Effect of Supine vs Prone Breast Radiotherapy on Acute Toxic Effects of the Skin Among Women With Large Breast Size: A Randomized Clinical Trial.

Importance: Women with large breast size treated with adjuvant breast radiotherapy (RT) have a high rate of acute toxic effects of the skin. Breast RT in the prone position is one strategy that may decrease these toxic effects. Objective: To determine if breast RT in the prone position reduces acute toxic effects of the skin when compared with treatment in the supine position. Design, Setting, and Participants: This phase 3, multicenter, single-blind randomized clinical trial accrued patients from 5 centers across Canada from April 2013 to March 2018 to compare acute toxic effects of breast RT for women with large breast size (bra band ≥40 in and/or ≥D cup) in the prone vs supine positions. A total of 378 patients were referred for adjuvant RT and underwent randomization. Seven patients randomized to supine position were excluded (5 declined treatment and 2 withdrew consent), and 14 patients randomized to prone position were excluded (4 declined treatment, 3 had unacceptable cardiac dose, and 7 were unable to tolerate being prone). Data were analyzed from April 2019 through September 2020. Interventions: Patients were randomized to RT in the supine or prone position. From April 2013 until June 2016, all patients (n = 167) received 50 Gy in 25 fractions (extended fractionation) with or without boost (range, 10-16 Gy). After trial amendment in June 2016, the majority of patients (177 of 190 [93.2%]) received the hypofractionation regimen of 42.5 Gy in 16 fractions. Main Outcomes and Measures: Main outcome was moist desquamation (desquamation). Results: Of the 357 women (mean [SD] age, 61 [9.9] years) included in the analysis, 182 (51.0%) were treated in the supine position and 175 (49.0%) in prone. There was statistically significantly more desquamation in patients treated in the supine position compared with prone (72 of 182 [39.6%] patients vs 47 of 175 [26.9%] patients; OR, 1.78; 95% CI, 1.24-2.56; P = .002), which was confirmed on multivariable analysis (OR, 1.99; 95% CI, 1.48-2.66; P < .001), along with other independent factors: use of boost (OR, 2.71; 95% CI, 1.95-3.77; P < .001), extended fractionation (OR, 2.85; 95% CI, 1.41-5.79; P = .004), and bra size (OR, 2.56; 95% CI, 1.50-4.37; P < .001). Conclusions and Relevance: This randomized clinical trial confirms that treatment in the prone position decreases desquamation in women with large breast size receiving adjuvant RT. It also shows increased toxic effects using an RT boost and conventional fractionation. Trial Registration: ClinicalTrials.gov Identifier: NCT01815476.

Introduction of moderate deep inspiration breath hold for radiation therapy of left breast: Initial experience of a regional cancer center.

PURPOSE: Practical aspects of introducing moderate deep inspiration breath hold (mDIBH) for treatment of left breast cancer in a regional cancer program in terms of workflow and treatment delivery requirements are described. Differences in heart and lung doses between free breathing (FB) and mDIBH plans are presented as well as heart position reproducibility and resulting dosimetric impact using cone beam computed tomography (CBCT). METHODS AND MATERIALS: A mDIBH process was established. Therapists observed duration and quantity of breath holds required for setup, imaging, and beam delivery during treatment. Treatment plans were generated on the FB and mDIBH CT datasets allowing comparison of heart and lung dose-volume data for 50 patients. Five consecutive CBCT images were used to measure the distance between the heart and chest wall for 5 patients. Estimates of dose to the translated heart were then made with the treatment planning system. RESULTS: When compared with FB delivery, mDIBH treatment time for tangents and boosts increased by 5 minutes, while 3- or 4-field techniques increased by 10 minutes. Differences in heart dose D10 cc, mean, V30 and V10 were statistically significant between the FB and mDIBH tangents and 3- or 4-field treatment plans. Statistically significant differences in V20, V10, V5, and mean lung doses were observed for 3- and 4-field FB and mDIBH plans. Differences between lung V5 dose metrics for FB and mDIBH 2-field plans were statistically significant. Interfraction mean translations in heart position coronally ranged from -6.2 to 2.6 mm and resulted in non-negligible increases in the heart dose. CONCLUSIONS: Moderate deep inspiration breath hold has been successfully implemented in our regional cancer center for treatment of left breast cancer and is now a standard practice. This change in practice from FB to mDIBH treatment has not impacted our ability to meet provincial guidelines for patient throughput.

Evaluation of variability in seroma delineation between clinical specialist radiation therapist and radiation oncologist for adjuvant breast irradiation.

PURPOSE: Breast cancer is managed by a multidisciplinary team with a goal for the timely provision of high quality care. Given radiation oncologist (RO) time constraints, an opportunity arises for task delegation of breast seroma target delineation to an advanced practice clinical specialist radiation therapist (CSRT) with clinical and technical expertise to facilitate treatment planning. To explore this further, we quantitatively evaluated the variability in post-surgical seroma delineation between the CSRT and ROs. METHODS: Specialized site specific training was provided to the CSRT, who, with 7 ROs, independently contoured the seroma and graded its clarity, using the cavity visualization score (CVS), for 20 patients with clinical stage Tis-2N0 breast tumors. The conformity indices were analyzed for all possible pairs of delineations. The estimated "true" seroma contour was derived from the RO contours using the simultaneous truth and performance level estimation algorithm. Generalized kappa coefficient and center of mass metrics were used to examine the performance level of the CSRT in seroma delineations. RESULTS: The CVS of the CSRT correlated well with the mean RO-group CVS, (Spearman ρ = 0.87, P < .05). The mean seroma conformity index for the RO group was 0.61 and 0.65 for the CSRT; a strong correlation was observed between the RO and CSRT conformity indices (Spearman ρ = 0.95, P < .05). Almost perfect agreement levels were observed between the CSRT contours and the STAPLE RO consensus contours, with an overall kappa statistic of 0.81 (P < .0001). The average center of mass shift between the CSRT and RO consensus contour was 1.69 ± 1.13 mm. CONCLUSIONS: Following specialized education and training, the CSRT delineated seroma targets clinically comparable with those of the radiation oncologists in women with early breast tumors suitable for accelerated partial breast or whole breast radiotherapy following lumpectomy. This study provides support for potential task delegation of breast seroma delineation to the CSRT in our current multidisciplinary environment. Further study is needed to assess the impact of this role expansion on radiotherapy system efficiency.

Parametrial boost using midline shielding results in an unpredictable dose to tumor and organs at risk in combined external beam radiotherapy and brachytherapy for locally advanced cervical cancer.

PURPOSE: Midline-blocked boost (MBB) fields are frequently used in the treatment of locally advanced cervical cancer. The purpose of this study was to evaluate the dose contribution from MBBs to tumor and organs at risk. METHODS AND MATERIALS: Six patients with locally advanced cervical cancer (IIB-IIIB) treated with definitive chemoradiotherapy and magnetic resonance imaging (MRI)-guided brachytherapy were analyzed. A three-phase plan was modeled: 45 Gy (1.8 Gy per fraction) four-field box, 9 Gy (1.8 Gy per fraction) MBB (midline-shielded anteroposterior/posteroanterior fields), and intracavitary MRI-guided brachytherapy boost of 28 Gy (7 Gy per fraction). Midline shields 3, 4, and 5 cm wide were simulated for each patient. Brachytherapy and MBB plans were volumetrically summed. The rectum, sigmoid, and bladder minimum dose in the most exposed 2 cm(3) of an organ at risk (D(2 cc)) and high-risk clinical target volume (HR-CTV) and intermediate-risk clinical target volume (IR-CTV) D90 and D100 were evaluated. The intended HR-CTV D90 was 85 Gy or greater, and the intended IR-CTV D90 was greater than 60 Gy. RESULTS: After a 4-cm MBB, HR-CTV D90 remained lower than 85 Gy in all cases (mean, 74 Gy; range, 64-82 Gy). High-risk clinical target volume (85 Gy) coverage increased slightly from 73% (range, 64-82%) to 78% (range, 69-88%). Mean IR-CTV D90 increased from 56 Gy (range, 53-64 Gy) to 62 Gy (range, 59-67 Gy). Intermediate-risk clinical target volume 60-Gy dose coverage increased from 81% (range, 72-96%) to 96% (range, 90-100%). The mean volume irradiated to 85 Gy increased by 14 cm(3) (range, 10-22 cm(3)), whereas the volume irradiated to 60 Gy increased from 276 cm(3) (range, 185-417 cm(3)) to 592 cm(3) (range, 385-807 cm(3)). Bladder, rectum, or sigmoid D(2 cc) increased by more than 50% of the boost dose in 4 of 6 patients. CONCLUSIONS: Midline-blocked boosts contribute substantial dose to rectum, sigmoid, and bladder D(2 cc). HR-CTV dose and 85-Gy coverage remain compromised in large tumors despite MBB. IR-CTV 60-Gy coverage improved at the expense of a considerable increase in volume of normal tissue irradiated to 60 Gy.

Dosimetric comparison of IMRT vs. 3D conformal radiotherapy in the treatment of cancer of the cervical esophagus.

BACKGROUND AND PURPOSE: Radiotherapy planning for cervical esophageal cancer is challenging. We compared IMRT and 3D conformal radiotherapy (CRT) with respect to conformality of target coverage and normal tissue sparing. MATERIALS AND METHODS: We selected five patients with cervical esophagus cancer, who represented the heterogeneity of clinical cases, treated to radical dose and planned with Pinnacle v6.2. Target doses for CRT plans were 50, 60, and 70Gy (single-phase IMRT 56, 63, and 70). We compared PTV coverage by the 95% isodose (PTV(95)), conformality ratio (CR), conformation number (CN), and maximum or mean doses (D(max), D(mean)) to normal structures. RESULTS: Median PTV(95) for IMRT plans for PTV70, PTV63, and PTV56 were 97%, 99%, and 98% (CRT 91%, 98%, and 85%). IMRT plans demonstrated lower D(max) to the spinal cord and brainstem (42 and 36Gy) compared to CRT (46 and 39Gy). Median left parotid D(mean) was 35Gy (IMRT) vs. 53Gy (CRT). Median right parotid D(mean) was 35Gy (IMRT) vs. 36Gy (CRT). The median CR50/56Gy was 1.4 (CRT) vs. 1.2 (IMRT), CR70Gy 1.7 (CRT) vs. 1.1 (IMRT). CN50/56 and CN70 values were 0.80 and 0.85 (IMRT) vs. 0.56 and 0.5 (CRT). CONCLUSIONS: IMRT provides superior target volume coverage and conformality, with decreased dose to normal structures.

Arterial repair after stenting and the effects of GM6001, a matrix metalloproteinase inhibitor.

OBJECTIVES: This study compared the extracellular matrix (ECM) and cellular responses after stenting to balloon angioplasty (BA) and to determine the late effects of matrix metalloproteinase (MMP) inhibition on arterial repair after stenting. BACKGROUND: Although stenting is the predominant form of coronary intervention, there is limited understanding of the early and late arterial response. METHODS: In a double-injury rabbit model, adjacent iliac arteries in 87 animals received BA (3.0 mm diameter) or stenting (3.0 mm NIR). Rabbits were treated for 1 week postprocedure with either GM6001 (100 mg/kg per day), an MMP inhibitor or placebo and sacrificed at 1 week or at 10 weeks' postprocedure. Arteries were analyzed for morphometry, collagen content, gelatinase activity, cell proliferation and DNA content. RESULTS: Stented arteries had significant increases in collagen content (2-fold) at 10 weeks compared to BA-treated arteries. At one week, overall gelatinase activity was increased >2-fold in stented arteries, with both 72 kD and 92 kD gelatinase activity. Stented arteries also had increases in both intimal DNA content (1.5-fold) and absolute cell proliferation (4-fold). Compared to placebo, GM6001 significantly inhibited intimal hyperplasia and intimal collagen content, and it increased lumen area in stented arteries without effects on proliferation rates. CONCLUSIONS: Stenting causes a more vigorous ECM and MMP response than BA, which involves all layers of the vessel wall. Inhibition by MMP blocks in-stent intimal hyperplasia and offers a novel approach to prevent in-stent restenosis.