A Retrospective Analysis of Systemic Oncologic Treatment in Older Patients With Advanced Soft-tissue Sarcoma.

BACKGROUND/AIM: Almost half of all patients with soft-tissue sarcoma are over 65 years of age, and the proportion of older patients is increasing. Despite this, they have been underrepresented in clinical trials and only limited data are available to guide treatment decisions. The aim of this study was to investigate treatment patterns and outcomes in older patients with soft-tissue sarcoma. PATIENTS AND METHODS: Patients over 50 years old treated for advanced soft-tissue sarcoma at the Helsinki University Hospital between January 2000 and July 2020 were included. Data on patient and tumor characteristics, treatment, and survival were retrospectively collected. A total of 152 patients were included: 14.5% (n=22) were over 75 years old, 34.2% (n=52) were 65-74 and 51.3% (n=78) were 50-64 years old. RESULTS: The outcomes of the oldest group differed from those of younger patients; they were more likely to receive single-agent treatment as first-line therapy (90.9% vs. 28.8% and 24.4%, p<0.001) and had the lowest relative dose-intensity (70% vs. 88% and 95%, p<0.05). They experienced grade three to four hematological adverse events less frequently (38.1%, 56.9% and 72.7%, respectively, p=0.031), and received fewer lines of treatment (median of 1, 2 and 2, respectively, p=0.01). In patients aged ≥75 years, there was no association between further lines of therapy and improved survival. Compared to the youngest group, the oldest patients had a greater risk of dying (hazard ratio=1.7, 95% confidence interval=1.0-2.8, p=0.041) and their median overall survival was only 7.4 months, compared to 14.3 and 12.9 months in the two younger groups. CONCLUSION: These findings suggest that older patients tolerate chemotherapy when treatment is tailored to their needs but may not benefit as much as younger patients.

Ultra-low-dose computed tomography and chest X-ray in follow-up of high-grade soft tissue sarcoma-a prospective comparative study.

Ultra-low-dose computed tomography (ULD-CT) may combine the high sensitivity of conventional computed tomography (CT) in detecting sarcoma pulmonary metastasis, with a radiation dose in the same magnitude as chest X-ray (CXR). Fifty patients with non-metastatic high-grade soft tissue sarcoma treated with curative intention were recruited. Their follow-up involved both CXR and ULD-CT to evaluate their different sensitivity. Suspected findings were confirmed by conventional CT if necessary. Patients with isolated pulmonary metastases were treated with surgery or stereotactic body radiation therapy (SBRT) with curative intent if possible. The median effective dose from a single ULD-CT study was 0.27 mSv (range 0.12 to 0.89 mSv). Nine patients were diagnosed with asymptomatic lung metastases during the follow-up. Only three of them were visible in CXR and all nine in ULD-CT. CXR had therefore only a 33% sensitivity compared to ULD-CT. Four patients were operated, and one had SBRT to all pulmonary lesions. Eight of them, however, died of the disease. Two patients developed symptomatic metastatic recurrence involving extrapulmonary sites+/-the lungs between two imaging rounds. ULD-CT has higher sensitivity for the detection of sarcoma pulmonary metastasis than CXR, with a radiation dose considerably lower than conventional CT.Clinical trial registration: NCT05813808. 04-14-2023.

PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma.

Liposarcomas (LPSs) are a heterogeneous group of malignancies that arise from adipose tissue. Although LPSs are among the most common soft-tissue sarcoma subtypes, precision medicine treatments are not currently available. To discover LPS-subtype-specific therapy targets, we investigated RNA sequenced transcriptomes of 131 clinical LPS tissue samples and compared the data with a transcriptome database that contained 20,218 samples from 95 healthy tissues and 106 cancerous tissue types. The identified genes were referred to the NCATS BioPlanet library with Enrichr to analyze upregulated signaling pathways. PDE3A protein expression was investigated with immunohistochemistry in 181 LPS samples, and PDE3A and SLFN12 mRNA expression with RT-qPCR were investigated in 63 LPS samples. Immunoblotting and cell viability assays were used to study LPS cell lines and their sensitivity to PDE3A modulators. We identified 97, 247, and 37 subtype-specific, highly expressed genes in dedifferentiated, myxoid, and pleomorphic LPS subtypes, respectively. Signaling pathway analysis revealed a highly activated hedgehog signaling pathway in dedifferentiated LPS, phospholipase c mediated cascade and insulin signaling in myxoid LPS, and pathways associated with cell proliferation in pleomorphic LPS. We discovered a strong association between high PDE3A expression and myxoid LPS, particularly in high-grade tumors. Moreover, myxoid LPS samples showed elevated expression levels of SLFN12 mRNA. In addition, PDE3A- and SLFN12-coexpressing LPS cell lines SA4 and GOT3 were sensitive to PDE3A modulators. Our results indicate that PDE3A modulators are promising drugs to treat myxoid LPS. Further studies are required to develop these drugs for clinical use.

Local relapse of soft tissue sarcoma of the extremities or trunk wall operated on with wide margins without radiation therapy.

BACKGROUND: The quality of surgical margins is the most important factor affecting local control in soft tissue sarcoma (STS). Despite this, there is no universally accepted consensus on the definition of an adequate surgical margin or on which patients should be offered radiation therapy. This study focuses on local control and its prognostic factors in patients with trunk wall and extremity STS. METHODS: Adult patients with a final diagnosis of trunk wall or extremity STS referred to a single tertiary referral centre between August 1987 and December 2016 were identified from a prospective institutional database. Patients were treated according to a protocol instituted in 1987. The classification of surgical margins and indications for radiation therapy were based on anatomy and strict definition of surgical margins as metric distance to the resection border. Local treatment was defined as adequate if patients received either surgery with wide margins alone or marginal surgery combined with radiation therapy. Margins were considered wide if the tumour was excised with pathological margins greater than 2.5 cm or with an uninvolved natural anatomical barrier. After treatment, patients were followed up with local imaging and chest X-ray: 5 years for high-grade STS, 10 years for low-grade STS. RESULTS: A total of 812 patients were included with a median follow-up of 5.8 (range 0.5-19.5) years. Forty-four patients had a grade 1 tumour: there were no instances of recurrence in this group thus they were excluded from further analysis. Five-year local control in the 768 patients with grade 2-3 STS was 90.1 per cent in patients receiving adequate local treatment according to the protocol. Altogether, 333 patients (43.4 per cent) were treated with wide surgery alone and their 5-year local control rate was 91.1 per cent. Among patients treated with wide surgery alone, deep location was the only factor adversely associated with local relapse risk in multivariable analysis; 5-year local control was 95.3 per cent in superficial and 88.3 per cent in deep-sited sarcomas (hazards ratio 3.154 (95% c.i. 1.265 to 7.860), P = 0.014). CONCLUSION: A high local control rate is achievable with surgery alone for a substantial proportion of patients with STS of the extremities or superficial trunk wall.

Patterns of Metastatic Recurrence of Genetically Confirmed Myxoid Liposarcoma.

BACKGROUND: Most sarcomas metastasize predominantly to the lungs, and chest x-ray, or computed tomography, is the most commonly used staging investigation. Myxoid liposarcomas (MLSs) are rare tumors with a tendency to metastasize to extrapulmonary loci. The aim of this study was to assess the locations of the first metastases in MLS patients, to guide the design of effective staging and follow-up imaging protocols. METHODS: Patients treated for MLS between 1987 and 2017 were identified in a prospectively maintained register. Histology of the tumors was reassessed. In addition, the presence of one of the pathognomonic gene translocations was confirmed, uniquely for a retrospective series. The surgical and oncological outcomes were reviewed. A comprehensive review of the literature was performed on the metastatic pattern of MLS, including series with 10 or more MLS patients with metastatic disease. RESULTS: A total of 32 patients with genetically confirmed MLS were identified, with a median follow-up of 7.6 years. Seven patients (22%) developed metastatic disease, five initially intra-abdominally and only one to the lungs. The comprehensive review included 14 series with 1853 patients, 348 (19%) of whom had metastases. The location of the first metastases was soft tissues in 32% of patients, intra-abdominal in 26%, pulmonary in 24%, and bone in 17%. CONCLUSIONS: MLSs metastasize often intra-abdominally and to extra-abdominal soft tissues. Thus, whole-body imaging may be indicated during the initial assessment and follow-up of these patients.

PROX1 transcription factor controls rhabdomyosarcoma growth, stemness, myogenic properties and therapeutic targets.

Rhabdomyosarcoma (RMS) is an aggressive pediatric soft-tissue cancer with features of skeletal muscle. Because of poor survival of RMS patients and severe long-term side effects of RMS therapies, alternative RMS therapies are urgently needed. Here we show that the prospero-related homeobox 1 (PROX1) transcription factor is highly expressed in RMS tumors regardless of their cell type of origin. We demonstrate that PROX1 is needed for RMS cell clonogenicity, growth and tumor formation. PROX1 gene silencing repressed several myogenic and tumorigenic transcripts and transformed the RD cell transcriptome to resemble that of benign mesenchymal stem cells. Importantly, we found that fibroblast growth factor receptors (FGFR) mediated the growth effects of PROX1 in RMS. Because of receptor cross-compensation, paralog-specific FGFR inhibition did not mimic the effects of PROX1 silencing, whereas a pan-FGFR inhibitor ablated RMS cell proliferation and induced apoptosis. Our findings uncover the critical role of PROX1 in RMS and offer insights into the mechanisms that regulate RMS development and growth. As FGFR inhibitors have already been tested in clinical phase I/II trials in other cancer types, our findings provide an alternative option for RMS treatment.

Tensin2 Is a Novel Diagnostic Marker in GIST, Associated with Gastric Location and Non-Metastatic Tumors.

GIST is a rare soft tissue sarcoma, for which KIT and DOG1 are used as highly sensitive diagnostic markers. Other diagnostic markers include CD34, protein kinase C θ, deficiency of succinate dehydrogenase complex subunit B, carbonic anhydrase II, and type I insulin-like growth factor receptor. We investigated the role of TNS2 as a diagnostic biomarker by using immunohistochemistry in 176 GISTs and 521 other sarcomas. All GISTs expressed TNS2, with intermediate or high expression in 71.4% of samples. The majority (89.8%) of other sarcomas were negative for TNS2, and intermediate to strong staining was only seen in 2.9% of samples. Strong TNS2 staining was associated with gastric location (gastric 52.8% vs. non-gastric 7.2%; p < 0.001), absence of metastases (non-metastatic tumors 44.3% vs. metastatic tumors 5.9%; p = 0.004), female sex (female 45.9% vs. male 33.8%; p = 0.029), and tumors of lower risk categories (very low or low 46.9% vs. intermediate 51.7% vs. high 29.0%; p = 0.020). TNS2 expression did not correlate with overall survival or metastasis-free survival. No associations between TNS2 expression and KIT/PDGFRA mutation status, tumor size, mitotic count, or age of the patient were detected. The results provide conclusive evidence for the value of TNS2 as a sensitive and specific diagnostic biomarker for GIST.

Visual Counting and Automated Image-analytic Assessment of Ki-67 and their Prognostic Value in Synovial Sarcoma.

Background: Ki-67 is a widely used proliferation marker reflecting prognosis in various tumors. However, visual assessment and scoring of Ki-67 suffers from marked inter-observer and intra-observer variability. We aimed to assess the concordance of manual counting and automated image-analytic scoring methods for Ki-67 in synovial sarcoma. Patients and Methods: Tissue microarrays from 34 patients with synovial sarcoma were immunostained for Ki-67 and scored both visually and with 3DHistech QuantCenter. Results: The automated assessment of Ki-67 expression was in good agreement with the visually counted Ki-67 (r Pearson =0.96, p<0.001). In a Cox regression model automated [hazard ratio (HR)=1.047, p=0.024], but not visual (HR=1.063, p=0.053) assessment method associated high Ki-67 scores with worse overall survival. Conclusion: The automated Ki-67 assessment method appears to be comparable to the visual method in synovial sarcoma and had a significant association to overall survival.

Serum Concentration of Thymidine Kinase 1 (TK1) as a Tumor Marker in Soft Tissue Sarcomas.

BACKGROUND/AIM: The aim of this prospective study was to determine whether serum Thymidine kinase -1 (TK1) could serve as a tumor marker in soft tissue sarcomas (STS). PATIENTS AND METHODS: A total of 48 patients diagnosed with localized STS were included. None had received preoperative oncological treatment. Samples were collected before and after surgery and TK1 levels measured with the AroCell TK210 ELISA. RESULTS: Mean preoperative TK1 was 0.32 µg/l, range=0.11-1.47, and 18 cases (38%) had values above the reference limit (0.41 µg/l). Mean postoperative TK1 was 0.35 µg/l (0.06-0.86). In patients with preoperative values above the reference limit, TK1 decreased significantly after surgery (n=13, p=0.001). We found no association between increased preoperative TK1 and age, sex, tumor size, grade, and the presence of vascular invasion or necrosis. CONCLUSION: TK1 has limited use as a tumor marker in localized STS.

Radiation-associated angiosarcoma of the breast: analysis of diagnostic tools in a registry-based population.

BACKGROUND: Radiation-associated angiosarcoma of the breast (RAASB) is a serious late consequence caused by breast cancer treatment. Initial symptoms are often inconspicuous, thus contributing to diagnostic delay. Most previous studies of the diagnostic aspects of RAASB are case reports. PURPOSE: To perform a complete review of the imaging findings and biopsy methods in a nationwide RAASB cohort. MATERIAL AND METHODS: RAASB patients were identified from a national cancer registry and additional patients were included from our hospital. All available information from imaging (mammogram [MGR], ultrasound [US], magnetic resonance imaging [MRI], and computed tomography [CT]) and biopsies was reviewed. The sensitivity of imaging and biopsy methods for detection of RAASB was calculated. RESULTS: Fifty-eight patients with RAASB were found. Fourteen MGR, 30 US, 24 MRI, and 25 CT studies were available for evaluation. The sensitivity of MGR, US, MRI, and CT for detection of RAASB was 43%, 50%, 92%, and 84%, respectively. Superior sensitivity was demonstrated for punch biopsy (84%) and incisional biopsy (93%) compared to fine-needle aspiration cytology (0%) and core needle biopsy (18%). CONCLUSION: MRI and CT have comparable sensitivity for detection of RAASB, while MGR and US are unreliable. However, negative findings in MRI or CT must be interpreted with caution. Punch biopsy and incisional biopsy are the preferred biopsy methods.

Expression of markers of stem cell characteristics, epithelial-mesenchymal transition, basal-like phenotype, proliferation, and androgen receptor in metaplastic breast cancer and their prognostic impact.

BACKGROUND: Metaplastic breast cancer (MpBC) is a heterogeneous subtype of invasive mammary carcinoma associated with epithelial-mesenchymal transition (EMT) and cancer stem cell characteristics. Data regarding prognostic markers and potentially actionable targets for therapy are still limited. The present study aimed to characterize the immunohistochemical landscape of this rare malignancy and to identify potential prognostic factors and targets for therapy. MATERIAL AND METHODS: A total of 75 patients diagnosed with MpBC over a 15-year period were included in the study. We performed immunohistochemical analyses for Ki-67 (MIB-1), epidermal growth factor receptor (EGFR), cytokeratin 5/6, vimentin, CD44, and androgen receptor (AR) and correlated their expression with clinicopathologic features and clinical outcomes. The p-values for survival analyses were corrected for multiple testing (threshold 0.01). RESULTS: Most tumors expressed CK5/6 (73%), EGFR (59%), CD44 (81%), and vimentin (87%). Eighty-nine percent had a high Ki-67 index. Eighty-four percent were classified as basal-like (CK 5/6 or EGFR positive). AR was expressed in 21% of the tumors. The basal-like phenotype was significantly (p = 0.009) associated with inferior disease-free (DFS) and breast-cancer-specific overall survival (BCOS) with borderline significance (p = 0.01). In addition, a low Ki-67 index was associated with improved DFS (p = 0.033) and BCOS (p = 0.03). CONCLUSION: Most MpBCs express basal markers (CK5/6, EGFR), epithelial-mesenchymal transition marker vimentin, and the stem cell marker CD44. Expression of basal-like markers was significantly related to inferior DFS. All the 11 patients with a lack of expression of basal markers survived without relapse.

Validity of five foot and ankle specific electronic patient-reported outcome (ePRO) instruments in patients undergoing elective orthopedic foot or ankle surgery.

BACKGROUND: Patient-reported outcomes (PROs) are widely accepted measures for evaluating outcomes of surgical interventions. As patient-reported information is stored in electronic health records, it is essential that there are valid electronic PRO (ePRO) instruments available for clinicians and researchers. The aim of this study was to evaluate the validity of electronic versions of five widely used foot and ankle specific PRO instruments. METHODS: Altogether 111 consecutive elective foot/ankle surgery patients were invited face-to-face to participate in this study. Patients completed electronic versions of the Foot and Ankle Ability Measure (FAAM), the Foot and Ankle Outcome Score (FAOS), the modified Lower Extremity Function Scale (LEFS), the Manchester-Oxford Foot Questionnaire (MOXFQ), and the Visual Analogue Scale Foot and Ankle (VAS-FA) on the day of elective foot and/or ankle surgery. Construct validity, coverage, and targeting of the scales were assessed. RESULTS: Based on general and predefined thresholds, construct validity, coverage, and targeting of the ePRO versions of the FAAM, the FAOS, the MOXFQ, and the VAS-FA were acceptable. Major issues arose with score distribution and convergent validity of the modified LEFS instrument. CONCLUSIONS: The ePRO versions of the FAAM, the FAOS, the MOXFQ, and the VAS-FA provide valid scores for foot and ankle patients. However, our findings do not support the use of the modified LEFS as an electronic outcome measure for patients with orthopedic foot and/or ankle pathologies.

Structural validity of the Finnish Manchester-Oxford Foot Questionnaire (MOXFQ) using the Rasch model.

BACKGROUND: The 16-item patient-reported Manchester-Oxford Foot Questionnaire (MOXFQ) with subscales of pain, social interactions, and walking/standing has been claimed for strongest scientific evidence in measuring foot and ankle complaints. This study tests the validity of the Finnish MOXFQ for orthopaedic foot and ankle population using the Rasch analysis. METHODS: We translated the MOXFQ into Finnish and used that translation in our study. MOXFQ scores were obtained from 183 patients. Response category distribution, item fit, coverage, targeting, item dependency, ability to measure latent trait (unidimensionality), internal consistency (Cronbach's alpha), and person separation index (PSI) were analyzed. RESULTS: Fifteen of the items had ordered response categories and/or sufficient fit statistics. The subscales provided coverage and targeting. Some residual correlation was noted. Removing one item in the pain subscale led to a unidimensional structure. Alphas and PSIs ranged between 0.68-0.90 and 0.67-0.92, respectively. CONCLUSIONS: Despite some infractions of the Rasch model, the instrument functioned well. The subscales of the MOXFQ are meaningful for assessing patient-reported complaints and outcomes in orthopaedic foot and ankle population.

Multidisciplinary Oncovascular Surgery is Safe and Effective in the Treatment of Intra-abdominal and Retroperitoneal Sarcomas: A Retrospective Single Centre Cohort Study and a Comprehensive Literature Review.

OBJECTIVE: Radical excision of retroperitoneal or intra-abdominal soft tissue sarcomas may necessitate vessel resection and reconstruction. The aim of this study was to assess surgical results of retroperitoneal or intra-abdominal sarcomas involving major blood vessels. METHODS: This was a retrospective single centre cohort study and a comprehensive review of literature. Patients with retroperitoneal or intra-abdominal sarcomas treated by the oncovascular team in Helsinki University Hospital from 2010 to 2018 were reviewed for vascular and oncological outcomes. A comprehensive literature review of vascular reconstructions in patients with retroperitoneal sarcoma was performed. RESULTS: Vascular reconstruction was performed in 17 patients, 11 of whom required arterial reconstructions. Sixteen of the operations were sarcoma resections; the post-operative diagnosis for one patient was thrombosis instead of the presumed recurrent leiomyosarcoma. Early graft thrombosis occurred in two venous and one arterial reconstruction. Late thrombosis was detected in three (18%). The median follow up was 27 (range 0-82) months. Of the patients with sarcoma resections 5 (31%) died of sarcoma and further 4 (25%) developed local recurrence or new distant metastases. The comprehensive review of literature identified 37 articles with 110 patients, 89 of whom had inferior vena cava reconstruction only. Eight arterial reconstructions were described. Late graft thrombosis occurred in 14%. The follow up was 0-181 months, during which 57% remained disease free and 7% died of sarcoma. CONCLUSION: Vascular reconstructions enable radical resection of retroperitoneal and intra-abdominal sarcomas in patients with advanced disease. The complex operations are associated with an acceptable rate of serious peri-operative complications and symptomatic thrombosis of the repaired vessel is rare. However, further studies are needed to assess the performance of the vascular reconstructions in the long term.

Single centre 30-year experience in treating retroperitoneal liposarcomas.

BACKGROUND AND OBJECTIVES: Liposarcomas form a diverse group of tumors that represent the majority of retroperitoneal soft tissue sarcomas. Radical excision of these retroperitoneal liposarcomas is often challenging due to their large size and proximity to visceral organs and major vessels. Here we present the 30-year experience of our multidisciplinary sarcoma team in the treatment of these tumors and analysis of factors influencing survival. METHODS: Patients with retroperitoneal liposarcomas treated in Helsinki University Hospital from 1987 to 2017 were reviewed. Local recurrence-free survival, metastases-free survival, and disease-specific survival were assessed with Kaplan-Meier analysis, and factors influencing survival were evaluated with Cox regression. RESULTS: A total of 107 patients were identified. The median follow-up time was 5.4 years (interquartile range: 2.2-8.8 years). Local recurrence developed in 72% and metastases in 15% during follow-up. The 5-year disease-free survival was 31% and disease-specific survival was 66%. The multifactorial analysis revealed histological type and grade as predictors of disease-specific survival (P < .01) while multifocality carried a poor prognosis for local recurrence (P = .02) and higher histological grade for metastases (P < .01). CONCLUSIONS: Retroperitoneal liposarcomas rarely metastasize but tend to recur locally. For tumors that have been resected with macroscopically clear margins, histological, type, and grade are significant predictors of survival.

Treatment and Prognosis of Radiation-Associated Breast Angiosarcoma in a Nationwide Population.

BACKGROUND: Radiation-associated angiosarcoma of the breast (RAASB) is an aggressive malignancy that is increasing in incidence. Only a few previous population-based studies have reported the results of RAASB treatment. METHODS: A search for RAASB patients was carried out in the Finnish Cancer Registry, and treatment data were collected to identify prognostic factors for survival. RESULTS: Overall, 50 RAASB patients were identified. The median follow-up time was 5.4 years (range 0.4-15.6), and the 5-year overall survival rate was 69%. Forty-seven (94%) patients were operated on with curative intent. Among these patients, the 5-year local recurrence-free survival, distant recurrence-free survival, and overall survival rates were 62%, 75%, and 74%, respectively. A larger planned surgical margin was associated with improved survival. CONCLUSIONS: We found that the majority of RAASB patients were eligible for radical surgical management in this population-based analysis. With radical surgery, the prognosis is relatively good.

(Neo)adjuvant chemotherapy and interdigitated split-course hyperfractionated radiation in high risk soft tissue sarcoma - Results from a large single-institution series.

A single-institution series using a (neo)adjuvant chemotherapy and interdigitated hyperfractionated split-course radiation therapy (CRT) treatment protocol for soft tissue sarcoma was reviewed. Our specific aims were to study recurrence rates and long-term toxicity. Between 1998 and 2016, 89 patients with non-metastatic soft tissue sarcoma were treated with surgery combined with six courses of doxorubicin and ifosfamide and hyperfractionated radiation therapy (42-60 Gy/1.5 Gy twice daily). Patients were considered being at high risk if tumour malignancy grade was high and the tumour fulfilled at least two of the following criteria: size >8 cm, presence of necrosis or vascular invasion. The mean age of the patients was 50.7 years. With a median follow-up of 5.4 years for survivors, the local control rate was 81.4%. Six (7%) patients progressed during neoadjuvant CRT. Seven (8%) patients discontinued the treatment due to toxicity. Eighty-six patients were operated and three (3%) of these developed a long-term complication. The estimated metastasis-free survival was 47.6% and overall survival 53.0% at five years. The limb-salvage rate was 93%. The limb-salvage rate, local control and complication rates were good in these patients with high risk soft tissue sarcoma. Metastases-free survival and overall survival rates were less satisfactory, reflecting the aggressive nature of these tumours.

Long-term results of surgical resection of lung metastases from soft tissue sarcoma: A single center experience.

BACKGROUND: A single-institution experience of pulmonary metastasectomy in soft tissue sarcoma (STS) was retrospectively reviewed. Our specific aim was to examine, whether the resection of pulmonary metastases could be curative. We also compared overall survival (OS) of patients after complete or incomplete pulmonary resection and nonsurgical treatment. METHODS: Between 1987 and 2016, 1580 patients were treated for STS with curative intent by Soft Tissue Sarcoma Group at Helsinki University Hospital, Finland. Three hundred forty-seven patients (22%) developed advanced disease and 130 STS patients (9%) developed pulmonary metastases as first systemic relapse. Seventy four patients (5%) were operated for lung metastases. RESULTS: Fifty-five patients (42%) had a complete and 19 (15%) incomplete resection. Fifty-six (43%) were unoperated. Median OS after complete or incomplete metastasectomy, chemotherapy, or best supportive care was 22, 18, 8, and 5 months, respectively. Twelve patients (9%) developed no further metastases and are alive with no evidence of disease. Disease-free survival (DFS) for completely resected patients was 17% at 5 years. All long-term survivors had oligometastatic disease and they underwent one to three complete metastasectomies. CONCLUSIONS: Complete pulmonary metastasectomy in STS results in 5 years DFS in nearly one-fifth of patients. Most of these patients are probably cured.

Estrogen receptor beta expression correlates with proliferation in desmoid tumors.

BACKGROUND AND OBJECTIVES: Estrogen receptor signaling and cyclin D1 have a major role in tumor cell proliferation in breast cancer. Desmoid tumors are rare neoplasms that may respond to endocrine treatment. The present study aimed to investigate the expression levels and the clinical relevance of estrogen receptor beta (ERß) and cyclin D1 in desmoid tumors. METHODS: This study consists of 83 patients with a surgically treated desmoid tumor. ERß and cyclin D1 expression was examined by immunohistochemistry in tissue microarrays. Cyclin A and Ki67 were studied in our previous work. RESULTS: Median ERß expression was 10.8%. ERß expression correlated with expression of the proliferation antigens Ki67 (rp = 0.35, P = 0.003), cyclin D1 (rp = 0.34, P = 0.004), and cyclin A (rp = 0.34, P = 0.004). ERß immunoexpression showed a trend towards predictive impact for recurrence as a continuous variable. Further explorative analysis indicated that very high ERß expression was related to high risk of relapse (hazard ratio [HR] 2.6; P = 0.02). Median cyclin D1 expression was 15.6%. High cyclin D1 expression was associated with high Ki67 and cyclin A expression. Cyclin D1 was not associated with time to recurrence. CONCLUSIONS: ERß and cyclin D1 immunopositivity correlated with high proliferation in desmoid tumors. High ERß expression might be predictive for postoperative recurrence.