ming Shi

4D‐CT scans reveal reduced magnitude of respiratory liver motion achieved by different abdominal compression plate positions in patients with intrahepatic tumors undergoing helical tomotherapy

PURPOSE While abdominal compression (AC) can be used to reduce respiratory liver motion in patients receiving helical tomotherapy for hepatocellular carcinoma, the nature and extent of this effect is not well described. The purpose of this study was to evaluate the changes in magnitude of three-dimensional liver motion with abdominal compression using four-dimensional (4D) computed tomography (CT) images of several plate positions. METHODS From January 2012 to October 2015, 72 patients with intrahepatic carcinoma and divided into four groups underwent 4D-CT scans to assess respiratory liver motion. Of the 72 patients, 19 underwent abdominal compression of the cephalic area between the subxiphoid and umbilicus (group A), 16 underwent abdominal compression of the caudal region between the subxiphoid area and the umbilicus (group B), 11 patients underwent abdominal compression of the caudal umbilicus (group C), and 26 patients remained free breathing (group D). 4D-CT images were sorted into ten-image series, according to the respiratory phase from the end inspiration to the end expiration, and then transferred to treatment planning software. All liver contours were drawn by a single physician and confirmed by a second physician. Liver relative coordinates were automatically generated to calculate the liver respiratory motion in different axial directions to compile the 10 ten contours into a single composite image. Differences in respiratory liver motion were assessed with a one-way analysis of variance test of significance. RESULTS The average respiratory liver motion in the Y axial direction was 4.53 ± 1.16, 7.56 ± 1.30, 9.95 ± 2.32, and 9.53 ± 2.62 mm in groups A, B, C, and D, respectively, with a significant change among the four groups (p < 0.001). Abdominal compression was most effective in group A (compression plate on the subxiphoid area), with liver displacement being 2.53 ± 0.93, 4.53 ± 1.16, and 2.14 ± 0.92 mm on the X-, Y-, and Z-axes, respectively. There was no significant difference in respiratory liver motion between group C (displacement: 3.23 ± 1.47, 9.95 ± 2.32, and 2.92 ± 1.10 mm on the X-, Y-, and Z-axes, respectively) and group D (displacement: 3.35 ± 1.55, 9.53 ± 2.62, and 3.35 ± 1.73 mm on the X-, Y-, and Z-axes, respectively). Abdominal compression was least effective in group C (compression on caudal umbilicus), with liver motion in this group similar to that of free-breathing patients (group D). CONCLUSIONS 4D-CT scans revealed significant liver motion control via abdominal compression of the subxiphoid area; however, this control of liver motion was not observed with compression of the caudal umbilicus. The authors, therefore, recommend compression of the subxiphoid area in patients undergoing external radiotherapy for intrahepatic carcinoma.

Comparison of Effects Between Central and Peripheral Stage I Lung Cancer Using Image-Guided Stereotactic Body Radiotherapy via Helical Tomotherapy.

Lung cancer is a common malignant tumor with high morbidity and mortality. Here we compared the effects and outcome between central and peripheral stage I lung cancer using image-guided stereotactic body radiotherapy. From June 2011 to July 2013, a total of 33 patients with stage I lung cancer were enrolled. A total of 50 Gy in 10 fractions or 60 Gy in 10 fractions was delivered in the central arm (n = 18), while 50 Gy in 5 fractions in the peripheral arm (n = 15). Statistical analyses were performed using logistic regression analysis and Kaplan-Meier method. The mean follow-up time was 38.1 months. Three-month, 1-, 2-, and 3-year overall response rates were 66.7%, 83.3%, 61.1%, and 72.2% and 66.7%, 80%, 80%, and 80% in the central and peripheral arms, respectively. Three-year local control rates (94.4% vs 93.3%, P = .854), regional control rates (94.4% vs 86.7%, P = .412), and distant control rates (64.2% vs 61.7%, P = .509) had no differences between the central and the peripheral arms. Grade 2 radiation pneumonitis was observed in 6 of 18 patients in the central arm and in 1 of 15 patients in the peripheral arm (P = .92). Grade 2 radiation esophagitis was 5.7% in the central arm, while none occurred in the peripheral arm (P = .008). Five (15.1%) of all patients felt slight fatigue during radiotherapy. Other major complications were not observed. In conclusion, helical image-guided stereotactic body radiotherapy for central stage I lung cancer is safe and effective compared to peripheral stage I lung cancer.

Feasibility and efficacy of helical intensity-modulated radiotherapy for stage III non-small cell lung cancer in comparison with conventionally fractionated 3D-CRT

BACKGROUND The standard treatment for stage III non-small-cell lung cancer (NSCLC) is still 60 Gy in conventional fractions combined with concurrent chemotherapy; however, the resulting local controls are disappointing. The aim of this study was to compare and assess the feasibility and efficacy of hypofractionated chemoradiotherapy using helical tomotherapy (HT) with conventional fractionation as opposed to using three-dimensional conformal radiotherapy (3D-CRT) for stage III NSCLC. METHODS Sixty-nine patients with stage III (AJCC 7th edition) NSCLC who underwent definitive radiation treatment at our institution between July 2011 and November 2013 were reviewed and analyzed retrospectively. A dose of 60 Gy in 20 fractions was delivered in the HT group (n=34), whereas 60 Gy in 30 fractions in the 3D-CRT group (n=35). Primary endpoints were toxicity, overall response rate, overall survival (OS) and progression-free survival (PFS). RESULTS The median follow-up period was 26.4 months. V20 (P=0.005), V30 (P=0.001), V40 (P=0.004), mean lung dose (P=0.000) and max dose of spinal cord (P=0.005) were significantly lower in the HT group than in the 3D-CRT group. There was no significant difference in the incidences of acute radiation pneumonitis (RP) ≥ grade 2 between the two groups, whereas the incidences of acute radiation esophagitis ≥ grade 2 were significantly lower in the HT group than in the 3D-CRT group (P=0.027). Two-year overall response rate was significantly higher in the HT group than in the 3D-CRT group (P=0.015). One- and 2-year OS rates were significantly higher in the HT group (95.0% and 68.7%, respectively) than in the 3D-CRT group (85.5% and 47.6%, respectively; P=0.0236). One- and 2-year PFS rates were significantly higher in the HT group (57.8% and 26.3%, respectively) than in the 3D-CRT group (32.7% and 11.4%, respectively; P=0.0351). Univariate analysis indicated that performance status (PS), T stage and radiotherapy technique were significant prognostic factors for both OS and PFS. Multivariate analysis indicated that PS and radiotherapy technique were independent prognostic factors of OS and PS was independent prognostic factor of PFS. CONCLUSIONS Hypofractionated chemoradiotherapy via HT can shorten the radiotherapy time without increasing treatment-related toxicity. The preliminary findings are that OS and PFS can be improved by hypofractionated chemoradiotherapy via HT for patients with stage III NSCLC.

Evaluation of the 7 th edition of the UICC-AJCC tumor, node, metastasis classification for esophageal cancer in a Chinese cohort

BACKGROUND To assess and evaluate the prognostic value of the 7(th) edition of the Union for International Cancer Control-American Joint Committee on Cancer (UICC-AJCC) tumor, node, metastasis (TNM) staging system for Chinese patients with esophageal cancer in comparison with the 6(th) edition. METHODS A retrospective review was performed on 766 consecutive esophageal cancer patients treated with esophagectomy between 2008 and 2012. Patients were staged according to the 6(th) and 7(th) editions for esophageal cancer respectively. Survival was calculated by the Kaplan-Meier method, and multivariate analysis was performed using Cox regression model. RESULTS Overall 3-year survival rate was 59.5%. There were significant differences in 3-year survival rates among T stages both according to the 6(th) edition and the 7(th) edition (P<0.001). According to the 7(th) edition, the 3-year survival rates of N0 (75.4%), N1 (65.2%), N2 (39.7%) and N3 (27.3%) patients were significant differences (P<0.001). Kaplan-Meier curve revealed a good discriminatory ability from stage I to IV, except for stage IB, IIA and IIB in the 7(th) edition staging system. Based on the 7(th) edition, the degree of differentiation, tumor length and tumor location were not independent prognostic factors on multivariate analysis. The multivariate analyses suggested that pT-, pN-, pTNM-category were all the independent prognostic factors based on the 6(th) and 7(th) edition staging system. CONCLUSIONS The 7(th) edition of AJCC TNM staging system of esophageal cancer should discriminate pT2-3N0M0 (stage IB, IIA and IIB) better when considering the esophageal squamous cell cancer patients. Therefore, to improve and optimize the AJCC TNM classification for Chinese patients with esophageal cancer, more considerations about the value of tumor grade and tumor location in pT2-3N0M0 esophageal squamous cell cancer should be taken in the next new TNM staging system.

Prognostic value of systemic inflammation score in patients with hepatocellular carcinoma after hepatectomy

Inflammation plays an important role in cancer progression. In this study, we aimed to investigate the prognostic value of the systemic inflammatory biomarkers in hepatocellular carcinoma (HCC) patients undergoing curative resection. Data from 271 HCC patients who underwent curative resection in Zhongshan Hospital between 2008 and 2011 were included. Kaplan-Meier survival analysis showed that gamma-glutamyltransferase (GGT) and lymphocyte-to-monocyte ratio (LMR) were significantly associated with overall survival(OS) and time to recurrence(TTR). We created a systemic inflammation score (SIS) basing on preoperative serum GGT and LMR. Low SIS was also significantly associated with increased OS and TTR. Univariate and multivariate analyses revealed the LMR, GGT and SIS were independent predictors for OS and TTR. The predictive ability of the SIS, as assessed by area under the receiver operating characteristic curve, was 0.682 (95% CI, 0.618-0.746) for OS, which was higher than GGT and LMR. In conclusion, low preoperative LMR and high preoperative GGT were associated with a poor prognosis in HCC patients after hepatectomy. Our results confirmed that the SIS qualifies as a novel prognostic predictor of HCC patients after hepatectomy.Inflammation plays an important role in cancer progression. In this study, we aimed to investigate the prognostic value of the systemic inflammatory biomarkers in hepatocellular carcinoma (HCC) patients undergoing curative resection. Data from 271 HCC patients who underwent curative resection in Zhongshan Hospital between 2008 and 2011 were included. Kaplan-Meier survival analysis showed that gamma-glutamyltransferase (GGT) and lymphocyte-to-monocyte ratio (LMR) were significantly associated with overall survival(OS) and time to recurrence(TTR). We created a systemic inflammation score (SIS) basing on preoperative serum GGT and LMR. Low SIS was also significantly associated with increased OS and TTR. Univariate and multivariate analyses revealed the LMR, GGT and SIS were independent predictors for OS and TTR. The predictive ability of the SIS, as assessed by area under the receiver operating characteristic curve, was 0.682 (95% CI, 0.618-0.746) for OS, which was higher than GGT and LMR. In conclusion, low preoperative LMR and high preoperative GGT were associated with a poor prognosis in HCC patients after hepatectomy. Our results confirmed that the SIS qualifies as a novel prognostic predictor of HCC patients after hepatectomy.

Nomograms for predicting disease progression in patients of Stage I non-small cell lung cancer treated with stereotactic body radiotherapy

Objective Non-local progression is a major concern in non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT). Herein we aimed to create a pre-treatment prognostic nomogram for patients with Stage I NSCLC receiving SBRT. Methods We retrospectively studied 182 eligible patients. Patients were randomly divided into a model (70%) group and a validation (30%) group. In the model group, thirteen parameters consisting of patient, treatment, and tumor factors were studied and multivariate Cox proportional hazards regression was performed to identify independent predictors for survival outcome, based on which we developed clinical nomogram. The nomogram was externally validated in the validation group. Results Multivariate analysis showed that tumor size (P = 0.011) was the only factor correlated with 2-year overall survival, whereas 2-year locoregional control (LRC) was significantly related to tumor size (P = 0.024) and the maximum standardized uptake value (SUVmax) (P = 0.044), so does 2-year progression-free survival (PFS) (tumor size: P = 0.026; SUVmax: P = 0.038). Nomogram for 2-year LRC and 2-year PFS were created based on aforementioned results. The C-indexes for the nomograms to predict 2-year LRC and PFS were 0.816 and 0.804, respectively, in model group, and were 0.729 and 0.731, respectively, in the validation group. Calibration plots also showed that the model performed well. Conclusions Tumor of larger size and higher SUVmax predisposed patients to early onset of locoregional and distant progression. The nomogram developed in our study would be helpful in clinical decision-making and selection of patients who may benefit from more rigorous follow-up and aggressive systemic treatment plan.

Risk Factors Associated With Symptomatic Radiation Pneumonitis After Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer.

Radiation pneumonitis is the most frequent acute pulmonary toxicity following stereotactic body radiation therapy for lung cancer. Here, we investigate clinical and dosimetric factors associated with symptomatic radiation pneumonitis in patients with stage I non–small cell lung cancer treated with stereotactic body radiation therapy. A total of 67 patients with stage I non–small cell lung cancer who received stereotactic body radiation therapy at our institution were enrolled, and their clinicopathological parameters and dosimetric parameters were recorded and analyzed. The median follow-up period was 26.4 months (range: 7-48 months). In univariate analysis, tumor size (P = .041), mean lung dose (P = .028), V2.5 (P = .024), V5 (P = .014), V10 (P = .004), V20 (P = .024), V30 (P = .020), V40 (P = .040), and V50 (P = 0.040) were associated with symptomatic radiation pneumonitis. In multivariable logistic regression analysis, V10 (P = .049) was significantly associated with symptomatic radiation pneumonitis. In conclusion, this study found that tumor size, mean lung dose, and V2.5 to V50 were risk factors markedly associated with symptomatic radiation pneumonitis. Our data suggested that lung V10 was the most significant factor, and optimizing lung V10 may reduce the risk of symptomatic radiation pneumonitis. For both central and peripheral stage I lung cancer, rate of radiation pneumonitis ≥grade 2 was low after stereotactic body radiation therapy with appropriate fraction dose.

Clinical benefits of new immobilization system for hypofractionated radiotherapy of intrahepatic hepatocellular carcinoma by helical tomotherapy.

OBJECTIVE A comprehensive clinical evaluation was conducted, assessing the Body Pro-Lok immobilization and positioning system to facilitate hypofractionated radiotherapy of intrahepatic hepatocellular carcinoma (HCC), using helical tomotherapy to improve treatment precision. METHODS Clinical applications of the Body Pro-Lok system were investigated (as above) in terms of interfractional and intrafractional setup errors and compressive abdominal breath control. To assess interfractional setup errors, a total of 42 patients who were given 5 to 20 fractions of helical tomotherapy for intrahepatic HCC were analyzed. Overall, 15 patients were immobilized using simple vacuum cushion (group A), and the Body Pro-Lok system was used in 27 patients (group B), performing megavoltage computed tomography (MVCT) scans 196 times and 435 times, respectively. Pretreatment MVCT scans were registered to the planning kilovoltage computed tomography (KVCT) for error determination, and group comparisons were made. To establish intrafractional setup errors, 17 patients with intrahepatic HCC were selected at random for immobilization by Body Pro-Lok system, undergoing MVCT scans after helical tomotherapy every week. A total of 46 MVCT re-scans were analyzed for this purpose. In researching breath control, 12 patients, randomly selected, were immobilized by Body Pro-Lok system and subjected to 2-phase 4-dimensional CT (4DCT) scans, with compressive abdominal control or in freely breathing states, respectively. Respiratory-induced liver motion was then compared. RESULTS Mean interfractional setup errors were as follows: (1) group A: X, 2.97 ± 2.47mm; Y, 4.85 ± 4.04mm; and Z, 3.77 ± 3.21mm; pitch, 0.66 ± 0.62°; roll, 1.09 ± 1.06°; and yaw, 0.85 ± 0.82°; and (2) group B: X, 2.23 ± 1.79mm; Y, 4.10 ± 3.36mm; and Z, 1.67 ± 1.91mm; pitch, 0.45 ± 0.38°; roll, 0.77 ± 0.63°; and yaw, 0.52 ± 0.49°. Between-group differences were statistically significant in 6 directions (p < 0.05). Mean intrafractional setup errors with use of the Body Pro-Lok system were as follows: X, 0.41 ± 0.46mm; Y, 0.86 ± 0.80mm; Z, 0.33 ± 0.44mm; and roll, 0.12 ± 0.19°. Mean liver-induced respiratory motion determinations were as follows: (1) abdominal compression: X, 2.33 ± 1.22mm; Y, 5.11 ± 2.05mm; Z, 2.13 ± 1.05mm; and 3D vector, 6.22 ± 1.94mm; and (2) free breathing: X, 3.48 ± 1.14mm; Y, 9.83 ± 3.00mm; Z, 3.38 ± 1.59mm; and 3D vector, 11.07 ± 3.16mm. Between-group differences were statistically different in 4 directions (p < 0.05). CONCLUSIONS The Body Pro-Lok system is capable of improving interfractional and intrafractional setup accuracy and minimizing tumor movement owing to respirations in patients with intrahepatic HCC during hypofractionated helical tomotherapy.

105P: Risk factors associated with symptomatic radiation pneumonitis after stereotactic body radiation therapy for stage I non-small cell lung cancer

Background: Radiation pneumonitis (RP) is the most frequent acute pulmonary toxicity following stereotactic body radiation therapy (SBRT) for lung cancer. Here we investigate clinical and dosimetric factors associated with symptomatic RP in stage I non-small cell lung cancer (NSCLC) patients treated with SBRT. Methods: A total of 67 patients with stage I NSCLC who received SBRT at our institution were enrolled and their clinicopathological parameters and dosimetric parameters were recorded and analyzed. Results: The median follow-up period was 26.4 months (range, 7–48 months). In univariable analysis, tumor size (P = 0.041), mean lung dose (MLD; P = 0.028), V2.5 (P = 0.024), V5 (P = 0.014), V10 (P = 0.004), V20 (P = 0.024), V30 (P = 0.020), V40 (P = 0.040), V50 (P = 0.040) were associated with symptomatic RP. In multivariable logistic regression analysis, V10 (P = 0.049) was significantly associated with symptomatic RP. Conclusions: In conclusion, this study found that tumor size, MLD and V2.5–50 were risk factors markedly associated with symptomatic RP.V10 was the most significant factor and planning constraints should be optimized to minimize the lung dose V10.For both central and peripheral stage I lung cancer, rates of RP grade 2 was low after SBRT with appropriate fraction dose and it has no correlation with the location of radiation field. Clinical trial identification: ChiCTR-OPN-15006864 (Chinese Clinical Trial Registry) Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest.

119P: Feasibility and efficacy of helical IMRT for stage III non-small cell lung cancer in comparison with conventionally fractionated 3D-CRT

Background: Lung cancer is the 4th leading cause of death in all cancers. Adenocarcinomas of lung constitute up to 50% of NSCLC. In Pakistan like rest of the world lung cancer prevalence is high (15%) and primary lung adenocarcinoma constitute about 40–45% of primary lung cancer. Mutations in EGFR tyrosine kinase domain have been reported in adenocarcinoma. EGFR mutation screening has become imperative for the selection of metastatic NSCLC patients eligible for targeted treatment. This report presents distribution of EGFR mutations in 315 NSCLC patients. Methods: EGFR mutation in tumor samples was screened by multiplex real time PCR (Roche Diagnostics(R), USA) according to the manufacturer’s instructions. Briefly, DNA from FFPE tissue, obtained from Histopathology sections, was extracted and amplified with primers and probes specific to 43 different EGFR mutations in Cobas z 480 instrument. The assay can detect 43 mutations in four exons (18–21) of EGFR gene, including several point mutations, deletions and insertions. Results: Out of 315 patients, 208 were male and 107 were females; male to female ratio was 2:1. The mean age of the patients was 62 years and age distribution was 23 and 85 years. On the basis of immuno histopathological finding tumors were categorized into two groups; well to poorly differentiated adenocarcinoma 231(73%) and metastatic adenocarcinoma 84 (27%). EGFR mutation Del 19 was detected in 38 patients, its short in-frame deletion in exon 19, clustered around the amino acid resideus747–750(most common variant delL746-A750, delL747T751insS, and delL747-P753insS). Whereas L858R point mutation (substitution of amino acid leucine to arginine) was found in 27 patients. In two patients compound mutation, two point mutations together [S768I and G719X] and another one insertion (amino acid residues inserted) on Exon 20 was observed. L858R (exon 21) and deletion 19 exon were most frequent mutations in primary lung adenocarcinoma patients of Pakistani origin, in published literature female preponderance was significant. Conclusions: Our study showed Del 19 and L858R were the most frequent mutations in Pakistani lung cancer patients. In additions, 25% of the patients were found eligible for targeted therapy. Legal entity responsible for the study: N/A Funding: N/A Disclosure: All authors have declared no conflicts of interest.