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Background: Extra-pulmonary small-cell neoplasms are rare, and treatment planning is challenging for clinicians. The lack of guideline-based management undermines and isolates patients for whom these cancers are not just rare but also real. Small-cell breast cancer (SCBC) is a rare, aggressive disease that accounts for less than 1% of all invasive breast cancers. Here, we report a case of SCBC and discuss the complexities of case management. Case Presentation: A 46-year-old patient presented with a self-detected right breast lump. Mammogram and ultrasound examination showed a 69x47mm dense lesion in the upper outer aspect of the right breast and a 17mm pathologic node in the inferior right axilla. The triple assessment demonstrated a localised high-grade malignant neuroendocrine neoplasm. Management extrapolated from small cell lung cancer management and case reports, consisted of chemotherapy with carboplatin, and etoposide introduced with concurrent radiotherapy, followed by mastectomy with axillary lymph node dissection. A complete pathological response was obtained. Six months following her surgery, metastatic disease in the brain, chest wall, lymph nodes, and lungs developed. Rechallenge with carboplatin and etoposide led to a brief response, and subsequent immunotherapy was ineffective. Conclusion: This case report highlights the challenges of rare tumour management. Establishing registries for these and other rare tumors would facilitate care, reduce patient uncertainty and assist in founding protocol-based care. [ABSTRACT FROM AUTHOR]

Background: Soft tissue sarcoma (STS) is comprised of approximately 80 subtypes, with an incidence of 4 - 5 per 100,000 annually in Europe. The National Comprehensive Cancer Network (NCCN) guidelines recommend consideration of neoadjuvant/adjuvant chemotherapy in tumors at high risk of recurrence based on the American Joint Committee on Cancer (AJCC) staging. Alternatively, the Sarculator is a risk prediction tool that has identified a threshold of risk, above which chemotherapy may provide an overall survival (OS) benefit. Using this nomogram, patients with a 10-year predicted OS < 60% are classified as high risk and should be considered for chemotherapy. The aim of this study was to assess the prognostic accuracy of these two risk prediction methods in an Irish population., Methods: All newly diagnosed patients with resected STS discussed in the STS tumor board in Cork University Hospital between January 2012 and December 2021 were identified. Clinicopathological data were collected. Risk assessment using AJCC and Sarculator nomogram was performed on all patients with an extremity/trunk sarcoma. The OS was calculated including Kaplan-Meier method for time to event analysis., Results: In total, 200 STS patients were reviewed, of whom 134 had truncal or extremity tumors. Sarculator score was calculated for 60 of these (well differentiated liposarcomas, desmoid tumors and dermatofibrosarcoma protuberans were excluded). Using the Sarculator nomogram to calculate 10-year predicted OS, 19 patients were categorized as high risk and 41 were categorized as low risk. Using AJCC staging, 25 patients were categorized as high risk and 35 as low risk. The 5-year OS rate in the Sarculator high-risk group was 60.2%, compared with 87.1% in the low-risk group (P = 0.009). The 5-year OS rate in the AJCC high-risk group was 67.6%, compared with 86.3% in the low-risk group (P = 0.083)., Conclusions: Our cohort is representative of the broad histological subtypes expected. In our population, Sarculator score results correlate with international outcomes and higher scores were associated with increased mortality. The Sarculator was more predictive of clinical outcome than AJCC staging, and its use would lower the proportion of patients being considered for adjuvant chemotherapy thereby sparing toxicity, which is important in the setting of uncertain clinical benefit., Competing Interests: The authors declare no conflict of interest., (Copyright 2024, Weadick et al.)

Introduction: The identification of genomic "targets" through next-generation sequencing (NGS) of patient's NSCLC tumors has resulted in a rapid expansion of targeted treatment options for selected patients. This retrospective study aims to identify the proportion of patients with advanced NSCLC in the Republic of Ireland whose tumors harbor actionable genomic alterations through broad NGS panel testing., Methods: Institutional review board approval was obtained before study initiation. Patients with NSCLC whose tumors underwent genomic testing through the largest available NGS panel at a nationally funded Cancer Molecular Diagnostics laboratory (St. James's Hospital) between June 2017 and June 2022 were identified. Patient demographics and tumor-related data were collected by retrospective review from all cancer centers in Ireland, referring to the Cancer Molecular Diagnostics laboratory. A total of 203 (9%) tumor samples were excluded due to insufficient neoplastic cell content. Genomic data were collected through retrospective search of Ion Reporter software. The spectrum and proportion of patients with oncogenic driver mutations were evaluated using descriptive statistics (SPSS version 29.0)., Results: In total, 2052 patients were identified. Patients were referred from 23 different hospital sites and all four geographic regions (Leinster = 1091, 53%; Munster = 763, 37.2%; Connacht = 191, 9.3%; Ulster = 7, 0.3%). Median age was 69 (range: 26-94) years; 53% were male. The most common tumor histologic subtype was adenocarcinoma (77%, n = 1577). An actionable genomic alteration was identified in 1099 cases (53%), the most common of which was KRAS (n = 657, 32%). Less frequently, NSCLC tumors harbored the following: MET exon 14 skipping (n = 53, 2.6%), MET amplification (n = 26, 1.3%), EGFR (n = 181, 8.8%), HER2 (n = 35, 1.7%), and  BRAF (n = 72, 3.5%) mutations. Fusions were detected in 76 patients (3.7%) including ALK (n = 44, 58%), RET (n = 11, 14.5%), ROS1 (n = 16, 21%), and FGFR3 (n = 5, 6.6%), whereas no NTRK fusion was identified. Co-alterations were detected in 114 patients (5.6%), the most common of which was KRAS / PIK3CA (n = 19, 17%), EGFR/PIK3CA (n = 10, 8.5%), and KRAS/IDH1 (n = 9, 8%). Other co-alterations of interest identified included KRAS G12A/ROS1 fusion (n = 1) and KRAS G12C/BRAF G469A (n = 2)., Conclusions: This is the first retrospective study to comprehensively characterize the genomic landscape of NSCLC in Ireland, using the broadest available NGS panel. Actionable alterations were identified in 53.4% of the patients, and KRAS was the most common oncogenic driver alteration. Our study revealed a lower prevalence of patients whose tumor harbors ALK , ROS1 , and RET fusions, compared with similar data sets., Competing Interests: R Keogh has received support for attending meetings from Janssen and Merck Sharp & Dohme. McMahon has received grants or contracts from 10.13039/100004319Pfizer and 10.13039/100004337Roche; consulting fees, payments, or honoraria from Pfizer; and support for attending meetings and/or travel from Pfizer and Takeda. Finn has participated on a data safety monitoring board or advisory board for Amgen, Illumina, Pfizer, and Roche; received consulting fees, payments, or honoraria from Amgen, AstraZeneca, Pfizer, and Revolution Medicines; have stocks/shares from Revolution Medicines; and received institutional support from Roche. Naidoo has received research funding from 10.13039/100004325AstraZeneca, 10.13039/100002429Amgen, 10.13039/100002491Bristol-Myers Squibb, Mirati, Roche/10.13039/100004328Genentech, Pfizer, 10.13039/100004336Novartis, Takeda, and 10.13039/100004326Bayer; consulting fees, payments, or honoraria from AstraZeneca, Amgen, Bristol-Myers Squibb, Mirati, Roche/Genentech, Pfizer, Novartis, Takeda, NGM Pharmaceuticals, Kaleido Biosciences, Elevation Oncology, and Daiichi Sankyo; and having participation on a data safety monitoring board or advisory board for Bristol-Myers Squibb, AstraZeneca, and Daiichi Sankyo. The remaining authors declare no conflict of interest., (© 2024 Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer.)