Non-Small Cell Lung Cancer, Version 4.2024, NCCN Clinical Practice Guidelines in Oncology

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommendations for the treatment of patients with NSCLC, including diagnosis, primary disease management, surveillance for relapse, and subsequent treatment. The panel has updated the list of recommended targeted therapies based on recent FDA approvals and clinical data. This selection from the NCCN Guidelines for NSCLC focuses on treatment recommendations for advanced or metastatic NSCLC with actionable molecular biomarkers.

NCCN Guidelines® Insights: Mesothelioma: Pleural, Version 1.2024.

Mesothelioma is a rare cancer that originates from the mesothelial surfaces of the pleura and other sites, and is estimated to occur in approximately 3,500 people in the United States annually. Pleural mesothelioma is the most common type and represents approximately 85% of these cases. The NCCN Guidelines for Mesothelioma: Pleural provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pleural mesothelioma. These NCCN Guidelines Insights highlight significant updates to the NCCN Guidelines for Mesothelioma: Pleural, including revised guidance on disease classification and systemic therapy options.

Mesothelioma: Peritoneal, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.

Mesothelioma is a rare cancer originating in mesothelial surfaces of the peritoneum, pleura, and other sites. These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) focus on peritoneal mesothelioma (PeM). The NCCN Guidelines for PeM provide recommendations for workup, diagnosis, and treatment of primary as well as previously treated PeM. The diagnosis of PeM may be delayed because PeM mimics other diseases and conditions and because the disease is so rare. The pathology section was recently updated to include new information about markers used to identify mesothelioma, which is difficult to diagnose. The term "malignant" is no longer used to classify mesotheliomas, because all mesotheliomas are now defined as malignant.

NCCN Guidelines® Insights: Non-Small Cell Lung Cancer, Version 2.2023.

The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) provide recommendations for management of disease in patients with NSCLC. These NCCN Guidelines Insights focus on neoadjuvant and adjuvant (also known as perioperative) systemic therapy options for eligible patients with resectable NSCLC.

Non-Small Cell Lung Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommended management for patients with NSCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. Patients with metastatic lung cancer who are eligible for targeted therapies or immunotherapies are now surviving longer. This selection from the NCCN Guidelines for NSCLC focuses on targeted therapies for patients with metastatic NSCLC and actionable mutations.

NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 2.2021.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines regarding targeted therapies, immunotherapies, and their respective biomarkers.

NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 1.2020.

The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates in immunotherapy. For the 2020 update, all of the systemic therapy regimens have been categorized using a new preference stratification system; certain regimens are now recommended as "preferred interventions," whereas others are categorized as either "other recommended interventions" or "useful under certain circumstances."

NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 5.2018.

The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the targeted therapy and immunotherapy sections in the NCCN Guidelines. For the 2018 update, a new section on biomarkers was added.

Model System Identifies Kinetic Driver of Hsp90 Inhibitor Activity against African Trypanosomes and Plasmodium falciparum.

Hsp90 inhibitors, well studied in the laboratory and clinic for antitumor indications, have promising activity against protozoan pathogens, including Trypanosoma brucei which causes African sleeping sickness, and the malaria parasite, Plasmodium falciparum To progress these experimental drugs toward clinical use, we adapted an in vitro dynamic hollow-fiber system and deployed artificial pharmacokinetics to discover the driver of their activity: either concentration or time. The activities of compounds from three major classes of Hsp90 inhibitors in development were evaluated against trypanosomes. In all circumstances, the activities of the tested Hsp90 inhibitors were concentration driven. By optimally deploying the drug to match its kinetic driver, the efficacy of a given dose was improved up to 5-fold, and maximal efficacy was achieved with a significantly lower drug exposure. The superiority of concentration-driven regimens was evident in vitro over several logs of drug exposure and was predictive of efficacy in a mouse model of African trypanosomiasis. In studies with P. falciparum, antimalarial activity was similarly concentration driven. This experimental strategy offers an expedient and versatile translational tool to assess the impact of pharmacokinetics on antiprotozoal activity. Knowing kinetic governance early in drug development provides an additional metric for judging lead compounds and allows the incisive design of animal efficacy studies.

Long-acting injectable atovaquone nanomedicines for malaria prophylaxis.

Chemoprophylaxis is currently the best available prevention from malaria, but its efficacy is compromised by non-adherence to medication. Here we develop a long-acting injectable formulation of atovaquone solid drug nanoparticles that confers long-lived prophylaxis against Plasmodium berghei ANKA malaria in C57BL/6 mice. Protection is obtained at plasma concentrations above 200 ng ml-1 and is causal, attributable to drug activity against liver stage parasites. Parasites that appear after subtherapeutic doses remain atovaquone-sensitive. Pharmacokinetic-pharmacodynamic analysis indicates protection can translate to humans at clinically achievable and safe drug concentrations, potentially offering protection for at least 1 month after a single administration. These findings support the use of long-acting injectable formulations as a new approach for malaria prophylaxis in travellers and for malaria control in the field.

Non-Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) focuses on targeted therapies and immunotherapies for metastatic NSCLC, because therapeutic recommendations are rapidly changing for metastatic disease. For example, new recommendations were added for atezolizumab, ceritinib, osimertinib, and pembrolizumab for the 2017 updates.

NCCN Guidelines Insights: Malignant Pleural Mesothelioma, Version 3.2016.

These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Malignant Pleural Mesothelioma (MPM). These NCCN Guidelines Insights discuss systemic therapy regimens and surgical controversies for MPM. The NCCN panel recommends cisplatin/pemetrexed (category 1) for patients with MPM. The NCCN panel also now recommends bevacizumab/cisplatin/pemetrexed as a first-line therapy option for patients with unresectable MPM who are candidates for bevacizumab. The complete version of the NCCN Guidelines for MPM, available at NCCN.org, addresses all aspects of management for MPM including diagnosis, evaluation, staging, treatment, surveillance, and therapy for recurrence and metastasis; NCCN Guidelines are intended to assist with clinical decision-making.

Hollow-Fiber Methodology for Pharmacokinetic/Pharmacodynamic Studies of Antimalarial Compounds.

Knowledge of pharmacokinetic/pharmacodynamic (PK/PD) relationships can enhance the speed and economy of drug development by enabling informed and rational decisions at every step, from lead selection to clinical dosing. For anti-infective agents in particular, dynamic in vitro hollow-fiber cartridge experiments permit exquisite control of kinetic parameters and the study of their consequent impact on pharmacodynamic efficacy. Such information is of great interest for the cost-restricted but much-needed development of new antimalarial drugs, especially since the major human pathogen Plasmodium falciparum can be cultivated in vitro but is not readily available in animal models. This protocol describes the materials and procedures for determining the PK/PD relationships of antimalarial compounds.

NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 4.2016.

These NCCN Guidelines Insights focus on recent updates in the 2016 NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC; Versions 1-4). These NCCN Guidelines Insights will discuss new immunotherapeutic agents, such as nivolumab and pembrolizumab, for patients with metastatic NSCLC. For the 2016 update, the NCCN panel recommends immune checkpoint inhibitors as preferred agents (in the absence of contraindications) for second-line and beyond (subsequent) therapy in patients with metastatic NSCLC (both squamous and nonsquamous histologies). Nivolumab and pembrolizumab are preferred based on improved overall survival rates, higher response rates, longer duration of response, and fewer adverse events when compared with docetaxel therapy.

Non-Small Cell Lung Cancer, Version 6.2015.

These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC). Appropriate targeted therapy is very effective in patients with advanced NSCLC who have specific genetic alterations. Therefore, it is important to test tumor tissue from patients with advanced NSCLC to determine whether they have genetic alterations that make them candidates for specific targeted therapies. These NCCN Guidelines Insights describe the different testing methods currently available for determining whether patients have genetic alterations in the 2 most commonly actionable genetic alterations, notably anaplastic lymphoma kinase (ALK) gene rearrangements and sensitizing epidermal growth factor receptor (EGFR) mutations.

Non-small cell lung cancer, version 1.2015.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) focuses on the principles of radiation therapy (RT), which include the following: (1) general principles for early-stage, locally advanced, and advanced/metastatic NSCLC; (2) target volumes, prescription doses, and normal tissue dose constraints for early-stage, locally advanced, and advanced/palliative RT; and (3) RT simulation, planning, and delivery. Treatment recommendations should be made by a multidisciplinary team, including board-certified radiation oncologists who perform lung cancer RT as a prominent part of their practice.

Non-small cell lung cancer, version 2.2013.

These NCCN Guidelines Insights focus on the diagnostic evaluation of suspected lung cancer. This topic was the subject of a major update in the 2013 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer. The NCCN Guidelines Insights focus on the major updates in the NCCN Guidelines and discuss the new updates in greater detail.

Thymomas and thymic carcinomas: Clinical Practice Guidelines in Oncology.

Masses in the anterior mediastinum can be neoplasms (eg, thymomas, thymic carcinomas, or lung metastases) or non-neoplastic conditions (eg, intrathoracic goiter). Thymomas are the most common primary tumor in the anterior mediastinum, although they are rare. Thymic carcinomas are very rare. Thymomas and thymic carcinomas originate in the thymus. Although thymomas can spread locally, they are much less invasive than thymic carcinomas. Patients with thymomas have 5-year survival rates of approximately 78%. However, 5-year survival rates for thymic carcinomas are only approximately 40%. These guidelines outline the evaluation, treatment, and management of these mediastinal tumors.

Protection of humans by plant glucosinolates: efficiency of conversion of glucosinolates to isothiocyanates by the gastrointestinal microflora.

Plant-based diets rich in crucifers are effective in preventing cancer and other chronic diseases. Crucifers contain very high concentrations of glucosinolates (GS; ß-thioglucoside-N-hydroxysulfates). Although not themselves protective, GS are converted by coexisting myrosinases to bitter isothiocyanates (ITC) which defend plants against predators. Coincidentally, ITC also induce mammalian genes that regulate defenses against oxidative stress, inflammation, and DNA-damaging electrophiles. Consequently, the efficiency of conversion of GS to ITC may be critical in controlling the health-promoting benefits of crucifers. If myrosinase is heat-inactivated by cooking, the gastrointestinal microflora converts GS to ITC, a process abolished by enteric antibiotics and bowel cleansing. When single oral doses of GS were administered as broccoli sprout extracts (BSE) to two dissimilar populations (rural Han Chinese and racially mixed Baltimoreans) patterns of excretions of urinary dithiocarbamates (DTC) were very similar. Individual conversions in both populations varied enormously, from about 1% to more than 40% of dose. In contrast, administration of ITC (largely sulforaphane)-containing BSE resulted in uniformly high (70%-90%) conversions to urinary DTC. Despite the remarkably large range of conversion efficiencies between individuals, repeated determinations within individuals were much more consistent. The rates of urinary excretion (slow or fast) were unrelated to the ultimate magnitudes (low or high) of these conversions. Although no demographic factors affecting conversion efficiency have been identified, there are clearly diurnal variations: conversion of GS to DTC was greater during the day, but conversion of ITC to DTC was more efficient at night.

Malaria-infected mice are cured by a single oral dose of new dimeric trioxane sulfones which are also selectively and powerfully cytotoxic to cancer cells.

A new series of 6 dimeric trioxane sulfones has been prepared from the natural trioxane artemisinin in five or six chemical steps. One of these thermally and hydrolytically stable new chemical entities (4c) completely cured malaria-infected mice via a single oral dose of 144 mg/kg. At a much lower single oral dose of only 54 mg/kg combined with 13 mg/kg of mefloquine hydrochloride, this trioxane dimer 4c as well as its parent trioxane dimer 4b also completely cured malaria-infected mice. Both dimers 4c and 4b were potently and selectively cytotoxic toward five cancer cell lines.