|Year : 2020 | Volume
| Issue : 2 | Page : 62-66
Dose received by external genital organs during preoperative radiotherapy for rectal cancer patients
Jyotiman Nath, Gautam Sarma, Bhaveshwar Yadav, Partha Pratim Medhi, Apurba Kumar Kalita, Mouchumee Bhattacharyya
Department of Radiation Oncology, Dr. B. Borooah Cancer Institute, Guwahati, Assam, India
|Date of Submission||16-Apr-2020|
|Date of Acceptance||17-May-2020|
|Date of Web Publication||23-Jun-2020|
Dr. Gautam Sarma
Department of Radiation Oncology, Dr. B. Borooah Cancer Institute, Guwahati, Assam
Source of Support: None, Conflict of Interest: None
Introduction: Preoperative radiotherapy, followed by surgery, is a commonly used approach for locally advanced rectal and colorectal cancer. The external genitalia receive a certain dose of radiation, which may be attributed to long-term sexual dysfunction in these patients. The aim of this study is to find out the dose received by external genital organs in rectal cancer patients receiving preoperative radiotherapy. Materials and Methods: Retrospectively 25 computed tomography (CT) sets of consecutive rectal cancer patients who received preoperative radiotherapy were included. External genital organ contouring was done as per the proposed guidelines given by Brooks et al. Standard radiotherapy plans with three-field wedged portal were run in all the CT sets using 6 MV photons in eclipse treatment planning system (TPS). The total dose prescribed was 50.4 Gy in 28 daily fractions. Dose received by external genitalia were recorded. Results: Various dose-volume histogram (DVH) parameters relating to the dose received by the genitalia were recorded. In the case of male patients, there was no statistically significant difference of values in between supine and prone position except for V40 (%), P = 0.027. In the case of female patients, various DVH values are almost the same in both supine and prone positions (P > 0.05). Conclusion: External genital organs receive a significant radiation dose when treated with standard three-field wedged technique. Therefore, we suggest that the young, sexually active patients may be treated with better conformal techniques to reduce the radiation dose received by the external genitals as low as possible.
Keywords: External genitalia, preoperative radiotherapy, rectal cancer, sexual morbidity
|How to cite this article:|
Nath J, Sarma G, Yadav B, Pratim Medhi P, Kumar Kalita A, Bhattacharyya M. Dose received by external genital organs during preoperative radiotherapy for rectal cancer patients. J Radiat Cancer Res 2020;11:62-6
|How to cite this URL:|
Nath J, Sarma G, Yadav B, Pratim Medhi P, Kumar Kalita A, Bhattacharyya M. Dose received by external genital organs during preoperative radiotherapy for rectal cancer patients. J Radiat Cancer Res [serial online] 2020 [cited 2020 Oct 30];11:62-6. Available from: https://www.journalrcr.org/text.asp?2020/11/2/62/287446
| Introduction|| |
Rectal carcinoma is one of the common cancers worldwide, although with low reported cases in India. Worldwide overall colorectal cancer (CRC) ranks third in terms of incidence but second in terms of mortality. More than half of CRC incidence occurs in developed countries; however, mortality is higher in the less developed countries due to inadequate resources and health infrastructure. The age-standardized rate for CRC in India is 7.2/100,000 population in males and 5.1/100,000 population in women. Although CRC is considered to be a disease of the elderly, studies have reported a rise in the disease among young adults.,
Preoperative radiotherapy has resulted in improved outcomes in locally advanced rectal cancer patients. Improved long-term survival has led to attention toward various late side effects. Gastrointestinal disorders, neurological problems, anal dysfunction, urinary abnormality, pelvic or hip fractures, thromboembolic diseases are well documented in the literature; however, sexual dysfunction as late side effects in this group of patients has not gained much attention.,,
Various sexual morbidities that are attributed to preoperative radiotherapy in the management of rectal carcinoma are erectile dysfunction, ejaculation disorders like retrograde ejaculation in males. In the case of females, specific sexual dysfunctions include decreased libido, painful intercourse, changes in genital arousal, lubrication and altered orgasms, etc.,, In Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC), data of many organs at risk were discussed, but only the penile bulb is discussed among genital structures.
The aim of this study is to find out the dose received by external genital organs in rectal cancer patients receiving preoperative radiotherapy.
The findings of this study will help to choose the appropriate technique to reduce genital dose in rectal carcinoma patients undergoing preoperative radiotherapy.
| Materials and Methods|| |
Retrospectively 25 computed tomography (CT) sets of consecutive rectal cancer patients who received preoperative radiotherapy in Dr B Borooah Cancer Institute were included. External genital organ contouring was done as per the proposed guidelines given by Brooks et al. As per this proposed guideline, the contour of external genitalia was made by outlining the clitoris, labia majora and minora for females and the scrotum, perineal body, corpus cavernosum penis for males. For both the genders, the tissue anterior to the pubic symphysis and the surrounding fat was delineated while muscle and bones were excluded during contouring.
Standard three fields (one anterior-posterior and two-wedged lateral) were used. This is a common standard radiotherapy technique used in centers treating large numbers of patients in India. The plans were run in all the CT sets using 6 MV photons in eclipse TPS. The total dose prescribed was 50.4 Gy in 28 daily fractions (180 cGy/fraction). The dose received by external genitalia was recorded.
Bar diagram with standard deviation is used to describe the descriptive statistics. Data were checked for normality using Kolmogorov-Smirnova and Shapiro–Wilk test. Independent t-test is used depending on the fulfillment of normality assumption for mean difference. All data were analyzed using IBM SPSS Statistics for Windows, version 21 (IBM Corp., Armonk, N.Y., USA). A P < 0.05 is considered as statistically significant at 5% level of significance.
| Results|| |
Out of the 25 CT sets of patients (n = 25) who had already received preoperative radiotherapy; 14 (56%) were of male patients and 11 (44%) were of female patients. The most commonly prone position is preferred to simulate rectal cancer patients as the target volume of the disease is located posteriorly. In our study seven patients (28%) were simulated in the supine position and 18 patients (72%) were simulated in the prone position.
Various dose-volume histogram (DVH) parameters in relation to the external genital contour were recorded. [Table 1] and [Figure 1] show DVH parameters of the male patients both in supine and prone position and [Table 2] and [Figure 2] shows DVH parameters of the female patients both in supine and prone position.
|Table 1: Various dose volume histograms parameters of the male patients in both supine and prone position|
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|Figure 1: Various dose volume histogram parameters in case of male patients|
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|Table 2: Various dose volume histograms parameters of the male patients in both supine and prone position|
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|Figure 2: Various dose volume histogram parameters in case of female patients|
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It is seen that in case of male patients, the external genitalia received more radiation therapy (RT) dose in the supine position as compared to the prone position, but there is no statistically significant difference in terms of various DVH parameters except for V40 Gy; where supine patients received more dose as compared to prone patients (P = 0.027). Maximum dose to the external genitalia in both the supine and prone patients is almost equal, but the mean dose in the supine position is higher than the prone position; however not statistically significant (P = 0.124 and 0.258, respectively).
However in the case of female patients, it has been observed that various DVH values such as V20 Gy, V30 Gy, V40 Gy, V50 Gy, Max dose (Gy), Mean dose (Gy) are almost same in both supine and prone positions (P > 0.05).
| Discussion|| |
The evidence of preoperative radiotherapy for rectal cancer started growing in the late 1980s and during the 1990s. In the pre Total Mesorectal Excision (TME) era, the Swedish Rectal Cancer Trial showed a significant benefit of neoadjuvant irradiation (short-course radiotherapy of 5 × 5 Gy,) compared to surgery alone in terms of overall survival and local recurrence rate. In the post TME era, Dutch trial and the MRC CR07 trial showed the benefit of adding radiotherapy before surgery in rectal cancer patients., Alternative to short-course radiotherapy, the German CAO/ARO/AIO-94 trial introduced long course radiotherapy along with concurrent chemotherapy (CRT) and demonstrated significant improvements in local control, acute and long-term toxicity, and sphincter preservation with preoperative chemoradiotherapy in both the initial and long-term follow-up report., Although statistically not significant, in the Trans-Tasman Radiation Oncology Group (TROG) trial preoperative long-course chemoradiotherapy group has a lower cumulative local recurrence rate at 2 years and 5 years in comparison to short-course RT.
Currently, preoperative long-course radiotherapy 50.4 Gy (1.8 Gy in 28 fractions) concurrently with chemotherapy (Capecitabine) followed by surgery after 4–8 weeks is the standard of care for locally advanced rectal adenocarcinoma in many centers worldwide.
RT is associated with certain adverse effects. The immediate adverse events such as skin erythema, diarrhea, nausea, pain, fatigue, are well documented in several trials. Longer survival and increased follow-up in this group of patients have led to the awareness of long time side effects attributable to both radiation and surgery. Common late effects of radiotherapy for rectal cancer are gastrointestinal disorders, neurological problems, anal dysfunction, urinary abnormality, pelvic or hip fractures, thromboembolic diseases and secondary cancers, etc., and are well documented in many published literature.
Sexual dysfunction is another late adverse effect of RT in rectal cancer patients, which did not gain much attention. Of the randomized trials done so far, the Dutch TME trial found increased grades of sexual dysfunction in irradiated patients as compared to surgery only patients, and the difference was more in females.
Bruheim et al., in a large retrospective cohort, found that RT for rectal cancer is associated with significantly more sexual dysfunction than surgery alone and recommended additional insight in the mechanisms leading to sexual dysfunction is needed to find measures for prevention.
Marijnen et al. in a multicenter randomized trial reported that among rectal carcinoma patients, the decline of sexual activity is more in the group receiving preoperative radiotherapy than those who had surgery only. In the case of males, both erection and ejaculation problems increased in the group receiving preoperative radiotherapy (P = 0.002). For females, both vaginal dryness and pain during intercourse were worse in the patients treated with preoperative radiotherapy when compared with the group not receiving preoperative radiotherapy (P < 0.001), leading to the deterioration of sexual function.
In the literature, it is found that many authors have recorded and reported median genitalia dose in case of radiotherapy in anal cancer [Table 3], but we could not find such reporting of external genitalia dose in rectal cancer patients who undergo preoperative radiotherapy.
|Table 3: The median (range) genitalia dose reported from a various literature in anal cancer intensity modulated radiotherapy|
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In this study, we had recorded the radiotherapy dose received by external genitalia during preoperative radiotherapy in rectal cancer patients and observed that, in case of male patients, the genitalia receive relatively more radiation dose when treated in the supine position, but in case of females such observation was not made. The external female genitalia is relatively fixed and do not move with different body positions as compared to the male external genitalia. Therefore, the DVH values obtained for female patients in both supine and prone position did not differ much. However, in this study, the external genitalia of both the gender received an average of 40%–53% of the total prescribed dose when treated with standard three-field technique, which is significantly high.
We cannot directly compare our results with the results of previous literature, as shown in [Table 3], as they have done their work only in anal cancer patients.
| Conclusion|| |
Preoperative radiotherapy for locally advanced rectal cancer patients is standard of care in most of the institutions. Retrospective studies have shown that the use of radiotherapy in this group of patients has shown to develop various sexual morbidities. We could not found any published literature till date correlating between dose received by the external genital organs and the development of various sexual morbidities. In our study, we found that the external genital organs receive an average of 40%–53% of the total prescribed dose when treated with standard three-field wedged technique. Therefore we suggest that the young sexually active patients may be treated with better conformal techniques to reduce the radiation dose received by the external genitals as low as possible.
The main limitation of our observation is that the disease characteristics of the study population are not homogeneous such as the lower extent of the disease is not taken in to account, which have a significant impact on the dose to the genitalia. Therefore, unbiased selection of cases and studies in a larger population needs to be done to re-affirm our findings.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Bray F, Ferlay J, Soerjomataram I, Siegel R, Torre L, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424.
Patil P, Saklani A, Gambhire P, Mehta S, Engineer R, De'Souza A, et al
. Colorectal cancer in India: An audit from a tertiary center in a low prevalence area. Indian J Surg Oncol 2017;8:484-90.
Vuik F, Nieuwenburg S, Bardou M, Lansdorp-Vogelaar I, Dinis-Ribeiro M, Bento M, et al
. Increasing incidence of colorectal cancer in young adults in Europe over the last 25 years. Gut 2019;68:1820-6.
Hussain N, Gahine R, Mourya J, Sudarshan V. Colorectal cancer in young adults in a tertiary care hospital in Chhattisgarh, Raipur. Indian J Cancer 2013;50:337.
] [Full text]
Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S, et al
. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): A multicentre, randomised trial. Lancet 2009;373:811-20.
Folkesson J, Birgisson H, Pahlman L, Cedermark B, Glimelius B, Gunnarsson U. Swedish rectal cancer trial: Long lasting benefits from radiotherapy on survival and local recurrence rate. J Clin Oncol 2005;23:5644-50.
van Gijn W, Marijnen CA, Nagtegaal ID, Kranenbarg EM, Putter H, Wiggers T, et al
. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol 2011;12:575-82.
Marijnen CA, van de Velde CJ, Putter H, van den Brink M, Maas CP, Martijn H, et al
. Impact of short-term preoperative radiotherapy on health-related quality of life and sexual functioning in primary rectal cancer: Report of a multicenter randomized trial. J Clin Oncol 2005;23:1847-58.
Donovan KA, Thompson LM, Hoffe SE. Sexual function in colorectal cancer survivors. Cancer Control 2010;17:44-51.
Bonnel C, Parc YR, Pocard M, Dehni N, Caplin S, Parc R, et al
. Effects of preoperative radiotherapy for primary resectable rectal adenocarcinoma on male sexual and urinary function. Dis Colon Rectum 2002;45:934-9.
Marks LB, Ten Haken RK, Martel MK. Guest editor's introduction to QUANTEC: A users guide. Int J Radiat Oncol Biol Phys 2010;76:S1-2.
Brooks C, Hansen VN, Riddell A, Harris VA, Tait DM. Proposed genitalia contouring guidelines in anal cancer intensity-modulated radiotherapy. Br J Radiol 2015;88:20150032.
Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, et al
. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N
Engl J Med 2004;351:1731-40.
Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, et al
. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: Results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol 2012;30:1926-33.
Ngan S, Burmeister B, Fisher R, Solomon M, Goldstein D, Joseph D, et al
. Randomized Trial of Short-Course Radiotherapy Versus Long-Course Chemoradiation Comparing Rates of Local Recurrence in Patients With T3 Rectal Cancer: Trans-Tasman Radiation Oncology Group Trial 01.04. Journal of Clinical Oncology. 2012;30:3827-33.
Birgisson H, Påhlman L, Gunnarsson U, Glimelius B. Late adverse effects of radiation therapy for rectal cancer-a systematic overview. Acta Oncol 2007;46:504-16.
Bruheim K, Guren MG, Dahl AA, Skovlund E, Balteskard L, Carlsen E, et al
. Sexual function in males after radiotherapy for rectal cancer. Int J Radiat Oncol Biol Phys 2010;76:1012-7.
James RD, Glynne-Jones R, Meadows HM, Cunningham D, Myint AS, Saunders MP, et al
. Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): A randomised, phase 3, open-label, 2×2 factorial trial. Lancet Oncol 2013;14:516-24.
Brooks CJ, Lee YK, Aitken K, Hansen VN, Tait DM, Hawkins MA. Organ-sparing Intensity-modulated radiotherapy for anal cancer using the ACTII schedule: A comparison of conventional and intensity-modulated radiotherapy plans. Clin Oncol (R Coll Radiol) 2013;25:155-61.
Myerson RJ, Garofalo MC, El Naqa I, Abrams RA, Apte A, Bosch WR, et al
. Elective clinical target volumes for conformal therapy in anorectal cancer: A radiation therapy oncology group consensus panel contouring atlas. Int J Radiat Oncol Biol Phys 2009;74:824-30.
Joseph KJ, Syme A, Small C, Warkentin H, Quon H, Ghosh S, et al
. A treatment planning study comparing helical tomotherapy with intensity-modulated radiotherapy for the treatment of anal cancer. Radiother Oncol 2010;94:60-6.
Vieillot S, Fenoglietto P, Lemanski C, Moscardo CL, Gourgou S, Dubois JB, et al
. IMRT for locally advanced anal cancer: Clinical experience of the Montpellier Cancer Center. Radiat Oncol 2012;7:45.
Das P, Cantor SB, Parker CL, Zampieri JB, Baschnagel A, Eng C, et al
. Long-term quality of life after radiotherapy for the treatment of anal cancer. Cancer 2010;116:822-9.
Kachnic LA, Tsai HK, Coen JJ, Blaszkowsky LS, Hartshorn K, Kwak EL, et al
. Dose-painted intensity-modulated radiation therapy for anal cancer: A multi-institutional report of acute toxicity and response to therapy. Int J Radiat Oncol Biol Phys 2012;82:153-8.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]