The impact of anatomical changes during photon or proton based radiation treatment on tumor dose in glioblastoma dose escalation trials.

PURPOSE/OBJECTIVE: Most dose-escalation trials in glioblastoma patients integrate the escalated dose throughout the standard course by targeting a specific subvolume. We hypothesize that anatomical changes during irradiation may affect the dose coverage of this subvolume for both proton- and photon-based radiotherapy. MATERIAL AND METHODS: For 24 glioblastoma patients a photon- and proton-based dose escalation treatment plan (of 75 Gy/30 fr) was simulated on the dedicated radiotherapy planning MRI obtained before treatment. The escalated dose was planned to cover the resection cavity and/or contrast enhancing lesion on the T1w post-gadolinium MRI sequence. To analyze the effect of anatomical changes during treatment, we evaluated on an additional MRI that was obtained during treatment the changes of the dose distribution on this specific high dose region. RESULTS: The median time between the planning MRI and additional MRI was 26 days (range 16-37 days). The median time between the planning MRI and start of radiotherapy was relatively short (7 days, range 3-11 days). In 3 patients (12.5%) changes were observed which resulted in a substantial deterioration of both the photon and proton treatment plans. All these patients underwent a subtotal resection, and a decrease in dose coverage of more than 5% and 10% was observed for the photon- and proton-based treatment plans, respectively. CONCLUSION: Our study showed that only for a limited number of patients anatomical changes during photon or proton based radiotherapy resulted in a potentially clinically relevant underdosage in the subvolume. Therefore, volume changes during treatment are unlikely to be responsible for the negative outcome of dose-escalation studies.

Characterization of automatic treatment planning approaches in radiotherapy.

BACKGROUND AND PURPOSE: Automatic approaches are widely implemented to automate dose optimization in radiotherapy treatment planning. This study systematically investigates how to configure automatic planning in order to create the best possible plans. MATERIALS AND METHODS: Automatic plans were generated using protocol based automatic iterative optimization. Starting from a simple automation protocol which consisted of the constraints for targets and organs at risk (OAR), the performance of the automatic approach was evaluated in terms of target coverage, OAR sparing, conformity, beam complexity, and plan quality. More complex protocols were systematically explored to improve the quality of the automatic plans. The protocols could be improved by adding a dose goal on the outer 2 mm of the PTV, by setting goals on strategically chosen subparts of OARs, by adding goals for conformity, and by limiting the leaf motion. For prostate plans, development of an automated post-optimization procedure was required to achieve precise control over the dose distribution. Automatic and manually optimized plans were compared for 20 head and neck (H&N), 20 prostate, and 20 rectum cancer patients. RESULTS: Based on simple automation protocols, the automatic optimizer was not always able to generate adequate treatment plans. For the improved final configurations for the three sites, the dose was lower in automatic plans compared to the manual plans in 12 out of 13 considered OARs. In blind tests, the automatic plans were preferred in 80% of cases. CONCLUSIONS: With adequate, advanced, protocols the automatic planning approach is able to create high-quality treatment plans.

Predicting and implications of target volume changes of brain metastases during fractionated stereotactic radiosurgery.

OBJECTIVE: To study the impact of target volume changes in brain metastases during fractionated stereotactic radiosurgery (fSRS) and identify patients that benefit from MRI guidance. MATERIAL AND METHODS: For 15 patients (18 lesions) receiving fSRS only (fSRSonly) and 19 patients (20 lesions) receiving fSRS postoperatively (fSRSpostop), a treatment planning MRI (MR0) and repeated MRI during treatment (MR1) were acquired. The impact of target volume changes on the target coverage was analyzed by evaluating the planned dose distribution (based on MR0) on the planning target volume (PTV) during treatment as defined on MR1. The predictive value of target volume changes before treatment (using the diagnostic MRI (MRD)) was studied to identify patients that experienced the largest changes during treatment. RESULTS: Target volume changes during fSRS did result in large declines of the PTV dose coverage up to -34.8% (median = 3.2%) for fSRSonly patients. For fSRSpostop the variation and declines were smaller (median PTV dose coverage change = -0.5% (-4.5% to 1.9%)). Target volumes changes did also impact the minimum dose in the PTV (fSRSonly; -2.7 Gy (-16.5 to 2.3 Gy), fSRSpostop; -0.4 Gy (-4.2 to 2.5 Gy)). Changes in target volume before treatment (i.e. seen between the MRD and MR0) predicted which patients experienced the largest dose coverage declines during treatment. CONCLUSION: Target volume changes in brain metastases during fSRS can result in worsening of the target dose coverage. Patients benefiting the most from a repeated MRI during treatment could be identified before treatment.

Radiation dose to the masseter and medial pterygoid muscle in relation to trismus after chemoradiotherapy for advanced head and neck cancer.

BACKGROUND: We studied the relationship between trismus (maximum interincisor opening [MIO] ≤35 mm) and the dose to the ipsilateral masseter muscle (iMM) and ipsilateral medial pterygoid muscle (iMPM). METHODS: Pretreatment and post-treatment measurement of MIO at 13 weeks revealed 17% of trismus cases in 83 patients treated with chemoradiation and intensity-modulated radiation therapy. Logistic regression models were fitted with dose parameters of the iMM and iMPM and baseline MIO (bMIO). A risk classification tree was generated to obtain optimal cut-off values and risk groups. RESULTS: Dose levels of iMM and iMPM were highly correlated due to proximity. Both iMPM and iMM dose parameters were predictive for trismus, especially mean dose and intermediate dose volume parameters. Adding bMIO, significantly improved Normal Tissue Complication Probability (NTCP) models. Optimal cutoffs were 58 Gy (mean dose iMPM), 22 Gy (mean dose iMM) and 46 mm (bMIO). CONCLUSIONS: Both iMPM and iMM doses, as well as bMIO, are clinically relevant parameters for trismus prediction.

SPECT/CT-guided elective nodal irradiation for head and neck cancer: Estimation of clinical benefits using NTCP models.

BACKGROUND AND PURPOSE: The great majority of patients with lateralized head and neck squamous cell carcinoma (HNSCC) treated with radiotherapy routinely undergo bilateral elective nodal irradiation (ENI), even though the incidence of contralateral regional failure after unilateral ENI is low. Excluding the contralateral neck from elective irradiation could reduce radiation-related toxicity and improve quality-of-life. The current study investigated the dosimetric benefits of a novel approach using lymph drainage mapping by SPECT/CT to select patients for unilateral ENI. PATIENTS AND METHODS: Forty patients with lateralized cT1-3N0-2bM0 HNSCC underwent lymph drainage mapping. Two radiation plans were made; the real plan with which patients were actually treated (selective SPECT/CT-guided plan irradiating the ipsilateral neck ±â€¯any contralateral draining level); and the virtual plan (standard plan according to institutional guidelines, as if the same patient would have been treated bilaterally). Radiation doses to clinically important organs-at-risk were compared between the two plans. We used five normal tissue complication probability (NTCP) models to predict the clinical benefits of this approach. RESULTS: Median dose reductions to the contralateral parotid gland, contralateral submandibular gland, glottic larynx, supraglottic larynx, constrictor muscle and thyroid gland were 19.2, 27.3, 11.4, 9.7, 12.1 and 18.4 Gy, respectively. Median NTCP reductions for xerostomia, contralateral parotid function, dysphagia, hypothyroidism and laryngeal edema were 20%, 14%, 10%, 20% and 5% respectively. CONCLUSIONS: Selective SPECT/CT-guided ENI results in significant dose reductions to various organs-at-risk and corresponding NTCP values, and will subsequently reduce the incidence and severity of different troublesome radiation-related toxicities and improve quality-of-life.

RapidArc, SmartArc and TomoHD compared with classical step and shoot and sliding window intensity modulated radiotherapy in an oropharyngeal cancer treatment plan comparison.

BACKGROUND: Radiotherapy techniques have evolved rapidly over the last decade with the introduction of Intensity Modulated RadioTherapy (IMRT) in different forms. It is not clear which of the IMRT techniques is superior in the treatment of head and neck cancer patients in terms of coverage of the planning target volumes (PTVs), sparing the organs at risk (OARs), dose to the normal tissue, number of monitor units needed and delivery time.The present paper aims to compare Step and Shoot (SS) IMRT, Sliding Window (SW) IMRT, RapidArc (RA) planned with Eclipse, Elekta VMAT planned with SmartArc (SA) and helical TomoHD™ (HT). METHODS: Target volumes and organs at risk (OARs) of five patients with oropharyngeal cancer were delineated on contrast enhanced CT-scans, then treatment plans were generated on five different IMRT systems. In 32 fractions, 69.12 Gy and 56 Gy were planned to the therapeutic and prophylactic PTVs, respectively. For the PTVs and 26 OARs ICRU 83 reporting guidelines were followed. Differences in the studied parameters between treatment planning systems were analysed using repeated measures ANOVA. RESULTS: Mean Homogeneity Index of PTV(therapeutic) is better with HT(.06) followed by SA(.08), RA(.10), SW(.10) and SS(.11). PTV(prophylactic) is most homogeneous with RA. Parotid glands prescribed mean doses are only obtained by SA and HT, 20.6 Gy and 21.7 Gy for the contralateral and 25.6 Gy and 24.1 Gy for the ipsilateral, against 25.6 Gy and 32.0 Gy for RA, 26.4 Gy and 34.6 Gy for SW, and 28.2 Gy and 34.0 Gy for SS. RA uses the least monitor units, HT the most. Treatment times are 3.05 min for RA, and 5.9 min for SA and HT. CONCLUSIONS: In the treatment of oropharyngeal cancer, we consider rotational IMRT techniques preferable to fixed gantry techniques due to faster fraction delivery and better sparing of OARs without a higher integral dose. TomoHD gives most homogeneous target coverage with more sparing of spinal cord, brainstem, parotids and the lower swallowing apparatus than most of the other systems. Between RA and SA, SA gives a more homogeneous PTV(therapeutic) while sparing the parotids more, but the delivery of RA is twice as fast with less overdose to the PTV(elective).

A practical technique to avoid the hippocampus in prophylactic cranial irradiation for lung cancer.

A practical technique is presented to deliver hippocampus avoiding prophylactic cranial irradiation for lung cancer patients, using two lateral fields. For a prescribed dose of 12×2.5 Gy, sparing of the hippocampi to 6.1 Gy was achieved with a V95% of the brain of 81.7%.

Risk factors for hearing loss in patients treated with intensity-modulated radiotherapy for head-and-neck tumors.

PURPOSE: Radiotherapy (RT) is a common treatment of head-and-neck carcinoma. The objective of this study was to perform a prospective multivariate assessment of the dose-effect relationship between intensity-modulated RT and hearing loss. METHODS AND MATERIALS: Pure tone audiometry at 0.250-16 kHz was obtained before and after treatment in 101 patients (202 ears). All patients received full-course intensity-modulated RT (range, 56-70 Gy), with a median cochlear dose of 11.4 Gy (range, 0.2-69.7). RESULTS: Audiometry was performed 1 week before and a median of 9 weeks (range, 1-112) after treatment. The mean hearing deterioration at pure tone average air-conduction 1-2-4 kHz was small (from 28.6 dB HL to 30.1 dB HL). However, individual patients showed clinically significant hearing loss, with 10-dB threshold shift incidences of 13% and 18% at pure tone averages air-conduction 1-2-4 kHz and 8-10-12.5 kHz, respectively. Post-treatment hearing capability was unfavorable in the case of greater inner ear radiation doses (p <0.0001), unfavorable baseline hearing capability (p <0.0001), green-eyed patients (p <0.0001), and older age (p <0.0001). Using multivariate analysis, a prediction of individual hearing capabiltity after treatment was made. CONCLUSION: RT-induced hearing loss in the mean population is modest. However, clinically significant hearing loss was observed in older patients with green eyes and unfavorable pretreatment hearing. In these patients, the intended radiation dose may be adjusted according to the proposed predictive model, aiming to decrease the risk of ototoxicity.