Initial Intensity-modulated Radiotherapy Research Articles

Simulation and pre-planning omitted radiotherapy (SPORT): a feasibility study for prostate cancer

This study explored the feasibility of on-couch intensity modulated radiotherapy (IMRT) planning for prostate cancer (PCa) on a cone-beam CT (CBCT)-based online adaptive RT platform without an individualized pre-treatment plan and contours. Ten patients with PCa previously treated with image-guided IMRT (60 Gy/20 fractions) were selected. In contrast to the routine online adaptive RT workflow, a novel approach was employed in which the same preplan that was optimized on one reference patient was adapted to generate individual on-couch/initial plans for the other nine test patients using Ethos emulator. Simulation CTs of the test patients were used as simulated online CBCT (sCBCT) for emulation. Quality assessments were conducted on synthetic CTs (sCT). Dosimetric comparisons were performed between on-couch plans, on-couch plans recomputed on the sCBCT and individually optimized plans for test patients. The median value of mean absolute difference between sCT and sCBCT was 74.7 HU (range 69.5–91.5 HU). The average CTV/PTV coverage by prescription dose was 100.0%/94.7%, and normal tissue constraints were met for the nine test patients in on-couch plans on sCT. Recalculating on-couch plans on the sCBCT showed about 0.7% reduction of PTV coverage and a 0.6% increasing of hotspot, and the dose difference of the OARs was negligible (<0.5 Gy). Hence, initial IMRT plans for new patients can be generated by adapting a reference patient’s preplan with online contours, which had similar qualities to the conventional approach of individually optimized plan on the simulation CT. Further study is needed to identify selection criteria for patient anatomy most amenable to this workflow.

Normal tissue complication probability model of temporal lobe injury following re-irradiation of IMRT for local recurrent nasopharyngeal carcinoma.

We tried to establish the normal tissue complication probability (NTCP) model of temporal lobe injury of recurrent nasopharyngeal carcinoma (NPC) patients after two courses of intensity modulated radiotherapy (IMRT) to provide more reliable dose-volume data reference to set the temporal lobe tolerance dose for recurrent NPC patients in the future. Recurrent NPC patients were randomly divided into training data set and validation data set in a ratio of 2:1, All the temporal lobes (TLs) were re-contoured as R/L structures and named separately in the MIM system. The dose distribution of the initial IMRT plan was deformed into the second course planning CT via MIM software to get the deformed dose. Equivalent dose of TLs in 2Gy fractions was calculated via linear quadratic model, using an α/β=3 for temporal lobes. NTCP model that correlated the irradiated volume of the temporal lobe and? the clinical variables were evaluated in a multivariate prediction model using AUC analysis. From Jan. 2010 to Dec. 2020, 78 patients were enrolled into our study. Among which 26 (33.3%) developed TLI. The most important factors affecting TLI was the sum-dose d1.5cc of TL, while the possible clinical factors did not reach statistically significant differences in multivariate analysis. According to NTCP model, the TD5 and TD50 EQD2 dose of sum-dose d1.5cc were 65.26Gy (46.72-80.69Gy) and 125.25Gy (89.51-152.18Gy), respectively. For the accumulated EQD2 dose, the area under ROC shadow was 0.8702 (0.7577-0.9828) in model validation, p<0.001. In this study, a NTCP model of temporal lobe injury after a second course of IMRT for recurrent nasopharyngeal carcinoma was established. TD5 and TD50 doses of temporal lobe injury after re-RT were obtained according to the model, and the model was verified by validation set data.

Patterns and prognosis of regional recurrence in nasopharyngeal carcinoma after intensity-modulated radiotherapy.

We analyzed the patterns of lymph node (LN) failure and prognosis in patients with regional recurrent nasopharyngeal carcinoma (rNPC) alone after primary intensity-modulated radiotherapy (IMRT). A total of 175 patients who were treated with IMRT between 2010 and 2015 and who experienced regional recurrence alone were included. Recurrent LNs were re-located in the initial pretreatment imaging and IMRT plan and failures were classified as in-field or out-field based on target volume delineation. All patients underwent curative salvage treatment. Independent prognostic factors for overall survival (OS) were selected by multivariate Cox analysis. Level IIb (49.1%, 86/175) was the most frequent recurrence site, followed by level IIa (36%), level III (18.9%), level IVa (12%), the retropharyngeal region (8%), level Va (6.9%), and the parotid region (6.9%). A total of 264 recurrent LNs were recorded: 149 (56.4%) were classified as in-field failure with a prescribed dose ≥66 Gy, 60 (22.7%) with 60 to <66 Gy, 32 (12.1%) with 50 to <60 Gy, and 23 (8.7%) as an out-field failure, which mainly occurred in the parotid region and level Ib. After a median follow-up of 52.8months, the estimated 5-year OS rate was 66.9%. Multivariate analysis showed that age, plasma Epstein-Barr virus DNA level, extranodal extension, lower neck involvement, and parotid LN recurrence were independent prognostic factors of OS. In-field failure represented the main pattern of regional recurrence and out-field failure mainly occurred in the parotid gland and level Ib. Patients with regional rNPC alone had a good prognosis after salvage treatment.

Long-term Patterns of Failure and the Value of Blood Prognostic Markers in Anal Cancers Treated With Intensity-Modulated Radiation Therapy

BackgroundTo analyze the long-term outcomes and prognostic value of hematological parameters in anal cancer patients receiving intensity-modulated radiation therapy (IMRT). MaterialsHospital records of consecutive patients with anal squamous cell carcinoma who received curative-intent IMRT according to a standardized contouring protocol between 2010 and 2020 were reviewed. Locoregional failure-free survival (LRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) were estimated using the Kaplan-Meier method. Coverage of locoregional recurrences by the initial IMRT volumes were assessed. The prognostic value of pretreatment blood counts for PFS and OS were determined using Cox regression analysis. ResultsA total of 166 patients were analyzed with a median follow-up of 3.3 years. Forty-six percent and 54% of patients had Stage I-II and IIIA-B cancers, respectively. The 5-year LRFS, DMFS, PFS and OS were 81%, 89%, 65% and 76% respectively. Grade ≥ 3 toxicity occurred in 5% of patients. Of all patients who relapsed, 70% had only locoregional recurrence as first site of failure. Ninety percent of locoregional recurrences were in-field. Hemoglobin, neutrophil and platelet counts were associated with PFS on univariable analysis, but only cancer stage and p16 status remained prognostic on multivariable analysis. Patients with more advanced cancer stages also had higher baseline neutrophil counts. Performance status and neutrophil counts were prognostic for OS on multivariable analysis. ConclusionThis study affirms the long-term efficacy and safety of IMRT. Treatment resistance, rather than radiation geographic miss, is a major issue underpinning locoregional recurrences. Pretreatment blood counts were not validated to be independently prognostic for disease recurrence.

Appropriate reduction of the fragmentation level of subfield sequences to improve the accuracy of field delivery in IMRT for nasopharyngeal carcinoma.

Objective:Due to the influence of gravity, inertia and friction, there will be deviation between the position of multileaf collimator (MLC) in the delivered field and the initial intensity modulated radiotherapy (IMRT) plan. This study explores the effects of the fragmentation level of subfield sequences on this deviation and seeks ways to improve the accuracy of field delivery in IMRT for nasopharyngeal carcinoma (NPC).Methods:30 patients with NPC were selected, and two groups (groups A and B) of IMRT plans were made in Pinnacle planning system. Different planning parameters were used for optimization so that the subfield sequence fragmentation level of Group B was significantly lower than that of Group A. With the MapCheck2, verification plan was implemented in two ways: 0o gantry angle and the actual treatment angle, then the differences between the two verification results of each group plan were analyzed.Results:The γ-passing rate verified at the actual treatment angle was lower than that of 0o gantry angle for each group plan, whereas the Group B plan shows small reduction. Mean change value (Δ) was decreased from 1.01% (Group A) to 0.40% (Group B) with 3%/3 mm criteria and 2.88% (Group A) to 1.52% (Group B) with 2%/2 mm criteria, respectively. The smaller the difference (Δ), the actual output dose of the field is more consistent with the original plan. There was no significant correlation between this change and the angle of the field.Conclusion:Appropriately reducing the fragmentation level of subfield sequence can reduce the effect of field angle on MLC position and improve the delivery accuracy of IMRT plan.Advances in knowledge:The fragmentation level of the subfield sequence may have an impact on the accuracy of the delivery of the plan. This study demonstrates this assumption by comparing the differences between 0° and actual angle verification. Mean change value (Δ) was decreased from Group A to Group B. The smaller the difference (Δ), the actual output dose of the field is more consistent with the original plan. The result of this study may help us to understand that appropriately increasing the subfield area and reducing the fragmentation level of the subfield sequence can reduce the difference between the two verification results, which can further improve the accuracy of the plan delivery in IMRT and tumor treatment.

Retrospective study comparing MR-guided radiation therapy (MRgRT) setup strategies for prostate treatment: repositioning vs. replanning

BackgroundThis study compared adaptive replanning and repositioning corrections based on soft-tissue matching for prostate cancer by using the magnetic resonance-guided radiation therapy (MRgRT) system.MethodsA total of 19 patients with prostate cancer were selected retrospectively. Weekly magnetic resonance image (MRI) scans were acquired for 5 weeks for each patient to observe the anatomic changes during the treatment course. Initial intensity-modulated radiation therapy (IMRT) plans (iIMRT) were generated for each patient with 13 coplanar 60Co beams on a ViewRay™ system. Two techniques were applied: patient repositioning and replanning. For patient repositioning, one plan was created: soft-tissue (prostate) matching (Soft). The dose distribution was calculated for each MRI with the beam delivery parameters from the initial IMRT plan. The replanning technique was used to generate the Adaptive plan, which was the reoptimized plan for the weekly MRI. The dose-volumetric parameters of the planning target volume (PTV), bladder, and rectum were calculated for all plans. During the treatment course, the PTV, bladder, and rectum were evaluated for changes in volume and the effect on dosimetric parameters. The differences between the dose-volumetric parameters of the plans were examined through the Wilcoxon test. The initial plan was used as a baseline to compare the differences.ResultsThe Adaptive plan showed better target coverage during the treatment period, but the change was not significant in the Soft plan. There were significant differences in D98%, D95%, and D2% in PTV between the Soft and Adaptive plans (p < 0.05) except for Dmean. There was no significant change in Dmax and Dmean as the treatment progressed with all plans. All indices for the Adaptive plan stayed the same compared to those of iIMRT during the treatment course. There were significant differences in D15%, D25%, D35%, and D50% in the bladder between the Soft and Adaptive plans. The Adaptive plan showed the worse dose sparing than the Soft plan for the bladder according to each dosimetric index. In contrast to the bladder, the Adaptive plan achieved better sparing than the Soft plan during the treatment course. The significant differences were only observed in D15% and D35% between the Soft and Adaptive plans (p < 0.05).ConclusionsPatient repositioning based on the target volume (Soft plan) can relatively retain the target coverage for patients and the OARs remain at a clinically tolerance level during the treatment course. The Adaptive plan did not clinically improve for the dose delivered to OARs, it kept the dose delivered to the target volume constant. However, the Adaptive plan is beneficial when the organ positions and volumes change considerable during treatment.

PTV margin analysis for prostate patients treated with initial pelvic nodal IMRT and prostate proton boost

To evaluate the planning target volume (PTV) margins for prostate cancer patients treated with initial intensity-modulated radiation therapy (IMRT) to pelvic lymph nodes and a proton boost to the prostate using cone-beam computed tomography (CBCT) and radiographs as image guidance. We analyzed data from prostate patients (n = 15) treated with initial pelvic IMRT and a proton boost to the prostate. CBCT and 2-dimensional (2D) radiographs were used for IMRT and proton pre-treatment alignments, respectively. Translations from bony-matching, implanted marker seed matching, and seed-bony differences were obtained from CBCTs. Pretreatment and post-treatment 2D radiographs were analyzed for residual setup errors and intrafractional organ motion. PTV margins of prostate and pelvic lymph nodes for seed-matching, bony-matching and the skin mark-matching approach were obtained using 2.5 * Σ + 0.7 * σ formula, where Σ is the systematic error and σ is the random error summed in quadrature of various error components. For the seed-matching approach, the prostate margins were 1.5 mm, 3.5 mm, and 2.7 mm for the left-right (LR), superior-inferior (SI), and anterior-posterior (AP) directions, respectively; pelvic lymph node margins were 2.3 mm, 7.1 mm, and 7.0 mm. For the bony-matching approach, the prostate margins were 2.7 mm, 7.8 mm, and 7.5 mm for the LR, SI, and AP directions, respectively; pelvic lymph node margins were 0.7 mm, 1.5 mm, and 1.4 mm. For the skin mark-matching approach, the prostate margins were 7.6 mm, 13.4 mm, and 11.4 mm for the LR, SI, and AP directions, respectively; pelvic lymph node margins were 8.2 mm, 12.6 mm, and 12.3 mm. The seed-matching approach, as compared to the bony-matching approach, reduced prostate margins, which may in turn reduce dose to the bladder and rectum at the expense of increased but acceptable margins for the pelvic lymph nodes.

Analysis of rare periparotid recurrence after parotid gland-sparing intensity-modulated radiotherapy for nasopharyngeal carcinoma

PurposePeriparotid recurrence is an uncommon phenomenon after intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma. This study aimed to discuss the clinical characteristics, reasonable causes and feasible therapeutic modalities of patients with nasopharyngeal carcinoma and periparotid recurrence. Patients and methodsThe medical records of 1852 patients with non-metastatic nasopharyngeal carcinoma treated with initial IMRT between January 2008 and December 2012 were retrospectively reviewed, and nine patients were finally found to have developed periparotid recurrence after IMRT. After periparotid failure, four received radiotherapy and chemotherapy, two had surgery, two had surgery and adjuvant radiotherapy or chemotherapy, and one received radiotherapy alone. ResultThe incidence rate of periparotid recurrence was 4.9‰. According to pretreatment magnetic resonance imaging (MRI) scans, all patients had both ipsilateral retropharyngeal lymph nodes metastasis with 66.7% of extracapsular spread and level II lymphadenopathy with all extracapsular spread. The median time interval to periparotid failure was 14.8 months, and six patients were found to have a relapse in the primary sites of unsuspicious parotid nodules. After a median follow-up of 46.4 months, five patients developed distant metastasis, three of them developed local failure. In addition, one developed regional failure, one developed locoregional recurrence, and only one was alive without evidence of disease at the last follow-up. ConclusionPeriparotid recurrences are rare after definitive IMRT for nasopharyngeal carcinoma. However, patients with ipsilateral retropharyngeal lymph nodes or level II nodal extracapsular spread on pretreatment MRI could be suspicious of metastatic periparotid nodules. Distant metastases were the main treatment failure despite a combination of several salvage treatment of periparotid recurrence. More effective chemotherapy should be explored.

Intensity-modulated radiotherapy for gliomas:dosimetric effects of changes in gross tumor volume on organs at risk and healthy brain tissue.

AimThe aim of this study was to explore the effects of changes in the gross tumor volume (GTV) on dose distribution in organs at risk (OARs) and healthy brain tissue in patients with gliomas.MethodsEleven patients suffering from gliomas with intensity-modulated radiotherapy (IMRT) plans treated with a simultaneous integrated boost technique planned before therapy (initial plans) were prospectively enrolled. At the end of radiotherapy, patients underwent repeat computed tomography and magnetic resonance imaging, and IMRT was replanned. The GTV and dosimetric parameters between the initial and replanned IMRT were compared using the Wilcoxon two-related-sample test, and correlations between the initial GTV and the replanned target volumes were assessed using the bivariate correlation test.ResultsThe volume of the residual tumor did not change significantly (P>0.05), the volume of the surgical cavity decreased significantly (P<0.05), and the GTV and target volumes decreased significantly at the end of IMRT (all P<0.05). The near-maximum dose to OARs and volumes of healthy brain tissue receiving total doses of 10–50 Gy were lower in the replanned IMRT than in the initial IMRT (all P<0.05). The GTV in the initial plan was significantly positively correlated with the changes in the GTV and planning target volume 1 that occurred during IMRT (all P<0.05).ConclusionThe reduction in the GTV in patients with gliomas resulted from shrinkage of the surgical cavity during IMRT, leading to decreased doses to the OARs and healthy brain tissue. Such changes appeared to be most meaningful in patients with large initial GTV values.

An analysis of clinical and dosimetric factors for postradiation nasopharyngeal necrosis in intensity-modulated radiotherapy for nasopharyngeal carcinoma

Objective To investigate the influencing factors for postradiation nasopharyngeal necrosis (PRNN) by analyzing clinical characteristics, prognosis, and dosimetry of PRNN after initial intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). Methods A retrospective analysis was performed among 1217 patients with NPC who received initial IMRT from 2001 to 2013. Twenty-one patients were diagnosed with PRNN by clinical symptoms, endoscopy, magnetic resonance imaging, and pathological evidence (not including local recurrence). The clinical characteristics and prognosis were summarized and the radiotherapy plans were reassessed for dosimetric evaluation. Results In the 21 patients with PRNN, 17 were male and 4 female; one patient was in stage T2, 3 in stage T3, and 17 in stage T4. The median volume of gross tumor was 83 cm3. All patients received radiotherapy with a prescribed dose of 73.92 Gy except one patient with stage T2 disease who received a prescribed dose of 69.96 Gy. The time to PRNN after radiotherapy ranged between 1.8 and 21.9 months (median time=6.2 months). The incidence of massive nasopharyngeal bleeding was 48%(10/21). In the 21 patients, 6 recovered form PRNN, 15 remained ill, and 8 patients died, consisting of 4 who died of massive nasopharyngeal bleeding, 3 of cachexia with multiple organ failure, and 1 of multiple bone metastases. Conclusions PRNN is one of the severe adverse reactions after IMRT for NPC. The development of PRNN is related to advanced T stage, large tumor volume, poor nutritional status, infection, radiotherapy dose, and intense treatment. Massive nasopharyngeal bleeding and cachexia are the primary causes of death in patients with PRNN. Key words: Nasopharyngeal neoplasms/three-dimensional radiotherapy; Radiation nasopharyngeal necrosis; Factor analysis

Benefits of adaptive radiation therapy in lung cancer as a function of replanning frequency.

To quantify the potential benefit associated with daily replanning in lung cancer in terms of normal tissue dose sparing and to characterize the tradeoff between adaptive benefit and replanning frequency. A set of synthetic images and contours, derived from weekly active breathing control images of 12 patients who underwent radiation therapy treatment for nonsmall cell lung cancer, is generated for each fraction of treatment using principal component analysis in a way that preserves temporal anatomical trends (e.g., tumor regression). Daily synthetic images and contours are used to simulate four different treatment scenarios: (1) a "no-adapt" scenario that simulates delivery of an initial plan throughout treatment, (2) a "midadapt" scenario that implements a single replan for fraction 18, (3) a "weekly adapt" scenario that simulates weekly adaptations, and (4) a "full-adapt" scenario that simulates daily replanning. An initial intensity modulated radiation therapy plan is created for each patient and replanning is carried out in an automated fashion by reoptimizing beam apertures and weights. Dose is calculated on each image and accumulated to the first in the series using deformable mappings utilized in synthetic image creation for comparison between simulated treatments. Target coverage was maintained and cord tolerance was not exceeded for any of the adaptive simulations. Average reductions in mean lung dose (MLD) and volume of lung receiving 20 Gy or more (V20lung) were 65 ± 49 cGy (p = 0.000 01) and 1.1% ± 1.2% (p = 0.0006), respectively, for all patients. The largest reduction in MLD for a single patient was 162 cGy, which allowed an isotoxic escalation of the target dose of 1668 cGy. Average reductions in cord max dose, mean esophageal dose (MED), dose received by 66% of the heart (D66heart), and dose received by 33% of the heart (D33heart), were 158 ± 280, 117 ± 121, 37 ± 77, and 99 ± 120 cGy, respectively. Average incremental reductions in MLD for the midadapt, weekly adapt, and full-adapt treatments were 38, 18, and 8 cGy, respectively. Incremental reductions in MED for the same treatments were 57, 37, and 23 cGy. Reductions in MLD and MED for the full-adapt treatment were correlated with the absolute decrease in the planning target volume (r = 0.34 and r = 0.26). Adaptive radiation therapy for lung cancer yields clinically relevant reductions in normal tissue doses for frequencies of adaptation ranging from a single replan up to daily replanning. Increased frequencies of adaptation result in additional benefit while magnitude of benefit decreases.

A simple optimization approach for improving target dose homogeneity in intensity-modulated radiotherapy for sinonasal cancer.

Homogeneous target dose distribution in intensity-modulated radiotherapy (IMRT) for sinonasal cancer (SNC) is challenging to achieve. To solve this problem, we established and evaluated a basal-dose-compensation (BDC) optimization approach, in which the treatment plan is further optimized based on the initial plans. Generally acceptable initial IMRT plans for thirteen patients were created and further optimized individually by (1) the BDC approach and (2) a local-dose-control (LDC) approach, in which the initial plan is further optimized by addressing hot and cold spots. We compared the plan qualities, total planning time and monitor units (MUs) among the initial, BDC, LDC IMRT plans and volumetric modulated arc therapy (VMAT) plans. The BDC approach provided significantly superior dose homogeneity/conformity by 23%–48%/6%–9% compared with both the initial and LDC IMRT plans, as well as reduced doses to the organs at risk (OARs) by up to 18%, with acceptable MU numbers. Compared with VMAT, BDC IMRT yielded superior homogeneity, inferior conformity and comparable overall OAR sparing. The planning of BDC, LDC IMRT and VMAT required 30, 59 and 58 minutes on average, respectively. Our results indicated that the BDC optimization approach can achieve significantly better dose distributions with shorter planning time in the IMRT for SNC.

Determination of optimal planning target volume margins in patients with gynecological cancer

PurposeTo define optimal planning target volume (PTV) margins for intensity modulated radiotherapy (IMRT) ± knee-heel support (KHS) in patients treated with adjuvant radiotherapy. MethodsComputed tomography (CT) scans ± KHS of 10 patients were taken before and at 3rd and 5th week of treatment, fused and compared with initial IMRT plans. ResultsA PTV margin of 15 mm in anteroposterior (AP) and superoinferior (SI) directions and 5 mm in lateral directions were found to be adequate without any difference between ± KHS except for the SI shifts in CTV-primary at the 3rd week. Five mm margin for iliac CTV was found to be inadequate in 10–20% of patients in SI directions however when 7 mm margin was given for iliac PTV, it was found to be adequate. For presacral CTV, it was found that the most striking shift of the target volume was in the direction of AP. KHS caused significantly less volume of rectum and bladder in the treated volume. ConclusionsPTV margin of 15 mm in SI and AP, and 5 mm in lateral directions for CTV-primary were found to be adequate. A minimum of 7 mm PTV margin should be given to iliac CTV. The remarkable shifting in presacral CTV was believed to be due to the unforeseen hip malposition of obese patients. The KHS seems not to provide additional beneficial effect in decreasing the shifts both in CTV-primary and lymphatic, however it may have a beneficial effect of decreasing the OAR volume in PTV margins.

Dose Escalation for Locally Advanced Lung Cancer Using Adaptive Radiation Therapy With Simultaneous Integrated Volume-Adapted Boost

To test the feasibility of a planned phase 1 study of image-guided adaptive radiation therapy in locally advanced lung cancer. Weekly 4-dimensional fan beam computed tomographs (4D FBCT) of 10 lung cancer patients undergoing concurrent chemoradiation therapy were used to simulate adaptive radiation therapy: After an initial intensity modulated radiation therapy plan (0-30 Gy/2 Gy), adaptive replanning was performed on week 2 (30-50 Gy/2 Gy) and week 4 scans (50-66 Gy/2 Gy) to adjust for volume and shape changes of primary tumors and lymph nodes. Week 2 and 4 clinical target volumes (CTV) were deformably warped from the initial planning scan to adjust for anatomical changes. On the week 4 scan, a simultaneous integrated volume-adapted boost was created to the shrunken primary tumor with dose increases in 5 0.4-Gy steps from 66 Gy to 82 Gy in 2 scenarios: plan A, lung isotoxicity; plan B, normal tissue tolerance. Cumulative dose was assessed by deformably mapping and accumulating biologically equivalent dose normalized to 2 Gy-fractions (EQD2). The 82-Gy level was achieved in 1 in 10 patients in scenario A, resulting in a 13.4-Gy EQD2 increase and a 22.1% increase in tumor control probability (TCP) compared to the 66-Gy plan. In scenario B, 2 patients reached the 82-Gy level with a 13.9 Gy EQD2 and 23.4% TCP increase. The tested image-guided adaptive radiation therapy strategy enabled relevant increases in EQD2 and TCP. Normal tissue was often dose limiting, indicating a need to modify the present study design before clinical implementation.

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.

Clinical Outcome Of Patients Treated With IMRT For Locally Advanced Anal Canal Cancer

To assess clinical outcome of patients treated by Intensity-Modulated Radiation Therapy (IMRT) for squamous cell carcinoma of the anal canal. Since August 2007, 71 patients with anal squamous cell carcinoma were treated with IMRT in our institution. Concurrent chemotherapy was added according to our guidelines for locally advanced tumors (> 40mm and/or positive node). Radiation course consisted in delivering an initial IMRT plan i.e. to the PTV1 defined as the primary tumor and the risk area including pelvic and inguinal nodes. Forty-five Gray in 1.8 Gy-daily fractions were delivered five days a week. A second IMRT plan of 14.4-20 Gy to the primary tumor (PTV2) was administered in 1.8-2 Gy-daily fractions, 5 days a week. Dosimetric results were evaluated by dose-volume histograms for PTV and organs at risk (OAR). We present the results of the first 39 patients treated from August 2007 to January 2011 with a median follow-up of 24 months. Acute and late toxicities were scored according to the Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE v3.0). Thirty-one women and eight men were included in the present analysis. Tumors were classified as stages I, II, III in 2, 7, 27, and 2 patients, respectively. Median age was 59 years (range 38-85). Three patients were HIV positive. Radiotherapy alone or combined with chemotherapy were delivered in 6 (15%) and 33 (85%) patients, respectively. The dose-volume histogram (DVH) of the PTV2 showed an adequate coverage in terms of D2% (104.4 ± 8%) and D98% (98.14 ± 1.66%). Median values of V40 (volume receiving more than 40 Gy) and V30 were 47 and 76% for bowel , 51 and 84% for bladder and 1.6 and 45% for genitalia/perineum. Medians of V10 and V20 IBM were 51 and 35%. Treatment was well tolerated. Six patients (15%) required a treatment break of a median duration of 8 days (range 3-14 days). Acute grade 3 gastrointestinal and genitourinary toxicities were seen in 10 and 5% of patients, respectively. Grade 4 toxicity was only hematologic and was seen in 12% patients receiving concurrent chemoradiotherapy. With a median follow-up of 24 months, no patient experienced a grade 4 late toxicity and only 3 patients experienced a grade 3, one had vaginal fibrosis, and two others reported GI toxicities. The 2-year overall survival rate was 89%, the 2-year local relapse free survival was 77%, and the 2-year colostomy free survival rate was 85%. IMRT is well tolerated in terms of acute and late toxicity, allowing a treatment without interruption and dose escalation which may have an impact on clinical outcome.

A Dosimetric Planning Study Comparing Intensity-modulated Radiotherapy with Four-field Conformal Pelvic Radiotherapy for the Definitive Treatment of Cervical Carcinoma

AimsTo compare the dose to organs at risk (OAR) between a conventional four-field whole pelvis radiotherapy (4F-WPRT) plan and an initial single intensity-modulated WPRT (IM-WPRT) plan for definitive treatment of cervical cancer. The magnitude of potential dose sparing of OAR is unknown when planning target volumes are defined to include potential organ motion and microscopic disease extent. Materials and MethodsPlanning computed tomography scans of 50 consecutive, previously treated patients were re-planned using 4F-WPRT and IM-WPRT. Margins compatible with the literature on organ motion were used to create the planning target volume. Dose–volume histograms for target and OAR were compared for each patient with paired t-tests and waterfall plots. ResultsThe mean target volume covered by 95% (V47.8) was 99.7% for 4F-WPRT and 98.8% for IM-WPRT (P>0.05, ns). Intensity-modulated radiotherapy (IMRT) was associated with a significant reduction in the dose to OAR at the V50, V45, V40 and V30 level. There was a >20% difference in V50 in most patients: 84% (bladder), 58% (small bowel), 54% (sigmoid) and 84% (rectum). ConclusionsA single, initial IMRT plan with appropriate margins encompassing initial gross and potential microscopic pelvic disease leads to a reduction in the dose to OAR without compromising target coverage. This offers a potential ‘class solution’ for definitive treatment of patients with cervical cancer. Clinical outcome data are still needed to verify this planning study.

Comparative Toxicity and Dosimetric Profile of Whole-Pelvis Versus Prostate Bed-Only Intensity-Modulated Radiation Therapy After Prostatectomy

To assess whether whole-pelvis (WP) intensity modulated radiation therapy (IMRT) for prostate cancer (PCa) after prostatectomy is associated with increased toxicity compared to prostate-bed only (PB) IMRT. All patients (n= 67) undergoing postprostatectomy IMRT to 70.2 Gy at our institution from January 2006 to January 2009 with minimum 12-month follow-up were divided into WP (n= 36) and PB (n= 31) comparison groups. WP patients received initial pelvic nodal IMRT to 45 Gy. Pretreatment demographics, bladder and rectal dose-volume histograms, and maximum genitourinary (GU) and gastrointestinal (GI) toxicities were compared. Logistic regression models evaluated uni- and multivariate associations between pretreatment demographics and toxicities. Pretreatment demographics including age and comorbidities were similar between groups. WP patients had higher Gleason scores, T stages, and preoperative prostate-specific antigen (PSA) levels, and more WP patients underwent androgen deprivation therapy (ADT). WP minimum (Dmin) and mean bladder doses, bladder volumes receiving more than 5 Gy (V5) and V20, rectal Dmin, and PB bladder and rectal V65 were significantly increased. Maximum acute GI toxicity was Grade 2 and was increased for WP (61%) vs. PB (29%) patients (p= 0.001); there was no significant difference in acute Grade ≥2 GU toxicity (22% WP vs. 10% PB; p= 0.193), late Grade ≥2 GI toxicity (3% WP vs. 0% PB; p= 0.678), or late Grade ≥2 GU toxicity (28% WP vs. 19% PB; p= 0.274) with 25-month median follow-up (range, 12-44 months). On multivariate analysis, long-term ADT use was associated with Grade ≥2 late GU toxicity (p= 0.02). Despite dosimetric differences in irradiated bowel, bladder, and rectum, WP IMRT resulted only in clinically significant increased acute GI toxicity in comparison to that with PB IMRT, with no differences in GU or late GI toxicity.

Clinical Toxicities and Dosimetric Parameters After Whole-Pelvis Versus Prostate-Only Intensity-Modulated Radiation Therapy for Prostate Cancer

To assess whether whole-pelvis (WP) intensity-modulated radiation therapy (IMRT) is associated with increased toxicity compared with prostate-only (PO) IMRT. We retrospectively analyzed all patients with prostate cancer undergoing definitive IMRT to 79.2 Gy with concurrent androgen deprivation at our institution from November 2005 to May 2007 with a minimum follow-up of 12 months. Thirty patients received initial WP IMRT to 45 Gy in 1.8-Gy fractions, and thirty patients received PO IMRT. Study patients underwent computed tomography simulation and treatment planning by use of predefined dose constraints. Bladder and rectal dose-volume histograms, maximum genitourinary (GU) and gastrointestinal (GI) Radiation Therapy Oncology Group toxicity grade, and late Grade 2 or greater toxicity-free survival curves were compared between the two groups by use of the Student t test, Fisher exact test, and Kaplan-Meier curve, respectively. Bladder minimum dose, mean dose, median dose, volume receiving 5 Gy, volume receiving 20 Gy, volume receiving 40 Gy, and volume receiving 45 Gy and rectal minimum dose, median dose, and volume receiving 20 Gy were significantly increased in the WP group (all p values < 0.01). Maximum acute GI toxicity was limited to Grade 2 and was significantly increased in the WP group at 50% vs. 13% the PO group (p = 0.006). With a median follow-up of 24 months (range, 12-35 months), there was no difference in late GI toxicity (p = 0.884) or in acute or late GU toxicity. Despite dosimetric differences in the volume of bowel, bladder, and rectum irradiated in the low-dose and median-dose regions, WP IMRT results only in a clinically significant increase in acute GI toxicity, in comparison to PO IMRT, with no difference in GU or late GI toxicity.

Adverse Events Associated With Concurrent Chemoradiation Therapy in Patients With Head and Neck Cancer

To assess toxicities, functional outcomes, and health-related quality of life associated with concurrent chemoradiation therapy (CRT) in patients with head and neck cancer. Prospective and retrospective outcomes study. Tertiary care institution. Participants in the longitudinal Outcomes Assessment Project whose head and neck cancer was treated with CRT between February 1, 2000, and March 1, 2007 (n = 104). Patients prospectively provided functional and health-related quality of life information, including data from the 1-year and most current follow-up visits. Medical records were reviewed to determine toxicity and survival rates. Well-defined acute and late toxicities; functional outcomes (diet, dentition, tracheostomies); head and neck cancer-specific, general health, and depression outcomes; and survival rates. Most patients had oropharyngeal or laryngeal tumors (87.5%) and advanced-stage disease (75.0%). Approximately one-half had hematologic toxicities and toxicity-related treatment delays. Approximately one-quarter had neurotoxicities and/or ototoxicites, moist desquamation, pneumonia, nausea and vomiting requiring hospitalization or intravenous fluids, dehydration or malnutrition requiring hospitalization, and mild or moderate fever. Although patients receiving the current intensity-modulated radiation therapy (IMRT) protocol using the Pinnacle(3) planning system had more toxicity-related treatment delays, they had fewer toxicities and better functional and health-related quality of life outcomes compared with those receiving conventional lateral opposing-field radiation or the initial IMRT protocol using the Best nomos PEACOCK planning system. Patients receiving CRT experience a substantial number of treatment-related adverse events, primarily affecting oropharyngeal and laryngeal function, with improvement noted for the current IMRT protocol. Improving dental prosthetic rehabilitation and including evaluations with speech and swallowing pathologists before and during treatment may enhance patient outcomes.