Simultaneously modulated accelerated radiation therapy reduces severe oesophageal toxicity in concomitant chemoradiotherapy of locally advanced non-small-cell lung cancer

Objective:

The aim of this study was to evaluate the potential of simultaneously modulated accelerated radiation therapy (SMART) to reduce the incidence of severe acute oesophagitis in the treatment of unresectable locally advanced non-small-cell lung cancer (LANSCLC).

Methods:

21 patients were treated with SMART and concomitant platinum-based chemotherapy. The prescribed doses were limited to 54 Gy at 1.8 Gy per day to the zones of presumed microscopic extent while simultaneously maintaining doses of 66 Gy at 2.2 Gy per day to the macroscopic disease. The whole treatment was delivered over 30 fractions and 6 weeks. Dosimetric parameters of SMART and the standard technique of irradiation [intensity-modulated radiation therapy (IMRT)] were compared. Acute toxicity was prospectively recorded.

Results:

The highest grade of oesophagitis was 62% (13 patients) grade 1, 33% (7 patients) grade 2 and 5% (1 patient) grade 3. Three (14%) patients experienced acute grade 2 pneumonitis. There was no grade 4 oesophageal or pulmonary toxicity. Doses to the organs at risk were significantly reduced in SMART compared with IMRT [oesophagus: V_50Gy, 28.5 Gy vs 39.9 Gy (p = 0.003); V_60Gy, 7.1 Gy vs 30.7 Gy (p = 0.003); lung: V_20Gy, 27.4 Gy vs 30.1 Gy (p = 0,002); heart: V_40Gy, 7.3 Gy vs 10.7 Gy (p = 0.006); spine: D_max, 42.4 Gy vs 46.4 Gy (p = 0.003)]. With a median follow-up of 18 months (6–33 months), the 1-year local control rate was 70% and the disease-free survival rate was 47%.

Conclusion:

SMART reduces the incidence of severe oesophagitis and improves the whole dosimetric predictors of toxicity for the lung, heart and spine.

Advances in knowledge:

Our study shows that SMART optimizes the therapeutic ratio in the treatment of LANSCLC, opening a window for dose intensification.     

Evaluation of hippocampus dose for patients undergoing intensity-modulated radiotherapy for nasopharyngeal carcinoma

Objective:

To evaluate the dose received by the hippocampus among patients undergoing intensity-modulated radiotherapy (IMRT) for nasopharyngeal cancer.

Methods:

10 patients with biopsy-proven, locally advanced nasopharyngeal cancer constituted the study population. The total prescribed dose to the planning target volume (PTV) was 70 Gy (D95%) delivered in 2.12-Gy daily fractions using IMRT. Using established anatomical guidelines, MRI co-registration and the assistance of a board-certified neuroradiologist, the right and left hippocampi were delineated on axial imaging from the CT scan obtained at simulation for each patient beginning at the most anterior portion of the lateral ventricle. IMRT treatment plans were generated without dose–volume constraints to the hippocampus. A range of dose–volume statistics was calculated.

Results:

The mean hippocampus volume was 6.01 ± 2.61 cm³. The mean V20 was 72.2%; V40 was 22.0%; V50 was 10.2%; and V60 was 5.5%. The average mean, minimum and maximum hippocampus doses were 30.27 Gy (range, 19.08–47.99 Gy); 17.54 Gy (range, 11.66–33.17 Gy); and 54.95 Gy (range, 35.59–75.57 Gy), respectively. The hippocampus received a maximum dose exceeding 70 Gy in 30% of cases.

Conclusion:

Our dosimetric analysis suggests that, for patients undergoing IMRT for nasopharyngeal cancer, the hippocampus routinely receives significantly high doses.

Advances in knowledge:

The hippocampus receives a fair amount of incidental radiation during treatment for nasopharyngeal cancer. Given the importance of this structure with respect to memory and neurocognitive function, consideration should be given to identifying the hippocampus as a critical organ at risk in the IMRT optimization process.Although intensity-modulated radiotherapy (IMRT) has supplanted two-dimensional and three-dimensional radiotherapies as the standard treatment for patients with head and neck cancer, it has become increasingly clear that the generation of highly conformal plans with steep fall-off gradients may come at the expense of significant doses to non-delineated extra-target organs.¹ Owing to the anatomical proximity of many head and neck cancers to the central nervous system, studies investigating the effects of radiation exposure on specific structures in the brain responsible for neurocognitive functioning may be warranted.Located within the temporal lobes, the hippocampus is a horseshoe-shaped paired structure that is a critical component of the limbic system. Its functions relate to the formation of new memories, spatial navigation and the connection of emotions and senses, such as smell and sound, to memories. Although the tolerance of this structure to radiation has yet to be fully established, it has been hypothesized that incidental exposure to this structure may contribute to both short-term toxicity, such as lack of inhibition and disequilibrium, as well as long-term memory loss.² Thus, the purpose of this study was to conduct a dosimetric analysis in patients with nasopharyngeal cancer treated by IMRT to assess incidental exposure to the hippocampus.     

Stereotactic body radiation therapy for a new lung cancer arising after pneumonectomy: dosimetric evaluation and pulmonary toxicity

Objective:

To evaluate the tolerance of stereotactic body radiation therapy (SBRT) for the treatment of secondary lung tumours in patients who underwent previous pneumonectomy.

Methods:

12 patients were retrospectively analysed. The median maximum tumour diameter was 2.1 cm (1–4.5 cm). The median planning target volume was 20.7 cm³ (2.4–101.2 cm³). Five patients were treated with a single fraction of 26 Gy and seven patients with fractionated schemes (3 × 10 Gy, 4 × 10 Gy, 4 × 12 Gy). Lung toxicity, correlated with volume (V) of lung receiving >5, >10 and >20 Gy, local control and survival rate were assessed. Median follow-up was 28 months.

Results:

None of the patients experienced pulmonary toxicity > grade 2 at the median dosimetric lung parameters of V₅, V₁₀ and V₂₀ of 23.1% (range 10.7–56.7%), 7.3% (2.2–27.2%) and 2.7% (0.7–10.9%), respectively. No patients required oxygen or had deterioration of the performance status during follow-up if not as a result of clinical progression of disease. The local control probability at 2 years was 64.5%, and the overall survival at 2 years was 80%.

Conclusion:

SBRT appears to be a safe and effective modality for treating patients with a second lung tumour after pneumonectomy.

Advances in knowledge:

Our results and similar literature results show that when keeping V₅, V₁₀ V₂₀ <50%, <20% and <7%, respectively, the risk of significant lung toxicity is acceptable. Our experience also shows that biologically effective dose 10 >100 Gy, necessary for high local control rate, can be reached while complying with the dose constraints for most patients.     

Dosimetric planning study for the prevention of anal complications after post-operative whole pelvic radiotherapy in cervical cancer patients with hemorrhoids

Objective:

Radiation-induced anal toxicity can be induced by low radiation doses in patients with haemorrhoids. The object of this study was to determine the dosimetric benefits of different whole pelvic radiotherapy (WPRT) techniques in terms of dose delivered to the anal canal in post-operative patients with cervical cancer.

Methods:

The planning CT images of 10 patients with cervical cancer undergoing postoperative radiotherapy were used for comparison of three different plans. All patients had been treated using the conventional box technique WPRT (CV-WPRT), and we tried low-margin-modified WPRT (LM-WPRT), three-dimensional conformal techniques WPRT (CF-WPRT) and intensity-modulated WPRT (IM-WPRT) planning for dosimetric comparison of the anal canal, retrospectively.

Results:

Mean anal canal doses of the IM-WPRT were significantly lower (p < 0.05) than those of CV-WPRT, LM-WPRT and CF-WPRT, and V₁₀, V₂₀, V₃₀ and V₄₀ to the anal canal were also significantly lower for IM-WPRT (p < 0.05). The proportion of planning target volumes (PTVs) that received ≥98% of the prescribed dose for all plans was >99%, and the proportion that received ≥108% of the prescribed dose for IM-WPRT was <2%. Volumes of bladders and rectums that received ≥30 or ≥40 Gy were significantly lower for IM-WPRT than for three of the four-field WPRT plans (p = 0.000).

Conclusion:

IM-WPRT can significantly reduce radiation dose delivered to the anal canal and does not compromise PTV coverage. In patients with haemorrhoids, IM-WPRT may be of value for the prevention of anal complications.

Advances in knowledge:

Although tolerance of the anal canal tends to be ignored in patients undergoing post-operative WPRT, patients with haemorrhoids may suffer complications at low radiation doses. The present study shows IM-WPRT can be meaningful in these patients.     

Predictors of late bowel toxicity using three different methods of contouring in patients undergoing post-operative radiation for cervical cancer

Objective:

This study investigates the correlation between dose–volume histogram derived from three bowel contouring methods and late toxicity in patients undergoing post-operative radiation therapy (PORT) for cervical cancer.

Methods:

From June 2010 to May 2013, 103 patients undergoing PORT were included. Three different contouring methods were used: (a) individual small bowel (SB) and large bowel (LB) loops, (b) total bowel (TB; including SB and LB) and (c) peritoneal cavity (PC). The volume of SB, LB, TB and PC receiving 15, 30 and 40 Gy was calculated. Acute and late bowel toxicities were scored using Common Terminology Criteria for Adverse events v. 3.0. Receiver operating characteristic curve identified thresholds predicting late toxicity with the highest specificity. All data were dichotomized across these thresholds. Univariate and multivariate analyses were performed using SPSS^® v. 20 (IBM Corporation, Armonk, NY; formerly SPSS Inc., Chicago, IL).

Results:

On univariate analysis, V₃₀ PC ≥ 900 cm³ (p = 0.01), V₄₀ PC ≥ 750 cm³ (p = 0.03) and V₄₀ TB ≥ 280 cm³ (p = 0.03) and use of concurrent chemotherapy (p = 0.03) predicted grade ≥II acute toxicity. On multivariate analysis, use of concurrent chemotherapy [odds ratio (OR) 3.5, 95% confidence interval (CI) 1.1–11.1, p = 0.03] and V₃₀ PC ≥ 900 cm³ (OR 2.3, 95% CI 1–5.5, p = 0.05) predicted acute grade ≥II toxicity. On univariate analysis for late toxicity, SB (V₃₀ ≥ 190 cm³, p = 0.009; V₄₀ ≥ 150 cm³, p = 0.03), LB (V₁₅ ≥ 250 cm³, p = 0.04), V₄₀ PC (V₄₀ ≥ 750 cm³, p = 0.001) and presence of acute grade ≥III toxicity (p = 0.006), treatment technique (three-dimensional conformal radiation or intensity modulated radiotherapy, p = 0.02) predicted more than or equal to grade ll late bowel toxicity. On multivariate analysis, only body mass index ≥25 kg m⁻² (OR 7.3, 95% CI 1.6–31.6, p = 0.008) and presence of acute grade III toxicity predicted toxicity (OR 5.1, 95% CI 1.4–18.1, p = 0.007).

Conclusion:

V₃₀ PC ≥ 900 cm³ and use of concurrent chemotherapy independently predicts acute toxicity. Presence of acute grade ≥III toxicity independently predicts late toxicity. Minimizing dose to PC subvolumes can therefore reduce both acute and late toxicities.

Advances in knowledge:

Study establishes PC thresholds that can minimize both acute and late bowel toxicities.     

Dosimetric benefits of hemigland stereotactic body radiotherapy for prostate cancer: implications for focal therapy

Objective:

Compared with standard, whole-gland (WG) therapies for prostate cancer, focal approaches may provide equivalent oncologic outcomes with fewer adverse effects. The purpose of this study was to compare organ-at-risk (OAR) dosimetry between hemigland (HG) and WG stereotactic body radiotherapy (SBRT) plans.

Methods:

Volumetric-modulated arc radiotherapy-based SBRT plans were designed to treat the left HG, right HG and WG in eight patients, using five fractions of 8 Gy. OARs of interest included the contralateral HG, rectum, urinary bladder, urethra, penile bulb and contralateral neurovascular bundle.

Results:

Rectal V_80% (the percentage of a normal structure receiving a dose of 80%) and V_90% were significantly lower with HG plans than with WG plans (median values of 4.4 vs 2.5 cm³ and 2.1 vs 1.1 cm³, respectively, p < 0.05 by Student''s t-test). Bladder V_50% was also reduced significantly in HG plans (32.3 vs 17.4 cm³, p < 0.05), with a trend towards reduction of V_100% (3.4 vs 1.3 cm³, p = 0.09). Urethral maximum dose and mean doses to the penile bulb and contralateral neurovascular bundle were also reduced significantly (42.0 vs 39.7 Gy, p < 0.00001; 13.3 vs 9.2 Gy, p < 0.05; and 40.2 vs 19.3 Gy, p < 0.00001, respectively).

Conclusion:

Targeting an HG volume rather than a WG volume when delivering SBRT can offer statistically significant reductions for all OARs. Given the large magnitude of the reduction in dose to these OARs, it is anticipated that HG SBRT could offer a superior toxicity profile when compared with WG SBRT. This is likely to be most relevant in the context of salvaging a local failure after radiation therapy.

Advances in knowledge:

The dosimetric feasibility of HG SBRT is demonstrated. When compared with WG SBRT plans, the HG plans demonstrate statistically significant and large magnitude reduction in doses to the rectum, bladder, urethra, penile bulb and contralateral neurovascular bundle, suggesting the possibility of improved toxicity outcomes with HG SBRT. This is likely to be most relevant in the context of salvaging a local failure after radiation therapy.     

Vaginal displacement during course of adjuvant radiation for cervical cancer: results from a prospective IG-IMRT study

Objective:

To compare internal target volume (ITV) generated using population-based displacements (ITV_study) with empty and full bladder scan fusion (ITV_EBFB) for organ-at-risk (OAR) doses during adjuvant intensity-modulated radiation therapy (IMRT) for cervical cancer.

Methods:

From January 2011 to October 2012, patients undergoing IMRT were included. CT simulation was carried out after inserting vault markers. Planning target volume (PTV)_EBFB received 50 Gy per 25 fractions. Pre-treatment megavoltage CT (MVCT) was performed. MVCTs were registered using bony landmarks with Day 1 MVCT. Displacement of the centre of mass of markers was measured along each axis. Directional ITV was calculated using mean ± 2 standard deviations (SDs) (ITV_study). Replanning was performed using PTV study, and OAR doses were compared with PTV_EBFB using Wilcoxon test.

Results:

A total of 348/386 data sets were evaluable for 16 patients. The median vaginal displacement was 1.2 mm (SD, 1.3 mm), 4.0 mm (SD, 3.5 mm) and 2.8 mm (SD, 3.3 mm) in the mediolateral, superoinferior and anteroposterior directions, respectively. The ITV margins were 4.1, 10.3 and 10.6 mm. ITV_study and ITV_EBFB were 115.2 cm³ (87.7–152.2 cm³) and 151 cm³ (95.7–277.1 cm³) (p < 0.0001), respectively. PTV_study and PTV_EBFB were 814 and 881 cm³ (p < 0.0001), respectively. Median doses to the bladder were lower with the PTV_study (46.2 Gy vs 43.2 Gy; p = 0.0001), and a similar trend was observed in the volume of the small bowel receiving 40 Gy (68.2 vs 60.1 cm³; p = 0.09).

Conclusion:

Population-based PTV margins can lead to reduction in OAR doses.

Advances in knowledge:

Population-based ITV may reduce OAR doses while executing adjuvant IMRT for cervical cancer.Adjuvant pelvic radiation for cervical and endometrial cancers is recommended in patients with adverse histopathological features following surgery.^1,2 Although it improves outcomes, it is associated with increased acute and late bowel morbidity.^1,2 Recently published results of the Radiation Therapy Oncology Group (RTOG) Phase II study demonstrate that the use of pelvic intensity-modulated radiation therapy (IMRT) is associated with reduced treatment-related acute and short-term gastrointestinal (GI) toxicity, and this can be achieved without worsening disease control.³ However, implementing IMRT may be challenging owing to the unpredictable nature of vaginal displacements during the course of external radiation. Therefore, the RTOG recommends that for planning IMRT, both empty and full bladder (EBFB) scans should be obtained for localizing residual vagina and for generating the internal target volume (ITV).⁴ These recommendations are being followed by two ongoing Phase III randomized controlled trials that aim at reducing acute and late bowel toxicity of adjuvant pelvic radiation.^5,6 Although this strategy may ensure that all extreme displacements arising out of variations in bladder filling are accounted for, this may result in increased planning target volume (PTV) and thereby increased dose to adjacent organs at risk (OAR). Strong correlation has been reported between the dose received by the bowel and late bowel morbidity after adjuvant pelvic radiation for cervical cancer.⁷ The present study was initiated with an aim of evaluating vaginal displacement for the post-hysterectomy cohort and to investigate if population-based ITV could reduce dose to OARs.     

Submandibular gland sparing in intensity-modulated radiotherapy for N0-stage nasopharyngeal carcinoma

Objective:

This study evaluated and quantified the feasibility of submandibular gland (SMG) sparing in intensity-modulated radiotherapy (IMRT) for N0-stage nasopharyngeal carcinoma (NPC).

Methods:

Ten patients with N0-stage NPC were enrolled in the study. Four IMRT plans were produced for each, with different limiting conditions. In plan A, SMG sparing was ignored; in plans B, C and D, the mean dose to SMGs was restricted to 39 Gy. In addition, at least 95% of planning target volume (PTV)-IIa (PTV of clinical target volume involving level IIa lymph node) in plan C and 90% of PTV-IIa in plan D were required to have a 60 Gy covering.

Results:

The average mean dose to SMGs was 54.6 ± 3.6 Gy in plan A and was lower 39.3 ± 0.3, 49.3 ± 1.9 and 46.7 ± 2.8 Gy in plans B, C and D, respectively. The volume of PTV-IIa covered by 60 Gy was 98.9%, 81.6%, 95.2% and 90.8% in plans A, B, C and D, respectively, and showed a parallel association between dose reduction to SMGs and the covering deficit of PTV-IIa.

Conclusion:

Reducing the mean dose received by SMG to 39 Gy or less in IMRT for N0-stage NPC is feasible.Xerostomia is the most prevalent sequela following radiotherapy of nasopharyngeal carcinoma (NPC),¹ but can be reduced by parotid gland sparing using intensity-modulated radiotherapy (IMRT) techniques. In recent years, the submandibular gland (SMG) was found to play an important role in the secretion of saliva,^2,3 contributing up to 90% of unstimulated salivary output as well as contributing to a patient''s subjective sense of moisture. Therefore, sparing the SMGs from high-dose irradiation would be useful in reducing the symptoms of xerostomia.SMGs are located inside the area of neck node level Ib and anterior to the level II region. Level II neck nodes are generally elected to receive prophylactic irradiation. It has been reported that with three-dimensional conformal radiotherapy for head and neck cancers,⁴ the SMGs would receive an unplanned dose of 62 Gy on average. Preservation of SMG function was reported for head and neck cancer treated with IMRT.^5–7 However, data from our institution showed that the average unplanned dose received by SMGs was 58 Gy in IMRT of N0-stage NPC, although level I neck nodes were omitted for selected irradiations.To our knowledge, the abovementioned studies focused only on the contralateral SMG (cSMG).^5–7 However, is it possible to spare the bilateral SMGs in N0-stage NPC patients but what will be the subsequent trade-off of dose distribution to planning target volume 1 (PTV1) around the SMG area? This study was designed to address this question, and the results will be a valuable reference in planning the IMRT of NPC.     

Simultaneous integrated boost to intraprostatic lesions using different energy levels of intensity-modulated radiotherapy and volumetric-arc therapy

Objective:

This study compared the dosimetry of volumetric-arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) with a dynamic multileaf collimator using the Monte Carlo algorithm in the treatment of prostate cancer with and without simultaneous integrated boost (SIB) at different energy levels.

Methods:

The data of 15 biopsy-proven prostate cancer patients were evaluated. The prescribed dose was 78 Gy to the planning target volume (PTV78) including the prostate and seminal vesicles and 86 Gy (PTV86) in 39 fractions to the intraprostatic lesion, which was delineated by MRI or MR-spectroscopy.

Results:

PTV dose homogeneity was better for IMRT than VMAT at all energy levels for both PTV78 and PTV86. Lower rectum doses (V₃₀–V₅₀) were significantly higher with SIB compared with PTV78 plans in both IMRT and VMAT plans at all energy levels. The bladder doses at high dose level (V₆₀–V₈₀) were significantly higher in IMRT plans with SIB at all energy levels compared with PTV78 plans, but no significant difference was observed in VMAT plans. VMAT plans resulted in a significant decrease in the mean monitor units (MUs) for 6, 10, and 15 MV energy levels both in plans with and those without SIB.

Conclusion:

Dose escalation to intraprostatic lesions with 86 Gy is safe without causing serious increase in organs at risk (OARs) doses. VMAT is advantageous in sparing OARs and requiring less MU than IMRT.

Advances in knowledge:

VMAT with SIB to intraprostatic lesion is a feasible method in treating prostate cancer. Additionally, no dosimetric advantage of higher energy is observed.Randomized trials have shown a gain in biochemical relapse-free survival using dose escalation for prostate cancer.¹ However, isolated local failure is still reported in nearly one-third of patients, even with higher radiotherapy (RT) doses.¹ Local recurrence is of clinical importance because a relationship has been suggested between local control, distant metastasis and survival.² It has also been demonstrated that intraprostatic failure mainly originates at the initial tumour location as a result of intrinsic resistance of a fraction of the tumour clones, which implies that selective dose escalation to the dominant intraprostatic lesion using simultaneous integrated boost (SIB) might be beneficial.³With new RT techniques, such as intensity-modulated RT (IMRT) and volumetric-arc therapy (VMAT), SIB could be delivered without increasing acute toxicity.^4–7 Several recent studies have performed dosimetric comparison of IMRT and VMAT plans in prostate cancer;^8–10 however, dosimetric evaluation of IMRT and VMAT plans delivering SIB is rare. In these studies, target volume and organs at risk (OARs) doses may vary with different treatment planning systems. Another aspect not often addressed in these planning studies is the photon energy level.^4,8,9,11 Although higher energy photons have the potential advantage of reduced attenuation with depth, this may in turn increase the risk of secondary malignancies because of the presence of neutrons generated in the accelerator head at treatment energies >8 MV.¹²Functional imaging techniques can clearly demonstrate tumour within the prostate. MRI, MR spectroscopy (MRS) and positron emission tomography are capable of demonstrating intraprostatic lesions (IPLs).¹³ The advent of combined MRI with MRS or dynamic contrast enhanced (DCE)-MRI improves the detection rate of tumours within the prostate.^13–15The aim of the present study was to make dosimetric comparisons of VMAT and 7-field IMRT with dynamic multileaf collimators (MLCs) using the Monte Carlo algorithm with XVMC code in the treatment of prostate cancer with or without SIB, which can provide improved dose calculation accuracy and has been implemented successfully in the clinical setting.^16,17 Additionally, the impact of three photon energies on target volumes, OARs and normal tissue was evaluated in IMRT and VMAT plans.     

Effect on therapeutic ratio of planning a boosted radiotherapy dose to the dominant intraprostatic tumour lesion within the prostate based on multifunctional MR parameters

Objective:

To demonstrate the feasibility of an 8-Gy focal radiation boost to a dominant intraprostatic lesion (DIL), identified using multiparametric MRI (mpMRI), and to assess the potential outcome compared with a uniform 74-Gy prostate dose.

Methods:

The DIL location was predicted in 23 patients using a histopathologically verified model combining diffusion-weighted imaging, dynamic contrast-enhanced imaging, T₂ maps and three-dimensional MR spectroscopic imaging. The DIL defined prior to neoadjuvant hormone downregulation was firstly registered to MRI-acquired post-hormone therapy and subsequently to CT radiotherapy scans. Intensity-modulated radiotherapy (IMRT) treatment was planned for an 8-Gy focal boost with 74-Gy dose to the remaining prostate. Areas under the dose–volume histograms (DVHs) for prostate, bladder and rectum, the tumour control probability (TCP) and normal tissue complication probabilities (NTCPs) were compared with those of the uniform 74-Gy IMRT plan.

Results:

Deliverable IMRT plans were feasible for all patients with identifiable DILs (20/23). Areas under the DVHs were increased for the prostate (75.1 ± 0.6 vs 72.7 ± 0.3 Gy; p < 0.001) and decreased for the rectum (38.2 ± 2.5 vs 43.5 ± 2.5 Gy; p < 0.001) and the bladder (29.1 ± 9.0 vs 36.9 ± 9.3 Gy; p < 0.001) for the boosted plan. The prostate TCP was increased (80.1 ± 1.3 vs 75.3 ± 0.9 Gy; p < 0.001) and rectal NTCP lowered (3.84 ± 3.65 vs 9.70 ± 5.68 Gy; p = 0.04) in the boosted plan. The bladder NTCP was negligible for both plans.

Conclusion:

Delivery of a focal boost to an mpMRI-defined DIL is feasible, and significant increases in TCP and therapeutic ratio were found.

Advances in knowledge:

The delivery of a focal boost to an mpMRI-defined DIL demonstrates statistically significant increases in TCP and therapeutic ratio.Phase III trials using conformal external beam radiotherapy have shown that a dose escalation improves biochemical progression-free survival in patients with prostate cancer;^1–5 however, increases in late rectal and urinary morbidity are associated with the dose distributions used to achieve these gains.With the advent of intensity-modulated radiotherapy (IMRT), complex three-dimensional (3D) dose distributions can be delivered to areas of disease whilst reducing the dose to the surrounding tissues and also potentially boosting the dose to encompassed small volumes such as the dominant intraprostatic lesions (DILs). This is potentially advantageous, as local recurrence has been shown to originate within the initial tumour volume.⁶This approach requires reliable and reproducible imaging to identify the DIL. Conventional MR using high spatial resolution T₂ weighted (T2W) contrast has insufficient sensitivity and specificity for defining the tumour within the prostate gland, especially if the lesions are <1 cm in diameter.⁷ A combination of MRI methods whose contrast is determined by tissue physiology and biochemistry rather than anatomy offers improved sensitivity and specificity for delineation of prostate cancers. Functional methods include diffusion-weighted imaging, MR spectroscopic imaging (MRSI) and dynamic contrast-enhanced MRI (DCE-MRI) and together present a multiparametric MRI (mpMRI) data set. We have previously validated a multiparametric model to identify prostate cancer and the location of DILs with histology from prostatectomy specimens.⁸mpMRI data are reliable only if acquired before androgen deprivation (hormone) therapy, as there is profound functional signal degradation after hormone therapy.^9–11 Our standard institutional practice for intermediate- and high-risk localized prostate cancer uses hormone therapy for 3–6 months prior to external beam radiotherapy,^12–14 so modelling a radiation boost to mpMRI-defined tumour nodules requires acquisition of functional data before hormone therapy to be registered with anatomical images obtained post hormone treatment and immediately prior to radiotherapy¹⁵ in order to translate the tumour location to radiotherapy planning CT images. The aim of this planning study therefore was to demonstrate the use of a mpMRI-defined DIL to create a radiotherapy boost volume. IMRT treatment plans were optimized to deliver either a uniform 74 Gy to the whole prostate or to add an 8-Gy simultaneous integrated boost to the DIL, and the potential clinical outcomes compared using dose–volume histograms (DVHs) and radiobiological models for tumour control probability (TCP) and normal tissue complication probabilities (NTCPs).     

Parametrized rectal dose and associations with late toxicity in prostate cancer radiotherapy

Objective:

We investigated possible associations between planned dose–volume parameters and rectal late toxicity in 170 patients having radical prostate cancer radiotherapy.

Methods:

For each patient, the rectum was outlined from anorectal junction to sigmoid colon, and rectal dose was parametrized using dose–volume (DVH), dose–surface (DSH) and dose–line (DLH) histograms. Generation of DLHs differed from previous studies in that the rectal dose was parametrized without first unwrapping onto 2-dimensional dose–surface maps. Patient-reported outcomes were collected using a validated Later Effects in Normal Tissues Subjective, Objective, Management and Analytic questionnaire. Associations between dose and toxicity were assessed using a one-sided Mann–Whitney U test.

Results:

Associations (p < 0.05) were found between equieffective dose (EQD2₃) and late toxicity as follows: overall toxicity with DVH and DSH at 13–24 Gy; proctitis with DVH and DSH at 25–36 Gy and with DVH, DSH and DLH at 61–67 Gy; bowel urgency with DVH and DSH at 10–20 Gy. None of these associations met statistical significance following the application of a Bonferroni correction.

Conclusion:

Independently confirmed associations between rectal dose and late toxicity remain elusive. Future work to increase the accuracy of the knowledge of the rectal dose, either by accounting for interfraction and intrafraction rectal motion or via stabilization of the rectum during treatment, may be necessary to allow for improved dose–toxicity comparisons.

Advances in knowledge:

This study is the first to use parametrized DLHs to study associations with patient-reported toxicity for prostate radiotherapy showing that it is feasible to model rectal dose mapping in three dimensions.     

Acute effects of pelvic irradiation on the adult uterus revealed by dynamic contrast-enhanced MRI

Objective:

Pelvic radiation therapy (RT) can influence fertility in female rectal cancer survivors. Data regarding its effects on the adult uterus are scant. This study aims to evaluate the uterus before and after RT, using dynamic contrast-enhanced MRI.

Methods:

Eligible patients (n=10) received RT for rectal cancer, had an intact uterus and underwent dynamic contrast-enhanced MRI before and after RT. Seven patients were pre-menopausal.

Results:

Patients received pelvic RT (median, 50.2 Gy) with concurrent 5-fluorouracil. Five patients were treated with intensity modulated RT (IMRT) and five with a three-field technique. The median D95 of the uterus was 30 Gy; D05 was 48 Gy; and V95 was 97%. The median cervical D95 was 45 Gy; D05, 50 Gy; and V95, 100%. Cervical dose was higher with IMRT than with three-field plans (p≤0.038). On T₂ MRI, the junctional zone was visible in nine patients before and in one after RT (p=0.001). Median cervical length (2.3 vs 3.0 cm) and endometrial thickness (2.6 vs 5.9 mm) were reduced after RT (p≤0.008). In pre-menopausal patients, the volume transfer constant, K_trans, (0.069 vs 0.195, p=0.006) and the extracellular extravascular volume fraction, V_e, (0.217 vs 0.520, p=0.053) decreased.

Conclusion:

Pelvic RT significantly affected uterine anatomy and perfusion. Cervical dose was higher with IMRT than three-field plans, but no attempt was made to constrain the dose.

Advances in knowledge:

Pelvic RT significantly affects the adult uterus. These findings are crucial to understand the potential consequences of RT on fertility, and they lay the groundwork for further prospective studies.As the cure rate in locally advanced rectal cancer continues to improve, understanding the long-term sequelae of therapy is gaining importance. Research has shown that young cancer survivors are concerned about treatment-related effects on fertility, pregnancy and neonatal outcomes [1,2]. Previously, pelvic irradiation, standard in the management of locally advanced rectal cancer, invariably caused sterility in females as a result of acute ovarian failure. Currently, however, the risk of ovarian dysfunction may be greatly reduced by transposing the ovaries to the paracolic gutters before radiation therapy (RT) [3]. Additionally, an increasing number of females undergo embryo or oocyte cryopreservation before receiving RT [4]. These advances prompt the question: if a young female has undergone pelvic RT, can she carry a pregnancy to term?Answering this question requires an understanding of the effects of the pelvic RT on the uterus. Ultrasounds of paediatric cancer survivors suggest that pelvic RT alters uterine volume, distensibility and vasculature, with patients who are younger at the time of RT being the most vulnerable to these effects [5–7]. Additionally, population-based studies of paediatric cancer survivors have demonstrated an association between abdominal and/or pelvic RT and adverse pregnancy and neonatal outcomes, including placental abnormalities, pre-term delivery, low birth weight infants and perinatal mortality [8–11]. However, only sparse data exist regarding the effects of pelvic RT on the adult uterus, which may be more radioresistant.The aim of this study was to use dynamic contrast-enhanced (DCE) MRI to assess the acute effects of RT on the uterus in females treated for locally advanced rectal cancer. A second aim was to compare dosimetric parameters of conventional three-field RT and intensity modulated RT (IMRT) treatment plans.     

Consequences of additional use of contrast-enhanced 18F-FDG PET/CT in target volume delineation and dose distribution for pancreatic cancer

Objective:

To compare the differences between contrast-enhanced (CE) fluorine-18 fludeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/CT and CECT in target volume delineation and radiotherapy (RT) dose distribution, and to evaluate the sparing of organs at risk (OARs) in the treatment plan of locally advanced pancreatic cancer (LAPC).

Methods:

21 consecutive patients with LAPC with histologically or cytologically confirmed adenocarcinoma underwent both non-CECT and ¹⁸F-FDG scans; 11 of whom also underwent CECT scans. Intensity-modulated RT plans (prescribed dose, 54 Gy) were constructed to cover the corresponding gross tumour volume (GTV). The differences among GTV_CT, GTV_PET, GTV_PET-CT and OARs in these different image sets as well as the uniformity of target dose were analysed.

Results:

The mean non-CE GTV_CT, GTV_PET and GTV_PET-CT were 76.9 ± 47.8, 47.0 ± 40.2 and 44.5 ± 34.7 cm³ (mean ± standard deviation), respectively. The non-CE GTV_PET-CT was significantly smaller than the non-CE GTV_CT (p < 0.001). The CE GTV_PET-CT was significantly smaller than the CE GTV_CT (p = 0.033). For both the non-CE GTV_CT and the CE GTV_CT, the intestine V₄₀ (the percentage of the intestine volume irradiated by 40 Gy), intestine V₅₀, intestine D_max (the mean maximum dose), cord D_max, left kidney V₃₀, right kidney V₃₀, left kidney D_mean (the mean dose), right kidney D_mean and liver V₃₀ were 5.90%, 2.52%, 5500 cGy, 2194 cGy, 3.40%, 0.68%, 747 cGy, 550 cGy and 5.37%, respectively. There are significant differences between the non-CE CT and the non-CE PET-CT in intestine D_max (p = 0.023) and right kidney D_mean (p = 0.029).

Conclusion:

Co-registration of ¹⁸F-FDG PET with CECT may improve the accuracy of GTV delineation in LAPC and might reduce the adverse effect of irradiation.

Advances in knowledge:

Individual adaptation of RT based on functional CE ¹⁸F-FDG PET/CT imaging is possible and highly promising in LAPC.Pancreatic cancer (PC) is the fourth most common cause of cancer death in the USA with 5-year overall survival (OS) rates of <5%.¹ PC is a notoriously insidious disease, and about 70% of patients newly diagnosed with this malignancy are not amenable to curative surgery.² Concurrent chemoradiotherapy is the main treatment for locally advanced or recurrent PC, and radiotherapy (RT) plays a key role for local control. There are still many unresolved issues related to the delineation of the gross tumour volume (GTV) in locally advanced PC (LAPC), such as the difficulty in distinguishing the vasculature from tumour parenchyma, defining the tumour boundary on contrast-enhanced CT (CECT) in the absence of functional positron emission tomography (PET) imaging, and the presence of adjoining organs at risk (OARs), such as the small intestine, spinal cord, kidney and liver. The delineation of the GTV based on PET-CT fusion images could improve RT planning by reducing the target volume and the exposure volumes of the respective OARs and safely escalating the target radiation dose. Conventional enhanced CT scanning could not identify the extent of local tumour and lymph node invasion from peripheral structures precisely,³ which may result in inaccurate target delineation.Our study aimed to explore the value of the CE fluorine-18 fludeoxyglucose (¹⁸F-FDG) PET-CT fusion images for target volume delineation, dose distribution in OARs and the uniformity of target dose compared with the results of CT scan-based plans in LAPC.     

SmartArc-based volumetric modulated arc therapy can improve the middle ear,vestibule and cochlea sparing for locoregionally advanced nasopharyngeal carcinoma: a dosimetric comparison with step-and-shoot intensity-modulated radiotherapy

Objective:

Radiation-induced sensorineural hearing loss is a common complication after radiotherapy in patients with nasopharyngeal carcinoma (NPC) that significantly affects their quality of life. The goal of this study was to compare SmartArc-based volumetric modulated arc therapy (VMAT-S) with step-and-shoot intensity-modulated radiation therapy (IMRT) for patients with locoregionally advanced NPC with regard to the sparing effect on middle ear, vestibule and cochlea.

Methods:

20 patients with non-metastatic Stage III or IV NPC were selected to have planning with VMAT-S and IMRT [using Philips Pinnacle Planning System (Philips, Fitchburg, WI) for Varian accelerator] for dosimetric comparison. Mean middle ears, vestibule and cochlea doses for the two planning techniques were compared using a paired t-test. Target coverage and dose homogeneity were evaluated by calculating conformity index (CI) and homogeneity index (HI) values.

Results:

VMAT-S had significantly improved homogeneity and conformity compared with IMRT. Mean HI of planning target volume of gross tumour volume (PGTV) was better with VMAT-S (1.05 ± 0.02) than IMRT (1.09 ± 0.03) (p < 0.001). Mean CI of PGTV is also better with VMAT-S (0.59 ± 0.12) than IMRT (0.54 ± 0.12) (p < 0.001). Mean doses to the left cochleas were 43.8 ± 3.6 and 47.8 ± 4.0 (p < 0.001) for VMAT-S and IMRT plans, respectively. Mean doses to the right cochleas were 42.7 ± 4.7 and 47.6 ± 5.4 (p < 0.001) for VMAT-S and IMRT plans, respectively. VMAT-S also significantly reduced the mean doses to middle ears (p < 0.001 for both) and vestibule (p < 0.001 for both).

Conclusion:

Our results indicate that VMAT-S provides better sparing of hearing apparatus in locoregionally advanced NPC.

Advances in knowledge:

VMAT-S can improve the middle ear, vestibule and cochlea sparing in patients with locoregionally advanced NPC.     

Dose–volume-related dysphagia after constrictor muscles definition in head and neck cancer intensity-modulated radiation treatment

Objective:

Dysphagia remains a side effect influencing the quality of life of patients with head and neck cancer (HNC) after radiotherapy. We evaluated the relationship between planned dose involvement and acute and late dysphagia in patients with HNC treated with intensity-modulated radiation therapy (IMRT), after a recontouring of constrictor muscles (PCs) and the cricopharyngeal muscle (CM).

Methods:

Between December 2011 and December 2013, 56 patients with histologically proven HNC were treated with IMRT or volumetric-modulated arc therapy. The PCs and CM were recontoured. Correlations between acute and late toxicity and dosimetric parameters were evaluated. End points were analysed using univariate logistic regression.

Results:

An increasing risk to develop acute dysphagia was observed when constraints to the middle PCs were not respected [mean dose (D_mean) ≥50 Gy, maximum dose (D_max) >60 Gy, V50 >70% with a p = 0.05]. The superior PC was not correlated with acute toxicity but only with late dysphagia. The inferior PC was not correlated with dysphagia; for the CM only, D_max >60 Gy was correlated with acute dysphagia ≥ grade 2.

Conclusion:

According to our analysis, the superior PC has a major role, being correlated with dysphagia at 3 and 6 months after treatments; the middle PC maintains this correlation only at 3 months from the beginning of radiotherapy, but it does not have influence on late dysphagia. The inferior PC and CM have a minimum impact on swallowing symptoms.

Advances in knowledge:

We used recent guidelines to define dose constraints of the PCs and CM. Two results emerge in the present analysis: the superior PC influences late dysphagia, while the middle PC influences acute dysphagia.In the past decade, substantial progress has been made in the treatment of head and neck cancer (HNC). Several reports show that radiotherapy (RT) with concomitant chemotherapy or altered fractionation schedules improve tumour control and survival rate.^1,2However, xerostomia and dysphagia often remain relevant side effects for patients with HNC, compromising their quality of life (QoL), as a consequence of radiation damage to the parotid glands and to the organ at risk (OAR) involved in the swallowing process (SWOARs).³Intensity-modulated radiation therapy (IMRT) and rotational intensity-modulated techniques, including volumetric-modulated arc therapy (VMAT), allow for a better dose conformation to target structures while reducing the dose.^4–8 In comparison with three-dimensional-conformal radiation therapy, several studies have shown that IMRT in HNC treatment reduces overall adverse effects such as xerostomia and dysphagia and thus improves QoL, even when chemotherapy is added.^9–13Regarding tolerance of the parotid glands, several studies have suggested significant recovery when the mean dose is inferior to 26 Gy. Open questions remain for SWOARs, especially with reference to the delineation modalities of the involved structures to the volumes or the dose constraints to be applied.^14–18 More authors hypothesized that sparing a portion of the constrictor muscles (PCs), not involved by tumour and not at risk of subclinical disease, might reduce dysphagia.^19–21 These studies obtained different results, maybe, owing to a number of methodological issues and to the ambiguous contouring of the PCs. For this purpose, Christianen et al²² recently defined guidelines for SWOARs contouring.Based on these findings, the aim of this retrospective analysis is to evaluate potential relationships between planned dose–volume parameters and observed incidence of acute and late dysphagia in patients with HNC treated with IMRT or VMAT, after a recontouring of the PCs according to these recently published guidelines.     

Volumetric-modulated arc stereotactic body radiotherapy for prostate cancer: dosimetric impact of an increased near-maximum target dose and of a rectal spacer

Objective:

In volumetric-modulated arc therapy (VMAT) prostate stereotactic body radiotherapy (SBRT), dose coverage of the planning target volume (PTV) becomes challenging when the sparing of rectum, bladder and urethra is strictly pursued. Our current 35-Gy-in-five-fraction plans only assure 33.2 Gy to ≥95% PTV (V33.2PTV ≥ 95%). Looking for an improved V33.2PTV, increased near-maximum target dose (D_2%) and prostate–rectum spacer insertion were tested.

Methods:

For 11 patients, two VMAT plans, with D_2% ≤ 37.5 Gy (Hom) or D_2% ≤ 40.2 Gy (Het), on each of two CT studies, before or after spacer insertion, were computed. All plans assured V33.2PTV ≥95%, and <1 cm³ of rectum, bladder and urethra receiving ≥35 Gy. By hypothesis testing, several dose–volume metrics for target coverage and rectal sparing were compared across the four groups of plans. The impact of spacer insertion on the fractions of rectum receiving more than 18, 28 and 32 Gy (VXr) was further tested by linear correlation analysis.

Results:

By hypothesis testing, the increased D_2% was associated with improvements in target coverage, whereas spacer insertion was associated with improvements in both target coverage and rectal VXr. By linear correlation analysis, spacer insertion was related to the reductions in rectal VXr for X ≥ 28 Gy.

Conclusion:

A slightly increased D_2% or the use of spacer insertion was each able to improve V33.2PTV. Their combined use assured V33.2PTV ≥ 98% to all our patients. Spacer insertion was further causative for improvements in rectal sparing.

Advances in knowledge:

For VMAT plans in prostate SBRT, the distinct dosimetric usefulness of increased D_2% and of the use of spacer insertion were validated in terms of target coverage and rectal sparing.     

Dosimetric effects of roll rotational setup errors on lung stereotactic ablative radiotherapy using volumetric modulated arc therapy

Objective:

To evaluate the dosimetric effects of roll-rotational setup errors of stereotactic ablative radiotherapy (SABR) for lung cancer using volumetric modulated arc therapy (VMAT).

Methods:

A total of 23 lung SABR cases were evaluated retrospectively. Each of the planning CT images was intentionally rotated by ±1°, ±2° and ±3°. After that, to simulate the translational couch correction, rotated CT images were moved along the x, y and z axis to match the centroid of the target volume in the rotated CT images with that in the original CT images. The differences in D_95% and V_100% of the target volume, D_0.35cc of spinal cord, D_0.35cc and D_5cc of oesophagus and V_20Gy of lung between the original and the rotated CT images were calculated.

Results:

The average differences in D_95% and V_100% of target volume, D_0.35cc of spinal cord, D_0.35cc and D_5cc of oesophagus and V_20Gy of lung were −0.3% ± 0.4% and −0.7% ± 2.4%, 1.6 ± 27.9 cGy, −1.6 ± 37.6 cGy, 15.9 ± 25.3 cGy and 0.0% ± 0.1%, respectively. The dosimetric changes in organs at risk (OARs) near the target volume were sometimes considerable due to roll-rotational setup errors, despite the translational correction, and those were patient specific.

Conclusion:

In the case of coplanar VMAT for lung SABR, dosimetric changes to the target volume due to roll-rotational setup errors could be compensated by translational correction, whereas those to the OARs could not in some cases.

Advances in knowledge:

Roll-rotational setup errors would increase the dose to OARs despite the translational correction.     

Intensity-modulated radiotherapy (IMRT) to prostate and pelvic nodes—is pelvic lymph node coverage adequate with fiducial-based image-guided radiotherapy?

Objective:

There remains concern regarding the use of fiducial-based image-guided radiotherapy (IGRT) in patients with high-risk prostate cancer also undergoing intensity-modulated radiotherapy (IMRT) to pelvic nodes. By a retrospective study, we aim to ascertain the impact of the use of fiducial-based IGRT on lymph node planned target volume (PTV) coverage.

Methods:

30 consecutive IMRT prostate and pelvic node plans were reviewed, and dose was recalculated with 1-mm increment movements in anterior, posterior, superior, inferior, right and left directions up to 10 mm. All patients were treated with a full bladder after drinking 450–750 ml of water and empty rectum with the use of sodium citrate enemas daily. Dose–volume histogram parameters were recorded at each position, specifically nodal PTV V95%, V99% and V100%. A local IGRT database was used to identify the likelihood of a particular bony to fiducial offset in all directions. The combined data were used to calculate the percentage risk of underdosing the lymph node PTV on any given fraction.

Results:

The likelihood of an offset in the left, right and anterior directions occurring and resulting in a failure to cover the PTV was <0.25%. The likelihood of a posterior offset occurring and resulting in inadequate coverage was slightly higher but remained <1%.

Conclusion:

This study confirms the safety of fiducial-based image-guided IMRT (IG-IMRT) with a strict bowel and bladder protocol, allowing a reduction of the clinical target volume to PTV margin of the prostate volume and consequent reduction in rectal toxicity.

Advances in knowledge:

This study strengthens the evidence supporting the safe implementation of fiducial-based IG-IMRT treating the prostate and pelvic nodes in high-risk prostate cancer.Intensity-modulated radiotherapy (IMRT) is the standard of care in radical radiotherapy for prostate cancer.¹ In IMRT delivery, the accuracy of the planned target volume (PTV) definition is critically important as steep dose gradients may increase the risk of geographical miss.² One of the significant potential errors in prostate radiotherapy arises from prostate motion, the mean and maximum of which are reportedly 4–6 and 8–18 mm, respectively.^3–8 The margin from clinical target volume (CTV) to PTV is intended to minimize errors associated with prostate movement during radiation delivery, planning system and delivery uncertainties, as well as daily set-up error.⁹Online fiducial-based image-guided radiotherapy (IGRT) uses a minimum of three fiducial markers inserted into the prostate gland for verification and patient realignment. Paired planar tube potential images are taken prior to the treatment and the fiducial position is matched to the planning CT scan. This corresponding shift is performed prior to the treatment, minimizing any systematic error from patient set-up and the random interfraction prostate motion.¹⁰ Some reports state that online IGRT allows CTV to PTV margins to be reduced to as little as 2 mm,¹¹ although with the residual intrafraction error perhaps a more realistic margin is 4 mm, as suggested by McNair et al.¹² Owing to the reduced margin and resultant decrease in rectal dose and toxicity, IGRT is the standard of care for patients receiving radical radiotherapy for localized prostate cancer, with many centres opting for fiducial-based IGRT.In addition to improved radiotherapy delivery techniques, the landmark Radiation Therapy Oncology Group (RTOG) 9413 study demonstrated a statistically significant 7-year progression-free survival (PFS) benefit, in the subset of patients who received neoadjuvant and concurrent hormonal therapy, of 40% vs 27% using the whole pelvis compared with prostate-only radiotherapy.¹³ This is a controversial area as prospective randomized trials attempted before the RTOG 9413 failed to demonstrate any statistically significant advantage with whole pelvis radiotherapy vs prostate-only radiotherapy.^14,15 In addition, these studies were not powered to identify an overall survival benefit; therefore, there is no evidence that it affects overall survival. Owing to significantly increased toxicity with this technique, some clinicians believe that the risks outweigh the potential benefits. To minimize toxicity and improve lymph node coverage, IMRT has been used in this setting.^16,17A review article by Kaidar-Person et al¹⁸ highlights the issues of using fiducial-based prostate IGRT for patients requiring simultaneous nodal irradiation. The lymph node target coverage may be compromised because lymph nodes and the prostate are moving independently.¹⁹ As a result, matching to fiducials may result in underdosing of the nodes. To prevent this, when delivering IMRT to pelvic nodes, many radiotherapy centres perform IGRT based on a bony match to the planning CT, rather than fiducials. However, when using a bony match, the prostate CTV to PTV margin is necessarily larger, resulting in larger rectal doses and consequently more toxicity.Previous reports on the use of fiducial-based IGRT with IMRT in prostate and nodal irradiation used very small sample sizes.^11,20,21 Hsu et al²⁰ studied five cases, applying each daily fiducial-based IGRT shift to the IMRT treatment course and concluded negligible differences in pelvic lymph node or normal tissue dose, with <1.5% difference in dose delivered. Chung et al¹¹ compared 10 bony IGRT cases with 15 fiducial-based IGRT cases. They reported reduced lymph node coverage with fiducial-based image-guided IMRT (IG-IMRT), which in their opinion was unlikely to lead to clinical detriment. Rossi et al²¹ reviewed daily treatments for 10 patients treated with fiducial-based IG-IMRT by monitoring the nodal PTV coverage in comparison with the planned coverage. They confirmed, providing no systematic shift occurred, a 2.2% degradation to the planned nodal dose.²¹ In an ideal setting, the population-based data would be used to calculate an accurate CTV to PTV margin for the lymph nodes using IG-IMRT, in the manner of van Herk et al;²² however, in reality to maintain an acceptable toxicity in view of the questionable benefit, the dose coverage is often limited to achieve small bowel constraints. With an increasing number of centres moving to fiducial-based prostate IGRT, there is a requirement for more robust evidence of safe lymph node coverage using this technique before a change in practice.We aim to perform a retrospective study to assess the prophylactic dose coverage of lymph nodes when treated with fiducial-based IG-IMRT.