Lung cancer

Background info
● General info
○ Lung cancer is the most common cancer in the world in incidence and mortality
○ Leading cause of cancer deaths for both men and women
○ 1.2M new cases per year; 1M deaths per year
○ Majority diagnosed with locally advanced or metastatic disease
● Cx
○ Tobacco smoking is the single most predominant Cx
○ Workplace agents: asbestos, arsenic, chromium, nickel, radon
○ Environmental agents: passive smoking, indoor radon, air pollution
○ Genetic susceptibility to causal factors
● Pathogenesis
○ Initiation -> promotion -> conversion -> progression -> metastasis
○ Early phase: normal epithelium -> hyperplastic form
○ Intermediate phase: hyperplastic epithelium -> dysplasia
○ Late stage: potential development of carcinoma in situ that can lead to invasive carcinoma
● Ix
○ Aims: stage disease (for purpose of Tx options) and assess operability (if metastases absence)
○ CXR: normally 1st line in primary or secondary care
○ CT
■ Chest + abdo, and to inc. liver and adrenals
■ More detailed assessment of ^ (liver and adrenals are common sites of lung cancer
metastatic disease)
■ Diagram A: v large right-sided
mediastinal soft tissue mass,
associated with complete
occlusion of SVC
■ Diagram B: liver enlarged;
contains innumerable focal
solid lesions that are
consistent with metastases
○ Bronchoscopy
■ Information regarding presence and features of endobronchial lesion
■ Allows performance of washings and brushings for cytology assessment
■ Allows for obtaining of tissue biopsies for histological confirmation
○ Endobronchial ultrasound (EBUS) + mediastinoscopy
■ Provide valuable information regarding lymph node status of
patient
■ Allow sampling for cytology or histology tests
○ Pulmonary function tests
■ Provide information regarding patient’s ability to tolerate
surgical intervention or high doses of chest radiotherapy
(both can have a significant effect on the patients
subsequent lung capacity)
○ PET/CT
■ Establish operability by further excluding/confirming distant
metastatic disease
■ Provide more detailed info regarding extent of primary
tumour
■ INDISPENSIBLE - without PET/CT, lung cancer surgery
should not be performed
■ Diagram (right): lesion in left lung demonstrating avid FDG
(Fludeoxyglucose/18F) uptake consistent with SCLC
○ Bone scan and CT or MRI brain (for >/ N2 disease)
■ Complete the investigations in
patients with significant LN disease
in NSCLC and all cases of SCLC
■ Diagram A: bone scan revealing
multiple bone metastases shown as
dark spots throughout the skeleton
in the anterior and posterior views
■ Diagram B: CT scan of brain
demonstrating multiple metastatic
lesions with largest showing marked
surrounding oedema
 ● Dx
○ Cytology
■ Washings/brushings during bronchoscopy
■ Pleural/pericardial fluid aspiration
■ EBUS
■ Inadequate for specialised immuno-histochemistry tests
○ Tissue biopsy
■ Bronchoscopy
■ CT- or US-guided mediastinoscopy
■ Surgical
■ Good cores - ideal for extensive immunohistochemical
tests
● S/S
○ Main cause: primary tumour - dyspnoea, cough, pain,
haemoptysis, SVC obstruction (picture right showing distention
of superficial upper chest and development of compensatory
collaterals), pleural & pericardial effusions, laryngeal nerve
paralysis (with onset of hoarse voice)
○ Main cause: metastatic disease - bone metastases (pain, pathological
fractures, cord compression), brain metastases (w oedema,
headaches, or even seizures), liver metastases, adrenal metastases
etc.
■ Diagram right: MRI showing soft tissue mass involving C7-T2,
with collapse of vertebrae and moderate cord compression
● Mx
○ Symptom control
■ Draining of pleural effusions
● Temporary draining systems
● In-dwelling catheters
■ Pleurodesis
● Talc
● Bleomycin
● Tetracycline
■ Draining of pericardial effusions
● Pericardial window
■ Stents
● Endo-tracheal
● SVC
● Histological types
○ Non-small cell lung cancer (NSCLC) - 75-80% of lung cancers
■ Adenocarcinoma/ squamous cell carcinoma/ large cell carcinoma
■ Patients with mutations in ATP-binding site of EGFR tyrosine kinase (TK) domain respond to
TK inhibitors (TKI)
● Majority of EGFR M+ cases are adenocarcinomas
● Patients with KRAS mutations are resistant to EGFR TKIs
○ EGFR and KRAS mutations are mutually exclusive
○ Small cell lung cancer (SCLC) - 15-20%
○ Bronchio-alveolar carcinoma - ~5%
○ Rare tumours: carcinoid etc - ~1%
● Survival/prognosis
○ Survival depends on early detection and improvements in systemic therapies applied to surgery
and/or radiotherapy in early stages of disease
○ Large proportion of early disease patients experience disease recurrence
○ Only 14% of all lung cancer patients will be alive 5 years post-Dx
NSCLC 5-year survival SCLC 5-year survival

● Early stages 40-70% ● Limited disease 15-25%

● Locally advanced/metastatic disease ● Extensive disease <5%
○ Median survival 8-11/12
○ 1-year survival 30-35%
○ 2-year survival 10-15%
NSCLC
● Background
○ ~80% of all lung cancers
○ NSCLC Tx defined by the disease stage
■ Surgery is mainstay for early and localised disease
■ Systemic therapies can also benefit earlier stages and have become part of the multimodal
 approach for stages II & III
■ Regionally advanced disease usually treated with multimodality therapy
■ Advanced and metastatic disease benefit by systemic therapies, which improve survival and
quality of life
○ Early stage disease
■ Surgical resection is the only curative approach
● Wedge resection, segmentectomy, lobectomy, pneumonectomy
■ Increasing evidence that if combined with systemic therapy, can improve outcomes for
stages Ib-IIIa
○ Regionally advanced disease: includes heterogenous stage subsets of stage III disease (T3N1/
T4N?/ T?N2/3)
■ Microscopic vs macroscopic LN and low vs high volume lung disease affect prognosis
■ Chemotherapy and concurrent radiotherapy is the Tx of choice for advanced stage III
disease
■ Minimal tumour volume and/or microscopic N2 disease can potentially undergo surgery
upfront
● Still unclear role of pre-operative and post-operative chemotherapy
■ Surgical resection following chemotherapy +/- radiotherapy is controversial but considered
● Tri-modality therapy for T4N0/1 and superior sulcus tumours
○ Advanced and metastatic disease
■ Advanced disease = distant metastases; pericardial, pleural effusions or otherwise
inoperable disease
■ 40% at presentation
■ Patient Tx depends on:
● General condition or performance status (PS)
● Histological subtype
● Tx
○ 1st line treatments
■ Good performance status (PS 0-1): no symptoms OR minimal symptoms not compromising
patient’s daily activities
● Combination of ⅔ chemotherapy agents OR
● Molecular targeted agents if EGFR mutation present
■ Tx according to histological subtype
● If EGFR mutation +ve
○ Anti-EGFR TKI Gefitinib
● If EGFR mutation -ve
○ Squamous cell cancer: platinum-based + 3rd gen agent (gemcitaine,
taxanes, vinorelbine)
○ Non-squamous histology (adenocarcinoma, large cell): platinum-based
and pemetrexed
■ PS 2: symptomatic bu ambulatory >50% of day; poor prognosis; not well-defined standard
therapy
● Single agent therapy can be used especially when co-morbidities are present
■ PS >/3: symptomatic and confined to bed >50% of day OR very unwell and continuously
bedbound
● Palliative approach with symptom control
○ 2nd line treatments
■ 30-40% of patients suitable for 2nd line therapy
■ Chemotherapy: pemetrexed (non-SCC histology), docetaxel
■ Molecular-targeted therapies: anti-EGFR TKI (erlotinib)
■ Optimise symptoms and palliative care support
○ Surgery
■ Curative for early stages
■ Palliative surgery: role in selected cases for symptom control
● Solitary brain metastases, pathological fractures, palliative lung surgery
○ Radiotherapy
■ Neo-adjuvant (pre-operative)
● Tumour shrinkage
● To achieve complete surgical resection
● In combination with chemotherapy for tumours high risk for local recurrence
■ Adjuvant (post-operative)
● To prevent local recurrence in N2 disease - no improvement in OS
● When surgical margins +ve and repeat surgery is no possible
● As part of clinical trials
■ Palliative
● External beam
○ Primary tumours and metastatic disease
○ Various dosing protocols
 ○ Gamma knife
● Brachytherapy
○ Not routinely used
○ Selected cases
○ Chemotherapy
■ Neo-adjuvant
● Tumour shrinkage
● Eradication of micro-metastases
● Unresectable/marginally resectable tumours
● Stage IIIa
● T3 Pancoast tumours (2-year overall survival 50-70% vs 20%)
● Alone or combined with radiotherapy
■ Adjuvant
● Cisplatin-based Tx - 13% reduction in risk of death
● Chemotherapy + radiotherapy - no additional advantage
■ Metastatic disease
● Chemotherapy vs no Tx: improved 1-year survival by 4/12 in ~20% patients
○ Patients with good PS
● Until 1990s - single agent cisplatin
● Two agents better than one
● New combinations have improved outcomes: paclitaxel/cisplatin vs
etoposide/cisplatin
● 3-4 cycles vs 6 cycles
○ Better tolerated, lower toxicity
○ No survival benefit
● 2nd line therapy
○ Docetaxel vs supportive care
○ Docetaxel vs vinorelbine or ifosfamide
● Solitary metastasectomy
○ Not standard practice
○ Unclear benefits on survival

SCLC
● Background
○ Chemosensitive and radiosensitive, but rapid doubling time and tendency for early metastases
● Staging
○ Limited disease: encompassed within one radiotherapy field
○ Extensive disease: disease not limited within one radiotherapy field
○ At presentation only ~30% limited disease
○ Chemotherapy the backbone of Tx
Year 4 Medical Student Oncology Tutorials 2015/16
Lung cancer – Case 1

Case and questions given to the students

EGFR mutations in non-smokers, adenocarcinoma, usually women

● Tx: gefitinib…
● New gen: nefatinib… ersimertinib - more potent generation (ersimertinib often considered first in EGFR
mutation(?))
ALK mutations - rarer than EGFR
● Tx: quizotinib(?)
○ Not available in NHS
● Alextinib(?) - has two-years’ effectivity?

A 76 year old man presents with a 2 month history of cough. He has had two courses of antibiotics from his GP. In
addition he has been suffering from mild back pain

1. What are the relevant elements to elicit in the history and on examination?
● History
○ Cough
■ Fever
■ Productive?
■ Weight loss
■ Night sweats
○ Pain localisation - back pain
■ Night pain
● Examination
○ Neurological (for back pain)
■ Weakness?
○ Respiratory examination
○ Cardio examination
○ Clubbing, cyanosis, horners…
●
1. How would you proceed? What kind of investigations do you arrange? Are there any other tests you would
request from the histopathologists?
● CXR
● CT Chest and abdo
● Bone scan
● Blood counts - FBC, LFT, U&E; clotting (for determining whether to do biopsy later)
● Biopsy
○ Bronchoscopy
○ Core biopsy (radiologist)
● Cytology - though current day don’t really do this

Investigations confirm an opacity in the upper lobe of the right lung, which is invading the ribs posteriorly and
a lesion of the left adrenal gland

Biopsy confirms non-small cell lung cancer (adenocarcinoma)

EGFR mutation negative

 Bone scan shows uptake at T10

1. What are the treatment options? What is the prognosis?

● Chemotherapy
● Radiotherapy - to lung and/or primary (rib)
● Pain relief: morphine, bisphosphonates (for bone mets)

● Stage 4 (metastatic) = poor prognosis

○ Median survival ~1-1.5 years

1. Ten days after receiving his first cycle of chemotherapy he phones the ward, complaining of feeling hot and
shivery. What would you advise?
● High risk of neutropenic infection
● Get patient in for Ix - FBC etc

1. One months later he attends outpatients, complaining of a two week history of a droopy right eye and pain in the
little finger of his right hand. What else would you look for? What is the name of this syndrome? What is its
anatomical cause? What are the treatment options?
● Horner’s
1. Two months later he attends A&E with a 4 day history of weakness of his left leg. How do you proceed?
● Worried about cord compression - do MRI of full spine
Investigations confirm cord compression at level T10

1. What are the treatment options? What is his expected survival? What do you need to do?
● Decompression! Or radiotherapy?
● Considerations?
○ Clinically well?
○ What’s the prognosis?
○ Any other Tx options? Is radiotherapy an option?
○ Single site bone met?
○ How long has he been presenting for? - if something like 5 days, probably won’t get function back
● Survival: ~3/12
○ Cord compression -> need to get back on his feet. If not, paralysed -> bed sores, DVTs, PEs, chest
infection…

Year 4 Medical Student Oncology Tutorials 2015/16

Lung cancer – Case 2

A 64 yo lifelong smoker presents acutely to A&E with dyspnoea, facial, neck and arm swelling and headache. His wife
reports that the swelling is worse in the mornings and that his symptoms are made worse by leaning forward or lying
down.

1. What is the most likely diagnosis?

a. SVCO (SVC obstruction)
2. What would you include in your differential?
a. DDx: lung cancer, lymphoma, mediastinal disease (thymoma, thyroid cancers, mets from anywhere)
3. What is the most likely underlying aetiology causing this condition?
a. SCLC
i. Rapid SVCO
ii. Age range appropriate
4. What signs would you look for on clinical examination?

The patient is in A&E, the nurses are trying to lie him down on a stretcher to transfer him up to an oncology ward.

1. Would you intervene at this stage and do anything differently?

● Lying flat -> reduction of further back flow to the heart = BAD
● Presenting w stridor - stenting is recommended for SVCO

The patient is stabilized and transferred to the ward.

1. How would you proceed to investigate this patient?

A CT-guided biopsy is obtained.

1. What is the histological diagnosis? What treatment would you give this patient?
a. Chemo is mainstay then introduce radiotherapy
 b. Never do surgery - metastatic from the onset
c. Steroids?
d. Not curable

Year 4 Medical Student Oncology Tutorials 2015/16

Lung cancer – Case 3

73 yrs old male presented to GP with history of cough and haemoptysis for 6 weeks.

1. What other relevant history you would like to find out? What would be your next investigation of choice?

CXR shows 2 cm lesion in right lung

2. What would you do next?

● CT
● EBUS
● PET
● Surgery; what to know?
○ Basis of pulmonary function - total lung capacity, FEV1, smokers?, good carotids? Cardiac ok?

Histology confirms NSCLC (squamous cell carcinoma).

3. What would you do next?

Staging investigations show no other lesions elsewhere: T2N0M0 disease

4. What are the available treatment options?

● Radiotherapy: radical. (cf. stereotactic radiotherapy)
○ Smaller doses, but many days of radiotherapy
■ In total much higher dose
■ Avoids extensive damage to normal cells
■ Tolerance: normal tissue has a tolerance to radiotherapy
○ Long term side effects
■ Secondary malignancies
● Immunotherapy - pembulizumab
○ Non-targeted
○ Harnessing immune system to try and kill foreign bodies
■ Inhibiting the check point ‘dodging’ by cancer cells, enabling immune system to recognise
the foreign cells etc
○ Risk of worsening autoimmune diseases: RA, pneumonitis, colitis, hepatits...
5. What is the prognosis and 5yrs survival rate?
● Median survival for N1 = 40%
● N0 = 70%
● N2 = 15%
● Cf. stage 1 breast or bowel cancer w a 5y survival of 90-95%

Prostate cancer

Incidence
● Most common cancer in men in the UK
● Accounts for 25% of all new cases of male cancer
● Lifetime risk of developing prostate cancer 1:8

Presentation
● Screen detected - raised PSA
● Symptoms of urinary osbtruction, e.g.
○ Decreased urinary stream
○ Urgency
○ Hesitancy
○ Nocturia
○ Incomplete bladder emptying
● Symptoms of metastatic disease
○ Bone pain
○ Pathologic fractures
○ Renal failure
○ Weight loss
Investigations
● PR
● PSA
● MRI prostate
● Biopsy
● Distant staging - bone scan, CT CAP

Diagnosis
● Castration resistant prostate cancer (CRPC)
○ Three consecutive rises of PSA 2/52 apart resulting in two 50% increases over the nadir
○ Castrate serum levels of testosterone
○ Antiandrogen withdrawal for at least 4/52
○ PSA progression despite secondary hormonal manipulations
○ Progression of bone or soft tissue lesions

Staging
● TNM

● Gleason score
○ Not cytological - looks at organisation of acini,
graded 1-5
○ 1: resembles normal prostate tissue
○ 5: no recognisable glands
○ Two most widespread scores added for a final
score
■ High score = more aggressive and worse
prognosis
 ● Terminal stages of advanced prostate cancer
○ Pain
○ Skeletal events - pathological fracture,
MSCC (metastatic spinal cord
compression)
○ Bone marrow infiltration
○ Ureteric obstruction
○ Haematuria

Treatment
● Prostatectomy
○ Side effects
■ Surgical risks - infection, bleeding
etc
■ Urinary incontinence
■ Sexual dysfunction
■ Infertility
■ Lymphoedema
● Radical radiotherapy
○ External beam radiation
■ Short term
● Bladder and rectal irritative symptoms (e.g. frequency and urgency)
● Weaker urinary stream (inc. nocturia)
● Loose/irregular bowel movements
■ Long term
● Much less common than early effects, but more serious and longer lasting
● Urinary stricture or incontinence are rare
● Loss of potency (can Tx with PDE-5 inhibitors)
● Proctitis
○ Prostate seed brachytherapy or high dose radiation
■ Short term
● Perineal discomfort immediately after Tx
● Increased urinary frequency, urgency, weak stream and nighttime urination
○ Greatest 4-6/52 after therapy and dissipate over the following 3-6/12
■ Long term
● See external beam radiation long term SEs
● Androgen deprivation therapy
○ Background
■ Prostate cancer dependent upon androgen in most cases
● 90-95% oc circulating androgen is produced by testes
● Remainder is produced by the adrenal glands
● Regulated through hypothalamic pituitary axis
■ At the time of disseminated disease Dx, Tx is not curative
■ Systemic therapy indicated for:
○ Biochemical recurrence after definition therapy (e.g. RRP/RT)
○ Primary disseminated prostate cancer
○ Two methods for ADT
■ Surgical castration
● Bilateral (subscapular) orchiectomy
○ Simple and cost-effective procedure
○ Serum testosterone levels rapidly decreased to castrate levels
○ Still considered ‘gold standard’ for ADT against which Tx are rated
○ Only 22% of patients will choose orchiectomy above GnRH Tx
○ Drawbacks
■ Negative psychological effects
■ irreversible and does not allow for intermittent Tx
■ Medical castration/hormone therapy
● “Flare up” phenomenon due to temporary testosterone increase at initiation of Tx
○ Combination with an antiandrogen can prevent “flare up”
○ Combined approach sometimes used as long-term therapy to improve
efficacy of a GnRH alone
● 10% of patients fail to achieve castration levels
● Currently main form of ADT
○ Comparative results in overall survival between GnRH antagonist and
orchiectomy
● Hormones used:
○ LHRH agonists widely used to suppress androgen production
○ Antiandrogens
 ○ LHRH antagonists
○ SEs
■ Short term: castration syndrome
● Sexual dysfunction
● Decreased Muscle Mass
● Increased ratio of fat to lean body mass
● Decrease in Bone Mineral Density and/or Osteoporosis
● Decreased body hair
● Decreased hematopoiesis
● Poor ability to concentrate
■ Long term:
● Peripheral insulin resistance
○ Decrease whole body insulin sensitivity index (WBISI)
○ Increased fasting insulin
○ Increased OGTT
○ Increased Hb1AC
● Sarcopenic obesity
○ Decreased lean mass
○ Increased fat mass
○ Increased BMI
○ Increased weight
■ Other SEs
● Metabolic
syndrome
● osteoporosis/
fracture
● Anaemia
● Alteration in lipid
profile
● Depression,
personality change
● Tx of castration-resistant prostate cancer
○ Abiraterone
■ Inhibits androgen
production at all there
sources

○ Enzalutamide
■ AR signalling inhibitor that inhibits AR signalling in three ways
● Block AR bindings
● Impair nuclear translocation
● Block DNA binding and activation
○ Docetaxel better than mitoxantrone
■ PSA reduction >50%
■ Pain reduction significant
■ Improvement in QoL
■ Improve overall survival - 18.9/12 vs 16.5/12
■ Toxicity
● Neutropenia (32%), alopecia (65%), diarrhoea (32%)
● Mx of metastatic castration-resistant prostate cancer
○ Symptomatic control of bone mets
○ Radium -223 acts as calcium mimetic
■ Naturally targets growth in and around bone mets
■ Excreted by small intestine

Monitoring
● Blood pressure
● Fat mass (abdominal perimeter or impedance technique)
● Cholesterol total and HDL
● Fasting glucose/ HbA1c
 ● Triglycerides
● Bone density
● Psychological assessment

Prognosis
● Relapse
○ Often detected by rising PSA
○ Can consider salvage Tx
○ Often incurable at this point but life expectancy remains long
● Prognostic factors in advanced disease
○ PSA >114 ng/ml
○ PSA doubling time <55 days
○ Presence of visceral metastases
○ Pain
○ Anaemia
○ Bone scan progression
○ (Overall survival is halved in presence of 3-4 of the above)

Year 4 Medical Student Oncology Tutorials 2015/16

Prostate cancer – Case 1

Case and questions given to the students

A 60 year old gentleman presented to the GP with frequency and occasional feeling of incomplete emptying. Urine was
tested to rule out infection and he had a blood test for PSA. This came back as 6.5 and the patient was referred to
urology for investigations for prostate cancer.

PSA can go up with prostatitis, digital rectal exam…

● PSA risk:
○ <10 ng/l = low risk
○ >20 ng/l = high risk

1. What are the relevant investigations?

● MRI prostate and pelvis: stage, localise (what area to target)
○ Pelvis for LN involvement
● Trans-? ultrasound
The histology was reported as Gleason Score 6 involving 1/14 cores involving less than 5% of the core.

2. What is Gleason Score? How is it calculated?

● 3+3 = low risk prostate cancer
Gleason score:
● </6 = low risk
● 8-10 = high risk
On clinical examination there was no evidence of extension beyond prostate. The findings were confirmed on MRI of
pelvis. Bone scan was negative for metastatic disease.

3. What are the different risk groups for early prostate cancer? How are they categorised?
●
4. What are the treatment options for the above patient? What are the advantages and disadvantages? Which
is the preferred option?
● Radiotherapy
● Prostatectomy
● Do nothing - i.e. active surveillance!!
○ Avoid SEs
● ADT can be as a neo-adjuvant before surgery

If patient is going to live less than 10 years - offer radical Tx (generally speaking)

HIFU - for low risk prostate cancer

Patient underwent radical prostatectomy. The histology came back as T3a disease with positive margins(bad!).
Positive margins = microscopic disease

1. What are the options for further management?

Year 4 Medical Student Oncology Tutorials 2015/6

Prostate cancer – Case 2

Case and questions given to the students

A 67 year old man presented to GP with history of back pain. X-ray showed sclerotic changes in spine suspicious of
metastatic disease. On further investigation his PSA comes back as 256.On examination he has a hard irregular
prostate. His bone scan shows extensive metastatic disease involving the spine and the rib cage.

1. What is the most likely diagnosis?

● Prostate cancer
1. How will you treat this patient? What are the main side effects of the treatment?
● Androgen deprivation - ADT
○ Give biceriline(?) 4-12 weeks as a depo
● Steroids - pred or high dose dexamethasone
○
After 9 months treatment his PSA has come down to 1.7. He continued on treatment. 2 years later PSA started to go
up again and reached 30.

1. What is the next option to control his prostate cancer?

● Enzalutamide
His PSA improved with addition of the new tablet. But 6 months later it again started to rise.

1. What are the further treatment options? What is the role of chemotherapy in prostate cancer?
● Chemo - docetaxel
He starts on chemotherapy. 2 months later he presents to A&E unwell with fever and chills.

1. What is the likely diagnosis? How will you manage? How can you avoid it happening with next cycle of
chemotherapy?
●
He decided to discontinue chemotherapy. 2 months later his back pain worsens and is prescribed stronger analgesics
by the GP. The pain improves on analgesics initially but 6 weeks later he presents to the A&E with worsening of pain,
weakness in his legs (grade 4 power) and difficulty to walk.

1. What is the likely diagnosis? What is the investigation of choice? How will you manage this complication of
metastatic prostate cancer?
● Radium-223 (or strontium)
○ Localises to bones
○ SEs
■ Haematological problems - neutropenia, thrombocytopenia...