Sum Of Doses Research Articles

An energy-conserving dose summation method for dose accumulation in radiotherapy.

Radiation therapy often requires the accumulation of doses from multiple treatment fractions or courses for plan evaluation and treatment response assessment. However, due to underlying mass changes, the accumulated dose may not accurately reflect the total deposited energy, leading to potential inaccuracies in characterizing the treatment input. This study introduces an energy-conserving dose summation method to calculate the total dose in scenarios where patients experience changes in body mass during treatment. The proposed method transfers dose and mass data from dosimetry images, where the delivered doses were calculated, to a reference image using an energy and mass-conserving dose reconstruction technique. The reconstructed dose assumes the same resolution and dimension as the reference image. The transferred masses are averaged at each image voxel in the reference image to generate an average mass. The transferred doses are then adjusted by multiplying by the ratio of their transferred mass to the average mass, and subsequently summed to calculate a mass-weighted (MW) total dose at each voxel. This method is demonstrated with a case of lung cancer retreatment. The MW total dose was shown to be equivalent to the total deposited energy divided by the average mass. In the lung cancer retreatment case, the energy derived from the MW total dose was consistent with the sum of energy transferred from two treatments across all evaluated organs. The MW dose summation method can produce a total dose that accurately reflects the total energy deposited in each organ. The consistency may provide a robust foundation for verifying dose accumulations in adaptive radiotherapy.

Evaluation of cumulative dose distributions from external beam radiation therapy using CT-to-CBCT deformable image registration (DIR) for cervical cancer patients.

To investigate dose differences between the planning CT (pCT) and dose calculated on pre-treatment verification CBCTs using DIR and dose summation for cervical cancer patients. Cervical cancer patients treated at our institution with 45Gy EBRT undergo a pCT and 5 CBCTs, once every five fractions of treatment. A free-form intensity-based DIR in MIM was performed between the pCT and each CBCT using the "Merged CBCT" feature to generate an extended FOV-CBCT (mCBCT). DIR-generated bladder and rectum contours were adjusted by a physician, and dice similarity coefficients (DSC) were calculated. After deformation, the investigated doses were (1) recalculated in Eclipse using original plan parameters (ecD), and (2) deformed from planning dose (pD) using the deformation matrix in MIM (mdD). Dose summation was performed to the first week's mCBCT. Dose distributions were compared for the bladder, rectum, and PTV in terms of percent dose difference, dose volume histograms (DVHs), and gamma analysis between the calculated doses. For the 20 patients, the mean DSC was 0.68±0.17 for bladder and 0.79±0.09 for rectum. Most patients were within 5% of pD for D2cc (19/20), Dmax (17/20), and Dmean (16/20). All patients demonstrated a percent difference>5% for bladder V45 due to variations in bladder volume from the pCT. D90 showed fewer differences with 19/20 patients within 2% of pD. Gamma rates between pD and ecD averaged 94% for bladder and 94% for rectum, while pD and mdD exhibited slightly better performance for bladder (93%) and lower for rectum (85%). Using DIR with weekly CBCT images, the MIM deformed dose (mdD) was found to be in close agreement with the Eclipse calculated dose (ecD). The proposed workflow should be used on a case-by-case basis when the weekly CBCT shows marked difference in organs-at-risk from the planning CT.

417 Spatial correlation of EBRT and Interstitial Brachy with DIR based dose summation in oral cancers

417 Spatial correlation of EBRT and Interstitial Brachy with DIR based dose summation in oral cancers

Robustness of intensity modulated proton treatment of esophageal cancer for anatomical changes and breathing motion

Background and purposeIn this study, we assessed the robustness of intensity modulated proton therapy (IMPT) in esophageal cancer for anatomical variations during treatment. MethodsThe first sixty esophageal cancer patients, treated clinically with chemoradiotherapy were included. The treatment planning strategy was based on an internal target volume (ITV) approach, where the ITV was created from the clinical target volumes (CTVs) delineated on all phases of a 4DCT. For optimization, a 3 mm isotropic margin was added to the ITV, combined with robust optimization using 5 mm setup and 3 % range uncertainty. Each patient received weekly repeat CTs (reCTs). Robust plan re-evaluation on all reCTs, and a robust dose summation was performed. To assess the factors influencing ITV coverage, a multivariate linear regression analysis was performed. Additionally, clinical adaptations were evaluated. ResultsThe target coverage was adequate (ITV V94%>98 % on the robust voxel-wise minimum dose) on most reCTs (91 %), and on the summed dose in 92 % of patients. Significant predictors for ITV coverage in the multivariate analysis were diaphragm baseline shift and water equivalent depth (WED) of the ITV in the beam direction. Underdosage of the ITV mainly occurred in week 1 and 4, leading to treatment adaptation of eight patients, all on the first reCT. ConclusionOur IMPT treatment of esophageal cancer is robust for anatomical variations. Adaptation appears to be most effective in the first week of treatment. Diaphragm baseline shifts and WED are predictive factors for ITV underdosage, and should be incorporated in an adaptation protocol.

Adaptive radiotherapy for head and neck cancer: Pitfalls and possibilities from the radiation oncologist's point of view.

Patients with head and neck cancer (HNC) may experience substantial anatomical changes during the course of radiotherapy treatment. The implementation of adaptive radiotherapy (ART) proves effective in managing the consequent impact on the planned dose distribution. This narrative literature review comprehensively discusses the diverse strategies of ART in HNC and the documented dosimetric and clinical advantages associated with these approaches, while also addressing the current challenges for integration of ART into clinical practice. Although based on mainly non-randomized and retrospective trials, there is accumulating evidence that ART has the potential to reduce toxicity and improve quality of life and tumor control in HNC patients treated with RT. However, several questions remain regarding accurate patient selection, the ideal frequency and timing of replanning, and the appropriate way for image registration and dose calculation. Well-designed randomized prospective trials, with a predetermined protocol for both image registration and dose summation, are urgently needed to further investigate the dosimetric and clinical benefits of ART.

Multi-centre evaluation of variation in cumulative dose assessment in reirradiation scenarios

Background and PurposeSafe reirradiation relies on assessment of cumulative doses to organs at risk (OARs) across multiple treatments. Different clinical pathways can result in inconsistent estimates. Here, we quantified the consistency of cumulative dose to OARs across multi-centre clinical pathways. Material and MethodsWe provided DICOM planning CT, structures and doses for two reirradiation cases: head & neck (HN) and lung. Participants followed their standard pathway to assess the cumulative physical and EQD2 doses (with provided α/β values), and submitted DVH metrics and a description of their pathways. Participants could also submit physical dose distributions from Course 1 mapped onto the CT of Course 2 using their best available tools. To assess isolated impact of image registrations, a single observer accumulated each submitted spatially mapped physical dose for every participating centre. ResultsCumulative dose assessment was performed by 24 participants. Pathways included rigid (n = 15), or deformable (n = 5) image registration-based 3D dose summation, visual inspection of isodose line contours (n = 1), or summation of dose metrics extracted from each course (n = 3). Largest variations were observed in near-maximum cumulative doses (25.4 – 41.8 Gy for HN, 2.4 – 33.8 Gy for lung OARs), with lower variations in volume/dose metrics to large organs. A standardised process involving spatial mapping of the first course dose to the second course CT followed by summation improved consistency for most near-maximum dose metrics in both cases. ConclusionLarge variations highlight the uncertainty in reporting cumulative doses in reirradiation scenarios, with implications for outcome analysis and understanding of published doses. Using a standardised workflow potentially including spatially mapped doses improves consistency in determination of accumulated dose in reirradiation scenarios.

The Dosimetric Analysis of Duodenal and Intestinal Toxicity After a Curative Dose Re-irradiation Using the Intensity-Modulated Radiotherapy for Abdominopelvic Lymph Node Lesions.

This study aimed to examine the influence of dosimetric factors on gastrointestinal toxicity after radical re-irradiation for lymph node recurrence in the abdominopelvic region using a composite plan. Between January 2008 and March 2017, 33 patients underwent radical re-irradiation for lymph node recurrence in the abdominopelvic region with a complete overlap with previous radiation therapy (RT) with the median prescription dose of the second RTof 71.7 Gy10.Re-irradiation planning protocol for target volume and organs at risk (OARs) (duodenum, small and large intestines) was decided as follows: more than equal to 97% of the prescription dose was administered to the D95 (percentage of the minimum dose that covered 95% of the target volume) of planning target volume (PTV); minimal dose to the maximally irradiated doses delivered to 1cc [D1 cc] and 5cc [D5 cc] of OARs was set below 70 Gy3 and 50 Gy3, respectively; and D1 cc and D5 cc in the cumulative plans to OARs were 120 Gy3 and 100 Gy3.Kaplan-Meier analyses were performed to evaluate overall survival (OS) and univariate log-rank and multivariate Cox proportional hazards model analyses were performed to explore predictive factors. Using dose summation of the first and re-irradiation plans, we conducted a dosimetric analysis for grade ≥ 3 toxicities of the duodenum and intestine. With a median follow-up of 18 months, the two-year OSrate was 45.5%. The number of RT fields (localized or multiple) was a significant predisposing factor for OS rate with a hazard ratio of 0.23 (95% confidence interval 0.07-0.73). The two-year OS of the patients with a localized RT field was 63.6% and 9.1% for multiple RT fields (p= 0.00007). Four patients experienced grade ≥3 gastrointestinal toxicity related to re-irradiation (4/33=12.1%). We could not find any predisposing dosimetric value in the comparisons with and without toxicity. The dose constraints presented in this study are relatively low rates of toxicity, which may be useful when planning re-irradiation. Especially, for the patients who could be treated with localized RT field, radical re-irradiation with a high curative dose is a good option. No dosimetric predisposing factor was found for radical re-irradiation of abdominopelvic lesions in the composite plan.

Cumulative noise metric design considerations for the NASA Quesst community test campaign with the X-59 aircraft

The National Aeronautics and Space Administration (NASA) plans to collect X-59 aircraft dose-response data to inform international regulators in their efforts to establish acceptable noise standards to replace the current ban on overland supersonic commercial flight. For this upcoming community test campaign, the sound level from a supersonic overflight of the X-59 constitutes a single-event dose, and an end-of-day survey after multiple flight events constitutes a cumulative response. This study considers how X-59 community tests could be designed to explore the relationship between multiple single events and cumulative annoyance response. Presently, a day-night level summation of single-event doses formulates the cumulative dose; however, a generalization method may improve the understanding of the linkage between multiple single events and cumulative response. This work utilizes an analysis method that employs a parameter to vary the cumulative dose metric such that it can represent the loudest single event, remain as the day-night level summation, or be more responsive to the number of events. The analysis is demonstrated on simulated dose-response datasets derived from previous NASA field studies and from expectations of X-59 community tests. Results demonstrate that certain dose designs are more efficient for exploring the linkage between multiple single events and cumulative response.

Safe dose escalation and reduction of the fraction number of uterine cervical brachytherapy using a gel spacer in the rectovaginal and vesicouterine septum: A planning study

PURPOSETo evaluate the possibility of dose escalation and reduction of fraction number in cervical brachytherapy using a gel spacer. MATERIAL AND METHODSTwenty patients with uterine cervical cancer treated with image-guided adaptive brachytherapy (IGABT) were selected. Hyaluronic acid gel injection (HGI) was performed in the rectovaginal and vesicouterine septum for 10 patients. The other ten patients were not with HGI. Both groups were treated with IGABT involving tandem/ovoid or cylindrical applicators along with additional interstitial needles. Dose distributions approved by radiation oncologists were retrospectively analyzed, and a dose summation of 45 Gy/25 of external beam radiation therapy and IGABT was performed. Dose constraints for D2cc of bladder, rectum, and sigmoid were 80, 70, and 70 Gy, respectively. Equivalent dose in 2-Gy fractions calculations used α/β = 10 Gy for high-risk clinical target volume (CTVHR) D90 and α/β = 3 Gy for organs at risks (OARs). As a planning study, dose distribution rescaling was conducted to deliver as much dose to CTVHR D90 as possible within the dose constraint limitation for OARs when IGABT was performed for four, three, and two fractions in both groups. RESULTSThe median CTVHR D90 was >80 Gy in the non-HGI group and >85 Gy in the HGI group for virtual two and three fractions. Rectum D2cc was significantly lower in the HGI group for three fractions (p < 0.01). CONCLUSIONSIn the HGI group, adequate dose delivery to CTVHR could be achieved with a reduced IGABT fraction number while meeting the dose constraints of OARs.

Influence of Dose Distribution in the Target on the Values of Integral Radiobiological Criteria Based on Synthetic Dose-Volume Histograms

Purpose: To investigate the influence of absorbed dose distribution in the tumor volume on the values of&#x0D; integral radiobiological criteria, such as the probability of local tumor control (Tumor Control Probability, TCP) and normal tissue complication probability (NTCP), based on synthetic dose-volume histograms (DVH), which enables to assess the treatment effectiveness and probability of complications&#x0D; from healthy organs and tissues.&#x0D; Material and methods: Synthetic dose-volume histograms were considered theoretically possible to analyze the dependence of equivalent uniform dose (EUD) on values of Nimirko model parameters and absorbed dose distribution for both tumor and critical organs. The calculation was carried out in Wolfram&#x0D; Mathematica program based on the algorithm, where an array of absorbed dose values per fraction of&#x0D; irradiation volume with step by absorbed dose was calculated for the given values of absorbed dose and&#x0D; the parameter determining the width of distribution. The resulting array was differentiated to obtain&#x0D; the differential DVH. The EUD values were obtained from the normalized differential DVHs.&#x0D; Results: During analysis of EUD value dependence on parameter a values determining degree of nonlinearity of absorbed dose summation in sub-volumes of irradiation and on absorbed dose distribution&#x0D; the following was revealed: for critical organs at high values of parameter a the essential role belongs to&#x0D; high and average values of absorbed dose, and for tumors at low values of parameter a the main role belongs to the minimum value of absorbed dose. Thus, the value of parameter a should be negative for a&#x0D; tumor, and positive for critical organs, and should be specifically defined for specific structures.&#x0D; Conclusion: To improve the predictive value (prediction) of the effect of radiotherapy using the&#x0D; TCP/NTCP Nimirko model, an adequate definition of the parameter a, the value of which can only be determined from absorbed dose distributions over the volume of anatomical structures within clinical trials, is necessary.

Dosimetric Parameters Predictive of Treatment-Related Toxicity in High Dose-Rate Brachytherapy as Monotherapy for Prostate Cancer.

High dose-rate (HDR) brachytherapy as monotherapy is an effective treatment for patients with low- and intermediate-risk prostate cancer and is increasingly being offered as a 2-fraction protocol. There is a lack of consensus on the optimal dosimetric planning parameters to use, or whether there is any benefit summating dosimetric parameters from more than one implant. Our goal is to determine planning parameters associated with disease control, toxicity and health-related quality of life (HRQOL). Data were collected on 83 patients with low- and intermediate-risk prostate cancer who received 2 fractions of 13.5 Gy HDR brachytherapy without androgen-deprivation therapy as part of a randomized phase II clinical trial. An in-house deformable, registration algorithm was used to co-register and dose-summate the plans from both implants for each patient. Acute and late GU and GI toxicities were measured using CTCAE 4.0 and HRQOL was measured in urinary, bowel, sexual and hormonal domains using the EPIC scores. Treatment efficacy was assessed through PSA measurement and imaging with or without biopsy where indicated. Covariates included baseline clinical factors, disease characteristics and treatment dosimetric parameters. Cox proportional hazards was performed to evaluate covariates impact on treatment toxicity and efficacy, and logistic regression analysis evaluated covariates impact on HRQOL. Among the 83 patients, median prostate volume was 46.7cm3. Median summated planning target volume receiving 100% prescription dose (PTV V100%) was 97.4%, median PTV V150% 42.4% and median PTV V200% 15.5%. Median highest dose to the 1cm3 rectum (D1cc) was 66.9% of the prescription dose and median rectum V80% was 0.008cm3. Median urethral D1cc was 99.0% of the prescription dose, median urethral Dmax 121.7% and median urethral D10% 116.2%. Grade ≥2 GI toxicity was uncommon (3.7% acute and 8.5% late), but grade ≥2 GU toxicity was reported in 73.2% (acute) and 46.3% (late) patients. Rectum D1cc and V80% were found to be significantly associated with grade 2 or higher acute GI toxicity, while use of a-blocker at baseline was associated with grade ≥2 acute GU toxicity. Similarly, use of a-blocker was associated with late grade ≥2 GU toxicity, but with no dosimetric associations. No other variables were associated with treatment-related toxicities. Only rectum D1cc was significantly associated with changes in bowel EPIC scores. Estimated 5-year biochemical disease-free survival was 93.9% and 5-year cumulative incidence of local failure was 3.8%. HDR monotherapy with 27 Gy delivered in 2 fractions in treatment of prostate cancer is well tolerated with high rates of disease control and minimal toxicity. Dose summation between 2 fractions of HDR brachytherapy is feasible, with rectal dose predicting acute GI toxicity. The lack of association between dose metrics and urinary toxicity raises the potential for further dose escalation.

Effect of Anesthesia Induction on Cardiac Hemodynamics in Patients Undergoing Durable Left Ventricular Assist Device Implantation: The EACH-LVAD Study.

Right ventricular (RV) dysfunction is common after left ventricular assist device (LVAD) implantation leading to clinical right heart failure (RHF) associated with worsened survival and quality of life. It is likely that intraoperative events such as anesthesia induction play a role in the development or unmasking of RV dysfunction in addition to known effects from hemodynamic changes that occur after LVAD implantation. The EACH-LVAD Study is a prospective, single-center, single-arm, observational cohort study of adult patients with advanced heart failure undergoing durable LVAD implantation with standard anesthesia induction. Intraoperative RV hemodynamics via central venous pressure, mean pulmonary artery pressure, pulmonary artery pulsatility index, and vasoactive-inotropic score (a simple weighted summation of standardized drug doses) and echocardiographic parameters (RV fractional area change, RV area in diastole, RV basal diameter, septum position, RV function, tricuspid regurgitation) were measured and compared at prespecified timepoints, including postinduction. Postoperative clinical RHF was determined based on published definitions. Forty-two patients receiving a first-time LVAD were included between September 2017 and March 2019. Propofol-based induction was used in 31 patients and etomidate-based induction in eight patients. A significant increase in central venous pressure (CVP; p < 0.001), mean pulmonary artery pressure (mPAP; p < 0.001), and vasoactive inotropic score (VIS; p < 0.001) with associated decrease in pulmonary artery pulsatility index (PAPi; p < 0.001) was observed. Right ventricular function worsened throughout. Right heart failure occurred in 70% of patients. Propofol-based induction was not associated with a higher risk of RHF (relative risk [RR], 1.01 [95% confidence interval {CI}, 0.64-1.61]). The EACH-LVAD study demonstrates an effect of anesthesia induction on worsened RV hemodynamics and echocardiographic changes which may have an effect on the development of RHF.

OC-0125 Clinical evaluation of proton therapy of esophageal cancer using dose summation on weekly repeat CTs

OC-0125 Clinical evaluation of proton therapy of esophageal cancer using dose summation on weekly repeat CTs

Sigmoid dose accumulation and reporting for multifractionated brachytherapy for cervical cancer: Methodological development of sigmoid points through virtual endoscopic method

PURPOSEThe sigmoid is an important organ at risk for gynecological brachytherapy (BT). However, the reliability of localization of high-dose regions during multi-fractionated treatment is limited. This work reports the methodological development of sigmoid points to summate multi-fractionated doses. METHODS AND MATERIALTen paired MRI data sets of ring-based intracavitary brachytherapy were obtained. Simulating a virtual endoscope, a reference line was created along the central axis of the anorectosigmoid for each implant. A trendline was generated, and linear dose was determined. Three-dimensional (3D) coordinates of high-dose regions were identified, and overlap was determined. In the next step, 3D coordinates of high-dose sigmoid points were localized in reference to cervical os and re-verified for location in reference to sigmoid lumen and corroboration with 2cc doses. With minor modifications, sigmoid points were proposed. RESULTSIn 6 of 10 patients, high-dose regions co-localized in subsequent fractions of BT. Three high-dose regions were identified along the sigmoid length and proposed as sigmoid points in reference to cervical os. (S1’= 0.5 cm right, 1.5 cm posterior, and 2.4 cm cranial; S2’ = 0.3 cm anterior and 4.5 cm cranial; S3’ = 2.7 cm left, 3 cm anterior, and 3.6 cm cranial to the cervical os). S1’ and S2’ were located in the sigmoid in 70% and 60% of data sets. The mean difference between D2cc and S1’/S2’ was 0.30 Gy and 1.06 Gy respectively. S3’ had limited corroboration to sigmoid lumen or 2 cc doses. The points S1’ and S2’ were further modified (minor) for applicability and proposed as sigmoid points 1 and 2 (SP1 0.5 right,1.5 posterior and 2.5 cm cranial to cervical os and SP2 (0.5 cm anterior and 4.5 cm cranial to cervical os)). CONCLUSIONSP1 and SP 2 are proposed as a surrogate for 2 cc sigmoid doses and may provide a method of reliable inter-fraction dose summation. This pilot work requires further validation.

Dose accumulation for MR-guided adaptive radiotherapy: From practical considerations to state-of-the-art clinical implementation.

MRI-linear accelerator (MR-linac) devices have been introduced into clinical practice in recent years and have enabled MR-guided adaptive radiation therapy (MRgART). However, by accounting for anatomical changes throughout radiation therapy (RT) and delivering different treatment plans at each fraction, adaptive radiation therapy (ART) highlights several challenges in terms of calculating the total delivered dose. Dose accumulation strategies-which typically involve deformable image registration between planning images, deformable dose mapping, and voxel-wise dose summation-can be employed for ART to estimate the delivered dose. In MRgART, plan adaptation on MRI instead of CT necessitates additional considerations in the dose accumulation process because MRI pixel values do not contain the quantitative information used for dose calculation. In this review, we discuss considerations for dose accumulation specific to MRgART and in relation to current MR-linac clinical workflows. We present a general dose accumulation framework for MRgART and discuss relevant quality assurance criteria. Finally, we highlight the clinical importance of dose accumulation in the ART era as well as the possible ways in which dose accumulation can transform clinical practice and improve our ability to deliver personalized RT.

Evaluation of Repeated Lung Stereotactic Body Radiotherapy Using a Radiotherapy Dose Accumulation Routine

<h3>Purpose/Objective(s)</h3> Repeated lung SBRT has been used for recurrent or metachronous non-small-cell lung cancer. Comprehensive evaluation of cumulative dose is essential for safe reirradiation to minimize the risk of pneumonitis and esophageal toxicity. We evaluated an in-house script named RADAR (Radiotherapy Dose Accumulation Routine) designed to provide accurate dose assessment that accounts for registration uncertainties, and improve the efficiency of clinical workflow. <h3>Materials/Methods</h3> In this pilot study, we analyzed a cohort of 20 patients who underwent 2-5 courses of repeated lung SBRT. Lung volume changed 8±8% between courses. Planning CT images from earlier treatment courses were registered onto the final course in two steps: first, a rigid registration based on alignment of spine and rib cage, then a deformable image registration (DIR) using a ‘demons' algorithm in a planning system. The resulting deformable vector fields were used by RADAR to transform voxels for automated dose accumulation. User can choose to output either physical dose or equivalent dose in 2Gy fractions (EQD2, α/β=3) with a discount factor (Paradis, ARO 2019). RADAR provides three approaches for dose accumulation: 1) direct sum that outputs voxel level dose summation; 2) unrestricted search that incorporates DIR uncertainty by conservatively assigning the maximum dose within a search radius (3mm) to the voxel of interest for dose accumulation; 3) restricted search, which performs the same dose accumulation as in 2) but imposes structure label matching in the search radius, therefore including only voxels within the same structure. Accumulated dose distribution was written back to the planning system for evaluation. We extracted mean lung dose (MLD) and esophagus D5cc (EsoD5cc) with respect to various accumulation approaches for comparison. <h3>Results</h3> MLD and EsoD5cc were significantly higher when accounting for DIR uncertainties (<i>p</i><0.001 two-tailed t-test). MLD has less uncertainty than EsoD5cc due to its averaging nature. For radiotherapy with >2 courses, RADAR considerably shortened the processing time by auto-accumulating dose from multiple courses simultaneously, as opposed to the cumbersome manual approach of creating plan sums iteratively. Typical time for dose accumulation and evaluation using RADAR is < 10 mins. <h3>Conclusion</h3> RADAR is a convenient and efficient tool to calculate and evaluate cumulative dose for lung reirradiation cases. It identifies higher OAR doses due to dose accumulation uncertainties, for example coming from the registration. Our study provides initial data to establish clinical guidance for design and optimization of repeated lung SBRT.

On the operational quantity for eye lens neutron dosimetry considering ICRU 95 report

For planned occupational exposure situations, the International Commission on Radiological Protection (ICRP) publication 118 recommends an equivalent dose limit for the lens of the eye of 20 mSv yr−1 averaged over 5 yr with no single year exceeding 50 mSv. Regulatory authorities of various jurisdictions worldwide followed some or all, of the ICRP recommendations and implemented reduced occupational lens of eye dose limits in their legislation. As compliance with the eye-lens dose limit will be based on the summation of doses received from all types of radiation, applicable to a variety of workplaces, the contribution of neutrons to eye lens dose will be important where it contributes a significant fraction of the total dose to the eye lens. This work presents and discusses computed personal absorbed dose (D lens/Φ), and personal dose equivalent (H p(3)/Φ) as well as a newly proposed relative biological effectiveness (RBE)-weighted absorbed dose (RBE × D lens/Φ) conversion coefficients for the lens of the eye for neutron exposure at incident energies from thermal to ∼20 MeV. The D lens/Φ coefficients were obtained from a simulation model developed for this study that contains the stylised eye model embedded in the adult UF-ORNL mathematical phantom. The modelling techniques used in these simulations were also used to calculate H p(3)/Φ for the International Commission on Radiation Units and Measurements (ICRU) slab and cylinder phantoms. All simulations carried out for this study utilised the Monte Carlo N-Particle (MCNP) series of codes. The results are compared with the related published data. The issue of compliance with the current equivalent dose limit for the lens of the eye is addressed from a neutron perspective considering the recent proposed redefinition of the operational quantities for external radiation exposure in ICRU report 95. The use of a radiation weighted absorbed dose (RBE × D lens, in Gy) is proposed for the tissue reactions in the eye-lens for neutron radiation as per the National Council on Radiation Protection and Measurements report 180, and in line with the recent review and revision of the System of Radiological Protection To Keeping the ICRP Recommendations Fit for Purpose, which states that RBE weighted dose should be used for high-Linear energy transfer (LET) radiations such as neutrons. This confirms the earlier statement in ICRP publication 92, paragraph 297 and reiterated in the Executive summary, paragraph (q) of ICRP publication 118. The proposed approach would provide an operational quantity consistent with the units of the new eye-lens dose limits without being overly conservative.

Dose Accumulation for Multicourse Gynecological Reirradiation: A Methodological Narrative and Clinical Examples

Reirradiation (re-RT) is a suitable and potentially curative treatment option for in-field locoregional recurrences in gynecological malignancies. Lack of clear guidelines on prescription, dose-response relationship, and clinical outcomes limits its clinical use. This clinical narrative describes the methodology for integration of deformable image registration (DIR) for cumulative dose assessment in the setting of re-RT for gynecologic malignancies, using the tools available within a commercial treatment planning system. Four patients who received re-RT for locoregional recurrence or second cancer within previously irradiated areas for a gynecologic primary were identified. Patient-specific DIR for deformable dose mapping and accumulation was retrospectively performed using intensity-based algorithm provided by the Varian Medical Systems Velocity AI version 4.1. Cumulative equivalent doses in 2 Gy fractions (EQD2) delivered to overlapping targets and organs at risk were generated and compared with the physically summated doses. For both approaches, brachytherapy (BT) component was physically summated in cases where the BT applicator caused significant anatomic distortion. The mean maximum cumulative overlapping target dose was 119.4 Gy10 (range, 84.7 Gy10-144.9 Gy10). The mean cumulative doses received by 2 cm3 of bladder, rectum, sigmoid, and bowel were 114.6 Gy3 (101.1-133.4 Gy3), 98.7 Gy3 (67-136.2 Gy3), 92.5 Gy3 (70.4-107 Gy3), and 89.9 Gy3 (81.1-102.8 Gy3), respectively. In the setting of in-field nodal recurrence, DIR-based dose summation was associated with lower cumulative organs at risk doses than those estimated with physical summation, except in one case with a higher bowel dose. In cases where re-RT was given for local recurrence/second primary, variation in sigmoid doses was observed between the 2 dose-summation strategies across all 3 cases, but it was inconsistent with bladder, rectum, or the bowel. DIR-based dose accumulation can be used to guide re-RT planning and can provide clinically relevant information, especially in cases with nodal recurrences. Registration of BT data sets remain challenging and requires an individualized assessment when applying these algorithms to clinical practice.

PD-0396 Robust dose summation to evaluate diaphragm motion impact in proton therapy of esophageal cancer

PD-0396 Robust dose summation to evaluate diaphragm motion impact in proton therapy of esophageal cancer

Abstract P2-12-08: Impact of summation dose intensity product on pathologic response in patients receiving neoadjuvant chemotherapy for early breast cancer

Abstract Background: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is associated with beneficial long-term outcome in early breast cancer (EBC). pCR is defined as ypT0/is, ypN0. It is well known that pCR rates depend on tumor subtype. However, the impact of different therapy regimens, dose delays and dose reductions on pCR rates is still unclear. This retrospective study analyzed the therapy dose of patients with pCR and non-pCR after NACT for EBC using referenced and delivered summation dose intensity product (SDIP) and relative dose intensity (RDI) calculations. Methods: SDIP of different therapy regimens were calculated by defining a unit dose intensity (UDI) for each therapy (Hryniuk et al. JCO 1998). The UDI is defined as the dose in mg/m2/week that produces a 30% complete or partial remission rate as a single agent in first-line therapy for metastatic breast cancer. For each regimen, the planned dose intensities (PDI) were divided by the UDI for every single drug. The summation dose intensity (SDI) is the addition of the resulting decimal fractions. Multiplying the SDI by the treatment intervals and number of cycles gives the SDIP. SDIP can be divided into referenced SDIP (rSDIP) and delivered SDIP (dSDIP). RDI is the ratio of dSDIP in comparison to rSDIP. Therapy dose calculations were performed for patients who received NACT for EBC at the National Center for Tumor Diseases (NCT) Heidelberg, Germany, between 01/2015 and 08/2019. Results: 590 patients (median age 51 years) were included, median follow up was 38 months, 225 patients (38.1%) achieved pCR. 65 patients (11.0%) were hormone receptor positive HER2 negative (HR+HER2-), 164 (27.8%) were HR-HER2-, 133 (22.5%) were HR+HER2+, 97 (16.4%) were HR-HER2+. Significant difference between the pCR and non-pCR group was observed for HR-status (p&amp;lt;0.001), HER2-status (p&amp;lt;0.001), tumor grading (p&amp;lt;0.001) and Ki-67 (p&amp;lt;0.001). Age of diagnosis (p=0.611), menopause-status (p=0.769), tumor size (p=0.183) and nodal status (p=0.163) did not significantly vary between patients with pCR versus non-pCR. Patients with pCR had significantly higher rates of anemia II° (p=0.006). No significant difference was seen for anemia ≥III°, neutropenia ≥II°, deviation of liver enzymes ≥II°, nephrotoxicity ≥II°, polyneuropathy ≥II° or the administration of red cell and platelet concentrate as well as the use of Granulocyte-Colony Stimulating Factor (G-CSF). 3 year overall survival (OS), metastasis-free survival (MFS) and recurrence-free survival (RFS) were found to be significantly better in patients with pCR (OS: 98.0% vs. 90.2%, p&amp;lt;0.001; MFS: 94.5% vs. 84.6%, p&amp;lt;0.001; RFS: 97.7% vs. 94.0 %, p=0.029). Patients with pCR had a significantly higher mean rSDIP (69.8 vs. 58.9, p=0.001) and dSDIP (59.5 vs. 49.1, p=0.001). Mean RDI did not significantly vary between pCR and non-pCR (0.853 vs. 0.840, p=0.350). Mean rSDIP and dSDIP significantly vary between the tumor subtypes HR+HER2-, HR-HER2-, HR+HER2+, and HR-HER2+ (rSDIP: 47.4, 54.5, 74.3, 76.7; p&amp;lt;0.001; dSDIP: 39.5, 43.3, 62.0, 67.0; p&amp;lt;0.001). Mean rSDIP and dSDIP did not significantly vary between patients with pCR and non-pCR within the tumor subtypes. Conclusion: Outcomes for NACT are consistent with published data concerning pCR rates. It is notable that the pCR group had significantly higher rSDIP and dSDIP than the non-pCR group whereas RDI and toxicity did not significantly vary between the two groups. rSDIP and dSDIP were mainly depending on the tumor subtype. This data confirms that the tumor subtype has a major impact on pCR rate. Whilst this retrospective analysis must be interpreted with caution, the results show that SDIP is an integral parameter for assessing the efficacy and adequate application of combination therapy and is associated with pCR rate and overall survival. Citation Format: Thomas M Deutsch, Michelle Kobel, Manuel Feisst, Fabian Riedel, Katharina Smetanay, Carlo Fremd, Laura Michel, Michael Golatta, Joerg Heil, Markus Wallwiener, Andreas Schneeweiss. Impact of summation dose intensity product on pathologic response in patients receiving neoadjuvant chemotherapy for early breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-12-08.