This article reports a crucial experience, justifying that radiotherapy of the LSBCP led to an early gastric reaction, such as nausea, vomit, and loss of weight. It is well established that radiotherapy-induced gastric reaction is usually associated with irradiation for upper abdomen tumours, such as pancreatic, gastric, or liver cancer [14]. Total body irradiation can also cause vomiting. As we mentioned earlier, RINV usually resulted from the irradiation of OARs in the upper abdomen as the peripheral trigger zone of emesis. Because of the deep abdominal location, the OARs are normally excluded from high radiation doses in breast radiotherapy. This is the reason why the RINV in breast cancer had been neglected for such a long time. For most patients, stomach dose can be significantly reduced if adequate blocking is used. But for the patients who have huge a stomach, the large volume of the stomach squeezes the organs around, including the left lung upward, leading to a relatively shorter distance between stomach and left breast. As a result, in our clinical practice, a considerable section of patients was found to endure grade I-II gastrointestinal toxicity ever since the hyper-fractionated radiotherapy plan was conducted in our centre. RINV usually occurred immediately or several hours after breast radiotherapy. At the end of radiation, some patients had weight loss more or less.

In our study, acute radiation-related gastric complications were associated with the irradiation dose of stomach. With a higher Dmax/F, D60cc/F, D30cc/F, or D10cc/F, the incidence of gastric complications grew significantly. As is shown in Fig. 1, most of the patients who suffered from gastric poisoning had a considerable portion of the stomach in the high-dose zone. A higher max dose or a more extensive high-dose zone in stomach is usually correlated with a larger stomach volume, as is depicted in Fig. 4. The dosimetric distribution in the stomach is quite different on account of varying stomach volumes. A larger stomach volume leads to the closer distance between the stomach wall and the chest wall, and then shortens the gap between the stomach and the PTV.

Numerous publications have investigated the dosimetric advantages in heart, LAD, lung, and liver for breast cancer radiotherapy in DIBH mode [17,18,19,20,21,22,23]. However, this is the first report that observed the stomach dose in DIBH and FB. Ever since the DIBH technique was applied in our centre, a considerable portion of LSBCP received radiotherapy in the new respiratory gating mode. There was a significant difference in the occurrence rate of gastric toxicity between the FB and DIBH groups. Variability in the stomach dose can be due to physiological factors: during DIBH, the lungs become enlarged and push the diaphragm downward, leading to a relatively long distance between stomach and PTV and lower radiation dose compared with FB. Therefore, in DIBH mode, advantageous dose distribution in the stomach can be achieved, resulting in a lower probability of gastric symptoms.

In addition, although there was no relationship between the gastric side effects and fractionated regimen in this study, fewer fractions always lead to higher PTV single dose irradiation. The prescription dose to PTV was 2.0 Gy ~ 2.22 Gy/F in the conventional fraction cohort, while in hypofraction mode the dose was 2.7 Gy ~ 3.33 Gy/F. Because of the short distance between left breast and stomach in certain situations, higher dose fractionated irradiation in PTV could result in more irradiation dose/F in the stomach. However, a considerable portion of the patients (40/50) was treated in hypofraction mode under the DIBH technique, the occurrence of gastric symptoms rate might be decreased because of the stomach movement.

As the application of the hypofractionated regimen becomes more widespread, more and more LSBCP might experience upper digestive tract side reactions. Poor appetite, nausea, and vomiting during radiotherapy could result in weight loss in patients, which will lead to changes in body shape. As a result, the safety and accuracy of treatment could be cut down, especially for the PTV located in body surfaces, such as in the breast and chest walls. In Mary Feng’s study focused on intrahepatic malignancies radiotherapy, gastric bleeds might occur after radiotherapy at a median time of 4 months [24]. In another study published in 2009, the risk of gastric cancer as a second malignant tumour rose with the increasing stomach mean dose (Dmean) [25]. Therefore, the gastric dose in left breast radiotherapy should be attached importance to.

Emami et al. [26] estimated doses with a 5% risk at 5 years (TD5/5) for late stomach toxicities in 1991. The TD5/5 estimated for severe gastric complications after the whole-stomach irradiation dose of 50 Gy, and 1/3 volume of the whole-organ irradiation dose of 60 Gy, had been widely accepted as a dose limit guideline. However, the dose limit was established in the era of three-dimensional conformal radiation therapy (3D-CRT). As new techniques, such as intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), tomotherapy, and even intensity-modulated proton therapy (IMPT) [27,28,29], had been widely implemented in breast cancer radiotherapy, new dose limitation of stomach should be recommended. There were no gastrointestinal symptom references to suggest a safe dose with the current radiotherapy techniques, a reduction to gastric symptoms should be conducted by proposing a new stomach dose limitation when the radiotherapy plan was formulated. Considering that most centres usually couldn’t scan the entire stomach in breast cancer simulation, we collected Dmax, D60cc, D30cc and D10cc as statistic variables. The current work demonstrated that Dmax/F, D60cc/F, D30cc/F and D10cc/F in stomach were associated with gastric side effects. So further study is required to validate a specific OAR limitation achievable for lower stomach side effects.

When appraising our products, both advantages and limitations should be taken into account in the meantime. Up to now, seldom evidence published in the literature demonstrated that radiotherapy of LSBCP is correlated with an increased risk of gastric reaction. In the current study, we showed an increased incidence rate in LSBCP received hyper-fractionated radiotherapy. What’s more, we suggested dose limitations that radiation oncologists can use to check their radiotherapy plan. Meanwhile, there are several limitations to the study. First, the stomach wall may change depending on the volume of the contents. Planned doses for 3D-CRT + IMRT cannot be flexibly modified or adjusted according to day-to-day or real-time organ displacements around the stomach, resulting in different digestive symptoms after everyday treatment. Second, seldom publications studied the stomach dose limitation as an OAR in breast cancer, so there weren’t enough applicable references. Third, gastroscopy was not conducted after radiotherapy to investigate acute radiation-related gastric toxicity. Moreover, real long-term side effects were not reported because of the short follow-up period.

In conclusion, a huge stomach could be closer to the breast PTV, so large meals should be avoided before treatment. DIBH treatment should be implemented in centres where conditions are satisfied to reduce radiotherapy side effects. Furthermore, dose limitation in stomach should be considered when the radiotherapy plan was formulated, especially for the patients treated with hypofractionated radiotherapy.

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