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.

Docetaxel Provides Oncological Benefits in the Era of New-Generation Androgen Receptor Inhibitors - or Is Three a Crowd?

In recent years, several systemic therapies have been introduced for metastatic hormone-sensitive prostate cancer, including androgen deprivation therapy (ADT) combined with docetaxel (Doc) and/or new-generation androgen receptor signaling inhibitors (ARSI). Trials evaluating ADT + ARSI have consistently demonstrated an overall survival (OS) benefit for doublet therapy over ADT alone. Similarly, the STOPCaP meta-analysis showed an OS benefit in favor of ADT + Doc versus ADT alone. ARSI, Doc, and ADT have different antitumor mechanisms, thus potentiating the effect of combination therapy. Two randomized trials showed that the addition of ARSI to ADT + Doc improves OS, especially for synchronous high-volume disease. However, the real question about triplet therapy remains unanswered: whether combining Doc with ARSI improves outcomes compared to ADT + ARSI. As there are no head-to-head comparisons, this narrative review aims to summarize the current evidence regarding triplet therapy versus doublet therapy including ADT+ ARSI.

Prostate Cancer: Management of Biochemical Recurrence after Surgery

Radical prostatectomy (RP) is one of the primary treatment options for localised prostate cancer (PCa). Despite its curativeintent, 1/3 of patients will experience biochemical recurrence (BCR) during follow-up. Experts have devoted efforts to associatethe influence of each individual factor with the risk of BCR to select the optimal treatment for each patient. Optimal managementmust aim to find a balance between delaying the onset of metastatic disease and overtreating an indolent disease with treatmentsthat can affect quality of life of the patients. Thus far, effective treatment options for men with BCR remain controversial interms of ideal treatment timing (adjuvant vs. salvage), radiotherapy (RT) fields and doses, selection and duration of systemictherapy and potential synergies between treatments and their therapeutic sequencing. Next-generation imaging techniques, suchas Prostate-Specific Membrane Antigen Positron Emission Tomography, are used for early detection of disease progression andexact site of recurrence or progression, thereby enhancing decision making for future disease management. In this review, weevaluate available evidence of controversial topics regarding BCR after RP and explore future directions, such as prognosticand/or predictive factors of response, genetic panels, second-generation hormone treatments, ultra-hypofractionated RT andongoing clinical trials in this clinical scenario. (AU)

Coronavirus disease 2019 and lung cancer: where are we?

Oncology patients are more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection due to hospital contact and an immunological system that can be compromised by antineoplastic therapy and supportive treatments. Certain similarities have been described in the physiopathology of coronavirus disease 2019 (COVID-19) and lung cancer (LC) that may explain the higher probability of these patients of developing a more serious disease with more frequent hospitalizations and even death, especially with the addition of smoking, cardiovascular and respiratory comorbidities, old age and corticosteroids use. Pre-existing lesions and cancer therapies change the normal architecture of the lungs, so diagnostic scales such as COVID-19 Reporting and Data System (CO-RADS) are of vital importance for a correct diagnosis and patient homogenization, with a high inter-observer correlation. Moreover, anticancer treatments have required an adaptation to reduce the number of visits to the hospital [hypofractionated radiotherapy (RT), larger intervals between chemotherapy cycles, delay in follow-up tests, among others]. In a way, this has also caused a delay in the diagnosis of new cancers. On the other hand, vaccination has had a positive impact on the mortality of these patients, who maintain a similar seroprevalence to the rest of the population, with a similar impact in mortality.

Jorge clinical study: 10-year outcomes of risk-adapted radiotherapy defined by multiparametric MRI for prostate cancer.

PURPOSE: To analyze the 10-year biochemical relapse-free survival (BRFS), locoregional relapse-free survival (LRFS), metastasis-free survival (MFS), and overall survival (OS) in patients diagnosed with localized prostate adenocarcinoma treated with radiotherapy (RT) ± androgen deprivation therapy (ADT), according to the risk groups based on multiparametric magnetic resonance imaging (mpMRI) instead of digital rectal exam (DRE). METHODS: We retrospectively evaluated 140 consecutive patients diagnosed with localized prostate adenocarcinoma, stratified into different risk groups-low (LR), intermediate (IR), and high (HR) by mpMRI results. RESULTS: After a median follow-up of 104 months, in LR group (n = 15), 10-year BRFS was 86.7%, 10-year LRFS was 86.7%, 10-year MFS was 93.3%, and 10-year OS was 100%. In IR group (n = 80), 10-year BRFS was 80.5%, 10-year LRFS was 86.1%, 10-year MFS was 92.6%, and 10-year OS was 76%. In HR group (n = 45), 10-year BRFS was 72.8%, 10-year LRFS was 78.7%, 10-year MFS was 82.1%, and 10-year OS was 77% (2 deaths from prostate cancer). According to mpMRI results, 36 (25.7%) patients change the risk group and 125 (89.28%) patients change the TNM stage. There was a trend for higher metastatic relapse in patients who switched from IR to HR (due to mpMRI) versus the patients who remained in the IR (20%, vs. 1.81% p = 0.059). Multivariate analysis showed that locoregional relapse was strongly associated with distant relapse (OR = 9.28; 95%CI: 2.60-33.31). There were no cases of acute grade 3 toxicity. Late grade 3 genitourinary, gastrointestinal, and sexual toxicity were 2.8%, 0.7%, and 1.2%, respectively. CONCLUSION: This is the first study with a 10-year median follow-up of patients diagnosed with localized prostate cancer treated with radiotherapy according to the risk groups established by mpMRI. Our findings show that mpMRI is a key tool to diagnose and establish risk groups in these patients, to optimize their treatment.

Total neoadjuvant therapy approach for the treatment of locally advanced rectal cancer. Where do we stand?

BACKGROUND: for the management of locally advanced rectal cancer (LARC), initial treatment with neoadjuvant chemoradiotherapy followed by surgery and chemotherapy in selected patients is considered one of the recommended options by the main international clinical guidelines. Nonetheless, the administration of all chemotherapy before definitive treatment (total neoadjuvant therapy or TNT) is an optimal alternative with a growing level of evidence that must be evaluated in multidisciplinary boards. This review summarizes the available data and controversies in this scenario. SUMMARY: we have analyzed the characteristics of the main published studies that assess the use of TNT in patients with LARC, evaluating their inclusion criteria and distinguishing between the employed radiotherapy fractionations, systemic agents, timing, and the implications of these treatments in regard to surgery and long-term oncological results. Our aim is to describe the evidence that supports the use of a specific regime in everyday clinical practice. KEY POINTS: there is solid evidence for the use of TNT in patients with LARC. There is no data indicating the superiority of one specific TNT scheme among all the existing options. International clinical guidelines leave the door open to choose the most adequate treatment based on the clinical and pathological characteristics of each patient. This review shows the different approaches to TNT and assesses the best options based on clinical evidence.

PEACE V-Salvage Treatment of OligoRecurrent nodal prostate cancer Metastases (STORM): Acute Toxicity of a Randomized Phase 2 Trial.

BACKGROUND: Treatment recommendations for patients with limited nodal recurrences are lacking, and different locoregional treatment approaches are currently being used. OBJECTIVE: The aim of this trial is to compare metastasis-directed therapy (MDT) with or without elective nodal pelvic radiotherapy (ENRT). DESIGN, SETTING, AND PARTICIPANTS: PEACE V-Salvage Treatment of OligoRecurrent nodal prostate cancer Metastases (STORM) is an international, phase 2, open-label, randomized, superiority trial (ClinicalTrials.gov identifier: NCT03569241). Patients diagnosed with positron emission tomography-detected pelvic nodal oligorecurrence (five or fewer nodes) following radical local treatment for prostate cancer were randomized in a 1:1 ratio between arm A (MDT and 6 mo of androgen deprivation therapy [ADT]) and arm B (ENRT [25 × 1.8 Gy] with MDT and 6 mo of ADT). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We report the secondary endpoint acute toxicity, defined as worst grade ≥2 Common Terminology Criteria for Adverse Events v4.0 gastrointestinal (GI) or genitourinary (GU) toxicity within 3 mo of treatment. The chi-square test was used to compare toxicity between treatment arms. We also compare the quality of life (QoL) using the European Organisation for Research and Treatment of Cancer QLQ C30 and PR25 questionnaires. RESULTS AND LIMITATIONS: Between June 2018 and April 2021, 196 patients were assigned randomly to MDT or ENRT. Ninety-seven of 99 patients allocated to MDT and 93 of 97 allocated to ENRT received per-protocol treatment. Worst acute GI toxicity proportions were as follows: grade ≥2 events in three (3%) in the MDT group versus four (4%) in the ENRT group (p = 0.11). Worst acute GU toxicity proportions were as follows: grade ≥2 events in eight (8%) in the MDT group versus 12 (13%) in the ENRT group (p = 0.95). We observed no significant difference between the study groups in the proportion of patients with a clinically significant QoL reduction from baseline for any subdomain score area. CONCLUSIONS: No clinically meaningful differences were observed in worst grade ≥2 acute GI or GU toxicity or in QoL subdomains between MDT and ENRT. PATIENT SUMMARY: We found no evidence of differential acute bowel or urinary side effects using metastasis-directed therapy and elective nodal radiotherapy for the treatment of patients with a pelvic lymph node recurrence.

Stereotactic body radiation therapy after radical prostatectomy: current status and future directions.

PURPOSE: Around 40% of men with intermediate-risk or high-risk prostate cancer will experience a biochemical recurrence after radical prostatectomy (RP). The aim of this review is to describe both toxicity and oncological outcomes following stereotactic body radiation therapy (SBRT) delivered to the prostate bed (PB). METHOD: In april 2023, we performed a systematic review of studies published in MEDLINE or ClinicalTrials.gov according to Preferred Reporting Items for Systematic Reviews, using the keywords "stereotactic radiotherapy" AND "postoperative" AND "prostate cancer". RESULTS: A total of 14 studies assessing either adjuvant or salvage SBRT to the whole PB or macroscopic local recurrence (MLR) within the PB, and SBRT on radiorecurrent MLR within the PB were included. Doses delivered to either whole PB or MLR between 30 to 40 Gy are associated with a low rate of late grade ≥ 2 genitourinary (GU) toxicity, ranging from 2.2 to 15.1%. Doses above 40 Gy are associated with increased rate of late GU toxicity, raising up to 38%. Oncological outcomes should be interpreted with caution, due to both short follow-up, heterogeneous populations and androgen deprivation therapy (ADT) use. CONCLUSION: PB or MLR SBRT delivered at doses up to 40 Gy appears safe with relatively low late severe GU toxicity rates. Caution is needed with dose-escalated RT schedules above 40 Gy. Further prospective trials are eagerly awaited in this disease setting.

Total neoadjuvant therapy for locally advanced rectal cancer: a narrative review.

Locally advanced rectal cancer has traditionally been treated with chemoradiotherapy (CRT) followed by surgery and adjuvant chemotherapy. However, a new strategy, total neoadjuvant therapy, involves the administration of CRT and neoadjuvant chemotherapy with the aim of eradicating micrometastases earlier and achieving greater control of the disease. The use of total neoadjuvant therapy has shown higher rates of pathological complete response and resectability compared with CRT, including improved survival. Nevertheless, distant relapse is the main cause of morbidity and mortality in locally advanced rectal cancer. To address this, new biomarkers are being developed to predict disease response.

Novel Approaches in the Systemic Management of High-Risk Prostate Cancer.

Locally advanced prostate cancer comprises approximately 20% of new prostate cancer diagnoses. For these patients, international guidelines recommend treatment with radiotherapy (RT) to the prostate in combination with long-term (2-3 years) androgen deprivation therapy (ADT), or radical prostatectomy in combination with extended pelvic lymph node dissection (PLND) as another treatment option for selected patients as part of multimodal therapy. Improvements in overall survival with docetaxel or an androgen receptor signaling inhibitor have been achieved in patients with metastatic castration sensitive or castration resistant prostate cancer. However, the role of systemic therapy combinations for high risk and/or unfavorable prostate cancer is unclear. In this context, the aim of this review is to assess the current evidence for systemic treatment combinations as part of primary definitive therapy in patients with high-risk localized prostate cancer.

Stereotactic body radiation therapy for kidney cancer. Where do we stand?

At present, surgery is still the gold standard for the local treatment of renal cancer. Nonetheless, in several clinical scenarios, stereotactic body radiation therapy (SBRT) also known as stereotactic ablative body radiotherapy (SABR) is emerging as a highly effective ablative technique in fragile patients and those with significant comorbidities, as well as in cases where percutaneous therapy (cryoablation or radiofrequency) is not viable. However, considering the intrinsic radioresistance of renal tumors, the optimal treatment schemes have not been established. In oligometastatic patients, it has been reported that the control of the oligometastases can be a potentially curable approach. Being a technique than can be administered exclusively or in combination with systemic therapy, treatment individualization based on patient characteristics is key. Another scenario under investigation is oligoprogression, where SBRT offers the possibility of delaying further lines of systemic therapy by eliminating subclones of resistant tumor with ablative doses, with the additional opportunity of stimulating the immune system (immunomodulatory role). In this review, we have conducted an analysis of recently published studies that test the role of this technique in different clinical scenarios of this disease. We have found promising results that make SBRT a potent therapeutic approach with low toxicity. We also comment on ongoing studies that will generate the necessary evidence needed for the implementation of this technique in our daily clinical practice.

Radiogenomics in lung cancer: Where are we?

Huge technological and biomedical advances have improved the survival and quality of life of lung cancer patients treated with radiotherapy. However, during treatment planning, a probability that the patient will experience adverse effects is assumed. Radiotoxicity is a complex entity that is largely dose-dependent but also has important intrinsic factors. One of the most studied is the genetic variants that may be associated with susceptibility to the development of adverse effects of radiotherapy. This review aims to present the current status of radiogenomics in lung cancer, integrating results obtained in association studies of SNPs (single nucleotide polymorphisms) related to radiotherapy toxicities. We conclude that despite numerous publications in this field, methodologies and endpoints vary greatly, making comparisons between studies difficult. Analyzing SNPs from the candidate gene approach, together with the study in cohorts limited by the sample size, has complicated the possibility of having validated results. All this delays the incorporation of genetic biomarkers in predictive models for clinical application. Thus, from all analysed SNPs, only 12 have great potential as esophagitis genetic risk factors and deserve further exploration. This review highlights the efforts that have been made to date in the radiogenomic study of radiotoxicity in lung cancer.

Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Prognostic Factors in Locally Advanced Rectal Cancer.

INTRODUCTION: The standard therapy for locally advanced rectal cancer (LARC) is based on neoadjuvant chemoradiotherapy (nCRT) with fluoropyrimidines. There are different biomarkers used as prognostic factors in these tumors. Some studies advocate the use of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as prognostic factors in this clinical scenario. The aim of the study was to evaluate NLR and PLR as prognostic factors of disease-free survival (DFS) and overall survival (OS) and as predictive factors of pathologic complete response (pCR) using Ryan tumor regression scoring system on surgical specimens, in patients with locally advanced rectal adenocarcinoma who received nCRT and radical surgery. METHODS: We retrospectively evaluated patients with locally advanced rectal adenocarcinoma (T3-T4, N1-N3, M0 according to the TNM classification, AJCC 8th edition) who received nCRT based on fluoropyrimidines and radical surgery. Complete blood cell count before nCRT was obtained to calculate NLR and PLR. We made subgroups of patients according to NLR and PLR. We obtained the cut-off point for these ratios based on receiver operating characteristic analysis. We analyzed OS and DFS using the Kaplan-Meier method and Cox proportional hazard models. The relationships between NLR/PLR and pCR, along with other clinical-pathological characteristics, were evaluated by Pearson's χ2 or Fisher's exact test as appropriate. Multivariate analyses were performed using Cox proportional hazard regression models. RESULTS: Between February 2012 and February 2017, 100 consecutive patients were treated according to the reported schedules. Median age was 76 years (68-83). All patients received radiotherapy up to 50.4 Gy and 5-FU-based chemotherapy. 100% completed nCRT and surgery, 38% had elevated basal NLR (cut-off >1.95), and 50% had elevated basal PLR (cut-off >133). After a median follow-up of 72 months (55-88), a lower DFS was obtained in the high NLR subgroup (log-rank, Mantel-Cox 5.165, p = 0.023) and in the high PLR subgroup (log-rank, Mantel-Cox 13.971, p = 0.001). Multivariate analysis showed that PLR (p = 0.006) was a strong significant predictor of DFS. A lower OS was observed in the high NLR and PLR subgroup without significant differences (log-rank, Mantel-Cox 1.245, p = 0.265; 0.578, p = 0.447). No significant differences were obtained in any of the subgroup analysis regarding pCR rates. CONCLUSION: In light of our results, both NLR and PLR could be considered prognostic factors for DFS in patients with LARC that receive treatment with nCRT followed by surgery.

Oligometastatic Hormone-Sensitive Prostate Cancer. Why Radiotherapy?

Androgen deprivation therapy (ADT) has been considered for years the standard initial treatment for patients with metastatic prostate cancer (mPC). Recently published results support the use of taxanes, second-generation antiandrogens or radiotherapy to the primary tumor as part of the treatment in these patients, considering ADT alone as suboptimal. Metastasis-directed therapy (MDT) is used as part of the treatment for oligometastatic patients in different tumor types. In oligometastatic hormone-sensitive prostate cancer the role of MDT is being studied with promising results. In the present review we assess the available evidence for radiotherapy to the primary tumor in newly diagnosed mPC and for MDT in oligometastatic prostate cancer, as well as future directions in this clinical setting.

Role of Radiotherapy and Hormone Therapy in Patients with Node-Positive Locally Advanced Prostate Cancer.

BACKGROUND: New-generation imaging techniques and the increasing use of surgery in high-risk prostate cancer (PCa) allow us to detect many cases of nodal disease at initial diagnosis or after resection. The treatment of PCa with pathologic regional nodes has evolved from the exclusive use of systemic therapy to its combination with locoregional treatment. It can also represent a benefit in the overall survival. However, the evidence from randomised studies is limited. Thus, we review the most relevant results in this scenario. MATERIALS AND METHODS: A literature search was conducted in MEDLINE, PubMed, EMBASE, Clinical-Trials.gov and Web of Science on January 2023 to review node-positive PCa by considering the relevant literature on this topic published with no restrictions on date and language. The search keywords used were "Prostatic Neoplasms" (MeSh) and "Node-positive" (Text Word) and "Radiotherapy" (MeSh) and ("Androgen Antagonists" (MeSh) or "Antineoplastic Agents, Hormonal" (MeSh)), which are indexed within the Medical Subject Headings database. RESULTS: The management of node-positive PCa has no clear definitive consensus at the initial disease diagnosis or after surgery. However, in this review, we summarise the existing literature for the management of these patients in both scenarios, considering imaging tests, radiotherapy, hormone therapy and second-generation hormonal treatments. CONCLUSIONS: The combination of radiotherapy and androgen-deprivation therapy is the treatment of choice. The addition of second-generation hormone therapy, plus the intensification of radiotherapy schedules, will likely change the treatment paradigm for these patients.

Prostate Cancer: Management of Biochemical Recurrence after Surgery.

Radical prostatectomy (RP) is one of the primary treatment options for localised prostate cancer (PCa). Despite its curative intent, 1/3 of patients will experience biochemical recurrence (BCR) during follow-up. Experts have devoted efforts to associate the influence of each individual factor with the risk of BCR to select the optimal treatment for each patient. Optimal management must aim to find a balance between delaying the onset of metastatic disease and overtreating an indolent disease with treatments that can affect quality of life of the patients. Thus far, effective treatment options for men with BCR remain controversial in terms of ideal treatment timing (adjuvant vs. salvage), radiotherapy (RT) fields and doses, selection and duration of systemic therapy and potential synergies between treatments and their therapeutic sequencing. Next-generation imaging techniques, such as Prostate-Specific Membrane Antigen Positron Emission Tomography, are used for early detection of disease progression and exact site of recurrence or progression, thereby enhancing decision making for future disease management. In this review, we evaluate available evidence of controversial topics regarding BCR after RP and explore future directions, such as prognostic and/or predictive factors of response, genetic panels, second-generation hormone treatments, ultra-hypofractionated RT and ongoing clinical trials in this clinical scenario.