Radiation therapy for oligometastatic bone disease in breast cancer

Breast cancer (BCa) frequently metastasizes to the bone. BCa patients with oligometastatic bone diseases have much more favorable outcomes than those with metastatic bone disease. Radiation therapy (RT), especially stereotactic body radiation therapy (SBRT), is advised for the treatment of patients with oligometastatic bone disease in other primary sites. "This line of treatment provided favorable outcomes in patients and resulted in only mild toxicities. A similar strategy has been suggested for treatment of BCa patients with oligometastatic bone disease. BCa, bone-only, or high radiation dose are reported to have been associated with good outcomes in RT for metastatic disease. Furthermore, based on the guidelines provided by the BCa expert panel of the German Society for Radiation Oncology and members of the Working Party of Gynecologic Oncology Breast Committee and in line of the results obtained in other primary sites, our group supports the use of high-dose RT or SBRT for the treatment of BCa patients with oligometastatic bone disease. Additionally, the use of magnetic resonance imaging (MRI) for proper target volume definition and three-dimensional (3D) treatment planning especially for lesions of the trunk are essential for the treatment planning of RT. Of note, several clinical trials have combined RT with immune checkpoint inhibitors for the treatment of BCa patients with metastatic disease. Based on this, we anticipate that combined RT and ICI may serve as a better treatment modality for BCa patients with oligometastatic bone disease

Radiation pneumonitis after definitive concurrent chemoradiotherapy with cisplatin/docetaxel for non-small cell lung cancer: Analysis of dose-volume parameters

Background: Radiation pneumonitis (RP) is a major pulmonary adverse event of chest radiotherapy. The PACIFIC trial that identified durvalumab as an effective subsequent-line therapy after concurrent chemoradiotherapy (CCRT) found that patients with grade 2 or higher RP may have to be excluded from treatment under certain criteria. The purpose of this study was to investigate the relationship between grade ≥2 RP and the parameters of dose-volume histograms after CCRT with cisplatin/docetaxel for stage III non-small cell lung cancer and conduct a subset analysis of severe RP that can lead to the permanent discontinuation of treatment per the PACIFIC trial criteria to help determine treatment strategy. Methods: We calculated the percentage of the lung volume received at least 5 Gy (V5) and 20 Gy (V20), the mean lung dose (MLD), and the lung volume spared from a 5 Gy dose (VS5) to the total lung volume. Factors affecting the incidence of grade ≥2 RP were identified; severe RP was defined as grade ≥3 as well as grade 2 RP that required ≥10 mg prednisolone for at least 12 weeks. Results: This study included 45 patients. On univariate analysis, all parameters and total lung volume were found to be significant predictors of grade ≥2 RP (P = .001, .003, .03, .004, and .02, respectively). On multivariate analysis, V20 was a significant predictive factor of grade ≥2 RP (P = .007). Severe RP developed in 6 of 37 patients (16.2%) whose V20 values were 35% or lower. On univariate analysis, only V20 was a significant predictor of severe RP in these patients (P = .01). Conclusions: The best approach to reduce the rate of grade ≥2 RP is to maintain the V5, V20, MLD, and VS5 as low as possible during radiotherapy planning in patients receiving definitive CCRT with cisplatin/docetaxel

Lung stereotactic body radiation therapy for elderly patients aged >= 80 years with pathologically proven early-stage non-small cell lung cancer: a retrospective cohort study

Background Stereotactic body radiation therapy (SBRT) is an established therapy for medically inoperable early-stage non-small cell lung cancer (NSCLC). Many elderly patients are medically inoperable owing to comorbidities. Therefore, SBRT may be a useful therapy for elderly patients. However, the application of SBRT for patients aged ≥ 80 years has not been completely elucidated. Therefore, this study aimed to assess the clinical utility of SBRT for elderly patients aged ≥ 80 years with pathologically proven early-stage NSCLC. Methods We retrospectively evaluated the data of patients aged ≥ 80 years with pathologically proven primary NSCLC who underwent SBRT at our institution between January 2009 and March 2020. Treatment outcomes and toxicities were analyzed. We used the Kaplan–Meier method to estimate survival curves and the log-rank test to compare the survival curves. We performed univariate and multivariate Cox regression analyses. p-values  Results Sixty-four patients (65 lesions) were included, and the median follow-up period was 38.7 (range 3.5–95.7) months. The median age was 82.9 (range 80.0–94.8) years. Sixteen patients were medically operable, and 48 patients were medically inoperable. The prescribed dose of SBRT was either 48 Gy in four fractions or 60 Gy in 10 fractions. The median survival time was 60.0 months (95% confidence interval, 43.5–71.1). The 1-, 3-, and 5-year local control, cancer-specific survival, progression-free survival, and overall survival rates were 98.4%, 98.4%, 81.0%, and 88.9%; 90.1%, 93.7%, 58.9%, and 68.3%; and 87.4%, 83.5%, 38.2%, and 47.5%, respectively. Multivariate analysis revealed that inoperability and solid nodules were the predictors of poor overall survival after SBRT in elderly patients. Two patients (3.1%) had grade 3 radiation pneumonitis, and one patient (1.6%) had grade 5 radiation pneumonitis. Conclusions SBRT was feasible in patients aged ≥ 80 years with NSCLC. It achieved good local control with minimal toxicity. SBRT may be beneficial in elderly patients with early-stage NSCLC

Clinical Outcome of Palliative Concurrent Chemoradiotherapy with Cisplatin/Docetaxel for Stage III Non-small Cell Lung Cancer

Palliative concurrent chemoradiotherapy (CCRT) is often administered to patients with stage III non-small cell lung cancer (NSCLC). We investigated the clinical outcomes of patients receiving palliative CCRT for NSCLC. Data of patients with NSCLC who underwent palliative CCRT (n=16), preoperative CCRT plus surgery (n=97), or definitive CCRT (n=48) were evaluated. In all groups, the concurrent chemotherapy regimens consisted of cisplatin and docetaxel. Rates of local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), overall survival (OS), and prognosis were compared. The 2-year rates of LC, DMFS, PFS, and OS in 16 patients who underwent palliative CCRT were 44.4%, 12.5%, 12.5%, and 18.8%, respectively. Univariate analysis showed that palliative CCRT was associated with poor LC (p<0.001), DMFS (p<0.001), PFS (p<0.001), and OS (p<0.001) outcomes in patients who completed CCRT as a preoperative treatment and poor LC (p=0.01), DMFS (p=0.003), PFS (p=0.04), and OS (p=0.004) outcomes in patients who were considered for definitive CCRT. Although there were some long-term survivors, the clinical outcomes of palliative CCRT were significantly inferior to those of the ideal treatments. Therefore, careful determination of the appropriate treatment indications and further studies are warranted

bFGF Regulates PI3-Kinase-Rac1-JNK Pathway and Promotes Fibroblast Migration in Wound Healing

Fibroblast proliferation and migration play important roles in wound healing. bFGF is known to promote both fibroblast proliferation and migration during the process of wound healing. However, the signal transduction of bFGF-induced fibroblast migration is still unclear, because bFGF can affect both proliferation and migration. Herein, we investigated the effect of bFGF on fibroblast migration regardless of its effect on fibroblast proliferation. We noticed involvement of the small GTPases of the Rho family, PI3-kinase, and JNK. bFGF activated RhoA, Rac1, PI3-kinase, and JNK in cultured fibroblasts. Inhibition of RhoA did not block bFGF-induced fibroblast migration, whereas inhibition of Rac1, PI3-kinase, or JNK blocked the fibroblast migration significantly. PI3-kinase-inhibited cells down-regulated the activities of Rac1 and JNK, and Rac1-inhibited cells down-regulated JNK activity, suggesting that PI3-kinase is upstream of Rac1 and that JNK is downstream of Rac1. Thus, we concluded that PI3-kinase, Rac1, and JNK were essential for bFGF-induced fibroblast migration, which is a novel pathway of bFGF-induced cell migration

New field‑in‑field with two reference points method for whole breast radiotherapy: Dosimetric analysis and radiation‑induced skin toxicities assessment

The usefulness of the field‑in‑field with two reference points (FIF w/ 2RP) method, in which the dose reference points are set simultaneously at two positions in the irradiation field and the high‑dose range is completely eliminated, was examined in the present study with the aim of decreasing acute skin toxicity in adjuvant breast radiotherapy (RT). A total of 573 patients with breast cancer who underwent postoperative whole breast RT were classified into 178 cases with wedge (W) method, 142 cases with field‑in‑field without 2 reference points (FIF w/o 2RP) method and 253 cases with FIF w/ 2RP method. Using the FIF w/ 2RP method, the high‑dose range was the lowest among the three irradiation methods. The planning target volume (PTV) V105% and the breast PTV for evaluation (BPe) V105% decreased to 0.09 and 0.10%, respectively. The FIF w/ 2RP method vs. the FIF w/o 2RP method had a strong association (η) with PTV V105% (η=0.79; P<0.001) and BPe V105% (η=0.76; P<0.001). The FIF w/ 2RP method had a significant impact on lowering the skin toxicity grade in weeks 3 and 4, and increasing the occurrence of skin toxicity grade 0. The FIF w/ 2RP method vs. the W method had a moderate association with skin toxicity grade at week 3 (η=0.49; P<0.001). Using the FIF w/ 2RP method, the high‑dose range V105% of the target decreased to 0%, and skin adverse events were decreased in conjunction. For patients with early‑stage breast cancer, particularly patients with relatively small‑sized breasts, the FIF w/ 2RP method may be an optimal irradiation method

Dose-volume parameters predict radiation pneumonitis after induction chemoradiotherapy followed by surgery for non-small cell lung cancer: a retrospective analysis

BACKGROUND: The relationship between lung dose-volume histogram (DVH) parameters and radiation pneumonitis (RP) associated with induction concurrent chemoradiotherapy (CCRT) followed by surgery in patients with non-small cell lung cancer (NSCLC) is unclear, particularly when concerning irradiation of the whole lung prior to resection. We performed this study to identify factors associated with grade ≥ 2 RP in such patients. METHODS: Patients who received induction CCRT (chemotherapy: cisplatin and docetaxel; radiotherapy: 46 Gy/23 fractions) between May 2003 and May 2017 were reviewed. The mean lung dose (MLD) and the percentage of the lung volume that received ≥5 Gy (V5) and ≥ 20 Gy (V20) were calculated. Factors associated with the development of grade ≥ 2 RP were analyzed. RESULTS: One hundred and eight patients were included in this study, 34 (31.5%) of whom experienced grade ≥ 2 RP. A V20 ≥ 21%, an MLD ≥10 Gy, and a lower lobe tumor location were significant predictors of grade ≥ 2 RP on univariate analysis (p = 0.007, 0.002, and 0.004, respectively). Moreover, an MLD ≥10 Gy and lower lobe location were significant predictors of grade ≥ 2 RP on multivariate analysis (p = 0.026 and 0.0043, respectively). The cumulative incidence rates of grade ≥ 2 RP at 6 months were 15.7 and 45.6% in patients with MLDs CONCLUSIONS: MLD and lower lobe location were predictors of grade ≥ 2 RP in patients who received induction CCRT. It is necessary to reduce the MLD to the greatest extent possible to prevent the occurrence of this adverse event

Investigation into the Effect of Breast Volume on Irradiation Dose Distribution in Asian Women with Breast Cancer

Reports on irradiation dose distribution in breast cancer radiotherapy with sufficient sample size are limited in Asian patients. Elucidating dose distribution in Asian patients is particularly important as their breast volume differs compared to patients in Europe and North America. Here, we examined dose distribution in the irradiation field relative to breast volume for three irradiation methods historically used in our facility. We investigated the influence of breast volume on each irradiation method for Asian women. A total of 573 women with early-stage breast cancer were treated with breast-conserving surgery and adjuvant radiotherapy. Three methods were compared: wedge (W), field-in-field (FIF), and wedge-field-in-field (W-FIF). In patients with small breast volume, FIF decreased low- and high-dose areas within the planning target volume, and increased optimal dose area more than W. In patients with medium and large breast volumes, FIF decreased high-dose area more than W. The absolute values of correlation coefficients of breast volume to low-, optimal-, and high-dose areas and mean dose were significantly lower in FIF than in W. The correlation coefficients of V107% were 0.00 and 0.28 for FIF and W, respectively. FIF is an excellent irradiation method that is less affected by breast volume than W in Asian breast cancer patients