Post-chemotherapy target volumes are safe as boost volume for intact breast radiotherapy in locally advanced breast cancer.

PURPOSE: The purpose of our study is to evaluate the challenges in identification of postoperative complexes (POC), the utility of clips in delineation of clinical target volume for boost in LABC downstaged with neoadjuvant chemotherapy (NACT) and to correlate this with patterns of recurrence. METHODS AND MATERIALS: LABC patients who underwent NACT followed by BCS and radiotherapy (2007-2014) were the subject of our analysis. The data on visibility and characteristics of postoperative cavity (POC), concordance of its volume with clip volume on radiation planning scan were retrieved. A 1 cm margin beyond POC was delineated as a clinical target volume (CTV). Postoperative whole breast and supraclavicular radiotherapy (50 Gy/25fractions/5wk or 42.4 Gy/16#/3 wk) followed by boost (10-16 Gy/5-8#/1-1.5wk) were delivered. Patterns of recurrence were evaluated. RESULTS: Out of 60 patients, 28.3% patients had stage II disease and 71.7% had stage III disease. 25% patients achieved pathological CR (complete response). The median POC volume was 30 cc and the median clip volume was 40 cc. The concordance of POC volume with clip volume was seen in 80%. Clips served as a good surrogate for POC in 80% of patients. At a median follow-up of 65 months (IQ range 32-84 months), and a lost to follow-up rate of 11.6 %, 3.3% (n = 2) patients had local recurrence (LR) and 8.3% (n = 5) had regional recurrence (LRR) in the supraclavicular region. CONCLUSIONS: Delineation of post NACT excision cavity as POC for boost radiotherapy is safe. Clips serve as a good surrogate for CTV delineation in 75% patients.

Comparison of biological-based and dose volume-based intensity-modulated radiotherapy plans generated using the same treatment planning system.

PURPOSE: Nowadays, most of the radiotherapy (RT) treatment planning systems (TPSs) uses dose or dose-volume (DV)-based cost functions for Intensity modulated radiation therapy (IMRT) fluence optimization. Recently, some of the TPSs incorporated biological-based cost function for IMRT optimization. Most of the previous studies compared IMRT plans optimized using biological-based and DV-based cost functions in two different TPSs. Hence, the purpose of the study is to compare equivalent uniform dose (EUD)-based and DV-based IMRT plans generated using the same TPS. MATERIALS AND METHODS: Twenty patients with prostate cancer were retrospectively selected for this study. For each patient, two IMRT plans were generated using EUD-based cost function (EUD_TP) and DV-based cost (DV_Treatment Plan (TP)), respectively. The generated IMRT plans were evaluated using both physical and biological dose evaluation indices. RESULTS: Biological-based plans ended up with a highly inhomogeneous target dose when compared to DV-based plans. For serial organs, Dnear-max or D2%(Gy) of EUD-based plans showed significant difference with DV-based plans (P = 0.003). For both rectum and bladder, there was a significant difference in mean dose and D30%(Gy) dose between EUD-based plans and DV-based plans. CONCLUSION: In this study, we decoupled the influence of optimization parameters from the potential use of EUD-based cost functions on plan quality by generating both plans in the same TPS.

Objective and subjective assessment of xerostomia in patients of locally advanced head-and-neck cancers treated by intensity-modulated radiotherapy.

BACKGROUND: Parotid-sparing intensity-modulated radiotherapy (IMRT) effectively reduces xerostomia in head-and-neck cancer (HNC). Changes in the salivary output at 1 year were studied and correlation with quality of life (QOL) changes in patients of locally advanced HNC (LAHNC) was drawn. MATERIALS AND METHODS: Between October 2009 and October 2011, 20 patients of LAHNC were treated with IMRT using simultaneous integrated boost technique. High-risk clinical target volume (CTV) was given a dose of 66 Gy/30 fr, intermediate-risk CTV 60 Gy/30 fr, and low-risk CTV 54 Gy/30 fr. The saliva flow rate was estimated for 5 min at rest (unstimulated) and after using lemon drops (stimulated) for the next 5 min, at baseline (pretreatment), and 3, 6, and 12 months following treatment. Evaluation of patients' perception of dry mouth was done using EORTC-QLQ-C30 and HN35 questionnaires at the same time points. RESULTS: Baseline unstimulated and stimulated salivary flow rates were 0.659 ml/min and 1.69 ml/min, respectively. At 3 months, a significant reduction in unstimulated (0.346 ml/min) and stimulated (0.80 ml/min) flow rate was observed. Unstimulated flow rate continued to decrease further till 6 months (0.295 ml/min), but slight improvement was seen in stimulated flow rate (0.91 ml/min). At 12 months, minimal recovery was observed in both unstimulated (0.362 ml/min) and stimulated flow rates (1.09 ml/min). EORTC-QOL questionnaire mean scores for dryness and stickiness of saliva were 10 and 15 at baseline and increased to 36 and 25, respectively, at 3 months. At 6 months, symptom score for dryness further increased to 45 and then decreased to 33 at 12 months. Stickiness score remained static from 3 to 12 months. Salivary flow rate correlated well with dry mouth (P < 0.05) but not with the perception of sticky saliva (P = 0.82) at 6 months and beyond. CONCLUSIONS: Both salivary flow rate and xerostomia-related questions worsened at 3 months even with IMRT and showed a similar pattern of recovery.

Investigating different computed tomography techniques for internal target volume definition.

PURPOSE: The aim of this work was to evaluate the various computed tomography (CT) techniques such as fast CT, slow CT, breath-hold (BH) CT, full-fan cone beam CT (FF-CBCT), half-fan CBCT (HF-CBCT), and average CT for delineation of internal target volume (ITV). In addition, these ITVs were compared against four-dimensional CT (4DCT) ITVs. MATERIALS AND METHODS: Three-dimensional target motion was simulated using dynamic thorax phantom with target insert of diameter 3 cm for ten respiration data. CT images were acquired using a commercially available multislice CT scanner, and the CBCT images were acquired using On-Board-Imager. Average CT was generated by averaging 10 phases of 4DCT. ITVs were delineated for each CT by contouring the volume of the target ball; 4DCT ITVs were generated by merging all 10 phases target volumes. Incase of BH-CT, ITV was derived by boolean of CT phases 0%, 50%, and fast CT target volumes. RESULTS: ITVs determined by all CT and CBCT scans were significantly smaller (P < 0.05) than the 4DCT ITV, whereas there was no significant difference between average CT and 4DCT ITVs (P = 0.17). Fast CT had the maximum deviation (-46.1% ± 20.9%) followed by slow CT (-34.3% ± 11.0%) and FF-CBCT scans (-26.3% ± 8.7%). However, HF-CBCT scans (-12.9% ± 4.4%) and BH-CT scans (-11.1% ± 8.5%) resulted in almost similar deviation. On the contrary, average CT had the least deviation (-4.7% ± 9.8%). CONCLUSIONS: When comparing with 4DCT, all the CT techniques underestimated ITV. In the absence of 4DCT, the HF-CBCT target volumes with appropriate margin may be a reasonable approach for defining the ITV.

Magnitude, Impact, and Management of Respiration-induced Target Motion in Radiotherapy Treatment: A Comprehensive Review.

Tumors in thoracic and upper abdomen regions such as lungs, liver, pancreas, esophagus, and breast move due to respiration. Respiration-induced motion introduces uncertainties in radiotherapy treatments of these sites and is regarded as a significant bottleneck in achieving highly conformal dose distributions. Recent developments in radiation therapy have resulted in (i) motion-encompassing, (ii) respiratory gating, and (iii) tracking methods for adapting the radiation beam aperture to account for the respiration-induced target motion. The purpose of this review is to discuss the magnitude, impact, and management of respiration-induced tumor motion.

Investigating the Electronic Portal Imaging Device for Small Radiation Field Measurements.

PURPOSE: With the advent of state-of-the-art treatment technologies, the use of small fields has increased, and dosimetry in small fields is highly challenging. In this study, the potential use of Varian electronic portal imaging device (EPID) for small field measurements was explored for 6 and 15 MV photon beams. MATERIALS AND METHODS: The output factors and profiles were measured for a range of jaw-collimated square field sizes starting from 0.8 cm × 0.8 cm to 10 cm × 10 cm using EPID. For evaluation purpose, reference data were acquired using Exradin A16 microionization chamber (0.007 cc) for output factors and stereotactic field diode for profile measurements in a radiation field analyzer. RESULTS: The output factors of EPID were in agreement with the reference data for field sizes down to 2 cm × 2 cm and for 2 cm × 2 cm; the difference in output factors was +2.06% for 6 MV and +1.56% for 15 MV. For the lowest field size studied (0.8 cm × 0.8 cm), the differences were maximum; +16% for 6 MV and +23% for 15 MV photon beam. EPID profiles of both energies were closely matching with reference profiles for field sizes down to 2 cm × 2 cm; however, penumbra and measured field size of EPID profiles were slightly lower compared to its counterpart. CONCLUSIONS: EPID is a viable option for profile and output factor measurements for field sizes down to 2 cm × 2 cm in the absence of appropriate small field dosimeters.

Value of Minimum Apparent Diffusion Coefficient on Magnetic Resonance Imaging as a Biomarker for Predicting Progression of Disease Following Surgery and Radiotherapy in Glial Tumors from a Tertiary Care Center in Northern India.

PURPOSE: Studies have shown that cellularity of glial tumors are inversely correlated to minimum apparent diffusion coefficient (ADC) values derived on diffusion-weighted imaging (DWI). The purpose of this prospective exploratory study was to evaluate whether temporal change in "minimum ADC" values during follow-up predict progressive disease in glial tumors post radiotherapy and surgery. MATERIALS AND METHODS: Adult patients of glial tumors, subjected to surgery followed by Radiotherapy (RT), were included in the study. Serial conventional magnetic resonance imaging with DWI at the following time points - presurgery, pre-RT, post-RT imaging at 3, 7, and 15 months were done. For "minimum ADC" values, multiple regions of interest (ROI) were identified on ADC maps derived from DWI. A mean of 5 minimum ADC values was chosen as "minimum ADC" value. The correlation was drawn between histology and minimum ADC values and time trends were studied. RESULTS: Fourteen patients were included in this study. Histologies were low-grade glioma (LGG) - 5, anaplastic oligodendroglioma (ODG) -5, and glioblastoma multiforme (GBM) - 4. Minimum ADC values were significantly higher in LGG and GBM than ODG. Presurgery, the values were 0.812, 0.633, and 0.787 × 10-3 mm2/s for LGG, ODG, and GBM, respectively. DWI done at the time of RT planning showed values of 0.786, 0.636, 0.869 × 10-3 mm2/s, respectively. During follow-up, the increasing trend of minimum ADC was observed in LGG (P = 0.02). All these patients were clinically and radiologically stable. Anaplastic ODGs, however, showed an initial increase followed by the fall of minimum ADC in all the 5 cases (P = 0.00). Four of the five cases developed progressive disease subsequently. In all the 4 GBM cases, a consistent fall of minimum ADC values was observed (P = 0.00), and they all progressed in spite of RT. CONCLUSIONS: The DWI-derived minimum ADC values are an important yet simple quantitative tool to assess the treatment response and disease progression before they are evident on conventional imaging during the follow-up of glial tumors.

Estimation of the effects of normal tissue sparing using equivalent uniform dose-based optimization.

In this study, we intend to estimate the effects of normal tissue sparing between intensity modulated radiotherapy (IMRT) treatment plans generated with and without a dose volume (DV)-based physical cost function using equivalent uniform dose (EUD). Twenty prostate cancer patients were retrospectively selected for this study. For each patient, two IMRT plans were generated (i) EUD-based optimization with a DV-based physical cost function to control inhomogeneity (EUDWith DV) and (ii) EUD-based optimization without a DV-based physical cost function to allow inhomogeneity (EUDWithout DV). The generated plans were prescribed a dose of 72 Gy in 36 fractions to planning target volume (PTV). Mean dose, D30%, and D5% were evaluated for all organ at risk (OAR). Normal tissue complication probability was also calculated for all OARs using BioSuite software. The average volume of PTV for all patients was 103.02 ± 27 cm(3). The PTV mean dose for EUDWith DV plans was 73.67 ± 1.7 Gy, whereas for EUDWithout DV plans was 80.42 ± 2.7 Gy. It was found that PTV volume receiving dose more than 115% of prescription dose was negligible in EUDWith DV plans, whereas it was 28% in EUDWithout DV plans. In almost all dosimetric parameters evaluated, dose to OARs in EUDWith DV plans was higher than in EUDWithout DV plans. Allowing inhomogeneous dose (EUDWithout DV) inside the target would achieve better normal tissue sparing compared to homogenous dose distribution (EUDWith DV). Hence, this inhomogeneous dose could be intentionally dumped on the high-risk volume to achieve high local control. Therefore, it was concluded that EUD optimized plans offer added advantage of less OAR dose as well as selectively boosting dose to gross tumor volume.

Determination of optimal number of beams in direct machine parameter optimization-based intensity modulated radiotherapy for head and neck cases.

This paper aims to introduce an algorithm called "sensitivity-based beam number selection (SBBNS)" for fully automated and case-specific determination of an optimal number of equispaced beams in intensity-modulated radiotherapy (IMRT). We tested the algorithm in five head and neck cases of varying complexity. We used direct machine parameter optimization method coupled with Auto Plan feature available in Pinnacle TPS (Version 9.10.0) for optimization. The Pearson correlation test shows a correlation of 0.88 between predicted and actual optimal number of beams, which indicates that SBBNS method is capable of predicting optimal number of beams for head and neck cases with reasonable accuracy. The major advantage of the algorithm is that it intrinsically takes into account various case- and machine-specific factors for the determination of optimal number. The study demonstrates that the algorithm can be effectively applied to IMRT scenarios to determine case specific and optimal number of beams for head and neck cases.

Evaluating the four-dimensional cone beam computed tomography with varying gantry rotation speed.

OBJECTIVE: The purpose of this work was to evaluate the four-dimensional cone beam CT (4DCBCT) imaging with different gantry rotation speed. METHODS: All the 4DCBCT image acquisitions were carried out in Elekta XVI Symmetry™ system (Elekta AB, Stockholm, Sweden). A dynamic thorax phantom with tumour mimicking inserts of diameter 1, 2 and 3 cm was programmed to simulate the respiratory motion (4 s) of the target. 4DCBCT images were acquired with different gantry rotation speeds (36°, 50°, 75°, 100°, 150° and 200° min(-1)). Owing to the technical limitation of 4DCBCT system, average cone beam CT (CBCT) images derived from the 10 phases of 4DCBCT were used for the internal target volume (ITV) contouring. ITVs obtained from average CBCT were compared with the four-dimensional CT (4DCT). In addition, the image quality of 4DCBCT was also evaluated for various gantry rotation speeds using Catphan(®) 600 (The Phantom Laboratory Inc., Salem, NY). RESULTS: Compared to 4DCT, the average CBCT underestimated the ITV. The ITV deviation increased with increasing gantry speed (-10.8% vs -17.8% for 36° and 200° min(-1) in 3-cm target) and decreasing target size (-17.8% vs -26.8% for target diameter 3 and 1 cm in 200° min(-1)). Similarly, the image quality indicators such as spatial resolution, contrast-to-noise ratio and uniformity also degraded with increasing gantry rotation speed. CONCLUSION: The impact of gantry rotation speed has to be considered when using 4DCBCT for ITV definition. The phantom study demonstrated that 4DCBCT with slow gantry rotation showed better image quality and less ITV deviation. ADVANCES IN KNOWLEDGE: Usually, the gantry rotation period of Elekta 4DCBCT system is kept constant at 4 min (50° min(-1)) for acquisition, and any attempt of decreasing/increasing the acquisition duration requires careful investigation. In this study, the 4DCBCT images with different gantry rotation speed were evaluated.

Evaluating the image quality of cone beam CT acquired during rotational delivery.

OBJECTIVE: The aim of this work was to evaluate the quality of kilovoltage (kV) cone beam CT (CBCT) images acquired during arc delivery. METHODS: Arc plans were delivered on a Catphan(®) 600 phantom (The Phantom Laboratory Inc., Salem, NY), and kV CBCT images were acquired during the treatment. The megavoltage (MV) scatter effect on kV CBCT image quality was evaluated using parameters such as Hounsfield unit (HU) accuracy, spatial resolution, contrast-to-noise ratio (CNR) and spatial non-uniformity (SNU). These CBCT images were compared with reference scans acquired with the same acquisition parameters without MV "beam on". This evaluation was carried out for different photon beams (6 and 15 MV), arc types (half vs full arc), static field sizes (10 × 10 and 25 × 25 cm(2)) and source-to-imager distances (SID) (150 and 170 cm). RESULTS AND CONCLUSION: HU accuracy, CNR and SNU were considerably affected by MV scatter, and this effect was increased with increasing field size and decreasing photon energy, whereas the spatial resolution was almost unchanged. The MV scatter effect was observed to be more for full-rotation arc delivery than for half-arc delivery. In addition, increasing the SID resulted in decreased MV scatter effect and improved the image quality. ADVANCES IN KNOWLEDGE: Nowadays, volumetric modulated arc therapy (VMAT) is increasingly used in clinics, and this arc therapy enables us to acquire CBCT imaging simultaneously. But, the main issue of concurrent imaging is the "MV scatter" effect on CBCT imaging. This study aims to experimentally quantify the effect of MV scatter on CBCT image quality.

Performance evaluation of respiratory motion-synchronized dynamic IMRT delivery.

The purpose of this study was to evaluate the capabilities of DMLC to deliver the respiratory motion-synchronized dynamic IMRT (MS-IMRT) treatments under various dose rates. In order to create MS-IMRT plans, the DMLC leaf motions in dynamic IMRT plans of eight lung patients were synchronized with the respiratory motion of breathing period 4 sec and amplitude 2 cm (peak to peak) using an in-house developed leaf position modification program. The MS-IMRT plans were generated for the dose rates of 100 MU/min, 400 MU/min, and 600 MU/min. All the MS-IMRT plans were delivered in a medical linear accelerator, and the fluences were measured using a 2D ion chamber array, placed over a moving platform. The accuracy of MS-IMRT deliveries was evaluated with respect to static deliveries (no compensation for target motion) using gamma test. In addition, the fluences of gated delivery of 30% duty cycle and non- MS-IMRT deliveries were also measured and compared with static deliveries. The MS-IMRT was better in terms of dosimetric accuracy, compared to gated and non-MS-IMRT deliveries. The dosimetric accuracy was observed to be significantly better for 100 MU/min MS-IMRT. However, the use of high-dose rate in a MS-IMRT delivery introduced dose-rate modulation/beam hold-offs that affected the synchronization between the DMLC leaf motion and target motion. This resulted in more dose deviations in MS-IMRT deliveries at the dose rate of 600 MU/min.

Investigating the effect of dose rate and maximum allowable MLC leaf velocity in dynamic IMRT.

The purpose of this study is to analyze the effect of various dose rates (DR) and maximum allowable MLC leaf velocities (MLV) in dynamic Intensity Modulated Radiotherapy (IMRT) planning and delivery of head and neck patients. Five head and neck patients were retrospectively included in this study. The initial dynamic IMRT 'reference plans' were created for all these patients, using a DR of 400 MU/min and MLV of 2.5 cm/s. Additional plans were generated by varying the DR and MLV values. The DR value was varied from 100 to 600 MU/min, in increments of 100 MU/min, for a MLV of 2.5 cm/s. Also the MLV was varied from 0.5 to 3 cm/s, in increments of 0.5 cm, for a DR of 400 MU/min. In order to maintain the prescribed dose to the PTV, the DR was allowed to vary ('beam hold or DR modulation' during delivery) when the MLV was changed and the MLV was allowed to vary when the DR was changed. The mean doses to the PTV as well as parotids, maximum dose of spinal cord and total MU were recorded for analysis. The effect of DR and MLV on treatment delivery was analyzed using the portal dosimetry for all the above plans. The predicted portal dose fluences of the TPS were compared with the measured EPID fluences using gamma evaluation criteria of 2% dose difference and 2 mm distance to agreement. A small proportional increase in OAR doses with DR was observed. Increases to MLV value resulted in decreases of the OAR doses and this effect was considerable for values below 1.5 cm/s. DR and MLV both resulted in no appreciable dose variation to the target. The total MU to deliver the plan increases with increasing DR and decreasing MLV. When comparing portal images derived from the treatment plans with portal images obtained by delivering the treatments, it was observed that the treatments was most reliably delivered when the DRs were set to lower values and when the MLVs were set to higher values.

Medulloblastomas: clinical profile, treatment techniques and outcome - an institutional experience.

The present series reports an audit on the patterns of presentation, radiation treatment techniques, failure pattern and outcome in the 36 patients treated at a single institution. Patients were accrued between October 1991 and September 1999. They underwent total or subtotal resection along with craniospinal irradiation. The dose to the cranium ranged from 30 to 43Gy (median- 36Gy), to the spine from 20 - 36Gy (median- 36Gy) and the posterior fossa boost, which was delivered in 32 cases, ranged from 14 to 24Gy (median -18Gy). Simulator film evaluation was carried out at the time of analysis based on the French Medulloblastoma Group guidelines, which revealed a significant under-dosage in the region of posterior fossa and cribriform plate in 27% and 19% respectively. Adjuvant chemotherapy was administered in 7 patients. Salvage treatment in the form of chemotherapy (5 cases) and re-irradiation (2 cases) were attempted but were ineffective. The overall survival (OS) and progression free survival (PFS) rates were 54% and 40% respectively, with the median being 75 and 29 months respectively. Amongst all the prognostic factors considered, on univariate analysis, duration of symptoms was significant for PFS with a trend towards significance for OS, while extent of debulking had a trend towards significance for PFS. No factor emerged significant on multivariate analysis.