Non-operative Management of Cancer

Question 1

Non small cell lung cancer: adjuvant therapy

Answer 1

Post-operatively
- Chemotherapy - to increase chance of cure/reduce risk of recurrence
- Stage IB and II – adjuvant cisplatin+vinorelbine improves 5-year survival by 4.5% at 5 years
- RT – Adjuvant RT detrimental in stage I and II; some benefit possible if mediastinal nodes (N2) or involved margins

Question 2

NSCLC: NEOADJUVANT THERAPY

Answer 2

Pre-operatively

• Not used in clinical practice
• Stage III: preoperative chemotherapy demonstrated some advantages
  
  • No NA chemo in stage I/II
• There may be a role for targeted treatment/IO neo adjuvantly in the future

Question 3

NSCLC: RADICAL RADIOTHERAPY

Answer 3

• Patients reviewed in clinic to assess fitness and discuss plan. Then attend for RT planning scan
  
  • Planning process takes around 2 weeks
  • Treating all involved areas of disease
    
    • As much of prescribed dose to disease as possible. Minimum dose to surrounding structures
• Variety of regimes:
  
  • 55Gy in 20 fractions: treated daily Monday–Friday for 4 weeks
  • 54Gy in 36 fractions: treated three times daily for 12 consecutive days
• Side effects:
  
  • Acute: lethargy, oesophagitis, SOB due to pneumonitis
  • Long term: pulmonary fibrosis, oesophageal stricture, cardiac
• 5-year survival rate around 20%
• Pulmonary function tests essential
  
  • Poor lung function (typically FEV1 < 1 or <50% pred) precludes radical RT

Question 4

NSCLC: CONCURRENT CHEMORT

Answer 4

• Chemotherapy is systemic treatment
• Survival better than with RT alone (median survival 9/12 versus 13/12)
  
  • 4-5% overall survival benefit at 5 years
• Addition of chemotherapy increases toxicity
  
  • Nausea, GI upset, marrow suppression and risk of life threatening infection, VTE disease, neuropathies
• No standard chemo regimen:
  
  • Most centres use a doublet regime
  • Each cycle 21 days
• Radiotherapy planning process the same
  
  • Typically start radiotherapy with cycle 2 of chemotherapy
• 2-year survival ~27%
• Can give sequential chemotherapy, then radiotherapy

Question 5

NSCLC: PALLIATIVE TREATMENT

Answer 5

Palliation essential. Options include:

• Chemotherapy
  
  • Median survival now >12 months with chemo alone
• Immunotherapy
• TKI
• Palliative radiotherapy
• Combination of above

Question 6

NSCLC: PALLIATIVE CHEMOTHERAPY

Answer 6

• Given as a doublet regime
  
  • Two drugs given as IV infusion every 3 weeks
• 3 as good as 6 cycles of chemo
  
  • Most centres give 4 cycles
  • Then maintenance chemotherapy with Pemetrexed improves survival by further 3 to 5 months
  • Regular CT scans to ensure ongoing response
• Quality of life should be measured
• 2nd line chemotherapy options available but depends on patient fitness

Question 7

NSCLC: PALLIATIVE IMMUNOTHERAPY

Answer 7

• New(ish) treatment modality
• PDL1 (programmed death ligand) – protein that prevents immune system attacking cells in the body
• Cancers god at masking themselves from immune system via PDL 1 expression
  
  • Immunotherapy works by upregulating immune system and ‘unmasking’ cancers
• Can be used first line if PDL1 score >50%
  
  • Otherwise, can be used second line

Question 8

NSCLC: PALLIATIVE TKIS

Answer 8

• Suitable for patients unfit for chemotherapy (PS 0-3)
• Second line treatment options at progression (docetaxel+/- nintedanib, pemetrexed, erlotinib)
• Understanding mechanisms of resistance - REBIOPSY

Question 9

NSCLC: PALLIATIVE RADIOTHERAPY

Answer 9

Management of symptoms:

• Bone metastasis
• Cord compression
• Haemoptysis
  
  • Typically a single or up to 5 fractions total

High dose palliative:

• If disease too large to encompass radically
• Has a survival advantage

Question 10

SCLC: LIMITED DISEASE

Answer 10

• CRT curative treatment
  
  • Followed by prophylactic cranial radiation (PCI)
• Combination of drugs eg. cisplatin+ etoposide
• No advantage from
  
  • High dose chemo
  • Alternating chemo
  • Maintenance chemo
  • Chemo ‘on demand’
  • Maintenance Interferon, MMPI, targeted therapies
  • A MAJOR CHALLENGE!

OUTCOMES!!!

• Response rate 90%
• Complete remission ~60%
• Median survival (MS) with no treatment ~8 months
• MS with treatment ~16 months
• 2-year survival ~25%
• Second line therapy suboptimal

Question 11

SCLC: EXTENSIVE DISEAS

Answer 11

• 4 cycles only of combination chemotherapy
• Consolidation thoracic RT
• PCI recommended (NEJM 2007)
  
  • (prophylactic cranial irradiation)
• Consider RT to palliate symptoms if not fit for chemo
• Brain metastases? RT and steroids

OUTCOMES

• Response rate ~80%
• CR in ~30%
• Median survival with no treatment is ~8 weeks
• Median survival with treatment is ~8 months

Question 12

Side effects of chemotherapy

Answer 12

• Marrow suppression (+ risk of life threatening infection)
  
  • Neutropaenic sepsis
• Nausea. Vomiting. GI upset. Mucositis. Fatigue. Lethargy.
• Neuropathy. Increased risk MI/stroke. Renal impairment.
• Hair loss. Nail changes

Question 13

Side effects of radiotherapy

Answer 13

• General: Lethargy. Risk to surrounding organs
• Acute: pneumonitis. Dysphagia
• Late: Fibrosis. Stricture. Increased risk MI. 2nd malignancies

Question 14

Side effects of immunotherapy

Answer 14

Commonly: colitis, pneumonitis, dermatitis, endocrinopathies

Question 15

Lung cancer screening

Answer 15

• At risk population
• Low dose CT
• Radiation risk to population ?secondary cancers
• Logistical challenge
  
  • Machine time
  • Reporting scans
  • Stress of false positives
  • Lung nodules needing followed up
• Screening is coming. Possibly will be combined with smoking cessation interventions