The traditional treatment of MF usually uses TSEI[3], the dual-frame six-field irradiation technology developed by the Stanford University School of Medicine was widely used[4], but there are many disadvantages, such as poor dose distribution and homogeneity, poor comfort and setup reproducibility, long treatment time, etc.[4]. HT can achieve ultra-long target treatment (160cm × 40cm) and dose-printing distribution, which is very suitable for the long and complex targets, such as total body multiple metastatic irradiations, craniospinal irradiation, total body irradiation, total marrow irradiation, etc.[6]. Hsieh CH et al.[7] first used HT to achieve TSHT; Schaff EM et al.[17] and Sarfehnia A et al.[22]also used HT to perform total skin irradiation, these studies showed the advantages of TSHT.
So far there is no report about TSHT of MF using total skin bolus by 3D printing technology. Based on our previous experience with TSHT where six patients using diving suits had been treated before, we studied the patient during the whole process of TSHT treatment[14]. A customized 3D printed TPU suit was used as a bolus, which solved the problem of insufficient skin dose deposition. It achieved uniform dose distribution, good fitness, a simple implementation process, good treatment effect, and low toxicity effects, it will provide one more treatment method and better clinical effects for the treatment of MF.
In this work, a 5mm TPU suit by 3D printing was used as a bolus to increase the skin dose. Hsieh CH et al.[7]used a 3mm diving suit as a bolus to make 90% of the target reach the prescribed dose. Schaff EM et al.[17] investigated two patients with MF to confirm that TSHT can substitute traditional TSEI using a 3mm diving suit as a bolus, the film verification proved that a diving suit can significantly increase the skin dose. Deveau MA et al.[8] treated a dog with cutaneous epitheliotropic lymphoma and 3D printing technology was used to produce a 10mm thick 3D mold scaffold with a density of 1.09g/cm− 3, achieving 92% of the target to reach the prescription dose. Baltz GC et al.[9] used 3D printing technology to produce whole scalp bolus to achieve total scalp irradiation treatment. So far there is no report about TSHT of MF using total skin bolus by 3D printing technology.
The prescription dose is 24 Gy in 24 fractions, and 5 times per week. The field width, the modulation, the pitch, and the dose grid are 5cm, 3, 0.287, and 0.195cm × 0.195cm, respectively. The key factor is the complete block with the distance to PTV that has a significant influence on the plan quality, this patient used a 4cm distance consistent with the results of previous studies[14].
Compared with the lower target, the dose distribution of the upper target is slightly worse, and the CI and HI index are consistent, the main reason is that the left and right arms make the lateral width greater than 40 cm, causing blind areas in certain angles unable to be irradiated. Sarfehnia A et al.[22] also had an overdose or underdose for the left and right arm during the TSHT of a child. How to deal with the right and left arm doses needs further research.
The most radiation toxicity is bone marrow suppression in the previous literature research. Schaff EM et al.[17]used TSHT in 12 Gy with 8 fractions, the mean dose of total bone marrow was controlled to 1.66 Gy, and finally grade Ⅳ bone marrow suppression occurred. Hsieh CH et al.[7] had similar bone marrow suppression rates used TSHT at a higher prescribed dose of 30 Gy. Why the patients experienced severe bone marrow suppression with such a low bone marrow dose, one explanation is that the TPS may not accurately simulate the actual bone marrow dose, another explanation is that the plan parameter with the mean bone marrow dose less than 2 Gy is not strict or predictable for the TSHT. To avoid the toxicity, total bone marrow was outlined one by one, such as bone_leg, bone_H&N, bone_pelvic, bone_spinal, bone_rib, bone_arm, bone_femer, strict dose limitations for bone marrow in plan design to reduce dose. The bone marrow dose has obvious differences as the closer distance to the skin. The bone_H&N, bone_femer, etc. are farther from the skin than bone_pelvis, bone_spinal, etc., so they relatively received slightly lower dose. Whether to reduce the bone marrow dose to lose part of the target or to increase the bone marrow dose to ensure the target prescribed dose needs to be determined by the physician based on the patient's situation. Although the 3D printed TPU suit as a bolus can increase the skin dose deposition, the patient is thin and part of the bone marrow is close to the skin, it was difficult to reduce enough conditions, which caused Ⅲ degree bone marrow suppression occurred when the patient was irradiated to the 12th, and the treatment was terminated.
MF is usually highly radiosensitive. Radiotherapy plays a major role in the treatment of MF and is also one of the recommended treatment methods[23]. The prescribed dose can be selected from a wide range according to the purpose of the treatment, normally 15–20 Gy is sufficient for palliative treatment, but recent studies showed that the complete remission rate is only 55% for 10–20 Gy, when the dose reaches 30 Gy or more, the complete remission rate can reach 94%, the dose of a single course of treatment should generally not exceed 36 Gy, otherwise, the acute phase response will be severe[2]. The recommended prescription dose of cutaneous lymphoma from the European Organization for Research and Treatment of Cancer (EORTC) consensus is 30-36Gy during 6–10 weeks, and should be reached at least 26 Gy in a cone-shaped skin at a depth of 4 mm along the central axis[23]. However, the low-dose model has been gradually promoted in recent years, and the main feature is the shorter treatment time and the lower toxicity effects. The prescribed dose selected in this study is 24 Gy with 24 fractions, 5 times per week. The choices of different research institutes are not completely consistent. Hsieh CH et al.[7] used a 30 Gy with 40 fractions. Schaff EM et al.[17] used a 12 Gy with 8 fractions; Haraldsson A et al.[21] used a 32 Gy with 24 fractions. Therefore, different institutes need to choose an appropriate prescription dose and the number of fractions according to the actual situation of the patient.
The measured dose was not much different from the calculated dose, which is consistent with the results by Akbas U et al.[25]. The D2 and D4 deviations were more than 3% due to bolus fit and involuntary movements, but both were less than 5%. B4, C3 and D3 deviations are lower because of the fit of the bolus and involuntary slight movement. For the B3, B5, C2, C4, D2 and D4 on the left and right arms, since the degree of freedom of the arm was larger than the body and the repeatability was poor, resulting in the regional deviation as slightly larger the total body from the shoulder to the palm, but they were all within 3%. On the hand, the deviation was due to segmented treatment, the measured films received the scattered rays during the treatment of other segments. On the other hand, the inaccurate calculation of the surface dose by the planning system may also cause the dose deviation[26], measured films also receive the extra dose by MVCT, which was also a factor that the deviation to be slightly higher. In general, most of the results were within 3%, and even the regional deviation of excessive motion range was within 5%, which ensured the accuracy of the delivered dose.
The beam-on time of the upper target was 1519.3 s, the beam-on time of the lower target was 637.7 s, and the total beam-on time was 2157 s (Table 6), which was about 25.3 min. The customized TPU suit is not as convenient as a conventional diving suit, which need to be worn in the treatment room and requires an additional half hour. The preparation time, the setup time and the MVCT image guide were added up to one and a half hours. Compared with the two and a half hours of TSEI, the time has been shortened by nearly half[27], which has significantly improved the treatment efficiency. The patient was more comfortable and maintains the repeatability of the position well in the supine position than in the traditional standing treatment. At the same time, the intensity-modulated treatment plan has greatly improved the HI and CI, thus ensuring the accuracy and safety of the treatment.
The deviation for TSEI between the measured dose and calculated dose can reach up to 40%, such as the perineum and eyelids can be as high as 90%[25]. In addition, the depth of skin tumors was usually more than 4 mm, so there was an insufficient dose by TSEI. HT has advantages in long target, which provides uniform dose, precise dose depth control and low organ toxicity[26] and TSHT can be used instead of TSEI. In this case, the upper and lower target reached 95% of the prescribed dose, and the maximum dose was 115%. The dose deviation was much smaller than TSEI. At the same time, the complete block was 4 cm away from PTV significantly reducing the internal OARs dose, which greatly decreased the incidence of toxicity.