Spinal metastases can cause disabling pain and neurological deterioration and have historically been treated with palliative intent and conventional external beam radiotherapy (cEBRT). A fundamental shift away from the short-term palliative goals associated with cEBRT has taken place over the past two decades following the availability of stereotactic body radiotherapy (SBRT). This technique has enabled durable pain relief and local control owing to the ability to precisely deliver high radiation doses across typically up to five fractions, with level 1 evidence supporting superior complete pain response rates and local tumour control compared with cEBRT. The development of spinal SBRT has also resulted in greater multidisciplinary collaboration, with neuroradiologists, spinal surgeons, interventional radiologists, biomechanical engineers, medical physicists, medical oncologists and radiation oncologists working together with the common goal of improving our understanding of the pathophysiology and treatment of spinal metastases. As a result, substantial gains have been realized in refining patient selection and treatment sequencing, and particularly the development of less-invasive surgical procedures. In this Review, we summarize the development and role of SBRT in the management of spinal metastases.

Primary hepatic undifferentiated carcinoma is an extremely rare and aggressive malignancy with no established systemic therapy, and the efficacy of immune checkpoint inhibitors (ICIs) remains unknown. We report a 67-year-old man with compensated hepatitis C-related cirrhosis who presented with a 27 mm segment 8 liver lesion and lymph node and bone metastases. Liver biopsy revealed undifferentiated carcinoma with high programmed death-ligand 1 (PD-L1) expression, and combination therapy with durvalumab and tremelimumab (Dur/Tre) was initiated. Shortly after treatment, the patient developed cranial nerve palsies (III, VII, VIII), suspected to represent either an immune-related adverse event or Ramsay Hunt syndrome; his symptoms improved with prednisolone and valaciclovir, allowing Dur/Tre to be resumed. After four courses, partial tumor shrinkage was achieved, and after 17 courses the primary tumor had decreased to 10 mm with complete resolution of nodal metastases, without further significant adverse events. To our knowledge, this is the first report of primary hepatic undifferentiated carcinoma with high PD-L1 expression demonstrating a sustained response to Dur/Tre. This case suggests that PD-L1 expression may serve as a potential biomarker for predicting ICI responsiveness in this rare and aggressive tumor.

RICTOR, a scaffold protein of the mTORC2 complex, regulates AKT signaling and has been implicated in tumor progression and therapy resistance across multiple cancers. However, the prognostic impact of RICTOR mutations in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma remains unclear. This study aimed to evaluate the clinicopathological, molecular, and survival characteristics of patients with metastatic EGFR-mutant lung adenocarcinoma according to RICTOR mutation status. We retrospectively analyzed 235 patients diagnosed with de novo metastatic lung adenocarcinoma between 2018 and 2024 across three tertiary oncology centers. Patients with targetable oncogenic drivers other than EGFR (ALK, ROS1, HER2, KRAS G12C, BRAF V600E, RET, MET) were excluded. Next-generation sequencing (NGS) was performed using a hybrid-capture panel (Illumina TSO500). Clinical features, co-mutations, treatment responses, and overall survival (OS) were compared between RICTOR-mutant and wild-type subgroups within the EGFR-mutant cohort. Survival analyses employed Kaplan-Meier estimates, log-rank tests, and Cox regression modeling. Of the total cohort, 39 patients (17%) had EGFR-mutant tumors, of whom 15 (38%) carried RICTOR mutations. RICTOR-mutant cases were more likely to be former smokers and presented more frequently with bone and pleural metastases compared with wild type. Treatment patterns and RECIST v1.1 response rates did not significantly differ between groups. Median OS was significantly shorter in RICTOR-mutant versus RICTOR-wild patients (8 vs. 14 months, log-rank p < 0.001). In univariate analysis, RICTOR mutations were associated with inferior OS (HR 2.48, 95% CI 1.73-7.95, p = 0.03), and this association remained significant in multivariate analysis (HR 2.34, 95% CI 1.69-6.75, p = 0.021). Exploratory analyses suggested that RICTOR co-mutations with EGFR exon 19 deletions, exon 18 alterations, or exon 20 alterations were associated with poorer survival outcomes. RICTOR mutations were associated with a high-risk subset of EGFR-mutant metastatic lung adenocarcinoma characterized by more aggressive clinical features and worse survival. These findings suggest the need for prospective validation and support the potential integration of RICTOR status into molecular risk stratification frameworks for precision oncology.

Esophageal cancer usually shows focal intense FDG uptake on FDG PET. Diffuse FDG uptake pattern of the esophageal cancer has been rarely reported. We describe FDG PET/CT findings in a case of poorly differentiated esophageal squamous cell carcinoma diffusely involving the entire esophagus. FDG PET/CT showed diffuse irregular thickening of the entire esophageal wall with diffusely intense FDG uptake with SUVmax of 15 and multiple FDG-avid lymph nodes and osteolytic bone metastases.

A 68-year-old woman with cervical cancer and pulmonary metastases presented with limb paresthesia and pain one week after chemotherapy. Whole-body bone scintigraphy performed to evaluate for bone metastases revealed rib metastases, along with poor visualization of the right distal lower extremity, raising suspicion for possible arterial flow obstruction in the right lower limb. Further imaging confirmed extensive thrombosis in the right common iliac artery and its distal branches. This case suggests that decreased uptake in the skeletal structures and surrounding soft tissues on whole-body bone scintigraphy may indicate a risk of arterial thrombosis.

Herein, we report the case of a woman in her mid-forties with stage IIB cervical squamous cancer status post-chemoradiation and brachytherapy with curative intent one year prior, who subsequently presented with lacy red to violaceous patches on the forehead, abdomen, back, and legs, as well as mildly tender, ill-defined, purpuric dermal nodules on the right upper back and right inner thigh. Hypercoagulability work-up was negative, and biopsy was consistent with metastatic, intravascular squamous cell carcinoma of cervical origin. This prompted repeat imaging, which was suspicious for metastatic disease to lymph nodes, lungs, and pericardium with multiple bilateral acute/subacute embolic brain infarcts and left ventricular thrombus, and the patient was subsequently started on pembrolizumab, carboplatin, and paclitaxel. Dermatology recommended warming the skin during infusions to promote vasodilation and improve intravascular medication distribution. Despite almost complete resolution of purpuric skin findings and initial improvement in metastatic bone and lymph node disease, the patient had disease progression with worsening bone and new leptomeningeal metastases, as well as subcutaneous metastatic nodules, and was switched to second-line immunotherapy, tisotumab and bevacizumab. Unfortunately, the patient continued to have progressive metastatic disease, leading to multiple complications and hospitalizations, and was ultimately transitioned to hospice care. She passed eleven months post-presentation. Our case highlights the importance of considering retiform purpura as a rare manifestation of intravascular metastases in patients with cervical squamous cell carcinoma, the value of cutaneous metastases in the management of oncologic patients, and the need to further assess the prognostic utility of cutaneous metastases in the era of immunotherapy, which, based on our case, appears to remain a poor prognostic sign.

IntroductionChemo-immunotherapy is the standard frontline treatment of advanced non-squamous non-small cell lung cancer (nsq-NSCLC). Among oncogenic drivers, KRAS mutation accounts for approximately 25% of lung adenocarcinomas, with p.G12C being the most common variant. This study assessed clinical features and survival outcomes according to KRAS mutation in a real-life population of nsq-NSCLC patients treated with first-line platinum-pemetrexed-pembrolizumab.MethodsThis is a retrospective-prospective study including patients with nsq-NSCLC who received first-line platinum-pemetrexed-pembrolizumab from 4 September 2018 in 33 Italian Centers.ResultsAmong the 765 patients included in this analysis, 121 (15.8%) had KRAS p.G12C mutation, 201 (26.3%) KRAS non-p.G12C mutation and 443 (57.9%) KRAS WT. KRAS-mutated patients had more frequently a history of smoking (90.6% vs 84.1%, p=0.012) and bone metastases (44.1% vs 35.9%; p=0.022) compared to KRAS WT.Median Overall Survival (OS) was similar between KRAS-mutated and KRAS WT patients (16.7 vs 18.2 months; adjusted Hazard Ratio [HR] 1.19, 95% Confidence Interval [CI] 0.95-1.50, p=0.132). No difference in OS was found between KRAS p.G12C and KRAS non-p.G12C (15.9 vs 17.0 months, HR 0.93, 95% CI: 0.66-1.31, p=0.676).Median progression-free survival was significantly shorter in KRAS-mutated compared to KRAS WT patients (8.8 vs 10.8 months; adjusted HR 1.29, 95% CI 1.04-1.59, p=0.018), with no differences between KRAS p.G12C and KRAS non-p.G12C (8.8 vs 8.8 months, HR 0.95, 95% CI: 0.70-1.30, p=0.756).ConclusionsKRAS mutation showed a potential negative predictive role in advanced nsq-NSCLC treated with first-line chemo-immunotherapy. The impact of co-mutations and post-progression outcomes warrants further investigation.

IntroductionBone metastasis in breast cancer patients can lead to poor quality of life and cause significant morbidity. First-line treatments for bone metastases include bone modifying agents that inhibit osteoclast activity to reduce bone resorption. The most commonly used bone modifying agents include zoledronic acid and denosumab. It is currently unknown whether a therapy change from zoledronic acid to denosumab would result in greater symptom control or improved disease outcomes in breast cancer patients. In this single institution retrospective cohort study, we aimed to identify the reasons why patients transitioned from zoledronic acid to denosumab and to determine whether denosumab, as a second-line therapy, led to reduced narcotic use for metastatic bone pain.Materials and MethodsBreast cancer patients with bone metastases treated at The Ohio State University Comprehensive Cancer center from 2011-2018 with a bone modifying agent were examined. Nineteen patients who received second-line denosumab following previous exposure to zoledronic acid were identified and included in this study.ResultsThe two most common reasons patients switched from zoledronic acid to denosumab were related to side effect burden (28%) and bone metastasis progression (28%). No reduction in narcotic use due to bone pain was observed six months after starting denosumab. None of the patients developed new skeletal related events after switching to Denosumab.ConclusionOverall, denosumab as a second-line therapy appeared to be well-tolerated in our cohort, as we did not observe any treatment-related toxicity. Patients who switched to denosumab did not experience improved pain control.

Osteocytes, once viewed mainly as passive bone-embedded cells, are now recognized as active regulators of the metastatic bone niche. Emerging evidence indicates that these cells integrate mechanical, inflammatory, and tumor-derived cues to influence metastatic seeding, dormancy, reactivation, and lesion progression in bone. This review synthesizes current understanding of osteocyte contributions to skeletal metastasis. We discuss core signaling axes, including osteocyte-derived RANKL/OPG balance, Wnt antagonists (sclerostin/DKK1), mechanotransduction pathways (Piezo1 signaling and connexin-43 hemichannels), and osteocyte paracrine mediators (extracellular vesicles and senescence-associated factors), and examine how each axis modulates tumor cell dormancy, osteolysis, or osteoblastic progression. We then review translational strategies targeting osteocytes, recent preclinical and clinical insights. Emerging biomarkers (e.g., serum sclerostin, DKK1, bone turnover markers) and immune-skeletal imaging approaches are also considered. Controversies, including the paradoxical effects of sclerostin blockade and the identity of in vivo RANKL sources, are discussed. Finally, we outline key knowledge gaps and propose endpoints for future trials. In summary, an osteocyte-centric perspective reveals novel targets and strategies for managing bone metastases, guiding future translational research.

Introduction: Inflammatory and immune-based prognostic markers such as the Lung Immune Prognostic Index (LIPI) and the Glasgow Prognostic Score (GPS) have gained increasing attention in ES-SCLC, particularly in patients receiving first-line chemoimmunotherapy. However, no prior study has explored a broader, integrated inflammatory framework that evaluates these parameters collectively. Methods: We retrospectively evaluated 166 patients with ES-SCLC treated with first-line platinum-etoposide plus atezolizumab or durvalumab between 2019 and 2025. LIPI could be calculated in 123 patients based on available dNLR and LDH values, while GPS and the Combined Inflammatory Prognostic Score (CIPS) could be assessed in 120 patients with accessible CRP and albumin data. Results: Median PFS and OS were 8.16 and 15.96 months, respectively. In univariate analyses, poor ECOG PS, liver and bone metastases, poor LIPI, poor GPS, and high-risk CIPS were associated with shorter PFS and OS. In multivariate analysis, only LIPI and GPS remained independent predictors of both PFS and OS, while ECOG PS was independently associated with OS. Although CIPS demonstrated clear prognostic separation in univariate analysis, it did not retain independent significance, likely due to sample size limitations and overlap with LIPI and GPS components. Conclusions: LIPI and GPS are strong independent prognostic markers in ES-SCLC receiving chemoimmunotherapy. While CIPS did not demonstrate independent prognostic value in multivariate analysis, its simplicity, balanced two-tier design, and use of routinely available biomarkers highlight its potential clinical utility. To our knowledge, this is the first study to assess a combined inflammatory prognostic model in this population. Prospective multicenter validation is warranted.