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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 14  |  Issue : 1  |  Page : 36-39

Use of simultaneous radiation boost achieves high treatment response rate in patients with metastatic gastric cancer


The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, China

Date of Web Publication8-Mar-2018

Correspondence Address:
Prof. Jing Yan
The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_387_17

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 > Abstract 

Objective: Intensity-modulated radiation therapy (IMRT) with a simultaneous integrated boost (SIB) could improve local control rates at different anatomic sites. However, little is known for its use in metastatic gastric cancer. Our study aimed to compare the treatment response rates of IMRI-SIB and conformal radiotherapy (CRT) in patients with metastatic gastric cancer.
Materials and Methods: We retrospectively identified twenty patients with metastatic gastric cancer from 2013 to 2015, 12 given IMRT-SIB, and eight given CRT. Treatment response and toxicities were evaluated for all patients. The radiation target included peritoneal lymph nodes. RECIST criteria were used to assess the treatment response. Three patients of eight in the CRT group died before the end of treatment due to the progression of diseases in the field.
Results: For the IMRT-SIB group, the median dose of high dose field was 60.8 Gy (50–64.4 Gy), and the median dose of low-dose field was 45 Gy (36–50.4 Gy). For the CRT group, the median dose of the total dose was 50 Gy (41.4–60 Gy). IMRT-SIB could elevate local dose significantly, compared to the CRT group. One patient of 12 in the IMRT-SIB group achieved complete response, and nine patients achieved partial response (PR), whereas no patient achieved CR in the CRT group. Two of five patients achieved PR (40%) in the CRT group. IMRT-SIB improved the treatment response rate significantly (odds ratio 8.33, 95% confidence interval: 1.03–67.14, P = 0.046). Two patients of 12 in the IMRT-SIB group developed enteritis, whereas two patients of five developed enteritis in the CRT group.
Conclusions: IMRT-SIB could escalate the local dose and improve the treatment response rates in patients with metastatic gastric cancer and with acceptable toxicities. Further study with a larger population to validate our data is underway.

Keywords: Conformal radiotherapy, intensity-modulated radiation therapy-simultaneous integrated boost, metastatic gastric cancer, treatment response


How to cite this article:
Yang J, Liu J, Gao S, Yang Y, Kong W, Ren W, Zhu L, Yang M, Wei J, Zou Z, Qian X, Liu B, Yan J. Use of simultaneous radiation boost achieves high treatment response rate in patients with metastatic gastric cancer. J Can Res Ther 2018;14:36-9

How to cite this URL:
Yang J, Liu J, Gao S, Yang Y, Kong W, Ren W, Zhu L, Yang M, Wei J, Zou Z, Qian X, Liu B, Yan J. Use of simultaneous radiation boost achieves high treatment response rate in patients with metastatic gastric cancer. J Can Res Ther [serial online] 2018 [cited 2019 Jul 21];14:36-9. Available from: http://www.cancerjournal.net/text.asp?2018/14/1/36/226740


 > Introduction Top


About 80%–90% of patients with gastric cancer present with locally advanced or metastatic tumors that have poor rates of resectability.[1] Palliative resection and radiotherapy are local regional treatment options to manage the metastatic gastric disease and frequently used to palliate pain, obstruction, and bleeding from gastric tumors. Radiation was an effective and well-tolerated modality to improve the symptoms of the patients with locally advanced or recurrent gastric cancer.[2] Chemoradiation for patients with obstructive jaundice resulting from extrahepatic biliary metastases from gastric carcinoma could achieve satisfactory palliation and improve the quality of life.[3] However, treatment-related toxicities should be taken into account for the patients at the very late stage. For instance, radiation-induced enteritis could produce symptoms such as pain, bloating, nausea, diarrhea, steatorrhoea, and malabsorption of selected or multiple nutrients.[4]

Use of modern imaging and radiotherapy techniques minimizes the radiation exposure to normal tissues. Intensity-modulated radiation therapy (IMRT) is widely used worldwide, due to its ability to create multiple targets and multiple avoidance structures. This technology can deliver radiation more precisely to the tumor while relatively spare the surrounding normal tissues. IMRT was shown to minimize acute treatment-related morbidity and achieve dose escalation.[5] Simultaneous integrated boost (SIB) technique based on the IMRT technology delivers various fraction doses to different target volumes in a single-phase plan. IMRT with a SIB (IMRT-SIB) could improve local control rates at different anatomic sites.[6],[7],[8]

However, little is known for the use of IMRT-SIB in metastatic gastric cancer. To address this gap, our study retrospectively analyzed the treatment response rates and treatment-related toxicities in patients with metastatic gastric patients receiving palliative IMRT-SIB or traditional three-dimensional conformal radiotherapy (CRT).


 > Patients and Methods Top


Patients

We retrospectively analyzed twenty patients with metastatic gastric cancer ineligible or refused to receive palliative surgery from 2013 to 2015. The irradiation sites were peritoneal lymph nodes. Indications for the palliative radiotherapy included metastases-related severe abdominal pain and obstructive jaundice. After the year of 2014, patients started to receive IMRT-SIB. Twelve of twenty patients received IMRT-SIB and eight received CRT. The goal of the palliative radiotherapy was to relieve symptoms. Dose exposures to the organ at risk (OAR) including small intestine, stomach, colon, kidney, and spinal cord were evaluated for each treatment plan. The treatment response was assessed 1 month later after the treatment end by abdominal computed tomography (CT) with contrast. Written consents for all the enrolled patients were obtained before the treatment. RECIST criteria were used to assess the treatment response.

Statistical analysis

Chi-square tests were used to test for potential differences in distributions. Potential associations between the use of IMRT-SIB and treatment response were tested with a logistic regression model. All tests were two-sided and differences were considered significant at P < 0.05.


 > Results Top


Clinical characteristics

As shown in [Table 1], the IMRT-SIB group included 12 patients with metastatic gastric cancer and half of them were female, and the CRT group included eight patients and three of them were male. The gender distribution between two groups showed no significant differences (P = 0.670). The median age of the IMRT-SIB group and the CRT group was 56 and 56.3 years old, respectively. The difference was not significant, either (P = 0.686). The median planning target volume (PTV) was 368.23 cm 3 for the IMRT-SIB group and 324.64 cm 3 for the CRT group. No differences between PTV of these two groups were shown (P = 0.168). The median doses of the IMRT-SIB group and the CRT group were 60.8 and 50 Gy, respectively. The IMRT-SIB could escalate the total dose by approximately 20% (P = 0.032), compared to the CRT group.
Table 1: Clinical characteristics of the studied population

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OAR included intestine, kidney, liver, and spinal cord. Doses for OAR were evaluated. The max exposure dose (Dmax) was evaluated for the intestine. As shown in [Table 1], the median Dmax of intestine for the IMRT-SIB and CRT group was 48.31 and 40.32 Gy, respectively. The difference was not significant (P = 0.892). Similar to the intestine, IMRT-SIB did not elevate the dose for kidney, liver, and spinal cord, either [Table 1]. As shown in [Figure 1], the treatment plan for the same patient was simulated using IMRT-SIB and CRT, respectively. Radiation dose exposed to the normal tissue did not increase obviously in the IMRT-SIB group, compared to the CRT.
Figure 1: Dose comparison between intensity-modulated radiation therapy-simultaneous integrated boost and conformal radiotherapy

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Potential associations between the use of intensity-modulated radiation therapy-simultaneous integrated boost and treatment responses or toxicities

Treatment responses were evaluated 1 month after the treatment end by the use of contrast CT. For the CRT group, three patients died before the treatment end. In the IMRT-SIB group, one patient achieved complete response, eight patients' partial response (PR), and only two patients had stable disease [Table 2]. For the CRT group, only two patients achieved PR. Compared to the CRT group, the use of IMRT-SIB could improve the treatment response rate significantly (odds ratio [OR]: = 8.33, 95% confidence interval [CI]: 1.03–67.14, P = 0.046). Besides, symptoms of most patients in the IMRT-SIB group relieved apparently after the treatment.
Table 2: The association of the use of intensity-modulated radiation therapy-simultaneous integrated boost and treatment responses

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Due to the dose exposure to the small intestine, enteritis is the common toxicity for the abdominal radiotherapy. In the CRT group, two patients developed enteritis, whereas one patient developed enteritis in the IMRT-SIB group. The use of IMRT-SIB could escalate the irradiation dose substantially; however, IMRT-SIB did not increase the risk of treatment-related toxicities (OR = 0.273, 95% CI: 0.020–3.666, P = 0.327) [Table 3].
Table 3: The association of the use of intensity-modulated radiation therapy-simultaneous integrated boost and the risk of enteritis

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 > Discussion Top


Our results indicated that the use of IMRT-SIB could escalate the radiation dose, improve the treatment response rates, and relieve the symptoms of patients significantly, without increased risk of treatment-related toxicities. IMRT-SIB could be a promising treatment modality for the patients with metastatic gastric cancer to improve the quality of life.

Recently, some studies had the similar results to the present study. Swanick et al. identified 71 patients with nonsmall cell lung cancer (NSCLC) receiving IMRT-SIB in the University of Texas MD Anderson Cancer Center. Their study suggested that IMRT + SIB is a viable option for some patients with NSCLC, with little high-grade toxicity overall.[7] Another study by Welsh et al. included 44 patients with unresectable esophageal cancer and their results demonstrated that SIB-IMRT to gross primary disease might improve local control for patients with unresectable locally advanced esophageal cancer, especially those with adenocarcinoma.[6] Different from the studies above, which tried to deliver the definitive treatment to patients, our study aimed to ease the pain and tumor burden for the patients with metastatic gastric cancer. As far as we know, this is the first study investigating roles of IMRT-SIB in patients with metastatic gastric cancer.

There are some potential advantages that patients could benefit from the use of IMRT-SIB. This regimen elevated the dose per fraction and therefore increased the biologically effective dose. Relatively higher dose per fraction could modulate tumor phenotypes, enhance antigen presentation and tumor immunogenicity, and increase production of cytokines and alter the tumor microenvironment, enabling the destruction of the tumor by the immune system.[9] Second, the use of IMRT-SIB could potentially shorten the treatment time, and this will be helpful for patients who are already deconditioned and unable to complete the conventional treatment.

Our study also has some limitations, chiefly its retrospective and single-institution nature. Second, the study sample size is small. Only twenty patients were included in our study. Based on our study, prospective clinical trials with larger sample size from multiple-institution will be applied to validate our results.


 > Conclusion Top


Our study found that the use of IMRT-SIB could escalate the radiation dose and improve the treatment response rate substantially and without increased risk of toxicities in patients with metastatic gastric cancer. IMRT-SIB may be a viable option for patients with metastatic gastric cancer to relieve the suffering symptoms and improve the quality of life.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

1.
Dicken BJ, Bigam DL, Cass C, Mackey JR, Joy AA, Hamilton SM, et al. Gastric adenocarcinoma: Review and considerations for future directions. Ann Surg 2005;241:27-39.  Back to cited text no. 1
    
2.
Tey J, Back MF, Shakespeare TP, Mukherjee RK, Lu JJ, Lee KM, et al. The role of palliative radiation therapy in symptomatic locally advanced gastric cancer. Int J Radiat Oncol Biol Phys 2007;67:385-8.  Back to cited text no. 2
    
3.
Lo SS, Wu CW, Chi KH, Tseng HS, Shen KH, Hsieh MC, et al. Concomitant chemoradiation treatment in the management of patients with extrahepatic biliary tract recurrence of gastric carcinoma. Cancer 2000;89:29-34.  Back to cited text no. 3
    
4.
Stacey R, Green JT. Radiation-induced small bowel disease: Latest developments and clinical guidance. Ther Adv Chronic Dis 2014;5:15-29.  Back to cited text no. 4
    
5.
Teh BS, Woo SY, Butler EB. Intensity modulated radiation therapy (IMRT): A new promising technology in radiation oncology. Oncologist 1999;4:433-42.  Back to cited text no. 5
    
6.
Welsh JW, Seyedin SN, Allen PK, Hofstetter WL, Ajani JA, Chang JY, et al. Local control and toxicity of a simultaneous integrated boost for dose escalation in locally advanced esophageal cancer: Interim results from a prospective phase I/II trial. J Thorac Oncol 2017;12:375-82.  Back to cited text no. 6
    
7.
Swanick CW, Lin SH, Sutton J, Naik NS, Allen PK, Levy LB, et al. Use of simultaneous radiation boost achieves high control rates in patients with non-small-cell lung cancer who are not candidates for surgery or conventional chemoradiation. Clin Lung Cancer 2015;16:156-63.  Back to cited text no. 7
    
8.
Peponi E, Glanzmann C, Kunz G, Renner C, Tomuschat K, Studer G, et al. Simultaneous integrated boost intensity-modulated radiotherapy (SIBIMRT) in nasopharyngeal cancer. Strahlenther Onkol 2010;186:135-42.  Back to cited text no. 8
    
9.
Bernstein MB, Krishnan S, Hodge JW, Chang JY. Immunotherapy and stereotactic ablative radiotherapy (ISABR): A curative approach? Nat Rev Clin Oncol 2016;13:516-24.  Back to cited text no. 9
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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