Abstract
Purpose
This study evaluates the hypothesis that a volumetric skin-sparing planning technique (SSPT) will reduce acute dermatitis in patients treated to the breast or chest wall (CW) with proton pencil-beam scanning (PBS).
Methods and Materials
In January 2022, our center incorporated volumetric-based skin-sparing objectives in addition to skin hot spot evaluation as an SSPT. The SSPT incorporated an objective to limit the volume of a skin evaluation structure (skin-eval) receiving 95% of the prescription dose or more (V95%Rx) to ideally < 50%. We compared target coverage, robustness, skin-eval dosimetry, and acute on-treatment skin toxicity in patients treated with and without incorporation of this SSPT. Patients with skin/dermal lymphatic invasion or inflammatory breast cancer were excluded.
Results
A total of 84 patients who received breast/CW PBS were included (43 planned without and 41 with the SSPT). There was no difference in percentages of patients treated with intact breast/CW/immediate CW reconstruction between groups. Mean skin-evalV95%Rx was 72% vs 30%, P < .0001, for those treated without versus with an SSPT. Maximum %Rx to the skin-eval volume of 0.03, 0.3, and 1 cc was higher in patients treated without versus with an SSPT (103.1% vs 101.5%; 101.3% vs 100.4%; and 101.8% vs 99.7% [all P ≤ .0001]), respectively. There was a small difference in the mean clinical target volume V97.5%Rx in patients treated without versus with the SSPT (97.8% vs 96.5%, P = .0003). Patients planned using the SSPT demonstrated reduced rates of grade 1 breast pain at week 2 (12% vs 33%, P = .0424) and grades 2 and 3 dermatitis at weeks 4 and 5 (week 4 dermatitis ≥ grade 2, 18% vs 43%, P = .0224; week 5 dermatitis ≥ grade 2, 45% vs 69%, P = .0006). There were numerically more patients requiring a treatment break or not completing the full intended prescription (4 vs 1) in the pre-SSPT cohort.
Conclusions
The use of an SSPT may reduce acute skin toxicity in patients with breast cancer treated with PBS.
Introduction
Breast cancer is the most common cancer diagnosed in women.1 For most breast cancer patients, adjuvant radiation therapy (RT) following breast-conserving surgery, or mastectomy in cases of higher-risk disease, improves local control and overall survival.2,3 Proton beam therapy (PBT) has seen rapid growth in breast cancer treatment, particularly when regional nodal irradiation is required, because of the expanded availability of PBT and increased recognition of the late effects of RT in survivors.3 Potential advantages of PBT for patients with breast cancer include reduced cardiopulmonary toxicity, improved arm, and shoulder functional outcomes, and a potentially decreased contralateral breast radiation exposure.4, 5, 6, 7
Although PBT poses advantages in the reduction of RT dose to nontarget critical tissues, early experience with PBT suggested higher than expected on-treatment skin toxicity rates with PBT plans to the breast or chest wall (CW) using passive scatter (grade 2, 75%8; grade 3, 43%9) and uniform scanning techniques (grade 2, 72%10).
More modern pencil-beam scanning (PBS) techniques permit modulation of the entrance dose, allowing skin-sparing. However, in a study from the University of Maryland quantifying acute skin toxicity in patients treated with PBS proton therapy versus photon RT, grade 2 or higher dermatitis was still more prevalent in patients receiving PBS-PBT compared with photon RT at 69% versus 30%, even with no differences in observed maximum dose, mean dose, and maximum dose to a 10 cc volume of the skin.11 A report from the Mayo Clinic of patients treated with PBS-PBT in the postmastectomy setting using the technique of limiting the maximum dose to a volume of 1 cc < 102% of the prescription resulted in similar rates of dermatitis in their proton cohort compared with the photon cohort.12 Further research is needed to optimize the planning and delivery of proton therapy to continue to mitigate the toxicity of treatments.
At our institution, breast and CW PBT is delivered using PBS with a minimum of 2 fields. Initially, skin dose evaluation focused on mitigating skin hot spots. To address concerns about acute skin toxicity with PBS-PBT, our institution introduced a novel volumetric skin-sparing planning technique (SSPT) for proton planning in breast and chest CW patients. This study evaluated SSPT dosimetry and hypothesized that it reduces acute dermatitis during PBS.
Materials and Methods
Patient selection
Consecutive patients receiving PBS for breast cancer treatment from the time of our center opening in March 2020 through January 2023 were reviewed. Patients with skin, dermal lymphatic involvement, or inflammatory breast cancers were excluded.
Treatment planning
Treatment planning was performed on Raystation version 10A and delivered using the Ion Beam Applications Proteus Plus proton therapy system. Our institutional standard plan for breast and CW PBS consists of 2 en-face fields with a hinge angle of at least 30 degrees and a 4 cm range shifter with a single field uniform dose technique. Uniformly, clinical targets were delineated by cropping off the skin surface by 3 mm for CW and 5 mm for intact breast; however, further skin-sparing strategies were initially limited to restricting hot spots on the 3 mm or 5 mm skin structure for CW or breast PBS plans, respectively. In January 2022, our center added volumetric-based skin-sparing objectives in addition to hot spot evaluation as an SSPT. To start, a consistent skin evaluation structure (skin-eval) was defined as the skin rind that existed only within 5 mm of the clinical target volume (CTV) and included a rind of 3 mm for CW and 5 mm for intact breast, bound by the patient's surface. The SSPT incorporated an objective to limit the volume of skin-eval receiving 95% of the prescription dose or more (V95%Rx) to ideally < 50% (goal < 60%) while still prioritizing CTV coverage and robustness, as shown in Fig. 1.
Figure 1.
Representative case of pencil-beam scanning (PBS) skin-sparing technique. Shown is a 5 mm skin evaluation structure (skin-eval, pink) structure created by defining a rind of 5 mm of skin within 5 mm of the clinical target volume (CTV). The 90% prescription isodose line (yellow) covers most of the skin but the 95% prescription isodose line (orange) covers < 50% of the skin-eval.
Skin toxicity
Skin toxicity was scored using the Common Terminology Criteria for Adverse Events version 4.0 criteria and the Radiation Therapy Oncology Group criteria reported by physicians on a weekly basis during weekly on-treatment visits. Within dermatitis scoring, the grade of erythema (1 = faint, 2 = moderate to brisk) and desquamation (1 = dry; 2 = moist, confined to skin folds/creases; 3 = moist, areas other than folds/creases) were separately reported, given the difference in management of these 2 subgroups of dermatitis. As is standard practice in our clinic, all patients were provided with the same skincare education sheet for guidance on the use of moisturizers, and silver sulfadiazine or silvasorb gel was recommended when grade 2 or greater desquamation was observed. Adherence to skincare recommendations was not prospectively tracked; however, it was encouraged on weekly on-treatment visits.
Statistical analysis
Data were analyzed using SAS software (version 9.4. SAS Ins). Fisher's Exact test and Wilcoxon rank-sum test were used to compare baseline demographic characteristics, target coverage, robustness, skin-eval dosimetry, and acute on-treatment skin toxicity in patients treated with and without incorporation of this SSPT. P values were not adjusted for multiple tests. P < .05 was deemed significant. All dosimetric analyses were limited to the initial treatment plan for consistent evaluation across patients. Boost plan dosimetry was not included in this analysis.
Results
Eighty-four consecutive patients treated at our institution with proton therapy met inclusion criteria for analysis, including 43 patients who were planned and treated without a volumetric SSPT and 41 patients who were planned and treated with a volumetric SSPT to attempt to better spare the skin surface and reduce risk of toxicity. The patient characteristics are shown in Table 1. There were no statistically significant differences in the collected patient and treatment characteristics between the 2 cohorts, apart from a higher percentage of patients treated without SSPT receiving moderately hypofractionated RT (14% vs 2%, P = .0459). There were no differences in patient race, smoking history, diabetes history, body mass index, connective tissue disease history, chemotherapy history, prior radiation overlap, radiation treatment site (breast, CW without reconstruction, or CW with reconstruction), and resulting skin rind structure for dose evaluation as well as receipt of boost across the 2 cohorts.
Table 1.
Patient characteristics overall and between groups of those treated without and with a skin-sparing planning technique
| Characteristics | Patients treated without volumetric skin-sparing (N = 43) |
Patients treated with volumetric skin-sparing (N = 41) |
Total (N = 84) |
P value |
|---|---|---|---|---|
| Race, n (%) | .1645* | |||
| White | 23 (53.5%) | 24 (58.5%) | 47 (56.0%) | |
| Black | 6 (14.0%) | 9 (22.0%) | 15 (17.9%) | |
| Hispanic | 8 (18.6%) | 2 (4.9%) | 10 (11.9%) | |
| Asian | 6 (14.0%) | 4 (9.8%) | 10 (11.9%) | |
| Other | 0 (0.0%) | 2 (4.9%) | 2 (2.4%) | |
| Smoking history, n (%) | .6371* | |||
| No | 29 (67.4%) | 30 (73.2%) | 59 (70.2%) | |
| Yes | 14 (32.6%) | 11 (26.8%) | 25 (29.8%) | |
| Diabetes, n (%) | 1.0000* | |||
| No | 37 (86.0%) | 35 (85.4%) | 72 (85.7%) | |
| Yes | 6 (14.0%) | 6 (14.6%) | 12 (14.3%) | |
| Connective tissue disorder, n (%) | 1.0000* | |||
| No | 42 (97.7%) | 41 (100.0%) | 83 (98.8%) | |
| Yes | 1 (2.3%) | 0 (0.0%) | 1 (1.2%) | |
| Body mass index (kg/m2), n (%) | .1402* | |||
| <18.5/underweight | 1 (2.3%) | 1 (2.4%) | 2 (2.4%) | |
| Normal (18.5-< 25); | 19 (44.2%) | 10 (24.4%) | 29 (34.5%) | |
| Overweight > 25-< 30 | 11 (25.6%) | 10 (24.4%) | 21 (25.0%) | |
| Obese > 30 | 12 (27.9%) | 20 (48.8%) | 32 (38.1%) | |
| Receipt of preradiation chemotherapy, n (%) | .0757* | |||
| None, or hormonal therapy only | 14 (32.6%) | 5 (12.2%) | 19 (22.6%) | |
| Neoadjuvant chemotherapy | 14 (32.6%) | 20 (48.8%) | 34 (40.5%) | |
| Adjuvant chemotherapy | 15 (34.9%) | 16 (39.0%) | 31 (36.9%) | |
| Prior overlapping radiation, n (%) | .0685* | |||
| No | 33 (76.7%) | 38 (92.7%) | 71 (84.5%) | |
| Yes | 10 (23.3%) | 3 (7.3%) | 13 (15.5%) | |
| Radiation site | .9611* | |||
| Intact breast | 16 (37.2%) | 14 (34.1%) | 30 (35.7%) | |
| Chest wall, no reconstruction | 10 (23.3%) | 11 (26.8%) | 21 (25.0%) | |
| Chest wall w/ any reconstruction† | 17 (39.5%) | 16 (39.0%) | 33 (39.3%) | |
| Skin rind structure for skin dose evaluation, n (%) | 1.0000* | |||
| 5 mm | 15 (34.9%) | 15 (36.6%) | 30 (35.7%) | |
| 3 mm | 28 (65.1%) | 26 (63.4%) | 54 (64.3%) | |
| Dose fractionation, n (%) | .0459* | |||
| Moderate hypofractionation | 6 (14.0%) | 1 (2.4%) | 7 (8.3%) | |
| Conventional fractionation | 35 (81.4%) | 40 (97.6%) | 75 (89.3%) | |
| Hyperfractionation/twice a day | 2 (4.7%) | 0 (0.0%) | 2 (2.4%) | |
| Receipt of boost treatment, n (%) | .3559* | |||
| No | 31 (72.1%) | 25 (61.0%) | 56 (66.7%) | |
| Yes | 12 (27.9%) | 16 (39.0%) | 28 (33.3%) |
Fisher exact test.
Includes auto/expander/direct implant.
Treatment plan characteristics overall and between groups planned without and with an SSPT are shown in Table 2. Plans developed without an SSPT had a significantly higher mean skin-evalV95%Rx compared with plans developed with an SSPT (72% vs 30%, P < .0001). Maximum %Rx to the skin volume of 0.03, 0.3, and 1 cc was higher in patients planned without compared to those with an SSPT (103.1% vs 101.5%; 101.3% vs 100.4%; and 101.8% vs 99.7% [all P < .0001]), respectively. There were small but statistically significant differences in the mean volume CTV breast/CW target coverage at 95%Rx (99.2% vs 98.9%, P = .0054) and 97.5%Rx (97.8% vs 96.5%, P = .0003) between the cohorts planned without and with an SSPT. However, both cohorts consistently surpassed the target dose coverage constraints for plan acceptability for treatment at our institution of V95%Rx ≥ 95% (goal ≥ 97.5%). There were no differences in plan heterogeneity (1.06 vs 1.06, P = .2576), mean heart dose (0.56 vs 0.46 Gy, P = .3631), or percentage of ipsilateral lung dose (volume receiving 20/16 Gy [conventional/hypofractionated radiation]: 11.9% vs 12.5%, P = .4796) in patients treated without and with SSPT. There were no differences between the cohorts in the projected doses of the robustly optimized scenarios of 5 mm shifts and 3% range uncertainty and number of plans not meeting the idealized constraint of V95% of the target receiving V95%Rx in all robust evaluation scenarios (P > .05).
Table 2.
Treatment plan characteristics overall and between groups of those treated without and with a skin-sparing planning technique
| Characteristics | Patients treated without volumetric skin-sparing (N = 43) |
Patients treated with volumetric skin-sparing (N = 41) |
Total (N = 84) |
P value |
|---|---|---|---|---|
| Skin max 0.03 cc (%Rx) | .0001* | |||
| N | 43 | 41 | 84 | |
| Mean (±SD) | 103.1 (2.59) | 101.5 (1.35) | 102.3 (2.21) | |
| Median | 102.8 | 101.2 | 102.0 | |
| Range | 100.1, 116.8 | 98.8, 104.7 | 98.8, 116.8 | |
| Skin max 0.3 cc (%Rx) | <.0001* | |||
| N | 43 | 41 | 84 | |
| Mean (±SD) | 101.3 (7.09) | 100.4 (1.36) | 100.8 (5.16) | |
| Median | 102.2 | 100.3 | 101.1 | |
| Range | 58.6, 115.2 | 97.5, 103.7 | 58.6, 115.2 | |
| Skin max 1 cc (%Rx) | <.0001* | |||
| N | 43 | 41 | 84 | |
| Mean (SD) | 101.8 (2.34) | 99.7 (1.50) | 100.8 (2.23) | |
| Median | 101.9 | 99.5 | 100.7 | |
| Range | 98.3, 114.1 | 96.8, 103.1 | 96.8, 114.1 | |
| Skin V95%Rx of skin-eval (%) | <.0001* | |||
| N | 43 | 41 | 84 | |
| Mean (±SD) | 71.5 (19.80) | 29.5 (16.78) | 51.0 (27.94) | |
| Median | 73.6 | 25.8 | 48.4 | |
| Range | 25.8, 99.9 | 7.3, 69.6 | 7.3, 99.9 | |
| Target (CTVbreast/CTVChestwall) volume receiving 97.5% Rx | .0003* | |||
| N | 43 | 41 | 84 | |
| Mean (±SD) | 97.8 (3.61) | 96.5 (3.16) | 97.2 (3.44) | |
| Median | 99.1 | 96.3 | 98.2 | |
| Range | 82.5, 100.0 | 81.3, 99.7 | 81.3, 100.0 | |
| Target (CTVbreast/CTVChestwall) volume receiving 95% Rx | .0054* | |||
| N | 43 | 41 | 84 | |
| Mean (SD) | 99.2 (1.40) | 98.9 (1.26) | 99.1 (1.34) | |
| Median | 99.8 | 99.1 | 99.6 | |
| Range | 93.8, 100.0 | 94.1, 100.0 | 93.8, 100.0 | |
| Heterogeneity (%Rx)† | .2576* | |||
| N | 43 | 41 | 84 | |
| Mean (±SD) | 1.06 (0.02) | 1.06 (0.04) | 1.06 (0.03) | |
| Median | 1.06 | 1.06 | 1.06 | |
| Range | 1.02, 1.18 | 1.03, 1.30 | 1.002, 1.30 | |
| Mean heart dose (Gy) | .3613* | |||
| N | 0.43 | 0.41 | 0.84 | |
| Mean (±SD) | 0.56 (0.43) | 0.46 (0.33) | 0.52 (0.38) | |
| Median | 0.53 | 0.42 | 0.46 | |
| Range | 0.0, 1.97 | 0.03, 1.35 | 0.0, 1.97 | |
| Lung dose % | .4796‡ | |||
| N | 43 | 41 | 84 | |
| Mean (±SD) | 11.9 (6.94) | 12.5 (4.36) | 12.2 (5.80) | |
| Median | 12.7 | 12.6 | 12.7 | |
| Range | 0.0, 33.8 | 3.1, 19.7 | 0.0, 33.8 | |
| Worst case prediction plan on robust evaluation target volume receiving 95%Rx | .1627* | |||
| N | 43 | 41 | 84 | |
| Mean (±SD) | 97.1 (3.21) | 96.6 (3.13) | 96.8 (3.16) | |
| Median | 97.9 | 97.7 | 97.8 | |
| Range | 82.1, 99.7 | 83.7, 99.7 | 82.1, 99.7 | |
| Number of robust evaluation scenarios failing to meet goal criteria‡, n (%) | .5663§ | |||
| 0 | 37 (86.0%) | 33 (80.5%) | 70 (83.3%) | |
| 1 | 6 (14.0%) | 8 (19.5%) | 14 (16.7%) |
Abbreviations: CTV = clinical target volume; SD = standard deviation; %Rx = percentage of the prescription dose.
Wilcoxon rank sum test.
Plan Heterogeneity is defined as a maximum dose of 0.03 cc within the target (CTVbreast or CTVChestwall) expressed as a percentage of the prescription dose.
Exact Kruskal-Wallis P value.
Fisher's exact test.
The acute on-treatment breast pain and dermatitis rates for the first 5 weeks of treatment are reported in Table 3. Patients planned to use the SSPT demonstrated reduced rates of grade 1 breast pain at week 2 (12% vs 33%, P = .0424) and grades 2 and 3 dermatitis at weeks 4 and 5 (week 4 dermatitis ≥ grade 2, 18% vs 43%, P = .0224; week 5 dermatitis ≥ grade 2, 45% vs 69%, P = .0006). Weeks 4 and 5 dermatitis toxicity grading was separated based on attribution to erythema and desquamation as shown in Table 4, revealing that the increase in dermatitis grading was driven largely by suggestions of increased erythema in the patients treated without SSPT (week 4 erythema ≥ grade 2, 38% vs 15%, P = .0511; week 5 erythema ≥ grade 2, 69% vs 43%, P = .0081). In patients treated without an SSPT, by week 5 of treatment there was a trend toward increased rates of desquamation grade 2 ≥ 67% vs 38%, P = .0889).
Table 3.
On-treatment toxicity between groups of those treated without and with a skin-sparing planning technique
| Patients treated without volumetric skin-sparing (N = 43) |
Patients treated with volumetric skin-sparing (N = 41) |
Total (N = 84) |
P value | |||
|---|---|---|---|---|---|---|
| Week 1 breast pain*, n (%) | .1978† | |||||
| Grade 0 | 35 (81.4%) | 33 (80.5%) | 68 (81.0%) | |||
| Grade 1 | 3 (7.0%) | 7 (17.1%) | 10 (11.9%) | |||
| Grade 2 | 4 (9.3%) | 1 (2.4%) | 5 (6.0%) | |||
| Grade 3 | 1 (2.3%) | 0 (0.0%) | 1 (1.2%) | |||
| Week 2 breast pain*, n (%) | .0424† | |||||
| Grade 0 | 28 (65.1%) | 35 (85.4%) | 63 (75.0%) | |||
| Grade 1 | 14 (32.6%) | 5 (12.2%) | 19 (22.6%) | |||
| Grade 2 | 1 (2.3%) | 1 (2.4%) | 2 (2.4%) | |||
| Grade 3 | 0 (0%) | 0 (0%) | 0 (0%) | |||
| Week 3 breast pain*, n (%) | .4626† | |||||
| Grade 0 | 34 (79.1%) | 29 (70.7%) | 63 (75.0%) | |||
| Grade 1 | 6 (14.0%) | 10 (24.4%) | 16 (19.0%) | |||
| Grade 2 | 2 (4.7%) | 2 (4.9%) | 4 (4.8%) | |||
| Grade 3 | 1 (2.3%) | 0 (0.0%) | 1 (1.2%) | |||
| Week 4 breast pain*, n (%) | .972† | |||||
| Grade 0 | 23 (57.5%) | 25 (62.5%) | 48 (60.0%) | |||
| Grade 1 | 11 (27.5%) | 9 (22.5%) | 20 (25.0%) | |||
| Grade 2 | 5 (12.5%) | 5 (12.5%) | 10 (12.5%) | |||
| Grade 3 | 1 (2.5%) | 1 (2.5%) | 2 (2.5%) | |||
| Patients off treatment‡ | 3 | 1 | 4 | |||
| Week 5 breast pain*, n (%) | .3499† | |||||
| Grade 0 | 15 (40.5%) | 21 (52.5%) | 36 (46.8%) | |||
| Grade 1 | 14 (37.8%) | 16 (40.0%) | 30 (39.0%) | |||
| Grade 2 | 6 (16.2%) | 2 (5.0%) | 8 (10.4%) | |||
| Grade 3 | 2 (5.4%) | 1 (2.5%) | 3 (3.9%) | |||
| Patients off treatment‡ | 6 | 1 | 7 | |||
| Week 1 dermatitis§, n (%) | .7799† | |||||
| Grade 0 | 36 (83.7%) | 33 (80.5%) | 69 (82.1%) | |||
| Grade 1 | 7 (16.3%) | 8 (19.5%) | 15 (17.9%) | |||
| Grade 2 | ||||||
| Week 2 dermatitis§, n (%) | .1803† | |||||
| Grade 0 | 17 (39.5%) | 23 (56.1%) | 40 (47.6%) | |||
| Grade 1 | 25 (58.1%) | 16 (39.0%) | 41 (48.8%) | |||
| Grade 2 | 1 (2.3%) | 2 (4.9%) | 3 (3.6%) | |||
| Week 3 dermatitis§, n (%) | .8265† | |||||
| Grade 0 | 8 (18.6%) | 5 (12.2%) | 13 (15.5%) | |||
| Grade 1 | 33 (76.7%) | 34 (82.9%) | 67 (79.8%) | |||
| Grade 2 | 2 (4.7%) | 2 (4.9%) | 4 (4.8%) | |||
| Week 4 dermatitis§, n (%) | .0224† | |||||
| Grade 0* | 2 (5.0%) | 1 (2.5%) | 3 (3.8%) | |||
| Grade 1 | 21 (52.5%) | 32 (80.0%) | 53 (66.3%) | |||
| Grade 2 | 17 (42.5%) | 7 (17.5%) | 24 (30.0%) | |||
| Completed treatment‡ | 3 | 1 | 4 | |||
| Week 5 dermatitis§, n (%) | .0006† | |||||
| Grade 0* | 5 (13.9%) | 0 (0.0%) | 5 (6.6%) | |||
| Grade 1 | 6 (16.7%) | 22 (55.0%) | 28 (36.8%) | |||
| Grade 2 | 21 (58.3%) | 16 (40.0%) | 37 (48.7%) | |||
| Grade 3 | 4 (11.1%) | 2 (5.0%) | 6 (7.9%) | |||
| Completed treatment‡ | 7 | 1 | 8 | |||
| Treatment break or incomplete treatment), n (%) | .3604† | |||||
| No | 39 (90.7%) | 40 (97.6%) | 79 (94.0%) | |||
| Yes | 4 (9.3%) | 1 (2.4%) | 5 (6.0%) | |||
Breast pain grading.
Fisher's exact test; 0 = none; 1 = mild, 2 = moderate; and 3 = severe.
Patients off treatment because of completion of hypofractionated radiation course.
Dermatitis grading; 0 = none; 1 = faint erythema or dry desquamation; 2 = moderate to brisk erythema; patchy moist desquamation, confined mainly to skin folds and creases, moderate edema; and 3 = moist desquamation in areas other than skin folds and creases.
Table 4.
Week 4 and week 5 on-treatment dermatitis graded as erythema or desquamation between groups of those treated without and with a skin-sparing planning technique
| Volumetric constraints part of the initial clinical goal? (0 = no, 1 = yes) |
||||
|---|---|---|---|---|
| 0 (N = 43) | 1 (N = 41) | Total (N = 84) | P value | |
| Week 4 erythema*, n (%) | .0511† | |||
| Grade 0 | 3 (7.5%) | 2 (5.0%) | 5 (6.3%) | |
| Grade 1 | 22 (55.0%) | 32 (80.0%) | 54 (67.5%) | |
| Grade 2 | 15 (37.5%) | 6 (15.0%) | 21 (26.3%) | |
| Completed treatment‡ | 3 | 1 | 4 | |
| Week 5 erythema*, n (%) | .0081† | |||
| Grade 0 | 3 (8.3%) | 1 (2.5%) | 4 (5.3%) | |
| Grade 1 | 8 (22.2%) | 22 (55.0%) | 30 (39.5%) | |
| Grade 2 | 25 (69.4%) | 17 (42.5%) | 42 (55.3%) | |
| Completed treatment‡ | 7 | 1 | 8 | |
| Max erythema*, n (%) | .0473† | |||
| Grade 0 | 1 (2.3%) | 0 (0.0%) | 1 (1.2%) | |
| Grade 1 | 14 (32.6%) | 23 (56.1%) | 37 (44.0%) | |
| Grade 2 | 28 (65.1%) | 18 (43.9%) | 46 (54.8%) | |
| Week 4 desquamation§, n (%) | 1.0000† | |||
| Grade 0 | 37 (92.5%) | 37 (92.5%) | 74 (92.5%) | |
| Grade 1 | 3 (7.5%) | 2 (5.0%) | 5 (6.3%) | |
| Grade 2 | 0 (0.0%) | 1 (2.5%) | 1 (1.3%) | |
| Completed treatment‡ | 3 | 1 | 4 | |
| Week 5 desquamation§, n (%) | .0889† | |||
| Grade 0 | 3 (8.3%) | 6 (15.0%) | 9 (11.8%) | |
| Grade 1 | 9 (25.0%) | 19 (47.5%) | 28 (36.8%) | |
| Grade 2 | 20 (55.6%) | 13 (32.5%) | 33 (43.4%) | |
| Grade 3 | 4 (11.1%) | 2 (5.0%) | 6 (7.9%) | |
| Completed treatment‡ | 7 | 1 | 8 | |
| Max desquamation§, n (%) | .0656† | |||
| Grade 0 | 10 (23.3%) | 6 (14.6%) | 16 (19.0%) | |
| Grade 1 | 9 (20.9%) | 20 (48.8%) | 29 (34.5%) | |
| Grade 2 | 20 (46.5%) | 13 (31.7%) | 33 (39.3%) | |
| Grade 3 | 4 (9.3%) | 2 (4.9%) | 6 (7.1%) | |
Erythema grading; 0 = none; 1 = faint erythema; and 2 = moderate to brisk erythema.
Fisher's exact test.
Patients off treatment because of to completion of the hypofractionated radiation course.
Desquamation grading; 0 = none; 1 = dry desquamation; 2 = patchy moist desquamation, confined mainly to skin folds and creases; and 3 = moist desquamation in areas other than skin folds and creases.
Although the difference did not approach statistical significance, there were numerically more patients in the cohort treated without an SSPT who required a treatment break or did not complete their full course of treatment (4 patients [9%] vs 1 patient [2%]) because of the severity of acute dermatitis.
Discussion
This retrospective cohort study presents outcomes of a volumetric-based SSPT for PBS-treated breast cancer patients. Our study found that a volumetric-based skin-eval V95%Rx < 50% objective appears consistently achievable while maintaining exceptional nominal and robustly optimized target coverage in patients receiving PBS to the breast and CW. Although a statistically significant difference was noted between CTV breast and CW target coverage, the resultant CTV coverage was consistently greater than our ideal V97.5%Rx > 97.5% and well above our mandatory V95%Rx > 95% for clinical acceptability. Thus, this difference is not felt to be clinically significant. Both cohorts demonstrated similar target coverage rates in robustly optimized scenarios, indicating the ability for robust plan delivery despite the use of SSPT to create a gradient on the skin, reducing the risk of toxicity.
Early studies using passive scatter proton therapy report high rates of skin toxicity.9,13 However, even with more advanced techniques, including the incorporation of multifield, PBS proton therapy, higher rates of grade ≥ 2 radiation dermatitis in patients treated with PBT than those with photon radiation (27% vs 14%, respectively, P ≤ .001) have been observed.14
We demonstrate improvements with PBS PBT that can reduce skin toxicity for patients while providing the advantage of reduced exposure to the heart, lungs, and adjacent musculoskeletal structures compared to photon radiation. The methodology used is consistently achievable and replicable across institutions and treatment planning systems. While the study reports positive findings and supports the use of this method, it is limited by a small sample size and the inherent flaws of a single-center, retrospective design. Additional studies with larger sample sizes, consistent 1- to 2-week posttreatment follow-up, and long-term follow-up with protocolized skin care are needed to further study this strategy's impact on reducing treatment-related toxicity with PBS. Furthermore, as liner energy transfer and relative biological effectiveness-based planning tools become more widely available, further investigation is warranted to evaluate the impact of SSPT both on the nominal dose distribution and liner energy transfer and relative biological profiles of the dose on the skin and target.
Disclosures
None.
Acknowledgments
Hongkun Wang performed the statistical analysis.
Footnotes
Sources of support: Dr Gary D. and Christina Co Mather.
Research data are stored in an institutional repository and will be shared on request to the corresponding author.
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