Recurrent Soft Tissue Research Articles

Environmental Methicillin-resistant Staphylococcus aureus Contamination, Persistent Colonization, and Subsequent Skin and Soft Tissue Infection

The longitudinal association among persistent Staphylococcus aureus colonization, household environmental contamination, and recurrent skin and soft tissue infection (SSTI) is largely unexplored to date. To identify factors associated with persistent S aureus colonization and recurrent SSTI in households with children with community-associated methicillin-resistant S aureus (MRSA) SSTI. This 12-month prospective cohort study included 150 children with community-associated MRSA SSTI, 542 household contacts, and 154 pets enrolled from January 3, 2012, through October 20, 2015. A total of 5 quarterly home visits were made to 150 households in the St Louis, Missouri, region. Statistical analysis was performed from September 18, 2018, to January 7, 2020. Covariates used in S aureus strain persistence and interval SSTI models included S aureus colonization and contamination measures, personal hygiene and sharing habits, health history, activities external to the home, and household characteristics (eg, cleanliness, crowding, home ownership, and pets). Serial samples to detect S aureus were collected from household members at 3 anatomic sites, from pets at 2 anatomic sites, and from environmental surfaces at 21 sites. Molecular epidemiologic findings of S aureus isolates were assessed via repetitive-sequence polymerase chain reaction. Individual persistent colonization was defined as colonization by an identical strain for 2 consecutive samplings. Longitudinal, multivariable generalized mixed-effects logistic regression models were used to assess factors associated with persistent S aureus personal colonization, environmental contamination, and interval SSTI. Among 692 household members in 150 households, 326 (47%) were male and 366 (53%) were female, with a median age of 14.82 years (range, 0.05-82.25 years). Of 540 participants completing all 5 samplings, 213 (39%) were persistently colonized with S aureus, most often in the nares and with the strain infecting the index patient at enrollment. Nine pets (8%) were persistently colonized with S aureus. Participants reporting interval intranasal mupirocin application were less likely to experience persistent colonization (odds ratio [OR], 0.44; 95% credible interval [CrI], 0.30-0.66), whereas increasing strain-specific environmental contamination pressure was associated with increased individual persistent colonization (OR, 1.17; 95% CrI, 1.06-1.30). Strains with higher colonization pressure (OR, 1.47; 95% CrI, 1.25-1.71) and MRSA strains (OR, 1.57; 95% CrI, 1.16-2.19) were more likely to persist. Seventy-six index patients (53%) and 101 household contacts (19%) reported interval SSTIs. Individuals persistently colonized with MRSA (OR, 1.56; 95% CrI, 1.17-2.11), those with a history of SSTI (OR, 2.55; 95% CrI, 1.88-3.47), and index patients (OR, 1.54; 95% CrI, 1.07-2.23) were more likely to report an interval SSTI. The study findings suggest that recurrent SSTI is associated with persistent MRSA colonization of household members and contamination of environmental surfaces. Future studies may elucidate the effectiveness of specific combinations of personal decolonization and environmental decontamination efforts in eradicating persistent strains and mitigating recurrent SSTIs.

\u201cPhantom akathisia\u201d in an amputated leg of a sarcoma patient: a case report

BackgroundAkathisia is a rather common extrapyramidal side effect of antipsychotic drugs and antidepressants, often resulting in severe discomfort for patients. However, due to the diversity of symptoms, it is often overlooked. We hereby report a case with akathisia that mainly appeared in an amputated leg.Case presentationsA 60-year-old woman, who had undergone external hemipelvectomy for a recurrent soft tissue sarcoma, was referred to the Department of Psycho-Oncology due to worsening anxiety and restlessness. She was not unconscious or disoriented. Her chief complains included restlessness, an itching sensation in the area corresponding to the amputated left leg, and a feeling as if the lost left leg were raising itself. Detailed examination revealed that she had been administered 10 mg per day of oral prochlorperazine maleate for nausea induced by the oxycodone that had been prescribed to control post-operative pain. Akathisia was suspected and prochlorperazine maleate treatment was discontinued. All the symptoms were alleviated on the next day, and disappeared in 3 days. Eventually, she was diagnosed with akathisia.ConclusionsThis case indicates that the symptoms associated with akathisia can occur in an amputated extremity. Considering two previous reports of “phantom dyskinesia”, extrapyramidal syndromes may result in unusual presentations if occurring in an amputated extremity. Not only should the use of antipsychotic drugs and antidepressants be carefully considered, but also closer observation of psychological symptoms is required after prescription of these drugs because the clinical presentation of akathisia can be various and confusing due to modifications caused by other factors as in this case.

Peripheral gaint cell granuloma in a 9 year old girl

The peripheral giant cell granuloma (PGCG) is a relatively common benign reactive lesion of the oral cavity, originating from the periosteum or the periodontal ligament. It occurs as a result of local trauma or chronic irritation. This article presents a case of peripheral giant cell granuloma with review of literature. A 9 year old girl reported with a nodular lesion in the maxillary right central incisor region of two months duration. The lesion was excised and sent for histopathologic examination. The lesion was diagnosed as PGCG. The usual line of treatment for PGCG is local excision down to the bony base along with elimination of the local etiologic factors. The clinical one year follow up revealed there was no uneventful soft tissue healing or recurrence. Keywords: Peripheral giant cell granuloma, Epulis, Giant cells, First decade, Female.

Recurrent mandibular ameloblastoma in soft tissue and rib graft 17\u2009years after initial presentation

BackgroundAmeloblastoma is the commonest odontogenic tumour of epithelial origin with a high incidence for developing local recurrence. We present a patient who developed local recurrence in both soft tissue and bone graft 17 years after the initial presentation.Case presentationA 75-year-old female with a previous history of right hemimandibulectomy and rib reconstruction for ameloblastoma in 1999 presented to our centre with a large cystic mouth floor swelling, biopsy from which revealed recurrent ameloblastoma. The patient underwent excision of the recurrent mass en bloc with the cystic swelling through oral and cervical approaches. The patient was discharged after 5 days with an uneventful postoperative course and with a free 2-year follow-up from further recurrence.ConclusionAmeloblastoma is a locally aggressive tumour for which wide local excision with adequate margins is the best management approach. Recurrence of ameloblastoma even after adequate resection is not uncommon, and its management is considered a surgical challenge. A very long time may pass between the initial presentation and the development of recurrence.

Impact of Acridine Orange in Patients With Local Recurrent Soft Tissue Sarcoma.

Local recurrence in soft tissue sarcoma (STS) is a risk factor of worse prognosis. Although a few studies have shown that adjuvant therapy with acridine orange (AO) is effective for local control of primary STS, there have been no reports examining its effectiveness for local recurrence. This retrospective study included 36 patients with first local recurrence of STS. Of them, 23 patients received wide excision without AO therapy (Wide group); the other 13 patients received marginal excision with AO therapy (AO group). We compared re-recurrence rates between these two groups. The total re-recurrence rate was 43.5% in the Wide group and 46.2% in the AO group. There was no significant difference in local re-recurrence-free survival and overall survival between the two groups. Adjuvant AO therapy combined with a marginal excision suppresses local re-recurrence rates of individuals with local STS recurrence.

Application of pasteurized tumor-bearing bone replantation for primary malignant bone tumor of extremities

To assess the effectiveness of the pasteurized tumor-bearing bone replantation in treatment of primary malignant bone tumor of extremities. Between February 2012 and June 2016, 13 patients with primary malignant bone tumor of extremities were treated with pasteurized tumor-bearing bone replantation after extensive excision. There were 8 males and 5 females, aged from 11 to 27 years, with an average of 17.4 years. Tumors were located at the mid-upper humerus in 2 cases, the mid-upper femur in 2 cases, the mid-lower femur in 6 cases, the mid-upper tibia in 2 cases, and the middle tibia in 1 case. According to Enneking staging system, 3 patients were classified as stage ⅠB, 5 patients as stage ⅡA, and 5 patients as stage ⅡB. There were 11 cases of osteosarcoma and 2 cases of chondrosarcoma. The disease duration ranged from 3 to 8 months, with an average of 4.8 months. The length of the tumor-bearing bone ranged from 8 to 16 cm, with an average of 12.5 cm. Postoperative follow-up was conducted regularly to evaluate the status of inactivated bone and complications. The limb function was assessed by the Musculoskeletal Tumor Society 93 (MSTS-93) scoring system. All 13 patients were followed up 26-79 months, with an average of 50.5 months. Eleven patients survived without tumors. Two patients had local soft tissue recurrence and underwent amputation, 1 had lung metastasis after amputation and died. All patients had no complications of bone resorption, shortening, and internal fixation disorder. The nonunion of osteotomy occurred in 4 cases. Among them, 3 cases were successfully healed after autologous iliac bone grafting, and 1 case was treated conservatively. The healing time of metaphyseal osteotomy end was 10-15 months (mean, 12.6 months), the healing rate was 90.9% (10/11); the healing time of diaphyseal osteotomy end was 12-21 months (mean, 17.0 months), the healing rate was 72.7% (8/11); and the total healing rate of osteotomy end was 81.8% (18/22). One case had inactivated bone fracture and 1 case had incision dehiscence and infection after operation. At last follow-up, the MSTS-93 score of affected limb ranged from 21 to 28, with an average of 25.3. The procedure of the pasteurized tumor-bearing bone replantation is an effective, simple, and economic way in repair of massive segmental bone defect to save limb function for primary malignant bone tumor of extremities.

Infectious complications as predictors of adverse outcome in a patient with systemic lupus erythematosus (clinical case)

Systemic lupus erythematosus is a systemic autoimmune disease. Over the past decades, great success has been achieved in its treatment. However, mortality in systemic lupus erythematosus is still high. An adverse outcome may occur because of kidney damage, damage of the nervous system, severe hematological disorders, etc. The factor of unfavorable prognosis is infectious complications. The article presents a prospective clinical observation of a faytal case of severe course of systemic lupus erythematosus. The patient was treated in the rheumatology department of the State Regional Clinical Hospital in Saratov from 2007 to 2014. The presence of high disease activity, multiple system disorders — polyarthritis, lupus nephritis, hepatitis, leukopenia, and recurrent necrotizing cutaneous vasculitis required the administration of high doses of immunosuppressive drugs. The progressive course of the disease, resistance to hormonal therapy, the rapid development of infectious complications made the prognosis for the patient’s life extremely unfavorable. Persistent autoimmune leukopenia was the background condition for the development of complications. We used combined therapy — the oral administration of high doses of glucocorticoids together with intravenous injections (pulse therapy), broad-spectrum antibacterial drugs, intravenous immunoglobulin, drugs that improve tissue trophy and microcirculation. It was possible to decrease the disease activity, and also to restore the functional activity of the patient, to maintain low disease activity for 3 years, to prolong the life of a young patient by 8 years. The adverse combination of high activity of systemic lupus erythematosus with recurrent soft tissue infections caused difficulties for the therapy. Administration of adequate doses of cytostatic and biological agents were impossible due to leukopenia and secondary infection, which led to the death of the patient.

Short-term Preoperative Denosumab With Surgery in Unresectable or Recurrent Giant Cell Tumor of Bone.

ObjectiveThe purpose of this retrospective study was to evaluate the clinical and oncological results of combination treatment of short‐term preoperative denosumab (the receptor activator of nuclear factor kappa‐B ligand inhibitor) with surgery in unresectable or recurrent cases of giant cell tumor of the bone (GCTB).MethodsBetween 2016 and 2018, 11 eligible patients (1 man, 10 women, mean age 38.1 years) with grade 3 GCTB were treated with a combination of short‐term (six doses) preoperative denosumab and surgery in a single institution. The clinical, radiological, and pathological alteration after the denosumab treatment were compared. The oncological results of the combination therapy were also recorded. Meanwhile, adverse effects or complications of denosumab, if any, were reported.ResultsThe median follow‐up time after surgical procedure was 30 months (range 13–45 months). After 3–4 denosumab injections, pain relief was observed in all patients. In two spine patients, the neurological status improved after four doses of treatment. Intraoperatively, the margin of the tumor became clear and the intensity of the tumor increased while the blood supply around and within the lesion decreased. Within the lesion, the typically soft and loose tissue were replaced by the tough and dense fibro‐osseous tissue. The mean diameter of the lesion before and after treatment was 61.55 ± 22.49 mm and 51.81 ± 21.12 mm, respectively, and the T‐score was 1.02 (P = 0.32). Variable calcification was observed at the periphery and within the lesion. A total of three patients experienced local recurrence in this study. In the resection group, only one extremity patient had soft tissue recurrence that was treated with en‐bloc excision. In the curettage group, two of three sacral tumor patients had local occurrence. Both refused re‐operation and restarted the monthly denosumab injection thereafter, and the lesions remained stable at the final follow up. Finally, no adverse effects or complications related to denosumab treatment were found.ConclusionFor the unresectable or recurrent GCTB cases, short‐term (six doses) preoperative use of denosumab improved clinical symptoms, decreased the tumor size, and increased the tumor density. The changes in tumors, in turn, simplified the tumor removal manipulation and, subsequently, decreased the local recurrence for the resection surgery. For the curettage, the denosumab‐induced changes had mixed impacts, and shorter term (fewer than six doses) usage may be more appropriate. Our six‐dose regime was deemed safe, while the safety of long‐term use remains unknown.

The construction and analysis of tumor-infiltrating immune cell and ceRNA networks in recurrent soft tissue sarcoma.

Soft tissue sarcoma (STS) is one of the most challenging tumors for medical oncologists, with a high rate of recurrence after initial resection. In this study, a recurrent STS-specific competitive endogenous RNA (ceRNA) network including seven recurrence and overall survival (OS)-associated genes (LPP-AS2, MUC1, GAB2, hsa-let-7i-5p, hsa-let-7f-5p, hsa-miR-101-3p and hsa-miR-1226-3p) was established based on the gene expression profiling of 259 primary sarcomas and 3 local recurrence samples from the TCGA database. The algorithm “cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT)” was applied to estimate the fraction of immune cells in sarcomas. Based on 5 recurrence and OS-associated immune cells (NK cells activated, dendritic cells resting, mast cells resting, mast cells activated and macrophages M1), we constructed a recurrent STS-specific immune cells network. Both nomograms were identified to have good reliabilities (Area Under Curve (AUC) of 5-year survival is 0.724 and 0.773, respectively). Then the co-expression analysis was performed to identify the potential regulation network among recurrent STS-specific immune cells and ceRNAs. Hsa-miR-1226-3p and MUC1 were significantly correlated and dendritic cells resting was related to hsa-miR-1226-3p. Additionally, the expression of MUC1 and dendritic cell marker CD11c were also verified by immunohistochemistry (IHC) assay and multidimensional databases. In conclusion, this study illustrated the potential mechanism of hsa-miR-1226-3p regulating MUC1 and dendritic cells resting might play an important role in STS recurrence. These findings might provide potential prognostic biomarkers and therapeutic targets for recurrent STS.

Efficacy and safety of CT-guided 125I seed implantation as a salvage treatment for locally recurrent head and neck soft tissue sarcoma after surgery and external beam radiotherapy: A 12-year study at a single institution

ObjectivesThe objective of this study was to evaluate the efficacy and safety of CT-guided radioactive 125I seed implantation as a salvage treatment for locally recurrent head and neck soft tissue sarcoma (HNSTS) after surgery and external beam radiotherapy. Methods and MaterialsFrom December 2006 to February 2018, 25 patients with locally recurrent HNSTS after surgery and external beam radiotherapy were enrolled. All the patients successfully underwent CT-guided 125I seed implantation. The primary end points included the objective response rate (ORR) and local progression-free survival (LPFS). The secondary end points were survival (OS) and safety profiles. ResultsAfter 125I seed implantation, the ORR was 76.0%. The 1-, 3-, and 5-year LPFS rates were 65.6%, 34.4%, and 22.9%, respectively, with the median LPFS of 16.0 months. The 1-, 3-, and 5-year OS rates were 70.8%, 46.6%, and 34.0%, respectively, with the median OS of 28.0 months. Furthermore, univariate analyses showed that the recurrent T stage and histological grade were prognostic factors of LPFS, whereas only the histological grade was a predictor of OS. The major adverse events were skin/mucosal toxicities, which were generally of lower grade (≤Grade 2) and were well tolerated. ConclusionsRadioactive 125I seed implantation could be an effective and safe alternative treatment for locally recurrent HNSTS after failure of surgery and radiotherapy. Recurrent T stage and histological grade were the main factors influencing the efficacy.

Outcomes of short segment distal radius resections and wrist fusion with iliac crest bone grafting for giant cell tumor

BackgroundDistal radius is third most common site for occurrence of Giant cell tumor (GCT) of bone. Most of Campanacci grade II & III cases require resection. Reconstructions of these defect are challenging. Though fibular arthroplasty provides mobility at wrist but is fraught with complications of donor site morbidity and instability with wrist pain. Wrist arthrodesis with ulna translocation provides stable reconstruction but is cosmetically less appealing. We present a series of 12 cases of GCT of distal radius treated with short segment (6 cm or less) resections and wrist fusion with iliac crest grafting. We evaluated donor site morbidity, functional and oncological outcomes. ObjectivesTo assess time to union, donor site morbidity, functional and oncological outcomes after wrist fusion with iliac crest bone grafting for distal radius resection (≤6 cm). MethodsRetrospective analysis was performed from a prospectively maintained database between January 2011 and December 2017, 12 patients (7 male and 5 female; 9 primary and 3 recurrent; all Campanacci grade III) were included. Mean age was 29 years (15–41 years) with mean resection length of 5.1 cm (4.5–6 cm). The dominant hand was involved in 6 patients. Time to union, donor site morbidity, functional and oncologiacal outcomes were evaluated. Functional outcomes were evaluated using Musculo-Skeletal Tumor Society (MSTS) score and Patient Rated Wrist Evaluation (PRWE) score. Grip strength and arc of forearm rotation were also evaluated. ResultsAll patients were available for analysis. No symptomatic donor site morbidity was observed. One patient had prominent implant following a fall and delayed union. Mean time to union for 22 osteotomy sites in rest of 11 patients (both proximal and distal) was 6 months (4–11 months). At median follow up of 45 months (18–78 months) 2 patients had soft tissue recurrence, 1 had a stable pulmonary metastasis. Local Recurrence rate was 17%. All patients returned to their pre surgery activity. Mean MSTS score was 25 (19–29) and PRWE score was 12 (6–28). Grip strength and Prono - supination measurements were available in 10 patients. Grip strength was 69% of non operated limb. Mean supination was 53° (0° to 80°) and mean protonation was 73° (40° to 80°). Mean arc of rotation was 126° (80° to 160°). ConclusionReconstruction of distal radius bone defects with Iliac crest bone grafting and wrist arthrodesis retains prono-supination while maintaining wrist girth (cosmesis). The oncologic and functional outcomes make it an acceptable modality in selected cases of distal radius tumours with short resection length (≤6 cm).

1718P - A prospective correlative trial of personalized patient-derived xenograft (PDX) as avatars for drug therapy in patients with metastatic or recurrent soft tissue sarcomas (STS)

BackgroundThe overall benefit from systemic treatments in advanced STS remains modest despite advances in cancer therapies. PDX models may help as avatars in guiding individualized drug use decisions. MethodsIn this prospective single center trial, fresh tumors from patients (pts) with suspected or recently diagnosed STS were engrafted into immunodeficient mice avatars (TumorGraft; Champions Oncology) and tested against a number of standard or non-licensed agents. PDX drug sensitivity profiles were then compared with real-life treatment outcomes. ResultsOf 18 patients enrolled, 3 patients were excluded (consent withdrawal/non-sarcomas). Patient baseline characteristics are summarized in the table. Rate of engraftment was 40% (6/15 pts), while the median time from biopsy to availability of drug sensitivity profile was 379 days (186 – 421). In patients with available drug sensitivity profile (9 different drugs involving 6 pts), the mouse avatar correctly predicted the drug efficacy or lack thereof of drugs in 7 of 9 drug selection time-points (78%) and in 5 of 6 patients (83%).Table1718P Patient baseline characteristicsTableItemEligible patients (n=15)Engrafted patients (n=6)Median age (range)57 (23-76)57 (45-69)Gender (M:F)8:73:3Subtype - Liposarcoma - Leiomyosarcoma -UPS -Others5 3 1 62 2 1 1 ConclusionsPDX avatars can accurately predict drug response in STS pts. The rate of engraftment and time taken to produce drug sensitivity profiles are limitations for using this platform in guiding treatment for individual patients in real time. Nonetheless, the high degree of clinical predictability of this PDX platform may offer therapeutic value for personalized oncology approaches. Legal entity responsible for the studyAlbiruni Razak. FundingMount Sinai Sarcoma Foundation. DisclosureG. Paris: Full / Part-time employment: champions oncology. M. Mancini: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: Champions Oncology. A.R.R. Albiruni: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (self): Lilly; Advisory / Consultancy, Research grant / Funding (self): Merck; Research grant / Funding (self): CASI Pharmaceuticals; Research grant / Funding (self): Novartis; Research grant / Funding (self): Deciphera; Research grant / Funding (self): Kayopharm Therapeutics; Research grant / Funding (self): Pfizer; Research grant / Funding (self): Roche/ Genentech; Research grant / Funding (self): Boston Biomedical; Research grant / Funding (self): Bristol-Myers Squibb; Research grant / Funding (self): MedImmune; Research grant / Funding (self): Amgen; Research grant / Funding (self): GlaxoSmithKline; Research grant / Funding (self): Blueprint Medicines; Research grant / Funding (self): AbbVie; Research grant / Funding (self): Adaptimmune. All other authors have declared no conflicts of interest.

Efficacy and Safety of CT-Guided 125I Seed Implantation As a Salvage Treatment for Locally Recurrent Head and Neck Soft Tissue Sarcoma after Surgery and External Beam Radiotherapy: A 12-Year Study at a Single Institution

The treatment for locally recurrent head and neck soft tissue sarcoma (HNSTS) after failure of previous surgery and external beam radiotherapy (EBRT) remains a problematic challenge without widely accepted recommendations. We aimed to evaluate the efficacy and safety of CT-guided radioactive 125I seed (RIS) implantation for the treatment of locally recurrent HNSTS after surgery and EBRT and analyze the prognostic factors of efficacy. Between December 2006 and February 2018, 25 patients with locally recurrent HNSTS after failure of surgery and EBRT were erolled. We re-staged the recurrent tumors according to the American Joint Committee On Cancer (AJCC) System for soft tissue sarcoma of the head and neck sarcoma (8th ed, 2017) when analyzing the data. All these patients successfully underwent treatment with computed tomography (CT)-guided 125I seed implantation. The postoperative evaluation of seed and dose distribution was performed immediately after surgery. The primary endpoints included the objective overall response rate (ORR) and local progression-free survival (LPFS), and the secondary endpoints were overall survival (OS) and safety profiles. Following 125I seed implantation brachytherapy, the ORR was 72.0%, median LPFS was 16.0 months and median OS was 28.0 months. Furthermore, the 1-, 2-, 3-, 4- and 5-year LPFS rates were 65.6%, 48.1%, 34.4%, 22.9%, and 22.9% respectively and the 1-, 2-, 3-, 4- and 5-year survival rates were 70.8%, 56.9%, 46.6%, 40.8%, and 34.0%, respectively. Multivariate analyses showed that the recurrent T stage (T4 vs ≤ T3；hazard ratio [HR]= 4.020; 95% confidence interval [CI]= 1.117-14.466; P=0.033) and histological grade (G3 vs ≤ G2；HR= 3.260; 95% CI= 1.031-10.306; P=0.044) were independent prognostic factors of LPFS, whereas only the histological grade (G3 vs ≤ G2；HR= 3.230; 95% CI=1.061-9.834; P=0.039) was an independent predictor of OS. The major adverse events were skin/mucosal toxicities, which were generally of lower grade (≤ grade 2) and well tolerated. RIS implantation could be an effective and safe alternative treatment for locally recurrent HNSTS after failure of surgery and EBRT. Recurrent T stage and histological grade were the main factors influencing the efficacy.

Efficacy and Dosimetry Prognostic Factors of Ultrosound/CT-Guided 125I Seed Implantation for Locally Recurrent Soft Tissue Sarcoma

To observe the effect of ultrasound / CT guided radioactive 125I seed implantation in the treatment of recurrent soft tissue sarcoma and its relationship with physical dosimetry prognostic factors. The data of 37 patients with recurrent soft tissue sarcoma who received ultrasound/CT-guided 125I seed implantation from November 2005 to December 2015 were retrospectively analyzed. The local progression-free survival rate and overall survival rate were evaluated. The relationship of local progression-free survival rate and overall survival with physical dosimetric parameters was analyzed. Thirty-seven patients, 20 males and 17 females, with a median age of 53 years (16-79 years), received a median radiation dose of 60 Gy (28 Gy-120 Gy). The median tumor volume was 46.8 cm3 (0.5-252.2 cm3), the median particle activity was 0.67 mCi (0.4-0.84 mCi), and the median implanted particle number was 60 (3-158). The median follow-up time was 20 months (range: 1∼144 months). The median overall survival time was 20.0 months (95% CI 16.4-23.6 months). The overall survival rates of 1, 3 and 5 years were 62.2%, 34.3% and 27.7% respectively. The median local progression-free time was 63.0 months. The 1-year, 3-year and 5-year local progression-free survival rates were 68.9%, 55.0% and 47.1%, respectively. Correlation analysis showed that HI was positively correlated with total survival and local progression-free survival (P = 0.001). Multivariate analysis showed that HI (> 0.25) was an independent prognostic factor for long overall survival (P = 0.048, HR 0.39), and D90 (> 110 Gy) was an independent prognostic factor for long local progression-free survival (P = 0.024, HR 0.17). Ultrasound/CT guided 125I seed implantation is a safe and effective method for the treatment of recurrent soft tissue sarcoma with high local control rate. The HI and D90 of the postoperative plan maybe affect the therapeutic efficacy.

Novel \u201cdouble-strut\u201d fibula ankle arthrodesis for large tumor-related bone defect of distal tibia

BackgroundReconstruction for large bone defect of distal tibia after wide resection of tumor is difficult, and the best option remains controversial. This study presents a novel “double-strut” fibula ankle arthrodesis for this issue.MethodsNine patients with malignant or aggressive tumors of distal tibia underwent novel “double-strut” fibula ankle arthrodesis after wide tumor resection were retrospectively reviewed. We assessed the bone union time, complications and oncology outcome clinically and radiographically. The Musculoskeletal Tumor Society (MSTS) score and the Foot and Ankle Outcome Score (FAOS) were used to evaluate the functional outcome.ResultsThe average followup period was 53 ± 46 months. There was no deep infection or graft fracture observed in this series. Internal fixation loosening was found in one case. In these patients, eight achieved union at both proximal and distal junctions, while one achieved union only distally. The mean union time of the proximal junctions and distal junctions was 10.5 ± 1.6 months and 8.7 ± 2.3 months, respectively. The mean postoperative MSTS score was 83% ± 8%. The subscales of FAOS indicating the most problem was Sport and Recreation Function with a mean score of 18 ± 11. At the final follow-up, one of them (1/9, 11%) experienced local recurrence in soft tissue and received another resection surgery, and four (4/9, 44%) patients developed lung metastases.ConclusionsFor large bone defect of distal tibia, this novel “double-strut” fibula reconstruction can be a viable alternative, which is capable of achieving durable ankle fusion and functional salvaged limb with low rate of complications.

Changes in the tumor immune microenvironment in resected recurrent soft tissue sarcomas.

Little is known about how the tumor immune microenvironment (TIME) is modulated in recurrent soft tissue sarcomas (STS). We evaluated CD8+ T cells, CD20+ B cells, Foxp3+ regulatory T cells (Tregs), and programmed cell death ligand 1 (PD-L1) in 72 paired pre-recurrent (1st resected) versus post-recurrent (2nd resected) STS by immunohistochemistry. Correlations with time to recurrence and prognosis were determined. We found that CD8, PD-L1, CD20, and Foxp3-positive cell counts changed in post-recurrent STS. PD-L1-positive tumor cell and lymphocyte counts increased in post-recurrent STS, whereas CD8+ T cell counts decreased. Changes in CD8+ T cell, CD20+ B cell, and PD-L1+ lymphocyte counts were associated with the time interval between surgeries. At admission, fewer CD8+ T cells were detected in patients with relapse than in newly diagnosed patients. Furthermore, post-recurrent STS with fewer CD8+ T cells compared with pre-recurrent STS were more likely to exhibit re-recurrence. The change in CD8+ T cells was positively associated with overall survival. In multivariate analyses, a decrease in CD8+ T cell counts in post-recurrent STS was an independent unfavorable prognostic factor. The TIME differs between pre-recurrent STS and post-recurrent STS. The variation in CD8+ T cells and PD-L1 positivity may have essential roles during tumor relapse and provides a basis for determining therapeutic strategies.

Abstract 1995: Low-dose eribulin suppresses lung metastasis of osteosarcoma in vitro and in vivo

Abstract Osteosarcoma is the most common malignant bone tumor among children and adolescents. The prognosis of osteosarcoma remains poor in these thirty years because the effective therapeutic option for lung metastasis has not been established. Therefore, the development of effective metastatic therapy is required. Eribulin, a new microtubule targeting agent, has been indicated for recurrent breast cancer and malignant soft tissue sarcoma. Clinical trials of eribulin showed that it elongated overall survival period rather than disease-free survival period. These results motivated us to investigate the effect of eribulin on metastasis suppression of osteosarcoma. Here, we examined the inhibitory effect of eribulin on lung metastasis and its mechanism using murine osteosarcoma metastasis model. In vivo experiments: Eribulin was intravenously injected by two administration methods, (1) high dose administration on standard schedule; 1 mg/kg q7d × 2, (2) frequent low dose administration; 0.3 mg/kg q4d × 4. Both methods sufficiently reduced circulating tumor cells in blood and inhibited lung metastasis. Method (1) also inhibited primary tumor growth, but induced severe body weight loss. Method (2) had little effect on primary tumor growth and showed little body weight loss. In vitro experiments: The IC50 concentration of eribulin for metastatic osteosarcoma cell line, LM8, was about 20 nM. Pharmacokinetics studies have shown that eribulin intravenously administered at 1 mg/kg presents with a brief high-concentration phase which surges to ≥100 nM followed by a long low-concentration phase which stabilizes at ~10 nM for one week. These two phases sandwiched the IC50 concentration of eribulin. Thus, we separately investigated that the effect of high and low eribulin concentrations on LM8. High eribulin concentrations induced cell cycle arrest and apoptosis in LM8, whereas low eribulin concentrations changed cell morphology and decreased cell migration through reducing directionality and focal adhesion turnover. Reduced peripheral localization of adenomatous polyposis coli (APC) protein by eribulin might cause these effects. In a three-dimensional collagen culture system, low eribulin concentrations inhibited tumor cell infiltration and colony formation. The anti-metastatic effects at low concentrations backed-up the results of our in vivo experiments by frequent low dose administration method. Eribulin is a potential therapeutic option for lung metastasis of osteosarcoma. Frequent low dose administration method with fewer side effects enables the combination with other chemotherapeutic agents and broadens the application of eribulin as an anti-metastatic drug for osteosarcoma. Citation Format: Kenta Watanabe, Yoshihiro Yui, Satoru Sasagawa, Kayo Suzuki, Masahiko Kanamori, Taketoshi Yasuda, Tomoatsu Kimura. Low-dose eribulin suppresses lung metastasis of osteosarcoma in vitro and in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1995.

Abstract 1253: MDM2 inhibitor APG-115 synergizes with CDK4/6 inhibitors in a patient-derived xenograft model of dedifferentiated liposarcoma

Abstract Liposarcoma is a rare but highly recurrent soft tissue neoplasm. Combination of surgery and radiotherapy is the main treatment for liposarcoma patients while chemotherapy remains experimental and limited depends on disease subtypes. Well-differentiated and dedifferentiated liposarcoma (WDLPS/DDLPS) represents ~50% of all diagnosed liposarcoma and their benefit from chemotherapy has been documented to be minimal. Concomitant amplifications of MDM2 and CDK4 are frequently found in WDLPS/DDLPS patients, suggesting that the combination with two targeted agents may worth further development for the treatment. APG-115 is a potent, selective, orally bioavailable small molecule inhibitor of MDM2-p53 protein-protein interaction and thus activates tumor suppression activity of p53 in p53 wild-type tumors. Currently, APG-115 is in clinical development as a single agent or in combination with PD-1 blockade immunotherapy for solid tumors, including sarcoma. To further explore the sensitive patient population and predictive biomarkers for APG-115, in this study, we evaluated the effect of the combined MDM2/CDK4 inhibition in p53 wild-type, MDM2 and CDK4 amplified liposarcoma using a preclinical xenograft tumor model derived from a dedifferentiated liposarcoma patient (PDX). Tumor-bearing mice were treated with MDM2 inhibitor APG-115, CDK4 inhibitors palbociclib/ribociclib, or their combinations. In the first experiment, APG-115 administered at 40 mg/kg as a single agent demonstrated antitumor activity in the DDLPS PDX model. In comparison with the single agents, the combination treatment with APG-115 and palbociclib or APG-115 and ribociclib exerted synergistic antitumor effects, resulting in T/C values of 16.9% and 27.1%, respectively (T/C value, average tumor volumes in treatment group vs. the vehicle control group). Partial tumor regression (PR) was achieved in 1/5 animals in both combination treatment groups but not in single arms. Another independent experiment with a higher dose of APG-115 (80 mg/kg) combined with palbociclib showed further improved antitumor activity with T/C value of 7.0% (2/5 PR). Collectively, our results suggest that the combination therapy of APG-115 and a CDK4 inhibitor may benefit WDLPS/DDLPS patients with p53 wild-type, and MDM2 and CDK4 amplifications clinically. Citation Format: Douglas D. Fang, Guoqin Zhai, Chunhua Xu, Qingyang Gu, Jingwen Wang, Saijie Zhu, Dajun Yang, Yifan Zhai. MDM2 inhibitor APG-115 synergizes with CDK4/6 inhibitors in a patient-derived xenograft model of dedifferentiated liposarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1253.

Comparative DNA cytometry of primary and recurrent soft tissue sarcomas.

e22516 Background: Soft tissue sarcomas (STS) are aggressive tumors with a high degree of recurrence. Radical resection within healthy tissues allows to reduce the recurrence percentage to 25-30% without subsequent therapy. The literary analysis has shown that the study of various biological properties of primary and recurrentsoft tissue tumorsis being conducted. However, currently there is a lack of information to understand the reasons for STS recurrence. The goal of investigation was to reveal the distinctive features of the DNA content and cell distribution in the phases of the cell cycle of recurrent STS. Methods: DNA cytometry in the tumor tissue of 30 primary soft tissue sarcomas and 30 STS recurrences was carried out using the method of flow cytofluorometry. The tumor ploidy and cell distribution in the cell cycle phases were analyzed. Results: A number of differences in the DNA cytometric parameters of primary and recurrent STS have been revealed, they include: an increase in the proportion of aneuploid tumors in case of recurrence, the number of tumors with DNA index within the mitotic cycle, an increase in the proportion of cells in G2+M- phase of diploid and aneuploid tumors and a decrease in S- phase of aneuploid ones. It has been shown that with a G2 differentiation degree, the proportion of cells in G2+M, S- and proliferation index of recurrent STS is significantly lower than the primary parameters. An increase in the proportion of cells in G2+M- phase and a decrease in the rate of proliferation of recurrent STS, depending on the stage, are shown only in case of stage III. Conclusions: The revealed features of DNA content and cell cycle of tumor cells of soft tissue sarcomas will allow to approach to understanding of biological bases of recurrence of this malignant disease.

Efficacy and dosimetry prognostic factors of image guided 125I seed implantation for locally recurrent soft tissue sarcoma.

11073 Background: To observe the effect of ultrasound / CT guided radioactive 125I seed implantation in the treatment of recurrent soft tissue sarcoma and its relationship with physical dosimetry prognostic factors. Methods: The data of 37 patients with recurrent soft tissue sarcoma who received ultrasound/CT-guided 125I seed implantation from November 2005 to December 2015 were retrospectively analyzed. The local progression-free survival rate and overall survival rate were evaluated. The relationship of local progression-free survival rate and overall survival with physical dosimetric parameters was analyzed. Results: Thirty-seven patients, 20 males and 17 females, with a median age of 53 years (16-79 years), received a median radiation dose of 60 Gy (28 Gy-120 Gy). The median tumor volume was 46.8 cm3 (0.5-252.2 cm3), the median particle activity was 0.67 mCi (0.4-0.84 mCi), and the median implanted particle number was 60 (3-158). The median follow-up time was 20 months (range: 1~144 months). The median overall survival time was 20.0 months (95% CI 16.4-23.6 months). The overall survival rates of 1, 3 and 5 years were 62.2%, 34.3% and 27.7% respectively. The median local progression-free time was 63.0 months. The 1-year, 3-year and 5-year local progression-free survival rates were 68.9%, 55.0% and 47.1%, respectively. Correlation analysis showed that HI was positively correlated with total survival and local progression-free survival (P = 0.001). Multivariate analysis showed that HI ( > 0.25) was an independent prognostic factor for long overall survival (P = 0.048, HR 0.39), and D90 ( > 110 Gy) was an independent prognostic factor for long local progression-free survival (P = 0.024, HR 0.17). Conclusions: Ultrasound/CT guided 125I seed implantation is a safe and effective method for the treatment of recurrent soft tissue sarcoma with high local control rate. The HI and D90 of the postoperative plan maybe affect the therapeutic efficacy.