Chondrosarcoma With Pulmonary Metastatic Calcifications: A Case Report and Review of the Literature.

A chondrosarcoma with pulmonary metastatic calcifications is a rarely reported phenomenon. This report discusses chondrosarcomas and their clinical features, diagnosis, and treatment, using as an example the case of a 55-year-old female with a right pelvic chondrosarcoma that developed over 10 years. In the last two years, the patient had increasing pulmonary findings, including pulmonary nodules, ground glass opacities, and likely pulmonary metastatic calcifications. The objective of this report is to explore chondrosarcomas and their pattern of metastatic presentation, with the hope of improving recognition of the disease and streamlining treatment.

Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update.

PURPOSE: To update an evidence-based guideline to assist in clinical decision-making for patients with advanced hepatocellular carcinoma (HCC). METHODS: ASCO convened an Expert Panel to update the 2020 guideline on systemic therapy for HCC. The panel updated the systematic review to include randomized controlled trials (RCTs) published through October 2023 and updated recommendations. RESULTS: Ten new RCTs met the inclusion criteria and were added to the evidence base. RECOMMENDATIONS: Atezolizumab + bevacizumab (atezo + bev) or durvalumab + tremelimumab (durva + treme) may be offered first-line for patients with advanced HCC, Child-Pugh class A liver disease, and Eastern Cooperative Oncology Group performance status 0-1. Where there are contraindications to these therapies, sorafenib, lenvatinib, or durvalumab may be offered first-line. Following first-line treatment with atezo + bev, second-line therapy with a tyrosine kinase inhibitor (TKI), ramucirumab (for patients with alpha-fetoprotein [AFP] ≥400 ng/mL), durva + treme, or nivolumab + ipilimumab (nivo + ipi) may be recommended for appropriate candidates. Following first-line therapy with durva + treme, second-line therapy with a TKI is recommended. Following first-line treatment with sorafenib or lenvatinib, second-line therapy options include cabozantinib, regorafenib for patients who previously tolerated sorafenib, ramucirumab (AFP ≥400 ng/mL), nivo + ipi, or durvalumab; atezo + bev or durva + treme may be considered for patients who did not have access to these therapies in the first-line setting, and do not have contraindications. Pembrolizumab or nivolumab are also options for appropriate patients following sorafenib or lenvatinib. Third-line therapy may be considered in Child-Pugh class A patients with good PS, using one of the agents listed previously that has a nonidentical mechanism of action with previously received therapy. A cautious approach to systemic therapy is recommended for patients with Child-Pugh class B advanced HCC. Further guidance on choosing between options is included within the guideline.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.

An aggressive case of a thoracic undifferentiated SMARCA4-deficient tumor with extensive pleural involvement.

SMARCA4-deficient undifferentiated thoracic tumors are a rare phenomenon. A 40-year-old male was newly diagnosed with SMARCA4-deficient undifferentiated non-small cell lung cancer. He had a history of heavy smoking and job-related exposure to metal dust and melted nickel. CT imaging showed numerous right-sided pleural masses and soft tissue plaques, but no metastases. CT-guided biopsy of a pleural mass confirmed the diagnosis. He was prescribed six cycles of carboplatin paclitaxel, and follow-up imaging showed largely stable disease. Treatment was changed to nivolumab due to shortness of breath, and he received one cycle of nivolumab without considerable side effects. Unfortunately, during the second cycle of his nivolumab, the patient presented with new weakness. Imaging showed spinal cord metastasis and he underwent a laminectomy; he was subsequently followed up as an outpatient. The objective of this publication was to explore SMARCA4-deficient undifferentiated thoracic tumors, other related SMARCA4-deficient tumors, and their overall pattern of presentation. The genetic aberrations of this case are compared to recent publications that also discuss genetic aberrations commonly occurring with this disease process, with an ultimate goal of hastening detection and adding to the library of treatment results.

Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2023.3.

PURPOSE: To provide evidence-based recommendations for patients with stage IV non-small cell lung cancer with driver alterations. METHODS: This ASCO living guideline offers continually updated recommendations based on an ongoing systematic review of randomized clinical trials (RCTs), with the latest time frame spanning February to October 2023. An Expert Panel of medical oncology, pulmonary, community oncology, research methodology, and advocacy experts were convened. The literature search included systematic reviews, meta-analyses, and randomized controlled trials. Outcomes of interest include efficacy and safety. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS: This guideline consolidates all previous updates and reflects the body of evidence informing this guideline topic. Eight new RCTs were identified in the latest search of the literature to date. RECOMMENDATIONS: Evidence-based recommendations were updated to address first, second, and subsequent treatment options for patients based on targetable driver alterations.Additional information is available at www.asco.org/living-guidelines.

Therapy for Stage IV Non-Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2023.3.

PURPOSE: To provide evidence-based recommendations for patients with stage IV non-small cell lung cancer (NSCLC) without driver alterations. METHODS: This ASCO living guideline offers continually updated recommendations based on an ongoing systematic review of randomized clinical trials (RCTs), with the latest time frame spanning February to October 2023. An Expert Panel of medical oncology, pulmonary, community oncology, research methodology, and advocacy experts were convened. The literature search included systematic reviews, meta-analyses, and randomized controlled trials. Outcomes of interest include efficacy and safety. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS: This guideline consolidates all previous updates and reflects the body of evidence informing this guideline topic. Ten new RCTs were identified in the latest search of the literature to date. RECOMMENDATIONS: Evidence-based recommendations were updated to address first, second, and subsequent treatment options for patients without driver alterations.Additional information is available at www.asco.org/living-guidelines.

Bispecific Antibodies in Lung Cancer: A State-of-the-Art Review.

Bispecific antibodies have emerged as a promising class of therapeutics in the field of oncology, offering an innovative approach to target cancer cells while sparing healthy tissues. These antibodies are designed to bind two different antigens, enabling them to bridge immune cells with cancer cells, resulting in enhanced tumor cell killing and improved treatment responses. This review article summarizes the current landscape of bispecific antibodies in lung cancer, including their mechanisms of action, clinical development, and potential applications in other solid tumor malignancies. Additionally, the challenges and opportunities associated with their use in the clinic are discussed, along with future directions for research and development in this exciting area of cancer immunotherapy.

Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2023.2.

Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in 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 provider and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix 1 and Appendix 2). Updates are published regularly and can be found at https://ascopubs.org/nsclc-da-living-guideline.

Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2023.1.

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 provider and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix 1 and Appendix 2). Updates are published regularly and can be found at https://ascopubs.org/nsclc-da-living-guideline.

Therapy for Stage IV Non-Small-Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2023.1.

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 provider and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix 1 and Appendix 2). Updates are published regularly and can be found at https://ascopubs.org/nsclc-non-da-living-guideline.

Impact of P16 Positivity on Clinical Outcomes in Nasopharyngeal Carcinoma: A Single Institution Study.

Introduction Nasopharyngeal carcinoma (NPC) is a rare malignancy with unique geographical distribution. It is prevalent in East and Southeast Asia and rare in non-endemic countries like the USA. P16 is a tumor suppressor gene and there are limited studies with inconsistent results describing the association of its positivity in immunohistochemistry and clinical outcomes. In this retrospective study, we compared progression-free survival (PFS) and overall survival (OS) based on p16 positivity in 60 patients with NPC. Materials and methods Patients aged above 18 years and followed between July 2015 and December 2020 were included in the study. P16 positivity was based on the immunohistochemistry of the biopsy sample. We compared PFS and OS among all p16-positive and negative patients, and then among patients with advanced disease (stage III or IV), and between p16-positive, negative, and unknown status patients. Results There were 15 p16-positive, and 28 p16-negative, with a median age of 54.3 years and 55.7 years respectively. Most patients in both groups were male, Caucasian, and had advanced disease (stage III or stage IV). Both median PFS (p=0.838) and OS (p=0.776) were 84 months in the p16-negative group but were not reached during the study period in the p16-positive group. Among advanced-stage patients, the PFS (p=0.873), and OS (p=0.773) of both groups were not statistically significant. P16 status was unknown for 17 patients, and PFS (p=0.785) and OS (p=0.901), when compared among patients with p16-positive, negative, and unknown status, were also statistically non-significant. Discussion and conclusion Our analysis suggests that p16 status does not predict clinical outcomes in NPC patients. Our sample size was limited but is larger than most studies describing this association. With different studies in the literature reporting disparate findings, we recommend larger prospective studies to better illustrate the impact of p16 positivity on clinical outcomes in NPC.

Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2022.3.

Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in 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 provider and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix 1 and Appendix 2). Updates are published regularly and can be found at https://ascopubs.org/nsclc-da-living-guideline.

Therapy for Stage IV Non-Small-Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2022.3.

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 provider and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix 1 and Appendix 2). Updates are published regularly and can be found at https://ascopubs.org/nsclc-non-da-living-guideline.

Therapy for Stage IV Non-Small-Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2022.2.

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 provider and do not account for individual variation among patients. See Appendix 1 (online only) for disclaimers and other important information. Updates are published regularly and can be found at https://ascopubs.org/nsclc-non-da-living-guideline.

Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2022.2.

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 provider and do not account for individual variation among patients. See Appendix 1 (online only) for disclaimers and other important information. Updates are published regularly and can be found at https://ascopubs.org/nsclc-da-living-guideline.

Treatment of Metastatic Colorectal Cancer: ASCO Guideline.

PURPOSE: To develop recommendations for treatment of patients with metastatic colorectal cancer (mCRC). METHODS: ASCO convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice. RESULTS: Five systematic reviews and 10 randomized controlled trials met the systematic review inclusion criteria. RECOMMENDATIONS: Doublet chemotherapy should be offered, or triplet therapy may be offered to patients with previously untreated, initially unresectable mCRC, on the basis of included studies of chemotherapy in combination with anti-vascular endothelial growth factor antibodies. In the first-line setting, pembrolizumab is recommended for patients with mCRC and microsatellite instability-high or deficient mismatch repair tumors; chemotherapy and anti-epidermal growth factor receptor therapy is recommended for microsatellite stable or proficient mismatch repair left-sided treatment-naive RAS wild-type mCRC; chemotherapy and anti-vascular endothelial growth factor therapy is recommended for microsatellite stable or proficient mismatch repair RAS wild-type right-sided mCRC. Encorafenib plus cetuximab is recommended for patients with previously treated BRAF V600E-mutant mCRC that has progressed after at least one previous line of therapy. Cytoreductive surgery plus systemic chemotherapy may be recommended for selected patients with colorectal peritoneal metastases; however, the addition of hyperthermic intraperitoneal chemotherapy is not recommended. Stereotactic body radiation therapy may be recommended following systemic therapy for patients with oligometastases of the liver who are not considered candidates for resection. Selective internal radiation therapy is not routinely recommended for patients with unilobar or bilobar metastases of the liver. Perioperative chemotherapy or surgery alone should be offered to patients with mCRC who are candidates for potentially curative resection of liver metastases. Multidisciplinary team management and shared decision making are recommended. Qualifying statements with further details related to implementation of guideline recommendations are also included.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.

Cardiotoxicity of Biological Therapies in Cancer Patients: An In-depth Review.

Cardiotoxicity from chemotherapy regimens has been long reported. However, the understanding of cardiac side effects of biological therapies is rapidly evolving. With cancer patients achieving higher life expectancy due to the use of personalized medicine and novel targeted anticancer agents, the occurrence of cardiotoxicity is becoming more significant. Novel biological therapies include anti-HER2 antibodies, tyrosine kinase inhibitors, bruton kinase inhibitors, antivascular endothelial growth factors, proteasome inhibitors, immunomodulator drugs, and immune checkpoint inhibitors. Potential cardiovascular toxicities linked to these anticancer agents include hypertension, arrhythmias, QT prolongation, myocardial ischemia and infarction, left ventricular dysfunction, congestive heart failure, and thromboembolism. Cardiac biomarkers, electrocardiography, echocardiography and magnetic resonance imaging are common diagnostic modalities used for early detection of these complications and timely intervention. This review discusses the various types of cardiotoxicities caused by novel anticancer biologic agents, their molecular and pathophysiological mechanisms, risk factors, and diagnostic and management strategies that can be used to prevent, minimize, and treat them.

Therapeutic landscape of advanced HER2-positive breast cancer in 2022.

HER2-positive breast cancer is an aggressive subtype of breast cancer with five-year survival rates of 30% for the advanced stage. The development of anti-HER2 treatments has led to a paradigm shift in the management and clinical outcomes of advanced HER2-positive breast cancer patients. The standard first-line treatment consists of taxane-based chemotherapy plus dual anti-HER2 therapies with trastuzumab and pertuzumab. The antibody-drug conjugate (ADC) ado-trastuzumab emtansine (T-DM1) has been a second-line therapeutic standard, but the second-line treatment approach is rapidly evolving. Given a substantial advantage of another ADC, Fam-trastuzumab deruxtecan (T-DXd), compared to T-DM1 in a recent randomized trial in the second-line setting, T-DXd is currently the preferred second-line option. Optimal third-line treatment strategies are still not established, and multiple approaches have been used including combinations based on capecitabine, trastuzumab, or both with oral anti-HER2 tyrosine kinase inhibitors. Tucatinib plus capecitabine and trastuzumab, lapatinib plus trastuzumab, neratinib or lapatinib plus capecitabine are some of the FDA approved combinations. Another newer agent approved for third- or later-line therapy in the metastatic setting is margetuximab, an Fc-engineered anti-HER2 monoclonal antibody, in combination with chemotherapy. Other novel agents currently under clinical trials are the drugs that indirectly target HER2, including immune cell cycle inhibitors, PI3K/mTOR inhibitors, and immunotherapy agents.