Cancers

15 pages, 836 KiB

Open AccessArticle

Long-Term Survival, Prognostic Factors, and Quality of Life of Patients Undergoing Pelvic Exenteration for Cervical Cancer

by Mihai Stanca, Dan Mihai Căpîlna and Mihai Emil Căpîlna

Cancers 2022, 14(9), 2346; https://doi.org/10.3390/cancers14092346 - 09 May 2022

Cited by 6 | Viewed by 2057

Abstract

Background: Considerable efforts have been carried out over the past 30 years to support patients with advanced cervical cancer. Throughout this time, Eastern European countries have been left aside from the decision-making groups on this matter, hence the absence of similar studies in [...] Read more.

Background: Considerable efforts have been carried out over the past 30 years to support patients with advanced cervical cancer. Throughout this time, Eastern European countries have been left aside from the decision-making groups on this matter, hence the absence of similar studies in this geographical area. In these countries, the quality of life (QoL) of patients with cervical cancer might be considered a “caprice”, and the discomforts they encounter following pelvic exenteration for cervical cancer are often perceived as a “normal phenomenon”. Methods: This study examined forty-seven patients submitted to pelvic exenteration followed up for nine years after the surgical intervention. The first objective of this study is to identify the prognostic factors that influence the overall survival (OS) of patients undergoing pelvic exenteration for FIGO stage IVA, recurrent or persistent cervical cancer after previous conclusive treatments. The second objective is to assess the QoL of the surviving patients using the QLQ-C30 and QLQ-CX24 standardized questionnaires. Results: The mean age of the participants was 54 years (range 36–67). At the time of the study, there were 25 living patients (53.2%), the 3-year OS was 61%, and the 5-year OS was 48.7%. Cox regression analysis recognized parameter invasion, pelvic lymph node metastases, positive resection margins, early postoperative complications, and infralevatorian pelvic exenteration as negative prognostic factors influencing the OS (p < 0.05). Of the 25 survivors, 18 patients answered the QoL questionnaires. The cost of favorable survival has been translated into poor overall QoL, unsatisfactory functional, social, and symptom scores, a high prevalence of cervical cancer-specific symptoms such as lymphedema, peripheral neuropathy, severe menopausal symptoms, distorted body image, and lack of sexual desire. The lower scores are comparable to the only three studies available in the literature that assessed the QoL of patients undergoing pelvic exenteration precisely for cervical cancer. Conclusions: Despite its retrospective nature and some limitations, this paper, similar to other studies, shows a decent OS but with a marked adverse impact on QoL, suggesting the importance of adequate psycho-emotional and financial support for these patients following pelvic exenteration. This study also contributes to the current knowledge regarding advanced cervical cancer treatment, depicting survival, prognostic factors, and QoL of patients undergoing pelvic exenteration for cervical cancer in a reference center in Eastern Europe. Our study can provide a comparison for future prospective randomized trials needed to confirm these results. Full article

(This article belongs to the Special Issue New Sights in Cancer Survival Analysis: Non-clinical Determinants of Survival for Patients with Cancer)

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13 pages, 710 KiB

Open AccessArticle

Surgical Implications of Advanced Low-Grade Serous Ovarian Cancer: Analysis of the Database of the Tumeurs Malignes Rares Gynécologiques Network

by Hélène Bonsang-Kitzis, Nabilah Panchbhaya, Anne-Sophie Bats, Eric Pujade-Lauraine, Patricia Pautier, Charlotte Ngô, Marie-Aude Le Frère-Belda, Elsa Kalbacher, Anne Floquet, Dominique Berton-Rigaud, Claudia Lefeuvre-Plesse, Michel Fabbro, Isabelle Ray-Coquard and Fabrice Lécuru

Cancers 2022, 14(9), 2345; https://doi.org/10.3390/cancers14092345 - 09 May 2022

Cited by 4 | Viewed by 3026

Abstract

The surgical specificities of advanced low-grade serous ovarian carcinoma (LGSOC) have been little investigated. Our objective was to describe surgical procedures/complications in primary (PDS) compared to interval debulking surgery (neoadjuvant chemotherapy and interval debulking surgery, NACT-IDS) and to assess the survival (progression-free (PFS) [...] Read more.

The surgical specificities of advanced low-grade serous ovarian carcinoma (LGSOC) have been little investigated. Our objective was to describe surgical procedures/complications in primary (PDS) compared to interval debulking surgery (neoadjuvant chemotherapy and interval debulking surgery, NACT-IDS) and to assess the survival (progression-free (PFS) and overall survival (OS)) in patients with advanced LGSOC. We retrospectively analyzed advanced LGSOC from a nationwide registry (January 2000 to July 2017). A total of 127 patients were included (48% PDS and 35% NACT-IDS). Peritoneal carcinomatosis was more severe (p = 0.01 to 0.0001, according to sites), surgery more complex (p = 0.03) and late postoperative morbidity more frequent (p = 0.03) and more severe in the NACT-IDS group. PFS and OS were similar in patients with CC0 and CC1 residual disease after PDS or IDS. Prognosis was poorest for NACT-IDS patients with CC2/CC3 resection (PFS: HR = 2.31, IC95% (1.3–4.58); p = 0.005; OS: HR = 4.98, IC95% (1.59–15.61); p = 0.006). NACT has no benefit in terms of surgical outputs in patients with advanced LGSOC. Patients with complete resection or minimal residual disease (CC0 and CC1) have similar prognoses. On the other hand, patients with CC2 and more residual disease have similar survival rates compared to nonoperated patients. Primary cytoreduction with complete or with minimal residuals should be preferred when feasible. Full article

(This article belongs to the Section Cancer Therapy)

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10 pages, 837 KiB

Open AccessArticle

Calcium Channel Blocker Use and the Risk for Breast Cancer: A Population-Based Nested Case-Control Study

by Victoria Rotshild, Bruria Hirsh Raccah, Muna Gazawe and Ilan Matok

Cancers 2022, 14(9), 2344; https://doi.org/10.3390/cancers14092344 - 09 May 2022

Cited by 8 | Viewed by 2182

Abstract

We investigated whether long-term exposure to calcium channel blockers (CCBs) is associated with an increased risk of breast cancer (BCa). We designed a nested case–control study based on data from the Clalit electronic database, the largest Israeli Health Services organization. All newly diagnosed [...] Read more.

We investigated whether long-term exposure to calcium channel blockers (CCBs) is associated with an increased risk of breast cancer (BCa). We designed a nested case–control study based on data from the Clalit electronic database, the largest Israeli Health Services organization. All newly diagnosed breast cancer (BCa) cases were selected from a cohort of patients with hypertension. Ten controls were matched for each BCa case. The odds ratios (ORs) of BCa among CCBs users were calculated using multivariate conditional logistic regression analyses. A total of 4875 patients with newly diagnosed BCa were identified from the cohort with a median follow-up of 5.15 years. The exposure to CCBs was not associated with an increased risk of BCa (OR = 0.98; 95% CI, 0.92–1.04). Additionally, there was no association between long-term exposure to CCBs (above eight years) and increased BCa risk (OR = 0.91; 95% CI, 0.67–1.21). Higher cumulative doses of CCBs were not associated with an elevated risk of BCa (OR = 0.997; 95% CI, 0.962–1.034, calculated per 1000 DDD). Based on this large population-based study, long-term exposure to CCBs was not associated with an increased risk of BCa. Considering that CCBs are widely used medications, our results provide important safety information on a population level, especially for patients with an increased risk of BCa. Full article

(This article belongs to the Collection Ion Channels in Cancer Therapies)

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12 pages, 1366 KiB

Open AccessReview

Lung Cancer Screening: New Perspective and Challenges in Europe

by Jan P. Van Meerbeeck, Emma O’Dowd, Brian Ward, Paul Van Schil and Annemiek Snoeckx

Cancers 2022, 14(9), 2343; https://doi.org/10.3390/cancers14092343 - 09 May 2022

Cited by 10 | Viewed by 2839

Abstract

Randomized-controlled trials have shown clear evidence that lung cancer screening with low-dose CT in a high-risk population of current or former smokers can significantly reduce lung-cancer-specific mortality by an inversion of stage distribution at diagnosis. This paper will review areas in which there [...] Read more.

Randomized-controlled trials have shown clear evidence that lung cancer screening with low-dose CT in a high-risk population of current or former smokers can significantly reduce lung-cancer-specific mortality by an inversion of stage distribution at diagnosis. This paper will review areas in which there is good or emerging evidence and areas which still require investment, research or represent implementation challenges. The implementation of population-based lung cancer screening in Europe is variable and fragmented. A number of European countries seem be on the verge of implementing lung cancer screening, mainly through the implementation of studies or trials. The cost and capacity of CT scanners and radiologists are considered to be the main hurdles for future implementation. Actions by the European Commission, related to its published Europe’s Beating Cancer Plan and the proposal to update recommendations on cancer screening, could be an incentive to help speed up its implementation. Full article

(This article belongs to the Special Issue Lung Adenocarcinoma: Screening and Surgical Treatment)

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16 pages, 2567 KiB

Open AccessArticle

Azacitidine vs. Decitabine in Unfit Newly Diagnosed Acute Myeloid Leukemia Patients: Results from the PETHEMA Registry

by Jorge Labrador, David Martínez-Cuadrón, Adolfo de la Fuente, Rebeca Rodríguez-Veiga, Josefina Serrano, Mar Tormo, Eduardo Rodriguez-Arboli, Fernando Ramos, Teresa Bernal, María López-Pavía, Fernanda Trigo, María Pilar Martínez-Sánchez, Juan-Ignacio Rodríguez-Gutiérrez, Carlos Rodríguez-Medina, Cristina Gil, Daniel García Belmonte, Susana Vives, María-Ángeles Foncillas, Manuel Pérez-Encinas, Andrés Novo, Isabel Recio, Gabriela Rodríguez-Macías, Juan Miguel Bergua, Víctor Noriega, Esperanza Lavilla, Alicia Roldán-Pérez, Miguel A. Sanz, Pau Montesinos and on behalf of PETHEMA Group Show full author list Hide full author list

Cancers 2022, 14(9), 2342; https://doi.org/10.3390/cancers14092342 - 09 May 2022

Cited by 4 | Viewed by 2721

Abstract

The hypomethylating agents, decitabine (DEC) and azacitidine (AZA), allowed more elderly acute myeloid leukemia (AML) patients to be treated. However, there are little direct comparative data on AZA and DEC. This multicenter retrospective study compared the outcomes of AZA and DEC in terms [...] Read more.

The hypomethylating agents, decitabine (DEC) and azacitidine (AZA), allowed more elderly acute myeloid leukemia (AML) patients to be treated. However, there are little direct comparative data on AZA and DEC. This multicenter retrospective study compared the outcomes of AZA and DEC in terms of response and overall survival (OS). Potential predictors associated with response and OS were also evaluated. A total of 626 AML patients were included (487 treated with AZA and 139 with DEC). Response rates were similar in both groups: CR was 18% with AZA vs. 23% with DEC (p = 0.20), CR/CRi was 20.5% vs. 25% (p = 0.27) and ORR was 32% vs. 39.5% (p = 0.12), respectively. Patients with leukocytes < 10 × 10⁹/L, bone marrow blasts < 50% and ECOG ≥ 2 had higher ORR with DEC than with AZA. OS was similar in both groups: 10.4 months (95% CI: 9.2–11.7) vs. 8.8 months (95% CI: 6.7–11.0, p = 0.455), for AZA and DEC, respectively. Age (≥80 years), leukocytes (≥ 10 × 10⁹/L), platelet count (<20 × 10⁹/L) and eGFR (≥45 mL/min/1.73 m²) were associated with higher OS with AZA compared to DEC. In conclusion, we found no differences in response and OS rates in AML patients treated with AZA or DEC. Full article

(This article belongs to the Collection Acute Myeloid Leukemia (AML))

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16 pages, 1996 KiB

Open AccessArticle

P-glycoprotein Mediates Resistance to the Anaplastic Lymphoma Kinase Inhibitor Ensartinib in Cancer Cells

by Chung-Pu Wu, Cheng-Yu Hung, Megumi Murakami, Yu-Shan Wu, Chun-Ling Lin, Yang-Hui Huang, Tai-Ho Hung, Jau-Song Yu and Suresh V. Ambudkar

Cancers 2022, 14(9), 2341; https://doi.org/10.3390/cancers14092341 - 09 May 2022

Cited by 7 | Viewed by 1952

Abstract

Ensartinib (X-396) is a promising second-generation small-molecule inhibitor of anaplastic lymphoma kinase (ALK) that was developed for the treatment of ALK-positive non-small-cell lung cancer. Preclinical and clinical trial results for ensartinib showed superior efficacy and a favorable safety profile compared to the first-generation [...] Read more.

Ensartinib (X-396) is a promising second-generation small-molecule inhibitor of anaplastic lymphoma kinase (ALK) that was developed for the treatment of ALK-positive non-small-cell lung cancer. Preclinical and clinical trial results for ensartinib showed superior efficacy and a favorable safety profile compared to the first-generation ALK inhibitors that have been approved by the U.S. Food and Drug Administration. Although the potential mechanisms of acquired resistance to ensartinib have not been reported, the inevitable emergence of resistance to ensartinib may limit its therapeutic application in cancer. In this work, we investigated the interaction of ensartinib with P-glycoprotein (P-gp) and ABCG2, two ATP-binding cassette (ABC) multidrug efflux transporters that are commonly associated with the development of multidrug resistance in cancer cells. Our results revealed that P-gp overexpression, but not expression of ABCG2, was associated with reduced cancer cell susceptibility to ensartinib. P-gp directly decreased the intracellular accumulation of ensartinib, and consequently reduced apoptosis and cytotoxicity induced by this drug. The cytotoxicity of ensartinib could be significantly reversed by treatment with the P-gp inhibitor tariquidar. In conclusion, we report that ensartinib is a substrate of P-gp, and provide evidence that this transporter plays a role in the development of ensartinib resistance. Further investigation is needed. Full article

(This article belongs to the Special Issue Mechanisms of Acquired Resistance to Targeted Therapy)

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14 pages, 4587 KiB

Open AccessArticle

Genome-Scale Metabolic Model Analysis of Metabolic Differences between Lauren Diffuse and Intestinal Subtypes in Gastric Cancer

by Seungyoon Nam and Yongmin Lee

Cancers 2022, 14(9), 2340; https://doi.org/10.3390/cancers14092340 - 09 May 2022

Cited by 3 | Viewed by 1945

Abstract

Gastric cancer (GC) is one of the most lethal cancers worldwide; it has a high mortality rate, particularly in East Asia. Recently, genetic events (e.g., mutations and copy number alterations) and molecular signaling associated with histologically different GC subtypes (diffuse and intestinal) have [...] Read more.

Gastric cancer (GC) is one of the most lethal cancers worldwide; it has a high mortality rate, particularly in East Asia. Recently, genetic events (e.g., mutations and copy number alterations) and molecular signaling associated with histologically different GC subtypes (diffuse and intestinal) have been elucidated. However, metabolic differences among the histological GC subtypes have not been studied systematically. In this study, we utilized transcriptome-based genome-scale metabolic models (GEMs) to identify differential metabolic pathways between Lauren diffuse and intestinal subtypes. We found that diverse metabolic pathways, including cholesterol homeostasis, xenobiotic metabolism, fatty acid metabolism, the MTORC1 pathway, and glycolysis, were dysregulated between the diffuse and intestinal subtypes. Our study provides an overview of the metabolic differences between the two subtypes, possibly leading to an understanding of metabolism in GC heterogeneity. Full article

(This article belongs to the Section Cancer Informatics and Big Data)

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23 pages, 1583 KiB

Open AccessReview

Regulation of NKG2D Stress Ligands and Its Relevance in Cancer Progression

by Amber B. Jones, Abbey Rocco, Lawrence S. Lamb, Gregory K. Friedman and Anita B. Hjelmeland

Cancers 2022, 14(9), 2339; https://doi.org/10.3390/cancers14092339 - 09 May 2022

Cited by 17 | Viewed by 4735

Abstract

Under cellular distress, multiple facets of normal homeostatic signaling are altered or disrupted. In the context of the immune landscape, external and internal stressors normally promote the expression of natural killer group 2 member D (NKG2D) ligands that allow for the targeted recognition [...] Read more.

Under cellular distress, multiple facets of normal homeostatic signaling are altered or disrupted. In the context of the immune landscape, external and internal stressors normally promote the expression of natural killer group 2 member D (NKG2D) ligands that allow for the targeted recognition and killing of cells by NKG2D receptor-bearing effector populations. The presence or absence of NKG2D ligands can heavily influence disease progression and impact the accessibility of immunotherapy options. In cancer, tumor cells are known to have distinct regulatory mechanisms for NKG2D ligands that are directly associated with tumor progression and maintenance. Therefore, understanding the regulation of NKG2D ligands in cancer will allow for targeted therapeutic endeavors aimed at exploiting the stress response pathway. In this review, we summarize the current understanding of regulatory mechanisms controlling the induction and repression of NKG2D ligands in cancer. Additionally, we highlight current therapeutic endeavors targeting NKG2D ligand expression and offer our perspective on considerations to further enhance the field of NKG2D ligand biology. Full article

(This article belongs to the Special Issue Advances in Immuno-Oncology Research)

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17 pages, 3726 KiB

Open AccessArticle

Oncopeptide MBOP Encoded by LINC01234 Promotes Colorectal Cancer through MAPK Signaling Pathway

by Chunyuan Tang, Ying Zhou, Wen Sun, Haihong Hu, Yuxi Liu, Lu Chen, Fengting Ou, Su Zeng, Nengming Lin and Lushan Yu

Cancers 2022, 14(9), 2338; https://doi.org/10.3390/cancers14092338 - 09 May 2022

Cited by 9 | Viewed by 2478

Abstract

Colorectal cancer (CRC) ranks third in incidence rate and second in mortality rate of malignancy worldwide, and the diagnosis and therapeutics of it remain to be further studied. With the emergence of noncoding RNAs (ncRNAs) and potential peptides derived from ncRNAs across various [...] Read more.

Colorectal cancer (CRC) ranks third in incidence rate and second in mortality rate of malignancy worldwide, and the diagnosis and therapeutics of it remain to be further studied. With the emergence of noncoding RNAs (ncRNAs) and potential peptides derived from ncRNAs across various biological processes, we here aimed to identify a ncRNA-derived peptide possible for revealing the oncogenesis of CRC. Through combined predictive analysis of the coding potential of a batch of long noncoding RNAs (lncRNAs), the existence of an 85 amino-acid-peptide, named MEK1-binding oncopeptide (MBOP) and encoded from LINC01234 was confirmed. Mass spectrometry and Western blot assays indicated the overexpression of MBOP in CRC tissues and cell lines compared to adjacent noncancerous tissues and the normal colonic epithelial cell line. In vivo and in vitro migration and proliferation assays defined MBOP as an oncogenic peptide. Immunoprecipitation trials showed that MEK1 was the key interacting protein of MBOP, and MBOP promoted the MEK1/pERK/MMP2/MMP9 axis in CRC. Two E3-ligase enzymes MAEA and RMND5A mediated the ubiquitin–protease-system-related degradation of MBOP. This study indicates that MBOP might be a candidate prognostic indicator and a potential target for clinical therapy of CRC. Full article

(This article belongs to the Topic Cancer Cell Metabolism)

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26 pages, 6441 KiB

Open AccessArticle

Impact of Secretion-Active Osteoblast-Specific Factor 2 in Promoting Progression and Metastasis of Head and Neck Cancer

by Désirée Gül, Andrea Schweitzer, Aya Khamis, Shirley K. Knauer, Guo-Bin Ding, Laura Freudelsperger, Ioannis Karampinis, Sebastian Strieth, Jan Hagemann and Roland H. Stauber

Cancers 2022, 14(9), 2337; https://doi.org/10.3390/cancers14092337 - 09 May 2022

Cited by 4 | Viewed by 2075

Abstract

Treatment success of head and neck cancer (HNC) is still hampered by tumor relapse due to metastases. Our study aimed to identify biomarkers by exploiting transcriptomics profiles of patient-matched metastases, primary tumors, and normal tissue mucosa as well as the TCGA HNC cohort [...] Read more.

Treatment success of head and neck cancer (HNC) is still hampered by tumor relapse due to metastases. Our study aimed to identify biomarkers by exploiting transcriptomics profiles of patient-matched metastases, primary tumors, and normal tissue mucosa as well as the TCGA HNC cohort data sets. Analyses identified osteoblast-specific factor 2 (OSF-2) as significantly overexpressed in lymph node metastases and primary tumors compared to normal tissue. High OSF-2 levels correlate with metastatic disease and reduced overall survival of predominantly HPV-negative HNC patients. No significant correlation was observed with tumor localization or therapy response. These findings were supported by the fact that OSF-2 expression was not elevated in cisplatin-resistant HNC cell lines. OSF-2 was strongly expressed in tumor-associated fibroblasts, suggesting a tumor microenvironment-promoting function. Molecular cloning and expression studies of OSF-2 variants from patients identified an evolutionary conserved bona fide protein secretion signal (¹MIPFLPMFSLLLLLIVNPINA²¹). OSF-2 enhanced cell migration and cellular survival under stress conditions, which could be mimicked by the extracellular administration of recombinant protein. Here, OSF-2 executes its functions via ß1 integrin, resulting in the phosphorylation of PI3K and activation of the Akt/PKB signaling pathway. Collectively, we suggest OSF-2 as a potential prognostic biomarker and drug target, promoting metastases by supporting the tumor microenvironment and lymph node metastases survival rather than by enhancing primary tumor proliferation or therapy resistance. Full article

(This article belongs to the Special Issue From Progression to Metastasis of Solid Cancer)

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19 pages, 6389 KiB

Open AccessArticle

Ephrin B Activate Src Family Kinases in Fibroblasts Inducing Stromal Remodeling in Prostate Cancer

by Mamatha Kakarla, Sathyavathi ChallaSivaKanaka, Mary F. Dufficy, Victoria Gil, Yana Filipovich, Renee Vickman, Susan E. Crawford, Simon W. Hayward and Omar E. Franco

Cancers 2022, 14(9), 2336; https://doi.org/10.3390/cancers14092336 - 09 May 2022

Cited by 7 | Viewed by 2638

Abstract

Through stromal-epithelial interactions, carcinoma associated fibroblasts (CAF) play a critical role in tumor growth and progression. Activation of erythrophoyetin-producing human hepatocellular (Eph) receptors has been implicated in cancer. Eph receptor interactions with Ephrin ligands lead to bidirectional signals in the recipient and effector [...] Read more.

Through stromal-epithelial interactions, carcinoma associated fibroblasts (CAF) play a critical role in tumor growth and progression. Activation of erythrophoyetin-producing human hepatocellular (Eph) receptors has been implicated in cancer. Eph receptor interactions with Ephrin ligands lead to bidirectional signals in the recipient and effector cells. The consequences of continuous reverse Ephrin signaling activation in fibroblasts on prostate cancer (PCa) is unknown. When compared to benign prostate fibroblast, CAF displayed higher expression of Ephrin B1, B2, and B3 ligands (EFNB1, EFNB2, and EFNB3). In this study, we found that continuous activation of EFNB1 and EFNB3 in a benign human prostate stromal cell line (BHPrS1) increased the expression of CAF markers and induced a CAF phenotype. BHPrS1^EFNB1 and BHPrS1^EFNB3 displayed a pro-tumorigenic secretome with multiple effects on neovascularization, collagen deposition, and cancer cell proliferation, overall increasing tumorigenicity of a premalignant prostate epithelial cell line BPH1 and PCa cell line LNCaP, both in vitro and in vivo. Inhibition of Src family kinases (SFK) in BHPrS1^EFNB1 and BHPrS1^EFNB3 suppressed EFNB-induced ɑ-SMA (Alpha-smooth muscle actin) and TN-C (Tenascin-C) in vitro. Our study suggests that acquisition of CAF characteristics via SFK activation in response to increased EFNB ligands could promote carcinogenesis via modulation of TME in PCa. Full article

(This article belongs to the Special Issue Stromal-Epithelial Interactions in Cancer Progression and Therapy Response)

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21 pages, 1112 KiB

Open AccessArticle

Analysis of Selected Nutritional Parameters in Patients with HPV-Related and Non-HPV-Related Oropharyngeal Cancer before and after Radiotherapy Alone or Combined with Chemotherapy

by Adam Brewczyński, Beata Jabłońska, Agnieszka Maria Mazurek, Jolanta Mrochem-Kwarciak, Sławomir Mrowiec, Mirosław Śnietura, Marek Kentnowski, Anna Kotylak, Zofia Kołosza, Krzysztof Składowski and Tomasz Rutkowski

Cancers 2022, 14(9), 2335; https://doi.org/10.3390/cancers14092335 - 09 May 2022

Viewed by 1735

Abstract

Background: Radiotherapy plays an essential role in the treatment of oropharyngeal carcinoma (OPC). The aim of this study was to assess and compare the nutritional status (NS) of patients with HPV-related (HPV+) and non-HPV-related (HPV-) OPC before and after radiotherapy (RT) or chemoradiotherapy [...] Read more.

Background: Radiotherapy plays an essential role in the treatment of oropharyngeal carcinoma (OPC). The aim of this study was to assess and compare the nutritional status (NS) of patients with HPV-related (HPV+) and non-HPV-related (HPV-) OPC before and after radiotherapy (RT) or chemoradiotherapy (CRT). Methods: The analysis included 127 patients with OPC who underwent radiotherapy (RT) alone, or in combination with chemotherapy (CRT), in the I Radiation and Clinical Oncology Department of Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, Poland. Patients were divided according to HPV status. Confirmation of HPV etiology was obtained from FFPE (formalin-fixed, paraffin-embedded) tissue material and/or extracellular circulating HPV DNA. Basic anthropometric and biochemical parameters before and after RT/CRT were compared between the HPV- and HPV+ groups. The effect of NS on survival was also analyzed. Results: In both groups, a significant decrease in all analyzed nutritional parameters was noted after RT/CRT (p < 0.01). CRT caused significant weight loss and decreases in BMI, albumin, total lymphocyte count (TLC), and hemoglobin concentration, as well as an increase in the Nutritional Risk Score (NRS) 2002, in HPV- and HPV+ patients. A significant decrease in prealbumin levels after CRT was noted only in HPV+ patients. RT caused a significant decrease in hemoglobin concentration and TLC in HPV- patients. There were no significant differences regarding other nutritional parameters after RT in either group. RT did not have negative impact on body mass index (BMI), weight, NRS, CRP, Alb, Prealb, or PNI. Overall survival (OS) and disease-free survival (DFS) were significantly better in patients with a higher BMI in the HPV- group (OS, p = 0.011; DFS, p = 0.028); DFS was significantly better in patients with C-reactive protein (CRP) < 3.5 g/dL in the HPV- (p = 0.021) and HPV+ (p = 0.018) groups, and with total lymphocyte count (TLC) >1.28/mm³ in the HPV+ group (p = 0.014). Higher NRS 2002 was an independent adverse prognostic factor for OS and DFS in HPV-, but not in the HPV+ group. Kaplan–Meier analysis showed that both OS and DFS were significantly better in HPV- patients with lower NRS 2002 scores. However, this relationship was not observed in the HPV+ group. Conclusions: Regardless of HPV status, patients with OPC can develop malnutrition during RT/CRT. Therefore, nutritional support during RT/CRT is required in patients with HPV- and HPV+ OPC. Full article

(This article belongs to the Special Issue Diagnostic, Prognostic, Predictive Biomarkers and New Targets for Treatment in Head and Neck Cancers)

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15 pages, 2284 KiB

Open AccessArticle

Can We Reboot the Role of Intraperitoneal Chemotherapy in the Treatment for Gastric Cancer with Peritoneal Carcinomatosis?: A Retrospective Cohort Study Regarding Minimally Invasive Surgery Conjoined with Intraperitoneal plus Systemic Chemotherapy

by Sungho Kim, Chang-Min Lee, Danbi Lee, Jong-Han Kim, Sungsoo Park and Seong-Heum Park

Cancers 2022, 14(9), 2334; https://doi.org/10.3390/cancers14092334 - 09 May 2022

Cited by 1 | Viewed by 1862

Abstract

Background: Peritoneal carcinomatosis (PC) is the most common form of metastasis in gastric cancer (GC) and is related with a poor prognosis. Several treatment modalities including systemic chemotherapy and intraperitoneal chemotherapy have been studied and adopted in treatment of GC patients with PC. [...] Read more.

Background: Peritoneal carcinomatosis (PC) is the most common form of metastasis in gastric cancer (GC) and is related with a poor prognosis. Several treatment modalities including systemic chemotherapy and intraperitoneal chemotherapy have been studied and adopted in treatment of GC patients with PC. Nevertheless, few studies have reported the comparison of the oncologic outcomes between minimally invasive surgery (MIS) with intraperitoneal (IP) chemotherapy and conventional chemotherapy for GC with PC. Methods: We retrospectively reviewed the clinical records of 74 patients who had been diagnosed as GC with PC via either intra-abdominal exploration or abdominopelvic computed tomography between January 2011 and April 2021. After performing propensity score-matching for this retrospective data, we compared the outcomes of 26 patients who underwent MIS followed by IP combined systemic chemotherapy (MIS-IP group) and 26 patients who underwent systemic chemotherapy only (SC-only group). Results: The 2-year progression free survival rate of the MIS-IP group was significantly higher than the SC-only groups (36.4% and 10.5%, respectively; p = 0.010). In multivariate analysis to detect relevant factors on PFS, IP chemotherapy (HR 0.213; p < 0.001), Eastern Cooperative Oncology Group performance status (HR 3.689; p = 0.002), and the amount of ascites (p = 0.011) were significant prognostic factors. Conclusions: This study demonstrated the therapeutic potential of MIS conjoined IP plus systemic chemotherapy for GC patients with PC. MIS conjoined by IP plus systemic chemotherapy can be adopted as a treatment option to reboot the role of IP chemotherapy in GC patients with PC. Full article

(This article belongs to the Special Issue Advanced Gastric Cancer)

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24 pages, 1110 KiB

Open AccessReview

Regulation of Carcinogenesis by Sensory Neurons and Neuromediators

by Nuray Erin, Galina V. Shurin, James H. Baraldi and Michael R. Shurin

Cancers 2022, 14(9), 2333; https://doi.org/10.3390/cancers14092333 - 09 May 2022

Cited by 12 | Viewed by 3870

Abstract

Interactions between the immune system and the nervous system are crucial in maintaining homeostasis, and disturbances of these neuro-immune interactions may participate in carcinogenesis and metastasis. Nerve endings have been identified within solid tumors in humans and experimental animals. Although the involvement of [...] Read more.

Interactions between the immune system and the nervous system are crucial in maintaining homeostasis, and disturbances of these neuro-immune interactions may participate in carcinogenesis and metastasis. Nerve endings have been identified within solid tumors in humans and experimental animals. Although the involvement of the efferent sympathetic and parasympathetic innervation in carcinogenesis has been extensively investigated, the role of the afferent sensory neurons and the neuropeptides in tumor development, growth, and progression is recently appreciated. Similarly, current findings point to the significant role of Schwann cells as part of neuro-immune interactions. Hence, in this review, we mainly focus on local and systemic effects of sensory nerve activity as well as Schwann cells in carcinogenesis and metastasis. Specific denervation of vagal sensory nerve fibers, or vagotomy, in animal models, has been reported to markedly increase lung metastases of breast carcinoma as well as pancreatic and gastric tumor growth, with the formation of liver metastases demonstrating the protective role of vagal sensory fibers against cancer. Clinical studies have revealed that patients with gastric ulcers who have undergone a vagotomy have a greater risk of stomach, colorectal, biliary tract, and lung cancers. Protective effects of vagal activity have also been documented by epidemiological studies demonstrating that high vagal activity predicts longer survival rates in patients with colon, non-small cell lung, prostate, and breast cancers. However, several studies have reported that inhibition of sensory neuronal activity reduces the development of solid tumors, including prostate, gastric, pancreatic, head and neck, cervical, ovarian, and skin cancers. These contradictory findings are likely to be due to the post-nerve injury-induced activation of systemic sensory fibers, the level of aggressiveness of the tumor model used, and the local heterogeneity of sensory fibers. As the aggressiveness of the tumor model and the level of the inflammatory response increase, the protective role of sensory nerve fibers is apparent and might be mostly due to systemic alterations in the neuro-immune response. Hence, more insights into inductive and permissive mechanisms, such as systemic, cellular neuro-immunological mechanisms of carcinogenesis and metastasis formation, are needed to understand the role of sensory neurons in tumor growth and spread. Full article

(This article belongs to the Special Issue The Tumor Neuroenvironment)

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12 pages, 901 KiB

Open AccessArticle

Impact of Individual Comorbidities on Survival of Patients with Myelofibrosis

by María García-Fortes, Juan C. Hernández-Boluda, Alberto Álvarez-Larrán, José M. Raya, Anna Angona, Natalia Estrada, Laura Fox, Beatriz Cuevas, María C. García-Hernández, María Teresa Gómez-Casares, Francisca Ferrer-Marín, Silvana Saavedra, Francisco Cervantes, Regina García-Delgado and on behalf of the Grupo Español de Enfermedades Mieloproliferativas Filadelfia Negativas (GEMFIN)

Cancers 2022, 14(9), 2331; https://doi.org/10.3390/cancers14092331 - 09 May 2022

Cited by 2 | Viewed by 2020

Abstract

The comorbidity burden is an important risk factor for overall survival (OS) in several hematological malignancies. This observational prospective study was conducted to evaluate the impact of individual comorbidities on survival in a multicenter series of 668 patients with primary myelofibrosis (PMF) or [...] Read more.

The comorbidity burden is an important risk factor for overall survival (OS) in several hematological malignancies. This observational prospective study was conducted to evaluate the impact of individual comorbidities on survival in a multicenter series of 668 patients with primary myelofibrosis (PMF) or MF secondary to polycythemia vera (PPV-MF) or essential thrombocythemia (PET-MF). Hypertension (hazard ratio (HR) = 4.96, p < 0.001), smoking (HR = 5.08, p < 0.001), dyslipidemia (HR = 4.65, p < 0.001) and hepatitis C virus (HCV) (HR = 4.26, p = 0.015) were most adversely associated with OS. Diabetes (HR = 3.01, p < 0.001), pulmonary disease (HR = 3.13, p < 0.001) and renal dysfunction (HR = 1.82, p = 0.037) were also associated with an increased risk of death. Multivariate analysis showed that pulmonary disease (HR = 2.69, p = 0.001), smoking (HR = 3.34, p < 0.001), renal dysfunction (HR = 2.08, p = 0.043) and HCV (HR = 11.49, p = 0.001) had a negative impact on OS. When ruxolitinib exposure was included in the model, the effect of each comorbidity on survival was modified. Therefore, individual comorbidities should be taken into account in determining the survival prognosis for patients with MF. Full article

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23 pages, 538 KiB

Open AccessReview

Peripheral T-Cell Lymphomas: Therapeutic Approaches

by David Sibon

Cancers 2022, 14(9), 2332; https://doi.org/10.3390/cancers14092332 - 08 May 2022

Cited by 5 | Viewed by 2908

Abstract

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of rare neoplasms of mature T cells or natural killer (NK) cell. PTCLs usually have an aggressive course and a poor outcome. In recent years, significant progress has been made in the knowledge of the [...] Read more.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of rare neoplasms of mature T cells or natural killer (NK) cell. PTCLs usually have an aggressive course and a poor outcome. In recent years, significant progress has been made in the knowledge of the molecular lymphomagenesis of PTCLs, and through the development of new, more specific therapeutic molecules, one can hope in the coming years for more personalized medicine and improved patient prognosis. This review aims to provide an up-to-date overview of the current therapeutic approaches in nodal PTCLs. Full article

(This article belongs to the Special Issue T-Cell Lymphomas)

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14 pages, 609 KiB

Open AccessArticle

Return to Work, Fatigue and Cancer Rehabilitation after Curative Radiotherapy and Radiochemotherapy for Pelvic Gynecologic Cancer

by Eva Meixner, Elisabetta Sandrini, Line Hoeltgen, Tanja Eichkorn, Philipp Hoegen, Laila König, Nathalie Arians, Jonathan W. Lischalk, Markus Wallwiener, Ilse Weis, Daniela Roob, Jürgen Debus and Juliane Hörner-Rieber

Cancers 2022, 14(9), 2330; https://doi.org/10.3390/cancers14092330 - 08 May 2022

Cited by 3 | Viewed by 2274

Abstract

Pain, fatigue, and depression are a common cluster of symptoms among cancer patients that impair quality of life and daily activities. We aimed to evaluate the burden of cancer rehabilitation and return-to-work (RTW) rates. Tumor characteristics, lifestyle and household details, treatment data, the [...] Read more.

Pain, fatigue, and depression are a common cluster of symptoms among cancer patients that impair quality of life and daily activities. We aimed to evaluate the burden of cancer rehabilitation and return-to-work (RTW) rates. Tumor characteristics, lifestyle and household details, treatment data, the use of in-house social services and post-treatment inpatient rehabilitation, and RTW were assessed for 424 women, diagnosed with cervical, uterine, or vaginal/vulvar cancer, receiving curative radio(chemo)therapy. Progression-free RTW rate at 3 months was 32.3%, and increased to 58.1% and 63.2% at 12 and 18 months, respectively. Patients with advanced FIGO stages and intensified treatments significantly suffered more from acute pain and fatigue. A higher Charlson-Comorbidity-Index reliably predicted patients associated with a higher risk of acute fatigue during RT. Aside from the presence of children, no other household or lifestyle factor was correlated with increased fatigue rates. Women aged ≤ 45 years had a significantly higher risk of developing depression requiring treatment during follow-up. Post-treatment inpatient cancer rehabilitation, including exercise and nutrition counseling, significantly relieved fatigue symptoms. The burdens for recovery from cancer therapy remain multi-factorial. Special focus needs to be placed on identifying high-risk groups experiencing fatigue or pain. Specialized post-treatment inpatient cancer rehabilitation can improve RTW rates. Full article

(This article belongs to the Collection Quality of Life in Cancer Rehabilitation)

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16 pages, 1293 KiB

Open AccessArticle

Impaired Global Longitudinal Strain Is Associated with Cardiovascular Events in Hodgkin Lymphoma Survivors

by Elissa A. S. Polomski, Julius C. Heemelaar, Augustinus D. G. Krol, Marloes Louwerens, Saskia L. M. A. Beeres, Eduard R. Holman, J. Wouter Jukema, Martin J. Schalij and M. Louisa Antoni

Cancers 2022, 14(9), 2329; https://doi.org/10.3390/cancers14092329 - 08 May 2022

Viewed by 2171

Abstract

Background: Treatment with thoracic irradiation for classic Hodgkin lymphoma (CHL) leads to improved survival but also increases the risk of cardiovascular events. Left ventricular (LV) dysfunction is usually assessed by echocardiographic left ventricular ejection fraction (LVEF), whereas global longitudinal strain (GLS) can detect [...] Read more.

Background: Treatment with thoracic irradiation for classic Hodgkin lymphoma (CHL) leads to improved survival but also increases the risk of cardiovascular events. Left ventricular (LV) dysfunction is usually assessed by echocardiographic left ventricular ejection fraction (LVEF), whereas global longitudinal strain (GLS) can detect early subclinical LV dysfunction. The purpose of this study was to evaluate if conventional echocardiographic parameters and GLS are associated with cardiovascular events during long-term follow-up. Methods: 161 consecutive CHL patients treated with radiotherapy who underwent echocardiography > 10 years after diagnosis were assessed for eligibility. Multivariable cause-specific Cox regression was performed for a composite outcome of cardiac death and cardiovascular events and the competing outcome of noncardiac death. Results: 129 patients (61.2% female, N = 79) with a mean age of 46.3 ± 11.0 years at index visit were eligible for analysis. GLS was impaired in 51 patients (39.5%) and 10.9% had a LVEF of< 50%. The median E/e’ was 9.2 [7.2;12.7]. Adjusted for confounders, GLS > −16% showed a significant association with a near four-fold risk of the composite endpoint (HR = 3.95, 95% CI: 1.83–8.52, p < 0.001). LVEF < 50% (HR = 2.99, p = 0.016) and E/e’ (HR = 1.16, p < 0.001) also showed a significant relationship with the outcome. None of the aforementioned parameters were associated with the competing outcome. Conclusions: This study shows that LV dysfunction including impaired GLS in CHL survivors is associated with cardiovascular events and cardiac death. Full article

(This article belongs to the Special Issue Novel Markers in Lymphoma)

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10 pages, 527 KiB

Open AccessArticle

Correlation between Colon Perfusion and Postoperative Fecal Output through a Transanal Drainage Tube during Laparoscopic Low Anterior Resection

by Kenji Kawada, Toshiaki Wada, Takehito Yamamoto, Yoshiro Itatani, Koya Hida and Kazutaka Obama

Cancers 2022, 14(9), 2328; https://doi.org/10.3390/cancers14092328 - 08 May 2022

Cited by 1 | Viewed by 1733

Abstract

In order to prevent anastomotic leakage (AL) following rectal surgery, various solutions—such as intraoperative indocyanine green (ICG) angiography and transanal drainage tubes (TDT)—have been proposed. This study investigated the relationship between intestinal perfusion and fecal volume through TDT in laparoscopic low anterior resection [...] Read more.

In order to prevent anastomotic leakage (AL) following rectal surgery, various solutions—such as intraoperative indocyanine green (ICG) angiography and transanal drainage tubes (TDT)—have been proposed. This study investigated the relationship between intestinal perfusion and fecal volume through TDT in laparoscopic low anterior resection (LAR). A total of 59 rectal cancer patients who underwent laparoscopic LAR with both intraoperative ICG angiography and postoperative TDT placement were retrospectively analyzed. The relationship between intestinal perfusion and fecal volume through TDT was examined. Based on the ICG fluorescence, the transection site was shifted more proximally in 20 cases (33.9%). Symptomatic AL occurred in seven patients (11.8%). The AL rate of the patients whose daily fecal volume exceeded 100 mL/day in 2 or more days was significantly higher than that of those whose daily fecal volume exceeded it in 0 or 1 day (44.4% vs. 6.0%; p < 0.01). Univariate and multivariate analyses showed that the need for a proximal shift of the transection site was significantly associated with a high fecal volume. The quantitative analysis of ICG fluorescence indicated that Fmax (the fluorescence difference between the baseline and maximum) was significantly associated with fecal volume through TDT. Full article

(This article belongs to the Special Issue Biophotonics and Imaging for Cancer Screening, Diagnosis and Treatment Monitoring)

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24 pages, 4303 KiB

Open AccessArticle

Upregulation of the Mevalonate Pathway through EWSR1-FLI1/EGR2 Regulatory Axis Confers Ewing Cells Exquisite Sensitivity to Statins

by Charlie Buchou, Karine Laud-Duval, Wietske van der Ent, Sandrine Grossetête, Sakina Zaidi, Géraldine Gentric, Maxime Corbé, Kévin Müller, Elaine Del Nery, Didier Surdez and Olivier Delattre

Cancers 2022, 14(9), 2327; https://doi.org/10.3390/cancers14092327 - 08 May 2022

Cited by 6 | Viewed by 2474

Abstract

Ewing sarcoma (EwS) is an aggressive primary bone cancer in children and young adults characterized by oncogenic fusions between genes encoding FET-RNA-binding proteins and ETS transcription factors, the most frequent fusion being EWSR1-FLI1. We show that EGR2, an Ewing-susceptibility gene and an essential [...] Read more.

Ewing sarcoma (EwS) is an aggressive primary bone cancer in children and young adults characterized by oncogenic fusions between genes encoding FET-RNA-binding proteins and ETS transcription factors, the most frequent fusion being EWSR1-FLI1. We show that EGR2, an Ewing-susceptibility gene and an essential direct target of EWSR1-FLI1, directly regulates the transcription of genes encoding key enzymes of the mevalonate (MVA) pathway. Consequently, Ewing sarcoma is one of the tumors that expresses the highest levels of mevalonate pathway genes. Moreover, genome-wide screens indicate that MVA pathway genes constitute major dependencies of Ewing cells. Accordingly, the statin inhibitors of HMG-CoA-reductase, a rate-limiting enzyme of the MVA pathway, demonstrate cytotoxicity in EwS. Statins induce increased ROS and lipid peroxidation levels, as well as decreased membrane localization of prenylated proteins, such as small GTP proteins. These metabolic effects lead to an alteration in the dynamics of S-phase progression and to apoptosis. Statin-induced effects can be rescued by downstream products of the MVA pathway. Finally, we further show that statins impair tumor growth in different Ewing PDX models. Altogether, the data show that statins, which are off-patent, well-tolerated, and inexpensive compounds, should be strongly considered in the therapeutic arsenal against this deadly childhood disease. Full article

(This article belongs to the Special Issue Targeted Therapies for Pediatric Solid Tumors)

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18 pages, 829 KiB

Open AccessReview

Patients with Positive Lymph Nodes after Radical Prostatectomy and Pelvic Lymphadenectomy—Do We Know the Proper Way of Management?

by Bartosz Małkiewicz, Miłosz Knura, Małgorzata Łątkowska, Maximilian Kobylański, Krystian Nagi, Dawid Janczak, Joanna Chorbińska, Wojciech Krajewski, Jakub Karwacki and Tomasz Szydełko

Cancers 2022, 14(9), 2326; https://doi.org/10.3390/cancers14092326 - 08 May 2022

Cited by 3 | Viewed by 4905

Abstract

Lymph node invasion in prostate cancer is a significant prognostic factor indicating worse prognosis. While it significantly affects both survival rates and recurrence, proper management remains a controversial and unsolved issue. The thorough evaluation of risk factors associated with nodal involvement, such as [...] Read more.

Lymph node invasion in prostate cancer is a significant prognostic factor indicating worse prognosis. While it significantly affects both survival rates and recurrence, proper management remains a controversial and unsolved issue. The thorough evaluation of risk factors associated with nodal involvement, such as lymph node density or extracapsular extension, is crucial to establish the potential expansion of the disease and to substratify patients clinically. There are multiple strategies that may be employed for patients with positive lymph nodes. Nowadays, therapeutic methods are generally based on observation, radiotherapy, and androgen deprivation therapy. However, the current guidelines are incoherent in terms of the most effective management approach. Future management strategies are expected to make use of novel diagnostic tools and therapies, such as photodynamic therapy or diagnostic imaging with prostate-specific membrane antigen. Nevertheless, this heterogeneous group of men remains a great therapeutic concern, and both the clarification of the guidelines and the optimal substratification of patients are required. Full article

(This article belongs to the Special Issue Prostate Cancer Therapy)

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24 pages, 1189 KiB

Open AccessArticle

A Data Science Approach for the Identification of Molecular Signatures of Aggressive Cancers

by Adriano Barbosa-Silva, Milena Magalhães, Gilberto Ferreira Da Silva, Fabricio Alves Barbosa Da Silva, Flávia Raquel Gonçalves Carneiro and Nicolas Carels

Cancers 2022, 14(9), 2325; https://doi.org/10.3390/cancers14092325 - 07 May 2022

Cited by 3 | Viewed by 3637

Abstract

The main hallmarks of cancer include sustaining proliferative signaling and resisting cell death. We analyzed the genes of the WNT pathway and seven cross-linked pathways that may explain the differences in aggressiveness among cancer types. We divided six cancer types (liver, lung, stomach, [...] Read more.

The main hallmarks of cancer include sustaining proliferative signaling and resisting cell death. We analyzed the genes of the WNT pathway and seven cross-linked pathways that may explain the differences in aggressiveness among cancer types. We divided six cancer types (liver, lung, stomach, kidney, prostate, and thyroid) into classes of high (H) and low (L) aggressiveness considering the TCGA data, and their correlations between Shannon entropy and 5-year overall survival (OS). Then, we used principal component analysis (PCA), a random forest classifier (RFC), and protein–protein interactions (PPI) to find the genes that correlated with aggressiveness. Using PCA, we found GRB2, CTNNB1, SKP1, CSNK2A1, PRKDC, HDAC1, YWHAZ, YWHAB, and PSMD2. Except for PSMD2, the RFC analysis showed a different list, which was CAD, PSMD14, APH1A, PSMD2, SHC1, TMEFF2, PSMD11, H2AFZ, PSMB5, and NOTCH1. Both methods use different algorithmic approaches and have different purposes, which explains the discrepancy between the two gene lists. The key genes of aggressiveness found by PCA were those that maximized the separation of H and L classes according to its third component, which represented 19% of the total variance. By contrast, RFC classified whether the RNA-seq of a tumor sample was of the H or L type. Interestingly, PPIs showed that the genes of PCA and RFC lists were connected neighbors in the PPI signaling network of WNT and cross-linked pathways. Full article

(This article belongs to the Topic Big Data in Healthcare, Bioinformatics and Precision Medicine)

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27 pages, 726 KiB

Open AccessReview

Sinonasal Side Effects of Chemotherapy and/or Radiation Therapy for Head and Neck Cancer: A Literature Review

by Giuseppe Riva, Ester Cravero, Claudia Pizzo, Marco Briguglio, Giuseppe Carlo Iorio, Chiara Cavallin, Oliviero Ostellino, Mario Airoldi, Umberto Ricardi and Giancarlo Pecorari

Cancers 2022, 14(9), 2324; https://doi.org/10.3390/cancers14092324 - 07 May 2022

Cited by 13 | Viewed by 2479

Abstract

Radiotherapy and chemotherapy represent important treatment modalities for head and neck cancer. Rhinosinusitis and smell alterations are common side effects in the sinonasal region. This review will summarize and analyze our current knowledge of the sinonasal side effects of chemotherapy and/or radiation therapy [...] Read more.

Radiotherapy and chemotherapy represent important treatment modalities for head and neck cancer. Rhinosinusitis and smell alterations are common side effects in the sinonasal region. This review will summarize and analyze our current knowledge of the sinonasal side effects of chemotherapy and/or radiation therapy for head and neck cancer (HNC), with a specific focus on mucosal and olfactory disorders. A review of the English literature was performed using several databases (PubMed, Embase, Cochrane, Scopus). Fifty-six articles were included in qualitative synthesis: 28 assessed mucosal disorders (rhinitis or rhinosinusitis), 26 evaluated olfactory alterations, and 2 articles addressed both topics. The incidence and severity of olfactory dysfunction and chronic rhinosinusitis were highest at the end of radiotherapy and at three months after treatment and decreased gradually over time. Smell acuity deterioration and chronic rhinosinusitis seemed to be related to radiation dose on olfactory area and nasal cavities, but different degrees of recovery were observed. In conclusion, it is important to establish the severity of chronic rhinosinusitis and olfactory dysfunction in order to find strategies to support patients and improve their quality of life. Full article

(This article belongs to the Special Issue Multimodality and Sequential Therapy in Locally Advanced Head and Neck Cancer)

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15 pages, 1074 KiB

Open AccessSystematic Review

Recurrence of Uterine Smooth Muscle Tumor of Uncertain Malignant Potential: A Systematic Review of the Literature

by Jacopo Di Giuseppe, Camilla Grelloni, Lucia Giuliani, Giovanni Delli Carpini, Luca Giannella and Andrea Ciavattini

Cancers 2022, 14(9), 2323; https://doi.org/10.3390/cancers14092323 - 07 May 2022

Cited by 9 | Viewed by 2891

Abstract

Background: This study aimed to systematically review the existing literature on uterine smooth muscle tumor of uncertain malignant potential (STUMP) to provide information about characteristics and outcomes of patients and the risk factors for recurrence over a period of 60 years (1960–2021). [...] Read more.

Background: This study aimed to systematically review the existing literature on uterine smooth muscle tumor of uncertain malignant potential (STUMP) to provide information about characteristics and outcomes of patients and the risk factors for recurrence over a period of 60 years (1960–2021). Methods: According to PRISMA guidelines, we searched for "uterine smooth muscle tumor of uncertain malignant potential" in PubMed (all fields) and Scopus (Title/Abstract/Keywords) databases (accessed on 1 January 2022). Relevant articles were obtained in full-text format and screened for additional references. The only filter used was the English language. Studies including full case description of patients with histopathological diagnosis of STUMP in accordance with Stanford criteria were included. Results: Thirty-four studies, including 189 cases, were included. The median age was 43 years, and in 21.5% of cases there was a recurrence of the disease. Bivariate analysis showed a significant association between use of morcellation without bag and risk of recurrence (p = 0.001). Unprotected morcellation during demolitive or conservative surgery was independently associated with a higher risk of disease recurrence with a relative risk of 2.94 (p < 0.001). A significant progressive decrease in the recurrence rate was observed over time (r = −0.671, p = 0.008). The percentage of patients who underwent surgery followed by in-bag protected morcellation significantly increased after the publication of the U.S. Food and Drug Administration alert about the risk linked to this procedure (p = 0.01). Conclusions: Unprotected morcellation of the lesion is associated with the relapse of the disease. However, this clinical condition showed a drastic decrease over time. This could likely be due to the increased awareness by surgeons of the importance of customizing surgical treatment. Full article

(This article belongs to the Section Systematic Review or Meta-Analysis in Cancer Research)

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32 pages, 9747 KiB

Open AccessReview

Muscarinic Receptors Associated with Cancer

by Gloria M. Calaf, Leodan A. Crispin, Juan P. Muñoz, Francisco Aguayo and Tammy C. Bleak

Cancers 2022, 14(9), 2322; https://doi.org/10.3390/cancers14092322 - 07 May 2022

Cited by 7 | Viewed by 3131

Abstract

Cancer has been considered the pathology of the century and factors such as the environment may play an important etiological role. The ability of muscarinic agonists to stimulate growth and muscarinic receptor antagonists to inhibit tumor growth has been demonstrated for breast, melanoma, [...] Read more.

Cancer has been considered the pathology of the century and factors such as the environment may play an important etiological role. The ability of muscarinic agonists to stimulate growth and muscarinic receptor antagonists to inhibit tumor growth has been demonstrated for breast, melanoma, lung, gastric, colon, pancreatic, ovarian, prostate, and brain cancer. This work aimed to study the correlation between epidermal growth factor receptors and cholinergic muscarinic receptors, the survival differences adjusted by the stage clinical factor, and the association between gene expression and immune infiltration level in breast, lung, stomach, colon, liver, prostate, and glioblastoma human cancers. Thus, targeting cholinergic muscarinic receptors appears to be an attractive therapeutic alternative due to the complex signaling pathways involved. Full article

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32 pages, 4145 KiB

Open AccessReview

Current Pathology Model of Pancreatic Cancer

by Krzysztof Szymoński, Katarzyna Milian-Ciesielska, Ewelina Lipiec and Dariusz Adamek

Cancers 2022, 14(9), 2321; https://doi.org/10.3390/cancers14092321 - 07 May 2022

Cited by 8 | Viewed by 4437

Abstract

Pancreatic cancer (PC) is one of the most aggressive and lethal malignant neoplasms, ranking in seventh place in the world in terms of the incidence of death, with overall 5-year survival rates still below 10%. The knowledge about PC pathomechanisms is rapidly expanding. [...] Read more.

Pancreatic cancer (PC) is one of the most aggressive and lethal malignant neoplasms, ranking in seventh place in the world in terms of the incidence of death, with overall 5-year survival rates still below 10%. The knowledge about PC pathomechanisms is rapidly expanding. Daily reports reveal new aspects of tumor biology, including its molecular and morphological heterogeneity, explain complicated “cross-talk” that happens between the cancer cells and tumor stroma, or the nature of the PC-associated neural remodeling (PANR). Staying up-to-date is hard and crucial at the same time. In this review, we are focusing on a comprehensive summary of PC aspects that are important in pathologic reporting, impact patients’ outcomes, and bring meaningful information for clinicians. Finally, we show promising new trends in diagnostic technologies that might bring a difference in PC early diagnosis. Full article

(This article belongs to the Special Issue Advanced Pancreatic Cancer)

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12 pages, 957 KiB

Open AccessArticle

Cancer Therapy-Related Cardiac Dysfunction in Patients Treated with a Combination of an Immune Checkpoint Inhibitor and Doxorubicin

by Seon-Hwa Lee, Iksung Cho, Seng-Chan You, Min-Jae Cha, Jee-Suk Chang, William D. Kim, Kyu-yong Go, Dae-Young Kim, Jiwon Seo, Chi-Young Shim, Geu-Ru Hong, Seok-Min Kang, Jong-Won Ha, Sun-Young Rha and Hyo-Song Kim

Cancers 2022, 14(9), 2320; https://doi.org/10.3390/cancers14092320 - 07 May 2022

Cited by 3 | Viewed by 2075

Abstract

Backgrounds: There are scarce data on whether immune checkpoint inhibitors (ICIs) increase the risk of cardiac dysfunction when used with cardiotoxic agents. Thus, we evaluated cardiac dysfunction in patients with sarcoma receiving doxorubicin with or without ICI using echocardiography and left ventricular global [...] Read more.

Backgrounds: There are scarce data on whether immune checkpoint inhibitors (ICIs) increase the risk of cardiac dysfunction when used with cardiotoxic agents. Thus, we evaluated cardiac dysfunction in patients with sarcoma receiving doxorubicin with or without ICI using echocardiography and left ventricular global longitudinal strain (LVGLS). Methods: A total of 95 patients were included in this study. Echocardiography and LVGLS were evaluated at baseline and follow-up (at 3 and 6 months of chemotherapy) and compared with the doxorubicin (Dox; n = 73) and concomitant ICI with doxorubicin (Dox-ICI; n = 22) groups. Cancer therapy-related cardiac dysfunction (CTRCD) was defined as a left ventricular ejection fraction (LVEF) drop of >10% and LVEF of <50% (definite CTRCD), LVEF drop of >10%, LVEF of ≥50%, and LVGLS relative reduction of >15% (probable CTRCD) at six months. Results: There were no significant differences in age, cumulative dose of doxorubicin, and cardiovascular risk factors between the two groups. At baseline, the LVEF was similar in the Dox and Dox-ICI groups (p = 0.493). In the Dox group, LVEF decreased to 59 ± 6% (Δ −7 ± 1.3%, p < 0.001) and LVGLS decreased from −17.3 ± 3.2% to −15.4 ± 3.2% (Δ −10.1 ± −1.9%, p < 0.001) at six months. In the Dox-ICI group, LVEF decreased to 55 ± 9% (Δ −9 ± 2.1%, p < 0.001), along with a significant decrease in LVGLS (from −18.6 ± 1.9% to −15.3 ± 3.6%, Δ −12.4 ± −2.4%, p < 0.001). Over a median follow-up of 192 days, there were no cases with clinical manifestations of fulminant myocarditis. In the Dox group, definite and probable CTRCD were observed in seven (10.1%) and five (7.4%) patients, respectively. In the Dox-ICI group, definite and probable CTRCD were observed in four (19%) and four (19%) patients, respectively. The total number of patients who developed CTRCD was significantly higher in the Dox-ICI group than in the Dox group (38.1% vs. 17.4%, p = 0.042). Serum troponin-T level was significantly higher in the Dox-ICI group than in the Dox group (53.3 vs. 27.5 pg/mL, p = 0.023). Conclusions: ICIs may increase the risk of CTRCD when used with cardiotoxic agents. CTRCD should be monitored in patients treated with ICIs by cardiac biomarkers and echocardiography, including LV-GLS. Full article

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

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19 pages, 2264 KiB

Open AccessArticle

Prognostic Value of IGF2 mRNA-Binding Protein 3 (IGF2BP3) Intratumoral Expression in Melanoma Patients at the Time of Diagnosis: Comparative Analysis of RT-qPCR Versus Immunohistochemistry

by Beatriz Sánchez-Sendra, Silvia Pérez-Debén, José F. González-Muñoz, Amelia Murgui and Carlos Monteagudo

Cancers 2022, 14(9), 2319; https://doi.org/10.3390/cancers14092319 - 07 May 2022

Cited by 1 | Viewed by 1852

Abstract

Screening for prognostic biomarkers is crucial for clinical melanoma management. Insulin-like growth factor-II mRNA-binding protein 3 (IGF2BP3) has emerged as a potential melanoma diagnostic and prognostic biomarker. It is commonly tested by immunohistochemistry (IHC). Our study retrospectively examines IGF2BP3 mRNA and protein expression [...] Read more.

Screening for prognostic biomarkers is crucial for clinical melanoma management. Insulin-like growth factor-II mRNA-binding protein 3 (IGF2BP3) has emerged as a potential melanoma diagnostic and prognostic biomarker. It is commonly tested by immunohistochemistry (IHC). Our study retrospectively examines IGF2BP3 mRNA and protein expression in primary melanomas, their correlation with clinicopathologic factors, clinical outcome, and selected miRNAs expression, and their efficiency in predicting melanoma progression and survival. RT-qPCR and IHC on IGF2BP3 expression were performed in 61 cryopreserved and 63 formalin-fixed paraffin-embedded primary melanomas, respectively, and correlated to clinicopathologic factors, distant metastasis-free survival (DMFS), and melanoma -specific survival (MSS). The correlation between RT-qPCR and IHC was significant but moderate. IGF2BP3 mRNA showed a stronger association with clinicopathologic factors (Breslow thickness, ulceration, mitosis rate, growth phase, development of metastasis, and melanoma-specific survival) than its protein counterpart. Interestingly, higher IGF2BP3 mRNA expression was detected in primary melanomas that further metastasized to distant sites and was an independent prognostic factor for the risk of unfavorable DMFS and MSS. RT-qPCR outperformed IHC in sensitivity and in predicting worse clinical outcomes. Therefore, RT-qPCR may successfully be implemented for routine IGF2BP3 assessing for the selection of melanoma patients with a higher risk of developing distant metastasis and dying of melanoma. Full article

(This article belongs to the Special Issue Bio-Pathological Markers for the Diagnosis and Therapy of Cancers, Volume II)

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10 pages, 777 KiB

Open AccessSystematic Review

Optimal Clinical Target Volume of Radiotherapy Based on Microscopic Extension around the Primary Gross Tumor in Non-Small-Cell Lung Cancer: A Systematic Review

by Yukihisa Tamaki, Norihiro Aibe, Takafumi Komiyama, Satoshi Nagasaka, Toshiyuki Imagumbai, Tomoko Itazawa, Hiroshi Onishi, Tetsuo Akimoto, Yasushi Nagata and Yuko Nakayama

Cancers 2022, 14(9), 2318; https://doi.org/10.3390/cancers14092318 - 07 May 2022

Cited by 1 | Viewed by 2114

Abstract

A crucial issue in radical radiation therapy for non-small-cell lung cancer is how to define the clinical target volume (CTV). Although the scope of microscopic extension (ME) and microscopic proximal bronchial extension (PBE) from a primary tumor should be considered when defining the [...] Read more.

A crucial issue in radical radiation therapy for non-small-cell lung cancer is how to define the clinical target volume (CTV). Although the scope of microscopic extension (ME) and microscopic proximal bronchial extension (PBE) from a primary tumor should be considered when defining the CTV, there has been limited research on ME and PBE. Therefore, we conducted this systematic review. The PubMed, ICHUSHI (Japanese database), and Cochrane Library databases were searched, and 816 articles were initially retrieved. After primary and secondary screenings, eight articles were ultimately selected. The results of this systematic review suggest the importance of a 0 mm margin in stereotactic radiotherapy for early-stage cancer and a 5–8 mm margin in curative irradiation for locally advanced cancer. Regarding PBE, this review yielded the conclusion that it is appropriate to consider the addition of an approximately 15 mm margin from the bronchial vasculature. Although there were few articles with a high level of evidence, this systematic review enabled us to collate results from previous studies and to provide recommendations, to some extent, regarding the CTV margin in the current clinical environment, where high-precision radiation therapy, such as image-guided radiotherapy and intensity-modulated radiotherapy, is predominant. Full article

(This article belongs to the Topic Cancer Biology and Radiation Therapy)

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Open AccessReview

Circulating miRNAs in Breast Cancer Diagnosis and Prognosis

by Barbara Cardinali, Roberta Tasso, Patrizia Piccioli, Maria Chiara Ciferri, Rodolfo Quarto and Lucia Del Mastro

Cancers 2022, 14(9), 2317; https://doi.org/10.3390/cancers14092317 - 07 May 2022

Cited by 18 | Viewed by 3716

Abstract

Great improvement has been made in the diagnosis and therapy of breast cancer patients. However, the identification of biomarkers for early diagnosis, prognosis, therapy assessment and monitoring, including drug resistance and the early detection of micro-metastases, is still lacking. Recently, circulating microRNAs (miRNAs), [...] Read more.

Great improvement has been made in the diagnosis and therapy of breast cancer patients. However, the identification of biomarkers for early diagnosis, prognosis, therapy assessment and monitoring, including drug resistance and the early detection of micro-metastases, is still lacking. Recently, circulating microRNAs (miRNAs), circulating freely in the blood stream or entrapped in extracellular vesicles (EVs), have been shown to have a potential diagnostic, prognostic or predictive power. In this review, recent findings are summarized, both at a preclinical and clinical level, related to miRNA applicability in the context of breast cancer. Different aspects, including clinical and technical challenges, are discussed, describing the potentialities of miRNA use in breast cancer. Even though more methodological standardized studies conducted in larger and selected patient cohorts are needed to support the effective clinical utility of miRNA as biomarkers, they could represent novel and accessible tools to be transferred into clinical practice. Full article

(This article belongs to the Special Issue microRNA and Oxidative Drugs in Cancer Therapy and Prevention)

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Cancers, Volume 14, Issue 9 (May-1 2022) – 299 articles

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