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Cancers, Volume 18, Issue 1 (January-1 2026) – 5 articles

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17 pages, 2036 KB

Open AccessReview

Pharmacokinetic and Pharmacodynamic Modeling of Antibody-Drug Conjugates

by Patrick M. Glassman

Cancers 2026, 18(1), 5; https://doi.org/10.3390/cancers18010005 (registering DOI) - 19 Dec 2025

Abstract

Antibody-drug conjugates (ADCs) have risen in prominence over the past 15 years, with numerous regulatory approvals in oncology. A complicating factor in the development of ADCs is the presence of numerous analytes with unique pharmacologic properties. Following administration, ADCs are present in the body as the intact ADC, unconjugated antibody, and liberated payload. Due to heterogeneity in conjugation and in vivo deconjugation rates, the drug-to-antibody ratio (DAR) changes with time. Each of these molecular species has unique pharmacokinetic (PK) and pharmacodynamic (PD) properties that should be understood and characterized. One approach that is frequently applied is the development of in silico mathematical models to characterize and predict the PK/PD of ADCs. In this review, we summarize key mechanisms controlling the PK/PD of ADCs. This provides context for a detailed discussion of the array of PK/PD models that have been applied for ADCs, ranging from empirical compartmental models all the way through system-level models, such as physiologically based pharmacokinetics (PBPK) and cell-level PK/PD models. We provide a critical discussion of the strengths, weaknesses, and utility of each of these model structures. Full article

(This article belongs to the Special Issue Advances in Antibody–Drug Conjugates (ADCs) in Cancers)

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26 pages, 538 KB

Open AccessArticle

Surgical Treatment Options for Renal Cell Carcinoma Metastases to the Pancreas—25 Years of Single-Center Experience

by Magdalena Gajda, Ewa Grudzińska, Paweł Szmigiel, Paweł Sasiński and Sławomir Mrowiec

Cancers 2026, 18(1), 4; https://doi.org/10.3390/cancers18010004 (registering DOI) - 19 Dec 2025

Abstract

Background: Clear cell renal cell carcinoma (RCC) is the most common primary tumor that metastasizes to the pancreas, and surgery is the established treatment option. The aim of this study was to compare surgical treatment options for RCC metastases to the pancreas and to assess long-term outcomes, identifying risk factors for recurrence and death. Methods: We retrospectively analyzed data from 62 patients with RCC metastases to the pancreas who underwent pancreatic surgery at the Department of Gastrointestinal Surgery, Medical University of Silesia, Katowice. Patients were divided into two groups: those who underwent local tumor removal (group A, N = 10) and those who underwent classical pancreatic resection (group B, N = 52). Demographic data, postoperative course, histological findings, and clinical outcomes—recurrence-free survival (PFS) and overall survival (OS)—were analyzed. Results: In group A, tumors were smaller (p < 0.001) and exclusively single (p = 0.100), and Clavien–Dindo complications were milder, with a predominance of grade 0 (90% vs. 28.8%; p = 0.042). In group B, blood loss was greater (p < 0.001), and hospitalization was longer (median 12.5 days vs. 10.5 days; p = 0.022) compared with group A. Group A had a longer PFS (144 months vs. 61 months; p = 0.007) and longer OS (144 months vs. 70 months; p = 0.006) compared with group B. In the entire cohort, independent factors associated with worse OS in multivariate analysis were larger tumor size (p = 0.003), lymphatic invasion (p < 0.001), vascular invasion (p < 0.001), perineural invasion (p < 0.001), R1 resection (p < 0.001), and symptoms of the metastases (p < 0.001). Conclusions: The prognosis following surgical resection of pancreatic RCC metastases is excellent: median OS is 77 months, and 5-year survival reaches 71.4%. In multivariate analysis, the type of surgical treatment is not significantly associated with OS or PFS. The choice of surgical procedure should depend on the preoperative CT results and the intraoperative assessment of the surrounding tissues. Full article

(This article belongs to the Special Issue Surgery in Metastatic Cancer (2nd Edition))

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12 pages, 603 KB

Open AccessArticle

Patient-Reported Financial Burden in Head and Neck Cancer Undergoing Radiotherapy

by Renata Zahu, Monica Emilia Chirila, Otilia Ciobanu, Daniela Elena Sturzu, Andrei Ciobanu, Gabriela Ciobanu, Noemi Besenyodi, Madalina Vesel-Pop, Flavius Coșer, Roxana Costache and Gabriel Kacso

Cancers 2026, 18(1), 3; https://doi.org/10.3390/cancers18010003 (registering DOI) - 19 Dec 2025

Abstract

Background/Objectives: Financial toxicity (FT) refers to the financial burden directly or indirectly caused by a patient’s medical care. Patients with head and neck cancer (HNC) are particularly vulnerable to FT due to lower rates of return to work and higher out-of-pocket payments (OOPP). In this cross-sectional study, we assessed the amount and types of OOPP, as well as the prevalence of FT, in HNC patients who had completed curative radiotherapy. Methods: We included HNC patients who underwent curative-intent radiotherapy at four private clinics in Romania, within 12 months of completing treatment. Participants completed a 25-item questionnaire capturing sociodemographic information, insurance status, income, and OOPP. To assess subjective FT, we used the validated nine-item Financial Index of Toxicity (FIT), which measures three FT domains: financial stress, financial strain, and lost productivity. Each domain and the total score range from 0 to 100, with higher scores indicating greater financial toxicity. Descriptive statistics were used to summarize patient characteristics. Pearson’s chi-square, t-tests, and one-way ANOVA were used to assess statistical associations, with a significance threshold of p < 0.05. Results: Among 113 patients (mean age: 59), the majority were male (74.3%) and married (74.3%), with 40% having completed university or higher education. The most frequent tumor sites were the oropharynx (29 cases), larynx (22), and oral cavity (21). Concurrent chemoradiation was the most common treatment modality (47%). The mean total FT score was 18.8. Overall, 39.8% of patients experienced financial toxicity, and 29.2% scored above the mean in financial stress. Moderate financial strain (score > 21) was reported by 39.8% of participants, and approximately one-third reported loss of productivity. Transportation and nutritional supplements were the most common OOPP categories. Notably, 42% of patients spent at least 400 euros—equivalent to Romania’s monthly minimum income—on transportation during radiotherapy. FT was significantly associated with employment and marital status, but not with tumor site or treatment type. Conclusions: Among Romanian HNC patients treated with curative radiotherapy, we found substantial OOPP, particularly for transportation and nutritional supplements. While overall FT levels were moderate, divorced patients and those retired due to other chronic conditions were the most vulnerable to financial distress. Financial toxicity can directly affect treatment adherence, survival, and quality of life. By integrating financial counseling, social support, and broader coverage of treatment-related expenses, healthcare systems can mitigate FT for these patients. Full article

(This article belongs to the Special Issue Advances in Radiation Therapy for Head and Neck Cancer)

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13 pages, 248 KB

Open AccessArticle

Risk Assessment for Malignant Transformation in Patients with Oral Proliferative Leukoplakia: A 10-Year Retrospective Cohort Study

by Gianluca Tenore, Ahmed Mohsen, Paolo Junior Fantozzi, Andrea Golrang, Gian Marco Podda, Federica Rocchetti, Lucia Borghetti, Laura Sansotta, Cira Rosaria Tiziana Di Gioia and Umberto Romeo

Cancers 2026, 18(1), 2; https://doi.org/10.3390/cancers18010002 (registering DOI) - 19 Dec 2025

Abstract

Objectives: This study aimed to evaluate the malignant transformation (MT) risk profile in patients with oral proliferative leukoplakia (OPL) referred to the Oral Medicine and Oral Surgery units of Umberto I Hospital, Sapienza University of Rome. Methods: The departmental database and medical records of OPL patients were reviewed from January 2014 to June 2024. Demographic, clinical, and histopathological features and treatment strategies were collected in a de-identified dataset. Results: A total of 51 OPL patients (33 females and 18 males; mean age 62.86 ± 13.55 years) were included. MT occurred in 17.6% (n = 9) after a mean follow-up of 4.78 ± 2.59 years. A higher percentage of the presence of a previous history of solid or hematological tumor was observed in patients with MT, with an OR of 2.940 (95% CI 0.064–1.350), without statistical significance. The homogeneous clinical form was more common in patients without MT (78.57%), and the speckled clinical form was more common in patients with MT (44.44%). The percentage of patients with lesions located on the floor of the mouth, ventral surface of the tongue, and dorsal surface of the tongue was higher in patients with MT. The tongue was the most common site of MT, followed by the gingiva, buccal mucosa, and palate. At the histological level, a verrucous, nodular, or bulky architecture was more commonly observed in patients with MT, and the presence of band-like lymphocytic infiltrate was observed in all patients with MT. Higher dysplasia grades were significantly associated with MT (p = 0.009). No significant association was found between the treatment modality and MT risk, although laser ablation was associated with a trend toward lower risk. Conclusions: This study further suggests that the clinical morphology, lesion site, and histological grading may be important predicting factors for MT in OPL. The presence of a non-homogeneous lesion form, a higher grade of dysplasia, and a history of previous solid or hematological tumor led to a more aggressive disease course. Individualized risk assessment and long-term surveillance may be advisable. Full article

(This article belongs to the Special Issue Oral Cancer: Prevention and Early Detection (2nd Edition))

12 pages, 1020 KB

Open AccessArticle

Response Prediction of Chemoradiotherapy for Rectal Cancer Using Rapid Semi-Automated Flow Cytometry

by Hiroyuki Amagai, Koichi Hayano, Takahiro Shioyama, Akane Suzuki, Gaku Ohira, Tetsuro Maruyama, Toru Tochigi, Koichiro Okada, Takahiro Arasawa, Nobufumi Sekino, Ryoya Mizumachi, Soichiro Hirasawa, Masaya Uesato, Michihiro Maruyama, Yoshihiro Kurata, Atsushi Hirata and Hisahiro Matsubara

Cancers 2026, 18(1), 1; https://doi.org/10.3390/cancers18010001 (registering DOI) - 19 Dec 2025

Abstract

(1) Background: The effectiveness of chemoradiotherapy (CRT) for rectal cancer varies greatly among patients, and no reliable biomarker for predicting treatment response currently exists. We investigated whether cell cycle analysis using rapid semi-automated flow cytometry could predict the effectiveness of CRT. (2) Methods: This prospective study included 32 patients with rectal cancer undergoing CRT. The cell cycle of biopsy specimens from rectal cancer patients before CRT was semi-automatically and rapidly analyzed using Celltac PEAK as flow cytometer. The proportion of cell cycle phases is compared with treatment response after CRT. (3) Results: Patients with a tumor reduction rate ≥ 30% on CT showed a significantly higher proportion of cells in the Over G2/M phase compared with those with <30% reduction (median 2.45% vs. 0.95%, p = 0.022). Similarly, tumors demonstrating disappearance of FDG uptake after CRT had a significantly higher proportion of cells in the Over G2/M phase compared with those with persistent FDG uptake (median 4.05% vs. 1.24%, p = 0.024). (4) Conclusions: A high proportion of cells in the Over G2/M phase could be a potential biomarker for predicting tumor shrinkage in CRT for rectal cancer. Full article

(This article belongs to the Section Cancer Therapy)

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