Cancers

11 pages, 2328 KiB

Open AccessArticle

Comparative Analysis of Repeatability in CT Radiomics and Dosiomics Features under Image Perturbation: A Study in Cervical Cancer Patients

by Zongrui Ma, Jiang Zhang, Xi Liu, Xinzhi Teng, Yu-Hua Huang, Xile Zhang, Jun Li, Yuxi Pan, Jiachen Sun, Yanjing Dong, Tian Li, Lawrence Wing Chi Chan, Amy Tien Yee Chang, Steven Wai Kwan Siu, Andy Lai-Yin Cheung, Ruijie Yang and Jing Cai

Cancers 2024, 16(16), 2872; https://doi.org/10.3390/cancers16162872 (registering DOI) - 18 Aug 2024

Abstract

This study aims to evaluate the repeatability of radiomics and dosiomics features via image perturbation of patients with cervical cancer. A total of 304 cervical cancer patients with planning CT images and dose maps were retrospectively included. Random translation, rotation, and contour randomization [...] Read more.

This study aims to evaluate the repeatability of radiomics and dosiomics features via image perturbation of patients with cervical cancer. A total of 304 cervical cancer patients with planning CT images and dose maps were retrospectively included. Random translation, rotation, and contour randomization were applied to CT images and dose maps before radiomics feature extraction. The repeatability of radiomics and dosiomics features was assessed using intra-class correlation of coefficient (ICC). Pearson correlation coefficient (r) was adopted to quantify the correlation between the image characteristics and feature repeatability. In general, the repeatability of dosiomics features was lower compared with CT radiomics features, especially after small-sigma Laplacian-of-Gaussian (LoG) and wavelet filtering. More repeatable features (ICC > 0.9) were observed when extracted from the original, Large-sigma LoG filtered, and LLL-/LLH-wavelet filtered images. Positive correlations were found between image entropy and high-repeatable feature number in both CT and dose (r = 0.56, 0.68). Radiomics features showed higher repeatability compared to dosiomics features. These findings highlight the potential of radiomics features for robust quantitative imaging analysis in cervical cancer patients, while suggesting the need for further refinement of dosiomics approaches to enhance their repeatability. Full article

(This article belongs to the Special Issue Radiomics and Imaging in Cancer Analysis)

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28 pages, 1533 KiB

Open AccessReview

Glutamine Metabolism and Prostate Cancer

by Holger H. H. Erb, Nikita Polishchuk, Oleh Stasyk, Uğur Kahya, Matthias M. Weigel and Anna Dubrovska

Cancers 2024, 16(16), 2871; https://doi.org/10.3390/cancers16162871 (registering DOI) - 18 Aug 2024

Abstract

Glutamine (Gln) is a non-essential amino acid that is involved in the development and progression of several malignancies, including prostate cancer (PCa). While Gln is non-essential for non-malignant prostate epithelial cells, PCa cells become highly dependent on an exogenous source of Gln. The [...] Read more.

Glutamine (Gln) is a non-essential amino acid that is involved in the development and progression of several malignancies, including prostate cancer (PCa). While Gln is non-essential for non-malignant prostate epithelial cells, PCa cells become highly dependent on an exogenous source of Gln. The Gln metabolism in PCa is tightly controlled by well-described oncogenes such as MYC, AR, and mTOR. These oncogenes contribute to therapy resistance and progression to the aggressive castration-resistant PCa. Inhibition of Gln catabolism impedes PCa growth, survival, and tumor-initiating potential while sensitizing the cells to radiotherapy. Therefore, given its significant role in tumor growth, targeting Gln metabolism is a promising approach for developing new therapeutic strategies. Ongoing clinical trials evaluate the safety and efficacy of Gln catabolism inhibitors in combination with conventional and targeted therapies in patients with various solid tumors, including PCa. Further understanding of how PCa cells metabolically interact with their microenvironment will facilitate the clinical translation of Gln inhibitors and help improve therapeutic outcomes. This review focuses on the role of Gln in PCa progression and therapy resistance and provides insights into current clinical trials. Full article

(This article belongs to the Special Issue Glutamine Metabolism in the Onset and Progression of Tumorigenesis)

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11 pages, 823 KiB

Open AccessPerspective

Challenges and Opportunities in Accessing Surgery for Glioblastoma in Low–Middle Income Countries: A Narrative Review

by Paolo Tini, Giovanni Rubino, Pierpaolo Pastina, Salvatore Chibbaro, Alfonso Cerase, Francesco Marampon, Sergio Paolini, Vincenzo Esposito and Giuseppe Minniti

Cancers 2024, 16(16), 2870; https://doi.org/10.3390/cancers16162870 (registering DOI) - 17 Aug 2024

Abstract

Glioblastoma: a highly aggressive brain tumor, presents substantial challenges in treatment and management, with surgical intervention playing a pivotal role in improving patient outcomes. Disparities in access to brain tumor surgery arise from a multitude of factors, including socioeconomic status, geographical location, and [...] Read more.

Glioblastoma: a highly aggressive brain tumor, presents substantial challenges in treatment and management, with surgical intervention playing a pivotal role in improving patient outcomes. Disparities in access to brain tumor surgery arise from a multitude of factors, including socioeconomic status, geographical location, and healthcare resource allocation. Low- and middle-income countries (LMICs) often face significant barriers to accessing surgical services, such as shortages of specialized neurosurgical expertise, limited healthcare infrastructure, and financial constraints. Consequently, glioblastoma patients in LMICs experience delays in diagnosis, suboptimal treatment, and poorer clinical outcomes compared to patients in high-income countries (HICs). The clinical impact of these disparities is profound. Patients in LMICs are more likely to be diagnosed at advanced disease stages, receive less effective treatment, and have lower survival rates than their counterparts in HICs. Additionally, disparities in access to surgical care exacerbate economic and societal burdens, emphasizing the urgent need for targeted interventions and health policy reforms to address healthcare inequities. This review highlights the importance of addressing global disparities in access to brain tumor surgery for glioblastoma through collaborative efforts, policy advocacy, and resource allocation, aiming to improve outcomes and promote equity in surgical care delivery for all glioblastoma patients worldwide. Full article

(This article belongs to the Special Issue Impact of Surgery on Brain Cancer and Other Central Nervous System Tumors)

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11 pages, 732 KiB

Open AccessArticle

Profiling the Cardiovascular Toxicities of CDK4/6 Inhibitors: A Real-World Pharmacovigilance Study

by Jae Hyun Kim

Cancers 2024, 16(16), 2869; https://doi.org/10.3390/cancers16162869 (registering DOI) - 17 Aug 2024

Abstract

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are approved for the treatment of human epidermal growth factor receptor 2 (HER-2)-negative, hormone receptor-positive breast cancer. The cardiovascular toxicity of CDK4/6 inhibitors is not well understood. This study aims to profile the cardiac events associated [...] Read more.

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are approved for the treatment of human epidermal growth factor receptor 2 (HER-2)-negative, hormone receptor-positive breast cancer. The cardiovascular toxicity of CDK4/6 inhibitors is not well understood. This study aims to profile the cardiac events associated with CDK4/6 inhibitors. Reports from 2015Q1 to 2024Q1 were obtained from the FDA Adverse Event Reporting System (FAERS). Reports identifying palbociclib, ribociclib, and abemaciclib as the primary suspect were examined for cardiovascular toxicity, including hypertension, cardiac failure, cardiomyopathy, arrhythmia, myocardial infarction, and myocarditis. Signal detection was performed using the proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC). A total of 69,139 reports were analyzed. The median time to adverse events was 69 days (interquartile range [IQR], 18–260 days). Of these, 2065 reports documented cardiac adverse events. Ribociclib and QT prolongation were re-confirmed as a signal (PRR 8.43, ROR 8.65, IC025 2.86). Hypertension and cardiac failure were the most frequently reported cardiovascular toxicities. This study demonstrates that the use of CDK4/6 inhibitors is associated with cardiovascular adverse events, such as heart failure and hypertension. Further research is needed to understand the mechanisms and risk factors contributing to the cardiovascular toxicity of CDK4/6 inhibitors. Full article

(This article belongs to the Special Issue Advances in Invasive Breast Cancer: Treatment and Prognosis)

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15 pages, 1494 KiB

Open AccessArticle

Molecular Analysis of Salivary and Lacrimal Adenoid Cystic Carcinoma

by Sarah Powell, Karina Kulakova, Katie Hanratty, Rizwana Khan, Paula Casserly, John Crown, Naomi Walsh and Susan Kennedy

Cancers 2024, 16(16), 2868; https://doi.org/10.3390/cancers16162868 (registering DOI) - 17 Aug 2024

Abstract

Adenoid cystic carcinoma (ACC) of head and neck origin is associated with slow but relentless progression and systemic metastasis, resulting in poor long-term survival rates. ACC does not respond to conventional chemotherapy. Determination of molecular drivers may provide a rational basis for personalized [...] Read more.

Adenoid cystic carcinoma (ACC) of head and neck origin is associated with slow but relentless progression and systemic metastasis, resulting in poor long-term survival rates. ACC does not respond to conventional chemotherapy. Determination of molecular drivers may provide a rational basis for personalized therapy. Herein, we investigate the clinical and detailed molecular genomic features of a cohort of patients treated in Ireland and correlate the site of origin, molecular features, and outcomes. Clinical and genomic landscapes of all patients diagnosed with ACC over a twenty-year period (2002–2022) in a single unit in Ireland were examined and analyzed using fluorescence in situ hybridization, DNA sequencing, and bioinformatic analysis. Fourteen patients were included for analysis. Eleven patients had primary salivary gland ACC and three primary lacrimal gland ACC; 76.9% of the analyzed tumors displayed evidence of NFIB-MYB rearrangement at the 6q23.3 locus; 35% had mutations in NOTCH pathway genes; 7% of patients had a NOTCH1 mutation, 14.3% NOTCH2 mutation, and 14.3% NOTCH3 mutation. The presence of epigenetic modifications in ACC patients significantly correlated with worse overall survival. Our study identifies genetic mutations and signaling pathways that drive ACC pathogenesis, representing potential molecular and therapeutic targets. Full article

(This article belongs to the Collection Application of Bioinformatics in Cancers)

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13 pages, 1288 KiB

Open AccessArticle

Risk and Protective Factors of Postoperative and Persistent Hypoparathyroidism after Total Thyroidectomy in a Series of 1965 Patients

by Silvia Dughiero, Francesca Torresan, Simona Censi, Caterina Mian, José Luis Carrillo Lizarazo and Maurizio Iacobone

Cancers 2024, 16(16), 2867; https://doi.org/10.3390/cancers16162867 (registering DOI) - 17 Aug 2024

Abstract

Background: Postoperative hypoparathyroidism (HypoPTH) is the most common complication following total thyroidectomy. Several risk factors have been identified, but data on postoperative follow-up are scarce. Methods: The study focused on 1965 patients undergoing surgery for benign and malignant thyroid diseases at a tertiary-level [...] Read more.

Background: Postoperative hypoparathyroidism (HypoPTH) is the most common complication following total thyroidectomy. Several risk factors have been identified, but data on postoperative follow-up are scarce. Methods: The study focused on 1965 patients undergoing surgery for benign and malignant thyroid diseases at a tertiary-level academic center. Anamnestic, biochemical, surgical, pathological, and follow-up data were evaluated. HypoPTH was defined by a serum concentration of PTH < 10 pg/mL on the first or the second post-operative day. Persistent HypoPTH was defined by the need for calcium/active vitamin D treatment > 12 months after surgery. Results: Postoperative HypoPTH occurred in 542 patients. Multivariate analysis identified the association of central lymph-nodal dissection, reduced preoperative PTH levels, a lower rate of parathyroid glands preserved in situ, and longer duration of surgery as independent risk factors. At a median follow-up of 47 months, HypoPTH regressed in 443 patients (more than 6 months after surgery in 7%) and persisted in 53 patients. Patients receiving a lower dose of calcium/active vitamin D treatment at discharge (HR 0.559; p < 0.001) or undergoing prolonged, tailored, and direct follow-up by the operating endocrine surgeon team had a significantly lower risk of persistent HypoPTH (2.4% compared to 32.8% for other specialists) (HR 2.563; p < 0.001). Conclusions: Various patient, disease, and surgeon-related risk factors may predict postoperative HypoPTH. Lower postoperative calcium/active vitamin D treatment and prolonged, tailored follow-up directly performed by operating endocrine surgeons may significantly reduce the rate of persistent HypoPTH. Full article

(This article belongs to the Special Issue New Insights into Thyroid Cancer Surgery)

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14 pages, 772 KiB

Open AccessReview

Cutaneous Squamous Cell Carcinoma of the Head and Neck: Pathological Features and What They Mean for Prognosis and Treatment

by Uma Ramesh, Elizabeth Chiang, Haleigh Stafford, Jane Buell, Frank Materia, Moran Amit and Dan Yaniv

Cancers 2024, 16(16), 2866; https://doi.org/10.3390/cancers16162866 (registering DOI) - 17 Aug 2024

Abstract

Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers worldwide, with an incidence that has increased over the past 30 years. Although usually curable with excision, cSCC can become widely metastatic and aggressive with poor outcomes. Whereas the clinical and [...] Read more.

Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers worldwide, with an incidence that has increased over the past 30 years. Although usually curable with excision, cSCC can become widely metastatic and aggressive with poor outcomes. Whereas the clinical and radiographic extent of any cancer will always guide selection of treatment modality, pathological features of cSCC also play an important role in determining prognosis and, subsequently, the need for further therapy. Therefore, reviewing and summarizing the current literature regarding pathological prognostic indicators of cSCC is essential to improving clinical outcomes. The present literature review yielded depth of invasion, surgical margins, perineural invasion, extranodal extension, lymphovascular invasion, tumor grade, tumor subtype, premalignant lesions, and molecular markers as key prognostic indicators, all with varying recommendations for adjuvant therapy. Notably, some of these factors have not been incorporated into either the American Joint Committee on Cancer staging system (8th edition) or National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology for cSCC. This review highlights a need for further research into these prognostic indicators and their role in determining the need for adjuvant treatment in head and neck cSCC. Full article

(This article belongs to the Section Cancer Immunology and Immunotherapy)

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24 pages, 1778 KiB

Open AccessReview

Current Knowledge and Perspectives of Immunotherapies for Neuroblastoma

by Chenkai Mao, Maria Poimenidou and Brian T. Craig

Cancers 2024, 16(16), 2865; https://doi.org/10.3390/cancers16162865 (registering DOI) - 17 Aug 2024

Abstract

Neuroblastoma (NBL) cells highly express disialoganglioside GD2, which is restricted and weakly expressed in selected healthy cells, making it a desirable target of immunotherapy. Over the past two decades, application of dinutuximab, an anti-GD2 monoclonal antibody (mAb), has been one of the few [...] Read more.

Neuroblastoma (NBL) cells highly express disialoganglioside GD2, which is restricted and weakly expressed in selected healthy cells, making it a desirable target of immunotherapy. Over the past two decades, application of dinutuximab, an anti-GD2 monoclonal antibody (mAb), has been one of the few new therapies to substantially improve outcomes to current levels. Given the persistent challenge of relapse and therapeutic resistance, there is an urgent need for new effective and tolerable treatment options for high-risk NBL. Recent breakthroughs in immune checkpoint inhibitor (ICI) therapeutics have not translated into high-risk NBL, like many other major pediatric solid tumors. Given the suppressed tumor microenvironment (TME), single ICIs like anti-CTLA4 and anti-PD1 have not demonstrated significant antitumor response rates. Meanwhile, emerging studies are reporting novel advancements in GD2-based therapies, targeted therapies, nanomedicines, and other immunotherapies such as adoptive transfer of natural killer (NK) cells and chimeric antigen receptors (CARs), and these hold interesting promise for the future of high-risk NBL patient care. Herein, we summarize the current state of the art in NBL therapeutic options and highlight the unique challenges posed by NBL that have limited the successful adoption of immune-modifying therapies. Through this review, we aim to direct the field’s attention to opportunities that may benefit from a combination immunotherapy strategy. Full article

(This article belongs to the Special Issue Combination Immunotherapy for Cancer Treatment)

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11 pages, 1531 KiB

Open AccessArticle

Real-Life Management of FLT3-Mutated AML: Single-Centre Experience over 24 Years

by Saveria Capria, Silvia Maria Trisolini, Lorenzo Torrieri, Elena Amabile, Giovanni Marsili, Alfonso Piciocchi, Walter Barberi, Anna Paola Iori, Daniela Diverio, Daniela Carmini, Massimo Breccia, Maurizio Martelli and Clara Minotti

Cancers 2024, 16(16), 2864; https://doi.org/10.3390/cancers16162864 (registering DOI) - 17 Aug 2024

Abstract

We analyzed 140 patients with a median age of 51 years; 21% had WBC ≥ 100 × 10⁹/L, and 52% had an NPM1 co-mutation. Until 2018, 101 patients received chemotherapy; thereafter, 39 received 3+7+midostaurin. The overall CR rate was 64%, higher [...] Read more.

We analyzed 140 patients with a median age of 51 years; 21% had WBC ≥ 100 × 10⁹/L, and 52% had an NPM1 co-mutation. Until 2018, 101 patients received chemotherapy; thereafter, 39 received 3+7+midostaurin. The overall CR rate was 64%, higher in NPM1 mutant patients (73%). Univariate analysis showed that NPM1 mutation (p = 0.032) and WBC < 100 × 10⁹/L (p = 0.013) positively influenced the response, with a trend for FLT3i administration (p = 0.052). Multivariate analysis confirmed WBC count as an independent prognostic factor (p = 0.017). In CR1, 41/90 patients underwent allogeneic and 18 autologous transplantation. The median EFS was 1.1 vs. 1.6 years in autografted and allografted patients, respectively (p = 0.9). The one-year non-relapse mortality was 0.00% for autologous and 28% for allogeneic transplants (p = 0.007); CIR at 1 and 3 years was higher in autologous transplants (39% vs. 15% and 57% vs. 21%, p = 0.004). The median survival was not reached in the FLT3i group. Overall, 69 patients received stem cell transplantation (18 autologous, 51 allogeneic). Post-transplant FLT3i was resumed in eight patients, all alive after a median of 65 months. Allogeneic transplantation is crucial in FLT3-mutated AML, but the next challenge will be to identify which patients can benefit from transplants in CR1 and in which to intensify post-transplant therapy. Full article

(This article belongs to the Special Issue Advances in Cancer Therapeutics)

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19 pages, 8018 KiB

Open AccessArticle

Morphological and Immunohistochemical Aspects with Prognostic Implications and Therapeutic Targets of Primary Sinonasal Mucosal Melanoma: A Retrospective Study

by Cornelia Marina Trandafir, Raluca Maria Closca, Marioara Poenaru, Oana Silvana Sarau, Cristian Andrei Sarau, Marina Rakitovan, Flavia Baderca and Laurentiu Vasile Sima

Cancers 2024, 16(16), 2863; https://doi.org/10.3390/cancers16162863 - 16 Aug 2024

Abstract

Sinonasal mucosal melanoma originates from melanocytes and it is a rare malignancy in the sinonasal tract. It is an aggressive melanocytic neoplasm with a very poor prognosis. The symptoms are nonspecific and the diagnosis is delayed, usually until the advanced stages of the [...] Read more.

Sinonasal mucosal melanoma originates from melanocytes and it is a rare malignancy in the sinonasal tract. It is an aggressive melanocytic neoplasm with a very poor prognosis. The symptoms are nonspecific and the diagnosis is delayed, usually until the advanced stages of the disease. The current study performs a correlation between the histopathological aspects of sinonasal mucosal melanoma and different types of immune cells present in the microenvironment, with prognostic and therapeutic implications. The endpoint is to quantify the cellular immune microenvironment and correlate it with patient survival. This study presents nine cases of primary sinonasal mucosal melanomas diagnosed at the Emergency City Hospital Timisoara, Romania during a period of 15 years. The histopathological examination was performed in the Department of Pathology of the same hospital, using morphological hematoxylin–eosin staining. Additional immunohistochemical reactions were performed to confirm the diagnosis and evaluate the components of the tumor immune microenvironment. This study identifies eosinophils, macrophages, natural killer cells and plasma cells as favorable prognostic factors. Therefore, a CD8:CD4 ratio of more than 3 is correlated with a good response to PD-1 inhibitor therapy. Full article

(This article belongs to the Special Issue Benign and Malignant Neoplasms of the Head and Neck)

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30 pages, 1495 KiB

Open AccessReview

Advances in Personalized Oncology

by Hiba Mechahougui, James Gutmans, Gina Colarusso, Roumaïssa Gouasmi and Alex Friedlaender

Cancers 2024, 16(16), 2862; https://doi.org/10.3390/cancers16162862 - 16 Aug 2024

Abstract

Advances in next-generation sequencing (NGS) have catalyzed a paradigm shift in cancer treatment, steering the focus from conventional, organ-specific protocols to precision medicine. Emerging targeted therapies offer a cutting-edge approach to cancer treatment, while companion diagnostics play an essential role in aligning therapeutic [...] Read more.

Advances in next-generation sequencing (NGS) have catalyzed a paradigm shift in cancer treatment, steering the focus from conventional, organ-specific protocols to precision medicine. Emerging targeted therapies offer a cutting-edge approach to cancer treatment, while companion diagnostics play an essential role in aligning therapeutic choices with specific molecular changes identified through NGS. Despite these advances, interpreting the clinical implications of a rapidly expanding catalog of genetic mutations remains a challenge. The selection of therapies in the presence of multiple mutations requires careful clinical judgment, supported by quality-centric genomic testing that emphasizes actionable mutations. Molecular tumor boards can play an increasing role in assimilating genomic data into clinical trials, thereby refining personalized treatment approaches and improving patient outcomes. Full article

(This article belongs to the Special Issue Pre-clinical Studies of Personalized Medicine for Cancer Research)

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36 pages, 1910 KiB

Open AccessReview

Unveiling the Dynamic Interplay between Cancer Stem Cells and the Tumor Microenvironment in Melanoma: Implications for Novel Therapeutic Strategies

by Patrizia Limonta, Raffaella Chiaramonte and Lavinia Casati

Cancers 2024, 16(16), 2861; https://doi.org/10.3390/cancers16162861 - 16 Aug 2024

Abstract

Cutaneous melanoma still represents a significant health burden worldwide, being responsible for the majority of skin cancer deaths. Key advances in therapeutic strategies have significantly improved patient outcomes; however, most patients experience drug resistance and tumor relapse. Cancer stem cells (CSCs) are a [...] Read more.

Cutaneous melanoma still represents a significant health burden worldwide, being responsible for the majority of skin cancer deaths. Key advances in therapeutic strategies have significantly improved patient outcomes; however, most patients experience drug resistance and tumor relapse. Cancer stem cells (CSCs) are a small subpopulation of cells in different tumors, including melanoma, endowed with distinctive capacities of self-renewal and differentiation into bulk tumor cells. Melanoma CSCs are characterized by the expression of specific biomarkers and intracellular pathways; moreover, they play a pivotal role in tumor onset, progression and drug resistance. In recent years, great efforts have been made to dissect the molecular mechanisms underlying the protumor activities of melanoma CSCs to provide the basis for novel CSC-targeted therapies. Herein, we highlight the intricate crosstalk between melanoma CSCs and bystander cells in the tumor microenvironment (TME), including immune cells, endothelial cells and cancer-associated fibroblasts (CAFs), and its role in melanoma progression. Specifically, we discuss the peculiar capacities of melanoma CSCs to escape the host immune surveillance, to recruit immunosuppressive cells and to educate immune cells toward an immunosuppressive and protumor phenotype. We also address currently investigated CSC-targeted strategies that could pave the way for new promising therapeutic approaches for melanoma care. Full article

(This article belongs to the Collection Deciphering the Crosstalk between Tumor Cells and Their Microenvironment: From Molecular Aspects to Therapeutic Implications)

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12 pages, 1632 KiB

Open AccessArticle

Molecular Diagnostic Yield and Safety Profile of Ultrasound-Guided Lung Biopsies: A Cross-Sectional Study

by Vito D’Agnano, Fabio Perrotta, Giulia Maria Stella, Raffaella Pagliaro, Filippo De Rosa, Francesco Saverio Cerqua, Angela Schiattarella, Edoardo Grella, Umberto Masi, Luigi Panico, Andrea Bianco and Carlo Iadevaia

Cancers 2024, 16(16), 2860; https://doi.org/10.3390/cancers16162860 - 16 Aug 2024

Abstract

Background: The recent advances in precision oncology for lung cancer treatment has focused attention on the importance of obtaining appropriate specimens for tissue diagnosis as well as comprehensive molecular profiling. CT scan-guided biopsies and bronchoscopy are currently the main procedures employed for tissue [...] Read more.

Background: The recent advances in precision oncology for lung cancer treatment has focused attention on the importance of obtaining appropriate specimens for tissue diagnosis as well as comprehensive molecular profiling. CT scan-guided biopsies and bronchoscopy are currently the main procedures employed for tissue sampling. However, growing evidence suggests that ultrasound-guided biopsies may represent an effective as well as safe approach in this diagnostic area. This study explores the safety and the diagnostic yield for cancer molecular profiling in ultrasound-guided percutaneous lung lesion biopsies (US-PLLB). Methods: One hundred consecutive patients with suspected lung cancer, between January 2021 and May 2024, who had ultrasound-guided lung biopsies have been retrospectively analyzed. Molecular profiling was conducted with next-generation sequencing Genexus using Oncomine precision assay or polymerase chain reaction according to specimen quality. Qualitative immunohistochemical assay of programmed death ligand 1 (PD-L1) expression was evaluated by the Dako PD-L1 immunohistochemistry 22C3 pharmDx assay. The co-primary endpoints were the molecular diagnostic yield and the safety profile of US-guided lung biopsies. Results: From January 2021 to May 2024, 100 US-guided lung biopsies were carried out and 95 were considered for inclusion in the study. US-PLLB provided informative tissue for a histological evaluation in 93 of 95 patients with an overall diagnostic accuracy of 96.84% [Sensitivity: 92.63%; Specificity: 96.84%; PPV: 100%; NPV: 100%]. Sixty-Six patients were diagnosed with NSCLC (69.47%) and were considered for molecular diagnostic yield evaluation and PD-L1 testing. Four patients had malignant lymphoid lesions. US-PLLB was not adequate to achieve a final diagnosis in three patients (3.16%). Complete molecular profiling and PD-L1 evaluation were achieved in all patients with adenocarcinoma (molecular diagnostic yield: 100%). PD-L1 evaluation was achieved in 28 of 29 patients (96.55%) with either SCC or NOS lung cancer. The overall complication rate was 9.47% (n = 9). Six patients (6.31%) developed pneumothorax, while three patients (3.16%) suffered mild haemoptysis without desaturation. Conclusions: According to our findings, US-guided lung biopsy is a safe, minimally invasive procedure in patients with suspected lung malignancies, providing an excellent diagnostic yield for both comprehensive molecular profiling and PD-L1 testing. In addition, our results suggest that US-guided biopsy may also be an effective diagnostic approach in patients with suspected lung lymphoma. Full article

(This article belongs to the Special Issue The Role of Radiotherapy, Immunotherapy and New Surgical Techniques in the Treatment of Lung Neoplasms)

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13 pages, 709 KiB

Open AccessArticle

Treosulfan-Versus Melphalan-Based Reduced Intensity Conditioning in HLA-Haploidentical Transplantation for Patients ≥ 50 Years With Advanced MDS/AML

by Alessia Fraccaroli, Elena Stauffer, Sarah Haebe, Dusan Prevalsek, Lena Weiss, Klara Dorman, Heidrun Drolle, Michael von Bergwelt-Baildon, Hans-Joachim Stemmler, Tobias Herold and Johanna Tischer

Cancers 2024, 16(16), 2859; https://doi.org/10.3390/cancers16162859 - 16 Aug 2024

Abstract

Relapse and regimen-related toxicities remain major challenges in achieving long-term survival, particularly among older patients with high-risk myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous studies have demonstrated the feasibility of treosulfan-based conditioning, noting stable [...] Read more.

Relapse and regimen-related toxicities remain major challenges in achieving long-term survival, particularly among older patients with high-risk myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous studies have demonstrated the feasibility of treosulfan-based conditioning, noting stable engraftment and low non-relapse mortality (NRM) in patients undergoing HLA-matched allo-HSCT. However, data on treosulfan-based conditioning in the HLA-haploidentical transplantation (HaploT) setting are limited. We retrospectively compared conditioning with fludarabine–cyclophosphamide (FC)–melphalan (110 mg/m²) and FC-treosulfan (30 g/m²) prior to HaploT using post-transplantation cyclophosphamide (PTCy) in patients with high-risk MDS/AML patients ≥ 50 years, transplanted from 2009–2021 at our institution (n = 80). After balancing patient characteristics by a matched-pair analysis, we identified twenty-one matched pairs. Two-year OS and LFS were similar among the groups (OS 66% and LFS 66%, p = 0.8 and p = 0.57). However, FC-melphalan was associated with a significantly lower probability of relapse compared to FC-treosulfan (0% vs. 24%, p = 0.006), counterbalanced by a higher NRM (33% vs. 10%, p = 0.05). Time to engraftment and incidences of acute and chronic graft-versus-host disease (GvHD) did not differ significantly. In conclusion, HaploT using FC-treosulfan in combination with PTCy in patients aged ≥50 years with MDS/AML appears safe and effective, particularly in advanced disease stages. We confirm the favorable extramedullary toxicity profile, allowing for potential dose intensification to enhance antileukemic activity. Full article

(This article belongs to the Collection Innovations in Cancer Drug Development Research)

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22 pages, 1700 KiB

Open AccessReview

Strategies for Improving CAR T Cell Persistence in Solid Tumors

by Megen C. Wittling, Anna C. Cole, Brianna Brammer, Kailey G. Diatikar, Nicole C. Schmitt and Chrystal M. Paulos

Cancers 2024, 16(16), 2858; https://doi.org/10.3390/cancers16162858 - 16 Aug 2024

Abstract

CAR T cells require optimization to be effective in patients with solid tumors. There are many barriers affecting their ability to succeed. One barrier is persistence, as to achieve an optimal antitumor response, infused CAR T cells must engraft and persist. This singular [...] Read more.

CAR T cells require optimization to be effective in patients with solid tumors. There are many barriers affecting their ability to succeed. One barrier is persistence, as to achieve an optimal antitumor response, infused CAR T cells must engraft and persist. This singular variable is impacted by a multitude of factors—the CAR T cell design, lymphodepletion regimen used, expansion method to generate the T cell product, and more. Additionally, external agents can be utilized to augment CAR T cells, such as the addition of novel cytokines, pharmaceutical drugs that bolster memory formation, or other agents during either the ex vivo expansion process or after CAR T cell infusion to support them in the oppressive tumor microenvironment. This review highlights many strategies being used to optimize T cell persistence as well as future directions for improving the persistence of infused cells. Full article

(This article belongs to the Special Issue CAR T Therapy of Solid Cancers: Problems and Progress)

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15 pages, 1063 KiB

Open AccessArticle

Predicting Postoperative Length of Stay in Patients Undergoing Laparoscopic Right Hemicolectomy for Colon Cancer: A Machine Learning Approach Using SICE (Società Italiana di Chirurgia Endoscopica) CoDIG Data

by Gabriele Anania, Matteo Chiozza, Emma Pedarzani, Giuseppe Resta, Alberto Campagnaro, Sabrina Pedon, Giorgia Valpiani, Gianfranco Silecchia, Pietro Mascagni, Diego Cuccurullo, Rossella Reddavid, Danila Azzolina and On behalf of SICE CoDIG (ColonDx Italian Group)

Cancers 2024, 16(16), 2857; https://doi.org/10.3390/cancers16162857 - 16 Aug 2024

Abstract

The evolution of laparoscopic right hemicolectomy, particularly with complete mesocolic excision (CME) and central vascular ligation (CVL), represents a significant advancement in colon cancer surgery. The CoDIG 1 and CoDIG 2 studies highlighted Italy’s progressive approach, providing useful findings for optimizing patient outcomes [...] Read more.

The evolution of laparoscopic right hemicolectomy, particularly with complete mesocolic excision (CME) and central vascular ligation (CVL), represents a significant advancement in colon cancer surgery. The CoDIG 1 and CoDIG 2 studies highlighted Italy’s progressive approach, providing useful findings for optimizing patient outcomes and procedural efficiency. Within this context, accurately predicting postoperative length of stay (LoS) is crucial for improving resource allocation and patient care, yet its determination through machine learning techniques (MLTs) remains underexplored. This study aimed to harness MLTs to forecast the LoS for patients undergoing right hemicolectomy for colon cancer, using data from the CoDIG 1 (1224 patients) and CoDIG 2 (788 patients) studies. Multiple MLT algorithms, including random forest (RF) and support vector machine (SVM), were trained to predict LoS, with CoDIG 1 data used for internal validation and CoDIG 2 data for external validation. The RF algorithm showed a strong internal validation performance, achieving the best performances and a 0.92 ROC in predicting long-term stays (more than 5 days). External validation using the SVM model demonstrated 75% ROC values. Factors such as fast-track protocols, anastomosis, and drainage emerged as key predictors of LoS. Integrating MLTs into predicting postoperative LOS in colon cancer surgery offers a promising avenue for personalized patient care and improved surgical management. Using intraoperative features in the algorithm enables the profiling of a patient’s stay based on the planned intervention. This issue is important for tailoring postoperative care to individual patients and for hospitals to effectively plan and manage long-term stays for more critical procedures. Full article

(This article belongs to the Special Issue Surgical Advances in Cancer Treatments: Exploring Innovative Approaches and Emerging Perspectives by the Italian College of Associate Professors of Surgery)

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15 pages, 2407 KiB

Open AccessArticle

Subxiphoid Single-Port Robotic Thymectomy Using the Single-Port Robotic System versus VATS: A Multi-Institutional, Retrospective, and Propensity Score-Matched Study

by Jun Hee Lee, Jinwook Hwang, Tae Hyun Park, Byung Mo Gu, Younggi Jung, Eunjue Yi, Sungho Lee, Soon Young Hwang, Jae ho Chung and Hyun Koo Kim

Cancers 2024, 16(16), 2856; https://doi.org/10.3390/cancers16162856 - 15 Aug 2024

Abstract

Subxiphoid thymectomy is a novel alternative to the transthoracic approach and sternotomy, with potential benefits, such as reduced postoperative pain and faster recovery. We previously reported the initial experience with subxiphoid single-port robotic-assisted thoracic surgery (SRATS) thymectomy using the single-port robotic system (SPS). [...] Read more.

Subxiphoid thymectomy is a novel alternative to the transthoracic approach and sternotomy, with potential benefits, such as reduced postoperative pain and faster recovery. We previously reported the initial experience with subxiphoid single-port robotic-assisted thoracic surgery (SRATS) thymectomy using the single-port robotic system (SPS). However, the efficacy of this technique remains unknown. Thus, this study examined the multi-institutional experience with SRATS thymectomy and compared the perioperative outcomes of this technique to those of subxiphoid single-port video-assisted thoracic surgery (SVATS) thymectomy. The data of patients who underwent subxiphoid SRATS and SVATS thymectomy, performed by three thoracic surgeons at three institutions between September 2018 and May 2024, were retrospectively collected. In total, 110 patients were included, with 85 and 25 undergoing SRATS and SVATS thymectomy, respectively. After propensity score matching, 25 patients were included in each group. The SRATS group was associated with a lower conversion rate to multi-port surgery (0% vs. 20%, p = 0.05), shorter chest tube drainage duration (1.32 ± 0.75 vs. 2.00 ± 1.29 days, p = 0.003), and a shorter postoperative hospital stay (2.52 ± 1.00 vs. 5.08 ± 5.20 days, p = 0.003). Subxiphoid SRATS thymectomy using the SPS is feasible and is a good alternative to conventional thymectomy. Further studies are necessary to confirm its benefits. Full article

(This article belongs to the Special Issue State of the Art: Cardiothoracic Tumors)

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12 pages, 1781 KiB

Open AccessArticle

Exploratory Study Identifies Matrix Metalloproteinase-14 and -9 as Potential Biomarkers of Regorafenib Efficacy in Metastatic Colorectal Cancer

by Mitsukuni Suenaga, Tetsuo Mashima, Naomi Kawata, Shingo Dan, Hiroyuki Seimiya and Kensei Yamaguchi

Cancers 2024, 16(16), 2855; https://doi.org/10.3390/cancers16162855 - 15 Aug 2024

Abstract

In identifying biomarkers for anticancer drugs, the lack of objectivity in selecting candidate factors makes interpretation difficult. We performed preclinical analysis and a translational validation study to identify candidate biomarkers for regorafenib efficacy in metastatic colorectal cancer (mCRC). Using in silico COMPARE analysis [...] Read more.

In identifying biomarkers for anticancer drugs, the lack of objectivity in selecting candidate factors makes interpretation difficult. We performed preclinical analysis and a translational validation study to identify candidate biomarkers for regorafenib efficacy in metastatic colorectal cancer (mCRC). Using in silico COMPARE analysis with a human cancer cell line panel, JFCR39, we selected candidate biomarkers whose expression correlates with regorafenib sensitivity. We validated predictive values in mCRC patients receiving regorafenib (discovery, n = 53) and FTD/TPI (control, n = 16). Blood samples were obtained at baseline (BL), before the second cycle (2nd), and at progressive disease (PD), and biomarker levels were measured using ELISA. Our analysis showed that high matrix metalloproteinase (MMP)-14 expression was associated with a high sensitivity to regorafenib. In the discovery cohort, high MMP-14 levels at BL and PD were correlated with tumor shrinkage and longer progression-free survival (PFS). A subsequent analysis of other related factors further indicated that the patients with decreased MMP-9 levels at the 2nd had higher disease control rates, tumor shrinkage, longer PFS, and overall survival than those with increased changes. These findings were not observed in the control cohort. Our study suggests MMP-14 and MMP-9 may serve as prognostic markers for regorafenib and provide insights into novel combination therapies with anti-MMP-9 agents or FTD/TPI. Full article

(This article belongs to the Special Issue Predictive Biomarkers for Colorectal Cancer)

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23 pages, 1005 KiB

Open AccessReview

Resistance to Anti-HER2 Therapies in Gastrointestinal Malignancies

by Christiana Mo, Michelle Sterpi, Hyein Jeon and Fernand Bteich

Cancers 2024, 16(16), 2854; https://doi.org/10.3390/cancers16162854 - 15 Aug 2024

Abstract

Human epidermal growth factor 2 (HER2) is a tyrosine kinase receptor that interacts with multiple signaling pathways related to cellular growth and proliferation. Overexpression or amplification of HER2 is linked to various malignancies, and there have been decades of research dedicated to targeting [...] Read more.

Human epidermal growth factor 2 (HER2) is a tyrosine kinase receptor that interacts with multiple signaling pathways related to cellular growth and proliferation. Overexpression or amplification of HER2 is linked to various malignancies, and there have been decades of research dedicated to targeting HER2. Despite the landmark ToGA trial, progress in HER2-positive gastrointestinal malignancies has been hampered by drug resistance. This review examines current HER2 expression patterns and therapies for gastroesophageal, colorectal, biliary tract, and small bowel cancers, while dissecting potential resistance mechanisms that limit treatment effectiveness. Full article

(This article belongs to the Section Cancer Drug Development)

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