Association Between Thyroid Radiation Dose and Hypothyroidism in Breast Cancer Patients Undergoing Volumetric Modulated Arc Therapy for Regional Nodal Irradiation.

BACKGROUND/AIM: To investigate the association between the thyroid dysfunction and thyroid radiation dose in regional nodal irradiation (RNI) using volumetric modulated arc therapy (VMAT) for breast cancer. PATIENTS AND METHODS: We reviewed medical data of 67 patients with breast cancer who underwent curative surgery followed by adjuvant radiotherapy, including RNI using VMAT, between 2018 and 2021. All patients had normal thyroid functional test results, including thyroid stimulating hormone (TSH), T3, and free-T4. We defined subclinical hypothyroidism as increased TSH with or without decreased levels of free-T4 and T3 after the completion of VMAT. We calculated dose-volume histogram parameters (DVHPs), including the mean dose and relative thyroid volume receiving at least 10, 20, 30, and 40 Gy. RESULTS: The median follow-up time was 23.2 months. The 3-year locoregional failure-free survival, progression-free survival, and overall survival rates were 96.3%, 94.7%, and 96.2%, respectively. The mean thyroid dose was 21.4 Gy (range=11.5-29.4 Gy). Subclinical hypothyroidism was noted in 14 patients (20.9%) and the median time to the event was 4.1 months. Among the DVHPs, the relative volume receiving ≥20 Gy (V20Gy) was associated with subclinical hypothyroidism. The 2-year rates of subclinical hypothyroidism were 24.8% and 59.1% in patients with V20Gy ≤46.3% and >46.3%, respectively. CONCLUSION: A significant proportion of patients with breast cancer developed subclinical hypothyroidism after undergoing VMAT for RNI. Our findings highlight the importance of considering the thyroid as an organ at risk for VMAT planning, and suggest that V20Gy could be a useful dose-volume constraint.

Effects of Radiation Dose on Liver After Free-breathing Volumetric Modulated Arc Therapy for Breast Cancer.

BACKGROUND/AIM: To evaluate the early effect of radiation dose on liver function in breast cancer patients undergoing free-breathing volumetric modulated arc therapy (FB-VMAT). PATIENTS AND METHODS: Medical records of 125 patients with breast cancer who underwent curative surgery followed by postoperative radiotherapy using FB-VMAT during 2018-2021 were reviewed. Results of the liver function test (LFT), performed within 1-week before and 6-months after radiotherapy, were collected and compared. The LFTs analyzed albumin, total and direct bilirubin, aspartate transaminase, alanine transferase, and alkaline phosphatase levels. The mean dose and relative liver volume receiving at least 10 Gy, 20 Gy, or 30 Gy were calculated. RESULTS: Median follow-up time was 21.4 months. One patient experienced locoregional and distant failures. The mean liver irradiation dose was 325.9 centigray (cGy) for all patients. The liver irradiation dose was higher in patients with right breast cancer than in those with left breast cancer (mean, 434.1 cGy vs. 260.6 cGy, p<0.001). Direct bilirubin and aspartate transaminase levels showed significant differences after FB-VMAT. LFT results outside normal limits were noted in 31 patients at follow-up, but nobody met the criteria of radiation-induced liver disease. Underlying liver disease, breast laterality, systemic treatment, or dose-volume histogram parameters were not associated with abnormal LFT results. CONCLUSION: FB-VMAT can deliver radiation doses safely without adversely affecting the liver. The mean dose ≤4 Gy could be a useful dose criterium of the liver for FB-VMAT plans.

Antitumor effects of IL-12 and GM-CSF co-expressed in an engineered oncolytic HSV-1.

Oncolytic viruses selectively replicate and destroy cancer cells while sparing normal cells, prompting their recognition as promising antitumor agents. Herpes simplex virus (HSV) is suitable as an anticancer agent, given its considerable therapeutic gene capacity and excellent safety profile in clinical trials. Interleukin (IL)-12 induces a Th1-type immune response that mediates interferon (IFN)-γ release from natural killer (NK), CD4+ and CD8+ T cells. Granulocyte-macrophage colony-stimulating factor (GM-CSF) induces the generation of antigen-presenting cells and promotes dendritic cell differentiation. We established a novel oncolytic HSV-1 (∆6/GM/IL12) co-expressing IL-12 and GM-CSF and tested its effects against a B16-F10 murine melanoma model. ∆6/GM/IL12 administration diminished tumor growth and prolonged survival compared to treatment with ∆6/GM or ∆6/IL12 expressing each individual cytokine. Flow cytometry and histological analysis showed increased activation of CD4+ and CD8+ T cells in ∆6/GM/IL12-treated mice. Enzyme-linked immunosorbent spot assay showed an increase in the phenotypically characterized IFN-γ-producing cell population in ∆6/GM/IL12-treated mice. Moreover, ∆6/GM/IL12 induced a B16-F10-specific cytotoxic immune response that enhanced IFN-γ production by CD3+CD8+ T cells. Therefore, IL-12 and GM-CSF from an engineered oncolytic HSV have a synergistic effect, boosting the immune response to increase their antitumor effects.

Enhancement of megavoltage electronic portal images for markerless tumor tracking.

PURPOSE: The poor quality of megavoltage (MV) images from electronic portal imaging device (EPID) hinders visual verification of tumor targeting accuracy particularly during markerless tumor tracking. The aim of this study was to investigate the effect of a few representative image processing treatments on visual verification and detection capability of tumors under auto tracking. METHODS: Images of QC-3 quality phantom, a single patient's setup image, and cine images of two-lung cancer patients were acquired. Three image processing methods were individually employed to the same original images. For each deblurring, contrast enhancement, and denoising, a total variation deconvolution, contrast-limited adaptive histogram equalization (CLAHE), and median filter were adopted, respectively. To study the effect of image enhancement on tumor auto-detection, a tumor tracking algorithm was adopted in which the tumor position was determined as the minimum point of the mean of the sum of squared pixel differences (MSSD) between two images. The detectability and accuracy were compared. RESULTS: Deblurring of a quality phantom image yielded sharper edges, while the contrast-enhanced image was more readable with improved structural differentiation. Meanwhile, the denoising operation resulted in noise reduction, however, at the cost of sharpness. Based on comparison of pixel value profiles, contrast enhancement outperformed others in image perception. During the tracking experiment, only contrast enhancement resulted in tumor detection in all images using our tracking algorithm. Deblurring failed to determine the target position in two frames out of a total of 75 images. For original and denoised set, target location was not determined for the same five images. Meanwhile, deblurred image showed increased detection accuracy compared with the original set. The denoised image resulted in decreased accuracy. In the case of contrast-improved set, the tracking accuracy was nearly maintained as that of the original image. CONCLUSIONS: Considering the effect of each processing on tumor tracking and the visual perception in a limited time, contrast enhancement would be the first consideration to visually verify the tracking accuracy of tumors on MV EPID without sacrificing tumor detectability and detection accuracy.

Bond strength of individual carbon nanotubes grown directly on carbon fibers.

The performance of carbon nanotube (CNT)-based devices strongly depends on the adhesion of CNTs to the substrate on which they were directly grown. We report on the bond strength of CNTs grown on a carbon fiber (T700SC Toray), measured via in situ pulling of individual CNTs inside a transmission electron microscope. The bond strength of an individual CNT, obtained from the measured pulling force and CNT cross-section, was very high (∼200 MPa), 8-10 times higher than that of an adhesion model assuming only van der Waals interactions (25 MPa), presumably due to carbon-carbon interactions between the CNT (its bottom atoms) and the carbon substrate.

Tumor response assessment by the single-lesion measurement per organ in small cell lung cancer.

BACKGROUND: The criterion of two target lesions per organ in the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 is an arbitrary one, being supported by no objective evidence. The optimal number of target lesions per organ still needs to be investigated. We compared tumor responses using the RECIST 1.1 (measuring two target lesions per organ) and modified RECIST 1.1 (measuring the single largest lesion in each organ) in patients with small cell lung cancer (SCLC). METHODS: We reviewed medical records of patients with SCLC who received first-line treatment between January 2004 and December 2014 and compared tumor responses according to the two criteria using computed tomography. RESULTS: There were a total of 34 patients who had at least two target lesions in any organ according to the RECIST 1.1 during the study period. The differences in the percentage changes of the sum of tumor measurements between RECIST 1.1 and modified RECIST 1.1 were all within 13%. Seven patients showed complete response and fourteen showed partial response according to the RECIST 1.1. The overall response rate was 61.8%. When assessing with the modified RECIST 1.1 instead of the RECIST 1.1, tumor responses showed perfect concordance between the two criteria (k=1.0). CONCLUSIONS: The modified RECIST 1.1 showed perfect agreement with the original RECIST 1.1 in the assessment of tumor response of SCLC. Our result suggests that it may be enough to measure the single largest target lesion per organ for evaluating tumor response.

Electron dose distributions caused by the contact-type metallic eye shield: Studies using Monte Carlo and pencil beam algorithms.

A metallic contact eye shield has sometimes been used for eyelid treatment, but dose distribution has never been reported for a patient case. This study aimed to show the shield-incorporated CT-based dose distribution using the Pinnacle system and Monte Carlo (MC) calculation for 3 patient cases. For the artifact-free CT scan, an acrylic shield machined as the same size as that of the tungsten shield was used. For the MC calculation, BEAMnrc and DOSXYZnrc were used for the 6-MeV electron beam of the Varian 21EX, in which information for the tungsten, stainless steel, and aluminum material for the eye shield was used. The same plan was generated on the Pinnacle system and both were compared. The use of the acrylic shield produced clear CT images, enabling delineation of the regions of interest, and yielded CT-based dose calculation for the metallic shield. Both the MC and the Pinnacle systems showed a similar dose distribution downstream of the eye shield, reflecting the blocking effect of the metallic eye shield. The major difference between the MC and the Pinnacle results was the target eyelid dose upstream of the shield such that the Pinnacle system underestimated the dose by 19 to 28% and 11 to 18% for the maximum and the mean doses, respectively. The pattern of dose difference between the MC and the Pinnacle systems was similar to that in the previous phantom study. In conclusion, the metallic eye shield was successfully incorporated into the CT-based planning, and the accurate dose calculation requires MC simulation.

Analysis of predictive factors for lung injury after forward-planned intensity-modulated radiotherapy in whole breast irradiation.

PURPOSE: This study was performed to assess frequency, timings of occurrence, and predictors of radiologic lung damage (RLD) after forward-planned intensity-modulated radiotherapy (FIMRT) for whole breast irradiation. METHODS: We retrospectively reviewed medical records of 157 breast cancer patients and each of their serial chest computed tomography (CT) taken 4, 10, 16, and 22 months after completion of breast radiotherapy (RT). FIMRT was administered to whole breast only (n=152), or whole breast and supraclavicular regions (n=5). Dosimetric parameters, such as mean lung dose and lung volume receiving more than 10 to 50 Gy (V10-V50), and clinical parameters were analyzed in relation to radiologic lung damage. RESULTS: In total, 104 patients (66.2%) developed RLD after whole breast FIMRT. Among the cases of RLD, 84.7% were detected at 4 months, and 15.3% at 10 months after completion of RT. More patients of 47 or younger were found to have RLD at 10 months after RT than patients older than the age (11.7% vs. 2.9%, p=0.01). In univariate and multivariate analyses, age >47 and V40 >7.2% were significant predictors for higher risk of RLD. CONCLUSION: RLD were not infrequently detected in follow-up CT after whole breast FIMRT. More detected cases of RLD among younger patients are believed to have developed at later points after RT than those of older patients. Age and V40 were significant predictors for RLD after whole breast intensity-modulated radiotherapy.

Clinical features and treatment outcomes of skin cancer arising from burn scar: a single-institution experience.

AIMS AND BACKGROUND: This study was conducted to investigate the clinicopathological features and long-term outcomes of patients with skin cancer arising from burn scar (SCBS). PATIENTS AND METHODS: We retrospectively reviewed the medical records of patients diagnosed with SCBS between January 2000 and May 2012. A total of 44 patients were enrolled in this study. RESULTS: The median latent period between burn injury and development of SCBS was 32 years (range, 8-78 years). The most frequent sites of SCBS were the lower limbs (68.2%) followed by the upper limbs (15.9%) and trunk (11.4%). Most patients (95.4%) had squamous cell carcinoma. Of 34 patients with localized disease at the time of diagnosis, 33 patients are alive with no evidence of recurrence. Of 10 patients with regional lymph node metastasis (referred to as locally advanced disease), 4 died of disease progression and 5 are alive with metastatic disease in the lymph nodes, bone or lung. Patients with localized disease survived longer than patients with locally advanced disease ( P = 0.000). In patients with locally advanced disease, the median overall survival time was 16 months (95% CI, 2.88-29.4 months). CONCLUSIONS: While localized SCBS is a potentially curable disease, locally advanced SCBS has a poor prognosis in spite of aggressive treatment. These results suggest that early recognition and aggressive treatment are essential to improve the outcomes of SCBS.

3D braid scaffolds for regeneration of articular cartilage.

Regenerating articular cartilage in vivo from cultured chondrocytes requires that the cells be cultured and implanted within a biocompatible, biodegradable scaffold. Such scaffolds must be mechanically stable; otherwise chondrocytes would not be supported and patients would experience severe pain. Here we report a new 3D braid scaffold that matches the anisotropic (gradient) mechanical properties of natural articular cartilage and is permissive to cell cultivation. To design an optimal structure, the scaffold unit cell was mathematically modeled and imported into finite element analysis. Based on this analysis, a 3D braid structure with gradient axial yarn distribution was designed and manufactured using a custom-built braiding machine. The mechanical properties of the 3D braid scaffold were evaluated and compared with simulated results, demonstrating that a multi-scale approach consisting of unit cell modeling and continuum analysis facilitates design of scaffolds that meet the requirements for mechanical compatibility with tissues.

The application of PET-CT to post-mastectomy regional radiation therapy using a deformable image registration.

BACKGROUND: To evaluate the utility of the preoperative PET-CT using deformable image registration (DIR) in the treatment of patients with locally advanced breast cancer and to find appropriate radiotherapy technique for further adequate treatment of axillary nodal area. METHODS: Sixty-five breast cancer patients who had level II, III axillary or supraclavicular lymph node metastasis on ¹8F-FDG PET-CT and received postoperative radiotherapy after modified radical mastectomy were enrolled. One radiation oncologist contoured normal organs (axillary vessels, clavicular head, coracoids process and humeral head) and involved lymph nodes on PET-CT and simulation CT slices. After contouring, deformable image registration of PET-CT on simulation CT was carried out. To evaluate the performance of the DIR, Dice similarity coefficient (DSC) and Center of mass (COM) were used. We created two plans, one was the historically designed three field plan and the other was the modified plan based on the location of axillary lymph node, and we compared the doses that irradiated the axillary lymph nodes. RESULTS: The DSCs for axillary artery, axillary vein, clavicular head, coracoids process and humeral head were 0.43 ± 0.15, 0.39 ± 0.20, 0.85 ± 0.10, 0.72 ± 0.20 and 0.77 ± 0.20, respectively. The distances between the COMs of axillary artery, axillary vein, clavicular head, coracoids process and humeral head in simulation CT and from PET-CT were 13.0 ±7.1, 20.2 ± 11.2, 4.4 ± 6.3, 3.7 ± 6.7, and 9.5 ± 25.0 mm, respectively. In the historically designed plan, only 57.7% of level II lymph nodes received more than 95% of prescribed dose and the coverage was improved to 70.0% with the modified plan (p < 0.01). For level III lymph nodes, the volumes received more than 95% of prescribed dose were similar in both plans (96.8 % vs 97.9%, p = 0.35). CONCLUSION: Deformable image registration of PET-CT on simulation CT was helpful in the identification of the location of the preoperatively involved axillary lymph node. Historically designed three-field plan was not adequate to treat the axillary level II lymph node area. Novel treatment technique based on the location of axillary lymph node from PET-CT using DIR can result in more adequate coverage of nodal area.

Application of a dummy eye shield for electron treatment planning.

Metallic eye shields have been widely used for near-eye treatments to protect critical regions, but have never been incorporated into treatment plans because of the unwanted appearance of the metal artifacts on CT images. The purpose of this work was to test the use of an acrylic dummy eye shield as a substitute for a metallic eye shield during CT scans. An acrylic dummy shield of the same size as the tungsten eye shield was machined and CT scanned. The BEAMnrc and the DOSXYZnrc were used for the Monte Carlo (MC) simulation, with the appropriate material information and density for the aluminum cover, steel knob and tungsten body of the eye shield. The Pinnacle adopting the Hogstrom electron pencil-beam algorithm was used for the one-port 6-MeV beam plan after delineation and density override of the metallic parts. The results were confirmed with the metal oxide semiconductor field effect transistor (MOSFET) detectors and the Gafchromic EBT2 film measurements. For both the maximum eyelid dose over the shield and the maximum dose under the shield, the MC results agreed with the EBT2 measurements within 1.7%. For the Pinnacle plan, the maximum dose under the shield agreed with the MC within 0.3%; however, the eyelid dose differed by -19.3%. The adoption of the acrylic dummy eye shield was successful for the treatment plan. However, the Pinnacle pencil-beam algorithm was not sufficient to predict the eyelid dose on the tungsten shield, and more accurate algorithms like MC should be considered for a treatment plan.

Factors governing the growth mode of carbon nanotubes on carbon-based substrates.

The formation of carbon nanotubes (CNTs) through precipitated carbons emerging from supersaturated metal catalysts is an established mechanism for their growth during the CVD process. Here, the CNT growth mode is determined by the interaction between the substrate and the catalyst nanoparticle, e.g., the tip-growth mode for the weak adhesion between them and the base-growth mode for the strong adhesion case. With microscopic evidence, this study reports another factor that governs the growth mode of CNTs on carbon-based substrates. Catalyst nanoparticles after only sputtering and annealing processes before the chemical vapor deposition (CVD) process are fully or partially wrapped with some graphitic layers, which are formed by carbons escaping from the carbon substrate. The formation of the wrapping graphitic layers is initiated by catalyst atoms diffusing into the carbon substrate during the catalyst sputtering process. The diffused catalyst atoms later coalesce into the nanoparticles, during which carbon atoms escape from the carbon substrate, forming the graphitic layers which wrap around the catalyst nanoparticles for energy minimization. Then, the carbon atoms generated from the catalytic reactions during the CVD process interact with the carbons in the graphitic layers wrapped around the catalyst nanoparticles, bringing about clear tip-growth of CNTs on carbon-based substrates and a stable interface (carbon-carbon bonding) between CNTs and carbon-based substrates.

Degradation and healing mechanisms of carbon fibers during the catalytic growth of carbon nanotubes on their surfaces.

This study reports on the main cause of the reduced tensile strength of carbon fibers (CFs) by investigating the microstructural changes in the CFs that are undergoing mainly two processes: catalyst nanoparticle formation and chemical vapor deposition (CVD). Interestingly, the two processes oppositely influenced the tensile strength of the CFs: the former negatively and the latter positively. The catalysts coating and nanoparticle formation degraded the CF surface by inducing amorphous carbons and severing graphitic layers, while those defects were healed by both the injected carbons and interfaced CNTs during the CVD process. The revealed degradation and healing mechanisms can serve as a fundamental engineering basis for exploring optimized processes in the manufacturing of hierarchical reinforcements without sacrificing the tensile strength of the substrate CFs.

Evaluation of delivered monitor unit accuracy of gated step-and-shoot IMRT using a two-dimensional detector array.

PURPOSE: To overcome the problem of organ motion in intensity-modulated radiation therapy (IMRT), gated IMRT is often used for the treatment of lung cancer. In this study, the authors investigated the accuracy of the delivered monitor units (MUs) from each segment during gated IMRT using a two-dimensional detector array for user-specific verification purpose. METHODS: The authors planned a 6 MV photon, seven-port step-and-shoot lung IMRT delivery. The respiration signals for gated IMRT delivery were obtained from the one-dimensional moving phantom using the real-time position management (RPM) system (Varian Medical Systems, Palo Alto, CA). The beams were delivered using a Clinac iX (Varian Medical Systems, Palo Alto, CA) with the Millennium 120 MLC. The MatriXX (IBA Dosimetry GmbH, Germany) was validated through consistency and reproducibility tests as well as comparison with measurements from a Farmer-type ion chamber. The authors delivered beams with varying dose rates and duty cycles and analyzed the MatriXX data to evaluate MU delivery accuracy. RESULTS: There was quite good agreement between the planned segment MUs and the MUs computed from the MatriXX within +/- 2% error. The beam-on times computed from the MatriXX data were almost identical for all cases, and they matched well with the RPM beam-on and beam-off signals. A slight difference was observed between them, but it was less than 40 ms. The gated IMRT delivery demonstrated an MU delivery accuracy that was equivalent to ungated IMRT, and the delivered MUs with a gating signal agreed with the planned MUs within +/- 0.5 MU regardless of dose rate and duty cycle. CONCLUSIONS: The authors can conclude that gated IMRT is able to deliver an accurate dose to a patient during a procedure. The authors believe that the methodology and results can be transferred to other vendors' devices, particularly those that do not provide MLC log data for a verification purpose.

Systemic chemotherapy after cranial irradiation in patients with brain metastases from non-small cell lung cancer: a retrospective study.

BACKGROUND: Brain metastases (BMs) are found in about 10% of patients with newly diagnosed non-small cell lung cancer (NSCLC). This retrospective study was conducted to assess the clinical outcomes and prognostic factors of patients who received chemotherapy after cranial irradiation for NSCLC with synchronous BMs. MATERIALS AND METHODS: From January 2000 through July 2007, we reviewed the medical records of patients who received systemic chemotherapy following cranial irradiation for BMs from newly diagnosed NSCLC. RESULTS: A total of 40 patients were included in this review. As the first-line chemotherapy, a total of 114 cycles were administered, for a median number of 2 cycles per patient (range, 0.5-8 cycles). Thirty-four patients (85%) received platinum-based combination regimen and the remaining 6 received chemotherapy with a single agent. Sixteen (40%) patients, 11 of whom had ECOG of 2, only received 1 cycle or less of chemotherapy due to early death, rapid progression, clinical impairment, or toxicity. For 28 patients who were evaluable for response, the extracranial overall response rate was 43%. The median overall survival for all patients was 7 months (range, 0.9-25.3 months) and an estimated 1-year survival rate was 23%. Multivariate analysis revealed that ECOG status (P=0.018) and number of BM (P=0.038) were independent prognostic factors. CONCLUSION: Our results suggest that chemotherapy can be used to increase survival of patients treated with cranial irradiation for newly diagnosed NSCLC with synchronous BM. However, systemic chemotherapy should be carefully considered according to the patient's prognostic condition. Especially, patients with good performance status and limited number of BM may be good candidates for systemic chemotherapy after cranial irradiation.

Dosimetric characteristics of linear accelerator photon beams with small monitor unit settings.

Several studies on the effect of tumor cell killing by dose rate variation have implied that the use of a shorter treatment time is more favorable for intensity modulated radiation therapy (IMRT). Aiming at step-and-shoot IMRT with higher dose rates, the stabilities of beam output and profiles with small monitor unit (MU) settings were investigated for various dose rates. With the use of a Varian 21EX (Varian Medical Systems Inc., Palo Alto, CA), static and step-and-shoot IMRT beam output along with profiles were measured by use of an ion chamber and a two-dimensional diode array detector as a function of monitor units and dose rates. For a static case, as the MU approached 1, the beam output increased up to 2% for 300 MU/min and 4.5% for 600 MU/min, showing a larger overdose as the dose rate increased. Deterioration of the beam symmetry and flatness were also observed as the MU decreased to 1 monitor unit. For the step-and-shoot IMRT case, a large dosimetric error of more than 10% was also detected with the use of a small MU segment. However, no definite correlation with the dose rate was observed due to the combined beam start-up effects by the grid pulse and finite communication time between the machine console and multileaf collimator (MLC) controller. For step-and-shoot IMRT with higher dose rates, beam output and beam profile stability with small MU needs to be checked, and adequate MU limitation where segments are not allowed need to be reflected in the step-and-shoot IMRT planning.

Analyses on prognostic factors following tri-modality therapy for stage IIIa non-small cell lung cancer.

This study is to evaluate and report the prognostic factors of N2 positive stage IIIA non-small cell lung cancer (NSCLC) treated with concurrent radiochemotherapy (CRCT) and surgery. CRCT and surgery were planned in 66 patients with stage IIIA NSCLC, and 46 evaluable patients were analyzed. Thoracic radiation therapy (TRT) dose was 45 Gy over 5 weeks, chemotherapy consisted of two cycles of intravenous cisplatin (100mg/m(2), on days 1 and 29 of TRT) and oral etoposide (50mg/m(2)/day, on days 1-14 and 29-42 of TRT), and surgery was performed in 4 weeks following CRCT completion. With the median follow up duration of 23 (range 5-74) months, the overall survival, disease-free survival, and local control rates at 5 years in all patients were 27%, 24% and 90%, respectively. The overall survival and disease-free survival rates at 5 years in the patients who achieved ypN0 stage and ypN1/2 stages were 47% and 0% (p=0.008), and 42% and 7% (p=0.01), respectively. The corresponding figures in those with initial "bulky" N2 disease and "mediastinoscopic" N2 disease were 31% and 19% (p=0.98), and 23% and 26% (p=0.68), respectively. Following CRCT and surgery, achieving ypN0 stage turned out to be a significantly favorable indicator, while the initial mediastinal lymph node extent did not, with respect to overall survival and disease-free survival.

Treatment results and prognostic factors of early breast cancer treated with a breast conserving operation and radiotherapy.

BACKGROUND: The purpose of this study was to analyze the prognostic factors affecting local control and survival rates for patients with early breast cancer who received breast conserving treatment (BCT) and to find out the optimal treatment according to their risk factors. METHODS: From October 1994 to December 2001, 605 patients with 611 stage I and II breast cancers received BCT, and the results were analyzed retrospectively. BCT consists of breast conserving surgery and whole breast irradiation. All the patients underwent lumpectomy or quadrantectomy. Axillary lymph node dissection or sentinel lymph node biopsy was performed in 608 cases (99.5%). The radiation dose to the whole breast was 50.4 Gy over 5 weeks with a 1.8 Gy daily fraction and with boost doses of 9-14.4 Gy administered to the tumor bed. Adjuvant chemotherapy was performed in most of the patients with axillary lymph node metastasis or tumors larger than 1 cm. The median follow-up period was 47 months. RESULTS: Local relapse, regional relapse and distant metastasis occurred in 15 (2.5%), 16 (2.6%) and 43 patients (7.1%), respectively. The 5-year overall survival, local-relapse-free survival, distant-metastasis-free survival and disease-free survival rates were 95.3%, 97.2%, 91.3% and 88.5%, respectively. On multivariate analysis, age (P = 0.02), number of involved axillary lymph nodes (P = 0.01) and nuclear grade (P = 0.01) affected the local-relapse-free survival. The factors associated with disease-free survival were the T stage (P = 0.05), number of involved axillary lymph nodes (P = 0.01) and nuclear grade (P = 0.001). Overall survival was associated with the T stage (P = 0.02), number of involved axillary lymph nodes (P = 0.01) and c-erb B2 overexpression (P = 0.05). Patients with more than two factors among (i) age 1 cm, (ii) positive lymph node metastasis and (iii) high nuclear grade showed an inferior 5-year disease-free survival rate compared with others (P = 0.0005). CONCLUSIONS: The most important prognostic factor affecting local control, disease-free survival and overall survival was axillary lymph node metastasis. The nuclear grade influenced local control and disease relapse. Patients with multiple unfavorable risk factors such as positive axillary lymph nodes, high nuclear grade, young age and large tumor showed poorer local control and disease-free survival than patients without any risk factors, and so more aggressive treatment is required for these patients.

Patterns of Failure and Prognostic Factors in Anal Cancer Treated with Radiotherapy.

PURPOSE: To analyze the patterns of failure and prognostic factors affecting the local control and survivals in anal cancer treated with definitive radiotherapy, and to find the most effective treatment modality. MATERIALS AND METHODS: Thirty consecutive patients, with primary cancers of the anal canal, were treated using radiotherapy, both with and without 5-FU based concurrent chemotherapy. According to the AJCC tumor stage, six patients hadwere stage I, 11 had stage II, 2 had stage IIIA, and 11 had stage IIIB tumors. The median radiation dose was 45 Gy (30-72 Gy), and with 23 patients receivinged concurrent chemotherapy (5-FU and mitomycin C in 12 patients, 5-FU and cisplatin in 7, and other drugs in 4). The Mmedian follow up period was 43 months, (ranginge, from 8- to 99 months). RESULTS: Among the 1630 patients who16 were treated without surgical resection beforeprior to the radiotherapy, and a complete remission was observed in 12 patients (75%), a partial remission in 3 (19%), and a local progression in the other one patient. The Llocal failures, including persistent disease, were observed in 10 (33%), and the patients with higher T-stages (T3-4) had higher rates of local failure rates (T1-2, 21% vs. T3-4, 72%, p=0.03). Distant metastases were found in 4 patients (13%). The five year survival and disease free survival rates were 64% and 53%, respectively. The factors which affectinged the 5 year local relapse free survival were T-stage (74.9% in T1-2 vs. 28.6% in T3-4, p=0.01), and the existence of a gross tumor beforeprior to radiotherapy (84.6%, no residual vs. 45.1% with residual, p=0.03). CONCLUSION: A Llocal recurrence was the major failure pattern in anal cancers, and the factors affecting a local failure were the T-stage and tumor volume beforeprior to radiotherapy. A Rradiation dose around 45 Gy was sufficient to control tumors of the earlier T stage tumors, but a higher dose should be considered for with more advanced lesions.