Max Dose Research Articles

Monte Carlo simulation of 6-MV dynamic wave VMAT deliveries by Vero4DRT linear accelerator using EGSnrc moving sources.

The commissioning and benchmark of a Monte Carlo (MC) model of the 6‐MV Brainlab‐Mitsubishi Vero4DRT linear accelerator for the purpose of quality assurance of clinical dynamic wave arc (DWA) treatment plans is reported. Open‐source MC applications based on EGSnrc particle transport codes are used to simulate the medical linear accelerator head components. Complex radiotherapy irradiations can be simulated in a single MC run using a shared library format combined with BEAMnrc “source20.” Electron energy tuning is achieved by comparing measured vs simulated percentage depth doses (PDDs) for MLC‐defined field sizes in a water phantom. Electron spot size tuning is achieved by comparing measured and simulated inplane and crossplane beam profiles. DWA treatment plans generated from RayStation (RaySearch) treatment planning system (TPS) are simulated on voxelized (2.5 mm3) patient CT datasets. Planning target volume (PTV) and organs at risk (OAR) dose–volume histograms (DVHs) are compared to TPS‐calculated doses for clinically deliverable dynamic volumetric modulated arc therapy (VMAT) trajectories. MC simulations with an electron beam energy of 5.9 MeV and spot size FWHM of 1.9 mm had the closest agreement with measurement. DWA beam deliveries simulated on patient CT datasets results in DVH agreement with TPS‐calculated doses. PTV coverage agreed within 0.1% and OAR max doses (to 0.035 cc volume) agreed within 1 Gy. This MC model can be used as an independent dose calculation from the TPS and as a quality assurance tool for complex, dynamic radiotherapy treatment deliveries. Full patient CT treatment simulations are performed in a single Monte Carlo run in 23 min. Simulations are run in parallel using the Condor High‐Throughput Computing software1 on a cluster of eight servers. Each server has two physical processors (Intel Xeon CPU E5‐2650 0 @2.00 GHz), with 8 cores per CPU and two threads per core for 256 calculation nodes.

Dosimetric comparison of intensity-modulated radiation therapy (IMRT) and field-in-field (FIF) technique for head-and-neck cancer

AbstractPurpose:This study compared the plan dosimetry between the intensity-modulated radiation therapy (IMRT) and field-in-field (FIF) technique for head-and-neck cancer using the Elekta Monaco treatment planning system (TPS).Materials and methods:A total of 20 head-and-neck cancer patients were selected in this study. IMRT and FIF plans for the patients were created on the Monaco TPS (ver. 5.11.02) using the 6-MV photon beam generated by the Elekta Synergy linear accelerator. The dose–volume histograms, maximum doses, minimum doses, mean doses of the target volumes and organs-at-risk (OARs), conformity index (CI), homogeneity index (HI) and monitor units (MUs) were determined for each IMRT and FIF plan. All IMRT plans passed the patient-specific quality assurance tests from the 2D diode array measurements (MatriXX Evolution System, IBA Dosimetry, Germany).Results:The results showed that the dose distribution to the target volumes of IMRT plans was better than FIF plans, while the dose (mean or max dose) to the OAR was significantly lower than FIF plan, respectively. IMRT and FIF resulted in planning target volume coverage with mean dose of 71·32 ± 0·76 and 73·12 ± 0·62 Gy, respectively, and HI values of 0·08 ± 0·01 (IMRT) and 0·19 ± 0·06 (FIF). The CI for IMRT was 0·98 ± 0·01 and FIF was 0·97 ± 0·01. For the spinal cord tolerance (maximum dose < 45 Gy), IMRT resulted in 39·85 ± 2·04 Gy compared to 41·37 ± 2·42 Gy for FIF. In addition, the mean doses to the parotid grand were 27·27 ± 7·48 and 48·68 ± 1·62 Gy for the IMRT and FIF plans, respectively. Significantly more MUs were required in IMRT plans than FIF plans (on average, 846 ± 100 MU in IMRT and 467 ± 41 MU in FIF).Conclusions:It is concluded that the IMRT technique could provide a better plan dosimetry than the FIF technique for head-and-neck patients.

Impact of lung tumor motion on dose delivered to organ at risk in lung stereotactic body radiation therapy

To evaluate the amplitude of lung tumor motion and impact of tumor motion on dose delivered to the organs at risk (OARs) during lung stereotactic body radiation therapy (SBRT). This study included 55 patients (30 males and 25 females) with lung cancer who had a small gross tumor volume (GTV). SBRT lung cancer patients were treated with a prescribed dose of 60 Gy in 4 to 8 fractions. Radiotherapy plans were planned in Pinnacle 9.10 with two partial dynamic conformal arcs (DCAs) for the peripheral region (PR) and three to four partial DCAs for the central region (CR). The amplitude of tumor motion and their impact on the maximum dose delivered (Dmax) to the OARs were evaluated in the upper lobe (UL) and lower lobe (LL) in cases of CR and PR tumor’s localizations. The median tumor motions between CR and PR were 4.5 vs 2.2 mm in the UL and 12.5 vs 7.0 mm in the LL. Max dose delivered to the OARs between CR and PR in the UL and LL were as follows: 6.7 vs 8.9 Gy and 9.1 vs 11.7 Gy for the spinal cord; 15.2 vs 0.6 Gy and 22.4 vs 7.6 Gy for the heart; and 11.7 vs 10.8 Gy and 14.8 vs 9.8 Gy for the esophagus, respectively. The dose received by the OARs depends on the amplitude of tumor motion and is relative to the OAR’s location and motion, due to patient respiration and heart contribution.

Isavuconazonium Sulfate Use in Multi-Modal Management of Invasive Zygomycosis in Four Pediatric Allogeneic Hematopoietic Cell Transplant Patients

Prolonged neutropenia increases risk for lethal invasive fungal infection (IFI) such as Rhizopus. Isavuconazonium sulfate is a new triazole that lacks pediatric dosing recommendations. Clinical courses of 4 pediatric patients with IFI in the peri-allogeneic hematopoietic cell transplantation (alloHCT) period between 2015 and 2017 were reviewed, including previously unreported pharmacokinetic and safety data. IFI included Rhizopus and presumed fungal meningitis. Isavuconazonium sulfate was initiated with a loading dose followed by daily dosing, adjusted to a goal trough >3 ug/mL based on adult literature. This target was achieved at a median of 7 days, demonstrating varying rates of metabolism. Renal insufficiency, electrolyte disturbances, and transaminitis were noted, though attribution was confounded by other alloHCT complications. 1 patient survived infection-free to hospital discharge and 1 of 3 deceased patients had evidence of unresolved IFI (Case 2). Case 2 was subtherapeutic for 39% of the duration of treatment, compared to others at an average of 29%, suggesting this target trough to be clinically relevant. We recommend initiation of isavuconazonium sulfate at 10 mg/kg with a max dose of 372 mg. A loading dose of 10 mg/kg is utilized every 8 hours for 6 doses followed by 10 mg/kg dosing every 24 hours. Monitoring must continue beyond steady state. If early monitoring is not possible, we recommend a first drug level at week 3. If dose increases are required, a partial reload has been more successful instead of increasing daily doses. Further larger studies are needed to demonstrate optimum dosing in pediatric patients. Figure 1 Disclosures No relevant conflicts of interest to declare.

Dosimetric parameters associated with radiation-induced esophagitis in breast cancer patients undergoing regional nodal irradiation

Background/PurposeRates of acute esophagitis in breast cancer patients undergoing regional nodal irradiation (RNI) are under-reported. We set to identify esophageal dose–volume constraints associated with grade 2 esophagitis (G2E). We hypothesized that the G2E rate was higher with intensity modulated radiation therapy (IMRT) vs. 3D conformal radiation therapy (3DCRT). Materials/MethodsWe identified patients that received RNI (50 Gy/25 fractions) from 1/2013 to 6/2019. We retrospectively contoured the esophagus in a consistent manner and recorded esophageal mean dose, max dose, and V10–V50. Our primary endpoint was the G2E rate. Receiver operating characteristics curves analysis (e.g., Youden’s J statistic) were used to determine the cutpoints for the dosimetric parameters which were then tested in logistic regression models. ResultsWe identified 531 patients (50% left-sided; 41% IMRT; 16.2% G2E). G2E was significantly higher in IMRT vs. 3DCRT patients (23.6% vs. 10.9%, p < 0.0001). All esophageal dosimetric parameters were significantly associated with G2E after adjusting for age and laterality. The cutpoints for esophageal mean dose, V10 and V20 were 11 Gy, 30%, and 15%, respectively. The associations between the dichotomized dose–volume parameters and G2E were OR = 3.82 (95% CI 2.28–6.40, p < 0.0001) for esophageal mean dose, OR = 5.37 (95% CI 3.01–9.58, p < 0.0001) for esophageal V10, and OR = 3.23 (95% CI 1.93–5.41, p < 0.0001) for esophageal V20. ConclusionIn patients receiving RNI with modern techniques, we found that G2E occurs in >15%, and more frequently with IMRT. These data strongly support the routine contouring of the esophagus in RNI planning, and our constraints should be incorporated in future prospective protocols of RNI.

Impact of Multi-criteria Optimization on 6-MV Flattening Filter-Free Volumetric Modulated Arc Therapy for Craniospinal Irradiation

Introduction: Volumetric modulated arc therapy (VMAT) is an advanced technique used for radiotherapy treatment using different optimization modes. The present study aimed to evaluate Multi-criteria Optimization (MCO) influence on VMAT for Craniospinal Irradiation. Material and Methods: Fifteen CSI patients treated with 23.4 Gy/13 fractions followed by a boost dose of 6-MV flattening filter-free beams were chosen for this study. Conventional VMAT (c-VMAT) plans were generated for Elekta Versa HD™ linear accelerator. Keeping all other parameters constant, c-VMAT plans combined with MCO (MCO-VMAT) were created for comparison. We compared homogeneity index (HI), conformity index (CI), planning target volume (PTV) dose coverage (D98%), organ at risk (OAR) dose, normal tissue integral dose (NTID), volume receiving ≥ 5 Gy and ≥ 10 Gy by normal tissue, delivery time (DT), monitor units (MUs), and calculation time (CT). Results: Our findings demonstrated that HI and CI improved slightly in MCO-VMAT, in comparison with c-VMAT (P>0.05). No significant dose difference was observed in D98% for PTV and volume receiving the dose of ≥ 5 Gy, ≥ 10 Gy, and NTID (P>0.05). A slight increase was found in maximum dose to PTV in VMAT-MCO, compared to c-VMAT (P>0.05). The mean dose, max dose, and dose received by OAR were significantly lower in VMAT-MCO as compared to c-VMAT (p 0.05). Conclusion: The MCO-VMAT can be used for CSI, without compromising target coverage, reduced OAR dose by accepting a slight increase of MUs, delivery and calculation time as compare to c-VMAT.

Verification and Evaluation of Radiation Doses received by organs at risk in (3D-CRT) and IMRT technique for breast cancer

External beam radiotherapy can be delivered more precisely by using three Dimensional Conformal Radiotherapy (3D-CRT) technique, which is a traditional method used for whole breast radiotherapy. 3D-CRT includes standard wedged tangents (two opposed wedged tangential photon beams), which is based on three Dimensional images (3D) from a special computed tomography (CT scan). Overseas notification form advent of CT scans and more powerful computers have improved dose calculation algorithms and Multi-leaf Collimators (MLCs). Consequently, 3D-CRT is able to shape the Radiotherapy Beam (RTB) closely to match the target shape and volume. Intensity Modulated Radiation Therapy (IMRT) technique has the ability to improve sparing of normal tissues and treatment results of radiotherapy (RT). RT is a standard adjuvant therapy in conservative treatment of breast cancer (BC). The IMRT technique is used for many treatment sites, allowing for improved normal tissue sparing, more conformal dose distributions and prevention of secondary cancer. The purpose of this study is to verify and evaluate between the outcome of Radiation Treatment Plans (RTP) of left-sided whole breast irradiation of IMRT technique, and 3D-CRT technique to organs at risk (OAR) that are proximal to the target volume during breast radiotherapy. These include left lung, right lung, heart, and spinal cord by different numbers of beam in left sided breast at Zhianawa cancer center (ZCC) – Sulaimany-KR-Iraq. A second aim is to establish a guideline for breast cancer radiotherapy planning at ZCC. Thirteen patients with left-sided, breast carcinoma who had received radiotherapy were selected for this study. The dose prescriptions for the patients were different according to each patient’s cancer stage, using 6, 18 MV photons. The clinical target volume [CTV] was contoured as a target volume and the contralateral breast, left lung, right lung, heart, and spinal cord tissues as OAR. The two different planning techniques were analyzed for 13 patients with left-sided breast conserving surgery. Plans were compared on the basis of planning target volume (PTV) dose conformity index (CI), homogeneity index (HI) and the volumes of normal tissues treated based on dose-volume histograms (DVHs). DVHs were calculated for the PTV, heart, left lung, right lung, spinal cord and soft tissue surrounding the breast PTV (VOB) volume. IMRT techniques slightly improved homogeneity ( HI) than 3D (0.16.04 vs. 0.22, p<0.068). However, there was no significant difference between IMRT and 3D-CRT plans regarding CI. No significant difference was noted in CI by 3D and IMRT as both showed similarity, p< 0.190 ); IMRT technique benefited patients more than 3D-CRT by reducing the high-dose (40.05 Gy) volume for the heart. The heart’s mean dose was significantly lower in 3D compared to IMRT (3.58 Gy vs. 10.07Gy, respectively; p < 0.0001). Both the mean dose of the left lung and right lung, were significantly lower for 3D compared to IMRT (10.18Gy vs. 14.26Gy and 0.34 vs. 4.17 respectively; p < 0.001), and p< 0.0001. Cord Max. Cord Max dose was significantly lower in 3D compared to IMRT (6.83Gy % vs. 20.89 Gy%, p < 0.0001). IMRT plans improved by increasing low-dose volume (Lift lung, and Spinal cord soft tissue surrounding the breast) compared with 3D-CRT plans (P<0.0001) but with Right lung P<0.575. However, 3D-CRT plans were improved by increasing low-dose volume (heart) compared with IMRT plans (P<0.230)

68Ga-DOTATATE PET/MRI as an Adjunct Imaging Modality For Radiation Treatment Planning Of Meningiomas

Meningiomas express somatostatin receptor 2 (SSTR2). PET imaging with [68Ga]-DOTATATE, which targets SSTR2, has demonstrated clinical utility in delineating meningioma versus reactive dural thickening, particularly in the postoperative setting. Our study provides comparative volumetric and dosimetric analyses validating DOTATATE PET/MRI-assisted target delineation for radiotherapeutic planning of meningiomas. As a secondary aim, adverse events and 6-month progression-free survival rates are reported. We identified 9 residual / recurrent meningiomas in 8 patients who underwent 68Ga-DOTATATE PET/MRI prior to fractionated stereotactic radiosurgery (SRS) from 1/1-12/31/19. Demographic and clinical data were collected. CT simulation scans were fused with DOTATATE PET/MRI. Gross target volumes (GTV) were derived from the MRI and DOTATATE PET (acquired simultaneously). All GTV were given a 3.0 mm isometric expansion to generate the planning target volume (PTV). Patients received SRS to a nominal dose of 35 Gy in 5 fractions. Ascribing an α/β = 6 for atypical meningiomas produced a biologically equivalent dose (BED) of 75.83 Gy. Each patient was retrospectively recontoured per the RTOG 0539 intermediate-risk group cohort and received 54 Gy in 30 fractions (BED = 70.2 Gy). Planning volumes from DOTATATE PET/MRI-assisted and SOC plans were compared. All treatment related data were converted to EQD2 for dosimetric analysis. Mean and maximum equivalent doses were generated for target volumes, and OARs within 1 cm of the PTV, and compared using Wilcoxon matched pairs signed rank test. The cohort comprised 8 recurrent / residual WHO grade II meningiomas and 1 recurrent WHO grade I meningioma. BED max and mean were higher among DOTATATE-PET/MRI-guided plans (table). While PET/MRI-guided planning did not significantly reduce mean GTV, it significantly reduced mean PTV, and mean and max dose to the whole brain, optic nerves and scalp. While underpowered to reach significance, DOTATATE-guided plans reduced mean and max doses to the lens, eyes, chiasm, cochlea, brainstem, and hippocampi by at least 50%. Acute side effects were limited to focal alopecia in 1 patient. No recurrences were detected among 3 patients who underwent 6-month post-treatment imaging. [68Ga]-DOTATATE-PET/MRI improves post-operative target delineation for radiotherapy in patients with intracranial meningiomas, often resulting in PTV reduction and decreased OAR dose, compared with plans generated from SOC (MRI-based) planning. Our findings warrant larger studies evaluating DOTATATE-PET/MRI in the radiotherapeutic planning of meningiomas.Abstract 3552; TableParameterDOTATATE- unassisted planDOTATATE - planpGTV mean (cc)16.44.1>0.05PTV mean (cc)71.411.1<0.05BED mean (Gy)55.262.9<0.05BED max (Gy)62.674.9<0.05Whole brain mean dose (Gy)6.581.61<0.05Whole brain max dose (Gy)60.971.4<0.05Scalp max dose (Gy)54.318.8<0.05Optic nerve max (Gy)41.317.3<0.05 Open table in a new tab

Automatic VMAT Planning via MLC Dynamic Sequence Prediction (AVP-DSP): A Novel Deep-Learning Method for Real-Time Prostate Treatment Planning

VMAT treatment planning requires time-consuming DVH-based inverse optimization, which impedes its application in time-sensitive situations. This work aims to develop a deep-learning based algorithm, Automatic VMAT Planning via MLC Dynamic Sequence Prediction (AVP-DSP), for rapid prostate VMAT treatment planning. In general, AVP-DSP utilizes a series of 2D projections of a patient’s CT volume and contour structures to generate a single 360º dynamic MLC sequence in a VMAT plan. Specifically, AVP-DSP first generates 1) projections of PTV and organs-at-risk (OARs) contours at isocenter plane; 2) projections of CT attenuation coefficients at the PTV’s beam exit interface at 100 control point angles. These projections are used as inputs of a novel U-net design, which has a 4-resolution-step analysis path and a 4-resolution-step synthesis path. Each layer is composed of two 3×3×3 convolutions followed by an exponential linear unit (ELU) activation. The outputs are binarized MLC aperture shapes at 100 control points, which are subsequently resampled and sent to a commercial treatment planning system (TPS) using an automated scripting interface for plan finalization. AVP-DSP was developed based on 131 previous prostate patients who received simultaneously-integrated-boost (SIB) treatment (58.8Gy/70Gy to PTV58.8/PTV70 in 28fx). All patients were planned by a 360º single-arc VMAT technique using an in-house knowledge-based planning tool in a commercial TPS. 120 plans were used in AVP-DSP training/validation, and the selection of 100 control points were based on the study of dose rate distributions of the 120 plans. During U-net training, categorical cross-entropy was used as the loss function. 11 plans were used as independent tests. Key dosimetry metrics achieved by AVP-DSP were compared against the ones (KBP plans) planned by the commercial TPS. After dose normalization (PTV70 V70Gy = 95%), all 11 AVP-DSP test plans achieved clinically acceptable spatial dose distribution. Bladder (V70Gy = 5.8±2.4cc) and rectum (V70Gy = 2.7±1.9cc) high dose results in AVP-DSP plans were comparable with the KBP plan results (bladder V70Gy = 4.1±2.0cc, rectum V70Gy = 1.4±0.7cc). Femoral heads high dose results were also similar. In terms of low dose sparing, V40Gy results of bladder (19.3±9.6%) and rectum (27.9±5.9%) in AVP-DSP plans were close to KBP plan results (bladder 17.7±8.9%; rectum 24.0±5.0%) without clinical-relevant differences. However, 3D body max dose results in AVP-DSP plans (D1cc = 113.1±1.5%) were inferior to the KBP plans (D1cc = 106.7±0.8%). On average, AVP-DSP used 30 seconds for a plan generation in contrast to the current clinical practice (>20 minutes). Results showed that AVP-DSP can achieve clinically acceptable dosimetric quality in prostate VMAT treatment planning. With its high efficiency, AVP-DSP holds a great potential of real-time prostate VMAT planning application.

Patterns of Regional Failure in Patients with Pancreatic Cancer treated with Stereotactic Body Radiation Therapy

Stereotactic body radiation therapy (SBRT) is a treatment option for locally advanced pancreatic cancer. Current practice is to target the gross tumor volume (GTV) only and omit elective nodal irradiation, which may lead to increased regional failures. In this study, we review the patterns of regional failure of our patients treated with SBRT. We retrospectively reviewed all patients diagnosed with pancreatic cancer treated with SBRT to the GTV only from 2003 to 2019 in our institution with regional nodal failure on at least one follow-up scan. Major blood vessels (celiac artery (CA), superior mesenteric artery (SMA), portal vein (PV), and aorta) were contoured, and the distance of the nodal failures measured. Regional nodal failure was defined as new lymphadenopathy within 1.5 cm of CA, SMA, and PV, and within 2cm of aorta in accordance with RTOG consensus contouring guidelines. Follow-up scans were fused with the treatment planning scan, and doses to the regional failures were computed. They were then drawn to one template CT scan for mapping. Patients were excluded for regional mapping if they had incomplete SBRT plan data or follow-up scan images. Out of 355 patients diagnosed with pancreas cancer treated with SBRT in our institution, 23 patients (6.5%) had identified regional nodal failure in their follow-up. Thirteen (57%) patients had locally advanced disease treated definitively, 4 (17%) were neoadjuvant prior to Whipple, 3 (13%) were treated palliatively and were metastatic at presentation, and 3 (13%) were recurrence after Whipple or conventional radiotherapy. The median prescribed dose to the planning treatment volume (PTV) was 33 Gy (range, 24 – 40 Gy) in 5 (range, 1-5) fractions. The mean PTV dose delivered BED 10 is 66.63 Gy (range, 27.01-121.19Gy) There were 0 isolated regional failures; 17 (74%) regional failures occurred with simultaneous distant failure, 2 (9%) had distant recurrence before they had locoregional failure, 3 (13%) had simultaneous local progression, and 1 (4%) had local progression before regional failure. We identified 30 nodal failures from 23 patients. Nineteen (63%) nodal failures occurred within the para-aortic nodes, followed by 4 SMA nodal failures (17%), 5 CA failures (22%), and 2 PV failures (9%). The mean distance from CA, SMA, aorta, and PV were 0.72, 1.12, 0.80, and 0.58 cm respectively. The median mean, min, and max doses received by the regional nodes were 2.12 Gy (range, 0.07-20.77Gy), 0.87 Gy (range, 0-17.51Gy), and 4.02 Gy (range, 0.07-24.2 Gy) respectively. Regional failures with pancreatic SBRT were overall rare with a crude rate of 6.5%, none of which occurred in isolation as the first site of failure. The most common sites of regional failure were the para-aortic nodes followed by the CA nodes and then SMA nodes. Although this data supports the continued exclusion of elective nodal regions with pancreatic SBRT, the risk of nodal failures may increase with improvements in systemic therapy.

Dosimetric Investigation Of Radiotherapy-Related Trigeminal Nerve Toxicity In Oral Cavity And Oropharynx Cancer

Trigeminal nerve (TGN) damage due to radiotherapy (RT) is an expected complication in head and neck cancer because of its anatomic location. In this study, in oral cavity and oropharyngeal cancer patients we aimed to investigate the dosimetric relationship between RT and TGN toxicity, that was previously observed in our study in parotid tumor patients. Nineteen patients treated with adjuvant or definitive RT between 2013 and 2019 were retrospectively evaluated. TGN including ophthalmic, maxillary and mandibulary branches was contoured subsequently on RT planning tomography scans by using the contouring guideline for TGN and its branches in head and neck cancer published in 2018. The dose volume histogram over total dose was generated in order to determine the maximum dose (Dmax) for TGN, max dose for remaining TGN extracted from PTV (PTV-TGN Dmax), the dose for specified volumes such as 0.1 cm3 (D0.1), 0.2 cm3 (D0.2) ), 0.5 cm3 (D0.5), 1 cm3 (D1) and 2 cm3 (D2) volumes and then the reflection of these doses on toxicity. TGN late toxicity was graded according to CTCAE v5.0. The median age was 64 years (range 24-85 years) and the mean follow-up was 50 months (range 35-65 months). Of the 19 patients, 13 patients (68%) developed grad I-III TGN toxicity distributed as grade I in 9 patients, grade II in 3 patients and grade III in 1 patient. The median duration of toxicity was 16 months after RT. TGN damage manifested itself as difficulty in jaw movements in 4 (30%), loss of sensation in 1 (8%), paresthesia in 5 (38%) and pain in 3 (23%) patients. The characteristics of patients are summarized in Table 1. The only clinical factor related with TGN toxicity was found to be the type of treatment (definitive CRT vs adjuvant CRT vs adjuvant RT (p = 0.034). The dosimetric parameters related with toxicity were total RT dose (p = 0.004), TGN Dmax (p = 0.002), PTV-TGN Dmax (p = 0.028), D2 (p = 0.001), D1 (p = 0.007), D0.5 (with p = 0.005), D0.2 (p = 0.001), and D0.1 (p = 0.001) doses respectively. In terms of TGN toxicity, threshold values for TGN Dmax, PTV-TGN Dmax, D0.1, D0.2, D0.5, D1 and D2 were detected to be as 67.5 Gy, 66.7 Gy, 64.9 Gy, 64 Gy, 63 Gy and 59.3 Gy, respectively. TGN late toxicity is an important complication of RT that has not been yet clearly defined in head and neck cancer. During RT planning, taking into account of cut off values which has correlated with our previous study may play a remarkable role.Abstract 3965; TableParametern (%)Gender Female Male8(42) 11(58)Tumor location5(26)Tongue2(11)Lower Lip2(11)Retromolar Trigon2(11)Hard Palate2(11)Buccal Mucosa1(5)Gingiva1(5)Base of mouth3(15)Tonsil1(5)Oropharynx undefinedStage I II III IVA IVB3(16) 3(16) 4(21) 8(42) 1(5)Histology SCC Mucoepithelial Carcinoma Adenoid Cystic Carcinoma16(84) 2(11) 1(5)LVI Positive Negative Unknown1(5) 14(74) 4(21)PNI Positive Negative Unknown5(26) 11(58) 3(16)Surgery margin Positive Close Negative13(68) 8(42) 1(5) 4(21)Treatment Procedure Definitive CRT Surgery + RT Surgery + CRT6(32) 5(26) 8(41) Open table in a new tab

Phase I Trial of an IMRT-based Contralateral Esophagus Sparing Technique (CEST) in Locally Advanced NSCLC and SCLC Treated to 70 Gy

Severe acute esophagitis (AE), grade (G) ≥3 by CTCAE, occurs in ∼7-21% of locally advanced NSCLC or SCLC patients (pts) treated with concurrent chemo/radiation therapy (CRT) to ≥60 Gy once-daily. G3+ AE represents a dose-limiting toxicity and is associated with poor treatment outcomes, as shown in RTOG 0617. We hypothesized that formalized sparing of the contralateral esophagus (CE) reduces the risk of severe AE by preserving partial organ functionality. We performed a phase I clinical trial to prospectively test an empirically developed CE-sparing technique on an IRB-approved protocol (registered with clinicaltrials.gov). Pts with locally advanced NSCLC (+/- solitary brain metastasis) or limited-stage SCLC with gross tumor within 1 cm of the esophagus were eligible. Pts were treated with IMRT or VMAT and daily CBCT to 70 Gy at 2 Gy/fraction. The PTV was a uniform 5 mm expansion. The esophageal wall contralateral to gross tumor was contoured as an avoidance structure to guide a steep dose falloff gradient across the esophagus, except on slices where tumor surrounded the esophagus. Target coverage was always prioritized over CE sparing, and 99% of ITV and PTV were covered by 70 Gy and ≥63 Gy, respectively. To be analyzable for the primary endpoint of G3+ AE (CTCAE v4), pts needed to have received concurrently ≥5 cycles of weekly carboplatin/paclitaxel or ≥2 cycles of platinum + pemetrexed or etoposide and have had ≤3 days of unplanned treatment interruption unrelated to esophagitis. Survival times were calculated from date of registration. Of 27 pts accrued between 7/2015 and 1/2019, 25 completed treatment and were analyzable for secondary endpoints while 20 were analyzable for the primary endpoint (analysis was performed with complete follow-up until February 9, 2020). Median age was 67 years (range, 51-81 years). There were 15 males and 10 females. Nineteen pts had NSCLC and 6 had SCLC. AJCC stage (7th ed.) distribution was: IIIA 52%, IIIB 40%, IV 8%. Total dose was 70 Gy (n = 24) or 68 Gy (n = 1). Median esophagus V60 was 11% (1-29%). Median CE max dose, V55, and V45 were 66 Gy (44-71 Gy), 1.4cc (0-5.3cc), and 2.7cc (0-9.2cc), respectively. Median follow-up was 33.3 months (11.1-52.2 months). The rate of G3+ AE was 0%. Other radiation-related toxicities were: G2 AE 25%, G2+ pneumonitis 12% (G2 n = 2, G5 n = 1), G3+ cardiac toxicity 8% (G3 n = 1, G5 n = 1). There was no isolated local tumor failure. Two-year overall survival rate was 67% (95% CL, 45-82%), and median progression free-survival time was 25.9 months (95% CL, 11.2 to not reached). CE sparing is associated with substantially reduced AE in CRT pts treated to 70 Gy, with no G3+ AE despite gross tumor within 1 cm of the esophagus. We hypothesize that contralateral wall sparing converts the esophagus from a serial to a parallel organ, a concept that may be readily adaptable into clinical practice.

Prophylactic Gabapentin Results in Dramatic Reduction of Narcotic Utilization in Head and Neck Cancer Patients Undergoing Radiotherapy

A significant number of patients treated for head and neck cancer (HNC) develop pain from treatment requiring narcotic utilization. Pain mechanisms in HNC include both nociceptive and neuropathic components. Gabapentin (GP) was initially developed as an antiepileptic drug, but has proved as an effective treatment for neuropathic pain, increasingly in the oncologic setting. There have been several recent investigations into the use of GP in the multimodal management of HNC. While these early studies are promising, none has compared GP utilization during week 1 of radiotherapy (RT) or chemoradiotherapy (CRT) to a control group to evaluate impact on opioid requirement. Here we report a comparison of our opioid utilization comparing our GP cohort to a historical cohort treated prior to the routine utilization of GP. An institutional review board approved retrospective review of HNC patients treated December 2015-March 2019 with RT or CRT and prophylactic GP with a starting tapered regimen of 100mg-300mg three times daily (tid) during week 1 of therapy, with a max dose of 1200mg tid, escalated throughout treatment. This was compared to a control group of similarly matched historical cohort of 49 patients treated prior to GP being implemented. GP use, opioid use in morphine equivalent, pain score, mucositis, pharyngitis and dermatitis were recorded at each weekly on treatment visit and through-out follow-up evaluations. 139 patients from the GP arm and 49 patients from the historically matched control group were retrospectively analyzed after IMRT. Cohorts were well matched overall. Median gabapentin dose was 900mg tid. The absolute number of patients requiring any opioid pain medication was reduced by 50% in the GP cohort (77.6% vs. 38.9%), while still maintaining pain scores similar to those of patients historically treated with narcotics. Median difference in narcotic dose represented in morphine equivalents was significantly lower in the GP group at week 2 (p = .01) and remained significantly different until the last follow-up. On average, there was a 71.8% drop in nominal narcotic dose in the GP group compared to historical control. Adverse effects of gabapentin were minimal and reversed with stopping the medication. Reported fatigue scores were similar between groups. Overall PEG placement rate during radiation was 11.5% (15/130) as 9 patients had PEG tubes prior to starting radiation. Prophylactic GP can be can effectively and safely be administered to HNC patients undergoing RT or CRT and results in significant decrement in opioid requirement during treatment while achieving similar pain score improvement as narcotics. In the context of a global opioid crisis, these data would support GP as a widespread clinical standard in this patient population upon prospective validation of these findings.

Evaluating Maximum MU per Spot Thresholds on CNS Pencil Beam Proton Therapy Plan Quality

There are concerning reports of CNS toxicity in patients treated with proton therapy at doses lower than would be expected based on photon data estimates. Given the desire to mitigate risk of serious unexpected events, we propose limiting the maximum monitor unit weighting per spot (maxMU/spot) to the entire plan with the hypothesis that heavily weighted spots may pose an unforeseen risk of toxicity despite meeting objective dose constraints. This dosimetric study assesses the impact of maxMU/spot restrictions on pencil beam proton therapy (PBPT) plan quality. We hypothesize that plan quality may be preserved while still restricting the maxMU/spot, but there may be a threshold below which restrictions negatively impact plan quality. PBPT plans of 11 patients (9 consecutive, 2 additional with notably challenging plan objectives) were included, of which 3 plans included boosts, for a total of 14 nominal PBPT cases. Per nominal plan, a single dosimetrist created 4 test plans as outlined in Table 1, iteratively reducing the maxMU/spot in the plan. Test Plan 1, unrestricted in maxMU/spot, was the reference for all analyses (comparison sets 2 vs. 1; 3 vs. 1; and 4 vs. 1). The differences in each plan quality metric in each comparison set were analyzed using the Wilcoxon signed rank test, with p<0.05 significance testing. Beam-specific metrics in each comparison set were analyzed, defined by the root mean square deviation in beam metrics from the unrestricted plan. Linear regression with log transformation was performed to analyze the impact of restriction conditions on changes in the beam-specific max dose, heterogeneity, and % of target receiving the Rx/#beams. A total of 14 PBPT plans, 7 (50%) SFO, 7 (50%) MFO, 9 (64%) delivering >3500 cGy, 9 (64%) with 3 beams, 5 (36%) with 4-5 beams, and 7 (50%) without a range shifter were included. With increasing MU restriction, there were no differences in plan quality metrics of target coverage (V95% and V100%Rx), conformality and gradient indices, hot spot volume (V105%Rx), and dose to unaffected brain (V10%/30%/50%/70%/90%/100%Rx) across all comparison sets (p>0.05). However, there was a mean increase of 854 (2 vs. 1, p = 0.02), 869 (3 vs. 1, p = 0.025), and 892 (4 vs. 1, p = 0.007) total spots in the more restricted MU plans. MaxMU restriction did not significantly impact the beam-specific max dose (p = 0.259), heterogeneity (p = 0.305), and % of target receiving the Rx/#beams (p = 0.409). MaxMU/spot restriction did not negatively impact overall plan quality and beam-specific metrics within the thresholds evaluated in this study. Future studies should evaluate spot weighting with LET/RBE to determine if spot weighting manipulation may truly impact clinical outcomes and mitigate toxicity.Tabled 1Abstract 2601; Table; Iterative reduction maximum allowable MU per spot*PlanNo Range shifter (RS)2cm RS3cm RS5cm RS1No limitNo limitNo limitNo limit230405070320304060410203050∗1 MU = 1 cGY/mm2 at a 2 cm for monoenergetic proton beam Open table in a new tab

Technical Note: Patient dose from kilovoltage radiographs during motion-synchronized treatments on Radixact®.

PurposeSynchrony is a motion management system available on the Radixact linear accelerator that utilizes kilovoltage (kV) radiographs to track target motion and synchronize the delivery of radiation with the motion. Proper management of this imaging dose requires accurate quantification. The purpose of this work was to use Monte Carlo (MC) simulations to quantify organ‐specific patient doses from these images for various patient anatomies.MethodsPoint doses in water were measured per TG‐61 for three beam qualities commonly used on the Radixact. The point doses were used to benchmark a model of the imaging system built using the Monte Carlo N‐Particle (MCNP) transport code. Patient computed tomography (CT) datasets were obtained for 5 patients and 100 planar images were simulated for each patient. Patient dose was calculated using energy deposition mesh tallies.ResultsThe MCNP model was able to accurately reproduce the measured point doses, with a median dose difference of less than 1%. The median dose (D50%) to soft tissue from 100 radiographs among the 5 patient cases ranged from 2.0 to 4.6 mGy. The max dose (D1%) to soft tissue ranged from 6.2 to 31.0 mGy and the max dose to bony structures ranged from 20.2 to 71.7 mGy. These doses can be scaled to estimate total patient dose throughout many fractions.ConclusionsPatient dose is largely dependent on imaging protocol, patient size, and treatment parameters such as fractionation and gantry period. Organ doses from 100 radiographs (an approximate number for one fraction) on the Radixact are slightly less than the doses from Tomo MVCT setup images. Careful selection of clinical protocols and planning parameters can be used to minimize risk from these images.

Endoscopic and clinical correlation with dose to sigmoid colon in carcinoma cervix patients treated with radical radiotherapy.

Sigmoid colon, due to its close proximity to central tandem in intracavitary brachytherapy (BT), is at risk of receiving high dose, the clinical significance of which is not documented. This study was designed to assess the dose received by sigmoid colon following radical treatment and to correlate clinically with the sigmoid mucosal changes seen on sigmoidoscopy. This is a prospective study. Thirty histologically proven carcinoma cervix patients treated with radical radiotherapy were accrued. A baseline sigmoidoscopy was done and repeated at 6 months following completion of BT. The dose-volume parameters (DVP) were used to calculate the dose received by the sigmoid colon and correlate with symptoms along with the sigmoid mucosal changes. The following were the statistical methods used: frequency; percentages; and descriptive statistics such as mean ± standard deviation, Chi-square test, Kolmogorov-Smirnov test, and independent sample t-test. P < 0.05 was considered statistically significant. The dose of the sigmoid colon in patients with a sigmoidoscopy score of ≥2 was significantly high compared to that of patients with a score of <2 for DVP such as D0.1cc, D1cc, D2cc, D5cc, and mean dose, whereas max dose was not significantly high. The dose received by the sigmoid colon is directly proportional to the mucosal changes and hence possibly a higher morbidity. Tighter dose-volume constraints, better optimization techniques, and close follow-up sigmoidoscopy will help in the prevention and early treatment of long-term morbidity.

First report on the feasibility of a permanently implantable uni-directional planar low dose rate brachytherapy sheet for patients with resectable or borderline resectable pancreatic cancer

BackgroundMargin negative resection in pancreatic cancer remains the only curative option but is challenging, especially with the retroperitoneal margin. Intraoperative radiation therapy (IORT) can improve rates of local control but requires specially designed facilities and equipment. This retrospective review describes initial results of a novel implantable mesh of uni-directional low dose rate (LDR) Pd-103 sources (sheet) used to deliver a focal margin-directed high-dose boost in patients with concern for close or positive margins. MethodsEleven consecutive patients from a single institution with resectable or borderline resectable pancreatic cancer with concern for positive margins were selected for sheet placement and retrospectively reviewed. Procedural outcomes, including the time to implant the device and complications, and clinical outcomes, including survival and patterns of failure, are reported. A dosimetric comparison of the LDR sheet with hypothetical stereotactic body radiotherapy (SBRT) boost is reported. ResultsOne patient had a resectable disease, and 10 patients had a borderline resectable disease and underwent neoadjuvant treatment. Sheet placement added 15 min to procedural time with no procedural or sheet-related complications. At a median follow up of 13 months, 64% (n = 7) of patients are alive and 55% (n = 6) are disease-free. Compared to a hypothetical SBRT boost, the LDR sheet delivered a negligible dose to kidneys, liver, and spinal cord with a 50% reduction in max dose to the small bowel. ConclusionThis is the first report of the use of an implantable uni-directional LDR brachytherapy sheet in patients with resected pancreatic cancer with concern for margin clearance, with no associated toxicity and favorable clinical outcomes.

The Effect of Radiation Dose to the Pharyngeal Constrictor Musculature on Weight Loss During Treatment and Feeding Tube Dependence in Head and Neck Cancer

Radiation-associated dysphagia (RAD) is a common toxicity of radiotherapy (RT) for head and neck cancer, reported by nearly 50 percent of patients. Severe dysphagia can lead to feeding tube dependence, which significantly impacts quality of life. Studies have suggested that reduced radiation dose to the pharyngeal constrictor musculature (PCM) using intensity-modulated RT (IMRT) is associated with improved swallowing outcomes by a variety of measures. We aimed to identify dose-volume parameters of radiation to the PCM that are associated with weight loss during RT and percutaneous endoscopic gastrostomy (PEG) dependence as clinical measures of severe RAD. From a single institutional database, 115 patients with newly diagnosed head and neck squamous cell carcinoma of the oral cavity, nasopharynx, oropharynx, hypopharynx and larynx who underwent definitive or postoperative IMRT between January 1, 2014 and December 31, 2017 were identified after exclusion of patients with T1-2 stage larynx cancer, less than 6 months of follow-up and locoregional recurrence at any time. PCM was contoured prospectively and mean dose < 60 Gy was used as the dose constraint when possible. PCM dose-volume parameters were retrospectively collected from IMRT plans and logistic regression was used to analyze these data relative to percent weight loss during RT and duration of PEG use. 57% of patients had surgery prior to RT, 63% received concurrent chemotherapy and 70% had planned RT to the bilateral neck. 57% had some degree of dysphagia prior to RT. PEG tubes were placed prior to, during or just after RT in 45% of patients. The mean and median time from RT to PEG removal were 8.9 and 6.5 months respectively (range 1.9 to 36.7 months). The median percent weight loss during RT was 9.3% (range -5.7 to 23%). Definitive RT, bilateral neck volumes and concurrent chemotherapy were associated with weight loss and prolonged PEG use on univariate analysis. On multivariate analysis, female gender and concurrent chemotherapy were independently associated with prolonged PEG use and age < 60 and normal swallowing prior to RT were independently associated with weight loss > 10%. When adjusting for these significant confounding factors, PCM mean dose, max dose and V50-60 were significantly associated with prolonged PEG use: Means of these individual parameters for PEG use > 6 months were 57 Gy, 72 Gy, 80% and 54% respectively versus 48 Gy, 65 Gy, 58% and 28% for PEG use < 6 months. PCM V40 was significantly associated with > 10% weight loss during RT, with mean V40 of 85% for weight loss > 10% and 70% for weight loss < 10%. In this institutional cohort, IMRT dose to the total PCM correlated with severe RAD. Aiming to keep an overall PCM mean dose < 48 Gy and max dose < 65 Gy during IMRT planning may help reduce prolonged PEG dependence, while a PCM V40 < 70% may be associated with reduced treatment related weight loss.

Left anterior descending artery avoidance in patients receiving breast irradiation

PurposeDose to the left anterior descending artery (LAD) may be significant in patients receiving left-sided irradiation for breast cancer. We investigated if prospective contouring and avoidance of the LAD during treatment planning were associated with lower LAD dose. Methods and MaterialsWe reviewed dosimetric plans for 323 patients who received left whole breast or chest wall irradiation with or without internal mammary node (IMLN) coverage between 1/2014 and 1/2019 at a single institution. The LAD was contoured prospectively for 155 cases, and techniques were utilized to minimize LAD dose. Dose-volume-histograms from these patients were compared to those of 168 patients for whom the LAD was contoured retrospectively after treatment completion. EQD2 was calculated to account for fractionation differences. ResultsCompared to cases where the LAD was contoured retrospectively (n = 126), prospective LAD contouring (n = 124) was associated with lower unadjusted median max and mean LAD doses for 250 patients receiving whole-breast irradiation (WBI) without IMLN coverage: 8.5 Gy vs 5.2 Gy (p < 0.0001) and 3.6 Gy vs 2.7 Gy (p < 0.0001), respectively. EQD2 median max and mean LAD doses were also lower with prospective LAD contouring: 5.2 Gy vs 3.0 Gy (p < 0.0001) and 1.9 Gy vs 1.5 Gy (p < 0.0001), respectively. Compared to cases where the LAD was contoured retrospectively (n = 42), prospective LAD contouring (n = 31) was associated with lower max LAD doses for 73 patients with IMLN coverage: 20.4 Gy vs 14.3 Gy (p = 0.042). There was a nonsignificant reduction in median mean LAD dose: 6.2 Gy vs 6.1 Gy (p = 0.33). LAD doses were reduced while maintaining IMLN coverage (mean V90%Rx >90%). ConclusionsProspective contouring and avoidance of the LAD were associated with lower max and mean LAD doses in patients receiving WBI and with lower max LAD doses in patients receiving IMLN treatment. Further reduction in LAD dose may require stricter optimization weighting or compromise in IMLN coverage.

XeUS: A second-generation automated open-source batch-mode clinical-scale hyperpolarizer

We present a second-generation open-source automated batch-mode 129Xe hyperpolarizer (XeUS GEN-2), designed for clinical-scale hyperpolarized (HP) 129Xe production via spin-exchange optical pumping (SEOP) in the regimes of high Xe density (0.66–2.5 atm partial pressure) and resonant photon flux (~170 W, Δλ = 0.154 nm FWHM), without the need for cryo-collection typically employed by continuous-flow hyperpolarizers. An Arduino micro-controller was used for hyperpolarizer operation. Processing open-source software was employed to program a custom graphical user interface (GUI), capable of remote automation. The Arduino Integrated Development Environment (IDE) was used to design a variety of customized automation sequences such as temperature ramping, NMR signal acquisition, and SEOP cell refilling for increased reliability. A polycarbonate 3D-printed oven equipped with a thermo-electric cooler/heater provides thermal stability for SEOP for both binary (Xe/N2) and ternary (4He-containing) SEOP cell gas mixtures. Quantitative studies of the 129Xe hyperpolarization process demonstrate that near-unity polarization can be achieved in a 0.5 L SEOP cell. For example, %PXe of 93.2 ± 2.9% is achieved at 0.66 atm Xe pressure with polarization build-up rate constant γSEOP = 0.040 ± 0.005 min−1, giving a max dose equivalent ≈ 0.11 L/h 100% hyperpolarized, 100% enriched 129Xe; %PXe of 72.6 ± 1.4% is achieved at 1.75 atm Xe pressure with γSEOP of 0.041 ± 0.001 min−1, yielding a corresponding max dose equivalent of 0.27 L/h. Quality assurance studies on this device have demonstrated the potential to refill SEOP cells hundreds of times without significant losses in performance, with average %PXe = 71.7%, (standard deviation σP = 1.52%) and mean polarization lifetime T1 = 90.5 min, (standard deviation σT = 10.3 min) over the first ~200 gas mixture refills, with sufficient performance maintained across a further ~700 refills. These findings highlight numerous technological developments and have significant translational relevance for efficient production of gaseous HP 129Xe contrast agents for use in clinical imaging and bio-sensing techniques.