In this retrospective cohort study, we compared dosimetric parameters, toxicity, and clinical outcomes between 3D-CRT and VMAT in breast cancer patients who received adjuvant radiotherapy with RNI. The results showed that VMAT provided better target coverage and decreased total lung V20 Gy, with a slight increase in lung V5 Gy. Patients treated with VMAT experienced less frequent grade 2 or higher acute radiation dermatitis.
Conventional 3D-CRT is commonly used for adjuvant breast radiotherapy with RNI, using the tangential chest wall or breast and supraclavicular fields. This technique requires matching the fields, resulting in inadequate dose coverage near the matched line. Previous studies have shown that inverse planned IMRT offers dosimetric benefits over 3D-CRT [20, 21]. IMRT provides better target coverage, dose homogeneity, and conformity while reducing high-dose volumes to organs at risk. Our study showed similar results, with VMAT demonstrating superior target coverage and decreased total lung V20 Gy compared to 3D-CRT.
Due to laterality differences, it was challenging to compare the dose volume of the heart and esophagus between left and right breast cancer treatments. To address this, we conducted another study comparing dosimetric parameters between 3D-CRT and VMAT for patients who received left-sided breast radiotherapy with RNI [24]. The results showed significantly lower total and ipsilateral lung V20 Gy for VMAT compared to 3D-CRT, as well as lower V40 Gy, V35 Gy, and V25 Gy of the heart and LAD (data not shown). These findings suggest that VMAT may be an effective treatment option for left breast cancer with lower lung and heart doses than 3D-CRT.
Although VMAT effectively reduces the high-dose volume of organs at risk, it increases the low doses received by the lung. However, this increase is small and not clinically significant, and there was a low frequency of grade 2 or higher radiation pneumonitis. The increased low-dose volume does raise concerns about the risk of second cancer. Our study found no difference in second malignancy between 3D-CRT and VMAT, but we cannot conclude that increased low-dose volume is safe due to the short follow-up duration. Previous studies have estimated that the risk of secondary cancer after VMAT is higher than with 3D-CRT [25, 26]. To minimize the low-dose wash, advanced VMAT techniques such as tangent-based volumetric modulated arc therapy (TVMAT) may be helpful. Yu et al. presented TVMAT for adjuvant radiotherapy, including RNI of left breast cancer, which successfully decreased low-dose parameters and contralateral organ parameters while maintaining therapeutic efficacy [27].
Previous randomized controlled trials have shown that IMRT can reduce skin and soft tissue toxicity due to improved dose homogeneity [19, 28]. A large prospective multicentre cohort study of patients receiving adjuvant whole breast irradiation without RNI also found that inverse-planned IMRT reduced acute toxicity, defined as moderate to severe pain or moist desquamation, compared to 3D-CRT [29]. A retrospective cohort study also showed that IMRT helped reduce radiation-induced dermatitis and lung toxicity [30]. Our study's results are consistent with these previous findings. Fewer patients treated with VMAT experienced grade 2 or greater acute radiation dermatitis. Unfortunately, we could not evaluate other adverse events such as cardiotoxicity and esophagitis, as patients were allocated to treatment based on cancer laterality. Esophagitis tends to be more common in the treatment of left-breast cancer due to the location of the esophagus. Future studies are needed to assess these adverse events and clarify the benefits of VMAT in terms of toxicity to the heart and
esophagus.
Before establishing our clinical protocol in March 2018, the decision to irradiate internal mammary nodes (IMNs) was made at the discretion of the treating physician. Physicians tended to prescribe IMNs irradiation to patients with left-breast cancer because VMAT could include IMNs with a minimum dose increase to organs at risk. Therefore, we performed multivariate analysis to consider the difference in IMNs irradiation between the two groups, recognizing that the results may be less reliable due to the small sample size and events. The results indicated that VMAT was associated with improved RFS and DRFS.
Our findings suggest that the highly conformal dose distribution of VMAT may effectively eliminate microscopic residual cancer cells. However, there are limited reports on the disease control and survival advantages of VMAT in adjuvant breast radiotherapy. Further research is necessary to determine whether VMAT provides survival benefits.
Our study has several strengths. The allocation of patients to each radiotherapy technique was unbiased as it was based on the laterality of the breast cancer. Moreover, this is the study to compare disease control and survival between 3D-CRT and VMAT. The results are based on a diverse patient population and real-world practice data. However, the study has limitations such as its retrospective design, small sample size, and short duration of follow-up. Additional long-term follow-up is required to evaluate prognosis.