Validation of a nomogram for predicting the risk of lymphedema following contemporary treatment for breast cancer: a large multi-institutional study (KROG 20-05).

PURPOSE: We previously constructed a nomogram for predicting the risk of arm lymphedema following contemporary breast cancer treatment. This nomogram should be validated in patients with different background characteristics before use. Therefore, we aimed to externally validate the nomogram in a large multi-institutional cohort. METHODS: Overall, 8835 patients who underwent breast cancer surgery during 2007-2017 were identified. Data of variables in the nomogram and arm lymphedema were collected. The nomogram was validated externally using C-index and integrated area under the curve (iAUC) with 1000 bootstrap samples and by calibration plots. RESULTS: Overall, 1377 patients (15.6%) developed lymphedema. The median time from surgery to lymphedema development was 11.4 months. Lymphedema rates at 2, 3, and 5 years were 11.2%, 13.1%, and 15.6%, respectively. Patients with lymphedema had significantly higher body mass index (median, 24.1 kg/m2 vs. 23.4 kg/m2) and a greater number of removed nodes (median, 17 vs. 6) and more frequently underwent taxane-based chemotherapy (85.7% vs. 41.9%), total mastectomy (73.1% vs. 52.1%), conventionally fractionated radiotherapy (71.9% vs. 54.2%), and regional nodal irradiation (70.7% vs 22.4%) than those who did not develop lymphedema (all P < 0.001). The C-index of the nomogram was 0.7887, and iAUC was 0.7628, indicating good predictive accuracy. Calibration plots confirmed that the predicted lymphedema risks were well correlated with the actual lymphedema rates. CONCLUSION: This nomogram, which was developed using factors related to multimodal breast cancer treatment and was validated in a large multi-institutional cohort, can well predict the risk of breast cancer-related lymphedema.

Central Nervous System Failure in Korean Breast Cancer Patients with HER2-Enriched Subtype: Korean Radiation Oncology Group 16-15 Multicenter Retrospective Study.

PURPOSE: The purpose of this study was to evaluate the risk of central nervous system (CNS) failure in Korean patients with human epidermal growth factor receptor 2 (HER2)-enriched breast cancer treated with surgery followed by postoperative radiotherapy (RT). METHODS: A total of 749 patients from eight institutions were enrolled in this study. All of them underwent surgery followed by postoperative RT from 2003 to 2011; 246 (32.8%) received neoadjuvant chemotherapy and 649 (81.7%) received adjuvant chemotherapy. Adjuvant trastuzumab was administered to 386 patients (48.6%). RESULTS: The median follow-up duration was 84 (range, 8-171) months. The 7-year disease-free and overall survival rates were 79.0% and 84.2%, respectively. On multivariate analysis, mastectomy, nodal involvement, and presence of lymphatic invasion were correlated with poor overall survival (p = 0.004, 0.022, and 0.011, respectively), whereas T stage and lymphatic invasion were associated with disease-free survival (p = 0.018 and 0.005, respectively). Regarding CNS failures, 30 brain metastases, 2 leptomeningeal metastases, and 8 brain and leptomeningeal metastases were noted. The 7-year CNS relapse-free survival rates in patients receiving and not receiving trastuzumab were 91.2% and 96.9%, respectively (p = 0.005). On multivariate analysis, the administration of adjuvant trastuzumab was the only prognostic factor in predicting a higher CNS failure rate (hazard ratio, 2.260; 95% confidence interval, 1.076-4.746; p = 0.031). CONCLUSION: Adjuvant trastuzumab was associated with higher CNS failure rate in Korean patients with HER2-enriched breast cancer. Close monitoring and reasonable approaches such as CNS penetrating HER2 blockades combined with the current standard therapy could contribute to improving intracranial tumor control and quality of life in patients with CNS metastasis from HER2-enriched breast cancer.

Risk factors for distant metastasis as a primary site of treatment failure in early-stage breast cancer.

The aim of this study was to evaluate the risk factors for distant metastasis (DM) as a primary site of failure in early-stage breast cancer. Data from 294 patients diagnosed with pathologic stage I or II breast cancer between January 2000 and December 2005 were reviewed retrospectively. Median follow-up duration was 81.0 months (range, 18-135 months). The total number of patients with DM without evidence of locoregional recurrence was 20 and the median time between surgery and DM was 29 months (range, 9-79 months). Median survival time was 38 months (range, 22-77 months) after operation. HER-2 positivity (p=0.015), T stage of tumor (p=0.012), and number of involved lymph nodes (p=0.008) were significant predictors of DM in the univariable analysis. Number of involved lymph nodes [p=0.005, hazards ratio (HR): 1.741; 95% confidence interval (CI): 1.178-2.574] and HER-2 positivity (p=0.018, HR: 2.888; 95% CI: 1.201-6.941) had a statistically significant effect on DM-free survival in the multivariable analysis. A cautious evaluation may be helpful when patients with risk factors for DM have symptoms implying the possibility of DM. To reduce DM, applying intensive therapy is needed after curative surgery for patients with high risk for DM.

Intensity modulated radiosurgery for the spine: dosimetric impact of beamlet size variation in the leaf travel direction.

BACKGROUND AND PURPOSE: To investigate the dosimetric impact of beamlet size in the leaf travel direction for the spinal treatment using intensity-modulated radiosurgery (IMRS). MATERIALS AND METHODS: The IMRS plans of ten patients (11 lesions - 6 thoracic, 2 cervical, 3 lumbar) were re-planned using four different beamlet sizes (1, 2, 5, and 10 mm) - in the leaf travel direction, while keeping the Y-dimension by multi-leaf collimator (MLC) width fixed, and compared to the reference plan with beamlet size of 3 mm. To evaluate the beamlet size effect, target volumes (coverage, conformity, and size effect), organ at risks (OARS) (doses to the spinal cord, lung and kidneys), and integral dose, and monitor units (MUs) were calculated. RESULTS: Target coverage and dose conformity for planning target volume (PTV) were not correlated with beamlet size. Maximum (p=0.000) and mean (p=0.000) spinal cord doses decreased by 4.0% and 3.4% from 23.4% and 28.6% as beamlet size decreased from 10 to 1 mm. The integral doses, MUs and doses to other organs increased at smaller beamlet sizes. MUs for a beamlet size of 10 mm decreased by 31.4%, as compared with that at the reference beamlet size. CONCLUSIONS: Despite no dosimetric benefits with respect to target volume and an MU increase, a definite dose reduction was observed at the spinal cord for smaller beamlet sizes. Treatment with IMRS planning for the spine will benefit from the use of a beamlet size between 2 and 4 mm.

A comparison of preplan MRI and preplan CT-based prostate volume with intraoperative ultrasound-based prostate volume in real-time permanent brachytherapy.

PURPOSE: The present study compared the difference between intraoperative transrectal ultrasound (iTRUS)-based prostate volume and preplan computed tomography (CT), preplan magnetic resonance imaging (MRI)-based prostate volume to estimate the number of seeds needed for appropriate dose coverage in permanent brachytherapy for prostate cancer. MATERIALS AND METHODS: Between March 2007 and March 2011, among 112 patients who underwent permanent brachytherapy with (125)I, 60 image scans of 56 patients who underwent preplan CT (pCT) or preplan MRI (pMRI) within 2 months before brachytherapy were retrospectively reviewed. Twenty-four cases among 30 cases with pCT and 26 cases among 30 cases with pMRI received neoadjuvant hormone therapy (NHT). In 34 cases, NHT started after acquisition of preplan image. The median duration of NHT after preplan image acquisition was 17 and 21 days for cases with pCT and pMRI, respectively. The prostate volume calculated by different modalities was compared. And retrospective planning with iTRUS image was performed to estimate the number of (125)I seed required to obtain recommended dose distribution according to prostate volume. RESULTS: The mean difference in prostate volume was 9.05 mL between the pCT and iTRUS and 6.84 mL between the pMRI and iTRUS. The prostate volume was roughly overestimated by 1.36 times with pCT and by 1.33 times with pMRI. For 34 cases which received NHT after image acquisition, the prostate volume was roughly overestimated by 1.45 times with pCT and by 1.37 times with pMRI. A statistically significant difference was found between preplan image-based volume and iTRUS-based volume (p < 0.001). The median number of wasted seeds is approximately 13, when the pCT or pMRI volume was accepted without modification to assess the required number of seeds for brachytherapy. CONCLUSION: pCT-based volume and pMRI-based volume tended to overestimate prostate volume in comparison to iTRUS-based volume. To reduce wasted seeds and cost of the brachytherapy, we should take the volume discrepancy into account when we estimate the number of (125)I seeds for permanent brachytherapy.