Adaptive radiotherapy strategies for pelvic tumors – a systematic review of clinical implementations

Figures & data

Table 1. Results from the PubMed searches and paper selection.

Site	Pubmed search hits	Pubmed hits after title and abstract screening	Pubmed hits after full paper screening (clinical/simulation)	Final studies included the review
Prostate	341	177	33 (8/25)	45 (11[11–21]/34[22,58–62,67–94])
Gynecological	200	72	22 (14/8)	28 (19 [23–41] /9 [63,65,66,95–100])
Bladder	162	100	17 (10/7)	19 (12 [45–56] /7 [64,101–106])
Ano-rectal	194	114	2 (1/1)	2 (1[57]/1 [107])
Total	897	463	74 (33/41)	94 (43/51)

Figure 1. Accumulation of clinical implementation and simulation studies for prostate (dark gray), gynecological (light gray), bladder (gray) and ano-rectal (black) cancer. Date of enrollment of the first patient were denoted for the clinical implementations (solid lines) and date of acceptance for publication of the simulation studies (dotted lines).

Table 2. Applied plan adaptations and reported dosimetric gains in the clinically implemented studies for external beam radiotherapy.

Study description			ART workflow	Reported dosimetric gain
Study	Site	Pts.
Beaumont (1997) [13]	Prost.	10	Offline MLC re-shaping/forward re-plan	N/A
Beaumont (1997–2006) [11,12,14–16]	Prost.	962	Offline re-plan with target motion-adapted PTV	PTV reduction of 24% (based on 150 pts). Dose escalation of 5% (CRT) and 7% (IMRT) (based on 150 pts)
Toronto (2001–) [19]	Prost.	33	Offline re-plan of boost with adapted PTV	N/A
Amsterdam (2005) [17]	Prost.	23	Offline re-plan with motion-adapted PTV and rectum	PTV reduction of 29%. OAR sparing with rectum V65 reduced by 19%, anal wall average dose reduced by 4.8 Gy
Pardubice (2008–2012) [18]	Prost.	201	Offline re-plan with adapted PTV	CTV coverage was 99% with individual margins (based on 446 pre-fr. CBCTs from 76 pts)
Salzburgh (2009–) [20]	Prost.	39	Online forward re-planning of intra-fractional motion	PTV reduction of 57% in exemplified patient as compared to IGRT only. Full CTV coverage of intra-fraction motion in 79% of pts
San Fransisco (2010) [21]	Prost.	1	Online plan selection	Reduced coverage with CTV prost D95 ≥ 95% in 11/17 fr. with ART and 17/17 w/o ART. Increased coverage of CTV lymph node with D95 ≥ 95% in 17/17 fr. with ART and 13/17 w/o ART. Increased OAR sparing with kidney V20 ≤ 15 Gy in 13/17 fr. with ART and 2/17 w/o ART
Rotterdam (2011–) [41]	Cervix	64	Online plan selection	Reduction of bowel V99 by 26% and 29% for the (11) pts with 2 IMRT plans in the library as compared to the back-up plan
Leeds (1989–1990) [45]	Bladd.	90	Offline re-plan with PTV or field adaptation	N/A
Manchester (1993) [46]	Bladd.	30	Offline re-plan to new CTV position	N/A
Multi-center the Netherlands (2003–2004) [56]	Bladd.	21	Offline re-planning with adapted ITV	PTV reduction of 40%. CTV coverage in 95% of follow-up CTs with CTV fully inside the PTV as compared to 90% w/o ART
Melbourne (2007–2008) [47,48]	Bladd.	27	Online plan selection	Increased CTV coverage with V95 < 99% of CTV in 2.7% of fr. compared to 4.8% w/o ART. OAR sparing with normal tissue V45 reduced by 29%
Mumbay (2008–2009) [53]	Bladd.	10	Online plan selection	N/A
Eindhoven (2008–2011) [54]	Bladd.	20	Online plan selection	N/A
Helsinki (2009–2012) [52,55]	Bladd.	10	Online plan selection	Decreased coverage with CTV Dmin <95% of prescribed dose in 11% of fr. with ART and 4% w/o ART. Increased OAR sparing with intestinal cavity V45 reduced by 155 cm^3 (SD = 74 cm^3) (contribution of partial bladder boost included)
Sutton (2009–2011) [49]	Bladd.	25	Online plan selection	Reduced PTV volume of 219 cm^3
Multi-center Australia (2010–2013) [50]	Bladd.	49	Online plan selection	N/A
Multi-center Denmark (2012–2013) [51]	Bladd.	20	Online plan selection	Reduced PTV of 30% or 183 cm^3. OAR sparing with intestinal cavity V45 reduced by 100 cm^3 and rectum V30 reduced by 10% (bladder only)
Milan (2009–2012) [57]	Rect.	25	Offline re-planning of dose-escalated boost	Dose escalation to the residual tumor (MRI) of 8.4 Gy EQD2 (18%)

Prost: prostate; bladd: bladder; rect: ano-rectum; pts: patients; N/A: not available; fr: fraction; w/o: without; OAR: organs at risk; SD: standard deviation.

Table 3. Applied plan adaptations and reported dosimetric gains for adaptation in the clinically implemented studies for a combination of brachy- and external beam radiotherapy.

Study description			ART workflow	Reported dosimetric gain
Study	Site	Pts.
Vienna (1993–2000) [23,26]	Cervix	181 + 73	Online re-plan based on visual examination of in treatment CTs	N/A
Vienna (1997) [24]	Endo.	16	Online re-plan based on visual examination of in treatment CT/MRI	N/A
Vienna (1999–2006) [25]	Vaginal	13	Online re-plan based on regression seen in treatment MRI	N/A
Vienna (2001–2008) [26,27]	Cervix	156	Online re-plan based on regression seen in treatment MRI	Dose escalation from D90 of 90 Gy (SD = 15 Gy) to D90 of 94 Gy (SD = 10 Gy)
Cambridge (2005–2007) [28]	Cervix	28	Online re-plan based on regression seen in treatment CTs	N/A
Villejuif (2004–2006) [36]	Cervix	45	Following Gyne GEC-ESTRO recommendations	N/A
Villejuif (2004–2009) [30]	Cervix	163	Following Gyne GEC-ESTRO recommendations	N/A
Aarhus (2005–2011) [29]	Cervix	140	Following Gyne GEC-ESTRO recommendations	CTV coverage of D90 ≥ 85 Gy and OAR constraints fulfilled in 80% of pts. compared to 27% with no ART (evaluated for 70 pts)
Multi-center France  (2005–2007) [30,37]	Cervix	163 + 117	Following Gyne GEC-ESTRO recommendations	The 60 Gy isodose volume reduced by 18% with ART for intermediate-staged pts and increased by 24% with ART for advanced staged pts
Utrecht (2006–2008) [34]	Cervix	46	Following Gyne GEC-ESTRO recommendations	N/A
Mumbai (2006–2007) [35]	Cervix	24	Following Gyne GEC-ESTRO recommendations	N/A
Leiden (2007–2012) [38]	Cervix	83	Following Gyne GEC-ESTRO recommendations	N/A
Toronto (N/A) [31]	Cervix	43	Following Gyne GEC-ESTRO recommendations	N/A
Pittsburgh (2007–2010) [39]	Cervix	44	Following Gyne GEC-ESTRO recommendations	N/A
Aarhus (2009–2012) [40]	Cervix	3	Following Gyne GEC-ESTRO recommendations & IMRT boost patched to BT dose distribution	N/A
Aarhus (2005–2010) [32]	Vaginal, endo., cervix	28	Following Gyne GEC-ESTRO recommendations	N/A
Aarhus (2006–2013) [33]	Endo.	43	Following Gyne GEC-ESTRO recommendations	N/A

Endo: endometrial; gyne: gynecological; pts: patients; N/A: not available; SD: standard deviation; OAR: organs at risk.

Figure 2. The number of prostate (dark gray), gynecological (light gray), bladder (gray) and ano-rectal (black) patients treated with the different categories of ART workflows. Patients treated with brachytherapy additionally marked with striped pattern.

Figure 3. Different categories of the implemented and the simulated ART workflows: online re-planning (blue), offline re-planning (red), online plan selection (turquoise), online MLC/field alteration (green), offline MLC/field alteration (violet). The workflows are plotted as percentage of the total number of either implementation or simulation workflows. Studies concerning brachytherapy additionally marked with striped pattern. clin: clinical; sim: simulation; gyne: gynecological.

Figure 4. Changes in evaluation points with ART as compared to the conventional strategy for prostate (dark gray diamonds), gynecological (light gray triangles), bladder (gray circles) and ano-rectal (black squares). Changes in target coverage is displayed in top left (A), to the rectum top right (B), bladder lower left (C) and the bowel cavity and other normal tissues lower right (D). Studies concerning brachytherapy additionally marked with striped pattern. BA: bony anatomy; GM: gold markers; BT: brachytherapy; fxs: fractions.

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