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  Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 55  |  Issue : 4  |  Page : 327-335
 

A comparative analysis of quality of life after postoperative intensity-modulated radiotherapy or three-dimensional conformal radiotherapy for cervical cancer


1 Department of Radiation Oncology, Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, Maharashtra, India
2 Department of Radiation Oncology, Tata Memorial Hospital, Navi Mumbai, Maharashtra, India
3 Epidemiology and Clinical Trials Unit, Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, Maharashtra, India
4 Department of Medical Oncology, Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, Maharashtra, India

Date of Web Publication28-Feb-2019

Correspondence Address:
Supriya Chopra
Department of Radiation Oncology, Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijc.IJC_453_17

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 » Abstract 


AIMS: The aim of this study is to compare the quality of life (QOL) between adjuvant three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) for cervical cancer. MATERIALS AND METHODS: QOL assessment was done at the baseline and then longitudinally after completing (chemo) radiation. All patients completed EORTC QLQ-C30 and EORTC QLQ Cx-24 modules. Independent-sample t-test was used to compare the mean scores between the two groups. Analysis of variance was used to compare differences in QOL measures over the six time points (baseline, post-RT, 3, 6, 9, and 12 months after treatment) and between treatment groups (3DCRT vs. IMRT). Linear mixed model was also performed to account for attrition. RESULTS: Overall, 64 patients (image-guided IMRT, n = 40 and 3DCRT, n = 24) completed QOL assessment. The median age and follow-up period were 48 years and 15.5 months, respectively. General QOL domains such as emotional (at 12 months, P = 0.04) and social (at 3 months, P = 0.02 and 12 months, P = 0.03) were better with IMRT. Pain (12 months, P = 0.03); fatigue (12 months, P = 0.05); nausea and vomiting (12 months, P = 0.03); insomnia (post-RT, P = 0.05 and 12 months, P = 0.03); appetite loss (post-RT and 12 months, P = 0.04); and diarrhea (6 months, P = 0.02 and 12 months, P = 0.003) scores were significantly better with IMRT. On linear mixed model analysis, there was a significant interaction between treatment cohort and assessment intervals for physical, emotional, and social functioning, appetite loss, diarrhea, lymphedema, and menopausal symptom scores were significantly better with IMRT. CONCLUSIONS: Treatment technique (IMRT vs. 3DCRT) impacts early QOL in undergoing adjuvant radiation for cervical cancer.


Keywords: Cervical cancer, intensity-modulated radiotherapy, quality of life, three-dimensional conformal radiotherapy


How to cite this article:
Mohanty SK, Chopra S, Mudaliar A, Kannan S, Mahantshetty U, Engineer R, Ghosh J, Bajpai J, Gupta S, Shrivastava S. A comparative analysis of quality of life after postoperative intensity-modulated radiotherapy or three-dimensional conformal radiotherapy for cervical cancer. Indian J Cancer 2018;55:327-35

How to cite this URL:
Mohanty SK, Chopra S, Mudaliar A, Kannan S, Mahantshetty U, Engineer R, Ghosh J, Bajpai J, Gupta S, Shrivastava S. A comparative analysis of quality of life after postoperative intensity-modulated radiotherapy or three-dimensional conformal radiotherapy for cervical cancer. Indian J Cancer [serial online] 2018 [cited 2019 May 21];55:327-35. Available from: http://www.indianjcancer.com/text.asp?2018/55/4/327/253295





 » Introduction Top


Long-term follow-up of postoperative radiotherapy in endometrial cancer (PORTEC) studies reports health-related quality of life (HRQOL) after surgery with or without pelvic external beam radiation therapy (EBRT) or vaginal brachytherapy (VB) in women with endometrial cancer (EC).[1] Complex interactions between organ damage caused by pelvic EBRT or VB and resultant functional and symptom scales determine HRQOL.[2],[3] Similar to EC, surgery, radiotherapy, and chemotherapy are also effective treatment options for cervical cancer, and these are used in combination for improving survival in women with early cervical cancer.[4],[5],[6],[7] At present, the use of EBRT and VB and/or chemotherapy constitutes the standard of care in patients with intermediate- or high-risk cervical cancer.[5],[6],[8] However, the use of these aforementioned treatment regimens increases the chance of late treatment effects, especially gastrointestinal (GI).[9] HRQOL within PORTEC studies reports QOL following EBRT or VB alone. It is likely that the combination of pelvic three-dimensional (3D) EBRT and VB along with concurrent chemotherapy may lead to greater organ damage and hence inferior QOL. Unlike EC, the impact of adjuvant EBRT and VB on QOL has not been systematically investigated in patients with cervical cancer. In recent years, the use of newer radiation techniques such as image-guided intensity-modulated radiotherapy (IMRT) has led to reduced acute and late toxicity,[10],[11],[12],[13] which may decrease patient-reported symptoms and improve long-term QOL. The present comparative analysis was designed to investigate if the use of newer techniques such as IMRT is associated with improved QOL compared to 3DEBRT.


 » Subjects and Methods Top


Patients undergoing postoperative adjuvant or salvage pelvic radiation (with or without chemotherapy) for cervical cancer within the context of ongoing institutional review board approved trials wherein QOL assessment was included in the basic study design as a secondary endpoint were eligible (clinical trials.gov NCT 01279135, 01391065). All eligible patients were required to be disease free and should have completed at least 1-year follow-up period with regular assessments of QOL. The treatment included EBRT with or without concurrent cisplatin 40 mg/m 2. While in NCT 01391065, all patients received 3D conformal radiotherapy (3DCRT) (4-field box); in another trial (NCT 01279135), the treatment allocation was IMRT as per randomization [Figure 1].[14] All patients underwent CT-based RT planning. Targets and organs at risk were delineated. Internal target volume was delineated using empty and full bladder scans. Whenever two scans were not feasible, a population-based internal target margin was used.[15],[16] Conformal planning was used for 3DCRT cohort to minimize radiation exposure to organs at risk. During IMRT planning, dose constraints were used to restrict the volume of small bowel receiving 15 and 40 Gy (V15/V40 SB) to <190 cc and <100 cc, respectively. No prospective constraints were applied to rectum, bladder, or bone marrow. A total of 50 Gy/25 fractions were prescribed to primary and nodal PTV and were delivered over 5 weeks with or without concurrent cisplatin. All patients received CT-based intra-VB.
Figure 1: The consort diagram showing arms three-dimensional conformal radiotherapy and intensity-modulated radiotherapy

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Quality of life assessments

QOL assessment was done at the baseline (pre-(chemo) radiotherapy) and then longitudinally after completing planned (chemo) radiation every 3 months for 2 years and every 6 months thereafter. All patients completed the European Organization for Research and Treatment of Cancer core questionnaire (EORTC QLQ-C30) and EORTC cervix-specific module (EORTC QLQ Cx-24) assisted by trained nurse interviewer. In addition, sociodemographic questions such as age, educational status, occupation, income, and marital status were asked to all of the participants.

The EORTC QLQ-C30 questionnaire comprises five multi-item functional scales: physical, role, social, emotional, and cognitive functioning; three symptom scales (pain, fatigue, and nausea and vomiting); a global QOL scale, and six single items. All scales and single questions were scored on a categorical scale and numerically transformed to a score of 1–100. The EORTC QLQ Cx-24 is the module used specifically for the cervical cancer patients.[17] It comprises 24 questions consisting of four functional scales assessing body image, sexual activity, sexual enjoyment, and sexual and vaginal functioning and five symptom scales assessing sexual experience, peripheral neuropathy, menopausal status, lymphedema, and sexual worry. All scores on these questionnaires were linearly transformed such that all scales ranged from 0 to 100 according to the EORTC scoring manual recommendations. The missing data were processed according to the EORTC manual guidelines. Higher functional or global QOL scale represents a high healthy level of functioning, whereas a high score for a symptom scale represents the presence of a symptom or problems. All the core and specific module questionnaires were delivered to the patients in their vernacular language such as Hindi and Marathi wherever applicable.

Ethics

We declare that all procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional review board) and the Helsinki Declaration

Statistical analysis

Any patient who filled the QOL questionnaire at least at two time points at follow-up was included in the present analysis. The baseline characteristics of the two groups were compared using Chi-square test. As per EORTC QLQ scoring manual guidelines, mean scores of the QOL scales were calculated. Demographic and clinical data were calculated using descriptive statistics. An independent sample t-test was used to compare the mean scores between the two groups at each time point. Repeated-measures analysis of variance was used to compared differences in QOL measures over the six time points (baseline, then immediate post-RT, 3, 6, 9, and 12 months after treatment) and between treatment groups (3DCRT vs. IMRT, average of the six time points). A univariate approach was adopted to test within-subject effects (i.e., differences over the four time points); the Huynh-Feldt Epsilon correction factor was used to adjust the univariate test degrees of freedom if the assumption of sphericity was violated (determined by Mauchly's test of sphericity). Differences in scores between the groups were also compared at individual time points. Because attrition is always a concern in longitudinal QOL data, linear mixed model was also used for imputing missing values and enhancing power in a post hoc exploratory analysis. The linear mixed model includes the main effect of the treatment group (difference in overall means between 3DCRT and IMRT) and an interaction effect of the treatment group with time (difference in slope between 3DCRT and IMRT). All tests were two-tailed, and differences were considered statistically significant at the 0.05 level. For better interpretation of results, clinical significance of the comparison of scales between the two arms was also analyzed. For the EORTC questionnaires, changes in time of 10 points or more are considered clinically relevant. Results were considered significant only if they were both statistically significant (P ≤ 05) as well as clinically meaningful (≥10-point difference in mean scores). All data were analyzed using statistical software SPSS version 20, IBM, Armonk, NY, United States of America, GraphPad Instat version 3.1, and Microsoft Excel 2007.


 » Results Top


Seventy-one patients were included in this study. Out of the total cohort, six patients (1 in 3DCRT arm and 5 in IMRT arm) were excluded as they had not completed 1-year post-RT. One patient was purposefully excluded due to the presence of vaginal disease at follow-up. Overall, 55/64 (85.9%) patients completed QOL questionnaire at all six time points (baseline, post-RT, 3, 6, 9, and 12 months). The median age and median follow-up period were 48 years (35–62 years) and 15.5 months (6–27 months), respectively. Overall, 24 (37.5%) patients underwent simple hysterectomy and 40 (62.5%) underwent Type III hysterectomy. Baseline demographics and characteristics of the study cohort have been described in [Table 1]. Of the patients, 40 (62.5%) received tomotherapy-based IMRT and 24 (37.5%) received 3D conformal radiation. Overall, 53 of the 64 patients (82.8%) received concurrent weekly cisplatin. All patients included in this study received VB.
Table 1: Baseline patient and disease characteristics of study cohort (n=64)

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There was nonsignificant difference in the patient and disease characteristics between the two groups at the baseline except treatment technique (3DCRT or IMRT). Baseline scores for global QOL, diarrhea, sexual activity, and sexual enjoyment scale were well balanced between the two arms ensuring comparability [Table 1].

Quality of life outcomes comparison between three-dimensional conformal radiotherapy and intensity-modulated radiotherapy

Functional scales

The mean scores of QOL domains at different time points in 3DCRT versus IMRT arms are shown in [Table 2]. Global QOL was not significantly affected by radiotherapy technique except at treatment completion with higher score in IMRT (P = 0.03) compared to 3DCRT. However, the global score was increased at 12 months compared to the baseline, though not statistically significant. Treatment with IMRT had a positive effect on some general as well as cervix-specific QOL domains. General QOL domains such as emotional functioning (12 months, P = 0.04) and social functioning (3 months, P = 0.02 and 12 months, P = 0.03) were better with IMRT.
Table 2: Mean scores of quality of life domains in patients treated with three-dimensional conformal radiotherapy versus intensity-modulated radiotherapy at different time points

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Symptom scales

Among the symptom scales, pain score (12 months, P = 0.03); fatigue score (12 months, P = 0.05); nausea and vomiting score (12 months, P = 0.03); insomnia (Post-RT, P = 0.05 and 12 months, P = 0.03); appetite loss (post-RT and 12 months, P = 0.04); and diarrhea (6 months, P = 0.02 and 12 months, P = 0.003) were significantly better with IMRT compared to 3DCRT. Lymphedema and menopausal symptoms were generally better with IMRT compared to 3DCRT and statistically significant at least at one time point. None of the QOL domains was worse with IMRT in comparison with 3DCRT at any time point, which was statistically significant except for dyspnea score and peripheral neuropathy. [Figure 2] compares the absolute change in mean scores of QOL domains at different time points between 3DCRT and IMRT. [Figure 3] depicts the proportion of patients with moderate-to-severe GI and genitourinary symptom scores.
Figure 2: Comparison of absolute change in mean scores for quality of life domain (a) physical functioning, (b) emotional functioning, (c) social functioning, (d) appetite loss, (e) diarrhea, (f) lymphedema between three-dimensional conformal radiotherapy and intensity-modulated radiotherapy

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Figure 3 (a-n): Figure depicts proportion of patients with mild, moderate, and severe gastrointestinal and genitourinary symptoms in three-dimensional conformal radiotherapy and image-guided intensity-modulated radiotherapy cohort at 12 months

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Time trends

Overall QOL patterns were analyzed for the 55 patients (85.9%) who completed QOL questionnaires at all six time intervals. There were statistically significant changes in several scales over these periods [Table 3] and [Table 4]. Overall, IMRT cohort had higher functional scale scores and lower symptom item scores indicating a better QOL.
Table 3: EORTC QLQ-Cx24 data at baseline and postradiotherapy, 3, 6, 9 and 12 months' postradiotherapy (three-dimensional conformal radiotherapy, n=22; intensity-modulated radiotherapy, n=33) by repeated measures analysis of variance

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Table 4: Exploratory linear mixed model analysis showing quality of life measures that showed significant interaction between treatment arms (three-dimensional conformal radiotherapy versus intensity-modulated radiotherapy) and time. *P is for treatment arm as an overall effect over all the assessment intervals, P is for difference in scores between the groups at all time intervals, P is for interaction of category and assessment time interval

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Most QOL domains were associated with temporary deterioration after RT followed by gradual recovery over time. Among the symptom and item scales, pain, fatigue, nausea and vomiting, dyspnea, appetite loss, diarrhea, financial problems, sexual experience, and peripheral neuropathy showed significant change over time [Table 3] and [Table 4]. Among functional scores, all domains except sexual enjoyment and sexual and vaginal function scores showed significant change over time. Global QOL score was expectedly worst at post-RT period; however, this recovered rapidly by 3 months and then remained stable over time.

QOL data from patients who completed at least one follow-up questionnaire were also used to study time trends. [Figure 4]a and [Figure 4]b shows the pattern of recovery for both QLQ C30 and Cx-24 of QOL over time. Absolute change in QOL scores is plotted over time wherein negative scores show deterioration in QOL parameters whereas positive scores indicate recovery. Global QOL, physical, emotional, social, cognitive functioning, pain, fatigue, insomnia, and constipation recovered at 3–6 months, whereas nausea and vomiting and loss of appetite recovered gradually and slowly beyond 6 months. Only role functioning and financial instability showed positive absolute change beyond posttreatment.
Figure 4: (a) Patterns of recovery of different QOL domains in patients with cervical cancers treated with high-precision conformal techniques (3D-CRT or IG-IMRT), (b) Patterns of recovery of different QOL domains in patients with cervical cancers treated with high-precision conformal techniques (3D-CRT or IG-IMRT)

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Sexual quality of life

In the 3DCRT arm, 15.8% of the patients were sexually active at the baseline, whereas in IMRT arm, 9.4% of patients were sexually active. Similarly, the corresponding proportions (3DCRT vs. IMRT) at post-RT, 6 months, and 12 months were 0% versus 0%, 21.7% versus 8.1%, and 17.4% versus 11.4% respectively. Among the cervix-specific domains, only body image, peripheral neuropathy, and menopausal symptoms recovered in a positive manner posttreatment; however, there was deterioration in sexual and vaginal functioning at 12 months when compared to the baseline.

Linear mixed model

There was a significant change in almost all functional, symptom, and item scores at all time periods except lymphedema and sexual worry [Table 5]. There was a significant interaction between treatment arm (3DCRT versus IMRT), and assessment intervals for seven QOL subscale scores, namely, physical functioning (81.4 vs. 86.2), emotional functioning (67.6 vs. 75.6), social functioning (71.5 vs. 78.8), appetite loss (28 vs. 17.2), diarrhea (15.7 vs. 9.15), lymphedema (10.4 vs. 4.2), and menopausal symptom (11.7 vs. 7.7) scores were significantly better with IMRT [Table 5]. There was a significant interaction between category and time intervals for social function, sleep disturbances, and menopausal symptoms where IMRT was better than 3DCRT.
Table 5: EORTC QLQ-C30 data at baseline and postradiotherapy, 3, 6, 9, and 12 months' postradiotherapy (three-dimensional conformal radiotherapy, n=22; intensity-modulated radiotherapy, n=33) by repeated measures analysis of variance

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 » Discussion Top


The impact of adjuvant pelvic EBRT or VB is best captured by long-term HRQOL from PORTEC studies, which has upto 10 years of follow-up in women with EC.[1] However, only few studies describe intermediate and long-term QOL outcomes in cervical cancer among patients undergoing surgery or radiation.[1],[18] The present comparative analysis investigated differences if any between 3DCRT and IMRT after postoperative pelvic radiation in patients with cervical cancer using EORTC QLQ-C30 and Cx-24. Although different subscales have been used to investigate site-specific organ dysfunction, it is noteworthy that the mean scores within PORTEC EBRT arm at 12 and 84 months are almost similar to those observed in the present postoperative cervical cancer 3DCRT cohort at 12 months. Lack of clinically significant difference in mean scores between the 3DCRT cohort and PORTEC EBRT arm suggests cross-cultural applicability of our study findings.

In the present study before performing comparative analysis, we ensured that the baseline parameters were well balanced. Although insomnia was greater in IMRT cohort, the difference in baseline QOL scores in both cohorts was statistically insignificant. Over 12 months of follow-up, we observed a significant time trend in the recovery of most functional, symptom, and sexual function scales that was independent of treatment technique for most functional and symptom domains. While an interim analysis of an ongoing randomized trial of postoperative IMRT and 3DCRT demonstrated almost 14% reduction in grade ≥II toxicity at 18 months, we observed that patients begin to report these differences as early as 9 months.[13] In the present study, the use of IMRT was associated with improved appetite and reduced incidence of diarrhea and lymphedema. In an initial validation study of Cx-24, symptom experience scale of Cx-24 correlated with functional scales.[17] Therefore, it is likely that reduction on symptom scales would have translated into improvement in functional scales within the IMRT cohort. While there was no statistically significant difference in the type of hysterectomy between 3DCRT and IMRT, IMRT cohort fared better on menopausal symptoms, the cause of which could not be ascertained.

Abayomi et al. reported that the diagnosis of the cervix (rather than EC) is an independent predictor for higher GI symptoms; however, our mean follow-up scores in cervical cancer patients are no different than that of EC patients.[14] This could be attributed to the inclusion of early-stage patients within our cohort. It is also noteworthy that, while physician reported GI toxicity scores continue to increase up to 3 years,[13],[19] patient-reported symptom scores stabilize at approximately 12 months. The results of PORTEC studies demonstrate that GI symptom scores along with most EORTC QLQ-C30 return to normal by 1 year and remain essentially stable. This could possibly be related to “response shift” where patients learn to cope with symptoms, and therefore, adjust the internal values and standards.[19],[20]

In the sexual subscale of Cx-24, the two single items on sexual worry and sexual activity were intended for completion by all patients. Even during the initial Cx-24 validation studies in 2006, sexual items had more than 60% patients who were not sexually active.[17] In the present cohort, overall, 67% of the patients responded to the single items and 25.2% were sexually active. We did not observe any difference in sexual QOL between two cohorts. We could not determine any reason for difference in menopausal symptoms in the two cohorts.

Caveats and limitations

Although this is the first comparative study of QOL outcomes for postoperative 3DCRT or IMRT, the data need to be interpreted with caution as the study relies on comparative analysis methodology ensuring balance in both arms with regard to the baseline features. It is also noteworthy that, at the baseline, IMRT cohort had statistically nonsignificant higher mean diarrhea score. This is unlikely to have affected the final analysis as at follow-up, IMRT cohort diarrhea scores were significantly lesser than the 3DCRT cohort. Although the study cohort was not very large, the strength of this study is the comprehensive longitudinal evaluation of a uniform cohort of patients undergoing postoperative radiation.


 » Conclusions Top


There is a significant reduction in QOL scores after pelvic irradiation that gradually but definitely improves over time. The results of the present comparative analysis demonstrate that the use of adjuvant IMRT may be associated with improved QOL. Although our study is limited by follow-up duration, IMRT may possibly be associated with improved long-term QOL scores. The magnitude of impairment for most QOL domains is lesser and the use of IMRT results in clinically meaningful and statistically better QOL scores (for some domains and symptom subscales at several time points) compared to 3DCRT with comparable disease outcomes that could support its widespread adoption in routine clinical practice.

Acknowledgment

We would like to thank Disease Management Group, Gynaecological Oncology, Tata Memorial Hospital, Mumbai.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

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de Boer SM, Nout RA, Jürgenliemk-Schulz IM, Jobsen JJ, Lutgens LC, van der Steen-Banasik EM, et al. Long-term impact of endometrial cancer diagnosis and treatment on health-related quality of life and cancer survivorship: Results from the randomized PORTEC-2 trial. Int J Radiat Oncol Biol Phys 2015;93:797-809.  Back to cited text no. 1
    
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Rotman M, Sedlis A, Piedmonte MR, Bundy B, Lentz SS, Muderspach LI, et al. A phase III randomized trial of postoperative pelvic irradiation in stage IB cervical carcinoma with poor prognostic features: Follow-up of a gynecologic oncology group study. Int J Radiat Oncol Biol Phys 2006;65:169-76.  Back to cited text no. 5
    
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Sedlis A, Bundy BN, Rotman MZ, Lentz SS, Muderspach LI, Zaino RJ, et al. A randomized trial of pelvic radiation therapy versus no further therapy in selected patients with stage IB carcinoma of the cervix after radical hysterectomy and pelvic lymphadenectomy: A Gynecologic oncology group study. Gynecol Oncol 1999;73:177-83.  Back to cited text no. 6
    
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Klopp AH, Moughan J, Portelance L, Miller BE, Salehpour MR, Hildebrandt E, et al. Hematologic toxicity in RTOG 0418: A phase 2 study of postoperative IMRT for gynecologic cancer. Int J Radiat Oncol Biol Phys 2013;86:83-90.  Back to cited text no. 12
    
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Chopra SR, Mahantshetty UM, Dora T, Kannan S, Phurailatpam R, Paul SN, et al. Phase III RCT of postoperative adjuvant conventional radiation (3DCRT) versus igimrt for reducing late bowel toxicity in cervical cancer (PARCER)(NCT01279135/CTRI2012/120349): Results of interim analyses. Int J Radiat Oncol Biol Phys 2015;93:S4.  Back to cited text no. 13
    
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Chopra S, Engineer R, Mahantshetty U, Misra S, Phurailatpam R, Paul SN, et al. Protocol for a phase III randomised trial of image-guided intensity modulated radiotherapy (IG-IMRT) and conventional radiotherapy for late small bowel toxicity reduction after postoperative adjuvant radiation in Ca cervix. BMJ Open 2012;2. pii: e001896.  Back to cited text no. 14
    
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Nout RA, Putter H, Jürgenliemk-Schulz IM, Jobsen JJ, Lutgens LC, van der Steen-Banasik EM, et al. Quality of life after pelvic radiotherapy or vaginal brachytherapy for endometrial cancer:First results of the randomized PORTEC-2 trial. J Clin Oncol 2009;27:3547-56.  Back to cited text no. 18
    
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Abayomi J, Kirwan J, Hackett A. The prevalence of chronic radiation enteritis following radiotherapy for cervical or endometrial cancer and its impact on quality of life. Eur J Oncol Nurs 2009;13:262-7.  Back to cited text no. 19
    
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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