Clinical Oncology SC014: The War Against Cancer

Question 1

Global burden of cancer

Answer 1

2018:
- 18.1 million new cases
- 9.6 million deaths
—> Projected 29 million new cases in 2040

Sustainable development goals (SDGs) set by UN in 2015:
- ↓ 1/3 premature death from NCD through prevention + treatment
—> Cancer, CVS, Respiratory disease

WHO:
- ↓ 25% premature death by 2025
—> by ↓ risk factors

Comprehensive cancer control strategy + action plan:

1. Prevention
2. Early detection
3. Diagnosis + Treatment
4. Palliative care + Survivorship

Question 2

Cancer burden in HK

Answer 2

Total no. of new cases: 34028
Total no. of deaths: 14209 (31% of all deaths: Top killer in HK is cancer)

Use age-standardised rate for incidence:
- more accurate way to measure success of intervention
- ∵ age composition of society change with time
—> aging population will have more cancer incidence

Nasopharyngeal cancer:
- ↓ trend in HK

Male:
- No. of cancers ↓

Female:
- No. of cancers ↑

Question 3

HK Cancer Strategy 2019

Answer 3

1. To reduce incidence + mortality of cancer
2. To adopt a holistic approach for cancer care
3. To improve ***QoL of patients through better access to evidence-based prevention, screening, early detection + diagnosis, effective treatment + palliative care
4. To transform concept of care for survivors + perceive cancer as a chronic illness
5. To capitalise on innovation, technology, surveillance system, scientific research

Question 4

Principles in War against cancer

Answer 4

1. Prevent the preventable
2. Treat the treatable
3. Palliate the incurable

Question 5

Cancer prevention

Answer 5

• > 1/3 cancers preventable

Risk factors:

1. UV light
   - >90% of skin cancers preventable by sun protection
   - avoid using artificial UV for tanning
2. Smoking
   - associated with 17 different cancers
   - MPOWER: Monitor, Protect, Offer, Warn, Enforce, Raise (tax level recommended: 70% of retail price)
3. Infections
   - H. pylori: Gastric cancer
   - HPV: Cervix, Oropharyngeal cancer
   - HBV, HCV: Liver
   - EBV: Nasopharyngeal cancer
   —> ***Vaccinations
4. Unhealthy diets / Obesity / Physical inactivity
   - ↑ Risk of 13 types of cancer
   - Red meat, processed meat, salted fish, aflatoxins
5. Alcohol
   - 4.2% of cancer deaths attributed to alcohol
   - problem: no threshold established
6. Reproductive / Hormonal factors
   - Breast cancer
   —> ↑ risk: HRT, OC pills
   —> ↓ risk: Childbearing, Breastfeeding
7. Occupational carcinogens + Environmental pollutants

Question 6

Recommendations from CHP to reduce cancer risk

Answer 6

1. Quit smoking
2. Reduce alcohol intake
3. ↑ Fruit + vegetable, ↓ Red / processed meat
4. Vaccination
5. Avoid over exposure to UV
6. Breastfeed
7. Appropriate regular exercise
8. Maintain healthy body weight

General recommendations on healthy lifestyle to prevent cancer:

1. No smoking
2. Maintain weight: BMI 18.5-22.9
3. Maintain regular physical activity
   - 150 mins moderate activity / 75 mins vigorous activity per week
4. Limit alcohol
   - <=2 drinks (men) / 1 drink (women)
5. Healthy diet
   - >=3 portions of fresh vegetables + 2 portions of fruits
   - <=500g red meat per day + avoid processed meat
6. Avoid over exposure to UV

Question 7

Early detection of cancer

Answer 7

1. Screening of asymptomatic people
   Principles of cancer screening:
   - Well-recognised natural history of the condition: development from latent to confirmed malignancy
   - Effective treatment for detected cancer
   - Suitable test / examination with high level of accuracy

Population screening:

• Cancer should be an important health problem
• Cost-effective analysis consideration: Cost of screening (including Dx + Tx) should be economically balanced in relation to possible Expenditure on medical care as a whole

2. Alertness to presenting features
   - enhance public education of symptoms of common cancer

Question 8

Advantages + Disadvantages of cancer screening

Answer 8

Advantages:

• Better outcome
• Less radical treatment needed
• Reassurance for those with true negative results
• Psychological benefit to population
• Savings may occur because treatment for early stage screen-detected cancer may be less complicated

Disadvantages:

• Longer morbidity if prognosis is not altered
• Over treatment of borderline abnormalities
• False reassurance for those with false -ve results
• Unnecessary investigations of false +ve results
• Resource costs of screening system
• SE / complications of invasive investigations

Question 9

Colorectal cancer

Answer 9

Prevention measures:

1. Healthy diet
   - ↑ fruit + vegetable (daily intake of 25g fibre / 5 portions of fruit + vegetable)
   - ↓ red + processed meat
2. ↑ Physical activities
3. Maintain health body weight
4. Avoid / quit smoking
5. Limit alcohol consumption

Screening:

• ***Whole population aged 50-75 yo (Strongly recommended)
• launched in 2016
• 3 year pilot programme
• FOBT: subsidy $280 / case
• Colonoscopy: subsidy $7800-8500 / case

1. Faecal occult blood
   - ↓ incidence 5%
   - ↓ mortality 14%
   - relatively cheap, easy to do, non-invasive
   - positive tests —> complete colonic evaluation (ideally colonoscopy)
   - Faecal immunochemical test (FIT) preferred to chemical test ∵ **fewer false +ve + more **specific to colon
   - Sensitivity limited ∵ many CRC only bleed ***intermittently
2. Sigmoidoscopy
   - ↓ incidence 18%
   - ↓ mortality 28%
   - Flexible sigmoidoscopy (FS) every 5 years
   —> simple, no sedation needed
   —> once-only flexible sigmoidoscopy screening for 55-64 —> substantial + long-lasting benefit for CRC: ↓ incidence 33% + ↓ mortality 43%
   - limitations: Rectum + Sigmoid only account for ***~60% of CRC
3. Colonoscopy
   - every 10 years (take long time to develop from polyp to cancer)
   - significant impact shown by case-control + cohort studies
   - sensitivity >90% + specificity >99%
   - ***polypectomy: >50% ↓ in CRC incidence
   - limitations:
   —> no RCT yet to demonstrate ↓ mortality
   —> sedation needed

Question 10

Cervical cancer

Answer 10

Carcinogenesis / Natural history:

• ***Orderly sequence
• ***Long latency
• Lifetime risk of acquiring at least 1 HPV infection estimated >90%
• Majority of these infections are transient
• > 100 HPV types, 13 associated with cervical intraepithelial neoplasia
• Most HPV infection never progress beyond low grade disease (CIN 1)
• 80-90% of low grade cervical abnormalities regress spontaneously
• Orderly Progression:
  HPV infection —> high grade lesion —> invasive cancer

Prevention measures:

1. Preventive vaccine before becoming sexually active
2. Practice safe sex
3. Avoid or quit smoking
4. Healthy diet: rich in fresh fruit & vegetables

Screening:
Strongly Recommended:
- Female population aged 25-64 years
—> as soon as start sexual activity
—> Vaccination does NOT substitute for Screening (∵ vaccine cannot prevent all cervical cancer (cannot cover all HPV strains))

Local cost-effectiveness analysis:
- organised screening with conventional cytology every 3 years produced >90% ↓ in lifetime risk of cervical cancer compared to no screening

• **Current Recommendation in HK:
• ***Cervical smear (liquid-based Pap) at 3-yearly intervals after 2 consecutive normal annual smears (1, 1, 3-yearly cycle)

Presentation pattern by stage in HK:

• 32% stage I & 30% stage II at diagnosis (2015)
• screening programme now still not well-used esp. by high risk groups (e.g. sex workers)

Question 11

Other screening test: HPV DNA test

Answer 11

Advantages:

1. Self testing
   - patient collect vaginal sample herself & then send sample to lab
2. High sensitivity for detecting HSIL
   - compared with Pap smear test, HPV DNA test is **more sensitive for HSIL but **less specific
   - sensitivity as high as 90% with a specificity of 50-70%
3. HPV can precede cytology changes
   - persistent HPV infection may progress to LSIL then —> HSIL
4. Potential spacing of screening
   - from 3 to 5 years

• Evidence suggest that HPV DNA testing in conjunction with Pap smear cytology may improve screening efficacy & further reduce mortality
• Main challenge is to find a good triage method to select patients for ***colposcopy

Question 12

WHO pledge to eliminate cervical cancer globally by 2030

Answer 12

WHO target 90:70:90

• 90% coverage of HPV vaccination of girls <15
• 70% coverage of screening (70% women screened with high-performance tests by 35, 45) + 90% treatment of precancerous lesions
• Management of 90% of invasive cancer cases

Target:
- 30% ↓ in mortality from cervical cancer

Question 13

Breast cancer

Answer 13

Prevention measures:

1. Maintain healthy body weight
2. ↑ Physical activities
3. Limit alcohol consumption
4. Healthy diet
   - ↑ Consumption of fruit & vegetable (daily intake of 25g fibre / 5 portions of fruit & vegetable)
5. Cautious about post-menopausal replacement using combined estrogen-progestogen hormone
6. Consider earlier childbirth
7. Consider breastfeeding for longer duration

Screening:

1. Breast self-examination (BSE)
   - low sensitivity
   - **no reduction in mortality / improvement in stage distribution
   - **insufficient evidence —> still should encouraged —> familiar with their breast to report any obvious / persistent changes promptly
2. Clinical breast examination (CBE)
   - sensitivity 54% + specificity 94%
   - lack of RCT, ***insufficient evidence
   - Cochrane review: screening by BSE / CBE could not be recommended at present
3. Mammography (MMG)
   - sensitivity 83-95%, false positive 0.9-6.9
   - 20% ↓ mortality by routine screening
   - screenee ≥50 yr: higher sensitivity & greater mortality ↓
   - 15% relative (0.05% absolute) risk reduction
   - Over-diagnosis & over-treatment 30% (0.05% absolute risk increase)
   - more difficult in Chinese population
   —> ∵ **lower incidence than USA
   —> ∵ **dense breast (difficult mammogram interpretation)
   - ***no significant ↓ in breast cancer mortality in adequately randomised trials
   —> still many countries recommend ∵ big health problem

Mammography in HK
- Insufficient evidence to recommend for or against population-based mammography screening for general female in Hong Kong

Recommendation by HK Anti-cancer Society:

• Consider screening at least for high-risk cohorts (BRCA gene mutation / family of breast + ovary cancer)
• If screen, consider starting at age ***40 (18% of invasive cancer and 19% of carcinoma-in-situ patients aged ≤45 yr)
• Further ***cost-effective analyses for general population

Question 14

Liver cancer

Answer 14

Prevention measures:

1. Preventive vaccine against HBV at birth
2. Safety measures against transmission of HCV through blood transfusions
3. Limit alcohol consumption
4. Avoid fermented peanut (aflatoxin)
5. Avoid or quit smoking

Screening:

• High-risk cohort - chronic hepatitis carrier & known liver cirrhosis
  1. Half-yearly USG + AFP
• ↓ HCC mortality by 37%

HK recommendation:
- Routine screening by AFP or USG for asymptomatic persons at **average risk is **NOT recommended

High risk patients:

• HBV carrier
• Known cirrhosis

Question 15

Lung cancer

Answer 15

Prevention measures:

1. Avoid or quit smoking
2. Healthy diet
3. ↑ Consumption of fruit & vegetable (daily intake of 25g fibre / 5 portions of fruit & vegetable)

Screening:
- Consider **low dose CT for **heavy smokers (CXR not sensitive enough)
(USPSTF 2013 recommends annual screening with low-dose CT in adults 55 to 80 yo who have a 30 pack-year smoking history, currently smoke or quitted within the past 15 years)
—> serious concern about cost-effective
—> no conclusion

Question 16

Prostate cancer

Answer 16

Prevention measures:

1. Healthy Diet
   - Low in meat & other fatty foods of animal origin may ↓10-20% incidence of prostate cancer
2. Chemoprevention?
   - preliminary evidence from RCT showed
   * **Finasteride 5mg daily ↓ incidence of prostate cancer, but insufficient evidence on ↓ cancer mortality

Screening:
- PSA
—> Controversial
—> generally NOT recommended for population screening

Asymptomatic men:

• PSA Screening generally ***NOT recommended
• Patients with prostate cancer tend to have higher serum level of PSA than normal
• However, PSA can also be raised in conditions (e.g. BPH, prostatitis, urinary tract infection)
• But 2/3 of men with elevated PSA do not have prostate cancer at biopsy

Question 17

***Summary of screening timetable

Answer 17

Male:

• 30: EBV blood test + nasopharyngoscopy (for family history of NPC)
• 30-40: AFP + USG (if hepatitis carriers)
• 50: FIT / FS / Colonoscopy

Female:

• 25: Pap smear, Get familiar with breast
• 30: EBV blood test + nasopharyngoscopy (for family history of NPC)
• 30-40: AFP + USG (if hepatitis carriers)
• 40: Mammography (every 1-2 years)
• 50: FIT / FS / Colonoscopy

Question 18

Treatment for cancers

Answer 18

Multidisciplinary cancer services:

1. RT
   - External
   - Brachytherapy
   - Radio-isotope
2. Systemic
   - Chemotherapy
   - Targeted
   - Hormonal
   - Immunotherapy
3. Surgery
4. Radiology imaging
   - Diagnosis + Stage
5. Pathology diagnostics
   - Diagnosis + Stage

Question 19

Accessibility to Timely Diagnosis and Treatment in HK

Answer 19

1. To monitor waiting time for all cancers
2. To set Targets
   - to work towards reducing waiting time (90th percentile) to ≤30 days
   - from 1st suggestive symptom to definitive diagnosis
   - from diagnosis to 1st definitive treatment
3. To enforce improvement actions by HA
   - **Advanced planning on manpower, hospital infrastructure & equipment
   - **Public–private partnership - expansion of subsidy to cover both essential investigations & treatment

UK: 90 day rule: <90 days from symptom onset to initiate treatment

Affordability of Expensive Cancer Treatment:

• **Financial hardship
• All essential medicine (by WHO) are available in public hospitals
• But many expensive items are categorized as ***self-finalized items (SFI)
• Subsidy limited to those eligible for **Samaritan / **Community Care Funds
• Heavy financial burden for vast majority of middle-class citizens

Actions:

1. To steadily increase the scope of coverage for expensive treatment
2. To enforce health insurance coverage for cancer treatment
3. To consider tax deductions for cancer treatment

Question 20

Palliative care / Holistic care for cancer survivors + carers

Answer 20

1. Inadequate psychosocial support by public institutes
   - Rising prevalence of cancer survivors, many have persistent impairments
   - Active rehabilitation needed to regain maximum functional capability
   - For patients with incurable cancer —> ↑ need palliative / end-of-life care
   - Essential drugs for pain & symptom relief are available in public hospitals
   - Psychosocial/spiritual support mainly by NGOs on a self-financing basis
2. No analyses on unmet needs of patients & carers

Actions:

1. To analyse unmet needs of cancer patients / survivors & carers
2. To enhance supports for holistic care, palliative / hospice care, psychosocial / spiritual support for patients & families

Question 21

War against NPC: Success story

Answer 21

Risk factor for NPC:
- Salted fish (Chinese style 梅香) —> Nitrosamine (Carcinogen)

Public education:

• Avoid frequent consumption of salted fish & preserved food, esp. to young children
• Eat more fresh fruit & vegetables

Subsequent changing epidemiology of NPC in HK:
- ↓ Incidence of NPC
—> correlated with ↓ salted fish, ↓ smoking, ↑ fresh vegetable

Prevention measures:

1. Avoid high consumption of Cantonese-style salted fish, esp. for young children
2. Healthy diet
3. ↑ Consumption of fruit & vegetable
4. Avoid / Quit smoking

Screening:

• Insufficient evidence for whole population
• Consider for High-risk cohort: **1st degree relative of NPC patients (>4 fold ↑ in risk)
  1. **EBV serology + Endoscopy
• EBNA1-IgA + VCA-IgA
• serology alone not sensitive: early cases may not be serology +ve

2. EBV DNA
   - not all are DNA +ve

Treatment:

• NPC ***highly curable by RT +/- Chemo (>95% if stage 1)
• but problem is ***Late presentation (only 19% present at stage 1 / 2)

Advancing RT techniques:

• Improving radiation dose distribution
• 2D conventional —> 3D conformal, Stereotatic —> Intensity-modulated, Tomotherapy / Volumetric arc

Question 22

Precision oncology

Answer 22

1. Immunotherapy + Targeted therapy
2. ↑ Use of genomics
   - Next Gen Sequencing (NGS) tests
3. Personalised dose consideration: genomic profile for tumour control
   - Genomic profile to predict intrinsic RT / Chemo sensitivity
4. Technological advances for precision RT
   - MRI era
   —> PET-MR
   —> MR-simulator
   —> MR-linac

• Particle beam RT era
  —> Proton
  —> Heavy ion
  —> Boron-Neutron capture therapy
• Advances in Radiobiology
  —> Hyperfractionation, FLASH RT

5. Artificial intelligence
   - Smart hospital
   - Virtual nurse
   - AI-based auto-contouring in RT
   - AI-based diagnosis
   - AI-based treatment recommendation
   - Clinical data mining