The main question addressed in our study is whether IFRT IMRT is a suitable technique for the treatment of supra-diaphragmatic early stage HL patients and if it can replace IFRT 3DCRT. In our study the PTV coverage obtained with IMRT was significantly better compared with 3D-CRT and it depends on IMRT ability to modulate the intensity of each radiation beam that resulting on a high conformal delivery of total dose radiation to PTV. Our results were similar to those reported by other authors, who showed that IMRT treatment was superior to 3DCRT plans regarding the PTV coverage [13–17]. This physical and dosimetric concept can be translated in a maximization of the actual total delivered dose to the target volume and therefore with an increased probability of local control.
The open question is whether IMRT might lead to a lower dose to the surrounding organs and whether the rate of late complication could be reduced with IMRT, in particular lung toxicity and cardiac toxicity. In our study, IMRT showed an advantage respect to the 3D-CRT technique for the oesophagus and spinal cord. This dose reduction could translate in a less acute and late morbidity. In particular, the NTCP, V20 and maximum dose for spinal cord is significantly lower for IMRT than for 3D treatment in every patient. In case of mediastinal relapse, it could be important to reduce the total dose delivered to the spinal cord for eventual re-irradiation. About thyroid, in our study the dose parameters analysis showed that IMRT is no advantageous respect to 3D-CRT. When supraclavear and/or neck lymph nodes were included in the treatment volume, the multi-fields IMRT arrangement was not able to spare the thyroid glands. On the contrary, when a 3D-CRT (Antero-Posterior and Postero-Anterior in particular) was employed, the most part of thyroid gland was not included in the treatment fields. The mean actual dose delivered with 3DCRT to thyroid gland in our patients was 15.25 Gy, statistically lower than the 21.4 Gy with IMRT. When we considered the volumetric parameter V10, we showed also a statistically significant advantage for 3D-CRT respect to IMRT technique. No difference was recorded respect to NTCP parameters. Compared with the general population, long-term survivors of Hodgkin’s lymphoma have a higher incidence of thyroid abnormalities, including hypothyroidism, hyperthyroidism and thyroid neoplasms . Thyroid cancer is the second most common tumor reported among HL survivor patients. The Late Effect Study Group reported a 36-fold increased risk of thyroid cancer, with 95% of these cancers developing within the radiation field . In 461 paediatric HL patients, the 20-year estimated cumulative incidence of hypothyroidism stratified for radiation dose was 30% in patients who received 21 Gy or less and 61% in patients who received more than 21 Gy . Thus, it is reasonable that lowering the radiation dose to thyroid gland could reduce the risk of late toxicity as hypothyroidism and second cancer. We reported no difference between 3DCRT and IMRT regarding the coronary arteries and heart dose parameters evaluation, as well as for the NTCP. Although no difference in the mean dose was reported by Girinsky et al., they showed a reduction of V30 with IMRT plan. Other authors stated that the aim of heart sparing was best achieved with IMRT although complete elimination of high dose to some parts of the heart was not possible with any technique [13, 14, 18]. Therefore, moving from conventional radiation techniques to IMRT would reduce the risk of cardiac morbidity and mortality but the individual magnitude of clinical benefit is hard to predict. Moreover the patient anatomy, comorbidity and pre-existent hearth damage could be important adjunctive risk factors. One of the objectives of using IMRT for patients with HL is to reduce the radiation dose to the surrounding lung. No agreement was reached regarding a correlation between lung toxicity and IMRT in HD patients. Although a reduction of the mean dose to the lung with IMRT plans was reported, on the other hand an increase of V20 using IMRT planning was recorded in other papers [13, 14, 17]. We showed a reduction of V30 and of NTCP value using IMRT that reach a statistical significance while the V5 parameter was increased with IMRT. The relationship between this dose-volume constraint and the risk of lung toxicity has not been clearly defined. Moreover, whether low dose to a large volume is more important than higher dose to a smaller volume in the development of pneumonitis is unknown. In this context, the role of IMRT in supra-diaphragmatic HL patients remains largely unknown owing the concern that IMRT may deliver a low, yet damaging dose to normal lung tissue.
Finally, literature data seem uniformly believe that IMRT technique increases the dose delivered to the breasts in female patients with HL [13–15, 31]. Also in our experience, the 3D-CRT offers a more convenient dose distribution to the breast, in particular to the left breast, respect to IMRT. The impact of the low dose radiation in a large treated volume of the breasts related to the IMRT technique should be investigated in a prospective setting [15, 31]. The late occurrence of second breast cancer in HL survivors is a topic of paramount importance. In this cohort of patients cumulative absolute risks of breast cancer after 10, 20 and 30 years after the radiation treatment were 1.4%, 11.1% and 29.0%, respectively . Dosimetric studies showed IMRT as superior to 3D-CRT in terms of target coverage, conformity, and sparing of normal tissue but concerns has been raised about its carcinogenic risk [31–34]. It has been estimated that IMRT may increase the risk of second cancer by a factor of 1.2-8 but we must point out that now we have only dosimetric studies and no clinical data, given the short follow-up of patients treated with IMRT so far [28–30]. Other issues that should be considered are the time and resources required for IMRT planning. In fact we acknowledge that IMRT is quite a time consuming and labor-intensive procedure if compared to 3D-CRT (increased time for planning, delineation, dose delivery and quality assurance).
In our opinion, IMRT can be used in patients with HL supra-diaphragmatic, showing itself to be superior to 3D-CRT in terms of dose distribution within the target and reduction of dose to organs at risk, especially lung and bone marrow. It is worth noting that in the present study the number of fields used in 3D-CRT planning were sometimes different. However we believe that this could have a minimum impact on the target coverage (since similar average doses were obtained), even if it might play a role on the dose delivered to the OARs. Regarding the dose delivered to thyroid with IMRT technique, the decision should be made on a case by case basis. We point out also that in the absence of clinical data, IMRT should be used with caution in HL women patients. In conclusion, IMRT is a seducing treatment option in patients with early stage HL, but a number of theoretical and practical hurdles remain to be resolved before it can be used routinely in clinical daily practice