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ORIGINAL ARTICLE
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Dose–volume analysis of acute gastrointestinal complications in cervical cancer undergoing definitive concurrent chemoradiation


 Department of Radiotherapy, RIMS, Ranchi, Jharkhand, India

Date of Submission03-May-2019
Date of Decision10-Aug-2019
Date of Acceptance23-Oct-2019
Date of Web Publication13-Oct-2020

Correspondence Address:
Rajanigandha Tudu,
SR Quarter No. 15, RIMS, Bariatu, Ranchi - 834 009, Jharkhand
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_313_19

 > Abstract 


Context: Definitive concurrent chemoradiation with brachytherapy is the prime modality of treatment of cervical cancer. The small bowel is one of the critical organs responsible for gastrointestinal complications.
Aims: This study aims to analyze the relation of small bowel dosimetric parameters with the incidence of acute gastrointestinal complications.
Subjects and Methods: The study analyzed 40 patients of stage IIB–IVA who underwent concurrent chemoradiation with three-dimensional conformal radiotherapy and weekly cisplatin from June 2017 to June 2018. The small bowel was contoured as the organ of risk. Dose–volume histogram parameters of the small bowel subjected to analysis were mean dose, maximum dose, the total volume of organ receiving 20 Gy, 40 Gy, and 45 Gy (V20-45), and the volume of V20-45 to total volume (V20-45 ratio). Gastrointestinal toxicity was graded using CTCAE version 5.0 criteria. Association between dosimetric parameters and incidence of 1–2 gastrointestinal complications were evaluated.
Results: A total of forty patients treated with concurrent chemoradiation were analyzed. Seven patients reported Grade 1, whereas three patients reported Grade 2 gastrointestinal complications. None of the patients reported Grade 3 or higher gastrointestinal complication. Patients with gastrointestinal complications had greater V30-45 and mean dose as compared to those without gastrointestinal complication.
Conclusions: Dosimetric parameters of small bowel should be evaluated to reduce the incidence of gastrointestinal complications.

Keywords: Cervical cancer, gastrointestinal toxicity, small bowel



How to cite this URL:
Kumar A, Tudu R, Singh R, Raina P. Dose–volume analysis of acute gastrointestinal complications in cervical cancer undergoing definitive concurrent chemoradiation. J Can Res Ther [Epub ahead of print] [cited 2020 Oct 20]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=298074




 > Introduction Top


Concurrent chemoradiation along with brachytherapy is the standard treatment of cervical cancer. Pelvic radiation is an integral part of the management of gynecological cancers. Radiation enteritis is known to be one of the most common complications of pelvic radiation.

Radiation enteritis is the damage to the lining of the intestines caused by radiation therapy, which is the most frequent complication of radiation therapy for cervical cancer.[1] Radiation enteritis, with symptoms of nausea, vomiting, diarrhea, pain, bleeding, and weight loss is, therefore, an almost inevitable consequence of therapeutic abdominal irradiation administered to patients with abdominal or gynecologic malignancy.[2]

The small bowel represents the most important dose-limiting structure in pelvic radiotherapy. Kavanagh noted that small bowel toxicity is likely related to maximum dose and/or volume threshold parameters qualitatively.[3]

Bowel toxicity has been mostly evaluated in postoperative cases of cervical cancer. Very few studies have been conducted for bowel toxicity in intact cervix. Therefore, this study aims to evaluate the relationship between dose–volume parameters of the small bowel and the incidence of acute gastrointestinal complications in cervical cancer patients undergoing concurrent chemoradiation.


 > Subjects and Methods Top


Patients

The study was conducted as a retrospective review of 40 patients with clinically staged IIB–IVA cervical cancer patients who underwent concurrent chemoradiation at our institute between June 2017 and June 2018. Patients were histologically proven cases of squamous cell carcinoma. Patients with a minimum follow-up of 3 months were included in the study.

Radiotherapy and chemotherapy

The patients were immobilized in the supine position and computed tomography (CT) scan was performed in a full bladder. The CT scan range was from L2 vertebral body to at least 7 cm below the bottom of obturator foramen. XiO treatment planning system was used to design the radiation fields [Figure 1] and [Figure 2]. The target volumes and organs at risk were delineated according to RTOG guidelines.[4] The clinical target volume (CTV) comprised gross visible tumors with extension, uterus, parametrium, and vagina. The regional nodal CTV consists of the common iliac, external iliac, internal iliac, and presacral lymph nodes. A margin of 1–1.5 cm around CTV in the region of uterus and cervix and 0.7 cm in the region of nodal CTV were given for PTV.
Figure 1: Four-field box three-dimensional conformal radiotherapy technique for cancer cervix

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Figure 2: Isodose lines for three-dimensional conformal radiotherapy planning of cancer cervix

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Three-dimensional conformal radiation planning was done for all patients. Dose prescription was set at 46 Gy in 23 fractions. All plans were normalized to cover 95% of PTV with 100% of the prescribed dose. 6 MV X-rays (Synergy, Elekta) were used to deliver radiation.

Patients received weekly cisplatin (40 mg/m 2), concurrently on days 1, 8, 15, and 22 of radiation.

Contouring and evaluation of organs at risk

The organs at risk contoured include the small bowel, bladder, rectum, and bilateral femoral heads. Dose–volume histogram (DVH) parameters subjected to analysis included mean dose and maximum dose to small bowel loops, V20-45 ratio, and volume of this organ. V20-45 volume means volume receiving more than the respective dose; V20-45 ratio means volume receiving more than respective dose to total volume.

Toxicity evaluation

The patients were assessed weekly by the radiation oncologist during radiation and followed up monthly on outpatient basis after radiation. Any symptom pertaining to gastrointestinal toxicity such as nausea, vomiting, colicky abdominal pain, and fecal urgency were noted and graded according to the CTCAE criteria version 5.0 (NCI, USA). Toxicity data were collected from the medical case files.

Statistical analysis

Association between selected dosimetric parameters and the incidence of gastrointestinal complications were evaluated. The relationship between clinical and dosimetric parameters with the incidence of gastrointestinal complications was analyzed with Mann–Whitney U-test for quantitative variables and Fisher's exact test for categorical variables tabulated in [Table 1]. The comparison of mean DVH parameters for small bowel loops with gastrointestinal toxicity was done by Mann–Whitney U-test.
Table 1: Univariate analysis for development of Grade 1-2 gastrointestinal complications

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 > Results Top


The pretreatment patient and tumor characteristics are shown in [Table 2]. The median age of the study population was 49.5 years. The ECOG performance status was 0–1 for all patients. The median follow-up period was 8 months (range: 4–12 months).
Table 2: Patient, tumor, and treatment characteristics

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Thirty patients had Grade 0 gastrointestinal complications. Seven patients reported Grade 1, whereas three patients reported Grade 2 complications. None of the patients reported Grade 3 or higher complications. The mean DVH parameters of small bowel loops of patients with and without gastrointestinal complications are shown in [Table 3]. Patients with gastrointestinal complications had greater V20-45 and mean dose as compared to those without gastrointestinal complications.
Table 3: Comparison of mean dose-volume histogram parameters of small bowel loops in patients with and without acute gastrointestinal complications

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 > Discussion Top


Pelvic radiotherapy is an integral part of the management of gynecological cancers. Radiation enteritis is the most common side effect of pelvic radiation manifesting in the form of colicky abdominal pain, vomiting, and diarrhea. Significant correlation has been suggested between the volume of irradiated small bowel and the likelihood of acute toxicity.[5]

Almost, all patients receiving pelvic or abdominal radiotherapy experience some form of gastrointestinal symptoms.[6] Patients usually notice these symptoms during the 2nd week of treatment (when tissue damage and inflammation is probably at a maximum), and they characteristically peak by the 4th to 5th week (when histological changes are stable or improving).[7] It was also seen in our study, where patients complained of abdominal symptoms during 2nd week of radiation. Seven patients complained of vomiting and abdominal pain in our study.

Acute gastrointestinal complications often lead to treatment interruptions. The Quantitative Analysis of Normal Tissue Effects in the Clinic review summarizes the available three-dimensional conformal radiotherapy data to update and refine the normal tissue dose/volume tolerance guidelines for small bowel, which is “the absolute volume of small bowel receiving >15 Gy should be held to <120 cc when possible to minimize severe acute toxicity <10%, if delineating the contours of bowel loops themselves.[8] Our study showed significant association of V20-45 with the incidence of gastrointestinal complications.

Studies have been conducted on radiation-induced bowel toxicity for postoperative cancer cervix, where maximum dose and V40 ratio of the small bowel loops were shown to have a significant association with chronic gastrointestinal complications.[9],[10]

The mean volume of small bowel irradiated in our study was 373.09 cc (138.87 cc–805.01 cc).

Maximum dose was seen to be associated with gastrointestinal toxicity in our study. Kavanagh had noted that small bowel toxicity is likely related to maximum dose and volume threshold parameters.[3]

Chemotherapy also increases the risk of gastrointestinal toxicity. Only 20% of the patients of our study completed all four cycles of weekly concurrent chemotherapy.

This study has limitations of a small sample size. Being a retrospective study, the toxicity data and grading variability were observer dependent.


 > Conclusions Top


Acute radiation enteritis is one of the most common side effects of pelvic radiation affecting treatment compliance and hampers the quality of life. Dosimetric parameters of small bowel irradiated should be taken into consideration to decrease the incidence of radiation enteritis. Further, studies should be conducted to evaluate the dose–volume relationship of the small bowel and gastrointestinal toxicities.

Acknowledgment

We are thankful to the radiation oncology department.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Czito BG, Willett CG. Radiationinjury. In: Feldman M, Friedman LS, Brandt LJ, editors. Sleisenger and Fordtran's Gastrointestinal and Liver Disease. 9th ed., Ch. 39. Philadelphia, PA: Saunders Elsevier; 2010.  Back to cited text no. 1
    
2.
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. 2
    
3.
Kavanagh BD, Pan CC, Dawson LA, Das SK, Li XA, Ten Haken RK, et al. Radiation dose-volume effects in the stomach and small bowel. Int J Radiat Oncol Biol Phys 2010;76:S101-7.  Back to cited text no. 3
    
4.
Small W Jr. Mell LK, Anderson P, Creutzberg C, De Los Santos J, Gaffney D, et al. Consensus guidelines for delineation of clinical target volume for intensity-modulated pelvic radiotherapy in postoperative treatment of endometrial and cervical cancer. Int J Radiat Oncol Biol Phys 2008;71:428-34.  Back to cited text no. 4
    
5.
Martin E, Pointreau Y, Roche-Forestier S, Barillot I. Normal tissue tolerance to external beam radiation therapy: Small bowel. Cancer Radiother 2010;14:350-3.  Back to cited text no. 5
    
6.
Andreyev J. Gastrointestinal symptoms after pelvic radiotherapy: A new understanding to improve management of symptomatic patients. Lancet Oncol 2007;8:1007-17.  Back to cited text no. 6
    
7.
Khalid U, McGough C, Hackett C, Blake P, Harrington KJ, Khoo VS, et al. A modified inflammatory bowel disease questionnaire and the Vaizey incontinence questionnaire are more sensitive measures of acute gastrointestinal toxicity during pelvic radiotherapy than RTOG grading. Int J Radiat Oncol Biol Phys 2006;64:1432-41.  Back to cited text no. 7
    
8.
Marks LB, Yorke ED, Jackson A, Ten Haken RK, Constine LS, Eisbruch A, et al. Use of normal tissue complication probability models in the clinic. Int J Radiat Oncol Biol Phys 2010;76:S10-9.  Back to cited text no. 8
    
9.
Chen Z, Zhu L, Zhang B, Meng M, Yuan Z, Wang P. Dose-volume histogram predictors of chronic gastrointestinal complications after radical hysterectomy and postoperative intensity modulated radiotherapy for early-stage cervical cancer. BMC Cancer 2014;14:789.  Back to cited text no. 9
    
10.
Isohashi F, Yoshioka Y, Mabuchi S, Konishi K, Koizumi M, Takahashi Y, et al. Dose-volume histogram predictors of chronic gastrointestinal complications after radical hysterectomy and postoperative concurrent nedaplatin-based chemoradiation therapy for early-stage cervical cancer. Int J Radiat Oncol Biol Phys 2013;85:728-34.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

 
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