Lungekreft er en type kreft som er forårsaket av ukontrollert cellevekst i lungevev. Kreft som har sin opprinnelse i andre deler av kroppen og sprer seg (metastaserer) til lungene regnes ikke som lungekreft og bør navngis etter opprinnelsesstedet. Lungekreft er den nest hyppigst diagnostiserte kreftsykdommen og den viktigste årsaken til kreftdødelighet. Anslagsvis 2 206 771 mennesker ble diagnostisert med lungekreft i 2020 på verdensbasis [1].

5-års overlevelsesrate for personer med ikke-småcellet lungekreft, den vanligste typen lungekreft, er vanligvis mellom 11 % og 17 %; den kan være lavere eller høyere avhengig av type lungekreft og i hvilken grad sykdommen har spredt seg til andre organer [2]. Mange pasienter diagnostisert med lungekreft har allerede utviklet seg til avanserte stadier fordi disse kreftformene ofte ikke har noen merkbare symptomer og kan forveksles med vanlige sykdommer.

Medianalderen for pasienter med lungekreft er rundt 70 år. Tobakkseksponering er fortsatt den viktigste årsaken til lungekreft. Yrkeseksponering og luftforurensning kan også virke uavhengig eller sammen med tobakksrøyking i utviklingen av denne kreftsykdommen. Imidlertid er det absolutte antallet pasienter som utvikler lungekreft og aldri har røykt fortsatt høyt, noe som kan oppstå som følge av en genetisk disposisjon. Familiær lungekreft er mer kompleks enn andre familiære kreftformer, og rollen til genetiske faktorer i utviklingen av lungekreft er fortsatt vanskelig å forstå [3, 4]. Vanlige symptomer på lungekreft er hoste, problemer med å puste, hoste opp blod, bryst- og/eller skuldersmerter, tretthet, vekttap og hyppige lungeinfeksjoner som ikke forsvinner eller stadig kommer tilbake. Ved mistanke om lungekreft utføres røntgenbilder, bildeskanninger samt blodprøver. En biopsi er en prosedyre som gjøres for å fjerne et lite stykke vev fra en svulst for å avgjøre om kreften er tilstede [5]. Det er to hovedtyper av lungekreft: 1. Ikke-småcellet lungekarsinom (NSCLC) som utgjør mellom 85 og 90 % av alle lungekrefttilfeller; og 2. Småcellet lungekarsinom (SCLC) som omfatter de resterende 10 % til 15 % av alle lungekrefttilfeller. Småcellet lungekreft har fått navnet sitt på grunn av at kreftcellene ser små og runde ut under et mikroskop mens ikke-småcellet lungekreftceller er større. SCLC vokser raskere enn NSCLC, og selv om de er mer responsive på kjemoterapi, er de fortsatt vanskeligere å behandle enn NSCLC [4, 6].

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NSCLC is categorised into five stages (0-4) depending on the extent of the disease. The stage describes where the lung cancer cells are located, the size of the lung cancer tumour and if it has spread to other parts of the body. The lower the stage, the less the cancer has spread, and the prognosis is better.

Stage 0: An early stage of lung cancer that is only in the top lining of the lung or bronchus and has not spread. 

Stage 1: The cancer has not spread to the lymph nodes or other parts of the body.

Stage 2: These tumours may be larger than those in stage 1 and/or have begun to spread to nearby lymph nodes. The cancer has not spread to distant organs.

Stage 3: Most commonly the cancer has spread to the lymph nodes in the mediastinum (the area in the chest between the lungs). 

Stage 4: The cancer has spread, or metastasized, to the lining of the lung or other areas of the body, most commonly the bones, brain, adrenal glands, and liver [7].

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Treatment of the patients with NSCLC depends on the stage, age, and performance of the patients. Treatment often involves combination of various approaches that may include surgery, radiotherapy, and systemic therapy such as chemotherapy, molecularly targeted agents, and immunotherapy.  

Surgery is recommended as the first treatment option in people with stage 1 or 2 NSCLC. Options for surgery include:

1. Lobectomy: a type of surgery that removes an entire section (lobe) of the lung (normally the right lung has three lobes while the left lung has two lobes.)

2. Segmentectomy or wedge resection: involves removing part of the lung but not an entire lobe.

3. Pneumonectomy: the removal of the entire affected lung. 

After surgery, radiation therapy may be recommended for patients with stage 1 or 2 NSCLC who have residual tumour at the operation area or patients who have higher risk of recurrence. Common radiotherapy methods for lung cancer treatment are:

1. External beam radiation therapy (EBRT): a type of radiation therapy that directs a beam of radiation from outside the body, toward the lungs or surrounding areas.

2. Stereotactic body radiation therapy (SBRT) also known as stereotactic ablative body radiation (SABR): a type of precision radiation therapy that involves delivering a high dose of radiation very accurately to tumours in the lung or other organs while limiting the dose to the surrounding healthy organs and tissues.

There is no single best treatment for people with stage 3 NSCLC. Therefore, recommendations should be individualized by a multi-disciplinary (specialty) team. However, the initial treatment for stage 3 NSCLC may include a combination of radiation therapy, chemotherapy, and/or surgery.

The identification of gene mutations in lung cancer has led to the development of molecularly targeted therapies to improve the survival of subsets of patients as personalised medicine alternatives. For instance, patients with stage 1 to 3 NSCLC who have mutation in a particular gene called EGFR can receive targeted therapy as part of their treatment. Immunotherapy is another alternative, in addition to conventional therapy, that may be offered to some patients with stage 2 to 3 NSCLC. This may be an option for patients whose cancer cells have programmed cell death ligand 1(PD-L1) on their surface.

Stage 4 NSCLC has already spread to other organs upon diagnosis and therefore, can be challenging to cure. Treatment options depend on where and how far the cancer has spread, whether the cancer cells have certain gene or protein changes and overall health. Targeted therapy is the main treatment option for such patients. The patients´ tumour will be tested for certain gene mutations (such as in the KRAS, EGFR, ALK, ROS1, BRAF, RET, MET, or NTRK genes). If one of these genes is mutated, the patient will likely receive targeted therapy. However, in patients who are negative for these mutations, PD-L1 expression status assists in decision-making for immunotherapy. Depending on PD-L1 expression status, patients might receive chemotherapy alone or in combination with immunotherapy.

Furthermore, surgery and/or radiation therapy can also be performed to treat areas of cancer spread (metastases) in addition to the cancer localised in the lung.

Recurrence

If the cancer continues to grow during treatment (progresses) or comes back (recurs), further treatment will depend on the location and extent of the cancer, what treatments have been previously given, and on the person’s overall health and desire for more treatment. Smaller cancers that recur locally in the lungs can sometimes be retreated with surgery or radiation therapy if it has not been already used before. Chemotherapy may be attempted if the cancer continues to grow after the initial treatment approach. If a cancer continues to grow during chemotherapy, other chemotherapy agents or targeted therapy can be administered. Immunotherapy can also be an option for patients who have not received it previously and can benefit from it depending on their PD-L1 expression status [8-11].

SCLC is historically categorized into two stages: limited and extensive. Limited stage lung cancer is in only one of the two lungs with or without spread to the lymph nodes located in the chest area between the two lungs. Extensive stage lung cancer has spread to tissue outside of the originally affected lung such as the opposite lung or distant organs [4].

Standard of Care  

Limited stage small cell lung carcinomas are generally treated with both chemotherapy and radiation therapy. Patients with extensive-stage small cell lung cancer are treated with chemotherapy alone or in combination with immunotherapy. Radiation therapy may also be beneficial in patients who respond to their initial chemotherapy.

Most people with limited-stage small cell lung cancer are treated with chemotherapy in combination with radiation therapy directed at the disease in the chest. Patients might also receive radiation therapy to some distant organs such as the brain to prevent the development of brain metastases and to improve survival. In rare patient cases with very early-stage disease where the only site of cancer is a single lesion within one lung, surgery is usually recommended. In such situations, surgery is then followed by chemotherapy with or without radiation therapy.

Patients with extensive-stage small cell lung cancer are generally treated with chemotherapy and immunotherapy. Surgery is not an option for patients with extensive-stage disease. Patients who respond well to chemotherapy may be given radiation therapy to the chest or to the brain to prevent further development of brain metastases [12].

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