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Objective: The aim of the study is to assess the effect of perioperative chemo-therapy (CTX) in patients with grade II-III extremity soft tissue sarcoma (eSTS) on overall survival (OS) and evaluate whether the PERSARC prediction tool could identify patients with eSTS more likely to benefit from CTX.Methods: Patients (18-70 years) with primary high-grade eSTS surgically treated with cura-tive intent were included in the retrospective cohort study. The effect of any perioperative CTX and anthracycline + ifosfamide (AI)-based CTX on OS was investigated in three PERSARC-risk groups (high/intermediate/low). The PERSARC-risk groups were defined by the 33% and 66% quantile of the predicted 5-year OS of the study population equal to a 5-year OS of 65.8% and 79.8%, respectively. The effect of CTX on OS was investigated with weighted Kaplan-Meier curves and multivariable Cox models with an interaction between risk group and CTX.Results: This study included 5683 patients. The weighted Kaplan-Meier curves did not demonstrate a beneficial effect of any CTX and AI-based CTX on OS in the overall population. However, in the high PERSARC-risk group the 5-year OS of AI-based CTX was significantly better than no CTX (69.8% vs 59.0%, respectively, p Z 0.004) (HR 0.66, 95% CI 0.53-0.83).Conclusions: This study demonstrated a beneficial effect of AI-based CTX on OS in a selected group of high-risk patients with an absolute survival benefit of 11% as stratified by the PERSARC prediction tool. However, no beneficial effect of CTX on OS was found in the overall population of patients with primary high-grade eSTS younger than 70 years.(c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Background: The majority of gastroinstestinal stromal tumours (GISTs) harbour oncogenic mutations in the gene encoding for the tyrosine kinase (TK) KIT. The most common mutations are found in exon 11, followed by mutations in exon 9. The latter mutations are associated more frequently with GISTs in extra-gastric locations and with a more aggressive clinical behaviour. Summary: Here, we review the unique and often poorly recognized molecular, biological, and clinical characteristics that differentiate KIT exon 9-mutant GISTs from other GIST subtypes. In particular, KIT exon 9 mutations are associated to KIT mutants with retained sensitivity to stimulation by stem cell factor and localization to the cell membrane. Moreover, KIT exon 9-mutant GISTs display significant activation of KIT-independent oncogenic pathways. These characteristics may explain the limited activity of the TK inhibitor imatinib in the adjuvant setting in KIT exon 9-mutant GISTs, as well as their lower sensitivity to standard dose imatinib in the advanced setting. In contrast, the multi-TK inhibitor sunitinib displays better activity in KIT exon 9-mutant GISTs compared to others. Key Messages: KIT exon 9-mutant GISTs represent a subtype of GIST distinct from other GISTs, including the more common KIT exon 11-mutant GISTs. A better understanding of the molecular biology and clinical behaviour of KIT exon 9-mutant GISTs may help identify more improved treatment options.

Over the past 20 years, the management of gastrointestinal stromal tumors has acted as an important model in the advancement of molecularly targeted therapies for solid tumors. The success of imatinib has established it as a lasting therapy in the management of early-stage and advanced disease in the first-line setting. Imatinib resistance inevitably develops, resulting in the need for further lines of therapy. Ripretinib is an orally administered switch-control tyrosine kinase inhibitor, specifically developed to target both primary and secondary KIT and PDGFRα resistance mutations. Herein, the authors discuss the molecular rationale, the preclinical evidence and the clinical use of ripretinib in the treatment of gastrointestinal stromal tumors in the advanced stages of disease.

Surgery is the mainstay of treatment for retroperitoneal sarcoma (RPS), but local recurrence is common. Biologic behavior and recurrence patterns differ significantly among histologic types of RPS, with implications for management. The Transatlantic Australasian RPS Working Group (TARPSWG) published a consensus approach to primary RPS, and to complement this, one for recurrent RPS in 2016. Since then, additional studies have been published, and collaborative discussion is ongoing to address the clinical challenges of local recurrence in RPS.An extensive literature search was performed, and the previous consensus statements for recurrent RPS were updated after review by TARPSWG members. The search included the most common RPS histologic types: liposarcoma, leiomyosarcoma, solitary fibrous tumor, undifferentiated pleomorphic sarcoma, and malignant peripheral nerve sheath tumor.Recurrent RPS management was evaluated from diagnosis to follow-up evaluation. For appropriately selected patients, resection is safe. Nomograms currently are available to help predict outcome after resection. These and other new findings have been combined with expert recommendations to provide 36 statements, each of which is attributed a level of evidence and grade of recommendation. In this updated document, more emphasis is placed on histologic type and clarification of the intent for surgical treatment, either curative or palliative. Overall, the fundamental tenet of optimal care for patients with recurrent RPS remains individualized treatment after multidisciplinary discussion by an experienced team with expertise in RPS.Updated consensus recommendations are provided to help guide decision-making for treatment of locally recurrent RPS and better selection of patients who would potentially benefit from surgery.

STUDY DESIGN: A review of prospectively collected data on a consecutive series of patients undergoing single-stage anterior high sacrectomy for locally recurrent rectal carcinoma (LRRC). OBJECTIVE: To determine the clinical outcome of patients who underwent anterior high sacrectomy for LRRC. SUMMARY OF BACKGROUND DATA: High sacrectomy for oncological resection remains technically challenging. Surgery has the potential to achieve cure in carefully selected patients. Complete (R0) tumor excision in LRRC may require sacrectomy. High sacral resections (S3 and above) typically require a combined anterior/supine and posterior/prone procedure. We investigated our experience performing single-stage anterior high sacrectomy for LRRC. METHODS: A consecutive series of patients with LRRC without systemic metastases who underwent resection with curative intent requiring high sacrectomy were identified. A review of a prospectively maintained colorectal and spine cancer database data was performed. An oblique dome high sacral osteotomy was performed during a single-stage anterior procedure. Outcome measures included surgical resection margin status, hospital length of stay, postoperative complications, physical functioning status, and overall survival. RESULTS: Nineteen consecutive patients were treated between 2002 and 2011. High sacrectomy was performed at sacral level S1-S2 in 4 patients, S2-S3 in 9 patients, and through S3 in 6 patients. An R0 resection margin was achieved histologically in all 19 cases. There was 1 early (

A higher incidence of additional malignancies has been described in patients diagnosed with gastrointestinal stromal tumors (GIST). This study aimed to identify risk factors for developing additional malignancies in patients diagnosed with GIST and evaluate the impact on survival. Individuals diagnosed with GIST from 2001 to2009 were identified from the SEER database. Logistic regression was used to identify predictors of additional malignancies and Cox-proportional hazards regression used to identify predictors of survival. In the study period, 1705 cases of GIST were identified, with 181 (10.6%) patients developing additional malignancies. Colorectal cancer was the most common cancer developing within 6 months of GIST diagnosis (30%). The median time to diagnosis of a malignancy after 6 months of GIST diagnosis was 21.9 months. Older age (p 0.0001) and extraoesophagogastric GIST (p = 0.0027) were significant prognostic factors associated with additional malignancies. The overall 5-year survival was 65%, with the presence of additional malignancies within 6 months of GIST diagnosis associated with poor overall survival (54%, HR 1.55 1.05-2.3 95% CI, p = 0.04). Predictive factors of additional malignancies in patients diagnosed with GIST are increasing age and the primary disease site. Developing additional malignancies within 6 months of GIST diagnosis is associated with poorer overall survival. Targeted surveillance may be warranted in patients diagnosed with GIST that are at high risk of developing additional malignancies.

The objective of this study was to make an assessment of the utility of fine needle aspiration cytology (FNAC), in a "one-stop" symptomatic breast triple assessment clinic. Controversy surrounds the optimal tissue biopsy methodology in the diagnosis of symptomatic breast cancer and the identification of benign disease. FNAC in the context of a Rapid Assessment Breast Clinic (RABC) allows the same day diagnosis and early treatment of breast cancer, with the immediate reassurance and discharge of those with benign disease. We analyzed prospective data accrued at a RABC, over a 4-year period from 2004 to 2007. All patients were triple assessed, with FNACs performed on site by two consultant cytopathologists. Investigations were reported immediately, and clinical data were captured via a database using compulsory data field entry. There were 4487 attendances at our RABC, with 1572 FNACs were performed. The positive predictive value of FNAC with a C5 cancer diagnosis was 100%, 95.6% for a C4 report, with a complete sensitivity of 94%. The full specificity of correctly identified benign lesions was 77.4%, with a false negative rate of 3.85%. This enabled 66% of patients attending the RABC to receive a same day diagnosis of benign disease and discharge. FNAC is highly accurate in the diagnosis of symptomatic breast cancer in an RABC. FNAC allows accurate diagnosis of benign disease and immediate discharge of the majority of patients. In this era, when a large majority of patients have benign disease, we believe that FNAC provides an equivalent, if not better, method of evaluation of patients in a triple assessment RABC.