Critical reviews in oncology/hematology最新文献

Recent advancements in the treatment of osteosarcoma, a rare and aggressive form of bone cancer, have seen significant progress with chemotherapy, immunotherapy, and targeted therapy. Chemotherapy, the conventional approach, has witnessed refined drug regimens and novel agents tailored to enhance efficacy while minimizing adverse effects. This evolution aims to strike a balance between eradicating cancer cells and preserving patients' overall well-being. Immunotherapy has emerged as a promising avenue, leveraging the body's immune system to recognize and combat cancer cells. Innovative immunotherapeutic strategies, including immune checkpoint inhibitors, adoptive T cell therapy, and chimeric antigen receptor (CAR)-T cell therapy, exhibit the potential to enhance immune responses against osteosarcoma. Moreover, targeted therapy, designed to disrupt specific molecular pathways crucial for cancer growth, has gained traction in the treatment of osteosarcoma. Precision medicine approaches, such as identifying biomarkers and employing targeted agents, aim to tailor therapies to individual patients, maximizing effectiveness while minimizing collateral damage to healthy tissues. This article analyzes the current state of these three treatment modalities while comparing the efficacies of current chemotherapy, immunotherapy and targeted therapy agents.

Cancer is currently one of the biggest public health challenges worldwide, ranking as the second leading cause of death globally. To date, strong epidemiological associations have been demonstrated between unhealthy lifestyles and eating habits, i.e. obesity, and an increased risk of developing cancer. However, there is limited evidence regarding the impact of specific dietary regimes on cancer outcomes during conventional cancer treatments. This paper systematically reviews and evaluates preclinical and clinical evidence regarding the effects of fasting, fast-mimicking diet, ketogenic diet, vegan diet, alkaline diet, paleolithic diet, the Gerson regimen, and macrobiotic diet in the context of cancer treatments. Clinical trials on dietary regimes as complementary cancer therapy are limited by significant differences in trial design, patient characteristics, and cancer type, making it difficult to draw conclusions. In the future, more uniformly controlled clinical trials should help to better define the role of diets in cancer management.

BRAF p.V600E exon 15 hotspot mutation can identify a molecular subgroup of metastatic colorectal cancer (mCRC) patients exhibiting poor prognosis under the conventional chemotherapy regimen. Recently, the chemotherapy-free combination of encorafenib and cetuximab has been approved as the standard of care for previously treated BRAF p.V600E mCRC patients, and genomic testing for BRAF mutations at the time of mCRC diagnosis is currently recommended. In clinical practice, BRAF mutation testing strategies are dramatically impacted by a lack of harmonization and standardization, both in the pre-analytical and analytical phases, which can result in BRAF-mutated patients not receiving the most appropriate therapy at recurrence. This paper proposes nine statements providing practical and concise advice on BRAF mutation testing in CRC, derived from collegial discussion and analysis of a multidisciplinary team of experts, including referral Italian oncologists and pathologists. The statements overview pivotal aspects implied in the detection, treatment and management of BRAF-mutated patients and have been drafted to represent a valuable tool for healthcare professionals committed to mCRC patient management. In addition, they represent a platform for implementing diagnostic-therapeutic workflows that can adapt to the variability of local resources while respecting the high-quality standards required by modern precision oncology.

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Due to a lack of clear symptoms, patients often present with advanced disease, with limited clinical intervention options. The high mortality rate of PDAC is, however, also a result of several other factors that include a high degree of heterogeneity and treatment resistant cellular phenotypes. Molecular subtypes of PDAC have been identified that are thought to represent these cellular phenotypes at the tissue level. The epigenetic landscape is an important factor that dictates these subtypes. Permissive epigenetic landscapes serve as drivers of molecular heterogeneity and cellular plasticity in developing crypts as well as metaplastic lesions. Drawing parallels with other cancers, we hypothesize that epigenetic permissiveness is a potential driver of cellular plasticity in PDAC. In this review will explore the epigenetic alterations that underlie PDAC cell states and relate them to cellular plasticity from other contexts. In doing so, we aim to highlight epigenomic drivers of PDAC heterogeneity and plasticity and, with that, offer some insight to guide pre-clinical research.

Novel therapies are driving meaningful changes to the management of endometrial cancer (EC). Herein, a systematic literature review was conducted to evaluate the efficacy and safety of first-line treatments for advanced/recurrent EC. Searches were conducted using multiple databases through October 26, 2023. In total, 108 records of 57 unique trials (48 of first-line therapies) met the inclusion criteria. Baseline characteristics varied by study, and sample sizes ranged from 28 to 1328. Median progression-free survival was reported in 28 trials (range, 1.9-18.8 months), median overall survival in 26 trials with mature data (range, 6.9-41 months), and safety in 21 trials evaluating first-line systemic therapy ± maintenance. The potentially high risk of adverse events may outweigh the suboptimal efficacy benefits reported for conventional chemotherapy or hormonal therapies. The safety and efficacy of immunotherapies identified within are expected to contribute to a paradigm shift in the management of primary advanced/recurrent EC.

Introduction: Cancer cachexia is a clinical condition characterized by recognizable "sickness behaviors" accompanied by loss of lean body tissue. The Global Leadership on Malnutrition (GLIM) has proposed phenotypic (unintentional weight loss, low body mass index and low muscle mass) and aetiologic (reduced food intake and inflammation or disease burden) diagnostic criteria. Recent work has suggested serum lactate dehydrogenase (LDH) might represent a 3^rd aetiologic criteria. Little is known of its relationship with GLIM. A systematic review and meta-analysis of their comparative prognostic value and association was performed.

Methods: A search of electronic databases (PubMed, Medline, Ovid, Cochrane) up to February 2023 was used to identify studies that compared the prognostic value of LDH and components of the GLIM criteria in cancer. An analysis of the relationship between LDH and the components of GLIM was undertaken where this data was available. RevMan 5.4.1 was used to perform a meta-analysis for each diagnostic criteria that had 3 or more studies which reported hazard ratios with a 95 per cent confidence interval for overall survival (OS).

Results: A total of 119 studies were reviewed. Advanced lung cancer was the most studied population. Included in the meta-analysis were 6 studies (n=2,165) on LDH and weight loss, 17 studies (n=7,540) on LDH and low BMI, 5 studies (n=758) on LDH and low muscle mass, 0 studies on LDH and food intake and 97 studies (n=37,185) on LDH and inflammation. There was a significant association between elevated serum LDH and each of low BMI (OR 1.39, 1.09 - 1.77; p=0.008), elevated NLR (OR 2.04, 1.57 - 2.65; p<0.00001) and elevated CRP (OR 2.58, 1.81 - 3.67; p<0.00001). There was no association between elevated serum LDH and low muscle mass. Only one study presented data on the association between LDH and unintentional weight loss. Elevated LDH showed a comparative OS (HR 1.86, 1.60 - 2.16; p<0.00001) to unintentional weight loss (HR 1.57, 1.23 - 1.99; p=0.0002) and had a similar OS (HR 2.01, 1.73 - 2.34; p<0.00001) to low BMI (HR 1.57, 1.29 -2.90; p<0.0001). LDH also showed an OS (HR 2.25, 1.76 - 2.87; p<0.00001) congruous with low muscle mass (HR 1.93, 1.14 - 3.27; p=0.01) and again, LDH conferred as poor an OS (HR 1.71, 1.60 - 1.82; p<0.00001) as elevated NLR (HR 1.57, 1.44 - 1.71; p<0.00001) or CRP (HR 1.53, 1.41 - 1.65; p<0.00001).

Conclusion: Current literature suggests elevated serum LDH is associated with inflammation in cancer (an aetiologic GLIM criterion), however more work is required to establish the relationship between LDH and the phenotypic components of GLIM. Additionally, elevated serum LDH appears to be a comparative prognosticator of overall survival in cancer when compared to the GLIM criteria.