Jiayi Chen

Planning the breast boost: How accurately do surgical clips represent the CT seroma?

BACKGROUND AND PURPOSE To measure the distance between surgical clips and edge of CT-defined seroma in a coronal plane in women who have undergone wide local excision of breast cancer and to evaluate dosimetric coverage of CT-defined boost volumes by conventional clip-based electron fields. MATERIALS AND METHODS Planning CT images of 30 lumpectomy cavities from 30 patients were reviewed. All seroma cavities had at least 4 clips and Cavity Visualization Score ≥3. Distances between clips and seroma edge (D(c-s)) were measured at the radial margins for each patient. Clips-based electron fields were generated by including all the clips with 2 cm margin in the coronal plane and three-dimensional conformal radiotherapy plans (3D-CRT) were devised based on CT tumor beds (CT-TBs). The parameters of dose-volume histogram between the two boost treatment plans were analyzed. RESULTS The mean seroma edge extended beyond the clips by 0.3-0.5 cm. In all 120 D(c-s)s, 76.7% were ≤0.5 cm, 8.3% were >1 cm and 15% were between 0.5 and 1 cm. Twenty patients (20/30) had D(c-smax) (The maximal D(c-s) of each patient) >0.5 cm and 7 patients had D(c-smax) >1 cm. With the electron fields, only 46.7% (14/30) had D(90) (The minimal dose received by 90% of the planning target volume (PTV)) >90% and geographical miss (any portion of the PTV receiving <50% of the prescribed dose) was found in 36.7% (11/30). D(c-smax) >0.5 cm was associated with D(90) <90% (P<0.001) and >1 cm was associated with geographic miss (P=0.001). CONCLUSIONS Surgical clips are not always consistent with the edge of seroma. Electron boost field based on clips leads to insufficient dose coverage to the CT-TB. 3D-CRT planning should be considered to ameliorate the dose coverage to the tumor bed.

Post mastectomy linac IMRT irradiation of chest wall and regional nodes: dosimetry data and acute toxicities

BackgroundConventional post-mastectomy radiation therapy is delivered with tangential fields for chest wall and separate fields for regional nodes. Although chest wall and regional nodes delineation has been discussed with RTOG contouring atlas, CT-based planning to treat chest wall and regional nodes as a whole target has not been widely accepted. We herein discuss the dosimetric characteristics of a linac IMRT technique for treating chest wall and regional nodes as a whole PTV after modified radical mastectomy, and observe acute toxicities following irradiation.MethodsPatients indicated for PMRT were eligible. Chest wall and supra/infraclavicular region +/−internal mammary nodes were contoured as a whole PTV on planning CT. A simplified linac IMRT plan was designed using either integrated full beams or two segments of half beams split at caudal edge of clavicle head. DVHs were used to evaluate plans. The acute toxicities were followed up regularly.ResultsTotally, 85 patients were enrolled. Of these, 45 had left-sided lesions, and 35 received IMN irradiation. Planning designs yielded 55 integrated and 30 segmented plans, with median number of beams of 8 (6–12). The integrated and segmented plans had similar conformity (1.41±0.14 vs. 1.47±0.15, p=0.053) and homogeneity indexes (0.13±0.01 vs. 0.14±0.02, p=0.069). The percent volume of PTV receiving >110% prescription dose was <5%. As compared to segmented plans, integrated plans typically increased V5 of ipsilateral lung (p=0.005), and heart (p=0.001) in patients with left-sided lesions. Similarly, integrated plans had higher spinal cord Dmax (p=0.009), ipsilateral humeral head (p<0.001), and contralateral lung Dmean (p=0.019). During follow-up, 36 (42%) were identified to have ≥ grade 2 radiation dermatitis (RD). Of these, 35 developed moist desquamation. The median time to onset of moist desquamation was 6 (4–7) weeks from start of RT. The sites of moist desquamation were most frequently occurred in anterior axillary fold (32/35), and secondly chest wall (12/35). The difference in occurrence of ≥ grade 2 RD between integrated and segmented plans was statistically insignificant (X2=0.35, p=0.55). Only 2 were found to have grade 2 radiation pneumonitis.ConclusionsThe linac IMRT technique applied in PMRT with chest wall and regional nodes as a whole PTV was dosimetrically feasible, and the treatment was proved to be well-tolerated by most patients.

Radiotherapy Can Improve the Disease-Free Survival Rate in Triple-Negative Breast Cancer Patients with T1–T2 Disease and One to Three Positive Lymph Nodes After Mastectomy

PURPOSE Several studies have demonstrated poor locoregional control in patients with triple-negative breast cancer (TNBC), compared with other molecular subtypes of breast cancer. We sought to evaluate whether or not postmastectomy radiotherapy (PMRT) improves locoregional recurrence-free survival (LRFS) and disease-free survival (DFS) outcomes in TNBC patients. METHODS AND MATERIALS Between January 2000 and July 2007, 553 TNBC patients treated with modified radical mastectomy from a single institution were analyzed retrospectively. Patients were categorized into three groups: low risk (stage T1-T2N0), intermediate risk (stage T1-T2N1), and high risk (stage T3-T4 and/or N2-N3). Cox proportional hazards models were used to evaluate the association between PMRT and LRFS and DFS times after adjusting for other clinicopathologic covariates. RESULTS With a median follow-up of 65 months (range, 1-140 months), 51 patients (9.2%) developed locoregional recurrence and 135 patients (24.4%) experienced disease recurrence. On multivariate analysis, PMRT was associated with significantly longer LRFS and DFS times in the entire cohort. In the intermediate-risk group, PMRT was associated with a longer DFS time but not with the LRFS interval. In the high-risk group, PMRT was associated with significantly longer LRFS and DFS times. CONCLUSION PMRT is associated with longer LRFS and DFS times in high-risk TNBC patients and a longer DFS time in intermediate-risk TNBC patients. Prospective randomized studies are needed to investigate the best locoregional treatment approaches for patients with this molecular subtype of breast cancer.

Analysis in early stage triple-negative breast cancer treated with mastectomy without adjuvant radiotherapy: patterns of failure and prognostic factors.

The objective of this study was to evaluate and identify patterns of failure and prognostic factors for locoregional recurrence (LRR) that could justify postmastectomy radiotherapy after modified radical mastectomy in patients with early stage triple‐negative breast cancer.

Early cardiac toxicity following adjuvant radiotherapy of left-sided breast cancer with or without concurrent trastuzumab

Purpose To evaluate the influence of concurrent trastuzumab on the cardiotoxicity in patients receiving left-sided adjuvant radiotherapy. Materials and Methods Medical records of stage I-III left-sided breast cancer patients, including 64 receiving concurrent trastuzumab with radiotherapy and 73 receiving radiotherapy alone were retrospectively reviewed. All of the patients had normal LVEF after adjuvant chemotherapy. Information of doses volume to cardiac structures was collected. Cardiac events were assessed according to CTC 2.0. Results Median follow-up of LVEF and clinical assessment of cardiac function from the initiation of radiotherapy was 6.7 months (range 3–60.9) and 26 months (range 6.4–60.9), respectively. Grade 1 LVEF dysfunction occurred in 5 (7.8%) and 3 (4.1%) patients of the concurrent-trastuzumab and radiotherapy alone cohort, respectively. Trastuzumab was the only significant factor influencing absolute LVEF decrease in univariate analysis. In multivariate analysis of concurrent-trastuzumab cohort, IMC radiotherapy and start trastuzumab during radiotherapy were independent risk factors. For concurrent cohort, mean heart dose, as well as D10-D30, D50-D55, V5-V20 of the heart and D30-D45, D65-D75, V6-V15 of the LV were significantly higher in patients developing LVEF dysfunction. Conclusions Concurrent trastuzumab and left-sided radiotherapy is well tolerated in terms of cardiotoxicity in patients with normal baseline cardiac function after adjuvant chemotherapy. However, increases in mean dose and low–dose volume of cardiac structures are associated with a higher risk of acute LVEF dysfunction.

Using corrected Cone-Beam CT image for accelerated partial breast irradiation treatment dose verification: the preliminary experience

BackgroundAccurate target localization is mandatory in the accelerated partial breast irradiation (APBI) delivery. Dosimetric verification for positional error will further guarantee the accuracy of treatment delivery. The purpose of this study is to evaluate the clinical feasibility of a cone beam computer tomographic (CBCT) image correction method in APBI.MethodsA CBCT image correction method was developed. First, rigid image registration was proceeded for CTs and CBCTs; second, these images were separated into four parts; then, ratio images for each of the four parts of planning CTs/CBCTs were calculated and filtered to reduce the high spatial frequency; finally, the enhanced CBCT images were generated combing the four parts. An anthropomorphic thorax rando phantom was used to evaluate the feasibility and accuracy of the CBCT correction method. The CBCT images of consecutive 10 patients receiving APBI were corrected using the above method and dosimetric variations were evaluated. Each set of CBCT is composed of three images: one acquired after skin-marker setup, one after online setup correction and one after treatment delivery.ResultsThe phantom study showed the improved accuracy of dose calculation with corrected CBCT. The Dose Volume Histogram (DVH) difference between the planning CT and corrected CBCT is less than the difference between the planning CT and original CBCT. The maximum dose difference between the corrected CBCT and planning CT is 0.8% in PTV_EVAL V100, which is 3.8% between original CBCT and planning. In the patient study, 67.4% of fractions benefit from CBCT setup corrections in PTV_EVAL D95, while in 47.4% of the fractions, reduced dose coverage was found on the post-treatment CBCT. Overall, the CBCT based initial setup correction guaranteed target dose coverage in 9 patients.ConclusionsA generic CBCT image correction algorithm was created and proved to be easily implemented in clinic. Compared to the original CBCT, the corrected CBCT has more accuracy in dose calculation. The CBCT guided APBI based on initial skin setup is not sufficient to guarantee the accurate dose delivery throughout each fraction. The long treatment delivery time may compromise the target coverage benefits in some patients.

PV-0425: EEF2K promotes progression and radioresistance of esophageal squamous cell carcinoma

OBJECTIVES To investigate the biological function of eEF2K in esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS Tissue microarrays containing 100 pairs of ESCC tumor and adjacent normal tissues were completed. Overexpression and knockdown of eEF2K were constructed in ECA-109 and TE-13 ESCC cells. DNA damage, cell viability, migration and invasion, radioresistance, apoptosis and autophagy were determined by immunofluorescence, CCK-8, transwell assay, colony formation assay, flow cytometry and western blot, respectively. Tumor growth and radioresistance were also evaluated using xenograft models created in nude mice. RESULTS eEF2K expression was higher in ESCC tissues compared with matched non-tumor tissues (P<0.05). Proliferation was increased in eEF2K overexpressing cells compared with controls (P<0.05), while silencing eEF2K reduced cell proliferation (P<0.05). Furthermore, lower levels of eEF2K expression correlated with slower migration and invasion rates (P<0.05), while higher levels of eEF2K expression with faster migration and invasion rates (P<0.05). eEF2K overexpression resulted in radioresistance and radiation-induced autophagy, and reduced radiation-induced apoptosis compared with controls, but silencing eEF2K promoted radiosensitivity and apoptosis, and reduced autophagy. In addition, eEF2K overexpression promoted the tumor growth in vivo (P<0.01). Combined treatment of NH125 (a pharmacological inhibitor of eEF2K) and radiation was more effective at delaying xenograft tumor growth than NH125 and radiation alone (P<0.05). CONCLUSION eEF2K induced progression and radioresistance in ESCC, which may be a novel therapeutic target for ESCC to increase radiosensitivity.

Multibeam inverse intensity-modulated radiotherapy (IMRT) for whole breast irradiation: A single center experience in China

Purpose To present the clinical experience in our cancer center with multibeam inverse intensity-modulated radiotherapy (IMRT) for early stage breast cancer (BC) patients with whole breast irradiation (WBI). Methods We retrospectively analyzed 622 patients with Stage 0 to III BC treated from 2008 to 2011 with wide local excision and WBI, using an inverse IMRT technique. All of the patients were prescribed a total dose of 50 Gy to the whole breast in 2-Gy fractions, followed by a tumor bed boost of 10 Gy in 5 fractions using an electron beam. Results Of all of the patients, 132 (21.2%) received whole breast plus regional lymph node (RLN) irradiation. 438 of 622 patients had records of acute skin toxicity based on common terminology criteria (CTC) for adverse events. Two hundred eighty (64%) patients had Grade 0/1 toxicity, 153 (35%) had Grade 2 and only 4 patients experienced grade 3 toxicity. Seventy patients (16%) had moist desquamation. Univariate analysis revealed that breast planning target volume was the only predictive factor for Grade ≥2 acute dermatitis (P = 0.002). After 4 years, 170 patients reported cosmetic results by self-assessment, of whom 151 (89%) patients reported good/excellent cosmetic results, and 17 (11%) patients reported fair assessments. For invasive cancer, the four-year rate of freedom from locoregional recurrence survival was 98.3%. Regarding carcinoma in situ, no patients experienced recurrence. Conclusion BC patients who underwent conservative surgery followed by inverse IMRT plan exhibited acceptable acute toxicities and clinical outcomes. Longer follow-up is needed.

A comparison of efficacy and toxicity between never-smokers and smokers with lung adenocarcinoma after concurrent gefitinib and thoracic radiotherapy.

e13586 Background: There is limited data on the outcomes of Asian smoker or never-smoker lung adenocarcinoma patients treated with concurrent gefitinib and radiotherapy. We herein report our observations from a phase I trial (NCT 00497250). Methods: Patients with stage IIIB or selected stage IV, failure of platinum-based chemotherapy regimen NSCLC were eligible. Four cohorts of eight patients each were planned to be treated with escalating doses from 54 to 60 Gy of conformal or intensity-modulated radiotherapy administered in combination with gefitinib 250 mg daily during and 60 days after the completion of RT. To December 2009, a total of 28 patients were eligible for this analysis. Among them, there were 8 stage IIIb and 20 stage IV, 17 were never-smokers, and 11 smokers. Results: After a median follow-up time of 9 months (95% CI: 1.6-21.2) for the entire group, the median survival was 17 months (95% CI: 12-24) and 14 months (95% CI: 6-22), and 1-yr survival was 76% and 61%, respectively for never-smoke...