Background

Post-mastectomy radiation therapy (PMRT) is technically difficult, given the complexity of the target volume and its proximity to critical structures, including the heart, lung, brachial plexus, and contralateral breast [1,2,3]. More advanced techniques, such as intensity modulated radiation therapy or volumetric modulated arc therapy (VMAT) can achieve highly conformal dose distributions with improved target volume coverage and sparing of normal tissues compared to conventional techniques [4]. These techniques have the potential to improve treatment outcomes for PMRT and significantly reduce the dose to the heart and the ipsilateral lung [5,6,7,8]. Nevertheless, uncertainties related to inter-fraction positioning may lead to inaccuracies in the dose delivered [9]; the steepness of the dose-effect curves can limit the efficacy of VMAT, thus affecting patient outcomes for both local tumor control and normal tissue complications. The radiation dose delivered to the heart should be monitored as even lower doses of radiation to the heart may lead to a relevant injury [10, 11]. As previously reported [12,

Results

Table 1 presents the dosimetric parameters of the reference treatment plans approved and clinically delivered for the 11 cases studied. Tables 2 and 3 presents respectively, the mean absolute differences and the standard deviation of the targets and OARs DVH dosimetric parameters obtained between the perturbed and the corresponding reference plans for each isocenter shift. The absolute differences were given for the dosimetric parameters obtained with the perturbed plan minus those obtained with the reference plan.

Table 1 Dosimetry of the reference plans for the cases studied
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Table 2 Mean absolute difference and standard deviation of the CTVs DVH dosimetric parameters in the 11 cases studied
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Table 3 Mean absolute difference and standard deviation of the OARs DVH dosimetric parameters in the 11 cases studied
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Significant absolute percentage differences were registered for isocenter shifts of 10 mm with a mean decrease for CTVth ∆ D95, ∆ D98, and ∆ Dm of 14.4% (range 3.4–27.1), 19.1% (range 4.5–35.7), and 3.7% (range 1.5–6.2), respectively; while for CTVsv ∆ D95, ∆ D98, and ∆ Dm mean decreases of 11.2% (range 5.0–22.1), 16.9% (range 9.1–30.2), and 2.1% (range 1.5–2.7), respectively, were registered. The maximum dose for both targets was only slightly affected and only for the anterior and right directions with a maximum increase of 1.7 Gy. For 5 mm isocenter shifts, ∆ D95, ∆ D98, and ∆ Dm decreased to 3.8% (range 1.8–7.6), 6.1% (range 3.0–11.6), and 0.6% (range 0.0–1.2), respectively, for CTVth and to 2.6% (range 1.4–4.8), 4.4% (range 1.4–10.7), and 1.2% (range 0.8–1.4), respectively, for CTVsv. For 3 mm isocenter shifts, lower mean differences were found: ∆ D95, ∆ D98, and ∆ Dm decreased to 1.2% (range 0.2–2.8), 2.0% (range 0.6–5.6), and 0.4% (range 0.0–0.8), respectively, for CTVth, and to 0.8% (range 0.2–1.4), 1.4% (range 1.0–2.8), and 0.8% (range 0.6–1.0), respectively, for CTVsv.

For the OARs, only isocenter shifts in the right, posterior, and inferior directions worsen the plan dosimetry; particularly, for the left lung means ∆ V20, ∆ V40, and ∆ Dm of + 8.4%, 7.8% and 3.6 Gy, + 3.9%, 3.8%, and 1.7 Gy, and + 2.3%, + 2.1%, and + 1.1 Gy, were registered for 10, 5, 3 mm isocenter shifts. For the heart, the higher difference was registered for isocenter shifts in the posterior direction with mean ∆ V25 and ∆ Dm of + 7.0%, and 3.0 Gy, of + 3.0%, and + 1.4 Gy, and of + 1.6% and + 0.8 Gy, respectively, for 10, 5, 3 mm isocenter shifts.

Discussion

In this study, the impact of positioning errors on the plan dosimetry of a VMAT PMRT was investigated for three different magnitudes and six different directions of isocenter shifts. The results obtained make it possible to share some considerations. As expected, the impact on the plan dosimetry resulting from a misalignment of the isocenter increases with the magnitude of the isocenter shift, generally for both targets and OARs; nevertheless, shifts of 3 mm that slightly affect the target coverage could be relevant for the increase of dose of the OARs as shows Fig. 1 for a representative patient; the heart, lung, and CTVth DVHs were portrayed for 10, 5, and 3 mm isocenter shifts.

Fig. 1
figure 1

DVHs of the reference and perturbed plans for a representative patient. The DVH of the plans perturbed by isocenter shifts of 10, 5, 3 mm were reported in panel a, b, c, respectively

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The directions that most affect the coverage of both targets (highlighted in bold in Table 2) are the anterior and left directions. This is understandable because the proximity of the heart and lung to the target in the posterior direction quickly decreases in respect to the target’s coverage when the isocenter shift is in the opposite direction. This is due to the strong dose gradient that must be present between target and heart to ensure an accurate dose coverage of the first without affecting the second; the dose gradient is highly accentuated in cases of modulated intensity treatments. The same applies to the left direction, because the lateral gradient must be steep to avoid as much as possible a dose to the contralateral breast. Isocenter perturbations in the inferior and superior directions have lower impacts on the dose coverage of the CTVth and CTVsv, respectively, because both targets are contiguous, while the opposite directions superior for CTVth and inferior for CTVsv lead to a non-negligible targets underdosage. We can also observe that 3 mm isocenter shifts only affect the dosage of the targets slightly, as expected, considering that the treatment plan was optimized on the PTV obtained with an isotropic expansion of 3 mm around the CTV. These results are aligned with other studies [22] whose authors have found that shifts in the position of the isocenter as large as 3 mm tend to have a modest impact on the quality of VMAT plans.

The dosimetric disagreement of the OARs must be analyzed closely and at the same time as that of the targets. If, in fact, some directions (superior, left, and anterior) do not affect the organs at risk as they move them away from the treatment field, other directions (inferior, posterior, and right) that only slightly affect the variation in target coverage lead to nonnegligible overdoses of the organs at risk as they significantly increase the portion of the lung and heart irradiated. Moreover, isocenter misalignments of 3 mm, with a negligible impact on the target’s dose coverage, maintain positive lung absolute dose differences ∆ V20 and ∆ V40 greater than 1.9% and 1.6%, respectively, and heart ∆ V25 difference not negligible in the posterior direction of 1.6%. In Fig. 2 are portrayed the 50 Gy and 20 Gy isodose lines of the reference and perturbed plan for different isocenter shifts for a representative patient. For 3 mm shifts the 50 Gy isodose line well encompasses the CTVth, while the 20 Gy isodose line includes a larger portion of heart and lung compared with the reference plan.

Fig. 2
figure 2

CT transversal scan of a representative patient with isodoses lines of the reference and corresponding perturbed plan. CT transversal slice of a representative patient with 50 Gy, and 20 Gy isodose lines of the reference plan (Ref) and of the corresponding plan perturbed with isocenter shifts in the posterior direction of 10, 5, 3 mm (Post 10, Post 5, Post 3)

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The higher the dose of the incidental radiation to the heart, the higher the probability of an event of cardiovascular complication or generally cardiotoxic effects [23,24,25]; this dose effect relationship forces the radiation oncologist to take in account that isocenter misplacement of few millimetres, may have consequence on the OARs when the reference doses were already close to the threshold of acceptability.

The results of this study were obtained using the patient data derived from the clinical practice of our department. The research does not have the value of a multi-institutional quality- assurance program, therefore the results cannot be generalized. Nevertheless, the findings obtained show that OARs dose deviations from the initial treatment conditions can arise for isocenter misplacement that slightly affect the target coverage.

Knowledge of dose coverage variation in chest wall tissue, adjacent lung, and heart are necessary to properly manage the accuracy of the treatment delivered along the treatment course. Isocenter positioning variations can be seen where the online match had failed on an individual day, although the neighbouring fractions were well matched. The use of custom margins in specific “critical” directions, for OARs, combined with the margins already in use by PTV, would help to limit the impact of possible positioning errors that may occur when setup support technologies (CBCT, image guidance, etc.) are not available or cannot be scheduled on a daily basis. Investigations performed with own equipment can highlight the impact on the plan dosimetry of isocenter positioning variations in specific directions; asymmetrical action levels could be considered for the daily verification.

Conclusion

Inaccuracy in isocenter positioning for VMAT left-sided PMRT irradiation may impact the dosimetry of the CTVs and OARs to a different extent, depending on the directions and magnitude of the perturbation. The acquired information could be useful for planning strategies to guarantee the accuracy of the treatment delivered.