Cancer Research and Treatment

Original Articles

Lung and Thoracic cancer

Histological Assessment and Interobserver Agreement in Major Pathologic Response for Non–Small Cell Lung Cancer with Neoadjuvant Therapy: Sungjin Kim, Jeonghyo Lee, Jin-Haeng Chung; Cancer Res Treat. 2025;57(2):401-411. Published online September 9, 2024; DOI: https://doi.org/10.4143/crt.2024.670

Abstract PDF Supplementary Material PubReader ePub: Purpose
Major pathologic response (MPR), defined as ≤ 10% of residual viable tumor (VT), is a prognostic factor in non–small cell lung cancer (NSCLC) after neoadjuvant therapy. This study evaluated interobserver reproducibility in assessing MPR, compared area-weighted and unweighted VT (%) calculation, and determined optimal VT (%) cutoffs across histologic subtypes for survival prediction.
Materials and Methods
This retrospective study included 108 patients with NSCLC who underwent surgical resection after neoadjuvant chemotherapy or chemoradiation at Seoul National University Bundang Hospital between 2009-2018. Three observers with varying expertise independently assessed tumor bed and VT (%) based on digital whole-slide images.
Results
Reproducibility in tumor bed delineation was reduced in squamous cell carcinoma (SqCC) with smaller tumor bed, although overall concordance was high (Dice coefficient, 0.96; intersection-over-union score, 0.92). Excellent agreement was achieved for VT (%) (intraclass correlation coefficient=0.959) and MPR using 10% cutoff (Fleiss’ kappa=0.911). Shifting between area-weighted and unweighted VT (%) showed only one case differing in MPR status out of 81 cases. The optimal cutoff was 10% for both adenocarcinoma (ADC) and SqCC. MPR+ was observed in 18 patients (17%), with SqCC showing higher MPR+ rates (p=0.044), lower VT (%) (p < 0.001), and better event-free survival (p=0.015) than ADC. MPR+ significantly improved overall survival (p=0.023), event-free survival (p=0.001), and lung cancer-specific survival (p=0.012).
Conclusion
While MPR assessment demonstrated robust reproducibility with minimal impact from the tumor bed, attention is warranted when evaluating smaller tumor beds in SqCC. A 10% cutoff reliably predicted survival across histologic subtypes with higher interobserver reproducibility.

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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.

Citations

Citations to this article as recorded by

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
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Lung Cancer.2024; 196: 107959. CrossRef
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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

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Gastrointestinal cancer

Prediction of Pathologic Response to Neoadjuvant Chemoradiotherapy in Patients with Esophageal Squamous Cell Carcinoma Incorporating Hematological Biomarkers: Yingjia Wu, Jinbin Chen, Lei Zhao, Qiaoqiao Li, Jinhan Zhu, Hong Yang, Suping Guo, Mian Xi; Cancer Res Treat. 2021;53(1):172-183. Published online September 4, 2020; DOI: https://doi.org/10.4143/crt.2020.594

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to develop a nomogram for predicting pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC) by integrating hematological biomarkers and clinicopathological characteristics.
Materials and Methods
Between 2003 and 2017, 306 ESCC patients who underwent neoadjuvant CRT followed by esophagectomy were analyzed. Besides clinicopathological factors, hematological parameters before, during, and after CRT were collected. Univariate and multivariate logistic regression analyses were performed to identify predictive factors for pCR. A nomogram model was built and internally validated.
Results
Absolute lymphocyte count (ALC), lymphocyte to monocyte ratio, albumin, hemoglobin, white blood cell, neutrophil, and platelet count generally declined, whereas neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) increased significantly following neoadjuvant CRT. After surgery, 124 patients (40.5%) achieved a pCR. The pCR group demonstrated significantly more favorable survival than the non-pCR group. On multivariate analysis, significant factors associated with pCR included sex, chemotherapy regimen, post-CRT endoscopic finding, pre-CRT NLR, ALC nadir during CRT, and post-CRT PLR, which were incorporated into the prediction model. The nomogram indicated good accuracy in predicting pCR, with a C-index of 0.75 (95% confidence interval, 0.71 to 0.78).
Conclusion
Female, chemotherapy regimen of cisplatin/vinorelbine, negative post-CRT endoscopic finding, pre-CRT NLR (≤ 2.1), ALC nadir during CRT (> 0.35 ×10⁹/L), and post-CRT PLR (≤ 83.0) were significantly associated with pCR in ESCC patients treated with neoadjuvant CRT. A nomogram incorporating hematological biomarkers to predict pCR was developed and internally validated, showing good predictive performance.

Citations

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Meng Zhang, Yukun Lu, Hongfu Sun, Chuanke Hou, Zichun Zhou, Xiao Liu, Qichao Zhou, Zhenjiang Li, Yong Yin
Translational Oncology.2024; 39: 101804. CrossRef
A machine learning approach using 18F-FDG PET and enhanced CT scan-based radiomics combined with clinical model to predict pathological complete response in ESCC patients after neoadjuvant chemoradiotherapy and anti-PD-1 inhibitors
Wei-Xiang Qi, Shuyan Li, Jifeng Xiao, Huan Li, Jiayi Chen, Shengguang Zhao
Frontiers in Immunology.2024;[Epub] CrossRef
Neoadjuvant PD-1 Plus Chemotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma
Ting Qian, Delin Liu, Guochun Cao, Zhipeng Chen, Qin Zhang
Technology in Cancer Research & Treatment.2024;[Epub] CrossRef
Nomogram for predicting pathologic complete response to neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma
Guihong Liu, Tao Chen, Xin Zhang, Binbin Hu, Jiayun Yu
Cancer Medicine.2024;[Epub] CrossRef
Pathological response to neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma in Eastern versus Western countries: meta-analysis
Xing Gao, Hidde C G Overtoom, Ben M Eyck, Shi-Han Huang, Daan Nieboer, Pieter C van der Sluis, Sjoerd M Lagarde, Bas P L Wijnhoven, Yin-Kai Chao, Jan J B van Lanschot
British Journal of Surgery.2024;[Epub] CrossRef
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Yunsong Liu, Zeliang Ma, Yongxing Bao, Xin Wang, Yu Men, Xujie Sun, Feng Ye, Kuo Men, Jianjun Qin, Nan Bi, Liyan Xue, Zhouguang Hui
Heliyon.2024; 10(13): e33702. CrossRef
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Chien-Ming Lo, Hung-I. Lu, Yu-Ming Wang, Yen-Hao Chen, Yu Chen, Li-Chun Chen, Shau-Hsuan Li
Perioperative Medicine.2024;[Epub] CrossRef
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Yalan Yang, Dao Xin, Huike Wang, Lulu Guan, Xiangrui Meng, Taiying Lu, Xiwen Bai, Feng Wang
Journal of Inflammation Research.2023; Volume 16: 1443. CrossRef
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Pathologic Observatiosn and P-glycoprotein Expression in Esophageal Carcinomas Treated with Preoperative chemotherapy: Chang Won Ha, Kyung Ja Cho, Young Mog Shim, Jae Ill Zo, Ja June Jang; J Korean Cancer Assoc. 1994;26(4):529-534.

Abstract PDF: Neoadjuvant chemotherpay of esophageal cancers is recently considered to be beneficial to downstaging of tumors. This study was aimed ta describe morphologic alterations and expression of P-glycoprotein in esophageal cancers after chemotherapy and discuse their clinical sig- nificances. Eleven cases of esophageal cancers which were surgicelly resected l-5 cycles of chemotherapy with C-DDP/VP-16/5-FU(PEF)or C-DDP/5-FU(FP) were reviewed. On microscopic examination, all of ll cases(100%) revealed no major pathologic alterations. Only five cases(45%) showed non-specific partial pathologic responses, histologically observing foreign body reaction, calcification, necrosis, desmoplasia, vascular dilatation, and nuclear anaplasia. The changes were also observed in metastatic tumors in regional lymph nodes. The presence of non-specific pathologic responses and downstaging of tumors did not correlate each other. Immunohistochemically, all of the cases were negative for P-glycoprotein. Our data suggest that PEF or FP neoadjuvant chemotherpay for esophageal cancers is ineffecitive.

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