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.

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 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 2022.2.

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.

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

PURPOSE: To provide evidence-based recommendations updating the 2021 ASCO and Ontario Health (Cancer Care Ontario) guideline on systemic therapy for patients with stage IV non-small-cell lung cancer (NSCLC) with driver alterations. METHODS: ASCO updated recommendations on the basis of an ongoing systematic review of randomized control trials from 2020 to 2021. RESULTS: This guideline update reflects changes in evidence since the previous update. Two studies provide the evidence base. Outcomes of interest include efficacy and safety. RECOMMENDATIONS: For patients with an anaplastic lymphoma kinase rearrangement, a performance status (PS) of 0-2, and previously untreated NSCLC, clinicians should offer alectinib or brigatinib or lorlatinib. For patients with an anaplastic lymphoma kinase rearrangement, a PS of 0-2, and previously untreated NSCLC, if alectinib, brigatinib, or lorlatinib are not available, clinicians should offer ceritinib or crizotinib. For patients with a RET rearrangement, a PS of 0-2, and previously untreated NSCLC, clinicians may offer selpercatinib or pralsetinib. In second line, for patients with a RET rearrangement who have not received RET-targeted therapy, clinicians may offer selpercatinib or pralsetinib.Additional information is available at www.asco.org/thoracic-cancer-guidelines.

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

PURPOSE: To provide evidence-based recommendations updating the 2020 ASCO and Ontario Health (Cancer Care Ontario) guideline on systemic therapy for patients with stage IV non-small-cell lung cancer without driver alterations. METHODS: ASCO updated recommendations on the basis of an ongoing systematic review of randomized clinical trials from 2018 to 2021. RESULTS: This guideline update reflects changes in evidence since the previous update. Five randomized clinical trials provide the evidence base. Outcomes of interest include efficacy and safety. RECOMMENDATIONS: In addition to 2020 options for patients with high programmed death ligand-1 (PD-L1) expression (tumor proportion score [TPS] ≥ 50%), nonsquamous cell carcinoma (non-SCC), and performance status (PS) 0-1, clinicians may offer single-agent atezolizumab. With high PD-L1 expression (TPS ≥ 50%), non-SCC, and PS 0-1, clinicians may offer nivolumab and ipilumumab alone or nivolumab and ipilimumab plus chemotherapy. With negative (0%) and low positive PD-L1 expression (TPS 1%-49%), non-SCC, and PS 0-1, clinicians may offer nivolumab and ipilimumab alone or nivolumab and ipilimumab plus chemotherapy. With high PD-L1 expression, SCC, and PS 0-1, clinicians may offer single-agent atezolizumab. With high PD-L1 expression, squamous cell carcinoma (SCC), and PS 0-1, clinicians may offer nivolumab and ipilimumab alone or in combination with two cycles of platinum-based chemotherapy. With negative and low positive PD-L1 expression, SCC, and PS 0-1, clinicians may offer nivolumab and ipilimumab alone or in combination with two cycles of platinum-based chemotherapy. With non-SCC who received an immune checkpoint inhibitor and chemotherapy as first-line therapy, clinicians may offer second-line paclitaxel plus bevacizumab. With non-SCC, who received chemotherapy with or without bevacizumab and immune checkpoint inhibitor therapy, clinicians should offer the options of third-line single-agent pemetrexed, docetaxel, or paclitaxel plus bevacizumab.Additional information is available at www.asco.org/thoracic-cancer-guidelines.

Effectiveness of a Smartwatch App in Detecting Induced Falls: Observational Study.

BACKGROUND: Older adults are at an increased risk of falls with the consequent impacts on the health of the individual and health expenditure for the population. Smartwatch apps have been developed to detect a fall, but their sensitivity and specificity have not been subjected to blinded assessment nor have the factors that influence the effectiveness of fall detection been fully identified. OBJECTIVE: This study aims to assess accuracy metrics for a novel fall detection smartwatch algorithm. METHODS: We performed a cross-sectional study of 22 healthy adults comparing the detection of induced forward, side (left and right), and backward falls and near falls provided by a smartwatch threshold-based algorithm, with a video record of induced falls serving as the gold standard; a blinded assessor compared the two. Three different smartwatches with two different operating systems were used. There were 226 falls: 64 were backward, 51 forward, 55 left sided, and 56 right sided. RESULTS: The overall smartwatch app sensitivity for falls was 77%, the specificity was 99%, the false-positive rate was 1.7%, and the false-negative rate was 16.4%. The positive and negative predictive values were 98% and 84%, respectively, while the accuracy was 89%. There were 249 near falls: the sensitivity was 89%, the specificity was 100%, there were no false positives, 11% were false negatives, the positive predictive value was 100%, the false-negative predictive value was 83%, and the accuracy was 93%. CONCLUSIONS: Falls were more likely to be detected if the fall was on the same side as the wrist with the smartwatch. There was a trend toward some smartwatches and operating systems having superior sensitivity, but these did not reach statistical significance. The effectiveness data and modifying factors pertaining to this smartwatch app can serve as a reference point for other similar smartwatch apps.

A Randomized, Single-Blind Study Evaluating the Effect of a Bone Pain Education Video on Reported Bone Pain in Patients with Breast Cancer Receiving Chemotherapy and Pegfilgrastim.

BACKGROUND: Mild-to-moderate bone pain is the most commonly reported adverse event associated with pegfilgrastim. AIMS: To investigate the effect of bone pain education on pegfilgrastim-related bone pain in patients with breast cancer receiving chemotherapy and pegfilgrastim. DESIGN: Randomized, single-blind study. SETTINGS: Forty-eight community oncology clinics throughout the United States. PARTICIPANTS: Three hundred women ≥18 years of age with newly diagnosed stage I -III breast cancer, who were planning ≥4 cycles of neoadjuvant or adjuvant chemotherapy with pegfilgrastim support starting in cycle 1. METHODS: Patients were randomized 1:1 to view a general education DVD on chemotherapy side effects (GE-DVD) or a DVD on bone pain following chemotherapy and pegfilgrastim (BP-DVD). Patients recorded severity of bone pain on a scale of 0-10, location of pain, and use of bone pain medications (i.e., analgesics, antihistamines, and nonsteroidal anti-inflammatory drugs) for 5 days, beginning on the day of pegfilgrastim administration, in each of the first four chemotherapy cycles. RESULTS: Patient-reported maximum bone pain was similar in the two groups (GE-DVD vs BP-DVD: cycle 1, 3.2 vs. 3.5, p = .3479; across all cycles, 4.1 vs. 4.6, p = .2196). Other measures of bone pain were also similar between the groups. Bone pain was highest in cycle 1 but decreased and then remained stable in subsequent cycles. Bone pain medication use was similar in both groups and was highest in cycle 1. CONCLUSIONS: The bone pain-specific education evaluated here did not improve perceptions of bone pain reported in this patient population.

Complete response to thalidomide and dexamethasone in a patient with necrobiotic xanthogranuloma associated with monoclonal gammopathy: a case report and review of the literature.

Necrobiotic xanthogranuloma (NXG) was first described in 1980 by Kossard and Winkelmann in an article in which they discussed 8 patients with xanthomatous plaques who were noted to have monoclonal gammopathy, predominantly of the Ig(immunoglobulin)G-κ type.(1) Since then more than 50 patients with this disorder have been described, with approximately 80% of them having an associated monoclonal gammopathy. We describe the first case, to our knowledge, of NXG with associated monoclonal gammopathy treated with thalidomide plus dexamethasone, achieving complete resolution of the skin lesions and sustaining response more than 3 years after treatment.

Comparison of platinum-based chemotherapy in patients older and younger than 70 years: an analysis of Southwest Oncology Group Trials 9308 and 9509.

PURPOSE: This retrospective analysis sought to investigate the safety, feasibility, and outcomes of platinum doublet therapy in patients aged 70 years or older with advanced non-small cell lung cancer compared with patients younger than 70 years who participated in two randomized phase III trials conducted by the Southwest Oncology Group. PATIENTS AND METHODS: Outcomes and toxicity data from fit patients with stage IIIB or stage IV non-small cell lung cancer treated with cisplatin/vinorelbine and carboplatin/paclitaxel were pooled from Southwest Oncology Group trials 9308 (S9308) and 9509 (S9509) and compared with respect to age. RESULTS: A total of 616 patients were available for efficacy analyses, of which 122 (20%) were aged 70 years or older. The median progression-free survival was 4 months in both age groups (p = 0.71), and response rates were similar. Overall survival was significantly higher in the younger patient cohort (median 9 months versus 7 months, p = 0.04). Individual parameters of toxicity were similar in both age groups. CONCLUSION: Although patients aged 70 years or older derived initial benefit from platinum-based therapy, survival was better in younger patients. Additional studies in this growing patient population are needed to develop treatment strategies that minimize toxicity and increase efficacy.

Acquired hemophilia as the cause of life-threatening hemorrhage in a 94-year-old man: a case report.

INTRODUCTION: Acquired factor VIII deficiency is a rare entity that can lead to severe and life-threatening bleeding. We describe a case of severe bleeding from the tongue secondary to acquired hemophilia and discuss treatment options, including aminocaproic acid and recombinant factor VIII, which have not been widely reported in the literature for the management of such patients. CASE PRESENTATION: A 94-year-old Caucasian man presented to our institution with diffuse bruising and extensive bleeding from the tongue secondary to mechanical trauma. He had no prior history of bleeding and his medical history was unremarkable except for dementia and hypertension. Coagulation studies revealed a prolonged activated partial thromboplastin time and a mixing study was consistent with the presence of an inhibitor. Quantitative assays revealed a reduced level of factor VIII activity (1%) and the presence of a factor VIII inhibitor, measured at seven Bethesda units, in the serum. Oral prednisone therapy (60mg/day) was given. He also received intravenous aminocaproic acid and human concentrate of factor VIII (Humate-P) and topical anti-thrombolytic agents (100 units of topical thrombin cream). His hospital course was prolonged because of persistent bleeding and the development of profuse melena. He required eight units of packed red blood cells for transfusion. Hospitalization was also complicated by bradycardia of unclear etiology, which started after infusion of aminocaproic acid. His activated partial thromboplastin time gradually normalized. He was discharged to a rehabilitation facility three weeks later with improving symptoms, stable hematocrit and resolving bruises. CONCLUSIONS: Clinicians should suspect a diagnosis of acquired hemophilia in older patients with unexplained persistent and profound bleeding from uncommon soft tissues, including the tongue. Use of factor VIII (Humate-P) and aminocaproic acid can be useful in this coagulopathy but clinicians should be aware of possible life-threatening side effects in older patients, including bradycardia.

Lung cancer in octogenarians.

BACKGROUND: Lung cancer has progressively become a disease of older people, with the median age at diagnosis now exceeding 70 years. Octogenarians represent a rapidly growing proportion of patients diagnosed with lung cancer and can present distinct challenges. Nevertheless, current literature that has set the evidence-based standards of care in this disease does not include significant numbers of patients older than 80 years. METHODS: We have compiled and reviewed the available literature on the specific management and treatment of lung cancer in patients older than 80 years. RESULTS: Retrospective series suggest that surgery is safe and effective in treating early-stage non-small cell lung cancer in selected patients older than 80 years. There is minimal data to support the use of adjuvant chemotherapy in this group. In addition, no data exist on the use of combined chemotherapy and radiotherapy for locally advanced disease. In advanced or metastatic disease, similar to younger elderly populations, single-agent chemotherapy is feasible and seems to offer benefit in terms of symptoms and outcomes. Small cell lung cancer in this population is not well characterized, but small studies suggest symptom improvement and prolongation of survival with the use of chemotherapy. CONCLUSION: Based on retrospective series, octogenarians with lung cancer can derive benefit from many of the treatment modalities used for younger patients including surgery for early-stage disease and single-agent chemotherapy for advanced disease. More elderly specific trials are needed to better refine treatment decisions and improve the care of lung cancer in this group.

Permanent chemotherapy-induced alopecia: case report and review of the literature.

Reversible alopecia following chemotherapy is well recognized and typically not evaluated by dermatologists. However, there are an increasing number of reports of permanent chemotherapy-induced alopecia, typically following high-dose chemotherapy and subsequent bone marrow transplantation. We describe an unusual case of permanent alopecia in a patient who received adjuvant chemotherapy for breast carcinoma, and not a conditioning regimen before bone marrow transplantation. A unique histologic finding of replacement of anagen hair follicles by linear columns of basaloid epithelium is reported. We review the clinical and histologic findings of permanent chemotherapy-induced alopecia and speculate on its pathogenesis.

Dysfunctional T regulatory cells in multiple myeloma.

Multiple myeloma (MM) is characterized by the production of monoclonal immunoglobulin and is associated with suppressed uninvolved immunoglobulins and dysfunctional T-cell responses. The biologic basis of this dysfunction remains ill defined. Because T regulatory (T(reg)) cells play an important role in suppressing normal immune responses, we evaluated the potential role of T(reg) cells in immune dysfunction in MM. We observed a significant increase in CD4+ CD25+ T cells in patients with monoclonal gammopathy of undetermined significance (MGUS) and in patients with MM compared with healthy donors (25% and 26%, respectively, vs 14%); however, T(reg) cells as measured by FOXP3 expression are significantly decreased in patients with MGUS and MM compared with healthy donors. Moreover, even when they are added in higher proportions, T(reg) cells in patients with MM and MGUS are unable to suppress anti-CD3-mediated T-cell proliferation. This decreased number and function of T(reg) cells in MGUS and in MM may account, at least in part, for the nonspecific increase in CD4+ CD25+ T cells, thereby contributing to dysfunctional T-cell responses.