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Purpose: To investigate the value of multi-parametric MRI-based radiomics for preoperative prediction of lung metastases from soft tissue sarcoma (STS)., Methods: In total, 122 patients with clinicopathologically confirmed STS who underwent pretreatment T1-weighted contrast-enhanced (T1-CE) and T2-weighted fat-suppressed (T2FS) MRI scans were enrolled between Jul. 2017 and Mar. 2021. Radiomics signatures were established by calculating and selecting radiomics features from the two sequences. Clinical independent predictors were evaluated by statistical analysis. The radiomics nomogram was constructed from margin and radiomics features by multivariable logistic regression. Finally, the study used receiver operating characteristic (ROC) and calibration curves to evaluate performance of radiomics models. Decision curve analyses (DCA) were performed to evaluate clinical usefulness of the models., Results: The margin was considered as an independent predictor (p < 0.05). A total of 4 MRI features were selected and used to develop the radiomics signature. By incorporating the margin and radiomics signature, the developed nomogram showed the best prediction performance in the training (AUCs, margin vs. radiomics signature vs. nomogram, 0.609 vs. 0.909 vs. 0.910) and validation (AUCs, margin vs. radiomics signature vs. nomogram, 0.666 vs. 0.841 vs. 0.894) cohorts. DCA indicated potential usefulness of the nomogram model., Conclusions: This feasibility study evaluated predictive values of multi-parametric MRI for the prediction of lung metastasis, and proposed a nomogram model to potentially facilitate the individualized treatment decision-making for STSs., (© 2024. The Author(s).)

Background: Superficial soft tissue metastasis (S-STM) of malignant tumors is uncommon and often brings great pain to patients. However, current treatment options are limited. The purpose of this study was to explore the clinical efficacy and prognostic factors of CT-guided radioactive iodine-125 ( 125 I) seed implantation (RISI) for the treatment of S-STM., Methods: We retrospectively evaluated 132 patients with S-STM who received RISI between June 2010 and July 2022. Local tumor progression-free survival (ltPFS), tumor response, pain control and complication were analyzed. The independent factors affecting ltPFS were screened out using a layered Cox proportional hazards model., Results: The median follow-up time was 8.3 months (interquartile range [IQR], 4.5-15.3 months). The objective response rate (ORR) was 81.8%. The median ltPFS was 9.1 (95% CI: 6.6, 11.6) months. The Cox proportional hazard regression model revealed that the independent factors influencing ltPFS included KPS score, primary tumor, metastases, boundary, density and postoperative D90 (All P < 0.05). After RISI, the rate of pain relief was 92.3%. 66 (84.6%) patients reported pain marked relief, and 6 (7.7%) experienced pain moderate relief. No severe adverse events associated with RISI were observed during follow-up., Conclusions: CT-guided RISI was associated with high local control and pain relief without severe adverse events and should be considered as a reliable palliative treatment modality for S-STM., Trial Registration: Trial registration Retrospectively registered., (© 2024. The Author(s).)

Background: Soft-tissue metastasis of carcinoma is rare. In the present study, we investigated the surgical indications and clinical features of patients with soft tissue metastases of carcinoma., Methods: In this retrospective cohort study, we enrolled 26 patients with soft tissue carcinoma metastasis referred to our department for treatment. Sex, age, location, size, depth, pain due to the tumor, primary origin, serum C-reactive protein (CRP) level, MRI examinations, diagnosis by a previous physician, carcinoma markers from blood, history of carcinoma, other metastases, performance status (PS), and surgical procedures were documented. Associations between variables and surgery were statistically analyzed., Results: The primary cancer origin was found to be the lung (n = 10), kidney (n = 7), esophagus (n = 2), stomach (n = 1), breast (n = 1), liver (n = 1), ureter (n = 1), anus (n = 1), and unknown (n = 2). The mean CRP level of all patients was 2.3 mg/dL. Seven tumors (26.9%) were originally suspected to be soft tissue metastases of carcinoma, while 19 tumors (73.1%) were considered soft tissue sarcomas or inflammatory lesions by the previous treating physician. Twenty patients (76.9%) had other metastases. The PS of the 12 patients (46.2%) was zero. Eleven patients (42.3%) underwent surgery for soft tissue metastases. Diagnosis of soft tissue metastasis by a previous physician and good PS (p < 0.05) were significantly associated with surgery., Conclusion: Overall, the present results show that surgical indications for soft tissue metastasis of carcinoma include diagnosis by the referring physician or good PS of the patients., (© 2024. The Author(s).)

Purpose: In colorectal cancer (CRC) patients the selection of suitable cytoreductive surgery and hyperthermic peritoneal chemotherapy (CRS-HIPEC) candidates is based on the location and extent of peritoneal metastases (PM) and presence of extraperitoneal metastases. MRI is increasingly being used to accurately assess the extent of PM, however, the significance of extraperitoneal findings in these scans has never been evaluated before., Methods: CRC patients who had undergone an additional MRI scan after standard work-up with CT for preoperative staging between January 2016-January 2020 were selected. CT and MRI reports were reviewed for new abdominopelvic extra-peritoneal findings on MRI (MR-EPF) and MR-EPFs concerning lesions previously indicated as equivocal (uncertain benign/malignant) on CT. Reference standard were surgical results or follow-up imaging., Results: In 158 included patients 60 MR-EPFs (in 58/158 patients) were noted: twenty-six (43%) were new findings and thirty-four (57%) were equivocal findings on CT. Of the 34 equivocal findings 27 were 'rejected/less likely malignant' and 7 'confirmed/more likely malignant' based on MRI. In 29 patients (18%) the MR-EPFs had direct influence on treatment planning. Three patients (2%), eligible for CRS-HIPEC on CT, were deemed inoperable due to MR-EPFs., Conclusion: MRI had an added value in more than a third of the patients due to abdominopelvic extraperitoneal findings that were undetected or indeterminate on CT and therefore influenced the treatment in a substantial part of the patients. Combined with the known accurate detection of peritoneal disease on MRI, MRI seems a logical addition to the diagnostic workup of potential CRS-HIPEC candidates., Competing Interests: Declaration of competing interest None of the authors of this manuscript have any financial and personal relationships with other people or organizations that could inappropriately influence (bias) their work., (Copyright © 2021. Published by Elsevier Ltd.)

Objectives: Hemangiopericytomas (HPCs) and solitary fibrous tumors (SFTs) were considered two distinct entities, but a common gene fusion, NAB2-STAT6, has been identified in both. Although rare, HPCs and SFTs do metastasize, some many years later after resection. Given the extended disease-free interval, it can be difficult to determine with certainty if an HPC or SFT at a new anatomic location represents a second primary or metastatic disease., Methods: RNA was extracted from formalin-fixed, paraffin-embedded tissue of two patients with multiple SFT/HPC samples. The fusion gene was amplified by reverse transcription polymerase chain reaction (RT-PCR) and a custom-designed Archer FusionPlex panel (94 target genes) and the Illumina NextSeq 550., Results: We identified two patients with multiple resections for HPC/SFT during 26 years at our institution. The first patient had a history of HPC and almost 10 years later she was diagnosed with malignant SFT. The HPC and the SFT shared the same fusion breakpoint. The second patient had multiple lesions in the brain and bone/soft tissue over a 27-year span following a diagnosis of meningeal SFT. Three lesions from this patient shared the same fusion breakpoint., Conclusions: Our study demonstrated the same fusion breakpoints in primary and metastatic SFTs/HPCs at different time points using both RT-PCR and the Archer fusion panel., (© American Society for Clinical Pathology, 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Metastatic tumours of the hand are rare, and therefore, is the subject of only a few publications in the literature. We report on three new cases along with a retrospective and descriptive study with file and literature analysis dating from 1900 to 2017, which reported on 337 studies. To perform the statistical analysis, ordinary lease square regression was used to group the metastases into distal phalanx, proximal/middle phalanx, thumb, hand and carpus. We found 564 metastases at the hand for a total of 482 patients. Of the reported cases, 60% were male. The average age was 59 years. The main primary cancers were lung cancer (40%), followed by gastrointestinal (19%), genito-urinary (13%), gynaecological (11%) and ear, nose and throat (6%) cancers. The mean survival time was 7.2 months. Fifty-nine per cent was bone metastasis, 18% tissue metastasis and 3% cutaneous metastasis. In 20% of cases, the type of metastasis was not mentioned. Of all the tissue metastases, 47 (54%) were subungual and in that group, the thumb was the finger most commonly affected. Overall, metastases most commonly appeared in the distal phalanx, which can be explained by a greater vascularisation as well as microtraumatisms. Survival was independent of the epidemiological criteria and of the location and type of metastasis. Patients with primary urological cancer lived on average 3 months longer than patients with other types of primary cancers., Competing Interests: Declaration of Competing Interest The authors declare that they have nothing to disclose, (Copyright © 2021 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Abstract: Herpes zoster infection caused by reactivation of dormant varicella zoster virus results in painful vesicular rash in corresponding dermatome. We report a case of a 56-year-old woman with breast cancer who was referred to PET/CT scan for adjuvant chemotherapy response assessment. Her scan showed multiple FDG-avid skin lesions. Blinded to the patient's clinical information, these skin lesions initially looked suspicious for soft tissue metastases. However, the patient history revealed that she had been experiencing herpes zoster infection during the scan, and these lesions with FDG uptake were eventually confirmed to be caused by herpes zoster infection by physical examination., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Distant metastasis of retinoblastoma to sites outside the central nervous system is rare; such cases may present years following primary treatment. Diagnosis may be difficult given the rarity of such events and considerable histologic mimics. We describe the clinicopathologic features of 6 cases of metastatic retinoblastoma to distant bone and soft tissue sites from 2 large academic centers. Patients were 3 female and 3 male children; median age was 9.5 years (range: 5 to 15 y) with a mean interval from primary disease diagnosis of 8.0 years (range: 0.75 to 14 y). Metastasis to bones of the lower extremities was most common, occurring in 4 of 6 cases. Tumors showed typical histologic features of retinoblastoma, with sheets of primitive round cells with minimal cytoplasm and indistinct nucleoli; however, characteristic Flexner-Wintersteiner rosettes were absent. A subset of cases demonstrated an alveolar growth pattern, and 2 cases showed higher grade cytology with nuclear anaplasia and prominent nucleoli. Immunohistochemistry for CRX and RB1 showed uniform positivity and loss of expression, respectively. Metastatic retinoblastoma outside the central nervous system may present following long disease-free intervals. Immunohistochemistry for CRX is helpful to confirm this challenging diagnosis., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, blocks proliferation in a RB and cyclin D-dependent manner in preclinical prostate cancer models. We hypothesized that cotargeting androgen receptor and cell cycle with palbociclib would improve outcomes in patients with metastatic hormone-sensitive prostate cancer (mHSPC)., Patients and Methods: A total of 60 patients with RB-intact mHSPC were randomized (1:2) to Arm 1: androgen deprivation (AD) or Arm 2: AD + palbociclib. Primary endpoint was PSA response rate (RR) after 28 weeks of therapy. Secondary endpoints included safety, PSA, and clinical progression-free survival (PFS), as well as PSA and radiographic RR. Tumors underwent exome sequencing when available. Circulating tumor cells (CTC) were enumerated at various timepoints., Results: A total of 72 patients with mHSPC underwent metastatic disease biopsy and 64 had adequate tissue for RB assessment. A total of 62 of 64 (97%) retained RB expression. A total of 60 patients initiated therapy (Arm 1: 20; Arm 2: 40). Neutropenia was the most common grade 3/4 adverse event in Arm 2. Eighty percent of patients (Arm 1: 16/20, Arm 2: 32/40; P = 0.87) met primary PSA endpoint ≤4 ng/mL at 28 weeks. PSA undetectable rate at 28 weeks was 50% and 43% in Arms 1 and 2, respectively ( P = 0.5). Radiographic RR was 89% in both arms. Twelve-month biochemical PFS was 69% and 74% in Arms 1 and 2, respectively ( P = 0.72). TP53 and PIK3 pathway mutations, 8q gains, and pretreatment CTCs were associated with reduced PSA PFS., Conclusions: Palbociclib did not impact outcome in RB-intact mHSPC. Pretreatment CTC, TP53 and PIK3 pathway mutations, and 8q gain were associated with poor outcome., (©2021 American Association for Cancer Research.)

Objective: Soft tissue metastases (STM) in head and neck cutaneous squamous cell carcinoma (HNcSCC) are non-nodal based metastases to the parotid and cervical soft tissues of the head and neck. This is a unique subgroup of regional metastases amongst patients with cSCC and have been shown to be associated with poor prognosis. Detailed studies of this subgroup are lacking in the literature. A retrospective cohort analysis was performed to characterize the prognostic significance of STM in HNcSCC based on individual clinicopathological features., Methods: Patients with HNcSCC with STM were identified from the Sydney Head and Neck Cancer Institute database. Clinicopathological characteristics were extracted from the histopathological reports. Recurrence and follow-up data were analyzed to determine disease-free and overall survival using the Kaplan-Meier method and Cox proportional hazards models., Results: After excluding all patients with lymph node metastasis with no STM, there were 200 patients identified (161 parotid, 32 cervical, and seven with concurrent parotid and cervical STM) with a 5-year overall survival of 36%. In univariable analysis, age of patients, size of the deposits, location of the deposits, and patients that were not offered adjuvant radiotherapy have worse overall survival. However, on multivariable analysis, age and the number of STM deposits were independent factors that predict for worse survival., Conclusion: The presence of STM in patients with HNcSCC is associated with poor prognosis. Increasing number of STM deposits, as well as involved margin of the regional excision, negatively impacted on the overall prognosis., Level of Evidence: Level III - retrospective cohort study. Laryngoscope, 131:E1209-E1213, 2021., (© 2020 American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA).)

Orthopedic surgeons are well aware of tumor contamination at the site of initial biopsy in osteosarcoma. However, tumor contamination in patients with osteosarcoma associated with thoracic instrumentation is not well described. The authors summarize 2 reported cases in addition to the 2 cases at their institution of this phenomenon. Knowledge of tumor contamination and preventative measures against tumor contamination is sparse in the literature, especially pertaining to patients with osteosarcoma undergoing thoracic instrumentation. In this report, the authors hope to increase awareness of these cases and suggest preventative measures to mitigate against tumor contamination in patients with osteosarcoma. The authors report that the median time between thoracic instrumentation and the visible detection of tumor migration to local sites was 5 months. They conclude that tumor contamination associated with thoracic instrumentation is characterized by patients with multiple sites of relapse and aggressive, fatal disease., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study aimed to investigate the clinical, pathological, and prognostic characteristics of acral metastases in patients with malignant disease and to determine the impact of different types of acral metastasis treatment on patient survival., Methods: In this retrospective study, 64 acral metastatic lesions in 46 patients (17 women, 29 men; mean age, 61.5 years; age range, 35-82 years) who were evaluated by the Bone and Soft Tissue Tumors Council of our institute from 2015 to 2019 were included. The patients' primary tumor site, tumor type, localization of acral metastases, main symptom, duration from the diagnosis of the primary tumor to the diagnosis of acral metastasis, duration from the diagnosis of acral metastasis to death, and survival data were analyzed. The diagnosis of acral metastasis was confirmed by histopathological evaluation in 38 patients and clinical and radiological assessment of the lesions in 8 patients. The treatment type for each acral metastasis was individualized by the institutional Bone and Soft Tissue Tumors Council and categorized into 3 groups: excisional surgery (amputations and resections), palliative surgery (prophylactic fixation, intralesional curettage, and bone cement augmentation), and non-surgical treatment (chemotherapy, radiotherapy, and hormone therapy)., Results: A total of 16 acral metastases (25%) were identified in the upper extremity and 48 (75%) in the lower extremity. The most common primary tumor site was the lungs (32.6%), and the most common tumor type was adenocarcinoma (43.2%). The most frequent symptom and the primary reason for admission was pain (58.7%). The mean duration between the diagnosis of primary tumor and the diagnosis of acral metastasis was 19.1 (range, 0-124) months. No significant correlation was determined between the primary tumor types and duration from the diagnosis of primary tumor to the diagnosis of acral metastasis (p=0.278). Acral metastases were treated by excisional surgery in 15 (32.6%) patients, palliative surgery combined with non-surgical treatment in 10 (21.7%) patients, and only non-surgical treatment modalities in 21 (45.7%) patients. No significant correlation existed between the treatment types and patient survival (p=0.058). At the final follow-up, 30 (65.2%) patients were dead owing to the disease. The mean overall survival of the entire study group was 24.9 (range, 3-55) months. The mean duration between the diagnosis of acral metastasis and death was 7.6 (range, 3-24) months in patients who were dead owing to the disease (p=0.012)., Conclusion: When the diagnosis of acral metastasis is established, it should be borne in mind that the most common primary tumor site and type are most likely the lungs and adenocarcinoma, respectively. The treatment type for acral metastasis may have no significant impact on patient survival, but the extensiveness of the disease may be a critical factor for survival., Level of Evidence: Level IV, Prognostic study.

Composite sarcoma of bone is a very rare entity that primarily affects adolescent and young adult patients. It usually combines areas of liposarcoma and osteosarcoma, and up to 60% of cases have metastatic disease at diagnosis. It is a highly aggressive pathology with intrinsic resistance to bone sarcoma conventional treatments. The prognosis is poor, with long-term survival rates not exceeding 30%. We present the case of an adolescent female diagnosed with an aggressive composite sarcoma of bone with rhabdomyosarcoma foci and loco-regional lymph node involvement., (© 2020 Wiley Periodicals LLC.)

Metastatic tumours of the distal extremities, also known as acrometastases, are rare. The majority of the acrometastases involve bones-involvement of the soft tissues of the feet and hands is extremely rare. We report a case of clear cell renal cell carcinoma metastasised to the soft tissues of the foot. The patient presented with pain and swelling in his right foot. Diagnosis of acrometastases frequently gets delayed due to the rarity of this condition and resultant low clinical suspicion. Possibility of metastatic disease should be entertained as an important differential diagnosis when patients with a history of cancer present with musculoskeletal symptoms. A systematic evaluation incorporating thorough clinical assessment, advanced imaging techniques like MRI and pathological examination is critical to establish the diagnosis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/objectives: Oligometastatic sarcoma pulmonary metastases (PM's) are traditionally treated with resection and/or chemotherapy. We hypothesize that stereotactic body radiotherapy (SBRT) is an effective, safe alternative to surgery that can achieve excellent local control (LC) with a favorable toxicity profile., Methods: Patients treated with SBRT for sarcoma PM's from 2011 to 2016 at Massachusetts General Hospital and the University of Pennsylvania were included. Median dose was 50 Gy. Patients underwent computed tomography (CT) or positron emission tomography/CT Q3 months post-SBRT., Results: 44 patients with 56 separate PM's were treated with SBRT. Median age was 59 (range 19-82). 82% received prior chemotherapy, 66% had prior pulmonary resections (range, 1-5 resections), and 32% received prior thoracic radiotherapy. Median lesion size was 2.0 cm (range, 0.5-8.1 cm). Median follow-up was 16 months and 25 months for patients alive at last follow-up. Overall survival at 12 and 24 months was 74% (95% confidence interval [CI], 67%-81%) and 46% (95% CI, 38%-55%). LC at 12 and 24 months was 96% (95% CI, 93%-98%) and 90% (95% CI, 84%-96%). LC and overall survival did not differ based on age, gender, histology, fractionation, lesion location, or size (P > .05). Three developed Common Terminology Criteria for Adverse Events version 4 grade-2 chest-wall toxicities; one had grade-2 pneumonitis., Conclusions: In the first multi-institutional series on SBRT for sarcoma PM's, SBRT has excellent LC and is well-tolerated. SBRT should be considered as an alternative/complement to resection., (© 2020 Wiley Periodicals LLC.)

Introduction: It is well known that malignant cells can be implanted at distant donor sites due to iatrogenic surgical contamination. Only a small number of reports, however, have been published describing this., Case Presentation: We present a case of oral cavity Squamous Cell Carcinoma (SCC) reconstructed with a radial forearm free flap in which SCC developed in the subcutaneous tissues beneath the donor incision site 6 months after surgery., Management: The implanted tumor was excised and the field was subsequently treated with radiation. The patient remains disease-free on follow-up., Discussion: We present the second report of tumor implanted in a free flap donor site. Additionally, we discuss the risks of tumor implantation, review the literature, and make recommendations to avoid this complication.

Purpose: To describe ablation of bone, liver, lung, and soft tissue tumors from oligometastatic breast cancer and to define predictors of local progression and progression-free survival (PFS)., Materials and Methods: A total of 33 women (mean age 52 ± 12 years old; range, 28-69 years), underwent 46 thermal ablations of liver (n = 35), lung (n = 7), and bone/soft tissue (n = 4) metastases. Mean tumor diameter was 18 ± 15 mm (range, 6-50 mm). Ablations were performed to eradicate all evident sites of disease (n = 24) or to control growing sites in the setting of other stable or responding sites of disease (n = 22). Patient characteristics, ablation margins, imaging responses, and cases of PFS were assessed. Follow-up imaging was performed using contrast-enhanced computed tomography (CT), magnetic resonance (MR) imaging, or positron-emission tomography/ CT., Results: Median PFS was 10 months (95% confidence interval [CI], 6.2 -14.5 months), and time to local progression was 11 months (95% CI, 5-16 months). Eight patients (24%) maintained no evidence of disease during a median follow-up period of 39 months. Ablation margin ≥5 mm was associated with no local tumor progression. Longer PFS was noted in estrogen receptor-positive patients (12 vs 4 months; P = .037) and younger patients (12 vs 4 months; P = .039) treated to eradicate all sites of disease (13 vs 5 months; P = .05). Eighteen patients (55%) developed new metastases during study follow-up., Conclusions: Thermal ablation of oligometastatic pulmonary, hepatic, bone, and soft tissue tumors can eliminate local tumor progression if margins are ≥5 mm. Longer PFS was observed in patients who were estrogen receptor-positive and patients who were younger and in whom all sites of disease were eradicated., (Copyright © 2020 SIR. Published by Elsevier Inc. All rights reserved.)

Background: The use of radiation therapy to treat metastases in patients with metastatic Ewing sarcoma (MES) has been controversial and variable. The authors report outcomes and patterns of failure after metastatic site irradiation (MSI)., Procedure: A total of 27 pediatric patients with MES were treated with chemotherapy and received radiation therapy to their primary site. Ten patients additionally received MSI, which consisted of whole-lung irradiation (WLI) in patients with lung metastases. Metastatic sites were followed from diagnosis to the first relapse., Results: Median follow-up was 29 months. Seventy-eight percent of patients relapsed. Two-year progression-free survival (PFS) and overall survival with and without MSI were 30 versus 29% (log rank P=0.38) and 60 versus 70% (log rank P=0.11), respectively. The median time to relapse among patients who relapsed was 19.5 versus 12.3 months for those receiving MSI versus those who did not (P=0.04).Seven of 20 (35%) patients with lung metastases received WLI±other MSI. Two-year PFS with and without MSI was 43% versus 23% (log rank P=0.02). Among patients with a complete response to computed tomography, 5 of 14 (36%) patients received MSI. Two-year PFS with and without MSI was 60% versus 33% (log rank P=0.04).In the cohort of patients who relapsed, among all metastatic sites at diagnosis, the disease recurred at 15% of irradiated sites and 31% of unirradiated sites. On logistic regression, no factors were statistically associated with increased risk of recurrence at initial sites of metastases., Conclusions: Relapses frequently occur at sites of prior unirradiated disease in patients with MES. WLI may improve 2-year PFS, regardless of chemotherapy response. Further investigation of the role of MSI is warranted.

Background: Soft-tissue metastasis (STM) is a relatively rare, but not exceptional, manifestation of lung cancer. The purpose of this study was to evaluate the imaging features of STM from lung cancer using fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT), and assess the impact of STM detected at baseline PET/CT on patient survival., Methods: Out of 4543 patients with lung cancer who underwent 18 F-FDG PET/CT in our hospital between January 2013 and September 2018, 85 were diagnosed with STM (78 at baseline PET/CT and 7 at restaging PET/CT) and included in the imaging study. We conducted a comparative survival analysis between patients with stage 4 lung cancer with and without STM at baseline PET/CT (n = 78 in each group) and performed univariate and multivariate analyses to investigate the factors affecting the prognosis of lung cancer., Results: A total of 219 lesions were identified by 18 F-FDG PET/CT: 215 were detected by PET and 139 by CT. Muscle STM were primarily found in the hip and upper limb muscle, whereas subcutaneous STM were mainly distributed in the chest, abdomen, and back. In 68 patients, STM were found incidentally during routine 18 F-FDG PET/CT staging. Isolated STM were detected in 6 patients, whose tumor staging and treatment were affected by PET/CT findings. There were no significant differences in the 1-, 3-, and 5-year survival rates between patients with and without STM at baseline PET/CT. Brain and adrenal metastases, but not STM, were associated with poor prognosis of stage 4 lung cancer., Conclusions: We described the PET/CT imaging characteristics of STM from lung cancer, and confirmed that PET/CT can detect unsuspected STM to change the staging and treatment of some patients. Our analysis indicates that STM is not a useful prognostic indicator for patients with advanced lung cancer, while brain and adrenal metastases portend a poor prognosis.

Neuroblastoma is the most common extracranial solid tumor, arising from primitive sympathetic ganglion cells, in pediatric patients. The unique features of neuroblastoma include variable clinical behaviors, such as rapid progression to death and maturation to benign ganglioneuroma, followed by regression. Radiation therapy (RT) is usually administered to both the primary tumor bed and persistent metastatic sites after induction chemotherapy for high-risk neuroblastoma. RT to the tumor bed after surgical resection contributes significantly to local disease control and prevention of local relapse, confirming the role of RT. Palliative radiotherapy for metastatic neuroblastoma is also effective and safe and mainly provides symptomatic relief. The late side effects of RT in neuroblastoma patients include growth and developmental failure, hypothyroidism, gastrointestinal dysfunction, neurocognitive defects, pulmonary and cardiac abnormalities, infertility, and secondary cancers. In this article, we reviewed the role and toxicity of RT in neuroblastoma patients., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest in this work., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ossifying fibromyxoid tumors (OFMTs) are rare tumors of uncertain origin and intermediate (rarely metastasizing) biologic potential, with characteristic morphology of an encapsulated tumor containing polygonal cells in an abundant fibromyxoid matrix surrounded by a peripheral layer of metaplastic lamellar bone. FNA cytology of OFMT has not been sufficiently reported and till date cytological features of only seven cases have been reported so far. We report another case of OFMT in a 55-year-old female presenting with longstanding swelling in thigh. On fine-needle aspiration, a tumor with moderate cellularity and myxoid areas was seen; coupled with compatible radiological findings, a diagnosis of OFMT was suggested. Establishing a correct diagnosis is important as although OFMT is benign in nature, local recurrences or rarely distant metastasis have been seen of this tumor. Hence, a high degree of suspicion with radiological correlation is of utmost importance for identification of this entity., (© 2020 Wiley Periodicals, Inc.)

Background: Bone infiltration of the tumour is common in meningioma surgery. This may also affect patients without indicative signs of bone infiltration on preoperative imaging. Unrecognized bone invasion may lead to higher recurrence rates. 5-ALA fluorescence-guided resection (5-ALA-fg) could be a promising tool to help recognize possible bone invasion and/or tumour remnants. However, there is still little data about 5-ALA-fg resection in bone and soft tissue infiltrating meningiomas., Methods: We performed a retrospective study of 11 patients who were operated with the aid of 5-ALA due to bone and soft tissue infiltrating meningiomas at the University Hospital of St. Poelten between 2013 and 2019., Results: Strong and homogeneous fluorescence of the meningioma was observed in 9 cases (81.8%) and vague and heterogeneous fluorescence in 2 cases (18.2%). Hyperostosis on computerized tomography was evident in 3 of 6 cases (50%) and bone infiltration was visible in preoperative magnetic resonance imaging in 7 of 11 patients (63.6%). All eleven patients showed positive fluorescence of the bone infiltrating part. In all 7 cases where tissue could be collected, histopathological testing verified tumour infiltration (100%). There was also fluorescence of the periosteum in 3 cases and histopathological testing verified tumour infiltration in 100%., Conclusion: There is growing evidence that 5-ALA-fg resection can help to identify bone infiltration in meningioma surgery. Therefore, it may help to improve extent of resection. However, further studies are necessary to investigate the rate of false-negative fluorescence and its effect on progression free survival. If 5-ALA-fg resection of meningioma is performed, the attending surgeon should also consider investigating the adjacent periosteum under blue light for detection of possible fluorescence.

Background: Synchronous renal cell carcinoma metastasizing to the pancreas and subcutaneous tissue is very rare. Unusual metastatic sites require attention during follow-up of renal cell carcinoma. It is extremely rare for renal cell carcinoma to metastasize to the pancreas; it is also very rare for it to metastasize to the subcutaneous tissue and extremely rare for it to synchronously metastasize to the pancreas and subcutaneous tissue almost a decade after radical nephrectomy. It is well known that most pancreatic tumors are primary pancreatic adenocarcinoma. However, the pancreas can also be an uncommon site for metastasis. We present a rare case of synchronous metastasis of renal cell carcinoma to the pancreas and subcutaneous tissue; we believe it to be only the second such case reported to date., Case Presentation: We describe a case of a 74-year-old Chinese man who was diagnosed with metastatic renal cell carcinoma to the pancreas and subcutaneous tissue at the same time, 10 years after left radical nephrectomy. He received distal pancreatectomy with spleen preservation plus resection of the subcutaneous tissue lesions on the left side of the anterior abdominal wall and right waist. Pathology showed that all resected metastatic tumors were of the clear cell type. The patient was seen in regular follow-up afterward., Conclusion: Synchronous metastatic renal cell carcinoma to the pancreas and subcutaneous tissue is very rare, and it might occur after primary tumor resection. Patients must undergo lifelong monitoring and follow-up with regular examination so that any possible metastasis can be detected early. The optimal resection strategy should involve adequate resection margins and maximal tissue preservation of the pancreas, because renal cell carcinoma metastasizing to the pancreas and subcutaneous tissue has a good prognosis with long-term survival.

68Ga-PSMA-11, the radiotracer of choice for imaging of prostate cancer (PCa), may be produced with several radiolabeling techniques. Current study aimed to analyze various imaging parameters of the cold kit methodology produced 68Ga-PSMA-11 (68Ga-isoPROtrace-11) and to compare the results to available data in literature. Eighty 68Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) scans were evaluated. 68Ga-isoPROtrace-11 for all the studies was produced by the room temperature cold kit methodology using a lyophilized ready-to-use vial. Normal biodistribution of the tracer was recorded by measuring mean standardized uptake value (SUVmean) and compared to the available published data. Pathological tracer uptake was measured using SUVmax in prostate gland (48 patients), lymph nodes (22 patients), bones (20 patients) and soft tissues (6 patients). Average tumour-to-background and tumour-to-liver contrast ratios were calculated. The data of 80 68Ga-PSMA-11 PET/CT scans were analyzed. Radiochemical purity of the tracer was 91% or more. The highest normal tissue uptake value of 68Ga-isoPROtrace-11 was found in the kidneys (average SUVmean 41.7), followed by the parotid (average SUVmean 14.5) and submandibular glands (average SUVmean 13.02). Normal prostate tissue showed low tracer uptake (average SUVmean 2.4). The biodistribution of 68Ga-isoPROtrace-11 in normal tissues was found to be similar to other published results. Pathological uptake (average SUVmax ± standard deviation) in prostate gland was 11.3 ± 7.5, in lymph node metastases 14.6 ± 13.7, in bones 15.9 ± 15.9 and 24.2 ± 16.4 in soft tissues. Average tumour uptake of 68Ga-isoPROtrace-11 in prostate was 11.3, in lymph node metastases 14.6, in bone metastases 15.9 and in soft tissue metastases 24.2. Average tumour-to-liver and tumour-to-mediastinal blood pool ratios were 2.7 and 13.54 respectively. This study presents biodistribution data of 68Ga-isoPROtrace-11 in a large PCa patient subset, showing clinical applicability of the tracer. Using cold kit technology may enable a high quality and easy labeling process.

Objectives: There is no study published regarding the benefit of radiation therapy (RT) in combination with immune checkpoint inhibitors (ICIs) for the treatment of metastatic renal cell cancer (mRCC). This report is part of an exploratory study aiming to determine the immunomodulatory activity of RT alone or in combination with pembrolizumab in solid tumors., Materials and Methods: mRCC patients were treated with a combination of RT (8 Gy×1 or 4 Gy×5) followed by pembrolizumab with or without lead-in dose of pembrolizumab. Treatment response was measured based on the modified Response Evaluation Criteria in Solid Tumors criteria. Adverse events were monitored and graded. Pre-RT and post-RT tumor biopsies were obtained to evaluate programmed death-ligand 1 expression. Immune markers from peripheral blood before, during, and after treatment were analyzed using flow cytometry., Results: Twelve mRCC patients who progressed on prior antiangiogenic therapy were enrolled. Half had 2 lines of prior therapy. Two patients (16.7%) had partial responses and were on study for 12.4 and 14.5 months. Three patients had stable disease for a period ranging from 4.2 to 10.4 months, whereas 7 patients had progressive disease. Median progression-free survival was 8.6 months and median overall survival was 32.3 months. Three patients had grade ≥3 events (hyperglycemia, thrombocytopenia, transaminitis). Biopsied tissue programmed death-ligand 1 expression and tumor-infiltrating lymphocytes were numerically higher in responders comparing to nonresponders (Modified Proportion Score 45% vs. 30.45%; tumor-infiltrating lymphocytes odds ratio 4.92)., Conclusion: Combining RT with pembrolizumab in pretreated mRCC is well-tolerated and appears to have comparable efficacy with single-agent nivolumab.

A 69 y/o woman with a history of primary diffuse large B cell lymphoma in the right thigh muscle was referred for recurrence evaluation with 18F-FDG PET/CT. After routine courses of chemoradiation, MRI was done in order to evaluate treatment response with inconclusive findings. 18FDG PET/CT revealed abnormal uptake in the primary site of the disease as well as secondary involvement of stomach, pancreas, pelvic lymph nodes, and both tibiae. Our case showed the importance of 18F-FDG PET/CT in the detection of unusual soft tissue extension of lymphoma.

Objectives: Soft tissue metastasis (STM) is an uncommon condition in carcinoma. Although various case series related to STM have been reported, few reports have examined prognostic factors. This study aimed to evaluate the characteristics of STM and the factors affecting its prognosis., Materials and Methods: Patients with STM from carcinoma were retrospectively studied. The patients' information, including age, sex, primary tumor, metastasis location, size of the metastatic tumor, presence of pain, histological classification, history of primary tumor treatment, and other metastasis at diagnosis of STM were collected and associated with prognosis., Results: Overall, 16 patients with a mean age of 68.7 years were evaluated. The overall survival rate was not significantly different between lung cancer and non-lung cancer patients. The overall survival rate was significantly better in patients undergoing definitive treatment for the primary tumor than in those without history of treatment (p = 0.046). The overall survival rate of STM patients with no metastasis was significantly better than those with other metastasis at the diagnosis of STM (p = 0.041). On multivariate analysis, no history of primary tumor treatment and STM without pain were risk factors for prognosis (p = 0.0340 and 0.0474, respectively). None of the patients who developed STM under the skin experienced pain, while 92.3% of the patients who developed STM in the deep layer had pain., Conclusion: The risk factors for poor diagnosis of STM were no past treatment of the primary tumor and absence of pain. STM in the deep layer is prone to pain., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Introduction: Myxoid Round cell containing myxoid liposarcomas (MRCLS) have a high propensity to metastasize to soft tissue and bone. Whole Body Magnetic Resonance Imaging (BMRI) has been reported as a critical modality to early detect disease spreading in asymptomatic patients. The purpose of this study is to describe metastatic patterns and outcomes in patients through annual BMRI surveillance after diagnosis of MRCLS of the extremities and trunk., Materiel and Patients: This retrospective study included patients with histology confirmed MRCLS. Initial BMRI were done within 6 months following the first line treatment then once a year., Results: Forty-five out of 51 consecutive MRCLS patients were included. At the last follow-up 10 patients (22.2%) had an extra-pulmonary soft-tissue or/and bone metastasis detected in a median delay of 22.7±16 months [0-49] from the diagnosis of the MRCLS. Nine patients were asymptomatic. Finally, 5-years metastatic free survival was 72±8%. All metastatic patients had multiple lesion within the year following the first lesion diagnosis., Conclusion: Systematic BMRI in MRCLS patients following treatment frequently identify extra-pulmonary metastasis in asymptomatic patients within the first 5 years of follow-up. Despite a long survival can be expected after diagnosis, extra-skeletal metastasis was a signal of disseminated disease., (Copyright © 2019. Published by Elsevier Ltd.)

Rationale: The prognosis of lung cancer is dismal, which has resulted in lung carcinoma being one of the leading causes of cancer-related deaths worldwide. Non-small cell lung cancer accounts for approximately 80% of all types of lung carcinoma. The skeletal system and central nervous system are the most common distal metastatic sites in patients with lung cancer, while cutaneous and soft tissues metastasis is rare., Patient Concerns: We report a case of concomitant metastasis in the nasal tip and suspected buttocks metastasis secondary to lung cancer, who complained of repeated cough and white sputum for 6 months., Diagnose: Primary lung cancer was diagnosed by bronchoscopy and biopsy, lesion on nasal tip was confirmed by biopsy. Furthermore, PET-CT scan identified the untouchable buttocks lesion that could have been easily missed., Interventions: This patient refused systemic treatments, but he chose traditional Chinese medicine at home., Outcomes: He died 6 months after the diagnosis., Lessons: The possibility of metastasis of primary cancers should be considered when encountering soft-tissue neoplasm lesions, and a biopsy of the suspicious cutaneous lesions could likely aid in the histological identification of the primary cancer. PET-CT scan could be an effective supplementary tool for the diagnosis and evaluation of cancers.

Metastatic castration-resistant prostate cancer (mCRPC) has a highly complex genomic landscape. With the recent development of novel treatments, accurate stratification strategies are needed. Here we present the whole-genome sequencing (WGS) analysis of fresh-frozen metastatic biopsies from 197 mCRPC patients. Using unsupervised clustering based on genomic features, we define eight distinct genomic clusters. We observe potentially clinically relevant genotypes, including microsatellite instability (MSI), homologous recombination deficiency (HRD) enriched with genomic deletions and BRCA2 aberrations, a tandem duplication genotype associated with CDK12 -/- and a chromothripsis-enriched subgroup. Our data suggests that stratification on WGS characteristics may improve identification of MSI, CDK12 -/- and HRD patients. From WGS and ChIP-seq data, we show the potential relevance of recurrent alterations in non-coding regions identified with WGS and highlight the central role of AR signaling in tumor progression. These data underline the potential value of using WGS to accurately stratify mCRPC patients into clinically actionable subgroups.

Objective: The aim of this retrospective study is to analyze and classify magnetic resonance imaging (MRI) features of primary myxofibrosarcoma (MFS) of the extremities and their correlation with patients' prognosis (local recurrence [LR] and sarcoma-specific survival [OS])., Methods: Ninety-four patients with primary MFS of the extremities were included. All MRI were performed with 1.5 Tesla magnet using a standard protocol. The presence of a "tail pattern" was recorded. Myxoid tumor component and contrast enhancement of the tumor were evaluated and graded with semiquantitative method using a newly proposed classification., Results: A tail-like pattern was observed in 32% MFS; most of the tumors presented with high myxoid features and high grade of gadolinium (Gd) enhancement. Type 3 myxoid characteristics (P = 0.003) were most often observed in FNCLCC grade 3 tumors. Estimated LR-free survival rate was 70.3% at 3 and 58.4% at 5 years. A higher LR-rate was observed in those tumors presenting a tail-like pattern at MRI (P = 0.039), in those with myxoid features type 2 and 3 (0.047) and in those with Gd enhancement grade 2 or 3 (P = 0.029). A worse OS was observed in Gd enhancement grade 3 (P = 0.013) and in deep tumors (P = 0.031)., Conclusions: MFS features on preoperative MRI can be useful in order to identify risk classes of LR and OS. These data may suggest that patients with a tail-like pattern, high Gd enhancement and high myxoid features should be followed up more carefully after surgery., (© 2019 John Wiley & Sons Australia, Ltd.)

Background: Metastatic carcinoma to skeletal muscle and/or subcutaneous fat is a rare event. Only 27 cases of esophageal cancer to soft tissue have been described in the English-language literature., Purpose: Our goal was to describe the prevalence and clinical characteristics of soft-tissue metastasis among patients with primary esophageal cancer at a single institution., Methods: We performed a retrospective review of all patients with primary esophageal cancer. Data points analyzed included histologic subtype, anatomic location, metastasis pattern, treatment, and survival. Kaplan-Meier curves were used to estimate survival time, and log-rank tests were used for comparisons. For all analyses, P < 0.05 was considered significant., Results: Of 1341 patients with primary esophageal cancer, 25 (1.9%) had metastases to soft tissue. Soft-tissue metastases were diagnosed at a median age of 64 years, a median 9.6 months after esophageal cancer diagnosis. Adenocarcinoma was the predominant histopathological type, and soft-tissue metastasis was most common in the lower extremity. Local intervention was used for 10 symptomatic patients with favorable prognoses. Chemotherapy was the only treatment modality in 18 patients. Median survival time after diagnosis of soft-tissue metastasis was 8.9 months and was longer in patients with metastasis in soft tissue only (24.6 months, P = 0.007) and in those who received local intervention (11.1 months vs those who did not, P = 0.020)., Conclusion: We estimate the prevalence of soft-tissue metastasis to be 1.9% among patients with esophageal cancer. Local intervention may be beneficial for patients in otherwise good health with symptomatic soft-tissue lesions.

A 68-year-old man underwent ultrasound-guided needle biopsy of a suspicious renal mass. Just two weeks later, a large number of subcutaneous nodules was found in patient's chest-back, neck and axilla. pathology analysis was found to be metastatic subcutaneous nodules, These features suggest that tumor seeding have occurred during the needle biopsy. Despite needle tract seeding is a rare event, this rare complication should be taken into consideration before contemplating its use in a patient.

Background: Randomised trials comparing the efficacy of standard endocrine therapy (ET) versus experimental ET + bevacizumab (Bev) in 1st line hormone receptor-positive patients with metastatic breast cancer have thus far shown conflicting results., Patients and Methods: We pooled data from two similar phase III randomised trials of ET ± Bev (LEA and Cancer and Leukemia Group B 40503) to increase precision in estimating treatment effect. Primary end-point was progression-free survival (PFS). Secondary end-points were overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR) and safety. Exploratory analyses were performed within subgroups defined by patients with recurrent disease, de novo disease, prior endocrine sensitivity or resistance and reported grades III-IV hypertension and proteinuria., Results: The pooled sample consisted of 749 patients randomised to ET or ET + Bev. Median PFS was 14.3 months for ET versus 19 months for ET + Bev (unadjusted hazard ratio [HR] 0.77; 95% confidence interval [CI] 0.66-0.91; p < 0.01). ORR and CBR with ET and ET + Bev were 40 versus 61% (p < 0.01) and 64 versus 77% (p < 0.01), respectively. There was no difference in OS (HR 0.96; 95% CI 0.77-1.18; p = 0.68). PFS was superior for ET + Bev for endocrine-sensitive patients (HR 0.68; 95% CI 0.53-0.89; p = 0.004). Grade III-IV hypertension (2.2 versus 20.1%), proteinuria (0 versus 9.3%), cardiovascular (0.5 versus 4.2%) and liver events (0 versus 2.9%) were significantly higher for ET + Bev (all p < 0.01). Hypertension and proteinuria were not predictors of efficacy (interaction test p = 0.33)., Conclusion: The addition of Bev to ET increased PFS overall and in endocrine-sensitive patients but not OS at the expense of significant additional toxicity., Trials Registration: ClinicalTrial.Gov NCT00545077 and NCT00601900., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

OBJECTIVE. The purpose of this study was to determine the diagnostic accuracy of 68 Ga-labeled prostate-specific membrane antigen 11 (PSMA-11) PET for disease detection in patients with prostate cancer who have biochemically recurrent disease after radiation therapy or prostatectomy. SUBJECTS AND METHODS. One hundred fifty patients underwent 68 Ga-PSMA-11 PET/CT or PET/MRI, and the images were interpreted by two blinded board-certified radiologists. Each reader evaluated for the presence or absence of PSMA-positive disease within the prostate bed, pelvic lymph nodes, bones, and soft tissues (extrapelvic lymph nodes and visceral structures). The presence or absence of disease was confirmed by histopathologic analysis if available. For patients who did not have pathologic analysis, a composite of imaging and clinical follow-up was used as the reference standard. RESULTS. The median prostate-specific antigen level was 2.1 ng/mL. Forty-three patients had pathologic correlation, and for 29 patients a composite of imaging and follow-up was used to determine the presence or absence of disease. With substantial to almost perfect interreader reliability by region (κ = 0.78-0.87), 68 Ga-PSMA-11 PET had high sensitivity per region (up to 100%) and per patient (up to 89.8%). It also had high positive predictive value per region (up to 100%) and per patient (up to 91.5%). Sensitivity was highest for bone metastases and lowest for soft-tissue metastases. Positive predictive value was highest for bone metastases and lowest for prostate bed recurrence. CONCLUSION. Gallium-68-labeled PSMA-11 PET is sensitive for prostate cancer metastases in patients with biochemically recurrent prostate cancer. It has high positive predictive value and substantial to almost perfect interrater reliability.

OBJECTIVE. The purpose of this study is to provide a concise summary of the current experience with 68 Ga-labeled prostate-specific membrane antigen (PSMA)-11 imaging of prostate and nonprostate malignancies and benign conditions. CONCLUSION. PSMA is overexpressed in prostate cancer and in the neovasculature of many other malignancies. The relevance of PSMA as a biologic target, coupled with advances in the design, synthesis, and evaluation of PSMA-based radionuclides for imaging and therapy, is anticipated to play a major role in patient care.

Background: Radium-223 improves survival and time to first symptomatic skeletal event in symptomatic bone predominant metastatic castrate-resistant prostate cancer (mCRPC). The imaging response to radium-223 has not been well characterized., Methods: To describe patterns of response and progression with radium-223, we performed a retrospective review of all mCPRC patients who received radium-223 at Duke from 1 June 2013 to 1 June 2015. Radionuclide bone scans obtained at baseline, during, and after treatment were reviewed by two radiologists. The automated bone scan index (aBSI) was generated at each time point using EXINI bone BSI version 2.4. Computed tomography (CT) and magnetic resonance imaging (MRI) clinical radiology reports were reviewed to evaluate for soft tissue, visceral, epidural, and bone progression. Clinical data were abstracted from the electronic health record., Results: We identified 61 men who received at least one dose of radium-223 at Duke during the study period (median, 5 doses; range, 1-6). Among men with imaging during treatment, 2 of 14 (14.3%) had resolution of greater than or equal to 1 lesion on bone scan, 4 of 14 (28.6%) had zero new bone lesions, 10 of 14 (71.4%) had greater than or equal to 1 new bone lesion, 14 of 26 (53.9%) progressed on CT. After radium-223, 6 of 39 (15.4%) had resolution of 1 to 4 bone lesions, 15 of 39 (38.5%) demonstrated zero new bone lesions, 24 of 39 (61.5%) progressed on bone scan, 15 of 37 (40.5%) progressed on CT, and 10 of 34 (29.4%) progressed on both bone scan and CT. No men with zero new bone lesions after radium-223 ultimately progressed in bone alone and only 3 of 15 eventually demonstrated any progression in the bone. aBSI decreased significantly from baseline to after radium-223 among men with zero new bone lesions (median change in aBSI -0.23 [IQR, -1.5, 0.02]) and increased significantly for men with greater than or equal to 1 new postradium bone lesions (median change in aBSI 1.41 [IQR, -0.05, 3.63] [P = 0.018])., Conclusions: Bone and soft tissue progression during and following radium-223 is common in heavily pretreated men with mCRPC. However, stable disease and responses were observed in a subset of patients and may be associated with durable treatment response in the bone. Prospective studies are needed to further investigate the change in aBSI as a biomarker of bone scan response/stabilization and progression following treatment with radium-223., (© 2019 Wiley Periodicals, Inc.)

Background: Enhancer of zeste 2 (EZH2) promotes prostate cancer progression. We hypothesized that increased EZH2 expression is associated with postradiotherapy metastatic disease recurrence, and may promote radioresistance., Methods: EZH2 expression was investigated using immunohistochemistry in diagnostic prostate biopsies of 113 prostate cancer patients treated with radiotherapy with curative intent. Associations between EZH2 expression in malignant and benign tissue in prostate biopsy cores and outcomes were investigated using univariate and multivariate Cox regression analyses. LNCaP and PC3 cell radiosensitivity was investigated using colony formation and γH2AX assays following UNC1999 chemical probe-mediated EZH2 inhibition., Results: While there was no significant association between EZH2 expression and biochemical recurrence following radiotherapy, univariate analysis revealed that prostate cancer cytoplasmic and total EZH2 expression were significantly associated with metastasis development postradiotherapy (P = 0.034 and P = 0.003, respectively). On multivariate analysis, the prostate cancer total EZH2 expression score remained statistically significant (P = 0.003), while cytoplasmic EZH2 expression did not reach statistical significance (P = 0.053). No association was observed between normal adjacent prostate EZH2 expression and biochemical recurrence or metastasis. LNCaP and PC3 cell treatment with UNC1999 reduced histone H3 lysine 27 tri-methylation levels. Irradiation of LNCaP or PC3 cells with a single 2 Gy fraction with UNC1999-mediated EZH2 inhibition resulted in a statistically significant, though modest, reduction in cell colony number for both cell lines. Increased γH2AX foci were observed 24 hours after ionizing irradiation in LNCaP cells, but not in PC3, following UNC1999-mediated EZH2 inhibition vs controls., Conclusions: Taken together, these results reveal that high pretreatment EZH2 expression in prostate cancer in diagnostic biopsies is associated with an increased risk of postradiotherapy metastatic disease recurrence, but EZH2 function may only at most play a modest role in promoting prostate cancer cell radioresistance., (© 2019 The Authors. The Prostate Published by Wiley Periodicals, Inc.)

A six-transmembrane epithelial antigen of prostate-1 (STEAP1) is a newly identified target in prostate cancer. The use of radio-labeled STEAP1-targeting antibodies with positron emission tomography (PET) may allow for detection of sites of metastatic prostate cancer and may refine patient selection for antigen-directed therapies. This was a prospective study in seven patients with metastatic castration-resistant prostate cancer who had at least one archival biopsy that was STEAP1-positive by immunohistochemistry. Patients received intravenous injections of ∼185 MBq and 10 mg of [ 89 Zr]Zr-DFO-MSTP2109A, a humanized IgG1 monoclonal antibody directed against STEAP1. PET/CT images, blood samples, and whole-body counts were monitored longitudinally in six patients. Here, we report on safety, biodistribution, pharmacokinetics, dose estimates to normal tissues, and initial tumor targeting for this group of patients. There was no significant acute or subacute toxicity. Favorable biodistribution and enhanced lesion uptake (in both bone and soft tissue) were observed on imaging using a mass of 10 mg of DFO-MSTP2109A. The best lesion discrimination was seen at the latest imaging time, a median of 6 days postadministration. Pharmacokinetics showed a median serum T 1/2 β of 198 h, volume of central compartment of 3.54 L (similar to plasma volume), and clearance of 19.7 mL/h. The median biologic T 1/2 for whole-body retention was 469 h. The highest mean absorbed doses to normal organs (mGy/MBq) were 1.18, 1.11, 0.78, 0.73, and 0.71 for liver, heart wall, lung, kidney, and spleen, respectively. Excellent targeting of metastatic prostate sites in both bone and soft tissue was observed, with an optimal imaging time of 6 days postadministration. The liver and heart were the normal organs that experienced the highest absorbed doses. The pharmacokinetics were similar to other antibodies without major cross-reactivity with normal tissues. A more detailed analysis of lesion targeting in a larger patient population with correlation to immunohistology and standard imaging modalities has been reported.

A gratifying clinical response obtained in the setting of bilateral orbital metastases from renal neuroendocrine tumor is reported. Methods: A 53-y-old man diagnosed with renal neuroendocrine tumor (MIB1 index, 4%), with symptoms of skeletal and abdominal pain, proptosis, and a decrease in vision of the left eye, was found to harbor bilateral orbital soft-tissue lesions on 68 Ga-DOTATATE PET/CT and MRI in addition to widespread metastatic skeletal lesions and metastatic lymph nodal disease. Despite radiotherapy to the left eye (20 Gy) and long-acting octreotide therapy for 18 mo, his symptoms worsened, with an increase in serum chromogranin A level, and he was considered for 177 Lu-DOTATATE peptide receptor radionuclide therapy (PRRT). Results: There was a significant improvement in skeletal pain, proptosis, and vision after 4 cycles of PRRT (cumulative dose of 22.2 GBq), stable disease on scanning, and a decrease in serum chromogranin A (from 150 to 36.39 ng/mL), with progression-free survival at 18 mo. Conclusion: PRRT through theranostic application of 68 Ga/ 177 Lu-DOTATATE was thus helpful in this uncommon clinical setting., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Cryoablation is a well-established treatment option, proven to be successful in treating local renal cell carcinoma (RCC). We treated a 67-year-old man in an outpatient setting with late onset of a 25 mm solitary soft-tissue metastasis of from RCC with cryoablation. The treatment was performed under sedation and in local anaesthesia. There were no complications during the procedure. The patient did not experience any adverse effects to the treatment. He was able to resume his normal daily routines the day after his treatment. A follow-up CT scan at 3, 8 and 12 months after treatment reported sufficient cryoablation and no sign of recurrence or other metastases., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Prostate cancer (PCa) prognosis and clinical outcome is directly dependent on metastatic occurrence. The bone microenvironment is a favorable metastatic niche. Different biological processes have been suggested to contribute to the osteotropism of PCa such as hemodynamics, bone-specific signaling interactions, and the "seed and soil" hypothesis. However, prevalence of disseminating tumor cells in the bone is not proportional to the actual occurrence of metastases, as not all patients will develop bone metastases. The fate and tumor-reforming ability of a metastatic cell is greatly influenced by the microenvironment. In this review, the molecular mechanisms of bone and soft-tissue metastasis in PCa are discussed. Specific attention is dedicated to the residual disease, novel approaches, and animal models used in oncological translational research are illustrated., (Copyright © 2019 Cold Spring Harbor Laboratory Press; all rights reserved.)