Current Oncology

Malignant melanoma (MM) represents the most life-threatening skin cancer worldwide, with a narrow and inefficient chemotherapeutic arsenal available in advanced disease stages. Lupeol (LUP) is a triterpenoid-type phytochemical possessing a broad spectrum of pharmacological properties, including a potent anticancer effect against several neoplasms (e.g., colorectal, lung, and liver). However, its potential as an anti-melanoma agent has been investigated to a lesser extent. The current study focused on exploring the impact of LUP against two human MM cell lines (A375 and RPMI-7951) in terms of cell viability, confluence, morphology, cytoskeletal distribution, nuclear aspect, and migration. Additionally, the in ovo antiangiogenic effect has been also examined. The in vitro results indicated concentration-dependent and selective cytotoxicity against both MM cell lines, with estimated IC₅₀ values of 66.59 ± 2.20 for A375, and 45.54 ± 1.48 for RPMI-7951, respectively, accompanied by a reduced cell confluence, apoptosis-specific nuclear features, reorganization of cytoskeletal components, and inhibited cell migration. In ovo, LUP interfered with the process of angiogenesis by reducing the formation of neovascularization. Despite the potential anti-melanoma effect illustrated in our in vitro-in ovo study, further investigations are required to elucidate the underlying LUP-induced effects in A375 and RPMI-7951 MM cells. Full article

Brain parenchyma infiltration with glioblastoma (GB) cannot be entirely visualized by conventional magnetic resonance imaging (MRI). The aim of this study was to investigate changes in the energy and membrane metabolism measured with phosphorous MR spectroscopy (31P-MRS) in the presumably “normal-appearing” brain following chemoradiation therapy (CRT) in GB patients in comparison to healthy controls. Twenty (seven female, thirteen male) GB patients underwent a 31P-MRS scan prior to surgery (baseline) and after three months of standard CRT (follow-up examination. The regions of interest “contrast-enhancing (CE) tumor” (if present), “adjacent to the (former) tumor”, “ipsilateral distant” hemisphere, and “contralateral” hemisphere were compared, differentiating between patients with stable (SD) and progressive disease (PD). Metabolite ratios PCr/ATP, Pi/ATP, PCr/Pi, PME/PDE, PME/PCr, and PDE/ATP were investigated. In PD, energy and membrane metabolism in CE tumor areas have a tendency to “normalize” under therapy. In different “normal-appearing” brain areas of GB patients, the energy and membrane metabolism either “normalized” or were “disturbed”, in comparison to baseline or controls. Differences were also detected between patients with SD and PD. 31P-MRS might contribute as an additional imaging biomarker for outcome measurement, which remains to be investigated in a larger cohort. Full article

Background: Colorectal cancer is one of the most common malignancies in the Western world, and is responsible for about 10% of annual cancer-related deaths. Especially for UICC stage IV, the probability of survival is significantly reduced. Little is known about risk factors for specific metastatic patterns of colorectal cancer that may also influence patients’ overall survival. Methods: We used data from the IQVIA oncology dynamics (OD) database to determine the prevalence of pulmonary metastases in 19,321 patients with UICC stage IV colorectal cancer in eight European and Asian countries. Results: In total, 6132 of 19,321 (31.7%) study patients had lung metastases, with a higher prevalence among patients with rectal (37.5%) than colon (30.1%) cancer. When compared to China as the country with the lowest lung metastases prevalence, the odds for lung metastases were highest in UK (OR: 2.02, 95%CI: 1.80–2.28), followed by Italy (OR: 1.86, 95%CI: 1.52–2.27), Spain (OR: 1.85, 95%CI: 1.64–2.09), and Germany (OR: 1.47, 95%CI: 1.26–1.71). Conclusion: The prevalence of pulmonary metastases in UICC stage IV colorectal cancer varies widely among the different analyzed countries. Although the present data are purely descriptive, a possible combination of ethnic, environmental, and health care system-associated differences could be discussed as the underlying cause. Further studies are needed to investigate the reasons for differences in the prevalence of lung metastases. Full article

This study examines the association between rates of change in daily fruit and vegetable intake and in weekly levels of moderate-to-vigorous intensity physical activity (MVPA) over a 15-month period in women following primary treatment completion for breast cancer. Breast cancer survivors (N = 199) self-reported fruit and vegetable intake and wore an accelerometer for 7 consecutive days to measure levels of MVPA on five occasions every 3 months. Multivariate latent growth modeling revealed that the rate of change in fruit and vegetable intake was not associated with the rate of change in levels of MVPA. Baseline (Mean = 3.46 months post-treatment) levels of MVPA were not associated with the rate of change of daily fruit and vegetable intake; likewise, baseline fruit and vegetable intake was not associated with the rate of change in levels of MVPA. Behavioral interventions promoting fruit and vegetable intake should not be assumed to yield concomitant effects in promoting MVPA or vice versa. Full article

There have been significant advances in the treatment of metastatic renal cell carcinoma (mRCC), with immunotherapy (IO)-based combinations as the standard-of-care treatment in the front-line setting. IO in this setting is paired with another IO agent or with a vascular endothelial growth factor receptor (VEGF-R) tyrosine kinase inhibitor (TKI). One IO/IO combination and four IO/TKI combinations are currently approved. However, the role of the salvage IO in patients with disease progression on TKI monotherapy is uncertain. Here, we present a case series of five patients who were on single-agent TKI therapy for treatment-refractory mRCC and upon disease progression had an IO agent added to their TKI. The median duration of TKI monotherapy was 11.2 months (range, 1.7–31.1 months), and the median duration of response after the addition of IO was 4 months (range, 2.8–10.5 months). Although IO salvage therapy has a plausible rationale, this case series did not show a clear benefit to this approach. Further clinical trials are needed to determine the clinical utility of IO salvage therapy in mRCC. Full article

Aim of the study: To assess the occurrence of cardiac arrhythmias caused by high doses of levothyroxine in patients with thyroid cancer with subclinical hyperthyroidism. Materials and Methods: This prospective study included 98 women divided into three groups according to plasma thyroid stimulating hormone (TSH) concentration: <0.1 µU/mL, 0.1–0.39 µU/mL, or 0.4–4.0 µU/mL (control group). All participants underwent laboratory tests and an electrocardiography (ECG) Holter test to assess their heart rate and the occurrence of arrhythmias. Statistical analysis assessed differences between groups in all clinical parameters and factors influencing the occurrence of arrhythmias. Results: There were no differences between groups in the maximum, average, or minimum heart rate or in the incidence of the studied cardiac arrhythmias. Heart rate in women with a TSH concentration of <0.1 µU/mL depended on age and the presence of arterial hypertension, and heart rate in women with a TSH concentration of 0.4–4.0 µU/mL depended on free triiodothyronine concentration and the presence of arterial hypertension; no relationship was identified for women with a TSH concentration of 0.1–0.39 µU/mL. One-way logistic regression analysis did not identify any factors influencing the occurrence of arrhythmias. Conclusions: While maintaining normal free triiodothyronine levels, the use of suppressive doses of levothyroxine after thyroidectomy for differentiated thyroid cancer does not induce clinically significant arrhythmias or affect average heart rate. None of the studied clinical parameters influenced the risk of arrhythmia. Full article

The goal of this study was to describe the variation in hospital-based diagnostic care activities for patients with symptomatology suspect for breast cancer in The Netherlands. Two cohorts were included: the ‘benign’ cohort (30,334 women suspected of, but without breast cancer) and the ‘malignant’ cohort (2236 breast cancer patients). Hospital-based financial data was combined with tumor data (malignant cohort) from The Netherlands Cancer Registry. Patterns within diagnostic pathways were analyzed. Factors influencing the number of visits and number of diagnostic care activities until diagnosis were identified in the malignant cohort with multivariable Cox and Poisson regression models. Compared to patients with benign diagnosis, patients with malignant disease received their diagnosis less frequently in one day, after an equal average number of hospital visits and higher average number of diagnostic activities. Factors increasing the number of diagnostic care activities were the following: lower age and higher cM-and cN-stages. Factors increasing the number of days until (malignant) diagnosis were as follows: higher BIRADS-score, screen-detected and higher cN-and cT-stages. Hospital of diagnosis influenced both number of activities and days to diagnosis. The diagnostic care pathway of patients with malignant disease required more time and diagnostic activities than benign disease and depends on hospital, tumor and patient characteristics. Full article

Robot-assisted radical cystectomy (RARC) is replacing open radical cystectomy (ORC) and requires clamping of the ureters, resulting in a predisposition to postrenal acute kidney injury (AKI). We investigated the association between ureteral clamping or its duration and acute/chronic postoperative kidney function. Patients who underwent radical cystectomy (robotic or open) at two tertiary institutions during 2002–2021 were retrospectively enrolled. In those who underwent RARC, the maximum postoperative percentage serum creatinine level (%sCre) change was plotted against ureteral clamping duration. They were divided into two groups using the median clamping time (210 min), and the maximum %sCre change and percentage estimated glomerular filtration rate (%eGFR) change at 3–6 months (chronic) were compared between the ORC (no clamp), RARC < 210, and RARC ≥ 210 groups. In 44 RARC patients, a weak correlation was observed between the duration of ureteral clamping and %Cre change (R² = 0.22, p = 0.001). Baseline serum creatinine levels were comparable between the groups. However, %sCre change was significantly larger in the RARC ≥ 210 group (N = 17, +32.1%) than those in the RARC < 210 (N = 27, +6.1%) and ORC (N = 76, +9.5%) groups (both, p < 0.001). Chronic %eGFR change was comparable between the groups. Longer clamping of the ureter during RARC may precipitate AKI; therefore, the clamping duration should be minimized. Full article

CCNs are a specific type of matricellular protein, which are essential signaling molecules, and play multiple roles in multicellular eukaryotes. This family of proteins consists of six separate members, which exist only in vertebrates. The architecture of CCN proteins is multi-modular comprising four distinct modules. CCN Proteins achieve their primary functional activities by binding with several integrin7 receptors. The CCN family has been linked to cell adhesion, chemotaxis and migration, mitogenesis, cell survival, angiogenesis, differentiation, tumorigenesis, chondrogenesis, and wound healing, among other biological interactions. Breast cancer is the most commonly diagnosed cancer worldwide and CCN regulated breast cancer stands at the top. A favorable or unfavorable association between various CCNs has been reported in patients with breast carcinomas. The pro-tumorigenic CCN1, CCN2, CCN3, and CCN4 may lead to human breast cancer, although the anti-tumorigenic actions of CCN5 and CCN6 are also present. Several studies have been conducted on CCN proteins and cancer in recent years. CCN1 and CCN3 have been shown to exhibit a dual nature of tumor inhibition and tumor suppression to some extent in quiet recent time. Pharmacological advances in treating breast cancer by targeting CCN proteins are also reported. In our study, we intend to provide an overview of these research works while keeping breast cancer in focus. This information may facilitate early diagnosis, early prognosis and the development of new therapeutic strategies. Full article

The interventions used in cancer-survivorship care do not always address outcomes important to survivors. This study sought to understand stakeholders’ views on the key concerns of cancer survivors after treatment and the interventions needed to meet survivors’ and families’ psychosocial needs after completing cancer treatment. We conducted a descriptive qualitative study using semi-structured interviews with stakeholders (survivors, family/friend caregivers, oncology providers, primary care providers, and cancer system decision-/policy-makers) from across Canada. For the data analysis, we used techniques commonly employed in descriptive qualitative research, such as coding, grouping, detailing, and comparing the data. There were 44 study participants: 11 survivors, seven family/friend caregivers, 18 health care providers, and eight decision-/policy-makers. Stakeholder-relevant interventions to address survivors’ psychosocial needs were categorized into five groups, as follows: information provision, peer support, navigation, knowledge translation interventions, and caregiver-specific supports. These findings, particularly interventions that deliver timely and relevant information about the post-treatment period and knowledge translation interventions that strive to integrate effective tools and programs into survivorship care, have implications for future research and practice. Full article

Background: Individuals with psychiatric disorders (PD) have a high prevalence of tobacco use. Therefore, we assessed the hazard of receiving a tobacco-related (TR) cancer diagnosis among individuals with PD. Methods: Several population-based provincial databases were used to identify individuals in BC diagnosed with depression, schizophrenia, bipolar disorder, anxiety disorders, or multiple PD between 1990 and 2013. A primary population proxy comparison group (appendicitis) was also identified and matched to the psychiatric cohort based on age at cohort entry, gender, year of cohort entry, and postal code. We linked individuals in the cohort and comparison groups with the BC Cancer Registry. Using a competing risks approach, we estimated the effect of having a PD on the risk of receiving a TR cancer diagnosis, in light of the competing risk of mortality. Results: In total, 165,289 patients were included. Individuals with depression (HR = 0.81; p < 0.01; 95% CI: 0.73–0.91), anxiety disorders (HR = 0.84; p = 0.02; 95% CI: 0.73–0.97), or multiple PD (HR = 0.74; p < 0.01; 95% CI: 0.66–0.83) had a statistically significant lower risk of a TR cancer diagnosis compared to the comparison group. Individuals with schizophrenia (HR = 0.86; p = 0.40; 95% CI: 0.62–1.21) or bipolar disorder (HR = 0.58; p = 0.12; 95% CI: 0.29–1.14), however, showed no evidence of a statistically significant difference from the comparison group. Interpretation: We found that individuals with depression, anxiety disorders, or multiple PD diagnoses had a significantly reduced risk of receiving a tobacco-related cancer diagnosis. These results were unexpected and could be explained by individuals with a PD having barriers to a cancer diagnosis rather than a true decreased incidence. Full article

Colorectal cancer (CRC) is a leading cause of morbidity and mortality in Canada. CRC screening and other factors associated with early-stage disease can improve CRC treatment efficacy and survival. This study examined factors associated with CRC stage at diagnosis among male and female adults using data from a large prospective cohort study in Alberta, Canada. Baseline data were obtained from healthy adults aged 35–69 years participating in Alberta’s Tomorrow Project. Factors associated with CRC stage at diagnosis were evaluated using Partial Proportional Odds models. Analyses were stratified to examine sex-specific associations. A total of 267 participants (128 males and 139 females) developed CRC over the study period. Among participants, 43.0% of males and 43.2% of females were diagnosed with late-stage CRC. Social support, having children, and caffeine intake were predictors of CRC stage at diagnosis among males, while family history of CRC, pregnancy, hysterectomy, menopausal hormone therapy, lifetime number of Pap tests, and household physical activity were predictive of CRC stage at diagnosis among females. These findings highlight the importance of sex differences in susceptibility to advanced CRC diagnosis and can help inform targets for cancer prevention programs to effectively reduce advanced CRC and thus improve survival. Full article

Surgeries for gastrointestinal tract malignancies are based on the paradigm that we should remove the tumour together with its lymphatic drainage in one block. This concept was initially proposed in rectal surgery and called a total mesorectal excision. This procedure gained much interest and has improved oncological results in rectal cancer surgery. The same idea for mesogastric and complete mesogastric excisions was proposed but, because of the complexity of the gastric mesentery, it has not become a standard technique. In this review, we analysed anatomical and embryological factors, proposed technical aspects of this operation and incorporated the available initial results of this concept. We also discussed analogies to other gastrointestinal organs, as well as challenges to this concept. Full article

In the era of rapid development of new, expensive cancer therapies, value frameworks have been developed to quantify clinical benefit (CB). We assessed the evolution of CB since the 2015 introduction of The American Society of Clinical Oncology and The European Society of Medical Oncology value frameworks. Randomized clinical trials (RCTs) assessing systemic therapies for solid malignancies from 2010 to 2020 were evaluated and CB (Δ) in 2010–2014 (pre-value frameworks (PRE)) were compared to 2015–2020 (POST) for overall survival (OS), progression-free survival (PFS), response rate (RR), and quality of life (QoL). In the 485 studies analyzed (12% PRE and 88% POST), the most common primary endpoint was PFS (49%), followed by OS (20%), RR (12%), and QoL (6%), with a significant increase in OS and decrease in RR as primary endpoints in the POST era (p = 0.011). Multivariable analyses revealed significant improvement in ΔOS POST (OR 2.86, 95% CI 0.46 to 5.26, p = 0.02) while controlling for other variables. After the development of value frameworks, median ΔOS improved minimally. The impact of value frameworks has yet to be fully realized in RCTs. Efforts to include endpoints shown to impact value, such as QoL, into clinical trials are warranted. Full article

Colorectal cancer (CRC) has an important bearing (top five) on cancer incidence and mortality in the world. The etiology of sporadic CRC is related to the accumulation of genetic and epigenetic alterations that result in the appearance of cancer hallmarks such as abnormal proliferation, evasion of immune destruction, resistance to apoptosis, replicative immortality, and others, contributing to cancer promotion, invasion, and metastasis. It is estimated that, each year, at least four million people are diagnosed with CRC in the world. Depending on CRC staging at diagnosis, many of these patients die, as CRC is in the top four causes of cancer death in the world. New and improved screening tests for CRC are needed to detect the disease at an early stage and adopt patient management strategies to decrease the death toll. The three pillars of CRC screening are endoscopy, radiological imaging, and molecular assays. Endoscopic procedures comprise traditional colonoscopy, and more recently, capsule-based endoscopy. The main imaging modality remains Computed Tomography (CT) of the colon. Molecular approaches continue to grow in the diversity of biomarkers and the sophistication of the technologies deployed to detect them. What started with simple fecal occult blood tests has expanded to an armamentarium, including mutation detection and identification of aberrant epigenetic signatures known to be oncogenic. Biomarker-based screening methods have critical advantages and are likely to eclipse the classical modalities of imaging and endoscopy in the future. For example, imaging methods are costly and require highly specialized medical personnel. In the case of endoscopy, their invasiveness limits compliance from large swaths of the population, especially those with average CRC risk. Beyond mere discomfort and fear, there are legitimate iatrogenic concerns associated with endoscopy. The risks of perforation and infection make endoscopy best suited for a confirmatory role in cases where there are positive results from other diagnostic tests. Biomarker-based screening methods are largely non-invasive and are growing in scope. Epigenetic biomarkers, in particular, can be detected in feces and blood, are less invasive to the average-risk patient, detect early-stage CRC, and have a demonstrably superior patient follow-up. Given the heterogeneity of CRC as it evolves, optimal screening may require a battery of blood and stool tests, where each can leverage different pathways perturbed during carcinogenesis. What follows is a comprehensive, systematic review of the literature pertaining to the screening and diagnostic protocols used in CRC. Relevant articles were retrieved from the PubMed database using keywords including: “Screening”, “Diagnosis”, and “Biomarkers for CRC”. American and European clinical trials in progress were included as well. Full article

Uterine serous carcinoma accounts for 3–10% of endometrial cancers, but it is the most lethal histopathological subtype. The molecular characterization of endometrial carcinomas has allowed novel therapeutic approaches for these patients. We undertook a retrospective analysis of patients with uterine serous carcinomas treated in our hospital within the last two decades to identify possible changes in their management. The patients and their characteristics were evenly distributed across the two decades. Treatment modalities did not change significantly throughout this period. After adjuvant treatment, patients’ median disease-free survival was 42.07 months (95% CI: 20.28–63.85), and it did not differ significantly between the two decades (p = 0.059). The median overall survival was 47.51 months (95% Cl: 32.18–62.83), and it significantly favored the first decade’s patients (p = 0.024). In patients with de novo metastatic or recurrent disease, median progression-free survival was 7.8 months (95% Cl: 5.81–9.93), whereas both the median progression-free survival and the median overall survival of these patients did not show any significant improvement during the examined time period. Overall, the results of our study explore the minor changes in respect of uterine serous carcinoma’s treatment over the last two decades, which are reflected in the survival outcomes of these patients and consequently underline the critical need for therapeutic advances in the near future. Full article

High-intensity focused ultrasound (HIFU) is a novel advanced therapy for unresectable pancreatic cancer (PC). HIFU therapy with chemotherapy is being promoted as a novel method to control local advancement by tumor ablation. We evaluated the therapeutic effects of HIFU therapy in locally advanced and metastatic PC. PC patients were treated with HIFU as an optional local therapy and systemic chemotherapy. The FEP-BY02 (Yuande Bio-Medical Engineering) HIFU device was used under ultrasound guidance. Of 176 PC patients, 89 cases were Stage III and 87 were Stage IV. The rate of complete tumor ablation was 90.3%, while that of symptom relief was 66.7%. The effectiveness on the primary lesions were as follows: complete response (CR): n = 0, partial response (PR): n = 21, stable disease (SD): n = 106, and progressive disease (PD): n = 49; the primary disease control rate was 72.2%. Eight patients underwent surgery. The median survival time (MST) after diagnosis for HIFU with chemotherapy compared to chemotherapy alone (100 patients in our hospital) was 648 vs. 288 days (p < 0.001). Compared with chemotherapy alone, the combination of HIFU therapy and chemotherapy demonstrated significant prolongation of prognosis. This study suggests that HIFU therapy has the potential to be a novel combination therapy for unresectable PC. Full article

Information on the real-world experience of Canadians diagnosed with chronic lymphocytic leukemia (CLL) is limited. This study was conducted to report treatment patterns and outcomes of CLL using Ontario administrative data. A retrospective cohort study was conducted in patients diagnosed with CLL between 1 January 2010 and 31 December 2017 identified in the Ontario Cancer Registry (OCR). Data were accessed using the Institute of Clinical Evaluative Sciences (ICES), which collects various population-level health information. In the Ontario Cancer Registry, 2887 CLL patients receiving treatment and diagnosed between 2010–2017 were identified. Fludarabine, cyclophosphamide and rituximab (FCR) chemoimmunotherapy was most frequently used as a first line, but use declined since ibrutinib and obinutuzumab combinations were funded in 2015. In patients treated with frontline FCR, survival at year one was 89% pre-2015 and 96% post-2015; at year four, survival was 73% and 87%, respectively. Survival in patients treated with frontline chlorambucil was 76% pre-2015 and 75% post-2015 in year 1, and 45% and 56% in year 3. Our analysis shows that, as the treatment landscape for CLL has shifted, use of newer and novel agents as a first line or earlier in the relapsed/refractory setting has resulted in improved survival outcomes. Full article

Primary splenic lymphoma (PSL) is a rare malignancy representing about 1% of all lymphoproliferative disorders, when using a strict definition that allows only involvement of spleen and hilar lymph nodes. In contrast, secondary low-grade B-cell lymphomas in the spleen, such as follicular lymphomas (FL), lymphoplasmacytic lymphoma and chronic lymphocytic leukemia/ small lymphocytic lymphoma, particularly as part of advanced stage disease, are more common. Indolent B cell lymphomas expressing CD10 almost always represent FL, which in its primary splenic form is the focus of this review. Primary splenic follicular lymphoma (PSFL) is exceedingly infrequent. This type of lymphoproliferative disorder is understudied and, in most cases, clinically characterized by splenomegaly or cytopenias related to hypersplenism. The diagnosis requires correlation of histopathology of spleen, blood and/or bone marrow with the correct immunophenotype (determined by flow cytometry and/or immunohistochemistry) and if necessary, additional molecular profiling. Management of this incurable disease is evolving, and splenectomy remains the mainstream treatment for stage I PSFL. Full article