Clinical experiences with online adaptive radiotherapy of vulvar carcinoma.

BACKGROUND AND PURPOSE: Radiotherapy for vulvar carcinoma is challenging due to relatively high risk of locoregional disease recurrence, a technically challenging target, and postoperative lymphocele, and a high risk radiation sequelae. We aim to explore, if it is possible to reduce dose to normal tissue, while maintaining CTV coverage for this patient group with online adaptive radiotherapy. MATERIALS AND METHODS: 20 patients with vulvar carcinoma (527 fractions) were treated with online adaptation on a Varian Ethos accelerator. Setup CBCTs were acquired daily for adaptive planning. Verification CBCTs were acquired immediately prior to dose delivery. CTV dose coverage and dose to bladder and rectum were extracted from the scheduled and adapted plans as well as from adapted plans recalculated based on verification CBCTs. In addition, analysis of the decision of the adaptive procedure was performed for 17 patients (465 fractions). RESULTS: Mean CTV D95% and standard deviation was 98% ± 5% for the scheduled plan compared to 100.0 ± 0.3% and 100.0 ± 0.8% for the adapted plan on the setup and verification CBCT respectively. Dose to OARs varied substantially and did not show any benefit from adaption itself, however a margin reduction was implemented after the first patients treated. The adapted plan was chosen for 63.5% of the fractions and dominant reasons for not adapting were 'no significant dosimetric gain' (75 fractions, 14%) and 'Medical doctor (MD) not available for treatment' (50 fractions, 9.5%). The median adaption time was 15 min and the 25th and 75th percentile was 12 and 17 min, respectively. CONCLUSION: CTVs and PTVs dose coverage were significantly improved with adaptation compared to image-guided RT. This gain was robust during the treatment time.

Treatment planning for patients with low rectal cancer in a multicenter prospective organ preservation study.

BACKGROUND: Non-surgical management of rectal cancer relies on (chemo)radiotherapy as the definitive treatment modality. This study reports and evaluates the clinical high dose radiotherapy treatment plans delivered to patients with low resectable rectal cancer in a Danish multicenter trial. METHODS: The Danish prospective multicenter phase II Watchful Waiting 2 trial (NCT02438839) investigated definitive chemoradiation for non-surgical management of low rectal cancer. Three Danish centers participated in the trial and committed to protocol-specified treatment planning and delivery requirements. The protocol specified a dose of 50.4 Gy in 28 fractions to the elective volume (CTV-/PTV-E) and a concomitant boost of 62 Gy in 28 fractions to the primary target volume (CTV-/PTV-T). RESULTS: The trial included 108 patients, of which 106 treatment plans were available for retrospective analysis. Dose coverage planning goals for the main target structures were fulfilled for 94% of the treatment plans. However, large intercenter differences in doses to organs-at-risk (OARs) were seen, especially for the intestines. Five patients had a V60Gy>10 cm3 for the intestines and two patients for the bladder. CONCLUSION: Prescribed planning goals for target coverage were fulfilled for 94% of the treatment plans, however analysis of OAR doses and volumes indicated intercenter variations. Dose escalation to 62 Gy (as a concomitant boost to the primary tumor) introduced no substantial high dose volumes (>60 Gy) to the bladder and intestines. The treatment planning goals may be used for future prospective evaluation of highdose radiotherapy for organ preservation for low rectal cancer.

Implementing RapidArc into clinical routine: a comprehensive program from machine QA to TPS validation and patient QA.

PURPOSE: With the increased commercial availability of intensity modulated arc therapy (IMAT) comes the need for comprehensive QA programs, covering the different aspects of this newly available technology. This manuscript proposes such a program for the RapidArc (RA) (Varian Medical Systems, Palo Alto) IMAT solution. METHODS: The program was developed and tested out for a Millennium120 MLC on iX Clinacs and a HighDefinition MLC on a Novalis TX, using a variety of measurement equipment including Gafchromic film, 2D ion chamber arrays (Seven29 and StarCheck, PTW, Freiburg, Germany) with inclinometer and Octavius phantom, the Delta4 systam (ScandiDos, Uppsala, Sweden) and the portal imager (EPID). First, a number of complementary machine QA tests were developed to monitor the correct interplay between the accelerating/decelerating gantry, the variable dose rate and the MLC position, straining the delivery to the maximum allowed limits. Second, a systematic approach to the validation of the dose calculation for RA was adopted, starting with static gantry and RA specific static MLC shapes and gradually moving to dynamic gantry, dynamic MLC shapes. RA plans were then optimized on a series of artificial structures created within the homogeneous Octavius phantom and within a heterogeneous lung phantom. These served the double purpose of testing the behavior of the optimization algorithm (PRO) as well as the precision of the forward dose calculation. Finally, patient QA on a series of clinical cases was performed with different methods. In addition to the well established in-phantom QA, we evaluated the portal dosimetry solution within the Varian approach. RESULTS: For routine machine QA, the "Snooker Cue" test on the EPID proved to be the most sensitive to overall problem detection. It is also the most practical one. The "Twinkle" and "Sunrise" tests were useful to obtain well differentiated information on the individual treatment delivery components. The AAA8.9 dose calculations showed excellent agreement with all corresponding measurements, except in areas where the 2.5 mm fixed fluence resolution was insufficient to accurately model the tongue and groove effect or the dose through nearly closed opposing leafs. Such cases benefited from the increased fluence resolution in AAA10.0. In the clinical RA fields, these effects were smeared out spatially and the impact of the fluence resolution was considerably less pronounced. The RA plans on the artificial structure sets demonstrated some interesting characteristics of the PRO8.9 optimizer, such as a sometimes unexpected dependence on the collimator rotation and a suboptimal coverage of targets within lung tissue. Although the portal dosimetry was successfully validated, we are reluctant to use it as a sole means of patient QA as long as no gantry angle information is embedded. CONCLUSIONS: The all-in validation program allows a systematic approach in monitoring the different levels of RA treatments. With the systematic approach comes a better understanding of both the capabilities and the limits of the used solution. The program can be useful for implementation, but also for the validation of major upgrades.

Comparative renal, hepatic, and bone marrow toxicity of Cisplatin and radioactive Cisplatin (191Pt) in Wistar rats.

The aim of the study was to investigate the possibility to increase the therapeutic gain of the cytotoxic agent, cisplatin, by incorporation of radioactive platinum. In this study, we investigated how organs at risk (i.e., kidneys, bone marrow, and liver) are affected by treatment with 191Pt-cisplatin, compared to treatment with conventional cisplatin. Rats (total, n = 69) were divided into three groups and given 5 mg/kg 191Pt-cisplatin and 5 mg/kg nonradioactive cisplatin or saline. The weight of the animals and blood samples, including analysis of creatinine, bilirubin, alanine and aspartate aminotransferases and platelet count, was followed for 6 weeks after treatment. Histopathology examinations of kidney and liver tissues were performed. An initial decrease in weight gain was seen from 3 days after treatment with cisplatin and 191Pt-cisplatin and for 1 week onward; thereafter, the weight gain continued, following the same pattern as for the control group. Concentration of plasma creatinine was increased for both cisplatin groups but with no significant difference between treatment groups. No other significant differences in effect parameters were found. There was no increase in toxicity for radioactive cisplatin on liver, kidneys, and bone marrow, compared to conventional cisplatin. Further experimental and clinical studies on preparations of this type are thus warranted.

Incorrect dosimetric leaf separation in IMRT and VMAT treatment planning: Clinical impact and correlation with pretreatment quality assurance.

PURPOSE: Dynamic treatment planning algorithms use a dosimetric leaf separation (DLS) parameter to model the multi-leaf collimator (MLC) characteristics. Here, we quantify the dosimetric impact of an incorrect DLS parameter and investigate whether common pretreatment quality assurance (QA) methods can detect this effect. METHODS: 16 treatment plans with intensity modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) technique for multiple treatment sites were calculated with a correct and incorrect setting of the DLS, corresponding to a MLC gap difference of 0.5mm. Pretreatment verification QA was performed with a bi-planar diode array phantom and the electronic portal imaging device (EPID). Measurements were compared to the correct and incorrect planned doses using gamma evaluation with both global (G) and local (L) normalization. Correlation, specificity and sensitivity between the dose volume histogram (DVH) points for the planning target volume (PTV) and the gamma passing rates were calculated. RESULTS: The change in PTV and organs at risk DVH parameters were 0.4-4.1%. Good correlation (>0.83) between the PTVmean dose deviation and measured gamma passing rates was observed. Optimal gamma settings with 3%L/3mm (per beam and composite plan) and 3%G/2mm (composite plan) for the diode array phantom and 2%G/2mm (composite plan) for the EPID system were found. Global normalization and per beam ROC analysis of the diode array phantom showed an area under the curve <0.6. CONCLUSIONS: A DLS error can worsen pretreatment QA using gamma analysis with reasonable credibility for the composite plan. A low detectability was demonstrated for a 3%G/3mm per beam gamma setting.

Children with autism spectrum disorders who do not develop phrase speech in the preschool years.

There is uncertainty about the proportion of children with autism spectrum disorders who do not develop phrase speech during the preschool years. The main purpose of this study was to examine this ratio in a population-based community sample of children. The cohort consisted of 165 children (141 boys, 24 girls) with autism spectrum disorders aged 4-6 years followed longitudinally over 2 years during which time they had received intervention at a specialized autism center. In this study, data collected at the 2-year follow-up were used. Three categories of expressive language were defined: nonverbal, minimally verbal, and phrase speech. Data from the Vineland Adaptive Behavior Scales-II were used to classify expressive language. A secondary objective of the study was to analyze factors that might be linked to verbal ability, namely, child age, cognitive level, autism subtype and severity of core autism symptoms, developmental regression, epilepsy or other medical conditions, and intensity of intervention. The proportion of children who met the criteria for nonverbal, minimally verbal, and phrase speech were 15%, 10%, and 75%, respectively. The single most important factor linked to expressive language was the child's cognitive level, and all children classified as being nonverbal or minimally verbal had intellectual disability.