Mann Hong Tan

The influence of primary site on outcomes in leiomyosarcoma: a review of clinicopathologic differences between uterine and extrauterine disease.

Background: Leiomyosarcomas (LMS) comprise 25% of soft tissue sarcomas. Recent reports suggest differences in treatment outcomes between uterine (uLMS) and extrauterine (eLMS) disease that may reflect distinct disease biologies. We sought to identify prognostic factors in LMS and clinicopathologic differences between uLMS and eLMS. Methods: This is a single-center retrospective study evaluating 97 eligible patients treated for LMS between 2002 and 2010. Results: Median follow-up was 21.2 months. uLMS affected 53% of patients, and was less common beyond age 60 years compared with eLMS (10% vs. 37%, P=0.002). Seventy-two percent of patients presented with nonmetastatic disease. Of these, 94% underwent curative surgery, among whom more uLMS patients achieved negative surgical margins (90% vs. 45%, P=0.003). There were no significant differences in adjuvant therapy use and relapse patterns between uLMS and eLMS. Half of metastatic patients received palliative chemotherapy, among whom 76% received anthracycline-based chemotherapy in first line to which response rate was 31%. Median overall survival was 45.2 months, 49.8 months in uLMS, and 40.5 months in eLMS (P=0.294). Among patients without metastases, median survival was 60.8 months (77.3 vs. 48.1 mo in uLMS and eLMS, respectively, P=0.194). In metastatic disease, median survival was 20.7 months (22.0 vs. 17.5 mo in uLMS and eLMS, respectively, P=0.936). Advanced disease stage, bone metastases and lack of metastasectomy prognosticated for inferior survival. Conclusions: While demonstrating interesting clinicopathologic differences, the evidence for uLMS and eLMS being biologically distinct remains inconclusive. Disease stage is prognostically most important in LMS.

Germline Mutations in Cancer Predisposition Genes are Frequent in Sporadic Sarcomas.

Associations of sarcoma with inherited cancer syndromes implicate genetic predisposition in sarcoma development. However, due to the apparently sporadic nature of sarcomas, little attention has been paid to the role genetic susceptibility in sporadic sarcoma. To address this, we performed targeted-genomic sequencing to investigate the prevalence of germline mutations in known cancer-associated genes within an Asian cohort of sporadic sarcoma patients younger than 50 years old. We observed 13.6% (n = 9) amongst 66 patients harbour at least one predicted pathogenic germline mutation in 10 cancer-associated genes including ATM, BRCA2, ERCC4, FANCC, FANCE, FANCI, MSH6, POLE, SDHA and TP53. The most frequently affected genes are involved in the DNA damage repair pathway, with a germline mutation prevalence of 10.6%. Our findings suggests that genetic predisposition plays a larger role than expected in our Asian cohort of sporadic sarcoma, therefore clinicians should be aware of the possibility that young sarcoma patients may be carriers of inherited mutations in cancer genes and should be considered for genetic testing, regardless of family history. The prevalence of germline mutations in DNA damage repair genes imply that therapeutic strategies exploiting the vulnerabilities resulting from impaired DNA repair may be promising areas for translational research.

Critical evaluation of contemporary management in a new Pelvic Exenteration Unit: The first 25 consecutive cases

AIM To critically appraise short-term outcomes in patients treated in a new Pelvic Exenteration (PE) Unit. METHODS This retrospective observational study was conducted by analysing prospectively collected data for the first 25 patients (16 males, 9 females) who underwent PE for advanced pelvic tumours in our PE Unit between January 2012 and October 2016. Data evaluated included age, co-morbidities, American Society of Anesthesiologists (ASA) score, Eastern Cooperative Oncology Group (ECOG) status, preoperative adjuvant treatment, intra-operative blood loss, procedural duration, perioperative adverse event, lengths of intensive care unit (ICU) stay and hospital stay, and oncological outcome. Quantitative data were summarized as percentage or median and range, and statistically assessed by the χ2 test or Fisher’s exact test, as applicable. RESULTS All 25 patients received comprehensive preoperative assessment via our dedicated multidisciplinary team approach. Long-course neoadjuvant chemoradiotherapy was provided, if indicated. The median age of the patients was 61.9-year-old. The median ASA and ECOG scores were 2 and 0, respectively. The indications for PE were locally invasive rectal adenocarcinoma (n = 13), advanced colonic adenocarcinoma (n = 5), recurrent cervical carcinoma (n = 3) and malignant sacral chordoma (n = 3). The procedures comprised 10 total PEs, 4 anterior PEs, 7 posterior PEs and 4 isolated lateral PEs. The median follow-up period was 17.6 mo. The median operative time was 11.5 h. The median volume of blood loss was 3306 mL, and the median volume of red cell transfusion was 1475 mL. The median lengths of ICU stay and of hospital stay were 1 d and 21 d, respectively. There was no case of mortality related to surgery. There were a total of 20 surgical morbidities, which occurred in 12 patients. The majority of the complications were grade 2 Clavien-Dindo. Only 2 patients experienced grade 3 Clavien-Dindo complications, and both required procedural interventions. One patient experienced grade 4a Clavien-Dindo complication, requiring temporary renal dialysis without long-term disability. The R0 resection rate was 64%. There were 7 post-exenteration recurrences during the follow-up period. No statistically significant relationship was found among histological origin of tumour, microscopic resection margin status and postoperative recurrence (P = 0.67). Four patients died from sequelae of recurrent disease during follow-up. CONCLUSION By utilizing modern assessment and surgical techniques, our PE Unit can manage complex pelvic cancers with acceptable morbidities, zero-rate mortality and equivalent oncologic outcomes.

Atypical Presentation of High-Grade Intramedullary Osteosarcoma with Bilateral Cervical, Supraclavicular, and Axillary Lymphadenopathy: A Case Report and Literature Review

Osteosarcoma typically presents with primary site pain. The authors report a case of extensive metastatic osteosarcoma without any complaint of primary site pain during initial presentation. The 23-year-old female patient presented with simultaneous multiple cervical, supraclavicular, and axillary lymphadenopathy, as well as two large subcutaneous fat tumours. Despite initial excision biopsy of cervical lymph nodes, the diagnosis of osteosarcoma was only clinched after open biopsy of the right distal femur lesions and further histological evaluation. Though the patient was promptly started on neo-adjuvant chemotherapy and achieved excellent histological response to treatment, the disease had relapsed quickly and she succumbed to the disease one year after initial presentation. This report highlights the need to be vigilant in the workup and investigation of osteosarcoma, as the presenting symptoms may be more heterogenous than the conventional teaching of primary site pain.

Treatment and outcomes of melanoma in Asia: Results from the National Cancer Centre Singapore.

Acral melanoma (AM) and mucosal melanoma (MM) make up more than half of melanomas in Asia but comprise only 5% of cases in Caucasians, where cutaneous melanoma (CM) predominates. AM and MM are thought to be genetically and biologically distinct from CM. We report the characteristics and outcomes of melanoma patients from the National Cancer Centre Singapore.

205 INVITED Biomechanics Based Microfluidic Biochip for the Label-free Isolation and Retrieval of Circulating Tumour Cells

Immunomagnetic separation methodologies are currently the gold standard for circulating tumour cells (CTCs) isolation but face various drawbacks such as complex sample preparation and biomarker specificity. We developed a label-free biomechanics based microfluidic biochip that is capable of physically isolating and retrieving rare viable CTCs from cancer patient’s blood. The principle is simple and makes use of the fact that cancer cells have biomechanical properties that are significantly different from that of blood cells. The key innovation lies in the unique crescentshape microstructures which form the cell traps within the biochip. Instead of using biomarkers, these cell traps gently ‘filters’ CTCs from other blood components based on the biomechanical property differences between red blood cells, white blood cells and CTCs. Following this, the CTCs caught in these traps can then be retrieved in their wholly intact and viable state. Here, no sample pre-preparation of whole blood and antibodies is required. Blood collected in an EDTA tube can be processed straightaway in this biochip. Clinical blood samples from metastatic patients further verifies the applicability of the technique. Also, results from clinical tests showed that not all CTCs isolated were tested positive for EpCAM or CK. In fact, the CTCs were observed to be heterogeneous not only in terms of morphology such as cell size but also expression of EpCAM or CK. Significant number of CTCs where found to be EpCAM(−) or CK(−), CD45(−) but DAPI(+). This indicates that there are subpopulations of CTCs that warrants further investigation.