Clinical Flashcards
(88 cards)
1
Q
What are the three settings of chemo treatment?
A
- Adjuvant (following surgery/radiotherapy)
- Metastatic (palliative, symptomatic control)
- Neoadjuvant (shrink tumors before surgery/radiotherapy)
2
Q
What are the lymph nodes adjacent to the breast?
A
- Auxillary lymph nodes 1, 2, 3
- Supraclavicular
- Internal mammary lymph nodes
3
Q
How are breast lumps assessed?
A
- History and exam (painless)
- Mammography
- Ultrasound
- MRI
- Distant staging (bone scan, CT chest/abdo/pelvis, PET/CT)
4
Q
What is the staging system for breast cancer?
A
T1-4 (based on tumor size)
N0-3 (based on lymph nodes affected)
Mx-2 (metastatic spread)
5
Q
Pathology reports
A
- Tumor type (IDL/ILC/papillary/tubular)
- Associated (DCIS/LCIS)
- Size
- Grade 1-3
- Margins
- Lymphovascular invasion
- Nodes
- ER/PR/HER2 receptor status
6
Q
What is the most common pathological type of BC?
A
Invasive ductal carcinoma
7
Q
What is important about invasive lobular carcinoma?
A
- More likely bilateral/multifocal
- Less likely to present with defined lump
- More likely unsual spread
- Often low grade + elderly population
- Similar long term outcomes
8
Q
Cell surface receptors
A
- In both normal and cancerous cells, cellular receptors are responsible for translating signals from outside to inside cell
- Signals have numerous effects (growth, proliferation)
- Receptor activation + cell signalling tightly regulated, when poorly regulated, growth and spread of cancer
9
Q
3 cell surface receptors in BC
A
- Oestrogen receptor (ER)
- Progesteron receptor (PR)
- HER2 receptor
10
Q
What is endocrine therapy
A
- ER+ve tumors suseptible to endocrine therapy (tamoxifen, aromatase inhibitors)
- Fewer side effects? but more convenient
- Lack of cross-resistance, some merit in changing hormone therapy on progression
11
Q
Benefit of adjuvant chemo in BC
A
Absolute survival benefit of around 1-15% based on patient/tumor characteristics
12
Q
Genomic sequencing
A
- Multiple genes examined (BRCA1/2 etc)
- Mulitple mutations examined (BRCA, HER2)
- Risk of development and risk of recurrance score
- NICE-approved for node -ve ER +ve tumors to aid decision making for adjuvant chemo
13
Q
Adjuvant abemaciclib
A
- Cyclin-Dependent Kinase 4 and 6 inhibitor
- Impact on practice is major
- GI toxicity more ANC less NACT
- Sfx: diarrhoea, nausea, VTE
14
Q
Anti HER2 directed therapy
A
- Trastuzumab, mAb, ADCC (3 weekly infusions until progression, well tolerated)
- Pertuzumab (HER2 dimerisation inhibitor), blocks dimerisation
- Trastuzumab emtansine (TDM1), ADC,
15
Q
NACT with pembrolizumab
A
An immune checkpoint inhibitor, an IgG4 Ab, targets programmed death 1 (PD-1) on target T cells so they can’t turn off
- Affect on clinical service - major
- Chemosuite - longer infusion time and more treatments needed
- Clinic time doubles
- Complex toxicity management
16
Q
Chemo in metastatic BC
A
- Incurable but trying to manage symptoms
- Significant gains in progression-free survival and overall survival
- Many patients will sequence through 5/6 lines of chemo over many years
- Similar drugs to adujant settings (chemo, endocrine, anti-HER2)
- Some new agents (cdk4/6 inhibitors, mTOR inhibitors)
17
Q
How is PC diagnosed
A
- PSA in bloods
- Symptoms (frequency, nocturia, poor stream)
- Digital rectal exam
- MRI
- Transrectal biopsy
18
Q
PC pathology
A
- PSA level
- No biopsy cores involved
- % tissue involved
- Extracapular extention/seminal vesicle involvement
- Lymph node spread
19
Q
Radical treatment options for PC
A
Surgery
- Open
- Laparoscopic
- Robot
radiotherapy
- External beam therapy (conformal, IMRT, IGRT)
- LDR/HDR brachytherapy
- Active surveillance/watchful waiting
20
Q
Radical radiotherapy
A
- External beam photon therapy
- Linear accelerator
- Targeted, 20 doses over 4 weeks
- Sfx - bowel, bladder, fatigue
21
Q
Metastatic prostate cancer
A
- Commonly spread to bones
- Back bone of treatment is testosterone suppression + blockade (LHRHa, anti-androgens, endocrine therapies)
- Chemo (docetaxel, cabazitaxel)
- Radium 223
22
Q
PC in the future
A
- Increased role of IPs
- Better horizon planning of impact of new drugs on service
- Reorganisation of outpatient clinic slots
- Work with RCR/RCP on training
- Sensible treatment use (elderly + CDKi, genomic testing)
23
Q
Aetiology of lung cancer
A
- Smoking causes 80-90% of cases
- Risk relates to extent of smoking
- Stop smoking and risk reduces
- Main benefit when stopped by 30
- Other risk factors (enviroment - asbestos, passive smoke, fibrotic lung disease, family history)
24
Q
Clinical features of lung cancer
A
- Persistant or worsening cough
- Breathlessness
- Repeated chest infections
- Chest/shoulder pain
- Loss of appetite or unexplained weight loss
- Coughing up blood
- Unexplained fatigue
- Hoarseness
- Finger clubbing
- Blood clots
25
Management pathways of lung cancer
- 2ww (GP suspected, patient seen within 2 weeks for CT)
- InV (obtain biopsy/tissue diagnosis, imaging to determine extent)
- MDT (all patients discussed, review histology and imaging, management plan)
- 62 day (treatment given within 62 days from GP referral, national optimal lung cancer patheays aim to reduce to 42)
26
Diagnostic histology of lung cancer
- Bronchoscopy
- CT guided lung biopsy
- Endobrachial ultrasound - sample central lymph nodea
- US guided biopsy of neck nodes
- Surgical biopsy if otherwise inaccessible
27
Late presentation of LC
- 1/3 of cases present as emergencies
- majority presenting with advanced disease
28
Two main subtypes of lung cancer
Small cell lung cancer (SCLC) (10-15%)
- Usually caused by smoking
- Aggressive often metastatic presentation
- Treated with chemo +/- radiotherapy
- High responce but high relapse
Non-small cell lung cancer (NSCLC) (85-90%)
- Adenocarcinoma, squamous cell carcinoma, large cell carcinoma
- Molecular profile important (EGFR, ALK, ROS-1)
29
Treating SCLC
Surgery has limited role
Limited stage
- Optimal treatemtn is 4 cycles of chemo and radio
- Median survival ~2 years (5 years - 33%)
Extensive stage
- Without treatment prognosis ~ 4 months
- Chemo (carboplatin+etoposide) ~ 10 months
- Chemo-immunotheraoy + atezolizumab ~ 12 months
- 40% risk of brain metastasis
30
Treating NSCLC
Options
- Surgery
- Radiotherapy
- Systemic anticancer therapy
- Supportive care
Surgery
- Operability (tumor factors: invasiveness, size, patient factors: lung function, co-morbidities)
- Technique (laparoscopic, open)
31
Peri-operative treatment of LC
Neo-adjuvant
- Can make patients weaker if complications
- Can make patient fitter to survive surgery
Adjuvant
- Fewer patients fit enough to receive SACT as recovering
- Delay in treating microscopic seedlings
32
Adjuvant chemo in LC
- Indication (tumor >4cm, and or node involvement)
- 4-5% improvement in overall survival in 4-5 years
- 4 cycles of chemo (cisplatin + vinorelbine)
- Start with 12 weeks of surgery
33
Other options for adjuvant chemo in LC
Neoadjuvant chemo + nivolumab for 3 cycles
- Event free survival 32 vs 31 months vs chemo alone
- Complete pathological response, 24% vs 4%
- More patients had surgery
Adjuvant immunotherapy with atezolizumab
- High PD-L1 group
- 57% less likely to relapse
Adjuvant targeted therapy (osimertinib EGFR mutation)
34
Radiotherapy for lung cancer
- Stereotactic ablative therapy body radio therapy
- Conventional
- Chemo + radio
- Adjuvant immunotherapy
35
Stereotactic ablative body radiotherapy
- Very high dose radiotherapy in few fractions
- Indications: peripheral lung cancer without nodal involvement, patient unfit for surgery
- Outcomes: very good local control (>85%), minimal toxicity
36
Conventional radiotherapy
- High dose over many fractions (55Gy in 20 fractions over 4 weeks)
- Indications: inoperable non-metastatic disease, invasive or extensive nodal involvement
- Treatment limiting side effects: volume of treated lung, baseline lung function + deviation of fibrosis
37
SACT
Systemic anti cancer therapy
- Cytotoxic chemo
- Targeted agents (TKIs)
- Immunotherapy
- Antibody-drug conjugates (ADCs)
Indications
- Neo-adjuvant
- Adjuvant post-surgery chemo (cisplatin/vinorelbine)
- Palliative
38
First-line for SCLC
carboplatin + etoposide
39
First-line for squamous NSCLC
carboplatin + gemcitabine/vinorelbine
40
First-line for non-squamous NSCLC
carboplatin + pemetrexed
41
Tyrosine Kinase Inhibitors
- Targeted therapy
- Next gen drugs more selective > less off target effects/toxicities
- Expect high response rate + long progression free survival
- Resistance mechanisms
42
EGFR mutations
- ~10% of population in UK pop, ~40% in SE Asia
1st gen
- gefitinib 250mg OD
- erlotinib 150mg OD
2nd gen
- afatinib 40mg OD
sfx
- diarrhoea
- acne-like rash
- stomatitis
- paranychia
- hepatitis
43
Oral ALK inhibitors
1st line
- crizotinib, ceritinib/brigatnib
2nd line
- ceritinib is tried crizotinib first
44
Side fx of oral ALK inhibitors
- Visual disturbance
- N,V+D
- Oedema
- Rash
- QT prolongation
- Bradycardia
- Interstitial lung disease
45
Outcomes of oral ALK inhibitors
Median survival >5 years
Interpretation of trials is difficult
46
Immunotherapy
- PD-1 inhibitors: pembrolizumab + nivolumab
- PD-L1 inhibitors: atezolizumab + durualumab
- in lung cancer used as monotherapy or chemo + immuno-oncology
PDL-1
- IV over 30-60mins
- every 3-6 weeks
- since 2023, SC form available
PDL-1 as a biomarker
- tumor proportion score
- some correlation with effectiveness
- grouped as < 1%, 1-49%, >50%
47
Why Immuno-Oncology?
- quick 7 min SC, 30-60 min IV
- different toxicities than cytotoxic chemo
- no N+V, hair loss anaemia, but autoimmune sfx (managed with steroids)
- minority have prolonged response
48
Supportive measures of LC
- many unfit for SACT
- radio for symptom relief (cough, bone pain, bleeds)
- stereotactic radiosurgery for brain mets
49
Facts and figures of radiotherapy
- Second most valuable cure after surgery
- 40% cured by radiotherapy
- Treatment intents (inoperable disease, organ preservation)
- Effective palliation
50
Internal radiotherapy
Brachytherapy
- Solid radioactive source placed inside body cavity
- Prostate seeds, cervical, rectal
Radionuclide - oral or IV
- Radioactive after
- Strontium (prostate bone metastasis)
- Radioiodine for thyroid
51
External radiotherapy
- Usually given over several fractions over days/weeks
- Commonly delivered with linear accelerator
- Generation of photons
- Point in direction of tumor
- Hit target, exit in straight line
- Free radical formation, dsDNA damage
- Failed cell division - apoptosis
52
Principles of radiotherapy
- Tumoricidal dose of radiation to tumor relative sparing of surrounding tissues
- Gray (Gy) unit of dose absorbed
- Normal tissue tolerance limits dose
- Fractionation (small dose daily allows recovery of normal tissues, large dose delivered small target)
- DNA damage causes cell death during replication
53
Radiosensitiser
- improves radiobenefits when combined
Fluropyrimidines - dysregulation of s-phase of cell-cycle (rectal cancer)
Platinums - inhibit DNA repair (head, neck, cervical, lung)
54
Tumor hypoxia
- Hypoxia can cause resistance to radiotherapy
- As tumors grow, they outstrip their blood supply leading to hypoxia
Bladder carbogen + nicotinamide (BCON
- Carbogen 98%, oxygen 2% carbodioxide
- Nicotinamide orally
- Alternative to chemo-radiation in treatment of bladder cancer if chemo if CI
55
Planning and treatment summary for radiotherapy
- Majority of pt have CT planning scan
- Pt factors (ability to lie flat, remain still, stay safe unattended)
- Treat on consecutive days (10-20 mins)
- Modern planning techniques reduce dose to normal tissues
- Image guidance improves accuracy + allows smaller treatment margins
56
Radiotherapy toxicity
Localised
- only within in irradiated field
- dose-dependent + predictable
Generalised
- fatigue
- anorexia
57
Acute toxicity
- Damage of rapidly cycling cells (skin, mucus membranes, gut, bone marrow)
- Onset within 10-14 days
- Heals 2-4 weeks post RT
58
Late reactions to radiotherapy
- Dose limiting
- Predictable but not inevitable
- Aim for incidence < 5%
- Onset from 6/12 post RT
59
Supportive measures post RT
Oral mucosites - analgesics
Skin - topical opioids
Oesophageal - analgesics, diet, antacids
Bowel - laxatives
60
Principles of sugery in cancer
- Removed cancer completely
- Lymph nodes draining cancer have to be removed for staging and regional control
- Lymph nodes running alongside the artieries supplying the bowel, therefore you remove more bowel to take arteries out
61
Role of surgery in cancer
- Control of local disease
- Offer cure + extended life
- Palliate symptoms - stops bleeding, bypass obstructions
- Psychological benefits
- Facilitate chemo (reduce maligant cells + resistant clones)
62
Colorectal cancer
- Colorectal carcinoma is occurance of malignant lesions in mucosa of colon + rectum
- All are adencarcinomas (anal cancers different)
63
Bowel wall layers
- Mucosa - epithelium, lamina propria
- Sub mucosa - rich in lymphatic + blood vessels
- Muscular propria (circular + longitudinal muscle)
- Serosa
Cancers tend to grow through the layers, basis of dukes staging
64
Epidemiology of bowel cancers
- Fourth commonest cancer in UK, second commonest cancer death
- 1 in 14 men, 1 in 19 women
- Median age 60
- Higher in western areas (diet?)
65
Symptoms
- Dependent on location
- Rectal bleeding, habit changes, weight loss, iron deficient anaemia, bowel obstruction
66
Prognosis is dependent on staging
- stage 1 - 95% 5 year survival
- stage 2 - 84%
- stage 3 - 62%
- stage 4 - 7%
67
Aeitology/pathology
- Polyps
- Diet is simple, interplay with genes
- Family history - 1st degree relatives key
- IBD
- Genetic syndrome (HNPCC etc) - 75% sporadic
- Previous cancer/radiation
- Obesity/smoking/alcohol
68
Mostly adenomas
- Benign epithelial tumor of cells derived from glandular epithelium
- All dysplastic with disregulated proliferation
- Fail to fullt differentiate + all premalignant
69
Adenoma > carcinoma sequence
Normal mucosa
- (ADC activation + COX2 upregulation)
Early adenoma
- (K-Ras activation)
Intermediate adenoma
- (SMA D4 inactivation)
Late adenoma
- (p53 activation)
Metastasis
70
Macroscopic classification of bowel cancer
- Annular
- Polypoidal
- Ulcerated
71
Degree of differentiation
- Grade I - well differentiated (15%)
- Grade II - moderately differentiated (70%)
- Grade III - poorly differentiated
72
What are the modes of spread?
- Direct > invades other structures, bladder, abdo
- Lymphatic > critica;, run with blood vessels and critical in surgery
- Haematogenous > portal vein to liver, 25% of patients present with mets
- Transcoelomic > spread throughout peritoneal cavity, classically ovaries
- Implantation > suture line, wound, laparoscopic ports
73
Dukes staging
A - confined to bowel
B - through bowel wall
C - lymph node involvement
D - distant metastases
74
Genetic syndromes associated with bowel cancer
- eg HNPCC + FAP
- Important inherited bowel cancer syndromes
- Associated with other cancers too
- Screening of pt and family
75
HNPCC
Hereditary non polyposis colon cancer
- aka lynch syndrome
- 5% new cases a year
- Germline mutation in mismatch repair gene
- Average age of diagnosis - 45
- Usually develops on the right
- Synchronous + metachronous
- Biologically aggressive rapid transformation from benign to malignant
- Associated with endometrial, ovarian, gastric cancers (not as aggressive)
76
FAP
Familial adenmatous polyposis
- 1% of colorectal cancers
- APC mutation on 5q-beta-catenin + Wnt pathways
- 100% risk of CRC by 20-30s
- Autosomal dominant inheritance
- Multiple extra-intestinal manifestations
- Originally defined by presence of >100 colorectal adenocarcinoma
77
4 general symptoms of colorectal cancers
- Anorexia
- Weight loss
- Anaemia
- Fatigue
78
4 local symptoms of right sided colorectal cancers
- Abdominal mass
- Iron deficient anaemia
- Samll bowel obstruction
- Perforation
but can be symptomless
79
5 local symptoms of left sided colorectal cancers
- Rectal bleeding
- Bowel obstruction
- Fistula
- Habit changes
- Mucus discharge
80
Rectal tumors
- Rectal bleeding in 60% of patients
- CIBH including mucus PRI
- Tenesmus (incomplete evacuation)
- Rarely fistula
81
Signs of colorectal cancer
- Conjunctival pallor from anaemia
- Cachexia
- Abdominal mass
- Palpable rectal mass
- Palpable liver/jaundiced sclera
- Lymphodenopathy
82
Distant disease
- Liver: jaundice, RUQ pain, ascitie
- Lung: incidentally found on scan, SOB
- Other: lymphodenopathy, bone pain
83
Primary investigation
- Barium enemas (outdated)
- Endoscopy: flexible sigmoidoscopy + colonoscopy
- CT colonoscopy - good sensitivity/specificity
84
Loco-regional staging
- CT C/A/P - looks for mets, occasionally in elderly frail, unfit patients to rule out large obvious lesion
- MRI for rectal cancer - good for CRM + 'N' stage
- TRUS for eary rectal - assess suitablility for local excision
85
Endoscopy
- Sigmoidoscopy + colonscopy, same scope different end points
- Flexible fibre optic tubes
- Bowel prep +/- conscious sedation
- 90% caecak intubations
- 1:1000 perforations
- Can biopsy, tattoo and treat
86
CTC/CT pneumocolon
- Less invasive
- Almost 100% caecal imaging
- High sensitivity for polyps + cancer
- Can assess other abdomincal structures
87
CEA blood test
- Carcinoembryonic antigen
- Good at baseline as if tumor is a CEA secreting lesion it can be used for surveillance
88
Risks of surgery
- bleeding
- infection
- anastomotic leak
- injury to other structures
- stoma
- MI
- DVT/PE
- death
