Search

Introduction Angiosarcomas represent a rare group of soft-tissue sarcomas (1, 2) and are aggressive endothelial cell tumors of vascular or lymphatic origin. These tumors demonstrate remarkable heterogeneity in terms of [...], Angiosarcomas are rare, clinically aggressive tumors with limited treatment options and a dismal prognosis. We analyzed angiosarcomas from 68 patients, integrating information from multiomic sequencing, NanoString immuno-oncology profiling, and multiplex immunohistochemistry and immunofluorescence for tumor-infiltrating immune cells. Through whole-genome sequencing (n = 18), 50% of the cutaneous head and neck angiosarcomas exhibited higher tumor mutation burden (TMB) and UV mutational signatures; others were mutationally quiet and non-UV driven. NanoString profiling revealed 3 distinct patient clusters represented by lack (clusters 1 and 2) or enrichment (cluster 3) of immune- related signaling and immune cells. Neutrophils ([CD15.sup.+]), macrophages ([CD68.sup.+]), cytotoxic T cells ([CD8.sup.+]), Tregs ([FOXP3.sup.+]), and [PD-L1.sup.+] cells were enriched in cluster 3 relative to clusters 2 and 1. Likewise, tumor inflammation signature (TIS) scores were highest in cluster 3 (7.54 vs. 6.71 vs. 5.75, respectively; P < 0.0001). Head and neck angiosarcomas were predominant in clusters 1 and 3, providing the rationale for checkpoint immunotherapy, especially in the latter subgroup with both high TMB and TIS scores. Cluster 2 was enriched for secondary angiosarcomas and exhibited higher expression of DNMT1, BRD3/4, MYC, HRAS, and PDGFRB, in keeping with the upregulation of epigenetic and oncogenic signaling pathways amenable to targeted therapies. Molecular and immunological dissection of angiosarcomas may provide insights into opportunities for precision medicine.

Background: Peritoneal sarcomatosis (PS) is a difficult entity to treat with limited options and guarded prognosis. We aimed to determine if the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) could offer superior local recurrence-free survival in patients with retroperitoneal sarcoma at high risk of developing PS as opposed to extended resection alone. Methods: This is a single arm, phase II intervention study where all patients with recurrent localized retroperitoneal sarcoma considered at high risk of developing PS were considered for enrolment (ClinicalTrials.gov identifier: NCT03792867). Upon enrolment, patients underwent vigorous preoperative testing to ensure fitness for the procedure. During surgery, patients underwent extended resection and HIPEC with doxorubicin. Patients were followed-up every 2 weeks (± 10 days) for the first month and subsequently every three months (± 1 month) up to a year post-surgery, and were assessed for potential chemotherapy toxicity and post-treatment complications. After a year from resection and HIPEC, patients were followed-up either during routine clinic review or contacted via telephone every year (± 1 month) for 3 years. Results: Six patients were recruited but one patient dropped out due to adverse and unexpected intraoperative events. The remaining patients completed the procedure uneventfully. Post-HIPEC, all patients recurred with a disease-free interval ranging from six to 24 months. Three patients died due to complications from recurrent disease whereas the remaining three patients are alive as of their last visit. The overall survival at time at reporting ranged between 22 to 56 months. Conclusion: The procedure is feasible with no major morbidity to patients. However, we are unable to recommend for it to be implemented as a routine procedure at this current stage due to lack of improved survival outcomes. Further multi-institutional studies may be conducted to yield better results. [ABSTRACT FROM AUTHOR]

In our Asian multicenter retrospective study, we investigated the clinical prognostic factors affecting the outcomes of AITL patients and identified a novel prognostic index relevant in the Asian context. In our 174-patient cohort, the median PFS and OS was 1.8 years and 5.6 years respectively. Age > 60, bone marrow involvement, total white cell count >12 × 109/L and raised serum lactate dehydrogenase were associated with poorer PFS and OS in multivariate analyses. This allowed for a prognostic index (AITL-PI) differentiating patients into low (0-1 factors, n = 64), moderate (2 factors, n = 59) and high-risk (3-4 factors, n = 49) subgroups with 5-year OS of 84.0%, 44.0% and 28.0% respectively (p < 0.0001). POD24 proved to be strongly prognostic (5-year OS 24% vs 89%, p < 0.0001). Exploratory gene expression studies were performed and disparate immune cell profiles and cell signaling signatures were seen in the low risk group as compared to the intermediate and high risk groups. [ABSTRACT FROM AUTHOR]

Purpose: To quantify and evaluate trends of work outcomes and medical costs among Singaporean adolescent and young adult (AYA) cancer survivors. Methods: This cross-sectional study was conducted at the National Cancer Centre Singapore between July 2016 and October 2018. Cancer patients who were diagnosed between the age of 15 and 39 years and had completed treatment were eligible. Siblings of cancer patients were recruited as controls. Work outcomes were collected using an investigator-designed questionnaire, while cost data were extracted from the hospital database. Descriptive statistics were used to quantify work and cost outcomes. Mixed-effects logistic regression was used to compare employment rates between survivors and controls. Generalized linear models were used to characterize trends between medical costs and symptom burden. Results: A total of 29 cancer survivors and 23 sibling controls were analyzed. Approximately 80% of survivors and controls were employed at the time of survey; however, more than half of the employed survivors reported impaired work outcomes due to effects from cancer and cancer treatment, including work reallocation, absenteeism, and decreased work ability. Median productivity loss due to absenteeism in the past 3 months was estimated to be U.S. dollar (USD) 110. Total medical cost incurred within the first year after treatment completion remained high at a median of USD6592, with out-of-pocket expenditure between 17.2% and 100.0%. Conclusion: Despite their young age and having completed cancer treatment, Singaporean AYA cancer survivors may continue to experience poor work outcomes even after resuming work. High medical costs may also persist. [ABSTRACT FROM AUTHOR]

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 (n = 4), had dismal outcomes. Patients with adult BL, including HIV-related cases, harbor generally good prognosis in the modern era. [ABSTRACT FROM AUTHOR]

Background: There is little information about cancer‐related cognitive impairment (CRCI) in adolescent and young adults (AYA, 15–39 years old) due to its rare incidence. Here, we present the pre‐treatment (before chemotherapy or radiotherapy) evaluation of cognitive function and ability of AYA with cancer (AYAC) in a multicentered cohort study. Methods: Newly diagnosed AYAC and age‐matched healthy controls (HC) were recruited between 2018 and 2021. The primary outcome was the comparison of pre‐treatment cognitive impairment defined as 2 standard deviations (SDs) below the HC on ≥1 cognitive test, or >1.5 SDs below on ≥2 tests using CANTAB® between AYAC and HC. Secondary outcomes included self‐perceived cognitive ability assessed by FACT‐Cog v3 and biomarkers (inflammatory cytokines and brain‐derived neurotrophic factor [BDNF]). Results: We recruited 74 AYAC (median age = 34) and 118 HC (median age = 32). On objective cognitive testing, we observed three times more AYAC patients performed poorly on at least 2 cognitive tests compared to HC (40.5% vs. 13.6%, p < 0.001). AYAC self‐perceived less degree of cognitive impairment than HC (p < 0.001). However, AYAC perceived a greater impact of cognitive changes on their quality of life compared to HC (p = 0.039). Elevated baseline inflammatory markers (IL‐2, IL‐4, IL‐6, IL‐8, IL‐10 and IFN‐γ) were observed among AYAC compared to HC, and baseline BDNF was lower in AYAC compared to HC. Interaction effects between cancer diagnosis and biomarkers were observed in predicting cognitive function. Conclusion: With the pre‐existence of CRCI and risk factors of neuroinflammation even prior to systemic therapy, AYAC should receive early rehabilitation to prevent further deterioration of cognitive function after initiation of systemic therapies. (ClinicalTrials.gov Identifier: NCT03476070). [ABSTRACT FROM AUTHOR]

The six patients on rituximab who had complete or partial response to the treatment comprised three patients who had stage 4 disease and three patients who had stage 1 disease. Marginal zone B-cell lymphoma (MZL) refers to a group of lymphomas arising from B lymphocytes located in the marginal zone of secondary lymphoid follicles. In the extranodal MZL cohort, patients receiving systemic therapy had an increased risk of disease progression (HR 2.18, 95% CI 1.13-4.23, I p i = 0.020) compared against patients receiving local therapy. Compared to lung MZL and other MZL subtypes, gastric MZL and orbital MZL were more likely to present with earlier Ann Arbor stage at diagnosis ( I p i < 0.0001) (Figure 1(A)). [Extracted from the article]

Liquid biopsy circulating tumor DNA (ctDNA)-based approaches may represent a non-invasive means for molecular interrogation of gastrointestinal stromal tumors (GISTs). We deployed a customized 29-gene Archer® LiquidPlex™ targeted panel on 64 plasma samples from 46 patients. The majority were known to harbor KIT mutations (n = 41, 89.1%), while 3 were PDGFRA exon 18 D842V mutants and the rest (n = 2) were wild type for KIT and PDGFRA. In terms of disease stage, 14 (30.4%) were localized GISTs that had undergone complete surgical resection while the rest (n = 32) were metastatic. Among ten patients, including 7 on tyrosine kinase inhibitors, with evidence of disease progression at study inclusion, mutations in ctDNA were detected in 7 cases (70%). Known somatic mutations in KIT (n = 5) or PDGFRA (n = 1) in ctDNA were identified only among 6 of the 10 patients. These KIT mutants included duplication, indels, and single-nucleotide variants. The median mutant AF in ctDNA was 11.0% (range, 0.38%–45.0%). In patients with metastatic progressive KIT -mutant GIST, tumor burden was higher with detectable KIT ctDNA mutation than in those without (median, 5.97 cm vs. 2.40 cm, p = 0.0195). None of the known tumor mutations were detected in ctDNA for localized cases (n = 14) or metastatic cases without evidence of disease progression (n = 22). In patients with serial samples along progression of disease, secondary acquired mutations, including a potentially actionable PIK3CA exon 9 c.1633G>A mutation, were detected. ctDNA mutations were not detectable when patients responded to a switch in TKI therapy. In conclusion, detection of GIST-related mutations in ctDNA using a customized targeted NGS panel represents an attractive non-invasive means to obtain clinically tractable information at the time of disease progression. [ABSTRACT FROM AUTHOR]

Objective: Retroperitoneal sarcomas (RPS) comprise of 15% of soft tissue sarcomas where five-year overall survival rate is about 50%. Locoregional recurrences are observed in up to 50% of patients within the first five years following resection. Various factors have been shown to influence survival outcomes, such as histological subtype and tumour size. A nomogram for first relapse locally recurrent RPS was developed using 602 patients from 22 centres. The recurrent RPS Sarculator is available in an electronic interface and includes variables of age, size, margins of re-resection, radiotherapy, chemotherapy and histology to predict for 6-year disease-free survival (DFS) and overall survival (OS). It has not been validated externally. This study aims to validate the Sarculator recurrence nomogram in predicting the survival outcomes of recurrent RPS in an Asian population as well as examine relapse patterns. Methods: Patients diagnosed with first recurrent RPS from 1 January 2000 to 31 December 2017 with first local relapse and eligible for curative re-resection were retrospectively analysed. The type of surgery was unique for individual patients and suggestions of adjuvant therapy were based on globally recognised standards. Patients were followed up every 3 to 4 months post-operatively for the first 2 to 3 years and 6-monthly to a year thereafter. A R0 or R1 margin is deemed as complete resection, including a microscopically negative margin (R0) and microscopically positive but macroscopically clear margin (R1). R2 is classified as an incomplete resection with tumour rupture or remaining disease. Harrell's C concordance index was used to determine the nomogram's discriminative ability and calibration plots were used to assess accuracy. For the calibration, the patients were divided into 3 groups. Death data was retrieved from the National Birth and Death registry for accuracy. Results: There were 53 patients included in this study. Patient and tumour characteristics have been summarised in Table 1. All patients had their second resection at a single centre. 66.0% had their first resection at the same centre. The median age was 53 (range 21- 79) at diagnosis, median tumour size was 17cm (12cm to 28cm) and median follow-up duration was 44.1 months. The most commonly encountered subtypes were de-differentiated liposarcoma (DDLPS) (56.6%), well-differentiated liposarcoma (WDLPS) (20.8%) and leiomyosarcoma (LMS) (11.3%) with a majority being high-grade (75.5%). The median disease-free interval was 2.9 years (2- 5.3 years) from the first surgery. The median age at second surgery was 56 (21- 79) and all patients had a complete resection (R0/R1). Recurrence patterns differed with subtypes where 90.9% and 9.1% of WDLS, 76.7% and 16.7% of DDLPS and 83.3% and 16.7% of LMS had local and distant relapses respectively from the second surgery. 62.5% of distant relapses was in the lung followed by nodes (18.8%) and liver (12.5%). The 5-year OS from the second surgery was 66.2% (95% CI: 54.3%- 80.8%). The 1-year, 3 years and 6 years DFS were 50.2% (95% CI: 38.2% - 65.9%), 10.4% (4.26% - 25.5%) and 3.91% (0.684% - 22.4%) respectively. Overall, 32 patients (60.4%) had passed away from sarcoma. The concordance indices for 6-year OS and DFS were 0.7 and 0.65 (Figure 1) respectively which represents a fairly accurate prediction by Sarculator. Conclusion: Our study has shown the Sarculator nomogram for primary recurrent was applicable in our cohort and its potential application in an Asian setting. The Sarculator nomogram will be a useful tool in clinical practice to improve risk stratification and facilitate prognosis-based decision-making. Moving forward, novel therapeutic strategies are required to enhance the prognosis of patients with recurrent RPS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Angiosarcoma (AS) is a rare disease with a dismal prognosis. The treatment landscape and prognostic factors for advanced AS, including locally advanced, unresectable, and metastatic disease remain elusive. The Asian Sarcoma Consortium is an international collaborative effort to understand the sarcoma treatment landscape in Asia. We undertook a retrospective chart review of AS patients seen in 8 sarcoma academic centers across Asia. Patients with complete clinical, treatment, and follow‐up data were enrolled. Overall, 276 advanced AS patients were included into this study; 84 (30%) of the patients had metachronous metastatic AS. The median age was 67 y; primary sites of AS was cutaneous in 55% and visceral in 45% of patients. In total, 143 (52%) patients received at least 1 line of systemic chemotherapy. The most common first‐line chemotherapy regimen used was paclitaxel (47.6%) followed by liposomal doxorubicin (19.6%). The median overall survival (OS) was 7.8 mo. Significant prognostic factors for OS included age > 65 (hazard ratio (HR) 1.54, P =.006), male gender (HR 1.39, P =.02), and a cutaneous primary AS site (HR 0.63, P =.004). The median progression‐free survival (PFS) for first‐line chemotherapy was 3.4 mo. PFS for single vs combination or paclitaxel vs liposomal doxorubicin chemotherapy regimens were comparable. This study provides an insight into the treatment patterns and prognostic factors of advanced AS patients in Asia. Prognosis of advanced AS remains poor. Data from this study serve as a benchmark for future clinical study design. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Angiosarcomas of the breast (ASB) are rare, making up to less than 8% of all angiosarcomas. The surgical management for this disease continues to vary throughout centres worldwide due to the current limited evidence. We aim to examine the necessity of axillary lymph node dissection in this pathology through a retrospective study of axillary metastasis and recurrence patterns in patients treated at our institution. A retrospective review of a prospectively-maintained database was performed. All adult patients with a histologically confirmed diagnosis of ASB seen at the National Cancer Centre Singapore between 2006 and 2019 were identified. Axillary lymph node status, treatment, survival, and recurrence data were collated. Thirteen patients were identified with a confirmed diagnosis of ASB, of which there were 11 primary and 2 secondary angiosarcoma cases. Eight patients had some form of axillary lymph node dissection and 5 did not. No positive nodes were found in any examined axillary nodes despite high median number of nodes harvested (13, range 8–24). 5/13 patients had disease progression, of whom none had locoregional recurrence to the axilla. ASB continues to be rare and recurrent and presents as a challenge to treat. Axillary lymph node involvement is most likely not present in a majority of patients. Prophylactic removal is unwarranted in patients presenting without lymph node involvement due to the lack of axillary metastasis. [ABSTRACT FROM AUTHOR]

Methotrexate (MTX) is an essential chemotherapy drug used in the treatment of malignancies, but it is known to cause complications to the central nervous system. We report a case of severe MTX neurotoxicity in an adult presenting with choreoathetosis despite a normal clearance of MTX. High dose-MTX has been successfully rechallenged without any neurological sequelae. We reviewed the relevant literature of similar manifestations and summarized their clinical data, magnetic resonance imaging features and treatment given. None of them has recurrence of neurotoxicity. We concluded that it is safe to persist with MTX even after a previous episode of toxic leukoencephalopathy. [ABSTRACT FROM AUTHOR]

Background: Currently, a standardized approach to prevent and manage hepatitis B reactivation in lymphoma patients with past hepatitis exposure receiving rituximab in Singapore is lacking. This study is designed to report the current management approach and outcomes associated with hepatitis B reactivation. Objectives: The primary objective was to report 6-, 12-, 24-month cumulative hepatitis B reactivation-related outcomes. Secondary objectives were to report monitoring frequencies of hepatitis B DNA and liver function tests performed in lymphoma patients with resolved hepatitis B receiving rituximab, and anti-viral prophylaxis use. Methodology: This was a single centre, retrospective observational study. Patients with resolved hepatitis B initiated on rituximab from January 2011 to December 2015 were identified and reviewed over a two-year period starting from the date of rituximab initiation. Relevant parameters were obtained from electronic medical records. Hepatitis B reactivation was defined by hepatitis B DNA levels 20 IU/ml (1.30 log/ml) and above. Data were analysed using descriptive statistics. Results: Seventy-five patients were retrospectively reviewed over a two-year period. Hepatitis B reactivation was defined as hepatitis B DNA levels ≥20 IU/ml (1.30 log/ml). The 24-month cumulative hepatitis B reactivation rate was 4.0%. The median (interquartile range) number of hepatitis B DNA tests performed during treatment, initial six-month follow-up, and subsequent follow-up were 1.0 (0.0–2.6), 1.0 (0.0–2.0), and 1.0 (0.0–3.1), respectively. Conclusion: Large variations in hepatitis B reactivation monitoring and management strategies were observed. Further studies are required to develop and determine a standardised protocol that could contribute to safer and more cost-effective care for lymphoma patients with resolved hepatitis B on rituximab. [ABSTRACT FROM AUTHOR]