Individualized evaluation of risk and prognosis in uterine leiomyosarcoma patients with synchronous distant metastases: a real-world retrospective study.

Background: Uterine leiomyosarcoma (uLMS) accounts for roughly 70% of all uterine sarcomas, with recurrence and mortality rates notably higher than those of other uterine tumors. The prognosis of uLMS patients who have distant metastases remains poor. The objective of this study was to determine independent risk variables related to distant metastases in patients with uLMS and prognostic factors for those with distant metastases. Subsequently, two practical nomograms were developed and validated to assess the probability of distant metastases and predict survival outcomes for these with distant metastases, respectively. Methods: A real-world retrospective study was carried out using data from patients diagnosed with primary uLMS in the Surveillance, Epidemiology, and End Results (SEER) database spanning the years 2010 to 2015. Univariate and multivariate logistic regression analyses were utilized to identify clinicopathological characteristics related to the risk of distant metastases, while univariate and multivariate Cox regressions were employed to determine prognostic factors. Then, a risk nomogram incorporating independent risk variables and a prognostic nomogram integrating independent prognostic factors were established in the training cohort and validated for accuracy in the validation cohort, respectively. Receiver operating characteristic (ROC) curves, area under the curve (AUC), and calibration curves were utilized to measure the accuracy of nomograms, while decision curve analysis (DCA) curves were employed to assess their clinical benefit capacity. Based on the median total point derived from the prognostic nomogram, patients were stratified into high- and low-risk groups. The differentiation ability of the prognostic nomogram was evaluated using Kaplan-Meier survival analysis with the log-rank test. Results: The study encompassed 1,362 patients diagnosed with uLMS, among whom 337 cases (24.7%) manifested synchronous distant metastases at the initial diagnosis. Univariate and multivariate logistic regression analyses identified race, histological grade, T stage, N stage, tumor size, surgery, and chemotherapy as independent risk factors for distant metastases in uLMS patients. The outcomes of both univariate and multivariate Cox analyses indicated that surgery and chemotherapy emerged as independent protective factors for prognosis in uLMS patients with distant metastases, whereas higher histological grade and T stage were identified as independent risk factors. The risk nomogram incorporating independent risk variables and the prognostic nomogram integrating independent prognostic factors could respectively predict the risk of metastases and the prognosis very effectively in both training and validation cohorts. Conclusions: In summary, we developed the novel well-validated risk nomogram to precisely assess the probability of metastases in uLMS patients and prognostic nomogram to predict the prognosis of those with distant metastases, providing decision-making guidance for tailoring individualized clinical management of these patients.

Prostate-specific membrane antigen PET versus [99mTc]Tc-MDP bone scan for diagnosing bone metastasis in prostate cancer: a head-to-head comparative meta-analysis.

Purpose: To evaluate the diagnostic performance of PSMA PET/CT, including [68Ga]Ga-PSMA-11 and [18F]DCFPyL, in comparison with the [99mTc]Tc-MDP bone scan (BS) in identifying bone metastases among prostate cancer patients. Methods: A search was performed in the PubMed and Embase databases to locate pertinent publications from inception to February 12, 2024. The studies included were those that examined the diagnostic effectiveness of PSMA PET/CT (covering [68Ga]Ga-PSMA-11 and [18F]DCFPyL) compared to [99mTc]Tc-MDP BS in identifying bone metastases among prostate cancer patients. The quality of the selected studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) checklist. Results: The meta-analysis included nine articles involving 702 patients. The sensitivity of PSMA PET/CT was higher compared to [99mTc]Tc-MDP BS (0.98 vs. 0.85, P < 0.01), while the specificity of PSMA PET/CT was also higher than [99mTc]Tc-MDP BS (0.97 vs. 0.70,P < 0.01). In subgroup analysis, the sensitivity of [68Ga]Ga-PSMA-11 PET/CT was higher compared to [99mTc]Tc-MDP BS (0.98 vs. 0.86), while the specificity of [68Ga]Ga-PSMA-11 PET/CT was also higher than [99mTc]Tc-MDP BS (0.98 vs. 0.65). Conclusion: Our meta-analysis demonstrates that PSMA PET/CT exhibits superior sensitivity and specificity in comparison with [99mTc]Tc-MDP BS for identifying bone metastases in prostate cancer patients. Further research with head-to-head design is necessary to validate these results and evaluate the clinical effectiveness of these imaging methods. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier PROSPERO CRD42024545112.

Clinical Efficacy of Microwave Ablation Combined with Percutaneous Osteoplasty in the Treatment of Flat Bone Metastases.

Purpose: Evaluating the clinical efficacy and safety of microwave ablation combined with percutaneous osteoplasty (MWA + PO group) versus percutaneous osteoplasty (PO group) for the treatment of flat bone metastases. Methods: Patients with flat bone metastases and intractable pain who underwent PO and/or MWA from January 2016 to January 2023 in our hospital were included, with 36 cases in the MWA+PO group and 21 cases in the PO group. Changes in the visual analog scale (VAS), Oswestry Disability Index (ODI), and quality of life assessment scale(QOL) were evaluated regularly. Postoperative complications and target lesion tumor treatment responses were also observed. Results: The VAS and ODI in both the MWA+PO group and the PO group significantly decreased at 1 week, 1 month, and 3 months postoperatively, The VAS and ODI in the MWA+PO group were lower than those in the PO group postoperatively. The QOL in both the MWA+PO group and the PO group significantly increased at 1 week, 1 month, and 3 months postoperatively, with the QOL in the MWA+PO group being higher than that in the PO group postoperatively. According to the mRECIST criteria (target lesion tumor treatment response), the ORR in the MWA+PO group and PO group was 52.8% and 9.5%, respectively, while the DCR was 94.4% and 57.1%, respectively (P <0.001 and<0.001). Different degrees of bone cement extravasation were observed in both the PO group (38.1%) and MWA+PO group(19.4%)(χ²=2.38, P=0.12), but none of the patients developed clinical symptoms related to bone cement extravasation. The average cost of surgery was ¥10,480.43 higher in the MWA+PO group than in the PO group. Conclusion: The MWA+PO treatment is more effective in relieving patients' local pain, improving local dysfunction, and enhancing quality of life, and can effectively improve target lesion tumor ORR and DCR, but it is also more costly.

Genomic signature for oligometastatic disease in non-small cell lung cancer patients with brain metastases.

Purpose/objectives: Biomarkers for extracranial oligometastatic disease remain elusive and few studies have attempted to correlate genomic data to the presence of true oligometastatic disease. Methods: Patients with non-small cell lung cancer (NSCLC) and brain metastases were identified in our departmental database. Electronic medical records were used to identify patients for whom liquid biopsy-based comprehensive genomic profiling (Guardant Health) was available. Extracranial oligometastatic disease was defined as patients having ≤5 non-brain metastases without diffuse involvement of a single organ. Widespread disease was any spread beyond oligometastatic. Fisher's exact tests were used to screen for mutations statistically associated (p<0.1) with either oligometastatic or widespread extracranial disease. A risk score for the likelihood of oligometastatic disease was generated and correlated to the likelihood of having oligometastatic disease vs widespread disease. For oligometastatic patients, a competing risk analysis was done to assess for cumulative incidence of oligometastatic progression. Cox regression was used to determine association between oligometastatic risk score and oligoprogression. Results: 130 patients met study criteria and were included in the analysis. 51 patients (39%) had extracranial oligometastatic disease. Genetic mutations included in the Guardant panel that were associated (p<0.1) with the presence of oligometastatic disease included ATM, JAK2, MAP2K2, and NTRK1, while ARID1A and CCNE1 were associated with widespread disease. Patients with a positive, neutral and negative risk score for oligometastatic disease had a 78%, 41% and 11.5% likelihood of having oligometastatic disease, respectively (p<0.0001). Overall survival for patients with positive, neutral and negative risk scores for oligometastatic disease was 86% vs 82% vs 64% at 6 months (p=0.2). Oligometastatic risk score was significantly associated with the likelihood of oligoprogression based on the Wald chi-square test. Patients with positive, neutral and negative risk scores for oligometastatic disease had a cumulative incidence of oligometastatic progression of 77% vs 35% vs 33% at 6 months (p=0.03). Conclusions: Elucidation of a genomic signature for extracranial oligometastatic disease derived from non-invasive liquid biopsy appears feasible for NSCLC patients. Patients with this signature exhibited higher rates of early oligoprogression. External validation could lead to a biomarker that has the potential to direct local therapies in oligometastatic patients.

Nivolumab plus ipilimumab with chemotherapy for non-small cell lung cancer with untreated brain metastases: A multicenter single-arm phase 2 trial (NIke, LOGiK 2004).

BACKGROUND: The effect of dual immunotherapy combined with platinum-based chemotherapy on untreated brain metastases derived from non-small cell lung cancer (NSCLC) has remained unclear. METHODS: This multicenter single-arm phase 2 study enrolled patients with chemotherapy-naïve advanced NSCLC and at least one brain metastasis ≥ 5 mm in size that had not been previously treated. Patients received nivolumab plus ipilimumab combined with platinum-doublet chemotherapy (two cycles), followed by nivolumab-ipilimumab alone. The primary endpoint of the study was intracranial response rate as determined by modified Response Evaluation Criteria in Solid Tumors (RECIST) for brain metastases of ≥ 5 mm as target lesions. RESULTS: A total of 30 patients from 18 institutions was enrolled in this study. The median age was 66.5 years (range, 47-83 years), and 26 patients (87 %) had a non-squamous cell carcinoma histology. The median size of all target brain lesions was 8.4 mm, with a range of 5-39 mm. The intracranial response rate assessed by modified RECIST was 50.0 % (95 % CI, 33.2-66.8 %), with the rate of complete response being 20.0 %, and the study met its primary endpoint. The systemic response rate was 53.3 % (95 % CI, 36.1-69.8 %), and responses for intracranial and extracranial lesions were generally consistent. The median intracranial progression-free survival was 8.1 months, and both the median intracranial duration of response and time to brain radiotherapy were not reached. CONCLUSION: Nivolumab plus ipilimumab combined with platinum-based chemotherapy showed promising intracranial activity in NSCLC patients with untreated brain metastases. TRIAL REGISTRATION: jRCT071210019.

A near-infrared fluorescent probe with assembly/aggregation-induced retention effect for specific diagnosis of metastasis and image-guided surgery in breast cancer.

Image-guided surgery is crucial for achieving complete tumor resection, reducing postoperative recurrence and improving patient survival. However, current clinical near-infrared fluorescent probes, such as indocyanine green (ICG), face two main limitations: 1) lack of active tumor targeting, and 2) short retention time in tumors, which restricts real-time imaging during surgery. To address these issues, we developed a near-infrared fluorescent probe capable of in situ nanofiber formation within tumor lesions. This probe actively targets the integrin αvß3 receptors overexpressed on breast cancer cells and exhibits assembly/aggregation-induced retention effects at the tumor site, significantly extending the imaging time window. Additionally, we found that the probe's fluorescence intensity can be enhanced under receptor induction. Due to its excellent tumor specificity and sensitivity, 1FCG-FFGRGD not only identifies primary breast cancer but also precisely locates smaller lymph node metastases and detects sub-millimeter peritoneal metastases. In summary, this near-infrared probe, leveraging assembly/aggregation-induced retention effects, holds substantial potential for various biomedical applications.

Preoperative stereotactic radiotherapy for the management of brain metastases.

Traditionally, postoperative whole-brain radiation therapy (WBRT) has been used for resected brain metastases, reducing local and intracerebral relapses. However, WBRT is associated with cognitive deterioration. Postoperative stereotactic radiotherapy (SRT) has emerged due to its neurocognitive preservation benefits. Despite its advantages, postoperative SRT has several drawbacks, including difficulties in target volume delineation, increased risk of radionecrosis (RN) and leptomeningeal disease (LMD), and prolonged treatment duration. Preoperative SRT has been proposed as a potential alternative, offering promising results in retrospective studies. Retrospective studies have suggested that preoperative SRT could achieve high local control rates with fewer LMD and RN rates compared to postoperative SRT. However, preoperative SRT is primarily based on retrospective data, and no phase 2/3 trials have been published to date. Ongoing clinical trials are expected to provide further insights into the efficacy and safety of preoperative SRT, addressing key questions regarding fractionation, dose, and timing relative to surgery.

Survival outcomes in patients with de novo metastatic Merkel cell carcinoma according to site of metastases.

Introduction: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine malignancy of the skin with a predilection for metastases. This study investigates the clinical outcomes in patients presenting with de novo Stage IV MCC according to the metastatic site(s) at presentation. Materials and methods: Patients who presented with one or more sites of distant metastatic MCC at initial diagnosis between 2009 and 2023 were identified. The presence or absence of one or more metastases in each organ was categorized for each patient at the time of diagnosis. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Competing risk analysis was used to estimate the cumulative occurrence risk of MCC-specific death. Fisher's exact test was used for response rate analysis. Results were considered statically significant if p < 0.05. Results: Thirty-four patients presented with de novo distant metastatic MCC. There was no association between the number of metastatic sites at diagnosis and OS (p= 0.58), PFS (p=0.79), or response rates (p=0.53). However, the presence of bone metastases was associated with significantly shorter OS (8.2 versus 25.2 months, HR: 2.4, 95% CI 1.01-5.7, p= 0.04). MCC-specific death in patients with lymph node metastases was significantly lower than in patients without (HR: 0.28, 95% CI: 0.09-0.87, p= 0.013). The presence of bone metastases tended to associate with an increased risk of MCC-specific death, although not statistically significant. The location of metastases was not associated with the response rate to first-line treatment. There was no significant association between site of metastases and PFS. Conclusion: In this cohort of patients with de novo metastatic MCC, the presence of bone metastases, but not the number of organs involved, was associated with significantly worse OS. The presence of lymph node metastases was associated with lower MCC-specific death. Further research is warranted in larger cohorts to investigate the impact of the location of metastases on clinical outcomes.

Intracranial outcomes following neurosurgical resection in patients with brain metastases secondary to HER2-positive breast cancer versus other subtypes.

PURPOSE: Neurosurgical resection serves an important role in select patients with breast cancer and brain metastases but can delay systemic therapy and yield complications. Consequently, identification of patients most likely to benefit from surgery is important. Given the poorer long-term intracranial responses to radiotherapy sometimes observed in HER2-positive (HER2 +) patients, we investigated whether neurosurgical resection is differentially beneficial in this population. METHODS: We identified 633 patients with newly diagnosed brain metastases arising from breast cancer managed at Brigham and Women's Hospital/Dana-Farber Cancer Institute between 2010 and 2022. Patients were stratified by breast cancer subtype: HER2 + (N = 189), hormone receptor positive (HR +)/HER2- (N = 267), and triple negative (N = 177). Per-patient and per-metastasis outcomes were evaluated; interaction models assessing the impact of neurosurgical resection by subtype were constructed. RESULTS: Relative to HR + /HER2- subtype, omission of upfront neurosurgical resection in patients with HER2 + disease was associated with increased subsequent utilization of salvage stereotactic radiation, whole brain radiotherapy, and craniotomy (interaction HR 2.02 [95% CI, 1.04-3.93], p = 0.04; HR 3.92 [95% CI, 1.24-12.40], p = 0.02; HR 4.98 [95% CI, 1.34-18.58], p = 0.02, respectively). Tumors stemming from HER2 + versus HR + /HER2- primaries displayed increased local recurrence when upfront neurosurgical resection was omitted (interaction HR 3.62 [95% CI, 1.06-12.38], p = 0.04). No such associations were noted when comparing triple negative to HR + /HER2- subtype (p-interaction > 0.05 in all cases). CONCLUSION: Patients with HER2 + disease and brain metastases may disproportionately benefit from upfront neurosurgical resection relative to other subtypes. If validated, our results may suggest a lower threshold to consider surgery in brain metastases secondary to HER2 + breast cancer.

RTOG 0915-compliant patient specific QA for lung stereotactic body radiotherapy using the new PTW 1600SRS detector array.

PURPOSE: An area of focus in radiotherapy is the treatment of oligometastatic lung cancer using highly conformal techniques such as SBRT, performed using VMAT that involves flattening filter free (FFF) beams. This study proposes a new calibration procedure for PTW Octavius 1600SRS detector array and was designed to also evaluate clinical and dosimetric aspects of a patient-specific quality assurance (PSQA) for lung SBRT patients. METHODS: The cohort consists of 20 patients, treated for lung metastases using SBRT with 50 Gy dose in 5 fractions (10 Gy/fr). The proposed calibration method uses only one calibration factor determined at maximum dose rate of 6MV FFF photon beam. The dosimetric accuracy of achieving a high dose gradient was analyzed using the RTOG 0915 protocol and was confirmed by PSQA procedures using the PTW Octavius 1600SRS detector. RESULTS: Conformity index, gradient index, maximum dose at 2 cm and V20 parameters were evaluated with clinical favorable results, with only two plans with lesions situated in the inferior lobe exceeding the deviation allowed for the gradient index. Gamma passing rates using the new calibration method were 98.93% and 99.38% for different gamma criteria of 2 mm/2% and 1 mm/3%, respectively. CONCLUSIONS: The proposed method for calibration using one calibration factor at maximum dose rate for the involved photon beam shows clinically acceptable gamma passing rates. Employing the RTOG 0915 protocol for lung SBRT treatment plan evaluation brings important dosimetric information about treatment plan quality and dose gradient fall-off which can be correlated with the results achieved during the pretreatment verification procedures.

T lymphocyte recruitment to melanoma brain tumors depends on distinct venous vessels.

To improve immunotherapy for brain tumors, it is important to determine the principal intracranial site of T cell recruitment from the bloodstream and their intracranial route to brain tumors. Using intravital microscopy in mouse models of intracranial melanoma, we discovered that circulating T cells preferably adhered and extravasated at a distinct type of venous blood vessel in the tumor vicinity, peritumoral venous vessels (PVVs). Other vascular structures were excluded as alternative T cell routes to intracranial melanomas. Anti-PD-1/CTLA-4 immune checkpoint inhibitors increased intracranial T cell motility, facilitating migration from PVVs to the tumor and subsequently inhibiting intracranial tumor growth. The endothelial adhesion molecule ICAM-1 was particularly expressed on PVVs, and, in samples of human brain metastases, ICAM-1 positivity of PVV-like vessels correlated with intratumoral T cell infiltration. These findings uncover a distinct mechanism by which the immune system can access and control brain tumors and potentially influence other brain pathologies.

Computed tomographic features of pulmonary and extrapulmonary lesions can be useful in prioritizing the diagnosis of hemangiosarcoma metastases in dogs.

OBJECTIVE: The aim of this study was to evaluate the CT features of pulmonary metastases in dogs with hemangiosarcoma (HSA) at various sites. Additionally, the CT characteristics of extrapulmonary metastases in the same population were assessed. METHODS: Retrospective, observational, and descriptive study conducted from April 2013 to January 2024. Dogs with histologically confirmed HSA and suspected or cytologically/histologically confirmed lung metastases were included. Dogs were excluded if they had a second primary tumor or only 1 unsampled pulmonary nodule. RESULTS: 33 dogs were included, with 26/33 [78.8%] having more than 10 metastatic pulmonary nodules. Most nodules were generalized (24/33 [72.7%]), miliary (29/33 [87.9%]) to subcentimetric (32/33 [97%]) in size, well-defined margins (29/33 [87.9%]), or a perilesional halo sign (24/33 [72.7%]). When more than 10 nodules were present, a generalized distribution was prevalent, while a peripheral location was more common when 2 to 10 nodules were present (P < .0001). In 32/33 (97%) cases, a pulmonary vessel was directly connected to the nodule (feeding vessel). After contrast administration, most lung metastases appeared homogenous (26/33 [78.8%]), although some showed areas of intense enhancement (5/33 [15.1%]) a feature also observed in extrapulmonary metastases with varying frequency (0% to 85.7%). CONCLUSIONS: Pulmonary HSA metastases were characterized by generalized, small (miliary/subcentimetric), well-defined nodules, commonly associated with a halo sign and feeding vessel. Intralesional areas of spotty postcontrast linear or amorphous strong hyperdensity were frequently observed especially in extrapulmonary metastases. CLINICAL RELEVANCE: These features may help radiologists and clinicians orient their diagnosis toward metastatic HSA.

First-line treatment of EGFR-mutated non-small cell lung cancer with brain metastases: a systematic review and meta-analysis.

This systematic review and network meta-analysis evaluates first-line treatment options for patients with EGFR-mutant non-small cell lung cancer (NSCLC) and brain metastases. We analyzed 24 randomized controlled trials (RCTs) involving 2,682 patients, comparing various EGFR tyrosine kinase inhibitors (TKIs) and combination therapies. Direct comparisons showed that the addition of bevacizumab or chemotherapy to first-generation (1G) EGFR-TKIs improved overall survival (OS) compared to 1G TKIs alone, with HRs of 0.704 (95% CI: 0.433-0.973) and 0.682 (95% CI: 0.464-0.899), respectively. However, third-generation (3G) TKI monotherapy did not significantly improve OS compared with 1G TKIs, with an HR of 0.855 (95% CI: 0.511-1.198). Indirect comparisons suggested that the combination of 3G TKIs with chemotherapy provided the most significant improvements in OS and progression-free survival (PFS), significantly outperforming 3G TKIs, with HRs of OS 1.69 (95% CI: 1.14-3.4) and PFS 2.13 (95% CI: 1.28-3.54). Intracranial PFS was best with 1G TKIs plus bevacizumab. Our findings suggest that 3G EGFR-TKIs in combination with chemotherapy may be the most effective strategy for patients with EGFR-mutant NSCLC and brain metastases, though further head-to-head trials are needed for validation.

The Optimal First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer Based on Liver Metastasis Status: A Network Meta-Analysis and Systematic Review.

PURPOSE: To compare the efficacy of first-line regimens based on programmed cell death (or ligand) [PD-(L)1] blockade in extensive-stage small-cell lung cancer (ES-SCLC) patients with or without liver metastases (LM), and to identify optimal treatment strategies. METHODS: Network meta-analysis of randomized controlled trials (RCTs) comparing chemo-immunotherapy (CIT) and chemotherapy (CT) in ES-SCLC patients stratified by LM. Overall survival (OS) and progression-free survival (PFS) were evaluated using hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Seven RCTs involving 3658 ES-SCLC patients (1243 with LM, 2415 without LM) were analyzed. For patients with LM, the combination therapies of anti-PD-1 + CT (HR, 0.67; 95% CI, 0.54%-0.82%; p < 0.001) and anti-PD-L1 + CT + anti-angiogenesis (HR, 0.84; 95% CI, 0.71%-0.99%; p = 0.042) demonstrated superior efficacy in prolonging OS compared to CT alone. The anti-PD-1 + CT regimen had the highest cumulative probability of 91.6% for extending OS in patients with LM. For patients without LM, all CIT regimens resulted in improved OS compared to CT alone, with the regimen of anti-angiogenesis + anti-PD-L1 + CT ranking first and having the highest cumulative probability of 95.5% for prolonging OS. CONCLUSIONS: CIT is effective for ES-SCLC patients regardless of LM status. For patients with LM, PD-1 blockade combined with CT is the best option. For patients without LM, the most beneficial regimen is the combination of anti-angiogenesis, PD-L1 blockade, and CT.

The combination of transarterial chemoembolization and microwave ablation is superior to microwave ablation alone for liver metastases from colorectal cancer.

OBJECTIVES: This study aimed to compare the combination therapy of transarterial chemoembolization (TACE) and microwave ablation (MWA) with MWA alone in treating liver metastases from colorectal cancer (LMCRC). MATERIALS AND METHODS: In this retrospective study, a total of 251 patients with unresectable and not to chemotherapy responding LMCRC were included. Group A consisted of 184 patients (104 male and 80 females; mean age: 64 ± 11.4 years) with 442 metastases who received a combination of TACE and MWA. A total of 67 patients (49 male and 18 females; mean age: 63.2 ± 11.8 years) with 173 metastases patients were included in group B, who received only MWA. Parameters assessed were local tumor progression (LTP), hepatic distant tumor progression (hDTP), hepatic progression-free survival (hPFS), and overall survival (OS). RESULTS: The rate of LTP was 4.9% in group A and 4.5% in group B (p-value: 0.062). The rate of hDTP was 71.7% and 83.6% for groups A and B (p-value: 0.81), respectively. The mean hPFS was 13.8 months (95% CI 10.9-16.8) for group A and 8.1 months (95% CI 6.1-10.1) for group B (p-value: 0.03). The median OS time for group A was 30 months (95% CI 26-34), with 1-, 2-, 3-, and 4-year OS rates of 84.2%, 61.1%, 40.8% and 31.3%, respectively. In group B however, the median OS time was 26 months (95% CI 18-34) with 1-, 2-, 3-, and 4-year OS rates of 82.3%, 53.2%, 34.6% and 28.2%, respectively (p-value: 0.67). CONCLUSION: The combination therapy of TACE and MWA is superior to the monotherapy of MWA for LMCRC, especially regarding hDTP, hPFS and OS.

Predicting the survival of patients with painful tumours treated with palliative radiotherapy: a secondary analysis using the 3-variable number-of-risk-factors model.

BACKGROUND: The 3-variable number-of-risk-factors (NRF) model is a prognostic tool for patients undergoing palliative radiotherapy (PRT). However, there is little research on the NRF model for patients with painful non-bone-metastasis tumours treated with PRT, and the efficacy of the NRF model in predicting survival is unclear to date. Therefore, we aimed to assess the prognostic accuracy of a 3-variable NRF model in patients undergoing PRT for bone and non- bone-metastasis tumours. METHODS: This was a secondary analysis of studies on PRT for bone-metastasis (BM) and PRT for miscellaneous painful tumours (MPTs), including non-BM tumours. Patients were grouped in the NRF model and survival was compared between groups. Discrimination was evaluated using a time-independent C-index and a time-dependent area under the receiver operating characteristic curve (AUROC). A calibration curve was used to assess the agreement between predicted and observed survival. RESULTS: We analysed 485 patients in the BM group and 302 patients in the MPT group. The median survival times in the BM group for groups I, II, and III were 35.1, 10.1, and 3.3 months, respectively (P < 0.001), while in the MPT group, they were 22.1, 9.5, and 4.6 months, respectively (P < 0.001). The C-index was 0.689 in the BM group and 0.625 in the MPT group. In the BM group, time-dependent AUROCs over 2 to 24 months ranged from 0.738 to 0.765, while in the MPT group, they ranged from 0.650 to 0.689, with both groups showing consistent accuracy over time. The calibration curve showed a reasonable agreement between the predicted and observed survival. CONCLUSIONS: The NRF model predicted survival moderately well in both the BM and MPT groups.

Radiofrequency ablation: mechanisms and clinical applications.

Radiofrequency ablation (RFA), a form of thermal ablation, employs localized heat to induce protein denaturation in tissue cells, resulting in cell death. It has emerged as a viable treatment option for patients who are ineligible for surgery in various diseases, particularly liver cancer and other tumor-related conditions. In addition to directly eliminating tumor cells, RFA also induces alterations in the infiltrating cells within the tumor microenvironment (TME), which can significantly impact treatment outcomes. Moreover, incomplete RFA (iRFA) may lead to tumor recurrence and metastasis. The current challenge is to enhance the efficacy of RFA by elucidating its underlying mechanisms. This review discusses the clinical applications of RFA in treating various diseases and the mechanisms that contribute to the survival and invasion of tumor cells following iRFA, including the roles of heat shock proteins, hypoxia, and autophagy. Additionally, we analyze| the changes occurring in infiltrating cells within the TME after iRFA. Finally, we provide a comprehensive summary of clinical trials involving RFA in conjunction with other treatment modalities in the field of cancer therapy, aiming to offer novel insights and references for improving the effectiveness of RFA.

Large Pleural Metastases With Significant Inter-fractional Volume Reduction During Online Adaptive Radiotherapy: A Case Report With Dosimetry Comparison.

Online adaptive radiotherapy (oART) dose calculation relies on synthetic computed tomography (sCT), which notably influences anatomical changes. This study elucidates how sCT may respond to significant inter-fractional tumor volume reduction and its subsequent impact on dose distribution. In this case report, we exported sCT and cone-beam CT (CBCT) images from each treatment session. We retrospectively analyzed 20 adaptive and scheduled plans of a patient receiving oART for large pleural metastases with notable inter-fractional tumor regression. By overriding the CT number of the dissipated tumor volume with that of the lungs on each sCT, we recalculated each plan. We compared the dose distribution between the adaptive and scheduled plans. Percentage dose difference and 3D gamma analysis were employed to assess dose variability. Results of the dose analysis showed that, compared to the online (non-overridden) plans, the recalculated plans using overridden sCT demonstrated right-shifted dose-volume histogram curves for the targets and right lung, with a slight but statistically significant increase of no less than 1.5% in D mean and D max for the targets and right lung. The location of hotspots shifted in alignment with tumor shrinkage and beam arrangement. Both recalculated adaptive and scheduled plans achieved ideal GTV, CTV, and PTV coverage, with adaptive plans significantly reducing the dose and irradiated volume to the right lung. In conclusion, as the pleural tumor volume decreased, online plans slightly underestimated the dose distribution and shifted the location of hotspots, though this remained clinically acceptable. Importantly, adaptive plans significantly minimized the irradiated volume of the critical OAR (right lung) while ensuring optimal dose coverage of the target volume, demonstrating the potential of sCT and adaptive oART to enhance treatment precision and efficacy in dynamically changing tumor environments.

Factors associated with the distribution of brain metastases in lung cancer: a retrospective study.

The distribution of brain metastases (BMs) in patients with lung cancer may be associated with the primary tumor-related factors and cerebral small vascular diseases (CSVDs). The aim of this study was to investigate the potential effects of the above factors on the distribution of BMs. A total of 5,788 lesions in 823 patients with BMs from lung cancer were enrolled. The numbers of BMs and CSVDs in 15 brain regions were determined. CSVDs include recent small subcortical infarcts (RSSIs), perivascular spaces, and lacunes of presumed vascular origin (LPVOs). We collected the number of CSVDs, and primary tumor-related factors (including clinical and imaging features) in lung cancer patients with BMs. Univariate and multivariate linear regression were utilized to analyze the potential influence of the above factors on the number of BMs in 15 brain regions. In addition, we performed subgroup analyses of all patients with adenocarcinoma (AD), female patients with AD, male patients with AD, and patients with small cell lung cancer. Univariate linear regression analyses showed that bone metastasis, adrenal metastasis, RSSIs, and LPVOs were associated with the number of BMs in over half of the examined brain regions. Only the independent association of LVPOs persisted in the multivariate linear regression analyses, and similar phenomenon was found in the subgroup analyses. In conclusion, the distribution of BMs in lung cancer patients appears to be associated with the presence of LVPOs, while primary tumor-related factors have less influence.

Return to work in younger patients with brain metastases who survived for 2 years or more.

PURPOSE: The study's purpose was to analyze return to work and other long-term outcomes in younger patients with newly diagnosed brain metastases, treated before they reached legal retirement age, i.e. younger than 65 years. METHODS: We included patients who survived greater than 2 years after their first treatment, regardless of approach (systemic therapy, neurosurgical resection, whole-brain or stereotactic radiotherapy). The primary endpoint was the proportion of patients who worked 2 years after their initial treatment for brain metastases. Outcomes beyond the 2-year cut-off were also abstracted from comprehensive electronic health records, throughout the follow-up period. RESULTS: Of 455 patients who received active therapy for brain metastases, 62 (14%) survived for > 2 years. Twenty-eight were younger than 65 years. The actuarial median survival was 81 months and the 5-year survival rate 53%. For patients alive after 5 years, the 10-year survival rate was 54%. At diagnosis, 25% of patients (7 of 28) were permanently incapacitated for work/retired. Of the remaining 21 patients, 33% did work 2 years later. However, several of these patients went on to receive disability pension afterwards. Eventually, 19% continued working in the longer run. Younger age, absence of extracranial metastases, presence of a single brain metastasis, and Karnofsky performance status 90-100 were common features of patients who worked after 2 years. CONCLUSION: Long-term survival was achieved after vastly different therapeutic approaches, regarding both upfront and sequential management. Many patients required three or more lines of brain-directed treatment. Few patients continued working in the longer run.