High-dose Clinical Target Volume Research Articles

Uncovering the Armpit of Axillary SBRT

The growing use of stereotactic body radiotherapy (SBRT) in metastatic cancer has led to applications in new and unique anatomic locations, highlighting the importance of effective, safe, reproducible treatment delivery. The objective of this study was to review our institutional SBRT experience for axillary metastases (AM), focusing on outcomes, safety and process. In this ethics approved single-institution retrospective review, patients treated with SBRT to AM from 2014-2022 had tumor, treatment planning, and dosimetric variables abstracted. Toxicity was assessed per Common Terminology for Adverse Events V5.0. Cumulative incidence functions were used to estimate the incidence of local failure (LF), with death as competing risk. Kaplan-Meier method was used to estimate progression-free (PFS) and overall survival (OS). We analyzed 37 patients with 39 AM who received SBRT. Patients were predominantly female (60%), Eastern Cooperative Oncology Group performance status 0-1 (62%), and elderly (median age: 72), with a median follow-up of 14.6 months. Common primary sites included breast (n = 16, 43%), skin (n = 7, 19%), and lung (n = 5, 14%). Treatment indication included oligoprogression (n = 18, 46%), oligometastases (n = 14, 36%) and symptomatic progression (n = 7, 18%). A minority had prior overlapping radiation (n = 7, 18%) or regional surgery (n = 4, 11%), while most had prior systemic therapy (n = 26, 70%). Significant heterogeneity in simulation, planning and treatment was identified. Immobilization included 5-point thermoplastic mask (n = 12, 32%), Vacloc (n = 12, 32%) arms-up thorax bag (n = 11, 30%). 4-D CT scans were obtained in 46%, MR simulation in 21%, and intravenous contrast in 10%. Median dose was 40 Gy (interquartile range (IQR): 35-40) in 5 fractions, (BED10 = 72 Gy), over a median of 12 days (IQR: 9-14). Seventeen cases (44%) utilized a low-dose elective volume to cover remaining axilla; 14% used a high dose clinical target volume. Median planning target volume margin was 5mm (range: 3-10mm), and plans were generated with 5 different dose constraint protocols. At first radiographic assessment, 87% had partial or complete response, with a single progression. Of symptomatic patients (n = 14), 57% had complete symptom resolution and 21% had improvement. One and 2-year LF rate were 19% and 31%, respectively. Median OS was 21.0 months (95% [Confidence Interval (CI)] 17.3-not reached) and median PFS was 7.0 months (95% [CI] 4.3-11.3). Acute and late toxicities were uncommon, with two grade 3 events (1 plexopathy in a case with tumor involving brachial plexus, 1 skin ulceration) identified, and no grade 4/5. In this series of AM SBRT, low rates of toxicity, and good rates of LF and symptom improvement were observed. As treatment was delivered with a variety of individual treatment differences, an institutional protocol is under development to standardize technique, optimize efficiency and improve evaluability.

Why subclinical involvement is prescribed the same high dose as gross tumor volume: A study on high-dose clinical target volume in intensity-modulated radiotherapy plan of nasopharyngeal carcinoma.

Most nasopharyngeal carcinoma (NPC) protocols define primary gross tumor volume (GTVnx) plus a range from 2 to 5 mm as the high-dose clinical target volume (hd-CTV). However, in China, hd-CTV is defined as GTVnx plus 0 mm. A total of 40 patients with newly diagnosed nonmetastatic NPC (T1-T4 ten cases each) treated with IMRT were consecutively enrolled. Real and virtual treatment plans were designed according to the definitions of hd-CTV recommended by China and Radiation Therapy Oncology Group (RTOG), respectively. The hd-CTV in China was significantly smaller than that of RTOG. Exposure doses to 5 mm subclinical involvement and OARs as well as NTCP in the China treatment plan were significantly lower than those of RTOG. It could be recommended to divide the hd-CTV into GTV and subclinical target volume and to prescribe different doses for the GTV and subclinical involvement in the IMRT plan of NPC.

Neoadjuvent androgen deprivation for seminal vesicle reduction: The optimal portion of seminal vesicle included in the high-dose CTV in localized prostate cancer radiotherapy

ObjectiveTo clarify the length and volume reduction of seminal vesicles (SVs) after neo-adjuvant hormonal therapy (NHT), in order to help contour the optimal SV included into high-dose clinical target volume (CTV) for radiotherapy in intermediate- and high-risk patients. MethodsMR images both before and after NHT (5.3 ​± ​2.2 months) were collected from thirty-one patients with cT2-4N0M0 prostate cancer. SV volume was measured in axial T1WI, while SV length was obtained in a reconstructed oblique coronary plane through its long axial from a 3D sequence. ResultsSVs showed evident reduction both in length and volume (length: median 12.1%, range 4.0%–28.0%; volume: median 39.9%, range 9.4%–66.2%). For SVs with and without MR detected involvement, length shortening were (16.7 ​± ​4.8)% and (11.1 ​± ​4.4)% (P ​< ​0.001); for involved SVs and lesions, volume reduction were (41.0 ​± ​16.0)% and (66.3 ​± ​14.4)%, respectively (P ​< ​0.001), both indicating a more sensitive response to NHT of the involved portion than normal SV. ConclusionsBoth volume and length of the SV will be reduced after receiving NHT. Besides, the invaded segments shrink more than normal SV tissue, indicating that SV portion included within the CTV can be reduced.

Comparing biological effectiveness guided plan optimization strategies for cranial proton therapy: potential and challenges

BackgroundTo introduce and compare multiple biological effectiveness guided (BG) proton plan optimization strategies minimizing variable relative biological effectiveness (RBE) induced dose burden in organs at risk (OAR) while maintaining plan quality with a constant RBE.MethodsDose-optimized (DOSEopt) proton pencil beam scanning reference treatment plans were generated for ten cranial patients with prescription doses ≥ 54 Gy(RBE) and ≥ 1 OAR close to the clinical target volume (CTV). For each patient, four additional BG plans were created. BG objectives minimized either proton track-ends, dose-averaged linear energy transfer (LETd), energy depositions from high-LET protons or variable RBE-weighted dose (DRBE) in adjacent serially structured OARs. Plan quality (RBE = 1.1) was assessed by CTV dose coverage and robustness (2 mm setup, 3.5% density), dose homogeneity and conformity in the planning target volumes and adherence to OAR tolerance doses. LETd, DRBE (Wedenberg model, α/βCTV = 10 Gy, α/βOAR = 2 Gy) and resulting normal tissue complication probabilities (NTCPs) for blindness and brainstem necrosis were derived. Differences between DOSEopt and BG optimized plans were assessed and statistically tested (Wilcoxon signed rank, α = 0.05).ResultsAll plans were clinically acceptable. DOSEopt and BG optimized plans were comparable in target volume coverage, homogeneity and conformity. For recalculated DRBE in all patients, all BG plans significantly reduced near-maximum DRBE to critical OARs with differences up to 8.2 Gy(RBE) (p < 0.05). Direct DRBE optimization primarily reduced absorbed dose in OARs (average ΔDmean = 2.0 Gy; average ΔLETd,mean = 0.1 keV/µm), while the other strategies reduced LETd (average ΔDmean < 0.3 Gy; average ΔLETd,mean = 0.5 keV/µm). LET-optimizing strategies were more robust against range and setup uncertaintes for high-dose CTVs than DRBE optimization. All BG strategies reduced NTCP for brainstem necrosis and blindness on average by 47% with average and maximum reductions of 5.4 and 18.4 percentage points, respectively.ConclusionsAll BG strategies reduced variable RBE-induced NTCPs to OARs. Reducing LETd in high-dose voxels may be favourable due to its adherence to current dose reporting and maintenance of clinical plan quality and the availability of reported LETd and dose levels from clinical toxicity reports after cranial proton therapy. These optimization strategies beyond dose may be a first step towards safely translating variable RBE optimization in the clinics.

Single-institution clinical experience using robust intensity modulated proton therapy in chordoma and chondrosarcoma of the mobile spine and sacrum: Feasibility and need for plan adaptation

BackgroundDue to its specific physical characteristics, proton irradiation is especially suited for irradiation of chordomas and chondrosarcoma in the axial skeleton. Robust plan optimization renders the proton beam therapy more predictable upon individual setup errors. Reported experience with the planning and delivery of robustly optimized plans in chordoma and chondrosarcoma of the mobile spine and sacrum, is limited. In this study, we report on the clinical use of robustly optimized, intensity modulated proton beam therapy in these patients. MethodsWe retrospectively reviewed patient, treatment and acute toxicity data of all patients with chordoma and chondrosarcoma of the mobile spine and sacrum, treated between 1 April 2019 and 1 April 2020 at our institute. Anatomy changes during treatment were evaluated by weekly cone-beam CTs (CBCT), supplemented by scheduled control-CTs or ad-hoc control-CTs. Acute toxicity was scored weekly during treatment and at 3 months after therapy according to CTCAE 4.0. Results17 chordoma and 3 chondrosarcoma patients were included. Coverage of the high dose clinical target volume was 99.8% (range 56.1–100%) in the nominal and 80.9% (range 14.3–99.6%) in the voxel-wise minimum dose distribution. Treatment plan adaptation was needed in 5 out of 22 (22.7%) plans. Reasons for plan adaptation were either reduced tumor coverage or increased dose to the OAR. ConclusionsRobustly optimized intensity modulated proton beam therapy for chordoma and chondrosarcoma of the mobile spine is feasible. Plan adaptations due to anatomical changes were required in approximately 23 percent of treatment courses.

Improvement in Dysphagia Outcomes Following Clinical Target Volume Reduction in the De-ESCALaTE Study

AimsThe De-ESCALaTE study showed an overall survival advantage for the administration of synchronous cisplatin chemotherapy with radiotherapy in low-risk oropharyngeal cancer when compared with synchronous cetuximab. During the trial, a radiotherapy quality assurance protocol amendment permitted centres to swap from the original radiotherapy contouring protocol (incorporating the whole oropharynx into the high-dose clinical target volume (CTV); anatomical protocol) to a protocol that incorporated the gross tumour volume with a 10 mm margin into the CTV (volumetric protocol). The purpose of this study was to examine both toxicity and tumour control related to this protocol amendment. Materials and methodsOverall survival and recurrence at 2 years were used to compare tumour control in the two contouring cohorts. For toxicity, the cohorts were compared by both the number of severe (grades 3–5) and all grades acute and late toxicities. In addition, quality of life and swallowing were compared using EORTC-C30 and MD Anderson Dysphagia Inventory, respectively. ResultsOf 327 patients included in this study, 185 were contoured according to the anatomical protocol and 142 by the volumetric protocol. The two cohorts were well balanced, with the exception of significantly more patients in the anatomical cohort undergoing prophylactic feeding tube insertion (P < 0.001). With a minimum of 2 years of follow-up there was no significant difference in overall survival or recurrence between the two contouring protocols. Similarly, there was no significant difference in the rate of reported severe or all grades acute or late toxicity and no sustained significant difference in quality of life. However, there was a significant difference in favour of volumetric contouring in several domains of the MD Anderson Dysphagia Inventory questionnaire at 1 year, which persisted to 2 years in the dysphagia functional (P = 0.002), dysphagia physical (P = 0.009) and dysphagia overall function (P = 0.008) domains. ConclusionIn the context of the unplanned post-hoc analysis of a randomised trial, measurable improvement in long-term dysphagia has been shown following a reduction in the CTV. Further reductions in the CTV should be subject to similar scrutiny within the confines of a prospective study.

International Consensus Contouring Recommendations for Stereotactic Body Radiotherapy of Non-Spine Bone Metastases

Despite the increasing use of stereotactic body radiotherapy (SBRT) for non-spine bone metastases (NSBM), there are no established guidelines for clinical target volume (CTV) delineation. The objective of this study was to provide recommendations on CTV delineation based on international expert consensus contours. Eleven cases were contoured by nine international radiation oncologists with demonstrated expertise in NSBM SBRT via publications and/or clinical experience. Cases included metastases in long bones (femur, humerus), pelvic bones (ilium, ischium, acetabulum, pubic symphysis) and thoracic bones (rib, sternum, scapula, clavicle). For each case the gross tumor volume (GTV) was provided on the simulation CT scans, which were accompanied by corresponding MR imaging. Experts then contoured the CTV and completed a clinical survey. Agreement between expert CTV contours was analyzed with simultaneous truth and performance level estimation (STAPLE) using the kappa coefficient and with the Dice similarity coefficient (DSC), and summarized to establish contouring recommendations. All CTV contours were completed for each of the eleven cases. Six experts used a single dose level, while 3 used a two-dose level (high dose and low dose) simultaneous integrated boost (SIB) technique. For the SIB cases, only the high dose CTV was used for contour analysis. There was substantial agreement between expert contours across cases with a mean and median kappa measure of 0.72 and 0.71 (range, 0.61-0.86), respectively. The mean and median DSC values were 0.77 and 0.79 (range, 0.67-0.87), respectively. Consensus CTV contouring recommendations consist of: 1) A ≤5mm intraosseous ± ≤5mm extraosseous margin beyond the GTV; 2) An extraosseous CTV margin should be strongly considered in cases of associated soft tissue disease and/or significant cortical bone disruption; 3) All CTVs should be manually modified to spare uninvolved joint spaces and organs-at-risk while respecting natural anatomical barriers (e.g. peritoneal cavity, pleura). Consensus CTV contouring recommendations for NSBM SBRT were established based on analysis of international expert consensus contours with a high level of agreement. Detailed quantitative margin analysis in three-dimensions is ongoing to define the optimal extent of CTV margins. Until prospective clinical data are available to inform patterns of failure, these recommendations may serve as guiding principles for treating physicians.

The impact of tongue-deviating and tongue-depressing oral stents on long-term radiation-associated symptoms in oropharyngeal cancer survivors

ObjectivesTo evaluate whether the use of oral stents during intensity modulated radiation therapy (IMRT) for oropharyngeal cancer (OPC) is associated with long-term patient reported symptoms. Materials and methodsData was obtained from a prospective observational study of disease-free head and neck cancer survivors. Radiation-associated patient reported symptoms were assessed using the MD Anderson Symptom Inventory Head and Neck module (MDASI-HN). Scores of ≥5 (11-point Likert scale, 0-10) were considered moderate/severe. Stratification was performed regarding IMRT volume (uni- versus bilateral neck) and stent utilization, with non-parametric analyses between groups. Results462 OPC survivors formed the cohort (54% tonsil, 46% base of tongue primaries). A tongue-deviating stent was used in 17%, tongue-depressing stent in 46%, and no stent in 37%. Median prescribed dose to the high dose clinical target volume was 66.0 Gy. Median follow-up from RT to MDASI-HN assessment was 68 months. Twenty percent had received unilateral neck RT (all had tonsil primaries), in whom a significant improvement in the proportion of patients with moderate/severe taste impairment (2% vs. 15%, p = 0.047) and lack of appetite (0% vs. 9%, p = 0.019) was associated with the use of tongue-deviating stents compared to no oral stent. In those who had received bilateral neck RT, a significant improvement in the proportion of patients with moderate/severe difficulty swallowing/chewing was associated with use of a tongue-depressing stent (21% vs. 31% without oral stent, p = 0.013). ConclusionDisease-site specific select use of oral stents during IMRT was associated with reduced long-term patient reported symptoms in OPC survivors.

An in silico comparative planning study investigating the predicted benefit of dysphagia-optimised volumetric arc therapy (Do-VMAT), relative to standard VMAT (S-VMAT), to reduce radiotherapy-associated dysphagia (RAD) in oropharyngeal cancers (OPC).

e18540 Background: RAD is a significant treatment-related functional morbidity in OPC and is associated with irradiation of the pharyngeal constrictor muscle (PCM). This study investigated whether a novel PCM-sparing Do-VMAT technique reduced the risk of RAD, compared to S-VMAT. Methods: Twenty OPC patients who previously underwent radiotherapy (RT) to bilateral neck were selected for this retrospective study. For each patient, S-VMAT and Do-VMAT plans were created. In both arms, the mucosal and nodal tumour received 65 Gy while the remaining oropharynx and at-risk nodal levels received 54 Gy; delivered in 30 fractions over 6 weeks. For Do-VMAT, a mandatory mean dose constraint of &lt; 50 Gy to the volume of the combined superior (SPCM) and middle PCM (MPCM) together with an optimal dose constraint of &lt; 20 Gy to the volume of inferior PCM (IPCM), lying outside the high-dose clinical target volume, were additionally defined and optimised to minimise PCM dose. Normal tissue complication probabilities for physician-scored RAD at 6 months (RAD6M) were determined as per the model by Christianen et al in which the 2 variables were mean dose to SPCM and supraglottic larynx (SGL). Statistical analysis was performed using paired t tests. Results: All plans had adequate target volume coverage, and dose to critical organs were within acceptable parameters. Dose to the parotid and submandibular glands were similar between the 2 RT techniques. The mean integral dose was 110.8 Gy-litre (standard deviation 17.1) with S-VMAT and 103.4 Gy-litre (15.4) with Do-VMAT, p &lt; 0.001. With Do-VMAT, the average of the mean dose to PCM, SPCM, MPCM, IPCM, and SGL were 9.3 Gy (1.4), 4.7 Gy (1.7), 7.4 Gy (3.6), 22.7 Gy (4.1), and 2.6 Gy (2.3) respectively lower than S-VMAT (p &lt; 0.001 for all). The mean predicted risk for RAD6M was 31.0 % (4.4) with S-VMAT, and 23.9 % (3.8) with Do-VMAT, p &lt; 0.001. The absolute reduction in estimated toxicity risk with Do-VMAT was &gt; 5 %, the minimally clinically important difference, in every patient. Conclusions: Do-VMAT demonstrated clinically relevant reductions in the predicted risk of RAD, compared to S-VMAT, by reducing dose to the PCM in OPC. The clinical benefits of Do-VMAT is being prospectively evaluated in DARS (CRUK/14/014), a randomised phase III study.

Prospective observational evaluation of radiation-induced late taste impairment kinetics in oropharyngeal cancer patients: Potential for improvement over time?

Background and purposeTaste impairment is a common radiation-induced toxicity in head and neck cancer (HNC) patients acutely. However, data on the potential for recovery and the time dependent course of late taste impairment are limited. Materials and methodsAs part of an IRB-approved observational prospective study, HNC patients underwent serial surveys including the MD Anderson Symptom Inventory - Head and Neck module (MDASI-HN). For our analysis, we extracted MDASI-HN taste item results from oropharyngeal cancer patients treated with intensity-modulated radiotherapy or volumetric modulated arc therapy and at least two taste assessments after ≥1 year from end of radiotherapy (RT). Results1214 MDASI taste items from 326 patients between 1 and 13 years post-RT were included. Median prescribed dose to the high-dose clinical target volume (CTV1) was 66.0 Gy, with 180 patients (55%) receiving chemotherapy. Taste markedly improved in the first years from end of RT, but plateaued after year 5. In patients with taste assessment in subsequent years, a significant reduction in taste impairment was found from the second to the third year (p = 0.001) and tended towards significance from the third to the fourth year (p = 0.058). Multivariate analysis revealed treatment site as significant factor in the sixth year from RT and CTV1 dose and age in the seventh year. ConclusionRadiation-induced taste impairment may improve over an extended time interval, but becomes relatively stable from year 5 post-RT. Direct characterization of RT-induced taste impairment and the calculation of normal tissue complication probability should include consideration of the time-dependent course in taste recovery.

Evaluation of replanning in intensity-modulated proton therapy for oropharyngeal cancer: Factors influencing plan robustness

The head and neck (H&N) region is frequently replanned during intensity-modulated proton therapy (IMPT), but replanning disrupts clinical workflow and presents additional burden on patients. The purpose of this study was to establish a standard treatment planning approach to minimize H&N replanning by identifying a correlation between dosimetric variables and replan frequency. In a retrospective study of 27 bilateral oropharyngeal cancer patients treated with IMPT at a single institution, cases were evaluated using Fisher's exact tests and logistic regression for a significant relationship between replan frequency and the following variables: beam number, clinical target volume (CTV) coverage, presence of dental fillings, and robustness. The reason and timing for replan initiation, and patient immobilization was also recorded to identify trends. Results suggested that beam number, CTV coverage, presence of dental fillings, and the initial robustness curve on the high-dose CTV did not individually contribute to replanning frequency. Setup variation in the soft tissue of the neck was the most prominent reason for replanning. A lack of correlation between the number of replans and the studied dosimetric variables highlights the necessity of verification CT and adaptive replanning in IMPT of H&N cancer. Departments may therefore benefit from a methodical replan workflow. One development showing potential to enhance clinical replan processes is machine learning-based automatic adaptive replanning.

Developing a Novel Machine Learning-Based Classification Scheme for Predicting SPCs in Breast Cancer Survivors.

Due to the high effectiveness of cancer screening and therapies, the diagnosis of second primary cancers (SPCs) has increased in women with breast cancer. The present study was conducted to develop a novel machine learning–based classification scheme for predicting the risk factors of SPCs in breast cancer survivors. The proposed scheme was based on the XGBoost classifier with the following four comparable strategies: transformation, resampling, clustering, and ensemble learning, to improve the training balanced accuracy. Results suggested that the best prediction accuracy for an empirical case is the XGBoost associated with the strategies of resampling and clustering. The experimental results showed that age, sequence of radiotherapy and surgery, surgical margins of the primary site, human epidermal growth factor, high-dose clinical target volume, and estrogen receptors are relatively more important risk factors associated with SPCs in patients with breast cancer. These risk factors should be monitored for the early detection of breast cancer. In conclusion, the proposed scheme can support the important influence of personality and clinical symptom representations in all phases of the primary treatment trajectory. Our results further suggested that adaptive machine learning techniques require the incorporation of significant variables for optimal predictions.

Quality Assurance Peer Review of Head and Neck Contours in a Large Cancer Centre via a Weekly Meeting Approach

AimsTo assess the impact of weekly scheduled peer review of head and neck contours for definitive and adjuvant radiotherapy cases based on rates of recommended changes. Materials and methodsRetrospective analysis of a prospective database. Recommended changes were prospectively classified as ‘major’ (change in gross tumour volume and/or high-dose clinical target volume, dose/fractionation) or ‘minor’ (change in intermediate or elective dose clinical target volumes or organs at risk). Univariate analysis to explore associations between recommended changes and tumour site/stage and radical/adjuvant indication. ResultsIn total, 307/375 (82%) head and neck cases treated with volumetric-modulated arc therapy were prospectively peer reviewed over a 12-month period; 195 (64%) cases received definitive and 112 (36%) received adjuvant radiotherapy. Overall, 43/307 (14.0%) changes were recommended within the peer review meetings. This comprised 27/307 (8.8%) major changes and 16/307 (5.2%) minor changes; 33/43 (77%) changes were in the clinical target volume. Rates of recommended changes were significantly higher for adjuvant versus definitive radiotherapy (odds ratio 2.26, P = 0.014) and for larynx compared with oropharynx (odds ratio 3.02, P = 0.02). There was no overall correlation between clinician experience and rates of change (P = 0.62). ConclusionRoutine weekly meeting contour-based peer review resulted in a number of major and minor changes to treatment. Compliance was high. Peer review was potentially beneficial for all tumour sites/stages/indications and any degree of clinician experience.

Local Failure Rate in Oropharyngeal Carcinoma Patients Treated with Intensity-modulated Radiotherapy Without High-dose Clinical Target Volume.

Purpose: Our purpose was to evaluate whether omitting high-dose clinical target volume radiation (CTV-HD) around the gross tumor volume (GTV) in patients with oropharyngeal squamous cell carcinoma (OSCC) treated with intensity-modulated radiotherapy (IMRT) was associated with increased local failure.Methods and materials: Patients diagnosed with stage I to stage IV OSCC between December 2004 and April 2017 were retrospectively reviewed. All patients were treated with radical radiotherapy using IMRT, with or without neoadjuvant or concurrent chemotherapy. In accordance with institution guidelines, CTV-HD was not used. Local failure was defined as disease persistence or reappearance at the primary tumor site. When primary failure was documented, the computed tomography/positron emission tomography (CT/PET) scan that showed primary failure was fused with the original treatment scan. Each recurrent tumor was contoured to evaluate the pattern of recurrence. Recurrences were categorized as in-field, marginal, or out-of-field if >95%, 20%-95%, or <20% of the recurrent tumor volume, respectively, was encompassed by the 95% high-dose prescription isodose line of the original treatment plan. We then determined whether omitting CTV-HD was associated with increased locoregional failure.Results: A total of 272 patients with OSCC were assessed. The median follow-up from initial treatment was 43 months (range: 3-194 months). Seven patients were lost to follow-up. The overall five-year survival rate was 87%. The three- and five-year disease-free survival rates were 86% and 83%, respectively. Forty-one patients had 53 treatment failures (16 were local, eight were regional, and 29 were distant; some patients had treatment failures in multiple locations). Fourteen (87.5%) of the local recurrences were in-field, one (6.25%) was marginal, and one (6.25%) was out-of-field.Conclusion: Our analysis of patients with oropharyngeal cancer suggests that local failure is mostly in-field and potentially due to radioresistance, rather than a marginal miss of the tumor. It suggests that omitting CTV-HD is feasible and safe.

Partial Laryngeal IMRT for T2N0 Glottic Cancer: Impact of Image Guidance and Radiation Therapy Intensification

To assess the impact of the radiation therapy (RT) regimen and image guidance (image guided radiation therapy [IGRT]) protocol on local control (LC) for T2N0 glottic cancer treated with partial laryngeal intensity modulated radiation therapy (IMRT). All patients with T2N0 glottic cancer treated with IMRT from 2006 to 2013 at a single institution were retrospectively reviewed. The gross tumor volume (GTV), delineated from endoscopic and/or radiologic findings, was expanded 0.5cm for the high-dose clinical target volume and an additional 0.5cm for the lower-dose clinical target volume (total of 1.0cm from GTV).The planning target volume margin was 0.5cm radially and 1cm superiorly and inferiorly. RT regimens evolved from hypofractionated IMRT (RT-hypo, 60Gy in 25 fractions over a period of 5weeks) to moderately accelerated IMRT (RT-acc, 66-70Gy in 33-35 fractions over a period of 5.5-6weeks) since 2010. The IGRT matching surrogate changed from cervical vertebral bone (IGRT-bone) to laryngeal soft tissue (IGRT-larynx) in2008. LC was compared between 3 sequential cohorts: RT-hypo/IGRT-bone, RT-hypo/IGRT-larynx, and RT-acc/IGRT-larynx. Multivariable analysis assessed the relative impact of RT regimen and IGRT technique on local failure separately. Among 139 eligible patients (median follow-up period, 5.03years [range, 0.8-10.5years]), we identified 28 local, 6 regional, and 2 distant failures. A higher 3-year LC rate was observed for RT-acc/IGRT-larynx (89% [95% CI: 78%-95%]) versus RT-hypo/IGRT-larynx (80% [95% CI: 54%-91%]) and RT-hypo/IGRT-bone (70% [95% CI: 53%-80%]) (P=.02).Multivariable analysis adjusted for GTV (in cubic centimeters) and smoking status confirmed that IGRT-larynx versus IGRT-bone (hazard ratio, 0.40; P=.019) and RT-acc versus RT-hypo (hazard ratio, 0.34; P=.012) both reduced the risk of local failure. This single-institution cohort study shows a high LC rate (89%) for T2N0 glottic cancer following moderately accelerated partial laryngeal IMRT with daily laryngeal soft tissue matching IGRT. These results appear to represent an improvement attributable to changes in both IGRT matching and dose delivered, but their independent significance is unknown and further confirmation in a larger cohort is warranted.

An impact of pelvic MRI (PMRI) to radiotherapy (RT) target volumes definition in prostate cancer patients (pts).

78 Background: PMRI is a standard pre-RT evaluation procedure in pts with intermediate and high-risk prostate cancer. We conducted a retrospective study to evaluate an influence of PMRI to delineation of RT clinical target volume (CTV). Methods: Medical records of prostate cancer pts treated with intensity-modulated RT (IMRT) in single institution retrieved and examined retrospectively. Initial risk group affiliation was defined using D'Amico method. PMRI reports of pts with intermediate and high-risk prostate cancer were reviewed and risk group affiliation was re-defined in regards of T- and N-stage. IMRT treatment plans were re-assessed. In regards to PMRI T-stage, extra-capsular extension (ECE) and seminal vesicles invasion (SVI) were included to high-dose CTV. Pelvic lymph nodes (PLN) were planned to treat in all high-risk pts. PLN considered pathological by PMRI were included to separate CTV to receive RT dose higher than unaffected PLN stations. Results: Between 2008 and 2014, 169 pts with intermediate and high-risk prostate cancer underwent PMRI at around 1 month before commencing IMRT. Initially, 89 pts were affiliated to intermediate-risk and 80 to high-risk group. In general, PTV-changes based on PMRI data required in 77 pts (45.5%). Thirty seven of 89 intermediate-risk pts (41.6%) have been switched to high-risk group, necessitating irradiation of PLN. ECE and SVI were included to high-dose CTV in 64 (37.8%) and 29 pts (17.2%) respectively. PLN were thought pathological in 10 pts (5.9%), which demanded contouring of a separate CTV. Conclusions: In our series PMRI-scans had a significant impact on RT target coverage decision in pts with intermediate and high-risk prostate cancer.

Patterns of Failure after Intensity-modulated Radiotherapy in Head and Neck Squamous Cell Carcinoma using Compartmental Clinical Target Volume Delineation

AimsTo determine the pattern of disease recurrence in non-nasopharyngeal head and neck squamous cell carcinoma (HNSCC) patients treated with radical intensity-modulated radiotherapy (IMRT) with or without chemotherapy, and to correlate the sites of locoregional recurrence with radiotherapy target volumes. Materials and methodsIn total, 136 patients treated with radical IMRT with or without chemotherapy between 2008 and 2011 for non-nasopharyngeal HNSCC were retrospectively identified. A compartmental approach to clinical target volume (CTV) delineation was routinely utilised during this period and IMRT was delivered using a 5–7 angle step and shoot technique. Locoregional recurrences were reconstructed on the planning computed tomography scan by both deformable image coregistration and by visual assessment, and were analysed in relation to target volumes and dosimetry. ResultsThe median follow-up was 31 (range 3–53) months. Two year local control, regional control, disease-free survival, distant metastasis-free survival and overall survival were 86, 93, 78, 89 and 79%, respectively. One hundred and twenty of 136 (88%) patients achieved a complete response to treatment and 7/120 (6%) have subsequently had a locoregional recurrence. Analysis of these recurrences revealed five to be infield; one to be marginal to the high-dose CTV; one to be out-of-field. Overall the marginal/out-of-field recurrence rate was 2/136 (1.5%). ConclusionsIMRT utilising a compartmental approach to CTV delineation was associated with a low rate of marginal/out-of-field recurrence.

Co-registration of cone beam CT and planning CT in head and neck IMRT dose estimation: a feasible adaptive radiotherapy strategy

To investigate if cone beam CT (CBCT) can be used to estimate the delivered dose in head and neck intensity-modulated radiotherapy (IMRT). 15 patients (10 without replan and 5 with replan) were identified retrospectively. Weekly CBCT was co-registered with original planning CT. Original high-dose clinical target volume (CTV1), low-dose CTV (CTV2), brainstem, spinal cord, parotids and external body contours were copied to each CBCT and modified to account for anatomical changes. Corresponding planning target volumes (PTVs) and planning organ-at-risk volumes were created. The original plan was applied and calculated using modified per-treatment volumes on the original CT. Percentage volumetric, cumulative (planned dose delivered prior to CBCT + adaptive dose delivered after CBCT) and actual delivered (summation of weekly adaptive doses) dosimetric differences between each per-treatment and original plan were calculated. There was greater volumetric change in the parotids with an average weekly difference of between -4.1% and -27.0% compared with the CTVs/PTVs (-1.8% to -5.0%). The average weekly cumulative dosimetric differences were as follows: CTV/PTV (range, -3.0% to 2.2%), ipsilateral parotid volume receiving ≥26 Gy (V26) (range, 0.5-3.2%) and contralateral V26 (range, 1.9-6.3%). In patients who required replan, the average volumetric reductions were greater: CTV1 (-2.5%), CTV2 (-6.9%), PTV1 (-4.7%), PTV2 (-11.5%), ipsilateral (-10.4%) and contralateral parotids (-12.1%), but did not result in significant dosimetric changes. The dosimetric changes during head and neck simultaneous integrated boost IMRT do not necessitate adaptive radiotherapy in most patients. Our study shows that CBCT could be used for dose estimation during head and neck IMRT.

SU-E-J-209: Dosimetric Benefits of Replanning for IMRT Treatment of Head and Neck Cancer

Purpose: To evaluate the dosimetric benefit of replanning during the course of intensity modulated radiotherapy (IMRT) for head-and-neck cancer patients. Methods: The study included 30 patients who had at least one replan due to weight loss, tumor growth, swelling, or positioning issues. They were prescribed to receive between 60 and 70 Gy with simultaneous integrated boost using multiple-field IMRT or volumetric modulated arc therapy. The original plan of each patient was recalculated on the computed tomography (CT) set acquired for replanning. MIM Software (Cleveland, OH) was used to rigidly align the original and the new CT to the same coordinate system, matching the high-dose clinical target volume (CTV). These recalculations represent the scenario where the treatment continues with a new setup but the same treatment plan is used. Results: Without replanning, the mean near maximum dose (D2%) to the high-dose CTV was increased by 2.0%. The mean near minimum (D98%) doses to the high, intermediate, and low-dose CTVs were decreased by 5.1%, 4.0%, and 3.1% respectively. One patient could not meet the brainstem maximum dose (Dmax) constraint of 54 Gy. The mean parotid dose was increased by 1.8%. There was a weak correlation between the parotid dose and the change in parotid volume (correlation coefficient=−0.323, p=0.016). Setup variations between CT simulations caused 46% of the plans to exceed the spinal cord Dmax constraint of 45 Gy, and 22% of the plans to have hot spots exceeding 120% of the prescription dose. The replans were comparable to the original plans in target dose coverage, homogeneity, and critical structure doses. Replanning reduced the mean parotid dose by <0.7%. Conclusion: Replanning is important when the patient setup is notably different than the original simulation. When done in conjunction with image guidance before treatment delivery, it helps to ensure dosimetric objectives can be maintained.

Target Volume Definition for Intensity-modulated Radiotherapy after Induction Chemotherapy and Patterns of Treatment Failure after Sequential Chemoradiotherapy in Locoregionally Advanced Oropharyngeal Squamous Cell Carcinoma

AimsTo validate our approach to target volume definition for intensity-modulated radiotherapy (IMRT) after induction chemotherapy and to analyse the pattern of treatment failure in patients with locoregionally advanced oropharyngeal squamous cell carcinoma (SCC) after sequential chemoradiotherapy (SCRT). Materials and methodsWe studied all patients with locoregionally advanced oropharyngeal SCC treated with SCRT, definitive IMRT and no prior surgery between December 2004 and February 2010. SCRT consisted of three cycles of induction chemotherapy followed by IMRT with concurrent weekly chemotherapy. Our approach to IMRT tumour volume definition after induction chemotherapy was similar to recommendations from published clinical practice guidelines. Volumetric expansion was used to create the high-dose clinical target volume with a margin of 10 mm. The high-dose planning target volume (PTV) was treated to 65 Gy, whereas the prophylactic-dose PTV received 54 Gy over 30 fractions using the simultaneous integrated boost technique. The location and extent of each treatment failure was recorded, reconstructed on the planning computed tomography images and analysed using the dose distribution of the IMRT plan. ResultsFifty-two patients were included. The median follow-up was 32.2 months (range 5.0–67.1 months). There were seven local failures, no regional recurrences and one with distant disease. None of the patients required post-treatment neck dissection. All local failures were in-field and occurred within the high-dose PTV. There were no marginal recurrences. Actuarial recurrence-free, disease-specific and overall survival rates at 3 years were 83.9, 85.9 and 79.7%, respectively. ConclusionsThe absence of marginal recurrences validated the approach to IMRT target volume definition after induction chemotherapy proposed by clinical practice guidelines and practised at our institution. It suggested a lack of benefit with the use of larger geometric margins and additional anatomical expansion for the high-dose clinical target volume. SCRT resulted in excellent regional and distant disease control in patients with locoregionally advanced oropharyngeal SCC.