Application of radiomics approach for decoding normal liver features and predicting chemotherapy-associated liver injury:A preliminary study / 中国癌症杂志

Background and purpose:Radiomics refers to the comprehensive quantification of human tissues through assessing a large number of quantitative image features. Radiomics approach is used to decode tumor phenotypes and predict treatment outcomes. Here we present a study investigating radiomic analysis to assess normal liver features and predict chemotherapy-associated liver injury.Methods:Gastric cancer patients treated with surgery and adjuvant chemotherapy were enrolled in this study retrospectively. CT images were obtained before chemotherapy. The whole liver organ was delineated by radiation oncologists. Images were extracted and filtered by radiomic approach to extract radiomic features. Clustering was performed to reveal clusters of patients with similar radiomic expression patterns. Chi-squared tests were used to assess the association of radiomic data with clinical data and chemotherapy-related liver injury.Results:Radiomic features of 73 patients were clustered into two clusters. A significant association with gender (P=0.004, chi-squared test) was observed, where in male showed a higher presence in cluster Ⅰ. Incidence of abnormal liver function after chemotherapy was 48.7% in cluster I and 67.6% in cluster Ⅱ, respectively (Δ=18.9%). Clinical data including age, gender, chemotherapy modality, number of chemotherapy cycles, HBV infection history, HBs-antigen presence were not associated with liver function abnormalities after chemotherapy. Accuracy of radiomic analysis to predict liver injury is 0.59.Conclusion:Radiomic approach revealed different imaging features of liver between men and women. It could help to predict chemotherapy-associated liver injury. It is feasible to use radiomics approach to decode normal liver features and predict treatment-associated liver injury.

Research progress of radiotherapy and molecular classifications of gastric cancer / 中国医师杂志

Adjuvant radiotherapy (RT) can improve the rate of loco-regional control for patients with gastric cancer (GC),while the selection of patients plays a key role.As the research moves along,several relatively comprehensive molecular classifications emerged such as the TCGA classification and the ACRG classification.Studies have demonstrated that molecular classifications are closely related to the clinicopathologic characteristics,prognosis and treatment response.However,there is not recognized molecular classification of GC presently.It is a great challenge for radiation oncologists to make use of the individual bioinformation and accurately select patients who would benefit from RT.Meanwhile,precision RT could also be achieved with the prediction of radiosensitivity,combination of RT with targeted therapy and the application of ctDNA within the field of RT.

Research progress in molecular classification of gastric cancer / 中华胃肠外科杂志

Gastric cancer(GC) is a highly heterogeneous malignancy. The present widely used histopathological classifications have gradually failed to meet the needs of individualized diagnosis and treatment. Development of technologies such as microarray and next-generation sequencing (NGS) has allowed GC to be studied at the molecular level. Mechanisms about tumorigenesis and progression of GC can be elucidated in the aspects of gene mutations, chromosomal alterations, transcriptional and epigenetic changes, on the basis of which GC can be divided into several subtypes. The classifications of Tan's, Lei's, TCGA and ACRG are relatively comprehensive. Especially the TCGA and ACRG classifications have large sample size and abundant molecular profiling data, thus, the genomic characteristics of GC can be depicted more accurately. However, significant differences between both classifications still exist so that they cannot be substituted for each other. So far there is no widely accepted molecular classification of GC. Compared with TCGA classification, ACRG system may have more clinical significance in Chinese GC patients since the samples are mostly from Asian population and show better association with prognosis. The molecular classification of GC may provide the theoretical and experimental basis for early diagnosis, therapeutic efficacy prediction and treatment stratification while their clinical application is still limited. Future work should involve the application of molecular classifications in the clinical settings for improving the medical management of GC.

Prediction of efficacy of neoadjuvant radiochemotherapy based on depth of invasion in T3 rectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the association of mesorectal invasion depth before neoadjuvant radiochemotherapy with pathological outcome and to provide evidence for individualized treatment in T3 rectal cancer.</p><p><b>METHODS</b>Retrospective analysis was performed on the clinical records of 73 consecutive rectal cancer patients treated with neoadjuvant radiochemotherapy and radical surgery in the Shanghai Cancer Center from January 2010 to December 2012. All the patients underwent high-resolution MRI and the depth of mesorectal invasion, lymph node status, tumor length, and mesorectal fascia status were evaluated. The category T3 was subdivided according to the measurement of the maximal tumor invasion beyond the outer border of the muscularis propria: T3a(<5 mm), T3b(5-10 mm) and T3c(>10 mm). The association of mesorectal invasion depth,other MRI and clinical features with short-term efficacy was analyzed,especially with pathological complete response(pCR).</p><p><b>RESULTS</b>T3a, T3b and T3c accounted for 19.2%, 64.4% and 16.4% in 73 rectal cancer patients who underwent high resolution MRI, respectively. There were 42.9% of T3a patients achieved pathological complete response,significantly higher than those of T3b(14.9%)and T3c(0%) (P=0.017).</p><p><b>CONCLUSIONS</b>T3a rectal cancer patients are more likely to achieve pCR than those of T3b and T3c after neoadjuvant radiochemotherapy. The maximal tumor invasion beyond the outer border of the muscularis propria less than 5 mm may act as a predictive factor and guide the follow-up treatment of T3 rectal cancer.</p>

A clinical study to evaluate the toxicities of adjuvant chemoradiotherapy in early stage after low-anterior resection for locally advanced rectal cancer / 中华放射肿瘤学杂志

Objective In the previous study completed in Korea, early three-dimensional conformal radiotherapy concurrent with chemotherapy in rectal cancer after radical surgery demonstrated a better prognosis compared with late radiotherapy. However, with the report of MOSAIC trial, the adjuvant chemotherapy regimen had transferred from 5-Fu alone to combined 5-Fu and Oxaliplatin. We need more evidence to clarify the best radiotherapy timing during the whole period of adjuvant therapy . Methods Patients who met the following criteria were accrued in this study: 18-70 years old, lower anterior resection,pathologically proven rectal adenocarcinoma, stage T3-4 and/or N+, no evidence of distant metastases and KPS≥70. Three dimensional conformal Radiotherapy was started at the fourth week after surgery, which included 45 Gy whole pelvic radiation following by 6-10 Gy tumor bed boost. Oxaliplatin of 50 mg/m2 weekly and Xeloda 625 mg/m2 twice a day, every week from d1-5 were used concurrent with radiotherapy.Toxicity was evaluated and graded by common toxicity critera version 3. 0. The study was designed as Simon two-phase design, in the first phase, a total of 15 patients were accrued, and if more than or equal to 9 patients had grade 3 toxicity, we had 85% power to confirm the toxicity caused by early radiotherapy more than 50%. Otherwise, another 15 patients of the second phase were accrued, we would have 85% power to confirm the high toxicity of more than 50% if 18 out of 30 patients had grade 3 toxicity. Results From July 2008 to December 2008, 15 patients were treated with early radiotherapy concurrent with combined chemotherapy, Grade 3 gastrointestinal toxicity occurred in 12 patients and Grade 3 hematologic toxicity occurred in 2 patients. According to Simon design, we had 85% power to confirm the toxicity caused by early radiotherapy more than 50%. Conclusions For locally advanced rectal cancer patients, whole pelvic radiotherapy concurrent with oxaliplatin and xeloda had severe toxicities. Further studies are needed to decrease toxieities.

The impact of respiratory motion and active breathing control on the displacement of target area in patients with gastric cancer treated with post-operative radiotherapy / 中华放射肿瘤学杂志

Objective To assess the impact of respiratory motion on the displacement of target area and to analyze the discrimination between free breathing and active breathing control (ABC) in patients with gastric cancer treated with post-operative radiotherapy. Methods From January 2005 to November 2006, 22 patients with post-operatively confirmed gastric cancer were enrolled in this study. All diseases were T_3/ N +, staging Ⅱ - Ⅳ. Patients were CT scanned and treated by radiation with the use of ABC. Image J software was used in image processing, motion measurement and data analysis. Surgical clips were implanted as fiducial marks in the tumor bed and lymphatic drainage area. The motion range of each clip was measured in the resultant-projection image. Motions of the clips in superior-inferior (S-I), right-left (R-L) and anterior-posterior (A-P) directions were determined from fluoroscopy movies obtained in the treatment position. Results The motion ranges in S-I, R-L and A-P directions were 11.1 mam, 1.9 mm and 2.5 mm (F = 85.15, P = 0. 000) under free breathing, with 2.2 mm, 1.1 mm and 1.7 nun under ABC (F = 17.64, P = 0. 000), and the reduction of motion ranges was significant in both S-I and A-P directions (t = 4.36, P = 0. 000;t = 3.73,P = 0.000). When compared with under free-breathing, the motion ranges under ABC were kept unchanged in the same breathing phase of the same treatment fraction, while significant increased in different breathing phase in all three directions (t = - 4.36, P = 0. 000; t = - 3.52, P = 0.000; t =-3.79, P = 0. 000), with a numerical value of 3.7 mm, 1.6 mm and 2.8 mm, respectively (F = 19.46, P = 0. 000) . With ABC between different treatment fractions , the maximum displacements were 2.7 mm, 1.7 mm and 2.5 mm for the centre of the clip cluster (F =4.07,P =0. 019), and were 4.6 mm, 3.1 mm and 4.2 mm for the clips (F =5.17 ,P =0.007). The motion ranges were significant increased in all the three directions (t = - 4.09, P=0.000 ; t =-4.46, P = 0.000 ; t = - 3.45, P =0.000). Conclusions In the irradiation of post-operative gastric cancer, the maximum displacement of organ motions induced by respiration is in S-1 direction and the minimum in R-L direction under free breathing. The use of ABC can reduce the motions significantly in S-I and A-P directions, and the same changes exist in both inter-and intra-fraction treatment.

Comparison of dosimetry distribution between three-dimension conformal and intensity modulated plan integrated with breath motion in postoperative radiation of gastric cancer / 中华放射肿瘤学杂志

Objective To compare the dose distribution of the target and normal tissues in gastric cancers between three-dimension conformal radiation therapy (3DCRT) and intensity modulated radiation therapy (IMRT) plan when respiratory motion factors integrated in the plan. Methods From January 2005to November 2006, 10 patients with post-operatively radiation of gastric cancer were enrolled in this study.Planning CT were acquired conventionally with free-breath mode and the static treatment plans of the 3DCRT and IMRT were designed respectively. Probability distribution functions (PDF) were generated and convoluted with the static dose distributions from 3DCRT and IMRT plans to obtain the integrated plans. The dose distributions of the target and normal tissues were compared between 3DCRT and IMRT integration treatment plans, such as V45 of clinical target volume, V4o of liver and V15, V18 of left and right kidney.Results In the respiratory integrated treatment planning, the target volume coverage and homogeneity with IMRT are superior to those with 3DCRT ( ( V45 98%∶ 87% (t = -3. 35 ,P =0. 010) ,mean dose 46. 81 Gy ±0. 75 Gy∶45.99 Gy ± 1.12 Gy (t = -0. 31 ,P=0. 020) ). The V40 of teh liver in IMRT are smaller than those in 3DCRT ( 12%∶ 16% ;t=3.75,P=0.010). For the left kidney, the V15 and V18 in IMRT are smaller than those in 3DCRT ( (34%∶ 50% (t = 2. 17 ,P = 0. 050) and 27%∶46% (t = 3. 11 ,P = 0. 020) ),but for the right kidney, V15 and V18 in 3DCRT are smaller than those in IMRT ( ( 15%∶ 21% (t = - 2. 42,P=0.040) and 11%∶15% (t= -2.71,P=0.030)). Conclusions When respiratory motion factor integrated in the treatment plan, IMRT showed advantage both in target coverage and normal tissue sparing in the high dose region of liver and left kidney.

Toxicity and efficacy of post-operative chemoradiotherapy for gastric cancer / 中华放射肿瘤学杂志

Objective To evaluate the toxicity and efficacy of post-operative chemoradiotherapy for gastric cancer. Methods Forty-five gastric cancer patients treated with post-operative radiation ± concurrent chemotherapy were retrospectively analyzed. Among them, 14 were female and 31 were male. The median age was 54 (30-72) years. Pathology stages were IB-IV. Radiotherapy of doses from 45 Gy/25fx to 55 Gy/30fx was delivered to the tumor bed and regional lymph nodes with 3D conformal or IMRT technology.Concurrent chemotherapy agent was fluorouracil or capacitabine. Results All patients except 2 (4%)completed radiotherapy as planned. The most common acute toxicities were hematologic and gastrointestinal effects. The incidence of the patients was 56% with mild nausea/vomiting,71% and 7% with grade Ⅰ / Ⅱ and Ⅲ leucopenia, and 38% with grade Ⅰ/Ⅱ hypodynamia and anepithymia. The 1-year overall survival,relapse-free survival and local control rates were 87% ,82% and 95%, respectively. Conclusions Postoperative chemoradiation for patients with locally advanced gastric cancer is tolerable. Our study shows the advantage of post-operative chemoradiation for local control. However,further prospective randomized trial is needed to validate the efficacy.