A genomic-augmented multivariate prognostic model for the survival of natural-killer/T-cell lymphoma patients from an international cohort.

With lowering costs of sequencing and genetic profiling techniques, genetic drivers can now be detected readily in tumors but current prognostic models for Natural-killer/T cell lymphoma (NKTCL) have yet to fully leverage on them for prognosticating patients. Here, we used next-generation sequencing to sequence 260 NKTCL tumors, and trained a genomic prognostic model (GPM) with the genomic mutations and survival data from this retrospective cohort of patients using LASSO Cox regression. The GPM is defined by the mutational status of 13 prognostic genes and is weakly correlated with the risk-features in International Prognostic Index (IPI), Prognostic Index for Natural-Killer cell lymphoma (PINK), and PINK-Epstein-Barr virus (PINK-E). Cox-proportional hazard multivariate regression also showed that the new GPM is independent and significant for both progression-free survival (PFS, HR: 3.73, 95% CI 2.07-6.73; p < .001) and overall survival (OS, HR: 5.23, 95% CI 2.57-10.65; p = .001) with known risk-features of these indices. When we assign an additional risk-score to samples, which are mutant for the GPM, the Harrell's C-indices of GPM-augmented IPI, PINK, and PINK-E improved significantly (p < .001, χ2 test) for both PFS and OS. Thus, we report on how genomic mutational information could steer toward better prognostication of NKTCL patients.

The treatment landscape of advanced angiosarcoma in Asia-A multi-national collaboration from the Asian Sarcoma Consortium.

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.

Phase I study of selinexor in combination with dexamethasone, ifosfamide, carboplatin, etoposide chemotherapy in patients with relapsed or refractory peripheral T-cell or natural-killer/T-cell lymphoma

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 (MTD) of selinexor when combined with high-dose dexamethasone, ifosfamide, carboplatin and etoposide (DICE) in relapsed/refractory (R/R) T-cell lymphoma (TCL) and natural-killer/T-cell lymphoma (NKTL). Patients with R/R TCL and NKTL were treated with standard dose ICE, dexamethasone 20mg on days 3 to 7, and escalating doses of oral selinexor on days 3, 5 and 7 in a 3+3 design. Dose level (DL) 1, 2 and 3 were 40, 60 and 80mg respectively. Eleven patients with a median age of 60 were enrolled; 6 at DL1 and 5 at DL2. Patients had received a median of 2 (range 1-4) prior lines of treatment and 7 had primary refractory disease at study entry. Patients received a median of 3 cycles (range 1-6) of selinexor-DICE. The most common grade (G) 1/2 toxicities included nausea (64%), fatigue (55%), and anorexia (45%) and the most common G 3/4 toxicities included thrombocytopenia (82%), anemia (82%), neutropenia (73%), and hyponatremia (73%). Two patients developed doselimiting toxicities at DL2 and one at DL1. Five patients discontinued treatment for reasons other than disease progression or lack of response. Of the 10 evaluable patients, the overall and complete response rates were 91% and 82% respectively. The MTD of selinexor was 40mg when combined with DICE. The combination showed promising CR rates in patients with R/R TCL and NKTL but was poorly tolerated.

Treatment patterns and outcomes of older patients with mantle cell lymphoma in an Asian population.

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.

Neoadjuvant tyrosine kinase inhibitors in rectal gastrointestinal stromal tumours: a provision for enhanced oncological and functional outcomes.

BACKGROUND: The role of tyrosine kinase inhibitors (TKI) in the neoadjuvant setting and the optimal duration of therapy remains poorly defined. As such, we aim to evaluate the impact of neoadjuvant TKI on oncological and functional outcomes in our cohort of patients with rectal GISTs. METHODS: A retrospective analysis of 36 consecutive patients who underwent treatment for rectal GIST at the National Cancer Centre Singapore from February 1996 to October 2017 was analysed. Surgical, recurrence and survival outcomes between the groups who underwent neoadjuvant therapy and those who underwent upfront surgery were compared. RESULTS: Patients who received neoadjuvant treatment had significantly larger tumours (median size 7.1 vs. 6.0 cm, p = 0.04) and lower mitotic count (> 10 per 50 HPF, 14 vs. 70%, p = 0.03) when compared with the non-neoadjuvant group. With TKI pre-treatment (median duration 8.8 months), majority of patients (82%) achieved at least partial response to the therapy coupled with a significant downsizing effect of up to 39% (median size of 7.1-3.6 cm), resulting in similar rates of sphincter-sparing surgery (75 vs. 76%, p = 0.94) when compared with the non-neoadjuvant group. In general, neoadjuvant group had lower rates of local recurrence (0 vs. 69%, p = 0.04) and higher overall survival (7.4 vs. 5.7 years, p = 0.03) as compared to the non-neoadjuvant group. CONCLUSIONS: Neoadjuvant TKI has the benefit of downsizing unresectable rectal GIST to benefit from sphincter-sparing procedure and also confers protection against local recurrence and improves overall survival.

Work- and insurance-related issues among Asian adolescent and young-adult cancer survivors: a qualitative study.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Management of hepatitis B reactivation in lymphoma patients on rituximab with past hepatitis B exposure: An observational study.

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.

Assessment of psychological distress among Asian adolescents and young adults (AYA) cancer patients using the distress thermometer: a prospective, longitudinal study.

PURPOSE: 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. METHODS: 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. RESULTS: 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 < 0.001), depressed mood (p = 0.020), and nervousness (p = 0.015). CONCLUSION: The DT is a useful screening tool for psychological distress in AYA cancer patients with clinically significant distress being identified in the early phases of the cancer journey.

Sarcomas Associated With Genetic Cancer Predisposition Syndromes: A Review.

UNLABELLED: : Sarcomas are rare mesenchymal malignancies that demonstrate great clinical and biological heterogeneity. A variety of sarcomas develop in the context of well-defined heritable cancer predisposition syndromes, associations that are often overlooked, given the rarity and diversity of sarcomas and the equivalent relative infrequency of cancer genetic syndromes. This review describes in detail selected heritable cancer predisposition syndromes that are known to be associated with sarcomas. Beyond the molecular and clinical features that define each syndrome, disparities in clinical presentation, natural history, and treatment of syndrome-associated compared with otherwise histologically identical sporadic sarcomas will be described. The clinical approach to selected sarcoma subsets with a view to identifying possible associations with these syndromes will then be described. Although the treatment of the majority of sarcomas will not differ significantly between sporadic cases and those associated with predisposition syndromes, knowledge of features such as unique anatomic sites of affliction or excess toxicities with particular cytotoxic therapies can facilitate alterations in therapeutic strategies to maximize efficacy and minimize toxicity. In addition, recognition of cancer genetic predisposition syndrome will allow patients and their relatives to undertake appropriate genetic counseling and testing, as well as screening, surveillance, and interventional measures, as needed. Situating sarcomas within the genetic endowment of particular patients-specifically that which confers a higher risk of malignancy-will enable clinicians to better manage the patient as a whole, complementing the great efforts currently routinely undertaken to genomically characterize somatic tumor changes with a view to achieving the dream of personalized medicine. IMPLICATIONS FOR PRACTICE: Sarcomas are uncommon malignancies that often occur sporadically but can also arise in the setting of a recognized heritable cancer predisposition syndrome. Identification of such associations when present can facilitate refinement and optimization of treatment strategies for the sarcoma so as to minimize toxicity and maximize efficacy. Discerning genetic predisposition can also facilitate institution of genetic counseling, as well as screening or surveillance schema for both the patient and his or her relatives, if required. Vigilance for these syndromes has the potential to significantly enhance the quality and comprehensiveness of sarcoma clinical management.

Malignant peripheral nerve sheath tumors.

Malignant peripheral nerve sheath tumors (MPNST) are uncommon, biologically aggressive soft tissue sarcomas of neural origin that pose tremendous challenges to effective therapy. In 50% of cases, they occur in the context of neurofibromatosis type I, characterized by loss of function mutations to the tumor suppressor neurofibromin; the remainder arise sporadically or following radiation therapy. Prognosis is generally poor, with high rates of relapse following multimodality therapy in early disease, low response rates to cytotoxic chemotherapy in advanced disease, and propensity for rapid disease progression and high mortality. The last few years have seen an explosion in data surrounding the potential molecular drivers and targets for therapy above and beyond neurofibromin loss. These data span multiple nodes at various levels of cellular control, including major signal transduction pathways, angiogenesis, apoptosis, mitosis, and epigenetics. These include classical cancer-driving genetic aberrations such as TP53 and phosphatase and tensin homolog (PTEN) loss of function, and upregulation of mitogen-activated protein kinase (MAPK) and (mechanistic) target of rapamycin (TOR) pathways, as well as less ubiquitous molecular abnormalities involving inhibitors of apoptosis proteins, aurora kinases, and the Wingless/int (Wnt) signaling pathway. We review the current understanding of MPNST biology, current best practices of management, and recent research developments in this disease, with a view to informing future advancements in patient care.

Radical resection and hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of high risk recurrent retroperitoneal sarcoma-A pilot study in a tertiary Asian centre.

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.

Outcomes of patients with resected stage III/IV acral or mucosal melanoma, treated with adjuvant anti-PD-1 based therapy.

IMPORTANCE: Acral (AM) and mucosal melanomas (MM) are rare subtypes with a poor prognosis. In those with advanced disease, anti-PD-1 (PD1) therapy has reduced activity compared to that seen in non-acral cutaneous melanoma. OBJECTIVE: To determine the efficacy of adjuvant PD1 in resected AM or MM. DESIGN: An international, retrospective cohort study SETTING: Data up to November 2021 collected from 20 centres across 10 countries. PARTICIPANTS: One hundred and ninety four patients with resected stage III or IV1 AM or MM who received adjuvant PD1 were included and compared to matched patients from the Melanoma Institute Australia (MIA) database using a propensity score matching analysis. MAIN OUTCOMES AND MEASURES: Recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and overall survival (OS) were investigated. RESULTS: Forty five of 139 (32%) AM and 9 of 55 (16%) MM patients completed adjuvant therapy. The main reason for early treatment cessation in both groups was disease recurrence: 51 (37%) and 30 (55%) in the AM and MM groups, respectively. In the AM group adjuvant PD1 was associated with a longer RFS [HR-0.69 (0.52-0.92, p = 0.0127)], DMFS [HR0.58 (0.38-0.89, p = 0.0134)] and OS [HR of 0.59 (0.38-0.92, p-value 0.0196)] when compared to the historical cohort. In the MM group there was no statistical difference in RFS [HR1.36 (0.69-2.68,p-value 0.3799], DMFS or OS. CONCLUSION AND RELEVANCE: After adjuvant PD1, both AM and MM have a high risk of recurrence. Our data suggests a benefit to using adjuvant PD1 therapy in resected AM but not in resected MM. Additional studies to investigate the efficacy of adjuvant PD1 for MM are needed.

Cutaneous versus non-cutaneous angiosarcoma: clinicopathologic features and treatment outcomes in 60 patients at a single Asian cancer centre.

BACKGROUND: Angiosarcoma (AS) is an uncommon soft tissue sarcoma with dismal prognosis that presents either cutaneously (C-AS) or non-cutaneously (NC-AS). We compared the clinical features and treatment outcomes between these 2 groups. METHODS: A single-centre study evaluating 60 AS patients between 2002 and 2012 was performed. RESULTS: The median age was 70 years. C-AS of the scalp or face comprised 66% of patients. C-AS patients were older than NC-AS (median age 74 vs. 56 years; p < 0.001). Proportionately more C-AS patients presented with non-metastatic disease (86 vs. 50%; p = 0.007). Amongst resected C-AS and NC-AS patients, rates of positive surgical margins (53 vs. 50%; p = 1.00) and adjuvant therapy (25 vs. 43%; p = 0.626) were not significantly different, though proportionately fewer C-AS patients relapsed (36 vs. 78%; p = 0.038). Paclitaxel was the most common agent in first line palliative systemic therapy, achieving an objective response rate of 56%. Median overall survival was 11.2 months, with no significant difference between C-AS and NC-AS (11.3 vs. 9.8 months; p = 0.895). CONCLUSION: Distinct from AS in the West, our series demonstrates a clear preponderance of scalp AS. Disparities in clinical characteristics between C-AS and NC-AS did not translate into survival differences.

Work Outcomes and Medical Costs Among Singaporean Adolescent and Young Adult Cancer Survivors.

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.

Imaging and treatment with 68Gallium and 177Lutetium-DOTATATE in a rare SSTR2 and ESWR1-CREM fusion positive undifferentiated round cell tumour of the lung.

The authors present a 45-year-old lady with a rare undifferentiated round cell tumour of the lung with a ESWR1-CREM fusion gene that progressed despite multiple lines of therapy. The tumour was Somatostatin Receptors Type 2 (SSTR2) positive and avid on 68Gallium-DOTATATE imaging. This allowed for novel treatment with Peptide Receptor Radionuclide Therapy (PRRT) using 177Lutetium-DOTATATE after all other standard of care options were exhausted.

Burkitt lymphoma - no impact of HIV status on outcomes with rituximab-based chemoimmunotherapy.

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.

Cognitive impairment in adolescent and young adult cancer patients: Pre-treatment findings of a longitudinal study.

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).

Clinical features and prognostic outcomes of angioimmunoblastic T cell lymphoma in an Asian multicenter study.

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.

A Systematic Review and Meta-Analysis of Mapping Biopsy for Primary Extramammary Paget's Disease in Reducing Recurrence Following Surgical Excision.

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.