​Kembara Xtra - Medicine - Primary Lung Malignancies

​Kembara Xtra - Medicine - Primary Lung Malignancies 
Primary lung cancers, which are predicted to have caused 154,050 cancer-related deaths in the US in 2018, account for 25.3% of all cancer-related deaths.
 Arranged into two major areas. - Non-small cell lung cancer (NSCLC) makes up more than 85% of lung malignancies and typically develops in the periphery.  Lepidic growth, a form of adenocarcinoma, has a better prognosis. Adenocarcinoma (40% of NSCLC) is the most prevalent type in the United States and affects both smokers and nonsmokers. It metastasizes earlier than squamous cell carcinoma.
Squamous cell carcinoma (SCC), sometimes referred to as epidermoid carcinoma, makes up about 25% of NSCLC and has a dose-related effect on smoking. It also grows more slowly than adenocarcinoma. Small cell lung cancer (SCLC) (16% of all lung cancers) is centrally situated, has early metastases, and is aggressive. Large cell lung cancer (10% of NSCLC) has a prognosis comparable to adenocarcinoma. Other cancers include mesothelioma and carcinoid tumor  Staging - Both NSCLC and SCLC are graded from I to IV based on the existence of metastases (M), the size of the main tumor (T), and the condition of the lymph nodes (N). - SCLC was staged further by:
Disease that is only present in the ipsilateral hemithorax.
Extensive disease: beyond ipsilateral hemithorax (stages IIIB and IV), which may involve hematogenous metastases (stage IV) or malignant pleural or pericardial effusion  The distribution of tumors was as follows: upper: 60%; lower: 30%; middle: 5%; overlapping and main stem: 5%.
 May spread locally to the chest wall, the diaphragm, the vena cava, the phrenic nerve, the esophagus, or the pericardium.  Liver, adrenal glands, bones, and brain are the organs that metastasis to lymph nodes (pulmonary, mediastinal) most frequently.

Epidemiology Incidence In the United States, there will be more than 230,000 new cases of lung cancer in 2021, along with 130,000 fatalities.
Overall, lung cancer kills more people than all other cancers combined, including breast, prostate, colorectal, and brain.
 The average diagnostic age is between 65 and 74 years old, peaking at 70 years old. Both men and women are experiencing a decline in lung cancer fatalities as a result of smoking cessation, with over half of all lung cancer deaths occurring in women.

Prevalence
Population-level mortality from NSCLC in the United States fell significantly from 2013 to 2016, while survival after diagnosis increased significantly. Mortality from SCLC decreased nearly entirely as a result of reducing incidence, with no improvement in survival.

Pathophysiology and Etiology 

Genetics NSCLC
Ras family (H-ras, K-ras, N-ras), EGFR, NTRK, ALK, etc. are oncogenes. Retinoblastoma and p53 are tumor suppressor genes.

Risk factors include smoking, exposure to secondhand smoke, radon, and occupational and environmental exposures. - Air pollution - Asbestos exposure (risk for smokers increased synergistically) - Ionizing radiation - Gases that can cause mutations (mustard gas, halogen ethers, aromatic hydrocarbons) - Metals (inorganic arsenic, nickel, and chromium)
 Breast or chest radiation therapy Tuberculosis-related lung scarring

Prevention 
Smoking prevention and cessation initiatives
 Screening, which is advised by the National Comprehensive Cancer Network (NCCN) and has been found in the National Lung Screening Trial (NLST) to lower mortality.
As of March 9, 2021, the USPSTF advises persons aged 50 to 80 who have a 20 pack-year smoking history and who currently smoke or have quit within the previous 15 years should undergo an annual screening for lung cancer using low-dose computed tomography (LDCT) (2).
 Prevention through aggressive smoking cessation counseling and therapy; a 20-30% risk reduction occurs within 5 years of quitting; screening should be stopped once a person has not smoked for 15 years or develops a health issue that significantly reduces life expectancy or the ability or willingness to undergo curative lung surgery.


Accompanying Conditions 
Hypercalcemia from ectopic parathyroid-releasing hormone (PTHrP), hypertrophic pulmonary osteoarthropathy, Lambert-Eaton syndrome (LES), Cushing syndrome, syndrome of inappropriate antidiuretic hormone (SIADH), and hypertrophic pulmonary osteoarthropathy are examples of paraneoplastic syndromes.  Hypercoagulable condition
Other effects of smoking include superior vena cava (SVC) syndrome, pleural effusion, chronic obstructive pulmonary disease (COPD), and pancoast syndrome.
DIAGNOSIS HISTORY Most people, of course, may not experience symptoms  Respiratory - Cough (new cough or modification of chronic cough)
- Constitutional - Malaise - Bone pain (metastatic disease) - Dyspnea - Hemoptysis - Pneumonitis (fever and productive cough)
Fever, anemia, weight loss, fatigue, and other manifestations
- Pleuritic, dull chest pain
- Shoulder/arm ache (tumors on the Pancoast)
Dysphagia and Plethora (facial or neck redness)
- Hoarseness (recurrent laryngeal nerve involvement)
- The Horner syndrome.
- Neurologic problems, including pericardial tamponade (pericardial invasion), headaches, syncope, paralysis, and cognitive impairment.

clinical assessment 
Head, eye, ear, nose, and throat (HEENT): Horner syndrome, dysphonia, stridor, scleral icterus, and dysphagia General: fever, chills, night sweats, and weight loss  Extremities: symptoms of hypertrophic pulmonary osteoarthropathy, deep venous thrombosis (DVT), fingernail clubbing Neck: supraclavicular/cervical lymph nodes, mass Lungs: effusion, wheezing, airway obstruction, dyspnea Abdomen/groin: hepatomegaly or lymphadenopathy Neurologic: headache, syncope, weakness, cognitive impairment

Differential Diagnosis: Granulomatous (tuberculosis, sarcoidosis), Cardiomyopathy, Congestive Heart Failure (CHF), COPD (may coexist), 

Laboratory Results 

Initial examinations (lab, imaging)
● Serum
- Comprehensive metabolic panel (CMP) - Complete blood count (CBC): For hyponatremia (SIADH), check.
- Serum calcium: Look for paraneoplastic syndrome (hypercalcemia).
- Sputum cytology, Lactate dehydrogenase (LDH),
 Chest X-ray (CXR) (Consider previous X-rays.) Nodule or bulk, particularly if it is calcified
Atelectasis, persistent infiltration, and mediastinal widening
- Pleural effusion and expansion of the hilar
 Chest CT scan (with IV contrast) - Central or peripheral nodule or bulk
- Lymphedema
 Positron emission tomography (PET) scan to assess mediastinal lymphadenopathy from metastases (replacing CT abdomen/pelvis and bone scan) - Brain MRI: Necrotic and bleeding lesions are possible.
Tests in the Future & Special Considerations
CBC, BUN, serum creatinine, and LFTs are taken before each treatment cycle.

Other/Diagnostic Procedures
Pathology review utilizing biopsy - Bronchoscopy with transbronchial biopsy (WANG needle); typically used for malignancies with a central location - CT-guided biopsy of a lung mass or a metastatic location, typically for cancers that are located in the periphery. - Endobronchial ultrasound (EBUS)-guided fine-needle aspiration - Mediastinoscopy, video-assisted thoracoscopy, and EBUS-guided fine-needle aspiration are required for staging of enlarged mediastinal lymph nodes.
Pulmonary function tests (PFTs) In patients with advanced NSCLC, screening for mutations in EGFR, BRAF, KRAS G12C, NTRK, ALK, ROS1, MET exon 14, and RET non-SCC (NSCC) or mixed squamous histology Video-assisted thoracoscopy (related pleural disease and possible mediastinal nodal dissemination  Bone marrow aspirate (small cell) with PD-L1 testing Interpretation of Tests
Smoking causes progressive pathologic alterations, including basal cell proliferation, abnormal nuclei formation, stratification, squamous cell metaplasia, carcinoma in situ, and ultimately invasive illness.


Management 

Stage I, stage II, and a few stage III NSCLC tumors can be surgically removed. For some individuals with high-risk IB, II, and IIIA NSCLC, neoadjuvant or adjuvant therapy is advised. Radiation therapy is an option for patients who have resectable illness but are not surgical candidates. Unresectable or N2, N3 illness patients receive concomitant chemotherapy and radiation therapy, followed with maintenance immunotherapy. A combination of surgical resection and either pre- or postoperative chemotherapy or chemoradiation therapy can effectively treat some individuals with T3 or N2 illness. Chemotherapy, targeted therapy, immunotherapy, radiation therapy for palliation, or the best supportive care alone may be used to treat patients with distant metastases (M1B).
SCLC - Limited stage: concurrent chemoradiation - Extensive stage: combined chemotherapy and immunotherapy - Take prophylactic cranial irradiation (PCI) into consideration in patients who achieve a full or partial response (3)[A].
 Eastern Cooperative Oncology Group (ECOG) and Karnofsky Performance Status (KPS) scales were used to evaluate quality of life.  Discussions concerning end-of-life care with the patient and family

The mainstay of treatment is medication, specifically chemotherapy, targeted treatments, and immunotherapies.
Patients with totally resected stages II and III NSCLC have a better prognosis when given adjuvant chemotherapy after surgery.
Palliative treatments include analgesics. Oxygen and morphine for dyspnea
Initial Line
Stages II and III of NSCLC: neoadjuvant versus adjuvant chemotherapy
Cisplatin-based doublets (combination with paclitaxel, etoposide, vinorelbine, docetaxel, and gemcitabine) Carboplatin as an option for patients who may have a hard time tolerating cisplatin Cisplatin plus pemetrexed (NSCC) - Unresectable stages IIA, IIIB
Concurrent chemoradiation includes the following treatments: Carboplatin plus paclitaxel plus concurrent radiation; Cisplatin plus etoposide, vinblastine, or pemetrexed (NSCC) plus concurrent radiation; Cisplatin plus pemetrexed (NSCC) plus concurrent radiation. Durvalumab consolidation following chemotherapy and radiation for stages III to stage IV
No chemotherapy plan may be suggested for everyday use.
In the absence of targetable mutations, doublets based on carboplatin or cisplatin are the norm.
Pembrolizumab, atezolizumab, or cemiplimab monotherapy for NSCLC with PD-L1 expression 50% of tumor cells Pemetrexed plus carboplatin for adenocarcinoma without EGFR, ROS, or ALK mutations regardless of PD-L1 expression Osimertinib is the first option for the majority of EGFR mutation patients. For untreated patients with BRAF V600E mutations, dabrafenib and trametinib  For untreated ALK-positive NSCLC, alextinib, lorlatinib, crizotinib, brigatinib, ceritinib, or alextinib
 For individuals with ROS1-positive non-small cell lung cancer, crizotinib, ceritinib, or entrectinib
For malignancies with the KRAS G12C mutation, sotorasib; for tumors with the NTRK fusion, larotrectinib or entrectinib.  Tepotinib, capmatinib, or crizotinib for MET exon 14 skipping mutation-positive cancers  Vandetanib, cabozantinib, pralsetinib, or selpercatinib for cancers with RET rearrangements In advanced stages of the disease, SCLC patients should get atezolizumab in addition to carboplatin or cisplatin and etoposide. Next Line
If not previously used, NSCLC patients receiving cisplatin-based doublets plus bevacizumab (NSCC) - Docetaxel +/- ramucirumab, pemetrexed (NSCC), gemcitabine, or nivolumab (squamous cell) if not previously used. If the disease worsened during or after the first-line platinum-based medication, immunotherapy might be tried.
Clinical study, topotecan, or lurbenectedin for SCLC. Alternatives include gemcitabine, docetaxel, paclitaxel, nivolumab, and temozolomide. CAV (cyclophosphamide, doxorubicin, vincristine) is another option.


Consider IV bisphosphonates or denosumab in patients with bone metastases to minimize skeletal-related events. Additionally, consider smoking cessation counseling.

Surgical Techniques 
NSCLC resection for stages I, II, and IIIA if a patient is medically able to have surgery. It has been possible to remove isolated, far-off metastases, which might increase survival.
Resection should be followed by lymph node dissection for pathologic staging. Resection involves lobectomy in 71%, wedge in 16%, and full pneumonectomy in 18%.

Patient Follow-Up Monitoring
 Depending on clinical history, postoperative visits typically occur every 3 to 6 months in the first 2 years following surgery and include a physical examination and CT scan. Follow-up is typically lifelong with CT scans, in accordance with NCCN criteria.


The 5-year survival rate for all types and stages combined is 18.6%.
NSCLC 5-year survival for localized illness is 92%, 83%, and 77% for stages IA1, IA2, and IA3, respectively; 68% and 60% for stages IB and IIA. - Regional disease: 36%, 26%, and 13% for stages IIIA, IIIB, and IIIC, respectively. - Distant metastatic disease: 10% and 1%, respectively, for stages IVA and IVB. Without therapy, the median time from diagnosis to death for SCLC is only 2 to 4 months, and the 5-year survival rate ranges from 2% (stage IV) to 31% (stage I). - Long-term disease-free survival in advanced disease is uncommon, with a median survival time of 6 to 12 months.

problems include: local cancer recurrence, metastatic disease development, postoperative problems, and radiation or chemotherapy side effects.