Image-Guided Robotic Radiosurgery for the Treatment of Lung Metastases of Renal Cell Carcinoma—A Retrospective, Single Center Analysis

Pulmonary metastases are the most frequent site of metastases in renal cell carcinoma (RCC). Metastases directed treatment remains an important treatment option despite advances in systemic therapies. However, the safety and efficacy of robotic radiosurgery (RRS) for the treatment of lung metastases of RCC remains unclear. Patients with metastatic RCC and lung metastases treated by RRS were retrospectively analyzed for overall survival (OS), progression-free survival (PFS), local recurrence free survival (LRFS) and adverse events. The Kaplan–Meier method was used for survival analysis and the common terminology criteria for adverse events (CTCAE; Version 5.0) classification for assessment of adverse events. A total of 50 patients were included in this study. Median age was 64 (range 45–92) years at the time of RRS. Prior to RRS, 20 patients (40.0%) had received either tyrosine kinase inhibitors or immunotherapy and 27 patients (54.0%) were treatment naïve. In our patient cohort, the median PFS was 13 months (range: 2–93). LRFS was 96.7% after two years with only one patient revealing progressive disease of the treated metastases 13 months after RRS. Median OS was 35 months (range 2–94). Adverse events were documented in six patients (12%) and were limited to grade 2. Fatigue (n = 4) and pneumonitis (n = 2) were observed within 3 months after RRS. In conclusion, RRS is safe and effective for patients with metastatic RCC and pulmonary metastases. Radiation induced pneumonitis is specific in the treatment of pulmonary lesions, but not clinically relevant and survival rates seem favorable in this highly selected patient cohort. Future directions are the implementation of RRS in multimodal treatment approaches for oligometastatic or oligoprogressive disease.

Inhibitory Effects of Doxycycline on Tumor Progression In vitro and on Metastases in Early-Stage Osteosarcoma Xenografts Mice.

Introduction. Osteosarcoma (OS) is the commonest primary osseous malignant tumor with a high propensity to metastasize in lungs. Pulmonary widespread micrometastatic lesions are present in up to 80% of patients at initial diagnosis and they are associated with significantly worse prognosis. Doxycycline (Dox) is a synthetic tetracycline that has been shown to have anti-cancer properties in vitro and in vivo, and inhibit angiogenesis, effects that may prove beneficial for several types of cancer. The aim of the present work was to study how Dox affects OS cells’ growth in vitro and in vivo and OS-driven pulmonary metastasis in vivo. Methods. In vitro, the effect of Dox was measured in MG-63 and 143B human OS cells’ viability, apoptosis, and migration. In vivo, highly metastatic143B cells were orthotopically implanted into the tibia of SCID mice and tumor growth as well as pulmonary metastases between Dox treated and untreated, non-amputated and early amputated xenografts were examined. Results. Dox decreased the viability, inhibited the migration, and induced the apoptosis of OS cells in vitro. In vivo, Dox significantly enhanced tumor necrosis at primary OS sites, similarly to its in vitro effect. It also decreased the expression of Ki67, metalloproteinases 2 and 9 (MMP2 and MMP9), vascular endothelial growth factor A (VEGFA) and Ezrin in primary tumors. It also decreased the circulating VEGFA and MMP9 protein levels, in line with the decreased metastatic burden in Dox-treated mice in both non-amputated and early amputated xenografts. Conclusions. Our results suggest that adjuvant administration of Dox may decrease OS growth and development of pulmonary metastases. Administration of Dox in combination with surgical resection and standard chemotherapeutic protocols in the early-stages of OS treatment is also supported. Moreover, Dox administration prior to the development of clinically detectable pulmonary macrometastases, is associated with enhanced clinically benefits from its anti-metastatic effect.

Metastatic basal cell carcinoma: A report of two cases and a review of the literature

Basal cell carcinomas (BCCs) are among the most common non-melanoma skin cancers in the world. However, given their slowly progressive nature, metastatic BCCs are a relatively uncommon entity. Below, we discuss two separate cases of metastatic BCC that we encountered in our clinical practice. The first is the case of a 57-year-old male with a right cheek BCC and bilateral pulmonary metastases. The second is the case of a 71-year-old male who also presented with a right BCC and pulmonary metastases. We discuss their altered clinical courses. We also conducted a review of the literature focusing on the use of the relatively novel hedgehog inhibitors as a treatment option for individuals diagnosed with metastatic BCC.

Radiomics Study for Discriminating Second Primary Lung Cancers From Pulmonary Metastases in Pulmonary Solid Lesions

BackgroundThe objective of this study was to assess the value of quantitative radiomics features in discriminating second primary lung cancers (SPLCs) from pulmonary metastases (PMs).MethodsThis retrospective study enrolled 252 malignant pulmonary nodules with histopathologically confirmed SPLCs or PMs and randomly assigned them to a training or validation cohort. Clinical data were collected from the electronic medical records system. The imaging and radiomics features of each nodule were extracted from CT images.ResultsA rad-score was generated from the training cohort using the least absolute shrinkage and selection operator regression. A clinical and radiographic model was constructed using the clinical and imaging features selected by univariate and multivariate regression. A nomogram composed of clinical-radiographic factors and a rad-score were developed to validate the discriminative ability. The rad-scores differed significantly between the SPLC and PM groups. Sixteen radiomics features and four clinical-radiographic features were selected to build the final model to differentiate between SPLCs and PMs. The comprehensive clinical radiographic–radiomics model demonstrated good discriminative capacity with an area under the curve of the receiver operating characteristic curve of 0.9421 and 0.9041 in the respective training and validation cohorts. The decision curve analysis demonstrated that the comprehensive model showed a higher clinical value than the model without the rad-score.ConclusionThe proposed model based on clinical data, imaging features, and radiomics features could accurately discriminate SPLCs from PMs. The model thus has the potential to support clinicians in improving decision-making in a noninvasive manner.

Outcomes of Pediatric Patients with metastatic Ewing sarcoma treated with interval compression

Background: Interval compression (IC), defined as 2 week-long cycles of alternating vincristine/doxorubicin/cyclophosphamide and ifosfamide/etoposide, improves survival for localized Ewing sarcoma. The outcomes of patients with metastatic disease treated with IC are uncertain. Methods: We retrospectively reviewed the charts of pediatric patients with metastatic Ewing sarcoma treated with IC at our center between January-2013 and March-2020. We calculated event-free survival and overall survival and used log rank tests for univariate comparisons. Results: We identified 34 patients aged 2.7–17.1 years (median,11.6 years). Twenty-six patients (76%) had pulmonary metastases, and 14 (41%) had extra-pulmonary metastases in the bone (n = 11), lymph nodes (n = 2), and intraspinal tissue (n = 1). All patients received local control therapy: surgery only (n = 7, 21%), radiotherapy only (n = 18, 53%), or both (n = 9, 26%). The estimated 3-year OS and EFS were 62%±9% and 39%±9%, respectively. Patients with pulmonary only metastasis had a 3-year OS of 88%±8% in comparison to those with extra-pulmonary metastasis of 27%±13% (P=0.0074). Survival did not differ according to age group (> vs < 12 years), metastasis site, or primary tumor site, but 3-year event-free survival significantly differed according to local control therapy (surgery only, 83% ± 15%; combined surgery and radiation, 30% ± 18%; radiation only, 15% ± 10%; P = .048). Conclusion: IC yielded similar outcomes for patients with metastatic Ewing sarcoma to that reported in the literature using other regimens. We suggest including this approach to other blocks of therapy

Gemcitabine Maintenance Therapy in Patients With Metastasized Soft Tissue Sarcomas

BackgroundMetastasized soft-tissue sarcomas still pose a significant therapeutic challenge given the limited efficacy of currently available multimodal treatment strategies. Recent progress in molecular characterization of sarcoma subtypes has enabled successful personalized therapy approaches in a minority of selected patients with targetable mutations. However, in the majority of patients with refractory soft tissue sarcomas, long-term survival remains poor.MethodsWe report on three adult patients with various soft tissue sarcomas subjected to Gemcitabine maintenance therapy. Tumor entities included leiomyosarcoma of the pancreas (patient 1), undifferentiated pleomorphic sarcoma of the right femur (patient 2), and peri-aortic leiomyosarcoma (patient 3). Metastatic sites encompassed liver, lung, and bones. All patients received Gemcitabine maintenance therapy until disease progression following prior salvage chemotherapy with Docetaxel and Gemcitabine. Patients were treated outside of clinical trials. Response assessment was based on radiological imaging.ResultsIn response to salvage chemotherapy with Docetaxel and Gemcitabine, one patient exhibited a partial remission, and two patients showed stable disease. Patient 1 exhibited stable disease for 6 months during Gemcitabine maintenance therapy before suffering rapid progression of hepatic metastases. Patient 2 underwent 21 months of Gemcitabine maintenance therapy, which was discontinued after progressive pulmonary metastases were detected. Patient 3 is still being treated with Gemcitabine maintenance therapy. Remarkably, owing to significant chemotherapy-associated hematotoxicity, the dose of Gemcitabine dose was reduced by two-thirds. Nevertheless, stable disease with constant pulmonary metastases has been maintained in this patient for 14 months.ConclusionsGemcitabine maintenance therapy following prior Docetaxel and Gemcitabine chemotherapy is manageable and reveals potential benefits for patients with aggressive metastasized soft tissue sarcomas. Prospective trials evaluating Gemcitabine maintenance therapy are encouraged.

261 A case of metastatic myxoid liposarcoma causing cardiac tamponade

Aims Primary cardiac tumors are generally benign. In one series of over 12 000 autopsies, only seven cases of malignant primary cardiac tumors were identified, for an incidence of less than 0.1%. By comparison, metastatic involvement of the heart is over 20 times more common and has been reported in autopsy series in up to one in five patients dying of cancer. Myxoid liposarcoma (MLS) is the second most common subtype of liposarcoma and it usually occurs in deep tissues of the extremity, especially in the calf or thigh. Some tumors have round cell areas that represent histologic progression to high-grade tumours. Round cells, defined as &gt; 5% of the total cells, are associated with higher malignancy and metastatic potential, resulting in an unfavourable outcome in patients affected. Patients with MLS tend to have metastases to extra pulmonary sites, such as abdominal wall, abdominal cavity, retroperitoneum, and bone, even in the absence of pulmonary metastases. Although several authors have reported a high proportion of extra pulmonary metastases of MLS, cardiac metastasis is extremely rare. Methods and results We present a case of a young woman who underwent resection of calf liposarcoma with the onset of cardiac metastases after 18 years, with cardiac tamponade as a clinical onset. MRI confirmed the cardiac solid mass already evident on CT scan, located along the free anterior wall of the right ventricle in the mid-basal area; the lesion seemed to have pericardial implantation with the free wall of the right ventricle was not well cleaved by the lesion in the Cine-MRI sequences. However it was always visible in the post-contrast sequences without evident protrusion of the lesion into the cavity or signs of thrombosis. The parietal pericardium was located on the periphery of the lesion and was not recognizable in some points. The lesion consisted of two portions, a lower one in which some components with characteristics of adipose signal were recognizable, while the upper one was more solid and vascularized. There was persistence of inhomogeneous and diffuse late enhancement at the lesion level. PET revealed pathological hyper accumulations of radiopharmaceuticals in the heart lesion along the anterior wall of the right ventricle, with central hypocaptation area, possible expression of necrotic-colliquative phenomena. Other hyper accumulations were found in the mediastinal lymph node in the pre-carenal area. These findings were referable to the presence of glucose hyper metabolic tissue of suspected neoplastic significance. The patient temporarily declined surgical excision, but after one month, due to the worsening of her symptoms, she returned to emergency room: The CT scan showed a volumetric increase in cardiac mass with a vertical diameter of 8 cm and adhering to the right ventricle for 7 cm. Thanks to the possibility of surgery, patient underwent exeresis of the capsulated epicardial mass adhering to the anterior wall of the right ventricle and to the pericardium, with removal of the ventricular wall and reconstruction with a bovine pericardium patch and without postoperative complications. Conclusions In MLS the time intervals between the onset of primary disease and cardiac metastasis were reported to be relatively long, ranging from 1 to 25 years. The initial site of metastatic disease in our patient was the heart: she had a solitary cardiac tumour that presented 18 years after the primary surgery in the absence of metastases at other sites. When a cardiac metastasis is found incidentally, it is usually incurable.