Modern Thoracic Oncology

The following sections are included:

• Foreword
• Contents
• List of Contributors

Embryogenesis involves cellular transformations, differentiation of germ layer cell lineages with specialized genetic and molecular characteristics, and establishment of functional anatomical relationships, all of which are relevant to later neoplasia, tumorigenesis, metastasis, treatment, and prognosis. In this brief overview of the development of the thoracic viscera and walls, we will concentrate primarily on basic cellular and tissue morphogenesis.

Identifying patients who are candidates for surgical resection is especially meaningful in localized lung cancer, as surgery confers the greatest opportunity for cure. Physicians tasked with pre-operative evaluation must include both a perioperative mortality risk assessment as well as a prediction of post-operative lung function in order to optimally counsel patients on anticipated outcomes…

The following sections are included:

• Introduction
• Cardiotoxicity of Cancer Therapies: Implications of Chemotherapy and Radiation
• Cardiac Assessment Prior to Surgical Therapy
• Pre-Operative Evaluation: Cardiac Risk Factors and Functional Status
• Pre-operative Coronary Revascularization: Indications and Management
• Perioperative Cardiac Medication Management
• References

The following sections are included:

• Introduction
• Geriatric Assessment of Cancer Patients
• Assessment of Older Patients Needing Surgery
• References

Chest radiographs are currently obtained using digital techniques and are typically interpreted on Picture Archiving and Communication Systems (PACS) capable of different types of image manipulation. Because of their low cost and wide availability, chest radiographs continue to have an important role in the practice of thoracic oncology, often in the initial assessment of a patient or in the evaluation of non-specific respiratory complaints, such as dyspnea, cough, or chest pain. Radiographs have only moderate sensitivity and specificity for the diagnosis of many important abnormalities associated with intrathoracic neoplasms. They are of limited value in the staging of patients with a known malignancy or in follow-up after treatment, though they have value in the immediate post-operative period. Radiographs may also be used in assessing the size of malignant pleural effusions, including after drainage…

Computed tomography (CT) is the single most important imaging study in the evaluation of thoracic oncology patients. Current CT scanners allow for complete volumetric imaging of the chest during a single breath hold and with a low radiation dose. Chest CT is commonly ordered to further assess an abnormality detected on a chest radiograph. Chest CT is also commonly ordered without a preceding chest radiograph when a patient’s presenting symptoms are acute, severe, or confer a sufficiently high pretest probability for malignant or non-malignant disease. The National Lung Screening Trial (NLST) has demonstrated that low-dose Chest CT can be used to screen for lung cancer in high-risk patients resulting in a reduction in overall and lung cancer mortality. Lung cancer screening will be covered in a dedicated section later in this text…

Positron emission tomography (PET) is a modality that images the radiation resulting from the decay of positron-emitting radiotracers. Emitted positrons collide with neighboring electrons, resulting in the annihilation of both, and the production of two high-energy photons that travel in opposite directions. The photons that escape the body can be detected by the scintillation crystals in PET cameras. The positron emitter most readily available and well-suited to imaging is Fluorine-18 (F-18). F-18 can be attached to a variety of compounds, though glucose is most commonly employed, resulting in the radiotracer 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG). Approximately one hour after injection, PET images are acquired of the whole body or the whole body excluding the very top of the head and the legs. The images that result reveal the distribution of the labeled glucose in the body, including locations of physiologic metabolism (e.g., the brain), areas of FDG accumulation (e.g., the urine) and in abnormalities with high-level metabolism (e.g., tumors)…

The role of magnetic resonant imaging (MRI) in the assessment of thoracic malignancies has become more established over the past decade. MRI benefits from excellent tissue contrast, multiplanar tissue acquisition, dynamic assessment of blood flow, differentiation of tumor from other abnormal tissue with diffusion imaging, and lack of ionizing radiation. However, the application of MRI in intrinsic lung disease has been limited by signal distortion induced from breathing, lack of protons in the lung parenchyma, and magnetic field inhomogeneity. These limitations are yet to be overcome by improved pulse sequences less sensitive to breathing and improved hardware. The current indications for use of MRI in thoracic malignancies include characterization and staging of mediastinal tumors, pleural tumors, chest wall tumors, and superior sulcus tumors; functional assessment of diaphragm; and assessment of pulmonary vasculature and cardiac function in preparation for surgery.

Ultrasound is a commonly used imaging modality that relies on the reflection of sound waves in tissue to generate images. Hand-held surface ultrasound has few uses in thoracic oncology, however. The modality can be used to assess pleural and pericardial effusions, both malignant and benign, and can be used to guide procedures such as thoracentesis, pleural drainage catheter placements, and biopsies of chest wall and pleural masses. Axillary and supraclavicular lymph nodes can be evaluated by ultrasound, and ultrasound can be used to guide biopsies of lymph node in these regions, though CT is generally preferred to assess for lymphadenopathy given its ability to evaluate all of the thoracic lymph node stations…

The imaging, biopsies, and other examinations which comprise a “complete” initial staging vary by tumor type, and indeed, sometimes vary from patient to patient who have the same tumor type. The components of a “standard” initial staging for each individual tumor type will be discussed in subsequent chapters. Below are the general principles that guide the use of imaging in assessing tumor stage and determining when additional workup is needed…

Choosing surgery for the patient with non-small cell lung cancer (NSCLC) and determining the extent of resection most appropriate for cure of the disease and preservation of the patient’s functionality have been important points of discussion over the years. The first intentional thoracotomy and resection of lung tissue was performed by the rural Georgia physician Milton Antony in 1821 to manage what was probably a necrotic lung cancer with extensive anterior chest wall invasion. Anesthesia for this event was accomplished with little more than alcohol intoxication; however, the patient survived the operative intervention and for several months after…

Critical to the diagnosis, staging, and treatment of lung cancer is a complete understanding of thoracic pulmonary anatomy including the intralobar, hilar, and mediastinal lymph nodes. Pulmonary nodal drainage has been well described in clinical pathological studies, and formal international nomenclature for universal identification of the thoracic nodal stations are described and adopted by the International Association for the Study of Lung Cancer (IASLC) and the American Joint Committee on Cancer (AJCC). Deslauriers and colleagues provide an anatomic summary of the entire nodal thoracic lymphatic system that is a key primer and compilation for understanding lymphatic anatomy and ultimately dissection for thoracic malignancies. The nodal stations and zones are essential knowledge for any physician taking care of patients with lung cancer, and can be found in the AJCC Manual and multiple learning resources…

The surgical approach in the management of patients with thoracic malignancies continues to evolve and improve. While conventional open surgical approaches (including standard posterolateral thoracotomy, muscle-sparing thoracotomy, trans-sternal thoracotomy, and median sternotomy) remain viable options for some patients, minimally invasive procedures are being used for an increasing number of patients with lung cancer, esophagus cancer, and thymic malignancy, to minimize operative morbidity without sacrificing oncologic efficacy.

The following sections are included:

• Introduction
• Simulation
• Treatment Planning
• Target Dose and Normal Tissue Constraints
• Quality Assurance and Patient Safety
• Image Guided Treatment Delivery
• Conclusion
• References

The following sections are included:

• Introduction to Fractionation Radiobiology
• Biophysical Interpretation of Radiation Actions
• Altered Fractionation Strategies
• Dose Response Relationships
• Tissue Organization
• Heterogeneous Dose Distribution
• Precision-Oriented Radiation Therapy
• Special Considerations for Thoracic Irradiation
• References

The following sections are included:

• Introduction
• Pathophysiology of Normal Tissue Injury
• Consequences of Concurrent Chemotherapy
• Mitigators of Normal Tissue Toxicity
• Stereotactic Radiotherapy (SBRT/SABR)
• Managing Toxicities
• References

The following sections are included:

• Introduction
• Driver Mutations in Lung Cancer
• Targeted Therapies
• Immunotherapy
• Response Assessment — Traditional Outcomes and Advancing Technologies
• Prevention
• References

In this section, the mechanisms of cytotoxic agents commonly used in thoracic oncology, together with their toxicity profile and indications, will be briefly reviewed.

Cancer is a complex heterogeneous group of diseases that manifests itself by what are now considered “hallmarks of cancer,” which include activating invasion and metastasis, inducing angiogenesis, enabling replicative immortality, resisting cell death, reprogramming energy metabolism, evading immune destruction, evading growth suppressors, and sustaining proliferative signaling. Lung cancers, the leading cause of all cancer deaths worldwide, display the aforementioned hallmarks of cancer. Evidence-based cytotoxic chemotherapies (platinum-doublets, docetaxel, and pemetrexed) and angiogenesis inhibitors (bevacizumab) for advanced non-small cell lung cancer (NSCLC) have been approved against some of these hallmarks. The last decade of care in lung cancer was advanced by the development of novel compounds that disrupt the hallmark of sustained proliferative signaling, which is usually derived from genomic mutations in key genes (i.e., oncogenes) that encode for activated kinases. Protein kinases are enzymes that transfer the gamma phosphate from nucleotide triphosphates (such as adenosine triphosphate [ATP]) to amino-acid residues in a protein substrate (which can be the kinase itself) that results in changes of protein function. Kinases fall into classes characterized by their amino-acid substrate specificity (i.e., serine/threonine-specific and tyrosine-specific). Tyrosine kinases are the most well-known proliferative signals in cancers, and over a hundred kinases — clustered into families of transmembrane receptor or cytoplasmatic/nonreceptor kinases — exist. Three main genomic events lead to the direct activation of tyrosine kinases in cancer: (1) overexpression/amplification (usually due to preferential increased copy numbers of a certain oncogene), (2) mutation (usually due to point mutations or inframe insertions/deletions), and (3) rearrangement/translocation with partner genes (usually preserving the active kinase domain) of oncogenes. All of the aforementioned changes are present in NSCLC…

The following sections are included:

• Introduction
• Mechanism of Action
• Anti PD-1 and Anti PD-L1 Therapies in Advanced, Relapsed NSCLC
• Anti PD-1 as Frontline Treatment in Advanced NSCLC
• Toxicity of PD1/PDL-1 Blockade in NSCLC
• Conclusion
• References

The following sections are included:

• Effects of EGFR-TKI Inhibition on the Epidermis
• Dermatological Adverse Events Induced by EGFR-TKIs
• Summary
• Diarrhea Induced by EGFR-TKIs
• Conclusion
• References

Percutaneous image-guided ablative therapy is a minimally invasive treatment for primary or secondary malignancies of the lung. This treatment option is especially useful for patients who cannot undergo surgery due to comorbidities or limited pulmonary reserve. Because most ablative procedures can be performed under conscious sedation and in the outpatient setting, patients can recover and be discharged sooner than if they underwent surgery. Current modalities include radiofrequency ablation (RFA), microwave ablation (MWA), and cryoablation. Treatments can be effective with palliating symptoms, increasing survival, and even potentially curing thoracic malignancies.

The following sections are included:

• Introduction
• History
• Mechanism of Action
• The Double-Edged Sword of Requiring Visible Light
• FDA-Approved PDT Applications in Thoracic Oncology
• Investigational Applications of PDT in Thoracic Oncology
• Conclusion and Future Challenges
• References

Nutrition is a key component of the effective management of cancer patients, both for those who can be cured and for those who are to be palliated. However, such patients face a wide array of difficulties that will challenge their ability to maintain their nutritional status. This section on nutrition in thoracic surgery patients deals with an evidence-based approach in general cancer patients, since specific data on thoracic cancer patients are not available.

The following sections are included:

• Practice Guidelines
• Data from Randomized Controlled Trials (RCTs)
• Mechanisms of Therapeutic and Palliative Action
• Clinical Reasoning
• Diagnostic and Therapeutic Strategies
• Study Quality
• Summary
• References

The following sections are included:

• The Impact of Pain on Lung Cancer Survival and Quality of Life
• Understanding the Multifactorial Nature of Pain
• Surgical and Radiologic Interventions
• Pharmacologic Interventions
• Acupuncture
• Manual Therapies
• Summary
• References

Acupuncture is recommended in the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines for lung cancer patients experiencing nausea, vomiting, pain, and peripheral neuropathy. Numerous mechanisms — both systemic and locoregional — contribute to the clinical benefit of acupuncture.

Many patients diagnosed with thoracic malignancies will have or will progress to advanced incurable disease and will ultimately die from their disease. Despite this, research has shown that patients are often not aware of their prognosis and that discussions about end of life are delayed until late in the disease trajectory. Lack of discussion and advance care planning is associated with more aggressive treatments and worse quality of life at the end of life. The recent Institute of Medicine (IOM) report on cancer care emphasized the importance of advance care planning and ensuring that end-of-life care plans are patient-centered. The emergence of Palliative Care and Hospice Medicine (first specialty boards administered in 2008) supports teams in addressing the need to provide higher quality care to patients with serious illness. By 2010, the majority of U.S. cancer centers had an inpatient palliative care team…

The following section is included:

• Index