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Purpose: Higher neutrophil-lymphocyte ratio (NLRs) indicate a pro-inflammatory state and are associated with poor survival. Conversely, higher albumin-globulin ratio (AGRs) may be associated with improved prognosis. We aimed to investigate the association between NLR and AGR and prognosis and survival in patients with breast cancer., Methods: This retrospective study included all patients with stage I-III breast cancer between 2011 and 2017 in Singapore General Hospital and National Cancer Center Singapore. Multivariate logistic regression analysis of NLR, AGR, age, stage, grade, and subtype was performed. Survival data between groups were compared using Cox regression analysis and log-rank tests., Results: A total of 1,188 patients were included, of whom 323 received neoadjuvant chemotherapy (NACT) and 865 underwent upfront surgery. In patients who underwent NACT, a higher AGR was significantly associated with a higher pCR rate (cut-off > 1.28; odds ratio [OR], 2.03; 95% confidence interval [CI], 1.13-3.74; p = 0.020), better DFS (cut off > 1.55; hazard ratio [HR], 0.37; 95% CI, 0.16-0.85; p = 0.019), and better CSS (cut off > 1.46; HR, 0.39; 95% CI, 0.17-0.92; p = 0.031). Higher NLR was significantly associated with worse DFS (cut off > 4.09; HR, 1.77; 95% CI, 1.07-2.91; p = 0.026) and worse CSS (cut off > 4.09; HR, 1.98; 95% CI, 1.11-3.53; p = 0.021). In patients who underwent upfront surgery, higher AGR correlated with significantly better OS (cut off > 1.17; HR, 0.54; 95% CI, 0.36-0.82; p = 0.004) and higher NLR correlated with worse OS (cut off > 2.38; HR, 1.63; 95% CI, 1.09-2.44; p = 0.018)., Conclusion: NLR and AGR are useful in predicting the response to NACT as well as prognosis of patients with breast cancer. Further studies are needed to explore their value in clinical decision making., Competing Interests: The authors declare that they have no competing interests., (© 2024 Korean Breast Cancer Society.)

Objective: To examine the association between the performance of mapping biopsies and surgical outcomes postexcision of extramammary Paget's disease (EMPD)., Background: Primary EMPD is a rare entity associated with poorly defined surgical margins and difficult-to-access sites of lesions. Surgical resection with clear margins remains the preferred management method. The use of mapping biopsies might be beneficial, particularly in lowering disease recurrence., Methods: Available literature was reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology before a fixed-effect meta-analysis was performed to identify the presence of a correlation between performing mapping biopsies and positive margins on permanent sections as well as disease-free survival. Additional study results not included in the quantitative assessment were qualitatively assessed and reported., Results: A total of 12 studies were shortlisted for final analysis. 294 patients who underwent mapping biopsies and 48 patients who did not undergo mapping biopsies were included in the assessment. Forest plot analysis revealed a pooled rate ratio of 0.50 (95% CI, 0.32-0.77) in the prevalence of positive margins in patients with mapping biopsies performed as compared to patients without. The pooled rate ratio of the prevalence of disease-free survival in patients with mapping biopsies performed as compared to patients without was 1.38 (95% CI, 1.03-1.84). Qualitative assessment of the remaining selected studies revealed equivocal results., Conclusions: Mapping biopsies are able to improve EMPD surgical excision outcomes but given the rarity of the disease and heterogeneity of mapping biopsy procedures, further confirmation with randomized controlled trials or a larger patient pool is necessary., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

(1) Background: Fluorescein sodium (Na-Fl) has been described as a safe and useful neurosurgical adjunct in adult neurooncology. However, its use has yet to be fully established in children. We designed a study to investigate the use of intraoperative Na-Fl in pediatric brain tumor surgery. (2) Methods: This is a single-institution study for pediatric brain tumor patients managed by the Neurosurgical Service, KK Women's and Children's Hospital. Inclusion criteria consists of patients undergoing surgery for suspected brain tumors from 3 to 19 years old. A predefined intravenous dose of 2 mg/kg of 10% Na-Fl is administered per patient. Following craniotomy, surgery is performed under alternating white light and YELLOW-560 nm filter illumination. (3) Results: A total of 21 patients with suspected brain tumours were included. Median age was 12.1 years old. For three patients (14.3%), there was no significant Na-Fl fluorescence detected and their final histologies reported a cavernoma and two radiation-induced high grade gliomas. The remaining patients (85.7%) had adequate intraoperative fluorescence for their lesions. No adverse side effects were encountered with the use of Na-Fl. (4) Conclusions: Preliminary findings demonstrate the safe and efficacious use of intraoperative Na-Fl for brain tumors as a neurosurgical adjunct in our pediatric patients., Competing Interests: Conflicts of InterestThe authors declare no conflict of interest., (© 2023 by the authors.)

Background: Biopsy of intrinsic brainstem tumours presumed to be diffuse midline gliomas (previously known as DIPG) is controversial. Surgery has risks of injury to the eloquent brainstem and may not have direct benefit to the patient. Technological improvements in operative adjuncts have allowed the role of biopsy for paediatric brainstem lesions to be revisited with new insights. This study aims to evaluate our institutional experience in brainstem biopsy., Methods: This is an ethics-approved retrospective study based in KK Women's and Children's Hospital. Patients diagnosed with intrinsic brainstem tumours and managed by the Neurosurgical Service were included. Variables of interest included patient demographics, neuroimaging features, type of surgery, histological and molecular diagnosis, treatment, and outcomes., Results: From 2006 to 2021, a total of 27 brainstem intrinsic tumours were referred to the Neurosurgical Service. Eleven (40.7 %) patients underwent stereotactic biopsy and 10 (37 %) had open biopsies. Histologically, 10 (37 %) were confirmed to be high grade gliomas, eight (29.6 %) were low grade gliomas and 3 (11.1 %) were malignant embryonal tumours. No negative diagnostic results or permanent postoperative complications were encountered. Five patients went on to have their tumours interrogated via next-generation sequencing to look for targetable mutations. The remaining 6 (22.2 %) patients did not undergo biopsy, whereby 1 of them is still alive after 6 years., Conclusion: Biopsy of paediatric brainstem intrinsic tumours is a safe procedure that concurrs with accurate tissue diagnosis. This option can be offered to affected patients, especially to identify relevant markers for targeted therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: Non-germinomatous germ cell tumors (NGGCTs) are rare pediatric conditions. This multicenter study using Asian multinational patient data investigated treatment outcomes and prognostic factors for NGGCTs., Methods: Medical records of 251 patients with NGGCTs treated from 1995 to 2015 were retrospectively analyzed from participating centers in Asian countries (Korea, Taiwan, Singapore, and Japan)., Results: The median follow up was 8.5 years (95% CI 7.8-9.9). In the total cohort, 5-year event-free survival (EFS) and overall survival (OS) rates were 78.2% and 85.4%, respectively. In 17.9% of the patients, diagnosis was determined by tumor markers alone (alpha-fetoprotein ≥ 10 ng/mL (Korea) or > 25 ng/mL (Taiwan and Singapore), and/or β-human chorionic gonadotropin (β-hCG) ≥ 50 mIU/mL). Patients with immature teratomas and mature teratomas comprised 12.0% and 8.4%, respectively. The 5-year EFS rate was higher in patients with histologically confirmed germinoma with elevated β-hCG (n = 28) than those in patients with malignant NGGCTs (n = 127). Among malignant NGGCTs, patients with choriocarcinoma showed the highest 5-year OS of 87.6%, while yolk sac tumors showed the lowest OS (68.8%). For malignant NGGCT subgroups, an increase in serum β-hCG levels by 100 mIU/mL was identified as a significant prognostic factor associated with the EFS and OS., Conclusion: Our result shows excellent survival outcomes of overall CNS NGGCT. However, treatment outcome varied widely across the histopathologic subgroup of NGGCT. Hence, this study suggests the necessity for accurate diagnosis by surgical biopsy and further optimization of diagnosis and treatment according to the histopathology of NGGCTs. Future clinical trials should be designed for individualized treatments for different NGGCTs subsets., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

L-type Ca V 1.3 calcium channels are expressed on the dendrites and soma of neurons, and there is a paucity of information about its role in hippocampal plasticity. Here, by genetic targeting to ablate Ca V 1.3 RNA editing, we demonstrate that unedited Ca V 1.3 ΔECS mice exhibited improved learning and enhanced long-term memory, supporting a functional role of RNA editing in behavior. Significantly, the editing paradox that functional recoding of Ca V 1.3 RNA editing sites slows Ca 2+ -dependent inactivation to increase Ca 2+ influx but reduces channel open probability to decrease Ca 2+ influx was resolved. Mechanistically, using hippocampal slice recordings, we provide evidence that unedited Ca V 1.3 channels permitted larger Ca 2+ influx into the hippocampal pyramidal neurons to bolster neuronal excitability, synaptic transmission, late long-term potentiation, and increased dendritic arborization. Of note, RNA editing of the Ca V 1.3 IQ-domain was found to be evolutionarily conserved in mammals, which lends support to the importance of the functional recoding of the Ca V 1.3 channel in brain function.

Background: This multinational study was conducted to report clinical presentations and treatment strategies in patients with intracranial germinomas across selected Asian centers, including failure patterns, risk factors, and outcomes., Methods: A retrospective data collection and analysis of these patients, treated between 1995 and 2015 from eight healthcare institutions across four countries was undertaken., Results: From the results, 418 patients were analyzed, with a median follow-up of 8.9 years; 79.9% of the patients were M0, and 87.6% had β-human chorionic gonadotropin values <50 mIU/mL. The 5/10-year overall survival (OS) and recurrence-free survival (RFS) rates were 97.2%/96.2% and 89.9%/86.9%, respectively. RFS was predicted by the radiotherapy (RT) field, with focal RT having the worst outcome, whereas chemotherapy usage had no impact on survival. Among patients who received chemotherapy, response to chemotherapy did not predict survival outcomes. In M0 patients, primary basal ganglia tumors predicted a worse RFS. In patients with bifocal tumors, an extended field RT was associated with better outcomes. In multivariable analysis, only RT fields were associated with RFS. In relapsed patients, salvage rates were high at 85.7%. Additionally, patients who received salvage RT had a better outcome (91.6% vs. 66.7%)., Conclusions: Survival outcomes of patients with germinoma were excellent. Thus, the focus of treatment for intracranial germinoma should be on survivorship. Further studies are warranted to find the optimal intensity and volume of radiation, including the role of chemotherapy in the survival of patients with intracranial germinomas, considering age, primary tumor location, and extent of disease., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The treatment of pediatric optic pathway gliomas (OPG) is challenging. At present, most centers provide individualized treatment to maximize progression free survival (PFS) and minimize morbidity. We aim to report our experience in the management of pediatric OPG, and investigate factors associated with an increased duration of remission after treatment., Methods: This is a single-institution study approved by the hospital ethics board. A retrospective review of consecutive OPGs managed from 2000 to 2020 was performed. Patients were divided into those managed with monomodality treatment (MT) and those who received combined therapy (CT). MT included various forms of surgery, chemotherapy and radiotherapy given alone, while CT involves a combination of surgery and adjuvant chemotherapy and/or radiotherapy., Results: Twenty-two patients were selected for this study. They had 40 treatment cycles; and a total follow up duration of 194.8 patient-years. Most of them were male (63.6%) and presented with visual deficits (72.7%). The mean age at initial presentation was 65 months and majority (86.4%) had their tumors arising directly from the optic chiasm, with 77.3% with hypothalamic extension. One patient had Neurofibromatosis type I (4.5%). The most common histological diagnosis was pilocytic astrocytoma (90.9%), followed by pilomyxoid astrocytoma (9.1%). The 5- and 10- year PFS were 46.2% and 36.4% respectively, while the 5- and 10-year OS were both 100%. When accounting for treatment type, there were 24 treatment cycles with MT (60.0%) and 16 CT (40.0%). After adjustment, treatments with MT were shown to have a shorter mean duration of remission (MT: 45 ± 49, CT: 84 ± 79 months; p  = 0.007). Cox regression curve plotted after adjusting for patient's age at treatment demonstrated a significantly longer PFS in the CT group ( p  = 0.037)., Conclusions: Our results suggest a significant survival benefit of CT over MT for affected patients due to the prolonged the duration of disease remission, for both primary and subsequent treatments. Nonetheless, we acknowledge that our study reflects the outcomes of treatment strategies that have evolved over time. We emphasize the need for collective efforts from a dedicated multidisciplinary team and international collaborations for better disease understanding., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lim, Tan, Ng, Seow, Chang, Wong, Looi, Low and Low.)

Purpose: Permanent tattoo marks used in radiation therapy remain for the duration of treatment and essentially for the rest of the patient's life. This study compared the initial positioning setup errors and body image perception between patients with ultraviolet (UV) and conventional dark ink tattoos., Methods and Materials: Thirty-four patients from February 2018 to March 2019, who underwent radiation therapy (RT) to the breast or chest wall for ductal carcinoma in situ or breast cancer were prospectively recruited and randomized (1:1) to receive either conventional dark ink or UV ink tattoos. Each patient received the assigned tattoos during computed tomography (CT) simulation and initial treatment setup shifts were compared. A 9-item body-image survey was administered to all patients at 3 time points: CT simulation, last week of RT, and 6 weeks post-RT. Feedback from CT and treatment staff in terms of setup time and challenges were collated., Results: The median age of the patient cohort was 46 years old. No statistically significant difference was observed between the mean setup errors for the conventional dark ink group (0.11 cm inferior, 0.01 cm left, 0.11 cm posterior) and UV ink group (0.01 cm superior, 0.01 cm right, 0.06 cm posterior; P = NS). Similar responses were observed in the body-image survey between the 2 groups across all time points (P = NS). The majority of the patients (dark ink 82.3% vs UV ink 88.2%) did not feel less sexually attractive as a result of the tattoo at 6 weeks post-RT. At 6 weeks post-RT, patients in both groups were satisfied with the appearance of the tattoo and did not feel cautious about their choice of clothes (82.4% vs 88.2%; P = NS). In addition, 88.6% of staff (n = 35) felt minimum effect of UV ink on the overall setup time, and 94.3% found no difficulty localizing the UV ink tattoos during patient positioning., Conclusions: No difference in setup accuracy was found using UV ink tattoos, and it could be implemented clinically with minimal effect on the existing workflow. Patients expressed high satisfaction and self-confidence with the use of UV ink tattoos., (Copyright © 2021 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: Whole lung irradiation (WLI) is indicated for certain pediatric patients with lung metastases. This study investigated whether WLI delivered as intensity-modulated proton therapy (IMPT) could significantly spare the heart and breasts when compared with conventional WLI delivered with anteroposterior/posteroanterior photon fields and with intensity-modulated photon therapy (IMRT) WLI., Materials and Methods: Conventional, IMRT, and IMPT plans were generated for 5 patients (aged 5-22 years). The prescription dose was 16.5 GyRBE in 1.5-GyRBE fractions. Conventional plans used 6-MV photons prescribed to the midline and a field-in-field technique to cover the planning target volume (the internal target volume [ITV] + 1 cm). IMRT plans used 6-MV photons with a 7-beam arrangement with dose prescribed to the planning target volume. IMPT plans used scenario-based optimization with 5% range uncertainty and 5-mm positional uncertainty to cover the ITV robustly. Monte Carlo dose calculation was used for all IMPT plans. Doses were compared with paired Student t test., Results: The ITV Dmean was similar for the IMPT, conventional, and IMRT plans, but the IMPT plans had a lower Dmin and a higher Dmax at tissue interfaces than conventional plans (Dmean ratio: 0.96, P  > .05; Dmin ratio: 0.9, P  < .001; Dmax ratio: 1.1, P  = .014). Dmeans for breast and heart substructures were lower with IMPT plans than with conventional/IMRT plans (heart ratios, 0.63:0.73; left ventricle ratios, 0.61:0.72; right ventricle ratios, 0.45:0.57; left atrium ratios, 0.79:0.85; right atrium ratios, 0.81:0.86; left breast ratios, 0.40:0.51; right breast ratio, 0.46:0.52; all P  < .05)., Conclusions: IMPT resulted in comparable ITV coverage and lower mean doses to the heart and breasts when compared with other techniques. Whole lung irradiation delivered as IMPT warrants prospective evaluation in pediatric patients., Competing Interests: Conflicts of Interest: Sahaja Acharya, MD, received grant funding from the Conquer Cancer Foundation of the American Society for Clinical Oncology during the conduct of this study. The authors have no other relevant conflicts of interest to disclose., (©Copyright 2021 The Author(s).)

Angiosarcomas are a rare subtype of soft-tissue sarcomas which exhibit aggressive clinical phenotypes with limited treatment options and poor outcomes. In this study, we investigated the clinical relevance of the peripheral blood neutrophil-to-lymphocyte ratio (NLR) as a marker of systemic immune response, as well as its correlation with intra-tumoral immune profiles in a subgroup of cases (n = 35) using the NanoString PanCancer IO360 panel and multiplex immunohistochemistry. In the overall cohort (n = 150), angiosarcomas of the head and neck (AS-HN) comprised most cases (58.7%) and median overall survival (OS) was 1.1 year. NLR, classified as high in 78 of 112 (70%) evaluable patients, was independently correlated with worse OS (HR 1.84, 95%CI 1.18-2.87, p = 0.0073). Peripheral blood NLR was positively correlated with intra-tumoral NLR (tNLR) (Spearman's rho 0.450, p = 0.0067). Visualization of tumor-infiltrating immune cells confirmed that tNLR scores correlated directly with both neutrophil (CD15 + cells, rho 0.398, p = 0.0198) and macrophage (CD68 + cells, rho 0.515, p = 0.0018) cell counts. Interestingly, tNLR correlated positively with oncogenic pathway scores including angiogenesis, matrix remodeling and metastasis, and cytokine and chemokine signaling, as well as myeloid compartment scores (all p < 0.001). In patients with documented response assessment to first-line chemotherapy, these pathway scores were all significantly higher in non-responders (47%) compared to responders. In conclusion, systemic and local immune responses may inform chemotherapy response and clinical outcomes in angiosarcomas.

Introduction: End-of-life patients face difficulties in reporting respiratory distress. The Respiratory Distress Observation Scale (RDOS) is a well-known tool; however, field implementation has been challenging from ground feedback. We sought to develop a simpler scale. Setting: Patients referred for palliative consult in a tertiary hospital in Singapore were recruited. Methods: A priori , we identified 18 dyspnea physical signs and documented their presence through bedside observation. Dyspnea severity was self-reported. The cohort was randomly split into training and test sets. Partial least square regression with leave-one-out cross-validation was used to develop a four-point model from the training set. Using the test set, data fit was compared using Akaike and Bayesian Information Criterion. Discrimination was assessed using receiver operating characteristics. Results: Of 122 patients, mean age was 67.9 years (range 23-93, standard deviation 12.9), 71.3% had a primary cancer diagnosis, and 58.1% were chair/bedbound with a Palliative Performance Scale of ≤50. Median reported dyspnea scale was 5 (interquartile range 3-7). Our model (modRDOS-4) consisted of four predictors (grunting, respiratory rate, accessory muscle use, paradoxical breathing). A modRDOS-4 of ≥6 identified moderate-to-severe dyspnea with a sensitivity of 0.78 and specificity of 0.90. Using the test set, with the modRDOS-4, the Akaike Information Criterion (AIC) is 149.8, Bayesian Information Criteria (BIC) is 154.1, and the receiver operating characteristics (ROC) is 0.74. With the original RDOS, the AIC is 145.2, BIC is 149.5, and ROC is 0.76. Conclusion: For a quick assessment of dyspnea, we developed a four-item tool with a pilot web-based nomogram. External validation is needed., Competing Interests: No competing financial interests exist., (© Ru Xin Wong et al., 2020; Published by Mary Ann Liebert, Inc.)

Background: Socioeconomic status (SES) is likely to affect survival in breast cancer patients. Housing value is a reasonable surrogate for SES in Singapore where most residents own their own homes, which could be public (subsidised) or private housing. We evaluated effects of housing value and enhanced medical subsidies on patients' presentation, treatment choices, compliance and survival in a setting of good access to healthcare., Methods: A retrospective analysis of breast cancer patients treated in a tertiary hospital cluster from 2000 to 2016 was performed. Individual-level Housing value Index (HI) was derived from each patient's address and then grouped into 3 tiers: HI(high)(minimal subsidy), HI(med)(medium subsidy) and HI(low)(high subsidy). Cox regression was performed to evaluate the associations between overall survival (OS) and cancer-specific survival (CSS) with HI and various factors., Findings: We studied a multiracial cohort of 15,532 Stage 0-IV breast cancer patients. Median age was 53.7 years and median follow-up was 7.7 years. Patients with lower HI presented with more advanced disease and had lower treatment compliance. On multivariable analysis, compared to HI(high) patients, HI(med) patients had decreased OS (HR=1.14, 95% CI 1.05-1.23) and CSS (HR=1.15, 95% CI 1.03-1.27), and HI(low) patients demonstrated reduced OS (HR=1.16, 95% CI 1.01-1.33). Ten-year non-cancer mortality was higher in lower HI-strata. Enhanced medical subsidy approximately halved treatment noncompliance rates but its receipt was not an independent prognostic factor for survival., Interpretation: Despite good healthcare access, lower-HI patients have poorer survival from both cancer and non-cancer causes, possibly due to delayed health-seeking and poorer treatment compliance. Enhanced subsidies may mitigate socioeconomic disadvantages., Funding: None., Competing Interests: We declare no competing interests., (© 2020 The Author(s). Published by Elsevier Ltd.)

Purpose: Breast phyllodes tumors (PT) are classified into benign, borderline, and malignant grades based on histopathologic characteristics. Specific to malignant PT (MPT), surgery is the mainstay yet relapse rates are high and knowledge gaps in the literature exist regarding adjuvant radiotherapy (RT). We aimed to investigate the outcomes of patients with MPT treated in a tertiary Asian institution., Methods and Materials: Patients with nonmetastatic MPT treated from February 1992 to June 2019 were analyzed retrospectively. RT details and relapse fields were studied. Outcomes of patients with and without RT were compared and hazard ratios were calculated using Cox proportional hazard test. Multivariable analysis was performed., Results: Twenty-two of 89 patients received adjuvant RT and the median dose was 60 Gy. In the no-RT group, 4 patients received RT on relapse and had no further recurrences; a further 2 received RT for fungating relapses with good symptomatic relief. RT was only increasingly prescribed after 2004. Median follow-up in the RT group was 3.31 years, compared with 6.17 years in the no-RT group. In the RT group, 15 patients (68.2%) underwent mastectomy, versus 39 (58.2%) in the no-RT group. One patient in the RT group developed an infield local relapse, compared with 21 of 67 patients in the no-RT group. Multivariate model showed that RT decreased risk of locoregional failure (hazard ratio 0.12, 95% confidence interval [CI] 0.02-0.92, P = .04). Three-year locoregional recurrence-free survival was higher in the RT group, 92.3% (95% CI, 78.9-100) versus 73.3% (95% CI, 63.1-85.1) in the no-RT group (P = .03). There were no differences in 3-year survival., Conclusions: We recommend that adjuvant radiotherapy be discussed for malignant PT for local control, even after mastectomy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aim: To study the applicability of 2 common nomograms in retroperitoneal sarcoma patients treated in an Asian tertiary hospital, and to study relapse patterns., Methods: Patients from 1st January 2000 to 31st December 2017 were retrospectively analysed. R2 resection from an external institution were ineligible. Harrel's C concordance index and calibration plots were used to assess nomograms' accuracy., Results: 109 patients were eligible, with a median age of 56, median tumour size of 16 cm and median follow up of 44.1 months. Most common subtypes were DDLPS (46.8%), LMS (19.3%) and WDLPS (13.8%). Overall, 81.1% had passed away from sarcoma. Recurrence patterns differed with subtypes; 6.7% of WDLPS and 66.7% of LMS had distant relapses. WDLPS patients had a median sarcoma specific survival of 139 months (122-NA), while the rest had a median SSS of 72.3 months (59.7-NA). The 5-years and 7-year OS were 63.0% (95% CI: 53.6%-74.0%) and 51.6% (41.1%-64.8%) respectively. The 5-years and 7-year DFS were 22.4% (15.5%-32.3%) and 17.5% (11%-27.8%) respectively. The 4-years, 8-years and 12-year SSS were 71.3% (62.7%-81.0%), 51.8% (40.8%-65.8%) and 32.2% (19.7%-52.6%) respectively. The concordance indices for 7-year DFS and OS (Sarculator) were 0.63 and 0.73. The concordance indices for 4-, 8- and 12-year SSS (MSKCC) were 0.64, 0.72 and 0.72., Conclusion: Both nomograms were effective in our cohort. Both nomograms can be further improved by specifying the type of relapse and including a longer-term endpoint for the Sarculator., Competing Interests: Declaration of competing interest None., (Copyright © 2020. Published by Elsevier Taiwan LLC.)

The ensuing COVID-19 pandemic poses unprecedented and daunting challenges to the routine delivery of oncological and supportive care to patients with breast cancer. Considerations include the infective risk of patients who are inherently immunosuppressed from their malignancy and therapies, long-term oncological outcomes from the treatment decisions undertaken during this extraordinary period, and diverted healthcare resources to support a coordinated whole-of-society outbreak response. In this review, we chronicle the repercussions of the COVID-19 outbreak on breast cancer management in Singapore and describe our approach to triaging and prioritising care of breast tumours. We further propose adaptations to established clinical processes and practices across the different specialties involved in breast oncology, with references to the relevant evidence base or expert consensus guidelines. These recommendations have been developed within the unique context of Singapore's public healthcare sector. They can serve as a resource to guide breast cancer management for future contingencies in this city-state, while certain elements therein may be extrapolatable to other medical systems during this global public health emergency.

Background: Metastatic medulloblastoma (MB) portends a poor prognosis. Amongst the 4 molecular subtypes, Group 3 and Group 4 patients have a higher incidence of metastatic disease, especially involving the neuroaxis. At present, mechanisms underlying MB metastasis remain elusive. Separately, inflammation has been implicated as a key player in tumour development and metastasis. Cytokines and their inflammation-related partners have been demonstrated to act on autocrine and, or paracrine pathways within the tumour microenvironment for various cancers. In this study, the authors explore the involvement of cerebrospinal fluid (CSF) cytokines in Group 3 and 4 MB patients with disseminated disease., Methods: This is an ethics approved, retrospective study of prospectively collected data based at a single institution. Patient clinicpathological data and corresponding bio-materials are collected after informed consent. All CSF samples are interrogated using a proteomic array. Resultant expression data of selected cytokines are correlated with each individual's clinical information. Statistical analysis is employed to determine the significance of the expression of CSF cytokines in Group 3 and 4 patients with metastatic MB versus non-metastatic MB., Results: A total of 10 patients are recruited for this study. Median age of the cohort is 6.6 years old. Based on Nanostring gene expression analysis, 5 patients have Group 3 as their molecular subtype and the remaining 5 are Group 4. There are 2 non-metastatic versus 3 metastatic patients within each molecular subtype. Proteomic CSF analysis of all patients for both subtypes show higher expression of CCL2 in the metastatic group versus the non-metastatic group. Within the Group 3 subtype, the MYC-amplified Group 3 MB patients with existing and delayed metastases express higher levels of CXCL1, IL6 and IL8 in their CSF specimens at initial presentation. Furthermore, a longitudinal study of metastatic Group 3 MB observes that selected cytokines are differentially expressed in MYC-amplified metastatic Group 3 MB, in comparison to the non-MYC amplified metastatic Group 3 MB patient., Conclusion: This study demonstrates higher expression of selected CSF cytokines, in particular CCL2, in metastatic Group 3 and 4 MB patients. Although our results are preliminary, they establish a proof-of-concept basis for continued work in a larger cohort of patients affected by this devastating disease.

Background: Breast cancer (BC) patients with brain metastases (BM) are heterogeneous with markedly variable survival. The Breast Graded Prognostic Assessment (B-GPA) and Modified B-GPA (mB-GPA) have been proposed as useful tools for stratifying survival in this population. However, extra-cranial disease progression, a clinically important variable, is not incorporated into the final model. We undertook the validation of B-GPA and mB-GPA in an Asian cohort and further explore extra-cranial disease progression as a prognostic factor., Methods: Data of BC patients with newly diagnosed BM between 2006 and 2017 was extracted retrospectively from a prospectively maintained institutional database. Patients were classified based on their B-GPA and mB-GPA scores. Univariate (UVA) and multivariate analysis (MVA) using the Cox proportional hazard model were performed to investigate the factors prognostic of overall survival (OS). The Kaplan-Meier method was used to estimate OS and log-rank test to compare survival between scores. The performances of B-GPA and mB-GPA were compared using Harrell's concordance index (C-index) and Akaike information criterion (AIC)., Results: In our cohort of 282 patients, the B-GPA and mB-GPA were validated as prognostic tools for OS, demonstrating excellent separation between survival curves (P <0.001). In MVA, we found all components of mB-GPA (age, performance status, number of BM, tumour subtype) to be independent predictors of survival. C-index was 0.64 and AIC was 2,483.39 for B-GPA. mB-GPA demonstrated marginally better discrimination with a C-index of 0.65 and AIC of 2,445.78. Extra-cranial progression was an independent predictor for survival in our population (P <0.001)., Conclusions: The mB-GPA incorporates four simple clinical variables each of independent prognostic significance. Both B-GPA and mB-GPA demonstrate moderate discriminative capabilities for OS with mB-GPA performing marginally better. Inclusion of extra-cranial disease progression as a factor in future model development may further improve its prognostic value.

Purpose: The American Joint Committee on Cancer 8th edition (AJCC8) prognostic stage (PS) was implemented January 1, 2018, but it is complex due to multiple permutations. A North American group proposed a simpler system using the anatomic stage with a risk score system (RSS) of 1 point each for grade 3 tumor and human epithelial growth factor receptor 2 (HER2) and estrogen receptor (ER) negativity. Here we aimed to evaluate this risk score system with our database of Asian breast cancer patients and compare it against the AJCC8 PS., Methods: Patients diagnosed with breast cancer stage I-IV in 2006-2012 were identified in the SingHealth Joint Breast Cancer Registry. Five-year breast cancer-specific survival (CSS) and overall survival (OS) were calculated for each anatomic stage according to the risk score and compared with the AJCC8 PS., Results: A total of 6,656 patients were analyzed. The median follow-up was 61 (interquartile range, 37-90) months. There was a high receipt of endocrine therapy (84.6% of ER+ patients), chemotherapy (84.3% of node-positive patients), and trastuzumab (86.0% of HER2+ patients). Within each anatomic stage, there were significant differences in survival in all sub-stages except IIIB. On multivariate analysis, the hazard ratio for negative ER was 1.74 (1.48-2.06), for negative HER2 was 1.49 (1.26-1.74), and for grade 3 was 1.84 (1.55-2.19). On multivariate analysis controlled for age, ethnicity, and receipt of chemotherapy, the RSS (Akaike information criterion [AIC] = 10,649.45; Harrell's Concordance Index [C] = 0.85) was not inferior to the AJCC8 PS (AIC = 10,726.65; C = 0.84) for CSS, nor was the RSS (AIC = 14,714.4; C = 0.82) inferior to the AJCC8 PS (AIC = 14,784.69; C = 0.81) for OS., Conclusion: The RSS is comparable to the AJCC8 PS for a patient population receiving chemotherapy as well as endocrine- and HER2-targeted therapy and further stratifies stage IV patients., Competing Interests: Conflict of Interest: The authors declare that they have no competing interests.

Aims: We aim to validate the AJCC 8th edition prognostic staging system for breast cancer in an Asian setting., Methods: Clinico-pathologic information and cancer-specific survival (CSS) outcomes of 6287 stage I to III patients with invasive breast cancer who underwent upfront surgery at SingHealth institutions in Singapore from 2006 to 2014 were analyzed. Survival distributions for the different staging systems were estimated by the Kaplan-Meier method and compared using the log-rank tests. Multivariable Cox proportional hazards models were used, with Akaike Information Criterion (AIC) and Harrell's Concordance Index (C-index) to compare both staging systems. Among patients with positive hormone-receptor status, 84.8% received endocrine therapy. Among the cohort, 60.3% of received chemotherapy; 82.1% of node positive patients received chemotherapy and 86.0% of HER2-enriched patients in whom chemotherapy was also indicated received adjuvant HER2-targeted therapy. Ninety-seven percent of patients received anthracyclines and/or taxanes containing chemotherapy regime., Results: The median follow up was 64 months. 2921 patients (46.5%) were discordant between the anatomic and prognostic systems of which 363 (5.8%) were upstaged and 2558 (40.7%) were down-staged. For all patients, stages in both the prognostic and anatomic systems were discriminating for 5-year CSS. Controlling for age, ethnicity and receipt of chemotherapy, the prognostic staging system model (AIC = 7538.87, C = 0.79) presented slightly better explanation and concordance of survival times than the anatomic staging system model (AIC = 7607.31, C = 0.77)., Conclusion: The prognostic staging system was better than the anatomic staging system in predicting outcomes but the anatomic system remains relevant due to its ease of use., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Lichen myxedematosus is an idiopathic, cutaneous mucinosis with 2 clinicopathologic subsets. There is the generalised papular and sclerodermoid form, more properly termed scleromyxedema, and the localised papular form. We report the first case, to our knowledge, of lichen myxedematosus in association with rheumatoid arthritis as well as a case in association with dermatomyositis. An up-to-date literature review on cutaneous mucinoses and connective tissue diseases, excluding the common association of primary and secondary mucinoses with systemic lupus erythematosus, was also performed.

Introduction: This study aimed to describe the knowledge, attitudes and practices of young women regarding human papillomavirus (HPV) vaccination., Methods: We conducted a descriptive, cross-sectional, questionnaire-based study among female students at a tertiary institute in Singapore., Results: A total of 255 questionnaires were completed and formed the basis of the analysis. 244 (95.7%) of the total participants were of the age group 15-22 years. 252 (98.8%) participants were unmarried and 240 (94.1%) had never had sexual intercourse. Only 25 (9.8%) women had received vaccination. Among the unvaccinated participants, 96 (41.7%) had no intention to receive HPV vaccination and 62 of them cited lack of information as a major barrier to HPV vaccination. Knowledge of cervical cancer and HPV vaccination was also assessed and graded via a point system, with a maximum score of 14. Knowledge was found to be low, with a median score of 7. There was a significant association between HPV vaccination uptake and the source from which they first heard about the vaccine (p = 0.007). Vaccinated respondents tended to first hear about it from their relatives and friends, as compared to unvaccinated respondents (60.0% vs. 27.0%)., Conclusion: There is poor uptake of HPV vaccination amongst Singapore's susceptible youth as well as poor knowledge of cervical cancer and HPV vaccination. Public health education regarding cervical cancer and HPV vaccination is still needed and has to be targeted at not only respondents, but also their family and friends., (Copyright: © Singapore Medical Association.)

Background and Purpose: A planning margin ⩽3 mm is employed in some head-and-neck IMRT cases due to the proximity of critical structures. This study aims to explore the need to redefine the action-level in the head-and-neck imaging protocol in consideration of the intra-fraction movement., Material and Methods: This is a local study of 18 patients treated using the same immobilisation system and setup protocol. Post-treatment orthogonal pair of kilovoltage X-ray images was acquired on the first three days of treatment. 106 sets of pre- and post-treatment kV X-ray images acquired over 53 fractions were analysed against the treatment planning DRR for calculation of intra-fraction movement., Results: Individual mean intra-fraction movement in all directions ranged from -1.8 to 1.1 mm. Population mean (median) intra-fraction movement in the x-, y-, and z-planes were -0.1 mm (0 mm), -0.3 mm (-0.3 mm) and -0.2 mm (-0.2 mm) respectively. Intra-fraction movement in all three dimensions, x-, y- and z-planes were considered statistically significant (p<0.05). 7 out of 53 fractions (13.2%) were highlighted as the combined magnitude of the intra-fraction motion with the uncorrected pre-treatment setup errors had exceeded the boundaries of given margins., Conclusions: 3 mm-AL was not adequate to account for intra-fraction movement when the CTV-PTV margin was ⩽3 mm and should be excluded from the routine imaging protocol and daily image-guided radiotherapy should be employed. Adjusting the action-level to 2 mm would allow a more confident approach in delivery of the prescribed dose in head-and-neck IMRT cases., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Eosinophilia is commonly encountered during clinical practice. Some can be attributed to well-defined causes while others cannot. Optimal management of hypereosinophilia with unknown aetiology is uncertain as the natural history is not well described., Methods: We retrospectively studied patients with hypereosinophilia (>5 × 10(9)/L) and described the characteristics, natural history and treatment of those with eosinophilia of uncertain aetiology., Results: There were 141 patients with hypereosinophilia: 87 with well-defined causes, 54 with uncertain aetiology. The latter was managed as hypereosinophilic syndrome (HES) (n = 5), idiopathic hypereosinophilia (IH) (n = 11), presumptive helminthic infection (n = 11) and reactive eosinophilia (n = 5), while 22 were insufficiently investigated and did not have definite working diagnoses. Their median age and peak eosinophil count were 64 (22 to 94) years and 10.0 (5.2-33.9) × 10(9)/L respectively. Forty-six per cent had symptoms attributable to eosinophilia, with the HES and insufficiently investigated groups having the highest (100%) and lowest (27%) percentages respectively. HES and IH patients were most extensively investigated. All 14 HES or IH patients who received steroids responded. All presumptive helminthic infection patients received mebendazole: nine responded, and two had unassessable responses. For the remaining patients, seven received steroids and all responded; one received mebendazole but defaulted; 19 were not treated: 11 resolved spontaneously. No non-HES patients developed eosinophilia-related organ dysfunction. No mortality was caused by hypereosinophilia., Conclusions: Patients with hypereosinophilia of uncertain aetiology can be empirically managed according to working diagnoses derived from history taking, examination and selective investigations. Most patients have benign short-term outcomes, but longer monitoring is required to assess long-term outcomes from untreated hypereosinophilia., (© 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.)

The present study investigated the tenderisation effects ultrasound processing (UT) on farmed cobia sashimi. Age-treated cobia trunk muscles (AT) were used as the control. The pH, total volatile base nitrogen, trimethylamine nitrogen, thiobarbituric acid reactive substances, ATP catabolism components, K 1 value, and texture were evaluated. The texture of AT sashimi reached the optimal firmness range with 8.53N at day 7. However, AT samples could not be served raw after day 7 because of their poor freshness indexes, including a TVBN value of 18.53g/100g, a TMAN value of 3.25mg/100g, and a TBARS value 0.983MDAmg/100g. Moreover, the K 1 value of AT sashimi was 20.21% at day 5. UT was employed to efficiently tenderise cobia sashimi with an initial firmness of 9.70-7.82N after 90min of treatment. The results of this study indicate that UT accelerates the biochemical reaction rate, as evidenced by the increases in the TVBN, TMAN, and TBARS contents; however, these values were very low. The results of this study could provide basic information for the development of a novel ultrasonic tenderisation technique in raw seafood designed for restaurants and consumers., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Death receptor-dependent apoptosis is an important mechanism of growth control. It has been demonstrated that Ras association domain family protein 1A (RASSF1A) is a tumor suppressor protein involved in death receptor-dependent apoptosis. However, it is unclear how RASSF1A-mediated cell death is initiated. We have now detailed 14-3-3 dependent regulation of RASSF1A-mediated cell death. We demonstrate that basal association of RASSF1A with 14-3-3 was lost following stimulation with tumor necrosis factor alpha (TNFalpha) or TNFalpha related apoptosis inducing ligand (TRAIL). Subsequent to the loss of 14-3-3 association, RASSF1A associated with modulator of apoptosis (MOAP-1) followed by death receptor association with either TNFalpha receptor 1 (TNF-R1) or TRAIL receptor 1 (TRAIL-R1). 14-3-3 association required basal phosphorylation by the serine/threonine kinase, glycogen synthase kinase 3beta (GSK-3beta), on serine 175, 178, and 179. Mutation of these critical serines resulted in the loss of 14-3-3 association and earlier recruitment of RASSF1A to MOAP-1, TNF-R1, and TRAIL-R1. Furthermore, stable cells containing a triple serine mutant of RASSF1A [serine (S) 175 to alanine (A) [S175A], S178A, and S179A] resulted in increased basal cell death, enhanced Annexin V staining and enhanced cleavage of poly (ADP-ribose) polymerase (PARP) following TNFalpha stimulation when compared to stable cells containing wild type RASSF1A. RASSF1A-mediated cell death is, therefore, tightly controlled by 14-3-3 association.