The clinical outcomes of undifferentiated pleomorphic sarcoma (UPS): A single-centre experience of two decades with the assessment of PD-L1 expressions.

INTRODUCTION: Little is known about undifferentiated pleomorphic sarcoma (UPS) because of the low incidence and heterogeneous diagnosis of sarcoma. We investigated the oncologic outcomes of patients with UPS in a real-practice setting in association with adjuvant treatments and assessment of PD-L1 expression. MATERIALS AND METHODS: We retrospectively reviewed consecutive patients who were diagnosed with UPS in Asan Medical Center between January 1995 and December 2016. PD-L1 staining was performed using formalin-fixed paraffin-embedded tumour tissue by immunohistochemistry, and positive PD-L1 expression was defined as staining in ≥1% of tumour cells. The PD-L1 H-score, which was calculated for statistical analysis as intensity (0-3) multiplied by proportion (0-100), ranged from 0 to 300. RESULTS: Of 205 patients included in our analysis, 176 underwent a curative-intent operation for localised disease. The five-year disease-free survival (DFS) rate of resected UPS patients was 54.3%. Administration of adjuvant therapy did not overcome the poor prognostic factors such as primary tumour size (>5 cm) and locations, especially the abdomen and pelvis. The PD-L1 analysis was available for 114 patients, and 83 (72.8%) showed immunoreactivity for PD-L1 with weak (44/83), intermediate (29/83), and strong (10/83) staining intensities. The positive PD-L1 expression seemed to be associated with prolonged DFS, though no statistical significance was observed. CONCLUSION: Complete surgical resection was the most important UPS treatment strategy, and adjuvant radio- or chemotherapy was insufficient to improve survival. Our results raise the possibility that immunotherapy could be a breakthrough in the treatment of UPS patients.

The Surveillance After Extremity Tumor Surgery (SAFETY) trial: protocol for a pilot study to determine the feasibility of a multi-centre randomised controlled trial.

INTRODUCTION: Following the treatment of patients with soft tissue sarcomas (STS) that are not metastatic at presentation, the high risk for local and systemic disease recurrence necessitates post-treatment surveillance. Systemic recurrence is most often detected in the lungs. The most appropriate surveillance frequency and modality remain unknown and, as such, clinical practice is highly varied. We plan to assess the feasibility of conducting a multi-centre randomised controlled trial (RCT) that will evaluate the effect on overall 5-year survival of two different surveillance frequencies and imaging modalities in patients with STS who undergo surgical excision with curative intent. METHODS AND ANALYSIS: The Surveillance After Extremity Tumor Surgery trial will be a multi-centre 2×2 factorial RCT. Patients with non-metastatic primary Grade II or III STS treated with excision will be allocated to one of four treatment arms1: chest radiograph (CXR) every 3 months for 2 years2; CXR every 6 months for 2 years3; chest CT every 3 months for 2 years or4 chest CT every 6 months for 2 years. The primary outcome of the pilot study is the feasibility of a definitive RCT based on a combination of feasibility endpoints. Secondary outcomes for the pilot study include the primary outcome of the definitive trial (overall survival), patient-reported outcomes on anxiety, satisfaction and quality of life, local recurrence-free survival, metastasis-free survival, treatment-related complications and net healthcare costs related to surveillance. ETHICS AND DISSEMINATION: This trial received provisional ethics approval from the McMaster/Hamilton Health Sciences Research Ethics Board on 7 August 2019 (Project number 7562). Final ethics approval will be obtained prior to commencing patient recruitment. Once feasibility has been established and the definitive protocol is finalised, the study will transition to the definitive study. TRIAL REGISTRATION: NCT03944798; Pre-results.

Individualised risk assessment for local recurrence and distant metastases in a retrospective transatlantic cohort of 687 patients with high-grade soft tissue sarcomas of the extremities: a multistate model.

OBJECTIVES: This study investigates the effect of surgical margins and radiotherapy, in the presence of individual baseline characteristics, on survival in a large population of high-grade soft tissue sarcoma of the extremities using a multistate model. DESIGN: A retrospective multicentre cohort study. SETTING: 4 tertiary referral centres for orthopaedic oncology. PARTICIPANTS: 687 patients with primary, non-disseminated, high-grade sarcoma only, receiving surgical treatment with curative intent between 2000 and 2010 were included. MAIN OUTCOME MEASURES: The risk to progress from 'alive without disease' (ANED) after surgery to 'local recurrence' (LR) or 'distant metastasis (DM)/death'. The effect of surgical margins and (neo)adjuvant radiotherapy on LR and overall survival was evaluated taking patients' and tumour characteristics into account. RESULTS: The multistate model underlined that wide surgical margins and the use of neoadjuvant radiotherapy decreased the risk of LR but have little effect on survival. The main prognostic risk factors for transition ANED to LR are tumour size (HR 1.06; 95% CI 1.01 to 1.11 (size in cm)) and (neo)adjuvant radiotherapy. The HRs for patients treated with adjuvant or no radiotherapy compared with neoadjuvant radiotherapy are equal to 4.36 (95% CI 1.34 to 14.24) and 14.20 (95% CI 4.14 to 48.75), respectively. Surgical resection margins had a protective effect for the occurrence of LR with HRs equal to 0.61 (95% CI 0.33 to 1.12), and 0.16 (95% CI 0.07 to 0.41) for margins between 0 and 2 mm and wider than 2 mm, respectively. For transition ANED to distant metastases/Death, age (HR 1.64 (95% CI 0.95 to 2.85) and 1.90 (95% CI 1.09 to 3.29) for 25-50 years and >50 years, respectively) and tumour size (1.06 (95% CI 1.04 to 1.08)) were prognostic factors. CONCLUSIONS: This paper underlined the alternating effect of surgical margins and the use of neoadjuvant radiotherapy on oncological outcomes between patients with different baseline characteristics. The multistate model incorporates this essential information of a specific patient's history, tumour characteristics and adjuvant treatment modalities and allows a more comprehensive prediction of future events.

The assessment of primitive or metastatic malignant pulmonary tumors in children.

BACKGROUND: The purpose of our study is to assess primitive and secondary malignant pulmonary tumors in children. The presence of lung tumors in newborns and infants is a point of interest to specialists in pediatric surgery, thoracic surgery and genetics due to the high death rate. The 5-years survival rate communicated by EUROCARE-study is less than 10% for primitive tumors and less than 15% in lung metastases. MATERIALS AND METHOD: We performed a retrospective study which analysed 11 children with pulmonary primary ormetastatic tumors admitted in the Pediatric Surgery Department "Prof. Dr. Al. Pesamosca" of the Emergency Clinical Hospital for Children "Maria Sklodowska Curie",Bucharest. The analysed and operated patients underwent surgery by Prof. Dr. Al. Pesamosca and the authors during the period of 1985-2011. In our series there where 4 primitive lung tumors and 7 secondary ones: 8 underwent surgery and 2 died before being operated on. The incidence of primitive pulmonary lung malignancies is higher for females, 3 to1, and secondary ones are more frequent in males, 6 to 1. RESULTS: Patients with primitive pulmonary malignancies were late diagnosed. Their age ranged between 1 to 6 years;3 were operated on, out of which 2 died, and 1 operated still survives. The 7 patients with secondary pulmonary malignancies were late diagnosed, too, probably as a consequence of a late diagnosis of the origin tumor. CONCLUSIONS: Even if all malignancies require an early diagnosis and treatment, this aim regarding malignant lung tumors is still a desideratum animating all practitioners. Primitive tumors are diagnosed presenting the main clinical manifestation abroncho pulmonary infection. Secondary lung malignancies are usually asymptomatic and are diagnosed when monitoring a patient for a malignancy with another origin. Chemotherapy,radiotherapy and surgery of malignant primitive tumors or metastatic ones in children remain unsatisfactory because of the late diagnosis and the limited methods of treatment. Nowadays genetics identified the responsible oncogenes for pulmonary blastic explosion and better results could be obtained by genetic surgery.

Pathologic assessment of radiofrequency ablation of pulmonary metastases.

PURPOSE: To evaluate pathologically the effectiveness of radiofrequency (RF) ablation in the treatment of pulmonary metastases. MATERIALS AND METHODS: Patients with multiple pulmonary metastases scheduled for surgical resection were prospectively enrolled. Patients underwent RF ablation of one percutaneously accessible tumor and within 2-4 weeks underwent surgical resection of the ablated tumor and any additional lesions. Resected tumors all were assessed by routine light microscopy, and selected tumors were assessed by immunohistochemistry with MIB1 and proliferative cell nuclear antigen (PCNA). Relationship of ablation zone to the tumor and viability of the ablated tumors were assessed. RESULTS: Nine patients (four men and five women) 46-76 years of age were included in the study. Four patients had metastatic colorectal carcinoma, and five patients had metastases from soft tissue sarcomas. Ablated tumors ranged from 1.0-3.0 cm in diameter. Each target lesion was completely encompassed by the ablation zone. All tumor tissue within the ablation zone showed characteristic changes of coagulative necrosis with hematoxylin and eosin staining. Tumors showed preservation of MIB1 staining but loss of PCNA protein staining. RF ablation resulted in complete coagulative necrosis of all the pulmonary metastases treated in the study. CONCLUSIONS: Although this series is small, it provides histologic support for RF ablation as an effective treatment for selected pulmonary metastases.

Proximal femoral replacements for metastatic bone disease: financial implications for sarcoma units.

Metastatic pathological fractures of the proximal femur are increasingly treated by endoprosthetic proximal femoral replacement. We report the results and the costs incurred performing these procedures at our supra-regional sarcoma unit. Sixty-two patients underwent 63 proximal femoral replacements for metastatic bone disease over a seven-year period. Breast cancer was the most common primary pathology. One patient underwent a revision procedure for infection. Twenty-two patients suffered dislocations, most commonly those undergoing a conventional arthroplasty articulation. The estimated cost of a proximal femoral replacement is 18,002 pounds at our centre. Less than half of this is reimbursed under Payment by Results. Endoprosthetic replacement of the proximal femur is an effective treatment of metastases, but is poorly reimbursed under current funding arrangements.

Cost-effectiveness of pulmonary resection and systemic chemotherapy in the management of metastatic soft tissue sarcoma: a combined analysis from the University of Texas M. D. Anderson and Memorial Sloan-Kettering Cancer Centers.

BACKGROUND: We sought to determine the cost-effectiveness of different treatment strategies for patients with pulmonary metastases from soft tissue sarcoma. METHODS: We constructed a decision tree to model the outcomes of 4 treatment strategies for patients with pulmonary metastases from soft tissue sarcoma: pulmonary resection, systemic chemotherapy, pulmonary resection and systemic chemotherapy, and no treatment. Data from 1124 patients with pulmonary metastases from soft tissue sarcoma were used to estimate disease-specific survival for pulmonary resection and no treatment. Outcomes of systemic chemotherapy and pulmonary resection and of systemic chemotherapy were estimated by assuming a 12-month improvement in disease-specific survival with chemotherapy; this was done on the basis of the widely held but unproven assumption that chemotherapy provides a survival benefit in patients with metastatic soft tissue sarcoma. Direct costs were examined for a series of patients who underwent protocol-based pulmonary resection or doxorubicin/ifosfamide-based chemotherapy. RESULTS: The mean cost of pulmonary resection was 20,339 dollars per patient; the mean cost of 6 cycles of chemotherapy was 99,033 dollars. Compared with no treatment and assuming a 12-month survival advantage with chemotherapy, the incremental cost-effectiveness ratio was 14,357 dollars per life-year gained for pulmonary resection, 104,210 dollars per life-year gained for systemic chemotherapy, and 51,159 dollars per life-year gained for pulmonary resection and systemic chemotherapy. Compared with pulmonary resection, the incremental cost-effectiveness ratio of pulmonary resection and systemic chemotherapy was 108,036 dollars per life-year gained. Sensitivity analyses showed that certain patient and tumor features, as well as the assumed benefit of chemotherapy, affected cost-effectiveness. CONCLUSIONS: For patients with pulmonary metastases from soft tissue sarcoma who were surgical candidates, pulmonary resection was the most cost-effective treatment strategy evaluated. Even with favorable assumptions regarding its clinical benefit, systemic chemotherapy alone, compared with no treatment, was not a cost-effective treatment strategy for these patients.

Cost-effectiveness of staging computed tomography of the chest in patients with T2 soft tissue sarcomas.

BACKGROUND: Published practice guidelines recommend routine chest computed tomography (CT) scanning as part of the staging evaluation for patients with T2 soft tissue sarcomas (STS), although there is no direct evidence to support this practice. The objective of this study was to determine the yield and cost-effectiveness of routine versus selective chest CT scanning for the staging of patients with T2 STS and to identify any subgroups for whom a more selective approach to chest CT scanning could be considered. METHODS: Six hundred consecutive patients with primary, nonthoracic, T2 (> 5 cm) STS underwent both chest X-ray (CXR) and chest CT scanning to evaluate the presence of pulmonary metastatic disease (M1). The authors constructed a decision tree that modeled the outcomes of diagnostic testing for two hypothetical diagnostic strategies: 1) routine chest CT (rCT) or 2) CXR and selective chest CT (sCT). The yield and cost of each strategy were determined; the incremental cost-effectiveness ratio (ICER) was calculated as the cost per additional patient with pulmonary metastases identified by rCT versus sCT. RESULTS: The yield of rCT was higher than that of sCT (M1 disease identified in 19.2% vs. 16.0% of patients, respectively), but rCT was more costly ($1301 vs. $418 per patient, respectively). The ICER of rCT compared with sCT was $27,594 per patient identified with pulmonary metastasis. The expected yields, costs, and ICERs of the diagnostic strategies varied across patient subgroups based on grade, anatomic site, and tumor size. CONCLUSIONS: For patients with T2 STS, rCT was most cost-effective in patients with high-grade lesions or extremity lesions. The findings of this study do not support the routine use of chest CT scanning in all patients with T2 STS.

Effective follow-up strategies in soft tissue sarcoma.

The value of surveillance for detection of recurrences in patients with soft tissue sarcoma (STS) after definitive surgical resection of the primary tumor is based on the premise that early recognition and treatment of local or distant recurrence can prolong survival. Surveillance strategies should meet the criteria of easy implementation, accuracy, and cost-effectiveness. Although guidelines have been proposed for follow-up of patients with STS, there are few data in the medical literature on the effectiveness of these recommendations. We reviewed the effectiveness of a surveillance program for primary extremity STS in an effort to provide an evidence-based rationale for follow-up of STS. We concluded that clinical assessment of patient symptoms, chest X-ray imaging, and physical examination are effective strategies for follow-up of extremity STS. Chest X-ray imaging also appears to be cost-effective, at least for high-grade extremity STS. Imaging of the primary extremity site by computed tomography (CT) scan or magnetic resonance imaging (MRI) on an annual basis and routine laboratory blood tests were ineffective strategies for recurrence detection. However, certain patient characteristics such as body habitus, previous radiation therapy, and location of the primary tumor site may require the use of CT scans and MRI for adequate clinical assessment. The role of specific surveillance strategies for recurrence detection for sarcomas of the trunk, head and neck, retroperitoneum, and viscera has yet to be defined.

An assessment of prognostic factors in soft-tissue sarcoma of the head and neck.

OBJECTIVE: This study evaluates the outcome, patterns of failure, and prognostic factors in head and neck soft-tissue sarcoma in the adult. DESIGN: A retrospective evaluation of 73 patients treated recently for this rare disease. The minimum follow-up for all patients was 3 years with the living patients having a mean follow-up of 4.6 years. SETTING: All patients were treated between January 1980 and December 1988, at the Princess Margaret Hospital-Ontario Cancer Institute, Toronto, the major sarcoma referral center for a population in excess of 3 million. PATIENTS OR PARTICIPANTS AND INTERVENTIONS: Fifty-two patients were treated with curative intent: 10 by surgery without radiotherapy and 42 with surgery and radiotherapy. Twelve patients received adjuvant chemotherapy. OUTCOME MEASURES: Five-year cause-specific survival, local relapse, and distant failure rates were calculated by the product limit method. Comparisons between survival curves were carried out by the log-rank statistic and Cox regression analysis was performed to assess the influence of prognostic factors. RESULTS: The 5-year cause-specific survival was 62%, with a local relapse rate of 41% and distant relapse rate of 31%. Extension to adjacent structures, high grade, and large lesion size were associated with poorer survival. Gross residual tumor also was associated with high local failure (75% failure) despite the addition of radiation therapy. Those with clear surgical margins or only microscopic involvement fared much more favorably and had similar local control rates (26% and 30% failure, respectively) provided adjuvant radiotherapy was given. However, 68% of patients dying as a result of their sarcoma had uncontrolled local disease because of the high incidence (27%) of gross residuum following surgery in this series. CONCLUSIONS: This series highlights the absolute necessity for resection of all overt disease with planned adjunctive radiotherapy and appropriate reconstruction in most cases. This is achieved more easily in the setting of a specialized sarcoma treatment unit.

Position paper: imaging methods for primary renal tumors of childhood: costs versus benefits.

The patterns of disease distribution at diagnosis and during follow-up were cataloged for the primary renal tumors of childhood. These data, derived from more than 1,500 patients, were used to define the most rewarding and cost-effective imaging methods required for patient management. The basic information needed prior to surgery includes whether there is a functioning kidney on the opposite side, and whether there are lung metastases or inferior vena cava thrombi. Simple X-ray examinations and ultrasonography (US) will provide the necessary data. Postoperatively, when the histology is known, examination of the brain (MRI or CT scan) is needed for patients with the rhabdoid tumor and clear cell sarcoma of the kidney (CCSK) who are prone to develop brain lesions; and the skeletal system (bone scan, X-ray skeletal survey) for CCSK and for renal cell carcinoma patients who tend to develop bone metastases. Continuing examination of the lung (chest films) is required for all histologies except perhaps for mesoblastic nephroma, which seldom metastasizes. The opposite kidney needs follow-up (US) for 5 or more years to exclude metachronous involvement if nephrogenic rests are present in either kidney. Sophisticated imaging studies, which cost five times or more than simple X-ray examinations or US, are not warranted routinely, and should be reserved for those cases where simpler, less expensive studies do not suffice for reaching patient management decisions.

Computed tomographic assessment of adrenal masses.

Clinical and biochemical information together with good spatial resolution by CT offers final assessment of certain adrenal masses even when their size is 1-2 cm. Moderate sized tumours, i.e. up to 8 cm in size are amenable to accurate definition by CT. In some situations it is the final diagnostic modality of adrenal tumours. Tumour recurrence or deposition in the adrenal area is accurately followed by performing sequential scans. Extension and dissemination of neoplasms beyond the confines of the suprarenal can now be defined more readily by CT. Lipid and blood content of adrenal tumours gives low density areas which can mistakenly be assessed as 'cystic' lesions. Large tumours in the area frequently require additional clinical, biochemical and radiological investigation before diagnostic solution is achieved.