Lung Cancer

is the most common cancer worldwide, and also the greatest cause of cancer-related deaths. Through the course of the twentieth century the incidence of lung cancer increased steadily, but due to improved public awareness and fewer people smoking, the number of cancer related deaths have started to decline.

Screening

The National Lung Screening Trial in the USA compared CT screening with CXR in patients who are at risk of developing lung cancer. In this trial, CT-screened individuals showed a 20% reduction in lung cancer mortality compared to those screened with CXR only. This trial identified the ideal candidates for screening as asymptomatic patients between 55 and 77 years, who have a smoking history of at least 30 pack-years, and (if not smoking any longer) have not quit smoking more than 15 years before screening starts.

Pathology

Up until about a decade ago, the clinician based treatment decisions on TNM stage and whether the tumour was a small-cell (SCLC) – roughly 15% of all lung cancer – or non-small-cell lung cancer (NSCLC). For NSCLC, we now know that there is an important difference between adenocarcinoma (about 45%) and squamous cell carcinoma, and as such patients with stage IV NSCLC receive different treatments. Routine analysis to identify specific mutations (including epidermal growth factor receptors(EGFR) and anaplastic lymphoma kinase (ALK) receptors in adenocarcinoma) for which targeted therapies are available, make it possible to tailor patients’ treatment and optimize responses.

Treatment

General

A very brief outline of general guidelines will follow. Exciting new developments in the fields of targeted and immune therapy in recent years give hope of improving the low survival rate (around 15% at five years) for stage IV disease, but however are out of the scope of this article.

Stage I and II

These are ideally treated surgically. The preferred procedure is a lobectomy with lymph node dissection of the unilateral mediastinal nodes. For pathological stage II and some IB tumours, adjuvant chemotherapy is indicated. Radiation therapy reduces local recurrences where margins are involved microscopically. When lymph node metastases are found (pathologic stage III), adjuvant chemotherapy followed by radiation is indicated.

For patients who are unfit for surgery, radiation therapy is an alternative treatment. Stereotactic body radiotherapy (SBRT) can deliver a few high doses of radiation to a precisely localized target, resulting in a highly effective ablative treatment. Where this technology is not available, more conventional methods of external beam radiotherapy (RT) are used commonly with satisfactory results.

”At DMO, we have stereotactic body radiotherapy treatment available at both our Sandton Oncology and Groenkloof Radiation Oncology units.”

Comparisons with historic data show that conventional RT yields inferior survival rates compared to surgery (30-50% vs. 50-70% for stage I at 5 years). To date no head-to-head comparisons are available to compare SBRT and surgery, and even though SBRT is superior to RT, surgery should still be the treatment of choice for operable stage I and II patients.

Stage III

Stage III disease is defined as either a locally advanced tumour (T3 and T4), and/or patients with mediastinal lymph nodes, in the absence of metastases. This is a heterogeneous group of patients, and the fact that staging systems have changed over the years make it difficult to extrapolate historical data to make treatment decisions. International guidelines are available to assist clinicians in the management of patients.

One of the most critical steps in devising a management plan for the stage III patient is accurate nodal staging. This is a particularly involved process, and should ideally be carried out by a surgeon with experience in lung cancer management. Imaging is used as a starting point to determine the exact surgical work-up a patient will need, as some stage III patients may still be candidates for radical surgery.

Concurrent chemo-radiotherapy is the treatment of choice for most patients who are not surgical candidates. These patients receive a platinum-based regimen and standard dose RT. This approach has been shown to achieve better survival compared to sequential treatment (chemo followed by RT). For patients who are not medically fit to tolerate chemotherapy, RT can offer effective palliation of symptoms and a modest improvement in survival.

Stage IV

Patients with advanced, metastatic lung cancer are considered incurable and unfortunately have a poor prognosis. The aim of treatment is to prolong life if possible, address symptoms due to the disease, maintain a good quality of life and limit the adverse effects caused by treatment.

The following factors are considered when devising a treatment strategy:

• The disease burden – how many sites of metastases are present and how symptomatic the patient is
• Histologic type – squamous vs. adenocarcinoma
• Molecular findings – the presence of mutations such as EGFR and ALK
• Programmed death ligand 1 (PDL-1) expression (high)

After progression on one line of treatment, several further options are available depending on initial therapy and above-mentioned factors.

Radiation therapy can be of benefit to stage IV patients in the following situations:

• Limited metastases (oligometastatic): SBRT can offer effective control of a single area of recurrence or metastasis.
• Bone metastases: RT is highly effective to relieve pain caused by bone metastases.
• Brain metastases: Whole brain radiotherapy can offer patients relief from headache, nausea, and pressure effects of intracranial tumours, but is often associated with long-term cognitive decline. In the case of few brain metastases as well as good control of the local lung tumour and no other spread, stereotactic radiotherapy can be used to treat the brain lesion(s) only and spare the patient the effects of whole brain irradiation.

Surveillance

Follow-up is crucial both in successfully treated localized tumours as well as patients with metastatic disease. In case of the former, early detection of recurrence can allow for more effective salvage therapy, and to start earlier with systemic therapy for metastatic disease can potentially prolong a patient’s life. In case of the latter, it is beneficial to start with alternative systemic therapy as soon as progressive disease is evident.

Patients come for follow-up visits and CXR every three months and an annual CT scan. PET-CT can also be considered. After two years less frequent follow-up (6-monthly) is sufficient. When patients exhibit clinical symptoms and signs of bone or lung metastases, a bone scan or brain CT scan is appropriate.

Conclusion

• Lung cancer is a common malignancy, with personal or second-hand smoke being a major risk factor. The primary care doctor should discourage youngsters to start and encourage smokers to stop smoking as a preventative strategy.
• For patients who have a strong smoking history and are asymptomatic, screening CT scan of the chest should be considered.
• The best outcomes are in patients with stage I and II disease who are able to undergo curative surgery and adjuvant therapy as indicated.
• For most stage III patients combined chemo-radiotherapy is the preferred treatment strategy.
• Radiation therapy is an effective alternative for patients who are medically unfit for surgery and/or chemotherapy. Stereotactic body radiotherapy can offer high doses of precisely localized radiation to selected tumours.
• Stage IV patients are considered incurable and the aim of treatment is to maintain quality of and limit treatment side-effects. In many cases treatment may also provide longer survival to patients.
• Radiotherapy can offer durable and effective palliation of bone metastases.
• Brain metastases can benefit from radiotherapy to improve symptoms of headache and obstruction.
• In the case of limited brain-only lesions, stereotactic radiotherapy can spare patients from cognitive decline while still controlling the tumour.

Sources:

1. UpToDate website
2. Handbook of Evidence-Based Radiation Oncology, 2nd edition; Eric K. Hansen and Mark Roach III (editors)

Dr Maryke Etsebeth

22 September 2017