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Cancers, Volume 18, Issue 2 (January-2 2026) – 19 articles

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17 pages, 284 KB  
Review
Minimally Invasive Pancreatoduodenectomy for Pancreatic Cancer: Current Perspectives and Future Directions
by Munseok Choi and Chang Moo Kang
Cancers 2026, 18(2), 197; https://doi.org/10.3390/cancers18020197 - 7 Jan 2026
Abstract
Background: Minimally invasive pancreatoduodenectomy (MIPD) has evolved from an experimental technique to a feasible surgical option for pancreatic cancer in selected settings. However, its oncologic adequacy, safety, and generalizability remain debated, particularly given the biological aggressiveness of pancreatic ductal adenocarcinoma (PDAC) and the [...] Read more.
Background: Minimally invasive pancreatoduodenectomy (MIPD) has evolved from an experimental technique to a feasible surgical option for pancreatic cancer in selected settings. However, its oncologic adequacy, safety, and generalizability remain debated, particularly given the biological aggressiveness of pancreatic ductal adenocarcinoma (PDAC) and the technical complexity of the procedure. Methods: This narrative review critically summarizes contemporary evidence regarding MIPD for pancreatic cancer, with particular attention to randomized controlled trials (RCTs), meta-analyses, and large observational studies. We distinguish findings derived from mixed periampullary tumor cohorts from those specific to PDAC and evaluate methodological limitations, learning-curve effects, and sources of heterogeneity across studies. Results: Recent RCTs and meta-analyses demonstrate that, when performed by experienced surgeons in high-volume centers, MIPD achieves perioperative outcomes comparable to open pancreatoduodenectomy, with advantages including reduced blood loss, shorter hospital stay, and faster functional recovery. Importantly, oncologic parameters such as R0 resection rates and lymph node yield appear equivalent between approaches, although robust long-term survival data from PDAC-specific RCTs remain lacking. Emerging evidence supports the feasibility of MIPD in complex clinical scenarios, including after neoadjuvant therapy, in frail or elderly patients, and in selected cases requiring vascular resection. Nonetheless, outcomes are strongly influenced by surgeon experience, institutional volume, and patient selection. Cost-effectiveness analyses and data from lower-volume centers remain limited. Conclusions: Current evidence supports MIPD as a viable alternative to open surgery for pancreatic cancer in carefully selected patients treated at specialized centers. However, claims of oncologic superiority are premature. Future research should focus on PDAC-specific randomized trials, standardized quality metrics, and strategies to mitigate learning-curve and resource-related barriers to broader implementation. Full article
(This article belongs to the Special Issue Advances in Pancreatoduodenectomy)
12 pages, 3854 KB  
Article
Crosstalk of Tumor-Derived Extracellular Vesicles with Immune Recipient Cells and Cancer Metastasis
by Han Jie, Alicja C Gluszko and Theresa L. Whiteside
Cancers 2026, 18(2), 196; https://doi.org/10.3390/cancers18020196 - 7 Jan 2026
Abstract
Background. Contributions of tumor-derived extracellular vesicles, TEX, to tumor progression and metastasis involve their crosstalk with immune cells in the tumor microenvironment. This crosstalk results in metabolic reprogramming of immune cells from anti-tumor to pro-tumor activity. Mechanistic underpinnings of the TEX entry [...] Read more.
Background. Contributions of tumor-derived extracellular vesicles, TEX, to tumor progression and metastasis involve their crosstalk with immune cells in the tumor microenvironment. This crosstalk results in metabolic reprogramming of immune cells from anti-tumor to pro-tumor activity. Mechanistic underpinnings of the TEX entry and delivery of molecular signals responsible for metabolic reprogramming may be unique for different types of immune cells. Methods. An in vitro model of THP-1 myeloid cells co-incubated with TEX illustrates the role TEX play in polarization of macrophages to TAMs. Results. In THP-1 cells, the dominant signaling pathway of melanoma cell-derived TEX involves HSP-90/TLR2. This leads to activation of the NF-κB and MAP kinase pathways and initiates THP-1 cell polarization from M0 to M2 with strong expression of immunosuppressive PD-L1. TEX may be seen as “danger” by the myeloid cells, which utilize the pattern recognition receptors (PRR), such as PAMPs or DAMPs, for engaging the complementary ligands carried by TEX. The same melanoma TEX signaling to T cells via DAMPs induced mitochondrial stress, resulting in T-cell apoptosis. Conclusions. As the signaling receptors/ligands in TEX are determined by the tumor, it appears that the tumor equips TEX with an address recognizing specific PRRs expressed on different recipient immune cells. Thus, TEX, acting like pathogens, are equipped by the tumor to alter the context of intercellular crosstalk and impose a distinct autophagy-not-apoptosis signature in recipient THP-1 cells. The tumor might endorse TEX to promote tumor progression and metastasis by enabling them to engage the signaling system normally used by immune cells for defense against pathogens. Full article
(This article belongs to the Special Issue Exosomes in Cancer Metastasis (2nd Edition))
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26 pages, 353 KB  
Review
Nuclear Imaging in Renal Cell Carcinoma: Current Evidence and Clinical Applications
by Abdullah Al-Khanaty, Shane Qin, Carlos Delgado, David Hennes, Eoin Dinneen, David Chen, Lewis Au, Renu S. Eapen, Damien Bolton, Declan G. Murphy, Nathan Lawrentschuk, Gregory Jack, Daniel Moon, Michael S. Hofman and Marlon L. Perera
Cancers 2026, 18(2), 195; https://doi.org/10.3390/cancers18020195 - 7 Jan 2026
Abstract
Introduction: Radiotracer-based nuclear imaging, including positron emission tomography (PET) and single-photon emission computed tomography (SPECT), can complement conventional cross-sectional imaging in renal cell carcinoma (RCC) by providing biological characterisation of tumour metabolism, angiogenesis, hypoxia, and the tumour microenvironment. While computed tomography (CT) and [...] Read more.
Introduction: Radiotracer-based nuclear imaging, including positron emission tomography (PET) and single-photon emission computed tomography (SPECT), can complement conventional cross-sectional imaging in renal cell carcinoma (RCC) by providing biological characterisation of tumour metabolism, angiogenesis, hypoxia, and the tumour microenvironment. While computed tomography (CT) and magnetic resonance imaging (MRI) remain the diagnostic standard, accumulating evidence suggests that selected nuclear imaging techniques may offer incremental value in specific clinical scenarios. Methods: A narrative literature review was performed using PubMed, Embase, and Web of Science to identify preclinical, retrospective, and prospective studies evaluating PET and SPECT radiotracers in localised and metastatic RCC. Priority was given to meta-analyses, multicentre prospective trials, and studies with histopathological correlation. Results: [18F]fluorodeoxyglucose (FDG) PET/CT demonstrates limited sensitivity for primary renal tumours (pooled sensitivity of approximately 60%) but performs substantially better in metastatic and recurrent disease (pooled sensitivity and specificity of approximately 85–90%), where uptake correlates with tumour grade, progression-free survival, and overall survival. [99mTc]sestamibi SPECT/CT differentiates oncocytoma and hybrid oncocytic/chromophobe tumours from malignant RCC with pooled sensitivity and specificity of around 85–90%, supporting its role in evaluating indeterminate renal masses rather than staging. Prostate-specific membrane antigen (PSMA) PET/CT shows high detection rates in clear-cell RCC, particularly in metastatic disease, with reported sensitivities of approximately 85–90% and management changes in up to 40–50% of selected cohorts. Carbonic anhydrase IX (CAIX)-targeted PET/CT enables the biologically specific visualisation of clear-cell RCC, achieving sensitivities and specificities in the range of 85–90% in prospective phase II and III trials for primary tumour characterisation. Fibroblast activation protein inhibitor (FAPI) PET/CT demonstrates high tumour-to-background uptake in early RCC studies, but evidence remains preliminary, with small cohorts and recognised non-specific uptake in benign inflammatory and fibrotic conditions. Conclusions: Radiotracer-based nuclear imaging provides complementary, biology-driven insights in RCC that extend beyond anatomical assessment. While most modalities remain adjunctive or investigational and are not recommended for routine use, selective application in carefully chosen clinical scenarios may enhance tumour characterisation, prognostication, and personalised treatment planning. Full article
(This article belongs to the Section Methods and Technologies Development)
21 pages, 713 KB  
Article
Prognostic Impact of Unplanned Hospitalization During First-Line Gemcitabine Plus Nab-Paclitaxel Therapy for Unresectable Pancreatic Cancer: A Single-Center Retrospective Observational Study
by Kazuki Watabe, Motoyasu Kan, Izumi Ohno, Sodai Uchida, Taiga Sudo, Koki Yokozuka, Akinori Abe, Yoshiki Nakaya, Yoshiki Ogane, Hiroki Kurosaki, Miho Sakai, Yu Sekine, Tomoya Takahashi, Mayu Ouchi, Hiroshi Ohyama, Nozomu Sakai, Shigetsugu Takano, Tsukasa Takayashiki, Masayuki Ohtsuka and Jun Kato
Cancers 2026, 18(2), 194; https://doi.org/10.3390/cancers18020194 - 7 Jan 2026
Abstract
Background: Pancreatic cancer (PC) is a refractory malignancy with a dismal prognosis. For unresectable PC, gemcitabine plus nab-paclitaxel (GnP) is widely used as first-line chemotherapy. During treatment, patients may require unplanned hospitalization (UPH) due to tumor progression, biliary obstruction, or chemotherapy-related adverse events. [...] Read more.
Background: Pancreatic cancer (PC) is a refractory malignancy with a dismal prognosis. For unresectable PC, gemcitabine plus nab-paclitaxel (GnP) is widely used as first-line chemotherapy. During treatment, patients may require unplanned hospitalization (UPH) due to tumor progression, biliary obstruction, or chemotherapy-related adverse events. Although UPH during chemotherapy may be linked to poorer survival, its prognostic impact as a time-dependent clinical event during active treatment has not been empirically evaluated in unresectable PC. We investigated the prognostic impact of UPH occurring during first-line GnP therapy. Objective: To clarify the association between UPH during first-line GnP and overall survival (OS). Methods: We retrospectively analyzed 189 patients with histologically confirmed unresectable PC who received first-line GnP at our institution between February 2016 and February 2023. The occurrence of UPH during GnP and the reason for the first UPH were categorized. Associations with OS were assessed using the Kaplan–Meier method and Cox proportional hazards models, including a time-varying covariate (TVC) analysis. Risk factors for UPH were examined with logistic regression. Results: UPH occurred in 76 patients (40.2%) during GnP. Pancreatic head tumors and pre-treatment biliary drainage were significantly more frequent in the UPH group. Median OS was 10.88 months in the UPH group versus 19.23 months in the non-UPH group; UPH was a significant adverse prognostic factor (hazard ratio [HR] 1.97, p < 0.01). In multivariable analysis incorporating a TVC, UPH remained an independent predictor of worse prognosis (HR 3.02, p < 0.01). Reasons for first UPH were progression (n = 28), recurrent biliary obstruction (RBO; n = 26), GnP-related adverse event (AE; n = 16), and other (n = 6). Hospitalization due to progression or RBO was associated with poorer survival. Pancreatic head location was identified as a risk factor for UPH. Conclusions: UPH during first-line GnP is an independent adverse prognostic factor in patients with unresectable PC, even after accounting for TVC. In pancreatic head cancer, closer monitoring for biliary and obstructive complications may be particularly important during treatment. Full article
(This article belongs to the Section Clinical Research of Cancer)
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10 pages, 220 KB  
Review
“Radiological Grading” for Preoperative Assessment of Central Cartilaginous Tumors
by Shinji Miwa, Katsuhiro Hayashi, Takashi Higuchi, Hirotaka Yonezawa, Sei Morinaga, Yohei Asano and Satoru Demura
Cancers 2026, 18(2), 193; https://doi.org/10.3390/cancers18020193 - 7 Jan 2026
Abstract
In the treatment of musculoskeletal tumors, surgeons sometimes experience discrepancies in the histological grade between the preoperative biopsy and resected tumor specimen, and the frequency of the histological discrepancies in cartilaginous tumors is higher than that in other bone tumors. For cartilaginous tumors, [...] Read more.
In the treatment of musculoskeletal tumors, surgeons sometimes experience discrepancies in the histological grade between the preoperative biopsy and resected tumor specimen, and the frequency of the histological discrepancies in cartilaginous tumors is higher than that in other bone tumors. For cartilaginous tumors, new diagnostic tools or methods for the prediction of histological grades are required to determine appropriate surgical procedures for each patient. Several radiological findings have been reported to be useful in differentiating benign cartilaginous tumors, atypical cartilaginous tumors/grade 1 chondrosarcomas, and high-grade chondrosarcomas. Furthermore, recent studies have shown the high accuracy of radiological scoring systems that integrate several radiological findings to predict the histological grades of cartilaginous tumors. Radiomics, which converts features in radiological images into quantitative data, enables the comprehensive analysis of cartilaginous tumors. Recent reports suggest that radiological diagnoses are highly reliable compared with preoperative histological diagnoses for predicting the final histological diagnosis. Based on previous reports, “radiological grading,” i.e., the prediction of histological aggressiveness using radiological modalities, can be important for determining the surgical procedure, in addition to “histological grading.” This review article discusses radiological findings, integrated radiological scoring systems, and radiomics-based predictions of histological grades in cartilaginous tumors. Full article
(This article belongs to the Special Issue Challenges and New Developments in the Diagnosis and Treatment of Sarcoma)
13 pages, 1957 KB  
Article
Combinatorial Analysis of CD4+Tregs, CD8+Teffs, and Inflammatory Indices Predict Response to ICI in ES-SCLC Patients
by Anastasia Xagara, Konstantinos Tsapakidis, Vassileios Papadopoulos, Alexandros Kokkalis, Evangelia Chantzara, Chryssovalantis Aidarinis, Alexandros Lazarou, George Christodoulopoulos, Matina Perifanou-Sotiri, Dimitris Verveniotis, Vasiliki Rammou, Maria Smaragdi Vlachou, Galatea Kallergi, Alexandra Markou, Ioannis Samaras, Filippos Koinis, Emmanouil Saloustros and Athanasios Kotsakis
Cancers 2026, 18(2), 192; https://doi.org/10.3390/cancers18020192 - 7 Jan 2026
Abstract
Background: Small-cell lung cancer (SCLC) is an aggressive type of lung cancer, and several factors are currently used to predict poor outcomes, including performance status (PS), extensive-stage disease, male sex, advanced age, and elevated lactate dehydrogenase (LDH) levels. In this study, we [...] Read more.
Background: Small-cell lung cancer (SCLC) is an aggressive type of lung cancer, and several factors are currently used to predict poor outcomes, including performance status (PS), extensive-stage disease, male sex, advanced age, and elevated lactate dehydrogenase (LDH) levels. In this study, we aimed to explore the role of Tegs and inflammatory indices, such as CRP and NLR, in predicting response to immunotherapy. Methods: Fifty-one therapy-naïve ES-SCLC patients and ten healthy donors were enrolled. Peripheral blood mononuclear cells (PBMCs) were isolated and stained with fluorochrome-conjugated monoclonal antibodies. Multicolor flow cytometry was performed to determine the levels of CD8+ T cells and CD4+ Tregs, as well as their correlation with inflammatory indices and clinical outcomes. Results: ES-SCLC patients harbored higher percentages of CD8+ Teffs (p = 0.005) and FOXP3+ Tregs (p < 0.0001) in circulation before therapy compared with healthy donors. In addition, high levels of CD3+CD8+ T effectors were associated with longer PFS (p = 0.018) and longer OS (p = 0.012) compared with patients bearing low levels, while Tregs were not found to be predictive. More importantly, a survival benefit was observed in ES-SCLC patients with a low Treg/Teff ratio, as longer OS was observed in those with high percentages of CD8+ Teffs and low FOXP3+CTLA-4+ Tregs (p = 0.014) compared with those bearing low CD8+ Teffs and high FOXP3+CTLA-4+ Tregs. A low Treg/Teff ratio was further associated with low eosinophil levels and a low NLR before treatment initiation. Conclusions: These findings suggest a novel, easily obtainable blood-based signature that may help predict response to ICIs in ES-SCLC patients. Full article
(This article belongs to the Special Issue Immune Biomarkers in Solid Tumors: From Peripheral Blood Parameters to Tissue-Based Indicators for Prognosis and Therapy Response)
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11 pages, 1048 KB  
Article
Effect of Preoperative Sarcopenic Obesity on Outcomes in Patients with Gastric Cancer After Surgery
by Itaru Hashimoto, Keisuke Komori, Norihiro Akimoto, Yuta Nakayama, Shinsuke Nagasawa, Yukio Maezawa, Kyohei Kanematsu, Takanobu Yamada, Norio Yukawa, Aya Saito, Takashi Ogata and Takashi Oshima
Cancers 2026, 18(2), 191; https://doi.org/10.3390/cancers18020191 - 7 Jan 2026
Abstract
Background/Objectives: Preoperative body composition has been implicated as a factor affecting clinical outcomes in several types of cancer. However, there is limited evidence regarding whether preoperative body composition can predict the prognosis following gastrectomy for gastric cancer (GC). We aimed to investigate the [...] Read more.
Background/Objectives: Preoperative body composition has been implicated as a factor affecting clinical outcomes in several types of cancer. However, there is limited evidence regarding whether preoperative body composition can predict the prognosis following gastrectomy for gastric cancer (GC). We aimed to investigate the role of preoperative body composition as a prognostic factor for overall survival (OS) and relapse-free survival (RFS) after gastrectomy for GC. Methods: This prospective study included 540 patients who underwent gastrectomy for GC at the Kanagawa Cancer Center, Japan, between December 2013 and November 2017. Preoperative body composition was assessed using the skeletal muscle index and visceral adipose tissue area derived from computed tomography scans. Patients were classified into four groups: non-sarcopenic non-obesity (NN), sarcopenic non-obesity (SN), non-sarcopenic obesity (NO), and sarcopenic obesity (SO). Results: A total of 448 patients (NN, 184; SN, 52; NO, 186; SO, 26) were included in the final analysis. In terms of OS, the SO group showed significantly worse survival than the NN group (72.1% vs. 87.6%, p = 0.01). Similarly, regarding RFS, the SO group had significantly worse outcomes than the NN group (68.4% vs. 86.2%, p = 0.007). Multivariate analysis identified SO as an independent risk factor for both OS (hazard ratio [HR], 3.18; 95% confidence interval [CI], 1.33–7.64; p = 0.01) and RFS (HR, 3.08; 95% CI, 1.36–6.95; p = 0.01). Conclusions: Preoperative SO was associated with poorer outcomes in patients undergoing gastrectomy for GC. Full article
(This article belongs to the Special Issue Clinical Outcomes in Upper GI Cancers)
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14 pages, 588 KB  
Systematic Review
Application of Transthoracic and Endobronchial Elastography—A Systematic Review
by Christian Kildegaard, Rune W. Nielsen, Christian B. Laursen, Ariella Denize Nielsen, Amanda D. Juul, Tai Joon An, Dinesh Addala and Casper Falster
Cancers 2026, 18(2), 190; https://doi.org/10.3390/cancers18020190 - 7 Jan 2026
Abstract
Introduction: Ultrasound elastography is increasingly used across medical imaging, yet its role in thoracic disease remains poorly defined. While both transthoracic ultrasonography (TUS) and endobronchial ultrasound (EBUS) offer real-time assessment of pleural and pulmonary structures, the diagnostic and clinical value of elastography in [...] Read more.
Introduction: Ultrasound elastography is increasingly used across medical imaging, yet its role in thoracic disease remains poorly defined. While both transthoracic ultrasonography (TUS) and endobronchial ultrasound (EBUS) offer real-time assessment of pleural and pulmonary structures, the diagnostic and clinical value of elastography in this context remains uncertain. Materials and Method: A systematic search of MEDLINE, EMBASE, and the Cochrane Library was conducted according to PRISMA guidelines (April 2023; updated January 2025). Original studies evaluating transthoracic or endobronchial elastography for pleural or pulmonary conditions were included. Data extraction and quality assessment were performed independently by three reviewers, with QUADAS-2 used to evaluate risk of bias. Results: Thirty studies met inclusion criteria. Twenty-eight evaluated TUS elastography and two examined EBUS. Shear wave elastography was most frequently applied, particularly for differentiating malignant from benign pleural effusion or subpleural lesions. Surface wave elastography demonstrated consistently higher stiffness values in patients with interstitial lung disease compared with healthy controls, correlating with radiological and functional disease severity. Elastography-guided pleural biopsy improved diagnostic yield compared with conventional ultrasound-guided biopsy. Overall, substantial methodological variation existed among scanning techniques, elastography modalities, reporting methods, and diagnostic thresholds, limiting cross-study comparison. Conclusions: Ultrasound elastography shows promise for evaluating pleural effusion and pulmonary lesions, procedural guidance, and interstitial lung disease possibly improving diagnostic possibilities with bedside evaluation and reducing patient exposure to radiation. However, methodological variation and limited high-quality evidence preclude clinical implementation. Standardized acquisition protocols and multicentre validation studies are necessary to define its diagnostic utility in thoracic imaging. Full article
(This article belongs to the Special Issue Application of Ultrasound in Cancer Diagnosis and Treatment)
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14 pages, 604 KB  
Review
Oligometastatic Bladder Cancer: Current Definitions, Diagnostic Challenges, and Evolving Therapeutic Strategies
by Kieran Sandhu, David T. Hopkins, Matilda Newton, Niranjan Sathianathen, Sachin Perera, Nathan Lawrentschuk, Declan Murphy and Marlon Perera
Cancers 2026, 18(2), 189; https://doi.org/10.3390/cancers18020189 - 7 Jan 2026
Abstract
Background: Oligometastatic bladder cancer (OMBC) is increasingly recognised as an intermediate state between localised and widespread metastatic disease, although its definition and optimal management remain uncertain. Patients with OMBC have a generally more favourable prognosis compared to patients with metastatic disease. However, [...] Read more.
Background: Oligometastatic bladder cancer (OMBC) is increasingly recognised as an intermediate state between localised and widespread metastatic disease, although its definition and optimal management remain uncertain. Patients with OMBC have a generally more favourable prognosis compared to patients with metastatic disease. However, its definition, diagnostic criteria, and optimal management remain poorly standardised. Methods: This narrative review summarises current evidence on the definitions, diagnostic approaches, and treatment strategies for OMBC, with an emphasis on emerging biological and molecular insights that may refine disease classification and guide therapy. Results: Existing definitions of OMBC rely on lesion count and anatomical distribution, overlooking molecular and clinicopathological heterogeneity that influences prognosis and treatment response. Advances in Positron Emission Tomography (PET)/Computed Tomography (CT) and magnetic resonance imaging (MRI) have improved detection of small-volume disease, while liquid biopsy and circulating tumour DNA show promise for assessing micrometastatic burden. Therapeutic approaches, including metastasis-directed and consolidative therapies, are under investigation. Nonetheless, most data are derived from small, retrospective series, and evidence from prospective studies remains limited. Conclusions: Prospective, biomarker-integrated, and randomised trials are essential to refine definitions, optimise patient selection for therapy, and define the role of precision-based multimodal therapy in OMBC management. Full article
(This article belongs to the Special Issue Molecular and Clinical Challenges in Metastatic and Oligometastatic Genitourinary Cancers)
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11 pages, 1215 KB  
Article
Romiplostim for Prevention of Severe Chemotherapy-Induced Thrombocytopenia in Lymphoma Patients—Phase I Study
by Erel Joffe, Zachary Epstein-Peterson, Lorenzo Falchi, Ariela Noy, Andrew D. Zelenetz, Collette Owens, Leah Gilbert, Gilles Salles and Gerald A. Soff
Cancers 2026, 18(2), 188; https://doi.org/10.3390/cancers18020188 - 6 Jan 2026
Abstract
Background/Objectives: Intensive chemotherapy is the cornerstone of lymphoma treatment but often leads to severe chemotherapy-induced thrombocytopenia (sCIT), resulting in treatment delays, reduced dose intensity, and the need for transfusions. While granulocyte colony-stimulating factors (G-CSFs) are commonly used to manage neutropenia, the use of [...] Read more.
Background/Objectives: Intensive chemotherapy is the cornerstone of lymphoma treatment but often leads to severe chemotherapy-induced thrombocytopenia (sCIT), resulting in treatment delays, reduced dose intensity, and the need for transfusions. While granulocyte colony-stimulating factors (G-CSFs) are commonly used to manage neutropenia, the use of thrombopoietic growth factors has not been adequately studied. Methods: This phase I dose-finding study evaluated the use of weekly romiplostim as prophylaxis for recurrent sCIT in patients undergoing chemotherapy for lymphoma. Eligible patients were those treated with a 21-day chemotherapy cycle who previously experienced sCIT, thus serving as their own “controls”. sCIT was defined as one of the following: (A) a platelet count (PLT) <50 × 109/L on day 1 of the subsequent cycle, leading to delay or dose reduction in chemotherapy, or (B) grade 4 thrombocytopenia (<25 × 109/L) and/or (C) platelet transfusion for bleeding. The primary endpoints were the incidence of sCIT and the rate of romiplostim-associated-adverse-events, with thromboembolic complications being an event of special interest. Results: Nine patients with sCIT requiring a PLT transfusion on the prior treatment cycle were treated across three dose schedules. The phase 2 recommended schedule was defined as a starting dose of 3–5 mcg/kg based on the baseline PLT count, with weekly adjustments for counts <150 × 109/L and >450 × 109/L. Romiplostim prevented recurrent grade 4 thrombocytopenia in 47% of the chemotherapy cycles and averted recurrent transfusion in 65% of cycles. Notably, low starting doses, as used in solid malignancies, were insufficient, leading to recurrent thrombocytopenia. Conclusions: Romiplostim was well-tolerated, with no thromboembolic events, and allowed most patients to complete their chemotherapy on schedule at full dose intensity. Full article
(This article belongs to the Section Clinical Research of Cancer)
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12 pages, 1541 KB  
Article
Decoding Osteoradionecrosis of the Jaw: Radiological Progression and a Novel CT-Based Grading System
by Vasundhara Patil, Pritesh Shah, Abhishek Mahajan, Nilesh Sable, Anuradha Shukla, Gauri Bornak, Swapnil Rane, Sandeep Gurav, Sarbani Ghosh Laskar, Gouri Pantvaidya, Amit Janu, Suman Ankathi, Arpita Sahu, Kajari Bhattacharya, Nivedita Chakrabarty, Archi Agarwal, Prathamesh Pai, Deepa Nair, Anuja Deshmukh, Richa Vaish, Vidisha Tuljapurkar, Asawari Patil, Munita Bal, Kumar Prabhash, Vanita Noronha, Nandini Menon, Vijay Patil and Pankaj Chaturvediadd Show full author list remove Hide full author list
Cancers 2026, 18(2), 187; https://doi.org/10.3390/cancers18020187 - 6 Jan 2026
Abstract
Background: Osteoradionecrosis (ORN) of the jaw is a severe, progressive complication of radiation therapy for head and neck malignancies. ORN features radiologically overlaps osteomyelitis and tumor recurrence. This study analyzes jaw ORN imaging characteristics and progression and proposes an ORN CT-based grading [...] Read more.
Background: Osteoradionecrosis (ORN) of the jaw is a severe, progressive complication of radiation therapy for head and neck malignancies. ORN features radiologically overlaps osteomyelitis and tumor recurrence. This study analyzes jaw ORN imaging characteristics and progression and proposes an ORN CT-based grading system that builds on current ClinRAD grades. Materials and Methods: A retrospective cohort study of 35 patients with biopsy-proven or clinically diagnosed ORN following radiation therapy. Initial and follow-up imaging were assessed to evaluate the radiological evolution of ORN. The imaging findings were statistically analyzed using IBM SPSS v26, and literature comparisons were made. Results: The median onset of ORN post-radiotherapy was 27–28 months (range: 2–119 months). The most common clinical presentations included non-healing ulcers (49%), pain (34%), and discharging sinuses (31%). Mandibular involvement was predominant (51%), with focal bone alterations being more frequent (63%). CT findings at clinical suspicion of ORN included resorption (100%), erosions (100%), sclerosis (86%), and fragmentation (83%). Follow-up imaging showed increased bone erosion (77%), fragmentation (92%), and sclerosis (92%). A CT-based grading system is proposed to classify ORN progression. Conclusions: ORN follows a predictable radiological progression, beginning with trabecular resorption and cortical erosion, leading to fragmentation and sequestrum formation. The proposed grading system provides a structured approach for early diagnosis. The proposed grading system provides a structured approach for diagnosis. Larger studies of imaging analyses are required to validate these findings and refine diagnostic criteria. Full article
(This article belongs to the Special Issue The Development and Application of Imaging Biomarkers in Cancer)
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21 pages, 1666 KB  
Systematic Review
Radiomics for Predicting the Efficacy of Immunotherapy in Hepatocellular Carcinoma: A Systematic Review and Radiomics Quality Score Assessment
by Ruixin Zhang, Chengjie Zhang, Yi Liu, Zhiguo Gui and Anhong Zhang
Cancers 2026, 18(2), 186; https://doi.org/10.3390/cancers18020186 - 6 Jan 2026
Abstract
Background/Objectives: Hepatocellular carcinoma (HCC) immunotherapy provides limited clinical benefits, partly due to the lack of reliable efficacy biomarkers. Radiomics, which non-invasively analyzes tumor heterogeneity, shows promising potential for predicting treatment outcomes. Methods: The present study systematically evaluated the predictive performance and methodological quality [...] Read more.
Background/Objectives: Hepatocellular carcinoma (HCC) immunotherapy provides limited clinical benefits, partly due to the lack of reliable efficacy biomarkers. Radiomics, which non-invasively analyzes tumor heterogeneity, shows promising potential for predicting treatment outcomes. Methods: The present study systematically evaluated the predictive performance and methodological quality of radiomics models for assessing immunotherapy efficacy in patients with HCC. A literature search was conducted in PubMed, Web of Science, Embase, and the Cochrane Library for studies published up to 21 June 2025, which developed CT- or MRI-based radiomics models to predict immunotherapy efficacy in HCC. Study quality was assessed using the radiomics quality score (RQS) and the METhodological RadiomICs Score (METRICS). Results: A total of 11 studies were included and categorized by immunotherapy regimen: ICIs alone (1/11), ICIs combined with targeted therapy (6/11), and ICIs combined with targeted therapy plus locoregional therapy (4/11). The models primarily predicted treatment response (7/11), overall survival (OS) (4/11), or progression-free survival (PFS) (4/11). In the ICI monotherapy cohort, AUC values for predicting treatment response ranged from 0.705 to 0.772. In the ICI plus targeted therapy cohorts, AUC or concordance index (C-index) values for predicting the above efficacy endpoints were 0.792–0.956, 0.63–0.77, and 0.54–0.837, respectively. In the combination therapy cohorts incorporating locoregional treatment, predictive models showed AUC or C-index values of 0.721–0.92, 0.817–0.838, and 0.59. Quality assessment revealed a median RQS of 15 (range: 11–19) and a median METRICS of 72.5% (range: 56.0–79.5%) across all studies. Conclusions: CT/MRI-based radiomics uses routine imaging to non-invasively quantify whole-tumor phenotype and heterogeneity, enabling repeatable, longitudinal assessment in hepatocellular carcinoma. Evidence suggests that it can help to identify patients likely to benefit from immunotherapy before treatment. However, clinical implementation requires standardized imaging and analysis protocols, external validation, and transparent reporting. Full article
(This article belongs to the Section Systematic Review or Meta-Analysis in Cancer Research)
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54 pages, 3576 KB  
Review
Implementation of Natural Products and Derivatives in Acute Myeloid Leukemia Management: Current Treatments, Clinical Trials and Future Directions
by Faten Merhi, Daniel Dauzonne and Brigitte Bauvois
Cancers 2026, 18(2), 185; https://doi.org/10.3390/cancers18020185 - 6 Jan 2026
Abstract
Bioactive natural products (NPs) may play a critical role in cancer progression by targeting nucleic acids and a wide array of proteins, including enzymes. Furthermore, a large number of derivatives (NPDs), including semi-synthetic products and pharmacophores from NPs, have been developed to enhance [...] Read more.
Bioactive natural products (NPs) may play a critical role in cancer progression by targeting nucleic acids and a wide array of proteins, including enzymes. Furthermore, a large number of derivatives (NPDs), including semi-synthetic products and pharmacophores from NPs, have been developed to enhance the solubility and stability of NPs. Acute myeloid leukemia (AML) is a poor-prognosis hematologic malignancy characterized by the clonal accumulation in the blood and bone marrow of myeloid progenitors with high proliferative capacity, survival and propagation abilities. A number of potential pathways and targets have been identified for development in AML, and include, but are not limited to, Fms-like tyrosine kinase 3 (FLT3) and isocitrate dehydrogenases resulting from genetic mutations, BCL2 family members, various signaling kinases and histone deacetylases, as well as tumor-associated antigens (such as CD13, CD33, P-gp). By targeting nucleic acids, FLT3 or CD33, several FDA-approved NPs and NPDs (i.e., cytarabine, anthracyclines, midostaurin, melphalan and calicheamicin linked to anti-CD33) are the major agents of upfront treatment of AML. However, the effective treatment of the disease remains challenging, in part due to the heterogeneity of the disease but also to the involvement of the bone marrow microenvironment and the immune system in favoring leukemic stem cell persistence. This review summarizes the current state of the art, and provides a summary of selected NPs/NPDs which are either entering or have been investigated in preclinical and clinical trials, alone or in combination with current chemotherapy. With multifaceted actions, these biomolecules may target all hallmarks of AML, including multidrug resistance and deregulated metabolism. Full article
(This article belongs to the Special Issue Study on Acute Myeloid Leukemia)
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1 pages, 137 KB  
Correction
Correction: Sadagopan et al. Reduced Computed Tomography Scan Speed Improves Alignment Errors for Patients Undergoing Thoracic Stereotactic Body Radiation Therapy. Cancers 2025, 17, 2646
by Ramaswamy Sadagopan, Rachael M. Martin-Paulpeter, Christopher R. Peeler, Xiaochun Wang, Paige Nitsch and Julianne M. Pollard-Larkin
Cancers 2026, 18(2), 184; https://doi.org/10.3390/cancers18020184 - 6 Jan 2026
Abstract
In the original publication [...] Full article
(This article belongs to the Special Issue Stereotactic Body Radiation and Stereotactic Ablative Radiotherapy Therapy for Cancers 2nd edition)
15 pages, 1055 KB  
Article
Intraoperative Ex Vivo Shear-Wave Elastography of Sentinel Lymph Nodes in Endometrial Cancer and Other Gynaecological Malignancies
by Walid Shaalan, Mohamed Eldesouky, Theresa Mokry, Arved Bischoff, Peter Sinn, Nourhan Hassan, Riku Togawa, Dina Batarseh, Kathrin Haßdenteufel, Lara Meike Tretschock, Maryna Hlamazda, Christina Schmidt, Cecilie Torkildsen, Axel Gerhardt, Andre Hennigs, Lisa Katharina Nees, Oliver Zivanovic and Fabian Riedel
Cancers 2026, 18(2), 183; https://doi.org/10.3390/cancers18020183 - 6 Jan 2026
Abstract
Background: Accurate intraoperative assessment of sentinel lymph node (SLN) status is critical for staging and guiding surgical management in gynaecological malignancies. Frozen-section histopathology remains the gold standard, but it is time-consuming and resource-intensive. Shear-wave elastography (SWE) quantifies tissue stiffness in real time and [...] Read more.
Background: Accurate intraoperative assessment of sentinel lymph node (SLN) status is critical for staging and guiding surgical management in gynaecological malignancies. Frozen-section histopathology remains the gold standard, but it is time-consuming and resource-intensive. Shear-wave elastography (SWE) quantifies tissue stiffness in real time and may offer a rapid alternative. Methods: In this prospective single-centre study, 63 women (median age 62 years) undergoing primary surgery with sentinel lymph node biopsy (SLNB) for endometrial, cervical, vulvar, or early ovarian carcinoma were enrolled. A total of 172 SLNs were excised, submerged in coupling gel, and scanned ex vivo using a 9 MHz linear probe. Results: A total of 172 SLNs underwent SWE (mean 2.7 nodes/patient). Endometrial primaries accounted for 58% of nodes, mostly retrieved by robotic-assisted surgery (71.8%). Node dimensions were significantly larger in malignant lesions for sonographic (long-axis: 13.02 ± 3.31 mm vs. 10.80 ± 3.28 mm; p = 0.002) and pathological long-axis measurements (11.45 ± 2.83 mm vs. 9.75 ± 2.61 mm; p = 0.004). Mean SWE velocities were similar between groups (1.381 ± 0.307 vs. 1.343 ± 0.236 m/s; p = 0.541). Histopathology identified metastases in 18% of SLNs, comprising macrometastases (7%), micrometastases (5%), and isolated tumour cells (6%). Conclusions: Although ex vivo SWE is rapid, reproducible, and integrates seamlessly into the sterile field, stiffness measurements alone lack sufficient discriminatory power for SLN staging in gynaecological cancers. Future research should focus on three-dimensional SWE, advanced radiomic analyses, and machine-learning algorithms to improve the detection of low-volume metastatic disease. Full article
(This article belongs to the Special Issue Gynecologic Cancer: From Diagnosis to Treatment: 2nd Edition)
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26 pages, 856 KB  
Systematic Review
Intraperitoneal Chemotherapy Strategies in Pancreatic Ductal Adenocarcinoma: A Systematic Review of Hyperthermic Intraperitoneal Chemotherapy, Normothermic Intraperitoneal Chemotherapy, and Pressurized Intraperitoneal Aerosol Chemotherapy
by Nency Ganatra, Ahmed Abdelhakeem, Pragya Jain, Saivaishnavi Kamatham, Dina Elantably, Oluwatayo Adeoye, Hani M. Babiker, Conor D. O’Donnell and Umair Majeed
Cancers 2026, 18(2), 182; https://doi.org/10.3390/cancers18020182 - 6 Jan 2026
Abstract
Background: Peritoneal metastasis represents an aggressive disease pattern in pancreatic ductal adenocarcinoma (PDAC), traditionally associated with poor survival and limited therapeutic options. Emerging intraperitoneal chemotherapy strategies—including hyperthermic intraperitoneal chemotherapy (HIPEC), normothermic intraperitoneal paclitaxel (NIPEC/IP-PTX), and pressurized intraperitoneal aerosol chemotherapy (PIPAC)—have been investigated to [...] Read more.
Background: Peritoneal metastasis represents an aggressive disease pattern in pancreatic ductal adenocarcinoma (PDAC), traditionally associated with poor survival and limited therapeutic options. Emerging intraperitoneal chemotherapy strategies—including hyperthermic intraperitoneal chemotherapy (HIPEC), normothermic intraperitoneal paclitaxel (NIPEC/IP-PTX), and pressurized intraperitoneal aerosol chemotherapy (PIPAC)—have been investigated to improve local tumor control and survival outcomes. Methods: We systematically reviewed published studies evaluating HIPEC, NIPEC/IP-PTX, and PIPAC in PDAC, including adjuvant, cytoreductive, and palliative settings. Study characteristics, feasibility, perioperative outcomes, oncologic outcomes, and risk of bias were analyzed. Results: Across modalities, intraperitoneal treatment strategies demonstrated acceptable feasibility and safety profiles in appropriately selected patients. Adjuvant HIPEC following pancreatectomy showed reduced local–regional recurrence signals in limited cohorts. CRS + HIPEC among patients with isolated peritoneal metastases yielded encouraging multi-year survival in highly selected candidates achieving complete cytoreduction. NIPEC/IP-PTX demonstrated favorable ascites control, symptom relief, and potential conversion to resection in select patients. PIPAC was primarily used in unresectable, heavily pretreated, palliative peritoneal metastasis settings, with goals centered on disease stabilization, histologic regression, and symptom control rather than curative intent. Conclusions: Intraperitoneal chemotherapy strategies in PDAC appear feasible with signals of meaningful clinical benefit in select settings. While CRS + HIPEC may benefit carefully selected metastatic patients, NIPEC/IP-PTX and PIPAC hold value primarily in symptom control and disease stabilization. Larger prospective trials are needed to define patient selection, optimize treatment protocols, and clarify survival benefit. Full article
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Graphical abstract

16 pages, 533 KB  
Article
Molecular Classification and Clinical Outcomes in Endometrial Cancer: Real-World Evidence from a Tertiary Care Center
by Tanadon Salakphet, Prapaporn Suprasert, Tip Pongsuvareeyakul, Chinachote Teerapakpinyo and Surapan Khunamornpong
Cancers 2026, 18(2), 181; https://doi.org/10.3390/cancers18020181 - 6 Jan 2026
Abstract
Background: Molecular classification has reshaped prognostication and treatment in endometrial carcinoma (EC). However, real-world evidence from Asian populations remains scarce. This study evaluated clinicopathologic characteristics and survival outcomes across molecular subtypes of EC in a Thai tertiary care center. Methods: This retrospective cohort [...] Read more.
Background: Molecular classification has reshaped prognostication and treatment in endometrial carcinoma (EC). However, real-world evidence from Asian populations remains scarce. This study evaluated clinicopathologic characteristics and survival outcomes across molecular subtypes of EC in a Thai tertiary care center. Methods: This retrospective cohort included patients with histologically confirmed EC who underwent primary surgery at Chiang Mai University Hospital between 2015 and 2023, and had at least one investigation for molecular classification, including immunohistochemistry (IHC) for mismatch repair (MMR) proteins and p53, as well as POLE sequencing using the Idylla™ POLE–POLD1 Mutation Assay with confirmatory Sanger sequencing. Final molecular subtype assignment followed established hierarchical algorithms. Clinicopathologic variables were analyzed using Chi-square and logistic regression. Progression-free survival (PFS) and overall survival (OS) were estimated with Kaplan–Meier and compared using the log-rank test. Results: Among 803 EC cases diagnosed during the study period, 184 met the inclusion criteria. Of 184 patients, molecular subtypes were classified as POLE-mutated in 2.2%, dMMR in 38.6%, p53-abnormal (p53-abn) in 45.1% and NSMP (1.6%). dMMR tumors occurred predominantly in older women and exhibited mainly endometrioid histology, whereas p53-abn tumors were largely non-endometrioid and high-risk in the vast majority. In multivariate analysis, histologic type was the only independent predictor of both MMR deficiency (adjusted OR = 15.22; 95% CI 4.99–46.37; p < 0.001) and p53 abnormality (adjusted OR = 79.42; 95% CI 10.60–595.05; p = 0.003). Survival outcomes varied by molecular class: POLE-mutated tumors had excellent prognosis with no recurrence or death, dMMR tumors had intermediate outcomes, and p53-abn tumors showed the poorest PFS and OS. Overall survival differed significantly among subtypes. Conclusions: Molecular classification provides strong prognostic discrimination in EC, even with selective testing. MMR and p53 IHC serve as practical frontline tools, while POLE sequencing should be prioritized for intermediate- and high-risk endometrioid tumors. Expanded molecular testing in Asian populations is essential to refine risk stratification and optimize individualized management. Full article
(This article belongs to the Section Cancer Survivorship and Quality of Life)
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15 pages, 756 KB  
Article
Effect of Race and Tumor Subsite on Survival Outcome in Early- and Late-Onset Colorectal Cancer
by Mei-Chin Hsieh, Elena M. Stoffel, Kristen Purrington, Xiao-Cheng Wu, Jaeil Ahn, Siddhi Patil, Shengdi Wen, Muhammed Jawla, Batsirai Mabvakure and Laura S. Rozek
Cancers 2026, 18(2), 180; https://doi.org/10.3390/cancers18020180 - 6 Jan 2026
Abstract
Background: While colorectal cancer (CRC) incidence and mortality have declined among patients aged ≥50 years (late-onset), rates are increasing in those aged <50 years (early-onset). Historically, non-Hispanic Whites (NHW) have had better 5-year survival compared with non-Hispanic Blacks (NHB), and rectal cancer [...] Read more.
Background: While colorectal cancer (CRC) incidence and mortality have declined among patients aged ≥50 years (late-onset), rates are increasing in those aged <50 years (early-onset). Historically, non-Hispanic Whites (NHW) have had better 5-year survival compared with non-Hispanic Blacks (NHB), and rectal cancer has had better outcomes than colon cancer. Whether these disparities by race and tumor location are evident for both early-onset (EOCRC) and late-onset (LOCRC) CRC remains unclear. Methods: CRC cases diagnosed from 2011 to 2022 were identified from the Louisiana Tumor Registry. EOCRC was defined as diagnoses at ages 20–49 years, and LOCRC was defined as diagnoses at ages ≥50 years. Racial groups included NHW and NHB; tumor location was categorized as proximal colon, distal colon, or rectum. Cox regression was used to assess unadjusted and adjusted overall and cancer-specific survival. Results: Of 23,738 CRC patients, 10.7% were diagnosed at age <50 years. Compared to LOCRC, EOCRC patients included a higher proportion of NHB (37.5% vs. 32.6%) and rectal tumors (44.4% vs. 29.9%). NHB had worse overall survival than NHW in early-onset distal colon cancer (adjusted HR [aHR] = 1.358; 95%CI: 1.024–1.801). Conversely, NHB had better overall (aHR = 0.899; 95%CI: 0.831–0.973) and cancer-specific survival (aHR = 0.873; 95%CI: 0.793–0.960) in late-onset rectal cancer. Among EOCRC NHW, proximal tumors were associated with worse overall (aHR = 1.407; 95%CI: 1.102–1.796) and cancer-specific survival (aHR = 1.379; 95%CI: 1.057–1.799) compared with distal tumors. Conclusions: Survival differences by race and tumor subsite are observed between EOCRC and LOCRC, with NHB showing a lower hazard of death in some LOCRC subgroups. These findings highlight the need to consider the age of onset and tumor location when addressing racial disparities in CRC outcomes. Full article
(This article belongs to the Special Issue Emerging Trends in Global Cancer Epidemiology: 2nd Edition)
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13 pages, 1253 KB  
Article
Glucagon-like Peptide-1 Receptor Agonist Use and Pancreatic Cancer Risk in Patients with Chronic Pancreatitis
by Sarina Ailawadi, Jennifer E. Murphy, Michael H. Storandt and Amit Mahipal
Cancers 2026, 18(2), 179; https://doi.org/10.3390/cancers18020179 - 6 Jan 2026
Abstract
Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have advanced the treatment of type 2 diabetes mellitus (T2DM), yet their association with cancer risk remains subject of ongoing research. Chronic pancreatitis (CP) is a well-established risk factor for pancreatic cancer, yet the impact [...] Read more.
Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have advanced the treatment of type 2 diabetes mellitus (T2DM), yet their association with cancer risk remains subject of ongoing research. Chronic pancreatitis (CP) is a well-established risk factor for pancreatic cancer, yet the impact of GLP-1 RA therapy in this high-risk population is unknown. In this study, we aimed to evaluate the association between GLP-1 RA use and pancreatic cancer incidence among patients with CP, and among those with CP and T2DM. Methods: We performed a retrospective cohort study using data from TriNetX, a healthcare database of over 150 million patients in the United States. In the first analysis, adult patients with pre-existing CP were identified and stratified by use of a GLP-1 RA (semaglutide, dulaglutide, tirzepatide, exenatide, liraglutide, lixisenatide, and albiglutide). Propensity score matching (PSM) was conducted between GLP1-RA users and non-users, matching for age, sex, race, tobacco use, alcohol use, hypertension, hyperlipidemia, obesity, and pancreatic cysts. Five-year incidence of pancreatic cancer was compared between GLP-1 RA users and non-users in the matched cohort between 2015 and 2025. We then restricted the cohort to patients with CP and T2DM and repeated this analysis. Results: We identified 89,596 patients with CP, including 3183 GLP-1 RA users and 86,413 non-users. After PSM, GLP-1 RA use was associated with a lower 5-year incidence of pancreatic cancer (hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.30–0.80, p < 0.005). Similarly, amongst patients with CP and T2DM, GLP-1 RA use was associated with a lower 5-year incidence of pancreatic cancer (HR 0.53, 95% CI 0.31–0.91, p < 0.05). Conclusions: GLP-1 RA use was associated with a significantly reduced incidence of pancreatic cancer in all patients with CP, as well as the subpopulation with both CP and T2DM. Given the elevated cancer risk in CP, these findings suggest a potential beneficial effect of GLP-1RA use in this high-risk population. Prospective studies will be important to further analyze and confirm this potential benefit. Full article
(This article belongs to the Section Cancer Informatics and Big Data)
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