Cancer treatment reviews最新文献

The incidence of breast cancer in ≤ 40 yr-old women (YWBC) has been steadily increasing in recent decades. Although this group of patients represents less than 10 % of all newly diagnosed BC cases it encompasses a significant burden of disease. Usually underrepresented in clinical trials, YWBCs are also characterized by late diagnoses and poorly differentiated, aggressive-subtype disease, partly explaining its poor prognosis along with a high recurrence risk, and high mortality rates. On the other hand, YWBC treatment poses unique challenges such as preservation of fertility, and long-term toxicity and adverse events. Herein, we summarize the current evidence in hormone receptor-positive YWBC including specific risk factors, clinicopathologic and genomic features, and available evidence on response to chemotherapy and endocrine therapy. Overall, we advocate for a more comprehensive multidisciplinary healthcare model to improve the outcomes and the quality of life of this subset of younger patients.

This review presents a comprehensive comparative analysis of international guidelines for managing advanced, non-functioning, well-differentiated pancreatic neuroendocrine tumors (panNETs). PanNETs, which represent a significant proportion of pancreatic neuroendocrine neoplasms, exhibit diverse clinical behaviors and prognoses based on differentiation, grading, and other molecular markers. The varying therapeutic strategies proposed by different guidelines reflect their distinct emphases and regional considerations, such as the ESMO guideline’s focus on advanced disease management and the ENETS guidance paper’s multidisciplinary approach. This review examines the most recent guidelines from ESMO, NCCN, ASCO, ENETS, and NANETS, analyzing the recommendations for first-line therapies and subsequent treatment pathways in different clinical scenarios. Significant variations are observed in the recommendations, particularly concerning the choice and sequence of systemic therapies, the role of tumor grading and the Ki-67 index in therapeutic decisions, and the integration of regional regulatory and clinical practices. The analysis highlights the need for a tailored approach to managing advanced NF panNETs, advocating for flexibility in applying guidelines to account for individual patient circumstances and the evolving evidence base. This work underscores the complexities of managing this patient population and the critical role of a multidisciplinary team in optimizing treatment outcomes.

Immune checkpoint inhibition has transformed the treatment landscape of advanced melanoma and long-term survival of patients is now possible. However, at least half of the patients do not benefit sufficiently. Metabolic reprogramming is a hallmark of cancer cells and may contribute to both tumour growth and immune evasion by the tumour. Preclinical studies have indeed demonstrated that modulating tumour metabolism can reduce tumour growth while improving the functionality of immune cells. Since metabolic pathways are commonly shared between immune and tumour cells, it is essential to understand how modulating tumour metabolism in patients influences the intricate balance of pro-and anti-tumour immune effects in the tumour microenvironment. The key question is whether modulating tumour metabolism can inhibit tumour cell growth as well as facilitate an anti-tumour immune response. Here, we review current knowledge on the effect of tumour metabolism on the immune response in melanoma. We summarise metabolic pathways in melanoma and non-cancerous cells in the tumour microenvironment and discuss models and techniques available to study the metabolic-immune interaction. Finally, we discuss clinical use of these techniques to improve our understanding of how metabolic interventions can tip the balance towards a favourable, immune permissive microenvironment in melanoma patients.

Objective

In squamous cell carcinoma of the penis (PeCa), treatment options for primary tumors vary by disease stage and may include surgery, radiation, topical chemotherapy, or laser excision. This review aims to highlight the current evidence on the value of radiotherapy as an organ-preserving strategy in primary PeCa.

Material and Methods

Manuscripts on primary PeCa treatment with external beam radiotherapy (EBRT) and brachytherapy were evaluated via Scopus, PubMed/MEDLINE, and Web of Science^TM (2013–2023) to assess their efficacy and safety. Animal studies, studies with <5 patients, and case reports were excluded.

Results

Radiotherapy offers the potential for organ preservation with tumor control rates comparable to radical surgery, while disease-specific survival rates up to 70 % were experienced with EBRT. Brachytherapy (BT) is the preferred method of irradiation for glans-limited tumors, whereas a higher relapse risk is expected for tumors >4 cm. BT shows 73 % amputation-free survival at 8–10 years and 81 % progression-free survival at 5–10 years. Compared with BT, total amputation significantly improves 5-year disease-free survival rate. BT offers a superior 5-year local control and penile preservation rates compared to EBRT. Common acute toxicities of brachytherapy include radiodermatitis, sterile urethritis, and urethral adhesions. The primary late adverse events of BT are soft tissue necrosis (0–31 %) and meatal stenosis (0–43 %).

Conclusion

BT is a favorable radiation modality, offering an efficient and conservative approach. HDR BT is favored for its enhanced dose distribution and radiation protection. Collaboration between radiation oncologists and urologists is essential in order to provide an optimal patient selection and manage toxicities thus optimizing patient outcomes.

Over half of patients with cancer receive radiation therapy during the course of their disease. Decades of radiobiological research have identified 6 parameters affecting the biological response to radiation referred to as the 6 “Rs”: Repair, Radiosensitivity, Repopulation, Redistribution, Reoxygenation, and Reactivation of the anti-tumour immune response. Extracellular Vesicles (EVs) are small membrane-bound particles whose multiple biological functions are increasingly documented. Here we discuss the evidence for a role of EVs in the orchestration of the response of cancer cells to radiotherapy. We highlight that EVs are involved in DNA repair mechanisms, modulation of cellular sensitivity to radiation, and facilitation of tumour repopulation. Moreover, EVs influence tumour reoxygenation dynamics, and play a pivotal role in fostering radioresistance. Last, we examine how EV-related strategies could be translated into novel strategies aimed at enhancing the efficacy of radiation therapy against cancer.

Concurrent chemoradiotherapy (cCRT) followed by one year of consolidation durvalumab is the current standard-of-care for patients with unresectable stage III non-small cell lung cancer (NSCLC), of good functional status. However, cCRT and consolidation durvalumab may be challenging to administer for selected patient populations underrepresented or even excluded in clinical trials: older and/or frail patients; those with cardiovascular or respiratory comorbidities in which treatment-related adverse events may be higher, and patients with pre-existing autoimmune disorders for whom immunotherapy use is controversial. In this narrative review, we discuss the current evidence, challenges, ongoing clinical trials and potential future treatment scenarios in relevant subgroups of patients with locally advanced NSCLC, who are underrepresented in clinical trials.

Small-cell lung cancer (SCLC), accounting for 10–20 % of all lung tumors, represents the most aggressive high-grade neuroendocrine carcinoma. Most patients are diagnosed with extensive-stage SCLC (ES-SCLC), with brian metastases identified in ∼ 80 % of cases during the disease cours, and the prognosis is dismal, with a 5-year survival rate of less than 5 %.

Current available treatments in the second-line setting are limited, and topotecan has long been the only FDA-approved drug in relapsed or refractory ES-SCLC, until the recent approval of lurbinectedin, a selective inhibitor of RNA polymerase II.

Temozolomide (TMZ) is an oral alkylating agent, which showed single-agent activity in SCLC, particularly among patients with O⁶-methylguanine-DNA methyltransferase (MGMT) promoter methylation.

Several studies have revealed the synergistic activity of temozolomide with poly-ADP-ribose polymerase (PARP) inhibitors, that prevent repair of TMZ-induced DNA damage.

This review focuses on the rationale for the use of TMZ in ES-SCLC and provides an overview of the main trials that have evaluated and are currently investigating its role, both as a single-agent and in combinations, in relapse or refractory disease.

Overall survival benefit of total neoadjuvant treatment (TNT) remains unconfirmed. Thus, in our opinion, the main rationale for using TNT is a planned watch-and-wait (w&w) strategy to improve patients’ long-term quality of life through organ preservation. The OPRA randomized trial, which examined a planned w&w strategy using TNT, showed a higher organ preservation rate but also a higher regrowth rate compared to studies on the opportunistic w&w strategy. Higher rates of complete clinical response with TNT did not improve disease-free survival compared to historical controls. Therefore, the gain in organ-sparing capability might not be balanced by the increased oncological risk. The ultimate local failure rate in the intention-to-treat analysis of the OPRA trial was 13% for induction chemotherapy and 16% for consolidation chemotherapy, which seems higher than expected compared to 8% in a meta-analysis of w&w studies or 12% after TNT and surgery in the PRODIGE-23 and RAPIDO trials, which enrolled patients with more advanced cancers than the OPRA trial. Other studies also suggest worse local control when surgery is delayed for radio–chemoresistant cancers. Our review questions the safety of the planned w&w strategy using TNT in unselected patients. To reduce the oncological risk while maintaining high organ preservation rates, we suggest that the planned w&w strategy using TNT requires a two-tier patient selection process: before treatment and after tumor response assessment at the midpoint of consolidation chemotherapy. These robust selections should identify patients who are unlikely to achieve organ preservation with TNT and would be better managed by preoperative chemoradiotherapy (without consolidation chemotherapy) and surgery, or by discontinuing consolidation chemotherapy and proceeding directly to surgery.

Background

Proton pump inhibitors (PPIs) are widely used in cancer patients despite accumulating data showing that they can impact the efficacy of major anticancer drugs. This is particularly important with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (CPIs).

Results

Most TKIs require gastric acidity for their absorption and some retrospective series demonstrated that coprescription decreases the survival benefit of some TKI use (erlotinib, gefitinib and pazopanib). Relations between microbiota, the immune system, and the efficacy of immunotherapy are now obvious, just as modifications to gut flora after PPIs use are well-known. Many retrospective articles, including articles based on individual-participant data from randomized studies, demonstrated that patients treated with CPIs have a poorer outcome (overall survival, progression-free survival and response rate) when they received PPIs concomitantly, while there was no impact of such coprescription among patients in control arms, not treated with immunotherapies. Similar data were also observed in patients treated with palbociclib.

Conclusion

For these interactions, it is very important to use the precautionary principle and warn patients and physicians about this. In patients who require acid suppression because of severe symptoms, using antacids or H2 blockers could be recommended.

Melanoma metabolism can be reprogrammed by activating BRAF mutations. These mutations are present in up to 50% of cutaneous melanomas, with the most common being V600E. BRAF mutations augment glycolysis to promote macromolecular synthesis and proliferation. Prior to the development of targeted anti-BRAF therapies, these mutations were associated with accelerated clinical disease in the metastatic setting. Combination BRAF and MEK inhibition is a first line treatment option for locally advanced or metastatic melanoma harboring targetable BRAF mutations. This therapy shows excellent response rates but these responses are not durable, with almost all patients developing resistance. When BRAF mutated melanoma cells are inhibited with targeted therapies the metabolism of those cells also changes. These cells rely less on glycolysis for energy production, and instead shift to a mitochondrial phenotype with upregulated TCA cycle activity and oxidative phosphorylation. An increased dependence on glutamine utilization is exhibited to support TCA cycle substrates in this metabolic rewiring of BRAF mutated melanoma. Herein we describe the relevant core metabolic pathways modulated by BRAF inhibition. These adaptive pathways represent vulnerabilities that could be targeted to overcome resistance to BRAF inhibitors. This review evaluates current and future therapeutic strategies that target metabolic reprogramming in melanoma cells, particularly in response to BRAF inhibition.