Cancers

14 pages, 4378 KiB

Open AccessArticle

The Epidemiological Particularities of Malignant Hemopathies in French Guiana: 2005–2014

by Mathieu Nacher, Qiannan Wang, Beatrice Cenciu, Alolia Aboikoni, Florin Santa, Fabrice Quet, Fanja Vergeade, Antoine Adenis, Nathalie Deschamps and Kinan Drak Alsibai

Cancers 2024, 16(11), 2128; https://doi.org/10.3390/cancers16112128 (registering DOI) - 3 Jun 2024

Abstract

French Guiana is a French Overseas territory with singular features: it has a high prevalence of HIV and HTLV-1, its population is ethnically mixed, with widespread poverty, and up to 20% of the population lives in geographic isolation. In this context, we used [...] Read more.

French Guiana is a French Overseas territory with singular features: it has a high prevalence of HIV and HTLV-1, its population is ethnically mixed, with widespread poverty, and up to 20% of the population lives in geographic isolation. In this context, we used registry data to estimate incidence and mortality due to hematological malignancies and to compare them with France and tropical Latin America. ICD codes C90 and C88 were compiled between 2005 and 2014. The direct standardization of age structure was performed using the world population. Survival analysis was performed, and Kaplan–Meier curves were drawn. The overall standardized incidence rate was 32.9 per 100,000 male years and 24.5 per 100,000 female years. Between 2005 and 2009, the standardized incidence rate was 29.6 per 100,000 among men and 23.6 per 100,000 among women, and between 2010 and 2014, it was 35.6 per 100,000 among men and 25.2 per 100,000 among women. Multiple myeloma/plasmocytoma and mature t/NK cell lymphomas, notably adult t-cell lymphoma/leukemia due to HTLV-1 infection, were the two most common hematologic malignancies and causes of death. Non-Hodgkin’s lymphoma incidence estimates were greater than global estimates. After adjusting for age, sex, and type of malignancy, people born in a foreign country independently had a poorer case-fatality rate, presumably reflecting difficulties in accessing care. The epidemiology of hematological malignancies in French Guiana has features that distinguish it from mainland France or from Latin America. The incidence of multiple myeloma and adult t-cell lymphoma/leukemia was significantly greater in French Guiana than in France or other Latin American countries. Full article

(This article belongs to the Section Cancer Epidemiology and Prevention)

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11 pages, 640 KiB

Open AccessArticle

Dose-Escalated Radiotherapy for Primary Tracheobronchial Adenoid Cystic Carcinoma

by Jeong Ha Lee, Jeong Yun Jang, Jae Myoung Noh, Kyungmi Yang and Hongryull Pyo

Cancers 2024, 16(11), 2127; https://doi.org/10.3390/cancers16112127 (registering DOI) - 3 Jun 2024

Abstract

Primary tracheobronchial adenoid cystic carcinoma (ACC) is a rare malignancy, so the optimal radiotherapy (RT) dose remains unestablished. We aimed to evaluate the effectiveness of dose-escalated RT for primary tracheobronchial ACC. We retrospectively reviewed 48 patients who had undergone definitive or postoperative RT. [...] Read more.

Primary tracheobronchial adenoid cystic carcinoma (ACC) is a rare malignancy, so the optimal radiotherapy (RT) dose remains unestablished. We aimed to evaluate the effectiveness of dose-escalated RT for primary tracheobronchial ACC. We retrospectively reviewed 48 patients who had undergone definitive or postoperative RT. Patients classified into the low- and high-dose groups received RT doses <70.0 and ≥70.0 Gy in EQD2, respectively. The primary endpoint was freedom from local progression (FFLP) and overall survival (OS). Throughout the follow-up period, seven patients (14.6%) experienced local progression, while 31 (64.6%) exhibited distant metastasis, most commonly in the lungs. In total, the 5-year FFLP and OS rates were 85.7 and 84.7%, respectively. Multivariate analysis revealed that regional lymph node metastasis at diagnosis and receipt of definitive RT were associated with poorer OS. In the subgroup analysis, the definitive RT group had a 5-year FFLP rate of 33.3 and 78.2% in the low- and high-dose groups (p = 0.065), whereas 5-year OS rates were 66.7 and 79.0%, respectively (p = 0.022). Four patients (8.3%) experienced Grade 3 toxicity with tracheal or main bronchus stenosis. Dose-escalated RT with conventional fractionation may be effective in patients with tracheobronchial ACC, especially for a definitive aim. Full article

(This article belongs to the Section Cancer Therapy)

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20 pages, 1390 KiB

Open AccessReview

Spontaneous Tumor Regression and Reversion: Insights and Associations with Reduced Dietary Phosphate

by Ronald B. Brown

Cancers 2024, 16(11), 2126; https://doi.org/10.3390/cancers16112126 (registering DOI) - 3 Jun 2024

Abstract

Tumors that spontaneously shrink from unknown causes in tumor regression, and that return to normal cells in tumor reversion, are phenomena with the potential to contribute new knowledge and novel therapies for cancer patient survival. Tumorigenesis is associated with dysregulated phosphate metabolism and [...] Read more.

Tumors that spontaneously shrink from unknown causes in tumor regression, and that return to normal cells in tumor reversion, are phenomena with the potential to contribute new knowledge and novel therapies for cancer patient survival. Tumorigenesis is associated with dysregulated phosphate metabolism and an increased transport of phosphate into tumor cells, potentially mediated by phosphate overload from excessive dietary phosphate intake, a significant problem in Western societies. This paper proposes that reduced dietary phosphate overload and reregulated phosphate metabolism may reverse an imbalance of kinases and phosphatases in cell signaling and cellular proliferation, thereby activating autophagy in tumor regression and reversion. Dietary phosphate can also be reduced by sickness-associated anorexia, fasting-mimicking diets, and other diets low in phosphate, all of which have been associated with tumor regression. Tumor reversion has also been demonstrated by transplanting cancer cells into a healthy microenvironment, plausibly associated with normal cellular phosphate concentrations. Evidence also suggests that the sequestration and containment of excessive phosphate within encapsulated tumors is protective in cancer patients, preventing the release of potentially lethal amounts of phosphate into the general circulation. Reducing dietary phosphate overload has the potential to provide a novel, safe, and effective reversion therapy for cancer patients, and further research is warranted. Full article

(This article belongs to the Special Issue Clinical Research on the Relationship between Diet and Cancer Development)

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21 pages, 341 KiB

Open AccessReview

The Promotive and Inhibitory Role of Long Non-Coding RNAs in Endometrial Cancer Course—A Review

by Patryk Jasielski, Izabela Zawlik, Anna Bogaczyk, Natalia Potocka, Sylwia Paszek, Michał Maźniak, Aleksandra Witkoś, Adrianna Korzystka, Aleksandra Kmieć and Tomasz Kluz

Cancers 2024, 16(11), 2125; https://doi.org/10.3390/cancers16112125 (registering DOI) - 3 Jun 2024

Abstract

Endometrial cancer is one of the most common malignant tumours in women. The development of this tumour is associated with several genetic disorders, many of which are still unknown. One type of RNA molecules currently being intensively studied in many types of cancer [...] Read more.

Endometrial cancer is one of the most common malignant tumours in women. The development of this tumour is associated with several genetic disorders, many of which are still unknown. One type of RNA molecules currently being intensively studied in many types of cancer are long non-coding RNAs (lncRNAs). LncRNA-coding genes occupy a large fraction of the human genome. LncRNAs regulate many aspects of cell development, metabolism, and other physiological processes. Diverse types of lncRNA can function as a tumour suppressor or an oncogene that can alter migration, invasion, cell proliferation, apoptosis, and immune system response. Recent studies suggest that selected lncRNAs are important in an endometrial cancer course. Our article describes over 70 lncRNAs involved in the development of endometrial cancer, which were studied via in vivo and in vitro research. It was proved that lncRNAs could both promote and inhibit the development of endometrial cancer. In the future, lncRNAs may become an important therapeutic target. The aim of this study is to review the role of lncRNAs in the development of carcinoma of uterine body. Full article

(This article belongs to the Special Issue Endometrial Cancer: Old Questions and New Perspectives (Volume II))

11 pages, 236 KiB

Open AccessArticle

Past Happiness and Broken Future Horizon of Oncological Patients during Chemotherapy—A Quantitative Exploration of a Phenomenological Hypothesis

by Magdalena Fryze, Patrycja Wisniewska, Jadwiga Wiertlewska-Bielarz and Marcin Moskalewicz

Cancers 2024, 16(11), 2124; https://doi.org/10.3390/cancers16112124 (registering DOI) - 2 Jun 2024

Abstract

Understanding the impact of cancer on the experience of time is crucial in the context of hope and recovery. This study, a follow-up to a previous qualitative study of ovarian cancer patients – explored two types of such experiences—the memory of past happiness [...] Read more.

Understanding the impact of cancer on the experience of time is crucial in the context of hope and recovery. This study, a follow-up to a previous qualitative study of ovarian cancer patients – explored two types of such experiences—the memory of past happiness and the limited future planning. A sociodemographic questionnaire with nine questions about the experience of time was used on a convenience sample of 202 patients with various cancers, predominantly women with breast, ovarian, and cervical cancer. It was found that the respondents experienced increased focus on the present, decreased focus on the future, and a sense of unpredictability, with a relatively short temporal horizon measured in weeks and months, not years. Almost half of the respondents (46%) measured time during treatment by the rhythm of chemotherapy and check-ups, which thus appeared as the most meaningful events. The increase in the frequency with which patients underwent chemotherapy mildly affected their focus on the present (R = 0.25, p < 0.05), likely because of the discomfort of the side effects. The correlations between age and time in treatment, on the one hand, and the experience of time, on the other, were negligible. Changed temporal experience during chemotherapy is a factor that can have an impact on patients’ well-being and ability to cope with the disease. It thus should be taken into account when planning oncology care. Full article

(This article belongs to the Special Issue Quality of Life and Side Effects Management in Cancer Treatment (Volume II))

30 pages, 2185 KiB

Open AccessReview

The Many Roads from Alternative Splicing to Cancer: Molecular Mechanisms Involving Driver Genes

by Francisco Gimeno-Valiente, Gerardo López-Rodas, Josefa Castillo and Luis Franco

Cancers 2024, 16(11), 2123; https://doi.org/10.3390/cancers16112123 (registering DOI) - 1 Jun 2024

Abstract

Cancer driver genes are either oncogenes or tumour suppressor genes that are classically activated or inactivated, respectively, by driver mutations. Alternative splicing—which produces various mature mRNAs and, eventually, protein variants from a single gene—may also result in driving neoplastic transformation because of the [...] Read more.

Cancer driver genes are either oncogenes or tumour suppressor genes that are classically activated or inactivated, respectively, by driver mutations. Alternative splicing—which produces various mature mRNAs and, eventually, protein variants from a single gene—may also result in driving neoplastic transformation because of the different and often opposed functions of the variants of driver genes. The present review analyses the different alternative splicing events that result in driving neoplastic transformation, with an emphasis on their molecular mechanisms. To do this, we collected a list of 568 gene drivers of cancer and revised the literature to select those involved in the alternative splicing of other genes as well as those in which its pre-mRNA is subject to alternative splicing, with the result, in both cases, of producing an oncogenic isoform. Thirty-one genes fall into the first category, which includes splicing factors and components of the spliceosome and splicing regulators. In the second category, namely that comprising driver genes in which alternative splicing produces the oncogenic isoform, 168 genes were found. Then, we grouped them according to the molecular mechanisms responsible for alternative splicing yielding oncogenic isoforms, namely, mutations in cis splicing-determining elements, other causes involving non-mutated cis elements, changes in splicing factors, and epigenetic and chromatin-related changes. The data given in the present review substantiate the idea that aberrant splicing may regulate the activation of proto-oncogenes or inactivation of tumour suppressor genes and details on the mechanisms involved are given for more than 40 driver genes. Full article

(This article belongs to the Special Issue The Role of Alternative Splicing in Cancer)

33 pages, 6422 KiB

Open AccessReview

The Role of MRI in Breast Cancer and Breast Conservation Therapy

by Iman Washington, Russell F. Palm, Julia White, Stephen A. Rosenberg and Dana Ataya

Cancers 2024, 16(11), 2122; https://doi.org/10.3390/cancers16112122 (registering DOI) - 1 Jun 2024

Abstract

Contrast-enhanced breast MRI has an established role in aiding in the detection, evaluation, and management of breast cancer. This article discusses MRI sequences, the clinical utility of MRI, and how MRI has been evaluated for use in breast radiotherapy treatment planning. We highlight [...] Read more.

Contrast-enhanced breast MRI has an established role in aiding in the detection, evaluation, and management of breast cancer. This article discusses MRI sequences, the clinical utility of MRI, and how MRI has been evaluated for use in breast radiotherapy treatment planning. We highlight the contribution of MRI in the decision-making regarding selecting appropriate candidates for breast conservation therapy and review the emerging role of MRI-guided breast radiotherapy. Full article

(This article belongs to the Special Issue New Approaches in Radiotherapy for Cancer)

21 pages, 2116 KiB

Open AccessArticle

Genetic Prognostic Factors in Adult Diffuse Gliomas: A 10-Year Experience at a Single Institution

by Amir Barzegar Behrooz, Hadi Darzi Ramandi, Hamid Latifi-Navid, Payam Peymani, Rahil Tarharoudi, Nasrin Momeni, Mohammad Mehdi Sabaghpour Azarian, Sherif Eltonsy, Ahmad Pour-Rashidi and Saeid Ghavami

Cancers 2024, 16(11), 2121; https://doi.org/10.3390/cancers16112121 (registering DOI) - 1 Jun 2024

Abstract

Gliomas are primary brain lesions involving cerebral structures without well-defined boundaries and constitute the most prevalent central nervous system (CNS) neoplasms. Among gliomas, glioblastoma (GB) is a glioma of the highest grade and is associated with a grim prognosis. We examined how clinical [...] Read more.

Gliomas are primary brain lesions involving cerebral structures without well-defined boundaries and constitute the most prevalent central nervous system (CNS) neoplasms. Among gliomas, glioblastoma (GB) is a glioma of the highest grade and is associated with a grim prognosis. We examined how clinical variables and molecular profiles may have affected overall survival (OS) over the past ten years. A retrospective study was conducted at Sina Hospital in Tehran, Iran and examined patients with confirmed glioma diagnoses between 2012 and 2020. We evaluated the correlation between OS in GB patients and sociodemographic as well as clinical factors and molecular profiling based on IDH1, O-6-Methylguanine-DNA Methyltransferase (MGMT), TERTp, and epidermal growth factor receptor (EGFR) amplification (EGFR-amp) status. Kaplan–Meier and multivariate Cox regression models were used to assess patient survival. A total of 178 patients were enrolled in the study. The median OS was 20 months, with a 2-year survival rate of 61.0%. Among the 127 patients with available IDH measurements, 100 (78.7%) exhibited mutated IDH1 (IDH1-mut) tumors. Of the 127 patients with assessed MGMT promoter methylation (MGMTp-met), 89 (70.1%) had MGMT methylated tumors. Mutant TERTp (TERTp-mut) was detected in 20 out of 127 cases (15.7%), while wildtype TERTp (wildtype TERTp-wt) was observed in 107 cases (84.3%). Analyses using multivariable models revealed that age at histological grade (p < 0.0001), adjuvant radiotherapy (p < 0.018), IDH1 status (p < 0.043), and TERT-p status (p < 0.014) were independently associated with OS. Our study demonstrates that patients with higher tumor histological grades who had received adjuvant radiotherapy exhibited IDH1-mut or presented with TERTp-wt experienced improved OS. Besides, an interesting finding showed an association between methylation of MGMTp and TERTp status with tumor location. Full article

(This article belongs to the Topic Findings, Insights and Perspectives on Central Nervous System Tumors)

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9 pages, 2583 KiB

Open AccessArticle

Prognostic Impact of Mucin Expression in Curatively Resected Ampulla of Vater Cancer

by Byeong Gwan Noh, Hyung Il Seo, Young Mok Park, Su-Bin Song, Suk Kim, Seung Baek Hong, Nam Kyung Lee, Jonghyun Lee, Tae In Kim, Chae Hwa Kwon and Ji Hyun Ahn

Cancers 2024, 16(11), 2120; https://doi.org/10.3390/cancers16112120 (registering DOI) - 1 Jun 2024

Abstract

Introduction: Mucins play a pivotal role in epithelial carcinogenesis; however, their role remains elusive in ampulla of Vater (AoV) cancer, regardless of histological subtype. Therefore, we investigated the clinical significance of MUC1, MUC2, MUC5AC, and MUC6 expression in AoV cancer. Methods: Using [...] Read more.

Introduction: Mucins play a pivotal role in epithelial carcinogenesis; however, their role remains elusive in ampulla of Vater (AoV) cancer, regardless of histological subtype. Therefore, we investigated the clinical significance of MUC1, MUC2, MUC5AC, and MUC6 expression in AoV cancer. Methods: Using samples from 68 patients with AoV cancer, we performed immunohistochemical staining for MUC1, MUC2, MUC5AC, and MUC6 using a tissue microarray. Subsequently, we analyzed their expression patterns in relation to clinicopathological parameters and patient outcomes. Results: Of the patients, 98.5% exhibited positive expression for MUC1, while MUC2, MUC5AC, and MUC6 were expressed in 44.1%, 47.1%, and 41.2% of the patients, respectively. Correlation analyses between mucin expression and clinicopathological factors revealed no significant associations, except between MUC5AC expression and N stage. Univariate analysis demonstrated significant associations between MUC5AC expression and overall survival (OS). Multivariate analysis further confirmed that MUC5AC expression was a significant predictor of OS, along with the N stage. However, MUC5AC expression was not meaningfully associated with recurrence-free survival (RFS). The patients positive for MUC5AC expression had a considerably shorter OS than those with negative expression. Conclusions: Our study provides insights into the clinical impact of mucins on AoV cancer, regardless of the histological subtype. Although MUC1 expression is universal, MUC5AC expression is a significant prognostic indicator that correlates with lymph node metastasis and poor OS. These results emphasize the possible utility of MUC5AC as a biomarker for extensive lymph node dissection and the prognostic evaluation of patients with AoV cancer. Full article

(This article belongs to the Special Issue Current Clinical Studies of Pancreatic Ductal Adenocarcinoma)

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16 pages, 3279 KiB

Open AccessArticle

Insights into MLH1 Methylation in Endometrial Adenocarcinoma through Pyrosequencing Analysis: A Retrospective Observational Study

by Fábio França Vieira e Silva, Andrea Ballini, Vito Carlo Alberto Caponio, Mario Pérez-Sayáns, Marina Gándara Cortés, Laura Isabel Rojo-Álvarez, Abel García-García, José Manuel Suaréz-Peñaranda, Marina Di Domenico and María Elena Padín-Iruegas

Cancers 2024, 16(11), 2119; https://doi.org/10.3390/cancers16112119 (registering DOI) - 1 Jun 2024

Abstract

Background: In cancer care, the MLH1 gene is crucial for DNA mismatch repair (MMR), serving as a vital tumor suppressor. Evaluating MLH1 protein expression status, followed by analysis of MLH1 promoter methylation, has become a key diagnostic and prognostic approach. Our study [...] Read more.

Background: In cancer care, the MLH1 gene is crucial for DNA mismatch repair (MMR), serving as a vital tumor suppressor. Evaluating MLH1 protein expression status, followed by analysis of MLH1 promoter methylation, has become a key diagnostic and prognostic approach. Our study investigates the complex link between MLH1 methylation and prognosis in endometrial adenocarcinoma (EA) patients. Methodology: MLH1 methylation status was accessed by a Pyrosequencing (PSQ) assay. Qualitative positivity for methylation was established if it exceeded the 11% cut-off; as well, a quantitative methylation analysis was conducted to establish correlations with clinicopathological data, relapse-free survival, and disease-free survival. Results: Our study revealed that 33.3% of patients without MLH1 methylation experienced relapses, surpassing the 23.3% in patients with methylation. Furthermore, 16.7% of patients without methylation succumbed to death, with a slightly higher rate of 17.6% in methylated patients. Qualitative comparisons highlighted that the mean methylation rate in patients experiencing relapse was 35.8%, whereas in those without relapse, it was 42.2%. This pattern persisted in disease-specific survival (DSS), where deceased patients exhibited a higher mean methylation level of 49.1% compared to living patients with 38.8%. Conclusions: Our findings emphasize the efficacy of PSQ for evaluating MLH1 methylation. While unmethylation appears to be associated with a higher relapse rate, the survival rate does not seem to be influenced by methylation. Quantitative percentages suggest that elevated MLH1 methylation is linked to relapse and mortality, though a study with a larger sample size would be essential for statistically significant results. Full article

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

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11 pages, 4061 KiB

Open AccessReview

Flow Cytometry Profiling of Plasmacytoid Dendritic Cell Neoplasms

by Siba El Hussein and Wei Wang

Cancers 2024, 16(11), 2118; https://doi.org/10.3390/cancers16112118 (registering DOI) - 1 Jun 2024

Abstract

In this review, we aim to provide a summary of the diverse immunophenotypic presentations of distinct entities associated with plasmacytoid dendritic cell (pDC) proliferation. These entities include the following: (1) blastic plasmacytoid dendritic cell neoplasm (BPDCN); (2) mature pDC proliferation (MPDCP), most commonly [...] Read more.

In this review, we aim to provide a summary of the diverse immunophenotypic presentations of distinct entities associated with plasmacytoid dendritic cell (pDC) proliferation. These entities include the following: (1) blastic plasmacytoid dendritic cell neoplasm (BPDCN); (2) mature pDC proliferation (MPDCP), most commonly seen in chronic myelomonocytic leukemia (CMML); and (3) myeloid neoplasms with pDC differentiation, in which pDCs show a spectrum of maturation from early immature pDCs to mature forms, most commonly seen in acute myeloid leukemia (pDC-AML). Our aim is to provide a flow cytometry diagnostic approach to these distinct and sometimes challenging entities and to clarify the immunophenotypic spectrum of neoplastic pDCs in different disease presentations. In this review, we also cover the strategies in the evaluation of residual disease, as well as the challenges and pitfalls we face in the setting of immune and targeted therapy when evaluating residual disease by flow cytometry. The differential diagnosis will also be discussed, as blasts in some AML cases can have a pDC-like immunophenotype, mimicking pDCs. Full article

(This article belongs to the Special Issue Flow Cytometry of Hematological Malignancies)

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13 pages, 1068 KiB

Open AccessArticle

The Association of Ethnicity and Oncologic Outcomes for Oral Cavity Squamous Cell Carcinoma (OSCC)

by Kiana Mahboubi, Steven C. Nakoneshny, Khara Sauro, Samuel Roberts, Rob Hart, T. Wayne Matthews, Joseph Dort and Shamir P. Chandarana

Cancers 2024, 16(11), 2117; https://doi.org/10.3390/cancers16112117 (registering DOI) - 31 May 2024

Abstract

(1) Background: To compare oncologic outcomes of South Asian (SA) patients treated for oral squamous cell carcinoma (OSCC) to the general population. (2) Methods: Adult patients who underwent surgical resection of OSCC +/− adjuvant treatment between 2009 and 2022 (N = 697) at [...] Read more.

(1) Background: To compare oncologic outcomes of South Asian (SA) patients treated for oral squamous cell carcinoma (OSCC) to the general population. (2) Methods: Adult patients who underwent surgical resection of OSCC +/− adjuvant treatment between 2009 and 2022 (N = 697) at a regional cancer centre in Canada were included. SA patients, identified using a validated method, were compared to non-SA patients. Kaplan–Meier methods were used to compare the primary outcomes, disease-specific survival (DSS) and recurrence-free survival (RFS) across baseline univariate characteristics, including betel nut consumption. Median follow-up time was 36.4 months. Cox proportional hazard models were used to identify independent predictors of survival with significance set at p < 0.05. (3) Results: SA patients (9% of cohort, N = 64) were significantly younger and had lower rates of smoking and alcohol consumption compared to non-SA patients (p < 0.05). SA patients had a two-fold higher risk of recurrence and significantly worse disease-specific survival, even after adjusting for stage and high-risk features [RFS: HR 2.01 (1.28–3.14), DSS: HR 1.79 (1.12–2.88)]. The consumption of betel nut was not associated with outcomes. (4) Conclusion: SA patients had significantly worse oncologic outcomes, even after controlling for known predictors of poor prognosis. These findings are novel and can inform personalized treatment decisions and influence public health policies when managing patients with different ethnic backgrounds. Full article

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

22 pages, 633 KiB

Open AccessArticle

Implementing Multifactorial Risk Assessment with Polygenic Risk Scores for Personalized Breast Cancer Screening in the Population Setting: Challenges and Opportunities

by Meghan J. Walker, Kristina M. Blackmore, Amy Chang, Laurence Lambert-Côté, Annie Turgeon, Antonis C. Antoniou, Kathleen A. Bell, Mireille J. M. Broeders, Jennifer D. Brooks, Tim Carver, Jocelyne Chiquette, Philippe Després, Douglas F. Easton, Andrea Eisen, Laurence Eloy, D. Gareth Evans, Samantha Fienberg, Yann Joly, Raymond H. Kim, Shana J. Kim, Bartha M. Knoppers, Aisha K. Lofters, Hermann Nabi, Jean-Sébastien Paquette, Nora Pashayan, Amanda J. Sheppard, Tracy L. Stockley, Michel Dorval, Jacques Simard and Anna M. Chiarelli Show full author list Hide full author list

Cancers 2024, 16(11), 2116; https://doi.org/10.3390/cancers16112116 (registering DOI) - 31 May 2024

Abstract

Risk-stratified breast screening has been proposed as a strategy to overcome the limitations of age-based screening. A prospective cohort study was undertaken within the PERSPECTIVE I&I project, which will generate the first Canadian evidence on multifactorial breast cancer risk assessment in the population [...] Read more.

Risk-stratified breast screening has been proposed as a strategy to overcome the limitations of age-based screening. A prospective cohort study was undertaken within the PERSPECTIVE I&I project, which will generate the first Canadian evidence on multifactorial breast cancer risk assessment in the population setting to inform the implementation of risk-stratified screening. Recruited females aged 40–69 unaffected by breast cancer, with a previous mammogram, underwent multifactorial breast cancer risk assessment. The adoption of multifactorial risk assessment, the effectiveness of methods for collecting risk factor information and the costs of risk assessment were examined. Associations between participant characteristics and study sites, as well as data collection methods, were assessed using logistic regression; all p-values are two-sided. Of the 4246 participants recruited, 88.4% completed a risk assessment, with 79.8%, 15.7% and 4.4% estimated at average, higher than average and high risk, respectively. The total per-participant cost for risk assessment was CAD 315. Participants who chose to provide risk factor information on paper/telephone (27.2%) vs. online were more likely to be older (p = 0.021), not born in Canada (p = 0.043), visible minorities (p = 0.01) and have a lower attained education (p < 0.0001) and perceived fair/poor health (p < 0.001). The 34.4% of participants requiring risk factor verification for missing/unusual values were more likely to be visible minorities (p = 0.009) and have a lower attained education (p ≤ 0.006). This study demonstrates the feasibility of risk assessment for risk-stratified screening at the population level. Implementation should incorporate an equity lens to ensure cancer-screening disparities are not widened. Full article

(This article belongs to the Special Issue New Era of Cancer Research: From Large-Scale Cohorts to Big-Data)

28 pages, 1007 KiB

Open AccessReview

Phospholipid Acyltransferases: Characterization and Involvement of the Enzymes in Metabolic and Cancer Diseases

by Jan Korbecki, Mateusz Bosiacki, Maciej Pilarczyk, Magdalena Gąssowska-Dobrowolska, Paweł Jarmużek, Izabela Szućko-Kociuba, Justyna Kulik-Sajewicz, Dariusz Chlubek and Irena Baranowska-Bosiacka

Cancers 2024, 16(11), 2115; https://doi.org/10.3390/cancers16112115 (registering DOI) - 31 May 2024

Abstract

This review delves into the enzymatic processes governing the initial stages of glycerophospholipid (phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine) and triacylglycerol synthesis. The key enzymes under scrutiny include GPAT and AGPAT. Additionally, as most AGPATs exhibit LPLAT activity, enzymes participating in the Lands cycle with [...] Read more.

This review delves into the enzymatic processes governing the initial stages of glycerophospholipid (phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine) and triacylglycerol synthesis. The key enzymes under scrutiny include GPAT and AGPAT. Additionally, as most AGPATs exhibit LPLAT activity, enzymes participating in the Lands cycle with similar functions are also covered. The review begins by discussing the properties of these enzymes, emphasizing their specificity in enzymatic reactions, notably the incorporation of polyunsaturated fatty acids (PUFAs) such as arachidonic acid and docosahexaenoic acid (DHA) into phospholipids. The paper sheds light on the intricate involvement of these enzymes in various diseases, including obesity, insulin resistance, and cancer. To underscore the relevance of these enzymes in cancer processes, a bioinformatics analysis was conducted. The expression levels of the described enzymes were correlated with the overall survival of patients across 33 different types of cancer using the GEPIA portal. This review further explores the potential therapeutic implications of inhibiting these enzymes in the treatment of metabolic diseases and cancer. By elucidating the intricate enzymatic pathways involved in lipid synthesis and their impact on various pathological conditions, this paper contributes to a comprehensive understanding of these processes and their potential as therapeutic targets. Full article

(This article belongs to the Section Tumor Microenvironment)

11 pages, 369 KiB

Open AccessArticle

Current Status and Management of Chronic Myeloid Leukemia in the Gulf Region: Survey Results and Expert Opinion

by Giuseppe Saglio, Mohamed Yassin, Ahmad Alhuraiji, Amar Lal, Arif Alam, Faraz Khan, Fatima Khadada, Hani Osman, Islam Elkonaissi, Mahmoud Marashi, Mohamed Abuhaleeqa, Murtadha Al-Khabori, Ramesh Pandita, Salam Al-Kindi, Shakir Bahzad, Dayane Daou and Yasmin Al Qudah

Cancers 2024, 16(11), 2114; https://doi.org/10.3390/cancers16112114 - 31 May 2024

Abstract

Studies on chronic myeloid leukemia (CML) in the Gulf region are scarce, consisting of a survey and expert meeting that included 15 experts in 2023 which discussed CML diagnosis, testing, treatment objectives, toxicities, and discontinuation in the Gulf region. Most patients were reported [...] Read more.

Studies on chronic myeloid leukemia (CML) in the Gulf region are scarce, consisting of a survey and expert meeting that included 15 experts in 2023 which discussed CML diagnosis, testing, treatment objectives, toxicities, and discontinuation in the Gulf region. Most patients were reported to be in first-line therapy, and the most common treatments were imatinib/imatinib generic in first-line and dasatinib in second- and third-lines. Mutation analysis was not reported to be routinely performed at the time of diagnosis but rather in case of progression to accelerated/blast phase or any sign of loss of response. While all participants were aware that BCR-ABL should be monitored every three months during the first year of treatment, 10% reported monitoring BCR-ABL every six months in practice due to test cost and lab capability. The most important first-line therapy objective was “achievement of major molecular response” (MMR) in younger patients and “overall survival” in older ones. The most important treatment objectives were “MMR” and “early molecular response followed by prolongation of overall survival” in the short term and “treatment-free remission” in the long term. The current practices in CML in the Gulf region appear to be similar to global figures. Full article

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

19 pages, 3579 KiB

Open AccessArticle

The Role of Insulin-like Growth Factor Binding Protein (IGFBP)-2 in DNA Repair and Chemoresistance in Breast Cancer Cells

by Alaa Mohammedali, Kalina Biernacka, Rachel M. Barker, Jeff M. P. Holly and Claire M. Perks

Cancers 2024, 16(11), 2113; https://doi.org/10.3390/cancers16112113 - 31 May 2024

Abstract

The role if insulin-like growth factor binding protein-2 (IGFBP-2) in mediating chemoresistance in breast cancer cells has been demonstrated, but the mechanism of action is unclear. This study aimed to further investigate the role of IGFBP-2 in the DNA damage response induced by [...] Read more.

The role if insulin-like growth factor binding protein-2 (IGFBP-2) in mediating chemoresistance in breast cancer cells has been demonstrated, but the mechanism of action is unclear. This study aimed to further investigate the role of IGFBP-2 in the DNA damage response induced by etoposide in MCF-7, T47D (ER+ve), and MDA-MB-231 (ER-ve) breast cancer cell lines. In the presence or absence of etoposide, IGFBP-2 was silenced using siRNA in the ER-positive cell lines, or exogenous IGFBP-2 was added to the ER-negative MDA-MB-231 cells. Cell number and death were assessed using trypan blue dye exclusion assay, changes in abundance of proteins were monitored using Western blotting of whole cell lysates, and localization and abundance were determined using immunofluorescence and cell fractionation. Results from ER-positive cell lines demonstrated that upon exposure to etoposide, loss of IGFBP-2 enhanced cell death, and this was associated with a reduction in P-DNA-PKcs and an increase in γH2AX. Conversely, with ER-negative cells, the addition of IGFBP-2 in the presence of etoposide resulted in cell survival, an increase in P-DNA-PKcs, and a reduction in γH2AX. In summary, IGFBP-2 is a survival factor for breast cancer cells that is associated with enhancement of the DNA repair mechanism. Full article

(This article belongs to the Section Cancer Pathophysiology)

20 pages, 6308 KiB

Open AccessArticle

Cryopreserved Thyroid Tissue Autotransplant in Pediatric Age Patients: A Feasibility Study and Literature Review

by Claudio Spinelli, Marco Ghionzoli, Linda Idrissi Sahli, Silvia Visintainer, Carla Guglielmo, Chiara Cordola, Simone Lapi, Elisa Biagi, Angela Pucci, Riccardo Morganti, Silvia Martina Ferrari and Alessandro Antonelli

Cancers 2024, 16(11), 2112; https://doi.org/10.3390/cancers16112112 - 31 May 2024

Abstract

Background and aims: This paper aims to study an alternative solution to hormonal replacement therapy in specific groups of patients who underwent thyroidectomy during childhood or adulthood. After cryopreservation, thyroid autotransplantation could be an alternative solution which would allow us to use the [...] Read more.

Background and aims: This paper aims to study an alternative solution to hormonal replacement therapy in specific groups of patients who underwent thyroidectomy during childhood or adulthood. After cryopreservation, thyroid autotransplantation could be an alternative solution which would allow us to use the ability of the thyroid tissue of producing hormones according to the physiological needs of the body. Materials and methods: A feasibility study about the effects of the most modern cryopreservation techniques on the structural and functional integrity of the follicular cells of the thyroid tissue has been carried out. Patients who could benefit from the treatment have been found for both autotransplant techniques. Additionally, a literature review has been conducted. Results: The histological analysis has shown that cryopreservation does not alter the original architecture, and the culture examination that cell viability is successfully preserved. Moreover, both thyroid autotransplantation studies on animals and those on humans that were found in the literature have shown good results regarding the viability and functionality of the transplant. Conclusions: The viability of cryopreserved thyroid tissue found in this study is encouraging. Further studies to evaluate the levels of FT3, FT4 and thyroglobulin in thyroid tissue after cryopreservation are needed to verify that the secretory properties of the thyrocytes have been maintained intact. Furthermore, autotransplanted cases found in the literature do not have a long-term follow-up. Full article

(This article belongs to the Special Issue Classification, Risk Assessment and Clinical Management of Malignant Thyroid Nodules)

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13 pages, 425 KiB

Open AccessArticle

Mutations in Mismatch Repair Genes and Microsatellite Instability Status in Pancreatic Cancer

by Marina Emelyanova, Anna Ikonnikova, Alexander Pushkov, Elena Pudova, George Krasnov, Anna Popova, Ilya Zhanin, Darya Khomich, Ivan Abramov, Sergei Tjulandin, Dmitry Gryadunov and Ilya Pokataev

Cancers 2024, 16(11), 2111; https://doi.org/10.3390/cancers16112111 - 31 May 2024

Abstract

Patients with pancreatic cancer (PC) showing mismatch repair (MMR) deficiency may benefit from immunotherapy. Microsatellite instability (MSI) is a hallmark of MMR deficiency (MMR-D). Here, we estimated the prevalence of MSI in PC, investigated germline and somatic mutations in the three MMR genes [...] Read more.

Patients with pancreatic cancer (PC) showing mismatch repair (MMR) deficiency may benefit from immunotherapy. Microsatellite instability (MSI) is a hallmark of MMR deficiency (MMR-D). Here, we estimated the prevalence of MSI in PC, investigated germline and somatic mutations in the three MMR genes (MLH1, MSH2, and MSH6), and assessed the relationship between MMR genes mutations and MSI status in PC. Clinical specimens from PC patients were analyzed using targeted next-generation sequencing, including paired normal and tumor specimens from 155 patients, tumor-only specimens from 86 patients, and normal-only specimens from 379 patients. The MSI status of 235 PCs was assessed via PCR. Pathogenic/likely pathogenic (P/LP) germline variants in the MMR genes were identified in 1.1% of patients, while somatic variants were found in 2.6% of patients. No MSI-H tumors were detected. One patient carried two variants (P (VAF = 0.57) and LP (VAF = 0.25)) simultaneously; however, their germline/somatic status remains unknown due to the investigation focusing solely on the tumor and MSI analysis was not performed for this patient. MSI is rare in PC, even in tumors with MMR genes mutations. Our findings underscore the importance of assessing tumor MMR-D status in PC patients with confirmed Lynch syndrome when deciding whether to prescribe immunotherapy. Full article

(This article belongs to the Special Issue Advanced Research in Pancreatic Ductal Adenocarcinoma)

16 pages, 673 KiB

Open AccessArticle

Medication Risks and Their Association with Patient-Reported Outcomes in Inpatients with Cancer

by Maximilian Günther, Markus Schuler, Leopold Hentschel, Hanna Salm, Marie-Therese Schmitz and Ulrich Jaehde

Cancers 2024, 16(11), 2110; https://doi.org/10.3390/cancers16112110 (registering DOI) - 31 May 2024

Abstract

Background: We aimed to assess medication risks and determine factors influencing the health-related quality of life (HRQOL) in cancer inpatients. Methods: A retrospective analysis was conducted to identify drug-related problems (DRPs) based on medication reviews, including patient-reported outcomes (PROs). Multiple linear regression analyses [...] Read more.

Background: We aimed to assess medication risks and determine factors influencing the health-related quality of life (HRQOL) in cancer inpatients. Methods: A retrospective analysis was conducted to identify drug-related problems (DRPs) based on medication reviews, including patient-reported outcomes (PROs). Multiple linear regression analyses were performed to identify sociodemographic, disease-related, and drug therapy-related factors influencing changes from hospital admission to discharge in the scales of the EORTC QLQ-C30 questionnaire. Results: A total of 162 inpatients with various hematological and solid cancer diseases was analyzed. Patients received a mean of 11.6 drugs and 92.6% of patients exhibited polymedication resulting in a mean of 4.0 DRPs per patient. Based on PRO data, 21.5% of DRPs were identified. Multiple linear regression models described the variance of the changes in global HRQOL and physical function in a weak-to-moderate way. While drug therapy-related factors had no influence, relapse status and duration of hospital stay were identified as significant covariates for global HRQOL and physical function, respectively. Conclusion: This analysis describes underlying DRPs in a German cancer inpatient population. PROs provided valuable information for performing medication reviews. The multiple linear regression models for global HRQOL and physical function provided explanations for changes during hospital stay. Full article

(This article belongs to the Special Issue Correlating Patient-Reported Quality of Life before, during, and after Therapy with Objective Measures and Outcomes)

17 pages, 876 KiB

Open AccessArticle

Fertility-Preserving Treatments and Patient- and Parental Satisfaction on Fertility Counseling in a Cohort of Newly Diagnosed Boys and Girls with Childhood Hodgkin Lymphoma

by Katja C. E. Drechsel, Irene M. IJgosse, Sofie Slaats, Lisanne Raasen, Francis S. Stoutjesdijk, Eline van Dulmen-den Broeder, W. Hamish Wallace, Auke Beishuizen, Dieter Körholz, Christine Mauz-Körholz, Michaela Cepelova, Anne Uyttebroeck, Leila Ronceray, Gertjan J. L. Kaspers, Simone L. Broer and Margreet A. Veening

Cancers 2024, 16(11), 2109; https://doi.org/10.3390/cancers16112109 - 31 May 2024

Abstract

Abstract: Purpose: The purpose of this study is to evaluate the use of fertility-preserving (FP) treatments and fertility counseling that was offered in a cohort of newly diagnosed children with classical Hodgkin lymphoma (cHL). Methods: In this observational study, boys and girls [...] Read more.

Abstract: Purpose: The purpose of this study is to evaluate the use of fertility-preserving (FP) treatments and fertility counseling that was offered in a cohort of newly diagnosed children with classical Hodgkin lymphoma (cHL). Methods: In this observational study, boys and girls with cHL aged ≤ 18 years with scheduled treatment according to the EuroNet-PHL-C2 protocol were recruited from 18 sites (5 countries), between January 2017 and September 2021. In 2023, a subset of Dutch participants (aged ≥ 12 years at time of diagnosis) and parents/guardians were surveyed regarding fertility counseling. Results: A total of 101 boys and 104 girls were included. Most post-pubertal boys opted for semen cryopreservation pre-treatment (85% of expected). Invasive FP treatments were occasionally chosen for patients at a relatively low risk of fertility based on scheduled alkylating agent exposure (4/5 testicular biopsy, 4/4 oocyte, and 11/11 ovarian tissue cryopreservation). A total of 17 post-menarchal girls (20%) received GnRH-analogue co-treatment. Furthermore, 33/84 parents and 26/63 patients responded to the questionnaire. Most reported receiving fertility counseling (97%/89%). Statements regarding the timing and content of counseling were generally positive. Parents and patients considered fertility counseling important (94%/87% (strongly agreed) and most expressed concerns about (their child’s) fertility (at diagnosis 69%/46%, at present: 59%/42%). Conclusion: Systematic fertility counseling is crucial for all pediatric cHL patients and their families. FP treatment should be considered depending on the anticipated risk and patient factors. We encourage the development of a decision aid for FP in pediatric oncology. Full article

(This article belongs to the Topic Children’s Diseases, Family Management, and Quality of Life)

10 pages, 815 KiB

Open AccessArticle

Ponatinib as a Prophylactic or Pre-Emptive Strategy to Prevent Cytological Relapse after Allogeneic Stem Cell Transplantation in Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Transplanted in Complete Cytological Remission

by Anna Candoni, Patrizia Chiusolo, Davide Lazzarotto, Chiara Sartor, Michelina Dargenio, Sabina Chiaretti, Cristina Skert, Fabio Giglio, Silvia Trappolini, Nicola Stefano Fracchiolla, Sara Medici, Paola Bresciani, Angela Cuoghi and Cristina Papayannidis

Cancers 2024, 16(11), 2108; https://doi.org/10.3390/cancers16112108 - 31 May 2024

Abstract

The administration of TKIs after Allo-SCT in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) remains controversial, and the TKI approach (prophylactic, pre-emptive or salvage) is still heterogeneous in transplant centers. In this context, very little is known about the feasibility and safety [...] Read more.

The administration of TKIs after Allo-SCT in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) remains controversial, and the TKI approach (prophylactic, pre-emptive or salvage) is still heterogeneous in transplant centers. In this context, very little is known about the feasibility and safety of third-generation TKIs. In this paper, we analyze the efficacy and safety of ponatinib (PONA) administered after Allo-SCT to prevent cytologic relapse of Ph + ALL. This is a multicenter observational study including 48 patients (pts) with Ph + ALL (median age 49 years) who received PONA after Allo-SCT while in complete cytological remission (cCR); 26 (54%) had positive minimal residual disease (MRD pos) before Allo-SCT. PONA was administered after Allo-SCT prophylactically (starting with MRD neg) in 26 pts or pre-emptively (starting with MRD pos post-SCT and without hematological relapse) in 22 pts. Patients treated prophylactically with PONA started treatment earlier, at a median of 4.3 months (range 1.5–6) after Allo-SCT, than those treated pre-emptively, who started PONA at a median of 7.4 months (range 2–63) after Allo-SCT (p = 0.01). The median starting dose of PONA was 30 mg/day (range 15–45). A dose reduction was required in 10/48 (21%) of cases, but a permanent discontinuation of PONA, due to toxicity, was required in only 5/48 pts (10.5%). No deaths due to PONA-related adverse events (AEs) were reported. The median follow-up time after Allo-SCT was 34 months (range 7.7–118). At the last follow-up, the median duration of PONA therapy was 22 months (range 2–100). The 5-year OS and RFS after Allo-SCT were 92% and 71%, respectively. The 5-year RFS after Allo-SCT of pts who received PONA prophylaxis was 95%, and it was 57% for those who received PONA pre-emptively (log-rank p = 0.02). In conclusion, this multicenter analysis of 48 patients with Ph + ALL undergoing Allo-SCT while in CcR, although with the caution of the retrospective data, supports the feasibility of PONA maintenance strategy after Allo-SCT with a low rate of discontinuations (10.5%) due to PONA-related AE. Full article

(This article belongs to the Special Issue Hematopoietic Stem Cell Transplant in Hematological Malignancies)

19 pages, 3144 KiB

Open AccessArticle

High-Risk Genotypes of Human Papillomavirus at Diverse Anogenital Sites among Chinese Women: Infection Features and Potential Correlation with Cervical Intraepithelial Neoplasia

by Chao Zhao, Jiahui An, Mingzhu Li, Jingran Li, Yun Zhao, Jianliu Wang, Heidi Qunhui Xie and Lihui Wei

Cancers 2024, 16(11), 2107; https://doi.org/10.3390/cancers16112107 (registering DOI) - 31 May 2024

Abstract

Background: Both cervical cancer and cervical intraepithelial neoplasia (CIN) are associated with human papillomavirus (HPV) infection at different anogenital sites, but the infection features of high-risk (HR) HPVs at these sites and their association with cervical lesions have not been well characterized. Given [...] Read more.

Background: Both cervical cancer and cervical intraepithelial neoplasia (CIN) are associated with human papillomavirus (HPV) infection at different anogenital sites, but the infection features of high-risk (HR) HPVs at these sites and their association with cervical lesions have not been well characterized. Given the limitation of cervical HPV 16/18 test in screening patients with high-grade CIN (CIN 2+), studies on whether non-16/18 HR-HPV subtype(s) have potential as additional indicator(s) to improve CIN 2+ screening are needed. Methods: The infection of 15 HR-HPVs in vulva, anus, vagina, and cervix of 499 Chinese women was analyzed, and CIN lesion-associated HR-HPV subtypes were revealed. Results: In addition to the well-known cervical-cancer-associated HPV 16, 52, and 58, HPV 51, 53, and 56 were also identified as high-frequency detected subtypes prevalently and consistently present at the anogenital sites studied, preferentially in multi-infection patterns. HPV 16, 52, 58, 56, and 53 were the top five prevalent subtypes in patients with CIN 2+. In addition, we found that cervical HPV 33/35/52/53/56/58 co-testing with HPV 16/18 might improve CIN 2+ screening performance. Conclusion: This study provided a new insight into HR-HPV screening strategy based on different subtype combinations, which might be used in risk stratification clinically. Full article

(This article belongs to the Special Issue Cervical Cancer: Screening and Treatment in 2024)

17 pages, 600 KiB

Open AccessArticle

Qualitative Classification of Late Systemic Symptoms in Head and Neck Cancer Survivors

by Poppy Schoenberg, Elizabeth Wulff-Burchfield, David Schlundt, Kemberlee Bonnet, Mary Dietrich and Barbara Murphy

Cancers 2024, 16(11), 2106; https://doi.org/10.3390/cancers16112106 - 31 May 2024

Abstract

Improved rates of cancer control have increased the head and neck cancer survivor population. Cancer survivorship clinics are not widely available in the USA, and longitudinal supportive care for patients undergoing multimodal therapy has not advanced at a pace commensurate with improvements in [...] Read more.

Improved rates of cancer control have increased the head and neck cancer survivor population. Cancer survivorship clinics are not widely available in the USA, and longitudinal supportive care for patients undergoing multimodal therapy has not advanced at a pace commensurate with improvements in cancer control. Consequently, a large head and neck cancer survivor population whose quality of life may be chronically and/or permanently diminished presently exists. This lack of awareness perpetuates under-recognition and under-investigation, leaving survivors’ (mostly detrimental) experiences largely uncharted. We conducted a qualitative exploration of survivors’ experiences, aiming to unpack the profound impact of late systemic symptoms on daily life, encompassing work, relationships, and self-identity in the head and neck cancer survivor community. The study included 15 remitted head and neck survivors, ≥12 months from their final treatment, who participated in semi-structured interviews conducted by a medical oncologist. Data analysis comprised qualitative thematic analysis, specifically inductive hierarchical linear modeling, enriched by a deductive approach of anecdotal clinical reporting. Results highlighted that 43.36% of all quotation material discussed in the interviews pertained to chronic emotion disturbance with significant implications for other domains of life. A central symptom cluster comprised impairments in mood/emotions, daily activity, and significant fatigue. Dysfunction in sleep, other medical conditions, and cognitive deficits comprised a secondary cluster. Physical dysfunctionality, encompassing pain, appetite, and eating, and alterations in experienced body temperature, constituted a tertiary cluster, and perhaps were surprisingly the least discussed symptom burden among head and neck cancer survivors. Symptoms causing heightened long-term survivor burden may be considered epiphenomenal to central physical dysfunctionality, albeit being presently the least represented in cancer survivor care programs. Moving forward, the development of targeted and multi-dimensional treatment programs that encompass physical, psychosocial, and spiritual domains are needed to increase clinical specificity and effective holistic long-term solutions that will foster a more compassionate and informed future of care for the cancer survivorship community. Full article

(This article belongs to the Special Issue Latest Advancements in Health-Related Quality of Life Research in Cancer Survivorship)

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20 pages, 873 KiB

Open AccessSystematic Review

MRI for Differentiation between HPV-Positive and HPV-Negative Oropharyngeal Squamous Cell Carcinoma: A Systematic Review

by Linda L. Chen, Iris Lauwers, Gerda Verduijn, Marielle Philippens, Renske Gahrmann, Marta E. Capala and Steven Petit

Cancers 2024, 16(11), 2105; https://doi.org/10.3390/cancers16112105 - 31 May 2024

Abstract

Human papillomavirus (HPV) is an important risk factor for oropharyngeal squamous cell carcinoma (OPSCC). HPV-positive (HPV+) cases are associated with a different pathophysiology, microstructure, and prognosis compared to HPV-negative (HPV−) cases. This review aimed to investigate the potential of magnetic resonance imaging (MRI) [...] Read more.

Human papillomavirus (HPV) is an important risk factor for oropharyngeal squamous cell carcinoma (OPSCC). HPV-positive (HPV+) cases are associated with a different pathophysiology, microstructure, and prognosis compared to HPV-negative (HPV−) cases. This review aimed to investigate the potential of magnetic resonance imaging (MRI) to discriminate between HPV+ and HPV− tumours and predict HPV status in OPSCC patients. A systematic literature search was performed on 15 December 2022 on EMBASE, MEDLINE ALL, Web of Science, and Cochrane according to PRISMA guidelines. Twenty-eight studies (n = 2634 patients) were included. Five, nineteen, and seven studies investigated structural MRI (e.g., T1, T2-weighted), diffusion-weighted MRI, and other sequences, respectively. Three out of four studies found that HPV+ tumours were significantly smaller in size, and their lymph node metastases were more cystic in structure than HPV− ones. Eleven out of thirteen studies found that the mean apparent diffusion coefficient was significantly higher in HPV− than HPV+ primary tumours. Other sequences need further investigation. Fourteen studies used MRI to predict HPV status using clinical, radiological, and radiomics features. The reported areas under the curve (AUC) values ranged between 0.697 and 0.944. MRI can potentially be used to find differences between HPV+ and HPV− OPSCC patients and predict HPV status with reasonable accuracy. Larger studies with external model validation using independent datasets are needed before clinical implementation. Full article

(This article belongs to the Special Issue Radiotherapy for Head and Neck Squamous Cell Carcinoma)

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20 pages, 3740 KiB

Open AccessReview

When DNA Mutations Interplay with Cellular Proliferation: A Narrative History of Theories of Carcinogenesis

by Laura El Nachef, Audrey Bouchet, Michel Bourguignon and Nicolas Foray

Cancers 2024, 16(11), 2104; https://doi.org/10.3390/cancers16112104 - 31 May 2024

Abstract

While cancer is one of the most documented diseases, how normal cells become cancerous is still debated. To address this question, in the first part of this review, we investigated the long succession of theories of carcinogenesis since antiquity. Initiated by Hippocrates, Aristotle, [...] Read more.

While cancer is one of the most documented diseases, how normal cells become cancerous is still debated. To address this question, in the first part of this review, we investigated the long succession of theories of carcinogenesis since antiquity. Initiated by Hippocrates, Aristotle, and Galen, the humoral theory interpreted cancer as an excess of acid, the black bile. The discovery of the circulation of blood by Harvey in 1628 destroyed the basis of the humoral theory but revived the spontaneous generation hypothesis which was also promoted by Aristotle. In 1859, the theory of microbes promoted by Pasteur demonstrated the irrelevance of this last theory and contributed to the emergence of the germ cancer theory, opposed to the cellular theory of cancer, in which cancer was supposed to be caused by microbes or transformed cells, respectively. These theories were progressively refined by the notions of initiation, promotion, and progression thanks to advances in mutagenesis and cellular proliferation. In the second part of this review, recent discoveries and paradigms in carcinogenesis, notably the role of the protein ATM, a major actor of the stress response involved in both mutagenesis and cellular proliferation, were discussed to better understand the current state of the art of carcinogenesis. Full article

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

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22 pages, 4740 KiB

Open AccessArticle

Standardized Digital Image Analysis of PD-L1 Expression in Head and Neck Squamous Cell Carcinoma Reveals Intra- and Inter-Sample Heterogeneity with Therapeutic Implications

by Eric Deuss, Cornelius Kürten, Lara Fehr, Laura Kahl, Stefanie Zimmer, Julian Künzel, Roland H. Stauber, Stephan Lang, Timon Hussain and Sven Brandau

Cancers 2024, 16(11), 2103; https://doi.org/10.3390/cancers16112103 - 31 May 2024

Abstract

For practical reasons, in many studies PD-L1 expression is measured by combined positive score (CPS) from a single tumor sample. This does not reflect the heterogeneity of PD-L1 expression in head and neck squamous cell carcinoma (HNSCC). We investigated the extent and relevance [...] Read more.

For practical reasons, in many studies PD-L1 expression is measured by combined positive score (CPS) from a single tumor sample. This does not reflect the heterogeneity of PD-L1 expression in head and neck squamous cell carcinoma (HNSCC). We investigated the extent and relevance of PD-L1 expression heterogeneity in HNSCC analyzing primary tumors and recurrences (LRs), as well as metastases. Tumor tissue from 200 HNSCC patients was immunohistochemically stained for PD-L1 and analyzed using image-analysis software QuPath v3.4 with multiple specimens per patient. CPS was ≥20 in 25.6% of primary tumors. Intra-tumoral heterogeneity led to a therapeutically relevant underestimation of PD-L1 expression in 28.7% of patients, when only one specimen per patient was analyzed. Inter-tumoral differences in PD-L1 expression between primary tumors and lymph node metastasis (LNM) or LR occurred in 44.4% and 61.5% (CPS) and in 40.6% and 50% of cases (TPS). Overall survival was increased in patients with CPS ≥ 1 vs. CPS < 1 in primary tumors and LNM (hazard ratio: 0.46 and 0.35; p < 0.005); CPS in LR was not prognostic. Our analysis shows clinically relevant intra- and inter-sample heterogeneity of PD-L1 expression in HNSCC. To account for heterogeneity and improve patient selection for immunotherapy, multiple sample analyses should be performed, particularly in patients with CPS/TPS < 1. Full article

(This article belongs to the Special Issue Current Status and Perspective of Immunotherapy for Head and Neck Squamous Cell Carcinoma)

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15 pages, 1198 KiB

Open AccessReview

Lymphomas of the Vulva: A Review of the MITO Rare Cancer Group

by Francescapaola Magazzino, Cynthia Aristei, Anna Passarelli, Antonio Pierini, Ugo De Giorgi, Ruby Martinello, Lavinia Domenici, Sandro Pignata, Giorgia Mangili and Gennaro Cormio

Cancers 2024, 16(11), 2102; https://doi.org/10.3390/cancers16112102 - 31 May 2024

Abstract

Since they are very rare tumors, lymphomas of the vulva are often not properly recognized. Patients with vulvar lymphoma are generally elderly and the classical manifestation of the disease is a vulvar mass. No significant age differences have been found between primary and [...] Read more.

Since they are very rare tumors, lymphomas of the vulva are often not properly recognized. Patients with vulvar lymphoma are generally elderly and the classical manifestation of the disease is a vulvar mass. No significant age differences have been found between primary and secondary lymphoma. To make a correct diagnosis, it is therefore necessary to use not only histological examination but also the genetic and molecular profile in order to establish optimal therapeutic management. Literature analysis confirm the good prognosis of this disease. Full article

(This article belongs to the Section Cancer Epidemiology and Prevention)

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17 pages, 625 KiB

Open AccessReview

Targeting Neoantigens in Pancreatic Ductal Adenocarcinoma

by Gurkaranjot Singh, Drew Kutcher, Rajeshwar Lally and Vikrant Rai

Cancers 2024, 16(11), 2101; https://doi.org/10.3390/cancers16112101 - 31 May 2024

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and is currently the third leading cause of cancer-related death in the United States after lung and colon cancer. PDAC is estimated to be the second leading cause of cancer-related death [...] Read more.

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and is currently the third leading cause of cancer-related death in the United States after lung and colon cancer. PDAC is estimated to be the second leading cause of cancer-related death by 2030. The diagnosis at a late stage is the underlying cause for higher mortality and poor prognosis after surgery. Treatment resistance to chemotherapy and immunotherapy results in recurrence after surgery and poor prognosis. Neoantigen burden and CD8+ T-cell infiltration are associated with clinical outcomes in PDAC and paucity of neoantigen-reactive tumor-infiltrating lymphocytes may be the underlying cause for treatment resistance for immunotherapy. This suggests a need to identify additional neoantigens and therapies targeting these neoantigens to improve clinical outcomes in PDAC. In this review, we focus on describing the pathophysiology, current treatment strategies, and treatment resistance in PDAC followed by the need to target neoantigens in PDAC. Full article

(This article belongs to the Special Issue Current Clinical Studies of Pancreatic Ductal Adenocarcinoma)

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17 pages, 1236 KiB

Open AccessArticle

Implementation of HER2 Testing in Endometrial Cancer, a Summary of Real-World Initial Experience in a Large Tertiary Cancer Center

by Anna Plotkin, Ekaterina Olkhov-Mitsel, Weei-Yuarn Huang and Sharon Nofech-Mozes

Cancers 2024, 16(11), 2100; https://doi.org/10.3390/cancers16112100 - 31 May 2024

Abstract

HER2-targeted therapies have transformed the management of advanced or recurrent serous endometrial cancer (EC), leading to an increased clinical demand for HER2 testing. Despite its adoption in select academic centers, the global extent of such tumor testing is unclear. In this study, we [...] Read more.

HER2-targeted therapies have transformed the management of advanced or recurrent serous endometrial cancer (EC), leading to an increased clinical demand for HER2 testing. Despite its adoption in select academic centers, the global extent of such tumor testing is unclear. In this study, we report on the initial two-year experience of HER2 testing at a major academic center with a reference gynecologic oncology service and biomarker reference laboratory. All patients who underwent HER2 testing based on physician discretion, reflex HER2 testing, and reference laboratory requests were included. From February 2021 to October 2023, HER2 testing was performed on 192 tumor tissue samples from 180 EC patients. Serous carcinoma constituted 52% of samples, reflecting diagnostic challenges and limited therapeutic options for advanced EC. HER2 positivity was found in 28% of all cases and 30% of p53-aberrant cases. An immunohistochemistry (IHC) score of 3+ was found in 15% of samples, while IHC 2+ was found in 45% (13% IHC 2+/ISH+ and 32% IHC 2+/ISH−). The newly identified ‘HER2-low’ category comprised 46% of the samples. Heterogeneity was noted in 42% of HER2-positive cases, with complex patterns in 3%. NGS and HER2 IHC-FISH showed a 24% discordance, attributed to intratumoral heterogeneity, tumor cellularity, a small number of amplified cells, and the HER2/CEP17 ratio near the cut-off. This study offers real-world insights into HER2 testing in EC, highlighting the challenges and underscoring the need for standardized guidelines in specimen handling, proficiency testing, and scoring criteria to enhance patient management and therapeutic decision-making. Full article

(This article belongs to the Special Issue Endometrial Cancer: Old Questions and New Perspectives (Volume II))

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12 pages, 1517 KiB

Open AccessArticle

No Indication for Routine Resection of Surgical Scars during Cytoreductive Surgery and HIPEC

by Malin Enblad, Lana Ghanipour, Peter Cashin, Helgi Birgisson and Wilhelm Graf

Cancers 2024, 16(11), 2099; https://doi.org/10.3390/cancers16112099 - 31 May 2024

Abstract

Background: Careful macroscopic assessment of surgical scars is needed to avoid routine scar resection during cytoreductive surgery (CRS) for peritoneal metastases (PM). This study aimed to analyze the correlation between macroscopically suspected and microscopically confirmed scar metastases (SMs), and to analyze the prognostic [...] Read more.

Background: Careful macroscopic assessment of surgical scars is needed to avoid routine scar resection during cytoreductive surgery (CRS) for peritoneal metastases (PM). This study aimed to analyze the correlation between macroscopically suspected and microscopically confirmed scar metastases (SMs), and to analyze the prognostic impact of not undergoing routine scar resection. Method: All patients with previous surgery, treated with CRS and hyperthermic intraperitoneal chemotherapy, for colorectal PM or pseudomyxoma peritonei (PMP), at Uppsala University Hospital in 2013–2021, were included. Macroscopic SMs in surgical reports were compared with histopathological analyses. Results: In total, 227 patients were included. Among colorectal PM patients (n = 156), SM was macroscopically suspected in 41 (26%) patients, and 63 (40%) underwent scar resection. SM was confirmed in 19 (30%). Among patients with macroscopic suspicion, 45% had confirmed SM (positive predictive value, PPV). A total of 1 of 23 (4%) patients with no macroscopic suspicion had SM (negative predictive value, NPV = 96%). Among the PMP patients (n = 71), SM was macroscopically suspected in 13 (18%), and 28 (39%) underwent scar resection, of whom 12 (43%) had SM. The PPV was 77%. Occult SM was found in 1 of 14 (NPV = 93%). Not undergoing routine scar resection did not affect recurrence-free survival (RFS, p = 0.2) or overall survival (OS, p = 0.1) in colorectal PM patients or PMP patients (RFS p = 0.7, OS p = 0.7). Conclusion: Occult SM is uncommon and scar resection does not affect RFS or OS. Therefore, macroscopically benign-appearing scars can be left without resection, though resection should be performed upon suspicion or uncertainty. Full article

(This article belongs to the Section Cancer Metastasis)

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