Introduction
Lung cancer is the leading cause of cancer deaths in the United States and around the world. Reference Dela Cruz, Tanoue and Matthay1 Lung cancer causes more deaths in the United States almost every year than prostate, breast, colorectal and brain cancers combined. Reference Siegel, Miller and Jemal2 The American Cancer Society’s estimates that for lung cancer in the United States for 2020, there were about 228,820 new cases of lung cancer with 135,720 deaths. Reference Siegel, Miller and Jemal2 The rapid increase in the worldwide prevalence of lung cancer is attributed mostly to the increased use of cigarettes following World War I, though increases in environmental air pollution are suspected to have been a contributing factor as well.
About 85–90% of lung cancers are non-small-cell lung cancers (NSCLC) and 10–15% are small-cell lung carcinoma (SCLC). There are three main types of NSCLC: adeno carcinoma (AC), squamous cell carcinoma (SCC) and large-cell carcinoma (LCC). AC is the most common form of lung cancer found in the outer region of the lung. SCC is found centrally in the lung, where the larger bronchi joins the trachea to the lung, or in one of the main airway branches and is generally linked to smoking. LCC grows and spreads quickly and can be found anywhere in the lung.
It was shown that surgically un-resected NSCLC receiving radiotherapy, after induction chemotherapy, provided a statistically significant survival advantage. Reference Sause, Scott and Taylor3 The role of radiotherapy in combined modality treatment of locally advanced NSCLC was shown to have significant long-term survival advantages. Reference Kubota, Furuse and Kawahara4 Addition of radiotherapy to chemotherapy produced local control and survival advantage. Reference Pignon, Arriagada, Ihde, Johnson, Perry and Souhami5 Better survival was shown using multi-field conformal therapy without increased toxicity. Reference Pignon, Arriagada, Ihde, Johnson, Perry and Souhami5 Due to the proximity of lungs to oesophagus, heart and spinal cord, optimal dose delivery to target volume within thorax is challenging.
For radiotherapy treatment, patients need to be immobilised during the simulation as well as treatment delivery. Computed tomography (CT) simulations providing image sets (slice by slice) are usually used as patient data for treatment planning system (TPS) and dose calculations. PET-CT improves the outline of the gross tumour volume (GTV). Once patient data are acquired, the images are imported in DICOM format for the generation of treatment plan. Different anatomical structures or regions of interest (ROIs) are defined and delineated so that different tissue volume can be identified by the TPS and proceed with the appropriate planning procedures. Planning target volume (PTV) that covers clinical target volume (CTV) with a margin of about 2–2.5 cm due to respiratory tumour motion and setup is defined and delineated as a target structure of interest. Heart, breast, oesophagus and spinal cord are the main organs at risk (OAR) for NSCLC treatment. For 3D conformal therapy (3D-CRT) planning techniques, parallel-opposed fields, three fields or two-field wedge pairs, as well as multi-fields are used to cover the size of PTV. Reference Bahri, Flickinger and Kalend6 MV beams are usually used and conformal treatment blocks are created in the beam’s eye view around the CTV with 2.5 cm margin. Reference Das, Cheng, Anderson and Movsas7
Intensity-modulated radiation therapy (IMRT) was first implemented in the early 1990s with the introduction of the first commercial IMRT delivery unit NOMOS Peacock system (NOMOS Corporation, Sewickley, Pennsylvania, USA), Reference Woo, Sanders and Grant8 when computing capability required for complex inverse treatment planning algorithms became available commercially. The unique feature of IMRT is that the leaves are known as multileaf collimators (MLCs) that help create the complex shape of the beam to conform radiation to the shape of the tumour while minimising exposure of surrounding critical structures. IMRT technology has the ability to treat patients with several different modes that include the complex volumetric-modulated arc therapy (VMAT) mode, when the gantry of the linear accelerator rotates at a constant or variable speed around the patient for a partial or full arc, MLCs are in constant motion and dose rate is continuously varied. Reference Herman, Schnell and Young9
IMRT can be an effective treatment modality for managing advanced-stage NSCLC and SCLC. Target delineation and organ motion due to respiration need to be carefully considered during the simulation. Respiratory motion has a significant impact on the accuracy of tumour targeting with radiation and is of particular interest in the treatment of NSCLC and other thoracic malignancies. With the image-guided radiation therapy (IGRT) technology, 4D-CT treatment planning may be used for radiation dose escalation with tighter radiation fields and has the potential for improving outcomes in patients with thoracic malignancies. Reference Vlachaki, Castellon, Leite, Perkins and Ahmad10 Irradiation to uninvolved lung and normal tissues need to be minimised by beam angle selections during planning. In addition to ROIs that are needed to 3D-CRT, IMRT needs inverse planning with fluence optimisation, MLC sequences, beam configuration, plan evaluations, etc. Reference Malisan11
IMRT plans are usually oriented up to nine beam angles and a low dose ‘bath’ of radiation is created outside the PTV. This effect (not spread out widely) also occurs in 3D-CRT where only two–four beam angles are usually used. Complex shapes of radiation with IMRT sometimes result in unwanted ‘hot spots’ or ‘cold spots’. Hotspots in OAR put patients at higher risk and cold spots within the PTV under-dose the tumour. IMRT is a technique where hundreds of small radiation beams with different intensities are delivered to provide precise tumour dose while minimising adjacent normal tissue doses and generate a conformal dose distribution with steep dose fall off at the boundary between tumour and normal structures. The aim of this brief literature review is to evaluate, which is the superior radiotherapy technique among 3D-CRT, IMRT and VMAT for the treatment of lung cancer.
Methods
IMRT usually consists of several treatment fields with different directions, hundreds of beamlets with modulated intensity, an advantage over 3D-CRT, whereas VMAT has an advantage over IMRT due to rotating beam utilisation. A literature search was conducted using PubMed/MEDLINE, BMC—part of Springer Nature, Google Scholar and iMEDPub Ltd with the following keywords for filtering: 3D-CRT, IMRT, VMAT, lung cancer, local control and radiobiology. Fourteen publications were selected for the comparison of 3D-CRT, IMRT and VMAT to determine which technique is superior or inferior among these three.
Results
After reviewing different journals and publications, Reference Giraud, Antoine and Larrouy14 papers were found and reviewed, outcomes of those works are shown in Table 1.
Table 1. Advantages and disadvantages of 3D-CRT, IMRT and VMAT for NSCLC
Discussion
For patients with locally advanced NSCLC treated with concurrent chemotherapy, IMRT had lower rates of severe pneumonitis than that with 3D-CRT. Reference Chun, Hu and Choy15 This finding supported routine use of IMRT for the treatment of lung cancer. IMRT showed comparable or better OS compared to 3-D CRT in patients with stage III NSCLC. Reference Kong and Hong17 Also, Harris et al. in a population-based comparative effectiveness study showed that IMRT had similar OS, cancer-specific survival and toxicity risks compared to 3D-CRT. Reference Harris, Murphy, Hanlon, Le, Loo and Diehn19 No adequate data were available to determine if IMRT was superior to 3D-CRT in the treatment of NSCLC when similar OS was observed. Reference Hu, He, Wen, Feng, Fu, Liu and Pu23 However, it was shown that IMRT reduced the incidence of grade 2 radiation pneumonitis with increased grade 3 oesophagitis. Reference Hu, He, Wen, Feng, Fu, Liu and Pu23 Both IMRT and 3D-CRT produced comparable pathological and clinical outcomes in another study. Reference Appel, Bar and Ben-Nun25
IMRT delivered a higher dose to the target and spared more critical organs than 3D-CRT. Reference Chang16 However, the utilisation of motion management with 4D-CT-based treatment planning system was crucial for superior IMRT performance. Planning process and treatment delivery with IMRT was time-consuming and placed a strain on valuable resources compared to 3D-CRT. Reference Chan, Lang, Rowbottom, Guckenberger and Faivre-Finn18 IMRT improved conformity and provided a possibility for dose escalation to tumour, minimising dose to OAR compared to 3D-CRT. Reference Yegya-Raman, Zou, Nie, Malhotra and Jabbour22 IMRT had somewhat better outcomes and because of its good toxicity profiles decreased the probability of developing late side effects or secondary malignancies compared to 3D-CRT. In some patient cases, 3D-CRT technique had an acceptable short-term effectiveness with a mild toxic reaction and improvement of clinical symptoms. IMRT, thus, can be an effective treatment modality and perhaps somewhat superior to 3D-CRT for treating advanced-stage NSCLC.
VMAT provides more conformal radiotherapy with dose escalation to high-risk areas of the tumour and spares more critical structures compare to 3D-CRT. The quality of patient life improved for both IMRT and VMAT with the minimisation of treatment-related toxicities such as pneumonitis and oesophagitis compare to 3D-CRT. Reference Chang16 With appropriate motion management and plan optimisation, IMRT and VMAT can provide more conformal radiotherapy, achieve better target dose conformity, can spare more critical structures and achieve lower treatment toxicity than 3D-CRT. IGRT and adaptive planning can be useful for minimising target miss and the risk of overdosing critical structures. VMAT requires less number of MUs and shorter treatment delivery time when compared to IMRT. VMAT showed high local control rates and low risk of normal tissue complication in a study by Yamashita et al. Reference Yamashita, Haga and Takahashi20 Heart dose was reduced in VMAT compared to IMRT. VMAT had superior delivery efficiency, better optimised plan quality for DVH and conformity. VMAT was, thus, recommended as a preferred modality for treating NSCLC compared to IMRT Reference Choi24 and of course 3D-CRT.
Conclusions
At present, most of the lung cancer patients are treated with IMRT and some with 3D-CRT. The use of VMAT to treating lung cancer is very promising; however, it is quite apparent that VMAT, whether superior or not, would need to perform a lot of clinical trials for NSCLC cases. It also ensures to provide low doses to the surrounding organs. Irrespective of which technique (3D-CRT, IMRT, VMAT) one uses, a high-precision TPS will improve TCP and also the quality of life of patients undergoing radiotherapy.
Acknowledgements
None.
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