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Hikmat Abdel-Razeq,1,2 Fawzi Abu Rous,3 Fawzi Abuhijla,4 Nayef Abdel-Razeq,3 Sarah Edaily1 1Department of Internal Medicine, King Hussein Cancer Center, Amman, Jordan; 2School of Medicine, The University of Jordan, Amman, Jordan; 3Henry Ford Health System, Detroit, MI, USA; 4Department of Radiation Oncology, King Hussein Cancer Center, Amman, JordanCorrespondence: Hikmat Abdel-Razeq, Department of Internal Medicine, King Hussein Cancer Center, 202 Queen Rania Al Abdullah Street, Amman, 11941, Jordan, Tel +962-6 5300460, Ext: 1000, Email habdelrazeq@khcc.joAbstract: Breast cancer is the most common cancer diagnosed among women worldwide and more than half are diagnosed above the age of 60 years. Life expectancy is increasing and the number of breast cancer cases diagnosed among older women are expected to increase. Undertreatment, mostly due to unjustifiable fears of advanced-age and associated comorbidities, is commonly practiced in this group of patients who are under-represented in clinical trials and their management is not properly addressed in clinical practice guidelines. With modern surgery and anesthesia, breast surgeries are considered safe and is usually associated with very low complication rates, regardless of extent of surgery. However, oncoplastic surgery and management of the axilla can be tailored based on patients’- and disease-related factors. Most of chemotherapeutic agents, along with targeted therapy and anti-Human epidermal growth factor receptor-2 (HER2) drugs can be safely given for older patients, however, dose adjustment and close monitoring of potential adverse events might be needed. The recently introduced cyclin-D kinase (CDK) 4/6-inhibitors in combination with aromatase inhibitors (AI) or fulvestrant, which changed the landscape of breast cancer therapy, are both safe and effective in older patients and had substituted more aggressive and potentially toxic interventions. Despite its proven efficacy, adjusting or even omitting adjuvant radiation therapy, at least in low-risk older patients, is safe and frequently practiced. In this paper, we review existing data related to breast cancer management among older patients across the continuum; from resection of the primary tumor through adjuvant chemotherapy, radiation and endocrine therapy up to the management of recurrent and advanced-stage disease.Keywords: breast cancer, age, elderly patients, geriatric

Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis, as described in the ASCO Guidelines Methodology Manual . ASCO Living Guidelines follow the ASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines . Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating clinician and do not account for individual variation among patients. See the Appendix for disclaimers and other important information (Appendix 1 and Appendix 2 , online only). Updates are published regularly and can be found at https://ascopubs.org/nsclc-da-living-guideline .

Introduction: Amplification of 3q is the most common genetic alteration identified in squamous cell carcinoma of the lung (LUSC), with the most frequent amplified region being 3q26 to 3q28., Methods: In this analysis, we aim to describe the prognostic relevance of 3q amplification by focusing on a minimal common region (MCR) of amplification constituted of 25 genes. We analyzed 511 cases of LUSC from The Cancer Genome Atlas and included 476 in the final analysis., Results: We identified a 25-gene MCR that was amplified in 221 (44.3%) cases and was associated with better disease-specific survival (not reported [NR] versus 9.25 y, 95% confidence interval [CI]: 5.24-NR, log-rank p  = 0.011) and a progression-free interval of 8 years (95% CI: 5.1-NR) versus 4.9 years (95% CI: 3.5-NR, log-rank p  = 0.020). Multivariable analysis revealed that MCR amplification was associated with improved disease-specific survival and progression-free interval., Conclusions: Amplification of the 25-gene MCR within 3q was present in 44% of this cohort, consisting mainly of Caucasian patients with early stage LUSC. This analysis strongly indicates the prognostic relevance of the 25-gene MCR within 3q. We are further evaluating its prognostic and predictive relevance in a racially diverse patient population with advanced LUSC., (© 2023 The Authors.)

In March 2020, WHO declared COVID-19 a global pandemic which led to many countries closing their borders to contain the spread of the virus, stay-at-home mandates were announced and governmental entities started working on minimal capacity. Delays in visa processing and renewal is one aspect that was hugely impacted by the pandemic and led to interruption in the training of many international medical graduates (IMGs). In this manuscript, we share our stories and perspective on the challenges faced by IMGs holding J-1 visa during COVID-19 pandemic.

The therapeutic landscape of lung cancer treatment is changing rapidly, and new data was presented at the recently concluded American Society of Clinical Oncology 2022 (ASCO22) meeting. We highlight studies of clinical relevance that represent significant updates in the current management of non-small cell lung cancer (SCLC) and small cell lung cancer (NSCLC). We summarize the updates in early-stage NSCLC, mutated and non-mutated advanced NSCLC as well as small cell lung cancer (SCLC), and discuss these advances in the context of the current clinical standard of care.

Over the last decade, the use of targeted therapies and immune therapies led to drastic changes in the management lung cancer and translated to improved survival outcomes. This growing arsenal of therapies available for the management of non-small cell lung cancer added more complexity to treatment decisions. The genomic profiling of tumors and the molecular characterization of the tumor microenvironment gradually became essential steps in exploring and identifying markers that can enhance patient selection to facilitate treatment personalization and narrow down therapy options. The advent of innovative diagnostic platforms, such as next-generation sequencing and plasma genotyping (also known as liquid biopsies), has aided in this quest. Currently, programmed cell death ligand 1 expression remains the most recognized and fully validated predictive biomarker of response to immune checkpoint inhibitors. Other markers such as tumor mutational burden, tumor infiltrating lymphocytes, driver mutations, and other molecular elements of the tumor microenvironment bear the potential to be predictive tools; however, the majority are still investigational. In this review, we describe the advances noted thus far on currently validated as well as novel emerging biomarkers that have the potential to guide the use of immunotherapy agents in the management of non-small cell lung cancer., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Ectopic Cushing syndrome (EAS) secondary to an adrenocorticotropin hormone (ACTH)-releasing neuroendocrine tumor (NET) is a rare diagnosis that can be resistant to standard treatments. Abiraterone acetate (AA) is a selective and irreversible inhibitor of 17α-hydroxylase/17,20-lyase that blocks adrenal steroidogenesis, including cortisol synthesis. In this case, we present the novel use of AA in treating malignant EAS by blocking cortisol synthesis., Case Description: We present a case in which a middle-aged female diagnosed with EAS secondary to metastatic ACTH-releasing NET who presented with progressively worsening weakness, diagnosed with glucocorticoid-induced myopathy associated with autonomic dysregulation. Due to her tenuous clinical status, the patient was not a candidate for any invasive procedures. She was treated with AA which led to a rapid quantitative reduction in the serum cortisol levels and hemodynamic improvement. This temporizing measure allowed for clinical stability, the patient underwent adrenal artery embolization and abiraterone was discontinued. The patient did not experience any further decline in her strength, her symptoms related to myopathy slowly improved, she was discharged to a rehabilitation facility., Conclusions: This case illustrates how the inhibition of cortisol caused by AA can be effectively used in the management of EAS. The potent and rapid effects of AA in blocking endogenous cortisol production may be considered as a temporizing measure in the treatment of malignant EAS., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-22-376/coif). RL has received consulting honoraria from Xcenda and Aptitude health in the past 36 months. The other authors have no conflicts of interest to declare., (2022 Journal of Gastrointestinal Oncology. All rights reserved.)

Large granular lymphocytic (LGL) leukemia is a rare chronic lymphoproliferative disorder that can arise from T- or natural killer-cell lineages. It is an indolent disease that typically occurs in the sixth decade of life. Most cases of T-cell LGL leukemia (T-LGL) are associated with autoimmune disorders. Patients with T-LGL are generally asymptomatic; however, they can present with symptoms related to neutropenia, infections, and autoimmune disorders. Here, we report two cases of T-LGL in which the patients presented with liver dysfunction., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Abu Rous et al.)

Background: Human epidermal growth factor receptor 2 (ERBB2) mutation is a known oncogenic driver mutation in a small proportion of non-small cell lung cancers (NSCLCs). Many targeted therapies are being developed and investigated for the treatment of ERBB2-mutated NSCLC, however none of these agents have yet been approved as a front-line treatment. Thus, platinum-based chemotherapy with or without immunotherapy remains the preferred first-line therapy for ERBB2-mutated NSCLC., Objective: We aimed to study the activity of chemotherapy in combination with pembrolizumab as first-line treatment in patients with stage IV ERBB2-mutated NSCLC., Patients and Methods: We retrospectively identified five patients with ERBB2-mutated NSCLC treated with carboplatin, pemetrexed and pembrolizumab as first-line therapy between 2018 and 2020. Overall survival (OS), progression-free survival (PFS), and time to next therapy (TTNT) were summarized by Kaplan-Meier methodology using R 4.0.5 with median time to event. Response rates defined by partial response (PR) or PR + stable disease (SD) and 95% Clopper-Pearson confidence interval (CI) were calculated., Results: The median age of these five patients was 60 years and all five patients' tumors had ERBB2 mutations-4 had exon 20 mutation and 1 had exon 23 mutation. With a median follow-up of 32 months, the median OS was 24 months, the median PFS was 9 months, and the median TTNT was 9 months. The response rate was 0.6 for PR (Clopper-Pearson exact 95% CI 0.147-0.947) and 0.8 for PR and SD (Clopper-Pearson exact 95% CI 0.284-0.995). No unexpected toxicities were observed., Conclusion: In a small number of patients, chemotherapy and pembrolizumab as first-line therapy in ERBB2-mutated NSCLC patients demonstrated activity similar to previous reports with this regimen. Future clinical trials are needed to determine the role of chemotherapy and immunotherapy for this patient population in the context of emerging targeted agents., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Competing Interests: Competing interests: None declared.

A 57-year-old Southeast Asian woman with a remote history of adenoid cystic carcinoma (ACC) of the right labium superius oris (upper lip) presented to the hospital with vague epigastric pain. On workup, she was found to have multiple pleural nodules. Histopathology confirmed the diagnosis of metastatic ACC. After 8 months of active surveillance, evidence of disease progression was found and the patient was started on pembrolizumab. Follow-up after starting pembrolizumab showed stable disease with no significant side effects., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

A 47-year-old man presented to the emergency department with acute onset of dyspnoea and a week history of painful erythematous rash on both of his legs. CT angiogram of the chest showed saddle pulmonary embolism resulting in right ventricular strain and obstructive shock. Due to the atypical nature of his skin rash, a skin biopsy from one of these lesions was done and came consistent with the diagnosis of IgA vasculitis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Here we describe a 27-year-old woman, 5 months post partum, who presented to the emergency department with bilateral breast masses. She was initially treated as lactational mastitis with no improvement. Breast ultrasound showed bilateral breast and axillary lymphadenopathy suggestive of metastatic/neoplastic process, and chest X-ray showed a large anterior mediastinal mass. Further work-up led to the diagnosis of T-cell acute lymphoblastic leukaemia. The patient was started on a paediatric regimen using the children's oncology group AALL0434 protocol. The patient achieved a complete remission following induction chemotherapy with resolution of her presenting symptoms., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

A 69-year-old woman with a remote history of Graves' disease treated with radioactive iodine ablation, who was maintained on a stable dose of levothyroxine for 15 years, presented with abnormal and fluctuating thyroid function tests which were confusing. After extensive evaluation, no diagnosis could be made, and it became difficult to optimise the levothyroxine dose, until we became aware of the recently recognised biotin-induced lab interference. It was then noticed that her medication list included biotin 10 mg two times per day. After holding the biotin and repeating the thyroid function tests, the labs made more sense, and the patient was easily made euthyroid with appropriate dose adjustment. We also investigated our own laboratory, and identified the thyroid labs that are performed with biotin-containing assays and developed strategies to increase the awareness about this lab artefact in our clinics., Competing Interests: Competing interests: For SA Abbott Diagnostics (Consultant), since October 2019. Related to biotin interference with labs. This COI is recent and it started after we began writing the case up. The company approached SA given his prior published work on biotin.The other authors have no competing interests., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

A 63-year-old woman with a medical history of chronic myelogenous leukaemia treated with dasatinib, chronic obstructive pulmonary disease and heart failure with preserved ejection fraction presented with difficulty in breathing. Chest X-ray showed large right-sided pleural effusion, which was confirmed on a CT angiogram of the chest. Echocardiogram showed an ejection fraction of 61% with moderate to severely dilated right ventricle and right ventricular systolic pressure of 60 mm Hg. Diagnostic and therapeutic thoracentesis was performed, and 2.2 L of pleural fluid was removed. Pleural fluid analysis was consistent with chylothorax. Significant symptomatic improvement was noted after thoracentesis. In the absence of an alternate explanation, chylothorax was attributed to dasatinib, which was switched to nilotinib. This resulted in resolution of her pleural effusions., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.