Cancer Research and Treatment

Original Articles

Relationships between the Microbiome and Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer: Hye In Lee, Bum-Sup Jang, Ji Hyun Chang, Eunji Kim, Tae Hoon Lee, Jeong Hwan Park, Eui Kyu Chie; Received June 2, 2024 Accepted December 13, 2024 Published online December 16, 2024; DOI: https://doi.org/10.4143/crt.2024.521 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study aimed to investigate the dynamic changes in the microbiome of patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiotherapy (nCRT), focusing on the relationship between the microbiome and response to nCRT.
Materials and Methods
We conducted a longitudinal study involving 103 samples from 26 patients with LARC. Samples were collected from both the tumor and normal rectal tissues before and after nCRT. Diversity, taxonomic, and network analyses were performed to compare the microbiome profiles across different tissue types, pre- and post-nCRT time-points, and nCRT responses.
Results
Between the tumor and normal tissue samples, no differences in microbial diversity and composition were observed. However, when pre- and post-nCRT samples were compared, there was a significant decrease in diversity, along with notable changes in composition. Non-responders exhibited more extensive changes in their microbiome composition during nCRT, characterized by an increase in pathogenic microbes. Meanwhile, responders had relatively stable microbiome communities with more enriched butyrate-producing bacteria. Network analysis revealed distinct patterns of microbial interactions between responders and non-responders, where butyrate-producing bacteria formed strong networks in responders, while opportunistic pathogens formed strong networks in non-responders. A Bayesian network model for predicting the nCRT response was established, with butyrate-producing bacteria playing a major predictive role.
Conclusion
Our study demonstrated a significant association between the microbiome and nCRT response in LARC patients, leading to the development of a microbiome-based response-prediction model. These findings suggest potential applications of microbiome signatures for predicting and optimizing nCRT treatment in LARC patients.

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Hematologic malignancy

Higher Microbial Abundance and Diversity in Bronchus-Associated Lymphoid Tissue Lymphomas Than in Non-cancerous Lung Tissues: Jung Heon Kim, Jae Sik Kim, Noorie Choi, Jiwon Koh, Yoon Kyung Jeon, Ji Hyun Chang, Eung Soo Hwang, Il Han Kim; Cancer Res Treat. 2025;57(2):580-589. Published online September 30, 2024; DOI: https://doi.org/10.4143/crt.2024.689

Abstract PDF Supplementary Material PubReader ePub: Purpose
It is well known that the majority of the extranodal marginal zone lymphomas of mucosa-associated lymphoid tissues (MALT lymphomas) are associated with microbiota, e.g., gastric MALT lymphoma with Helicobacter pylori. In general, they are very sensitive to low-dose radiotherapy and chemotherapeutic agents. The microbiota profile is not clearly elucidated in bronchus-associated lymphoid tissue (BALT) lymphoma, a rare type of MALT lymphoma in the lung. Thus, this study aimed to clarify the intratumor microbiome in BALT lymphoma using the third-generation next-generation sequencing (NGS) method.
Materials and Methods
DNAs were extracted from 12 formalin-fixed paraffin-embedded (FFPE) tumor tissues obtained from BALT lymphoma patients diagnosed between 1990 and 2016. 16S rRNA gene was amplified by polymerase chain reaction. Amplicons were sequenced using a Nanopore platform. Next-generation sequencing analysis was performed to assess microbial profiles. For comparison, FFPE specimens from nine non-cancerous lung tissues were also analyzed.
Results
Specific bacterial families including Burkholderiaceae, Bacillaceae, and Microbacteriaceae were associated with BALT lymphoma by a linear discriminant analysis effect size approach. Although the number of specimens was limited, BALT lymphomas exhibited significantly higher microbial abundance and diversity with distinct microbial composition patterns and correlation networks than non-cancerous lung tissues.
Conclusion
This study provides the first insight into intratumor microbiome in BALT lymphoma using the third-generation NGS method. A distinct microbial composition suggests the presence of a unique tumor microenvironment of BALT lymphoma.

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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.

Citations

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Impact of postmastectomy radiotherapy on locoregional recurrence and survival in patients with ypN0 breast cancer after neoadjuvant chemotherapy: A comprehensive meta-analysis and systematic review
Fangjie Ding, Junfeng Zhao, Xue Wu, Xiaoman Liu, Yunxing Yang, Ying Li, Lili Qiao, Yingying Zhang
Journal of Cancer Research and Therapeutics.2025; 21(2): 477. CrossRef
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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Postmastectomy Radiation Therapy for Node-Negative Breast Cancer of 5 cm or Larger Tumors: A Multicenter Retrospective Analysis (KROG 20-03): Kyubo Kim, Jinhong Jung, Haeyoung Kim, Wonguen Jung, Kyung Hwan Shin, Ji Hyun Chang, Su Ssan Kim, Won Park, Jee Suk Chang, Yong Bae Kim, Sung Ja Ahn, Ik Jae Lee, Jong Hoon Lee, Hae Jin Park, Jihye Cha, Juree Kim, Jin Hwa Choi, Taeryool Koo, Jeanny Kwon, Jin Hee Kim, Mi Young Kim, Shin-Hyung Park, Yeon-Joo Kim; Cancer Res Treat. 2022;54(2):497-504. Published online August 25, 2021; DOI: https://doi.org/10.4143/crt.2021.933

Abstract PDF PubReader ePub

Purpose
To evaluate the role of postmastectomy radiation therapy (PMRT) in patients with node-negative breast cancer of 5cm or larger tumors undergoing mastectomy
Materials and Methods
Medical records of 274 patients from 18 institutions treated with mastectomy between January 2000 and December 2016 were retrospectively reviewed. Among these, 202 patients underwent PMRT, while 72 did not. Two hundred and forty-one patients (88.0%) received systemic chemotherapy, and 172 (62.8%) received hormonal therapy. Patients receiving PMRT were younger, more likely to have progesterone receptor-positive tumors, and received adjuvant chemotherapy more frequently compared with those without PMRT (p <0.001, 0.018, and <0.001, respectively). Other characteristics were not significantly different between the two groups.
Results
With a median follow-up of 95 months (range, 1-249), there were 9 locoregional recurrences, and 20 distant metastases. The 8-year locoregional recurrence-free survival rates were 98.0% with PMRT and 91.3% without PMRT (p=0.133), and the 8-year disease-free survival (DFS) rates were 91.8% with PMRT and 73.9% without PMRT (p=0.008). On multivariate analysis incorporating age, histologic grade, lymphovascular invasion, hormonal therapy, chemotherapy, and PMRT, the absence of lymphovascular invasion and the receipt of PMRT were associated with improved DFS (p=0.025 and 0.009, respectively).
Conclusion
Locoregional recurrence rate was very low in node-negative breast cancer of 5cm or larger tumors treated with mastectomy regardless of the receipt of PMRT. However, PMRT was significantly associated with improved DFS. Further investigation is needed to confirm these findings.

Citations

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Outcomes with and without postmastectomy radiotherapy for pT3N0‐1M0 breast cancer: An institutional experience
Xinxin Rao, Xuanyi Wang, Kairui Jin, Yilan Yang, Xu Zhao, Zhe Pan, Weiluo Lv, Zhen Zhang, Li Zhang, Xiaoli Yu, Xiaomao Guo
Cancer Medicine.2024;[Epub] CrossRef
The effect of radiotherapy on patients with pathological stage IIB breast cancer after breast-conserving surgery or mastectomy: A cohort study
Yi-Ying Pan, Tzu-Yu Lai, Cheng-Ying Shiau, Ling-Ming Tseng, I-Chun Lai, Yu-Ming Liu, Pin-I Huang
Journal of the Chinese Medical Association.2024; 87(2): 202. CrossRef
Post-mastectomy radiation therapy after breast reconstruction: from historic dogmas to practical expert agreements based on a large literature review of surgical and radiation therapy considerations
Yazid Belkacemi, Meena S. Moran, Burcu Celet Ozden, Yazan Masannat, Fady Geara, Mohamed Albashir, Nhu Hanh To, Kamel Debbi, Mahmoud El Tamer
Critical Reviews in Oncology/Hematology.2024; 200: 104421. CrossRef
Impact of the 21-gene recurrence score testing on chemotherapy selection and clinical outcomes in T3N0 luminal breast cancer
Ke Liu, Jia-Yi Li, Guan-Qiao Li, Zhen-Yu He, San-Gang Wu
Expert Review of Anticancer Therapy.2024; 24(12): 1283. CrossRef
Post-Mastectomy Radiation Therapy: Applications and Advancements
Jessica L. Thompson, Steven G. Allen, Cecilia Pesavento, Corey W. Speers, Jacqueline S. Jeruss
Current Breast Cancer Reports.2022; 14(3): 75. CrossRef

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BCL2 Regulation according to Molecular Subtype of Breast Cancer by Analysis of The Cancer Genome Atlas Database: Ki-Tae Hwang, Kwangsoo Kim, Ji Hyun Chang, Sohee Oh, Young A Kim, Jong Yoon Lee, Se Hee Jung, In Sil Choi; Cancer Res Treat. 2018;50(3):658-669. Published online July 4, 2017; DOI: https://doi.org/10.4143/crt.2017.134

Abstract PDF Supplementary Material PubReader ePub

Purpose
We investigated B-cell lymphoma 2 (BCL2) regulation across DNA, RNA, protein, and methylation status according to molecular subtype of breast cancer using The Cancer Genome Atlas (TCGA) database.
Materials and Methods
We analyzed clinical and biological data on 1,096 breast cancers from the TCGA database. Biological data included reverse phase protein array (RPPA), mRNA sequencing (mRNA-seq), mRNA microarray, methylation, copy number alteration linear, copy number alteration nonlinear, and mutation data.
Results
The luminal A and luminal B subtypes showed upregulated expression of RPPA and mRNAseq and hypomethylation compared to the human epidermal growth factor receptor 2 (HER2) and triple-negative subtypes (all p < 0.001). No mutations were found in any subjects. High mRNA-seq and high RPPA were strongly associated with positive estrogen receptor, positive progesterone receptor (all p < 0.001), and negative HER2 (p < 0.001 and p=0.002, respectively). Correlation analysis revealed a strong positive correlation between protein and mRNA levels and a strong negative correlation between methylation and protein and mRNA levels (all p < 0.001). The high BCL2 group showed superior overall survival compared to the low BCL2 group (p=0.006).
Conclusion
The regulation of BCL2 was mainly associated with methylation across the molecular subtypes of breast cancer, and luminal A and luminal B subtypes showed upregulated expression of BCL2 protein, mRNA, and hypomethylation. Although copy number alteration may have played a minor role, mutation status was not related to BCL2 regulation. Upregulation of BCL2 was associated with superior prognosis than downregulation of BCL2.

Citations

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AL16ALA-SOD2 polymorphism predicts recurrence risk of breast cancer in patients treated with adjuvant tamoxifen
Maiquidieli Dal Berto, Laura Martin Manfroi, Aniúsca Vieira dos Santos, Giovana Tavares dos Santos, Gabriela Krüger da Costa, Camila Macedo Boaro, Péttala Rigon, Rafael José Vargas Alves, Claudia Giuliano Bica
Advances in Cancer Biology - Metastasis.2023; 8: 100108. CrossRef
Clinicopathological features and prognosis of patients with HER2-low breast cancer
Xin Yang, Yao Li, Xu lu, Xiaotian Ren, Bin Hua
BMC Cancer.2023;[Epub] CrossRef
Development of a prediction model for radiotherapy response among patients with head and neck squamous cell carcinoma based on the tumor immune microenvironment and hypoxia signature
Guang‐Li Zhu, Kai‐Bin Yang, Cheng Xu, Rui‐Jia Feng, Wen‐Fei Li, Jun Ma
Cancer Medicine.2022; 11(23): 4673. CrossRef
Significance of Bcl-2 expression in breast cancer
Nitika Kumari, Natarajan Suresh, Josephine A.
Biomedicine.2022; 42(4): 775. CrossRef
Detecting the expression of HRs and BCL2 via IHC can help identify luminal A-like subtypes of triple-positive breast cancers
Yingying Xu, Yonghao Liang, Guanghao Yin
Clinical and Translational Oncology.2022; 25(4): 1024. CrossRef
Early stability and late random tumor progression of a HER2-positive primary breast cancer patient-derived xenograft
Lorena Landuzzi, Arianna Palladini, Claudio Ceccarelli, Sofia Asioli, Giordano Nicoletti, Veronica Giusti, Francesca Ruzzi, Marianna L. Ianzano, Laura Scalambra, Roberta Laranga, Tania Balboni, Maddalena Arigoni, Martina Olivero, Raffaele A. Calogero, Car
Scientific Reports.2021;[Epub] CrossRef
Prognostic influences of BCL1 and BCL2 expression on disease-free survival in breast cancer
Ki-Tae Hwang, Young A. Kim, Jongjin Kim, Hyeon Jeong Oh, Jeong Hwan Park, In Sil Choi, Jin Hyun Park, Sohee Oh, Ajung Chu, Jong Yoon Lee, Kyu Ri Hwang
Scientific Reports.2021;[Epub] CrossRef
p53 and BLC2 Immunohistochemical Expression Across Molecular Subtypes in 1099 Early Breast Cancer Patients With Long-Term Follow-up: An Observational Study
Alessandra Fabi, Marcella Mottolese, Anna Di Benedetto, Francesca Sperati, Cristiana Ercolani, Simonetta Buglioni, Cecilia Nisticò, Gianluigi Ferretti, Patrizia Vici, Letizia Perracchio, Paola Malaguti, Michelangelo Russillo, Claudio Botti, Edoardo Pescar
Clinical Breast Cancer.2020; 20(6): e761. CrossRef
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Young Ju Jeong, Hoon Kyu Oh, Hye Ryeon Choi, Sung Hwan Park
Diagnostics.2020; 10(11): 939. CrossRef
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Rafael Nacif-Pimenta, Alessandra da Silva Orfanó, Ilana A. Mosley, Shannon E. Karinshak, Kenji Ishida, Victoria H. Mann, Paulo Marcos Zech Coelho, José M. Correia da Costa, Michael H. Hsieh, Paul J. Brindley, Gabriel Rinaldi
Scientific Reports.2019;[Epub] CrossRef
A CTC-Cluster-Specific Signature Derived from OMICS Analysis of Patient-Derived Xenograft Tumors Predicts Outcomes in Basal-Like Breast Cancer
Hariprasad Thangavel, Carmine De Angelis, Suhas Vasaikar, Raksha Bhat, Mohit Kumar Jolly, Chandandeep Nagi, Chad J. Creighton, Fengju Chen, Lacey E. Dobrolecki, Jason T. George, Tanya Kumar, Noor Mazin Abdulkareem, Sufeng Mao, Agostina Nardone, Mothaffar
Journal of Clinical Medicine.2019; 8(11): 1772. CrossRef
BCL2L12: a multiply spliced gene with independent prognostic significance in breast cancer
Athina Kladi-Skandali, Diamantis C. Sideris, Andreas Scorilas
Clinical Chemistry and Laboratory Medicine (CCLM).2018; 57(2): 276. CrossRef

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Survey of the Patterns of Using Stereotactic Ablative Radiotherapy for Early-Stage Non-small Cell Lung Cancer in Korea: Sanghyuk Song, Ji Hyun Chang, Hak Jae Kim, Yeon Sil Kim, Jin Hee Kim, Yong Chan Ahn, Jae-Sung Kim, Si Yeol Song, Sung Ho Moon, Moon June Cho, Seon Min Youn; Cancer Res Treat. 2017;49(3):688-694. Published online October 31, 2016; DOI: https://doi.org/10.4143/crt.2016.219

Abstract PDF Supplementary Material PubReader ePub

Purpose
Stereotactic ablative radiotherapy (SABR) is an effective emerging technique for early-stage non-small cell lung cancer (NSCLC). We investigated the current practice of SABR for early-stage NSCLC in Korea.
Materials and Methods
We conducted a nationwide survey of SABR for NSCLC by sending e-mails to all board-certified members of the Korean Society for Radiation Oncology. The survey included 23 questions focusing on the technical aspects of SABR and 18 questions seeking the participants’ opinions on specific clinical scenarios in the use of SABR for early-stage NSCLC. Overall, 79 radiation oncologists at 61/85 specialist hospitals in Korea (71.8%) responded to the survey.
Results
SABR was used at 33 institutions (54%) to treat NSCLC. Regarding technical aspects, the most common planning methods were the rotational intensity-modulated technique (59%) and the static intensity-modulated technique (49%). Respiratory motion was managed by gating (54%) or abdominal compression (51%), and 86% of the planning scans were obtained using 4-dimensional computed tomography. In the clinical scenarios, the most commonly chosen fractionation schedule for peripherally located T1 NSCLC was 60 Gy in four fractions. For centrally located tumors and T2 NSCLC, the oncologists tended to avoid SABR for radiotherapy, and extended the fractionation schedule.
Conclusion
The results of our survey indicated that SABR is increasingly being used to treat NSCLC in Korea. However, there were wide variations in the technical protocols and fractionation schedules of SABR for early-stage NSCLC among institutions. Standardization of SABR is necessary before implementing nationwide, multicenter, randomized studies.

Citations

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Guidelines for safe practice of stereotactic body (ablative) radiation therapy: RANZCR 2023 update
Howard Yu‐hao Liu, Nicholas Hardcastle, Michael Bailey, Shankar Siva, Anna Seeley, Tamara Barry, Jeremy Booth, Louis Lao, Michelle Roach, Stacey Buxton, David Thwaites, Matthew Foote
Journal of Medical Imaging and Radiation Oncology.2024; 68(2): 217. CrossRef
Technical Giants But Biologic Infants: Defining a More Sophisticated Role for Local Therapy in Metastatic Disease
Sophia C. Kamran, David Palma, Matthew S. Katz, Anthony L. Zietman
Seminars in Radiation Oncology.2021; 31(3): 200. CrossRef
MiR-223-3p regulates cell viability, migration, invasion, and apoptosis of non-small cell lung cancer cells by targeting RHOB
Shufang Li, Yuping Feng, Yuxia Huang, Yu Liu, Yanxi Wang, Yan Liang, Hui Zeng, Hong Qu, Ling Wei
Open Life Sciences.2020; 15(1): 389. CrossRef

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Radiation-Induced Sarcoma: A 15-Year Experience in a Single Large Tertiary Referral Center: Kyung Su Kim, Ji Hyun Chang, Noorie Choi, Han-Soo Kim, Ilkyu Han, Kyung Chul Moon, Il Han Kim, Hak Jae Kim; Cancer Res Treat. 2016;48(2):650-657. Published online September 9, 2015; DOI: https://doi.org/10.4143/crt.2015.171

Abstract PDF PubReader ePub

Purpose
The purpose of this study is to report on the incidence and the experience in management of radiation-induced sarcoma (RIS) at a large single center in Korea for 15 years.
Materials and Methods
We retrospectively reviewed the sarcoma registry of a large institution from January 2000 to April 2014.
Results
Out of the 3,674 patients listed in the registry, 33 patients (0.9%) diagnosed with RIS were identified. The median latency of RIS was 12.1 years. The number of cases of RIS increased from four cases in the years 2000-2003 to 14 cases in the years 2012-2014. The most common histology was osteosarcoma (36.4%). The median follow-up period was 23.1 months, the median overall survival (OS) of all patients was 2.9 years, and their 5-year survival rate was 44.7%. Univariate and multivariate analyses showed association of the age at diagnosis (p=0.01) and the treatment aim (p=0.001) with the OS. The median OS and the 5-year survival rate of patients treated with curative surgery (n=19) were 9.6 years and 65%, respectively, and of the conservatively treated patients, 0.7 years and 0% (n=14). Re-irradiation was delivered to nine patients, and radiation toxicity was observed in five patients.
Conclusion
In this study, RIS accounted for 0.9% of the cases of sarcoma, with increasing incidence. Despite the association of curative resection with increased survival, it could be applied to only 58% of the patients. Considering the limited treatment options for RIS, conduct of a genetic study to identify the underlying mechanism of RIS is needed.

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