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1.  Radiobiological evaluation of forward and inverse IMRT using different fractionations for head and neck tumours 
Purpose
To quantify the radiobiological advantages obtained by an Improved Forward Planning technique (IFP) and two IMRT techniques using different fractionation schemes for the irradiation of head and neck tumours. The conventional radiation therapy technique (CONVT) was used here as a benchmark.
Methods
Seven patients with head and neck tumours were selected for this retrospective planning study. The PTV1 included the primary tumour, PTV2 the high risk lymph nodes and PTV3 the low risk lymph nodes. Except for the conventional technique where a maximum dose of 64.8 Gy was prescribed to the PTV1, 70.2 Gy, 59.4 Gy and 50.4 Gy were prescribed respectively to PTV1, PTV2 and PTV3. Except for IMRT2, all techniques were delivered by three sequential phases. The IFP technique used five to seven directions with a total of 15 to 21 beams. The IMRT techniques used five to nine directions and around 80 segments. The first, IMRT1, was prescribed with the conventional fractionation scheme of 1.8 Gy per fraction delivered in 39 fractions by three treatment phases. The second, IMRT2, simultaneously irradiated the PTV2 and PTV3 with 59.4 Gy and 50.4 Gy in 28 fractions, respectively, while the PTV1 was boosted with six subsequent fractions of 1.8 Gy. Tissue response was calculated using the relative seriality model and the Poisson Linear-Quadratic-Time model to simulate repopulation in the primary tumour.
Results
The average probability of total tumour control increased from 38% with CONVT to 80% with IFP, to 85% with IMRT1 and 89% with IMRT2. The shorter treatment time and larger dose per fraction obtained with IMRT2 resulted in an 11% increase in the probability of control in the PTV1 with respect to IFP and 7% relatively to IMRT1 (p < 0.05). The average probability of total patient complications was reduced from 80% with CONVT to 61% with IFP and 31% with IMRT. The corresponding probability of complications in the ipsilateral parotid was 63%, 42% and 20%; in the contralateral parotid it was 50%, 20% and 9%; in the oral cavity it was 2%, 15% and 4% and in the mandible it was 1%, 5% and 3%, respectively.
Conclusions
A significant improvement in treatment outcome was obtained with IMRT compared to conventional radiation therapy. The practical and biological advantages of IMRT2, employing a shorter treatment time, may outweigh the small differences obtained in the organs at risk between the two IMRT techniques. This technique is therefore presently being used in the clinic for selected patients with head and neck tumours. A significant improvement in the quality of the dose distribution was obtained with IFP compared to CONVT. Thus, this beam arrangement is used in the clinical routine as an alternative to IMRT.
doi:10.1186/1748-717X-5-57
PMCID: PMC2907388  PMID: 20569482
2.  Radiobiological Impact of Planning Techniques for Prostate Cancer in Terms of Tumor Control Probability and Normal Tissue Complication Probability 
Background:
The radiobiological models describe the effects of the radiation treatment on cancer and healthy cells, and the radiobiological effects are generally characterized by the tumor control probability (TCP) and normal tissue complication probability (NTCP).
Aim:
The purpose of this study was to assess the radiobiological impact of RapidArc planning techniques for prostate cancer in terms of TCP and normal NTCP.
Subjects and Methods:
A computed tomography data set of ten cases involving low-risk prostate cancer was selected for this retrospective study. For each case, two RapidArc plans were created in Eclipse treatment planning system. The double arc (DA) plan was created using two full arcs and the single arc (SA) plan was created using one full arc. All treatment plans were calculated with anisotropic analytical algorithm. Radiobiological modeling response evaluation was performed by calculating Niemierko's equivalent uniform dose (EUD)-based Tumor TCP and NTCP values.
Results:
For prostate tumor, the average EUD in the SA plans was slightly higher than in the DA plans (78.10 Gy vs. 77.77 Gy; P = 0.01), but the average TCP was comparable (98.3% vs. 98.3%; P = 0.01). In comparison to the DA plans, the SA plans produced higher average EUD to bladder (40.71 Gy vs. 40.46 Gy; P = 0.03) and femoral heads (10.39 Gy vs. 9.40 Gy; P = 0.03), whereas both techniques produced NTCP well below 0.1% for bladder (P = 0.14) and femoral heads (P = 0.26). In contrast, the SA plans produced higher average NTCP compared to the DA plans (2.2% vs. 1.9%; P = 0.01). Furthermore, the EUD to rectum was slightly higher in the SA plans (62.88 Gy vs. 62.22 Gy; P = 0.01).
Conclusion:
The SA and DA techniques produced similar TCP for low-risk prostate cancer. The NTCP for femoral heads and bladder was comparable in the SA and DA plans; however, the SA technique resulted in higher NTCP for rectum in comparison with the DA technique.
doi:10.4103/2141-9248.129023
PMCID: PMC3991934  PMID: 24761232
Equivalent uniform dose; Normal tissue complication probability; Prostate cancer; RapidArc planning; Tumor control probability
3.  Dose distribution and tumor control probability in out-of-field lymph node stations in intensity modulated radiotherapy (IMRT) vs 3D-conformal radiotherapy (3D-CRT) of non-small-cell lung cancer: an in silico analysis 
Background
The advent of IMRT and image-guided radiotherapy (IGRT) in combination with involved-field radiotherapy (IF-RT) in inoperable non-small-cell lung cancer results in a decreased incidental dose deposition in elective nodal stations. While incidental nodal irradiation is considered a relevant by-product of 3D-CRT to control microscopic disease this planning study analyzed the impact of IMRT on dosimetric parameters and tumor control probabilities (TCP) in elective nodal stations in direct comparison with 3D-CRT.
Methods and materials
The retrospective planning study was performed on 41 patients with NSCLC (stages II-III). The CTV was defined as the primary tumor (GTV + 3 mm) and all FDG-PET-positive lymph node stations. As to the PTV (CTV + 7 mm), both an IMRT plan and a 3D-CRT plan were established. Plans were escalated until the pre-defined dose-constraints of normal tissues (spinal cord, lung, esophagus and heart) were reached. Additionally, IMRT plans were normalized to the total dose of the corresponding 3D-CRT. For two groups of out-of-field mediastinal node stations (all lymph node stations not included in the CTV (LNall_el) and those directly adjacent to the CTV (LNadj_el)) the equivalent uniform dose (EUD) and the TCP (for microscopic disease a D50 of 36.5 Gy was assumed) for the treatment with IMRT vs 3D-CRT were calculated.
Results
In comparison, a significantly higher total dose for the PTV could be achieved with the IMRT planning as opposed to conventional 3D-CRT planning (74.3 Gy vs 70.1 Gy; p = 0.03). In identical total reference doses, the EUD of LNadj_el is significantly lower with IMRT than with 3D-CRT (40.4 Gy vs. 44.2 Gy. P = 0.05) and a significant reduction of TCP with IMRT vs 3D-CRT was demonstrated for LNall_el and LNadj_el (12.6 % vs. 14.8 %; and 23.6 % vs 27.3 %, respectively).
Conclusions
In comparison with 3D-CRT, IMRT comes along with a decreased EUD in out-of-field lymph node stations. This translates into a statistically significant decrease in TCP-values. Yet, the combination of IF-RT and IMRT leads to a significantly better sparing of normal tissues and higher total doses whereas the potential therapeutic drawback of decreased incidental irradiation of elective lymph nodes is moderate.
doi:10.1186/s13014-015-0485-6
PMCID: PMC4554351  PMID: 26292716
4.  Dosimetric comparison of standard three-dimensional conformal radiotherapy followed by intensity-modulated radiotherapy boost schedule (sequential IMRT plan) with simultaneous integrated boost–IMRT (SIB IMRT) treatment plan in patients with localized carcinoma prostate 
Aims:
Dosimeteric and radiobiological comparison of two radiation schedules in localized carcinoma prostate: Standard Three-Dimensional Conformal Radiotherapy (3DCRT) followed by Intensity Modulated Radiotherapy (IMRT) boost (sequential-IMRT) with Simultaneous Integrated Boost IMRT (SIB-IMRT).
Material and Methods:
Thirty patients were enrolled. In all, the target consisted of PTV P + SV (Prostate and seminal vesicles) and PTV LN (lymph nodes) where PTV refers to planning target volume and the critical structures included: bladder, rectum and small bowel. All patients were treated with sequential-IMRT plan, but for dosimetric comparison, SIB-IMRT plan was also created. The prescription dose to PTV P + SV was 74 Gy in both strategies but with different dose per fraction, however, the dose to PTV LN was 50 Gy delivered in 25 fractions over 5 weeks for sequential-IMRT and 54 Gy delivered in 27 fractions over 5.5 weeks for SIB-IMRT. The treatment plans were compared in terms of dose–volume histograms. Also, Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP) obtained with the two plans were compared.
Results:
The volume of rectum receiving 70 Gy or more (V > 70 Gy) was reduced to 18.23% with SIB-IMRT from 22.81% with sequential-IMRT. SIB-IMRT reduced the mean doses to both bladder and rectum by 13% and 17%, respectively, as compared to sequential-IMRT. NTCP of 0.86 ± 0.75% and 0.01 ± 0.02% for the bladder, 5.87 ± 2.58% and 4.31 ± 2.61% for the rectum and 8.83 ± 7.08% and 8.25 ± 7.98% for the bowel was seen with sequential-IMRT and SIB-IMRT plans respectively.
Conclusions:
For equal PTV coverage, SIB-IMRT markedly reduced doses to critical structures, therefore should be considered as the strategy for dose escalation. SIB-IMRT achieves lesser NTCP than sequential-IMRT.
doi:10.4103/0970-1591.102707
PMCID: PMC3507400  PMID: 23204659
Carcinoma prostate; intensity-modulated radiotherapy; normal tissue complication probability; simultaneous integrated boost; sequential intensity-modulated radiotherapy; tumor control probability
5.  Radiobiological impact of dose calculation algorithms on biologically optimized IMRT lung stereotactic body radiation therapy plans 
Background
The aim of this study is to evaluate the radiobiological impact of Acuros XB (AXB) vs. Anisotropic Analytic Algorithm (AAA) dose calculation algorithms in combined dose-volume and biological optimized IMRT plans of SBRT treatments for non-small-cell lung cancer (NSCLC) patients.
Methods
Twenty eight patients with NSCLC previously treated SBRT were re-planned using Varian Eclipse (V11) with combined dose-volume and biological optimization IMRT sliding window technique. The total dose prescribed to the PTV was 60 Gy with 12 Gy per fraction. The plans were initially optimized using AAA algorithm, and then were recomputed using AXB using the same MUs and MLC files to compare with the dose distribution of the original plans and assess the radiobiological as well as dosimetric impact of the two different dose algorithms. The Poisson Linear-Quadatric (PLQ) and Lyman-Kutcher-Burman (LKB) models were used for estimating the tumor control probability (TCP) and normal tissue complication probability (NTCP), respectively. The influence of the model parameter uncertainties on the TCP differences and the NTCP differences between AAA and AXB plans were studied by applying different sets of published model parameters. Patients were grouped into peripheral and centrally-located tumors to evaluate the impact of tumor location.
Results
PTV dose was lower in the re-calculated AXB plans, as compared to AAA plans. The median differences of PTV(D95%) were 1.7 Gy (range: 0.3, 6.5 Gy) and 1.0 Gy (range: 0.6, 4.4 Gy) for peripheral tumors and centrally-located tumors, respectively. The median differences of PTV(mean) were 0.4 Gy (range: 0.0, 1.9 Gy) and 0.9 Gy (range: 0.0, 4.3 Gy) for peripheral tumors and centrally-located tumors, respectively. TCP was also found lower in AXB-recalculated plans compared with the AAA plans. The median (range) of the TCP differences for 30 month local control were 1.6 % (0.3 %, 5.8 %) for peripheral tumors and 1.3 % (0.5 %, 3.4 %) for centrally located tumors. The lower TCP is associated with the lower PTV coverage in AXB-recalculated plans. No obvious trend was observed between the calculation-resulted TCP differences and tumor size or location. AAA and AXB yield very similar NTCP on lung pneumonitis according to the LKB model estimation in the present study.
Conclusion
AAA apparently overestimates the PTV dose; the magnitude of resulting difference in calculated TCP was up to 5.8 % in our study. AAA and AXB yield very similar NTCP on lung pneumonitis based on the LKB model parameter sets we used in the present study.
doi:10.1186/s13014-015-0578-2
PMCID: PMC4724090  PMID: 26800883
Combined dose-volume and biologically optimized IMRT; AAA and AXB dose calculation algorithms; TCP; NTCP; Fractioned stereotactic radiotherapy; Non-small-cell lung cancer
6.  Rotational IMRT techniques compared to fixed gantry IMRT and Tomotherapy: multi-institutional planning study for head-and-neck cases 
Background
Recent developments enable to deliver rotational IMRT with standard C-arm gantry based linear accelerators. This upcoming treatment technique was benchmarked in a multi-center treatment planning study against static gantry IMRT and rotational IMRT based on a ring gantry for a complex parotid gland sparing head-and-neck technique.
Methods
Treatment plans were created for 10 patients with head-and-neck tumours (oropharynx, hypopharynx, larynx) using the following treatment planning systems (TPS) for rotational IMRT: Monaco (ELEKTA VMAT solution), Eclipse (Varian RapidArc solution) and HiArt for the helical tomotherapy (Tomotherapy). Planning of static gantry IMRT was performed with KonRad, Pinnacle and Panther DAO based on step&shoot IMRT delivery and Eclipse for sliding window IMRT. The prescribed doses for the high dose PTVs were 65.1Gy or 60.9Gy and for the low dose PTVs 55.8Gy or 52.5Gy dependend on resection status. Plan evaluation was based on target coverage, conformity and homogeneity, DVHs of OARs and the volume of normal tissue receiving more than 5Gy (V5Gy). Additionally, the cumulative monitor units (MUs) and treatment times of the different technologies were compared. All evaluation parameters were averaged over all 10 patients for each technique and planning modality.
Results
Depending on IMRT technique and TPS, the mean CI values of all patients ranged from 1.17 to 2.82; and mean HI values varied from 0.05 to 0.10. The mean values of the median doses of the spared parotid were 26.5Gy for RapidArc and 23Gy for VMAT, 14.1Gy for Tomo. For fixed gantry techniques 21Gy was achieved for step&shoot+KonRad, 17.0Gy for step&shoot+Panther DAO, 23.3Gy for step&shoot+Pinnacle and 18.6Gy for sliding window.
V5Gy values were lowest for the sliding window IMRT technique (3499 ccm) and largest for RapidArc (5480 ccm). The lowest mean MU value of 408 was achieved by Panther DAO, compared to 1140 for sliding window IMRT.
Conclusions
All IMRT delivery technologies with their associated TPS provide plans with satisfying target coverage while at the same time respecting the defined OAR criteria. Sliding window IMRT, RapidArc and Tomo techniques resulted in better target dose homogeneity compared to VMAT and step&shoot IMRT. Rotational IMRT based on C-arm linacs and Tomotherapy seem to be advantageous with respect to OAR sparing and treatment delivery efficiency, at the cost of higher dose delivered to normal tissues. The overall treatment plan quality using Tomo seems to be better than the other TPS technology combinations.
doi:10.1186/1748-717X-6-20
PMCID: PMC3050734  PMID: 21338501
7.  Simultaneous modulated accelerated radiation therapy for esophageal cancer: A feasibility study 
World Journal of Gastroenterology : WJG  2014;20(38):13973-13980.
AIM: To establish the feasibility of simultaneous modulated accelerated radiation therapy (SMART) in esophageal cancer (EC).
METHODS: Computed tomography (CT) datasets of 10 patients with upper or middle thoracic squamous cell EC undergoing chemoradiotherapy were used to generate SMART, conventionally-fractionated three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiation therapy (cf-IMRT) plans, respectively. The gross target volume (GTV) of the esophagus, positive regional lymph nodes (LN), and suspected lymph nodes (LN±) were contoured for each patient. The clinical target volume (CTV) was delineated with 2-cm longitudinal and 0.5- to 1.0-cm radial margins with respect to the GTV and with 0.5-cm uniform margins for LN and LN(±). For the SMART plans, there were two planning target volumes (PTVs): PTV66 = (GTV + LN) + 0.5 cm and PTV54 = CTV + 0.5 cm. For the 3DCRT and cf-IMRT plans, there was only a single PTV: PTV60 = CTV + 0.5 cm. The prescribed dose for the SMART plans was 66 Gy/30 F to PTV66 and 54 Gy/30 F to PTV54. The dose prescription to the PTV60 for both the 3DCRT and cf-IMRT plans was set to 60 Gy/30 F. All the plans were generated on the Eclipse 10.0 treatment planning system. Fulfillment of the dose criteria for the PTVs received the highest priority, followed by the spinal cord, heart, and lungs. The dose-volume histograms were compared.
RESULTS: Clinically acceptable plans were achieved for all the SMART, cf-IMRT, and 3DCRT plans. Compared with the 3DCRT plans, the SMART plans increased the dose delivered to the primary tumor (66 Gy vs 60 Gy), with improved sparing of normal tissues in all patients. The Dmax of the spinal cord, V20 of the lungs, and Dmean and V50 of the heart for the SMART and 3DCRT plans were as follows: 38.5 ± 2.0 vs 44.7 ± 0.8 (P = 0.002), 17.1 ± 4.0 vs 25.8 ± 5.0 (P = 0.000), 14.4 ± 7.5 vs 21.4 ± 11.1 (P = 0.000), and 4.9 ± 3.4 vs 12.9 ± 7.6 (P = 0.000), respectively. In contrast to the cf-IMRT plans, the SMART plans permitted a simultaneous dose escalation (6 Gy) to the primary tumor while demonstrating a significant trend of a lower irradiation dose to all organs at risk except the spinal cord, for which no significant difference was found.
CONCLUSION: SMART offers the potential for a 6 Gy simultaneous escalation in the irradiation dose delivered to the primary tumor of EC and improves the sparing of normal tissues.
doi:10.3748/wjg.v20.i38.13973
PMCID: PMC4194581  PMID: 25320535
Simultaneous modulated accelerated radiation therapy; Three-dimensional conformal radiotherapy; Intensity-modulated radiation therapy; Esophageal cancer; Feasibility
8.  Is it beneficial to selectively boost high-risk tumor subvolumes? A comparison of selectively boosting high-risk tumor subvolumes versus homogeneous dose escalation of the entire tumor based on equivalent EUD plans 
Purpose
To quantify and compare expected local tumor control and expected normal tissue toxicities between selective boosting IMRT and homogeneous dose escalation IMRT for the case of prostate cancer.
Methods
Four different selective boosting scenarios and three different high-risk tumor subvolume geometries were designed to compare selective boosting and homogeneous dose escalation IMRT plans delivering the same equivalent uniform dose (EUD) to the entire PTV. For each scenario, differences in tumor control probability between both boosting strategies were calculated for the high-risk tumor subvolume and remaining lower-risk PTV, and were visualized using voxel based iso-TCP maps. Differences in expected rectal and bladder complications were quantified using radiobiological indices (generalized EUD (gEUD) and normal tissue complication probability (NTCP)) as well as %-volumes.
Results
For all investigated scenarios and high-risk tumor subvolume geometries, selective boosting IMRT improves expected TCP compared to homogeneous dose escalation IMRT, especially when lack of control of the high-risk tumor subvolume could be the cause for tumor recurrence. Employing, selective boosting IMRT significant increases in expected TCP can be achieved for the high-risk tumor subvolumes. The 3 conventional selective boosting IMRT strategies, employing physical dose objectives, did not show significant improvement in rectal and bladder sparing as compared to their counterpart homogeneous dose escalation plans. However, risk-adaptive optimization, utilizing radiobiological objective functions, resulted in reduction in NTCP for the rectum when compared to its corresponding homogeneous dose escalation plan.
Conclusions
Selective boosting is a more effective method than homogeneous dose escalation for achieving optimal treatment outcomes. Furthermore, risk-adaptive optimization increases the therapeutic ratio as compared to conventional selective boosting IMRT.
doi:10.1080/02841860701843050
PMCID: PMC2794432  PMID: 18568486
Functional imaging; selective boosting; dose painting; TCP; IMRT
9.  Comparison of Oncentra® Brachy IPSA and graphical optimisation techniques: a case study of HDR brachytherapy head and neck and prostate plans 
There are a number of different dwell positions and time optimisation options available in the Oncentra® Brachy (Elekta Brachytherapy Solutions, Veenendaal, The Netherlands) brachytherapy treatment planning system. The purpose of this case study was to compare graphical (GRO) and inverse planning by simulated annealing (IPSA) optimisation techniques for interstitial head and neck (HN) and prostate plans considering dosimetry, modelled radiobiology outcome and planning time. Four retrospective brachytherapy patients were chosen for this study, two recurrent HN and two prostatic boosts. Manual GRO and IPSA plans were generated for each patient. Plans were compared using dose–volume histograms (DVH) and dose coverage metrics including; conformity index (CI), homogeneity index (HI) and conformity number (CN). Logit and relative seriality models were used to calculate tumour control probability (TCP) and normal tissue complication probability (NTCP). Approximate planning time was also recorded. There was no significant difference between GRO and IPSA in terms of dose metrics with mean CI of 1.30 and 1.57 (P > 0.05) respectively. IPSA achieved an average HN TCP of 0.32 versus 0.12 for GRO while for prostate there was no significant difference. Mean GRO planning times were greater than 75 min while average IPSA planning times were less than 10 min. Planning times for IPSA were greatly reduced compared to GRO and plans were dosimetrically similar. For this reason, IPSA makes for a useful planning tool in HN and prostate brachytherapy.
doi:10.1002/jmrs.107
PMCID: PMC4462990
head and neck; IPSA; optimisation; prostate
10.  Comparison of dose distributions and organs at risk (OAR) doses in conventional tangential technique (CTT) and IMRT plans with different numbers of beam in left-sided breast cancer 
Aim
Our aim was to improve dose distribution to the left breast and to determine the dose received by the ipsilateral lung, heart, contralateral lung and contralateral breast during primary left-sided breast irradiation by using intensity modulated radiotherapy (IMRT) techniques compared to conventional tangential techniques (CTT). At the same time, different beams of IMRT plans were compared to each other in respect to CI, HI and organs at risk (OAR) dose.
Background
Conventional early breast cancer treatment consists of lumpectomy followed by whole breast radiation therapy. CTT is a traditional method used for whole breast radiotherapy and includes standard wedged tangents (two opposed wedged tangential photon beams). The IMRT technique has been widely used for many treatment sites, allowing both improved sparing of normal tissues and more conformal dose distributions. IMRT is a new technique for whole breast radiotherapy. IMRT is used to improve conformity and homogeneity and used to reduce OAR doses.
Materials and methods
Thirty patients with left-sided breast carcinoma were treated between 2005 and 2008 using 6, 18 or mixed 6/18 MV photons for primary breast irradiation following breast conserving surgery (BCS). The clinical target volume [CTV] was contoured as a target volume and the contralateral breast, ipsilateral lung, contralateral lung and heart tissues as organs at risk (OAR). IMRT with seven beams (IMRT7), nine beams (IMRT9) and 11 beams (IMRT11) plans were developed and compared with CTT and among each other. The conformity index (CI), homogeneity index (HI), and doses to OAR were compared to each other.
Results
All of IMRT plans significantly improved CI (CTT: 0.76; IMRT7: 0.84; IMRT9: 0.84; IMRT11: 0.85), HI (CTT: 1.16; IMRT7: 1.12; IMRT9: 1.11; IMRT11: 1.11), volume of the ipsilateral lung receiving more than 20 Gy (>V20 Gy) (CTT: 14.6; IMRT7: 9.08; IMRT9: 8.10; IMRT11: 8.60), and volume of the heart receiving more than 30 Gy (>V30 Gy) (CTT: 6.7; IMRT7: 4.04; IMRT9: 2.80; IMRT11: 2.98) compared to CTT. All IMRT plans were found to significantly decrease >V20 Gy and >V30 Gy volumes compared to conformal plans. But IMRT plans increased the volume of OAR receiving low dose radiotherapy: volume of contralateral lung receiving 5 and 10 Gy (CTT: 0.0–0.0; IMRT7: 19.0–0.7; IMRT9: 17.2–0.66; IMRT11: 18.7–0.58, respectively) and volume of contralateral breast receiving 10 Gy (CTT: 0.03; IMRT7: 0.38; IMRT9: 0.60; IMRT11: 0.68). The differences among IMRT plans with increased number of beams were not statistically significant.
Conclusion
IMRT significantly improved conformity and homogeneity index for plans. Heart and lung volumes receiving high doses were decreased, but OAR receiving low doses was increased.
doi:10.1016/j.rpor.2011.02.001
PMCID: PMC3863158  PMID: 24376964
Breast cancer; IMRT; Left breast; Whole breast radiotherapy; IMRT; Conventional techniques comparison
11.  Increase in Tumor Control and Normal Tissue Complication Probabilities in Advanced Head-and-Neck Cancer for Dose-Escalated Intensity-Modulated Photon and Proton Therapy 
Frontiers in Oncology  2015;5:256.
Introduction
Presently used radiochemotherapy regimens result in moderate local control rates for patients with advanced head-and-neck squamous cell carcinoma (HNSCC). Dose escalation (DE) may be an option to improve patient outcome, but may also increase the risk of toxicities in healthy tissue. The presented treatment planning study evaluated the feasibility of two DE levels for advanced HNSCC patients, planned with either intensity-modulated photon therapy (IMXT) or proton therapy (IMPT).
Materials and methods
For 45 HNSCC patients, IMXT and IMPT treatment plans were created including DE via a simultaneous integrated boost (SIB) in the high-risk volume, while maintaining standard fractionation with 2 Gy per fraction in the remaining target volume. Two DE levels for the SIB were compared: 2.3 and 2.6 Gy. Treatment plan evaluation included assessment of tumor control probabilities (TCP) and normal tissue complication probabilities (NTCP).
Results
An increase of approximately 10% in TCP was estimated between the DE levels. A pronounced high-dose rim surrounding the SIB volume was identified in IMXT treatment. Compared to IMPT, this extra dose slightly increased the TCP values and to a larger extent the NTCP values. For both modalities, the higher DE level led only to a small increase in NTCP values (mean differences <2%) in all models, except for the risk of aspiration, which increased on average by 8 and 6% with IMXT and IMPT, respectively, but showed a considerable patient dependence.
Conclusion
Both DE levels appear applicable to patients with IMXT and IMPT since all calculated NTCP values, except for one, increased only little for the higher DE level. The estimated TCP increase is of relevant magnitude. The higher DE schedule needs to be investigated carefully in the setting of a prospective clinical trial, especially regarding toxicities caused by high local doses that lack a sound dose–response description, e.g., ulcers.
doi:10.3389/fonc.2015.00256
PMCID: PMC4653282  PMID: 26636038
photon radiotherapy; proton radiotherapy; tumor control probability; normal tissue complication probability; head-and-neck cancer
12.  Volumetric-modulated arc therapy vs c-IMRT in esophageal cancer: A treatment planning comparison 
AIM: To compare the volumetric-modulated arc therapy (VMAT) plans with conventional sliding window intensity-modulated radiotherapy (c-IMRT) plans in esophageal cancer (EC).
METHODS: Twenty patients with EC were selected, including 5 cases located in the cervical, the upper, the middle and the lower thorax, respectively. Five plans were generated with the eclipse planning system: three using c-IMRT with 5 fields (5F), 7 fields (7F) and 9 fields (9F), and two using VMAT with a single arc (1A) and double arcs (2A). The treatment plans were designed to deliver a dose of 60 Gy to the planning target volume (PTV) with the same constrains in a 2.0 Gy daily fraction, 5 d a week. Plans were normalized to 95% of the PTV that received 100% of the prescribed dose. We examined the dose-volume histogram parameters of PTV and the organs at risk (OAR) such as lungs, spinal cord and heart. Monitor units (MU) and normal tissue complication probability (NTCP) of OAR were also reported.
RESULTS: Both c-IMRT and VMAT plans resulted in abundant dose coverage of PTV for EC of different locations. The dose conformity to PTV was improved as the number of field in c-IMRT or rotating arc in VMAT was increased. The doses to PTV and OAR in VMAT plans were not statistically different in comparison with c-IMRT plans, with the following exceptions: in cervical and upper thoracic EC, the conformity index (CI) was higher in VMAT (1A 0.78 and 2A 0.8) than in c-IMRT (5F 0.62, 7F 0.66 and 9F 0.73) and homogeneity was slightly better in c-IMRT (7F 1.09 and 9F 1.07) than in VMAT (1A 1.1 and 2A 1.09). Lung V30 was lower in VMAT (1A 12.52 and 2A 12.29) than in c-IMRT (7F 14.35 and 9F 14.81). The humeral head doses were significantly increased in VMAT as against c-IMRT. In the middle and lower thoracic EC, CI in VMAT (1A 0.76 and 2A 0.74) was higher than in c-IMRT (5F 0.63 Gy and 7F 0.67 Gy), and homogeneity was almost similar between VMAT and c-IMRT. V20 (2A 21.49 Gy vs 7F 24.59 Gy and 9F 24.16 Gy) and V30 (2A 9.73 Gy vs 5F 12.61 Gy, 7F 11.5 Gy and 9F 11.37 Gy) of lungs in VMAT were lower than in c-IMRT, but low doses to lungs (V5 and V10) were increased. V30 (1A 48.12 Gy vs 5F 59.2 Gy, 7F 58.59 Gy and 9F 57.2 Gy), V40 and V50 of heart in VMAT was lower than in c-IMRT. MUs in VMAT plans were significantly reduced in comparison with c-IMRT, maximum doses to the spinal cord and mean doses of lungs were similar between the two techniques. NTCP of spinal cord was 0 for all cases. NTCP of lungs and heart in VMAT were lower than in c-IMRT. The advantage of VMAT plan was enhanced by doubling the arc.
CONCLUSION: Compared with c-IMRT, VMAT, especially the 2A, slightly improves the OAR dose sparing, such as lungs and heart, and reduces NTCP and MU with a better PTV coverage.
doi:10.3748/wjg.v18.i37.5266
PMCID: PMC3468860  PMID: 23066322
Esophageal cancer; Treatment planning; Intensity modulated radiotherapy; Volumetric modulated arc radiotherapy; Normal tissue complication probability
13.  An assessment of PTV margin based on actual accumulated dose for prostate cancer radiotherapy 
Physics in medicine and biology  2013;58(21):7733-7744.
The purpose of this work is to present the results of a margin reduction study involving dosimetric and radiobiologic assessment of cumulative dose distributions, computed using an image guided adaptive radiotherapy based framework. Eight prostate cancer patients, treated with 7–9, 6 MV, intensity modulated radiation therapy (IMRT) fields, were included in this study. The workflow consists of cone beam CT (CBCT) based localization, deformable image registration of the CBCT to simulation CT image datasets (SIMCT), dose reconstruction and dose accumulation on the SIM-CT, and plan evaluation using radiobiological models. For each patient, three IMRT plans were generated with different margins applied to the CTV. The PTV margin for the original plan was 10 mm and 6 mm at the prostate/anterior rectal wall interface (10/6 mm) and was reduced to: (a) 5/3 mm, and (b) 3 mm uniformly. The average percent reductions in predicted tumor control probability (TCP) in the accumulated (actual) plans in comparison to the original plans over eight patients were 0.4%, 0.7% and 11.0% with 10/6 mm, 5/3 mm and 3 mm uniform margin respectively. The mean increase in predicted normal tissue complication probability (NTCP) for grades 2/3 rectal bleeding for the actual plans in comparison to the static plans with margins of 10/6, 5/3 and 3 mm uniformly was 3.5%, 2.8% and 2.4% respectively. For the actual dose distributions, predicted NTCP for late rectal bleeding was reduced by 3.6% on average when the margin was reduced from 10/6 mm to 5/3 mm, and further reduced by 1.0% on average when the margin was reduced to 3 mm. The average reduction in complication free tumor control probability (P+) in the actual plans in comparison to the original plans with margins of 10/6, 5/3 and 3 mm was 3.7%, 2.4% and 13.6% correspondingly. The significant reduction of TCP and P+ in the actual plan with 3 mm margin came from one outlier, where individualizing patient treatment plans through margin adaptation based on biological models, might yield higher quality treatments.
doi:10.1088/0031-9155/58/21/7733
PMCID: PMC4073000  PMID: 24140847
14.  Image-guided radiotherapy of the prostate using daily CBCT: the feasibility and likely benefit of implementing a margin reduction 
The British Journal of Radiology  2014;87(1044):20140459.
Objective:
To investigate whether planning target volume (PTV) margins may be safely reduced in radiotherapy of localized prostate cancer incorporating daily online tube potential-cone beam CT (CBCT) image guidance and the anticipated benefit in predicted rectal toxicity.
Methods:
The prostate-only clinical target volume (CTV2) and rectum were delineated on 1 pre-treatment CBCT each week in 18 randomly selected patients. By transposing these contours onto the original plan, dose–volume histograms (DVHs) for CTV2 and the rectum were each calculated and combined, for each patient, to produce a single mean DVH representative of the dose delivered over the treatment course. Plans were reoptimized using reduced CTV2 to PTV2 margins and the consequent radiobiological impact modelled by the tumour control probability (TCP) and normal tissue complication probability (NTCP) of the rectum.
Results:
All CBCT images were deemed of sufficient quality to identify the CTV and rectum. No loss of TCP was observed when plans using the standard 5-mm CTV2 to PTV2 margin of the centre were reoptimized with a 4- or 3-mm margin. Margin reduction was associated with a significant decrease in rectal NTCP (5–4 mm; p < 0.05 and 5–3 mm; p < 0.01).
Conclusion:
Using daily online image guidance with CBCT, a reduction in CTV2 to PTV2 margins to 3 mm is achievable without compromising tumour control. The consequent sparing of surrounding normal tissues is associated with reduced anticipated rectal toxicity.
Advances in knowledge:
Margin reduction is feasible and potentially beneficial. Centres with image-guided radiotherapy capability should consider assessing whether margin reduction is possible within their institutes.
doi:10.1259/bjr.20140459
PMCID: PMC4243197  PMID: 25354015
15.  A study on conventional IMRT and RapidArc treatment planning techniques for head and neck cancers 
Aim
To evaluate the performance of volumetric arc modulation with RapidArc against conventional IMRT for head and neck cancers.
Background
RapidArc is a novel technique that has recently been made available for clinical use. Planning study was done for volumetric arc modulation with RapidArc against conventional IMRT for head and neck cancers.
Materials and methods
Ten patients with advanced tumors of the nasopharynx, oropharynx, and hypopharynx were selected for the planning comparison study. PTV was delineated for two different dose levels and planning was done by means of simultaneously integrated boost technique. A total dose of 70 Gy was delivered to the boost volume (PTV boost) and 57.7 Gy to the elective PTV (PTV elective) in 35 equal treatment fractions. PTV boost consisted of the gross tumor volume and lymph nodes containing visible macroscopic tumor or biopsy-proven positive lymph nodes, whereas the PTV elective consisted of elective nodal regions. Planning was done for IMRT using 9 fields and RapidArc with single arc, double arc. Beam was equally placed for IMRT plans. Single arc RapidArc plan utilizes full 360° gantry rotation and double arc consists of 2 co-planar arcs of 360° in clockwise and counter clockwise direction. Collimator was rotated from 35 to 45° to cover the entire tumor, which reduced the tongue and groove effect during gantry rotation. All plans were generated with 6 MV X-rays for CLINAC 2100 Linear Accelerator. Calculations were done in the Eclipse treatment planning system (version 8.6) using the AAA algorithm.
Results
Double arc plans show superior dose homogeneity in PTV compared to a single arc and IMRT 9 field technique. Target coverage was almost similar in all the techniques. The sparing of spinal cord in terms of the maximum dose was better in the double arc technique by 4.5% when compared to the IMRT 9 field and single arc techniques. For healthy tissue, no significant changes were observed between the plans in terms of the mean dose and integral dose. But RapidArc plans showed a reduction in the volume of the healthy tissue irradiated at V15 Gy (5.81% for single arc and 4.69% for double arc) and V20 Gy (7.55% for single arc and 5.89% for double arc) dose levels when compared to the 9-Field IMRT technique. For brain stem, maximum dose was similar in all the techniques. The average MU (±SD) needed to deliver the dose of 200 cGy per fraction was 474 ± 80 MU and 447 ± 45 MU for double arc and single arc as against 948 ± 162 MU for the 9-Field IMRT plan. A considerable reduction in maximum dose to the mandible by 6.05% was observed with double arc plan. Double arc shows a reduction in the parotid mean dose when compared with single arc and IMRT plans.
Conclusion
RapidArc using double arc provided a significant sparing of OARs and healthy tissue without compromising target coverage compared to IMRT. The main disadvantage with IMRT observed was higher monitor units and longer treatment time.
doi:10.1016/j.rpor.2012.01.009
PMCID: PMC3863199  PMID: 24377020
RapidArc; IMRT; Planning study; Head and neck cancers
16.  Preliminary comp arison of helical tomotherapy and mixed beams of unmodulated electrons and intensity modulated radiation therapy for treating superficial cancers of the parotid gland and nasal cavity 
Background and Purpose
To investigate combining unmodulated electron beams with intensity-modulated radiation therapy to improve dose distributions for superficial head and neck cancers, and to compare mixed beam plans with helical tomotherapy.
Materials and methods
Mixed beam and helical tomotherapy dose plans were developed for two patients with parotid gland tumors and two patients with nasal cavity tumors. Mixed beam plans consisted of various weightings of a enface electron beam and IMRT, which was optimized after calculation of the electron dose to compensate for heterogeneity in the electron dose distribution within the target volume.
Results
Helical tomotherapy plans showed dose conformity and homogeneity in the target volume that was equal to or better than the mixed beam plans. Electron-only plans tended to show the lowest doses to normal tissues, but with markedly worse dose conformity and homogeneity than in the other plans. However, adding a 20% IMRT dose fraction (i.e., IMRT:electron weighting = 1:4) to the electron plan restored target conformity and homogeneity to values comparable to helical tomotherapy plans, while maintaining lower normal tissue dose.
Conclusions
Mixed beam treatments offer some dosimetric advantages over IMRT or helical tomotherapy for target depths that do not exceed the useful range of the electron beam. Adding a small IMRT component (e.g., IMRT:electron weighting = 1:4) to electron beam plans markedly improved target dose homogeneity and conformity for the cases examined in this study.
doi:10.1186/1748-717X-6-178
PMCID: PMC3274488  PMID: 22204477
electron beam therapy; intensity modulated radiation therapy; helical tomotherapy; mixed beam therapy; head and neck cancer
17.  Dosimetric comparison of intensity modulated radiotherapy isocentric field plans and field in field (FIF) forward plans in the treatment of breast cancer 
The present study is aimed at comparing the planning and delivery efficiency between three-dimensional conformal radiotherapy (3D-CRT), field-in-field, forward planned, intensity modulated radiotherapy (FIF-FP-IMRT), and inverse planned intensity modulated radiotherapy (IP-IMRT). Treatment plans of 20 patients with left-sided breast cancer, 10 post-mastectomy treated to a prescribed dose of 45 Gy to the chest wall in 20 fractions, and 10 post-breast-conserving surgery to a prescribed dose of 50 Gy to the whole breast in 25 fractions, with 3D-CRT were selected. The FiF-FP-IMRT plans were created by combining two open fields with three to four segments in two tangential beam directions. Eight different beam directions were chosen to create IP-IMRT plans and were inversely optimized. The homogeneity of dose to planning target volume (PTV) and the dose delivered to heart and contralateral breast were compared among the techniques in all the 20 patients. All the three radiotherapy techniques achieved comparable radiation dose delivery to PTV-95% of the prescribed dose covering > 95% of the breast PTV. The mean volume of PTV receiving 105% (V105) of the prescribed dose was 1.7% (range 0-6.8%) for IP-IMRT, 1.9% for FP-IMRT, and 3.7% for 3D-CRT. The homogeneity and conformity indices (HI and CI) were similar for 3D-CRT and FP-IMRT, whereas the IP-IMRT plans had better conformity index at the cost of less homogeneity. The 3D-CRT and FiF-FP-IMRT plans achieved similar sparing of critical organs. The low-dose volumes (V5Gy) in the heart and lungs were larger in IP-IMRT than in the other techniques. The value of the mean dose to the ipsilateral lung was higher for IP-IMRT than the values for with FiF-FP-IMRT and 3D-CRT. In the current study, the relative volume of contralateral breast receiving low doses (0.01, 0.6, 1, and 2Gy) was significantly lower for the FiF-FP-IMRT and 3D-CRT plans than for the IP-IMRT plan. Compared with 3D-CRT and IP-IMRT, FiF-FP-IMRT proved to be a simple and efficient planning technique for breast irradiation. It provided dosimetric advantages, significantly reducing the size of the hot spot and minimally improving the coverage of the target volume. In addition, it was felt that FiF-FP-IMRT required less planning time and easy field placements.
doi:10.4103/0971-6203.106601
PMCID: PMC3607341  PMID: 23531607
Breast cancer; contralateral breast; field in field breast plan; intensity-modulated radiation therapy
18.  Dose verification of helical tomotherapy intensity modulated radiation therapy planning using 2D-array ion chambers 
Xu, S | Xie, C | Ju, Z | Dai, X | Gong, H | Wang, L | Yang, J
Purpose:
To investigate the clinical usage of dose verification of Helical Tomotherapy plans by using 2D-array ion chambers, and to develop an efficient way to validate the dose delivered for the patients during treatments.
Materials and Methods:
A pixel-segmented ionisation chamber device, IMRT MatriXX™ and Multicube™ phantom from IBA were used on ten selected Tomotherapy IMRT/IGRT head and neck plans in this study. The combined phantom was set up to measure the dose distribution from coronal and sagittal planes. The setup of phantom was guided for verifying the correction position by pre-treatment Tomotherapy MVCT images. After the irradiation, the measured dose distributions of coronal and sagittal planes were compared with those from calculation by the planning system for cross verification. The results were evaluated by the absolute and relative doses as well as Gamma (γ) function. The feasibility of the different measuring methods was studied for this rotational treatment technique.
Results:
The dose distributions measured by the MatriXX 2D array were in good agreements with plans calculated by Tomotherapy planning system. The discrepancy between the measured dose and predicted dose in the selected points was within ±3%. In the comparison of the pixel-segmented ionisation chamber versus treatment planning system using the 3 mm/3% γ-function criteria, the mean passing rates of 2 mm dose grid with γ-parameter ≤1 were 97.37% and 96.91%, in two orthogonal planes (coronal and sagittal directions), respectively.
Conclusion:
MatriXX with Multicube is a new system created for rotational delivery quality assurance (QA) and found to be reliable to measure both absolute dose and relative dose distributions, simultaneously. It achieves the goal of an efficient and accurate dosimetry validation method of the helical delivery pattern for the Helical Tomotherapy IMRT planning.
doi:10.2349/biij.6.2.e24
PMCID: PMC3097769  PMID: 21611040
Tomotherapy; dose verification; IMRT; radiation therapy; QA
19.  P13.25A RADIOBIOLOGICAL COMPARISON BETWEEN THE INVERSE INTENSITY MODULATED RADIATION THERAPY AND THE FIELD IN FIELD INTENSITY MODULATED RADIATION THERAPY FOR THE TREATMENT OF GLIOBLASTOMA 
Neuro-Oncology  2014;16(Suppl 2):ii71.
For critical structures the use of maximum or mean dose limits in the intensity modulated radiation therapy (IMRT) optimization is not very meaningful. The dose-volume limits and equivalent uniform dose (EUD) which is defined as the uniform dose that would lead to the same effect as the given non-uniform dose in as particular organ are combined to analyze the volume effect. The normal tissue complication probability (NTCP) is a predictor of radiobiological effect for organs at risk (OAR). The calculation of the NTCP is based on the DVH which is generated by the treatment planning system after calculation of the 3D dose distribution. Uniform EUD irradiation of an OAR results in the same NTCP as the original non-homogeneous distribution. The NTCP equation is therefore represented as a function of EUD. The inverse equation expresses EUD as a function of NTCP. Expressing NTCP in terms of EUD represents a step toward simplifying the conceptual framework for modeling probability of expected complications. The aim of this study is to compare radiobiological effects between the fif IMRT and inverse IMRT for treatment of Glioblastoma (GBM) using the equivalent uniform dose (EUD) and normal tissue complication probability (NTCP). Five representative patients treated with definitive radiation using IMRT at our clinic in the last two year were selected for treatment planning study. Criteria for inclusion were glioblastoma . The normal tissues (Organ at Risk, OaR) contoured included brain-stem, optic chiasm, optic nerves, right-left cohclea and whole brain. Brain was defined as total brain tissue minus the PTV. Two different radiation therapy techniques; inverse IMRT and FiF IMRT treatment plans were optimised with the prescription dose 60 Gy/30 fractions. All those calculations and IMRT optimizations were performed using the Prowess Panther DAQ TPS with 6 MV,Siemens Artiste, MLC with 160 leaves and evaluated by using EUD and NTCP models. In the present study, target dose coverage was improved with inverse IMRT planning as compared with fif IMRT planning. With respect to NTCP there is no significant differences between fif IMRT planning and inverse IMRT planning. For the optic chiasm, brainstem, right-left eyes and right-left lens the NTCP values were calculated to be smaller than %1 for both IMRT plannings, except for GBM3 patient as a result of eye(L) concurrent with PTV. So the maximum NTCP was 1 for lens(L) of GBM3 patient for both plannings. Eye(L) of NTCP values were 0.15479 and 0.10896 respectively for this patient with a frontosfenoidal tumor and a biggest size of tumor, 8.82 cm. After obtaining these results we decided to compare also the total monitor units (MU) of optimizations. Then, we find that total MU value of the fif IMRT plannings are smaller than inverse IMRT plannings. So, the fif IMRT planning can be chosen for short treatment time and comfort of the patients for GBM patients treatment.
doi:10.1093/neuonc/nou174.271
PMCID: PMC4185629
20.  Comparison of the helical tomotherapy against the multileaf collimator-based intensity-modulated radiotherapy and 3D conformal radiation modalities in lung cancer radiotherapy 
The British Journal of Radiology  2011;84(998):161-172.
Objectives
The aim of this study was to compare three-dimensional (3D) conformal radiotherapy and the two different forms of IMRT in lung cancer radiotherapy.
Methods
Cases of four lung cancer patients were investigated by developing a 3D conformal treatment plan, a linac MLC-based step-and-shoot IMRT plan and an HT plan for each case. With the use of the complication-free tumour control probability (P+) index and the uniform dose concept as the common prescription point of the plans, the different treatment plans were compared based on radiobiological measures.
Results
The applied plan evaluation method shows the MLC-based IMRT and the HT treatment plans are almost equivalent over the clinically useful dose prescription range; however, the 3D conformal plan inferior. At the optimal dose levels, the 3D conformal treatment plans give an average P+ of 48.1% for a effective uniform dose to the internal target volume (ITV) of 62.4 Gy, whereas the corresponding MLC-based IMRT treatment plans are more effective by an average ΔP+ of 27.0% for a Δ effective uniform dose of 16.3 Gy. Similarly, the HT treatment plans are more effective than the 3D-conformal plans by an average ΔP+ of 23.8% for a Δ effective uniform dose of 11.6 Gy.
Conclusion
A radiobiological treatment plan evaluation can provide a closer association of the delivered treatment with the clinical outcome by taking into account the dose–response relations of the irradiated tumours and normal tissues. The use of P – effective uniform dose diagrams can complement the traditional tools of evaluation to compare and effectively evaluate different treatment plans.
doi:10.1259/bjr/89275085
PMCID: PMC3473851  PMID: 20858664
21.  Brain-Sparing Methods for IMRT of Head and Neck Cancer 
PLoS ONE  2015;10(3):e0120141.
Purpose
Radical radiotherapy for head and neck cancer (HNC) may deliver significant doses to brain structures. There is evidence that this may cause a decline in neurocognitive function (NCF). Radiation dose to the medial temporal lobes, and particularly to the hippocampi, seems to be critical in determining NCF outcomes. We evaluated the feasibility of two alternative intensity-modulated radiotherapy (IMRT) techniques to generate hippocampus- and brain-sparing HNC treatment plans to preserve NCF.
Methods and Materials
A planning study was undertaken for ten patients with HNC whose planning target volume (PTV) included the nasopharynx. Patients had been previously treated using standard (chemo)-IMRT techniques. Bilateral hippocampi were delineated according to the RTOG atlas, on T1w MRI co-registered to the RT planning CT. Hippocampus-sparing plans (HSRT), and whole-brain/hippocampus-sparing fixed-field non-coplanar IMRT (BSRT) plans, were generated. DVHs and dose difference maps were used to compare plans. NTCP calculations for NCF impairment, based on hippocampal dosimetry, were performed for all plans.
Results
Significant reductions in hippocampal doses relative to standard plans were achieved in eight of ten cases for both HSRT and BSRT. EQD2 D40% to bilateral hippocampi was significantly reduced from a mean of 23.5 Gy (range 14.5–35.0) in the standard plans to a mean of 8.6 Gy (4.2–24.7) for HSRT (p = 0.001) and a mean of 9.0 Gy (4.3–17.3) for BSRT (p < 0.001). Both HSRT and BSRT resulted in a significant reduction in doses to the whole brain, brain stem, and cerebellum.
Conclusion
We demonstrate that IMRT plans for HNC involving the nasopharynx can be successfully optimised to significantly reduce dose to the bilateral hippocampi and whole brain. The magnitude of the achievable dose reductions results in significant reductions in the probability of radiation-induced NCF decline. These results could readily be translated into a future clinical trial.
doi:10.1371/journal.pone.0120141
PMCID: PMC4364536  PMID: 25781636
22.  Exploiting biological and physical determinants of radiotherapy toxicity to individualize treatment 
The British Journal of Radiology  2015;88(1051):20150172.
The recent advances in radiation delivery can improve tumour control probability (TCP) and reduce treatment-related toxicity. The use of intensity-modulated radiotherapy (IMRT) in particular can reduce normal tissue toxicity, an objective in its own right, and can allow safe dose escalation in selected cases. Ideally, IMRT should be combined with image guidance to verify the position of the target, since patients, target and organs at risk can move day to day. Daily image guidance scans can be used to identify the position of normal tissue structures and potentially to compute the daily delivered dose. Fundamentally, it is still the tolerance of the normal tissues that limits radiotherapy (RT) dose and therefore tumour control. However, the dose–response relationships for both tumour and normal tissues are relatively steep, meaning that small dose differences can translate into clinically relevant improvements. Differences exist between individuals in the severity of toxicity experienced for a given dose of RT. Some of this difference may be the result of differences between the planned dose and the accumulated dose (DA). However, some may be owing to intrinsic differences in radiosensitivity of the normal tissues between individuals. This field has been developing rapidly, with the demonstration of definite associations between genetic polymorphisms and variation in toxicity recently described. It might be possible to identify more resistant patients who would be suitable for dose escalation, as well as more sensitive patients for whom toxicity could be reduced or avoided. Daily differences in delivered dose have been investigated within the VoxTox research programme, using the rectum as an example organ at risk. In patients with prostate cancer receiving curative RT, considerable daily variation in rectal position and dose can be demonstrated, although the median position matches the planning scan well. Overall, in 10 patients, the mean difference between planned and accumulated rectal equivalent uniform doses was −2.7 Gy (5%), and a dose reduction was seen in 7 of the 10 cases. If dose escalation was performed to take rectal dose back to the planned level, this should increase the mean TCP (as biochemical progression-free survival) by 5%. Combining radiogenomics with individual estimates of DA might identify almost half of patients undergoing radical RT who might benefit from either dose escalation, suggesting improved tumour cure or reduced toxicity or both.
doi:10.1259/bjr.20150172
PMCID: PMC4628540  PMID: 26084351
23.  P13.15USING IMAGE-GUIDED AND INTENSITY-MODULATED RADIOTHERAPY TO REDUCE SCALP DOSE AND RADIOTHERAPY-RELATED ALOPECIA FOR PATIENTS WITH INTRACRANIAL TUMOURS TREATED WITH TOMOTHERAPY 
Neuro-Oncology  2014;16(Suppl 2):ii69.
INTRODUCTION: Radiotherapy to intracranial tumours commonly results in permanent alopecia on the scalp, an important and distressing side-effect that has a negative impact on patient quality-of-life. We demonstrated that the radiotherapy dose to the scalp can be examined during radiotherapy planning and can be reduced by the adoption of image-guided and intensity-modulated radiotherapy techniques. METHOD: Twelve patients were selected who had been treated using TomoTherapy at Cambridge University Hospitals and had suffered resulting alopecia. A method of producing a realistic ‘hair-bearing scalp’ structure in the radiotherapy planning software was developed to record scalp dosimetry. Image-guided radiotherapy (IGRT) systems such as TomoTherapy enable correction of patient setup errors and can facilitate the reduction of radiotherapy planning margins. We produced new treatment plans for the 12 patients using both 5mm and 3mm CTV-PTV margins to examine the changes in scalp dose that would result. A standardised inverse-planning optimisation protocol was used for each plan with fixed priorities, penalties and iterations. We also investigated the use of the hair-bearing scalp structure by the IMRT inverse-planning software as an avoid structure. In-vivo TLD measurements were carried out for a separate cohort of three patients to examine the correlation between planning system dose and delivered dose to the patient surface. RESULTS: We were able to produce detailed DVH data for the ‘hair-bearing scalp’ structure and show that the dose to the scalp was reduced significantly when 3mm rather than 5mm CTV-PTV margins were used. The mean scalp dose was reduced on average by 8.7% (p<0.0001). The V42.9Gy, the volume of scalp at 50% or higher risk of permanent alopecia (TD50), was reduced on average by 20.3% (p = 0.0008). Use of the scalp as an avoid structure reduced mean dose by 8.0% and V42.9Gy by 18.8%. There was excellent correlation between planned and in-vivo measured surface dose (correlation coefficient 0.96). CONCLUSIONS: Outlining the scalp hair field enables personalised prediction of the risk of permanent alopecia. Use of smaller CTV-PTV margins leads to significant reductions in scalp dose. Use of the scalp as a planning ‘avoid’ structure also may reduce dose to the scalp hair field. Alone or together these interventions may reduce the risk or extent of permanent alopecia. The TomoTherapy treatment planning system calculates skin doses accurately.
doi:10.1093/neuonc/nou174.261
PMCID: PMC4185618
24.  A dosimetric comparison of four treatment planning methods for high grade glioma 
Background
High grade gliomas (HGG) are typically treated with a combination of surgery, radiotherapy and chemotherapy. Three dimensional (3D) conformal radiotherapy treatment planning is still the main stay of treatment for these patients. New treatment planning methods suggest better dose distributions and organ sparing but their clinical benefit is unclear. The purpose of the current study was to compare normal tissue sparing and tumor coverage using four different radiotherapy planning methods in patients with high grade glioma.
Methods
Three dimensional conformal (3D), sequential boost IMRT, integrated boost (IB) IMRT and Tomotherapy (TOMO) treatment plans were generated for 20 high grade glioma patients. T1 and T2 MRI abnormalities were used to define GTV and CTV with 2 and 2.5 cm margins to define PTV1 and PTV2 respectively.
Results
The mean dose to PTV2 but not to PTV1 was less then 95% of the prescribed dose with IB and IMRT plans. The mean doses to the optic chiasm and the ipsilateral globe were highest with 3D plans and least with IB plans. The mean dose to the contralateral globe was highest with TOMO plans. The mean of the integral dose (ID) to the brain was least with the IB plan and was lower with IMRT compared to 3D plans. The TOMO plans had the least mean D10 to the normal brain but higher mean D50 and D90 compared to IB and IMRT plans. The mean D10 and D50 but not D90 were significantly lower with the IMRT plans compared to the 3D plans.
Conclusion
No single treatment planning method was found to be superior to all others and a personalized approach is advised for planning and treating high-grade glioma patients with radiotherapy. Integral dose did not reflect accurately the dose volume histogram (DVH) of the normal brain and may not be a good indicator of delayed radiation toxicity.
doi:10.1186/1748-717X-4-45
PMCID: PMC2774332  PMID: 19845946
25.  A comparative planning study of step-and-shoot IMRT versus helical tomotherapy for whole-pelvis irradiation in cervical cancer 
Journal of Radiation Research  2015;56(3):539-545.
The aim of this study was to compare the dosimetric parameters of whole-pelvis radiotherapy (WPRT) for cervical cancer between step-and-shoot IMRT (SaS-IMRT) and Helical Tomotherapy™ (HT). Retrospective analysis was performed on 20 cervical cancer patients who received WPRT in our center between January 2011 and January 2014. SaS-IMRT and HT treatment plans were generated for each patient. The dosimetric values for target coverage and organ-at-risk (OAR) sparing were compared according to the criteria of the International Commission on Radiation Units and Measurements 83 (ICRU 83) guidelines. Differences in beam-on time (BOT) were also compared. All the PTV dosimetric parameters (D5%, D50% and D95%) for the HT plan were (statistically significantly) of better quality than those for the SaS-IMRT plan (P-value < 0.001 in all respects). HT was also significantly more accurate than SaS-IMRT with respect to the D98% and Dmean of the CTV (P-values of 0.008 and <0.001, respectively). The median Conformity Index (CI) did not differ between the two plans (P-value = 0.057). However, the Uniformity Index for HT was significantly better than that for SaS-IMRT (P-value < 0.001). The median of D50% for the bladder, rectum and small bowel were significantly lower in HT planning than SaS-IMRT (P-value < 0.001). For D2%, we found that HT provided better sparing to the rectum and bladder (P-value < 0.001). However, the median of D2% for the small bowel was comparable for both plans. The median of Dmax of the head of the left femur was significantly lower in the HT plan, but this did not apply for the head of the right femur. BOT for HT was significantly shorter than for SaS-IMRT (P-value < 0.001). HT provided highly accurate plans, with more homogeneous PTV coverage and superior sparing of OARs than SaS-IMRT. In addition, HT enabled a shorter delivery time than SaS-IMRT.
doi:10.1093/jrr/rrv004
PMCID: PMC4426928  PMID: 25720771
IMRT; step-and-shoot; tomotherapy; cervical cancer

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