What is the association of preoperative biopsy with recurrence and survival in retroperitoneal sarcoma? A systematic review by the Australia and New Zealand Sarcoma Association clinical practice guidelines working party.

Preoperative biopsy for retroperitoneal sarcoma (RPS) enables appropriate multidisciplinary treatment planning. A systematic review of literature from 1990 to June 2022 was conducted using the population, intervention, comparison and outcome model to evaluate the local recurrence and overall survival of preoperative biopsy compared to those that had not. Of 3192 studies screened, five retrospective cohort studies were identified. Three reported on biopsy needle tract seeding, with only one study reporting biopsy site recurrence of 2 %. Two found no significant difference in local recurrence and one found higher 5-year local recurrence rates in those who had not been biopsied. Three studies reported overall survival, including one with propensity matching, did not show a difference in overall survival. In conclusion, preoperative core needle biopsy of RPS is not associated with increased local recurrence or adverse survival outcomes.

A systematic review of the role of chemotherapy in retroperitoneal sarcoma by the Australia and New Zealand sarcoma association clinical practice guidelines working party.

BACKGROUND: In primary localised resectable retroperitoneal sarcoma (RPS), loco-regional and distant relapse occur frequently despite optimal surgical management. The role of chemotherapy in improving outcomes is unclear. METHODS: A systematic review was conducted, using the population, intervention, comparison outcome (PICO) model, to evaluate whether neoadjuvant or adjuvant chemotherapy improve outcomes in adults with primary localised resectable RPS. Medline, Embase and Cochrane Central were queried for publications from 1946 to June 2022 that evaluated recurrence free survival, overall survival, and post operative complications. Each study was screened by two independent reviewers for suitability. A qualitative synthesis of the results was performed. RESULTS: Twenty three studies were identified; one meta-analysis of retrospective studies and 22 retrospective studies including three with propensity matched cohorts. Most studies did not analyse outcomes by histology, detail treatment regimens, provide baseline characteristics or selection criteria for those receiving chemotherapy. Evidence of selection bias was illustrated in several studies. Newcastle-Ottawa quality of retrospective cohort studies was good for 12 studies and poor for 10 studies. All studies were assessed as Level III-2 evidence by the Australian NHMRC hierarchy. Overall, the addition of neoadjuvant or adjuvant chemotherapy to surgery was not associated with improvement in local recurrence, metastasis free survival, disease free survival or overall survival in primary localised resectable RPS. There is some evidence of an association of chemotherapy with worse overall survival. One single centre study showed that neoadjuvant chemotherapy was not associated with increased post operative complications compared to surgery alone in primary localised resectable RPS. CONCLUSIONS: There is currently no evidence that demonstrates the addition of chemotherapy to surgery improves outcomes in adult patients with primary localised resectable RPS. Available evidence is limited by its retrospective nature and high likelihood of selection bias with chemotherapy generally administered to patients at higher risk of recurrence and many patients not receiving care in high volume sarcoma centres. Randomised trials are required to conclusively determine the role of chemotherapy in primary localised resectable RPS.

The role of radiation therapy in the management of primary retroperitoneal sarcoma: A systematic review and clinical practice guidelines from the Australia and New Zealand Sarcoma Association.

While surgery is the mainstay of treatment for localised retroperitoneal sarcoma, the use of radiotherapy (RT) remains controversial. This systematic review aimed to evaluate the role of RT for retroperitoneal sarcoma. A systematic review using the population, intervention, comparison, and outcome model from 1990 to 2022 identified 66 studies (a mixture of preoperative and postoperative RT); one randomised controlled trial (RCT) with two publications, 18 registry studies, and 46 retrospective studies. In the RCT of preoperative RT, there was no difference in local/abdominal recurrence. The pooled analysis of this RCT and a retrospective study showed a significant abdominal recurrence free survival benefit with preoperative RT in low grade liposarcoma. The RCT and the majority of retrospective series found RT did not improve recurrence free survival (11 of 16 no difference in combined local and distant RFS, 11 of 13 no difference in distant metastasis free survival), disease specific survival (9 of 12 studies) or overall survival (33 of 49 studies). The majority of studies found no association between RT and perioperative morbidity. In summary, preoperative RT may improve local control for low grade (well-differentiated or grades 1-2 dedifferentiated) liposarcoma, but not other histological subtypes. There is no strong evidence that perioperative RT provides an overall survival benefit. Patients with low grade retroperitoneal liposarcoma can be considered for preoperative RT to improve abdominal recurrence free survival. The rationale and level of evidence in this scenario should be carefully discussed by the multidisciplinary team with patients. RT should not be routinely recommended for other histological subtypes.

Association of chemotherapy dose intensity and age with outcomes in patients with Ewing's family sarcoma.

BACKGROUND: Ewing's family sarcoma (EFS) is an aggressive malignancy with a peak incidence in adolescents. Multimodal treatment involves surgery and/or radiotherapy, and chemotherapy typically with VDC/IE (vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide). There is a paucity of data for the treatment of adults, with protocols extrapolated from the pediatric setting. This study aimed to assess patterns of care, chemotherapy tolerability across age groups, and outcomes from four Australian sarcoma centers. METHODS: ANZSA ACCORD sarcoma database and medical records were used to identify and collect data of patients aged ≥ 10 years with EFS who received VDC/IE between 2010 and 2020. Survival outcomes were analyzed based on chemotherapy received dose intensity (RDI). Clinical predictors of RDI were explored using logistic regression. RESULTS: Of 146 patients with EFS, 76 received VDC/IE. The majority had localized disease (65%). Seventy-one percent completed scheduled chemotherapy, with some requiring dose reduction (29%), delay > 7 days (65%), or cycle omission (4%). Hematological toxicity was the main reason for dose reduction/delay. Fifty-seven percent patients achieved an acceptable RDI ≥85%. Compared to those aged 10-19, the odds ratio for acceptable RDI aged 40-59 was 0.20 (95% CI 0.04-0.86, p = 0.04). RDI was an independent prognostic factor for overall survival, after accounting for age, gender, Ewing's type, primary site, and stage (adjusted HR 0.25 [95% CI 0.10-0.63], p = 0.004). CONCLUSION: Survival outcomes in EFS were associated with chemotherapy RDI. Older adults more commonly required dose reduction or early cessation of treatment due to toxicity. VDC/IE chemotherapy should be carefully tailored in adults > 40 years.