Cancers

13 pages, 2097 KiB

Open AccessArticle

Risk of Postoperative Hemorrhage After Glioma Surgery in Patients with Preoperative Acetylsalicylic Acid

by Anatoli Pinchuk, Nikolay Tonchev, Claudia A. Dumitru, Belal Neyazi, Klaus-Peter Stein, I. Erol Sandalcioglu and Ali Rashidi

Cancers 2024, 16(22), 3845; https://doi.org/10.3390/cancers16223845 (registering DOI) - 15 Nov 2024

Abstract

Background/Objectives: Patients with gliomas show an increased risk of spontaneous hemorrhages throughout the disease. Simultaneously, the number of patients taking acetylsalicylic acid (ASA) for primary and secondary prophylaxis is rising in daily clinical practice, and interrupting ASA intake before elective or emergency intracranial [...] Read more.

Background/Objectives: Patients with gliomas show an increased risk of spontaneous hemorrhages throughout the disease. Simultaneously, the number of patients taking acetylsalicylic acid (ASA) for primary and secondary prophylaxis is rising in daily clinical practice, and interrupting ASA intake before elective or emergency intracranial surgery is not always feasible. This study aims to evaluate the risks associated with continuing ASA use perioperatively while focusing on hemorrhage and potential thromboembolic events that may arise from discontinuing ASA, particularly in multimorbid patients undergoing glioma surgery. Methods: The clinical parameters and imaging data of 7149 patients who underwent intracranial surgery in our department over a 10-year period were retrospectively analyzed. Patients were categorized into two groups based on their ASA status: Group 1 (no ASA impact) included those with no ASA use or who discontinued ASA use more than seven days prior to surgery (low stroke or cardiovascular risk), and Group 2 (ASA impact) included those who continued ASA use within seven days prior to operation (high stroke or cardiovascular risk). Results: In this retrospective study, data from 650 patients with various types of glial tumors who underwent surgery between 2008 and 2018 were examined. Of these patients, 50 experienced a postoperative hemorrhage (POH), and 10 required reoperations due to clinical neurological deterioration and increased intracranial pressure caused by the space-occupying effect of the hemorrhage. In the ASA impact group, 2.7% developed POH, compared to 1.3% in the no ASA impact group (p = 0.098). Our analysis did not show a significantly increased risk of POH after surgery, although patients in the ASA impact group had a one- to two-fold higher risk of developing POH overall. Additionally, other factors contributing to postoperative hemorrhage following glioma surgery were investigated and evaluated. Conclusions: In this cohort, the perioperative use of ASA was not associated with an increased rate of hemorrhagic complications after intracranial glioma surgery, although a trend was observed. In patients with high stroke and cardiovascular risk, ASA can be continued during elective brain tumor surgery. Full article

(This article belongs to the Special Issue Neurosurgical Management of Gliomas)

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13 pages, 507 KiB

Open AccessArticle

Impact of MASLD on Portal Vein Thrombosis Following Hepatectomy for Liver Cancer

by Yoshito Wada, Koji Okuda, Shin Sasaki, Shigeo Shimose, Takamichi Nishida, Hisaaki Shimokobe, Yuichi Nagao, Takayuki Torigoe, Koji Hayashi, Hidetoshi Akashi, Satoshi Taniwaki and Tetsuo Imamura

Cancers 2024, 16(22), 3844; https://doi.org/10.3390/cancers16223844 (registering DOI) - 15 Nov 2024

Abstract

Background: Due to the increasing global prevalence of non-alcoholic fatty liver disease (NAFLD), which is closely linked to metabolic disorders, there has been a rise in the number of patients with NAFLD undergoing hepatectomy. The metabolic disorders, as well as NAFLD, increase [...] Read more.

Background: Due to the increasing global prevalence of non-alcoholic fatty liver disease (NAFLD), which is closely linked to metabolic disorders, there has been a rise in the number of patients with NAFLD undergoing hepatectomy. The metabolic disorders, as well as NAFLD, increase venous thrombotic risk. NAFLD was recently updated to a new concept of hepatic steatosis: metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to investigate the impact of MASLD on post-hepatectomy portal vein thrombosis (PH-PVT). Methods: A total of 106 patients who underwent hepatectomy for liver cancer were included. Steatotic liver disease (SLD) was diagnosed using a CT L/S ratio of <1.1. SLD was classified as follows: MASLD, SLD associated with metabolic factors without alcohol consumption; MetALD, SLD with metabolic factors and moderate alcohol consumption; Other SLD, alcohol or other specific etiology of SLD; and No SLD, no hepatic steatosis. Results: PH-PVT was detected in 12/106 patients (11.3%); MASLD, 7/20 (35%); MetALD, 1/5 (20%); Other SLD, 1/13 (8%); and No SLD, 3/68 (4.4%). Multivariate analysis showed that the MASLD group (including MASLD and MetALD) (odds ratio [OR], 9.27) and left lateral sectionectomy (OR, 6.22) were significant independent risk factors for PH-PVT. Additionally, the incidence of PH-PVT was significantly higher in patients with MASLD than in those without SLD, along with metabolic factors, excluding alcohol consumption. Conclusions: MASLD and MetALD were identified as independent and significant risk factors for PH-PVT. Consideration was given to the idea that hepatic steatosis and metabolic dysfunction play synergistic roles in PH-PVT development. Full article

(This article belongs to the Special Issue Clinical Surgery for Hepato-Pancreato-Biliary (HPB) Cancer)

11 pages, 1083 KiB

Open AccessArticle

PSMA-Guided Imaging and Therapy of Advanced Adenoid Cystic Carcinomas and Other Salivary Gland Carcinomas

by Nils F. Trautwein, Andreas Brendlin, Gerald Reischl, Moritz Mattke, Frank Paulsen, Hubert Loewenheim, Lars Zender, Christian la Fougère and Helmut Dittmann

Cancers 2024, 16(22), 3843; https://doi.org/10.3390/cancers16223843 (registering DOI) - 15 Nov 2024

Abstract

SGCs are rare malignancies, accounting for less than 1% of all head and neck cancers [...] Full article

(This article belongs to the Special Issue Radioligand Therapy in Cancer)

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26 pages, 8277 KiB

Open AccessArticle

by Teodora G. Georgieva, Dalila Darmoul, Hwudaurw Chen, Haiyan Cui, Photini F. S. Rice, Jennifer K. Barton, David G. Besselsen and Natalia A. Ignatenko

Cancers 2024, 16(22), 3842; https://doi.org/10.3390/cancers16223842 (registering DOI) - 15 Nov 2024

Abstract

Background/Objectives: The objective of this study was to assess the role of a secreted serine protease, kallikrein-related peptidase 6 (KLK6), during colorectal tumorigenesis driven by a mutant Adenomatous polyposis coli (APC) tumor suppressor gene. A first analysis of KLK6 expression in the intestinal [...] Read more.

Background/Objectives: The objective of this study was to assess the role of a secreted serine protease, kallikrein-related peptidase 6 (KLK6), during colorectal tumorigenesis driven by a mutant Adenomatous polyposis coli (APC) tumor suppressor gene. A first analysis of KLK6 expression in the intestinal tract of Apc-mutant multiple intestinal neoplasia (Apc^Min/+) mice revealed up to four-fold induction of Klk6 mRNA levels in adenomas relative to its level in the adjacent mucosa. Methods and Results: The presence of KLK6 protein in the adenomatous areas was confirmed by immunohistochemistry and optical coherence tomography/laser-induced fluorescence (OCT/LIF) imaging. To assess the contribution of the KLK6 expression on the Apc-mutant intestinal and colon tumorigenesis, we engineered a mouse with floxed alleles of the Klk6 gene (Klk6^lox/lox) and crossed it with a mouse expressing the truncated APC protein under control of the intestinal tract-specific human CDX2P9.5-NLS Cre transgene (CPC;Apc^fl/fl;Klk6^+/+). We found that CPC;Apc^fl/fl mice with disrupted Klk6 gene expression (CPC;Apc^fl/fl;Klk6^fl/fl) had a significantly smaller average size of the small intestinal and colon crypts (p < 0.001 and p = 0.04, respectively) and developed a significantly fewer adenomas (p = 0.01). Moreover, a decrease in high-grade adenomas (p = 0.03) and adenomas with a diameter above 2 mm (p < 0.0001) was noted in CPC;Apc^fl/fl;Klk6^fl/fl mice. Further molecular analysis showed that Klk6 gene inactivation in the small intestine and colon tissues of CPC;Apc^fl/fl;Klk6^fl/fl mice resulted in a significant suppression of transforming growth factor β2 (TGF-β2) protein (p ≤ 0.02) and mitogen-activated protein kinase (MAPK) phosphorylation (p ≤ 0.01). Conclusions: These findings demonstrate the oncogenic role of KLK6 in the mutant Apc-mediated intestinal tumorigenesis and suggest the utility of KLK6 for early diagnosis of colorectal tumors. Full article

(This article belongs to the Section Cancer Biomarkers)

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27 pages, 9590 KiB

Open AccessReview

Posterior Retroperitoneal Laparoscopic Adrenalectomy: An Anatomical Essay and Surgical Update

by Bogdan Ovidiu Feciche, Vlad Barbos, Alexandru Big, Daniel Porav-Hodade, Alin Adrian Cumpanas, Silviu Constantin Latcu, Flavia Zara, Alina Cristina Barb, Cristina-Stefania Dumitru, Talida Georgiana Cut, Hossam Ismail and Dorin Novacescu

Cancers 2024, 16(22), 3841; https://doi.org/10.3390/cancers16223841 - 15 Nov 2024

Abstract

Posterior retroperitoneal laparoscopic adrenalectomy (PRLA) has emerged as a revolutionary, minimally invasive technique for adrenal gland surgery, offering significant advantages over traditional open approaches. This narrative review aims to provide a comprehensive update on PRLA, focusing on its anatomical foundations, surgical technique, and [...] Read more.

Posterior retroperitoneal laparoscopic adrenalectomy (PRLA) has emerged as a revolutionary, minimally invasive technique for adrenal gland surgery, offering significant advantages over traditional open approaches. This narrative review aims to provide a comprehensive update on PRLA, focusing on its anatomical foundations, surgical technique, and clinical implications. We conducted an extensive review of the current literature and surgical practices to elucidate the key aspects of PRLA. The procedure leverages a unique “backdoor” approach, accessing the adrenal glands through the retroperitoneum, which necessitates a thorough understanding of the posterior abdominal wall and retroperitoneal anatomy. Proper patient selection, meticulous surgical planning, and adherence to key technical principles are paramount for successful outcomes. In this paper, the surgical technique is described step by step, emphasizing critical aspects such as patient positioning, trocar placement, and adrenal dissection. PRLA demonstrates reduced postoperative pain, shorter hospital stays, and faster recovery times compared to open surgery, while maintaining comparable oncological outcomes for appropriately selected cases. However, the technique presents unique challenges, including a confined working space and the need for surgeons to adapt to a posterior anatomical perspective. We conclude that PRLA, in the right clinical setting, offers a safe and effective alternative to traditional adrenalectomy approaches. Future research should focus on expanding indications and refining techniques to further improve patient outcomes. Full article

(This article belongs to the Special Issue Urologic Cancer: Endoscopic, Laparoscopic, and Robot-Assisted Surgery Management)

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10 pages, 3944 KiB

Open AccessCommunication

Carcinoma-Associated Fibroblasts Accelerate Growth and Invasiveness of Breast Cancer Cells in 3D Long-Term Breast Cancer Models

by Kingsley O. Osuala, Joshua Heyza, Zhiguo Zhao, Yong Xu, Kamiar Moin, Kyungmin Ji and Raymond R. Mattingly

Cancers 2024, 16(22), 3840; https://doi.org/10.3390/cancers16223840 - 15 Nov 2024

Abstract

Background/Objectives: Carcinoma-associated fibroblasts (CAFs), a prominent cell type in the tumor microenvironment (TME), significantly contributes to cancer progression through interactions with cancer cells and other TME components. Consequently, targeting signaling pathways driven by CAFs has potential to yield new therapeutic approaches to inhibit [...] Read more.

Background/Objectives: Carcinoma-associated fibroblasts (CAFs), a prominent cell type in the tumor microenvironment (TME), significantly contributes to cancer progression through interactions with cancer cells and other TME components. Consequently, targeting signaling pathways driven by CAFs has potential to yield new therapeutic approaches to inhibit cancer progression. However, the mechanisms underlying their long-term interactions with cancer cells in vivo remains poorly understood. Methods: To address this, we developed a three-dimensional (3D) parallel coculture model of human triple-negative breast cancer (TNBC) cells and CAFs using our innovative TAME devices. This model allowed for the analysis of TNBC paracrine interactions via their secretome over extended culture periods (at least 70 days). Results: Using TNBC cell lines (MDA-MB-231, MCF10.DCIS, and HCC70), we found that TNBC spheroids in 3D parallel cocultures with CAFs exhibited more pronounced invasive finger-like outgrowths than those in cocultures of TNBC cells and normal fibroblasts (NFs) over a period of 50–70 days. We also established that the CAF-derived secretome affects TNBC migration towards the CAF secretome region. Additionally, we observed a preferential migration of CAFs, but not NFs, toward TNBC spheroids. Conclusions: Overall, our results suggest that paracrine interactions between TNBC cells and CAFs enhance TNBC invasive phenotypes and promote reciprocal migration. Full article

(This article belongs to the Special Issue Tumor Microenvironment of Breast Cancer)

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11 pages, 2287 KiB

Open AccessArticle

Survival Benefit of Primary Tumor Treatment in Uveal Melanoma: A Re-Analysis of the Collaborative Ocular Melanoma Study (COMS) and Natural History Study (NHS) Cohorts

by Hans Witzenhausen and Gustav Stalhammar

Cancers 2024, 16(22), 3839; https://doi.org/10.3390/cancers16223839 - 15 Nov 2024

Abstract

Objective: To evaluate whether primary tumor treatment provides a survival benefit in uveal melanoma by comparing patients who declined treatment (Natural History Study, NHS) with those who received treatment in the Collaborative Ocular Melanoma Study (COMS) for medium-sized choroidal melanomas. Methods: Individual-level survival [...] Read more.

Objective: To evaluate whether primary tumor treatment provides a survival benefit in uveal melanoma by comparing patients who declined treatment (Natural History Study, NHS) with those who received treatment in the Collaborative Ocular Melanoma Study (COMS) for medium-sized choroidal melanomas. Methods: Individual-level survival data were reverse-engineered from cumulative all-cause mortality curves in the original COMS and NHS publications. Censoring patterns were estimated from numbers at risk and descriptive statistics. A Bonferroni-corrected significance level of 0.017 was applied. Additionally, to ensure a conservative approach, NHS cohort data were iteratively adjusted by reducing the 8-year cumulative mortality by one percentage point if the Cox regression hazard ratio for all-cause mortality, the unadjusted risk ratio for death, and the 95% confidence intervals (CIs) of the Kaplan–Meier curves did not show a smaller survival difference than originally reported. Results: Kaplan–Meier analysis revealed significantly higher cumulative mortality in the NHS cohort compared to the COMS cohort (log–rank p = 0.012). When restricting the analysis to the first 8 years to account for unclear censoring patterns beyond this period, the NHS cohort still demonstrated worse survival (p = 0.008). A sensitivity analysis, varying censoring times by ±25% over 1000 iterations, confirmed worse survival in the NHS cohort in 100% of cases. Conclusions: In this re-evaluation, patients who declined treatment for medium-sized choroidal melanomas had significantly worse survival, suggesting a potential survival benefit of primary tumor treatment. Full article

(This article belongs to the Special Issue Advances in Uveal Melanoma)

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9 pages, 502 KiB

Open AccessArticle

Efficacy of Monopolar Radiofrequency or Microwave Ablation in Intrahepatic Cholangiocarcinoma: A Retrospective Multicenter Study from Association des Gastro-Entérologues Oncologues (AGEO)

by Antoine Briot, Germain Brehier, Anaïs Jaillais, Arthur David, Paul Girot, Noémi Reboux, Alice Boilève and Yann Touchefeu

Cancers 2024, 16(22), 3838; https://doi.org/10.3390/cancers16223838 - 15 Nov 2024

Abstract

Background: Several locoregional treatments approaches, including thermoablation, have been tested for the treatment of intrahepatic cholangiocarcinoma (ICC) and have shown encouraging results. However, data are heterogeneous in terms of tumor number, size, and ablation technique. Objective: The aim of this study was to [...] Read more.

Background: Several locoregional treatments approaches, including thermoablation, have been tested for the treatment of intrahepatic cholangiocarcinoma (ICC) and have shown encouraging results. However, data are heterogeneous in terms of tumor number, size, and ablation technique. Objective: The aim of this study was to investigate the efficacy and prognostic factors in ICC treated by monopolar radiofrequency (RF) or microwave ablation (MW). Methods: This was a retrospective study including patients treated with RF or MW for ICC in six participating centers. DFS and OS were evaluated by the Kaplan–Meier method and prognostic factors by log-rank test and Cox modeling. Results: From January 2015 to October 2023, 24 patients with 31 nodules were treated with RFA or MW. Overall, 70% had chronic liver disease, with 50% at cirrhosis stage. The median size of lesions was 17 mm (6–35 mm). After a median follow-up of 33 months (5–85), the median DFS was 10.5 months. The median OS was 40.8 months. On univariate and multivariate analysis, only lesion size > 17 mm was associated with a poor OS (HR 3.09; IC [1.02; 9.37] (p = 0.04). Conclusions: Monopolar radiofrequency or microwave ablation is an alternative to surgery for small ICCs. Tumors < 17 mm were associated with better OS. Full article

(This article belongs to the Section Cancer Therapy)

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12 pages, 729 KiB

Open AccessReview

Health Disparities and Inequities in the Utilization of Proton Therapy for Prostate Cancer

by Cyrus Gavin Washington and Curtiland Deville

Cancers 2024, 16(22), 3837; https://doi.org/10.3390/cancers16223837 - 15 Nov 2024

Abstract

Our study sought to review and summarize the reported health disparities and inequities in the utilization of proton beam therapy (PBT) for prostate cancer. We queried the PubMed search engine through 12/2023 for original publications examining disparate utilization of PBT for prostate cancer. [...] Read more.

Our study sought to review and summarize the reported health disparities and inequities in the utilization of proton beam therapy (PBT) for prostate cancer. We queried the PubMed search engine through 12/2023 for original publications examining disparate utilization of PBT for prostate cancer. The query terms included the following: prostate cancer AND proton AND (disparities OR IMRT OR race OR insurance OR socioeconomic OR inequities)”. Studies were included if they involved United States patients, examined PBT in prostate cancer, and addressed health inequities. From this query, 22 studies met the inclusion criteria, comprising 13 population-based analyses, 5 single-institutional analyses, 3 cost/modeling investigations, and 1 survey-based study. The analyses revealed that in addition to age-related and insurance-related disparities, race and socioeconomic status played significant roles in the receipt of PBT. The likelihood of receiving PBT was lower for non-White patients in population-based and single-institution analyses. Socioeconomic metrics, such as higher median income and higher education level, portended an increased likelihood of receiving PBT. Conclusively, substantial age-based, racial, socioeconomic/insurance-related, and facility-associated disparities and inequities existed for PBT utilization in prostate cancer. The identification of these disparities provides a framework to better address these as the utility of PBT continues to expand across the US and globally. Full article

(This article belongs to the Special Issue Advances of Particle Therapy in Prostate Cancer)

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15 pages, 9911 KiB

Open AccessArticle

Novel PP2A-Activating Compounds in Neuroblastoma

by Nazia Nazam, Laura V. Bownes, Janet R. Julson, Colin H. Quinn, Michael H. Erwin, Raoud Marayati, Hooper R. Markert, Sorina Shirley, Jerry E. Stewart, Karina J. Yoon, Jamie Aye, Michael Ohlmeyer and Elizabeth A. Beierle

Cancers 2024, 16(22), 3836; https://doi.org/10.3390/cancers16223836 - 15 Nov 2024

Abstract

Background: Neuroblastoma (NB) remains one of the deadliest pediatric solid tumors. Recent advancements aimed at improving outcomes have been insufficient, and patients with high-risk NB continue to have a poor prognosis. Protein phosphatase 2A (PP2A) is a tumor suppressor protein downregulated in many [...] Read more.

Background: Neuroblastoma (NB) remains one of the deadliest pediatric solid tumors. Recent advancements aimed at improving outcomes have been insufficient, and patients with high-risk NB continue to have a poor prognosis. Protein phosphatase 2A (PP2A) is a tumor suppressor protein downregulated in many cancers, including NB. PP2A activation has been shown to affect the malignant phenotype in other solid tumors. The present studies aim to investigate the effects of two novel PP2A activators as a NB therapeutic. Methods: Four established NB cell lines and a patient-derived xenoline were utilized to study the effect on cell viability, proliferation, motility, and in vivo tumor growth using two novel tricyclic sulfonamide PP2A activators, ATUX-3364 and ATUX-8385. Results: ATUX-3364 and ATUX-8385 increased PP2A activity. These PP2A activators led to decreased viability, proliferation, and motility of NB cells. Treatment of animals bearing NB tumors with ATUX-3364 or ATUX-8385 resulted in decreased tumor growth in MYCN-amplified SK-N-BE(2) tumors. At the molecular level, PP2A-based reactivation led to dephosphorylation of MYCN-S62 and decreased MYCN protein expression. Conclusions: PP2A activators decreased NB cell viability, proliferation, and motility. In vivo experiments show that PP2A activators have more significant effects on tumorigenesis in MYCN-amplified tumors. Finally, phosphorylation of MYCN protein was decreased following treatment with novel sulfonamide PP2A activators. These data and mechanistic insights may be useful for developing new PP2A-based therapies that target MYCN for the treatment of NB. Full article

(This article belongs to the Special Issue Pediatric Cancer Research from Basic Biology to Experimental Therapy)

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14 pages, 2130 KiB

Open AccessArticle

Real-World Outcomes of Selective RET Inhibitor Selpercatinib in the United States: Descriptive, Retrospective Findings from Two Databases

by Chi-Yin Liao, Carmen Gonzalez-Ferrer, Samuel Whipple, Patrick M. Peterson, Scott S. Barker, Naleen Raj Bhandari and Feng Wang

Cancers 2024, 16(22), 3835; https://doi.org/10.3390/cancers16223835 - 15 Nov 2024

Abstract

Objectives: This study described real-world patient characteristics and outcomes among selpercatinib-treated patients in the United States, using the Flatiron Health electronic health record-derived deidentified database (FHD) for advanced/metastatic non-small cell lung cancer (a/mNSCLC) and Optum’s de-identified Clinformatics^® Data Mart Database (CDM). Methods: [...] Read more.

Objectives: This study described real-world patient characteristics and outcomes among selpercatinib-treated patients in the United States, using the Flatiron Health electronic health record-derived deidentified database (FHD) for advanced/metastatic non-small cell lung cancer (a/mNSCLC) and Optum’s de-identified Clinformatics^® Data Mart Database (CDM). Methods: Patients initiating selpercatinib treatment between 08MAY2020 and 30JUN2023 were included. We evaluated real-world time to selpercatinib treatment discontinuation or death (rwTTDd) and time to next treatment or death (rwTTNTd) using Kaplan–Meier analyses. Medication possession ratio (MPR) was estimated as a measure of medication adherence in CDM patients. Results: In a/mNSCLC patients from the FHD (N = 68), the median rwTTDd and rwTTNTd were 22.4 [95%CI: 13.3–NR] and 21.0 [95%CI: 11.6–NR] months, respectively. In CDM, these durations were 12.1 [95%CI: 9.6–NR] and 16.2 [95%CI: 9.6–NR] months for lung cancer (n = 43), while these were not reached for thyroid cancer (n = 24) patients. The median MPR was 0.98 [IQR: 0.84–1.00] among all patients in the CDM (N = 75), with 77.3% of patients adhering (MPR ≥ 0.80) to selpercatinib. Conclusions: Real-world outcomes in this older and frailer patient cohort align with phase 3 trial results, further supporting selpercatinib as the standard of care for patients with RET-altered cancers. Early testing for the detection of RET alterations remains essential. Full article

(This article belongs to the Section Cancer Drug Development)

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7 pages, 595 KiB

Open AccessCommunication

On the Prognostic Implication of Delays in the Definitive Treatment of Uveal Melanoma

by Gustav Stålhammar, Salvatore Grisanti and Paul T. Finger

Cancers 2024, 16(22), 3834; https://doi.org/10.3390/cancers16223834 - 14 Nov 2024

Abstract

Background: Recent studies suggest that delays in the definitive treatment of uveal melanoma may increase the risk of metastatic disease. This topic has been the subject of considerable debate. Methods: In this study, we combine and contrast medical evidence from several recent publications [...] Read more.

Background: Recent studies suggest that delays in the definitive treatment of uveal melanoma may increase the risk of metastatic disease. This topic has been the subject of considerable debate. Methods: In this study, we combine and contrast medical evidence from several recent publications seeking to clarify the association between treatment delays and prognosis. Results: Emerging evidence indicates that metastatic seeding may continue until the primary tumor is effectively treated. Metastases that arise later in the disease course may carry additional genetic aberrations, enhancing their capacity to establish fatal macrometastases. Importantly, previous reports of shared mutations between primary tumors and metastases should not be interpreted as evidence that all metastases are seeded early. On the contrary, some tumors acquire additional driver mutations in the later stages, which are subsequently shared between the primary tumors and metastases. The increased risk of metastasis in patients with local tumor recurrence further highlights the importance of timely treatment. Additionally, new data on circulating tumor cells and treatment timing challenge the traditional practice of observing small melanomas. Conclusions: Observation is still warranted for indeterminate lesions to confirm malignancy. However, once a melanoma diagnosis has been established, further observation is harmful, and treatment should be administered as soon as reasonably possible. Full article

(This article belongs to the Special Issue Clinical Diagnosis, Treatment, and Prognosis of Uveal Melanoma)

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10 pages, 536 KiB

Open AccessArticle

Validation of the Scottish Inflammatory Prognostic Score (SIPS) in NSCLC Patients Treated with First-Line Pembrolizumab

by Igor Gomez-Randulfe, Fabio Gomes, Melanie MacKean, Iain Phillips and Mark Stares

Cancers 2024, 16(22), 3833; https://doi.org/10.3390/cancers16223833 - 14 Nov 2024

Abstract

Background: The Scottish Inflammatory Prognostic Score (SIPS), combining albumin (≥/<35 g/L) and neutrophil count (≤/>7.5 × 10⁹/L), has been identified as a prognostic biomarker for patients with non-small cell lung cancer (NSCLC) undergoing treatment with pembrolizumab monotherapy. We sought to validate [...] Read more.

Background: The Scottish Inflammatory Prognostic Score (SIPS), combining albumin (≥/<35 g/L) and neutrophil count (≤/>7.5 × 10⁹/L), has been identified as a prognostic biomarker for patients with non-small cell lung cancer (NSCLC) undergoing treatment with pembrolizumab monotherapy. We sought to validate this biomarker of systemic inflammation in an external cohort. Methods: Patients treated with first-line pembrolizumab for advanced NSCLC with programmed death-ligand 1 (PD-L1) expression ≥ 50% at an English cancer centre were identified. Pre-treatment clinicopathological characteristics and the SIPS were recorded. The relationship between these and progression-free survival (PFS) and overall survival (OS) was examined. Results: Among 257 patients evaluated, 56% (n = 144) were classified as SIPS 0, 36% (n = 93) as SIPS 1, and 8% (n = 20) as SIPS 2. Factors such as age, performance status (PS) and brain metastases presence were significantly correlated with SIPS categories. Multivariate analysis revealed that both SIPS and PD-L1 status were independently associated with PFS and OS. The combination of SIPS with either PS or PD-L1 expression enhanced the ability to detect patients with the most favourable or poorest survival. Conclusions: Our study confirms the prognostic significance of the SIPS in patients with advanced NSCLC treated with pembrolizumab in the context of high PD-L1 expression. SIPS offers a straightforward, clinically applicable approach to patient stratification, potentially guiding therapeutic decisions and enhancing outcomes in advanced NSCLC. Future research should focus on validating these findings in prospective studies and exploring the integration of SIPS into clinical practice, alongside other prognostic markers, to optimize treatment strategies. Full article

(This article belongs to the Special Issue Feature Papers in Section "Cancer Biomarkers" in 2023–2024)

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11 pages, 256 KiB

Open AccessReview

Do Patient-Reported Outcome Measures (PROMs) Used Within Radiotherapy Clinical Trials Reflect the Impact of Treatment?

by Danielle Fairweather, Rachel M. Taylor, Laura Allington, Nazima Haji, Naomi Fersht, Yen-Ching Chang and Rita Simões

Cancers 2024, 16(22), 3832; https://doi.org/10.3390/cancers16223832 - 14 Nov 2024

Abstract

This is the first article that investigates whether the patient-reported outcome measures (PROMs) used in clinical trials effectively capture the specific side-effects of radiotherapy and proton beam therapy (PBT) and provides context for researchers selecting PROMs for clinical trials. PROMs from radiotherapy trials [...] Read more.

This is the first article that investigates whether the patient-reported outcome measures (PROMs) used in clinical trials effectively capture the specific side-effects of radiotherapy and proton beam therapy (PBT) and provides context for researchers selecting PROMs for clinical trials. PROMs from radiotherapy trials were identified from previous research and assessed against the United Kingdom Royal College of Radiologists’ guidelines for tumour-site-specific side-effects. The analysis revealed that none of the 51 identified PROMs captured the full range of side-effects, with only 25 addressing fatigue and 6 addressing radiation-induced skin reactions. Three PROMs failed to identify any common side-effects, and eight identified only one. Overall, 88% of PROMs lacked specificity to radiotherapy and PBT, posing a risk of missing significant differences between treatment techniques. This study emphasises the need for more targeted PROMs in future trials. Until new or improved PROMs are available, great thought and caution should be taken when selecting PROMs for trial endpoints. Full article

(This article belongs to the Section Clinical Research of Cancer)

17 pages, 761 KiB

Open AccessReview

Exploring Carcinoid Syndrome in Neuroendocrine Tumors: Insights from a Multidisciplinary Narrative Review

by Matteo Marasco, Elena Romano, Giulia Arrivi, Daniela Prosperi, Maria Rinzivillo, Damiano Caruso, Paolo Mercantini, Michele Rossi, Antongiulio Faggiano and Francesco Panzuto

Cancers 2024, 16(22), 3831; https://doi.org/10.3390/cancers16223831 - 14 Nov 2024

Abstract

Carcinoid syndrome (CS) is a rare condition associated with neuroendocrine tumors (NETs), particularly those originating in the gastrointestinal tract, which secrete bioactive substances like serotonin. The management of CS requires a multidisciplinary approach due to its complex clinical manifestations, including flushing, diarrhea, bronchospasm, [...] Read more.

Carcinoid syndrome (CS) is a rare condition associated with neuroendocrine tumors (NETs), particularly those originating in the gastrointestinal tract, which secrete bioactive substances like serotonin. The management of CS requires a multidisciplinary approach due to its complex clinical manifestations, including flushing, diarrhea, bronchospasm, and carcinoid heart disease. Optimal care involves collaboration between several professional figures like oncologists, endocrinologists, gastroenterologists, surgeons, and dietitians. Currently, a wide range of treatments are available, focused on both symptom control and tumor burden reduction. Somatostatin analogs (SSAs) are the first-line therapy for symptom relief. Still, in patients with progressive disease or refractory CS, other options include targeted therapies, peptide receptor radionuclide therapy (PRRT), liver-directed therapies, and surgical resection, when feasible. Furthermore, management of complications related to prolonged serotonin release and malnutrition as a result of exocrine pancreatic insufficiency, post-surgical conditions, vitamin deficit, and chronic diarrhea often requires early detection to mitigate symptoms and improve the quality of life in these patients. The complexity of CS necessitates individualized care and continuous coordination among specialists to optimize outcomes and enhance patient well-being. Full article

(This article belongs to the Special Issue Neuroendocrine Tumors: From Diagnosis to Therapy)

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14 pages, 871 KiB

Open AccessArticle

Are All Prognostic Stage IB Breast Cancers Equivalent?

by Stephanie M. Yoon, Shengyang Wu, Amanda Schwer, Scott Glaser, Todd DeWees and Jose G. Bazan

Cancers 2024, 16(22), 3830; https://doi.org/10.3390/cancers16223830 - 14 Nov 2024

Abstract

Background/Objectives: The 8th edition of the American Joint Committee on Cancer integrates histology and biomarker status with anatomic extent in breast cancer (BC) pathologic prognostic staging (PPS). However, PPS IB includes anatomic locally advanced hormone-receptor-positive/HER2-negative (LA-HR+/HER2-) and early-stage triple-negative BC (ES-TNBC). Previous research [...] Read more.

Background/Objectives: The 8th edition of the American Joint Committee on Cancer integrates histology and biomarker status with anatomic extent in breast cancer (BC) pathologic prognostic staging (PPS). However, PPS IB includes anatomic locally advanced hormone-receptor-positive/HER2-negative (LA-HR+/HER2-) and early-stage triple-negative BC (ES-TNBC). Previous research shows that increased nodal involvement is a critical predictor of worse prognosis, raising questions about whether biological subtype or anatomic stage has a greater influence on outcomes in these discordant cases. We hypothesized that overall survival (OS) remains worse for LA-HR+/HER2- BC compared to ES-TNBC, despite both being classified as PPS IB. Methods: Using the National Cancer Database, we identified patients with LA-HR+/HER2- BC (pT3N1 or pT1-3N2, grade 1–2) and ES-TNBC (T1N0, grade 2–3) treated between 2004 and 2017. Patients without complete primary tumor stage, biomarker status, grade, TNM staging, or treated with neoadjuvant therapy were excluded. The primary endpoint was OS. Multivariable Cox regression evaluated OS between LA-HR+/HER2- BC and ES-TNBC. Results: Among 45,818 patients (17,359 LA-HR+/HER2- BC and 28,459 ES-TNBC), LA-HR+/HER2- BC had significantly worse 6-year OS (86.1% vs. 90.4%; HR = 1.63; p < 0.0001). Among patients receiving appropriate therapies, patients with LA-HR+/HER2- BC had 35% relatively higher risk of death (HR = 1.35; 1.24–1.48; p < 0.0001). These results highlight that LA-HR+/HER2- breast cancer has worse survival compared to ES-TNBC, despite both being classified as PPS IB and receiving all appropriate treatments. Conclusions: Anatomic disease extent remains an important factor in patients with discordant AS and PPS. Future iterations of PPS should re-classify LA-HR+/HER2- breast cancer from PPS IB to ensure more accurate prognostic and survival information. Full article

(This article belongs to the Special Issue Breast Cancer: Biomarkers of Diagnosis and Prognosis)

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13 pages, 439 KiB

Open AccessArticle

Impact of Screening on Mortality for Patients Diagnosed with Hepatocellular Carcinoma in a Safety-Net Healthcare System: An Opportunity for Addressing Disparities

by Kalyani Narra, Madison Hull, Kari J. Teigen, Vedaamrutha Reddy, Jolonda C. Bullock, Riyaz Basha, Nadia Alawi-Kakomanolis, David E. Gerber and Timothy J. Brown

Cancers 2024, 16(22), 3829; https://doi.org/10.3390/cancers16223829 - 14 Nov 2024

Abstract

Purpose: We describe the impact of screening on outcomes of patients diagnosed with hepatocellular carcinoma (HCC) in an urban safety-net healthcare system compared to a non-screened cohort diagnosed with HCC. Methods: Patients diagnosed with HCC at John Peter Smith Health Network were identified [...] Read more.

Purpose: We describe the impact of screening on outcomes of patients diagnosed with hepatocellular carcinoma (HCC) in an urban safety-net healthcare system compared to a non-screened cohort diagnosed with HCC. Methods: Patients diagnosed with HCC at John Peter Smith Health Network were identified by querying the hospital tumor registry and allocated to the screened cohort if they had undergone any liver imaging within one year prior to HCC diagnosis, while the remainder were allocated to the non-screened cohort. Kaplan–Meier methods and log-rank tests were used to compare 3-year survival curves from an index date of HCC diagnosis. Cox proportional hazard models were used to calculate unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). The Duffy adjustment was used to address lead-time bias. Results: A total of 158 patients were included (n = 53 screened, n = 105 non-screened). The median overall survival (OS) for the screened cohort was 19.0 months (95% CI: 9.9–NA) and that for the non-screened cohort was 5.4 months (95% CI: 3.7–8.5) [HR death (non-screened vs. screened) = 2.4, 95% CI: 1.6-3.6; log rank p < 0.0001]. The benefit of screening remained after adjusting for lead-time bias (HR 2.19, 95% CI 1.4–3.3, p = 0.0002). Conclusions: In an urban safety-net population, screening for HCC was associated with improved outcomes compared to patients diagnosed with HCC outside of a screening protocol. Full article

(This article belongs to the Special Issue Emerging Trends in Global Cancer Epidemiology: 2nd Edition)

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15 pages, 23685 KiB

Open AccessReview

External Hemipelvectomy in Soft Tissue Sarcomas: Are They Still Needed?

by Luis Rafael Ramos Pascua, Paula Casas Ramos, Lidia De la Cruz Gutiérrez, Maximiliano Eugenio Negri, Elena Vilar González, Julio César Córdova Peralta, María Inmaculada Mora Fernández and Jesús Enrique Vilá y Rico

Cancers 2024, 16(22), 3828; https://doi.org/10.3390/cancers16223828 - 14 Nov 2024

Abstract

Background: The development of new technologies, the interpretation of amputations as therapeutic failures by society, and the high morbidity and mortality associated with external hemipelvectomies make these mutilating surgical procedures appear obsolete. Herein, we review the scientific literature on the topic and present [...] Read more.

Background: The development of new technologies, the interpretation of amputations as therapeutic failures by society, and the high morbidity and mortality associated with external hemipelvectomies make these mutilating surgical procedures appear obsolete. Herein, we review the scientific literature on the topic and present two cases of high-grade ulcerated soft tissue sarcomas in the gluteal region which show exceptional behavior and different outcomes. Methods: We performed a literature review of the PubMed databases from 2014 to April 2024. Additionally, we present two cases of soft tissue sarcomas in an 18-year-old female patient and in a 71-year-old female patient, which were treated with extended external hemipelvectomies with anterior flap, in combination with an abdominoperineal amputation and a colostomy in one case. Results: After 4 years of follow-up, case 1 is living a relatively normal life. She had an uncomplicated pregnancy and a cesarean section delivery. Case 2 underwent emergency surgery for intestinal perforation and sepsis. She died 2.5 months following the surgery. Conclusions: External hemipelvectomy for soft tissue sarcoma treatment is a demanding surgical procedure with purpose in selected cases after review by multidisciplinary committees and with informed patient consent. This should be similarly individualized and extended to other pathologies when possible. Full article

(This article belongs to the Special Issue Interdisciplinary Approach to Soft Tissue Sarcoma Care: Bridging Gaps for Better Outcomes)

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12 pages, 2047 KiB

Open AccessArticle

The Prognostic Impact of Adipophilin Expression on Long-Term Survival Following Liver Resection in Patients with Colorectal Liver Metastases

by Tung Thanh Lai, Mitsuaki Ishida, Hisashi Kosaka, Kosuke Matsui, Hideyuki Matsushima, Hidekazu Yamamoto, Gozo Kiguchi, Khanh Van Nguyen, Kyoko Inoue, Moriyasu Takada, Hiroki Kato, Yoshinobu Hirose, Kengo Yoshii and Masaki Kaibori

Cancers 2024, 16(22), 3827; https://doi.org/10.3390/cancers16223827 - 14 Nov 2024

Abstract

Background/Objectives: Adipophilin (ADP) is a protein associated with lipid droplets, and its expression is related to poor prognosis in certain cancers. However, its impact on the survival of patients with colorectal liver metastases (CRLMs) remains unclear. This study investigated the impact of [...] Read more.

Background/Objectives: Adipophilin (ADP) is a protein associated with lipid droplets, and its expression is related to poor prognosis in certain cancers. However, its impact on the survival of patients with colorectal liver metastases (CRLMs) remains unclear. This study investigated the impact of ADP expression on long-term survival following hepatectomy in patients with CRLM. Methods: We retrospectively analyzed 102 consecutive patients who underwent hepatectomy between 2006 and 2022. ADP expression was examined in resected specimens through immunohistochemical staining using tissue microarrays. Long-term outcomes for ADP-positive (n = 51) and ADP-negative (n = 51) groups were compared with Kaplan–Meier survival analysis. Results: We found significantly decreased 5-year recurrence-free survival (RFS) and overall survival (OS) rates for ADP-positive patients relative to ADP-negative patients (29.4% versus 52.1%, respectively; p = 0.001 and 43.7% versus 72.2%, respectively; p = 0.003). Moreover, multivariate Cox hazards analysis demonstrated that patients with ADP-positive CRLM had a worse prognosis after hepatectomy than those with ADP-negative CRLM, as reflected by both RFS (HR 2.46, 95% CI 1.39–4.36, p = 0.002) and OS (HR: 2.89, 95% CI 1.43–5.85, p = 0.003). Conclusions: ADP expression had a significant prognostic impact on the survival of patients with CRLM following liver resection and may aid in optimal treatment planning. Full article

(This article belongs to the Special Issue Oncology: State-of-the-Art Research and Initiatives in Japan)

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