Reproducibility of the MRI-defined spinal cord position in stereotactic radiotherapy for spinal oligometastases

PurposeTo establish the reproducibility of the MRI-defined spinal cord position within the spinal canal.Materials and methodsWe acquired T1- and T2-weighted MRI scans of 15 volunteers on spine levels C7, T8 or L2. The scan protocol was repeated several times for different postures and time intervals. We determined the spinal cord shift (LR, AP, CC) using a rigid, grey value, vertebral body registration, followed by a spinal cord registration. We tested the sensitivity of our method, introducing artificial spinal cord shifts by varying the size and direction of the water-fat-shift (WFS) of the MR sequences.ResultsThe spinal cord position on MRI is reproducible within approximately 0.2 mm SD (LR, AP) and 0.7 mm SD (CC) when reproducing the posture on the same day, as well as several weeks later. However, when comparing different postures, shifts of ∼1.5 mm were found.Varying the WFS difference between scans (0.6–3.0 mm) induced equivalent virtual spinal cord shifts (0.5–2.5 mm).ConclusionsDisplacement of the spinal cord inside the spinal canal may occur as a result of posture change. Considering the total geometric accuracy of spine SBRT, MRI-defined spinal cord position is sufficiently reproducible and requires no addition to the typical setup-and-intrafraction motion PRV margin if posture is identical throughout the RT process.     

Myths,facts and scope of spinal cord tolerance dose revision in Intensity modulated SIB treatment of locally advanced head and neck cancer: A dosimetrical and radiobiological demonstration

PurposeTo explore the possibility of revising the spinal cord tolerance dose in Simultaneously Integrated Boost (SIB) intensity modulated treatment plan of locally advanced head and neck (H&N) cancer and assessment of achieved planning gain due to the revision. In SIB regimen, the Organ at Risk (OARs) tolerance dose is equally distributed throughout the treatment. Clinicians have usually considered the spinal cord tolerance to be the same as in conventional technique. However, in SIB fractionation regimen with intensity modulation treatment, the spinal cord may receive a physical dose of 45 Gy, with much lesser dose per fraction than 2 Gy per fraction. So when the dose of spinal cord is distributed throughout the treatment, the tolerance dose limit of physical dose can be considered higher than the usual conventional dose limits. In this study, an attempt has been made to explore the possibilities of dose escalation and treatment planning benefits while exploiting this “Window of Opportunity (WoO)” of increase in spinal cord and Planning Risk Volume (PRV) spinal cord tolerance dose.Material and methodsA total of 12 patients CT data set along with approved structure set of H&N cancer used for treatment planning in. Three independent SIB VMAT plans named as SPC, SPR and SPDE were generated for the 12 patients. First plan (SPC) was generated by considering standard spinal cord tissue constraint of maximum dose of 45 Gy and PRV spinal cord maximum dose 50 Gy as per QUANTEC summary and second plan (SPR) was generated considering spinal cord tissue constraint of maximum dose 52.50 Gy and PRV spinal cord maximum dose 56.35 Gy while optimization and dose calculation. The objectives for rest of the Organ at Risk (OAR) were kept same in both the plans during optimization and dose calculation. The SPC plan was copied for creation of third plan (SPDE) in which dose was escalated by increasing dose per fraction for target volumes such that dose to spinal cord reached a maximum dose of 52.50 Gy and PRV spinal cord maximum dose of 56.35 Gy. In this plan there have been changes to only dose per fraction, however dose optimization and dose calculation have not been performed. Radiobiological parameters TCP and NTCP were also calculated by using indigenously developed software.ResultsConsidering the increase of spinal cord tolerance dose as “window of opportunity”, a sufficient escalation in physical dose, Biological Effective Dose (BED) and Tumor Control Probability (TCP) was observed for all target volumes with acceptable level of NTCP values.ConclusionSufficient dose escalation and increased in TCP for target volumes or effective planning benefits can be achieved by revising the spinal cord tolerance dose in intensity modulated SIB treatment of locally advanced H&N cancers.     

Improved VMAT planning for head and neck tumors with an advanced optimization algorithm

ObjectiveIn this study, the “Progressive Resolution Optimizer PRO3“ (Varian Medical Systems) is compared to the previous version „PRO2“ with respect to its potential to improve dose sparing to the organs at risk (OAR) and dose coverage of the PTV for head and neck cancer patients.Materials and MethodsFor eight head and neck cancer patients, volumetric modulated arc therapy (VMAT) treatment plans were generated in this study. All cases have 2-3 phases and the total prescribed dose (PD) was 60-72 Gy in the PTV. The study is mainly focused on the phase 1 plans, which all have an identical PD of 54 Gy, and complex PTV structures with an overlap to the parotids. Optimization was performed based on planning objectives for the PTV according to ICRU83, and with minimal dose to spinal cord, and parotids outside PTV. In order to assess the quality of the optimization algorithms, an identical set of constraints was used for both, PRO2 and PRO3. The resulting treatment plans were investigated with respect to dose distribution based on the analysis of the dose volume histograms.ResultsFor the phase 1 plans (PD = 54 Gy) the near maximum dose D_2% of the spinal cord, could be minimized to 22±5 Gy with PRO3, as compared to 32±12 Gy with PRO2, averaged for all patients. The mean dose to the parotids was also lower in PRO3 plans compared to PRO2, but the differences were less pronounced. A PTV coverage of V_95% = 97±1% could be reached with PRO3, as compared to 86±5% with PRO2. In clinical routine, these PRO2 plans would require modifications to obtain better PTV coverage at the cost of higher OAR doses.ConclusionA comparison between PRO3 and PRO2 optimization algorithms was performed for eight head and neck cancer patients. In general, the quality of VMAT plans for head and neck patients are improved with PRO3 as compared to PRO2. The dose to OARs can be reduced significantly, especially for the spinal cord. These reductions are achieved with better PTV coverage as compared to PRO2. The improved spinal cord sparing offers new opportunities for all types of paraspinal tumors and for re-irradiation of recurrent tumors or second malignancies.     

Sarcomes d’Ewing localisés du rachis chez l’enfant : étude préliminaire d’escalade de dose comparant les techniques innovantes

PurposeAlthough radiosensitive, spinal locations of Ewing's sarcomas are challenging for the radiation oncologist due to poor radiation tolerance of the spinal cord. However, some favorable anatomical compartments – that may represent more than 20% – were associated with a better outcome and could benefit from a radiation dose escalation using the most recent radiation therapy techniques.Materials and methodsWe performed a dose escalation study on one patient, declined in two scenarios: (1) a tumour located within a single vertebral body and (2) a locally advanced disease involving the vertebral foramen and paraspinal soft tissues. Five dose-levels are proposed: 44.8 Gy, 54.4 Gy, 59.2 Gy, 65.6 Gy and 70.4 Gy (1.6 Gy per session, 8 Gy per week). The 3D-conformational technique is compared with static intensity modulated radiation therapy (IMRT), helical tomotherapy, volumetric modulated arc therapy (VMAT), stereotactic body robotic radiation therapy (SBRT) and protontherapy (passive scattering). Two constraints had to be respected in order to skip to the next level: the planned target volume (PTV) coverage must exceed 95% and the D_2% on the spinal cord shall not exceed a given constraint set at 50 Gy in case 1 and 44 Gy in case 2 due to initial neurological sufferance.ResultsOnly protontherapy, SBRT, helical tomotherapy and VMAT appear able to reach the last dose level while respecting the constraints in case 1. On the other hand, only helical tomotherapy seems capable of reaching 59.2 Gy on the PTV in case 2.ConclusionWith the most recent radiation therapy techniques, it becomes possible to deliver up to 70.4 Gy in a favorable compartment in this sham patient. Unfavorable compartments can receive up to 59.2 Gy. Definitive radiation therapy may be an interesting local treatment option to be validated in an early phase trial.     

Intensity-modulated Radiotherapy Allows Escalation of the Radiation Dose to the Pelvic Lymph Nodes in Patients with Locally Advanced Prostate Cancer: Preliminary Results of a Phase I Dose Escalation Study

AimPelvic irradiation in addition to prostate irradiation may improve outcome in locally advanced prostate cancer, but is associated with dose-limiting bowel toxicity. We report the preliminary results of a dose escalation study using intensity-modulated radiotherapy.Materials and methodsEligible patients had high-risk (T3, Gleason ≥8 or prostate-specific antigen ≥20 ng/ml) or lymph node-positive disease. Intensity-modulated radiotherapy was inverse planned giving 70 Gy/35 fractions to the prostate and 50 Gy/55 Gy/60 Gy in sequential cohorts to the pelvis with a 5 Gy boost to positive lymph nodes. Acute and late toxicity were recorded with Radiation Therapy Oncology Group (RTOG) and Late Effects Normal Tissue - Subjective Objective Management LENT-SOM scales. Neoadjuvant androgen suppression was given for 3 years. This report concerns the 50 and 55 Gy cohorts.ResultsSeventy-nine men were recruited (25 to 50 Gy/54 to 55 Gy) with a median follow-up of 2 years. Patients were divided into two groups according to the total bowel volume outlined (median 450 cm³). Acute RTOG (≥2) bowel toxicity was 40 and 50% for the 50 and 55 Gy groups and 38 and 51% for bowel volume <450 cm³ and ≥450 cm³, respectively, suggesting both volume and dose relationships for acute effects. Late RTOG diarrhoea ≥grade 2 was only seen with bowel volume ≥450 cm³, but no dose effect was apparent (12%/50 Gy and 10%/55 Gy). LENT-SOM bowel ≥grade 2 toxicity occurred in 22%/50 Gy and 15%/55 Gy. Only one patient had grade 3 toxicity. A dose volume histogram analysis showed increased late RTOG diarrhoea ≥grade 2 with larger bowel volume irradiated, significant for BV40 >124 cm³ (P = 0.04), BV45 >71 cm³ (P = 0.03) and BV60 >2 cm³ (P = 0.01).ConclusionsAcute and late bowel toxicity was acceptably low using a pelvic dose of up to 55 Gy over 7 weeks. Both relate to total pelvic bowel volume and dose volume constraints have been defined.     

Limites de la définition des contraintes de dose pour les organes à risque spécifiques à la radiothérapie stéréotaxique

Stereotactic radiotherapy is a very hypofractionated radiotherapy (> 7.5 Gy per fraction), and therefore is more likely to induce late toxicities than conventional normofractionated irradiations. The present study examines four frequent and potentially serious late toxicities: brain radionecrosis, radiation pneumonitis, radiation myelitis, and radiation-induced pelvic toxicities. The critical review focuses on the toxicity scales, the definition of the dose constrained volume, the dosimetric parameters, and the non-dosimetric risk factors. The most commonly used toxicity scales remain: RTOG/EORTC or common terminology criteria for adverse events (CTCAE). The definition of organ-at-risk volume requiring protection is often controversial, which limits the comparability of studies and the possibility of accurate dose constraints. Nevertheless, for the brain, whatever the indication (arteriovenous malformation, benign tumor, metastasis of solid tumors...), the association between the volume of brain receiving 12 Gy (V12 Gy) and the risk of cerebral radionecrosis is well established for both single and multi-fraction stereotactic irradiation. For the lung, the average dose received by both lungs and the V20 seem to correlate well with the risk of radiation-induced pneumonitis. For the spinal cord, the maximum dose is the most consensual parameter. Clinical trial protocols are useful for nonconsensual dose constraints. Non-dosimetric risk factors should be considered when validating the treatment plan.     

Different treatment planning protocols can lead to large differences in organ at risk sparing

Background and purposeDifferent planning protocols may define varying planning target volume (PTV) dose criteria. We investigated the hypothesis that this could result in differences in organ-at-risk (OAR) sparing.Material and methodsVolumetric modulated arc therapy plans were created for ten locally advanced head and neck cancer patients following PTV criteria specified by the RTOG, EORTC and institutional (VUmc) protocols. Resulting plans were evaluated on the basis of the homogeneity index, calculated for the boost/elective PTVs as HI_B/HI_E = 100% * (D2% − D98%)/D50% and mean dose to individual and composite salivary (comp_sal) and swallowing (comp_swal) OARs.ResultsRTOG plans were the most homogeneous, with mean HI_B of 8.2 ± 0.9%, compared to 9.5 ± 1.0%/11.6 ± 1.5% for the VUmc/EORTC plans. EORTC plans provided most OAR sparing, with comp_sal/comp_swal doses of 24.6 ± 7.7/22.9 ± 4.2 Gy, compared to 32.2 ± 9.7/29.9 ± 4.2 Gy and 28.4 ± 8.1/24.7 ± 5.3 Gy for RTOG and VUmc, respectively. EORTC provided 7.2/7.7 Gy mean dose reductions to the contra/ipsilateral parotid glands compared to RTOG.ConclusionsDifferent planning protocols resulted in different levels of PTV dose homogeneity. We observed differences of up to ⩾7 Gy in composite and individual mean OAR doses. This could influence rates of toxicity and should be taken into account when comparing clinical studies. A consensus should be reached between major trial groups on appropriate PTV parameters.     

Techniques classique bidimensionnelle et mono-isocentrique tridimensionnelle dans l’irradiation du sein et des aires ganglionnaires : comparaison dosimétrique

PurposeThe activity of our radiation oncology department mainly relies on breast pathology. Since July 2009, all the irradiations delivered simultaneously to the breast (CTV1), the surgical bed (CTV2), the internal mammary chain and the supra- and infraclavicular areas have been carried out using a mono-isocentric technique. This study aimed to compare dosimetric results between conventional 2D and mono-isocentric 3D techniques with or without optimization.Patients and methodsFrom January to August 2009, 20 patients with breast cancer in whom irradiation of the CTV1, CTV2, internal mammary chain and supra- and infraclavicular areas was retained, were included in a specific cohort. In each case, we have compared dosimetric results obtained with the conventional technique and with a mono-isocentric 3D technique, either with manual field in the field segmentation or with automatic segmentation (Oncentra Masterplan^® from Nucletron^®, Optimizer^® solution). Selected criteria were as follows: V95, V107 and mean dose (Dmean) to the target volumes, V20 and V30 to the ipsilateral lung, V35 and mean dose to the heart and maximal dose (Dmax) to the spinal cord.ResultsSupra- and infraclavicular areas irradiation was significantly better using the mono-isocentric 3D technique (V95 %: 89.7 % vs. 77.1 %; P = 0.001) as well as dose homogeneity (Dmean: 46.3 Gy vs. 45.1 Gy; P = 0.008). No statistical difference was observed for the other target volumes. Heart and spinal cord protection were better with the mono-isocentric 3D technique (respectively Dmean: 8.4 Gy vs. 11.1 Gy; P < 0.0001 and Dmax: 29.2 Gy vs. 35.8 Gy; P = 0.0003).ConclusionMono-isocentric irradiation of the breast and lymphatic areas is a modern technique that benefits from imaging and computer progresses while being simple to carry out using standard planning system and linear accelerators. Mono-isocentric 3D irradiation with manual segmentation of the breast and the nodal areas provides a target volume irradiation comparing with conventional technique 2D and a better protection of the heart and of the spinal cord.     

Dosimetric analytic comparison of inverse and forward planned IMRT techniques in the treatment of head and neck cancer

PurposeOur aim was to investigate if, and to what degree, improvements of IMRT treatment plans generated by forward planning can be achieved with an inverse planning strategy for treatments of head and neck cancer.MethodsBetween June 2007 and April 2008, 19 patients with head-and-neck cancers were treated at KAAH and Oncology Center Jeddah, using forward planning intensity modulated radiation therapy (FP-IMRT). They received thirty fractions over six weeks, to simultaneously deliver 66 Gy to the gross tumor (CTV1), 60 Gy to the soft tissue and nodes adjacent to the previous volume (CTV2), and 54 Gy to elective nodes (CTV3). These are biologically equivalent to 70, 60, and 50 Gy, if given 2 Gy per fraction.These were retrospectively re-planned with an inverse planning algorithm (IP-IMRT). The main objective of the optimization process was sparing of the parotid glands, spinal cord, and brainstem beside adequate treatment of the planning target volume.ResultsHaving 95% and 98% of CTV1 to receive at least 95% and 90% of prescribed dose respectively was fulfilled in all cases in both groups with higher figures in group B (IP-IMRT) than in group A (FR-IMRT), more obvious in CTV2 and CTV3. The average maximum dose to the spinal cord was 45.1 Gy in group A, and 41.6 Gy in group B. The mean dose of both parotid glands was kept below 26 Gy in four patients in group A, but in all cases in group B.ConclusionIP-IMRT selectively spared critical organs to greater degree with better target coverage and should be considered the standard of treatment in head and neck tumors.     

Local control and sequelae in localised Ewing tumours of the spine: A French retrospective study

ObjectivesTo evaluate both local outcome and sequelae of non-metastatic spinal Ewing tumours (EWT).Patients and methodsA French cohort of patients ?50 years with localised spinal EWT treated between 1988 and 2009, was analysed in regard to tumour characteristics (e.g. volume, vertebral compartment, spinal cord compression, paraspinal soft tissue invasion), local treatment modalities (surgery (S) and margin quality, radiotherapy (RT) dose), response to treatment (e.g. histological response to neoadjuvant chemotherapy (CT)), tumour local control (LC) and sequelae.ResultsSeventy-five patients treated in successive trials were evaluated for LC: SFOP-EW88 (n = 14), SFOP-EW93 (n = 17) and EuroEwing99 (n = 44). Fifty-seven patients (79%) presented initial neurological compression and 69% had inaugural decompressive S. Local treatment modality was S + RT (n = 50), RT alone (n = 19) and S alone (n = 6). Surgery was mainly intralesional (66%). Local recurrences had occurred in 19 patients (14 local, 5 loco-regional) with a median interval of 25 months (1–50). After a 7 year median follow-up (1–22 years), the 5-year LC, relapse-free survival (RFS) and overall survival (OS) reached 78.0% (95%CI: 62.6–84.6), 57.0% (95%CI: 45.2–68.9) and 70.0% (95%CI: 59.1–81.0), respectively. Vertebral compartment involved was the only prognostic factor (5-year LC rate 100% versus 71% for favourable and unfavourable compartment, p < 0.03). Among 41 five-year survivors, we observed spinal curvature deformation (35%), growth retardation (28%), spinal reduction mobility (40%), spinal pain (25%) and neurological sequelae (32%) without any significant association with a particular local procedure.ConclusionRT is the backbone of a successful local treatment of spinal EWT. The place of S remains a pending question. Its actual benefit will likely evolve with new available RT techniques.     

Can we predict the cardiac benefit of deep inspiration breath hold for left breast and regional nodal irradiation?

PurposeDeep inspiration breath hold (DIBH) is used to decrease the dose of radiotherapy delivered to the heart. There is a need to define criteria to select patients with the potential to derive a real clinical benefit from DIBH treatment. Our study's main goal was to investigate whether two CT-scan cardiac anatomical parameters, cardiac contact distance in the parasagittal plane (CCDps) and lateral heart-to-chest distance (HCD), were predictive of unmet dosimetric cardiac constraints for left breast and regional nodal irradiation (RNI).Materials and methodsThis retrospective single-institution dosimetric study included 62 planning CT scans of women with left-sided breast cancer (BC) from 2016 to 2021. Two independent radiation oncologists measured HCD and CCDps twice to assess inter- and intra-observer reproducibility. Dosimetric constraints to be respected were defined, and dosimetric parameters of interest were collected for each patient.ResultsMean heart dose was 7.9 Gy. Inter-rater reproducibility between the two readers was considered excellent. The mean heart dose constraint < 8 Gy was not achieved in 25 patients (40%) and was achieved in 37 patients (60%). There was a significant correlation between mean heart dose and HCD (r_s = –0.25, P = 0.050) and between mean heart dose and CCDps (r_s = 0.25, P = 0.047). The correlation between HCD and CCDps and unmet cardiac dosimetric constraints was not statistically significant.ConclusionOur dosimetric analysis did not find that the cardiac anatomical parameters HCD and CCDps were predictive of unmet dosimetric cardiac constraints, nor that they were good predictors for cardiac exposure in left-sided BC radiotherapy comprising RNI.     

Clinical outcome after CyberKnife® radiosurgery re-irradiation for recurrent brain metastases

PurposeThe objective of this study was to elucidate the impact on clinical outcomes resulting from re-irradiation for locally recurrent (LR) brain metastases (BM) using CyberKnife® stereotactic radiosurgery (SRS).Materials and methodsSeventy-seven patients with 254 LR BM lesions treated using SRS re-irradiation between January 2014 and December 2018 were analysed in this retrospective study. The local control (LC), overall survival (OS) rates, and adverse events were assessed. The adverse events were classified according to the Common terminology for adverse event (CTCAE) v5.0.ResultsThe median follow-up duration was 8.9 months. The median age of the patients was 55 years (IQR: 47–62). The 3, 6, and 9-month LC and OS rates were 92.2%, 73.4%, and 73.4% and 79.2%, 61.0%, and 48.1%, respectively. On multivariate analysis the gender (male vs. female; HR, 1.79; 95% CI, 1.06–3.01; P = 0.028), type of first brain radiation (WBI vs. SRS) followed by re-irradiation using SRS (HR, 9.32; 95% CI, 2.77–15.27; P < 0.001) tumour volume (> 12cc vs. ≤ 12cc; HR, 1.84; 95% CI, 1.10–3.11; P = 0.02), and recursive partitioning analysis (RPA) (I vs. II & III; HR, 0.38; 95% CI, 0.19–0.70; P = 0.001) were independent predictive factor for OS. Radionecrosis was reported in 3 patients.ConclusionWith acceptable toxicity, SRS re-irradiation for LR BM showed a favourable rate for LC and OS and reported better OS for the female gender, a patient undergoing first brain radiation with SRS, tumour volume ≤ 12cc, and RPA-I. This result needs to be further evaluated in future clinical studies.     

3D printing for dosimetric optimization and quality assurance in small animal irradiations using megavoltage X-rays

PurposeNew therapeutic options in radiotherapy (RT) are often explored in preclinical in-vivo studies using small animals. We report here on the feasibility of modern megavoltage (MV) linear accelerator (LINAC)-based RT for small animals using easy-to-use consumer 3D printing technology for dosimetric optimization and quality assurance (QA).MethodsIn this study we aimed to deliver 5 × 2 Gy to the half-brain of a rat using a 4 MV direct hemi-field X-ray beam. To avoid the beam's build-up in the target and optimize dosimetry, a 1 cm thick, customized, 3D-printed bolus was used. A 1:1 scale copy of the rat was 3D printed based on the CT dataset as an end-to-end QA tool. The plan robustness to HU changes was verified. Thermoluminescent dosimeters (TLDs), for both MV irradiations and for kV imaging doses, and a gafchromic film were placed within the phantom for dose delivery verifications. The phantom was designed using a standard treatment planning software, and was irradiated at the LINAC with the target aligned using kV on-board imaging.ResultsThe plan was robust (dose difference < 1% for HU modification from 0 to 250). Film dosimetry showed a good concordance between planned and measured dose, with the steep dose gradient at the edge of the hemi-field properly aligned to spare the contralateral half-brain. In the treated region, the mean TLDs percentage dose differences (±2 SD) were 1.3% (±3.8%) and 0.9% (±1.7%) beneath the bolus. The mean (±2 SD) out-of-field dose measurements was 0.05 Gy (±0.02 Gy) for an expected dose of 0.04 Gy. Imaging doses (2 mGy) still spared the contralateral-brain.ConclusionsUse of consumer 3D-printers enables dosimetry optimization and QA assessment for small animals MV RT in preclinical studies using standard LINACS.     

Calcifications intraprostatiques : marqueurs fiduciels naturels dans la radiothérapie guidée par l’image du cancer de la prostate

PurposeTo establish whether intraprostatic calcifications can serve as natural fiducials for image-guided radiotherapy (IGRT), replacing the implantation of intraprostatic fiducial markers.Patients and methodsPatients with prostate cancer, having intraprostatic calcifications visible on CT scan were selected and underwent intensity-modulated radiotherapy/3D conformal radiotherapy with IGRT in the department of radiotherapy of Henri-Mondor Hospital. All cone-beam computed tomographies (CBCT) were repositioned on intraprostatic calcifications. For each acquired image, displacements of intraprostatic calcifications were calculated with reference to position on planning CT in three directions: lateral, longitudinal and vertical.ResultsBetween 2011 and 2013, nine patients had 183 CBCT. For each image, three displacements and space coordinates were calculated using a single reference (intraprostatic calcification). Mean lateral, longitudinal and vertical movements were 0.26 ± 5.7 mm, −1 ± 4.6 mm and 0.42 ± 3.5 mm, respectively.ConclusionStudies exploring prostatic movements with fiducial markers as reference and ours with natural fiducials yield similar results. Our data confirm previous studies that have suggested that intraprostatic calcifications can be used as natural fiducials with potential reduction of iatrogenic risks and costs associated with the implantation of fiducial markers.     

Late toxicity after intensity modulated and image guided radiation therapy for localized prostate cancer and post-prostatectomy patients

PurposeTo examine late gastrointestinal (GI) and genitourinary (GU) toxicity profiles of patients treated for prostate cancer either definitively or post-prostatectomy with both intensity modulated radiation therapy (IMRT) and image guided radiation therapy (IGRT).Methods and MaterialsA total of 333 patients treated definitively and 104 patients treated postoperatively with IMRT and varying IGRT techniques were retrospectively examined to evaluate GI and GU toxicity profiles > 1 year from treatment. Available dosimetric data were used for correlative analysis.ResultsThe median follow-up time for the definitive patients was 41 months and the median follow-up time for the post-prostatectomy patients was 33 months. No late grade 4 or 5 GI or GU toxicities were observed. For definitive patients, the rates of grade ≥ 2 GI and GU toxicity at 3 years were 4.9% and 4.5%, respectively. In the postoperative cohort the rate of grade > 2 GU toxicity was 11.6%, with no grade ≥ 2 GI toxicity. In the definitive cohort's Cox proportional hazards regression univariate analysis, use of anticoagulation was significantly associated with GI toxicity and age, bladder V50 and IGRT modality were associated with GU toxicity, and only age remained significant in the multivariate model. In univariate analysis for the postoperative cohort, no dosimetric value correlated with GU toxicity, nor did age or time from radical prostatectomy to radiation.ConclusionsIMRT with IGRT achieved low rates of GI and GU toxicity in the definitive and postoperative setting.     

Adaptive radiation therapy: When,how and what are the benefits that literature provides?

PurposeTo identify from the current literature when is the right time to replan and to assign thresholds for the optimum process of replanning. Nowadays, adaptive radiotherapy (ART) for head and neck cancer plays an exceptional role consisting of an evaluation procedure of the prominent anatomical and dosimetric variations. By performing complex radiotherapy methods, the credibility of the therapeutic result is crucial. Image guided radiotherapy (IGRT) was developed to ensure locoregional control and thus changes that might occur during radiotherapy be dealt with.Materials and methodsAn electronic research of articles published in PubMed/MEDLINE and Science Direct databases from January 2004 to October 2020 was performed. Among a total of 127 studies assessed for eligibility, 85 articles were ultimately retained for the review.ResultsThe most noticeable changes have been reported in the middle fraction of the treatment. Therefore, the suggested optimal time to replan is between the third and the fourth week. Anatomical deviations > 1 cm in the external contour, average weight loss > 10%, violation in the dose coverage of the targets > 5%, and violation in the dose of the peripherals were some of the thresholds that are currently used, and which lead to replanning.ConclusionART may decrease toxicity and improve local-control. Whether it is beneficial or not, depends ultimately on each patient. However, more investigation of the changes should be performed in future prospective studies to obtain more accurate results.     

Evaluation of the safety of C-1311 (SYMADEX) administered in a phase 1 dose escalation trial as a weekly infusion for 3 consecutive weeks in patients with advanced solid tumours

PurposeC-1311 is a member of the novel imidazoacridinone family of anticancer agents. This phase 1 trial was designed to investigate the safety, tolerability and preliminary anti-tumour activity of C-1311.Patients and methodsThis was a phase 1, inter-subject dose escalating and pharmacokinetic study of intravenous (IV) C-1311, administered weekly during 3 consecutive weeks followed by 1 week rest (constituting 1 cycle) in subjects with advanced solid tumours.ResultsTwenty-two (22) patients were treated with C-1311, the highest dose given was 640 mg/m². All subjects experienced one or more treatment-related adverse events (AEs). The most frequently observed treatment-related AEs were neutropaenia and nausea (50% each), followed by vomiting (27%), anaemia (23%), asthenia (23%) and diarrhoea (18%). Most treatment-related AEs were of Common Terminology Criteria for Adverse Events (CTCAE) grades 1–2, except for the blood and lymphatic system disorders, which were primarily of grades 3–4. The recommended dose (RD) of C-1311 administered as once weekly IV infusions for 3 weeks every 4 weeks is 480 mg/m², with the dose limiting toxicity (DLT) being grade 4 neutropaenia lasting more than 7 days. Treatment at this dose offers a predictable safety profile and excellent tolerability.ConclusionThe safety profile and preliminary anti-tumour efficacy of C-1311, observed in this broad-phase dose-finding study, warrants further evaluation of the compound.     

Total body irradiation: Significant dose sparing of lung tissue achievable by helical tomotherapy

PurposeTotal body irradiation (TBI) is an important procedure in the conditioning for bone marrow and hematopoietic stem cell transplantation. Doses up to 12 Gy are delivered in hyperfractionated regimes. TBI performed with helical Tomotherapy® (Accuray, Madison, Wisconsin, USA) is an alternative to conventional techniques to deliver dose in extended target volumes with the possibility of simultaneous dose sparing to organs at risk. In this study we focused on maximum dose reduction to the lungs in TBI using helical Tomotherapy®.Material and methodsForty treatment plans of patients who received TBI were calculated with TomoH® (Accuray, Madison, Wisconsin, USA, Version 2.0.4) with a dose of 12 Gy delivered in six equal fractions (2 × 2 Gy/day). Planning iterations necessary to accomplish ICRU 83 report should be less than 250. Treatment time should be practicable in daily routine (<60 min.). Besides the usual contouring of organs at risk special contouring was required for optimization processes which focused on maximum dose sparing in the central lung tissue. Dose constraints (D2, D98, D99) were predefined for target volumes (i.e. PTV TBI D99: 90% of prescribed dose). Homogeneity index <0.15 was defined for acceptability of the treatment plan.ResultsFor all patients acceptable treatment plan fulfilling the predefined constraints were achievable. An average time of 46 min is required for treatment. Thirty-four of forty patients fulfilled D2 in the PTV TBI. Four patients failed D2 due to a high BMI >28 (maximum dose 13.76 Gy = 114.7%). The D98 in the PTV TBI was not reached by 2/40 patients due to BMI > 31 (minimum dose 11.31 Gy = dose coverage of 94.2%). Also these two patients failed the homogeneity index <0.15. The mean lung dose over all patients of the right lung was 7.18 Gy (range 6.4–9.5 Gy). The left lung showed a median (D50) dose of 7.9 Gy (range 6.7–9.3 Gy). Central lung dose showed a mean dose (D50) of 5.16 Gy (range 4.02–7.29 Gy). The D80 of the central lung showed an average dose of 3.87 Gy.ConclusionsTotal body irradiation using helical Tomotherapy® can be delivered with maximum lung tissue sparing (<6 Gy) but without compromise in adjacent PTV TBI structures (i.e. ribs, heart). High conformity and homogeneity in extended radiation volumes can be reached with this technique in an acceptable planning and treatment time. Limitations may occurred in patients with high body mass index.