Heunglae Cho

Analysis of Biologically Equivalent Dose of Stereotactic Body Radiotherapy for Primary and Metastatic Lung Tumors

Purpose The purpose of this study was to determine the optimal biologically equivalent dose (BED) for stereotactic body radiotherapy (SBRT) by comparing local control rates in proportion to various total doses and fractionation schedules. Materials and Methods Thirty-four patients with early non-small-cell lung cancer and a single metastatic lung tumor were included in this study. Differences in local control rates were evaluated according to gender, primary tumor site, response, tumor size, and BED. For comparison of BEDs, the prescribed dose for SBRT was stratified according to three groups: high (BED > 146 Gy), medium to high (BED, 106 to 146 Gy), and low to medium (BED < 106 Gy). Results For all patients, the overall local control rate was 85.3% at two years after treatment. Five local recurrences were observed, and, notably, all of them were observed in the low to medium BED group. Significantly higher local control rates were observed for patients with a complete response than for those with a partial response or stable disease (p < 0.001). Twenty-six patients with a tumor size of < 3 cm showed no dose-response relationship in the low to medium, medium to high, and high BED groups, whereas eight patients with a tumor size of ≥ 3 cm showed a significant dose-response relationship. The observed 2-year local recurrence-free survival rates in patients with a tumor size of < 3 cm and in those with a tumor size of ≥ 3 cm were 96.2% and 50.0%, respectively, which were significantly different (p=0.007). Conclusion BED > 100 Gy is required in order to achieve a > 85% local control rate regardless of tumor size. The optimal dose for small tumors of < 3 cm appears to be within a range below 150 Gy BED. Escalation of BED to high levels (> 150 Gy) may be required for patients with a tumor size larger than 3 cm.

The Effect of Probiotics for Preventing Radiation-Induced Morphological Changes in Intestinal Mucosa of Rats

Radiation therapy is an important treatment modality for abdominal or pelvic cancer, but there is a common and serious complication such as radiation-induced enteritis. Probiotics is reported to have positive effects against radiation-induced enteropathy. In this study, morphological changes of bowel mucosa were analyzed in rats to presume the effect of probiotics on radiation-induced enteritis and its correlation with radiation dose. A total of 48 adult male Sprague-Dawley rats were randomly assigned to two groups and received a solution containing 1.0×108 colony-forming units of Lactiobacillus acidophilus or water once daily for 10 days. Each of two groups was divided into three subgroups and abdomino-pelvic area of each subgroup was irradiated with 10, 15, and 20 Gy, respectively on the seventh day of feeding the solutions. All rats were sacrificed 3 days after irradiation and the mucosal thickness and villus height of jejunum, ileum and colon were measured. The morphological parameters of the small intestine represented significant differences between two solution groups irradiated 10 or 15 Gy, except for villus height of jejunum in 15 Gy-subgroup (P=0.065). There was no significant morphometric difference between two groups irradiated with 20 Gy of radiation. Probiotics appear to be effective for the morphological shortening of small intestinal mucosa damaged by radiation less than or equal to 15 Gy. Graphical Abstract

Volumetric changes in the lumpectomy cavity during whole breast irradiation after breast conserving surgery

Purpose This study was performed to evaluate the change in the lumpectomy cavity volumes before and after whole breast radiation therapy (WBRT) and to identify factors associated with the change of volume. Materials and Methods From September 2009 to April 2010, the computed tomography (CT) simulation data from 70 patients obtained before and after WBRT was evaluated. The lumpectomy cavity volumes were contoured based on surgical clips, seroma, and postoperative changes. Significant differences in the data from pre-WBRT CT and post-WBRT CT were assessed. Multiple variables were examined for correlation with volume reduction in the lumpectomy cavity. Results The mean and median volume reduction in the lumpectomy cavity after WBRT were 17.6 cm3 and 16.1 cm3, respectively with the statistical significance (p < 0.001). The volume reduction in the lumpectomy cavity was inversely correlated with time from surgery to radiation therapy (R = 0.390). The presence of seroma was significantly associated with a volumetric change in the lumpectomy cavity after WBRT (p = 0.011). Conclusion The volume of lumpectomy cavity reduced significantly after WBRT. As the time from surgery to the start of WBRT increased, the volume reduction in the lumpectomy cavity during WBRT decreased. A strong correlation was observed between the presence of seroma and the reduced volume. To ensure appropriate coverage and to limit normal tissue exposure during boost irradiation in patients who has seroma at the time of starting WBRT, repeating CT simulation at boost planning is suggested.

The Suitability of Absorbable Mesh Insertion for Oncoplastic Breast Surgery in Patients with Breast Cancer Scheduled to Be Irradiated

Purpose The objective of this study was to investigate the influence of radiotherapy on the cosmetic outcome after immediate breast reconstruction using an absorbable mesh in breast cancer. Methods From July 2008 to July 2009, 35 breast cancer patients who received immediate breast reconstruction with absorbable mesh insertion at the time of breast conserving surgery followed by radiotherapy were retrospectively studied. Results In 91% of cases there was an excellent or good cosmetic outcome before the initiation of radiotherapy, and in 8.6% the outcome was fair at this point. However, 6 months after surgery and irradiation, the rate of excellent to good cosmetic outcomes had decreased to 60% and fair outcomes had increased to 25.7%. Contrary to the decreased rate of good cosmetic outcomes from 65.7% to 42.9% at 1 year after operation, the rate of fair to poor outcomes considerably increased from 8.6% to 57.1%. The significant factors affecting cosmetic outcomes were pathology, specimen volume, and the estimated percentage of breast volume excised (EPBVE). Chemotherapy affected the cosmetic outcome at borderline significance level. Age, breast volume tumor site, insertion of drain, radiation dose, and time elapsed between surgery and radiotherapy were not significantly associated with the cosmetic outcome. Conclusion Applying an absorbable mesh for the immediate reconstruction of the breast should be carefully considered in patients with an EPBVE of over 30% who are scheduled to be irradiated.

Eribulin Mesylate Combined with Local Treatment for Brain Metastasis from Breast Cancer: Two Case Reports

The prognosis associated with brain metastasis arising from breast cancer is very poor. Eribulin is a microtubule dynamic inhibitor synthesized from halichondrin B, a natural marine product. In a phase III study (EMBRACE), eribulin improved overall survival in patients with heavily pretreated metastatic breast cancers. However, these studies included few patients with brain metastases. Metastatic brain tumors (MBT) were detected during first-line palliative chemotherapy in a 43-year-old woman with breast cancer metastasis to the lung and mediastinal nodes; the genetic subtype was luminal B-like human epidermal growth factor receptor 2 (HER2)-negative. Whole brain radiotherapy (WBRT) followed by eribulin treatment continuously decreased the size, and induced regression, of the MBT with systemic disease stability for 12 months. Another 48-year-old woman with metastatic breast cancer (HER2+ subtype) presented with MBT. Following surgical resection of the tumor, eribulin with concurrent WBRT showed regression of the MBT without systemic progression for 18 months.

Addition of Anti-neu Antibody to Local Irradiation Can Improve Tumor- Bearing BALB/c Mouse Survival through Immune-Mediated Mechanisms

This study investigated the therapeutic effects of combined local irradiation and anti-HER2/neu antibody in a mixed tumor mouse model comprised of a nonmetastatic neu-positive tumor and a metastatic neu-negative tumor. While local irradiation alone could control the primary tumor in a dose-dependent manner, it did not improve mouse survival. Combined treatment comprised of local irradiation and anti-neu antibody of tumor-bearing BALB/c mice significantly improved mouse survival (P < 0.5), even though the tumor growth was similar to that of the irradiated-alone group. The combined treatment significantly reduced metastatic tumor masses in the lung and increased immune cell infiltration in primary tumor tissues. However, immune deficient nude mice with tumors did not exhibit prolonged survival in response to the combined treatment. Collectively, these results show that combined local irradiation and anti-neu antibody can elicit an immune-mediated abscopal effect to extend survival. Although the mechanism for abscopal effects induced by the combined treatment of radiation and anti-HER2/neu antibody was not elucidated, to our knowledge this is the first published study to describe the abscopal effect induced by the combination of local irradiation and the anti-HER2/neu antibody.

Association between obesity and local control of advanced rectal cancer after combined surgery and radiotherapy.

Purpose: The association between metabolism and cancer has been recently emphasized. This study aimed to find the prognostic significance of obesity in advanced stage rectal cancer patients treated with surgery and radiotherapy (RT). Materials and Methods: We retrospectively reviewed the medical records of 111 patients who were treated with combined surgery and RT for clinical stage 2–3 (T3 or N+) rectal cancer between 2008 and 2014. The prognostic significance of obesity (body mass index [BMI] ≥25 kg/m2) in local control was evaluated. Results: The median follow-up was 31.2 months (range, 4.1 to 85.7 months). Twenty-five patients (22.5%) were classified as obese. Treatment failure occurred in 33 patients (29.7%), including local failures in 13 patients (11.7%), regional lymph node failures in 5, and distant metastases in 24. The 3-year local control, recurrence-free survival, and overall survival rates were 88.7%, 73.6%, and 87.7%, respectively. Obesity (n = 25) significantly reduced the local control rate (p = 0.045; 3-year local control, 76.2%), especially in women (n = 37, p = 0.021). Segregation of local control was best achieved by BMI of 25.6 kg/m2 as a cutoff value. Conclusion: Obese rectal cancer patients showed poor local control after combined surgery and RT. More effective local treatment strategies for obese patients are warranted.

Being Overweight or Obese Increases the Risk of Progression in Triple-Negative Breast Cancer after Surgical Resection

This study aimed to evaluate the association between body mass index (BMI) and progression in triple-negative breast cancer (TNBC). We retrospectively reviewed the medical records of 50 patients with TNBC who underwent breast-conserving surgery or mastectomy between 2007 and 2014. All patients were classified according to BMI (median 23.5 kg/m2, range 17.2–31.6 kg/m2): 31 patients (62%) were classified as being overweight or obese (BMI ≥ 23 kg/m2) and 19 patients (38%) were classified as having a normal body weight (BMI < 23 kg/m2). The median follow-up for patients was 31.1 months (range, 6.7–101.9 months). Progression occurred in 7 patients (14%), including 5 ipsilateral breast tumor recurrences, 2 regional lymph node metastases, and 5 distant metastases. Progression was significantly correlated with overweight or obese patients (P = 0.035), while none of the normal weight patients showed progression. The 3-year disease-free survival (DFS) and overall survival (OS) rates were 85.0% and 87.7%, respectively. DFS was significantly reduced in overweight or obese patients compared to that in normal weight patients (P = 0.035). However, OS was not significantly compromised by being overweight or obese (P = 0.134). In conclusion, being overweight or obese negatively affects DFS in TNBC patients.

Study on the feasibility of the HgI2 dosimeter for quality assurance of radiotherapy

In radiotherapy, a variety of detectors such as ionization chambers, films, TLDs, diodes, and OSL, are being used for quality assurance (QA). Owing to its high sensitivity and feasibility to operate at low voltages, silicon (Si) photoconductors, which are used as detection material of a diode, are currently being used as relative dosimeters. In addition, other materials such as amorphous selenium (a-Se), cadmium telluride (CdTe), lead iodide (PbI2), and mercury iodide (HgI2) were also being investigated for their feasibility as diagnostic radiation detector. Among these materials, HgI2 has been reported to show remarkable properties including high spatial resolution and high stopping power. Hence In this study, we have verified the feasibility of HgI2 dosimeter for quality assurance of radiotherapy. In order to fabricate the detector, HgI2 was mixed with TiO2 to minimize the signal reduction. Following this, the resulting mixture was deposited onto indium tin oxide (ITO) coated glass by particle-in binder (PIB) method. Finally, the top ITO electrode was coated by magnetron sputterring system. Subsequently, we measured the electrical properties generated by high-energy radiation from linear accelerator (LINAC), and analyzed the reproducibility, linearity, and percent depth dose (PDD) of the fabricated detoctor. In addition, we have determined the build-up materials in experimental setup, since the thickness of build-up region, where the secondary electron emission equilibrium occurs, changes depending on radiation energy. It was observed that the relative variations measured as standard deviation divided by the average value among repeated measurements was approximately 1%. Deviations from linearity are smaller than 5%. Finally, we compared the experimental data of the detector fabricated in this study with those of the farmer-type ionization chamber. Base on the results obtained from this study, it could be realized that HgI2 could be used as dosimeter for QA of radiotherapy.

Efficacy of Dose-Escalated Radiotherapy for Recurrent Colorectal Cancer.

Purpose This study aimed to evaluate the effects of radiotherapy (RT) on progression-free survival (PFS) for patients with recurrent colorectal cancer. Methods We reviewed the records of 22 patients with recurrent colorectal cancer treated with RT between 2008 and 2014. The median radiation dose for recurrent disease was 57.6 Gy (range, 45–75.6 Gy). Patients were divided into 2 groups according to the type of RT: patients underwent RT without previous history of irradiation (n = 14) and those treated with secondary RT (reirradiation: n = 8) at the time of recurrence. Results The median follow-up period was 24.9 months (range, 4.5–66.6 months). Progression was observed in 14 patients (including 8 with loco-regional failure and 9 with distant metastases). Distant metastases were related to the RT dose (<70 Gy, P = 0.031). The 2-year loco-regional control (LRC), PFS, and overall survival (OS) rates were 74.6%, 45.1%, and 82.0%, respectively. The LRC rate was not different between the patients treated with RT for the first time and those treated with reirradiation (P = 0.101, 2-year LRC 79.5% vs. 41.7%). However, reirradiation was related to poor PFS (P = 0.022) and OS (P = 0.002). An escalated RT dose (≥70 Gy) was associated with a higher PFS (P = 0.014, 2-year PFS 63.5% vs. 20.8%). Conclusion Salvage RT for locally recurrent colorectal cancer can be offered when surgery is impossible. Dose-escalated RT shows a possible benefit in reducing the risk of progression.