Medical Dosimetry
Volume 36, Issue 1 , Pages 35-40, Spring 2011

Conkiss: Conformal Kidneys Sparing 3D Noncoplanar Radiotherapy Treatment for Pancreatic Cancer As an Alternative to IMRT

  • Zsolt Sebestyén, M.Sc.

      Affiliations

    • University of Pécs, Institute of Oncotherapy, Pécs, Hungary
    • Corresponding Author InformationReprint requests to: Zsolt Sebestyén, M.Sc., H-7624 Pécs, Édesanyák útja 17, Hungary
    • ,
  • Péter Kovács, M.Sc.

      Affiliations

    • University of Pécs, Institute of Oncotherapy, Pécs, Hungary
    • ,
  • Ákos Gulybán, M.Sc.

      Affiliations

    • EORTC Headquarters, Brussels, Belgium
    • ,
  • Róbert Farkas, M.D.

      Affiliations

    • University of Pécs, Institute of Oncotherapy, Pécs, Hungary
    • ,
  • Szabolcs Bellyei, M.D., Ph.D.

      Affiliations

    • University of Pécs, Institute of Oncotherapy, Pécs, Hungary
    • ,
  • Gábor Liposits, M.D.

      Affiliations

    • University of Pécs, Institute of Oncotherapy, Pécs, Hungary
    • ,
  • András Szigeti, M.D., Ph.D.

      Affiliations

    • University of Pécs, Institute of Oncotherapy, Pécs, Hungary
    • ,
  • Olga Ésik, M.D., D.Sc.

      Affiliations

    • University of Pécs, Institute of Oncotherapy, Pécs, Hungary
    • ,
  • Katalin Dérczy, M.D.

      Affiliations

    • University of Pécs, Department of Radiology, Pécs, Hungary
    • ,
  • László Mangel, M.D., Ph.D.

      Affiliations

    • University of Pécs, Institute of Oncotherapy, Pécs, Hungary

Received 4 June 2009; accepted 10 November 2009. published online 25 January 2010.

Article Outline

Abstract 

When treating pancreatic cancer using standard (ST) 3D conformal radiotherapy (3D-CRT) beam arrangements, the kidneys often receive a higher dose than their probable tolerance limit. Our aim was to elaborate a new planning method that—similarly to IMRT—effectively spares the kidneys without compromising the target coverage. Conformal kidneys sparing (CONKISS) 5-field, noncoplanar plans were compared with ST plans for 23 consecutive patients retrospectively. Optimal beam arrangements were used consisting of a left- and right-wedged beam-pair and an anteroposterior beam inclined in the caudal direction. The wedge direction determination (WEDDE) algorithm was developed to adjust the adequate direction of wedges. The aimed organs at risk (OARs) mean dose limits were: kidney <12 Gy, liver <25 Gy, small bowels <30 Gy, and spinal cord maximum <45 Gy. Conformity and homogeneity indexes with z-test were used to evaluate and compare the different planning approaches. The mean dose to the kidneys decreased significantly (p < 0.05): left kidney 7.7 vs. 10.7 Gy, right kidney 9.1 vs. 11.7 Gy. Meanwhile the mean dose to the liver increased significantly (18.1 vs. 15.0 Gy). The changes in the conformity, homogeneity, and in the doses to other OARs were not significant. The CONKISS method balances the load among the OARs and significantly reduces the dose to the kidneys, without any significant change in the conformity and homogeneity. Using 3D-CRT the CONKISS method can be a smart alternative to IMRT to enhance the possibility of dose escalation.

Key Words: Pancreatic cancer, 3D conformal radiotherapy, Noncoplanar fields, Dosimetric comparison, IMRT

 

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Introduction 

Pancreatic cancer is the fourth leading cause of cancer mortality in the world.1, 2 The optimal strategy for treating these patients is still controversial because this disease is not curable using the existing treatment techniques. Several authors have already published the importance of different chemotherapies used as part of a chemoradiotherapy (CHRT) treatment of patients who present with unresectable, locally advanced pancreatic cancer. Considering these data, radiotherapy (RT) is widely used as part of the treatment strategy.1, 3, 4, 5, 6, 7

Delivering adequate radiation doses to the pancreas is limited by the presence of radiation-sensitive normal structures in the upper abdomen. These include the kidneys, liver, small bowels, stomach, and spinal cord.6

The 5-fluorouracil (FU)–based CHT combined with the standard (ST) 3D conformal RT treatment (3D-CRT) technique was used in our department.8 The disadvantage of the ST technique is that the kidneys often receive higher mean dose than their generally accepted tolerance limit. Our aim was to find a conformal treatment technique that delivers a lower dose to the kidneys than their tolerance limit—similar to intensity-modulated radiation therapy (IMRT),9 but taking minimal time and technical requirements.

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Methods and Materials 

Between February 2005 and August 2008, 23 consecutive patients in our department with locally advanced, unresectable pancreatic cancer were treated with ST 3D-CRT technique.8 The patient immobilization was done using individual vacuum cushion in supine position. During the RT procedure 10-mm increment computer tomography (CT) scans were taken with a Siemens Somatom CT (Siemens, Erlangen, Germany) scanner and transferred to our Precise Plan treatment planning system (TPS) (Elekta, PrecisePLAN 2.02/2.03, Atlanta GA). The prescribed dose was 45 Gy to the PTV in 1.8 Gy per fractions. During the planning process we followed the ICRU 50, 62 recommendations.10, 11

Contouring 

First, the primary gross tumor volume (GTV) and the clinical target volume (CTV) were defined. Organ motion and set-up errors were also considered, thus the planning target volume (PTV) was defined as CTV with a uniform margin of 15 mm. The clinically uninvolved regional lymphatics were not included into any of the target volumes. As organs at risk (OARs), the kidneys, liver, small bowels, and spinal cord were contoured on all CT images.

Planning priorities and OAR tolerance dose limits 

The main priority was to deliver the 45-Gy prescribed mean dose to the PTV homogeneously. The second priority was to keep the OARs' mean dose and percentage volume below their tolerance limits (Table 1).6, 9, 12, 13 The kidney and the spinal cord limit were respected with higher priority within the OARs.

Table 1. OAR tolerance limits⁎
Primary Goal
PTV CoverageV95–107% as High as Possible
Secondary Goals
OARMean Dose LimitVx limit
Kidney<12GyV20<30%
Liver<25GyV35<33%
Small bowel<30GyV45<10%
Spinal cord—V4=0%

Abbreviations: OAR = organ at risk; Vx (%) = percentage of total volume receiving × Gy.

⁎These are mainly institutional guidelines used in the literature.6, 9, 12, 13

ST 3D-CRT treatment planning 

The ST 3D-CRT plans consisted of 3 fields including an open anteroposterior (AP) and two opposed, wedged lateral 6-MV photon beams.8 The isocenter was defined to the geometrical center of the PTV. For generating MLC fields, the following shapes were used: 10-mm margin around the PTV from beam's eye view (BEV), except near the kidneys and the liver, where they were manually reduced to 3 and 8 mm, respectively. The beam-weights were optimized with the IMRT optimizing module of TPS to achieve 45 Gy mean dose to the PTV.

CONKISS planning method 

The baseline of the conformal kidneys sparing (CONKISS) 5-field beam arrangement was (Fig. 1): 1 AP-like beam with 40° gantry angle and 90° table angle (G40-T90) and 4 lateral fields: G270-T340, G90-T340, G270-T20, and G90-T20 followed by individual adjustment. The isocenter was moved from the center of the PTV anteriorly considering the following:

1.Isocenter should not be closer than 1 cm to the PTV border, for adequate dose calculation

2.The AP-like beam is not causing gantry-patient/table collision.

Individual beam direction adjustment—equal area overlapping principle 

The gantry angles of the lateral fields were adjusted so that from their BEV the same kidney areas—from both of the kidneys—were overlapped in the PTV. The table angle of the AP-like beam was adjusted so that again the same areas of the kidneys were overlapped in the PTV.

Wedge direction adjustment 

A 60° wedge was used in all 4 lateral beams. In this article the direction of a wedge is defined as the direction where the wedge has greater blocking effect. The wedges of the 2 lateral fields closer to the AP-like beam were directed to the other lateral beams on the same side. In the other 2 lateral beams the wedges were directed to the AP-like beam (Fig. 1).

Wedge direction determination algorithm 

The wedge direction determination algorithm (WEDDE) algorithm was made to determine the proper collimator angle for the required wedge direction (Fig. 2). It used a polar coordinate system from the table point of view (POV) (Fig. 2). In this POV the gantry could move on a unit-radius sphere, limited by the physical extensions of the gantry, table, and patient.

  • View full-size image.
  • Fig. 2. 

    The model used in the WEDDE algorithm, where WB represents the gantry position of the wedged beam, B represents the gantry position of the beam where the wedge in WB will direct, O is the place of isocentre, and AP represents the gantry position of the AP beam.

Determination of the required collimator angle 

The initial direction of the wedges was always the upper direction—when the wedge was directed to an AP beam. The algorithm converted the polar coordinates of the points on Fig. 2 to Cartesian coordinates. We determined the equation of the 2 planes defined by points AP, O, WB and O, WB, B (Fig. 2). Then we determined their dihedral angle (the angle between these two planes)—what is the required collimator rotation angle to direct the wedge to another beam. Using these principles, our algorithm determined the exact collimator angle in 4 lateral fields. This method can be applied in all similar treatment planning situations.

MLC setting adjustment 

The generation of MLC fields and the beam weight optimization was done in the same way as in case of the ST technique. When the mean dose to the kidneys was less than 50% of their tolerance limit, the previously reduced margins were increased either until the mean kidney dose reached 66% of the tolerance limit or until it reached the original value. The procedure was named the “1/2→2/3 rule”.

To further increase PTV homogeneity and to reduce the maximum dose value, a second segment was used in the AP-like beam that excluded the highest 2–3% dose cloud from BEV, similarly to Gulybán et al.14

Figure 3 shows the workflow of the whole CONKISS method.

Plan evaluation and comparison 

The conformity of the plans was evaluated using the conformation number (CN) in the following formula:

(1)
where VT,PI is the volume of PTV receiving at least the prescription dose, VPI is the volume enclosed by the prescription isodose, and VT is the PTV.15, 16

The homogeneity was evaluated in 2 different ways using the cumulative dose volume histogram (DVH): First according to ICRU 50, 62,10, 11 where the V95–107% represents the percentage of PTV between 95–107% of the prescribed dose; second, using the D95–5%17:

(2)
where D5%, and D95% were the doses received by 5% and 95% of the PTV volume, and PI is the prescribed isodose.

With regard to the OARs, we evaluated the mean dose to the kidneys, liver, and small bowel; the maximum dose to spinal cord; and the percentage of kidneys and total kidney volumes receiving 20 Gy (V20), liver V35, and small bowel V45.6, 9 To compare the 2 techniques, relative evaluation was performed using the percentage OAR dose reduction values.18

Statistical analyses 

All data are presented in mean dose ± standard deviation and as percentage of tolerance limit. Two-tailed t significance tests were performed to compare the results of the 2 techniques. The 5% probability level (p < 0.05) was considered to be statistically significant.

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Results 

PTV coverage 

The mean PTV volume was 657.8 cm3 (range 296–1080). The CONKISS plans resulted in a better V95–107% and D95–5% homogeneity and in a slightly worse conformity (Table 2). None of these differences was statistically significant.

Table 2. ST—CONKISS comparison10, 11, 19, 20, 21
ST ± SDCONKISS ± SDpReduction in % (CONKISS/ST)
PTV
V95–107%— homogeneity95.5±2.696.4±2.1NS—
D95–5%—homogeneity8.4±2.77.6±2.1NS—
CN—conformity0.656±0.060.636±0.06NS—
OAR
Left kidney
Mean dose (Gy)10.7±4.27.7±2.8<0.00828.0
V20(%)11.5±10.08.5±6.7NS—
Right kidney
Mean dose (Gy)11.7±5.09.1±3.7<0.0522.2
V20 (%)12.8±12.69.7±7.9NS—
Total kidney
Mean dose (Gy)11.1±4.18.4±3.1<0.0224.3
V20(%)12.0±10.19.0±7.1NS—
Liver
Mean dose (Gy)15.0±3.818.1±3.3<0.008–20.7
V35(%)13.8±7.812.1±6.3NS—
Small bowel
Mean dose (Gy)11.9±6.214.6±6.4NS—
V45(%)4.3±3.85.1±5.1NS—
Spinal cord
Maximum (Gy)15.7±3.015.2±4.8NS—

Abbreviations: OAR = organs at risk; PTV = planning target volume; ST 3D-CRT = standard 3D conformal radiotherapy treatment (technique); CONKISS = conformal kidneys sparing (method); Vx (%) = percentage of total volume receiving × Gy; NS = not significant (p > 0.05).

Dose to OARs 

With the ST plans, the mean dose to the right kidney exceeded its defined tolerance limit in 10 cases, for the left kidney in 8 cases, and for the total kidney in 9 caes. With the CONKISS method, this number was reduced to 4, 2, and 3, respectively. All of the other OARs' mean doses—liver V35, small bowel V45—and the spinal cord maximum doses were for both of the techniques under their tolerance limits.

Comparison of the OARs' mean doses and percentage volumes is shown in Table 2. With the CONKISS technique, the mean left, right, and total kidney doses were significantly reduced. The mean dose to the liver significantly increased, whereas the liver V35 decreased. The differences between the other mean doses and percentage volumes were not statistically significant.

With the CONKISS method, the following mean dose reductions were achieved: left kidney 28.0%, right kidney 22.2%, total kidney 24.3%. The mean dose to the liver increased by 20.7%. Concerning the percentage volumes, the reduction was 26.1, 24.2, 25.0, and 12.3%, for the left, right, and total kidney and for the liver, respectively (Table 2). For the CONKISS plans, the mean doses to the kidneys and to the liver in percentages of their tolerance limits were similar: left kidney 64%, right kidney 76%, total kidney 70%, and liver 72%. The CONKISS method allowed balancing the doses to the kidneys and to the liver compared wth the ST technique, where these percentages were 89, 98, 93, and 60%, respectively (Fig. 4). The doses to the other OARs remained under ∼50% of their tolerance limits and none of these changes were statistically significant.

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Discussion 

While developing the CONKISS method, we applied retrospectively more than 30 different 3-field to 7-field, mainly noncoplanar beam arrangements with different photon energies. Some of them were better only for a few patients similar to other reported methods.18 The previous experiences were used to develop the CONKISS method, which had better results for all of our patients. Similarly to Higgins et al.,22 we found that the 6-MV plans were superior to the 18-MV plans. Osborne et al.23 reported a comparison of noncoplanar and coplanar techniques to treat pancreatic cancer based on normal tissue complication probability (NTCP) and on total weighted equivalent uniform dose (EUD) calculations. They found that noncoplanar techniques have an overall benefit compared with coplanar techniques. Our experiences similarly showed that coplanar beam arrangements were worse than the noncoplanar CONKISS method.

The lower SD values of the CONKISS method show that the reproduction of its result is easier than that of the ST technique.

Advantages of lateral beam directions 

Based on various reports,24, 25 the respiration-induced movement of the pancreas and the OARs in the AP direction is the least compared with the movements in other directions: the movements of the pancreas in the craniocaudal direction an average 21.6 mm, in the LR direction an average 12.0 mm, and in the AP direction an average 6.0 mm.24 The use of mostly lateral fields allowed a higher probability in delivering the planned dose to the PTV and to the OARs. Another advantage was that the kidneys received the least dose when the lateral fields went through the least kidney area seen from BEV.

CONKISS vs. IMRT comparison 

Brown et al.9 compared 2 IMRT and 1 conformal technique for 15 patients retrospectively. The average volume of their PTV was similar: 678.2 cm3 (PTV1). Their prescription dose was different: 45 Gy to the PTV (PTV1); 59.4 Gy to the PTV-0.5 cm (PTV2); and 64.8 Gy to the PTV-1 cm (PTV3). To compare the results, we increased the number of fractions to 64.8 Gy without reducing the original PTV, thus the doses to the OARs were considerably overestimated. Table 3 shows the comparison of the OAR percentage volumes.

Table 3. Comparison of the OAR percentage volumes for the 3D-CRT, IMRTi, IMRTs, ST 3D-CRT, and CONKISS plans for a total 64.8 Gy dose
Tolerance Limit3D-CRTIMRTsIMRTiST 3D-CRTCONKISS
% of 3D-CRT% of 3D-CRT% of ST 3D-CRT
PTV mean dose 45+9+5.4+9 Gy64.8 Gy
Left kidney V12 (%)5010.813.810.529.017.9
1289762
Right kidney V12 (%)5062.949.035.633.022.4
785768
Total kidney V12 (%)5035.427.722.330.619.9
786365
Liver V35 (%)3324.49.67.531.134.4
3931111
Small bowel V45 (%)106.13.32.119.018.2
543496

Abbreviations: PTV = planning target volume; ST 3D-CRT = standard 3D conformal radiotherapy treatment (technique); CONKISS = conformal kidneys sparing (method); IMRT = intensity-modulated radiotherapy; IMRTi = simultaneous integrated IMRT boost; IMRTs = sequential IMRT boosting;9 Vx (%) = percentage of total volume receiving × Gy.

In our plans, the V20 for the total kidney was still smaller than for the IMRTi and IMRTs techniques (19.9% for the CONKISS plans and 27.7 and 22.3% for the IMRTs and IMRTi plans, respectively).

Balancing the dose to the OARs 

According to Wilkowski et al., concurrent chemotherapy can significantly reduce the tolerance level of the kidneys; therefore they aimed not to expose 30% of a kidney to more than 20 Gy.12 If one kidney is not functioning well than it can be sacrificed to spare the other well-functioning kidney as much as possible. With the 1/2→2/3 rule, the CONKISS method takes into consideration what could be more important: lower dose to both or only one kidney or better PTV coverage.

The issue concerning the liver seems to be controversial. On one hand, Dawson et al.—based on NTCP estimation—indicated higher tolerance of the liver tissue: just 5% risk of radiogenic liver damage at 47 Gy, or 31 Gy for 66% or 100% of the liver volume,13 respectively. On the other hand, according to Wilkowski et al., the dose tolerance limit of the liver should be further reduced as a result of concurrent chemotherapy to a maximum 25 Gy, or 37.5 Gy for 50% or 25% of the liver volume, respectively.12 Based on a liver function test, a patient-specific liver dose tolerance limit should be considered.

Using the CONKISS method the dose to the kidneys and the liver will be almost the same in percentage of their tolerance limits: left kidney 64%, right kidney 76%, total kidney 70%, liver 72%; thus the CONKISS method makes a balance between the kidneys and the liver.

The fact that the mean dose to the liver increased while its V35 decreased shows that the increase in the overall biological effect, because of increased mean liver dose, would presumably not be so severe because simultaneously the liver V35 decreased.

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Conclusion 

The CONKISS method is an effective and individualizable treatment planning method to significantly reduce the dose to kidneys, without any significant change in the conformity and homogeneity. This OAR sparing could potentially allow either dose escalation, thus further enhancing the loco regional control or further decreasing the possibility of OAR related side effects, thus ensuring the possibility to apply any further chemotherapy regimens. The WEDDE algorithm gives possibility to develop other new conformal planning techniques to improve OAR sparing, similarly to the CONKISS method. Using 3D-CRT, the CONKISS method can be a simple, smart alternative to IMRT.

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Acknowledgment 

The authors thank Markus Alber, Judit Boda-Heggemann, Pierre Pilette, and Katalin Hideghety for the critical reading of the manuscript.

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References 

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PII: S0958-3947(09)00127-7

doi:10.1016/j.meddos.2009.11.001

Medical Dosimetry
Volume 36, Issue 1 , Pages 35-40, Spring 2011

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