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SQUAMOS CELL LUNG CANCER (SCLC), These side effects negatively impact…

- - - - Tumor Suppressor Genes Inactivation
        
        TP53 ( controls cell cycle arrest & apoptosis)
        
        This gene exhibits somatic mutations in most SCLC
        
        CDKN2A (regulates cell division)
      - Oncogene Amplifications
        
        SOX2 (drives tumor growth & proliferation)
        
        The hallmark of SCLC is represented by the amplification of chromosome 3q26 & 3q28
        
        TP63 (key in squamous differentiation, and keratin feature)
        
        PIK3CA (mutation in this gene, activates the PI3K/AKT/mTOR signaling pathway that promotes cell survival & proliferation
        
        FGFR1 (Fibroblast Growth Factor Receptor 1, drives proliferation, survival & metastasis by activating the PI3K-AKT & RAS-MAPK signaling pathways
      - Signaling Pathway Dysregulation
        
        PI3K/AKT/mTOR
        
        RAS/MAPK
        
        CDKN2A/RB1
        
        NFE2L2/KEAP1/CUL3
        
        SOX2/TP63/NOTCH1
      - Paraneoplastic Syndrome (ncrease Ca secondary to lung cancer)
        
        Tumor cells secrete Parathyroid hormone-related protein (PTHrP) which increases Ca levels
        
        Anorexia, nausea, constipation & lethargy are hypercalcemia symptoms. These, are associated w/ advance disease & poor prognosis.
- - - - Initial Dx. imaging after examination showed a mass in the R lung
    - - Show the presence of cavity, filled by gas or fluid, w/in the tumor mass. Help determine best biopsy site , lymph node involvement & co-existing lung disease
    - - Confirm diagnosis & stablishing the stage
        
        PET/CT scan of the body
        
        Provides information on tumor's metabolic activity, mediastinal involvement & potential metastasis.
        
        Can be falsely +/ falsely -
        
        Therefore, you need
        
        MRI
        
        Evaluate for possible brain metastasis
  - - - Bronchoscopic endobronchial ultrasound-transbronchial needle aspiration (TBNA)
      - Endoscopic-TBNA
      - Mediastinoscopy
      - Thoracoscopy or Video-assisted thoracoscopy (VATS)
  - - - For potential surgical candidates
    - - PD-L1
      - EGFR
- - - - Surgical resection (lobectomy)
      - IB
        
        Surgical resection & adjuvant chemotherapy (tumor > 4cm)
    - - Surgery, followed by chemotherapy
    - - Chemotherapy & radiation
      - IIIB
        
        Chemotherapy, radiation & follow by maintenance immunotherapy for 1 year
    - - Combination of chemotherapy, immunotherapy, single agent immunotherapy
        
        Platinum-bases chemotherapy
        
        Immunotherapy
        
        ICIs
        
        Nivolumab, Pembrolizumab & Cemiplimab
      - Depending of the mutation status/ molecular features of tumor
        
        Targeted therapy
        
        Currently no targeted therapy has been approved for TP53 & CDKN2A gene mutation
        
        Tailored based: ALK rearrangement, ROS1 fusion, EGFR, BRAF, Her2 mutation & PDL-1 testing
        
        PD-L1 >50%:
        
        Pembrolizumab, Cemiplimab, Atezolizumab
        
        PD-L1 1%-49%
        
        Chemo w/ pembrolizumab or cemiplimab
        
        EGFR S768I
        
        Afatinib
        
        Blocks the entire ErbB family receptors: EGFR, Her2, these interferes w/ the signaling pathways that enhances cancer cell growth & replication
        
        Epidermal Growth Factor Receptor (EGFR) exon 19 deletion
        
        Osimertinib
        
        3erd. generation Tyrosine Kinase Inhibitors (TKIs), block EGFR proteins that promotes cancer growth
        
        ROS1
        
        Entrectinib
        
        Crizotinib
        
        BRAF V600E mutation
        
        Combination of Dabrafenib & Trametinib
        
        Targets the MAPK signaling pathways, crucial for cancer cell growths
        
        Combination Encorafenib & Binimetinib
        
        Her2 mutation
        
        Trastuzumab deruxtecan is approved for second-line treatment used after chemoimmunotherapy
        
        Attaches to the Her2 receptor, once it get inside cancel cells delivers chemo (deruxtecan). Deruxtecan is permeable so it gets out of the targeted cell destroying neighboring cancer cells.
        
        Anaplastic Lymphoma Kinase (ALK) rearrangement
        
        Alectinib, brigatinib, or lorlatinib
        
        Use for metastatic treatment after surgery
        
        FGFR1 & PIK3CA are being studied in clinical trials
      - Palliative care
- - - - Immunotherapy & targeted therapy are associated w/ many side effects that negatively impact the patients' quality of life & decreases adherence to treatment therapy
        
        Common side effects of EGFR Inhibitors targeted therapy
        
        Diarrhea stomatitis
        
        Mucositis cutaneos (rash, dry skin paronychia)
        
        Liver function abnormalities
        
        Immunotherapy
        
        Skin toxicity
        
        colitis
        
        Endocrine disorders
    - - Lung cancer patients undergoing treatment face psychological stress & isolation
        
        Provide psychological support
        
        Counseling
        
        Referral to support groups
        
        Encourage participation in support groups
        
        Music therapy
    - - About disease
      - Treatment options
      - Side effects management
      - Lifestyle adjustments
        
        Stop smoking
        
        Balance diet
      - Modifiable risk factors
        
        Smoking
        
        Second hand smoking
        
        Ocupational exposures
        
        Radon gas
        
        Asbestos
        
        Diesel exhaust
      - Assess patient's health literacy
        
        Essential to identify patient's learning preferences
      - Importance to keep appointments for proper diagnostics & follow ups
      - Palliative care
        
        Focus in symptom management
        
        Psychological & spiritual support
        
        Improve quality of life, ensuring comfort & function
  - - - Provide emotional support & assistance
    - - Encourage family & friends to participate in patient's care