Head & Neck Cancer (HNC): Curative Treatment with Radiotherapy and Chemotherapy

A pleasant lady, 53 years old with long standing hypertension, presented with dysphagia symptom for 3 months duration.

She was diagnosed with base of tongue SCC, T2N2M0.

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Image for illustration purpose only

Discussion in multidisciplinary team (MDT) meetings

  • Surgery or definitive concurrent chemo-radiotherapy (CRT)?
  • Surgeon want to operate, I want definitive concurrent CRT (happen all the time, ha3)
  • Rationale? With surgery, the risk of morbidity (possible mortality) and organ dysfunction (swallowing, speech).
  • Also, post-op, patient will still need adjuvant treatment (radiotherapy +/- chemotherapy) due to stage of the disease.
  • So, why subject patient to three different treatment modalities (surgery, radiotherapy, chemotherapy) when patient just need two (radiotherapy, chemotherapy) modalities to achieve similar results.
  • Surgery can be kept for salvage treatment in future if disease recur.
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Image from ‘Open access atlas of otolaryngology, head & neck operative surgery’ (J Fagan, ‎2014)

Patient (usually the best person to break the deadlock) was not keen for surgery. Unfortunately, she just want radiotherapy and not chemotherapy initially.

Fortunately, she agreed for concurrent CRT after advice.

  • What are the benefit of definitive concurrent chemo-radiotherapy (CRT)?
  • What other option does she have? Concurrent bio-radiotherapy (BRT)?
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Optimising radiotherapy treatment. Although radiotherapy is an effective treatment by itself, more can be done to improve cure rate, survival and local control for head and neck cancer, especially those at later stage of the disease.

Concurrent chemo-radiotherapy (CRT)

Evidence from multiple clinical trials involving thousands of patients support the use of concurrent chemo-radiotherapy because the proven improvement in survival and loco-regional control.

The chemotherapy used is either cisplatin or 5FU-carboplatin (for patients who unable to  tolerate cisplatin) combination. These chemotherapy are widely available and affordable.

Absolute survival gained in 5 years was 6.5% compared to radiotherapy treatment alone.

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Survival curves in concurrent chemo-radiotherapy arm for all trials. Absolute benefit in survival was 6.5% in 5 years. (JP Pignon, ‎2009)

Patients also need not afraid of chemotherapy causing harm to them because chemotherapy had been proven (see image) to be effective in reducing cancer death but does not contribute to non-cancer death.

My patients finally agreed for definitive concurrent CRT. I hope this can reassure other patients too who are afraid of chemotherapy. Chemotherapy saves life.

Screen Shot 2018-08-09 at 1.55.57 PM.png
The above showing non-cancer death and cancer death survival curves in the recent trials comparing concurrent chemo-radiotherapy with radiotherapy only. Improvement in survival was due to reduction in head and neck cancer death for patients who underwent concurrent chemo-radiotherapy. Addition of chemotherapy did not cause any additional non-cancer death. (JP Pignon, ‎2009)

Concurrent bio-radiotherapy (BRT)

Fortunately, there is an alternative for those who are still worried and not keen for chemotherapy.

Concurrent bio-radiotherapy is substituting chemotherapy with an effective biologic therapy.

The evidence for bio-radiotherapy in head and neck cancers (oropharynx, larynx and hypopharynx only) came from one phase III clinical trial:

  • Radiotherapy plus cetuximab vs radiotherapy alone. (JA Bonner, ‎2006)
  • Average/ median duration of locoregional control was 24.4 vs 14.9 months for patients treated with cetuximab plus radiotherapy and radiotherapy alone, respectively
    • 2-year loco-regional control rate (50% vs 41%) and 3-year loco-regional control rate (47% vs 34%)
Screen Shot 2018-08-09 at 2.45.43 PM.png
Kaplan–Meier Estimates of Locoregional Control among All Patients Randomly Assigned to Radiotherapy plus Cetuximab or Radiotherapy Alone. (JA Bonner, ‎2006)
  • Average/ median duration of overall survival was 49.0 vs 29.3 months
    • 3-year survival rate (55% vs 45%) and 5-year survival rate (45.6% vs 36%)
Screen Shot 2018-08-10 at 2.41.31 PM
Kaplan–Meier Estimates of Overall Survival among All Patients Randomly Assigned to Radiotherapy plus Cetuximab or Radiotherapy Alone. (JA Bonner, ‎2006)

Absolute survival gained in 5 years was 9.6% compared to radiotherapy treatment alone.

Although the results were positive, the comparator arm for this study was with radiotherapy alone and not concurrent chemo-radiotherapy (gold standard).

The advantage of this treatment is the tolerability and minimal serious side effects.

Side effects

Obviously, with more treatment, there will be more side effects.

There are more acute (occur during treatment) side effects in the combination treatment (CRT/ BRT) as compared with radiotherapy alone.

However, acute side effects such as mucositis, skin desquamation, diarrhoea, nausea, vomiting, anaemia and infection are mostly mild and manageable if identified and treated early.

Late toxicities (side effects that occur after completion of radiotherapy) are mainly due to radiotherapy, not chemotherapy. With improvement in radiotherapy technology and techniques (more on this on later postings), late toxicitiescan be reduced significantly.

Finally

Concurrent CRT/ BRT offers patients an effective treatment against head and neck cancers and should always be offered as an option to patients besides surgery.

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