Characterising the immune microenvironment in liposarcoma, its impact on prognosis and the impact of radiotherapy.

BACKGROUND AND OBJECTIVES: Limited literature exists examining the immune microenvironment in liposarcoma, particularly with regard to the impact of radiotherapy. A major problem is the lack of scoring system for the tumour-infiltrating lymphocytes (TILs) in sarcoma. This study aims to describe the immune environment pre- and postradiotherapy and identify the optimal immune infiltrate scoring system for sarcoma. METHODS: Thirty-nine paired tissue samples (pre- and postradiotherapy) from patients with liposarcoma were scored by two pathologists for TILs using pre-existing systems (for breast cancer and melanoma) and compared for interobserver reliability. Immunohistochemical staining was performed for various immune markers. RESULTS: The TIL scoring system for breast cancer yielded perfect agreement (κ = 1.000). 21% of patients had increased TILs after radiotherapy, 87.5% of whom had dedifferentiated liposarcoma. Immune suppressor expression was increased frequently after radiotherapy (CD68 increased in 59.4%, PD-L1 increased in 25%). Immune effector expression (CD8) was unchanged in 84.4%. CONCLUSIONS: Breast cancer TIL scoring is reproducible in liposarcoma and has high interobserver reliability. Radiotherapy was observed to have a limited impact on immune effectors but seemed to have more impact in upregulating immune suppressors, suggesting radiotherapy may contribute to disease control through immunomodulatory effects. Dedifferentiated liposarcoma represents a uniquely responsive subtype.

SPAR - a randomised, placebo-controlled phase II trial of simvastatin in addition to standard chemotherapy and radiation in preoperative treatment for rectal cancer: an AGITG clinical trial.

BACKGROUND: Retrospective studies show improved outcomes in colorectal cancer patients if taking statins, including overall survival, pathological response of rectal cancer to preoperative chemoradiotherapy (pCRT), and reduced acute and late toxicities of pelvic radiation. Major tumour regression following pCRT has strong prognostic significance and can be assessed in vivo using MRI-based tumour regression grading (mrTRG) or after surgery using pathological TRG (pathTRG). METHODS: A double-blind phase 2 trial will randomise 222 patients planned to receive long-course fluoropyrimidine-based pCRT for rectal adenocarcinoma at 18+ sites in New Zealand and Australia. Patients will receive simvastatin 40 mg or placebo daily for 90 days starting 1 week prior to standard pCRT. Pelvic MRI 6 weeks after pCRT will assess mrTRG grading prior to surgery. The primary objective is rates of favourable (grades 1-2) mrTRG following pCRT with simvastatin compared to placebo, considering mrTRG in 4 ordered categories (1, 2, 3, 4-5). Secondary objectives include comparison of: rates of favourable pathTRG in resected tumours; incidence of toxicity; compliance with intended pCRT and trial medication; proportion of patients undergoing surgical resection; cancer outcomes and pathological scores for radiation colitis. Tertiary objectives include: association between mrTRG and pathTRG grouping; inter-observer agreement on mrTRG scoring and pathTRG scoring; studies of T-cell infiltrates in diagnostic biopsies and irradiated resected normal and malignant tissue; and the effect of simvastatin on markers of systemic inflammation (modified Glasgow prognostic score and the neutrophil-lymphocyte ratio). Trial recruitment commenced April 2018. DISCUSSION: When completed this study will be able to observe meaningful differences in measurable tumour outcome parameters and/or toxicity from simvastatin. A positive result will require a larger RCT to confirm and validate the merit of statins in the preoperative management of rectal cancer. Such a finding could also lead to studies of statins in conjunction with chemoradiation in a range of other malignancies, as well as further exploration of possible mechanisms of action and interaction of statins with both radiation and chemotherapy. The translational substudies undertaken with this trial will provisionally explore some of these possible mechanisms, and the tissue and data can be made available for further investigations. TRIAL REGISTRATION: ANZ Clinical Trials Register ACTRN12617001087347. (www.anzctr.org.au, registered 26/7/2017) Protocol Version: 1.1 (June 2017).

Accuracy of computed tomography guided core needle biopsy of musculoskeletal tumours.

BACKGROUND: The accurate diagnosis of musculoskeletal tumours is important for successful treatment. Image guided biopsy is gaining increasing acceptance for obtaining tissue for diagnosis. The aim of the present study is to assess the accuracy of computed tomography (CT)-guided core needle biopsy of musculoskeletal tumours. METHODS: This is a retrospective study on a series of 127 patients with a musculoskeletal tumour. The biopsies were performed over a 4-year period from 1998 to 2001. The accuracy of the CT-guided core needle biopsy was determined by comparing the histology of the biopsy with the final histology of the specimen obtained at open biopsy or surgical resection of the tumour. The effective accuracy was determined by the accuracy of the biopsy to distinguish between a benign and malignant tumour. RESULTS: Computed tomography guided core needle biopsy in the present series has an overall accuracy of 80.3%. The effective accuracy as determined by a malignant versus benign lesion was 89%. There were 86 malignant tumours with a biopsy accuracy of 81.4% and there were 41 benign tumours with a biopsy accuracy of 78%. The positive predictive value (PPV) of a malignant tumour is 98.9% and the PPV of benign tumour 90.2%. The most common site of biopsy was from the femur and thigh, together accounting for 39.4% of the tumours. The most common tumours in this series were liposarcoma (n = 12), osteosarcoma (n = 11) and giant cell tumour (n = 11). There were no reported complications arising from the biopsy. CONCLUSION: Computed tomography guided core needle biopsy is a safe and effective procedure that is important in the diagnosis and management of musculoskeletal tumours. It should be performed in a specialized institution with a multidisciplinary musculoskeletal tumour team.