Search

Abstract Highly selective inhibitors of cyclin-dependent kinase 4 and 6 (CDK4/6is) have emerged as a standart of care for first- and second-line therapies in combination with endocrine therapy (ET) for HR+/HER2- metastatic breast cancer (MBC) patients. It has been reported that combination therapy is more effective than ET alone and is safe in elderly patients as well as young patients. Nevertheless, elderly and very old patients with HR+/HER2-MBC treated with CDK4/6 inhibitor (CDK4/6i) combinations are relatively underrepresented in randomized controlled trials. To contribute to the literature, we investigated the real-world efficacy, factors associated with survival and the rates of adverse events (AEs) of the treatment with palbociclib or ribociclib plus ET in the HR+/HER2- MBC patient cohort over the age of 65 for age subgroups. In this retrospective study, 348 patients were divided into subgroups: 65–69 years old, 70–79 years old and 80 years and older. Median PFS (mPFS) for whole group was 18.3 (95% CI,14.3–22.3) months. There was no significant difference in mPFS between age groups (p = 0.75). The estimated median OS (mOS) was 39.5 (95% CI, 24.9–54.1) months and there was no significant difference between age groups (p = 0.15). There was a meaningfull numerical difference that did not reach statistical significance in patients who received CDK4/6i treatment as the first line for MBC. Grade 3–4 AEs were reported in 42.7% for the entire group, and neutropenia was the most common (37.3%). It can be concluded that combination therapy with palbociclib or ribociclib with an ET partner has similar efficacy and is safe among subgroups of older patients diagnosed with HR+/HER2-MBC.

Abstract Immune checkpoint inhibitors have revolutionized cancer treatment, but they are associated with a range of immune-related adverse events (irAEs), and emerging evidence suggests significant sex differences in the incidence, type, and severity of these toxicities, suggesting an influential factor and understanding sex-related differences in irAEs as crucial for optimizing patient care and improving clinical outcomes. In MOUSEION-07 study, we aimed to assess the association between sex and treatment-related adverse events in cancer patients treated with immunotherapy through a large up-to-date meta-analysis of available clinical trials. The present systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis. The protocol was registered with PROSPERO no. CRD42024549518. Sixteen studies encompassing a total of 4658 patients were included, and 2133 adverse effects were highlighted. The analysis observed a not statistically significant difference in terms of immune-related adverse events (irAEs) between males and females (Odds Ratio 1.19; CI 0.88–1.63) and revealed the presence of publication bias (β = −2.53; 95% CI = [−4.03; −1.04]; P = 0.006). Sex differences in immunotherapy-related adverse events are a significant factor in cancer treatment, necessitating a personalized approach to patient care. Further research is needed to fully understand the mechanisms driving these differences and to develop optimized strategies for monitoring and managing irAEs in both females and males.

Abstract Colorectal cancer (CRC) is the third most common cancer in the United States. Recent epidemiological evidence demonstrates an increasing incidence of young-onset CRC cases, defined as CRC cases in individuals 50 years old or younger. Studies have established that alterations in both the WNT and TGF-Beta signaling pathways have contributed to CRC development. While this is well understood, the comprehensive analysis of WNT and TGF-Beta pathway alterations in young-onset CRC cases has yet to be investigated. Here, we conducted a comprehensive bioinformatics analysis of mutations associated with each of the WNT and TGF-Beta signaling pathways according to age (≤ 50 years old versus > 50 years old) utilizing published genomic data from the cBioPortal. Chi-square results demonstrated no significant difference in WNT alterations between young-onset CRC and those > 50 years old. However, across all age groups, WNT alterations were frequently found in rectal cancers. We also found that WNT alterations were associated with better outcomes. The mutations associated with TGF-beta were observed at a higher rate in older CRC patients when compared to those ≤ 50 years old. Additionally, these mutations were found more frequently in colon primaries.

ABSTRACT Background Morphological and vascular characteristics of breast cancer can change during neoadjuvant chemotherapy (NAC). Dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI)‐acquired pre‐ and mid‐treatment quantitatively capture information about tumor heterogeneity as potential earlier indicators of pathological complete response (pCR) to NAC in breast cancer. Aims This study aimed to develop an ensemble deep learning‐based model, exploiting a Vision Transformer (ViT) architecture, which merges features automatically extracted from five segmented slices of both pre‐ and mid‐treatment exams containing the maximum tumor area, to predict and monitor pCR to NAC. Materials and Methods Imaging data analyzed in this study referred to a cohort of 86 breast cancer patients, randomly split into training and test sets at a ratio of 8:2, who underwent NAC and for which information regarding the pCR status was available (37.2% of patients achieved pCR). We further validated our model using a subset of 20 patients selected from the publicly available I‐SPY2 trial dataset (independent test). Results The performances of the proposed model were assessed using standard evaluation metrics, and promising results were achieved: area under the curve (AUC) value of 91.4%, accuracy value of 82.4%, a specificity value of 80.0%, a sensitivity value of 85.7%, precision value of 75.0%, F‐score value of 80.0%, and G‐mean value of 82.8%. The results obtained from the independent test show an AUC of 81.3%, an accuracy of 80.0%, a specificity value of 76.9%, a sensitivity of 85.0%, a precision of 66.7%, an F‐score of 75.0%, and a G‐mean of 81.2%. Discussion As far as we know, our research is the first proposal using ViTs on DCE‐MRI exams to monitor pCR over time during NAC. Conclusion Finally, the changes in DCE‐MRI at pre‐ and mid‐treatment could affect the accuracy of pCR prediction to NAC.

Background Immunotherapy has shown promise in treating various subtypes of metastatic cancers, but many patients are frail and may have compromised immune systems, which can influence treatment outcomes. Sarcopenia, a condition characterized by loss of muscle mass and systemic inflammation, is a potential factor that may negatively impact the response to immunotherapy. However, more data must be collected on the extent of its influence. Therefore, this study aims to investigate the effects of sarcopenia, systemic inflammation, and Eastern Cooperative Oncology Group Performance Status (ECOG PS) on the response to immunotherapy. Methods We enrolled 100 patients treated with immune checkpoint inhibitors between 2015 and 2021 who underwent computed tomography of the abdomen before the first immunotherapy dose. This study was conducted retrospectively. Gender-specific thresholds were used for the diagnosis of sarcopenia. C-reactive protein (CRP), erythrocyte sedimentation rate, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), albumin, and lactate dehydrogenase (LDH) were used as markers of systemic inflammation. Systemic inflammatory markers and sarcopenia were assessed using univariable and multivariable analyses for overall survival (OS) and progression-free survival (PFS). Results Sarcopenia was found to be a significant prognostic factor associated with poor PFS (HR, 2.33; 95% confidence interval [CI], 1.45-3.74; P < 0.001). In addition, hypoalbuminemia was identified as a significant prognostic factor for predicting OS (HR, 2.10; 95% CI, 1.21-3.66; P = 0.008). Conclusions Closer monitoring and prevention of sarcopenia may enhance both OS and PFS. Additionally, our composite model may assist oncologists in predicting responses to immunotherapy more accurately. However, further prospective studies are needed to validate these findings.

Aims: This study aimed to assess the habits and knowledge of cancer patients regarding the use of herbal medicines and dietary supplements in cancer patients receiving immune checkpoint inhibitors (ICI). Methods: The data of 181 cancer patients who were over 18 years old and received ICIs were collected. The usage patterns, anticipated benefits and harms, and sources of supply were evaluated by filling researcher-prepared forms. Results: Most patients did not use any kind of herbal medicine (91.2%) or dietary supplements (75.9%) during their immunotherapy. Boosting the immune system is the primary motivation for use among users. Multivitamins are the most frequently used supplements. Family members and TV advertisements were the main sources of information, in addition to limited advice from healthcare professionals. A minority of participants reported gastrointestinal side effects. Herbal medicine and dietary supplement use were more prevalent among patients with stage IV cancer and renal cell carcinoma (RCC). Discussion: This study revealed that the limited uptake of herbal medicines and dietary supplements alongside ICI treatment among cancer patients. The lack of adequate information from healthcare professionals poses potential risks to patients. Improved communication with patients, education regarding herbal medicine and dietary supplement use, potential interactions, and associated risks during ICI treatment are essential. Further research is needed to identify the specific needs of patients, anticipated benefits, and potential harms of herbal medicine and dietary supplement use, together with ICIs.

Abstract Non-Small cell lung cancer (NSCLC) is one of the most dangerous cancers, with 85% of all new lung cancer diagnoses and a 30–55% of recurrence rate after surgery. Thus, an accurate prediction of recurrence risk in NSCLC patients during diagnosis could be essential to drive targeted therapies preventing either overtreatment or undertreatment of cancer patients. The radiomic analysis of CT images has already shown great potential in solving this task; specifically, Convolutional Neural Networks (CNNs) have already been proposed providing good performances. Recently, Vision Transformers (ViTs) have been introduced, reaching comparable and even better performances than traditional CNNs in image classification. The aim of the proposed paper was to compare the performances of different state-of-the-art deep learning algorithms to predict cancer recurrence in NSCLC patients. In this work, using a public database of 144 patients, we implemented a transfer learning approach, involving different Transformers architectures like pre-trained ViTs, pre-trained Pyramid Vision Transformers, and pre-trained Swin Transformers to predict the recurrence of NSCLC patients from CT images, comparing their performances with state-of-the-art CNNs. Although, the best performances in this study are reached via CNNs with AUC, Accuracy, Sensitivity, Specificity, and Precision equal to 0.91, 0.89, 0.85, 0.90, and 0.78, respectively, Transformer architectures reach comparable ones with AUC, Accuracy, Sensitivity, Specificity, and Precision equal to 0.90, 0.86, 0.81, 0.89, and 0.75, respectively. Based on our preliminary experimental results, it appears that Transformers architectures do not add improvements in terms of predictive performance to the addressed problem.

Introduction: Although immune checkpoint inhibitors (ICIs) are widely used in cancer treatment, identifying factors that predict treatment response remains a challenge in clinical practice. There is a need for biomarkers to identify patients who may not benefit from these treatments. It is crucial to identify a simple and cost-effective biomarker that can be easily incorporated into clinical practice. This study aims to investigate the mean platelet volume to lymphocyte ratio (MPVLR), as measured by a hemogram test, and median overall survival (mOS) in patients with cancer treated with nivolumab. Methods: A total of 131 adult patients with metastatic cancer, including malignant melanoma (MM), renal cell carcinoma (RCC), non–small cell lung cancer (NSCLC), and head and neck cancer (HNC), were included in this study. Baseline demographics, ECOG (Eastern Cooperative Oncology Group) performance status, tumor type, and blood count parameters were recorded. Univariate and multivariate analyses were conducted to evaluate potential risk factors. Results: The median age of the patients was 59.87 ± 11.97 years, and the median follow-up period was 20.20 months (IQR, 12.80–27.60). RCC (43.5%) and MM (25.9%) were the most common diagnoses. Patients with ECOG scores of 0–1 had a longer mOS than those with scores of 2–3 (mOS: 20.60 months [95% CI, 14.94–25.29] vs. 5.24 months [95% CI, 0–16.42], p < 0.001). Additionally, patients with lactate dehydrogenase (LDH) levels within the normal range had a longer mOS than those with high LDH levels (mOS: 24.54 months [95% CI, 14.13–34.96] vs. 13.10 months [95% CI, 4.49–21.72], p = 0.038). Patients with low MPVLR also had a longer mOS than those with high MPVLR (mOS: 33.70 months [95% CI, 25.99–41.42] vs. 11.07 months [95% CI, 6.89–15.24], p < 0.001). In the multivariate Cox regression analysis, high MPVLR, ECOG score of 2–3, and high LDH level were associated with shorter mOS (p < 0.001, p = 0.001, and p = 0.046, respectively). Conclusion: This study demonstrates that MPVLR could serve as a novel biomarker for predicting response to nivolumab treatment. Incorporating MPVLR into clinical practice may aid in identifying patients who are less likely to benefit from the treatment.

Triple negative breast cancer (TNBC) represents the breast cancer subtype with least favorable outcome because of the lack of effective treatment options and its molecular features. Recently, ADCs have dramatically changed the breast cancer treatment landscape; the anti-TROP2 ADC Sacituzumab Govitecan has been approved for treatment of previously treated, metastatic TNBC patients. The novel ADC Datopotecan-deruxtecan (Dato-DXd) has recently shown encouraging results for TNBC. In the current paper, we summarize and discuss available data regarding this TROP-2 directed agent mechanism of action and pharmacologic activity, we describe first results on efficacy and safety of the drug and report characteristics, inclusion criteria and endpoints of the main ongoing clinical trials.

This study addresses the gap in understanding the prognostic relevance of hypoxia-inducible factor-1 alpha (HIF-1 alpha) expression in metastatic cervical squamous cell carcinoma (SCC) patients undergoing anti-vascular endothelial growth factor-based therapy. A retrospective multicenter study (n = 34) explored HIF-1 alpha expression via immunohistochemistry in patients treated with platinum chemotherapy and bevacizumab. Median progression-free survival (PFS) was significantly lower in the HIF-1 alpha low score group compared to the high score group (4.9 vs 12.9 months, P = 0.014). Similarly, the median overall survival (OS) was significantly reduced in the HIF-1 alpha low score group (8.3 vs 20.4 months, P = 0.006). This study, the first of its kind, highlights the prognostic significance of HIF-1 alpha expression in metastatic cervical SCC patients treated with bevacizumab-based therapy.

Abstract Introduction The advances in immune checkpoint inhibitors (ICIs) were relatively slow in rare tumors. Therefore, we conducted a multi‐center study evaluating the efficacy of ICI monotherapy and the combination of ICIs with chemotherapy (CT) in patients with advanced rare tumors. Methods In this retrospective cohort study, we included 93 patients treated with ICIs for NCI‐defined rare tumors from the 12 cancer centers in Turkey. The primary endpoints were the overall response (ORR) and disease control rate (DCR). Results The cohort's median age was 56, and 53.8% of the patients were male. The most frequent diagnosis was sarcoma (29%), and 81.7% of the patients were previously treated with at least one line of systemic therapy in the advanced stage. The ORR and DCR were 36.8% and 63.2%, respectively. The germ cell tumors had the lowest ORR (0%), while the Merkel cell carcinoma had the highest ORR to ICIs (57.1%). Patients treated with ICI + ICI or ICI plus chemotherapy combinations had higher ORR (55.2% vs. 27.6%, p = 0.012) and DCR (82.8% vs. 53.4%, p = 0.008). The median OS was 13.47 (95% CI: 7.79–19.15) months, and the six and 12‐month survival rates were 71% and 52%. The median duration of response was 16.59 months, and the 12‐month progression‐free survival rate was 66% in responders. The median time‐to‐treatment failure was 5.06 months (95% CI: 3.42–6.71). Three patients had high‐grade irAEs with ICIs (grade 3 colitis, grade 3 gastritis, and grade 3 encephalitis in one patient each). Conclusion We observed over 30% ORR and a 13‐month median OS in patients with rare cancers treated with ICI monotherapy or ICI plus CT combinations. The response rates to ICIs or ICIs plus CT significantly varied across different tumor types. Responding patients had over 2 years of survival, highlighting a need for further trials with ICIs for patients with rare tumors.

Trastuzumab emtansine (T-DM1) is a mainstay therapy for HER2-positive metastatic breast cancer (mBC). However, identifying patients who will benefit most remains a challenge due to the lack of reliable biomarkers. The recently developed pan-immune-inflammation value (PIV), a novel immune-inflammation marker, could aid in this regard, considering the immunomodulatory effects of T-DM1. Therefore, we aimed to evaluate the association between the PIV and the efficacy of T-DM1 in patients with HER2-positive mBC. A total of 122 HER2-positive mBC patients treated with T-DM1 were included. Receiver operating characteristic (ROC) curve analyses were conducted to determine the optimal PIV threshold value for survival prediction. Kaplan–Meier survival curves and Cox regression analyses were used for univariable and multivariable survival analyses, respectively. The median age was 51 years, and 95.1% of the patients had ECOG PS 0-1. The optimal PIV cutoff value was identified as 338 in ROC analyses (AUC: 0.667, 95% CI: 0.569–0.765, p = 0.002). The multivariate analysis revealed that patients in the high-PIV group had significantly shorter OS (HR: 2.332; 95% CI: 1.408–3.861; p = 0.001) and PFS (HR: 2.423; 95% CI: 1.585–3.702; p < 0.001) than patients in the low-PIV group. Additionally, both ORR and DCR were significantly lower in the high-PIV group (36.6% vs. 61.3%, p = 0.011; 56.1% vs. 76.0%, p = 0.027). Our findings suggest that pre-treatment PIV may be a novel prognostic biomarker for HER2-positive mBC patients receiving T-DM1. A low PIV level is associated with more favorable outcomes. Future prospective studies are warranted to validate these findings and explore the potential utility of PIV in aiding treatment decisions.

Background: The albumin levels may potentially be used as a prognostic biomarker in patients with cancertreated with immune checkpoint inhibitors (ICIs) due to its close relationship with nutritional and inflammatory status. However, the available data is limited with heterogeneous patient cohorts, sample sizes and variable cut-offs. Therefore, we conducted a systematic review and meta-analysis to evaluate the association between survival outcomes and albumin levels in patients treated with ICIs.Methods: We conducted a systematic review using the PubMed, Web of Science, and Embase databases to filter the published studies up to 1 June 2022. The meta-analyses were performed with the generic inverse-variance method with a random-effects model due to the high degree of heterogeneity. The primary outcome measure was hazard ratio (HR) with 95% confidence intervals (CI). The study protocol was registered with the PROSPERO registry (Registration Number: CRD42022337746).Results: Thirty-six studies encompassing 8406 cancer patients with advanced disease were included in the meta-analyses. Almost half of the studies were conducted in NSCLC cohorts (n = 15), and 3.5 gr/dL was the most frequently used albumin cut-off in the included studies (n = 20). Patients with lower albumin levels had a significantly increased risk of death (HR: 1.65, 95% CI: 1.52–1.80, p < 0.0001) than patients with higher albumin levels. Subgroup analyses for study location, sample size, tumor type and albumin cut-off were demonstrated consistent results. Furthermore, in the subgroup analysis of eight studies using albumin levels as a continuous prognostic factor, every 1 gr/dL decrease in albumin levels was associated with significantly increased risk of death by a factor of 10% (HR: 1.10, 95% CI: 1.05–1.16, p = 0.0002). Similar to analyses with overall survival, the patients with lower albumin levels had an increased risk of progression or death compared to patients with higher albumin levels (HR: 1.76, 95% CI: 1.40–2.21, p < 0.001).Conclusion: The available evidence demonstrates that albumin levels may be a prognostic biomarker in advanced cancer patients treated with ICIs. Further research is needed to delineate the role of albumin levels in patients treated with ICIs in the adjuvant setting, as well as the possible benefit of therapeutic approaches to improve hypoalbuminemia.

Systemic treatments (e.g., chemotherapy and targeted therapies) have limited efficacy for patients with locally advanced – unresectable – and metastatic cholangiocarcinoma (CCA), with an overall survival of less than a year. Tumor microenvironment (TME) represents the ecosystem surrounding the tumor which comprises immune cells, fibroblasts, endothelial cells, and a wide range of soluble factors. CCA TME is characterized by an abundant desmoplastic stroma, exhibits a high heterogeneity and it plays a central role in cancer onset and progression. There is growing evidence suggesting that it is possible to target TME in association with other treatment modalities, such as cytotoxic chemotherapy or targeted therapies, paving the way to possible combination strategies with a synergistic effect. Herein, we describe the components of CCA TME – such as cancer-associated fibroblasts and other cells of pivotal importance - with their most relevant interactions, focusing on the preclinical rationale for the development of effective anticancer treatments.

Aim: Recently, three randomized controlled trials evaluated the addition of docetaxel to ADT in advanced hormone-sensitive prostate cancer (aHSPC). Interestingly, all trials showed a trend towards improved OS in the subgroup of patients with Gleason

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy and reshaped medical oncology practice over the past decade. However, despite unprecedented and durable clinical responses, most patients eventually fail to respond to ICI therapy due to primary or acquired resistance. There is a great need for complementary alternative medicine, such as botanicals and nutritional supplements, because of their capability to modulate a myriad of molecular mechanisms to prevent immunotherapy resistance and reduce its adverse effects. Mounting evidence suggests that phytochemicals, biologically active compounds derived from plants, can favorably regulate key signaling pathways involved in tumor development and progression. In addition, phytochemicals have been found to exert anticancer effects by altering the expression of checkpoint inhibitors of the immune response. The immunomodulatory activity of phytochemicals in the tumor microenvironment has recently received immense interest. Based on these immunomodulatory activities, phytochemicals could be candidates for combination with ICIs in future clinical studies. The current review focuses on the available evidence for combining phytochemicals with a discussion on the promising opportunities to enhance the efficacy of immune checkpoint inhibitors and potential challenges resulting from these combinations.

Coronavirus disease 2019 (COVID-19) is expected to significantly affect cancer patients due to adverse outcomes with COVID-19 and disruptions in cancer care. Another important point is the stress and anxiety burden of COVID-19, which could affect quality of life. Patient education is vital due to the vulnerability of the topic to disinformation. To determine the areas needing improvements in patient education, and coping with stress, the burden of the problem should be pictured. From this point, we aimed to assess the perspectives and fears of cancer patients about COVID-19 with resources of COVID-19 knowledge with a questionnaire. A total of 250 adult cancer patients applied to the outpatient chemotherapy unit of Hacettepe University Cancer Center between May 27, 2020, and June 9, 2020, invited to answer a questionnaire of 13 multiple-choice questions with a return rate of 78% (195/250). Most patients acquired their knowledge about COVID-19 from television (91.9%). Social media were the second most common source of knowledge (43.8%) with a predilection in younger patients, nonsmokers, targeted therapy- or immunotherapy-treated patients, and breast cancer patients (>65 vs.

Abstract Background Despite initial dramatic responses, metastatic small cell lung cancer (SCLC) invariably recurs. Irinotecan is one of the active agents for patients with recurrent SCLC. In the second line, weekly or three-weekly irinotecan regimens have been adopted, however, the optimal dose and schedule is not defined. In our institution, we use a bi-weekly regimen of irinotecan. In this study, we aimed to investigate the safety and efficacy of the bi-weekly irinotecan in the second- or third-line treatment of SCLC patients. Methods The study population consisted of advanced stage SCLC patients who were followed at Hacettepe University Cancer Institute between January 2007 and March 2021 and received salvage irinotecan 180 mg/m2 every two weeks, following progression after platinum-etoposide treatment. Results One hundred patients were included. At diagnosis, nineteen patients (19%) had limited stage and 81 patients (81%) had extensive stage SCLC. Objective response rates (ORR) were 44.6% and 46.2% for patients who received irinotecan treatment in second line, and in third line, respectively. Seventeen percent of all the patients had grade 3 and above adverse events during irinotecan treatment. In our study, 45.8% of patients were able to complete at least 6 cycles of irinotecan treatment and 69.8% were able to receive at least 3 cycles of irinotecan treatment without any dose interruption or reduction. Conclusions Irinotecan 180 mg/m2 every two weeks appears to be safe and effective in the 2nd- and 3rd-line treatment of advanced stage SCLC. Bi-weekly administration allows G-CSF prophylaxis in between doses, leading to an uninterrupted administration.