Cancers

15 pages, 1515 KiB

Open AccessSystematic Review

Secondary Cytoreductive Surgery in Relapsed Platinum-Sensitive Epithelial Ovarian Cancer: A Systematic Review of Randomized Controlled Trials

by Andrea Svennevik Myhr, Line Bjørge and Cecilie Fredvik Torkildsen

Cancers 2024, 16(14), 2613; https://doi.org/10.3390/cancers16142613 - 22 Jul 2024

Cited by 1 | Viewed by 1233

Abstract

Secondary cytoreductive surgery is a treatment option for relapsed platinum-sensitive epithelial ovarian cancer, but no clear indications are defined for the procedure. This systematic review aims to establish clear indications and compare outcomes versus standard-of-care chemotherapy. We conducted an electronic literature search across [...] Read more.

Secondary cytoreductive surgery is a treatment option for relapsed platinum-sensitive epithelial ovarian cancer, but no clear indications are defined for the procedure. This systematic review aims to establish clear indications and compare outcomes versus standard-of-care chemotherapy. We conducted an electronic literature search across three databases and identified 2033 articles, including three phase 3 randomized controlled trials (RCT). The review adhered to PRISMA 2020 guidelines and was registered in PROSPERO (no. CRD42022379817). Despite varying patient selection methods, surgery plus chemotherapy demonstrated significantly prolonged progression-free survival compared to chemotherapy alone. However, overall survival outcomes were inconsistent: while GOG-0213 did not show extended overall survival, recent studies with stricter defined criteria for surgery (SOC-1 and DESKTOP-III) reported improved overall survival with the addition of surgery. Morbidity and mortality rates were low, with no difference in quality of life between the surgery and no-surgery groups. In conclusion, cytoreductive surgery presents a promising option for recurrent epithelial ovarian cancer treatment. Nonetheless, well-defined selection criteria appear crucial for achieving increased overall survival compared to conventional treatment. Full article

(This article belongs to the Special Issue Recent Advances in Ovarian Cancer Surgery)

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24 pages, 4495 KiB

Open AccessArticle

Maintenance Therapy for Pancreatic Cancer, a New Approach Based on the Synergy between the Novel Agent GP-2250 (Misetionamide) and Gemcitabine

by Marie Buchholz, Britta Majchrzak-Stiller, Ilka Peters, Stephan Hahn, Lea Skrzypczyk, Lena Beule, Waldemar Uhl, Chris Braumann, Johanna Strotmann and Philipp Höhn

Cancers 2024, 16(14), 2612; https://doi.org/10.3390/cancers16142612 - 22 Jul 2024

Viewed by 981

Abstract

The novel Oxathiazinane derivative GP-2250 (Misetionamide) displays antineoplastic activity in vitro and in vivo, as previously shown in pancreatic cancer cells and in patient-derived mouse xenografts (PDX). Currently, GP 2250 is under phase I clinical trial in pancreatic ductal adenocarcinoma (PDAC). GP-2250 in [...] Read more.

The novel Oxathiazinane derivative GP-2250 (Misetionamide) displays antineoplastic activity in vitro and in vivo, as previously shown in pancreatic cancer cells and in patient-derived mouse xenografts (PDX). Currently, GP 2250 is under phase I clinical trial in pancreatic ductal adenocarcinoma (PDAC). GP-2250 in combination with Gemcitabine displays a high synergistic capacity in various primary and established pancreatic cancer cell lines. Additionally, in the eight PDX models tested, the drug combination was superior in reducing tumor volume with an aggregate tumor regression (ATR) of 74% compared to Gemcitabine alone (ATR: 10%). Similarly, in a PDX maintenance setting following two weeks of treatment with nab-Paclitaxel plus Gemcitabine, the combination of GP-2250 plus Gemcitabine resulted in outstanding tumor control (ATR: 79%) compared to treatment with Gemcitabine alone (ATR: 60%). Furthermore, GP-2250 reduced the ratio of tumor-initiating CD133⁺ markers on the surface of PDAC cells in spheroid cultures, indicating a possible mechanism for the synergistic effect of both substances. Considering the high tolerability of GP 2250, these results may open up a new approach to maintenance therapy with GP-2250/Gemcitabine combination following nab-Paclitaxel plus Gemcitabine as first-line treatment. Full article

(This article belongs to the Section Cancer Drug Development)

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14 pages, 2641 KiB

Open AccessArticle

Neurocognitive Adverse Events Related to Lorlatinib in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

by Jonathan N. Priantti, Maysa Vilbert, Francisco Cezar Aquino de Moraes, Thiago Madeira, Evair Moisés de Lima Santiago, Natasha B. Leighl, Ludimila Cavalcante and Nagla F. Abdel Karim

Cancers 2024, 16(14), 2611; https://doi.org/10.3390/cancers16142611 - 22 Jul 2024

Cited by 1 | Viewed by 1279

Abstract

Lorlatinib has been FDA-approved as a systemic therapy for ALK/ROS1-positive non-small cell lung cancer (NSCLC) patients. However, it has been associated with an increased frequency of neurocognitive adverse events (NAEs). Therefore, we conducted a systematic review and meta-analysis to assess the NAEs related [...] Read more.

Lorlatinib has been FDA-approved as a systemic therapy for ALK/ROS1-positive non-small cell lung cancer (NSCLC) patients. However, it has been associated with an increased frequency of neurocognitive adverse events (NAEs). Therefore, we conducted a systematic review and meta-analysis to assess the NAEs related to lorlatinib therapy in NSCLC patients. PubMed, Scopus, the Cochrane Library, and prominent conference proceedings were searched for eligible studies of lorlatinib in NSCLC patients. NAEs included cognitive, mood, speech, and psychotic effects. A total of 1147 patients from 12 studies were included; 62% had brain metastases. A pooled analysis of NAEs showed frequencies of cognitive effects of 14.57% (95% CI, 8.37 to 24.14, I2 = 84%), mood effects of 11.17% (95% CI, 5.93 to 20.07, I2 = 84%), speech effects of 7.24% (95% CI, 3.39 to 15.20, I2 = 72%), and psychotic effects of 4.97% (95% CI, 3.27 to 7.49, I2 = 21%). Clinical trials reported a significantly higher frequency of mood effects than was indicated by real-world data. These results highlight the importance of educating patients and healthcare professionals about lorlatinib-related NAEs for early detection and management to improve NSCLC patients’ quality of life. Full article

(This article belongs to the Special Issue Cancer-Therapy-Related Adverse Events)

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Graphical abstract

9 pages, 462 KiB

Open AccessCommentary

Alectinib in Early-Stage Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: Current Evidence and Future Challenges

by Diego Luigi Cortinovis, Alessandro Leonetti, Alessandro Morabito, Luca Sala and Marcello Tiseo

Cancers 2024, 16(14), 2610; https://doi.org/10.3390/cancers16142610 - 22 Jul 2024

Viewed by 1005

Abstract

Background: Targeted therapies changed the treatment of advanced oncogene-addicted non-small cell lung cancer and could also improve outcomes in resectable disease. Results: The ALINA trial evaluated the clinical benefit of adjuvant alectinib compared with standard chemotherapy and met the primary endpoint with a [...] Read more.

Background: Targeted therapies changed the treatment of advanced oncogene-addicted non-small cell lung cancer and could also improve outcomes in resectable disease. Results: The ALINA trial evaluated the clinical benefit of adjuvant alectinib compared with standard chemotherapy and met the primary endpoint with a significant increase in disease-free survival at 2 years among anaplastic lymphoma kinase positive patients with stage IB-IIIA disease; two phase II trials (ALNEO and NAUTIKA1) are currently evaluating perioperative treatment with alectinib, and the results of the case reports published to date are encouraging. Conclusion: In resectable anaplastic lymphoma kinase-positive lung cancer, adjuvant alectinib represents the new standard of care and could soon be used in perioperative treatment. Full article

(This article belongs to the Section Cancer Therapy)

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26 pages, 1560 KiB

Open AccessReview

Exploring the Role of GITR/GITRL Signaling: From Liver Disease to Hepatocellular Carcinoma

by Stavros P. Papadakos, Elena Chatzikalil, Georgios Vakadaris, Lampros Reppas, Konstantinos Arvanitakis, Theocharis Koufakis, Spyros I. Siakavellas, Spilios Manolakopoulos, Georgios Germanidis and Stamatios Theocharis

Cancers 2024, 16(14), 2609; https://doi.org/10.3390/cancers16142609 - 22 Jul 2024

Viewed by 1731

Abstract

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and presents a continuously growing incidence and high mortality rates worldwide. Besides advances in diagnosis and promising results of pre-clinical studies, established curative therapeutic options for HCC are not currently available. Recent progress [...] Read more.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and presents a continuously growing incidence and high mortality rates worldwide. Besides advances in diagnosis and promising results of pre-clinical studies, established curative therapeutic options for HCC are not currently available. Recent progress in understanding the tumor microenvironment (TME) interactions has turned the scientific interest to immunotherapy, revolutionizing the treatment of patients with advanced HCC. However, the limited number of HCC patients who benefit from current immunotherapeutic options creates the need to explore novel targets associated with improved patient response rates and potentially establish them as a part of novel combinatorial treatment options. Glucocorticoid-induced TNFR-related protein (GITR) belongs to the TNFR superfamily (TNFRSF) and promotes CD8⁺ and CD4⁺ effector T-cell function with simultaneous inhibition of Tregs function, when activated by its ligand, GITRL. GITR is currently considered a potential immunotherapy target in various kinds of neoplasms, especially with the concomitant use of programmed cell-death protein-1 (PD-1) blockade. Regarding liver disease, a high GITR expression in liver progenitor cells has been observed, associated with impaired hepatocyte differentiation, and decreased progenitor cell-mediated liver regeneration. Considering real-world data proving its anti-tumor effect and recently published evidence in pre-clinical models proving its involvement in pre-cancerous liver disease, the idea of its inclusion in HCC therapeutic options theoretically arises. In this review, we aim to summarize the current evidence supporting targeting GITR/GITRL signaling as a potential treatment strategy for advanced HCC. Full article

(This article belongs to the Special Issue Molecular Markers and Targeted Therapy for Hepatobiliary Tumors)

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46 pages, 3150 KiB

Open AccessReview

The Spectrum of CAR Cellular Effectors: Modes of Action in Anti-Tumor Immunity

by Ngoc Thien Thu Nguyen, Rasmus Müller, Daria Briukhovetska, Justus Weber, Judith Feucht, Annette Künkele, Michael Hudecek and Sebastian Kobold

Cancers 2024, 16(14), 2608; https://doi.org/10.3390/cancers16142608 - 22 Jul 2024

Viewed by 2223

Abstract

Chimeric antigen receptor-T cells have spearheaded the field of adoptive cell therapy and have shown remarkable results in treating hematological neoplasia. Because of the different biology of solid tumors compared to hematological tumors, response rates of CAR-T cells could not be transferred to [...] Read more.

Chimeric antigen receptor-T cells have spearheaded the field of adoptive cell therapy and have shown remarkable results in treating hematological neoplasia. Because of the different biology of solid tumors compared to hematological tumors, response rates of CAR-T cells could not be transferred to solid entities yet. CAR engineering has added co-stimulatory domains, transgenic cytokines and switch receptors to improve performance and persistence in a hostile tumor microenvironment, but because of the inherent cell type limitations of CAR-T cells, including HLA incompatibility, toxicities (cytokine release syndrome, neurotoxicity) and high costs due to the logistically challenging preparation process for autologous cells, the use of alternative immune cells is gaining traction. NK cells and γδ T cells that do not need HLA compatibility or macrophages and dendritic cells with additional properties such as phagocytosis or antigen presentation are increasingly seen as cellular vehicles with potential for application. As these cells possess distinct properties, clinicians and researchers need a thorough understanding of their peculiarities and commonalities. This review will compare these different cell types and their specific modes of action seen upon CAR activation. Full article

(This article belongs to the Special Issue CAR T Cell Therapy for Cancers)

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Graphical abstract

4 pages, 157 KiB

Open AccessEditorial

Innovative Imaging Techniques for Advancing Cancer Diagnosis and Treatment

by Tianyuan Wang, Yicheng Ni and Li Liu

Cancers 2024, 16(14), 2607; https://doi.org/10.3390/cancers16142607 - 22 Jul 2024

Viewed by 1503

Abstract

Traditional oncology image-analysis, using modalities such as echography, X-ray, CT, and MRI, has historically relied on human-defined features to interpret and assess clinical images [...] Full article

(This article belongs to the Special Issue Recent Advances in Oncology Imaging)

14 pages, 990 KiB

Open AccessArticle

PD-L1 Expression in Paired Samples of Rectal Cancer

by Mina Coussement, Roberta Fazio, Alessandro Audisio, Reem El Khoury, Fatima-Zahra Abbassi, Irene Assaf, Chiara Conti, Chiara Gallio, Nada Benhima, Giacomo Bregni, Paraskevas Gkolfakis, Valentina Spagnolo, Geraldine Anthoine, Gabriel Liberale, Luigi Moretti, Philippe Martinive, Alain Hendlisz, Pieter Demetter and Francesco Sclafani

Cancers 2024, 16(14), 2606; https://doi.org/10.3390/cancers16142606 - 21 Jul 2024

Viewed by 1132

Abstract

Immune checkpoint inhibitors and immune-related biomarkers are increasingly investigated in rectal cancer (RC). We retrospectively analysed PD-L1 expression in diagnostic biopsy and resection samples from RC patients treated at our centre between 2000 and 2020. PD-L1 immunostaining (22C3 clone) was evaluated according to [...] Read more.

Immune checkpoint inhibitors and immune-related biomarkers are increasingly investigated in rectal cancer (RC). We retrospectively analysed PD-L1 expression in diagnostic biopsy and resection samples from RC patients treated at our centre between 2000 and 2020. PD-L1 immunostaining (22C3 clone) was evaluated according to tumour proportion (TPS), immune cell (ICS), and the combined positive score (CPS). Eighty-three patients were included. At diagnosis, PD-L1 expression ≥1%/≥5% was observed in 15.4%/0%, 80.7%/37.4%, and 69.2%/25.6% of patients based on TPS, ICS, and CPS, respectively. At surgery, the respective figures were 4.6%/1.5%, 60.2%/32.5%, and 50.7%/26.2%. Using the 1% cut-off and regardless of the scoring system, PD-L1 was less expressed in surgery than biopsy samples (p ≤ 0.04). In paired specimens, PD-L1-ICS reduction was especially observed following neoadjuvant long-course (chemo)radiotherapy (p = 0.03). PD-L1-ICS of ≥5% in surgical samples (HR: 0.17; p = 0.02), and a biopsy-to-surgery increase in PD-L1-ICS (HR: 0.19; p = 0.04) was predictive for longer disease-free survival, while the PD-L1-ICS of either ≥1% (HR 0.28; p = 0.04) or ≥5% (HR 0.19; p = 0.03) in surgical samples and the biopsy-to-surgery increase in PD-L1-ICS (HR: 0.20; p = 0.04) were associated with better overall survival. Our study suggests that PD-L1 expression in RC is largely reflective of immune cell infiltration, and its presence/increase in surgical samples predicts better outcomes. Full article

(This article belongs to the Special Issue Current Status, Challenges and Future of Precision Medicine for Colorectal Cancer)

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12 pages, 700 KiB

Open AccessArticle

Protective Effect of Minimally Invasive Approach on Postoperative Peak Transaminase Following Liver Resection: A Single-Center Propensity Score-Based Analysis

by Francesco Ardito, Sara Ingallinella, Quirino Lai, Francesco Razionale, Davide De Sio, Caterina Mele, Simone Vani, Maria Vellone and Felice Giuliante

Cancers 2024, 16(14), 2605; https://doi.org/10.3390/cancers16142605 - 21 Jul 2024

Viewed by 662

Abstract

Background: Postoperative serum ALT levels are one of the most frequently used marker to detect liver tissue damage following liver resection. The aim of this study was to evaluate if minimally invasive liver surgery (MILS) may result in less hepatic injury than open [...] Read more.

Background: Postoperative serum ALT levels are one of the most frequently used marker to detect liver tissue damage following liver resection. The aim of this study was to evaluate if minimally invasive liver surgery (MILS) may result in less hepatic injury than open hepatectomy by assessing the differences of postoperative ALT levels. Methods: Patients who underwent MILS between 2009 and 2019 at our unit were included and compared with open liver resections. Median ALT levels was measured on postoperative day (POD) 1, 3 and 5. Postoperative peak transaminase (PPT) of ALT was determined on POD 1. The stabilized inverse probability treatment weighing (SIPTW) process was used to balance the two groups. A multivariable logistic regression analysis was used to analyze factors associated with high PPT. Results: After SIPTW, 292 MILS were compared with 159 open resections. Median ALT levels on POD 1, 3 and 5 were significantly higher in the open group than in the MILS group (301 vs. 187, p = 0.002; 180 vs. 121, p < 0.0001; 104 vs. 60, p < 0.0001; respectively). At the multivariable logistic regression analysis, MILS showed a protective effect for high PPT. Conclusions: MILS was associated with significantly lower postoperative ALT levels compared with open liver resections. MILS showed a protective effect for high PPT. Full article

(This article belongs to the Special Issue The Evolving Treatment and Clinical Trials of Hepatocellular Carcinoma)

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24 pages, 9818 KiB

Open AccessArticle

Recombinant Human TSH Fails to Induce the Proliferation and Migration of Papillary Thyroid Carcinoma Cell Lines

by Georgios Kalampounias, Athina Varemmenou, Christos Aronis, Irene Mamali, Athanasios-Nasir Shaukat, Dionysios V. Chartoumpekis, Panagiotis Katsoris and Marina Michalaki

Cancers 2024, 16(14), 2604; https://doi.org/10.3390/cancers16142604 - 21 Jul 2024

Viewed by 1060

Abstract

Thyrotropin (TSH) suppression is required in the management of patients with papillary thyroid carcinoma (PTC) to improve their outcomes, inevitably causing iatrogenic thyrotoxicosis. Nevertheless, the evidence supporting this practice remains limited and weak, and in vitro studies examining the mitogenic effects of TSH [...] Read more.

Thyrotropin (TSH) suppression is required in the management of patients with papillary thyroid carcinoma (PTC) to improve their outcomes, inevitably causing iatrogenic thyrotoxicosis. Nevertheless, the evidence supporting this practice remains limited and weak, and in vitro studies examining the mitogenic effects of TSH in cancerous cells used supraphysiological doses of bovine TSH, which produced conflicting results. Our study explores, for the first time, the impact of human recombinant thyrotropin (rh-TSH) on human PTC cell lines (K1 and TPC-1) that were transformed to overexpress the thyrotropin receptor (TSHR). The cells were treated with escalating doses of rh-TSH under various conditions, such as the presence or absence of insulin. The expression levels of TSHR and thyroglobulin (Tg) were determined, and subsequently, the proliferation and migration of both transformed and non-transformed cells were assessed. Under the conditions employed, rh-TSH was not adequate to induce either the proliferation or the migration rate of the cells, while Tg expression was increased. Our experiments indicate that clinically relevant concentrations of rh-TSH cannot induce proliferation and migration in PTC cell lines, even after the overexpression of TSHR. Further research is warranted to dissect the underlying molecular mechanisms, and these results could translate into better management of treatment for PTC patients. Full article

(This article belongs to the Section Molecular Cancer Biology)

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15 pages, 7970 KiB

Open AccessArticle

Radium-223 Treatment Produces Prolonged Suppression of Resident Osteoblasts and Decreased Bone Mineral Density in Trabecular Bone in Osteoblast Reporter Mice

by Song-Chang Lin, Guoyu Yu, Paul G. Corn, Jossana Damasco, Yu-Chen Lee, Jian H. Song, Nora M. Navone, Christopher J. Logothetis, Marites P. Melancon, Theocharis Panaretakis and Sue-Hwa Lin

Cancers 2024, 16(14), 2603; https://doi.org/10.3390/cancers16142603 - 21 Jul 2024

Viewed by 1045

Abstract

Radium 223 (Ra-223) is an α-emitting bone-homing radiopharmaceutical that targets tumor-induced osteoblasts and is used to reduce bone pain and prolong overall survival in men with bone-metastatic, castrate-resistant prostate cancer. However, increased fracture risk in skeletal sites with no bone metastasis has been [...] Read more.

Radium 223 (Ra-223) is an α-emitting bone-homing radiopharmaceutical that targets tumor-induced osteoblasts and is used to reduce bone pain and prolong overall survival in men with bone-metastatic, castrate-resistant prostate cancer. However, increased fracture risk in skeletal sites with no bone metastasis has been observed in patients treated with Ra-223. Both luciferase- or green fluorescence protein (GFP)-labeled osteoblast reporter mice were used to monitor the effect of Ra-223 on resident osteoblasts and normal bone structure. Upon Ra-223 treatment, 70% of resident osteoblasts were reduced within 2 days, and the osteoblast reduction lasted for at least 18 weeks without detectable recovery, as measured by in vivo bioluminescent imaging. In GFP-labeled osteoblast reporter mice, Ra-223 mainly reduced osteoblasts localized in the trabecular bone areas; the osteoblasts in the growth plates were less affected. Micro-computed tomography analyses showed that Ra-223 significantly reduced bone mineral density and bone microstructure in the trabecular area of femurs but not in the cortical bone. Tumor-induced bone was generated by inoculating osteogenic TRAMP-BMP4 prostate cancer cells into the mouse femurs; Ra-223 treatment significantly reduced tumor-induced osteoblasts. Our study shows that Ra-223 affects bone structures that are not involved in bone metastasis. Strategies that improve bone health may reduce fracture risk in patients receiving Ra-223. Full article

(This article belongs to the Section Tumor Microenvironment)

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12 pages, 945 KiB

Open AccessArticle

Initial Age and Performans Status: Predicators for Re-Irradiation Ability in Patients with Relapsed Brain Metastasis after Initial Stereotactic Radiotherapy

by Isabelle Chambrelant, Laure Kuntz, Clara Le Fèvre, Delphine Jarnet, Julian Jacob and Georges Noël

Cancers 2024, 16(14), 2602; https://doi.org/10.3390/cancers16142602 - 21 Jul 2024

Viewed by 799

Abstract

Background: Brain metastases (BMs) frequently occur in cancer patients, and stereotactic radiation therapy (SRT) is a preferred treatment option. In this retrospective study, we analyzed patients treated by SRT for a single BM during their first SRT session and we compared two subgroups: [...] Read more.

Background: Brain metastases (BMs) frequently occur in cancer patients, and stereotactic radiation therapy (SRT) is a preferred treatment option. In this retrospective study, we analyzed patients treated by SRT for a single BM during their first SRT session and we compared two subgroups: “Cohort 1” with patients did not undergo cerebral re-irradiation and “Cohort 2” with patients received at least one subsequent SRT session for cerebral recurrence. Methods: We included patients who received SRT for a single BM between January 2010 and June 2020. Cohort 1 comprised 152 patients, and Cohort 2 had 46 patients. Results: Cohort 2 exhibited younger patients with higher Karnofsky performance status (KPS). Median overall survival was considerably longer in Cohort 2 (21.8 months) compared to Cohort 1 (6.1 months). Local and cerebral recurrence rates were significantly higher in Cohort 2 (p < 0.001), attributed to patient selection and longer survival. The combined score of age and KPS proved to be a predictive factor for survival, with patients under 65 years of age and KPS > 80 showing the best survival rates in the overall population. Conclusion: This retrospective study highlights that the combined score of age and KPS can predict better survival, especially for patients under 65 years with a KPS score above 80. Further research involving larger and more diverse populations is essential to validate and expand upon these findings. Full article

(This article belongs to the Special Issue The Challenge of the Treatment: Radiotherapy of Brain Metastases)

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9 pages, 218 KiB

Open AccessArticle

Sexual Function in Women Diagnosed with Hereditary Breast and Ovarian Cancer Syndrome

by Federico Ferrari, Juri Amonti, Andrea Giannini, Hooman Soleymani Majd, Valentina Zizioli, Giancarlo Tisi, Luigi Della Corte, Emma Bonetti, Elisa Gozzini and Franco Odicino

Cancers 2024, 16(14), 2601; https://doi.org/10.3390/cancers16142601 - 21 Jul 2024

Viewed by 1042

Abstract

Background: Hereditary breast and ovarian cancer syndrome (HBOC) predisposes women to an increased risk mainly of breast and tubo-ovarian cancer. The aim of the study is to investigate whether being diagnosed with HBOC syndrome is itself a risk factor for sexual dysfunction. Methods: [...] Read more.

Background: Hereditary breast and ovarian cancer syndrome (HBOC) predisposes women to an increased risk mainly of breast and tubo-ovarian cancer. The aim of the study is to investigate whether being diagnosed with HBOC syndrome is itself a risk factor for sexual dysfunction. Methods: An ad hoc questionnaire, including baseline demographic and clinical data, and the Sexual Function Questionnaire 28 (SFQ28) were administered to HBOC female carriers (study group) and to a control group. Results: After propensity score matching (1:1), we enrolled 202 women, 101 in the study group and 101 in the control group. In a multivariate analysis, we finally found that menopausal status was the only risk factor for a significant low score in the domains Desire (HR 0.66; CI95% 0.47–0.93; p = 0.017), Arousal (Lubrication) (HR 0.52; CI95% 0.34–0.80; p = 0.003), Arousal (Cognitive) (HR 0.64; CI95% 0.44–0.95; p = 0.027), and Orgasm (HR 0.33; CI95% (0.16–0.70; p = 0.004), independent of risk-reducing surgery for gynecological malignancy. Psycho-oncology support is a protective factor for the Enjoyment domain (HR 1.38; CI95% 1.05–1.81; p = 0.022). Conclusions: HBOC syndrome itself does not affect SFQ28 domains, while menopausal status significantly influences sexual health, with potential mitigating effects of psycho-oncological support. Full article

(This article belongs to the Section Methods and Technologies Development)

19 pages, 25601 KiB

Open AccessReview

Incidental Findings in Lung Cancer Screening

by Yenpo Lin, Khulan Khurelsukh, I-Gung Li, Chen-Te Wu, Yi-Ming Wu, Gigin Lin, Cheng-Hong Toh and Yung-Liang Wan

Cancers 2024, 16(14), 2600; https://doi.org/10.3390/cancers16142600 - 20 Jul 2024

Viewed by 1609

Abstract

While low-dose computed tomography (LDCT) for lung cancer screening (LCS) has been recognized for its effectiveness in reducing lung cancer mortality, it often simultaneously leads to the detection of incidental findings (IFs) unrelated to the primary screening indication. These IFs present diagnostic and [...] Read more.

While low-dose computed tomography (LDCT) for lung cancer screening (LCS) has been recognized for its effectiveness in reducing lung cancer mortality, it often simultaneously leads to the detection of incidental findings (IFs) unrelated to the primary screening indication. These IFs present diagnostic and management challenges, potentially causing unnecessary anxiety and further invasive diagnostic procedures for patients. This review article provides an overview of IFs encountered in LDCT, emphasizing their clinical significance and recommended management strategies. We categorize IFs based on their anatomical locations (intrathoracic–intrapulmonary, intrathoracic–extrapulmonary, and extrathoracic) and discuss the most common findings. We highlight the importance of utilizing guidelines and standardized reporting systems by the American College of Radiology (ACR) to guide appropriate follow-ups. For each category, we present specific IF examples, their radiologic features, and the suggested management approach. This review aims to provide radiologists and clinicians with a comprehensive understanding of IFs in LCS for accurate assessment and management, ultimately enhancing patient care. Finally, we outline a few key aspects for future research and development in managing IFs. Full article

(This article belongs to the Special Issue Lung Cancer: From Mechanisms of Action and Risk Factors in Disease Onset to Management)

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12 pages, 1492 KiB

Open AccessArticle

Collection of Rare Peripheral Nerve Tumors—Insights from the German Registry

by Nadja Grübel, Gregor Antoniadis, Anne-Kathrin Uerschels, Oliver Gembruch, Vera Marschal, Stefanie Deininger, Ralph König, Andrej Pala, Juliane Bremer, Nora F. Dengler, Melanie Reuter, Christian Rainer Wirtz and Maria Teresa Pedro

Cancers 2024, 16(14), 2599; https://doi.org/10.3390/cancers16142599 - 20 Jul 2024

Viewed by 866

Abstract

The most common peripheral nerve tumors are of a benign nature and include schwannoma or neurofibroma. In rare cases, other tumors or non-tumorous lesions can mimic peripheral nerve tumors clinically or radiologically. Based on data from the multicentric German Peripheral Nerve Tumor Registry [...] Read more.

The most common peripheral nerve tumors are of a benign nature and include schwannoma or neurofibroma. In rare cases, other tumors or non-tumorous lesions can mimic peripheral nerve tumors clinically or radiologically. Based on data from the multicentric German Peripheral Nerve Tumor Registry (PNTR), which encompasses current information on 315 surgically treated patients from three high-volume centers, we present 61 cases of rare tumors and lesions that mimic tumors associated with peripheral nerves. This cohort displays considerable heterogeneity, featuring a broad spectrum of morphological features and biological potentials. Histopathological diagnoses include various intrinsic peripheral nerve tumors such as malignant peripheral nerve tumors (MPNSTs) (n = 13), perineurioma (n = 17), and hybrid nerve sheath tumors (HPNSTs, comprising schwannoma/perineurioma and schwannoma/neurofibroma) (n = 14), as well as atypical neurofibromatous neoplasm with unknown biological potential (ANNUBP) (n = 1). Additionally, the cohort encompasses extrinsic tumorous lesions like lymphoma (n = 3), lymphangioma (n = 2), hemangioma (n = 2), solitary fibrous tumor (n = 2), metastatic disease (n = 1), and single cases of other rare tumor entities (n = 6). An overview of the underlying pathology, imaging features, and clinical presentation is provided, with a brief description of each entity. A definitive preoperative differentiation between benign peripheral nerve tumors and rare intrinsic and extrinsic tumors is often not possible. Clinical examination and subtle imaging clues can at least indicate the possibility of a rare entity. The basic requirement is close cooperation between radiologists, neurologists, neuropathologists, and neurosurgeons at a specialized center to develop a multidisciplinary concept and offer the patient the best therapeutic approaches. Full article

(This article belongs to the Section Cancer Pathophysiology)

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13 pages, 804 KiB

Open AccessSystematic Review

Management of Metastatic Renal Cell Carcinoma Following First-Line Immune Checkpoint Therapy Failure: A Systematic Review

by Fausto Petrelli, Ivano Vavassori, Mauro Rossitto and Lorenzo Dottorini

Cancers 2024, 16(14), 2598; https://doi.org/10.3390/cancers16142598 - 20 Jul 2024

Viewed by 1075

Abstract

Introduction: There is a significant gap in the literature concerning the effective management of second-line therapy for patients with metastatic renal cell carcinoma (RCC) who have received immune checkpoint inhibitors (ICIs). Most of the published articles were small multicenter series or phase 2 [...] Read more.

Introduction: There is a significant gap in the literature concerning the effective management of second-line therapy for patients with metastatic renal cell carcinoma (RCC) who have received immune checkpoint inhibitors (ICIs). Most of the published articles were small multicenter series or phase 2 studies. To our knowledge, a systematic review that comprehensively outlines the range of treatment options available for patients with metastatic RCC who do not respond to first-line ICIs has not yet been conducted. Our aim was to synthesize evidence on second-line therapies for patients with metastatic RCC after initial treatment with ICIs and to offer recommendations on the best treatment regimens based on the current literature. Material and Methods: We conducted a search in PubMed, Embase, and the Cochrane Library on 29 February 2024, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We selected articles that met the predetermined inclusion criteria (written in English, retrospective observational studies, prospective series, and randomized trials reporting second-line therapy for metastatic RCC after failure of ICI-based therapy). Relevant articles were identified in the reference lists. The main endpoint was the overall response rate (ORR), with the median progression-free survival (PFS) and overall survival (OS) as secondary endpoints. Results: We included 27 studies reporting the outcomes of 1970 patients. Salvage therapies were classified as targeted therapy (VEGFR TKIs) in 18 studies and ICIs in 8 studies. In studies where TKIs were the second line of choice, the pooled ORR was 34% (95% CI: 30.2–38%). In studies where ICIs, alone or in combination with TKIs, were used as second-line therapies, the ORR was 25.7% (95% CI: 15.7–39.2%). In studies where TKIs and ICIs were the second-line choices, the pooled median PFS values were 11.4 months (95% CI: 9.5–13.6 months) and 9.8 months (95% CI: 7.5–12.7 months), respectively. Conclusions: This systematic review shows that VEGFR TKIs and ICIs are effective second-line therapies following an initial treatment with anti-PD(L)1 alone or in combination. The treatment choice should be personalized, taking into account the patient’s response to first-line ICIs, the site of the disease, the type of first-line combination (with or without VEGFR TKIs), and the patient’s overall condition. Full article

(This article belongs to the Special Issue Advances in Drug Delivery for Cancer Therapy)

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24 pages, 2514 KiB

Open AccessSystematic Review

Chemotoxicity and Associated Risk Factors in Colorectal Cancer: A Systematic Review and Meta-Analysis

by Claire J. Han, Xia Ning, Christin E. Burd, Daniel J. Spakowicz, Fode Tounkara, Matthew F. Kalady, Anne M. Noonan, Susan McCabe and Diane Von Ah

Cancers 2024, 16(14), 2597; https://doi.org/10.3390/cancers16142597 - 20 Jul 2024

Cited by 1 | Viewed by 1289

Abstract

Background: Colorectal cancer (CRC) patients experience multiple types of chemotoxicity affecting treatment compliance, survival, and quality of life (QOL). Prior research shows clinician-reported chemotoxicity (i.e., grading scales or diagnostic codes) predicts rehospitalization and cancer survival. However, a comprehensive synthesis of clinician-reported chemotoxicity is [...] Read more.

Background: Colorectal cancer (CRC) patients experience multiple types of chemotoxicity affecting treatment compliance, survival, and quality of life (QOL). Prior research shows clinician-reported chemotoxicity (i.e., grading scales or diagnostic codes) predicts rehospitalization and cancer survival. However, a comprehensive synthesis of clinician-reported chemotoxicity is still lacking. Objectives: We conducted a systematic review and meta-analysis to determine chemotoxicity’s prevalence and risk factors in CRC. Methods: A systematic search from 2009 to 2024 yielded 30 studies for review, with 25 included in the meta-analysis. Results: Pooled prevalences of overall, non-hematological, and hematological moderate-to-severe toxicities were 45.7%, 39.2%, and 25.3%, respectively. The most common clinician-reported chemotoxicities were gastrointestinal (GI) toxicity (22.9%) and neuropathy or neutropenia (17.9%). Significant risk factors at baseline were malnutritional status, frailty, impaired immune or hepato-renal functions, short telomere lengths, low gut lactobacillus levels, age, female sex, aggressive chemotherapy, and low QOL. Age was associated with neutropenia (β: −1.44) and GI toxicity (β:1.85) (p-values < 0.01). Older adults (>65 y.o.) had higher prevalences of overall (OR: 1.14) and GI (OR: 1.65) toxicities, but a lower prevalence of neutropenia (OR: 0.65) than younger adults (p-values < 0.05). Conclusions. Our findings highlight the importance of closely monitoring and managing chemotoxicity in CRC patients receiving chemotherapy. Full article

(This article belongs to the Topic Advances in Colorectal Cancer Therapy)

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17 pages, 924 KiB

Open AccessSystematic Review

Multi-Omics Classification of Intrahepatic Cholangiocarcinoma: A Systematic Review and Meta-Analysis

by Laura Alaimo, Sara Boggio, Giovanni Catalano, Giuseppe Calderone, Edoardo Poletto, Mario De Bellis, Tommaso Campagnaro, Corrado Pedrazzani, Simone Conci and Andrea Ruzzenente

Cancers 2024, 16(14), 2596; https://doi.org/10.3390/cancers16142596 - 20 Jul 2024

Viewed by 1295

Abstract

Intrahepatic cholangiocarcinoma (ICC) is a heterogeneous disease characterized by a dismal prognosis. Various attempts have been made to classify ICC subtypes with varying prognoses, but a consensus has yet to be reached. This systematic review aims to gather relevant data on the multi-omics-based [...] Read more.

Intrahepatic cholangiocarcinoma (ICC) is a heterogeneous disease characterized by a dismal prognosis. Various attempts have been made to classify ICC subtypes with varying prognoses, but a consensus has yet to be reached. This systematic review aims to gather relevant data on the multi-omics-based ICC classification. The PubMed, Embase, and Cochrane databases were searched for terms related to ICC and multi-omics analysis. Studies that identified multi-omics-derived ICC subtypes and investigated clinicopathological predictors of long-term outcomes were included. Nine studies, which included 910 patients, were considered eligible. Mean 3- and 5-year overall survival were 25.7% and 19.6%, respectively, for the multi-omics subtypes related to poor prognosis, while they were 70.2% and 63.3%, respectively, for the subtypes linked to a better prognosis. Several negative prognostic factors were identified, such as genes’ expression profile promoting inflammation, mutations in the KRAS gene, advanced tumor stage, and elevated levels of oncological markers. The subtype with worse clinicopathological characteristics was associated with worse survival (Ref.: good prognosis subtype; pooled hazard ratio 2.06, 95%CI 1.67–2.53). Several attempts have been made to classify molecular ICC subtypes, but they have yielded heterogeneous results and need a clear clinical definition. More efforts are required to build a comprehensive classification system that includes both molecular and clinical characteristics before implementation in clinical practice to facilitate decision-making and select patients who may benefit the most from comprehensive molecular profiling in the disease’s earlier stages. Full article

(This article belongs to the Special Issue New Insights into the Management of Intrahepatic Cholangiocarcinoma)

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19 pages, 3062 KiB

Open AccessArticle

Fibroblasts Promote Resistance to KRAS Silencing in Colorectal Cancer Cells

by Susana Mendonça Oliveira, Patrícia Dias Carvalho, André Serra-Roma, Patrícia Oliveira, Andreia Ribeiro, Joana Carvalho, Flávia Martins, Ana Luísa Machado, Maria José Oliveira and Sérgia Velho

Cancers 2024, 16(14), 2595; https://doi.org/10.3390/cancers16142595 - 20 Jul 2024

Viewed by 1429

Abstract

Colorectal cancer (CRC) responses to KRAS-targeted inhibition have been limited due to low response rates, the mechanisms of which remain unknown. Herein, we explored the cancer-associated fibroblasts (CAFs) secretome as a mediator of resistance to KRAS silencing. CRC cell lines HCT15, HCT116, and [...] Read more.

Colorectal cancer (CRC) responses to KRAS-targeted inhibition have been limited due to low response rates, the mechanisms of which remain unknown. Herein, we explored the cancer-associated fibroblasts (CAFs) secretome as a mediator of resistance to KRAS silencing. CRC cell lines HCT15, HCT116, and SW480 were cultured either in recommended media or in conditioned media from a normal colon fibroblast cell line (CCD-18Co) activated with rhTGF-β1 to induce a CAF-like phenotype. The expression of membrane stem cell markers was analyzed by flow cytometry. Stem cell potential was evaluated by a sphere formation assay. RNAseq was performed in KRAS-silenced HCT116 colonospheres treated with either control media or conditioned media from CAFs. Our results demonstrated that KRAS-silencing up-regulated CD24 and down-regulated CD49f and CD104 in the three cell lines, leading to a reduction in sphere-forming efficiency. However, CAF-secreted factors restored stem cell marker expression and increased stemness. RNA sequencing showed that CAF-secreted factors up-regulated genes associated with pro-tumorigenic pathways in KRAS-silenced cells, including KRAS, TGFβ, NOTCH, WNT, MYC, cell cycle progression and exit from quiescence, epithelial-mesenchymal transition, and immune regulation. Overall, our results suggest that resistance to KRAS-targeted inhibition might derive not only from cell-intrinsic causes but also from external elements, such as fibroblast-secreted factors. Full article

(This article belongs to the Special Issue RAS Signaling Pathway in Cancer Therapy)

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14 pages, 2993 KiB

Open AccessArticle

LncRNA LOC730101 Promotes Darolutamide Resistance in Prostate Cancer by Suppressing miR-1-3p

by Tianyi Zhou, Steven Nguyen, Jacky Wu, Bin He and Qin Feng

Cancers 2024, 16(14), 2594; https://doi.org/10.3390/cancers16142594 - 20 Jul 2024

Cited by 1 | Viewed by 1025

Abstract

Antiandrogen is part of the standard-of-care treatment option for metastatic prostate cancer. However, prostate cancers frequently relapse, and the underlying resistance mechanism remains incompletely understood. This study seeks to investigate whether long non-coding RNAs (lncRNAs) contribute to the resistance against the latest antiandrogen [...] Read more.

Antiandrogen is part of the standard-of-care treatment option for metastatic prostate cancer. However, prostate cancers frequently relapse, and the underlying resistance mechanism remains incompletely understood. This study seeks to investigate whether long non-coding RNAs (lncRNAs) contribute to the resistance against the latest antiandrogen drug, darolutamide. Our RNA sequencing analysis revealed significant overexpression of LOC730101 in darolutamide-resistant cancer cells compared to the parental cells. Elevated LOC730101 levels were also observed in clinical samples of metastatic castration-resistant prostate cancer (CRPC) compared to primary prostate cancer samples. Silencing LOC730101 with siRNA significantly impaired the growth of darolutamide-resistant cells. Additional RNA sequencing analysis identified a set of genes regulated by LOC730101, including key players in the cell cycle regulatory pathway. We further demonstrated that LOC730101 promotes darolutamide resistance by competitively inhibiting microRNA miR-1-3p. Moreover, by Hi-C sequencing, we found that LOC730101 is located in a topologically associating domain (TAD) that undergoes specific gene induction in darolutamide-resistant cells. Collectively, our study demonstrates the crucial role of the lncRNA LOC730101 in darolutamide resistance and its potential as a target for overcoming antiandrogen resistance in CRPC. Full article

(This article belongs to the Special Issue The Response of Prostate Cancers to Androgen Deprivation Therapies)

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25 pages, 9037 KiB

Open AccessReview

Imaging Recommendations for Diagnosis and Management of Primary Parathyroid Pathologies: A Comprehensive Review

by Nivedita Chakrabarty, Abhishek Mahajan, Sandip Basu and Anil K. D’Cruz

Cancers 2024, 16(14), 2593; https://doi.org/10.3390/cancers16142593 - 19 Jul 2024

Viewed by 1477

Abstract

Parathyroid pathologies are suspected based on the biochemical alterations and clinical manifestations, and the predominant roles of imaging in primary hyperparathyroidism are localisation of tumour within parathyroid glands, surgical planning, and to look for any ectopic parathyroid tissue in the setting of recurrent [...] Read more.

Parathyroid pathologies are suspected based on the biochemical alterations and clinical manifestations, and the predominant roles of imaging in primary hyperparathyroidism are localisation of tumour within parathyroid glands, surgical planning, and to look for any ectopic parathyroid tissue in the setting of recurrent disease. This article provides a comprehensive review of embryology and anatomical variations of parathyroid glands and their clinical relevance, surgical anatomy of parathyroid glands, differentiation between multiglandular parathyroid disease, solitary adenoma, atypical parathyroid tumour, and parathyroid carcinoma. The roles, advantages and limitations of ultrasound, four-dimensional computed tomography (4DCT), radiolabelled technetium-99 (^99mTc) sestamibi or dual tracer ^99mTc pertechnetate and ^99mTc-sestamibi with or without single photon emission computed tomography (SPECT) or SPECT/CT, dynamic enhanced magnetic resonance imaging (4DMRI), and fluoro-choline positron emission tomography (¹⁸F-FCH PET) or [¹¹C] Methionine (¹¹C -MET) PET in the management of parathyroid lesions have been extensively discussed in this article. The role of fluorodeoxyglucose PET (FDG-PET) has also been elucidated in this article. Management guidelines for parathyroid carcinoma proposed by the American Society of Clinical Oncology (ASCO) have also been described. An algorithm for management of parathyroid lesions has been provided at the end to serve as a quick reference guide for radiologists, clinicians and surgeons. Full article

(This article belongs to the Section Cancer Causes, Screening and Diagnosis)

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12 pages, 1806 KiB

Open AccessArticle

Baseline Blood CD8⁺ T Cell Activation Potency Discriminates Responders from Non-Responders to Immune Checkpoint Inhibition Combined with Stereotactic Radiotherapy in Non-Small-Cell Lung Cancer

by Hanneke Kievit, M. Benthe Muntinghe-Wagenaar, Wayel H. Abdulahad, Abraham Rutgers, Lucie B. M. Hijmering-Kappelle, Birgitta I. Hiddinga, J. Fred Ubbels, Robin Wijsman, Marcel J. van der Leij, Johan Bijzet, Harry J. M. Groen, Huib A. M. Kerstjens, Anthonie J. van der Wekken, Bart-Jan Kroesen and T. Jeroen N. Hiltermann

Cancers 2024, 16(14), 2592; https://doi.org/10.3390/cancers16142592 - 19 Jul 2024

Viewed by 972

Abstract

Background: Tumor-infiltrating immune cells have been correlated with prognosis for patients treated with immune checkpoint inhibitor (ICI) treatment of various cancers. However, no robust biomarker has been described to predict treatment response yet. We hypothesized that the activation potency of circulating T cells [...] Read more.

Background: Tumor-infiltrating immune cells have been correlated with prognosis for patients treated with immune checkpoint inhibitor (ICI) treatment of various cancers. However, no robust biomarker has been described to predict treatment response yet. We hypothesized that the activation potency of circulating T cells may predict response to ICI treatment. Methods: An exploratory analysis was conducted to investigate the association between the response to immune checkpoint inhibition (ICI) combined with stereotactic radiotherapy (SBRT) and the potency of circulating T cells to be activated. Blood-derived lymphocytes from 14 patients were stimulated ex vivo with, among others, Staphylococcal enterotoxin B (SEB) and compared to healthy controls (HCs). Patients were grouped into responders (>median progression free survival (PFS)) and non-responders (<median PFS). The expression of the T cell activation marker CD69 and intracellular cytokines (IL-2, IFNγ, TNFα) in both CD4⁺ and CD8⁺ T cells in response to stimulation was measured using flow cytometry. In addition, serum levels of BAFF, IFNγ, and IL-2 receptor (sIL-2R) were measured by Luminex. Results: At baseline, a higher percentage of activated CD8⁺ T cells (15.8% vs. 3.5% (p = <0.01)) and IL-2⁺CD69⁺CD8⁺ T cells (8.8% vs. 2.9% (p = 0.02)) was observed in responders compared to non-responders upon ex vivo stimulation with SEB. The concurrently measured serum cytokine levels were not different between responders and non-responders. Conclusion: Baseline blood CD8⁺ T cell activation potency, measured by intracellular cytokine production after ex vivo stimulation, is a potential biomarker to discriminate responders from non-responders to SBRT combined with ICI. Full article

(This article belongs to the Special Issue Novel Biomarkers in Non-Small Cell Lung Cancer (NSCLC))

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18 pages, 8772 KiB

Open AccessArticle

Characterization of a Syngeneic Orthotopic Model of Cholangiocarcinoma by [¹⁸F]FDG-PET/MRI

by Lena Zachhuber, Thomas Filip, Behrang Mozayani, Mathilde Löbsch, Stefan Scheiner, Petra Vician, Johann Stanek, Marcus Hacker, Thomas H. Helbich, Thomas Wanek, Walter Berger and Claudia Kuntner

Cancers 2024, 16(14), 2591; https://doi.org/10.3390/cancers16142591 - 19 Jul 2024

Viewed by 1089

Abstract

Cholangiocarcinoma (CCA) is a type of primary liver cancer originating from the biliary tract epithelium, characterized by limited treatment options for advanced cases and low survival rates. This study aimed to establish an orthotopic mouse model for CCA and monitor tumor growth using [...] Read more.

Cholangiocarcinoma (CCA) is a type of primary liver cancer originating from the biliary tract epithelium, characterized by limited treatment options for advanced cases and low survival rates. This study aimed to establish an orthotopic mouse model for CCA and monitor tumor growth using PET/MR imaging. Murine CCA cells were implanted into the liver lobe of male C57BL/6J mice. The imaging groups included contrast-enhanced (CE) MR, CE-MR with static [¹⁸F]FDG-PET, and dynamic [¹⁸F]FDG-PET. Tumor volume and FDG uptake were measured weekly over four weeks. Early tumor formation was visible in CE-MR images, with a gradual increase in volume over time. Dynamic FDG-PET revealed an increase in the metabolic glucose rate (MRGlu) over time. Blood analysis showed pathological changes in liver-related parameters. Lung metastases were observed in nearly all animals after four weeks. The study concludes that PET-MR imaging effectively monitors tumor progression in the CCA mouse model, providing insights into CCA development and potential treatment strategies. Full article

(This article belongs to the Special Issue Advances in Oncological Imaging)

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20 pages, 500 KiB

Open AccessArticle

Bevacizumab-Based Therapies in Malignant Tumors—Real-World Data on Effectiveness, Safety, and Cost

by Elena Chitoran, Vlad Rotaru, Sinziana-Octavia Ionescu, Aisa Gelal, Cristina-Mirela Capsa, Roxana-Elena Bohiltea, Madalina-Nicoleta Mitroiu, Dragos Serban, Giuseppe Gullo, Daniela-Cristina Stefan and Laurentiu Simion

Cancers 2024, 16(14), 2590; https://doi.org/10.3390/cancers16142590 - 19 Jul 2024

Cited by 1 | Viewed by 1312

Abstract

Overall, it is estimated that more than 3,500,000 patients have received Bevacizumab as part of systemic oncologic treatment. Bevacizumab and its biosimilars are currently marketed in over 130 countries. Given the wide usage of Bevacizumab in current oncological practice, it is very important [...] Read more.

Overall, it is estimated that more than 3,500,000 patients have received Bevacizumab as part of systemic oncologic treatment. Bevacizumab and its biosimilars are currently marketed in over 130 countries. Given the wide usage of Bevacizumab in current oncological practice, it is very important to compare the “real-world” results to those obtained in controlled clinical trials. This study aims to describe the clinical experience of using Bevacizumab in a large cohort of cancer patients in “non-controlled real-world” conditions with regard to effectiveness, safety, and cost of therapy. Methods: For this purpose, we conducted an open, observational, retrospective study involving all patients treated for solid malignant tumors in the Bucharest Institute of Oncology with “Prof. Dr. Al. Trestioreanu” with Bevacizumab-based systemic therapy, between 2017 and 2021. Results: The study consisted of 657 treatment episodes in 625 patients (F/B = 1.62/1, with a median age of 57.6 years) which were treated for malignant tumors (majority colorectal, non-small cell lung, ovarian, and breast cancer). First-line treatment was administered in 229 patients, and the rest received Bevacizumab as second or subsequent lines of treatment. The overall response rate to Bevacizumab-based therapies was around 60–65% across all indication except for subsequent treatment lines in colorectal and ovarian cancers, where lower values were recorded (27.1%, and 31.5% respectively). Median PFS for the entire cohort was 8.2 months (95% CI 6.8–9.6), and the median OS was 13.2 months (95% CI 11.5–14.9). Usual bevacizumab-related toxicities were observed, including bleeding, hypertension, wound-healing complications, gastrointestinal perforation, other types of fistulas, septic complications, and thromboembolic events. Although the clinical benefits are undeniable, the addition of Bevacizumab to standard chemotherapy increased the overall treatment cost by 213%. Conclusions: Bevacizumab remains a high-cost therapy, but it can add to clinical benefits (like overall survival, progression-free survival, and response rate) when used in conjunction with standard chemotherapy. Similar results as those presented in various controlled trials are observable even on unselected cohorts of patients in the uncontrolled conditions of “real-world” oncological practice. Off-label usage is encountered in clinical practice, and this aspect should be monitored given the potential adverse effects of the therapy. Full article

(This article belongs to the Special Issue Preclinical and Clinical Research on the Efficacy of Anticancer Drugs)

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13 pages, 1136 KiB

Open AccessArticle

Post-Progression Analysis of EGFR-Mutant NSCLC Following Osimertinib Therapy in Real-World Settings

by Ilaria Attili, Carla Corvaja, Gianluca Spitaleri, Pamela Trillo Aliaga, Ester Del Signore, Antonio Passaro and Filippo de Marinis

Cancers 2024, 16(14), 2589; https://doi.org/10.3390/cancers16142589 - 19 Jul 2024

Cited by 2 | Viewed by 1152

Abstract

Background: Platinum-based chemotherapy is the current standard treatment option in patients with EGFR-mutant non-small-cell lung cancer (NSCLC) who progress on osimertinib. However, outcomes with chemotherapy are dismal, and the treatment of central nervous system (CNS) disease is an unmet need in this [...] Read more.

Background: Platinum-based chemotherapy is the current standard treatment option in patients with EGFR-mutant non-small-cell lung cancer (NSCLC) who progress on osimertinib. However, outcomes with chemotherapy are dismal, and the treatment of central nervous system (CNS) disease is an unmet need in this setting. Methods: Patients with EGFR-mutant NSCLC who were candidates to receive osimertinib in the metastatic setting at our Center from 2015 to 2022 were retrospectively evaluated to identify patients who received standard platinum-based chemotherapy post-osimertinib. Data were collected on treatment outcomes, with a focus on brain metastases and progression patterns. Results: A total of 220 patients received indication for osimertinib in the study period; n = 176 had adequate follow-up data. Overall, n = 117 patients experienced disease progression on osimertinib. The median time to osimertinib progressive disease (PD) was 15 months (95% confidence interval CI 13–18). Of them, 51 patients (45%) had no access to further treatments. Of the remaining patients, n = 8 received experimental treatments, and n = 55 received standard platinum-based chemotherapy and were considered for this study. Median duration of chemotherapy was 3 months (95% CI 2–5); the best responses among 53 evaluable patients were observed as follows: 15% partial response/complete response (PR/CR), 40% stable disease (SD), 45% PD. Median progression-free survival (PFS) and overall survival (OS) were 3 (95% CI 2–5) and 10 (95% CI 6–15) months, respectively. All patients had baseline and follow-up brain radiologic assessments, and n = 23 had brain metastases at the start of chemotherapy. With a median follow-up of 13 months, intracranial PD occurred in 47% patients, being the first site of PD in 59% of cases. The median time for intracranial (IC) PD was 2 months (95% CI 2–7). IC PD occurred as oligometastatic in 29%, whereas in 71% of cases, it was associated with systemic PD. Conclusions: Access to subsequent treatments and CNS progression are confirmed unmet needs in EGFR-mutant NSCLC patients. Clinical and CNS-specific outcomes in patients receiving standard chemotherapy after the failure of osimertinib are dismal. Novel upfront treatment options with demonstrated prolonged PFS and better CNS outcomes may help address this important issue. Full article

(This article belongs to the Special Issue Advances in Epidermal Growth Factor Receptor-Driven Non-Small-Cell Lung Cancer: Diagnostic Technologies and Therapeutic Strategies)

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13 pages, 275 KiB

Open AccessArticle

Stem Cell Mobilization Performed with Different Doses of Cytarabine in Plasma Cell Myeloma Patients Relapsing after Previous Autologous Hematopoietic Cell Transplantation—A Multicenter Report by the Polish Myeloma Study Group

by Joanna Drozd-Sokołowska, Anna Waszczuk-Gajda, Magdalena Topczewska, Martyna Maciejewska, Magdalena Dutka, Jan Maciej Zaucha, Anna Szmigielska-Kapłon, Mateusz Nowicki, Magdalena Olszewska-Szopa, Agnieszka Szeremet, Anna Czyż, Magdalena Kozioł, Marek Hus, Joanna Mańko, Iwona Hus, Joanna Romejko-Jarosińska, Anna Kopińska, Grzegorz Helbig, Krzysztof Mądry, Piotr Boguradzki, Małgorzata Król, Emilian Snarski, Patrick J. Hayden, Krzysztof Jamroziak, Jadwiga Dwilewicz-Trojaczek and Grzegorz Władysław Basak Show full author list Hide full author list

Cancers 2024, 16(14), 2588; https://doi.org/10.3390/cancers16142588 - 19 Jul 2024

Viewed by 811

Abstract

Salvage autologous hematopoietic cell transplantation (auto-HCT) may be used to treat relapse of plasma cell myeloma occurring after previous auto-HCT. When an insufficient number of hematopoietic stem cells have been stored from the initial harvest, remobilization is necessary. Here, we aimed to analyze [...] Read more.

Salvage autologous hematopoietic cell transplantation (auto-HCT) may be used to treat relapse of plasma cell myeloma occurring after previous auto-HCT. When an insufficient number of hematopoietic stem cells have been stored from the initial harvest, remobilization is necessary. Here, we aimed to analyze the efficacy and safety of different doses of cytarabine (total 800 vs. 1600 vs. 2400 mg/m²) for remobilization. Sixty-five patients, 55% male, with a median age at remobilization 63 years, were included. Remobilization was performed with cytarabine_800 in 7, cytarabine_1600 in 36, and cytarabine_2400 in 22 patients. Plerixafor rescue was used in 25% of patients receiving cytarabine_1600 and 27% of those receiving cytarabine_2400. Patients administered cytarabine_800 were not rescued with plerixafor. Remobilization was successful in 80% of patients (57% cytarabine_800; 86% cytarabine_1600; 77% cytarabine_2400; p = 0.199). The yield of collected CD34+ cells did not differ between the different cytarabine doses (p = 0.495). Patients receiving cytarabine_2400 were at the highest risk of developing severe cytopenias, requiring blood product support, or having blood-stream infections. One patient died of septic shock after cytarabine_2400. In summary, remobilization with cytarabine is feasible in most patients. All doses of cytarabine allow for successful remobilization. Cytarabine_2400 is associated with higher toxicity; therefore, lower doses (800 or 1600 mg/m²) seem to be preferable. Full article

(This article belongs to the Special Issue Stem Cell Transplantation on Multiple Myeloma)

2 pages, 715 KiB

Open AccessCorrection

Correction: Krayem et al. Kinome Profiling to Predict Sensitivity to MAPK Inhibition in Melanoma and to Provide New Insights into Intrinsic and Acquired Mechanism of Resistance. Cancers 2020, 12, 512

by Mohammad Krayem, Philippe Aftimos, Ahmad Najem, Tim van den Hooven, Adriënne van den Berg, Liesbeth Hovestad-Bijl, Rik de Wijn, Riet Hilhorst, Rob Ruijtenbeek, Malak Sabbah, Joseph Kerger, Ahmad Awada, Fabrice Journe and Ghanem E. Ghanem

Cancers 2024, 16(14), 2587; https://doi.org/10.3390/cancers16142587 - 19 Jul 2024

Viewed by 496

Abstract

In the original article [...] Full article

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20 pages, 2539 KiB

Open AccessArticle

Real-World Treatment Patterns and Timeliness of Clinical Care Pathway for Non-Small Cell Lung Cancer Patients in Austria: The PRATER Retrospective Study

by Maximilian Hochmair, Angelika Terbuch, David Lang, Christian Trockenbacher, Florian Augustin, Bahil Ghanim, Dominik Maurer, Hossein Taghizadeh, Christoph Kamhuber, Robert Wurm, Jörg Lindenmann, Petra Braz, Tatjana Bundalo, Merjem Begic, Johanna Bauer, Patrick Reimann, Nino Müser, Florian Huemer, Verena Schlintl, Daniela Bianconi, Bernhard Baumgartner, Peter Schenk, Markus Rauter and Konrad Hötzenecker Show full author list Hide full author list

Cancers 2024, 16(14), 2586; https://doi.org/10.3390/cancers16142586 - 19 Jul 2024

Viewed by 1705

Abstract

This was a retrospective study of the profile and initial treatments of adults diagnosed with early-stage (ES) non-small cell lung cancer (NSCLC) during January 2018–December 2021 at 16 leading hospital institutions in Austria, excluding patients enrolled in clinical trials. In total, 319 patients [...] Read more.

This was a retrospective study of the profile and initial treatments of adults diagnosed with early-stage (ES) non-small cell lung cancer (NSCLC) during January 2018–December 2021 at 16 leading hospital institutions in Austria, excluding patients enrolled in clinical trials. In total, 319 patients were enrolled at a planned ~1:1:1 ratio across StI:II:III. Most tested biomarkers were programmed death ligand 1 (PD-L1; 58% expressing), Kirsten rat sarcoma virus (KRAS; 22% positive), and epidermal growth factor receptor (EGFR; 18% positive). Of 115/98/106 StI/II/III patients, 82%/85%/36% underwent surgery, followed by systemic therapy in 9%/45%/47% of those [mostly chemotherapy (ChT)]. Unresected treated StIII patients received ChT + radiotherapy [43%; followed by immune checkpoint inhibitors (ICIs) in 39% of those], ICI ± ChT (35%), and ChT-alone/radiotherapy-alone (22%). Treatment was initiated a median (interquartile range) of 24 (7–39) days after histological confirmation, and 55 (38–81) days after first medical visit. Based on exploratory analyses of all patients newly diagnosed with any stage NSCLC during 2018–2021 at 14 of the sites (N = 7846), 22%/10%/25%/43% had StI/II/III/IV. The total number was not significantly different between pre-COVID-19 (2018–2019) and study-specific COVID-19 (2020–2021) periods, while StI proportion increased (21% vs. 23%; p = 0.012). Small differences were noted in treatments. In conclusion, treatments were aligned with guideline recommendations at a time which preceded the era of ICIs and targeted therapies in the (neo)adjuvant setting. Full article

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

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30 pages, 10460 KiB

Open AccessReview

by Chiara Pozzessere, Bianca Mazini, Patrick Omoumi, Mario Jreige, Leslie Noirez, Antonia Digklia, François Fasquelle, Christine Sempoux and Clarisse Dromain

Cancers 2024, 16(14), 2585; https://doi.org/10.3390/cancers16142585 - 19 Jul 2024

Cited by 1 | Viewed by 1943

Abstract

Immunotherapy has revolutionized oncology care, improving patient outcomes in several cancers. However, these therapies are also associated with typical immune-related adverse events due to the enhanced inflammatory and immune response. These toxicities can arise at any time during treatment but are more frequent [...] Read more.

Immunotherapy has revolutionized oncology care, improving patient outcomes in several cancers. However, these therapies are also associated with typical immune-related adverse events due to the enhanced inflammatory and immune response. These toxicities can arise at any time during treatment but are more frequent within the first few months. Any organ and tissue can be affected, ranging from mild to life-threatening. While some manifestations are common and more often mild, such as dermatitis and colitis, others are rarer and more severe, such as myocarditis. Management depends on the severity, with treatment being held for >grade 2 toxicities. Steroids are used in more severe cases, and immunosuppressive treatment may be considered for non-responsive toxicities, along with specific organ support. A multidisciplinary approach is mandatory for prompt identification and management. The diagnosis is primarily of exclusion. It often relies on imaging features, and, when possible, cytologic and/or pathological analyses are performed for confirmation. In case of clinical suspicion, imaging is required to assess the presence, extent, and features of abnormalities and to evoke and rule out differential diagnoses. This imaging-based review illustrates the diverse system-specific toxicities associated with immune checkpoint inhibitors and chimeric antigen receptor T-cells with a multidisciplinary perspective. Clinical characteristics, imaging features, cytological and histological patterns, as well as the management approach, are presented with insights into radiological tips to distinguish these toxicities from the most important differential diagnoses and mimickers—including tumor progression, pseudoprogression, inflammation, and infection—to guide imaging and clinical specialists in the pathway of diagnosing immune-related adverse events. Full article

(This article belongs to the Special Issue How to Properly Diagnose and Treat Immune-Related Adverse Events during Immunotherapy in Patients with Cancer: Discussion between Specialists)

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Open AccessArticle

Impact of Robotic Assistance on Minimally Invasive Surgery for Type II Endometrial Cancer: A National Cancer Database Analysis

by Kelly Lamiman, Michael Silver, Nicole Goncalves, Michael Kim and Ioannis Alagkiozidis

Cancers 2024, 16(14), 2584; https://doi.org/10.3390/cancers16142584 - 19 Jul 2024

Viewed by 976

Abstract

The objective of this study is to compare the overall survival (OS) and surgical outcomes between conventional laparoscopy and robot-assisted laparoscopy (RAL) in women with type II endometrial cancer. We identified a large cohort of women who underwent hysterectomy for type II endometrial [...] Read more.

The objective of this study is to compare the overall survival (OS) and surgical outcomes between conventional laparoscopy and robot-assisted laparoscopy (RAL) in women with type II endometrial cancer. We identified a large cohort of women who underwent hysterectomy for type II endometrial cancer between January 2010 and December 2014 using the National Cancer Database (NCDB). The primary outcome was to compare the OS of conventional laparoscopy versus RAL. Secondary outcomes included the length of hospital stay, 30-day readmission rate, 90-day mortality, rates of lymph node retrieval, rates of node positivity, and rates of conversion to laparotomy. Cohorts were compared and multivariable logistic regression was used to determine characteristics with statistically significant predictors of outcome. We identified 7168 patients with stage I–III type II endometrial cancer who had minimally invasive surgery as primary treatment between 2010 and 2014. A total of 5074 patients underwent RAL. Women who underwent RAL were less likely to have stage III disease (26.4% vs. 29.9%, p = 0.008) and had smaller primary tumors (4.6 vs. 4.1 cm, p < 0.001). In a multivariable model, there was no difference in OS between conventional laparoscopy and RAL. With regard to postoperative outcomes, RAL was associated with a decreased risk for conversion to laparotomy (2.7% vs. 12%, p < 0.001), a shorter hospital stay (1 vs. 2 days, p < 0.001), a decreased 90-day mortality (1.3% vs. 2.2%, p = 0.004), and an increased number of lymph nodes sampled (14 vs. 12, p < 0.001). In multivariable analysis, the use of RAL was independently associated with a reduced rate of conversion to laparotomy. In conclusion, there was no difference in OS between conventional laparoscopy and RAL in type II endometrial cancer in a large retrospective cohort of patients from the NCDB. RAL was associated with a decreased risk of conversion to laparotomy. Full article

(This article belongs to the Special Issue Clinical Research Advances in Endometrial Carcinoma)

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Cancers, Volume 16, Issue 14 (July-2 2024) – 121 articles

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