong Gwang Kim
Pathology - Research and Practice.2024; 263: 155628. CrossRef
Updated Epidemiology of Gastric Cancer in Asia: Decreased Incidence but Still a Big Challenge
Wing Sum Shin, Fuda Xie, Bonan Chen, Peiyao Yu, Jun Yu, Ka Fai To, Wei Kang
Cancers.2023; 15(9): 2639. CrossRef

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Pediatric cancer

The Efficacy of Alternate Systemic Intravenous Chemotherapy and Intra-arterial Chemotherapy Approach for Eye Globe Salvage in Retinoblastoma: Jung Woo Han, Christopher Seungkyu Lee, Seung Min Hahn, Won Kee Ahn, Hyo Sun Kim, Hyeseon Yun, Sung Chul Lee, Byung Moon Kim, Dong Joon Kim, Chuhl Joo Lyu; Cancer Res Treat. 2023;55(1):270-278. Published online May 24, 2022; DOI: https://doi.org/10.4143/crt.2021.1537

Abstract PDF Supplementary Material PubReader ePub

Purpose
The advances in the treatment of retinoblastoma have enabled salvaging the globe in advanced stages with intra-arterial chemotherapy (IAC). We developed a strategy of alternate application of systemic intravenous chemotherapy (IVC) and IAC (referred to as alternate systemic IVC and IAC; ASIAC) to reduce central nervous metastases during IAC and examined its efficacy and safety in eye globe salvage in this study.
Materials and Methods
Between January 2010 and February 2021, 43 eyes of 40 patients received ASIAC treatment for retinoblastoma at the Yonsei Cancer Center, Yonsei University Health System. Their medical records were reviewed retrospectively to evaluate the eye salvage rate (ESR), defined from diagnosis to enucleation. High-risk retinoblastoma was defined as group D or E by the International Classification of Retinoblastoma.
Results
The study enrolled 38 and five cases of high-risk and low-risk retinoblastoma, respectively. In total, 178 IAC and 410 IVC courses were administered, with a median of 4 (interquartile range [IQR], 3.0 to 5.0) IAC and 9 (IQR, 6.0 to 11) IVC courses per eye, respectively. The 5-year ESR was 60.4%±8.7% for the whole cohort, 100% for low-risk retinoblastoma, and 53.6%±9.8% for high-risk retinoblastoma. Among those diagnosed since 2015, the 5-year ESR for high-risk retinoblastoma was 63.5%±14.0%. Fifteen eyes underwent enucleation; no viable tumor was found in three enucleated eyes. There were no deaths in this cohort.
Conclusion
Primary IAC-IVC (i.e., ASIAC) for patients with retinoblastoma was tolerable and effective in salvaging the eye and maintaining survival.

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Selective ophthalmic arterial injection using a balloon catheter for retinoblastoma: a seven-year clinical evaluation
Sota Oguro, Yi Ning Chen, Takashi Yamane, Makoto Mohri, Shigenobu Suzuki
Japanese Journal of Ophthalmology.2024; 68(4): 346. CrossRef
Hematological Second Primary Malignancy in Pediatric Retinoblastoma: A Case Report and Systematic Review
Seung Hyun Park, Hyun Young Park, Heejin Kim, Jung Woo Han, Jin Sook Yoon
Ophthalmic Plastic & Reconstructive Surgery.2024; 40(5): 487. CrossRef

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Gastrointestinal cancer

Molecular and Immune Profiling of Syngeneic Mouse Models Predict Response to Immune Checkpoint Inhibitors in Gastric Cancer: Dagyeong Lee, Junyong Choi, Hye Jeong Oh, In-Hye Ham, Sung Hak Lee, Sachiyo Nomura, Sang-Uk Han, Hoon Hur; Cancer Res Treat. 2023;55(1):167-178. Published online May 20, 2022; DOI: https://doi.org/10.4143/crt.2022.094

Abstract PDF Supplementary Material PubReader ePub

Purpose
Appropriate preclinical mouse models are needed to evaluate the response to immunotherapeutic agents. Immunocompetent mouse models have rarely been reported for gastric cancer. Thus, we investigated immunophenotypes and responses to immune checkpoint inhibitor (ICI) in immunocompetent mouse models using various murine gastric cancer cell lines.
Materials and Methods
We constructed subcutaneous syngeneic tumors with murine gastric cancer cell lines, YTN3 and YTN16, in C57BL/6J mice. Mice were intraperitoneally treated with IgG isotype control or an anti–programmed death-ligand 1 (PD-L1) neutralizing antibody. We used immunohistochemistry to evaluate the tumor-infiltrating immune cells of formalin-fixed paraffin-embedded mouse tumor tissues. We compared the protein and RNA expression between YTN3 and YTN16 cell lines using a mouse cytokine array and RNA sequencing.
Results
The mouse tumors revealed distinct histological and molecular characteristics. YTN16 cells showed upregulation of genes and proteins related to immunosuppression, such as Ccl2 (CCL2) and Csf1 (M-CSF). Macrophages and exhausted T cells were more enriched in YTN16 tumors than in YTN3 tumors. Several YTN3 tumors were completely regressed by the PD-L1 inhibitor, whereas YTN16 tumors were unaffected. Although treatment with a PD-L1 inhibitor increased infiltration of T cells in both the tumors, the proportion of exhausted immune cells did not decrease in the non-responder group.
Conclusion
We confirmed the histological and molecular features of cancer cells with various responses to ICI. Our models can be used in preclinical research on ICI resistance mechanisms to enhance clinical efficacy.

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Tubulointerstitial nephritis antigen-like 1 from cancer-associated fibroblasts contribute to the progression of diffuse-type gastric cancers through the interaction with integrin β1
Dagyeong Lee, In-Hye Ham, Hye Jeong Oh, Dong Min Lee, Jung Hwan Yoon, Sang-Yong Son, Tae-Min Kim, Jae-Young Kim, Sang-Uk Han, Hoon Hur
Journal of Translational Medicine.2024;[Epub] CrossRef
Safety and Efficacy of Neoadjuvant Chemoimmunotherapy in Gastric Cancer Patients with a PD-L1 Positive Status: A Case Report
Alexandra V. Avgustinovich, Olga V. Bakina, Sergey G. Afanas’ev, Liudmila V. Spirina, Alexander M. Volkov
Current Issues in Molecular Biology.2023; 45(9): 7642. CrossRef
Targeting GAS6/AXL signaling improves the response to immunotherapy by restoring the anti-immunogenic tumor microenvironment in gastric cancer
Tae Hoon Kim, Dagyeong Lee, Hye Jeong Oh, In-Hye Ham, Dong Min Lee, Yulim Lee, Zhang Zhang, Ding Ke, Hoon Hur
Life Sciences.2023; 335: 122230. CrossRef

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Gynecologic cancer

Genomic Correlates of Unfavorable Outcome in Locally Advanced Cervical Cancer Treated with Neoadjuvant Chemoradiation: Yuchun Wei, Chuqing Wei, Liang Chen, Ning Liu, Qiuxiang Ou, Jiani C. Yin, Jiaohui Pang, Zhenhao Fang, Xue Wu, Xiaonan Wang, Dianbin Mu, Yang Shao, Jinming Yu, Shuanghu Yuan; Cancer Res Treat. 2022;54(4):1209-1218. Published online January 17, 2022; DOI: https://doi.org/10.4143/crt.2021.963

Abstract PDF Supplementary Material PubReader ePub

Purpose
Neoadjuvant therapy modality can increase the operability rate and mitigate pathological risks in locally advanced cervical cancer, but treatment response varies widely. It remains unclear whether genetic alterations correlate with the response to neoadjuvant therapy and disease-free survival (DFS) in locally advanced cervical cancer.
Materials and Methods
A total of 62 locally advanced cervical cancer (stage IB-IIA) patients who received neoadjuvant chemoradiation plus radical hysterectomy were retrospectively analyzed. Patients’ tumor biopsy samples were comprehensively profiled using targeted next generation sequencing. Pathologic response to neoadjuvant treatment and DFS were evaluated against the association with genomic traits.
Results
Genetic alterations of PIK3CA were most frequent (37%), comparable to that of Caucasian populations from The Cancer Genome Atlas. The mutation frequency of genes including TERT, POLD1, NOS2, and FGFR3 was significantly higher in Chinese patients whereas RPTOR, EGFR, and TP53 were underrepresented in comparison to Caucasians. Germline mutations were identified in 21% (13/62) of the cohort and more than half (57%) had mutations in DNA damage repair genes, including BRCA1/2, TP53 and PALB2. Importantly, high tumor mutation burden, TP53 polymorphism (rs1042522), and KEAP1 mutations were found to be associated with poor pathologic response to neoadjuvant chemoradiation treatment. KEAP1 mutations, PIK3CA-SOX2 co-amplification, TERC copy number gain, and TYMS polymorphism correlated with an increased risk of disease relapse.
Conclusion
We report the genomic profile of locally advanced cervical cancer patients and the distinction between Asian and Caucasian cohorts. Our findings highlight genomic traits associated with unfavorable neoadjuvant chemoradiation response and a higher risk of early disease recurrence.

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Comprehensive characterization of PKHD1 mutation in human colon cancer
Lu Han, Fangming Gong, Xuxiaochen Wu, Wanxiangfu Tang, Hua Bao, Yue Wang, Daizhenru Wang, Yulan Sun, Peng Li
Cancer Medicine.2024;[Epub] CrossRef
PBRM1 presents a potential ctDNA marker to monitor response to neoadjuvant chemotherapy in cervical cancer
Wenhan Li, Yuhui Huang, Man Xiao, Jing Zhao, Shi Du, Zehua Wang, Sha Hu, Lu Yang, Jing Cai
iScience.2024; 27(3): 109160. CrossRef
Comprehensive genomic profiling of pulmonary spindle cell carcinoma using tissue and plasma samples: insights from a real‐world cohort analysis
Yi Sun, Shilei Qin, Song Wang, Jiaohui Pang, Qiuxiang Ou, Weiquan Liang, Hai Zhong
The Journal of Pathology: Clinical Research.2024;[Epub] CrossRef
PD-1 inhibitor plus concurrent chemoradiotherapy for high-risk locally advanced cervical cancer
Cong Wang, Lijun Liu, Xia Li, Jia Lei, Yiqian Li, Zhibo Shen, Huirong Shi, Yan Cheng
Future Oncology.2024; 20(20): 1415. CrossRef
A biomarker exploration in small-cell lung cancer for brain metastases risk and prophylactic cranial irradiation therapy efficacy
Li Li, Ning Liu, Tao Zhou, Xueting Qin, Xiaoyu Song, Song Wang, Jiaohui Pang, Qiuxiang Ou, Yong Wang, Dexian Zhang, Jiaran Li, Fuhao Xu, Shuming Shi, Jinming Yu, Shuanghu Yuan
Lung Cancer.2024; 196: 107959. CrossRef
Prospects of POLD1 in Human Cancers: A Review
Michał Gola, Przemysław Stefaniak, Janusz Godlewski, Barbara Jereczek-Fossa, Anna Starzyńska
Cancers.2023; 15(6): 1905. CrossRef
Copy-number-gain of telomerase reverse transcriptase (hTERT) is associated with an unfavorable prognosis in esophageal adenocarcinoma
Su Ir Lyu, Felix C. Popp, Adrian Georg Simon, Anne Maria Schultheis, Thomas Zander, Caroline Fretter, Wolfgang Schröder, Christiane J. Bruns, Thomas Schmidt, Alexander Quaas, Karl Knipper
Scientific Reports.2023;[Epub] CrossRef

7,524 View
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Gastrointestinal cancer

Role of Esophagectomy after Chemoradiation Therapy in Patients with Locally Advanced Squamous Cell Carcinoma: A Comparative Analysis Stratified by Clinical Response to Chemoradiation Therapy: Jesang Yu, Jong Hoon Kim, Sung-Bae Kim, Sook Ryun Park, Young-Hee Kim, Hyeong Ryul Kim, Hyun Joo Lee, Ho June Song, Kye Jin Song, Jeong Yun Jang, Yoon Young Jo, Ye Jin Yoo; Cancer Res Treat. 2022;54(4):1148-1156. Published online December 20, 2021; DOI: https://doi.org/10.4143/crt.2021.885

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to evaluate the long-term effect of esophagectomy in patients with esophageal squamous cell carcinoma (ESCC) by comparing the chemoradiotherapy (CRT)-only group and the trimodality treatment (TMT) group who received concurrent CRT followed by surgery.
Materials and Methods
We included 412 operable ESCC patients treated with TMT or CRT between January 2005 and December 2015. The oncological outcomes of the two groups were compared using a weighted Cox proportional-hazards model with inverse probability of treatment weighting (IPTW).
Results
The median survival time was 64 and 32 months in the TMT (n=270) and CRT (n=142) groups, respectively (p < 0.001). After IPTW, the median overall survival (OS) remained significantly higher in the TMT group than in the CRT group (61 months vs. 32 months, p=0.016). Moreover, the TMT group showed a better local recurrence-free rate (LRFR, p < 0.001) and distant metastasis-free rate (p=0.007). In the subgroup of patients with clinical complete response (cCR), the OS was not significantly different between the two groups, both before and after IPTW adjustment (p=0.35 and p=0.93). However, among non-cCR patients, the OS was significantly higher in the TMT group (64% vs. 45%, p < 0.001).
Conclusion
In patients with locally advanced ESCC, TMT was superior to CRT in terms of OS and LRFR. Such difference was more prominent in the non-cCR subgroup. In patients who achieved cCR, esophagectomy was effective in improving LRFR but not OS, suggesting that esophagectomy may be omitted in complete responders.

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Comparison of esophageal cancer survival after neoadjuvant chemoradiotherapy plus surgery versus definitive chemoradiotherapy: A systematic review and meta-analysis
Junli Ke, Yujie Xie, Shenyang Huang, Wei Wang, Zhengang Zhao, Wanli Lin
Asian Journal of Surgery.2024; 47(9): 3827. CrossRef
Multi-disciplinary management of esophageal carcinoma: Current practices and future directions
Chanyoot Bandidwattanawong
Critical Reviews in Oncology/Hematology.2024; 197: 104315. CrossRef
Practice pattern and risk of not receiving planned surgery after neoadjuvant chemoradiotherapy for locally advanced oesophageal squamous cell carcinoma
Tae Hee Hong, Tae Ho Kim, Genehee Lee, Jeonghee Yun, Yeong Jeong Jeon, Junghee Lee, Sumin Shin, Seong Yong Park, Jong Ho Cho, Yong Soo Choi, Young Mog Shim, Jong-Mu Sun, Dongryul Oh, Hong Kwan Kim
European Journal of Cardio-Thoracic Surgery.2024;[Epub] CrossRef
Induction Therapy of Tislelizumab Combined with Cisplatin and 5-Fluorouracil and Subsequent Conversion Surgery in Patients with Unresectable Advanced Esophageal Squamous Cell Carcinoma: A Phase 2, Single Center Study
Tongpeng Xu, Jianan Bai, Kun Zhao, Xiaofeng Chen, Shuhui Wang, Shusheng Zhu, Chongqi Sun, Chenhui Zhao, Ting Wang, Ling Zhu, Meizhen Hu, Fei Pang, Junling Zhang, Wei Wang, Yongqian Shu, Fang Li, Yue Zhou
Annals of Surgical Oncology.2024; 31(13): 9321. CrossRef
Unveiling Therapeutic Targets for Esophageal Cancer: A Comprehensive Review
Rakesh Acharya, Ananya Mahapatra, Henu Kumar Verma, L. V. K. S. Bhaskar
Current Oncology.2023; 30(11): 9542. CrossRef
Nomogram for predicting pathologic complete response following preoperative chemoradiotherapy in patients with esophageal squamous cell carcinoma
Young Seob Shin, Jeong Yun Jang, Ye Jin Yoo, Jesang Yu, Kye Jin Song, Yoon Young Jo, Sung-Bae Kim, Sook Ryun Park, Ho June Song, Yong-Hee Kim, Hyeong Ryul Kim, Jong Hoon Kim
Gastroenterology Report.2023;[Epub] CrossRef

5,999 View
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Lung and Thoracic cancer

Predictive Value of Interstitial Lung Abnormalities for Postoperative Pulmonary Complications in Elderly Patients with Early-stage Lung Cancer: Won Gi Jeong, Yun-Hyeon Kim, Jong Eun Lee, In-Jae Oh, Sang Yun Song, Kum Ju Chae, Hye Mi Park; Cancer Res Treat. 2022;54(3):744-752. Published online September 28, 2021; DOI: https://doi.org/10.4143/crt.2021.772

Abstract PDF Supplementary Material PubReader ePub

Purpose
Identifying pretreatment interstitial lung abnormalities (ILAs) is important because of their predictive value for complications after lung cancer treatment. This study aimed to assess the predictive value of ILAs for postoperative pulmonary complications (PPCs) in elderly patients undergoing curative resection for early-stage non-small cell lung cancer (NSCLC).
Materials and Methods
Elderly patients (age ≥ 70 years) who underwent curative resection for pathologic stage I or II NSCLC with normal preoperative spirometry results (pre-bronchodilator forced expiratory volume in 1 s to forced vital capacity [FVC] ratio > 0.70 and FVC ≥ 80% of the predicted value) between January 2012 and December 2019 were retrospectively identified. Univariable and multivariable regression analyses were performed to assess risk factors for PPCs. The Kaplan–Meier method and log-rank test were used to analyze the relationship between ILAs and postoperative mortality. One-way analysis of variance was performed to assess the correlation between ILAs and hospital stay duration.
Results
A total of 262 patients (median age, 73 [interquartile range, 71–76] years; 132 male) were evaluated. A multivariable logistic regression model revealed that, among several relevant risk factors, fibrotic ILAs independently predicted both overall PPCs (adjusted odds ratio [OR], 4.84; 95% confidence interval [CI], 1.35–17.38; p=0.016) and major PPCs (adjusted OR, 8.72; 95% CI, 1.71–44.38; p=0.009). Fibrotic ILAs were significantly associated with higher postoperative mortality and longer hospital stay (F=5.21, p=0.006).
Conclusion
Pretreatment fibrotic ILAs are associated with PPCs, higher postoperative mortality, and longer hospital stay.

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Prevalence and prognostic significance of interstitial lung abnormalities in lung cancer: A meta-analysis
Ruiyuan Yang, Haoyu Wang, Dan Liu, Weimin Li
Lung Cancer.2025; : 108458. CrossRef
Pretreatment Interstitial Lung Abnormalities Detected on Abdominal Computed Tomography Scans in Prostate Cancer Patients
Hyun Jin Kim, Won Gi Jeong, Jeong Yeop Lee, Hyo-Jae Lee, Byung Chan Lee, Hyo Soon Lim, Yun-Hyeon Kim
Journal of Computer Assisted Tomography.2024; 48(3): 406. CrossRef
Interstitial Lung Abnormalities
Noriaki Wada, Gary M. Hunninghake, Hiroto Hatabu
Clinics in Chest Medicine.2024; 45(2): 433. CrossRef
Incidence and risk factors of pulmonary complications after lung cancer surgery: A systematic review and meta-analysis
Ting Deng, Jiamei Song, Jinmei Tuo, Yu Wang, Jin Li, Lorna Kwai Ping Suen, Yan Liang, Junliang Ma, Shaolin Chen
Heliyon.2024; 10(12): e32821. CrossRef
Survival impact of fibrotic interstitial lung abnormalities in resected stage IA non-small cell lung cancer
Won Gi Jeong, Yun-Hyeon Kim
The British Journal of Radiology.2023;[Epub] CrossRef
Radiologic Progression of Interstitial Lung Abnormalities following Surgical Resection in Patients with Lung Cancer
Yoon Joo Shin, Jeong Geun Yi, Mi Young Kim, Donghee Son, Su Yeon Ahn
Journal of Clinical Medicine.2023; 12(21): 6858. CrossRef
Mycophenolate mofetil versus cyclophosphamide plus in patients with connective tissue disease-associated interstitial lung disease: Efficacy and safety analysis
Pengfei Wang, Li Zhang, Qian Guo, Lifen Zhao, Yanyan Hao
Open Medicine.2023;[Epub] CrossRef
Clinical implication of interstitial lung abnormality in elderly patients with early‐stage non‐small cell lung cancer
Seong Woo Cho, Won Gi Jeong, Jong Eun Lee, In‐Jae Oh, Sang Yun Song, Hye Mi Park, Hyo‐Jae Lee, Yun‐Hyeon Kim
Thoracic Cancer.2022; 13(7): 977. CrossRef

7,083 View
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Gastrointestinal cancer

Inhibition of WEE1 Potentiates Sensitivity to PARP Inhibitor in Biliary Tract Cancer: Hye-Rim Seo, Ah-Rong Nam, Ju-Hee Bang, Kyoung-Seok Oh, Jae-Min Kim, Jeesun Yoon, Tae-Yong Kim, Do-Youn Oh; Cancer Res Treat. 2022;54(2):541-553. Published online August 6, 2021; DOI: https://doi.org/10.4143/crt.2021.473

Abstract PDF PubReader ePub

Purpose
Up to 20% of patients with biliary tract cancer (BTC) have alterations in DNA damage response (DDR) genes, including homologous recombination (HR) genes. Therefore, the DDR pathway could be a promising target for new drug development in BTC. We aim to investigate the anti-tumor effects using poly(ADP-ribose) polymerase (PARP) and WEE1 inhibitors in BTC.
Materials and Methods
We used 10 BTC cell lines to evaluate an anti-tumor effect of olaparib (a PARP inhibitor) and AZD1775 (a WEE1 inhibitor) in in vitro. Additionally, we established SNU869 xenograft model for in vivo experiments.
Results
In this study, we observed a modest anti-proliferative effect of olaparib. DNA double-strand break (DSB) and apoptosis were increased by olaparib in BTC cells. However, olaparib-induced DNA DSB was repaired through the HR pathway, and G2 arrest was induced to secure the time for repair. As AZD1775 typically regulates the G2/M checkpoint, we combined olaparib with AZD1775 to abrogate G2 arrest. We observed that AZD1775 downregulated p-CDK1, a G2/M cell cycle checkpoint protein, and induced early mitotic entry. AZD1775 also decreased CtIP and RAD51 expression and disrupted HR repair. In xenograft model, olaparib plus AZD1775 treatment reduced tumor growth more potently than did monotherapy with either drug.
Conclusion
This is the first study to suggest that olaparib combined with AZD1775 can induce synergistic anti-tumor effects against BTC. Combination therapy that blocks dual PARP and WEE1 has the potential to be further clinically developed for BTC patients.

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Current and Future Therapeutic Targets for Directed Molecular Therapies in Cholangiocarcinoma
Philipp Heumann, Andreas Albert, Karsten Gülow, Denis Tümen, Martina Müller, Arne Kandulski
Cancers.2024; 16(9): 1690. CrossRef
Combined strategies with PARP inhibitors for the treatment of BRCA wide type cancer
Yijun Xie, Di Xiao, Duo Li, Mei Peng, Wei Peng, Huaxin Duan, Xiaoping Yang
Frontiers in Oncology.2024;[Epub] CrossRef
Update on Combination Strategies of PARP Inhibitors
Zhuoqun Lin, Lingfang Wang, Ziyu Xing, Fenfen Wang, Xiaodong Cheng
Cancer Control.2024;[Epub] CrossRef
The mechanism and clinical application of DNA damage repair inhibitors combined with immune checkpoint inhibitors in the treatment of urologic cancer
Deqian Xie, Bowen Jiang, Shijin Wang, Qifei Wang, Guangzhen Wu
Frontiers in Cell and Developmental Biology.2023;[Epub] CrossRef
DNA Damage Response Inhibitors in Cholangiocarcinoma: Current Progress and Perspectives
Öykü Gönül Geyik, Giulia Anichini, Engin Ulukaya, Fabio Marra, Chiara Raggi
Cells.2022; 11(9): 1463. CrossRef
Targeted Therapy of HPV Positive and Negative Tonsillar Squamous Cell Carcinoma Cell Lines Reveals Synergy between CDK4/6, PI3K and Sometimes FGFR Inhibitors, but Rarely between PARP and WEE1 Inhibitors
Ourania N. Kostopoulou, Mark Zupancic, Mariona Pont, Emma Papin, Monika Lukoseviciute, Borja Agirre Mikelarena, Stefan Holzhauser, Tina Dalianis
Viruses.2022; 14(7): 1372. CrossRef
Targeted Therapy with PI3K, PARP, and WEE1 Inhibitors and Radiotherapy in HPV Positive and Negative Tonsillar Squamous Cell Carcinoma Cell Lines Reveals Synergy while Effects with APR-246 Are Limited
Karin Byskata, Monika Lukoseviciute, Filippo Tuti, Mark Zupancic, Ourania N. Kostopoulou, Stefan Holzhauser, Tina Dalianis
Cancers.2022; 15(1): 93. CrossRef

7,325 View
232 Download
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7 Crossref

Hematologic malignancy

Predictive Factors of Event-Free Survival at 24 Months in Patients with Peripheral T-Cell Lymphoma: A Retrospective Study: Yu Ri Kim, Soo-Jeong Kim, Hye Sun Lee, Soyoung Jeon, Hyunsoo Cho, Haerim Chung, Ji Eun Jang, June-Won Cheong, Yoo Hong Min, Jin Seok Kim; Cancer Res Treat. 2022;54(2):613-620. Published online August 5, 2021; DOI: https://doi.org/10.4143/crt.2021.270

Abstract PDF PubReader ePub

Purpose
Event-free survival at 24 months (EFS24) is known to be a surrogate marker for overall survival (OS) for patients with peripheral T-cell lymphoma (PTCL). We examined the role of EFS24 in PTCL compared to diffuse large B-cell lymphoma (DLBCL), and then assessed the clinical predictive factors of achieving EFS24.
Materials and Methods
Patients with newly diagnosed PTCL treated with anthracycline-based chemotherapy were included. Subsequent OS was defined as the time elapsed from 24 months after diagnosis until death from any cause in those who achieved EFS24.
Results
Overall, 153 patients were evaluated, and 51 patients (33.3%) achieved EFS24. Patients who achieved EFS24 showed superior OS compared to patients who did not (p < 0.001). EFS24 could stratify the subsequent OS although it did not reach to that of the general population. After matching the PTCL group to the DLBCL group based on the international prognostic index, the subsequent OS in patients who achieved EFS24 was similar between the two groups (p=0.094). Advanced stage was a significant factor to predict the failing EFS24 by multivariable analysis (p < 0.001).
Conclusion
Patients with PTCL who achieve EFS24 could have a favorable subsequent OS. Since advanced disease stage is a predictor of EFS24 failure, future efforts should focus on developing novel therapeutic strategies for PTCL patients presenting with advanced disease.

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Clinical significance and predictive risk factors for event-free survival at 24 months in patients with PTCL, NOS
Zheng Cao, Xiaojun Wang, Xuemin Xue, Xiaoli Feng
Annals of Hematology.2024; 103(3): 869. CrossRef
Validity of event-free survival as a surrogate endpoint in haematological malignancy: Review of the literature and health technology assessments
Sarit Assouline, Adriana Wiesinger, Clare Spooner, Jelena Jovanović, Max Schlueter
Critical Reviews in Oncology/Hematology.2022; 175: 103711. CrossRef

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Breast cancer

Effect of Postoperative Radiotherapy after Primary Tumor Resection in De Novo Stage IV Breast Cancer: A Multicenter Retrospective Study (KROG 19-02): Yeon Joo Kim, Yeon-Joo Kim, Yong Bae Kim, Ik Jae Lee, Jeanny Kwon, Kyubo Kim, Jihye Cha, Myungsoo Kim, In Young Jo, Jung Hoon Kim, Jaehyeon Park, Jin Hee Kim, Juree Kim, Kyung Hwan Shin, Su Ssan Kim; Cancer Res Treat. 2022;54(2):478-487. Published online July 12, 2021; DOI: https://doi.org/10.4143/crt.2021.632

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to investigate the impact of postoperative radiotherapy (PORT) in de novo metastatic breast cancer (dnMBC) patients undergoing planned primary tumor resection (PTR) and to identify the subgroup of patients who would most benefit from PORT.
Materials and Methods
This study enrolled 426 patients with dnMBC administered PTR alone or with PORT. The primary and secondary outcomes were overall and progression-free survival (OS and PFS), respectively.
Results
The median follow-up time was 53.7 months (range, 3.1 to 194.4). The 5-year OS and PFS rates were 73.2% and 32.0%, respectively. For OS, clinical T3/4 category, triple-negative breast cancer (TNBC), postoperative chemotherapy alone were significantly poor prognostic factors, and administration of PORT failed to show its significance. Regarding PFS, PORT was a favorable prognostic factor (hazard ratio, 0.64; 95% confidence interval, 0.50 to 0.82; p < 0.001), in addition to T1/2 category, ≤ 5 metastases, and non-TNBC. According to the multivariate analyses of OS in the PORT group, we divided the patients into three groups (group 1, T1/2 and non-TNBC [n=193]; group 2, T3/4 and non-TNBC [n=171]; and group 3, TNBC [n=49]), and evaluated the effect of PORT. Although PORT had no significance for OS in all subgroups, it was a significant factor for good prognosis regarding PFS in groups 1 and 2, not in group 3.
Conclusion
PORT was associated with a significantly better PFS in patients with dnMBC who underwent PTR. Patients with clinical T1/2 category and non-TNBC benefited most from PORT, while those with TNBC showed little benefit.

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Letter to the editor for the article“Tumor margin irregularity degree is an important preoperative predictor of adverse pathology for clinical T1/2 renal cell carcinoma and the construction of predictive model”
Yaping Miao, Lexin Wang, Ping Chen, Jiaan Lu, Guanhu Yang, Hao Chi
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The prognostic differences and the effect of postmastectomy radiotherapy between post‐chemotherapy ypT1‐2ypN1 and de novo pT1‐2N1 breast cancer
Tian Yang, Xiaorong Zhong, Jun Wang, Zhongzheng Xiang, Yuanyuan Zeng, Siting Yu, Zelei Dai, Ningyue Xu, Ting Luo, Lei Liu
Cancer Medicine.2023; 12(7): 8112. CrossRef
Impact of high dose radiotherapy for breast tumor in locoregionally uncontrolled stage IV breast cancer: a need for a risk-stratified approach
Nalee Kim, Haeyoung Kim, Won Park, Won Kyung Cho, Tae Gyu Kim, Young-Hyuck Im, Jin Seok Ahn, Yeon Hee Park, Ji-Yeon Kim
Radiation Oncology.2023;[Epub] CrossRef
Machine learning predicts the prognosis of breast cancer patients with initial bone metastases
Chaofan Li, Mengjie Liu, Jia Li, Weiwei Wang, Cong Feng, Yifan Cai, Fei Wu, Xixi Zhao, Chong Du, Yinbin Zhang, Yusheng Wang, Shuqun Zhang, Jingkun Qu
Frontiers in Public Health.2022;[Epub] CrossRef
Factors Influencing Prognosis in Patients with De Novo Stage IV Breast Cancer: A Systematic Review and Meta-Analysis
Meilin Zhang, Zining Jin, Yingying Xu, Bo Chen, Jian Song, Muyao Li, Feng Jin, Ang Zheng
SSRN Electronic Journal .2022;[Epub] CrossRef

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Gastrointestinal cancer

Real-World Efficacy Data and Predictive Clinical Parameters for Treatment Outcomes in Advanced Esophageal Squamous Cell Carcinoma Treated with Immune Checkpoint Inhibitors: Jwa Hoon Kim, Bokyung Ahn, Seung-Mo Hong, Hwoon-Yong Jung, Do Hoon Kim, Kee Don Choi, Ji Yong Ahn, Jeong Hoon Lee, Hee Kyoung Na, Jong Hoon Kim, Yong-Hee Kim, Hyeong Ryul Kim, Hyun Joo Lee, Sung-Bae Kim, Sook Ryun Park; Cancer Res Treat. 2022;54(2):505-516. Published online June 23, 2021; DOI: https://doi.org/10.4143/crt.2020.1198

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to evaluate the real-world efficacy of immune checkpoint inhibitors (ICIs), and to identify clinicolaboratory factors to predict treatment outcomes in patients with advanced esophageal squamous cell carcinoma (ESCC) receiving ICIs.
Materials and Methods
Sixty patients with metastatic or unresectable ESCC treated with nivolumab (n=48) or pembrolizumab (n=12) as ≥ second-line treatment between 2016 and 2019 at Asan Medical Center were included.
Results
The median age of the patients was 68 years (range, 52 to 76 years), and 93.3% were male. Most patients had metastatic disease (81.7%) and had been previously treated with fluoropyrimidines, platinum, and taxane. In 53 patients with measurable disease, the overall response rate and disease control rate were 15.1% and 35.8%, respectively. With a median follow-up duration of 16.0 months, the median progression-free survival (PFS) and overall survival (OS) were 1.9 months (95% confidence interval [CI], 1.54 to 2.19) and 6.4 months (95% CI, 4.77 to 8.11), respectively. After multivariate analysis, recent use of antibiotics, low prognostic nutrition index (< 35.93), high Glasgow Prognosis Score (≥ 1) at baseline, and ≥ 1.4-fold increase in neutrophil-to-lymphocyte ratio after one cycle from baseline were significantly unfavorable factors for both PFS and OS. Younger age (< 65 years) was a significant factor for unfavorable PFS and hyponatremia (< 135 mmol/L) for unfavorable OS.
Conclusion
The use of ICIs after the failure of chemotherapy showed comparable efficacy in patients with advanced ESCC in real practice; this may be associated with host immune-nutritional status, which could be predicted by clinical and routine laboratory factors.

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豊木村
The Japanese Journal of SURGICAL METABOLISM and NUTRITION.2023; 57(6): 183. CrossRef
Prognostic and predictive impact of neutrophil‐to‐lymphocyte ratio and HLA‐I genotyping in advanced esophageal squamous cell carcinoma patients receiving immune checkpoint inhibitor monotherapy
Lin Wang, Yanrong Zhu, Bo Zhang, Xi Wang, Hongnan Mo, Yuchen Jiao, Jiachen Xu, Jing Huang
Thoracic Cancer.2022; 13(11): 1631. CrossRef
Prognostic Nutritional Index Predicts Response and Prognosis in Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis
Liwei Ni, Jing Huang, Jiyuan Ding, Junyan Kou, Tingting Shao, Jun Li, Liujie Gao, Wanzhen Zheng, Zhen Wu
Frontiers in Nutrition.2022;[Epub] CrossRef
The impact of antibiotic use on clinical features and survival outcomes of cancer patients treated with immune checkpoint inhibitors
Jiaxin Zhou, Guowei Huang, Wan-Ching Wong, Da-hai Hu, Jie-wen Zhu, Ruiman Li, Hong Zhou
Frontiers in Immunology.2022;[Epub] CrossRef
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Pengfei Li, Yutian Lai, Long Tian, Qinghua Zhou
Cancer Medicine.2022; 11(16): 3048. CrossRef
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Won Suk Lee, Dong Sung Kim, Jeong Hun Kim, Yoonki Heo, Hannah Yang, Eun-Jin Go, Jin Hyoung Kim, Seung Joon Lee, Byung Cheol Ahn, Jung Sun Yum, Hong Jae Chon, Chan Kim
Journal for ImmunoTherapy of Cancer.2022; 10(6): e004799. CrossRef
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Yusheng Guo, Dongqiao Xiang, Jiayu Wan, Lian Yang, Chuansheng Zheng
Cancers.2022; 14(21): 5297. CrossRef
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Deniz Can Guven, Taha Koray Sahin, Enes Erul, Alessandro Rizzo, Angela Dalia Ricci, Sercan Aksoy, Suayib Yalcin
Frontiers in Molecular Biosciences.2022;[Epub] CrossRef
Nomogram Based on Monocyte-to-Lymphocyte Ratio to Predict Survival of Unresectable Esophageal Squamous Cell Carcinoma Who Receive First-Line PD-1/PD-L1 Inhibitors Combined with Chemotherapy
Xiaolu Ma, Yongfeng Ding, Jiong Qian, Mingyu Wan, Ning Li, Chenyu Mao, Cheng Xiao, Haiping Jiang, Yulong Zheng, Luntao Wu, Xiaoyu Chen, Nong Xu
Current Oncology.2022; 29(11): 8937. CrossRef

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Pediatric cancer

Vincristine, Irinotecan, and Temozolomide as a Salvage Regimen for Relapsed or Refractory Sarcoma in Children and Young Adults: Hee Young Ju, Meerim Park, Jun Ah Lee, Hyeon Jin Park, Seog Yun Park, June Hyuk Kim, Hyun Guy Kang, Hee Chul Yang, Byung-Kiu Park; Cancer Res Treat. 2022;54(2):563-571. Published online June 14, 2021; DOI: https://doi.org/10.4143/crt.2021.178

Abstract PDF PubReader ePub

Purpose
No standard salvage regimen is available for relapsed or refractory sarcoma. We investigated the efficacy and toxicity of the vincristine, irinotecan, and temozolomide combination (VIT) for relapsed or refractory sarcomas of variable histology in children and young adults.
Materials and Methods
We retrospectively reviewed data from the relapsed or refractory sarcoma patients who were treated with VIT. The VIT protocol was given every 3 weeks as follows: vincristine, 1.5 mg/m² intravenously on day 1, irinotecan, 50 mg/m²/day intravenously on days 1-5, and temozolomide, 100 mg/m²/day orally on days 1-5.
Results
A total of 26 patients (12 males) with various sarcoma histology were included in the study. Most common diagnosis was rhabdomyosarcoma (n=8) followed by osteosarcoma (n=7). Median age at the start of VIT was 18.5 years (range, 2.0 to 39.9). VIT was delivered as 2nd to 7th line of treatment, with 4th line most common (9/26, 34.6%). Median number of VIT courses given was 3 (range, 1 to 18). Of the 25 evaluable patients, there was two partial response (PR) and 11 stable disease (SD) with an overall control rate (complete remission+PR+SD) of 52%. PR was seen in one (50%) of the two evaluable patients with Ewing sarcoma and one (14.3%) of the seven patients with osteosarcoma. Overall survival and progression-free survival rates were 79.3% and 33.9% at 1 year, and 45.5% and 25.4% at 2 years, respectively. There was no treatment-related mortality.
Conclusion
The VIT regimen was effective and relatively safe in our cohort of sarcoma patients.

Citations

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MGMT protein expression is a reliable predictive biomarker for temozolomide‐containing chemotherapy in osteosarcoma
Yoshinori Uchihara, Katsutsugu Umeda, Yosuke Yamada, Hiroaki Ito, Keiji Tasaka, Kiyotaka Isobe, Ryo Akazawa, Naoko Kawabata, Satoshi Saida, Itaru Kato, Hidefumi Hiramatsu, Takashi Noguchi, Akio Sakamoto, Yoshiki Arakawa, Ayumu Arakawa, Nobuyuki Yamamoto,
Cancer Science.2024; 115(10): 3394. CrossRef
Anlotinib combined with radiotherapy and chemotherapy for recurrent pelvic osteosarcoma treatment: a case report and literature review
Qian Chen, Kai Zheng, Ming Xu, Ning Yan, Gong Hai, Xiuchun Yu
Frontiers in Oncology.2023;[Epub] CrossRef
Irinotecan/temozolomide/vincristine

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International Journal of Molecular Sciences.2021; 22(22): 12299. CrossRef

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Head and Neck cancer

Long-term Survivals, Toxicities and the Role of Chemotherapy in Early-Stage Nasopharyngeal Carcinoma Patients Treated with Intensity-Modulated Radiation Therapy: A Retrospective Study with 15-Year Follow-up: Lin Wang, Jingjing Miao, Huageng Huang, Boyu Chen, Xiao Xiao, Manyi Zhu, Yingshan Liang, Weiwei Xiao, Shaomin Huang, Yinglin Peng, Xiaowu Deng, Xing Lv, Weixiong Xia, Yanqun Xiang, Xiang Guo, Fei Han, Chong Zhao; Cancer Res Treat. 2022;54(1):118-129. Published online June 7, 2021; DOI: https://doi.org/10.4143/crt.2021.101

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study was aimed to investigate long-term survivals and toxicities of early-stage nasopharyngeal carcinoma (NPC) in endemic area, evaluating the role of chemotherapy in stage II patients.
Materials and Methods
Totally 187 patients with newly diagnosed NPC and restaged American Joint Committee on Cancer/ International Union Against Cancer 8th T1-2N0-1M0 were retrospectively recruited. All received intensity-modulated radiotherapy (IMRT)±chemotherapy (CT) from 2001 to 2010.
Results
With 15.7-year median follow-up, 10-year locoregional recurrence-free survival, distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were 93.3%, 93.5%, 92.9% and 88.2%, respectively. Multivariable analyses showed cervical lymph nodes positive and pre-treatment prognostic nutritional index ≥ 52.0 could independently predict DMFS (p=0.036 and p=0.011), DSS (p=0.014 and p=0.026), and OS (p=0.002 and p < 0.001); Charlson comorbidity index < 3 points could predict DSS (p=0.011); age > 45 years (p=0.002) and pre-treatment lactate dehydrogenase ≥ 240 U/L (p < 0.001) predicted OS. No grade 4 late toxicity happened; grade 3 late toxicities included subcutaneous fibrosis (4.3%), deafness or otitis (4.8%), skin dystrophy (2.1%), and xerostomia (1.1%). No differences on survivals were shown between IMRT+CT vs. IMRT alone in stage II patients, even in T2N1M0 (p > 0.05). Unsurprising, patients in IMRT+CT had more acute gastrointestinal reaction, myelosuppression, mucositis, late ear toxicity, and cranial nerve injury (all p < 0.05) than IMRT alone group.
Conclusion
Superior tumor control and satisfying long-term outcomes could be achieved with IMRT in early-stage NPC with mild late toxicities. As CT would bring more toxicities, it should be carefully performed to stage II patients.

Citations

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Genistein and chlorin E6-loaded versatile nanoformulation for remodeling the hypoxia-related tumor microenvironment and boosting photodynamic therapy in nasopharyngeal carcinoma treatment
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Helena Levyn, Fan Yang, Nancy Y. Lee
Current Opinion in Otolaryngology & Head & Neck Surgery.2024; 32(1): 5. CrossRef
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Victor C. W. Tam, Jerry C. F. Ching, Sindy S. T. Yip, Virginia H. Y. Kwong, Catherine P. L. Chan, Kenneth C. W. Wong, Shara W. Y. Lee
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Jingjing Miao, Boyu Chen, Yunyun Xiao, Runda Huang, Xiao Xiao, Shunzhen Lu, Lu Zhang, Xuguang Wang, Ying Ouyang, Xiangfu Chen, Qiuyan Chen, Yanqun Xiang, Xiang Guo, Xiaowu Deng, Lin Wang, Haiqiang Mai, Chong Zhao
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Peter K. M. Ku, Alexander C. Vlantis, Rita W. M. Wong, Thomas S. C. Hui, Thomas Law, Louisa K. Y. Ng, Eddy W. Y. Wong, W. T. Chang, David R. Johnson, Florence S. T. Mok, K. H. Wong, Victor Abdullah, Andrew van Hasselt, Kathy Y. S. Lee, Michael C. F. Tong
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