Reduction of cardiac dose using respiratory-gated MR-linac plans for gastro-esophageal junction cancer.

Treatment of locally advanced adenocarcinoma of the gastroesophageal junction (GEJ) with chemoradiation may be associated with high rates of symptomatic cardiac toxicity. Large margins are typically required to ensure coverage of GEJ tumors with free-breathing volumetric modulated arc therapy (VMAT) radiotherapy. The purpose of this study is to determine whether treatment with tighter margins enabled by maximum-inhalation breath hold (MIBH)-gated intensity modulated radiation therapy (IMRT) on an integrated MRI-linear accelerator system (MR-linac) can decrease radiation doses to the heart and cardiac substructures. Ten patients with locally advanced GEJ adenocarcinoma underwent both free breathing 4-dimensional computed tomography (4DCT) and MIBH MRI simulation scans. MR-linac IMRT plans were created with a 3 mm clinical target volume (CTV) to planning target volume (PTV) isotropic margin and 4DCT VMAT plans were created with a 11, 13, and 9 mm CTV to PTV anisotropic margins in the left-right, cranial-caudal, and anterior-posterior directions according to GEJ-specific PTV expansion recommendations by Voncken et al. Prescription dose to PTV was 50.4 Gy in 28 fractions. Dosimetry to the heart and cardiac substructures was compared with paired t test; p < 0.05 was considered significant. Mean PTV on the MR-linac IMRT plans was significantly smaller compared to the 4DCT VMAT plans (689 cm3vs 1275 cm3, p < 0.01). Mean dose to the heart and all cardiac substructures was significantly lower in the MR-linac IMRT plans compared to the 4DCT VMAT plans: heart 20.9 Gy vs 27.8 Gy, left atrium 29.6 Gy vs 39.4 Gy, right atrium 20.5 Gy vs 25.6 Gy, left ventricle 21.6 Gy vs 29.6 Gy, and right ventricle 18.7 Gy vs 25.2 Gy (all p values <0.05). MIBH-gated MR-linac IMRT treatment of locally advanced GEJ adenocarcinoma can significantly decrease doses to the heart and cardiac substructures and this may translate to reduced rates of cardiac toxicity.

Evaluating dose constraints for radiation induced liver damage following magnetic resonance image guided Stereotactic Body radiotherapy.

This study reports dose corresponding to visible radiation induced liver damage following Stereotactic Body Radiation Therapy (SBRT) for liver metastasis, and the optimal time for follow up scans using post radiation imaging. Diagnostic magnetic resonance scans of nine patients treated with liver SBRT using a 0.35 T MRI-guided radiotherapy system were analyzed. The dice coefficients between the region of visible liver damage and the delivered dose were calculated. A median dose of 35 Gy correlated most closely with the visible radiation induced liver damage. We compared scans over two to nine months and observed maximal dice coefficients at two to five months post radiation. We have presented a new method for developing treatment planning guidelines for liver SBRT.

Pulsed reduced dose-rate radiotherapy: a novel locoregional retreatment strategy for breast cancer recurrence in the previously irradiated chest wall, axilla, or supraclavicular region.

PURPOSE: Reirradiation of breast cancer locoregional recurrence (LRR) in the setting of prior post-mastectomy radiation poses a significant clinical challenge due to the high risk for severe toxicity. In an attempt to reduce these toxicities, we have developed pulsed reduced dose-rate radiotherapy (PRDR), a reirradiation technique in which a series of 0.2 Gy pulses separated by 3-min time intervals is delivered, creating an apparent dose rate of 0.0667 Gy/min. Here we describe our early experience with PRDR. PATIENTS AND METHODS: We reirradiated 17 patients with LRR breast cancer to the chest wall, axilla, or supraclavicular region using PRDR. The median prior radiation dose was 60 Gy. We delivered a median PRDR dose of 54 Gy (range 40-66 Gy) in 1.8-2.0 Gy per fraction. Eight patients received concomitant low dose capecitabine for radiosensitization. The median treatment volume was 2,084 cm(3) (range 843-7,881 cm(3)). RESULTS: At a median follow-up of 18 months (range 4-75 months) only 2 patients have had tumor failure in the treatment region. Estimated 2-year local control rate is 92%. Treatment was well tolerated with 4 patients experiencing grade 3 acute skin toxicity. Despite a median cumulative dose of 110 Gy (range 80-236 Gy), there has been only one grade 3 and one grade 4 late toxicity. CONCLUSIONS: With a median follow-up of 18 months, PRDR appears to be an effective method to reirradiate large volumes of previously irradiated tissue in selected patients with locoregional chest wall, axilla, and supraclavicular recurrences.

Postmastectomy radiotherapy in premenopausal Vietnamese and Chinese women with breast cancer treated in an adjuvant hormonal therapy study.

BACKGROUND: Adjuvant postmastectomy radiotherapy (RT) decreases the risk of local recurrence of breast cancer and may increase overall survival (OS). METHODS AND MATERIALS: After mastectomy, 656 premenopausal Vietnamese and Chinese women with clinical Stage II-IIIA breast cancer, in a clinical trial of adjuvant surgical oophorectomy and tamoxifen, were treated with adjuvant RT according to the availability in the institution. The short-term disease recurrence and OS experience of these 656 women were analyzed using univariate and multivariate methods. RESULTS: The 193 patients who did not receive RT differed from the 463 who did in that they had larger tumors and more frequently Grade 3 tumors. With a median follow-up of 3.6 years, in univariate analysis, RT was associated with improved disease-free survival (DFS) (relative risk 0.66; 95% confidence interval 0.49-0.89; p = 0.007) and OS (relative risk 0.71; 95% confidence interval 0.50-1.00; p = 0.051). In multivariate analysis, the relative risk for DFS and OS associated with RT was 0.78 and 0.94, respectively (p = not significant for both). Kaplan-Meier estimates showed better 5-year DFS (72% vs. 59%; p = 0.006) and OS (78% vs. 70%; p = 0.05) rates with RT. CONCLUSION: In the absence of detailed CT planning capacity, adjuvant RT for premenopausal Vietnamese women was associated statistically with short-term improvement in DFS and OS in univariate, but not multivariate, analysis.

Reirradiation of large-volume recurrent glioma with pulsed reduced-dose-rate radiotherapy.

PURPOSE: Pulsed reduced-dose-rate radiotherapy (PRDR) is a reirradiation technique that reduces the effective dose rate and increases the treatment time, allowing sublethal damage repair during irradiation. PATIENTS AND METHODS: A total of 103 patients with recurrent glioma underwent reirradiation using PRDR (86 considered to have Grade 4 at PRDR). PRDR was delivered using a series of 0.2-Gy pulses at 3-min intervals, creating an apparent dose rate of 0.0667 Gy/min to a median dose of 50 Gy (range, 20-60) delivered in 1.8-2.0-Gy fractions. The mean treatment volume was 403.5±189.4 cm3 according to T2-weighted magnetic resonance imaging and a 2-cm margin. RESULTS: For the initial or upgraded Grade 4 cohort (n=86), the median interval from the first irradiation to PRDR was 14 months. Patients undergoing PRDR within 14 months of the first irradiation (n=43) had a median survival of 21 weeks. Those treated ≥14 months after radiotherapy had a median survival of 28 weeks (n=43; p=0.004 and HR=1.82 with a 95% CI ranging from 1.25 to 3.10). These data compared favorably to historical data sets, because only 16% of the patients were treated at first relapse (with 46% treated at the second relapse, 32% at the third or fourth relapse, and 4% at the fourth or fifth relapse). The median survival since diagnosis and retreatment was 6.3 years and 11.4 months for low-grade, 4.1 years and 5.6 months for Grade 3, and 1.6 years and 5.1 months for Grade 4 tumors, respectively, according to the initial histologic findings. Multivariate analysis revealed age at the initial diagnosis, initial low-grade disease, and Karnofsky performance score of ≥80 to be significant predictors of survival after initiation of PRDR. CONCLUSION: PRDR allowed for safe retreatment of larger volumes to high doses with palliative benefit.