Nam Kwon Lee

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.

The role of postmastectomy radiation therapy after neoadjuvant chemotherapy in clinical stage II-III breast cancer patients with pN0: A multicenter, retrospective study (KROG 12-05)

PURPOSE The purpose of this study was to investigate the role of postmastectomy radiation therapy (PMRT) after neoadjuvant chemotherapy (NAC) in clinical stage II-III breast cancer patients with pN0. METHODS AND MATERIALS We retrospectively identified 417 clinical stage II-III breast cancer patients who achieved an ypN0 at surgery after receiving NAC between 1998 and 2009. Of these, 151 patients underwent mastectomy after NAC. The effect of PMRT on disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), and overall survival (OS) was evaluated by multivariate analysis including known prognostic factors using the Kaplan-Meier method and compared using the log-rank test and Cox proportional regression analysis. RESULTS Of the 151 patients who underwent mastectomy, 105 (69.5%) received PMRT and 46 patients (30.5%) did not. At a median follow-up of 59 months, 5 patients (3.3%) developed LRR (8 sites of recurrence) and 14 patients (9.3%) developed distant metastasis. The 5-year DFS, LRRFS, and OS rates were 91.2, 98.1, and 93.3% with PMRT and 83.0%, 92.3%, and 89.9% without PMRT, respectively (all P values not significant). By univariate analysis, only age (≤40 vs >40 years) was significantly associated with decreased DFS (P=.027). By multivariate analysis, age (≤40 vs >40 years) and pathologic T stage (0-is vs 1 vs 2-4) were significant prognostic factors affecting DFS (hazard ratio [HR] 0.353, 95% confidence interval [CI] 0.135-0.928, P=.035; HR 2.223, 95% CI 1.074-4.604, P=.031, respectively). PMRT showed no correlation with a difference in DFS, LRRFS, or OS by multivariate analysis. CONCLUSIONS PMRT might not be necessary for pN0 patients after NAC, regardless of clinical stage. Prospective randomized clinical trial data are needed to assess whether PMRT can be safely omitted in pN0 patients after NAC and mastectomy for clinical stage II-III breast cancer.

A Model to Estimate the Risk of Breast Cancer-Related Lymphedema: Combinations of Treatment-Related Factors of the Number of Dissected Axillary Nodes, Adjuvant Chemotherapy, and Radiation Therapy

PURPOSE The development of breast cancer-related lymphedema (LE) is closely related to the number of dissected axillary lymph nodes (N-ALNs), chemotherapy, and radiation therapy. In this study, we attempted to estimate the risk of LE based on combinations of these treatment-related factors. METHODS AND MATERIALS A total of 772 patients with breast cancer, who underwent primary surgery with axillary lymph node dissection from 2004 to 2009, were retrospectively analyzed. Adjuvant chemotherapy (ACT) was performed in 677 patients (88%). Among patients who received radiation therapy (n=675), 274 (35%) received supraclavicular radiation therapy (SCRT). RESULTS At a median follow-up of 5.1 years (range, 3.0-8.3 years), 127 patients had developed LE. The overall 5-year cumulative incidence of LE was 17%. Among the 127 affected patients, LE occurred within 2 years after surgery in 97 (76%) and within 3 years in 115 (91%) patients. Multivariate analysis showed that N-ALN (hazard ratio [HR], 2.81; P<.001), ACT (HR, 4.14; P=.048), and SCRT (HR, 3.24; P<.001) were independent risk factors for LE. The total number of risk factors correlated well with the incidence of LE. Patients with no risk or 1 risk factor showed a significantly lower 5-year probability of LE (3%) than patients with 2 (19%) or 3 risk factors (38%) (P<.001). CONCLUSIONS The risk factors associated with LE were N-ALN, ACT, and SCRT. A simple model using combinations of these factors may help clinicians predict the risk of LE.

Clinical Outcomes of Local Excision Following Preoperative Chemoradiotherapy for Locally Advanced Rectal Cancer

Purpose To evaluate the treatment outcomes of local excision following preoperative chemoradiotherapy in patients with locally advanced rectal cancer who have not undergone radical surgery for any reason. Materials and Methods The data of 27 patients with locally advanced rectal cancer who underwent preoperative chemoradiotherapy followed by local excision were analyzed retrospectively. The primary endpoint was the 5-year relapse-free survival rate, and the secondary endpoint was the pattern of recurrence. Results The median follow-up time was 81.8 months (range, 28.6 to 138.5 months). The 5-year local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), relapse-free survival (RFS), and overall survival (OS) were 88.9%, 81.1%, 77.8%, and 85.0%, respectively. Six (22%) patients developed treatment failure; one (4%) patient had local recurrence only, three (11%) patients had distant recurrence only, and two (7%) patients had both. The 5-year LRFS, DMFS, RFS, and OS for patients with ypT0-1 compared with ypT2-3 were 94.1% vs. 77.8% (p=0.244), 94.1% vs. 55.6% (p=0.016), 88.2% vs. 55.6% (p=0.051), and 94.1% vs. 66.7% (p=0.073), respectively. Conclusion Local excision following preoperative chemoradiotherapy may be an alternative treatment for highly selected patients with locally advanced rectal cancer who have achieved ypT0-1 after preoperative chemoradiotherapy.

Sequential chemotherapy followed by radiotherapy versus concurrent chemoradiotherapy in patients with stage I/II extranodal natural killer/T-cell lymphoma, nasal type

Background The purpose of this report is to summarize our clinical experience of patients with stage I/II extranodal natural killer (NK)/T-cell lymphoma, nasal type, treated using sequential chemotherapy followed by radiotherapy (SCRT) or concurrent chemoradiotherapy (CCRT). Methods Forty-three patients with stage I/II extranodal NK/T-cell lymphoma, nasal type, who received SCRT (16 patients) or CCRT (27 patients) were included in the present analysis. Results The median follow-up time was 39 months (range, 4-171 months) for all patients, 77 months (range, 4-171 months) for the SCRT group, and 31 months (range, 6-132 months) for the CCRT group. There were no statistically significant differences between the SCRT and CCRT groups with regard to the 3-year progression-free survival (PFS) (56% vs. 41%, P=0.823) and 3-year overall survival (OS) (75% vs. 59%, P=0.670). Univariate analysis revealed that patients with tumors confined to the nasal cavity and patients achieved complete remission had better PFS and OS rates, regardless of the treatment sequence. Multivariate analysis revealed that patients with tumors confined to the nasal cavity and patients aged ≤60 years had better OS rates. Conclusion The effect of SCRT and CCRT are similar in terms of survival outcomes of patients with stage I/II extranodal NK/T-cell lymphoma, nasal type. Our results show that tumors confined to the nasal cavity and an age ≤60 years were associated with a better prognosis.

Is elective nodal irradiation beneficial in patients with pathologically negative lymph nodes after neoadjuvant chemotherapy and breast-conserving surgery for clinical stage II–III breast cancer? A multicentre retrospective study (KROG 12-05)

Background:To evaluate the effects of elective nodal irradiation (ENI) in clinical stage II–III breast cancer patients with pathologically negative lymph nodes (LNs) (ypN0) after neoadjuvant chemotherapy (NAC) followed by breast-conserving surgery (BCS) and radiotherapy (RT).Methods:We retrospectively analysed 260 patients with ypN0 who received NAC followed by BCS and RT. Elective nodal irradiation was delivered to 136 (52.3%) patients. The effects of ENI on survival outcomes were evaluated.Results:After a median follow-up period of 66.2 months (range, 15.6–127.4 months), 26 patients (10.0%) developed disease recurrence. The 5-year locoregional recurrence-free survival and disease-free survival (DFS) for all patients were 95.5% and 90.5%, respectively. Pathologic T classification (0−is vs 1 vs 2–4) and the number of LNs sampled (<13 vs ⩾13) were associated with DFS (P=0.0086 and 0.0012, respectively). There was no significant difference in survival outcomes according to ENI. Elective nodal irradiation also did not affect survival outcomes in any of the subgroups according to pathologic T classification or the number of LNs sampled.Conclusions:ENI may be omitted in patients with ypN0 breast cancer after NAC and BCS. But until the results of the randomised trials are available, patients should be put on these trials.

Prophylactic supraclavicular radiotherapy after surgery in high-risk n1 breast cancer.

Objectives: To evaluate the role of prophylactic supraclavicular radiotherapy (RT) by comparing the clinical outcomes of locoregional recurrence (LRR) in high-risk N1 breast cancer. Methods: We performed a retrospective comparison study of 250 high-risk N1 breast cancer patients treated at two institutions. Patients were considered to be high-risk when they had more than two of the following risk factors: lymphovascular invasion, extracapsular extension, metastasis to more than two axillary lymph nodes (ALNs), or level II or higher ALN metastasis. We compared two groups treated with different adjuvant RT fields for the purpose of prophylactic supraclavicular RT (SCRT). Results: Among the 250 patients, 97 patients received SCRT while 153 did not. During follow-up, 32 patients (7 in the SCRT and 25 in the no-SCRT group) had recurrence, and LRR developed in 19 patients, 18 of whom had not received SCRT. In multivariate analysis, SCRT [hazard ratio (HR) 0.072; p = 0.011] and chemotherapy regimen (cyclophosphamide, Adriamycin, and taxane; TAC) were the significant prognostic factors in LRR-free survival (HR 0.385; p = 0.046), and chemotherapy regimen also showed significance for distant metastasis-free survival (HR 0.399; p = 0.037). Conclusions: Use of prophylactic SCRT may reduce the risk of LRR in patients with high-risk N1 breast cancer.

The Role of Adjuvant Radiation Therapy for Locoregionally Advanced Papillary Thyroid Carcinoma

Objectives: To investigate the role of adjuvant radiation therapy in locoregional control in patients with locoregionally advanced papillary thyroid carcinoma (pT4 or pN1b) based on a comparison of a group that received radiation therapy and a group that did not receive radiation therapy. Methods: A retrospective analysis was performed on 165 patients with locoregionally advanced papillary thyroid carcinoma who underwent treatment between 2002 and 2011. Of these, 32 patients received adjuvant radiation therapy, and 133 patients did not receive radiation therapy. Results: The median follow-up period was 7.2 years (range, 3.4-13.6) for the overall study population. The 10-year locoregional recurrence-free survival rates for patients in the radiation therapy and no radiation therapy groups were 83.9 and 60.8%, respectively (p = 0.037). The overall survival rate and distant recurrence-free survival rate were not different between the two groups (p = 0.076 and p = 0.813, respectively). Multivariate analysis showed that adjuvant radiation therapy was an independent prognostic factor for locoregional recurrence-free survival (p = 0.040). Conclusions: Adjuvant radiation therapy for patients with either pT4 or pN1b disease improved locoregional recurrence-free survival and might be of benefit for patients with these high-risk features by reducing the need for additional salvage treatment after locoregional recurrence.

Development of a 3D optical scanner for evaluating patient-specific dose distributions.

PURPOSE This paper describes the hardware and software characteristics of a 3D optical scanner (P3DS) developed in-house. The P3DS consists of an LED light source, diffuse screen, step motor, CCD camera, and scanner management software with 3D reconstructed software. MATERIALS AND METHOD We performed optical simulation, 2D and 3D reconstruction image testing, and pre-clinical testing for the P3DS. We developed the optical scanner with three key characteristics in mind. First, we developed a continuous scanning method to expand possible clinical applications. Second, we manufactured a collimator to improve image quality by reducing scattering from the light source. Third, we developed an optical scanner with changeable camera positioning to enable acquisition of optimal images according to the size of the gel dosimeter. RESULTS We confirmed ray-tracing in P3DS with optic simulation and found that 2D projection and 3D reconstructed images were qualitatively similar to the phantom images. For pre-clinical tests, the dose distribution and profile showed good agreement among RTP, optical CT, and external beam radiotherapy film data for the axial and coronal views. The P3DS has shown that it can scan and reconstruct for evaluation of the gel dosimeter within 1 min. We confirmed that the P3DS system is a useful tool for the measurement of 3D dose distributions for 3D radiation therapy QA. Further experiments are needed to investigate quantitative analysis for 3D dose distribution.

Prognostic value of gross tumor volume for definitive radiation therapy in patients with locoregionally recurrent non-small-cell lung cancer after surgical resection.

PURPOSE To investigate the prognostic value of gross tumor volume (GTV) for predicting survival outcomes and to present the results of definitive radiation therapy (RT) in patients with postsurgical locoregionally recurrent non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS Between April 2001 and September 2009, 38 patients with postsurgical locoregionally recurrent NSCLC underwent definitive RT with curative intent. Median follow-up time for surviving patients was 54.9 months. The primary endpoint was postrecurrence overall survival (OS). The effect of tumor volume on clinical outcome was assessed by using 2 cutoff values of GTV, 20 and 80 cm(3). RESULTS Median postrecurrence survival time was 27.9 months, and the 2-, 3-, and 5-year estimated OS rates were 56.0%, 39.8% and 33.2%, respectively. The median GTV was 26.8 cm(3). Patients with a GTV <20 cm(3) had significantly higher 2-year (69.0% vs. 28.6%) and 3-year (61.4% vs. 14.3%) OS rates than patients with a GTV ≥80 cm(3) (P = .004). Patients with isolated local or regional recurrence had significantly better OS than patients with combined local and regional recurrence (P = .001). Multivariate analysis showed that smaller GTV and isolated local or regional recurrence were independent favorable prognostic factors for OS. CONCLUSIONS Postrecurrence OS of patients with postsurgical locoregionally recurrent NSCLC treated with definitive RT was excellent compared with previous findings. The GTV as a continuous variable was a better predictor of OS than stage at recurrence and may be useful for stratifying the risk in patients with postsurgical recurrent NSCLC.