Sparing Intensity Modulated Radiation Therapy Research Articles

The evaluation of the feasibility of carotid sparing intensity modulated radiation therapy technique for comprehensive breast irradiation

PurposeTo investigate the feasibility of carotid sparing intensity modulated radiation therapy (CS-IMRT) to minimize the radiation dose to carotid arteries for comprehensive irradiation of breast cancer patients who have risk factors for atherosclerosis. The dose distribution of CS-IMRT technique and the conventional irradiation technique were also compared. Patients and methodsTen patients who were previously treated with comprehensive three-dimensional conformal radiation therapy (3DCRT) were selected. DICOM data were used to contour the carotid artery and to create the virtual CS-IMRT plans for each patient. 3DCRT and CS-IMRT plans were compared in terms of conformity index, homogeneity index, and the doses to organ at risk and carotid arteries. ResultsThe homogeneity and conformity indices were better with CS-IMRT plans compared to 3DCRT plan. The homogeneity index was 1.13 vs 1.11 (p=0.007) for 3DCRT and CS-IMRT and the conformity index was 0.96 vs 0.97 (p=0.006) for 3DCRT and CS-IMRT. The radiation dose to the carotid arteries were reduced by applying CS-IMRT without compromising the target volume coverage. When the carotid artery was considered as organ at risk for CS-IMRT planning, the median of V50 was decreased to 0% from 12.5% compared to 3DCRT plans (p=0.017). The median of the maximum dose to the carotid artery was decreased under 50Gy with CS-IMRT. ConclusionsCS-IMRT can significantly reduce the unnecessary radiation dose to the carotid arteries compared with conventional 3DCRT technique while maintaining target volume coverage. CS-IMRT technique can be considered for breast cancer patient with high risk of atherosclerosis.

Prophylactic exercises among head and neck cancer patients during and after swallowing sparing intensity modulated radiation: adherence and exercise performance levels of a 12-week guided home-based program

The background and purpose of this paper is to investigate adherence, exercise performance levels and associated factors in head and neck cancer (HNC) patients participating in a guided home-based prophylactic exercise program during and after treatment [swallowing sparing intensity modulated radiation therapy (SW-IMRT)]. Fifty patients were included in the study. Adherence was defined as the percentage of patients who kept up exercising; exercise performance level was categorized as low: ≤1, moderate: 1–2, and high: ≥2 time(s) per day, on average. Associations between 6- and 12-week exercise performance levels and age, gender, tumour site and stage, treatment, intervention format (online or booklet), number of coaching sessions, and baseline HNC symptoms (EORTC-QLQ-H&N35) were investigated. Adherence rate at 6 weeks was 70% and decreased to 38% at 12 weeks. In addition, exercise performance levels decreased over time (during 6 weeks: 34% moderate and 26% high; during 12 weeks: 28% moderate and 18% high). The addition of chemotherapy to SW-IMRT [(C)SW-IMRT] significantly deteriorated exercise performance level. Adherence to a guided home-based prophylactic exercise program was high during (C)SW-IMRT, but dropped afterwards. Exercise performance level was negatively affected by chemotherapy in combination with SW-IMRT.

Phase 1 Trial of Bone Marrow Sparing Intensity Modulated Radiation Therapy With Concurrent Cisplatin and Gemcitabine in Stage IB-IVA Cervical Cancer

Author(s): Mell, LK; Saenz, CC; Yashar, CM; McHale, MT; Einck, JP; Wright, ME; Noticewala, SS; Xu, R; Plaxe, SC; Mundt, AJ

ATLAS-Based Active Bone Marrow–Sparing Intensity Modulated Radiation Therapy for Cervical Cancer

Author(s): Li, N; Noticewala, SS; Williamson, CW; Shen, H; Sirak, I; Tarnawski, RR; Mahantshetty, UM; Moore, KL; Mell, LK

Phase 2 Multicenter Clinical Trial of Bone Marrow–Sparing Intensity Modulated Radiation Therapy With Concurrent Cisplatin for Stage IB-IVA Cervical Cancer

Author(s): Mell, LK; Sirak, I; Wei, L; Tarnawski, RR; Mahantshetty, UM; Yashar, CM; McHale, MT; Wright, ME; Pritz, J; Straube, W; Xu, R; Kasaova, L; Michalski, JM; Bosch, WR; Followill, DS; Schwarz, JK; Honerkamp-Smith, G; Leif, JL; Saenz, CC; Einck, JP; Koonings, PP; Harrison, TA; Khorprasert, C; Shi, M; Plaxe, SC; Mundt, AJ

Doses to Pelvic Bone Marrow from Intracavitary Brachytherapy in Carcinoma Cervix: A Dosimetric Study

Doses to Pelvic Bone Marrow from Intracavitary Brachytherapy in Carcinoma Cervix: A Dosimetric Study

Carotid sparing intensity modulated radiotherapy on early glottic cancer: preliminary study.

PurposeTo compare the dose distribution between carotid sparing intensity modulated radiotherapy (IMRT) and opposed lateral field technique (LAFT), and to determine the effects of carotid sparing IMRT in early glottic cancer patients who have risk factors for atherosclerosis.Materials and MethodsTen early glottic cancer patients were treated with carotid sparing IMRT. For each patient, the conventional LAFT plan was developed for comparison. IMRT and LAFT plans were compared in terms of planning target volume (PTV) coverage, conformity index, homogeneity index, and the doses to planning organ at risk volume (PRV) for carotid arteries, spinal cord and pharyngeal constrictor muscle.ResultsRecurrence was not observed in any patients during the follow-up period. V95% for PTV showed no significant difference between IMRT and LAFT plans, while V100% was significantly higher in the IMRT plan (95.5% vs. 94.6%, p = 0.005). The homogeneity index (11.6%) and conformity index (1.4) in the IMRT plan were significantly better than those in the LAFT plans (8.5% and 5.1, respectively) (p = 0.005). The median V5Gy (90.0%), V25Gy (13.5%), and V50Gy (0%) for carotid artery PRV in the IMRT plan were significantly lower than those in the LAFT plan (99.1%, 89.0%, and 77.3%, respectively) (p = 0.005).ConclusionOur study suggests that carotid sparing IMRT can significantly decrease the dose to carotid arteries compared to LAFT, and it would be considered for early glottic cancer patient with high risk of atherosclerosis.

Comparison of bone marrow sparing intensity modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT) in carcinoma of anal canal: a prospective study.

Chemoradiation (CRT) is the standard of care in anal canal carcinoma. CRT leads to suppression of iliac bone marrow (BM) leading to hematological toxicity. Intensity modulated radiation therapy (IMRT) technique can be used to decrease radiation dose to iliac BM and thus decrease haematological toxicity. This study aims to compare the haematological and gastrointestinal toxicity in BM sparing IMRT with three-dimensional conformal radiation therapy (3DCRT) in anal carcinoma patients. Twenty untreated, biopsy proven anal canal carcinoma (stages I-III) patients were randomized into IMRT and 3DCRT arm. All patients received CRT with 45 Gy in 25 fractions at 1.8 Gy/fraction and weekly concurrent inj. cisplatin and 5-FU. Patients were evaluated for acute haematological and gastrointestinal toxicity during treatment. Additional dosimetric comparison was made between the two groups. Incidence of worst hematological toxicity grade II (GII) and GIII was seen in 40% [4] vs. 30% [3] and 20% [2] vs. 0% [0] respectively, in 3DCRT and IMRT group. However these did not come as statistically significant (P=0.228). Incidence of worst gastrointestinal toxicity during treatment in terms of GII was 30% [3] vs. 50% [5] and GIII was 60% [6] vs. 0% [0] in 3DCRT and IMRT group respectively (P=0.010). Other parameters indicating better tolerance of treatment with IMRT arm than 3DCRT arm were lesser need for administration of parenteral fluid 10% [1] vs. 60% [6] (P=0.019); lesser need for blood transfusion 0% [0] vs. 20% [2] (P=0.060) in IMRT arm than in 3DCRT arm respectively. Patient requiring supportive care during treatment like need for anti-motility drugs and WHO. Step II analgesics also favored IMRT arm. Overall treatment time for Arm B (33.40 days) was less than what was seen in Arm A patients (36.8 days), although difference was not statistically significant (P=0.569). In terms of dosimetric analysis, arm B with the use of IMRT showed superiority over arm A with 3DCRT. The mean volume of bladder receiving ≥30 and 40 Gy respectively was 100% and 96% for group A (3DCRT) as compared to 68% and 31% for the group B (IMRT) (P<0.05). For bowel, although, the V30 and V40 for 3DCRT versus IMRT respectively were 51% and 27% vs. 27% and 13%, statistical significance was not reached (P>0.05). There was also less mean BM receiving ≥10 Gy (80.4%) and ≥20 Gy (65.6%) for group B using IMRT, than in 3DCRT (group A) were it was 91% and 73% respectively. Although for V10 it was significant (P=0.04), it did not reach statistical significance for the V20 (P=0.550). Preliminary outcomes suggest that BM sparing IMRT for anal canal cancers can decrease both haematological and gastrointestinal toxicity as compared to 3DCRT and thus CRT course can be completed effectively without treatment breaks.

A Phase II Study of Magnetic Resonance Imaging Guided Hematopoietical Bone Marrow Sparing Intensity Modulated Radiation Therapy With Concurrent Chemotherapy for Gastric Cancer

cohort, one patient suffered from allergy to paclitaxel, the rest eleven patients completed whole treatment schedule. However, a Grade 4 leukopenia and a Grade 3 thrombocytopenia were observed in the 3 patients of 4th level of 54Gy/1.8Gy/30f cohort. The MTD was 5 or 6 weekly cycles of paclitaxel 40 mg/m and cisplatin 20 mg/mconcurrent with 54 Gy of radiation therapy. After that, CTV was adjusted into upper borderline of the first thoracic vertebra to 3cm below tumor bed. No DLT was observed in the 12 patients in 60 Gy/2.0 Gy/30f cohort. One year overall survival was 81.8%. The volume of clinical target and the mean dose of stomach were significantly reduced because of revision (P Z 0.006, P Z 0.015). One patient had abdominal lymph nodes below celiac axis recurrence after target modification. Conclusion:Weekly cycle of paclitaxel and cisplatin was proven to be safe and efficacious with postoperative radiation of suitable extent of CTV for node-positive thoracic esophageal carcinoma. A Phase II study evaluating Dose Level 4 is ongoing. Author Disclosure: S. Yu: None. Z. Xiao: None. Z. Zhou: None. H. Zhang: None. C. Dongfu: None. Q. Feng: None. J. Liang: None.

Assessing the Potential Risk of Cardiac Toxicity With Esophageal Sparing Intensity Modulated Radiation Therapy for Locally Advanced Lung Cancer

Assessing the Potential Risk of Cardiac Toxicity With Esophageal Sparing Intensity Modulated Radiation Therapy for Locally Advanced Lung Cancer

Definition of Planning Target Volume Margins for Carotid Sparing Intensity Modulated Radiation Therapy for Early Glottis Cancer

Definition of Planning Target Volume Margins for Carotid Sparing Intensity Modulated Radiation Therapy for Early Glottis Cancer

Comparison of dose distributions hippocampus in high grade gliomas irradiation with linac-based imrt and volumetric arc therapy: a dosimetric study.

The aim of this study was to assess the feasibility of sparing contralateral hippocampus during partial brain radiotherapy in high grade gliomas. 20 previously treated patients were replanned to 60 Gy in 30 fractions with sparing intensity-modulated radiotherapy (IMRT) and volumetric modulated arctherapy (VMAT) using the following planning objectives: 100 % of PTV covered by 95% isodose without violating organs at risk (OAR) and hot spot dose constraints. For each, standard intensity-modulated radiotherapy (IMRT) plans were generated, as well as sparing IMRT and VMAT plans which spared contralateral (hemispheric cases) hippocampus. When the three plans were compared, there was equivalent PTV coverage, homogeneity, and conformality. Sparing IMRT significantly reduced maximum, mean, V20, V30 and V40 hippocampus doses compared with standart IMRT and VMAT (p < 0.05). VMAT significantly reduced maximum left lens and mean eye doses compared with standart IMRT and sparing IMRT (p < 0.05). Brainstem, chiasm, left and right optic nerves, right eyes and lens doses were similar. VMAT significantly reduced monitor units compared with standart IMRT and sparing IMRT (p < 0.05). It is possible to spare contralateral hippocampus during PBRT for high grade gliomas using IMRT. This approach may reduce late cognitive sequelae of cranial radiotherapy.

Carotid sparing intensity-modulated radiotherapy in early glottic cancers: A case of Maslow′s hammer?

Carotid sparing intensity-modulated radiotherapy in early glottic cancers: A case of Maslow′s hammer?

Submandibular gland-sparing radiation therapy for locally advanced oropharyngeal squamous cell carcinoma: patterns of failure and xerostomia outcomes.

BackgroundSaliva from submandibular glands (SMG) is necessary to minimize xerostomia. It is unclear whether SMG can be safely spared in patients undergoing bilateral neck radiotherapy for locally advanced oropharyngeal cancer without increasing the risk of marginal recurrence. We evaluated the outcomes of contralateral submandibular gland (cSMG) sparing intensity-modulated radiation therapy (IMRT).MethodsAll patients with stage III/IV oropharyngeal squamous cell carcinoma treated with bilateral neck IMRT from 2006–2012 at our institution were included. Appropriately selected patients with favorable primary tumor characteristics and no definite contralateral neck disease were treated with cSMG-sparing IMRT. Patterns of failure and xerostomia outcomes were retrospectively analyzed.Results114 patients were treated. 89% had stage IV disease and 89% received definitive radiation therapy. 76 patients (67%) received cSMG sparing IMRT. With a median follow-up of 30 months, there were 10 local, 9 regional, and 10 distant recurrences. 2-year overall survival was 86% and 2-year loco-regional control was 87%. In cSMG spared patients, the mean cSMG dose was 30.7 Gy. Late grade 2+ xerostomia was significantly reduced in the cSMG spared group compared to those without SMG sparing (6 months: 23% vs. 72%, 12 months: 6% vs. 41%, 24 months: 3% vs. 36%, all p < 0.0007). There were no peri-SMG marginal recurrences in the cSMG-spared cohort.ConclusionscSMG sparing IMRT did not increase marginal failures in this series of locally advanced oropharyngeal SCC patients. Xerostomia was significantly reduced in cSMG spared patients.

Evaluation of the Dosimetric Feasibility of Hippocampal Sparing Intensity-Modulated Radiotherapy in Patients with Locally Advanced Nasopharyngeal Carcinoma

PurposeThe objective of this study was to evaluate the dosimetric feasibility of using hippocampus (HPC) sparing intensity-modulated radiotherapy (IMRT) in patients with locally advanced nasopharyngeal carcinoma (NPC).Materials/MethodsEight cases of either T3 or T4 NPC were selected for this study. Standard IMRT treatment plans were constructed using the volume and dose constraints for the targets and organs at risk (OAR) per Radiation Therapy Oncology Group (RTOG) 0615 protocol. Experimental plans were constructed using the same criteria, with the addition of the HPC as an OAR. The two dose-volume histograms for each case were compared for the targets and OARs.ResultsAll plans achieved the protocol dose criteria. The homogeneity index, conformity index, and coverage index for the planning target volumes (PTVs) were not significantly compromised by the avoidance of the HPC. The doses to all OARs, excluding the HPC, were similar. Both the dose (Dmax, D2%, D40%, Dmean, Dmedian, D98% and Dmin) and volume (V5, V10, V15, V20, V30, V40 and V50) parameters for the HPC were significantly lower in the HPC sparing plans (p<0.05), except for Dmin (P = 0.06) and V5 (P = 0.12).ConclusionsIMRT for patients with locally advanced NPC exposes the HPC to a significant radiation dose. HPC sparing IMRT planning significantly decreases this dose, with minimal impact on the therapeutic targets and other OARs.

Safety of Submandibular Gland Sparing Intensity Modulated Radiation Therapy for Advanced Oropharyngeal Cancer: Definitive Management of Head-and-Neck Squamous Cell Carcinoma

Safety of Submandibular Gland Sparing Intensity Modulated Radiation Therapy for Advanced Oropharyngeal Cancer: Definitive Management of Head-and-Neck Squamous Cell Carcinoma

Hippocampal sparing radiotherapy for pediatric medulloblastoma: impact of treatment margins and treatment technique

We investigated how varying the treatment margin and applying hippocampal sparing and proton therapy impact the risk of neurocognitive impairment in pediatric medulloblastoma patients compared with current standard 3D conformal radiotherapy. We included 17 pediatric medulloblastoma patients to represent the variability in tumor location relative to the hippocampal region. Treatment plans were generated using 3D conformal radiotherapy, hippocampal sparing intensity-modulated radiotherapy, and spot-scanned proton therapy, using 3 different treatment margins for the conformal tumor boost. Neurocognitive impairment risk was estimated based on dose-response models from pediatric CNS malignancy survivors and compared among different margins and treatment techniques. Mean hippocampal dose and corresponding risk of cognitive impairment were decreased with decreasing treatment margins (P < .05). The largest risk reduction, however, was seen when applying hippocampal sparing proton therapy-the estimated risk of impaired task efficiency (95% confidence interval) was 92% (66%-98%), 81% (51%-95%), and 50% (30%-70%) for 3D conformal radiotherapy, intensity-modulated radiotherapy, and proton therapy, respectively, for the smallest boost margin and 98% (78%-100%), 90% (60%-98%), and 70% (39%-90%) if boosting the whole posterior fossa. Also, the distance between the closest point of the planning target volume and the center of the hippocampus can be used to predict mean hippocampal dose for a given treatment technique. We estimate a considerable clinical benefit of hippocampal sparing radiotherapy. In choosing treatment margins, the tradeoff between margin size and risk of neurocognitive impairment quantified here should be considered.

Stereotactic body radiation therapy planning with duodenal sparing using volumetric-modulated arc therapy vs intensity-modulated radiation therapy in locally advanced pancreatic cancer: A dosimetric analysis

Stereotactic body radiation therapy (SBRT) achieves excellent local control for locally advanced pancreatic cancer (LAPC), but may increase late duodenal toxicity. Volumetric-modulated arc therapy (VMAT) delivers intensity-modulated radiation therapy (IMRT) with a rotating gantry rather than multiple fixed beams. This study dosimetrically evaluates the feasibility of implementing duodenal constraints for SBRT using VMAT vs IMRT. Non–duodenal sparing (NS) and duodenal-sparing (DS) VMAT and IMRT plans delivering 25Gy in 1 fraction were generated for 15 patients with LAPC. DS plans were constrained to duodenal Dmax of<30Gy at any point. VMAT used 1 360° coplanar arc with 4° spacing between control points, whereas IMRT used 9 coplanar beams with fixed gantry positions at 40° angles. Dosimetric parameters for target volumes and organs at risk were compared for DS planning vs NS planning and VMAT vs IMRT using paired-sample Wilcoxon signed rank tests. Both DS VMAT and DS IMRT achieved significantly reduced duodenal Dmean, Dmax, D1cc, D4%, and V20Gy compared with NS plans (all p≤0.002). DS constraints compromised target coverage for IMRT as demonstrated by reduced V95% (p = 0.01) and Dmean (p = 0.02), but not for VMAT. DS constraints resulted in increased dose to right kidney, spinal cord, stomach, and liver for VMAT. Direct comparison of DS VMAT and DS IMRT revealed that VMAT was superior in sparing the left kidney (p<0.001) and the spinal cord (p<0.001), whereas IMRT was superior in sparing the stomach (p = 0.05) and the liver (p = 0.003). DS VMAT required 21% fewer monitor units (p<0.001) and delivered treatment 2.4 minutes faster (p<0.001) than DS IMRT. Implementing DS constraints during SBRT planning for LAPC can significantly reduce duodenal point or volumetric dose parameters for both VMAT and IMRT. The primary consequence of implementing DS constraints for VMAT is increased dose to other organs at risk, whereas for IMRT it is compromised target coverage. These findings suggest clinical situations where each technique may be most useful if DS constraints are to be employed.

Reduced Myelotoxicity in Pelvic Malignancies With Bone Marrow Sparing IMRT

Intensity Modulated radiation therapy (IMRT) decreases bowel and bladder toxicity. The current reported myelotoxicity rates are high (50-60%). Dose constraint recommendations for bone marrow for treatment planning were generated after retrospective review to decrease the incidence of myelotoxicity. This study was undertaken to prospectively utilize the currently available planning recommendations and assess the clinical outcomes of these patients. All patients treated with concurrent chemotherapy and radiation at a single institution for pelvic malignancies were prospectively included in the study. These included 49 consecutive patients treated between 6/2010- 12/2011 (19 Rectal cancers, 9 anal cancers and 21 cervical cancers). All patients received concurrent chemotherapy. Dose constraints for bladder, bowel, femoral heads and bone marrow were prospectively utilized in planning according to institutional protocol for all patients. Marrow contours included all bones in the field of treatment. Bone marrow was constrained to V10< 95%, V20< 80% and V30< 64%. Weekly hematologic toxicity data was collected during radiation treatment and graded according to RTOG/CTCAE 4.0 criteria. The data was analyzed and compared with published literature. Recommendations were achieved in -V10 -95%, V20-97% and V30-100%. All parameters were met in all patients with rectal and anal cancers. Out of 49 patients, 40% had grade 1, 22% had grade 2, 30% had grade 3 and 6% had grade 4 toxicity. Grade 3 and higher toxicities are summarized in the table. All patients completed chemotherapy except 8% missed and 12% needed dose reduction for the last cycle. A total of 14% patients needed hospitalization and 12% needed transfusion. Overall, severe myelotoxicity decreased from 60% to 33% for cervical cancer. Grade 2 or higher myelotoxicity decreased from 45% to 36% for rectal cancer. The toxicity rates for anal cancer are comparable at 55% to the previously reported rate of 51%. The rates of myelotoxicity have decreased with the utilization of the current dose constraints in IMRT planning for cervical and rectal cancer however neutropenia rates continue to be high for anal cancer, which may be attributed to the toxic effects of chemotherapy with mitomycin and 5-FU used concurrently. Further research is needed to validate the findings of this study in larger population in multi institutional setting.Poster Viewing Abstract 2366; TableGrade 3 or higher toxicityLeukopeniaNeutropeniaThrombocytopeniaAnemiaRectal cancer2/19 (10%)2/19 (10%)00Cervix cancer7/21 (33%)3/21 (14%)2/21 (9%)3/21 (14%)Anal cancer5/9 (55.5%5/9 (55.5%)00Total14/49 (28.5%)10/49 (20%)2/49 (4%)3/49 (6%) Open table in a new tab

Comparison of 2 Contouring Methods of Bone Marrow on CT and Correlation With Hematological Toxicities in Non–Bone Marrow–Sparing Pelvic Intensity-Modulated Radiotherapy With Concurrent Cisplatin for Cervical Cancer

To compare volumes and dose volume histogram (DVH) parameters for bone marrow contours using 2 methods on computed tomography (CT) and correlation with grade 2 or higher hematological toxicity (HT) in patients with cervical cancer treated with non-bone marrow-sparing intensity-modulated radiotherapy (IMRT) with concurrent cisplatin. The planning CT scans of 47 patients prospectively enrolled and treated with IMRT arm of a phase 2 trial (NCT00193804) contoured for pelvic bone marrow in 2 sets; whole bone (WB), and freehand (FH) inner cavity of bone. Various subvolumes were made in each set--sacrum, ilium, ischium, lower pelvis, lumbosacral spine, sacrum, and whole pelvis--and compared for volume and DVH parameters (V(10), V(20), V(30), and V(40)) using paired t test. The hematological parameters during RT compiled from electronic database analyzed for higher than grade 2 (Radiation Therapy Oncology Group) HT and correlated with DVH parameters using log regression analysis (P < 0.05 significant). The FH subvolumes were 25% to 30% of WB. The mean DVH parameters V(10), V(20), V(30), and V(40) for whole-pelvis FH and WB were 86.5%, 77.5%, 62.5%, and 40.5%; and 88%, 79.6%, 62.9%, and 40%, respectively. There was significant difference between the DVH parameters of 2 sets (P < 0.05) for all subvolumes except ischium V(20), sacrum V(10), and lumbosacral spine V(10). The leukopenia, neutropenia, anemia, and thrombocytopenia higher than grade 2 was seen in 53%, 29.8%, 65.9%, and 10.6%, respectively. The mean V(10) for whole pelvis was less than 90% for both sets. On both univariate and multivariate analyses, only FH whole pelvis V(40) more than or equal to 40% correlated with higher than grade 2 leukopenia (Mann-Whitney U test, P = 0.026) and neutropenia (P = 0.05) with odds ratio, 4 (95% confidence interval, 1.166-13.728; P = 0.028). The FH bone marrow cavity volume is a better surrogate of active bone marrow on CT images and correlated with higher than grade 2 HT (V(40) >40%). Further prospective studies validating significance of high-dose effects and identifying correlation of bioimaging with CT contouring are warranted.