Cancers

17 pages, 863 KiB

Open AccessSystematic Review

by Luna Gauchez, Shannon Lauryn L. Boyle, Shinfu Selena Eekman, Sarah Harnie, Lore Decoster, Filip Van Ginderdeuren, Len De Nys and Nele Adriaenssens

Cancers 2024, 16(19), 3371; https://doi.org/10.3390/cancers16193371 (registering DOI) - 1 Oct 2024

Abstract

Background: This review aims to explore the role of physiotherapy in early and traditional palliative care (PC) for oncology patients, focusing on its impact on six patient-reported outcomes (PROMs), namely fatigue, pain, cachexia, quality of life (QoL), physical functioning (PHF), and psychosocial functioning [...] Read more.

Background: This review aims to explore the role of physiotherapy in early and traditional palliative care (PC) for oncology patients, focusing on its impact on six patient-reported outcomes (PROMs), namely fatigue, pain, cachexia, quality of life (QoL), physical functioning (PHF), and psychosocial functioning (PSF). The purpose is to assess the effectiveness of various physiotherapy interventions and identify gaps in the current research to understand their potential benefits in PC better. Methods: A systematic literature search was conducted across PubMed, Embase, and Web of Science, concluding on 21 December 2023. Two independent reviewers screened the articles for inclusion. The Cochrane Risk of Bias Tool 2 was employed to assess the risk of bias, while the GRADE approach was used to evaluate the certainty of the evidence. Results: Nine randomized controlled trials (RCTs) were included, with most showing a high risk of bias, particularly in outcome measurement and missing data. Cognitive behavioral therapy (CBT) was the only intervention that significantly reduced fatigue, enhanced PHF, and improved QoL and emotional functioning. Graded exercise therapy (GET) did not yield significant results. Combined interventions, such as education with problem-solving or nutritional counseling with physical activity, showed no significant effects. Massage significantly improved QoL and reduced pain, while physical application therapies were effective in pain reduction. Mindful breathing exercises (MBE) improved QoL but had a non-significant impact on appetite. The overall certainty of the evidence was low. Conclusions: Physiotherapy can positively influence PROMs in oncology PC; however, the low quality and high risk of bias in existing studies highlight the need for more rigorous research to confirm these findings and guide clinical practice. Full article

(This article belongs to the Special Issue Physiotherapy in Advanced Cancer and Palliative Care)

18 pages, 699 KiB

Open AccessReview

Telomere Length and Telomerase Activity as Potential Biomarkers for Gastrointestinal Cancer

by Christina Loukopoulou, Taxiarchis Nikolouzakis, Ioannis Koliarakis, Elena Vakonaki and John Tsiaoussis

Cancers 2024, 16(19), 3370; https://doi.org/10.3390/cancers16193370 - 1 Oct 2024

Abstract

Gastrointestinal (GI) cancers, such as colorectal and gastric cancers, pose significant global health challenges due to their high rates of incidence and mortality. Even with advancements in treatment and early detection, many patients still face poor outcomes, highlighting the critical need for new [...] Read more.

Gastrointestinal (GI) cancers, such as colorectal and gastric cancers, pose significant global health challenges due to their high rates of incidence and mortality. Even with advancements in treatment and early detection, many patients still face poor outcomes, highlighting the critical need for new biomarkers and therapeutic targets. Telomere length (TL) and telomerase activity (TA) have gained attention in this context. Telomeres, protective nucleotide sequences at chromosome ends, shorten with each cell division, leading to cellular aging. Telomerase, a ribonucleoprotein enzyme, counteracts this shortening by adding telomeric repeats, a process tightly regulated in normal cells but often dysregulated in cancer. This review critically evaluates the role of TL and TA in the pathogenesis of GI cancers, examining their potential as diagnostic, prognostic, and predictive biomarkers. It explores how alterations in telomere biology contribute to the initiation and progression of GI tumors and assesses the therapeutic implications of targeting telomerase. By integrating findings from diverse studies, this review aims to elucidate the intricate relationship between telomere dynamics and gastrointestinal carcinogenesis, offering insights into how TL and TA could be leveraged to enhance the early detection, treatment, and prognosis of GI cancers. Full article

(This article belongs to the Section Cancer Biomarkers)

14 pages, 333 KiB

Open AccessReview

Prostate-Specific Membrane Antigen-Positron Emission Tomography-Guided Radiomics and Machine Learning in Prostate Carcinoma

by Justine Maes, Simon Gesquière, Alex Maes, Mike Sathekge and Christophe Van de Wiele

Cancers 2024, 16(19), 3369; https://doi.org/10.3390/cancers16193369 - 1 Oct 2024

Abstract

Positron emission tomography (PET) using radiolabeled prostate-specific membrane antigen targeting PET-imaging agents has been increasingly used over the past decade for imaging and directing prostate carcinoma treatment. Here, we summarize the available literature data on radiomics and machine learning using these imaging agents [...] Read more.

Positron emission tomography (PET) using radiolabeled prostate-specific membrane antigen targeting PET-imaging agents has been increasingly used over the past decade for imaging and directing prostate carcinoma treatment. Here, we summarize the available literature data on radiomics and machine learning using these imaging agents in prostate carcinoma. Gleason scores derived from biopsy and after resection are discordant in a large number of prostate carcinoma patients. Available studies suggest that radiomics and machine learning applied to PSMA-radioligand avid primary prostate carcinoma might be better performing than biopsy-based Gleason-scoring and could serve as an alternative for non-invasive GS characterization. Furthermore, it may allow for the prediction of biochemical recurrence with a net benefit for clinical utilization. Machine learning based on PET/CT radiomics features was also shown to be able to differentiate benign from malignant increased tracer uptake on PSMA-targeting radioligand PET/CT examinations, thus paving the way for a fully automated image reading in nuclear medicine. As for prediction to treatment outcome following ¹⁷⁷Lu-PSMA therapy and overall survival, a limited number of studies have reported promising results on radiomics and machine learning applied to PSMA-targeting radioligand PET/CT images for this purpose. Its added value to clinical parameters warrants further exploration in larger datasets of patients. Full article

(This article belongs to the Special Issue Radiomics and Cancers)

18 pages, 1579 KiB

Open AccessReview

The Tumor Microenvironment as a Therapeutic Target in Cutaneous T Cell Lymphoma

by Louis Boafo Kwantwi, Steven T. Rosen and Christiane Querfeld

Cancers 2024, 16(19), 3368; https://doi.org/10.3390/cancers16193368 - 1 Oct 2024

Abstract

Cutaneous T cell lymphomas (CTCLs) are a heterogeneous group of non-Hodgkin lymphomas, with mycosis fungoides and Sézary syndrome being the two common subtypes. Despite the substantial improvement in early-stage diagnosis and treatments, some patients still progress to the advanced stage with an elusive [...] Read more.

Cutaneous T cell lymphomas (CTCLs) are a heterogeneous group of non-Hodgkin lymphomas, with mycosis fungoides and Sézary syndrome being the two common subtypes. Despite the substantial improvement in early-stage diagnosis and treatments, some patients still progress to the advanced stage with an elusive underpinning mechanism. While this unsubstantiated disease mechanism coupled with diverse clinical outcomes poses challenges in disease management, emerging evidence has implicated the tumor microenvironment in the disease process, thus revealing a promising therapeutic potential of targeting the tumor microenvironment. Notably, malignant T cells can shape their microenvironment to dampen antitumor immunity, leading to Th2-dominated responses that promote tumor progression. This is largely orchestrated by alterations in cytokines expression patterns, genetic dysregulations, inhibitory effects of immune checkpoint molecules, and immunosuppressive cells. Herein, the recent insights into the determining factors in the CTCL tumor microenvironment that support their progression have been highlighted. Also, recent advances in strategies to target the CTCL tumor micromovement with the rationale of improving treatment efficacy have been discussed. Full article

(This article belongs to the Special Issue Cutaneous T Cell Lymphomas: From Pathology to Treatment)

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17 pages, 4880 KiB

Open AccessArticle

Cytotoxic Autophagy: A Novel Treatment Paradigm against Breast Cancer Using Oleanolic Acid and Ursolic Acid

by Kunj Bihari Gupta, Jie Gao, Xin Li, Muthusamy Thangaraju, Siva S. Panda and Bal L. Lokeshwar

Cancers 2024, 16(19), 3367; https://doi.org/10.3390/cancers16193367 - 1 Oct 2024

Abstract

Background: Oleanolic acid (OA) and Ursolic acid (UA) are bioactive triterpenoids. Reported activities vary with the dose used for testing their activities in vitro. Studies using doses of ≥20 µM showed apoptosis activities in cancer cells. However, reported drug levels in circulation achieved [...] Read more.

Background: Oleanolic acid (OA) and Ursolic acid (UA) are bioactive triterpenoids. Reported activities vary with the dose used for testing their activities in vitro. Studies using doses of ≥20 µM showed apoptosis activities in cancer cells. However, reported drug levels in circulation achieved by oral administration of UA and OA are ≤2 µM, thus limiting their use for treatment or delivering a combination treatment. Materials and Methods: The present report demonstrates the efficacy of OA, UA, and OA + UA on tumor cell-specific cytotoxicity at low doses (5 µM to 10 µM) in breast cancer (BrCa) cell lines MCF7 and MDA-MB231. Results: The data show that both OA and UA killed BrCa cells at low doses, but were significantly less toxic to MCF-12A, a non-tumorigenic cell line. Moreover, OA + UA at ≤10 µM was lethal to BrCa cells. Mechanistic studies unraveled the significant absence of apoptosis, but their cytotoxicity was due to the induction of excessive autophagy at a OA + UA dose of 5 µM each. A link to drug-induced cytotoxic autophagy was established by demonstrating a lack of their cytotoxicity by silencing the autophagy-targeting genes (ATGs), which prevented OA-, UA-, or OA + UA-induced cell death. Further, UA or OA + UA treatment of BrCa cells caused an inhibition of PI3 kinase-mediated phosphorylation of Akt/mTOR, the key pathways that regulate cancer cell survival, metabolism, and proliferation. Discussion: Combinations of a PI3K inhibitor (LY294002) with OA, UA, or OA + UA synergistically inhibited BrCa cell survival. Therefore, the dominance of cytotoxic autophagy by inhibiting PI3K-mediated autophagy may be the primary mechanism of PTT-induced anticancer activity in BrCa cells. Conclusion: These results suggest it would be worthwhile testing combined OA and UA in clinical settings. Full article

(This article belongs to the Special Issue Anticancer Drug Discovery Based on Natural Products: From Computational Approaches to Clinical Studies)

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12 pages, 1087 KiB

Open AccessArticle

Impacts of Employment Status, Partnership, Cancer Type, and Surgical Treatment on Health-Related Quality of Life in Irradiated Head and Neck Cancer Survivors

by Ching-Rong Lin, Tsung-Min Hung, Eric Yi-Liang Shen, Ann-Joy Cheng, Po-Hung Chang, Shiang-Fu Huang, Chung-Jan Kang, Tuan-Jen Fang, Li-Ang Lee, Chih-Hung Chang and Joseph Tung-Chieh Chang

Cancers 2024, 16(19), 3366; https://doi.org/10.3390/cancers16193366 - 1 Oct 2024

Abstract

Objectives: This study aimed to examine the relationship between health-related quality of life (HRQoL) and sociodemographic and clinical variables in survivors of head and neck cancer (HNC) treated with radiotherapy, with or without surgery. Materials and Methods: HRQoL was measured using [...] Read more.

Objectives: This study aimed to examine the relationship between health-related quality of life (HRQoL) and sociodemographic and clinical variables in survivors of head and neck cancer (HNC) treated with radiotherapy, with or without surgery. Materials and Methods: HRQoL was measured using the functional assessment of cancer therapy—head and neck (FACT-H&N) in a cross-sectional survey involving 150 patients. Of these, 60 had nasopharyngeal cancer (NPC), treated exclusively with radiotherapy, while 90 had oral cavity squamous cell cancer (OSCC), undergoing radical surgery followed by adjuvant radiotherapy. Key variables included cancer type, age, gender, partnership status, education, and employment, with additional clinical variables assessed in patients with OSCC. Statistical analyses included multiple regression, ANOVA, and t-tests to explore relationships between variables and HRQoL. Results: Cancer type, surgical treatment, and employment status emerged as significant independent predictors of HRQoL in HNC patients. Patients with NPC reported better HRQoL on three FACT-H&N subscales—social/family well-being, functional well-being, and additional concerns—compared to patients with OSCC. Unemployed individuals exhibited lower HRQoL on four subscales. In patients with OSCC, partnership status and segmental mandibulectomy were found to predict HRQoL independently. Conclusions: This study concludes that cancer type, surgical intervention, and employment status notably influence HRQoL among HNC patients undergoing radiotherapy. In addition, partnership status is a key factor affecting HRQoL in patients with OSCC. Full article

(This article belongs to the Section Cancer Survivorship and Quality of Life)

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11 pages, 6012 KiB

Open AccessArticle

Perfusion Patterns of Peripheral Pulmonary Metastasis Using Contrast-Enhanced Ultrasound (CEUS) and Their Correlation with Immunohistochemically Detected Vascularization Pattern

by Johannes Kroenig, Christian Görg, Helmut Prosch, Lara Von Schumann, Christina C. Westhoff, Amjad Alhyari, Felix R. M. Koenig, Hajo Findeisen and Ehsan Safai Zadeh

Cancers 2024, 16(19), 3365; https://doi.org/10.3390/cancers16193365 - 1 Oct 2024

Abstract

Purpose: Description of the perfusion of pulmonary metastasis by contrast-enhanced ultrasound (CEUS) and their correlation with vascularization patterns represented by immunohistochemical CD34 endothelial staining. Patients and methods: The data of 54 patients with histologic proven peripheral pulmonary metastasis, investigated between 2004 and 2023 [...] Read more.

Purpose: Description of the perfusion of pulmonary metastasis by contrast-enhanced ultrasound (CEUS) and their correlation with vascularization patterns represented by immunohistochemical CD34 endothelial staining. Patients and methods: The data of 54 patients with histologic proven peripheral pulmonary metastasis, investigated between 2004 and 2023 by CEUS. These CEUS parameters were evaluated: time to enhancement (TE), categorized as early pulmonary-arterial (PA) or delayed bronchial-arterial (BA) patterns; extent of enhancement (EE), either marked or reduced; homogeneity of enhancement (HE), homogeneous or inhomogeneous; and decrease of enhancement (DE), rapid washout (<120 s) or late washout (≥120 s). Additionally, tissue samples in 45 cases (83.3%) were stained with CD34 antibody for immunohistochemical analysis. Results: In total, 4 lesions (7.4 %) exhibited PA enhancement, and 50 lesions (92.6%) demonstrated BA enhancement. Furthermore, 37 lesions (68.5%) showed marked enhancement, while 17 lesions (31.5%) exhibited reduced enhancement. The enhancement was homogeneous in 28 lesions (51.86%) and inhomogeneous in 26 lesions (48.14%). Additionally, 53 lesions (98.1%) displayed a rapid washout. A chaotic vascular pattern indicative of a bronchial arterial blood supply was identified in all cases (45/45, 100%), including all 4 lesions with PA enhancement. Conclusion: Pulmonary metastases in CEUS predominantly reveal bronchial arterial enhancement and a rapid washout. Regarding EE and HE, pulmonary metastases show heterogeneous perfusion patterns. A PA enhancement in CEUS does not exclude BA neoangiogenesis. Full article

(This article belongs to the Special Issue Advances in Lung Ultrasound in Cancer Patients)

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15 pages, 7564 KiB

Open AccessArticle

Gender-Specific Prognostic Impact of Treosulfan Levels in High-Dose Chemotherapy for Multiple Myeloma

by Alexander D. Heini, Karin Kammermann, Ulrike Bacher, Barbara Jeker, Michael Hayoz, Yolanda Aebi, Carlo R. Largiadèr, Henning Nilius and Thomas Pabst

Cancers 2024, 16(19), 3364; https://doi.org/10.3390/cancers16193364 - 1 Oct 2024

Abstract

Introduction: The growing body of evidence around sexual and gender dimorphism in medicine, particularly in oncology, has highlighted differences in treatment response, outcomes, and side effects between males and females. Differences in drug metabolism, distribution, and elimination, influenced by factors like body composition [...] Read more.

Introduction: The growing body of evidence around sexual and gender dimorphism in medicine, particularly in oncology, has highlighted differences in treatment response, outcomes, and side effects between males and females. Differences in drug metabolism, distribution, and elimination, influenced by factors like body composition and enzyme expression, contribute to these variations. Methods: We retrospectively analyzed data of 112 multiple myeloma (MM) patients treated with first-line high-dose chemotherapy (HDCT) with treosulfan and melphalan (TreoMel) followed by autologous stem cell transplantation (ASCT) at a single academic center between January 2020 and August 2022. We assessed response rate, progression-free survival (PFS), overall survival (OS), and toxicities in relation to gender and treosulfan exposure. Results: Our analysis revealed significant gender-specific differences in treosulfan exposure. Females had higher peak levels (343.8 vs. 309.0 mg/L, p = 0.0011) and area under the curve (AUC) (869.9 vs. 830.5 mg*h/L, p = 0.0427) compared to males. Higher treosulfan exposure was associated with increased mortality in females but not in males. Females with treosulfan AUC > 900 mg*h/L had significantly shorter overall survival, while PFS was unaffected by treosulfan exposure. Conclusion: Our study demonstrates that female patients undergoing TreoMel HDCT have higher treosulfan exposure than males and that females with higher levels are at increased risk for toxicity and adverse outcomes. These data suggest that higher treosulfan doses do not confer a benefit in terms of better outcomes for females. Therefore, exploring lower treosulfan doses for female MM patients undergoing TreoMel HDCT may be warranted to mitigate toxicity and improve outcomes. Full article

(This article belongs to the Special Issue Stem Cell Transplant and Cellular Therapies on Multiple Myeloma)

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14 pages, 463 KiB

Open AccessArticle

Prognostic Study of Colorectal Cancer: Differences between Screen-Detected and Symptom-Diagnosed Patients

by Sergio A. Novotny, Vidina A. Rodrigo Amador, Jordi Seguí Orejuela, Adriana López-Pineda, José A. Quesada, Avelino Pereira-Expósito, Concepción Carratalá-Munuera, Juan Hernandis Villalba and Vicente F. Gil-Guillén

Cancers 2024, 16(19), 3363; https://doi.org/10.3390/cancers16193363 - 30 Sep 2024

Abstract

Background and objective: Colorectal cancer (CRC) is the leading cause of mortality in Spain, with screening programs, such as the faecal occult blood test and colonoscopy, having shown effectiveness in reducing CRC incidence and mortality. Despite these advancements, CRC screening uptake remains low [...] Read more.

Background and objective: Colorectal cancer (CRC) is the leading cause of mortality in Spain, with screening programs, such as the faecal occult blood test and colonoscopy, having shown effectiveness in reducing CRC incidence and mortality. Despite these advancements, CRC screening uptake remains low in Spain, highlighting the need for studies comparing outcomes between screening-diagnosed and symptom-diagnosed patients to better understand the impact on overall survival and to quantify the clinical benefit in prognosis at diagnosis and at the end of follow-up. Methods: We conducted a retrospective cohort study with the following objectives: to compare stage at diagnosis, all-cause mortality, and disease-specific mortality among people diagnosed with CRC based on screening and based on symptoms; to identify the risk factors associated with mortality in this population; and to evaluate the effectiveness of screening on survival and early detection. Our study included people diagnosed with CRC in the public hospital of Elda (Spain) from 2014 to 2018; follow-up was until 2023 or death. Our primary outcome was all-cause mortality, which we analysed using Kaplan–Meier curves. We also investigated CRC-specific mortality and other-cause mortality. Results: Our sample included 315 people (186 with symptom-based diagnoses, 129 with screening-based diagnoses). The mean length of follow-up was 62.8 months. The screening group had a higher prevalence of a family history of CRC (p = 0.008), a distal tumour location (p = 0.002), and a cancer stage of 0 or I (p < 0.001). The symptoms group had a higher prevalence of a proximal CRC (p = 0.002), other chronic diseases (p < 0.001), and stages II, III, and IV (p < 0.001). Two variables were associated with mortality: stage IV at diagnosis and previous cancers. People with a symptom-based diagnosis had a higher prevalence of stage IV at diagnosis and a higher cumulative incidence of CRC mortality and all-cause mortality at the end of follow-up (p < 0.05). The Kaplan–Meier curves also showed a higher rate of all-cause mortality in the symptoms group throughout the follow-up. Conclusion: CRC screening enables an earlier diagnosis and improves survival. These findings support public health policies that promote accessible and effective screening. Full article

(This article belongs to the Special Issue Colorectal Cancer Awareness Month)

10 pages, 416 KiB

Open AccessArticle

The Association between Medroxyprogesterone Acetate Exposure and Meningioma

by Russell L Griffin

Cancers 2024, 16(19), 3362; https://doi.org/10.3390/cancers16193362 - 30 Sep 2024

Abstract

Background/Objectives: Medroxyprogesterone acetate (MPA) is a synthetic progesterone that is most commonly used as a contraceptive. MPA acts by binding to the progesterone receptor of the hypothalamus, and this receptor has been found to be important in the pathophysiology of meningiomas. Recent research [...] Read more.

Background/Objectives: Medroxyprogesterone acetate (MPA) is a synthetic progesterone that is most commonly used as a contraceptive. MPA acts by binding to the progesterone receptor of the hypothalamus, and this receptor has been found to be important in the pathophysiology of meningiomas. Recent research has reported an increased association between the use of MPA and intracranial meningioma, though the literature is mostly limited by low numbers of meningioma cases and low exposure to MPA. The objective of the current study is to build upon the previously published literature utilizing a large database from the United States. Methods: Utilizing a large commercial insurance database, the current matched case–control study identified meningioma cases using ICD-10 codes from hospital data and MPA exposure, as established from pharmaceutical claims data. Controls were matched 10:1 to cases based on age, year of enrollment, and duration of enrollment. A conditional logistic regression estimated odds ratios (ORs) for the association between MPA exposure and the odds of developing a meningioma. Results: Among 117,503 meningioma cases and 1,072,907 matched controls, oral MPA exposure was not associated with odds of meningioma; however, injection MPA exposure was associated with a 53% increased odds of being a case (OR 1.53, 95% CI 1.40–1.67). This association was specific to cerebral meningiomas (OR 1.68, 95% CI 1.50–1.87), an association that became stronger with a longer duration of use of injection MPA. Conclusions: The current results are consistent with the prior literature, which reports an association between injection exposures to MPA and a stronger association with increasing use of MPA. Women should be cautioned about the prolonged use of MPA, and future research should examine whether the extended use of MPA is associated with the meningioma grade. Full article

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

14 pages, 291 KiB

Open AccessReview

The Role of Maximal TURBT in Muscle-Invasive Bladder Cancer: Balancing Benefits in Bladder Preservation and Beyond

by Farshad Sheybaee Moghaddam, Sami Dwabe, Nataliya Mar, Leila Safdari, Navin Sabharwal, Hanan Goldberg, Michael Daneshvar and Arash Rezazadeh Kalebasty

Cancers 2024, 16(19), 3361; https://doi.org/10.3390/cancers16193361 - 30 Sep 2024

Abstract

Radical cystectomy with lymph node dissection and urinary diversion is the gold-standard treatment for non-metastatic muscle-invasive bladder cancer (MIBC). However, in patients who refuse cystectomy, or in whom cystectomy carries a high risk, bladder-preserving therapies remain potential options. Bladder preservation therapies can include [...] Read more.

Radical cystectomy with lymph node dissection and urinary diversion is the gold-standard treatment for non-metastatic muscle-invasive bladder cancer (MIBC). However, in patients who refuse cystectomy, or in whom cystectomy carries a high risk, bladder-preserving therapies remain potential options. Bladder preservation therapies can include maximal debulking transurethral resection of bladder tumor (TURBT), concurrent chemoradiation therapy, followed by cystoscopy to assess response. At this time, maximal TURBT is recommended for patients prior to the initiation of chemoradiation therapy or in patients with residual bladder tumors after the completion of chemoradiation therapy. That being said, TURBT carries significant risks such as bladder perforation, bleeding, and infection, ultimately risking delayed systemic treatment. Hence, understanding its role within trimodal therapy is crucial to avoid undue suffering in patients. Herein, we review the current literature on the impact of debulking TURBT in non-metastatic MIBC. Full article

(This article belongs to the Section Cancer Therapy)

14 pages, 865 KiB

Open AccessArticle

Tolerability and Safety Assessment of Adjuvant Chemoradiotherapy with S-1 after Limited Surgery for T1 or T2 Lower Rectal Cancer

by Norikatsu Miyoshi, Mamoru Uemura, Shingo Noura, Masayoshi Yasui, Junichi Nishimura, Mitsuyoshi Tei, Chu Matsuda, Shunji Morita, Akira Inoue, Hiroki Tamagawa, Yukako Mokutani, Shinichi Yoshioka, Makoto Fujii, Shinya Kato, Yuki Sekido, Takayuki Ogino, Hirofumi Yamamoto, Kohei Murata, Yuichiro Doki and Hidetoshi Eguchi

Cancers 2024, 16(19), 3360; https://doi.org/10.3390/cancers16193360 - 30 Sep 2024

Abstract

Background: The short-term outcomes of chemoradiotherapy (CRT) with S-1 (a combination of tegafur, gimeracil, and oteracil) following limited surgery for patients with T1 or T2 lower rectal cancer have shown encouraging results. Objectives: This study was designed to delve deeper into the long-term [...] Read more.

Background: The short-term outcomes of chemoradiotherapy (CRT) with S-1 (a combination of tegafur, gimeracil, and oteracil) following limited surgery for patients with T1 or T2 lower rectal cancer have shown encouraging results. Objectives: This study was designed to delve deeper into the long-term outcomes of CRT with S-1 after limited surgery, with the goal of evaluating both the long-term efficacy and potential risks associated with this treatment approach in patients diagnosed with T1 or T2 lower rectal cancer. Methods: This was conducted as a multicenter, single-arm, prospective phase II trial. The patient population consisted of individuals clinically diagnosed with either T1 or T2 lower rectal or anal canal cancer, with a maximum tumor diameter of 30 mm and classified as N0 or M0. Patients underwent local excision or endoscopic resection. After surgery, CRT with S-1 was administered to patients meeting several criteria, including the confirmation of well-differentiated or moderately differentiated adenocarcinoma, negative surgical margins, submucosal invasion depth of ≥1000 µm, and high tumor-budding grade (2/3). The primary endpoint of this study was relapse-free survival, while secondary endpoints included local recurrence-free survival, overall survival, anal sphincter preservation rate, and safety. Results: A total of 52 patients were included, with pathological diagnoses revealing T1 in 36 patients and T2 in 16 patients. The 3-year and 5-year relapse-free survival rates were 90.17% and 85.87%, respectively. The 3-year and 5-year local recurrence-free survival rates were 90.17% and 88.07%, respectively, while the 3-year and 5-year overall survival rates were 94.03% and 91.94%, respectively. Conclusions: CRT with S-1 after limited surgery for T1 lower rectal cancer demonstrated favorable outcomes in terms of recurrence, survival, and local control rates while effectively maintaining anal function in patients. However, further treatment approaches may be necessary to improve outcomes for patients diagnosed with stage T2 lower rectal cancer Full article

(This article belongs to the Special Issue The Survival of Colon and Rectal Cancer)

20 pages, 908 KiB

Open AccessReview

Histone Deacetylase Inhibitors for Peripheral T-Cell Lymphomas

by Ruxandra Irimia and Pier Paolo Piccaluga

Cancers 2024, 16(19), 3359; https://doi.org/10.3390/cancers16193359 - 30 Sep 2024

Abstract

Histone deacetylase inhibitors (HDACis) are being recognized as a potentially effective treatment approach for peripheral T-cell lymphomas (PTCLs), a heterogeneous group of aggressive malignancies with an unfavorable prognosis. Recent evidence has shown that HDACis are effective in treating PTCL, especially in cases where [...] Read more.

Histone deacetylase inhibitors (HDACis) are being recognized as a potentially effective treatment approach for peripheral T-cell lymphomas (PTCLs), a heterogeneous group of aggressive malignancies with an unfavorable prognosis. Recent evidence has shown that HDACis are effective in treating PTCL, especially in cases where the disease has relapsed or is resistant to conventional treatments. Several clinical trials have demonstrated that HDACis, such as romidepsin and belinostat, can elicit long-lasting positive outcomes in individuals with PTCLs, either when used alone or in conjunction with conventional chemotherapy. They exert their anti-tumor effects by regulating gene expression through the inhibition of histone deacetylases, which leads to cell cycle arrest, induction of programmed cell death, and,the transformation of cancerous T cells, as demonstrated by gene expression profile studies. Importantly, besides clinical trials, real-world evidence indicated that the utilization of HDACis presents a significant and beneficial treatment choice for PTCLs. However, although HDACis showed potential effectiveness, they could not cure most patients. Therefore, new combinations with conventional drugs as well as new targeted agents are under investigation. Full article

(This article belongs to the Special Issue Novel Targeted Therapies for T-cell Malignancies)

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10 pages, 241 KiB

Open AccessArticle

Short-Term Postoperative Outcomes after Resective Colorectal Surgery in Elderly vs. Nonelderly Patients: A Single Centre Retrospective Analysis

by Vincenzo Tondolo, Federica Marzi, Luca Emanuele Amodio and Gianluca Rizzo

Cancers 2024, 16(19), 3358; https://doi.org/10.3390/cancers16193358 - 30 Sep 2024

Abstract

Background/Objectives: Life expectancy for people in their 60s is 24.3 years in high-income countries. Health systems face the burden of disease in the elderly population and must assess the impact of treatments such as major surgery. The aim of this study is to [...] Read more.

Background/Objectives: Life expectancy for people in their 60s is 24.3 years in high-income countries. Health systems face the burden of disease in the elderly population and must assess the impact of treatments such as major surgery. The aim of this study is to quantify the impact of advanced age on short-term postoperative outcomes after resective colorectal surgery (RCRS). Methods: All patients who underwent RCRS at our institution between July 2022 and November 2023 were entered into a database. Preoperative, perioperative, and early (within 30 days) postoperative data were recorded. Patients were categorized into a young group (under 75 years, YG) and an elderly group (over 75 years, EG). A retrospective comparative analysis of postoperative outcomes was performed between the two groups; postoperative complications were graded according to the Clavien classification. Results: Fifty-three and ninety-five patients were in the EG and YG, respectively. Indications for RCRS was cancer in 83% of EG patients and 61.1% of YG patients (p = 0.006), and the clinical presentation, localization, and rate of neoadjuvant treatment in oncological patients were comparable. Another indication for RCRS was complicated diverticular disease (17% of EG patients and 38.9% of YG patients; p = 0.006). With respect to the baseline characteristics, the ASA and CCI scores were worse in the EG (p = 0.001). No significant differences in the surgical approach, mini-invasive approach, conversion rate, definitive stoma creation, or number of harvested lymph nodes were found between the two groups. Overall, EG reported a higher relative risk (RR) of short-term postoperative complications (1.64, CI: 1.03–2.63), but no significant differences were found in terms of grade ≥3 complications (RR: 0.9, CI: 0.23–3.44). In the EG, a higher risk of ICU admission (RR:2.69, CI: 1.5–4.8) and a one-day longer postoperative hospital stay (6 vs. 5 days) were reported. Conclusions: Advanced age does not seem to contraindicate RCRS, especially in colorectal cancer patients. The impact of elderly age on short-term outcomes seems to be minimal and acceptable. Full article

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

13 pages, 384 KiB

Open AccessReview

Modular Universal Tumor and Revision System Prostheses in Patients with Bone Cancer of the Lower Limbs: A Narrative Review of Functional Outcomes

by Paola E. Ferrara, Mariantonietta Ariani, Sefora Codazza, Adelaide Aprovitola, Daniele Polisano and Gianpaolo Ronconi

Cancers 2024, 16(19), 3357; https://doi.org/10.3390/cancers16193357 - 30 Sep 2024

Abstract

The optimal management of bone tumors requires a multidisciplinary strategy to guarantee high-quality care. At specialized centers, the medical team responsible for managing patients with bone cancer comprises oncologists, surgeons, radiologists, pathologists, and rehabilitation specialists. The goal of treatment is to achieve long-term [...] Read more.

The optimal management of bone tumors requires a multidisciplinary strategy to guarantee high-quality care. At specialized centers, the medical team responsible for managing patients with bone cancer comprises oncologists, surgeons, radiologists, pathologists, and rehabilitation specialists. The goal of treatment is to achieve long-term survival with minimal disability and pain. Postoperative rehabilitation is a fundamental therapeutic approach to enhance functionality and sustain the utmost quality of life following a limb-sparing surgery. Currently, megaprostheses are used for reconstructing bone defects after tumor resection, but in the literature, only a few studies have investigated rehabilitation outcomes in terms of functionality and impact on daily activities. This narrative review explores the functional and quality of life outcomes after the implantation of MUTARS^® prostheses in patients with lower extremity bone tumors. A comprehensive search was conducted on PubMed and Scopus using the following MESH terms: “MUTARS”, “Megaprosthesis”, “bone”, “tumors”, “metastasis”, “lower limb”, “rehabilitation”, “outcome”, and “quality of life”, and 10 studies were included. The most frequent oncological pathology was found to be primitive bone tumors treated with modular prostheses. The outcome measures used were the Henderson et al. classification, Harris Hip Scale, Musculoskeletal Tumor Society score, Visual Analog Scale, Range Of Motion, Karnofsky Performance Scale, and quality of life questionnaire. MUTARS^® is a well-established treatment option after bone tumor resection, although it involves extensive and complex post-resection reconstruction that exposes joints and tissues to substantial mechanical stress. Proper rehabilitation after MUTARS^® surgery is a fundamental therapeutic step, although there is still insufficient evidence in the literature focusing on functional and rehabilitative outcomes. Therefore, more studies and guidelines are needed to define standardized rehabilitation protocols for clinical practice after orthopedic oncologic surgery. Full article

(This article belongs to the Section Cancer Metastasis)

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20 pages, 3880 KiB

Open AccessSystematic Review

Prevalence of Sarcopenia Determined by Computed Tomography in Pancreatic Cancer: A Systematic Review and Meta-Analysis of Observational Studies

by Antonio Jesús Láinez Ramos-Bossini, Antonio Gámez Martínez, David Luengo Gómez, Francisco Valverde-López, Consolación Melguizo and José Prados

Cancers 2024, 16(19), 3356; https://doi.org/10.3390/cancers16193356 - 30 Sep 2024

Abstract

Introduction: Sarcopenia, a condition characterized by a loss of skeletal muscle mass, is increasingly recognized as a significant factor influencing patient outcomes in pancreatic cancer (PC). This systematic review and meta-analysis aimed to estimate the prevalence of sarcopenia in patients with PC using [...] Read more.

Introduction: Sarcopenia, a condition characterized by a loss of skeletal muscle mass, is increasingly recognized as a significant factor influencing patient outcomes in pancreatic cancer (PC). This systematic review and meta-analysis aimed to estimate the prevalence of sarcopenia in patients with PC using computed tomography and to explore how different measurement methods and cut-off values impact such prevalence. Materials and Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a comprehensive search of PubMed, Web of Science, and EMBASE databases was performed, identifying 48 observational studies involving 9063 patients. Results: The overall pooled prevalence of sarcopenia was 45% (95% CI, 40–50%), but varied significantly by the method used: 47% when measured with the skeletal muscle index and 33% when assessed with the total psoas area. In addition, in studies using SMI, sarcopenia prevalence was 19%, 45%, and 57% for cutoff values <40 cm²/m², 40–50 cm²/m², and >50 cm²/m², respectively. Moreover, the prevalence was higher in patients receiving palliative care (50%) compared to those treated with curative intent (41%). High heterogeneity was observed across all analyses, underscoring the need for standardized criteria in sarcopenia assessment. Conclusions: Our findings highlight the substantial variability in sarcopenia prevalence, which could influence patient outcomes, and stress the importance of consensus in measurement techniques to improve clinical decision making and research comparability. Full article

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

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13 pages, 973 KiB

Open AccessArticle

Nerve-Sparing Laparoscopic Radical Hysterectomy (nsLRH) without Adjuvant Therapy in FIGO Stage IB3 Cervical Cancer Patients: Surgical Technique and Survival Outcomes

by Roberto Tozzi, Sofia Bigardi, Giulia Spagnol, Federico Ferrari, Carlo Saccardi, Marco Noventa and Matteo Marchetti

Cancers 2024, 16(19), 3355; https://doi.org/10.3390/cancers16193355 - 30 Sep 2024

Abstract

(1) Background: In 2018 FIGO reclassified tumors confined to the cervix larger than 4 cm as stage IB3. Although concurrent CTRT has been the standard of care and surgery the alternative, optimal management remains controversial due to the lack of direct comparison between [...] Read more.

(1) Background: In 2018 FIGO reclassified tumors confined to the cervix larger than 4 cm as stage IB3. Although concurrent CTRT has been the standard of care and surgery the alternative, optimal management remains controversial due to the lack of direct comparison between surgery and CTRT. (2) Methods: This prospective observational study investigated the efficacy, safety and oncologic outcomes of nerve-sparing laparoscopic radical hysterectomy (nsLRH) for FIGO stage IB3 cervical cancer patients (IB3). From 2009 to 2023, IB3 patients underwent laparoscopic pelvic lymphadenectomies with frozen section analysis, followed by a nsLRH if the lymph nodes were tumor-free. No uterine manipulator was used and the vaginal cuff was sealed before retrieving the specimen. Intermediate-risk patients were under close observation without adjuvant therapy. Outcomes were monitored until 2023. (3) Results: During the study period, 74 IB3 patients were treated. Sixty-eight (91.9%) underwent a nsLRH. A complete resection with negative margins was achieved in all cases. At a median of 68 months of follow-up, the disease-free survival (DFS) rate was 89.7% and the overall survival (OS) rate was 93.1%. The overall complication rate was 23.5% and there were no grade 4–5 complications. (4) Conclusions: In patients with IB3 cervical cancer, a nsLRH is safe and effective. While awaiting the results from ongoing randomized trials, these findings support nsLRH as a viable treatment. Full article

(This article belongs to the Special Issue Cervical Cancer: Clinical Feature, Trial and Management)

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Graphical abstract

12 pages, 268 KiB

Open AccessReview

Comprehensive Axillary Management of Clinically Node-Positive (cN+) Breast Cancer Patients: A Narrative Review on Neoadjuvant Chemotherapy

by Calogero Cipolla, Vittorio Gebbia, Eleonora D’Agati, Martina Greco, Chiara Mesi, Giuseppa Scandurra and Maria Rosaria Valerio

Cancers 2024, 16(19), 3354; https://doi.org/10.3390/cancers16193354 - 30 Sep 2024

Abstract

Background. In breast cancer (BC) patients, axillary management has undergone major improvements over the last few years, and efforts to identify the optimal strategy for the management of axillary surgery are still ongoing. Methods. In current clinical practice, women with clinically node-positive (cN+) [...] Read more.

Background. In breast cancer (BC) patients, axillary management has undergone major improvements over the last few years, and efforts to identify the optimal strategy for the management of axillary surgery are still ongoing. Methods. In current clinical practice, women with clinically node-positive (cN+) BC usually receive neoadjuvant chemotherapy (NACT) with the aim of reducing the extent of primary disease and, thus, allowing for axillary-conservative surgery. Remarkably, after NACT, up to one out of three patients achieves an axillary pathologic complete response, which, in turn, is associated with a more favorable prognosis than residual axillary disease. However, NACT is not without drawbacks, as NACT-associated inflammation can damage lymphatic vessels. Furthermore, varying degrees of response may occur in the axillary lymph nodes, increasing the false negative rate for sentinel biopsy. Results. At present, there is no consensus on the optimal approach in patients with cN+ BC undergoing NACT, although multidisciplinary management seems to be recommended. Conclusions. This narrative review provides a comprehensive overview of axillary management in cN+ BC patients undergoing NACT. It uses a multidisciplinary approach that encompasses the oncological management perspectives, as well as surgical and chemotherapeutic viewpoints. Full article

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

15 pages, 2756 KiB

Open AccessArticle

Tumor Immune Microenvironment Biomarkers for Recurrence Prediction in Locally Advanced Rectal Cancer Patients after Neoadjuvant Chemoradiotherapy

by Jun-Eul Hwang, Sung-Sun Kim, Hyun-Jin Bang, Hyeon-Jong Kim, Hyun-Jeong Shim, Woo-Kyun Bae, Ik-Joo Chung, Eun-Gene Sun, Taebum Lee, Chan-Young Ock, Jeong-Seok Nam and Sang-Hee Cho

Cancers 2024, 16(19), 3353; https://doi.org/10.3390/cancers16193353 - 30 Sep 2024

Abstract

Background/Objectives: The tumor microenvironment (TME) has emerged as a significant prognostic factor. This study aimed to identify prognostic factors by combining clinicopathologic parameters and the TME biomarkers in patients who underwent surgery following neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC). Methods: [...] Read more.

Background/Objectives: The tumor microenvironment (TME) has emerged as a significant prognostic factor. This study aimed to identify prognostic factors by combining clinicopathologic parameters and the TME biomarkers in patients who underwent surgery following neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC). Methods: CD8⁺ T cells, CXCR3, CXCL10, and α-smooth muscle actin (α-SMA) were analyzed via immunohistochemical staining. We also incorporated AI-powered digital pathology to assess the spatial TME. The associations between these biomarkers, clinicopathologic parameters, and survival outcomes were evaluated. Results: CD8⁺ T cell expression, CXCR3 expression in tumor-infiltrating lymphocytes (TILs), and immune phenotypes were correlated. LARC patients with a high expression of CD8⁺ T cells, CXCR3 in TILs, and an inflamed phenotype had a significantly better prognosis than their counterparts did. In the multivariate analysis, the expression of CD8⁺ T cells and the inflamed/immune-excluded phenotype were significant tumor immune microenvironment (TiME) biomarkers for recurrence-free survival (RFS) but not for overall survival (OS). Notably, patients with the immune-desert phenotype had a poor prognosis regardless of pathologic stage, even if postoperative chemotherapy was administered (p < 0.001). Conclusions: CD8⁺ T cells and AI-powered immune phenotypes, alongside clinical factors, can guide personalized treatment in LARC patients receiving nCRT. A therapeutic strategy to modify the TiME after nCRT could help reduce recurrence after surgery. Full article

(This article belongs to the Special Issue The Role of Tumor Microenvironment in Solid Tumors: Development of Cancer Research)

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