Oncology Teaching Clinic - 3 Flashcards
What are the general and specific risk factors for colorectal cancer (CRC)?
- Dietary
- Alcohol
- Obesity
- Cigarette smoking
- Presence of coronary artery disease
Specific genetic disorders
◦ Familial adenomatous polyposis (FAP)
◦ germline mutations in the adenomatosis polyposis coli (APC) gene which is located on chromosome 5
◦ Hereditary non-polyposis colorectal cancer (HNPCC)
◦ Lynch syndrome, autosomal dominant
◦ Personal or family history of CRC or adenomatous polyps
What are the common symptoms of CRC?
◦ Change of bowel habits
◦ PR bleed
◦ Tenesmus
◦ Pain from metastasis
◦ Weight loss
◦ Anorexia
◦ Anaemic symptoms
Bilobal heterogenous non contrast enhancing
w ring enhancement with central necrosis
No ascites
What surgery for colon/ rectum?
Colon: colectomy
Rectum: abdominoperineal resection
Low anterior resection
What is the neoadjuvant therapy for CRC and what stage of cancer?
Locoregionally advanced rectal cancer (T3-4, N+, M0)
Neoadjuvant chemoirradiation
Chemotherapy: 5FU or capecitabine
Radiotherapy: 25-28 daily fractions
Pros:
Pros:
* Tumor downstage
* Facilitate complete resection
* Sphincter preservation
* In-vivo testing of chemosensitivity
* Early treatment of micrometastasis
Cons
* Delay definitive surgery
* Overtreatment
* Additional toxicities
What is the adjuvant therapy for CRC?
When is it’s recommended usage?
Recommended for all stage III (ie N+ve) and high-risk stage II (ie T3,4N-ve) disease
◦ IO, perforation, T4, PD, LVI/ PNI, LND <12, margin+
Common regimen
◦ FOLFOX4
◦ 5-FU, leucovorin, oxaliplatin
◦ CAPOX (XELOX)
◦ Capecitabine, oxaliplatin
◦ Capecitabine alone for high-risk stage II disease or old patients
What is the role of VEGF in CRC?
-Tumours >2mm in diameter require an independent blood supply to survive and grow
-Tumours continually require VEGF to recruit new vasculature
-VEGF continues to be expressed throughout tumour progression, even as secondary pathways emerge
What are the side effects of VEGF as the target in CRC?
Common side effects: Hypertension, proteinuria
Uncommon but severe: Bleeding, thromboembolic events, bowel perforation, wound healing problem
Bevacizumab: humanized IgG1mAb that blocks VEGF-A
Aflibercept: Fusion protein that blocks VEGF-A isoforms, VEGF-B, and placental
growth factor (PlGF)
Ramucirumab: human IgG1 mAb targets VEGFR-2 Regorafenib: multikinase inhibitor
What mutation is predictive of response to cetuximab therapy in colorectal cancer?
KRAS mutation
Mutated KRAS causes increased signaling despite inhibition of upstream EGFR dimeraization
What are some toxicities of anti-EGFR monoclonal antibodies?
Acneiform rash
Diarrhoea
Electrolyte disturbance
Infusion reaction
Paronychia
Conjunctivitis
Increased magnesium
What is the mechanism of immunotherapy in mCRC?
By blocking PD-1 receptors from binding to immune dampening PD-1 and PD- 2 ligands expressed on antigen presenting tumour cells, anti- PD1 mAb reactivates tumour- specific cytotoxic T- lymphocytes in the tumour microenvironment and restimulates anti-tumour immunity.
Pembrolizumab in MMR deficicent patient
What is the distribution of lung cancer?
What is most common histological type of lung cancer?
What key associated factors?
Adenocarcinoma
Non smoking history
EGFR and ALK (EML4-ALK) mutation
What are the symptoms of lung cancer?
Local symptoms
◦ Cough
◦ Sputum (color and any presence of haemoptysis) ◦ Dyspnoea
◦ Chest pain (pleuritic)
◦ Reduced exercise tolerance
◦ Neck and facial swelling (pemberton sign: IVC obstruction)
Regional symptoms
◦ Cough
◦ Sputum (color and any presence of haemoptysis)
◦ Neck and facial swelling (why?)
◦ Neck or supraclavicular fossa mass/swelling (why?)
What are paraneoplastic manifestations of lung cancer?
◦ Symptoms of Cushing syndrome
◦ Symptoms of SIADH
◦ Symptoms of Lambert-Eaton syndrome
◦ Symptoms of hypertrophic osteoarthopathy
Lung Ca, reasons for dyspnea?
Mass compressing on trachea, superior vena cava
Collapsed lung
Pneumonia in distal region (from obstruction)
Aspiration pneumonia
Pleural effusion
Lung CA
What needs to be reported?
contrast CT
Bilateral multiple hyperdense lesions
No ICH (intracerebral hemorrhage =important)
No MLS (midline shift)
Hydrocephalus, herniation, head injury
What is treatment for stage 2 lung CA?
Surgery followed by adjuvant chemotherapy (cisplatin-based doublets)
Adjuvant RT is required for incomplete resection or resection with positive margins: stereotactic body radiation therapy with active breathin control technique that employs gating technique (as tumor moves with breathing)
What is treatment for stage 2 lung CA?
Surgery followed by adjuvant chemotherapy (cisplatin-based doublets)
Adjuvant RT is required for incomplete resection or resection with positive margins: stereotactic body radiation therapy with active breathin control technique that employs gating technique (as tumor moves with breathing)
What is treatment for stage 3A lung CA?
Adjuvant chemotherapy and radiation therapy after surgery
For unresectable stage IIIA disease, concurrent chemoradiation (platinum-based) +/- induction chemotherapy is the standard of choice
Common radiotherapy regimen
◦ 63Gy/35fr/7 weeks
◦ 60-66Gy/30-33fr/6-6.5 weeks
What is treatment for stage 3B lung Ca?
Concurrent chemoRT or sequential chemoRT
Targeted therapy for targetable mutation-driven tumours (e.g. EGFR, ALK, ROS- 1 etc)
Palliative chemotherapy or radiotherapy Best supportive care
What is treatment/management of stage 4 lung CA?
Chemotherapy
Targeted therapy
Palliative radiotherapy
◦ For dyspnoea, chest pain, haemoptysis ◦ For distant metastasis e.g. bone, brain
Best supportive treatment Palliative and hospice care
What is chemotherapy related general side effects?
Nausea/vomiting
Diarrhoea/constipation
Alopecia
Immunosuppression
Subfertility
What are the specific side effects of cisplatin, paclitaxel, docetaxel, gemcitabine, vinorelbine, pemetrexed?
Cisplatin – peripheral neuropathy, nephropathy, ototoxicity Paclitaxel – hypersensitivity, peripheral neuropathy Docetaxel – hypersensitivity, neutropenia
Gemcitabine – hypersensitivity, flu-like symptom
Vinorelbine – peripheral neuropathy, phlebitis
Pemetrexed - hypersensitivity
What is the incidence of EGFR mutation in what cell type lung cancer?
What EGFR mutations?
50% asian patients with adenocarcinoma have EGFR mutation
Most common EGFR mutation
◦ Exon 19 deletion
◦ Exon 21 L858R point mutation
◦ Rarer mutations include exon 18 (G719A, G719X, S768I), double mutations
What is the most common drug resistance mutation after 1st and 2nd generation EGFR TKI?
Exon 20 T790M mutation develops in about 50% of patients as drug resistant mutation after failure to 1st/2nd generation TKI
Other resistant mechanisms
◦ MET amplification
◦ HER2 amplification
◦ Mesenchymal transformation
◦ Small cell carcinoma
What is the triple assessment of breast cancer?
Clinical exam
Imaging
Needle biopsy
What imaging used for breast cancer?
Mammogram and Ultrasound of bilateral breast
◦ To define the extent of tumor
◦ To detect the presence of multifocal tumors
MRI of bilateral breast
◦ Helpful in scarred breast and breast with implants
◦ Useful for identifying primary cancer in axillary nodal adenocarcinoma and occult (or unidentified) primary cancer
◦ Helpful for breast cancer evaluation pre and post preoperative systemic therapy to define extent of disease, response to treatment, feasibility for breast conserving therapy
◦ High false positive rate (~50%)
Bone scan, CT scan or FDG PET/CT scan
◦ Routine staging bone scan, CT scan or FDG PET/CT scan is not indicated
◦ Clinical stage I-IIB: consider only if there is suspicious symptom or abnormal blood tests (e.g. raised ALP)
◦ FDG PET/CT is most helpful in situations where standard staging studies are equivocal or suspicious, especially in the setting of locally advanced (stage III or above) or metastatic stage
What biopsies done for breast cancer?
Core-needle biopsy
◦ Provide accurate pathological diagnosis to guide management
Excisional biopsy
◦ Reserved for lesions in which the diagnosis remains equivocal despite imaging and core biopsy assessment
Fine needle aspiration
◦ For axillary lymph node staging
What are the histological subtypes of breast cancer?
Histological subtypes
◦ Invasive ductal carcinoma (IDC)
◦ Invasive lobular carcinoma (ILC)
◦ Other less common histologies (Medullary carcinoma, mucinous carcinoma, tubular carcinoma, papillary carcinoma, metaplastic breast cancer (MBC), phyllodes tumors)
◦ Lymphoma
◦ Metastatic tumors
What are histological features and biomarkers for breast cancer?
Histological features
◦ Size
◦ Status of surgical margin
◦ Grade
◦ Proliferation
◦ Vascular invasion
◦ Quantity of intraductal component
Biomarkers
◦ Estrogen and progesterone receptors (ER/PR) status
◦ HER-2 status: by immunohistochemistry (IHC) or fluorescence in-situ hybridization (FISH)
pT2N0 breast cancer management?
Patient received breast conservative therapy (BCT) plus sentinel lymph node dissection (SLND)
Systemic adjuvant therapy: Adjuvant chemotherapy – Docetaxel + cyclophosphamide for 4 cycles was given
Adjuvant whole breast radiation therapy WBRT after BCT
What is the surgical locoregional management of breast cancer?
Primary tumor
◦ Modified radical mastectomy (MRM)
◦ Breast conserving therapy (BCT) / lumpectomy
Axillary lymph node
◦ Axillary dissection (AD)
◦ Sentinal lymph node dissection (SLND)
What is the radiation therapy locoregional management of breast cancer?
Radiation therapy
◦ To reduce the chance of loco-regional recurrence by ~60%
◦ Post-mastectomy chest wall irradiation ◦ For N1, T3 or above, positive margin patients
◦ Post-lumpectomy whole breast irradiation
◦ Essential for most patients after BCT to reduce local recurrence
◦ Regional lymph nodes RT
◦ Supra-clavicular lymph node
◦ Internal mammary chain
◦ Axillary region
What is the endocrine therapy systemic management of breast cancer?
Blockade of Estrogen Receptors
◦ Selective Estrogen Receptor Modulators
◦ Tamoxifen
Pure estrogen receptor downregulator
◦ Fulvestrant
Suppression of Estrogen Synthesis
◦ Ovarian Ablation
◦ Surgical oophorectomy
◦ Irradiation of ovary
Ovarian Suppression (premenopausal women)
◦ Luteinizing hormone releasing hormone analog (LHRHa)
Aromatase Inhibitors (post-menopausal women)
◦ Anastrozole, letrozole, exemestane
What is the chemotherapy systemic management of breast cancer?
◦ Anthracycline-based: doxorubicin – cyclophosphamide (AC)
◦ Taxane-based: docetaxel – cyclophosphamide (TC)
◦ Pyrimidine analogue: fluorouracil, capecitabine, gemcitabine
◦ Platinum: carboplatin
◦ Vinca alkaloid: Vinorelbine
What is targeted therapy for breast cancer?
Indicated for HER2 overexpressed breast cancer
◦ Adjuvanttreatmentwithchemotherapyto reduce recurrence
◦ Active treatment in metastatic stage – alone, concurrent with chemotherapy or hormonal therapy
Anti-HER2 therapies
◦ Trastuzumab
◦ Pertuzumab
◦ Trastuzumabemtansine (TDM-1)
◦ Lapatinib
What are noval agents for systemic management of breast cancer?
- Cyclin – dependent kinase 4/6 inhibitor: indicated to be used in conjunction with hormonal therapy in ER +ve / HER2 –ve metastatic breast cancer
- Inhibitor Mammalian target of rapamycin (mTOR) signal transduction pathway: indicated to be used in conjunction with hormonal therapy in ER +ve / HER2 – ve metastatic breast cancer
- Poly (ADP-ribose) polymerase (PARP) inhibitors: indicated in BRCA mutation- associated metastatic breast cancer
- Immune checkpoint inhibitor in triple-negative breast cancer
What is the general approach of breast cancer?
What is standard treatment of stage 0 breast cancer?
Ductal carcinoma in situ (DCIS)
Local treatment only
Standard treatment
1. Modified radical mastectomy (MRM)
2. Breast conserving therapy (BCT)/lumpectomy, followed by whole breast radiation therapy
What is management of stage 1 breast cancer?
What is management of stage 2-3A breast cancer?
What is management of stage 3B-3C (T3-4, N2-3) breast cancer?
Systemic management of stage 4 breast cancer
What are the toxicities of chemotherapy and management of late stage diseases?
Cardiac toxicity due to anthracycline based chemo and/or RT (not reversible heart damage)
Bone health, esp those on aromatase inhibitor
Lymphedema
Anxiety, depression and fear of recurrence
Early menopause / fertility
Sexuality
Sleep disorder
Healthy lifestyle and physical exercise
What investigations to order with left middle ear effusion, bilaterally enlarged cervical LNs?
Blood for Complete blood count, LRFT, creatinine clearance, LDH Hep B serology
EBV serology incl. Anti-EBV EA, Anti-EBV VCA
EBV DNA – a very sensitive tumour marker for NPC Nasopharyngoscopy and biopsy
Pure-tone audiography (PTA)
Dental checkup
MRI of NP and neck region +/- PET scan Dietician consultation
What is management of advanced stage NPC?
◦ Concurrent chemoradiation is the standard
◦ Cisplatin
◦ 100mg/m2 on D1, D22, D43 ◦ 40mg/m2 weekly
◦ RT still 70Gy in 35 fractions over 7 weeks, further dose escalation does not improve survival
What are the radiotherapy techniques for NPC?
2-dimensional conventional RT
3-dimensional conformal RT
IMRT
Brachytherapy (for persistent/recurrent disease) Stereotactic radiosurgery (for persistent/recurrent disease) Cyberknife (for persistent recurrent disease)
What is 2D conventional radiotherapy and long term issues?
Lateral opposing beams to both sides of head and neck regions
RT to swallowing muscles and parotid gland
What are the acute side effects of radiation therapy?
◦ Mucositis/sore throat (口腔黏膜炎)
◦ Odynophagia/dysphagia (吞咽痛楚及困難)
◦ Xerostomia (口乾)
◦ Oral candidiasis (口腔念珠菌病)
◦ Hearing impairment/tinnitus/otitis media (聽力減弱,耳鳴,中耳炎)
◦ Desquamation (脫皮)
What are the common and uncommon chronic side effects of radiotherapy?
Chronic (common) 常見長期副作用
◦ Xerostomia (口乾)
◦ Hearing impairment/tinnitus/otitis media
◦ Hyperpigmentation of skin (皮膚色素加深) ◦ Fibrosis of neck muscles (頸部肌肉纖維化)
Chronic (uncommon) 不常見長期副作用
◦ Trismus (牙關緊閉)
◦ Osteoradionecrosis of jaw (顎骨壞死)
◦ Hypopituitarism (腦下垂體功能減退)
◦ Oesophageal stricture (食管狹窄)
◦ Radiation-induced 2nd malignancy (放療引發第二種癌症)
What is chemotherapy for NPC?
Cisplatin (given if renal function is fit)
Carboplatin (Used if renal function not optimal)
5-FU
Chemosensitizing effect with RT
What is treatment of local recurrence of NPC?
Surgical resection e.g. maxillary-swing nasopharyngectomy ◦ 5-year local control rate: 65%
◦ 5-year progression-free survival: 54%
Stereotactic radiosurgery/radiotherapy
Intensity Modulated Radiation therapy
Cyberknife
+/- Concurrent chemotherapy
What is treatment for neck LN recurence?
IMRT
Radical dissection
Interstitial brachytherapy (has already undergone RT before)
What is choice of chemotherapy for NPC?
