Feasibility of dose escalation using intensity-modulated radiotherapy in posthysterectomy cervical carcinoma

doi:10.1016/j.ijrobp.2004.07.721

International Journal of Radiation OncologyBiologyPhysics

Volume 61, Issue 4, 15 March 2005, Pages 1062-1070

Presented in part at the 44th Annual Meeting of the American Association of Physicists in Medicine, Montreal, ON, Canada, 2001.

https://doi.org/10.1016/j.ijrobp.2004.07.721 Get rights and content

Purpose

To evaluate retrospectively the utility of intensity-modulated radiotherapy (IMRT) in reducing the volume of normal tissues receiving radiation at varying dose levels when the female pelvis after hysterectomy is treated to doses of 50.4 Gy and 54 Gy.

Methods and materials

Computed tomography scans from 10 patients who had previously undergone conventional postoperative RT were selected. The clinical tumor volume (vaginal apex and iliac nodes) and organs at risk were contoured. Margins were added to generate the planning tumor volume. The Pinnacle and Corvus planning systems were used to develop conventional and IMRT plans, respectively. Conventional four-field plans were prescribed to deliver 45 Gy (4F_{45 Gy}) or 50.4 Gy; eight-field IMRT plans were prescribed to deliver 50.4 Gy (IMRT_{50.4 Gy}) or 54 Gy (IMRT_{54 Gy}) to the planning tumor volume. All plans were normalized so that ≥97% of the planning tumor volume received the prescribed dose. Student's t test was used to compare the volumes of organs at risk receiving the same doses with different plans.

Results

The mean volume of bowel receiving ≥45 Gy was lower with the IMRT_{50.4 Gy} (33% lower) and IMRT_{54 Gy} (18% lower) plans than with the 4F_{45 Gy} plan. The mean volume of rectum receiving ≥45 Gy or ≥50 Gy was also significantly reduced with the IMRT plans despite an escalation of the prescribed dose from 45 Gy with the conventional plans to 54 Gy with IMRT. The mean volume of bladder treated to 45 Gy was the same or slightly lower with the IMRT_{50.4 Gy} and IMRT_{54 Gy} plans compared with the 4F_{45 Gy} plan. Compared with the 4F_{45 Gy} plan, the IMRT_{50.4 Gy} plan resulted in a smaller volume of bowel receiving 35–45 Gy and a larger volume of bowel receiving 50–55 Gy. Compared with the 4F_{45 Gy} plan, the IMRT_{54 Gy} plan resulted in smaller volumes of bowel receiving 45–50 Gy; however, small volumes of bowel received 55–60 Gy with the IMRT plan.

Conclusion

Intensity-modulated RT may permit an increase in the radiation dose that can safely be delivered to the central pelvis and pelvic lymph nodes after hysterectomy. However, dose–volume calculations using individual CT scans do not account for internal organ motion. Detailed data concerning the relationships among radiation dose, treatment volume, and treatment effects are lacking, and prospective studies of pelvic IMRT are needed to determine the safety and efficacy of this treatment.

Introduction

Radiotherapy (RT) is used in the treatment of patients presenting with cervical carcinoma who have previously undergone hysterectomy. Treatment involves irradiation of the whole pelvis, including the vaginal apex and pelvic lymph nodes. RT is usually delivered via conventional techniques with either a two-field (AP–PA) or four-field (AP–PA and two lateral beams) approach. In addition to RT, the use of concurrent chemotherapy for this cohort of patients is now commonly accepted as part of the treatment regimen (1).

Irradiation of the pelvic lymph nodes requires inclusion of a considerable volume of bowel in the treatment fields, causing significant acute and chronic side effects (2, 3). Hysterectomy causes the bowel to herniate into the trough between the iliac nodes and superior to the vaginal apex. This increases the volume of bowel irradiated in posthysterectomy patients compared with patients with an intact cervix. Randomized trials have shown that patients treated with postoperative RT have more side effects than patients undergoing surgery alone (4, 5).

Various attempts have been made to reduce the volume of bowel in the field during pelvic irradiation, including the use of belly boards and other physical devices (6, 7, 8). Recently, the utility of intensity-modulated RT (IMRT) in bowel dose reduction has been investigated. Several studies, including our own, have shown an improvement in bowel, rectum, and bladder dose distributions with IMRT compared with conventional RT (either two-field or four-field) in gynecologic malignancies for doses of ≤45 Gy in 25 fractions (9, 10, 11, 12).

Studies have shown that pelvic recurrences still develop despite RT after hysterectomy (1, 4). Data from studies in patients with high-risk uterine or cervical cancer (1, 4, 5, 13) and from studies in patients with head-and-neck cancer (14, 15) have shown that doses >45–50 Gy may be needed to control subclinical squamous carcinoma in the postoperative setting. However, bowel side effects have prevented escalation to the female pelvis in postoperative cervical carcinoma cases. IMRT makes it possible to deliver highly conformal doses to the tumor while sparing normal tissues. On the basis of the initial success of previous investigators and ourselves in delivering conventional doses via IMRT (9, 10, 11, 12), we investigated the feasibility of escalating the dose to the pelvis to 50.4 Gy in 28 fractions and 54 Gy in 30 fractions using IMRT and compared the bowel, rectum, and bladder dose–volume relationships between escalated doses delivered using IMRT and escalated and standard doses delivered using conventional techniques.

Section snippets

Methods and materials

Ten patients who had previously undergone treatment simulation with CT (PQ 5000, Marconi Medical Systems, Cleveland, OH) and had undergone posthysterectomy conventional RT (two-field or four-field) were selected for this study. CT scans were obtained from L3-L4 to below the introitus. The CT image data were derived from patients who had been treated for either endometrial or cervical cancer. However, we contoured the volumes on all the CT images that would have been appropriate for routine

Results

Figure 2 shows axial CT images of a representative patient with overlaid isodose lines (54, 50.4, 45, and 35 Gy) obtained from the 4F_{45 Gy} and 4F_{50.4 Gy} (Fig. 2a,b) and IMRT_{50.4 Gy} and IMRT_{54 Gy} (Fig. 2c,d) plans. Figure 3 shows sagittal CT images from the same patient with superimposed isodose lines (54, 50.4, 45, and 35 Gy) for the plans in Fig. 2. A comparison between the conventional and IMRT plans revealed that, in general, the isodose lines conformed more tightly around the PTV in the

Discussion

The feasibility of delivering standard radiation doses to the female pelvis via IMRT has previously been demonstrated by us, as well as other groups (9, 10, 11, 12), making it possible to explore the delivery of escalated doses using IMRT. In conventional treatment plans, most of the intrapelvic bowel is included in the field. IMRT can significantly reduce the volume of bowel receiving relatively high radiation doses. The present study suggests that patients who require >45 Gy to achieve a high

Conclusion

The results of our study have demonstrated the theoretical feasibility of escalating the dose up to 54 Gy using IMRT for posthysterectomy pelvic irradiation and demonstrated improved sparing of organs at risk with IMRT plans compared with similar doses delivered with conventional techniques. The results of this study do not establish that these doses can routinely be administered using IMRT. The lack of detailed dose–volume effect data makes it difficult to predict accurately the risk of acute

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Comparison of clinical outcomes and toxicity in endometrial cancer patients treated with adjuvant intensity-modulated radiation therapy or conventional radiotherapy
2014, Journal of the Formosan Medical Association
Citation Excerpt :
This increases the risk of acute and late gastrointestinal (GI) and genitourinary (GU) toxicity. Several studies4–8 showed that intensity-modulated radiotherapy (IMRT) reduces the irradiated volume of normal tissue in gynecologic malignancies and this tends to lessen the acute and late GI and GU toxicity. To the best of our knowledge, only two studies9,10 have compared WPRT and IMRT and the results showed a potential dosimetric advantage of IMRT over WPRT in postoperative endometrial cancer patients.
To evaluate the treatment outcomes and toxicity in endometrial cancer patients treated with hysterectomy and adjuvant intensity-modulated radiation therapy (IMRT) or conventional radiotherapy (CRT).
There were 101 patients with stage IA-IIIC2 endometrial carcinoma treated with hysterectomy and adjuvant radiotherapy. In total, 36 patients received adjuvant CRT and 65 were treated with adjuvant IMRT. The endpoints were overall survival, local failure-free survival, and disease-free survival. Patients were assessed for acute toxicity weekly according to the Common Terminology Criteria for Adverse Events version 3.0. Late toxicity was evaluated according to the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Schema.
The 5-year overall survival, local failure-free survival, and disease-free survival for the CRT group and the IMRT group were 82.9% versus 93.5% (p = 0.26), 93.7% versus 89.3% (p = 0.68), and 88.0% versus 82.8% (p = 0.83), respectively. Four (11.1%) patients had Grade 3 or greater acute gastrointestinal (GI) toxicity and three (8.3%) patients had Grade 3 or greater acute genitourinary (GU) toxicity in the CRT group, whereas four (6.2%) patients had Grade 3 or greater acute GI toxicity in the IMRT group and no patient had severe GU toxicity. There was one (2.8%) patient who had Grade 3 or greater late GI toxicity and one (2.8%) patient had Grade 3 or greater late GU toxicity in the CRT group, whereas no patient had severe GI or GU toxicity in the IMRT group.
Adjuvant IMRT for endometrial cancer patients had comparable clinical outcomes with CRT and had less acute and late toxicity.
Applicator-guided volumetric-modulated arc therapy for low-risk endometrial cancer
2013, Medical Dosimetry
Citation Excerpt :
From this point of view, the search for new treatment modalities, such as intensity-modulated radiotherapy (IMRT) or stereotactic radiotherapy have been explored extensively.9–14 Some studies have been performed with the aim to compare IMRT with standard conventional radiotherapy (3D-CRT) for pelvic treatments, finding a significant reduction in OARs irradiation with IMRT planning and suggesting a potential decrease of both acute and late treatment-related toxicities.15–20 Regarding the irradiation of the vaginal vault alone, the IMRT technique was proposed as an alternative to high-dose-rate brachytherapy (HDR-BRT) in the postoperative radiotherapy of endometrial carcinoma,21 showing that IMRT plans had comparable planning target volume (PTV) coverage but lower inhomogeneity and lower rectal/bladder doses than HDR therapy, thus prompting further clinical investigations.
The aim of this study was to report the feasibility of volumetric-modulated arc therapy (VMAT) in the postoperative irradiation of the vaginal vault. Moreover, the VMAT technique was compared with 3D conformal radiotherapy (3D-CRT) and fixed-field intensity-modulated radiotherapy (IMRT), in terms of target coverage and organs at risk sparing. The number of monitor units and the delivery time were analyzed to score the treatment efficiency. All plans were verified in a dedicated solid water phantom using a 2D array of ionization chambers. Twelve patients with endometrial carcinoma who underwent radical hystero-adenexectomy and fixed-field IMRT treatments were retrospectively included in this analysis; for each patient, plans were compared in terms of dose-volume histograms, homogeneity index, and conformity indexes. All techniques met the prescription goal for planning target volume coverage, with VMAT showing the highest level of conformity at all dose levels. VMAT resulted in significant reduction of rectal and bladder volumes irradiated at all dose levels compared with 3D-CRT. No significant differences were found with respect to IMRT. Moreover, a significant improvement of the dose conformity was reached by VMAT technique not only at the 95% dose level (0.74 vs. 0.67 and 0.62) but also at 50% and 75% levels of dose prescription. In addition, VMAT plans showed a significant reduction of monitor units by nearly 28% with respect to IMRT, and reduced treatment time from 11 to <3 minutes for a single 6-Gy fraction. In conclusion, VMAT plans can be planned and carried out with high quality and efficiency for the irradiation of vaginal vault alone, providing similar or better sparing of organs at risk to fixed-field IMRT and resulting in the most efficient treatment option. VMAT is currently our standard approach for radiotherapy of low-risk endometrial cancer.
Dose Escalation by Intensity-modulated Radiotherapy Boost after Whole Pelvic Radiotherapy in Postoperative Patients of Carcinoma Cervix with Residual Disease
2013, Clinical Oncology
Citation Excerpt :
No reports documenting the tumour dose–volume relationship for the group of patients considered in this study were found in the literature. D'Souza et al. [12] conducted a feasibility study to evaluate the utility of IMRT plans in postoperative cases of carcinoma cervix that had undergone conventional postoperative radiotherapy. They studied conventional four-field IMRT plans to deliver 45 or 50.4 Gy and eight-field IMRT plans to deliver 50.4 or 54 Gy to the PTV and concluded on the basis of dosimetric analysis that IMRT may permit an increase in radiation dose that can safely be delivered to the central pelvis and pelvic lymph nodes after hysterectomy.
External beam radiotherapy followed by brachytherapy is the standard treatment for patients with carcinoma cervix. However, for patients who come from peripheral hospitals after incomplete surgery, whole pelvic radiotherapy (WPRT) followed by boost with either vaginal vault brachytherapy if suitable or further external beam radiotherapy is recommended. This study was conducted to evaluate if it was possible to give a higher tumour dose using intensity-modulated radiotherapy for that group of patients who were not suitable for high dose rate vaginal vault brachytherapy because of gross disease after WPRT.
A prospective study was carried out from 2005 to 2010 in which 25 postoperative patients of cervical carcinoma with gross residual disease after WPRT of 46 Gy/23 fractions/4.5 weeks were included. Nine patients were treated with 20 Gy to the planning target volume and 30 Gy to the clinical target volume in 10 fractions; 16 patients were treated with 30 Gy to the planning target volume and 35 Gy to the clinical target volume in 15 fractions. The end points of this study were local control, survival and treatment-related toxicity.
The median follow-up was 38 months. The 3 year local control, progression-free survival and overall survival rates were 76, 74 and 67%, respectively. Late grade 2 rectal toxicity was seen in 11 patients. Grade 2 bladder toxicity occurred in two patients and grade 3 bowel toxicity in two patients. No other grade 3 or higher toxicity was seen.
Inadequate and inappropriate surgery in invasive cervical cancer with resulting gross residual disease is common in India. It is possible to escalate the tumour dose by intensity-modulated radiotherapy boost after WPRT in postoperative cervical carcinoma patients with gross residual disease with low incidence of severe toxicity and excellent local control.
Dosimetric comparison between the intensity modulated radiotherapy with fixed field and Rapid Arc of cervix cancer
2012, Cancer/Radiotherapie
La chimioradiothérapie complétée par une curiethérapie est le traitement standard des cancers du col utérin localement évolués. La radiothérapie est responsable de toxicité digestive et hématologique, majorée par la chimiothérapie. L’utilisation de la radiothérapie conformationnelle avec modulation d’intensité (RCMI) par des faisceaux statiques permet une diminution de cette toxicité. La technique de RCMI RapidArc^® pourrait améliorer l’épargne des organes à risque et l’homogénéité du volume-cible prévisionnel, tout en diminuant le temps de traitement.
L’objectif de l’étude est la comparaison des plans de traitement de 20 patientes, simulés en RCMI par faisceaux fixes et RapidArc^®. Les volumes cibles étaient le volume-cible anatomoclinique (volume tumoral macroscopique, utérus, tiers supérieur du vagin, aires ganglionnaires obturatrices, iliaques et présacrées), et le volume-cible prévisionnel (volume-cible anatomoclinique +1 cm). Les organes à risque délinéés étaient le rectum, la vessie, l’intestin et la moelle osseuse. La dose prescrite était de 45 Gy en 25 fractions. La RCMI classique a été délivrée par cinq faisceaux fixes et la RCMI RapidArc^® par deux arcs. Les comparaisons ont été effectuées par le test non paramétrique de Wilcoxon.
La couverture moyenne du volume-cible prévisionnel était supérieure avec la RCMI RapidArc^® (p = 0,01). Elle permettait une meilleure épargne intestinale (p = 0,01) et la RCMI par faisceaux fixes, une meilleure épargne vésicale (p = 0,01) et rectale (p = 0,05). Le volume total recevant 20 Gy était moins grand avec la RCMI RapidArc^® (p < 0,001). Le RCMI RapidArc^® permettait de diminuer le temps de traitement (trois contre 12 minutes avec les faisceaux fixes) et le nombre d’unités moniteur (UM) (376,5 contre 962,2 en moyenne, p = 0,0001).
La technique de RCMI RapidArc^® semble apporter des résultats dosimétriques supérieurs à ceux de la RCMI par faisceaux fixes, avec moins d’UM et temps de traitement plus court.
Concurrent radiochemotherapy is the standard treatment for locally advanced cervical cancer. This treatment is responsible for bowel and hematologic toxicities. The use of intensity-modulated radiotherapy (IMRT), in static beams, allows a decrease of this toxicity. The technique of RapidArc^® IMRT could lower the dose delivered to the organs at risk and improve the homogeneity of the planning target volume coverage, while decreasing the processing time.
For 20 patients, treatment plans performed with IMRT and RapidArc^® were compared. The target volumes were: the clinical target volume (gross tumour volume, uterus, upper third of the vagina, the hypogastric, iliac and presacral nodal regions), and the planning target volume (clinical target volume + 1 cm). The delineated organs at risk were: rectum, bladder, bowel and bone marrow. The dose was 45 Gy in 25 fractions. IMRT were delivered with five beams and RapidArc^® with two arcs. The comparisons were made by the non-parametric test of Wilcoxon.
Medium coverage of the planning target volume was better with RapidArc^® (P = 0.01). It was also better regarding the sparing of bowel (P = 0.01) and IMRT was better regarding the sparing of bladder (P = 0.01) and rectum (P = 0.05). The total volume receiving 20 Gy was less important with RapidArc^® (P < 0.001). RapidArc^® allowed to decrease the treatment time (3 versus 12 minutes with IMRT) and the number of monitor units (MU) (376.5 versus 962.2, on average, P = 0.0001).
The technique of RapidArc^® seems to obtain better dosimetric results compared to RCMI, with fewer MU, and a significant decrease in treatment time.
Assessment of organ motion in postoperative endometrial and cervical cancer patients treated with intensity-modulated radiation therapy
2011, International Journal of Radiation Oncology Biology Physics
Citation Excerpt :
This study was undertaken to attempt to better define the treatment margins around target volumes required that account for vaginal organ motion when IMRT technique is used. Several dosimetric studies demonstrating the potential benefit of pelvic IMRT for the postoperative treatment of gynecologic malignancies have been performed (2–11). These studies generally reveal that IMRT technique confers a number of dosimetric advantages over three-dimensional conformal radiotherapy (CRT) technique or four-field box, including bone marrow, bowel and bladder sparing, a reduction in the integral dose to normal organs, improved PTV target volume coverage, but at the expense of larger volumes receiving lower doses.
Intensity-modulated radiation therapy (IMRT) may be useful to reduce toxicity in gynecologic cancer patients requiring postoperative pelvic irradiation. This study was undertaken to quantify vaginal wall organ motion during the course of postoperative pelvic irradiation using pelvic IMRT.
Twenty-two consecutive patients treated with postoperative pelvic IMRT on helical tomotherapy had fiducial markers placed at the vaginal apex prior to simulation then daily megavoltage computed tomography (CT) scans for positioning. The daily positions of the fiducials were registered and measured in reference to the initial CT scan to quantify the degree of vaginal wall organ motion during the entire course of therapy.
The total motion of the fiducials center of mass (COM) was a median of 5.8 mm (range, 0.6–20.2 mm), and 95% of all COM positions fell within 15.7 mm of their original position. Directional margins of 3.1 mm along the right-left axis, 9.5 mm along the superoinferior axis, and of 12.1 mm along the anteroposterior axis encompassed the vaginal fiducials in 95% of treatments. Mean organ deformation for all patients was 3.9 mm, (range, 0–27.5 mm; standard deviation, 3.1 mm), with significant distortions of greater than 10 mm in 17% of secondary image sets.
These data suggest a planning target volume margin of 16 mm will account for maximal organ motion in the majority of gynecologic patients undergoing postoperative pelvic IMRT, and it may be possible to incorporate directional motion into the planning target volume margin.
Internal motion of the vagina after hysterectomy for gynaecological cancer
2011, Radiotherapy and Oncology
The purpose of this study was to investigate position changes of the vagina after hysterectomy for early stage cervical or endometrial cancer and their impact on CTV–PTV margins. We also studied their correlation with surrounding organ filling.
Fifteen patients underwent T2-weighted MR scans before and weekly during the course of their EBRT. The vaginal CTVs and the surrounding organs were delineated. PTV margins were derived from the boundaries of the CTVs in the main directions and correlated with changes in the volumes of organs at risk. Additionally we investigated the impact of margin sizes on CTV coverage.
The vaginal CTVs change their position in the pelvis during time with a maximum in anterior–posterior direction. The 95% confidence level was 2.3 cm into the anterior or posterior direction, 1.8 cm to left or right and 1.5 cm towards the cranial. With a homogenous 1.5 cm CTV–PTV margin ⩾5% inadequately covered vaginal CTV was seen in only 3.3% of the measurements. This increased to 20.6% with a margin of 1.0 cm. Concerning the impact of organ filling on vaginal position changes we found the only significant correlation with rectal volume and shift of the vagina towards anterior–posterior.
To accommodate the changes in the position of the vaginal CTV inhomogeneous PTV margins should be generated with the largest size in the anterior–posterior direction. The position shifts were only weakly related to the volume of the rectum and not at all to the volumes of other parts of the bowel and the bladder.

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Clinical investigationCervixFeasibility of dose escalation using intensity-modulated radiotherapy in posthysterectomy cervical carcinoma

Purpose

Methods and materials

Results

Conclusion

Introduction

Section snippets

Methods and materials

Results

Discussion

Conclusion

Gynecol Oncol

Lancet

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Gynecol Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Clinical investigation
Cervix
Feasibility of dose escalation using intensity-modulated radiotherapy in posthysterectomy cervical carcinoma