Search Results (178)

Background/Objectives: The global population of individuals aged ≥ 80 years is rapidly growing, leading to an increasing incidence of cancer diagnoses in this age group. While stereotactic body radiotherapy (SBRT) has proven effective in treating pulmonary oligometastases, patients over 80 remain underrepresented in clinical analyses. This study aimed to evaluate clinical outcomes and toxicity of SBRT for pulmonary oligometastases in octogenarians. Methods: This retrospective, single-centre analysis included 34 patients aged ≥ 80 years treated with SBRT for histologically confirmed pulmonary oligometastases between 2010 and 2024. Results: A total of 46 pulmonary metastases were treated with curative intent using fractionation schemes of 3 × 15 Gy, 6 × 8 Gy, or 10 × 6 Gy. Median biologically effective dose (BED10) was 112.5 Gy. Follow-up included regular CT imaging and toxicity assessment according to CTCAE. With a median follow-up of 22.6 months, 1-, 2-, and 3-year local control (LC) rates were 95.2%, 95.2%, and 90.2%, respectively. Median overall survival (OS) was 46.6 months, with 1-, 2-, and 3-year OS rates of 78.4%, 71.4%, and 59.5%. Progression-free survival (PFS) at 1, 2, and 3 years was 63.4%, 51.6%, and 47.3%, respectively. No grade ≥ 3 toxicities were observed. Grade 2 pneumonitis and dermatitis occurred in 2.9% each and were well managed. Asymptomatic rib fractures were detected in 5.9% of patients. No significant predictors for LC, PFS, or OS were identified in univariate analysis. Conclusions: SBRT for pulmonary oligometastases in patients ≥ 80 years is feasible, safe, and effective. High local control, favourable cancer-specific survival, and minimal toxicity support its use as a curative-intent treatment in this growing patient population. These findings contribute important site- and age-specific evidence and support the inclusion of very elderly patients in future prospective SBRT trials. Full article

Extracranial metastases from meningiomas are extremely rare, with an incidence of <1%, and their prognosis is poor. Moreover, there is currently no gold standard for their treatment; therefore, the decision-making process is strictly dependent on multidisciplinary discussions. In this report, we describe the case of a 73-year-old patient who was diagnosed with a solitary lung metastasis more than 20 years after the initial treatment for a low-grade meningioma. Molecular characterization of this metastasis was performed using the Oncomine Comprehensive Assay Plus, which identified multiple functional mutations in the beta2-microglobulin (β2M) and ATM genes, both of which may contribute to immune evasion and genomic instability. A short overview of the literature is also reported. To our knowledge, no previous reports exist on single pulmonary metastasis from low-grade meningioma occurring more than 20 years after diagnosis. Full article

Background and Objective: Due to the increasing use of imaging and lung cancer screening programs, the rate of detected pulmonary nodules has steadily increased over the past decade. Overall, the diagnosis and management of pulmonary nodules remain challenging. Moreover, no specific guidelines exist for the management of pulmonary nodules in patients with a history of previous malignancy. This study reflects the current management in a real-world setting in a specialized European center. Methods: In this retrospective single-center study, patients with a pulmonary nodule <3 cm referred to the Division of Pulmonology or the Department of Thoracic Surgery at the Medical University of Vienna, Austria, from November 2022 to July 2024, were analyzed. A subgroup analysis of patients with a history of previous malignancy was performed and compared to patients without previous malignancies. Results: In total, 356 patients (48.5% male, median age 67 years [IQR 61–74], 53.7% with a history of previous cancer) with a pulmonary nodule (mean size of 14.8 mm) were enrolled. Bronchoscopy, computed tomography (CT)-guided biopsy, or surgery was performed in 13.2%, 7.3%, and 65.2% of the cases, respectively. The overall malignancy rate was 70.5%. Pulmonary nodules in patients with a prior malignancy were significantly larger (p < 0.001), showed a progression in size (p < 0.001), and were found to be malignant more frequently when compared to patients without previous cancer (p = 0.032). Conclusions: As most patients referred to a specialized center represent a selected group of high-risk patients, the majority of pulmonary nodules were found to be malignant. In patients with a history of previous malignancy, tissue sampling is warranted as the rate of malignancy is high. Full article

Pulmonary metastasectomy for colorectal cancer represents a key component in modern oncological surgery, balancing precision resection with systemic disease management. Despite ongoing debate initiated by randomized trials, the surgical removal of lung metastases continues to offer significant survival benefits in well-selected patients. This review synthesizes the evolving landscape of pulmonary metastasectomy, integrating classical prognostic indicators, such as the disease-free interval (DFI) and carcinoembryonic antigen (CEA) levels, with emerging molecular insights including KRAS and BRAF mutations. The relationship between surgical radicality, systemic therapies, and personalized genetic profiling is redefining patient selection and optimizing outcomes. By dissecting recent evidence and ongoing controversies, we clarify the complex decision-making required to navigate this complex clinical terrain. Ultimately, the synergy of multidisciplinary care and precision surgery holds the promise of durable disease control and extended survival in colorectal cancer patients with lung metastases. Full article

Background/Objectives: TTF-1 and Napsin A are immunohistochemical markers that are widely used for the diagnosis of lung adenocarcinomas or thyroid carcinomas, as well as the characterization of metastases. However, several publications have reported the aberrant expression of one or both markers in extrathoracic malignancies, including gastrointestinal adenocarcinomas. The goal of our study was to determine the frequency of TTF-1- and Napsin A-positive neoplasms in cohorts consisting of esophageal, gastric and colorectal adenocarcinomas. Methods: Buffered formalin-fixed paraffin-embedded tumor tissues from 854 patients with primary resected gastrointestinal and esophageal carcinomas were placed in tissue microarrays (TMAs) for investigation. Between two and six tumor cores were analyzed for each case. For immunohistochemical staining, we used TTF-1 (SPT24 clone) and Napsin A (IP64 clone). Tumors were considered positive if at least 5% of their tumor cells showed weak nuclear (TTF-1) or cytoplasmic (Napsin A) staining. Results: In total, 16 cases showed positive staining for TTF-1, alongside 7 cases for Napsin A. The greatest proportion of TTF-1- and/or Napsin A-positive tumors was found among esophageal adenocarcinomas (5/125 cases; 4%). Co-expression of TTF-1 and Napsin A was found in five cases, including three esophageal and two gastric adenocarcinomas. In colorectal carcinomas, co-expression of these markers was not detected. Conclusions: TTF-1 and Napsin A are useful immunohistochemical makers for establishing the diagnosis of pulmonary adenocarcinoma. Additionally, knowing that a proportion of gastrointestinal neoplasms express these markers can help to avoid diagnostic misinterpretations. Full article

Background: Fat embolism and fat embolism syndrome are rare but well-known consequences of long bone fractures and orthopedic surgeries. These sources support the mechanical theory of their development. On the other hand, as an alternative pathway suggested by the biochemical theory, lipase activation and fat breakdown are also a possible background for lipid droplets appearing in the vasculature. According to Hulman’s theory, elevated C-reactive protein levels can facilitate calcium-dependent agglutination of very low-density proteins and chylomicrons forming fat globules. The level of this acute-phase protein can increase mainly in advanced-stage cancers but also has predictive or indicative value in treatment success. Methods: This study focused on strictly selected patients with different histological types and origins of cancer, as well as advanced cancer in approximately 90% of the deceased. After collecting the tissue samples, the frozen sections were stained with Oil Red O to detect fat emboli. Results: Less than 50% of the cases showed punctiform, non-clinically relevant pulmonary fat embolism, and fat embolism syndrome was identified in none of the cases. In one, non-advanced cancer case, punctiform kidney fat embolism was observed. Conclusions: The end-of-life anergic state of patients may influence the procedure. In the case of osseous metastases, since the intramedullary sinuses are affected, both the mechanical and the biochemical backgrounds may prevail and mediate fat embolism formation. Full article

Background/Objectives: Granular cell tumors (GCTs) are rare neurogenic tumors with Schwann cell differentiation. Although most are benign, 1–2% exhibit malignant behavior. The imaging features of GCTs remain poorly characterized due to their rarity and anatomic variability. This study aims to elucidate the manifestations of GCTs in multimodal imaging across different anatomic locations. Methods: We retrospectively analyzed 66 histopathologically confirmed GCT cases (2011–2024), assessing their clinical presentations, pathological characteristics, and imaging findings from ultrasound (n = 31), CT (n = 14), MRI (n = 8), and endoscopy (n = 15). Two radiologists independently reviewed the imaging features (location, size, morphology, signal/density, and enhancement). Results: The cohort (mean age: 42 ± 12 years; 72.7% female) showed tendency in location towards soft tissue (48.4%), the digestive tract (30.3%), the respiratory system (7.6%), the breasts (7.6%), and the sellar region (6.1%). Six cases (9.1%) were malignant. The key imaging findings by modality were as follows: Ultrasound: Well-circumscribed hypoechoic masses in soft tissue (96.1%) and irregular margins in the breasts (80%, BI-RADS 4B) were found. MRI: The sellar GCTs exhibited T1-isointensity, variable T2-signals (with 50% showing “star-like crack signs”), and heterogeneous enhancements. The soft tissue GCTs were T1-hypointense (75%) with variable T2-signals. CT: Pulmonary/laryngeal GCTs appeared as well-defined hypodense masses with mild/moderate enhancements. Endoscopy: Submucosal/muscularis hypoechoic nodules with smooth surfaces were found. Malignant GCTs were larger (mean: 93 mm vs. 30 mm) but lacked pathognomonic imaging features. Three malignant cases demonstrated metastases. Conclusions: GCTs exhibit distinct imaging patterns based on their anatomical location. While certain features (e.g., star-like crack signs) are suggestive, imaging cannot reliably differentiate benign from malignant variants. Histopathological confirmation remains essential to diagnosis, particularly given the potential for malignant transformations (at 9.1% in our series). Multimodal imaging guides the localization and biopsy planning, but clinical–radiological–pathological correlation is crucial for the optimal management. Full article

TGF-β is a central mediator of pulmonary allergic inflammation recently associated with lung metastasis of osteosarcoma. Given the controversial links between cancer and allergic diseases, this study aimed to evaluate the effects of allergic airway inflammation—particularly TGF-β—on osteosarcoma lung metastasis using a comorbidity mouse model. Osteosarcoma cells were implanted in BALB/c mice with induced allergic airway inflammation. Lung metastasis was quantified, while PCNA/TGF-β expression was assessed by immunohistochemistry and digital pathology. Bioinformatic analyses of patient datasets compared TGF-β and PCNA expression in metastatic vs. normal tissues, and their association with survival. Mice with allergic inflammation showed increased lung metastases associated with TGF-β production. In patient samples, both TGF-β and PCNA were upregulated in metastatic tissues and correlated with poor overall survival. PCNA was also linked to genes involved in cell proliferation, DNA replication, and repair. Our results show an association between allergic airway inflammation and extensive lung metastasis of osteosarcoma in a comorbidity mouse model with elevated expression of TGF-β and PCNA. Full article

Background/Objectives: Early treatment assessment in metastatic renal cell carcinoma (mRCC) remains challenging due to the limited accuracy of current imaging methods. Given prostate-specific membrane antigen (PSMA) overexpression in mRCC, PSMA PET is a promising approach. Despite numerous studies on PSMA imaging in mRCC, data on PSMA uptake changes during systemic therapy are scarce. We analyzed PSMA uptake on PET after treatment initiation in mRCC patients. Methods: A retrospective single-center analysis of mRCC patients who underwent [¹⁸F]PSMA-1007 PET/CT before (PET₁) and at a mean of 9.5 weeks after (PET₂) starting systemic therapy was conducted. PSMA uptake in metastatic lesions was compared by region and RCC subtype. Uptake differences between PET₁ and PET₂ were analyzed using an unpaired t-test. Results: This study included 25 patients (mean age 65.2 ± 14.7 years; 20 male) with mRCC. A total of 113 (PET₁) and 48 (PET₂) metastases were assessed. Lymph node metastases showed stable PSMA uptake (median SUV_max) after treatment (7.8 vs. 7.7, p = 0.77), while uptake by bone (6.4 vs. 12.4, p = 0.03) and lung metastases (4.5 vs. 8.1, p = 0.004) increased significantly. SUV stability in lymph nodes was independent of RCC subtype (ccRCC: p = 0.48, pRCC: p > 0.99). Bone (6.6 vs. 15.9, p = 0.008) and lung metastases (4.8 vs. 8.1, p = 0.02) had higher PSMA uptake in ccRCC, unlike pRCC (bone: 6.2 vs. 6.0, p = 0.86). Conclusions: Alterations of PSMA-radioligand uptake are seen in bone and pulmonary metastases but not in lymph node metastases after initiation of systemic treatment in patients with mRCC. ccRCC has a higher PSMA uptake than other RCC subtypes. Full article

Background/Objectives: Malignant melanoma (MM) is an aggressive neoplasm with a rising global incidence. Accurate staging and risk stratification are essential for guiding therapeutic decisions and improving patient prognosis. [18F]-FDG PET-CT enables the non-invasive assessment of tumor metabolic activity, offering a valuable adjunct to histopathological evaluation. However, the correlation between PET-CT findings and established prognostic markers in MM, such as Breslow thickness, ulceration, and mitotic rate, remains insufficiently explored. Methods: This retrospective observational study included 61 patients diagnosed with MM, of whom 48 met the inclusion criteria. Quantitative and qualitative variables such as SULmax, Breslow thickness, Ki-67 expression, and mitotic rate were analyzed using descriptive statistics, while correlations between PET-CT findings, SLNB, and histopathological characteristics were assessed using Spearman’s correlation test. A p-value < 0.05 was considered statistically significant. Results: Significant associations were identified between ulceration and both overall metastases (p = 0.01) and pulmonary metastases (p = 0.02). Breslow thickness showed a positive correlation with metastatic spread (p = 0.01), reinforcing its role as a key prognostic indicator. Perineural and vascular invasion were significantly associated with intra-abdominal metastases (p < 0.001 and p = 0.0007, respectively). Tumor-infiltrating lymphocytes (TILs) were inversely correlated with intra-abdominal metastases (p = 0.05), while sentinel lymph node positivity correlated with the presence of regional (p = 0.008) and distant (p = 0.02) metastases. Additionally, subcutaneous SULmax values were significantly higher in male patients compared to females (p = 0.04). Conclusions: Integrating PET-CT metabolic parameters with histopathological markers enhances the assessment of MM aggressiveness and metastatic potential. By refining risk stratification, PET-CT may contribute to personalized therapeutic strategies and improved patient management in MM. Full article

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by extreme ultraviolet (UV) sensitivity, predisposing patients to multiple cutaneous malignancies. We present the case of a 26-year-old male with XP diagnosed with three distinct skin cancers: superficial spreading melanoma (SSM), basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Among these, the melanoma had metastasized. A computed tomography (CT) scan revealed a suspicious pulmonary nodule, prompting further metabolic characterization via positron emission tomography/computed tomography (PET/CT) with ¹⁸F-fluorodeoxyglucose ([¹⁸F]FDG). The scan detected significant hypermetabolism not only in the lung lesion but also in an unsuspected right parotid gland lesion, refining disease staging and guiding treatment decisions. The patient underwent immunotherapy with nivolumab, achieving a complete metabolic response in both metastatic lesions, as confirmed by follow-up PET/CT. This case underscores the critical role of [¹⁸F]FDG PET/CT in staging and treatment monitoring for selected patients with XP, a population in which advanced imaging is rarely employed. Moreover, the patient’s remarkable response to immunotherapy suggests a potential link between XP-related DNA repair defects and increased sensitivity to PD-1 blockade. These findings highlight the importance of integrating metabolic imaging into XP management and warrant further investigation into the immunogenicity of XP-associated malignancies. Full article

Liver metastases from soft tissue sarcoma (STS) (excluding gastrointestinal stromal tumors) are rare and more commonly arise from retroperitoneal and intra-abdominal primary sites. Chemotherapy remains the mainstay of treatment for disseminated disease, but its effectiveness is limited and patients typically have a dismal prognosis with short survival. However, when metastases are confined to the liver (without pulmonary involvement), some patients may benefit from local techniques, either surgical or nonsurgical, that can provide long periods of disease-free survival. Due to the rarity of STS, especially with liver metastases, and the heterogeneity of histologies and biological behavior, there is a lack of standardized treatment guidelines and universally accepted criteria for this specific setting. To fill this gap, a multidisciplinary working group of experts in sarcoma and liver surgery reviewed the literature and available evidence and developed a set of clinical recommendations to be voted and discussed in the I Ibero-American Consensus on the Management of Metastatic Sarcoma, held at the III Spanish-Portuguese Update Meeting on the Treatment of Sarcomas in May 2024. Herein, the voting results of this meeting and the resulting consensus recommendations are presented, and their applicability, strengths, and limitations are discussed. Full article

Background and Objectives: CDK4/6 inhibitors (CDK4/6i) have revolutionized the treatment of hormone receptor-positive HER2 negative (HR(+)/HER2(-)) breast cancer. Despite their efficacy, interstitial lung disease (ILD) remains a rare but potentially fatal adverse effect. This study aims to evaluate the incidence and clinical characteristics of ILD associated with CDK4/6 inhibitors in breast cancer patients in Turkey. Materials and Methods: A retrospective multicenter analysis included 464 breast cancer patients treated with CDK4/6 inhibitors between January 2017 and April 2024. Patients receiving ribociclib or palbociclib were evaluated for the development of ILD. Radiological assessments were performed to confirm ILD and exclude other conditions. Clinical characteristics, treatment regimens, and outcomes were analyzed. Results: ILD was identified in 10 patients (2.1%). The average age of the affected patients was 62.5 ± 9.85 years. Hypersensitivity pneumonitis and nonspecific interstitial pneumonia (NSIP) were the most common radiological patterns. Palbociclib was implicated in six cases, while ribociclib was associated with four cases. Grade 3 pulmonary toxicity was observed in eight patients, and Grade 4 toxicity in two patients. One patient who was on palbociclib died due to ILD. No significant correlation was found between ILD and age, smoking status, lung metastases, or prior thoracic radiotherapy. Conclusions: The incidence of CDK4/6 inhibitor-associated ILD in Turkish breast cancer patients appears higher than previously reported in clinical trials. More robust, long-term studies are necessary to identify potential risk factors and mitigate ILD-related mortality. Full article

Background: Preclinical studies on liposomal interleukin (IL) therapy demonstrate considerable promise in cancer treatment. This review explores the achievements, challenges, and future potential of liposomal IL encapsulation, focusing on preclinical studies. Methods: A structured search was conducted using the PubMed and Web of Science databases with the following search terms and Boolean operators: (“liposomal interleukin” OR “liposome-encapsulated interleukin”) AND (“gene therapy” OR “gene delivery”) AND (“cancer” OR “tumor” OR “oncology”) AND (“pre-clinical studies” OR “animal models” OR “in vitro studies”. Results: Liposomal IL-2 formulations are notable for enhancing delivery and retention at tumor sites. Recombinant human interleukin (rhIL-2) adsorbed onto small liposomes (35–50 nm) substantially reduces metastases in murine models. Hepatic metastasis models demonstrate superior efficacy of liposomal IL-2 over free IL-2 by enhancing immune responses, particularly in the liver. Localized delivery strategies, including nebulized liposomal IL-2 in canine pulmonary metastases and intrathoracic administration in murine sarcoma models, reduce systemic toxicity while promoting immune activation and tumor regression. Liposomal IL gene therapy, delivering cytokine genes directly to tumor sites, represents a notable advancement. Combining IL-2 gene therapy with other cytokines, including IL-6 or double-stranded RNA adjuvants, synergistically enhances macrophage and T-cell activation. Liposomal IL-4, IL-6, and IL-21 therapies show potential across various tumor types. Pairing liposomal IL-2 with chemotherapy or immune agents improves remission and survival. Innovative strategies, including PEGylation and ligand-targeted systems, optimize delivery, release, and therapeutic outcomes. Conclusions: Utilizing immune-stimulatory ILs through advanced liposomal delivery and gene therapy establishes a strong foundation for advancing cancer immunotherapy. Full article

Objective: Colorectal pulmonary metastasis is the most common resected metastatic disease of the lung. Pulmonary metastasectomy (PM) for colorectal oligometastases is a well-established intervention with curative intent. Local recurrence at the resection site in the lung is a problem, with an impact on survival. The use of a 1320 nm neodymium:yttrium aluminum garnet (Nd:YAG) laser causes the vaporization and coagulation at the resection line and thereby increases safety margins around the nodule. We aimed to evaluate the local recurrence rate after laser-assisted pulmonary metastasectomy (LPM) for colorectal metastases. Methods: We conducted a retrospective analysis of 49 patients treated with laser-assisted pulmonary metastasectomy for 139 metastatic nodules from colorectal cancer from 2010 to 2018. All nodules were resected using Nd:YAG 1320 nm laser, aiming for a safety margin of five mm. The minimum follow-up time after PM was 24 months. Results: Local intrapulmonary recurrence developed at 7 of the 139 (5.0%) resection sites in 5 of the 49 patients (10.2%). Microscopically incomplete resection was a significant risk factor for recurrence (p = 0.023). Larger nodule size (>12 mm) negatively impacted local recurrence (p = 0.024). Nodules larger or equal to 12 mm in size also lowered the patients’ probability of survival by 67.29% (HR: 0.3271, 95% CI: 0.1265–0.846, p = 0.018). Conclusions: The rate of local recurrence at the resection site after LPM for colorectal metastases is low. Complete resection is a positive predictor of survival without local recurrence. Microscopic complete resection with the addition of vaporization and coagulation at the resection margin seems to be sufficient to prevent local recurrence. However, larger nodules may require larger safety margins. Full article