Intensity Modulated Radiation Therapy Cohort Research Articles

Radiation-Induced Lymphopenia is a Causal Mediator of Survival After Chemoradiotherapy for Esophagus Cancer

Purpose: Radiation-induced lymphopenia (RIL) is common during chemoradiotherapy. Severe lymphopenia is associated with reduced survival. Proton beam therapy (PBT), with its substantially more compact dose distributions, spares circulating lymphocytes and immuno-organs at risk to a greater extent than does photon therapy. Recent studies comparing PBT to photon radiotherapy, specifically intensity-modulated radiation therapy (IMRT), for esophageal cancer (EC) showed that the incidence of grade 4 RIL (G4RIL) is significantly reduced among patients receiving PBT for esophageal cancer. However, whether the extent of this reduction has a direct causative link with improved survival is unknown. This study applies causal mediation analysis to answer this question. Methods and Materials: We retrospectively assessed 734 patients treated with concurrent chemoradiotherapy for biopsy-proven EC from 2004 through 2017. To address the potential for bias in the choice of radiation modality, propensity score analysis was used to evaluate and reduce imbalances between the PBT and IMRT cohorts. Causal mediation analysis was applied to decompose the total effect of radiation modality on overall survival (OS) into indirect (mediated through G4RIL) and direct effects. Results: We found that PBT was associated with significantly lower incidence of G4RIL and prolonged OS compared with IMRT (odds ratio [OR]= 0.41, 95% confidence interval [CI] 0.28 to 0.60, P<0.001). In the propensity-matched cohort of 506 patients (253 PBT, 253 IMRT), G4RIL risk reduction with PBT vs. IMRT translated into a 5% reduction in the relative rate of death (P=0.032). Mediation of G4RIL explained ∼14.5% of the difference in OS. Conclusions: G4RIL was found to mediate survival; however, statistically significant direct effect of PBT on survival was not observed. In other words, the survival benefit from protons over photons in this EC cohort was lost in the absence of G4RIL risk reduction.

A pooled patient-reported outcomes analysis of moderately hypofractionated proton beam therapy and photon-based intensity modulated radiation therapy for low- or intermediate-risk prostate cancer.

We sought to characterize and compare late patient-reported outcomes (PROs) after moderately hypofractionated intensity modulated radiation therapy (IMRT) and proton beam therapy (PBT) for localized prostate cancer (PC). This multi-institutional analysis included low- or intermediate-risk group PC patients treated with moderately hypofractionated radiation to an intact prostate stratified by treatment modality: IMRT or PBT. The primary outcomes were prospectively collected patient-reported late gastrointestinal (GI) and genitourinary (GU) toxicity assessed by International Prostate Symptom Score (IPSS) and Expanded PC Index Composite (EPIC). Multivariable regression analysis (MVA) controlling for age, race, and risk group tested the effect of time, treatment, and their interaction. 287 IMRT and 485 PBT patients were included. Intermediate risk group (81.2 vs. 68.2%; p < 0.001) and median age at diagnosis (70 vs. 67 years; p < 0.001) were higher in the IMRT group. On MVA, there was no significant difference between modalities. PBT IPSS did not differ from IMRT IPSS at 12 months (odds ratio [OR], 1.19; p = 0.08) or 24 months (OR, 0.99; p = 0.94). PBT EPIC overall GI function at 12 months (OR, 3.68; p = 0.085) and 24 months (OR 2.78; p = 0.26) did not differ from IMRT EPIC overall GI function. At 24 months, urinary frequency was no different between PBT and IMRT groups (OR 0.35; p = 0.096). This multi-institutional analysis of low- or intermediate-risk PC treated with moderately hypofractionated PBT and IMRT demonstrated low rates of late patient-reported GI and GU toxicities. After covariate adjustment, late GI and GU PROs were not significantly different between PBT or IMRT cohorts.

Reduced Risk of Lymphedema With Intensity-modulated Radiation Therapy Compared With 3-dimensional Conformal Radiation Therapy in Patients With Cervical Cancer Who Received Postoperative Pelvic Radiation Therapy.

To compare the long-term adverse events of intensity-modulated radiation therapy (IMRT) with those of 3-dimensional conformal radiation therapy (3D-CRT) in patients with intermediate-risk and high-risk uterine cervical cancer who underwent postoperative pelvic radiation therapy (PORT). We reviewed the medical records of 177 patients with cervical cancer who underwent radical surgery and PORT. IMRT and 3D-CRT were administered to 93 and 84 patients, respectively. Follow-up and toxicity assessments were then carried out. The median follow-up period was 63 months (range: 3 to 177). There was a significant difference in the follow-up period between the IMRT and 3D-CRT cohorts (median: 59 vs. 112mo, P <0.0001). The crude incidences of acute grade 2+ and grade 3+ gastrointestinal toxicities were significantly lower with IMRT than with 3D-CRT (22.6% vs. 48.1%, P =0.002, and 3.2% vs. 11.1%, P =0.04, respectively). The Kaplan-Meier estimates of late toxicities revealed that IMRT significantly reduced grade 2+ genitourinary (GU) toxicity and lower-extremity lymphedema ([LEL] requiring intervention) compared with 3D-CRT ([6.8% vs. 15.2% at 5-year, P =0.048] and [3.1% vs. 14.6% at 5-year, P =0.0029], respectively). IMRT was the only significant predictor of reducing LEL risk. The risks of acute gastrointestinal toxicity, late GU toxicity, and LEL from PORT for cervical cancer were reduced by IMRT. Lower inguinal doses may have contributed to a lower risk of developing LEL, which should be validated in future studies.

Long-term follow up of patients with hematological malignancies treated with total body irradiation using intensity modulated radiation therapy.

With the advent of modern radiation treatment technologies such as intensity modulated radiation therapy (IMRT), there has been increasing interest in its use for total body irradiation (TBI) conditioning regimens for hematopoietic cell transplantation (HCT) to achieve lower doses to critical organs such as the lungs and kidneys. Although this has been reported on in early studies, long-term safety and efficacy data is limited. We performed a single institution matched-pair retrospective analysis of patients treated with IMRT TBI and standard TBI between 2010 and 2020 to provide data on long-term outcomes. Patients with hematologic malignancies, who could not tolerate standing for traditional TBI or who received prior radiation received IMRT TBI. Patients were matched based on age, diagnosis, disease status, and year of transplant, and were matched 2:1 to the standard TBI and IMRT TBI cohorts. Patient and treatment characteristics, toxicity, graft-versus-host disease (GVHD), dosimetry, and outcomes were evaluated for each cohort. A total of 13 patients met inclusion criteria for the IMRT cohort, leading to 26 patients in the standard TBI cohort. There was no significant difference in relevant clinical factors between the cohorts. Reasons for using IMRT over conventional TBI included being unable to stand (n=5), prior radiation (n=5), and pediatric patient requiring anesthesia (n=3). Among living patients, median follow-up for all patients was 5.1 years in the IMRT TBI cohort and 5.5 years in the standard TBI cohort. The 5-yr estimate of OS was 68% in the IMRT TBI cohort and 60% in the standard TBI cohort (p=0.706). The 5-yr estimate of RFS was 54% in the IMRT TBI cohort and 60% in the standard TBI cohort (p=0.529). There was no clinically significant pneumonitis, nephritis, hypothyroidism, or cataracts reported in the IMRT TBI cohort. 41.7% of patients in the IMRT TBI cohort and 79.2% of patients in the standard TBI cohort experienced Grade II-IV acute GVHD (p=0.023). IMRT TBI appears to lead to favorable long-term outcome and dosimetry, and therefore potentially improved long-term toxicity profile compared to conventional TBI. IMRT TBI warrants further investigation as part of larger prospective trials.

Heterogeneous Versus Homogeneous Radiation Dose Calculations of Twice-Daily Fractionation in Small Cell Lung Carcinoma.

PurposeThe standard radiotherapy regimen for small cell lung cancer (SCLC) was determined using dose calculations without corrections for tissue heterogeneity, while modern treatments are planned using algorithms accounting for tissue heterogeneity. We assessed differences in dose delivered using heterogeneous and homogeneous dose calculations in a cohort of patients treated for limited-stage small cell lung cancer (LS-SCLC).MethodsThis is a retrospective analysis of 35 patients (three-dimensional conformal radiation therapy (3D-CRT), n = 22; intensity-modulated radiation therapy (IMRT), n = 13) with LS-SCLC treated with chemoradiotherapy from 2011 to 2017. Treatment plans were developed in the Eclipse Treatment Planning System (TPS) version 13.6 using the Analytical Anisotropic Algorithm (AAA). Two plans were generated for each patient with one using the unit relative electron density and the other maintaining the same monitor units (MUs) with tissue density corrections. The prescription was 45 Gy in 30 fractions of 1.5 Gy delivered twice daily. Individuals who underwent replanning within the same treatment course were evaluated using a separate corrected and uncorrected plan sum. Variations greater than 5% in dose to the tumor or organs at risk were considered clinically relevant. A two-sided paired t-test was used to evaluate the statistical significance of the dosimetric differences.ResultsThe percent dose difference between plans without tissue heterogeneity corrections to those with corrections resulted in an overall median difference of -3% (range: -15.1% to 9.6%; p < 0.01) for the dose covering 95% of the planning target volume (PTV D95) and was -5.6% (range: -17.3% to 5.4%; p < 0.01) for lung volume receiving ≥20 Gy (lung V20). For 3D-CRT, the median difference for the PTV D95 was -0.1% (range: -4.7% to 9.6%; p = 0.62) and the lung V20 was -4.2% (range: -9.4 to 5.4; p < 0.01). For IMRT, the median difference for the PTV D95 was -10.0% (range: -15.1% to -5.3%; p < 0.01) and the lung V20 was -8.9% (range: -17.3 to -3.5; p < 0.01).ConclusionTraditional planning without tissue heterogeneity corrections results in an overall decrease in the dose delivered to the target compared with those that incorporate tissue heterogeneity corrections. These differences are modest for 3D treatment plans but may result in clinically relevant differences for the IMRT cohort (>5% deviation).

Dosimetric Predictors of Toxicity in Patients With Early-Stage Prostate Cancer Treated With Moderately Hypofractionated IMRT or PBT: A Multi-Institutional Analysis

<h3>Purpose/Objective(s)</h3> Limited published data address modifiable risk factors for significant toxicity complicating moderately hypofractionated schedules of intensity-modulated radiation therapy (IMRT) and proton-beam therapy (PBT) in patients with early-stage prostate cancer (PC). This study explored dosimetric predictors of Grade 3+ gastrointestinal (GI) and genitourinary (GU) toxicity following IMRT or PBT in this patient population. <h3>Materials/Methods</h3> The study population included patients from five tertiary referral centers treated from 2002-2018 for low- or intermediate-risk biopsy-proven prostate adenocarcinoma. All patients were treated with moderately hypofractionated radiation defined as 250–300 cGY per daily fraction given over 4-6 weeks. Primary outcomes were late GI and GU toxicity as defined by CTCAE v4.0. Dosimetric variables included PTV max dose, PTV volume, bladder V31 Gy, bladder V50 Gy, bladder V70 Gy, bladder max dose, rectum V31 Gy, rectum V50 Gy, rectum V70 Gy, rectum max dose, penile bulb V10 Gy, penile bulb V15 Gy, and the left and right femoral head V40 Gy. The association of dosimetric variables with treatment toxicity was assessed with the Wilcoxon signed-rank test. <h3>Results</h3> Dosimetric data were obtained for 1139 patients, including 667 treated with IMRT and 472 treated with PBT. Median follow-up for the two groups was 46.0 and 48.5 months, respectively. Late toxicity rates for the total population were 4.7% for Grade 3+ GU toxicity and 1.5% for Grade 3+ GI toxicity. Grade 3+ GU toxicity was associated with prostate volume, bladder V31 Gy and bladder V50 Gy (<i>P</i> = 0.016, <i>P</i> = 0.018, <i>P</i> = 0.028), but not with bladder V70 Gy or maximum dose to the bladder. Grade 3+ GI toxicity was not associated with any of the dosimetric variables. When analyzed by treatment group, Grade 3+ GU toxicity was observed in 3% of the IMRT cohort and 1.7% of the PBT cohort. Grade 3+ GI toxicity was seen only in PBT and was observed in 1.5% of patients. Proton plans were associated with less radiation exposure of rectum and bladder at lower doses (rectum V31 Gy: 13% vs 16%, <i>P</i> < 0.001; bladder V31 Gy: 18% vs 26%, <i>P</i> < 0.001), while IMRT was associated with less radiation exposure of rectum and bladder at higher doses (rectum V70 Gy: 0.4% vs 2%, <i>P</i> < 0.001; bladder V70 Gy: 1% vs 3%, <i>P</i> < 0.001). Photon plans yielded superior V40 Gy to the femoral heads, and superior V10 Gy and V15 Gy to the penile bulb (<i>P</i> < 0.001, <i>P</i> < 0.003, <i>P</i> < 0.002). <h3>Conclusion</h3> In this multi-institutional analysis of 1139 early-stage PC patients treated with moderately hypofractionated IMRT or PBT, risk of serious late GU and GI complications was low for both treatment groups. Analysis of the dosimetric variables identified an association of Grade 3+ GU toxicity with low-dose radiation exposure of the bladder. Grade 3+ GI toxicity was unrelated to dosimetric variables. PBT plans yielded less exposure of non-target organs to lower-dose radiation while IMRT plans yielded less exposure of non-target organs to higher-dose radiation.

IMRT QA and gamma comparisons: The impact of detector geometry, spatial sampling, and delivery technique on gamma comparison sensitivity.

To separately quantify sensitivity differences in patient-specific quality assurance comparisons analyzed with the gamma comparison for different measurement geometries, spatial samplings, and delivery techniques [intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT)]. Error-free calculations for 20 IMRT and 20 VMAT cases were compared to calculations with known induced errors of varying magnitudes, using gamma comparisons. Five error types (MU scaling, three different MLC errors, and collimator errors) were induced in plan calculations on three different detector geometries - ArcCHECK, MapCHECK, and Delta 4. To study detector geometry sensitivity effects alone, gamma comparisons were made with 1mm error-free calculations compared to 1mm error-induced calculations for each device. Effects of spatial sampling were studied by making the same gamma comparisons, but down-sampling the error-induced calculations to the real spatial sampling of each device. Additionally, 1mm vs 1mm comparisons between the IMRT and VMAT cases were compared to investigate sensitivity differences between IMRT and VMAT using IMRT and VMAT cohorts with similar ranges of plan complexity and average aperture size. For each case, induced error type, and device, five different gamma criteria were studied to ensure sensitivity differences between devices, spatial sampling scenarios, and delivery technique were not gamma criterion specific, resulting in over 36,000 gamma comparisons. For IMRT cases, Delta4 and MapCHECK devices had similar error sensitivities for lagging leaf, bank shift, and MU errors, while the ArcCHECK had considerably lower sensitivity than the planar-type devices. For collimator errors and perturbational leaf errors the ArcCHECK had higher error sensitivity than planar-type devices. This behavior was independent of gamma parameters (percent dose difference, distance-to-agreement, and low dose threshold), though use of local normalization resulted in error sensitivites that were markedly similar between all three devices. Differences between detector geometries were less pronounced for VMAT deliveries. Error sensitivity for a given gamma criterion when comparing IMRT and VMAT deliveries on the same devices showed that VMAT plans were more sensitive to some specific error types and less sensitive to others, when compared to IMRT plans. For the ArcCHECK device, the sensitivity of IMRT and VMAT cases was quite similar, whereas this was not the case for the planar-type devices. When comparing error sensitivity between 1mm vs 1mm calculations and 1mm vs the real spatial sampling for each device, results showed that increased spatial sampling did not systematically increase error sensitivity. Noticeable differences in error sensitivity were observed for different detector geometries, but differences were dependent on induced error type, and a particular device geometry did not offer universal improvements in error sensitivity across studied error types. This study demonstrates that the sensitivity of the gamma comparison does not largely hinge on detector spatial sampling. VMAT deliveries were generally less sensitive to errors when compared to IMRT plans for the planar-type devices, while similar sensitivities were observed between delivery techniques for the ArcCHECK device. Results of this work suggest that a universal gamma criterion is inappropriate for IMRT QA and that the percent pixels passing is an insufficient metric for evaluating quality assurance checks in the clinic.

Comparison of multimodal surgical and radiation treatment methods for pediatric craniopharyngioma: long-term analysis of progression-free survival and morbidity.

The authors compared survival and multiple comorbidities in children diagnosed with craniopharyngioma who underwent gross-total resection (GTR) versus subtotal resection (STR) with radiation therapy (RT), either intensity-modulated radiation therapy (IMRT) or proton beam therapy (PBT). The authors hypothesized that there are differences between multimodal treatment methods with respect to morbidity and progression-free survival (PFS). The medical records of children diagnosed with craniopharyngioma and treated surgically between February 1997 and December 2018 at Texas Children's Hospital were reviewed. Surgical treatment was stratified as GTR or STR + RT. RT was further stratified as PBT or IMRT; PBT was stratified as STR + PBT versus cyst decompression (CD) + PBT. The authors used Kaplan-Meier analysis to compare PFS and overall survival, and chi-square analysis to compare rates for hypopituitarism, vision loss, and hypothalamic obesity (HyOb). Sixty-three children were included in the analysis; 49% were female. The mean age was 8.16 years (95% CI 7.08-9.27). Twelve of 14 children in the IMRT cohort underwent CD. The 5-year PFS rates were as follows: 73% for GTR (n = 31), 54% for IMRT (n = 14), 100% for STR + PBT (n = 7), and 77% for CD + PBT (n = 11; p = 0.202). The overall survival rates were similar in all groups. Rates of hypopituitarism (96% GTR vs 75% IMRT vs 100% STR + PBT, 50% CD + PBT; p = 0.023) and diabetes insipidus (DI) (90% GTR vs 61% IMRT vs 85% STR + PBT, 20% CD + PBT; p = 0.004) were significantly higher in the GTR group. There was no significant difference in the HyOb or vision loss at the end of study follow-up among the different groups. Within the PBT group, 2 patients presented a progressive vasculopathy with subsequent strokes. One patient experienced a PBT-induced tumor. GTR and CD + PBT presented similar rates of 5-year PFS. Hypopituitarism and DI rates were higher with GTR, but the rate of HyOb was similar among different treatment modalities. PBT may reduce the burden of hypopituitarism and DI, although radiation carries a risk of potential serious complications, including progressive vasculopathy and secondary malignancy. Further prospective study comparing neurocognitive outcomes is necessary.

A Pooled Toxicity Analysis of Moderately Hypofractionated Proton Beam Therapy and Intensity Modulated Radiation Therapy in Early-Stage Prostate Cancer Patients.

Data comparing moderately hypofractionated intensity modulated radiation therapy (IMRT) and proton beam therapy (PBT) are lacking. We aim to compare late toxicity profiles of patients with early-stage prostate cancer treated with moderately hypofractionated PBT and IMRT. This multi-institutional analysis included patients with low- or intermediate-risk biopsy-proven prostate adenocarcinoma from 7 tertiary referral centers treated from 1998 to 2018. All patients were treated with moderately hypofractionated radiation, defined as 250 to 300 cGy per daily fraction given for 4 to 6 weeks, and stratified by use of IMRT or PBT. Primary outcomes were late genitourinary (GU) and gastrointestinal (GI) toxicity. Adjusted toxicity rates were calculated using inverse probability of treatment weighting, accounting for race, National Comprehensive Cancer Network risk group, age, pretreatment International Prostate Symptom Score (GU only), and anticoagulant use (GI only). A total of 1850 patients were included: 1282 IMRT (median follow-up 80.0 months) and 568 PBT (median follow-up 43.9 months). Overall toxicity rates were low, with the majority of patients experiencing no late GU (56.6%, n = 1048) or late GI (74.4%, n = 1377) toxicity. No difference was seen in the rates of late toxicity between the groups, with late grade 3+ GU toxicity of 2.0% versus 3.9% (odds ratio [OR] 0.47; 95% confidence interval 0.17-1.28) and late grade 2+ GI toxicity of 14.6% versus 4.7% (OR 2.69; confidence interval 0.80-9.05) for the PBT and IMRT cohorts, respectively. On multivariable analysis, no factors were significantly predictive of GU toxicity, and only anticoagulant use was significantly predictive of GI toxicity (OR 1.90; P = .008). In this large, multi-institutional analysis of 1850 patients with early-stage prostate cancer, treatment with moderately hypofractionated IMRT and PBT resulted in low rates of toxicity. No difference was seen in late GI and GU toxicity between the modalities during long-term follow-up. Both treatments are safe and well tolerated.

Radiation-Induced Brachial Plexopathy in Patients With Breast Cancer Treated With Comprehensive Adjuvant Radiation Therapy

PurposeOur purpose was to describe the risk of radiation-induced brachial plexopathy (RIBP) in patients with breast cancer who received comprehensive adjuvant radiation therapy (RT). Methods and MaterialsRecords for 498 patients who received comprehensive adjuvant RT (treatment of any residual breast tissue, the underlying chest wall, and regional nodes) between 2004 and 2012 were retrospectively reviewed. All patients were treated with conventional 3 to 5 field technique (CRT) until 2008, after which intensity modulated RT (IMRT) was introduced. RIBP events were determined by reviewing follow-up documentation from oncologic care providers. Patients with RIBP were matched (1:2) with a control group of patients who received CRT and a group of patients who received IMRT. Dosimetric analyses were performed in these patients to determine whether there were differences in ipsilateral brachial plexus dose distribution between RIBP and control groups. ResultsMedian study follow-up was 88 months for the overall cohort and 92 months for the IMRT cohort. RIBP occurred in 4 CRT patients (1.6%) and 1 IMRT patient (0.4%) (P = .20). All patients with RIBP in the CRT cohort received a posterior axillary boost. Maximum dose to the brachial plexus in RIBP, CRT control, and IMRT control patients had median values of 56.0 Gy (range, 49.7-65.1), 54.8 Gy (47.4-60.5), and 54.8 Gy (54.2-57.3), respectively. ConclusionsRIBP remains a rare complication of comprehensive adjuvant breast radiation and no clear dosimetric predictors for RIBP were identified in this study. The IMRT technique does not appear to adversely affect the development of this late toxicity.

Transoral robotic surgery and intensity-modulated radiotherapy in the treatment of the oropharyngeal carcinoma: a systematic review and meta-analysis.

To perform a meta-analysis evaluating trans-oral robotic surgery (TORS), and intensity-modulated radiation therapy (IMRT) in the treatment of oropharyngeal squamous cell carcinoma (OPSCC). This study adhered to the PRISMA guidelines. A total of 5624 patients (IMRT, n = 4322; TORS, n = 1302) were included in this meta-analysis. The majority of patients in the IMRT cohort were treated with concurrent CT (n = 3433, 81.3%). On the other hand, the majority of patients in the TORS cohort was treated with an adjuvant treatment (n = 826, 67.8%). IMRT subgroup showed a cumulative survival rate of 83.6% (99% CI 76.9-89.3%), while it was 91.3% (99% CI 81.2-97.8%) in the TORS subgroup. Disease-free survival was significantly different between IMRT (79.6%, 99% CI 70.6-87.3%), and TORS (89.4%, 99% CI 82.7-94.5%). IMRT subgroup showed a feeding tube dependence rate of 4.0% (99% CI 1.1-8.4%), but it was not significantly different from the TORS subgroup (1.3%, 99% CI 0-4.9%). Tracheostomy dependence rates were similar among the two subgroups (IMRT, 0.7%, 99% CI 0-1.1%; TORS, 0.2%, 99% CI 0-1.1%). TORS appears to be a consolidated effective surgical approach in the management of OPSCC, according to both oncologic and functional outcomes. Further RCTs comparing TORS and IMRT with homogeneous cohorts in terms of tumor staging and HPV status are advisable.

Scanning Beam Proton Therapy versus Photon IMRT for Stage III Lung Cancer: Comparison of Dosimetry, Toxicity, and Outcomes

PurposeThere are limited clinical data on scanning-beam proton therapy (SPT) in treating locally advanced lung cancer, as most published studies have used passive-scatter technology. There is increasing interest in whether the dosimetric advantages of SPT compared with photon therapy can translate into superior clinical outcomes. We present our experience of SPT and photon intensity modulated radiation therapy (IMRT) with clinical dosimetry and outcomes in patients with stage III lung cancer. Methods and MaterialsPatients with stage III lung cancer treated at our center between 2013 and May 2018 were identified in compliance with our institutional review board (64 patients = 34 SPT + 30 IMRT). Most proton patients were treated with pencil beam scanning (28 of 34), and 6 of 34 were treated with uniform scanning. Fisher exact test, χ2 test, and Mann-Whitney test were used to compare groups. All tests were 2-sided. ResultsPatient characteristics were similar between the IMRT and SPT patients, except for worse lung function in the IMRT group. Mean dose to lung, heart, and esophagus was lower in the SPT group, with most benefit in the low-dose region (lungs, 9.7 Gy vs 15.7 Gy for SPT vs IMRT, respectively [P = .004]; heart, 7 Gy vs 14 Gy [P = .001]; esophagus, 28.2 Gy vs 30.9 Gy [P = .023]). Esophagitis and dermatitis grades were not different between the 2 groups. Grade 2+ pneumonitis was 21% in the SPT group and 40% in the IMRT group (P = .107). Changes in blood counts were not different between the 2 groups. Overall survival and progression-free survival were not different between SPT and IMRT (median overall survival, 41.6 vs 30.7 months, respectively [P = .52]; median progression-free survival, 19.5 vs 14.6 months [P = .50]). ConclusionsWe report our experience with SPT and IMRT in stage III lung cancer. Our cohort of patients treated with SPT had lower doses to normal organs (lungs, heart, esophagus) than our IMRT cohort. There was no statistically significant difference in toxicity rates or survival, although there may have been a trend toward lower rates of pneumonitis.

Scanning Beam Proton Therapy Versus Photon IMRT for Stage III Lung Cancer: Comparison of Dosimetry, Toxicity and Outcomes

Abstract Purpose There are limited clinical data on scanning-beam proton therapy (SPT) in treating locally advanced lung cancer, as most published studies have used passive-scatter technology. There is increasing interest in whether the dosimetric advantages of SPT compared with photon therapy can translate into superior clinical outcomes. We present our experience of SPT and photon intensity modulated radiation therapy (IMRT) with clinical dosimetry and outcomes in patients with stage III lung cancer. Methods and Materials Patients with stage III lung cancer treated at our center between 2013 and May 2018 were identified in compliance with our institutional review board (64 patients = 34 SPT + 30 IMRT). Most proton patients were treated with pencil beam scanning (28 of 34), and 6 of 34 were treated with uniform scanning. Fisher exact test, χ2 test, and Mann-Whitney test were used to compare groups. All tests were 2-sided. Results Patient characteristics were similar between the IMRT and SPT patients, except for worse lung function in the IMRT group. Mean dose to lung, heart, and esophagus was lower in the SPT group, with most benefit in the low-dose region (lungs, 9.7 Gy vs 15.7 Gy for SPT vs IMRT, respectively [P = .004]; heart, 7 Gy vs 14 Gy [P = .001]; esophagus, 28.2 Gy vs 30.9 Gy [P = .023]). Esophagitis and dermatitis grades were not different between the 2 groups. Grade 2+ pneumonitis was 21% in the SPT group and 40% in the IMRT group (P = .107). Changes in blood counts were not different between the 2 groups. Overall survival and progression-free survival were not different between SPT and IMRT (median overall survival, 41.6 vs 30.7 months, respectively [P = .52]; median progression-free survival, 19.5 vs 14.6 months [P = .50]). Conclusions We report our experience with SPT and IMRT in stage III lung cancer. Our cohort of patients treated with SPT had lower doses to normal organs (lungs, heart, esophagus) than our IMRT cohort. There was no statistically significant difference in toxicity rates or survival, although there may have been a trend toward lower rates of pneumonitis.

Dosimetric Analysis of Standard vs. IMRT Pelvic Radiation for Post-Operative Treatment of Endometrial and Cervical Cancer in NRG Oncology’s RTOG 1203

NRG Oncology’s RTOG 1203 demonstrated improved acute toxicity with post-operative intensity modulated radiation therapy (IMRT) for treatment of cervical and endometrial cancer compared to 3D-conformal (3DCRT) techniques. We aimed to correlate dosimetric parameters with patient reported outcomes from RTOG 1203, in hopes to establish dose constraints for patients receiving IMRT for cervical and endometrial cancers. Two different patient reported outcome assessment tools were used in this study, the PRO-CTCAE and the EPIC questionnaires. These assessments were evaluated in the bowel (GI) and urinary (GU) domains including subdomains of bowel bother, bowel function, urinary bother, urinary function, urinary incontinence, and urinary irritation. These assessments were completed at baseline, 5 weeks, 1 year and 3 years after the start of radiotherapy. Pearson and spearman correlation coefficients were used to correlate the radiation doses and volumes with these EPIC and PRO-CTCAE scores, and receiver operator curve (ROC) analyses were used to identify optimal dosimetric cut points for toxicity prediction. The initial radiation doses considered were mean bowel dose, rectum V40, rectum V45, and bladder mean dose, as they have shown to be significant predictors of toxicity in other retrospective analyses. Out of the 279, 129 patients on the IMRT arm had radiation dose data. Of the 129 IMRT patients, 72%, 69%, and 46% completed the PRO-CTCAE assessment at 5 weeks, 1 year and 3 years respectively, while 85%, 75%, and 53% of patients completed the EPIC assessment at 5 weeks, 1 year and 3 years. The median bowel dose, rectal V40, and rectal V45 were not statistically different between patients with and without GI symptoms including abdominal pain, diarrhea, and fecal incontinence at any time point (p>0.055). Similarly, median bladder dose was not associated with worsening GU symptoms, such as urinary function, bother or irritation, at any time point (p>0.13). Preliminary analysis of patient reported outcomes demonstrated no significant association with mean dose to bowel, rectal and bladder dosimetry in the IMRT cohort of RTOG 1203. Ongoing analysis will include investigating lower dose thresholds and their association with acute and late GI and GU patient reported outcomes, and to include patients from the 3DCRT cohort.

Early Outcomes of Patients With Locally Advanced Non-small Cell Lung Cancer Treated With Intensity-Modulated Proton Therapy Versus Intensity-Modulated Radiation Therapy: The Mayo Clinic Experience

PurposeThere are very little data available comparing outcomes of intensity-modulated proton therapy (IMPT) to intensity-modulated radiation therapy (IMRT) in patients with locally advanced NSCLC (LA-NSCLC). MethodsSeventy-nine consecutively treated patients with LA-NSCLC underwent definitive IMPT (n = 33 [42%]) or IMRT (n = 46 [58%]) from 2016 to 2018 at our institution. Survival rates were calculated using the Kaplan-Meier method and compared with the log-rank test. Acute and subacute toxicities were graded based on Common Terminology Criteria for Adverse Events, version 4.03. ResultsMedian follow-up was 10.5 months (range, 1-27) for all surviving patients. Most were stage III (80%), received median radiation therapy (RT) dose of 60 Gy (range, 45-72), and had concurrent chemotherapy (65%). At baseline, the IMPT cohort was older (76 vs 69 years, P < .01), were more likely to be oxygen-dependent (18 vs 2%, P = .02), and more often received reirradiation (27 vs 9%, P = .04) than their IMRT counterparts. At 1 year, the IMPT and IMRT cohorts had similar overall survival (68 vs 65%, P = .87), freedom from distant metastasis (71 vs 68%, P = .58), and freedom from locoregional recurrence (86 vs 69%, P = .11), respectively. On multivariate analyses, poorer pulmonary function and older age were associated with grade +3 toxicities during and 3 months after RT, respectively (both P ≤ .02). Only 5 (15%) IMPT and 4 (9%) IMRT patients experienced grade 3 or 4 toxicities 3 months after RT (P = .47). There was 1 treatment-related death from radiation pneumonitis 6 months after IMRT in a patient with idiopathic pulmonary fibrosis. ConclusionsCompared with IMRT, our early experience suggests that IMPT resulted in similar outcomes in a frailer population of LA-NSCLC who were more often being reirradiated. The role of IMPT remains to be defined prospectively.

A Comparison of Prospectively Collected Genitourinary and Gastrointestinal Toxicities and Dose Volume Histogram in Patients Treated with Intensity-Modulated Radiation Therapy or Non-Intensity-Modulated Post-Operative Radiation Therapy

To compare maximum genitourinary (GU) and gastrointestinal (GI) toxicities within 5 weeks of starting radiation therapy between intensity-modulated radiation therapy (IMRT) and conventional radiation therapy (non-IMRT) in post-hysterectomy patients treated for cervical or endometrial cancer. We also were interested to determine the dose volume histogram (DVH) values that predict grade 2+ toxicities. Post-hysterectomy cervical and endometrial cancer patients treated at our institution were retrospectively analyzed for toxicity. GU and GI toxicities were collected prospectively using CTCAE version 4.0 during weekly on-treatment visits using a centralized database from week 1 to 6 of radiation therapy. DVH parameters were analyzed. Univariate analysis of toxicity, patient characteristics, and DVH parameters was performed using chi-square test and logistic regression. A total of 105 post-hysterectomy patients with stages I-IIIC2 endometrial (n=83, 79%) or IA-IIA cervical (n=22, 21%) cancer were treated from May 2003-November 2016. Ninety-one patients (87%) had on treatment visit assessments to evaluate (51 with IMRT and 40 with non-IMRT), including 55 patients (30 with IMRT and 25 with non-IMRT) with DVH parameters available. There was no difference between the two groups regarding baseline patient characteristics. Within 5 weeks of treatment, 23.5% patients in IMRT and 40% in non-IMRT had at least one grade 2+ toxicity (p=0.12). Bowel V40 and V45 were lower in the IMRT (median [Q1-Q3] 216cc [145-373]) than non IMRT (570cc [334-668]) cohorts. Among all patients, bowel V25, V30, V40 and V45 were all significantly associated with increased incidences of any grade 2+ toxicity, while bowel V5, V10, V15, V20 and V35 were not (Table 1). The medians (Q1-Q3) of bowel V45 were 199cc (80-457cc) among those had < grade 2 GI toxicity and 527cc (147-829cc) among those had 2+ GI toxicity (p=0.03).Abstract TU_20_3522: Table 1DVH Parameters and ToxicityBowel DVH: Median cc (Q1-Q3cc)< Grade 2 ToxicityGrade 2+ ToxicityP ValueV51066 (654-1517)1200 (826-1615)0.5V10907 (588-1392)1108 (780-1565)0.36V15814 (537-1160)1037 (680-1499)0.2V20745 (475-1102)1004 (508-1393)0.1V25605 (408-897)905 (395-1270)0.038V30466 (327-727)788 (258-1075)0.027V35398 (271-615)681 (214-966)0.4V40289 (177-472)607 (189-887)0.009V45184 (78-388)527 (155-800)0.005 Open table in a new tab The rates of experiencing at least one grade 2 or higher toxicity were lower for patients treated with IMRT than non-IMRT. Bowel V45 was associated with Grade 2+ toxicity. IMRT was associated with a lower bowel V40 and V45 in this group of post hysterectomy patients.

Preoperative IMRT for soft-tissue sarcoma of the extremities and trunk: low rate of wound complications

Background: The Canadian prospective randomized NCIC SR2 trial tested the sequence of radiation and surgery for extremity soft-tissue sarcoma. The trial was conducted in the era before intensity-modulated radiation therapy (IMRT) was clinically available. Similar disease control after preoperative and postoperative non-IMRT was found. However, the preoperative non-IMRT arm showed significantly less (persisting) late-term effects but increased (transient) wound complication rates compared to the postoperative non-IMRT arm (35% vs. 17%, P = 0.01). Consequently based on these results, preoperative radiation therapy was considered the preferred approach. Currently IMRT, with its option for highly conformal dose distribution that translates into better normal tissue sparing, is used as the general standard for sarcoma radiation therapy in most patients. Our hypothesis was that a lower wound complication rate after preoperative radiation therapy might be achievable in the IMRT era. Methods: We prospectively assessed our preoperative IMRT cohort (n=67 consecutive patients) treated between March 2008 and March 2016 with respect to wound complication rates. Results: Fourteen of 67 (21%) externally referred patients with recurrent (n=1) or incompletely resected disease (n=13), and 53 treatment-naive patients underwent planned preoperative radiation after core biopsy. After mean/median 7.3/7 wk (3-12 wk), complete tumor resection was performed. Secondary revision was required in five of 67 (i.e., wound complication rate of 7%). Two local failures were observed so far. Conclusions: The presented results support our hypothesis that preoperative IMRT may lead to a reduced wound complication rate compared to that after postoperative and mainly preoperative non-IMRT techniques.

Comparison of clinical outcomes with IMRT and proton therapy for prostate cancer.

e16555 Background: The ProtecT trial underscores the importance of treatment in men with prostate cancer and life expectancies &gt; 10 years and the validity of radiation therapy (RT). RT can be given with photons or protons (PT). To address the controversy of which is better, clinical outcomes of photon-based intensity modulated RT (IMRT) and PT cohorts from 2 institutions were directly compared. Methods: Under respective IRB approvals, data from 2 cohorts were analyzed. The first was 301 men treated with ultrasound image guided IMRT from 2000-05 to 75.6 Gy in 42 fractions. The second was 1214 men treated with fiducial image guided PT from 2006-10 to 78 CGE in 39 fractions. Median age and followup were 74 y and 7.2 y for IMRT and 66 y and 5.6 y for PT. Hormone therapy (ADT) was used with IMRT and PT, respectively, in 3% and 7% of low-risk patients, 25% and 9.9% of intermediate-risk, and 91% and 57.8% of high-risk. Comparative endpoints were age-stratified 5-year (5Y) survival (OS), ≥ grade 3 gastrointestinal (GI) and urologic (GU) toxicity, and 5Y freedom from biochemical progression (FFBP). Results: There was a lower prevalence of GI (1.3% vs 0.1%, p = 0.0065) and GU (4.3% vs 0.1%, p &lt; 0.0001) toxicity at last follow-up in the PT group. In the IMRT and PT cohorts, OS rates were 90.8% and 88.7% in men ≥75 (p = 0.4083). In men &lt; 75, OS rates were 91.6% and 97.5% in the IMRT and PT low-risk patients (p = 0.003), 92.1% and 95.5% in the IMRT and PT intermediate-risk (p = 0.0535), and 92.0% and 90.0% (p = 0.4975) in the IMRT and PT high-risk. In the IMRT and PT cohorts, respectively, FFBP rates were 92.2% and 98.9% for low-risk patients (p &lt; 0.0001), 87.3% and 94.5% for intermediate-risk patients(p = 0.0226), and 80.3% and 74.4% for high-risk patients (p = 0.5154). Conclusions: In this retrospective comparison of outcomes in cohorts of men treated with IMRT and PT for prostate cancer, FFBP rates were better with PT for men with low- and intermediate-risk disease and similar in men with high-risk disease despite longer and more frequent use of ADT in the IMRT cohort. This study underscores the difficulty of comparing retrospective series, with differences noted in age, RT dose, and ADT use between cohorts. However, the magnitude of improvement with PT is intriguing and warrants prospective testing.

Sociodemographic disparities in the utilization of proton therapy for prostate cancer at an urban academic center

PurposeDespite increasing use, proton therapy (PT) remains a relatively limited resource. The purpose of this study was to assess clinical and demographic differences in PT use for prostate cancer compared to intensity modulated radiation therapy (IMRT) at a single institution. Methods and materialsAll patients with low- and intermediate-risk prostate cancer (N = 633) who underwent definitive radiation therapy between 2010 and 2015 were divided into PT (n = 508) and IMRT (n = 125) comparison groups and compared using χ2 and independent sample t tests. Univariable and multivariable logistic regression analyses were conducted to assess the associations between PT use and demographic, clinical, and treatment characteristics. ResultsThe PT and IMRT cohorts varied by age, race, poverty, distance, treatment year, and treating physician. Patients who underwent IMRT were more likely to be older (mean age, 66 vs. 68 years), black (51% vs. 75%), and living in poverty or close to the facility (mean distance between residence and facility, 90 vs. 21 miles; P < .05). Prostate-specific antigen, prostate volume, and International Index of Erectile Function were significantly higher in the IMRT cohort (P < .05), but insurance type, risk group, tumor stage, Gleason score, and patient-reported urinary and bowel scores did not differ significantly (P > .05). Patients who underwent PT were more likely to receive hypofractionated therapy and less likely to receive androgen deprivation therapy (P < .01). On multivariable analysis, black (odds ratio [OR], 0.29; 95% confidence interval [CI], 0.15-0.57) and other race (OR, 0.42; 95% CI, 0.20-0.90); distance (OR, 1.14; 95% CI, 1.06-1.24); treatment years 2011 (OR, 4.87; 95% CI, 2.23-10.6), 2012 (OR, 8.27; 95% CI, 3.43-19.9), and 2014 (OR, 4.44; 95% CI, 1.94-10.2) relative to 2010; and a single treating physician (OR, 0.38; 95% CI, 0.18-0.81) relative to the reference physician with the highest rate of use were associated with PT use, whereas clinical factors such as prostate-specific antigen, prostate volume, International Index of Erectile Function, and androgen deprivation therapy were not. ConclusionSociodemographic disparities exist in PT use for prostate cancer at an urban academic institution. Further investigation of potential barriers to access is warranted to ensure equitable distribution across all demographic groups.

The Impact of Intensity Modulated Radiation Therapy on Hospitalization Outcomes in the SEER-Medicare Population With Anal Squamous Cell Carcinoma

We examined the impact of intensity modulated radiation therapy (IMRT) on hospitalization rates in the Surveillance, Epidemiology, and End Results (SEER)-Medicare population with anal squamous cell carcinoma (SCC). We performed a retrospective cohort study using the SEER-Medicare database. We identified patients with nonmetastatic anal SCC diagnosed between 2001 and 2011 and treated with chemoradiation therapy. We assessed the relation between IMRT and first hospitalization by use of a multivariate competing-risk model, as well as instrumental variable analysis, using provider IMRT affinity as our instrument. Of the 1165 patients included in our study, 458 (39%) received IMRT. IMRT use increased over time and was associated more with regional and provider characteristics than with patient characteristics. The 3- and 6-month cumulative incidences of first hospitalization were 41.9% (95% confidence interval [CI], 37.3%-46.4%) and 47.6% (95% CI, 43.0%-52.2%), respectively, for the IMRT cohort and 46.7% (95% CI, 43.0%-50.4%) and 52.1% (95% CI, 48.4%-55.7%), respectively, for the non-IMRT cohort.IMRT was associated with a decreased hazard of first hospitalization compared with 3-dimensional radiation techniques (hazard ratio, 0.70; 95% CI, 0.58-0.84; P=.0002).Instrumental variable analysis suggested an even greater reduction in hospitalizations with IMRT after controlling for unmeasured confounders. There was a trend toward improved overall survival with IMRT, with an adjusted hazard ratio of 0.77 (95% CI, 0.59-1.00; P=.05). The use of IMRT is associated with reduced hospitalizations in elderly patients with anal SCC. Further work is warranted to understand the long-term health and cost impact of IMRT, particularly for patient subgroups most at risk of toxicity and hospitalization.