Curative Approaches for Metaplastic Breast Cancer: A Retrospective Cohort Outcome Review.

PURPOSE: Metaplastic breast cancer (MBC) is a rare and heterogeneous breast cancer subtype, and there are critical gaps in our understanding of its long-term outcomes. This retrospective cohort study aimed to address these gaps by scrutinizing the pathologic and clinical aspects of MBC to enhance clinical decision-making and refine patient care strategies. METHODS AND MATERIALS: This registry-based retrospective cohort study included women aged ≥21 years diagnosed with MBC or matrix-producing carcinoma. The data were obtained from January 2001 to August 2020 from the Joint Breast Cancer Registry of Singapore Health Services, which included 23,935 patients. Demographic and clinicopathologic characteristics, neoadjuvant chemotherapy responses, and survival outcomes were analyzed. Statistical assessments involved univariate and multivariate Cox proportional hazards models and Kaplan-Meier survival analyses. RESULTS: This study enrolled 170 patients; 87.1% had non-metastatic disease, and 12.9% had metastatic disease. The age of patients at diagnosis ranged from 46 to 65 years (median, 56 years). The cohort's predominant characteristics were triple negative breast cancer (64%), advanced clinical stage (77.6%), node negativity (67.6%), and grade 3 disease (74.1%). In patients receiving neoadjuvant chemotherapy with curative intent treatment (17.6%), neoadjuvant chemotherapy yielded a pathologic complete response of 19.2% and a disease progression rate of 46.2%. Multivariate analysis showed that adjuvant radiation therapy significantly improved overall survival and disease-free survival, with hazard ratios of 0.29 (95% CI, 0.13-0.62; P < .005) and 0.23 (95% CI, 0.10-0.50; P < .005), respectively. Clinical T3 and T4 stages and nodal involvement were associated with poor outcomes. Stable disease after neoadjuvant chemotherapy was associated with poor overall survival and disease-free survival. CONCLUSIONS: This study sheds light on the complex landscape of MBC and emphasizes the pivotal role of adjuvant radiation therapy in enhancing patient outcomes. Despite advancements, challenges persist that warrant continued research to refine neoadjuvant chemotherapy strategies and delve into the nuanced factors that influence treatment responses.

The impact of the COVID-19 pandemic on nasopharyngeal carcinoma patients - a national cancer centre experience.

Purpose or objective: The COVID-19 pandemic has resulted in significant healthcare implications, with care for cancer patients compromised due to resource diversion towards battling the pandemic. We aim to investigate the impact of the peak wave of the pandemic in 2020 on the delivery of cancer care in Singapore, specifically via our nasopharyngeal carcinoma (NPC) treatment data. This study applies real world numbers to the impact of COVID-19 on cancer care delivery in Singapore. The choice of nasopharyngeal cancer allows a good direct estimate of common treatment measures such as time to biopsy, time to staging scans, time to treatment commencement, due to its clear protocol and algorithms for staging and treatment; thus serving as an excellent surrogate for the effectiveness and timeliness of the different aspects of cancer care delivery. Materials and methods: In this retrospective study, we included all patients with newly diagnosed NPC from 1st January to 31st May from 2017 to 2020 at our centre. This time period was chosen as it coincided with the period in 2020 during the COVID-19 pandemic where there was the most strain on healthcare resources and the most restrictions on population movement within Singapore, which may impact on healthcare seeking behaviour. Narrowing down the time period to the first 5 months of the 4 respective years also allowed us to reduce the effect of annual seasonal variation in patient numbers seen as a result of holidays and festive periods such as the Lunar New Year and scheduled school holidays. Electronic medical records (EMR) were accessed. Only newly diagnosed NPC cases were included in our analysis. Patients with second synchronous primary malignancies or NPC disease recurrence were excluded. Data analysis was carried out using a combination of SPSS and Microsoft Excel. Results: Significantly, there was a reduction of 37-46.3% in newly diagnosed NPC cases during the peak of the COVID-19 pandemic from January to end May 2020 compared to the preceding three years. Despite the reduction in numbers of newly diagnosed NPC, there was no statistically significant differences in delay from biopsy to the first radiation oncology visit and from biopsy to the first day of treatment in 2020 compared to the preceding years. All the patients treated in our centre also received the standard NPC treatment for their disease stage as per international guidelines. Conclusion: We recommend a heightened awareness of the dangers of delaying cancer presentation and care in healthcare policies and resource allocation and at the same time, encourage patient's confidence in their ability to seek care. With the resurgence of new COVID-19 variants and case numbers worldwide and in Singapore, this study focuses upon the need to be aware of the exigencies of other clinical groups in resource utilization. It would be instructive to compare this study with future long term follow up to investigate the trajectory of our cancer care delivery, as well as survival outcomes.

PSMA PET Imaging and Therapy in Adenoid Cystic Carcinoma and Other Salivary Gland Cancers: A Systematic Review.

Adenoid cystic carcinoma (ACC) and other salivary gland cancers (SGCs) are rare tumors where application of prostate specific membrane antigen (PSMA) positron emission tomography (PET) and PSMA radioligand therapy have yet to be studied extensively. This review explores the role of PSMA PET imaging and therapy as a theranostic tool for ACC and other SGCs based on current literature. A comprehensive literature search on PubMed and Embase was performed. All relevant studies containing information on PSMA PET imaging in ACC and SGC were included. Ten studies (one prospective, three retrospective, five case reports and one review paper) were included. For ACC, the mean maximum standardized uptake value (SUVmax) for local recurrence and distant metastases ranged from 2.41 to 13.8 and 2.04 to 14.9, respectively. In SGC, the meanSUVmax ranged from 1.2-12.50. Most studies observed PSMA expression positivity on immunohistochemistry (IHC) when there was PSMA PET uptake. PSMA PET was able to detect lesions not detected on standard imaging. Despite the small number of studies and wide intra-patient and inter-tumor variation of PSMA uptake in ACC and SGC, 68Gallium (68Ga)-PSMA PET has promising prospects as a diagnostic and radioligand therapeutic option. Further studies to answer the various theranostics considerations are required to guide its use in the real-world setting.

Predicting outcomes for locally advanced rectal cancer treated with neoadjuvant chemoradiation with CT-based radiomics.

A feasibility study was performed to determine if CT-based radiomics could play an augmentative role in predicting neoadjuvant rectal score (NAR), locoregional failure free survival (LRFFS), distant metastasis free survival (DMFS), disease free survival (DFS) and overall survival (OS) in locally advanced rectal cancer (LARC). The NAR score, which takes into account the pathological tumour and nodal stage as well as clinical tumour stage, is a validated surrogate endpoint used for early determination of treatment response whereby a low NAR score (< 8) has been correlated with better outcomes and high NAR score (> 16) has been correlated with poorer outcomes. CT images of 191 patients with LARC were used in this study. Primary tumour (GTV) and mesorectum (CTV) were contoured separately and radiomics features were extracted from both segments. Two NAR models (NAR > 16 and NAR < 8) models were constructed using Least Absolute Shrinkage and Selection Operator (LASSO) and the survival models were constructed using regularized Cox regressions. Area under curve (AUC) and time-dependent AUC were used to quantify the performance of the LASSO and Cox regression respectively, using ten folds cross validations. The NAR > 16 and NAR < 8 models have an average AUCs of 0.68 ± 0.13 and 0.59 ± 0.14 respectively. There are statistically significant differences between the clinical and combined model for LRFFS (from 0.68 ± 0.04 to 0.72 ± 0.04), DMFS (from 0.68 ± 0.05 to 0.70 ± 0.05) and OS (from 0.64 ± 0.06 to 0.66 ± 0.06). CTV radiomics features were also found to be more important than GTV features in the NAR prediction model. The most important clinical features are age and CEA for NAR > 16 and NAR < 8 models respectively, while the most significant clinical features are age, surgical margin and NAR score across all the four survival models.

Genomics insights into production of 2-methylisoborneol and a putative cyanobactin by Planktothricoides sp. SR001.

Planktothricoides is a free-living filamentous cyanobacterium belonging to the order Oscillatoriales and the family Phormidiaceae, capable of forming bloom in fresh and brackish waters. A unicyanobacterial non-axenic culture dominated by Planktothricoides sp. SR001 was obtained from a freshwater reservoir in Singapore. The draft genome presented here is the first tropical freshwater Planktothricoides sp. ever sequenced. The genome of 7.0Mbp contains 5,776 genes predicted using the JGI IMG pipeline. The whole genome sequence allows identification of genes encoding for nitrogen-fixation, accessory photosynthetic pigments and biosynthesis of an off-flavor compound, 2-methylisoborneol, which has been experimentally verified here based on metabolite detection. In addition, strain SR001 genome contains an operon putatively involved in the production of a linear tripeptide cyanobactin related to viridisamide A and aeruginosamide, with the later known to possess anti-microbial or cytotoxic effect.

Relationship of Microbiota and Cyanobacterial Secondary Metabolites in Planktothricoides-Dominated Bloom.

The identification of phytoplankton species and microbial biodiversity is necessary to assess water ecosystem health and the quality of water resources. We investigated the short-term (2 days) vertical and diel variations in bacterial community structure and microbially derived secondary metabolites during a cyanobacterial bloom that emerged in a highly urbanized tropical reservoir. The waterbody was largely dominated by the cyanobacteria Planktothricoides spp., together with the Synechococcus, Pseudanabaena, Prochlorothrix, and Limnothrix. Spatial differences (i.e., water depth) rather than temporal differences (i.e., day versus night) better-explained the short-term variability in water quality parameters and bacterial community composition. Difference in bacterial structure suggested a resource-driven distribution pattern for the community. We found that the freshwater bacterial community associated with cyanobacterial blooms is largely conserved at the phylum level, with Proteobacteria (ß-proteobateria), Bacteroidetes, and Actinobacteria as the main taxa despite the cyanobacterial species present and geographical (Asia, Europe, Australia, and North America) or climatic distinctions. Through multivariate statistical analyses of the bacterial community, environmental parameters, and secondary metabolite concentrations, we observed positive relationships between the occurrences of cyanobacterial groups and off-flavor compounds (2-methyisoborneol and ß-ionone), suggesting a cyanobacterial origin. This study demonstrates the potential of 16S rRNA gene amplicon sequencing as a supporting tool in algal bloom monitoring or water-resource management.

Draft Genome Sequence of a Tropical Freshwater Cyanobacterium, Limnothrix sp. Strain P13C2.

A nonaxenic unialgal culture of Limnothrix sp. strain P13C2 was obtained through multiple subculturing of an inoculum obtained from a tropical freshwater lake. Here, we report the genome of P13C2 of 4.6 Mbp, extracted from the metagenome of this coculture.

Draft Genome Sequences of Two Benthic Cyanobacteria, Oscillatoriales USR 001 and Nostoc sp. MBR 210, Isolated from Tropical Freshwater Lakes.

Genomes of two filamentous benthic cyanobacteria were obtained from cocultures obtained from two freshwater lakes. The cultures were obtained by first growing cyanobacterial trichome on solid medium, followed by subculturing in freshwater media. Subsequent shotgun sequencing, de novo assembly, and genomic binning yielded almost complete genomes of Oscillatoriales USR 001 and Nostoc sp. MBR 210.

Insights from the draft genome of the subsection V (Stigonematales) cyanobacterium Hapalosiphon sp. Strain MRB220 associated with 2-MIB production.

A non-axenic unialgal culture containing a Subsection V (Stigonematales) cyanobacterium, Hapalosiphon strain MRB 220, was obtained from a benthic freshwater algal mat through multiple transfers following growth in sterile media. Physiological characterization demonstrated the culture was capable of nitrogen-fixation and production of the off flavor compound 2-methylisoborneol (2-MIB). Total DNA isolated from this culture was sequenced using Illumina HiSeq and de novo assembled into contigs. The genome of MRB 220 was separated from co-occurring heterotrophic bacteria using sequence homology and compositional approaches, and its purity was confirmed based on best BLAST hit classification and principle component analysis of the tetranucleotide frequencies of fragmented contigs. The genome of ~7.4 Mbp contains 6,345 protein coding genes with 4,320 of these having functional prediction including predicted pathways for biosynthesis of the secondary metabolite welwitindolinone. Analyses of 16S rRNA gene and whole genome sequence average nucleotide identity indicated close relatedness of MRB 220 to the genera Hapalosiphon and Fischerella within the order Stigonematales. Microscopic examination showed that MRB 220 formed heterocystous branched filaments, thereby supporting identification of strain MRB 220 as a morphospecies of Hapalosiphon. Availability of the draft genome of Hapalosiphon strain MRB 220 enables future work to elucidate the pathway and dynamics for biosynthesis of 2-MIB and other secondary metabolites and understand the ecology and physiology of Stigonematales cyanobacteria in tropical freshwaters.

Draft Genome Sequence of Cylindrospermopsis sp. Strain CR12 Extracted from the Minimetagenome of a Nonaxenic Unialgal Culture from a Tropical Freshwater Lake.

Cylindrospermopsis is known to be one of the major bloom-forming cyanobacterial genera in many freshwater environments. We report here the draft genome sequence of a tropical Cylindrospermopsis sp. strain, CR12, which is capable of producing the hepatotoxic cylindrospermopsin.