Optimal Sequence for Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer: An Evidence-Based Review.

INTRODUCTION: Historically, multimodal therapeutic strategies involving preoperative chemoradiotherapy (CRT), surgery, and adjuvant chemotherapy (CT) have been employed to treat locally advanced rectal cancer (LARC). Total Neoadjuvant Therapy (TNT) is showing promise in improving outcomes. Despite its benefits, the optimal sequencing within TNT-whether induction chemotherapy should precede or follow chemoradiotherapy-remains a critical question. This study endeavors to explore the effects of different TNT sequencing strategies on patient outcomes, including tumor downstaging, pathological response, organ preservation, and the balance between efficacy and tolerability. METHODS: Our methodology entailed a comprehensive literature review conducted on Medline, focusing on recent research, including retrospective studies, systematic reviews, and clinical trials. The review emphasized the comparison of induction chemotherapy versus consolidation chemotherapy within TNT regimens, assessing outcomes such as pathological response, organ preservation rates, and adverse effects. To ensure the selection of appropriate and high-quality studies, specific inclusion and exclusion criteria were applied. RESULTS: The analysis revealed that induction chemotherapy might lead to decreased adherence to subsequent chemoradiotherapy while offering an early intervention against micrometastasis and potentially improving overall chemotherapy compliance. Conversely, consolidation chemotherapy has been associated with higher pathological complete response (pCR) rates and improved tolerability, indicating its potential for patients requiring local symptom relief or those eligible for a nonoperative management approach. Comparative studies like CAO/ARO/AIO-12 and the OPRA trials have significantly contributed to our understanding, suggesting that while both strategies have distinct advantages, the choice between induction and consolidation chemotherapy should be tailored based on individual patient profiles and tumor characteristics. CONCLUSION: This narrative review underscores the importance of a nuanced approach to TNT sequencing in locally advanced rectal cancer, highlighting the need for further research to refine treatment strategies.

Potential role of transmembrane 9 superfamily member 1 as a biomarker in urothelial cancer.

Bladder cancer is a urological tumor with high rates of recurrence despite recent advances in novel therapies. Many proteins involved in the molecular mechanisms are currently an enigma, especially the transmembrane 9 superfamily member 1 which has an unclear function. Wei et al published the function and mechanism of this protein, and showed that it could participate in the proliferation, migration and invasion of tumor cells in bladder cancer, therefore treatments directed against this protein may be beneficial in avoiding this condition.

Circulating tumor cells in pancreatic cancer: The prognostic impact in surgical patients.

Pancreatic cancer is associated with a poor prognosis, even in the early stages, mainly due to metastatic progression. New diagnostic techniques that predict unfavorable outcomes are needed in order to improve treatment strategies. Circulating tumor cells (CTCs) are showing promising results as a predictive biomarker for various tumors. In this editorial we comment on the article by Zhang et al, who published the first systematic review and meta-analysis evaluating the prognostic value of CTCs as biomarkers in early-stage pancreatic cancer patients undergoing surgery. CTCs were detected in peripheral or central venous system blood, before or during surgery. Positive CTCs showed a correlation with decreased overall survival and decreased relapse-free, disease-free and progression-free survival in this meta-analysis. However, the heterogeneity was significant. The authors suggest that this result was related to the separation methods used between studies, but other differences such as the margin status or the neoadjuvant and adjuvant treatments used are also important to consider. CTCs may be a potential prognostic biomarker in pancreatic cancer patients, but it is necessary to compare and standardize the platforms used to isolate CTCs, to compare different biomarkers from liquid biopsy and to determine the impact on prognosis when therapeutic changes are made based on CTCs levels.

Current challenges in the treatment of gliomas: The molecular era.

Gliomas originate from glial cells in the central nervous system. Approximately 80%-85% of malignant brain tumors in adults are gliomas. The most common central nervous system tumor in children is low-grade pediatric glioma. Diagnosis was determined by histological features until 2016 when the World Health Organization classification integrated molecular data with anatomopathological information to achieve a more integral diagnosis. Molecular characterization has led to better diagnostic and prognostic staging, which in turn has increased the precision of treatment. Current efforts are focused on more effective therapies to prolong survival and improve the quality of life of adult and pediatric patients with glioma. However, improvements in survival have been modest. Currently, clinical guidelines, as well as the article by Mohamed et al accompanying this editorial piece, are adapting treatment recommendations (surgery, chemotherapy, and radiotherapy) according to diagnosis and prognosis guided by molecular biomarkers. Furthermore, this paves the way for the design of clinical trials with new therapies, which is especially important in pediatric gliomas.

Is There an Opportunity to De-Escalate Treatments in Selected Patients with Metastatic Hormone-Sensitive Prostate Cancer?

The treatment landscape for metastatic hormone-sensitive prostate cancer continues to evolve, with systemic treatment being the mainstay of current treatment. Prognostic and predictive factors such as tumour volume and disease presentation have been studied to assess responses to different treatments. Intensification and de-escalation strategies arouse great interest, so several trials are being developed to further personalize the therapy in these populations. Is there an optimal sequence and a possible option to de-intensify treatment in selected patients with a favourable profile? This and other goals will be the subject of this review.

A randomised trial of short- vs long-term androgen deprivation with salvage radiotherapy for biochemical failure following radical prostatectomy: URONCOR 06-24.

BACKGROUND: Salvage radiotherapy (SRT) and androgen-deprivation therapy (ADT) are widely used in routine clinical practice to treat patients with prostate cancer who develop biochemical recurrence (BCR) after radical prostatectomy (RP). However, there is no standard-of-care consensus on optimal duration ADT. Investigators propose three distinct risk groups in patients with prostate cancer treated with SRT in order to better define the indications and duration of ADT combined with SRT. STUDY DESIGN: The URONCOR 06-24 trial (ClinicalTrials.gov identifier NCT05781217) is a prospective, multicentre, randomised, open-label, phase III, clinical trial. The aim of the trial is to determine the impact of short-term (6 months) vs long-term (24 months) ADT in combination with SRT on distant metastasis-free survival (MFS) in patients with prostate cancer with BCR after RP (intermediate and high risk). ENDPOINTS: The primary endpoint is 5-year MFS rates in patients with prostate cancer treated with long- vs short-term ADT in combination with SRT. Secondary objectives are biochemical-relapse free interval, pelvic progression-free survival, time to start of systemic treatment, time to castration resistance, cancer-specific survival, overall survival, acute and late toxicity, and quality of life. METHODS AND ANALYSIS: Total of 534 patients will be randomised 1:1 to ADT 6 months or ADT 24 months with a luteinizing hormone-releasing hormone analogue in combination with SRT, stratified by risk group and pathological lymph node status. ETHICS AND DISSEMINATION: The study is conducted under the guiding principles of the World Medical Association Declaration of Helsinki. The results will be disseminated at research conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: EudraCT number 2021-006975-41.

Analyzing diagnostic and treatment wait times for lung cancer Patients: Key insights from a provincial registry study.

BACKGROUND: Lung cancer (LC) remains the leading cause of cancer-related mortality globally, necessitating timely diagnosis and treatment to improve patient outcomes. This study aimed to evaluate the timeliness of care for LC patients at a public hospital in Almería, Spain, assess adherence to guidelines, and explore associations between timeliness and survival. METHODS: A retrospective cohort study was conducted, reviewing medical records of LC patients diagnosed between 2019 and 2021. Quality indicators, adapted from prevailing guidelines, facilitated the assessment of care timeliness, with a focus on diagnostic and treatment wait times. Cox regression modeling was employed to explore survival associations, adjusting for covariates including age, performance status, stage, histology, and treatment modalities. RESULTS: Of 539 patients included, most (79.84 %) had initial specialist contact within 7 days, and 82.25 % received diagnosis within 30 days. However, delays were observed in treatment initiation, with surgery experiencing the longest median wait time (78 days). Survival analysis showed no significant difference between shorter and longer diagnostic (HR: 0.87, 95 % CI: 0.62-1.24) or treatment intervals (HR: 1.14, 95 % CI: 0.83-1.58). Multivariate analysis identified age, performance status, stage, histology, and treatment as prognostic factors. CONCLUSION: This study highlights the importance of timely diagnosis and treatment in improving lung cancer outcomes. Despite achieving diagnostic targets, treatment delays were common, particularly for surgical interventions. These findings underscore the need for enhanced coordination and efficient care pathways to minimize delays, ultimately improving survival rates and quality of life for lung cancer patients. Addressing these issues is crucial for optimizing lung cancer care delivery in the future.

Vitamin D and prostate cancer prevention.

Vitamin D is a hot topic nowadays, especially its relationship with cancer prevention. Normally, vitamin D is associated with bone health principally, but the new research has discovered an impact on immune function and cellular signaling, even in same studies talk about a hormone, however, the most important relationship is its implication in cellular processes, inhibiting cancer growth. For now, the recent studies are oriented about a benefit and a cause-effect relationship between prostate cancer and normal levels of vitamin D. This premise opens a lot of questions in this scenario. This editorial highlighted the most important studies in this area.

Current status of anaplastic thyroid carcinoma.

In this editorial we comment on the article by Pavlidis et al, published in the recent issue of the World Journal of Oncology. We focus on the recent contributions in the management of anaplastic thyroid carcinoma, highlighting the importance of surgery and radiotherapy as first line therapies in its management and the introduction of new systemic therapies beyond chemotherapy, focused on molecular alterations, an essential step in the diagnosis and included in clinical guidelines for the selection of the ideal treatment. In contrast to other neoplasms, immunotherapy, is still beginning in studies of this pathology with encouraging results. Therefore, multimodal management of the pathology together with new drugs seems to be the logical step to increase the survival of this neoplasm.

Hyoid metastasis an unusual location from lung cancer.

Bone metastases from lung cancer account for 8.5%, with those located in the hyoid bone being extremely rare. In this editorial, we made a review about Hsu et al case report highlighted the importance of palliative radiotherapy, even with an unusual but effective scheme in pain control in a patient with non-small cell lung cancer in stage IV.

Neoadjuvant treatment of rectal cancer: Where we are and where we are going.

Locally advanced rectal cancer requires a multidisciplinary approach based on total neoadjuvant treatment with radiotherapy (RT) and chemotherapy (ChT), followed by deferred surgery. Currently, alternatives to the standard total neoadjuvant therapy (TNT) are being explored, such as new ChT regimens or the introduction of immunotherapy. With standard TNT, up to a third of patients may achieve a complete pathological response (CPR), potentially avoiding surgery. However, as of now, we lack predictive markers of response that would allow us to define criteria for a conservative organ strategy. The presence of mutations, genes, or new imaging tests is helping to define these criteria. An example of this is the diffusion coefficient in the diffusion-weighted sequence of magnetic resonance imaging and the integration of this imaging technique into RT treatment. This allows for the monitoring of the evolution of this coefficient over successive RT sessions, helping to determine which patients will achieve CPR or those who may require intensification of neoadjuvant therapy.

Pembrolizumab autoimmune related diabetes: Moving forward, keep learning.

Immune checkpoint inhibitors (and more specifically programmed cell death 1/programmed cell death ligand 1 inhibitors as Pembrolizumab) initiated a revolution in the field of melanoma and have now expanded to several tumor subtypes and in increasingly broader clinical contexts, including the adjuvant and neoadjuvant setting, with potentially curable patients and prolonged survival. The side effects related to these drugs include a wide spectrum of manifestations, with endocrinological adverse events being some of the most frequent. Pembrolizumab-induced type 1 diabetes mellitus is an infrequent but potentially serious and not clearly reversible side effect that possesses characteristic clinical features and has high morbidity and mortality, with a chronic impact on quality of life. The etiopathogenesis of this phenomenom needs to be further investigated and a collaborative effort through the involvement of oncologists and other medical specialists is necessary for the correct identification and management of patients at risk.

Liquid biopsy to personalize treatment for metastatic prostate cancer.

Liquid biopsy is an innovative approach that provides a more complete understanding of treatment response and prognosis in monitoring metastatic prostate cancer. It complements invasive tissue biopsy and involves the assessment of various biomarkers in body fluids such as blood, semen, and urine. Liquid biopsy analyzes circulating tumor cells, extracellular vesicles, circulating tumor DNA, and the secretome. This is particularly important given the heterogeneity of prostate cancer and the need for better prognostic biomarkers. Liquid biopsy can personalize the treatment of homonosensitive and castration-resistant metastatic prostate cancer by acting as a predictive and prognostic tool. This review discusses various biomarkers, assay techniques, and potential applications in daily clinical practice, highlighting the exciting possibilities that this emerging field holds for improving patient outcomes.

Feasibility and Acute Toxicity of Hypo-Fractionated Radiotherapy on 0.35T MR-LINAC: The First Prospective Study in Spain.

This observational, descriptive, longitudinal, and prospective basket-type study (Registry #5289) prospectively evaluated the feasibility and acute toxicity of hypo-fractionated radiotherapy on the first 0.35T MR-LINAC in Spain. A total of 37 patients were included between August and December 2023, primarily with prostate tumors (59.46%), followed by pancreatic tumors (32.44%). Treatment regimens typically involved extreme hypo-fractionated radiotherapy, with precise dose delivery verified through quality assurance measures. Acute toxicity assessment at treatment completion revealed manageable cystitis, with one case persisting at the three-month follow-up. Gastrointestinal toxicity was minimal. For pancreatic tumors, daily adaptation of organ-at-risk (OAR) and gross tumor volume (GTV) was practiced, with median doses to OAR within acceptable limits. Three patients experienced gastrointestinal toxicity, mainly nausea. Overall, the study demonstrates the feasibility and safety of extreme hypo-fractionated radiotherapy on a 0.35T MR-LINAC, especially for challenging anatomical sites like prostate and pancreatic tumors. These findings support the feasibility of MR-LINAC-based radiotherapy in delivering precise treatments with minimal toxicity, highlighting its potential for optimizing cancer treatment strategies.

Management of lateral pelvic lymph nodes in rectal cancer: Is it time to reach an Agreement?

In this editorial, we proceed to comment on the article by Chua et al, addressing the management of metastatic lateral pelvic lymph nodes (mLLN) in stage II/III rectal cancer patients below the peritoneal reflection. The treatment of this nodal area sparks significant controversy due to the strategic differences followed by Eastern and Western physicians, albeit with a higher degree of convergence in recent years. The dissection of lateral pelvic lymph nodes without neoadjuvant therapy is a standard practice in Eastern countries. In contrast, in the West, preference leans towards opting for neoadjuvant therapy with chemoradiotherapy or radiotherapy, that would cover the treatment of this area without the need to add the dissection of these nodes to the total mesorectal excision. In the presence of high-risk nodal characteristics for mLLN related to radiological imaging and lack of response to neoadjuvant therapy, the risk of lateral local recurrence increases, suggesting the appropriate selection of strategies to reduce the risk of recurrence in each patient profile. Despite the heterogeneous and retrospective nature of studies addressing this area, an international consensus is necessary to approach this clinical scenario uniformly.

Bridging the gap: Predicting brain metastasis in breast cancer.

Chen et al explored clinicopathological features and prognostic factors, revealing advanced tumor stage, lung metastases, HER-2 overexpression, and triple-negative status as key contributors. Recent research connects astrocytes' role in brain metastasis with signaling pathways and the impact of Trastuzumab on HER-2 tumor survival. Factors such as positive HER2 status, lack of estrogen receptor expression, and liver metastasis are identified as additional risk factors. The routine use of magnetic resonance imaging, insights into gene mutations associated with metastasis, and the role of radiotherapy, including prophylaxis possibilities, is controversial in clinical practice. Understanding these risk factors in a multidisciplinary collaboration is precise for local treatments and targeted therapies, particularly for HER2+ tumors, impacting directly on longer survival.

MR-LINAC, a New Partner in Radiation Oncology: Current Landscape.

Technological advances in radiation oncology are oriented towards improving treatment precision and tumor control. Among these advances, magnetic-resonance-image-guided radiation therapy (MRgRT) stands out, with technological advances to deliver targeted treatments adapted to a tumor's anatomy on the day while minimizing incidental exposure to organs at risk, offering an unprecedented therapeutic advantage compared to X-ray-based IGRT delivery systems. This new technology changes the traditional workflow in radiation oncology and requires an evolution in team coordination to administer more precise treatments. Once implemented, it paves the way for newer indication for radiation therapy to safely deliver higher doses than ever before, with better preservation of healthy tissues to optimize patient outcomes. In this narrative review, we assess the technical aspects of the novel linear accelerators that can deliver MRgRT and summarize the available published experience to date, focusing on oncological results and future challenges.