Ja Young Kim

Phase II trial of proton beam accelerated partial breast irradiation in breast cancer

BACKGROUND AND PURPOSE Here, we report the results of our phase II, prospective study of proton beam accelerated partial breast irradiation (PB-APBI) in patients with breast cancer after breast conserving surgery (BCS). MATERIALS AND METHODS Thirty patients diagnosed with breast cancer were treated with PB-APBI using a single-field proton beam or two fields after BCS. The treatment dose was 30 cobalt gray equivalent (CGE) in six CGE fractions delivered once daily over five consecutive working days. RESULTS All patients completed PB-APBI. The median follow-up time was 59 months (range: 43-70 months). Of the 30 patients, none had ipsilateral breast recurrence or regional or distant metastasis, and all were alive at the last follow-up. Physician-evaluated toxicities were mild to moderate, except in one patient who had severe wet desquamation at 2 months that was not observed beyond 6 months. Qualitative physician cosmetic assessments of good or excellent were noted in 83% and 80% of the patients at the end of PB-APBI and at 2 months, respectively, and decreased to 69% at 3 years. A good or excellent cosmetic outcome was noted in all patients treated with a two-field proton beam at any follow-up time point except for one. For all patients, the mean percentage breast retraction assessment (pBRA) value increased significantly during the follow-up period (p=0.02); however, it did not increase in patients treated with two-field PB-APBI (p=0.3). CONCLUSIONS PB-APBI consisting of 30 CGE in six CGE fractions once daily for five consecutive days can be delivered with excellent disease control and tolerable skin toxicity to properly selected patients with early-stage breast cancer. Multiple-field PB-APBI may achieve a high rate of good-to-excellent cosmetic outcomes. Additional clinical trials with larger patient groups are needed.

Diagnostic Value of Neck Node Status Using 18F-FDG PET for Salivary Duct Carcinoma of the Major Salivary Glands

18F-FDG PET and PET/CT have shown clinical usefulness in the initial staging and follow-up of patients with salivary malignancy. Therefore, we evaluated the utility of 18F-FDG PET in preoperative staging, determining the extent of neck node involvement, and surgical planning for patients with salivary duct carcinoma (SDC) of the major salivary gland. Methods: We evaluated 18 patients with SDC who were assessed by 18F-FDG PET and CT before surgery. The sensitivity, specificity, accuracy, and predictive values of CT and PET/CT for predicting the primary tumor site and determining the extent of neck node involvement at each dissected neck level were evaluated by comparing imaging findings with pathologic nodal stage. Results: The median maximum standardized uptake value of the primary lesions and cervical nodes were 4.7 (range, 1.8–12.1) and 5.8 (range, 1.7–13.0), respectively. The sensitivities of 18F-FDG PET and CT for predicting the primary tumor site were 100% (18/18) and 94.4% (17/18), respectively. In analyzing cervical lymph nodes at 73 dissected neck levels, 18F-FDG PET had a sensitivity of 76.1%, a specificity of 96.3%, a positive predictive value of 97.2%, and a negative predictive value of 70.3%; the corresponding values for CT were 39.1%, 92.6%, 90.0%, and 47.2%, respectively. The sensitivity and negative predictive value were significantly higher for 18F-FDG PET than for CT (P < 0.001 and P = 0.03, respectively).18F-FDG PET determination of the extent of neck node involvement changed the neck dissection regimen in 5 patients (27.8%). Conclusion: SDC of the major salivary gland is a highly metabolic tumor with high 18F-FDG uptake. 18F-FDG PET is useful for evaluating neck node status and for determining surgical planning in patients with major salivary gland SDC.

Normal liver sparing by proton beam therapy for hepatocellular carcinoma: Comparison with helical intensity modulated radiotherapy and volumetric modulated arc therapy

To the Editor, Technical advances in radiotherapy (RT) planning systems using computed tomography (CT), such as three-dimensional conformal RT (3D-CRT), along with greater understanding of partial liver tolerance have increased the use of RT in the non-surgical management of patients with hepatocellular carcinoma (HCC) [1]. Radiation-induced liver disease (RILD) is one of the most common dose limiting toxicities in patients receiving RT for HCC. While most cases of RILD are self-limiting and manageable with supportive care, this complication may result in the deterioration of hepatic reserve, with severe injury resulting in liver failure and death. Therefore, when treating HCC patients with RT, it is important not only to maximize the effective dose delivered to the tumor but to minimize the dose delivered to the surrounding normal liver. Intensity-modulated radiotherapy (IMRT), using intensity-modulated beams to deliver a high dose to the tumor while reducing the dose to the surrounding normal tissues, and image-guided RT (IGRT) have been available. Recently, the more sophisticated RT techniques, such as helical-IMRT (H-IMRT), a type of fusion technology that combines IMRT and IGRT, and volumetric modulated arc therapy (VMAT), which uses modulated treatment apertures [defi ned by dynamic multi-leaf collimator (MLC)] and dose rate, have been shown to provide equal or better tumor coverage and better sparing of normal tissues than 3D-CRT and/or IMRT in patients with HCC [2 – 7]. Proton beam therapy (PBT) is another promising treatment option that can deliver a high radiation dose to the tumor while minimizing the radiation dose delivered to the remaining normal liver due to the unique characteristics of proton beams, the Bragg peak, allowing deposition of high doses of radiation within the target, with much lower doses outside the target. However, despite the conceptual benefi ts and promising clinical outcomes of PBT [8 – 13], it is remained unclear whether PBT is benefi cial in reducing the irradiated liver volume comparing with aforementioned more sophisticated RT techniques or not. Therefore, this study was designed to compare the effects of PBT, H-IMRT, and VMAT on irradiated liver volume in patients with HCC.

Phase 2 trial of accelerated, hypofractionated whole-breast irradiation of 39 Gy in 13 fractions followed by a tumor bed boost sequentially delivering 9 Gy in 3 fractions in early-stage breast cancer.

PURPOSE To report a phase 2 trial of accelerated, hypofractionated whole-breast irradiation (AH-WBI) delivered as a daily dose of 3 Gy to the whole breast followed by a tumor bed boost. METHODS AND MATERIALS Two hundred seventy-six patients diagnosed with breast cancer (pT1-2 and pN0-1a) who had undergone breast-conserving surgery in which the operative margins were negative were treated with AH-WBI delivered as 39 Gy in 13 fractions of 3 Gy to the whole breast once daily over 5 consecutive working days, and 9 Gy in 3 sequential fractions of 3 Gy to a lumpectomy cavity, all within 3.2 weeks. RESULTS After a median follow-up period of 57 months (range: 27-75 months), the rate of 5-year locoregional recurrence was 1.4% (n=4), whereas that of disease-free survival was 97.4%. No grade 3 skin toxicity was reported during the follow-up period. Qualitative physician cosmetic assessments of good or excellent were noted in 82% of the patients at 2 months after the completion of AH-WBI. The global cosmetic outcome did not worsen over time, and a good or excellent cosmetic outcome was reported in 82% of the patients at 3 years. The mean pretreatment percentage breast retraction assessment was 12.00 (95% confidence interval [CI]: 11.14-12.86). The mean value of percentage breast retraction assessment increased to 13.99 (95% CI: 12.17-15.96) after 1 year and decreased to 13.54 (95% CI: 11.84-15.46) after 3 years but was not significant (P>.05). CONCLUSIONS AH-WBI consisting of 39 Gy in 13 fractions followed by a tumor bed boost sequentially delivering 9 Gy in 3 fractions can be delivered with excellent disease control and tolerable skin toxicity in patients with early-stage breast cancer after breast-conserving surgery.

Disease courses in patients with residual tumor following concurrent chemoradiotherapy for locally advanced cervical cancer

OBJECTIVE To investigate the disease course and identify prognostic factors for survival in patients with residual disease according to post-treatment magnetic resonance imaging (MRI) following definitive concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer. METHODS We reviewed clinical data from the medical records of 545 consecutive women with biopsy-proven, International Federation of Gynecology and Obstetrics stage IB2-IVA uterine cervical cancer treated with CCRT. Post-treatment MRI was checked in all patients 3months after CCRT completion. Out of the 545 patients, 53 with residual cervical cancer based on MRI following definitive CCRT were included in this analysis. RESULTS Thirty-two patients were disease-free at the last follow-up. Of them, 31 had a residual tumor size of ≤2cm. Of these 32 women, 30 showed spontaneous regression of residual tumor during follow-up without salvage treatments, whereas the remaining two were alive with no evidence of disease after salvage surgery and chemotherapy. Disease progression was observed in 21 patients, including 7 local, 8 distant and 6 local and distant failures. Of these 21 women, 13 died of disease, 6 were alive with disease, and 2 remained disease-free after salvage treatments. Initial and residual tumor sizes were significant prognostic factors for overall survival; only residual tumor size was significant for local progression-free survival. CONCLUSIONS About 60% of patients with residual disease detected on post-treatment MRI remained disease-free without further disease progression. Careful observation without immediate salvage treatments might be feasible in selected patients with a residual tumor size ≤2cm.

Incorporating Risk Factors to Identify the Indication of Post-mastectomy Radiotherapy in N1 Breast Cancer Treated with Optimal Systemic Therapy: A Multicenter Analysis in Korea (KROG 14-23)

Purpose In a recent meta-analysis, post-mastectomy radiotherapy (PMRT) reduced any first recurrence (AFR) and improved survival in N1 and N2 patients. We investigated risk factors for AFR in N1 after optimal systemic therapy without PMRT, to define a subgroup of patients who may benefit from PMRT. Materials and Methods One thousand three hundred eighty-two pT1-2N1M0 breast cancer patients treated with mastectomy without PMRT between 2005 and 2010 were retrospectively analyzed. Only 0.6% had no systemic therapy. Results After a median follow-up of 5.9 years, there were 173 AFR (53 loco-regional recurrence [LRR] without distant metastases [DM], 38 LRR with DM, and 82 DM without LRR). The 5-year LRR and AFR rates were 6.1% and 12.0%, respectively. Multivariate analysis revealed that close resection margin (p=0.001) was the only independent risk factor for LRR. Multivariate analysis for AFR revealed that age < 35 years (p=0.025), T2 stage (p=0.004), high tumor grade (p=0.032), close resection margin (p=0.035), and triple-negative biological subtype (p=0.031) were independent risk factors. Two or three positive lymph nodes (p=0.078) were considered a marginally significant factor. When stratified by these six factors, the 5-year LRR rates were 3.6% with 0-1 (n=606), 7.5% with 2-3 (n=655), and 12.7% with 4-6 (n=93) risk factors. The 5-year AFR rates were 7.1% with 0-1, 15.0% with 2-3, and 24.5% with 4-6 risk factors. Conclusion Patients with pT1-2N1M0 breast cancer who underwent mastectomy and optimal systemic therapy showed excellent loco-regional control and disease control. The patients with four or more risk factors may benefit from PMRT, and those with two or three risk factors merit consideration of PMRT.

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.

Treatment outcome in patients with triple negative early stage breast cancers compared with other molecular subtypes

Purpose To determine whether triple negative (TN) early stage breast cancers have poorer survival rates compared with other molecular types. Materials and Methods Between August 2000 and July 2006, patients diagnosed with stage I, II early stage breast cancers, in whom all three markers (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor [HER]-2) were available and treated with modified radical mastectomy or breast conserving surgery followed by radiotherapy, were retrospectively reviewed. Results Of 446 patients, 94 (21.1%) were classified as TN, 57 (12.8%) as HER-2 type, and 295 (66.1%) as luminal. TN was more frequently associated with young patients younger than 35 years old (p = 0.002), higher histologic grade (p < 0.0001), and nuclear (p < 0.0001). The median follow-up period was 78 months (range, 4 to 130 months). There were 9 local relapses (2.0%), 15 nodal (3.4%), 40 distant metastases (9.0%), and 33 deaths (7.4%) for all patients. The rates of 5-year OS, DFS, LFS, and DMFS for all patients were 95.5%, 89.9%, 95.4%, and 91.7%, respectively. There were no significant differences in OS, DFS, LFS, and DMFS between triple negative and other subtypes (p > 0.05). Conclusion We found that patients with TN early stage breast cancers had no difference in survival rates compared with other molecular subtypes. Prospective study in homogeneous treatment group will need for a prognosis of TN early stage breast cancer.

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.

Treatment outcomes of curative radiotherapy in patients with vulvar cancer: Results of the retrospective KROG 1203 study

Purpose We evaluated the prognostic factors and clinical outcomes of 56 patients with vulvar cancer treated with curative radiotherapy (RT) or concurrent chemoradiotherapy. Materials and Methods Overall survival (OS) and disease-free survival (DFS) were assessed retrospectively. Prognostic factors evaluated included age, International Federation of Gynecology and Obstetrics (FIGO) stage, TNM classification, tumor size, treatment modality, RT duration, and RT field. The association between the tumor human papillomavirus (HPV) status and survival was analyzed in 35 patients. Results During the median follow-up of 2.8 years (range, 0.3 to 18.9 years), 21 patients (37.5%) experienced treatment failure. Fifteen patients (27%) had local failure: nine (16%) local failure only, three (5%) locoregional failure, two (4%) local and distant failure, and one (2%) locoregional and distant failure. Of 56 patients, seven (13%) had persistent disease at the first follow-up at 2 months and all but one died within a year after completing RT. The 5-year OS and DFS were 51.6% and 44.0%, respectively. In multivariate analysis, clinical size ≥3 cm predicted a poor prognostic factor for DFS (p = 0.040) and age (≥70 years) was poor prognostic for DFS (p = 0.032) and OS (p = 0.048). Patients with HPV-positive tumors tended to have better 5-year OS and DFS, but the differences were not significant statistically. Conclusion Clinical size ≥3 cm was a significant prognostic factor for DFS. However, age was the most important prognostic factor for DFS and OS in patients treated with curative RT. Further studies are needed to determine which treatment should be considered for old age ≥70 years.