In the era of IMRT, the advantages of ART in ensuring adequate dose for target volumes and safe dose for essential normal structures have led to its widespread use in the treatment of NPC 17. Previous studies focused on the benefits of adaptive replanning in treatment of NPC which included increase LRFS rate, alleviate side effects, and improve QoL10,11,15,18. Moreover, information on contouring the target volumes of replanning for optimizing the early response during IMRT in NPC is limited. No conclusions have yet been reached on how to describe the target volumes and the appropriate radiation dose of adaptive replanning. The current study demonstrates the practicability of adapting the target volumes in the medium term of IMRT and reduce the radiation dose for tumor shrunken area depending on extrapolations from available data on locoregional recurrences, and presents our experiences regarding the description of target volumes for adaptive replanning and the optimal dose for tumor shrunken area in NPC.
Owing to the fundamental principles of radiobiology19, only a large tumor burden necessitates a higher radiation dose for effective treatment. Previous research had shown a radiation dose of 50 Gy was effective for controlling over 90% of subclinical diseases, 60 Gy for controlling microscopic diseases, and a higher dose for treating clinically identifiable diseases in NPC20. However, for the primary tumor and nodal mass shrunk to subclinical lesions during IMRT, dosing with the same amount of radiation as the primary tumor seems unreasonable. Consequently, we hypothesized that the residual diseases that could be seen by CT or MRI during IMRT still had a significant tumor burden and must be distinguished as GTVs obtaining the adequate radiation dose. Regarding tumor shrinkage in which there was a dramatic drop in tumor cell count and undetectable by CT or MRI, the disease might be delineated into the high-risk region getting a relatively lower dose, such as 60Gy. This therapeutic strategy could not only be conducive to give the adequate dose to the residual disease and tumor shrunken area during IMRT, it is also necessary to further decrease the high-dose region of organs at risk, especially for those who had large tumor closed to or even overlapped critical normal structures. Similar approaches were used to describe the target volumes and appropriate dose for tumor shrinkage following induction chemotherapy in NPC patients21–24.
There is limited study concerning on the description of target volumes and appropriate dose for tumor shrunken area in patients with NPC receiving adaptive replanning during IMRT. Hansen et al. maintained the size of the initial GTVs when recontoured the GTVs for replanning25. Zhao et al. recontoured GTVs based to the shrinkage and deformation of the primary tumor and lymph nodes shown by re-simulated CT imaging, while maintaining the size of the initial CTVs. Excellent local-regional control was established in their research group, with a 3-year local relapse-free survival rate of 72.71% for patients receiving replanning. Additionally, the radiotherapy related acute and late toxicities were alleviated10. However, the failure patterns especially for locoregional recurrences were not analyzed, which was relatively important for evaluating the feasibility of this specific strategy. Xie et al. conducted a study based on 54 NPC patients receiving IMRT with adaptive replanning. They defined replanning GTVs as all residual diseases, replanning CTV1 as the same as the initial CTV1, and replanning CTV2 was not delineated. Over 65 Gy was administered to the tumor regression area, and a total of 45–47 Gy was given for CTV2 over the course of 25–26 fractions. After a median follow-up time of 30 months, four patients developed locoregional recurrence with none occurring in the area of regression or CTV2 area26.
In the present study, 274 participants with non-metastatic NPC who had IMRT with and without replanning were evaluated. Tumor regression area was included in replanning CTV1 instead of replanning GTVs, and the prescribed dose for this area was 60–66 Gy. Consistent with previous reported10,11,15, IMRT with replanning could significantly improve the local regional control for NPC patients. Among 100 patients without replanning, 19 patients had locoregional recurrences, 16 (84.2%) were considered as in-field failure, 2 (10.5%) were considered as marginal failure, and 1 (5.3%) was out-field failure. Among 174 patients with replanning, 15 patients had 17 locoregional recurrences, 16 (94.1%) were considered as in-field failure, and 1 (5.9%) was out-field failure. No marginal recurrence was observed in patients with replanning, which means that reducing the GTVs and the radiation dose prescribed for tumor shrunken area does not produce additional locoregional recurrence in this area. Our finding indicated that adapting the target volumes and altering the radiation dose prescribed to the area of tumor reduction were achievable. It should be noted that in the current research, for the bony structures of skull base invasion, the target volumes were described depending on the initial images despite tumor regression during the course of IMRT.
There is a main limitation that should be addressed in our study. Although all of the patients in the current cohort had popular treatment modalities at that time, the treatment modalities were not completely identical along the time frame especially for the systemic treatment strategies. Most of the patients in this study received adjuvant chemotherapy instead of induction chemotherapy. Since the patients receiving induction chemotherapy might have limited response to 1st IMRT fractions, the percentage change in volume for replanning PGTV in comparison to baseline PGTV might be small. Thus, the findings need to be explicated thoroughly and confirmed by elaborately conducted investigations in the future.