Normal Tissue Dose Constraints Research Articles

Dosimetric comparison of proton therapy and CyberKnife in stereotactic body radiation therapy for liver cancers

Stereotactic body radiation therapy (SBRT) has been increasingly used for the ablation of liver tumours. CyberKnife and proton beam therapy (PBT) are two advanced treatment technologies suitable to deliver SBRT with high dose conformity and steep dose gradients. However, there is very limited data comparing the dosimetric characteristics of CyberKnife to PBT for liver SBRT. PBT and CyberKnife plans were retrospectively generated using 4DCT datasets of ten patients who were previously treated for hepatocellular carcinoma (HCC, N = 5) and liver metastasis (N = 5). Dose volume histogram data was assessed and compared against selected criteria; given a dose prescription of 54 Gy in 3 fractions for liver metastases and 45 Gy in 3 fractions for HCC, with previously published consensus-based normal tissue dose constraints. Comparison of evaluation parameters showed a statistically significant difference for target volume coverage and liver, lungs and spinal cord (p < 0.05) dose, while chest wall and skin did not indicate a significant difference between the two modalities. A number of optimal normal tissue constraints was violated by both the CyberKnife and proton plans for the same patients due to proximity of tumour to chest wall. PBT resulted in greater organ sparing, the extent of which was mainly dependent on tumour location. Tumours located on the liver periphery experienced the largest increase in organ sparing. Organ sparing for CyberKnife was comparable with PBT for small target volumes.

A Dosimetric Comparative Study of Carbon-Ion Radiotherapy Versus X-ray Volumetric Modulated Arc Therapy for Stage III Non-Small-Cell Lung Cancer.

Compared to photon beam, carbon-ion radiotherapy (CIRT) has both physical and biological advantages. To examine whether two-dimensional (2D) CIRT is dosimetrically superior to photon beam volume-modulated arc therapy (VMAT) in protecting the normal tissues for stage III non-small-cell lung cancer (NSCLC). A retrospective study was conducted. Thirteen patients with stage III NSCLC treated in our center with curative CIRT and a sham photon beam VMAT treatment planning with the same normal tissue dose constraints were included for analysis. Target dose distributions and the homogeneity index (HI) within the planning target volumes were compared. Both CIRT and VMAT plans have good tumor coverage with no significant differences in D98, D95, and D50 of Planning target volume 1 (PTV1) between the two plans. The HIs between the two plans are similar. The HI of PTV2 is superior in the CIRT plan (CIRT vs. VMAT: 0.08 vs. 0.16, P < 0.05). In general, CIRT results in a lower dose of the organ-at-risk (OAR) than the photon plans. The V5, V10, V20, V30, V40, and Dmean of the contralateral lung in the CIRT plan are significantly lower than that of the photon VMAT. For the ipsilateral lung, the V5 of CIRT is significantly lower. The CIRT also had significantly lower spinal cord Dmax, esophageal Dmean and V50, V10 and V30 of bone, and V50 of the trachea and bronchial tree. Compared with photon VMAT, 2D-CIRT using the passive beam scanning technique significantly reduces the radiation dose to the OARs in curative radiotherapy of stage III NSCLC, suggesting a better protection of the normal tissues.

Phase I-II Study of Prone Hypofractionated Accelerated Breast and Nodal Intensity Modulated Radiation Therapy

In patients (pts) with breast cancer, prone radiation therapy (RT) has been shown to reduce heart and lung dose which may decrease late toxicity. Routinely used for whole breast irradiation, its use to treat regional lymph nodes (LNs) is not widespread. In this phase I-II study, pts treated with partial mastectomy or mastectomy with 1-5 pathologically involved LNs underwent whole breast or post-mastectomy RT plus regional nodal irradiation using IMRT to the supraclavicular and level III axillary LNs. Pts who underwent sentinel LN biopsy (SLNB) alone (no axillary dissection) had the level I and II axillary LNs included in the RT field. 40.5Gy in 15 daily 2.7Gy fractions with daily concomitant 0.5Gy tumor bed boost was prescribed. Normal tissue dose constraints included heart V5Gy<5%, ipsilateral lung V10Gy<20%, contralateral lung V5Gy<15%, ipsilateral brachial plexus (BP) maximal dose (Dmax)<43Gy, spinal cord Dmax≤37.5Gy, spinal cord + 0.5cm Dmax<41Gy, thyroid contralateral lobe Dmax<16Gy, esophagus V30Gy<50% and Dmax≤40.5Gy. The primary endpoints were dosimetric feasibility and incidence of >grade 2 acute toxicity according to CTCAE, v3.0. The secondary endpoint was late toxicity. Exploratory outcomes were local recurrence, disease free survival (DFS), and overall survival (OS). Between January 2011 to December 2016, 97 pts with stage IB-IIA breast cancer were enrolled. 66 pts underwent partial mastectomy and 31 pts underwent mastectomy. 16 pts had SLNB alone. 33% (95% CI: 23.8%, 43.3%) met all protocol dose constraints. Heart, contralateral lung, spinal cord and esophagus V30Gy constraints were met by all pts. The ipsilateral lung constraint was met in 95% (95% CI: 88.6%, 98.4%) of plans with a mean V10Gy of 9.44% (SD: 6.08). The BP Dmax constraint was exceeded in 31.6% (95% CI: 22.4%, 41.9%) of plans with a mean increase of 2.86 Gy (SD: 7.92 Gy) over target. The esophageal Dmax<40.5Gy constraint was exceeded in 6 plans with an increase in 0.74 Gy (SD: 0.46 Gy) over target. There were no grade 3 acute toxicities meeting the primary toxicity endpoint. Common acute low-grade toxicities by pt included fatigue (grade 1: 54 [56%]; grade 2: 2 [2%]), esophagitis (grade 1: 8 [8%]; grade 2: 2 [2%]), dermatitis (grade 1: 81 [84%]; grade 2: 6 [6%]). At median and maximum follow up of 8.02 (IQR: 3.31) and 13.3 years, respectively, there were 2 local recurrences (2.1%). DFS and OS were 86.6% (95% CI: 78.2%, 92.7%) and 90.7% (95% CI: 83.1%, 95.7%), respectively. The incidence of pts with maximum grade 1, 2 and 3 late toxicities were 39 (40%), 14 (14%), and 2 (2%), respectively. The maximum grade late toxicities included 1 grade 3 retraction and 2 grade 3 asymmetries. There was no brachial plexopathy or pneumonitis. Patients treated with prone hypofractionated hybrid breast/chest wall tangents and IMRT to the regional LNs demonstrate excellent dosimetry to the heart, lungs and spinal cord, minimal acute and late toxicity and excellent clinical outcomes. PMID: 26723552.

Trimodal Therapy Using an MR–guided Radiation Therapy Partial Bladder Tumor Boost in Muscle Invasive Bladder Cancer

Bladder preservation with trimodal therapy (TMT; maximal tumor resection followed by chemoradiation) is an effective paradigm for select patients with muscle invasive bladder cancer. We report our institutional experience of a TMT protocol using nonadaptive magnetic resonance imaging-guided radiation therapy (MRgRT) for partial bladder boost (PBB). A retrospective analysis was performed on consecutive patients with nonmetastatic muscle invasive bladder cancer who were treated with TMT using MRgRT between 2019 and 2022. Patients underwent intensity modulated RT-based nonadaptive MRgRT PBB contoured on True fast imaging with steady state precession (FISP) images (full bladder) followed sequentially by computed tomography-based RT to the whole empty bladder and pelvic lymph nodes with concurrent chemotherapy. MRgRT treatment time, table shifts, and dosimetric parameters of target coverage and normal tissue exposure were described. Prospectively assessed acute and late genitourinary and gastrointestinal (GI) toxicity were reported. Two-year local control was assessed with Kaplan-Meier methods. Seventeen patients were identified for analysis. PBB planning target volume margins were ≤8 mm in 94% (n=16) of cases. Dosimetric target coverage parameters were favorable and all normal tissue dose constraints were met. For MRgRT PBB fractions, median table shifts were 0.4 cm (range, 0-3.15), 0.45 cm (0-2.65), and 0.75 cm (0-4.8) in the X, Y, and Z planes, respectively. Median treatment time for MRgRT PBB fractions was 9 minutes (range, 6.9-17.4). We identified 32 out of 100 total MRgRT fractions that may have benefitted from online adaptation based on changes in organ position relative to planning target volume, predominantly because of small bowel (13/32, 41%) or rectum (8/32, 25%). Two patients discontinued RT prematurely. The incidence of highest-grade acute genitourinary toxicity was 1 to 2 (69%) and 3 (6%), whereas the incidence of acute GI toxicity was 1 to 2 (81%) and 3 (6%). There were no late grade 3 events; 17.6% had late grade 2 cystitis and none had late GI toxicity. With median follow-up of 18.2 months (95% CI, 12.4-22.5), the local control rate was 92%, and no patient has required salvage cystectomy. Nonadaptive MRgRT PBB is feasible with favorable dosimetry and low resource utilization. Larger studies are needed to evaluate for potential benefits in toxicity and local control associated with this approach in comparison to standard treatment techniques.

A Survey of Pediatric Clinical Trial Radiotherapy Dose Constraints

<h3>Purpose/Objective(s)</h3> Radiation therapy normal tissue dose constraints are critical when treating children with cancer due to the vulnerability of developing organs to toxicity and the many years over which these effects can evolve. Guidelines in international clinical trials have been instrumental in shaping how treatment plans are designed; however, consistency among organs at risk (OARs) constraints has not been previously evaluated. In this study we identify the variations in OAR-specific dose constraints within pediatric trials both in the United States (US) and in Europe. <h3>Materials/Methods</h3> All US pediatric trials from the COG website were included up until 1/1/2020 along with a sampling of European trials accessible in the Netherlands. Dose constraints were identified and built into an interactive web application with filters to display data by OAR, protocol, dose, volume, and fractionation scheme. Dose constraints were compared between pediatric US and European trials by graphical intercomparison and by comparing high dose constraints (maximum dose [Dmax] or dose to a volume ≤ 20%) and by dose metrics that were commonly used across protocols. <h3>Results</h3> Sixty-five trials were included with the US trials (53) represented by the COG/CCG/POG and the European trials (12) represented by the SIOP, EURAMOS, GPOH, DCOG, and EpSSG. Thirty-three separate OARs were found with high variability within the trials for each OAR, ranging from different maximum tolerable doses to variations of volumetric dose constraints. Seven organs had 10 to 18 different constraints and included serial organs such as the spinal cord, optic chiasm, optic nerves, and brainstem as well as parallel organs including the lungs, liver, and heart. An example of dose variability can be seen with the spinal cord Dmax constraint ranging from 50 Gy to V59 < 10%, the optic nerves constraint ranging from a Dmax of 45 Gy to 60 Gy, the heart V30 constraint ranging from 40-100%, and the kidney D50% constraint ranging from 8-24 Gy. When comparing high dose tolerances between US and European trials, US constraints were higher for four OARs—bladder (V70 < 20% vs Dmax < 60), lungs (V20 < 20% vs Dmax < 18), mandible (V77 < 1cc vs Dmax < 60), and spinal cord (V57 < 10% vs Dmax < 54); lower for four OARs—brainstem (V63 < 10% vs V64 < 10%), heart (Dmax < 30 vs Dmax < 30.6), kidneys (Dmax < 15 vs Dmax < 19.8), and liver (Dmax < 15 vs Dmax < 23.4); and identical in four OARs—brain, optic chiasm, optic nerves, and bowel. <h3>Conclusion</h3> Review of pediatric dose-volume constraints in clinical trials showed substantial variability for all OARs. Continued focus on standardization of OAR dose constraints and risk profiles are essential to improving clinical trial consistency and improving understanding of dose-response in the pediatric population.

Ramifications of Setup Margin Use During Frameless Stereotactic Radiosurgery/Therapy With Gamma Knife Icon Cone-Beam Computed Tomography (CBCT): A Dosimetric Study.

ObjectiveThe objective is to explore the possibility of optimal/rational application of setup margin during treatment planning for frameless stereotactic Gamma Knife radiosurgery/therapy.MethodsUncertainty measurements for frameless Gamma Knife Icon treatment were used to calculate the necessary setup margin via four different published recipes and these margins were subsequently applied to treatment plans of 30 previously treated patients and replans were generated meeting comparable plan quality metrics. All plans were then analyzed based on the ability to maintain normal tissue dose tolerances and the relative increase in target dose coverage probability using a pass/fail scoring system based on published normal tissue dose constraints and an in-house developed optimal scoring method.ResultsGross tumor volume/planning target volume (GTV/PTV) size strongly correlated with both meeting normal tissue tolerances and optimal scores for single fraction plans corroborating published clinical outcomes. The Van Herk Margin Formula (VHMF) and Parker margin formulae were indicated as good candidates for high probabilities of both meeting normal tissue goals and high optimal scores which generally translated to just over 1 mm in GTV to PTV margin.ConclusionFor single fraction treatment, GTV size is highly significant in predicting failure to meet normal tissue goals whereas whether setup margin was used was not a significant predictor. Setup margin can rationally be applied when fraction number is dictated by clinically indicated metrics regarding GTV size of greater or less than 4 cc. 1 mm is a reasonable practical application of margin added to GTV to ensure physical prescription dose target coverage for most cases when clinically desired based on disease type and intended outcome.

Trigger-Based Adaptive Planning to Reduce Bowel Dose in Patients Receiving Radiotherapy for Anal Cancer

<h3>Purpose/Objective(s)</h3> Standard of care for locally advanced anal carcinoma is definitive chemoradiation with IMRT. Currently, target and organ-at-risk (OAR) volumes are created using a pre-treatment CT-simulation scan. However, during the course of radiotherapy, there is often change in the size and/or position of the tumor and surrounding normal structures. Therefore, we hypothesize that the implementation of an adaptive radiation therapy treatment protocol in anal cancer may reduce radiation dose to critical surrounding normal structures, such as the bowel, through the use of anatomy-adapted replanning. <h3>Materials/Methods</h3> Retrospective daily adaptive CTs were created for 4 patients (54 Gy, 30 fraction VMAT) in an oncology imaging informatics system using the Adaptive Calculation and Tracking for Offline Plan Review (ACTOR) toolkit. Each adaptive CT was created by deformable image registration (dir) of the planning CT to the daily CBCT. The structure sets from the planning CT were deformed onto each adaptive CT and ultimately corrected and revised by two qualified radiation oncologists. The adaptive CTs were transferred to a treatment planning system for recalculation. The original treatment plan was recalculated on each fraction adaptive CT to establish the real dose received during treatment. A two-sample t-test was used to compare the average real dose received dosimetric values to the values obtained on trigger-based adaptive planning. <h3>Results</h3> Using dose prescriptions for target volumes and normal tissue dose constraints as defined in RTOG 0529 (Kachnic et al 2013), normal bowel dose metrics, including bowel V45 < 20cc, were tracked as possible triggers for adaptation. Using bowel V45 > 20cc as trigger 1, there was a significant reduction in bowel V45 for each patient (table), with an average reduction in bowel V45 of 86.7% (<i>P</i> = 0.0001) across all patients. Adapting only the 5 fractions with the highest values for bowel V45 (trigger 2), we also found a significant reduction for each patient (table), with an average reduction of 20.8 % (<i>P</i> = 0.0011) across all patients. <h3>Conclusion</h3> Our study demonstrated that triggered adaptive re-planning using bowel V45 > 20cc could likely achieve reductions in normal tissue dose. Adaptive planning during radiation treatment of anal cancer may therefore be beneficial for reduction of treatment-related GI toxicity. These results can help inform a future randomized trial of adaptive therapy vs. standard planning.

Tangential VMAT vs. 3D-Conformal Radiotherapy for Left-Sided Whole Breast and Regional Lymph Node Irradiation

<h3>Purpose/Objective(s)</h3> Whole breast and regional nodal irradiation presents a challenge in balancing the need for target coverage with avoidance of normal tissues. The novel technique termed tangential VMAT (tVMAT) utilizes beam angles tangential to the curvature of the chest wall without beams entering perpendicular to the chest wall in the direction of thoracic organs. In this study tVMAT was compared to standard 3D-conformal radiotherapy (3DCRT) in a dosimetric analysis. To our knowledge this is the first study to assess tVMAT in left-sided breast cancer patients requiring regional nodal irradiation. <h3>Materials/Methods</h3> Ten patients with left-sided breast cancer previously treated with adjuvant RT to the breast, axillary, and supraclavicular nodal regions were selected for this study. For each patient two plans were created: 1) a standard dual-isocenter three-field 3DCRT plan (two tangents and a supraclavicular field) using field-in-field dose modulation and 2) a tVMAT plan. Each tVMAT plan utilized a single isocenter for two partial arcs with angles selected to keep the central axis of the beams tangential to the curvature of the chest wall at all points. The prescription for both techniques was 5000 cGy in 25 fractions to the breast, axillary levels I-III, and supraclavicular target volumes with a goal coverage of 95% of the breast and nodal target volumes receiving at least 95% of the prescription dose. Normal tissue dose constraints were adapted from NSABP B51. Plans were created using a treatment planning system and differences in mean values for dosimetric endpoints were assessed for statistical significance using a Student's t-test (α = 0.05). <h3>Results</h3> Compared to 3DCRT plans, tVMAT provided more uniform coverage to the breast and regional lymph nodes (mean conformity index was 1.38 for tVMAT versus 2.42 for 3DCRT, <i>P</i> < 0.01) and the max point dose for tVMAT was lower on average (112.8% for tVMAT versus 121.5% for 3DCRT, <i>P</i> < 0.001). Both plans met the breast target coverage goals, however coverage to the lymph nodes was superior for tVMAT (mean coverage to 95% of the axillary plus supraclavicular target volumes was ≥ 99.0% of the prescribed dose for tVMAT versus ≥ 94.8% for 3DCRT, <i>P</i> < 0.001). Cold spots within the breast and nodal target volumes were on average lower for 3DCRT (952 cGy for 3DCRT versus 2760 cGy for tVMAT, <i>P</i> < 0.001). OAR sparing was improved with tVMAT, with a lower average V20_Gy for the left lung (16.5% for tVMAT versus 24.6% for 3DCRT, <i>P</i> < 0.01), and lower mean heart dose (168 cGy for tVMAT versus 200 cGy for 3DCRT, <i>P</i> = 0.03). <h3>Conclusion</h3> Tangential VMAT is a promising technique for the treatment of intact breast and regional lymph nodes and may provide better target coverage and OAR sparing compared to conventional 3D-conformal techniques. The use of a single isocenter for tVMAT could yield a simplified setup and more accurate treatment delivery, ideally with the use of deep inspiration breath hold or respiratory gating.

The Impact of Radiotherapy Protocol Adherence on the Treatment Outcome in Patients With Locally Advanced NSCLC Treated With Concurrent Chemoradiation: Results From the Radiotherapy Quality Assurance of the International Randomized PET-Plan Trial

The success of intensification and personalization of the curative treatment of non-small cell lung cancer (NSCLC) is strongly associated with the precision in radiotherapy (RT) treatment, which must therefore follow high standards. Herein we evaluate the impact of RT protocol adherence in the prospective international multicenter trial on curative treatment of NSCLC.In the open-label, randomized, controlled PET-Plan trial, patients with inoperable NSCLC were randomized at a 1:1 ratio regarding the target volume delineation informed by ¹⁸F-FDG PET and CT plus elective nodal irradiation (Arm A) or target volumes informed by PET alone (Arm B) and received iso-toxically dose-escalated concurrent chemoradiation. The prospectively organized quality assurance program (RTQA) included individual case review by predefined criteria. 24 items (arm A) and 20 items (arm B) were scored as per protocol (pP), minor (miD), intermediate (inD) and major (maD) deviation by a multicenter panel of radiation oncologists and medical physicists.Between 05/2009 and 11/2016, 205 patients were randomized, (one patient was excluded after randomization), 173 were treated per-RT protocol and 31 (15%) patients had maD. Patients with maD had an inferior overall survival (OS) (HR 2.9, 95% CI 1.8-4.4, P < .0001) as well as a higher risk of loco-regional progression (HR 5.7, 95% CI 2.7-11.1, P < .0001). Especially, patients with maD concerning normal tissue delineation and/or dose constraints had a worse OS (HR 3.6, 95% CI 1.5-7.3, P = 0.006) although there was no impact on the incidence of toxicities. Adjusting for the UICC stadium and the gross tumor volume as prognostic factors, the effects remained similar.Non-adherence to the RT protocol was associated with an inferior OS and loco-regional control. These results underline the importance of RTQA.

Predicting the Clinical Gains Associated With Further Reduction of Normal Tissue Dose Constraints in Oropharynx Cancer Radiotherapy

<h3>Purpose/Objective(s)</h3> Toxicity mitigation is a salient focus in the treatment of HPV-associated oropharyngeal cancer. As the standard of care evolves, toxicity mitigation can be facilitated by adopting more stringent normal tissue constraints. We hypothesize that further reduction in currently accepted constraints leads to reductions in normal tissue complication probabilities (NTCP) without compromising disease outcomes. <h3>Materials/Methods</h3> This was a retrospective, single-institution study of patients with oropharynx cancer treated with adjuvant volumetric modulated arc therapy to standard doses (60-66 Gy) and volumes (i.e., bilateral neck) from 2015-2018. Doses delivered to organs at risk were compared to recommended dose acceptance criteria from a recent, cooperative trial of RT to 60 Gy (NRG HN002). We applied validated, published NTCP models for xerostomia, dysphagia, dysgeusia, oral mucositis and esophagitis relevant to oropharyngeal cancer. <h3>Results</h3> 92 patients were identified. Median follow-up was 2.2 years. The doses achieved and corresponding estimates of NTCP are shown in Table 1, as compared to a nationally recognized standard (NRG HN002). Notable NTCP reductions were observed for salivary flow, dysphagia, dysgeusia, mucositis, and esophagitis. The use of more stringent constraints did not impact disease outcome, with only a total of 3 patients having experienced locoregional recurrence (1 local, 2 regional), for an overall locoregional control of 96.7%. <h3>Conclusion</h3> Improved normal tissue sparing compared to current dose constraint standards is achievable with contemporary RT planning techniques. These improved constraints may lead to decreased toxicity, while preserving excellent disease outcomes. Our constraints can easily be adopted as standard of care and used in conjunction with other efforts to mitigate toxicity.

Normal tissue tolerance amongst paediatric brain tumour patients- current evidence in proton radiotherapy.

Proton radiotherapy (PT) is used increasingly for paediatric brain cancer patients. However, as demonstrated here, the knowledge on normal tissue dose constraints, to minimize side-effects, for this cohort is limited. A search strategy was systematically conducted on MEDLINE® database. 65 papers were evaluated ranging from 2013 to 2021. Large variations in normal tissue tolerance and toxicity reporting across PT studies makes estimation of normal tissue dose constraints difficult, with the potential for significant late effects to go unmeasured. Mean dose delivered to the pituitary gland varies from 20 to 30 Gy across literature. Similarly, the hypothalamic dose delivery ranges from 20 to 54.6 Gy for paediatric patients. There is a significant lack of radiobiological data for paediatric brain cancer patients undergoing proton therapy, often using data from x-ray radiotherapy and adult populations. The way forward is through standardisation of reporting in order to validate relevant dose constraints.

Impact of radiotherapy protocol adherence in NSCLC patients treated with concurrent chemoradiation: RTQA results of the PET-Plan trial

IntroductionThe success of intensification and personalisation of the curative treatment of non-small cell lung cancer (NSCLC) is strongly associated with the precision in radiotherapy. Here, we evaluate the impact of radiotherapy protocol adherence in a prospective multicentre trial. MethodsIn the open-label, randomised, controlled PET-Plan trial, patients with inoperable NSCLC were randomized at a 1:1 ratio regarding the target volume delineation informed by 1F-FDG PET and CT plus elective nodal irradiation (arm A) or target volumes informed by PET alone (arm B) and received iso-toxically dose-escalated concurrent chemoradiation. The prospectively organised quality assurance program (RTQA) included individual case review by predefined criteria. For evaluation, protocol adherence was scored as per protocol (pP), with minor (miD), intermediate (inD) and major (maD) deviations. In order to exclude biases through patients who discontinued treatment, patients who received ≥60 Gy were additionally analysed. ResultsBetween 05/2009–11/2016, 205 patients were randomized, 204 patients started treatment according to protocol of which 31 (15%) patients had maD. Patients with maD had an inferior overall survival (OS) (HR 2.9, 95% CI 1.8–4.4, p < 0.0001) and a higher risk of loco-regional progression (HR 5.7, 95% CI 2.7–11.1, p < 0.0001). These results were significant also in the subgroup of patients receiving ≥ 60 Gy. Patients with maD concerning normal tissue delineation and/or dose constraints had a worse OS (p = 0.006) although no higher incidence of grade ≥ 3 toxicities. ConclusionsNon-adherence to the radiotherapy protocol was associated with an inferior OS and loco-regional control. These results underline the importance of RTQA.

Palliative Thoracic Radiotherapy for Non-small Cell Lung Cancer: Is There any Impact of Target Volume Size on Survival?

Recent studies suggested that target volume size impacts survival in patients with non-small cell lung cancer (NSCLC) receiving radical radiotherapy. Little is known about the impact of target volume size in palliative radiotherapy or chemoradiotherapy. Therefore, we analyzed the overall survival stratified for clinical and planning target volume (CTV and PTV) size. A retrospective study of 77 patients who received palliative (chemo)radiotherapy (at least 30 Gy) for non-metastatic NSCLC, largely stage III was performed. Typical radiation doses were 10-13 fractions of 3 Gy and 15 fractions of 2.8 Gy. Median survival was 12 months (2-year rate 18%). Three prognostic factors emerged in the multivariate analysis. Hospitalization in the last 4 weeks before radiotherapy increased the hazard of death by a factor of 2.8 (p=0.002). Presence of a T1 or 2 tumor decreased the hazard of death by a factor of 0.5 (p=0.03). Concomitant chemoradiotherapy decreased the hazard of death by a factor of 0.4 (p=0.003). Target volume size was not significantly associated with survival, suggesting that large size should not preclude palliative (chemo)radiotherapy as long as normal tissue dose constraints can be met.

Hypofractionated Prostate Radiation Therapy: Adoption and Dosimetric Adherence Through Clinical Pathways in an Integrated Oncology Network.

Updates to consensus guidelines in October 2018 recommending moderately hypofractionated external beam radiotherapy (mHF-EBRT) in prostate cancer lagged several years after publication of evidence supporting its efficacy. In January 2018, we amended our prostate cancer clinical pathway (CP) to facilitate adoption of mHF-EBRT. Herein, we analyze patterns of care and changes in mHF-EBRT use after the CP modification. Our prostate CP was amended in January 2018 to make mHF-EBRT the recommended treatment for patients with low- and intermediate-risk prostate cancer pursuing curative EBRT monotherapy. Normal-tissue dose constraints accompanied the CP modification to guide planning. Use of mHF-EBRT from 2015 to 2017 was compared with use in 2018 after the CP modification, using the Cochran-Armitage test for trend. Predictors of mHF-EBRT use and adherence to dose constraints were analyzed with binary logistic regression. In 560 patients treated with EBRT monotherapy, mHF-EBRT use increased from 3.7% in 2015-2017 to 85.6% in 2018 (P < .001), whereas conventionally fractionated EBRT (CF-EBRT) use decreased from 96.3% to 14.4% (P < .001). Consultation year of 2018 (odds ratio [OR], 214.6; 95% CI, 94.5 to 484.6; P < .001), treatment at an academic facility (OR, 4.5; 95% CI, 1.8 to 11.3; P = 0.001), and having a smaller prostate (OR, 0.99; 95% CI, 0.97 to 1.00; P = .028) predicted for mHF-EBRT use. At least five of six recommended bladder and rectal dose constraints were met in 89.4% of patients. Modification of our prostate cancer CP, in concert with institutional policies to monitor and audit CP compliance, facilitated rapid adoption of mHF-EBRT in our large, integrated cancer center with good adherence to dosimetric constraints.

Normal Tissue Dose Constraints for Multiple Lung Stereotactic Radiotherapy Treatments

Introduction: The role and use of stereotactic radiotherapy (SABR) is evolving rapidly. A key article by Hanna et al. (2017) provides an excellent overview of current evidence and suggestion of sensible dose constraints. Given the topical nature of this discussion we present a short retrospective analysis of treating multiple lung SABR patients at our centre. Method: We retrospectively analysed toxicity, both early (within 3 months of SABR) and late, and normal tissue dose constraints on all patients who had multiple lung lesions treated with SABR (using volumetric modulated arc therapy (VMAT) technique) at our tertiary centre over a 25-month period from April 2016 until May 2018. Results: We have treated 78 lung lesions in 37 patients with a combination of synchronous lung cancer primaries and lung metastases diagnoses. Median follow-up was 9 months. Almost all patients received treatment on the same day for multiple lesions. We report no grade 3 toxicities in any patient nor any unexpected side effects. 5 patients (14.7%) developed grade 2 pneumonitis. In all 5 patients, lung V12.5 was &gt;20% (range 20.8-32.2%), yet only 1 patient exceeded acceptable lung V20 constraints. Regarding long-term toxicity, 66.6% of patients reported no treatment-related effects. Of 9 patients with long-term toxicity, 8 exceeded V12.5 constraint of &lt;15%, indeed of these 5 were &gt;20%. Lung V20 levels were acceptable for the majority of these. Local control of treated lesions at median follow-up in all comers was 86.2%. Discussion: Our findings show that multiple lung SABR is tolerable, safe with minimal long-term toxicity and acceptable early toxicity. Defining normal lung V12.5 of &lt;15% (optimal) and &lt;20% (acceptable) will significantly reduce the risk of pneumonitis and longer-term toxicity, proving itself more predictive than lung V20 levels for toxicity. Additionally, treating multiple lesions concurrently appears to bare no extra risk to patients.

Assessment of the alpha/beta ratio of the optic pathway to adjust hypofractionated stereotactic radiosurgery regimens for perioptic lesions

Hypofractionation has been recently considered as an alternative to improve stereotactic radiosurgery treatments of lesions close to the optic pathways. To estimate the intrinsic benefit from fractionation versus single-dose radiosurgery for perioptic lesions, the value of the alpha/beta ratio of the optic pathways needs to be known. Based on the linear quadratic (LQ) model, hypofractionation versus single-fraction SRS can be justified in cases where parts of the optic apparatus necessarily receive the full therapeutic peripheral dose, if there is a positive difference between α/s of the lesion and the α/s of the surrounding organs at risk. Furthermore, the knowledge of α/s ratios is required to calculate radiobiological dose parameters, such as the biologically effective dose (BED) and single fraction equivalent dose (SFED), and helps estimate normal tissue complication probability (NTCP), dose constraints, and retreatment doses. Only 3 alpha/beta ratios for the visual system have been published so far, varying between -0.6 and 3.06 Gy. The alpha/beta ratio of the optic pathways was estimated from a fraction equivalent plot based on a meta-analysis of 429 studies published between 2000 and June 2018. We included 15 studies with fraction sizes between 1 and 31, considering the following inclusion criteria: at least one well-documented RION case with detailed dosimetric analysis for the visual system, follow-up period (FUP) of at least 24 months, no tumor progression, no prior radiation. Additionally, we included results from our center on 68 hypofractionated treatments and 161 single-fraction SRS treatments for perioptic lesions. The fraction equivalent (FE) plot method revealed an alpha/beta ratio of the optic pathway of 1.03 Gy, confidence interval [-0.38–1.60]. Well-documented RION cases are rare in the literature; there is still not enough data to distinguish between alpha/beta ratios of the optic chiasm, the nerves, and the tracts. Optimized hypofractionation schedules were calculated for the treatment of meningiomas, chordomas, and brain metastases. Compared to single-fraction SRS, a significant intrinsic benefit from hypofractionation can be achieved, not only for perioptic malignant tumors, but for benign lesions as well, because of the very low alpha/beta ratio of the optic system of 1.03 Gy. An increased single fraction equivalent dose of up to 10% for perioptic meningiomas and of more than 25% for malignant tumors can be reached with optimized hypofractionated stereotactic radiosurgery schedules.

Applying Non-Homogeneous Dose Optimization to Improve Conventionally Fractionated Radiation Plan Quality in Patients with Non-Small Cell Lung Cancer

PurposeNonhomogeneous dose optimization (NHDO) is exploited in stereotactic body radiation therapy (SBRT) to increase dose delivery to the tumor and allow rapid dose falloff to surrounding normal tissues. We investigate changes in plan quality when NHDO is applied to inverse-planned conventionally fractionated radiation therapy (CF-RT) plans in patients with non-small cell lung cancer. Methods and MaterialsPatients with near-central non-small cell lung cancer treated with CF-RT in 2018 at a single institution were identified. CF-RT plans were replanned using NHDO techniques, including normalizing to a lower isodose line, while maintaining clinically acceptable normal tissue constraints and target coverage. Tumor control probabilities were calculated. We compared delivered CF-RT plans using homogenous dose optimization (HDO) versus NHDO using Wilcoxon signed-rank tests. Median values are reported. ResultsThirteen patients were replanned with NHDO techniques. Planning target volume coverage by the prescription dose was similar (NHDO = 96% vs HDO = 97%, P = .3). All normal-tissue dose constraints were met. NHDO plans were prescribed to a lower-prescription isodose line compared with HDO plans (85% vs 97%, P = .001). NHDO increased mean dose to the planning target volume (73 Gy vs 67 Gy), dose heterogeneity, and dose falloff gradient (P < .03). NHDO decreased mean dose to surrounding lungs, esophagus, and heart (relative reduction of 6%, 14%, and 15%, respectively; P < .05). Other normal tissue objectives improved with NHDO, including total lung V40 and V60, heart V30, and maximum esophageal dose (P < .05). Tumor control probabilities doubled from 31.6% to 65.4% with NHDO (P = .001). ConclusionsIn select patients, NHDO principles used in SBRT optimization can be applied to CF-RT. NHDO results in increased tumor dose, reduction in select organ-at-risk dose objectives, and better maintenance of target coverage and normal-tissue constraints compared with HDO. Our data demonstrate that principles of NHDO used in SBRT can also improve plan quality in CF-RT.

Hypofractionated radiotherapy in nine dogs with unresectable solitary lung adenocarcinoma.

Although lung lobectomy is the most common treatment option for dogs with solitary lung tumors, surgery often cannot be performed at the time of diagnosis. In this retrospective, case series study, we described the effects of hypofractionated radiotherapy for tumor mass reduction in nine dogs with solitary lung adenocarcinoma that were later considered for surgical resection, and we assessed the tolerability of the radiation protocol. Tumors were deemed unresectable by the attending veterinarian. The dose prescription was 7.0-12.0Gy/fraction in four to seven fractions, administered weekly for a total dose of 40-50Gy. Treatment planning prioritized normal tissue dose constraints. The median interval between the last radiotherapy session and maximum tumor size reduction was 56 (range: 26-196) days, with six and three dogs exhibiting a partial response and stable disease, respectively. Although acute and late radiation-induced toxicity to the skin and/or lungs developed in all nine dogs, it was self-limiting or improved with short-term anti-inflammatory treatment. Tumor progression after initial size reduction was confirmed in three dogs at 62, 126, and 175 days, respectively, after the last radiotherapy session. Seven of the nine dogs underwent lobectomy a median of 68 days after radiotherapy when tumors were in partial response or stable disease or at the time of progression, and five received systemic chemotherapy concurrent with or after radiotherapy. These findings suggest that hypofractionated radiotherapy for canine solitary lung adenocarcinoma is useful when the tumor is large or when surgery cannot be performed immediately after diagnosis.

Hypofractionated Radiation Therapy for Localized Prostate Cancer: Executive Summary of an ASTRO, ASCO and AUA Evidence-Based Guideline.

The aim of this guideline is to present recommendations regarding moderately hypofractionated (240-340 cGy per fraction) and ultrahypofractionated (500 cGy or more per fraction) radiation therapy for localized prostate cancer. The American Society for Radiation Oncology convened a task force to address 8 key questions on appropriate indications and dose-fractionation for moderately and ultrahypofractionated radiation therapy, as well as technical issues, including normal tissue dose constraints, treatment volumes, and use of image guided and intensity modulated radiation therapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and Society-approved tools for grading evidence quality and recommendation strength. Based on high-quality evidence, strong consensus was reached for offering moderate hypofractionation across risk groups to patients choosing external beam radiation therapy. The task force conditionally recommends ultrahypofractionated radiation may be offered for low- and intermediate-risk prostate cancer but strongly encourages treatment of intermediate-risk patients on a clinical trial or multi-institutional registry. For high-risk patients, the task force conditionally recommends against routine use of ultrahypofractionated external beam radiation therapy. With any hypofractionated approach, the task force strongly recommends image guided radiation therapy and avoidance of nonmodulated 3-dimensional conformal techniques. Hypofractionated radiation therapy provides important potential advantages in cost and convenience for patients, and these recommendations are intended to provide guidance on moderate hypofractionation and ultrahypofractionation for localized prostate cancer. The limits in the current evidentiary base-especially for ultrahypofractionation-highlight the imperative to support large-scale randomized clinical trials and underscore the importance of shared decision making between clinicians and patients.

Hypofractionated Radiation Therapy for Localized Prostate Cancer: Executive Summary of an ASTRO, ASCO, and AUA Evidence-Based Guideline

PurposeThe aim of this guideline is to present recommendations regarding moderately hypofractionated (240-340 cGy per fraction) and ultrahypofractionated (500 cGy or more per fraction) radiation therapy for localized prostate cancer. Methods and MaterialsThe American Society for Radiation Oncology convened a task force to address 8 key questions on appropriate indications and dose-fractionation for moderately and ultrahypofractionated radiation therapy, as well as technical issues, including normal tissue dose constraints, treatment volumes, and use of image guided and intensity modulated radiation therapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and Society-approved tools for grading evidence quality and recommendation strength. ResultsBased on high-quality evidence, strong consensus was reached for offering moderate hypofractionation across risk groups to patients choosing external beam radiation therapy. The task force conditionally recommends ultrahypofractionated radiation may be offered for low- and intermediate-risk prostate cancer but strongly encourages treatment of intermediate-risk patients on a clinical trial or multi-institutional registry. For high-risk patients, the task force conditionally recommends against routine use of ultrahypofractionated external beam radiation therapy. With any hypofractionated approach, the task force strongly recommends image guided radiation therapy and avoidance of nonmodulated 3-dimensional conformal techniques. ConclusionsHypofractionated radiation therapy provides important potential advantages in cost and convenience for patients, and these recommendations are intended to provide guidance on moderate hypofractionation and ultrahypofractionation for localized prostate cancer. The limits in the current evidentiary base—especially for ultrahypofractionation—highlight the imperative to support large-scale randomized clinical trials and underscore the importance of shared decision making between clinicians and patients.