Design and evaluation of electron beam energy degraders for breast boost irradiation.

BACKGROUND: For breast cancer patients who require electron boost energies between 6 and 9 MeV, an energy degraders (ED) in the 9 MeV beamline was specially designed and manufactured to increase the skin dose of 6 MeV and to reduce the penetration depth of 9 MeV beams. METHODS: We used Monte Carlo (MC) techniques as a guide in the design of ED for use with linear accelerators. In order to satisfy percent depth dose (PDD) characteristics and dose profile uniformity in water, the shape and thickness of Lucite® ED in the 9 MeV beamline was iteratively optimized and then manufactured. The ED geometry consists of a truncated cone attached on top of a plane plate, with total central thickness of 1.0 cm. The ED was placed on the lower most scraper of the electron applicator. The PDDs, profiles, and output factors were measured in water to validate the MC-based design. RESULTS: Skin doses with the EDs increased by 8-9 %, compared to those of the 9 MeV beam. The outputs with the EDs were 0.882 and 0.972 for 10 × 10 and 15 × 15 cm(2) cones, respectively, as compared to that of a conventional 9 MeV beam for a 10 × 10 cm(2) cone. The X-ray contamination remained less than 1.5 %. In-vivo measurements were also performed for three breast boost patients and showed close agreement with expected values. CONCLUSIONS: The optimally designed ED in the 9 MeV beamline provides breast conserving patients with a new energy option of 7 MeV for boost of the shallow tumor bed. It would be an alternative to bolus and thus eliminate inconvenience and concern about the daily variation of bolus setup.

Effect of Time Interval between Breast-Conserving Surgery and Radiation Therapy on Outcomes of Node-Positive Breast Cancer Patients Treated with Adjuvant Doxorubicin/Cyclophosphamide Followed by Taxane.

PURPOSE: This study evaluated the effect of surgery-radiotherapy interval (SRI) on outcomes in patients treated with adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) and adjuvant four cycles of doxorubicin/cyclophosphamide (AC) followed by four cycles of taxane. MATERIALS AND METHODS: From 1999 to 2007, 397 eligible patients were diagnosed. The effect of SRI on outcomes was analyzed using a Cox proportional hazards model, and a maximal chi-square method was used to identify optimal cut-off value of SRI for each outcome. RESULTS: The median SRI was 6.7 months (range, 5.6 to 10.3 months). A SRI of 7 months was the significant cut-off value for distant metastasis-free survival (DMFS) and disease-free survival (DFS) using a maximal chi-square method. For overall survival, a significant cut-off value was not found. The patients with SRI > 7 months had worse 6-year DMFS and DFS than those with SRI ≤ 7 months on univariate analysis (DMFS, 81% vs. 91%, p=0.003; DFS, 78% vs. 89%, p=0.002). On multivariate analysis, SRI > 7 months did not affect DMFS and DFS. CONCLUSION: RT delayed for more than 7 months after BCS and adjuvant four cycles of AC followed by four cycles of taxane did not compromise clinical outcomes.

Concurrent Chemoradiotherapy Versus Chemotherapy Alone for Unresectable Locally Advanced Pancreatic Cancer: A Retrospective Cohort Study.

PURPOSE: The optimal treatment strategy for locally advanced pancreatic cancer (LAPC), particularly the role of concurrent chemoradiotherapy (CCRT), remains debatable. We compared the clinical outcomes of CCRT and palliative chemotherapy alone (CA) in patients with unresectable LAPC. MATERIALS AND METHODS: Patients with LAPC who were consecutively treated between 2003 and 2010 were included. Resectability was evaluated according to National Comprehensive Cancer Network ver. 1.2012. The clinical outcomes for each treatment group (CCRT vs. CA) were evaluated retrospectively. RESULTS: Sixty-three patients (58.9%) and 44 patients (41.1%) were treated with CCRT and CA, respectively. The CCRT cohort included patients who were treated with CCRT with or without chemotherapy backbone (CCRT alone, induction chemotherapy-CCRT, CCRT-maintenance chemotherapy, and induction-CCRT-maintenance chemotherapy). Median progression-free survival (PFS) and overall survival (OS) of all patients were 7.2 months and 13.1 months. PFS of the CCRT and CA groups was 9.0 months and 4.4 months, respectively (p=0.020). OS of the CCRT and CA groups was 15.4 months and 9.3 months, respectively (p=0.011). In multivariate analysis, the adjusted hazard ratio of CCRT was 0.536 (p=0.003) for OS and 0.667 (p=0.078) for PFS. Although the pattern of failure was similar in the CCRT and CA groups, the times to both local and distant failure were significantly longer in the CCRT group. CONCLUSION: In patients with unresectable LAPC, those who underwent CCRT during their entire treatment courses had longer OS than patients treated with chemotherapy alone.

Delayed Numerical Chromosome Aberrations in Human Fibroblasts by Low Dose of Radiation.

Radiation-induced genomic instability refers to a type of damage transmitted over many generations following irradiation. This delayed impact of radiation exposure may pose a high risk to human health and increases concern over the dose limit of radiation exposure for both the public and radiation workers. Therefore, the development of additional biomarkers is still needed for the detection of delayed responses following low doses of radiation exposure. In this study, we examined the effect of X-irradiation on delayed induction of numerical chromosomal aberrations in normal human fibroblasts irradiated with 20, 50 and 100 cGy of X-rays using the micronucleus-centromere assay. Frequencies of centromere negative- and positive-micronuclei, and aneuploidy of chromosome 1 and 4 were analyzed in the surviving cells at 28, 88 and 240 h after X-irradiation. X-irradiation increased the frequency of micronuclei (MN) in a dose-dependent manner in the cells at all measured time-points, but no significant differences in MN frequency among cell passages were observed. Aneuploid frequency of chromosomes 1 and 4 increased with radiation doses, and a significantly higher frequency of aneuploidy was observed in the surviving cells analyzed at 240 h compared to 28 h. These results indicate that low-dose of X-irradiation can induce delayed aneuploidy of chromosomes 1 and 4 in normal fibroblasts.

Outcome analysis in patients with uterine sarcoma.

PURPOSE: To analyze the prognostic factors for survivals and to evaluate the impact of postoperative whole pelvic radiotherapy (WPRT) on pelvic failure in patients with uterine sarcoma treated with radical surgery. MATERIALS AND METHODS: We retrospectively analyzed 75 patients with uterine sarcoma who underwent radical surgery with (n = 22) or without (n = 53) radiotherapy between 1990 and 2010. There were 23 and 52 patients with carcinosarcoma and non-carcinosarcoma (leiomyosarcoma, 22; endometrial stromal sarcoma, 25; others, 5), respectively. The median follow-up period was 64 months (range, 17 to 269 months). RESULTS: The 5-year overall survival (OS) and pelvic failure-free survival (PFFS) of total patients was 64.2% and 83.4%, respectively. Multivariate analysis revealed that mitotic count (p = 0.006) was a significant predictor of OS. However, factors were not found to be associated with PFFS. On analyzing each of the histologic subtypes separately, postoperative WPRT significantly reduced pelvic failure in patients with carcinosarcoma (10.0% vs. 53.7%; p = 0.046), but not in patients with non-carcinosarcoma (12.5% vs. 9.9%; p = 0.866). Among the patients with carcinosarcoma, 4 patients (17%) had recurrence within the pelvis and 3 patients (13%) had recurrence in other sites as an initial failure, whereas among the patients with non-carcinosarcoma, 3 patients (6%) experienced pelvic failure and 13 patients (25%) experienced distant failure. CONCLUSION: The most significant predictor of OS was mitotic count. Based on the improved PFFS after postoperative WPRT only in patients with carcinosarcoma and the difference in patterns of failure between histologic subtypes, optimal adjuvant treatment options should be offered to patients based on the risk of recurrence patterns.

A New Isolated Mediastinal Lymph Node or Small Pulmonary Nodule Arising during Breast Cancer Surveillance Following Curative Surgery: Clinical Factors That Differentiate Malignant from Benign Lesions.

PURPOSE: A newly isolated mediastinal lymph node (LN) or a small pulmonary nodule, which appears during breast cancer surveillance, may pose a diagnostic dilemma with regard to malignancy. We conducted this study to determine which clinical factors were useful for the differentiation of malignant lesions from benign lesions under these circumstances. MATERIALS AND METHODS: We enrolled breast cancer patients who were presented with a new isolated mediastinal LN or small pulmonary nodule that arose during surveillance, and whose lesions were pathologically confirmed. Tissue diagnosis was made by mediastinoscopy, video-assisted thoracic surgery or thoracotomy. RESULTS: A total of 43 patients were enrolled (mediastinal LN, 13 patients; pulmonary nodule, 30 patients). Eighteen patients (41.9%) were pathologically confirmed to have a benign lesion (benign group), and 25 patients (58.1%) were confirmed to have malignant lesion (malignant group). Between the two groups, the initial tumor size (p=0.096) and N stage (p=0.749) were similar. Hormone receptor negativity was more prevalent in the malignant group (59.1% vs. 40.9%, p=0.048). The mean lesion size was larger in the malignant group than in the benign group (20.8 mm vs. 14.4 mm, p=0.024). Metastatic lesions had a significantly higher value of maximal standardized uptake (mSUV) than that of benign lesions (6.4 vs. 3.4, p=0.021). CONCLUSION: Hormone receptor status, lesion size, and mSUV on positron emission tomography are helpful in the differentiation of malignant lesions from benign lesions in breast cancer patients who were presented with a new isolated mediastinal LN or small pulmonary nodule during surveillance.

Influence of boost radiotherapy in patients with ductal carcinoma in situ breast cancer: a multicenter, retrospective study in Korea (KROG 11-04).

To estimate the effect of boost radiotherapy on local recurrence-free survival (LRFS) in patients with ductal carcinoma in situ (DCIS) breast cancer. We included patients from nine institutions who met the following criteria: having Tis, age 18 years or older, having breast conserving surgery (BCS) and radiotherapy within 12 weeks after surgery. From 1995 through 2006, 728 patients were analyzed retrospectively by the Korean Radiation Oncology Group. All patients received whole-breast radiation therapy (WBRT) after BCS. 232 patients (31.9 %) also received boost radiation therapy (RT) (median 10 Gy). After median follow-up of 82 months, 5-year LRFS was 98.4 % and 10-year LRFS was 95.8 % for all patients. There was no statistically significant difference of LRFS between the boost and no-boost groups. Nineteen (2.6 %) patients had ipsilateral breast recurrences, including 12 of invasive recurrence and 7 DCIS. The presence of the HER2 receptor was associated with more invasive recurrences. Nine (1.2 %) patients developed contralateral breast cancer, including six invasive breast cancer and three DCIS. In the multivariate analysis, only the margin status was a significant prognostic factor for LRFS. Boost RT was not associated with further improvement of local control in DCIS after BCS and WBRT. HER2 receptor-positive patients may need further treatment with the anti-HER2 agents.

The effect of photon energy on intensity-modulated radiation therapy (IMRT) plans for prostate cancer.

PURPOSE: To evaluate the effect of common three photon energies (6-MV, 10-MV, and 15-MV) on intensity-modulated radiation therapy (IMRT) plans to treat prostate cancer patients. MATERIALS AND METHODS: Twenty patients with prostate cancer treated locally to 81.0 Gy were retrospectively studied. 6-MV, 10-MV, and 15-MV IMRT plans for each patient were generated using suitable planning objectives, dose constraints, and 8-field setting. The plans were analyzed in terms of dose-volume histogram for the target coverage, dose conformity, organs at risk (OAR) sparing, and normal tissue integral dose. RESULTS: Regardless of the energies chosen at the plans, the target coverage, conformity, and homogeneity of the plans were similar. However, there was a significant dose increase in rectal wall and femoral heads for 6-MV compared to those for 10-MV and 15-MV. The V(20 Gy) of rectal wall with 6-MV, 10-MV, and 15-MV were 95.6%, 88.4%, and 89.4% while the mean dose to femoral heads were 31.7, 25.9, and 26.3 Gy, respectively. Integral doses to the normal tissues in higher energy (10-MV and 15-MV) plans were reduced by about 7%. Overall, integral doses in mid and low dose regions in 6-MV plans were increased by up to 13%. CONCLUSION: In this study, 10-MV prostate IMRT plans showed better OAR sparing and less integral doses than the 6-MV. The biological and clinical significance of this finding remains to be determined afterward, considering neutron dose contribution.

Phase II clinical trial of induction chemotherapy with fixed dose rate gemcitabine and cisplatin followed by concurrent chemoradiotherapy with capecitabine for locally advanced pancreatic cancer.

PURPOSE: 5-FU-based concurrent chemoradiotherapy (CRT) has been the mainstay of treatment for locally advanced pancreatic cancer (LAPC) for the past decades, but the prognosis remains dismal. METHODS: Patients with pathologically confirmed LAPC of the pancreas, an ECOG PS of 0-2 and no prior chemo- or radiotherapy were eligible. The treatment consisted of induction (IND) chemotherapy with a fixed dose rate gemcitabine 1,000 mg/m(2) on days 1 and 8 and CDDP 60 mg/m(2) on day 1 every 3 weeks for 3 cycles. Subsequently, the patients without progression received CRT of 55.8 Gy/31 fractions with capecitabine 650 mg/m(2) twice daily. Gemcitabine was given for 3 cycles after CRT. The primary endpoint was time to progression. RESULTS: Thirty-seven patients with LAPC were enrolled. Median age was 55 years, there were 20 males and 17 females, and ECOG PS was 0 in 6 and 1 in 31. Three patients (9.7 %) achieved partial responses after IND chemotherapy. Twenty-five patients received CRT with a mean radiation dose of 54.0 Gy, with one additional patient achieving a partial response. The median time to progression was 7.2 months (95 % CI, 4.4-10), and the median overall survival was 16.8 months (95 % CI, 12.9-20.7). The grade 3/4 toxicities included neutropenia (29 %/6.5 %), thrombocytopenia (3.2 %/0 %) and anemia (9.7 %/0 %) during the IND phase and grade 3 neutropenia and diarrhea occurring in one and two patients during CRT phase. CONCLUSIONS: IND chemotherapy with gemcitabine and cisplatin followed by CRT with capecitabine and maintenance gemcitabine was well tolerated and exhibited promising efficacy for the treatment of LAPC.

Changes in biologic markers of oxidative stress and plasma endotoxin levels in gynecologic cancer patients treated with pelvic radiotherapy: a pilot study.

OBJECTIVE: We conducted a pilot study to evaluate the effects of pelvic radiotherapy on biologic markers of oxidative stress and plasma endotoxin levels, and to assess the relationship between the changes of such factors and radiotherapy-related complications. METHODS: Twelve gynecologic cancer patients who were treated via pelvic radiotherapy with or without concurrent chemotherapy were enrolled in this study. Biologic markers of oxidative stress, such as glutathione (GSH) and oxidized glutathione (GSSG), as well as endotoxin levels, were measured weekly during treatment. Subjective symptoms were assessed using the Korean version of the EORTC QLQ-C30 at the baseline and on the 5th week of radiotherapy. RESULTS: No changes were noted in the level of GSH in whole blood, but the GSH/GSSG ratio was reduced dramatically after the initiation of radiotherapy. The mean plasma endotoxin for all patients tended to increase and persisted during radiotherapy, and the number of patients who evidenced clinically significant endotoxin levels (defined as >0.005 EU/mL) also increased. Nausea/vomiting and diarrhea were significantly changed (p=0.019 and p<0.001, respectively). A significant relationship was noted to exist between the changes in the endotoxin level and nausea/vomiting (p=0.001). However, such symptoms did not correlate with the changes of oxidative stress markers. CONCLUSION: Pelvic radiotherapy oxidized the GSH redox system and increased plasma endotoxin. Further investigations containing interventional and longitudinal studies will be required to assess the effects of the changes in oxidative stress markers and endotoxin on radiotherapy-related adverse events.

Definitive radiotherapy for treatment of primary vaginal cancer: effectiveness and prognostic factors.

OBJECTIVE: This study was performed to evaluate treatment outcomes and define prognostic factors for primary vaginal cancer treated with definitive radiotherapy. MATERIALS AND METHODS: We retrospectively analyzed 38 patients with primary vaginal cancer who received radiotherapy with curative intent between January 1981 and August 2008. Of these 38 patients, 6 were excluded from this analysis because of other uncontrolled malignancy (n = 1), uncommon histology (n = 4), or insufficient medical records (n = 1). Twenty-three patients (72%) presented with early-stage disease (International Federation of Gynecology and Obstetrics stages 0, I, or II). Eleven patients (34%) were treated with external beam radiotherapy (EBRT) alone and 21 patients (66%) with EBRT plus brachytherapy (BT). Low-dose rate cesium-137 was used with intracavitary technique for most of the patients who received BT. Five patients received chemotherapy. The median total dose in patients who received EBRT and EBRT+BT was 50.4 Gy (range, 39.6-70.4 Gy) and 78.9 Gy (range, 72.0-87.0 Gy), respectively. RESULTS: The median duration of follow-up was 38 months. Five-year overall survival, cause-specific survival, disease-free survival, local control, and regional control rates for the analyzed patients were 75%, 88%, 58%, 62% and 90%, respectively. Thirteen patients had treatment failure as follows: local (n = 7), distant (n = 1), local plus regional (n = 1), local plus distant (n = 2), and local plus regional plus distant (n = 2). Primary tumor size was a significant prognostic factor for disease-free survival (P = 0.039). CONCLUSIONS: Definitive radiotherapy is an effective treatment modality for primary vaginal cancer. Local failure was the major failure pattern, and achievement of local control is important for disease control and survival.

Clinical outcome of central nervous system metastases from breast cancer: differences in survival depending on systemic treatment.

Central nerve system (CNS) metastases are a feared complication of breast cancer and are associated with poor prognosis. The purpose of this study is to investigate the clinical characteristics of CNS metastases and to clarify the prognostic factors after CNS metastases in breast cancer at a single institution over a long time period. We retrospectively reviewed the medical records of breast cancer patients diagnosed at Seoul National University Hospital from 1981 to 2009 and identified the patients who experienced CNS metastases. We collected the data, including demographics, clinico-pathologic characteristics, dates of diagnosis of original breast cancer and subsequent metastases, and date of death, and correlated the findings with the clinical outcome. A total of 400 patients were identified, of whom 17 (4.3%) were diagnosed with CNS metastases and primary breast cancer concurrently and 383 (95.7%) experienced CNS metastases subsequent to the diagnosis of primary breast cancer. Further, 318 patients (79.5%) had only brain parenchymal metastases, 30 (7.5%) had only leptomeningeal metastases, and 52 (13%) had both. After the diagnosis of CNS metastasis, 170 patients (42.5%) received systemic chemotherapy (CTx) and 143 (35.8%) received CTx after whole brain radiation therapy (WBRT). The patients with good performance status (PS), initial CNS metastasis as recurrence, absence of extracranial metastases, non-visceral extracranial metastases, longer interval from the date of primary breast cancer to the date of CNS metastasis, and CTx after WBRT and gamma-knife surgery (GKS), had better outcomes in univariate analyses. In multivariate analysis, good PS, systemic CTx after WBRT, GKS, and longer interval to CNS metastasis, were independent prognostic factors for overall survival after CNS metastases. Our results suggest that appropriate palliative systemic therapy after WBRT or GKS, and adequate palliative treatment via combined modalities are helpful for breast cancer patients, even after the detection of CNS metastases.

Phase II trial of preoperative paclitaxel, gemcitabine, and trastuzumab combination therapy in HER2 positive stage II/III breast cancer: the Korean Cancer Study Group BR 07-01.

An addition of trastuzumab preoperatively to chemotherapy for human epidermal growth factor receptor 2 (HER2) positive breast cancer improved relapse-free survival (RFS). This study was designed to evaluate the efficacy and safety of preoperative paclitaxel, gemcitabine, and trastuzumab (PGH) combination for HER2-positive breast caner. Pathologically, proven node positive stage II/III breast cancer patients with adequate organ function and no history of anti-cancer therapy were eligible. Patients received weekly trastuzumab with paclitaxel 80 mg/m(2) and gemcitabine 1,200 mg/m(2) on days 1 and 8, every 3 weeks for 6 cycles. Postoperatively, patients completed trastuzumab for 1 year and hormone therapy for 5 years if indicated. All patients received postoperative radiation therapy. Of 53 enrolled patients with a median tumor of 5.3 (range, 2.0 to >12) cm; 43.4%, T3/T4; 75.4%, N2/N3; and 45.3%, positive hormone receptors. The pathologic complete response (pCR) rate was 58.5% in both tumor and lymph nodes. Grade 3/4 adverse events were neutropenia (32%), febrile neutropenia (0.6%), and transient elevation of AST/ALT (1.6%) during a total of 318 cycles. All patients maintained normal cardiac function. With a median follow-up of 40 months, 3-year RFS rate was 84% with 91.7% distant metastasis-free survival rates. Remarkable pCR rate was obtained with non-anthracycline-based PGH therapy for HER2-positive stage II/III breast cancer. Adverse events were mild with few incidences of febrile neutropenia.

Dosimetry of a new P-32 ophthalmic applicator.

PURPOSE: The potential of P-32 ophthalmic applicator irradiation after pterygium excision has been demonstrated as an alternative to Sr∕Y-90 irradiation. This study aimed to provide the clinical dosimetry for this new applicator. METHODS: The prototype of a cylindrical P-32 applicator was fabricated according to the Monte Carlo (MC)-based design study. At a nominal activity of 6 mCi (0.22 GBq), the absorbed dose rate at the front surface (i.e., reference dose rate) was measured by using an extrapolation ionization chamber (EC). The radiochromic film (RCF) was also used to measure the reference dose, axial depth dose distributions and transaxial dose profiles at various depths in water. RESULTS: The reference dose rate was 3.89 ± 0.14 cGy∕s for EC and 3.84 ± 0.25 cGy∕s for RCF. The depth dose rate was reduced approximately by an order of magnitude for every 2 mm depth in water. Measured depth doses in depths of 0.5-2.5 mm agreed with Monte Carlo data within ±3%. Due to nonuniform absorption of P-32 into an absorbent disk, the dose profiles were not symmetric and decreased more rapidly toward the periphery than those predicted by the MC. The authors confirmed no leakage of P-32 activities and negligible exposure rate around the hand grip of the applicator. CONCLUSIONS: The P-32 applicator can deliver therapeutic doses to the surface of the conjunctiva, while sparing the lens better than Sr∕Y-90 applicators. The doses at any points from the P-32 applicator could be calculated by using the measured dosimetry data. They also confirmed no leakage of the source, reliable integrity of the applicator, and negligible exposure level around the hand grip of the applicator. However, due to a possibility of nonuniform distributions of P-32 in an absorbent disk, measuring dose profiles as well as the reference dose rate for every new applicator would be recommended.

The dosimetric effect of mixed-energy IMRT plans for prostate cancer.

We investigated the effect of mixing high- and low-energy photon beams on the quality of intensity-modulated radiation therapy (IMRT) plans for patients with prostate cancer. Three different plans for each of twenty patients were generated using either 6 MV or 15 MV alone, and both 6 and 15 MV beams. All the planning parameters, goals, and constraints were set to be identical except beam energy. The dose distributions were similar in terms of target coverage, conformity, and homogeneity regardless of beam energy. The V(70Gy) of rectal wall in 6 MV, 15 MV and mixed-energy plans was 16.7%, 17.9%, and 16.3%, respectively, while V(40Gy) was 55.6%, 53.2%, and 50%. The mean dose to femoral heads in 6 MV, 15 MV, and mixed-energy plans were 31.7 Gy, 26.3 Gy, and 26.2 Gy, respectively. The integral dose of 6 MV plans was 7% larger than those of 15 MV or mixed-energy plans. These results indicated that mixed-energy IMRT plans could take advantage of the dosimetric characteristics of low- and high-energy beams. Even though the reduction of dose to the organs at risk may not be clinically relevant, mixing energy in an IMRT plan for deep-seated tumors can improve the overall plan quality.

Diagnostic performance of contrast enhanced CT and 18F-FDG PET/CT in suspicious recurrence of biliary tract cancer after curative resection.

BACKGROUND: Because of the late clinical presentation of biliary tract cancer (BTC), only 10% of patients are eligible for curative surgery. Even among those patients who have undergone curative surgery, most patients develop recurrent cancer. This study is to determine the clinical role of 18F-FDG PET/CT during post-operative surveillance of suspected recurrent BTC based on symptoms, laboratory findings and contrast-enhanced CT (ceCT) findings. METHODS: We consecutively enrolled 50 patients with BTC who underwent curative surgery. An 18F-FDG PET/CT was obtained for assessment of recurrence based on clinical suspicion during post-operative surveillance. The final confirmation of recurrence was determined pathologically or clinically. When a pathologic confirmation was impossible or inconclusive, a clinical confirmation was used by radiologic correlation with subsequent follow-up ceCT at a minimum of 3-month intervals. Diagnostic efficacy was evaluated by comparing the results of ceCT and 18F-FDG PET/CT with the final diagnosis. RESULTS: Among the 50 patients, 34(68%) were confirmed to have a recurrence. PET/CT showed higher sensitivity (88% vs. 76%, p=0.16) and accuracy (82% vs. 66%, p=0.11) for recurrence compared to ceCT, even though the difference was not significant. The positive (86% vs. 74%, p=0.72) and negative predictive values for recurrence (73% vs. 47%, p=0.55) were not significantly different between PET/CT and ceCT. However, an additional PET/CT on ceCT significantly improved the sensitivity than did a ceCT alone (94% [32/34] for PET/CT on ceCT vs. 76% [26/34] for ceCT alone, p=0.03) without increasing the specificity, positive predictive value, and negative predictive value. CONCLUSIONS: 18F-FDG PET/CT alone is not more sensitive or specific than ceCT in the detection of recurrent BTC after curative surgery. These results do not reach statistical significance, probably due to the low number of patients. However, an additional 18F-FDG PET/CT on ceCT significantly improves the sensitivity of detecting recurrences.

Statistical analysis of IMRT dosimetry quality assurance measurements for local delivery guideline.

PURPOSE: To establish our institutional guideline for IMRT delivery, we statistically evaluated the results of dosimetry quality assurance (DQA) measurements and derived local confidence limits using the concept confidence limit of |mean|+1.96σ. MATERIALS AND METHODS: From June 2006 to March 2009, 206 patients with head and neck cancer, prostate cancer, liver cancer, or brain tumor were treated using LINAC-based IMRT technique. In order to determine site specific DQA tolerances at a later stage, a hybrid plan with the same fluence maps as in the treatment plan was generated on CT images of a cylindrical phantom of acryl. Points of measurement using a 0.125 cm3 ion-chamber were typically located in the region of high and uniform doses. The planar dose distributions perpendicular to the central axis were measured by using a diode array in solid water with all fields delivered, and assessed using gamma criteria of 3%/3 mm. The mean values and standard deviations were used to develop the local confidence and tolerance limits. The dose differences and gamma pass rates for the different treatment sites were also evaluated in terms of total monitor uints (MU), MU/cGy, and the number of PTV's pieces. RESULTS: The mean values and standard deviations of ion-chamber dosimetry differences between calculated and measured doses were -1.6 ± 1.2% for H&N cancer, -0.4 ± 1.2% for prostate and abdominal cancer, and -0.6 ± 1.5% for brain tumor. Most of measured doses (92.2%) agreed with the calculated doses within a tolerance limit of ±3% recommended in the literature. However, we found some systematic under-dosage for all treatment sites. The percentage of points passing the gamma criteria, averaged over all treatment sites was 97.3 ± 3.7%. The gamma pass rate and the agreement of ion-chamber dosimetry generally decreased with increasing the number of PTV's pieces, the degree of modulation (MU/cGy), and the total MU beyond 700. Our local confidence limits were comparable to those of AAPM TG 119 and ESTRO guidelines that were provided as a practical baseline for center-to-center commissioning comparison. Thus, our institutional confidence and action limits for IMRT delivery were set into the same levels of those guidelines. DISCUSSION AND CONCLUSIONS: The systematic under-dosage were corrected by tuning up the MLC-related factors (dosimetric gap and transmission) in treatment planning system (TPS) and further by incorporating the tongue-and groove effect into TPS. Institutions that have performed IMRT DQA measurements over a certain period of time need to analyze their accrued DQA data. We confirmed the overall integrity of our IMRT system and established the IMRT delivery guideline during this procedure. Dosimetric corrections for the treatment plans outside of the action level can be suggested only with such rigorous DQA and statistical analysis.

Outcomes of positron emission tomography-staged clinical N3 breast cancer treated with neoadjuvant chemotherapy, surgery, and radiotherapy.

PURPOSE: To evaluate the treatment outcome and efficacy of regional lymph node irradiation after neoadjuvant chemotherapy (NCT) and surgery in positron emission tomography (PET)-positive clinical N3 (cN3) breast cancer patients. METHODS AND MATERIALS: A total of 55 patients with ipsilateral infraclavicular (ICL), internal mammary (IMN), or supraclavicular (SCL) lymph node involvement in the absence of distant metastases, as revealed by an initial PET scan, were retrospectively analyzed. The clinical nodal stage at diagnosis (2002 AJCC) was cN3a in 14 patients (26%), cN3b in 12 patients (22%), and cN3c in 29 patients (53%). All patients were treated with NCT, followed by mastectomy or breast-conserving surgery and subsequent radiotherapy (RT) with curative intent. RESULTS: At the median follow-up of 38 months (range, 9-80 months), 20 patients (36%) had developed treatment failures, including distant metastases either alone or combined with locoregional recurrences that included one ipsilateral breast recurrence (IBR), six regional failures (RF), and one case of combined IBR and RF. Only 3 patients (5.5%) exhibited treatment failure at the initial PET-positive clinical N3 lymph node. The 5-year locoregional relapse-free survival, disease-free survival (DFS), and overall survival rates were 80%, 60%, and 79%, respectively. RT delivered to PET-positive IMN regions in cN3b patients and at higher doses (≥55 Gy) to SCL regions in cN3c patients was not associated with improved 5-year IMN/SCL relapse-free survival or DFS. CONCLUSION: NCT followed by surgery and RT, including the regional lymph nodes, resulted in excellent locoregional control for patients with PET-positive cN3 breast cancer. The primary treatment failure in this group was due to distant metastasis rather than RF. Neither higher-dose RT directed at PET-positive SCL nodes nor coverage of PET-positive IMN nodes was associated with additional gains in locoregional control or DFS.

The value of preoperative staging chest computed tomography to detect asymptomatic lung and liver metastasis in patients with primary breast carcinoma.

Little is known about the benefits of preoperative staging chest computed tomography (CT) in patients with asymptomatic breast cancer. We therefore investigated the clinical value of preoperative chest CT in detecting lung and liver metastases by retrospectively reviewing the records of 1,703 patients who underwent preoperative chest CT in a single institution between January 2006 and June 2009. Abnormal CT findings, including suspected metastases and indeterminate nodules in the lung or liver, were found in 266 patients (15.6%). Among these, 26 patients (1.5% of all patients and 9.8% of patients with abnormal CT findings) had true metastases, including 17 in the lungs, 3 in the liver, and 6 in both. True metastases were detected in 1 (0.2%), 0 (0%), and 24 (6.0%) patients with stage I, II, and III disease, respectively. The sensitivity, specificity, and positive predictive value of chest CT were 100, 89.1, and 11.3%, respectively, for lung metastasis and 100, 97.6, and 18.4%, respectively, for liver metastasis. All true metastatic lung lesions were all small-sized nodules, ranging from 0.2 to 1.5 cm in largest diameter, and could not be detected on chest X-rays. In conclusion, our results demonstrate the lack of usefulness of routine preoperative chest CT in detecting asymptomatic liver and lung metastasis in patients with early breast cancer. Chest CT, however, upstaged 6.0% of stage III patients to stage IV.