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We analyzed the prognostic factors for treatment outcomes amongst 34 patients with adult Burkitt lymphoma (BL) who received rituximab with standard first-line chemotherapy. Seven patients had human immunodeficiency virus (HIV)-associated BL. Overall, we observed a complete remission (CR) rate of 91.2%, and 10-year progression-free survival (PFS) and overall survival (OS) was 84.8 and 88.2%, respectively. In patients with concomitant HIV, the prognosis was not different with 10-year PFS of 100% and OS of 88.2%. The majority (71.4%) of HIV-associated BL patients received dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) and had excellent outcomes with 100% CR and no relapses. Central nervous system (CNS) disease, bone marrow involvement and elevated serum lactate dehydrogenase (LDH) levels more than 3 times upper limit of normal (ULN) were associated with poorer survival outcomes. Patients with refractory disease, whilst uncommon (

Background: Mantle cell lymphoma (MCL) is widely considered an incurable malignancy even with current therapies and relapsed/refractory (R/R) disease to primary treatment remains common. With improved treatment guidelines and the advent of novel agents, patients are increasingly being treated with more lines of regimens. However, outcomes after each line of treatment remain poorly characterized, especially in the Asian population. In this paper, we described the survival outcomes in a group of R/R MCL patients. Methods: We retrospectively studied 35 patients with R/R MCL between 1998 and 2020 at the National Cancer Centre Singapore. Patients were followed longitudinally throughout their disease course. Overall survival (OS) and progression-free survival (PFS) were determined by the Kaplan-Meier method. Results: The median OS and PFS from diagnosis were 105 and 40 months, respectively. After first relapse, the median OS and PFS were 52 and 19 months, post-second relapse 32 and 8 months, and post-third relapse 12 and 6 months, respectively. Patients older than 65 years at first relapse had shorter survival (median OS: 22 vs. 55 months, P = 0.0417; median PFS: 9 vs. 29 months, P = 0.001). Early treatment failure after first line therapy was also associated with worse survival outcomes (median OS: 13 vs. 55 months, P < 0.001; median PFS: 9 vs. 26 months, P < 0.001). Conclusion: With each relapse, survival outcomes for patients with MCL are worse. Novel treatment and contemporary outcomes of R/R MCL are encouraging and support the need for continued research in this area. J Hematol. 2021;10(4):187-195 doi: https://doi.org/10.14740/jh890

Background Postintensive care syndrome (PICS) has been identified in a large proportion of medical intensive care unit survivors; however, the occurrence surgical intensive care unit (SICU) survivors is unknown. We implemented a multidisciplinary critical care outpatient clinic (CCOC) to identify the occurrence of PICS in SICU survivors. Methods Seventy acute care surgery and trauma patients, 18 years or older, who remained in the SICU for 72 hours or longer at a Level I trauma center were seen in CCOC at 2 weeks, 12 weeks, and 24 weeks after hospital discharge. The CCOC staffing included a nurse coordinator, social worker, critical care pharmacist, physical therapist, and acute care surgeon who identified PICS sequelae in their respective specialties by clinical criteria and screening questionnaires. Results Of 82 eligible patients, 70 (85.4%) were seen at least once for 116 total visits. Forty-three (61.4%) patients suffered traumatic injuries and 27 (38.6%) underwent emergent general surgery. Sixty-seven (95.7%) demonstrated at least one PICS criterion. Over all visits, 26 (37.1%) patients presented with one PICS criterion, 24 (34.3%) patients with two, and 17 (24.3%) with three. Cognitive impairment was observed in 29 (41.4%) patients, psychiatric in 30 (42.9%), and physical symptoms in 65 (92.9%). Activity Measure for Post-Acute Care scores improved from severe impairment at admission to full function by 12 weeks postdischarge, yet 6 Minute Walk Test scores remained below age-matched references through all visits. Patients expressed mild to moderate depression based on Patient Health Questionnaire-9 scores. A medication reconciliation was completed at 96.5% (112/116) of the visits with 116 total medication recommendations. By 24 weeks following discharge, only 26.4% (14/53) of previously employed patients had resumed work. Conclusion Through the successful implementation of a multidisciplinary CCOC, this study identifies an exorbitant rate of PICS among SICU survivors. Level of evidence Therapeutic/epidemiological, level III.

Study objective To evaluate a surveillance protocol in managing the risk of hepatitis B virus (HBV) reactivation among lymphoma patients with resolved HBV infection receiving rituximab. Design Prospective, single-arm study. Setting National Cancer Centre, Singapore. Patients Lymphoma patients with resolved HBV infection and scheduled to receive rituximab-based treatment. Intervention Close monitoring of HBV DNA levels, ie. every 4-6 weeks during rituximab treatment, every 6-8 weeks in the first year post-treatment, and every 3-4 months in the second year post-treatment. Measurements The efficacy of the surveillance protocol was examined by evaluating the rates of reactivation-related events. Feasibility was evaluated based on patient adherence. An economic analysis using a cost-minimization approach was conducted to compare the costs between the surveillance protocol and universal prophylaxis with entecavir 0.5 mg daily up to 1 year after cessation of rituximab. Main results A total of 66 patients provided analyzable data with a follow-up period of 966.6 months. No hepatitis flare or reactivation-related events were detected. The median adherence rate to the surveillance protocol was 90.5%. Cost savings of US$946.40 per patient over the entire surveillance period were achieved if the surveillance protocol was adopted and was most affected by changes in prophylaxis duration and the cost of antiviral prophylaxis. Conclusions The surveillance protocol is an effective, feasible and cost-saving strategy to manage HBV reactivation among lymphoma patients with resolved HBV infection receiving rituximab.

Worldwide advances in treatment and supportive care for children and adolescents with cancer have resulted in a increasing population of survivors growing into adulthood. Yet, this population is at very high risk of late occurring health problems, including significant morbidity and early mortality. Unique barriers to high-quality care for this group include knowledge gaps among both providers and survivors as well as fragmented health-care delivery during the transition from paediatric to adult care settings. Survivors of childhood and adolescent cancer are at risk for a range of late-occuring side-effects from treatment, including cardiac, endocrine, pulmonary, fertility, renal, psychological, cognitive, and socio-developmental impairments. Care coordination and transition to adult care are substantial challenges, but can be empowering for survivors and improve outcomes, and could be facilitated by clear, effective communication and support for self-management. Resources for adult clinical care teams and primary care providers include late-effects surveillance guidelines and web-based support services.

Selinexor is a selective inhibitor of nuclear export with anti-cancer properties. We performed a phase I study to determine the safety and maximum tolerated dose of selinexor when combined with high-dose dexamethasone, ifosfamide, carboplatin and etoposide (DICE) in relapsed/refractory T-cell lymphoma (TCL) and natural-killer/T-cell lymphoma (NKTL). Patients with relapsed/refractory TCL and NKTL were treated with standard dose ICE, dexamethasone 20 mg on days 3 to 7, and escalating doses of oral selinexor on days 3, 5 and 7 in a 3+3 design. Dose levels (DL) 1, 2 and 3 were 40, 60 and 80 mg, respectively. Eleven patients with a median age of 60 years were enrolled; six at DL1 and five at DL2. Patients had received a median of two (range, 1-4) prior lines of treatment and seven had primary refractory disease at entry into the study. Patients received a median of three cycles (range, 1-6) of selinexor-DICE. The most common grade 1 or 2 toxicities included nausea (64%), fatigue (55%), and anorexia (45%) and the most common grade 3 or 4 toxicities included thrombocytopenia (82%), anemia (82%), neutropenia (73%), and hyponatremia (73%). Two patients developed dose-limiting toxicities at DL2 and one at DL1. Five patients discontinued treatment for reasons other than disease progression or lack of response. Of the ten evaluable patients, the overall and complete response rates were 91% and 82%, respectively. The maximum tolerated dose of selinexor was 40 mg when combined with DICE. The combination showed promising complete response rates in patients with relapsed/refractory TCL and NKTL but was poorly tolerated. (clinicaltrials. gov identifier: NCT03212937).

Work-related issues among Asian adolescent and young-adult (AYA) cancer survivors are poorly described in the literature. There has also been a paucity of reports regarding insurance-related concerns in this patient population. Focus groups were therefore carried out in Singapore to understand survivorship issues related to work and insurance coverage among Asian AYA cancer survivors. Twenty-three AYA survivors and 18 healthcare professionals (HCPs) who care for AYA cancer patients were recruited for 11 focus group sessions. Thematic content analysis was carried out to identify major themes that emerged. Similar themes emerged from AYA and HCP focus groups. The majority of AYA survivors were eager to return to work post-treatment. However, some survivors were worried about not keeping up with expectations and struggled with disclosure of their medical history. In contrast, several survivors leveraged on their experience with cancer to bolster job opportunities. Despite facing challenges due to complications from cancer and restrictions at work, AYA survivors preferred to be treated normally. AYA survivors also expressed concerns about inadequate insurance coverage and a lack of information on this topic. Contrary to expectations, Asian AYA survivors are motivated to return to work and address work-related challenges. Inadequate insurance coverage remains a pressing concern despite the availability of public health insurance and subsidies. Career coaches and financial counselors should be incorporated into survivorship care to aid AYA survivors.

Contemporary data of peripheral T-cell lymphoma (PTCL) and natural-killer/T-cell lymphoma (NKTL) patients treated with ifosfamide, carboplatin and etoposide (ICE) are limited.We performed a retrospective analysis to estimate outcomes of ICE-treated PTCL and NKTL patients at three tertiary cancer centres in Singapore.Patients were identified through lymphoma databases from National Cancer Centre Singapore (NCCS), National University Hospital, Singapore (NUHS), and Singapore General Hospital (SGH). Responses and survival outcomes were determined from electronic medical records. A total of 75 patients with a median age of 50 were included. ICE was used as first-line treatment in 14 patients (19%) and as subsequent lines of treatment in 61 patients (81%). The overall response rates (ORR) for all patients was 63% (40% complete response [CR]). The ORR and CR in the first line were 86% and 64% respectively. At a median follow-up duration of 71.0 months, the median progression-free (PFS) and overall survival (OS) for all patients were 4.4 months (95%CI, 2.7-6.0) and 16 months (95%CI, 8.3-45.4) respectively.In summary, ICE showed high ORR but poor PFS in relapsed/refractory PTCL and NKTL. ORR of ICE in the first line setting appears better than real-world CHOP data and warrants further study.

Extranodal NK/T-cell lymphoma, nasal type (NKTL) is an aggressive type of non-Hodgkin lymphoma closely associated with Epstein-Barr virus and characterized by varying degrees of systemic inflammation. We aim to examine the prognostic significance of peripheral blood neutrophil-lymphocyte ratio (NLR) in patients with NKTL. Therefore, we conducted a retrospective review of 178 patients with biopsy-proven NKTL from the National Cancer Centre Singapore and Samsung Medical Center, South Korea. Using receiver operating curve analysis, an optimal cut-off for high NLR (>3.5) in predicting overall survival (OS) was derived. Survival analysis was performed using the Kaplan-Meier method and multivariable Cox proportional regression. In patients with high NLR, estimated 5-year OS was 25% compared to 53% in those with low NLR. In multivariable analysis, high NLR, in addition to age ≥60 years, presence of B-symptoms and stage III/IV at diagnosis, was independently correlated with worse OS (HR 2.08; 95% CI 1.36 to 3.18; p = 0.0008) and progression-free survival (HR 1.66; 95% CI 1.11 to 2.46; p = 0.0128). A new prognostic index (NABS score) derived from these factors stratified patients into low (0), low-intermediate (1), high-intermediate (2) and high (3–4) risk subgroups, which were associated with 5-year OS of 76.5%, 55.7%, 29.2% and 0% respectively. In conclusion, high NLR is an independent prognostic marker and the NABS model can be used to risk-stratify NKTL patients.

Background Significant progress has been made in the treatment outcomes of mantle cell lymphoma (MCL) since the introduction of cytarabine and rituximab in modern regimens. However, older patients may not readily tolerate these agents nor derive benefit. We investigated the impact of age on treatment patterns and clinical outcomes of MCL patients in an Asian population. Methods A retrospective study was conducted on patients (n = 66) diagnosed with MCL at the National Cancer Centre Singapore between 1998 and 2018. The median follow-up duration was 40 months. Survival analyses were performed using the Kaplan-Meier method and multivariate Cox proportional models. Results The median age of the cohort was 59 years (range, 26–84), with a male predominance (73%). The majority (86%) had advanced stage 3–4 disease at diagnosis. Compared with younger patients, older patients aged ≥60 years (n = 32; 48.5%) presented more frequently with B-symptoms (75% vs 38%, p = 0.0028), anaemia (75% vs 35%, p = 0.0013), and carried higher prognostic risk scores (sMIPI high risk 84% vs 56%, p = 0.016). Non-cytarabine-based induction chemotherapy was more commonly administered in older patients (76% vs 32%, p = 0.0012). The 5-year overall survival (OS) and progression-free survival (PFS) was 68 and 25% respectively. In a multivariable model, older age (HR 3.42, 95%CI 1.48–7.92, p = 0.004) and anemia (HR 2.56, 95%CI 1.10–5.96, p = 0.029) were independently associated with poorer OS while older age (HR 2.24, 95%CI 1.21–4.14, p = 0.010) and hypoalbuminemia (HR 2.20, 95%CI 1.17–4.13, p = 0.014) were independently associated with poorer PFS. In an exploratory analysis, maintenance rituximab following induction chemotherapy improved PFS in younger patients, with median PFS of 131 months and 45 months with or without maintenance therapy respectively (HR 0.39, 95%CI 0.16–0.93, p = 0.035). In contrast, no survival benefit was observed in older patients. Conclusions We demonstrated in our analysis that older patients with MCL may harbor adverse clinical features and may not derive benefit from maintenance rituximab, highlighting the need for further research in this area of need.

Ocular melanomas are uncommon cancers in Southeast Asia unlike in the West. We conducted a retrospective review of patients (n = 44) with histologically-proven ocular melanoma within a multi-ethnic Asian cohort from Singapore. Clinicopathological features and relapse patterns were examined, and survival outcomes of interest included recurrence-free survival (RFS) and overall survival (OS). Survival analysis was performed using the Kaplan–Meier method and multivariable Cox proportional regression. The study cohort included 18 male and 26 female patients, with a median age of 52 years (range 8–78). Median follow-up was 154 months. For uveal melanomas (n = 29), the 5-year RFS and OS was 56.8% and 76.6%, respectively; whilst for conjunctival melanomas (n = 15), the 5-year RFS and OS was 30.1% and 68.8%, respectively. Fifteen patients (38.5%) eventually developed metastasis, following which the median survival was only 17 months. Multivariate analysis demonstrated that higher T stage was a significant independent predictor for both OS (HR 8.69, 95% CI 1.03 to 73.09, p = 0.047) and RFS (HR 11.62, 95% CI 2.45 to 55.00, p = 0.002). Smoking history was independently predictive of better RFS (HR 0.08, 95% CI 0.01 to 0.78, p = 0.030). In conclusion, our study demonstrates the poor ocular melanoma outcomes in Southeast Asians, highlighting the necessity for urgent research in this area of unmet clinical need.

Purpose: With an increasing focus on developing survivorship services tailored for adolescent and young adult (AYA) cancer survivors, incorporation of viewpoints from both survivors and health care professionals (HCPs) is important. This study aims to explore the perceptions of current and prospective survivorship services from both groups in Singapore to propose service design and delivery strategies. Methods: Focus group discussions with 23 AYA cancer survivors between the ages of 16 and 39 years at diagnosis and 18 HCPs were conducted in National Cancer Centre Singapore (NCCS) and Singapore Cancer Society (SCS). All focus group discussions were transcribed verbatim. Deductive thematic analysis was performed according to the components of a design thinking model: empathizing with AYA survivors, defining care gaps, proposing services, and implementation strategies. Results: AYA survivors preferred age-specific services that are aligned with their personal goals. Current survivorship care failed to address the needs of survivors' dependents (caregivers and children) and to consider the utility of each service temporally. Prospective services should clarify disease disclosure obligation in job search and introduce a care navigator. Key implementation strategies included (1) training HCPs on communication techniques with AYA, (2) selecting engagement platforms that complement survivors' information-seeking behavior, (3) improving outreach to survivors through appropriate branding and publicity, and (4) consolidating services from multiple providers. Conclusions: The design of survivorship care services for AYA survivors should be systematic in its conceptualization process and employ implementation strategies. The coordination of the wide spectrum of services warrants a concerted effort by cancer centers, community partners, and the government.

Peripheral blood indices of systemic inflammation such as the neutrophil-lymphocyte ratio (NLR) have been shown to be prognostic in various cancers. We aim to investigate the clinical significance of these indices in patients with soft tissue sarcoma (STS). Seven hundred and twelve patients with available blood counts at diagnosis and/or metastatic relapse were retrospectively examined. An optimal cutoff for NLR-high (>2.5) in predicting overall survival (OS) was determined using receiver operating curve analyses. Survival analyses were performed using the Kaplan-Meier method and multivariate Cox proportional models. Our results show that NLR was significantly higher in patients with distant metastasis at diagnosis (n = 183) compared to those without (n = 529) (median: 4.36 vs 2.85, p p = 0.0003). In multivariate analysis, NLR-high was the only consistent factor independently associated with both worse OS (HR 1.53, 95% CI 1.10–2.13, p = 0.0112) and relapse-free survival (HR 1.41, 95% CI 1.08–1.85, p = 0.0125) in localized disease, as well as OS (HR 1.82, 95% CI 1.16–2.85, p = 0.0087) in metastatic/unresectable disease. In conclusion, high NLR is an independent marker of poor prognosis among patients with STS.

Author(s): Tan, Chia Jie; Mah, Jaclyn Jia Jun; Goh, Wei Lin; Poon, Eileen; Harunal Rashid, Mohamad Farid; Chan, Alexandre | Abstract: ObjectiveCancer-related cognitive impairment (CRCI) among adolescent and young adult (AYA) cancer patients with noncentral nervous system (CNS) cancers has not been well studied. In this study, we aimed to describe CRCI-associated trends and characteristics among AYA cancer patients.MethodsIn a longitudinal cohort of AYA cancer patients without CNS disease, CRCI was evaluated over 1 year using the Functional Assessment of Cancer Therapy-Cognitive Function Instrument, a self-reported cognitive outcome measure. CRCI prevalence was quantified using the previously established minimal clinically important difference. CRCI-associated longitudinal trends and factors were evaluated with mixed-effects model analysis.ResultsNinety-one patients (mean age = 28.4 ± 6.7 years) were included. Approximately one-third (34.1%) experienced CRCI at least once during the study follow-up. Female gender (P = .02), Indian ethnicity (P l .01), current smokers (P l .01), anxiety/depressive symptoms (P l .01) and fatigue (P l .01) were found to be associated with poorer cognitive function among AYAs.ConclusionsAlthough AYA cancer patients were relatively young and without CNS disease involvement, a significant proportion of them experienced clinically important decline in cognitive function. With improved understanding of this subject, effective strategies can be formulated to promote awareness of CRCI and mitigate its negative effects among AYA cancer patients.

PURPOSE: Gastrointestinal stromal tumors (GISTs) are characterized by primary mutations (PM) in KIT or PDGFRA genes. Under pharmacological pressure secondary mutations (SM) develop resulting in resistance to treatment. Our group developed a multiplex-amplicon sequencing assay that can detect PM and SM simultaneously in the plasma samples of patients with GIST, at a variant allele frequency of 0.1%. This assay was also designed to optimize detection of exon 11 mutations. PATIENTS AND METHODS: The assay was applied on 238 plasma samples obtained from 65 GIST patients. Clinical data and plasma samples were obtained from a prospective institutional database. Among the 65 patients, 34 had metastatic disease, 4 were on neoadjuvant treatment and 27 had curative surgery followed by adjuvant treatment or surveillance. There were no prespecified timepoints of plasma collection in this study. CtDNA results were correlated with clinical and radiological data. RESULTS: Overall, there was 89% concordance in detection of exon 11 mutations in tissue and plasma. 100% concordance was demonstrated for exons 9,13 and 17. The assay had a sensitivity of 75% and specificity of 94% in detecting mutations in the appropriate clinical context in the metastatic setting. Secondary mutations were detected in the appropriate clinical settings as well. In the metastatic cohort, ctDNA levels were able to correlate with disease trajectory i.e. levels decrease with response to treatment and increase with disease progression. CONCLUSION: This assay is a promising tool that can reliably and accurately detect ctDNA in GIST patients, especially the traditionally difficult exon 11 mutations. Once validated in a larger, prospective setting, this can potentially establish ctDNA as a non invasive biomarker in monitoring disease trajectory in GIST patients.

Natural-killer/T-cell lymphoma (NKTL) is a rare subset of non-Hodgkin lymphoma that demonstrates a unique geographic distribution, with higher prevalence in Asia compared to the West1. While cure remains achievable in early-stage disease, the prognosis for advanced-stage NKTL is dismal2. Recently, some progress has been made in uncovering the molecular pathogenesis of NKTL. In a genome-wide association study, strong correlations between HLA-DPB1 single-nucleotide polymorphisms and NKTL susceptibility were discovered, implicating altered antigen processing and presentation to CD4-positive T-lymphocytes in this Epstein-Barr virus (EBV)-associated malignancy3. Next generation sequencing also revealed recurrent somatic mutations such as TP53, JAK3, STAT3 and DDX3X in NKTL4,5. In this paper, we report a pair of male siblings from a non-consanguineous Chinese family who were diagnosed with NKTL, and provide initial evidence for novel recessive germline mutations in FAM160A1 identified through next-generation sequencing. The index patient was 35 years old, when he presented with nasal blockage in March 2013. 18-FDG-PET/CT imaging revealed an 18-FDG-avid nasal mass infiltrating into the palate, as well as enlarged cervical lymph nodes. Biopsy of the mass showed abnormal lymphoid cells positive for CD56 by immunohistochemistry (IHC) as well as EBV-encoded RNA (EBER) by in-situ hybridization. He was diagnosed with stage IIA extranodal NKTL, nasal type, and treated with 4 cycles of bortezomib-GIFOX (gemcitabine, ifosfamide and oxaliplatin) as part of a clinical trial followed by radiotherapy to the nasal region. He had primary-refractory disease and was further treated with 4 cycles of SMILE (dexamethasone, methotrexate, ifosfamide, l-asparaginase, and etoposide) followed by high-dose chemotherapy and autologous stem cell transplantation. He progressed and received ruxolitinib off-label, followed by RAD001 (mTOR inhibitor) and LBH589B (histone deacetylase inhibitor) as part of another clinical trial. He then had radiotherapy to an ulcerating penile lesion before he died of progressive disease 27 months after diagnosis (Supplementary Table 1). His younger brother was 18 years old, when diagnosed with NKTL affecting the nasal floor in 1998 following a bout of epistaxis. He received 6 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with high-dose methotrexate and went into complete remission. Three years later he was diagnosed with chronic myeloid leukemia, for which he received hydroxyurea. In 2004, he had a relapse of NKTL and received ESHAP (etoposide, prednisolone, cytarabine and cisplatin), total body irradiation and allogeneic bone marrow transplant. He died of transplant-related complications 6 years from diagnosis. These siblings have an older brother unaffected by any hematological malignancy. Their father died of a non-malignant condition in his fifties and their mother remains well at the age of 68 years. Among their first-degree relatives, none were known to be inflicted with hematologic malignancies (Fig. ​(Fig.11). Open in a separate window Fig. 1 Clinical characterization of brothers with familial NKTL. a 18-FDG-PET/CT image depicting a large nasal mass infiltrating into the palate, of which biopsy showed abnormal lymphoid cells positive for Epstein-Barr virus encoded RNA (EBER) by in situ hybridization. b, c Inheritance modelling identified homozygous germline mutations of FAM160A1 c.2827 C > T in both affected brothers, heterozygous carriage in their mother and paternal aunt, and homozygous wildtype in their healthy older brother. d, e The non-synonymous substitution at FAM160A1 c.2827 C > T results in an amino-acid alteration from arginine to cysteine (p.R943C). Patterns and frequencies of known mutations in other cancer types are shown

Sarcoma is an uncommon and heterogeneous group of malignancies linked by their mesenchymal origin. They are rare and account for 1% of adult cancers, and 10–20% of adolescent and young adult (AYA) cancers. While there is good published literature on the incidence and distribution of sarcoma subtypes in the western populations, there is a paucity of data from Asia, particularly on the epidemiology, treatment and outcomes of STS in Asia. Formalized prospective national registries in soft tissue sarcoma (STS) are lacking and little is known about how sarcomas are treated and managed throughout the Asia-Pacific region. Due to geographical and varying affluence levels across over 50 countries, no single uniform guideline exists across Asia to inform of chemotherapeutic options. Any existent guidelines tend to be country-specific, reflecting resource availability and geographical limitation. To understand and improve STS care in Asia, one must appreciate the macroeconomics and healthcare structures in place and to work within the limitations imposed by them. Concurrently, there exists an urgency to develop strong sarcoma centres of excellence (SCE) across Asia to deliver state-of-art care to our patients. Equally important is the need to facilitate sarcoma education to patients and healthcare workers. Development of such centres is vital in improving clinical care as they provide high-quality sub-specialized care to patients within that geographical location, serve as reference centres for knowledge and education as well as nerve centres for care-coordination in a hub-and-spoke model. Key to these centres of excellence is the sarcoma multi-disciplinary team (MDT). Studies have consistently shown that patients managed in high-volume sarcoma centres, by an expert sarcoma MDT, achieve better clinical outcomes. This report serves to highlight the challenges and opportunities of sarcoma care in Asia, map out a vision for the development of SCE across Asia and highlight the areas of potential collaboration between centres to advance the science of sarcoma.

Since few studies have investigated whether the Distress Thermometer (DT) in Asian adolescent and young adult (AYA) cancer patients (between 15 and 39 years), we investigated the appropriateness of the DT as a screening tool for psychological symptom burden in these AYA patients and to evaluate AYA patients’ distress across a trajectory of three time points longitudinally over a 6-month period. This was a prospective, longitudinal study. Recruited Asian AYA patients were diagnosed with lymphomas, sarcomas, primary brain malignancies, or germ cell tumors. Patients completed the DT, PedsQL Generic Core Scales, and the Rotterdam Symptom Checklist. Data were analyzed using STATA version 15. Approximately half of the patients experienced clinically significant DT distress (distress score ≥ 4) early in their cancer journey with 43.1% patients presenting with distress at time of diagnosis and 47.7% patients 1 month after diagnosis. Among AYA patients > 24 years old, worry (68.3%), insurance/financial issues (61%), treatment decisions (43.9%), work/school issues (41.5%), nervousness (41.5%), and sadness (41.5%) were the top five identified problems. On the other hand, the top five identified problems among AYA ≤ 24 years were worry (54.2%), nervousness (41.7%), bathing/dressing problems (37.5%), work/school issues (33.3%), and fatigue (33.3%). DT scores were significantly associated with certain psychological symptom burden items such as worry (p

Patients with clear cell renal cell carcinoma (ccRCC) have divergent survival outcomes and therapeutic responses, which may be determined by underlying molecular diversity. We aimed to develop a practical molecular assay that can identify subtypes with differential prognosis and response to targeted therapy. Whole-genome expression analysis of formalin-fixed paraffin-embedded (FFPE) material from 55 ccRCC patients was performed and two molecular subtypes with differential clinical outcomes were identified by hierarchical clustering. An eight-gene quantitative polymerase chain reaction assay for classification into two subtypes was developed for FFPE material. The primary objective was to assess assay performance by correlating ccRCC prognostic subtypes to cancer-specific survival (CSS) and, for patients receiving targeted therapy, radiologic response. In three validation cohorts, patients could be distinguished into prognostic subtypes with differential CSS (Singapore General Hospital FFPE cohort: n = 224; p = 1.48 × 10(-8); the Cancer Genome Atlas RNA-Sequencing cohort: n = 419; p = 3.06 × 10(-7); Van Andel Research Institute microarray cohort: n=174; p=0.00743). For 48 patients receiving tyrosine kinase inhibitor (TKI) treatment, the prognostic classification was associated with radiologic response to treatment (p = 5.96 × 10(-4)) and prolonged survival on TKI treatment (p=0.019). The multigene assay can classify ccRCCs into clinical prognostic subtypes, which may be predictive of response in patients receiving TKI therapy.

Introduction: Genetic predisposition to clear cell renal cell carcinoma (ccRCC) has been linked to disorders such as von Hippel-Lindau (VHL) syndrome. While twin research is a classic approach for elucidating genetic and environmental contributions to disease, no monozygotic twin-pair concordant for ccRCC in the absence of VHL syndrome has been previously reported in the literature or in major twin registries. Clinical Picture: We describe a unique monozygotic twin-pair concordant for ccRCC, with discordant but early ages of onset of 25 and 38 respectively. Cytogenetic studies and direct sequencing for VHL gene mutations in the second twin proved unremarkable. Conclusions: This is the first reported case of monozygotic twins concordant for ccRCC in the absence of VHL gene mutation. The early yet discordant, age of onset of disease in both twins suggests both genetic and environmental contributions to ccRCC. Key words: Gene-environment interaction, Kidney cancer, von Hippel Lindau syndrome

Introduction Although metastatic carcinoma in the presence of an occult primary tumor is well recognized, underlying reasons for the failure of the primary tumor to manifest are uncertain. Explanations for this phenomenon have ranged from spontaneous regression of the primary tumor to early metastasis of the primary tumor before manifestation of a less aggressive primary tumor. We report a case of 'prechronous' metastasis arising from clear cell renal cell carcinoma, where metastatic disease initially manifested in the absence of a primary renal tumor, followed by aggressive growth of the primary renal lesion. Case presentation A 43-year-old Malay man initially presented to our facility with fever and cough. He subsequently underwent surgical resection of a 9 cm right-sided lung mass found on radiological examination. Histology showed a high-grade clear cell tumor with sarcomatoid differentiation, suggestive of a metastasis from clear cell renal cell carcinoma. However, no concurrent renal lesions were noted on computed tomographic evaluation at that time. Then, four months after lung resection, he presented with a subcutaneous mass in the left loin, as well as right loin discomfort. Computed tomography scanning revealed a 10 cm right renal mass, with renal vein and inferior vena cava invasion, as well as recurrent disease in the right thorax. Histological examination of the excised subcutaneous mass revealed a high-grade carcinoma consistent with clear cell renal cell carcinoma. Conclusions This is the first reported case of prechronous metastasis of renal cell carcinoma, with metastatic disease manifesting prior to the development of the primary lesion. The underlying mechanism is uncertain, but our patient's case provides anecdotal support for the early dissemination model of metastasis.