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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: 30 June 2026 | Viewed by 12120

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Special Issue Editors

Dr. Yuichi Saito

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Guest Editor

Department of Thoracic Surgery, Faculty of Medicine, Teikyo University School of Medicine, Tokyo 173-8605, Japan
Interests: thoracic malignancy; small lung cancer; intraoperative localization; VATS; minimally invasive surgery; surgical pathology
Special Issues, Collections and Topics in MDPI journals

Dr. Hiroyuki Adachi

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Guest Editor

Division of Thoracic Surgery, Department of Surgery, Yokohama City University, Yokohama 236-0004, Japan
Interests: thoracic malignancy; non-small-cell lung cancer; perioperative therapy; minimally invasive surgery; combined resection and reconstruction; bronchoplasty

Special Issue Information

Dear Colleagues,

Clinical research has come to play an increasingly important role in all malignant diseases, including thoracic cancer. For a long time, cancer treatments designed for the “average patient” based on the TNM classification have been used as a method for objectively describing the progression of cancer. These conventional treatments may be effective for some patients but have little effect on others. In the last 20 years, molecular biological techniques have proven that cancer is caused by an accumulation of genetic abnormalities; in other words, cancer has come to be considered a type of genetic disease. Precision medicine is a new medical concept in which treatment takes into account individual differences in genetic information, and genomic testing has been shown to be useful as a predictor of cancer treatment.

The advent of immunotherapy and molecular target drugs has significantly changed the treatment scheme for patients with thoracic cancers. In recent years, the introduction of these drugs into the perioperative period has become a hot topic even in the field of thoracic cancer, and some indications of treatment for thoracic cancer have changed significantly. Here, the purpose of this Special Issue is to understand the results of the latest clinical research to provide exciting changes for treatment strategies in thoracic cancer. This Special Issue welcomes reviews as well as original research articles by 6 June 2025.

Dr. Yuichi Saito
Dr. Hiroyuki Adachi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

thoracic cancer
lung cancer
thymic cancer
malignant mesothelioma
radiotherapy
surgery
chemotherapy
immunotherapy
driver mutation

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Published Papers (7 papers)

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Research

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16 pages, 3012 KB

Open AccessArticle

Association Between Neutrophil Percentage-to-Albumin Ratio (NPAR) and the Prognosis of Non-Small-Cell Lung Cancer

by Xin Ye, Yi Liu, Fanjie Meng, Bin Hu and Hui Li

Cancers 2026, 18(8), 1283; https://doi.org/10.3390/cancers18081283 - 18 Apr 2026

Viewed by 502

Abstract

Objective: This study investigates the prognostic value and clinical utility of the neutrophil percentage-to-albumin ratio (NPAR) in patients with resected non-small-cell lung cancer (NSCLC). Methods: We retrospectively included 335 patients with NSCLC who underwent lung resection at our institution between January 2017 and October 2018. Optimal cutoffs for preoperative and postoperative day 1 (D1) NPAR were determined using X-tile (version 3.6.1; Yale University, New Haven, CT, USA) to define high and low groups. Overall survival (OS) was evaluated using Kaplan–Meier analysis and Cox proportional hazards models. A perioperative NPAR trajectory (low–low, low–high, high–low, high–high) was constructed to characterize dynamic risk patterns. To mitigate potential bias associated with postoperative measurements, a D1 landmark analysis was performed. A nomogram was developed based on the multivariable model and assessed by calibration at 1, 3, and 5 years. Incremental clinical value beyond TNM stage and surgical approach was evaluated using decision curve analysis (DCA), as well as by 5-year continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results: The optimal cutoffs for preoperative and postoperative D1 NPAR were 14.5 and 23.1, respectively. In univariate analyses, sex, smoking history, preoperative NPAR, postoperative D1 NPAR, pathologic type, TNM stage, surgical approach, and adjuvant therapy were associated with OS (all p < 0.01). In multivariable Cox regression, high preoperative NPAR (HR 1.896, 95% CI 1.135–3.168; p = 0.014) and high postoperative D1 NPAR (HR 1.905, 95% CI 1.097–3.305; p = 0.014) were independent risk factors, along with TNM stage (Stage II: HR 2.824, 95% CI 1.209–6.595; p = 0.016; Stage III: HR 9.470, 95% CI 4.935–18.171; p < 0.001) and open surgery (HR 2.350, 95% CI 1.341–4.117; p = 0.003). Trajectory analysis further stratified risk, with the high–high group showing the poorest survival (adjusted HR 3.48, 95% CI 1.43–8.47; p = 0.006). The association of postoperative NPAR persisted in the D1 landmark analysis (HR 1.836, 95% CI 1.071–3.148; p = 0.027). Adding NPAR to TNM stage and surgical approach improved 5-year risk reclassification (continuous NRI 0.377, 95% CI 0.094–0.659; IDI 0.028, 95% CI −0.002–0.054) and increased net benefit on DCA. The nomogram demonstrated acceptable calibration at 1, 3, and 5 years. Conclusions: This study demonstrates that NPAR serves as an independent prognostic marker for long-term outcomes in patients with NSCLC. The use of NPAR offers clinicians a comprehensive and precise tool for assessing patient prognosis. Full article

(This article belongs to the Special Issue Clinical Research on Thoracic Cancer)

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15 pages, 2723 KB

Open AccessArticle

Response-Adapted Benefit of Postoperative Adjuvant Therapy Following Neoadjuvant Treatment in Resectable NSCLC: A Single-Center Retrospective Cohort Study

by Yanbo Wang, Weiran Zhang, Xin Wang, Han Zhang, Qiuqiao Mu, Jianyu Wang, Qingsheng Liu, Guotai Wang, Xin Li and Daqiang Sun

Cancers 2026, 18(6), 955; https://doi.org/10.3390/cancers18060955 - 15 Mar 2026

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Abstract

Background: Neoadjuvant immunochemotherapy improves pathological response in resectable non-small cell lung cancer (NSCLC), but the need and intensity of postoperative adjuvant therapy across different pathological response rate (PRR) strata remain uncertain. Methods: In this single-center retrospective cohort, 105 patients with resectable NSCLC received neoadjuvant platinum-based chemotherapy with or without PD-1/PD-L1 inhibitors followed by R0 resection. PRR was defined as 1—residual viable tumor fraction and categorized as 0–60%, 60–90%, and ≥90% (major pathological response, MPR). Postoperative strategies included no further therapy, chemotherapy alone, or immunotherapy ± chemotherapy. Event-free survival (EFS) was analyzed using Kaplan–Meier estimates, multivariable Cox models, and restricted cubic spline-based treatment × PRR interaction. Results: Deeper PRR was associated with lower ypT/ypN stage and improved EFS. In the PRR 0–60% subgroup, immunotherapy-containing adjuvant regimens were associated with better EFS, whereas chemotherapy alone did not outperform observation. In the PRR 60–90% and MPR strata, EFS curves for different postoperative strategies largely overlapped, and in MPR patients, hazard ratios were close to 1. Interaction modeling suggested that the absolute 3-year EFS benefit of immunochemotherapy peaked at intermediate PRR (≈60–80%) and diminished as PRR approached ≥90%. Conclusions: The robustness of these findings was further confirmed through a sensitivity analysis focusing on a homogeneous cohort of clinical stage II-III patients receiving adjuvant therapy. Among NSCLC patients treated with neoadjuvant systemic therapy, PRR is a strong prognostic marker and modulates the benefit of postoperative immunotherapy. These data support a response-adapted strategy, with adjuvant immunotherapy intensification in low-PRR patients and potential de-escalation or surveillance alone in MPR patients, warranting validation in prospective PRR-stratified trials. Full article

(This article belongs to the Special Issue Clinical Research on Thoracic Cancer)

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12 pages, 1328 KB

Open AccessArticle

Prognostic Impact of Baseline Neutrophil-to-Lymphocyte Ratio and Its On-Treatment Change on Survival Outcomes in Advanced Small-Cell Lung Cancer: A Retrospective Analysis

by Masashi Ishihara, Hao Chen, Reina Asaga, Hikaru Suzuki, Shinichiro Yamamoto, Maju Kawamoto, Hitoshi Hoshiya, Hiroki Kazahari, Ryosuke Ochiai, Shigeru Tanzawa, Takeshi Honda, Yasuko Ichikawa, Kiyotaka Watanabe and Nobuhiko Seki

Cancers 2026, 18(4), 671; https://doi.org/10.3390/cancers18040671 - 18 Feb 2026

Viewed by 706

Abstract

Background: Reliable and readily accessible prognostic biomarkers for extensive-stage small-cell lung cancer (ES-SCLC) are still lacking. The neutrophil-to-lymphocyte ratio (NLR), a marker of systemic inflammation, has shown prognostic relevance in several malignancies; however, its dynamic changes during treatment have not been well characterized in SCLC. Methods: We retrospectively analyzed patients with ES-SCLC who received systemic chemotherapy between January 2010 and December 2024. Baseline NLR was calculated within 7 days before first-line treatment, and on-treatment NLR was assessed at 6 weeks. A predefined NLR cutoff value of 5 was applied, and changes in NLR (ΔNLR) were defined as the difference between 6-week and baseline values. Associations with time to treatment failure (TTF) and overall survival (OS) were evaluated. Results: A total of 176 patients were enrolled. High baseline NLR (≥5) was significantly associated with shorter TTF and OS (both p < 0.01). An increase in NLR during treatment (ΔNLR ≥ 0) was significantly associated with poorer OS. Combined assessment of baseline NLR and ΔNLR identified distinct prognostic groups, with patients exhibiting both high baseline NLR and ΔNLR ≥ 0 demonstrating markedly poor survival. In multivariate analyses, baseline NLR, ΔNLR, performance status, and immune checkpoint inhibitor combination therapy were independent predictors of survival. Baseline NLR analyzed as a continuous variable showed a significant inverse correlation with TTF and OS. Conclusions: Combined evaluation of baseline NLR and its on-treatment change provides improved prognostic stratification in patients with ES-SCLC. Full article

(This article belongs to the Special Issue Clinical Research on Thoracic Cancer)

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15 pages, 3072 KB

Open AccessArticle

Neoadjuvant Concurrent Chemoradiotherapy Versus Neoadjuvant Chemotherapy in Thymic Epithelial Tumors: A Propensity Score-Matched Analysis

by Bubse Na, Chang Hyun Kang, Taeyoung Yun, Ji Hyeon Park, Kwon Joong Na, Samina Park, Hyun Joo Lee, In Kyu Park, Young Tae Kim, Bhumsuk Keam and Hak Jae Kim

Cancers 2026, 18(1), 85; https://doi.org/10.3390/cancers18010085 - 27 Dec 2025

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Abstract

Background: Neoadjuvant chemotherapy is generally recommended for locally advanced, potentially resectable thymic epithelial tumors. However, neoadjuvant chemoradiotherapy has been proposed as an alternative approach, potentially achieving higher complete resection rates. In this study, a retrospective analysis was conducted to compare the outcomes of neoadjuvant chemoradiotherapy (NCRT) and neoadjuvant chemotherapy (NCT). Methods: From 2009 to 2022, a total of 98 patients who underwent surgery following either NCRT (n = 30) or NCT (n = 68) for thymic epithelial tumors were included in this study. Propensity score matching was applied, resulting in two matched groups of 30 patients each. The primary endpoint was the comparison of complete (R0) resection rates between the groups. Results: In the matched cohort, the R0 resection rate was significantly higher in the NCRT group (93.3%) compared to the NCT group (73.3%; p = 0.038). The tumor regression grade was also significantly lower in the NCRT group (p = 0.002). However, no significant difference was observed in 5-year overall survival between the groups, either in patients with thymoma (100% for NCRT vs. 90.9% for NCT; p = 0.34) or thymic carcinoma (74.3% for NCRT vs. 63.2% for NCT; p = 0.82). For patients with initial local recurrence, both the 5-year overall survival and post-recurrence survival rates were 100%. Conclusions: The neoadjuvant chemoradiotherapy group demonstrated superior local control, as evidenced by improved tumor regression grades and complete resection rates. However, the absence of corresponding improvement in overall survival warrants further investigation with a larger patient cohort and a longer follow-up period. Full article

(This article belongs to the Special Issue Clinical Research on Thoracic Cancer)

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14 pages, 1360 KB

Open AccessArticle

Multicenter Prospective Comparative Study of Patient Radiation Doses in Localization Techniques for Small Lung Lesions

by Tomoki Nishida, Yuichi Saito, Takeshi Takata, Shizuka Morita, Ryo Takeyama, Shinya Kohmaru, Tomohiro Watanabe, Nobuo Yamaguchi, Hikaru Takahashi, Yasuyuki Kanamoto, Hiroaki Morooka, Takayuki Ibi, Yoshikane Yamauchi, Ryuta Fukai, Nobumasa Takahashi, Tetsu Kanauchi, Ikuo Kobayashi, Masafumi Kawamura and Yukinori Sakao

Cancers 2025, 17(19), 3119; https://doi.org/10.3390/cancers17193119 - 25 Sep 2025

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Abstract

Background/Objectives: Although surgeries employing cone-beam computed tomography (CBCT) for small lung lesions have been reported, the association between CBCT scan frequency and patient radiation exposure remains unclear. This study aimed to investigate patient radiation doses from CBCT during thoracic surgeries, and the patient radiation doses were compared with those from other preoperative marking methods. Methods: This multicenter prospective study included 81 patients who underwent surgery for small lung lesions requiring marking between January 2021 and June 2024 at three institutions. CBCT-guided surgeries involved the use of metal clips in a hybrid operating room with 1–4 scans, depending on the lesion. For other preoperative marking methods, hook-wire or virtual-assisted lung mapping (VAL-MAP) was used. Patient radiation doses were measured using wearable dosimeters at five anterior thorax sites, and the total dose was compared across methods. Results: The study included 81 patients: CBCT (n = 61), VAL-MAP (n = 10), and hook-wire (n = 10). CBCT cases were distributed as follows: single scan (n = 10), double scans (n = 34), triple scans (n = 15), and quadruple scans (n = 2). The radiation doses were 86.9 ± 61.7 mGy for hook-wire, 39.8 ± 27.5 mGy for VAL-MAP, and 11.0 ± 6.5 mGy for single-scan CBCT, 17.3 ± 7.8 mGy for double scans, 23.1 ± 14.0 mGy for triple scans, and 22.7 ± 0.1 mGy for quadruple scans. Although radiation exposure increased with more CBCT scans, performing up to triple scans resulted in significantly lower exposure compared to other methods. Conclusions: Intraoperative CBCT is a feasible and safe technique for identifying small lung lesions, providing lower radiation exposure compared to other preoperative localization methods. Full article

(This article belongs to the Special Issue Clinical Research on Thoracic Cancer)

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14 pages, 1120 KB

Open AccessArticle

Temporal Trends of Hyponatremia in Patients with Respiratory and Intrathoracic Cancers Treated with Chemotherapy and Immune Checkpoint Inhibitors

by Kuo-Cheng Lu, Ching-Liang Ho, Joshua Wang, Cai-Mei Zheng, Kuo-Wang Tsai, Yi-Chou Hou and Chien-Lin Lu

Cancers 2025, 17(9), 1459; https://doi.org/10.3390/cancers17091459 - 26 Apr 2025

Cited by 2 | Viewed by 2599

Abstract

Background: Immune checkpoint inhibitors (ICIs) offer a novel approach to cancer treatment by enhancing immune responses against malignant cells. However, ICIs are associated with immune-related adverse events (irAEs), including hyponatremia, a potentially severe electrolyte disturbance. The risk of hyponatremia increases further when ICIs are combined with cisplatin, a nephrotoxic chemotherapy agent widely used in treating respiratory and intrathoracic cancers. This study investigated the incidence, severity, and temporal dynamics of hyponatremia in patients treated with ICIs alone or in combination with cisplatin. Methods: A retrospective cohort study was conducted using data from the TriNetX global health research network. Patients with respiratory or intrathoracic malignancies (n = 14,026) were divided into two groups: ICI-only (n = 7013) and ICI with cisplatin combination (n = 7013), matched using propensity scores. Hyponatremia was categorized into mild (130–134 mmol/L), moderate (125–129 mmol/L), and severe (<125 mmol/L). Temporal trends and cumulative incidence over 90 days were analyzed using Poisson regression. Results: The combination group exhibited a higher cumulative incidence of hyponatremia across all severity levels, with early-phase risk peaking within 20 days of treatment. Rate ratios for mild, moderate, and severe hyponatremia were significantly elevated in the combination group (p < 0.01). Conclusions: Hyponatremia is a significant complication in patients receiving ICIs, particularly when combined with cisplatin. Early monitoring and tailored management are essential to mitigate risks and optimize treatment outcomes. Full article

(This article belongs to the Special Issue Clinical Research on Thoracic Cancer)

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Review

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35 pages, 434 KB

Open AccessReview

The Evolving Role of Chemotherapy in the Management of Pleural Malignancies: Current Evidence and Future Directions

by Yuliya Semenova, Zhandos Burkitbayev, Nurtas Kalibekov, Alexandr Digay, Bakhyt Zhaxybayev, Oxana Shatkovskaya, Saule Khamzina, Dinara Zharlyganova, Zhuldyz Kuanysh and Almira Manatova

Cancers 2025, 17(13), 2143; https://doi.org/10.3390/cancers17132143 - 25 Jun 2025

Cited by 2 | Viewed by 4750

Abstract

Pleural malignancies represent a clinically devastating group of oncological disorders, most commonly arising from metastatic disease, with lung and breast cancers being the most frequent primary sites. Malignant pleural mesothelioma is a primary malignancy of the pleura and occurs less often than metastatic pleural disease. Pleural malignancies often present with malignant pleural effusion, which typically indicates advanced-stage disease and is associated with poor overall prognosis. Treatment of pleural malignancies includes both palliative and definitive approaches. Palliative interventions primarily aim to relieve symptoms and improve quality of life. Definitive treatments include systemic chemotherapy, targeted therapy, and immunotherapy, depending on the type and molecular profile of the underlying tumor. In mesothelioma, platinum-based chemotherapy in combination with pemetrexed remains the cornerstone of treatment, while the combination of nivolumab and ipilimumab is recommended as first-line therapy for unresectable disease. For metastatic disease, systemic therapy is typically tailored to the primary tumor’s characteristics. Intrapleural administration of chemotherapeutic agents is one of the therapeutic strategies and hyperthermic intrathoracic chemotherapy and pressurized intrathoracic aerosol chemotherapy are the most recent innovations that are under active investigation. This review provides an up-to-date synthesis of systemic chemotherapy strategies for pleural malignancies, their integration with targeted and immune-based therapies, and recent advances in intrapleural chemotherapy modalities. It also explores existing knowledge gaps and outlines directions for future research and potential changes in clinical practice. Full article

(This article belongs to the Special Issue Clinical Research on Thoracic Cancer)

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