Osseous Metastases Research Articles

Single-center experience of PD1 inhibition in metastatic uveal melanoma.

87 Background: Metastatic uveal melanoma (MUM) is a rare histology with poor prognosis. Therapies used in cutaneous melanoma with success have limited to no efficacy in uveal melanoma. Limited data exists regarding the efficacy of PD-1 inhibition in this disease. Methods: Patients carrying a diagnosis of MUM that had been treated with any PD1 inhibitor at the Cleveland Clinic were analyzed. Median overall survival from the diagnosis of metastatic disease and from the start of PD-1 inhibition were calculated. RECIST 1.1 criteria were used to assess response to therapy. Results: 10 patients with MUM have been treated with a PD1 inhibitor. Mean age at initiation of PD1 inhibition was 74. Five (50%) were female. Median time from initial diagnosis to metastatic disease was 67 months (range, 5-204). All 6 patients with a genetic profiling result available were classified as poor risk either by cytogenetics or gene expression profiling. Median overall survival from diagnosis of metastatic disease was 24 months (range, 9-46). Six patients had also been treated with ipilimumab, 4 had prior treatment, 1 had PD-1 prior to ipilimumab, and one had concurrent treatment with combination ipilimumab/nivolumab. Adjunct local radiation occurred in 6 patients: 5 of the liver (4 embolization, 1 SBRT), one of osseous metastases. Median time on PD1 treatment was 2 months (range, 1-6). Two patients had SD, 6 PD, 3 have not yet been reevaluated. Median survival from initiation of PD1 inhibition was 9 months (range, 7-12). Adverse events were as expected from published experiences with PD-1 inhibition. All patients with median survival from initial diagnosis of metastatic disease over one year received both PD-1 and CTLA-4 inhibition as well as radiation. Conclusions: In this single center experience, no patients had tumor response to PD-1 inhibition. Combination therapies may be worth exploring in the treatment of MUM.

Clinical profile of carcinoma breast cases at a tertiary care hospital

Background: Breast carcinoma is a serious health problem and is among the major health issues in India. Also, it has a relatively early age presentation in this part of the world. Present study describes the features like age at presentation, clinical stage at presentation and incidence of regional lymph node involvement and distant metastases among the breast cancer patients at Government Medical College, Jabalpur in Madhya Pradesh, India.Methods: This hospital-based descriptive study was conducted at the Department of Surgery, Government Medical College, Jabalpur in Madhya Pradesh state of India. Fifty patients with a confirmed diagnosis of breast cancer were included in the study. The details like age at presentation, clinical stage at presentation and incidence of regional lymph node involvement and distant metastases among the breast cancer patients were described and tabulated.Results: Youngest patient of the series was aged 30 years whereas the oldest was aged 65 years. Maximum patients belonged to 41 to 50 years age group. Stage wise distribution of cases reflected that Stage III was the most common stage at presentation. Majority of the cases had lymph node involvement (90%). Liver metastasis was seen in 8 cases (16%), of which, 2 cases had ascites. There were 6 cases of lung metastasis, of which 2 cases had pleural effusion and remaining 4 cases showed solitary metastasis. 6 cases of osseous metastasis were observed, out of which, 2 cases had skull metastasis and 4 cases had spine involvement.Conclusions: It was found that the age group in majority of the patients was younger as compared to Western world and this finding is in line with data from India and other Asian regions. Also, there was a presentation at a later stage of disease in our study population.

The role of cytoreductive radical prostatectomy (cRP) in men with hormone-sensitive, metastatic prostate cancer (mPCA).

241 Background: Androgen deprivation represents the standard treatment for PCA with osseous metastases. We explored the role of cRP in the largest cohort of contemporary patients with mPCA treated in 4 tertiary referral centres. Methods: A total of 114 patients with mPCA, lymph node, osseous or visceral metastases underwent cRP. Surgery related complications (Clavien-Dindo classification) and functional outcome were analysed. Oncologic outcome parameters such as cancer specific & overall survival as well as biochemical and clinical-free survival were evaluated using descriptive statistical analysis. Results: Mean patient age was 61 (42-69) years. Mean and median follow-up was 39.7 months (7-75) and 47 months (28-96), resp. 93 (81.6%) and 21 (18.4%) patients had low volume and high volume mets, resp.,. 80(70.2%) pts underwent neoadjuvant ADT with LHRH analogues. Surgical approach was open retropubic RP in 104 (92%) pts and 2 (1.8%), 10 (8.8%) and 101 (89.4%) pts underwent no, limited or extended pelvic LAD, resp. Adjuvant therapy was delivered in 99 (86.8%) pts. Pathohistology revealed significant vital PCA in 100% of cases: n = 16 (14.0%) exhibited pT4a, n = 21 (18.4%) had pT2 and the remainder had pT3a/b PCA. Positive lymph nodes or positive surgical margins were identified in 61.6% and 36.8%, resp.. 110 (96.5%) are alive and 66.7% are relapse-free. 74 (64.9%) pts did not experience any surgery related complications; 15 (13.1%) pts experienced Clavien Dindo grade IIIb/IV complications and underwent reintervention. Low versus high volume (32.2% vs 50%, p = 0.03), PSA at cRP < 1ng/ml vs PSA > 4 ng/ml, (18.9% vs 45.6%, p = 0.02) were associated with relapse. Low vs high volume disease (7.1% vs 32.1%), PSA < 4ng/ml vs PSA > 4 ng/ml (6.1% vs 47.8%) and neoadjuvant vs no neoadjuvant therapy (8.75% vs 24.2%) were associated with Clavien-Dindo IIIB complications (p < 0.05). Conclusions: cRP is feasible in men with mPCA independent on the extent of disease with a low rate of significant complications and good functional outcome. About two thirds of the patients remain relapse-free after a median follow-up of close to 4 years. cRP might be an individualized treatment option in the multimodality management of mPCA.

Pulmonary Kaposi Sarcoma with Osseous Metastases in an Human Immunodeficiency Virus (HIV) Patient: A Remarkable Response to Highly Active Antiretroviral Therapy

Patient: Male, 34Final Diagnosis: Pulmonary Kaposi’s sarcoma with bony metastatsesSymptoms: Cough • weight lossMedication: —Clinical Procedure: —Specialty: Infectious DiseasesObjective:Rare diseaseBackground:Kaposi sarcoma (KS) is known to involve the mucocutaneous tissues and the aero-digestive tracts. In acquired immune deficiency syndrome (AIDS) patients, KS has an aggressive course and carries poor prognosis. We present a case of pulmonary KS with osseous metastases as the first presentation of human immunodeficiency virus (HIV) infection in a young male. The lesions impressively decreased in size and numbers following initiation of highly active antiretroviral therapy (HAART).Case Report:A 34-year-old heterosexual male presented with a one month history of cough and 15–20 pound weight loss within six months. Examination revealed oral thrush, decreased breath sounds and crackles on the right lower lung base. Imaging showed a large right perihilar mass with multiple lytic lesions involving thoracic and lumber vertebrae, ribs, sternum, and clavicles. Blood and sputum cultures, smears for acid fast bacilli, and a QUANTIferon gold test were all negative. He tested positive for HIV and his CD4 count was 7 cells/uL. Bronchoscopy with biopsy was unrevealing. Pathology of the right hilar mass was diagnostic of KS. Following initiation of antiretroviral therapy his condition dramatically improved; repeat chest CT scan showed marked regression of the bony and pulmonary lesions.Conclusions:The dual action of HAART on the recovery of the immune system and against human herpes virus 8 (HHV-8) may essentially cause regression of KS lesions.

Bone-specific poly(ethylene sodium phosphate)-bearing biodegradable nanoparticles

Chemotherapy is the most reliable treatment for osteoporosis and osseous metastases. To facilitate better drug delivery for bone treatments, a novel preparation of polymeric nanoparticles with high affinity to bone has been prepared. Two-step synthesis of cholesteryl-functionalized poly(ethylene sodium phosphate) (Ch-PEPn·Na) was performed via ring-opening polymerization of cyclic phosphoesters and the demethylation. The molecular weight of Ch-PEPn·Na could be well controlled by changing the ratio of cholesterol and cyclic phosphoesters. Because Ch-PEPn·Na exhibits an amphiphilic nature in aqueous media, Ch-PEPn·Na-bearing nanoparticles (PEPn·Na NPs) were prepared by a solvent evaporation technique. The size of the nanoparticles investigated in the current study is approximately 100nm, which was determined by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Due to the presence of highly water-soluble polymer chains, dispersion of PEPn·Na NPs in aqueous media was stable for at least 1 week. Hemolytic activity of PEPn·Na NPs was found to be low and PEPn·Na NPs did not disintegrate mammalian cell membranes. Additionally, cytotoxicity of PEPn·Na NPs was not observed at concentrations below 100μg/mL. The adsorption of PEPn·Na NPs on hydroxyapatite (HAp) microparticles was studied in comparison with poly(ethylene glycol) nanoparticles (PEG NPs). Both PEPn·Na NPs and PEG NPs adsorbed well onto HAp microparticles in distilled water with binding equilibrium constants (KHAp) for PEPn·Na NPs and PEG NPs of 3.6×106 and 7.9×106, respectively. In contrast, only PEPn·Na NPs adsorbed onto HAp microparticles in a saline phosphate buffer. Moreover, the adsorption of PEPn·Na NPs onto HAp microparticles occurred even in the presence of 1.2mM calcium ions or low-pH media. The affinity of the nanoparticles to bovine bone slices was also studied, with the result that large quantities of adsorbed PEPn·Na NPs were observed on the slices by scanning electron microscope.

EPCR promotes breast cancer progression by altering SPOCK1/testican 1-mediated 3D growth

BackgroundActivated protein C/endothelial protein C receptor (APC/EPCR) axis is physiologically involved in anticoagulant and cytoprotective activities in endothelial cells. Emerging evidence indicates that EPCR also plays a role in breast stemness and human tumorigenesis. Yet, its contribution to breast cancer progression and metastasis has not been elucidated.MethodsTranscriptomic status of EPCR was examined in a cohort of 286 breast cancer patients. Cell growth kinetics was evaluated in control and EPCR and SPARC/osteonectin, Cwcv, and kazal-like domains proteoglycan (SPOCK1/testican 1) silenced breast cancer cells in 2D, 3D, and in co-culture conditions. Orthotopic tumor growth and lung and osseous metastases were evaluated in several human and murine xenograft breast cancer models. Tumor-stroma interactions were further studied in vivo by immunohistochemistry and flow cytometry. An EPCR-induced gene signature was identified by microarray analysis.ResultsAnalysis of a cohort of breast cancer patients revealed an association of high EPCR levels with adverse clinical outcome. Interestingly, EPCR knockdown did not affect cell growth kinetics in 2D but significantly reduced cell growth in 3D cultures. Using several human and murine xenograft breast cancer models, we showed that EPCR silencing reduced primary tumor growth and secondary outgrowths at metastatic sites, including the skeleton and the lungs. Interestingly, these effects were independent of APC ligand stimulation in vitro and in vivo. Transcriptomic analysis of EPCR-silenced tumors unveiled an effect mediated by matricellular secreted proteoglycan SPOCK1/testican 1. Interestingly, SPOCK1 silencing suppressed in vitro 3D growth. Moreover, SPOCK1 ablation severely decreased orthotopic tumor growth and reduced bone metastatic osteolytic tumors. High SPOCK1 levels were also associated with poor clinical outcome in a subset breast cancer patients. Our results suggest that EPCR through SPOCK1 confers a cell growth advantage in 3D promoting breast tumorigenesis and metastasis.ConclusionsEPCR represents a clinically relevant factor associated with poor outcome and a novel vulnerability to develop combination therapies for breast cancer patients.

Osseous metastases of chordoma: imaging and clinical findings.

To describe the imaging and clinical characteristics of chordoma osseous metastases (COM). Our study was IRB approved and HIPAA compliant. A retrospective search of our pathology database for pathology-proven COM yielded 15 patients who had undergone MRI, CT, bone scan, and/or FDG-PET/CT. The imaging and clinical features of the COMs were recorded. A control group of age and gender matched chordoma patients without osseous metastasis was evaluated. The COM mean maximal dimension was 6.4 ± 4.0cm. The majority (60%) of patients had one lesion. Extra-osseous soft tissue component was present in 85% and was larger than intra-osseous component in 76%. On MRI the lesions were heterogeneous but predominantly T2 hyperintense with hypointense septae, and with variable enhancement. On CT the lesions were typically destructive or permeative; calcifications were rare. The extent of the soft tissue component was isodense to muscle on CT and therefore better evaluated on MRI. COM was in a body part contiguous to the site of the primary tumor. Compared to the controls, COM patients were more likely to have local recurrence (P = 0.0009) and positive resection margins (P = 0.002). At 1year, 33% of COM patients were deceased and 13% had progressive metastases. COM are associated with large extra-osseous soft tissue components, which are better visualized by MRI. They are often located in a body part contiguous to the site of the primary tumor, portend poor prognosis, and are associated with positive resection margins and local recurrence.

Triage of Limited Versus Extensive Disease on 18F-FDG PET/CT Scan in Small Cell lung Cancer.

Objective(s):Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma, which accounts for 10-15% of pulmonary cancers and exhibits early metastatic spread. This study aimed to determine the added value of 18F-FDG PET/CT imaging in tumor, node, and metastasis (TNM) staging of SCLC, compared to the conventional computed tomography (CT) scan and its potential role as a prognosticator.Methods:This retrospective review was conducted on 23 patients, who were histopathologically diagnosed to have SCLC and referred for undergoing 18F-FDG PET/CT scanning during October 2009-December 2015. The rate of agreement between the CT and 18F-FDG PET/CT findings for TNM staging was calculated using the Cohen’s kappa (κ). The median follow-up time was eight months, ranging 27-3 months). The overall and disease-free survival rates were calculated based on the extent of disease.Results:19 cases were male and four female with the mean age of 58±9 years. The 18F-FDG PET/CT identified limited and extensive diseases in 2 (8.7%) and 21 (91.3%) patients, respectively. In addition, the results of the Cohen’s kappa demonstrated a strong (κ=0.82), fair (κ=0.24), and poor (κ=0.12) agreement between the PET/CT and CT findings for determining tumor, node, and metastasis stages, respectively. The 18F-FDG PET/CT scans upstaged disease in 47% of the cases with visceral and osseous metastasis. The disease-free survival rates for the limited and extensive diseases were 100% and 23% within the 12-month follow-up. In addition, 8 (35%) patients expired during the follow-up period.Conclusion:Improved nodal and metastatic disease identification highlights the role of 18F-FDG PET/CT scanning in initial staging of SCLC with prognostic implications.

Increased renal parenchymal retention of 99mTc-MDP (hot kidneys) in two patients of Hepatocellular Cancer: one with and other without osseous metastases

Background: Hepatocellular cancer (HCC) is the fifth-leading cancer in men worldwide. Here we present two HCC patients who showed high diffuse renal parenchymal retention of 99mTc MDP on bone scan. Cases presentation: Bone scan with 99mTc MDP was performed on two known HCC patients, which showed skeletal metastases in one and absent in the other case. Their kidneys showed high renal parenchymal retention of tracer with kidneys looking much HOT than adjacent bones. The differential diagnosis of hot kidneys include nephrocalcinosis, hypercalcemia, hyperparathyroidism, chemotherapy, sickle cell disease, acute renal injury, recent radiotherapy and aluminum breakthrough of 99Mo-99mTc generator. Our patients did not fit in any of these. Hot kidneys in patient with liver cirrhosis have been reported due to hepatorenal syndrome. Although chronic liver parenchymal disease was present in the background of HCC, but our patients were not having hepatorenal syndrome (normal renal function tests). Quality control of generator and MDP vials used showed absence of any aluminum breakthrough and labeling efficiency was greater than 95% respectively. So, the exact cause of hot kidneys in these cases cannot be ascertained and some altered metabolism in liver and hemodynamic changes in body due to HCC might be the cause. Conclusion: High diffuse renal parenchymal retention of 99mTc MDP might be seen on bone scan in HCC cases. Its clinical significance is unknown and needs further research to find out its exact mechanism and cause.

Dynamic contrast-enhanced magnetic resonance imaging of osseous spine metastasis before and 1 hour after high-dose image-guided radiation therapy.

OBJECTIVE High-dose image-guided radiation therapy (HD IGRT) has been instrumental in mitigating some limitations of conventional RT. The recent emergence of dynamic contrast-enhanced (DCE) MRI to investigate tumor physiology can be used to verify the response of human tumors to HD IGRT. The purpose of this study was to evaluate the near-immediate effects of HD IGRT on spine metastases through the use of DCE MRI perfusion studies. METHODS Six patients with spine metastases from prostate, thyroid, and renal cell carcinoma who underwent HD IGRT were studied using DCE MRI prior to and 1 hour after HD IGRT. The DCE perfusion parameters plasma volume (Vp) and vascular permeability (Ktrans) were measured to assess the near-immediate and long-term tumor response. A Mann-Whitney U-test was performed to compare significant changes (at p ≤ 0.05) in perfusion parameters before and after RT. RESULTS The authors observed a precipitous drop in Vp within 1 hour of HD IGRT, with a mean decrease of 65.2%. A significant difference was found between Vp values for before and 1 hour after RT (p ≤ 0.05). No significant change was seen in Vp (p = 0.31) and Ktrans (p = 0.1) from 1 hour after RT to the first follow-up. CONCLUSIONS The data suggest that there is an immediate effect of HD IGRT on the vascularity of spine metastases, as demonstrated by a precipitous decrease in Vp. The DCE MRI studies can detect such changes within 1 hour after RT, and findings are concordant with existing animal models.

SURVIVAL IMPACT OF SKELETAL METASTASIS ON BONE SCINTIGRAPHY IN PATIENTS WITH GERM CELL TUMOURS

Objective: Our aim was to determine the frequency of skeletal metastasis in germ cell tumours (GCT) at baseline and relapse on conventional technetium-99m methylene diphosphonate (Tc-99m MDP) whole body bone scan (bone scan) and to evaluate the effect of bone metastases on survival. Materials and Methods: Electronic medical records of histologically proven GCT over 64 months were retrospectively analysed. Basic demographic and histologic information were correlated with the presence of osseous and visceral metastases. 5-year disease-free survival (DFS) and overall survival (OS) were calculated in presence, the absence of bone metastases at baseline and at relapse. Results: A total of 130 gonadal and extragonadal GCT patients underwent Tc-99m MDP bone scans; four with insuf cient data were excluded from the study. 47% were females and 53% were males with the age range of 1 month – 72 years. 105 (83%) were under 18 years of age. Osseous metastasis was detected in 12 (9.5%). Two (17%) had solitary and 10 (83%) had multifocal skeletal metastases. Clinically, 83% had localised bone pain. Osseous metastases were more frequently associated with mixed GCT and yolk sac tumour. 50% of mediastinal GCT developed bone metastases. 42% died within 4–18 months. There was a statistically signi cant impact of visceral metastases on DFS and OS. OS at 5 years in patients without bone metastases, with bone metastases at baseline and bone metastases at relapse, was 77%, 38% and 75%, respectively. 5-year DFS for the same cohort groups was 63%, 38% and 20%, respectively. Conclusion: Osseous involvement was found in 9.5% of GCT patients undergoing diagnostic Tc-99m MDP bone scan. Baseline skeletal evaluation for metastases should be done, particularly in the case of bone pains or known systemic metastases. Although skeletal relapses are rare, they have a grim outcome. Key words: Bone scintigraphy, germ cell tumours, skeletal metastases

Submandibular Gland Epithelial-Myoepithelial Carcinoma with Osseous Metastasis: A First Reported Case and Review of the Literature

Epithelial-myoepithelial carcinoma (EMC) is a low grade tumor that comprises 1% of all salivary tumors. Local recurrence is not uncommon, but rarely does this tumor demonstrate distant metastasis. We describe a case of a 53-year old female presenting with an asymptomatic, slowly enlarging left submandibular neck mass. Excision of the left submandibular gland (SMG) revealed epithelial-myoepithelial carcinoma with extensive perineural invasion and microscopically positive margins. A subsequent left supraomohyoid neck dissection demonstrated no residual tumor. The patient was stable for one year until a magnetic resonance imaging (MRI) workup for low back pain revealed multiple sclerotic lesions in the iliac crest and lumbar spine, with an iliac crest biopsy demonstrating metastasis. 2.5 year post-operative positron emission tomography-computed tomography (PET-CT) revealed increased [18F]-fluorodeoxyglucose (FDG) avidity in the right iliac crest, pubic symphysis, thoracic and lumbar spine, 9th rib, and sternum concerning for local recurrence and further osseous metastasis. We report the first known case of a submandibular gland EMC with osseous metastasis and highlight the need for prolonged tumor surveillance.

The application value of Wb-dwi and Spect on diagnosing osseous metastases

Objective To investigate values of Wb-dwi on diagnosis of osseous metastases compared with Spect materials. Methods 20 cases with osseous metastases underwent Wb-dwi and Spect.The bones were divided into 6 groups: skull, collarbone, trunk bone, haunch bone, upper limb bone, lower limb bone.the high uptake regions on Spect and high signal on Wb-dwi for positive groups or positive lesions were recorded.Meanwhile, the total numbers of positive groups and positive lesions in different groups were also recorded.Finally, the diagnostic sensitivity and specificity of Wb-dwi and Spect were calculated, which was based on the total numbers of positive groups. Results Wb-dwi showed 69 positive groups, the numbers of positive lesions in each group were 2, 1, 85, 55, 22, 12.Spect showed 66 positive groups, the numbers of positive lesions in each group were 4, 3, 79, 47, 20, 18.The diagnostic sensitivity and specificity on Spect were 81.1%, 80.3%.The diagnostic sensitivity and specificity on Wb-dwi were 86.9%, 84.3%.No statistical difference was assessed between the sensitivity and specificity of two methods. Conclusion Compared with Spect, the Wb-dwi can show more osseous metastasis lesions and has higher sensitivity on diagnosis osseous metastases.In additional, it can demonstrate primary tumors and extraskeletal metastasis lesions. Key words: Magnetic resonance imaging, diffusion; Tomography, emission-computed, single-photon; Single-photon emission computed tomography

Radiation therapy for palliation of osseous metastasis from hepatocellular carcinoma.

204 Background: Osseous metastasis from hepatocellular carcinoma (HCC) is uncommon, and optimal palliative management for palliation is unclear. We present our clinical experience with palliative radiotherapy (RT) for osseous metastasis from HCC. Methods: Patients were identified using two prospectively maintained databases at our institution: all patients with HCC who developed metastases and all patients undergoing RT. Medical records were retrospectively reviewed following Institutional Review Board approval. We identified 146 patients with metastatic HCC, of which 28 patients with 38 osseous metastases were eligible for this analysis. All patients are seen in a multi-disciplinary clinic where consensus for management is developed. Most (89%) had metastasis at the time of initial tumor diagnosis, including 22 (79%) patients with osseous lesions at diagnosis. Tissue confirmation of metastasis was obtained in 22 (79%) patients. Outcomes of interest included patient-reported pain relief at time of follow-up, radiographic response at 6-12 months, and overall survival. Statistical analysis was performed with SPSS (IBM Corporation). Results: Median age at diagnosis was 61 years, and 86% (n = 24) were male. The most common site of metastasis was vertebral body (n = 26, 70%). Median time from bone metastasis diagnosis to RT was 1 month (range, 0-20). Only 1 patient received concomitant systemic therapy at the time of RT. Metastases were most commonly treated using 2D techniques (n = 26, 68%) to 30 Gy in 10 fractions (n = 18, 47%). Pain relief was complete, partial, and absent for 8 (21%), 24 (63%), and 6 (16%) metastases, respectively; no patient reported an increase in pain after treatment. Prescription BED3 > 50 Gy was associated with improved local control (P = .03). 7 (18%) radiographic local failures were observed at a median time of 5.4 months, and the 6-month local failure rate was 20.2%. Median survival was 3.4 months, with a 6-month survival rate of 39.1%. Conclusions: Mortality for patients with osseous metastasis from HCC is high, but palliative RT is associated with significant pain relief and/or disease control in many patients. This data on efficacy of palliative RT helps guide optimal management of these patients.

Safety and Tolerability of Extracranial Radiation Therapy and Immune Checkpoint Inhibitors Among Patients With Metastatic Non-Small Cell Lung Cancer

Immune checkpoint inhibitors (ICPIs) are revolutionizing systemic management of non-small cell lung cancer (NSCLC). There is limited published data on the use of radiation therapy (RT) before, during, or after administration of these agents. The goal of this study was to assess safety and tolerability among patients receiving extracranial external beam RT within 6 months before or after enrollment on prospective clinical studies of ICPIs for metastatic NSCLC. A total of 213 patients with Stage 4 NSCLC were enrolled in prospective ICPI trials at our institution. For all patients, ICPIs were delivered until disease progression. Of these patients, we identified 29 patients who received palliative RT between February 2012 and December 2015 to 39 unique osseous or intrathoracic sites within 6 months before or after enrollment on one of 9 prospective clinical studies evaluating safety and/or efficacy of either single agent ICPI (n = 7 anti-PD-1, n = 8 anti-PD-L1) or combined ICPIs (n = 5 anti-PD-1/CTLA-4, n = 9 anti-PD-L1/CTLA-4). RT associated toxicities were defined qualitatively based on review of the clinical chart. Kaplan-Meier (KM) estimates of progression-free survival (PFS) and overall survival (OS) were calculated from date of ICPI initiation. Among patients treated with RT, the median age at time of ICPI study enrollment was 64 years (range 47-75) with 15 males included (52%). The majority of patients had an ECOG 1 performance status (79%) with a median of 4 metastatic sites (range 2-9). Eight lesions (21%) were treated concurrently with systemic treatment. The median interval between ICPI and RT administration was 2.4 months (range 0.2-5.6 months) in lesions treated with RT before or after ICPI. Median PFS and OS were 3.6 months (2.6, not reached-95% CI) and 8.7 months (5.2, 10.8-95% CI), respectively with a median PFS/toxicity follow-up of 5.6 months (range: 0.5-39.7 months). Ten lesions (26%) were treated to thoracic sites and 29 lesions (74%) were treated to osseous sites. The most common osseous dose and fractionation schedules were 30 Gy in 10 fractions (52%) and 20 Gy in 5 fractions (34%) (range: 8-45 Gy in 1-15 fractions). Response to osseous palliative radiation could be qualitatively assessed in 26 lesions; symptomatic improvement either partial or full was noted in 20 lesions (77%). Thoracic RT doses ranged between 10 to 70 Gy in 1 to 35 fractions. One patient experienced possible RT related grade 5 pulmonary toxicity 2 weeks following completion of RT (4 Gy x 5 to right hilum/lung), which was initiated 1 month after last dose of anti-PD-1 therapy. There were no other unexpected RT associated toxicities. In this analysis of RT among NSCLC patients treated on prospective clinical studies with ICPIs, RT directed at osseous metastases was well tolerated. Among patients treated with thoracic RT, there was 1 possible grade 5 RT associated toxicity. ICPI and RT for intrathoracic disease should be further studied to better understand safety and tolerability.

Radiation Therapy for Palliation of Osseous Metastasis From Primary Liver Malignancy

Radiation Therapy for Palliation of Osseous Metastasis From Primary Liver Malignancy

The Diagnosis, Treatment, and Follow-up of Renal Cell Carcinoma.

In 2014, 15 500 persons in Germany were given the diagnosis of renal cell carcinoma. This disease is the third most common cancer of the urogenital system. The mean age at diagnosis is 68 years in men and 71 in men. Pertinent publications up to 2014 were retrieved by a systematic literature search and reviewed in a moderated, formalized consensus process. Key questions were generated and answered by the adaptation of existing international guidelines, on the basis of an independent literature review, and by expert consensus. Representatives of 30 medical specialty societies, patient self-help groups, and other organizations participated in the process. The search for guidelines yielded 80 hits, 23 of which were judged by DELBI to be potentially relevant; 7 were chosen for adaptation. Smoking, obesity, and hypertension increase the risk of renal cell carcinoma. Its 5-year survival rate is 75% for men and 77% for women. Renal cell carcinoma accounts for 2.6% of all deaths from cancer in men and 2.1% in women. Nephrectomy and partial nephrectomy are the standard treatments. Locally confined tumors in clinical stage T1 should be treated with kidney-preserving surgery. Minimally invasive surgery is often possible as long as the surgeon has the requisite experience. For patients with metastases, overall and progression-free survival can be prolonged with VEGF and mTOR inhibitors. The resection or irradiation of metastases can be a useful palliative treatment for patients with brain metastases or osseous metastases that are painful or increase the risk of fracture. Minimally invasive surgery and new systemic drugs have expanded the therapeutic options for patients with renal cell carcinoma. The search for new predictive and prognostic markers is now in progress.

Longitudinal analysis of bone metabolism using SPECT/CT and (99m)Tc-diphosphono-propanedicarboxylic acid: comparison of visual and quantitative analysis.

BackgroundThe therapy response of osseous metastases (OM) is commonly monitored by bone scintigraphies (BS). The aim of this study was to compare visual evaluation of changes in tracer uptake with quantitation in absolute units in OMs; 52 OMs from 19 patients who underwent BS with SPECT/CT at time points one and two (TP1/2) were analyzed retrospectively, with an average of 10.3 months between TP1 and 2. Tracer uptake in lesions was visually compared by two independent readers in both planar scintigraphies and SPECT/CT across both TPs and classified as regressive, stable, or progressive. Quantitative analysis was performed by measuring peak standardized uptake values (SUV). Based on quantitation, lesions were similarly classified as regressive (>30 % decrease), progressive (>30 % increase), or stable (rest). If available, uptake in reference regions in the lower thoracic or lumbar spine was used for normalization.ResultsIn OMs at TP1 and TP2, mean SUVpeak (±SD) was found to be 20.4 (±20.8) and 16.4 (±11.5), respectively. For the reference region, mean SUVmean was 5.6 (±1.9) and 4.9 (±2.2). Agreement between quantitative and visual assessment was only moderate, with an average Cohen’s kappa of 0.42 for planar scintigraphy and 0.62 for SPECT/CT. Discrepancies occurred in between 11 and 22 of the 52 lesions, depending on the reader and whether planar or SPECT imaging was considered.ConclusionsCompared to measuring uptake in absolute units, visual evaluation of skeletal scintigraphies for change in tumor metabolism yields inconsistent results in roughly one third of the cases.

Cirrhosis-related musculoskeletal disease: radiological review.

Musculoskeletal problems in patients with liver disease are common; however, they are not so well described in the literature. Therefore, there is a need to collate information on these disorders, as their incidence is on a constant rise and some of these pathologies can severely debilitate the patient's quality of life. These disorders are parietal wall varices with or without bleeding, spontaneous intramuscular haematoma (e.g. rectus sheath), abdominal wall hernia, anasarca, hepatic osteodystrophy, septic arthritis, osteomyelitis, necrotizing fasciitis, osseous metastases from hepatocellular carcinoma etc. While portal hypertension plays a key role in disorders, in others, dysregulation of the coagulation system or a compromised immune system are responsible. Imaging plays an essential role in the assessment of these complications and awareness of these musculoskeletal manifestations is vital for establishing a timely diagnosis and planning of appropriate therapy, as these disorders can significantly impact the morbidity and mortality and also influence candidacy for liver transplantation. We herein comprehensively appraise various musculoskeletal complications associated with chronic liver disease/liver cirrhosis especially from an imaging perspective which, to the best of our knowledge, have not been collectively described in English literature.

Supraclavicular Metastases from Distant Primary Solid Tumours: A Retrospective Study of 41Years.

Approximately 1% of all malignant solid tumours of the head and neck area are metastases from primary tumours beneath the clavicles. The aim of this study was to analyse the distribution of primary tumours since meta-analyses might have been biased due to the usually extraordinary character of case reports. All patient files from 1970 to 2012 from the Oral and Maxillofacial Surgery unit at a University Hospital were analysed regarding the existence of metastases to the head and neck area from distant primaries. Of the seventy-three patients 18 had breast cancers (25%), 9 melanomas (12%), 8 tumours of the kidneys and 8 of the lungs (each 12%), 3 colon cancers (6%), 2 prostate cancers (3%), 2 Ewing sarcomas (3%), and 1 each of liposarcoma, esophagus, rectum, hepatocellular carcinoma, vulva, ovarian and testicular cancer. In 15 cases, a cancer of unknown primary was diagnosed. In 28 cases the metastasis was the initial sign of the malignant disease. Skeletal metastasis occurred in 37 cases and a soft tissue metastasis in 36 patients. The different primaries seem to metastasize in different frequencies to the head and neck area. The relatively common prostate cancer rarely seems to produce metastases in the head and neck area compared to cancers arising in the kidneys. In case of a malignant tumour of unknown primary, osseous metastases most often are caused by breast or lung cancer or renal cell carcinoma. Soft tissue metastases are most often caused by breast cancer.