Sclerosing epithelioid fibrosarcoma of the kidney.

A woman in her 20s presented with headache and back pain and was found to have a left renal mass with bony metastases. She underwent nephrectomy, and on histopathology was initially diagnosed with stage 4 clear cell sarcoma of the kidney. She underwent palliative radiation and chemotherapy; however, the disease progressed and she came to our centre. We started her on second-line chemotherapy and submitted her tissue blocks for review. Due to her age and lack of sclerotic stroma in the tissue, we had our doubts about the diagnosis and hence, tissue sample was submitted for next-generation sequencing (NGS). NGS detected an EWSR1::CREBL1 fusion, clinching the final diagnosis of sclerosing epithelioid fibrosarcoma of the kidney, a singular diagnosis rarely reported in the literature. Currently, the patient is post her third line of chemotherapy, is on maintenance, and is doing well and has resumed her daily activities.

Long-term Development of Fibrosarcoma in the Practice of Emergency Medical Teams: a Case Report.

Fibrosarcoma is a relatively rapidly growing, poorly delineated spindle cell tumour. It has generally good prognosis and rarely metastasizes. Soft tissue sarcomas account for less than 1% of all malignancies in adults. High rates of sarcomas are, for example, seen in patients with tuberous sclerosis complex. This paper presents the case of a patient with knee joint destruction caused by a fibrosarcoma, on account of which an emergency medical team was summoned several times. We present data from three medical rescue team interventions to a patient with a tumour in the left lower leg. The data was obtained from the documentation generated during the interventions: dispatch order record (DOR) and medical emergency treatment report (METR). The patient had a history of the following chronic diseases (ICD-10): E11.8, I50.9, I10, and M15. Two interventions involved patient transportation to a hospital, whereas the third intervention was completed in the patient's home. The fibrosarcoma caused only slight pain. Frequent bleeding from an open cancerous wound was the main problem in this patient. Difficulty in wound healing could have been related to complications of diabetes mellitus and the patients advanced age.

Oncologic outcomes in myxofibrosarcomas: the role of a multidisciplinary approach and surgical resection margins.

BACKGROUNDS: Myxofibrosarcomas (MFS) are malignant soft tissue sarcomas with an infiltrative growth pattern and propensity for local recurrence(LR).We aimed to assess our management of MFS and make recommendations about the role of a multidisciplinary team approach and margin widths. METHODS: Fifty-seven patients were identified with MFS treated at a single sarcoma centre between 1998 and 2020. Patients were stratified based on whether they presented for a planned resection (59.6%) or after an unplanned resection (40.4%) performed at a non-specialized facility. All patients underwent radiotherapy before definitive surgery. RESULTS: 73.7% underwent a combined onco-plastic approach. The 5 year LRFS rate was 78.2% (84.4%, planned, versus 70.1%, unplanned, P = 0.194) and found comparable oncological outcomes between the planned and unplanned groups for the 5 year metastasis free survival (74.5% versus 86.1%, P = 0.257), disease free survival (70.1% versus 72.4%, P = 0.677), and Overall Survival (64.5% versus 75.9%, P = 0.950). Margin width ≥ 2 cm was obtained in 84.2% of cases and improved local control (HR = 0.22; 95% CI 0.06-0.81; P = 0.023), metastasis (HR = 0.24; 95% CI 0.07-0.80; P = 0.019) and mortality rates (HR = 0.23; 95% CI 0.09, 0.61; P = 0.003) compared to <2 cm. Margin width > 3 cm did not further affect oncological outcomes. CONCLUSION: Our study shows that a multidisciplinary team approach allows the achievement of low local recurrence rate and good oncological outcomes of myxofibrosarcomas, regardless of presentation status. We recommend a minimum of 2 cm margin width.

Epidemiologic Survey of Myxofibrosarcoma Using Data from the Bone and Soft Tissue Tumor Registry in Japan.

BACKGROUND: Myxofibrosarcoma is a common sarcoma among older patients, with locally infiltrative behavior and a predilection for local postoperative recurrence. Some studies have reported the factors affecting prognosis, although only a few have mentioned the previous staging classification systems. This study investigated the clinical overview and prognosis of myxofibrosarcoma to determine the optimal treatment. METHODS: This retrospective study analyzed the records of 349 patients with myxofibrosarcoma in the nationwide Bone and Soft Tissue Tumor Registry in Japan from 2006 to 2015. Clinical features, treatment options, and patient outcomes were investigated. RESULTS: Ultimately, 349 patients were identified. The overall survival rates were 93.1% at 2 years and 84.3% at 5 years. A multivariate analysis was performed using the Cox proportional hazards model. The study identified four significant prognostic factors for survival: tumor size, depth, compartment status, and location. The prognostic score was calculated by summing the scores of all the factors. The overall survival rate was 69.3% at 5 years for the patients with prognostic scores of 6 or higher. Conversely, the patients with prognostic scores of 2 or lower had a survival rate of 95.6% at 5 years. CONCLUSIONS: Among myxofibrosarcomas, those larger than 5 cm, deep-seated, invaded into the external compartment, or in axial body parts were associated with a significantly worse prognosis. Adjuvant radiotherapy and chemotherapy did not contribute significantly to a better prognosis. Previous staging classification systems are impractical for prognosis prediction. Therefore, new classifications are needed. Further research on new treatment methods for patients with a poor prognosis will be crucial in the future.

Characterization of the immune cell infiltration landscape in myxofibrosarcoma to aid immunotherapy.

Myxofibrosarcoma (MFS) is a highly malignant subtype of soft tissue sarcoma, accounting for 5% of cases. Immunotherapy guided by immune cell infiltration (ICI) is reportedly a promising treatment strategy. Here, MFS samples (n = 104) from two independent databases were classified as ICI clusters A/B/C and gene clusters A/B/C. Then, a close relationship between ICI and gene clusters was established. We found that the features of these clusters were consistent with the characteristics of immune-inflamed tumors (cluster C), immune-desert tumors (cluster B), and immune-excluded tumors (cluster A). Moreover, cluster C was sensitive to immunotherapy. Finally, an independent ICI score was established to predict the therapeutic effect, which has prospects for application in guiding immunotherapy during clinical practice.

The Efficacy of Radiation is Enhanced by Metformin and Hyperthermia Alone or Combined Against FSaII Fibrosarcoma in C3H Mice.

The effects of mild-temperature hyperthermia (MTH) and metformin, alone or in combination, on the efficacy of high-dose hypofractionated radiation against experimental tumors were investigated. FSaII fibrosarcoma grown subcutaneously in the hind legs of C3H mice was irradiated with a single 15 Gy dose using a 60Co irradiator. The radio frequency capacitive method was used to heat the tumors at 41.0°C for 30 min. Metformin was intraperitoneally (i.p.) administered daily to tumor-bearing mice at a dose of 150 mg/kg. The expression levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and programmed cell death-ligand 1 (PD-L1) were determined by immunohistochemical staining of the excised tumor tissues. The apoptosis of tumor cells in vivo was quantified by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and cleaved caspase-3 staining of the excised tumor tissues. Irradiation of tumors markedly increased the expression of HIF-1α, VEGF, and PD-L1, and MTH and metformin used either alone or in combination significantly abrogated the radiation-induced upregulation of these proteins. MTH and metformin alone or combined increased the radiation-induced apoptosis in tumor cells and enhanced the radiation-induced suppression of tumor growth. The findings indicated that the increased tumor response to 15 Gy irradiation by MTH and metformin alone or in combination was due, in part, to the abrogation of the radiation-induced upregulation of HIF-1α and its downstream targets VEGF and PD-L1.

Feline Injection-Site Sarcoma Complete Remission After Treatment with Isopathic medicine: a case repor

Feline injection-site sarcomas (FISS) were described for the first time in 1991. They are neoplasms of mesenchymal origin that appear in body regions routinely used for the application of vaccines or other injections [1]. Those are very aggressive tumours that relapse and have a high rate of mortality. The tumour can appear between 3 months and 3 years after the injection, but in some cases, it can happen after 15 years of the vaccineor otherinjections. Isopathy is one approach of homeopathy, in which the biological agent thatcausesa disease are prepared in high dilution to treat the same disease. This case report is about a 13-year-old mix breed spay cat. In September 2019 it received the vaccine Rabsin® (Boehringer Ingelheim) and 4 months later the owner noticed a lump at the injection area. One year later (September 2020) the lump start growing rapidly and on January 12th, 2021,started the appointments.The other veterinarians recommend euthanasia since the tumour was very bigand the catwasnot mild, was losing weightand appetite. The owner wanted to try another treatment before euthanasia since the cat was still active, interacting with the other cat and the people at the house.The lump was located on her back, in the end of the right ribcage, and it was around 7cm of diameter. It wasfirmandattachedto the muscles. AnIsopathy medicine with the same vaccinewas prepared, being the isotherapic 12CH administered 5 drops BID.Beside the isopathyvitaminsof Bcomplex and Omega 3were prescribed.The cat was seen every15 days andcontact telephonically was kept as well. The treatment started on January 19th, 2021. On January 21st, 2021,all the tumour was ulcerated and looser. On February 2nd,2021 the potencywas changedto 14CH, 5 drops, BID. On February 4ththe tumour felt away and was sent for histopathological study. On February 20th, 2021,the result described it as a Fibrosarcoma grade II. The ulcer that appeared after the tumour felt away became a big wound and the ownerstarted cleaning itwith propolis and lavender oleateeveryday anditwas controlledonce a week. OnMarch31st, 2021,the catwas eating well,strong, not mild,didnot allowedit to be cleaned. The woundseems to be more superficial,largerand it appears thata small lump was growing again.Isotherapic 15CH, 5 drops once a weekwas indicated.On April4th, 2021,the cat waseating well, good general conditionand the small lump that was growing wasshrinkingand the wound becoming more superficial. OnApril 9th,2021the cat seems painful, not eating well, constipated. Isopathy was suspended and started with Meloxican0,1mg/kg SID for 3 days.Was indicatedNatrum muriaticum30CH, 5 drops every hour, total 3 treatments and then once a day. On April 13th, 2021,the cat was better, defecate. But since April 9ththe cat could never be stable again. It has ups and downs and was treated withdifferent homeopathic remedies (Natrum muriaticum30Ch, Silicea200CHand Silicea1000CH, Staphisagria 200CH)until June 8th, 2021,when it was euthanised.No necropsy was done. The question was,what happenedwith the catsince itwas getting better?The following aphorisms could explain it:§156 "...The restoration, however, leads to the goal of the cure, if it is not preventedby strange medicinal influence, by errors in the lifestyle or by passions." And§10"With no vital powerthe material organism is not capable of any sensation, function or self-preservation..."[2].The informed consent formwas obtained from the owner of the cat.

Regulatory T cell differentiation is controlled by αKG-induced alterations in mitochondrial metabolism and lipid homeostasis.

Suppressive regulatory T cell (Treg) differentiation is controlled by diverse immunometabolic signaling pathways and intracellular metabolites. Here we show that cell-permeable α-ketoglutarate (αKG) alters the DNA methylation profile of naive CD4 T cells activated under Treg polarizing conditions, markedly attenuating FoxP3+ Treg differentiation and increasing inflammatory cytokines. Adoptive transfer of these T cells into tumor-bearing mice results in enhanced tumor infiltration, decreased FoxP3 expression, and delayed tumor growth. Mechanistically, αKG leads to an energetic state that is reprogrammed toward a mitochondrial metabolism, with increased oxidative phosphorylation and expression of mitochondrial complex enzymes. Furthermore, carbons from ectopic αKG are directly utilized in the generation of fatty acids, associated with lipidome remodeling and increased triacylglyceride stores. Notably, inhibition of either mitochondrial complex II or DGAT2-mediated triacylglyceride synthesis restores Treg differentiation and decreases the αKG-induced inflammatory phenotype. Thus, we identify a crosstalk between αKG, mitochondrial metabolism and triacylglyceride synthesis that controls Treg fate.

Primary Fibrosarcoma of the Breast: Case Report of a Rare Breast Neoplasm.

Breast fibrosarcoma is an uncommon primary breast neoplasm. We report a case of a 57-year old woman who presented at our facility with a right breast mass having histomorphological and immunohistochemical features consistent with fibrosarcoma. She had simple mastectomy and an uneventful hospital stay. The mass recurred 4-weeks later for which she had supportive care and started on cyclical chemotherapy (Adriamycin, Cyclophosphamide and Dacarbazine). She was referred for haemostatic radiotherapy and her clinic follow-up scheduled.

Le fibrosarcome du sein est une tumeur primitive du sein rare. Nous rapportons le cas d'une femme de 57 ans qui s'est présentée dans notre établissement avec une masse mammaire droite présentant des caractéristiques histomorphologiques et immunohistochimiques compatibles avec un fibrosarcome. Elle a eu une mastectomie simple et un séjour à l'hôpital sans incident. La masse est réapparue 4 semaines plus tard pour laquelle elle a reçu des soins de soutien et a commencé une chimiothérapie cyclique (Adriamycine, Cyclophosphamide et Dacarbazine). Elle a été référée pour une radiothérapie hémostatique et son suivi clinique a été programmé.

Non-rhabdomyosarcoma soft tissue sarcomas diagnosed in patients at a young age. An overview of clinical, pathological, and molecular findings.

OBJECTIVE: Disease spectrum in pediatric sarcoma differs substantially from adults. We report a cohort of very young children with non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) detailing their molecular features, treatment, and outcome. METHODS: We report features of consecutive children (age <2 years) with NRSTS (2000-2017). Archival pathological material was re-reviewed, with additional molecular techniques applied where indicated. RESULTS: Twenty-nine patients (16 females, 55%) were identified (median age 6 months; range 0-23). Most common diagnoses included infantile fibrosarcoma (IFS, n = 14, 48%), malignant rhabdoid tumor (MRT, n = 4, 14%), and undifferentiated sarcoma (n = 4, 14%). Twenty-seven of 29 (93%) had tumor molecular characterization to confirm diagnosis. Clinical presentation included a swelling/mass (n = 23, 79%). Disease extent was localized (n = 20, 69%), locoregional (n = 6, 21%), or metastatic (n = 3, 10%). Seventeen of 29 (59%) who underwent surgery achieved complete resection (R0). Other treatments included conventional chemotherapy (n = 26, 90%), molecularly targeted therapies (n = 3, 10%), and radiation (n = 5, 17%). At last follow-up (median 3 years; range 0.3-16.4), 23 (79%) were alive, disease-free and six (21%) had died of disease. All patients with IFS were alive and all those with MRT died. A cancer predisposition syndrome (CPS) was confirmed in three of 10 (30%) genetically tested patients. CONCLUSION: We recommend tumor molecular characterization in all young patients including evaluation for CPS to optimize treatment options and prognostication.

High-intensity focused ultrasound treatment as an alternative regimen for myxofibrosarcoma.

Myxofibrosarcoma is a common soft-tissue sarcoma in elderly patients, characterized by an infiltrative growth pattern and a high risk for persistent local recurrence. A 35-years-old woman was diagnosed with myxofibrosarcoma on the right upper arm and the tumor is surgically resected. The tumor relapsed 7 months later. Then the patient received five cycles of low power cumulative high-intensity focused ultrasound (HIFU) treatments, which completely ablated the tumor without complications. Now the patient is disease free with a high quality of life more than 30 months. This case indicates HIFU ablation might be a novel, promising therapy for recurrent myxofibrosarcoma.

Sclerosing Epithelioid Fibrosarcoma: A Distinct Sarcoma With Aggressive Features.

Since its original description in 1995, the concept of sclerosing epithelioid fibrosarcoma (SEF) as a distinctive tumor has evolved in the literature. Subsequent studies suggested that the presence of low grade fibromyxoid sarcoma (LGFMS)-like zones, occasional FUS gene rearrangements, and immunoreactivity for MUC4 all pointed to a close inter-relationship with LGFMS; however, more recent studies showed that SEF is genetically distinct from LGFMS with predominantly EWSR1-CREB3L1 fusion and complex secondary genomic alterations. To better understand the relationship between these tumors, we studied 51 cases of SEF, the largest reported series to date, and directly compared them to a previously published series of LGFMS from the same institution. The male-to-female ratio was 1.4:1 with a median age of 45 years. Tumors occurred primarily in the lower extremity (12), intra-abdominal area/visceral organs (9) and chest wall/paraspinal region (9) with a median size of 8.2 cm. The median follow-up was 49 months in 45 patients: 12 developed local recurrences and 36 developed metastases, mainly to lung and bone. Molecular studies showed EWSR1 gene rearrangement in 13 cases, 3' deletion of EWSR1 in 6, monosomy for EWSR1 in 2; FUS gene rearrangements in 3; EWSR1-CREB3L1 fusion in 7; EWSR1-CREB3L2 fusion in 1; and YAP1-KMT2A fusion in 2. Overall survival of SEF was significantly less compared with LGFMS (P≤0.0001). These results indicate that SEF is a distinct sarcoma that behaves more aggressively than LGFMS with a shorter survival, higher metastatic rate, and greater propensity to involve deep soft tissue and bone.

Prevalence, clinical features and prognosis of malignant solid tumors in infants: a 14-year study.

The onset of malignant solid tumors in infants is insidious and difficult to diagnose on time. The purpose of our study is to provide a theoretical basis for clinical diagnosis by retrospective analysis of the data in the past 14 years. Here, we retrospectively collected the clinical data of infants aged 0-12 months with malignant solid tumors in Beijing Tongren Hospital Affiliated to Capital Medical University from May 2005 to May 2019. The epidemiology, clinical characteristics, treatments and prognosis were statistically analyzed. A total of 496 infants (294 males and 202 females) with malignant solid tumors were analyzed. The main period of onset was 1-11 months. The most common tumor was retinoblastoma (RB, 51.8%), followed by hepatoblastoma (HB, 26.6%), neuroblastoma (NB, 10.5%), rhabdomyosarcoma (RMS, 3.4%), malignant renal tumors (3.2%), infantile fibrosarcoma (IFS, 1.6%), malignant teratoma (1.2%), Ewing's sarcoma (ES, 0.8%), medulloblastoma (MB, 0.4%) and inflammatory myofibroblastic tumor (IMT, 0.4%). The median follow-up time was 32 months (range 2-162 months). The 1-year, 3-year, and 5-year overall survival of all patients were 97.3%, 89.2%, and 81.1%, respectively, and event-free survival was 94.7%, 84.8%, and 75.8%, respectively. In conclusion, as a special group, malignant solid tumors in infants are complex, heterogeneous, and relatively rare. The prognosis of RB, HB, NB, RMS, malignant renal tumors, IFS, malignant teratoma, ES, MB, and IMT, were excellent duo to timely diagnosis and rational treatment.

[Tumors affecting the temporomandibular joint - a literature review]. / Tumeurs de l'articulation temporomandibulaire ­ revue de la littérature.

Benign and malign tumors can affect the temporomandibular joint (TMJ) as any other articulation. Nevertheless, TMJ tumors are rare and mostly benign. Their clinical expression is varied including symptomatology similar to TMJ dysfunctional disorders, otologic or neurologic pathologies. In some cases, they remain totally asymptomatic. Hence, diagnosis is difficult since the symptomatology can be misleading with TMJ dysfunctional disorders or otologic disorders wrongly diagnosed. There is thus frequently a long delay between symptoms onset and diagnosis. The great variety of TMJ lesions explains the wide range of possible treatment modalities, mostly based on surgery. We provide here a review of the lesions originating from the TMJ. Tumoral or cystic mandibular lesion affecting the TMJ through local extension will not be discussed. Osteoma, osteoid osteoma, osteoblastoma, chondroma, osteochondroma, chondroblastoma, tenosynovial giant cell tumors, giant cell lesions, non-ossifying fibroma, hemangioma, lipoma or Langerhans cell histiocytosis are all possible diagnosis among the benign tumors found in the TMJ. Pseudotumors include synovial chondromatosis and aneurysmal bone cyst. Finally, malign tumors of the TMJ include mainly sarcomas (osteosarcoma, chondrosarcoma, synovial sarcoma, Ewing sarcoma, and fibrosarcoma), but also multiple myeloma and secondary metastases. We will review the clinical, radiological and histological aspects of each of these lesions. The treatment and the recurrence risk will also be discussed.

Pilot study on the therapeutic potential of radiofrequency magnetic fields: growth inhibition of implanted tumours in mice.

The present study investigated possible therapeutic effects of radiofrequency or hypomagnetic fields on the growth rate of two types of implanted tumours. To this end, mice with implanted fibrosarcoma and pancreatic tumours were exposed continuously to a 2 µT, 10 MHz radiofrequency magnetic field (MF) perpendicular to a 45 µT static MF or to a hypomagnetic (~0.4-1 µT) field. The reasoning for a 10 MHz treatment was based on a current theoretical explanation for MF effects, which predicts a resonance phenomenon in this frequency range. Radiofrequency MFs reduced consistently the growth rate of two implanted tumour types (by ~30% in both cases). Also, hypomagnetic field hindered tumour growth in both tumour types, but the observation was not statistically significant with fibrosarcoma tumours. In conclusion, although experiments included a limited number of animals, the results indicate that MFs may offer a novel therapeutic strategy in the treatment of cancer.

Optimized Dose of Dendritic Cell-based Vaccination in Experimental Model of Tumor Using Artificial Neural Network.

Previous studies have demonstrated that maturation of dendritic cells (DCs) by pathogenic components through pathogen-associated molecular patterns (PAMPs) such as Listeria monocytogenes lysate (LML) or CpG DNA can improve cancer vaccination in experimental models. In this study, a mathematical model based on an artificial neural network (ANN) was used to predict several patterns and dosage of matured DC administration for improved vaccination. The ANN model predicted that repeated co-injection of tumor antigen (TA)-loaded DCs matured with CpG (CpG-DC) and LML (List-DC) results in improved antitumor immune response as well as a reduction of immunosuppression in the tumor microenvironment. In the present study, we evaluated the ANN prediction accuracy about DC-based cancer vaccines pattern in the treatment of Wehi164 fibrosarcoma cancer-bearing mice. Our results showed that the administration of the DC vaccine according to ANN predicted pattern, leads to a decrease in the rate of tumor growth and size and augments CTL effector function. Furthermore, gene expression analysis confirmed an augmented immune response in the tumor microenvironment. Experimentations justified the validity of the ANN model forecast in the tumor growth and novel optimal dosage that led to more effective treatment.

The Biology of Myxofibrosarcoma: State of the Art and Future Perspectives.

BACKGROUND: Myxofibrosarcoma (MFS) is among the most highly complex sarcoma types. Molecular cytogenetic studies have identified a high level of genomic complexity. SUMMARY: This review provides an update of the current research related to MFS, with particular emphasis on emerging mechanisms of tumorigenesis and their potential therapeutic impact. Many novel possible molecular markers have been identified, not only for prognostication in MFS, but also to serve as possible therapeutic targets, and thereby improve clinical outcomes. However, the molecular pathogenesis of MFS remains incompletely understood. Key Messages: Patients suffering from advanced MFS might benefit from expanded molecular evaluation in order to detect specific expression profiles and identify drug-able targets. Moreover, immunotherapy represents an intriguingly perspective due to the presence of "T-cell inflamed" tumor microenvironment.

NKTR-214 immunotherapy synergizes with radiotherapy to stimulate systemic CD8+ T cell responses capable of curing multi-focal cancer.

BACKGROUND: High-dose radiotherapy (RT) is known to be immunogenic, but is rarely capable of driving clinically relevant abscopal antitumor immunity as monotherapy. RT is known to increase antigen presentation, type I/II interferon responses, and immune cell trafficking to irradiated tumors. Bempegaldesleukin (NKTR-214) is a CD122-preferential interleukin 2 (IL-2) pathway agonist that has been shown to increase tumor-infiltrating lymphocytes, T cell clonality, and increase PD-1 expression. NKTR-214 has increased drug half-life, decreased toxicity, and increased CD8+ T cell and natural killer cell stimulation compared with IL-2. METHODS: Animals bearing bilateral subcutaneous MCA-205 fibrosarcoma or CT26 colorectal tumors were treated with NKTR-214, RT, or combination therapy, and tumor growth of irradiated and abscopal lesions was assessed. Focal RT was delivered using a small animal radiation research platform. Peripheral and tumor-infiltrating immune phenotype and functional analyses were performed by flow cytometry. RNA expression profiling from both irradiated and abscopal lesions was performed using microarray. RESULTS: We demonstrate synergy between RT of a single tumor and NKTR-214 systemic therapy resulting in dramatically increased cure rates of mice bearing bilateral tumors compared with RT or NKTR-214 therapy alone. Combination therapy resulted in increased magnitude and effector function of tumor-specific CD8+ T cell responses and increased trafficking of these T cells to both irradiated and distant, unirradiated, tumors. CONCLUSIONS: Given the increasing role of hypofractionated and stereotactic body RT as standard of care treatments in the management of locally advanced and metastatic cancer, these data have important implications for future clinical trial development. The combination of RT and NKTR-214 therapy potently stimulates systemic antitumor immunity and should be evaluated for the treatment of patients with locally advanced and metastatic solid tumors.

5-Aminolevulinic acid tumor paint and photodynamic therapy for myxofibrosarcoma: an in vitro study.

BACKGROUND: 5-Aminolevulinic acid (5-ALA), a fluorescent contrast agent, has been used for tumor paint and photodynamic therapy (PDT) for various tumors, but its use with soft tissue sarcomas is not well documented. Myxofibrosarcoma, a subtype of soft tissue sarcoma with a high local recurrence rate, may benefit from similar types of treatment. The purpose of this study was to analyze the effects of 5-ALA tumor paint and PDT on a myxofibrosarcoma cell line. METHODS: Tumor paint was assessed by exposing micromass pellets of human adipose-derived stromal (ADS) cells or myxofibrosarcoma (MUG-Myx1) cells to 5-ALA. Cell pellets were then visualized using a microscope at established excitation and emission wavelengths. Corrected total cell fluorescence was calculated per accepted protocols. Photodynamic therapy was similarly assessed by exposing ADS and MUG-Myx1 cells to 5-ALA, with subsequent analysis via flow cytometry and real-time confocal microscopy. RESULTS: The use of 5-ALA tumor paint led to a selective fluorescence in MUG-Myx1 cells. Findings were confirmed by flow cytometry. Interestingly, flow cytometry results showed progressive selective cell death with increasing 5-ALA exposure as a result of the PDT effect. PDT was further confirmed using confocal microscopy, which revealed progressive cellular bubble formation consistent with advancing stages of cell death-a finding that was not seen in control ADS cells. CONCLUSIONS: 5-ALA tumor paint and PDT were successfully used on a human myxofibrosarcoma cell line (MUG-Myx1). Results from this study showed both selective fluorescent tagging and selective cytotoxicity of 5-ALA toward malignant myxofibrosarcoma cells, while sparing benign adipose control cells. This finding was further confirmed in a dramatic time-lapse video, visually confirming active, targeted cell death. 5-ALA's two-pronged application of selective tumor identification and cytotoxicity may transform surgical and medical approaches for treating soft tissue sarcomas.