Hepatic focal nodular hyperplasia (FNH)–like lesions mimicking metastasis have been reported as rare complications of cytotoxic chemotherapy, but they have not previously been described in association with CDK4/6 inhibitors alone. We present the case of a 32-year-old chemotherapy-naïve woman with de novo hormone receptor (HR)–positive/HER2-negative metastatic breast cancer who was treated with first-line ribociclib and letrozole. After four cycles, imaging revealed a complete response of her bone metastases alongside a newly developed 5.5-cm hepatic lesion suspicious for visceral progression. Liver function tests remained normal. Two ultrasound-guided percutaneous core biopsies, performed three months apart and directly targeting the lesion, confirmed a benign FNH-like lesion without evidence of malignancy. Ribociclib was continued without modification; at last follow-up the patient remained in sustained complete oncologic response, with the hepatic lesion stable in size and no biochemical or clinical evidence of hepatic dysfunction. To our knowledge, this appears to be the first reported case of an FNH-like hepatic lesion temporally associated with ribociclib in a patient who had not received prior cytotoxic chemotherapy. The principal clinical message is that newly detected hepatic lesions arising during otherwise effective targeted therapy do not necessarily reflect disease progression, and that, in radiologically discordant cases, histopathologic confirmation may be required to avoid premature discontinuation or switching of effective treatment.
Joon Young Hur, Hana Kim, Soon Il Lee, Se Jun Park, Jina Yun, Seok Yun Kang, Cheolsik Kim, Seung-Hoon Beom, Hyeyeong Kim, So-Yeon Jeon, Jaemin Jo, Yongho Noh, Jong Gwang Kim, Hyun Jin Bang
Received February 14, 2026 Accepted May 27, 2026 Published online May 29, 2026
Purpose
The benefit of adjuvant chemotherapy (CTx) for high-risk stage II microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) colon cancer remains controversial with discordant international guidelines. This study evaluated outcomes comparing adjuvant chemotherapy group versus surgery only group.
Materials and Methods
This multicenter retrospective analysis included 192 patients with high-risk stage II MSI-H/dMMR colon cancer who underwent curative resection between 2010 and 2020. High-risk features included pT4, grade 3-4, lymphovascular invasion, bowel obstruction/perforation, perineural invasion (PNI), inadequate lymph node sampling (<12), or close margins. The primary endpoint was 5-year relapse-free survival (RFS), excluding second primary malignancies to isolate antitumor efficacy.
Results
Of 192 patients, 128 (66.7%) received adjuvant CTx and 64 (33.3%) underwent observation (median follow-up 60.5 months). Five-year RFS (94.0% vs. 83.7%; p=0.001) and OS (98.3% vs. 89.0%; p=0.001) were significantly higher with adjuvant CTx. Multivariate analysis confirmed adjuvant CTx as an independent predictor for RFS (HR 0.249, 95% CI 0.109-0.571; p=0.001) and OS (HR 0.155, 95% CI 0.051-0.470; p=0.001). PNI was also identified as a significant independent predictor of RFS (HR, 3.581; 95% CI, 1.529 to 8.387; p=0.003) and OS (HR, 4.968; 95% CI, 1.654 to 14.930; p=0.004). CTx-related toxicities were clinically manageable, and no treatment-related deaths were reported.
Conclusion
Adjuvant CTx significantly improves RFS and OS in high-risk stage II MSI-H/dMMR colon cancer, particularly in pT4 and PNI patients. These findings provide evidence to bridge NCCN and ESMO guideline discrepancies, supporting risk-stratified adjuvant CTx in this population.
Purpose Metastatic breast cancer (MBC) with severe hepatic dysfunction due to liver crisis presents a significant treatment challenge, as conventional chemotherapy often requires dose modifications, leading to reduced efficacy. The combination of platinum, 5-fluorouracil, and folinate (PFL) offers a rational treatment strategy. This study evaluates the efficacy and safety of PFL in MBC patients with liver crisis and explores predictive markers for treatment response.
Materials and Methods This retrospective cohort study, conducted at Taipei Veterans General Hospital, Taiwan, included 44 MBC patients with bilirubin ≥ 3 mg/dL treated between January 2015 and June 2024. Outcomes included bilirubin response rate (≥ 50% reduction from baseline), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events. The area under the curve analysis was used to determine the optimal cutoff for liver function assessment models, and Cox regression identified independent prognostic factors.
Results Among the 44 patients, 47.7% achieved a bilirubin response within a median of 19 days. Overall, the median PFS and OS were 1.4 and 1.9 months, respectively, but improved to 4.6 and 7.8 months in those achieving bilirubin response. The objective response rate was 22.7%, and the disease control rate was 29.5%. A fibrosis-4 (FIB-4) score < 9.1 predicted a 65% bilirubin response rate, while FIB-4 > 9.1 was also an independent predictor of OS. Grade 3 adverse events occurred in 36.4% of patients.
Conclusion The PFL regimen is effective in MBC patients with severe liver crisis with hyperbilirubinemia. A FIB-4 score < 9.1 may serve as a potential prognostic factor for bilirubin response and is associated with improved survival outcomes.
Purpose
Fibroblast growth factor receptor 2b (FGFR2b) is a promising therapeutic target in gastric cancer; however, its clinical relevance in immune checkpoint inhibitor (ICI)-based chemotherapy remains unclear. Therefore, this study aims to evaluate the expression pattern and predictive value of FGFR2b in patients undergoing first-line nivolumab plus chemotherapy.
Materials and Methods
This single-center study included 503 patients diagnosed with gastric cancer. Among them, 296 underwent nivolumab-chemotherapy, while 207 underwent chemotherapy alone. FGFR2b expression was assessed via immunohistochemistry using samples collected after mid-2022. FGFR2b positivity was defined as membranous staining intensity of 2+/3+ in ≥ 1% of tumor cells, with ≥ 10% as overexpression, and 1–9% as low expression.
Results
FGFR2b overexpression and positivity were identified in 9.3% and 16.7% of cases, respectively. Discordance between paired biopsy and surgical samples was observed (20.0% and 40.0% for overexpression and positivity, respectively), indicating marked intratumoral heterogeneity. Among patients who underwent nivolumab-chemotherapy, FGFR2b overexpression and low expression were associated with favorable survival trends compared to those of FGFR2b-negative cases. These associations were not observed in patients treated with chemotherapy alone. Compared to chemotherapy alone, nivolumab-chemotherapy was associated with a greater survival benefit in patients with FGFR2b positivity. Multivariate interaction analyses revealed a significant interaction between FGFR2b expression and nivolumab-based chemotherapy.
Conclusion
FGFR2b expression exhibits substantial intratumoral heterogeneity in gastric cancer and may be linked to favorable outcomes in patients undergoing first-line ICI plus chemotherapy. Therefore, future studies should validate this finding, along with mechanistic investigations.
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Patient-derived organoids in gastric cancer: bridging the tumor microenvironment to functional precision oncology Ji Ma, Xinyang Liu, Hongtao Xu, Chuan Jiang Frontiers in Bioengineering and Biotechnology.2026;[Epub] CrossRef
Dong Hyun Kim, Sanyeowool An, Hongyul Ahn, Han Song, Ka-Won Kang, Sang Eun Yoon, Seok Jin Kim, Hyo Jung Kim, Youngil Koh, Deok-Hwan Yang, Consortium for Improving Survival of Lymphoma (CISL)
Received September 6, 2025 Accepted November 11, 2025 Published online November 12, 2025
Purpose Relapsed or refractory (R/R) primary central nervous system lymphoma (PCNSL) is an aggressive malignancy for which salvage chemotherapy has limited efficacy. We conducted an investigator-initiated, single-arm, multicenter phase II trial to evaluate the efficacy and safety of a chemotherapy-free salvage regimen comprising rituximab, lenalidomide, and poseltinib (R2P) in patients with R/R PCNSL.
Materials and Methods The R2P regimen consisted of two phases: six cycles of induction with rituximab, lenalidomide, and poseltinib, followed by three cycles of consolidation with lenalidomide and poseltinib. The primary endpoints were complete response rate (CRR) and overall response rate (ORR). Secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS).
Results A total of 10 patients were enrolled (one withdrew before cycle 1; nine were evaluable for efficacy). The median age was 70 years (range, 53 to 75 years), and all had received methotrexate-based first-line chemotherapy. The ORR was 55.6%, and the CRR was 33.3%. The median PFS was 5.6 months, and the median OS was not reached. Next-generation sequencing was performed in four patients (three responders and one non-responder). CD79B missense mutations were identified in all three responders. A total of 11 adverse events (AEs) were observed in six patients. The most common AE was neutropenia (30.0%). The only grade ≥ 3 AE was a single case of grade 3 neutropenia. No dose modifications were required due to toxicity.
Conclusion Poseltinib in combination with lenalidomide and rituximab showed activity in patients with R/R PCNSL, warranting further investigation in larger studies.
Purpose Relapsed and refractory acute myeloid leukemia (R/R AML) has a poor prognosis due to chemotherapy resistance. Mitochondrial dysfunction contributes to this resistance, but the role of the RNA component of mitochondrial RNA processing endoribonuclease (RMRP) in R/R AML remains unclear.
Materials and Methods Mass spectrometry identified molecules linked to chemoresistance in AML. The role of RMRP was examined by assessing its impact on mitochondrial transfer in the AML bone marrow microenvironment. Transmission electron microscopy and western blotting were used to study mitochondrial function and autophagy in RMRP-knockdown AML cells.
Results RMRP was overexpressed in R/R AML, and its silencing sensitized AML cells to chemotherapy drugs. RMRP knockdown reduced mitochondrial respiratory capacity, mitochondrial DNA copy numbers, and mitochondrial gene transcription. It also led to altered mitophagy markers and increased mitochondrial DNA methylation. Immunoprecipitation revealed RMRP–telomerase reverse transcriptase complex formation, suggesting a role in post-transcriptional regulation of mitochondrial function and reactive oxygen species production.
Conclusion High RMRP expression in R/R AML is linked to mitochondrial dysfunction and chemotherapy resistance, providing new insights into potential therapeutic strategies to overcome drug resistance in this disease.
Yoon-Koo Kang, Min-Hee Ryu, Do-Youn Oh, Sang Cheul Oh, Sun Young Rha, Keun-Wook Lee, Ik Joo Chung, Sung Yong Oh, Sun Jin Sym, Won Ki Kang, Jong Gwang Kim, Byoung Yong Shim, In-Ho Kim, Jin Young Kim, Eun-Kee Song, Hyo-Jin Lee, Seok Yun Kang, Dong-Hoe Koo, So Yeon Oh
Cancer Res Treat. 2026;58(3):846-859. Published online July 2, 2025
Purpose
We report the safety and efficacy of nivolumab+chemotherapy for first-line treatment of advanced or recurrent gastric or gastroesophageal junction cancer in the Korean subpopulation of the ATTRACTION-4 clinical trial.
Materials and Methods
ATTRACTION-4 (NCT02746796) was a double-blind, randomized, placebo-controlled clinical trial of patients aged ≥ 20 years with histologically confirmed unresectable advanced or recurrent gastric or gastroesophageal junction cancer. Patients received nivolumab or placebo, both combined with physician-choice chemotherapy (oxaliplatin plus oral S-1 [tegafur–gimeracil–oteracil] [SOX] or oral capecitabine [CAPOX]).
Results
Overall, 464 patients were initially screened in Korea and 291 were randomized to nivolumab+chemotherapy (total/SOX/CAPOX: 148/66/82 patients) or placebo+chemotherapy (total/SOX/CAPOX: 143/61/82 patients). Centrally assessed progression-free survival (median, 14.75 vs. 8.34 months; hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.39 to 0.73; p < 0.001), overall survival (19.7 vs. 14.9 months; HR, 0.78; 95% CI, 0.60 to 1.02; p=0.065), overall response rate (54.7% vs. 47.6%), and duration of response (16.03 vs. 9.86 months) favored nivolumab+chemotherapy vs. placebo+chemotherapy. Grade ≥ 3 treatment-related adverse events (TRAEs) (56.1% vs. 44.1%), and any-grade endocrine (9.5% vs. 4.2%), hepatic (23.0% vs. 14.7%), hypersensitivity and infusion reactions (15.5% vs. 7.0%), renal (4.1% vs. 0.7%), and skin (44.6% vs. 23.1%) TRAEs tended to be more frequent in the nivolumab+chemotherapy group.
Conclusion
These findings demonstrate the clinical benefit of nivolumab combined with chemotherapy (either SOX or CAPOX) for first-line treatment of gastric cancer/gastroesophageal junction cancer in Korean patients.
Skin toxicity induced by chemotherapy or molecular targeted therapy combined with immune checkpoint inhibitors in Asian patients: A literature review by the Japanese Pharmacist-led Oncodermatology Study Team Yohei Iimura, Junichi Higuchi, Akimitsu Maeda, Kazuhiro Shimomura, Hirotoshi Iihara, Hironori Fujii, Takuya Iwamoto, Yoshitaka Saito, Hisanaga Nomura, Keiko Komori, Hidenori Tokuda, Ryuta Urakawa, Tatsuya Sumiya, Ryosuke Yanai, Mariko Kono, Masaki Ihira, International Journal of Clinical Oncology.2026; 31(6): 957. CrossRef
Overcoming diagnostic pitfalls in primary gastric squamous cell carcinoma: the imperative of adequate sampling in an elderly female patient, case report Wanhui Dong, Li Cheng, Jing Xu, Sheng Xu, Yuling Yin, Qingming Sun, Yong Wu, Yuling Leng Frontiers in Oncology.2025;[Epub] CrossRef
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Purpose
This study aimed to evaluate the impact of postoperative adjuvant chemotherapy (AC) on survival outcomes in breast cancer (BC) patients who have already undergone neoadjuvant chemotherapy (NAC) followed by surgery.
Materials and Methods
Data from a population-based cohort (2010-2020) were analyzed for BC patients treated with NAC and surgery. Univariate and multivariate Cox regression identified prognostic factors for overall survival (OS), and a nomogram was developed and validated. Personalized scores from the nomogram were used for risk stratification to assess the effect of postoperative AC.
Results
A total of 15,921 BC patients were analyzed, with 11,144 in the training cohort and 4,777 in the validation cohort. The key prognostic indicators for OS included age, race, marital status, histological grade, BC subtype, T category, N category, type of surgery, and response to NAC (all p < 0.05). The nomogram effectively predicted individualized OS rates and stratified patients into various risk categories. Postoperative AC was found to significantly enhance OS in the high-risk subgroup (p=0.011 in the training cohort, p=0.012 in the overall population). However, for the low-risk subgroup, there was no significant survival benefit from postoperative AC (p=0.130 for the training cohort, p=0.588 for the overall population), suggesting that some patients might safely forgo unnecessary postoperative AC.
Conclusion
This study efficiently differentiates between varying levels of risk, enabling clinicians to identify patients unlikely to benefit from postoperative AC and thus reduce the likelihood of overtreatment.
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Purpose This study aimed to investigate the impact of physical activity on dementia risk among cancer survivors in South Korea.
Materials and Methods This retrospective, population-based cohort study included 344,152 cancer survivors identified from the National Health Insurance Service database in South Korea. The mean follow-up time was 5.81 years. Different levels of physical activity post-cancer diagnosis, ranging from inactive to highly active, were assessed. The primary outcome was the incidence of overall dementia, Alzheimer’s disease, and vascular dementia. Secondary outcomes included dementia risk stratified by cancer type and treatment (chemotherapy and radiation).
Results Of the total participants, 24,363 (7.08%) developed dementia. The risk of overall dementia decreased sequentially across the exercise groups compared to the inactive group: insufficiently active (adjusted hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.86 to 0.92), active (adjusted HR, 0.85; 95% CI, 0.83 to 0.88), and highly active (adjusted HR, 0.79; 95% CI, 0.76 to 0.82). This inverse relationship between exercise and dementia risk was statistically significant across various cancer types and was consistent regardless of age, comorbidities, and whether or not excluding the first 1, 2 years.
Conclusion Among cancer survivors in South Korea, increased physical activity post-diagnosis was associated with a significantly lower risk of dementia. These findings underscore the importance of promoting physical activity in cancer survivors for cognitive health.
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Cancer Res Treat. 2026;58(1):61-70. Published online February 12, 2025
Purpose
Current guidelines recommend vaccination at least 2 weeks before chemotherapy initiation to optimize the immune response despite limited evidence. Our previous study indicated no differences in short-term immune response for the 13-valent pneumococcal conjugate vaccine (PCV13) according to the vaccination timing. This study aims to investigate the long-term efficacy of PCV13 and clinical factors associated with the respective antibody response.
Materials and Methods
Patients with gastric or colorectal cancer who received adjuvant chemotherapy were enrolled and divided into two groups: vaccinated 2 weeks before chemotherapy (arm A) and vaccinated concurrently with chemotherapy (arm B). Serum samples were collected before vaccination and in one month, 3 years, and 5 years. Immune responses were measured using enzyme-linked immunosorbent assay and multiplex opsonophagocytosis assay.
Results
Including 63 patients, both groups showed an initial increase in the geometric mean titers of opsonophagocytic activity and the geometric mean concentrations of serotype-specific IgG levels after one month, followed by a decline at 3 and 5 years, particularly for serotypes 1, 14, 18C, and 19A. Despite the decline, global protection was maintained for 5 years, although global response decreased. The two arms did not show significant differences in immunogenicity nor in factors such as vaccination timing, age, cancer type, or chemotherapy regimen.
Conclusion
Vaccination timing is not a significant factor for the immunogenicity of PCV13 in cancer patients undergoing adjuvant chemotherapy. Global protection against pneumococcal infection was sustained for > 5 years, and global response remained in over half of patients.
Although gastric cancer remains a significant global health burden, its treatment strategies vary across different geographical regions, leading to distinct guidelines. In Asia, particularly in Korea, D2 gastrectomy followed by adjuvant chemotherapy has been established as the standard treatment for stage II/III gastric cancer based on landmark clinical trials. However, this “one-size-fits-all” approach requires refinement as emerging evidence suggests heterogeneous outcomes even within the same stage. This review discusses the evolving landscape of adjuvant treatment in gastric cancer, emphasizing the transition towards precision medicine. Recent molecular characterization of gastric cancer has revealed distinct subtypes with varying prognoses and chemotherapy responses, exemplified by the favorable outcomes of microsatellite instability–high tumors without adjuvant chemotherapy. Additionally, clinical factors including sub-stages within stage II/III, patient performance status, comorbidities, and personal preferences should be considered in treatment decisions. The integration of these molecular and clinical factors, along with shared decision-making between physicians and patients, represents a crucial step toward personalized treatment approaches. Looking ahead, the field is poised for further evolution with the emergence of immune checkpoint inhibitors, growing evidence for neoadjuvant chemotherapy in selected cases, and the potential of circulating tumor DNA as a biomarker for minimal residual disease. This comprehensive approach to treatment decision-making, considering both tumor biology and patient factors, will be essential for realizing precision medicine in gastric cancer care.
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Purpose
This study aimed to assess prognostic values of the POST-Treatment Extent of tumor (POSTTEXT) system and clinical factors after neoadjuvant chemotherapy in hepatoblastoma patients and evaluate benefits of post-treatment imaging and clinical factors concomitant with Children’s Hepatic Tumors International Collaboration–Hepatoblastoma Stratification (CHIC-HS) system.
Materials and Methods
This single-center retrospective study of hepatoblastoma cases (2006-2022) included pediatric patients receiving ≥ 4 cycles of neoadjuvant chemotherapy, with pre- and post-treatment imaging and complete medical records. Clinical data included age, sex, and serum α-fetoprotein (AFP) levels. Cox regression analyses identified predictors of event-free survival (EFS). Time-dependent receiver operating characteristic curves assessed the predictive power of combining the CHIC-HS risk stratification with post-treatment factors. Inter-reader agreement was analyzed using weighted kappa.
Results
Among the 109 hepatoblastoma patients, 73 (mean age, 2.2±2.7 years) met the inclusion criteria. Prognostic factors for EFS included AFP levels after the fourth cycle of neoadjuvant chemotherapy (hazard ratio [HR], 1.233; 95% confidence interval [CI], 1.086 to 1.400; p=0.001), tumor size change ratio (HR, 0.654; 95% CI, 0.448 to 0.955; p=0.030), and POSTTEXT annotation factor M (HR, 5.209; 95% CI, 1.639 to 16.553; p=0.005). Incorporating AFP levels after the fourth cycle of neoadjuvant chemotherapy into the CHIC-HS improved predictive power (p=0.043). POSTTEXT system showed better inter-reader agreement than PRE-Treatment Extent of tumor (PRETEXT).
Conclusion
Predictors of EFS in hepatoblastoma include AFP levels after the fourth cycle of neoadjuvant chemotherapy, tumor size change ratio, and metastasis (POSTTEXT M). Combining AFP levels after the fourth cycle of neoadjuvant chemotherapy to the CHIC-HS improved the predictive ability.
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Purpose The role of neoadjuvant chemotherapy in locally advanced sinonasal squamous cell carcinoma (SNSCC) has not been established prospectively. We conducted a phase II trial of neoadjuvant chemotherapy (NAC) with docetaxel/cisplatin/5-fluorouracil (TPF) in this population.
Materials and Methods Eligible patients had unresectable, locally advanced SNSCC, defined as T3/4 category or potential compromise of critical organ function on surgery. Three TPF (docetaxel 75 mg/m2 and cisplatin 75 mg/m2 on day 1, 5-fluorouracil 1,000 mg/m2 on days 1-4 every 3 weeks) cycles were administered with prophylactic pegteograstim. The primary outcome was the objective response rate (ORR); the secondary outcomes included 2-year progression-free survival (PFS), eyeball preservation rate, and safety.
Results Among 28 patients screened, 25 were evaluable for efficacy (one screen-failure; two evaluable for safety only). The confirmed ORR was 72.0%. The definitive post-NAC treatment comprised chemoradiotherapy (n=15) and surgery (n=10). With a median follow-up of 25.5 months, median PFS was not reached and the 2-year PFS rate was 60.4%. Response to NAC was related to prolonged PFS (p=0.038). No patient underwent eyeball exenteration at the data cutoff point. Treatment-related adverse events of grade ≥ 3 were neutropenia (48.1%) including febrile neutropenia (14.8%), followed by acute kidney injury (22.2%), nausea/vomiting (11.1%), anemia (7.4%), thrombocytopenia (7.4%), and enterocolitis (3.7%).
Conclusion TPF NAC showed a promising efficacy and might help preserve critical structures in this population, which needs to be validated in a large prospective trial (KCT0003377).
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Purpose This cross-sectional study aimed to examine which chemotherapy (CTx) terms were most difficult to understand for cancer patients and identify vulnerable patient populations who might need extra support to understand the terms.
Materials and Methods We listed 56 CTx-related terms based on the experts’ review, then 300 cancer patients and their caregivers completed a questionnaire that assessed literacy in CTx terms (LCT), functional health literacy, and empowerment. Descriptive analysis was performed to examine which CTx-related terms were most difficult for them. Logistic regression analyses were performed to identify factors associated with LCT level.
Results Of the total 300 people, 162 (54.0%) were in the low-scoring group in LCT. Low-scoring group had a higher proportion of males, lower monthly income, and lived at the province, compared to the high scoring group. The participants tended to have difficulties in understanding terms related to blood count, risk of infection, and symptoms written in Sino-Korean. In the multivariable logistic regression, male participants (adjusted odds ratio [aOR], 2.59; 95% confidence interval [CI], 1.48 to 4.62), those with no cancer-related information-seeking (aOR, 4.32; 95% CI, 1.75 to 12.33), and those with low empowerment (aOR, 3.07; 95% CI, 1.83 to 5.23) were more likely to have a low level of LCT.
Conclusion There were still linguistic health literacy challenges faced by cancer patients and their caregivers, specifically in understanding chemotherapy-related terms. Minimizing medical jargon and Sino-Korean terms and empowering patients to be ready for treatment are necessary.
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Cancer Res Treat. 2025;57(3):770-780. Published online November 12, 2024
Purpose The nProfiler 1 Stomach Cancer Assay (nProfiler1), designed to predict responses to fluorouracil-based adjuvant chemotherapy, measures the expression of four gastric cancer target genes (GZMB, WARS, SFRP4, and CDX1). The randomized phase III POST trial aimed to compare the efficacies of two adjuvant S-1-based doublet chemotherapies: S-1 plus cisplatin (SP) and S-1 plus docetaxel (DS). This study aimed to validate the nProfiler1 assay using a distinct cohort from the POST trial.
Materials and Methods The nProfiler1 assay stratifies patients into three groups (low-risk, intermediate-risk, and high-risk) using the prognostic single-patient classifier and two groups (chemotherapy-benefit and no-benefit) using the predictive single-patient classifier. The nProfiler1 assay was applied to formalin-fixed paraffin-embedded slides obtained from the POST trial. Disease-free survival (DFS) and overall survival (OS), including 5-year survival rates, were calculated for the enrolled patients.
Results Of the 153 patients in the POST trial, 118 were included in the post-hoc analysis. With a median follow-up of 57.9 months, no significant difference in DFS or OS was observed between the SP and DS groups. The prognostic single-patient classifier predicted the OS in the SP group (p=0.043) but not in the DS group (p=0.594). The chemotherapy-benefit group exhibited numerically longer DFS than the no-benefit group in the SP and DS groups.
Conclusion The nProfiler1 assay offers valuable insights into the prognosis and efficacy of adjuvant chemotherapy based on fluorouracil plus platinum doublet regimens but not docetaxel-containing regimens. Further validation with larger patient cohorts and different regimens is warranted.
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Purpose Thyroid transcription factor 1 (TTF-1) expression is a useful predictor of treatment efficacy in advanced non-squamous non–small cell lung cancer (NSCLC). This study aimed to evaluate whether TTF-1 could predict the effectiveness of chemotherapy versus chemoimmunotherapy in patients with non-squamous NSCLC with programmed death ligand-1 (PD-L1) expression between 1% and 49%.
Materials and Methods We conducted a retrospective study of patients with NSCLC who were treated with chemotherapy or chemoimmunotherapy between March 2016 and May 2023. The patients had histologically confirmed NSCLC, stage III-IV or postoperative recurrence, TTF-1 measurements, and PD-L1 expression levels between 1% and 49%. Clinical data were analyzed to evaluate the effect of TTF-1 expression on treatment efficacy.
Results This study included 283 of 624 patients. TTF-1–positive patients showed longer progression-free survival (PFS) and overall survival (OS) (PFS: 6.4 months [95% confidence interval (CI), 5.0 to 9.4] vs. 4.1 months [95% CI, 2.7 to 6.1], p=0.03; OS: 17.9 months [95% CI, 15.2 to 28.1] vs. 9.4 months [95% CI, 6.3 to 17.0], p < 0.01) in the chemotherapy cohorts (n=93). In the chemoimmunotherapy cohort (n=190), there was no significant difference in PFS and OS between TTF-1–positive and –negative groups (PFS: 7.6 months [95% CI, 6.4 to 11.0] vs. 6.0 months [95% CI, 3.6 to 12.6], p=0.59; OS: 25.0 months [95% CI, 18.0 to 49.2] vs. 21.3 months [95% CI, 9.8 to 28.8], p=0.09).
Conclusion In patients with NSCLC with PD-L1 expression between 1% and 49%, TTF-1 expression was a predictor of chemotherapeutic, but not chemoimmunotherapeutic, efficacy.
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Impact of Thyroid Transcription Factor‐1 Expression on Outcomes of Platinum‐Based Chemoimmunotherapy in Advanced or Recurrent Non‐Squamous Non‐Small Cell Lung Cancer Ryohei Kamada, Hiroshi Yokouchi, Shohei Mizobuchi, Ken Kuwahara, Yasushi Mizukami, Hidenori Mizugaki, Noriyuki Yamada, Hajime Asahina, Hirofumi Adachi, Yoshihiro Matsuno, Satoshi Oizumi Thoracic Cancer.2026;[Epub] CrossRef
Predictive value of TTF-1 expression for stratifying outcomes between dual ICI and chemoimmunotherapy in patients with PD-L1-negative NSCLC Naoya Nishioka, Daiki Murata, Koichi Azuma, Kazuhiro Ito, Takashi Nomizo, Kazuhiko Yamada, Tatsuya Imabayashi, Kentaro Iwanaga, Kenji Chibana, Takayo Ota, Yuuya Nishii, Akira Nakao, Asuka Okada, Kosuke Hamai, Takenori Sakai, Taishi Harada, Keiko Tanimura, International Journal of Clinical Oncology.2026;[Epub] CrossRef
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The expression of PD-1 ligands in the immune microenvironment was altered in TTF-1-negative lung adenocarcinoma Hiroyuki Yamada, Hiromu Yano, Eri Matsubara, Shukang Zhao, Yusuke Shinchi, Cheng Pan, Takamasa Koga, Kosuke Fujino, Yukio Fujiwara, Koei Ikeda, Yoshihiro Komohara, Makoto Suzuki Human Cell.2025;[Epub] CrossRef
TTF‑1 expression is associated with survival in patients with non‑squamous non‑small cell lung cancer treated with immune checkpoint inhibitor therapy Nozomu Murayama, Minehiko Inomata, Daisuke Furukawa, Moe Hashizume, Naoki Takata, Zenta Seto, Kotaro Tokui, Seisuke Okazawa, Shingo Imanishi, Toshiro Miwa, Ryuji Hayashi, Kohji Takagi, Kenichi Hirabayashi Molecular and Clinical Oncology.2025; 24(2): 1. CrossRef
Tumor microenvironment is intrinsically hypoxic with abundant hypoxia-inducible factors-1α (HIF-1α), a primary regulator of the cellular response to hypoxia and various stresses imposed on the tumor cells. HIF-1α increases radioresistance and chemoresistance by reducing DNA damage, increasing repair of DNA damage, enhancing glycolysis that increases antioxidant capacity of tumors cells, and promoting angiogenesis. In addition, HIF-1α markedly enhances drug efflux, leading to multidrug resistance. Radiotherapy and certain chemotherapy drugs evoke profound anti-tumor immunity by inducing immunologic cell death that release tumor-associated antigens together with numerous pro-immunological factors, leading to priming of cytotoxic CD8+ T cells and enhancing the cytotoxicity of macrophages and natural killer cells. Radiotherapy and chemotherapy of tumors significantly increase HIF-1α activity in tumor cells. Unfortunately, HIF-1α effectively promotes various immune suppressive pathways including secretion of immune suppressive cytokines, activation of myeloid-derived suppressor cells, activation of regulatory T cells, inhibition of T cells priming and activity, and upregulation of immune checkpoints. Consequently, the anti-tumor immunity elevated by radiotherapy and chemotherapy is counterbalanced or masked by the potent immune suppression promoted by HIF-1α. Effective inhibition of HIF-1α may significantly increase the efficacy of radiotherapy and chemotherapy by increasing radiosensitivity and chemosensitivity of tumor cells and also by upregulating anti-tumor immunity.
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Cancer Res Treat. 2024;56(4):1084-1095. Published online April 30, 2024
Purpose Optimal treatment for stage IIIA/N2 non–small cell lung cancer (NSCLC) is controversial. We aimed to assess the efficacy and safety of adjuvant pembrolizumab for stage IIIA/N2 NSCLC completely resected after neoadjuvant concurrent chemoradiation therapy (CCRT).
Materials and Methods In this open-label, single-center, single-arm phase 2 trial, patients with stage IIIA/N2 NSCLC received adjuvant pembrolizumab for up to 2 years after complete resection following neoadjuvant CCRT. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and safety. As an exploratory biomarker analysis, we evaluated the proliferative response of blood CD39+PD-1+CD8+ T cells using fold changes in the percentage of proliferating Ki-67+ cells from days 1 to 7 of cycle 1 (Ki-67D7/D1).
Results Between October 2017 and October 2018, 37 patients were enrolled. Twelve (32%) and three (8%) patients harbored EGFR and ALK alterations, respectively. Of 34 patients with programmed cell death ligand 1 assessment, 21 (62%), nine (26%), and four (12%) had a tumor proportion score of < 1%, 1%-50%, and ≥ 50%, respectively. The median follow-up was 71 months. The median DFS was 22.4 months in the overall population, with a 5-year DFS rate of 29%. The OS rate was 86% at 2 years and 76% at 5 years. Patients with tumor recurrence within 6 months had a significantly lower Ki-67D7/D1 among CD39+PD-1+CD8+ T cells than those without (p=0.036). No new safety signals were identified.
Conclusion Adjuvant pembrolizumab may offer durable disease control in a subset of stage IIIA/N2 NSCLC patients after neoadjuvant CCRT and surgery.
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Cancer Res Treat. 2024;56(4):1136-1145. Published online April 29, 2024
Purpose Varlitinib is a pan-human epidermal growth factor receptor (HER) inhibitor targeting epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and HER4. We present a phase Ib/II study of a combination of varlitinib and weekly paclitaxel as a second-line treatment for patients with EGFR/HER2 co-expressing advanced gastric cancer (AGC).
Materials and Methods Patients whose tumors with EGFR and HER2 overexpression by immunohistochemistry (≥ 1+) were enrolled. Varlitinib and paclitaxel were investigated every 4 weeks. After determining the recommended phase II dose (RP2D) in phase Ib, a phase II study was conducted to evaluate the antitumor activity.
Results RP2D was treated with a combination of varlitinib (300 mg twice daily) and paclitaxel. Among 27 patients treated with RP2D, the median progression-free survival and overall survival (OS) were 3.3 months (95% confidence interval [CI], 1.7 to 4.9) and 7.9 months (95% CI, 5.0 to 10.8), respectively, with a median follow-up of 15.7 months. Among 16 patients with measurable disease, the objective response rate (ORR) and disease control rate were 31% and 88%, respectively. Patients with strong HER2 expression (n=8) had a higher ORR and longer OS, whereas those with strong EGFR expression (n=3) had poorer outcomes. The most common adverse events (AEs) of any grade were neutropenia (52%), diarrhea (27%), aspartate aminotransferase/alanine transaminase elevation (22%), and nausea (19%). No treatment-related deaths or unexpected AEs resulting from treatment cessation were observed in patients with RP2D.
Conclusion A combination of varlitinib and paclitaxel displayed manageable toxicity and modest antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy.
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Purpose This study aimed to investigate the efficacy and safety of using metronomic S-1 adjuvant chemotherapy in locoregionally advanced nasopharyngeal carcinoma (LANPC).
Materials and Methods We retrospectively collected data on patients diagnosed with LANPC between January 2016 and December 2021. All patients were treated with induction chemotherapy and concurrent chemoradiotherapy with or without metronomic chemotherapy (MC). Toxicities during MC were recorded. The chi-square test, Kaplan-Meier methods, propensity score matching (PSM), and Cox proportional hazards model were used for statistical analyses.
Results A total of 474 patients were identified, including 64 (13.5%) and 410 (83.5%) patients with or without receiving MC, respectively. Patients who received metronomic S-1 had significantly better 3-year locoregional recurrence-free survival (LRFS) (100% vs. 90.9%, p=0.038), distant metastasis-free survival (DMFS) (98.5% vs. 84.1%, p=0.002), disease-free survival (DFS) (98.4% vs. 77.5%, p < 0.001), and overall survival (OS) (98.0% vs. 87.7%, p=0.008) compared to those without metronomic S-1. The multivariate prognostic analysis revealed that metronomic S-1 was identified as an independent prognostic factor associated with better DMFS (hazard ratio [HR], 0.074; p=0.010), DFS (HR, 0.103; p=0.002) and OS (HR, 0.127; p=0.042), but not in LRFS (p=0.071). Similar results were found using PSM. Common adverse events observed in the metronomic S-1 group included leukopenia, neutropenia, increased total bilirubin, anorexia, rash/desquamation, and hyperpigmentation. All patients with adverse events were grade 1-2.
Conclusion It is worth conducting a randomized controlled trial to assess the effect of metronomic S-1 on survival outcomes and toxicities of LANPC.
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Purpose The aim of this retrospective study was to evaluate the efficacy of adjuvant cisplatin-based chemotherapy in patients with locally advanced upper tract urothelial carcinoma (UTUC), administered following radical nephroureterectomy.
Materials and Methods Patients with UTUC, arising from renal pelvis or ureter, staged pT3/T4 or N+ were treated with adjuvant chemotherapy following surgery. The chemotherapy consisted of gemcitabine 1,000 mg/m2 on days 1 and 8, cisplatin 70 mg/m2 on day 1. Treatment was repeated every 3 weeks for up to 4 cycles. Endpoints included disease-free survival (DFS), metastasis-free survival (MFS), and safety.
Results Among 89 eligible patients, 85 (95.5%) completed at least 3 cycles of adjuvant chemotherapy. Chemotherapy was well tolerated, the main toxicities being mild-to-moderate gastrointestinal toxic effects and pruritus. With a median follow-up of 37 months, median DFS was 30 months (95% confidence interval, 22 to 39), and the median MFS was not reached. The 3-year DFS and MFS were 44% and 56%, respectively. Multivariate analyses revealed that the main factor associated with DFS and MFS was the lymph node involvement, whereas age, T category, grade, or the primary site of UTUC were not significantly associated with DFS or MFS.
Conclusion Adjuvant cisplatin-based chemotherapy after radical surgery of pT3/T4 or N+ UTUC was feasible and may demonstrate benefits in DFS and MFS. Whether novel agents added to the chemotherapy regimen, as a concurrent combination or maintenance, impacts on survival or reduces the development of metastases remains to be studied.
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Purpose The locally advanced unresectable intrahepatic cholangiocarcinoma (ICC) has detrimental oncological outcomes. In this study, we aimed to investigate the efficacy of radiotherapy in patients with locally advanced unresectable ICC.
Materials and Methods Between 2001 and 2021, 116 patients were identified through medical record who underwent radiotherapy for locally advanced unresectable ICC. The resectability of ICC is determined by the multidisciplinary team at each institution. Overall survival (OS) were analyzed using the Kaplan-Meier method, and prognostic factors were analyzed using the Cox proportional hazards model.
Results The median equivalent radiotherapy dose in 2 Gy fractions (EQD2) was 52 Gy (range, 30 to 110 Gy). Forty-seven patients (40.5%) received sequential gemcitabine-cisplatin based chemotherapy (GEM-CIS CTx). Multivariate analysis identified two risk factors, EQD2 of ≥ 60 Gy and application of sequential GEM-CIS CTx for OS. Patients were grouped by these two risk factors: group 1, EQD2 ≥ 60 Gy with sequential GEM-CIS CTx (n=25); group 2, EQD2 < 60 Gy with sequential GEM-CIS CTx or fluoropyrimidine-based concurrent chemoradiotherapy (n=70); and group 3, radiotherapy alone (n=21). Curative resection was more frequently undergone in group 1 than in groups 2 or 3 (28% vs. 8.6% vs. 0%, respectively). Consequently, OS was significantly better in group 1 than in groups 2 and 3 (p < 0.05).
Conclusion Combined high-dose radiotherapy with sequential GEM-CIS CTx improved oncologic outcomes in patients with locally advanced unresectable ICC. Further prospective studies are required to validate these findings.
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Purpose The Korean Society of Pediatric Neuro-Oncology (KSPNO) conducted treatment strategies for children with medulloblastoma (MB) by using alkylating agents for maintenance chemotherapy or tandem high-dose chemotherapy (HDC) with autologous stem cell rescue (ASCR) according to the risk stratification. The purpose of the study was to assess treatment outcomes and complications based on risk-adapted treatment and HDC.
Materials and Methods Fifty-nine patients diagnosed with MB were enrolled in this study. Patients in the standard-risk (SR) group received radiotherapy (RT) after surgery and chemotherapy using the KSPNO M051 regimen. Patients in the high-risk (HR) group received two and four chemotherapy cycles according to the KSPNO S081 protocol before and after reduced RT for age following surgery and two cycles of tandem HDC with ASCR consolidation treatment.
Results In the SR group, 24 patients showed 5-year event-free survival (EFS) and overall survival (OS) estimates of 86.7% (95% confidence interval [CI], 73.6 to 100) and 95.8% (95% CI, 88.2 to 100), respectively. In the HR group, more infectious complications and mortality occurred during the second HDC than during the first. In the HR group, the 5-year EFS and OS estimates were 65.5% (95% CI, 51.4 to 83.4) and 72.3% (95% CI, 58.4 to 89.6), respectively.
Conclusion High intensity of alkylating agents for SR resulted in similar outcomes but with a high incidence of hematologic toxicity. Tandem HDC with ASCR for HR induced favorable EFS and OS estimates compared to those reported previously. However, infectious complications and treatment-related mortalities suggest that a reduced chemotherapy dose is necessary, especially for the second HDC.
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Purpose This study aimed to investigate the incidence and risk factors for secondary malignant neoplasms (SMN) in pediatric solid tumors, focusing on the effects of tandem high-dose chemotherapy (HDCT).
Materials and Methods Patients (aged < 19 years) diagnosed with or treated for pediatric solid tumors between 1994 and 2014 were retrospectively analyzed. The cumulative incidence of SMN was estimated using competing risk methods by considering death as a competing risk.
Results A total of 1,435 patients (413 with brain tumors and 1,022 with extracranial solid tumors) were enrolled. Seventy-one patients developed 74 SMNs, with a 10-year and 20-year cumulative incidence of 2.680±0.002% and 10.193±0.024%, respectively. The types of SMN included carcinoma in 28 (37.8%), sarcoma in 24 (32.4%), and hematologic malignancy in 15 (20.3%) cases. Osteosarcoma and thyroid carcinoma were the most frequently diagnosed tumors. Multivariate analysis showed that radiotherapy (RT) > 2, 340 cGy, and tandem HDCT were significant risk factors for SMN development. The SMN types varied according to the primary tumor type; carcinoma was the most frequent SMN in brain tumors and neuroblastoma, whereas hematologic malignancy and sarcomas developed more frequently in patients with sarcoma and retinoblastoma, respectively.
Conclusion The cumulative incidence of SMN in pediatric patients with solid tumors was considerably high, especially in patients who underwent tandem HDCT or in those who received RT > 2,340 cGy. Therefore, the treatment intensity should be optimized based on individual risk assessment and the long-term follow-up of pediatric cancer survivors.
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Purpose The female sex is reported to have a higher risk of adverse events (AEs) from cytotoxic chemotherapy. Few studies examined the sex differences in AEs and their impact on the use of medical services during adjuvant chemotherapy. This sub-study aimed to compare the incidence of any grade and grade ≥ 3 AEs, healthcare utilization, chemotherapy completion rate, and dose intensity according to sex.
Materials and Methods This is a sub-study of a multicenter cohort conducted in Korea that evaluated the impact of healthcare reimbursement on AE evaluation in patients who received adjuvant chemotherapy between September 2013 and December 2016 at four hospitals in Korea.
Results A total of 1,170 patients with colorectal, gastric, or non–small cell lung cancer were included in the study. Female patients were younger, had fewer comorbidities, and experienced less postoperative weight loss of > 10%. Females had significantly higher rates of any grade AEs including nausea, abdominal pain, stomatitis, vomiting, and neutropenia, and experienced more grade ≥ 3 neutropenia, nausea, and vomiting. The dose intensity of chemotherapy was significantly lower in females, and they also experienced more frequent dose reduction after the first cycle. Moreover, female patients receiving platinum-containing regimens had significantly higher rates of unscheduled outpatient visits.
Conclusion Our study found that females experienced a higher incidence of multiple any-grade AEs and severe neutropenia, nausea, and vomiting, across various cancer types, leading to more frequent dose reductions. Physicians should be aware of sex differences in AEs for chemotherapy decisions.
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Purpose There are clinical unmet needs in predicting therapeutic response and precise strategy for the patient with advanced biliary tract cancer (BTC). We aimed to identify genomic alterations predicting therapeutic response and resistance to gemcitabine and cisplatin (Gem/Cis)-based chemotherapy in advanced BTC.
Materials and Methods Genomic analysis of advanced BTC multi-institutional cohorts was performed using targeted panel sequencing. Genomic alterations were analyzed integrating patients’ clinicopathologic data, including clinical outcomes of Gem/Cis-based therapy. Significance of genetic alterations was validated using clinical next-generation sequencing (NGS) cohorts from public repositories and drug sensitivity data from cancer cell lines.
Results 193 BTC patients from three cancer centers were analyzed. Most frequent genomic alterations were TP53 (55.5%), KRAS (22.8%), ARID1A (10.4%) alterations, and ERBB2 amplification (9.8%). Among 177 patients with BTC receiving Gem/Cis-based chemotherapy, ARID1A alteration was the only independent predictive molecular marker of primary resistance showing disease progression for 1st-line chemotherapy in the multivariate regression model (odds ratio, 3.12; p=0.046). In addition, ARID1A alteration was significantly correlated with inferior progression-free survival on Gem/Cis-based chemotherapy in the overall patient population (p=0.033) and in patients with extrahepatic cholangiocarcinoma (CCA) (p=0.041). External validation using public repository NGS revealed that ARID1A mutation was a significant predictor for poor survival in BTC patients. Investigation of multi-OMICs drug sensitivity data from cancer cell lines revealed that cisplatin-resistance was exclusively observed in ARID1A mutant bile duct cancer cells.
Conclusion Integrative analysis with genomic alterations and clinical outcomes of the first-line Gem/Cis-based chemotherapy in advanced BTC revealed that patients with ARID1Aalterations showed a significant worse clinical outcome, especially in extrahepatic CCA. Well-designed prospective studies are mandatory to validate the predictive role of ARID1Amutation.
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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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Purpose Several previous studies and case reports have reported ethanol-induced symptoms in patients receiving anticancer drugs containing ethanol. Most docetaxel formulations contain ethanol as a solvent. However, there are insufficient data on ethanol-induced symptoms when docetaxel-containing ethanol is administered. The primary purpose of this study was to investigate the frequency and pattern of ethanol-induced symptoms during and after docetaxel administration. The secondary purpose was to explore the risk factors for ethanol-induced symptoms.
Materials and Methods This was a prospective, multicenter, observational study. The participants filled out ethanol-induced symptom questionnaire on the day of chemotherapy and the following day.
Results Data from 451 patients were analyzed. The overall occurrence rate of ethanol-induced symptoms was 44.3% (200/451 patients). The occurrence rate of facial flushing was highest at 19.7% (89/451 patients), followed by nausea in 18.2% (82/451 patients), and dizziness in 17.5% (79/451 patients). Although infrequent, unsteady walking and impaired balance occurred in 4.2% and 3.3% of patients, respectively. Female sex, presence of underlying disease, younger age, docetaxel dose, and docetaxel-containing ethanol amount were significantly associated with the occurrence of ethanol-induced symptoms.
Conclusion The occurrence of ethanol-induced symptoms was not low in patients receiving docetaxel-containing ethanol. Physicians need to pay more attention to the occurrence of ethanol-induced symptoms and prescribe ethanol-free or low-ethanol-containing formulations to high-risk patients.
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Purpose The benefit of adjuvant chemotherapy following curative-intent surgery in pancreatic ductal adenocarcinoma (PDAC) patients who had received neoadjuvant FOLFIRINOX is unclear. This study aimed to assess the survival benefit of adjuvant chemotherapy in this patient population.
Materials and Methods This retrospective study included 218 patients with localized non-metastatic PDAC who received neoadjuvant FOLFIRINOX and underwent curative-intent surgery (R0 or R1) between January 2017 and December 2020. The association of adjuvant chemotherapy with disease-free survival (DFS) and overall survival (OS) was evaluated in overall patients and in the propensity score matched (PSM) cohort. Subgroup analysis was conducted according to the pathology-proven lymph node status.
Results Adjuvant chemotherapy was administered to 149 patients (68.3%). In the overall cohort, the adjuvant chemotherapy group had significantly improved DFS and OS compared to the observation group (DFS: median, 13.8 months [95% confidence interval (CI), 11.0 to 19.1] vs. 8.2 months [95% CI, 6.5 to 12.0]; p < 0.001; and OS: median, 38.0 months [95% CI, 32.2 to not assessable] vs. 25.7 months [95% CI, 18.3 to not assessable]; p=0.005). In the PSM cohort of 57 matched pairs of patients, DFS and OS were better in the adjuvant chemotherapy group than in the observation group (p < 0.001 and p=0.038, respectively). In the multivariate analysis, adjuvant chemotherapy was a significant favorable prognostic factor (vs. observation; DFS: hazard ratio [HR], 0.51 [95% CI, 0.36 to 0.71; p < 0.001]; OS: HR, 0.45 [95% CI, 0.29 to 0.71; p < 0.001]).
Conclusion Among PDAC patients who underwent surgery following neoadjuvant FOLFIRINOX, adjuvant chemotherapy may be associated with improved survival. Randomized studies should be conducted to validate this finding.
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Cancer Res Treat. 2023;55(3):746-757. Published online February 9, 2023
Purpose We aimed to assess the humoral response to and reactogenicity of coronavirus disease 2019 (COVID-19) vaccination according to the vaccine type and to analyze factors associated with immunogenicity in actively treated solid cancer patients (CPs).
Materials and Methods Prospective cohorts of CPs, undergoing anticancer treatment, and healthcare workers (HCWs) were established. The participants had no history of previous COVID-19 and received either mRNA-based or adenovirus vector–based (AdV) vaccines as the primary series. Blood samples were collected before the first vaccination and after 2 weeks for each dose vaccination. Spike-specific binding antibodies (bAbs) in all participants and neutralizing antibodies (nAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type, Delta, and Omicron variants in CPs were analyzed and presented as the geometric mean titer.
Results Age-matched 20 HCWs and 118 CPs were included in the analysis. The bAb seroconversion rate and antibody concentrations after the first vaccination were significantly lower in CPs than in HCWs. After the third vaccination, antibody levels in CPs with a primary series of AdV were comparable to those in HCWs, but nAb titers against the Omicron variant did not quantitatively increase in CPs with AdV vaccine as the primary series. The incidence and severity of adverse reactions post-vaccination were similar between CPs and HCWs.
Conclusion CPs displayed delayed humoral immune response after SARS-CoV-2 vaccination. The booster dose elicited comparable bAb concentrations between CPs and HCWs, regardless of the primary vaccine type. Neutralization against the Omicron variant was not robustly elicited following the booster dose in some CPs, implying the need for additional interventions to protect them from COVID-19.
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