**4. Indications of radiotherapy**

#### **4.1. Nonsmall cell lung cancer**

#### *4.1.1. Early stage I–II disease: curative treatment*

Radical surgery remained the preferred treatment in early stage I–II lung cancer with 5‐year overall survival rate of around 60–80%. Radical radiotherapy can be an alternative to patients who are medically unfit for surgery due to medical comorbidities or who declined surgery. Currently, there are no phase III trials to directly compare the outcomes after surgery with radiotherapy. Retrospective and historical databases showed that the long‐term survival after conventional radiotherapy may be half (or even less) than that after surgery, with 5‐year sur‐ vival of around 20–30% in most series. But this indirect comparison is difficult due to the dif‐ ferent population groups with more elderly, comorbidities, or poor lung function in those nonsurgical series. For elderly patients, hypofractionated scheme using 55 Gray (Gy) in 20 daily fractions is as effective as conventional radiotherapy in 2Gy per fraction.

Stereotactic body radiotherapy (SBRT) is now a newly emerging treatment option that allows delivery of a much higher radiation dose to a precise area than conventional radiotherapy. The reported local control rate in early stage lung cancer can be up to 80–90% in 2 years and is well tolerated. Therefore, it becomes the preferred radiotherapy modality for stage I lung can‐ cer patients who are not fit for surgery. But extra care should be given when treating tumors that are centrally located around the major airways due to the potential higher complications with the hypofractionated regime.

#### *4.1.2. Locally advanced stage III disease: curative treatment*

This stage of disease was considered locally advanced either due to extensive primary tumor extension to extrathoracic structures nearby (T3 or T4) or mediastinal lymph nodes involve‐ ment (N2 or N3). It is a heterogeneous population that requires multimodality treatments. The reported 5‐year survival was around 10–30%. A multidisciplinary discussion involv‐ ing cardiothoracic surgeons, radiologists, and oncologists is needed to individualize and optimize the treatment plan for each patient. Patients with good performance status 0–1, no significant weight loss of >10% in the preceding 3 months and good pulmonary function (forced expiratory volume in 1 second FEV1 > 1.0 L) are candidates for radical combined modality treatment.

For potentially operable N2 disease, induction treatment with either chemotherapy alone or chemoirradiation is recommended over surgery alone. There is no solid evidence to sup‐ port the superiority of either approach. Addition of preoperative radiotherapy may have the potential effect in downstaging the tumor and achieving a higher pathological complete remission rate of mediastinal disease. Special precaution should be given with its use in can‐ didates before a planned pneumonectomy due to the higher perioperative mortalities. When preoperative radiotherapy is considered, a dose higher than 45–54 Gy in 1.8–2 Gy per fraction had not been shown to give addition survival benefit.

For infiltrative N2 or N3 (contralateral mediastinum) disease, risk of systemic micrometasta‐ ses is high. Definitive chemoirradation is the commonly used approach. Addition of chemo‐ therapy to radical radiotherapy led to a survival benefit of 5–10% at 5 years. Concomitant use of chemotherapy had a further improvement in survival by 4.5% at 5 years when compared with sequential approach, but with the expense of higher toxicities (mainly esophagitis and/ or pneumonitis). Platinum‐based doublet chemotherapy is the preferred regime and usually 2–4 cycles are given [7, 8]. Thus, concurrent chemoirradiation is the preferred strategy for fit patients, while sequential approach can be used for less fit patients with disease still within a treatable radical radiotherapy volume. A dose higher than 70 Gy in conventional fractionation is not recommended due to the associated higher toxicities but no added survival benefit. A continuous, hyperfractionated, accelerated radiotherapy (CHART) using 54 Gy in 36 fractions of 1.5 Gy three times per day can be considered for selected patients opting for radiotherapy alone. It had around 20% relative risk reduction in 2‐year local progression rate and survival compared with conventional radiotherapy, but implementation can be challenging.

For patients with performance status 3–4, significant comorbidities and poor lung function that preclude a radical treatment approach, palliative radiotherapy may be considered for local symptoms control.

#### *4.1.3. Metastatic stage IV disease: palliative treatment*

**4. Indications of radiotherapy**

*4.1.1. Early stage I–II disease: curative treatment*

Radical surgery remained the preferred treatment in early stage I–II lung cancer with 5‐year overall survival rate of around 60–80%. Radical radiotherapy can be an alternative to patients who are medically unfit for surgery due to medical comorbidities or who declined surgery. Currently, there are no phase III trials to directly compare the outcomes after surgery with radiotherapy. Retrospective and historical databases showed that the long‐term survival after conventional radiotherapy may be half (or even less) than that after surgery, with 5‐year sur‐ vival of around 20–30% in most series. But this indirect comparison is difficult due to the dif‐ ferent population groups with more elderly, comorbidities, or poor lung function in those nonsurgical series. For elderly patients, hypofractionated scheme using 55 Gray (Gy) in 20 daily

Stereotactic body radiotherapy (SBRT) is now a newly emerging treatment option that allows delivery of a much higher radiation dose to a precise area than conventional radiotherapy. The reported local control rate in early stage lung cancer can be up to 80–90% in 2 years and is well tolerated. Therefore, it becomes the preferred radiotherapy modality for stage I lung can‐ cer patients who are not fit for surgery. But extra care should be given when treating tumors that are centrally located around the major airways due to the potential higher complications

This stage of disease was considered locally advanced either due to extensive primary tumor extension to extrathoracic structures nearby (T3 or T4) or mediastinal lymph nodes involve‐ ment (N2 or N3). It is a heterogeneous population that requires multimodality treatments. The reported 5‐year survival was around 10–30%. A multidisciplinary discussion involv‐ ing cardiothoracic surgeons, radiologists, and oncologists is needed to individualize and optimize the treatment plan for each patient. Patients with good performance status 0–1, no significant weight loss of >10% in the preceding 3 months and good pulmonary function (forced expiratory volume in 1 second FEV1 > 1.0 L) are candidates for radical combined

For potentially operable N2 disease, induction treatment with either chemotherapy alone or chemoirradiation is recommended over surgery alone. There is no solid evidence to sup‐ port the superiority of either approach. Addition of preoperative radiotherapy may have the potential effect in downstaging the tumor and achieving a higher pathological complete remission rate of mediastinal disease. Special precaution should be given with its use in can‐ didates before a planned pneumonectomy due to the higher perioperative mortalities. When preoperative radiotherapy is considered, a dose higher than 45–54 Gy in 1.8–2 Gy per fraction

fractions is as effective as conventional radiotherapy in 2Gy per fraction.

**4.1. Nonsmall cell lung cancer**

30 Radiotherapy

with the hypofractionated regime.

modality treatment.

*4.1.2. Locally advanced stage III disease: curative treatment*

had not been shown to give addition survival benefit.

Early radiotherapy to thorax in patients with incurable disease but no or minimal symptoms had not been shown to improve symptom control, survival, or quality of life. Hence, pallia‐ tive thoracic radiotherapy can be deferred till symptoms emerged. Common indications are cough, hemoptysis, chest pain, and airway obstruction [9]. The optimal radiotherapy dose and fractionation schedule remained unclear. While there is no significant difference in symp‐ tom control with different dose schedules, a small survival improvement may be seen with higher dose radiotherapy.

For malignancy‐related superior vena cava obstruction, external beam radiotherapy is effec‐ tive in 60% patients with nonsmall cell lung cancers and 80% patients with small cell lung can‐ cers [10]. Chemotherapy is another treatment option for patients with chemosensitive tumors like lymphoma, germ cell tumors, or small cell tumors. Intravascular stent insertion may be considered for patients that require rapid relief of symptoms, those who fail to response or relapse after radiotherapy.

Palliative radiotherapy can also be given to distant metastatic sites (e.g., bone, skin). Single frac‐ tion radiotherapy is as effective as longer course radiotherapy in pain and local symptom control.

#### *4.1.4. Postoperative treatment*

Adjuvant postoperative radiotherapy (PORT) helps to improve local control in patients with high risk of local recurrence after surgery, including those with pathological N2 disease and incomplete resection either microscopically or macroscopically. A careful evaluation of gen‐ eral conditions and remaining lung reserves is required before the start of treatment. It is not routinely given to early stage I–II disease with clear resection due to the potential detrimental effect on overall survival from previous meta‐analyses that include trials using large radiation fields and nonconformal radiation techniques. However, its role with the use of modern radio‐ therapy machine and conformal radiotherapy are unclear and further research is warranted.
