What is the role of prognostic factors in management of BSTTs?

From Cancer Guidelines Wiki

Introduction

Current staging systems may not consider sufficient variables to predict outcome, and as sarcoma is a rare tumour it is unlikely that many clinicians or even centres will accumulate enough experience to reliably predict the prognosis of individual patients. Fortunately, some institutions have been able to analyse large series of patients and identify factors associated with prognosis.[1][2][3][4][5][6][7][8][9] At present most reports are generated from the analysis of patients who have undergone surgical resection. Some studies report the factors influencing prognosis after local or distant recurrence.[10][11][5][12][13] Prognostic algorithms and nomograms (graphical representations of probabilities based on multiple variables) are therefore important for multidisciplinary teams managing patients with sarcoma. Not only do these tools allow prediction of prognosis, they inform the need for adjuvant therapies and allow stratification of risk for consideration of entry into clinical trials.[14][6]

Sarcoma Subtypes

Due to the many tumour subtypes and locations it is unlikely that any institution or group will be able to provide a comprehensive assessment of the relevant prognostic factors for all sarcoma subtypes. As a result published reports consider either several tumour types and/or sites grouped together or a single tumour type or site.[15][8][9] Unfortunately, reports often contain small numbers of patients, treated with heterogeneous protocols. The studies vary widely in methodology and quality. Single-institution studies may also lack generalisability. In particular, institutions may treat patients within certain age ranges or of certain ethnicity. Published series focus on groups of patients with osteosarcoma, Ewing’s family tumours and soft tissue sarcoma (STS).

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Osteosarcoma

Osteosarcoma is the most common bone sarcoma with an incidence of approximately three per million. It has been one of the success stories of cancer therapy as over the past forty years survival has improved from 15% to over 70%. This is likely to be the result of advances in systemic therapy.[16][17][18][19] Surgical treatments have also evolved so that limb-sparing surgery is now possible in around 90%. The most recent review of prognostic factors was able to identify only seven papers with sufficient data or statistical analysis to allow re-examination. The authors concluded that response to chemotherapy is an independent prognostic factor, a poor response increasing the risk for dying of the disease possibly approximately 2.4 times. Several other factors may have some prognostic importance but their value is difficult to calculate. These include tumour size, excision margin, ablative surgery, age, male sex, serum alkaline phosphatase level, local recurrence, p-glycoprotein expression, and Erb2 expression.[20]

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Ewing’s Sarcoma Family tumours

Ewing’s sarcoma family tumours are a group of histologically similar small round blue cell tumours that share common chromosomal translocations, most commonly t(11;22) resulting in a fusion gene involving EWS and FLI1. The group contains Ewing’s sarcoma of bone, Askin’s tumour (a characteristic Primitive Neuroectodermal Tumour (PNET) arising in the thorax) and soft tissue Ewing’s or PNET. Rhabdomyosarcoma is typically a childhood cancer which shares with Ewing’s family tumours the appearance of small round blue cells but has immunohistochemical features of skeletal muscle. Approximately 80% of this family of tumours occur in patients under twenty years of age.[21] All of these tumours are rare and Ewing’s tumours of bone make up approximately 3% of all paediatric malignancies.[22][23][24][25]

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Soft tissue sarcoma

As there are around fifty subtypes of STS it is unlikely that prognostic factors will be able to be determined for each type. Historically, most series group soft-tissue sarcoma subtypes and report outcomes based on tumour site. However, as datasets have increased there are more tumour type-specific reports of outcomes.[26][15][27][13][6][8]

Extremity tumours

The limbs (and limb girdles) are the main site of sarcomas. The preservation of limb function is a major focus of treating teams. It appears different factors affect local and distant recurrence.

Trunk tumours

Approximately 20% of sarcomas are located in the trunk. Studies may include visceral tumours in this group but generally retroperitoneal tumours are excluded. Low-grade lesions such as dermatofibrosarcoma protuberans (DFSP) and desmoids are usually excluded from reports of prognosis.

Retroperitoneum

The retroperitoneum is the site of approximately 15-20% of sarcomas. Operability has long been considered the major determinant of outcome.[28][29][30] To date adjuvant therapies have shown little benefit.

Head and Neck

The head and neck are the sites of between 5% and 15% of sarcomas. Due to the presence of vital structures radical resections are difficult or impossible.

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Evidence summary and recommendations

Evidence summary Level References
Predictive models and nomograms have been developed by the analysis of outcomes of large series of patients. These may be used to counsel patients and to identify their need for adjuvant therapies. IV [2], [14], [31], [32], [33], [34], [35], [36], [37], [6], [38], [7], [8]
The improvement in outcome of patients with osteosarcoma is largely due to the inclusion of systemic chemotherapy into the treatment regimen. Tumour response to chemotherapy appears to be the most potent predictor of survival. Tumours situated in the distal limb are associated with improved survival rates. IV [32], [20], [39], [16], [18], [17], [40], [19]
The improvement in outcome of patients with Ewing’s family/PNET is largely due to the inclusion of systemic chemotherapy into the treatment regimen. Tumour response to chemotherapy appears to be a potent predictor of survival. Tumour volume is also a significant predictor of outcome so earlier diagnosis is likely to be helpful. The prognostic factors for patients with skeletal and extra-osseous Ewing’s tumours are similar. IV [41], [42], [43], [44], [22], [45], [21], [24], [23], [25]
Until recently it was uncommon for a single sub-type of soft-tissue sarcoma to have been studied sufficiently to provide reliable prognostic information. Instead most authors report prognostic variables for patients with tumours grouped by site. There are now several case series reporting prognostic information for specific tumour sub-types. IV [33], [46], [14], [31], [2], [47], [11], [48], [10], [49], [50], [51], [52], [8]
For extremity tumours, tumour grade, excision margins and patient age influence rates of local recurrence. Tumour grade, size and depth influence distant recurrence and death. The use of radiotherapy may improve local control. Outcomes may be better when patients are treated in specialised centres. IV [31], [53], [33], [54], [34], [48], [35], [32], [55], [56], [36], [57], [51], [58], [52], [59]
For truncal tumours, tumour grade, excision margins, tumour size and the use of radiotherapy influence local and distant recurrence. IV [31], [30], [60], [35], [61], [38], [46]
Retroperitoneal tumour site confers a worse prognosis for most tumour types. Tumour grade and excision margins influence survival. High-grade histology may be associated with a five-fold increase in death.

As yet there is no evidence that pre-operative therapies improve disease-specific survival. There is some evidence that only tumour grade remains a significant prognostic factor one year after diagnosis.

IV [15], [6], [28], [31], [30], [62], [2], [14], [1], [47], [63], [64], [65], [66], [67], [68], [69], [70], [29], [9]
For tumours of the head and neck, excision margins influence local recurrence. Tumour grade, patient age and the development of local recurrence influence overall survival. IV [71], [72], [73], [74], [75], [76], [77], [78], [73], [79], [80], [81], [82], [83]
Recent publications have examined the role biochemical and haematological markers may play in predicting prognosis. Modifications to current staging systems may be required to accommodate contemporary staging methods. IV [84], [19], [85], [86], [87], [7]
Evidence-based recommendationQuestion mark transparent.png Grade
Statistical models assessing the influence of prognostic factors can be used to counsel patients and to stratify their need for adjuvant therapies or entry into clinical trials.
D


Practice pointQuestion mark transparent.png

Accurate data collection will facilitate further study in this area. Tissue banking will allow further assessment of tumours as new diagnostic and therapeutic modalities emerge.

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Issues requiring more clinical research study

  • Can prognosis be estimated from percutaneous biopsies?
  • Is it possible to identify optimal treatment sequencing from percutaneous biopsies?

References

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